Laparoscopic-Assisted Nephroureterectomy after Radical Cystectomy for Transitional Cell Carcinoma

Objective: To report our experience with laparoscopic-assisted nephroureterectomy for upper tract transitional cell carcinomas after radical cystectomy and urinary diversion. Materials and Methods: Seven patients (53-72 years-old) underwent laparoscopic-assisted nephroureterectomy 10 to 53 months after radical cystectomy for transitional cell carcinoma at our institution. Surgical technique, operative results, tumor features, and outcomes of all patients were retrospectively reviewed. Results: Mean operative time was 305 minutes with a significant amount of time spent on the excision of the ureter from the urinary diversion. Estimate blood loss and length of hospital stay averaged 180 mL and 10.8 days, respectively. Intraoperative and postoperative complications occurred in two patients each. There was one conversion to open surgery. Pathology confirmed upper-tract transitional cell carcinoma in all cases. Metastatic disease occurred in two patients after a mean follow-up of 14.6 months. Conclusions: Nephrouretectomy following cystectomy is a complex procedure due to the altered anatomy and the presence of many adhesions. A laparoscopic-assisted approach can be performed safely in properly selected cases but does not yield the usual benefits seen with other laparoscopic renal procedures.


INTRODUCTION
Nephroureterectomy (NU) is the treatment of choice for high grade, invasive, or recurrent transitional cell carcinoma (TCC) of the upper urinary tract (UUT).Since the first laparoscopic NU was performed in 1991, (1) several series have demonstrated the safety and efficacy of the procedure, (2)(3)(4)(5)(6) with the benefits of decreased hospitalization, return to activity and pain requirement.Nephroureterectomy following cystectomy is a very complex procedure due to the need for complete ureterectomy in the presence of many adhesions and an altered anatomy.This requires extensive enterolysis and dissection in a previously operated site to allow for removal of the ureter from the urinary diversion.There is limited data on open removal and no published data on laparoscopic NU for UUT TCC following cystectomy and urinary diversion.The objective of this study is to report our experience with laparoscopic-assisted NU for UUT TCC after radical cystectomy.

MATERIALS AND METHODS
In 2003 and 2005, seven patients previously treated with radical cystectomy underwent laparoscopic-assisted NU for UUT TCC.Individual characteristics of the patients and the features of the primary bladder tumors are summarized in Tables-1 and 2, respectively.Cystectomy was performed for BCG-refractory carcinoma in situ (CIS) of the urinary bladder in four patients, recurrent superficial high grade TCC in two, and muscle-invasive disease in one.
Evaluation after cystectomy consisted of physical examination, chest X-ray, and urine cytology every 3-4 months in the first and second years, and at 6-month intervals for up to 5 years, followed by yearly exams.The upper tract was surveyed by intravenous urography (IVU), computed tomography (CT), conduitography and retrograde pyelography, and/or conduitoscopy and ureteroscopy every 6-12 months in the first year, and then yearly or when clinically indicated.Patients with a suspected upper tract tumor were biopsied, and in highly suspicious cases in which retrograde ureteroscopy was not possible were evaluated through nephroscopy, and antegrade pyelography and ureteroscopy.
Indications for NU in patients with a normal contralateral kidney included high-grade biopsyproven TCC recurrences in three patients, and   persistent positive urinary cytologies in two patients -one who was non-responsive and another who recurred after mitomycin.Two patients had solitary kidneys.The first had been submitted to laparoscopic NU before radical cystectomy for primary UUT TCC, and developed contralateral UUT recurrence in a nonfunctioning renal unit.The second developed bilateral, extensive disease, not amenable to conservative resection, and underwent open NU followed by contralateral laparoscopic NU.Laparoscopic-assisted NU was performed in all patients using a transperitoneal approach.Pneumoperitoneum was achieved through a Veress needle placed lateral to the rectus abdominalis, away from the lower midline incision.The Visiport optical trocar (United States Surgical Corporation, USSC, Norwalk, CT, USA) was used for initial access to the abdomen.Local adhesions from previous surgery were carefully taken down with sharp dissection.The colon was then mobilized medially and the kidney removed in a standard laparoscopic fashion (6).In summary, a plane was created between the ureter and the aorta or the vena cava (for left and right-side NU respectively), and this was carried up to the renal hilum.The renal artery and vein were dissected and sequentially transected with the use of an endovascular GIA stapler (USSC, Norwalk, CT, USA).The adrenal gland was routinely spared by entering the Gerota's fascia and dissecting it off the upper pole of the kidney.The remaining of the dissection was carried outside Gerota's fascia.Following complete dissection of the kidney and upper ureter, dissection of the remaining ureter was carried down as far distally as possible.On the left side, the ureter was dissected to the area where the ureter traversed the mesentery of the sigmoid colon.On the right, the dissection usually approached the urinary diversion.A low abdominal incision (in the previous cystectomy incision site) was then made when the complexity of the dissection was beyond the limitations of a safe laparoscopic approach.The ureteroenteric anastomosis was identified and completely excised with a cuff of normal bowel mucosa.The urinary diversion was closed with running 3-0 polyglactin suture, and repositioned in its usual anatomic position.In the two cases with solitary kidney, urinary diversion was removed en bloc with the kidney and ureter.
Operative results and outcomes of all patients treated by this technique were retrospectively reviewed and analyzed.

