Vol 16 No 02 March-April 2019 145 UROLOGICAL ONCOLOGY Long-term Changes in Renal Function, Blood Electrolyte Levels, and Nutritional Indices After Radical Cystectomy and Ileal Conduit in Patients with Bladder Cancer Makito Miyake1*, Takuya Owari1, Mitsuru Tomizawa1, Masaru Matsui2, Naoko Nishibayashi3, Kota Iida1, Kenta Onishi1, Shunta Hori1, Yosuke Morizawa1, Daisuke Gotoh1, Yoshitaka Itami1, Yasushi Nakai1, Takeshi Inoue1, Satoshi Anai1, Kazumasa Torimoto1, Katsuya Aoki1, Nobumichi Tanaka1, and Kiyohide Fujimoto1 Purpose: To assess the long-term changes in renal function, blood electrolyte levels, and nutritional indices after radical cystectomy and ileal conduit in patients with bladder cancer. Patients and Methods: In 129 patients who underwent radical cystectomy and ileal conduit, we evaluated clinico- pathologic features, complications, and the change in the estimated glomerular filtration rate (eGFR) from baseline to 1, 2, 3, 4, 5, and 10 years postoperatively. Two nutritional indices, the geriatric nutritional risk index (GNRI) and prognostic nutrition index (PNI), were calculated with laboratory tests. Results: In the ileal conduit group, a parastromal hernia was observed in 10% of patients, whereas 13% had an ureteroenteric anastomotic stricture, which was associated with greater decline in the eGFR postoperatively. The first 5 year-decline in the eGFR was 1.74 mL/min/1.73 m2/year. The levels of only potassium showed a significant increase at 1 year postoperatively (mean: 4.34 mEq/L) and remained high compared with the baseline (4.14 mEq/L). Evaluation of the nutritional indices demonstrated that the GNRI, and not PNI, showed a significant, transient increase from 1 to 4 years (range: 108−110) postoperatively compared with the baseline (105). Conclusion: The first 5 year-decline was much higher than that among Japanese individuals who participated in an annual health examination program. Further research should be performed to identify an appropriate strategy for selecting the suitable type of urinary diversion and postoperative nutritional interventions to improve the clinical outcome of patients with bladder cancer. Keywords: Urinary Bladder Neoplasms; Cystectomy; Urinary Diversion; Kidney Failure, Chronic; Electrolyte, Nutritional Status INTRODUCTION Radical cystectomy (RC), with or without peri-operative, systemic chemotherapy, is the stand- ard treatment for selected patients with high-risk, non-muscle invasive bladder cancer (stage Tis or Ta/1) and muscle-invasive uroethelial cancer of the bladder (stage ≥T2)(1,2). RC requires reconstruction of the lower urinary tract, which is called urinary diversion (UD). Although ureterosigmoidostomy was the first widely selected UD, decrease of renal function with time, met- abolic acidosis, and the risk of secondary bowel adeno- carcinoma were significant disadvantages of this type of surgery and limited its clinical usefulness(3). Subse- quent advances in technology have provided several reconstructive options and substantial improvements in terms of both functional outcomes and health-related quality of life. Among the currently available options for UD after RC, ileal conduit is considered the “gold standard” for those with incontinent UD and has remained the major choice for patients with contraindications to continent UD. The latest version of European Association of Urology 1 Department of Urology, Nara Medical University, 840 Shijo-cho, Kashihara-shi, Nara 634-8522, Japan. 2 First Department of Internal Medicine, Nara Medical University, 840 Shijo-cho, Kashihara-shi, Nara 634-8522, Japan. 3 Department of Wound Ostomy Continence Nursing, Nara Medical University, 840 Shijo-cho, Kashihara-shi, Nara 634-8522, Japan. *Correspondence: Department of Urology, Nara Medical University, 840 Shijo-cho, Nara 634-8522, Japan. Tel: +81-744-22-3051 (ext 2338). Fax: +81-744-22-9282. E-mail: makitomiyake@yahoo.co.jp Received April 2018 & Accepted September 2018 guideline recommends offering an orthotopic bladder substitute or ileal conduit diversion to male and female patients lacking any contraindications and who have no tumour in the urethra or at the level of urethral dissec- tion(4). Ileal conduits are relatively easy and quick to construct, leading to a minimized rate of postoperative complications(5,6). However, RC