Matrix metalloproteinase-9 expression in bladder washes from bladder cancer patients predicts pathological stage and grade.

The matrix metalloproteinases (MMPs), in particular the gelatinases (MMP-2 and MMP-9) have been associated with tumor cell invasion and metastasis in many human cancers. Here we examined the expression of proMMP-2 (gelatinase A) and proMMP-9 (gelatinase B) proteins in the cellular component of bladder washes obtained from 65 patients. Twenty-six patients had active bladder cancer, 24 had a history of bladder cancer but no evidence of active disease at the time of cystoscopy (recurrence-free), and 15 patients had lesions other than bladder cancer (controls). The results were correlated with the cytological findings of the bladder wash and the histopathological results of the tumor resection when performed. In patients with active transitional cell carcinoma of the bladder, 71 and 38% had expression and overexpression of the latent form of MMP-9 (proMMP-9), respectively. In contrast, neither latent nor active MMP-2 could be detected in any of the samples examined, regardless of tumor status. Overexpression of proMMP-9 correlated with higher grade (P = 0.003) and pathological stage (P = 0.04) of disease in the active bladder cancer group. No significant gelatinase expression was detected in the recurrence-free and control cases. Compared with urine cytology, proMMP-9 expression had an overall higher sensitivity for bladder cancer identification (71 versus 54%, P = 0.11). Detection of proMMP-9 in bladder washes may be a novel approach for the identification of patients with more aggressive forms of bladder cancer.

Grading the invasive component of urothelial carcinoma of the bladder and its relationship with progression-free survival.

Although grading is valuable prognostically in pTa and pT1 papillary urothelial carcinoma, it is unclear whether it provides any prognostic information when applied to the invasive component in muscle-invasive carcinoma. The authors analyzed 93 cases of muscle-invasive urothelial carcinoma of the bladder treated with radical cystectomy for which follow-up information was available. Each case was graded using the Malmström grading system for urothelial carcinoma, applied to the invasive component. Pathologic stage, lymph node status, and histologic invasion pattern were also recorded and correlated with progression-free survival. Thirty-four cases (37%) were pT2, 40 (43%) were pT3, and 19 (20%) were pT4. Of the 77 patients who had a lymph node dissection at the time of cystectomy, 34 (44%) had metastatic carcinoma to one or more lymph nodes. The median survival for pT2, pT3, and pT4 stages was 85, 24, and 29 months, respectively (p = 0.0001). Lymph node-negative and lymph node-positive patients had a median survival of 63 and 23 months, respectively (p = 0.0001). Fifteen patients (16%) were graded as 2b and 78 patients (84%) were graded as 3. Median survival of patients graded as 2b was 34 months compared with 31 months for patients graded as 3 (p value not significant). Three invasive patterns were recognized: nodular (n = 13, 14%), trabecular (n = 39, 42%), and infiltrative (n = 41, 44%). The presence of any infiltrative pattern in the tumor was associated with a median survival of 29 months, compared with 85 months in tumors without an infiltrative pattern (p = 0.06). Pathologic T stage and lymph node status remain the most powerful predictors of progression in muscle-invasive urothelial carcinoma. In this group of patients histologic grade, as defined by the Malmström system and as applied to the invasive component, provided no additional prognostic information. An infiltrative growth pattern may be associated with a more dismal prognosis.

Impact of location and multifocality of positive surgical margins on disease-free survival following radical prostatectomy: a comparison between African-American and white men.

