Prevention and Management of Complications Following Radical Cystectomy for Bladder Cancer

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1 EUROPEAN UROLOGY 57 (2010) available at journal homepage: Collaborative Review Bladder Cancer Prevention and Management of Complications Following Radical Cystectomy for Bladder Cancer Nathan Lawrentschuk a, *, Renzo Colombo b, Oliver W. Hakenberg c, Seth P. Lerner d, Wiking Månsson e, Arthur Sagalowsky f, Manfred P. Wirth g a Division of Urology, Department of Surgical Oncology, Princess Margaret Hospital, University of Toronto, Toronto, Canada b Department of Urology, University Vita-Salute - San Raffaele Hospital, Milan, Italy c Department of Urology, Rostock University, Rostock, Germany d Scott Department of Urology, Baylor College of Medicine, Houston, Texas, USA e Department of Urology, Ska ne University Hospital, Lund, Sweden f Department of Urology, University of Texas Southwestern Medical Center, Dallas, Texas, USA g Department of Urology, University Hospital Carl Gustav Carus, Technical University of Dresden, Dresden, Germany Article info Article history: Accepted February 17, 2010 Published online ahead of print on February 26, 2010 Keywords: Bladder carcinoma Cystectomy Adverse effects Urology Surgery Review Abstract Context: This review focuses on the prevention and management of complications following radical cystectomy (RC) for bladder cancer (BCa). Objective: We review the current literature and perform an analysis of the frequency, treatment, and prevention of complications related to RC for BCa. Evidence acquisition: A Medline search was conducted to identify original articles, reviews, and editorials addressing the relationship between RC and short- and long-term complications. Series examined were published within the past decade. Large series reported on multiple occasions (Lee [1], Meyer [2], and Chang and Cookson [3]) with the same cohorts are recorded only once. Quality of life (QoL) and sexual function were excluded. Evidence synthesis: The literature regarding prophylaxis, prevention, and treatment of complications of RC in general is retrospective, not standardised. In general, it is of poor quality when it comes to evidence and is thus difficult to synthesise. Conclusions: Progress has been made in reducing mortality and preventing complications of RC. Postoperative morbidity remains high, partly because of the complexity of the procedures. The issues of surgical volume and standardised prospective reporting of RC morbidity to create evidence-based guidelines are essential for further reducing morbidity and improving patients QoL. # 2010 European Association of Urology. Published by Elsevier B.V. All rights reserved. * Corresponding author. University of Toronto, Surgical Oncology, 610 University Ave, Ste 3-130, Princess Margaret Hospital, Toronto, M5G2M9 Canada. address: lawrentschuk@gmail.com (N. Lawrentschuk). 1. Introduction Radical cystectomy (RC) with pelvic lymph node dissection provides the best cancer-specific survival for muscleinvasive urothelial cancer [2,3] and is the standard treatment, with 10-yr recurrence-free survival rates of 50 59% and overall survival rates of around 45% [2,4]. RC with urinary diversion (UD) is a procedure in which reduction of morbidity, rapid postoperative rehabilitation, limited length of hospital stay, and cost containment are /$ see back matter # 2010 European Association of Urology. Published by Elsevier B.V. All rights reserved. doi: /j.eururo

2 984 EUROPEAN UROLOGY 57 (2010) Table 1 Large series of radical cystectomy with reported early postoperative complications ( ) Series (past decade, around 100 patients) Summary Shabsigh et al, 2009 [13] Novara, 2009 [16] Boström et al, 2009 [123] Meyer et al, 2009 [2] Nieuwenhuijzen et al, 2008 [46] Patients Study period Centres Single Single Single Multi (3) Single Mortality at 30 d * Minor complications Major complications One postoperative complication or more (67 in hospital, % postdischarge) Operating time, h (IC), (neo), 5.6 (CCD) EBL Intraoperative transfusion rate (U) and perioperative * * (in 82%) Medical DVT PE Septicaemia Acute respiratory distress Pneumonia Failure to wean from ventilator/on ventilator >48 h postoperatively PE; clinical evidence of PE Reintubation for arrest; unplanned intubation for cardiac or pulmonary arrest Cardiac (general) MI Dysrhythmia; postoperative cardiac arrhythmia Cardiac arrest; initiation of advanced cardiac life support Enterocolitis/persistent diarrhoea Acute renal failure; worsening renal function 0 7 requiring dialysis or ultrafiltration UTI Pyelonephritis Metabolic imbalance (severe)/delirium Skin ulcer/pressure sore PEG leakage Stroke (neurologic) Surgical Perioperative blood transfusion rate Postoperative haemorrhage; transfusion >4 U after operation 72 h postop Subileus (paralytic) Constipation GI (eg, emesis, gastritis, ulcer) Small bowel obstruction Enteroanastomosis leak Required TPN y GI bleed Pyrexia of unknown origin Pelvic lymphocoele with intervention Pelvic lymphocoele (no intervention) Percutaneous drainage Peritonitis Wound infection, including superficial (incisional) Deep (fascial/muscle) wound infections Wound dehiscence Secondary healing With revision Pelvic haematoma Pelvic/abdominal abscess Without revision With revision Diversion related 0 16

