Health-related Quality of Life in Patients Undergoing Ileal Ureter Replacement for Extensive Ureteral Stricture: A Prospective Multi-institutional Study.

Between January 2020 and July 2022, 100 patients consecutively underwent IUR ( Fig. 1 ). Finally, a cohort of 82 patients who met the eligibility criteria were included. Overall, 77 patients (93.9%) who returned completed questionnaires at 6 mo, and 79 (96.3%) at 12 mo after surgery, were evaluated. Table 1 summarizes clinical data for the cohort. The mean age was 44.6 yr and 52 patients (63.4%) were female. The main etiologies for extensive UrS were radiotherapy (33 patients, 40.2%) and iatrogenic injury during lithotripsy (19 patients, 23.2%). IUR was performed via an open approach in 17 patients (20.7%), a laparoscopic approach in 34 patients (41.5%), and a robotic approach in 31 patients (37.8%). The median operative time was 267.5 min (IQR 219–330) and the median ileal graft length was 25 cm (IQR 20–28). A significant improvement in renal function was observed: median serum creatinine decreased from 82.7 μmol/l (IQR 70.3–95.6) before surgery to 74.5 μmol/l (IQR 61.4–95.7) after surgery ( p  < 0.001). Over median follow-up of 48 mo, clinical success was observed in 81 patients (98.8%), with only one patient experiencing radiographic reobstruction. Clavien-Dindo grade III–IV complications occurred in eight patients (9.8%). There was a mild increase in long-term median serum creatinine to 89.0 μmol/l (IQR 75.9–103.0; p  = 0.001). Table 1 Baseline demographics, clinical and perioperative characteristics, and follow-up data for the study cohort Parameter Result Baseline demographics Patients ( n ) 82 Sex, n (%)  Male 30 (36.6)  Female 52 (63.4) Medan age, yr (standard deviation) 44.6 (11.8) Mean body mass index, kg/m 2 (standard deviation) 23.9 (3.3) Median HADS-anxiety score (interquartile range) 9 (7–10.25) Median HADS-depression score (interquartile range) 9 (8–10) Clinical characteristics Ureteral stricture etiology, n (%)  Iatrogenic injury during lithotripsy 19 (23.2)  Radiotherapy 33 (40.2)  Iatrogenic injury during surgery 9 (11.0)  Urinary tuberculosis 5 (6.1)  Ureteral polyp 5 (6.1)  Congenital disease 9 (11.0)  Trauma 1 (1.2)  Endometriosis 1 (1.2) Side affected, n (%)  Left 31 (37.8)  Right 18 (22.0)  Bilateral 33 (40.2) Prior failed reconstruction, n (%) 28 (34.1) Perioperative characteristics Surgical approach, n (%)  Open 17 (20.7)  Laparoscopic 34 (41.5)  Robotic 31 (37.8) Median operative time, min (interquartile range) 267.5 (219–330) Median estimated blood loss, ml (interquartile range) 85 (50–150) Median postoperative hospital stay, d (interquartile range) 14 (10–16) Median ileal graft length, cm (interquartile range) 25 (20–28) Follow-up Median follow-up, mo (interquartile range) 48 (43–58) Postoperative CD grade III–IV complication, n (%) 8 (9.8) Clinical success, n (%) 81 (98.8) Median serum creatinine, μmol/l (interquartile range)  Preoperative 82.7 (70.3–95.6)  Postoperative 74.5 (61.4–95.7)  Final follow-up 89.0 (75.9–103.0) CD = Clavien-Dindo. Baseline demographics, clinical and perioperative characteristics, and follow-up data for the study cohort CD = Clavien-Dindo. Patients with extensive UrS presented with significantly lower HRQoL scores at baseline in comparison to the general Chinese population for all SF-36 domains [18] ( Supplementary Fig. 1 ). Scores for each domain