Bowel Function Remains Subjectively Unchanged After Ileal Resection for Construction of Continent Ileal Reservoirs

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1 EUROPEAN UROLOGY 60 (2011) available at journal homepage: Reconstructive Urology Bowel Function Remains Subjectively Unchanged After Ileal Resection for Construction of Continent Ileal Reservoirs Berry Fung, Thomas M. Kessler, Katharina Haeni, Fiona C. Burkhard, Urs E. Studer * Department of Urology, University of Bern, Bern, Switzerland Article info Article history: Accepted May 23, 2011 Published online ahead of print on June 1, 2011 Keywords: Radical cystectomy Bladder substitution Bowel function Quality of life Questionnaire Abstract Background: Construction of a continent catheterizable urinary reservoir or an orthotopic bladder substitute requires substantial bowel resection, which can cause changes in bowel transit time. The reported incidence of chronic diarrhea after ileocecal resection is about 20%. Studies assessing bowel function after resection of cm of ileum without compromising the ileocecal valve are scarce, and long-term results have not been reported. Objective: Prospective assessment of possible changes in bowel function (eg, stool frequency, diarrhea) and the potential impact on quality of life in patients with resection of small bowel for urinary diversion. Design, setting, and participants: A total of 82 patients who underwent radical cystectomy, extended lymph node dissection, orthotopic ileal bladder substitution, or heterotopic continent cutaneous urinary diversion with a follow-up >1 yr after surgery were prospectively evaluated. Patients who had a neurogenic bladder disorder, had undergone previous radiotherapy, or had not completed the questionnaire were excluded from the study. The validated Gastrointestinal Quality of Life Index was completed by the patients preoperatively and at 3, 12, and 24 mo postoperatively. Five points concerning bowel function (frequent bowel movement, urgent bowel movement, diarrhea, constipation, or uncontrolled stool loss) were assessed, and the median scores were compared pre- and postoperatively. Results and limitations: Most patients (80%) were rarely or never troubled by frequent or urgent bowel movements, diarrhea, constipation, or uncontrolled stool loss preoperatively. In the case of stool frequency, a remarkable shift from rarely to never was observed postoperatively at 3, 12, and 24 mo. Scores for constipation and uncontrolled stool loss remained unchanged throughout the whole time period. For urgent bowel movements the median preoperative score of 4 decreased to 3 at 3 mo and 12 mo and returned to 4 at 24 mo. For diarrhea the preoperative score of 4 decreased to 3 at 3 mo and 24 mo and remained at 4 after 12 mo. Conclusions: No relevant changes in bowel movements were found after resection of cm of ileum if the terminal ileum and the ileocecal valve were left intact. # 2011 European Association of Urology. Published by Elsevier B.V. All rights reserved. * Corresponding author. Department of Urology, University of Bern, 3010 Bern, Switzerland. Tel ; Fax: address: urs.studer@insel.ch (U.E. Studer) /$ see back matter # 2011 European Association of Urology. Published by Elsevier B.V. All rights reserved. doi: /j.eururo

2 586 EUROPEAN UROLOGY 60 (2011) Introduction Construction of a continent urinary reservoir or an orthotopic bladder substitute requires resection of a substantial piece of small or large bowel. The risk of malabsorption, diarrhea, and metabolic problems related to reabsorption of urinary solutes depends on the type of bowel used [1 3]. Ileocecal valve resection for urinary diversion often results in bowel dysfunction [4 7], and chronic diarrhea occurs in up to 23% of patients [6]. Studies assessing stool frequency after resection of cm of ileum without compromising the ileocecal valve are scarce, and long-term results have not been reported. We therefore used a validated questionnaire to evaluate bowel function after resection of cm of small bowel while sparing the terminal ileum and ileocecal valve. 