Diagnosis and management of chronic radiation enteritis

Diagnosis and management of chronic radiation enteritis
http://www.aboutcancer.com/radiation_enteritis_utd_807.htm


INTRODUCTION — Chronic radiation enteritis is a complication of radiation therapy for cancer, most commonly for rectal, prostate and pelvic malignancies. It can affect both the large and small intestine, is often progressive, and may lead to a variety of clinical consequences (such as diarrhea, nausea, weight loss, abdominal pain, intestinal obstruction, and perforation) depending upon the extent of the injury. It usually develops six or more months after radiation therapy (mean approximately 5 years, range two months to as long as 30 years. This contrasts with the timing of acute radiation enteritis (characterized by diarrhea and abdominal pain), which develops during or shortly after radiation therapy and resolves within two to six weeks.

The incidence has not been well defined, in part because of the large number of patients who died or were lost to follow-up in major studies involving radiation therapy, and because of the variability in the field size and dose of radiation. One literature review estimated that the incidence ranged from 1.2 to as high as 15 percent in patients with rectal cancer

This topic review will focus on the diagnosis and management of chronic radiation injury to the small intestines and proximal colon. Issues related to the prevention and treatment of chronic radiation proctitis (usually encountered following treatment of cancers of the rectum, cervix, uterus, prostate, urinary bladder, and testes) are presented separately.

PATHOGENESIS — Chronic radiation enteritis usually develops only after large doses of radiation therapy have been delivered (4500 to 5500 cGY); it is uncommon at lower doses. In addition to the dose of radiation, several other predisposing conditions have been described including:

Older age
Combined chemotherapy
Poor radiation technique
Postoperative radiation; in this setting, bowel loops fixed together by adhesions may prolapse into the pelvis, leading them to receive excessive radiation exposure. Adhesions due to past surgical procedures can have the same effect.
Intestinal injury is believed to be related to oxidative damage caused by the formation of free radicals. The end result is an obliterative endarteritis that leads to intestinal ischemia resulting in stricturing with ulceration and fibrosis and occasionally fistula formation. The physiologic consequences may include altered intestinal transit, reduced bile acid absorption, increased intestinal permeability, bacterial overgrowth and lactose malabsorption The resulting clinical manifestations may include nausea, vomiting, lactose intolerance, obstructive symptoms, diarrhea, weight loss, malnutrition, and bleeding (usually in patients with colonic involvement).

The prominent histopathologic features are those of an occlusive vasculitis with diffuse collagen deposition and fibrosis. The arteriolar walls may show a hyaline ring-like thickening and large foams cells beneath the intima. Mucosal ulceration, necrosis and perforation may develop as the disease progresses. Progressive fibrosis leads to stricturing with dilation of proximal segments. The intestinal segments and their associated serosa appear grossly thickened. Telangiectasias may be seen.

The precise mechanisms leading from oxidative damage to the histologic and morphologic abnormalities described above are incompletely understood. Several theories have been proposed, all of which are probably interrelated:

One model suggests that fibrosis develops from the initial mucosal injury
Another theory suggests that fibrosis develops in connective tissues where radiation has caused a decrease in cell turnover and a low rate of proliferation.
A third model focuses on the cellular responses to vascular damage caused by paracrine mediators. The signals leading to the developing of fibrosis are a topic of intensive ongoing investigation.
One study found that intestinal webs forming after radiation therapy demonstrated an impaired vasodilatory response in vitro to acetylcholine treatment. This microvascular dysfunction may lead to the formation of the abnormal tissue response seen in the wall of the intestine post-radiation therapy.
CLINICAL MANIFESTATIONS — The classical features of radiation enteritis are abdominal pain, nausea, vomiting, and diarrhea. Patients with severe disease may develop intermittent, partial, or complete small bowel obstruction

As noted above, bacterial overgrowth may lead to malabsorption and contribute to the nausea, abdominal pain and diarrhea. Bacterial overgrowth should be suspected in patients with intestinal strictures. Another clue may be the development of new lactose intolerance. Nonspecific symptoms include diarrhea, bloating, excessive gas, borborygmi, and nausea. Most such patients have only subtle laboratory or clinical findings pointing toward the diagnosis; thus a high index of suspicion is required. Rare patients with severe malabsorption may present with a more fulminant clinical and laboratory profile

DIAGNOSIS — The diagnosis is usually established by suggestive radiologic findings in patients with compatible clinical features who have a history of prior radiation exposure. The patient's previous radiation treatment record should be reviewed to determine the total dose and distribution of the radiation field. This may help to determine which intestinal segments may have received excessive radiation exposure, information that can be correlated with the radiologic findings and the clinical presentation.

We usually obtain an abdominal CT scan followed by an upper gastrointestinal series with small bowel follow through in patients with suspected small bowel disease. Additional imaging is reserved for patients in whom the diagnosis remains unclear. We generally perform a colonoscopy in patients with suspected colonic involvement.

Upper gastrointestinal series — An upper gastrointestinal series with small bowel follow-through is a useful initial test for evaluating the extent of disease although it is not as sensitive as enteroclysis.

Enteroclysis — Enteroclysis involves the instillation of contrast material (usually administered through a nasoenteric tube) into the small bowel using a pump (making it considerably less comfortable than a standard small bowel follow-through). It provides more detailed visualization of the small bowel compared with a standard upper gastrointestinal series. Suggestive findings include submucosal thickening, single or multiple stenoses, adhesions, and sinus or fistula formation. Its sensitivity and specificity for radiation enteritis have not been well-defined.

CT scan — Computed tomography may show thickening of bowel segments, but the findings are nonspecific. CT may be helpful in narrowing the differential diagnosis, particularly in distinguishing strictures due to radiation enteritis from those arising from abdominal metastases or a local recurrence

CT enteroclysis (in which a CT is performed after instilling contrast into the intestine using a nasoenteric tube) produces superior bowel opacification compared with conventional CT, and may therefore be useful for identifying low-grade or intermittent obstruction (reported sensitivity and specificity of approximately 88 and 82 percent, respectively). However, the technique is still used only in a few specialized centers. Similarly, other improvements in CT imaging of the small bowel (such as three-dimensional imaging) will likely also have a role in diagnosis of radiation enteritis but are not yet widely available

Magnetic resonance enteroclysis — Magnetic resonance enteroclysis permits visualization of the small bowel using similar principles as described above for CT enteroclysis. Initial studies suggest the results are comparable to (and possibly more sensitive than) CT enteroclysis. However, only small numbers of patients have been studied and the technique is not yet widely available.

Enteroscopy — Enteroscopy (peroral endoscopy of the small bowel using specialized endoscopes) has a limited role in the diagnosis of radiation enteritis although it may help to narrow the differential diagnosis. Enteroclysis can be performed following enteroscopy by leaving a tube inserted in the intestine upon withdrawal of the enteroscope.

Capsule endoscopy — There is no published experience with capsule endoscopy specifically for diagnosing radiation enteritis, although there is some clinical experience. However, it should probably not be performed in patients in whom there is a strong clinical suspicion for radiation enteritis because the capsule may become lodged in a strictured segment, requiring surgical removal.

Colonoscopy — Colonoscopy is helpful in evaluating colonic involvement and can also visualize the terminal ileum. Mucosal features consistent with radiation injury include pallor with friability and telangiectasias, which can be multiple, large, and serpiginous; these changes tend to be continuous. Although mucosal biopsies are not diagnostic, they can help to exclude other causes of proctitis such as infection or inflammatory bowel disease.

DIFFERENTIAL DIAGNOSIS — The differential diagnosis of chronic radiation enteritis is broad. Other diagnostic possibilities include post-surgical adhesions, malabsorption syndromes, abdominal metastases, lymphoma, Crohn's disease, infectious, ischemic or ulcerative colitis, and intestinal pseudo-obstruction.

MEDICAL MANAGEMENT — Prevention is the key to avoiding chronic radiation enteritis. Once established, treatment should be as conservative as possible focusing on relief of symptoms. Experience with specific medical treatments has been derived largely from small clinical trials and case series. Approaches used to treat small bowel disease will be summarized below while specific treatments aimed at radiation proctitis are discussed separately.

Dietary recommendations — There does not appear to be a clear-cut diet that reliably alleviates symptoms. A high fiber diet should probably not be recommended specifically since it may worsen diarrhea and urgency. Some patients may develop lactose intolerance, which may be due to bacterial overgrowth, and may improve following antibiotic treatment (see below). Others may require avoidance of lactose. Enteral formulas supplemented with glutamine may have a benefit but studies are limited

Antidiarrheal agents — Judicious use of antidiarrheal agents (such as loperamide) can help improve diarrhea, although it should not be used in patients with suspected small or large bowel obstruction. The efficacy of loperamide was evaluated in a crossover trial involving 18 patients with diarrhea due to radiation enteritis who were randomly assigned to loperamide or placebo for 14 days separated by a 14 day washout period. Loperamide was associated with a significant reduction in the frequency of bowel movements, slower intestinal transit, and improvement in the absorption of bile acids.

Antibiotics — Antibiotics may reduce symptoms in patients in whom bacterial overgrowth has developed. Specific testing for bacterial overgrowth is preferable to empiric therapy. A major drawback to empiric therapy is that treatment may require more than one antibiotic, and repeated and sometimes cyclic treatment. Because antibiotics may be associated with adverse effects, some of which may mimic symptoms of bacterial overgrowth (such as diarrhea and abdominal discomfort), establishing a firm diagnosis is important. This can usually be accomplished with a breath test.