are shown in Supplementary Table 1 . Longitudinal changes in HRQoL scores for different domains are shown in Fig. 4 . Comparison of median 6-mo and 12-mo scores to those at baseline revealed statistically significant changes in all SF-36 domains (all p  < 0.001; Table 2 ). Specifically, at 6 mo after surgery, between 45.5% and 79.2% of patients reported a significant improvement in HRQoL across the different domains; this proportion ranged from 46.8% to 74.7% at 12 mo after surgery ( Supplementary Table 2 ). Fig. 4 Radar plot of longitudinal changes in mean scores for different domains of the 36-item Short Form Survey. Higher scores indicate better HRQoL. PF = physical function; RP = role-physical; BP = bodily pain; GH = general health; VT = vitality; SF = social functioning; RE = role-emotional; MH = mental health; HRQoL = health-related quality of life. Table 2 Short Form Survey-36 scores by domain during follow-up Domain Median score (interquartile range) p value vs baseline a p value b Baseline 6 mo 12 mo 6 mo 12 mo Physical function 75 (60–90) 90 (80–95) 95 (85–100) <0.001 <0.001 <0.001 Role-physical 0 (0–50) 87.5 (25–100) 100 (25–100) <0.001 <0.001 <0.001 Bodily pain 64 (52–80) 74 (64–84) 84 (62–100) <0.001 <0.001 <0.001 General health 46 (35–62) 62 (45–77) 64.5 (52–82) <0.001 <0.001 <0.001 Vitality 55 (40–75) 75 (60–80) 75 (60–85) <0.001 <0.001 <0.001 Social functioning 62.5 (37.5–75) 87.5 (75–100) 87.5 (75–100) <0.001 <0.001 <0.001 Role-emotional 0 (0–100) 100 (66.7–100) 100 (66.7–100) <0.001 <0.001 <0.001 Mental health 64 (44–76) 76 (56–80) 76 (64–84) 0.009 <0.001 <0.001 a p value for a Wilcoxon signed-rank test comparing the 6-mo or 12-mo score to the baseline value. b p value for a Friedman test comparing the change in score during follow-up. Radar plot of longitudinal changes in mean scores for different domains of the 36-item Short Form Survey. Higher scores indicate better HRQoL. PF = physical function; RP = role-physical; BP = bodily pain; GH = general health; VT = vitality; SF = social functioning; RE = role-emotional; MH = mental health; HRQoL = health-related quality of life. Short Form Survey-36 scores by domain during follow-up p value for a Wilcoxon signed-rank test comparing the 6-mo or 12-mo score to the baseline value. p value for a Friedman test comparing the change in score during follow-up. Preoperatively, 73.2% (60/82) of patients reported symptoms of anxiety (HADS-anxiety score ≥ 8) and 80.5% (66/82) reported symptoms of depression (HADS-depression score ≥ 8; Fig. 5 ). In comparison to baseline, the prevalence of anxiety symptoms was significantly lower at 12 mo after surgery (57.0%, 45/79 patients; p  = 0.031), but the decrease at 6 mo (59.7%, 46/77 patients) was not statistically significant ( p  > 0.05). By contrast, the prevalence of depression symptoms showed no significant changes at either 6-mo (84.4%, 65/77 patients) or 12-mo (87.3%, 69/79 patients) follow-up in comparison to baseline (both p  > 0.05). Fig. 5 Longitudinal changes in anxiety and depression according to the Hospital Anxiety and Depression Scale (HADS). Percentage of patients with and without (A) anxiety (* p  ≤ 0.05) and (B) depression over time. Longitudinal changes in anxiety and depression according to the Hospital Anxiety and Depression Scale (HADS). Percentage of patients with and without (A) anxiety (* p  ≤ 0.05) and (B) depression over time.

