The essentials

* Most problems arising within the scrotum are benign.

* Carry out emergency surgical exploration in suspected torsion.

* A large tense hydrocoele may mimic an inguinal hernia.

* Any suspicious testicular lesion must be seen urgently by a specialist.

* Varicocoeles can cause poor sperm quality.

1. Causes of scrotal and testicular pain

Many men present with lumps, bumps or pain in the scrotal area. Hernias will also cause swelling in the scrotum. Most problems arising within the scrotum are entirely benign but some conditions, such as tumours or torsion of the testicle, need an accurate diagnosis to be made at initial presentation or require early or immediate referral. It is interesting that scrotal pain is becoming an increasingly common symptom in young men.

Chronic testicular or epididymal pain

In many cases, chronic scrotal discomfort presents in a similar way to prostatic-type pain, with epididymal tenderness in the absence of overt infection.

The condition is commonly found in men who have had previous surgery or who have suffered some sort of trauma to the scrotum. There are no investigations or simple tests that will give a specific diagnosis.

However, an ultrasound scan will help in reassuring the patient that there is no underlying abnormality, since this can allay any anxiety about the possibility of cancer. This is important, because concern about malignancy often plays a part in chronic testicular pain.

Any thickening or fluid collection detected in the epididymis should be further investigated to rule out chronic bacterial inf ection. Tuberculosis is a rare but real possibility that is serious but easily overlooked.

In addition, it is often necessary and appropriate to exclude the presence of an STI or a urinary tract infection. Once these possibilities have been excluded, it is often worthwhile offering treatment with long-term quinolone antibiotics – my recommendation is to use ciprofloxacin for at least three weeks.

However, chronic testicular or epididymal pain can be a difficult condition to treat, and this empirical approach is not always successful. While it is true that physical problems such as epididymal cysts or varicocoeles may cause scrotal pain, it is also the case that in many men the co-existence of a physical abnormality and pain are not linked.

Acute epididymitis

Acute epididymitis tends to present with severe, often bilateral, testicular pain and inflammation that develops over a number of hours or days. In young men the condition is often linked to an STI, particularly with the gonococcus. In older men, a urinary tract infection will more often be the cause.

The differential diagnosis of acute epididymitis is important. This is because in younger men it may be impossible to distinguish the sudden onset of this condition from a testicular torsion. In any case where testicular torsion is suspected, an immediate referral to hospital for a specialist review is needed.

Treatment

The treatment of acute epididymitis is generally doxycycline given for about six days. Alternatively a quinolone antibiotic such as ciprofloxacin can be used, but in this case at least two weeks’ treatment is necessary.

In older men who do not have any risk factors for STI, a broad- spectrum antibiotic may be the best initial course of action. This can be started while awaiting the results of an MSU. Also in the older patient, investigation of possible bladder outflow problems may be appropriate once the initial infection has settled down.

Acute epididymitis causes pain and inflammation

Key points

* Some problems arising within the scrotum such as suspected torsion or tumour require urgent specialist assessment.

* Chronic scrotal discomfort presents with epididymal tenderness in the absence of overt infection.

* There are no investigations or tests that will give a specific diagnosis.

* An ultrasound scan helps exclude any underlying abnormality.

* In younger men it may be impossible to distinguish the sudden onset of acute epididymitis from a testicular torsion.

2. Testicular torsion and Fournier’s gangrene

In some men the testis suffers from hypermobility, with an excess of tissue lying within the sac of the tunica vaginalis. This situation may favour torsion of the testicle.

The classic testicular torsion occurs in a teenage boy with a sudden onset of severe testicular pain associated with abdominal discomfort or nausea. However, this is not exclusively a problem of young men, as the condition may occur in neonates or in men in their forties.

High-resolution Doppler ultrasound may be able to differentiate torsion from acute infection, but it is often impossible to exclude torsion by clinical examination, even when aided by ultrasound. If there is doubt, then emergency surgical exploration should always be carried out.

Avoiding testicular atrophy

To avoid testicular atrophy, timing is critical. Nearly all testicles suffering a torsion that is untwisted and fixed within six hours of the onset of pain will survive. Most of those treated after a delay of 12 hours or more will suffer at least some testicular atrophy.

Both testicles should be fixed at the time of surgery, because the unaffected testicle is also at risk of torsion.

Intermittent torsion may occur, with the patient presenting with typical symptoms, but spontaneously improving before any intervention is carried out. In these cases a decision to operate and permanently fix both testicles is made on clinical grounds.

The testicular appendix

It is possible for the testicular appendix – the hydatid of Morgagni – to tort in children and adolescents, and this presents with acute pain. This small developmental remnant sits just anterior to the head of the epididymis.

A small tender spot may be palpable, and ultrasound can confirm the diagnosis, assuming the boy will let anyone near his tender scrotum. It is a benign and self-limiting condition, but it can be difficult to rule out testicular torsion.

Inflammatory conditions of the testis such as tuberculous, granulomatous or syphilitic orchitis are rarely seen in the UK.

Fournier’s gangrene

This is a necrotising fasciitis involving the genital region and perineum and is due to a mixed aerobic and anaerobic bacteria. Escherichia coli, bacteriodes and clostridia are frequently identified. It may follow a number of events including epididymo- orchitis, perianal abscess or surgery to the area.

Thrombosis of subcutaneous blood vessels occurs, followed by gangrene of the skin. Surgical debridement is invariably required, and orchidectomy results in 10-30 per cent of cases.

Fournier’s gangrene is a form of necrotising fasciitis

Key points

* Hypermobility of the testicle increases the risk of torsion of the testicle.

* Torsion is not exclusively a problem of teenage boys.

* Exploration is needed if in doubt, because clinical examination cannot exclude torsion.

* Testicles suffering from torsions that are untwisted and fixed quickly will survive.

* Torsion of the testicular appendix may occur in children and adolescents and presents with acute pain.

3. Benign lumps and bumps in the scrotum

The diagnostic key to making an accurate diagnosis of testicular lumps and bumps is determining whether the examining fingers can get above the lump. If it is possible to establish that the fingers can reach around and above the swelling, then it is arising from the scrotum. If this is not possible, then it is a hernia.

There is one rare exception to this, and that is sometimes a large tense hydrocoele may mimic an inguinal hernia. An ultrasound is the diagnostic test of choice, and has the added advantage that it may even pick up pre-clinical lesions.

Pilar (sebaceous) cysts occur frequently in the skin of the scrotum, are harmless and usually only need reassurance. Occasionally a request for their removal is made because they cause embarrassment or for cosmetic reasons, especially if they are large.

A much rarer and often unsightly condition is scrotal calcinosis, where multiple calcified nodules occur within the scrotal skin. They are not associated with any abnormality of calcium metabolism.

Epididymal cysts

Swellings of the epididymis are common and will be found in a high percentage of men who have ultrasonography for whatever reason. They may contain serous fluid or spermatozoa.

Most epididymal cysts do not cause pain, but men can become so alarmed on finding them that reassurance may be an essential part of management. Although epididymal cysts may be easily removed, a significant number of men will be left with obstructive azoospermia on the side of the operation, and some patients will develop troublesome post-operative scrotal pain.

As a rule I will not operate on scrotal cysts unless they are of a significant size or the man does not plan to have any more children. If pain is the main problem, this can often be relieved by performing a fine needle aspiration of the cyst.

Hydrocoeles

The normal state is to have potential space around the testis lined by mesothelial cells, with a tiny amount of fluid that allows the testis to move freely. If this fluid increases significantly, a hydrocoele will develop.

This is a different situation to the so-called ‘infantile hydrocoeles’ that still communicate with the peritoneal cavity.

Hydrocoeles \are usually idiopathic, but may arise after trauma, infection or any surgery that affects the lymphatic drainage of the testis or, rarely, a tumour. But if the testis within the hydrocoele causes any concern or is cosmetically unacceptable, then surgery to invert or plicate the sac is a simple matter. The success rate is high and there is no effect on fertility.

Epididymal cysts are common but can cause alarm

Key points

* If the fingers can get above the lump, it arises in the scrotum and is not a hernia.

* An ultrasound is the diagnostic test of choice, and may even pick up pre-clinical lesions.

* Epididymal cysts may be easily removed, but there can be undesirable consequences.

* Hydrocoeles are usually idiopathic, but may arise after trauma, infection or obstruction of the lymphatics.

4. Scrotal and testicular tumours

Most GPs dread missing a testicular tumour in a young man. Urologists realise this, and are happy to see any doubtful cases on an urgent basis. Although testicular cancer is rare overall, it is still the commonest cancer in men under the age of 40.

The classical presentation of testicular cancer is a painless lump in the body of the testis, although some men will notice the lump after an injury or an infection. Most early testicular cancers can be cured by surgery alone, but any delay in diagnosis increases the need for chemotherapy and its intensity.

Types of testicular cancer

Tumours of the testis fall into three groups: nonseminomatous (or teratomas), seminomas and lymphomas. Lymphomas are less common but need to be considered in the elderly.

Until relatively recently there was doubt about the place of ultrasound in the diagnosis of tumours of the testis. Modern high- resolution scanning will give an accurate answer if a man presents with a scrotal lump.

In our institution we have seen a series of men in whom small tumours that are undetectable by the examining physician have been accurately diagnosed by ultrasound. Our research suggests that Doppler ultrasound can tell malignant from benign lesions by their neovascular pattern.

Treatment

Treatment varies depending on the clinical stage and risk factors associated with each tumour. In the UK, radiotherapy to the para- aortic nodes is given to most seminoma patients even without evidence of spread, to reduce the risk of microscopic metastases growing later.

For patients who have organ-confined nonseminoma tumours, either observation or modified platinum-based chemotherapy will be recommended. All patients with metastatic disease are treated with cytotoxic chemotherapy.

Cancers of the epididymis are very rare. Any solid lump detected outside the testis is likely to be inflammatory, but nonetheless must be referred for specialist assessment.

High resolution ultrasound may show small testicular tumours that are undetectable on physical examination

Key points

* Most early testicular cancers can be cured by surgery alone.

* There are three types of testicular tumours: teratomas, seminomas and lymphomas.

* Doppler ultrasound can tell malignant from benign lesions by their neovascular pattern.

* Treatment involves para-aortic radiotherapy.

5. Varicocoeles and other problems

A varicocoele is the only scrotal swelling which does not fit the rule of ‘can you get above it?’

Varicocoeles are much more common on the left side because the testicular vein on the left drains into the renal vein, whereas on the right it goes straight into the vena cava. For reasons that are not clear, the one-way valves in the veins that stop reflux are more likely to become incompetent on the left.

Varicocoeles and poor sperm quality are associated. This is thought to be linked to an abnormally high testicular temperature. Varicocoeles are very common, and seem to occur more often where there is a family history of varicose veins. Although a varicocoele may present in later life in association with a renal tumour, this is rare.

Treatment

Treatment depends on the individual patient. Many Varicocoeles are completely asymptomatic and do not affect a man’s fertility. However, if a man is having discomfort or has a fertility problem, then treatment is justified. Traditionally, open surgery was used but this has a risk of inducing chronic pain.

It is our practice to perform a retrograde transfemoral embolisation, which is a local anaesthetic procedure. On the left side a success rate of some 80 per cent has been achieved.

For bilateral or recurrent varicocoeles, a laparoscopic approach will allow identification of all the abnormal veins at the internal ring, and this procedure can be done as a day case.

Miscellaneous problems

Rarely, infestations such as filariasis may affect the scrotum, causing elephantiasis. Idiopathic scrotal oedema and congestive cardiac failure may also cause scrotal swelling.

Skin cancer is rare in this area, but may affect the scrotal skin. The ‘Pott’s tumour’ seen in chimney sweeps was the first demonstration of environmental carcinogenesis. For obvious reasons, it is much less common now.

Varicocoeles are associated with poor sperm quality

Key points

* Varicocoeles are more common on the left.

* Varicocoele may present in association with a renal tumour, but this is rare.

* Retrograde transfemoral embolisation under local anaesthetic is an effective treatment.

* For bilateral or recurrent varicocoeles, a laparoscopic approach may be best.

Further resources

Further reading

Primary Care Essentials: Urology edited by Daniel K Onion et al, published by Blackwell.

Websites

See Medicine on the Web, page 32.

Previously in Clinical Review

You can produce your own reprints of Clinical Reviews published in the past year by logging on to GPonline.com.

* Audiological medicine (19 August)

* Acute myocardial infarction (12 August)

* ADHD (5 August)

* Penile problems (July 22)

* Travel vaccination (July 15)

Contributed by Mr Gordon Muir, consultant urological surgeon, King’s College Hospital, London, and the Barons Clinic, Reigate, Surrey

Copyright Haymarket Business Publications Ltd. Sep 2, 2005

THE WOMAN sits at her dressing table gazing fixedly at her reflection. Yes, she ponders smugly, she really is holding the years at bay – thanks to all the beauty creams and cosmetic aids arrayed in front of her.

And, honestly, who cares if the ingredients were plundered from the bodies of children, the dead and the poor?

One of her anti-wrinkle gels, for example, contains an ingredient from the foreskin of a circumcised baby.

Her long, lustrous hair – or, to be accurate, hair extensions – ‘belongs’ to a poor Russian child who was forced to sell her locks to survive, and is washed daily in ‘placenta shampoo’ (harvested from a selection of new mothers in the U.S.) to maintain its sheen.

No doubt she has also undergone the latest anti-ageing regime that cells from aborted foetuses. Ah yes, and her lips. They look as if they could belong to a pouting actress, but that is only because they contain skin cells harvested from corpses.

We exaggerate – but not much. The woman described above, of course, probably does not exist. But all these so-called ‘wonder’ products and treatments do – and they are becoming increasingly popular with British women. What a Frankenstein’s Monster the beauty industry has become.

Indeed, behind the creams, gels and potions, the Mail this week uncovered a story that would grace the plot of a sci-fi horror film. And each of these beauty aids is fuelled by the desperation of women whose pursuit of physical perfection and the elixir of eternal youth is both relentless and ruthless.

Cosmetic and pharmaceutical companies as well as doctors are only too happy to meet – some might say exploit – this demand despite the obvious ethical, moral – and potentially, medical – implications.

Only this week, shocking claims emerged that ‘skin’ from executed Chinese criminals were being used in ‘lip and anti-wrinkle’ products sold in Europe.

The revelations were almost too macabre to believe.

The Chinese cosmetics company, which was not named, was said to be providing such treatments at a fraction of the price of rival suppliers after making a secret deal with prison authorities. The skin is alleged to have been taken from inmates after they had been shot. In fact, lip implants – consisting of tissue harvested not from corpses in China but America – are shockingly commonplace in London.

The gruesome chain of events begins at the scene of, say, a fatal road accident or a death, on the other side of the Atlantic and ends in an injection at respected private clinics such as that which trades at 112 Harley Street.

Behind the grand front door of this establishment, stomachs are flattened, creases are ironed out, breasts are enhanced, faces are lifted – and the syringes, containing a substance called AlloDerm, are administered at Pounds 450 a time.

Clients need up to three injections.

But the resulting ‘pout’ is supposed to last for three years.

AlloDerm? It sounds as innocuous as an acne cream. Actually, it is culled from ‘cadavers’ in the U.S. and is essentially freezer- dried human skin minus the epidermis (the outer layer of skin).

It is used – quite legitimately – in hospitals for skin grafts and reconstructive surgery. But it is also used for making your lips look like they belong to a supermodel.

Dr Laurence Kirwan, a eminent and respected plastic surgeon, and one of two doctors who run the clinic in Harley Street, insists AlloDerm is safe, effective and, crucially, obtained with the full consent of those who donate their bodies to science, or their loved ones. ‘There is no reason to have any complaints about it,’ he said.

But is this really the case? Do those who bequeath their bodies to medical science expect to end up satisfying the vanity of women in London and elsewhere?

Consent forms are literally thrust into the hands of the bereaved in casualty departments or hospital corridors by scavengers – sorry, representatives – working for U.S. tissue banks. The families are not paid for their largesse.

The crucial information that the remains of the body may also be used in ‘reconstructive or cosmetic surgery’ is buried in the small print (until recently the word ‘cosmetic’ wasn’t even included in the form).

‘When people have died, relatives are not listening properly,’ says Dr Arthur Caplan, professor of medical ethics at the University of Pennsylvania.

‘They have no idea that tissue might be processed for the cosmetics industry.

I have consistently argued that there should be more regulation in this area.’ Almost as soon as a signature is obtained, a loved one’s remains are whisked off in a freezer chest to a tissue bank facility. Relatives assume they will be used to help the desperusesately ill or perhaps further the cause of medical research. Instead, they often enter the cosmetic supply chain. So how does it happen?

Unlike Britain, where tissue banks are affiliated to hospitals and universities, those in America are independent enterprises.

Of course, tissue banks deal directly with hospitals. But there is also big money to be made from the cosmetics market. Or to put it another way: one square foot of skin equals $1,000.

It is illegal to make a profit from the sale of human tissue in America. But tissue banks can get round this by charging large ‘handling and processing’ fees, which is within the law.

In other words, it costs $1,000 to ‘handle and process’ one sq ft of skin, $2,000 for two sq ft, and so on. It is marked down as a fee – not profit.

Buyers include pharmaceutical giant The LifeCell Corporation based in New Jersey. LifeCell is also the firm that produces AlloDerm. The same principle applies when the firm sells the products to doctors working at clinics like 112 Harley Street.

A spokesman for LifeCell said the firm did not market products for the cosmetics industry, and it was up to surgeons to decide how they use products like AlloDerm. ‘Doctors can take it and use it for almost anything they want.’ Does Dr Kirwan – who also works at the private Highgate Hospital in North London and at the Hospital of St John

and St Elizabeth in St John’s Wood – inform clients about the ‘ ingredients’ of AlloDerm? He declined to say when we contacted him again.

The truth is, however, that most women who want full lips probably don’t care.

Rene Chapman, 33, is a businesswomen who splits her time between Knightsbridge and New York. ‘I knew one of the components of Allo- Derm was human tissue,’ she said.

‘It sounded a bit creepy at first but it is produced by a reputable firm and I wanted nice lips.

‘The operation for AlloDerm implants is straightforward.

Afterwards, you experience a burning sensation in your lips and you can’t go out for several days because of the swelling. But it’s worth it.

‘My lips look very natural, and whenever I tell people what I have had done, they can’t believe it.’ How different from the generation of women who depended on the ‘Avon Lady’ and the cosmetics counter at their local department store for all their beauty needs.

‘Cadaver collagen’ is only one of the ‘extreme beauty’ treatments on the cosmetics shopping list of a growing number of British women who have Botox during their lunchbreaks and can buy other ‘miracle’ products over the internet.

Among them is a cream called TNS Recovery Complex. Anyone who watched TV’s Celebrity Love Island recently might have heard model Nikki Ziering extolling the virtues of this anti-wrinkle cream to fellow islanders Jayne Middlemiss and Rebecca Loos, claiming: ‘It’s the most amazing stuff.’ Perhaps. But it is probably fair to assume that Miss Ziering is unaware of the provenance of TNS, which contains Nouricel-MD – that’s the scientific word for an active ingredient derived from the foreskin of a circumcised baby.

Not so long ago, could anyone – apart from the most warped horror writer – have imagined that such a product would end up on the faces of British women?

In fact, the gel comes from a single foreskin that was donated to – yes, you’ve guessed it – an American pharmaceutical company, called Skin Medica, more than 15 years ago.

The tissue cells of that foreskin were then replicated in a laboratory.

Why a foreskin? Because it contains proteins, collagen, elastin and hyaluronic acid – all the things that ageing skin tends to be deficient in.

Skin Medica claims its products are not sold over the counter as they form ‘part of a medically supervised skincare regime managed by physicians’.

However, a number of internetbased firms are more than happy to sell direct to customers.

One is Revitalise UK, run by Chris Pattison. The cream costs Pounds 195 and he has sold more than 100 ‘units’ of TNS in the past two months – an income of Pounds 20,000.

‘If someone asks me what’s in the product, I will tell them, but no one has been put off when I’ve told them about it. But most people simply don’t ask,’ says Pattison.

‘Ultimately, unless they have very sensitive skin, people just aren’t concerned by what’s in a product, they just want to know it works.’ He’s right, of course. Wendy Lewis, herself a beauty consultant, is proof, if further proof were needed. ‘I’ve been using it for a couple of years and apply it twice a day to my face.

I was impressed, rather than put off, by the science behind it and, like a lot of women, I was prepared to try it if it worked, and TNS certainly works for me,’ she said.

So, that’s lips and faces. What about hair? One woman who lives in a Docklands apartment overlooking the Thames is something of an expert in this field.

Svetlana Bobrakova runs a company called Euro Hair London.

For just one kilogram of 18in hair – sufficient for five people’s extensions – she charges about Pounds 950 for a brunette and Pounds 1,070 for blonde.

But it’s not the price that is the issue here. It’s where her ‘products’ come from – the heads of impoverished Russian children whose naturally healthy hair is highly prized.

In the Siberian city of Novosibirsk, for example, there is a sign outside the bus stop in Karl Marx Square which announces ‘wonderful prices’ for good-quality hair. The people who supply ‘that wonderful hair’ are children reduced to selling their hair for about 70 roubles a time (about Pounds 1.40) simply to eat.

‘Virgin Russian hair’ – considered the thickest and most luxuriant on the market – is becoming a ‘must have’ accessory in fashionable London where you can expect to pay Pounds 600-plus for it.

Demand has never been greater (Victoria Beckham has worn this so- called Virgin Russian hair) and has doubled over the past three years. Miss Bobrakova, a beautiful young Muscovite in her 30s, is helping to meet that demand. Her company, which imports hair from Eastern Europe, sells to many top British stylists.

It is certainly profitable, but is it ethical? As we know, ‘ethics’ and the ‘beauty industry’ are not always compatible. The picture which emerged this week shows that across the globe, from China to Russia to America, scientists are pushing the boundaries of what is acceptable in the beauty industry.

And if the source of these dubious treatments may be thousands of miles away, it’s clear that scores of British women are either creating a demand for them to be imported to London, or are travelling overseas themselves.

Indeed, wealthy British women are even now embarking on ‘ cosmetic breaks’ to Miss Bobrakova’s native Moscow. No, not for hair extensions, but for something far more sinister on offer at the city’s Cellulite Clinic, an upmarket beauty treatment centre.

It is here that women are promised eternal youth – an antiageing injection that the doctor at the clinic boasts is composed of cells taken from the nutrient-rich umbilical cords and placentae of aborted foetuses.

Many of the foetuses have been deliberately left to grow in their mothers’ wombs until five months old – the point at which they are considered to be optimally potent in terms of their ability to promote regeneration and repair.

The women are not being paid to have abortions. They have already decided on this course of action.

But, scandalously, they are encouraged to wait until ‘five months’ in return for payment. The abortions themselves are performed at other centres.

Surgeons at the Cellulite Clinic, and many others throughout the city, are simply exploiting a loophole in Russian law which permits the extraction and storage of embryo stem cells but doesn’t explicitly specify the use they can be put to.

As a result, clinics are free to use foetal cells for cosmetic injections without fear of prosecution.

According to someone who has worked at the clinic, the treatment, which costs between Pounds 2,500 and Pounds 20,000, is ‘particularly popular with British and American women’.

If the thought of having stem cells from a placenta injected into you is too much to bear, perhaps you’d consider something less invasive from the ‘placenta product’ range, such as a placenta shampoo or a placenta face mask.

According to some sources it is commonplace for many hospitals to sell placentas to cosmetic companies.

One firm in America, Plazan Skincare, told the Mail that the cells used in their products are collected from maternity wards ‘only after the mother has given birth to a healthy baby and a donation consent form has been signed’.

Plazan claims it is offering ‘a service of timeless beauty’ on its glossy website, and admits it was one of the few manufacturers in the world offering ‘skincare products enriched with foetal cell components’.

It may be better regulated than the Russian clinics, but the basic facts remain the same.

So, ‘cadaver implants’ in Harley Street – and the potential exploitation of the dead and the bereaved who facilitate them – foreskin cream and now aborted foetuses.

Just how far will women’s vanity push the limits of human decency?

Additional reporting:

BOSTON, Sept. 16 /PRNewswire/ — A Newton woman was sentenced today in federal court for making false statements in connection with a Food and Drug Administration approved clinical study.

