Citations

ABSTRACT Background Chronic megacolon is an uncommon neurogastrointestinal disorder typically characterized by a persistent increase in colonic diameter. Methods Our aim was to identify adults with medical treatment‐refractory constipation without radiographic criteria for megacolon but with increased colonic compliance (refractory constipation with colonic hypercompliance (RCCH)), and to compare the colonic compliance in 7 identified patients with “RCCH” to colonic compliance in 10 patients with chronic megacolon by radiographic criteria (i.e., megacolon) and 40 healthy volunteers. After endoscopic placement, compliance of left or transverse colon was measured using a 10‐cm‐long infinitely compliant balloon connected to an electronically controlled rigid piston barostat. The barostat inflated the balloon from 0 to 44 mmHg in 4‐mmHg steps at 30‐s intervals to measure colonic compliance (pressure‐volume relationship). Eligibility criteria for inclusion were increased colonic compliance based on a functional assessment without meeting radiographic criteria for megacolon (i.e., RCCH). In the three groups, we compared colonic volumes at intra‐balloon pressure of 8, 16, 20, 32, and 44 mmHg, the pressure at half maximum volume, and the slope of the colonic compliance curve using ANOVA on ranks and Dunn's pairwise comparison test. Other features of colonic motility were documented. Results Colonic volumes at all pressures (8‐44 mmHg) and the pressure at half maximum volume were significantly greater in patients with megacolon and RCCH than in healthy controls ( p < 0.001 for both), but compliance was not significantly different between RCCH and megacolon. Conclusion A subset of patients with medically‐refractory chronic constipation has colonic compliance similar to that of patients with megacolon.

Locally advanced basal cell carcinoma (BCC) is an uncommon and complex presentation of BCC. These tumors can present as extensive nonhealing ulcers and require skin biopsy to rule out other causes, including malignant, infectious, and inflammatory etiologies. In this case report, a 57-year-old female without significant past medical history presented with a 5-year history of a chronic progressive ulcer involving the neck and back. Histopathological study of the tissue identified nodular and infiltrative BCC, prompting further multidisciplinary treatment and management with vismodegib, radiation, and surgery.

ABSTRACT Background Gastric emptying (GE) scintigraphy with 4‐h imaging and a radiolabeled chicken egg‐based meal (320 kcal, 30% fat) is the standard test for gastroparesis at Mayo Clinic, with an intraindividual coefficient of variation (COV intra ) of 23.8% for GE half emptying time (T 1/2 ). Alternative meals for patients with dietary restrictions, including egg allergies or vegan diets, are lacking, limiting test accessibility. The study aimed to establish a vegan, lactose‐, nut‐, and gluten‐free meal with similar caloric and fat content to the egg meal and to assess its performance in GE studies. Methods In Vitro: 99m Tc binding to egg meal over 4 h was compared to a calorically and nutritionally similar vegan alternative, JUST Egg, using a validated in vitro model simulating gastric conditions of pH, pepsin, and stirring. In Vivo: 10 healthy participants underwent randomized crossover GE scintigraphy with standard and vegan meals, spaced ≥ 3 days apart to measure GE% at 2 h, 4 h, and GE T 1/2 . Group comparisons and variance analysis included Rank Sum tests and Bland–Altman plots. Key Results In Vitro: A strong correlation ( R = 0.975, p ‐value < 0.01) between 99m Tc binding in the egg and vegan egg models was observed. Minimal variance (< 10%) was recorded at all time points. In Vivo: GE at 4 h and GE T 1/2 showed non‐statistically significant mean differences, < 2% and < 10 min respectively, between both meals. The intra‐individual variability was 18.8%. Conclusions and Inferences The vegan meal demonstrated in vitro stability, in vivo performance comparable to the egg meal, and a COV intra of 18.8%, which was lower than the 23.8% reported in repeat egg meal GE studies. Trial Registration ClinicalTrials.gov number NCT06991036 ( https://clinicaltrials.gov/study/NCT06991036?term=NCT06991036&rank=1 )

Abstract: Melanoma exhibits a broad spectrum of histopathologic variations, including rare forms with neural differentiation. Neurotropism in melanoma encompasses both perineural invasion and neural-like transformation, but the prognostic implications of these features remain uncertain. Although (peri)neural invasion is well documented, true neural differentiation in melanomas is exceedingly rare. In this study, we describe an unusual case of primary cutaneous malignant melanoma exhibiting extensive Wagner–Meissner-like bodies, a feature more commonly associated with benign neural tumors and nevi. In this case, histopathology revealed a dual-component lesion with a neurotized and an epithelioid melanocytic component, both showing PRAME expression and p16 loss. Chromosomal microarray identified heterozygous loss of 9p22.1p13.1 (including CDKN2A / CDKN2B ), and loss of 10q22.2q26.3 (including PTEN ), supporting malignancy. These findings suggest that in this case, Wagner–Meissner-like bodies likely represent neurotization rather than a benign or collision lesion, highlighting the need for integrated histopathologic, immunohistochemical, and molecular analysis in challenging melanocytic neoplasms.