OBJECTIVES: Although the rate of positive surgical margins is higher in African-American men (AAM) than in white men (WM), the impact of this difference on survival is not clear. Furthermore, it is unknown whether there are racial differences in the distribution of the positive surgical margins after radical retropubic prostatectomy (RRP). We investigated the differences between AAM and WM in terms of the site and multifocality of the positive surgical margins and their effect on disease-free survival (DFS) following RRP. METHODS: Between January 1991 and December 1995, 493 patients (288 WM and 205 AAM) were treated with RRP as monotherapy. Positive surgical margins were observed in 179 patients (86 WM and 93 AAM). Patients were divided in two groups: group 1 = WM and group 2 = AAM. The incidence and location of the positive surgical margins and their correlation with DFS were determined and compared. RESULTS: Overall, AAM had a higher rate of positive surgical margins than WM (48% versus 33%, respectively, P = 0.001). There was no significant difference in the frequency of multifocality of the positive margins (P = 0.4). Positive surgical margins were located significantly more often at the base in AAM (P = 0.015); however, the location of the positive surgical margins did not impact on DFS between groups. In those with multifocal positive surgical margins, AAM had a worse DFS compared with WM (P = 0.03). CONCLUSIONS: Race is an independent prognostic factor for DFS in patients with positive surgical margins. There were no differences in DFS between WM and AAM based on the margin location. In WM, prognostic factors for DFS in those with positive surgical margins were preoperative serum prostate-specific antigen, Gleason score, and pathologic stage. Conversely, in AAM none of these parameters were significant predictors of failure.

Predictors for maximal outcome in patients undergoing salvage surgery for radio-recurrent prostate cancer.

OBJECTIVES: To determine preradiation and preoperative clinical staging and postoperative pathologic factors that can predict disease-free survival in patients undergoing salvage surgery for radio-recurrent prostate cancer. METHODS: A retrospective review was performed on 40 patients who underwent salvage surgery for radio-recurrent prostate cancer. Preradiation and preoperative clinical staging factors, as well as pathologic stage were analyzed as predictors of disease-free survival. Biochemical failure was defined as a persistent serum prostate-specific antigen (PSA) elevation greater than 0.4 ng/mL. RESULTS: As a group, salvage surgery provided excellent clinical disease control in 35 of 40 patients (87.5%). Overall, 18 of 38 (47.4%) patients analyzed had no evidence of biochemical progression. Preradiation clinical stage and pathologically organ-confined disease were statistically significant predictors of disease-free survival (P = 0.03 and P = 0.02, respectively). Seminal vesicle invasion and positive lymph nodes were the worst pathologic prognostic factors. Preoperative clinical T1c disease approached statistical significance in predicting pathologically organ-confined disease and disease-free survival (P = 0.08 and P = 0.07, respectively). CONCLUSIONS: Ideal candidates for salvage surgery should have preradiation and preoperative clinically organ-confined disease. All patients with pathologically organ-confined disease following salvage prostatectomy were disease free at a mean follow-up of 36.1 months. Salvage surgery, although technically feasible, should not be widely advocated as an effective curative treatment in patients with locally advanced disease at the time of diagnosis.

Salvage surgery or salvage radiotherapy for locally recurrent prostate cancer.

OBJECTIVES: To evaluate the efficacy and toxicity of salvage radiation or surgery for locally recurrent tumor after initial treatment for clinically localized prostate cancer. METHODS: The treatment records of 70 patients with local treatment failure after definitive therapy for clinically localized prostate cancer were reviewed. Initial treatment consisted of external beam radiation therapy (RT) in 27 patients and radical retropubic prostatectomy (RP) in 43 patients. RESULTS: The mean serum PSA levels were similar in both groups before initial treatment: 8.5 and 10.5 ng/mL for the salvage RP and salvage RT groups, respectively (P = 0.09). However, at the time of salvage treatment, the mean serum PSA levels were 9.1 and 1.1 ng/mL for the salvage RP and salvage RT groups, respectively (P = 0.0001). The mean time from tumor recurrence to salvage treatment was 15.6 months for the salvage RP group and 4.9 months for the salvage RT group (P = 0.0001 ). Although there was no statistical difference in the disease-free survival rate (P = 0.38), a trend for better disease control in the salvage RT group was evident (74.4% versus 44.4%). Patients treated with salvage RP had a higher rate of urinary incontinence than those undergoing salvage RT: 63% and 32.6%, respectively (P = 0.01). CONCLUSIONS: The disease-free survival rate was similar between patients receiving salvage RP or RT, despite the significantly higher serum PSA levels at the time of treatment and the delay in time to treatment for the salvage RP patients. Salvage RP is associated with a high rate of urinary incontinence. Earlier identification of tumor recurrence after RT may improve the efficacy and safety of salvage RP.

Management of primary urethral cancer.