United States Attorney Michael J. Sullivan and Kim A. Rice, Special Agent in Charge of the Food and Drug Administration’s Office of Criminal Investigations, Metro Washington Field Office, announced today that ANNE BUTKOVITZ, age 48, of Newton, Massachusetts, was sentenced by U.S. District Judge Douglas P. Woodlock to 1 year of probation and a $1,000 fine. BUTKOVITZ pleaded guilty on June 7, 2005, to an Information charging her with one count of making false statements. As part of her plea agreement with the Government, BUTKOVITZ also agreed that she would never participate in any manner in the conduct of studies intended for or required for submission to the FDA.

At the earlier plea hearing, the prosecutor told the Court that, had the case proceeded to trial, the evidence would have proven that in May, 2001, BUTKOVITZ became the clinical study coordinator at a pediatric practice for a pharmaceutical company’s clinical trial entitled “Safety and Efficacy of Pentavalent (G1, G2, G3 G4 and P1) or Human-Bovine Reassortant Rotavirus Vaccine in Healthy Infants.” The objective of the study was to evaluate the efficacy and safety of the pharmaceutical company’s rotavirus vaccine against rotavirus disease in children. Rotavirus causes severe diarrhea in infants. A similar rotavirus vaccine marketed by another pharmaceutical company had previously been discontinued due to concerns that it caused intussusception, also known as blocked bowel syndrome.

According to the clinical study protocol to evaluate safety, all study subjects were followed after each vaccine dose for all serious adverse experiences (“SAEs”), including intussusception. To determine if SAEs occurred, the study protocol required the study site to contact the subject’s parent(s) at three intervals after each of the three vaccinations. At the time of each contact, the study site was required to indicate on a Case Report Form whether contact was made, the date of contact and responses to a series of questions.

In her role as the clinical study coordinator, BUTKOVITZ was responsible for, among other things, making all follow-up contacts with the study subjects as required by the clinical study protocol. It is alleged that BUTKOVITZ did not make the required contacts with parents/guardians of the clinical study yet falsely stated on the Case Report Forms that she had made the contacts.

BUTKOVITZ was specifically charged with making false statements on September 25, 2002, in connection with the clinical study by falsely representing that she had received certain information regarding the “serious adverse experiences” of a patient in the clinical study.

After learning that BUTKOVITZ had not made the safety contacts required by the protocols of the clinical study, on February 5, 2003, the pharmaceutical company removed the pediatric practice and the data it had generated from the study.

The case was investigated by the Food and Drug Administration’s Office of Criminal Investigations. It was prosecuted by Assistant U.S. Attorney Jeremy Sternberg in Sullivan’s Health Care Fraud Unit.

U.S. Attorney

CONTACT: Samantha Martin of the U.S. Attorney’s Office, +1-617-748-3139

People with frontotemporal dementia have shorter life spans than Alzheimer’s patients, study finds

A family confronted with Alzheimer’s disease may well believe that it is the worst thing that can happen, but neurologists are describing a related brain condition that is even more troubling.

It’s called frontotemporal dementia, named after the parts of the brain that it attacks — the upper lobes of the front part of the organ. Alzheimer’s, by comparison, affects the entire brain.

And while people with Alzheimer’s disease suffer progressive loss of memory and ability to function, those with frontotemporal dementia may act wildly and bizarrely, veering into theft, sexual deviancy and other uncontrolled acts, according to experts.

“We know that many of these patients are said to be crazy and wind up in jail rather than in a hospital,” said Dr. John Q. Trojanowski, director of the University of Pennsylvania Institute on Aging.

And the condition is a killer, according to a study in the current issue of the journal Neurology to which Trojanowski contributed. The study found that people who had frontotemporal dementia died much faster than those with Alzheimer’s disease.

The 395 Alzheimer’s disease patients died 8.7 years after diagnosis. The average survival time for the 177 people with frontotemporal dementia was three years. Some Alzheimer’s patients lived as long as 11.8 years after diagnosis, while the longest survival time for those with the other condition was 5.7 years, the study found.

There are several possible explanations for the difference, said Dr. Erik D. Roberson, a research scientist at the University of California, San Francisco’s Gladstone Institute of Neurological Disease, who took part in the transcontinental study and was lead author of the journal report.

One reason is that people with frontotemporal dementia are likely to get Lou Gehrig’s disease, a fatal neurological disorder in its own right, Roberson said. Another is that “the patients’ withdrawal and social barriers might lead them to be institutionalized early in the course of the disease, and there might be changes in quality of medical care they get,” he said.

The most tantalizing possibility is that the tangles of tau protein found in the brains of patients with Alzheimer’s disease might have a protective function, Roberson said. Frontotemporal dementia patients who survived longest were those who had tau-positive inclusions in their brains; those with no such inclusions died fastest, he said.

“Are these inclusions part of a problem or a brain’s attempt to solve a problem?” Roberson said. “Some data in Huntington’s disease indicate that tau-positive inclusions are a good thing that protect the brain.”

Trojanowski has an even simpler explanation: It is simply the nature of frontotemporal dementia to be fast-moving, just as some forms of cancer are more malignant and kill more quickly, he said.

There is no immediate medical application for the finding, Roberson said. But if there are trials of a treatment in the future, patients would have to be tested more frequently than is done in trials of Alzheimer’s disease, he said.

The possibility of such treatments and such trials exists, Trojanowski said, “because if we know what is broken, we can try to fix it.”

But the most important message is for families of those people diagnosed with frontotemporal dementia, he said. In simplest terms, “they have to plan for what is now an inevitable death.”

It is one of those facts that has to be accepted, Trojanowski said. “I would want to know if my dad or mother or wife is to die in five years,” he said. “There are different arrangements than if they will live for 10 years.”

There is a possible application of the finding about tau inclusions, said Dr. David M. Blass, director of the Frontotemporal Dementia Clinic at Johns Hopkins Medical Institutions. Studies to detect those inclusions could give information about the rate at which the condition would progress, he said.

“The importance of this study is that it looks at a very large group of patients that goes beyond any individual’s clinical experience,” Blass said. “For families with this condition, knowledge of prognosis is exceptionally important. Any improvement in the knowledge we can give families is of value in planning and making peace with the conditions of their loved ones.”

More information

Frontotemporal dementia is fully explained by Johns Hopkins University

NEW YORK — Many women worldwide continue to undergo a painful procedure during childbirth that experts say should be used only in limited circumstances, a new study shows.

The procedure, called episiotomy, involves making an incision to enlarge the vaginal opening during childbirth. Episiotomies were once performed routinely in the U.S. and elsewhere, in part because doctors believed it helped prevent vaginal tearing that can occur during delivery.

But in many countries, rates of episiotomy have fallen sharply since the 1980s, after mounting evidence began to show no benefit from routinely performing the procedure. The incision takes weeks to heal, during which time walking, using the bathroom and even sitting can be painful. At worst, episiotomy can lead to a laceration in the anal sphincter, a difficult-to-repair tear that can cause long-term incontinence.

Though episiotomy is necessary in some cases to ensure a safe delivery, a range of professional medical organizations now agree that it should be used sparingly — in cases of fetal or maternal distress, for instance.

There is, however, no agreement on what constitutes an acceptable rate of episiotomy. And in the new study, Canadian researchers found that rates vary widely from country to country, among regions within the same country, and even among providers in the same medical network.

Episiotomy rates are generally highest in Asia and Central and South America, while they are lowest in English-speaking countries and some European nations, the researchers report in the medical journal Birth.

Sweden had the lowest rate, at less than 10 percent of vaginal births in 1999-2000. In contrast, it’s estimated that in Guatemala and Taiwan, all first-time mothers who delivered vaginally received an episiotomy.

In Western Europe, episiotomy rates for all vaginal deliveries ranged from 13 percent in England, in 2002-2003, to 87 percent in Spain, in 1995.

In the U.S., episiotomies were performed in one third of vaginal deliveries in 2000, the researchers found. But, as in Canada and other countries, the rate varied according to region; it was highest in the Northeast, at 38 percent, and lowest in the West, at 27 percent.

Exactly why episiotomy rates vary so widely among nations is unclear, the study’s lead author, Dr. Ian D. Graham of the University of Ottawa, told Reuters Health.

Cultural ideas about women and about childbirth, such as the notion that it should be treated as a medical condition, could be at work, according to the researcher. In developing countries, he added, high episiotomy rates could also be the result of doctors “importing” a Western-style medical intervention because they see it as “more progressive” than traditional, low-tech births.

The fact that episiotomy rates vary substantially within countries — and, according to a number of international studies, within single institutions — is surprising, according to Graham.

“It does mean that the reasons for doing the episiotomies must be related to differences in the providers’ attitudes and practices,” he said.

In English-speaking countries, Graham noted, doctors should by now be well aware of guidelines calling for restricted use of episiotomy.

So, he said, women should ask their providers about their personal attitudes toward the procedure to ensure that those beliefs match their own.

SOURCE: Birth, September 2005.

Washington, DC–September 13, 2005–In the wake of Katrina, the public health threats from infectious diseases in hurricane-devastated areas are more likely to come from milder, more common infections rather than exotic diseases. These common infections can often be prevented using simple hygiene measures and a little common sense.

“Deadly diseases, such as typhoid or cholera, are unlikely to break out after hurricanes and floods in areas where these diseases do not already naturally occur,” says Ruth Berkelman, MD, Chair of the Public and Scientific Affairs Board of the American Society for Microbiology. “The greatest threats to the people in the affected areas are going to be from diseases that were already there.”

Dr. Berkelman is the Rollins Professor and Director of the Center for Public Health Preparedness and Research at the Rollins School of Public Health at Emory University. She is a former Assistant Surgeon General of the United States and former deputy director of the CDC’s National Center for Infectious Diseases (NCID).

Common infectious disease problems in New Orleans in the coming weeks are likely to be skin and soft-tissue infections, most likely from cuts, abrasions and wounds. The primary culprits will be Staphylococcus and Streptococcus bacteria, both of which can generally be treated with available antibiotics. Diseases caused by consumption of contaminated food or water as well as diseases caused by mosquitoes or other insect bites are also a threat.

Vibrio vunificus can also cause serious infections, either wound infections or blood poisoning (septicemia); V. vulnificus is a bacterium that is normally present in Gulf Coast waters and is usually contracted by eating tainted seafood. It is primarily a threat to people with weakened immune systems or liver dysfunction. The CDC has confirmed 15 infections with V. vulnificus, 3 of which were fatal. These cases have occurred in areas other than New Orleans where the water has greater salinity.

Another concern is diarrhea and gastrointestinal illnesses from the flood waters. Short bouts of diarrhea and upset stomachs sometimes occur after natural disasters and can be caused sewage contamination of the water. Although at high levels in floodwaters, the E. coli found in New Orleans is the type commonly associated with fecal contamination and is not the E. coli H7:O157 strain that can cause serious kidney disease and bloody diarrhea.

“At this point in time, I think it is just common sense to continue drinking only bottled water unless authorities have tested the water now being piped into some facilities and have declared it safe to drink,” says Berkelman. “To also prevent risk of infection, people should practice basic hygiene, frequently washing their hands with soap and clean water or disinfecting hands with an alcohol-based hand cleaner. Individuals should not eat food that has been exposed to flood waters or that has not been properly refrigerated.”

One common misperception is that the body of a person who died as the result of the hurricane and is still in the city poses a risk of infection.

“Decaying bodies pose very little risk for major disease outbreaks,” says Berkelman. Furthermore, mosquitoes do not spread disease by feeding on dead bodies. There is, however, a risk of mosquito-borne diseases such as West Nile because mosquitoes breed in standing water. Appropriate pest management, including addressing the need to get rid of standing water, is an important public health measure, she said. A bacterial disease, leptospirosis, may be caused by exposure to water contaminated by rodent urine and can be treated successfully with antibiotics.

Over the long term, mold may also pose a threat. Mold growth is an indicator of excess moisture, and much will need to be done to dry out New Orleans and clean up mold growth. Some environmental molds can cause allergic reactions.

On the World Wide Web:

American Society for Microbiology

NEW ORLEANS (Reuters) – The two long, red scratches are a
dead giveaway.

“You got snake bit,” Dr. John Twomey tells the middle-aged
woman who has walked into his disaster center for care.

Twomey, a burn surgeon, is chief medical officer of a
tented hospital set up by a federal Disaster Medical Assistance
Team on the grounds of the West Jefferson Medical Center, just
outside New Orleans proper.

The woman, who cannot be identified for medical privacy
reasons, is one of the 1,500 to 2,000 patients who have been
coming through the temporary facility set up last week.

Even though such cases could occur any day, accidents
always increase exponentially after hurricanes and other
disasters as people seek to clean up the damage.

Teams of nurses, doctors, paramedics and pharmacists from
around the United States are working under the Federal
Emergency Management Agency to supply emergency medical care
for the people who remain in the New Orleans area.

Twomey says they have seen the full gamut of medical
emergencies, from stomach illness to people who stepped on
nails, to the homeowner bitten by a snake as she tried to clean
up from Hurricane Katrina.

“I was wearing gloves to clean out my refrigerator,” the
woman says, somewhat embarrassed. “At least I got that right.”

But she was wearing flimsy shoes in the summer heat.

She had returned to her home in nearby Plaquemine’s Parish
after having fled Katrina. Her house was in fairly good
condition, but the refrigerator was full of rotten, smelly food
after days with no electricity.

She dragged it out into the back yard to clean it.

“Of course the grass is tall right now,” she said, and
added: “It’s usually manicured.”

She stepped back from her task. “I felt something sting me
and I felt it burn,” she said. Certain it was a bee, she went
to a nearby Red Cross emergency assistance center, set up to
aid people from nearby whose homes were flooded.

FAIRLY COMMON SNAKES

They sent her to West Jefferson Medical Center, where she
was intercepted by the DMAT team and an eager Twomey.

“I read the manual on snake bites this morning,” said
Twomey, a burn surgeon from Hennepin County Medical Center in
Minneapolis.

“This looks like a glancing blow,” he tells the woman. “We
won’t use any antivenin now but come back if it starts to
swell. He applies an antibiotic “because snakes have relatively
dirty mouths,” and sends a relieved patient on her way.

It could have been a water moccasin, a copperhead or a
rattlesnake, all fairly common in these parts.

So far, such cases seem to be more frequent than the feared
outbreaks of infectious disease.

Although the floodwaters are a stew of sewage and
chemicals, many people have been able to avoid infection so
far.

Water and sewer service has been restored to some parts of
New Orleans and neighboring Jefferson Parish but the U.S.
Centers for Disease Control and Prevention warns that while the
water looks clean, it is not safe to drink or to bathe in.

“We have seen people who have done only one brushing of
their teeth with water out of the tap and within six to eight
hours they are violently ill,” said Twomey.

He said they are treating these patients with antibiotics
and Gatorade.

“The national news has people afraid they can’t even go
outside without a mask and a full body suit,” said Curtis
Allen, a spokesman for the CDC in Atlanta who is in New
Orleans.

“There is very little disease here,” Allen said. “We have
not been seeing the diseases that many people around the
country feared.”

BRITISH scientists have been given the go-ahead to create a human embryo with two genetic mothers.

The Human Fertilisation and Embryology Authority reversed an earlier ban on the research project at Newcastle University.

The programme will involved transferring some genetic material from the fertilised egg of one woman into an egg from another.

The aim is to avoid mothers passing a range of incurable genetic diseases to their unborn babies.

Critics branded it a ‘biotechnological nightmare’ and another step towards a chilling world of reproductive cloning, currently banned in the UK.

Matthew O’Gorman, of the charity LIFE, said: ‘This decision is utterly unethical, abhorrent and contrary to public opinion.

The HFEA is relentlessly imposing its libertarian agenda on the people of this country against their wishes. The Government must act to disband it immediately.’ The decision was welcomed, however, by fertility specialists, who said it could relieve the suffering of families afflicted with a genetic curse. Supporters of the work, who

include the Muscular Dystrophy Campaign, say one in 5,000 children and adults are at risk of developing one of the incurable conditions involved.

The research proposes eradicating the legacy of faulty genes carried in the mother’s mitochondria the energy ‘ batteries’ that power most cells in the body.

The mitochondria have their own DNA, inherited only from the mother. Faults in this can result in some 50 disorders affecting the brain, muscles, heart and liver.

The research will involve transferring most of the genetic material out of a fertilised egg containing ‘bad’ mitochondria.

It will then be put into another woman’s unfertilised egg containing ‘good’ mitochondria. None of the resulting embryos will be implanted.

If the work should eventually lead to approval for a child to be born, it would share the overwhelming majority of its DNA with its parents meaning it would not have the physical characteristics of the second mother. But there are fears that such genetic changes could produce unforeseen defects in future generations.

A leading psychologist said last night it would be a mistake to ever tell a child he has three parents.

Dr David Holmes of Manchester Metropolitan University said: ‘It could make them insecure and doubt the people who have brought them up.’ The new research will be headed by neurology professor Doug Turnbull and Dr Mary Herbert, scientific director of Newcastle Fertility Centre.

A spokesman for the team said the granting of a licence was ‘the very first step in a very difficult process. While the technique has been found to be safe in animal embryos, it will be very important to determine whether it can be safely used in human eggs’.

The programme will use fertilised eggs from couples undergoing IVF treatment which have been rejected as substandard.

The Newcastle licence application was originally rejected by the HFEA because it was thought to be outside the 1990 Act governing fertility research.

An appeals committee reversed the decision after hearing evidence from some of the world’s leading geneticists. It called the work ‘necessary and desirable’.

Fertility specialist Professor Peter Braude of King’s College, London, said ‘I am delighted to hear that this important work will be pursued in the UK, and that the HFEA have had the wisdom to ‘If it works and is safe it will be the answer to the prayers of those inflicted with these awful disorders.’

Alastair Kent, chairman of the Genetic Interest Group, said: ‘Only a very small number of genes are involved and this is a humane and sensible to way to carry out research that may lead to the treatment and eradication of these lethal diseases.’ But LIFE’s Mr O’Gorman said any step towards creating humans with three genetic parents should be resisted.

He said: ‘We support all ethical license it.

attempts to find cures for disabilities but one cannot countenance the deliberate creation of genetically abnormal children, however noble the motive may be.

‘This is a biotechnological nightmare. Decisions of this magnitude should be made by Parliament, not an unelected and unaccountable quango.’ It was announced in May that scientists at Newcastle University had cloned a human embryo for the first time in Britain.

They hope the work will lead to treatments for degenerative diseases such as Parkinson’s and Alzheimer’s, or for the paralysed victims of spinal injuries.

But critics say every advance in therapeutic cloning could help mavericks who want to create cloned babies. Reproductive cloning is illegal in the UK.

The tragic twins AN earlier experiment to create babies with two ‘genetic mothers’ ended in tragedy in China.

U.S. experts, working there because the process was banned everywhere else, used the shell of a donated egg to rejuvenate a fertilised one from a woman whose infertility problem was caused by poor-quality eggs.

The mother became pregnant with twins but lost both before birth, despite carrying the second for six months. Tests showed they had no genetic defects but the team halted their work and China banned any more such projects.

The experiment, which came to light two years ago, is not the same as those planned in Britain.

In 2001, scientists in New Jersey reported that 15 healthy children had been born in a programme with used donated mitochondria from fertile women to treat infertile ones.

WHAT THE SCIENTISTS WANT TO DO

Bad Mitochondria PRONUCLEI Good Mitochondria They plan to experiment on a fertilised egg from a woman who carries faulty mitochondrial DNA.

The scientists will remove tiny structures called pronuclei, which will then be put into a fertilised egg from another women with only healthy mitochondrial DNA.

Although this second egg has been fertilised, the pronuclei DNA from the male and female that made this egg will be removed.

The result would be an embryo with pronuclei DNA from the parental egg and sperm but mitochondria from the donor egg.

This embryo would share almost all its physical characteristics and DNA with its parents.

But scientists believe it would also be free of the risk of mitochondrial disease.

Cambodia’s drug abuse increases

PHNOM PENH, Sept. 8 (Xinhua) — Cambodia’s drug abuse and trafficking is growing, announced the National Authority for Combating Drugs (NACD) on Wednesday, newspapers reported on Thursday.

Drug circulation in Cambodia has increased without fail and drug abuse is becoming a serious problem in 15 provinces and towns across the country, Interior Minister Sar Kheng was quoted by Cambodia Sin Chew Daily as saying.

In addition, the creation of drug rehabilitation facilities is proceeding slowly, causing people to lose confidence in the government’s fight against the growing narcotics problem.

The number of drug users has reached nearly 7,000, most of them in the capital of Phnom Penh. “But the real number of users is probably much higher,” said Teng Savong, secretary general of the NACD.

Meanwhile, Sar Kheng praised the government enhanced the crackdowns on drug rings since the beginning of this year.

During the first eight months of the year, 265 networks were dismantled, compared to 248 in 2004, and 230,000 amphetamine pills were seized and 514 people arrested.

Sar Kheng urged the government and authorities concerned to continue their crackdown on the drug trafficking, and to further strengthen the propaganda campaign to let more people know the dangerous of the drug.

Maureen “Moe” Guilfoyle can’t jump like she used to.

But she can still jive. She can still sweat.

And she can still wear that Madonna-style headset.

The dance-loving Omaha secretary, who at age 53 became one of the oldest new Jazzercise instructors in America, had to give up her beloved dance workout last fall after a slip while gardening injured her hip.

After she healed, dancing and jumping with her usual vigor were impossible. And the 30 pounds she had gained while sidelined didn’t help.

She didn’t give up, though. With her doctor’s OK, she returned to Jazzercise classes as a student in January, doing lowimpact versions of the moves while younger and fitter types bounced and bounded across the floor.

And next week, the 58-year-old will don her headset microphone once again and take the stage to lead a different sort of Jazzercise class.

Called Jazzercise Lite, it’s a low-intensity version of the dance- inspired workout. It’s intended primarily for the 50-plus, baby boomer set. But Guilfoyle said it also will serve anyone who is uncomfortable doing high-impact aerobics because of age, weight or health conditions. While Jazzercise outlets across the country have offered Lite versions for years, Guilfoyle’s appears to be the first Lite-only class in the Omaha area.

She wished she’d had one while she was recovering.

“They always show the low-impact modification in a regular Jazzercise routine, but it’s not the same,” she said. “There’s a lot of pressure in the mixed classes. You don’t want to be the only one doing low impact.”

Guilfoyle said the Lite class still includes heart-thumping music, dance moves and strength training. But it omits the bouncing, hopping and jumping, and slows the pace of turns to limit injury to knees, hips and other joints. It also adds back support on sit-ups and other floor exercises.

“We’ll still be increasing our heart rate, blood flow and circulation and doing all those good things for your heart and lungs, muscles and bones,” she said. “We just won’t hop when we do it, and we’ll be safe.”

Guilfoyle said she started the class for herself and other baby boomers who want to keep exercising as they age.

“You can’t just sit down and stop moving. Because, eventually, you won’t ever be able to get up,” she said. “I can imagine doing low impact until I’m 70 or 80.”

Starting next week, Jazzercise Lite will be offered at 3:30 p.m. Mondays and Wednesdays and 10:30 a.m. Saturdays at the Omaha Jazzercise Center, 8558 Park Drive. Cost is $8 for a day pass, $88 for eight weeks or $37 a month if you set up an automatic bank withdrawal for payment. For information, call 331-2120.

Can’t jump?

Tips for exercisers limited by age or injury: Don’t quit, but do modify and get a doctor’s OK. Choose low impact or beginner versions of exercises you enjoy. Don’t skimp on warm-ups. They help prevent further aches and injury. Slow the pace, particularly for motions that involve twisting of the joints. Lose the bounce. Instead of heel hops and skips, do heel touches and march in place. Source: Maureen Guilfoyle, Omaha Jazzercise Lite instructor.

The statistics are staggering.

More women in the United States have been victims of domestic violence than have been raped, mugged or injured in auto accidents combined. Nearly 4 million women suffer from domestic violence every year and 30 percent of female homicide victims are killed by their husbands or boyfriends. These are just a few of the facts compiled by Rainbow Services, a San Pedro-based group dedicated to ending the cycle of family violence.

Abusers play a Mad Hatter’s cycle of aggression followed by periods of apologies and kindness. Victims flip-flop between emotions of love and hate under a constant layer of fear. They stay in a bad situation for fear of losing their children or feeling emotionally or financially dependent. Often they believe they have nowhere to go or are terrified at the reaction of their abuser, the center’s counselors say.

In truth, they are far from alone and public outrage is growing. Today a woman is beaten in the United States every nine seconds, according to FBI records, and family violence costs the nation from $5 billion to $10 billion annually in medical expenses, police and court costs, shelters, foster care, sick leave and lack of productivity. Despite this, there still are three times as many animal shelters in the United States as there are shelters for battered women.