From January 2020 to July 2022, consecutive patients undergoing IUR for extensive UrS at four centers were invited to participate in the study. Surgical indications included extensive (>5 cm in length) or multiple UrSs, either unilateral or bilateral, with or without bladder contracture. The inclusion criteria were as follows: (1) age 18–75 yr; (2) a diagnosis of extensive UrS for which IUR was scheduled; (3) able to read and write in Chinese; (4) able to complete the questionnaire via mobile phone or computer; and (5) willing to adhere to scheduled follow-up. The exclusion criteria were: (1) refusal or unable to provide informed consent; (2) illiterate; (3) disabilities; and (4) simultaneous other reconstruction procedure. The study followed the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) reporting guideline [14] . Informed consent was obtained from all subjects who met the inclusion criteria and agreed to participate in the study, which was carried out in accordance with the Principles of the Declaration of Helsinki. We prospectively interviewed a final cohort of 82 consecutive patients for the study ( Fig. 1 ). Fig. 1 Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) diagram of study enrollment and the final analysis cohort. IUR = ileal ureter replacement. Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) diagram of study enrollment and the final analysis cohort. IUR = ileal ureter replacement. The surgical approach (open, laparoscopic, or robot-assisted) was chosen on the basis of surgeon expertise and patient characteristics by experienced surgeons. The procedure commenced with meticulous adhesiolysis and thorough mobilization of the affected ureter and the intended ileal segment. Intraoperatively, the strictured ureteral segments were meticulously evaluated via reference to preoperative imaging findings, and were then replaced with an appropriately sized ileal segment harvested proximal to the ileocecal valve. For unilateral strictures, the proximal end of the ileal segment was anastomosed to the ureteral stump or renal pelvis in an end-to-end or end-to-side fashion, while the distal end was fashioned into an antireflux nipple and anastomosed to the bladder ( Fig. 2 ). In cases with bilateral strictures, the ileal segment was configured in a “reverse 7”, “7” or “Y” shape according to the location and length of the defects to ensure isoperistaltic orientation and a tension-free anastomosis ( Fig. 3 ). Patients diagnosed with bladder contracture simultaneously underwent ileal augmentation cystoplasty. Fig. 2 Technique for ileal ureter replacement. (A) Meticulous adhesiolysis and mobilization of the affected ureter. (B) Resection of the strictured ureteral segment with preservation of the proximal ureteral stump. (C) Harvesting of an appropriately sized ileal segment for the defect length measured. (D) Creation of an antireflux nipple at the distal end of the isolated ileal segment. (E) Anastomosis between the proximal ureteral stump and the ileal segment. (F) Implantation of the distal ileal segment into the bladder. Fig. 3 Preoperative and postoperative urography for bilateral ileal ureter replacement. Red dotted lines show the edges of the ureteral (or duplex ureteral) strictures. Yellow dotted lines show the edges of the ileal ureter. (A) Reverse 7-shaped bilateral ileal ureter replacement. (B) 7-shaped bilateral ileal ureter replacement. (C) Y-shaped bilateral ileal ureter replacement. Technique for ileal ureter replacement. (A) Meticulous adhesiolysis and mobilization of the affected ureter. (B) Resection of the strictured ureteral segment with preservation of the proximal ureteral stump. (C) Harvesting of an appropriately sized ileal segment for the defect length measured. (D) Creation of an antireflux nipple at the distal end of the isolated ileal segment. (E) Anastomosis between the proximal ureteral stump and the ileal segment. (F) Implantation of the distal ileal segment into the bladder. Preoperative and postoperative urography for bilateral ileal ureter replacement. Red dotted lines show the edges of the ureteral (or duplex ureteral) strictures. Yellow dotted lines show the edges of the ileal ureter. (A) Reverse 7-shaped bilateral ileal ureter replacement. (B) 7-shaped bilateral ileal ureter replacement. (C) Y-shaped bilateral ileal ureter replacement. Data for all patients were prospectively collected in our Reconstruction of Urinary Tract: Technology, Epidemiology and Result (RECUTTER) database. We used the 36-item Short Form Health Survey (SF-36) and the Hospital Anxiety and Depression Scale (HADS) [15] to measure HRQoL and mental health, respectively. Patients received the questionnaire 3 d before surgery for completion via confidential self-administration, and at 6 mo and 12 mo after surgery. All participants were followed up at the next scheduled time irrespective of whether they responded at the previous time point. HRQoL was assessed using SF-36 (Chinese version 2.0), which is a generic and validated questionnaire [16] comprising 36 items that measure all eight health aspects considered necessary to measure HRQoL: physical function (PF), role limitation due to physical health (RP), bodily pain (BP), general health perception (GH), vitality (VT), social function (SF), role limitation due to emotional problems (RE), and mental health (MH). Each domain consists of between two and ten items that are evaluated using a 2–6-point Likert scale. The scores for these domains range from 0 to 100. Higher scores indicate better HRQoL. The Chinese version of HADS was used to measure the level of anxiety and depression in participants. The scale has been validated in the Chinese population