Incidence, severity, and mortality of post-ERCP pancreatitis: an updated systematic review and meta-analysis of 145 randomized controlled trials.

BACKGROUND AND AIMS: The incidence, severity, and mortality of post-ERCP pancreatitis (PEP) largely remain unknown with changing trends in ERCP use, indication, and techniques. We sought to determine the incidence, severity, and mortality of PEP in consecutive and high-risk patients based on a systemic review and meta-analysis of patients in placebo and no-stent arms of randomized control trials (RCTs). METHODS: The MEDLINE, Embase, and Cochrane databases were searched from the inception of each database to June 2022 to identify full-text RCTs evaluating PEP prophylaxes. The incidence, severity, and mortality of PEP from the placebo or no-stent arms of RCTs were recorded for consecutive and high-risk patients. A random-effects meta-analysis for a proportions model was used to calculate PEP incidence, severity, and mortality. RESULTS: One hundred forty-five RCTs were found with 19,038 patients in the placebo or no-stent arms. The overall cumulative incidence of PEP was 10.2% (95% confidence interval [CI], 9.3-11.3), predominantly among the academic centers conducting such RCTs. The cumulative incidences of severe PEP and mortality were .5% (95% CI, .3-.7) and .2% (95% CI, .08-.3), respectively, across 91 RCTs with 14,441 patients. The cumulative incidences of PEP and severe PEP were 14.1% (95% CI, 11.5-17.2) and .8% (95% CI, .4-1.6), respectively, with a mortality rate of .2% (95% CI, 0-.3) across 35 RCTs with 3733 patients at high risk of PEP. The overall trend for the incidence of PEP among patients randomized to placebo or no-stent arms of RCTs has remained unchanged from 1977 to 2022 (P = .48). CONCLUSIONS: The overall incidence of PEP is 10.2% but is 14.1% among high-risk patients based on this systematic review of placebo or no-stent arms of 145 RCTs; this rate has not changed between 1977 and 2022. Severe PEP and mortality from PEP are relatively uncommon.

Impact of genetic testing and smoking on the distribution of risk factors in patients with recurrent acute and chronic pancreatitis.

OBJECTIVE: The aim of the present study is to assess the impact of smoking dose and duration on the distribution of risk factor(s) in patients with RAP and CP, and the impact of genetic testing on the distribution of risk factor(s) in patients with idiopathic RAP and CP. METHODS: All adult patients with RAP and CP referred to a multidisciplinary pancreatitis clinic between 2010 and 2017 were evaluated. Risk factors included alcohol and smoking, hypertriglyceridemia, biliary, and other etiologies. Genetic testing was only pursued in patients with idiopathic RAP or CP. RESULTS: Among the 1770 patients evaluated, 167 had RAP and 303 had CP. After genetic testing and smoking, the most common risk factors for RAP and CP were pathogenic variant(s) (23%) and the combination of alcohol and smoking (23%), respectively. Genetic testing and smoking assessment decreased the proportion of patients with alcoholic RAP from 17% to 5%, alcoholic CP from 33% to 10%, idiopathic RAP from 49% to 12%, and idiopathic CP from 54% to 14%. Pathogenic CFTR variants were the most common variant in patients with RAP (51%) and CP (43%). Among the 68 patients with pancreas divisum, other risk factor(s) were identified in 72%. CONCLUSION: Genetic testing and a detailed assessment of smoking dose and duration reduce the proportion of patients with alcoholic and idiopathic pancreatitis. Other risk factor(s) for pancreatitis are found in the majority of patients with pancreas divisum further questioning its role as an independent risk factor.1. What is the current knowledge?Approximately 30% of patients with pancreatitis have no clear risk factor(s) and are categorized as having an idiopathic etiology.Pathogenic variant(s) as well as smoking dose and duration are well-established risk factors for recurrent acute and chronic pancreatitis but are not widely recognized or incorporated into clinical practice.2. What is new here?Genetic testing and a detailed assessment of smoking dose and duration reduced the proportion of patients with alcoholic and idiopathic acute recurrent and chronic pancreatitis.Approximately three-fourths of patients with pancreas divisum have a risk factor for pancreatitis.

