Severity of gallstone, sludge or microlithiasis induced pancreatitis - all of the same?

BACKGROUND/AIM: Severity of microlithiasis and sludge-induced pancreatitis in comparison to gallstone-induced pancreatitis has never been studied for a lack of definition. In order to understand whether bile duct obstruction or other mechanisms contribute to biliary pancreatitis severity we performed a monocentric, retrospective cohort study. METHODS: In this retrospective cohort study 263 patients with acute biliary pancreatitis treated at a tertiary care center from 2005 to 2021 were stratified according to the recent consensus definition for microlithiasis and sludge. The gallstone-pancreatitis cohort was compared to microlithiasis, sludge and suspected stone passage pancreatitis cohorts in terms of pancreatitis outcome, liver function and EUS/ERCP results using one-way ANOVA and Chi2 test. Multinomial logistic regression analysis was performed to correct for bias. RESULTS: Microlithiasis and sludge-induced pancreatitis classified according to the revised Atlanta classification, did not present with a milder course than gallstone-induced pancreatitis (p = 0.62). Microlithiasis and sludge showed an increase in bilirubin on the day of admission to hospital, which was not significantly different from gallstone-induced pancreatitis (p = 0.36). The likelihood of detecting biliary disease on EUS resulting in bile duct clearance was highest on the day of admission and day 1, respectively. CONCLUSION: Microlithiasis and sludge induce gallstone-equivalent impaired liver function tests and induce pancreatitis with similar severity compared with gallstone-induced acute biliary pancreatitis.

Multimodal treatment with endoscopic ablation and systemic therapy for cholangiocarcinoma.

Cholangiocarcinoma (CCA) are primary malignancies of biliary system and usually unresectable at the time of diagnosis. As a consequence, majority of these cases are candidates for palliative care. With the advances in chemotherapeutic agents and multidisciplinary care, the survival rate has improved in cases with inoperable malignant biliary obstruction. As a consequence, there is a need to provide effective and durable palliative care in these patients. The main role of endoscopic palliation in the vast majority of CCA includes biliary stenting for obstructive jaundice. Recent advances in the endoscopic palliation and multimodal approach appear promising in imparting durable relief of symptoms. Use of radiofrequency ablation, photodynamic therapy and intraluminal brachytherapy has been shown to improve the survival rates as well as the patency of biliary stents. Infact, intraductal ablation may act synergistically with chemotherapy by modulating tumour signalling pathways and immune microenvironment.

To push or to pull? A clinical audit on the efficacy and safety of the pull and push percutaneous endoscopic gastrostomy techniques in oncological patients.

BACKGROUND: The peroral "pull" technique and the direct "push" procedure are the two main methods for percutaneous endoscopic gastrostomy (PEG) placement. Although pull-PEG is generally recommended as the first-line modality, many oncological patients require a push-PEG approach to prevent tumor seeding or overcome tumor-related obstruction. OBJECTIVE: We aimed to compare the efficacy and safety of both PEG procedures in cancer patients. METHODS: We retrospectively analyzed all consecutive PEG procedures within a tertiary oncological center. Patients were followed up with the hospital databases and National Cancer Registry to assess the technical success rate for PEG placement, the rate of minor and major adverse events (AEs), and 30-day mortality rates. We compared those outcomes between the two PEG techniques. Finally, risk factors for PEG-related adverse events were analyzed using a multivariable Cox proportional-hazard regression model adjusted for patients' sex, age, performance status (ECOG), Body Mass Index (BMI), diabetes, chemoradiotherapy (CRT) status (pre-/current-/post-treatment), and type of PEG. RESULTS: We included 1055 PEG procedures (58.7% push-PEG/41.4% pull-PEG) performed in 994 patients between 2014 and 2021 (mean age 62.0 [±10.7] yrs.; 70.2% males; indication: head-and-neck cancer 75.9%/other cancer 24.1%). The overall technical success for PEG placement was 96.5%. Although the "push" technique had a higher rate of all AEs (21.4% vs. 7.1%, Hazard Ratio [HR]  = 2.9; 95% CI = 1.9-4.3, p < 0.001), most of these constituted minor AEs (71.9%), such as tube dislodgement. The methods had no significant difference regarding major AEs and 30-day mortality rates. Previous CRT was associated with an increased risk of major AEs (hazard ratio = 2.7, 95% CI = 1.0-7.2, p = 0.042). CONCLUSION: The risk of major AEs was comparable between the push- and pull-PEG techniques in cancer patients. Due to frequent tube dislodgement in push-PEG, the pull technique may be more suitable for long-term feeding. Previous CRT increases the risk of major AEs, favoring early ("prophylactic") PEG placement when such treatment is expected.

Machine learning-based decision tool for selecting patients with idiopathic acute pancreatitis for endosonography to exclude a biliary aetiology.

