Morphological Changes on the Intestinal Mucosa in Orthotopic Neobladder

Tonno, F. Di; Siracusano, Salvatore; Ciciliato, Stefano; Visalli, Francesco; Lampropoulou, N.; Lavelli, D.

doi:10.1159/000338168

Cited by 12 publications

(5 citation statements)

References 32 publications

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“…The ureters are connected to this reservoir, which in turn is reconnected to the urethra to allow patients to urinate normally (Freeman et al 1996;Stein et al 2005;Hautmann et al 2007). The autologous transposition of the small intestine to form a neobladder marks the precise time point when the tissue becomes exposed to a foreign bladder environment in which low intraluminal pH and various urinary solutes trigger pathophysiological changes in the otherwise normal intestinal mucosa (Philipson et al 1987;Aragona et al 1998;Gatti et al 1999;Di Tonno et al 2012). The neobladder, however, maintains the blood supply of the original tissue so that the predominant change of the local tissue environment is in the content of the lumen to which the intestinal cells are exposed.…”

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confidence: 99%

Reprogramming of the human intestinal epigenome by surgical tissue transposition

et al. 2014

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Extracellular cues play critical roles in the establishment of the epigenome during development and may also contribute to epigenetic perturbations found in disease states. The direct role of the local tissue environment on the post-development human epigenome, however, remains unclear due to limitations in studies of human subjects. Here, we use an isogenic human ileal neobladder surgical model and compare global DNA methylation levels of intestinal epithelial cells pre-and post-neobladder construction using the Infinium HumanMethylation450 BeadChip. Our study is the first to quantify the effect of environmental cues on the human epigenome and show that the local tissue environment directly modulates DNA methylation patterns in normal differentiated cells in vivo. In the neobladder, the intestinal epithelial cells lose their tissue-specific epigenetic landscape in a time-dependent manner following the tissue's exposure to a bladder environment. We find that de novo methylation of many intestine-specific enhancers occurs at the rate of 0.41% per month (P < 0.01, Pearson = 0.71), while demethylation of primarily non-intestine-specific transcribed regions occurs at the rate of -0.37% per month (P < 0.01, Pearson = -0.57). The dynamic resetting of the DNA methylome in the neobladder not only implicates local environmental cues in the shaping and maintenance of the epigenome but also illustrates an unexpected cross-talk between the epigenome and the cellular environment.

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confidence: 99%

Reprogramming of the human intestinal epigenome by surgical tissue transposition

et al. 2014

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“…Changes to the novel urinary microenvironment have been hypothesised to promote this gradual stabilisation of renal function in ONB recipients. Previous studies have shown that prolonged contact with urine likely induces progressive blunting of microvilli throughout the neobladder intestinal segment [12,13]. Such morphological changes in the neobladder mucosa better approximate the uroepithelium, thus reducing the absorptive surface area for electrolyte exchange, resulting in decreased long‐term risk of metabolic acidosis due to ileal absorption of urinary ammonium.…”

Section: Discussionmentioning

confidence: 99%

Long‐term renal function in patients with chronic kidney disease following radical cystectomy and orthotopic neobladder

et al. 2022

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To evaluate long-term renal function in patients with chronic kidney disease (CKD) Stage IIIa who underwent radical cystectomy and orthotopic neobladder (RC/ONB) compared to matched controls. Patients and MethodsUsing our Institutional Review Board-approved institutional database, patients with a glomerular filtration rate (GFR) of 45-59.9 mL/min/1.73 m 2 who underwent RC/ONB were identified. A control group of patients with a GFR of ≥60 mL/min/1.73 m 2 was selected. Groups were matched based on age, baseline hypertension/diabetes mellitus, perioperative chemotherapy, and preoperative hydronephrosis. A decrease in GFR of >10 mL/min/1.73 m 2 during the follow-up was considered significant. A multivariate Cox regression analysis was performed to identify predictors of GFR decline in each group. ResultsOf 1237 patients who underwent RC/ONB, 508 patients were included (254 per group). The mean preoperative GFR was 53.3 mL/min/1.73 m 2 in the study group and 78.8 mL/min/1.73 m 2 in controls. The median follow-up was 3.7 years. During follow-up, GFR stayed at or above baseline in 51% of the study patients compared to 46% of the controls (P = 0.5). The mean time to a significant GFR decline in the study patients was significantly longer compared to the controls (5.6 vs 2 years, respectively; P < 0.001). In multivariate analysis, neoadjuvant chemotherapy was found to be the strongest predictor of a significant GFR decline as well as GFR decline below baseline (hazard ratio [HR] 2.15, 95% confidence interval [CI] 1.4-3.29, P = 0.004; and HR 2.15, 95% CI 1.4-3.29, P < 0.001, respectively). ConclusionPatients with CKD Stage IIIa who undergo ONB appear to have comparable long-term renal function to those with a GFR of ≥60 mL/min/1.73 m 2 . An ONB reconstruction is a safe option for patients with CKD Stage IIIa desiring a continent diversion.

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“…However, after 3-6 months after surgery, atrophic changes in the intestinal mucosa lining the neobladder occur, and consequently, the neobladder is less susceptible to bacterial colonization and infection. 20,21 Finally, prolonged urinary catheterization is related to UTI. For these mechanisms, it can be suggested that UTI rate in patients with ONB decreases overtime especially after 3 months postoperatively.…”

Section: Discussionmentioning

confidence: 99%

Febrile Urinary Tract Infection after Radical Cystectomy with Urinary Diversion: Different Characteristics in Patients with Ileal Conduit and Orthotopic Neobladder

Lee¹,

Baek²,

Song³

et al. 2020

J Men's Health

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Background and ObjectiveTo compare the incidence of febrile urinary tract infection (UTI) and bacterial identification between patients with orthotopic neobladder (ONB) and ileal conduit (IC). Materials and MethodsData of 164 patients who underwent radical cystectomy with ONB and IC for bladder cancer between January 2009 and January 2018 at our institution were analyzed. Febrile UTI observed was listed and subsequently compared. Incidence of febrile UTI, clinicopathological characteristics, and microorganisms identified were reported at 3 months interval; and preoperative predictors of febrile UTI were evaluated with Cox regression analysis. Patients were divided into ONB and IC. ResultsThe study cohort included 52 patients with ONB and 112 patients with IC. Febrile UTI was diagnosed in 49 (29.9%) patients. Compared to IC group, ONB group had significantly higher incidence of young age (p=0.00), lower cancer stage (p=0.013), longer hospital stay (p=0.049), longer operation time (p=0.00), and higher incidence of febrile UTI within the first 3 months after surgery (p=0.006). On univariable and multivariable analysis, factors associated with significantly increased febrile UTI risk were diabetes (odds ratio [OR]: 4.52; p=0.002) and ONB diversion (OR: 1.27; p=0.031). Forty-four (89.8%) patients were culture positive. However, significant difference in microorganisms was not detected between patients who under-went ONB or IC diversion. ConclusionDiabetes and ONB diversion were associated with higher risk symptomatic UTI following radical cystectomy.

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Morphological Changes on the Intestinal Mucosa in Orthotopic Neobladder

Cited by 12 publications

References 32 publications

Reprogramming of the human intestinal epigenome by surgical tissue transposition

Reprogramming of the human intestinal epigenome by surgical tissue transposition

Long‐term renal function in patients with chronic kidney disease following radical cystectomy and orthotopic neobladder

Febrile Urinary Tract Infection after Radical Cystectomy with Urinary Diversion: Different Characteristics in Patients with Ileal Conduit and Orthotopic Neobladder

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