Impact of adjuvant systemic chemotherapy on postoperative survival in patients with high-risk urothelial cancer

BACKGROUND: The objective of this study was to retrospectively investigate the effectiveness of adjuvant combination chemotherapy for locally advanced urothelial cancer. METHODS: Between 1987 and 1998, 56 patients with locally advanced bladder (n = 27) or upper urinary tract (n = 29) cancer (pathological stage T3, T4 or N1, N2 and M0) were treated by radical cystectomy or radical nephroureterectomy and regional lymphadenectomy. Thirty-one patients had lymph node-positive disease and 25 patients did not. Twenty patients underwent adjuvant chemotherapy and 36 patients were observed after surgery. Cox proportional hazards models were used to determine the impact of numerous clinicopathological findings on survival. A subgroup analysis of patients with lymph node-positive disease was conducted to evaluate disease-free survival and overall survival rates. RESULTS: In this series, the median follow-up period was 39 months (range, 4-163) after surgery. Disease-free and overall survival rates of all 56 patients were 45% and 58%, respectively, at 3 years. Only lymph node status was significantly associated with disease-free and overall survival in the multivariate analyses. In a subgroup analysis of patients with lymph node-positive disease, 16 patients who underwent adjuvant chemotherapy had superior disease-free survival compared to 15 patients with no adjuvant chemotherapy (P = 0.0376). CONCLUSION: These findings show that the prognosis of advanced urothelial cancer is significantly associated with nodal status. Furthermore, adjuvant combination chemotherapy has a positive impact on survival in patients with lymph node-positive disease.     

Gastrointestinal manometry findings in a case with dilated small bowel and disturbed transit treated successfully with bowel plication

Abstract We report the manometric findings in a case of dilated small bowel and disturbed transit successfully treated with plication of the dilated small bowel. The female newborn infant required total parenteral nutrition following an operation for small bowel atresia. X-ray showed a dilated proximal small bowel. Jejunal manometry showed normal phase 3 migration but persistently low-amplitude contractions in the dilated segment. After plication of the dilated intestine, symptoms of bowel obstruction disappeared. A second manometry two weeks after the operation showed contractions with normal amplitude. These findings indicate that: (1) disturbed transit in the dilated intestine proximal to small intestinal atresia is associated with persistently low contraction amplitude, and (2) the amplitude can be increased by the plication of the dilated loop.     

Adverse drug reactions of intravesical bacillus Calmette–Guérin instillation and risk factors of the development of adverse drug reactions in superficial cancer and carcinoma in situ of the bladder

BACKGROUND: We examined the incidence and severity of adverse drug reactions following intravesical bacillus Calmette-Guerin (BCG) instillation for superficial bladder cancer including carcinoma in situ. We investigated the relationship between adverse drug reactions and patient background to clarify risk factors for the development of adverse drug reactions. METHODS: A total of 123 patients who underwent intravesical BCG instillation for treatment and prophylaxis between April 1997 and June 2000 were included in this study. Adverse drug reactions were divided into local and systemic categories and the severity of reactions was classified according to the presence or absence of postponement or discontinuation of instillation, with or without treatment for the reaction itself. RESULTS: Of 123 patients, 95.9% showed adverse drug effects and 50.4% needed some sort of treatment. Discontinuation of instillation due to adverse drug reactions was observed in nine patients. Regarding the necessity of treatment for adverse drug effects, the purpose of instillation and BCG dose were independent significant factors on multivariate analysis. CONCLUSION: Although there was a high rate of adverse drug reactions after intravesical BCG instillation, the rate of discontinuation of instillation was not high and serious adverse reactions were rare. The scale of the present study was small, but these results suggest that BCG instillation was well tolerated. When instillation is being performed for the purpose of treatment, and the BCG dose is 80 mg, greater attention might be needed to monitor for the development of adverse drug effects.     

