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Risk factors and reasons for reoperation after radical cystectomy
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Urologic Oncology: Seminars and Original Investigations 000 (2019) 1−9
Risk factors and reasons for reoperation after radical cystectomy Stephen W. Reese, M.D.a,*, Emily Ji, B.A.a, Marco Paciotti, M.D.e, Jeffrey Leow, M.B.B.S.a, David A. Mahvi, M.D.b, Graeme Steele, M.D.a, Richard D. Urman, M.D.c,d, Edward E. Whang, M.D.b,d, Adam S. Kibel, M.D.a, Matthew Mossanen, M.D.a a
Division of Urological Surgery, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA Department of General Surgery, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA c Department of Anesthesiology, Perioperative and Pain Medicine, Brigham and Women’s Hospital, Boston, MA d Center for Perioperative Research, Brigham and Women’s Hospital, Boston, MA e Department of Urology, Humanitas Clinical and Research Center IRCCS, Rozzano, Italy b
Received 2 July 2019; received in revised form 25 September 2019; accepted 22 October 2019
Abstract Purpose: Reoperation after radical cystectomy (RC) is common but the types of reoperation after RC and associated risk factors have not been fully characterized. Here, we provide a detailed, contemporary account of the factors that drive surgical reoperation within the first 30-days after surgery, identify at risk patient populations, and describe common reoperations. Materials and methods: The American College of Surgeons National Surgical Quality Improvement Program database (2012−2017) was analyzed to identify 30-day reoperation rates after RC. Captured variables included demographic, preoperative, operative, and postoperative characteristics. Postoperative characteristics included complications, including types of reoperation, length of stay, unplanned readmissions, and discharge destination. Pearson chi-squared and multivariable logistic regression models were used for analysis. Results: A total of 10,848 patients underwent RC and there were 633 (5.84%) unplanned reoperations. On multivariable logistic regression, patient factors associated with increased risk of reoperation included longer operative times at index procedure (>90th percentile operative time) (OR1.41 [1.08−1.83], P = 0.02), smoking (OR1.34 [1.11−1.63], P < 0.01), obesity (BMI≥30) (OR 1.29 [1.04−1.60], P = 0.02) and chronic obstructive pulmonary disease (OR1.74 [1.36−2.3], P < 0.01). Other significant factors included clinically significant hypertension, perioperative blood transfusion, and male sex. The most common reoperation procedures were those performed on the gastrointestinal tract, accounting for 60.59% (349) of all reoperations, followed by skin/subcutaneous procedures 14.76% (85), followed by Genitourinary procedures at 8.16% (47). Patients who underwent reoperation were at higher risk for readmission, discharge to a facility, and death (P < 0.01). Conclusion: Reoperation after RC is associated with approximately 5% rate of reoperation within 30 days of surgery. The most common reason for reoperation was related to the gastrointestinal tract, accounting for more than 60% of all reoperations. Risk factors for reoperation included longer surgical times, smoking, obesity, chronic obstructive pulmonary disease, perioperative blood transfusion, and clinically significant hypertension. Knowledge of these factors can aid in operative planning and counseling and lead to possible strategies to reduce reoperations in the early perioperative setting. Ó 2019 Elsevier Inc. All rights reserved.
1. Introduction Bladder cancer is the sixth most common cancer in the United States with an estimated 80,470 new cases and 17,670 deaths in 2019 [1]. Radical cystectomy (RC) along with neoadjuvant chemotherapy is the standard of care for patients with muscle invasive and recurrent high-risk *Corresponding author. Tel.: 617-525-7372; Fax: (617) 525-9894. E-mail address: [email protected] (S.W. Reese). https://doi.org/10.1016/j.urolonc.2019.10.011 1078-1439/Ó 2019 Elsevier Inc. All rights reserved.
noninvasive bladder cancer [2] and is considered one of the most complex and morbid urologic procedures [3−6]. Despite new enhanced recovery after surgery (ERAS) protocols, complication rates remain around 50% and 90-day readmission rates are 30% which is similar to the preERAS era [3,7]. While the literature on postoperative complications after RC is well documented, there is a relative paucity of data on the management of these complications. Reoperation rates have been described at around 5% during the
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postoperative period, however, more detailed investigations into the etiology and risk factors of reoperation after RC have been limited to single-institution studies [8−10]. Understanding the factors that increase the risk of reoperation as well as the types of reoperation is valuable for preoperative planning, patient counseling, and quality improvement. Here, we present a detailed analysis of reoperation after RC using data from the American College of Surgeons-National Surgical Quality Improvement Program (ACS-NSQIP), a large, validated, national dataset. Our study aims to examine the nature of reoperations patients undergo following RC, along with the surgical and patient risk-factors associated with higher reoperation rates. 2. Methods 2.1. Data source and patient selection The current study utilized the ACS-NSQIP database, a large national database that captures risk-adjusted surgical patient data on demographics, medical comorbidities, operative, and postoperative outcome measures [11]. Approximately 400 hospitals participate in ACS-NSQIP and include teaching and nonteaching hospitals, urban and rural alike [12]. A query of the ACS-NSQIP database identified 10, 848 patients undergoing RC from the years 2012 to 2017. We specifically focused on this time period as this was the first-time unplanned reoperations, including the associated reoperation procedures, were included in the dataset. Patients were identified as having undergone a RC using Current Procedural Terminology (CPT) codes 51590, 51595, 51596, 51590, 51595, 51596, 51575, 51570. CPT codes were selected based on prior studies using CPT codes to identify RC patients [13,14]. Patients older than 18 years of age were included in the study. Patients who underwent reoperation for reasons other than for a diagnosis of bladder cancer (ICD-9, 188.x) were excluded from the study. 2.2. Variables and outcomes For each patient, captured variables included demographic, preoperative, operative and postoperative characteristics. Demographic variables included age, sex, body mass index (BMI), American Society of Anesthesiologists physical status (PS), and specific associated medical comorbidities. Preoperative functional status was measured based on a patient’s ability to perform activities of daily living in the 30 days before the procedure, as assessed by a nurse trained to review clinical data specifically for the NSQIP program. The use of chronic steroids was defined as steroid use within the 30 days before and up until the principal operative procedure. Smoking was defined as current smoking within the past year. The principal surgical procedure was RC, with or without a continent diversion. Preoperative laboratory values included creatinine and albumin. Postoperative surgical complications included wound infections,