5-ASA drugs — A case report (published nearly three decades ago) suggested a possible benefit from sulfasalazine with or without oral prednisone. There is no large published experience with either of these drugs. Discordant results have been obtained from controlled clinical trials evaluating mesalazine or sulfasalazine in the prevention of acute radiation enteritis

Hyperbaric oxygen — HBO has been used for treatment of refractory foot ulcers in diabetes and in other conditions [39]. The theoretical benefit of hyperbaric oxygen therapy (HBO) may be via inhibition of bacterial growth [40], preservation of marginally perfused tissue, and inhibition of toxin production [41].

A benefit in chronic radiation enteritis was suggested in a case report of a patient in whom 20 treatments over a one month period brought about objective improvements in symptoms and absorption of D-xylose. However, this anecdote did not give the results of long-term follow-up. Other reports have also suggested a benefit for patients with chronic radiation proctitis.

The equipment needed for hyperbaric oxygen treatment is expensive and not widely available. Thus, at the present time, it is not a practical means of treating chronic radiation enteritis outside of centers specializing in this approach, particularly since its effectiveness has not been well-studied.

Parenteral nutrition — A mainstay of the medical therapy of severe chronic radiation enteritis has been total parenteral nutrition (TPN), the success of which is similar for other intestinal disorders requiring TPN. One of the largest series included 54 patients who required home TPN mostly because of intestinal obstruction (27 patients), short bowel syndrome (17 patients), malabsorption (five patients), fistula formation (three patients), and dysmotility (two patients). TPN was initiated a median of 20 months after radiation therapy and was administered for a median of 20 months. Cumulative 5-year survival was 64 percent. Most early deaths were due to recurrent cancer. Similar survival estimates were reached in other series .

SURGERY — As noted above, surgery for radiation enteritis should be avoided if possible because of several inherent difficulties in operating on patients with chronic radiation injury

Diffuse fibrosis and adhesions between bowel loops can make resection technically challenging.
The risk of a leak is high when creating an anastomosis between irradiated tissues. Furthermore, it can be difficult to distinguish healthy tissue for irradiated tissue by gross inspection alone; intraoperative endoscopy may be helpful in this setting, but experienced is limited.
Extensive resection may be required, potentially leading to short bowel syndrome.
Despite attempts at conservative management, approximately one-third of patients progress to the point where surgery is required. Most surgical series of patients treated for radiation enteritis are small; the most common indications for surgery have been persistent ileus, intestinal fistulization, and massive adhesions. Surgical mortality rates are as high as 10 to 22 percent and many patients require more than one laparotomy

An illustrative series focused on 109 patients who underwent surgery during a 10 year period. Five patients died postoperatively (all of whom had undergone resection) while 33 (30 percent) had postoperative complications. Complications were more likely in patients who underwent emergency surgery. Repeat surgery was required in 40 percent of patients during a 40 month follow-up period. Overall survival in patients without a cancer recurrence was 85 percent at year one, and 69 percent at year five.

Strictureplasty may offer a less invasive approach to the management of strictures, but experience is limited. The role of small bowel transplantation in this setting is still being determined; its role, if any, will probably be only in children

SUMMARY AND RECOMMENDATIONS — Chronic radiation enteritis may lead to a variety of clinical consequences (such as diarrhea, nausea, weight loss, abdominal pain, intestinal obstruction and perforation) depending upon the extent of the injury. It usually develops six or more months after radiation therapy (mean approximately 5 years, range two months to as long as 30 years).

The diagnosis is usually established by suggestive radiologic findings in patients with compatible clinical features who have a history of prior radiation exposure. The patient's previous radiation treatment record should be reviewed to determine the total dose and distribution of the radiation field. This may help to determine which intestinal segments may have received excessive radiation exposure, information that can be correlated with the radiologic findings and the clinical presentation. We usually obtain an abdominal CT scan and an upper gastrointestinal series with small bowel follow-through. Further testing with an enteroclysis (standard, CT, or MRI depending upon local expertise) can be performed if the above is unrevealing and clinical suspicion remains.

Management should be conservative, addressing the predominant symptoms.

Patients with diarrhea, abdominal pain, nausea or bloating should undergo breath testing for bacterial overgrowth and treated with antibiotics if bacterial overgrowth is confirmed. Avoidance of lactose may benefit other patients while antidiarrheal agents (such as loperamide) may also be helpful. Loperamide should be avoided in patients with obstructive symptoms.
Patients with intermittent obstructive symptoms may benefit from a low residue diet, although dietary tolerance is variable. Radiologic evaluation may help to identify the strictured segment, information which may be critical should strictureplasty or surgery be ultimately required. The narrowed segment may not always be visible with an upper gastrointestinal series, particularly in patients with intermittent symptoms. Such patients may require enteroclysis as described above.
Despite conservative measures, surgery will be required in approximately 30 percent of patients. This is usually due to persistent ileus, intestinal fistulization, and massive adhesions.
Prognosis is variable since the disease is progressive. Early mortality is usually due to cancer recurrence. Five-year survival is approximately 70 percent in those without cancer recurrence, although many patients continue to have troubling digestive symptoms for the remainder of their lives.

Intensive, ongoing research on mechanisms related to fibrogenesis may eventually produce effective means to prevent or reverse disease progression once it has been established. However, at the present time, prevention during radiation therapy is central to reducing the risk of developing chronic radiation enteritis.

C-Section Adhesions & Scar Tissue

Unfortunately, C-Section adhesions and scar tissue are a very common side effect of having a cesarean birth.


As you heal from your c-section surgery your body will naturally produce adhesions or scar tissue which is the body’s way of replacing the damaged, cut tissues at the incision site, however these adhesions can cause complications.

To clarify, there are really two kinds of scars. There is the incision scar which is the external scar tissue that occurs at the incision site. There is also the adhesions which is the deep scar tissue that occurs in the facial layers of the body.

Both are very different in terms of the problems they can cause and how they are treated.

For example, the external c-section scar is just that, a scar. It is often red and somewhat raised but over time and with care it will disappear. There are even cesarean scar treatments that are very effective in reducing the appearance of c-section scars.


C-section adhesions, on the other hand, occur internally which can adhere or tighten and pull on the abdominal cavity affecting your muscles, organs or even your bones, nerves or arteries. When this happens it can cause things like bowel or digestion problems, back or abdomen pain, it can also become problematic for future c-sections.

Of all the common c-section complications, adhesions and scar tissue can be the most troublesome.

Adhesions begin forming almost immediately after surgery and for many women adhesions are painless, never causing any complications whatsoever, however for others they are not only painful, they can create complications to organs such as the ovaries, uterus, fallopian tubes, bladder or even cause bowel obstruction. Adhesions can also interfere with subsequent births making it harder to get pregnant again.

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FDA Mulls Health Warning on Powdered Gloves

By John Gever, Senior Editor, MedPage Today
Published: February 08, 2011


Health risks associated with powdered medical gloves -- for professionals as well as patients -- may soon be highlighted on their packages, according to the FDA.

In a draft guidance document for manufacturers, the FDA proposed that powdered surgical and patient examination gloves carry a warning that the products may cause health problems ranging from latex allergies to granulomas and adhesions in patients.

The guidance won't be formally adopted until after the agency digests comments on the proposal, which it is accepting through April. Technically, guidance documents are not enforceable, but most manufacturers follow their recommendations scrupulously.

According to the draft, the FDA is reacting to reports on adverse effects associated with powdered medical gloves.

In 1997, an FDA study found a range of allergic reactions that could be caused by these products, which include gloves made of natural rubber latex, nitrile, vinyl, and polychloroprene.

The powder particles -- usually cornstarch -- can carry latex molecules from the natural rubber gloves, triggering or exacerbating allergies in some patients and professionals, the FDA found.

Powders on nonlatex gloves have also been the subject of adverse event reports more recently, the FDA indicated, citing more than 30 studies. These include impaired wound healing, inflammation, granulomas, and adhesions in patients.

Some have shown that hospitals switching to unpowdered gloves have reduced allergy development and respiratory problems, the FDA added.

The agency also noted, however, that "this has not been a universal finding," and the studies have had significant methodological limitations.

Nevertheless, the agency is proposing that manufacturers include the following warning on glove boxes:

"Powdered gloves may lead to foreign body reactions and the formation of granulomas in patients. In addition, the powder used on gloves may contribute to the development of irritant dermatitis and Type IV allergy, and on latex gloves may serve as a carrier for airborne natural latex leading to sensitization of glove users."

If the guidance is adopted, manufacturers are urged to place the warning on product labeling within six months.

What Patients Deserve to Know: Even Vegas has to Publish Its Odds

By Donna Smith

Since millions of American patients face medical debt they didn’t know they’d have – and many if not most of them purchased insurance to protect against that debt – it seems logical to me that patients should be fully informed up front of the financial risks they are taking on when they seek medical care. Doctors and others providers should publish and post in their offices their methods of debt collection and the numbers of patients they sue in an average practice year. They can put the disclosures of medical debt collection practices right next to the little signs that tell patients they must pay their co-pays prior to receiving medical care.

I shared the idea with my University of Chicago educated son, and he liked it. He said, “Even Vegas has to disclose the odds of winning.” True enough. Even those who love the market economy like to know as much as possible about their financial entanglements before they enter them.

Disclosure. Disclosure. Disclosure. (Much like the old real estate advice – location, location, location.) Financial. Debt collection practices. Health condition outcomes.

So, along with the releases and privacy statements and risk assignment forms I must sign before I am accepted as a patient, providers should also publish their outcomes evidence as well. How am I to know if a given provider is just good buddies with the referring physicians or if they truly have a success record with the condition for which I require care?

I’d feel better about reform that promised those things than I do about a reform measure that simply forces me to purchase the defective financial product sold as private health insurance. Private health insurance is marketed to me to protect my health and wealth, and yet it may or may not do either. It’s a crap shoot.

