Nonsteroidal anti-inflammatory drug use associated with reduced incidence of adenocarcinomas of the esophagus and gastric cardia that overexpress cyclin D1: a population-based study.

This study was undertaken to determine whether selected risk factors for esophageal and gastric cancer are associated with tumors that overexpress cyclin D1. Archived tumor tissue was available for 630 esophageal and gastric cancer patients who participated in a population-based case-control study. Patients were categorized into case groups based on whether protein overexpression of the cyclin D1 gene, as assessed by immunohistochemistry, was present (cyclin D1+, n = 285) or not (cyclin D1-, n = 345) in the tumor. The distribution of risk factors in each of these case groups was then compared with the distribution among the 695 controls. Multivariate-adjusted odds ratios (OR) for esophageal adenocarcinoma were reduced in relation to use of aspirin and other nonsteroidal anti-inflammatory drug (NSAID) use but only among patients with cyclin D1+ tumors (0.45, 95% confidence interval [CI] = 0.26, 0.79) and not among those with cyclin D1- tumors (1.12, 95% CI = 0.67, 1.86). A similar pattern was observed for gastric cardia adenocarcinomas. In contrast, ORs for esophageal squamous cell carcinoma and noncardia gastric adenocarcinomas in relation to NSAID use were reduced, regardless of cyclin D1 status. ORs did not vary with cyclin D1 status in relation to alcohol, body size, or cigarette smoking, with the following exception; for noncardia gastric adenocarcinomas the cyclin D1- tumors showed a 2-fold elevation in the OR with ever smoking. These data suggest that the reduction in risk associated with NSAID use may be restricted to those esophageal and gastric cardia adenocarcinomas that overexpress cyclin D1.     

Paclitaxel-induced stomal neuropathy: a unique cause of pain in a patient with ileal conduit

We present a case of unusual chemotherapy-induced neurotoxicity in a patient who had undergone radical cystoprostatectomy and ileal conduit diversion for invasive bladder cancer. On routine computed tomography scan several years later, he was diagnosed with metastatic transitional cell carcinoma involving the retroperitoneal lymph nodes. The patient received systemic chemotherapy, including a combination of paclitaxel (Taxol) and gemcitabine (Gemzar). During this treatment, the patient developed spasmodic pain and dysesthesia in the stoma area, with no apparent skin irritation or any other local finding. These symptoms resolved about 3 months after completion of the therapy.     

Gender differences in stage-adjusted bladder cancer survival

OBJECTIVES: Gender differences have been observed in the prognosis of patients with bladder cancer. It has also been suggested that these differences are caused by a worse stage distribution at diagnosis among women. The purpose of this study was to evaluate whether women with bladder cancer have a worse prognosis even after adjustment for disease stage at first presentation. METHODS: Data on patients with bladder cancer diagnosed between 1973 and 1996 and registered by one of the nine population-based Surveillance, Epidemiology, and End Results (SEER) cancer registries in the United States (n = 80,305) were obtained from the National Cancer Institute public domain SEER*Stat 2.0 package. Similar data on patients with bladder cancer diagnosed between 1987 and 1994 and registered by two population-based registries in the Netherlands (n = 1722) were obtained through the Comprehensive Cancer Centers, Amsterdam and South. Survival rates adjusted for mortality owing to other causes (ie, relative survival) were calculated for men and women within each category of the American Joint Committee on Cancer (SEER data) and TNM (Netherlands data) stage groupings.Results. In the United States, the 5-year relative survival rate of male patients with bladder cancer was calculated to be 79.5% (95% confidence interval 79.0% to 80.0%). Among women, the 5-year relative survival rate was significantly worse: 73.1% (95% confidence interval 72.2% to 74.0%). The male versus female 5-year survival rate among stage groups I, II, III, and IV was 96.5% versus 93.7%, 65.5% versus 59.6%, 58.8% versus 49.6%, and 27.1% versus 15.2%, respectively. The (sparser) data from the Netherlands were less conclusive. Women with Stage II and Stage IV disease fared worse than men but the reverse seemed to be true in Stage I disease. CONCLUSIONS: Female patients with bladder cancer have a worse prognosis than male patients. It is unlikely that the difference can explained entirely by the more frequent diagnosis of higher stages at first presentation among women.     

