ID2-VEGF-related Pathways in the Pathogenesis of Kaposi's Sarcoma: A Link Disrupted by Rapamycin

The Id-proteins are a family of four related proteins implicated in the control of differentiation and cell-cycle progression. Down-regulation of Id-gene expression is essential for the differentiation of several cell types. In addition, deregulated Id2 activity inhibits the Rb tumor suppressor pathway and promotes the expression of vascular endothelial growth factor (VEGF). Several members of VEGF family could be involved in Kaposi's sarcoma (KS) development and progression. Lymphatic vascular endothelial hyaluronan receptor-1 (LYVE-1) is the first marker of lymphatic endothelial competence during development in the mature vasculature, and is also expressed on KS spindle cells. Rapamycin (RAPA), an immunosuppressive drug, has been shown to reverse KS growth and to reduce tumor angiogenesis. We evaluate, in transplantation-associated KS and in cultured KS-cells the RAPA effect on Id2 and on de novo lymphangiogenesis. Markers of lymphatic-endothelial-cells (VEGFR-3, LYVE-1) and Id2, expressed at low levels within the normal skin, were up-regulated in KS and returned to normal levels after RAPA introduction. The association between Id2 and lymphangiogenesis is suggested by co-localization of Id2, VEGFR-3 and LYVE-1. RAPA inhibition on Id2 expression was confirmed in vitro in KS-cells, both in basal conditions and upon stimulation with VEGF. In conclusion, our data would suggest a novel molecular mechanism for the antineoplastic effects of RAPA in posttransplant KS.     

Urethral Corpus Spongiosum Amyloidosis Presenting with Urethrorrhagia During Erection

IntroductionUrethral amyloidosis is a rare, probably inflammatory condition usually presenting with hematuria and obstructive urinary symptoms, thus mimicking urethral malignancy. After histological confirmation of the diagnosis, treatment can be expectant or symptomatic.AimTo report an unusual cause of urethrorrhagia occurring only during erection in an otherwise healthy man.MethodsA 30-year-old man presented with a 5-month history of urethrorrhagia occurring only during erection, and with a painless palpable nodule in his penile urethra clearly visible on urethral US and magnetic resonance imaging, but not on urethroscopy.ResultsThe patient underwent wide surgical excision of the urethral nodule and grafting of the urethral defect with a pedicled preputial flap. Histological examination revealed isolated amyloid of urethral corpus spongiosum.ConclusionsIsolated urethrorrhagia during erection and without urinary symptoms can be the presenting sign of urethral amyloidosis involving corpus spongiosum rather than the urethral lumen; in such cases, surgical exploration, wide urethral excision and grafting are mandatory. Cormio L, Sanguedolce F, Pentimone S, Perrone A, Annese P, Turri FP, Bufo P, and Carrieri G. Urethral corpus spongiosum amyloidosis presenting with urethrorrhagia during erection. J Sex Med 2009;6:2915–2917.     

Angiogenesis extent and expression of matrix metalloproteinase-2 and -9 agree with progression of ovarian endometriomas

BACKGROUND: Changes in angiogenesis and expression of extracellular matrix-degrading enzymes have been substantiated in tumour changeover and progression. METHODS: Tissues from 44 biopsies of stage III and IV ovarian endometriomas, and 10 biopsies of normal (control) endometrium were investigated immunohistochemically to count microvessels, and by in situ hybridization to assess the expression of mRNA of matrix metalloproteinase-2 (MMP-2) and MMP-9. Implants of the tissues were investigated in the chick embryo chorioallantoic membrane (CAM) assay to determine their angiogenic capacity. RESULTS: The endometriomas displayed significantly higher counts than normal endometria and the highest values were associated with the deepest invasion level (stage IV). Microvessels localized in close association with ectopic endometrial cells in the form of winding and arborized tubes, often dilated in microaneurysmatic segments. These were absent in normal endometrium. Expression of MMP-2 and MMP-9 mRNA, evaluated as percentages of positive biopsies and intensity of expression, was up-regulated in endometriomas and more pronounced in stage IV. MMP-2 and MMP-9 mRNA were also expressed by host stromal cells, including microvascular endothelial cells, fibroblasts and macrophages, whereas the control endometrium showed very little expression of MMP-2 mRNA in a few endothelial cells and no expression of MMP-9 mRNA. Implants from stage IV endometrioma induced a more intense vasoproliferative response than those from stage III, while no vasoproliferative response was induced by the normal endometrium. CONCLUSION: These data suggest that angiogenesis and degradation of extracellular matrix occur together in endometriosis and are more pronounced in stage IV, and that endometriosis cells and some host stromal cell populations co-operate in disease progression.     

