Quantification of interstitial cells of Cajal and fibrosis during gastric per-oral endoscopic myotomy and its association with clinical outcomes.

Background and study aims Alterations to interstitial cells of Cajal (ICC) and collagen fibrosis have been implicated in the pathogenesis of gastroparesis. We aimed to evaluate the feasibility and safety of pyloric muscle sampling during gastric peroral endoscopic myotomy (G-POEM) and the association between pyloric ICC density and degree of fibrosis with clinical outcomes. Patients and methods This was a single-center prospective study of gastroparetic patients who underwent G-POEM and intraprocedural pyloric muscle biopsies between January 2022 and April 2023. ICC count was estimated using CD117 stain and trichome for collagen fibrosis. Clinical response to G-POEM was defined as an improvement of ≥ 1 point on the Gastroparesis Cardinal Symptom Index. Results Fifty-six patients (median age 60 years, 71.4% women) underwent G-POEM (100% technical success; 71.4% clinical response). ICC depletion (< 10/high-power field) and fibrosis were encountered in 70.4% and 75% of the cases, respectively. There was no difference in mean ICC count between G-POEM responders vs. non-responders (7±3.6 vs. 7.7±3.3; P = 0.9). There was no association between ICC density or degree of fibrosis with the etiology of gastroparesis, duration of symptoms, gastric emptying rate, or pyloric impedance planimetry. Patients who did not respond to G-POEM had a significantly higher degree of moderate/severe fibrosis when compared with those who responded (81.3% vs. 25%; P = 0.0002). Conclusions Pyloric muscle biopsies during G-POEM was feasible and safe. ICC depletion and pyloric muscle fibrosis are common in gastroparetic patients. The degree of fibrosis may be related to pyloric dysfunction and clinical response to G-POEM. Additional studies are needed to confirm these results.

Low delayed bleeding and high complete closure rate of mucosal defects with the novel through-the-scope dual-action tissue clip after endoscopic resection of large nonpedunculated colorectal lesions (with video).

BACKGROUND AND AIMS: Complete closure after endoscopic resection of large nonpedunculated colorectal lesions (LNPCLs) can reduce delayed bleeding but is challenging with conventional through-the-scope (TTS) clips alone. The novel dual-action tissue (DAT) clip has clip arms that open and close independently of each other, facilitating tissue approximation. We aimed to evaluate the rate of complete closure and delayed bleeding with the DAT clip after endoscopic resection of LNPCLs. METHODS: This was a multicenter prospective cohort study of all patients who underwent defect closure with the DAT clip after EMR or endoscopic submucosal dissection (ESD) of LNPCLs ≥20 mm from July 2022 to May 2023. Delayed bleeding was defined as a bleeding event requiring hospitalization, blood transfusion, or any intervention within 30 days after the procedure. Complete closure was defined as apposition of mucosal defect margins without visible submucosal areas <3 mm along the closure line. RESULTS: One hundred seven patients (median age, 64 years; 42.5% women) underwent EMR (n = 63) or ESD (n = 44) of LNPCLs (median size, 40 mm; 74.8% right-sided colon) followed by defect closure. Complete closure was achieved in 96.3% (n = 103) with a mean of 1.4 ± .6 DAT clips and 2.9 ± 1.8 TTS clips. Delayed bleeding occurred in 1 patient (.9%) without requiring additional interventions. CONCLUSIONS: The use of the DAT clip in conjunction with TTS clips achieved high complete defect closure after endoscopic resection of large LNPCLs and was associated with a .9% delayed bleeding rate. Future comparative trials and formal cost-analyses are needed to validate these findings. (Clinical trial registration number: NCT05852457.).

Endoscopic blind limb reduction with septotomy: a novel endoscopic approach to candy cane syndrome after Roux-en-Y gastric bypass.

Video 1The endoscopic blind limb reduction with septotomy procedure.

Ultrasound Assisted Endoscopic Gastric Bypass (USA-EGB): a potential endoscopic alternative to surgical bypass, a pre-clinical proof of concept study.

