Leveraging existing mid-end ultrasound machine for point-of-care intestinal ultrasound in low-resource settings: Prospective, real-world impact on clinical decision-making.

BACKGROUND: Point-of-care ultrasound (POCUS) has transformed inflammatory bowel disease (IBD) management, but the cost to purchase high-end equipment can be prohibitive. AIM: To assess prospectively the feasibility of POCUS using pre-existing mid-end ultrasound equipment without incurring additional cost. METHODS: Consecutive IBD patients underwent POCUS with or without faecal calprotectin (FCP) using a mid-end ultrasound machine. If POCUS with or without FCP could not guide management, we performed additional ileocolonoscopy or cross-sectional imaging. We evaluated the impact of POCUS on IBD management and its correlation with ileocolonoscopy or cross-sectional imaging. We analysed pregnant, paediatric and post-operative patients separately. RESULTS: Among 508 patients with IBD, we analysed 419 (60.4% Crohn's disease [CD]; 61.3% male, age [years]: 36 [18-78]) undergoing 556 POCUS sessions. POCUS with or without FCP independently influenced clinical management in 42.8% of patients with CD and 49.7% with ulcerative colitis (UC). POCUS helped avoid colonoscopy in 51.4% of patients with CD and 51.8% with UC, and cross-sectional imaging in 38.1% of suspected active small bowel CD. In patients with additional diagnostics, POCUS-based decisions remained unchanged in 81.2% with CD and 85% with UC. Sensitivity and specificity of POCUS compared to ileocolonoscopy were 80% and 94.4% for CD and 80.8% and 92.8% for UC, respectively. Sensitivity and specificity compared to cross-sectional imaging were 87.2% and 87.5%, respectively. CONCLUSION: POCUS using existing mid-end ultrasound equipment in low-resource settings influenced IBD clinical decision-making with excellent accuracy, often avoiding colonoscopy and cross-sectional imaging.

Evaluation of the Crosstalk Between the Host Mycobiome and Bacteriome in Patients with Chronic Pancreatitis.

The human microbiome is a diverse consortium of microbial kingdoms that play pivotal roles in host health and diseases. We previously reported a dysbiotic bacteriome in chronic pancreatitis patients with diabetes (CPD) compared with patients with it's nondiabetic (CPND) phenotype. In this study, we extended our exploration to elucidate the intricate interactions between the mycobiome, bacteriome, and hosts' plasma metabolome with the disease phenotypes. A total of 25 participants (CPD, n = 7; CPND, n = 10; healthy control, n = 8) were recruited for the study. We observed elevated species richness in both the bacterial and fungal profiles within the CP diabetic cohort compared to the nondiabetic CP phenotype and healthy control cohorts. Notably, the CP group displayed heterogeneous fungal diversity, with only 40% of the CP nondiabetic patients and 20% of the CP diabetic patients exhibiting common core gut fungal profiles. Specific microbial taxa alterations were identified, including a reduction in Bifidobacterium adolescentis and an increase in the prevalence of Aspergillus penicilloides and Klebsiella sp. in the disease groups. In silico analysis revealed the enrichment of pathways related to lipopolysaccharide (LPS), apoptosis, and peptidase, as well as reduced counts of the genes responsible for carbohydrate metabolism in the CP groups. Additionally, distinct plasma metabolome signatures were observed, with CPD group exhibiting higher concentrations of sugars and glycerolipids, while the CPND cohort displayed elevated levels of amino acids in their blood. The fatty acid-binding protein (FABP) concentration was notably greater in the CPD group than in the HC group (4.220 vs. 1.10 ng/ml, p = 0.04). Furthermore, compared with healthy controls, disease groups exhibited fewer correlations between key fungal taxa (Aspergillus sp., Candida sp.) and bacterial taxa (Prevotella copri, Bifidobacteria sp., Rumminococcaceae). Our study unveils, for the first time, a dysbiotic mycobiome and emphasizes unique host bacterial-mycobial interactions in CP patient with diabetes, potentially influencing disease severity. These findings provide crucial insights for future mechanistic studies aiming to unravel the determinants of disease severity in this complex clinical context. Supplementary Information: The online version contains supplementary material available at 10.1007/s12088-024-01207-8.

