TOpic: rare and special cases, the real "Strange cases"

Introduction: The bladder hernia represents approximately 1-3% of all inguinal hernias, where patients aged more than 50 years have a higher incidence (10%). Many factors contribute to the development of a bladder hernia, including the presence of a urinary outlet obstruction causing chronic bladder distention, the loss of bladder tone, pericystitis, the perivesical bladder fat protrusion and the obesity

Spine immobilization apparatus

The apparatus makes use of a normally flat, flexible bladder filled with beads or micro-balloons that form a rigid mass when the pressure within the bladder is decreased below ambient through the use of a suction pump so that the bladder can be conformed to the torso of the victim and provide the desired restraint. The bladder is strapped to the victim prior to being rigidified by an arrangement of straps which avoid the stomach area. The bladder is adapted to be secured to a rigid support, i.e., a rescue chair, so as to enable removal of a victim after the bladder has been made rigid. A double sealing connector is used to connect the bladder to the suction pump and a control valve is employed to vary the pressure within the bladder so as to soften and harden the bladder as desired

Effect of high level of bladder filling on spinal nociception and motoneuronal excitability

To verify whether high level of bladder distension may counteract the inhibitory effect of descending pathways on sacral spinal cord neurons and to investigate which spinal circuitries are possibly involved in such a viscero-somatic interaction. Nociceptive withdrawal reflex (NWR), cutaneous silent period (CSP), and H-reflex were recorded in both lower and upper limbs of twenty-eight healthy subjects. Subjects were examined during baseline (empty bladder, no voiding desire), high level of bladder filling (urgency desire), and control (empty bladder, no voiding desire) sessions. Results showed that the NWR and its related pain perception were reduced in the upper limbs, while only a pain perception reduction in males was observed in the lower limbs. The H-reflex was inhibited in both limbs. No effects were found on the CSP duration. The decrease in both the NWR and its related pain perception in the upper limbs confirms the presence of a bladder distension-induced descending inhibitory modulation on nociception at spinal level. The lack of a similar inhibitory effect in the lower limbs suggests that excitatory nociceptive inputs from bladder afferents counterbalance the inhibitory effect on sacral spinal cord. The lack of the descending inhibitory effect may be a mechanism aimed at forcing the micturition phase to avoid bladder damage caused by bladder sovradistension

Impacts of chronic stress on urinary bladder function & recovery through modification of PACAP signaling

Stress can cause or contribute to bladder dysfunction though specific effects remain unclear. Individuals with interstitial cystitis (IC)/bladder pain syndrome (BPS) experience increased symptom severity with stress, including pain and increased urgency and frequency of voiding. Further research can identify stress-related changes to urinary mechanisms, such as changes in sensory neurotransmitters and subsequent receptor expression. These factors could then become targets for future therapies providing bladder dysfunction relief. Alterations in PACAP and TRPV channel expression have been shown in sensory pathways in response to disease. My research studied the effects of chronic stress on bladder function and the potential for PACAP(6-38), a PACAP antagonist, to recover normal function. Mice went through a repeated variate stress regime followed by bladder tube implant and cystometrogram recording. Bladder, dorsal root ganglia (DRG), and spinal cord tissues were collected and immunostained for the presence of TRPV1, TRPV4, and PACAP expression. Chronic stress decreased inter-contraction interval (ICI) and bladder capacity while increasing bladder pressures. Both control and stressed male and female mice showed improvement following a 30-minute intravesical infusion of PACAP(6-38), with ICI and bladder capacity measures having the most consistent improvement across groups. PACAP and TRPV1 expression was upregulated in the bladder afferent pathway. These findings suggest that chronic stress can contribute to bladder dysfunction, and it seems to be mediated in part by upregulation of PACAP and TRPV channel activity. With further research, these factors may be valid molecular targets for therapy. As chronic stress may present alone or in combination with other conditions (IC/BPS, injury, etc.), it is critical to understand stress-related changes in order to reduce or eliminate their impact

Methionine Adenosyltransferase 1a (MAT1A) Enhances Cell Survival During Chemotherapy Treatment and is Associated with Drug Resistance in Bladder Cancer PDX Mice.