3 EUROPEAN UROLOGY 57 (2010) Table 1 (Continued ) Series (past decade, around 100 patients) Summary Shabsigh et al, 2009 [13] Novara, 2009 [16] Boström et al, 2009 [123] Meyer et al, 2009 [2] Nieuwenhuijzen et al, 2008 [46] Urine leak/pouch leak/other urine related Stomal necrosis/stricture Diversion necrosis Rectal injury Fistula Reoperation rate Other IC = EBL = estimated blood loss; DVT = deep vein thrombosis; PE = pulmonary embolism; MI = myocardial infarction; UTI = urinary tract infection; PEG = percutaneous endoscopic gastrostomy; GI = gastrointestinal; TPN = total parenteral nutrition. * 90-d morbidity and mortality. y Given to all participants as protocol. difficult to achieve [5]. Prior to 1990, large series (100 patients) reported mortality of % and early morbidity of 28 42% [6 10]. In the past decade, mortality has been reduced to 0 3.9%, while early morbidity remains at 11 68% (Tables 1 4). Reported late complications in contemporary series are 19 58% (Table 5). The difficulties with comparing morbidity across series and time periods are manifold. The reduction in perioperative mortality probably reflects improvements in multidisciplinary management as well as in the management of early complications Large series of radical cystectomy reporting on complications When considering large series (100 patients) of RC that report on short- and long-term complications, one must state at the outset that the patients form an extremely heterogeneous group. Reporting of complications is not standardised, few series are prospective, differing surgical techniques are utilised, patients selection is not uniform, length of follow-up is inconsistent, classification of complications varies (eg, early vs late, at least four different definitions exist for ileus), and the metachronous nature of the series makes comparison extremely difficult. Clearly, larger prospective series with longer follow-up are need to be published. Because of the aforementioned limitations, this review can only provide suggestions based on everyday clinical practice rather than recommendations based on evidence-based medicine unless otherwise indicated in the text Reporting of complications for cystectomy Donat argues that the disparity in the quality of surgical complication reporting in urologic oncology makes it impossible to compare the morbidity of surgical techniques and outcomes [11]. Terms such as major and minor complication have little meaning, particularly if not clearly defined or consistent. The lack of standardisation is hampering the progress of improving morbidity and mortality associated with RC [4,12 14]. Attempts have been made to correct these deficiencies in urologic oncology reporting in prospective studies. First, Hollenbeck et al [15] accessed the Veterans Affairs National Surgical Quality Improvement Program (NSQIP) data set, which has the advantages of a large sample size, multi-institutional participation, prospective explicit data collection by trained nurse reviewers, and a reliable assessment of 30-d postoperative follow-up. It should be highlighted that in their series, they specifically did not report on complications with an incidence of < 0.5%. Second, Shabsigh et al [13] and Novara et al [16] have utilised complication grading systems based on the Clavien system in order to assist in standardising complication reporting in solid organ transplants [17]. Such methodology identifies 11 specific categories, and five grades and may be adapted to any urologic oncology procedure [11]. Ultimately, standard guidelines for accruing and reporting surgical morbidity data as well as defining procedure-specific complications with minimal follow-up of reconstructions and severity grading need to be established for RC [11,14,18]. 2. Patient selection and its influence on complications and outcome 2.1. Patient selection and timing of cystectomy Patient comorbidities Increasing age and being female affect morbidity [13,19 21]. However, the old adage that definitive therapy based on physiologic age as opposed to chronologic age remains true [22], with the key being patient selection in addition to adequate preoperative counselling and risk balancing [20]. Disappointingly, many large series of RC do not comprehensively report on patient comorbidities (eg, only providing the American Society of Anaesthesiologists score) [13]. Where reported, having more than two comorbidities appears detrimental [23]. In general, although RC after pelvic radiation therapy (RT) is associated with acceptable morbidity, the risk of complications requiring invasive intervention is increased (eg, pelvic collections) [24]. Conversely, others have indicated that postirradiation complications do not increase [25]. Although prior RT should not be a significant factor in bowel segment selection, it is still a factor and at minimum, a careful visual inspection of the bowel is required [26].

4 986 EUROPEAN UROLOGY 57 (2010) Table 2 Large series of radical cystectomy with reported early postoperative complications ( ) Series (past decade, around 100 patients) Summary Maffezzini et al, 2008 [5] Arumainayagamet et al, 2008 [25] Pycha et al, 2008 [124] Lowrance et al, 2008 [125] Novotny et al, 2007 [126] Patients Study period N/A Centres Single Single Single Single Single Mortality at 30 d Minor complications Major complications One postoperative complication or more Operating time, h EBL (median) 1208 Intraoperative transfusion rate, U * 38 * N/A Medical DVT PE Septicaemia Acute respiratory distress Pneumonia Failure to wean from ventilator/on ventilator >48 h postoperatively PE; clinical evidence of PE Reintubation for arrest; unplanned intubation for cardiac or pulmonary arrest Cardiac (general) MI Dysrhythmia; postoperative cardiac arrhythmia Cardiac arrest; initiation of advanced cardiac life support Enterocolitis/persistent diarrhoea Acute renal failure; worsening renal function requiring dialysis or ultrafiltration UTI Pyelonephritis Metabolic imbalance (severe)/delirium Skin ulcer/pressure sore PEG leakage Stroke (neurologic) Surgical Perioperative blood transfusion rate Postoperative haemorrhage; 0 9 transfusion >4 U after operation 72 h postop Subileus (paralytic) Constipation 0 12 GI (eg, emesis, gastritis, ulcer) Small bowel obstruction Enteroanastomosis leak Required TPN GI bleed Pyrexia of unknown origin Pelvic lymphocoele with intervention Pelvic lymphocoele (no intervention) Percutaneous drainage Peritonitis Wound infection, including superficial (incisional) Deep (fascial/muscle) wound infections Wound dehiscence Secondary healing With revision Pelvic haematoma Pelvic/abdominal abscess Without revision With revision Diversion related 0 16 Urine leak/pouch leak/other urine related Stomal necrosis/stricture Diversion necrosis Rectal injury Fistula