Recent Advancement and Future Perspective of Per Oral Endoscopic Myotomy.

Per oral endoscopic myotomy (POEM) has emerged as a preferred approach for the treatment of idiopathic achalasia and various esophageal motility disorders, offering a minimally invasive alternative to traditional laparoscopic Heller's myotomy. Over the past decade, POEM has solidified its status as the primary therapeutic choice in these conditions through constant improvements. Its evolution has been marked by continuous progress, driven by the integration of innovative technologies and sophisticated techniques. Notable advancements in the techniques include the advent of shorter myotomies and sling fiber-preserving gastric myotomies. The introduction of novel image-enhanced endoscopic techniques, such as red dichromatic imaging and much safer bipolar devices, promises to enhance safety and reduce the technical demands of the POEM procedure. Furthermore, significant strides have been made in understanding gastroesophageal reflux (GERD) following POEM, enabling the differentiation of "true reflux" from acidification resulting from fermentation through manual pH tracing assessment. This distinction aids in identifying cases necessitating treatment with proton pump inhibitors. Other treatment strategies of post-POEM GERD have expanded to the incorporation of NOTES fundoplication and device-assisted fundoplication if the necessity arises. This comprehensive review delves into recent developments in POEM, encompassing technical variations, the assessment and management of post-POEM reflux, outcomes in special populations, and future prospects. By exploring these facets, we aim to provide a comprehensive overview of the current state of POEM, shedding light on its evolution and the promising directions it is poised to take in the field of third-space endoscopy.

Endoscopic full thickness resection: techniques, applications, outcomes.

INTRODUCTION: Endoscopic full-thickness resection (EFTR) represents a pivotal advancement in the minimally invasive treatment of gastrointestinal lesions, offering a novel approach for the management of lesions previously deemed challenging or unreachable through conventional endoscopic techniques. AREAS COVERED: This review discusses the development, methodologies, applications, and clinical outcomes associated with EFTR, including exposed and device-assisted EFTR, the integration of endoscopic mucosal resection with EFTR in hybrid techniques, and the collaborative approach between laparoscopic and endoscopic surgery (LECS). It encapsulates a comprehensive analysis of the various EFTR techniques tailored to specific lesion characteristics and anatomical locations, underscoring the significance of technique selection based on the lesion's nature and situational context. EXPERT OPINION/COMMENTARY: The review underscores EFTR's transformative role in expanding therapeutic horizons for gastrointestinal tumors, emphasizing the importance of technique selection tailored to the unique attributes of each lesion. It highlights EFTR's capacity to facilitate organ-preserving interventions, thereby significantly enhancing patient outcomes and reducing procedural complications. EFTR is a cornerstone in the evolution of gastrointestinal surgery, marking a significant leap forward in the pursuit of precision, safety, and efficacy in tumor management.

Modulation of nuclear receptor 4A1 expression improves insulin secretion in a mouse model of chronic pancreatitis.