RESULTS
Five male and two female patients with a median age of 68 years (range 53 to 72 years) developed multifocal recurrent UUT TCC after treatment with radical cystectomy for bladder cancer.The features of these recurrences are shown in Table-3.
All patients required extensive lysis of adhesions due to the previous open surgery, and multiple prior ureteroscopies and biopsies.One of the patients could not have his entire kidney dissected laparoscopically due to a prior abdominal aortic aneurysm repair that resulted in a fibrotic reaction around the renal hilum.The midline incision was extended and the renal dissection was completed though the extended open incision.
No intraoperative complications from the laparoscopic procedure occurred.Two patients had intraoperative complications during the open stage of the procedure, due to the intense adjacent reactive process.The first had an inadvertent bowel injury, which was managed with segmental enterectomy.In the second patient, transection of the contralateral ureter was recognized intraoperatively, requiring reanastomosis to the ileal conduit.
All patients had delayed return to bowel function beyond three days.Other minor postoperative complications occurred in two patients.One had colonic pseudo-obstruction that resolved with conservative management, and the other presented with a superficial wound infection treated with intravenous antibiotics.Two other patients developed anticipated end-stage renal disease due to previous contralateral NU.They were started on hemodialysis and required longer hospitalizations due to instituting dialysis in the setting of no renal function.
The mean operative time was 305.6 minutes (range 220 to 360 minutes), and estimate blood loss  was, in average, 180 mL (range 100 to 250 mL).Mean length of hospital stay was 10.8 days (range 5 to 25 days).Follow-up averaged 14.6 months (range 2 to 22 months), although two patients were lost to followup.The remaining five patients were regularly followed-up for more than 12 months.Table-4 gives an overview of the outcomes from each of the cases studied.

