PurposeWe conducted an open-label, single-arm Phase I/II clinical trial in metastatic CRPC (mCRPC) patients eligible for docetaxel combined with treatment with autologous mature dendritic cells (DCs) pulsed with killed LNCaP prostate cancer cells (DCVAC/PCa). The primary and secondary endpoints were safety and immune responses, respectively. Overall survival (OS), followed as a part of the safety evaluation, was compared to the predicted OS according to the Halabi and MSKCC nomograms.Experimental designTwenty-five patients with progressive mCRPC were enrolled. Treatment comprised of initial 7 days administration of metronomic cyclophosphamide 50 mg p.o. DCVAC/PCa treatment consisted of a median twelve doses of 1 × 107 dendritic cells per dose injected s.c. (Aldara creme was applied at the site of injection) during a one-year period. The initial 2 doses of DCVAC/PCa were administered at a 2-week interval, followed by the administration of docetaxel (75 mg/m2) and prednisone (5 mg twice daily) given every 3 weeks until toxicity or intolerance was observed. The DCVAC/PCa was then injected every 6 weeks up to the maximum number of doses manufactured from one leukapheresis.ResultsNo serious DCVAC/PCa-related adverse events have been reported. The median OS was 19 months, whereas the predicted median OS was 11.8 months with the Halabi nomogram and 13 months with the MSKCC nomogram. Kaplan-Meier analyses showed that patients had a lower risk of death compared with both MSKCC (Hazard Ratio 0.26, 95% CI: 0.13–0.51) and Halabi (Hazard Ratio 0.33, 95% CI: 0.17–0.63) predictions. We observed a significant decrease in Tregs in the peripheral blood. The long-term administration of DCVAC/PCa led to the induction and maintenance of PSA specific T cells. We did not identify any immunological parameter that significantly correlated with better OS.ConclusionsIn patients with mCRPC, the combined chemoimmunotherapy with DCVAC/PCa and docetaxel was safe and resulted in longer than expected survival. Concomitant chemotherapy did not preclude the induction of specific anti-tumor cytotoxic T cells.
Introduction
Greater acceptance of sexual minorities has enabled people with transsexualism access to adequate treatment and social integration. Gender reassignment surgery is a complex phase in the care of transsexual patients. In response to a greater volume of patients, surgical techniques have evolved and the outcome in patients with male-to-female transsexualism is now a very accurate imitation of female genitalia, enabling sexual intercourse with orgasm.
Aim
To evaluate the results of surgical reassignment of genitalia in male-to-female transsexuals.
Methods
A retrospective 3-month follow-up study of patients’ opinions following gender reassignment surgery in 129 patients having a primary procedure (eight of whom had later sigmoideocolpoplasty) and five patients undergoing reoperation following an initial unsuccessful procedure at other units. All patients were male transsexuals. The surgical techniques are described in detail.
Main Outcome Measures
Sexual functions and complications 3 months after surgery.
Results
All patients were satisfied with the first phase operation. Thirteen patients (9.7%) underwent successful sigmoideocolpoplasty. Main complications were as follows: rectal lesions developing during preparation of the vaginal canal (1.5%); bleeding from the stump of the shortened urethra in the first 48 hours postoperatively requiring secondary suturing (4.5%); temporary urinary retention requiring repeated insertion of urinary catheters for up to 6 days (5.2%); and healing of the suture between the perineum and the posterior aspect of the vaginal introitus healing by secondary intention (5.2%). The neoclitoris had erogenous sensitivity in 93.9% of patients and 65.3% reached orgasm in the first 3 months.
Conclusions
Surgical conversion of the genitalia is a safe and important phase of the treatment of male-to-female transsexuals.
Objective To describe the techniques and outcome of genital and urethral reconstructive surgery during gender conversion as part of the treatment of transsexuals. Patients and methods From 1992 to 1999, 82 patients were surgically converted after previous sexual and hormonal therapy. Using the male genital tissue to create new female genitalia, and vice versa, 30 male and 52 female transsexuals were converted. For maleto-female transsexuals, the technique of penile skin inversion was used 29 times and sigmoidocolpoplasty ®ve times (in one patient primarily and in four patients to correct inadequate neovaginal size after penile skin inversion). In female-to-male transsexuals, 28 metaidoioplasties and seven neophalloplasties were performed using the groin skin-¯ap technique, with 42 breast reductions also included as a part of the therapy. Results Surgical gender reassignment of the male transsexuals resulted in replicas of female genitalia which enabled coitus with orgasm. Depending on the technique used in the reverse conversion, the patient maintained the ability to attain orgasm, and in many cases had a satisfactory appearance of the neopenis, with the potential to void while standing. Conclusions The morphological proportions of each patient vary, and the different shapes and sizes of the tissues can be used for plastic operations. Thus the modelling of each individual genital in transsexuals can be considered`original'.
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