|Year : 2022 | Volume
| Issue : 2 | Page : 44-51
The absence of urinary diversion in radical cystectomy avoids early complications in hemodialysis patients
Yun-Ta Yang1, Jui-Ming Liu2, Cheng-Feng Lin1, Kuan-Lin Liu1, Cheng-Chia Lin1, Chun-Te Wu1
1 Division of Urology, Department of Surgery, Chang Gung Memorial Hospital, Keelung, Taiwan
2 Division of Urology, Department of Surgery, Taoyuan General Hospital, Ministry of Health and Welfare, Taoyuan, Taiwan
|Date of Submission||16-Jan-2022|
|Date of Decision||14-Feb-2022|
|Date of Acceptance||08-Apr-2022|
|Date of Web Publication||25-Apr-2022|
No. 222, Maijin Road., Anle Dist., Keelung City 204
Source of Support: None, Conflict of Interest: None
Background: Patients with end-stage renal disease who receive dialysis are considered a high-risk group for perioperative complications following anesthesia and surgery. However, for patients with anuria who will undergo radical cystectomy (RC), a urinary diversion is unnecessary. This study aimed to identify a safe surgical strategy by comparing oncologic outcomes and early complication rates in dialysis and nondialysis patients after RC.
Materials and Methods: This study included 85 patients with primary urothelial cell carcinoma of the bladder who underwent RC at the Chang Gung Memorial Hospital, Keelung, Taiwan. Twenty-eight of these patients underwent regular hemodialysis. Overall survival and recurrence-free survival were compared to evaluate the oncologic outcomes. Complications at 3 months were graded using the Clavien–Dindo classification.
Results: The overall survival and recurrence-free survival differences between dialysis and nondialysis patients were not significant (P = 0.686; P = 0.528). The degree of muscle-invasive disease was an independent factor affecting overall survival. The overall complication rates in the dialysis and nondialysis groups were 36% and 84%, respectively (P < 0.001). The major complication (Grades III–V) was 16% in the dialysis group and 28% in the nondialysis group (P = 0.241). The most common early complications were urinary tract infection and bowel kinetics change, and both were significantly lower in the dialysis group. A lower re-admission rate was also observed in the dialysis group.
Conclusion: Lower rates of early complications and acceptable survival outcomes were observed in dialysis patients. Surgery can be conducted more aggressively, with confidence in suitable cases.
Keywords: Bladder urothelial carcinoma, end-stage renal disease, hemodialysis, radical cystectomy, urinary diversion
|How to cite this article:|
Yang YT, Liu JM, Lin CF, Liu KL, Lin CC, Wu CT. The absence of urinary diversion in radical cystectomy avoids early complications in hemodialysis patients. Formos J Surg 2022;55:44-51
|How to cite this URL:|
Yang YT, Liu JM, Lin CF, Liu KL, Lin CC, Wu CT. The absence of urinary diversion in radical cystectomy avoids early complications in hemodialysis patients. Formos J Surg [serial online] 2022 [cited 2022 May 26];55:44-51. Available from: https://www.e-fjs.org/text.asp?2022/55/2/44/343813
| Introduction|| |
Urothelial bladder cancer is known to have a high recurrence rate, with some cases ultimately leading to urinary bladder loss. Although novel therapies and bladder-preserving surgery have become popular, the current guidelines still recommend radical cystectomy (RC) for nonmetastatic muscle-invasive bladder cancer and specific nonmuscle-invasive high-grade disease. However, high complication rates for urinary diversion (UD) after RC have been widely documented in the literature,,, which has made some patients hesitant in undergoing aggressive treatment.
Among patients with urothelial carcinoma, some with end-stage renal disease are receiving long-term dialysis. In Taiwan, Lin et al. documented a bladder cancer incidence rate of 2.12 per 1000 person-years among the dialysis population, with an adjusted subdistribution hazard ratio of 41.95 to the nondialysis population. This correlation was also observed in the United States population with a standardized incidence ratio of 1.57. According to the Annual Report on Kidney Disease in Taiwan, the dialysis population increased from 1448 to 3480/million from 2000 to 2017, approximately 0.4% of the population, with a 5-year survival rate of 54.6%. Based on the growing dialysis population, increasing the number of patients with bladder cancer who undergo dialysis might pose a challenge to urologists.