and is widely used to evaluate anxiety and depression, with good screening utility [17] . HADS is a 14-item questionnaire comprising two seven-item subscales that assess anxiety and depression using 4-point Likert scales. For either anxiety or depression, the total score ranges from 0 to 21. Higher scores indicate a higher level of anxiety or depression. Results are reported as the mean and standard deviation for normally distributed continuous variables, as the median and interquartile range (IQR) for non–normally distributed continuous variables, and as the frequency and proportion for categorical variables. T test was used to compare HRQoL for patients in this study to results from a previous study in a general Chinese population [18] . The Friedman test was used to compare longitudinal changes in scores over time. A Wilcoxon signed-rank test was used to compare follow-up scores to baseline values. Clinical success was defined as symptom-free status and no radiographic evidence of reobstruction at scheduled follow-up visits conducted according to a standardized protocol across all participating centers, as previously described [6] . A significant improvement in HRQoL was defined as in improvement of more than 10 points in follow-up score in comparison to the baseline score [19] . All analyses were performed using a complete-case approach without imputation for missing data. A two-tailed p value of < 0.05 was deemed statistically significant. All data were analyzed using SPSS 26.0 (SPSS, Chicago, IL, USA).

This study provides the first comprehensive and longitudinal evaluation of HRQoL following IUR. Although patients with extensive UrS presented with significantly lower HRQoL at baseline in comparison to the general Chinese population, they experienced a marked improvement in HRQoL following IUR. Most patients reported significant improvements in different SF-36 domains within 12-mo follow-up. Although the preoperative assessment was conducted shortly before surgery, which is a time when anxiety levels are typically elevated and may have contributed to lower baseline scores, the substantial and sustained magnitude of improvements observed across all HRQoL domains strongly supports the meaningful clinical benefit of IUR. These data provide strong evidence that IUR led to substantial improvements in patient-reported HRQoL within the first 1 yr after IUR surgery. QoL is increasingly being recognized as an important health factor when making medical decisions and counseling families. Previous IUR studies have mainly focused on the surgical technique and outcomes. To the best of our knowledge, this is the first study to longitudinally document HRQoL changes after IUR for extensive UrS using patient-reported measures. According to our findings, scores for all SF-36 domains significantly increased at 6 mo and 12 mo after IUR surgery. These satisfactory results could be linked to surgical alleviation of symptoms and the avoidance of long-term indwelling nephrostomy tubes or ureteral stents. Our findings could potentially help in preoperative counseling as a standard for HRQoL changes that patients can expect, and might also improve the confidence of surgeons and patients in the use of ileal grafts for IUR. Beyond specific associations with the surgical approach, it is important to contextualize our core finding of significant HRQoL improvements after IUR within the broader literature. There has been limited research on the effect of reconstructive surgery on patient-reported HRQoL, even though the primary objective is to preserve renal function and improve QoL. Specifically, just one prospective study evaluated patient-reported HRQoL: using the SF-8 instrument, Sahai et al [20] found a significant improvement in mental HRQoL but not physical HRQoL at 6 wk after upper urinary tract laparoscopy. Unfortunately, the study was limited by short-term follow-up and evaluation of a heterogeneous population; only eight patients underwent reconstructive surgery/pyeloplasty. Consistent with our findings, a prospective HRQoL assessment for pediatric patients with ureteropelvic junction obstruction using Pediatric Quality of Life Inventory 4.0 by Parekh et al [10] , revealed that patients reported significant improvements in HRQoL scores 6 mo after pyeloplasty in comparison to baseline scores. However, the results may not be directly comparable to our study because of differences in the study populations and surgical procedures. Patients in our study had more serious conditions and comorbidities, particularly the extensive UrS, which necessitated more invasive and complex ureteral reconstruction with bowel segments. Further prospective research is required to validate and extend our findings. The most salient finding from our prospective study is the documentation of a substantial and simultaneous improvement across all SF-36 domains within the first year following IUR. The broad improvement in both physical and mental components of HRQoL underscores the profound positive impact that successful IUR can have on a patient’s life. This subjective benefit was corroborated by objective evidence of improvements in renal function. The significant reduction in serum creatinine levels shortly after surgery unequivocally demonstrates the efficacy of IUR in relieving obstruction and restoring renal function. Notably, the mild elevation of creatinine observed at long-term follow-up is consistent with previous long-term IUR series [21] . This trend underscores the necessity of continuous monitoring beyond the initial postoperative period to safeguard the enduring success of IUR surgery. It is crucial to contextualize this finding against the historical