Gemcitabine plus cisplatin for advanced transitional cell carcinoma of the urinary tract: a phase II multicenter trial

PURPOSE: We determined the activity and toxicity of gemcitabine plus cisplatin in patients with inoperable or metastatic transitional cell carcinoma of the urinary tract. MATERIALS AND METHODS: A total of 54 patients with transitional cell carcinoma, measurable disease and Eastern Cooperative Oncology Group performance status 2 or greater were enrolled in this multicenter phase II trial. Previous adjuvant or neoadjuvant therapy for locally advanced disease was acceptable if it had been completed more than 1 year before study entry. Every 4 weeks patients received 1,000 mg./m.2 gemcitabine intravenously on days 1, 8 and 15, and 70 mg./m.2 cisplatin intravenously on day 2. RESULTS: All patients were evaluable for response and toxicity. Notably only 7 of the 54 patients (13%) previously received chemotherapy in an adjuvant or neoadjuvant setting. Overall we observed 26 objective responses (48%), of which 15% were complete. Median time to progression was 23 weeks and median survival was 54 weeks. Treatment was well tolerated. The main toxicities were leukopenia (grade 3 in 28% and grade 4 in 11% of patients), anemia (grade 3 in 34% and grade 4 in 6%) and thrombocytopenia (grade 3 in 14% and grade 4 in 6%). Other relevant side effects were nausea and vomiting in 20% of cases, fever in 24%, alopecia in 22%, renal failure in 7.4% and mucositis in 2%. CONCLUSIONS: Combined cisplatin plus gemcitabine is highly active in advanced transitional cell carcinoma of the urinary tract with manageable toxicity. The response rate, time to treatment failure and overall survival appeared to be comparable to those achieved with combined methotrexate, vinblastine, doxorubicin and cisplatin. Conversely toxicity appeared lower. Evaluation of this regimen in randomized studies with methotrexate, vinblastine, doxorubicin and cisplatin is strongly suggested.     

Two-stage versus one-stage sex reassignment surgery in female-to-male transsexual individuals

The objective was to compare the outcome of a combined total hysterectomy-vaginectomy-phalloplasty procedure vs. a vaginectomy-phalloplasty procedure in female-to-male (FTM) gender dysphoric individuals, and to report on a large series of vaginectomies in young women. This was a retrospective study and the setting was the Gender Team at Ghent University Hospital. One hundred and five consecutive cases of vaginectomy-phalloplasty with (one-stage) or without (two-stage) total hysterectomy between 1993 and 2003 were included in the study. Patient files of 69 one-stage and of 36 two-stage procedures were reviewed and analysed. Operation time, the need for transfusions, complications, repeated surgery and hospitalisation time were the main outcome measures. Patients were equally distributed over the study period of 10 years. Comparing the two groups, there was a greater need for transfusion in the group of patients undergoing the one-stage procedure. There was no difference in operation time, rate of major complications or hospitalisation time. One-stage sex reassignment surgery (SRS) in FTM transsexual individuals is associated with more blood loss. However, there is no difference in operative and postoperative complications. Vaginectomy seems to be a safe and relatively simple procedure in FTM transsexual patients.     

Evaluation of tamoxifen and anastrozole in the prevention of gynecomastia and breast pain induced by bicalutamide monotherapy of prostate cancer.

PURPOSE: To determine whether tamoxifen or anastrozole prevents gynecomastia and breast pain caused by bicalutamide (150 mg) without compromising efficacy, safety, or sexual functioning. PATIENTS AND METHODS: A double-blind, placebo-controlled trial was performed in patients with localized, locally advanced, or biochemically recurrent prostate cancer. Patients (N = 114) were randomly assigned to either bicalutamide (150 mg/d) plus placebo or in combination with tamoxifen (20 mg/d) or anastrozole (1 mg/d) for 48 weeks. Gynecomastia, breast pain, prostate-specific antigen (PSA), sexual functioning, and serum levels of hormones were assessed. RESULTS: Gynecomastia developed in 73% of patients in the bicalutamide group, 10% of patients in the bicalutamide-tamoxifen group, and 51% of patients in the bicalutamide-anastrozole group (P < .001); breast pain developed in 39%, 6%, and 27% of patients, respectively (P = .006). Baseline PSA level decreased by > or = 50% in 97%, 97%, and 83% of patients in the bicalutamide, bicalutamide-tamoxifen, and bicalutamide-anastrozole groups, respectively (P = .07); and adverse events were reported in 37%, 35%, and 69% of patients, respectively (P = .004). There were no major differences among treatments in sexual functioning parameters from baseline to month 6. Elevated testosterone levels occurred in each group; however, free testosterone levels remained unchanged in the bicalutamide-tamoxifen group because of increased sex hormone-binding globulin levels. CONCLUSION: Anastrozole did not significantly reduce the incidence of bicalutamide-induced gynecomastia and breast pain. In contrast, tamoxifen was effective, without increasing adverse events, at least in the short-term follow-up. These data support the need for a larger study to determine any effect on mortality.     

