Clinical and Experimental Gastroenterology最新文献

Ulcerative colitis (UC) is a chronic and progressive inflammatory disorder that affects the colon. The advent of advanced therapies such as biologic agents and small molecules has revolutionized the management of UC. Despite the expanding therapeutic armamentarium of advanced therapies to treat UC, the overall net remission rates and durability of currently available agents are relatively low. This highlights the need for further drug development and more innovative clinical trial design. There are currently multiple emerging agents in the pipeline for the management of UC. This includes agents with alternative routes of administration such as oral or subcutaneous tumor necrosis factor inhibitors or novel mechanisms of action such as toll-like receptor 9 (TLR9) agonist cobitolimod and phosphodiesterase 4 inhibitor apremilast. In this review, we will highlight novel and emerging advanced therapies currently in the pipeline for the management of UC.

In patients with gastrointestinal stromal tumors (GIST), systemic treatment after disease progression on imatinib is challenging. Sunitinib and regorafenib are approved in the second- and third-line setting, respectively, with activity against certain secondary mutations with comparatively much lower response rates and survival increment compared to imatinib. All three of these drugs were serendipitously found to have activity in GIST, starting with imatinib, which was formulated for its ability to inhibit BCR-ABL in chronic myelogenous leukemia. Ripretinib is a drug that was specifically developed as a more potent KIT tyrosine kinase inhibitor (TKI), with broad-spectrum activity against the mutations encountered in GIST. Encouraging responses in early and later lines of treatment in the Phase 1 trial of ripretinib in GIST led to the rapid development of this novel drug. In a Phase 3 randomized clinical trial with cross-over, ripretinib demonstrated superior PFS and overall survival (OS) in 4th-line treatment and beyond compared to placebo. This established 150 mg once daily ripretinib as the standard of care in this setting. Ripretinib is generally well tolerated, with common adverse effects of hair loss, diarrhea, cramps, fatigue and nausea. The favorable safety profile and efficacy of ripretinib prompted its evaluation in a randomized phase 3 trial in the 2nd-line treatment setting. However, it did not result in a longer PFS duration than sunitinib. Although the efficacy of ripretinib in this unselected patient population was not significantly different from that of sunitinib, the tolerability profile was better. This review article aims to review the efficacy and tolerability profile of ripretinib, together with its role in the setting of unresectable or metastatic GIST.

Gastric cancer with Virchow's lymph node metastasis (LNM) is not indicated for initial curative surgery. Although there have been some case reports of curative resections after pre-operative treatment, including immune checkpoint inhibitors (ICIs), there is no consensus regarding the optimal timing of surgery. We describe a rare case of initially unresectable gastric cancer treated preoperatively with nivolumab combined chemotherapy, which achieved a pathologically complete response. An 82-year-old man was referred for gastric cancer treatment. Contrast-enhanced computed tomography revealed stomach wall thickening and swollen left supraclavicular LN. This gastric cancer was assessed as unresectable due to the presence of Virchow's LNM; therefore, chemotherapy and ICI using S-1 plus oxaliplatin plus nivolumab were administered. After three courses of treatment, the primary tumor and Virchow's LN showed a marked reduction in size. The patient underwent Virchow's LNM resection as a preliminary step to determine indications for curative surgery. A pathological examination revealed no viable cancer cells were found inside the resected LN. The patient underwent distal gastrectomy. Pathological examination revealed complete degeneration of the primary tumor and regional LN without residual carcinoma. The patient did not receive adjuvant chemotherapy and survived with no evidence of recurrence for one year after the initial treatment.

Introduction: Hirschsprung's disease (HSCR) is a developmental defect of the enteric nervous system (ENS), which is caused by abnormal development of enteric neural crest cells. Its occurrence is caused by genetic factors and environmental factors. It has been reported that single nucleotide polymorphisms (SNPs) of proprotein convertase subtilisin/kexin type 2 (PCSK2) gene are associated with HSCR. However, the correlation of HSCR in southern Chinese population is still unclear.

Methods: We assessed the association of rs16998727 with HSCR susceptibility in southern Chinese children using TaqMan SNP genotyping analysis of 2943 samples, including 1470 HSCR patients and 1473 controls. The association test between rs16998727 and phenotypes was performed using multivariable logistic regression analysis.

Results: We got an unexpected result, PCSK2 SNP rs16998727 was not significantly different from HSCR and its HSCR subtypes: S-HSCR (OR = 1.08, 95% IC: 0.93~1.27, P_adj = 0.3208), L-HSCR (OR = 1.07, 95% IC: 0.84~1.36, P_adj = 0.5958) and TCA (OR = 0.94, 95% IC: 0.61~1.47, P_adj = 0.8001).

Conclusion: In summary, we report that rs16998727 (PCSK2 and OTOR) is not associated with the risk of HSCR in southern Chinese population.

Purpose: Esophageal mucosal admittance (MA) is a promising diagnostic method for gastroesophageal reflux disease (GERD). We conducted a study to describe the esophageal MA in patients with reflux symptoms and determine its diagnostic accuracy.

Patients and methods: We recruited 92 patients with ambulatory pH-impedance monitoring, upper gastrointestinal endoscopy, and MA measured by the tissue conductance meter. MA was measured during endoscopy at 5cm (distal esophagus) and 15cm above the Z line (middle esophagus), repeated at least five times at each position, and median MA was obtained. Afterwards, two biopsies were taken 5cm above the Z line for histopathological evaluation using the Esohisto criteria. Patients were classified as GERD or non-GERD according to the 2018 Lyon consensus.

