Cancer

CRM197 enhances antitumor effect of paclitaxel in ovarian cancer

2009-04-03T22:41:00.003-07:00

CRM197, an inhibitor of heparin-binding EGF-like factor (HB-EGF), is synergistic with paclitaxel against ovarian cancer, according to a report in the March 15th issue of the International Journal of Cancer.HB-EGF appears to play a critical role in ovarian cancer cell growth and tumor progression, the authors explain. CRM197 binds to HB-EGF and blocks its mitogenic activity by preventing it from binding to EGFR. Dr. Shingo Miyamoto from Fukuoka University, Japan, and colleagues investigated the antitumor effects of paclitaxel and CRM197 in ovarian cancer cell culture and in nude mice injected subcutaneously with ovarian cancer cells. Paclitaxel induced transient ERK activation and sustained activation of JNK and p38 MAPK, effects that were reduced by overexpression of HB-EGF, the authors report. CRM197 effectively suppressed the paclitaxel-induced anti-apoptotic signals mediated by ERK and Akt, and enhanced the pro-apoptotic signals JNK and p38 MAPK. In nude mice with ovarian cancer xenografts, the researchers note, paclitaxel and CRM197 synergistically inhibited tumor formation, completely blocking tumor formation at doses of 10 mg/kg paclitaxel and 5 mg/kg CRM197. "In this study," the authors conclude, "the enhancement of HB-EGF expression abrogates the antitumor effect of paclitaxel by altering the balance of anti-apoptotic and pro-apoptotic signals induced by paclitaxel. The treatment of CRM197 in conjunction with paclitaxel results in a marked synergistic antitumor effect in ovarian cancer cells in vivo, suggesting a novel combination therapy for ovarian cancer patients including those showing chemo-resistance." "Phase 1 study of the use of CRM197 has already started for patients with advanced ovarian cancer in Fukuoka University under the approval of the ethical committee," the investigators add.

CRM197 enhances antitumor effect of paclitaxel in ovarian cancer

2009-04-03T22:41:00.001-07:00

Triple-negative breast cancer more common in blacks, regardless of age, weight

2009-04-03T22:40:00.001-07:00

Black women have a threefold greater risk of developing triple-negative breast cancer (negative for estrogen receptor, progesterone receptor, and HER-2) compared to non-black women, regardless of age or body weight, Boston-based researchers report. "The higher prevalence of triple-negative breast tumors in black women in all age and weight categories likely contributes to black women's unfavorable breast cancer prognosis," Dr. Carol Rosenberg from Boston University School of Medicine noted in comments to Reuters Health. "The reasons explaining this finding are not certain, but it is possible that black women may be at intrinsically greater risk of these more aggressive tumors," she added. Dr. Rosenberg and colleagues looked at the clinical and pathologic features of breast cancers in a diverse group of 415 women. Thirty-six percent of the women were white, 43% were black, 10% Hispanic and 11% of "other" races. Forty-seven percent of the women were obese. Most of the breast tumors (72%) were estrogen receptor-positive and/or progesterone receptor-positive; 20% were triple-negative and 13% were HER2-positive. The investigators focused on triple-negative tumors, which are associated with poor prognosis, and found that the odds ratio for having this tumour type was 3.0 for black women compared with white women. Triple-negative tumors made up equal fractions -- roughly 30% -- of breast cancers in younger and older black women and in obese and non-obese black women, according to the team's report published online March 25 in the journal Breast Cancer Research. "It was known previously," Dr. Rosenberg commented, "that premenopausal black women had more triple-negative tumors. However, there were no previous data about weight. What we found that was new was that these tumors were just as common in black women diagnosed before or after age 50, and in those who were or were not obese." The investigators conclude, "Other factors must determine tumor subtype."

Gemcitabine-cisplatin could be clinically useful in metastatic breast cancer

2009-04-03T22:39:00.002-07:00

The combination of gemcitabine and cisplatin is active against metastatic breast cancer, whether prior treatment has been minimal or aggressive, according to two phase 2 studies published online on March 23 by the Journal of Clinical Oncology. The parallel studies, designed by the California Cancer Consortium and Loyola University Chicago and led by Dr. Helen K. Chew at the University of California Davis, Sacramento, enrolled 136 patients with histologically confirmed metastatic or locally recurrent breast cancer. Their median age was 46 years. One of the two study populations comprised 74 women who had been heavily pretreated, with at least two chemotherapy regimens for metastatic disease or disease progression after bone marrow or hematopoietic cell transplantation. In addition, all had received anthracycline or taxane therapy. The 62 women in the minimally treated population had received no more than one prior regimen, without either cisplatin or gemcitabine. Treatment during the study was a 21-day cycle with cisplatin 25 mg/m² daily on days 1 through 4 and gemcitabine 1,000 mg/m² on days 2 and 8. Participants in the heavily pretreated group received a median of three cycles of protocol therapy, while those in the minimally pretreated group received a median of four. The overall response rate was 26% in both groups. The duration of response was 5.3 months in the heavily pretreated group and 5.9 months in the minimally pretreated. Median overall survival was 10.8 months in the heavily pretreated group and 13.1 months in the minimally pretreated. In a subset of 55 patients, the study also analyzed polymorphisms in 10 genes relevant to gemcitabine and cisplatin, including those involved in DNA repair, drug metabolism and cell-cycle control. The XPD-751 polymorphism was associated with significantly increased overall survival, among participants who carried the Lys allele rather than the Gln allele. The XRCC3 polymorphism was associated with significantly better response rate and progression-free survival among patients who carried the Thr/Thr genotype instead of the heterozygous Met/Thr genotype."Our findings," the researchers write, "implicate the potential importance of DNA repair enzymes and drug metabolism enzymes in the prediction of clinical outcome to chemotherapy in metastatic breast cancer."

Fecal occult blood screening may help reduce colorectal cancer mortality

2009-04-03T22:39:00.001-07:00

Pilot studies indicate that a population-based approach to guaiac fecal occult blood testing (FOBT) appears likely to reduce colorectal cancer mortality, Scottish researchers report in the April issue of Gut."This study," lead investigator Dr. Robert J. C. Steele told Reuters Health, "clearly demonstrates that a national screening program for bowel cancer using fecal occult blood testing has the potential to reduce death rates from this disease by between 15% and 20%.""As a result of this study," he added, "the Scottish Government Health Department has committed to rolling out a national screening program, which should be complete by the end of 2009. A similar activity is taking place in the rest of the United Kingdom."Dr. Steele of Ninewells Hospital & Medical School, Dundee and colleagues conducted the screenings in the Grampian, Tayside and Fife areas of the country. More than 300,000 subjects participated. Overall, the uptake -- the proportion of those invited who actually attended -- was about 55%.In the first round, the positivity rate was 2.07% and the cancer detection rate was 2.1 per 1000. For the second round, corresponding values were 1.9% and 1.2 per 1000. In the third and final round, they were 1.16% and 0.7 per 1000.Over the 3 rounds, positive predictive values for cancer were 12%, 7% and 7.5%, and for adenoma, they were 36.5%, 30.3% and 29.1%. The corresponding percentages detected at Duke's stage A were 49.2, 40.1 and 36.3.Despite the apparent promise of the approach, concluded Dr. Steele, "it has to be emphasized that success of these programs is crucially dependent on uptake, and future efforts must focus on engaging the British population in this activity."

Steroids pose low risk of adrenal insufficiency after infantile hemangioma therapy

2009-04-03T22:38:00.001-07:00

The prevalence of adrenal insufficiency following systemic glucocorticoid therapy does not appear to be at significantly increased risk in infants with hemangiomas, Ohio-based researchers report in the March issue of the Archives of Dermatology.Lead investigator Dr. Jefferson P. Lomenick told Reuters Health that the approach "is commonly used to treat large or disfiguring hemangiomas in young infants. While this therapy is usually successful, steroids are notorious for their side effects, one of which is preventing the body from being able to produce its own steroids naturally -- adrenal suppression or adrenal insufficiency. This can be life-threatening in certain situations."To investigate how prevalent this outcome might be, Dr. Lomenick and colleagues at Cincinnati Children's Hospital Medical Center prospectively studied 16 infants who received prompt adrenal axis evaluation after finishing glucocorticoid therapy. Ten healthy infants acted as controls. The mean duration of treatment was 7.2 months."We found," continued Dr. Lomenick, "that only 1 of 16 infants had adrenal insufficiency following completion of therapy, and this infant had resolution of his adrenal suppression when retested 3 months later. We found similar results in a previous retrospective study."Thus, concluded Dr. Lomenick, "persistent adrenal suppression following completion of glucocorticoid therapy -- as used in our Hemangioma Center -- does not appear to be a problem, and concern for this risk should not dissuade physicians from appropriate use of glucocorticoids for this condition."

Antibiotic strategy can reduce burden of trachoma through herd protection

2009-04-03T22:36:00.000-07:00

Frequent mass antibiotic treatment of children can significantly reduce the prevalence of trachoma infection in the overall community, according to a study carried out in rural Ethiopia by U.S. and Ethiopian researchers and published in the March 28 issue of The Lancet. The report indicates that treating children four times a year with a single dose of azithromycin lowers the prevalence of the disease even in untreated individuals, a process analogous to that of herd immunity. There is currently no effective vaccine for trachoma. The study's antibiotic strategy appears to be at least as effective as the approach recommended by the World Health Organization (WHO), which is to treat an entire population annually. The researchers, led by Dr. Thomas Lietman of the University of California, San Francisco, conclude that "this approach could provide a realistic long-term strategy for trachoma programmes." Trachoma is caused by Chlamydia trachomatis infection of the eye. The infection causes severe conjunctival inflammation in young children, which in adulthood can lead to trichiasis (inturned eyelashes), causing painful blindness. In trachoma-hyperendemic areas such as parts of Ethiopia, "more than half of children are affected, almost every adult has scarring, and 10-20% of older people have trichiasis," writes Dr. Hugh R. Taylor of the University of Melbourne, Australia, in an accompanying editorial. Dr. Taylor notes that repeated reinfections appear to be necessary for the severe inflammation that leads to ocular scarring. The cluster-randomized trial took place in 12 communities, where each child aged 1-10 years received four single doses per year of oral azithromycin (approximately 20 mg/kg). Children under 1 year were offered a 6-week course of topical 1% tetracycline. Individuals aged 11 years and older did not receive treatment. In a control group of 12 different communities, no treatment for trachoma was given until after the study ended at 12 months. In a third group of 12 communities, all individuals 1 year and older were offered treatment per WHO guidelines: oral azithromycin or, for children younger than 1 and pregnant women, topical tetracycline. The decline in prevalence of ocular chlamydia infection from baseline to 12 months in the children-treated group was 48.4% to 3.6% in the children 10 and under. Importantly, the mean prevalence of infection in those 11 and older, who had not been treated, also fell significantly, from 15.5% to 8.2%. In the mass-treatment group, the mean prevalence of infection in children aged 10 years and under also declined, from 41.9% to 14.6% over 12 months. However, the latter figure was still significantly higher (p = 0.001) than that for such children in the children-treated group. The prevalence at 12 months in those 11 and older was not significantly different from that in the children-treated group. The researchers suggest that frequent treatment of children could eventually eliminate trachoma infection from the entire community.

Survival in patients with yolk sac tumors has improved significantly

2009-01-07T08:46:00.000-08:00

NEW YORK (Reuters Health) - While yolk sac tumors remain an aggressive form of germ cell cancers with a relatively poor prognosis, the 5-year survival rate has improved significantly over the past decade, particularly in younger patients. In a study published in the December 1 issue of the International Journal of Cancer, Dr. Jay P. Shah and colleagues at Wayne State University in Detroit, Michigan, compared patient characteristics and survival rates in males and females with yolk sac tumors. The investigators used the Surveillance, Epidemiology, and End Results (SEER) Program database from 1973 through 2003 to extract demographic and clinicopathologic information on 788 patients, 451 males and 337 females, with yolk sac tumors.Median age was 23 years for males and 19 years for females; 22 years for whites and 18 years for African-Americans. There was a bimodal distribution for age at diagnosis, with an increased incidence in the first four years of life and again at age 10-30 years. "The bimodal age distribution of yolk sac tumors generates the hypothesis that sex steroids may play a role in selected yolk sac tumors," Dr. Shah believes.Most primary tumors were gonadal in origin, with the testis the primary site in 42.6% of tumors and the ovaries the primary site in 32.6%. One-fourth (24.6%) of yolk sac tumors were extragonadal in origin. Males with extragonadal tumors had the shortest 5-year survival rates while males with testicular yolk sac tumors had the longest 5-year survival rates compared with females with either ovarian or extragonadal tumors. Among extragonadal tumors, site of origin differed in males and females. The mediastinum and retroperitoneum were more common in males, while tumors of the heart and soft tissues were more common in females. The median survival for the cohort overall was 87 months and was similar in males and females. The 5-year survival of extragonadal yolk sac tumors was 66%, while it was 86% for gonadal tumors. African-Americans had the worst survival, overall. Survival of both males and females with yolk sac tumors steadily improved from 1973 through 2003. Although the overall survival in all yolk sac tumor patients has improved, the primary sites of origin remain different in males and females and affect prognosis."In general, the epidemiological patterns reveal that pediatric onset (patients) seem to do better then adult onset," Dr. Shah commented in an interview with Reuters Health. "Yolk sac tumors remain an aggressive form of germ cell cancers, but the application of chemotherapy has significantly improved survival over the past few decades," he said. "Both male and female patients should be aggressively treated."

Survival in patients with yolk sac tumors has improved significantly

2009-01-07T08:45:00.000-08:00

HHV8 A subtype tied to aggressive Kaposi's sarcoma

2009-01-07T08:38:00.000-08:00

NEW YORK (Reuters Health) - Of human herpesvirus 8 (HHV8) strains associated with classic Kaposi's sarcoma (KS), the A subtype is associated with rapidly progressive disease, Italian researchers report in the December issue of the Journal of Medical Virology.Dr. Roberta Mancuso of the Don Gnocchi Foundation, Milan, and colleagues note that although the link between HHV8 and KS has been established, much is still unknown.To investigate the pathogenic potential of different HHV8 genotypes, the researchers studied blood, serum and saliva samples from 38 subjects with classic KS.The highest viral loads were detected in saliva, and higher concentrations of lytic antibodies and higher viral loads were observed in patients with fast progressing KS. HHV8 detection in blood was also more frequent in this group of patients.Type A HHV8 was found in 12 of 17 patients with fast progressing diseases. Type C was seen in 6 of 7 patients with slow progressing disease. Detection of the A strain was also associated with higher blood viral loads. The findings, Dr. Mancuso told Reuters Health, "indicate that the A strain of HHV8 might be associated with a more aggressive form of disease with faster progression, and suggest that more aggressive treatments for patients should be envisioned for patients with this type of HHV8."

Drug resistance in myeloproliferative disorders can be overcome

2009-01-07T08:37:00.000-08:00

NEW YORK (Reuters Health) - A newly identified apoptosis pathway is inhibited in cancerous myeloid cells, making them resistant to treatment. However, the researchers who identified this pathway have also discovered how to override its inhibition and restore the cells' susceptibility to chemotherapy. They describe their findings in the December 25th issue of The New England Journal of Medicine.The investigators, led by Dr. Denis R. Alexander at The Babraham Institute in Cambridge, UK, studied cells from patients with chronic myeloid leukemia (CML) or polycythemia vera. A press release from the Institute explains that in normal cells, DNA damage increases the activity of a proton pump in the cell membrane known as sodium-hydrogen exchanger isoform 1 (NHE-1). Activating NHE-1 raises cellular pH, which in turn triggers a deamidation process in which the prosurvival protein Bcl-xL is converted into a form that permits the damaged cells to die. "In our study, we found that the signaling pathway leading from DNA damage to Bcl-xL deamidation and consequent apoptosis is inhibited" in myeloid cells in patients with CML or polycythemia vera, the authors report. "This is the first demonstration of a role for deamidation in human malignancy," according to the press release. The researchers discovered further that in myeloproliferative cancer cells, the Bcl-xL deamidation pathway is being blocked by tyrosine kinases - BCR-ABL in CML and JAK-2 in polycythemia vera. Furthermore, the researchers discovered that by "enforced alkalinization or overexpression of NHE-1" they could reverse inhibition of the Bcl-xL deamidation pathway and restore apoptosis. In fact, in cells from a patient with CML who developed resistance to the BCR-ABL inhibitor imatinib, "the effects of imatinib resistance could be bypassed by NHE-1 overexpression, which caused increased intracellular pH and apoptosis, or by enforced alkalinization, which caused increased Bcl-xL deamidation and apoptosis." "It is...notable that an increase in the expression of NHE-1 by a factor of 2 to 3 was sufficient to increase Bcl-xL deamidation and triple the level of apoptosis in imatinib-resistant CML cells," the researchers write. "Therefore, targeted stimulation of Bcl-xL deamidation provides a potential route for circumventing resistance to tyrosine kinase inhibitors and perhaps also for eradicating leukemic stem cells."

High hCG levels in pregnancy linked to reduced breast cancer risk

2009-01-07T08:36:00.001-08:00

NEW YORK (Reuters Health) - Higher human chorionic gonadotropin (hCG) levels during pregnancy may lower a woman's risk of breast cancer, according to a report in the December 1st American Journal of Epidemiology.Childbearing provides lifetime protection against breast cancer, the authors explain, but the biologic reasons for this benefit are not understood. Researchers in Europe and the United States, led by Dr. Annekatrin Lukanova at the German Cancer Research Center in Heidelberg, used data from the Northern Sweden Maternity Cohort to address the theory that elevations in circulating hCG and alpha-fetoprotein (AFP) during the first trimester of pregnancy have a long-term protective effect against breast cancer risk.The researchers found no overall association between breast cancer and either hormone. They did find, however, that there was a trend toward lower breast cancer risk for women with hCG levels in the top tertile, compared with women with hCG levels in the lowest tertile.The protection afforded by higher hCG levels was limited to women diagnosed after the median lag time to cancer diagnosis (14 years), the report indicates. AFP concentrations were not associated with breast cancer risk in any of the overall or subgroup analyses."Although the results of the current study must be regarded as suggestive and should be interpreted with caution, they are consistent with a protective effect of elevated hCG levels during pregnancy on long-term risk of breast cancer," the investigators conclude.

Androgen deprivation for prostate cancer does not worsen cardiovascular mortality

2009-01-07T08:34:00.000-08:00

NEW YORK (Reuters Health) - Androgen deprivation with GnRH agonists for men with locally advanced prostate cancer is known to increase the risk of cardiovascular disease, but it does not appear to increase cardiovascular mortality, according to a report in the December 1st issue of the Journal of Clinical Oncology."While our study supports the continued use of GnRH agonists in clinical situations that warrant such treatment and where the benefit in terms of cancer control has been established -- typically the treatment of more advanced or aggressive prostate cancer -- clinicians should keep in mind the risks of diabetes and cardiovascular disease and help their patients adopt strategies to reduce those risks (such as education, screening for diabetes and cardiac disease, and lifestyle modification)," Dr. Jason A. Efstathiou told Reuters Health. Dr. Efstathiou from Massachusetts General Hospital, Boston, and colleagues evaluated the relationship between GnRH agonists and cardiovascular mortality using data from the Radiation Therapy Oncology Group (RTOG) protocol 85-31, a randomized trial of men treated with radiation therapy with or without adjuvant goserelin for locally advanced prostate cancer. In multiple regression analyses, adjuvant goserelin treatment was not associated with cardiovascular mortality or with time to cardiovascular mortality, the authors report. In contrast, prevalent cardiovascular disease and diabetes were significantly associated with greater cardiovascular mortality and with a shortened time to cardiovascular mortality. "In the recent claims-based SEER-Medicare analysis by Dr. Keating that first reported an association between GnRH agonists and incident non-fatal coronary heart disease and myocardial infarction, the effect was modest (16% and 11% increased risk, respectively), and this may not translate into an apparent increase in cardiovascular death," Dr. Efstathiou pointed out."Further studies are planned to evaluate adverse effects of GnRH agonist therapy, including cardiovascular death, in men with earlier-stage prostate cancer who are expected to have very favorable outcomes from their prostate cancer, and for whom the role of GnRH agonists is not as well defined," Dr. Efstathiou said. "Treatment decisions need to carefully weigh potential risks and benefits."

