In Utero and Lactational TCDD Exposure Increases Susceptibility to Lower Urinary Tract Dysfunction in Adulthood.

Benign prostatic hyperplasia, prostate cancer, and changes in the ratio of circulating testosterone and estradiol often occur concurrently in aging men and can lead to lower urinary tract (LUT) dysfunction. To explore the possibility of a fetal basis for the development of LUT dysfunction in adulthood, Tg(CMV-cre);Nkx3-1(+/-);Pten(fl/+) mice, which are genetically predisposed to prostate neoplasia, were exposedin uteroand during lactation to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD, 1 µg/kg po) or corn oil vehicle (5 ml/kg) after a single maternal dose on 13 days post coitus, and subsequently were aged without further manipulation, or at 8 weeks of age were exposed to exogenous 17 ß-estradiol (2.5 mg) and testosterone (25 mg) (T+E2) via slow release subcutaneous implants.In uteroand lactational (IUL) TCDD exposure in the absence of exogenous hormone treatment reduced voiding pressure in adult mice, but otherwise had little effect on mouse LUT anatomy or function. By comparison, IUL TCDD exposure followed by exogenous hormone treatment increased relative kidney, bladder, dorsolateral prostate, and seminal vesicle weights, hydronephrosis incidence, and prostate epithelial cell proliferation, thickened prostate periductal smooth muscle, and altered prostate and bladder collagen fiber distribution. We propose a 2-hit model whereby IUL TCDD exposure sensitizes mice to exogenous-hormone-induced urinary tract dysfunction later in life.

Gliosarcoma: A rare primary CNS tumor. Presentation of two cases.

INTRODUCTION: Gliosarcoma is a very rare primary mixed tumor in the central nervous system, with a biphasic pattern consisting of glial and malignant mesenchymal elements. Its onset is between the fourth and sixth decade of life, and it has a male/female ratio of 1.8/1. Here we present two cases of Gliosarcoma treated in our department. DISCUSSION: The monoclonal or biclonal origin of its biphasic nature is still subject to debate; hence the importance of its diagnosis and histogenesis. RESULTS: Standard treatment consists in surgical resection of the tumor followed in some cases by external radiotherapy and chemotherapy.

Molecular evidence of a new strain of Ehrlichia canis from South America.

Blood samples from dogs with clinical signs compatible with ehrlichiosis were examined for infection of Ehrlichia canis using PCR, multiplex real-time PCR, and DNA sequencing analysis. Eleven of 25 samples were positive for a new strain of E. canis. This is the first molecular identification of E. canis infection in dogs from Peru.

Tegafur and 5-fluorouracil pelvic tissue concentrations in rectal cancer patients receiving preoperative chemoradiation

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Background and purpose. To investigate the presenceof 5-Fluorouracil (5-FU) in pelvic tissue afteroral administration of tegafur. To measure tegafurand 5-FU concentrations in normal rectal mucosa,perirectal fat and residual tumor in rectal cancerpatients receiving preoperative chemoradiation. Tocorrelate drug concentrations with cancer downstagingeffects.Patients and methods. Three tissue samples takenfrom 16 surgical specimens after recto-sigmoid resectionwere analyzed. Tegafur and 5-FU concentrationswere measured using high-performance liquidchromatography. 16 patients with locallyadvanced rectal cancer were treated with preoperativepelvic irradiation (45-50 Gy) sensitized withoral tegafur (400 mg for every 8 hours daily). Sevenpatients received a precharge dose of tegafur (400mg oral every 8 hours) 24 hours before surgery.Results. In 8 of the 9 patients who did not receive aprecharge dose, detectable levels of tegafur wereobserved in fat tissue, normal mucosa and tumor,but detectable 5-FU levels were only observed inone patient. Mean concentrations (ranges) for tegafurin fat, normal mucosa and tumor in patientswithout the precharge dose were 72.19 (12.1-205.6),179.53 (11.30-727.7) and 252.35 (27.9-874.6) ng/g, respectively;mean concentrations for 5-FU in thesame samples were 0.95, 1.92 and 2.68 ng/g (1 patient),respectively.In patients receiving a tegafur precharge, both tegafurand 5-FU were present in all tissue sampleswith the exception of 2 fat samples, in which drugconcentrations were undetectable.5-FU levels were higher in tumor than other sites,with a median value of 68.24 ng/g (range 3.8-283.05ng/g). Tegafur levels were also higher in tumorsamples than other sites (mean 3446.53 ng/g, range1044.5-7847.0 ng/g), except in 2 patients who hadhigher levels of tegafur in normal mucosa.Conclusions. Tegafur and 5-FU are not always presentin pelvic tissues 5 to 6 weeks after oral administrationof tegafur. Both drugs were present in thetissues analyzed, in relevant concentrations, 24hours after oral administration of tegafur. The dataobtained suggest a tendency (not significant) towarda correlation between levels of 5-FU presentin the residual tumor and cancer downstaging

Intraoperative presacral electron boost following preoperative chemoradiation in T3-4Nx rectal cancer: initial local effects and clinical outcome analysis.

BACKGROUND AND PURPOSE: To analyze early results of a single institution experience using adjuvant intraoperative electron radiation therapy (IOERT) presacral boost in locally advanced rectal cancer following preoperative chemoradiation. MATERIALS AND METHODS: In a 63 month period (March 1995-June 2000), 100 consecutive T(3-4)N(x) rectal cancer patients were treated with preoperative chemoradiation (45-50 Gy plus oral Tegafur or 5-Fluorouracil continuous intravenous infusion), radical surgery and IOERT presacral boost (mean dose, 12.5 Gy; range, 10-15 Gy). Adjuvant chemotherapy (5-FU-leucovorin: 4-6 cycles) was given to 52 patients. The median age was 63 years, and 39 patients were >or=70 years old (65 males). Clinical staging was performed with computed tomography (94%) and/or endorectal ultrasound (71%) categorizing 90 cT(3), 10 cT(4), 20 cN(x), and 36 cN(+). Abdomino-perineal resection was performed in 41 cases. RESULTS: The IOERT cancellation rate was 6%. With a median follow-up of 23 months in IOERT treated patients, three developed pelvic recurrence: one anastomotic and one in the posterior vaginal wall (simultaneously with distant metastatic disease); and one presacral (in-field IOERT) as the only site of initial failure. Distant metastasis has been observed in 14 patients (exceptionally in pT(0-1) downstaged patients: 1/20; 5%). Overall treatment tolerances, including neoadjuvant and surgical segments, were acceptable. The actuarial 4-year estimations of local control, disease-free and overall survival are 94, 75 and 65%, respectively. CONCLUSIONS: IOERT electron boost to the presacral region is feasible to integrate systematically in the intensive combined treatment of locally advanced rectal cancer, including neoadjuvant chemoradiation segment. Topography of pelvic recurrences identified 2/3 relapses located in non-IOERT boosted anatomic intrapelvic sites: posterior vaginal wall and anastomotic suture. Presacral recurrence in locally advanced rectal cancer seems to be of low incidence, in a non-subspecialized academic surgical practice coordinated with a multidisciplinary oncology evaluation context, if an IOERT boost is included as a component of treatment together with preoperative chemoradiation.