backdrop for this procedure. Previous negative IUR results have prompted individuals to pursue alternative therapies such as ureteral stents, percutaneous nephrostomy, or even nephrectomy, which may provide inferior functional outcomes and poor HRQoL [2] , [4] . Our data compellingly argue against this paradigm, and demonstrate that when is IUR is successfully performed, it is a powerful intervention for restoring QoL. Despite the relatively high incidence of Clavien-Dindo grade III–IV complications (9.8%), our study cohort experienced a significant improvement in HRQoL within the first 12 mo after IUR. This finding demonstrates that IUR is a highly effective procedure for managing extensive UrSs, with benefits in restoring QoL that substantially outweigh the associated surgical risks. However, it is worth noting that most previous studies have focused on open surgery, and that robotic or laparoscopic surgery has been associated with favorable functional outcomes and acceptable complication rates in this setting [6] , [7] . The technical advantages of the robotic platform—such as superior three-dimensional visualization, enhanced dexterity, and precision—are particularly suited to the complexities of IUR, which involves meticulous bowel work and delicate ureteroileal anastomoses, often in a reoperative field [6] , [7] . These technical benefits probably contribute to reducing the physiological stress of the procedure, with potential for lower pain levels and more rapid convalescence, thereby allowing patients to reap the QoL benefits of the reconstruction itself at an earlier time point. The importance of aligning the physiological demands of a procedure with patient capacity is increasingly recognized in urological reconstruction. This is exemplified by recent evidence for radical cystectomy with an ileal neobladder: an age threshold of 70 yr has been identified, beyond which patients are less likely to achieve good HRQoL, as major bowel-based urinary diversion places significant demands on physiological reserves [22] . While a direct age comparison is not applicable given our younger cohort (mean age 44.6 yr), this principle highlights the fact that the complexity of IUR necessitates careful patient selection. The favorable HRQoL outcomes we observed may thus be partly attributable to the good physiological reserve of our cohort; for such patients, the technical precision of contemporary minimally invasive approaches can optimize more rapid recovery. A narrative of rapid physical recovery stands in intriguing contrast to the more gradual and complex trajectory of psychological recovery. Despite the marked improvement in self-reported physical health and function, our longitudinal HADS data revealed that the high burden of psychological distress at baseline was not immediately alleviated. The prevalence of anxiety symptoms only showed a significant decline by the 12-mo follow-up, and depressive symptoms remained persistently elevated throughout the first postoperative year. This dissociation suggests that while IUR effectively addresses the physical source of suffering, relief from psychological distress—potentially compounded by longstanding illness and ongoing concerns about renal function and long-term outcomes—may require a longer period of adjustment. This finding underscores the critical need for integration of routine psychological assessment and targeted support into the perioperative care pathway for these patients to ensure that their mental wellbeing keeps pace with their physical recovery. Our study results may be valuable for several reasons. First, they might be useful in counseling patients before surgery in order to appropriately explain the probability and time line for significant improvements in HRQoL. Furthermore, the observation that a substantial proportion (approx. 30–60%) of patients did not achieve significant HRQoL improvements across different domains within the first year highlights an important area for further investigation. These insights are valuable for managing expectations and for guiding future research aimed at identifying the factors associated with HRQoL outcomes to enhance patient care. Ultimately, a better understanding of these factors could enable health care professionals to provide more personalized and timely interventions to achieve better medical care and improvements in QoL for patients undergoing this procedure. Our study has several limitations. First, the use of a generic HRQoL instrument (SF-36) rather than a disease-specific questionnaire may lack sensitivity for capture of all nuances of the condition. Second, the statistical comparisons across multiple SF-36 domains and time points, without formal correction for multiple testing, increase the risk of a type I error. Coupled with the exclusion of illiterate patients, these factors may affect the precision of our psychological assessment and limit the generalizability of our findings to a broader, more socioeconomically diverse population. Second, the preoperative HRQoL assessment was conducted shortly before surgery, which is a time of typically elevated anxiety, and may have contributed to lower baseline scores and potentially amplified the improvement observed. The absence of a comparator group (eg, patients managed with nephrostomy or nephrectomy) prevents direct comparative effectiveness inferences. Furthermore, clinical heterogeneity was introduced as some patients underwent concomitant augmentation cystoplasty. Although median clinical follow-up was 48 mo, HRQoL follow-up was limited to 12 mo, which may be insufficient to evaluate long-term HRQoL trends despite the clinical durability of the procedure.