OBJECTIVES: To determine the best therapeutic approach for treatment of patients with urethral cancer according to tumor location and clinical-pathologic stage. METHODS: A retrospective review of 21 consecutive patients diagnosed with primary urethral carcinoma was performed. Clinical-pathologic staging, treatment modality, and outcome were analyzed. RESULTS: The overall survival rate was 62%. In patients with clinical Stage Ta-2N0M0 tumors, 8 of 9 patients (89%) are free of disease compared to 5 of 12 patients (42%) with Stage T3-4N0-2M0 tumors (P = 0.03). Best treatment outcome for patients with Stage T3 disease or higher was obtained when multimodality therapy (neoadjuvant chemotherapy and radiation therapy with or without surgery) was administered, with a disease-free survival rate of 60%. CONCLUSIONS: Clinical-pathologic stage was a strong predictor of disease-free survival rate. For patients with Ta-2N0M0 tumors, multimodality therapy may not be required. Conversely, best treatment outcomes in patients with T3-4N0-2M0 tumors are obtained by administering a multimodal therapy combining chemotherapy and radiation therapy with surgical resection.

Primary adenocarcinoma of the urethra with metastasis to the glans penis: successful treatment with chemotherapy and radiation therapy.

Primary carcinoma of the male urethra accounts for less than 1% of malignancies in males. A 54-year-old man with primary adenocarcinoma of the urethra with metastasis to the glans penis and lymphadenopathy in the right groin was treated successfully by combined chemotherapy (5-fluorouracil and cis-platinum) and external beam radiotherapy (total dose of 75 Gy). Short-term remission using multimodal approach with penile preservation was achieved in the present case.

Treatment outcome after radical prostatectomy is not adversely affected by a pre-existing penile prosthesis.

OBJECTIVES: To report on the safety of radical retropubic prostatectomy (RRP) in patients with a penile prosthesis presenting with clinically localized prostate cancer. METHODS: From January 1990 to December 1997, 8 consecutive men with a penile prosthesis underwent RRP for clinically localized prostate cancer. Retrospective data regarding patient population, operating time, estimated blood loss, length of hospital stay, and clinical outcome were evaluated. RESULTS: Mean patient age was 65.4 years (range 57 to 70) at the time of RRP, with a mean preoperative serum prostate-specific antigen level of 11.5 ng/mL. Mean duration of RRP surgery was 183.9 minutes, and the mean estimated blood loss was 1281.8 mL. No complication requiring penile prosthesis removal occurred. In 1 case, the reservoir tubing was punctured during closure of the abdominal fascia wall. This was immediately recognized and fixed. All patients had a functioning penile prosthesis after RRP. CONCLUSIONS: RRP can be safely and expeditiously performed in patients with a pre-existing penile prosthesis. The risk of prosthesis malfunction after RRP is very low. Patients with a penile prosthesis and prostate cancer should not be denied the option of undergoing RRP.

Assessment of psychosexual adjustment after insertion of inflatable penile prosthesis.

OBJECTIVES: To evaluate the psychosexual benefit obtained from multicomponent penile implant surgery in patients with erectile dysfunction. METHODS: A psychosexual questionnaire was given to 35 patients undergoing penile prosthesis implantation before surgery and at 3 months, 6 months, and 1 year after surgery. The questionnaire consisted of 13 questions scored on a scale from 1 through 5. Results of the questionnaire were statistically analyzed for differences among the preoperative, 3-month postoperative, 6-month postoperative, and 1-year postoperative period. RESULTS: The general linear model evaluation showed a significant difference for each overall combination of the following pairs: preoperative versus 3 months postoperative (P=0.0005) and 3 months postoperative versus 6 months postoperative (P=0.002). There was no overall difference between psychosexual total score at 6 months after surgery and 1 year after prosthesis implantation (P=0.85). The patients perceived improvement in their erectile ability and libido. Concern about obtaining and maintaining an erection during intercourse was significantly alleviated. There was an increase in the frequency of sexual activity and an improvement in satisfaction with sex life. A decrease in feelings of sadness, depression, anxiety, anger, frustration, and embarrassment related to sexual activity was also noted. CONCLUSIONS: The current study demonstrates significant improvement in the psychosexual well being of multicomponent penile implant recipients, with attainment of a high level of patient satisfaction up to 1 year after surgery.

