Browsing by Subject "Bladder"

Now showing 1 - 4 of 4
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    Altered sacral neural crest development in Pax3 spina bifida mutants underlies deficits of bladder innervation and function
    (Elsevier, 2021) Deal, Karen K.; Chandrashekar, Anoop S.; Beaman, M. Makenzie; Branch, Meagan C.; Buehler, Dennis P.; Conway, Simon J.; Southard-Smith, E. Michelle; Pediatrics, School of Medicine
    Mouse models of Spina bifida (SB) have been instrumental for identifying genes, developmental processes, and environmental factors that influence neurulation and neural tube closure. Beyond the prominent neural tube defects, other aspects of the nervous system can be affected in SB with significant changes in essential bodily functions such as urination. SB patients frequently experience bladder dysfunction and SB fetuses exhibit reduced density of bladder nerves and smooth muscle although the developmental origins of these deficits have not been determined. The Pax3 Splotch-delayed (Pax3Sp-d) mouse model of SB is one of a very few mouse SB models that survives to late stages of gestation. Through analysis of Pax3Sp-d mutants we sought to define how altered bladder innervation in SB might arise by tracing sacral neural crest (NC) development, pelvic ganglia neuronal differentiation, and assessing bladder nerve fiber density. In Pax3Sp-d/Sp-d fetal mice we observed delayed migration of Sox10+ NC-derived progenitors (NCPs), deficient pelvic ganglia neurogenesis, and reduced density of bladder wall innervation. We further combined NC-specific deletion of Pax3 with the constitutive Pax3Sp-d allele in an effort to generate viable Pax3 mutants to examine later stages of bladder innervation and postnatal bladder function. Neural crest specific deletion of a Pax3 flox allele, using a Sox10-cre driver, in combination with a constitutive Pax3Sp-d mutation produced postnatal viable offspring that exhibited altered bladder function as well as reduced bladder wall innervation and altered connectivity between accessory ganglia at the bladder neck. Combined, the results show that Pax3 plays critical roles within sacral NC that are essential for initiation of neurogenesis and differentiation of autonomic neurons within pelvic ganglia.
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    Invasive poorly differentiated adenocarcinoma of the bladder following augmentation cystoplasty: a multi-institutional clinicopathological study
    (Elsevier, 2021) Anderson, Joshua A.; Matoso, Andres; Murati Amador, Belkiss I.; Cheng, Liang; Stohr, Bradley A.; Chan, Emily; Osunkoya, Adeboye O.; Pathology and Laboratory Medicine, School of Medicine
    Augmentation cystoplasty is a surgical procedure used in the management of patients with neurogenic bladder. This procedure involves anastomosis of the bladder with gastrointestinal grafts, including portions of ileum, colon, or stomach. A rare but important complication of augmentation cystoplasty is the development of malignancy. The majority of malignancies arising in this setting have been described in case reports. A search for cases of non-urothelial carcinoma following augmentation cystoplasty was conducted through the urological pathology files of four major academic institutions. Ten cases were identified, including six cystoprostatectomy/cystectomy, two partial cystectomy, and two transurethral resection of bladder tumour specimens. The mean patient age at diagnosis was 47 years (range 27-87 years). The male:female ratio was 4:6. The tumours tended to present at an advanced stage; four cystoprostatectomy/cystectomy cases were categorised as pT3a, one was categorised as pT3b, and one was categorised as pT4a. Lymph node metastases were present in all cases which had lymph node excision (range 1-16 positive nodes per case). The majority of cases (90%) were predominantly characterised by a poorly differentiated adenocarcinoma with signet ring cell features. Other morphological features included mucinous features (30%), plasmacytoid features (20%), enteric/villous architecture (10%), and large cell undifferentiated morphology (10%). This is the largest study to date on the clinicopathological features of invasive non-urothelial carcinoma of the bladder following augmentation cystoplasty. The tumours are typically poorly differentiated adenocarcinoma, with diffuse signet ring cell features, aggressive, and present at high stage. Further molecular characterisation may provide additional insights into the pathogenesis of this entity.
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    T1 bladder carcinoma with variant histology: pathological features and clinical significance
    (Springer, 2022) Lopez‑Beltran, Antonio; Blanca, Ana; Cimadamore, Alessia; Montironi, Rodolfo; Luque, Rafael J.; Volavšek, Metka; Cheng, Liang; Pathology and Laboratory Medicine, School of Medicine
    The aim of the study was to stratify high-grade T1 (HGT1) bladder urothelial carcinoma into risk categories based on the presence of variant histology when compared to conventional urothelial carcinoma. The clinicopathological features of 104 HGT1 cases of urothelial carcinoma of the bladder with variant histology present in 34 (37%) were assessed. The endpoint of the study was disease-free survival and cancer-specific survival. Overall, variant histology was identified as a significant predictor of disease-free survival (P = 0.035). The presence of any specific variant histology (squamous, glandular, micropapillary, nested, microcystic, inverted growth, villous-like, basaloid, and lymphoepithelioma-like) was identified as a significant predictor of disease-free survival (P = 0.008) and cancer-specific survival (P = 0.0001) in HGT1 bladder cancer. Therefore, our results support including micropapillary HGT1 urothelial carcinoma within the aggressive high-risk category, as suggested by some recent clinical guidelines, but also favor nested, glandular, and basaloid to be placed in the high-risk category due to their potential of aggressive, life-threatening behavior and their limited response to bacillus Calmette-Guerin therapy. Conversely, the low-risk category would include urothelial carcinomas with squamous, inverted growth, or microcystic morphology, all with limited life-threatening potential and good response to current therapy. A very low-risk category would finally include patients whose tumors present villous-like or lymphoepithelioma-like morphology. In conclusion, our findings support the value of reporting the variant histology as a feature of variable aggressiveness in HGT1 urothelial carcinoma of the bladder.
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    Troubleshooting Interstim Sacral Neuromodulation Generators to Recover Function
    (Springer Nature, 2018-08-20) Powell, C.R.; Urology, School of Medicine
    PURPOSE OF REVIEW: Sacral neuromodulation (SNM) is being used to treat lower urinary tract symptoms (LUTS) with growing popularity among clinicians in multiple specialties. As this therapy becomes more common in the USA and Europe, urologists will encounter more patients implanted with SNM generators. RECENT FINDINGS: Over time, it has recently been understood that up to 53% will develop pain at the implant site as reported by Groen et al. (J Urol 186:954, 2011) and 3-38% will lose effective stimulation as reported by Al-zahrani et al. (J Urol 185:981, 2011) and White et al. (Urology 73:731, 2009). There is a paucity of troubleshooting methodology in the literature, apart from revision surgery, to salvage the SNM generator. In fact, it has been suggested that one contemporary series' failure rate is lower than some historic series because of the ability to reprogram devices as reported by Siegel et al. (J Urol 199:229, 2018). Standard algorithms for such reprogramming efforts are lacking in the literature and may salvage some patients otherwise destined for surgical revision or addition of multimodal therapy to achieve acceptable symptom control. It is possible to troubleshoot and thereby salvage many SNM generators, saving patients from surgical revision in many cases and increasing the number of patients with persistent benefit from SNM. The algorithms presented in this manuscript represent a systematic strategy for reprogramming and troubleshooting SNM generators.