2. Patients and methods 2.1. Patients Patients who underwent cystectomy and bladder substitution for bladder cancer, who had a follow-up >1 yr after surgery and who volunteered to participate by completing a quality-of-life (QOL) questionnaire before and after surgery, were included in this prospective study. Patients who had a concomitant neurogenic bladder disorder, had undergone previous radiotherapy, or had not completed the questionnaire were excluded from the study. In all patients cm of the distal ileum were resected for either orthotopic ileal bladder substitution or heterotopic continent cutaneous urinary diversion using the same cross-folded ileal reservoir with an afferent tubular isoperistalticsegment [8]. The terminal25 cm ofileum and the ileocecal valve were spared. Intestinal continuity was restored by an end-to-end anastomosis of the bowel with a continuous seromuscular suture. Postoperatively, gastrointestinal function was stimulated by subcutaneous injections of parasympathomimetic drugs (0.5 mg neostigmine methylsulfate up to six times per day) beginning on postoperative day 2 and continuing until bowel activity resumed. Antiemetics were given on request. No patients received any antimotility agents Measurement and statistical analysis Gastrointestinal function was assessed using the validated Gastrointestinal Quality of Life Index (GIQLI) [9]. This questionnaire was part of a Table 1 The five questions from the Gastrointestinal Quality of Life Index concerning bowel habits Q1. How often during the past 2 weeks have you been troubled by stool frequency? Q2. How often during the past 2 weeks have you been troubled by urgent bowel movements? Q3. How often during the past 2 weeks have you been troubled by diarrhea? Q4. How often during the past 2 weeks have you been troubled by constipation? Q5. How often during the past 2 weeks have you been troubled by uncontrolled stool loss? broad-based QOL evaluation preoperatively and at 3, 12, and 24 mo postoperatively that also incorporated validated questionnaires regarding sexual and voiding function as well as general well-being. The five questions of the GIQLI applied in this study concern frequency of bowel movement, urgency of bowel movement, diarrhea, constipation, or uncontrolled stool loss (Table 1). The grading for each question was 0 all the time, 1 most of the time, 2 sometimes, 3 rarely, and 4 never. Data were not normally distributed and were presented as median and range. The Wilcoxon signed rank test was used to compare preoperative scores with scores 3, 12, and 24 mo postoperatively. A p value <0.05 was considered significant. Statistical analysis was performed using SPSS v.17.0 (SPSS Inc, Chicago, IL, USA). 3. Results A total of 136 orthotopic ileal bladder substitutions and 20 heterotopic continent urinary diversions were performed for bladder cancer from January 2004 to September Seventy-four patients were excluded, due to follow-up <1 yr (32) or incomplete or lacking response to the GIQLI preoperatively (23) and/or postoperatively (19), leaving 82 patients for data analysis. The median age of the 82 patients at the time of surgery (14 women, 68 men) was 63 yr (range: yr). Seventyeight underwent orthotopic ileal bladder substitution and four underwent heterotopic continent urinary diversion. A total of 37% of patients (30 of 82) had bilateral, 58% had unilateral (48 of 82), and 5% (4 of 82) had non nervesparing surgery. The median total length of ileum resected was 55 cm (range: cm), and the median ileum length used for construction of the reservoir was 39 cm (range: cm). The pathologic tumor stages were TIS in 1% (1 of 82), Ta in 5% (4 of 82), T1 in 29% (24 of 82), T2 in 39% (32 of 82), T3 in 22% (18 of 82), and T4 in 4% (3 of 82). A total of 23% of the patients (19 of 82) had lymph node metastasis. The median follow-up after surgery was 2.7 yr (range: yr). Preoperatively, almost 80% of the patients were rarely or never troubled by stool frequency, and similar results were reported at 3, 12, and 24 mo postoperatively (Fig. 1). Regarding problems caused by stool frequency, there was a remarkable shift from rarely preoperatively to never postoperatively. The median preoperative score was 3 and improved to a median of 4 at 3 mo ( p = 0.002), 12 mo ( p = 0.023), and 24 mo ( p = 0.59) postoperatively. About 90% of the patients were rarely or never troubled by urgent bowel movements preoperatively (Fig. 2). These percentages decreased slightly at 3, 12, and 24 mo postoperatively. The median preoperative score was 4 and decreased postoperatively to a median of 3 at 3 mo ( p = 0.031) and at 12 mo ( p = 0.058) but increased again to 4 at 24 mo ( p = 0.078). Preoperatively, >90% of the patients were rarely or never troubled by diarrhea (Fig. 3). These percentages decreased postoperatively to about 75% at 3 and 12 mo and to about 85% at 24 mo. The median preoperative score was 4 and decreased to a median postoperative score of 3 at 3 mo ( p < 0.001) and 24 mo ( p = 0.089) but increased again to 4 at 12 mo ( p = 0.023). About 80% of the patients were rarely or never troubled by constipation preoperatively, and similar results were