Did you know some medical providers in Pennsylvania go to what’s known as “collectors’ universities” to learn how to collect their medical debt from the families of deceased patients? They study two legal documents offered by the collection experts: the “Doctrine of Necessities” and “Collecting from the Deceased.” Ouch. Imagine that after your loved one’s for-profit private insurance company fails to pay all the bills when a child or spouse or parent dies. And Pennsylvania providers are no different than many others around the nation. Collecting medical debt is big, big business.

So regardless of what this Congress does or what this President celebrates in the Rose Garden framed by the billowing cherry blossoms, I’ll still be slugging it out in the front offices of providers, at the admissions desks in hospitals and at the pharmacy counters to try to secure the care I need and pay for. Nothing has been done to improve my chances of getting what I bargained for as a patient. I am to accept on good faith what the providers secure as a legal guarantee from me.

I want a single standard of high quality care through progressive financing. I want to be able to choose the care that is high quality. I simply cannot do that unless and until my rights as a patient are protected. And we are a long way away from that day. Under an improved Medicare for all system, I would be saved from the terrible loop that is the medical collection system in this nation. I’d still want to know health outcomes data, but that would be far easier to obtain and track. Wow, imagine that.

Should gamblers playing slot machines really be given the legal right to know pay-out odds in a nation that thinks patients have no right to knowledge of results expected from their medical care providers? Surely, reputable providers could not object to that sort of patient or citizen empowerment. But wait. A lawyer friend of mine from Colorado tells me that hospitals and many doctors could hardly be less cooperative in talking about this topic. Big surprise.

The day will come when patients will be the center of this debate. It has not come yet. This Congress and this administration have never put our interests first, so this effort was flawed from the start. Because the improvements I need to see as a patient are nowhere to be found in this mess, I understand why people lose interest in the fight. The disconnect between what we need and what we are getting from this round of health reform effort as patients and as citizens is a chasm too deep.
Link to article

Laparoscopic versus open surgery in small bowel obstruction.

So no one's even bothered!.....
________________________________________

Cochrane Database Syst Rev. 2010 Feb 17;2:CD007511.

Laparoscopic versus open surgery in small bowel obstruction.
Cirocchi R, Abraha I, Farinella E, Montedori A, Sciannameo F.

Clinica Chirurgica Generale e d'Urgenza, Azienda Ospedaliera di Terni, Terni, Italy, 05100.

BACKGROUND: Acute intestinal obstruction is one of the most common surgical emergencies. The small bowel obstruction (SBO) is the site of obstruction in most patients (76%) and adhesions are the most common etiology (65%). Laparoscopy in SBO has no clear role yet as it may have a therapeutic and diagnostic function. In some settings laparoscopic or laparoscopy-assisted surgery is considered feasible and convenient more than conventional surgery for SBO; however little is known if laparoscopic or laparoscopy-assisted surgery is more suitable with respect to open surgery for patients with SBO. OBJECTIVES: The aim of this systematic review is to assess whether laparoscopic or laparoscopy-assisted surgery is feasible and safe for acute SBO, and whether laparoscopic and laparoscopy-assisted surgery present advantages compared to open surgery in terms of short-term and long-term outcomes. SEARCH STRATEGY: We searched for published randomised and prospective controlled clinical trials without language restrictions using the following electronic databases: Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE (1950 onwards) and EMBASE (1980 onwards). SELECTION CRITERIA: Randomised controlled trials and non randomised controlled prospective trials evaluating laparoscopic and laparoscopy-assisted surgery versus traditional open surgery for acute SBO were considered. DATA COLLECTION AND ANALYSIS: We conducted the review according to the recommendations of The Cochrane Collaboration and the Cochrane Colorectal Group as well, using Review Manager 5 to conduct the review. MAIN RESULTS: No published or unpublished randomised controlled trials or prospective controlled clinical trials comparing laparoscopy with open surgery for patients with SBO were identified. AUTHORS' CONCLUSIONS: Although data from retrospective clinical controlled trials suggest that laparoscopy seems feasible and better in terms of hospital stay and mortality reduction, high quality randomised controlled trials assessing all clinically relevant outcomes including overall mortality, morbidity, hospital stay and conversion are needed.

PMID: 20166096 [PubMed - in process]
http://www.ncbi.nlm.nih.gov/pubmed/20166096?itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_RVDocSum&ordinalpos=14

Rep. John Murtha dies after surgery complications

(CNN) -- Rep. John Murtha of Pennsylvania, a longtime fixture on the House subcommittee that oversees Pentagon spending, died after complications from gallbladder surgery, according to his office. He was 77.

The Democratic congressman recently underwent scheduled laparoscopic surgery at National Naval Medical Center in Bethesda, Maryland, to remove his gallbladder. The procedure was "routine minimally invasive surgery," but doctors "hit his intestines," a source close to the late congressman told CNN.

Murtha was initially hospitalized in December and had to postpone a hearing with Defense Secretary Robert Gates on the administration's strategy in Afghanistan. The congressman returned to work after a few days in the hospital and helped oversee final passage of the 2010 defense appropriations bill.

More:http://www.cnn.com/2010/POLITICS/02/08/john.murtha.obit/index.html?hpt=T2

Surgical gel gets blame for pain

By RUTH HILL - The Dominion Post


NATALIE SLADE/Dominion Post
SCARRED: Carla Gardiner had to have a four-hour operation to remove the scar tissue caused by anti-scarring gel during her initial surgery
Related Links'Scarring more painful than original illness'


A surgical spray gel that may have left hundreds of New Zealand women with painful internal scarring and fertility problems has been modified but doctors have not been told why.
Wellington gynaecologist Hanifa Koya, who first raised concerns about Confluent SprayGel in 2005, accuses the manufacturer of evading its responsibility toward "millions of women" worldwide who have been potentially injured by the gel.
The blue gel renamed SprayShield was supposed to prevent scarring during gynaecological surgery, but left some women with their reproductive organs "super-glued" together.
Up to 1200 New Zealand women were treated with the gel between 2004 and 2008.
Mrs Koya has learned that Covidien, which manufactures and distributes the gel, has replaced the suspect dye, methylene blue, with a vegetable dye. "The fact they withdrew it voluntarily suggests they know there was something wrong with it."
She began using the gel in October 2002, but stopped in April 2006 after her rate of repeat keyhole laparoscopies went from under 2 per cent to 10 per cent. Since switching to an alternative product, she has not repeated any laparoscopies, but patients were still returning from four years ago with "sheets of scarring".
She complained to American manufacturer Confluent Surgical and wrote repeatedly to MedSafe the Government's drug safety agency and professional bodies asking for action, but says she was stonewalled.
Medsafe investigated but accepted the manufacturers' assurances that the product was safe and that clinical trials were continuing.
"[But] methylene blue has never been tested on humans and the gel has never been approved for use in the United States," Mrs Koya said.
At the World Congress on Endometriosis in Melbourne last year, Mrs Koya was appalled to meet other specialists who had stopped using the gel because of complications.
ACC has not accepted any claims by victims for treatment injuries. Most of her patients' repeat operations which cost between $6000 and $12,000 have been covered by insurance, and she has waived her own fee for those with partial cover.
"That's a huge cost to the health system, it leads to increased insurance premiums and makes it harder for people to have their claims accepted. Ultimately it's patients who pay the price."
Health Minister Tony Ryall declined to be interviewed, referring comment to Medsafe.
Medsafe group manager Stewart Jessamine said because the gel was classified as a medical device under the Medicines Act rather than a drug, the legislation did not allow Medsafe to assess its safety or efficacy before it entered the market.

"However ... it has been assessed to very high standards by medical device regulatory authorities in Europe and Australia."
Some studies had showed increased rates of complications, including those described by Mrs Koya, he said. "However, there was no evidence that the rate of adverse effects was significantly different from that expected historically."
TIMELINE
2001: American-made Confluent SprayGel approved for use in Europe and subsequently Australia and New Zealand but not the United States.
OCTOBER 2002: Wellington gynaecologist Hanifa Koya begins using the gel.
2005: Mrs Koya first notices patients coming for repeat surgery and contacts the company, which tells her the product is being monitored in clinical trials.
APRIL 2006: Mrs Koya stops using the gel because of ongoing concerns. She alerts the College of Obstetricians and Gynaecologists and the Centre for Adverse Reaction Monitoring. Both refer her to Medsafe, the Government's drug-safety body.
FEBRUARY 2007: Mrs Koya complains to Medsafe.
NOVEMBER 2007: After reviewing international literature, Medsafe finds some reports of complications similar to those described by Mrs Koya. It asks the company include "additional precautions" on packaging but says the product is still safe.
DECEMBER 2007: Mrs Koya writes to the college again with her concerns.
JANUARY 2008: The college says Medsafe appears to have investigated the issue thoroughly.
FEBRUARY 2008: An affected patient talks to The Dominion Post and Mrs Koya speaks publicly about her concerns.
APRIL 2008: Mrs Koya writes to Medical Assurance Committee of the college.
JUNE 2008: Pharmaceutical company Covidien Tyco takes over distributing the gel in New Zealand from Intermed Medical.
AUGUST 2008: Mrs Koya writes to the health and disability commissioner, but is told the matter is outside the commission's jurisdiction.
OCTOBER 2008: Covidien relaunches the product as SprayShield Adhesion Barrier, which uses a vegetable dye instead of chemical dye methylene blue. The gel is available in Europe, the Middle East, South Africa, Australia and New Zealand but still not approved for use in the US.
http://www.stuff.co.nz/national/health/2480461/Scarring-more-painful-than-original-illness

The fate of Stacey Mullens

Stanford Surgeon's Procedures Raise Ethical and Legal Red Flags
Supporters say Camran Nezhat is a miracle worker -- critics call his operations bizarre and barbaric...

