Urinary diversion for benign indications is relatively uncommon and may be performed with or without a concomitant cystectomy. Urinary diversion is typically considered a last-resort option for managing persistent neurogenic lower urinary tract dysfunction (NLUTD) when maintaining bladder integrity is no longer feasible, and protecting the kidneys becomes the primary concern [1].

Cystectomies for benign etiologies makes up a small percentage (~8%) of all cystectomies performed. Given this small patient population, there is limited data regarding the perioperative morbidity and mortality rates for simple cystectomies, derived mainly from small cases series [2,3]. Additionally, these case series include large heterogenous groups with many indications such as radiation cystitis, interstitial cystitis, recurrent fistula formation, recurrent urinary tract infections etc. Recent reports from single-institution case series suggest the complication rates for urinary diversions for benign causes range from 39% to 73% depending on the complication [4]. However, it is unclear if these rates differ among the specific indications for their diversion.

A common complication of these procedures is delayed return of gastrointestinal (GI) function. Alvimopan, an opioid receptor antagonist, is frequently used in such cases as it has been shown to reduce the incidence of postoperative ileus and shorten the time required for the return of bowel function in the nonneurogenic population [5,6]. However, it has not been studied in NLUTD patients where the impact of neurogenic dysfunction may negate the effectiveness of this intervention. Understanding the postoperative benefits, or lack thereof, of alvimopan may help better inform surgeons about the appropriate use of this relatively expensive intervention.

Other factors that can influence surgical outcomes include the chosen surgical approach. The use of robotic surgery is becoming increasingly common for cystectomies. While extensive research has explored the outcomes of robotic versus open surgery in the context of cancer-related cystectomy, the efficacy and outcomes of robotic surgery in the NLUTD population have yet to be evaluated. Surgical approach may impact postsurgical outcomes including infection rates and recovery time. Finally, this procedure is distinct in that it can involve multiple surgeons. The impact of using a single-surgeon approach versus a multisurgeon team—where one surgeon performs the cystectomy, and another manages the diversion—has also not been studied in this specific population. The team composition may impact operative and recovery time in patients, making it an important aspect to study. Understanding postoperative outcomes of both robotic versus open cases and single versus multiple-surgeon cases can help surgeons make decisions to optimize patient care. In addition, not every institution has access to the resources and capital to offer robotic surgery or maintain multiple-surgeon teams, highlighting the need to ensure optimal patient outcomes even without this infrastructure.

Therefore, we sought to study the use of alvimopan, robotic versus open surgical approaches and the use of a single versus multiple surgeons to complete the procedure to comprehensively assess peri- and postoperative outcomes in neurogenic patients undergoing simple cystectomy.

We conducted a retrospective analysis of simple cystectomies at our institution from 2011–2022. Our study was approved by the Institutional Review Board of University of Texas Southwestern (IRB number: STU-2024-1296). We included all patients who underwent a simple cystectomy due to the diagnosis of NLUTD. Selection criteria for the procedure included patients that had a diagnosis of NLUTD that had failed other treatment modalities or were unsuitable to undergo other treatment plans. The risks and benefits of the procedure were thoroughly explained to the patient.

All cystectomy procedures were performed by experienced surgeons. All surgical decisions including whether to have a single versus multiple-surgeon panel and the use of alvimopan were up to the discretion of the surgeon. An expedited recovery after surgery (ERAS) framework was followed perioperatively and standard postoperative care follow-up procedures were adhered to including patient optimization, early mobilization, early feeding, and opioid-sparing pain control. However, the decision for alvimopan use was left up to the surgeon. A 6-week follow-up visit was scheduled for patients to address any concerns with the stoma and appliance, and visits at 3–6 months as well as 1 year postoperatively were planned.

