Endoscopic glue injection versus glue plus BRTO or TIPSS for preventing gastric variceal bleeding: A randomized controlled trial.

BACKGROUND AND AIMS: To compare the efficacy of endoscopic injection sclerotherapy with N-butyl cyanoacrylate glue (EIS-CYA) vs EIS-CYA plus a radiologic intervention (either transjugular intrahepatic portosystemic shunt (TIPSS) or balloon-occluded retrograde transvenous obliteration (BRTO)) for secondary prophylaxis in patients with liver cirrhosis who presented with acute variceal bleeding (AVB) from cardiofundal varices. Primary outcome measure was gastric varix (GV) rebleed rates at 1 year. METHODS: Consecutive cirrhosis patients with AVB from cardiofundal varices were randomized into two arms (45 in each) after primary hemostasis by EIS-CYA. In the 'endoscopic intervention' (EI) arm, EIS-CYA was repeated at regular intervals (1, 3, 6 and 12 months), while in the 'radiological intervention' (RI) arm, patients underwent TIPSS or BRTO followed by endoscopic surveillance. RESULTS: GV rebleed rates at 1 year were higher in the EI arm compared to the RI arm: 11 (24·4%; 95% CI: 12·9%-39·5%) versus 1 (2·2%; 95% CI: 0·1%-11·8%); (p=0·004) [ARD: 22.2% (95% CI: 8.4%-36.6%)]. GV rebleed related mortality in the EI arm [8 (17·8%; 95% CI: 8·0%-32·1%)] was significantly higher than in the RI arm [1 (2·2%; 0·1%-11·8%)] (p=0.030) [ARD: 15.6 (95% CI: 2.9%-29.2%)], however, there was no difference in all-cause mortality between the two groups (12 [26·7%; 95% CI: 14·6 to 41·9] versus 7 [15·6%; 95% CI: 6·5 to 29·5]). Numbers needed to treat (NNT) to prevent one GV-related rebleed at 1 year was 4.5. CONCLUSION: Radiological intervention for secondary prophylaxis reduces rebleeding from gastric varices and GV rebleeding related mortality in patients with gastric variceal hemorrhage. (CTRI/2021/02/031396).

Utility of dual-energy CT and advanced multiparametric MRI based imaging biomarkers of pancreatic fibrosis in grading the severity of chronic pancreatitis.

PURPOSE: To non-invasively quantify pancreatic fibrosis and grade severity of chronic pancreatitis (CP) on dual-energy CT (DECT) and multiparametric MRI (mpMRI). METHODS: We included 72 patients (mean age:30years; 59 men) with suspected or confirmed CP from December 2019 to December 2021 graded as equivocal(n = 20), mild(n = 18), and moderate-marked(n = 34) using composite imaging and endoscopic ultrasound criteria. Study patients underwent multiphasic DECT and mpMRI of the abdomen. Normalized iodine concentration(NIC) and fat fraction(FF) on 6-minute delayed DECT, and T1 relaxation time(T1Rt), extracellular volume fraction(ECVf), intravoxel incoherent motion-based perfusion fraction(PF), and magnetization transfer ratio(MTR) on mpMRI of pancreas were compared. 20 renal donors(for DECT) and 20 patients with renal mass(for mpMRI) served as controls. RESULTS: NIC of pancreas in controls and progressive grades of CP were 0.24 ± 0.05, 0.80 ± 0.18, 1.06 ± 0.23, 1.40 ± 0.36, FF were 9.28 ± 5.89, 14.19 ± 5.29, 17.31 ± 5.99, 29.32 ± 12.22, T1Rt were 590.11 ± 61.13, 801.93 ± 211.01, 1006.79 ± 352.18, 1388.01 ± 312.23ms, ECVf were 0.07 ± 0.03, 0.30 ± 0.12, 0.41 ± 0.12, 0.53 ± 0.13, PF were 0.38 ± 0.04, 0.28 ± 0.07, 0.25 ± 0.09, 0.21 ± 0.05 and MTR were 0.12 ± 0.03, 0.15 ± 0.06, 0.21 ± 0.07, 0.26 ± 0.06, respectively. There were significant differences for all quantitative parameters between controls and mild CP; for NIC, PF, and ECVf between controls and progressive CP grades (p < 0.05). Area under curve for NIC, FF, T1Rt, ECVf, PF, and MTR in differentiating controls and mild CP were 1.00, 0.86, 0.95, 1.00, 0.90 and 0.84 respectively and for NIC, FF, ECVf and PF in differentiating controls and equivocal CP were 1.00, 0.76, 0.95 and 0.92 respectively. CONCLUSION: DECT and mpMRI were useful in quantifying pancreatic fibrosis and grading the severity of CP. NIC was the most accurate marker.

