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Mortality following augmentation cystoplasty: A transitional urologist's viewpoint

  • D.A. Husmann
    Correspondence
    Correspondence to: D.A. Husmann, Department of Urology, 200 First St SW, Mayo Clinic, Rochester, MN 55905, USA, Tel.: +1 507 266 4446; fax: +1 507 284 3951
    Affiliations
    Department of Urology, 200 First St SW, Mayo Clinic, Rochester, MN 55905, USA
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Open AccessPublished:June 03, 2017DOI:https://doi.org/10.1016/j.jpurol.2017.05.008

      Summary

      Introduction

      Three complications have been hypothesized to increase patient mortality following enterocystoplasty: spontaneous bladder perforation, bladder neoplasia, and chronic renal failure (CRF). The present study examined risk of their occurrence and discussed ways to improve the quality of care.

      Materials and methods

      The present transitional clinic followed 385 patients with a history of bladder augmentation using either ileal, sigmoid, or ascending colon. The median age was 37 years (range 16–71). Median follow-up interval after augmentation was 26 years (range 2–59).

      Discussion

      Spontaneous rupture of the bladder occurred in 3% (13/385), with one associated death (0.25%, 1/385). Spontaneous bladder rupture significantly correlated with substance abuse, non-compliance with catheterization, and mental/physical disabilities that required the use of surrogates to perform and monitor intermittent catheterization (P < 0.01).
      Of the 203 patients that were followed for ≥10 years, 4% (8/203) developed a bladder tumor. In comparison, 2.5% (5/203) of an age-matched control population, managed by anticholinergics and intermittent catheterization, developed a bladder tumor. Therefore, enterocystoplasty cannot be associated with an increased risk of cancer development (P = 0.397).
      Chronic renal failure ≥ Stage 3 arose in 15% (58/385), and 1% (4/385) of the patients died as a result of this complication. Obese patients (BMI ≥30) catheterizing per urethra were more likely to be non-compliant with catheterization and develop CRF compared with obese patients with a continent catheterizable stoma (P > 0.001). These findings suggest that compliance with intermittent catheterization and renal preservation are enhanced by the presence of a catheterizable abdominal stoma.

      Conclusion

      The individual's intellectual and physical capability to obey medical directives, refrain from high-risk habits, maintain a healthy weight, and comply with long-term follow-up visits were all critical to the enduring success of bladder augmentation.

      Keywords

      Introduction

      Goals of reconstructive surgery

      The primary purpose of any reconstructive procedure is to provide the highest quality of life with the lowest potential for complications. Success is therefore measured by the operations ability to meet four primary objectives: preservation of life, preservation of renal function, creation or preservation of urinary continence, and creation or preservation of sexual function. One major caveat to consider in reaching these objectives is that at no time should one of the lesser goals trump those that go before it. This review was framed from the viewpoint of a transitional urologist, with its primary objective being to provide the pediatric urologist insight into the long-term success of enterocystoplasty in its ability to meet the first key objective: preservation of life.

      Considerations when interpreting the data

      The incidence of post-surgical complications following urologic reconstructive surgery varies from study to study. Variation is based on the length of follow-up, the type of augmentation performed, the use of concurrent bladder outlet obstructive procedures, the presence of continent abdominal stomas, and the patient's ability to comply with medical directives [
      • Schlomer B.J.
      • Copp H.L.
      Cumulative incidence of outcomes and urologic procedures after augmentation cystoplasty.
      ,
      • Husmann D.
      Long-term complications following bladder augmentations in patients with spina bifida; bladder calculi, perforation of the augmented bladder and upper tract deterioration.
      ,
      • Schlomer B.
      • Saperston K.
      • Baskin L.
      National trends in augmentation cystoplasty in the 2000's and factors associated with patient outcomes.
      ,
      • Lee R.K.
      • 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.
      ,
      • Metcalfe P.
      • Cain M.
      • Kaefer M.
      • Gilley D.A.
      • Meldrum K.K.
      • Misseri R.
      • et al.
      What is the need for additional bladder surgery after bladder augmentation in childhood.
      ,
      • DeFoor W.
      • Minevich E.
      • Reddy P.
      • Sekhorn D.
      • Polsky E.
      • Wackson J.
      • et al.
      Bladder calculi after augmentation cystoplasty; risk factors and prevention strategies.
      ].
      In reviewing any data from a transitional urology clinic it is important to note that during the past three decades there has been a continual evolution in the management of infants and children with congenital urologic abnormalities. Notably, advances in neonatal and pediatric care have resulted in significantly more individuals who are born with a complex congenital anomaly to survive into adulthood [
      • Moon P.
      • Bovijin L.
      • DBudt W.
      • Belmans A.
      • Gewillig M.
      Temporal trends in survival to adulthood: patients born with congenital heart disease from 1970 to 1992 in Belgium.
      ,
      • Downard C.
      • Jaksic T.
      • Garza J.
      • Nemes L.
      • Jennings R.
      • Wilson J.M.
      Analysis of an improved survival rate for congenital diaphragmatic hernia.
      ]. In contrast, the use of dietary supplements such as folic acid and the utilization of therapeutic abortions for the treatment of fetuses with severe congenital anomalies have decreased the incidence of these defects [
      • Woodhouse C.
      Adolescent and transtional urology.
      ]. Additionally, the proliferation of ongoing quality care projects that may favorably impact patient care may also have impacted the outcome data [
      • Husmann D.
      Long-term complications following bladder augmentations in patients with spina bifida; bladder calculi, perforation of the augmented bladder and upper tract deterioration.
      ,
      • McGuire E.
      Urodynamics of the neurogenic bladder.
      ,
      • Crytzer T.
      • Dicianno B.
      • Kapoor R.
      Physical activity, exercise and health-related measures of fitness in adults with spina bifida: a review of the literature.
      ,
      • Cody J.D.
      • Nabi G.
      • Dublin N.
      • McClinton S.
      • Neal D.E.
      • Pickard R.
      • et al.
      Urinary diversion and bladder reconstruction/replacement using intestinal segments for intractable incontinence or following cystectomy.
      ,
      • Webb T.
      Optimizing health care for adults with spina bifida.
      ]. Indeed, the patients that are currently being seen in transitional clinics and reported on in this paper may not mirror those of future generations.

