Controversies and Future Directions in Management of Acute Appendicitis: An Updated Comprehensive Review.

Globally, acute appendicitis has an estimated lifetime risk of 7-8%. However, there are numerous controversies surrounding the management of acute appendicitis, and the best treatment approach depends on patient characteristics. Non-operative management (NOM), which involves the utilization of antibiotics and aggressive intravenous hydration, and surgical appendectomy are valid treatment options for healthy adults. NOM is also ideal for poor surgical candidates. Another important consideration is the timing of surgery, i.e., the role of interval appendectomy (IA) and the possibility of delaying surgery for a few hours on index admission. IA refers to surgical removal of the appendix 8-12 weeks after the initial diagnosis of appendicitis. It is ideal in patients with a contained appendiceal perforation on initial presentation, wherein an initial nonoperative approach is preferred. Furthermore, IA can help distinguish malignant and non-malignant causes of acute appendicitis, while reducing the risk of recurrence. On the contrary, a decision to delay appendectomy for a few hours on index admission should be made based on the patients' baseline health status and severity of appendicitis. Post-operatively, surgical drain placement may help reduce postoperative complications; however, it carries an increased risk of drain occlusion, fistula formation, and paralytic ileus. Furthermore, one of the most critical aspects of appendectomy is the closure of the appendiceal stump, which can be achieved with the help of endoclips, sutures, staples, and endoloops. In this review, we discuss different aspects of management of acute appendicitis, current controversies in management, and the potential role of endoscopic appendectomy as a future treatment option.

Basic Principles and Role of Endoscopic Ultrasound in Diagnosis and Differentiation of Pancreatic Cancer from Other Pancreatic Lesions: A Comprehensive Review of Endoscopic Ultrasound for Pancreatic Cancer.

Pancreatic cancer is one of the leading causes of cancer-related deaths worldwide. Pancreatic lesions consist of both neoplastic and non-neoplastic lesions and often pose a diagnostic and therapeutic challenge due to similar clinical and radiological features. In recent years, pancreatic lesions have been discovered more frequently as incidental findings due to the increased utilization and widespread availability of abdominal cross-sectional imaging. Therefore, it becomes imperative to establish an early and appropriate diagnosis with meticulous differentiation in an attempt to balance unnecessary treatment of benign pancreatic lesions and missing the opportunity for early intervention in malignant lesions. Endoscopic ultrasound (EUS) has become an important diagnostic modality for the identification and risk stratification of pancreatic lesions due to its ability to provide detailed imaging and acquisition of tissue samples for analysis with the help of fine-needle aspiration/biopsy. The recent development of EUS-based technology, including contrast-enhanced endoscopic ultrasound, real-time elastography-endoscopic ultrasound, miniature probe ultrasound, confocal laser endomicroscopy, and the application of artificial intelligence has significantly augmented the diagnostic accuracy of EUS as it enables better evaluation of the number, location, dimension, wall thickness, and contents of these lesions. This article provides a comprehensive overview of the role of the different types of EUS available for the diagnosis and differentiation of pancreatic cancer from other pancreatic lesions while discussing their key strengths and important limitations.

Impact of frailty on endoscopic retrograde cholangiopancreatography outcomes in nonagenarians: A United States national experience.

BACKGROUND: Endoscopic retrograde cholangiopancreatography (ERCP) is an essential therapeutic tool for biliary and pancreatic diseases. Frail and elderly patients, especially those aged ≥ 90 years are generally considered a higher-risk population for ERCP-related complications. AIM: To investigate outcomes of ERCP in the Non-agenarian population (≥ 90 years) concerning Frailty. METHODS: This is a cohort study using the 2018-2020 National Readmission Database. Patients aged ≥ 90 were identified who underwent ERCP, using the international classification of diseases-10 code with clinical modification. Johns Hopkins's adjusted clinical groups frailty indicator was used to classify patients as frail and non-frail. The primary outcome was mortality, and the secondary outcomes were morbidity and the 30 d readmission rate related to ERCP. We used univariate and multivariate regression models for analysis. RESULTS: A total of 9448 patients were admitted for any indications of ERCP. Frail and non-frail patients were 3445 (36.46%) and 6003 (63.53%) respectively. Indications for ERCP were Choledocholithiasis (74.84%), Biliary pancreatitis (9.19%), Pancreatico-biliary cancer (7.6%), Biliary stricture (4.84%), and Cholangitis (1.51%). Mortality rates were higher in frail group [adjusted odds ratio (aOR) = 1.68, P = 0.02]. The Intra-procedural complications were insignificant between the two groups which included bleeding (aOR = 0.72, P = 0.67), accidental punctures/lacerations (aOR = 0.77, P = 0.5), and mechanical ventilation rates (aOR = 1.19, P = 0.6). Post-ERCP complication rate was similar for bleeding (aOR = 0.72, P = 0.41) and post-ERCP pancreatitis (aOR = 1.4, P = 0.44). Frail patients had a longer length of stay (6.7 d vs 5.5 d) and higher mean total charges of hospitalization ($78807 vs $71392) compared to controls (P < 0.001). The 30 d all-cause readmission rates between frail and non-frail patients were similar (P = 0.96). CONCLUSION: There was a significantly higher mortality risk and healthcare burden amongst nonagenarian frail patients undergoing ERCP compared to non-frail. Larger studies are warranted to investigate and mitigate modifiable risk factors.