5 EUROPEAN UROLOGY 57 (2010) Table 2 (Continued ) Series (past decade, around 100 patients) Summary Maffezzini et al, 2008 [5] Arumainayagamet et al, 2008 [25] Pycha et al, 2008 [124] Lowrance et al, 2008 [125] Novotny et al, 2007 [126] Reoperation rate Other N/A = not applicable; EBL = estimated blood loss; DVT = deep vein thrombosis; PE = pulmonary embolism; MI = myocardial infarction; UTI = urinary tract infection; PEG = percutaneous endoscopic gastrostomy; GI = gastrointestinal; TPN = total parenteral nutrition. * Perioperative. Table 3 Large series of radical cystectomy with reported early postoperative complications ( ) Series (past decade, around 100 patients) Summary Studer et al, 2006 [117] Konety et al, 2006 [127] Hollenbeck et al, 2005 [19] Clark et al, 2005 [22] Knap et al, 2004 [128] Lee et al, 2004 [1] Patients Study period Centres Single Multiple/ Multi (123) Single Single Single population based Mortality at 30 d Minor complications Major complications One postoperative complication or more Operating time, h EBL Intraoperative transfusion rate, U Medical DVT PE 0 6 < Septicaemia Acute respiratory distress N/A Pneumonia Failure to wean from ventilator/on ventilator >48 h postoperatively PE; clinical evidence of PE Reintubation for arrest; unplanned intubation for cardiac or pulmonary arrest Cardiac (general) MI Dysrhythmia; postoperative cardiac arrhythmia Cardiac arrest; initiation of advanced cardiac life support Enterocolitis/persistent diarrhoea Acute renal failure; worsening renal function requiring dialysis or ultrafiltration UTI Pyelonephritis Metabolic imbalance (severe)/delirium Skin ulcer/pressure sore PEG leakage Stroke (neurologic) Surgical Perioperative blood transfusion rate Postoperative haemorrhage; transfusion >4 U after operation 72 h postop Subileus (paralytic) Constipation 0 12 GI (eg, emesis, gastritis, ulcer) Small bowel obstruction 0 7 (Included with ileus) Enteroanastomosis leak Required TPN GI bleed Pyrexia of unknown origin Pelvic lymphocoele with intervention Pelvic lymphocoele (no intervention) Percutaneous drainage 0 2.7

6 988 EUROPEAN UROLOGY 57 (2010) Table 3 (Continued ) Series (past decade, around 100 patients) Summary Studer et al, 2006 [117] Konety et al, 2006 [127] Hollenbeck et al, 2005 [19] Clark et al, 2005 [22] Knap et al, 2004 [128] Lee et al, 2004 [1] Peritonitis Wound infection, including superficial (incisional) Deep (fascial/muscle) wound infections Wound dehiscence Secondary healing With revision Pelvic haematoma Pelvic/abdominal abscess Without revision With revision Diversion related Urine leak/pouch leak/other urine related Stomal necrosis/stricture Diversion necrosis Rectal injury Fistula Reoperation rate 0 17 Other EBL = estimated blood loss; DVT = deep vein thrombosis; PE = pulmonary embolism; N/A = not applicable; MI = myocardial infarction; UTI = urinary tract infection; PEG = percutaneous endoscopic gastrostomy; GI = gastrointestinal; TPN = total parenteral nutrition. A special subset includes patients previously treated with RT and/or radical prostatectomy (RP), who may have a greater level of morbidity than previously reported [27]. Prior abdominal or pelvic surgery is also considered a risk factor for complications [13]. Finally, extravesical disease, which occurs in many large series in around 25% of cases [15] as well as cystectomy with palliative intent [28,29] or salvage situation [30] are risk factors for morbidity. Increased body mass index is also associated with an increased risk of wound infection and dehiscence as well as hernias [16,25]. In general, one should not consider obesity or previous pelvic RT a contraindication for RC. The construction of a diversion or orthotopic bladder substitution is, however, not that easy in the very obese. We suggest that only experienced urologists perform RC in such patients because the additional risks for bleeding, urinary tract infection (UTI), and reliability of UD Timing of cystectomy and perioperative chemotherapy Although the timing of RC generally relates to oncologic outcome only [31], data on morbidity and the use of multimodal therapy are becoming relevant. For example, it is advisable to leave the catheter during chemotherapy with continent diversions in order to reduce toxicity from the reabsorption of the drugs [32]. The impact of early morbidity from RC in potentially delaying receipt of adjuvant chemotherapy in 30% of patients has recently been reported [33]. Conversely, data from RC series with neoadjuvant chemotherapy suggest that it does not increase postoperative morbidity [13,25]. volume is emerging [34 37]. Both the mortality [34 36] and morbidity [38] of RC are reduced in higher-volume centres [37]. Individual surgeon volume is also a significant predictive factor for complications [39]. However, some smaller centres (<13 RC/yr) believe that they can still achieve acceptable results [23]. The Calman-Hine report requires that patients have access to a uniformly high quality of care for maximal possible cure rates and quality of life [40]. Bladder cancer treatment should therefore be completed in reference centres with expertise in major urologic oncology with appropriate intensive care and interventional radiologists. As several retrospective studies have clearly demonstrated a relationship among complications, mortality, and surgical volume [37,41], itisinouropinion inevitable that the urologic community should ultimately agree on a recommendation for a minimum surgical volume for RC and do so before health care providers take this issue out of our hands. Clearly, this is a complex issue that depends not only on the surgeon s personal experience but also on many other factors. In our opinion, an annual rate of 10 RC procedures per hospital seems adequate, with patients scheduled to undergo continent reconstruction, such as orthotopic bladder substitution or continent cutaneous diversion, being referred to large units. 3. Surgical technique and complications 3.1. Patient preparation: preoperative factors, fast-track surgery, and technique 2.2. Surgical relationship of morbidity to surgeon and hospital volume A whole body of literature concerning the surgical learning curve and the personal as well as institutional surgical Preoperative factors Preoperative renal failure is a significant risk factor and should be corrected prior to RC [19], occasionally necessitating preoperative nephrostomy. Surgical morbidity is not increased if the serum creatinine <2.5 mg/dl [33].

