Predictors of long-term survival in patients with gallbladder cancer

The aim of this study was to examine the predictors of long-term survival (>24 months) in patients with gall bladder cancer. A retrospective review of 117 cases of gall bladder cancer resected between 1989 and 2000. The resections included 80 simple cholecystectomies and 37 extended procedures. Patients with survival >24 months (n=44) were compared with those having survival <24 months (n=73) for 17 prognostic factors. Overall median survival was 16 months with a 5-year survival of 27%. T status (P=.000) and adjuvant chemoradiotherapy (P=.001) were independent predictors of long-term survival. Survival advantage was seen in T3N+ve disease (P=.007) with extended procedures. Complete (R0) resection was attained in 30 patients with a 5-year survival advantage of 30% as compared with incomplete (R1) resection (P=.0002). Adjuvant chemoradiotherapy improved survival in simple cholecystectomy group (P=.0008) but no advantage was seen after extended procedures. Stage III (P=.001) and node-positive disease (P=.0005) had significant benefit with adjuvant therapy. Poor differentiation and vascular invasion were associated with poor long-term survival. R0 resection was associated with prolonged survival. Extended procedures improved survival in patients with T3N+ve disease. Addition of chemoradiotherapy made significant improvement in long-term survival in stage III and node-positive lesions and in patients undergoing simple cholecystectomy. R0 resection predicted long-term survival in gall bladder cancer. T3 N+ve disease had better survival after extended procedures. Adjuvant chemoradiotherapy improved survival in stage III and node-positive disease. Poor differentiation and vascular invasion were adverse predictors of survival.     

Return of fertility following discontinuation of an injectable contraceptive — Norethisterone oenanthate (NET EN) 200mg dose

The return of fertility following discontinuation of norethisterone oenanthate (NET EN) 200 mg injectable contraceptive after use for a minimum period of six months or more was studied in 69 women who discontinued the method for planning pregnancy. Former users of copper intra-uterine device (CuT 200) were enrolled as a control group. Another 161 women who had discontinued NET EN due to other reasons (e.g. amenorrhoea, excessive bleeding or personal reasons) were also studied for return of fertility after ensuring that they were not using any other method of contraception and were exposed to the risk of pregnancy. The subjects from both groups were followed for a period of one year. The cumulative conception rates at one year were 72.5 and 83.6 per 100 subjects for ex-NET EN and ex-CuT 200 users who had discontinued the method for planning pregnancy and this difference was not statistically significant (P > 0.05). The median time for conception for ex-NET EN users was 7.8 months as compared to 3.7 months in ex-CuT 200 users but the cumulative conception rates at the end of one year show that future return of fertility in NET EN users does not appear to be adversely affected.

In 51 subjects who had discontinued NET EN due to amenorrhoea, the return of fertility was predictably slower and less. The return of fertility in subjects who discontinued NET EN for other reasons (e.g. excessive bleeding and other personal reasons) was similar to ex-NET EN and ex-CuT 200 users.     

Complex urethral disruptions: In pursuit of a successful reconstruction

OBJECTIVES: We analyzed the methods and outcomes of urethroplasty in men with complex urethral disruptions. METHODS: The medical records of 40 men with complex urethral disruptions were analyzed. Surgical methods were individualized according to stricture location, severity and length of the stricture, bladder neck characteristics and presence of complicating factors. Patients were divided into four groups based on the above characteristics. RESULTS: End-to-end urethroplasty performed in six patients with short bulbar strictures (<3 cm) was successful in all. Elaborated perineal repair was performed in 10 patients with intermediate (3-6 cm) strictures with or without complicating factors. Elaborated perineal repair with urethral substitution was performed in nine patients with long segment stricture (>6 cm). Abdominal transpubic repair was successfully applied to patients with rectourethral fistula or lacerated bladder neck. Success rate of anastomotic urethroplasty was 95% while over all success rate was 85%. CONCLUSION: Guidelines for urethral reconstruction of complex urethral disruptions are predicated on stricture length, location, bladder neck characteristics and associated complicating factors. End-to-end urethroplasty with stricture excision is highly reliable for short strictures for which previous operative repair have failed. Elaborated perineal repair is extremely versatile for intermediate and longer strictures with associated complicating factors. Abdominal transpubic urethroplasty is effective for patients with rectourethral fistula or lacerated bladder neck.     