and accompanying UD are associated with high risks of perioperative and long- term morbidity and mortality, including subsequent de- cline in renal function (7,8). For many years, one of the goals of UD was to protect renal function and restore anatomy, because a high proportion of bladder cancer patients present with impaired renal function(9). Although several reports have described deterioration of renal function over time after ileal conduit(10-13), defi- nite conclusions could not be made because of varia- tions in surgical skill and patient backgrounds. There is only limited information regarding long-term com- plications and changes in blood electrolyte levels and nutritional indices after ileal conduit. In this study, we explored the incidence of complications and post-surgi- cal, chronological changes in blood examination results Urological Oncology 146 in patients with ileal conduits and investigated the risk factors of the development of this condition. PATIENTS AND METHODS Data collection and follow-up The ethics committee of the Nara Medical University approved this study, and all participants provided in- formed consent (reference ID: 1256). The study was conducted in compliance with the study’s protocol and in accordance with the provisions of the Declaration of Helsinki (2013). The medical charts of 182 patients who underwent cu- rative RC between 2000 and 2017 were retrospectively reviewed. Eight patients were excluded because they underwent hemodialysis and did not require any UD procedure, and 14 patients were excluded because they had insufficient follow-up data, leaving 160 (88%) pa- tients for inclusion in this study. Of these, 129 (81%), 23 (14%), and 8 (5%) patients underwent ileal conduit, cutaneous ureterostomy, and ileal orthotopic neoblad- der, respectively (Figure 1). UD procedure was select- ed at a physician's discretion. Follow-up was performed according to our institutional protocol(1). Laboratory data, including the serum creatinine, albumin, blood lymphocyte, and blood electrolyte (sodium, potassi- um, chloride, and calcium) levels, were measured at baseline and follow-up visits at regular intervals af- ter RC and were obtained from the patients’ medical charts. The estimated glomerular filtration rate (eGFR) Long-term changes after radical cystectomy and ileal Conduit-Miyake et al. Variables Total cases Type of UD P value IC CU NB 3 group comparison† 2 group comparison‡ 2 group comparison‡ IC vs CU IC vs NB No. of cases 160 (100%) 129 (81%) 23 (14%) 8 (5%) - - - Sex Male 127 (79%) 103 (80%) 18 (78%) 7 (88%) 0.84 0.78 0.99 Female 33 (21%) 22 (20%) 5 (22%) 1 (12%) ECOG-PS 0 134 (84%) 111 (86%) 20 (87%) 7 (88%) 0.97 0.99 0.99 1—3 26 (16%) 18 (14%) 3 (13%) 1 (12%) Charlson 0 133 (83%) 108 (83%) 17 (74%) 8 (100%) 0.22 0.25 0.61 Comorbidity Index 1—3 27 (17%) 21 (17%) 6 (26%) 0 (0%) Clinical T T1/Tis 9 (6%) 7 (5%) 2 (9%) 0 (0%) 0.07 0.018 0.69 category T2 71 (44%) 55 (43%) 11 (48%) 5 (63%) T3 45 (28%) 41 (32%) 0 (0%) 2 (25%) T4 35 (22%) 26 (20%) 8 (35%) 1 (12%) Clinical N N0 146 (91%) 116 (90%) 22 (96%) 8 (100%) 0.44 0.69 0.99 category N ≥1 14 (9%) 13 (10%) 1 (4%) 0 (0%) Carcnoma Neagative 99 (62%) 82 (64%) 11 (48%) 6 (75%) 0.26 0.17 0.71 in situ Positive 61 (38%) 47 (36%) 12 (52%) 2 (25%) Neoadjuvant No 97 (61%) 71 (55%) 20 (87%) 6 (75%) 0.011 0.005 0.46 chemotherapy Yes 63 (39%) 58 (45%) 3 (13%) 2 (25%) Adjuvant No 134 (84%) 107 (83%) 20 (87%) 7 (88%) 0.85 0.77 0.99 chemotherapy Yes 26 (16%) 22 (17%) 3 (13%) 1 (12%) Age at RC (mean ± SD) 70.0 ± 8.7 69.8 ± 8.3 73.9 ± 10.1 63.3 ± 5.3 0.0013 0.049 0.037 BMI (mean ± SD) 22.5 ± 3.9 22.4 ± 3.7 23.3 ± 5.3 23.2 ± 2.7 0.67 0.99 0.99 (Kg/m2) Serum (mean ± SD) 1.09 ± 0.95 1.02 ± 0.88 1.55 ± 1.30 0.95 ± 0.36 0.025 0.022 0.99 Creatinine (mg/dL) Estmated GFR (mean ± SD) 62.0 ± 22.4 64.6 ± 21.9 46.5 ± 20.6 65.7 ± 18.4 0.0022 0.02 0.99 (mL/min/1.73m2) PNI (mean ± SD) 49.8 ± 5.4 49.8 ± 5.3 48.2 ± 5.4 54.8 ± 3.8 0.015 0.88 0.028 GNRI (mean ± SD) 95.3 ± 19.3 95.3 ± 19.9 100.1 ± 11.2 99.7 ± 28.6 0.15 0.99 0.16 Table 1. Characteristics of 160 patients undergoing radical cystectomy and comparison between urinary diversion. UD, urinary diversion; IC, Ileal conduit; CU, cutaneous ureterostomy; NB, ileal orthotopic neobladder; ECOG-PS, the Eastern Cooperative Oncology Group Per- formance