Biflanged metal stents versus plastic stents in the endoscopic ultrasound-guided drainage of walled-off necrosis: a randomized controlled trial.

OBJECTIVE: Endoscopic ultrasound(EUS) guided drainage of walled off necrosis(WON) with either plastic stents or metal stents is the mainstay of WON management. This is a single center randomized controlled study evaluating the efficacy of bi-flanged metal stent(BFMS) and plastic stents for WON drainage. DESIGN: Patients with symptomatic WON amenable for EUS guided drainage were randomized to either BFMS or plastic stents. Primary outcome was reintervention free clinical success at 4 weeks. Secondary outcomes were overall clinical success(complete resolution of symptoms and significant reduction in size of WON (<50% of original size and <5 cm largest diameter size at 4-week follow-up)), number of re-interventions, adverse events, hospital stay for first admission and medium term outcomes at 6 months (recurrence, disconnected pancreatic duct, chronic pancreatitis and new onset diabetes mellitus). RESULTS: 92 patients were randomized - 46 in each arm. The reintervention free clinical success was significantly higher in BFMS group(67.4% vs 43.5%; P: 0.021; ITT analysis). Overall clinical success at one month was similar in both groups. There were significantly lower number of reinterventions (median 0(IQR 0-1) vs 1(0-2) P:0.028)and hospital stay duration in BFMS group(7.04 ± 3.36 days vs 9.09 ± 5.53 days; P:0.035). There was no difference in procedure-related adverse events, mortality and medium-term outcomes. CONCLUSIONS: The BFMS provides higher reintervention free clinical success at 4 weeks with shorter hospital stay without increased risk of adverse events compared to plastic stents for EUS-guided drainage of WON. Medium term outcomes are however similar in both BFMS, and plastics stents.

Early Diagnosis and Prevention of Infections in Cirrhosis.

Strategies to prevent infection and improve outcomes in patients with cirrhosis. HAV, hepatitis A virus; HBV, hepatitis B virus; COVID-19, novel coronavirus disease 2019; NSBB, nonselective ß-blocker; PPI, proton pump inhibitors.Cirrhosis is a risk factor for infections. Majority of hospital admissions in patients with cirrhosis are due to infections. Sepsis is an immunological response to an infectious process that leads to end-organ dysfunction and death. Preventing infections may avoid the downstream complications, and early diagnosis of infections may improve the outcomes. In this review, we discuss the pathogenesis, diagnosis, and biomarkers of infection; the incremental preventive strategies for infections and sepsi; and the consequent organ failures in cirrhosis. Strategies for primary prevention include reducing gut translocation by selective intestinal decontamination, avoiding unnecessary proton pump inhibitors' use, appropriate use of ß-blockers, and vaccinations for viral diseases including novel coronavirus disease 2019. Secondary prevention includes early diagnosis and a timely and judicious use of antibiotics to prevent organ dysfunction. Organ failure support constitutes tertiary intervention in cirrhosis. In conclusion, infections in cirrhosis are potentially preventable with appropriate care strategies to then enable improved outcomes.

Impact of transmural plastic stent on recurrence of pancreatic fluid collection after metal stent removal in disconnected pancreatic duct: a randomized controlled trial.

BACKGROUND: Disconnected pancreatic duct (DPD) after development of walled-off necrosis (WON) predisposes to recurrent (peri)pancreatic fluid collection (PFC). In this randomized controlled trial, we compared plastic stents with no plastic stent after removal of a large-caliber metal stent (LCMS) on incidence of recurrent PFCs in DPD. METHODS : Consecutive patients with WON who underwent endoscopic ultrasound (EUS)-guided drainage with LCMS between September 2017 and March 2020 were screened for eligibility. At LCMS removal (4 weeks after drainage), patients with DPD were randomized to plastic stent or no stent groups. The primary outcome was incidence of recurrent PFC at 3 months. Secondary outcomes were technical success of plastic stent deployment, adverse events, stent migration, and recurrence of PFC at 6 and 12 months. RESULTS: 236 patients with WON underwent EUS-guided drainage using LCMS, and 104 (males 94, median age 34 years (interquartile range [IQR] 26-44.7) with DPD were randomized into stenting (n = 52) and no-stenting (n = 52) groups. Plastic stent deployment was successful in 88.5 %. Migration occurred in 19.2 % at median follow-up of 8 months (IQR 2.5-12). Recurrent PFCs occurred in six patients at 3 months (stent n = 3, no stent n = 3). There was no significant difference in PFC recurrence between the two groups at 3, 6, and 12 months. Reintervention was required in seven patients with recurrent PFCs, with no significant difference between the two groups. CONCLUSION: In patients with WON and DPD, deployment of plastic stents after LCMS removal did not reduce recurrence of PFC.