In practice, patients undergoing dialysis are at higher risk when administering anesthesia. They are expected to experience more complications due to high American Society of Anesthesiologists (ASA) grading and are of a relatively more immunocompromised status. When performing RC on dialysis patients, UD is often unnecessary for those with anuria or oliguria. Consequently, RC may be a practical choice for patients undergoing dialysis.
Our study compared the outcomes following RC for chronic dialysis patients and nondialysis patients with bladder cancer. These results may provide a reference for prognosis and decision-making. This study also identified the early complications of surgery, most of which were associated with UD rather than the cystectomy procedure.
| Materials and Methods|| |
Medical records were collected from the Chang Gung Memorial Hospital, and the study was approved by the Chang Gung Medical Foundation Institutional Review Board (approval number: 202100186B0). The study enrolled 85 patients with urothelial cell carcinoma of the bladder who underwent RC at the Chang Gung Memorial Hospital, Keelung, Taiwan, between April 1, 2006, and March 31, 2016. The surgical indications of RC in all patients were detrusor muscle-invasive disease proved by transurethral tumor pathology, or high-risk nonmuscle-invasive diseases including repeated recurrent T1/Tis disease, high-grade, or multifocal tumor. Image studies including computed tomography (CT) or magnetic resonance imaging were evaluated for identifying a surgical resectable local disease, and metastatic diseases were excluded. Among these patients, 28 had end-stage renal disease and received regular hemodialysis. One patient who had been receiving dialysis for <6 months and two patients with residual urine output and who underwent UD were excluded. Finally, 82 patients were included in the statistical analysis [Table 1].
|Table 1: Characteristics of the patients who received radical cystectomy|
Click here to view
All bladder specimens were examined by pathologists at the Chang Gung Memorial Hospital. The pathology reports were reviewed and staged according to the bladder cancer TNM staging system of the Cancer Staging Manual, Eighth Edition, published by the American Joint Committee on Cancer (2017).
Surgeries were performed by a single experienced urologic surgeon. RC with pelvic lymph node dissection was performed through laparotomy, laparoscopy, or robotic-assisted laparoscopy methods, depending on the individual. Concurrent nephroureterectomy in the case of preoperative evidence of upper urinary tract involvement was performed in 14 (56%) dialysis patients and 3 (5%) nondialysis patients. None of the dialysis patients underwent UD, whereas 9 nondialysis patients underwent ureterocutaneostomy, 34 underwent an ileal conduit UD, and 14 underwent Studer orthotopic neobladder reconstruction [Table 1].
The primary endpoint of the study was to determine the overall survival and recurrence-free survival of the dialysis and nondialysis groups. The patients underwent clinical follow-up in the 1st, 3rd, and 6th postoperative months and then every 6 months for stability. The second endpoint was to monitor and assess the perioperative complications. Complications were evaluated during the admission period and in the outpatient department after discharge. The severity of complications was graded using the Clavien–Dindo classification. Early complications were defined as any complications recorded 3 months after RC. According to the classification, major complication definitions were complications that need surgical, endoscopic, or radiologic intervention; life-threatening conditions requiring intensive care; or death. All patients were evaluated by oncologist for receiving neoadjuvant or adjuvant chemotherapy, with general inclusion criteria of T3, T4 or node positive disease. The Eastern Cooperative Oncology Group performance status ≤2 was necessary. Patients were excluded from chemotherapy for a relative criterion of estimated glomerular filtration rate <60 mL/min/1.73 m2 and any other comorbidity that the physician judged to be incompatible. There were 22 (38.6%) nondialysis patients who received at least one chemotherapy, while none of the dialysis patients did. CT was performed in the 6th month for patients with pathologic-positive lymph nodes and in the 12th month for node-negative patients; follow-up imaging was repeated as clinically indicated. The median follow-up time for the patients was 36.6 months (interquartile range, 63.8 months; longest, 126 months).
