pT2 classification for renal cell carcinoma. Can its accuracy be improved?

PURPOSE: The 2002 tumor classification for renal cell carcinoma (RCC) classifies pT2 tumors as more than 7 cm in greatest dimension, limited to the kidney. In this study we determined whether a size cutoff point exists within pT2 tumors and whether such subclassification would further improve the accuracy of the current tumor classification. MATERIALS AND METHODS: We studied 544 patients with unilateral, sporadic pT2 RCC treated with radical nephrectomy or nephron sparing surgery between 1970 and 2000. The association of tumor size with death from RCC was examined using martingale residuals from a Cox proportional hazards regression model to determine the optimal size cutoff point. RESULTS: There were 204 deaths from RCC a median of 3.8 years following nephrectomy. Univariately tumor size was significantly associated with death from RCC (risk ratio 1.08, 95% CI 1.04 to 1.13, p <0.001). A scatterplot of tumor size vs expected risk of death per patient suggested that a cutoff point between 9 and 10 cm was appropriate. When adjusted for regional lymph node involvement and distant metastases, the 10 cm cutoff point performed better than the 9 cm point (risk ratio 1.42, 95% CI 1.07 to 1.90, p = 0.017 vs 1.22, 95% 0.86 to 1.72, p = 0.268). Therefore, we propose using a 10 cm cutoff point to subclassify patients into pT2a and pT2b. CONCLUSIONS: Our data suggest that the prognostic accuracy of the 2002 pT2 tumor classification can be further improved by subclassifying patients with tumors greater than 7 and less than 10 cm into a pT2a category, and those with tumors 10 cm or greater into a pT2b category.     

DOES SILDENAFIL COMBINED WITH TESTOSTERONE GEL IMPROVE ERECTILE DYSFUNCTION IN HYPOGONADAL MEN IN WHOM TESTOSTERONE SUPPLEMENT THERAPY ALONE FAILED?

PURPOSE: We evaluated the efficacy of testosterone gel (T-gel) alone and in combination with sildenafil in hypogonadal patients with erectile dysfunction (ED). MATERIALS AND METHODS: A total of 49 hypogonadal men (mean age 60.7 years) with ED participated for a mean of 20.2 months. Blood was tested for total and bioavailable testosterone, and prostate specific antigen. Sexual function was assessed using the International Index of Erectile Function questionnaire and a global assessment question (GAQ). Men received 1% 5 gm T-gel for 6 months, and 100 mg sildenafil was added to those with a "no" response to the GAQ after 3 months on testosterone supplement. RESULTS: A total of 31 patients reported significant improvement in the sexual desire domain (from a mean +/- SD of 4.2 +/- 0.8 to 8.6 +/- 0.4) and erectile function (EF) domain (from 13.6 +/- 1.9 to 27 +/- 0.8) following treatment with testosterone supplement alone. One patient was excluded from study after urinary retention developed and 9 reported irritation at the gel application site. In spite of normalization of total and bioavailable testosterone values, and significant improvement of sexual desire domain scores, the EF of 17 men remained less than 26 or they responded "no" to the GAQ. These men received combined T-gel and sildenafil, after which all graded EF greater than 26 and responded positively to the GAQ. CONCLUSIONS: Combined treatment with sildenafil and T-gel has a beneficial effect on ED in hypogonadal patients in whom treatment with testosterone supplement alone failed.     

经内镜扩张治疗食管狭窄

摘要目的用内镜食管扩张治疗食管狭窄,介绍纤光内镜下扩张器的使用方法。方法用 Savary-Gilliard 探条和Key Med 扩张器,对食管狭窄病人进行内镜扩张。结果 45例食管狭窄病人,作了157次内镜扩张治疗。症状Ⅰ级改善13.3/(6/45),Ⅱ级改善4.4%(2/45),治愈率80%(36/45),总有效率97.8%(44/45),1例食管扩张不成功。全组未发生任何严重并发症和因食管扩张术而死亡者。结论认为这两种扩张器治疗食管狭窄,方法简便、安全、疗效确实,值得推广使用。     

Long-term results of the bulbourethral sling procedure

PURPOSE: We evaluated the long-term efficacy of the male bulbourethral sling procedure in the treatment of post-radical prostatectomy urinary incontinence. MATERIALS AND METHODS: Between October 1994 and June 2000, 95 patients with post-radical prostatectomy incontinence underwent bulbourethral sling placement with tetrafluoroethylene bolsters at our hospital. Ultimately 71 of these patients responded to our questionnaire and they were classified into 2 groups. Group 1 consisted of 62 patients who had not undergone prior radiation therapy and group 2 consisted of 9 who had undergone radiation therapy before the sling procedure. Patients were asked to respond to questions regarding continence status as well as the validated Incontinence Quality of Life and International Prostate Symptom Score questionnaires. RESULTS: Mean followup from the most recent sling procedure was 4 years (range 0.27 to 6.55). Average patient age at questionnaire response was 74 years. A total of 86 procedures were performed on 71 patients. Of the 71 patients 7 underwent either sling removal or artificial urinary sphincter placement and were excluded from questionnaire analysis. Including retightening procedures 68% of the patients (72% of group 1, 43% of group 2) required 2 or less pads daily. Of the patients 36% (42% of group 1 and 14% of group 2) required 0 pads. CONCLUSIONS: The male bulbourethral sling procedure remains an effective treatment for post-prostatectomy incontinence at 4-year followup.     

