Venous Thrombosis in Acute Pancreatitis: What to and Not to Do?

Acute pancreatitis is an acute inflammatory condition of the pancreas that has not only local but systemic effects as well. Venous thrombosis is one such complication which can give rise to thrombosis of the peripheral vasculature in the form of deep vein thrombosis, pulmonary embolism, and splanchnic vein thrombosis. The prevalence of these complications increases with the severity of the disease and adds to the adverse outcomes profile. With better imaging and awareness, more cases are being detected, although many at times it can be an incidental finding. However, it remains understudied and strangely, most of the guidelines on the management of acute pancreatitis are silent on this aspect. This review offers an overview of the incidence, pathophysiology, symptomatology, diagnostic work-up, and management of venous thrombosis that develops in AP.

Endoscopic ultrasound-guided radiofrequency ablation of pancreatic insulinoma: a state of the art review.

INTRODUCTION: Insulinomas are the most common functional pancreatic neuroendocrine tumors (PNETs) that lead to incapacitating hypoglycemia. Guidelines recommend surgical resection as the mainstay of management. However, surgery is fraught with complications, causing significant peri/post-operative morbidity. Since insulinomas are usually benign, solitary, small (<2 cm), and do not need lymphadenectomy, hence, in this regard, endoscopic ultrasound-guided radiofrequency ablation (EUS-RFA) is now being increasingly performed, to circumvent these adverse events and impairment of pancreatic function. AREAS COVERED: A comprehensive literature search was undertaken across various databases (PubMed/MEDLINE, Embase, Scopus), with no language restriction, for relevant articles (case series, reviews, case reports) pertaining to EUS-RFA for insulinoma and PNETs, till October 2023. In this review, we have explicated the role of EUS-RFA for insulinoma management, detailing thoroughly its mechanism of action, EUS-RFA devices with data on its safety and efficacy, and an algorithmic approach for its management. EXPERT OPINION: EUS-RFA is being advocated as a 'mini-invasive' option with the potential to replace surgery as a first-line approach for benign, sporadic, solitary, and small (<2 cm) insulinomas. Under real-time guidance, EUS-RFA has immense precision, is safe, predictable, with acceptable safety profile. Presently, it is being frequently performed for high-risk or inoperable candidates. Current need-of-the-hour is a randomized controlled trial to substantiate its role in the therapeutic algorithm for insulinoma management.

Lumen-apposing metal stents for the treatment of pancreatic and peripancreatic fluid collections and bleeding risk: a propensity matched study.

INTRODUCTION: Endoscopic ultrasound (EUS)-guided drainage of symptomatic pancreatic fluid collections (PFCs) using the Hot-Axios device has recently been associated with a significant risk of bleeding. This adverse event (AE) seems to occur less frequently with the use of a different device, the Spaxus stent. The aim of the current study was to compare the rates of bleeding between the two stents. METHODS: Patients admitted for treatment of PFCs by EUS plus lumen-apposing metal stent in 18 endoscopy referral centers between 10 July 2019 and 28 February 2022 were identified and their outcomes compared using a propensity-matching analysis. RESULTS: 363 patients were evaluated. After a 1-to-1 propensity score match, 264 patients were selected (132 per group). The technical and clinical success rates were comparable between the two groups. Significantly more bleeding requiring transfusion and/or intervention occurred in the Hot-Axios group than in the Spaxus group (6.8% vs. 1.5%; P = 0.03); stent type was a significant predictor of bleeding in both univariate and multivariate regression analyses (P = 0.03 and 0.04, respectively). Bleeding necessitating arterial embolization did not however differ significantly between the two groups (3.0% vs. 0%; P = 0.12). In addition, the Hot-Axios was associated with a significantly higher rate of overall AEs compared with the Spaxus stent (9.8% vs. 3.0%; P = 0.04). CONCLUSION: Our study showed that, in patients with PFCs, bleeding requiring transfusion and/or intervention occurred significantly more frequently with use of the Hot-Axios stent than with the Spaxus stent, although this was not the case for bleeding requiring embolization.