OBJECTIVES: Diabetes secondary to chronic pancreatitis (CP) presents clinical challenges due to insulin secretory defects and associated metabolic alterations. Owing to lack of molecular understanding, no pharmacotherapies to treat insulin secretory defects have been approved to date. We aimed to delineate the molecular mechanism of ß-cell dysfunction in CP. METHODS: Transcriptomic analysis was conducted to identify endocrine specific receptor expression in mice and human CP on microarray. The identified receptor (NR4A1) was overexpressed in MIN6 cells using PEI linear transfection. RNA-Seq analysis on NovaSeq 6000 of NR4A1 overexpressed (OE) MIN6 cells was performed to identify aberrant metabolic pathways. Upstream trigger for NR4A1OE was studied by InBio Discover and cytokine exposure. Downstream effect of NR4A1OE was examined by Fura2 AM based fluorometric and imaging studies of intracellular calcium. Mice with CP were treated with IFN-γ neutralizing monoclonal antibodies to assess NR4A1 expression and insulin secretion. RESULTS: Increased expression of NR4A1 associated with decreased insulin secretion in islets (humans: controls 9 ± 0.2, CP 3.7 ± 0.2, mice: controls 8.5 ± 0.2, CP 2.1 ± 0.1 µg/L). NR4A1OE in MIN6 cells (13.2 ± 0.1) showed reduction in insulin secretion (13 ± 5 to 0.2 ± 0.1 µg/mg protein/minute, p = 0.001) and downregulation of calcium and cAMP signaling pathways. IFN-γ was identified as upstream signal for NR4A1OE in MIN6. Mice treated with IFN-γ neutralizing antibodies showed decreased NR4A1 expression 3.4 ± 0.11-fold (p = 0.03), improved insulin secretion (4.4 ± 0.2-fold, p = 0.01), associated with increased Ca2+ levels (2.39 ± 0.06-fold, p = 0.009). CONCLUSIONS: Modulating NR4A1 expression can be a promising therapeutic strategy to improve insulin secretion in CP.

Plasma Metabolite Profiling Identifies Nondiabetic Chronic Pancreatitis Patients With Metabolic Alterations Progressing to Prediabetes Before HbA1c.

INTRODUCTION: Diabetes (T3cDM) secondary to chronic pancreatitis (CP) arises due to endocrine dysfunction and metabolic dysregulations. Currently, diagnostic tests are not available to identify patients who may progress from normoglycemia to hyperglycemia in CP. We conducted plasma metabolomic profiling to diagnose glycemic alterations early in the course of disease. METHODS: Liquid chromatography-tandem mass spectrometry was used to generate untargeted, targeted plasma metabolomic profiles in patients with CP, controls (n = 445) following TRIPOD guidelines. Patients were stratified based on glucose tolerance tests following ADA guidelines. Multivariate analysis was performed using partial least squares discriminant analysis to assess discriminatory ability of metabolites among stratified groups. COMBIROC and logistic regression were used to derive biomarker signatures. AI-ML tool (Rapidminer) was used to verify these preliminary results. RESULTS: Ceramide, lysophosphatidylethanolamine, phosphatidylcholine, lysophosphatidic acid (LPA), phosphatidylethanolamine, carnitine, and lysophosphatidylcholine discriminated T3cDM CP patients from healthy controls with AUC 93% (95% CI 0.81-0.98, P < 0.0001), and integration with pancreatic morphology improved AUC to 100% (95% CI 0.93-1.00, P < 0.0001). LPA, phosphatidylinositol, and ceramide discriminated nondiabetic CP with glycemic alterations (pre-diabetic CP); AUC 66% (95% CI 0.55-0.76, P = 0.1), and integration enhanced AUC to 74% (95% CI 0.55-0.88, P = 0.86). T3cDM was distinguished from prediabetic by LPA, phosphatidylinositol, and sphinganine (AUC 70%; 95% CI 0.54-0.83, P = 0.08), and integration improved AUC to 83% (95% CI 0.68-0.93, P = 0.05). CombiROC cutoff identified 75% and 78% prediabetes in validation 1 and 2 cohorts. Random forest algorithm assessed performance of integrated panel demonstrating AUC of 72% in predicting glycemic alterations. DISCUSSION: We report for the first time that a panel of metabolites integrated with pancreatic morphology detects glycemia progression before HbA1c in patients with CP.

Therapeutic endoscopy: Recent updates and future directions.