      Bladder augmentation and complications that impact the preservation of life

      Three long-term complications of bladder augmentation have been hypothesized or documented to be associated with the subsequent death of the patient: perforation of the bladder augment, development of bladder neoplasia, and the onset of end-stage renal disease (ESRD) [
      • Husmann D.
      Long-term complications following bladder augmentations in patients with spina bifida; bladder calculi, perforation of the augmented bladder and upper tract deterioration.
      ,
      • Robertson J.
      • Lemolo F.
      • Stabler S.
      • Allen R.H.
      • Spence J.
      Vitamin B12, homocysteine and carotid plaque in the era of folic acid fortification of enriched cereal grain products.
      ,
      • Go A.
      • Chertow G.
      • Fan D.
      • et al.
      Chronic kidney disease and the risks of cardiovascular events and hospitalization.
      ].

      Method

      Study population

      The transitional clinic followed 385 patients with a history of bladder augmentation using either ileal, sigmoid, or ascending colon. The median age of patients in this clinic was 37 years (range 16–71). The median age at the time of bladder augmentation was 11 years (range 2–16). Follow-up interval from the time of augment was defined as the number of years the enteric tract had been exposed to urine. In 26 patients, ileal conduits had initially been performed followed by urinary Undiversion, with the incorporation of the conduit into the augmented bladder. In this patient population, the follow-up interval began at the time of ileal conduit formation, not augmentation. Median follow-up interval after the enteric tract was exposed to urine was 26 years (range 2–59) [
      • Higuchi T.T.
      • Granberg C.F.
      • Fox J.A.
      • Husmann D.A.
      Augmentation cystoplasty and risk of neoplasia: fact, fiction and controversy.
      ,
      • Higuchi T.T.
      • Fox J.A.
      • Husmann D.A.
      Annual endoscopy and urine cytology for the surveillance of bladder tumors after enterocystoplasty for congenital bladder anomalies.
      ]. The underlying reasons for a bladder augmentation were: neurogenic bladder in 62% (237/385), exstrophy–epispadias complex in 22% (85/385), PUV in 11% (42/385), and a variety of miscellaneous etiologies in 5% (21/385).