dehiscence, and bleeding requiring transfusion. Transfusion was defined as at least 1 unit of packed or whole red blood cells starting at the time of surgery up until 72 hours postoperatively. Postoperative medical complications included pneumonia, pulmonary embolism, deep venous thromboembolism, unplanned intubations, acute kidney injury, urinary tract infection, myocardial infarction, stroke, sepsis, and death. We also examined those patients whose hospital length of stay was greater than 30 days, who experienced an unplanned readmission, and patient discharge destinations. The primary outcome was unplanned reoperation within 30 days of the index procedure. NSQIP defines unplanned reoperation as “unplanned return to the operating room for a surgical procedure related to either the index or concurrent procedure performed and may occur at any hospital or surgical facility.” Secondary outcomes included postoperative complications other than reoperation. Reoperations were reported as CPT codes. In order to provide clinically relevant information from the NSQIP CPT-level data, we utilized the Clinical Classification Software procedure categories formulated by the Healthcare Cost and Utilization Project [15]. The Clinical Classification Software procedure categories provide a standardized means of converting CPT or ICD level data into higher-level categorization structures. We further categorized reoperations based on organ system to provide clinically meaningful and interpretable data. 2.3. Statistical analysis Summary statistics of categorical variables were evaluated using Pearson chi-squared test. Multivariable logistic regression analysis was then performed in a stepwise fashion based on univariate analysis to determine associations between patient characteristics and unplanned reoperation. Included in the model, were age, gender, BMI, diabetes, hypertension requiring medication, history of chronic obstructive pulmonary disease (COPD), smoking, steroid use, weight-loss, type of diversion (continent vs. incontinent), American Society of Anesthesiologists physical status, perioperative transfusion, and operative time. All statistical analyses were performed using SAS Studio University Edition (SAS, Charlotte, NC) and a 2-sided significance level was set at P < 0.05. This study was reviewed by the Brigham and Women’s Hospital Institutional Review Board (Boston, MA) and found to be exempt given the deidentified nature of the data. 3. Results 3.1. Patient characteristics and risk factors for reoperation Descriptive characteristics of 10,848 patients who underwent RC with either an ileal conduit or continent diversion are presented in Table 1, stratified based on whether the
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Table 1 Patient characteristics for radical cystectomy, 2012 to 2017. Demographics
Total (n = 10,848)*
No reoperation (n = 10,215)
Reoperation (n = 633)
69 (10.52)
69 (10.5‘4)
69 (10.10)
Age (y) Sex Female Male BMI (kg/m2) <18.5 18.5−24.9 24.9−30 ≥30 Comorbidities Diabetes mellitus Noninsulin (%) Insulin dependent (%) Hypertension Yes COPD Yes Smoker Yes Functional status (%)* Partially dependent Totally dependent Steroid use Yes Weight loss >10% Yes Dyspnea (%) Yes Procedural characteristics Reconstruction Ileal conduit Neobladder ASA class* ASA 2 ASA 3 ASA 4 Mean operative time <50th per. (329 min) 50th−75th per. (330−418 min) 75th−90th per. (419−509 min) >90th per. (510min) Preoperative laboratories Creatinine* Cr ≤1 Cr 1.01 <-> 1.5 Cr > 1.5 Albumin* Alb < 3 Alb 3 <-> 3.99 Alb ≥4 Intra-op blood transfusion Yes
P value
P = 0.66 P = 0.02** 2,559 (23.59) 8,289 (76.41)
2,434 (23.83) 7,781 (76.17)
125 (19.75) 508 (80.25)
248 (2.29) 2,809 (25.89) 4,114 (37.92) 3,677 (33.90)
226 (2.21) 2,652 (25.96) 3,924 (38.41) 3,413 (33.41)
22 (3.48) 157 (24.80) 190 (30.02) 264 (41.71)
1,399 (12.90) 735 (6.78)
1,326 (12.98) 687 (6.73)
73 (11.53) 48 (7.58)
6,482 (59.75)
6,059 (59.31)
423 (66.82)
841 (7.75)
754 (7.38)
87 (13.74)
2,538 (23.40)
2,357 (23.07)
181 (28.59)
180 (1.66) 58 (0.54)
163 (1.60) 52 (0.51)
17 (2.69) 6 (0.95)
401 (3.70)
373 (3.65)
28 (4.42)
318 (2.93)
298 (2.92)
20 (3.16)
898 (8.28)
814 (7.97)
84 (13.27)
9,228 (85.07) 1,620 (14.93)
8,694 (85.11) 1,521 (14.89)
534 (84.36) 99 (15.64)
2,499 (23.16) 7,603 (70.47) 687 (6.37)
2,364 (23.37) 7,172 (70.60) 622 (6.12)
135 (21.39) 431 (68.30) 65 (10.30)
5,496 (50.85) 2,699 (24.88) 1,557 (14.35) 1,096 (10.10)
5,194 (50.85) 2,544 (24.90) 1,466 (14.35) 1,011 (9.90)
302 (47.71) 155 (24.49) 91 (14.38) 85 (13.43)
4,846 (45.91) 4,117 (39.00) 1,593 (15.09)
4,579 (46.07) 3,874 (38.98) 1,486 (14.95)
267 (43.27) 243 (39.38) 107 (17.34)
391 (5.48) 3,061 (42.90) 3,683 (51.62)
361 (5.36) 2,867 (42.61) 3,501 (52.03)
30 (7.39) 194 (47.78) 182 (44.83)
4,100 (37.79)
3,828 (37.47)
272 (42.97)
P < 0.01**
P = 0.44
P < 0.01** P < 0.01** P < 0.01** P = 0.04**
P = 0.32 P = 0.73 P < 0.01**
P = 0.61
P = <0.01**
P = 0.04**
P = 0.20
P = 0.01**
P < 0.01**
* Missing data: Functional Status (31) j ASA (59) j Cr (292) j Albumin (3,713).
patient experienced an unplanned reoperation within 30days of the index operation. The median patient age was noted to be 69 years of age and approximately 76% of patients were male. Overall, 633 (5.84%) of patients
underwent at least 1 unplanned reoperation within 30 days of their index operation. Of those patients who underwent reoperation, 97 (15.32%) underwent at least 1 additional reoperation. On univariate analysis, smoking was
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Table 2 Multivariable analysis of risk factors for reoperation
Age Sex Female Male BMI 18.5−24.9 <18.5 25−30 ≥30 Diabetes No DM1 DM2 Hypertension No Yes COPD No Yes Smoking No Yes Steroid No Yes Weight loss No Yes Neobladder No Yes ASA class ASA 2 ASA 3 ASA 4 Peri-op transfusion No Yes Mean operative time <50th per. 50th−75th per. 75th−90th per. >90th per.
approximately 85% of patients undergoing reconstruction with ileal conduit. On multivariable analysis, we found a number of independent variables to be associated with reoperation. Male sex (OR: 1.36, CI: 1.10−1.67, P = <0.01), smoking (OR: 1.34, CI: 1.11−1.63, P < 0.01), history of COPD (OR: 1.74, CI:1.36−2.23, P < 0.01), perioperative blood transfusion (OR: 1.25 CI: 1.06−1.48, P = 0.01), hypertension requiring medication (OR: 1.34, CI: 1.11−1.62, P <0.01), obesity (BMI≥30) (OR 1.29 (1.04−1.60), P = 0.02 and operative times greater than 90th percentile (OR: 1.41, CI:1.08−1.83, P = 0.02).
OR (95% CI)
P value
1.01 (0.99−1.01)
0.35
1 (ref) 1.36 (1.10−1.67)
− <0.01**
1 (ref) 1.58 (0.97−2.56) 0.81 (0.65−1.01) 1.29 (1.04−1.60)
− 0.07 0.06 0.02**
1 (ref) 0.91 (0.66−1.25) 0.79 (0.61−1.02)
− 0.90 0.18
1 (ref) 1.34 (1.11−1.62)
− <0.01**
1 (ref) 1.74 (1.36−2.23)
− <0.01**
1 (ref) 1.34 (1.11−1.63)
− <0.01**
1 (ref) 1.15 (0.77−1.72)
− 0.48
1 (ref) 0.95 (0.59−1.52)
− 0.82
1 (ref) 1.09 (0.87−1.38)
− 0.46
1 (ref) 0.91 (0.74−1.12) 1.40 (0.99−1.90)
− 0.65 0.07
Approximately 5.84% or 633 patients underwent at least 1 reoperation within 30 days of their index procedure. The median time to reoperation depended on the type of procedure being performed. Vascular/cardiac reoperations occurred closest to the index operation at a median of 6 days, while thoracic/airway procedures occurred furthest in time from the index operation at a median of 21 days (Tables 3A and 3B). Some patients underwent at least 2 or more reoperations, 97 (15.32%) with 68 patients undergoing 2 unplanned reoperations (10.74%) and 29 patients (4.58%) undergoing 3 unplanned reoperations within the 30 days after the index procedure. The most common reoperation procedures were those performed on the Gastrointestinal tract, accounting for 60.59% (349) of all reoperations, followed by skin/subcutaneous procedures 14.76% (85), followed by GU procedures at 8.16% (47), followed by vascular/cardiac procedures 7.12% (41). See Figure 1 and Table 3B for full detail of reoperations.