Laparoscopic radical prostatectomy

PURPOSE: After the pioneering period when only few teams were performing the procedure, the laparoscopic approach to radical prostatectomy has become widespread with several technical variations. A comprehensive review of the published literature on laparoscopic radical prostatectomy was performed to determine the current state of the art of this surgical innovation in terms of perioperative parameters, functional results and cancer control. MATERIALS AND METHODS: English language, peer reviewed articles published before June 2004 concerning laparoscopic radical prostatectomy were found by MEDLINE query. All articles were analyzed and none were a priori excluded. Conclusions were drawn from series of 50 or more patients. RESULTS: Laparoscopic radical prostatectomy is being performed at multiple centers worldwide using various surgical approaches and technologies. Analysis of perioperative parameters, including surgical blood loss, operative time, complications and convalescence, demonstrated low morbidity and showed a clear trend toward improvement with increased experience. The reported positive surgical margin rates were lower in more recent series. As measured by prostate specific antigen recurrence and disease-free intervals, oncological results and cancer control rates are difficult to ascertain in the immature series published to date. Functional results in terms of postoperative urinary and sexual function appear encouraging. CONCLUSIONS: Overall the current operative, oncological and functional results of laparoscopic radical prostatectomy appear to approximate those of open radical retropubic prostatectomy. These results justify the considerable interest of the urological community in laparoscopy, as evidenced by its widespread application. Nevertheless, longer followup and more mature data are needed definitively to establish laparoscopic radical prostatectomy as an alternative to the retropubic approach.     

Update on chemotherapy for advanced bladder cancer

PURPOSE: Recent years have seen several advances in the treatment of locally advanced and metastatic bladder cancer. We summarize the current state of the art for advanced bladder cancer treatment. MATERIALS AND METHODS: A comprehensive review of published, prospective phase II/III clinical trials and retrospective analyses of patients with advanced bladder cancer was performed. RESULTS: Adjuvant and neoadjuvant chemotherapeutic strategies around the time of radical cystectomy have been used to decrease the risk of subsequent metastatic disease. Although the benefit of adjuvant chemotherapy remains unproven, neoadjuvant chemotherapy is associated with a modest 5% to 6% absolute survival benefit in 2 meta-analyses of the available data. Chemoradiation is feasible and effective in some patients, allowing bladder preservation with an acceptable risk of progression. Randomized, phase III data comparing methotrexate, vinblastine, doxorubicin and cisplatin chemotherapy to gemcitabine/cisplatin showed similar response proportions and overall survival with less toxicity in the gemcitabine/cisplatin arm. This has led to the widespread use of gemcitabine/cisplatin as first line chemotherapy for metastatic bladder cancer. The optimal agents and regimens for second line chemotherapy remain undefined. Similarly biological and targeted therapies for advanced bladder cancer remain investigational. CONCLUSIONS: Combination cisplatin based neoadjuvant chemotherapy may benefit patients with locally advanced bladder cancer. Gemcitabine/cisplatin has replaced methotrexate, vinblastine, doxorubicin and cisplatin as the regimen of choice in patients with good renal function. The optimal regimens for the medically unfit patient and second line chemotherapy remain undefined. The development of targeted therapies, less toxic regimens and improved cytotoxic agents are necessary to improve outcomes.     

Use of the novel marker BLCA-1 for the detection of bladder cancer

PURPOSE: Bladder cancer specific nuclear structural alterations have been identified. We examined the expression pattern of one of these proteins, BLCA-1, in tissue and urine samples from individuals with bladder cancer as well as in samples from normal controls. MATERIALS AND METHODS: BLCA-1 sequence data were used to produce antibodies to this protein, which were used in immunoblot and enzyme-linked immunosorbent assays. RESULTS: BLCA-1 was detectable in tissue from patients with bladder cancer but not in normal adjacent areas of the bladder or in normal donor bladder tissue. This protein was also detectable in the urine of patients with bladder cancer by immunoblot and immunoassay. Using a cutoff of 0.025 optical density units (absorbance value) BLCA-1 was detected in 20 of 25 urine samples from patients with bladder cancer but in only 6 of 46 normal, high risk, prostate or renal cancer samples tested, resulting in a test with 80% sensitivity and 87% specificity. Expression of this protein did not appear to correlate with tumor grade. CONCLUSIONS: This research indicates that BLCA-1 is a urine based marker of bladder cancer which may be useful for the detection of this disease.     