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.

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.

Buprenorphine Versus Diclofenac for Pain Relief in Acute Pancreatitis: A Double-Blinded Randomized Controlled Trial.

BACKGROUND: Although both nonsteroidal anti-inflammatory drugs (NSAIDs) and opioids are used for analgesia in acute pancreatitis (AP), the analgesic of choice is not known. We compared buprenorphine, an opioid, and diclofenac, an NSAID, for analgesia in AP. METHODS: In a double-blind randomized controlled trial, AP patients were randomized to receive intravenous diclofenac or intravenous buprenorphine. Fentanyl was used as rescue analgesia, delivered through a patient-controlled analgesia pump. Primary outcome was the difference in the dose of rescue fentanyl required. Secondary outcomes were the number of effective and ineffective demands of rescue fentanyl, pain-free interval, reduction in visual analogue scale (VAS) score, adverse events, and organ failure development. RESULTS: Twenty-four patients were randomized to diclofenac and 24 to buprenorphine. The 2 groups were matched at baseline. The total amount of rescue fentanyl required was significantly lower in the buprenorphine group:130 µg, interquartile range (IQR), 80-255 vs 520 µg, IQR, 380-1065 (P < .001). The number of total demands was 32 (IQR, 21-69) in the diclofenac arm vs 8 (IQR, 4-15) in the buprenorphine arm (P < .001). The buprenorphine group had more prolonged pain-free interval (20 vs 4 hours; P < .001), with greater reduction in the VAS score at 24, 48, and 72 hours compared with the diclofenac group. These findings were confirmed in the subgroup of moderately severe/severe pancreatitis. Adverse events profile was similar in the 2 groups. CONCLUSIONS: Compared with diclofenac, buprenorphine appears to be more effective and equally safe for pain management in AP patients, even in the subcohort of moderately severe or severe pancreatitis (Trial Registration number: CTRI/2020/07/026914).

The role of endoscopy in malignant hilar obstruction.

Malignant hilar biliary obstruction (MHO) is a medical challenge as regards both forming a correct diagnosis and its adequate management, in terms of treatment alternatives and palliative options. Surgical resection is the only curative treatment for the underlying disease, but the majority of patients are not suitable candidates because of an unresectable tumor or poor performance status. Biliary drainage (BD) can be achieved through the percutaneous transhepatic route or endoscopically, and the choice depends on a host of factors, including biliary anatomy and comorbidity of the patient. Though there is no consensus, the endoscopic approach is usually preferred over the former. Endoscopy can aid in both diagnosis (collection of histological as well as cytological samples, direct visualization of suspected malignant pathology, or use of endoscopic ultrasound [EUS] for evaluation and locoregional staging), and in achieving internal BD. Advances in the development of various stents, accessories and, more recently, the use of EUS have in fact further expanded its application in MHO management. The choice of stents to be used (type, make, and number), palliation methods, deployment techniques and the use of local ablative strategy are still evolving and require more data. The complexity of management of MHO mandates that each patient should receive a "personalized approach", all the way from establishing a diagnosis until final treatment, with the help of a multidisciplinary team effort. Herein, we provide a comprehensive literature review of the current role of endoscopy for MHO, according to its applications in various clinical settings.

EUS-guided coil and glue injection versus endoscopic glue injection for gastric varices: International multicentre propensity-matched analysis.

