Adjuvant chemotherapy for patients with resected Dukes' C and high-risk B2 colon cancer with fluorouracil and levamisole

Carcinoma of the large bowel is the second leading cause of cancer mortality in Singapore. Although the great majority of patients are discovered at a stage where resection with curative intent is possible, almost half of the patients afflicted will die of it. The combination of 5-fluorouracil + levamisole used in patients with curatively resected high risk Dukes B2 and all Dukes' C colon cancers has been shown to reduce cancer recurrence rate and improve overall survival. Since 1990 adjuvant chemotherapy has been recommended for this group of patients. This report describes patients treated in Singapore, their toxicities and their outcome. A total of 341 patients were treated between 1990 and 1996. Treatment compliance was 71.8%. Toxicity was moderate with mainly grade 1-2 nausea and vomiting, diarrhoea, stomatitis, alopecia, and neutropenia. There was 1 treatment-related death. Median recurrence-free interval was 81 months and median survival was not reached at 90 months. This regimen is tolerable. Until further randomised reports comparing 5-fluorouracil + levamisole to other combinations are available, this combination chemotherapy is recommended to patients after surgical resection of the high risk Dukes' B2 and Dukes' C colon cancer to reduce cancer recurrence and improve overall survival.     

Hepatic damage associated with mineral oil deposits

The case of a 33 year old male is reported. Hepatic inflammation and scarring were associated with deposits of mineral oil in portal triads. This is believed to be the first reported case of hepatic damage resulting from mineral oil accumulation. Possible sources of the oil are considered.     

Treatment of rat fibrosarcoma by radiotherapy plus immune adjuvant

Combined radiotherapy and nonspecific adjuvant C. parvum or Piromen treatment of rat tumors show improvement over radiotherapy alone. The most effective protocol, resulting in complete remission in 6 of 6 rats was obtained with C. parvum given i.p. in three doses 1 day prior to tumor X-irradiation of three doses of 1500 R each given on days 1, 4, and 8. Animals receiving the same dose schedule without adjuvant had only partial regression of their tumor. Without adjuvant, increasing the dose to 6000 R also resulted in tumor regression, but at the expense of marked necrosis to the leg. One mechanism for the observed results may be stimulation of the reticulo-endothelial system to produce macrophages activated against the tumor. It is also possible that C. parvum causes increased rate of clearance of soluble antigens released as a result of radiation destruction of the tumor, as suggested by Proctor et al (3).     

Hepatic Retransplantation--an analysis of risk factors associated with outcome

Hepatic retransplantation is controversial because the results are inferior to primary transplants and organs are so scarce. To determine the factors that are associated with poor outcome within the first year following retransplantation, we performed a multivariate analysis, using stepwise logistic regression, of 418 hepatic retransplantations performed at a single institution from November 1987 to December 1993. The minimum follow-up was 1 year. Seven variables were found to be independently associated with subsequent graft failure (defined as either patient death or retransplantation): donor age (odds ratio 2.2 for each 10-year increase over age 45, 95% CI 1.3 to 3.7), female donor sex (odds ratio 1.7, 95% CI 1.05 to 2.7), recipient age (odds ratio 1.6 for each 10-year increase over age 45,95% CI 1.2 to 2.8), need for preoperative mechanical ventilation (odds ratio 1.8, 95% CI 1.1 to 2.9), pretransplant serum creatinine (odds ratio 1.24 for each increase of 1 mg/dl, 95% CI 1.1 to 1.4), pretransplant total serum bilirubin (odds ratio 1.4 for each 10-mg/dl increase over 15 mg/dl, 95% CI 1.1 to 1.8), and the primary immunosuppressant, using tacrolimus as the reference category (odds ratio for cyclosporine-based immunosuppression 3.9, 95% CI 2.3 to 6.8). Although not part of the logistic regression model, the timing of retransplantation was also found to be important, with the overall probability of failure increasing from 0.58 on day 0 to a peak of 0.8 on day 38 and decreasing slowly after that. The implications of these results regarding the appropriateness of retransplantation are discussed.     