3 [(Fig._1)TD$FIG] EUROPEAN UROLOGY 60 (2011) Fig. 1 Patients responses preoperatively and at 3, 12 and 24 mo postoperatively to the question, How often during the past 2 weeks have you been troubled by stool frequency? reported at 3, 12, and 24 mo postoperatively (Fig. 4). The median preoperative score was 4 and remained so at 3 mo ( p = 0.99), 12 mo ( p = 0.12), and 24 mo ( p = 0.32) postoperatively. Patients seldom complained about uncontrolled stool loss. Preoperatively, about 95% of the patients were rarely or never troubled by uncontrolled stool loss, and similar results were reported at 3, 12, and 24 mo postoperatively (Fig. 5). The median preoperative score was 4 and remained so at 3 mo ( p = 0.56), 12 mo ( p = 0.69), and 24 mo ( p = 0.63) postoperatively. 4. Discussion To the best of our knowledge, this is the first prospective assessment of possible changes in bowel function after ileal resection for bladder substitution using validated [(Fig._2)TD$FIG] gastrointestinal questionnaires. Most of our patients reported they were rarely or never troubled by stool frequency, urgent bowel movements, diarrhea, constipation, or uncontrolled stool loss. Regarding stool frequency, urgent bowel movements, and diarrhea, we found some statistically significant differences between preand postoperative scores, especially due to shifts from rarely to never and vice versa. The possible explanation may be a change in bowel motility after abdominal surgery and the often observed postoperative delayed resumption of bowel function, a change in bowel flora after antibiotic intake in the perioperative phase, or the few months needed for the bowel to adapt after resection of cm. However, it should be taken into account that a statistically significant difference between never or rarely may not actually be of clinical relevance in everyday life. Fig. 2 Patients responses preoperatively and at 3, 12 and 24 mo postoperatively to the question, How often during the past 2 weeks have you been troubled by urgent bowel movements?

4 588 [(Fig._3)TD$FIG] EUROPEAN UROLOGY 60 (2011) Fig. 3 Patients responses preoperatively and at 3, 12, and 24 mo postoperatively to the question, How often during the past 2 weeks have you been troubled by diarrhea? The terminal ileum and the ileocecal valve are particularly important for resorption of nutrients, regulation of bowel emptying, and compensation for the loss of small bowel. Resection up to 60 cm of ileum is believed not to affect absorption if the terminal ileum and the ileocecal valve are left intact [1,10]. Resection >100 cm of ileum even with an intact terminal ileum and ileocecal valve results in lipid malabsorption [11]. Bile acids and vitamin B 12 are both absorbed solely in the terminal ileum, and bile acid is important for lipid absorption [12,13]. Bile acids are lost into the colon and lead to a reduction of sodium and water absorption, thus resulting in an increased stool frequency. If <100 cm of ileum are resected, increased hepatic synthesis can compensate the loss of bile acids [14 18]. In addition, the ileocecal valve regulates intestinal transit time. After ileocecal resection, intestinal transit [(Fig._4)TD$FIG] time is decreased and osmotic diarrhea can occur [19]. All these facts added together can cause diarrhea after terminal ileum and ileocecal valve resection. As a result of the fast transit time, fatty acids are not absorbed and are excreted with the stool predominantly as calcium salts (saponification) [1]. This results in both more soluble oxalate salts being absorbed in the colon and hyperoxaluria [1,20], which favors stone formation. Pfitzenmaier et al [7] performed a metabolic evaluation 5 16 yr after Mainz pouch 1 (resection of terminal ileum and ileocecal valve) and found a 14% incidence of upper tract urinary stones and a 32% incidence of periodic stool frequency. In contrast, increased stone formation was not observed after resection of cm of ileum when leaving the terminal ileum and the ileocecal valve intact [21]. Vitamin B 12 (cyanocobalamin) is absorbed in the ileum by a specific mechanism involving the intrinsic factor, a Fig. 4 Patients responses preoperatively and at 3, 12 and 24 mo postoperatively to the question, How often during the past 2 weeks have you been troubled by constipation?

