Introduction-Incidence rates of bladder cancer are notably higher in men than women. While there is evidence that reproductive and hormonal risk factors may influence risk of bladder cancer, data are inconclusive.Materials and Methods-We examined reproductive, menstrual and hormonal use history in our population-based case-control study of bladder cancer in New Hampshire (NH), USA (n=207 women cases and n=463 women controls). Additionally, we performed a meta-analysis of the published literature. We used unconditional logistic regression analysis to compute adjusted odds ratios associated with each risk factor in the NH study. We combined these estimates with those from the published literature using inverse variance effects models.Results-In the NH study, a slightly decreased odds ratio was found among women who had ever had a birth compared to nulliparous women and an elevated odds ratio among women who underwent surgical menopause (bilateral oophorectomy), especially at an early age. No overall associations were found with oral contraceptive use or hormone replacement therapy. These findings were generally in agreement with the meta-analytic results for which the combined RR estimate was reduced among ever parous women (combined RR estimate for ever parous versus nulliparous =0.66, 95%CI 0.55-0.79) and elevated among those undergoing an early menopause (combined RR estimate for early versus late menopause =1.59, 95%CI 1.31-1.92). No consistent risk was observed for the other factors.Discussion-Some reproductive and menstrual factors appear to be related to the incidence of bladder cancer among women; but whether effects are due to female hormones is uncertain.

BACKGROUND: Use of immunosuppressive drugs post organ transplantation, and prolonged use of glucorticoids for other conditions have been associated with subsequent risk of certain malignancies, that is, skin cancers and lymphoma. There is evidence that the incidence of bladder cancer is also elevated among organ transplant recipients, however, it is unknown whether other groups of patients, that is, those taking oral glucocorticoids, likewise are at an increased risk. METHODS: In a population-based case -control study in New Hampshire, USA, we compared the use of glucocorticoids in 786 bladder cancer cases and in 1083 controls. We used unconditional logistic regression analysis to compute adjusted odds ratios (ORs) associated with oral glucocorticoid use. RESULTS: In our analysis, the risk of bladder cancer was related to a history of prolonged oral glucocorticoid use (OR ¼ 1.85, 95% CI ¼ 1.24 -2.76, adjusted for age, gender and smoking). Associations with oral glucocorticoid use were stronger for invasive tumours (OR ¼ 2.12, 95% CI ¼ 1.17 -3.85) and tumours with high (3 þ ) p53 staining intensity (OR ¼ 2.35, 95% CI ¼ 1.26 -4.36). CONCLUSION: Our results raise the possibility of an increased risk of bladder cancer from systemic use of glucocorticoids, and a potential role of immune surveillance in bladder cancer aetiology.

Adjacent ductal carcinoma in situ (DCIS) is found in approximately 45% of invasive ductal carcinomas (IDC) of the breast. Pure DCIS overexpresses HER2 in approximately 45%. There is uncertainty whether adjacent DCIS impacts on the response to neoadjuvant chemotherapy and trastuzumab as well as whether HER2 expression in IDC component or adjacent DCIS changes throughout treatment. Core biopsies and surgical tissue from participants of the GeparQuattro study with HER2-positive IDC were centrally examined for the area of invasive ductal component and adjacent DCIS before and after receiving neoadjuvant anthracycline-taxane-trastuzumab containing chemotherapy. HER2 overexpression in IDC and adjacent DCIS was quantified separately by immunohistochemistry using the Ventana automated staining system. Pathological complete response (pCR) was defined as no residual invasive or non-invasive tumor tissue. Fifty-nine (37.3%) of 158 IDCs presented with adjacent DCIS at diagnosis. These tumors showed lower regression grades than pure IDC (P = 0.033). The presence of adjacent DCIS was an independent negative predictor of pCR [odds ratio 0.42 (95% CI 0.2-0.9), P = 0.027]. Adjacent DCIS area decreased from pre-treatment to surgery (r = 0.205) with 30 (50.8%) IDCs with adjacent DCIS showing complete eradication of adjacent DCIS. HER2 status of adjacent DCIS was highly correlated with HER2 status of IDC component before (r = 0.892) and after treatment (r = 0.676). Degree of HER2 overexpression of the IDC component decreased in 16 (33.3%) out of 49 patients without a pCR. These 16 IDCs showed lower RGs compared to the 33 IDCs with unchanged HER2 expression (P = 0.055). HER2-positive IDCs with adjacent DCIS is less responsive to neoadjuvant chemotherapy and trastuzumab compared to pure IDC. However, complete eradication of adjacent DCIS is frequently observed. HER2-overexpression of the invasive ductal component decreases in a subset of tumors, which showed less tumor regression.