The landscape of therapeutic endoscopy has undergone a remarkable evolution over the past few decades, carving out a niche that merges innovative technology with advanced clinical practice. As we venture further into the 21st century, the horizon of this field continues to expand, driven by rapid advancements in technology and a deeper understanding of gastrointestinal pathology. This review article aims to shed light on the recent advances and future trajectories of therapeutic endoscopy, focusing on pivotal areas such as third space endoscopy, endoscopic resection techniques, artificial endoscopy, endoscopic ultrasound (EUS), the integration of artificial intelligence (AI), and endoscopic anti-reflux therapies.

Multimodal treatment with endoscopic ablation and systemic therapy for cholangiocarcinoma.

Cholangiocarcinoma (CCA) are primary malignancies of biliary system and usually unresectable at the time of diagnosis. As a consequence, majority of these cases are candidates for palliative care. With the advances in chemotherapeutic agents and multidisciplinary care, the survival rate has improved in cases with inoperable malignant biliary obstruction. As a consequence, there is a need to provide effective and durable palliative care in these patients. The main role of endoscopic palliation in the vast majority of CCA includes biliary stenting for obstructive jaundice. Recent advances in the endoscopic palliation and multimodal approach appear promising in imparting durable relief of symptoms. Use of radiofrequency ablation, photodynamic therapy and intraluminal brachytherapy has been shown to improve the survival rates as well as the patency of biliary stents. Infact, intraductal ablation may act synergistically with chemotherapy by modulating tumour signalling pathways and immune microenvironment.

Tofacitinib use in ulcerative colitis: An expert consensus for day-to-day clinical practice.

Rising number of inflammatory bowel disease (IBD) cases in developing countries necessitate clear guidance for clinicians for the appropriate use of advanced therapies. An expert consensus document was generated to guide the usage of tofacitinib, a Janus kinase inhibitor, in ulcerative colitis. Tofacitinib is a useful agent for the induction and maintenance of remission in ulcerative colitis. It can be used in the setting of biological failure or even steroid-dependent and thiopurine refractory disease. Typically, the induction dose is 10 mg BD orally. Usually, clinical response is evident within eight weeks of therapy. In those with clinical response, the dose can be reduced from 10 mg BD to 5 mg BD. Tofacitinib should be avoided or used cautiously in the elderly, patients with cardiovascular co-morbidity, uncontrolled cardiac risk factors, previous thrombotic episodes and those at high risk for venous thrombosis or previous malignancy. Baseline evaluation should include testing for and management of hepatitis B infection and latent tuberculosis. Where feasible, it is prudent to ensure complete adult vaccination, including Herpes zoster, before starting tofacitinib. The use of tofacitinib may be associated with an increased risk of infections such as herpes zoster and tuberculosis reactivation. Maternal exposure to tofacitinib should be avoided during pre-conception, pregnancy, and lactation. There is emerging evidence of tofacitinib in acute severe colitis, although the exact positioning (first-line with steroids or second-line) is uncertain.

Migrated lumen-apposing stent trapped within a pancreatic fluid collection: Forward-view EUS for the rescue!

Video 1Migrated lumen-apposing stent trapped within a pancreatic fluid collection: forward-view EUS for the rescue!

Predictors of persistent pain after extracorporeal shockwave lithotripsy for painful chronic calcific pancreatitis.