      Spontaneous bladder perforation

      A total of 3% (13/385) of patients developed a spontaneous rupture of the bladder, with one associated death (0.25%, 1/385). The majority of spontaneous bladder ruptures were directly related to either substance abuse or patient non-compliance with catheterization. Specifically, during a 25-year time span, 203/385 patients, aged 16–53 years, were screened for the presence of alcohol abuse and/or non-compliance with medical directives regarding CIC. Alcohol abuse was defined per criteria outlined by the National Institute on Alcohol Abuse and Alcoholism [
      • NIOAAA
      National institute on alcohol abuse and alcholism: alcohol facts and statistics.
      ]. Patients were considered to abuse alcohol if the individual: routinely had >14 drinks per week, and/or participated in binge drinking, defined as having >4–5 drinks over a 2-h period at least one day per month [
      • NIOAAA
      National institute on alcohol abuse and alcholism: alcohol facts and statistics.
      ]. Failure to be compliant with CIC was defined as the patient admitting to catheterizing ≤3 times per day on a routine basis [
      • Husmann D.
      Long-term complications following bladder augmentations in patients with spina bifida; bladder calculi, perforation of the augmented bladder and upper tract deterioration.
      ,
      • Fox J.A.
      • Husmann D.A.
      Continent urinary diversion in childhood: complications of alcohol abuse developing in adulthood.
      ]. Median age of patients involved in the study was 24 years (range 16–53). Of these patients, 12% (24/203) admitted to a history of alcohol abuse, 17% (4/24) had a coexisting chemical dependency. An additional 6% (12/203) became non-compliant with catheterization, but did not give a history of substance abuse. Of the 36 patients with a history of substance abuse or non-compliance with medical directives, 22% (8/36) experienced spontaneous bladder rupture; 14 bladder ruptures and one death occurred within this patient population. Two of these patients, 0.5% (2/385) of the total patient population, were eventually converted to ileal conduits due to repeated bladder perforations (n = 3) and failure to gain sobriety. It is noteworthy that in patients with non-compliance with catheterization, a diagnosis of intellectual disability was present in 50% (6/12). In the 167 patients who were compliant with intermittent catheterization routines and did not have a history of substance abuse, 1% (2/167) had a spontaneous bladder rupture, and no deaths were reported (P = 0.006) [
      • Husmann D.
      Long-term complications following bladder augmentations in patients with spina bifida; bladder calculi, perforation of the augmented bladder and upper tract deterioration.
      ,
      • Fox J.A.
      • Husmann D.A.
      Continent urinary diversion in childhood: complications of alcohol abuse developing in adulthood.
      ].
      The 12% incidence of alcohol abuse found in adults with an enterocystoplasty mirrored the rate found within the population of the United States, where 8–17% of individuals become alcohol or substance dependent; this incidence depends upon sex and age of the person [
      • NIOAAA
      National institute on alcohol abuse and alcholism: alcohol facts and statistics.
      ,
      • Fox J.A.
      • Husmann D.A.
      Continent urinary diversion in childhood: complications of alcohol abuse developing in adulthood.
      ,
      • Fitzgerald K.
      15 shocking alcohol statistics for alcohol awareness.
      ]. The physiological effects and consequences of alcohol consumption following enterocystoplasty cannot be understated. The development of alcohol-induced diuresis, coexisting with impaired mental and physical abilities provoked by alcohol intoxication, provides the ‘perfect storm’ with which to induce a spontaneous bladder rupture.
      It is also important to note the association of mental impairment/deficiency with the failure to be compliant with medical directives [
      • Husmann D.
      Long-term complications following bladder augmentations in patients with spina bifida; bladder calculi, perforation of the augmented bladder and upper tract deterioration.
      ,
      • Fox J.A.
      • Husmann D.A.
      Continent urinary diversion in childhood: complications of alcohol abuse developing in adulthood.
      ]. Specifically, the correlation between mental impairment and non-compliance with catheterization becomes manifest in the maturing patient, as they become less reliant on their parents, move into group homes and/or their elderly parents develop mental or physical disabilities. Indeed, due to the patient becoming either physically unable to perform catheterization (n = 2) or an inability to find surrogates to perform catheterization (n = 8), the institution managed 2.5% (10/385) of patients with a chronic, indwelling, 22–24F suprapubic tube (SP). During a median follow-up interval of 7 years following placement of an SP tube (range 2–12), all 10 patients who were managed in this fashion developed complications (Table 1). To prevent mucous plugging of the catheter and stone formation, it was attempted to manage these patients with daily bladder irrigations with >240 ml fluid daily. Unfortunately, a surrogate was often unable to be found to perform this, and non-compliance with this directive was universal. Eventually, due to multiple urologic complications, 20% (2/10) of patients managed with a suprapubic tube, or 0.5% (2/385) of the entire cohort underwent takedown of their augmented bladder and had conversion to a urinary conduit.
      Table 1Follow-up of patients managed by a 22–24 F suprapubic tube placed within the augmented bladder.
      Complications notedPercent of patients with complications
      Perivesical or intraperitoneal abscesses arising from urine extravasated from augmented bladder or SP tube site20% (2/10)
      Dislodgement of SP tube and loss of tract requiring emergent decompression30% (3/10)
      Repetitive bladder stones60% (6/10)
      Sepsis arising from complications from SP tube management60% (6/10)
      Intermittent obstruction of SP tube requiring ER visit100% (10/10)
      Conversion to ileal conduit due to multiple urologic complications20% (2/10)
      Median follow-up interval of 7 years (range 2–12).
      SP, suprapubic; ER, emergency room.
      Note: Patients may have had more than one complication or more than one recurrence of the complication.
      For the last 10 years the present institution has intensively focused efforts on educating the patient before proceeding with an enterocystoplasty, due to the dire consequences of spontaneous bladder rupture and/or complications arising from the management of the augmented bladder with an indwelling suprapubic tube. Specifically, the patient is instructed on the need for catheterization to be performed a minimum of four times daily; the need for large-volume bladder irrigations to prevent bladder stone formation (>250 ml per day); and the necessity to refrain from risky behavior, mainly being excess alcohol intake and use of illegal/illicit drugs [
      • Husmann D.
      Long-term complications following bladder augmentations in patients with spina bifida; bladder calculi, perforation of the augmented bladder and upper tract deterioration.
      ,
      • Fox J.A.
      • Husmann D.A.
      Continent urinary diversion in childhood: complications of alcohol abuse developing in adulthood.
      ,
      • Metcalfe P.
      • Casale A.
      • Kaefer M.M.
      • Misseri R.
      • Dussinger A.
      • Meldrum K.
      Spontaneous bladder perforation in augmentation cystoplasty during urodynamic investigation: a report of 500 augmentations in children and analysis risk.
      ]. The institution refuses to proceed with an augmentation until the individual who is undergoing the procedure documents mastery regarding the knowledge and skill to perform the necessary post-operative care. However, it is cautioned that even though this course of preventive treatment has vigorously been pursued, problems can still ensue. Even now, despite strenuous pre-operative instructions and close post-operative follow-up, patients become non-compliant with medical directives. It is therefore felt that it should be mandatory to ask appropriately directed social questions regarding both alcohol consumption and compliance with medical guidelines, as they are a crucial part of long-term patient management.