1 (ref) 1.25 (1.06−1.48)
− 0.01**
3.3. Postoperative complications
1 (ref) 1.04 (0.85−1.28) 1.06 (0.83−1.36) 1.41 (1.08−1.83)
− 0.36 0.58 0.02**
** Signifies significance <0.05.
associated with a significantly higher rate of reoperation compared to nonsmokers (28.59 vs. 23.07%, P = <0.01), along with patients with a diagnosis of COPD (13.74 vs. 7.38%, P < 0.01). Patients with a BMI ≥30 were noted to have higher rates of reoperation (41.71 vs. 33.41%, P < 0.01). Patients who had a longer index operation time, especially those >90th percentile (>510 minutes) (Table 1, P = 0.04) were also noted to have significantly higher rates of reoperation. Other significant findings included functional status, hypertension requiring antihypertensive medication, dyspnea, and male sex (Table 1, P < 0.05). The type of reconstruction did not affect rates of reoperation (Table 1, P = 0.61), with
3.2. Reoperation procedures
In terms of surgical and medical postoperative complications, undergoing an unplanned reoperation was associated with an increased risk of both categories of complications in the postoperative period (Table 4). Patients who underwent reoperation were more likely to have an infectious complication, including superficial infection (10.90 vs. 5.34%, P < 0.01), deep wound infection (9.48 vs. 0.96%, P < 0.01), organ space infection (30.02 vs. 5.66%, P < 0.01) and wound dehiscence (32.86 vs. 0.79%, P < 0.01). Patients with an unplanned reoperation were also more
Table 3A Reoperation characteristics, Freq (%) Reoperation Number of reoperations within 30 days One Two Three
633 (5.84%) 536 (84.68) 68 (10.74) 29 (4.58)
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Freq. (%)
Median days to procedure
Gastrointestinal* Skin/subcutaneous Genitourinary Vascular/cardiac Hernia repair Thoracic/airway Orthopedic CNS Other
349 (60.59%) 85 (14.76%) 47 (8.16%) 41 (7.12%) 27 (4.69%) 12 (2.08%) 8 (1.39%) 2 (0.35 %) 5 (0.89%)
11 12 16 6 11 21 16 8 13
* Includes endoscopy.
likely to die (6.64 vs. 1.59%, P < 0.01), have length of hospital stay >30 days (15.80 vs. 1.06%, P < 0.01), have an unplanned readmission (37.60 vs. 19.88%, P <0.01), and be discharged to a destination that was not their home (38.86 vs. 13.69%, P < 0.01).
4. Discussion In our study, we found that more than 1 in 20 patients (5.84% of the study cohort) underwent at least 1 unplanned reoperation within 30-days of RC for management of bladder cancer and some patients underwent multiple reoperations within this 30-day period. We identified a number of surgical and medical characteristics associated with an increased likelihood of reoperation, including longer operative times and perioperative blood transfusion, along with recent history of smoking, COPD, clinically significant
Fig. 1. Reoperation after cystectomy.
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hypertension, and obesity. While there is limited reporting of the exact timing of reoperation in the literature [16], we found the median time to reoperation, ranged between 6 and 21 days depending on the category of reoperation. Across all reoperations, procedures on the gastrointestinal tract were the most common operation, accounting for 60.59% of all reoperations within the first 30 days after surgery. The strength of our study lies in its ability to provide a detailed account of the reoperations and complications patients develop after RC using a contemporary dataset from a validated, large national cohort. Our estimate of unplanned reoperation rates after RC is consistent with prior estimates of reoperation in the literature at approximately 5% [8−10,17,18]. A recent study examining complications after RC found that fascial dehiscence, bowel obstruction, and enteric anastomotic leak were the most common reasons for reoperation in the earlier perioperative period [19]. Our study echoes a similar finding in that almost 80% of the reoperations in our study were either gastrointestinal or wound related. With respect to operative characteristics, we found that prolonged operative time and perioperative blood transfusion were associated with increased likelihood of reoperation. One possible explanation for the association between increasing operative length and reoperation is that longer operative times reflect procedural complexity and/or surgeon skill thus predisposing to higher rates of reoperation [20]. However, longer operative times may also be an independent risk factor for perioperative complications, having been demonstrated in the surgical literature to be associated with increased risk of infection, sepsis/shock, prolonged intubation, deep venous thrombosis, impaired wound healing and mortality [21−26]. Prolonged operative times may predispose patients to deleterious side effects of anesthesia, including escalating anesthetic doses, hypothermia, electrolyte derangement, and increased physiologic stress. One potential strategy to minimize operative times is by having these surgeries performed at high-volume centers or with high-volume surgeons which has been associated with decreased rates of perioperative complications [27,28]. The association between perioperative blood transfusion and increased rates of reoperation is likely multifactorial. The need for blood transfusion may suggest clinically significant blood loss and/or postoperative bleeding necessitating return to the operating room. In addition, a well described side effect of blood transfusion is immunosuppression, which exhibits a dose-dependent response to increasing units of blood transfused [29,30]. Downstream consequences of this effect may include increased rates of infection and/or compromised wound healing leading to higher rates of reoperation [31,32]. Indeed, the association between blood transfusion and infectious complication has been described in patients undergoing RC [33−35]. The judicious use of perioperative blood products may lead to
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Table 4 Postoperative complications after radical cystectomy, 2012 to 2017 Complication
Surgical complications Superficial infection Deep wound infection Organ space infection Bleeding Dehiscence Medical complications Pneumonia Pulmonary embolism Unplanned intubation Failure to wean from vent AKI Renal failure UTI CVA Cardiac arrest Myocardial infarction DVT Sepsis Septic shock Death Hosp > 30 days Readmission Discharge destination Home Other
Total (n = 10,848)
No reoperation (n = 10,215)
Reoperation (n = 633)
P value
614 (5.66) 158 (1.46) 768 (7.08) 4,100 (37.79) 289 (2.66)
545 (5.34) 98 (0.96) 578 (5.66) 3,828 (37.47) 81 (0.79)
69 (10.90) 60 (9.48) 190 (30.02) 272 (42.97) 208 (32.86)
<0.01 <0.01 <0.01 <0.01 <0.01
310 (2.86) 194 (1.79) 287 (2.65) 199 (1.83) 148 (1.36) 214 (1.97) 922 (8.50) 60 (0.55) 116 (1.07) 178 (1.64) 299 (2.76) 955 (8.80) 310 (2.86) 204 (1.88) 208 (1.92) 2,269 (20.92)
247 (2.42) 174 (1.70) 202 (1.98) 112 (1.10) 105 (1.03) 185 (1.81) 851 (8.33) 51 (0.50) 95 (0.93) 151 (1.48) 259 (2.54) 802 (7.85) 198 (1.94) 162 (1.59) 108 (1.06) 2,031 (19.88)
63 (9.95) 20 (3.16) 85 (13.43) 87 (13.74) 43 (6.79) 29 (4.58) 71 (11.22) 9 (1.42) 21 (3.32) 27 (4.27) 40 (6.32) 153 (24.17) 112 (17.69) 42 (6.64) 100 (15.80) 238 (37.60)
<0.01 <0.01 <0.01 <0.01 <0.01 <0.01 0.01 <0.01 <0.01 <0.01 <0.01 <0.01 <0.01 <0.01 <0.01 <0.01 <0.01
9,204 (84.85) 1,644 (15.15)
8,817 (86.31) 1,398 (13.69)
387 (1.14) 246 (38.86)