High insulin level is a risk factor for postmenopausal breast cancer

2009-01-07T08:33:00.000-08:00

NEW YORK (Reuters Health) - Data from the Women's Health Initiative Observational Study show that hyperinsulinemia is an independent risk factor for breast cancer.Study investigators, led by Dr. Marc J. Gunter at Albert Einstein College of Medicine in the Bronx, New York, examined the association between incident breast cancer and serologic parameters at study entry in 835 women who later developed breast cancer and 816 who did not. All of the women were postmenopausal and none were diabetic at baseline.In the January 7 issue of the Journal of the National Cancer Institute, the researchers report a positive association between insulin levels and breast cancer risk, with a hazard ratio of 1.46 for the highest versus the lowest quartile of insulin level.The association between insulin and breast cancer risk varied depending on whether or not the women took hormone therapy. On multivariate analysis, insulin level was linked with breast cancer risk only in those who did not use exogenous hormones, with a hazard ratio of 2.40 for the highest versus the lowest quartile of insulin level. In hormone nonusers, obesity was also associated with breast cancer risk, with a hazard ratio of 2.12 for a body mass index (BMI) of at least 30 versus 18 to less than 25. Adjusting for insulin level attenuated this association, however.Fasting levels of endogenous estradiol were also linked with cancer risk, with a hazard ratio of 1.59 for the highest versus the lowest tertile.Given that high levels of insulin and endogenous estradiol raise the risk for postmenopausal breast cancer -- and largely account for the link between obesity and breast cancer -- efforts to bring down fasting insulin or circulating estrogen levels "through weight loss or increased physical activity or via pharmacologic approaches" might be indicated, the researchers conclude.

Low CEA after resection of colorectal liver metastases predicts better survival odds

2009-01-07T08:29:00.000-08:00

NEW YORK (Reuters Health) - Patients with the lowest carcinoembryonic antigen (CEA) levels after liver resection for colorectal metastases have the highest survival rates, according to a report in the December issue of the Archives of Surgery.CEA blood level is the most commonly used tumor marker to monitor patients after resection of primary colorectal cancer and colorectal liver metastases, the authors explain, but few studies have investigated its prognostic value among patients undergoing resection of colorectal liver metastases. Dr. Daniel Jaeck from Hopitaux Universitaires de Strasbourg-Universite Louis Pasteur, Strasbourg, France, and colleagues evaluated the value of CEA measurements obtained a week before and 6 weeks after surgery to predict cure after resection of colorectal liver metastases in 213 patients. Five-year overall and disease-free survival rates were highest (50.2% and 21.9%, respectively) among patients with normal preoperative and postoperative CEA levels, the authors report. They were lower (38.5% and 18.3%, respectively) for patients with elevated preoperative and normal postoperative CEA levels, and lowest (0.0% and 0.0%, respectively) for patients with elevated preoperative and postoperative CEA levels. "Normalization of CEA levels 6 weeks after colorectal liver metastases resection may indicate improved long-term outcomes in these patients," the investigators say."CEA levels as early as 6 weeks after surgery may be helpful in assigning patients to adjuvant chemotherapy after resection of colorectal liver metastases," the authors conclude.

No overall reduction in cancer risk seen again with antioxidants

2009-01-07T08:27:00.000-08:00

NEW YORK (Reuters Health) - In the large, randomized Women's Antioxidant Cardiovascular Study, participants who took beta carotene, vitamin C, vitamin E, or a combination of supplements had no significant reductions in their risk of cancer.The trial, which involved 7,627 women who were followed for an average of 9.4 years, is reported in the January 7 issue of the Journal of the National Cancer Institute by Dr. Jennifer Lin and colleagues at Harvard Medical School in Boston.The placebo-controlled trial was a 2 x 2 x 2 factorial design, testing 500 mg ascorbic acid daily, 600 IU alpha-tocopherol every other day, and 50 mg beta-carotene every other day. Overall, 624 women developed incident invasive cancers, and 176 died from their disease. Compared with women who took placebo, relative risks for developing cancer were 1.11 in the vitamin C group, 0.93 in the vitamin E group, and 1.00 in the beta carotene group. Relative risks for cancer mortality were 1.28 in women who took vitamin C, 0.87 in those who took vitamin E, and 0.84 in the beta carotene group.In summary, Dr. Lin and her colleagues write: "We observed no overall associations of the three antioxidant supplements, taken singly or combined, with total cancer incidence or mortality. Duration of supplementation also did not appear to alter the associations of these supplements with risk of cancer or mortality due to cancer." These results "suggest that there are no overall benefits or risks of vitamins C and E and beta carotene supplementation in the primary prevention of total cancer incidence or cancer mortality," the authors conclude. Dr. Demetrius Albanes of the National Cancer Institute in Bethesda, Maryland, notes in an editorial that despite the lack of overall benefits with antioxidants, two of the study's findings "deserve additional mention." First, there was a trend toward protection against colorectal cancer with vitamin E supplementation. Second, there was an elevated lung cancer risk in the women who took beta carotene supplements.Dr. Albanes adds, "Null trials or those with unexpected outcomes should not ... be viewed as failures; they have and will continue to shed light on the causes of cancer and help us discover the means for its prevention."

Younger men with depression at risk for severe post-prostatectomy pain

2009-01-07T08:26:00.000-08:00

NEW YORK (Reuters Health) - Younger age, symptoms of depression, and severe pain during the immediate post-operative period are significant predictors of severe pain during recovery from radical prostatectomy, prospective study findings indicate.These results imply that "pain once manifested is not easily converted despite a generous analgesic treatment," Swedish investigators explain in the December 9 issue of BMC Nursing. "This may be more evident in ... younger and depressive patients, who might benefit from a more aggressive therapy instituted in the very early postoperative period." Dr. Kerstin Wickstrom Ene, at Sahlgrenska University in Gothenburg, and associates examined factors potentially associated with post-operative pain intensity as assessed by visual analogue scale (0-100 mm) among men undergoing radical prostatectomy (mean age 63 years, range 43-73). VAS pain score > 30 mm was interpreted as inadequate analgesia, and severe pain was defined as VAS > 70 mm.Routine treatments for postoperative pain were continuous epidural analgesia, intrathecal analgesia, or systemic opioid analgesia. Patients were asked about pain at 4 hours after surgery, and about "worst pain" experienced during the last 24 hours at intervals of 24, 48, and 72 hours. Among the 155 patients, one out of four patients experienced severe pain. The only demographic factor associated with a pain level > VAS 30 mm was younger age (p = 0.044).Sixteen patients had symptoms of depression determined the day prior to surgery. Depression correlated with postoperative pain (p = 0.020), and predicted a pain level higher than VAS 70 mm (p = 0.0071). Anxiety level did not affect the pain experience.Overall, intrathecal analgesia was most effective. Epidural analgesia was associated with higher pain levels on day 2 (p < 0.001), whereas patients treated with systemic drugs required more opiates (p < 0.001).In multivariate analysis, "the probability that VAS would exceed 30 mm and 70 mm was predicted only by previous VAS value," Dr. Ene and colleagues report. They recommend that "patients who wake up after surgery with insufficient pain relief should be treated immediately to avoid further pain."

Outcome good with brachytherapy for women with breast implants and breast cancer

2008-12-07T05:58:00.002-08:00

CHICAGO (Reuters Health) - Breast brachytherapy not only avoids tissue contracture around breast implants in women with breast augmentation who develop breast cancer, the approach achieves better tumor control with fewer complications and entails a significantly shorter treatment course than whole breast irradiation. That's according to a Scottsdale, Arizona, surgeon who reported the findings here Monday at the annual meeting of the Radiological Society of North America (RSNA 2008). "I think this will ultimately become the treatment of choice for women with breast augmentation (augs)," Dr. Robert R. Kuske of the University of Arizona and the Arizona Oncology Services in Scottsdale, told Reuters Health. "At the moment, though, I am the only one on the planet doing this."Dr. Kuske presented his results with brachytherapy in 70 women with breast augmentation who developed breast cancers and had undergone lumpectomy."These women received their augs 10 to 20 years ago, and they are now getting to the age where breast cancer becomes an issue. These women literally comprise one-third of my practice," he said."Whole breast irradiation means that radiation wraps around the aug. The tissue around it can contract, which can be very painful," he explained. "With brachytherapy, only a very small percentage of the aug is exposed. Catheters deliver biologically intense radiation to the area around the lumpectomy only. We get better tumor control, fewer complications, better cosmetic outcome -- and the kicker is that it requires a five-day course of treatment as opposed to six and a half weeks (with whole breast irradiation)."Cosmesis was rated as excellent in 91% of patients and good in the remaining 9%. There were no cases with fair-to-poor results. "Normally, with whole breast irradiation, 15%-20% of patients have a fair-to-poor outcome and 55% of women with augs have a fair-to-poor outcome.""I place the brachytherapy catheters under CT guidance. I haven't had any cases of implant puncture and I've never had to replace an implant," Dr. Kuske said. "I use brachytherapy in my nonaugmented patients as well, because it is so incredibly accurate," he added. "We are enrolling patients without implants now to study the efficacy of brachytherapy in the general breast cancer population." Approximately 3,300 of the goal of 4,300 patients have been enrolled to date.

Radiotherapy safe for prostate cancer in HIV-infected patients

2008-12-07T05:58:00.001-08:00

NEW YORK (Reuters Health) - The results of small study suggest that radiotherapy can be safely used to treat prostate cancer in HIV-infected men, having no long-term effect on CD4+ cell count or viral load. When considering radiotherapy for prostate cancer, there is no reason that HIV-infected patients should be treated differently than their HIV-negative peers, senior author Dr. Anthony M. Berson, from St. Vincent's Hospital in New York, and colleagues conclude. The study, reported in the November issue of Urology, included 14 HIV-infected patients with prostate cancer who were treated with external beam radiotherapy, brachytherapy, or both. PSA level, CD4+ cell count, and viral load were assessed at baseline and again at latest follow-up, which ranged from 8 to 73 months.During follow-up, only one patient had a PSA level that was still above 1.1 ng/mL, the report indicates. The average CD4+ cell count rose slightly during follow-up from 523 to 577 cells/microliter. The lowest final count was 200 cells/microliter, the investigators note. Only two patients experienced an increase in viral load. Radiotherapy was not associated with any unusual urinary, rectal, or sexual complications, and no infections were seen in the study group, Dr. Berson's team states.The researchers call for larger studies to definitively assess morbidity and mortality for HIV-infected patients treated for prostate cancer.

Socioeconomic, racial disparities seen in head and neck cancer prognosis

2008-12-07T05:54:00.000-08:00

NEW YORK (Reuters Health) - Poor patients and African Americans face a worse prognosis than other patients with head and neck cancer, according to a report in the November 15th issue of Cancer."The head and neck cancer manuscript is the first in a series of manuscripts we have written to examine disparities in cancer," Dr. Michael Cheung told Reuters Health. "We have observed disparities in a number of different cancers, from esophageal cancer to gynecologic and urologic malignancies." Dr. Cheung and colleagues at the University of Miami Miller School of Medicine, Florida, sought to determine the impact of race, ethnicity, and socioeconomic status on outcomes for almost 21,000 patients with cancers of the head and neck diagnosed between 1998 and 2002. Median survival times were significantly higher for whites (40 months) than for African Americans (21 months), for Hispanics (47 months) than for non-Hispanics (37 months), and for women (41 months) than for men (36 months), the authors report. Patients living in communities with poverty rates above 15% presented with head and neck cancer at a significantly earlier age, and median survival times were decreased across all age groups in such communities. Alcohol consumption and tobacco use also independently affected survival in patients with head and neck cancer, the report indicates. Other independent predictors of survival included tumor location, tumor stage, tumor grade, surgical extirpation, and adjuvant treatment modalities such as chemotherapy and radiotherapy, the investigators say. The inequalities seen in the study are "not explained completely by demographics, comorbid conditions, or undertreatment because poor outcomes continued to be observed after correcting for these factors," the researchers note. "As clinicians, first we need to be aware of such disparities," Dr. Cheung said. "We need to know that certain groups may present at a younger age and may have more aggressive cancer at that age. A delay in diagnosis may turn a potentially treatable cancer into a cancer that is unresectable." He continued, "We need to be vigilant in early cancer detection by following the recommended cancer screening guidelines and be pro-active in patient education on risk reduction, such as smoking cessation and alcohol consumption." Giving patients information can make a difference. "We also need to be certain that our patients understand their diagnosis and understand where they need to go and who they must see in order for them to receive multimodal care (i.e., surgical oncologist, medical oncologist, radiation oncologist, etc.)," Dr. Cheung concluded. Cancer 2008;113:2797-2806.

Gallstones a risk factor for colorectal adenoma

2008-12-07T05:53:00.000-08:00

NEW YORK (Reuters Health) - Among subjects undergoing colonoscopy screening, cholelithiasis is associated with an increased risk of colorectal adenoma, findings published in the November issue of the American Journal of Gastroenterology indicate. Many studies "have reported a moderately increased risk of colorectal cancer in patients with cholecystectomies," note Dr. Yutaka Yamaji, of the University of Tokyo, Japan, and colleagues write. "In contrast, few reports have been published regarding colorectal adenoma, a precursor of cancer." Moreover, they note, "Very few studies have investigated the association between cholelithiasis without resection and colorectal adenoma, but data indicate that the two are not related." The researchers therefore examined the association between cholelithiasis and colorectal adenoma in 4458 subjects (3053 men, 1405 women) who underwent both ultrasonography and colonoscopy, and completed a questionnaire on lifestyle habits. Overall, 4189 subjects had normal gallbladders while cholelithiasis was detected in 206 subjects and 63 had cholecystectomies. The prevalence of colorectal adenoma was 29.6% in cholelithiasis patients, significantly higher than the 17.7% prevalence in subjects with normal gallbladders (p < 0.001). Only 15.9% (10/63) of cholecystectomy patients developed colorectal adenomas, which was not significantly different from control patients. Cholelithiasis was an independent risk factor for colorectal adenoma (adjusted odds ratio, 1.57) in a multivariate analysis controlling for sex, age, family history of colorectal cancer, alcohol, smoking, and body mass index. A strong association was observed between cholelithiasis and the presence of at least 3 lesions (adjusted OR 2.39) and left-sided colorectal adenomas (adjusted OR 1.82). "We did not detect an association between cholecystectomy and colorectal adenoma, but silent cholelithiasis and colorectal adenoma were related," Dr. Yamaji and colleagues conclude. "Although the mechanism of this association is unclear, it is possible that the carcinogenic properties of bile acid may play a role." Am J Gastroenterol 2008;103:2847-2852.

Parasympathetic nervous system contributes to sleep disruption in breast cancer

2008-11-14T09:04:00.000-08:00

NEW YORK (Reuters Health) - Reduced parasympathetic tone is associated with sleep disruption in women with metastatic breast cancer, according to a report in the October 15th issue of the Journal of Clinical Sleep Medicine."This is the first study to the authors' knowledge to find a connection between poor sleep and dysregulation of parasympathetic nervous system response in women with metastatic breast cancer," Dr. Oxana Palesh told Reuters Health.Dr. Palesh from the University of Rochester, Wilmot Cancer Center, New York, and colleagues note that sleep disruption is common in cancer patients. They sought to determine the relationship between hypothalamic-pituitary-adrenal (HPA) axis dysregulation, vagal functioning, and sleep problems in women with metastatic breast cancer by assessing respiratory sinus arrhythmia (RSA), an important marker of parasympathetic tone. Higher RSA was significantly associated with higher sleep efficiency, less waking after sleep onset, lower average length of nocturnal wake episodes, and a lower self-reported number of hours of sleep during a typical night, the authors report. Hormone use, chemotherapy and radiation treatments, and depression also contributed to sleep disruption, but not as significantly as parasympathetic dysregulation (as reflected by RSA levels). "It was surprising to see that the strongest association was between a parasympathetic nervous system dysregulation and sleep problems even after we considered patients' age, their disease severity, type of treatment, and psychological variables such as pain and stress," Dr. Palesh commented. "This was surprising because in the general population, these variables have shown to account for a significant amount of variance in predicting insomnia." "Given our findings, one of the best interventions for regulation of autonomic functioning is diaphragmatic breathing," Dr. Palesh said. "Any number of stress management techniques would be effective. Examples include but are not limited to biofeedback treatment, hypnosis, visualization exercises, meditation, progressive muscle relaxation, and exercise such as yoga." Dr. Palesh added, "We are also planning a study where we will implement a simple breathing exercise intervention in cancer patients to see whether increasing heart rate variability will mediate improvements in sleep."

Nonrandom X chromosome inactivation seen in BRCA1 mutation carriers

2008-11-14T09:03:00.000-08:00

NEW YORK (Reuters Health) - Skewed inactivation of the X chromosome is more frequent among carriers of a mutation in BRCA1 than among the general population, according to a study by Australian researchers published in the November 5 issue of the Journal of the National Cancer Institute. Furthermore, because the study also found that carriers of the BRCA1 mutation with skewed X inactivation tended to develop breast cancer later in life than did control subjects, the authors suggest that skewed X inactivation provides some protection against cancer. Dr. Amanda B. Spurdle of the Queensland Institute of Medical Research, Brisbane, and colleagues explain that while the inactivation of maternal or paternal X chromosomes in women is normally random, resulting in balanced inactivation, skewed X inactivation has been documented in roughly 2.7%-4.5% of women in the general population. Earlier studies have linked skewed X inactivation to breast or ovarian cancer.In their current study, the researchers examined patterns of X inactivation in blood samples from 1,606 women: 735 healthy control subjects, 313 ovarian cancer patients, 235 breast cancer patients who did not carry mutations in either BRCA1 or BRCA2, and affected and unaffected carriers of mutations in BRCA1 (260) or BRCA2 (63). Skewed X chromosome inactivation was defined at the 90% threshold, that is, at least 90% of the cells examined had to show inactivation of the same X chromosome. The investigators established that skewed X inactivation was 2.7-times more common in women with BRCA1 gene mutations than in controls, and possibly also more common, though less strikingly so, in women with BRCA2 gene mutations. The trend was strongest in mutation carriers who did not have breast or ovarian cancer. "Among BRCA1 mutation carriers, those with skewed X inactivation were older at diagnosis of breast or ovarian cancer than those without skewed X inactivation," the team reports.Dr. Spurdle told Reuters Health that the finding "does raise for discussion the interesting hypothesis that X-linked modifier genes exist, and what these modifier genes might be."