Bladder cancer is among the top ten most common cancers, with about ~380,000 new cases and ~150,000 deaths per year worldwide. Tumor relapse following chemotherapy treatment has long been a significant challenge towards completely curing cancer. We have utilized a patient-derived bladder cancer xenograft (PDX) platform to characterize molecular mechanisms that contribute to relapse following drug treatment in advanced bladder cancer. Transcriptomic profiling of bladder cancer xenograft tumors by RNA-sequencing analysis, before and after relapse, following a 21-day cisplatin/gemcitabine drug treatment regimen identified methionine adenosyltransferase 1a (MAT1A) as one of the significantly upregulated genes following drug treatment. Survey of patient tumor sections confirmed elevated levels of MAT1A in individuals who received chemotherapy. Overexpression of MAT1A in 5637 bladder cancer cells increased tolerance to gemcitabine and stalled cell proliferation rates, suggesting MAT1A upregulation as a potential mechanism by which bladder cancer cells persist in a quiescent state to evade chemotherapy

Functional Genomics Profiling of Bladder Urothelial Carcinoma MicroRNAome as a Potential Biomarker.

Though bladder urothelial carcinoma is the most common form of bladder cancer, advances in its diagnosis and treatment have been modest in the past few decades. To evaluate miRNAs as putative disease markers for bladder urothelial carcinoma, this study develops a process to identify dysregulated miRNAs in cancer patients and potentially stratify patients based on the association of their microRNAome phenotype to genomic alterations. Using RNA sequencing data for 409 patients from the Cancer Genome Atlas, we examined miRNA differential expression between cancer and normal tissues and associated differentially expressed miRNAs with patient survival and clinical variables. We then correlated miRNA expressions with genomic alterations using the Wilcoxon test and REVEALER. We found a panel of six miRNAs dysregulated in bladder cancer and exhibited correlations to patient survival. We also performed differential expression analysis and clinical variable correlations to identify miRNAs associated with tobacco smoking, the most important risk factor for bladder cancer. Two miRNAs, miR-323a and miR-431, were differentially expressed in smoking patients compared to nonsmoking patients and were associated with primary tumor size. Functional studies of these miRNAs and the genomic features we identified for potential stratification may reveal underlying mechanisms of bladder cancer carcinogenesis and further diagnosis and treatment methods for urothelial bladder carcinoma

Diabetes-induced alterations in urothelium function:Enhanced ATP release and nerve-evoked contractions in the streptozotocin rat bladder

Up to 80% of patients with diabetes mellitus develop lower urinary tract complications, most commonly diabetic bladder dysfunction (DBD). The aim of this study was to investigate the impact of diabetes on the function of the inner bladder lining (urothelium). Bladder compliance and intraluminal release of urothelial mediators, adenosine triphosphate (ATP) and acetylcholine (ACh) in response to distension were investigated in whole bladders isolated from 2‐ and 12‐week streptozotocin (STZ)‐diabetic rats. Intact and urothelium‐denuded bladder strips were used to assess the influence of the urothelium on bladder contractility. Intraluminal ATP release was significantly enhanced at 2 weeks of diabetes, although not at 12 weeks. In contrast, intraluminal ACh release was unaltered by diabetes. Bladder compliance was also significantly enhanced at both 2 and 12 weeks of diabetes, with greatly reduced intravesical pressures in response to distension. Nerve‐evoked contractions of bladder strips were significantly greater at 2 weeks of diabetes. When the urothelium was absent, nerve‐evoked contractions were reduced, but contractions remained significantly elevated at lower frequencies of stimulation (<5 Hz) in diabetics. Interestingly, although relaxations of bladder strips to isoprenaline were unaltered by diabetes, removal of the urothelium unmasked significantly enhanced relaxations in strips from 2‐ and 12‐week diabetic animals. In conclusion, diabetes alters urothelial function. Enhanced urothelial ATP release may be involved in the hypercontractility observed at early time points of diabetes. These alterations are time‐dependent and may contribute to the mechanisms at play during the development of diabetic bladder dysfunction.Full Tex

A microangiographic study of the effect of hyperthermia on the rabbit bladder

A model was used to study the effect of hyperthermia on a normal tissue. The model selected was the rabbit bladder and the end point measured was the changes in the micro-vasculature of the bladder wall. It was already demonstrated clinically that hot water bladder infusions produce regression in bladder tumors

Long-Term Experience of Chemoradiotherapy Combined with Deep Regional Hyperthermia for Organ Preservation in High-Risk Bladder Cancer (Ta, Tis, T1, T2).