Results: The mean age was 43.2 years, and 42 patients were males. The most common symptoms were regurgitation (75.0%), belching (65.2%), and heartburn (46.7%). Twenty-three (32.3%) were diagnosed with GERD using the Lyon consensus, and 24 (26.1%) had esophagitis on histopathology. The median MA at the distal and middle esophagus was moderately correlated. The median MA at both positions was higher in the GERD group but only statistically significant in the middle esophagus. MA was not associated with pH-impedance parameters and esophagitis on histopathology. The diagnostic model developed using the logistic regression did not have good accuracy.

Conclusion: MA was not different between GERD and non-GERD patients.

Patients with gastrointestinal (GI) bleeding present to the emergency department (ED) with a wide spectrum of illness severity. Among the most critically ill patients, comorbidities and other risk factors, such as liver disease and anticoagulation, can complicate their management. These patients are resource-intensive to stabilize and resuscitate, often requiring the continuous attention of multiple ED staff members along with rapid mobilization of specialty care. At a tertiary care hospital with the ability to provide definitive care for the most critically ill patients with GI bleeding, we introduced a multi-disciplinary team activation pathway to bring together specialists to immediately respond to the ED. We designed a Code GI Bleed pathway to expedite hemodynamic stabilization, diagnostics, source control, and timely disposition out of the ED to the intensive care unit or relevant procedural area of the hospital.

Introduction: Ectopic fat deposition is well appreciated as a key contributor to digestive and liver diseases. Bile acids have emerged as pleiotropic signalling molecules involved in numerous metabolic pathways. The aim was to study the associations of bile acids with ectopic fat deposition and lipid panel.

Methods: A single 3.0 Tesla magnetic resonance imaging scanner was employed to measure fat deposition in the pancreas, liver, and skeletal muscle in 76 adults. Blood samples were drawn to determine total bile acids and lipid panel. Linear regression analyses were run, taking into account age, sex, body mass index, and other covariates.

Results: The studied ectopic fat depots were not significantly associated with levels of total bile acids in serum. Total bile acids were significantly associated high-density lipoprotein cholesterol - consistently in both the unadjusted (p = 0.018) and all adjusted models (p = 0.012 in the most adjusted model). Low-density lipoprotein cholesterol, total cholesterol, and triglycerides were not significantly associated with total bile acids in both the unadjusted and all adjusted models.

Conclusion: Fat deposition in the pancreas, liver, and skeletal muscle is not associated with circulating levels of total bile acids. High-density lipoprotein cholesterol is the only component of lipid panel that is associated with total bile acids.

Gastroparesis (GP), a historically vexing disorder characterized by symptoms of nausea, vomiting, abdominal pain, early satiety, and/or bloating, in the setting of an objective delay in gastric emptying, is often difficult to treat and carries a tremendous burden on the quality of patients' lives, as well as the healthcare system in general. Though the etiology of GP has been fairly well defined, much work has been done recently to better understand the pathophysiology of GP, as well as to identify novel effective and safe treatment options. As our understanding of GP has evolved, many myths and misconceptions still abound in this rapidly changing field. The goal of this review is to identify myths and misconceptions regarding the etiology, pathophysiology, diagnosis, and treatment of GP, in the context of the latest research findings which have shaped our current understanding of GP. Recognition and dispelling of such myths and misconceptions is critical to moving the field forward and ultimately advancing the clinical management of what will hopefully become a better understood and more manageable disorder in the future.

Purpose: In spring 2020, Coronavirus Disease 2019 (COVID-19) "stay-at-home" orders may have led to later, more acute disease presentations of emergent conditions such as gastrointestinal bleeding (GIB). In this retrospective cohort study, we compared incidence and severity of GIB during the strictest COVID shutdown to pre-COVID periods.

Patients and methods: We compared weekly counts of emergency department (ED) visits for GIB between March 27 and May 7, 2020 (COVID period) and pre-COVID periods in 2019 and 2020 in a US statewide network of hospitals. We compared the severity of GIB presentations using incident rate ratios (IRR) of "severe" GIB (requiring ≥4 units of blood, endoscopic therapy, interventional radiology or surgical procedure), intensive care (ICU) admission and shock. We also looked for effect modification of demographic covariates on associations between year and GIB outcomes.

Results: Fewer patients presented to ED for GIB during COVID than during the same dates in 2019 (534 versus 904; IRR 0.59, 95% CI 0.53-0.66). A greater proportion of COVID-period ED visits required inpatient admission (73.6% vs 67.8%, p = 0.02) and had severe GIB (19.3% vs 14.9%, p = 0.03). Proportion of patients requiring transfusion (p < 0.001), with shock (p < 0.01), or with critical hemoglobin (p = 0.003) or lactate (p = 0.02) were worse during COVID. Non-white patients experienced disproportionately worse outcomes during COVID than in 2019, with greater absolute counts of shock (65 vs 62, p = 0.01 for interaction) or ICU admission (40 vs 35, p = 0.01 for interaction).

Conclusion: Fewer acute GIB presented during the pandemic period compared to the year prior. The severity of pandemic presentations was greater, driven by disproportionately worse outcomes in minorities.