Risk factors and outcomes for bowel ischemia after open and endovascular abdominal aortic aneurysm repair.

OBJECTIVE: Bowel ischemia (BI) is a serious complication after abdominal aortic aneurysm (AAA) repair. We sought to identify the incidence and risk factors associated with the development of postoperative BI and the post-BI outcomes for patients undergoing open aortic repair (OAR) and endovascular aortic repair (EVAR) of AAAs. METHODS: A retrospective analysis was conducted for all patients who had undergone OAR or EVAR from 2003 to 2017 using the Vascular Quality Initiative database. Univariate (Student's t test, χ2, median) and multivariable (logistic regression) analyses were used to identify independent factors associated with postoperative BI and compare the post-BI in-hospital outcomes and mortality. RESULTS: We identified 45,474 patients who had undergone infrarenal AAA repair (OAR, 21.5%; EVAR, 78.5%). The overall incidence of postoperative BI was 1.9% (OAR, 6.2% vs EVAR, 0.8%; P < .001). OAR was associated with a threefold increased odds of BI compared with EVAR (adjusted odds ratio [aOR], 3.24; 95% confidence interval [CI], 2.49-4.22; P < .001). The independent factors associated with BI after OAR included older age (aOR per year of age, 1.02; 95% CI, 1.00-1.03), congestive heart failure (aOR, 1.44; 95% CI, 1.05-1.98), and ruptured aneurysm (aOR, 4.16; 95% CI, 2.98-5.81; P < .01 for all). We also found that transfusion ≥1 U (aOR, 1.69; 95% CI, 1.30-2.20), a transperitoneal approach (aOR, 2.13; 95% CI, 1.03-1.87), supraceliac clamping (aOR, 1.58; 95% CI, 1.08-2.33), and inferior mesenteric artery reimplantation (aOR, 1.41; 95% CI, 1.06-1.89) were associated with greater odds of BI after OAR (P < .01 for all). Similarly, we found that ruptured aneurysms, a longer operative time, and transfusion of ≥1 U of blood were associated with BI after EVAR (P < .001 for all). For both OAR and EVAR, the postoperative stay (median, 13 days [interquartile range (IQR), 7-26 days] vs 7 days [IQR, 5-10 days] and 11 days [IQR, 4-23 days] vs 1 day [IQR, 1-3 days], respectively) and 30-day mortality (35.0% vs 6.4% and 40.5% vs 1.9%, respectively) were significantly higher for patients with BI (P < .001 for all). The predictors of mortality for patients with BI were surgical management (aOR, 2.05; 95% CI, 1.28-3.30), older age (aOR, 1.05; 95% CI, 1.02-1.07), symptomatic aneurysm (aOR, 1.26; 95% CI, [0.60-2.62), ruptured aneurysm (aOR, 2.23; 95% CI, 1.43-3.48), longer operative time (aOR, 1.11; 95% CI, 1.01-1.22), and postoperative renal complications (aOR, 2.98; 95% CI, 1.80-4.96; P < .05 for all). CONCLUSIONS: Confirming the results from previous studies, we found that BI is more common after a ruptured aneurysm and OAR. Other associated intraoperative factors included a transperitoneal approach, supraceliac clamping, and a reimplanted inferior mesenteric artery. More than one third of patients who developed postoperative BI in our cohort had died within 30 days after AAA repair. The factors associated with mortality after BI included surgical management and postoperative renal failure. A high index of suspicion for the signs and symptoms of BI should be maintained postoperatively for patients presenting with the risk factors identified.

Association between statin use and perioperative mortality after aortobifemoral bypass in patients with aortoiliac occlusive disease.