Patient demographic and perioperative variables such as age, sex, body mass index (BMI), diagnosis that led to NLUTD, number of surgeons, alvimopan use, and surgical approach amongst others were gathered. We also measured postoperative variables such as time to return of bowel function, postoperative ileus, nasogastric tube (NGT) use, and total parenteral nutrition (TPN) use were extracted from medical records. The aforementioned factors were also included as a conglomerate known as “postoperative complications.”

Data were represented as median and interquartile range for continuous variables, and number (%) for categorical variables. Statistical analyses were conducted using STATA 17 (StataCorp LLC, USA). Mann-Whitney U-tests, chi-square tests, and Fisher exact tests were utilized to study the data. A 2-tailed P-value threshold of 0.05 was considered statistically significant for all comparisons.

A total of 44 patients were included in the study, with 31 (70.4%) being female. The median age of the cohort was 57 years (interquartile range [IQR], 28.4–86.4), and the median BMI was 28.3 (range 14.4–42.2) kg/m². Most patients were Caucasian (n=37, 84%), and n=3 (6.8%) identified as Hispanic. Regarding underlying conditions contributing to NLUTD, 26 patients (59%) had spinal cord injuries, 6 (13%) had multiple sclerosis, 3 (6.8%) had spina bifida, 3 (6.8%) had a stroke, 1 (2.2%) had methicillin-resistant Staphylococcus aureus septicemia that led to NLUTD, 1 (2.2%) had an intracranial mass that was treated with surgery, chemotherapy and radiation which led to NLUTD. There was also 1 (2.2%) patient that had recurrent UTIs and 2 patients (4.5%) that had vesicoureteral reflux and severe hydronephrosis (Table 1).

When comparing robotic and open surgery groups, no significant differences were observed in operative time (P=0.65), estimated blood loss (EBL) (robotic: 300 [IQR, 200–455] mL; open: 350 [IQR, 163–603] mL), length of stay (LOS) (robotic: 6 [IQR, 5–8] days; open: 6 [IQR, 6–9.5] days), return of bowel function (as measured by patient-reported flatus) (robotic: 3 [IQR, 2–4] days; open: 3 [IQR, 3–4.8] days), or perioperative complications including ileus (measured as >3-day postoperation for return of bowel function) (robotic n=2, open n=1) (Supplementary Table 1A and B).

Of the 44 patients, 13 (29.5%) had a single surgeon perform their procedure, while 31 (69%) had multiple surgeons. There were no significant differences in age (single: 56.0 [IQR, 52.0– 63.0] years; multiple: 60.0 [IQR, 49.0–66.0] years), BMI (single: 26.8 [IQR, 23.1–33.5] kg/m²; multiple: 26.7 [IQR, 23.4–33.0] kg/m²), or operative time (single: 295 [IQR, 242–348] minutes; multiple: 298 [IQR, 232–368] minutes) (Fig. 1A, Supplementary Table 2A). However, EBL was significantly higher in the multiple-surgeon group (375 [IQR, 238–575] mL) compared to the single-surgeon group (200 [IQR, 125–300] mL, P=0.008) (Fig. 1B, Supplementary Table 2B). No significant differences were found in LOS, return of bowel function, or perioperative complications (Fig. 1C, Supplementary Table 2B).

Thirty-two patients (73%) received alvimopan, while 12 (27%) did not. There were no significant differences in age (alvimopan: 57.5 [IQR, 49.0–64.0] years; nonalvimopan: 61.0 [IQR, 54.0–63.0] years) or BMI (alvimopan: 26.5 [IQR, 24.0– 33.0] kg/m²; nonalvimopan: 24.6 [IQR, 21.0–27.0] kg/m²) (Supplementary Table 3A). Perioperative factors were similar between the 2 groups, with no significant differences in operative time (alvimopan: 297 [IQR, 237–349] minutes; nonalvimopan: 289 [IQR, 244–355] minutes), EBL (alvimopan: 300 [IQR, 200–300] mL vs. nonalvimopan: 175 [IQR, 138–320] mL), LOS (alvimopan: 6.00 [IQR, 5.00–8.00] days; non-alvimopan: 8.00 days [IQR 6.00–15.00]), return of bowel function (alvimopan: 3.00 days [IQR 2.00–4.00]; nonalvimopan: 3.00 [IQR, 3.00– 7.00] days), or perioperative complications (alvimopan: n=2; nonalvimopan: n=2) (Fig. 2, Supplementary Table 3B). Since there are currently no ERAS guidelines for simple cystectomy, alvimopan prescription was based on surgeon preference. All patients who received alvimopan received the same dose.