Patient data were processed using the SPSS version 22.0 (IBM Corp., 2013. IBM SPSS Statistics. Armonk, NY: IBM Corp.). Nonparametric statistics were used in this study. Statistical differences between groups were examined using the Pearson's Chi-square test for categorical variables and the Mann–Whitney U-test for continuous variables. Post hoc comparisons were conducted using the Dunn's test. Survival was counted from the surgery date to death or recurrence event. Censored data were calculated according to the last medical record. The 5-year overall survival and recurrence-free survival were presented using the Kaplan–Meier curve, which was graphed with R studio version 1.2.5019. (RStudio Team, 2019. RStudio: Integrated Development for R. Boston, MA). Significance was verified using log-rank tests. Statistical significance was set at P < 0.05. Multivariable analysis was adjusted for confounding factors, including age, sex, dialysis status, muscle-invasive cancer, and synchronous upper urinary tract cancer, which have distribution differences between the two study groups. The effect estimates were presented as a Cox proportional hazard model.
| Results|| |
Characteristics and perioperative outcome
The age distribution of the groups did not differ significantly (P = 0.615). More men (75%) were in the nondialysis group than in the dialysis group, but the difference was not significant (P = 0.078). In addition, the ASA score was significantly higher in the dialysis group (P < 0.001) because the presence of dialysis was categorized as ASA 3 as comorbidity. More patients also presented with muscle-invasive disease in the nondialysis group (P < 0.001). Both groups included positive lymph node cases, while no patients with stage IV disease were found in the dialysis group. High-grade tumors accounted for most of the cases in both groups, and dialysis groups had more multifocal pathology though without statistics difference.
There were 22 nondialysis patients receiving either neoadjuvant or adjuvant chemotherapy. Among these patients, eight patients had neoadjuvant chemotherapy. Six of eight patients received Gemcitabine-cisplatin regimen, and the other two received cisplatin–methotrexate–vinblastine regimen. The mean duration from the last dosage to surgery was 48 days. In patients with evidence of upper urinary tract involvement, 56% of dialysis patients received concurrent unilateral or bilateral nephroureterectomy, whereas only 7% of nondialysis patients received concurrent surgery.
Perioperative outcomes were documented, with the concurrent nephroureterectomy cases excluded [Table 2]. The pelvic lymph node dissection number and blood loss amount did not differ significantly between the groups. Dialysis patients also spent less time in laparotomy surgery than their nondialysis counterparts. In addition, the dialysis group spent a shorter time in the hospital than the nondialysis group (P = 0.003).
The overall survival between the dialysis and nondialysis groups showed no significant difference [log-rank test, P = 0.686; [Figure 1]], and the 5-year survival rates of the dialysis and nondialysis groups were 55%. The recurrence-free survival showed no significant difference (log-rank test, P = 0.528), with 5-year survival rates of 53% and 47%, respectively.
|Figure 1: The overall and recurrence-free Kaplan–Meier survival curve of dialysis and nondialysis patient groups|
Click here to view
The multivariable analysis revealed that the independent factors associated with overall survival were muscle-invasive disease (hazard ratio, 2.75; 95% confidence interval, 1.09–6.94; P = 0.032). Dialysis status, sex, age, and synchronous upper urinary tract cancer had no significant effects on survival outcomes [Table 3].
|Table 3: Multivariable analysis of overall survival in patients having radical cystectomy|
Click here to view
Outcome of early complications
Surgical complications were recorded for 3 months postoperatively. The overall complication rates in the dialysis and nondialysis groups were 36% and 84%, respectively [P < 0.001; [Table 4]a]. The major complication (Grades III–V) rates were 16% in the dialysis group and 28% in the nondialysis group (P = 0.241). Among these cases, no Grade IV or V complications were recorded in the dialysis patients. Four Grade IV complication events occurred in nondialysis patients, including two cerebral vascular accidents and two acute myocardial infarctions. Four nondialysis patients died, two from sepsis resulting from urinary tract infection, one from pneumonia, and one from severe intra-abdominal infection. The details of complication events had been documented [Table 4]b.