OBJECTIVE: The benefit of statins in reducing perioperative cardiovascular events in patients undergoing suprainguinal bypass is still controversial. The purpose of this study was to evaluate the association between statin use and perioperative mortality in patients undergoing aortobifemoral bypass (ABFB) for aortoiliac occlusive disease. METHODS: We retrospectively analyzed all patients who had ABFB in the American College of Surgeons National Surgical Quality Improvement Program data set from 2011 to 2016. Univariable (t-test, χ2 test, or Fisher exact test) and multivariable logistic regression analyses were used to compare patients' characteristics and the primary outcome (30-day mortality) between statin users and nonstatin users. Propensity score matching between statin users and nonusers was also performed on the basis of variables that were different between the two groups. RESULTS: A total of 4445 patients underwent ABFB. Of those, 3032 (68.2%) were taking statins. Compared with nonstatin users, statins users were older (median [interquartile range], 67 years [59-74 years] vs 63 years [56-72 years]; P < .01) and more likely to be diabetic (31% vs 16%) and hypertensive (84% vs 63%) and to have a history of chronic obstructive pulmonary disease (20% vs 17%; all P < .05). Statin users had lower rates of 30-day mortality (3.4% vs 4.7%; P = .03) and renal complications (2.5% vs 3.7%; P = .04) compared with nonstatin users. After adjustment for patients' demographics (age, sex, race), comorbidities (diabetes, hypertension, congestive heart failure, chronic obstructive pulmonary disease, chronic kidney disease, dialysis, bleeding disorder), smoking, clinical presentation (claudication vs critical limb ischemia), and elective surgery status, statin use was associated with 32% reduction in 30-day mortality (odds ratio, 0.68; 95% confidence interval, 0.47-0.96; P = .03). Propensity score matching showed similar results (odds ratio, 0.63; 95% confidence interval, 0.41-0.95; P = .03). CONCLUSIONS: This is the largest study to date demonstrating an association between preoperative statin use and lower 30-day mortality after ABFB for aortoiliac occlusive disease. This study highlights an area of potential quality improvement as one-third of the patients undergoing this procedure are not receiving statins.

Thyroidectomy in older adults: an American College of Surgeons National Surgical Quality Improvement Program study of outcomes.

BACKGROUND: The growth of the US geriatric population coupled with the rise in thyroid nodular disease and cancer will result in an increased number of thyroidectomies performed in older adults. We aim to evaluate outcomes after thyroidectomy in older adults as compared with younger adults. METHODS: A retrospective cohort study using the American College of Surgeons National Surgical Quality Improvement Program database from 2012-2015 categorized thyroidectomy patients into three age groups: 18-64 y, 65-79 y, and ≥80 y. Thirty-day perioperative outcomes were analyzed using bivariate χ2 test and multivariate logistic regression to estimate risk of outcomes. RESULTS: Our study identified 60,990 patients who underwent thyroidectomy: 47,855 (78.4%) patients between 18 and 64 y old, 11,716 (19.2%) between 65 and 79 y old, and 1419 (2.3%) ≥80 y. Compared with younger adults, patients aged ≥80 y were 2.67 times more likely to develop a complication (95% confidence interval [CI]: 2.02-3.53, P < 0.001), 1.83 times more likely to be readmitted for any reason (95% CI: 1.40-2.38, P < 0.001), 1.54 times more likely to be readmitted for a reason related to the thyroidectomy (95% CI: 1.10-2.16, P < 0.05), and 1.66 times more likely to have an extended hospital stay (95% CI: 1.44-1.91, P < 0.001). Patients aged 65-79 y were 1.40 times more likely to develop a complication (95% CI: 1.19-1.63, P < 0.001). CONCLUSIONS: Patients aged ≥65 y have significantly higher rates of overall complications. In addition, patients aged ≥80 y have higher rates of total and thyroidectomy-related readmissions and extended length of hospital stay.

Clinicopathological Distinction of Low-AFP-Secreting vs. High-AFP-Secreting Hepatocellular Carcinomas.