Lymph node size does not correlate with the presence of prostate cancer metastasis.

OBJECTIVES: To determine whether lymph node size is a surrogate marker for lymph node metastasis. METHODS: We reviewed 980 patients who underwent radical retropubic prostatectomy with bilateral pelvic lymph node dissection for clinically localized prostate cancer, of whom 63 had lymph node metastases. A comparable group of patients with prostate cancer undergoing radical prostatectomy who did not have lymph node involvement was identified using the following parameters: serum prostate-specific antigen level, clinical and pathologic stage, and pre- and postoperative Gleason score. The axial and longitudinal dimensions of the nodes from patients with and without metastases were analyzed to assess the significance of lymph node size in predicting the presence of metastases. All patients had negative preoperative computed tomography (CT) and bone scans. Of the 63 patients with lymph node metastases, 48 had tissue available for measuring the dimensions of the lymph nodes. RESULTS: A total of 76 metastatic and 92 negative lymph nodes were identified from the patients with and without metastatic nodes, respectively. The mean nodal longitudinal size was 1.65 cm (range 0.2 to 6.5) and 3.50 cm (range 0.5 to 9) for positive and negative nodes, respectively (P = 0.0001). The mean axial nodal size was 0.8 cm (range 0.2 to 3.2) and 1.0 cm (range 0.2 to 2.2) for positive and negative lymph nodes, respectively. In 56 metastatic nodes (74%), the axial size was less than 1 cm and in 20 (26%) less than 5 mm. CONCLUSIONS: Lymph node size should not be used as a surrogate for the presence of lymph node metastases. Although no patient had enlarged lymph nodes by CT scan criteria (greater than 1.5 cm), 6 (8%) of 48 and 19 (12%) of 48 patients with and without lymph node metastases, respectively, had nodes with an axial dimension greater than 1.5 cm.

Should Gleason score 7 prostate cancer be considered a unique grade category?

OBJECTIVES: To evaluate pathologic characteristics and biochemical survival rate differences between patients with Gleason score 6 or less, 7, and 8 or more prostate cancer. METHODS: A total of 652 patients who underwent a radical prostatectomy for clinically localized prostate cancer between March 1991 and December 1995 were selected for this study. Patients who underwent neoadjuvant or adjuvant hormonal therapy or radiotherapy were excluded. Clinical and pathologic data were obtained from our prostate cancer data base. Serum prostate-specific antigen (PSA) level, pathologic stage, and disease-free survival (DFS) were analyzed between the three Gleason score groups. RESULTS: The overall mean pretreatment serum PSA level was 12.9 ng/mL, being 8.4, 13.4, and 23 ng/mL for Gleason score 6 or less, 7, and 8 or more prostate cancers, respectively (P = 0.0001). Of patients with specimen Gleason score 6 or less, 7, and 8 or more, pathologic organ-confined disease was present in 69.4%, 43.1 %, and 9.2%, respectively (P = 0.001). Extraprostatic extension was present in 30.6%, 56.9%, and 90.8% (P = 0.0001); positive surgical margins, considered independently from the other pathologic findings, were present in 31 %, 47.6%, and 67.8% of patients with Gleason score 6 or less, 7, and 8 or more, respectively (P = 0.0001). DFS was 34.5% for patients with Gleason score 8 or more, 75% for Gleason score 7, and 91.2% for Gleason score 6 or less prostate cancers, at a median follow-up of 34.2 months (P = 0.0001). On multivariable analysis, after adjusting for serum PSA level (10 or less or more than 10 ng/mL) and pathologic stage, Gleason score (6 or less, 7, 8 or more) remained a statistically significant predictor of DFS (P = 0.0001). CONCLUSIONS: Patients with Gleason score 7 prostate cancer should be considered a specific prognostic category. We believe that this distinction is critical to obtain more reliable results from prostate cancer analyses about prognosis of patients treated with curative intent.

Urinary diversion-related outcome in patients with pelvic recurrence after radical cystectomy for bladder cancer.

