Do Patients With NASH-related Cirrhosis Have Better Overall Survival Compared With Other Etiologies of Cirrhosis? A Population-based Study.

GOALS AND BACKGROUND: Nonalcoholic steatohepatitis (NASH) is a leading cause of cirrhosis. We aim to explore the clinical outcomes of NASH cirrhosis compared with other etiologies of cirrhosis. METHODS: We utilized an EHR-based database (TriNetX) to study the outcomes of NASH cirrhosis. Patients diagnosed with NAFLD or NASH and cirrhosis between January 2016 and December 2019 were identified utilizing appropriate ICD-10-CM codes. The primary outcome was 3-year overall survival. Secondary outcomes were decompensated cirrhosis, hepatocellular carcinoma, and liver transplantation. The Control group was patients with other etiologies of cirrhosis than NASH. Study and control groups were matched for demographic characters and comorbidities using propensity score matching. RESULTS: We identified 45,063 patients with NASH cirrhosis. The NASH cirrhosis cohort comprised older (61 vs. 59 y) White (78% vs. 64%) women (58% vs. 38%) with more comorbidities (diabetes mellitus, obesity, ischemic heart disease, history of cancer, chronic kidney disease). After propensity score matching, patients with NASH cirrhosis had a better 3-year survival (78% vs. 74%, HR 0.79, 95% CI 0.77-0.82) compared with patients with non-NASH cirrhosis. Hepatocellular carcinoma was diagnosed less commonly in patients with NASH cirrhosis (6.7% vs. 10.6%, P<0.001), and liver transplantation was performed more often for NASH cirrhosis compared with non-NASH cirrhosis [Risk ratio 1.13 (1.08-1.18)]. CONCLUSIONS: Patients with NASH cirrhosis probably have better 3-year overall survival than other etiologies of cirrhosis. This is an interesting finding, as patients with NASH are older and have more comorbidities. Improved survival can be partly explained by a higher probability of liver transplantation and improvements in cardiovascular outcomes.

ACUTE VENOUS THROMBOEMBOLISM IS COMMON FOLLOWING ACUTE NECROTIZING PANCREATITIS AND IS ASSOCIATED WITH WORSE CLINICAL OUTCOMES.

OBJECTIVES: While splanchnic vein thrombosis (SVT) is a well-known local complication of acute pancreatitis, extra-splanchnic VTE (ESVT) is inadequately studied. Here, we aim to explore the incidence of VTE in acute necrotizing pancreatitis (ANP) and the associated mortality. METHODS: This is a retrospective cohort study utilizing an electronic health record database. Adults with a diagnosis of ANP from January 2017 to December 2022 were identified using appropriate ICD-10-CM codes. The primary outcome was development of acute ESVT within one month of ANP. Secondary outcomes were 90-day mortality, 30-day rehospitalization, and oral anticoagulant (OAC) use in patients with ESVT. Propensity score matching (1:1) was performed for baseline characteristics and common comorbidities. RESULTS: 17,942 (7.11%) patients were diagnosed with ANP during the study period and about 10% (1,737) of them had a diagnosis of ESVT. Of all VTE, 61% were ESVT with or without SVT, and 63% (N = 1,799) were SVT. 90-day mortality (16.3% vs. 5.7%, risk ration, RR 2.86 [95% CI 2.29-3.56]) and 30-day rehospitalization (31% Vs 19%, RR 1.63 [95% CI 1.49-1.79]) were higher in patients with ESVT compared to non-VTE patients. 60% of patients with ESVT were on OAC and OAC use was associated with lower 90-day mortality (8.9% vs. 19.4%, RR 0.46) without increased risk of adverse events, like - acute gastrointestinal bleeding, intracranial bleeding, or need for packed red cell transfusion. CONCLUSIONS: Systemic VTE is common in patients with ANP and may contribute to increased mortality and risk of readmissions. Prospective studies can confirm our findings and explore the role of aggressive VTE prophylaxis in patients with ANP during hospital stay, and in the immediate ambulatory period.

Incidence and risk factors for recurrence of ampullary adenomas after endoscopic papillectomy: Comparative analysis of familial adenomatous polyposis and sporadic ampullary adenomas in an international multicenter cohort.