Thromboelastography-guided vs. standard-of-care or on-demand platelet transfusion in patients with cirrhosis and thrombocytopenia undergoing procedures: A randomized controlled trial.

PURPOSE: To compare the efficacy and safety of a thromboelastography (TEG)-guided platelet transfusion strategy to empirical or on-demand transfusions in patients with cirrhosis and severe thrombocytopenia (platelet counts <50 x109/L) undergoing high-risk invasive procedures. MATERIALS AND METHODS: This was a single-center, single-blinded, randomized controlled trial. Patients with cirrhosis and severe thrombocytopenia undergoing high-risk invasive procedures were randomized into three groups- TEG group: transfusions based on TEG parameters; SOC group: 3 units of random donor platelets pre-procedure; On-demand group: transfusions based on procedural adverse effects /clinician's discretion. The primary outcome was periprocedural platelet transfusion in each arm. RESULTS: Eighty-seven patients were randomized (29 in each group) with no significant differences in demographics/coagulation profile/procedures. The median platelet count was 33 x109/L (IQR: 26-43). Percutaneous liver biopsy was the most common procedure (46, 52.9%). Significantly lower number of patients in the TEG group received platelets (4 cases, 13.8%; 95%CI: 3.9-31.7) compared to SOC (100%; 95%CI: 88.1-100) (p<0.001). Four patients in the on-demand group received platelets (13.8%; 95%CI: 3.9-31.7). Minor (WHO grade 2) procedure-related bleeding occurred in 3 (10%; 95%CI: 2.2-27.4) patients in the TEG-guided transfusion group, compared to 1 (3.4%; 95%CI: 0.1-17.8) each in SOC and on-demand groups, respectively (p=0.43) although our sample size was underpowered for comparison of outcomes such as post-procedural bleeding. No bleeding-related mortality was observed in any of the three groups. CONCLUSION: Thromboelastography-guided transfusion reduces prophylactic transfusions in patients with cirrhosis and severe thrombocytopenia undergoing high-risk invasive procedures. (CTRI/2021/05/033464).

Percutaneous Endoscopic Necrosectomy.

Patients with acute pancreatitis might develop infected necrotic fluid collections which are associated with significant morbidity and mortality. Patients with infected necrotizing pancreatitis not responding to antibiotics require drainage and subsequent necrosectomy (Step-up approach). Percutaneous endoscopic necrosectomy (PEN) has evolved as a minimally invasive approach for necrosectomy through the percutaneous catheter route using a flexible endoscope and can be done under conscious sedation. It is best suited for predominantly laterally placed infected necrotic fluid collections and also can be performed at the bedside for sick patients admitted to an ICU. PEN has a clinical success rate of 80% with minimal adverse events.

Universal prophylactic rectal nonsteroidal anti-inflammatory drugs with a policy of selective pancreatic duct stenting significantly reduce post-endoscopic retrograde cholangiopancreatography pancreatitis.

BACKGROUND: Although rectal nonsteroidal anti-inflammatory drugs (NSAIDs) have been shown to be effective for the prevention of post-ERCP (endoscopic retrograde cholangiopancreatography) pancreatitis (PEP) in high-risk patients, the benefit in average-risk patients is unclear. We aimed at assessing the benefit of prophylactic rectal NSAIDs in unselected consecutive patients to prevent PEP. METHODS: All patients undergoing index ERCP procedures from January 2018 until March 2020 were included. All patients received prophylactic rectal diclofenac. A prophylactic pancreatic duct (PD) stent was placed if there was repeated PD cannulation, at the discretion of the endoscopist. The frequency of PEP was compared with historical controls. RESULTS: Of 769 patients who underwent ERCP, 34 (4.4%) developed PEP (mild in 29 [85.3%], moderate in four [11.8%] and severe in one [2.9%]). Female gender, precut sphincterotomy, inadvertent PD cannulation and procedural time of > 30 minutes predicted PEP in univariate analysis. Inadvertent PD cannulation (OR 4.6, 95% CI: 1.8-11.7; p < 0.001) and procedural time of > 30 minutes (OR 8.5, 95% CI: 3.7-10.1; p < 0.001) were independent risk factors on multivariate analysis. When compared with historical controls, the odds of PEP with prophylactic use of rectal NSAIDs and selective PD stenting was 0.54 (CI: 0.31-0.93, p = 0.027). The number needed to treat (NNT) was 22 to prevent one PEP with prophylactic rectal NSAIDs. CONCLUSION: Routine use of prophylactic rectal NSAIDs effectively prevents the occurrence of PEP in unselected consecutive patients in a real-world scenario.