Statins lower PSA levels

2008-11-14T09:02:00.001-08:00

NEW YORK (Reuters Health) - Use of statin drugs leads to a decline in prostate specific antigen (PSA) levels, and this is most pronounced in men with the largest reduction in LDL cholesterol, researchers report. However, senior investigator Dr. Stephen Freedland said in an interview, "Ultimately, whether these (reduced) PSA values are a good thing -- we're reducing prostate cancer risk -- or a bad thing, in that we're missing cancers -- requires more study."In the October 28th issue of the Journal of the National Cancer Institute, Dr. Freedland at Duke University School of Medicine, Durham, North Carolina, and colleagues note that there is some evidence that statin use may cut the risk of advanced prostate cancer. Nevertheless, the influence on PSA levels is unknown.To investigate further, the researchers studied data on more than 1200 men in whom at least one PSA level was available 2 years before and 1 year after starting statin medication at a median age of 60.3 years. Their mean pre-statin PSA level was 0.9 ng/mL. After starting a statin, there was a median LDL decline of 27.5% and a median PSA decline of 4.1%. For every 10% decrease in LDL after statin initiation, there was a corresponding 1.64% drop in PSA levels.In a subgroup of men who would have been prostate biopsy candidates because of pre-statin PSA levels of at least 2.5 ng/mL, those with the highest reduction in LDL (41% or more) had a 17.4% decline in serum PSA.In an accompanying editorial, Dr. Ian M. Thompson of the University of Texas Health Science Center at San Antonio and colleagues note the validity of PSA as a screening biomarker, but point out, "If statins do lower PSA, only a randomized trial with histological end-points can determine whether statins affect a man's risk of prostate cancer."

Estrogen-related receptor tied to tamoxifen resistance in lobular breast cancer

2008-11-14T08:47:00.002-08:00

NEW YORK (Reuters Health) - Using a novel model of invasive lobular breast cancer, US researchers have found that increased expression of estrogen-related receptor (ERR) gamma is associated with resistance to tamoxifen."Until now, this receptor has not been viewed to be of much importance in any type of breast cancer," lead author Dr. Rebecca Riggins, from Georgetown University Medical Center in Washington, DC, said in a statement. "All that was known is that there were more of these receptors in breast cancer than in normal breast tissue."According to the report, which appears in the November 1st issue of Cancer Research, most studies examining endocrine resistance have focused on invasive ductal carcinoma. Although that type of breast cancer is the most common, invasive lobular carcinoma still accounts for up to 15% of new cases. Moreover, while rates of ductal disease have remained fairly stable for the last 20 years, rates of lobular disease continue to climb.In their paper, the research team describes the creation of the first cell culture model of tamoxifen-resistant, invasive lobular breast carcinoma. The cell line they developed showed decreased expression of estrogen receptor alpha and increased expression of ERR-gamma.Knocking out the ERR-gamma overexpression rendered the cells sensitive to tamoxifen. Conversely, forcing ERR-gamma overexpression in standard lobular breast cancer cells made them resistant to tamoxifen. Further analyses showed that ERR-gamma-driven transcription was increased in the tamoxifen-resistant cells, but that inhibition of activator protein 1 (AP1) can enhance or even restore tamoxifen sensitivity. These results, the authors conclude, "support a role for ERR-gamma/AP1 signaling in the development of tamoxifen resistance, and suggest that expression of ERR-gamma may be a marker of poor tamoxifen response."

Needle biopsy may lead to liver tumor dissemination

2008-11-14T08:47:00.001-08:00

NEW YORK (Reuters Health) - The incidence of needle track seeding following biopsy of suspected hepatocellular cancer (HCC) appears to be 2.7%, according to findings of a meta-analysis by UK researchers published in the November issue of Gut.Dr. Darius F. Mirza of University Hospital Birmingham NHS Trust and colleagues note that needle biopsy in such circumstances might be informative, but is not generally recommended because of the risk of seeding. However, the incidence is ill defined.To investigate further, the researchers reviewed the literature and identified seven retrospective and one prospective observational study that reported on needle track seeding in a total of 1340 patients. The team calculated that the incidence of HCC overall was 2.7%, or 0.9% per year. There is some uncertainty, they add, but the highest rates with which the data from the studies are compatible would be 4.0% overall or 1.3% per year. In none of these reported cases of seeding was patient survival affected, and the lesion was successfully treated by resection and local ablation. "Percutaneous image-guided biopsies of liver lesions should not be performed indiscriminately." Dr. Mirza told Reuters Health. "Nevertheless, there is a place for such a guided biopsy, but its use should be restricted to specialized liver transplant centers on a case-by-case basis, following multi-disciplinary review."

Needle biopsy may lead to liver tumor dissemination

2008-11-14T08:46:00.000-08:00

CT screening may detect early lung cancer but can lead to unneeded surgery

2008-11-14T08:44:00.000-08:00

NEW YORK (Reuters Health) - New research indicates that while low-dose CT of the chest can identify lung cancer at an early, more treatable stage, it can also lead to major surgical procedures that uncover no cancer. The Pittsburgh Lung Screening Study (PLuSS) represents the largest single-institution investigation of CT lung cancer screening in current and former cigarette smokers, according to the report in the November 1st issue of the American Journal of Respiratory and Critical Care Medicine.The study included 3642 subjects, between 50 and 79 years of age, who were screened with low-radiation-dose CT. Repeat screening at 1 year was performed in 3423 of the subjects. To be eligible for the study, the subjects had to have smoked at least a half pack of cigarettes per day for 25 years or more and have no history of lung cancer.A noncalcified lung nodule was identified in 40.6% of patients on the initial screening, Dr. David O. Wilson and colleagues, from the University of Pittsburgh, note. Prior to repeat screening, 55.6% of these patients underwent one or more diagnostic imaging studies. During 3 years of follow-up, 80 subjects were found to have lung cancer, including 53 who had a tumor detected on initial screening. Overall, 36 subjects (1%) who had an abnormality detected on the initial or repeat CT screen ended up having a major thoracic operation that resulted in a noncancer diagnosis. Of 82 subjects who underwent thoracotomy or video-assisted thorascopic surgery to rule out malignancy, 28 ultimately received a noncancer diagnosis.Among 69 patients who had non-small cell lung cancer, 40 had stage 1 disease at diagnosis, the report indicates."Our challenge is how to reduce major surgery and morbidity from diagnostic procedures triggered by nodule discovery on CT," Dr. York E. Miller, from the University of Colorado, Denver, writes in a related editorial. "Guidelines for the management of non-calcified pulmonary nodules have been suggested by several groups, with 'watchful waiting' the preferred option in some situations," Dr. Miller adds. These guidelines should be effective in reducing unnecessary surgical procedures if they are adhered to.

CT screening may detect early lung cancer but can lead to unneeded surgery

2008-11-14T08:43:00.000-08:00

Multimodality therapy can cure unresectable colorectal cancer

2008-11-14T08:42:00.000-08:00

NEW YORK (Reuters Health) - A combination of external beam radiotherapy (EBRT), chemotherapy, surgical resection, and intraoperative radiotherapy (IORT) can cure some patients with unresectable colorectal cancer, according to a report in the October issue of the Annals of Surgery."There has been a change in our thinking about patients who come in with otherwise unresectable disease," Dr. Heidi Nelson told Reuters Health. "Over the past 10-15 years we have begun to employ multimodality therapy for patients who historically would not even have been referred to surgeons." Dr. Nelson and colleagues from the Mayo Clinic, Rochester, Minnesota, and colleagues investigated the effects of multimodality therapy on survival, relapse, and the rate and intensity of complications in 146 patients with locally unresectable colorectal cancer. After a median 3.7 years' follow-up, central failure within the IORT boost field occurred in only 3 patients (2%), local failure in 19 patients (13%), regional failure in 6 (4%), and distant failure in 68 (47%), the authors report. Eighty-six percent of patients were free from local recurrence at 5 years, the report indicates, and the estimated 5-year rate of freedom from distant metastasis was 51%. At 5 years, disease-free survival was 43% and overall survival was 52%, the investigators say. There was no perioperative mortality, and the perioperative morbidity rate was 8% (15 complications in 12 patients). Long-term morbidity reached 53% (119 late complications in 77 patients). Age was the only significant predictor for disease-free survival, the researchers note, whereas age, adjuvant therapy, margin status, and pathologic N stage contributed to overall survival. "Not surprisingly, when you use all the tools in your kit, you can heal some of these patients," Dr. Nelson said. "Before you close the door, be sure someone familiar with this approach evaluates the patient." "We will continue to look for ways to reduce systemic failures," Dr. Nelson added. "It's important to treat optimistically and aggressively; intensive follow-up makes a difference even in these patients."

Migraine linked to lower risk of breast cancer

2008-11-14T08:41:00.002-08:00

NEW YORK (Reuters Health) - A history of migraine is strongly associated with reduced risk of hormone receptor-positive invasive breast cancer among postmenopausal women, according to findings from case-control studies conducted in Washington State.Such a link is plausible, the investigators explain in the November issue of Cancer Epidemiology, Biomarkers and Prevention, given migraine's association with falling levels of estrogen during a woman's reproductive years, the higher prevalence of migraine among women compared with men, and the correlation between lifetime estrogen exposure and breast cancer risk.The current analysis by Dr. Robert W. Mathes, at the Fred Hutchinson Cancer Research Center, and colleagues included 1199 cases of invasive ductal carcinoma and 739 cases of invasive lobular carcinoma in women 55 to 79 years of age, and 1474 controls.The relationship between migraine and breast cancer was dependent on the estrogen receptor (ER) and progesterone receptor (PR) status of the tumor. Specifically, compared with women with no history of migraine, those with such a history were at significantly reduced risk of ER+/PR+ ductal carcinoma (odds ratio 0.65), ER+/PR- ductal carcinoma (OR 0.49), and ER+/PR+ lobular carcinoma (OR 0.63).However, the risk of ER-/PR- ductal carcinoma and ER+/PR- lobular carcinoma did not differ significantly between migraineurs and women without migraine. If these findings are replicated, the authors suggest, "The association between migraine and breast cancer risk could expand our understanding of the effect hormonal exposures during a woman's premenopausal years can have on her risk of developing breast cancer when she is postmenopausal."Cancer Epidemiol Biomarkers Prev 2008;17:3116-3122.

Embryo preservation usually successful in cancer patients

2008-11-14T08:41:00.001-08:00

Ovulation induction and embryo cryopreservation is just as successful in women with cancer prior to undergoing gonadotoxic treatment as it is in their healthy peers, new study findings indicate. The investigators, who presented their findings this week at the 64th annual meeting of the American Society of Reproductive Medicine in San Francisco, recommend this means of fertility preservation for cancer patients, as ovarian reserve is severely compromised by chemotherapy and radiation."There have been few data looking at the clinical performance outcome of those few young cancer patients who do seek embryo cryopreservation before gonadotoxic treatments," presenter Dr. Bo Yu told Reuters Health.The research team at New York-Presbyterian Hospital/Columbia University Medical Center conducted a retrospective case-control study to assess the outcomes of egg retrieval and fertilization. Included were 12 patients below age 40 (9 with breast cancer and 1 each with colon cancer, rectal cancer, and synovial cell sarcoma) and 48 age-matched control subjects.The numbers of mature oocytes harvested were similar in the two groups (10.8 vs 9.2), the investigators reported, and the fertilization rates were comparable (64% vs 67%)."In early stage cancer, there is a window of at least 6 weeks after surgery that allows patients to recover from surgery and has been proven to be a safe waiting period before starting chemotherapy or radiation," Dr. Yu noted. "This is the window of opportunity for patients to consider fertility preservation treatments without causing any delay in the start of cancer treatment."For their second presentation, the physicians prospectively evaluated the effect of chemotherapy on ovarian function in 26 young women with stage I and II breast cancer, assessing Mullerian inhibiting substance (MIS, a marker of ovarian reserve), estradiol, follicle stimulating hormone (FSH), and menstrual status. The patients were treated with adriamycin, cyclophosphamide and paclitaxel for 6 months.Chemotherapy decreased ovarian reserve "rapidly and dramatically" as reflected by levels of MIS. Although estradiol and FSH levels recovered quickly, with 58% of women regaining menstrual function by 52 weeks, all MIS levels remained below the normal range of 134 age-matched controls.However, "in spite of the concern of reduced fertility 6 months after chemotherapy, reflected by very low MIS levels, we have documented that pregnancy can occur," the investigators reported.According to Dr. Yu, "When investigating fertility preservation in cancer patients, MIS should be used as the test for ovarian reserve or future fertility potential, and should not be substituted by other indicators such as menstrual status or ovarian endocrine function." She noted that, at her clinic, MIS levels at the time of in vitro fertilization are used to tailor the IVF medication protocol."One thing we hope to achieve through publishing our research is to increase awareness among physicians and patients of the gonadotoxic effects of chemotherapy," she said. "Physicians should counsel patients newly diagnosed with cancer to consider fertility preservation treatments before iatrogenic injury occurs."

3D Doppler evaluation helps identify malignant breast lesions

2008-11-06T03:50:00.001-08:00

NEW YORK (Reuters Health) - Quantitative Doppler ultrasound vascularity measurements, displayed as 3-dimensional images, contribute considerably to the diagnostic evaluation of suspicious breast lesions, researchers report in the November issue of Radiology.Dr. Gerald L. LeCarpentier of the University of Michigan, Ann Arbor, and colleagues studied 78 women with palpable or mammographic abnormalities subsequently confirmed by core or excisional biopsies. Forty-six lesions were benign and 32 were malignant.Thirty-eight patient scans that had been previously partially analyzed were employed as a learning set and 40 new patient scans were used as a test set for previously determined classification indices. In each patient, a series of color Doppler images had been acquired and reconstructed into a volume encompassing the suspicious mass. Six Doppler vascularity measures were calculated. Radiologist grayscale ratings and the patient's age were also taken into account.In both the learning and test sets, speed weighted pixel density (SWPD) along with age and grayscale criteria provided significantly superior diagnostic performance than any single index. The 3-variable index was also more accurate than age and grayscale in combination. The researchers, who note that this index "continues to display promising results," conclude that "SWPD contributes significant independent information."

Whole-genome sequencing identifies novel somatic mutations in AML

2008-11-06T03:48:00.000-08:00

NEW YORK (Reuters Health) - Using next-generation, massively parallel short-read sequencing technology to analyze the genome of tumor cells of a patient with acute myeloid leukemia (AML), researchers have identified eight novel genes with acquired mutations that may be involved in AML pathogenesis."Our study establishes whole-genome sequencing as an unbiased method for discovering cancer-initiating mutations in previously unidentified genes that may respond to targeted therapies," Dr. Elaine R. Mardis, at Washington University School of Medicine in St. Louis, and fellow investigators state in the November 6 issue of Nature.The patient was a woman in her late 50s with normal cytogenetics and with a "typical presentation" of subtype M1 AML. Her initial bone marrow sample contained virtually 100% myeloblasts.The investigators employed whole-genome re-sequencing and variant discovery methods using Illumina/Solexa technology, which they say is associated with reduced cost, a faster data production rate, and requires less DNA for analysis than older technology.Four of the affected genes are associated with cancer pathogenesis, the authors say, including a protein phosphatase, two protocadherin/cadherin family members, and a peptide/drug transporter. Four other genes -- involving G-protein-coupled receptors, a guanine nucleotide exchange factor, and a glutamate receptor gene -- possess "potential functions in metabolic pathways (that) suggest mechanisms by which they could act to promote cancer."The other two variants were in genes that have been previously associated with AML disease progression -- the receptor tyrosine kinase gene FLT3 and the NPM1 gene."All of these mutations (except FLT3) were present in nearly all tumor cells at presentation and again at relapse 11 months later," the authors write, "suggesting that the patient had a single dominant clone containing all of the mutations."Dr. Mardis's team points out that functional validation studies in tissue culture cells and animal models, along with similar sequencing analyses in many other AML patients, will be required to determine the relevance of these variants. However, they don't believe that more limited methodologies, such as candidate gene examination, array analysis, or gene expression profiling, are likely to identify all key mutations in AML.They conclude: "For AML and other types of cancer, whole-genome sequencing may therefore be the only effective means for discovering all the mutations that are relevant for pathogenesis."

Video-assisted lobectomy shortens hospital length of stay

2008-11-03T01:34:00.000-08:00

PHILADELPHIA (Reuters Health) - Hospital length of stay is shorter and perioperative morbidity is significantly lower with video-assisted thoracic surgical (VATS) lobectomy for the treatment of stage I non-small cell lung cancer (NSCLC) than with open thoracotomy and lobectomy.Those findings were reported at CHEST 2008, the 74th annual international assembly of the American College of Chest Physicians, by surgeons at Fox Chase Cancer Center in Philadelphia, Pennsylvania. Dr. Walter Scott described a series of 140 lobectomy patients, 74 of whom underwent VATS and 66 who underwent open thoracotomy. Five of the 74 VATS procedures (6.7%) were converted to open thoracotomies. There was one death in each group.Median length of stay was 7 days with open thoracotomy and 4 days with VATS. Median duration of chest tube placement was 5 days with open chest surgery and 4 days with VATS. The percentage of patients with any complication was 35% with VATS and 42% with open surgery. The mean number of lymph nodes retrieved per patient was 14.7 with VATS and 18.1 with open thoracotomy."The most exciting finding is that our patients go home much sooner when they have VATS compared to open surgery," Dr. Scott said. "Minimally invasive surgical techniques have been used for many decades, but only recently have we applied the technology to patients with lung cancer," he pointed out."Although this study addressed short-term clinical outcomes only, the results support the recommendation that VATS lobectomy is an acceptable if not preferable surgical treatment compared to thoracotomy and lobectomy for patients with clinical stage I NSCLC," Dr. Scott asserted.

Tyrosine kinase inhibition may be beneficial before debulking nephrectomy

2008-11-03T01:33:00.000-08:00

NEW YORK (Reuters Health) - Tyrosine kinase inhibition (TKI) provides significant cytoreduction of renal cell carcinoma (RCC) prior to debulking nephrectomy, according to a report in the October issue of Urology."Preoperative treatment of renal cell carcinoma has the potential to be safely used as an adjunct to surgery," Dr. W. Kimryn Rathmell from the University of North Carolina at Chapel Hill told Reuters Health. Dr. Rathmell and colleagues report on nine patients with locally advanced or metastatic RCC treated with TKI therapy before nephrectomy. Most of them, the investigators say, were initially considered to have unresectable disease because of the bulk of the disease or had another contraindication to immediate surgical resection. Treatment with TKI produced a modest decrease in the size of the primary tumor before surgery (mean, 12.9%; median, 8%), the authors report, but the responses varied widely, ranging from 0.82% for essentially stable disease to 54% with a partial response.Two patients who initially presented with bulky retroperitoneal lymphadenopathy experienced sufficient reductions with TKI to enable them to undergo a complete resection of all disease, the researchers note, and both patients remained free of recurrence without systemic therapy more than a year after nephrectomy. Four patients required dose reductions for adverse events.TKI had no apparent detrimental effect on the debulking nephrectomy, and no patient had issues with wound healing. "More studies are needed to fully evaluate safety, but there are potential benefits to this treatment for patients with either high risk or metastatic disease," Dr. Rathmell said. "We have a prospective neoadjuvant study currently ongoing to further address issues of safety and feasibility for this treatment strategy as an adjunct to surgery."