With a white surgical mask dangling rakishly below his chin, Dr. Camran Nezhat looks every bit the part in his promotional video: medical pioneer, gifted surgeon, millionaire inventor of operating room tools. The Stanford clinical professor, recruited from his lucrative Atlanta practice, is a rainmaker for the university's medical center and obstetrics and gynecology department. Since he arrived at Stanford in 1993, he has brought patients, prestige, and scores of surgeons to study at the Stanford Endoscopy Center, which he directs.
But along with his brother gynecologists, Drs. Farr and Ceana Nezhat, he has also brought trouble to this elite enclave of high-tech medicine.
Trailing him to Stanford are allegations of reckless and unethical medical conduct. Critics accuse the Nezhats of performing a bizarre and dangerous medical experiment on the rectums of vulnerable female patients and of falsifying data reported in medical journal articles.
In the past five years, 20 doctors and surgeons across the country have signed statements of serious concern about the Nezhats' surgeries and published research and have called for an investigation.
''In my experience in the fields of law and medicine, I can't imagine a group of men who have crossed the line in more ways in the field of bioethics than the Nezhats,'' said Andrea Scott, a Los Angeles attorney and bioethicist.
And if the allegations against the Nezhats are true, soon top Stanford administrators may face troubling questions about the extent to which they heeded repeated warnings about the Nezhats and investigated the charges against them.
While the American College of Gynecology's code of ethics requires members to report questionable medical practices, a top Stanford official threatened at least one doctor with a lawsuit if he continued to criticize the Nezhats.
''There are serious, serious problems going on at Stanford,'' said Dr. Tom Margolis, a former Stanford Medical School professor who has signed a sworn affidavit charging the Nezhats with misconduct. ''Certain people are covering this up because there is a hell of a lot of money going to Stanford because of the Nezhats.''
The Nezhat brothers have declined to be interviewed. Through their Atlanta attorneys, they deny any wrongdoing and question the motives of their accusers, citing professional rivalry and economic competition. Stanford officials say they have thoroughly investigated and rejected allegations of scientific fraud.
Camran Nezhat is embraced by a large cadre of supporters, including Stanford colleagues and patients, who admire him personally and are awestruck by his abilities in the operating room.
''People like (Nezhat) are a rarity,'' said Salinas gynecologist Dr. Rene Charles. ''I'd compare him to Michelangelo, in terms of his surgical skills.''
In a letter of support sent to The Chronicle, 39 Stanford nurses and other health-care staff members describe Nezhat as a worker of ''miracles'' who takes cases ''others have given up on.''
Yet doubts about the Nezhats date back well into the 1980s, when Camran emerged in Georgia as a pioneer in the nascent art of laparoscopic surgery.
And they have been rekindled by recent developments in an astounding malpractice case that has been languishing in Atlanta courts for six years.
That case could determine once and for all whether the Nezhats are the pioneering surgeons they claim to be or whether they catapulted their careers to Stanford on the basis of a dangerous and grotesque medical fraud.
BUILDING A PRACTICE, 1988
Camran Nezhat and his brothers grew up in prerevolutionary Iran, where each attended medical school. Camran emigrated to the United States in 1974 and completed his obstetrics and gynecology residency at the State University of New York at Buffalo.
In 1978, he received a two-year reproductive endocrinology fellowship at Medical College of Georgia in Augusta. Farr and Ceana followed their older brother to Augusta and eventually joined Camran's growing practice in Atlanta.
During the 1980s, while practicing at Atlanta's Northside Hospital, the Nezhats began to develop a reputation for their skills in laparoscopy, a type of surgery in which laser scalpels, miniature cameras and long-stemmed instruments are worked inside the body through dime-sized incisions.
They published scores of articles in medical journals, claiming a remarkable series of ''surgical firsts.'' They also developed a number of ingenious instruments for the laparoscopic operating room. A company they co-founded, American Hydro-Surgical Instruments Inc., eventually sold for $40 million.
Their specialty was treating endometriosis, a painful ailment afflicting an estimated 5 million American women. It is caused when cells that make up the lining of the uterus migrate and bind to other parts of the abdominal cavity, swelling with the monthly menstrual cycle, sometimes causing debilitating pain. The condition is often linked to infertility.
Northside Hospital began promoting the Nezhats, hiring a public relations firm to spread the word about the doctors and their accomplishments. Camran was featured in Newsweek and the Chicago Tribune, and on MSNBC, CNN, ABC's ''20/20'' and elsewhere.
The brothers garnered a reputation as some of the world's foremost innovators of laparoscopic surgery, attracting cash-paying patients from around the globe.
THE MULLEN CASE, 1991
Suffering from endometriosis, 28-year-old Stacey Mullen flew from Southern California to Atlanta's Northside Hospital in 1988 to be operated on by Camran Nezhat. The surgery was quick, the pain was gone, and Mullen was elated as she walked out of the hospital the next day.
''I was ready to name my firstborn after Camran Nezhat,'' she said.
But, as often happens, the endometriosis and the pain returned. And in December 1991, Mullen flew back to Atlanta for what she thought would be another ''quick little surgery.''
The surgery, however, was neither little nor quick.
Camran and his brother Farr, with colorectal surgeon Dr. Earl Pennington assisting, spent hours using laparoscopic techniques to cut Mullen's colon and rectum free of nerves, blood vessels and connecting tissue. Her ''mobilized'' rectum was pulled inside out through her anus, and suspected endometrial tissue was removed. Her patched-up rectum was then pushed back inside.
Then the complications began.
Hours after surgery, part of her colon dropped out of her body as she sat on the toilet. For months, she suffered from extreme constipation. Sometimes she burped up her own feces.
Mullen never regained normal use of her bowel. Eventually, she received a colostomy and must insert a tube into an opening in her side to go the bathroom.
In December 1993, after nearly two years of continuing pain, she filed a malpractice suit against the Nezhats. ''Those bastards ruined my life,'' she said.
THREE ARTICLES, 1993
Shortly after taking Mullen's case, attorney James Neal discovered two medical journal articles that the Nezhats and Pennington had published after Mullen's operation.
The first appeared in Fertility & Sterility in May 1992, describing a single case using the new pull-through procedure for treating rectal endometriosis. ''As with all new procedures,'' the article said, ''there are no data to establish its safety.''
The second was published in the September 1992 issue of Surgical Laparoscopy & Endoscopy. It detailed a series of 16 rectal surgeries, similar to Mullen's, performed in late 1991 and early 1992 - the period during which her surgery took place.
Yet Mullen's case - and her complications - were not mentioned.
The article listed only a single complication: The doctors had to perform traditional open abdominal surgery in order to complete the suturing of one patient's bowel.
''This procedure has been performed safely in this initial series,'' the Nezhats wrote, and they claimed fewer problems than would be expected with regular open abdominal surgery.
The Nezhats aggressively publicized the ''success'' of the new procedure. It was touted by Ethicon Inc., the Johnson & Johnson subsidiary that made the instruments the Nezhats had used. ''For the estimated 185,000 women who suffer from endometriosis of the rectum, this new advance provides them with relief from the digestive symptoms,'' the company said.
At a 1991 American Fertility Society meeting in Orlando, and a 1992 convention of the American College of Obstetricians and Gynecologists in Las Vegas, Ethicon promoted their instruments and the Nezhats, even including a video of the surgery.
But skepticism about the Nezhats and their procedure was beginning to grow. The lack of complications did not make sense for such radical bowel surgery, doctors said. Some surgeons who viewed the promotional video were puzzled: They could not see evidence of endometriosis.
Stories began circulating in the surgical community around Atlanta's Northside Hospital. The medical journal articles said the average operating time for the surgeries was three hours, but during the time of the study, the Nezhat operating room had been burning lights deep into the Georgia night.
Then Neal discovered a third journal publication, written by one of Nezhat's Atlanta colleagues and published more than a year after Mullen's operation.
The article in Surgical Endoscopy described a ''pilot'' study testing the same procedure on pigs in order to assess its safety on humans.
''Some damage to the sphincter might occur,'' the authors wrote, but the long-term effects were unknown: The pigs were ''sacrificed'' before they awoke from anesthesia.
Neal and Mullen were stunned: Not only had the Nezhats omitted Mullen's case from their series - and in doing so did not report her complications - they apparently had tried out the new procedure on her and other women before it was tested on pigs.
Nezhat attorney David Walbert said the pig study ''had nothing whatever to do with the safety and efficacy'' of the human surgery described in the medical journals. The purpose of the pig experiment, he said, was to determine whether the procedure was suitable for treating cancer.
'BARBARIC,' 1993
When Neal began contacting medical experts about Mullen's surgery, many sent him letters and affidavits calling the operation radical and experimental; they characterized it as ''bizarre'' and ''barbaric.'' It resembled a cancer surgery that had been discredited years before, after complication rates as high as 50 percent were reported.
The surgery had not been vetted before a Northside Hospital Institutional Review Board, the usual requirement for an experimental procedure.
''Normally you go before an IRB, come up with scientific background, present a plan, torturous documentation, nine pages of informed consent, and you cannot charge for it,'' said Ohio general surgeon Dr. Francis Barnes.
Mullen and her insurance company, however, were billed $9,900 for the rectal surgery. She eventually ran up more than $1 million in additional medical expenses as a result of the operation, according to Neal.
Neal also learned that Mullen - and possibly four other women whose cases were included in the Nezhats' articles - had signed an unusual document, recently created by the Georgia legislature. It was called a ''waiver of informed consent,'' and it set aside a patient's right to detailed information about a surgery.
''This is incomprehensibly unethical,'' said Arthur Caplan, director of the University of Pennsylvania Center for Bioethics and one of the nation's foremost medical ethicists. ''You can no more sign away your right to informed consent than you can voluntarily sell yourself to slavery.''
''I never knew I was signing such a document,'' Mullen said. ''I thought it was a regular consent form.''
Yet the most disturbing discovery was made in Mullen's own medical records. In his operative notes, Camran Nezhat wrote: ''There was evidence of severe endometriosis of the rectum.''
But Mullen's pathology lab report disclosed that there had been no endometriosis on the wall of her rectum at all - just a few cells in the adjoining fat. The surgery had not been necessary in the first place.
16 MEDICAL RECORDS
Neal went to court and demanded to see the medical records of the 16 other patients the Nezhats had operated on in Georgia, convinced they would show complications, more waivers of informed consent, and surgical data different from what was reported in the Nezhat articles.
But the Nezhat legal team refused to turn them over, citing privacy concerns of other patients - at least 10 of whom signed affidavits opposing any release.
Mullen was given the waiver form by mistake, they explained, and she was told about the procedure's risks. Medical experts for the Nezhats also insist that the rectal surgery was not experimental, so no Institutional Review Board process was required.
''In my opinion, the surgery performed on Mary (Stacey) Mullen was a necessary procedure and would not require any special consent form for experimental surgery,'' said Dr. Robert R. Franklin, a clinical professor in the department of obstetrics and gynecology at Houston's Baylor College of Medicine.
The Nezhat lawyers also argue that Mullen's rectal surgery did not cause her bowel problems. ''She reported constipation before the procedure,'' said Walbert.
THE FIRST WARNING, 1993
In the early 1990s, Stanford Medical School's department of obstetrics and gynecology was in trouble. Despite the school's lofty reputation, the department was not fully accredited.
The Chicago-based Accreditation Council for Graduate Medical Education demanded more ''surgical volume'' before it would upgrade the program's ''provisional'' status.
Yet when Dr. Nick Spirtos heard that Stanford was recruiting the Nezhats, he could not believe it.
Spirtos is a Palo Alto gynecological oncologist with an august reputation of his own. Like the Nezhats, he is a clinical professor, which means he serves on the school's voluntary teaching faculty with surgical privileges at the medical center. He also holds the elected post of deputy chief of the obstetrics and gynecology department.
During the past nine years, he has become a leading critic of the Nezhats and their Stanford defenders.
''I think everything they've written is fraudulent,'' said Spirtos, whose office is just one floor below the Nezhats' in an upscale medical office building near Stanford. ''I don't think they should be allowed to practice medicine.''
Spirtos had traveled with colleagues to a gynecology convention in Florida to see the 1991 presentation by Camran and Farr Nezhat sponsored by Ethicon. The program included videos of two new Nezhat operations, one of them showing the rectal procedure that would be performed two months later on Mullen.
''We couldn't believe what we saw,'' Spirtos said, noting that there was no evidence of endometriosis. ''The surgeries didn't make any sense.''
But before they could quiz the Nezhats about their presentation, Spirtos recalled, the Nezhats left the podium, refusing to answer questions.
Two years later, after studying their journal articles, he warned university administrators not to bring them to Stanford. Spirtos argued that the Nezhats' published data were simply too good to be true.
But Spirtos said his advice was ignored.
''It was a perfect marriage,'' he said. ''The Nezhats had all the dough in the world but no title. And Stanford needed desperately to have surgical volume to legitimize their (obstetrics and gynecology) department.''
NEW TROUBLE, 1993