Early liver transplantation after COVID-19 infection: The first report.

COVID-19 (coronavirus disease 2019) has impacted solid organ transplantation (SOT) in many ways. Transplant centers have initiated SOT despite the COVID-19 pandemic. Although it is suggested to wait for 4 weeks after COVID-19 infection, there are no data to support or refute the timing of liver transplant after COVID-19 infection. Here we describe the course and outcomes of COVID-19-infected candidates and healthy living liver donors who underwent transplantation. A total of 38 candidates and 33 potential living donors were evaluated from May 20, 2020 until October 30, 2020. Ten candidates and five donors were reverse transcriptase-polymerase chain reaction (RT-PCR) positive for severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) pretransplant. Four candidates succumbed preoperatively. Given the worsening of liver disease, four candidates underwent liver transplant after 2 weeks due to the worsening of liver disease and the other two candidates after 4 weeks. Only one recipient died due to sepsis posttransplant. Three donors underwent successful liver donation surgery after 4 weeks of COVID-19 infection without any postoperative complications, and the other two were delisted (as the candidates expired). This report is the first to demonstrate the feasibility of elective liver transplant early after COVID-19 infection.

Asia-Pacific consensus recommendations for endoscopic and interventional management of hilar cholangiocarcinoma.

Hilar cholangiocarcinoma (HCCA) is one of the most common types of hepatobiliary cancers reported in the world including Asia-Pacific region. Early HCCA may be completely asymptomatic. When significant hilar obstruction develops, the patient presents with jaundice, pale stools, dark urine, pruritus, abdominal pain, and sometimes fever. Because no single test can establish the definite diagnosis then, a combination of many investigations such as tumor markers, tissue acquisition, computed tomography scan, magnetic resonance imaging/magnetic resonance cholangiopancreatography, endoscopic ultrasonography/intraductal ultrasonography, and advanced cholangioscopy is required. Surgery is the only curative treatment. Unfortunately, the majority of HCCA has a poor prognosis due to their advanced stage on presentation. Although there is no survival advantage, inoperable HCCA managed by palliative drainage may benefit from symptomatic improvement. Currently, there are three techniques of biliary drainage which include endoscopic, percutaneous, and surgical approaches. For nonsurgical approaches, stent is the most preferred device and there are two types of stents i.e. plastic and metal. Type of stent and number of stent for HCCA biliary drainage are subjected to debate because the decision is made under many grounds i.e. volume of liver drainage, life expectancy, expertise of the facility, etc. Recently, radio-frequency ablation and photodynamic therapy are promising techniques that may extend drainage patency. Through a review in the literature and regional data, the Asia-Pacific Working Group for hepatobiliary cancers has developed statements to assist clinicians in diagnosing and managing of HCCA. After voting anonymously using modified Delphi method, all final statements were determined for the level of evidence quality and strength of recommendation.

Prophylactic Perioperative Terlipressin Therapy for Preventing Acute Kidney Injury in Living Donor Liver Transplant Recipients: A Systematic Review and Meta-Analysis.

Background: Acute kidney injury (AKI) is common in the perioperative transplant period and is associated with poor outcomes. Few studies reported a reduction in AKI incidence with terlipressin therapy by counteracting the hemodynamic alterations occurring during liver transplantation. However, the effect of terlipressin on posttransplant outcomes has not been systematically reviewed. Methods: A comprehensive search of electronic databases was performed. Studies reporting the use of terlipressin in the perioperative period of living donor liver transplantation were included. We expressed the dichotomous outcomes as risk ratio (RR, 95% confidence interval [CI]) using the random effects model. The primary aim was to assess the posttransplant risk of AKI. The secondary aims were to assess the need for renal replacement therapy (RRT), vasopressors, effect on hemodynamics, blood loss during surgery, hospital and intensive care unit (ICU) stay, and in-hospital mortality. Results: A total of nine studies reporting 711 patients (309 patients in the terlipressin group and 402 in the control group) were included for analysis. Terlipressin was administered for a mean duration of 53.44 ± 28.61 h postsurgery. The risk of AKI was lower with terlipressin (0.6 [95% CI, 0.44-0.8]; P = 0.001). However, on sensitivity analysis including only four randomized controlled trials (I2 = 0; P = 0.54), the risk of AKI was similar in both the groups (0.7 [0.43-1.09]; P = 0.11). The need for RRT was similar in both the groups (0.75 [0.35-1.56]; P = 0.44). Terlipressin therapy reduced the need for another vasopressor (0.34 [0.25-0.47]; P < 0.001) with a concomitant rise in mean arterial pressure and systemic vascular resistance by 3.2 mm Hg (1.64-4.7; P < 0.001) and 77.64 dyne cm-1.sec-5 (21.27-134; P = 0.007), respectively. Blood loss, duration of hospital/ICU stay, and mortality were similar in both groups. Conclusions: Perioperative terlipressin therapy has no clinically relevant benefit.