      Neoplasia within bladder augmentations

      During the last 30 years the present institution has managed eight patients with tumors that arose within an augmented bladder, which is a total of 2% (8/385) of the total patient population [
      • Higuchi T.T.
      • Granberg C.F.
      • Fox J.A.
      • Husmann D.A.
      Augmentation cystoplasty and risk of neoplasia: fact, fiction and controversy.
      ,
      • Husmann D.A.
      • Rathbun S.R.
      Long-term follow-up of enteric bladder augmentations: the risk for malignancy.
      ,
      • Husmann D.A.
      • Fox J.
      • Higuchi T.
      Malignancy following bladder augmentation recommendations for long-term follow-up and cancer screening.
      ]. Specifically, 4% (8/203) of patients who were followed for ≥10 years developed a bladder tumor. The median age at the time of tumor diagnosis was 51 years (range 30–64). Median time from augmentation to tumor development was 39 years (range 22–53). In the patients who developed a tumor, 75% (6/8) had an adenocarcinoma, and 25% (2/8) developed an urothelial tumor. Median stage of the tumor at the time of diagnosis was 4 (range 2–4). Cancer-specific deaths occurred in 75% (6/8) of the patients, with a median survival of 15 months (range 6–36). In essence, cancer-specific deaths took place in 1.6% (6/385) of the patients (Table 2). When patients who had undergone a bladder augmentation were compared to an age-matched control population with a similar primary congenital bladder abnormality managed with anticholinergics and intermittent catheterization, an increase in the risk of bladder malignancy following an ileal or colonic bladder augment could not be found, and 2.5% (5/203) of the non-augmented patients developed a bladder tumor (P = 0.397) [
      • Higuchi T.T.
      • Granberg C.F.
      • Fox J.A.
      • Husmann D.A.
      Augmentation cystoplasty and risk of neoplasia: fact, fiction and controversy.
      ,
      • Husmann D.A.
      • Fox J.
      • Higuchi T.
      Malignancy following bladder augmentation recommendations for long-term follow-up and cancer screening.
      ]. These findings suggest that it is the primary bladder dysfunction and/or alterations in the patient's clinical environment, and not the augmentation, that is primarily responsible for the tumor development [
      • Higuchi T.T.
      • Granberg C.F.
      • Fox J.A.
      • Husmann D.A.
      Augmentation cystoplasty and risk of neoplasia: fact, fiction and controversy.
      ,
      • Husmann D.A.
      • Fox J.
      • Higuchi T.
      Malignancy following bladder augmentation recommendations for long-term follow-up and cancer screening.
      ].
      Table 2Characteristics of patients with bladder augmentation who developed a malignancy.
      Patient numberEtiology of bladder dysfunctionAge at diagnosis of cancerYears since augmentation
      Years since augment includes entire time ileal segment exposed to urine.
      Type of augmenting segmentCancer type and TNM stageAJCC stageCancer specific survival
      1Spina bifida
      History of ileal conduit with conduit incorporated into augmentation.
      6152IleumUrothelial (pT2, N0, M0)2NED: 96 months
      2Spina bifida
      History of ileal conduit with conduit incorporated into augmentation.
      6453IleumUrothelial (pT2, N0, M0)2NED: 144 months
      3PUV renal transplant4325IleumAdenocarcinoma (pT3, N2, M0)4DOD: 12 months
      4PUV renal transplant3422ColonAdenocarcinoma (pT3, N1, M0)4DOD: 24 months
      5Exstrophy
      History of ileal conduit with conduit incorporated into augmentation.
      5132ColonAdenocarcinoma (pT3, N2, M0)4DOD: 36 months
      6Exstrophy5247IleumAdenocarcinoma (pT3, N2, M0)4DOD: 18 months
      7Exstrophy3022IleumAdenocarcinoma (pT4, N2, M1)4DOD: 6 months
      8Exstrophy
      History of ileal conduit with conduit incorporated into augmentation.
      6152Ileum and colonAdenocarcinoma (pT3, N1, M0)4DOD: 12 months
      AJCC, American Joint Committee on Cancer; NED, no evidence of disease; DOD, died of disease; PUV, posterior urethral valves; T, tumor stage; N, nodal metastasis; M, distal metastasis.
      a History of ileal conduit with conduit incorporated into augmentation.
      b Years since augment includes entire time ileal segment exposed to urine.
      The development of a malignant tumor within a urinary reservoir or augmented bladder is based on the type of bowel used, the length of time from surgery, the concurrent use of immunosuppressives, a history of viral cystitis, and is related to the primary etiology for primary bladder dysfunction [
      • Higuchi T.T.
      • Granberg C.F.
      • Fox J.A.
      • Husmann D.A.
      Augmentation cystoplasty and risk of neoplasia: fact, fiction and controversy.
      ,
      • Husmann D.A.
      • Fox J.
      • Higuchi T.
      Malignancy following bladder augmentation recommendations for long-term follow-up and cancer screening.
      ,
      • Woodhouse C.
      • North A.
      • Gearhart J.
      Standing the test of time: long-term outcome of reconstruction of the exstrophy bladder.
      ]. Studies have shown that two distinct patient populations appear to be at an increased risk of tumor development following a bladder augmentation; specifically, patients that have undergone a gastric augment and those with an augmentation that are on immunosuppressives [
      • Higuchi T.T.
      • Fox J.A.
      • Husmann D.A.
      Annual endoscopy and urine cytology for the surveillance of bladder tumors after enterocystoplasty for congenital bladder anomalies.
      ,
      • Husmann D.A.
      • Rathbun S.R.
      Long-term follow-up of enteric bladder augmentations: the risk for malignancy.
      ,
      • Husmann D.A.
      • Fox J.
      • Higuchi T.
      Malignancy following bladder augmentation recommendations for long-term follow-up and cancer screening.
      ,
      • Husmann D.A.
