- Email: [email protected]
Laparoscopic radical cystectomy and continent orthotopic ileal neobladder performed completely intracorporeally: the initial experience.1
164
William A. See / Urologic Oncology: Seminars and Original Investigations 21 (2003) 163–170
Sweden), and bladder wash cytology for new and recurrent bladder cancer. We examine whether tumor size, grade, and stage influence sensitivity and specificity of the markers. Materials and Methods: A total of 304 samples in 250 patients were studied. There were 174 patients who had a history of bladder cancer, including 93 with and 81 without recurrent tumor at cystoscopy. The other group of patients consisted of 66 with newly diagnosed bladder tumor and 64 investigated for microscopic hematuria that was found to be idiopathic. BTA stat was assayed according to manufacturer instructions. NMP22 and UBC were measured in urine with an enzyme-linked immunosorbent assay. A cutoff level of 4 for NMP22 and 1 for UBC was chosen to get the same specificity for new tumors as BTA stat (75%) Results: There was a highly significant difference (P ⬍ 0.001) in all markers between patients with new bladder tumors and those without. The difference was less pronounced for tumor recurrence for NMP22, UBC and BTA stat (p ⫽ 0.002, 0.016, and 0.244, respectively). The difference between new and recurrent tumors disappeared when corrected for tumor size, grade and stage. The sensitivity for new tumors was 65%, 75%, and 60% for NMP22, BTA stat, and UBC, respectively. Cytology had a sensitivity of 41% for new tumors at a specificity of 94%. The specificity for recurrence was 64% for NMP22, 54% BTA stat, and 72% UBC. The sensitivity was 45% for NMP22, 55% BTA stat, and 40% UBC. Conclusions: Tumor size, grade, and stage have a strong impact on sensitivity, and specificity for all three tested tumor markers as well as bladder wash cytology. The tumor markers or any combination of them cannot replace followup cystoscopy, mainly because most recurrences are small. The role of the markers for screening high risk populations and as a complement to follow-up cystoscopy remains to be evaluated.
Commentary Noninvasive, office-based, diagnostic tests have been widely marketed as replacements for, or adjuncts to, cystoscopy in the management of patients with transitional cell carcinoma of the urinary bladder. Although the concept of a sensitive, specific, noninvasive test to monitor disease status is laudable, we are simply “not there.” This article demonstrates that relative to their use at the time of initial diagnosis, in the follow-up setting the sensitivity and specificity of the currently available diagnostic tests is decreased. This decrease appears to at least in part be a consequence of the decreased tumor volume at the time of follow-up evaluation. As is aptly stated by Dr. deVere White in his editorial comment, at present “routine use of these markers with cystoscopy will add unreasonable expense without increasing diagnostic accuracy.” PII: S1078-1439(02)00284-3 William A. See, M.D
Laparoscopic radical cystectomy and continent orthotopic ileal neobladder performed completely intracorporeally: the initial experience. Gill IS, Kaouk JH, Meraney AM, Desai MM, Ulchaker JC, Klein EA, Savage SJ, Sung GT, Section of Laparoscopic and Minimally Invasive Surgery, Urological Institute, Cleveland Clinic Foundation, Cleveland, Ohio. J Urol 2002;168:13–18. Purpose: We introduce the operative technique of laparoscopic radical cystectomy and orthotopic ileal neobladder with a Studer limb performed completely intracorporeally. Materials and Methods: The procedure was performed in one man and one woman. Using a 6-port transperitoneal approach, radical cystectomy in the female patient and radical cystoprostatectomy in the male patient were completed laparoscopically with the urethral sphincter preserved. Bilateral pelvic lymphadenectomy was done. A 65-cm segment of ileum 15 cm from the ileocecal junction was isolated, and ileo-ileal continuity was restored using Endo-GIA staplers (U.S. Surgical, Norwalk, Connecticut). The distal 45 cm of the isolated ileal segment were detubularized, maintaining the proximal 10-cm segment intact as an isoperistaltic Studer limb. A globular shaped ileal neobladder was constructed and anastomosed to the urethra. Bilateral stented ureteroileal anastomoses were individually performed to the Studer limb. All suturing was done exclusively using free-hand laparoscopic techniques and the entire procedure was completed intracorporeally. An additional case is described of Indiana pouch continent diversion in which the pouch was constructed extracorporeally. Results: Total operative time for laparoscopic radical cystectomy and orthotopic neobladder was 8.5 and 10.5 hs, respectively, with a blood loss ranging from 200 to 400 cc. Hospital stay was 5 to 12 days and surgical margins of the bladder specimen were negative in each case. Both patients with orthotopic neobladder had complete daytime continence. Postoperative renal function was normal and excretory urography revealed unobstructed upper tracts. During followup ranging from 5 to 19 months one patient died of metastatic disease, whereas the other two are doing well without local or systematic progression. Conclusions: Laparoscopic radical cystectomy and orthotopic ileal neobladder performed completely intracorporeally are feasible.