No urinary tract infections such as pyelonephritis were observed in the dialysis group postoperatively. The urinary tract infection rate was 0% in the dialysis group and 42% in the nondialysis group (P < 0.001). Other urinary tract complications consisted of two cases of asymptomatic hydronephrosis in the dialysis group. In the nondialysis group, patients experienced incontinence, prolonged hematuria, and calculus.
For the gastrointestinal system, the complication rate was 8% and 28% in the dialysis and nondialysis groups, respectively (P = 0.043). For most of the patients, common complaints were ileus or prolonged constipation requiring frequent laxative use. The rates of wound or intra-abdominal infection were 12% and 14% in dialysis and nondialysis patients, respectively. In the nondialysis group, complications related to UD included ileal conduit hemorrhage, ileal conduit obstruction, and neobladder leakage. Complication-related admission rates were 28% and 54% (P = 0.011) in the dialysis and nondialysis groups, respectively. In the subgroup analysis in nondialysis patients, neoadjuvant chemotherapy groups had a general complication rate of 63% while 88% in other patients. The complications were less in the neoadjuvant group, while there was no statistical difference both in general (P = 0.069) and major complications (25% and 29%, respectively, P = 0.835).
| Discussion|| |
UD has been reported to have high complication rates. Anderson and McKiernan indicated that overall early complication rates in RC with UD were 49%–64%, with major complication rates of 13%–22%. In our study, we observed an overall complication rate of 84% in nondialysis patients with UD, which was significantly higher than the 36% of dialysis patients recorded. Although not significantly different statistically, nondialysis patients seemed to be at a higher risk of major complications than dialysis patients. Anderson and McKiernan discovered that the most common early complications of UD were related to the gastrointestinal tract and infection, which was consistent with our results for the nondialysis group but not for the dialysis group. Sporadic cardiovascular events and cerebrovascular accidents were observed in nondialysis patients with an ileal conduit. Dialysis patients were known for a higher risk of perioperative cardiovascular events and coagulopathy; the effect was not observed in our study nonetheless. However, the nondialysis patients with these complications had a relevant underlying history. One myocardial infarction case had a history of acute infarction 10 years ago without continuous follow-up, and the other case was diagnosed with left anterior descending coronary artery occlusion before. One cerebrovascular accident case had contralateral lacunar infarction 1 year ago, and the other case had poorly controlled hypertension and a recent focal limb weakness. Considering the negative statistical difference and small case number in the study, the interpretation of this result should be more conservative.
By comparing the early complications between the two groups, an approximately 50% increase in all complications and a 12% increase in major complications related to UD could be estimated. Clinically, we observed frequent long-term complications of UD, including ureteric obstruction, conduit stenosis, local skin erosion, renal function compromise, and repeated urinary tract infection, which bothered the patients and decreased their quality of life. Although orthotopic neobladder had recently been the more often chosen method of diversion, patient quality of life had not improved much compared with patients receiving an ileal conduit. Moreover, whether these complications shorten a patient's life expectancy remained unknown. Without UD being necessary, operations took less time with less blood loss in the dialysis group in both surgical approaches of laparotomy and minimally invasive laparoscopy. Hospital stays were also shorter.
