The efficacy of Hemospray in managing bleeding related to gastrointestinal tumors: systematic review and meta-analysis.

INTRODUCTION: Gastrointestinal (GI) bleeding stemming from malignant tumors is increasingly recognized, due to advancements in oncology and detection methods. Traditional endoscopic hemostatic techniques have shown variable success rates in managing hemorrhagic GI neoplasms. Hemospray, an emerging endoscopic hemostatic powder, offers promise in treating upper GI bleeding, potentially extending its utility to neoplastic bleeding sites. This meta-analysis aims to evaluate Hemospray's efficacy in managing bleeding related to GI tumors. METHODS: We searched Embase, Scopus, Web of Science, Medline/PubMed, and Cochrane. Inclusion criteria encompassed studies focusing on malignancy-related GI bleeding and interventions utilizing Hemospray. Comparative studies contrasted Hemospray with standard endoscopic treatments (SET), while noncomparative studies assessed Hemospray's efficacy independently. The risk of bias was assessed using appropriate tools, and statistical analyses were performed using Review Manager and open Meta analyst software. RESULTS: We included 19 studies in our meta-analysis. Hemospray demonstrated higher rates of immediate hemostasis compared to SET (odds ratio: 17.14, 95% confidence interval: 4.27-68.86), with consistent outcomes across studies. Rebleeding rates at 14 and 30 days were comparable between Hemospray and SET groups, suggesting similar efficacy in long-term hemostasis. Hemospray showed a significantly lower need for nonendoscopic hemostasis compared to SET (odds ratio: 0.51, 95% confidence interval: 0.30-0.87), indicating a potential reduction in supplementary interventions. Safety assessments revealed no confirmed adverse events directly linked to Hemospray. CONCLUSION: This meta-analysis highlights Hemospray's efficacy in achieving immediate hemostasis in GI tumor-related bleeding, with potential benefits in reducing supplementary interventions and improving patient outcomes. Despite comparable rebleeding rates, Hemospray emerges as a valuable adjunctive therapy in managing malignant GI bleeding.

Case Series of SMARCA4-Deficient Undifferentiated Esophageal Carcinoma.

Undifferentiated esophageal carcinomas (UEC) are rare, with aggressive behavior and a dismal prognosis. An extremely rare subset is the SMARCA4-deficient UEC, which has only been reported in 14 cases to date. We present two cases of male patients (39- and 64-year-old) with SMARCA4-deficient UEC. Both patients had evidence of metastatic disease on presentation, progressed rapidly, and passed away within three months from the presentation. We aim to raise awareness of this underreported disease and contribute to the exploration of the possible underlying pathology and risk factors.

Clinical course of non-alcoholic fatty liver disease and the implications for clinical trial design.

BACKGROUND & AIMS: The predicted risk and timeline to progression to liver-related outcomes in the population with NAFLD are not well-characterized. We aimed to examine the risk and time to progression to cirrhosis, hepatic decompensation and death in a contemporary population over a long follow-up period, to obtain information to guide endpoint selection and sample size calculations for clinical trials on NAFLD-related cirrhosis. METHODS: This is a retrospective study of prospectively collected data in a medical record linkage system, including all adults diagnosed with NAFLD between 1996-2016 by clinical, biochemical and radiological criteria in Olmsted County, Minnesota and followed until 2019. Liver-related outcomes and death were ascertained and validated by individual medical record review. Time and risk of progression from NAFLD to cirrhosis to decompensation and death were assessed using multistate modeling. RESULTS: A total of 5,123 individuals with NAFLD (median age 52 years, 53% women) were followed for a median of 6.4 (range 1-23) years. The risk of progression was as follows: from NAFLD to cirrhosis: 3% in 15 years; compensated cirrhosis to first decompensation: 33% in 4 years (8%/year); first decompensation to ≥2 decompensations: 48% in 2 years. Albumin, bilirubin, non-bleeding esophageal varices and diabetes were independent predictors of decompensation. Among the 575 deaths, 6% were liver related. Therapeutic trials in compensated cirrhosis would require enrolment of a minimum of 2,886 individuals followed for >2 years to detect at least a 15% relative decrease in liver-related endpoints. CONCLUSION: In this population-based cohort with 23 years of longitudinal follow-up, NAFLD was slowly progressive, with liver-related outcomes affecting only a small proportion of people. Large sample sizes and long follow-up are required to detect reductions in liver-related endpoints in clinical trials. LAY SUMMARY: For patients with compensated non-alcoholic steatohepatitis-related cirrhosis, the time spent in this state and the risk of progression to decompensation are not well-known in the population. We examined the clinical course of a large population-based cohort over 23 years of follow-up. We identified that adults with compensated cirrhosis spend a mean time of 4 years in this state and have a 10% per year risk of progression to decompensation or death. The risk of further progression is 3-fold higher in adults with cirrhosis and one decompensating event. These results are reflective of placebo arm risks in drug clinical trials and are essential in the estimation of adequate sample sizes.

Natural History of Nonalcoholic Fatty Liver Disease With Normal Body Mass Index: A Population-Based Study.