This pilot, randomized, double-blind trial in a relatively small sample of patients with IBS-related pain shows rimegepant significantly reduced sensations of gas, urgency, and pain during rectal distention and decreased rectal compliance. Decrease in compliance implies that changes in physical properties or distensibility of rectum did not contribute to alterations in rectal sensation. Same dose of rimegepant did not significantly impact daily abdominal pain, BM frequency, or colonic transit. There were no serious adverse events.

INTRODUCTION: To perform a proof-of-concept study to evaluate the performance of individual and combined anorectal manometry and balloon expulsion testing (BET) parameters for diagnosing dyssynergic defecation (DD) using machine learning (ML). METHODS: A single gastrointestinal motility specialist assessed (2008–2018) 307 patients. A ML model was constructed on anorectal manometry/BET data. BET was weight-based in 235 patients and time-based in 72 patients. Missing data were imputed. Data were split 75% train/25% test with preprocessing performed. Five common ML models were trained, and performance was compared using receiver operating characteristic (ROC) area under the curve and accuracy based on 100 bootstrapped samples. The most accurate models were fine-tuned and evaluated on the test set. RESULTS: The median age was 40 years, body mass index 22.2 kg/m 2 , and 81% were women. Two-hundred and 22 (72.3%) patients had a clinical diagnosis of DD. Compared with patients without clinical diagnosis of DD, patients with DD had significantly lower rectoanal pressure gradient (RAG) (median −34.7 [IQR −57.1, −13.0] vs −24.6 [IQR −44.5, −2.4] mm Hg, P = 0.009) and more abnormal BET (59.5% vs 11.8%, P < 0.001). Four features were retained in the optimized model as predictors of DD: abnormal BET, greater resting anal pressure (RAP), and more negative RAG. The optimal parameter was abnormal BET ( P = 0.003), but combinations of 2 manometry results (RAP and RAG) yielded positive predictive values (PPVs) >80%. The optimized logistic regression model had an area under the curve of 0.878, with a sensitivity of 75.0% and specificity of 81.8% at a probability threshold of 0.704. DISCUSSION: Abnormal BET, or a combination of 2 manometric parameters (RAP and RAG), provides >80% positive predictive value for diagnosing DD in patients with chronic constipation.

ABSTRACT Background In the United States, metoclopramide is the only medication approved for gastroparesis. There is a need to reappraise the main considerations involved in the approval of pharmacological treatments of gastroparesis. Objectives and Methods We conducted a literature review to address issues that might impact the approval of medications for gastroparesis. We appraised the epidemiology, clinical presentations, variations in diagnostic tests, and their thresholds for identification of gastroparesis. Based on the review, we proposed trial designs for proof of efficacy and safety of novel medications for gastroparesis. Results Based on epidemiological studies, the age‐adjusted prevalence in US population is 152,005 for all categories (definite, probable and possible) of gastroparesis. The major symptoms of gastroparesis are nausea, vomiting, early satiety and postprandial fullness and may lead to hospitalisation or emergency department visits. It is essential to appraise gastric emptying with a solid meal over at least 3 h using scintigraphy or a stable isotope breath test. Diagnostic thresholds have been established for these diagnostic tests and at present, reproducibility, normative data, and coefficient of variation are well established for the 320‐kcal real egg solid meal. Based on published guidelines on clinical efficacy of medications used in gastroparesis, we propose targeting the gastroparesis symptom subscales, such as nausea and vomiting, with pharmacological agents specifically directed at their causative mechanisms rather than targeting the underlying dysmotility. Conclusion The evidence documented here justifies consideration of gastroparesis as an orphan disease, as well as an innovative approach to supplement the regulatory bodies' recommendations and guidance to industry. We propose treatment trials of 4‐weeks duration and considering the use of specific symptoms of gastroparesis as clinical endpoints based on a pharmaceutical agent's mechanism of action, rather than using a total gastroparesis symptom score. Such an approach would include evidence of safety and efficacy of new medications targeting gastroparesis subscales, and approval for marketing would be based on the symptoms specifically ameliorated in robust trials.

Patzelt et al. previously characterized dermal-binding autoantibodies using an indirect immunofluorescence (IIF) mosaic assay with cells transfected with p200-laminin β4, laminin-332 or collagen VII subunits among specimens showing a dermal pattern on IIF using salt-split skin (IIF-SSS) and IgG. This study expanded testing to include specimens with either a dermal or mixed pattern on IIF-SSS and demonstrated improved test sensitivity with modified testing methods.