improved surgical outcomes and also minimize the risk of perioperative reoperation [29]. A number of patient characteristics were associated with increased rates of reoperation. Specifically, patients with a history of smoking, COPD, and hypertension requiring medication and obesity (BMI ≥ 30) were associated with higher rates of reoperation. Smoking, COPD, and hypertension likely reflect vasculopathy and decreased ability for optimal tissue oxygenation leading to poor wound healing. Indeed, the association between smoking, infection, poor wound healing, and suppressed immune system is well documented in the surgical literature [36]. Smoking, compromised vascularity, and immunosuppression likely leads to an increased risk of reoperation given increased risk of wound dehiscence, cardiopulmonary-related events, thrombotic events, and infection [37−39]. Smoking-cessation and improvement in cardiopulmonary reserve prior to surgery may represent potentially modifiable risk factors for decreasing rates of reoperation and surgical complications in the perioperative period [37,40,41]. In our study, obese individuals (BMI ≥ 30) were found to have an increased risk of reoperation compared to normal weight individuals. The association between obese individuals and increased rates of surgical complication, including high-grade complications like reoperation has been previously demonstrated in the literature [19,42,43]. Obesity
may increase reoperation rates given obesity likely increases the mechanical tension across the surgical wound, leading to an increased risk of wound dehiscence [16,44]. Obesity and associated metabolic syndrome may lead to compromised wound healing, predisposing to such complications like fascial dehiscence, anastomotic leak, or may impair immunity, leading to increased susceptibility to infectious complications [45]. Indeed, obesity has been associated with an increased risk of infectious complications after RC, likely in some cases necessitating surgical intervention [33,46,47]. Optimizing preoperative weight and nutritional status as well as targeting at-risk populations may serve as an important and implementable way to reduce perioperative reoperation and complication. Patients who underwent a reoperation within 30 days were more likely to experience postoperative medical and surgical complications compared to those patients who did not (Table 4). While we were unable to link causality, a priori reasoning would suggest that in some cases, like wound dehiscence, this may have been an indication for surgery, while in others, like postoperative pneumonia, this may have resulted from undergoing reoperation. Despite being unable to ascertain causality, we found the burden of reoperation and associated complications is considerable and highlighted by the higher rates of death, unplanned readmission, prolonged length of hospital stay, and discharge to
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facility other than home. Unplanned readmissions after RC is associated with increased patient mortality after RC and increased rates of postoperative complications [48−50]. Identification of patients who are at risk for reoperation and targeted interventions to reduce reoperation may be an important way of reducing postoperative readmission and mortality. Our study highlights risk factors associated with unplanned reoperation after RC. Along a spectrum, important drivers of reoperation after RC include both modifiable and nonmodifiable risk-factors. For modifiable risk factors, preoperative interventions that can address a patient’s obesity or aid in smoking cessation and/or cardiopulmonary reserve may have the potential to reduce the rates of reoperation in patients undergoing RC and the subsequent sequelae of unplanned hospital readmission, prolonged hospital stays, and nonhome discharges. For nonmodifiable risk factors, increased adoption of preoperative risk assessment would be beneficial. Identifying high-risk patients who are more likely to undergo reoperation or fare-worse after surgery would benefit from preoperative planning that would anticipate and direct intraoperative and postoperative resources to aid and risk-mitigate this population. Such interventions could include preoperative physical rehabilitation, enhanced and tailored antibiosis for patients at risk for postoperative infections, and directing anticipatory resources to patients in need in the postoperative setting. Such preoperative risk assessment tools could also be helpful in identifying which patients would benefit from ERAS protocols and identifying those patients who would not benefit, instead of applying a “one size fits all” approach to postoperative recovery. Several limitations of the study warrant further discussion. First, our study was performed in a retrospective manner and along with the deficiencies associated with a retrospective study design, we were not able to capture important variables of interest. For example, we were not able to distinguish if patients had received neoadjuvant chemotherapy as this variable is no longer collected in NSQIP. Conceivably, patients who received neoadjuvant chemotherapy could be at higher risk for postoperative complications and thus also at risk for reoperation. Yet, studies have not shown significantly higher postoperative complication rates for patients receiving neoadjuvant chemotherapy compared to patients who had upfront RC, however these studies do not focus on reoperation specifically [51,52]. Next, we were unable to distinguish between a minimally invasive vs. open approach as there currently do not exist CPT codes to capture this distinction. Robotic cystectomies have been postulated to take longer time and may be associated with a higher learning curve. Our analysis was limited to the 30-days postprocedurally, thus limiting the scope of the study to immediate postoperative outcomes. However, reoperations have been reported beyond the 30-day period, thus our study likely underestimates the true incidence of reoperations and may not capture the types of reoperations
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that occur in a delayed fashion [10]. In addition, smaller, nonoperative procedures such as need for bedside incision and drainage or interventional radiology procedures are not captured but would represent an invasive intervention nonetheless. The specific reason for reoperation must be extrapolated from diagnosis codes leaving a degree of imprecision. Surgical volume, pack years of smoking, history of prior abdominal surgery, and clinicopathologic data such as tumor stage, grade, and histologic subtype were not documented in the database and thus could not be accounted for. Similarly, we could not control for hospital level data such as hospital volume, geographic location, or other sociodemographic data that may have influenced the outcome. 5. Conclusion In conclusion, we found the overall reoperation rate to be 5.84% within the first 30 days of RC and risk factors for reoperation included long operative times, male sex, perioperative blood transfusion, smoking, obesity, COPD, and clinically significant hypertension. An understanding of the relationship between patients who undergo RC and the kind of reoperations patients are most likely to experience is important in preoperative counseling, operative planning, and risk-stratification. This knowledge is imperative in directing efforts to reduce reoperation, mitigate postoperative complication, and improve patient outcomes. Supplementary materials Supplementary material associated with this article can be found in the online version at https://doi.org/10.1016/j. urolonc.2019.10.011. References [1] Siegel RL, Miller KD, Jemal A. Cancer statistics, 2019. CA Cancer J Clin 2019;69:7–34. https://doi.org/10.3322/caac.21551. [2] Stein JP, Lieskovsky G, Cote R, Groshen S, Feng AC, Boyd S, et al. Radical cystectomy in the treatment of invasive bladder cancer: longterm results in 1,054 patients. J Clin Oncol 2001;19:666–75. https:// doi.org/10.1200/JCO.2001.19.3.666. [3] Djaladat H, Katebian B, Bazargani ST, Miranda G, Cai J, Schuckman AK, et al. 90-Day complication rate in patients undergoing radical cystectomy with enhanced recovery protocol: a prospective cohort study. World J Urol 2017;35:907–11. https://doi.org/10.1007/s00345-0161950-z. [4] Daneshmand S, Ahmadi H, Schuckman AK, Mitra AP, Cai J, Miranda G, et al. Enhanced recovery protocol after radical cystectomy for bladder cancer. J Urol 2014;192:50–6. https://doi.org/ 10.1016/j.juro.2014.01.097. [5] Hautmann RE, de Petriconi RC, Volkmer BG. 25 years of experience with 1,000 neobladders: long-term complications. J Urol 2011;185:2207–12. https://doi.org/10.1016/j.juro.2011.02.006. [6] Mossanen M, Gore JL. The burden of bladder cancer care. Curr Opin Urol 2014;24:487–91. https://doi.org/10.1097/MOU. 0000000000000078. [7] Semerjian A, Milbar N, Kates M, Gorin MA, Patel HD, Chalfin HJ, et al. Hospital charges and length of stay following radical