International multidisciplinary survey on the initial management of acute pancreatitis: Perspective of point-of-care specialists focused on daily practice.

BACKGROUND: The initial management of patients with acute pancreatitis impacts both morbidity and mortality. Point-of-care decisions have been reported to differ from clinical guideline recommendations. METHODS: An online anonymous questionnaire was distributed through scientific associations and social media using REDCap. Multivariable logistic regression was used to identify the characteristics of participants associated with compliance with the recommendations. RESULTS: A total of 1054 participants from 94 countries completed the questionnaire; median age (IQR) was 39 (32-47) years; 30.7% were women. Among the participants, 37% opted for nonmoderate flow of i.v. fluid, 31% for fluid type other than Ringer's lactate; 73.4% were in favor of nil per os to patients who could eat, 75.5% for other than enteral feeding to patients with oral intolerance; 15.5% used prophylactic antibiotic in patients with severe acute pancreatitis, 34.1% in necrotizing acute pancreatitis, and 27.4% in patients with systemic inflammatory response syndrome; 27.8% delayed cholecystectomy after biliary acute pancreatitis. Participants with publications in PubMed on acute pancreatitis showed better compliance (OR, 1.62; 95% CI: 1.15-2.32; P = .007) with recommendations of the clinical guidelines. CONCLUSIONS: Feeding and nutrition require the greatest improvement efforts, but also the use of prophylactic antibiotics and timing of cholecystectomy should be improved.

Epidural Analgesia for Pain Management in Acute Pancreatitis during Pregnancy and Its Effect on Maternal and Fetal Outcome.

Background: Acute pancreatitis (AP) during pregnancy is a rare presentation with an estimated incidence of 1 case per 1000 to 10,000 pregnancies. Severe epigastric and abdominal pain is the earliest and the most common symptom of AP, and adequate pain relief is an integral part of patient management. The aim of our study was to investigate the different pain relief modalities that are used in pregnant women with AP and the efficacy of each method used, in terms of better pain relief and maternal-fetal outcomes. Methods: This was a retrospective observational study over a period of 6 years conducted at a tertiary care hospital. Pregnant women with clinical and biochemical diagnoses of acute pancreatitis were included in the study. Patient's history and clinical and biochemical data were collected from the medical records of the hospital. Results: A total of 12 patients were included in the study, 5 out of 12 patients had gall stones associated with AP, 2 patients had hypertriglyceridemia, and 1 each had preeclampsia and eclampsia. Epidural analgesia at the level of L1-L2 spinal level showed a reduction of VAS scores from 8 or 9 to 1 or 2, indicating excellent pain as compared to t intravenous (i/v) infusion of fentanyl or i/v boluses of injection tramadol, in whom VAS was never reduced below 3. With satisfactory results, labour analgesia and anesthesia for caesarean section was provided via the same catheter in 2 and 3 patients, respectively. Maternal and fetal outcomes were comparable in all the patients. Conclusion: AP in pregnancy, when diagnosed early and managed accordingly, leads to better maternal and fetal outcomes. Epidural analgesia was better than intravenous analgesia in terms of pain management and better recovery of acute pancreatitis patients. In these patients, labour analgesia and anesthesia for caesarean section can be provided through the same catheter, making it a potential novel modality in the treatment of acute pancreatitis in pregnancy.

Effect of thrombocytopenia and platelet transfusion on outcomes of acute variceal bleeding in patients with chronic liver disease.