Organizations such as Rainbow Services are constantly bucking the tide of public ignorance or apathy with their fervent mission to end the cycle of family violence. The organization’s first task is to help each victim survive and remain safe.

At Rainbow Services, the process usually begins with a phone call to its 24-hour English/Spanish hotline. It receives an average of 400 calls each month. Trained staff members assess each situation and provide support, information and often immediate action at little or no cost to the caller.

Women and children in immediate danger needing to escape abuse can be met by a shelter staff member and taken to a secure and confidential emergency shelter for as many as 30 days where they receive meals, clothing, health exams, counseling, case management, legal advocacy and court accompaniment. Clients generally are sent to confidential shelters in a different community in Southern California to keep them hidden from their abusers.

After that clients working toward emotional and financial independence can stay at a transitional shelter for as many as nine months. While victims stay in shelters, trained staff can help with police reports, restraining orders and other legal procedures at little or no cost.

Despite efforts to get the word out that help is available, counselors say there still is enormous secrecy and shame surrounding a battered victim. Also the facts become blurred by persistent societal excuses protecting perpetrators such as “Oh, he just had a temporary loss of temper,” or “She goaded him into it. It’s her fault.”

Fighting fiction

Some cultural and historical traditions either condone or once allowed wife-beating. Early American settlers, who based their laws on old English common-law, allowed wife-beating as long as the switch was “no bigger than his thumb. Hence the “rule of thumb.”

The Los Angeles County Domestic Violence Council counters some of the most blatant myths. About the temporary loss of temper excuse, it maintains “the batterer makes a conscious decision to batter. It is an ongoing technique used by the batterer to enforce control through the use of fear.”

Another myth is that domestic violence only happens in poor families. The council points out there is no evidence that suggests that any income level, occupation, social class or culture is immune. “Wealthy, educated professionals are just as prone to violence as anyone,” it notes in materials given by Rainbow Services to victims of domestic violence.

The myth that violence is just an occasional slap or punch also is debunked. According to L. A. County Domestic Violence Council, more than 30 percent of women seeking care in hospital emergency rooms are there because of injuries by their domestic partners. Battered women are more likely to suffer miscarriages or have premature births.

Another myth is that if a batterer is truly sorry and promises to reform the abuse will stop. In truth, remorse and begging forgiveness are part of the method used to control victims. The sad truth is that batterers rarely stop.

A much believed myth is that infrequent episodes mean the situation isn’t serious. “The threat of abuse is a terrorizing means of control. No matter how infrequent the abuse, each event creates fear that one will happen in the future,” maintains the council.

How to help

Rainbow Services has an enthusiastic circle of supporters who range from volunteers who have taken the 40-hour training program similar to the next series from 6 to 9 p.m. Mondays and Wednesdays beginning Monday through Oct. 17. The 40 hours of training is free for Rainbow Services volunteers. For more information, call 310-548- 5450, Ext. 108.

Among the topics covered at the training course will be law enforcement response to domestic violence, cultural competency and domestic violence, batterer’s intervention groups, Tuberculosis tests, fingerprints, a tour of the outreach office, an overview of Rainbow Services, case managers and crisis intervention health and referral service, working with children and teens, sexual assault and public assistance or financial aid.

In addition to those who work directly with victims, Rainbow Services is looking for volunteers who can provide legal, administrative, fund-raising, medical, dental or computer services. The 40-hour training program is not required for these volunteers.

Since many families have to get away quickly, many arrive only with the clothes on their backs. Therefore financial contributions are welcome, as well as donations of new necessary items (such as food, clothing and hygiene products).

By Will Boggs, MD

NEW YORK (Reuters Health) – For men with urinary
incontinence that often follows prostate surgery, injections of
collagen into the area of the urinary sphincter can improve
short-term bladder control, according to a new study.

The procedure is performed via the urinary outlet, the
urethra, under local anesthesia. “Collagen is suitable in
patients who do not wish a more invasive option,” Dr. O.
Lenaine Westney from the University of Texas Houston Health
Science Center told Reuters Health.

“It is unsuitable for patients who have undergone
treatments which result in tissue damage to the urethra
(radiation or cryotherapy),” the investigator cautioned

Westney and colleagues evaluated the effectiveness of
collagen injection therapy for urinary incontinence after
prostate removal for cancer or benign prostate enlargement in
322 men.

The treatment reduced the average number of pads required
to keep dry from 5 to 3 daily, the team reports in The Journal
of Urology, and the procedure remained effective for about 6 or
7 months.

“Transurethral collagen injections are a good option for
short-term therapy in men with post-prostatectomy
incontinence,” the researchers conclude.

“Based on our population, if there is no improvement after
two to three injections, it is reasonable to assume that
injectable therapy will not be a successful treatment option
for the patient,” Westney commented.

More reliable treatments, which involve surgery, include an
artificial urinary sphincter and placement of a “sling” to
increase urine outflow resistance.

SOURCE: Journal of Urology, September 2005.

NEW YORK (Reuters Health) – Kidney damage is a constant
danger for people with diabetes, especially when their blood
pressure is high. Now European researchers report that the
addition of a drug, spironolactone, to standard blood
pressure-lowering therapy for such patients helps reduce both
blood pressure and the amount of albumin protein in urine, a
measure of kidney impairment.

Dr. Kaspar Rossing of Steno Diabetes Center in Gentofte,
Denmark, and colleagues note in the medical journal Diabetes
Care that two types of antihypertensive drugs — ACE inhibitors
and angiotensin receptor blockers (ARBs) — have protective
effects on the kidneys in diabetics who already have kidney
damage.

These drugs work by controlling the release of a hormone
called aldosterone. While they’re effective initially,
aldosterone levels may subsequently rise once more in almost 40
percent of patients, resulting in greater urinary protein
levels and a faster decline in kidney function.

To see whether supplementary treatment with spironolactone,
which is an aldosterone inhibitor, might be helpful in these
circumstances, the researchers conducted a study with 21
patients with type 2 diabetes.

While the participants continued on their recommended
antihypertensive treatments (which included diuretics, ACE
inhibitors and ARBs), they were randomly assigned to take in
addition either an inactive placebo or spironolactone for 8
weeks. They then switched to the other pill for another 8
weeks.

During spironolactone treatment, urinary albumin levels
fell by 33 percent, and their upper and lower blood pressure
readings fell by 6 and 4 points.

One patient developed dangerously lower potassium levels
and had to be withdrawn from the study, but recovered rapidly.
Otherwise, the treatment was well tolerated.

The researchers call for further studies, but conclude that
in the short term, spironolactone may offer beneficial renal
and cardiovascular protection.

SOURCE: Diabetes Care, September 2005.

Q: Would you please explain what causes diarrhea? It comes on me suddenly. Afterwards, I take a tablespoon of milk of magnesia and one or two Imodium caplets, which helps somewhat.

I watch my diet. I can’t eat fruit, some vegetables, gravy, sauces or cold cuts. Would vitamin supplements help the situation? Can you recommend anything to help the situation?

— L., Stamford, Conn.

A: Why are you taking the milk of magnesia with your bouts of diarrhea? For most people this causes looser stools. Some people use it to treat their constipation.

The formal definition of diarrhea is having frequent, watery, loose stools. And frequent, in this case, usually means more than four times in an eight-hour period.

Since you immediately take the Imodium, it’s difficult to tell if you would have had the multiple loose stools required to meet the formal definition.

Diarrhea is one of the most common signs of intestinal upset and is usually caused by an infection, which can be either due to a virus or bacteria. But diarrhea can be caused by a wide range of diseases such as diverticulitis, celiac disease, lactose intolerance and Crohn’s disease, among others.

Diarrhea is also a side effect of many drugs, and it’s good to think about that as a possibility, especially if you developed the problem within a few days to weeks after starting a new medication.

You can almost always treat diarrhea effectively at home. Certainly the most important first step it to try to determine if there’s something you’re doing that’s causing the diarrhea and stop it. In general, it’s also helpful to cut back or eliminate, at least for awhile, such things as caffeinated drinks, alcohol, milk and fatty foods.

It’s also very important to drink extra fluids to prevent dehydration. That means drinking enough so that you continue to produce your normal amount of urine.

Rest is also important, especially if your diarrhea is accompanied by fever, indicating you may have an infection. Strenuous physical activity also causes increased motility of the intestines, a good reason to use exercise as treatment for constipation.

During bouts of diarrhea, it may be helpful to adhere to the BRAT diet (i.e., to limit your food intake to bananas, rice, apple sauce and bland toast.) Over-the-counter bulk expanders or bran may be helpful, especially for chronic diarrhea.

One of the most effective drugs for stopping acute diarrhea is loperamide (Imodium is a brand name for this drug). It can be found in a number of over-the-counter preparations. Please read and follow the label carefully, don’t use it for prolonged periods of time unless advised to do so by a physician, and be very cautious in using it for young children.

If you experience any of the following symptoms, I recommend you consult a health professional.

*Your diarrhea is black or bloody.

*You have very severe abdominal pain.

*You become dehydrated.

*Diarrhea continues for more than 48 hours.

*Diarrhea comes and goes for more than 2 weeks.

(Write to Allen Douma in care of Tribune Media Services, 2225 Kenmore Ave., Suite 114, Buffalo, NY 14207; or contact him at DRFamily(AT)aol.com. This column is not intended to take the place of consultation with a health-care provider.)

Family history of stroke

High blood pressure, (hypertension)

Excessive alcohol consumption

High cholesterol

Heart disease

Abnormalities of the clotting system in the blood

You can’t change your family history but there are things you can do now like giving up smoking, eating less salt and doing more exercise, which could lower your risk of stroke and illnesses like heart disease and cancer.

Recovering from a stroke:

The type and time of recovery is dependent on the severity of the stroke.

Q Recovery is usually fastest in the first few months after the stroke.

Q There are different approaches to rehabilitation: these can include physical, speech or occupational therapy.

Q Drugs can be used to lower blood pressure: these can include aspirin, or new drugs Persantin and Asasantin.

Q The first and most important stage in recovery is to stabilise the patient and make sure he or she is comfortable. Victims are more likely to recover if they do not feel vulnerable.

NFor more information and advice call the Stroke Association on 0845 30 33 100 or visit its website, www.stroke.org.uk

Hidden danger

One in five people in the region suffer from high blood pressure which has not been diagnosed. The condition is a major risk factor for stroke and other cardiovascular diseases.

Two patients with debilitating reflux after esophagectomy are reported. Complete relief of symptoms after creation of a Roux-en-Y limb to the gastric conduit is described.

MEDICALLY REFRACTORY duodcnogastric reflux after esophagectomy, though relatively rare, can be extremely debilitating. Surgical options are limited and historically have involved resection of the gastric conduit with colonie or jejunal reconstruction, a major undertaking with significant morbidity. The following cases describe the creation of a Roux-en-Y limb to the gastric conduit, which is a less demanding operation and can safely and effectively relieve severe duodenogastric reflux after esophagectomy.

Case 1

The patient is a 41-year-old white female with a history of severe gastroesophageal reflux disease. She had failed maximal medical therapy and underwent a Nissen fundoplication. Despite this, she continued with disabling reflux and multiple admissions for aspiration pneumonia and ultimately underwent transhiatal esophagectomy. She developed an anastomotic stricture requiring serial dilatations roughly 4 weeks later. At each dilatation, bile was noted in the stomach, and biopsies showed severe esophagitis. Her stricture was ultimately relieved after multiple dilatations, however she then developed disabling bile reflux. Despite a variety of maneuvers including diet modification, strict attention to posture including sleeping in a recliner, and promotility agents, she continued with severe bile reflux causing chest pain, nocturnal biliary emesis, worsening of her asthma requiring use of four inhalers as well as occasional steroids, and multiple admissions for aspiration pneumonia. She ultimately was referred to our institution for evaluation.

She was taken to the operating room for creation of a Roux-en-Y limb to the gastric conduit. The gastric pull-up and duodenum were identified and the pyloroduodenal junction just below the hiatus identified. The pyloroduodenal junction was encircled along its serosal layer with care taken to preserve the mesenteric blood supply and was divided using a stapler just distal to the pylorus. The jejunum was then divided approximately 15 cm distal to the ligament of Treitz and brought in a retrocolic fashion to the pylorus. An endto-end two-layer handsewn anastomosis was then constructed between the pylorus and the jejunum. Gastrointestinal continuity was then restored by creating a side-to-side functional end-to-end stapled anastomosis between the cut end of proximal jejunum and the Roux limb approximately 45 cm distal to the divided pyloroduodenal junction (Figs. 1-3).

She did well postoperatively and continues to do well now 5 years later. She swallows normally without reflux symptoms and takes no medications. Additionally, her asthma has improved markedly with only occasional use of an albuterol inhaler.

Case 2

The patient is a 56-year-old white male with a history of severe gastroesophageal reflux disease. His symptoms were refractory to medical therapy, and biopsies showed Barrett changes. He underwent a laparoscopic Nissen fundoplication, and his symptoms, although not fully relieved, were able to be medically managed. He continued to undergo surveillance endoscopy, and ultimately biopsies revealed Barrett with high-grade dysplasia. He therefore underwent transhiatal esophagectomy. Approximately 8 weeks postoperatively, he developed dysphagia, and endoscopy revealed an anastomotic stricture. There were a large amount of bile-stained secretions in the esophagus and stomach, and biopsies revealed severe esophagitis. Despite weekly dilatations over the course of several months, he would restricture rapidly, and he ultimately underwent placement of an esophageal stent across the anastomosis, which relieved his dysphagia. Unfortunately, he then developed disabling reflux resulting in chest pain, frequent biliary emesis, and aspiration. The stent was removed, however, he restrictured within 10 days prompting reinsertion of the stent and referral for consideration of colon interposition. He was offered a Roux-en-Y as an alternative.

FIG. 1. Postesophagectomy.

FIG. 2. Creation of Roux-en-Y limb.

FIG. 3. Completion of Roux-en-Y limb.

He was taken to the operating room for creation of a Roux-en-Y limb to the gastric conduit. The procedure was identical to case 1 except that the pylorojejunal anastomosis was constructed with a GIA stapler for the back wall and the anterior defect closed in two layers as described by Orringer et al. for esophagogastric anastomosis.1

He has since recovered well and is swallowing without difficulty and without reflux symptoms now 18 months later. His esophageal stent remains in place.

Comment

Esophagectomy is the standard therapy for esophageal cancer and is occasionally required in benign conditions as well. Although there will always be disagreement as to the optimal approach to esophagectomy (transhiatal vs Ivor-Lewis) and the need for pyloric drainage (pyloromyotomy or pyloroplasty vs no drainage), the majority of studies have shown essentially equivalent results regardless of approach.2, 3 One common feature of esophagectomy, regardless of technique used, is that it promotes the development of reflux. The combination of truncal vagotomy, impaired motility of the esophageal remnant and gastric conduit, elimination of the lower esophageal sphincter, and placement of the stomach in the thorax in which it is exposed to negative intrathoracic pressure predisposes to duodenogastric reflux. The presence of duodenogastric reflux after esophagectomy is 60 per cent to 80 per cent.4, 5 Although its occurrence is common, its symptoms, including regurgitation, cough, aspiration, and “cervical heartburn” are usually easily controlled with a combination of medicines and lifestyle modification. In rare instances, however, as in the two cases described above, this reflux can be lifestyle limiting and refractory to treatment. In these situations of medical failure, options are limited and often revolve around resection of the conduit with reconstruction using colon or jejunum. Due to the magnitude of this operation and its significant morbidity profile, it is often avoided and the patient unfortunately is obligated to continue with debilitating symptoms.

The creation of a Roux-en-Y gastrojejunostomy is well described and widely used for the correction of severe symptomatic duodenogastric reflux after gastricsurgery. Overall, long-term results have been favorable using this remedial operation with the majority of patients reporting relief of symptoms.6, 7 Given this success, it would stand to reason that its application to the problem of debilitating duodenogastric reflux after esophagectomy would be physiologically sound. In fact, it could be postulated that it may meet with higher success, as its main problem after gastrectomy is poor motility of the denervated stomach and development of the “Roux stasis syndrome,” and its use in the setting of previous esophagectomy with a “tubularized” stomach may actually allow better drainage and avoidance of this problem.

Both patients described above had complete relief of symptoms with this procedure. Additionally, we have recently had the opportunity to perform this procedure on another similar patient who although early in his postoperative course (approximately 2 months) appears to have complete resolution of symptoms. A review of the literature reveals that this procedure has only once before been described in a 1975 report by Smith and Payne.8 Their patient underwent similar reconstruction and also had complete relief of symptoms. Whether the reason this procedure has not been more universally adopted is due to the relative infrequency of this problem or due to this option being overlooked is unclear, although it is the author’s opinion that it is more likely the latter.

The technical aspects of this procedure are relatively straightforward and are described in case 1 and outlined in Figs. 1- 3. The main tenets are to accurately dissect out the pyloroduodenal junction along its serosal layer with care taken to preserve the gastric blood supply (the right gastroepiploic artery and the right gastric artery). The junction is divided on the duodenal side to avoid any potential for retained stomach/antrum. The biliary limb should be divided approximately 15 cm distal to the ligament of Treitz and anastomosed approximately 45 cm distal to the pyloric division.

Conclusion

Severe medically refractory duodenogastric reflux is fortunately relatively rare after esophagectomy. When encountered, however, it is extremely debilitating for the patient, and surgical options have centered on resection of the conduit with colonie or jejunal reconstruction, a major undertaking with a significant morbidity profile. The cases described show that construction of a Roux-en- Υ limb to the gastric conduit, a much simpler operation with lower potential morbidity, can safely and effectively relieve severe duodenogastric reflux after esophagectomy.

REFERENCES

1. Orringer MB, Marshall B, Iannettoni MD. Eliminating the cervical esophagogastric anastomotic leak with a side-to-side stapled anastomosis. J Thorac Cardiovasc Surg 2000;119:277-88.

2. Hulscher JB, van Sandick \JW, de Boer AG, et al. Extended transthoracic resection compared with limited transhiatal resection for adenocarcinoma of the esophagus. N Engl J Med 2002;347: 1662-9.

3. Rentz J, Bull D, Harpole D, et al. Transthoracic versus transhiatal esophagectomy: a prospective study of 945 patients. J Thorac Cardiovasc Surg 2003; 125:1114-20.

4. Aly A, Jamieson GG. Reflux after oesophagectomy. Br J Surg 2004;91:137-41.

5. Shibuya S, Fukudo S, Shineha R, et al. High incidence of reflux esophagitis observed by routine endoscopic examination after gastric pull-up esophagectomy. World J Surg 2003;27:580-3.

6. Sawyers JL, Herrington JL Jr, Buckspan GS. Remedial operation for alkaline reflux gastritis and associated postgastrectomy syndromes. Arch Surg 1980;115:519-24.

7. Kelly KA, Becker JM, van Heerden JA. Reconstructive gastric surgery. Br J Surg 1981;68:687-91.

8. Smith J, Payne WP. Surgical technique for management of reflux esophagitis after esophagogastrectomy for malignancy. Further application of Roux-en-Y principle. May Clin Proc 1975;50: 588-90.

MARIO G. GASPARRI, M.D., WILLIAM B. TISOL, M.D., GEORGE B. HAASLER, M.D.

From the Division of Cardiothoracic Surgery, Medical College of Wisconsin, Milwaukee, Wisconsin

Address correspondence and reprint requests to Mario G. Gasparri, M.D., Division of Cardiothoracic Surgery, Medical College of Wisconsin, 9200 W. Wisconsin Avenue, Milwaukee, WI 53226.

Copyright The Southeastern Surgical Congress Aug 2005

Tailgut cysts are rare congenital lesions arising from remnants of normally regressing postanal primitive gut. They often present in middle-aged women with perirectal symptoms and a retrorectal multicystic mass. These cysts have occasionally shown malignant transformation. We report a case of a tailgut cyst occurring in a 25- year-old African-American female. The differential diagnosis of a retrorectal mass is briefly explored, and the etiology, diagnostic strategy, and surgical approach for tailgut cysts is examined. We also report an extensive literature review to examine clinical characteristics and surgical data for 43 cases of tailgut cysts spanning 16 years.

TAILGUT CYSTS, also known as retrorectal cystic hamartomas, are rare congenital lesions thought to arise from the remnants of the embryonic postanal gut. They predominantly occur as retrorectal multicystic masses in women. According to the largest case series by Hjermstad and Helwig in 1988 (n = 53),1 nearly half of the cases are asymptomatic and are frequently found on routine physical exam. When present, reported complaints include chronic perirectal pain and symptoms secondary to mass effect. Tailgut cysts occur in the company of a broad spectrum of diagnostic possibilities in the retrorectal space and, due to its rarity, the diagnosis is often delayed. Without complete excision, recurrence and infection are likely to occur. There have been 17 reported cases of malignancy arising from a tailgut cyst since 1988, further reinforcing the need for complete excision. We report a case of tailgut cyst occurring in an African-American female and review the literature.

Case Report

A 25-year-old African-American female with a previous diagnosis of recurrent perirectal abscesses presented with a 6-month history of increasing rectal pain, occasional rectal bleeding, and constipation. Two prior episodes with similar symptoms had occurred in the past, and she was treated with transrectal incision and drainage (l&D) 2 and 3 years earlier. A biopsy from an outside hospital reported no evidence of malignancy, and colonoscopy had shown compression of the anterior rectum without mucosal changes.

Physical exam revealed a moderately tender extrinsic rectal mass. CT scan showed a 9 7 cm fluid-filled cystic mass posterior to the rectum. At our institution, transrectal I&D was performed twice but failed to prevent the return of the mass and symptoms within months. Pathology from biopsy during these procedures only showed moderately inflamed dense fibrous tissue. MRI was performed (Fig. 1) and revealed a 6 7 cm trilobulated retrorectal mass displacing the rectum anteriorly. At this point, a developmental cyst was suspected, and complete surgical excision of the recurrent mass using a transsacral approach (Kraske method) was attempted.

Intraoperatively, three cystic compartments were identified with adhesions to pelvic floor musculature. Blunt and sharp dissection was used to separate the mass from the pelvic floor. The posterior lobule was entered and produced large amounts of opaque, gray fluid. The two lateral compartments were densely adhered to the fascia of the posterior rectum, and a small portion was left behind. The internal lining of the remaining portion was cauterized. Pathology from tissue obtained was consistent with a tailgut cyst and demonstrated multiple cysts lined by squamous columnar and transitional epithelium (Fig. 2). These were surrounded by dense fibrous tissue and poorly formed smooth muscle. Acute and chronic inflammation was noted, and there was no evidence of dysplasia.

The postoperative course was uneventful, and 6 months later there was no recurrence of the mass on CT (Fig. 3). One year later, the patient was without symptoms.

Discussion

The retrorectal space is a potential space developed when a mass displaces the rectum anteriorly. It is formed posteriorly by the sacrum and coccyx and anteriorly by the rectum. The pelvic peritoneal reflection forms the superior border, and the levator ani and coccygeus muscles form the inferior border. The lateral boundaries consist of the ureters and iliac vessels. 1-4

FIG. 1. Initial MRI demonstrating a well-defined multicystic mass in the retrorectal space.

The differential diagnosis of masses within this space is broad and includes primary tumors of neurogenic, osteogenic, and congenital origin, in addition to metastatic and inflammatory processes. Congenital lesions include chordomas (remnants of notochord), teratomas, anterior sacral meningoceles, and developmental cysts (dermoid, epidermoid, enteric duplication, and tailgut cysts).2, 3 Excluding inflammatory lesions, developmental cysts are the most common masses in the retrorectal space.2

Developmental cysts are distinguished by their histopathologic differences. Dermoid and epidermoid cysts are both lined with stratified squamous epithelium; however, only dermoid cysts contain dermal appendages (hair follicles, sweat glands, tooth buds). Dermoid cysts arise from faulty inclusion of ectoderm when the embryo coalesces. Epidermoid cysts are formed from inclusion of epidermal elements at the time of neural groove closure in the meninges. Rectal duplication cysts are lined by typical gastrointestinal epithelium (often with crypts, villi, and glands) and are surrounded by two well-formed layers of smooth muscle with nerve plexuses. There are several theories that speculate on their origin: persistence of fetal gut diverticula, defective recanalization of primitive gut, or a form of caudal twinning.1, 3, 5-8

Tailgut cysts (TGCs), or retrorectal cystic hamartomas, are predominantly multicystic and can contain a variety of epithelia between cysts or even within the same cyst. Epithelial types include stratified squamous, transitional, mucinous or ciliated columnar, and cuboidal mucus secreting. In contrast to enteric duplication cysts, TGCs have disorganized smooth muscle fibers within the cyst wall and do not contain neural plexuses.1-8

FIG. 2. Intraoperative photo showing trilobulated cystic structure.