Commentary The authors should be congratulated for this technical tour-de-force. Laparoscopic cystectomy with intracorporal construction of a continent orthotopic urinary diversion is perhaps the “last mountain” to be conquered in urologic laparoscopy. In the two highly selected patients presented, the procedure was performed in an acceptable period of time with minimal complications. Over time it has become increasingly clear that anything that can be done via an open surgical approach can potentially be done laparoscopically. A combination of determination, endurance, tenacity, and skill combine to make this feasible. The challenge for the future, however, is to continue to work to distinguish what can be done from what should be done. A clear definition of primary outcome end points
William A. See / Urologic Oncology: Seminars and Original Investigations 21 (2003) 163–170
165
relative to the disease in question should drive the above determination. In patients with cancer disease-free and overall survival must remain our primary endpoints. Until such data emerges these technological feats remain a “curiosity.” PII: S1078-1439(02)00285-5 William A. See, M.D
Long-term follow-up of G3T1 transitional cell carcinoma of the bladder treated with intravesical bacille Calmette-Gue´ rin: 18-year experience. Pansadoro V, Emiliozzi P, de Paula F, Scarpone P, Pansadoro A, Sternberg GN, Vincenzo Pansadoro Foundation, Rome, Italy. S. Giovanni Hospital, Rome, Italy. Urology 2002;59:227–231. Objectives: Immunotherapy with bacille Calmette–Gue´ rin (BCG) has been proposed in the past decade as first-line treatment for high-grade superficial bladder cancer (G3T1). We report our 18-year experience in the treatment of patients with G3T1 bladder cancer. Methods: From January 1989 to July 1997, 670 patients underwent transurethral resection for superficial bladder cancer. Eighty-one patients (12%) had G3T1 tumors. All of these patients were treated with an innovative schedule of Pasteur strain BCG followed by maintenance BCG therapy. Treatment consisted of four cycles of 6 instillations per cycle of BCG. The first cycle was administered weekly ⫻ 6, the second was given every 2 weeks ⫻ 6, the third cycle was given monthly ⫻ 6, and the fourth was given every 3 months ⫻ 6 instillations. Results: Sixty-nine patients (84%) completed at least the first two cycles. At a median follow-up of 76 months (range 30 to 197), the overall recurrence rate was 33% (27 of 81). The median time to recurrence was 20 months (range 5 to 128). Of these patients, 12 (15%) had progression at a median follow-up of 16 months (range 8 to 58). Cystectomy was required in seven patients (8%). Death from disease occurred in five (6%) of 81 patients. One patient died of adenocarcinoma at the ureterosigmoidostomy site. Sixty patients (74%) were alive at a median follow-up of 79⫹ months (range 15 to 182). Of these, 56 (69%) were alive with a functioning bladder. Conclusions: Conservative treatment with BCG is a reasonable approach for patients with primary G3T1 transitional cell carcinoma of the bladder. The long-term results of BCG therapy are good. Cystectomy may not be justified as the therapy of choice in first- line treatment of high-grade superficial carcinoma of the bladder.