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Risk factors and reasons for reoperation after radical cystectomy Stephen W. Reese, M.D.a,*, Emily Ji, B.A.a, Marco Paciotti, M.D.e, Jeffrey Leow, M.B.B.S.a, David A. Mahvi, M.D.b, Graeme Steele, M.D.a, Richard D. Urman, M.D.c,d, Edward E. Whang, M.D.b,d, Adam S. Kibel, M.D.a, Matthew Mossanen, M.D.a a
Division of Urological Surgery, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA Department of General Surgery, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA c Department of Anesthesiology, Perioperative and Pain Medicine, Brigham and Women’s Hospital, Boston, MA d Center for Perioperative Research, Brigham and Women’s Hospital, Boston, MA e Department of Urology, Humanitas Clinical and Research Center IRCCS, Rozzano, Italy b
Received 2 July 2019; received in revised form 25 September 2019; accepted 22 October 2019
Abstract Purpose: Reoperation after radical cystectomy (RC) is common but the types of reoperation after RC and associated risk factors have not been fully characterized. Here, we provide a detailed, contemporary account of the factors that drive surgical reoperation within the first 30-days after surgery, identify at risk patient populations, and describe common reoperations. Materials and methods: The American College of Surgeons National Surgical Quality Improvement Program database (2012−2017) was analyzed to identify 30-day reoperation rates after RC. Captured variables included demographic, preoperative, operative, and postoperative characteristics. Postoperative characteristics included complications, including types of reoperation, length of stay, unplanned readmissions, and discharge destination. Pearson chi-squared and multivariable logistic regression models were used for analysis. Results: A total of 10,848 patients underwent RC and there were 633 (5.84%) unplanned reoperations. On multivariable logistic regression, patient factors associated with increased risk of reoperation included longer operative times at index procedure (>90th percentile operative time) (OR1.41 [1.08−1.83], P = 0.02), smoking (OR1.34 [1.11−1.63], P < 0.01), obesity (BMI≥30) (OR 1.29 [1.04−1.60], P = 0.02) and chronic obstructive pulmonary disease (OR1.74 [1.36−2.3], P < 0.01). Other significant factors included clinically significant hypertension, perioperative blood transfusion, and male sex. The most common reoperation procedures were those performed on the gastrointestinal tract, accounting for 60.59% (349) of all reoperations, followed by skin/subcutaneous procedures 14.76% (85), followed by Genitourinary procedures at 8.16% (47). Patients who underwent reoperation were at higher risk for readmission, discharge to a facility, and death (P < 0.01). Conclusion: Reoperation after RC is associated with approximately 5% rate of reoperation within 30 days of surgery. The most common reason for reoperation was related to the gastrointestinal tract, accounting for more than 60% of all reoperations. Risk factors for reoperation included longer surgical times, smoking, obesity, chronic obstructive pulmonary disease, perioperative blood transfusion, and clinically significant hypertension. Knowledge of these factors can aid in operative planning and counseling and lead to possible strategies to reduce reoperations in the early perioperative setting. Ó 2019 Elsevier Inc. All rights reserved.
1. Introduction Bladder cancer is the sixth most common cancer in the United States with an estimated 80,470 new cases and 17,670 deaths in 2019 [1]. Radical cystectomy (RC) along with neoadjuvant chemotherapy is the standard of care for patients with muscle invasive and recurrent high-risk *Corresponding author. Tel.: 617-525-7372; Fax: (617) 525-9894. E-mail address: [email protected] (S.W. Reese). https://doi.org/10.1016/j.urolonc.2019.10.011 1078-1439/Ó 2019 Elsevier Inc. All rights reserved.
noninvasive bladder cancer [2] and is considered one of the most complex and morbid urologic procedures [3−6]. Despite new enhanced recovery after surgery (ERAS) protocols, complication rates remain around 50% and 90-day readmission rates are 30% which is similar to the preERAS era [3,7]. While the literature on postoperative complications after RC is well documented, there is a relative paucity of data on the management of these complications. Reoperation rates have been described at around 5% during the
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postoperative period, however, more detailed investigations into the etiology and risk factors of reoperation after RC have been limited to single-institution studies [8−10]. Understanding the factors that increase the risk of reoperation as well as the types of reoperation is valuable for preoperative planning, patient counseling, and quality improvement. Here, we present a detailed analysis of reoperation after RC using data from the American College of Surgeons-National Surgical Quality Improvement Program (ACS-NSQIP), a large, validated, national dataset. Our study aims to examine the nature of reoperations patients undergo following RC, along with the surgical and patient risk-factors associated with higher reoperation rates. 2. Methods 2.1. Data source and patient selection The current study utilized the ACS-NSQIP database, a large national database that captures risk-adjusted surgical patient data on demographics, medical comorbidities, operative, and postoperative outcome measures [11]. Approximately 400 hospitals participate in ACS-NSQIP and include teaching and nonteaching hospitals, urban and rural alike [12]. A query of the ACS-NSQIP database identified 10, 848 patients undergoing RC from the years 2012 to 2017. We specifically focused on this time period as this was the first-time unplanned reoperations, including the associated reoperation procedures, were included in the dataset. Patients were identified as having undergone a RC using Current Procedural Terminology (CPT) codes 51590, 51595, 51596, 51590, 51595, 51596, 51575, 51570. CPT codes were selected based on prior studies using CPT codes to identify RC patients [13,14]. Patients older than 18 years of age were included in the study. Patients who underwent reoperation for reasons other than for a diagnosis of bladder cancer (ICD-9, 188.x) were excluded from the study. 2.2. Variables and outcomes For each patient, captured variables included demographic, preoperative, operative and postoperative characteristics. Demographic variables included age, sex, body mass index (BMI), American Society of Anesthesiologists physical status (PS), and specific associated medical comorbidities. Preoperative functional status was measured based on a patient’s ability to perform activities of daily living in the 30 days before the procedure, as assessed by a nurse trained to review clinical data specifically for the NSQIP program. The use of chronic steroids was defined as steroid use within the 30 days before and up until the principal operative procedure. Smoking was defined as current smoking within the past year. The principal surgical procedure was RC, with or without a continent diversion. Preoperative laboratory values included creatinine and albumin. Postoperative surgical complications included wound infections,