Ilntroduction and aims. We aimed to investigate the clinical and pathological differences between low-AFP-secreting (AFP < 20 ng/mL) and high-AFP-secreting (AFP ≥ 20 ng/mL) hepatocellular carcinomas in patients who undergo liver transplant (LT). MATERIAL AND METHODS: We evaluated 145 patients who underwent deceased donor LT for HCC from January 1, 2005 until August 1, 2015 at the Johns Hopkins Hospital. RESULTS: Median pre-LT AFP in the entire cohort was 13 ng/mL (IQR 6-59). Using serum AFP cutoff of 20 ng/mL, 61 (42%) patients had high-AFP-secreting tumors and 84 (58%) had low-AFP-secreting tumors. Patients with high-AFP-secreting tumors had larger lesions (3 cm vs. 2.4 cm, p = 0.024), and were more likely to have microvascular-invasion (36.1% vs. 20.2%, p = 0.02) and poor-differentiation (18% vs. 4.8%, p = 0.01), and tumor recurrence following LT (28% vs. 6%, p < 0.001). The 1-year, 3-year, and 5-year recurrence-free survival for patients in the low-AFP-secreting group compared to the high-AFP-secreting group were 100%, 92%, 92% vs. 81.3%, 71.3%, 68.5% respectively (p = 0.0003). CONCLUSION: AFP is a suboptimal predictor of tumor recurrence following liver transplant in HCC patients. However, it can have some value in distinguishing more aggressive forms of HCC (high-AFP-secreting) that are associated with higher tumor recurrence. Novel tumor biomarkers are needed that can enhance predicting tumor recurrence following LT based on tumor biology.

Recipient Survival among Living Donor vs. Deceased Donor Liver Transplants for Acute Liver Failure in the United States.

Objectives: Acute liver failure (ALF) is associated with high morbidity and mortality. Timely liver transplantation (LT) is the only universally accepted therapy for ALF that is non-responsive to medical therapy. Data regarding the use of living donor LT (LDLT) for this indication in the US is scarce. Materials and Methods: United Network of Organ Sharing/Organ Procurement and Transplantation Network (UNOS/OPTN) data from January 2002 to December 2020 were reviewed. Adult and pediatric recipients listed as status 1 were included. Demographics, clinical and laboratory data, and post-LT survival rates were compared for LDLT vs. DDLT recipients. Results: There were 180 LDLT (3.6%) and 4779 DDLT (96.4%) recipients with a diagnosis of ALF. The majority of recipients in the LDLT group were pediatric (n = 164, 91%) compared to the DDLT group (n = 1455, 30%), p < 0.001. In the pediatric-only group, post-LT survival was comparable between LDLT and DDLT recipients (p = 0.15). Five-year post-LT survival was higher for pediatric recipients compared to adults in the LDLT group (84.2% vs. 62.5%, respectively, p < 0.001) and the DDLT group (82.8% vs. 78.7%, respectively, p < 0.001). Adults had a higher hazard of death compared to pediatric recipients in the LDLT group (HR = 3.560, 95% CI 1.612-7.844, p = 0.002) and the DDLT group (HR = 1.472, 95% CI 1.290-1.679, p < 0.001). In multivariate analysis results, the type of LT and age group were not associated with higher post-LT mortality. Conclusions: In the US, LDLT constitutes 3.6% of LTs for ALF. In the pediatric-only group, post-LT survival was comparable between LDLT and DDLT recipients. Overall, there were superior post-LT outcomes for pediatric recipients compared to adults for LDLT and DDLT.

Role of lower dose hepatitis B immune globulin prophylaxis in liver transplantation: A single center perspective.

Background and Aim: Prevention of hepatitis B virus (HBV) reinfection is important for long-term outcomes following liver transplantation (LT). Hepatitis B immunoglobulin (HBIG) is used among recipients who have (i) native HBV disease, (ii) hepatitis B core antibody positivity (HBcAb positivity), or (iii) received HBcAb positive organs. Nucleos(t)ide analogue (NA) monotherapy is emerging for treating patients in this setting. There is no generalized consensus on the ideal dosage of HBIG. The aim of this study was to evaluate the efficacy of low-dose HBIG (1560 international unit [IU]) for post-LT HBV prevention. Materials and Methods: HBcAb positive patients who received either HBcAb positive or hepatitis B core antibody negative (HBcAb negative) organs and HBcAb negative patients who received HBcAb positive organs between January 2016 and December 2020 were reviewed. Pre-LT HBV serologies were collected. HBV-prophylaxis strategy included NA with/without HBIG. HBV recurrence was defined as HBV deoxyribonucleic acid (DNA) positivity during the 1-year, post-LT follow-up. No HBV surface antibody titers were followed. Results: A total of 103 patients with a median age of 60 years participated in the study. Hepatitis C virus was the most common etiology. Thirty-seven HBcAb negative recipients and 11 HBcAb positive recipients with undetectable HBV DNA received HBcAb positive organs and underwent prophylaxis with 4 doses of low-dose HBIG and NA. None of the recipients in our cohort had a recurrence of HBV at 1 year. Conclusion: Low-dose HBIG (1560 IU) × 4 days and NA, for HBcAb positive recipients and HBcAb positive donors, appear to be effective in preventing HBV reinfection during the post-LT period. Further trials are needed to confirm this observation.