Neoadjuvant methotrexate, vinblastine, doxorubicin and cisplatin for histologically proven lymph node positive bladder cancer

PURPOSE: We gained insight into the effect of neoadjuvant chemotherapy and subsequent surgery in patients with bladder cancer with tumor positive lymph nodes. MATERIALS AND METHODS: A total of 52 patients with histologically proven positive lymph nodes (by lymph node dissection or aspiration cytology) were treated with chemotherapy and post-chemotherapy surgery in case of partial or complete response. We evaluated response in the primary tumor and lymph nodes, long-term clinical outcome, and clinicopathological features potentially predictive of survival. RESULTS: Complete response, partial response and stable/progressive disease were attained in 29%, 57% and 14%, and resulted in a 5-year survival of 42%, 19% and 0%, respectively. Objective response (HR 4.1), especially complete response (HR 8.0), was independently associated with survival. The prognostic values of lymph node status and bladder tumor status after methotrexate, vinblastine, doxorubicin and cisplatin were evaluated separately. A tumor negative bladder combined with tumor negative nodes were associated with improved survival (HR 4.4) as was a tumor negative lymph node region in the presence of residual bladder disease (HR 2.8). All patients with post-chemotherapy tumor positive nodes died within 2 years. In resected specimens residual disease was found in 4 of 15 clinically complete responders while no tumor could be detected in 3 of 29 clinically assessed as partial responders. CONCLUSIONS: Response to chemotherapy is associated with improved survival, and our data suggest that lymph node status after methotrexate, vinblastine, doxorubicin and cisplatin is more important than local tumor status in this aspect. In the absence of reliable noninvasive methods, post-chemotherapy surgery in this series was the most adequate method of response evaluation and in limited partial responders led to long-term progression-free survival.     

Radical cystectomy for primary neuroendocrine tumors of the bladder: the university of southern california experience

PURPOSE: Primary neuroendocrine tumors of the bladder are rare and they include small and large cell variants. We reviewed our experience with treating these tumors with radical cystectomy to evaluate their histopathological characteristics and clinical outcomes. MATERIALS AND METHODS: From August 1971 to June 2004, 2,005 patients underwent radical cystectomy for primary bladder cancer at our institution, of whom 25 (1.2%) had neuroendocrine tumors of the bladder, including small cell carcinoma in 20 and large cell carcinoma in 5. Pure neuroendocrine-type histology was identified in 16 cases, including 1 with small and large cell features, while the remaining 9 had mixed histology, that is transitional cell carcinoma in 8 and adenocarcinoma in 1. Multi-agent chemotherapy was administered to 14 patients. RESULTS: Median patient age was 68 years (range 40 to 82) and 19 patients were male (76%). A total of 19 patients (76%) had lymph node involvement, of whom 2 had small liver metastases found intraoperatively, while only 4 (16%) had organ confined tumors and 2 (8%) had extravesical, node negative disease. These tumors tended to have a flat, ulcerative gross appearance with lymphovascular invasion, carcinoma in situ and necrosis present microscopically. Median followup was 11.8 years (range 18 days to 15.1 years). Five-year overall and recurrence-free survival was 10% and 13%, respectively. There was no significant survival difference between small and large cell carcinoma. Mixed histologies tended to do better than pure neuroendocrine tumors, although this did not attain statistical significance (p = 0.064). Patients receiving multimodality therapy had significantly better overall (p = 0.051) and recurrence-free (p = 0.003) survival than those treated with cystectomy alone. CONCLUSIONS: Neuroendocrine tumors of the bladder usually present with advanced pathological stage and portend a poor prognosis. Adjuvant chemotherapy protocols may provide improved survival compared with cystectomy alone.     

Local recurrence after cystectomy and survival of patients with bladder cancer: a population based study in greater amsterdam

PURPOSE: We determined retrospectively in a population based study the survival of patients with bladder cancer and the local recurrence rate (LRR) after cystectomy. MATERIALS AND METHODS: All patients with bladder cancer diagnosed between 1988 and 2001 (vital status updated until September 2003) were selected from the Amsterdam Cancer Registry, which covers a population of 2.84 million individuals. For all patients who underwent cystectomy between 1988 and 1997 at 18 participating hospitals information on local recurrence and vital status was collected from the medical records. RESULTS: Five-year relative survival in all 8,321 bladder cancer cases combined was 75%. For clinical stage 0-a this was 99%, decreasing to 85% for stage 0-is and 82% for stage I, and to 44%, 28% and 9% for stages II to IV, respectively. Five-year relative survival after cystectomy was 81%, 44% and 23% for stages II to IV, respectively. The LRR after cystectomy was 19% in all 566 cases and all institutions combined. The LRR increased with higher pT stage and it achieved 11%, 23% and 31% for stages II to IV, respectively. It was slightly lower at oncological centers than at community hospitals (18% vs 20%, not significant). CONCLUSIONS: Survival is higher than the European average but below the value in the United States. Only 1 of 3 stages II-III cases was treated with cystectomy. Relatively high stage specific survival is experienced after cystectomy despite local recurrence in 1 of 5 patients.