Rhabdomyolysis associated with simvastatin-gemfibrozil therapy

Simvastatin is a potent inhibitor of hydroxymethylglutaryl coenzyme A (HMG-CoA) reductase intended for use as a hypocholesterolemic agent. The long-term clinical experience with simvastatin indicates that it is a safe, effective, and well-tolerated hypolipidemic agent. Laboratory adverse events involving elevations of serum transaminase levels and serum creatine kinase (CK) levels to more than three times the upper limit of normal range have been seen in 1.5% and 3.4% of cases, respectively. We describe a case of severe myopathy and rhabdomyolysis associated with concomitant use of simvastatin and gemfibrozil. Seven days after discontinuing administration of gemfibrozil and simvastatin, the patient's condition improved and she was discharged home. Although this is the first report to indicate an association between myopathy and concomitant use of simvastatin and gemfibrozil, we strongly recommend caution and careful monitoring if simvastatin is given to patients receiving gemfibrozil.     

Thrombocytopenia associated with long-term levodopa therapy

A 63-year-old man had severe thrombocytopenia after long-term levodopa therapy. Serologic studies and clinical features indicate that the thrombocytopenia was due to an autoimmune process, presumably similar to that induced by the chemically similar drug methyldopa. Direct allergy to levodopa was ruled out by controlled challenge of the patient receiving levodopa. Combined levodopa-prednisone therapy was then instituted, with good clinical response and no recurrence of thrombocytopenia.     

The current status of adjuvant hormonal therapy combined with radiation therapy for localised prostate cancer

The limbic system comprises the hippocampal formation, fornix, mamillary bodies, thalamus, and other integrated structures. It is involved in complex functions including memory and emotion and in diseases such as temporal lobe epilepsy. Volume measurements of the amygdala and hippocampus have been used reliably to study patients with temporal lobe epilepsy but have not extended to other limbic structures. We performed volume measurements of hippocampus, amygdala, fornix and mamillary bodies in healthy individuals. Measurements of the amygdala, hippocampus, fornix and mamillary bodies revealed significant differences in volume between right and left sides (P < 0.001). The intraclass coefficient of variation for measurements was high for all structures except the mamillary bodies. Qualitative image assessment of the same structures revealed no asymmetries between the hemispheres. This technique can be applied to the study of disorders affecting the limbic system.     

Stevens-Johnson syndrome associated with carvedilol therapy

Stevens-Johnson syndrome, related to carvedilol use, has not been previously reported as a serious adverse experience requiring hospitalization. We report this reaction in a 71-year-old man with stable ischemic cardiomyopathy.     

A randomized trial of long term adjuvant tamoxifen plus postoperative radiation therapy versus radiation therapy alone for patients with early stage breast carcinoma treated with breast-conserving surgery. Stockholm Breast Cancer Study Group

BACKGROUND: The use of adjuvant tamoxifen to treat postmenopausal breast carcinoma patients as an adjunct to primary surgery is well established. The current study reports the long term results for a low risk stratum in a randomized trial of adjuvant tamoxifen. The main focus of this analysis was to determine whether tamoxifen would result in a reduced local failure rate for lymph node negative, postmenopausal patients treated with breast-conserving surgery and postoperative radiotherapy. METHODS: The study population included 432 lymph node negative, postmenopausal patients with invasive breast carcinoma (classified as T1-T2) who underwent breast-conserving surgery followed by radiotherapy in Stockholm during the period 1976-1990. The patients constituted a separate stratum of the Stockholm Adjuvant Tamoxifen Trial, which included a total of 2729 patients. Of 432 patients, 213 received 40 mg of tamoxifen daily for either 2 or 5 years. The median follow-up time was 8 years (range, 5-19 years). RESULTS: At 10 years, the overall survival was 90% for the tamoxifen group and 88% for the control group. The event free survival at 10 years was 80% for the tamoxifen group and 70% for the control group (P=0.03). Tamoxifen reduced the overall rate of ipsilateral (hazard ratio=0.4, 95% confidence interval [CI]=0.2-0.9, P=0.02) and contralateral breast tumor recurrences (hazard ratio=0.4, 95% CI=0.1-1.1, P=0.06). Trends toward a reduced number of distant metastases (hazard ratio=0.6, 95% CI=0.3-1.2, P=0.1) and deaths due to breast carcinoma (hazard ratio=0.5, 95% CI=0.2-1.2, P=0.1) also were observed. CONCLUSIONS. The addition of tamoxifen to radiotherapy for postmenopausal, lymph node negative breast carcinoma patients treated with breast-conserving surgery resulted in a reduced rate of ipsilateral and contralateral breast tumor recurrences. The avoidance of salvage mastectomies, reexcisions, and new contralateral malignancies justifies the use of tamoxifen even in the treatment of patients with a 10-year survival rate of 90%.