Within two years of the Nezhats' arrival in Palo Alto, Camran became director of the new Stanford Endoscopy Center for Training and Technology. And Ethicon, which had retained Nezhat as a surgical investigator, agreed to provide a $125,000 annual grant to the center.
Quickly, the Nezhats began pairing up with surgeons outside their immediate discipline - including specialists in cancer, heart and brain surgery - with the goal of expanding the use of minimally invasive surgical techniques.
The practice troubled Spirtos, and when he learned that Camran Nezhat intended to operate on a patient of one of Spirtos' medical partners, he wrote in protest to Dr. Mary Lake Polan, the chief of the obstetrics and gynecology department.
The patient was a 74-year-old woman who had undergone extensive surgery for the removal of pelvic cancer, and Spirtos told Polan that the patient's cancer had spread so extensively that laparoscopic surgery would be useless.
''Certainly, (Nezhat) has no experience in this area (treating cancer), and it seems to me serious patient care issues are being placed on the back burner in your headlong rush to promote the Nezhats,'' he said in a 1993 letter to Polan.
Despite Spirtos' protests, Nezhat and Stanford cancer surgeon Dr. Nelson Teng went ahead with the operation.
The patient was on the operating table for seven hours and was hospitalized for seven days afterward. Her bladder and bowel were punctured during the operation, Spirtos said, and the doctors could not remove all the cancer. In his report to the university's ''quality assurance'' review committee, Spirtos charged that Nezhat, credentialed as a gynecologist, was performing cancer surgeries, a specialty that requires years of extra formal training. He also laid out four other Nezhat cancer cases for the quality assurance review committee.
''No other hospital would allow a gynecologist to perform (cancer) surgeries,'' said Spirtos.
But his hope for a quick review of the five cases soon faded. ''Stanford sat on those cases for years,'' he said.
NEZHAT'S AFFIDAVIT, 1994
Meanwhile, Mullen and her attorney continued to press for the release of the files on the 16 other women who had undergone the rectal procedure. And the Nezhats continued to refuse.
In a sworn 1994 affidavit, Camran Nezhat declared it would disrupt his practice for months if he were ordered to produce records demanded by Mullen's legal team.
He described a filing system with 20,000 patients, each listed only alphabetically, with no index, no computer database and no cross-referencing by type of treatment, surgery performed, or journal publication.
''I would . . . have to manually review every single patient record . . . to determine whether the record referenced a patient whose procedure was the subject of a journal article,'' he testified.
The affidavit shocked Nezhat's critics, who say it has cast a pall on the validity of the Nezhats' research ever since.
''I've been doing this kind of research for 25 years. There is a substantial problem if you cannot link patient records to publications,'' said Dr. David Grimes, former chief of obstetrics and gynecology at San Francisco General Hospital, who briefly served as a paid expert to Mullen's legal team.
How, asks Grimes, can the Nezhats publish extensive studies based on old charts and old data involving hundreds of patients over many years if those patients' files are not indexed or cross-referenced?
Grimes was not the first doctor to question the Nezhats' research. Long before they publicized their controversial bowel surgery, competitors and collaborators alike were skeptical of the brothers' claims of surgical firsts and problem-free procedures. In 1987, Dr. Harry Reich, a world-renowned laparoscopic surgeon at New York's Columbia-Presbyterian Medical Center, agreed to collaborate with Camran Nezhat on a surgical study of 105 tubal pregnancies.
But Reich was bothered by Nezhat's repeated failure to share his data on 40 patients to be included in their article in the Journal of Reproductive Medicine.
''So we had to delete the data from the paper,'' Reich recalled.
The Nezhats' lawyers say Reich never requested any data that were not provided.
In 1990, a Nezhat report in the journal Obstetrics and Gynecology also raised eyebrows. The Nezhats stated they had performed 4,000 laparoscopic surgeries without injuring a ureter, the tube connecting the kidney and bladder.
Their claim drew a sarcastic response from three Yale University doctors: ''The authors are to be congratulated. . . . Either these surgeons had other complications, perhaps as serious, or they possess an unbelievably high level of skill and judgment.''
Other articles in which the Nezhats claim to have reviewed thousands of old cases include:
-- A 1995 textbook article describing 214 complications among 6,949 cases in Atlanta and Stanford from 1982 to 1993.
-- A 1996 medical journal report of severe urinary tract endometriosis in 28 women among 2,226 treated for endometriosis from 1989 to 1994.
-- A 1997 study examining 5,300 surgeries dating back to 1988, counting up 11 hernias caused by insertion of the laparoscope.
Atlanta attorney Walbert scoffs at accusations of medical fraud. ''Many, many surgeons'' have conducted research with the Nezhats, he said. ''Those who have any knowledge have never claimed there was anything 'bogus' about any of the reports.''
Dr. Sally Tazuke, a Stanford reproductive endocrinologist who has worked with Camran Nezhat frequently, said his reported complications are low because he is exceptionally good at what he does - even while taking on the riskiest cases. ''If I were a patient, I would sign up with him. I'd send any family member,'' she said.
Skeptics say the stakes are high. Dr. Thomas Lyons, an Atlanta gynecological surgeon who believes the Nezhats have published journal articles with phony data, said medical fraud can lead unsuspecting doctors to hurt their patients.
''This is as dangerous a situation as you can run into in medicine, because people may be making medical decisions based on something that doesn't exist,'' he said.
If someone ever questioned the veracity of his own data, Lyons said, ''The first thing I would do is throw that data right in their face. . . . The best defense in the world is the truth.''
NEAL'S LETTER, 1995
In January 1995, Mullen's attorney, James Neal, wrote to Stanford, alerting the university to the allegations his legal team was making against the Nezhats. As a former hospital counsel himself, he said he thought they would appreciate a copy of the Mullen lawsuit.
''I feel that your institution should have the opportunity to evaluate these matters . . . given your understandable and overriding concern for the patients within your institution,'' Neal wrote.
But Stanford took no action.
Instead, Margaret Eaton, a university lawyer, forwarded the letter to Nezhat's attorney in Atlanta, with a note saying that ''we do not intend to respond to this letter, nor are further communications from Mr. Neal welcome.''
In June 1995 the Accreditation Council for Graduate Medical Education approved full accreditation to Stanford.
ALLEGATIONS, 1996
A year later, Neal sent Stanford a thick package of documents, laying out in more detail the charges against the Nezhats and asking Stanford to investigate.
Dr. Richard Popp, Stanford's senior associate dean for academic affairs, said Neal provided a ''massive amount'' of what he called ''disorganized'' information.
Popp finally opened an inquiry into the charge of scientific misconduct. But university officials contend that by that time, some of the allegations, including Neal's claim of medical journal fraud, had been thrown out by the Georgia courts.
Neal, who freely admits that he has become obsessed with exposing the Nezhats, was running up a list of legal setbacks. In his dogged pursuit of the Nezhats, he was building a reputation as a crank.
He was disqualified from the malpractice case by a Georgia judge in 1995 for ''unethical behavior'' and could no longer represent Mullen. After a federal judge last year tossed out his attempt, on behalf of another client charging malpractice, to use racketeering charges against the Nezhats, Neal was charged with contempt of court. The judge also assessed $384,000 in ''sanctions'' against the plaintiff and her remaining attorneys. The sanctions are on appeal.
Neal denies the unethical conduct allegation, and the contempt of court charge was recently dropped. The only thing he is guilty of, he says, is aggressively representing his clients against institutions willing to look the other way.
''These guys are bad doctors, some have even said evil, and they have to be stopped,'' he said.
WITNESS, 1996
Shortly after Dr. Tom Margolis joined Stanford as an assistant professor and chief of pelvic surgery, Farr Nezhat invited the newcomer to watch him perform a complex laparoscopic procedure.
During the operation, Nezhat cut the patient's ureter. Margolis, who had also served as director of urogynecologic/pelvic surgery at Northwestern University Medical School, assumed it was an accident, a known but unwelcome complication of the difficult surgical technique. He stepped in to assist Nezhat in repairing it.
But a short time later Margolis learned that, in a post-operative review session and the operative report, Nezhat described the cut as deliberate. He said he sliced the ureter to remove endometriosis that could have blocked urine flow.
Margolis was outraged. He said that he saw no endometriosis on the ureter and that the pathology report proved it.
''It was clear that Dr. Nezhat was performing an unnecessary procedure,'' he said in a sworn affidavit.
THE POLAN MEETING, 1996
More than two years passed before Stanford's quality assurance committee took up the review of the five cancer cases in which Spirtos had alleged improper surgeries by Camran Nezhat.
Just before the review committee was finally set to meet, Dr. Mary Lake Polan, chairman of obstetrics and gynecology, dropped by Margolis' office. He was one of the physicians reviewing the cases.
''We need to make sure that Nezhat is cleared on all these (cancer) cases,'' she told him, according to his affidavit.
Ultimately Margolis - and the other members of the quality assurance committee - voted in favor of Nezhat on all charges.
Polan said Margolis' allegations are false.
''I adamantly deny the statements attributed to me and deny there has been any pressure to exonerate any physician during the quality of care committee process," she declared in a written response to The Chronicle.
Margolis' decision to vote to exonerate Nezhat would haunt him for more than a year, until finally he had to act.
THE SHUER LETTER, 1998
In April 1998, Margolis met with Dr. Lawrence Shuer, chief of staff of the medical center. He told Shuer about the cut ureter incident and the pressure Polan had allegedly exerted on him.
''He (Shuer) acutely and abruptly ended our conversation, and I was excused from his office,'' Margolis said.
More than a year later, when Shuer learned Margolis was still criticizing the Nezhats and Stanford, he sent a written warning:
''Rest assured that Stanford Hospital and Clinics intends to pursue its full legal remedies if these defamatory and libelous statement do not cease,'' Shuer wrote.
Furious, Margolis, who had left Stanford to practice with Spirtos at the Women's Cancer Center in Palo Alto and Los Gatos, wrote back, saying that Shuer's job as chief of staff was ''patient protection not doctor protection.''
''The data which (the Nezhats) have published, including the rectal eversion procedure, is fraudulent, yet their publications are being accepted as standards in the surgical community. Stanford, by not auditing this clinical data, has ignored the concerns of scores of surgeons,'' Margolis wrote.
STANFORD'S DUTY, 2000
Defenders of the Nezhats at Stanford dismiss both Spirtos and Margolis as jealous competitors. But other medical experts say Stanford should have demanded a review of the 16 cases and has shirked its responsibility to verify the Nezhats' research claims.
''Stanford has a duty to review this,'' said Dr. Warren Grundfest, chairman of Biomedical Engineering at UCLA and an expert in new medical technologies. ''Serious allegations have been made by credible people, but Stanford has played like an ostrich with its head in the sand.''
But Stanford officials contend they are not obligated to review the 16 patient records because the rectal surgeries were performed in Georgia before the Nezhats came to the West Coast. Shuer said the procedure in question has never been performed at Stanford.
It was appropriate for the Nezhats to leave Mullen's case out of the medical journal, according to Stanford, because she was ultimately found not to have rectal endometriosis like the other patients.
Stanford reviewers have never asked the Nezhats or Northside Hospital for the records to verify the accuracy of the other 16 cases. ''We have no right to the records and do not want to violate patient privacy,'' said Stanford's lawyer Debra Zumwalt.
The university also never interviewed Mullen or the 20 doctors who have expressed concern over the Nezhats' research.
According to Stanford, the appropriate institutions to investigate the Nezhats are Northside Hospital, the Georgia Medical Board and Mercer University, where the Nezhats were clinical professors at the time of the surgeries. ''Stanford will carefully review the conclusions of those investigations,'' said Popp.
But a spokesman for Mercer, a Macon, Ga., medical school founded in 1986, said the school has no investigation pending.
The Georgia Medical Board's investigation of the Nezhats is continuing. The board will not comment on its status.
Stanford attorney Zumwalt said Margolis' complaint to Shuer regarding the cut ureter incident was never put in writing. Shuer said he asked Margolis for more information, and none was provided, but the case has now been identified and is being investigated by the quality assurance committee.
The university said the Nezhats have been cleared of allegations that they operated outside their specialty. Officials would not comment, however, on any details of the five quality assurance cases because they are confidential.
''One thing I can point out,'' said Zumwalt, ''is that doctors and patients and their families can reasonably disagree as to how aggressive to be in treating terminal diseases.''
GEORGIA COURTROOM, 2000
Mullen has refused to engage in monetary settlement talks with the Nezhats and promises to continue her suit until the records of the 16 other women are made public.
''My life has been changed in a very horrible and profound way by the experiment (that) Camran Nezhat has conducted upon me without my knowledge,'' Mullen said in an affidavit. ''I despair that other women will be injured by well-meaning surgeons who believe Camran Nezhat's article that there were no complications from this new surgery.''
In November, after a battle spanning six years - and six judges - Superior Court Judge Melvin Westmoreland in Atlanta ordered a confidential release of the records to Mullen's lawyers, and in January, the Nezhats and Northside Hospital turned them over.
While the records remain sealed, medical experts hired by Mullen's legal team to review the documents have written Judge Westmoreland expressing their concern about what the records contain, and urging that they be unsealed, in the public interest. ..
William Carlsen can be reached at wcarlsen@sfgate.com. Sabin Russell can be reached at sabin@sfgate.com.