FIG. 3. Medium power (100). On the left, keratin “pearls” are seen, suggesting squamous differentiation. Several cells on the right side of the field appear to contain intracellular mucin, suggesting glandular differentiation.

Defective embryological development of the hindgut region is thought to give rise to TGCs. During development, the embryo possesses a true tail containing the continuation of the primitive gut. The anus forms cephalad to the tail via invagination of the ectoderm (thus giving rise to the term “tailgut” or “postanal gut”). The remaining postanal gut is a tubular structure lined by two to four layers of stratified cuboidal epithelium. This eventually fills with epithelial debris and atrophies as the tail region regresses during the eighth week of development. The remnants of the primitive gut that fail to regress are believed to form TGCs. Origin from the neuroenteric canal has also been suggested.1, 3, 8

Middeldorpf described the first congenital cyst in the literature when he reported a presacral mass in a 1-year-old girl in 1885. In his report, he implicates a source from the tailgut but apparently describes a rectal duplication cyst. Nevertheless, many subsequent early authors referred to any presacral congenital cystic mass, most commonly teratomas, as Middeldorpf tumors.1, 3, 6, 8 Later, Peyron studied the embryonic tailgut, and in 1928 he concluded anterior sacrococygeal or retrorectal cystic masses to be of tailgut origin if their lining consisted of an intestinal-type epithelium and they lacked a definite muscular or serous coat.1, 6 In their report in 1988, Hjermstad and Helwig reinforced the stipulation of absence of a well-defined muscular wall with myenteric plexuses to exclude duplication cysts.1 Numerous terms have been used in the literature to describe these tailgut remnants, including “tailgut vestige,””postanal gut cyst,””retrorectal cystic hamartoma,” and “tailgut cyst.”

TABLE 1. Clinical Data

Hjermstad and Helwig reported the largest case series of tailgut cysts (n = 53) and described the clinical characteristics. They found TGCs presented at any age but did so predominantly in middle- age, appearing as multicystic masses in the retrorectal space. They also found a 3:1 female to male ratio. Approximately half of the patients were symptomatic, with the most common symptoms being perirectal pain and symptoms of mass effect: rectal fullness, constipation, painless rectal bleeding, change in caliber of stool or urinary frequency. In asymptomatic patients, TGCs were found on routine rectal or pelvic exam. Signs associated with TGC include draining sinuses and a funnel-shaped postanal dimple. They reported that malignancy arising from a TGC was rare with a few cases of widespread metastases and death.1

The differential diagnosis for a retrorectal mass can be narrowed using a combination of diagnostic tools to reach a preoperative diagnosis of a developmental cyst. Due to their location, almost all retrorectal tumors will be palpable on rectal examination, and developmental cysts will manifest as extrinsic masses.2, 3 Colonoscopy could rule out any rectal mucosal changes in cases of rectal bleeding. Bari\um enema can only further characterize lesions as extrinsic to the rectum and provides no additional information.2, 3 Endorectal ultrasound has been used to characterize the lesion as cystic and occasionally shows internal echoes due to mucoid or inflammatory debris.1, 3, 5, 9, 10 Radiographie workup has included plain films to rule out bone destruction indicative of metastases or osseous lesions. The main CT findings for developmental cysts are of a well-defined thin-walled cystic retrorectal mass often with compression of the posterior rectum (without invasion of rectal wall). Further, CT can identify bony destruction or calcifications indicating malignancy or solid portions of a teratoma. Rarely, thin calcifications have been reported on CT of tailgut and dermoid cysts.5, 11-13 There are limited reports of MR findings of TGCs, but they describe a retrorectal mass with hypointense T!-weighted images and hyperintense T2-weighted images. MRI has limited ability to detect calcifications but can diagnose fatty tumors using fat suppression, and sagittal films can evaluate structural relationships.11, 14, 15 The differentiation between a retrorectal component of a perineal abscess is difficult. Recurring abscesses in the retrorectal space, repeated operations for an anal fistula, or inability to locate infection sites for anal, perianal, or rectal sinus should raise suspicion for a retrorectal cyst.2, 3, 5, 14, 15

The definitive diagnosis and treatment of a TGC is through complete surgical excision. Biopsy should not be attempted (unless the mass is surgically unresectable at presentation) due to risk of spreading dysplastic cells through weakened cyst walls. In addition, tissue obtained from biopsy is often not extensive enough to show all the histologie features necessary for diagnosis.1, 3, 6, 16 Complete excision is necessary to prevent recurrence, infection, and possible malignant transformation. For most lesions, a posterior approach with removal of a portion of the coccyx will allow the best visualization and removal of the multiloculated cysts.1-3, 8 In the 188Os, a German surgeon named Kraske first described an approach to the retrorectal space. The Kraske method uses a longitudinal incision, but other posterior transsacral approaches use a transverse incision over the sacrococcygeal joint.8 In the posterior approach, the patient is in the prone jackknife position, a portion of the coccyx is removed, and a plane is defined between the posterior rectal wall and the mass.3, 4 Cysts dissected from the rectal wall benefit from a finger in the rectum for tactile feedback. Surgical scars and tracts from previous incisions and drainage should be completely excised. In the case of larger tumors, those above the sacral promontory, or when malignancy is suspected, a combined abdominal-sacral approach may be used. The retrorectal space is first approached through the abdomen, where the rectosigmoid colon is mobilized and control of the iliac vessels is accomplished. Then, a similar transsacral approach can be tried but with the benefit of vascular control and identification of structures from above.3, 4, 8

Since Hjermstad and Helwig published their findings in 1988, there have been no large case series reported. From our review of the literature (keyword = tailgut cyst or retrorectal cystic hamartoma, limits = English), there have been 43 cases with confirmed diagnosis of TGC since their report. All cases with a conclusive pathological diagnosis of tailgut cyst were included, as well as those that occurred outside the retrorectal space. Many of the previously known clinical aspects of TGCs were reinforced (Table 1). The female to male ratio was approximately 3 to 1 (33 to 10). Excluding three neonates, women and men had an average age of 43.8 and 50.1 years at presentation (t test, P = 0.43), respectively. Review of the literature revealed only one other verified case of a tailgut cyst occurring in an African-American adult. However, most studies do not clarify race, so this significance is not entirely clear. Clinical presenting signs and symptoms were also similar to previous reports, and we found 39 cases where this information was known. Twenty patients (51.3%) presented with complaints of perirectal symptoms from mass effect: pain, decreased stool caliber, constipation, fullness, rectal bleed. Seven (17.9%) complained of abdominal, pelvic, or flank pain; however, only four of these had TGCs in the retrorectal space. Six (15.4%) presented with anorectal signs (recurrent fissures, fistulas, pilonidal abscess, anal stenosis, sacral dimple). Three (7.7%) presented only with enlarging sacrococcygeal soft tissue masses: two of these patients were neonates. Earlier reports indicate that almost 50 per cent of TGCs were found on routine pelvic or rectal examinations. Interestingly, only four (10.3%) patients were asymptomatic and had their masses found on routine exams. Note that the sum of the numerators is 40 because one patient presented with both perianal pain and a recurrent anal fistula.

TABLE 2. Surgical and Follow-up Data

TGCs almost exclusively occur within the retrorectal space; however, our review showed 16.3 per cent (7/43) of the confirmed cases occurred outside the retrorectal space: two perirenal,21, 24 two subcutaneous in anorectal region.16, 20 two subcutaneous sacrococcygeal,22, 30 and one anterior to the rectum.19 The perirenal location has been theorized to be due to unregressed tailgut involvement in the path of ascending kidney development.21, 24 Seventeen cases of malignancy arising from within a TGC were found: 11 adenocarcinomas,6, 7, 11, 14,,19, 25, 25, 31, 34 5 carcinoids,20, 17, 23, 32, 37 and 1 neuroendocrine.6 There is some debate in the literature about the classification of one case of carcinoid versus neuroendocrine,23 but it has been classified as carcinoid here.

Surgical data (Table 2) from these cases were reported irregularly, but we were able to find 38 excisions of TGCs (including two recurrences) within the retrorectal space. However, only 28 cases described specific procedures. The posterior approach was used most frequently (46.4%, 13/28), and five of these were associated with malignancy. Only seven cases using the posterior approach for TGCs in the retrorectal space provided follow-up data.10, 19, 26, 29, 31, 34, 36 There were no recurrences, and disease-free survival was reported at 0.5, 12, 12, 18, 38, and 60 months and 1-5 years. A variety of other surgical approaches were used as shown in Table 2.

Seven recurrences were reported, and five of these had a known initial procedure. Three cases of TGCs with malignant degeneration had recurrence of disease. Twelve months after abdominoperineal resection of a 2-cm submucosal anorectal TGC associated with carcinoid, liver and brain metastases were discovered.20 An adenocarcinoma within a 16-cm TGC in the retrorectal space recurred with metastases at 6 months (death occurred at 14 months) after a combined abdominosacral approach.28 A 13-cm TGC with adenocarcinoma recurred at 4 years after a radial approach.7 Two cases reported recurrences of TGCs without associated malignancy after excision of the tumor within the retrorectal space: 2 years after laparotomy and 1 year after transanal excision.3, 29 There is evidence of increased morbidity associated with improper treatment, with at least four cases of multiple I&Ds that failed to prevent the return of symptoms.26, 29, 34

Tailgut cysts are rare lesions but are being reported with increasing frequency in the literature. There is a case report of a tailgut cyst causing pelvic outlet obstruction as well as being associated with a pilonidal sinus.39, 40 They present predominantly in middleaged females with perirectal symptoms as a multicystic mass located in the retrorectal space. The diagnosis is often delayed and can be difficult to distinguish from an inflammatory process. Arrival at a clinical diagnosis of developmental cyst can be achieved through a combination of history and physical exam, colonoscopy, and CT/MRI imaging. Biopsy should be avoided if possible. Complete surgical excision using a transsacral or an abdominosacral approach is necessary for diagnosis and definitive treatment. Index of suspicion should be high for women with a multicystic retrorectal mass, especially if not responding to previous attempts at incision and drainage.

REFERENCES

1. Hjermstad BM, Helwig EB. Tailgut cysts. Report of 53 cases. Am J Clin Pathol 1988;89:139-47.

2. Jao S-W, Beart RW Jr. Spencer RJ, et al. Retrorectal tumors: Mayo Clinic experience, 1960-1979. Dis Colon Rectum 1985;28: 644- 52.

3. Hannon J, Subramony C, Scott-Conner CE. Benign retrorectal tumors in adults: the choice of operative approach. Am Surg 1994;60:267-72.

4. Scott-Conner CE, Dawson DL. Operative Anatomy. Transsacral Approach to Rectal Lesions. Philadelphia: J.B. Lippincott, 1993, pp 594-8.

5. Dahan H, Arrive L, Wendum D, Docou le Pointe H, Djouhri H, Tubiana JM. Retrorectal developmental cysts in adults: clinical and radiologic-histopathologic review, differential diagnosis, and treatment. Radiographies 2001:21:575-84.

6. Prasad AR, Amin MB, Randolph TL, et al. Retrorectai cystic hamartoma: report of 5 cases with malignancy arising in 2. Arch Pathol Lab Med 2000; 124:725-9.

7. Graadt van Roggen JF, Welvaart K, de Roos A, et al. Adenocarcinoma arising within a tailgut cyst: clinicopathological description and follow up of an unusual case. J Clin Pathol 1999;52: 310-2.

8. Pyo DJ. Tailgut cyst (retrorectal cyst hamartoma): case report and review. Mt Sinai J Med 1990;57:249-52.

9. Hutton KA, Benson EA. case report: tailgut cyst-assessment with transrectal ultrasound. Clin Radiol 1992;45:288-9.

10. Thomas S, Reece-Smith H, Themen A. Modified approach to tailgut cyst excision. J R Soc Med 2000;93:275-6.

11. Liessi G, Cesari S, Pavanello M, Butini R. Tailgut cysts: CT and MR findings. AbdomImaging 1995;20:256-8.

12. Yang DM, Jung DH, Kim H, et al. Retroperitoneal cystic masses: CT, clinical, and pathologic findings and literature review. Radiographies 2004;24:1353-65.

13. Podberesky DJ, Falcone RA, Emery KH, et al. Tailgut cyst in a child. Pediatr Radiol 2005;35:194-7.

14. Eim KE, Hsu WC, Wang CR. Tailgut cyst with malignancy: MR imaging findings. AJR Am J Roentgenol 1998; 170:1488-90.

15. Kim MJ, Kim WH, Kim NK, et al. Tailgut cyst: multilocular cystic appearance on MRI. J Comput Assist Tomogr I997;21: 731-2.

16. Sidoni A, Bucciarelli E. Ciliated cyst of the perineal skin. Am J Dermatopathol 1997;19:93-6.

17. Jacob S, Dewan Y, Joseph S. Presacral carcinoid tumour arising in a tailgut cyst-a case report. Indian J Pathol Microbiol 2004;47:32-3.

18. Antao B, Lee AC, Gannon C, et al. Tailgut cyst in a neonate with anal stenosis. Eur J Pediatr Surg 2004; 14:212-4.

19. Kanthan SC, Kanthan R. Unusual retrorectal lesion. Asian J Surg 2004;27:144-6.

20. Song DE, Park JK, Hur B, Ro JY. Carcinoid tumor arising in a tailgut cyst of the anorectal junction with distant metastasis: a case report and review of the literature. Arch Pathol Lab Med 2004; 128:578-80.

21. Sung MT, Ko SF, Niu CK, et al. Perirenal tailgut cyst (cystic hamartoma). J Pediatr Surg 2003;38:1404-6.

22. Murao K, Fukui Y, Numoto S, Urano Y. Tailgut cyst as a subcutaneous tumor at the coccygeal region. Am J Dermatopathol 2003;25:275-7.

23. Mourra N, Caplin S, Parc R, Flejou JF. Presacral neuroendocrine carcinoma developed in a tailgut cyst: report of a case. Dis Colon Rectum 2003;46:411-3.

24. Kang JW, Kim SH, Kim KW, et al. Unusual perirenal location of a tailgut cyst. Korean J Radiol 2002;3:267-70.

25. Moreira AL, Scholes JV, Boppana S, Melamed J. p53 Mutation in adenocarcinoma arising in retrorectal cyst hamartoma (tailgut cyst): report of 2 cases-an immunohistochemistry/ immunoperoxidase study. Arch Pathol Lab Med 2001; 125:1361-4.

26. Yamaguchi K, Okushiba S, Katoh H, et al. Tailgut cyst invaded by rectal cancer through an anal fistula: report of a case. Dis Colon Rectum 2001;44:447.

27. Oh JT, Son SW, Kim MJ, et al. Tailgut cyst in a neonate. J Pediatr Surg 2000;35:1833-5.

28. Schwarz RE, Lyda M, Lew M, Paz IB. A carcinoembryonic antigen- secreting adenocarcinoma arising within a retrorectal tailgut cyst: clinicopathological considerations. Am J Gastroenterol 2000 ;95:1344- 7.

29. Costello D, Schofield A, Stirling R, Theodorou N. Extrarectal mass: a tailgut cyst. J R Soc Med 2000;93:85-6.

30. Rafindadi AH, Shehu SM, Ameh EA. Retrorectal cystic harmatoma (tailgut cyst) in an infant: case report. East Afr Med J 1998:75:726- 7.

31. Maruyama A, Murabayashi K, Hayashi M, et al. Adenocarcinoma arising in a tailgut cyst: report of a case. Surg Today 1998;28:1319- 22.

32. Horenstein MG, Erlandson RA, Gonzalez-Cueto DM, Rosai J. Presacral carcinoid tumors: report of three cases and review of the literature. Am J Surg Pathol 1998;22:251-5.

33. Roche B, Marti MC. Tailgut cyst, an unusual evolution. Swiss Surg 1997;3:21-4.

34. Levert LM, Van Rooyen W, Van Den Bergen HA. Cysts of the tailgut. Eur J Surg 1996;162:149-52.

35. Fujitaka T, Nakayama H, Fukuda S, et al. A tailgut cyst found accompanying rectal cancer: report of a case. Surg Today 1995:25:65- 7.

36. Gips M, Melki Y, Wolloch Y. Cysts of the tailgut. Two cases. Eur J Surg 1994:160:459-60.

37. Lin SL, Yang AH, Liu HC. Tailgut cyst with carcinoid: a case report. Zhonghua Yi Xue Za Zhi (Taipei) 1992:49:57-60.

38. McDermott NC, Newman J. Tailgut cyst (retrorectal cystic hamartoma) with prominent glomus bodies. Histopathology 1991; 18:265- 6.

39. Smyrniotis V, Kehagias D, Paphitis A, et al. Tailgut cysts: a rare cause of pelvic outlet obstruction. Eur J Gynaecol Oncol 2001;22:74-6.

40. Satyadas T, Davies M, Nasir N, et al. Tailgut cyst associated with a pilonidal sinus: an unusual case and a review. Colorectal Dis 2002:4:201-4.

CHRISTOPHER KILLINGSWORTH, M.D., THOMAS R. GADACZ, M.D.

From the Department of Surgery, Medical College of Georgia, Augusta, Georgia

Presented at the Annual Scientific Meeting and Postgraduate Course Program, Southeastern Surgical Congress, New Orleans, LA, February 11-15, 2005.

Address correspondence and reprint requests to Thomas R. Gadacz, M.D., Department of Surgery, Medical College of Georgia, 1120 15th Street, Augusta, GA 30912.

Copyright The Southeastern Surgical Congress Aug 2005

Malignant transformation is an infrequent complication of endometriosis. The ovary is the primary site in 79 per cent of cases, and extragonadal sites are identified in 21 per cent. Primary involvement of these types of tumors with the colon and/or rectum is a rare clinical entity. Endometrioid carcinoma is a common histologic type that remains a diagnostic challenge-the main differential diagnosis includes colorectal carcinomas. We report a case of malignant transformation arising in colonic endometriosis. The patient had a total abdominal hysterectomy and bilateral salpingo-oophorectomy 10 years before she presented with hematochezia. The patient was ultimately treated by surgical resection. Immunohistochemical staining in addition to the usual histopathology was critical for accurate diagnosis of this endometriosis-associated intestinal tumor.

ENDOMETRIOSIS IS A COMMON benign gynecologic condition affecting about 10 per cent to 25 per cent of women evaluated for gynecologic complaints in the United States.1, 2 Intestinal endometriosis occurs in 3 per cent to 37 per cent of reported cases, typically involving areas where the peritoneum is irregularly folded such as the rectovaginal septum, rectum, and sigmoid colon.3 Malignant transformation of endometriosis is a rare but clinically significant complication, occurring in up to 1 per cent of women.4 The ovary is the primary site in about 79 per cent of known cases, and extragonadal pelvic sites (rectovaginal septum, vagina, omentum, umbilicus, broad ligament, ureter, vesicovaginal septum, etc.) represent about 21 per cent.5 The colon and/or rectum are involved in only 5 per cent of cases.6 In this article, we present a case of endometrioid adenocarcinoma of the rectosigmoid colon wall, originally diagnosed as a rectal cancer.

Case Report

A 60-year-old woman (gravida 4, para 3), who had undergone a total abdominal hysterectomy and bilateral salpingo-oophorectomy 10 years earlier because of extensive endometriosis, presented with hematochezia. She was otherwise asymptomatic. Her past medical history was remarkable for type 11 diabetes and hypothyroidism. Her father had a history of colon cancer in his 60s, and her grandfather had an undefined gastrointestinal tumor. No other family members had colorectal or endometrial neoplasms. She was taking oral estrogen replacement (Premarin).

The patient underwent colonoscopy, which revealed a 3.5 to 4 cm sessile polyp on the anterior rectal wall, which was partially excised (Fig. 1). Pathology revealed a moderately differentiated adenocarcinoma presumably of rectal origin. Subsequent computed tomography scan showed no evidence of metastatic disease. She was referred to our institution for definitive therapy. Flexible sigmoidoscopy and rigid proctoscopy revealed a small focus of residual tumor (

Gross pathologic review of the specimen revealed a 2 cm^sup 3^ mural mass extending through the muscularis propria of the upper rectum into the perirectal fat. Histologic review showed areas of benign endometriosis (bland endometrioid glands and associated stroma) as well as foci of well-differentiated endometrioid adenocarcinoma (FIGO grade I of III) over the entirety of the rectal wall mass (Fig. 2). A total of nine mesenteric lymph nodes were examined but did not reveal any evidence of malignancy. In the context of these findings, re-review of the original colonoscopic biopsy specimen showed that its morphology was identical to the present rectal wall tumor. Immunoperoxidase stains were used to confirm the mullerian origin of the tumor. A CDlO stain was used because it selectively highlights endometrial stroma in areas of endometriosis and of adenocarcinoma. The tumor cells were positive for CA-125 and negative for carcinoembryonic antigen. When the keratin subtypes were examined, the tumor displayed an endometrial phenotype with positive cytokeratin 7 and negative cytokeratin 20 (Fig. 3). In contrast, cells of gastrointestinal origin show the opposite immunophenotype: negative cytokeratin 7 and positive cytokeratin 20.7 Overall, the immunostaining pattern from our panel of tumor markers is highly specific for endometrioid adenocarcinoma. The final pathologic diagnosis was primary endometrioid adenocarcinoma arising in rectal wall endometriosis. Pathologic specimens from the patient’s hysterectomy and oophorectomy specimen 10 years earlier were subsequently reexamined and found to contain only benign endometriosis.

FIG. 1. Colonoscopic view of a sessile polyp. A large sessile polyp of the colorectum is shown located in the anterior colon wall (black arrow).

Discussion

Since 1925, when Sampson first described the phenomenon of malignant transformation of endometriosis (both in gonadal and extragonadal sites), a steadily growing number of cases have been reported.5 A subset of these cases had gastrointestinal tract involvement and were classified as endometriosis-associated intestinal tumors (EAITs).8 Because colorectal cancer is far more common than EAIT, it is not uncommon for these tumors to be confused with colorectal carcinoma. Diagnosis of EAIT is based on the following classic criteria: tumor cells arising in benign tissue (not invading from another source), the presence of tissue resembling endometrial stroma surrounding epithelial glands, and microscopic endometriosis contiguous with the malignant tissue. In our case, additional histologie techniques were used to confirm the gynecologic origin of this tumor.

FIG. 2. Microscopic views of endometrioid adenocarcinoma. Top panel: A hematoxylin and eosin-stained low-magnification, cross- sectional view encompassing the colonie tumor mass and layers of colon wall is shown. Bottom panel: An enlarged view of tumor cells is shown from the white box inset. Tumors cells have a mucosal location and are polypoid in shape, thus mimicking the more common colon adenocarcinomas.

EAIT is an extremely rare tumor, and the current case represents only the 19th report of a primary EAIT and 10th report where the patient was using unopposed estrogen.9 All 19 cases of primary adenocarcinomas, to date, occurred at the rectosigmoid colon, likely as a consequence of this anatomic location having the highest incidence of endometriosis.10,11 These tumors typically occur in women from age 30 to 60 years, earlier than most colorectal cancers. The most common signs and symptoms are abdominal and/or pelvic pain, pelvic mass, vaginal bleeding, or bloody stools. However, these tumors are often discovered incidentally as serosal nodules during surgical exploration for other reasons.12 Less commonly, patients may present with small or large bowel obstruction resulting from a mass or an acute abdomen secondary to acute appendicitis,13 intussusception,14 or perforation.15

FIG. 3. Immunostaining of tumor mass reveals a mullerian origin. Cytokeratin (CK) immunostaining was performed. Tumor cells of interest are highlighted (black arrow) and show an endometrial phenotype, staining positive for CK7 and negative for CK20.

On gross exam, endometriosis usually involves the serosa and subserosa (up to 70%8), although involvement of the deeper bowel layers (muscularis propria, submucosa, or even mucosa) may be seen in symptomatic patients.5 Tumors arising in endometriosis are predominantly limited to their site of origin of the benign disease. Transmural tumors show a typical dumbbell shape characterized by a bulky serosal and polypoid mucosal tumor connected by a narrower neoplastic waist that extends through muscle bundles of the muscularis propria.8 The most common histologie subtype is endometrioid adenocarcinoma of low to intermediate grade,5 sometimes with squamous differentiation. Other less common histologie types include sarcoma, clear cell, squamous cell, or mixed germ cell.