Factors Associated With Serial Lipase Measurement in Hospitalized Patients With Acute Pancreatitis.

OBJECTIVES: To determine the factors associated with serial lipase measurement in patients with acute pancreatitis (AP). METHODS: Patients admitted to Johns Hopkins Health System between September 2019 and August 2020 with lipase ≥3 times upper limit normal were prospectively identified. Acute pancreatitis was defined using revised Atlanta criteria. Serial lipase measurement was defined as >2 lipase measurements on consecutive days within 7 days of presentation. RESULTS: There were 294 patients with AP with mean age 52.4 ± 16 years (SD), and 155 (52.7%) were male. A total of 227 (77.2%) were admitted to a medical service. There were 111 (37.7%) who underwent serial lipase measurements. There were 89 (30.8%), 36 (12.2%), 6 (1%), and 40 (13.6%) patients with systemic inflammatory response syndrome at time of initial lipase measurement, persistent organ failure, necrosis on admission, and intensive care unit admission. Serial lipase measurements were more likely to be obtained in patients admitted to surgical services (odds ratio, 4.3; 95% confidence interval, 1.4-13.2; P = 0.01) and nontertiary hospitals (odds ratio, 1.8; 95% confidence interval, 1.0-2.9; P = 0.04). CONCLUSION: More than one-third of AP patients undergo serial lipase measurements. This practice is more likely to occur on surgical services and in nontertiary hospitals.

Frequent guidewire passage into the pancreatic duct is an independent risk factor for postendoscopic retrograde cholangiopancreatography (ERCP) pancreatitis (PEP) among high-risk individuals: A post-hoc analysis of a randomized controlled trial data.

OBJECTIVES: To systematically evaluate the patient and procedural risk factors for post-endoscopic retrograde cholangiopancreatography (ERCP) pancreatitis (PEP) among patients receiving rectal indomethacin. METHODS: Data from a randomized controlled trial (RCT) of high-risk patients undergoing ERCP who received rectal indomethacin with or without topical epinephrine was evaluated. PEP was defined based on the consensus criteria. Pancreatic stenting was excluded to avoid confounding results with the role of epinephrine spray. Multivariable logistic regression analysis was used to identify patient and procedural risk factors for PEP. RESULTS: Among 960 patients enrolled in the RCT, the PEP incidence was 6.4%. An increased risk of PEP was seen with age <50 years and female gender (odds ratio [OR] 2.40, 95% confidence interval [CI] 1.35-4.26), malignant biliary stricture(s) (OR 3.51, 95% CI 1.52-8.10), >2 guidewire passes into the pancreatic duct (PD) (OR 2.84, 95% CI 1.43-5.64), and pancreatic brush cytology (OR 6.37, 95% CI 1.10-36.90), whereas a decreased risk of PEP was seen with contrast- over guidewire-assisted cannulation (OR 0.14, 95% CI 0.02-0.99) and the use of lactated Ringer's (LR) over other fluid types (OR 0.52, 95% CI 0.27-0.98). There was a significant trend between the number of guidewire passes into the PD and PEP risk (P = 0.002). CONCLUSIONS: More than two guidewire passes into the PD and pancreatic brush cytology increased while the use of LR decreased the risk of PEP among high-risk patients receiving rectal indomethacin. Pancreatic stent placement and/or LR should be considered in patients with >2 guidewire passes into the PD.

Liver transplantation in developing countries.

With the increasing incidence and prevalence of end-stage liver disease, demand for donor grafts continues to increase. Approaches on maximizing the potential donor grafts vary depending on the region. This review aims to summarize the current practice of liver transplantation with an emphasis on challenges encountered in developing countries.