Fact or Fiction?
DNA connects a mad scientist of today to one from the past!

In the movies, scientists are quite often "mad," and have been so since the silent movies.

The things they do, however, have been fairly consistent. They tend to be smarter than the “normal” human being, and wittier, often of a boastful nature. A surprising number can play Bach's Toccata and Fugue from memory. They will persevere despite repeated failures. These are usually on human subjects whose remnants, living or dead, are stored in commodious basements. Often unreliable technical equipment, anatomical parts and/or lab assistants plague these scientists.

What is it that we love about the mad scientists in our movies and history? Is it because their probing of the unknown piques our curiosity? Is it their seeming superiority to the common herd? Or is it that they -- at least for a while -- get away with more than we can?

They do so in many realms of knowledge. Some of them are practical, and quest for better things for the human race. Others are decidedly less practical. One of their most prominent technologies has been advanced medicine. Filmic mad scientists of the 1930s and 1940s led the vanguard in such efforts as keeping organs alive outside the body, cryogenics, new methods of surgery, robotic parts for humans, and new serums. Others harnessed electricity for all sorts of uses, but mostly to bring dead flesh back to life (always a useful ability), or to power advanced robots and death rays. It is the potential for cutting-edge science that makes fictions about the subject relevant.

These “mad scientists” are enthusiastic about their work, perhaps even carried away with it. They will let no one get in their way, especially those who call them insane, and start -- but do not finish -- going for the authorities. Generally their creations, be they mechanical or living, go out of control. Until the climax, that is, when they turn on their creator(s) and soon destroys them. This is usually due to “fate” or "God," which restores the status quo against the blaspheming mad scientist. And it is this last motif that connects the various aspects of the subject together: the "god-like" man who rejects the accepted ways and pursues the unknown, running into trouble as a result.

Few really believe in vampires, monsters and witches, but these enduring characters of Halloween have a basis in real life that is often more interesting than the fantasy.
Think of Halloween and your mind conjures images of ghosts, vampires, witches and monsters.

Our modern versions of them have largely been crafted by popular literature and, more influentially, the movies. But like many fantastic characters of myth and lore, they have a basis in reality.

Sometimes the true stories of these creatures that haunt our imaginations are just as weird and amazing as their fictional incarnations.

IHRT Presents for Your Halloween Entertainment
“The REAL Monsters of Halloween”

ENTER IF YOU DARE!