Commentary G3T1 tumors constitute the most biologically aggressive group of tumors in the nonmuscle invasive category of bladder cancers. At present, there is some controversy regarding the role of BCG vs. immediate cystectomy in the management of this population. This report adds to a growing body of retrospective data suggesting that there are acceptable progression, survival, and bladder salvage rates using intravesical BCG. The authors of this trial used a novel maintenance schedule for these high-risk patients. Although intended to be administered in four cycles, only 84% of the patients completed the first two cycles. This finding parallels that of a growing anecdotal experience using the maintenance regime outlined in the recent SWOG trial. Maintenance, although perhaps more effective, is clearly associated with an increased burden of therapy and a relatively high incidence of noncompliance. Finally, despite BCG treatment efficacy in this population, long-term follow-up data suggests that they remain at high risk for disease progression. Early identification and aggressive management of nonresponders is critical for optimal outcome. PII: S1078-1439(02)00286-7 William A. See, M.D
Randomized study of single early instillation of (2R)-4-O-tetrahydropyranyl-doxorubicin for a single superficial bladder carcinoma. Okamura K, Ono Y, Kinukawa T, Matsuura O, Yamada S, Ando T, Fukatsu T, Ohno Y, Ohshima S, Members of Nagoya University Urological Oncology Group. Cancer 2002;94:363– 8. Background: Although transurethral resection of a bladder tumor (TUR-BT) alone has been standard treatment for single superficial bladder carcinoma, some authors reported a certain prophylactic effect of a single immediate intravesical instillation of chemotherapeutic agent after TUR-BT. A prospective randomized study was conducted to determine whether a single (2R)-4-O-tetrahydropyranyl-doxorubicin (THP) instillation immediately after TUR-BT is beneficial to patients with a single superficial bladder carcinoma. Methods: One hundred seventy patients with a single resectable superficial bladder carcinoma (Ta-1, primary or recurrent with no recurrence during the last 1 year) were enrolled in this study. THP (30 mg/30 mL of normal saline) was administered into the bladder within 6 hours after TUR-BT in arm A, whereas TUR-BT alone was done in arm B. Results: Of the 170 patients, 160 (94.1%) were eligible and were followed up for a median time of 40.8 months. There was a significant difference in the recurrence-free curve between the 2 arms (log-rank test; P ⫽ 0.0026), with 92.4% recurrence-free rate at 1 year, 82.7% at 2 years, and 78.8% at 3 years in arm A (84 patients) and 67.0%, 55.7%, and 52.6%, respectively, in arm B. The recurrence rate per year was 0.11 ⫾ 0.22 in arm A and 0.24 ⫾ 0.36 in arm B, with a significant difference (P ⫽ 0.007). Toxicity included pain with micturition in 9 patients (10.7%), urinary frequency/urgency in 5 patients (6.0%), and macroscopic hematuria in 7 patients (8.3%).
William A. See / Urologic Oncology: Seminars and Original Investigations 21 (2003) 163–170
Sweden), and bladder wash cytology for new and recurrent bladder cancer. We examine whether tumor size, grade, and stage influence sensitivity and specificity of the markers. Materials and Methods: A total of 304 samples in 250 patients were studied. There were 174 patients who had a history of bladder cancer, including 93 with and 81 without recurrent tumor at cystoscopy. The other group of patients consisted of 66 with newly diagnosed bladder tumor and 64 investigated for microscopic hematuria that was found to be idiopathic. BTA stat was assayed according to manufacturer instructions. NMP22 and UBC were measured in urine with an enzyme-linked immunosorbent assay. A cutoff level of 4 for NMP22 and 1 for UBC was chosen to get the same specificity for new tumors as BTA stat (75%) Results: There was a highly significant difference (P ⬍ 0.001) in all markers between patients with new bladder tumors and those without. The difference was less pronounced for tumor recurrence for NMP22, UBC and BTA stat (p ⫽ 0.002, 0.016, and 0.244, respectively). The difference between new and recurrent tumors disappeared when corrected for tumor size, grade and stage. The sensitivity for new tumors was 65%, 75%, and 60% for NMP22, BTA stat, and UBC, respectively. Cytology had a sensitivity of 41% for new tumors at a specificity of 94%. The specificity for recurrence was 64% for NMP22, 54% BTA stat, and 72% UBC. The sensitivity was 45% for NMP22, 55% BTA stat, and 40% UBC. Conclusions: Tumor size, grade, and stage have a strong impact on sensitivity, and specificity for all three tested tumor markers as well as bladder wash cytology. The tumor markers or any combination of them cannot replace followup cystoscopy, mainly because most recurrences are small. The role of the markers for screening high risk populations and as a complement to follow-up cystoscopy remains to be evaluated.