      Malignancy after gastrointestinal augmentation.
      ]. Both of these patient populations appear to have a 2–3 fold increased risk of cancer development compared to those with a primary congenital bladder dysfunction managed by anticholinergics and intermittent catheterization [
      • Hamid R.
      • Greenwell T.
      • Nethercliffe J.M.
      • Freeman A.
      • Venn S.N.
      • Woodhouse C.R.
      Routine surveillance cystoscopy for patients with augmentation and substitution cystoplasty for benign urological conditions. Is it necessary.
      ,
      • Husmann D.A.
      • Rathbun S.R.
      Long-term follow-up of enteric bladder augmentations: the risk for malignancy.
      ,
      • Husmann D.A.
      • Fox J.
      • Higuchi T.
      Malignancy following bladder augmentation recommendations for long-term follow-up and cancer screening.
      ,
      • Husmann D.A.
      Malignancy after gastrointestinal augmentation.
      ].
      The question that arises is: should patients with a congenital bladder dysfunction treated by bladder augmentation be routinely screened by annual endoscopy and cytology? It is believed that data to support this recommendation do not exist [
      • Husmann D.
      Long-term complications following bladder augmentations in patients with spina bifida; bladder calculi, perforation of the augmented bladder and upper tract deterioration.
      ]. Specifically, the World Health Organization recommends annual cancer screening be performed when the four following criteria are met: 1) cancer has a high prevalence in a well-defined patient population; 2) cancer routinely presents at a low treatable stage; 3) screening tests are available that are safe, inexpensive, reliable and reproducible with high specificity and sensitivity; 4) the screening test must allow cancer to be diagnosed at a low treatable stage and result in an improved patient prognosis [
      • Higuchi T.T.
      • Fox J.A.
      • Husmann D.A.
      Annual endoscopy and urine cytology for the surveillance of bladder tumors after enterocystoplasty for congenital bladder anomalies.
      ,
      • Husmann D.A.
      • Fox J.
      • Higuchi T.
      Malignancy following bladder augmentation recommendations for long-term follow-up and cancer screening.
      ].
      Currently, epidemiological and pathological findings reveal that tumors arising within a congenitally dysfunctional bladder cannot meet these criteria. Specifically, there is a low risk of malignancy, approximately 1.5% per decade, with 75% of patients presenting with locally advanced disease or nodal metastasis at the time of diagnosis. These tumors are highly aggressive, with a cancer-specific mortality of 75% at 15 months following the diagnosis [
      • Higuchi T.T.
      • Granberg C.F.
      • Fox J.A.
      • Husmann D.A.
      Augmentation cystoplasty and risk of neoplasia: fact, fiction and controversy.
      ,
      • Higuchi T.T.
      • Fox J.A.
      • Husmann D.A.
      Annual endoscopy and urine cytology for the surveillance of bladder tumors after enterocystoplasty for congenital bladder anomalies.
      ,
      • Husmann D.A.
      • Fox J.
      • Higuchi T.
      Malignancy following bladder augmentation recommendations for long-term follow-up and cancer screening.
      ]. Due to the rapid growth of these highly invasive tumors, routine yearly cystoscopy appears to be unable to diagnose low-stage curable disease [
      • Higuchi T.T.
      • Fox J.A.
      • Husmann D.A.
      Annual endoscopy and urine cytology for the surveillance of bladder tumors after enterocystoplasty for congenital bladder anomalies.
      ]. In support of this statement are five case reports where patients were noted to have a normal cystoscopic evaluation of their bladder augmentation, 4–18 months before the diagnosis of an invasive bladder tumor. All five patients eventually succumbed to their tumor [
      • Higuchi T.T.
      • Fox J.A.
      • Husmann D.A.
      Annual endoscopy and urine cytology for the surveillance of bladder tumors after enterocystoplasty for congenital bladder anomalies.
      ].
      In essence, low-stage medically or surgically curative bladder cancer can rarely be detected by annual screening endoscopic evaluations [
      • Higuchi T.T.
      • Fox J.A.
      • Husmann D.A.
      Annual endoscopy and urine cytology for the surveillance of bladder tumors after enterocystoplasty for congenital bladder anomalies.
      ,
      • Husmann D.A.
      • Fox J.
      • Higuchi T.
      Malignancy following bladder augmentation recommendations for long-term follow-up and cancer screening.
      ,
      • Hamid R.
      • Greenwell T.
      • Nethercliffe J.M.
      • Freeman A.
      • Venn S.N.
      • Woodhouse C.R.
      Routine surveillance cystoscopy for patients with augmentation and substitution cystoplasty for benign urological conditions. Is it necessary.
      ]. Indeed, it is believed that the costs of annual endoscopic studies is not merited, due to the low prevalence of the disease and its inability to diagnose early stage, curable tumors [
      • Higuchi T.T.
      • Granberg C.F.
      • Fox J.A.
      • Husmann D.A.
      Augmentation cystoplasty and risk of neoplasia: fact, fiction and controversy.
      ,
      • Higuchi T.T.
      • Fox J.A.
      • Husmann D.A.
      Annual endoscopy and urine cytology for the surveillance of bladder tumors after enterocystoplasty for congenital bladder anomalies.
      ,
      • Husmann D.A.
      • Fox J.
      • Higuchi T.
      Malignancy following bladder augmentation recommendations for long-term follow-up and cancer screening.
      ,
      • Hamid R.
      • Greenwell T.
      • Nethercliffe J.M.
      • Freeman A.
      • Venn S.N.
      • Woodhouse C.R.
      Routine surveillance cystoscopy for patients with augmentation and substitution cystoplasty for benign urological conditions. Is it necessary.
      ].