Background and study aims Endoscopic weight loss procedures have gained traction as minimally invasive options for the primary treatment of obesity. Thus far, we have developed endoscopic procedures that reliably address gastric restriction but result in significantly less weight loss than surgical gastrointestinal bypass. The goal of this nonsurvival study was to assess the technical feasibility of an endoscopic procedure, that incorporates both gastric restriction and potentially reversible gastrointestinal bypass. Methods Ultrasound-assisted endoscopic gastric bypass (USA-EGB) was performed in three consecutive live swine, followed by euthanasia and necropsy. Procedure steps were: 1) balloon-assisted enteroscopy that determines the length of the bypassed limb; 2) endoscopic ultrasound-guided gastroenterostomy that creates a gastrointestinal anastomosis using a lumen apposing metal stent; 3) endoscopic pyloric exclusion that disrupts transpyloric continuity resulting in complete gastrointestinal bypass; and 4) gastric restriction that reduces gastric volume. Results Complete gastrointestinal bypass and gastric restriction was achieved in all three swine. The mean total procedure time was 131 minutes (range 113-143), mean length of the bypassed limb was 92.5 cm and 180 cm, using short and long overtubes, respectively. There were no significant complications. Conclusions We successfully described USA-EGB in three consecutive live swine. Further studies are needed to access the procedures safety, efficacy, and clinical use.

Can the rate and location of sessile serrated polyps be part of colorectal Cancer disparity in African Americans?

BACKGROUND: Up to 30% of colorectal cancers develop through the serrated pathway. African Americans (AAs) suffer a disproportionate burden of colorectal cancer. The aim of this study was to evaluate clinicopathological features of AA patients diagnosed with sessile serrated polyps (SSPs). METHODS: We conducted a retrospective study of all colonoscopies (n = 12,085) performed at Howard University Hospital, from January 1st, 2010 to December 31st, 2015, of which 83% were in AA patients, (n = 10,027). Among AAs, pathology reports confirmed 4070 patients with polyps including 252 with SSPs. Demographic and clinical variables (i.e. sex, age, BMI, anatomic location, clinical symptoms, polyp size, and clinical indications were collected at colonoscopy. RESULTS: In the AA population, the median age was 56 with interquartile range (IQR) of 51 to 62 years, 54% were female, and 48% had a BMI > 30. The most common reason for colonoscopy was screening (53%), whereas the prevalent reasons for diagnostic colonoscopies were changes in bowel habits (18%) and gastrointestinal bleeding (17%). The total number of SSPs among the 252 AA (diagnosed with SSPs) was 338. Of these, 9% (n = 29/338) had some degree of cytological dysplasia, primarily in the ascending colon (n = 6/42, 14%), Transverse colon (n = 2/16, 13%) and rectosigmoid (n = 19/233, 8%). About 24% of patients had more than 2 polyps. Most patients (76%) had distal SSPs (rectal and rectosigmoid), in comparison to 14% of proximal polyps and 10% of bilateral locations. Median SSA/P size for all locations was 0.6 cm. CONCLUSION: The prevalence of SSPs accounts for 6% of all polyps in AA patients and was diagnosed in 2.5% of all colonoscopies (n = 252/10,027), which is higher than Caucasians in the US. SSPs were predominantly located in the left side, as compared to published literature showing the predominance in the right side of the colon. Screening of CRC will have the chance to detect high risk SSA/P in this population.

Mice Lacking M1 and M3 Muscarinic Acetylcholine Receptors Have Impaired Odor Discrimination and Learning.