5 [(Fig._5)TD$FIG] EUROPEAN UROLOGY 60 (2011) Fig. 5 Patients responses preoperatively and at 3, 12 and 24 mo postoperatively to the question, How often during the past 2 weeks have you been troubled by uncontrolled stool loss? glycoprotein secreted by parietal cells in the gastric mucosa [12,13]. Preservation of the distal cm terminal ileum has been shown to reduce B 12 malabsorption and bile acid loss, even in the absence of the proximal ileum [1]. In follow-up studies of the Kock pouch [22], for which cm of terminal ileum was used, up to 35% of patients required vitamin B 12 supplementation. Long-term follow-up (median: 9 yr) of the Mainz pouch 1 [7] demonstrated that 32% of patients who were not substituted at regular intervals had vitamin B 12 levels below the normal range. In our series of patients with ileal bladder substitution, where the terminal ileum was preserved, only 12% had subnormal vitamin B 12 at some time during follow-up, and 5% received vitamin B 12 substitution [23]. In summary, by sparing the terminal ileum and ileocecal valve (thereby avoiding ileocecal valve reconstruction as proposed by Fisch et al [4]), both the effects on bowel function and the metabolic complications are reduced. We therefore advocate the use of ileum to construct bladder substitutes. There are some limitations to this study. The quantity and the quality of diarrhea were not recorded in a frequency volume chart, and each patient may have had a different perception of the same amount of diarrhea. Although the GIQLI is a validated questionnaire, this instrument was not initially designed for urologic patients and is not urinary diversion specific. The dropout rate in completing the questionnaire at 2 yr is high for several reasons including bladder cancer and deaths unrelated to bladder cancer, a yet too short follow-up, and patients not completing the questionnaire for undetermined reasons. Thus the relatively low number of patients in the 2-yr group may limit the interpretation of the data at the 2-yr interval. A QOL questionnaire is not a diagnostic tool. It is a measure of subjective perception of a patient s sense of well-being. It cannot differentiate between different causes or diseases that may express the same symptoms. 5. Conclusions Preservation of the terminal ileum and the ileocecal valve is important in bladder substitution. No relevant subjective changes in bowel function are found after resection of cm of ileum if the terminal ileum and the ileocecal valve are left intact. Author contributions: Urs E. Studer had full access to all the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis. Study concept and design: Fung, Studer. Acquisition of data: Fung, Haeni. Analysis and interpretation of data: Fung, Kessler, Studer. Drafting of the manuscript: Fung, Kessler, Burkhard. Critical revision of the manuscript for important intellectual content: Burkhard, Studer. Statistical analysis: Kessler. Obtaining funding: None. Administrative, technical, or material support: None. Supervision: Studer. Other (specify): None. Financial disclosures: I certify that all conflicts of interest, including specific financial interests and relationships and affiliations relevant to the subject matter or materials discussed in the manuscript (eg, employment/ affiliation, grants or funding, consultancies, honoraria, stock ownership or options, expert testimony, royalties, or patents filed, received, or pending), are the following: None. Funding/Support and role of the sponsor: None. Acknowledgment statement: The authors gratefully acknowledge our professional nurse specialist, Katharina Ochsner, for excellent prospective questionnaire collection and quality data management.

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