Status; RC, radical cystectomy; BMI, body mass index; eGFR, estimated glomerular filtration rate; PNI, prognostic nutritional index; GNRI, geriatric nutritional risk index; SD, standard deviation; †, Kruskal-Wallis or Chi-squared test; ‡, post hoc Dunn's test or Fisher’s exact test Figure 1. Flow chart for creating the patient dataset. Vol 16 No 02 March-April 2019 147 was calculated using the Modification of Diet in Re- nal Disease Study formula for Japanese patients: eGFR mL/min/1.73 m2 = 194 × serum creatinine −1.094 × age−0.287 (× 0.739 for women) (14). The chronic kid- ney disease (CKD) stages were defined according to the eGFR (15). The Charlson comorbidity index, which was updated in 2011, was applied for evaluating pre- operative comorbidities (16). The stage was assigned ac- cording to the 2009 TNM classification of the Union of International Cancer Control. Calculation of nutrition-based markers The geriatric nutritional risk index (GNRI) and prog- nostic nutrition index (PNI) were calculated using lab- oratory data that were measured during the follow-up period (17). The GNRI score was calculated using the serum albumin levels and ratios of the actual body weight to ideal body weight, which was 22 × the square of height in meters. Thus, GNRI = 14.89 × the serum albumin concentration (g/dL) + 41.7 × (body weight in kg/ideal body weight). The PNI was calculated as 10 × the serum albumin level (g/dL) + 0.005 × the total lym- phocyte count (per mm3). Both indices were reported as continuous variables for the analyses. RC, lymphadenectomy and UD procedures Of the 129 patients with ileal conduit, 103 (80%) un- derwent open RC and 26 (20%) underwent laparoscopic RC. Lymphadenectomy procedures, including remov- al of the obturator, external iliac, common iliac, and parasacral lymph node chains, were performed basi- cally according to the extended template(18). Regarding the construction of ileal conduits, the terminal ileum was preserved to ensure that bile salts, vitamin B12, and fat-soluble vitamins were adequately maintained(5). A segment of the ileum of approximately 20 cm was isolated and used for UD. The ureters were split and anastomosed to the oral side separately in an open end- to-side manner. The ileal segment of the anal side was anastomosed to the abdominal wall in a nipple-to-sto- ma manner. Cutaneous ureterostomy was performed by two methods: one ureter was brought across the midline and the two ureters were placed side by side in a dou- ble-barrel fashion or the two distal ureteric ends were placed individually. The stoma for cutaneous ureteros- tomy was created according to the Toyoda method (19). In orthotopic ileal neobladder, ileal construction was performed according to Studer reservoir (20). Evaluation of postoperative complications Complications after RC were objectively evaluated ac- cording to the Clavien-Dindo classification system (21). Early and late complications were defined as complica- tions occurring within 90 days of RC and 90 days after RC, respectively. Parastomal hernia is defined as any protrusion in the vicinity of the urostoma with the pa- tient straining in a supine and an erect position(22). Statistical analyses The clinicopathological characteristics of the patients in this study were compared using the Kruskal-Wallis test, following the post hoc test (Dunn test), Chi-squared test, and Fisher’s exact test, as appropriate. Continuous variables are expressed in means ± standard deviations and shown in line charts. The normality was checked by Shapiro-Wilk test. The Student t-test, Mann-Whit- ney U test, paired t-test, or Wilcoxon’s signed-rank test was used, as appropriate. The cumulative rate of complications was drawn using the Kaplan-Meier plot. The linear regression analysis was used to calcurate the annual eGFR decrement. IBM SPSS version 21 (SPSS Inc., Chicago, IL, USA) and PRISM software version 7.00 (GraphPad Software, Inc., San Diego, CA, USA) were used for statistical analyses and data plotting, re- spectively. Statistical significance was set at P < 0.05, and all reported P-values were two-sided. In the paired t-test for long-term changes in continuous values, power analysis using G*Power (version 3.1.9.2) was performed a priori, and showed that a sample of 34 patients was required to detect a between-group