Aim: To compare the efficacy and tolerability of pantoprazole 20 mg once daily (o.d.) with misoprostol 200 µg twice daily (b.i.d.), administered for 6 months to rheumatic patients who required long-term therapy with nonsteroidal anti-inflammatory drugs (NSAIDs) and who were at increased risk of developing gastrointestinal lesions. Methods: This randomized, double-blind, multicenter, parallel group comparison study was performed with rheumatic patients (n = 515) who were likely to take NSAIDs continuously for at least 6 months. Patients were 55 years or older, at risk to develop gastrointestinal lesions, had less than five erosions/petechiae in the stomach and duodenum, no ulcers, no reflux esophagitis (endoscopy-proven), and gastrointestinal symptoms of at most moderate intensity. A minimum daily dose was defined for NSAIDs (COX-2 inhibitors were not available at the time). Patients were randomized to take either pantoprazole 20 mg o.d. (n = 257) or misoprostol 200 µg b.i.d. (n = 258) for 6 months while continuing NSAID therapy. Endoscopy was performed at baseline, 3, and 6 months. Results: Pantoprazole was superior to misoprostol (p < 0.001) with regard to ‘therapeutic failure’ (occurrence of a peptic ulcer, ten or more erosions/petechiae in the stomach/duodenum, reflux esophagitis, severe gastrointestinal symptoms, and/or ‘likely’ or ‘definitely’ related adverse event leading to study termination). Estimated remission rates at 3 and 6 months (Kaplan-Meier life-table analysis) were, respectively, 93 and 89% (pantoprazole) and 79 and 70% (misoprostol). Pantoprazole was superior to misoprostol (p = 0.005) with regard to ‘endoscopic failure’ (occurrence of a peptic ulcer, ten or more erosions/petechiae in the stomach/duodenum, or reflux esophagitis) after 6 months. Estimated remission rates at 3 and 6 months were, respectively, 98 and 95% (pantoprazole) and 95 and 86% (misoprostol). Patients discontinuing the study early due to adverse events ‘likely’ or ‘definitely’ related to the study drug accounted for 13/257 (5%) in the pantoprazole and 33/258 (13%) in the misoprostol treatment groups. Conclusion: Pantoprazole 20 mg o.d. is superior to misoprostol 200 µg b.i.d. in the prevention of NSAID-induced gastrointestinal lesions and symptoms in patients on continuous long-term treatment with NSAIDs due to rheumatic diseases and at risk to develop such lesions or symptoms.

Summary Heparin‐induced thrombocytopenia (HIT) is an adverse immune‐mediated drug reaction in which antibodies are generated usually towards complexes of the soluble platelet protein platelet‐factor‐4 (PF4) and heparin. The resulting immune complexes activate platelets intravascularly, which increases the generation of thrombin. Therefore, HIT is strongly associated with thrombosis and heparin is thought to be contraindicated. As HIT antibodies decline rapidly in titre, short‐term re‐exposure to heparin is feasible in special situations. We report an uneventful liver transplantation of a heparinized donor in a patient with a 20‐month history of HIT. Before, 2, 5, 12 and 25 days after transplantation, the patient's blood was drawn for analysis of heparin‐induced antibodies by a functional assay (HIPA) and by an antigen assay (PF4‐heparin/ELISA). Lepirudin was used for postoperative anticoagulation. Apart from hepatic artery bleeding, the clinical course was uncomplicated, neither thrombocytopenia nor thromboembolic complications occurred. Weak heparin‐induced platelet activation, caused by pre‐existing HIT antibodies was detected before and 12 days after transplantation by the HIPA test; moreover borderline amounts of anti‐PF4–heparin antibodies were found. Twenty months after an episode of HIT, a patient may receive an organ from a heparin‐treated donor without risk of thrombocytopenia or thromboembolic complications. Avoidance of heparin for postoperative anticoagulation is recommended.