Urethral catheter-less robotic radical prostatectomy decreases patient discomfort

2008-10-31T02:24:00.002-07:00

NEW YORK (Reuters Health) - Urethral catheter-less robotic radical prostatectomy can decrease patient discomfort and lead to an earlier return of continence, according to a report in the October BJU International.This technique "is more suitable for younger patients but not restricted to them only," Dr. Ashutosh Tewari from Weill Medical College of Cornell University, New York, told Reuters Health.In 10 patients undergoing robotic radical prostatectomy, Dr. Tewari and colleagues tested a custom-made device that splinted the anastomosis while diverting urine directly from the bladder via a narrow tube that exited through a small needle puncture below the gut. The device was designed to be removed after 7 days. Another 20 patients who underwent the same procedure with standard urethral catheters served as controls.None of the patients in the test group had pain in the penile shaft or tip, the researchers note. Two had minimal pain at the suprapubic puncture site, and 2 had discomfort walking and sleeping. In contrast, 18 patients in the control group had pain in the penile shaft or tip, and 14 had discomfort walking and sleeping.Three test-group patients and 8 controls had bladder spasms, but no patient in either group had hematuria, clot retention requiring irrigation, or symptoms suggestive of bladder neck contracture at 6-month follow-up. "Urethral catheter-less robotic radical prostatectomy is feasible, with the advantages of decreased penile shaft and tip pain, and decreased patient discomfort and an earlier return of continence," the investigators conclude."Early results need further validation and studies," Dr. Tewari said. "(We should) continue refining the technique to minimize the patient problems."

U.S. panel urges more cancer research funding

2008-10-31T02:24:00.001-07:00

WASHINGTON (Reuters) - The U.S. government needs to step up funding for cancer research, which has stagnated this decade, as part of an effort to make beating cancer a national priority, a presidential advisory panel said on Thursday.The three-member panel that advises President George W. Bush on cancer-related matters issued a report detailing "troubling trends" including insufficient funding for research into new ways to treat and prevent cancer.The report noted that the U.S. population is getting older and becoming increasingly sedentary, a recipe for more cancer cases; more than a fifth of the population still smokes; the health care system is fragmented; and policymakers have failed to grasp the urgency of making progress against cancer.The panel urged improved coordination of efforts against cancer, better access to health care for Americans as about 45.7 million people have no health insurance, and further efforts to curb tobacco use."Use of clinical trials, basic research, clinical research -- we must have adequate funding for that, and we will continue to push for that," Dr. LaSalle Leffall of Howard University in Washington, who heads the President's Cancer Panel, said in a telephone interview.U.S. biomedical research "is being starved of funding at a pivotal juncture," according to the report.Funding for the National Cancer Institute, part of the U.S. government's research-supporting National Institutes of Health, nearly doubled from 1998 to 2003, but has stagnated since.NCI funding since 2003 has declined 16.5 percent when accounting for inflation, the American Cancer Society said. The NCI received $4.8 billion in the 2008 fiscal year.This means fewer research grants are made and those that are awarded provide less funding than requested by researchers, forcing scientific projects to be scaled back, the American Cancer Society said. Fewer clinical trials are being started and fewer patients are being enrolled in cutting-edge studies than just a few years ago, the group said.Funding for a variety of programs in the United States may be uncertain over the next year, with the federal government committing hundreds of billions of dollars to bail out the financial industry and stimulate the economy.About 565,000 Americans are expected to die this year from various forms of cancer and about 1.4 million are expected to be diagnosed with cancer.Cyclist and testicular cancer survivor Lance Armstrong also serves on the panel. (Editing by Maggie Fox and Vicki Allen)

C. psittaci linked to ocular adnexal MALT lymphoma

2008-10-31T02:23:00.001-07:00

NEW YORK (Reuters Health) - Chlamydophila psittaci may contribute to the development of ocular adnexal mucosa-associated lymphoid tissue (MALT) lymphoma, according to findings published in the September 1st International Journal of Cancer."The demonstration of viability and infectivity of C. psittaci in biological samples from ocular adnexal MALT lymphoma patients has improved the evidence level supporting this bacteria-lymphoma association," Dr. Andres J. M. Ferreri from San Raffaele Scientific Institute, Milan, told Reuters Health. Dr. Ferreri and colleagues assessed the prevalence of C. psittaci infection, as well as the viability and infectivity of C. psittaci, in conjunctival swabs and peripheral blood mononuclear cells (PBMCs) of 20 newly diagnosed ocular adnexal MALT lymphoma patients and 42 healthy blood donors.Fifteen of 20 lymphoma samples contained C. psittaci DNA, the authors report, and C. psittaci was isolated from 5 ocular adnexal MALT lymphoma patients -- from PBMCs of 3 patients and from PBMCs and conjunctival swabs of two patients -- all of whom had C. psittaci DNA-positive lymphomas.C. psittaci was not isolated from any of the healthy blood donors.One month after treatment with doxycycline, only one patient had detectable C. psittaci DNA in post-antibiotic PBMC samples, and no patient had C. psittaci DNA in post-antibiotic conjunctival swabs."Together with H. pylori, C. psittaci is the only bacterium with lymphomagenic potential isolated in pure cultures from lymphoma patients," Dr. Ferreri said."Regarding the prevalence of this infection in lymphoma patients, the establishment of chlamydial strains and other organisms with lymphomagenic capability remains one of the central issues in this field," Dr. Ferreri explained. "Geographical variations in the prevalence of these infections as well as immunological features of these patients favoring the persistence of these infections deserve higher attention."Dr. Ferreri added, "From a therapeutic point of view, the improvement of our knowledge on reinfection and reactivation, as well as drug resistance mechanisms and the identification of cytogenetic features predicting response, will allow us to increase antibiotics' efficacy and to identify the best candidates for this conservative strategy."

Current HRT use is associated with low-grade breast cancer tumors

2008-10-31T02:22:00.000-07:00

NEW YORK (Reuters Health) - Breast cancer patients who use menopausal hormone replacement therapy (HRT) are more likely to have lower-grade tumors and better survival than nonusers, according to results of a Swedish cohort study reported in the current issue of Breast Cancer Research.Dr. Lena U. Rosenberg of the Karolinska Institute in Stockholm assessed a cohort of 2,660 postmenopausal women aged 50-74 years, diagnosed with invasive breast cancer between 1993 and 1995, and followed them through the end of 2003. Median follow-up was 9 years and 3 months. Dr. Rosenberg's team assessed the influence of menopausal HRT before diagnosis on tumor characteristics and breast cancer-specific survival. Women who used HRT before diagnosis were classified as users of estrogen-progestin therapy or estrogen alone. Women were also grouped according to current or past use of HRT, and those who used HRT for less than 5 years or used HRT for 5 or more years. "The favorable survival among current users of hormone therapy was only partly explained by differences in available tumor characteristics and mammographic surveillance," the Swedish team says."We found that use of menopausal hormone therapy at the time of breast cancer diagnosis was associated with lower tumor grade, lobular or other non-ductal histology, positive receptor status, and with a favorable breast cancer survival," Dr. Rosenberg and colleagues write. "Mammographic surveillance did not explain our results," they say. "As tumor grade and receptor status seem to be relatively stable characteristics that are not sensitive to lead time bias, we believe that menopausal hormone therapy induces tumors of certain phenotypes.""The favorable breast cancer survival among current menopausal HRT users was more pronounced in the first five years after diagnosis, than thereafter. This is in line with the finding that more aggressive breast cancer have a peak mortality after around two years, while less aggressive breast cancer have a low but constant mortality for more than ten years after diagnosis. Thus, if our follow-up had lasted longer, the expected survival benefit due to menopausal hormone therapy would have diminished," the Swedish team says."As menopausal HRT increases the risk of breast cancer after only a few years, and this risk disappears shortly after ceasing, menopausal HRT probably acts as a late stage promoter of breast cancer. The epidemiological findings of an association between current menopausal HRT use and low-grade, receptor-positive tumors indicate that menopausal HRT may promote preclinical tumors with less malignant tumor characteristics.""Consequently, we think that current menopausal HRT affects survival through biological effects on the tumor...The highest risks of getting breast cancer are found among long-term, current, or estrogen-progestin users.""That we found a better survival in breast cancer among women currently using HRT is not contradicting the general recommendations to use HRT only if you have symptoms, and for the shortest possible time period," Dr. Rosenberg pointed out in an interview with Reuters Health. "Even if we indicate that the prognosis might be better, getting diagnosed with breast cancer is really worth avoiding."

Current HRT use is associated with low-grade breast cancer tumors

2008-10-31T02:21:00.001-07:00

Current HRT use is associated with low-grade breast cancer tumors

2008-10-31T02:21:00.000-07:00

Several factors increase surgical site infection risk after breast operation

2008-10-31T02:20:00.002-07:00

NEW YORK (Reuters Health) - Suboptimal prophylactic antibiotic dosing and other factors increase the risk of surgical site infection after major breast surgery, according to a report in the September issue of the Journal of the American College of Surgeons.Earlier studies focused on only one or a few potential risk factors for surgical site infections in these patients, the authors explain, thereby limiting conclusions that could be drawn about prevention.Dr. Margaret A. Olsen from Washington University School of Medicine, St. Louis, Missouri, and colleagues identified relevant and new independent risk factors for surgical site infection in women undergoing major breast operations. Over a 4.5-year period, 63 women were diagnosed with 72 surgical site infections within 1 year of their breast surgery.The surgical site infection rate within 1 year of breast operation was 4.9%, the authors report. More infections were classified as superficial (72.2%) than deep (27.8%).Only a few surgical site infections were diagnosed during the original surgical admission (6.3%) or as outpatients (6.3%), the report indicates, whereas most were diagnosed at readmission to the hospital (87.3%).In a multivariate logistic regression analysis, independent risk factors significantly associated with breast surgical site infections included mastectomy, having a breast implant or expander placed during the operation, suboptimal dosing of the prophylactic antibiotic, receiving one or more units of transfused packed red blood cells or platelets during or after the operation, and a history of chest irradiation before the surgery."Identification of these risk factors should allow for development of specific interventions to decrease the risk of surgical site infections," the investigators say, "with the goal of improving outcomes and decreasing morbidity, hospital length of stay, and hospital costs in breast surgery patients.""In addition," they write, "knowledge of these risk factors might allow for better patient selection for reconstruction procedures, and for development of preoperative algorithms to predict surgical site infections, giving surgeons more specific information to tailor their pre- and post-operative management strategies to individual patients."

Rhinovirus on home surfaces transferrable to fingertips

2008-10-31T02:20:00.001-07:00

NEW YORK (Reuters Health) - Surfaces in homes of adults with colds can be contaminated with rhinovirus, which can then be transferred to fingertips following contact, new research shows."Rhinovirus in mucus may contaminate surfaces in the home that are frequently touched, and infectious virus may be transferred to fingertips during activities of daily life," senior researcher Dr. J. Owen Hendley, from the University of Virginia Health System in Charlottesville, told Reuters health. "If the virus on the fingertip is transferred to the eye or nose, a rhinovirus cold may ensue."Dr. Hendley presented his team's findings Tuesday at the combined annual meeting of the Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC) and the Infectious Diseases Society of America (IDSA) in Washington, DC. In the study, the researchers examined rhinovirus contamination in the homes of 30 adults with early common colds. Besides using RT-PCR to detect rhinovirus RNA on surfaces, the team also inoculated samples from 160 home surfaces into standard cell culture to detect infectious virus.Rhinovirus infection was confirmed in 16 subjects. Forty-two percent of surfaces had rhinovirus RNA detected by RT-PCR. The number of positive surfaces per home ranged from 1 to 10 out of 10 tested. Bathroom faucets were the surface most likely to harbor rhinovirus. After the home surfaces were tested, the researchers deposited nasal mucus on objects, then examined the rate of transfer of rhinovirus from surfaces to fingertips during normal daily activities.Transfer of infectious rhinovirus in mucus from objects to fingertips by daily life activities occurred on 23.5% of fingertips after the mucus had dried for one hour. With drying for 24 hours, transfer fell to 4% and after 48 hours, no transfer was noted.Rhinovirus genome was present on 89%, 69%, and 53% of fingertip samples obtained at 1 hour, 24 hours, and 48 hours, respectively, following contamination.Further research, Dr. Hendley said, is needed to determine "whether treatment of surfaces in the home could reduce the frequency of catching rhinovirus colds."

Panitumumab works only in wild-type KRAS colorectal tumors

2008-10-31T02:19:00.000-07:00

NEW YORK (Reuters Health) - Pooled data from four clinical trials confirm that the epidermal growth factor receptor (EGFR) inhibitor panitumumab (Vectibix; Amgen) is only likely to be effective against advanced colorectal cancers containing the wild-type form of the KRAS gene. Compared with patients with mutated KRAS, patients with wild-type KRAS had "superior outcomes for response rate, disease control rate, progression free survival, and overall survival," Dr. Daniel Freeman reported Tuesday in Hollywood, Florida, at the annual meeting on Molecular Markers in Cancer. The meeting is co-sponsored by the American Society of Clinical Oncology, the National Cancer Institute and the European Organization of Research and Treatment of Cancer. The findings stem from 715 patients who received panitumumab monotherapy for metastatic colorectal cancer. Forty-five percent of patients had mutant KRAS tumors and 55% had wild-type KRAS gene, "consistent with mutation rates published in the literature," said principal investigator Dr. Freeman from oncology research at Amgen, Inc., the manufacturer of panitumumab. Responses were observed only in patients with wild-type KRAS status; the objective response rate was 14% in patients with wild-type KRAS status and 0% in patients with mutant KRAS status, Dr. Freeman reported. The disease control rate -- the combination of objective response rate and stable disease -- was 52% in patients with wild-type KRAS versus 14% in patients with mutant KRAS. "The increase in disease control rate resulted in a survival benefit in patients with wild-type KRAS," Dr. Freeman said. Median progression-free survival was nearly twice as long (14.1 weeks vs 7.3 weeks) and median overall survival was 37% longer (8.3 months vs 5.7 months) in patients with wild-type KRAS compared to patients with mutant KRAS.Dr. Bruce E. Johnson from Dana-Farber Cancer Institute, Boston, said "the timing of this analysis is quite pertinent," given the recent publication in The New England Journal of Medicine of a study showing that, when KRAS mutations are present in a colorectal cancer, treatment with the EGFR inhibitor cetuximab (Erbitux) is no better than supportive care alone. In that study, "all the benefit of cetuximab was in the cohort that had wild-type KRAS tumors." Taken together, "the data are quite consistent in showing that mutated KRAS appears to be a very important negative predictor of patients who are unlikely to get a benefit from epidermal growth factor receptor antibody," Dr. Johnson noted.

Tamoxifen may lower osteoporotic fracture risk

2008-10-31T02:18:00.003-07:00

NEW YORK (Reuters Health) - Current use of tamoxifen is associated with a marked reduction in osteoporotic fractures, according to a study published online by the Journal of Clinical Oncology. "Although tamoxifen has been shown to increase bone mineral density in clinical trials, it is less clear whether this significantly affects fracture rates," Dr. Andrew L. Cooke, of CancerCare Manitoba, Winnipeg, Canada, and colleagues write. "Even fewer data are available on skeletal outcomes when tamoxifen is used outside of the context of a clinical trial." The researchers conducted a population-based, case-control study to examine whether tamoxifen use is associated with osteoporotic fractures in routine clinical practice. Using data from the Manitoba Department of Health, the team identified 11,096 women at least 50 years of age with fractures, and compared each with three controls without fracture, matched for age, ethnicity, and comorbidity (n = 32,209). Tamoxifen use was categorized as never used, remote past use, recent past use, and current use. Overall, 324 patients (2.9%) and 1123 controls (3.4%) had a breast cancer diagnosis. Approximately 72% of breast cancer patients reported using tamoxifen at some time. Current tamoxifen use was identified in 105 cases (0.9%) and 459 controls (1.4%). Current tamoxifen use was associated with lower osteoporotic fracture rates (univariate OR = 0.68). Remote or recent past tamoxifen use was not related to osteoporotic fractures. "Women with hip fracture were significantly less likely to be current tamoxifen users (adjusted OR = 0.47)," Dr. Cooke's team reports. "ORs for wrist fractures alone (0.84) and spine fractures alone (0.73) showed a similar trend but were not statistically significant." The authors note that breast cancer was not independently associated with osteoporotic fractures (adjusted OR = 0.95).J Clin Oncol 2008;26

Tamoxifen may lower osteoporotic fracture risk

2008-10-31T02:18:00.002-07:00

Tumor protein predicts survival after pancreatic cancer surgery

2008-10-31T02:18:00.001-07:00

NEW YORK (Reuters Health) - Survival after pancreatectomy for pancreatic cancer is twice as long when the tumor is negative for the calcium-binding protein S100A2 as when tumors express high levels of this protein, a study indicates. The findings were reported in Hollywood, Florida, this week at the annual Molecular Markers in Cancer meeting, co-sponsored by the American Society of Clinical Oncology, the National Cancer Institute and the European Organization of Research and Treatment of Cancer. "While this research is still at a very early stage, we've found that testing for the S100A2 protein could help us identify which patients will be most likely to benefit from surgery, which can be complicated and risky," study leader Dr. Andrew Biankin of the Garvan Institute of Medical Research and Bankstown Hospital, Sydney, Australia, noted in a written statement.In a large cohort of pancreatic patients, Dr. Biankin and colleagues assessed the relationship between disease-specific survival and levels of 17 candidate biomarkers known, or suspected, to be aberrantly expressed in pancreatic cancer. Of the 17 candidate markers examined, the only independent predictor of outcome following surgery was the S100A2 level. Patients with elevated S100A2 tumor expression had a median survival of 8.8 months, compared with 19.4 months in patients whose tumors did not contain this protein. It is noteworthy, the researchers say, that patients with S100A2-negative tumors had a significant survival benefit from pancreatectomy even in the presence of involved surgical margins (median survival 15.7 months; p = 0.0007) or lymph node metastases (median survival 17.4 months; p = 0.0002). In conclusion, Dr. Biankin and colleagues say S100A2 expression "is the best predictor of response to pancreatectomy for pancreatic cancer reported to date, and high S100A2 expression may represent the development of a metastatic phenotype." "Prospective measurement of S100A2 expression in diagnostic biopsies has potential clinical utility as a predictive marker of response to pancreatectomy and other therapies that target loco-regional disease," they add.

Video-assisted lobectomy shortens hospital length of stay

2008-10-31T02:16:00.000-07:00

Late effects of Hodgkin's lymphoma salvage therapy "significant

2008-10-19T07:55:00.002-07:00

High-dose chemoradiotherapy and autologous stem-cell rescue, the standard treatment for patients with relapsed/refractory Hodgkin's lymphoma, is associated with significant late morbidity and mortality, according to a study posted online September 22 ahead of print by the Journal of Clinical Oncology. Dr. Karyn A. Goodman from Memorial Sloan-Kettering Cancer Center, New York, and colleagues evaluated 153 of 218 patients treated by high-dose chemoradiotherapy and autologous stem-cell rescue at Sloan-Kettering from 1985 to 1998 who survived for at least 2 years after treatment. During a median follow up of 11.5 years after rescue therapy, a total of 53 patients died; 33 from Hodgkin's lymphoma and 20 from other causes. Thirteen deaths were caused by second malignancy, with a median time from therapy to second malignancy of 9 years (range, 3 to 18 years). The risk ratio of second malignancy was 6.5 when compared to the general population, but 2.4 when compared with patients with Hodgkin's lymphoma, the researchers report. The global quality of life of the patients was comparable with that of the general population. However, late treatment-related morbidity was "significant, with cardiac, pulmonary, and infertility issues," as well as reduced functioning. "This study confirms that patients with relapsed or refractory Hodgkin's lymphoma who undergo salvage high-dose chemoradiotherapy and stem-cell rescue are at highest risk of death from recurrent Hodgkin's lymphoma," the researchers note. Late effects of therapy are also significant among the increasing number of long-term survivors, "with a 15-year cumulative mortality from second malignancy of 11%," they also point out. It's important to note, Dr. Goodman and colleagues say, that during the past 4 decades, treatment modifications have reduced late effects from conventional therapies. "With the current combined-modality therapy using moderate doses of IFRT and fewer cycles of risk-adapted chemotherapy, cardiac complications and development of second malignancies should diminish."