7 Table 4 Large series of radical cystectomy with reported early postoperative complications ( ) Series (past decade, around 100 patients) Summary Kulkarni et al, 2003[129] Chahal et al, 2003 [130] Cookson et al, 2003 [3] Malavaud et al, 2001 [131] Dahm, et al, 2001 [54] Rosario et al, 2000 [132] Hautmann et al, 1999 [133] Patients Study period N/A Centres Single Multicentre Single Multi (2) Single 101, single centre Single centre Mortality at 30 d * 3 y Minor complications N/A Major complications N/A One postoperative complication or more Operating time, h N/A EBL N/A Intraoperative transfusion rate, U z Medical DVT (includes PE) PE Septicaemia Acute respiratory distress Pneumonia Failure to wean from ventilator/on ventilator >48 h postoperatively PE; clinical evidence of PE Reintubation for arrest; unplanned intubation for cardiac or pulmonary arrest Cardiac (general) MI Dysrhythmia; postoperative cardiac arrhythmia Cardiac arrest; initiation of advanced cardiac life support Enterocolitis/persistent diarrhoea Acute renal failure; worsening renal function requiring dialysis or ultrafiltration UTI Pyelonephritis Metabolic imbalance (severe)/delirium 0 4 Skin ulcer/pressure sore PEG leakage Stroke (neurologic) Surgical Perioperative blood transfusion rate Postoperative haemorrhage; transfusion 0 9 >4 U after operation 72 h postop Subileus (paralytic) Constipation 0 12 GI (eg, emesis, gastritis, ulcer) Small bowel obstruction Enteroanastomosis leak Required TPN GI bleed Pyrexia of unknown origin EUROPEAN UROLOGY 57 (2010)

8 990 Table 4 (Continued ) Series (past decade, around 100 patients) Summary Kulkarni et al, 2003[129] Chahal et al, 2003 [130] Cookson et al, 2003 [3] Malavaud et al, 2001 [131] Dahm, et al, 2001 [54] Rosario et al, 2000 [132] Hautmann et al, 1999 [133] Pelvic lymphocoele with intervention Pelvic lymphocoele (no intervention) Percutaneous drainage Peritonitis Wound infection, including superficial (incisional) Deep (fascial/muscle) wound infections Wound dehiscence Secondary healing 0 8 With revision 0 5 Pelvic haematoma Pelvic/abdominal abscess Without revision With revision Diversion related 0 16 Urine leak/pouch leak/other urine related Stomal necrosis/stricture Diversion necrosis Rectal injury Fistula 0 4 Reoperation rate Other N/A = not applicable; EBL = estimated blood loss; DVT = deep vein thrombosis; PE = pulmonary embolism; N/A = not applicable; MI = myocardial infarction; UTI = urinary tract infection; PEG = percutaneous endoscopic gastrostomy; GI = gastrointestinal; TPN = total parenteral nutrition. * 60-d morbidity and mortality. y 90-d morbidity and mortality. z Perioperative. EUROPEAN UROLOGY 57 (2010)

9 Table 5 Large series of radical cystectomy with reported late operative complications Summary Nieuwenhuijzen et al, 2008 [46] Meyer et al, 2008 [2] Studer et al, 2006 [117] Clark et al, 2005 [27] Madersbacher et al, 2003 [109] Chahal et al, 2003 [130] Kulkarni et al, 2003 [129] Hautmann et al, 1999 [134] Late complications >30 d >30 d >30 d >90 d >90 d >90 d N/A >90 d Patients Follow-up, yr N/A 7.3 Single N/A Complication rate Surgery related Conversion to conduit UTI Reservoir related Diversion related (unspecified) Incisional hernia Pouch stones Pyelonephritis Dehydration Intestinal obstruction Parastomal hernia Stomal stenosis Stomal hernia Stomal other Ureteroileal/ureteroenteric stenosis Enterourethral stricture/urethral stricture Lymphocoele Enteric fistula Abscess Pelvic abscess Vaginal prolapse/cystocoele Severe hydronephrosis/ureteric reflux Urolithiasis Metabolic, including vitamin B 12 deficiency Bowel obstruction (conservative) Bowel obstruction (surgery) Not surgery related GI (general) Renal insufficiency * 27 3 Diarrhoea Infectious Neurologic Pulmonary Haematologic Cardiovascular Other N/A = not applicable; UTI = urinary tract infection; GI = gastrointestinal. * Renal related. EUROPEAN UROLOGY 57 (2010)