Castle Frankenstein –Darmstadt Bavaria Germany


The castle is perched atop a bluff of rock, a Gothic array of towers and pinnacles looming over the Rhine valley and once home to a troop of medieval knights. The hilly Oldenwald, which lies to the south of Darmstadt, is an area of little villages, rustic farms and Gothic churches.
The hilltops are crowned with thick forest while the valleys are framed with flower-studded meadows. The drive to Castle Frankenstein from Darmstadt station, takes 20 minutes.
First, you will cross the pancake-flat Rhine valley with its patchwork of asparagus and potato fields, then the road suddenly swings upwards and you are hurtle around a series of tight, vertiginous bends towards your destination. A 'Welcome to Castle Frankenstein,' sign greets you when your stomach-churning drive finally ends. The year, 2004!
You feel anxious as you near the huge doors that will take you into unknown areas of the castle, and as you enter, you see the first of two medieval towers built in the 16th century by Sir George Frankenstein. The towers are dimly lit by the fires of torches placed high in sconces set deep into the stone walls, walls that seem to reach forever skyward. As you continue to walk down the dusky, damp halls through the towers you realize that the foreboding halls of this impregnable fortress guarding the Rhine are consuming you and you start to think that you might never see the outside world again. Your fear heightens your every sense as you search shadowy crevices and gaze into the darkness with more anxiety then eager curiosity.
You smell terrible smells, hear terrible sounds, everything is so confusing, moving to fast to be real, your feeling weak, scared, and with each step you seem to be taken back in time; then you see it, a door, and it is opening, someone is coming toward you, it’s a man, a, a Dr. and he is dressed in period clothing from the 18th century!
This can’t be! All of a sudden your mind is filled with the thoughts of the experiments of the mad scientist, Italian physician Luigi Aldini, who in 1760 had injected a current of electricity into the head of a newly executed murderer, causing an array of horrible spasms, one of which opened the corpse's left eye! As this oddly dressed Dr. comes toward you, he is smiling as though you were a long lost relative. You do not recognize him, yet there IS something familiar about that smile, but what is? Your heart is racing with fear, your head swims and then…..your world goes black!

You wake in a sweat to find yourself strapped on a cold hard table in one of the castle's inner chambers, the same room in which a boy was born of refugee parents from Poland in 1673. In later life that boy turned man, would sign himself von Frankenstein in recognition of his birthplace. But he was never a nobleman, nor a blood relation of the Frankenstein family.
The dates, the years, the similarities of then and now are all merged into one blur in your mind as you are wheeled into a modern operating room in a foreign country.
Eyes that look like yours are everywhere, eyes behind masks, eyes everywhere looking at you, then voices, lots of words but in a language you don’t understand. The Dr., that smile, it is one and the same, how can that be in this modern age, but you will get no answer to that question, as once again your world goes black, and the experiments begin!










Johann Konrad Dippel (1673-1734)

The Frankenstein Monster
Our story starts out with the birth of an 18th century mad scientist who was born in 1673 in Germany at - believe it or not - Castle Frankenstein! Johann Konrad Dippel (1673-1734) was born to immigrants to Germany, and has no “blood” relationship to the Frankenstein’s of Noble German decent!
Dipple, a man of great pride, felt no limitations to his intellect and was interested in pursuing the great mysteries of life. When he registered at the University of Giessen (sixty miles north of the real Castle Frankenstein near Darmstadt, Germany), he registered as "Franckensteina." Some three years later he completed his dissertation. As it was a skeptical work -- whose title De Nihilo meant "On Nothing" -- it outraged many of his superiors. Dipple flaunted that he was smarter than the “normal” human being, and wittier, and was often of a boastful nature, and with an attitude that gave one the impression he could care less what others thought of him!
Educated as a physician, Dippel set up a laboratory at Castle Frankenstein where he would be free to conduct his bizarre experiments. There's no record of whether or not he had a hunchbacked assistant named Igor, but Dippel (who often went by the name Konrad Frankensteina) spent a lot of his time with his hobby of alchemy - a popular pursuit of the day. Alchemy(1) is a kind pseudoscientific experimentation with the elements - crazy chemistry - whose ultimate challenge was to be able to turn lead into gold. Dippel was also fascinated by the possibility of immortality through scientific means.
Though a brilliant scientist, Dipple got caught up in the dark world of alchemy and body snatching. He really did use the parts of butchered animals and exhumed human corpses in his vain attempt to "engender life in the dead," in his own words. He claimed to have the secret of the “philosopher's stone,”(2) as well as the ability to create life.
Unlike his literary and cinematic "decedents," Dippel did not rig up the body parts to elaborate lightning-powered gizmos and spark generators. Rather he boiled everything - skin, muscle, bone, blood, hair and organs - in large vats. When the surrounding community got wind of what Dippel was up to, maybe they didn't storm his castle with torches, shovels and rakes, but they did kick him out of town.
Dipple returned to Guessen hoping for a fellowship there, but meeting with a cold reception there, he went to Wittenberg, where his fortunes proved no better. At Strasburg, his views made it impossible for him to establish any connection with that university, but he did do some lecturing on astronomy and palmistry, preaching frequently in a spirit that soon led him to be dismissed. Dipple had developed a lifestyle
That ultimately forced him back to his native place, a fugative from his collectors!
Finding a new faith, Dipple entered into it with a fierce pace that led him to fame. In less then two years he 14 controversial writings on the theme of morals verses dogma, among other subjects, and like everything else he ever did, he went to extremes, which subjected him to persecution from the clergy and even from the mob, by whom his life was threatened.
By 1704 Dipple had moved to Berlin and devoted his researches to alchemy and deluded at one time that he had solved the problem of transmutation! He was driven out of Berlin and fled to Kostrits, thence moved on to Holland, where he lived for some time near Amsterdam. In 1711 he practiced medicine in Leyden, and wrote a number of papers on theology and in 1714 had his papers published. In this same year he relocated to Altona, in Sleswick-Holstein where an imprudent incursion into politics aroused the hatred of high officials, and in 1719 he was condemned to perpetual imprisonment. Though the full sentence was never carried out, Dipple did live for 7 years in semi-confinement on the island of Bornholm. Released in 1726, he went to Sweden where he became the physician to King Frederick I. Once again he aroused the clergy there and was banished from the country.
Returning to Germany, he took up residence in Liebenberg, near Goslar, and
Continued his studies in alchemy. Though he abstained entirely from theological controversy, the clergy compelled him to flee, and he found refuge with the Count of Wittgenstein-Berleburg. His last years were largely taken up by violent controversy with Zinzendorf over the nature of the Atomement.
Once again, fleeing persecution, Dipple returned to “Frankenstein Castle” in Bavaria, Germany where rumors circulated that he was again collecting body parts to assist in the making of a formula that Dipple claimed would allow him to live to the age of 135. On the morning of April 24th, 1734, Dipple’s body was found in his laboratory by one of his friends. It is believed that he died by drinking his own potion.

After a tumultuous and lonely life, Johann Konrad Dippel became another legend in the history of Frankenstein, though he would never be recognized for his scientific abilities, instead he became known as "Dipple the Alchemist".


They say that all the spirits of those who were experimented on during Dipple’s time haunt the “Frankenstein Castle” yet today, but the haunting does not stop there. A “ NEW” kind of “haunting” out of the “Frankenstein Castle” reveled itself over 233 years later in the birth of another boy born to parents of Polish decent! A direct descendent of the late Johann Konrad Dippel, this boys life will bear an astonishing similarities to that of his infamous relative!!

Revealing the true life experiments of
"Dr. Dipple Hook" aka "Dr. Daniel Kruschisnki"






















Daniel Marion Konrad Kruczinsky (1958 - Present)

Madness At The Edge Of Science
Daniel Kruczinsky was born in 1958 in Poland. In 1969 he moved with his family to Munich Germany after his father was released from the Auschwitz concentration camp in Poland. His upbringing was tumultuous and lonely as he strived to live up to his father’s expectations, unrealistic expectations that no human being could ever really live up to. Daniel’s boyhood days would be filled with a cold harshness that could only have come out of someone who spent years in a concentration camp, and years where every human emotion was drained from the very core of the prisoner’s body.
With his life missing the essentials necessary for a child to grow strong in self esteem and character, Daniel soon found himself empty of both and not feeling any self worth or value to anyone, he became soon became void of emotions as well.
Early in his youth he started to “create” identities that he thought would give him the recognition and love he always craved, but never received growing up. Though he had a mother, it was the love, attention and respect from his father that he craved throughout his childhood, thus his mother became a non-entity in his life, and continues to be that yet today. Daniel not only created multiple identities, he perfected lies about himself to the point that he became what is known today as a, “pathological liar” in which the liar actually starts to believe their own lies, not being able to tell truth from fiction.
As he moved out into the world, Daniel Kruschinski changed the Polish spelling of his name hoping that he would be better accepted by his peers, and possibly out of feelings that he was not worthy to carry that name having failed receiving respect and love from his father.
He began his medical studies at Düsseldorf University in October 1979, and finished in November 1985. For the dissertation entitled "Selective histochemical zinc presentation in testis of the Wistar rat", carried out at the Anatomical Institute of Düsseldorf University under Prof. H.G. Goslar, he was awarded his doctorate in September 1986 with the mark "Summa cum laude". As his dissertation was a skeptical piece of work, many of his superiors were not surprised as throughout his time at the university, Daniel was seen as being rather, freaky.” Kruschinski flaunted that he was smarter than the “normal” human being, and wittier, and was often of a boastful nature, and with an attitude that gave one the impression he could care less what others thought of him!
In what seemed to be a hasty change of mind from a future in the area of research, Kruschinski turned his education to the area of gynecology and obstetrics at the gynecology clinic of the Franzkiskus-Hospital in Bielefeld under the direction of Prof. Dr. med. J.D. Schnell and continued at the gynecology clinic of Minden Hospital under Prof. Dr. med. H. Wagner. Educated as a physician now, Kruschinski set up practices in private centers where he would be free to conduct his bizarre experiments. There's no record of whether or not he had a hunchbacked assistant named Igor, but “Doc. Kru” (who often went by that name on his Internet message boards) did have an assistant who he said was a nurse, but in reality, she was only his mistress, never having been trained as a nurse, yet working side by side with him in his operating room during these experimental procedures!
From 1990 to 1995, Dr. Kruschinski worked at the Clinic and Polyclinic for Obstetrics of Johannes Gutenberg University Mainz under Prof. Dr. med. P.G. Knapstein. Here he established the center for minimally invasive surgery and was in charge of consulting hours for plastic surgery of the breast. After this, Dr. Kruschinski was attending physician at the University Gynecology Clinic at the Knappschaftskrankenhaus Bochum-Langendreer under Prof. Dr. med. A. Jensen. And then in February 1998 he established a surgical office in Alzey, focusing mainly on minimally invasive surgery. Following consultation here, he treated his patients in the Kirchheimbolanden Hospital. Finally, on admission as faculty member to the faculty of medicine of the private Witten / Herdecke University he was made head of the Institute for Endoscopic Gynecology. Little did he know that he would continue to “run” from Klinik to Klinik, and move between some of the same cities that his relative, Johann Konrad Dippel had done for so many years, and for the same reasons as his ancestor had! To name a FEW: Schärding-Austria, Offenbach, Eilenriedeklinik Hannover, Klinik am Zuckerberg Braunschweigm, Emma Klinik, Seligenstadt, Passua, Rotthalmünster, Bavaria, Bochum-Langendreer, Mainz, Bielefeld, WittenGermany!