Role of fecal microbiota transplant in management of hepatic encephalopathy: Current trends and future directions.

Fecal microbiota transplantation (FMT) offers a potential treatment avenue for hepatic encephalopathy (HE) by leveraging beneficial bacterial displacement to restore a balanced gut microbiome. The prevalence of HE varies with liver disease severity and comorbidities. HE pathogenesis involves ammonia toxicity, gut-brain communication disruption, and inflammation. FMT aims to restore gut microbiota balance, addressing these factors. FMT's efficacy has been explored in various conditions, including HE. Studies suggest that FMT can modulate gut microbiota, reduce ammonia levels, and alleviate inflammation. FMT has shown promise in alcohol-associated, hepatitis B and C-associated, and non-alcoholic fatty liver disease. Benefits include improved liver function, cognitive function, and the slowing of disease progression. However, larger, controlled studies are needed to validate its effectiveness in these contexts. Studies have shown cognitive improvements through FMT, with potential benefits in cirrhotic patients. Notably, trials have demonstrated reduced serious adverse events and cognitive enhancements in FMT arms compared to the standard of care. Although evidence is promising, challenges remain: Limited patient numbers, varied dosages, administration routes, and donor profiles. Further large-scale, controlled trials are essential to establish standardized guidelines and ensure FMT's clinical applications and efficacy. While FMT holds potential for HE management, ongoing research is needed to address these challenges, optimize protocols, and expand its availability as a therapeutic option for diverse hepatic conditions.

Early and Late Readmissions of Radiation Proctitis in the United States: Are We Getting Better?

Background/Aims: Radiation proctitis (RP), a well-known complication of pelvic radiation therapy, may lead to recurrent hospitalizations. We aimed to assess readmissions of RP in the United States. Methods: We analyzed the Nationwide Readmission Database from 2016 to 2020 to identify all 30-, 60-, and 90-day readmissions of RP in the United States. Hospitalization characteristics, predictors, clinical outcomes, and healthcare burdens were assessed. Results: From 2016 to 2020, we noted a declining trend of 30-, 60-, and 90-day readmissions of RP in the US. However, the all-cause 30-, 60-, and 90-day readmission rates of RP were still high at 13.7%, 19.4%, and 23.16%, respectively. On readmission, RP was identified as the admitting diagnosis in only 20.61%, 17.87%, and 15.76% of 30-, 60-, and 90-day readmissions, respectively. The mean age for all readmissions was 70 years with a significant male dominance. Lower endoscopy at index admission reduced the risk of readmissions within 90 days, but this was not statistically significant. However, the Charlson Comorbidity Index (CCI) score was an independent predictor of all readmissions. Furthermore, the mean length of stay was 5.57 (95% CI 5.15-6), 5.50 (95% CI 5.12-5.89), and 5.47 (95% CI 5.07-5.87) days and the mean hospitalization charge was USD 60,451 (95% CI USD 54,728-66,174), USD 62,671 (95% CI USD 57,326-68,015), and USD 62,144 (95% CI USD 57,144-67,144) for 30-, 60-, and 90-day readmissions. The all-cause inpatient mortality for 30-, 60-, and 90-day readmissions was 3.58%, 3.89%, and 3.46%, respectively. Conclusions: RP readmissions are a significant healthcare burden. Further efforts must be directed toward improving management strategies to reduce readmission rates.

The impact of COVID-19 on hospitalizations that underwent endoscopic retrograde cholangiopancreatography in the United States.