dehiscence, and bleeding requiring transfusion. Transfusion was defined as at least 1 unit of packed or whole red blood cells starting at the time of surgery up until 72 hours postoperatively. Postoperative medical complications included pneumonia, pulmonary embolism, deep venous thromboembolism, unplanned intubations, acute kidney injury, urinary tract infection, myocardial infarction, stroke, sepsis, and death. We also examined those patients whose hospital length of stay was greater than 30 days, who experienced an unplanned readmission, and patient discharge destinations. The primary outcome was unplanned reoperation within 30 days of the index procedure. NSQIP defines unplanned reoperation as “unplanned return to the operating room for a surgical procedure related to either the index or concurrent procedure performed and may occur at any hospital or surgical facility.” Secondary outcomes included postoperative complications other than reoperation. Reoperations were reported as CPT codes. In order to provide clinically relevant information from the NSQIP CPT-level data, we utilized the Clinical Classification Software procedure categories formulated by the Healthcare Cost and Utilization Project [15]. The Clinical Classification Software procedure categories provide a standardized means of converting CPT or ICD level data into higher-level categorization structures. We further categorized reoperations based on organ system to provide clinically meaningful and interpretable data. 2.3. Statistical analysis Summary statistics of categorical variables were evaluated using Pearson chi-squared test. Multivariable logistic regression analysis was then performed in a stepwise fashion based on univariate analysis to determine associations between patient characteristics and unplanned reoperation. Included in the model, were age, gender, BMI, diabetes, hypertension requiring medication, history of chronic obstructive pulmonary disease (COPD), smoking, steroid use, weight-loss, type of diversion (continent vs. incontinent), American Society of Anesthesiologists physical status, perioperative transfusion, and operative time. All statistical analyses were performed using SAS Studio University Edition (SAS, Charlotte, NC) and a 2-sided significance level was set at P < 0.05. This study was reviewed by the Brigham and Women’s Hospital Institutional Review Board (Boston, MA) and found to be exempt given the deidentified nature of the data. 3. Results 3.1. Patient characteristics and risk factors for reoperation Descriptive characteristics of 10,848 patients who underwent RC with either an ileal conduit or continent diversion are presented in Table 1, stratified based on whether the
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Table 1 Patient characteristics for radical cystectomy, 2012 to 2017. Demographics
Total (n = 10,848)*
No reoperation (n = 10,215)
Reoperation (n = 633)
69 (10.52)
69 (10.5‘4)
69 (10.10)
Age (y) Sex Female Male BMI (kg/m2) <18.5 18.5−24.9 24.9−30 ≥30 Comorbidities Diabetes mellitus Noninsulin (%) Insulin dependent (%) Hypertension Yes COPD Yes Smoker Yes Functional status (%)* Partially dependent Totally dependent Steroid use Yes Weight loss >10% Yes Dyspnea (%) Yes Procedural characteristics Reconstruction Ileal conduit Neobladder ASA class* ASA 2 ASA 3 ASA 4 Mean operative time <50th per. (329 min) 50th−75th per. (330−418 min) 75th−90th per. (419−509 min) >90th per. (510min) Preoperative laboratories Creatinine* Cr ≤1 Cr 1.01 <-> 1.5 Cr > 1.5 Albumin* Alb < 3 Alb 3 <-> 3.99 Alb ≥4 Intra-op blood transfusion Yes
P value
P = 0.66 P = 0.02** 2,559 (23.59) 8,289 (76.41)
2,434 (23.83) 7,781 (76.17)
125 (19.75) 508 (80.25)
248 (2.29) 2,809 (25.89) 4,114 (37.92) 3,677 (33.90)
226 (2.21) 2,652 (25.96) 3,924 (38.41) 3,413 (33.41)
22 (3.48) 157 (24.80) 190 (30.02) 264 (41.71)
1,399 (12.90) 735 (6.78)
1,326 (12.98) 687 (6.73)
73 (11.53) 48 (7.58)
6,482 (59.75)
6,059 (59.31)
423 (66.82)
841 (7.75)
754 (7.38)
87 (13.74)
2,538 (23.40)
2,357 (23.07)
181 (28.59)
180 (1.66) 58 (0.54)
163 (1.60) 52 (0.51)
17 (2.69) 6 (0.95)
401 (3.70)
373 (3.65)
28 (4.42)
318 (2.93)
298 (2.92)
20 (3.16)
898 (8.28)
814 (7.97)
84 (13.27)
9,228 (85.07) 1,620 (14.93)
8,694 (85.11) 1,521 (14.89)
534 (84.36) 99 (15.64)
2,499 (23.16) 7,603 (70.47) 687 (6.37)
2,364 (23.37) 7,172 (70.60) 622 (6.12)
135 (21.39) 431 (68.30) 65 (10.30)
5,496 (50.85) 2,699 (24.88) 1,557 (14.35) 1,096 (10.10)
5,194 (50.85) 2,544 (24.90) 1,466 (14.35) 1,011 (9.90)
302 (47.71) 155 (24.49) 91 (14.38) 85 (13.43)
4,846 (45.91) 4,117 (39.00) 1,593 (15.09)
4,579 (46.07) 3,874 (38.98) 1,486 (14.95)
267 (43.27) 243 (39.38) 107 (17.34)
391 (5.48) 3,061 (42.90) 3,683 (51.62)
361 (5.36) 2,867 (42.61) 3,501 (52.03)
30 (7.39) 194 (47.78) 182 (44.83)
4,100 (37.79)
3,828 (37.47)
272 (42.97)
P < 0.01**
P = 0.44
P < 0.01** P < 0.01** P < 0.01** P = 0.04**
P = 0.32 P = 0.73 P < 0.01**
P = 0.61
P = <0.01**
P = 0.04**
P = 0.20
P = 0.01**
P < 0.01**
* Missing data: Functional Status (31) j ASA (59) j Cr (292) j Albumin (3,713).
patient experienced an unplanned reoperation within 30days of the index operation. The median patient age was noted to be 69 years of age and approximately 76% of patients were male. Overall, 633 (5.84%) of patients
underwent at least 1 unplanned reoperation within 30 days of their index operation. Of those patients who underwent reoperation, 97 (15.32%) underwent at least 1 additional reoperation. On univariate analysis, smoking was
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Table 2 Multivariable analysis of risk factors for reoperation
Age Sex Female Male BMI 18.5−24.9 <18.5 25−30 ≥30 Diabetes No DM1 DM2 Hypertension No Yes COPD No Yes Smoking No Yes Steroid No Yes Weight loss No Yes Neobladder No Yes ASA class ASA 2 ASA 3 ASA 4 Peri-op transfusion No Yes Mean operative time <50th per. 50th−75th per. 75th−90th per. >90th per.
approximately 85% of patients undergoing reconstruction with ileal conduit. On multivariable analysis, we found a number of independent variables to be associated with reoperation. Male sex (OR: 1.36, CI: 1.10−1.67, P = <0.01), smoking (OR: 1.34, CI: 1.11−1.63, P < 0.01), history of COPD (OR: 1.74, CI:1.36−2.23, P < 0.01), perioperative blood transfusion (OR: 1.25 CI: 1.06−1.48, P = 0.01), hypertension requiring medication (OR: 1.34, CI: 1.11−1.62, P <0.01), obesity (BMI≥30) (OR 1.29 (1.04−1.60), P = 0.02 and operative times greater than 90th percentile (OR: 1.41, CI:1.08−1.83, P = 0.02).
OR (95% CI)
P value
1.01 (0.99−1.01)
0.35
1 (ref) 1.36 (1.10−1.67)
− <0.01**
1 (ref) 1.58 (0.97−2.56) 0.81 (0.65−1.01) 1.29 (1.04−1.60)
− 0.07 0.06 0.02**
1 (ref) 0.91 (0.66−1.25) 0.79 (0.61−1.02)
− 0.90 0.18
1 (ref) 1.34 (1.11−1.62)
− <0.01**
1 (ref) 1.74 (1.36−2.23)
− <0.01**
1 (ref) 1.34 (1.11−1.63)
− <0.01**
1 (ref) 1.15 (0.77−1.72)
− 0.48
1 (ref) 0.95 (0.59−1.52)
− 0.82
1 (ref) 1.09 (0.87−1.38)
− 0.46
1 (ref) 0.91 (0.74−1.12) 1.40 (0.99−1.90)
− 0.65 0.07
Approximately 5.84% or 633 patients underwent at least 1 reoperation within 30 days of their index procedure. The median time to reoperation depended on the type of procedure being performed. Vascular/cardiac reoperations occurred closest to the index operation at a median of 6 days, while thoracic/airway procedures occurred furthest in time from the index operation at a median of 21 days (Tables 3A and 3B). Some patients underwent at least 2 or more reoperations, 97 (15.32%) with 68 patients undergoing 2 unplanned reoperations (10.74%) and 29 patients (4.58%) undergoing 3 unplanned reoperations within the 30 days after the index procedure. The most common reoperation procedures were those performed on the Gastrointestinal tract, accounting for 60.59% (349) of all reoperations, followed by skin/subcutaneous procedures 14.76% (85), followed by GU procedures at 8.16% (47), followed by vascular/cardiac procedures 7.12% (41). See Figure 1 and Table 3B for full detail of reoperations.