Systemic Toxicity of the Heavy Fraction of a Coal Coprocessing Product in Male Rats Following Subchronic Dermal Exposure

The systemic toxicity of a coal coprocessing product [heavygas oil II (HGOII)] following subchronic, dermal exposure inmale Sprague-Dawley rats was investigated. HGOII was appliedto the dorsal skin daily at doses of 8.7, 20.8, 50.0, or 120.0mg/ kg body weight (bw) for 13 weeks. Another group of ratstreated with a medium boiling coal liquefaction product (CLP)served as positive controls. Growth suppression and decreasedfood consumption were noted in the groups exposed to HGOII at20.8 mg/kg and higher, and to CLP starting at the third weekof treatment. Relative liver, kidney, and brain weights in the20.8 mg/kg HGOII group and up were higher than those of thecontrol. Increased spleen weight was observed in all HGOII-treatedgroups. CLP treatment also caused increased relative kidneyand brain weights. Serum cholesterol was elevated in the HGOII-treatedgroups starting at 8.7 mg/kg while increased uric acid and lactatedehydrogenase were observed at 20.8 mg/kg and up. Decreasederythrocyte, hemoglobin, and platelet counts were observed at20.8 mg/kg and higher. All HGOII-treated groups had elevatedreticulocytes. These biochemical and hematological changes werenot observed in the CLP-treated group. Mild to marked histologicalchanges were observed in the thyroid, thymus, liver, spleen,and bone marrow of HGOII groups. In contrast, morphologicalchanges were relatively mild in CLP-treated animals. Data fromthe present study demonstrated that the hematological endpointswere sensitive to the liquid fuels and that HGOII was more toxicthan CLP. Based on the growth rate and biochemical, hematological,and morphological changes, the no observable adverse effectlevel for HGOII is judged to be below 8.7 mg/kg bw in the rat.     

Mechanism for Species-Specific Induction of Leydig Cell Tumors in Rats by Lansoprazole

Lansoprazole is a substituted benzimidazole which inhibits gastricacid secretion by inhibiting the hydrogen-potassium ATPase (protonpump) in the parietal cell. The finding of Leydig cell hyperplasiaand Leydig cell tumors in 2-year oral studies in Sprague-Dawleyrats but not in CD-1 mice prompted investigative studies todetermine the mechanism for the Leydig cell changes. hCG challengestudies in Sprague-Dawley rats revealed decreased testosteroneresponsiveness in rats treated orally for 1 or 2 weeks withlansoprazole. After 4 weeks of daily oral treatment increasesin serum LH and decreases in serum testosterone were detectedwithin a few hours after dosing. In a study where 9-month-oldmale F344 rats were given testosterone supplementation via Silasticimplants and then treated with lansoprazole for 6 months, ahigh incidence of Leydig cell tumors was seen in lansoprazoletreated,unsupplemented rats, whereas no Leydig cell tumors were seenin testosterone supplemented rats. This implied that reductionof the normal feedback inhibition at the level of the hypothalaumsand/or pituitary due to reduced testosterone levels, thus givingrise to elevated levels of LH, was involved in the inductionof Leydig cell tumors by lansoprazole. In vitro studies withLeydig cells from rats using various stimulators and precursorsof testosterone biosynthesis demonstrated that the most sensitivesite for inhibition of testosterone synthesis by lansoprazoleis the transport of cholesterol to the cholesterol side chaincleavage enzyme. The IC50s for inhibition of LH or hCG-stimulatedtestosterone synthesis in Leydig cells from rats, mice, andmonkeys were 11–12, 8, and 27.4 µg/ml, respectively.In vitro studies with metabolites of lansoprazole revealed thatthree metabolites were more potent inhibitors of testosteronesynthesis than the parent drug, two of them being at least 10times more potent. These metabolites are present in rats atsubstantial levels but are undetectable in humans. The lackof induction of Leydig cell tumors in mice, lower sensitivityof primate Leydig cells, and the absence of testosterone synthesisinhibitingmetabolites in man suggest that Leydig cell tumors found inrats represent a species-specific sensitivity and does not implya risk for clinical use in man.     

Dystrophin negative skeletal and myocardial muscle cells in a carrier of Duchenne's muscular dystrophy

A 47-year-old woman whose elder son had typical Duchenne's musculardystrophy (DMD) was diagnosed as the manifesting carrier ofthe disease. She had developed congestive heart failure buthad no evidence of skeletal muscular atrophy. Histological observationof the cardiac muscle revealed a mosaic pattern of dystrophinnegative fibres detected by immunofluorescence analysis.