Apoptosis and bcl-2 expression in prostate cancer: significance in clinical outcome after brachytherapy.

PURPOSE: Radiation induced apoptosis of prostate cancer cells may have therapeutic and prognostic significance in patients treated with radiotherapy. We determined whether the ability of prostate tumor cells to undergo apoptosis has potential value for predicting the clinical response of patients with prostate cancer to brachytherapy. MATERIALS AND METHODS: A total of 76 patients with clinical stages T1 to 2 disease who were not receiving adjuvant therapy underwent transperineal implantation with 125iodine or 103palladium seeds and biopsy 7 to 23 months (median 12) after therapy. Nonresponders were classified using the American Society for Therapeutic Radiology and Oncology criteria. The apoptotic index was analyzed using the terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end-labeling assay in archived biopsy specimens from 76 treated and 19 matched pretreatment control patients. Serial sections of prostatic tumors were also evaluated for the expression of bax and bcl-2 proteins (apoptosis regulators) by immunohistochemical testing. RESULTS: A significant increase in the apoptotic index was detected in post-brachytherapy compared with pretreatment prostate specimens (3.1% versus 2%, p <0.05), as well as in patients with negative biopsy at followup compared with those with persistent malignancy (3.4% versus 1.8%, p = 0.02). In addition, there was a significant elevation in bcl-2 expression in prostatic tissue in patients with treatment failure compared with responders (30.5% versus 13.1%, p <0.05). CONCLUSIONS: To our knowledge this is the first study to establish a correlation of apoptosis induction and bcl-2 over expression with treatment outcome in patients with prostate cancer after brachytherapy. Our findings have significant clinical implications for identifying the value of the apoptotic index and bcl-2 expression in prostatic tumors for predicting the therapeutic response to brachytherapy.

Use of in situ spermatic cord patch for inguinal lymph node dissection.

Inguinal lymph node dissection for diagnosis of metastatic squamous cell carcinoma of the penis can cause significant morbidity and mortality for patients due to local wound breakdown, lymphedema, and vascular erosion. Various methods have been described to cover exposed femoral vessels to preserve their integrity, the most common being transposition of the sartorius muscle. We describe the successful use of in situ spermatic cord for coverage of the femoral artery and vein after inguinal lymph node dissection for squamous cell carcinoma of the penis in two patients. To our knowledge, this has not been previously described and is a simple and successful alternative way to cover the femoral vessels after inguinal lymphadenectomy.

Radiation-induced apoptosis: predictive and therapeutic significance in radiotherapy of prostate cancer (review).

Current therapy for advanced prostate cancer is hampered by the propensity of the disease to progress from an androgen-dependent state to an androgen-independent state. Current treatment for advanced disease is palliative. Therefore, the therapeutic goal for prostate cancer treatment today is to arrest the disease at an early state when it is still localized to the gland. The standard treatment for clinically localized disease is radical prostatectomy or radiation therapy by way of external beam irradiation or local radioactive seed implants (brachytherapy). In advanced disease, the use of radiation therapy is limited to palliation of pain secondary to bone metastases and for spinal cord compression. Tracking residual disease and predicting outcome is limited to following the level of prostate specific antigen (PSA) production, evaluating for bone or solid organ metastasis, and analyzing their preoperative clinical stage, PSA and Gleason's score. Apoptosis as a molecular process of genetically regulated cell death has a critical endpoint that coincides with the goal of successful treatment of human malignancies. Since in cancer treatment the therapeutic goal is to trigger tumor-selective cell death, activation of the apoptotic pathway in prostatic tumor cells offers attractive and potentially effective therapeutic targets. As our understanding of the vital role of apoptosis in the development and growth of the prostate gland has expanded, numerous genes that encode apoptotic regulators have been identified that are severely impaired in prostate tumors. Human prostate cancer cells undergo apoptosis in response to androgen ablation, chemotherapeutic agents and ionizing irradiation. The expression of apoptotic modulators within individual prostate tumors appears to correlate with the cancer cell's sensitivity to traditional therapeutic modalities, including radiotherapy. No strict correlation between radiation-induced apoptosis and longevity of prostate cancer patients has emerged, possibly because the ability to achieve an initial remission alone does not adequately predict long-term outcome and patient survival. In this review we summarize the current understanding of the effects of radiation therapy on prostatic tumor cells within the context of the therapeutic significance of radiation-induced apoptosis in the effective elimination of androgen independent prostate cancer cells. As we enter a new millenium, identification of distinct molecular markers predictive of therapeutic response of prostatic tumors to radiation therapy may afford alternative prognostic indicators in optimizing our treatment protocols for advanced disease.

The plug and patch: a new technique for repair of corporal perforation during placement of penile prostheses.

PURPOSE: Proximal corporal perforation is an uncommon intraoperative complication during placement of a penile prosthetic device. Unrecognized corporal perforation can result in migration or malfunction of the prosthesis. A windsock repair using a nonabsorbable mesh plug has been described. We describe a new technique called the plug and patch to treat this complication. MATERIALS AND METHODS: From July 1994 to May 1999, 175 patients underwent placement of a penile prosthesis at our institution. Of the patients 8 (4.5%) had proximal corporal perforation. Each perforation was repaired using our plug and patch technique. A 5x7 cm. polyglycolic acid patch was folded on itself and passed into the area of the corporal perforation to act as a plug. A solitary absorbable suture was placed affixing the tail of the patch to the corpora. The corpus was subsequently re-dilated and remeasured, and the prosthesis was placed as usual. RESULTS: All 8 patients were satisfied with the penile prosthesis. There were no infectious complications or proximal migration of the prosthetic cylinders. The plug repair added an average of 6 minutes to the operating time. Only 1 patient had discomfort in the area of the repair, which resolved spontaneously approximately 6 weeks postoperatingly. CONCLUSIONS: The plug and patch is a rapid and effective technique to repair intraoperating proximal corporal perforations. Potential advantages include shorter operating time, technical simplicity and the use of only absorbable materials. This technique may result in lower infection rates compared to the standard windsock repair.