1 (ref) 1.25 (1.06−1.48)
− 0.01**
3.3. Postoperative complications
1 (ref) 1.04 (0.85−1.28) 1.06 (0.83−1.36) 1.41 (1.08−1.83)
− 0.36 0.58 0.02**
** Signifies significance <0.05.
associated with a significantly higher rate of reoperation compared to nonsmokers (28.59 vs. 23.07%, P = <0.01), along with patients with a diagnosis of COPD (13.74 vs. 7.38%, P < 0.01). Patients with a BMI ≥30 were noted to have higher rates of reoperation (41.71 vs. 33.41%, P < 0.01). Patients who had a longer index operation time, especially those >90th percentile (>510 minutes) (Table 1, P = 0.04) were also noted to have significantly higher rates of reoperation. Other significant findings included functional status, hypertension requiring antihypertensive medication, dyspnea, and male sex (Table 1, P < 0.05). The type of reconstruction did not affect rates of reoperation (Table 1, P = 0.61), with
3.2. Reoperation procedures
In terms of surgical and medical postoperative complications, undergoing an unplanned reoperation was associated with an increased risk of both categories of complications in the postoperative period (Table 4). Patients who underwent reoperation were more likely to have an infectious complication, including superficial infection (10.90 vs. 5.34%, P < 0.01), deep wound infection (9.48 vs. 0.96%, P < 0.01), organ space infection (30.02 vs. 5.66%, P < 0.01) and wound dehiscence (32.86 vs. 0.79%, P < 0.01). Patients with an unplanned reoperation were also more
Table 3A Reoperation characteristics, Freq (%) Reoperation Number of reoperations within 30 days One Two Three
633 (5.84%) 536 (84.68) 68 (10.74) 29 (4.58)
ARTICLE IN PRESS S.W. Reese et al. / Urologic Oncology: Seminars and Original Investigations 00 (2019) 1−9 Table 3B Reoperation procedures (n = 576, 57 missing cpt codes)* Procedure
Freq. (%)
Median days to procedure
Gastrointestinal* Skin/subcutaneous Genitourinary Vascular/cardiac Hernia repair Thoracic/airway Orthopedic CNS Other
349 (60.59%) 85 (14.76%) 47 (8.16%) 41 (7.12%) 27 (4.69%) 12 (2.08%) 8 (1.39%) 2 (0.35 %) 5 (0.89%)
11 12 16 6 11 21 16 8 13
* Includes endoscopy.
likely to die (6.64 vs. 1.59%, P < 0.01), have length of hospital stay >30 days (15.80 vs. 1.06%, P < 0.01), have an unplanned readmission (37.60 vs. 19.88%, P <0.01), and be discharged to a destination that was not their home (38.86 vs. 13.69%, P < 0.01).
4. Discussion In our study, we found that more than 1 in 20 patients (5.84% of the study cohort) underwent at least 1 unplanned reoperation within 30-days of RC for management of bladder cancer and some patients underwent multiple reoperations within this 30-day period. We identified a number of surgical and medical characteristics associated with an increased likelihood of reoperation, including longer operative times and perioperative blood transfusion, along with recent history of smoking, COPD, clinically significant
Fig. 1. Reoperation after cystectomy.
5
hypertension, and obesity. While there is limited reporting of the exact timing of reoperation in the literature [16], we found the median time to reoperation, ranged between 6 and 21 days depending on the category of reoperation. Across all reoperations, procedures on the gastrointestinal tract were the most common operation, accounting for 60.59% of all reoperations within the first 30 days after surgery. The strength of our study lies in its ability to provide a detailed account of the reoperations and complications patients develop after RC using a contemporary dataset from a validated, large national cohort. Our estimate of unplanned reoperation rates after RC is consistent with prior estimates of reoperation in the literature at approximately 5% [8−10,17,18]. A recent study examining complications after RC found that fascial dehiscence, bowel obstruction, and enteric anastomotic leak were the most common reasons for reoperation in the earlier perioperative period [19]. Our study echoes a similar finding in that almost 80% of the reoperations in our study were either gastrointestinal or wound related. With respect to operative characteristics, we found that prolonged operative time and perioperative blood transfusion were associated with increased likelihood of reoperation. One possible explanation for the association between increasing operative length and reoperation is that longer operative times reflect procedural complexity and/or surgeon skill thus predisposing to higher rates of reoperation [20]. However, longer operative times may also be an independent risk factor for perioperative complications, having been demonstrated in the surgical literature to be associated with increased risk of infection, sepsis/shock, prolonged intubation, deep venous thrombosis, impaired wound healing and mortality [21−26]. Prolonged operative times may predispose patients to deleterious side effects of anesthesia, including escalating anesthetic doses, hypothermia, electrolyte derangement, and increased physiologic stress. One potential strategy to minimize operative times is by having these surgeries performed at high-volume centers or with high-volume surgeons which has been associated with decreased rates of perioperative complications [27,28]. The association between perioperative blood transfusion and increased rates of reoperation is likely multifactorial. The need for blood transfusion may suggest clinically significant blood loss and/or postoperative bleeding necessitating return to the operating room. In addition, a well described side effect of blood transfusion is immunosuppression, which exhibits a dose-dependent response to increasing units of blood transfused [29,30]. Downstream consequences of this effect may include increased rates of infection and/or compromised wound healing leading to higher rates of reoperation [31,32]. Indeed, the association between blood transfusion and infectious complication has been described in patients undergoing RC [33−35]. The judicious use of perioperative blood products may lead to
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Table 4 Postoperative complications after radical cystectomy, 2012 to 2017 Complication
Surgical complications Superficial infection Deep wound infection Organ space infection Bleeding Dehiscence Medical complications Pneumonia Pulmonary embolism Unplanned intubation Failure to wean from vent AKI Renal failure UTI CVA Cardiac arrest Myocardial infarction DVT Sepsis Septic shock Death Hosp > 30 days Readmission Discharge destination Home Other
Total (n = 10,848)
No reoperation (n = 10,215)
Reoperation (n = 633)
P value
614 (5.66) 158 (1.46) 768 (7.08) 4,100 (37.79) 289 (2.66)
545 (5.34) 98 (0.96) 578 (5.66) 3,828 (37.47) 81 (0.79)
69 (10.90) 60 (9.48) 190 (30.02) 272 (42.97) 208 (32.86)
<0.01 <0.01 <0.01 <0.01 <0.01
310 (2.86) 194 (1.79) 287 (2.65) 199 (1.83) 148 (1.36) 214 (1.97) 922 (8.50) 60 (0.55) 116 (1.07) 178 (1.64) 299 (2.76) 955 (8.80) 310 (2.86) 204 (1.88) 208 (1.92) 2,269 (20.92)
247 (2.42) 174 (1.70) 202 (1.98) 112 (1.10) 105 (1.03) 185 (1.81) 851 (8.33) 51 (0.50) 95 (0.93) 151 (1.48) 259 (2.54) 802 (7.85) 198 (1.94) 162 (1.59) 108 (1.06) 2,031 (19.88)
63 (9.95) 20 (3.16) 85 (13.43) 87 (13.74) 43 (6.79) 29 (4.58) 71 (11.22) 9 (1.42) 21 (3.32) 27 (4.27) 40 (6.32) 153 (24.17) 112 (17.69) 42 (6.64) 100 (15.80) 238 (37.60)
<0.01 <0.01 <0.01 <0.01 <0.01 <0.01 0.01 <0.01 <0.01 <0.01 <0.01 <0.01 <0.01 <0.01 <0.01 <0.01 <0.01
9,204 (84.85) 1,644 (15.15)
8,817 (86.31) 1,398 (13.69)
387 (1.14) 246 (38.86)
improved surgical outcomes and also minimize the risk of perioperative reoperation [29]. A number of patient characteristics were associated with increased rates of reoperation. Specifically, patients with a history of smoking, COPD, and hypertension requiring medication and obesity (BMI ≥ 30) were associated with higher rates of reoperation. Smoking, COPD, and hypertension likely reflect vasculopathy and decreased ability for optimal tissue oxygenation leading to poor wound healing. Indeed, the association between smoking, infection, poor wound healing, and suppressed immune system is well documented in the surgical literature [36]. Smoking, compromised vascularity, and immunosuppression likely leads to an increased risk of reoperation given increased risk of wound dehiscence, cardiopulmonary-related events, thrombotic events, and infection [37−39]. Smoking-cessation and improvement in cardiopulmonary reserve prior to surgery may represent potentially modifiable risk factors for decreasing rates of reoperation and surgical complications in the perioperative period [37,40,41]. In our study, obese individuals (BMI ≥ 30) were found to have an increased risk of reoperation compared to normal weight individuals. The association between obese individuals and increased rates of surgical complication, including high-grade complications like reoperation has been previously demonstrated in the literature [19,42,43]. Obesity