Histologie examination of superficial, endoscopie biopsy material may be difficult to assess definitively for multiple reasons. The limited amount of specimen available may not contain diagnostic endometriotic glands and stroma. Nonspecific, chronic changes may be seen and misinterpreted as other pathologies such as inflammatory bowel disease16 or solitary rectal ulcer syndrome.17 In other instances, the tumor may have overgrown the tissue of origin (endometriosis), completely destroying it and thus mimic a primary colon carcinoma.5 Finally, the mucosa is frequently normal or shows minimal changes if sampled endoscopically because endometriosis usually involves the outer bowel wall.

Endometrioid adenocarcinoma is the EAIT most likely to be confused with a colorectal carcinoma, as was the case for our patient. Primary colon carcinoma always involves the bowel mucosa and may be associated with adenomatous changes or a neoplastic polyp. Advanced colon carcinomas may extend from the mucosa throughthe bowel wall and to the serosal surface or adjacent fat. In contradistinction, endometriosis and cancers arising in it show the opposite pattern of growth in the bowel, arising in an extramural location and invading into the bowel wall from the outside. Endometrioid carcinomas typically form tubular glands with “clean” luminal contents. Their neoplastic cells lack mucin and have an Alcian blue-positive glycocalyx. The key morphologic feature, obviously, is the presence of a background of benign endometriosis to differentiate endometrioid adenocarcinoma from colon carcinoma. Despite these criteria to identify EAIT, the practical reality of accurate diagnosis is difficult especially with poorly differentiated tumors. To prevent possible diagnostic errors, we recommend the routine use of immunochemistry in all cases of EAIT for confirmation. The suggested minimal number of markers required is 2, corresponding to the cytokeratin subtypes 7 and 20.7 In a study of 165 tumors, 86 per cent of the endometrioid tumors and none of the colorectal carcinomas showed a positive cytokeratin 7, negative cytokeratin 20 immunostaining pattern, whereas 96 per cent of the colorectal carcinomas and none of the endometrioid tumors showed a negative cytokeratin 7, positive cytokeratin 20 pattern.18

Exogenous estrogen is widely accepted as a contributing factor in the development of premalignant or malignant transformation of endometriosis.19’20 In their review of the literature, Jones et al.9 reported nine cases of primary EAIT arising in the rectosigmoid colon in patients using unopposed estrogen for several years prior to the development of cancer. They concluded that their findings supported a causal, cancercausing role for unopposed estrogen. This has led some authors to recommend a routine short course of a progestin to suppress residual endometriosis before the initiation of estrogen replacement.5,21 Malignancy associated with hyperestrogenism correlated most frequently (69%) with well- differentiated adenocarcinomas.20 Overall, the prognosis for estrogen-stimulated EAIT arising in any gastrointestinal site is highly favorable with a survival rate of 82 per cent at 5 years.5

Treatment for this disease has been variably reported in the literature and is highly individualized. In most cases of nonmetastatic EAIT, if feasible, primary surgical treatment with complete resection of all dis ease should be performed. General indications for surgery include pain, bleeding, altered bowel habits, and intestinal obstruction.22 The therapeutic value of chemoradiation for metastatic EAIT is of unclear value.5 The situation is similar in the adjuvant setting after complete resection of disease because of only sporadic reports.12

In summary, EAIT is a rare but clinically significant disease predominantly affecting postmenopausal patients. Clinical suspicion should arise in patients previously treated for endometriosis who later present with abdominal pain or rectal bleeding, especially in those who have received unopposed estrogen hormone replacement. These tumors can be diagnostically challenging because they can resemble common primary neoplasms of the gastrointestinal tract both clinically and pathologically. More frequent use of confirmatory immunohistochemical panels may reveal that the incidence and prevalence of malignant transformation in endometriosis may be higher than current estimates. Awareness and recognition of these types of tumors by surgeons, therefore, may result in better overall care to affected patients.

REFERENCES

1. Henriksen B. Endometriosis. Am J Surg 1955:90:331-7.

2. Ranney B. Endometriosis. 3. Complete operations. Reasons, sequelae, treatment. Am J Obstet Gynecol 1971:109:1131-44.

3. Mourra N, Tiret E, Parc Y, et al. Endometrial stromal sarcoma of the rectosigmoid colon arising in extragonadal endometriosis and revealed by portal vein thrombosis. Arch Pathol Lab Med 2001; 125:1088-90.

4. Corner GW, Hu CY, Hertig AT. Ovarian carcinoma arising in endometriosis. Am J Obstet Gynecol 1950:59:760-74.

5. Heaps JM, Nieberg RK, Berek JS. Malignant neoplasms arising in endometriosis. Obstet Gynecol 1990;75:1023-8.

6. Irvin W, Pelkey T, Rice L, Andersen W. Endometrial stromal sarcoma of the vulva arising in extraovarian endometriosis: a case report and literature review. Gynecol Oncol 1998;71:313-6.

7. Han AC, Hovenden S, Rosenblum NG, Salazar H. Adenocarcinoma arising in extragonadal endometriosis: an immunohistochemical study. Cancer 1998;83:1163-9.

8. Slavin RE, Krum R, Van Dinh T. Endometriosis-associated intestinal tumors: a clinical and pathological study of 6 cases with a review of the literature. Hum Pathol 2000;31:456-63.

9. Jones KD. Owen E, Berresford A, Sutton C. Endometrial adenocarcinoma arising from endometriosis of the rectosigmoid colon. Gynecol Oncol 2002:86:220-2.

10. Rowland R. Langman JM. Endometriosis of the large bowel: a report of 11 cases. Pathology 1989;21:259-65.

1 1. Tedeschi LG, Masand GP. Endometriosis of the intestines: a report of seven cases. Dis Colon Rectum 1971;14:360-5.

12. Yantiss RK, Clement PB, Young RH. Neoplastic and preneoplastic changes in gastrointestinal endometriosis: a study of 17 cases. Am J Surg Pathol 2000;24:513-24.

13. Mittal VK, Choudhury SP, Cortex JA. Endometriosis of the appendix presenting as acute appendicitis. Am J Surg 1981;142: 519- 21.

14. Mann WJ, Fromowitz F, Saychek T, et al. Endometriosis associated with appendiceal intussusception. A report of two cases. J Reprod Med 1984:29:625-9.

15. Ledley GS, Shenk IM, Heit HA. Sigmoid colon perforation due to endometriosis not associated with pregnancy. Am J Gastroenterol 1988;83:1424-6.

16. Langlois NE, Park KG, Keenan RA. Mucosal changes in the large bowel with endometriosis: a possible cause of misdiagnosis of colitis? Hum Pathol 1994;25:1030-4.

17. Daya D, O’Connell G, DeNardi F. Rectal endometriosis mimicking solitary rectal ulcer syndrome. Mod Pathol 1995;8: 599- 602.

18. Loy TS, Calaluce RD, Keeney GL. Cytokeratin immunostaining in differentiating primary ovarian carcinoma from metastatic colonie adenocarcinoma. Mod Pathol 1996;9:1040-4.

19. Reimnitz C, Brand E, Nieberg RK, Hacker NF. Malignancy arising in endometriosis associated with unopposed estrogen replacement. Obstet Gynecol 1988;71:444-7.

20. Granai CO, Walters MD, Safaii H, et al. Malignant transformation of vaginal endometriosis. Obstet Gynecol 1984;64: 592- 5.

21. Duun S, Roed-Petersen K, Michelsen JW. Endometrioid carcinoma arising from endometriosis of the sigmoid colon during estrogenic treatment. Acta Obstet Gynecol Scand 1993;72:676-8.

22. Bartkowiak R, Zieniewicz K, Kaminski P, et al. Diagnosis and treatment of sigmoidal endometriosis-a case report. Med Sci Monit 2000;6:787-90.

CHUONG D. HOANG, M.D.,* ADAM K. BOETTCHER, B.S.,* JOSE JESSURUN, M.D.,[dagger] STEFAN E. PAMBUCCIAN, M.D.,[dagger] KELLI M. BULLARD, M.D.*,[dagger]

From the Departments of * Surgery and [dagger] Laboratory Medicine and Pathology, University of Minnesota Medical School, University of Minnesota, Minneapolis, Minnesota

Address correspondence and reprint requests to Kelli M. Bullard, M.D., University of Minnesota, MMC 450, 420 Delaware Street S.E., Minneapolis, MN 55455.

Copyright The Southeastern Surgical Congress Aug 2005

Sometimes less is more.

That is a difficult concept to grasp, particularly when you are a 3-year-old. But psychologists have discovered something that helps ““ symbols.

Researchers investigating how self-control develops in children found that abstract symbols can lead the youngsters toward a more optimal decision than when they have to make a choice with tangible objects such as candy.

This was demonstrated when the researchers gave 3-year-olds the choice of a tray with two pieces of candy or one with five. Even when told that the tray they picked would be given away, most of the youngsters still picked the tray with the most candies.

However, when abstract symbols, such as dots or animal pictures were used to represent the candy, many of the 3-year-olds caught on and chose the symbol representing the smaller amount of candy, leading to the larger reward.

“Many 3-year-olds are compelled to point to larger rewards even though in this game that means they will get a smaller reward. When you remove the real reward and substitute it with symbols, it enables children to control their response,” said Stephanie Carlson, a University of Washington associate professor of psychology and lead author of a new study appearing in the current issue of the journal Psychological Science.

“When children get stuck on a problem, using symbols can help them solve it. For example, if you are trying to get kids to wait for a marshmallow as a reward it is helpful to get them to think about the reward in a different way ““ such as thinking of the marshmallow as a fluffy cloud to help them delay gratification. Many parents, however, tend to do the opposite. They say, ‘you can’t have it now, but just think about how good it will taste when you can.’ This increases the temptation instead of shifting their attention,” she said.

Carlson, who is studying executive functioning, or how children develop the ability to control their thoughts and actions, set up two experiments.

The first showed that this ability is directly related to age and verbal ability. In the experiment, 101 typically developing 3- and 4-year-olds had to make the choice between the trays containing either smaller or larger amounts of candy (jellybeans or chocolate chips). An experimenter explained the rules, and showed each child that when they pointed to a tray the candy would go to a toy monkey and the child would get the contents on the other tray. Each child was given 16 test trials, with candy being replaced on the trays after each trial.

Four-year-olds significantly outperformed the 3-year-olds, although some of the 3-year-olds with high verbal ability scored well. The 3-year-olds did not improve over the course of the trials while 4-year-olds showed significant learning.

“Three-year-olds tended to be inflexible and didn’t seem to improve with the feedback of seeing the toy monkey getting more treats,” said Carlson. “But 4-year-olds changed strategies and appeared to learn from feedback without any explicit instruction.”

In the second experiment, the researchers tested 128 typically developing 3-year-olds. The children were randomly assigned to one of four conditions ““ real treats, rocks, dots and one called mouse vs. elephant. In this experiment, two boxes with drawers containing two or five candies replaced the trays. In the first two conditions, a number of the candy or rocks corresponding to candy inside the drawers were placed on top of the boxes. In the dot condition pictures with a small or large number of dots were placed atop the boxes. In the mouse vs. elephant condition pictures of those animals were placed on the boxes and the children also were shown a stuffed toy mouse and elephant and told they had a small or large stomach that could hold a few or a lot of candies. In each case the researchers made sure the children understood that what was on top of each box corresponded to the two or five candies inside the drawers.

Then, as in the first experiment, the children were told to pick one of the two boxes, with candies inside the one they chose going to a toy monkey. Each child was given 16 trials.

There were significant performance differences depending on what was on top of the boxes. With the candies and the rocks, most of the children continued to pick the boxes with the larger amounts on top, just as the 3-year-olds in the first experiment did. But in the dots and mouse vs. elephant conditions, the children picked the boxes representing the smaller amount of candy significantly more often. And their performance was strongest in the most abstract conditions, mouse vs. elephant.

Carlson said the substitution of the real reward with symbols allowed the children to control their responses. Faced with the rock choice they “were compelled to pick the large number because the rocks had a one-to-one correspondence with the real treat.” She said with the dots there was no resemblance to the treats, just lots or less dots, and amounts were totally eliminated in the choice between the mouse and elephant. The 3-year-olds performance on the mouse vs. elephant choice matched the performance of the 4-year-olds in the first experiment.

There were no differences in the performance by boys and girls in the two experiments.

Carlson said a big jump in children’s self-control typically occurs between 3 and 4, along with other major related developmental changes such as the ability to understand another person’s perspective and to engage in elaborate pretend play.

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A RECENT report in The Lancet concluded that homeopathy was ineffective. Julia de Vaatt died a year ago from breast cancer after rejecting conventional medical treatment in favour of alternative remedies.

Here her husband Bob, 58, a former IT consultant turned novelist from West London, tells GILL SWAIN why he believes these are not merely useless, but dangerous in the way they encourage false hope.

BY THE time Julia told me she’d found a lump in her breast she’d already had a biopsy. The results had arrived that morning: it was malignant. Naturally, we were extremely upset. She was only 47 and still the girl with the wonderful smile who had bewitched me the instant we met in a London pub 12 years previously.

We married within five months, had two children and, the usual ups and downs, had been very happy.

At her next appointment, she was told she needed an immediate lumpectomy followed by chemotherapy, but she was already against it.

She had heard horror stories that once the knife goes in, cancer spreads.

It’s an old wives’ tale, but a commonly held view. I pleaded with her to have the operation for the sake of our son and daughter, then aged six and 11, and she could take complementary remedies later.

But she was adamant, so I thought I had to support her in whatever she wanted to do.

She told me that a homeopath, the wife of a business associate of mine, had had a lumpectomy two years before, but said if she could have her time again she would not have had surgery.

She believed homeopathy cured everything and, it seems to me, convinced Julia, too.

As I looked into homeopathy I developed a grudging acceptance that there might be something to it. It seemed to work on the same principle as a flu jab and the disagreement between homeopaths and the medical establishment lay in the degree of dilution of the active ingredient.

Julia could be obstinate and I never felt I could force her to do anything.

She didn’t even waver when her GP banged on our door after discovering she had refused surgery. The doctor was so exasperated that she told Julia she’d be dead in five years.

But Julia went ahead and consulted the homeopath, who had a practice in West London, once a week. After she died, I found drawers stuffed with packets and bottles of little white pills, all of which looked exactly the same but were marked liver, spleen, kidney, and so on.

There never seemed to be any tangible benefits from the homeopathy, which is probably why Julia started trying more extreme treatments.

Before long she was consulting a second homeopath, a follower of a famous Indian guru Sai Baba, who called herself Mrs Sai. She operated from a terraced house in West London.

Every Saturday I drove to the house to collect phials of pills, costing Pounds 7 each. After spending several thousand pounds over three years, I got so frustrated I asked the practitioner when we might expect a cure.

SHE replied: ‘Your wife is already cured. She doesn’t have cancer any more.’

When I told Julia this, she was so furious she threw out everything connected with Sai Baba.

By far the most useless, and most expensive, therapy was Vita Fons II water which she ordered from a company based in Taunton, Somerset, at a cost of Pounds 18 for 85ml, which I worked out as about Pounds 210 a litre.

She would order it once or twice a month with other products such as talcum powder, skin cream and even rooting powder and seed dressing for plants.

There was no list of ingredients and they all cleverly state they have no medical properties – the water even clearly states ‘this is water’.

The accompanying literature says the products have been ‘encoded with numinous development’, whatever that means, and that the preparations ‘achieve their effect by arousing awareness of an inherent perfection. Their use improves the interface between the spirit and the intrinsic divinity’.

The Vita Fons II company also offered a ‘backup service’ in which, after you send them a lock of hair so they can access your ‘unique vibrations’, they promise to ‘broadcast numinous energy’ 24 hours a day for Pounds 29.50 a month. They even charged Pounds 8 for personal letters.

This gobbledegook is supposed to be about God, but seems to me merely snake oil for the 21st century. You can neither prove nor disprove that they have any effect because it is all about the spiritual.

After she died in July 2004, I found a stash of letters which indicated to me that the woman behind Vita Fons II, Elizabeth Buckingham knew Julia had cancer. One, dated August 2003, said: ‘Have you thought of washing the wound with salty water, and quite obviously I would recommend that you add Vita Fons II to the water.’ Reading them made me ill as I realised they were telling her: splash this water over you and send another cheque please.

Using faith for commercial purposes in this way is immoral and obscene. If a parish priest tried to sell Holy Water for Pounds 210 a litre, he would be arrested.

But if you go down the alternathrough

tive route, almost anything is fair game.

Julia consulted a psychic surgeon and three or four ‘distance’ healers who talked to her on the phone without feeling the need to physically examine her; they ‘scanned’ her from their own homes at Pounds 60 per 90-minute session.

If you say you don’t feel better, they throw the blame on you for not being a good subject. For a willing patient, however, it is like a kind of club where everyone appears to pull together – though I think the patient is taken advantage of.

Once Julia had set off on the slippery slope, other practitioners swarmed in like parasites, I presume because they pass on details of customers. Some may be well intentioned, but they are making money out of vulnerable people.

By about four years after the diagnosis, in 1994, Julia was devoting her whole life to these therapies.

She shut herself in her bedroom meditating, reading or surfing the internet, while I did the shopping and cooking.

Meanwhile, the tumour was growing. It came to the surface in 2001 and there was bleeding – the Vita Fons II people said this could be a good thing or a bad thing and advised her to spray the water on her clothes so she wouldn’t have to suffer the pain of getting undressed.

She was in continuous pain in her joints and felt a stretching and tearing if she moved her arms. And the tumour started to smell – a smell of death.

It must have been hellish, yet she didn’t have a death wish. She very much wanted to be alive to be with our children, but she decided not to tell them about her illness.

People ask me why I didn’t drag her back to the doctor, but she would only have gone, literally, kickingand screaming. The more I suspected the treatments were rubbish and begged her to change her mind, the more defensive she became.

We were having financial problems as the cost of these items was getting out of control. Eventually, we were arguing so much that it was affecting our son.

I was incredibly angry with her while still trying to be supportive. I still loved her, but I decided I had to leave for my son’s sake and also to try to force her hand because we couldn’t continue the way we were.

Since she died I’ve asked myself if I feel guilty and I have to say no. I don’t know what more I could have done, but I was a lone voice against all these people she was talking to, several of whom were suggesting I was part of the problem.

I had been made redundant after 30 years in IT and went to live in a squalid bedsit, visiting the children, who stayed in the family home with her, every weekend.

I last saw Julia alive in May last year in the street with bags of shopping.

I had the feeling then that she had come to the end of her permutations.

Her final decline was swift. In July, our son left for a holiday with his friends and that same afternoon someone called the Macmillan nurses. Two days later they called me and told me to fetch our son to see his mother before she died.

HOWEVER, before I arrived I learned it was already too late and I had to tell him not only that she had cancer, but that she had gone. I don’t understand why she refused to tell the children.

Maybe she believed she would recover. I thought it was a mistake, but she was a strong-willed woman and I didn’t feel I could defy her wishes.

It was harrowing when our son burst into tears and said: ‘I knew something was wrong.’ Both he and my daughter were angry she hadn’t told them. She’d left it too late to say goodbye or even to leave them a letter to explain. I was devastated, even though we didn’t get on towards the end.

After the funeral I found dozens of boxes of the Vita Fons II water hidden in her wardrobe and also a small pill box with two white tablets and a piece of paper saying: Berlin Wall. Toxic. Do Not Touch.

This is a homeopathic remedy containing minute fragments of the actual Berlin Wall, which is supposed to help people with a lot of conflict in their lives. I have no idea how it is supposed to treat women with breast cancer. I also found credit card bills for more than Pounds 12,000 which was only a fraction of what she must have spent over the ten years of her illness.

I feel angry, but not with Julia. I’m angry with those I believe exploited her deepest fears. All these people are allowed to operate because there is no regulatory system, and their claims are so amorphous.

It is mumbo jumbo, but when you are terminally ill you can come to believe it. I think Trading Standards bodies should take a closer look. But I don’t know what they can do when someone is basically claiming to sell ‘God in a jar’. I think these people should be exposed for making a fortune out of something that is morally and ethically sick.

Homeopathy is different because it claims to be a physical treatment – and for anybody to be allowed to treat people without medical training makes no sense.

If homeopathy is legitimised, it should only be in addition to a conventional medical qualification.

Also, administering anything which purports to heal without a physical diagnosis is wrong.

I believe practitioners should acknowledge that there’s a point where alternative methods not only fail, but can become dangerous – and that point comes when they are being used by someone like Julia instead of conventional treatment.

They have a responsibility to people who may not be acting in their own best interests.

Statistics say that 85 per cent of lumpectomies are successful, so Julia had a good chance of being cured. Even if she hadn’t been, she could have lived those ten years without her terrible obsession with so-called treatments.

She would have suffered a lot less pain, family life would have been more normal, we wouldn’t have had financial pressures, and would probably not have split up. It was a terrible waste of her life.

ELIZABETH Buckingham, spokeswoman for Vita Fons II says: ‘I DON’T recognise the name of Julia de Vaatt so I am not sure if she was a customer or not.

‘What I can say is that we do not exploit people who are vulnerable and facing life and death situations. We do not promote this product as a cancer treatment or as a way to treat any physical complaint. It is recommended as a treatment for spiritual healing.’ THE British Homeopathy Association represents medically qualified homeopathic practitioners. A spokesman says: ‘THIS sounds like a tragic case and we in no way condone what has happened.

Mrs de Vaat should never have been advised that she should rely on homeopathy to cure her breast cancer.

‘We represent 1,400 homeopaths and they are all medically qualified.

None would ever suggest that a patient stops using conventional treatments after a cancer diagnosis. Homeopathy may be used alongside it.

‘Unfortunately, not all homeopaths are medically qualified and there is no statutory regulation.

This means anyone can set up as a homeopath without scrutiny.’ To check a practitioner is listed in the Faculty of Homeopaths, visit www.trusthomeopathy.org or phone the helpline: 0870 444 3950.

BOB de Vaatt is the author of Fake Honesty, published by SeaNeverDry Publishing, Pounds 7.99.

Girls are naturally 60% fatter than boys by the age of 18, researchers said yesterday.

A two-year study of almost 2,000 children aged five to 18 used a technique to measure both total body mass and body fat to see how fat levels changed as youngsters get older.

The researchers found that on average, by the age of 18, 15.4% of boys’ body mass was fat compared with 24.6% in girls.

They said that as children grew up, girls continued to gain fat after puberty, while boys gained more muscle and lean tissue.

It is hoped the new body fat reference curves, developed using bioelectrical impedance analysis (BIA) technology, will help give more accurate indications of obesity than body mass index (BMI) which looks at weight compared to height.

Professor Andrew Prentice, from the London School of Hygiene and Tropical Medicine, said that currently around 25% of children could be misclassified as either overweight or of normal weight because BMI did not differentiate between fat and muscle. He said that as it stood, a very fit and muscular youngster could be classified as obese.

‘BMI measures weight, it does not measure body fat and it is the body fat that is causing tissue damage and raising blood pressure and the risk of diabetes,’ he said.

Researcher Dr David McCarthy of London Metropolitan Univer- sity, said the gender difference they found confirmed a ‘normal biological phenomenon’ – that girls have a greater proportion of body fat for reproduction.

Green tea, steeped in an ancient civilization, conquered the West because of its supposed health effects. Wine, particularly red wine, is a relative newcomer to the health scene. Tea leaves and red grapes are said to line the path to a long and healthy life. The evidence, however, is not convincing.

Hot infusions of the leaves of Camillia sinensis have been used in China for “thousands of years,” supposedly discovered by emperor Shen-Nung in 2737 B.C. He accidentally dropped a few leaves into boiling water, and the warm drink made him feel better. Tea drinkers outside Asia prefer black tea, made by roasting and fermenting the leaves. Tea contains caffeine, which stimulates the central nervous system. It is also a diuretic and a respiratory stimulant. That a warm cup of tea can “perk you up” has a firm physiological basis. This is also true for other caffeine-containing stimulants, like coffee or cocoa, but tea boasts that romantic history of an ancient emperor fumbling with tea leaves and hot water.

Initially, green tea became important in human health because of the stimulating effect of caffeine; the emperor did not know about antioxidants. Today, antioxidants in tea, particularly green tea, are said to protect us from cancer. Why? Notwithstanding high rates of cigarette smoking, the teadrinking Chinese have one of the lowest lung cancer rates in the world.

But what about the other killer, heart disease? Green tea research makes no mention of our hearts at all. Well, it appears we just have to drink more. Red wine this time, another beverage rich in antioxidants. That is because of the French. They eat a rich diet with butter and creamy cheeses like Camembert and Brie, and according to a French diet writer, few or no vegetables (Montignac 1998). Yet the French enjoy the lowest rate of heart disease among Western countries. Apparently, this so-called French Paradox is explained by the French custom of drinking wine with their meals (Renaud and de Lorgeril 1992).