Double tunnel technique reduces technical failure during POEM in cases with severe submucosal fibrosis.

Background and study aims Submucosal fibrosis (SMF) is one of the major reasons for technical failure during per-oral endoscopic myotomy (POEM). In this study, we aimed to evaluate the impact of double tunnel technique (DT-POEM) on the technical success of POEM in cases with severe SMF. Patients and methods Data from patients with achalasia in whom SMF was encountered during POEM from Jan 2013 to Jan 2020 at our center were retrospectively evaluated. The technical success and adverse events (AEs) were analyzed and compared between cases with SMF who underwent POEM via single tunnel versus DT-POEM technique. Results A total of 1,150 patients underwent POEM during the study period. There were 14 technical failures (1.2 %). SMF and severe SMF was found in 104 (9 %) and 21 (1.8 %) patients, respectively. The majority of patients (17, 80.9 %) with severe SMF had type I achalasia. Overall, technical failures occurred in 14 cases (1.2 %) and severe SMF resulted in the majority of the technical failures (10, 71.4 %). DT-POEM was utilized in 11 cases (52.4 %) with severe SMF. The median procedure time with DT-POEM was 150 minutes (85-210). There were no major AEs and DT-POEM was technically successful in all the patients. The technical success of POEM in cases with SMF improved after the adoption of the double tunnel technique (98.4 % vs 68.3 %, P  = 0.0001). Conclusions Severe SMF is the most common reason for technical failure during POEM. DT-POEM improves the technical success rates of POEM in patients with severe SMF.

International, multicenter retrospective trial comparing the efficacy and safety of bi-flanged versus lumen-apposing metal stents for endoscopic drainage of walled-off pancreatic necrosis.

BACKGROUND: To compare fully covered bi-flanged metal stents (BFMS) and lumen-apposing metal stents (LAMS) for endoscopic ultrasound (EUS)-guided drainage/debridement of pancreatic walled-off necrosis (WON). METHODS: Patients with WON managed by EUS-guided therapy were divided into those who underwent: 1) drainage using BFMS; and 2) drainage using LAMS and scheduled direct endoscopic necrosectomy (DEN). Clinical success (resolution of the WON), technical success (successful stent placement), and adverse events (AEs) were evaluated. RESULTS: 387 patients underwent WON endoscopic drainage, 205 using BFMS and 182 using LAMS. The clinical success in the BFMS or LAMS groups were similar (197 [96.1%] vs. 174 [95.6%]; P=0.81). Median number of procedures required for WON resolution was significantly lower in BFMS compared to LAMS (2 vs. 3, P<0.001). Technical success for stent placement was similar in BFMS and LAMS groups (203 [99%] vs. 180 [99%], P=0.90). Procedure-related AEs were similar in the BFMS and LAMS groups (19 [9.3%] vs. 20 [10.9%], P=0.61). Stent dysfunction with occluding debris was higher in the BFMS group compared to LAMS group (21 [10.2 %] vs. 11 [5.9%], P=0.04). The migration rate was higher in the BFMS group than in the LAMS group (15 [7.3%] vs. 3 [1.6%]; P<0.001). DEN was required in 23 [11.2%] patients in the BFMS group after lack of WON resolution by conservative means. CONCLUSION: BFMS with a "step-up approach" and LAMS with scheduled DEN are both safe and effective for EUS-guided drainage/debridement of WON.

Endoscopic vs. Surgical Interventions for Painful Chronic Pancreatitis: What is Needed for Future Clinical Trials.

The treatment of painful chronic pancreatitis remains controversial. The available evidence from two randomized controlled trials favor surgical intervention, whereas an endotherapy-first approach is widely practiced. Chronic pancreatitis is complex disease with different genetic and environmental factors, different pain mechanisms and different treatment modalities including medical, endoscopic, and surgical. The widely practiced step-up approach remains unproven. In designing future clinical trials there are some important pre-requisites including a more comprehensive pain assessment tool, the optimization of conservative medical treatment and interventional techniques. Consideration should be given to the need of a control arm and the optimal timing of intervention. Pending better designed studies, the practical way forward is to identify subgroups of patients who clearly warrant endotherapy or surgery first, and to design the future clinical trials for the remainder.

