Specific c-K-ras Gene Mutations as a Tumor-Response Marker in Locally Advanced Rectal Cancer Treated With Preoperative Chemoradiotherapy

Background: Forty percent of patients with colorectal cancer develop mutations in the K-ras gene.Objective: Our objective was to evaluate whether the presence of c-K-ras gene mutations is a useful tumor-response marker in patients with locally advanced rectal cancer treated with preoperative chemoradiotherapy.Material and Methods: Thirty seven patients with locally advanced rectal cancer were treated with preoperative chemoradiotherapy. Four to six weeks later, surgery was performed. Specimens were classified according to the UICC-AJC classification. A segment of the tumor was obtained to analyze specific c-K-ras gene mutations. Restriction fragment length polymorphism (RFLP) and single strand confirmation polymorphism (SSCP) techniques were used with a set of probes to detect specific c-K-ras mutations in codons 12, 13, and 61. The 37 patients were divided into Group A (with mutations) and Group B (without mutations).Results: All 37 patients completed the scheduled treatment. Group A consisted of 12 patients, whose tumors were classified and specific c-K-ras mutations were located as follows: eight in codon 12, two in codon 13, and one in codon 61. Group B consisted of 25 patients. The tumors were classified and there were more early-stage tumors in Group A, whereas in Group B there were more advanced-stage tumors (P 5 .05, respectively). The mean follow-up was 36.2 6 18.3 months. All Group A patients survived, whereas 8 of the 25 patients in Group B died due to progressive metastatic disease. Survival in Group A was 100%, whereas in Group B it was 59% (P 5 .03).Conclusions: The presence of specific c-K-ras mutations is an indicator of tumor response in patients with locally advanced rectal cancer treated with preoperative chemoradiotherapy and surgery. Therefore, responding patients may be more amenable to less radical surgical procedures based on c-K-ras mutations.     

Ciprofloxacin in the treatment of chronic bacterial prostatitis: a prospective, non-comparative multicentre clinical trial with long-term follow-up. The German Prostatitis Study Group

The efficacy and safety of ciprofloxacin 500 mg bd for 28 days were assessed in 65 adult males with symptomatic bacterial prostatitis, from eight centres in Germany. Urine and prostatic secretions were obtained for culture. Clinical signs and symptoms were evaluated at 12-18 days during treatment, end of treatment (4-9 days post-treatment), and 1, 3, 6 and 9 months post-treatment. Safety was monitored during and at the end of treatment. E. coli was the most frequent pathogen causing infection (35/62) and Enterococcus faecalis the second most frequent (13/62). The combined bacteriological response by patient determined at return visits 4-9 days post and 1 month post-treatment, respectively, was eradication 48/54 (88.9%), persistence 3/54 (5.6%), eradication with recurrence 1/54 (1.9%) and eradication with reinfection 2/54 (3.7%). The clinical response at 1 month post-treatment was resolution 53/54 (98. 1%) and 1/54 (1.9%) failure. The rates for continued eradication in the extended follow-up were 32/39 (82.1%) after 3 months, 26/34 (76. 4%) after 6 months and 13/22 (59.1%) after 9 months. Nineteen patients experienced at least one adverse event. In two patients the trial was prematurely discontinued due to adverse events.     

Phase II study of etoposide (VP-16) in patients with thyroid cancer with no prior chemotherapy: an Eastern Cooperative Oncology Group Study (E1385)

This study of etoposide in thyroid cancer was designed to determine the activity and toxicity of etoposide in a variety of inoperable, thyroid hormone insensitive, and radio-iodine resistant primary cancers of the thyroid. The patients were required to have an ECOG performance status of at least 3 and no previous exposure to chemotherapy. The etoposide was given at a dose of 140 mg/m² daily for 3 days and every 3 weeks until progression. The study was closed after 18 months because of poor accrual. There were no responses seen among the 10 patients accrued. The toxicity was primarily hematologic. There was no evidence of activity of etoposide in thyroid carcinoma, although this study lacked significant power because of the poor accrual.     

Going the distance: Developing shared web-based learning programmes

Despite a high demand for continuing professional education, it is becoming more challenging to provide education in a resource-limited environment that meets the varied needs of learners. The advent of user-friendly, interactive communication technology led the University of British Columbia in Canada to explore the feasibility of developing a web-based distance learning programme shared by undergraduate and practising therapists to address this problem. Potential benefits and challenges of distance learning, undergraduate web-learning, pilot-test results and an assessment of therapists’ interests and needs are profiled.     

Calorie restriction in nonhuman primates: mechanisms of reduced morbidity and mortality

Long term chronic calorie restriction (CR) of adult nonhuman primates significantly reduces morbidity and increases median age of death. The present review is focused upon an ongoing study of sustained adult- onset calorie restriction, which has been underway for 15 years. Monkeys, initially calorie restricted at about 10 years of age, are now approximately 25 years old. The median life span of these restricted monkeys is increasing, now exceeding that of ad libitum (AL)-fed monkeys. In our laboratory, maximum life span for AL-fed monkeys appears to be about 40 years. Thus, whether CR can also increase maximal life span, as it does in rodents, cannot be determined for at least another 15 years. The earliest detectable positive benefit on morbidity in these monkeys was previously reported as the prevention of obesity. Current evidence, as reviewed here, suggests that much obesity- associated morbidity is also mitigated by sustained calorie restraint in nonhuman primates. Furthermore, probably because of the prevention of obesity, diabetes has also been prevented. Recent findings include the identification of extraordinary changes in the glycogen synthesis pathway, and on the phosphorylation of glycogen synthase in response to insulin. This calorie restriction-induced prevention of morbidity does not require excessive leanness, but is clearly present when body fat is within the normal range of 10 to 22%, and this is likely to be true in humans as well.