Moderate physical activity may lower endometrial cancer risk in heavy women

2008-10-19T07:55:00.001-07:00

Physical activity, even at light or moderate intensities, attenuates the risk of endometrial cancer associated with excess weight, according to findings from the American Cancer Society's prospective Cancer Prevention Study II Nutrition Cohort study.Dr. Alpa V. Patel and colleagues at the American Cancer Society in Atlanta identified 466 incident cases of endometrial cancers between 1992 and 2003 among approximately 43,000 postmenopausal women with intact uteri. Questionnaire responses showed that physically active women engaged primarily in low- to moderate-intensity activities, such as walking, biking, aerobics or dancing, equivalent to about 2 hours of moderately paced walking per week. "All measures of physical activity and the avoidance of sedentary behavior were associated with lower endometrial cancer risk," Dr. Patel and her group report in the October 15th issue of the International Journal of Cancer.However, physical activity was strongly associated with reduced risk only among women who were overweight or obese (p = 0.003)."Since physical activity, even in the absence of weight loss, significantly improves insulin sensitivity and has direct effects on bioavailable estrogen," the authors propose that "it is biologically plausible that overweight or obese women engaging in regular physical activity may experience a greater risk reduction compared to active, normal weight women."Dr. Patel's team calls for more research into the link between light-intensity activity and endometrial cancer risk reduction in order to "strengthen public health recommendations in this regard."

Risk-based care lacking for most childhood cancer survivors

2008-10-19T07:54:00.000-07:00

While the majority of survivors of childhood cancer receive regular medical care, few receive care focused on the specific risks resulting from their prior cancer therapy, according to findings published in the September 20th issue of the Journal of Clinical Oncology. "With contemporary therapy, 80% of children diagnosed with cancer will become long-term survivors," Dr. Paul C. Nathan from the Hospital for Sick Children, Toronto, and colleagues write. "Consequently, more than 270,000 survivors of childhood cancer are alive in the United States, many of whom are at risk of long-term morbidity and premature mortality as a result of their therapy."The researchers conducted a cross-sectional survey of health care use with 8522 participants of the Childhood Cancer Survivor Study. The subjects were asked if they had a medical visit in the preceding 2 years. The authors subsequently assessed whether these visits were related to the prior cancer, whether the survivors received advice on how to reduce their risks, and whether screening tests were discussed or ordered.Completion of echocardiograms and mammograms were confirmed in a subset of participants at high risk for cardiomyopathy or breast cancer. The association between demographics, treatment, health status, chronic medical conditions, and heath care use was evaluated.During the 2-year study period, 953 survivors (11.2%) reported receiving no medical care. Overall, 4882 survivors (57.3%) received general medical care, 1166 (13.7%) received general survivor-focused care, and 1521 (17.8%) received recommended risk-based care. Care at a cancer center was reported by only 1246 patients (14.6%).Survivors who were older, male, black, or uninsured were more likely to receive general medical care only. Subjects who had moderate or extreme cancer-related pain or anxiety, poor physical health, or more serious morbidity were more likely to receive risk-based, survivor-focused care.Of 1810 survivors at risk of cardiomyopathy for whom an echocardiogram was indicated, only 511 (28.2%) reported having the procedure. A mammogram was indicated in 414 women based on their high risk of developing breast cancer. Of these, only 169 (40.8%) women reported receiving a mammogram.Subjects who received care in a cancer center were more likely than those who received care elsewhere to have undergone an indicated echocardiogram (53.2% versus 22.3%) or mammogram (62.4% versus 34.6%)."We need to find and test strategies aimed at educating survivors and their primary care physicians about the long-term risks of their cancer therapy, and about the medical care and surveillance testing that is recommended in order to prevent, detect or treat these problems before they have a significant impact on patients' health and quality of life," Dr. Nathan said in an interview with Reuters Health."A major component of this must involve the empowerment of survivors," he noted. "Many survivors are not aware of the kinds of therapy that they received as children and therefore are poorly informed about their long-term risks and the health care strategies needed to reduce those risks," he explained. "We need to give them tools (such as treatment summaries and comprehensive care plans) so that they can advocate with their primary care physicians to ensure that they are receiving optimal care."

Hyperglycemia tied to infection in bone marrow recipients

2008-10-19T07:53:00.000-07:00

Antecedent hyperglycemia is associated with an increased risk of neutropenic infections during bone marrow transplantation (BMT), researchers report in the October issue of Diabetes Care."The findings of our observational study," lead investigator Dr. Rachel L. Derr told Reuters Health, "suggest that treating hyperglycemia aggressively during BMT may reduce hospital infection rates." Dr. Derr of Johns Hopkins Medical Institutions, Baltimore, and colleagues point out that there is some evidence that hyperglycemia is associated with an increased prevalence of nosocomial infections.To determine if this is the case in BMT recipients, the researchers studied 382 patients, 25 of whom had diabetes. Overall, 84 (22%) developed at least one neutropenic infection and 51 developed blood stream infections.In patients who did not receive glucocorticoids during neutropenia, each 10 mg/dL increase in mean pre-neutropenia glucose was associated with an increased risk of any infection (odds ratio, 1.08) and of bloodstream infections (odds ratio, 1.15). In patients who did receive glucocorticoids, the corresponding odds ratios were 1.21 and 1.24.Tight glycemic control during BMT and glucocorticoid treatment, the researchers suggest, may reduce infections.In the meantime, "an interventional trial that randomizes patients to intensive glucose control versus conventional control is needed at this stage to determine the effect of diabetes control on infections during BMT and steroid administration," Dr. Derr concluded.

Soy's protective effect against breast cancer varies by receptor status

2008-10-17T07:04:00.001-07:00

Rather than protecting against breast cancer across the board, high soy food consumption appears to reduce the risk of estrogen receptor (ER)-positive and human epidermal growth factor receptor 2 (HER2)-negative tumors specifically, according to Japanese researchers reporting in the October 1 issue of the International Journal of Cancer.Dr. Takeshi Suzuki, at Aichi Cancer Center Research Institute in Nagoya, and associates conducted a case-control study of 678 breast cancer cases and 3,390 controls matched by age and menopausal status with no history of cancer.The researchers "observed a significantly reduced risk" of breast cancer among women with the highest soy intake who were ER-positive, HER2-negative or both. For the top tertile of soy intake, compared to the lowest, the odds ratio (OR) was 0.74 for ER-positive breast cancer and 0.78 for HER2-negative breast cancer. Soy intake was not significantly associated with HER2-positive or ER-negative tumors, or with progesterone receptor (PR) status. However, Dr. Suzuki's team found that "when the three receptors were jointly examined, a reduced risk was observed only in patients with ER-positive/PR-positive/HER2-negative tumor," with OR = 0.73 for those in the top tertile of soy consumption. "These findings are biologically plausible, and suggest a potential benefit of soybean products in the prevention of breast cancer," the investigators conclude.

Narrow band imaging does not improve colonoscopy miss rate

2008-10-17T07:03:00.001-07:00

Colonoscopy performed with narrow band imaging (NBI) does not improve the miss rate of colorectal neoplasms compared with conventional white light examination, according to a report in the October issue of Gut.NBI uses a light source centered at blue and green that penetrates primarily the mucosa and submucosa, making surface microvessels visible as dark structures, the authors explain. Because the density and shape of microvessels change in neoplasms, NBI could aid in the diagnosis of neoplasms. Dr. Tonya Kaltenbach and colleagues from Stanford University School of Medicine, Palo Alto, California, investigated the neoplasm miss rate during tandem colonoscopy using NBI or white light. A repeat colonoscopy under white light was the reference standard. "We removed any identified lesion at the time of initial detection, such that the endoscopist performed the second examination in a colon putatively cleared of lesions," the researchers explain. "Hence, we defined a 'missed' lesion as one identified during insertion or withdrawal of the second examination."There were 37 missed neoplasms in 34 patients, the authors report, and there was no significant difference in the rate of missed lesions between the NBI (12.6%) and white light groups (12.1%). The characteristics of the missed neoplasms did not differ between the NBI and white light examinations, the report indicates. The neoplasm detection rates did not differ between the NBI and white light colonoscopy exams, the investigators say. The overall adenoma detection rate was 49%. In a multivariate model, lesion size, morphology, and quality of bowel preparation had no significant influence on the association of NBI with neoplasm miss and detection rates. "We did not find NBI to significantly influence the likelihood of missing or detecting a colorectal neoplasm compared to white light," the researchers conclude. "The 12% miss rate observed in our study, however, is approximately half of that reported in a recent systematic review of the published literature on adenoma miss rate determined by tandem colonoscopy." "Future larger, comparative studies of the diagnostic characteristics of specific colonoscope features such as wide angle of view or high definition, CT colonography and other candidate screening modalities are of interest to advance the efficacy of colorectal cancer prevention," they add.

Late effects of Hodgkin's lymphoma salvage therapy "significant

2008-10-17T07:01:00.000-07:00

Moderate physical activity may lower endometrial cancer risk in heavy women

2008-10-17T07:00:00.000-07:00

Outpatient stem cell transplant feasible for multiple myeloma

2008-10-16T06:04:00.000-07:00

As a treatment for multiple myeloma, autologous stem cell transplantation can be performed on an outpatient basis, resulting in shorter hospital stays and low treatment-related mortality, according to a report in the Mayo Clinic Proceedings for October.In the study of 716 patients treated at one center from January 2000 to October 2007, nearly 40% of subjects were able to be treated without hospitalization. Older age and higher serum creatinine levels were predictive of requiring hospitalization and longer stays. "Although outpatient stem cell transplant has been reported previously, our cohort of patients with multiple myeloma undergoing outpatient transplant is, to our knowledge, the largest to date," Dr. Morie A. Gertz, from the Mayo Clinic in Rochester, Minnesota, and colleagues note. The researchers credit their success with outpatient stem cell transplant to a quality initiative instituted by the Mayo Clinic Blood and Marrow Transplant Program. The initiative, which involved the efforts of physicians, nurses, dietitians, pharmacists, and financial specialists, incorporated an electronic ordering system for tests and chemotherapy designed to reduce medical errors. During the study period, 39% of patients completed the transplant procedure on an outpatient basis. The median hospital stay for all patients was 4 days. For patients older than 65 years and those with elevated creatinine levels, however, the median stays were 7 and 9 days, respectively.The 100-day survival rates for patients with low- and high-risk myeloma were 99.5% and 97.2%, respectively, the report indicates

Wheezing illness due to rhinovirus in early childhood linked to asthma risk

2008-10-16T06:03:00.002-07:00

Among viral wheezing illnesses in infancy and early childhood, those due to rhinovirus are most strongly associated with the development of asthma, according to study results published in the October 1st issue of the American Journal of Respiratory and Critical Care Medicine. "Wheezing viral respiratory illnesses during infancy are often the first clinical manifestation of the most common chronic disease of childhood, asthma," Dr. Daniel J. Jackson, of the University of Wisconsin Hospital, Madison, and colleagues write. "However, many children who wheeze with viral infections during infancy will not go on to develop asthma, suggesting a role for virus- and/or host-specific factors in asthma pathogenesis." In a prospective analysis, the researchers examined the relationship between specific viral illnesses and early childhood asthma development in a cohort of 259 children who were followed from birth to age 6. A total of 454 wheezing respiratory illnesses were reported during the first 3 years of life. Of these, a viral etiology was identified in 398. The most common viruses detected were rhinovirus and respiratory syncytial virus (RSV). Overall, 73 of the 259 children (28%) had asthma in the sixth year of life. An increased risk of developing asthma at age 6 years was associated with wheezing with RSV (odds ratio, 2.6), rhinovirus (OR, 9.8), or both (OR, 10.0) from birth to 3 years of age. The team reports that by age 3 years, a stronger association was observed between wheezing with rhinovirus infection and asthma at age 6 (OR, 25.6). Almost 90% of children with rhinovirus-related wheeze in year 3 developed asthma by age 6 years. "Our data clearly link rhinovirus wheezing illnesses during early life and increased asthma risk in later childhood," Dr. Jackson's team concludes. "These findings therefore raise the question: do early rhinovirus illnesses actually cause asthma?" they note. "Alternatively, rhinovirus wheezing episodes might instead serve to reveal children who are already predisposed to this disease on the basis of abnormal lung physiology and/or immune responses."

Hysterectomy for cervical cancer feasible in obese women

2008-10-16T06:03:00.001-07:00

Obesity, in and of itself, should not be a contraindication to perform radical hysterectomy for cervical cancer, according to a study reported in the October issue of Obstetrics and Gynecology.Aside from greater estimated operative blood loss, obese women had comparable intraoperative and postoperative outcomes, including recurrence rates, as their normal-weight peers."Our data strongly support consideration of radical hysterectomy and pelvic lymphadenectomy as definitive treatment for early-stage cervical cancer in morbidly obese women with minimal comorbidities," lead author Dr. Michael Frumovitz, from M. D. Anderson Cancer Center in Houston, and colleagues conclude.The findings are based on a review of 408 women who underwent radical hysterectomy for cervical cancer at Dr. Frumovitz's center from 1990 to 2006.Based on standard body mass index criteria, 155 (38%) women were normal weight, 126 (31%) were overweight, 77 (19%) were obese, and 50 (12%) were morbidly obese, the authors note. No significant differences in age, comorbidities, smoking status, stage, grade, tumor size, or depth of invasion were noted between the groups. Likewise, no weight-based differences in operative time or complications were seen.Median estimated blood loss increased with body mass index, ranging from 500 mL for normal weight women to 850 mL for morbidly obese women (p = 0.001). This difference, however, did not appear to impact postoperative outcomes; the groups were comparable in terms of length of hospital stay, complications, and readmission rate.Women in the different weight groups also had similar pathologic findings, and recurrence rates and cervical cancer-specific mortality were comparable in each group during a median follow-up period of 64 months. "Our findings indicate that radical hysterectomy with pelvic lymphadenectomy in overweight, obese, and morbidly obese women with early-stage cervical cancer is feasible" and such patients can experience outcomes comparable to those of their normal weight peers, the authors state

High blood flow to breast cancer tumors linked to high recurrence risk

2008-10-16T06:02:00.001-07:00

No decline in tumor blood flow plus a high and unchanging tumor metabolism on positron emission tomography, seen during neoadjuvant treatment, is associated with high disease recurrence rates in women with locally advanced breast cancer. The finding, from a study of 53 women, is reported by Dr. David A. Mankoff of the University of Washington in Seattle and colleagues in the September 20 issue of the Journal of Clinical Oncology."The study implies a new way of thinking about measuring tumor response," Dr. Mankoff commented to Reuters Health.The study subjects underwent dynamic PET scanning with the radiotracers fluorine-18 fluorodeoxyglucose (FDG) and oxygen-15 water before and at midpoint of neoadjuvant chemotherapy. The team estimated tumor blood flow with the O-15 water PET study and calculated the FDG metabolic rate (MRFDG) and transport (FDG K1) parameters. They report that "patients with persistent or elevated blood flow and FDG K1 from baseline to mid-therapy had higher recurrence and mortality risks than patients with reductions."Blood flow and transport parameters "remained independent prognosticators of disease-free survival and overall survival," the researchers found. "For example, in the association between blood flow and mortality, a patient with a 5% increase in tumor blood flow had a 67% higher mortality risk compared with a patient with a 5% decrease in tumor blood flow." "The in vivo changes in breast cancer perfusion and metabolism in response to treatment are highly predictive of relapse and survival, and the imaging results add significantly to the ability to predict relapse and survival," Dr. Mankoff said. "These results suggest that this type of imaging measurement is valuable in evaluating the efficacy of treatment, and predicting how that treatment will impact patient survival."The study uncovered "risk factors for tumor recurrence and death that have not been identified before, namely, an imbalance between tumor metabolism and perfusion (too much metabolism per unit perfusion) and a failure to diminish tumor perfusion with treatment," Dr. Mankoff said. "This points to future research to understand the biologic basis of these findings and also suggests new treatment directed at tumor metabolism and/or tumor vasculature in patients with resistant tumors," the researcher concluded.

Radioembolization with microspheres promising for liver metastases

2008-10-16T06:01:00.000-07:00

For some patients with inoperable neuroendocrine tumor liver metastases, radioembolization with selective internal radiation microspheres can achieve relatively long-term responses, according to a report in the September 1st issue of Cancer."This is a good example of the use of spheres to deliver treatment," Dr. David L. Morris told Reuters Health. "The microsphere delivery of a variety of agents will, I think, be of increasing importance and not just in cancer." Dr. Morris from the University of New South Wales, Sydney, Australia, and colleagues assessed the safety and effectiveness of yttrium-90 radioactive resin microspheres in 34 patients with unresectable neuroendocrine tumor liver metastases.At least half the patients who were previously symptomatic reported improvement at 3 months (18/33 patients, 55%) and at 6 months (16/32 patients, 50%).Mean survival was 27.6 months, the investigators say, with 14 patients dying from progressive metastatic disease after a mean of 14.6 months and 20 patients alive with a mean survival of 36.7 months. There was no obvious contributing factor to account for the good to excellent response in 12 patients who remained alive with no recurrence of liver disease after treatment with yttrium-90 microspheres, the researchers note. All patients reported some degree of abdominal pain from 1 week to 1 month after treatment, the report indicates, but only four patients experienced severe pain and vomiting. "It is questionable whether any other therapy previously has achieved such useful results in patients with inoperable disease," the authors conclude. "We would not consider SIR (selective internal radiation microsphere) treatment for patients with operable neuroendocrine tumor liver metastases," Dr. Morris cautioned. "The reason for this is that whilst we have had complete responses in some patients, SIR treatment does have some serious adverse effects, and we certainly don't yet know what the really long-term results are." He added, "I suppose the most important thing I think we need to know is why some patients have done so superbly well and other patients haven't."

Folate curbs p53-mutated colon cancer

2008-10-16T06:00:00.001-07:00

A low-folate diet may increase the risk of colon cancer, but this now appears to be true only of p53-overexpressing cancers, researchers report in the October issue of Gastroenterology.As lead investigator Dr. Eva S. Schernhammer told Reuters Health, "Our findings suggest that the lower colon cancer risk that has been associated with replete folate status is limited to p53-mutated colon cancers."The researchers note in their paper that folate deficiency leads to hypomethylation in the region of the p53 tumor suppressor gene in colon cancer cells, which can be reversed with folic acid supplementation. Dr. Schernhammer of Harvard Medical School, Boston, and colleagues assayed p53 expression in 399 incident colon cancer specimens from participants in the Nurses' Health Study.There was no difference in p53 wild-type tumor incidence between women who consumed less than 200 µg of folate per day and those who consumed 400 µg or more. This was also the case for vitamin B6 intake levels.However, compared to those with the lowest folate intake, women who consumed over 400 µg of folate daily had a relative risk of p53-mutated cancer of 0.54. In addition, compared to women with the lowest vitamin B6 intake, those with the highest had a relative risk for p53-overexpressing (mutated) cancers of 0.57."Given the importance of p53 in tumor suppression," concluded Dr. Schernhammer, "our study offers one potential mechanism by which relative folate deficiency may promote colon carcinogenesis and highlights the importance of continued investigation into the role of dietary folate and other methyl donors in the chemoprevention of colorectal neoplasia."