BACKGROUND/OBJECTIVES: COVID-19 impacts technical success of endoscopic retrograde cholangiopancreatography (ERCP). In this study, we aimed to assess the influence of COVID-19 on hospitalizations that underwent ERCP. METHODS: We identified all adult COVID-19 and non-COVID-19 hospitalizations that underwent ERCP in the United States using the National Inpatient Sample for 2020. Hospitalization characteristics, clinical outcomes, and complications were compared between the two groups. RESULTS: In 2020, 2015 COVID-19 and 203,094 non-COVID-19 hospitalizations underwent ERCP. The COVID-19 cohort had a higher mean age (60.3 vs 55.6 years, p < 0.001) and a higher proportion of Blacks and Hispanics compared to the non-COVID-19 cohort. After adjusting for confounders, the COVID-19 cohort had higher all-cause inpatient mortality (4.77 vs 1.45%, aOR 4.09, 95% CI 2.50-6.69, p < 0.001), mean length of stay (LOS) [10.19 vs 5.94 days, mean difference: 3.88, 95% CI 2.68-5.07, p < 0.001] and mean total hospital charges (THC) [$152,933 vs $96,398, mean difference: 46,367, 95% CI 21,776-70,957, p < 0.001] compared to the non-COVID-19 cohort. Increasing age, higher Charlson Comorbidity Index, and post-ERCP pancreatitis were identified to be independent predictors of inpatient mortality for COVID-19 hospitalizations that underwent ERCP. Furthermore, the COVID-19 cohort had higher odds of developing post-ERCP pancreatitis (PEP) (11.55 vs 7.05%, aOR 1.64, 95% CI 1.19-2.25, p = 0.002) compared to the non-COVID-19 cohort, after adjusting for confounders. However, there was no statistical difference in the rates of bowel perforations and post-ERCP hemorrhage between the two groups. CONCLUSION: COVID-19 hospitalizations that underwent ERCP had higher inpatient mortality, mean LOS, mean THC, and odds of developing PEP compared to the non-COVID-19 cohort. CLINICAL TRIAL REGISTRATION: This study is not a part of a clinical trial.

Clinical outcomes and predictors for 30-day readmissions of endoscopic retrograde cholangiopancreatography in the United States.

BACKGROUND/OBJECTIVES: We aimed to assess 30-day readmissions of endoscopic retrograde cholangiopancreatography (ERCP) in the United States. METHODS: The National Readmission Database was utilized from 2016 to 2020 to identify 30-day readmissions of ERCP. Hospitalization characteristics and outcomes were compared between index hospitalizations and readmissions. Predictors of 30-day readmission and mortality were also identified. RESULTS: Between 2016 and 2020, 885 416 index hospitalizations underwent ERCP. Of these, 88 380 (10.15%) were readmitted within 30 days. Compared to index hospitalizations, 30-day readmissions had higher mean age (63.76 vs 60.8 years, P < 0.001) and proportion of patients with Charlson Comorbidity Index (CCI) score ≥3 (48.26% vs 29.91%, P < 0.001). Sepsis was the most common readmission diagnosis. Increasing age, male gender, higher CCI scores, admissions at large metropolitan teaching hospitals, cholecystectomy on index hospitalization, biliary stenting, increasing length of stay (LOS) at index admission, post-ERCP pancreatitis, post-ERCP hemorrhage, and gastrointestinal tract perforation were independent predictors of 30-day readmissions. Furthermore, 30-day readmissions had higher odds of inpatient mortality (4.42% vs 1.66%, aOR 1.9, 95% CI: 1.79-2.01, P < 0.001) compared to index hospitalizations. However, we noted a shorter LOS (5.78 vs 6.22 days, mean difference 1.2, 95% CI: 1.12-1.28, P < 0.001) and lower total hospital charge ($71 076 vs $93 418, mean difference $31 452, 95% CI: 29 835-33 069, P < 0.001) for 30-day readmissions compared to index hospitalizations. Increasing age, higher CCI scores, increasing LOS, biliary stenting, and post-ERCP hemorrhage were independent predictors of inpatient mortality for 30-day readmissions. CONCLUSION: After index ERCP, the 30-day remission rate was 10.15%. Compared to index hospitalizations, 30-day readmissions had higher odds of inpatient mortality.

Liver transplant in primary sclerosing cholangitis: Current trends and future directions.

Primary sclerosing cholangitis (PSC) is a chronic and progressive immune-mediated cholangiopathy causing biliary tree inflammation and scarring, leading to liver cirrhosis and end-stage liver disease. Diagnosis of PSC is challenging due to its nonspecific symptoms and overlap with other liver diseases. Despite the rising incidence of PSC, there is no proven medical therapy that can alter the natural history of the disease. While liver transplantation (LT) is the most effective approach for managing advanced liver disease caused by PSC, post-transplantation recurrence of PSC remains a challenge. Therefore, ongoing research aims to develop better therapies for PSC, and continued efforts are necessary to improve outcomes for patients with PSC. This article provides an overview of PSC's pathogenesis, clinical presentation, and management options, including LT trends and future aspects. It also highlights the need for improved therapeutic options and ethical considerations in providing equitable access to LT for patients with PSC. Additionally, the impact of liver transplant on the quality of life and psychological outcomes of patients with PSC is discussed. Ongoing research into PSC's pathogenesis and post-transplant recurrence is crucial for improved understanding of the disease and more effective treatment options.