Nephrostomy in percutaneous nephrolithotomy (PCNL): does nephrostomy tube size matter? Results from The Global PCNL Study from The Clinical Research Office Endourology Society

Purpose

To explore the relationships between nephrostomy tube (NT) size and outcome of percutaneous nephrolithotomy (PCNL).

Methods

The Clinical Research Office of the Endourological Society (CROES) prospectively collected data from consecutive patients treated with PCNL over a 1-year period at 96 participating centers worldwide. This report focuses on the 3,968 patients who received a NT of known size. Preoperative, surgical procedure and outcome data were analyzed according to NT size, dividing patients into two groups, namely small-bore (SB; nephrostomy size ≤ 18 Fr) and large-bore (LB; nephrostomy size > 18 Fr) NT.

Results

Patients who received a LB NT had a significantly lower rate of hemoglobin reduction (3.0 vs. 4.3 g/dL; P < 0.001), overall complications (15.8 vs. 21.4 %; P < 0.001) and a trend toward a lower rate of fever (9.1 vs. 10.7 %). Patients receiving a LB NT conversely had a statistically, though not clinically significant, longer postoperative hospital stay (4.4 vs. 4.2 days; P = 0.027). There were no differences in urinary leakage (0.9 vs. 1.3 %, P = 0.215) or stone-free rates (79.5 vs. 78.1 %, P = 0.281) between the two groups.

Conclusions

LB NTs seem to reduce bleeding and overall complication rate. These findings would suggest that if a NT has to be placed, it should better be a LB one.     

Clinical features of hepatic metastasis in patients with ovarian cancer

The purpose of this study was to investigate the clinical features of hepatic metastasis in patients with epithelial ovarian cancer. From 1998 to 2002, all women with hepatic metastasis from ovarian cancer were identified at the University of Bari. Twenty-nine patients identified included one having stage IIC, one stage IIIA, two stage IIIB, 17 stage IIIC, and eight stage IVB. Eight women had hepatic metastasis at the time of the diagnosis of ovarian cancer (group I), 10 patients had hepatic metastasis as first recurrence (group II), and 11 (group III) as a second relapse. The median survival from the time of liver metastasis diagnosis was 19 months in group I patients, 24 months in group II patients, and 10 months in group III patients. No statistical differences in survival were seen among the three groups (P = 0.7). Cell type, performance status at the time of the primary tumor diagnosis, number of hepatic lesions, the presence of other sites of disease at the time of hepatic metastasis, and platinum-based chemotherapy were significantly related to survival. Better performance status, serous cell-type tumor, single hepatic lesion, the absence of other sites of disease, and platinum-based chemotherapy are good prognostic factors.     

Hormone replacement therapy on ovarian and uterine cancer risk and cancer survivors: how shall we do no harm?

This article will focus on the results of the Women's Health Initiative on the effects of hormone replacement therapy on coronary heart disease, stroke, venous thromboembolism, breast cancer, and colorectal cancer. Data from other relevant trials, including the most recent data on ovarian and uterine cancer risk and on gynecologic cancer patients, are also discussed to provide some guidelines on prescribing hormone replacement therapy in clinical practice, particularly in gynecologic cancer survivors.     

Polymyositis and vaginal carcinoma

Summary The strange association of Dermatomyositis-Polymyositis (DM-PM) and cancer has been known for many years. We present the case of a 57-year-old woman with polymyositis refractory to steroid therapy, in whom extensive investigation finally revealed a squamous cell carcinoma of the vagina. The clinical course of myositis paralleled the course of vaginal cancer, with complete resolution of symptoms after radiotherapy for the malignancy.