Dr. Kruschinski went on to create a world that he was certain would evolve into his wildest dreams, one of fame, fortune and world domination! He created, “EndoGyn® - Institute for Endoscopic Gynecology,” and that move would lead him into the dark world of human experiments, extremes in surgeries, obsessions with surgical techniques, surgical instruments and procedures, pushing things to the limits and beyond. Not seeming to care who got hurt by his extremes, he continued to harvest patients to his operating rooms with lies, deceit, and “charisma!”
His whole life would be filled with short -lived relationships! His peers would continue to find him, “freaky” and “odd” to be around. He started to drink heavy, remaining in his offices day and night! He would write controversial paper’s, which only served to anger those in the scientific world of research, as he wrote them without any proof of validating research associated with them. Time and again, his scientific writings would be proven false in content!
As in keeping with the times, Dr. Kruschinski used the Internet as a means to make himself known, and unfortunately, to make his fortune! For a brief time it seemed as though he would accomplish his dream of becoming a famous International surgeon, a “savior” of sorts. He would even publicly compare himself to “Einstein,” and to “God!” “Doctors from EndoGyn® are now performing surgery in many locations and hospitals. The idea of franchising endoscopic surgery is getting reality” he would say over and over again, seeming only to be fooling him-self!
Dr. Kruschinski made lots of money from performing operations on people from all over the world, people who had to pay him cash if they wanted HIS special 100% proven surgery that he promised would cure them! And pay they did, for a while that is!
Soon these patients were NOT getting well, and many of them were returning to his operating room time and again, and paying cash each time! Some of these patients were almost cut in half in operations were he called himself a “reconstructive surgeon,” yet not ever having had that training! Others were placed on a “hook” that suspended them into the air like beef hanging in the slaughterhouse! Time and again he overused this “hook” apparatus, causing severe damage to those he used it on, and left many of them in horrible, non-reversible pain and disabling symptoms!
“Doc. Kru” even gave discounts to some if they would keep the secret that he did not make them well, let alone cure them! And some patients did this so they could come back and let him try again to heal them, only to find themselves once again on the “hook!”
It soon it became apparent to him that he could no longer “scam” patients over the Internet, and he lost money, causing him to fall into bankruptcy, losing his hospital affiliations time and again, and soon he found himself a fugitive from his collectors! What he did seem to accomplish through his use of the Internet was the cult like followers who, no matter if he had injured them in a surgery, insulted them in a public manner by calling them drug addicts and alcoholics, they continue to praise him! They praise him even after he confessed that he did in fact perform experiments on his patients and then boldly published a paper on it!
Dr. Kruschinski was so void of ethics and morals, that he would deny his Jewish birth when it benefited him, then used it when it benefited him, and at times, he even professed to be a Catholic in order to be “accepted” into a community of Christians at a Klinik he was hoping to infiltrate!
Though Dr. Daniel Kruschniski has lost everything that would associate him to being a Dr., and fleeing from one area of Germany to the other, at ties calling upon patients and colleges to let him sleep in their homes, he lives on, surfacing now and then on the Internet! It is apparent that “Doc. Kru” has reverted back to the original opinion of himself, which is an empty shell of a human being, he uses posts on the Internet as if he is gasping for a breath, as it will only come in the words of praise from those who are as dysfunctional as he is, yet, this IS all that is left of his life.
Soon his Internet web site will shut down, moneys due it not forthcoming and Endogyn will be gone, and as “Doc Kru” said in his own words, “I am Endogyn, and Endogyn is me. Where it is, I am, and so be it!” As he desperately posts his last words, and there is no way to send them across the Internet, he will breath his last breath before he slides into the murky, darkness of his ways. He will cease to exist! Because of his upbringing, he saw himself as a failure, an empty shell, a “nothing” and in this, he was finally right!

Kru will drown from an emotion he wasn’t even aware that he had. No, it is not guilt of what he did to others, as he is void of that emotion, but from his own inability to be able to be someone he created, and even in that, he failed!

Though unlike his ancestor, Johann Konrad Dippel, Daniel Kruschinski “lives” but he lives as a “nothing.” Dr. Daniel Kruschinski, like his ancestor, Johann Konrad Dippel, after a tumultuous and lonely life, became another legend in the history of Frankenstein, though he too would never be recognized for his scientific abilities, instead he has became known as "Kruschinsky the Phsycho-Surgeon" who experimented on his unsuspecting patients from 2003-2006 and admitted it to the world!”

Where will he surface next? Where YOU one of his victims?
Do YOU know who is performing YOUR surgery?

"Happy Halloween"



(1) “Alchemy” hovered between worlds. It emerged in a time-between-times, after a Dark Age had brightened but before a Renaissance had dawned. It came from Arab and Greek sources, but it flourished in theWest. It lay between faith and philosophy; it still dreamed of heaven, but it focused on the Earth.

(2) The “Philosopher's Stone,” in Latin lapis philosophorum, is a mythical substance that supposedly could turn inexpensive metals into gold and/or create an elixir that would make humans younger, thus delaying death.

FDA:Potential Signals of Serious Risks/New Safety Information Identified by the Adverse Event Reporting System (AERS)

January - March 2008

The table below lists the names of products and potential signals of serious risks/new safety information that were identified for these products during the period January - March 2008 in the AERS database. The appearance of a drug on this list does not mean that FDA has concluded that the drug has the listed risk. It means that FDA has identified a potential safety issue, but does not mean that FDA has identified a causal relationship between the drug and the listed risk. If after further evaluation the FDA determines that the drug is associated with the risk, it may take a variety of actions including requiring changes to the labeling of the drug, requiring development of a Risk Evaluation and Mitigation Strategy (REMS), or gathering additional data to better characterize the risk.
FDA wants to emphasize that the listing of a drug and a potential safety issue on this Web site does not mean that FDA is suggesting prescribers should not prescribe the drug or that patients taking the drug should stop taking the medication. Patients who have questions about their use of the identified drug should contact their health care provider. FDA will complete its evaluation of each potential signal/new safety information and issue additional public communications as appropriate.

Potential Signals of Serious Risks/New Safety Information Identified by the Adverse Event Reporting System (AERS) January - March 2008

Product Name: Active Ingredient (Trade)or Product Class
Potential Signal of Serious Risk/New Safety Information

Arginine Hydrochloride Injection (R-Gene 10)
Pediatric overdose due to labeling / packaging confusion

Desflurane (Suprane)
Cardiac arrest

Duloxetine (Cymbalta)
Urinary retention

Etravirine (Intelence)
Hemarthrosis

Fluorouracil Cream (Carac) and Ketoconazole Cream (Kuric)
Adverse events due to name confusion

Heparin
Anaphylactic-type reactions

Icodextrin (Extraneal)
Hypoglycemia

Insulin U-500 (Humulin R)
Dosing confusion

Ivermectin (Stromectol) and Warfarin
Drug interaction

Lapatinib (Tykerb)
Hepatotoxicity

Lenalidomide (Revlimid)
Stevens Johnson Syndrome

Natalizumab (Tysabri)
Skin melanomas

Nitroglycerin (Nitrostat)
Overdose due to labeling confusion

Octreotide Acetate Depot (Sandostatin LAR)
Ileus

Oxycodone Hydrochloride Controlled-Release (Oxycontin)
Drug misuse, abuse and overdose

Perflutren Lipid Microsphere (Definity)
Cardiopulmonary reactions

Phenytoin Injection (Dilantin)
Purple Glove Syndrome

Quetiapine (Seroquel)
Overdose due to sample pack labeling confusion

Telbivudine (Tyzeka)
Peripheral neuropathy

Tumor Necrosis Factor (TNF) Blockers
Cancers in children and young adults

http://www.fda.gov/cder/aers/potential_signals/potential_signals_2008Q1.htm