BACKGROUND: Extracorporeal shockwave lithotripsy (ESWL) and/or endoscopic retrograde cholangiopancreatography (ERCP) are recommended as first-line therapy for painful uncomplicated chronic pancreatitis with obstructed main pancreatic duct (MPD) in the pancreas head/body. However, predictors of pain relief after ESWL are unknown. We evaluated independent predictors of persistent pain in patients who underwent ESWL for chronic pancreatitis. METHODS: 640 consecutive adult patients with chronic pancreatitis, who underwent successful ESWL with ERCP and pancreatic duct (PD) stent placement, were followed for 12 months. The pain was assessed at baseline and at 12 months using the Izbicki Pain Score, with a score decrease of >50% considered pain relief. Independent predictors of pain relief were derived from logistic regression analysis. RESULTS: Of 640 patients (mean age 36.71 [SD 12.19] years; 60.5% men), 436 (68.1%) had pain relief and 204 (31.9%) had persistent pain. On univariate analysis, older age, male sex, alcohol and tobacco intake, longer duration of symptoms, dilated MPD and MPD stricture were associated with persistent pain at 12 months (P<0.05). Consumption of alcohol (odds ratio [OR] 1.93, 95%CI 1.26-2.97), tobacco (OR 4.09, 95%CI 2.43-6.90), duration of symptoms (OR 1.02, 95%CI 1.01-1.04), MPD size (OR 1.22, 95%CI 1.11-1.33), and MPD stricture (OR 8.50, 95%CI 5.01-14.42) were independent predictors of persistent pain. CONCLUSIONS: Alcohol, tobacco, duration of symptoms, MPD size and stricture were independent predictors of persistent pain after successful ESWL. A multidisciplinary team approach that includes behavioral therapy and surgical options should be considered for such patients.

Device-assisted endoscopic full-thickness resection in colorectum: Systematic review and meta-analysis.

OBJECTIVES: Endoscopic full-thickness resection (EFTR) is emerging as an effective modality for mucosal and submucosal lesions in the colorectum. In this systematic review and meta-analysis, we aimed to analyze the success and safety of device-assisted EFTR in the colon and rectum. METHODS: A literature search was performed in the Embase, PubMed, and Medline databases for studies evaluating device-assisted EFTR between inception to October 2022. The primary outcome of the study was clinical success (R0 resection) with EFTR. Secondary outcomes included technical success, procedure duration, and adverse events. RESULTS: In all, 29 studies with 3467 patients (59% male patients, 3492 lesions) were included in the analysis. The lesions were located in right colon (47.5%), left colon (28.6%), and rectum (24.3%). EFTR was performed for subepithelial lesions in 7.2% patients. The pooled mean size of the lesions was 16.6 mm (95% confidence interval [CI] 14.9-18.2, I2 98%). Technical success was achieved in 87.1% (95% CI 85.1-88.9%, I2 39%) procedures. The pooled rate of en bloc resection was 88.1% (95% CI 86-90%, I2 47%) and R0 resection was 81.8% (95% CI 79-84.3%, I2 56%). In subepithelial lesions, the pooled rate of R0 resection was 94.3% (95% CI 89.7-96.9%, I2 0%). The pooled rate of adverse events was 11.9% (95% CI 10.2-13.9%, I2 43%) and major adverse events requiring surgery was 2.5% (95% CI 2.0-3.1%, I2 0%). CONCLUSION: Device-assisted EFTR is a safe and effective treatment modality in cases with adenomatous and subepithelial colorectal lesions. Comparative studies are required with conventional resection techniques, including endoscopic mucosal resection and submucosal dissection.

Role of Novel Motorized Enteroscopy in the Evaluation of Small Bowel Diseases: A Systematic Review and Meta-analysis.

BACKGROUND AND AIM: Motorized spiral enteroscopy (MSE) has recently been introduced for small bowel evaluation. In this systematic review and meta-analysis, we aim to evaluate the safety and efficacy of MSE for evaluation of small bowel diseases. METHODS: A literature search was performed in Embase, PubMed, Medline databases for studies evaluating MSE between January -2010 and October-2022. The primary outcome of the study was diagnostic yield with MSE. Secondary outcomes included technical success, procedure duration, depth of maximum insertion (DMI), rate of pan-enteroscopy and adverse events. RESULTS: 10 studies with 961 patients [581 (60.5%) males] were included in the analysis. 1068 MSE procedures were performed by antegrade route in 698, retrograde route in 215 and bidirectional in 155 patients. Technical success was achieved in 94.9% (95% CI 92.9% to 96.4%) procedures. The pooled diagnostic yield of MSE was 73.7% (95% CI 70.7% to 76.4%). Pooled rate of pan-enteroscopy by antegrade route was 21.9% (95% CI 18.1% to 26.1%), retrograde route was 6.9% (95% CI 2.4% to 18.3%) and combined route was 61.2% (95% CI 52.4% to 69.3%). Pooled rate of major adverse events was 1.9% (95% CI 1.2% to 3.2%). CONCLUSIONS: MSE is a safe and effective tool for evaluating small bowel disorders. High diagnostic yield and low rate of adverse events make it a potential alternative to balloon enteroscopy. However, comparative trials are required in the future.