10 992 EUROPEAN UROLOGY 57 (2010) Patients with severe nutritional depletion may receive hyperalimentation prior to RC to reduce complications [42], butlittlesupportivedataexist[5] Technical surgical considerations Preoperative consideration for the type of UD is essential, taking into account patient factors such as previous abdominal surgery, RT, and overall health and function [43]. The neobladder as an orthotopic bladder substitute approaches the ideal UD by providing a low-pressure, easily emptied continent reservoir; it preserves the upper tracts and avoids the body image issues of a stoma [44]. Caveats usually imposed on patient selection for orthotopic bladder substitution include metastatic disease, tumour involvement at the bladder neck or urethra in women, and prostate involvement in men [45,46]. Additionally, an ileal conduit is generally advised to all patients with compromised renal function or electrolyte disturbance [43], elderly patients, those with significant comorbidities or preexisting bowel disease, and those who are unable to perform intermittent catheterisation or have severe functional impairment, with consultation between the urologist and enterostomal therapist being essential [44,46 48]. Thus, ileal conduits remain the most common form of diversion worldwide, with orthotopic bladder diversions increasing each year. The expected rate of complications according to the different surgical solutions after RC are analysed in Tables 1 5. We realise that the reporting is so variable that it cannot be shown that one surgical solution provides fewer complications than another other. From a technical point of view, two major factors have positively affected the postoperative complication rate: the improved understanding of surgical anatomy of the pelvis (ie, accurate control of the dorsal vein, helping to reduce blood loss) [49] and the advances and implementations in surgical instrumentation (ie, bipolar diathermy and staplers) Anaesthesia and perioperative assistance Anaesthesia and perioperative assistance are certainly contributing factors to the overall reduction in mortality during the past decade [50]. Preoperative anaesthetic assessment clinics (eg, cardiac testing) with correction of modifiable medical disease (eg, hypertension, cardiac arrhythmias) have assisted in this regard [15,50,51]. Further, the introduction of complementary epidural anaesthesia in major surgery has favourably affected perioperative complications. In a randomised series of 50 patients [52], combined epidural and general anaesthesia was associated with significantly lower intraoperative blood loss compared to general anaesthesia alone. Also, mandatory surgical intensive care unit admission is probably no longer necessary [53,54], with adequate recovery room observation [34,55], invasive blood pressure monitoring [51], and tailored fluid replacement the key to reducing morbidity [56] Fast-track surgery Enhanced recovery protocols with standardised perioperative plan of care or fast-track (FT) approaches have emerged as tools to assist RC patients [5]. The general principles of FT protocols in visceral surgery incorporate innovative aspects of analgesia, bowel preparation, feeding, and drainage management. In one study examining traditional versus FT surgery, no increase in the amount of complications including digestive complications could be observed in the FT group. Moreover, the postoperative stay in the intermediate care unit was significantly shorter in the FT cohort, and feeding was completed significantly earlier [57]. Controlled clinical trials are needed to further investigate additional aspects of an FT regime for RC (eg, antibiotic regimen, earlier removal of catheters). The use of bowel preparation to reduce the incidence of postoperative ileus has not been established [58,59]. Non-narcotic analgesics and early institution of an oral diet appear to be promising implementations of the FT approach and deserve to be investigated in multicentre studies [60] Bowel preparation Bowel preparation may be used, particularly when the large bowel is utilised for reconstruction to reduce contamination. In general surgery, a recent trend has been for no preparation; but in such cases, there is no urinary tract anastomosis to bowel mucosa. If small bowel only is being used, there is scant evidence to support bowel preparation [59] Laparoscopic and robot-assisted techniques Recently, there has been a rapid rise in the interest in and application of minimally invasive techniques (laparoscopic or robotic) RC [61 67]. However, the data are premature and from comparatively small series Perioperative and postoperative complications Postoperative complications and some suggestions for their prevention and treatment according to the current literature are summarised for early and late complications Perioperative complications Blood loss and transfusions. Acute blood loss is common in RC, and predicting blood loss and transfusion requirements remains difficult. In RC, most blood loss occurs when dealing with the bladder vasculature and pedicles. One prospective, randomised trial of 70 patients found that the estimated blood loss (523 ml vs 756 ml, on average) and transfusion requirements were significantly reduced by using a stapler device instead of the traditional sutureligation technique for the dissection of the bladder [68]. Meticulous intraoperative haemostasis is important, as is refinement in surgical techniques in order to decrease blood loss [23]. Certainly, the anatomical understanding of RP has contributed to a reduction in blood loss (eg, dorsal venous plexus ligation) [69]. Patient selection and combined epidural and general anaesthesia may act to lower transfusion rates, but larger studies are required [52] (Table 6).

11 EUROPEAN UROLOGY 57 (2010) Table 6 Recommendations for prevention and treatment of blood loss and blood transfusion Blood loss (mean loss: cm 3 ) and blood transfusion (1 9%) Use meticulous technique/dissection. Use controlled hypotensive anaesthesia. Take your time. Use haemostatic surgery devices such as bipolar devices (eg, LigaSure), harmonic scalpel, or stapling devices. Use oxidised cellulose (Surgicel) or absorbable gelatine sponge (Gelfoam) on raw surfaces. Use adhesive/biologic tissue glue (Tisseel or FloSeal), if appropriate. Ensure adequate intravascular filling with or without haemodilution. Transfuse if haemoglobin is between 7 and 8 g/dl or if clinically indicated Urinary extravasation/reservoir leak. Prevention involves leaving drains until the surgeon is satisfied that anastomotic integrity is ensured as well as avoiding selfcatheterisation or aggressive catheterisation. Catheters in orthotopic bladder substitutes and pouches should be free of mucous build-up [70], while urinary stents may be irrigated if external [71]. Stents may be attached to the Foley catheter with a nylon suture, facilitating a wet pouch and ease of stent removal, with the Foley adequately fixed to prevent dislodgement. The need for an additional suprapubic catheter for orthotopic bladder substitutions or pouch diversion in case the main catheter becomes blocked is controversial, with little evidence available. It is common practice to use urinary stents for 10 d with no imaging unless clinically indicated prior to removal [72]. In a randomised, controlled trial of 54 patients, stenting of the ureteroileal anastomosis allowed for significantly less frequent incidence of early postoperative pelvicaliceal system dilatation, a quicker return of bowel activity, and a reduced incidence of metabolic acidosis [73]. Surgeon preference and experience will dictate how long drains and catheters are left in place. For example, in orthotopic bladder substitutes/continent diversion, the transurethral catheter may be removed in d without a pouchogram if the drain output is minimal say, 50 ml/d while others do routine pouchograms to detect a leak before catheter removal [16,74]. Memorial Sloan-Kettering Cancer Centre has even challenged the use of stents in RC reconstructions (Table 7) Sepsis, urinary tract infection, and pneumonia. Perioperative antimicrobial prophylaxis (AMP) to prevent surgical site infections (wound, peritoneum, urinary tract, bowel) for RC patients has been routinely used for decades [75], but there is no clear evidence that it is actually necessary, and nor has the best schedule been defined [76,77]. AMP (eg, cephalosporin and metronidazole) should be given prior to opening the bowel. Evidence to support longer courses is lacking, with a single AMP dose possibly being adequate [76]. Pulmonary physiotherapy with intensive spirometry contributes to reducing postoperative pneumonia after abdominal surgery. The value of optimised pain alleviation and mobilisation should be evaluated in prospective trials [78] (Table 8) Deep vein thrombosis and pulmonary embolism. Risk factors for deep vein thrombosis (DVT) include age >40 yr, obesity, malignancy, recent surgery, prior history of pulmonary embolism (PE) or DVT, and pelvic lymphocoeles or haematomas [79]. Prophylactic treatment in patients undergoing radical pelvic surgery can reduce the risk of DVT from 30% to 10% and that of fatal PE from 5% to 0.4% [80]. Low-molecular-weight heparins are currently the gold standard prevention agent [81], with intermittent pneumatic compression stockings (IPCS) also being effective [82]. Graduated compression stockings should be combined with heparin/icps for prophylaxis [83] (Table 9) Paralytic ileus. Ileus is a general term used to describe intestine that ceases contracting for a brief period of time, but there is no accepted or standard definition. Paralytic ileus is a commonly observed within 3 5 d after major abdominal surgery. Passing flatus signals the resolution of the ileus. Shabsigh et al proposed the definition of ileus as the inability to tolerate solid food by postoperative day five, the need to place a nasogastric tube (NGT), or the need to stop oral intake due to abdominal distension, nausea, or emesis [13]. Usually, recovery of small bowel motility and absorption occurs within hours of surgery, whereas gastric and colonic function requires 2 5 d [5]. Barring complications, the Table 7 Recommendations for prevention and treatment of urinary extravasation and reservoir leak Urinary extravasation/reservoir leak ( %) Take your time. Use meticulous closure of conduit/pouch with seromuscular sutures. Ensure good spatulation. Always stent the ureterointestinal anastomosis. Maintain drain/catheter placement until satisfied with integrity. Make certain the pouch-draining catheter functions; if in doubt, change it under fluoroscopy. Replace the transurethral catheter under fluoroscopy or vision, leaving it for at least 1 wk in case of leakage. Divert urine with nephrostomies.

