Gastroparesis and Gastroparesis Syndromes as Neuromuscular Disorders.

Gastroparesis syndromes (GpS) are a spectrum of disorders presenting with characteristic symptoms increasingly recognized as being gastrointestinal (GI) neuromuscular disorders (NMDs). This review focuses on GpS as a manifestation of neurologic disorders of GI NMD. GpS can be associated with systemic abnormalities, including inflammatory, metabolic, and serologic disorders, as well as autoimmune antibodies via nerve and muscle targets in the GI tract, which can be treated with immunotherapy, such as intravenous immunoglobulin. GpS are associated with autonomic (ANS) and enteric (ENS) dysfunction. Disorders of ANS may interact with the ENS and are the subject of continued investigation. ENS disorders have been recognized for a century but have only recently begun to be fully quantified. Anatomic structural changes in the GI tract are increasingly recognized in GpS. Detailed descriptions of anatomic changes in GpS, and their correlation with physiologic findings, have opened a new era of investigation. The management of GpS, when viewed as GI NMD, has shifted the paradigms of both diagnosis and treatment. This article concludes with current approaches to GpS directed at underlying neuromuscular pathology.

Safety and efficacy of over-the-scope clips versus standard therapy for high-risk nonvariceal upper GI bleeding: systematic review and meta-analysis.

BACKGROUND AND AIMS: Upper GI bleeding (UGIB) is a common condition associated with significant morbidity and mortality. Endoscopic hemostasis remains the mainstay of therapy and is mainly aimed at effective hemostasis and prevention of rebleeding. Lesions with high-risk stigmata can have rebleeding rates of as high as 26.3%. Rebleeding is associated with increased mortality and reduced success rates of endoscopic retreatment. The over-the-scope-clip (OTSC) is a device with widespread endoscopic indications including hemostasis for nonvariceal UGIB (NVUGIB). The current study presents a systematic review and meta-analysis comparing OTSCs versus standard therapy (STD) for NVUGIB. METHODS: Multiple databases were searched through April 2022 for studies comparing OTSCs and STD for NVUGIBs. Primary outcomes were clinical success rates, rebleeding rates, and procedure times, and secondary outcomes were mortality rates and length of hospitalization. Meta-analysis was performed to determine pooled odds ratios to compare outcomes between the OTSC and STD groups. RESULTS: Ten studies, including 4 randomized controlled trials, with 914 patients were included in the final analysis. Of patients with NVUGIB, 431 were treated with OTSCs and 483 with STD. Patients treated with OTSCs had an overall lower risk of 7-day (risk ratio [RR], .41; 95% confidence interval [CI], .24-.68; I2 = 0%) and 30-day rebleeding (RR, .46; 95% CI, .31-.65; I2 = 0%). Clinical success rates were higher with OTSCs compared with STD (RR, 1.36; 95% CI, 1.06-1.75). Mean procedure time was shorter in the OTSC group by 6.62 minutes (95% CI, 2.58-10.67) versus the STD group (I2 = 84%). There was no statistically significant difference in terms of mortality between the OTSC and STD groups (RR, .55; 95% CI, .24-1.24; I2 = 0%). Length of hospitalization was comparable between both groups, with a pooled mean difference for OTSCs versus STD of .87 days (95% CI, -1.62 to 3.36 days; I2 = 71%). CONCLUSIONS: Although our study was limited to high-risk NVUGIB, our analysis showed that hemostasis with OTSCs is associated with a lower 7-day and 30-day rebleeding rates, higher clinical success rates, and shorter procedure time with similar mortality rates and length of hospital stay as compared with STD.

Gastroparesis syndromes: emerging drug targets and potential therapeutic opportunities.

INTRODUCTION: Gastroparesis (Gp) and related disorders such as chronic unexplained nausea and vomiting and functional dyspepsia, known as gastropareis syndromes (GpS), have large unmet needs. Mainstays of GpS treatments are diet and drugs. AREAS COVERED: The purpose of this review is to explore potential new medications and other therapies for gastroparesis. Before discussing possible new drugs, the currently used drugs are discussed. These include dopamine receptor antagonists, 5-hydroxytryptamine receptor agonists and antagonists, neurokinin-1 receptor antagonists and other anti-emetics. The article also considers future drugs that may be used for Gp, based on currently known pathophysiology. EXPERT OPINION: Gaps in knowledge about the pathophysiology of gastroparesis and related syndromes are critical to developing therapeutic agents that will be successful. Recent major developments in the gastroparesis arena are related to microscopic anatomy, cellular function, and pathophysiology. The major challenges moving forward will be to develop the genetic and biochemical correlates of these major developments in gastroparesis research.

A Rare Case of Serrated Polyposis Syndrome with the MSH6 and SMARCA4 variants.

Serrated polyposis syndrome (SPS) is the most common form of polyposis syndrome and has been shown to increase the risk of colorectal cancer (CRC). The genetic pathway of CRC in SPS is different from the classic adenomatous polyposis coli (APC) pathway, which accounts for 70-80% of cases of CRC. Most commonly, SPS mutations include BRAF and KRAS, with activation of the RAS-RAF-MAP kinase pathway involved in the pathogenesis of serrated lesions. We present a rare case of SPS in a 32-year-old woman with MSH6 and SMARCA4 variants, which have not previously been reported in the literature. LEARNING POINTS: Patients with serrated polyposis syndrome should receive frequent colon cancer screening.Patients and their relatives should undergo surveillance.