Study outlines optimal therapy for breast cancer with BRCA mutation

Those are the findings of a 10-year study led by researchers at the University of Michigan Comprehensive Cancer Center. The study authors found that women with the genetic mutation who had their ovaries removed or took the anti-estrogen drug tamoxifen had lower rates of breast cancer recurrence or new breast cancers in the other breast.

Women who carry a mutation on the BRCA1 or BRCA2 gene are at an increased risk of breast cancer compared to women without the mutation. And once diagnosed with breast cancer, they face a higher rate of a second tumor occurring. Because of this, questions remain about whether these women should undergo breast-conserving surgery instead of mastectomy, which removes the entire breast.

In this study, published in the June 1 issue of the Journal of Clinical Oncology, researchers from 11 centers looked at 160 women with early breast cancer and the BRCA1 or BRCA2 gene mutations. The women were treated with lumpectomy, surgery to remove only the tumor, followed by radiation therapy. These women were compared to 445 similar women who were treated for breast cancer but did not carry the genetic mutations.

After 15 years, both groups of women had similar rates of the tumor reoccurring in the same breast. But among the women with the BRCA1 or BRCA2 mutations, those who were further treated by having their ovaries removed, a procedure called oophorectomy, were less likely to have a recurrence. Similarly, tamoxifen dropped the risk of same-breast recurrence for the mutation carriers by 58 percent.

Women with the genetic mutations had a significantly greater risk of developing breast cancer in the opposite breast than did the control group. After 15 years, 45 percent of the women with the mutation who had not undergone oopherectomy developed a second breast cancer in the other breast, compared to only 9 percent of those women without the genetic mutation.

Women with the mutation who took tamoxifen had a 69 percent reduction in breast cancer in the opposite breast. Among women who did not undergo oophorectomy, tamoxifen made a significant difference: 6 percent of those taking tamoxifen had a second cancer in the opposite breast after 15 years, compared to 54 percent of those who did not take tamoxifen.

�For women with early stage breast cancer who are BRCA1 or BRCA2 carriers, our 10-year data suggest that oophorectomy or tamoxifen in women treated with breast conservation and radiation therapy help to reduce the risk of recurrences and new primary cancers in the treated breast to levels comparable to those observed in women with early stage breast cancer who are not BRCA1 or BRCA2 carriers,� says lead study author Lori J. Pierce, M.D., professor of radiation oncology at the U-M Medical School.

Lifestyle, diet may stop or reverse prostate cancer progression

The research is the first randomized, controlled trial showing that lifestyle changes may affect the progression of any type of cancer. Study findings are published in the September issue of the Journal of Urology.

The study was directed by Dean Ornish, MD, clinical professor, and Peter Carroll, MD, chair of the Department of Urology, both of the University of California, San Francisco, and the late William Fair, MD, chief of urologic surgery and chair of urologic oncology, Memorial Sloan-Kettering Cancer Center.

The research team studied 93 men with biopsy-proven prostate cancer who had elected not to undergo conventional treatment for reasons unrelated to this study. The participants were randomly divided into either a group who were asked to make comprehensive changes in diet and lifestyle or a comparison group who were not asked to do so.

After one year, the researchers found that PSA levels (a protein marker for prostate cancer) decreased in men in the group who made comprehensive lifestyle changes but increased in the comparison group. There was a direct correlation between the degree of lifestyle change and the changes in PSA. Also, they found that serum from the participants inhibited prostate tumor growth in vitro by 70 percent in the lifestyle-change group but only 9 percent in the comparison group. Again, there was a direct correlation between the degree of lifestyle change and the inhibition of prostate tumor growth.

Bladder problems increase in men as they age, study reports

Their findings remind patients and their physicians that urination difficulties in men can be better cared for at early onset. Additionally, the study notes that as men age, the possibility increases that they will experience problems with urination.

"What we know is that many men ignore their symptoms and do not seek assistance with their physician until much later," said Andrew Rule, M.D., nephrologist and epidemiologist at Mayo Clinic and the lead author of the study. "What happens is men can end up with a bladder not working, perhaps needing a bladder catheter all the time. They also become at increased risk for bladder infections and even kidney failure problems."

The researchers looked at information in men from two tests: post-void residual and voided volume. The post-void residual test involved men urinating and then having an ultrasound scan to determine how much urine remained in the bladder. The voided volume test measured how much urine men could void with a full bladder.

Dr. Rule said that both tests are difficult to interpret in a patient because they can yield varying results with the same person each time. However, because the study relied on hundreds of men with multiple visits, those variations could be lessened. The study looked at a random sample of 529 men, ages 40 to 79, who were followed with the two tests every two years for up to 12 years.