12 994 EUROPEAN UROLOGY 57 (2010) Table 8 Recommendations for prevention and treatment of infections Pneumonia (1 7.8%), sepsis ( %), and UTI (1 12.8%) Ensure early and intensive mobilisation. Use respiratory exercise aids. Encourage cessation of smoking preoperatively. Use preoperative urine culture and treatment of infection. Use intraoperative antibiotics. Ensure adequate hydration. Use incentive spirometry and mobility for atelectasis. Use supportive therapy if sepsis: oxygenation, fluid replacement, change of infected catheters and lines. Use appropriate culture, imaging, and antibiotics. UTI = urinary tract infection. Table 9 Recommendations for prevention and treatment of deep vein thrombosis and pulmonary embolus DVT ( %) and PE (0.7 6%) Use LMWH (up to 15 d after discharge). Ensure early mobilisation. Recommend intensive physiotherapy. Use epidural analgesia. Ensure early recognition with appropriate imaging and anticoagulation, if safe. DVT = deep vein thrombosis; PE = pulmonary embolism; LMWH = low-molecular-weight heparin. duration of postoperative ileus is one of the most important determinants of the length of hospitalisation [84]. Type of preoperative bowel preparation, fasting before surgery, intraoperative pain control, hypovolaemia, postoperative pain control, long-term NGT, administration of large amounts of saline, and postoperative fasting until recovery of bowel function are well-defined conditioning factors for ileus [5]. Studies examining gum chewing to hasten bowel functional recovery have been supported in a meta-analysis of colorectal surgery [85] and also one study after RC and diversion [86]. Routine NGT use is not required following RC, as the time of NGT use does not affect ileus resolution [58,60,87]. Similarly, postoperative artificial nutrition does not appear to affect the return of bowel function [88]. Some have advocated gastrostomy, but there is no evidence supporting this approach [87]. Data from gastrointestinal FT approaches support the early administration of oral fluids (day 1) and, if successful, the early restoration of oral feeding. Small bowel obstruction may be treated with NGT, intravenous fluids, and bowel rest but may require surgical correction (Table 10) Intestinal anastomotic leakage/fistulae. Whether or not a stapled anastomosis is superior to hand-sewn anastomosis has not been specifically examined in the urology literature. Only in gastrointestinal surgery have studies favoured shorter operative times using stapled rather than handsewn anastomoses, but no difference was detected in length of stay. A significant difference between stapled and handsewn ileostomy closures could not be found in the urologic literature [89]. Using an omental buttress in previously operated or irradiated intestine may also be beneficial [90] (Table 11). Fistulae may develop between the intestine and reconstructed urinary tract and from either of these to the skin or even other organs. Most commonly for urinary tract fistulae, the primary treatment is nutrition, diversion/ drainage, and treatment of any sepsis [91]. Reconstruction may be required in the longer term. A similar concept Table 10 Recommendations for prevention and treatment of paralytic ileus and small bowel obstruction Paralytic ileus ( %) and small bowel obstruction (0.3 7%) Ensure as little surgical trauma to the bowel as possible. FT protocols may be of importance. Reduce analgesic requirements. Where possible, remove the NGT with extubation (this will be dictated by the type of patient, the extent of surgery, and the bowel segment used). Begin oral fluids on day 1. Start oral feeding as soon as possible after removal of the NGT. Rest the bowel. Ensure intravenous fluids. Exclude a true obstruction requiring surgical intervention. Order TPN if no oral intake by 3 7 d. FT = fast track; NGT = nasogastric tube; TPN = total parenteral nutrition.