Commentary Noninvasive, office-based, diagnostic tests have been widely marketed as replacements for, or adjuncts to, cystoscopy in the management of patients with transitional cell carcinoma of the urinary bladder. Although the concept of a sensitive, specific, noninvasive test to monitor disease status is laudable, we are simply “not there.” This article demonstrates that relative to their use at the time of initial diagnosis, in the follow-up setting the sensitivity and specificity of the currently available diagnostic tests is decreased. This decrease appears to at least in part be a consequence of the decreased tumor volume at the time of follow-up evaluation. As is aptly stated by Dr. deVere White in his editorial comment, at present “routine use of these markers with cystoscopy will add unreasonable expense without increasing diagnostic accuracy.” PII: S1078-1439(02)00284-3 William A. See, M.D
Laparoscopic radical cystectomy and continent orthotopic ileal neobladder performed completely intracorporeally: the initial experience. Gill IS, Kaouk JH, Meraney AM, Desai MM, Ulchaker JC, Klein EA, Savage SJ, Sung GT, Section of Laparoscopic and Minimally Invasive Surgery, Urological Institute, Cleveland Clinic Foundation, Cleveland, Ohio. J Urol 2002;168:13–18. Purpose: We introduce the operative technique of laparoscopic radical cystectomy and orthotopic ileal neobladder with a Studer limb performed completely intracorporeally. Materials and Methods: The procedure was performed in one man and one woman. Using a 6-port transperitoneal approach, radical cystectomy in the female patient and radical cystoprostatectomy in the male patient were completed laparoscopically with the urethral sphincter preserved. Bilateral pelvic lymphadenectomy was done. A 65-cm segment of ileum 15 cm from the ileocecal junction was isolated, and ileo-ileal continuity was restored using Endo-GIA staplers (U.S. Surgical, Norwalk, Connecticut). The distal 45 cm of the isolated ileal segment were detubularized, maintaining the proximal 10-cm segment intact as an isoperistaltic Studer limb. A globular shaped ileal neobladder was constructed and anastomosed to the urethra. Bilateral stented ureteroileal anastomoses were individually performed to the Studer limb. All suturing was done exclusively using free-hand laparoscopic techniques and the entire procedure was completed intracorporeally. An additional case is described of Indiana pouch continent diversion in which the pouch was constructed extracorporeally. Results: Total operative time for laparoscopic radical cystectomy and orthotopic neobladder was 8.5 and 10.5 hs, respectively, with a blood loss ranging from 200 to 400 cc. Hospital stay was 5 to 12 days and surgical margins of the bladder specimen were negative in each case. Both patients with orthotopic neobladder had complete daytime continence. Postoperative renal function was normal and excretory urography revealed unobstructed upper tracts. During followup ranging from 5 to 19 months one patient died of metastatic disease, whereas the other two are doing well without local or systematic progression. Conclusions: Laparoscopic radical cystectomy and orthotopic ileal neobladder performed completely intracorporeally are feasible.
Commentary The authors should be congratulated for this technical tour-de-force. Laparoscopic cystectomy with intracorporal construction of a continent orthotopic urinary diversion is perhaps the “last mountain” to be conquered in urologic laparoscopy. In the two highly selected patients presented, the procedure was performed in an acceptable period of time with minimal complications. Over time it has become increasingly clear that anything that can be done via an open surgical approach can potentially be done laparoscopically. A combination of determination, endurance, tenacity, and skill combine to make this feasible. The challenge for the future, however, is to continue to work to distinguish what can be done from what should be done. A clear definition of primary outcome end points
William A. See / Urologic Oncology: Seminars and Original Investigations 21 (2003) 163–170
165
relative to the disease in question should drive the above determination. In patients with cancer disease-free and overall survival must remain our primary endpoints. Until such data emerges these technological feats remain a “curiosity.” PII: S1078-1439(02)00285-5 William A. See, M.D