The wine antioxidants occur mostly in grape skin, so only red wine, which is fermented “on the skin,” will do. However, the antioxidants in green tea are close chemical relatives of the antioxidants in red wine. So the real paradox is this: antioxidants in green tea specifically protect the Chinese from lung cancer while other, very closely related antioxidants in red wine specifically protect the French heart. Obviously we must drink both green tea and red wine. And, according to other nutrition authorities, we already need three glasses of milk and six glasses of water a day. This could give a whole new meaning to “being on a liquid diet.” The question is, how solid is the evidence?

Antioxidants

There is no question about the antioxidant properties of some green tea constituents like epigallocatechol gallate (EGCG). Like many other plant extracts, green tea inhibits growth of cancer cells in the lab and in some rodents, but studies on humans are quite inconclusive. In fact, a meta-analysis of some thirty studies mentions several reports that link green tea consumption with an increased incidence of some cancers (Bushman 1998).

On the other hand, the French Paradox has become a popular overlay on the picture of the much-studied Mediterranean diet, which is rich in antioxidant-containing vegetables, like cabbage and tomatoes, unsaturated fats like olive oil, and wine (Matalas et al. 2001). This diet is said to decrease the incidence of heart disease and promote longevity. The French Paradox made the benefits of red wine into nutritional doctrine. Resveratrol, the main antioxidant in red wine, may even protect against cancer (Jang et al. 1997), although it can also promote atherosclerosis (Wilson et al. 1996).

As is the case with the green tea literature, there is also disagreement on the wine story. Some reports mention increased antioxidant activity in blood serum after red wine consumption (Maxwell et al. 1994), while others suggest it is just the alcohol, independent of the type of beverage, that does the trick (Klatsky et al. 1997). So, the paradox remains. Surely if antioxidants protect the Chinese from lung cancer and the French from heart attacks, we would also expect the Chinese to have fewer heart attacks, and the French to have low lung cancer rates. And shouldn’t both the Chinese and the French live longer than the rest of us?

Reading the Numbers in the Tea Leaves

Experts in tea, wine, and the Mediterranean diet often mention higher life expectancies and frequently make claims of exceptional longevities. These numbers can be measured and are available in several places. The United Nations publishes a vast amount of information on many aspects of human life. The forty-eighth issue of the United Nations Demographic Yearbook (1996) concentrated on mortality statistics.

Unfortunately, the life expectancy statistics are not very helpful. The Yearbooks table 4 gives us male and female life expectancy at birth. When we follow the example of some actuaries and average the male and female numbers to get a less complex picture of unisex data, we see that Mediterranean Greece and France don’t particularly stand out from other industrialized countries. The tea-drinking Japanese are indeed at the top but the tea- drinking Chinese rank last.

Table 1. Unisex life expectancy at birth.

Of course, life expectancy at birth is readily confounded by infant mortality. However, if green tea and red wine are healthy, drinkers should live longer than non-drinkers. The Yearbook’s table 7 contains the numbers of total populations and of the over-65 cohorts, by country. Converting these large, unwieldy numbers into percentages allows for a quick comparison of a few selected countries’ cohorts older than age 65 (table 2, 1990s data). Although population fractions of older people can be confounded by birth rates, table 2 does show a trend, and it doesn’t point the same way as the data on life expectancy.

Japan and France, with high life expectancies, rank below average in the over-65 age group, and Mediterranean Greece ranks below non- Mediterranean Sweden. In Canada and the U.S. the over-65 cohort is much lower. Maybe we eat too much, or perhaps we drive too fast. The Chinese are again at the bottom.

Since we are dealing, presumably, with long-term life styles, it matters little that the Yearbook’s data are from the early 1990s. We find 2003 updates of these figures at the Population Reference Bureau (www.prb.org). And behold, despite worldwide pollution and poor eating habits, in little more than a decade nearly all life expectancies increased by a few years, and the over 65 cohort has grown in all countries. An anomaly in the more recent figures is a jump in the over-65 group in Japan and in Greece to 19 percent of their populations, which bumps Sweden from its top ranking. Whether these are true, one-decade improvements, or just anomalies in data collecting or reporting is unclear.

Table 2. The over-65 cohort as a percentage of total population.

Whatever the benefits of red wine and green tea, so far we see no convincing numbers that a longer life is one of them. However, there are further useful numbers. The Yearbook also shows rates of death by cause in its table 29. China is missing from this table, but there is another source of information for that country. Of course, rate of death due to a given disease is not the same as the incidence, the actual frequency of occurrence, of that disease. Relevant to the green tea issue, the mortality rate due to lung cancer in Japan, at 34.8 per 100,000, is higher than in Israel and Sweden, and marginally lower than in Finland and Norway.

A two-part report sheds light on the Chinese lung cancer issue. In industrialized countries, cigarette smoking in males increased strongly during the early twentieth century, stabilizing by the 1950s. Deaths directly attributable to tobacco began to rise well after mid-century, and reached a plateau in the 1990s. Thus, a delay of several decades separates an increase in smoking from the increase in smoking-related deaths. Early low smoking rates among Chinese males started to increase well after 1952, and only reached today’s high level by 1996. Applying a similar delay, smoking- related deaths in China will reach significantly higher levels only around 2030. Chinese male mortality directly attributable to smoking, about 12 percent in 1990, is expected to rise to 33 percent by 2030 (Liu et al. 1998). Clearly, the idea that China and Japan have the lowest lung cancer rates in the industrial world because of their tea drinking habits is at odds with these readily available health statistics.

In the Yearbook’s table 29 on mortality rates, causes of death are identified by several dozen internationally agreed-upon codes, like AM29 for “acute myocardial infarction,” and AM30 for “other ischemic heart diseases.” An analysis of these numbers shows that, indeed, mortality rates due to heart dis ease in France and Spain are the lowest in the Western world, and lower still in Japan. Greece ranks above nonMediterranean Belgium, but well below the Northern European countries. The Mediterranean and Japanese hearts seem okay, but their arteries are not. That same table 29 in the Yearbook shows that both France and Greece ra\nk among the highest in mortality rates due to circulatory disease.

And in the end, a comparison of all-cause mortality rates makes much of the red wine hype disappear among the many other, different causes from which people die. Curiously, France also has the third highest mortality rate due to liver disease, after Germany and Spain. Alcohol is a liver poison, and more than three drinks daily significantly increases cancer risks. Perhaps alcohol with every meal, be it French wine or German beer, is not such a good idea after all.

Other Explanations

Some data seem to support claims that the Japanese have the highest average life span among industrialized countries, although these claims seem to be based on a comparison of life expectancies (Kobayashi 1992). Also, the Mediterranean countries do have lower total mortality rates than the Scandinavians, though these rates are lower still in Japan, Canada, and Australia. However, there are several other interesting observations that offer more plausible explanations than the tea and wine stories.

British researchers proposed a simple explanation for the French Paradox. Consumption of animal fat, a major dietary cause of heart disease, increased substantially in France between 1965 and 1988. Their study also shows a considerable time lag between long-term fat consumption and the onset of atherosclerosis. They explain the current low rate of heart disease in France by a simple time-lag phenomenon, and predict that this rate will rise in the coming decade (Law and Wald 1999). A similar increase in the consumption of animal fat took place in several other Mediterranean countries (Serra-Majem et al. 1995, Matalas et al. 2001). The story is not unlike that of the cigarette smoking Chinese. Clearly, the Mediterranean diet is changing. Again, proof is still some years away.

Spanish researchers also studied diet and heart disease in their country. They came up, surprise, with the Spanish Paradox (Serra- Majem et al. 1995). That report did not generate the same fuss as the French Paradox, maybe because the Spaniards lacked the glamour of the red wine. Their “paradoxical” results do show a decrease in heart disease mortality from the mid 1970s onward. However, during the two relevant decades, the Spanish dramatically increased their consumption of meat, fat, and dairy products. They also decreased their consumption of super-healthy olive oil and replaced it with cheaper seed oils. Also, the Spanish researchers could not use red wine to explain their paradox, because between 1975 and 1995 Spanish wine consumption decreased by nearly 50 percent. These observations contrast markedly with current popular view of the Mediterranean diet. Not surprisingly, that report concludes with the suggestion that diet, although important, is probably not as important as other factors operating in Spain, and elsewhere, such as improved medical resources, an aggressive antismoking campaign, and the increased use of aspirin as a preventive blood thinner.

Then there is the story about a gene on human chromosome 19, which codes for a protein called apolipoprotein E. When this apolipoprotein binds with cholesterol and fatty acids, it forms the high and low density lipoproteins (HDL and LDL) that control the transport of fats in our blood. Inherited variations in this gene lead to different forms of apolipoprotein E. A variant called E3 is better at handling fat transport than another variant called E4. If your parents gave you the E3 variant, you can handle dietary fat better, and your risk of cardiovascular disease is lower, than if you were born with the gene for E4. Very few diet writers mention this important influence of genetics (Matalas et al. 2001).

The gradient of the frequency distribution of these genetic variants across Europe almost look like the isobars on a weather map, with E3 more prevalent in southern Europe, around the Mediterranean, and E4 much more common in the North (Lucotte et al. 1997). When it comes to cardiovascular disease and fat metabolism, South Europeans have a genetic advantage. Yes, heart disease is less common in the Mediterranean area. Whether it is their diet or their genes, we don’t know. Perhaps the Mediterraneans are just a few decades behind with destroying their healthy eating habits.

A similar effect, hidden in the genetic past of human evolution, may explain Japanese longevity. In a Japanese study we find that a mutation in mitochondrial DNA, which may be linked to longevity, is relatively rare in the global population, but occurs in almost half the population of Japan. Japanese longevity, if it is real, may have more to do with a genetic quirk than with diet (Tanakaetal. 1998).

So, while green tea is still hidden in the fog of uncertainty, it may be a good idea to hang on to Happy Hour. There are definite indications that a few drinks a day of any alcoholic beverage can reduce the risk of heart disease, although evidence that red wine is best remains elusive (German and Walzem 2000). And the Mediterranean diet, stripped of the hoopla of the French Paradox, does have distinct health benefits, both in terms of survival after cancer (De Lorgeril et al. 1998), and after a first heart attack (Matalas et al. 2001).

Clearly, there is little evidence for labeling green tea as an anti-cancer beverage. And what happens to our hearts may have more to do with our genes than with red wine. Still, maintaining good drinking habits seems a good idea.

Like many other plant extracts, green tea inhibits growth of cancer cells in the lab and in some rodents, but studies on humans are quiete inconclusive.

References

Bushman, J. L. 1998. Green tea and cancer in humans: A review of the literature. Nutrition and Cancer 31(3):151-159.

De Lorgeril, M., et al. 1998. Mediterranean dietary pattern in a randomized trial: prolonged survival and possible reduced cancer rate. Archives of Internal Medicine 158(11):1181-7.

German, J. B., and R. L. Walzem. 2000. The health benefits of wine. Annual Reviews of Nutrition 20:561-93.

Jang, M., et al. 1997. Cancer chemopreventive activity of resveratrol, a natural product derived from grapes. Science 275:218- 220.

Klatsky, A. L., et al. 1997. Red wine, white wine, liquor, beer, and risk for coronary artery disease hospitalization. American Journal of Cardiology 80(4):416-20.

Kobayashi, S. 1992. A scientific basis for the longevity of Japanese in relation to diet and nutrition. Nutrition Reviews 50(12):353-354.

Law, M., and N. WaId. 1999. Why heart disease mortality is low in France: the time lag explanation. British Medical Journal 318:471- 80.

Liu, B. Q., et al. 1998. Emerging tobacco hazards in China: Part 1. Retrospective proportional mortality study on one million deaths. British Medical Journal 317:1411-22. Part 2. Early mortality results from a prospective study. Ibid.: 1423-4.

Lucotte, G., et al. 1997. Pattern of gradient of apolipoprotein E allele 4 frequencies in Western Europe. Human Biology 69(2):253- 262.

Matalas, A. L., et al. Eds. 2001. The Mediterranean diet: constituents and health promotion, Boca Raton: CRC Press.

Maxwell, S., et al. 1994. Red wine and antioxidant activity in serum. Lancet 344:193-4.

Montignac, M., 1999. Eat Yourself Slim. Baltimore: Erica House, p.120.

Renaud, S. and M. de Lorgeril. 1992. Wine, alcohol, platelets, and the French paradox for coronary heart disease. The Lancet 339:1523-6.

Serra-Majem, L., et al. 1995. How could changes in diet explain changes in coronary heart disease mortality in Spain? The Spanish Paradox. American Journal of Clinical Nutrition 61 (SuppL): 1351S- 9S.

Tanaka, M., et al. 1998. Mitochondrial genotype associated with longevity. Lancet 351 (9097):185-6.

United Nations Demographic Yearbook, 48th Issue, 1996. Special issue on mortality statistics.

Wilson, T., et al.1996. Resveratrol promotes atherosclerosis in hypercholesterolemic rabbits. Life Sciences 59(1): 15-21.

William H. Baarschers is a professor emeritus of chemistry at Lakehead University in Thunder Bay, Ontario. His research interests have included the chemistry of medicinal plants, synthetic chemistry, environmental science, and industrial toxicology. He is currently an advisor to the university’s Resource Centre for Occupational Health and Safety. He is the author of Eco-Facts and Eco-Fiction: Understanding the Environmental Debate (Routledge, 1996).

Copyright The Committee for the Scientific Investigation of Claims of the Paranormal (SCICOP) Sep/Oct 2005

Summary

This article outlines the causes, signs and symptoms of systemic inflammatory response syndrome (SIRS), sepsis, severe sepsis and septic shock, the implications and available treatments. The article also highlights a campaign to reduce the incidence of sepsis and reflects on efforts to reduce healthcare-associated infections.

Keywords

Bacterial infections; Patient assessment; Sepsis; Shock

These keywords are based on the subject headings from the British Nursing Index. This article has been subject to double-blind review. For related articles and author guidelines visit our online archive at www.nursing-standard.co.uk and search using the keywords.

Aim and intended learning outcomes

The aim of this article is to raise awareness of sepsis, so that nurses will have a greater understanding of this condition and feel more confident in the identification and treatment of patients with sepsis. After reading this article you should be able to:

* Describe the standard definitions of systemic inflammatory response syndrome (SIRS), sepsis, severe sepsis and septic shock.

* Identify patients with SIRS, sepsis, severe sepsis and septic shock.

* Understand the main physiological changes that occur in sepsis and their implications.

* Describe the initial treatment for a patient with severe sepsis.

* Discuss the current evidence-based therapies for managing patients with severe sepsis and septic shock.

* Outline the main aims of the Surviving Sepsis Campaign.

* Reflect on how current efforts to reduce healthcare-associated infections may help to reduce the incidence of sepsis.

* Identify strategies to raise awareness about sepsis in your clinical area.

Introduction

Sepsis affects 18 million people worldwide each year (Slade et al 2003). Nurses in all areas of practice, from the community to acute hospitals, will care for septic patients during their professional careers. However, although it is a common problem, many nurses receive little training in how to identify patients with severe sepsis correctly or about how important early and aggressive treatment is to help prevent the condition deteriorating. There also appears to be confusion over the definition of sepsis, with a variety of terms such as septic, bacteraemia, sepsis, septicaemia and septic shock being used interchangeably.

Over the last few decades there has not been a dramatic improvement in survival rates for sepsis (Friedman et al 1998). In recognition of the seriousness of the problem, an international campaign, called the Surviving Sepsis Campaign, which is run mainly by the Institute of Health Improvement (www.ihi.org/IHI/Topics/ CriticalCare/Sepsis) is now under way to raise awareness of sepsis around the world and promote evidence-based care. It is hoped that by so doing, the death rate from sepsis can be reduced significantly.

Defining sepsis

Sepsis is a word that nurses use frequently. However, in the past there has been a general lack of consensus about the definition of sepsis. In response to this, in 1991, experts from around the world produced clear and concise definitions for sepsis, severe sepsis and septic shock, and introduced the term systemic inflammatory response syndrome (SIRS) (Bone et al 1992).

Definitions (Bone et al 1992, Levy et al 2001, Dellinger et al 2004):

Systemic inflammatory response syndrome (SIRS) This is the body’s response to a variety of insults and is manifested by two or more of the following conditions:

* High or low temperature >38C or

* Heart rate >90 beats per minute.

* Respiratory rate > 20 breaths per minute or PaCO^sub 2^ (partial pressure of arterial carbon dioxide)

* High or low white blood cell count > 12,000 or

Although the SIRS response is produced by an infection in sepsis, SIRS can also be caused by any major insult to the body, such as burns, acute pancreatitis, myocardial infarction or trauma. Nurses and doctors should consider whether SIRS is caused by an infection or some other insult.

Sepsis This is a known or suspected infection, accompanied by evidence of two or more of the SIRS criteria mentioned above.

Severe sepsis This is sepsis (a known or suspected infection with two or more of the SIRS criteria), associated with organ dysfunction, hypotension or poor perfusion. All organs, including the cardiovascular system, lungs, liver, kidneys and brain can be affected. Signs of organ dysfunction are:

* Hypotension – defined as a systolic blood pressure

* Altered mental state – it is important to involve the patient’s family to assess an alteration.

* Hyperglycaemia in the absence of diabetes.

* Hypoxaemia – oxygen saturation (SpO^sub 2^)

* Acute oliguria – urine output

* Coagulopathy-INR (International Normalised Ratio) >1.5, APTT (activated partial thromboplastin time) >60 seconds or platelets

* Serum lactate >2mmol/L (Box 1).

Organ dysfunction can also affect the liver-evidenced by abnormal liver function tests (LFTs) and the gastrointestinal tract – evidenced by bowel stasis (ileus).

Septic shock This is severe sepsis with hypotension (systolic blood pressure below 90mmHg), which does not respond to adequate fluid resuscitation (approximately 1.5-2.0 litres of fluid) (Dellinger et al 2004). Additional signs and symptoms to consider at the bedside when deciding if a patient has sepsis are: a positive fluid balance, an unexplained metabolic acidosis (a blood pH value -2.5 mmol/L and decreased capillary refill, or mottling of the skin (Levy et al 2001).

Capillary refill time is measured by applying pressure to a fingertip, held at heart level for five seconds, and then letting go while counting how long it takes the finger to return to a pink colour. Normally this happens in less than two seconds. Patients with sepsis often have warm peripheries and a normal or brisk capillary refill , of two seconds or less, as a result of vasodilation. However, it is important to note that patients with severe sepsis may also present with cool peripheries and a longer capillary refill time of greater than two seconds. This can result from the reduced pumping force of the left ventricle.

BOX 1

Serum lactate

Despite the agreed sepsis definitions, it appears that some medical staff are not aware that these common definitions exist. Of the 1,058 doctors questioned in Poezeeiafs (2004) study, no more than 17 per cent agreed on any one definition and 83 per cent said it is likely that sepsis is missed frequently. There do not appear to be any published studies that have explored nurses’ knowledge of diagnosing sepsis, but many nurses may not be aware of these common definitions, and may, as a result, fail to recognise that a patient is septic. All health professionals need to know the signs and symptoms to work effectively as a team.

For sepsis to be treated, it should first be recognised using a common agreed definition. This requires nurses to be as familiar with the j signs and symptoms of severe sepsis as might be expected with the signs and symptoms of venous thromboembolism, or angina. Many patients can have sepsis and not be particularly ill. This is uncomplicated sepsis of the kind experienced by people with influenza or a chest infection. Such individuals have a known or suspected infection, and two or more of the SIRS criteria, but do not require hospital treatment (International Sepsis Forum (ISF) 2002).

It has been suggested that some individuals may be genetically more susceptible to developing severe sepsis or septic shock than others (ISF 2002). There is no single cause of sepsis and the clinical presentation can vary from uncomplicated sepsis to septic shock with multiple organ failure and death (ISF 2002).

BOX 2

Bacteria associated with sepsis

Common causes of sepsis

Sepsis can result from an infection in various parts of the body and although a lay understanding of sepsis might include reference to blood poisoning positive blood cultures are not needed to diagnose it. About 90 per cent of the cases of sepsis are caused by bacteria (Box 2), but sepsis can also be caused by viruses or fungi, particularly Candida spp. (Cohen et al 2004).

Infection is a major reason for patients to be admitted to hospital and some patients may develop infections while in hospital (Department of Health (DH) 2003). Infections can be found in any system of the body. The most common sources of infection that can lead to sepsis are:

* Respiratory tract-community-acquired or healthcare-associated (nosocomial) pneumonia.

* Intra-abdominal cavity- infection might result from diverticulitis, appendicitis, a perforated bowel, and ischaemic or necrotic bowel.

* Central nervous system – such as meningitis.

* Genitourinary system – uro-sepsis is an infection which might result from an obstruction in the urinary system, or a catheter- related infection.

* Skin – wound infections, cellulitis or necrotising infections of the skin and soft tissues with rapid destruction of tissue, such as necrotising fasciitis.\* Intravascular catheters – any invasive catheter, for example, central venous catheters or peripheral cannulae.

Patients whose immune system is compromised are at increased risk of developing sepsis. Those at risk include the very young, whose immune systems are not completely developed, and older people, whose immune systems have become weakened as a result of the ageing process. Also at risk are those who have had a transplant, a splenectomy or those who are being treated with radiation or chemotherapy, and patients with diabetes, cancer, human immunodeficiency virus (HIV) or acquired immunodeficiency syndrome (AIDS) (ISF 2002).

The body’s response to sepsis

In understanding the changes that happen to the body in severe sepsis it is helpful to remind ourselves of the changes that occur during the normal immune response. Cells damaged by infection from bacteria, viruses, chemical agents or trauma produce the same non- specific defensive response of inflammation. Regardless of the cause, inflammation has three basic phases: vasodilation and increased permeability of blood vessels; emigration of phagocytes; and tissue repair (Tortora and Grabowski 2000).

Vasodilation brings more blood to the damaged area, and the increased permeability allows phagocytes and antibodies to pass out from the circulation. The clotting cascade is also activated. Clot formation is part of the normal immune response, and may be the body’s attempt to confine any invading organisms to one area of the body (Ahrens and Vollman 2003). This inflammatory response and activation of the clotting system are designed to repair damaged tissues and prevent further damage.

Inflammation is a normal physiological response to a variety of insults, and normally the body restricts the inflammation to the local site of the infection. Severe sepsis, however, produces an exaggerated, excessive, inflammatory response throughout the body. A variety of inflammatory mediators such as histamine, prostaglandins and cytokines, including tumour necrosis factor (TNF), and interleukins, are released into the circulation. These cause widespread vasodilation. Blood vessels widely dilate causing the blood pressure to plummet (Figure 1). The capillaries become more permeable allowing fluid to leak out of the circulation. This produces hypovolaemia which can lower the blood pressure further. The coagulation system also becomes activated and small blood clots (microthrombi) form in the small blood vessels (Figure 2). These thrombi interfere with blood flow to the tissues and organs and, in combination with hypotension and hypovolaemia, can lead to organ failure.

FIGURE 1

Vasodilation

FIGURE 2

Formation of microthrombi in the small blood vessels

Normally the body will attempt to break down any blood clots by fibrinolysis and will also release anti-inflammatory mediators to counterbalance the inflammatory mediators (Balk et al 2004). However, in patients with severe sepsis fibrinolysis is inhibited by the release of plasminogen-activator inhibitor (PAI), which prevents the breakdown of microthrombi. The inflammatory and procoagulation response is very persistent, such that the body is unable to restore homeostasis.

The endothelium, the innermost layer of the blood vessels, also plays an important role in the inflammatory response. In sepsis the endothelium becomes activated and then damaged. The endothelium releases nitric oxide (NO) which also causes small blood vessels to dilate (Balk et al 2004).

Sepsis

The mortality rate from severe sepsis is high at 28-50 per cent (Angus et al 2001), and there are about 21,000 cases each year of severe sepsis in England and Wales (National Institute for Clinical Excellence (NICE) 2004). Sepsis is very common and, because it is often under recognised, the incidence may be even higher than presently recorded. A patient who dies of sepsis as a result of pneumonia, may have his or her cause of death recorded as pneumonia rather than multiple organ failure as a result of severe sepsis or septic shock (Ahrens and Vollman 2003).