Are preoperative parameters of unilateral pyelo-ureteric junction obstruction in children predictive of postoperative function improvement?

OBJECTIVES: Surgery on the pyelo-ureteric junction obstruction (PUJO) has long been thought to affect postoperative renal function. However, preoperative assessment of which kidneys will benefit from such surgery remains unreliable. MATERIAL AND METHODS: Pre- and postoperative data relating to renal function were obtained by renal scan for 69 patients who were operated upon for PUJO. These patients were divided into two groups: group A (improved differential renal function) and group B (unimproved or decreased differential renal function). The two groups were then compared with regard to age at operation and presence or absence of clinical symptoms. Ultrasound (anteroposterior diameter of the pelvis, parenchymal thickness) and renal scan (glomerular filtration rate, differential renal function of the affected kidney, obstructive pattern) parameters were also taken into consideration. Some variables were also made dichotomous (pelvic diameter < or > 15 mm, parenchymal thickness < or > 5 mm, differential renal function < or > 40%). Statistical correlation was sought with parametric and non-parametric tests. RESULTS: No correlation whatsoever was found between the two groups for any of the parameters under consideration, so that any attempt at logistical regression analysis failed. CONCLUSIONS: None of the currently adopted diagnostic tests can be used to indicate which renal units will benefit from surgery through an improved renal function. The presence or absence of clinical symptoms does not appear to affect renal function either. There is evidence that parents should be provided with such information when giving their informed consent to pyeloplasty.     

Differential diagnosis of pulmonary embolism in outpatients with non-specific cardiopulmonary symptoms

Most cardiopulmonary diseases share at least one symptom with pulmonary embolism (PE). The aim of this study was to identify the most common acute causes of dyspnea, chest pain, fainting or palpitations, which diagnostic procedures were performed and whether clinicians investigate them appropriately. An Italian multicenter collaboration gathered 17,497 Emergency Department (ED) records of patients admitted from January 2007 to June 2007 in six hospitals. A block random sampling procedure was applied to select 800 hospitalised patients. Results of the overall 17,497 patients were obtained by weighting sampled cases according to the probability of the randomisation block variables in the whole population. The case-mix of enrolled patients was assessed in terms of cardiopulmonary symptoms, and the prevalence of acute disorders. The actual performance of procedures was compared with a measure of their accuracy as expected in the most common clinical presentations. PE occurred in less than 4% of patients with cardiopulmonary symptoms. Acute heart failure, pneumonia and chronic obstructive pulmonary disease exacerbation were the most likely diagnoses in patients with dyspnea. Acute myocardial infarction was present in roughly 10% of patients with chest pain. Atrial fibrillation was the prevalent diagnosis in patients with palpitations. Echocardiography, computed tomographic pulmonary angiography, perfusion lung scan, D-dimer test and B-type natriuretic peptide were performed less than expected from their accuracy. Diagnostic strategies, starting from non-specific symptoms and coping with the eventuality of PE, are likely to benefit from an increased awareness of the examination’s accuracy in discriminating among several competing hypotheses, rather than in testing the single PE suspicion.     

Thiotepa‐based versus total body irradiation‐based myeloablative conditioning prior to allogeneic stem cell transplantation for acute myeloid leukaemia in first complete remission: a retrospective analysis from the Acute Leukemia Working Party of the European Group for Blood and Marrow Transplantation

Thiotepa is an alkylating compound with an antineoplastic and myeloablative activity and can mimic the effect of radiation. However, it is unknown whether this new regimen could safely replace the long‐established ones. This retrospective matched‐pair analysis evaluated the outcome of adults with acute myeloid leukaemia in first complete remission who received myeloablative conditioning either with a thiotepa‐based (n = 121) or a cyclophosphamide/total body irradiation‐based (TBI; n = 358) regimen for allogeneic hematopoietic stem cell transplantation from an HLA‐matched sibling or an unrelated donor. With a median follow‐up of 44 months, the outcome was similar in both groups. Acute graft‐versus‐host disease grade II‐IV was observed in 25% after thiotepa‐containing regimen versus 35% after TBI (P = 0.06). The 2‐yr cumulative incidence of chronic graft‐versus‐host disease was 40.5% for thiotepa and 41% for TBI (P = 0.98). At 2 yrs, the cumulative incidences of non‐relapse mortality and relapse incidence were 23.9% (thiotepa) vs. 22.4% (TBI; P = 0.66) and 17.2% (thiotepa) vs. 23.3% (TBI; P = 0.77), respectively. The probabilities of leukaemia‐free and overall survival at 2 yrs were not significantly different between the thiotepa and TBI groups, at 58.9% vs. 54.2% (P = 0.95) and 61.4% vs. 58% (P = 0.72), respectively. Myeloablative regimens using combinations including thiotepa can provide satisfactory outcomes, but the optimal conditioning remains unclear for the individual patient in this setting.