Risk of pancreatic cancer and occupational exposures in Spain. PANKRAS II Study Group

The objective of the study was to analyse the relationship between occupational exposures and risk of pancreatic cancer. Incident cases of pancreatic cancer and hospital controls were prospectively identified and interviewed during the hospital stay. Occupational history was obtained by direct interview with the patient, and was available for 164 (89%) of 185 pancreatic cancer cases, and 238 (90%) of 264 controls. Two industrial hygienists evaluated exposures to 22 suspected carcinogens previously associated with pancreatic cancer. Occupational exposures were also assessed using the Finnish job-exposure matrix (FINJEM). For each type of pesticide group, moderately increased odds ratios (OR) were apparent in the high-intensity category, highest for arsenical pesticides (OR=3.4; 95% CI 0.9-12.0), and 'other pesticides' (OR=3.17; 95% CI 1.1-9.2). ORs for aniline derivatives, and dyes and organic pigments, were also higher for high-intensity exposure, and increased when lagged and restricted to long duration of exposure. ORs above 3 were observed for the following agents evaluated by FINJEM: pesticides, benzo[a]pyrene, lead, volatile sulphur compounds, and sedentary work. Whilst generally negative, results lend moderate support to the hypothesis of an association between exposure to some pesticides and pancreatic cancer. Larger studies could address the potential for these compounds to modify the carcinogenic risk of other environmental exposures. Suggestive increases in risk from aniline derivatives, dyes and organic pigments, and benzo[a]pyrene may also deserve further attention.     

Synapsis and meiotic recombination analyses: MLH1 focus in the XY pair as an indicator

BACKGROUND: Anomalies in meiotic prophase I have been related to partial or total meiotic arrest. These anomalies include an abnormal synaptic process, resulting in disorders in meiotic recombination. METHODS: In the present study, we analyse primary spermatocytes from 12 infertile men (four with non-obstructive azoospermia, six with oligoastenoteratozoospermia, one with astenoteratozoospermia and one normozoospermic) and five control fertile donors using immunocytological techniques for synaptonemal complex, meiotic recombination and centromeric proteins. RESULTS: Mean numbers of MLH1 foci per cell, frequencies of cells presenting an MLH1 focus in the XY pair and percentages of cells affected by abnormal synaptic patterns (gaps and splits) are reported for each of the infertile patients and control men. A positive correlation between the frequency of cells showing a recombination focus in the XY pair and the number of autosomal recombination foci per cell is found. CONCLUSIONS: Reduced recombination in the XY pair and an increased number of cells affected by gaps may explain some idiopathic male infertility cases. The results suggest that recombination in the XY pair could be an indicator for general recombination frequency and for a successful meiotic process.     

Karyotyping of human synaptonemal complexes by cenM-FISH

The purpose of this work was to adapt the recently described centromere-specific multicolour (cenM-) FISH technique to human meiotic cells, and evaluate the usefulness of this multiplex fluorescence method for karyotyping human synaptonemal complex (SC), previously analysed by immunocytogenetic approaches. The results obtained demonstrate that cenM-FISH is a reliable one-single-step method, which allows for the identification of all SC present in pachytene spreads. Moreover, when cenM-FISH is applied after immunocytogenetic analysis, the number and distribution of MLH1 foci per chromosome can be established and recombination analysis for each chromosome can be performed easily.     

Endothelial cell chimerism does not influence allograft tolerance in liver transplant patients after withdrawal of immunosuppression

BACKGROUND: Human liver allografts sometimes show self-induced permanent tolerance without immunosuppression. It has recently been proposed that the replacement of liver donor endothelial cells by recipient cells could confer a survival advantage. The aim of this study was to analyze liver endothelial cell replacement in relation to the response (tolerance or rejection) after withdrawal of immunosuppression in liver transplant patients. METHODS: Nine liver recipient patients were entered into a program of immunosuppressive drug withdrawal. The authors studied liver endothelial cell chimerism in five of these patients who received a liver from a donor of the opposite sex by in situ hybridization for X and Y chromosomes. RESULTS: Three patients (33%) achieved complete withdrawal of immunosuppression. The authors' data show similar endothelial cell chimerism in both the tolerant and nontolerant patients analyzed. CONCLUSIONS: Endothelial cell chimerism has nothing to do with the induction of clinical tolerance in liver transplant patients after withdrawal of immunosuppression.     

Sorafenib in metastatic thyroid cancer

Although thyroid cancer usually has an excellent prognosis, few therapeutic options are available in the refractory setting. Based on the recent results of phase II studies with tyrosine kinase inhibitors, we designed a retrospective analysis of patients with metastatic thyroid cancer treated with sorafenib in seven Spanish referral centers. Consecutive patients with progressive metastatic thyroid cancer (papillary, follicular, medullary, and anaplastic) not suitable for curative surgery, radioactive-iodine therapy, or radiotherapy were treated with sorafenib 400 mg twice a day. The primary end point was objective response rate (RR). Secondary end points included toxicity, median progression-free survival (mPFS), median overall survival (mOS), and correlation between tumor marker levels (thyroglobulin, calcitonin, and carcinoembryonic antigen) and efficacy. Between June 2006 and January 2010, 34 patients were included in the study. Sixteen patients presented differentiated thyroid carcinomas (DTC) of which seven (21%) were papillary, nine (26%) follicular, 15 (44%) medullary (MTC), and three (9%) were anaplastic (ATC). Eleven (32%) patients achieved partial response and 14 (41%) had stable disease beyond 6 months. Regarding histological subtype, RRs were 47% (seven of 15) for MTC, 19% (three of 16) for DTC, and 33% (one of three) for ATC. With a median follow-up of 11.5 months, mPFS were 13.5, 10.5, and 4.4 months for DTC, MTC, and ATC respectively. Tumor markers were evaluated in 22 patients, and a statistically significant association was observed between RR and decrease in tumor marker levels >50% (P=0.033). In this retrospective trial, sorafenib showed antitumor efficacy in all histological subtypes of thyroid cancer, warranting further development in this setting.