Histology of genital tract and breast tissue after long-term testosterone administration in a female-to-male transsexual population.

Growing evidence indicates that androgens play a positive role in follicle proliferation and growth. Hence, many authors have assumed that androgen supplementation in women with poor ovarian reserve might improve the number of antral follicles available for ovarian stimulation. As androgen administration may become more frequently used in reproductive medicine, this study aimed at describing the histological changes observed in the genital tract and the breast of female-to-male (FTM) transsexuals. A pathological analysis of the genital tract of 112 FTM subjects who were given androgen for at least 6 months before hystero-salpingo-oophorectomy was performed. In addition, 100 bilateral mastectomies were performed, allowing a study of the breast tissue. Mean ovarian volume was increased, with histological characteristics of polycystic ovaries (PCO), defined as >12 antral follicles per ovary, observed in 89 patients (79.5%). Endometrial atrophy was observed in 45%. Breast examination revealed marked reduction of glandular tissue and increase of fibrous connective tissue in 93%, without atypical hyperplasia or carcinoma. The present data confirms and expands the putative associations between long-term androgen administration and abnormalities in ovarian architecture with macroscopic and microscopic characteristics of PCO, increased risk of endometrial atrophy and fibrotic breast tissue with marked glandular reduction.

An ex-vivo human intestinal model to study Entamoeba histolytica pathogenesis.

Amoebiasis (a human intestinal infection affecting 50 million people every year) is caused by the protozoan parasite Entamoeba histolytica. To study the molecular mechanisms underlying human colon invasion by E. histolytica, we have set up an ex vivo human colon model to study the early steps in amoebiasis. Using scanning electron microscopy and histological analyses, we have established that E. histolytica caused the removal of the protective mucus coat during the first two hours of incubation, detached the enterocytes, and then penetrated into the lamina propria by following the crypts of Lieberkühn. Significant cell lysis (determined by the release of lactodehydrogenase) and inflammation (marked by the secretion of pro-inflammatory molecules such as interleukin 1 beta, interferon gamma, interleukin 6, interleukin 8 and tumour necrosis factor) were detected after four hours of incubation. Entamoeba dispar (a closely related non-pathogenic amoeba that also colonizes the human colon) was unable to invade colonic mucosa, lyse cells or induce an inflammatory response. We also examined the behaviour of trophozoites in which genes coding for known virulent factors (such as amoebapores, the Gal/GalNAc lectin and the cysteine protease 5 (CP-A5), which have major roles in cell death, adhesion (to target cells or mucus) and mucus degradation, respectively) were silenced, together with the corresponding tissue responses. Our data revealed that the signalling via the heavy chain Hgl2 or via the light chain Lgl1 of the Gal/GalNAc lectin is not essential to penetrate the human colonic mucosa. In addition, our study demonstrates that E. histolytica silenced for CP-A5 does not penetrate the colonic lamina propria and does not induce the host's pro-inflammatory cytokine secretion.

Surgical treatment of rectal cancer: results of a strategy for selective preoperative radiotherapy.

AIM: The indications for preoperative adjuvant therapy in rectal cancer are still a subject of debate. The objective of this study was to analyze the results of surgical resection and selective radiotherapy in a group of high-risk patients (Dukes B and C) taken from a series of 148 consecutive patients with rectal cancer. METHODS: All patients with rectal cancer considered for resection during the period 1994-2004 were prospectively included. The policy was to deliver preoperative radiotherapy in cases of fixed or tethered tumors or when imaging predicted T3 tumors with positive circumferential margins. Other tumors were resected without neoadjuvant therapy. All resections were done using the total mesorectal excision (TME) technique. RESULTS: One hundred and forty-eight consecutive patients underwent rectal resection during the study period. A sphincter-saving technique was carried out in 134 patients (90%). No patient was excluded from the analysis. The perioperative mortality was 2/148 (1.5%). Curative surgery was obtained in 135 patients. The 94 patients with a Dukes B or C tumor formed the high-risk group that was the basis of our study. The mean follow-up in this group was 58 months (range 24-120). Twenty patients (21%) received preoperative radiotherapy (PRT) and 74 (79%) underwent surgical resection alone. A positive circumferential margin, defined as one that was < or =1 mm, was found in seven of the 85 patients (8.2%) for whom this measure was available. The actuarial five-year overall survival was 74%. Local recurrence developed in eight patients (8.4%): four in the PRT group (20%), and four in the non-PRT group (5.4%). Only two patients developed an isolated local recurrence. CONCLUSIONS: Preoperative adjuvant therapy can be safely omitted in patients who demonstrate clear circumferential margins on preoperative imaging, provided that adequate surgery is subsequently performed.