Dr. Rule says the study presents some new data on the natural history of the post-void residual and void volume in men as they age.

Shock wave therapy for kidney stones linked to diabetes, hypertension

Risk for diabetes was related to the intensity of the treatment and quantity of the shock waves administered; hypertension was related to treatment of stones in both kidneys.

Shock wave lithotripsy uses shock waves to break up an impassable kidney stone into smaller, sandlike pieces which can be passed spontaneously, usually within a month. The patient and the lithotriptor that emits the shock waves are placed in a water bath. Water allows easier conduction of the shock waves through the patient's tissue and precise focus on the kidney stone.

"This is a completely new finding," says Amy Krambeck, M.D., Mayo Clinic urology resident and lead study investigator. "This opens the eyes of the world of urology to the fact that hypertension and diabetes are potential side effects. We can't say with 100 percent certainty that the shock wave treatment for the kidney stones caused diabetes and hypertension, but the association was very strong. The risk of developing diabetes after shock wave lithotripsy is almost four times the risk of people with kidney stones treated with medicine, and the risk of developing hypertension is one and one-half times, which is a significant risk increase."

The study, which is the first examination of the effects of shock wave lithotripsy over the long term, involved reviewing charts of 630 patients treated with shock wave lithotripsy in 1985 at Mayo Clinic. The researchers sent those still alive a questionnaire; almost 60 percent responded. The researchers matched the patients treated with lithotripsy to patients similar in age, gender and initial time of seeing a urologist for kidney stones who received a different treatment, medicine. Nineteen years post-treatment, those treated with lithotripsy had 3.75 times the risk of having diabetes as those given the other kidney stone treatment. The degree of increased risk rose with greater number and intensity of shocks administered. Those treated with lithotripsy also had 1.47 times the risk of having hypertension -- high blood pressure -- than those who received the other kidney stone treatment; risk was highest for those who had both kidneys treated.

Scalpel-free surgery could reduce risk of HIV and hepatitis

"While these rates are alarming, they are not entirely unexpected. General precautions have been in effect for some time to prevent the spread of disease to health care workers in the operating room," said Martin A. Makary, M.D., assistant professor of surgery and public health at Johns Hopkins and lead author of a report in the May 2005 issue of the Annals of Surgery.

"Given the high incidence of these infections, however, we have developed new strategies such as 'sharpless' surgery-a surgical technique which uses high-technology alternatives to needles and knives. We advocate using these techniques whenever possible in high-risk settings to further protect health care workers from accidental transmission," added Makary.

Sharpless surgical techniques include laparoscopy, electrocautery to replace scalpel incisions, and skin clips or glue instead of sewing to close or repair wounds.

Previous studies have shown that health care workers are injured in about 7 percent of operations. As many as 87 percent of surgeons will receive an injury that breaks the skin -- thus allowing for possible disease transmission - at some point in their career. There are an estimated 40,000 new cases of HIV each year, and hepatitis C is increasing at an even faster rate, according to the report. The study concludes that by studying the rates of HIV and hepatitis B and C among patients presenting for surgery, a more accurate incidence of disease is measured within a community, bypassing the selection bias of traditional statistics of known infected patients presenting to primary care clinics. Furthermore, the authors report that blood-borne pathogens are associated with certain types of operations.

The researchers also found that the operations associated with the greatest risk of infection - lymph-node biopsy, soft-tissue-mass excision and abscess-drainage cases - were often assigned to the most inexperienced surgeons-in-training, placing them at greatest risk.

"Sharpless surgical techniques combined with traditional precautions and early education for surgery trainees are the most practical ways to reduce the risk of infection to health care workers," said Makary.

The researchers studied 709 consecutive adult general surgery operations performed between July 2003 and June 2004 in the community surgical service at The Johns Hopkins Hospital including inpatient, emergency department and outpatient surgical procedures. Data were collected on HIV, hepatitis B and hepatitis C test results, type of operation, age, sex and history of intravenous drug use.

The researchers found that 38 percent of all operations involved a bloodborne pathogen, and almost half (47 percent) of all men tested positive for at least one infection. HIV accounted for 26 percent of infections, hepatitis B for 4 percent, hepatitis C for 35 percent, and co-infection with HIV and hepatitis C accounted for 17 percent of infections. In addition, bloodborne pathogen infection was found in up to 65 percent of patients with a history of intravenous drug use and in as many as 71 percent of patients undergoing a soft-tissue abscess procedure or lymph-node biopsy.

While the patients in this study tend toward low socioeconomic status and increased substance use, most university hospitals in the United States are located in urban areas and serve a similar patient population, added Makary.

