Entero-endocrine cells involved in the regulation of digestive function form a large and diverse cell population within the intestinal epithelium of all animals. Together with absorptive enterocytes and secretory gland cells, entero-endocrine cells are generated by the embryonic endoderm and, in the mature animal, from a pool of endoderm derived, self-renewing stem cells. Entero-endocrine cells share many structural/functional and developmental properties with sensory neurons, which hints at the possibility of an ancient evolutionary relationship between these two cell types. We will survey in this article recent findings that emphasize the similarities between entero-endocrine cells and sensory neurons in vertebrates and insects, for which a substantial volume of data pertaining to the entero-endocrine system has been compiled. We will then report new findings that shed light on the specification and morphogenesis of entero-endocrine cells in Drosophila. In this system, presumptive intestinal stem cells (pISCs), generated during early metamorphosis, undergo several rounds of mitosis that produce the endocrine cells and stem cells (ISCs) with which the fly is born. Clonal analysis demonstrated that individual pISCs can give rise to endocrine cells expressing different types of peptides. Immature endocrine cells start out as unpolarized cells located basally of the gut epithelium; they each extend an apical process into the epithelium which establishes a junctional complex and apical membrane specializations contacting the lumen of the gut. Finally, we show that the Drosophila homolog of ngn3, a bHLH gene that defines the entero-endocrine lineage in mammals, is expressed and required for the differentiation of this cell type in the fly gut.

PURPOSE: This study aimed to demonstrate the value of the chief compliant and patient history to accurately diagnose patient pathology without requiring ocular examination or imaging in an outpatient neuro-ophthalmology clinic. METHODS: We prospectively evaluated 115 consecutive patients at our institution from January to April 2009. The attending neuro-ophthalmologist committed to a single most likely diagnosis while solely being exposed to patient demographic information (age, gender, race) and chief complaint, but was otherwise blinded to ocular examination or imaging. The validity of the initial diagnosis was assessed by further acquiring subjective and objective findings and the percentage of correct diagnoses was determined. RESULTS: Patient cases were categorized based on the neuro-ophthalmologic localization of the final diagnoses: afferent nervous system, central nervous system (CNS), efferent nervous system, orbital system, and pupillary system. Correct diagnoses by chief complaint and patient history were 84%, 100%, 86%, 80%, 50% and 100% for afferent, central, efferent, orbit, pupil, and other neuro-ophthalmic diseases, respectively. Over half the cases were correctly diagnosed by chief complaint alone, which improved to 88% when combined with the patient history. CONCLUSIONS: A simple combination of patient history and chief complaint predicts an overall diagnostic accuracy in approximately 90% of cases. Our study demonstrates the remarkable diagnostic value of patient history in neuro-ophthalmologic clinic practice.

Introduction

Intravesical bacillus Calmette-Guérin (BCG) therapy is the gold standard adjuvant treatment for patients with high-grade non-muscle-invasive bladder cancer (NMIBC). Despite the association between metabolic syndrome (MetS) and bladder cancer, the association between MetS and BCG failure is unknown. The objective of this study was to characterize disease recurrence following BCG in patients with and without MetS.

Methods

We retrospectively evaluated the records of patients undergoing TURBT at our institution in 2012-2015 for NMIBC and identified those who received adjuvant BCG therapy. MetS was defined as having three of four components: diabetes mellitus, hyperlipidemia, hypertension, or body mass index (BMI)≥30kg/m². The primary outcome was recurrence or progression. Descriptive statistics, chi-squared analysis, Kaplan-Meier survival analysis, and Cox multivariable regression analyses were performed.

Results

High grade was present in 83/90 (92.2%) patients. MetS was present in 27/90 (30%) patients. Median follow-up was 20 months. On Kaplan-Meier analysis, patients with MetS had worse DFS compared with patient without MetS. On multivariable analysis, BMI≥30 kg/m² was a significant predictor of recurrence or progression (HR 2.94, 95% CI: 1.43-6.03). Presence of MetS did not significantly affect the type of BCG failure.

Conclusions

The association between MetS and failure to respond to BCG therapy is multifactorial but is in part associated with obesity. Elevated BMI is strongly associated with recurrence or progression. Further studies are warranted to investigate the relationship between increased adiposity and response to BCG, especially as other novel immunotherapeutic agents are likely to enter the NMIBC space.

Background

Intravesical Mitomycin-C (MMC) following transurethral resection of bladder tumor (TURBT), while efficacious, is associated with side effects and poor utilization. Continuous saline bladder irrigation (CSBI) has been examined as an alternative. In this study we sought to compare the rates of recurrence and/or progression in patients with NMIBC who were treated with either MMC or CSBI after TURBT.

Methods

We retrospectively reviewed records of patients with NMIBC at our institution in 2012-2015. Perioperative use of MMC (40 mg in 20 mL), CSBI (two hours), or neither were recorded. Primary outcome was time to recurrence or progression. Descriptive statistics, chi-squared analysis, Kaplan-Meier survival analysis, and Cox multivariable regression analyses were performed.

Results

205 patients met inclusion criteria. Forty-five (22.0%) patients received CSBI, 71 (34.6%) received MMC, and 89 (43.4%) received no perioperative therapy. On survival analysis, MMC was associated with improved DFS compared with CSBI (p = 0.001) and no treatment (p = 0.0009). On multivariable analysis, high risk disease was associated with increased risk of recurrence or progression (HR 2.77, 95% CI: 1.28-6.01), whereas adjuvant therapy (HR 0.35, 95% CI: 0.20-0.59) and MMC (HR 0.43, 95% CI: 0.25-0.75) were associated with decreased risk.

Conclusions

Postoperative MMC was associated with improved DFS compared with CSBI and no treatment. The DFS benefit seen with CSBI in other studies may be limited to patients receiving prolonged irrigation. New intravesical agents being evaluated may consider saline as a control given our data demonstrating that short-term CSBI is not superior to TURBT alone.