Long-Term Outcomes of Living Donor Versus Deceased Donor Liver Transplant for Hepatocellular Carcinoma in the United States.

OBJECTIVES: Although living donor liver transplant has become a vital treatment option in hepatocellular carcinoma, controversy remains on whether recurrence and survival rates are different versus deceased donor recipients. Here, we compared clinical characteristics and outcomes between recipients of living and deceased donor liver transplants for hepatocellular carcinoma in the United States. MATERIALS AND METHODS: Our comparisons used data from the United Network of Organ Sharing/Organ Procurement and Transplantation Network. RESULTS: There were 385 living donor and 25 274 deceased donor liver transplant recipients with diagnosis of hepatocellular carcinoma. Transplant list wait times of ≥6 months were more common in deceased donor(55.9%) versus living donor recipients (45.2%; P < .001). Both recipient groups were comparable with regard to alpha-fetoprotein level <200 ng/mL (P = .18). Only a small percentage in both groups had ≥3 total tumors (P = .73); both groups had similar low transplants outside of Milan criteria (P = .45). Overall, 1-, 5-, and 10-year overall survival rates for deceased versus living donor recipients were similar (91.2% vs 92%, 74% vs 76.4%, 58.9% vs 56.5%; P = .69). On multivariate analysis, Black/African American race/ethnicity was associated with worse outcomes than White race/ethnicity as reference (P < .001), whereas Hispanic and Asian race/ethnicity were more protected. Hepatitis C virus as liver disease etiology was associated with worse outcomes than other etiologies. Tumor characteristics, ≥3 lesions, tumor size, and higher alpha-fetoprotein levels were associated with worse outcomes. Living donor transplant was not associated with higher hazard of death. Among living donor recipients only, largest tumor size was associated with higher risk of death (P = .005). CONCLUSIONS: Survival was similarin between the living donor versus deceased donor recipients with hepatocellular carcinoma. With changes in Model for End-Stage Liver Disease exception policies for hepatocellular carcinoma in the United States, living donor transplant for hepatocellular carcinoma could expand the donor pool.

Sudden Cardiac Arrest Secondary to Early Repolarization Syndrome.

A healthy 41-year-old man sustained cardiac arrest secondary to ventricular fibrillation. An extensive ischemic, structural, and genetic evaluation did not identify an attributable pathologic condition. Electrocardiograms were notable for early repolarization pattern. Here we review the diagnosis, prevalence, and prognostic significance of the early repolarization syndrome on sudden cardiac death. (Level of Difficulty: Intermediate.).

Hepatocellular Carcinoma and the Role of Liver Transplantation: A Review.

Hepatocellular carcinoma (HCC) is one of the leading causes of cancer deaths worldwide and liver transplantation (LT) is the only potentially curative treatment. Over the years, Milan criteria has been used for patient selection. There is ongoing research in this field with introduction of new biomarkers for HCC that can help guide future treatment. Furthermore, newer therapies for downstaging of the tumor are being implemented to prevent dropout from the transplant list. In addition, combination therapies for better outcome are under investigation. Interestingly, the concept of living-donor LT and possible use of hepatitis C virus-positive donors has been implemented as an attempt to expand the organ pool. However, there is a conflict of opinion between different centers regarding its efficacy and data is scarce. The aim of this review article is to outline the various selection criteria for LT, discuss the outcomes of LT in HCC patients, and explore future directions of LT for HCC. Therefore, a comprehensive PubMed/MEDLINE review was conducted. To expand our search, references of the retrieved articles were also screened for additional data. After selecting the studies, the authors independently reviewed them to identify the relevant studies. After careful evaluation 120 studies relevant to out topic are cited in the manuscript. Three tables and two figures are also included. In conclusion LT for HCC has evolved over the years. With the introduction of several expanded criteria beyond Milan, the introduction of bridging therapies, such as transcatheter arterial chemoembolization and radiofrequency ablation, and the approval of newer systemic therapies, it is evident that there will be more LT recipients in the future. It is promising to see ongoing trials and the continuous evolution of protocols. Prospective studies are needed to guide the development of a pre-LT criteria that can ensure low HCC recurrence risk and is not overly stringent, clarify the role of LDLT, and determine the optimal bridging therapies to LT.