Single-use accessories and endoscopes in the era of sustainability and climate change-A balancing act.

Gastrointestinal (GI) endoscopy is among the highest waste generator in healthcare facilities. The major reasons include production of large-volume non-renewable waste, use of single-use devices, and reprocessing or decontamination processes. Single-use endoscopic accessories have gradually replaced reusable devices over last two decades contributing to the rising impact of GI endoscopy on ecosystem. Several reports of infection outbreaks with reusable duodenoscopes raised concerns regarding the efficacy and adherence to standard disinfection protocols. Even the enhanced reprocessing techniques like double high-level disinfection have not been found to be the perfect ways for decontamination of duodenoscopes and therefore, paved the way for the development of single-use duodenoscopes. However, the use of single-use endoscopes is likely to amplify the net waste generated and carbon footprint of any endoscopy unit. Moreover, single-use devices challenge one of the major pillars of sustainability, that is, "reuse." In the era of climate change, a balanced approach is required taking into consideration patient safety as well as financial and environmental implications. The possible solutions to provide optimum care while addressing the impact on climate include selective use of disposable duodenoscopes and careful selection of accessories during a case. Other options include use of disposable endcaps and development of effective high-level disinfection techniques. The collaboration between the healthcare professionals and the manufacturers is paramount for the development of environmental friendly devices with low carbon footprint.

Re-intervention rates and symptom-free survival at 1 year after endoscopic versus surgical management of strictures in Crohn's disease: A propensity matched analysis of a prospective inflammatory bowel disease cohort.

BACKGROUND AND AIM: Resection for Crohn's disease (CD) related strictures is definitive but carries risk of morbidity, recurrence, and short bowel syndrome. On the contrary, the durability of endotherapy (ET) for CD-related strictures is questionable. Prospective comparative studies are limited. We aimed to prospectively compare the outcomes of ET in CD strictures with a case-matched surgical therapy (ST) cohort. METHODS: Patients undergoing ET or resection for primary CD strictures (symptomatic, non-traversable, < 5 cm length, n ≤ 3) between January 2021 and March 2022 in a high-volume tertiary center were compared with regard to recurrent symptoms, escalation of therapy, re-intervention, and re-operation based on propensity matched analysis. RESULTS: Fifty-nine patients [49% ET, 57.6% male, median (years): 34 (15-74)] had ≥ 12 months of follow up. Before propensity matching, cumulative re-intervention rate was significantly higher with ET [34.5% (10/29) vs 3.3% (1/30) ST, P = 0.002]. Recurrent symptoms (34.5% vs 26.7%, P = 0.42), escalation of medical therapy (27.5% vs 23.3%, P = 0.64), and re-operation (7.4% vs 3.1%, P = 0.55) were comparable. In propensity matched analysis adjusted for demographics, disease, and stricture characteristics [n = 42, 21 each, 62% male, median (years): 32 (15-60)], cumulative probability of re-intervention rates was higher in ET (28.6% vs 4.8%, P = 0.042). The cumulative probability of recurrent symptoms (ET: 33.3% vs surgery 33.3%, P = 0.93), therapy escalation (ET: 23.8% vs surgery 28.6%, P = 0.75), and re-operation (ET: 9.5% vs surgery 4.8%, P = 0.57) was similar. CONCLUSIONS: ET for CD strictures require higher re-interventions compared with resection although re-operation could be avoided in the majority with comparable symptom free survival at 1 year.