differ- ence given an effect size of 0.50, a power of 0.80 and an alpha of 0.05. RESULTS Patient characteristics The clinicopathological characteristics of the 160 pa- tients undergoing RC and UD are listed in Table 1. The median follow-up period after RC was 44.1 months. During the follow-up period, 49 patients died (31%), including 35 with recurrent disease (22%). Other caus- es of death were acute myocardiac infarction in two patients, pneumonia in two, panperitonitis due to in- testinal perforation in two, other malignancy in two, chronic kidney disease in one, urinary tract infection in one, heart failure in one, and unknown in three, respec- tively. Sixty-nine patients (39%) received two to three cycles of platinum-based neoadjuvant chemotherapy and 26 patients (16%) received two to three cycles of platinum-based adjuvant chemotherapy. Almost half of the patients undergoing ileal conduit received neo- adjuvant chemotherapy, whereas only 13% of patients undergoing cutaneous ureterostomy received neoad- juvant chemotherapy (P = 0.005). Forty-one (32%) of the 129 patients undergoing ileal conduit had stage T3 Long-term changes after radical cystectomy and ileal Conduit-Miyake et al. Table 2. The early and late complications in 129 patients undergoing ileal conduit. Early or late Complications Total Clavien-Dindo calssification I / II IIIa IIIb IV Early (< 90 days) Bowel obstruction 32 (25%) 22 (17%) 8 (6%) 2 (2%) Surgical site infection 29 (22%) 13 (10%) 10 (8%) 5 (2%) 1 (1%) Pelvic abscess 19 (15%) 1 (1%) 10 (8%) 8 (6%) Ureteroenteric anastomotic stricture 9 (7%) 5 (4%) 4 (3%) Intestinal anastomotic leakage 7 (5%) 7 (5%) Ureteroenteric anastomotic leakage 3 (2%) 1 (1%) 2 (2%) Late (> 90 days) Parastomal hernia 13 (10%) 12 (9%) 1 (1%) Ureteroenteric anastomotic stricture 8 (6%) 2 (2%) 6 (5%) Abdominal incisional hernia 8 (6%) 5 (4%) 3 (2%) Stomal stenosis 3 (2%) 1 (1%) 2 (2%) Urological Oncology 148 disease, whereas no patients with stage T3 disease un- derwent cutaneous ureterostomy (P = 0.018). Patients undergoing ileal conduit were younger than those who underwent cutaneous ureterostomy, but older than those who underwent orthotopic neobladder. The eGFR in patients with cutaneous ureterostomy was lower than that in those with ileal conduit (P = 0.02). However, sex, performance status, the Charlson comorbidity in- dex, clinical N category, presence of carcinoma in situ, and adjuvant chemotherapy were not associated with the selected type of UD. Early and late complications Both early and late complications were observed after RC and ileal conduit. The incidence of complications, expressed as numbers and percentages, is summarized in Table 2. The most frequent complication was bowel obstruction (32 patients, 25%), which sometimes re- quired an indwelling ileus tube or surgical intervention, such as synectenterotomy. Ureteroenteric anastomotic stricture, ureteroenteric anastomotic leakage, paras- tomal hernia, and stomal stenosis were complications that were specific to ileal conduit. Among 17 patients presenting with an ureteroenteric stricture, bilateral strictures were observed in 5, while the remaining 12 had a unilateral stricture. Regarding stoma-related, late complications during the follow-up period, parastromal hernia was observed in 13 patients, one of whom un- derwent repair surgery using mesh. Among the patients presenting with complications, the median time from ileal conduit to the diagnosis of ureteroenteric stricture and parastomal hernia was 29 and 11 months, respec- tively (Figure 2). Three patients (2%) had stomal steno- sis; however, none had prolapse of the stoma. Baseline and postoperative change in renal function The baseline eGFR of the 129 patients undergoing ileal conduit was 64.6 ± 21.9 mL/min/1.73 m2. The CKD stage was G1 in 9 (7%), G2 in 54 (42%), G3a in 34 (26%), G3b in 14 (11%), and G4 in 5 (4%) patients. The detailed 5-year follow-up data of 45 (35%) of these 129 patients were available and subjected to the analy- ses of the change in renal function over time. In these 45 patients, the CKD stage was G1 in 4 (9%), G2 in 19 (42%), G3a in 15 (33%), G3b in 6 (13%), and G4 in 1 (2%) patient, and this distribution was not statistical- ly different from that of the remaining 84 of patients (P=0.81). The change in the eGFR