COMMENTS
TCC is a multifocal disease affecting the entire urothelium (7,8) and subsequent tumors may occur anywhere in the urinary tract after initial diagnosis (9).While primary UUT TCC is frequently followed by bladder recurrences, (7,10) and the cumulative incidence of UUT recurrence after bladder cancer is up to 28% in five years, (11) the incidence of UUT tumors after radical cystectomy is low (7)(8)(9).The incidence of post-cystectomy UUT TCC differs according to the stage of the bladder tumor.Patients submitted to radical cystectomy for superficial disease have a higher probability of developing UUT tumors than those with muscle-invasive disease (8).Other risk factors responsible for UUT recurrences in these patients include histological grade, presence of distal ureteric carcinoma at cystectomy, associated CIS, multifocality, and involvement of the prostatic urethra (8,9,12).
The optimum method of surveillance of the UUT after cystectomy is questionable.Various regimens with annual or biannual imaging (IVU or CT), combined with urine cytology, have been reported (9).Since six (85.7%) of our patients had distal ureteral involvement by CIS or TCC, we adopted a more aggressive surveillance, similar to that for superficial bladder tumors, with urine cytology, imaging studies, and UUT endoscopy.
The role of urinary cytology in the diagnosis of UUT TCC is controversial, in particular for patients with intestinal diversions, because of the presence of small bowel cells (7).However, since most UUT TCC after cystectomy tends to be high grade, sensitivity is higher in these patients (9).Obtaining urine using ureteral catheterization further improves the diagnostic yield (13). IVU and CT scans increase the likelihood of early detection, and help in management decisions, but the key role in the diagnosis of recurrent UUT TCC is retrograde pyelography and ureteroscopy with biopsy, with a reported accuracy of 94% (13).(2)(3)(4)(5)(6)8,14) and it is equally effective in terms of oncological outcome.(2)(3)(4)(5)14) Following this trend, after performing over 80 laparoscopic NU at our department, we started performing laparoscopicassisted NU for recurrent UUT TCC post-radical cystectomy in 2003.Surgical technique mirrors traditional open NU, including the removal of a cuff of bowel at the ureteroenteral anastomosis.All except one patient had the renal portion of the procedure successfully accomplished laparoscopically, and all surgeries were completed through the same previous incision performed for radical cystectomy, including the patient that required open conversion for marked hilar vessels fibrosis.In this patient, the incision was extended to the xiphoid process.
Mean operative time was long compared to standard NU but this was not due to the laparoscopic nephrectomy portion of the procedure but rather the complex dissection of the urinary diversion and necessity for complete removal of the ureter with a cuff of the bowel.In all cases, extensive and tedious lysis of adhesions was necessary to release the diversion and distal ureter from adjacent bowel.It is not surprising that delayed recovery of bowel function was seen in these patients, resulting in a lengthened hospital stay when compared to NU with no prior cystectomy.In addition, 2 patients had solitary kidneys removed and subsequently required postoperative dialysis, which made management and hospitalization more complex.These patients had failed prior attempts at organ sparing therapy.
The outcome of patients who develop UUT TCC after cystectomy is usually poor (1,7,12).So far, two of our patients presented recurrences, although the median follow-up is still limited.In addition, these patients are at higher risk of TCC in remaining sites due to the multifocal nature of their disease.Lifelong surveillance for recurrent disease in remaining urothelial surfaces and distant sites is necessary.

CONCLUSIONS
Our experience confirms that NU for UUT TCC after radical cystectomy is a complex procedure due to the altered anatomy and the presence of many adhesions.In the present series, a laparoscopicassisted approach could be performed safely in properly selected cases but did not yield the usual benefits of decreased hospitalization seen with other laparoscopic renal procedures mainly due to patient co-morbidities and the delayed return to bowel function.We even still prefer this approach, as after many years of experience the majority of our surgeons regularly performing renal surgery feel more comfortable with the laparoscopic approach to the kidney.The distal ureter and bowel cuff, however, must still be extracted with open surgery.We recognize that advanced laparoscopic experience is required to achieve even comparable results to an open approach in this technically demanding procedure.

EDITORIAL COMMENT
Radical cystectomy with extended lymph node dissection is the gold standard treatment for invasive and/or refractory superficial bladder cancer (1).Although upper tract recurrence after radical cystectomy has a low incidence at 2% to 4%, it is associated with poor prognosis, and a short survival

Table 4 -
Oncological outcomes after laparoscopic-assisted NU for recurrent UUT TCC. of care for high grade and stage UUT lesions has been open NU, with removal of a cuff of bladder around the ureteral orifice.(2-6,12-14)Several centers have replaced the open surgery for laparoscopic NU, given that it has well established advantages compared to the open approach,

Table 1 -
Epidemiologic and clinical features of the patients.

Table 2 -
Characteristics of bladder tumors treated with radical cystectomy.

Table 3 -
Clinical-pathological features of upper urinary tract recurrences after radical cystectomy.