Bladder cancer treatment in patients undergoing dialysis is controversial. Wu et al. contended that one-step bilateral concurrent nephroureterectomy confers a survival benefit for dialysis patients due to the metachronous or undetectable multiple, early synchronous tumors in the urinary tract. The issues of concurrent nephroureterectomy for dialysis patients emerged. Kang et al. found no survival benefit related to prophylactic one-step total exenteration surgery in upper urinary tract cancer, while prophylactic cystectomy was still suggested. Similarly, Tseng et al. reported a survival benefit in patients who received concurrent nephroureterectomy with RC. However, Yossepowitch et al. found dismal outcomes in four patients with total exenteration; two of them died soon after surgery, and another patient had a Grade IV complication. In light of the balance between tumor clearance and surgical burden, Sato et al. suggested that dialysis patients could be treated with a similar strategy to that for the general population with urothelial carcinoma. Nephroureterectomy was performed only with evidence of cancer involvement because our policy priority was to avoid subjecting patients to unnecessary surgical harm.
The overall 5-year bladder cancer survival rate following RC was approximately 60%,,, which was consistent with our study's findings. In dialysis patients, Tseng et al. reported a 5-year survival rate of 35.6% in patients with bladder cancer, and Kang et al. reported a 5-year survival rate of 42.9% in patients with upper urinary tract urothelial carcinoma after nephroureterectomy. In contrast to much of the literature that reported the outcomes of dialysis patients with urothelial carcinoma only, our study also included nondialysis patients with the same background as our control group. We found an acceptable overall 5-year survival rate for dialysis patients compared with nondialysis patients. In addition, the recurrence-free survival rates were similar in both groups. Close survival rates were also detected between the dialysis and nondialysis groups. In the multivariable analysis, muscle-invasive disease was identified as an independent factor affecting overall survival, although dialysis was not.
Even though dialysis patients generally had a lower survival expectancy, they displayed a higher rate (64%) of nonmuscle-invasive disease in our study. A high nonmuscle-invasive disease ratio (71%) in dialysis patients has also been reported in Taiwan by Tseng et al. Such a distribution might be due to the early alertness for hematuria in dialysis patients and the greater access to medical services for regular dialysis.
Metabolic diseases, such as diabetes mellitus and hypertension, accounted for approximately 50% of the causes of dialysis, followed by chronic glomerulonephritis (25.1%) and chronic interstitial nephritis (2.8%). To our knowledge, the common risk between dialysis and bladder cancer patients remains unclear. Nevertheless, the nephrotoxin aristolochic acid eventually induces interstitial nephritis and end-stage renal disease, which is also a carcinogen in the bladder. Although Chinese herbs containing aristolochic acid, such as Mu Tong and Fang Ji, have been banned in Taiwan since 2003, there were still victims. Xiong et al. reported a lower tumor stage (T2 or less than T2) in patients exposed to aristolochic acid with upper urinary tract urothelial carcinoma. This finding might also be applicable to bladder cancer, although further evidence is necessary.
Since advanced urothelial cancer cases with RC surgery are relatively rare due to poor quality of life and alternative treatment choices, this study included a small number of cases. The study excluded the analysis of long-term complications because of the small sample size and because most events occurred within 3 months, as well as the short follow-up time for evaluating the long-term outcome. Therefore, this study aimed to present a clinical observation rather than achieving strong statistical power. A further well-controlled large cohort study is necessary to confirm the findings.
Although dialysis typically leads to poor outcomes, a lower early complication rate and an acceptable survival outcome were observed in patients who underwent RC. These preliminary results could be used to reassure dialysis patients with bladder cancer of the safety and benefits of RC.
| Conclusion|| |
The results confirmed that dialysis patients who undergo RC may achieve acceptable survival outcomes and a relatively lower rate of early complications, especially urinary tract infection and bowel kinetic change, relatively short hospital stays, and relatively low readmission rates. Muscle-invasive disease was an independent factor for overall survival, although dialysis was not. Thus, we suggest that dialysis patients may safely benefit from undergoing RC.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
| References|| |
Chang SS, Bochner BH, Chou R, Dreicer R, Kamat AM, Lerner SP, et al
. Treatment of non-metastatic muscle-invasive bladder cancer: AUA/ASCO/ASTRO/SUO guideline. J Urol 2017;198:552-9.
Prcic A, Aganovic D, Hadziosmanovic O. Impact of complications and bladder cancer stage on quality of life in patients with different types of urinary diversions. Med Arch 2013;67:418-22.