Successful closure of spontaneous esophageal perforation (Boerhaave's syndrome) by endoscopic clipping.

Endoscopic clips have been used mainly for control of gastrointestinal (GI) bleeding and occasionally for closure of GI perforations. However, closure of spontaneous esophageal perforation (Boerhaave's syndrome) by clipping has not been reported. We described successful non-surgical closure of spontaneous esophageal perforation by endoscopic clipping in a patient with bilateral pyopneumothorax and septicemia.

Unusual locations of pseudo aneurysms as a sequel of chronic pancreatitis.

In patients with chronic pancreatitis, an actively bleeding pseudo aneurysm can be life threatening. Common sites of pseudoaneurysms are splenic, gastro-duodenal, superior & inferior pancreaticoduodenal arterial branches. Angioembolisation is an effective alternative to a complex and morbid operative management. Here we report 4 cases of unusual sites of pseudoaneurysms as a complication of pancreatitis, involving superior mesenteric and inferior phrenic arteries. Successful angioembolisation using glue and coil was achieved in 3 patients where as one underwent surgery. Technical success was 100% with the combination approach, though one patient died from multiorgan failure. This short case series reiterates the importance of vascular complications in pancreatitis at rare sites and also timely combined radiological and surgical approach for ensuring favorable outcome.

Impact of reducing duodenobiliary reflux on biliary stent patency: an in vitro evaluation and a prospective randomized clinical trial that used a biliary stent with an antireflux valve.

BACKGROUND: The mechanisms leading to occlusion of plastic biliary stents (PBS) are not known. OBJECTIVE: To evaluate the impact of reducing duodenobiliary reflux on stent patency rate. DESIGN: A newly designed antireflux PBS (AR-PBS) was tested in vitro by using ox bile. A prospective randomized trial in human beings was conducted. SETTING: Tertiary medical center. PATIENTS: Patients with malignant bile-duct strictures were studied. INTERVENTIONS: A PBS or an AR-PBS stent was placed by using standard techniques, and the patients were followed at regular intervals. Patients presenting with stent occlusion underwent re-stent placement with either a PBS or a metal stent. MAIN OUTCOME MEASUREMENTS: In vitro: resistance to retrograde flow and comparison of the basal and peak antegrade flow pressures between the 2 stents. In vivo: stent patency rates, complications, and the efficacy of the stents in improving the liver test. RESULTS: The AR-PBS stent could withstand a retrograde pressure gradient of >320 mm Hg compared with <1 mm Hg for the PBS. Secondary to the siphon effect of the valve, the antegrade flow resistance offered by the AR-PBS was on the negative side for all flow rates compared with PBS (P < .001). The median patency of the AR-PBS in human studies was 145 days (range, 52-252 days) compared with 101 days (range, 41-210 days) for the PBS (P = .002). Both stents were equally effective in improving the liver test, and complication rates were similar in the 2 groups. LIMITATIONS: The occluded stents were not examined microscopically. CONCLUSIONS: The antireflux biliary stent remains patent for a longer time and hence duodenobiliary reflux may be contributing to stent occlusion.

Safety and efficacy of the M2A patency capsule for diagnosis of critical intestinal patency: results of a prospective clinical trial.

BACKGROUND AND AIM: The presence of a critical intestinal stricture is a contraindication for conventional capsule endoscopy for the risk of impaction. Prior assessment of intestinal patency can substantially minimize this risk. The aim of the present study was to assess the safety and efficacy of the M2A patency capsule (PC) for verification of intestinal strictures. METHODS: The M2A PC consists of a biodegradable body surrounding a small radiofrequency identification (RFID) tag. This capsule was administered to patients with known or suspected intestinal strictures. Patency was verified if the capsule was excreted intact. The capsule disintegrated into small fragments and only the RFID tag was excreted if retained at the stricture beyond a stipulated time. The patency scanner was used to detect the RFID tag externally. The M2A video capsule (VC) was administered to patients who excreted the intact capsule. RESULTS: Twenty-six patients with known or suspected intestinal strictures were administered the M2A PC. This included 16 (61%) patients with tuberculosis, eight (31%) with Crohn's disease, and one each of postoperative and malignant strictures. Eight capsules were excreted intact within 72 h and two at 109 and 110 h. Fifteen capsules disintegrated in the G(I) tract and one capsule was removed during surgery. No PC-related complications were noted. Six of the eight patients who tested positive for patency were tested with the regular M2A VC with normal excretion. CONCLUSION: The M2A PC is a reliable indicator of functional patency in suspected or even known cases of intestinal stricture. It could be used prior to conventional capsule endoscopy to predict and minimize the risk of impaction.