OBJECTIVES: To evaluate the impact of urinary diversion on disease status, complications, and subsequent treatment in patients with pelvic tumor recurrence after radical cystectomy for bladder cancer. METHODS: A retrospective review of 201 consecutive cases of radical cystectomy for bladder cancer, performed at our institution between March 1991 and March 1996, identified 33 patients (16.4%) with disease recurrence in the pelvis with or without systemic metastasis. Urinary diversion in patients with tumor recurrence was an ileal conduit, continent cutaneous diversion, or orthotopic neobladder in 19, 3, and 11 patients, respectively. The mean follow-up for all patients undergoing cystectomy was 25.9 months (range 8 to 75). The mean time to diagnosis of local disease recurrence after cystectomy was 13.9 months (range 5 to 50). RESULTS: In 21 (63.6%) of 33 patients, pelvic recurrence and systemic metastasis were present simultaneously. Disease recurrence was associated with poor outcome: only 8 patients (24.2%) were alive and disease free, 7 of whom had isolated local recurrence without evidence of systemic metastasis. There was no difference in overall survival or type of therapy delivered once disease recurrence was diagnosed between patients with an orthotopic neobladder and those with a cutaneous (continent or incontinent) urinary diversion. The only diversion-related complication resulting from pelvic recurrence was 1 case of tumor invasion into an orthotopic neobladder, requiring conversion to an ileal conduit. CONCLUSIONS: The type of urinary diversion did not impact a patient's risk of complications, the ability to receive salvage treatment, or overall survival once pelvic recurrence was diagnosed. Patients at high risk of pelvic recurrence should not be excluded from receiving an orthotopic urinary diversion.

[Role of partial nephrectomy in the treatment of kidney cancer]. / La place de la néphrectomie partielle dans le traitement des cancers du rein.

Incidental finding of small renal carcinoma by radiologic exams (ultrasound, computed tomography, MRI) performed for non urological purposes raises therapeutic and management problems (therapeutic abstinence and surveillance, partial or radical nephrectomy). Radical nephrectomy is recognized as a curative treatment for renal cell carcinoma. However, partial nephrectomy was suggested for renal cell carcinoma of solitary functional kidney or bilateral tumors in order to avoid dialysis or renal transplantation. The debate remains open for the small renal carcinomas with a normal controlateral kidney. Is partial nephrectomy an adequate treatment or rather perform radical nephrectomy? The present study was performed to analyse the published literature on the subject.

[Contribution of surgical techniques used in liver transplantation in the treatment of retroperitoneal tumors]. / Apport des techniques chirurgicales utilisées en transplantation hépatique pour traiter les tumeurs du rétropéritoine.

The authors describe the surgical technique used in liver transplantation and its application to treat retroperitoneal tumours. This technique comprises primary mobilization of the liver with easy vascular control. This technique, used in 29 patients, is simple, facilitates exposure of great vessels which can be controlled and allows excellent exposure in difficult cases. Analysis of the postoperative course emphasized the absence of hepatic and renal complications, as reflected by normal renal function and liver enzymes. The use of this technique for renal and adrenal surgery avoids the need for extracorporeal circulation and a thoracophrenoabdominal approach, thereby limiting the specific complications related to these two procedures.

[Acute urinary retention secondary to clear cell adenocarcinoma of the urethra]. / Rétention urinaire aiguë secondaire à un adénocarcinome à cellules claires de l'urèthre.

The authors report a case of primary clear cell cancer of the urethra in a woman presenting with acute urinary retention. The diagnosis was based on cystoscopy and confirmed by histological examination of urethral biopsies. Treatment consisted of urethrocystectomy with creation of an "Indiana pouch". The pathological stage was T3N2M0 [1]. Three months postoperatively, the patient presented with inguinal lymph node metastases. She was treated with 3 courses of chemotherapy (mitomycin and 5-fluorouracil) combined with radiotherapy. With a follow-up of 10 months, the patient is still alive and inguinal lymph nodes have regressed. This case report emphasizes the rarity of this histological type and describes the management of urinary retention in a woman when an underlying specific disease is suspected.

[Treatment of colo-vesical fistulas in one-stage operation]. / Le traitement des fistules colo-vésicales en un seul temps opératoire.