BackgroundThe aim of this study was to evaluate the efficacy and safety of chemoradiotherapy (RCT) combined with regional deep hyperthermia (RHT) of high-risk bladder cancer after transurethral resection of bladder tumor (TUR-BT).Materials and methodsBetween 1982 and 2016, 369 patients with pTa, pTis, pT1, and pT2 cN0-1 cM0 bladder cancer were treated with a multimodal treatment after TUR-BT. All patients received radiotherapy (RT) of the bladder and regional lymph nodes. RCT was administered to 215 patients, RCT + RHT was administered to 79 patients, and RT was used in 75 patients. Treatment response was evaluated 4-6 weeks after treatment with TUR-BT.ResultsComplete response (CR) overall was 83% (290/351), and in treatment groups was RT 68% (45/66), RCT 86% (178/208), and RCT + RHT 87% (67/77). CR was significantly improved by concurrent RCT compared with RT (odds ratio [OR], 2.32; 95% confidence interval [CI], 1.05-5.12; p = .037), less influenced by hyperthermia (OR, 2.56; 95% CI, 0.88-8.00; p = .092). Overall survival (OS) after RCT was superior to RT (hazard ratio [HR], 0.7; 95% CI, 0.50-0.99; p = .045). Five-year OS from unadjusted Kaplan-Meier estimates was RCT 64% versus RT 45%. Additional RHT increased 5-year OS to 87% (HR, 0.32; 95% CI, 0.18-0.58; p = .0001). RCT + RHT compared with RCT showed a significantly better bladder-preservation rate (HR, 0.13; 95% CI, 0.03-0.56; p = .006). Median follow-up was 71 months. The median number of RHT sessions was five.ConclusionThe multimodal treatment consisted of a maximal TUR-BT followed by RT; concomitant platinum-based chemotherapy combined with RHT in patients with high-grade bladder cancer improves local control, bladder-preservation rate, and OS. It offers a promising alternative to surgical therapies like radical cystectomy.Implications for practiceRadical cystectomy with appropriate lymph node dissection has long represented the standard of care for muscle-invasive bladder cancer in medically fit patients, despite many centers reporting excellent long-term results for bladder preserving strategies. This retrospective analysis compares different therapeutic modalities in bladder-preservation therapy. The results of this study show that multimodal treatment consisting of maximal transurethral resection of bladder tumor followed by radiotherapy, concomitant platinum-based chemotherapy combined with regional deep hyperthermia in patients with Ta, Tis, T1-2 bladder carcinomas improves local control, bladder-preservation rate, and survival. More importantly, these findings offer a promising alternative to surgical therapies like radical cystectomy. The authors hope that, in the future, closer collaboration between urologists and radiotherapists will further improve treatments and therapies for the benefit of patients

Bladder acellular matrix graft: in vivo functional properties of the regenerated rat bladder.

The purpose of this study was to determine whether the rat urinary bladder augmented by an acellular matrix graft can restore the bladder's low-pressure reservoir function and preserve normal micturition. After partial cystectomy (&gt; 50%) and grafting with the bladder acellular matrix graft (BAMG), storage and voiding functions were monitored in 20 rats by means of a specially designed "micturition cage," leak-point cystography, and cystometry. After 4 months, sections (n = 6) were examined histologically to evaluate regeneration of bladder wall components within the BAMG. Bladder capacity and compliance increased progressively and were significantly higher in the grafted animals than in controls (partial cystectomy only), and volumes per void were significantly higher than in either control or normal animals. At 4 months, the regenerated urothelium, smooth muscle, blood vessels and nerves within the BAMG were qualitatively identical to normal bladder wall. Augmentation cystoplasty with the homologous BAMG leads to morphologic and functional rat bladder regeneration, thus enhancing low-pressure reservoir function and preserving normal micturition