OBJECTIVES: Endoscopic papillectomy (EP) is a minimally invasive therapy for the management of ampullary adenomas (AA). We conducted this multicenter study to assess the incidence of and factors related to the recurrence of AA after EP in patients with familial adenomatous polyposis (FAP) compared to sporadic AA. METHODS: We included patients who underwent EP for AA at 10 tertiary hospitals. Adenomatous tissue at the resection site at the time of surveillance endoscopies was considered recurrent disease. RESULTS: In all, 257 patients, 100 (38.9%) with FAP and 157 (61%) patients with sporadic AA, were included. Over a median of 31 (range, 11-61) months, recurrence occurred in 48/100 (48%) of patients with FAP and 58/157 (36.9%) with sporadic AA (P = 0.07). Two (2%) FAP patients and 10 (6.3%) patients with sporadic AA underwent surgery for recurrence. On multivariable regression analysis, the recurrence in FAP was higher than in sporadic patients after the first year of follow-up. AA size (hazard ratio [HR] 1.03, 95% confidence interval [CI] 1.001, 1.056), periampullary extension (HR 2.5, 95% CI 1.5, 4.01), and biliary duct dilation (HR 2.04, 95% CI 1.2, 3.4) increased the risk, while en bloc resection (HR 0.6, 95% CI 0.41, 0.9) decreased the risk of recurrence. CONCLUSION: Recurrence rates are high after EP. Most recurrences in sporadic patients occur within the first year of follow-up, but after the first year of follow-up in patients with FAP. Recurrences are higher with larger adenomas, biliary duct dilation, and periampullary extensions, and may be mitigated by en bloc resection. These factors should be considered in decision-making with the patients.

Real-world evidence of safety and effectiveness of Barrett's endoscopic therapy.

BACKGROUND AND AIMS: Real-world data on the adverse events and the survival benefit of Barrett's endoscopic therapy (BET) are limited. The aim of this study was to examine the safety and effectiveness (survival benefit) of BET in patients with neoplastic Barrett's esophagus (BE). METHODS: An electronic health record-based database (TriNetX) was used to select patients with BE with dysplasia and esophageal adenocarcinoma (EAC) from 2016 to 2020. Primary outcome was 3-year mortality among patients with high-grade dysplasia (HGD) or EAC who underwent BET versus 2 comparison cohorts: patients with HGD or EAC who had not undergone BET and patients with GERD but no BE/EAC. Secondary outcome was adverse events (esophageal perforation, upper GI bleeding, chest pain, and esophageal stricture) after BET. To control for confounding variables, 1:1 propensity score matching was performed. RESULTS: We identified 27,556 patients with BE and dysplasia, of whom 5295 underwent BET. After propensity score matching, patients with HGD and EAC who underwent BET had significantly lower 3-year mortality (HGD risk ratio [RR], .59; 95% CI, .49-.71; EAC RR, .53; 95% CI, .44-.65) compared with corresponding cohorts who did not undergo BET (P < .001). There was no difference in median 3-year mortality between control subjects (GERD without BE/EAC) compared with patients with HGD (RR, 1.04; 95% CI, .84-1.27) who underwent BET. Finally, there was no difference in median 3-year mortality between patients who underwent BET compared with patients who underwent esophagectomy among both HGD (RR, .67; 95% CI, .39-1.14; P =.14) and EAC (RR, .73; 95% CI, .47-1.13; P = .14). Esophageal stricture was the most common adverse event (6.5%) after BET. CONCLUSIONS: Real-world, population-based evidence from this large database shows that endoscopic therapy is safe and effective for patients with BE. Endoscopic therapy is associated with a significantly lower 3-year mortality; however, it leads to esophageal strictures in 6.5% of treated patients.

Diagnosis and Management of Pancreatic Cysts: A Comprehensive Review of the Literature.

The prevalence of pancreatic cysts has been rising due to the widespread use of cross-sectional imaging (CT scan and MRI) of the abdomen. While most pancreatic cysts are benign and do not require treatment or surveillance, a significant minority are premalignant and rarely malignant. The risk stratification of these lesions is not straightforward, and individual risk assessment, cyst size, distribution, and alarming morphologic features (when present) can guide the next steps in management. Neoplastic pancreatic cysts are mucinous or non-mucinous. Endoscopic ultrasound with fine-needle aspiration is often required to classify pancreatic cysts into mucinous and non-mucinous cysts and to assess the malignant potential. Advances in endoscopic techniques (confocal laser endomicroscopy, microforceps biopsy) can provide a definitive diagnosis of pancreatic cysts in some cases; however, the use of these techniques involves a higher risk of adverse events.

Does acute pancreatitis herald pancreatic ductal adenocarcinoma? A multicenter electronic health research network study.