Rituximab plus ribavirin/interferon effective against hepatitis C-related vasculitis

2008-10-12T06:28:00.001-07:00

Rituximab combined with ribavirin and interferon alpha-2b is a safe and effective treatment for severe refractory mixed cryoglobulinemia vasculitis associated with hepatitis C virus (HCV) infection, according to a pilot study by French researchers reported in the October issue of the Annals of the Rheumatic Diseases. Research published over the past 5 years indicates that rituximab is effective against cryoglobulin production and the resulting inflammatory vascular lesions, the authors note. Nonetheless, about 30% of patients with mixed cryoglobulinemia (MC) continue to have active disease while receiving treatment with anti-CD20 monoclonal antibody or an antiviral. Dr. Patrice Cacoub of the Universite Pierre et Marie Curie, Paris, and colleagues therefore examined whether combining rituximab with pegylated interferon alpha and ribavirin would be more effective. The researchers studied 16 consecutive patients with HCV-associated MC who either were resistant to treatment with interferon alpha-2b (standard or pegylated) and ribavirin or had relapsed following it. Treatment consisted of an intravenous infusion of rituximab 375 mg/m² once a week for 4 weeks, followed 1 month later by Peg-IFNa2b plus ribavirin for 12 months.Based on assessments made an average of 6 months after completion of treatment, 10 of the 16 patients had a complete clinical response, with improvement in all baseline clinical manifestations, such as arthralgia and peripheral neuropathy. Five were partial responders and 1 was a non-responder. Leg ulcers resolved in all patients, and purpura improved in 84.6%, arthralgia in 83.4%, renal involvement in 57.2% and polyneuropathy in 38.4%. Only two patients experienced significant side effects -- worsening of peripheral neuropathy or a flare-up of skin psoriasis in one patient each. "Taken together these data suggest that rituximab combined with Peg-IFNa-ribavirin may act synergistically and represents a good treatment strategy in patients with HCV-MC with severe organ involvement," Dr. Cacoub and colleagues conclude. The researchers also noted that the duration of MC disease was a significant predictive factor. "The duration of MC vasculitis before treatment in the partial or non-responders was 3.6 times longer than in the complete clinical responders."

Endoscopic surgery for early breast cancer may improve aesthetic results

2008-10-12T06:26:00.000-07:00

As a treatment for early breast cancer, endoscopic-assisted skin-sparing mastectomy (SSM) combined with sentinel node biopsy and immediate breast reconstruction with mammary prosthesis may improve aesthetic results without compromising oncologic control, new research suggests."Although breast-conserving surgeries are the most desirable choice for patients with early breast cancer, many have to abandon breast-conserving surgeries due to tumors accompanied by extended intraductal components or multiple tumors," lead author Dr. Ken-ichi Ito, from Shinshu University School of Medicine in Nagano, Japan, said in a statement. "With this new technique, selected patients can be treated for breast cancer without breast deformity."The study, reported in the ANZ Journal of Surgery for October, featured 33 patients who underwent endoscopic-assisted SSM and sentinel node biopsy for primary breast cancer, including 30 in whom immediate reconstruction with a mammary prosthesis was performed.Postoperatively, 21 of the tumors were confirmed to be ductal or lobular carcinoma in situ and 12 were invasive malignancies. Eight of the invasive cancers had a widespread intraductal component.Multicentric cancers were detected in two patients, which made standard breast-conserving surgery difficult, the authors note.During a mean follow-period of 51.2 months, none of the patients had locoregional recurrence or distant metastases.The results suggest that for women with early breast cancer, the endoscopic-assisted approach is a suitable option that may enhance cosmetic outcomes without reducing oncologic safety, the researchers conclude.

NSCLC in never-smokers a separate disease from NSCLC in smokers

2008-10-12T06:24:00.000-07:00

Japanese investigators say that survival rates are better for non-small cell lung cancer (NSCLC) patients who were never-smokers than in NSCLC patients with a history of smoking. Other disease characteristics are different as well between the two populations. As such, NSCLC in never-smokers should be considered a separate disease entity from NSCLC in current and past smokers, say Tokujiro Yano and colleagues at Kyushu University in Fukuoka, Japan, in the September 1 issue of Cancer.The researchers reviewed the medical records of 1,405 patients with primary NSCLC who underwent complete resection between 1974 and 2004. Clinicopathologic variables and postoperative survival were compared for patients who never smoked and those who reported smoking currently or at some time in their past.Dr. Yano's team found a steady increase in the proportion of never-smokers among all NSCLC patients during the 30-year study period, from 15.9% in 1974 to 32.8% by 2004. Women represented 85.8% of NSCLC never-smokers but only 11.2% of NSCLC patients with a history of smoking. The incidence of adenocarcinomas was significantly higher among the never-smokers (87.8%) vs the smokers (49.1%).Also, the researchers found, 40.1% of the NSCLC never-smokers had pathologic stage IA disease, compared with 25.4% of the smokers.Overall survival and cancer-specific survival rates among the never-smoking NSCLC patients was "significantly superior" to NSCLC patients with a history of smoking. The Kyushu University team found factors other than smoking to be significantly associated with postoperative survival on univariate analysis. The factors included gender, histologic type, T classification, and N classification. "A multivariate analysis revealed never-smoking status to be an independent prognostic factor in addition to pathologic T and N classification," Dr. Yano and colleagues report.There is "a need to carefully obtain the smoking history from patients because precise information regarding smoking status is a prerequisite for making an accurate diagnosis of 'never-smoking NSCLC,'" the authors advise

Adding cytarabine to clofarabine induction improves response rate in AML

2008-10-12T06:19:00.000-07:00

Clofarabine plus low-dose cytarabine achieves better response rates than clofarabine alone when used as front-line therapy for older patients with acute myeloid leukemia (AML) or high-risk myelodysplastic syndrome (MDS), according to a report in the September 1st issue of the journal Blood."There are clear limits in the efficacy of standard induction therapy for elderly patients with AML, and much more research is needed," Dr. Stefan Faderl from the University of Texas M. D. Anderson Cancer Center in Houston told Reuters Health. "Clofarabine is only one example in this direction."In 70 previously untreated patients aged 60 years or older with AML or high-risk MDS, Dr. Faderl and colleagues studied the effects of clofarabine 30 mg/m² daily for 5 days with or without cytarabine 20 mg/m² daily for 14 days.Thirty-nine patients (56%) achieved complete remission, the authors report.Complete remission and overall response rates were 63% and 67%, respectively, with the clofarabine-cytarabine combination, vs 31% and 31%, respectively, with clofarabine alone.Response rates declined continuously with age, falling from 80% in patients 60 to 64 years old to 40% in those older than 70 years, the researchers note.Toxicity was comparable for the 2 regimens, the report indicates.Median event-free survival was significantly longer for patients on the combination (7.1 months) than for those on clofarabine-only (1.7 months), the investigators say, but median overall survival, median remission duration, and median survival of complete responders did not differ significantly between the groups. "Although patients on the combination arm benefited with respect to better event-free survival, long-term outcome remains unsatisfying," the researchers write."We are still interested in the clofarabine/cytarabine combination," Dr. Faderl said. "A follow up study will contain the combination followed by a longer consolidation including hypomethylator drugs. There is also still

Cancer incidence increased after liver transplantation

2008-10-12T06:18:00.000-07:00

The risk of de novo cancer is higher in liver transplant recipients than in the general population, according to a study in Finland. The increased incidence is particularly pronounced among children, the researchers report in the October issue of the journal Liver Transplantation."On the basis of our data," Dr. Fredrik Aberg and co-authors note, "1 of 6 liver transplant patients is estimated to develop some form of cancer by 20 years after transplantation."Although posttransplant malignancies are a recognized problem, "more studies are needed to obtain reliable data on cancer risk patterns in an attempt to reach consensus on optimal monitoring of immunosuppression, cancer surveillance programs, and strategies to minimize cancer risk," the authors maintain. Their study included all Finnish patients who received liver transplants at the Helsinki University Central Hospital between 1982 and 2005 (n = 540), linked with the nationwide Finnish Cancer Registry. During 3222 person-years of follow-up, there were 39 de novo cancers in 36 patients (standardized incidence ratio = 2.59) plus 11 basal cell carcinomas of the skin (SIR 3.70).Rates were higher among children < 17 years old (SIR 18.1) than among patients ages 17-39 (SIR 5.77) and patients age 40 and older (SIR 2.27). Time from transplantation to detection of cancer ranged from 4 to 172 months (mean, 61 months).Non-Hodgkin lymphoma, non-melanoma skin cancer, and basal cell carcinoma were the only types to show significantly elevated SIRs (13.9, 38.5, and 3.70, respectively). Of the 8 patients with non-Hodgkin's lymphoma, 4 had cases of post-transplant lymphoproliferative disorder.Risk factors for skin cancer were older age and antibody induction therapy, while those for non-Hodgkin lymphoma were male gender, young age, and the immediate posttransplant period.According to Dr. Aberg's team, "This study points out the importance of cancer surveillance after liver transplantation as well as the need for innovative immunosuppression strategies associated with less cancer risk."In a related editorial, Dr. Ashokkumar Jain at the University of Rochester in New York, and colleagues review other reports of post-liver transplantation de novo cancers. They point out that such reports are difficult to compare, based on authors' inclusion or exclusion of lymphoid malignancies and a wide variation in reported cancer types by region. In general, they note, "The overall rate of de novo solid tumors increases with age at the time of transplant and the length of follow-up, whereas the rate of post-transplant lymphoproliferative disease decreases with age at liver transplantation, with a higher incidence in the first few years post-transplant."

Low risk of cancer cell dissemination during sonohysterography

2008-10-09T09:44:00.001-07:00

Although sonohysterography is associated with transtubal fluid spills, there is little likelihood of endometrial cancer cell dissemination during the procedure, according to a report in the American Journal of Obstetrics and Gynecology for September."Sonohysterography is routinely performed, but we've never really studied whether something that's done all the time is safe or not," Dr. David M. Kushner from University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin, told Reuters Health.Dr. Kushner and colleagues analyzed intraoperative flush fluids collected from 16 women undergoing surgery for endometrial cancer, in order to discover whether transtubal spill of fluid occurs during routine sonohysterography; to identify whether a critical infusion volume exists at which transtubal spill occurs; and to determine the viability of any disseminated cancer cells.In 5 of the 16 patients (31%), transtubal spill occurred with "between 1 and 20 mL of instilled saline solution." After administration of a 50-mL flush, another 7 patients had transtubal fluid spill. Four patients had no intraperitoneal spill.The median volume at which transtubal spill occurred was 20.5 mL, more than twice the median volume required for adequate sonohysterography (8.5 mL), according to the researchers. In 2 women, fluid samples contained adherent cells that had been disseminated during sonohysterography, but these turned out to be benign inflammatory and mesothelial cells. Fluid from another patient contained adenocarcinoma cells that were nonviable based on nonadherence.In a follow-up study, Dr. Kushner said, fluid used during sonohysterography in patients known to have cancer will be retrieved and sent for pathologic analysis, in order to determine whether this approach might be used diagnostically in a manner analogous to bronchial washings during bronchoscopy. In the meantime, Dr. Kushner advises keeping sonohysterography fluid volumes low to minimize the risk for transtubal spill.

Metabolic syndrome raises colorectal cancer risk: study

2008-10-09T09:43:00.001-07:00

In a large US population-based study, individuals with metabolic syndrome had a 75% higher incidence of colorectal cancer in their lifetime. "The results of this study were expected," Dr. Donald A. Garrow, of the Medical University of South Carolina in Charleston, told Reuters Health, pointing out that "individuals with metabolic syndrome have previously been noted to be at higher risk for a number of other cancers." The finding, however, "is concerning," Dr. Garrow said, "because colorectal cancer is often preventable because of the various screening modalities available." Dr. Garrow presented the study findings this week at the 73rd annual scientific meeting of the American College of Gastroenterology in Orlando, Florida. The few studies that have found a potential risk of colorectal cancer among patients with metabolic syndrome were limited by small sample sizes and/or non-US populations, he and colleagues note in meeting materials. In an analysis of 57,561 individuals who participated in the National Health Interview Survey (2002-2003), Dr. Garrow's team found 1,182 who met criteria for metabolic syndrome and 350 who reported a history of colorectal cancer. In patients with metabolic syndrome, the odds ratio for colorectal cancer was 1.75. The risk of colorectal cancer was also increased for Caucasians (OR, 2.58) and for former smokers (OR, 1.55). Current alcohol drinkers were significantly less likely to report a history of colorectal cancer (OR, 0.53). "As it stands now," Dr. Garrow told Reuters Health, "individuals with metabolic syndrome should closely adhere to the guidelines established regarding colorectal cancer screening. Discussion with their primary care doctors regarding the best test for screening is essential."

U.S. says LabCorp ovarian cancer test sales illegal

2008-10-09T09:42:00.000-07:00

Laboratory Corp of America is violating the law by selling an ovarian cancer screening test without regulatory approval, U.S. health officials said Wednesday.The OvaSure test does not fall in a category that can be sold without prior clearance from the agency, the Food and Drug Administration said."Because you do not have marketing clearance or approval from the FDA, marketing OvaSure is in violation of the law," the agency said in a letter dated Sept. 29.The agency told the company to "take prompt action to correct these violations."LabCorp spokesman Eric Lindblom said the company was "disappointed" by the letter. "We are currently in discussions with the FDA over the next steps, and of course we share the FDA's determination to assure patients are protected," he said.The company started selling the blood test in June, saying it could help detect early-stage ovarian cancer in high-risk women.

Elephantiasis elimination program on track

2008-10-09T09:41:00.000-07:00

An international effort to eliminate elephantiasis is on track and has protected millions of children against the disease, proving to be one of the "best buys" in public health, researchers said on Wednesday.Since 2000, the World Health Organization (WHO)-sponsored program has administered more than 1.9 billion treatments to over 570 million people at an estimated cost of $0.50 per person, their analysis showed.The study, published in the Public Library of Science journal PLoS Neglected Tropical Diseases, found that the partnership between drug makers and health groups had put the program on track to eliminate elephantiasis, or lymphatic filariasis (LF), by 2020."Future public-private partnerships will look to the global LF elimination effort as a standout example of how groups can come together to solve a major public health issue," Lorenzo Savioli, director of the WHO's Department of Neglected Diseases, said in a statement.Elephantiasis affects an estimated 120 million people in 83 countries, with another 1.3 billion people at risk, according to the WHO. The disease is caused by parasitic worms spread by mosquitoes that can live for years inside the human body and thrive in the lymphatic system.GlaxoSmithKline's albendazole and Merck & Co's Mectizan are effective treatments, especially if given early, but many in the developing world lack access to them.The two drugmakers have donated their medicines to the program, which has helped to keep costs low, the researchers said. On Wednesday, Glaxo also pledged to deliver an additional 300 million treatments over the next two years.So far, the program has prevented 6.6 million children from acquiring the disease and stopped another 9.5 million people already infected from progressing to more debilitating stages, the study found.The treatments have also offered further benefits, protecting tens of millions of children and women from intestinal worms and other skin diseases, said Eric Ottesen of the Lymphatic Filariasis Support Center in Atlanta, who led the study, and colleagues.

Midlife bone fracture a risk factor for male breast cancer

2008-10-09T09:40:00.000-07:00

In men, the risk of developing breast cancer is increased by having a first-degree relative with breast cancer, being obese and physically inactive, and "somewhat surprisingly," having a bone fracture after the age of 45, researchers report in the October 7th issue of the Journal of the National Cancer Institute. Risk factors for male breast cancer have been largely derived from retrospective studies, which may be affected by participants' limited recall, Dr. Louise Brinton of the National Cancer Institute in Rockville, Maryland, and colleagues note in their report. They analyzed risk factors for male breast cancer among 324,920 men enrolled in the prospective National Institutes of Health-AARP Diet and Health Study. A total of 121 men developed breast cancer during the study. According to the researchers, men with either a male or female first-degree relative with breast cancer had nearly a two-fold increased risk of breast cancer (relative risk, 1.92), compared with men without an affected relative. The risk was particularly elevated among men with an affected sister (RR = 2.25) and among those with both an affected mother and sister (RR = 9.73). Unexpectedly, note the researchers, results showed a greater than two-fold increased risk of breast cancer in men with a bone fracture occurring after age 45 (RR = 2.20). Such an association has not been seen previously, Dr. Brinton and colleagues say, and was "unexpected because breast cancers are less likely to occur among women with fractures." An increased risk of male breast cancer was also associated with obesity (RR = 1.79), and with physical inactivity even after accounting for body mass index. "The identified risk factors show some commonalities with female breast cancer and indicate the importance of hormonal mechanisms," Dr. Brinton and colleagues point out. "Differences in risk factors may reflect unique mechanisms associated with androgens and their ratio to bioavailable estrogens," they conclude.

Facts You Need to Know About Cancer

2008-10-05T07:16:00.000-07:00

One in three people will contract cancer, and one in four will die from the disease.

Within five years, cancer will surpass heart disease as the leading cause of death, according to the American Hospital Association.

In 1994, 1.2 million new cancer cases were added to the more than eight million people in the U.S. who have already been diagnosed with cancer.

Since 1950, the overall cancer incidence has increased by 44 percent; the incidence of breast cancer and male colon cancer by about 60 percent; testis, prostate and kidney by 100 percent; and other cancers, such as malignant melanoma, multiple myeloma and some lymphomas, by over 100 percent.

The estimated annual cost of cancer to the United States, excluding incalculable psychosocial costs, is $110 billion, approximately 2 percent of the GNP.

An estimated 80 million people have health insurance insufficient to cover the costs of a catastrophic illness such as cancer.

Annual production rates for synthetic, carcinogenic and other industrial chemicals exploded from 1 billion pounds in 1940 to more than 500 billion pounds annually during the 1980s.

Recent National Cancer Institute studies have linked: non-Hodgkin's lymphoma and exposure to solvents, oils, and greases; elevated risks for multiple myelorna among men and women employed in the textile and plastic industries; lymphoma among laboratory workers at the U.S. Department of Agriculture; and lung cancer among workers who developed silicosis.

The rates of certain types of cancer among some industrial workers are up to 10 times higher than in the general population. Children of workers handling chemical carcinogens have sharply increase cancer rates. For example, the risks of childhood leukemia are increased two-to-five-fold if, during their mother's pregnancies, their fathers worked with spray paints, dyes or pigments.

Some 75 percent of all cancers develop in those over 55, but notable exceptions include childhood leukemia, testicular and brain cancers - which mainly strike young people and have been increasing at an alarming rate, particularly among peak age groups For example, there has been an approximate 300 percent increase in testicular cancer among those aged 25-34 since the 1950s.

During the 1990s, nearly 2 million women will have been diagnosed with breast cancer and 460,000 will have died. Between 1950 and 1989, the incidence of breast cancer increased by 53 percent.

There has been an approximate doubling in. lung cancer rates in recent decades among non- smokers. A wide range of occupational exposures and urban air pollution have been shown to cause lung cancer.

"Occupational studies have played a major role in identifying well-established environmental carcinogens, such as asbestos, benzene, arsenic, aromatic amines, coal tars, vinyl chloride, chromium, and wood dust." Measures of Progress Against Cancer - Cancer Prevention, Significant Accomplishments 1982-1992, The National Cancer Institute.

"It is well established that primary prevention is the most effective means of disease control. This is particularly true of cancer." Measures of Progress Against Cancer - Cancer Prevention.

"Lack of appreciation of the potential hazards of environmental and food source contaminants, and laws, policies, and regulations protecting and promoting tobacco use worsen the cancer problem and drive up health care costs." Cancer At a Crossroads: A Report to Congress for the Nation, National Cancer Advisory Board, September 1994.