Acute pancreatitis in liver transplant hospitalizations: Identifying national trends, clinical outcomes and healthcare burden in the United States.

BACKGROUND: Acute pancreatitis (AP) in liver transplant (LT) recipients may lead to poor clinical outcomes and development of severe complications. AIM: We aimed to assess national trends, clinical outcomes, and the healthcare burden of LT hospitalizations with AP in the United States (US). METHODS: The National Inpatient Sample was utilized to identify all adult (≥ 18 years old) LT hospitalizations with AP in the US from 2007-2019. Non-LT AP hospitalizations served as controls for comparative analysis. National trends of hospitalization characteristics, clinical outcomes, complications, and healthcare burden for LT hospitalizations with AP were highlighted. Hospitalization characteristics, clinical outcomes, complications, and healthcare burden were also compared between the LT and non-LT cohorts. Furthermore, predictors of inpatient mortality for LT hospitalizations with AP were identified. All P values ≤ 0.05 were considered statistically significant. RESULTS: The total number of LT hospitalizations with AP increased from 305 in 2007 to 610 in 2019. There was a rising trend of Hispanic (16.5% in 2007 to 21.1% in 2018, P-trend = 0.0009) and Asian (4.3% in 2007 to 7.4% in 2019, p-trend = 0.0002) LT hospitalizations with AP, while a decline was noted for Blacks (11% in 2007 to 8.3% in 2019, P-trend = 0.0004). Furthermore, LT hospitalizations with AP had an increasing comorbidity burden as the Charlson Comorbidity Index (CCI) score ≥ 3 increased from 41.64% in 2007 to 62.30% in 2019 (P-trend < 0.0001). We did not find statistically significant trends in inpatient mortality, mean length of stay (LOS), and mean total healthcare charge (THC) for LT hospitalizations with AP despite rising trends of complications such as sepsis, acute kidney failure (AKF), acute respiratory failure (ARF), abdominal abscesses, portal vein thrombosis (PVT), and venous thromboembolism (VTE). Between 2007-2019, 6863 LT hospitalizations with AP were compared to 5649980 non-LT AP hospitalizations. LT hospitalizations with AP were slightly older (53.5 vs 52.6 years, P = 0.017) and had a higher proportion of patients with CCI ≥ 3 (51.5% vs 19.8%, P < 0.0001) compared to the non-LT cohort. Additionally, LT hospitalizations with AP had a higher proportion of Whites (67.9% vs 64.6%, P < 0.0001) and Asians (4% vs 2.3%, P < 0.0001), while the non-LT cohort had a higher proportion of Blacks and Hispanics. Interestingly, LT hospitalizations with AP had lower inpatient mortality (1.37% vs 2.16%, P = 0.0479) compared to the non-LT cohort despite having a higher mean age, CCI scores, and complications such as AKF, PVT, VTE, and the need for blood transfusion. However, LT hospitalizations with AP had a higher mean THC ($59596 vs $50466, P = 0.0429) than the non-LT cohort. CONCLUSION: In the US, LT hospitalizations with AP were on the rise, particularly for Hispanics and Asians. However, LT hospitalizations with AP had lower inpatient mortality compared to non-LT AP hospitalizations.

Role of Therapeutic Endoscopic Ultrasound in Management of Pancreatic Cancer: An Endoscopic Oncologist Perspective.

Pancreatic cancer is a highly lethal disease with an aggressive clinical course. Patients with pancreatic cancer are usually asymptomatic until significant progression of their disease. Additionally, there are no effective screening guidelines for pancreatic cancer in the general population. This leads to a delay in diagnosis and treatment, resulting in poor clinical outcomes and low survival rates. Endoscopic Ultrasound (EUS) is an indispensable tool for the diagnosis and staging of pancreatic cancer. In the modern era, with exponential advancements in technology and device innovation, EUS is also being increasingly used in a variety of therapeutic interventions. In the context of pancreatic cancer where therapies are limited due to the advanced stage of the disease at diagnosis, EUS-guided interventions offer new and innovative options. Moreover, due to their minimally invasive nature and ability to provide real-time images for tumor localization and therapy, they are associated with fewer complication rates compared to conventional open and laparoscopic approaches. In this article, we detail the most current and important therapeutic applications of EUS for pancreatic cancer, namely EUS-guided Fine Needle Injections, EUS-guided Radiotherapy, and EUS-guided Ablations. Furthermore, we also discuss the feasibility and safety profile of each intervention in patients with pancreatic cancer to provide gastrointestinal medical oncologists, radiation and surgical oncologists, and therapeutic endoscopists with valuable information to facilitate patient discussions and aid in the complex decision-making process.