We conducted a retrospective cohort analysis of patients undergoing simple cystectomy for NLUTD between 2011 and 2022 at our institution. Our analysis revealed that procedures involving multiple-surgeon panels were associated with a higher EBL of approximately 175 mL compared to single-surgeon procedures, while all other intra- and postoperative outcomes were similar regardless of the presence of one or multiple surgeons. No significant differences were observed between robotic and open approaches in operative or postoperative factors, including operative time, LOS, or perioperative complications. Similarly, there were no statistically or clinically significant differences between patients who received preoperative alvimopan and those who did not in terms of ileus rates, return of bowel function, use of TPN, or NGT.

To our knowledge, this is the first contemporary American study that analyzes surgical approach, number of surgical panels, and alvimopan use in patients diagnosed with NLUTD undergoing simple cystectomy. Open versus robotic cystectomy has been extensively compared in patients undergoing radical cystectomy for bladder cancer management and have consistently demonstrated that robotic surgery is noninferior to open surgery [7]. A large multi-institutional American study found that robotic cystectomy was associated with a decreased risk of 30-day mortality, but no other significant differences [8]. A single-institution study conducted by Haudebert et al. [9] from 2004 to 2020 examined the differences in surgical approaches— open, laparoscopic, and robotic—in patients undergoing simple cystectomy. They found that patients in the open (9.7%) and laparoscopic (7.7%) groups had a higher risk of postoperative evisceration compared to the robotic group (0%) [9]. Additionally, while the robotic cohort (5.8%) had a higher likelihood of urinary leaks compared to the laparoscopic (0%) and open (3.2%) groups, this difference was not clinically significant [9]. The robotic surgery group (0%) also experienced fewer bowel complications compared to the open (6.5%) and laparoscopic (7.7%) groups, although this difference was not statistically significant [9]. The incongruence of this study from our results may be due to the different levels of surgeon experience.

Simple cystectomy with urinary diversion can be performed by a single surgeon or by a team of 2 or more surgeons, with one team handling the cystectomy portion and another performing the reconstruction. Our study found that procedures involving multiple surgeons were associated with a statistically significant increase in EBL compared to those performed by a single surgeon. However, there was no difference in the rate of blood transfusions between the 2 groups. The elevated EBL in the multiple-surgeon group may be due to the combined blood loss estimates from multiple surgeons, as opposed to a single surgeon providing one unified estimate for the entire procedure [10]. There may also increased procedural complexity in a multiple-surgeon case contributing to an increased overall EBL. A retrospective single-institution study conducted from 1999 to 2002 examined the cost, perioperative, and postoperative changes associated with one-versus multiple-surgeon radical cystectomy. The study found a statistically significant reduction in operative time for the multiple-surgeon team, with both ileal conduit creation (121 minutes shorter) and neobladder construction (149 minutes shorter) [11]. However, neobladder patients who had a multiple-surgeon team experienced a significantly longer LOS (14 days vs. 11 days for the single-surgeon team, P=0.008) [11]. The differences between this study and ours can be attributed to variations in surgical methods, as all cases in the study of Ludwig et al. [12] are likely open procedures, given the study’s time frame. The impact of using multiple surgeons may be more noticeable in open procedures, due to the increased physical demands of pelvic surgery, compared to robotic surgery. Additionally, the patient populations differ, as our study focused on benign cases, while theirs looked at malignant diagnoses, which can affect anatomy, operative time, postoperative complications, and, ultimately, LOS.