BACKGROUND: Platelet transfusion in acute variceal bleeding (AVB) is recommended by few guidelines and is common in routine clinical practice, even though the effect of thrombocytopenia and platelet transfusion on the outcomes of AVB is unclear. AIM: To determine how platelet counts, platelets transfusions, and fresh frozen plasma transfusions affect the outcomes of AVB in cirrhosis patients in terms of bleeding control, rebleeding, and mortality. METHODS: Prospectively maintained database was used to analyze the outcomes of cirrhosis patients who presented with AVB. The outcomes were assessed as the risk of rebleeding at days 5 and 42, and risk of death at day 42, considering the platelet counts and platelet transfusion. Propensity score matching (PSM) was used to compare the outcomes in those who received platelet transfusion. Statistical comparisons were done using Kaplan-Meier curves with log-rank tests and Cox-proportional hazard model for rebleeding and for 42-d mortality. RESULTS: The study included 913 patients, with 83.5% men, median age 45 years, and Model for End-stage Liver Disease score 14.7. Platelet count < 20 × 109/L, 20-50 × 109/L, and > 50 × 109/L were found in 23 (2.5%), 168 (18.4%), and 722 (79.1%) patients, respectively. Rebleeding rates were similar between the three platelet groups on days 5 and 42 (13%, 6.5%, and 4.7%, respectively, on days 5, P = 0.150; and 21.7%, 17.3%, and 14.4%, respectively, on days 42, P = 0.433). At day 42, the mortality rates for the three platelet groups were also similar (13.0%, 23.2%, and 17.2%, respectively, P = 0.153). On PSM analysis patients receiving platelets transfusions (n = 89) had significantly higher rebleeding rates on day 5 (14.6% vs 4.5%; P = 0.039) and day 42 (32.6% vs 15.7%; P = 0.014), compared to those who didn't. The mortality rates were also higher among patients receiving platelets (25.8% vs 23.6%; P = 0.862), although the difference was not significant. On multivariate analysis, platelet transfusion and not platelet count, was independently associated with 42-d rebleeding. Hepatic encephalopathy was independently associated with 42-d mortality. CONCLUSION: Thrombocytopenia had no effect on rebleeding rates or mortality in cirrhosis patients with AVB; however, platelet transfusion increased rebleeding on days 5 and 42, with a higher but non-significant effect on mortality.

Early Versus Delayed Cholecystectomy for Acute Biliary Pancreatitis: A Systematic Review and Meta-Analysis.

BACKGROUND: Recommendations regarding the timing of cholecystectomy for acute biliary pancreatitis (ABP) require a systematic summary of current evidence to guide clinical practice. We conducted a systematic review and meta-analysis of randomized controlled trials (RCTs) comparing early cholecystectomy (EC) versus delayed cholecystectomy (DC) in patients with ABP. METHODS: We searched databases Medline, Embase, SCOPUS, Web of Science and Cochrane CENTRAL for randomized controlled trials addressing this question. Pairs of reviewers abstracted data and assessed the risk of bias in included studies. A random-effects meta-analysis was done to study the effect of the timing of cholecystectomy on outcomes of interest in patients with ABP. GRADE methodology was used to rate the quality in the body of evidence for each outcome as high, moderate, low, or very low. RESULTS: 11 randomized trials (1176 participants) were included. High-quality evidence from seven RCTs (867 participants) showed a statistically significant reduction in the risk for recurrent biliary events in favour of early cholecystectomy (RR 0.10, 95% CI 0.05 to 0.19, I2 = 0%). High-quality evidence from five trials was in favour of early cholecystectomy with a significant reduction in the risk 7of recurrent pancreatitis (RAP) in comparison to delayed cholecystectomy (RR 0.21, 95% CI 0.09 to 0.51, I2 = 0%). CONCLUSION: This review showed that EC has definite advantages over DC in terms of reducing recurrent pancreaticobiliary events and LOS following mild ABP. However, more RCTs are required to study the role of EC in patients with moderately-severe and severe ABP. Trial Registration Protocol registered on Prospero (CRD42020192823).

Virus related acute pancreatitis and virus superinfection in the 'Dual disease' model of acute pancreatitis and SARS-Co-V2 infection: A multicentre prospective study.

BACKGROUND: SARS-CoV-2 can cause acute pancreatitis (AP) and SARS-CoV-2 superinfection can occur in patients with AP during prolonged hospitalisation. Our objective was to characterize SARS-CoV-2 related AP and study the impact of SARS-CoV-2 superinfection on outcomes in AP. METHODS: In this multicentre prospective study, all patients with AP and SARS-CoV-2 infection between August 2020 and February 2021 were divided into two groups: SARS-CoV-2-related AP and superadded SARS-CoV-2 infection in patients with AP. The two groups were compared with each other and the whole cohort was compared with a non-COVID AP cohort. RESULTS: A total of 85 patients with SARS-CoV-2 and AP (SARS-CoV-2-related AP; n = 18 and AP with SARS-CoV-2 superadded infection; n = 67) were included during the study period. They had a higher mortality [28 (32.9%) vs. 44 (19.1%), aOR 2.8 (95% CI, 1.5-5.3)] than 230 propensity matched non-COVID AP patients. Mortality in SARS-CoV-2 and AP patients was due to critical COVID. SARS-CoV-2-related- AP (n = 18) had a higher but statistically insignificant mortality than SARS-CoV-2 superinfection in AP [8/18 (44.4%) vs 20/67 (29.8%), p = 0.24]. On multivariable analysis, infection with SARS-CoV-2 (aHR 2.3; 95% CI, 1.43.7) was a predictor of in-hospital mortality in addition to organ failure (OF) in patients with AP. CONCLUSION: Patients with AP and SARS-CoV-2 infection had a higher mortality than matched non-COVID AP patients which was largely attributable to the severity of COVID-19. SARS-CoV-2 related AP had higher OF and in-hospital mortality.