The management of patients with severe sepsis is expensive for the NHS. These patients often require prolonged stays in an intensive care unit (ICU), and multiple supportive therapies, such as mechanical ventilation, renal support (haemofiltration), and respiratory therapy rotational beds. They account for 46 per cent of all ICU bed days, and the average cost per day of ICU in the UK in 2002 was 1,232 (NICE 2004). This cost burden appears set to rise as the incidence of sepsis in the future is estimated to grow by 1.5 per cent per year (Angus et al 2001). This is because of the ageing population, new types of surgery, and medical technology such as central venous catheters, mechanical ventilators and haemofiltration, all of which put patients at risk of sepsis. Antibiotic resistance may also be a contributing factor (Angus et al 2001).

Recovery from critical illness can be a long and slow process. Critical care patients with severe sepsis are among the most sick and are, therefore, most likely to experience the longest periods of recovery. Montuclard et al (2000) found that in a group of older ICU survivors one year after discharge, 26 per cent had difficulty transferring from chairs or beds, 23 per cent had difficulty bathing and 15 per cent had difficulty toileting. Any efforts to diagnose severe sepsis as early as possible and deliver prompt and aggressive treatment may mean that patients are less sick when they arrive in ICU with fewer failing organs, possibly resulting in a shorter stay and a less protracted recovery.

The Surviving Sepsis Campaign

The high death rate from severe sepsis has prompted a joint response from the many intensive care societies around the world. In October 2002, the Surviving Sepsis Campaign was officially launched by the European Society of Intensive Care Medicine, the Society of Critical Care Medicine and the International Sepsis Forum. This is an international effort to bring about rapid improvement in the standard of care of patients with severe sepsis. The main aims of the campaign are to (Dellinger et al 2004):

* Increase awareness of sepsis, severe sepsis and septic shock among healthcare staff and the general public.

* Develop evidence-based guidelines for the management of severe sepsis.

* Ensure that the guidelines are put into practice to create a global standard of care for patients with sepsis.

* Reduce the mortality from sepsis worldwide by 25 per cent in the five years following the publication of evidence-based guidelines in 2004.

It is essential that nurses are aware of the evidence-based guidelines as their role is crucial to the success of the campaign. Nurses are in an ideal position to identify the first signs of a patient developing sepsis, and the sooner treatment begins the less likely the condition is to spread and result in organ dysfunction or failure (Ahrens and Juggle 2004).

Treating severe sepsis

When treating trauma patients the first hour following injury is known as the ‘golden hour’ because the treatment given or not given during that time can have a significant impact on their survival, and how ill patients ultimately become in the hours and days that follow (American College of Surgeons (ACS) 1997). Prompt treatment with oxygen and intravenous fluids prevents secondary injury to organs as a result of hypoxia and hypotension, thus reducing mortality and morbidity. Patients with severe sepsis share an early window of opportunity in which aggressive treatment can influence survival and the severity of illness (Ahrens and Tuggle 2004).

To be able to treat patients in the ‘golden hour’ following the onset of severe sepsis, we must first be able to recognise it confidently. Patients with severe sepsis or septic shock will need to be cared for on high-dependency units (HDUs) or ICUs. Studies have shown that patients admitted to ICU from the wards are often not referred early enough and sometimes receive suboptimal care on the ward which can increase their mortality (McQuillan et al 1998). Vincent et al (2002) suggest that some patients with sepsis are recognised late and are not treated appropriately before transfer to ICU.

Any patient on a general ward or in a primary care setting whose condition is causing concern or who triggers an Early Warning Score, a method of identifying patients at risk of critical illness developed by critical care outreach teams (McArthur-Rose 2001), should be assessed initially using the airway, breathing, circulation, disability (A, B, C, D) approach (University of Portsmouth 2003). This systematic approach ensures that life- threatening problems are assessed and managed in order of importance. It is based on the rationale that the patient’s airway should always be assessed and managed before anything else because an obstructed airway will kill the patient before a problem with breathing (B) or circulation (C). After the airway has been managed the patient’s breathing should be assessed before circulation.

In March 2004 the Surviving Sepsis Campaign produced comprehensive guidelines on the management of patients with severe sepsis (Dellinger et al 2004).

Initial treatment within one hour of diagnosis

* Perform baseline observation of vital signs: respiration rate, oxygen saturation (SpO^sub 2^), capillary refill time, heart rate, and blood pressure. Consider the patient’s level of consciousness – is he or she alert or drowsy? Level of consciousness is represented by the D of the ABCD approach and refers to disability of the central nervous system.

* Give supplemental oxygen therapy, via a face mask, to achieve SpO^sub 2^ > 95 per cent.

* Obtain blood specimens: lactate, full blood count, urea and electrolytes, glucose, liver function tests, clotting screen and blood cultures (Box 3).

* Administer intravenous broad spectrum antibiotics. In severe sepsis antibiotics should be given within \one hour of diagnosis (Dellinger et al 2004). Giving prompt antibiotic therapy may reduce mortality by 10-15 per cent, compared with patients in whom antibiotic therapy is delayed (Wheeler and Bernard 1999).

* Any septic patient who has a lactate level above 4mmol/L should be considered to have severe sepsis even if his or her blood pressure is within his or her normal range.

* If systolic blood pressure is 40mmHg lower than the patient’s normal blood pressure, administer intravenous fluid challenges. A fluid challenge is usually 500ml given over five to ten minutes (University of Portsmouth 2003).

* If the patient remains hypotensive consider insertion of a central venous catheter, and the continuation of intravenous fluid challenges to achieve a central venous pressure (CW) of 8-12mmHg. Patients who do not respond to fluid challenges and remain hypotensive after having 1.5-2.0 litres may require vasoconstricting drugs, such as noradrenaline (norepinephrine).

BOX 3

Blood cultures

* Insert a urinary catheter with an hour urometer that allows the hourly urine volume to be measured – and obtain a urine specimen.

Ongoing management of severe sepsis

* Observe the patient – perform half-hourly observations of vital signs and hourly measurement of urinary output.

* Source control – every patient with severe sepsis should be examined to establish a source or a focus of infection that is causing the sepsis. If a source is identified prompt action should be taken to control or eliminate it (Dellinger et al 2004). Surgery for obstructed bowel or ischaemic and necrotic bowel, debridement of infected or necrotic tissue, drainage of an abscess and removal of an infected intravenous catheter are all examples of source control. Source control should be carried out after initial resuscitation, as it can prevent further organ damage and improve the patient’s chances of survival.

* Consider referral and transfer of the patient to a HDU or ICU.

New therapies

In the past five years new therapies have emerged that have been shown to increase the chances of survival from severe sepsis significantly.

Early goal-directed therapy Early goal-directed therapy is a form of early and aggressive resuscitation for patients with severe sepsis based on the findings of a research study carried out in the US by Rivers et al (2001). The study showed that if patients with severe sepsis admitted to the accident and emergency department were given aggressive resuscitation, including measurement of central venous oxygen saturations in the first six hours of diagnosis, their chances of survival were increased by 16 percent (Rivers et al 2001).

The early goal-directed therapy protocol should be used in patients who have severe sepsis and remain hypotensive (systolic blood pressure 65mmHg. If this cannot be achieved after receiving up to two litres of fluid a noradrenaline (norepinephrine) infusion is commenced.

A special central venous catheter is inserted (Figure 3) that can measure the oxygen saturations of venous blood, in the vena cava where the tip of the catheter sits (Figure 4). The normal value for central venous oxygen saturations is approximately 75 per cent. Central venous oxygen saturations represent the balance between the oxygen delivered to the tissues and the oxygen consumed by the tissues. The normal saturation of venous blood returning to the right side of the heart is approximately 75 per cent because the tissues usually consume, or extract, approximately 25 per cent of the oxygen delivered. Some patients with severe sepsis will have central venous oxygen saturations much less than 75 per cent, indicating that the tissues are being starved of oxygen and to compensate are extracting more oxygen than normal (Ahrens and Tuggle 2004).

Rivers et al (2001) aimed to keep the central venous saturations >70 per cent to ensure the tissues and organs received enough oxygen. If a patient’s saturations were

Although it would not be possible to carry out early goal- directed therapy fully in a ward area, it is possible to identify promptly patients with severe sepsis who would be eligible for early goal-directed therapy, and give antibiotics and fluid boluses, while patient transfer is organised. Nurses in the ward area can help to ensure that antibiotics are commenced without delay, blood tests and blood cultures are obtained and that the patient’s vital signs are monitored carefully observing for any signs of deterioration. Ward nurses also have a key role in informing the critical care outreach team of these patients. Patients eligible for early goal-directed therapy are those whose systolic blood pressure remains 4mmol/L (Rivers et al 2001).

Activated protein C

Activated protein C is a naturally occurring protein made by the body and is both an anticoagulant and an anti-inflammatory. It promotes fibrinolysis and inhibits thrombosis as well as reducing inflammation by blocking the release of cytokines. It would be the perfect remedy to counteract the multiple small thrombi and widespread inflammation that characterise severe sepsis, but the body’s ability to convert protein C to activated protein C in severe sepsis is impaired because sepsis diminishes the ability to produce thrombin which is necessary for this process (Yan et al 2001).

A randomised controlled trial, known as the Prowess trial (Bernards et al 2001), compared the use of activated protein C with a placebo treatment in patients with severe sepsis/septic shock. The results showed that patients treated with activated protein C were more likely to survive. The death rate in the activated protein C group was 6 per cent lower than in the group who did not receive it.

Activated protein C is known as drotrecogin alfa (activated) and has been evaluated by NICE (2004). It is now recommended ‘for use in adult patients who have severe sepsis that has resulted in multiple organ failure (that is two or more major organs have failed) and who are being provided with optimal ICU support’ (NICE 2004).

Activated protein C may potentially increase the risk of bleeding, and may be contraindicated in certain patients. Activated protein C is a relatively expensive treatment. The cost for a 70kg patient is 4,905 (NICE 2004). However, although expensive, treatment with activated protein C may lead to a reduced length of stay in ICU. The average cost per day to keep a patient in ICU was estimated at 1,232 in 2002 (NICE 2004).

FIGURE 3

Central venous catheter for monitoring central venous oxygen saturations

FIGURE 4

Measuring venous oxygen saturations in early goal-directed therapy

Reducing the incidence of sepsis

Some patients develop severe sepsis from infections that they acquire while in hospital. One in ten NHS hospital patients are affected by healthcare-associated infections (HCAIs) each year (DH 2003) and the National Audit Office (2000) estimates the cost of these at 1 billion per year. The most common of these infections are urinary infections as a result of indwelling urinary catheters and pneumonia.

The DH’s (2003) document Winning Ways states that evidence-based countermeasures to reduce HCAIs are not being implemented effectively in the majority of hospitals. Nurses must make continued efforts to play an active part in reducing the number of HCAIs as this can potentially lead to fewer patients developing sepsis in hospital.

Ahrens and Tuggle (2004) suggest that it may also be beneficial to raise the public’s awareness of the Surviving Sepsis Campaign and the warning signs of developing sepsis, in the same way that the public is made aware of the signs of a heart attack and urged to seek prompt medical care. This may help to achieve the main aim of the campaign which is to reduce mortality.

Conclusion

Sepsis is a common condition and can be fatal. A good knowledge of the signs and symptoms of sepsis, SIRS, severe sepsis and septic shock is the key to prompt recognition. Every patient suspected of having severe sepsis should have blood taken for a serum lactate level. In patients with severe sepsis, early aggressive treatment and adherence to evidence-based guidelines can help to save lives. In addition, efforts to reduce HCAIs can aid in the reduction of the incidence of severe sepsis

NS306 Robson W, Newell J (2005) Assessing, treating and managing patients with sepsis. Nursing Standard. 19, 50, 56-64. Date of acceptance: June 24 2005.

Time out 1

Reflect on your understanding of systemic inflammatory response syndrome (SIRS), sepsis, severe sepsis, and septic shock. If you had to explain these terms to a junior colleague what would you say? Think about the patients you have cared for with sepsis, what signs and symptoms did they have and what treatment did they receive?

Time out 2

Reflect on the scenarios below and consider if these patients have sepsis, severe sepsis, or septic shock and list the reasons for your answer:

1. Mary is 51 years old and has been treated by the GP for a chest infection for the past week. Today she has deteriorated and returned to the GP, who immediately called an ambulance. Her signs and symptoms on arrival to the A&E department are:

* Respiratory rate: 28

* Oxygen saturation: 92% on 60% oxygen

* Pulse: 124 beats per minute

* Blood pressure: 140/63mmHg

* Temperature: 35.9 C

* White cell count: 9,000.

2. Alan is a 71-year-old man who had a laparotomy seven days ago. The ward nurse looking after him h\as contacted the critical care outreach team as Alan is scoring 5 on the hospital Early Warning Score. His signs and symptoms are:

* Respiratory rate: 26

* Pulse: 105 beats per minute

* Blood pressure: 89/56mmHg

* Urine output: 25ml for the past two hours consecutively

* Drowsy but responds to voice

* Temperature: 38.4C

* White cell count: 18,000

* The full blood count shows his platelets are 76.

(Answers on page 64)

Time out 3

Think about how you might begin explaining to a relative that his or her loved one has developed severe sepsis resulting in multi- organ failure and has been transferred to the intensive care unit. Consider the lay understanding of sepsis and the questions that relatives might ask.

Time out 4

Visit the following websites:

www.ihi.org/IHI/Topics/CriticalCare/Sepsis

www.sepsisforum.org

www.survivingsepsis.org

(Last accessed: August 10 2005.)

You may find some useful resources to download for your clinical area.

Time out 5

Veronica had a laparotomy for Crohn’s disease two days ago.

Today she has severe abdominal pain. Her observations are:

* Respiratory rate: 32

* Pulse: 137 beats per minute

* Blood pressure: 90/46mmHg

* Urine output: 20-22ml/hr for two hours

* Temperature: 38.6C

Does this patient have severe sepsis? What immediate treatment should be given? The doctor on the ward is a newly qualified pre- registration house officer and asks your advice about giving a fluid challenge, how much and how quickly? What blood pressure and urine output should you aim to achieve for this patient?

Some hospitals have introduced patient group directions to enable nurses to administer fluid boluses in certain situations, such as hypotension and low urine output. Reflect on the risks and benefits of this, and how it might help in the treatment of septic patients on the wards or in primary care?

Time out 6

Make a list of the actions you could be undertaking to raise awareness of sepsis, and prevent it occurring in your area of practice. Think about spending a day in ICU, HDD or A&E to learn more about patients with severe sepsis. Examine their notes and reflect on how they presented, how a diagnosis was reached, which organ systems were affected and what treatment they received.

Time out 7

Now that you have finished the article you might like to write a practice profile. Guidelines are on page 68.

Answers to Time out activity 2

1. Mary has sepsis. She has an infection with three of the systemic inflammatory response syndrome (SIRS) criteria. There is also evidence of respiratory dysfunction as she requires 60% oxygen and her saturations remain low.

2. Alan has severe sepsis, a suspected infection possibly from his wound or chest. He fulfils the SIRS criteria as his vital signs are: temperature 38C, pulse over 90, with a respiratory rate above 20. There are signs of organ dysfunction, a low blood pressure indicating cardiovascular problems, a low urine output indicating renal impairment and low platelets indicating coagulation dysfunction.

References

Ahrens T, Tuggle D (2004) Surviving severe sepsis: early recognition and treatment. Critical Care Nurse. 24, 5, Suppl, 2-13.

Ahrens T, Vollman K (2003) Severe sepsis management: are we doing enough? Critical Core Nurse. 23, 5, Suppl, 2-15.

American College of Surgeons (1997) Advanced Trauma Life Support Student Manual. American College of Surgeons, Chicago IL.

Angus DC, Linde-Zwirbie WT, Lidicker J et al (2001) Epidemiology of severe sepsis in the United States: analysis of incidence, outcome and associated costs of care. Critical Care Medicine. 29, 7, 1303-1310.

Balk RA, Ely EW, Goyette RE (2004) Sepsis Handbook. Thomson Advanced Therapeutics Communications'”, Vanderbilt University School of Medicine Nashville, Tennessee TN.

Bernard GR, Vincent JL, Laterre PF et al (2001) Efficacy and safety of recombinant activated protein C for severe sepsis. New England Journal of Medicine. 344, 10, 699-709.

Bone RC, Balk RA, Cerra FB et al (1992) American College of Chest Physicians/Society of Critical Care Medicine Consensus Conference: definitions for sepsis and organ failure and guidelines for the use of innovative therapies in sepsis. Chest. 101, 6, 1644-1655.

Cohen J, Brun-Buisson C, Torres A, Jorgensen J (2004) Diagnosis of infection in sepsis: an evidence-based review. Critical Care Medicine. 32, 11, S466-S494.

Dellinger RP, Carlet JM, Masur H et al (2004) Surviving Sepsis Campaign guidelines for management of severe sepsis and septic shock. Critical Care Medicine. 32, 3, 858-873.

Department of Health (2003) Winning Ways: Working Together to Reduce Healthcare Associated Infection in England. The Stationery Office, London.

Edwards S (2001) Shock: types, classifications and explorations of their physiological effects. Emergency Nurse. 9, 2, 29-38.

Friedman G, Silva E, Vincent JL (1998) Has the mortality of septic shock changed with time? Critical Care Medicine. 26, 12, 2078- 2086.

International Sepsis Forum (2002) Promoting a Better Understanding of Sepsis. www.sepsisforum.org (Last accessed: August 11 2005.)

Levy MM, Fink MP, Marshall JC et al (2001) SCCM/ ESICM/ACCP/ATS/ SIS International Sepsis Definitions Conference. Critical Care Medicine. 31, 4, 1250-1256.

McArthur-Rose F (2001) Critical care outreach services and early warning scoring systems: a review of the literature. Journal of Advanced Nursing. 36, 5, 696-704.

McQuillan P, Pilkington S, Allan A et al (1998) Confidential inquiry into quality of care before admission to intensive care. British Medical Journal. 316, 7148, 1853-1858.

Montuclard L, Garrouste-Orgeas M, Timsit JF, Misset B, DeJonghe B, Carlet J (2000) Outcome, functional autonomy, and quality of life of elderly patients with a long-term intensive care unit stay. Critical Care Medicine. 28, 10, 3389-3395.

National Audit Office (2000) The Management and Control of Hospital Acquired Infection in Acute Trusts in England. The Stationery Office, London.

National Institute for Clinical Excellence (2004) Drotrecogin alfa (activated) for severe sepsis. Technology Appraisal 84. NICE, London.

Poeze M, Ramsay G, Gerlach H, Rubulotta F, Levy M (2004) An international sepsis survey: a study of doctors’ knowledge and perception about sepsis. Critical Care. 8, 6, R409-R413.

Rivers E, Nguyen B, Havstad S et al (2001) Early goal-directed therapy in the treatment of severe sepsis and septic shock. New England Journal of Medicine. 345, 19, 1368-1377

Slade E, Tamber PS, Vincent JL (2003) The Surviving Sepsis Campaign: raising awareness to reduce mortality. Critical Care. 7, 1, 1-2.

Tortora GJ, Grabowski SR (2000) Principles of Anatomy and Physiology. Ninth edition. John Wiley & Sons, New York NY.

University of Portsmouth (2003) Acute Life-Threatening Events Recognition and Treatment (ALERT(TM)) Course Manual. Second edition. University of Portsmouth, Portsmouth.

Vincent JL, Abraham E, Annane D, Bernard G, Rivers E, Van den Berghe G (2002) Reducing mortality in sepsis: new directions. Critical Care. 6, Suppl 3, S1-S18.

Wheeler AP, Bernard GR (1999) Treating patients with severe sepsis. New England Journal of Medicine. 340, 3, 207-214.

Van SB, Helterbrand JD, Hartman DL, Wright TJ, Bernard GR (2001) Low levels of protein C are associated with poor outcome in severe sepsis. Chest. 120, 3, 915-922.

Authors

Wayne Robson is nurse consultant critical care, and Julian Newell is senior charge nurse, accident and emergency department, Chesterfield Royal Hospital NHS Foundation Trust, Derbyshire. Email: [email protected]

Copyright RCN Publishing Company Ltd. Aug 24-Aug 30, 2005

Teri Jeansonne knew she was better when she could turn and yell at her kids in the car.

A victim of the autoimmune disease scleroderma, the 42-year-old mother of three could feel her body turning to stone before she signed up for an experimental treatment with a potent cancer drug.

“I would get up to take the kids to school in the morning and go home and go back to bed. I could barely move and I hurt from my chin to my toes. I was using morphine patches and taking 31 pills a day and nothing helped.”

When Jeansonne’s insurance company wouldn’t pay for her to go to Johns Hopkins for an experimental chemotherapeutic treatment, her doctors at Ochsner Clinic agreed to treat her here.

“We had tried everything else and Teri was still getting worse. She was going to die in six to 12 months,” rheumatologist Stephen Lindsey said. Ochsner oncologist Jay Brooks was called in, and Dr. Fredrick Wigley, director of Johns Hopkins Scleroderma Center, was consulted to place Jeansonne on an intensive dose of Cytoxan.

Scleroderma, which means “hard skin,” is a spectrum disorder with a wide range of symptoms and outcomes, Lindsey said. A noncontagious chronic disease of the connective tissue classified as a rheumatic disease, scleroderma can be localized or systemic.

Localized scleroderma usually affects the skin, joints and muscles, while systemic may also affect the esophagus, gastrointestinal tract, heart, lung, kidneys and other internal organs.

As the body attacks itself, the skin thickens and hardens, muscles weaken and, as internal organs are affected, many patients with systemic scleroderma die from respiratory failure.

Systemic scleroderma can be further divided into limited and diffuse sclerosis, with diffuse being the most serious form of the disease, Lindsey said.

Only about 50 percent of patients with diffuse systemic sclerosis survive the 10-year mark of their diagnosis. The prognosis is much better for those with the limited form of the disease – 90 percent survive the same time period.

In the systemic form, such as Jeansonne has, there are abnormalities of the small blood vessels, immune system activation and formation of scar tissue in the skin and organs, causing them to harden. Jeansonne had lost more than half of her lung capacity before starting Cytoxan. Her lung capacity is back up to 60 percent now.

The Cytoxan therapy is very intense and is still considered experimental, Lindsey said. As such, it should only be considered for patients like Jeansonne who are seriously ill with systemic scleroderma and are not responding to conventional therapies.

Cytoxan has been used by rheumatologists to treat scleroderma patients in the past, but generally in low doses, he said. Oncologists have more experience with high dose therapy, which can be very toxic, and that’s why Lindsey and Brooks collaborated on Jeansonne’s case.

Heavy doses of Cytoxan were given to Jeansonne in the hospital every day for five days. She suffered serious side effects – nausea, hair loss, low blood counts and infections – and had to stay in the hospital for one month.

However, even while she was still in the hospital, she began to see her symptoms reverse. Her skin visibly softened and lightened and she could once again move without pain. As her lung capacity improved, she could breathe more easily.

That was a little more than a year ago. Jeansonne is still not completely back to normal. She can’t straighten the fingers on her hands, and there are remnants of hardened skin on her arms. She has some residual scar tissue, nerve damage and joint problems.

However, Lindsey and Brooks said they are hopeful that her scleroderma has been arrested and that she will continue to do well. They are also optimistic about the role that Cytoxan and other chemotherapy drugs could play in the treatment of other seriously ill scleroderma patients.

“I’m so thankful that Dr. Lindsey and Dr. Brooks were willing to go out on a limb for me,” Jeansonne said. “I feel like I have my life back. You know I’m starting to see wrinkles in my skin and I’m so excited. Before, my skin was hard and stretched tight. I’m so proud of my new wrinkles.

“I also gave up my handicapped license plate and that was exciting. I thought I was facing a wheelchair before and now I can walk easily again.”

There are an estimated 300,000 people in the United States with scleroderma, according to the Scleroderma Foundation. The disease occurs more often in women, usually in mid- to late-childbearing years. Lindsey has several hundred scleroderma patients under his care.

Symptoms can include abnormal sensitivity to cold, swelling of hands and feet, joint stiffness and contractures, thickening of skin, gastrointestinal problems, dry mucous membranes, oral, facial and dental problems, and kidney, heart and lung involvement.

Traditional treatment is geared toward symptom management, reducing inflammation, pain relief and prevention of contractures.

For more information about scleroderma, visit the Scleroderma Foundation’s Web site at http://www.scleroderma.org or call (800) 722-4673.

Jeansonne is also active in the Baton Rouge Raynaud/Scleroderma Support Group, which next meets at noon Tuesday at Our Lady of Mercy Catholic Church’s Parish Activity Center, 445 Marquette Ave. For more information, call (225) 751-2328.

NEW YORK (Reuters Health) – New research indicates that a
high percentage of patients with migraine or tension-type
headaches experience remission on long-term follow-up.