Lee RK, Abol-Enein H, Artibani W, Bochner B, Dalbagni G, Daneshmand S, et al
. Urinary diversion after radical cystectomy for bladder cancer: Options, patient selection, and outcomes. BJU Int 2014;113:11-23.
Anderson CB, McKiernan JM. Surgical complications of urinary diversion. Urol Clin North Am 2018;45:79-90.
Lin MY, Kuo MC, Hung CC, Wu WJ, Chen LT, Yu ML, et al
. Association of dialysis with the risks of cancers. PLoS One 2015;10:e0122856.
Butler AM, Olshan AF, Kshirsagar AV, Edwards JK, Nielsen ME, Wheeler SB, et al
. Cancer incidence among US Medicare ESRD patients receiving hemodialysis, 1996-2009. Am J Kidney Dis 2015;65:763-72.
Syed-Ahmed M, Narayanan M. Immune dysfunction and risk of infection in chronic kidney disease. Adv Chronic Kidney Dis 2019;26:8-15.
Kanda H, Hirasaki Y, Iida T, Kanao-Kanda M, Toyama Y, Chiba T, et al
. Perioperative management of patients with end-stage renal disease. J Cardiothorac Vasc Anesth 2017;31:2251-67.
Pazeto CL, Baccaglini W, Tourinho-Barbosa RR, Glina S, Cathelineau X, Sanchez-Salas R. HRQOL related to UD in radical cystectomy: A systematic review of recent literature. Int Braz J Urol 2019;45:1094-104.
Wu CF, Chang PL, Chen CS, Chuang CK, Weng HH, Pang ST. The outcome of patients on dialysis with upper urinary tract transitional cell carcinoma. J Urol 2006;176:477-81.
Kang CH, Chen CH, Chiang PH. Primary urothelial carcinoma of the upper urinary tract in dialysis patients with 5-year follow-up. Jpn J Clin Oncol 2010;40:241-6.
Tseng SF, Chuang YC, Yang WC. Long-term outcome of radical cystectomy in ESDR patients with bladder urothelial carcinoma. Int Urol Nephrol 2011;43:1067-71.
Yossepowitch O, Sagy I, Margel D, Baniel J. Urothelial carcinoma of the bladder in patients on hemodialysis: Clinical characteristics and oncological outcomes. J Urol 2012;187:1215-9.
Sato Y, Kondo T, Takagi T, Junpei I, Tanabe K. Treatment strategy for bladder cancer in patients on hemodialysis: A clinical review of 28 cases. Int Urol Nephrol 2016;48:503-9.
Stein JP, Lieskovsky G, Cote R, Groshen S, Feng AC, Boyd S, et al
. Radical cystectomy in the treatment of invasive bladder cancer: Long-term results in 1,054 patients. J Clin Oncol 2001;19:666-75.
Sun M, Abdollah F, Bianchi M, Trinh QD, Shariat SF, Jeldres C, et al
. Conditional survival of patients with urothelial carcinoma of the urinary bladder treated with radical cystectomy. Eur J Cancer 2012;48:1503-11.
Gandaglia G, Sun M. Bladder cancer: Conditional survival after radical cystectomy. Nat Rev Urol 2014;11:8-9.
Hwang SJ, Tsai JC, Chen HC. Epidemiology, impact and preventive care of chronic kidney disease in Taiwan. Nephrology (Carlton) 2010;15 Suppl 2:3-9.
Chien CC, Han MM, Chiu YH, Wang JJ, Chu CC, Hung CY, et al
. Epidemiology of cancer in end-stage renal disease dialysis patients: A national cohort study in Taiwan. J Cancer 2017;8:9-18.
Xiong G, Yao L, Hong P, Yang L, Ci W, Liu L, et al
. Aristolochic acid containing herbs induce gender-related oncological differences in upper tract urothelial carcinoma patients. Cancer Manag Res 2018;10:6627-39.
[Table 1], [Table 2], [Table 3], [Table 4]