Our study confirms the safety and efficacy of IUR for complex ureteral reconstruction. IUR in this setting provides favorable HRQoL improvements in most domains within 12 mo. Author contributions : Xuesong Li 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 : Z. Li, Xuesong Li. Acquisition of data : Z. Li, X. Wang, D. Li, Ma, Liu, Xinfei Li, K. Yang, B. Wang, P. Zhang, Zhu, Guan, J. Yang. Analysis and interpretation of data : X. Wang, D. Li. Drafting of the manuscript : X. Wang, D. Li, Han. Critical revision of the manuscript for important intellectual content : Z. Li, K. Zhang, Xuesong Li. Statistical analysis : X. Wang, Han. Obtaining funding : Z. Li, Xuesong Li. Administrative, technical, or material support : K. Yang, Liu, P. Zhang, Zhu, Han, Ma. Supervision : Z. Li, K. Yang, Xuesong Li, Zhou, K. Zhang. Other : None. Financial disclosures : Xuesong Li certifies 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 : This study was supported by grants from the National High Level Hospital Clinical Research Fund (Scientific Research Seed Fund of Peking University First Hospital ; grant 2022SF78 ). The funding body played a role in the design and conduct of the study. Ethics statement : This study was approved by the ethics committee of Peking University First Hospital (approval numbers 2019134 and 2022273). All procedures were performed in accordance with the Declaration of Helsinki. All patients signed written informed consent. Data sharing statement : The data that support the findings of this study are available from the corresponding author upon reasonable request.

Ileal ureter replacement (IUR) is considered the ultimate resort for extensive ureteral defects that are not amenable to other reconstructive methods [1] , [2] . The main advantage of this procedure is the long-term avoidance of nephrostomy tubes and ureteral stents, which significantly reduce patients’ quality of life (QoL) [3] . Given the technical complexity and potential postoperative complications, IUR has predominantly been performed by experienced surgeons via an open approach [2] , [4] , [5] . Increasing surgical experience in the use of minimally invasive methods has reduced the postoperative complication rate [6] , [7] , [8] . Unfortunately, many patients with extensive ureteral stricture (UrS) are often managed with long-term conservative drainage options rather than reconstruction, primarily owing to concerns about potential morbidity and lack of familiarity with technically demanding ureteral repair. This is particularly consequential, as these patients often suffer from severely impaired health-related QoL (HRQoL) because of their condition. The underlying ureteral obstruction can lead to chronic flank pain, recurrent urinary tract infections, and renal dysfunction. More profoundly, long-term dependence on nephrostomy tubes or ureteral stents, which are often required for management, directly impacts patients’ daily life [9] . One of the major treatment goals of any surgical intervention, especially in reconstructive surgery, is to improve patients’ HRQoL [10] , [11] . Although the technical nuances and postoperative complications of IUR have been well documented [12] , [13] , there is a scarcity of data on longitudinal changes in HRQoL associated with ureteral reconstruction using a bowel segment. This is despite evidence that patients with UrS exhibit heightened psychological distress and poor HRQoL [3] . To better characterize the contemporary impact of IUR on HRQoL, we conducted a prospective longitudinal study to collect HRQoL data over a 1-yr follow-up period. Our primary objective was to characterize the pattern and extent of HRQoL improvements following IUR across the many validated measures collected.