The cholinergic system has extensive projections to the olfactory bulb (OB) where it produces a state-dependent regulation of sensory gating. Previous work has shown a prominent role of muscarinic acetylcholine (ACh) receptors (mAChRs) in regulating the excitability of OB neurons, in particular the M1 receptor. Here, we examined the contribution of M1 and M3 mAChR subtypes to olfactory processing using mice with a genetic deletion of these receptors, the M1-/- and the M1/M3-/- knockout (KO) mice. Genetic ablation of the M1 and M3 mAChRs resulted in a significant deficit in odor discrimination of closely related molecules, including stereoisomers. However, the discrimination of dissimilar molecules, social odors (e.g., urine) and novel object recognition was not affected. In addition the KO mice showed impaired learning in an associative odor-learning task, learning to discriminate odors at a slower rate, indicating that both short and long-term memory is disrupted by mAChR dysfunction. Interestingly, the KO mice exhibited decreased olfactory neurogenesis at younger ages, a deficit that was not maintained in older animals. In older animals, the olfactory deficit could be restored by increasing the number of new born neurons integrated into the OB after exposing them to an olfactory enriched environment, suggesting that muscarinic modulation and adult neurogenesis could be two different mechanism used by the olfactory system to improve olfactory processing.

An Unusual Case of Invasive Kaposi's Sarcoma with Primary Effusion Lymphoma in an HIV Positive Patient: Case Report and Literature Review.

We report a case of AIDS-related Kaposi's sarcoma (KS) with Primary Effusion Lymphoma (PEL) in a 28-year-old, African American male. Kaposi's sarcoma is an AIDS defining disease and typically will disseminate early in the course of the disease affecting the skin, mucous membranes, gastrointestinal tract, lymph nodes, and lungs. This case reports an unusual presentation of the disease along with primary effusion lymphoma. Although the most common organ systems affected by KS are the respiratory and the gastrointestinal systems, the lungs of this patient did not show any evidence of KS. Additionally, the patient demonstrates the rarely seen liver and unique pancreatic involvement by KS along with unusual synchronous bilateral pleural and peritoneal cavity involvement by PEL, adding to the distinct pattern of invasive AIDS-related Kaposi's sarcoma.

Complication of Invasive Molar Pregnancy with Clostridium perfringens Sepsis.

Clostridium perfringens (CP) is an anaerobic, Gram-positive bacillus associated with malignant diseases and near-term pregnancies. The necrotic tissue that results from these disease processes fuels the proliferation of CP, leading to gas gangrene and subsequently sepsis. Herein, we report a case of a 41-year-old female patient with a history of invasive molar pregnancy that was further complicated with a CP infection. Although past research has shown a link between Clostridium infection and choriocarcinoma (Chern-Horng and Hsieh, 1999), no previous cases of CP infection have been associated with invasive molar pregnancy. We also report complete resolution of the CP sepsis and its associated symptoms following the hysterectomy.

The stoichiometric production of IL-2 and IFN-γ mRNA defines memory T cells that can self-renew after adoptive transfer in humans.

Adoptive immunotherapy using ex vivo-expanded tumor-reactive lymphocytes can mediate durable cancer regression in selected melanoma patients. Analyses of these trials have associated the in vivo engraftment ability of the transferred cells with their antitumor efficacy. Thus, there is intensive clinical interest in the prospective isolation of tumor-specific T cells that can reliably persist after transfer. Animal studies have suggested that central memory CD8(+) T cells (T(CM)) have divergent capabilities including effector differentiation to target antigen and stem cell-like self-renewal that enable long-term survival after adoptive transfer. We sought to isolate human melanoma-specific T(CM) to define their in vivo fate and function after autologous therapeutic transfer to metastatic patients. To facilitate the high-throughput identification of these rare cells from patients, we report that T(CM) have a defined stoichiometric production of interleukin-2 (IL-2) and interferon-γ (IFN-γ) mRNA after antigen stimulation. Melanoma-specific T cells screened for high relative IL-2 production had a T(CM) phenotype and superior in vitro proliferative capacity compared to cells with low IL-2 production. To investigate in vivo effector function and self-renewal capability, we allowed melanoma-specific T(CM) to undergo in vitro expansion and differentiation into lytic effector clones and then adoptively transferred them back into their hosts. These clones targeted skin melanocytes in all five patients and persisted long term and reacquired parental T(CM) attributes in four patients after transfer. These findings demonstrate the favorable engraftment fitness for human T(CM)-derived clones, but further efforts to improve their antitumor efficacy are still necessary.