may increase reoperation rates given obesity likely increases the mechanical tension across the surgical wound, leading to an increased risk of wound dehiscence [16,44]. Obesity and associated metabolic syndrome may lead to compromised wound healing, predisposing to such complications like fascial dehiscence, anastomotic leak, or may impair immunity, leading to increased susceptibility to infectious complications [45]. Indeed, obesity has been associated with an increased risk of infectious complications after RC, likely in some cases necessitating surgical intervention [33,46,47]. Optimizing preoperative weight and nutritional status as well as targeting at-risk populations may serve as an important and implementable way to reduce perioperative reoperation and complication. Patients who underwent a reoperation within 30 days were more likely to experience postoperative medical and surgical complications compared to those patients who did not (Table 4). While we were unable to link causality, a priori reasoning would suggest that in some cases, like wound dehiscence, this may have been an indication for surgery, while in others, like postoperative pneumonia, this may have resulted from undergoing reoperation. Despite being unable to ascertain causality, we found the burden of reoperation and associated complications is considerable and highlighted by the higher rates of death, unplanned readmission, prolonged length of hospital stay, and discharge to
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facility other than home. Unplanned readmissions after RC is associated with increased patient mortality after RC and increased rates of postoperative complications [48−50]. Identification of patients who are at risk for reoperation and targeted interventions to reduce reoperation may be an important way of reducing postoperative readmission and mortality. Our study highlights risk factors associated with unplanned reoperation after RC. Along a spectrum, important drivers of reoperation after RC include both modifiable and nonmodifiable risk-factors. For modifiable risk factors, preoperative interventions that can address a patient’s obesity or aid in smoking cessation and/or cardiopulmonary reserve may have the potential to reduce the rates of reoperation in patients undergoing RC and the subsequent sequelae of unplanned hospital readmission, prolonged hospital stays, and nonhome discharges. For nonmodifiable risk factors, increased adoption of preoperative risk assessment would be beneficial. Identifying high-risk patients who are more likely to undergo reoperation or fare-worse after surgery would benefit from preoperative planning that would anticipate and direct intraoperative and postoperative resources to aid and risk-mitigate this population. Such interventions could include preoperative physical rehabilitation, enhanced and tailored antibiosis for patients at risk for postoperative infections, and directing anticipatory resources to patients in need in the postoperative setting. Such preoperative risk assessment tools could also be helpful in identifying which patients would benefit from ERAS protocols and identifying those patients who would not benefit, instead of applying a “one size fits all” approach to postoperative recovery. Several limitations of the study warrant further discussion. First, our study was performed in a retrospective manner and along with the deficiencies associated with a retrospective study design, we were not able to capture important variables of interest. For example, we were not able to distinguish if patients had received neoadjuvant chemotherapy as this variable is no longer collected in NSQIP. Conceivably, patients who received neoadjuvant chemotherapy could be at higher risk for postoperative complications and thus also at risk for reoperation. Yet, studies have not shown significantly higher postoperative complication rates for patients receiving neoadjuvant chemotherapy compared to patients who had upfront RC, however these studies do not focus on reoperation specifically [51,52]. Next, we were unable to distinguish between a minimally invasive vs. open approach as there currently do not exist CPT codes to capture this distinction. Robotic cystectomies have been postulated to take longer time and may be associated with a higher learning curve. Our analysis was limited to the 30-days postprocedurally, thus limiting the scope of the study to immediate postoperative outcomes. However, reoperations have been reported beyond the 30-day period, thus our study likely underestimates the true incidence of reoperations and may not capture the types of reoperations
7
that occur in a delayed fashion [10]. In addition, smaller, nonoperative procedures such as need for bedside incision and drainage or interventional radiology procedures are not captured but would represent an invasive intervention nonetheless. The specific reason for reoperation must be extrapolated from diagnosis codes leaving a degree of imprecision. Surgical volume, pack years of smoking, history of prior abdominal surgery, and clinicopathologic data such as tumor stage, grade, and histologic subtype were not documented in the database and thus could not be accounted for. Similarly, we could not control for hospital level data such as hospital volume, geographic location, or other sociodemographic data that may have influenced the outcome. 5. Conclusion In conclusion, we found the overall reoperation rate to be 5.84% within the first 30 days of RC and risk factors for reoperation included long operative times, male sex, perioperative blood transfusion, smoking, obesity, COPD, and clinically significant hypertension. An understanding of the relationship between patients who undergo RC and the kind of reoperations patients are most likely to experience is important in preoperative counseling, operative planning, and risk-stratification. This knowledge is imperative in directing efforts to reduce reoperation, mitigate postoperative complication, and improve patient outcomes. Supplementary materials Supplementary material associated with this article can be found in the online version at https://doi.org/10.1016/j. urolonc.2019.10.011. References [1] Siegel RL, Miller KD, Jemal A. Cancer statistics, 2019. CA Cancer J Clin 2019;69:7–34. https://doi.org/10.3322/caac.21551. [2] Stein JP, Lieskovsky G, Cote R, Groshen S, Feng AC, Boyd S, et al. Radical cystectomy in the treatment of invasive bladder cancer: longterm results in 1,054 patients. J Clin Oncol 2001;19:666–75. https:// doi.org/10.1200/JCO.2001.19.3.666. [3] Djaladat H, Katebian B, Bazargani ST, Miranda G, Cai J, Schuckman AK, et al. 90-Day complication rate in patients undergoing radical cystectomy with enhanced recovery protocol: a prospective cohort study. World J Urol 2017;35:907–11. https://doi.org/10.1007/s00345-0161950-z. [4] Daneshmand S, Ahmadi H, Schuckman AK, Mitra AP, Cai J, Miranda G, et al. Enhanced recovery protocol after radical cystectomy for bladder cancer. J Urol 2014;192:50–6. https://doi.org/ 10.1016/j.juro.2014.01.097. [5] Hautmann RE, de Petriconi RC, Volkmer BG. 25 years of experience with 1,000 neobladders: long-term complications. J Urol 2011;185:2207–12. https://doi.org/10.1016/j.juro.2011.02.006. [6] Mossanen M, Gore JL. The burden of bladder cancer care. Curr Opin Urol 2014;24:487–91. https://doi.org/10.1097/MOU. 0000000000000078. [7] Semerjian A, Milbar N, Kates M, Gorin MA, Patel HD, Chalfin HJ, et al. Hospital charges and length of stay following radical
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