Alvimopan was first studied in patients undergoing partial bowel resection in patients also receiving patient-controlled analgesia with opioids. In this placebo-controlled phase III trial, administration of preoperative alvimopan followed by twice daily postoperative use decreased the time to return of bowel function (as measured by toleration of first solid food and first bowel movement) and length of hospital stay [12]. Postoperative ileus was also decreased in patients that were assigned to receive alvimopan [12]. Notably, there was no significant difference in opioid consumption between the 2 cohorts [12]. In the urological setting, alvimopan is commonly used as a gut motility stimulator in patients undergoing radical cystectomy with urinary diversion and has consistently shown an earlier return of bowel function. In 2016 Cui et al. [6] completed a systematic review and meta-analysis of radical cystectomy patients that received alvimopan. Looking at 613 patients, 294 (47%) of whom received alvimopan they observed that use of the drug reduced time to toleration of clear liquids (hazard ratio [HR], 1.34; 95% confidence interval [CI], 1.19–1.51; P<0.001), time to toleration of solid foods (HR, 1.22; 95% CI, 1.11–1.34; P<0.001), time to first bowel movement (HR, 1.27; 95% CI, 1.12–1.43; P<0.001), and LOS (HR, 1.17; 95% CI, 1.10–1.25; P<0.001) [6]. However, the use of alvimopan in patients with NLUTD undergoing simple cystectomy with urinary diversion have not been well-studied. Particularly, in neurogenic patients the etiology of neurogenic bowel is poorly understood. It is clear in rate models that functional and molecular remodeling occurs after spinal cord injury; however, the mechanism is unclear [13]. Given alvimopan does not directly initiate or increase bowel motility on its own, as it is a peripherally acting mu-opioid receptor antagonist, it is not unreasonable to see that alvimopan may not have as robust an effect on bowel function on this population. In our cohort, we observed no differences in time to return of bowel function or incidence of postoperative ileus between patients who received alvimopan and those who did not. In multiple single-institution case series studying radical cystectomy, alvimopan accelerated the return of bowel function by at least 24 hours; however, we observed that the median time to return of bowel function for both groups was similar (3 days for both groups) [12,14,15]. In Ludwig et al., [12] radical cystectomy patients who received alvimopan had a decreased LOS by 1 day (P<0.001); while we also observed a decrease in the LOS of alvimopan patients, this was not at a level of significance (P=0.21) however this needs to be interpreted cautiously given the short LOS. We hypothesize that the presence of neurogenic bowel in these patients may diminish the clinically significant effects of alvimopan [6]. Furthermore, patients undergoing radical cystectomy are usually exposed to opioids primarily in the context of surgery (barring any comorbidities or surgeries that may expose them to opioids). However, given the heterogeneity of the NLUTD population undergoing simple cystectomy, there is a high variability of the utilization of opioids in this patient group. This difference in length of opioid exposure may further contribute to the decreased effectiveness of alvimopan on GI motility of simple cystectomy patients [16,17].

Our study has several limitations, including its retrospective design and single-institution setting, which limit the generalizability of our findings. Specifically, the retrospective design introduces the potential for selection bias. Furthermore, due to the highly specialized procedure in a niche population our sample size was limited. Notably, in our study the robotic cases were more frequently performed by a multiple surgeon team which may lead to confounding of data such as EBL, infection rate, and LOS between the 2 groups. Our cohort was homogenous with the majority of patients identifying as Caucasian and female. Additionally, the heterogeneity of diagnoses leading to NLUTD in our cohort, along with varying degrees of GI dysfunction based on the timing of initial diagnosis, may have contributed to variability in the effects of alvimopan.

In conclusion, patients with NLUTD undergoing simple cystectomy are a unique cohort. Multiple surgeons were linked to higher blood loss, but did not affect other outcomes. Interestingly, alvimopan did not significantly impact bowel function recovery or postoperative ileus, likely due to the impact of neurogenic disease on the return of bowel motility.