BACKGROUND & AIMS: The natural history of lean nonalcoholic fatty liver disease (NAFLD) is not well-understood. Consequently, patient counseling and disease management are limited. We aimed to compare the natural history of lean, overweight, and obese NAFLD in a U.S. population with long-term follow-up. METHODS: All adults diagnosed with NAFLD in Olmsted County, MN between 1996 and 2016 were identified, and all subsequent medical events were ascertained using a medical record linkage system. Subjects were divided on the basis of body mass index (BMI) at NAFLD diagnosis into 3 groups: normal, overweight, and obese. The probability to develop cirrhosis, decompensation, malignancies, cardiovascular events, or death among the 3 groups was estimated by using the Aalen-Johansen method, treating death as a competing risk. The impact of BMI categories on these outcomes was explored by using Cox proportional hazards regression analysis. RESULTS: A total of 4834 NAFLD individuals were identified: 414 normal BMI, 1189 overweight, and 3231 obese. Normal BMI NAFLD individuals were characterized by a higher proportion of women (66% vs 47%) and lower prevalence of metabolic comorbidities than the other 2 groups. In reference to obese, those with normal BMI NAFLD had a nonsignificant trend toward lower risk of cirrhosis (hazard ratio [HR], 0.33, 95% confidence interval [CI], 0.1-1.05). There were no significant differences in the risk of decompensation (HR, 0.79; 95% CI, 0.11-5.79), cardiovascular events (HR, 1.05; 95% CI, 0.73-1.51), or malignancy (HR, 0.87; 95% CI, 0.51-1.48). Compared with obese, normal BMI NAFLD had higher risk of all-cause mortality (HR, 1.96; 95% CI, 1.52-2.51). CONCLUSIONS: NAFLD with normal BMI is associated with a healthier metabolic profile and possibly a lower risk of liver disease progression but similar risk of cardiovascular disease and malignancy than obese NAFLD.

Liver Stiffness by Magnetic Resonance Elastography Predicts Future Cirrhosis, Decompensation, and Death in NAFLD.

OBJECTIVES: Magnetic resonance elastography (MRE) is the most accurate method of liver stiffness measurement (LSM) in nonalcoholic fatty liver disease (NAFLD). We aimed to investigate the role of MRE in the prediction of hard outcomes in NAFLD. METHODS AND RESULTS: Adults with NAFLD who underwent MRE between 2007 and 2019 at Mayo Clinic, Rochester were identified. Cox regression analyses were used to explore the predictive role of baseline LSM for 1) development of cirrhosis in noncirrhotic NAFLD and 2) development of liver decompensation or death in those with compensated cirrhosis. A total of 829 NAFLD subjects (54% women, median age 58 years) were identified. Of 639 subjects without cirrhosis, 20 developed cirrhosis after a median follow-up of 4 years. Baseline LSM was predictive of future cirrhosis development: age-adjusted HR = 2.93 (95% CI, 1.86-4.62, p <.0001) per 1 kPa increment (C-statistic = 0.86). Baseline LSM by MRE can be used to guide timing of longitudinal noninvasive monitoring: 5, 3 and 1 years for LSM of 2, 3 and 4-5 kPa, respectively. Of 194 subjects with compensated cirrhosis, 81 developed decompensation or death after a median follow-up of 5 years. Baseline LSM was predictive of future decompensation or death: HR = 1.32 (95% CI, 1.13-1.56, p = .0007) per 1 kPa increment after adjusting for age, sex and MELD-Na. The 1-year probability of future decompensation or death in cirrhosis with baseline LSM of 5 kPa vs 8 kPa is 9% vs 20%, respectively. CONCLUSION: In NAFLD, LSM by MRE is a significant predictor of future development of cirrhosis. These data expand the role of MRE in clinical practice beyond the estimation of liver fibrosis and provide important evidence that improves individualized disease monitoring and patient counseling.

Extrahepatic Malignancies in Nonalcoholic Fatty Liver Disease.

Purpose of Review: Malignancy is the second most common cause of death in individuals with nonalcoholic fatty liver disease (NAFLD). Understanding unique characteristics of malignancy risk beyond hepatocellular carcinoma in NAFLD has significant implications in counseling and personalized preventative measures in this high-risk population. Herein, we systematically review the literature reporting extra-hepatic malignancies in NAFLD and discuss the key biological mechanisms underpinning the association between excess adiposity and cancer risk. Recent Findings: Several studies have shown significant associations between NAFLD and extrahepatic malignancies. The strongest association was found with cancers of the gastrointestinal tract and hormone-sensitive cancers. Recent data support sex-specific differences in cancer risk increase in NAFLD: colorectal cancer in men and uterine cancer in women. The risk of cancer development is higher in NAFLD than obesity alone. Summary: A growing body of observational evidence over the last decade supports the association between NAFLD and extrahepatic malignancies. This association requires further studies, ideally designed to include more detailed measures of body fat deposition beyond BMI in well-characterized, large cohorts of NAFLD patients, to determine if screening policies should be individualized in this group.