Brca2 is coordinately regulated with Brca1 during proliferation and differentiation in mammary epithelial cells

We have analyzed the expression of the breast cancer susceptibility gene, Brca2, in mammary epithelial cells as a function of proliferation and differentiation. Our results demonstrate that Brca2 mRNA expression is tightly regulated during mammary epithelial proliferation and differentiation, and that this regulation occurs coordinately with Brca1. Specifically, Brca2 mRNA expression is up-regulated in rapidly proliferating cells; is down-regulated in response to serum deprivation; is expressed in a cell cycle-dependent manner, peaking at the G₁/S boundary; and is up-regulated in differentiating mammary epithelial cells in response to glucocorticoids. In each case, an identical pattern of expression was observed for Brca1. These results indicate that proliferative stimuli modulate the mRNA expression of these two breast cancer susceptibility genes. In addition, the coordinate regulation of Brca1 and Brca2 revealed by these experiments suggests that these genes are induced by, and may function in, overlapping regulatory pathways involved in the control of cell proliferation and differentiation.     

Poliomyelitis trends in Pondicherry, south India, 1989-91.

STUDY OBJECTIVES: To assess the poliomyelitis trend, including study of the epidemiological features, and to correlate this with the immunisation coverage of infants. DESIGN: Three annual lameness surveys in children aged 0-60 months employing cluster sampling methods and a series of five cross sectional surveys of immunisation coverage in children aged 12-23 months of age were undertaken. SETTING: Pondicherry, India, 1988-92. SUBJECTS: More than 10,000 children in the age group of 0-60 months took part in the three annual lameness surveys and samples of 210 children aged 12-23 months were covered each year in immunisation coverage surveys. MEASUREMENTS AND MAIN RESULTS: Altogether 50 of 11,461, 24 of 10,093, and 17 of 11,218 children surveyed during 1989, 1990, and 1991 respectively had become lame as a result of poliomyelitis, giving prevalences of 4.4, 2.4, and 1.5 per 1000 children for the three surveys. The corrected prevalences of poliomyelitis were 5.9, 3.2, and 2.0 per 1000 children during 1989, 1990, and 1991 respectively. The proportion of cases aged up to 36 months fell from 48% in 1989 to 12.5% in 1990 and 6% in 1991. The age at onset was less than 1 year in most. The median age at onset was 10.7 months. About 54% of the affected children had received three doses of oral poliomyelitis vaccine (OPV) before the onset of paralysis. In 1988 immunisation coverage for the third dose of OPV was 91% and in 1992 it was 97.6%. The drop out rate for the first versus the third dose of OPV fell from 6.3 in 1988 to 1.9% in 1992. CONCLUSION: Three successive annual lameness surveys showed that poliomyelitis was declining between 1989 and 1991. Five immunisation coverage surveys conducted from 1988 to 1992 showed high initial coverage followed by an improvement in the form of almost universal coverage for OPV.     

31P NMR spectroscopic study of bioenergetic changes in radiation-induced fibrosarcoma-1 after radiation therapy

The effects of localized gamma-irradiation on the in vivo 31P NMR spectra of RIF-1 tumors grown subcutaneously in C3H/HeN mice have been examined before and during the week after treatment. Increases in the ratio of phosphocreatine (PCr) to inorganic phosphate (Pi) and in tumor pH, and decreases in the ratio of Pi to the beta phosphorus resonance of the nucleotide triphosphates (beta NTP) were observed in irradiated tumors. The time course of changes in the 31P spectrum following treatment was the opposite of the pattern during untreated growth, and the magnitude and duration of the changes increased with increasing radiation dose, decreasing clonogenic cell survival and increasing growth delay. To examine the possibility that nontherapeutic systemic effects of the tumor irradiation were responsible for the changes observed, a number of animals bearing two tumors were examined. One tumor on each mouse was selectively irradiated. Changes in tumor volume, Pi/beta NTP, PCr/Pi, the ratio of phosphomonoesters to beta NTP, and tumor pH were all significantly different in the treated compared to the untreated tumor on each animal, indicating that these changes in 31P NMR spectra were a response to radiation therapy and not a systemic response to radiation toxicity.     

Modeling mechanisms of skull base injury for drivers in motor vehicle collisions.

OBJECTIVE: To develop biomechanical variable models for driver skull base injury mechanisms in motor vehicle collisions. STUDY DESIGN: Retrospective database review. METHODS: Biomechanical collision variables and safety restraint data were analyzed for Crash Injury Research and Engineering Network skull base trauma subjects enrolled during the recruitment period between 1996 and 2005. RESULTS: For drivers satisfying inclusion criteria (n = 26), injury resulted from contact with rigid vehicle structural elements in 82%, and occurred in 50% despite both seatbelt and air bags. Eight percent used neither seatbelts nor air bags. Seventy-two percent involved vector velocity changes greater than 30 mph. The relative morbidity of skull base injuries was also detailed. CONCLUSION: The majority of driver skull base injuries resulted from contact with rigid vehicle structural elements in high velocity crashes. Seatbelt and air bag use could not be definitively correlated with skull base injury. CLINICAL SIGNIFICANCE: Injury mechanism models can be developed that facilitate further investigations to determine impact and scope on a national scale.