Assessment of the mutagenicity of dichloroacetic acid in lacI transgenic B6C3F1 mouse liver

Dichloroacetic acid (DCA) is a chlorination byproduct found in finished drinking water. When administered in drinking water this chemical has been shown to produce hepatocellular adenomas and carcinomas in B6C3F1 mice over the animal's lifetime. In this study, we investigated whether mutant frequencies were increased in mouse liver using treatment protocols that yielded significant tumor induction. DCA was administered continuously at either 1.0 or 3.5 g/l in drinking water to male transgenic B6C3F1 mice harboring the bacterial lacI gene. Groups of five or six animals were killed at 4, 10 or 60 weeks and livers removed. At both 4 and 10 weeks of treatment, there was no significant difference in mutant frequency between the treated and control animals at either dose level. At 60 weeks, mice treated with 1.0 g/l DCA showed a 1.3-fold increase in mutant frequency over concurrent controls (P = 0.05). Mice treated with 3.5 g/l DCA for 60 weeks had a 2.3-fold increase in mutant frequency over the concurrent controls (P = 0.002). The mutation spectrum recovered from mice treated with 3.5 g/l DCA for 60 weeks contained G:C-->A:T transitions (32.79%) and G:C-->T:A transversions (21.31%). In contrast, G:C-->A:T transitions comprised 53.19% of the recovered mutants among control animals. Although only 19.15% of mutations among the controls were at T:A sites, 32.79% of the mutations from DCA-treated animals were at T:A sites. This is consistent with the previous observation that the proportion of mutations at T:A sites in codon 61 of the H-ras gene was increased in DCA-induced liver tumors in B6C3F1 mice. The present study demonstrates DCA-associated mutagenicity in the mouse liver under conditions in which DCA produces hepatic tumors.      

Informed consent, parental awareness, and reasons for participating in a randomised controlled study

BACKGROUND: The informed consent procedure plays a central role in randomised controlled trials but has only been explored in a few studies on children. AIM: To assess the quality of the informed consent process in a paediatric setting. METHODS: A questionnaire was sent to parents who volunteered their child (230 children) for a randomised, double blind, placebo controlled trial of ibuprofen syrup to prevent recurrent febrile seizures. RESULTS: 181 (79%) parents responded. On average, 73% of parents were aware of the major study characteristics. A few had difficulty understanding the information provided. Major factors in parents granting approval were the contribution to clinical science (51%) and benefit to the child (32%). Sociodemographic status did not influence initial participation but west European origin of the father was associated with willingness to participate in future trials. 89% of participants felt positive about the informed consent procedure; however, 25% stated that they felt obliged to participate. Although their reasons for granting approval and their evaluation of the informed consent procedure did not differ, relatively more were hesitant about participating in future. Parents appreciated the investigator being on call 24 hours a day (38%) and the extra medical care and information provided (37%) as advantages of participation. Disadvantages were mainly the time consuming aspects and the work involved (23%). CONCLUSIONS: Parents' understanding of trial characteristics might be improved by designing less difficult informed consent forms and by the investigator giving extra attention and information to non-west European parents. Adequate measures should be taken to avoid parents feeling obliged to participate, rather than giving true informed consent.     

Dietary factors and the risk of squamous cell esophageal cancer among black and white men in the United States

Objectives: To investigate dietary factors for squamous cell esophageal cancer and whether these factors may contribute to the five-fold higher incidence of this cancer in the black versus white population of the United States.Methods: Data from a food frequency questionnaire were analyzed for 114 white men and 219 black men with squamous cell esophageal cancer, and 681 white and 557 black male controls from three areas of the United States who participated in a population-based case-control study of esophageal cancer.Results: Protective effects were associated with intake of raw fruits and vegetables (odds ratio for high versus low consumers=0.3 in both white and black men) and use of vitamin supplements (especially vitamin C; odds ratio for high versus low consumers=0.4 in both races), with the frequency of consumption of raw fruits and vegetables and vitamin supplements being greater for white than black controls. In addition, elevated risks were associated with high versus low intake of red meat (OR=2.7 for blacks and 1.5 for whites) and processed meat (OR=1.6 for blacks and 1.7 for whites), with the levels of consumption being greater for black than white controls.Conclusions: In the United States, these dietary factors may contribute in part to the much higher incidence of squamous cell esophageal cancer among black compared to white men.     

Perspectives on Pap Test Follow-Up Care Among Rural Appalachian Women

Approximately one- to three-quarters of women notified of abnormal Pap test results do not receive appropriate follow-up care, dramatically elevating their risk for invasive cervical cancer. We explored barriers to and facilitators of follow-up care for women in two counties in Appalachian Kentucky, where invasive cervical cancer incidence and mortality are significantly higher than the national average. In-depth interviews were conducted among 27 Appalachian women and seven local health department personnel. Those who had been told of an atypical Pap test result tended to have one of three reactions: (1) not alarmed and generally did not obtain follow-up care; (2) alarmed and obtained follow-up care; or (3) alarmed, but did not obtain care. Each of these typologies appeared to be shaped by a differing set of three categories of influences: personal factors; procedure/provider/system factors; and ecological/community factors. Recommendations to increase appropriate follow-up care included pursuing research on explanations for these typologies and developing tailored interventions specific to women in each of the response types.     

Implications of micropapillary urothelial carcinoma variant on prognosis following radical cystectomy: A multi-institutional investigation

Purpose

To determine the association of micropapillary urothelial carcinoma (MUC) variant histology with bladder cancer outcomes after radical cystectomy.