Other authors on the report are Eric S. Weiss, Theresa Wang, Dora Syin, Peter Pronovost, David Chang and Edward Cornwell III.

Surgery found to be best remedy for hammer hand

"In the past, treatment of hypothenar hammer syndrome has been controversial, and physicians have been searching for some way to treat it," says Craig Johnson, M.D., chair of Mayo Clinic's Division of Plastic Surgery and lead study investigator. "From our study, it's clear that people with this syndrome shouldn't be treated with medication or other treatments, but with surgery."

Dr. Johnson explains that symptoms improved in 78 percent of the patients in his study who underwent a bypass grafting operation and that he witnesses an almost immediate relief in his patients with this surgery.

"Post-surgery, patients feel their hands are warmer right away, though ulcers take a little longer to heal," he says. "Most people do quite well and get back to work quickly."

Patients with this condition have a damaged ulnar artery, a key means of blood flow to the hand. In addition to the sensory damage, they also can develop small ulcers in their fingertips resulting in blackened fingers or even gangrene, due to lack of oxygenation.

"Many times they can't do their jobs due to pain," says Dr. Johnson. "They have cold intolerance, so often they can't go outside when it's cold or handle anything chilled, like cold meat. They also can't hold heavy objects."

The treatment found to improve these symptoms, bypass grafting surgery, involves removing the damaged portion of the artery, which Dr. Johnson describes as clotted much like a clogged lead pipe. The artery's blood flow is then restored by replacing the section of blocked artery with a vein graft.

In this study, Dr. Johnson studied 115 hands in 101 patients evaluated at Mayo Clinic. Medical and surgical treatment options pursued were evaluated by chart review and postoperative phone calls for all patients, and by duplex scan, an ultrasound of the arteries that measures blood flow, for those who underwent bypass surgery. The patients studied included 98 males and three females; most were laborers.

An average of 3.5 years post-treatment, 29 of the 41 patients treated with medication or sympathectomy -- surgery to interrupt the nerve pathway -- showed no change in symptoms, seven were worse and five showed symptom improvement.

Two types of excision operations were used for the remaining 60 patients studied. Four received excision of the damaged portion of the ulnar artery or surrounding vessels followed by ligation, or binding; symptoms in three out of four of these patients were unchanged post-surgery. The other 56 patients were treated with surgical excision of the damaged ulnar artery or surrounding vessels followed by bypass grafting; 78 percent of these patients improved, losing their pain and cold intolerance and returning to work. Of the 22 percent who showed no change or worsening of symptoms following bypass grafting surgery, 86 percent of the patients had continued smoking.

Dr. Johnson explains that quitting smoking is key to a lasting effect of the bypass grafting surgery, thus he tries not to operate on patients who continue to smoke. "Smokers do well for awhile, but over time their bypass graft gets clotted," he explains.

The cause of hypothenar hammer syndrome is unknown. Previously the condition has been thought to be task or work related due to use of the palm as a hammer, but this is yet unsettled, says Dr. Johnson. "It's not entirely certain whether you have to be running a jackhammer for 20 years or laying concrete to develop this syndrome." There could also be a genetic predisposition to the syndrome, he indicates. Dr. Johnson points to a need for further research into the origins of this syndrome.

Obesity surgery translates to cardiac benefit

In a study presented at the American College of Cardiology's 55th Annual Scientific Session, a team of researchers from the Mayo Clinic in Minnesota evaluated the effect of bariatric surgery on longterm cardiovascular risk and estimated prevented outcomes. ACC.06 is the premier cardiovascular medical meeting, bringing together over 30,000 cardiologists to further breakthroughs in cardiovascular medicine.

The team completed a historical study between 1990 and 2003 of 197 patients with class II-III obesity who undertook Roux-en-Y gastric bypass surgery (sometimes referred to as "stomach stapling"), compared to 163 control patients enrolled in a weight reduction program. With an average follow-up time of 3.3 years, the team recorded changes in cardiovascular risk factors such as cholesterol levels, body mass index (BMI) and diabetes criteria.

Though the team originally estimated a higher 10-year risk for cardiac events in the surgical group at the start of the study due to their associated conditions, researchers found at follow-up that the patients had a much lower risk than the control group for having a heart complication (18.3 vs. 30 percent). Using the study parameters and risk models based on previously published data, the team estimated that for every 100 patients, the surgery would prevent 16.2 cardiovascular events and 4.1 overall deaths, as compared to the control group. However, should the number of deaths during surgery approach 4 percent, the protective effect is limited, as may be in the case in centers with very low volumes of weight loss surgeries.