BACKGROUND: Gastric varices (GVs) are conventionally managed with endoscopic cyanoacrylate (E-CYA) glue injection. Endoscopic ultrasound (EUS)-guided therapy using combination of coils and CYA glue (EUS-CG) is a relatively recent modality. There is limited data comparing the two techniques. METHODOLOGY: This international multicentre study included patients with GV undergoing endotherapy from two Indian and two Italian tertiary care centres. Patients undergoing EUS-CG were compared with propensity-matched E-CYA cases from a cohort of 218 patients. Procedural details such as amount of glue, number of coils used, number of sessions required for obliteration, bleeding after index procedure rates and need for re-intervention were noted. RESULTS: Of 276 patients, 58 (male 42, 72.4%; mean age-44.3 ± 12.1 years) underwent EUS-CG and were compared with 118 propensity-matched cases of E-CYA. In the EUS-CG arm, complete obliteration at 4 weeks was noted in 54 (93.1%) cases. Compared to the E-CYA cohort, EUS-CG arm showed significantly lower number of session (1.0 vs. 1.5; p < 0.0001) requirement, lower subsequent-bleeding episodes (13.8% vs. 39.1%; p < 0.0001) and lower re-intervention (12.1% vs. 50.4%; p < 0.001) rates. On multivariable regression analysis, size of the varix (aOR-1.17; CI 1.08-1.26) and technique of therapy (aOR-14.71; CI 4.32-50.0) were significant predictors of re-bleeding. A maximum GV size >17.5 mm had a 69% predictive accuracy for need for re-intervention. CONCLUSION: Endoscopic ultrasound-guided therapy of GV using coil and CYA glue is a safe technique with better efficacy and lower re-bleeding rates on follow-up compared to the conventional endoscopic CYA therapy.

Cholangiocarcinoma in the Era of Immunotherapy.

Cholangiocarcinoma (CCA) is a rare malignancy of the gastrointestinal tract, with aggressive behavior, and portends a poor prognosis. Traditionally, it is classified according to its site of involvement as intrahepatic, perihilar, and distal cholangiocarcinoma. A host of genetic and epigenetic factors have been involved in its pathogenesis. Chemotherapy has remained the standard first-line treatment over the last decade, with a disappointing median overall survival of 11 months for locally advanced and metastatic CCA. The advent of immunotherapy has revolutionized the treatment of many pancreaticobiliary malignancies, offering durable responses with a safe therapeutic profile. To date, there have been no significant advances in the management of CCA. Novel immunotherapeutic methods, such as cancer vaccines, adoptive cell therapy, and combinations of immune checkpoint inhibitors with other agents, are currently under investigation and may improve prognosis with overall survival. Efforts to find robust biomarkers for response to treatment along with multiple clinical trials are also ongoing in this regard. In this review, we present an overview of the current advances and the future perspectives of immunotherapy in the management of CCA.

Endoscopic ultrasound-guided vascular interventions: An expanding paradigm.

Endoscopic ultrasound (EUS) has expanded its arena from a mere diagnostic modality to an essential therapeutic tool in managing gastrointestinal (GI) diseases. The proximity of the GI tract to the vascular structures in the mediastinum and the abdomen has facilitated the growth of EUS in the field of vascular interventions. EUS provides important clinical and anatomical information related to the vessels' size, appearance and location. Its excellent spatial resolution, use of colour doppler with or without contrast enhancement and ability to provide images "real-time" helps in precision while intervening vascular structures. Additionally, structures such as venous collaterals or varices can be dealt with optimally using EUS. EUS-guided vascular therapy with coil and glue combination has revolutionized the management of portal hypertension. It also helps to avoid radiation exposure in addition to being minimally invasive. These advantages have led EUS to become an upcoming modality to complement traditional interventional radiology in the field of vascular interventions. EUS-guided portal vein (PV) access and therapy is a new kid on the block. EUS-guided portal pressure gradient measurement, injecting chemotherapy in PV and intrahepatic portosystemic shunt has expanded the horizons of endo-hepatology. Lastly, EUS has also forayed into cardiac interventions allowing pericardial fluid aspiration and tumour biopsy with experimental data on access to valvular apparatus. Herein, we provide a comprehensive review of the expanding paradigm of EUS-guided vascular interventions in GI bleeding, portal vein access and its related therapeutic interventions, cardiac access, and therapy. A synopsis of all the technical details involving each procedure and the available data has been tabulated, and the future trends in this area have been highlighted.