13 EUROPEAN UROLOGY 57 (2010) Table 11 Recommendations for prevention and treatment of intestinal leakage and fistulae Intestinal anastomotic leakage/fistulae ( %) Adhere to anastomotic principles, and take your time. Minimise surgical trauma to the bowel and mesenterium. Use meticulous hand-sewn or stapled anastomoses. Maintain adequate perioperative nutrition either orally or with parenteral support, if appropriate. Consider using the large intestine if prior to RT to the abdomen/pelvis or small bowel disease. Early recognition and reoperation with or without diversion if fistula; consider vacuum dressing. Consider TPN. RT = radiation therapy; TPN = total parenteral nutrition. applies for intestinal fistulae, but innovative devices such as vacuum dressings are gaining favour [92]. If severe sepsis occurs, percutaneous drainage of collections or open revision is essential Wound dehiscence. Interrupted closures were replaced in favour of continuous nonabsorbable sutures for closing laparotomy incisions to spread tension and reduce dehiscence [93]. However, a recent meta-analysis suggests interrupted closures with nonabsorbable sutures may significantly reduce wound dehiscence [94]. Surgeon factors are important, and attention to opposing fascia and correct tension on the suture cannot be overemphasised, although it is unclear if preemptive tension sutures assist [95]. Significant factors contributing to dehiscence include age >65 yr, wound infection, pulmonary disease, haemodynamic instability, and ostomies in the incision [96]. Treatment of dehiscence involves treatment of sepsis and early repair. Unless the defect is too large, interrupted sutures are preferred over mesh, which should be avoided if any infection is present [97]. Similar risk factors were identified for wound dehiscence as for incisional hernias (Table 12) Lymphocoele. In recent years, the extent of lymphadenectomy has increased [98,99] but with minimal morbidity [100]. Lymphocoeles remain an issue, with salvage cystectomy patients at higher risk [30,101]. Small lymphocoeles will be resorbed, while large or symptomatic lymphocoeles require percutaneous drainage, with open surgery rarely required (Table 13) Late postoperative complications Ureterointestinal and urethrointestinal anastomotic strictures. Obstruction may be benign or malignant (a second primary site or a recurrence at the ureterointestinal anastomosis). Benign strictures commonly occur during postoperative year 1 and are usually asymptomatic because they develop slowly. Early diagnosis and prompt drainage (usually with a nephrostomy) are required to prevent consequent renal parenchymal loss and infectious complications [102]. Although endoscopic and percutaneous management procedures are viable treatment options [103], open surgical revision may need to be the long-term definitive treatment, particularly if the stricture occurs after 6mo[46,104]. The type of ureteroileal anastomosis (Bricker vs Wallace) does not affect the stricture incidence [104,105]. Meticulous handling and preparation of the distal ureter are essential to minimising the risk of urine leak and postoperative stricture. The importance of ensuring good vascular supply, limiting the dissection, adequate calibre ureteroenteric anastomosis, complete excision of pathologic lesions, good drainage, and a wide spatulated and tension-free anastomosis of mucosa to mucosa remain paramount [106,107]. Tunnelling techniques for antireflux mechanisms carried a higher risk of stenosis in a randomised trial [108] (Table 14). Table 12 Recommendations for prevention and treatment of wound dehiscence Wound dehiscence (0.5 9%) Use meticulous fascial closure (1-cm bites, 1 cm along). Use extra interrupted sutures and/or tension sutures in obese, higher-risk patients. Ensure early recognition and immediate open repair if there is fascial dehiscence. Use interrupted sutures with or without treatment for sepsis. Table 13 Recommendations for prevention and treatment of lymphocoele Lymphocoele ( %) Pay attention to surgical technique. Identify and ligate (or clip) the distal and proximal lymphatic vessels during lymphadenectomy. Leave adequate peritoneal opening for drainage of lymphatic fluid. Recognise early with imaging. Use percutaneous management with or without open drainage (rare).

14 996 EUROPEAN UROLOGY 57 (2010) Table 14 Recommendations for prevention and treatment of anastomotic strictures Anastomotic strictures (7 14%) Adhere to anastomotic principles (eg, minimal ureteric dissection, watertight, well vascularised). Leak test to ensure that there are no major leaks. Leave the ureteral blood supply as intact as possible, especially minimal dissection of the left ureter. Use copious spatulation. Ensure careful placement of sutures at the apex, generally at least two interrupted sutures. Ensure early recognition and reoperation with or without diversion of urine Ureteric reflux and deterioration of renal function The importance of refluxing ureterointestinal anastomoses stems largely from UD in children with neurogenic bladder disorders. In RC patients, this issue is of minor importance, as is now increasingly being recognised. Undoubtedly, severe reflux can cause or contribute to a deterioration of renal function and therefore remains a concern with any UD. With a follow-up of 15 yr, up to 50% of patients will have upper urinary tract changes, but only 12% will demonstrate such changes at 5 yr [109]. It should be recognised that the causes for such changes are likely to be multifactorial, and in our opinion, obstruction with ureterointestinal anastomotic stenosis is more likely to contribute to a slowly progressive postoperative deterioration of renal function in RC patients. Although techniques using antirefluxing mechanisms are still used for ureterosigmoidostomy or continent reservoirs with a catheterisable abdominal stoma resulting from higher pressures, the evidence for use in orthotopic bladder substitutes is equivocal. For ileal conduits considered low-pressure diversions antirefluxing techniques for the ureteral anastomoses are not useful [110] (Table 15) Stones The incidence of upper tract stones is low at around 1% [111], but if patients are followed for a decade, rates >30% have been reported [109]. Stones can occur for three reasons: malabsorption resulting in oxalate nephropathy; reabsorption of urine solutes from the reservoir, inducing an acidosis; and chronic infections with urease-producing bacteria [111]. Prevention can be aided by preserving the most distal cm of ileum and postoperatively by encouraging frequent voiding with minimal residual volumes. Treatment of bacteriuria until the urine is sterile is controversial [111,112], because about 40% of patients with an orthotopic bladder will have persistent bacteriuria and may have other adverse affects, such as resistant organisms. Pouch stones are related to poor emptying and foreign bodies in the reservoir or (rarely) in a conduit. Exposed metallic staple lines and mesh are at a higher risk of stone formation and should be avoided [113] (Table 16) Chronic/recurrent pyelonephritis A positive urine culture is a common finding in patients with UD, but this does not translate to symptomatic infection [112]. However, symptomatic UTI (including pyelonephritis) may develop in almost a quarter of patients [109]. Symptomatic UTIs must be treated expeditiously with appropriate antibiotics and in cases of sepsis supportive therapy [114]. Pouchitis is a soft tissue infection occurring almost exclusively in the first few months but rarely in a mature pouch, but few data are available. Table 15 Recommendations for prevention and treatment of ureteric reflux and deterioration of renal function Ureteric reflux (1 12%) and deterioration of renal function (0.3 27%) Do not use antireflux techniques with ureteroileal anastomoses, only with colon. Treat reflux only if it is associated with clinical problems (recurrent infections). Monitor serum creatinine every 3 6 mo for the first 2 yr, and then annually. Monitor upper urinary tracts at 3 4 mo, and then annually. Consider the age and life expectancy of the patient. Recommend ureteric reimplantation with consideration for reflux protection. Table 16 Recommendations for prevention and treatment of stones Stones (3.9 9%) Ensure adequate reservoir size. Ensure adequate emptying of the reservoir (angulation of conduit; ISC in orthotopic bladder substitutes with residual, frequent checking of adequate pouch evacuation). Minimise UTI and bacteriuria. Ensure hydration. Ensure early recognition of obstructions. Use ISC, if required; use a minimally invasive technique to treat calculi. ISC = intermittent self-catheterisation; UTI = urinary tract infection.