after surgery was plotted on line graphs (Figure 3A). The mean eGFR was 72.6 at baseline, 71.9 at 1 year, 69.3 at 2 years, 66.7 at 3 years, 64.6 at 4 years, 63.9 at 5 years, and 62.1 at 10 years postoperatively. The first 5-year decrease in the eGFR was 8.7, and the next 5-year decrease was 2.2. During the first 5 years postoperatively, the eGFR de- crease rate was 1.74 per year. From 5 to 10 years post- operatively, the eGFR decrease rate was only 0.55 per year. During the first 5 years following ileal conduit, the eGFR decline rate was 1.74 per year (Figure 3A). Along with the creatinine level and eGFR, the blood urea nitrogen (BUN) level was used to evaluate renal function and help diagnose renal disease. The BUN lev- el significantly increased until 1 year postoperatively and did not continue to rise, and was not concordant with our observation of the eGFR (Figure 3B). The postoperative decrease rate of the eGFR was compared between patients with an ureteroenteric stricture and those without (Figure 3C). Patients with an ureteroen- teric stricture had slightly higher decrease in the eGFR than did those without, although there was no signifi- cant difference. A similar analysis showed that periop- erative chemotherapy (neoadjuvant or adjuvant) did not affect the decrease rate of the eGFR after ileal conduit (Figure 3D). The CKD stage of the 45 selected patients at baseline, 3 years, and 5 years is shown in Figure 3E. The number of patients with stage G1/G2 decreased, whereas that of patients with stage G3/G4 increased over time. Hemo- dialysis was required for two patients (4%) (CKD stage 5D) during the follow-up period. One of these patients was 53-year-old woman with an eGFR of 23.8 at the baseline examination and the second was 78-year-old man with an eGFR of 42.4 at baseline. Postoperative changes in blood electrolyte levels and nutritional indices The change in blood electrolyte levels and nutritional indices from baseline to 10 years after ileal conduit was plotted on line graphs (Figures 4A-F). Among the four blood electrolytes that were tested, only potassium showed a significant increase at 1 year postoperatively, and its level remained high compared to that at baseline (Figure 4B). An evaluation of the nutritional indices demonstrated that the GNRI showed a significant, tran- sient increase from 1 to 4 years postoperatively (Fig- ures 4F, G). In contrast, the PNI did not change post- operatively (Figure 4H). DISCUSSION In this single-center study, we reported the postoper- ative complications and changes over time in various laboratory examination results after RC and ileal con- Long-term changes after radical cystectomy and ileal Conduit-Miyake et al. Figure 2. Kaplan-Meier plots for calculating the cumulative inci- dence of complications. (A) ureteroenteric stricture and (B) paras- tomal hernia. The numbers at risk are shown. Vol 16 No 02 March-April 2019 149 duit. Invasive bladder cancer has aggressive features and requires intensive interventions, such as RC and UD. To improve a patient’s quality of life, long-term management of complications and changes after sur- gery has become essential. Substantial variability exists in the incidence of early and late complications after UD (3,7,8). The types and rates of complications depend on the selected UD, and these complications can be classified roughly into three types: bowel anastomosis-related, reservoir/conduit-re- lated, and ureteroenteric anastomosis-related (23). In the present study, we focused on two postoperative compli- cations: parastomal hernia and ureteroenteric stricture. A parastomal hernia occurs when the edges of the sto- ma come away from the muscle, allowing abdominal contents such as a section of the bowel or omentum to come out(22). Shimko et al. performed a large study of 1,057 patients with a median follow-up of 9.2 years and observed parastomal hernias in 14% of the patients (8), which was similar to the result of our cohort (10%). A symptomatic parastomal hernia leads to poor quality of life. While the hernias of most patients can be managed conservatively with stomal support, including an ab- dominal support belt, surgical intervention is required if there is incarceration or strangulation of the hernia, or other complications. Because many patients with muscle-invasive