"While individuals have a responsibility to change high-risk behavior, government and society have responsibilities to identify and prevent workplace and environmental hazards, restrict advertising of unsafe products, require accurate product labeling, and provide culturally targeted education about cancer risk and prevention." Cancer At a Crossroads

"The elimination or reduction of exposure to carcinogenic agents is a priority in the prevention of cancer. We are just beginning to understand the full range of health effects resulting from the exposure to occupational and environmental agents and factors." Cancer at a Crossroads

"We spend close to $100 billion a year on cancer treatment in this country. If we are going to get on top of this problem, we absolutely have to focus more on prevention." Dr Devra Lee Davis, senior adviser to the assistant secretary for health and human services. Washington Post, February 14.

"Everyone should know that the 'war on cancer' is largely a fraud." Linus Pauling, two-time Nobel laureate.

"No one should think that because the [Environmental Protection Agency] allows it, a pesticide is safe. No pesticide is safe. They're designed to kill living organisms. They should be treated with respect -including the warnings on the label." Jerome Blondell, EPA's pesticides office. USA Today, February 27,1995.

FACTS AND FIGURES!!!

2008-10-05T07:04:00.000-07:00

Breast cancer is the most commonly diagnosed cancer in women
The risk of breast cancer increases with age and if you live to 90 years your risk of developing this cancer is almost 14%
1.7 million breast cancers were diagnosed worldwide in 2007
465,000 (approx.) women died due to breast cancer in 2007
North America, Australia, Europe have the highest incidence of breast cancer
Large parts of Africa and Asia have the lowest rates
In the last 25 years it incidence has gone up by 30% in the western world
Increased risk of developing breast cancer include -
- Start of menstrual period at an early age
- Menopause later in life
- Having a first or second degree relative with breast cancer
- Obesity
- Consumption of alcohol
- Never having children
- Using contraceptives
- Using hormone replacement therapy during post-menopausal years
- Certain inherited genetic mutations for breast cancer (BRCA1 and/or BRCA2)
Decreased Breast cancer Risk -
- Breast feeding
- Moderate Physical activity
- Maintaining normal weight
- Stop smoking
Breast cancer can be prevented by screening
Early treatment can increase chances of 5 years survival to 98%
Women with a BRCA mutation who get their ovaries surgically removed can reduce their risk of breast cancer by over 50%.
A study from North Carolina State University indicated that Women who performed the act of fellatio and swallow semen regularly (one to two times a week) may reduce their risk of breast cancer by up to 40 percent!!

Body weight, not diabetes, linked with prostate cancer death

2008-10-05T07:03:00.002-07:00

Diabetes, rather than weight, increases the risk of all-cause mortality in men being treated for locally advanced prostate cancer. Conversely, obesity, not prevalent diabetes, increases the risk of prostate cancer-specific mortality, researchers report in the September 10th issue of the Journal of Clinical Oncology.

Obesity is known to be associated with an increased prostate cancer mortality risk -- and most men with diabetes are obese. Therefore, "the metabolic alterations of diabetes have been proposed as the mechanism responsible for greater risk of death from prostate cancer," lead investigator Dr. Matthew R. Smith told Reuters Health.

"In this study, we demonstrate that increased body weight, but not diabetes, is associated with greater prostate cancer mortality," he said.

Dr. Smith of Massachusetts General Hospital, Boston, and colleagues reviewed data on more than 1500 men with locally advanced prostate cancer who were taking part in a randomized clinical trial.

After a median follow-up of more than 8 years, 210 of 765 deaths (27%) were attributed to prostate cancer. After adjustment, prevalent diabetes was associated with significantly greater all-cause and non-prostate cancer mortality (hazard ratio, 2.12).

In contrast, baseline weight was associated with greater prostate cancer-specific mortality (hazard ratio, 1.77), but not all-cause or non-prostate cancer mortality. At 5 years, prostate cancer mortality was 7.5% among patients in the highest weight category compared to 4.1% among those in the lowest.

"These novel observations," continued Dr. Smith, "suggest that the association between obesity and prostate cancer mortality is not due to the metabolic alterations of diabetes."

"Additional research," he concluded, "is needed to determine other potential mechanisms including decreased effectiveness of standard prostate cancer treatments."

Racial disparities seen in endometrial cancer recurrence

2008-10-05T07:03:00.001-07:00

Racial disparities for recurrence-free and overall survival are observed in women with early-stage endometrial cancer, according to the results of a study published in the September 15th issue of the journal Cancer.

"Previous work by our group evaluated racial disparities in endometrial cancer outcome while controlling for potential confounding prognostic factors," lead author Dr. G. Larry Maxwell, of the Uniformed Services University of the Health Sciences, Bethesda, Maryland, and colleagues write.

In a retrospective review of patients with advanced-stage endometrial cancer who participated in treatment trials conducted by the Gynecologic Oncology Group, "we observed that black women had a 20% higher mortality rate compared with white women even when they received similar care in a clinical trial setting," they note.

To further investigate, the researchers retrospectively examined whether recurrence-free and overall survival was different between 110 black and 1049 white patients with stage I or II endometrial cancer treated similarly in a clinical trial setting. Regression and survival analyses were used to analyze demographic, pathologic, treatment, and outcome data. They also noted the post-surgery use of estrogen replacement therapy.

Twenty-five recurrences (20 whites and 5 blacks) and 43 deaths (34 whites and 9 blacks) were reported after a median follow-up of 35 months. Estimates of recurrence-free survival indicated that black women were more likely than white women to experience disease recurrence.

Adjusting for age, body mass index and tumor grade, the relative risk of recurrence for black patients versus white patients was 2.55. When the post-surgical use of estrogen replacement therapy was also considered, the relative risk for black women taking replacement therapy compared with white women who were not was 11.2 (p = 0.0005).

Gene number for mitosis regulator may help detect bladder cancer

2008-10-05T07:02:00.000-07:00

The copy number of the gene for Aurora kinase A (AURKA), a key mitosis regulator, may represent a useful biomarker for bladder cancer, according to a report in the October issue of the Journal of the National Cancer Institute.

In the study, the research team used fluorescence in situ hybridization (FISH) to determine the AURKA copy number in exfoliated cells in urine samples. This test was 87% sensitive and 96.6% specific in detecting bladder cancer with an area under the receiver operating curve of 0.939 (p < 0.001).

"This is the first study in which a single based gene is effective in diagnosing bladder cancer," senior author Dr. Bogdan Czerniak, from the University of Texas, M. D. Anderson Cancer Center in Houston, told Reuters Health.

"There are several biomarker detection tests for bladder cancer and they utilize proteins or DNA," Dr. Czerniak noted. "Our results suggest that AURKA FISH test may be more effective in detecting bladder cancer than conventional approaches such as voided urine cytology."

In laboratory tests, the authors found that forced overexpression of AURKA in urothelial cells caused aneuploidy. Natural overexpression of the gene was seen in lesions from patients with bladder cancer.

Using a training set of 23 bladder cancer patients and 7 healthy controls, the researchers created an AURKA-based model for bladder cancer detection. This was then validated in 100 bladder cancer patients and 148 controls (92 healthy subjects, 56 with benign urologic disease).

The results indicate that the "AURKA FISH test is highly effective in detecting bladder cancer and may enhance the efficiency of conventional techniques such as cytology," Dr. Czerniak said.

Further research, however, will be needed to determine if the test "can have broader applications such as screening of asymptomatic individuals," he added.

Melanogenesis inhibition sensitizes melanoma cells to radiotherapy

2008-10-05T07:01:00.001-07:00

Inhibition of melanogenesis sensitizes melanoma cells in culture to gamma radiation, according to a report in the September 15th International Journal of Cancer.

"I believe that the concept is ready for immediate clinical trials, since chelators of heavy metals (they can chelate copper and in this way inhibit melanogenesis) are already approved by FDA for, for example, treatment of Wilson disease or intoxication with heavy metals," Dr. Andrzej T. Slominski from University of Tennessee Health Science Center, Memphis, told Reuters Health.

Dr. Slominski and colleagues investigated the susceptibility of human melanoma cells with different melanin content to gamma radiation and tested whether melanogenesis inhibition would radiosensitize human melanoma cells.

The susceptibility of melanoma cells to gamma radiation was inversely correlated with their melanin content and tyrosinase activity, the report indicates.

Inhibition of melanin synthesis of human melanoma cells by treatment with N-phenylthiourea (a tyrosinase activity inhibitor) or D-penicillamine (a copper chelator) significantly increased their susceptibility to therapeutic doses of gamma radiation, the authors report.

"We conclude that administration of chemical inhibitors of melanogenesis represents a useful method of augmenting sensitivity to radiotherapy of malignant melanoma and justifies evaluation of its clinical application," the investigators conclude.

Dr. Slominski said he plans "to use melanotic and amelanotic transplantable melanomas in rodents to test whether the inhibition of melanogenesis will sensitize melanotic melanomas to radiation. This will allow us to identify the best inhibitor of melanogenesis and define the best dose as well as an optimal radiation regime."

"The experimental therapy can be started now...using chelating agents and standard radiotherapy," Dr. Slominski added. "This method may be also cost effective in comparison to new drug or chemo- or immunotherapy."

Computer help may eliminate need for double reading of mammograms

2008-10-03T06:12:00.001-07:00

In evaluating screening mammograms for breast cancer, a single reader with computer assistance can perform just as well as two readers, the results of a new study suggest.In the study, reported in The New England Journal of Medicine for October 16 and released ahead of print, the sensitivity, specificity, and positive predictive value for the two reading protocols was nearly the same. Prior research has already established that the sensitivity of screening mammography is significantly improved with two readers rather than one. The researchers note that double reading is standard practice in many European countries but is not widely used in the US. It has been unclear whether single reading with a computer-aided detection system, which relies on various algorithms to analyze digital images, could match the performance of double reading. To investigate, Dr. Fiona J. Gilbert, from the University of Aberdeen in the UK, and colleagues conducted a randomized controlled trial comparing single reading plus computer-aided detection with double reading. Screening mammograms from 31,057 women were included in the analysis. Double reading detected 87.7% of cancers and single reading with computer assistance detected 87.2%, the report shows. With double reading, 3.4% of women were recalled for further assessment, whereas with single reading plus computer assistance, the rate was slightly but significantly higher at 3.9%. The sensitivity, specificity, and positive predictive value with single reading plus computer-aided detection were 87.2%, 96.9%, and 18.0%, respectively. The corresponding values with double reading were 87.7%, 97.4%, and 21.1%. The pathological features of the tumors detected with the two methods were not significantly different, the investigators note. "Double reading, which is recognized as the best method for the detection of small invasive cancers, is often difficult to achieve in practice because of costs and the need for two readers," the authors state. "Where single reading is standard practice, computer-aided detection has the potential to improve cancer-detection rates to the level achieved by double reading."

CT-guided bronchoscopy doesn't improve lung cancer diagnosis

2008-10-03T06:11:00.000-07:00

The use of computed tomography (CT) to steer bronchoscopy doesn't increase the sensitivity of lung cancer detection compared with conventional bronchoscopy, according to researchers at New York University in New York City.Dr. David Ost and colleagues compared the ability of CT scan-guided bronchoscopy with the standard approach to detect peripheral lesions and mediastinal lymph nodes in 50 patients being assessed for lung malignancies. Results were obtained from 25 patients who underwent the CT scan-guided approach and 23 patients who underwent conventional bronchoscopy. Two patients dropped out of the trial.Patients with negative results underwent open surgical biopsy of nodules or lymph nodes, or were followed for more than 2 years if they had a nodule that was less than 1 cm in size. Lung cancer was diagnosed in 36 patients. The diagnosis was made by bronchoscopy in 27 cases (75%). Detection of peripheral lesions was similar with the two scanning techniques, with a sensitivity of 71% for CT scan-guided bronchoscopy and 76% for conventional bronchoscopy.CT-guided bronchoscopy was more sensitive in detecting of malignancies in mediastinal lymph nodes than conventional bronchoscopy was, at 100% and 67%, respectively. However, the difference did not reach statistical significance. "On a per-lymph-node basis, there was a trend toward higher diagnostic accuracy with CT scan guidance," Dr. Ost and colleagues report in the September issue of Chest. "The diagnostic yield was higher in larger lesions and when CT scanning confirmed target entry.""We failed to demonstrate a significant difference between CT scan-guided bronchoscopy and conventional bronchoscopy for the diagnosis of lung cancer in peripheral lesions and mediastinal lymph nodes," the investigators report. "Further study of improved steering methods combined with CT scan guidance for the diagnosis of lung cancer in peripheral lesions is warranted." "Taken together with data from prior case series, this study highlights the need to develop complementary steering adjuncts. Improved steering adjuncts for bronchoscopy may improve the diagnostic yield further and should be the focus of future research," the NYU team writes.In an accompanying editorial, Dr. Armin Ernst of Harvard Medical School in Boston notes that despite its small size the study "does raise questions about the general impact of advanced guidance systems over conventional bronchoscopy, at least in hands of this operator.""Especially at a time when new imaging guidance technologies are being heavily marketed," he adds, "studies that rigorously compare new health-care technologies are necessary, and the article by Ost et al. is a step in the right direction."

High-dose therapy and stem cell transplant useful for resistant Hodgkin disease

2008-10-03T06:10:00.000-07:00

High-dose therapy (HDT) combined with autologous stem cell transplantation (ASCT) may prolong remissions and improve survival in patients with chemoresistant Hodgkin lymphoma, researchers from Seattle report. Although HDT plus ASCT is standard treatment for chemosensitive relapsed/refractory Hodgkin lymphoma, it is frequently not given to patients with chemoresistant disease, Dr. Ajay K. Gopal, from the University of Washington, and colleagues note. Nonetheless, there are few effective therapies for chemoresistant disease and, therefore, the possibility that HDT plus ASCT may improve outcomes is worth exploring.The study, reported in the September 15th issue of Cancer, involved 64 patients with resistant Hodgkin lymphoma who were treated with HDT followed by ASCT at the authors' center from 1986 to 2005. The median age was 35 years and 77% of patients had stage III/IV disease, 80% had a nodular sclerosis histology, and 50% had been treated with radiation in the past. Forty-one percent of patients received regimens including total body irradiation and the remainder did not receive conditioning, the investigators note. During a median follow-up period of 4.2 years, the estimated 5-year overall and progression-free survival rates were 31% and 17%, respectively.On multivariate analysis, the only independent predictor of improved survival was the year of transplant; patients transplanted more recently fared better. For instance, the likelihood of 3-year progression-free survival with treatment in the 1980s was 9%, whereas in the last decade, rates have exceeded 30%. "Until novel effective therapies are developed, the outcome for individuals with chemoresistant Hodgkin lymphoma will continue to be limited," the authors conclude. Still, the current findings suggest that roughly one in three patients with resistant disease will achieve prolonged remission and survival with HDT plus ASCT.

Late heart failure after cell transplant linked to anthracyclines, comorbidities

2008-10-03T06:09:00.000-07:00

Congestive heart failure (CHF) is a well-recognized sequela of heart disease that can occur one or more years after hematopoietic cell transplantation (HCT). New research identifies pre-HCT anthracycline exposure and comorbidities as primary risk factors.Hypertension, obesity, and diabetes are among the diseases that appear to affect the risk, senior author Dr. Smita Bhatia, from City of Hope Cancer Center in Duarte, California, told Reuters Health. Addressing these issues, she added, "can help mitigate the impact of the anthracycline chemotherapy on the heart."The results also indicate that the dose at which anthracyclines adversely impact the heart are lower than previously thought, according to the report in the September 22nd online issue of the Journal of Clinical Oncology.From a cohort of 2,938 patients who survived at least 1 year after undergoing HCT at Dr. Bhatia's center, the team identified 60 patients with late CHF (median ejection fraction = 36.9%). The median age at treatment was 45.3 years and the median time to heart failure was 3.0 years. Sixty-eight percent of patients received autologous HCT.Patients with late CHF received 8.6 cycles of pre-HCT chemotherapy, on average, whereas a matched control group of 166 patients received just 4.9 cycles (p < 0.01).Lifetime anthracycline exposure and body mass index were significantly higher in case patients than in controls. Thirty percent of case patients had multiple chronic comorbidities compared with 13.9% of controls (p < 0.01).On multivariate analysis, an anthracycline dose of 250 mg/meters-squared or higher and multiple chronic comorbidities increased the odds of late CHF by 3.2- and 4.3-fold, respectively. "These results form the basis for identifying high-risk individuals for targeted surveillance, as well as developing preventive strategies in the form of aggressive management of comorbidities," the report concludes.

Cetrorelix offers practical benefits in prep for transcervical resection of endometrium

2008-10-03T06:08:00.001-07:00

The gonadotropin-releasing hormone (GnRH) antagonist analog cetrorelix was generally as effective at inducing endometrial thinning as was the GnRH agonist leuprorelin, British researchers report in the September issue of BJOG : An International Journal of Obstetrics and Gynaecology. The researchers also say that cetrorelix aids in preparing patients for transcervical resection of endometrium (TCRE). Depending on when in the menstrual cycle leuprorelin is started, the process by which it suppresses the endometrium can take up to 3 or 4 weeks, senior author Dr. Bernard Bentick of Royal Shrewsbury Hospital told Reuters Health. This long lead time can cause difficulties for scheduling TCRE, note the report's authors, who add that the use of GnRH antagonists for treatment of endometriosis, fibroids and gynecological cancers is already under investigation.As a GnRH antagonist analog, cetrorelix causes immediate suppression of pituitary hormones and thus ovarian hormones, inducing a menstrual period within 3 days, Dr. Bentick said, and typically suppresses endometrial growth for 6 days from administration of the drug. "Therefore, cetrorelix can be given within a week of endometrial resection/ablation, improving the logistics, while producing fewer side effects," Dr. Bentick said. The researchers first conducted a pilot study in which 10 women about to undergo hysterectomy or hysteroscopy each received a single 3 mg subcutaneous dose of cetrorelix 4 to 8 days before surgery, regardless of the phase of their menstrual cycle. All but 1 of the women had withdrawal bleeding, leading the investigators to conclude that cetrorelix might have the desired effect on the endometrium for TCRE. The primary study was a double-blinded randomized controlled trial involving 100 premenopausal women undergoing TCRE for dysfunctional uterine bleeding. Half received 3.75 mg of leuprorelin acetate 3-4 weeks before surgery, and half received 3 mg cetrorelix acetate 4-7 days before surgery. The amenorrhea rate 6 months after surgery was similarly high in both groups, as was the patients' reported satisfaction with the results of surgery. As a result, although endometrial thinning was significantly greater (according to log-transformed data) in the leuprorelin group, this appeared to have no affect on the clinical outcomes. In addition, hot flashes were significantly (P = 0.0478) less common in the cetrorelix group. "The optimum (possibly higher) dosage of cetrorelix for this purpose has not yet been established," the investigators note.

Heritability of Susceptibility to Mammary Carcinoma

2008-10-02T09:55:00.000-07:00

My champion bichon frise age 12 recently died of a mammary gland tumor with adenocarcinoma which wound up in aggressive tumors in the front leg joints. Can you tell me if there is any evidence of mammary gland tumors having any hereditary links? I have a grand daughter with a pea sized lump which will be excised asap. Both were spayed at age 6 after 3 litters. Is there any chance this is hereditary?

There is nothing in the veterinary literature regarding the heritability of susceptibility to mammary carcinoma. The closest information is that smaller breed dogs are more commonly affected than larger breed dogs. By far, the most important factor in susceptibility is age at the time of spaying: spaying any time prior to the third heat coveys some protection, and spaying before the first heat reduces the risk to almost nothing.