15 EUROPEAN UROLOGY 57 (2010) Table 17 Recommendations for prevention and treatment of pyelonephritis Recommendation for prevention Treatment recommendation Chronic/recurrent pyelonephritis ( %) Recurrent symptomatic UTI not related to ureteral obstruction or reflux requires fluoroscopy of the reservoir or conduit to determine whether there is poor emptying of the reservoir and to identify stenotic areas [115]. In orthotopic bladder substitutes, stagnant urine with incomplete emptying because of stricture at the urethral anastomosis or voiding dysfunction should be considered. In summary, the presence of small bowel intestine appears to promote asymptomatic bacterial colonisation, but urosepsis rarely occurs unless the patient has recurrent symptomatic UTI. Prophylactic antibiotics are recommended only for patients with recurring symptomatic UTI, but treating a positive urinary culture in the absence of specific voiding symptoms is not advocated in this patient population [116] (Table 17) Metabolic disorders Metabolic consequences relate to reabsorption and vitamin deficiencies [117]. Patients with preexisting renal disease are less able to compensate for metabolic changes resulting from UD [43]. For ileum and colon, the most common metabolic disturbance is hyperchloraemic metabolic acidosis. Rare occurrences of total body potassium depletion and other effects, such as hypocalcaemia, hypomagnesaemia, and hyperamonaemia, are possible. The presenting symptoms are fatigue, anorexia, and diarrhoea. Treatment in the short term involves intravenous hydration and monitoring of electrolytes plus bicarbonate. Metabolic imbalances usually respond promptly to an adaptation of the substitution therapy [23,38]. Malabsorptive vitamin B 12 deficiency may be a concern and a relatively common problem [39]. Distal terminal ileum preservation is essential, and it may take 3 4 yr to deplete vitamin B 12 stores. Parenteral or oral replacement should be initiated prior to symptoms [43,46] (Table 18) Miscellaneous Check regularly to exclude obstruction. Exclude stagnation of urine in the conduit and residual urine in orthotopic bladder substitutes. Ensure adequate and constant diuresis. Employ early culture and treatment, if symptomatic. Avoid overtreating and cultivating resistant organisms Orthotopic bladder substitute retention and rupture A variable number of patients will have problems with incomplete orthotopic bladder substitute emptying, although the incidence of this functional problem is not known. It may be severe and rarely leads to reservoir rupture with minor trauma [118]. What defines retention is contentious but probably between 100 ml and 200 ml Table 18 Recommendations for prevention and treatment of metabolic disorders Recommendation for prevention Treatment recommendation Metabolic disorders (0 3%) Preserve the distal ileum. Monitor vitamin B 12, ph bicarbonate, and electrolytes. Use generous replacement of vitamin B 12, if required. Ensure adequate positioning of conduits for rapid emptying. Ensure adequate emptying of the pouch, conduits, and the orthotopic bladder substitute. Check adequate emptying. Start oral bicarbonate early. Use early correction as appropriate. Ensure adequate management of orthotopic bladder substitution. depending on the type and size of the reservoir. Chronic retention in orthotopic bladder substitutes may be related to the initial capacity and configuration of the orthotopic bladder substitute pouch at the time of surgery. Education and the patient s ability to void the bladder regularly, excessive mucous formation, decompensation of the orthotopic bladder substitute, and angulation just proximal to the urethral anastomosis are important. Successful conservative management may require attempts to reduce mucous accumulation (eg, N-acetyl-L-cysteine), prevention of infection, and/or intermittent self-catheterisation. Orthotopic bladder substitute rupture is rare and may not always require surgical repair [119,120]. Whether surgical technique of orthotopic bladder substitute formation plays a role in facilitating rupture is unknown; in women, the use of a supportive hammock has been advocated to prevent this complication [121] (Table 19) Stomal hernia and stenosis Herniasmayoccurinthewoundoradjacenttostomasand may require revision, often without disrupting the whole conduit or reservoir. Mesh may be used to reinforce weakened fascial planes around stomas [122]. However, relocation of the stoma to the contralateral side is an important consideration because of the high rate of recurrence without stoma relocation. Stomal stenosis, Table 19 Recommendations for prevention and treatment of orthotopic bladder substitute retention and rupture Recommendation for prevention Treatment recommendation Orthotopic bladder substitute retention (>1.5%) and rupture (rare) ISC = intermittent self-catheterisation. Encourage patient education with a stomal therapist. Ensure adequate emptying. Reduce mucus. Use ISC in patients with high residual urine. Use ISC or cystoscopic drainage. Use a transurethral catheter. Reduce mucous formation. Consider open surgical repair.