Long-term follow-up of G3T1 transitional cell carcinoma of the bladder treated with intravesical bacille Calmette-Gue´ rin: 18-year experience. Pansadoro V, Emiliozzi P, de Paula F, Scarpone P, Pansadoro A, Sternberg GN, Vincenzo Pansadoro Foundation, Rome, Italy. S. Giovanni Hospital, Rome, Italy. Urology 2002;59:227–231. Objectives: Immunotherapy with bacille Calmette–Gue´ rin (BCG) has been proposed in the past decade as first-line treatment for high-grade superficial bladder cancer (G3T1). We report our 18-year experience in the treatment of patients with G3T1 bladder cancer. Methods: From January 1989 to July 1997, 670 patients underwent transurethral resection for superficial bladder cancer. Eighty-one patients (12%) had G3T1 tumors. All of these patients were treated with an innovative schedule of Pasteur strain BCG followed by maintenance BCG therapy. Treatment consisted of four cycles of 6 instillations per cycle of BCG. The first cycle was administered weekly ⫻ 6, the second was given every 2 weeks ⫻ 6, the third cycle was given monthly ⫻ 6, and the fourth was given every 3 months ⫻ 6 instillations. Results: Sixty-nine patients (84%) completed at least the first two cycles. At a median follow-up of 76 months (range 30 to 197), the overall recurrence rate was 33% (27 of 81). The median time to recurrence was 20 months (range 5 to 128). Of these patients, 12 (15%) had progression at a median follow-up of 16 months (range 8 to 58). Cystectomy was required in seven patients (8%). Death from disease occurred in five (6%) of 81 patients. One patient died of adenocarcinoma at the ureterosigmoidostomy site. Sixty patients (74%) were alive at a median follow-up of 79⫹ months (range 15 to 182). Of these, 56 (69%) were alive with a functioning bladder. Conclusions: Conservative treatment with BCG is a reasonable approach for patients with primary G3T1 transitional cell carcinoma of the bladder. The long-term results of BCG therapy are good. Cystectomy may not be justified as the therapy of choice in first- line treatment of high-grade superficial carcinoma of the bladder.
Commentary G3T1 tumors constitute the most biologically aggressive group of tumors in the nonmuscle invasive category of bladder cancers. At present, there is some controversy regarding the role of BCG vs. immediate cystectomy in the management of this population. This report adds to a growing body of retrospective data suggesting that there are acceptable progression, survival, and bladder salvage rates using intravesical BCG. The authors of this trial used a novel maintenance schedule for these high-risk patients. Although intended to be administered in four cycles, only 84% of the patients completed the first two cycles. This finding parallels that of a growing anecdotal experience using the maintenance regime outlined in the recent SWOG trial. Maintenance, although perhaps more effective, is clearly associated with an increased burden of therapy and a relatively high incidence of noncompliance. Finally, despite BCG treatment efficacy in this population, long-term follow-up data suggests that they remain at high risk for disease progression. Early identification and aggressive management of nonresponders is critical for optimal outcome. PII: S1078-1439(02)00286-7 William A. See, M.D
Randomized study of single early instillation of (2R)-4-O-tetrahydropyranyl-doxorubicin for a single superficial bladder carcinoma. Okamura K, Ono Y, Kinukawa T, Matsuura O, Yamada S, Ando T, Fukatsu T, Ohno Y, Ohshima S, Members of Nagoya University Urological Oncology Group. Cancer 2002;94:363– 8. Background: Although transurethral resection of a bladder tumor (TUR-BT) alone has been standard treatment for single superficial bladder carcinoma, some authors reported a certain prophylactic effect of a single immediate intravesical instillation of chemotherapeutic agent after TUR-BT. A prospective randomized study was conducted to determine whether a single (2R)-4-O-tetrahydropyranyl-doxorubicin (THP) instillation immediately after TUR-BT is beneficial to patients with a single superficial bladder carcinoma. Methods: One hundred seventy patients with a single resectable superficial bladder carcinoma (Ta-1, primary or recurrent with no recurrence during the last 1 year) were enrolled in this study. THP (30 mg/30 mL of normal saline) was administered into the bladder within 6 hours after TUR-BT in arm A, whereas TUR-BT alone was done in arm B. Results: Of the 170 patients, 160 (94.1%) were eligible and were followed up for a median time of 40.8 months. There was a significant difference in the recurrence-free curve between the 2 arms (log-rank test; P ⫽ 0.0026), with 92.4% recurrence-free rate at 1 year, 82.7% at 2 years, and 78.8% at 3 years in arm A (84 patients) and 67.0%, 55.7%, and 52.6%, respectively, in arm B. The recurrence rate per year was 0.11 ⫾ 0.22 in arm A and 0.24 ⫾ 0.36 in arm B, with a significant difference (P ⫽ 0.007). Toxicity included pain with micturition in 9 patients (10.7%), urinary frequency/urgency in 5 patients (6.0%), and macroscopic hematuria in 7 patients (8.3%).