Same-session double EUS-guided bypass versus surgical gastroenterostomy and hepaticojejunostomy: an international multicenter comparison.

BACKGROUND AND AIMS: Gastric outlet and biliary obstruction are common manifestations of GI malignancies and some benign diseases for which standard treatment would be surgical gastroenterostomy and hepaticojejunostomy (ie, "double bypass"). Therapeutic EUS has allowed for the creation of an EUS-guided double bypass. However, same-session double EUS-guided bypass has only been described in small proof-of-concept series and lacks a comparison with surgical double bypass. METHODS: A retrospective multicenter analysis was performed of all consecutive same-session double EUS-guided bypass procedures performed in 5 academic centers. Surgical comparators were extracted from these centers' databases from the same time interval. Efficacy, safety, hospital stay, nutrition and chemotherapy resumption, long-term patency, and survival were compared. RESULTS: Of 154 identified patients, 53 (34.4%) received treatment with EUS and 101 (65.6%) with surgery. At baseline, patients undergoing EUS exhibited higher American Society of Anesthesiologists scores and a higher median Charlson Comorbidity Index (9.0 [interquartile range {IQR}, 7.0-10.0] vs 7.0 [IQR, 5.0-9.0], P < .001). Technical success (96.2% vs 100%, P = .117) and clinical success rates (90.6% vs 82.2%, P = .234) were similar when comparing EUS and surgery. Overall (11.3% vs 34.7%, P = .002) and severe adverse events (3.8% vs 19.8%, P = .007) occurred more frequently in the surgical group. In the EUS group, median time to oral intake (0 days [IQR, 0-1] vs 6 days [IQR, 3-7], P < .001) and hospital stay (4.0 days [IQR, 3-9] vs 13 days [IQR, 9-22], P < .001) were significantly shorter. CONCLUSIONS: Despite being used in a patient population with more comorbidities, same-session double EUS-guided bypass achieved similar technical and clinical success and was associated with fewer overall and severe adverse events when compared with surgical gastroenterostomy and hepaticojejunostomy.

Dynamics of Serum Procalcitonin Can Predict Outcome in Patients of Infected Pancreatic Necrosis: A Prospective Analysis.

BACKGROUND: Timely intervention can alter outcome in patients of infected pancreatic necrosis (IPN) but lacks adequate biomarker. Role of serum procalcitonin (PCT) in the management of IPN is understudied, and hence, this study was planned. METHODOLOGY: All patients of acute pancreatitis with IPN without prior intervention were included. Baseline demographic, radiological and laboratory parameters were documented. PCT was measured at baseline, prior to intervention, and thereafter every 72 h. Patients were grouped into those having baseline PCT < 1.0 ng/mL and those with PCT ≥ 1.0 ng/mL and various outcome measures were compared. RESULTS: Of the 242 patients screened, 103 cases (66 males; 64.1%) with IPN were grouped into 2: PCT < 1.0 ng/mL (n = 29) and PCT ≥ 1.0 ng/mL (n = 74). Patients with baseline PCT ≥ 1.0 ng/mL had significantly more severe disease scores. 16 out of 19 patients with rise in PCT on day-7 post-intervention expired. PCT ≥ 1.0 ng/mL group had higher need for ICU (p = 0.001) and mortality (p = 0.044). PCT > 2.25 ng/mL (aOR 22.56; p = 0.013) at baseline and failure in reduction of PCT levels to < 60% of baseline at day-7 post-intervention (aOR 53.76; p = 0.001) were significant mortality predictors. CONCLUSION: Baseline PCT > 1.0 ng/mL is associated with poor outcome. PCT > 2.25 ng/mL and failure in reduction of PCT levels to < 60% of its baseline at day-7 post-intervention can identify high-mortality risk patients.