Recommendations for Hepatitis B Immunoglobulin and Antiviral Prophylaxis Against Hepatitis B Recurrence After Liver Transplantation.

The combination of hepatitis B immunoglobulin and potent nucleos(t)ide analogs after liver transplantation is considered as the standard of care for prophylaxis against hepatitis B virus recurrence. However, the recommended doses, route of administration, and duration of HBIG administration remain unclear. Moreover, hepatitis B immunoglobulin-free prophylaxis with potent nucleos(t)ide analogs has shown promising disease outcomes in preventing hepatitis B virus recurrence. The current recommendations, produced by the Turkish Association for the Study of the Liver, Acute Liver Failure and Liver Transplantation Special Interest Group, suggest a reduced need for hepatitis B immunoglobulin administration with effective long-term suppression of hepatitis B virus replication using potent nucleos(t) ide analogs after liver transplantation.

Non-steroidal anti-inflammatory drugs, intravenous fluids, pancreatic stents, or their combinations for the prevention of post-endoscopic retrograde cholangiopancreatography pancreatitis: a systematic review and network meta-analysis.

BACKGROUND: Non-steroidal anti-inflammatory drugs (NSAIDs), intravenous fluid, pancreatic stents, or combinations of these have been evaluated in randomised controlled trials (RCTs) for the prevention of post-endoscopic retrograde cholangiopancreatography (ERCP) pancreatitis, but the comparative efficacy of these treatments remains unclear. Our aim was to do an exploratory network meta-analysis of previous RCTs to systematically compare the direct and indirect evidence and rank NSAIDs, intravenous fluids, pancreatic stents, or combinations of these to determine the most efficacious method of prophylaxis for post-ERCP pancreatitis. METHODS: We searched PubMed, Embase, and the Cochrane Central Register from inception to Nov 15, 2020, for full-text RCTs that evaluated the efficacy of NSAIDs, pancreatic stents, intravenous fluids, or combinations of these for post-ERCP pancreatitis prevention in adult (aged ≥18 years) patients undergoing ERCP. Summary data from intention-to-treat analyses were extracted from published reports. We analysed incidence of post-ERCP pancreatitis across studies using network meta-analysis under the frequentist framework, obtaining pairwise odds ratios (ORs) and 95% CIs. We used the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) system for the confidence rating. This study is registered with PROSPERO, CRD42020172606. FINDINGS: We identified 1503 studies, of which 55 RCTs evaluating 20 interventions in 17 062 patients were included in the network meta-analysis. The mean incidence of post-ERCP pancreatitis in the placebo or active control group was 12·2% (95% CI 11·4-13·0). Normal saline plus rectal indometacin (OR 0·02, 95% CI 0·00-0·40), intramuscular diclofenac 75 mg (0·24, 0·09-0·69), intravenous high-volume Ringer's lactate plus rectal diclofenac 100 mg (0·30, 0·16-0·55), intravenous high-volume Ringer's lactate (0·31, 0·12-0·78), 5-7 Fr pancreatic stents (0·35, 0·26-0·48), rectal diclofenac 100 mg (0·36, 0·25-0·52), 3 Fr pancreatic stents (0·47, 0·26-0·87), and rectal indometacin 100 mg (0·60, 0·50-0·73) were all more efficacious than placebo for preventing post-ERCP pancreatitis in pairwise comparisons. 5-7 Fr pancreatic stents (0·59, 0·41-0·84), intravenous high-volume Ringer's lactate plus rectal diclofenac 100 mg (0·49, 0·26-0·94), intravenous standard-volume normal saline plus rectal indometacin 100 mg (0·04, 0·00-0·66), and rectal diclofenac 100 mg (0·59, 0·40-0·89) were more efficacious than rectal indometacin 100 mg. The GRADE confidence rating was low to moderate for 98·3% of the pairwise comparisons. INTERPRETATION: This systematic review and network meta-analysis summarises the available literature on NSAIDs, pancreatic stents, intravenous fluids, or combinations of these for prophylaxis of post-ERCP pancreatitis. Rectal diclofenac 100 mg is the best performing rectal NSAID in this network meta-analysis. Combinations of prophylaxis might be more effective, but there is little evidence. These findings help to establish prophylaxis of post-ERCP pancreatitis for future research and practice, and could reduce costs and increase adoption of prophylaxis. FUNDING: None.