BACKGROUND AND OBJECTIVES: High mortality in pancreas ductal adenocarcinoma (PDAC) is related to delayed diagnosis and lack of cost-effective early detection strategies. Retrospective studies have demonstrated an association between PDAC and acute pancreatitis (AP). Herein, we explore the incidence of PDAC in patients with non-biliary and non-alcoholic AP. METHODS: A population-based, retrospective cohort study was conducted utilizing TriNetX (Cambridge, MA). Patients ≥40 years with AP (ICD-10-CM code: K85) and without biliary AP (K85.1), alcohol-induced AP (K85.2) or chronic pancreatitis (K86.0, K86.1), were identified. The primary outcome was incidence of PDAC (C25) in patients at defined intervals following AP. We compared the rate of early-stage diagnosis (stage 1-2) and surgical resection among patients with and without preceding AP. RESULTS: The incidence of PDAC ranged from 2.16% (1 year) to 3.43% (5 years). Patients with PDAC and AP in preceding year were more likely to undergo surgical resection relative to those without AP (10.1% vs. 6.3%, risk ratio 1.62: 95% confidence interval, CI 1.47-1.79). Early-stage diagnosis of PDAC was more frequent in patients with preceding AP; however, difference was insignificant (p = 0.48; 95% CI 0.64-2.58). CONCLUSION: AP is infrequently associated with PDAC and can precede a diagnosis of PDAC in a minority of patients without another known etiology of pancreatitis. Patients with a recent AP are more likely to undergo surgical resection of PDAC and a trend toward diagnosis at an earlier stage compared to patients with PDAC and without AP. The impact of AP-related PDAC on survival is unknown.

Does Hyperlipasemia Predict Worse Clinical Outcomes in COVID-19? A Multicenter Retrospective Cohort Study.

GOAL: We aim to perform a multicenter retrospective cohort study to determine if elevated serum lipase determines clinical outcomes in patients with coronavirus disease 2019 (COVID-19). BACKGROUND: Several cases of acute pancreatitis (AP) have recently been reported in association with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Most of the evidence is based on elevated serum lipase values without objective demonstration of pancreatic inflammation or necrosis. MATERIALS AND METHODS: A population-based, multicenter, retrospective cohort study utilizing TriNetX was performed to obtain aggregated health records of ∼69 million patients from 49 health care organizations from January 1, 2020, to December 31, 2020. Adult patients (18 y and above) diagnosed with COVID-19 were identified using appropriate International Classification of Diseases, 10th Revision (ICD-10) codes and were stratified into 2 groups, with elevated (≥180 U/L) and with normal (≤80 U/L) serum lipase. The primary outcome was 30-day mortality; other outcomes were 30-day rehospitalization, need for mechanical ventilation, need for vasopressor use, acute kidney injury. RESULTS: A total of 435,731 adult patients with COVID-19 were identified, and 1406 of them had elevated serum lipase which was associated with higher 30-day mortality [risk ratio (RR)=1.53, P<0.001], risk of acute kidney injury (RR=1.5, P=0.003), and vasopressor use (RR=1.69, P<0.001) without any difference in 30-day rehospitalization (RR=0.98, P=0.54), or need for mechanical ventilation (RR=1.20, P=0.26). The negative predictive value of normal serum lipase for 3-month mortality in patients with COVID-19 was 91%. CONCLUSIONS: Patients with COVID-19 who have elevated serum lipase experience worse clinical outcomes even in the absence of AP. If these findings can be replicated in prospective studies, serum lipase can be utilized as a marker of disease severity in patients with COVID-19.

Nutritional deficiencies and predictors of mortality in diabetic and nondiabetic gastroparesis.