      Chronic renal failure following bladder augmentation and the increased risk of patient death

      One of the primary goals of bladder augmentation is to prevent upper tract deterioration and/or the development of ≥Stage 3 CRF due to high-pressure bladder storage [
      • Husmann D.
      Long-term complications following bladder augmentations in patients with spina bifida; bladder calculi, perforation of the augmented bladder and upper tract deterioration.
      ]. Specifically, the goal is to avoid the 20% increased risk of cardiovascular death that is associated with ≥Stage 3 CRF [
      • Husmann D.
      Long-term complications following bladder augmentations in patients with spina bifida; bladder calculi, perforation of the augmented bladder and upper tract deterioration.
      ,
      • Go A.
      • Chertow G.
      • Fan D.
      • et al.
      Chronic kidney disease and the risks of cardiovascular events and hospitalization.
      ].
      To date, 15% (58/385) of the present patients with bladder augmentation have developed ≥Stage 3 CRF, with 1% (4/385) dying as a complication of CRF or renal transplantation. Although some authors have speculated that the onset of renal failure in patients undergoing a bladder augmentation is primarily a consequence of pre-existing renal injury and not the result of the bladder augmentation, it is concerning that individuals who undergo a bladder augmentation can be plagued with problems that may pre-dispose to CRF [
      • Schlomer B.J.
      • Copp H.L.
      Cumulative incidence of outcomes and urologic procedures after augmentation cystoplasty.
      ,
      • Husmann D.
      Long-term complications following bladder augmentations in patients with spina bifida; bladder calculi, perforation of the augmented bladder and upper tract deterioration.
      ,
      • Muller T.
      • Arbeiter K.
      • Aufricht C.
      Renal function in meningomyelocele: risk factors, chronic renal failure, renal replacement therapy and transplantation.
      ,
      • DeFoor W.
      • Heshmat S.
      • Minevich E.
      • Reddy P.
      • Koyle M.
      • Sheldon C.
      Long-term outcomes of the neobladder in pediatric continent urinary diversion.
      ]. Specifically, non-compliance with intermittent catheterization will, from experience, place the patient at a high risk for the development of CRF [
      • Schlomer B.J.
      • Copp H.L.
      Cumulative incidence of outcomes and urologic procedures after augmentation cystoplasty.
      ,
      • Husmann D.
      Long-term complications following bladder augmentations in patients with spina bifida; bladder calculi, perforation of the augmented bladder and upper tract deterioration.
      ,
      • Higuchi T.T.
      • Fox J.A.
      • Husmann D.A.
      Annual endoscopy and urine cytology for the surveillance of bladder tumors after enterocystoplasty for congenital bladder anomalies.
      ,
      • DeFoor W.
      • Heshmat S.
      • Minevich E.
      • Reddy P.
      • Koyle M.
      • Sheldon C.
      Long-term outcomes of the neobladder in pediatric continent urinary diversion.
      ].
      The question that arises is how well do bladder augmentations preserve renal function? In this regard, the present study evaluated two dichotomous patient categories: individuals undergoing bladder augmentation with a simultaneous bladder outlet procedure and continent abdominal stoma versus patients with a bladder augmentation that are catheterizing per urethra. Comparison between these two different patient populations is imperative, due to the reportedly 2–5 fold increased risk of complications in patients undergoing a bladder neck procedure, augmentation and continent abdominal stoma compared to individuals with a bladder augmentation catheterizing through the urethra [
      • Husmann D.
      Long-term complications following bladder augmentations in patients with spina bifida; bladder calculi, perforation of the augmented bladder and upper tract deterioration.
      ,
      • Metcalfe P.
      • Cain M.
      • Kaefer M.
      • Gilley D.A.
      • Meldrum K.K.
      • Misseri R.
      • et al.
      What is the need for additional bladder surgery after bladder augmentation in childhood.
      ,
      • Gerharz W.
      • Turner W.
      • Kalbe T.
      • Woodhouse C.
      Metabolic and functional consequences of urinary reconstructing with bowel.
      ,
      • Biers S.
      • Venn S.
      • Greenwell T.
      The past, present and future of augmentation cystoplasty.
      ]. The present study limited the population to include only persons who had no evidence of renal scarring, as determined by renal ultrasonography, and normal renal clearance values (GFR ≥90 ml/min/1.73 m2) when they were first evaluated in the transitional clinic. Also, all patients had to have a minimum follow-up interval of 10 years since their augmentation. A total of 45% (173/385) of patients met these two criteria.