Endoscopic intervention in pancreatitis: perspectives from a gastroenterologist.

The last decade has seen a dramatic paradigm shift for the treatment of pancreatitis and its related complications away from surgery to minimally invasive endoscopic approaches. In this review, we provide an overview of the indications, techniques and outcomes of endoscopic interventions in the management of acute and chronic pancreatitis. Emphasis is placed on drainage of pancreatic pseudocysts and treatment of pain in chronic pancreatitis.

From cirrhosis to hepatocellular carcinoma: An investigation into hepatitis C viral oncogenesis.

Background and Aim: Hepatitis C is a leading cause of chronic liver disease and hepatocellular carcinoma (HCC). Understanding the evolution and biology of HCC among HCV patients may lead to novel therapeutic avenues and risk stratification. Material and Methods: Using meta-analysis platform STARGEO, we performed two separate meta-analyses as follows: 357 HCV-related HCC tumor samples with 220 adjacent non-tumor samples and 92 HCV-related cirrhotic liver samples with 53 healthy liver samples as a control. Then, we analyzed the signature in Ingenuity Pathway Analysis. Results: HCV cirrhosis analysis demonstrated LPS/IL-1 mediated inhibition of RXR function, LXR/RXR activation, sirtuin signaling, IL-10 signaling and hepatic fibrosis/stellate cell activation as top canonical pathways. IL1ß, TNF, and TGF-ß1 were top upstream regulators. Cellular morphologic and signaling changes were noted through the up-regulation of RGS1/2, WNT receptor FZD7, the TGF-ß1-induced gap junction gene GJA1, and the zinc finger transcription factor repressor SNAI2. Apoptosis was inhibited through the down-regulation of OMA1. Metabolic dysfunction was noted through the down-regulation of SCLY and CBS. HCV-related HCC analysis showed FXR/RXR and LXR/RXR signaling, LPS/IL1-mediated inhibition of RXR activation, and melatonin degradation as top canonical pathways. Conclusion: Our results suggest that the genetic changes in the setting of chronic HCV infection predispose patients to developing HCC.

Recurrence of hepatocellular carcinoma following deceased donor liver transplantation: case series.

AIM: We aimed to study the clinical and pathological characteristics of liver transplant recipients with hepatocellular carcinoma recurrence. METHODS: We reviewed the data for 26 patients who had tumor recurrence after deceased donor liver transplant for hepatocellular carcinoma at the Johns Hopkins Hospital from January 2005 to December 2015. RESULTS: In total, 88% of recipients were males. The mean age was 59 years. On explant, poor differentiation was detected in 43%, while 73% had microvascular invasion. Overall, 62% were diagnosed to be outside of Milan criteria. Out of these, 15% met the criteria for downstaging. Twenty (77%) patients had pre-transplant alpha fetoprotein levels ≥ 20 ng/mL. In 54% of patients, the location of hepatocellular carcinoma (HCC) recurrence was extrahepatic, followed by intrahepatic in 31% and both intra- and extrahepatic in 15%. The post-transplant tumor recurrence was diagnosed at a mean of 427 days (range 34-1502). Fifty percent of HCC recurrences were diagnosed within one year following liver transplant. Twenty (77%) patients received treatment for their recurrent HCC: external radiation (n = 10), surgical resections (n = 8; brain 4, spine 2, bone 1, and Whipple surgery 1), sorafenib (n = 7), locoregional therapy (n = 5). Overall, 24 out of 26 (92%) recipients died within four years after the transplant. CONCLUSION: HCC recurrence after liver transplant is infrequent. More than fifty percent of HCC recurrences following liver transplant are extrahepatic. Despite better recipient selection for liver transplant, the curative options are limited in recurrent cases and associated with extremely poor outcomes.