Endoscopic prostatectomy effective in obese patients

2008-10-02T09:53:00.002-07:00

Endoscopic extraperitoneal radical prostatectomy is a feasible surgical technique in obese patients, although the procedure takes longer than in their more slender counterparts, researchers in Germany and Greece report in the September issue of BJU International.Dr. Jens-Uwe Stolzenburg, who developed the technique, told Reuters Heath that "obesity is now a significant health issue in society and the overweight patient presents a considerable challenge to surgeons dealing with prostate cancer."To gauge the effectiveness of the approach, Dr. Stolzenburg of the University of Leipzig and colleagues retrospectively studied data on 500 patients who were treated in this manner.Their age, prostate size and prostate specific antigen levels were similar but 26.8% of the subjects were of normal weight, 56.6% were overweight, and 16.8% were obese.Pelvic lymph node dissection was conducted in 218 patients and nerve-sparing prostatectomy was performed in 123 who were potent before the operation. No patients were converted to open surgery.There were no between-group differences in transfusion rates or duration of catheterization.Overall mean operative time was 149 minutes. However, continued Dr. Stolzenburg, "the operation took approximately 20 minutes longer in the obese group, but otherwise all operative parameters were the same. At six months there was no significant difference between the groups in urinary continence or in complications encountered."The approach, he concluded, "is not contraindicated in obesity and provides a safe and effective surgical treatment for prostate cancer in our increasingly overweight society."

Computer help may eliminate need for double reading of mammograms

2008-10-02T09:53:00.001-07:00

Nephron-sparing surgery may improve survival in some renal cancer patients

2008-10-02T09:52:00.001-07:00

New research suggests that preserving as much tissue as possible during nephrectomy may enhance the survival of renal cancer patients with reduced kidney function at baseline. "Since many studies have shown no difference in survival from cancer when only part of the kidney is removed compared to when the entire kidney is removed, this work raises the question about whether the treatment may be more harmful than the cancer in some cases," lead author Dr. Joseph A. Pettus, from Wake Forest University Baptist Hospital in Winston-Salem, North Carolina, told Reuters Health."The take-home message here is that preoperative glomerular filtration rate (GFR) impacts survival, and we should do whatever we can to try and preserve kidney function when managing kidney tumors."The results, which appear in the Mayo Clinic Proceedings for October, are based on a study of 1479 patients who underwent partial or radical nephrectomy for a localized renal tumor. The patients were treated at Memorial Sloan Kettering Cancer Center in New York from January 4, 1995 to June 9, 2005. During the study period, the patients' median body mass index increased from 27 to 28 and the baseline estimated GFR dropped from 70 to 63 mL/min/1.73 meters-squared. Multivariate analysis confirmed a significant association between year of surgery and baseline estimated GFR (p < 0.001). After accounting for disease stage, baseline estimated GFR, body mass index, and comorbidity were not significantly linked to disease-free survival. However, moderately (45 to 65 mL/min/1.73 meters-squared) and severely reduced (<45 mL/min/1.73 meters-squared) estimated GFR did increase mortality by 1.5- and 2.8-fold, respectively."Our findings were surprising because they suggest that, with the exception of advanced cancers, preoperative GFR can have a bigger impact on survival after surgery than the cancer itself," Dr. Pettus noted."These findings," the authors conclude, "underscore the importance of considering baseline estimated GFR when devising treatment plans for renal cell tumors, especially among patients with serious comorbidity."

Nephron-sparing surgery may improve survival in some renal cancer patients

2008-10-02T09:51:00.000-07:00

High-dose therapy and stem cell transplant useful for resistant Hodgkin disease

2008-10-02T09:50:00.000-07:00

Late heart failure after cell transplant linked to anthracyclines, comorbidities

2008-10-02T09:48:00.000-07:00

Hormone therapy appears safe for BRCA1 mutation carriers

2008-09-25T07:15:00.001-07:00

Postmenopausal women with BRCA1 mutations can use hormone therapy without fear of increasing their risk of breast cancer, new research indicates. In fact, in this group, hormone therapy may actually reduce the risk."These data are reassuring in suggesting that hormone therapy is probably not contraindicated in women with a BRCA1 mutation," Dr. Steven A. Narod, from the University of Toronto, and colleagues state. "Although the data cannot yet be considered definitive, we observed a statistically significant reduction in the risk of breast cancer following hormone therapy use, in both the unadjusted and adjusted analyses."As reported in the September 23rd online issue of the Journal of the National Cancer Institute, the researchers assessed the risks of hormone therapy in a case-control study of 472 postmenopausal women who are carriers of a BRCA1 mutation. The 236 breast cancer cases were matched to the 236 controls based on age, age at menopause, and type of menopause (surgical or natural).Ever use of hormone therapy cut the risk of breast cancer by 42% compared with never use, the report shows. On further analysis, the researchers found that use of estrogen alone significantly reduced the risk of breast cancer by 49% (p = 0.04). By contrast, although estrogen plus progesterone was tied to a reduced risk of breast cancer, the association was not statistically significant. Although these findings provide some evidence of safety for hormone therapy in BRCA1 carriers, editorialists Dr. Rowan T. Chlebowski and Dr. Ross L. Prentice note, they "are insufficient to reliably inform routine clinical practice." "Decision making regarding menopausal therapies in women at increased risk of breast cancer is complex," state Dr. Chlebowski, from Harbor-UCLA Medical Center in Torrance, California, and Dr. Prentice, from Fred Hutchinson Cancer Research Center in Seattle. They add, "Continued caution in prescribing hormone therapy to women with BRCA1 mutations who are at high risk for breast cancers remains prudent."

Increasing BMI may impact choice of prostate cancer treatment

2008-09-25T07:14:00.001-07:00

Obese patients with prostate cancer appear to be more likely to receive nonsurgical treatments than their normal weight counterparts, research shows. Obese patients with prostate cancer have more aggressive tumors, Dr. Benjamin J. Davies from the University of California, San Francisco, and colleagues note in the August issue of Urology, and population-based cohort studies have reported BMI as an independent risk factor for death from prostate cancer. The investigators looked at the effect of BMI on primary treatment of prostate cancer in 2041 men with clinically localized disease who were first treated between 1995 and 2006. A total of 28.1% of patients had a normal BMI, 50.5% were overweight, 16.5% were obese, and 4.8% were very obese. In analyses adjusting for possible confounding factors, increasing BMI was associated with a greater likelihood of receiving nonsurgical therapies (brachytherapy, external radiation, primary androgen deprivation, and active surveillance) relative to radical prostatectomy (p = 0.003). Compared with normal-weight patients, very obese patients had a 77% greater chance of receiving androgen deprivation therapy and a 59% greater chance of receiving brachytherapy as their primary treatment. Although primary androgen deprivation therapy may be a "reasonable" option for certain patients with nonmetastatic disease, "such therapy cannot be considered curative and such patients are at risk of recurrence as well as the side effects of such therapy," Dr. Davies and colleagues write. Brachytherapy as monotherapy, they note, is a "well-validated oncologic modality for low-risk prostate cancer patients (but) it is not robustly validated for intermediate- and high-risk patients." There are many potential reasons for the demonstrated trend toward nonsurgical approaches to prostate cancer with increasing BMI, including a perception that obese patients have higher perioperative complication rates, the team notes, although "no data support a difference with increasing BMI." "To our knowledge, this is the first study that examines the effect of BMI on patterns of treatment for prostate cancer," the authors note. Further research on patient and physician decision-making is needed to elicit the underlying reasons for the observed trends, they conclude.

High fall risk seen in prostate cancer patients on androgen deprivation therapy

2008-09-25T07:13:00.001-07:00

Older men with prostate cancer who are on long-term androgen deprivation therapy (ADT) often show physical performance deficits that significantly increase their risk for falls and injury, researchers report."Although research has shown that androgen deprivation therapy can lead to lean muscle mass loss and decreased strength, more research is needed to determine if older patients are at a higher risk for falling as a result of androgen deprivation therapy," Dr. Supriya G. Mohile commented to Reuters Health.Dr. Mohile at the University of Rochester, New York, and colleagues conducted functional and physical assessments of 50 men, aged 70 and older (median age, 78 years) receiving ADT for systemic prostate cancer. Impairment in activities of daily living was found in 24% of the patients, 56% had abnormal Short Physical Performance Battery findings, and 22% reported falls during the previous 3 months, the investigators report in the August issue of Urology. Deficits occurred in all subcomponents of the performance battery, including balance, walking, and chair stands. "This study as well as recent research from other investigators really highlights the fact that a significant proportion of older men receiving androgen ablation have deficits in physical performance and either are falling or are at risk for falling," Dr. Mohile told Reuters Health. "The geriatrics literature has shown that falls in older patients are associated with the development of fractures ... and an increased risk of mortality.""Although we are increasingly starting to recognize the need to screen and institute prevention mechanisms for osteoporosis in older men who are to receive androgen ablation, the assessment of fall risk and physical performance is not commonly performed in the clinical setting," Dr. Mohile observed. "A multidimensional comprehensive geriatric assessment (CGA) should be a key part of the treatment approach for older cancer patients (especially aged 70 and over) and can help detect these underlying fall risks and physical performance," Dr. Mohile advised.

Starting hormone therapy soon after PSA doubles after radiotherapy has benefits

2008-09-25T07:11:00.000-07:00

Results of a study indicate a significant benefit to initiating hormonal therapy sooner rather than later in men with early prostate cancer who experience a rapid doubling of their prostate-specific antigen (PSA) level within 6 months of radiation therapy. The research also supports holding off on hormonal therapy in men whose PSA increases more slowly during a longer period of time. This study, the investigators say, helps to further refine the role of PSA doubling time in predicting which patients may benefit from androgen deprivation therapy (ADT) for biochemical failure and which may be "expectantly observed" and spared the toxicity of hormonal therapy. Dr. Eric Horwitz, from Fox Chase Cancer Center, Philadelphia, reported the findings Tuesday in Boston at the American Society for Therapeutic Radiology and Oncology's 50th Annual Meeting.The findings stem from a retrospective look at 432 men with T1-3N0M0 prostate cancer who showed PSA failure by the Phoenix, or Nadir+2, definition (i.e., an increase of at least 2 ng/mL from the lowest PSA reading) following definitive three-dimensional conformal radiation or intensity-modulated radiation therapy alone or with ADT.According to the study team, the immediate use of ADT in patients with PSA doubling time less than 6 months was associated with significant improvements in cause-specific survival, although the benefit was less apparent in patients with longer PSA doubling times. In an interview with Reuters Health, Dr. Horwitz said: "Patients whose PSA doubles in less than 6 months should have treatment sooner rather than later and patients whose PSA doubles in greater than 6 months can be watched." For the entire group, the 7-year freedom from distant metastasis and cause-specific survival were 73% and 77%, respectively. A PSA doubling time of 6 months was the significant breakpoint in the freedom from distant metastasis endpoint for patients who were PSA failures, Dr. Horwitz and colleagues report in meeting materials. The 7-year freedom from distant metastasis was 50% in men with a PSA doubling time less than 6 months compared with 83% for those with a doubling time of greater than 6 months. The 7-year cause-specific survival was 61% and 85%, respectively, in these two groups. The use of ADT was associated with an overall improvement in the 7-year cause-specific survival (68% vs 46%), but the benefit was confined to patients with a PSA doubling time less than 6 months. Summing up, Dr. Horwitz said: "We've been using PSA doubling time to help guide our decision about when to begin hormone therapy, but this study gives us new and critical information that suggests we should start therapy sooner than previously thought for some patients and delay treatment for others."

Prediction models underestimate prevalence of BRCA1/2 mutations in Asians

2008-09-25T07:10:00.000-07:00

Two widely used BRCA 1/2 mutation prediction models -- BRCAPRO and Myriad II -- fail to identify many Asian women bearing germline mutations in the BRCA1 and BRCA2 genes, new study findings indicate. "Our findings indicate that Asian-American women with BRCA mutations may not be referred for genetic testing as often as they should be," lead author Dr. Allison W. Kurian, at California's Stanford University, said in a press statement.Dr. Kurian and co-investigators evaluated the two prediction models among 200 Asian subjects and a matched control group of 200 non-Jewish, non-Hispanic white subjects who underwent testing at four cancer genetics clinics.According to the report in the Journal of Clinical Oncology for October 10, both models accurately predicted the number of white mutation carriers; among 25 documented to have one of the mutations, 24 were predicted by BRCAPRO and 25 by Myriad II.However, among 49 Asian women with a mutation, 25 were predicted by BRCAPRO and 26 by Myriad II. Only BRCAPRO discriminates between BRCA1 and BRCA2 mutation carriers, and genetic testing showed that Asian BRCA2 mutations carriers were six times more prevalent than expected by this model.Dr. Kurian and her associates note that BRCAPRO and Myriad II predict the probability of BRCA1/2 mutations based on personal and family history of breast and ovarian cancer. Because of their availability free of charge through the Internet and "their generally superior performance on validation," these models are widely used in the US to guide clinical testing.The two groups did not differ in their reported family structures or number of affected relatives, leading the authors to conclude that "the observed results are less likely caused by reporting bias, and more likely the result of true racial differences in BRCA1/2 mutation epidemiology."Summing up, Dr. Kurian's team writes, "Further study of racial differences in BRCA1/2 mutation epidemiology, with attention to potential modifiers of hereditary cancer risk, is consequently a high priority for future research

Cetuximab improves survival of patients with head and neck cancer

2008-09-14T23:45:00.000-07:00

Combining cetuximab with platinum-based chemotherapy as a first-line treatment can improve overall survival in patients with recurrent or metastatic squamous-cell carcinoma of the head and neck, according to a report in The New England Journal of Medicine for September 11.

Prior research has shown that cetuximab is useful in treating patients with platinum-resistant recurrent or metastatic head and neck cancer. Whether combining this drug with platinum-based therapy as a first-line treatment was effective, however, was unclear.

To investigate, Dr. Jan B. Vermorken, from Antwerp University Hospital in Belgium, and colleagues assessed survival and other outcomes in 442 patients who were randomized to receive platinum-fluorouracil chemotherapy alone or combined with cetuximab as first-line treatment for their malignancy.

Adding cetuximab to the treatment regimen increased the median overall survival from 7.4 to 10.1 months (p = 0.04), the report shows. Progression-free survival rose from 3.3 to 5.6 months (p < 0.001), and the treatment response rate climbed from 20% to 36% (p < 0.001).

The most common serious (grade 3 or 4) adverse effects in both groups were neutropenia, anemia, and thrombocytopenia, the authors note.

Sepsis was significantly more common in the cetuximab group: 9 patients vs. 1 patient in the control group (p = 0.02). Grade 3 skin reactions and grade 3 or 4 infusion-related reactions were seen in 9% and 3% of cetuximab-treated patients, respectively. No study deaths were attributed to cetuximab use, the report indicates.

"Since the introduction of cisplatin for the treatment of recurrent or metastatic squamous-cell carcinoma of the head and neck approximately 30 years ago, there has been little improvement in survival among patients with this disease," the authors state. "Our finding that the combination of platinum, fluorouracil, and cetuximab significantly improved survival as compared with platinum and fluorouracil alone is therefore notable."

Botulinum toxin A effective for persistent cystitis following cancer treatment

2008-09-14T23:42:00.002-07:00

For patients with radiation or chemical cystitis refractory to standard therapy, submucosal injection of botulinum toxin A (BoNT-A) into the bladder wall appears promising, according to a case series reported in the September issue of BJU International.

Dr. Yao-Chi Chuang, at Chang Gung University College of Medicine in Taiwan, and colleagues treated six patients with cystitis due to pelvic irradiation (four patients with prostate cancer and two with cervical cancer), and two patients with cystitis caused by intravesical instillation of BCG for bladder cancer. All had failed conventional therapy with anticholinergic agents for at least 2 months.

Under sedation or local anesthesia, BoNT-A 100-200 U was injected through a cystoscope into 20 sites in the posterior and lateral wall of the bladder.

Three patients had moderate improvement and four had significant improvement in symptoms lasting for up to 6 months.

Among the patients treated with radiation, mean bladder capacity increased from 105 to 250 mL at 2 months, and urinary frequency declined from 14 to 11 episodes per day.

Results were similar in the patients with BCG cystitis, with improvement in bladder capacity from 110 to 230 mL and urinary frequency reductions from 16 to 12 episodes per day. Perceived pain scores decreased from 8 to 2 on a 10-point visual analog scale. The authors note that inflammatory changes induced in bladder tissue by BCG were markedly reduced 2 months after BoNT-A treatment.

Dr. Chuang's group proposes that "BoNT-A may be effective, regardless of the original aetiology, so long as the detrusor reflex is associated with symptom provocation." They also note that recent findings indicate that the agent has antiinflammatory and analgesic effects.

They call for clinical trials to confirm their findings.

PET scans often lead to treatment changes for recurrent colorectal cancer

2008-09-14T23:42:00.001-07:00

Positron emission tomography (PET) scans revealed additional sites of disease in nearly half of patients with possible recurrent colorectal cancer (CRC), and additional information provided by these scans led to changes in planned treatment for a majority of the patients, according to a study by Australian researchers.

The study, the largest prospective trial of its kind to date, is published in the September issue of The Journal of Nuclear Medicine.

"In our study, PET was able to identify more appropriate and effective treatment for patients with suspected recurrent colon cancer," Dr. Andrew M. Scott of the Ludwig Centre for Cancer Research, Melbourne, told Reuters Health, "and management decisions were made that led to potentially curative treatment, as well as avoiding unnecessary treatment, including major surgery."

All 191 patients in the study had a previous diagnosis of CRC. As determined by conventional imaging, 93 patients (group A) had residual lesions equivocal for recurrent tumor, and 98 patients (group B) had potentially resectable liver or lung metastases.

Pre-PET management plans (for surgery, radiotherapy and/or chemotherapy) were obtained for all patients, and a 12-month follow-up determined both the changes to those plans as the result of PET and the outcomes of treatment.

PET detected additional sites of disease in 48.4% of group A patients and 43.9% of group B patients. In group A, 61 patients (65.6%) had their treatment plans changed on the basis of PET results, and this was true of 48 patients (49.0%) in group B as well.

"These data show the value of PET in the stratification of patients into curative or palliative and surgical or nonsurgical groups," the researchers write.

This study, as well as earlier research, Dr. Scott said, "provides definitive information on the role of PET in patients with suspected recurrent colon cancer, and its impact on patient management. The role of PET in this clinical scenario has therefore been firmly established."

Autofluorescence videoendoscopy improves colon polyp discovery

2008-09-14T23:40:00.000-07:00

Compared to use of white light colonoscopy, a prototype autofluorescence imaging videoendoscopy system (AFI, Olympus Medical Systems) can improve detection of colon polyps, according to results of a pilot study by Japanese investigators.

In particular, lead investigator Dr. Takahisa Matsuda told Reuters Health, the system is useful in detection of flat adenomatous polyps. "The largest advantage... may prove to be the ability to perform faster and more efficient examination without the need for additional attachments to the endoscope and without the time and cost required for dye spraying or infusion."

In the August issue of the American Journal of Gastroenterology, Dr. Matsuda of the National Cancer Center Hospital, Tokyo, and colleagues note that the system provides real-time pseudo-color images. Non-neoplastic lesions are green and neoplastic ones have magenta coloration.

To further investigate how the approach compared with white light colonoscopy, the team had a single experienced colonoscopist use both methods in a random order to examine the right-sided colon including cecum, ascending and transverse colon, in 167 patients.

Use of the AFI system led to the detection of 100 lesions, whereas white light yielded 73. The number of neoplastic lesion was 92 with AFI and 69 with white light.

The results are encouraging, and Dr. Matsuda concluded, "Now, we are planning to start a multi-center randomized controlled trial to clarify the usefulness of the AFI system."