      The comparison of how well these two different types of surgical procedures have preserved renal function is depicted in Table 3. Perhaps the most telling factor regarding why renal scarring developed following referral to the transitional clinic was the finding that 67% (39/58) of patients who developed new onset of renal scarring did so after they were documented to be non-compliant with intermittent catheterization. It is intriguing to find that the percentage of patients who developed renal scarring and/or CRF was significantly higher in those catheterizing per urethra compared with through an abdominal stoma (see Table 3). It is noteworthy that >80% of the patients in both categories had their mobility as an adult confined to a wheelchair. Both patient populations were associated with a high incidence of obesity, BMI ≥30, which was approximately 40% of both patient groups: 41%, 16/39 and 39%, 54/134, respectively. Moribund obesity BMI >40 was noted in 8% of both groups: 8%, 3/39 and 8%, 11/134, respectively.
      Table 3Comparison of renal deterioration following bladder augmentation with and without bladder neck reconstruction and creation of a continent abdominal stoma.
      Patient categories% of patients with renal scaring or loss of one kidney% of patients with renal scarring and a history of non-compliance with catheterization
      Non-compliance with catheterization was defined as a ≥3 month period where the individual admitted to catheterizing three times or fewer per day.
      % of patients with ≥Stage 3 chronic renal failureMedian length of follow-up since augmentation (range)
      Bladder augmentation with bladder neck reconstruction or sling catheterization via continent stoma n = 13431% (41/134)56% (24/41)11% (15/134)14 years (10–45)
      Bladder augmentation without bladder neck reconstruction catheterization through urethra n = 3943% (17/39)88% (15/17)36% (14/39)15 years (10–38)
      Statistical evaluation P=0.1300.028<0.001
      a Non-compliance with catheterization was defined as a ≥3 month period where the individual admitted to catheterizing three times or fewer per day.
      By reviewing the data and the existing literature, it was hypothesized that the degree of non-compliance with intermittent catheterization may be impacted by both mental deficiency and obesity. Specifically, it has been documented that spina bifida patients with mental deficiency are more likely to become obese and subsequently develop impaired mobility as they age [
      • Crytzer T.
      • Dicianno B.
      • Kapoor R.
      Physical activity, exercise and health-related measures of fitness in adults with spina bifida: a review of the literature.
      ,
      • Webb T.
      Optimizing health care for adults with spina bifida.
      ]. It is interesting to note that, within the present patient population, obese patients were more likely to be compliant with intermittent catheterization schedules when an abdominal stoma was present compared with obese patients catheterizing through the urethra: 78% (50/64) vs 37% (7/19), respectively, P = 0.0008 (Table 4). Similarly, obese patients catheterizing via an abdominal stoma were significantly less likely to develop CRF than those catheterizing per urethra 16% (10/64) vs 63% (12/19), P = 0.0003 (Table 4). Indeed, it is believed that the presence of obesity makes management of the spina bifida patient by a continent stoma both attractive and problematic [
      • Husmann D.
      Long-term complications following bladder augmentations in patients with spina bifida; bladder calculi, perforation of the augmented bladder and upper tract deterioration.
      ,
      • Fox J.A.
      • Husmann D.A.
      Continent urinary diversion in childhood: complications of alcohol abuse developing in adulthood.
      ]. Attractive because the abdominal stoma makes the catheterization easier to perform when the obese patient is seated in a wheelchair. Problematic in that obesity has been found to be significantly associated with increased complications of the catheterizable stoma, for example: stomal stenosis, stomal retraction, and difficulty with catheterization [
      • Katkorri D.
      • Samavedi S.
      • Kava B.
      • Soloway M.S.
      • Manohararn M.
      Synchronous panniculectomy with stomal revision for obese patients with stomal stenosis and stomal retraction.
      ].
      Table 4Impact of obesity on compliance with intermittent catheterization and onset of chronic renal failure in patients with and without a continent abdominal stoma.
      Patient categories% of patients with renal scarring or loss of one kidney% of patients that were compliant with catheterization
      Non-compliance with catheterization was defined as a ≥3 month period where the individual admitted to catheterizing three times or fewer per day.
      % of patients with ≥Stage 3 chronic renal failure
      Bladder augmentation with bladder neck reconstruction or sling catheterization via continent stoma BMI ≥30 n = 6445% (23/64)78% (50/64)16% (10/64)
      Bladder augmentation with bladder neck reconstruction or sling catheterization via continent stoma BMI <30 n = 7017% (18/70)86% (60/70)7% (5/70)
      Statistical evaluation, P=0.19950.25240.1198
      Bladder augmentation without bladder neck reconstruction catheterization through the urethra BMI ≥30 n = 1968% (13/19)37% (7/19)63% (12/19)
      Bladder augmentation without bladder neck reconstruction catheterization through urethra BMI <30 n = 2020% (4/20)85% (17/20)10% (2/20)
      Statistical evaluation, P=0.0020.0030.008
      a Non-compliance with catheterization was defined as a ≥3 month period where the individual admitted to catheterizing three times or fewer per day.