uroetheli- al cancer of the bladder have baseline renal impairment to some degree (partially owing to high age)(9,24), pro- tecting renal function and the upper urinary tract after UD is one of the main clinical concerns. According to previous reports, more than half of the patients under- going RC and UD experienced deterioration of renal function, regardless of the type of UD (13,25). Several risk factors, such as hypertension, diabetes mellitus, high age, baseline eGFR, postoperative acute pyelonephri- tis, and the type of UD, contribute to a decrease in the postoperative eGFR(10-13). We demonstrated that a uret- eroenteric stricture could be associated with a decrease in the postoperative eGFR, although it did not reach sta- tistical significance. Eisenberg et al. revealed that there was an association between ureteroenteric strictures and a decrease of more than 10 ml/min/1.73 m2 in the eGFR in a multivariate analysis of 1,241 patients under- going ileal conduit. According to a survey of the decline in renal function over 10 years in 120,727 participants aged 40 years or older, the average rate of eGFR decline was 0.36 per year (26). During the first 5 years following ileal conduit, the eGFR decline rate was 1.74 per year (Figure 3A), which was much higher than that of indi- viduals who participated in an annual health examina- tion program in Japan (0.36 per year). Long-term changes after radical cystectomy and ileal Conduit-Miyake et al. Figure 3. Change over time in the renal function after radical cys- tectomy and ileal conduit. A and B: The change over time in the eGFR and BUN was shown and plotted with means ± standard deviations. Values at each postoperative time point (1, 2, 3, 4, 5, and 10 years) were compared with values at baseline using the paired t-test or Wilcoxon’s signed-rank test as appropriate. n.s.: not significant; *: P < 0.05; **: P < 0.01; and ***: P < 0.001. The data from 21 patients are available for 10-year study. C and D: Comparison of changes in the eGFR postoperatively according to ureteroenteric strictures and perioperative platinum-based chemo- therapy. The data of patients with an ureteroenteric stricture (red) and those without (blue) were compared at each time point using the Mann-Whitney U-test. n.s.: not significant (B). The data of pa- tients who received perioperative platinum-based chemotherapy (red) and those who did not (blue) were compared as well (C). D: The distribution of patients according to the CKD stage is shown as a bar plot for the baseline, 3-year postoperative, and 5-year post- operative values. eGFR: estimated glomerular filtration rate; BUN: blood urea nitrogen; CKD: chronic kidney disease Figure 4. Time course of change in the blood electrolytes and nu- trition index after radical and ileal conduit Urological Oncology 150 A previous study reports metabolic acidosis rates of 14.8% at 1 month and 10.0% at 1 year after ileal con- duit(27). A significant association between renal func- tion and the development of metabolic acidosis was observed, and it was especially strong in the early postoperative period. The majority of patients present with clinically insignificant acidosis, but in some cases, acidosis can provoke bone demineralization and other complications. Bowel segment maintains its absorptive function and enables many substances such as urine, ammonia, hydrogen, and chloride to be reabsorbed into the blood flow. This results in metabolic, hyper- chloremic acidosis and an increased load of nitrogen compounds, especially when the colonic part is used for UD. Acid-base imbalance is usually treated with sodi- um citrate, sodium bicarbonate, nicotinic acid, or chlo- ropromazine(28). Electrolyte disorders are more common in patients undergoing continent UD than in those with incontinent UD. When the ileum is used for UD, hy- pokalemia with coexisting acidosis is typical and prob- lematic(29). Among our cohort, no patients experienced clinically symptomatic acidemia, hyperchloremic aci- dosis, hypokalemia, or hypocalcemia. We previously reported that the PNI value showed tran- sient deterioration at 1 and 3 months after RC, with a return to baseline values at 6 months(30). In the current study, we evaluated long-term postoperative changes in two nutritional indices. Although the PNI did not