OBJECTIVES: To evaluate the results of one-stage surgical treatment of colo-vesical fistulas. MATERIAL AND METHODS: 24 patients (16 males and 8 females) were treated for colo-vesical fistula by this technique. Sigmoid diverticulosis represented the commonest aetiology. In our study, cystoscopy was the most useful modality for the diagnosis of fistula. RESULTS: No deaths and no recurrent fistulas were observed. However, one case of peritonitis secondary to dehiscence of the colo-colonic anastomosis in a patient suffering from Crohn's disease and two wall abscesses in diabetic patients were observed. CONCLUSION: The morbidity and mortality rates after one-stage treatment of colo-vesical fistulas were low. This method not only improves the patient's quality of life, but is also less expensive, by avoiding a second hospitalisation and can be proposed as first-line treatment.

[Primary small cell carcinoma of the bladder]. / Les cancers primitifs à petites cellules de la vessie.

OBJECTIVES: Primary small cell carcinomas of the bladder differ from transitional cell carcinomas by their rarity, histological characteristics, malignant potential and treatment. This study analysed the diagnostic criteria and therapeutic results obtained in a consecutive patient series over a 6-year period. MATERIALS AND METHODS: 7 patients (6 men and one woman) suffering from primary small cell carcinoma of the bladder were evaluated. Histological slides, treatment modalities and duration of survival were reviewed. RESULTS: The commonest clinical presentation was macroscopic haematuria. All tumours were invasive at the time of diagnosis. Two patients were treated by partial cystectomy, one of whom also received adjuvant chemotherapy. One patient was treated by radical cystectomy and 4 also received adjuvant chemotherapy, including 2 with neoadjuvant radiotherapy at a dosage of 65 Gy. The three patients treated by a single treatment modality (surgery alone or chemotherapy alone) had a shorter survival, in contrast with patients treated by a combination of chemotherapy and/or surgery. CONCLUSION: Primary small cell carcinomas of the bladder are rare and have a poor prognosis. Treatment must consist of a combination of neoadjuvant or adjuvant chemotherapy and surgery or radiotherapy to achieve the best results.

Current concepts in androgen deprivation therapy--is there a "best" endocrine treatment?

Androgen deprivation therapy has become the mainstay treatment for locally advanced and metastatic prostate cancer. Castrate testosterone levels can be achieved by a multitude of treatments. We performed a medline literature search to answer the question, is there a "best" endocrine treatment? In conclusion we found that the "best" endocrine therapy for advanced prostate cancer is complete androgen blockade (CAB) with a luteinizing hormone-releasing hormone (LHRH) agonist and a nonsteroidal antiandrogen.

Collagen injection in the management of post-radical prostatectomy intrinsic sphincteric deficiency.

Transurethral injection of collagen is a minimally invasive option for the treatment of urinary incontinence secondary to intrinsic sphincteric deficiency (ISD). We report on the results of transurethral injection in 21 men with urinary incontinence secondary to ISD. Twenty-one consecutive men with a mean age of 69.5 years (range, 51-84), with ISD documented by demonstrating urinary leakage with Valsalva maneuver on physical examination and by video-urodynamic studies were treated with transurethral collagen injection. The etiologies of the incontinence were radical retropubic prostatectomy (RRP) in seven (33.3%), RRP followed by external radiation therapy in seven (33.3%), and transurethral resection of the prostate (TURP) with subsequent RRP in seven (33. 3%). The mean total volume of collagen injected per patient was 18.4 mL (range, 1-44.5). The average number of injections was 2.9 (range, 1-5). The mean follow-up was 12.5 months (range, 1-39). One (5%) patient became dry, 12 (57%) had significant improvement, and eight (38%) had no change. Overall pad use decreased from 2.5 pads/day to 1.68 pads/day, before and after collagen injection (P = 0.014). No difference in outcomes was demonstrated in African American men versus Caucasian American men (P = 0.38), age (<65 and >65 years, P = 0.88), presence of erectile dysfunction, or duration of incontinence (<20 or >20 months, P = 0.71). There were no reported complications. Collagen injection has minimal morbidity and is a viable option for improving incontinence status in men. Neither age, race, erectile function, nor duration of incontinence appears to affect treatment outcome. Neurourol. Urodynam. 18:653-658, 1999.