      The impact of obesity, mental deficiency, and patient non-compliance on mortality following bladder augmentation

      The pediatric urologist contemplating performing a bladder augmentation must realize that there is a progressive increase in the incidence of obesity that occurs in the spina bifida patient population with aging. Notably, the incidence of obesity in the adult spina bifida population is four-fold higher than in childhood (<10 years of age), and two-fold greater than that found in adolescence (≥10–19 years) [
      • Crytzer T.
      • Dicianno B.
      • Kapoor R.
      Physical activity, exercise and health-related measures of fitness in adults with spina bifida: a review of the literature.
      ,
      • Webb T.
      Optimizing health care for adults with spina bifida.
      ]. This incidence of obesity, as previously noted, is significantly increased by the presence of mental impairment and associated with further limiting mobility [
      • Crytzer T.
      • Dicianno B.
      • Kapoor R.
      Physical activity, exercise and health-related measures of fitness in adults with spina bifida: a review of the literature.
      ,
      • Webb T.
      Optimizing health care for adults with spina bifida.
      ]. These facts need to be viewed in the context that the median age of bladder augmentation within the United States is at 9 years, a detail that reflects that the majority of obese patients will develop their obesity following urologic reconstruction [
      • Husmann D.
      Long-term complications following bladder augmentations in patients with spina bifida; bladder calculi, perforation of the augmented bladder and upper tract deterioration.
      ,
      • Schlomer B.
      • Saperston K.
      • Baskin L.
      National trends in augmentation cystoplasty in the 2000's and factors associated with patient outcomes.
      ,
      • Lendvay T.
      • Cowan C.
      • Mitchell M.
      • Joyner B.D.
      • Grady R.W.
      Augmentation cystoplasty rates at children's hospitals in the United States: a pediatric health information system database study.
      ]. The interplay between obesity, hypertension, hyperlipidemia, diabetes mellitus, nephrolithiasis, compliance with urethral catheterization and an increase in the complications related to a continent abdominal stoma must not be understated. Furthermore, the relationship of these co-morbidities to the onset of CRF should not be minimalized. Indeed, it is believed that the early involvement of dietary consultants and the establishment of a well-balanced diet and weight management are critical in the successful long-term management of this patient population [
      • Husmann D.
      Long-term complications following bladder augmentations in patients with spina bifida; bladder calculi, perforation of the augmented bladder and upper tract deterioration.
      ,
      • Crytzer T.
      • Dicianno B.
      • Kapoor R.
      Physical activity, exercise and health-related measures of fitness in adults with spina bifida: a review of the literature.
      ,
      • Katkorri D.
      • Samavedi S.
      • Kava B.
      • Soloway M.S.
      • Manohararn M.
      Synchronous panniculectomy with stomal revision for obese patients with stomal stenosis and stomal retraction.
      ,
      • Keddis M.T.
      • Rule A.D.
      Nephrolithiasis and loss of kidney function.
      ].

      Conclusion

      This study found that assessment of the individual's intellectual and physical capability to comply with medical directives, refrain from high-risk habits, ability to follow a nutritional diet plan, maintain a healthy weight and continue with long-term follow-up visits are critical to the enduring success of a bladder augmentation [
      • Husmann D.
      Long-term complications following bladder augmentations in patients with spina bifida; bladder calculi, perforation of the augmented bladder and upper tract deterioration.
      ,
      • Fox J.A.
      • Husmann D.A.
      Continent urinary diversion in childhood: complications of alcohol abuse developing in adulthood.
      ].

      Funding

      None.

      Conflict of interest

      None.

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