show any postoperative change, the GNRI value showed a significant, transient increase from 1 to 4 years post- operatively. The PNI was invented to predict the risk of complications after gastrointestinal surgery, and the GNRI was established to predict the risk of morbidi- ty and mortality in hospitalized elderly patients. Few studies have addressed the nutritional status of patients undergoing RC and UD. The accuracy and utility of es- tablished nutritional indices such as the PNI, GNRI, and controlling nutritional status index should be confirmed using a larger cohort of patients. The present study has several limitations. The first is its retrospective nature, with a potential selection bias; for example, some patients were excluded because their data were insufficient. There were missing data regard- ing the comorbidities including diabetic mellitus and hypertension, which could be potential risk factors for the decline in renal function. Third, this study includes only 45 patients in the subanalysis, which is considered to be a relatively low sample size. CONCLUSIONS We explored the long-term complications and change in renal function, blood electrolyte levels, and nutri- tional indices after RC and ileal conduit. Further studies should be performed to identify an appropriate strategy for selecting a suitable type of UD and postoperative nutritional interventions to improve the clinical out- come of surgery in these patients. REFERENCES 1. Miyake M, Morizawa Y, Hori S, et al. Integrative Assessment of Pretreatment Inflammation-, Nutrition-, and Muscle-Based Prognostic Markers in Patients with Muscle- Invasive Bladder Cancer Undergoing Radical Cystectomy. Oncology 2017; 93: 259-69. Long-term changes after radical cystectomy and ileal Conduit-Miyake et al. REFERENCES 1. Miyake M, Morizawa Y, Hori S, et al. Integrative Assessment of Pretreatment Inflammation-, Nutrition-, and Muscle-Based Prognostic Markers in Patients with Muscle-Invasive Bladder Cancer Undergoing Radical Cystectomy. Oncology 2017; 93: 259-69. 2. Üçer O, Albaz AC, Atag E, et al. The Rate of Neoadjuvant Chemotherapy Use in Muscle Invasive Bladder Cancer and The Approach of Urologists in Turkey. Urol J. 2016; 13: 2841- 4. 3. 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. 4. Alfred Witjes J, Lebret T, Compérat EM, et al. Updated 2016 EAU Guidelines on Muscle- invasive and Metastatic Bladder Cancer. Eur Urol 2017; 71: 462-75. 5. Bricker EM. Bladder substitution after pelvic evisceration. Surg Clin North Am 1950; 30: 1511-21. 6. Cordonnier JJ, Nicolai CH. An evaluation of the use of an isolated segment of ileum as a means of urinary diversion. J Urol 1960; 83: 834-8. 7. Shabsigh A, Korets R, Vora KC, et al. Defining early morbidity of radical cystectomy for patients with bladder cancer using a standardized reporting methodology. Eur Urol 2009; 55: 164-74. 8. Shimko MS, Tollefson MK, Umbreit EC, Farmer SA, Blute ML, Frank I. Long-term complications of conduit urinary diversion. J Urol 2011; 185: 562-7. 9. Canter D, Viterbo R, Kutikov A, et al. Baseline renal function status limits patient eligibility to receive perioperative chemotherapy for invasive bladder cancer and is minimally affected by radical cystectomy. Urology 2011; 77: 160–5. 10. Nishikawa M, Miyake H, Yamashita M, Inoue TA, Fujisawa M. Long-term changes in renal function outcomes following radical cystectomy and urinary diversion. Int J Clin Oncol 2014; 19: 1105-11. 11. Eisenberg MS, Thompson RH, Frank I, et al. Long-term renal function outcomes after radical cystectomy. J Urol 2014; 191: 619-25. 12. Osawa T, Shinohara N, Maruyama S, et al. Long-term renal function outcomes in bladder cancer after radical cystectomy. Urol J 2013; 10:784-9. 13. Hatakeyama S, Koie T, Narita T, et al. Renal Function Outcomes and Risk Factors for Stage 3B Chronic Kidney Disease after Urinary Diversion in Patients with Muscle Invasive Bladder Cancer. PLoS One 2016; 11: e0149544. Vol 16 No 02 March-April 2019 151 2. Üçer O, Albaz AC, Atag E, et al. The Rate of Neoadjuvant Chemotherapy Use in Muscle Invasive Bladder Cancer and The Approach of Urologists in Turkey. Urol J. 2016; 13: 2841- 4. 3. 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. 4. Alfred Witjes J, Lebret T, Compérat EM, et al. Updated 2016 EAU Guidelines on Muscle- invasive and Metastatic Bladder Cancer. Eur Urol 2017; 71: 462-75. 