BACKGROUND: Gastroparesis is a debilitating condition that may impact morbidity and mortality, but there is a lack of long-term studies examining this relation. The aim of this study was to determine the predictors of mortality in gastroparesis and to determine the nutritional deficiencies. METHODS: Between September 30, 2009 and January 31, 2020, we identified 320 patients (mean age 47.5±5.3 years, 70% female, 71.3% Whites, 39.7% diabetic and 60.3% nondiabetic) with gastroparesis. 99mTc sulfur-labeled food was used to diagnose gastroparesis. Cox proportional-hazard regression was used to compute the association of mortality predictors. RESULTS: Of the 320 patients, 46 (14.4%) died during the study period. Among diabetics, advanced age (hazard ratio [HR] 1.06, 95% confidence interval [CI] 1.03-1.10; P<0.001), chronic kidney disease (CKD) (HR 4.69, 95%CI 1.62-13.59; P=0.004), and malnutrition (HR 10.95, 95%CI 3.23-37.17; P<0.001) were associated with higher mortality, whereas in nondiabetics older age (HR 1.05, 95%CI 1.01-1.09; P=0.04), CKD (HR 10.2, 95%CI 2.48-41.99; P=0.001), chronic obstructive pulmonary disease (COPD) (HR 7.5, 95%CI 2.11-26.82; P=0.002), coronary artery disease (CAD) (HR 9.7, 95%CI 1.8-52.21; P=0.008), and malnutrition (HR 3.83, 95%CI 1.14-29.07; P=0.03) were associated with increased mortality. Overall, 48.8% had vitamin D, 18.2% had vitamin B12, and 50.8% had iron deficiencies. Only 19.4% of the whole cohort was evaluated by a nutritionist. CONCLUSIONS: Advanced age, CAD, CKD, COPD and malnutrition were associated with higher mortality in gastroparesis. Despite the high prevalence of nutritional deficiencies, consultation of a specialist nutritionist was uncommon.

Pancreatic Fungal Infection in Patients With Necrotizing Pancreatitis: A Systematic Review and Meta-analysis.

GOAL: The goal of this study was to study the incidence of fungal infection in necrotizing pancreatitis (NP) and its impact on mortality. BACKGROUND: Infected pancreatic necrosis is a major contributor to morbidity and mortality in patients with NP. While pancreatic fungal infection (PFI) has frequently been identified in patients with NP, its effect on the clinical outcomes is unclear. MATERIALS AND METHODS: A literature search was performed in Medline (Ovid), Embase (Ovid), and the Cochrane library. All prospective and retrospective studies that examined the incidence of fungal infection in NP with subgroup mortality data were included. For fungal infection of NP, studies with fungal isolation from pancreatic necrotic tissue were included. Newcastle Ottawa Scale and Joanna Briggs Institute's critical appraisal tool were used for bias assessment. RESULTS: Twenty-two studies comprising 2151 subjects with NP were included for the quantitative analysis. The mean incidence of fungal infection was 26.6% (572/2151). In-hospital mortality in the pooled sample of NP patients with PFI (N=572) was significantly higher [odds ratio (OR)=3.95, 95% confidence interval (CI): 2.6-5.8] than those without PFI. In a separate analysis of 7 studies, the mean difference in the length of stay between those with and without fungal infection was 22.99 days (95% CI: 14.67-31.3). The rate of intensive care unit admission (OR=3.95; 95% CI: 2.6-5.8), use of prophylactic antibacterials (OR=2.76; 95% CI: 1.31-5.81) and duration of antibacterial therapy (mean difference=8.71 d; 95% CI: 1.33-16.09) were all significantly higher in patients with PFI. Moderate heterogeneity was identified among the studies on estimating OR for mortality (I2=43%) between the 2 groups. CONCLUSIONS: PFI is common in patients with NP and is associated with increased mortality, intensive care unit admission rate, and length of stay. Further prospective studies are needed to better understand the pathophysiology of PFIs and to determine the role for preemptive therapeutic strategies, such as prophylactic antifungal therapy.

Genomic profiling in pancreatic ductal adenocarcinoma and a pathway towards therapy individualization: A scoping review.

CONTEXT: Pancreatic cancer (PDAC) is one of the most challenging cancers to treat with modest recent improvements in survival from new systemic therapies. There is growing interest in individualized therapy underpinned by somatic and germline genomic alterations. OBJECTIVE: A systematic review of data on therapies targeting somatic and germline alterations, and their downstream pathways in PDAC. METHOD: A systematic literature search was conducted using PRISMA guidelines to include relevant results published after January 1, 2008. RESULTS: A total of 71 relevant studies were included. We identified 36 studies targeting the KRAS-pathway, the most common being with MEK-inhibitor therapy. Twenty-two studies were identified that evaluated platinum-based chemotherapy and PARP inhibitors in patients with deleterious mutations in DNA damage repair genes and have shown encouraging results. Immunotherapy has demonstrated activity in patients with mismatch repair deficiency/microsatellite instability. CONCLUSION: Evidence from translational and clinical research presents an exciting platform for genomic targeted therapy in PDAC. Validity for targeting BRCA with platinum and PARP inhibitors and microsatellite instability with immune therapy has been established, nonetheless, evidence for targeting the common driver oncogenes is lacking and much work is needed. Of importance is identifying the subgroup of KRAS -wild type PDAC (approximately 5%) where there is enrichment for targetable opportunities.