Pancreatic hemorrhage contributes to late mortality in patients with acute necrotizing pancreatitis.

OBJECTIVES: The frequency, risk factors, and impact on survival of hemorrhage into (peri)pancreatic collections in patients with acute pancreatitis (AP) has not been well studied. The study was designed to evaluate the risk factors for hemorrhage, successful hemostasis and its effect on in-hospital mortality. METHODS: In a prospective cohort study for prediction of severity of AP, the incidence, risk factors, and outcomes of pancreatic hemorrhage were analyzed. Patients with significant hemorrhage were managed according to a predefined protocol including endovascular intervention. RESULTS: Out of 363 patients hospitalized during the study-period, 33(9%) patients developed hemorrhage. Median time from onset of AP to hemorrhage was 59(45-68) days. The cause of hemorrhage was arterial in 19(57.5%) patients and unlocalized in 14(42.5%) patients. Hemorrhage was managed by conservative approach in 7 (21.2%), radiographic angioembolisation in 16 (48.5%), radiographic angioembolisation followed by surgery in 3 (9.1%), and surgery in 7 (21.2%) patients. Persistent organ failure [aHR 2.3 (1.1-5.1), p = 0.03], use of large bore (>20 Fr) catheter for initial drainage [aHR 3.9 (1.7-9.1), p = 0.001] and extensive (>50%) necrosis [aHR 3.1 (1.4-6.9), p = 0.005] were significant risk factors for hemorrhage. Hemorrhage was an independent predictor of mortality [aHR 2.0 (1.2-3.4), p = 0.008] in addition to persistent organ failure (aHR 12.1 (5.7-25.8), p < 0.001). In-hospital mortality in patients with hemorrhage was 22/33 (66.7%) vs. 81/330 (25%) in no hemorrhage group [p <0.001]. CONCLUSION: Pancreatic hemorrhage occurs later in the course of acute pancreatitis in relatively sicker group of patients with organ failure and extensive necrosis, and is independently associated with a higher risk of in-hospital mortality.

Endoscopic transmural drainage tailored to quantity of necrotic debris versus laparoscopic transmural internal drainage for walled-off necrosis in acute pancreatitis: A randomized controlled trial.

BACKGROUND AND AIMS: Both endoscopic and laparoscopic transmural internal drainage are practiced for drainage of walled-off necrosis (WON) following acute pancreatitis (AP) but the superiority of either is not established. Our aim was to compare transperitoneal laparoscopic drainage with endoscopic drainage using either lumen apposing metal stents (LAMS) or plastic stents tailored to the amount of necrotic debris in WON. METHODS: In a randomized controlled trial, adequately powered to exclude the null hypothesis, patients with symptomatic WON were randomized to either endoscopic or laparoscopic drainage. In the endoscopy group, two plastic stents were placed if the WON contained <1/3rd necrotic debris and a LAMS was placed if it was >1/3rd. Primary outcome was resolution of WON within 4 weeks without re-intervention for secondary infection. Secondary outcome was overall success (resolution of WON at 6 months) and adverse events. RESULTS: Forty patients were randomized: 20 to each group. Baseline characteristics were comparable between the groups. Primary outcome was similar between the groups [16 (80%) in laparoscopy and 15 (75%) in endoscopy group; p = 0.89]. The overall success was similar [18 (90%) in laparoscopy vs. 17 (85%) in endoscopy; p = 0.9]. Median duration of hospital stay was shorter in endoscopy group [4 (4-8) vs. 6 days (5-9); p = 0.03]. Adverse events were comparable between the groups. CONCLUSION: Laparoscopic drainage was not superior to endoscopic transmural drainage with placement of multiple plastic stent or LAMS depending on the amount of necrotic debris for symptomatic WON in AP. The hospital stay was shorter with the endoscopic approach.