5. Bricker EM. Bladder substitution after pelvic evisceration. Surg Clin North Am 1950; 30: 1511-21. 6. Cordonnier JJ, Nicolai CH. An evaluation of the use of an isolated segment of ileum as a means of urinary diversion. J Urol 1960; 83: 834-8. 7. Shabsigh A, Korets R, Vora KC, et al. Defining early morbidity of radical cystectomy for patients with bladder cancer using a standardized reporting methodology. Eur Urol 2009; 55: 164-74. 8. Shimko MS, Tollefson MK, Umbreit EC, Farmer SA, Blute ML, Frank I. Long-term complications of conduit urinary diversion. J Urol 2011; 185: 562-7. 9. Canter D, Viterbo R, Kutikov A, et al. Baseline renal function status limits patient eligibility to receive perioperative chemotherapy for invasive bladder cancer and is minimally affected by radical cystectomy. Urology 2011; 77: 160–5. 10. Nishikawa M, Miyake H, Yamashita M, Inoue TA, Fujisawa M. Long-term changes in renal function outcomes following radical cystectomy and urinary diversion. Int J Clin Oncol 2014; 19: 1105-11. 11. Eisenberg MS, Thompson RH, Frank I, et al. Long-term renal function outcomes after radical cystectomy. J Urol 2014; 191: 619-25. 12. Osawa T, Shinohara N, Maruyama S, et al. Long-term renal function outcomes in bladder cancer after radical cystectomy. Urol J 2013; 10:784-9. 13. Hatakeyama S, Koie T, Narita T, et al. Renal Function Outcomes and Risk Factors for Stage 3B Chronic Kidney Disease after 14. Matsuo S, Imai E, Horio M, et al. Revised equations for estimated GFR from serum creatinine in Japan. Am J Kidney Dis 2009; 53: 982–92. 15. Levey AS, de Jong PE, Coresh J, et al. The definition, classification, and prognosis of chronic kidney disease: a KDIGO Controversies Conference report. Kidney int 2011; 80: 17–28. 16. Quan H, Li B, Couris CM, et al. Updating and validating the Charlson comorbidity index and score for risk adjustment in hospital discharge abstracts using data from 6 countries. Am J Epidemiol 2011; 173: 676-82. 17. Narumi T, Arimoto T, Funayama A, et al. Prognostic importance of objective nutritional indexes in patients with chronic heart failure. J Cardiol 2013; 62: 307-13. 18. Sundi D, Svatek RS, Nielsen ME, Schoenberg MP, Bivalacqua TJ. Extent of pelvic lymph node dissection during radical cystectomy: is bigger better? Rev Urol. 2014; 16: 159-66. 19. Toyoda Y. A new technique for catheterless cutaneous ureterostomy. J Urology. 1977; 117:276–8. 20. Studer UE, Turner WH. The ileal orthotopic bladder. Urology. 1995; 45:185-9. 21. Dindo D, Demartines N, Clavien PA. Classification of surgical complications: a new proposal with evaluation in a cohort of 6336 patients and results of a survey. Ann Surg 2004; 240: 205-13. 22. Jänes A, Weisby L, Israelsson LA. Parastomal hernia: clinical and radiological definitions. Hernia. 2011; 15: 189-92. 23. Farnham SB, Cookson MS. Surgical complications of urinary diversion. World J Urol 2004; 22: 157–67. 24. Imai E, Horio M, Watanabe T, et al. Prevalence of chronic kidney disease in the Japanese general population. Clinical and experimental nephrology 2009; 13: 621–30. 25. Gershman B, Eisenberg MS, Thompson RH, et al. Comparative impact of continent and incontinent urinary diversion on long-term renal function after radical cystectomy in patients with preoperative chronic kidney disease 2 and chronic kidney disease 3a. Int J Urol 2015; 22: 651–6. 26. Imai E, Horio M, Yamagata K, et al. Slower decline of glomerular filtration rate in the Japanese general population: a longitudinal 10-year follow-up study. Hypertens Res 2008; 31: 433-41. 27. Krajewski W, Piszczek R, Krajewska M, Dembowski J, Zdrojowy R. Urinary diversion metabolic complications - underestimated problem. Adv Clin Exp Med 2014; 23: 633-8. 28. Van der Aa F, Joniau S, Van Den Branden M, Van Poppel H. Metabolic changes after urinary diversion. Adv Urol 2011; 2011: 764325. 29. Tanrikut C, McDougal WS. Acid-base and electrolyte disorders after urinary diversion. World J Urol 2004; 22: 168-71. 30. Miyake M, Morizawa Y, Hori S, et al. Clinical impact of postoperative loss in psoas major muscle and nutrition index after radical cystectomy for patients with urothelial carcinoma of the bladder. BMC Cancer 2017; 17: 237. Long-term changes after radical cystectomy and ileal Conduit-Miyake et al.