The findings, which appear in the medical journal
Neurology, are based on an analysis of 549 patients who
participated in a Danish headache study in 1989 and were
reevaluated in 2001. Patient interviews at both time points
were conducted by physicians and standard criteria were used to
diagnose headache.

Sixty-four of the subjects had migraines at the first
evaluation, lead author Dr. Ann Christine Lyngberg, from
Glostrup University Hospital in Denmark, and colleagues note.

At follow-up, 27 of the patients (42 percent) had
experienced remission. The remaining migraine patients included
24 (38 percent) who had just 1 to 14 migraine days per year and
13 (20 percent) who had at least 15 migraine days per year, the
report indicates.

Predictors of a poor outcome at follow-up included high
migraine frequency at the first evaluation and the onset of
headaches at younger than 20 years of age.

As for tension-type headache, 146 subjects had frequent
episodic headaches and 15 had chronic headaches at the first
evaluation. At follow-up, 72 subjects (45 percent) had 0 to 14
headache days per year, 64 (40 percent) had 15 to 179 headache
days per year, and 25 (16 percent) had at least 180 headache
days annually.

Predictors of a poor outcome included chronic tension-type
headache at the first evaluation, coexisting migraine, not
being married and sleep problems.

“Knowledge about the prognosis of migraine and tension-type
headache and information of risk factors and protective factors
is important from both a clinical and a public health
perspective,” the authors emphasize. The present findings
suggest that, in general, the long-term outcomes of these
headaches are favorable, they add.

SOURCE: Neurology, August 23, 2005.

By James Grubel

CANBERRA (Reuters) – The rundown aboriginal protest embassy
in the center of Canberra’s political district is an eyesore
and that’s exactly how the inhabitants like it.

“It sits there in silence, but it’s a pain in the bum for
the politicians,” Michael Anderson, who helped set up the camp
site more than 30 years ago, told Reuters.

Aboriginal leaders set up the protest camp in 1972 on the
lawn in front of Australia’s first national parliament to
support their campaign for traditional land rights, declaring
the collection of tents and campfires as a “tent embassy.”

The tent embassy is Australia’s longest continuous protest
and has been recognized with national heritage status.

But the Australian government has now become fed up with
years of complaints about rowdy camp behavior and, with many
black leaders withdrawing support for the embassy, wants to
clean up the site and end the protest.

Australian Territories Minister Jim Lloyd wants the tent
embassy replaced with some kind of permanent memorial, but its
inhabitants are determined to stay.

“At different times the tent embassy has been hijacked for
different purposes,” said Lloyd, whose portfolio covers the
site.

“In its current configuration, I don’t believe it
represents the aspirations and vision of Aboriginal people,” he
said.

Until 1988, when parliament moved to its new building a
short distance away, the tent embassy was in the foreground of
the sweeping views from the prime minister’s office.

The tent embassy existed on and off for 20 years but became
a permanent fixture in 1992 when an old shipping container
painted with aboriginal designs was placed on the site.

SYMBOL FOR BLACK RIGHTS

A small band of hardy protesters have lived there on a
rotation system ever since.

In its 33 years, the tent embassy has become a powerful
symbol for black rights and has been credited with fostering
new levels of political consciousness and black activism.

Successive governments have tried several times over three
decades to shut down the tent embassy and move the protest on,
but each attempt has led to angry and often violent
confrontations between Aborigines and police.

Many indigenous leaders agree with Lloyd, believing
progress for aborigines now lies in working to resolve problems
rather than through the tent embassy’s confrontational approach
and campaign to overturn Australia’s constitution and laws.

Matilda House, an elder of Canberra’s Ngunnawal aboriginal
people and one of the original tent embassy protesters, is one
of those who has now withdrawn her support.

“I want to see the tent embassy actually do what it was set
up for in 1972,” said House, adding that the embassy should be
pushing new campaigns, such as traditional sea and fishing
rights for indigenous people.

“It is not supporting the issues of people who want to move
on. It doesn’t really represent the whole of Australia in their
issues,” she told Reuters.

Designed to contrast with the expansive embassies of
Canberra’s plush diplomatic district, the tent embassy was
erected to be a daily reminder to politicians as they entered
parliament of the problems faced by Aborigines.

Australia’s 490,000 Aborigines and Torres Strait Islanders
represent about 2.4 percent of the population but make up the
most disadvantaged group in Australia.

Aborigines suffer higher rates of unemployment,
imprisonment, alcohol and drug abuse, and preventable illness.
They also die an average 17 years younger than white
Australians.

EYESORE PROTEST

Anderson, who still regularly visits the site he helped
establish in 1972, believes the tent embassy remains relevant
as a focus of black protest in Australia.

“That embassy stands for something that is wrong in this
country,” he said.

Aboriginal leaders remain angry with the government’s
disregard of spiritual issues, such as Prime Minister John
Howard’s refusal to apologize for past injustices, and its sole
focus on often tough practical solutions for indigenous
affairs.

In the past year, the government has scrapped the elected
indigenous body which had control of spending for health and
housing in aboriginal communities, replacing it with an
advisory board of indigenous leaders hand-picked by the
government.

Anderson said the embassy was a vehicle for both black and
white Australians to express their grievances against the
government, and it would continue to provoke controversy.

Lloyd hopes to have settled on a new plan for the embassy
site by late October.

Anderson, however, is adamant it will stay.

“It doesn’t have a use-by date,” he said. “Until proper
justice and until the government deals with the true issues
then the embassy will always be here, and it will always be an
eyesore.”

SINCE JULY 1, 2004, HELENA Regional Medical Rehabilitation Center has turned away between 25 and 50 patients to ensure it didn’t lose a large portion of its Medicare funding.

The number of patients the 18-bed rehab center turns away is certain to grow as it, like other inpatient rehab facilities across the nation, on, complies with a controversial “75 percent rule” from the Centers for Medicare & Medicaid Services (CMS) in order to hold onto its higher Medicare payments.

The rule is designed to save tens of millions of Medicare dollars each year by rerouting patients to the lowest-cost setting adequate for treating their medical conditions, The rule calls for at least 75 percent of patients at inpatient rehabilitation facilities to be treated for one of 13 diagnoses, including stroke and amputation. The 75 percent threshold is being phased in over three years. In the first fiscal year, which ended June 30, the facilities only had to have 50 percent of their patients meet the diagnostic requirements. For the fiscal year that started last month, though, facilities must meet 60 percent. Starting July 1, 2007, it will be 75 percent.

And that is making inpatient rehab facility administrators nervous.

At the Helena rehab center, 60.25 percent of patients meet the CMS requirement, said Director Kevin Spears.

“You’re turning away a lot of patients,” he said.

Spears estimated the 18-bed facility lost between $500,000 and $1 million in revenue as a result of having to direct patients to other care providers.

The 75 percent rule, which has been on the books since 1984 but rarely enforced, could save Medicare $30 million in 2006 and $190 million in 2008 by directing patients into skilled nursing facilities rather than rehab hospitals.

A day of care in a skilled nursing facility averages about $550 less than a day of treatment ‘in an inpatient rehab facility, according to Steve Miller, senior director of legislative affairs for the American Health Care Association in Washington, D.C., which represents longterm care facilities. The rule should, therefore, bring additional patients and revenue to nursing homes.

But rehab facility administrators are hoping for relief. Legislation has been introduced that would delay the implantation of the rule for two years while Congress and the secretary of health and human services study it.

“I find it completely unacceptable that the Centers for Medicare & Medicaid Services has decided to suddenly hold struggling inpatient rehabilitation centers accountable for a rule that is over two decades old,” Rep. Marion Berry, D-Ark., said in a news release last week. “So much has changed in the fields of medicine over the past 20 years that we have a responsibility to re-evaluate our policies to make sure that they satisfy our goals for providing quality affordable health care.”

Berry is one of 48 co-sponsors of the House legislation that was introduced July 21. A similar bill is pending in the Senate.

But the nursing home industry, on the winning end of the CMS rule, is pleased with the 75 percent threshold and is pushing for it to remain.

“Implementing and enforcement [of] the 75 percent rule will help protect limited Medicare funds and ensure that our nation’s frail, elderly and disabled have access to critical rehabilitative services in the most appropriate care setting,” said Hal Daub, president and CEO of the American Health Care Association, in an April news release.

New Regulations

Inpatient rehab facilities have their own Medicare payment system separate from the ones used for regular hospitals or psychiatric hospitals.

In 2004, the estimated Medicare per-case payment for a patient who had major joint and limb replacement of lower leg was $17,135 to an inpatient rehab facility and $6 $6,165 165 to a skilled nursing facility, according to a Government Accountability Office report released in April.

In 2002, CMS realized its 75 percent rule that had been on the books since, 1984 wasn’t being evenly enforced.

“The 75 percent rule has been around since (1984), what we’re discovering because CMS has never audited on it, … a lot of (rehab facilities) were playing games with the numbers and never actually meeting the 75 percent rule,” Miller said. “And now CMS has decided to crack down on it.”

CMS added three more medical conditions that an inpatient rehab facility could treat to reach the 75 percent threshold.

But that didn’t satisfy the inpatient rehab industry.

“Well, medical practice has changed over the past 20-25 years,” said Paul Cunningham, senior vice president of the Arkansas Hospital Association. “So if that goes into effect, rehab hospitals will have a very difficult time in meetmg those qualifications.”

Cunningham said it’s going to be “almost impossible” to hit the 75 percent mark and “we could see rehab hospitals basically shut down.”

At the Helena Regional Medical Rehabilitation Center, Spears said more marketing will be, done to attract patients that meet one of CMS’ approved 13 medical conditions.

That still might not be enough.

The GAO report said only 6 percent of inpatient rehab facilities were able to meet a 75 percent mark in fiscal year 2003.

“Our analysis of Medicare data shows that there are Medicare patients in (inpatient rehabilitation facilities) who may not need the intensive level of rehabilitation services these facilities offer,” the report said.

Baptist Medical

Baptist Health Rehabilitation Institute in Little Rock has had to deny services to about 200 patients since January, said Greg Crain, vice present of patient services and the administrator at the facility.

“We deliver excellent care, but the rule is going to limit our ability to do so,” Crain said.

Crain said he didn’t know how many patients were going to be turned away this year as a result of the new rules. And it was hard to predict how much revenue the rehab hospital will lose as a result.

For 2003, the latest numbers that were available, the rehab hospital had $55.2 million in patient revenue with $5.5 million in net income. St. Vincent Rehabilitation Hospital in Sherwood had $22 million ‘in patient revenue with $2.2 million in net income in 2003.

Baptist Health’s rehab facility sees about 2,000 patients annually, Crain said.

Crain said physicians at rehab facilities now will have more of a burden to make sure their patient falls within one of the 13 categories the CMS listed for approved treatments.

Crain also said there aren’t any studies to show which type of facility provides the best level of care.

“The government by this rule has really rationed health care for this group of patients,” Crain said. “It’s not a logical rule. It’s just based on numbers, not on individual patients’ illnesses.”

Skilled Homes

A vast majority of the patients who wouldn’t qualify to be treated in rehabilitation facilities will probably end up in skilled nursing centers, said the American Health Care Association’s Miller.

Miller said that across the country inpatient rehab facilities are saying they have lost about 40,000 patients over the previous year as a result of the 75 percent rule.

“Which means those patients are either being seen in a skilled nursing facility or a long-term care hospital or being seen at home,” Miller said.

The skilled nursing facilities, the industry Miller represents, stands to see a lot more patients – and to save Medicare a lot of money.

“That’s the key,” he said. “That’s what CMS is saying: ‘Why are we paying $550 more a day for the exact same patient in the exact same services just because they happen to be in a different setting?'”

Miller said inpatient rehab facilities serve the purpose of taking highintensity patient cases and nursing them back to health.

“The problem is they’ve been cherry-picking patients who don’t belong there,” Miller said.

Copyright Arkansas Business Aug 01, 2005

Sep. 3–SAN FRANCISCO — Ratcheting up pressure on Sutter Health, health care workers at eight Northern California hospitals, including three in the East Bay, say they will strike because little progress has been made in negotiating contracts over the past year.

On Friday, the Service Employees International Union United Healthcare Workers-West set Sept. 13 as the start date for an open-ended strike that could involve as many as 8,000 workers from seven unions. If it goes forward, the strike would rank among the largest ever by health care workers.

SEIU-UHW said 4,500 of its members, including licensed vocational nurses and hospital support staff, would strike unless progress is made at the negotiating table. In addition, the California Nurses Association, representing 3,000 registered nurses at the eight hospitals, said it would support SEIU-UHW workers by striking in sympathy.

Five other unions, including Stationary Engineers, the International Brotherhood of Teamsters, Office & Professional Employees International Union, Unite-Here and the Caregivers and Healthcare Employees Union, which represent another 500 workers, also said they would not cross the picket line.

“We are prepared to begin bargaining around the clock,” said Sal Rosselli, president of SEIU-UHW. “If not, the 4,500 caregivers from SEIU are prepared to strike on Sept. 13.”

Beginning with Alta Bates Summit Medical Center in April, SEIU-UHW contracts at the eight hospitals expired in 2004. The other hospitals where workers will strike include Eden Medical Center in Castro Valley; Sutter Delta Medical Center in Antioch; the two Sutter hospitals in San Francisco — St. Luke’s Hospital and California Pacific Medical Center — Sutter Medical Center of Santa Rosa; Sutter Lakeside Hospital and Sutter Solano Medical Center in Vallejo.

Eden Medical Center chief executive officer George Bischalaney said his hospital would begin preparing for the strike by hiring replacement workers. This is not the first time SEIU has gone on strike, he said.

The last time was in December, when workers struck for one day and then were locked out by the hospitals for another four.

“It’s disappointing for everyone,” Bischalaney said. “I’d rather be in negotiations.”

However, he said he wasn’t sure what will resolve the dispute. “I’m not sure what’s left for us to offer, what else can go to the table,” Bischalaney said.

SEIU-UHW said each of the eight hospitals refuses to accept standards that have been adopted by other large hospital systems, including Kaiser Permanente, Catholic Healthcare West and the Daughters of Charity Health system. The standards include third-party resolution for staffing disputes, a training fund for workers and upgraded retirement benefits.

However, much of the tension between the two sides arises from a push by SEIU-UHW to negotiate with parent corporation Sutter Health and not the individual hospitals. Though Sutter owns 27 hospitals in Northern California, the corporation says it is more appropriate to leave the local hospitals with control rather than create a master contract. On Friday, Sutter Health spokeswoman Karen Garner referred all questions about the strike to the individual hospitals.

An open-ended strike may not be easy for union members, especially those belonging to SEIU-UHW, because they are often lower paid staff members at hospitals.

Rosselli said an SEIU strike fund would contribute $400 a week to each member for an indefinite period of time. He said SEIU-UHW is also talking to unions that have agreed to strike in sympathy about support funds for their workers as well.

It will be hard to forego the wages she makes as a housekeeper at Eden Medical Center, said Debbie Rube, 50. But she’s been saving, and it’s important to stand up to Sutter, she said.

“I look at it like this: If Sutter is our father, don’t you treat all your children in the same way,” she asked. “At Kaiser, you can go from one facility to the next and carry your seniority. If Kaiser can do it, why not Sutter?”

The California Nurses Association said it is supporting SEIU-UHW, even though registered nurses ratified contracts at Sutter hospitals two weeks ago, because nurses are concerned about Sutter’s corporate behavior.

“Sutter has to respect all of its caregivers,” said Chuck Idelson, spokesman for the CNA.

—–

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Copyright (c) 2005, Contra Costa Times, Walnut Creek, Calif.

Distributed by Knight Ridder/Tribune Business News.

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BRUSSELS (Reuters) – The European Parliament is split over
controversial legislation intended to protect workers from
over-exposure to sunshine, ahead of a vote next week.

The 732-member assembly will vote next Wednesday on a bill
which seeks to protect workers from exposure to artificial and
natural forms of radiation which can damage eyes and skin.

Tabloid media in Europe had a field day with the draft
European Union rules during the summer, with Britain’s Sun
newspaper running a ‘Save our Jugs’ campaign amid fears that
barmaids with low-cut tops would have to cover up.

Conservatives and liberals in the EU assembly are against
mandatory rules that would force employers to evaluate the
risks of sunshine to their staff working outdoors. Instead, the
EU’s 25 member states should decide individually whether
employers need to act, spokesmen from the two groups said on
Friday.

But Socialist and Green members want construction workers,
barmaids and other people working outdoors to be informed of
the risks, especially with rising rates of skin cancer.

“We think the directive here is justified. But it’s been
really portrayed in a very distorted fashion,” said a Green
spokesman.

The European Commission, author of the Optical Radiation
Directive, said employers were liable for the health and safety
of their workers and that EU-wide rules were necessary.

“The parliament wants the member states themselves to
decide whether sunlight is a risk or not,” said Commission
spokeswoman Katharina Von Schnurbein.

“That’s totally unacceptable for the Commission.”

But small and medium-sized firms said the rules were costly
and over the top.

“Small firms with employees outdoors, for example caf©s and
construction firms, have neither the resources nor, more
importantly, the expertise to undertake sufficient scientific
analysis,” said European small and medium business organization
(UEAPME) Secretary General Hans-Werner Mueller in a statement.

“These proposals would place an unmanageable burden on
small and medium businesses and could open up a can of worms
with regard to legal liability.”

NEW YORK — Older adults with relatively low levels of a particular blood protein may have a significant decline in muscle strength over time, a new study suggests.

The protein, called albumin, is known to fall to abnormal levels in certain diseases, including kidney and liver disease. In addition, high levels of other, inflammatory proteins in the blood can lower a person’s albumin levels; chronic inflammation in the body is believed to contribute to a number of medical conditions, such as heart disease.

In the new study, older adults with relatively low albumin levels — even within the range of normal — had low levels of muscle strength, regardless of whether they had chronic conditions, such as heart disease and diabetes.

The subjects also showed a greater loss in muscle strength over time, according to findings published in the Journal of the American Geriatrics Society.

It’s uncertain whether increasing an older person’s albumin levels would improve his or her strength, according to the study authors, led by Dr. Bianca W. M. Schalk of VU University Medical Center in Amsterdam, the Netherlands.

Since low protein intake and general malnutrition can trigger a drop in albumin, future studies should look at the effects of special diet regimens on older adults’ albumin levels and muscular strength, they recommend.

The question is an important one, the researchers point out, because slowing age-related muscle loss could make a difference in elderly adults’ health and physical capabilities.

The study included more than 1,000 adults ages 65 to 88 whose changes in albumin levels and muscle strength were followed for at least 3 years. Schalk and her colleagues measured participants’ blood levels of albumin and particular proteins involved in inflammation, and gathered information on their lifestyles and any existing medical conditions.

Grip strength tests were used to gauge their muscle strength.

The researchers found that nearly all of the study participants — 99 percent –had normal albumin levels at the study’s outset. Yet those with the lowest levels relative to their peers had poorer muscle strength. What’s more, these men and women tended to lose more muscle strength over the next 3 to 6 years.

This relationship held true, though it weakened somewhat, when the researchers factored in participants’ health conditions, levels of inflammatory proteins and lifestyle habits like smoking and exercise.

A missing element from the data, Schalk and her colleagues point out, was detailed information on diet. Poor nutrition, they note, through effects on protein synthesis in the body, could spur a decline in muscle strength.

However, the researchers add, since this is the first study to link blood albumin levels to age-related muscle decline, more studies are needed to confirm the relationship and to identify the underlying cause.

SOURCE: Journal of the American Geriatrics Society, August 2005.

Breakthrough Breast Cancer today announce that UK scientists have discovered that a gene ““ named after the James Bond villain Scaramanga ““ can trigger the development of breasts. This has important implications for breast cancer, as reported in the journal Genes and Development.

During the development of an embryo, formation of organs is tightly controlled by specific genes. In the case of breasts, this process controls the development of two breasts in humans but this can go awry, resulting in fewer, extra or misplaced breasts or nipples. However, little has been known about this how this process is governed, until now.

Today scientists at The Breakthrough Toby Robins Breast Cancer Research Centre, at The Institute of Cancer Research, report that a gene called Scaramanga ““ aptly named after the three-nippled villain from the James Bond film The Man with the Golden Gun ““ is involved in triggering breast development.

“Identifying the Scaramanga gene is a real advance in our understanding of the early steps in breast formation. By learning more about this gene and the protein it produces, it will allow us to determine how normal breast development is initiated and, importantly, examine how this is connected with breast cancer,” said Professor Alan Ashworth, Director of The Breakthrough Breast Cancer Research Centre.

By studying abnormal breast development in the lab, scientists at The Breakthrough Breast Cancer Research Centre identified the Scaramanga gene, which regulates the early stages of breast development, and influences the number and position of breasts. The realisation of the importance of their work came when they discovered that the Scaramanga gene produces a protein called NRG3 and that this provides a signal telling embryonic cells to become breast cells. They also showed that a synthetic form of NRG3 was able to initiate the formation of breast cells, confirming the protein’s involvement in this intricate process.

Professor Ashworth continued: “Whilst proteins carefully control the development of breast cells in the embryo, inappropriate signals to breast cells during adulthood by these same molecules may cause breast cancer. We already believe that the protein produced by the Scaramanga gene is linked with breast cancer and the next steps are to study this in more detail.”

Like the gene’s namesake, Scaramanga, 1 in 18 people have an extra nipple**, which can resemble freckles or moles. This is a normal occurrence and does not mean anything is wrong with the person but it’s important that this extra tissue is checked for abnormalities like all breast tissue.

This is just one example of the groundbreaking research, funded by Breakthrough Breast Cancer’s generous supporters, taking place at The Breakthrough Toby Robins Breast Cancer Research Centre. The centre, Europe’s only facility dedicated to breast cancer research, has been producing pioneering research for just over five years. It is based in the Mary-Jean Mitchell Green Building at The Institute of Cancer Research.

In less than five years, the centre has launched The Breakthrough Generations Study ““ the largest investigation ever into the causes of breast cancer, involving 100,000 women over 40 years ““ and has discovered a potential new targeted drug, called a PARP inhibitor, for women with a type of hereditary breast cancer, which is currently in clinical trials.

On the World Wide Web:

Cold Spring Harbor Laboratory

Using a new, more sensitive-testing approach they developed for fungi, Penn State food scientists have found that mushrooms are a better natural source of the antioxidant ergothioneine than either of the two dietary sources previously believed to be best.

The researchers found that white button mushrooms, the most commonly consumed kind in the U.S., have about 12 times more of the antioxidant than wheat germ and 4 times more than chicken liver, the previous top-rated ergothioneine sources based on available data. Until the Penn State researchers developed their testing approach, known as an assay, there was no method employing the most sensitive modern instrumentation and analytical techniques to quantify the amount of ergothioneine in fungi. The researchers say that their assay can be used for other plants, too, not just mushrooms.

Joy Dubost, doctoral candidate in food science, who conducted the study, says, “Numerous studies have shown that consuming fruits and vegetables which are high in antioxidants may reduce the risk of developing chronic diseases. Ergothioneine, a unique metabolite produced by fungi, has been shown to have strong antioxidant properties and to provide cellular protection within the human body.” Dubost detailed the new assay and the amounts of ergothioneine in the most common and exotic mushrooms typically available in U.S. food stores in a paper presented today (Aug. 31) at the 230th American Chemical Society meeting in Washington, D. C. Her paper is Identification and Quantification of Ergothioneine in Cultivated Mushrooms by Liquid Chromatography-Mass Spectroscopy. Her co-authors are Dr. Robert B. Beelman, professor of food science; Dr. Devin G. Peterson, assistant professor of food science, and Dr. Daniel J. Royse, professor of plant pathology.

The Penn State researchers found that among the most commonly consumed mushrooms, portabellas and criminis have the most ergothioneine, followed closely by the white buttons. A standard 3-ounce USDA serving of these mushrooms, about the amount you’d put on a cheese steak or mushroom-topped burger, supplies up to 5 milligrams.

The exotic mushrooms have even more ergothioneine. The same standard serving size of shiitake, oyster, king oyster or maitake (hen of the woods) can contain up to 13mg in a 3-ounce serving or about 40 times as much as wheat germ.

Dubost notes that the levels of ergothioneine do not decrease when the mushrooms are cooked.

In developing their new assay, the researchers adapted an assay used to quantify the amount of ergothioneine in bovine ocular tissue. They used high performance liquid chromatography (HPLC), a UV-VIS detector and mass spectroscopy, instruments normally used in analytical chemistry.

On the World Wide Web:

Penn State