BACKGROUND: Biliary microlithiasis/sludge is detected in approximately 30% of patients with idiopathic acute pancreatitis (IAP). As recurrent biliary pancreatitis can be prevented, the underlying aetiology of IAP should be established. AIM: To develop a machine learning (ML) based decision tool for the use of endosonography (EUS) in pancreatitis patients to detect sludge and microlithiasis. METHODS: We retrospectively used routinely recorded clinical and laboratory parameters of 218 consecutive patients with confirmed AP admitted to our tertiary care hospital between 2015 and 2020. Patients who did not receive EUS as part of the diagnostic work-up and whose pancreatitis episode could be adequately explained by other causes than biliary sludge and microlithiasis were excluded. We trained supervised ML classifiers using H2O.ai automatically selecting the best suitable predictor model to predict microlithiasis/sludge. The predictor model was further validated in two independent retrospective cohorts from two tertiary care centers (117 patients). RESULTS: Twenty-eight categorized patients' variables recorded at admission were identified to compute the predictor model with an accuracy of 0.84 [95% confidence interval (CI): 0.791-0.9185], positive predictive value of 0.84, and negative predictive value of 0.80 in the identification cohort (218 patients). In the validation cohort, the robustness of the prediction model was confirmed with an accuracy of 0.76 (95%CI: 0.673-0.8347), positive predictive value of 0.76, and negative predictive value of 0.78 (117 patients). CONCLUSION: We present a robust and validated ML-based predictor model consisting of routinely recorded parameters at admission that can predict biliary sludge and microlithiasis as the cause of AP.

Consensus definition of sludge and microlithiasis as a possible cause of pancreatitis.

OBJECTIVE: In up to 20% of patients, the aetiology of acute pancreatitis (AP) remains elusive and is thus called idiopathic. On more detailed review these cases can often be explained through biliary disease and are amenable to treatment. Findings range from biliary sludge to microlithiasis but their definitions remain fluid and controversial. DESIGN: A systematic literature review (1682 reports, following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines) analysed definitions of biliary sludge and microlithiasis, followed by an online international expert survey (30 endoscopic ultrasound/hepatobiliary and pancreatic experts; 36 items) which led to definitions of both. These were consented by Delphi voting and clinically evaluated in a retrospective cohort of patients with presumed biliary pancreatitis. RESULTS: In 13% of original articles and 19.2% of reviews, microlithiasis and biliary sludge were used synonymously. In the survey, 41.7% of experts described the term 'sludge' and 'microlithiasis' as identical findings. As a consequence, three definitions were proposed, agreed on and confirmed by voting to distinctly discriminate between biliary sludge (hyperechoic material without acoustic shadowing) and microlithiasis (echorich calculi of ≤5 mm with acoustic shadowing) as opposed to larger biliary stones, both for location in gallbladder and bile ducts. In an initial attempt to investigate the clinical relevance in a retrospective analysis in 177 confirmed cases in our hospital, there was no difference in severity of AP if caused by sludge, microlithiasis or stones. CONCLUSION: We propose a consensus definition for the localisation, ultrasound morphology and diameter of biliary sludge and microlithiasis as distinct entities. Interestingly, severity of biliary AP was not dependent on the size of concrements warranting prospective randomised studies which treatment options are adequate to prevent recurrence.

Liver phenotypes in PCOS: Analysis of exogenous and inherited risk factors for liver injury in two European cohorts.

BACKGROUND & AIMS: Fatty liver disease (FLD) is common in women with polycystic ovary syndrome (PCOS). Here, we use non-invasive tests to quantify liver injury in women with PCOS and analyse whether FLD-associated genetic variants contribute to liver phenotypes in PCOS. METHODS: Prospectively, we recruited women with PCOS and controls at two university centres in Germany and Poland. Alcohol abuse was regarded as an exclusion criterion. Genotyping of variants associated with FLD was performed using TaqMan assays. Liver stiffness measurements (LSM), controlled attenuation parameters (CAP) and non-invasive HSI, FLI, FIB-4 scores were determined to assess hepatic steatosis and fibrosis. RESULTS: A total of 42 German (age range 18-53 years) and 143 Polish (age range 18-40 years) women with PCOS, as well as 245 German and 289 Polish controls were recruited. In contrast to Polish patients, Germans were older, presented with more severe metabolic profiles and had significantly higher LSM (median 5.9 kPa vs. 3.8 kPa). In the German cohort, carriers of the PNPLA3 p.I148M risk variant had an increased LSM (p = .01). In the Polish cohort, the minor MTARC1 allele was linked with significantly lower serum aminotransferases activities, whereas the HSD17B13 polymorphism was associated with lower concentrations of 17-OH progesterone, total testosterone, and androstenedione (all p < .05). CONCLUSIONS: FLD is common in women with PCOS. Its extent is modulated by both genetic and metabolic risk factors. Genotyping of variants associated with FLD might help to stratify the risk of liver disease progression in women suffering from PCOS.

Clinical Usefulness of Non-Invasive Metabolic-Associated Fatty Liver Disease Risk Assessment Methods in Patients with Full-Blown Polycystic Ovary Syndrome in Relation to the MRI Examination with the Ideal IQ Sequence.

The coexistence of polycystic ovary syndrome (PCOS) and liver steatosis has been studied for years. The gold standards for the diagnosis of liver steatosis are liver biopsy and magnetic resonance imaging (MRI), which are invasive and expensive methods. The main aim of this study is to check the usefulness of lipid accumulation product (LAP) and free androgen index (FAI) in the diagnosis of liver steatosis. The Ideal IQ MRI was performed in 49 women with PCOS phenotype A to assess the degree of liver steatosis, which was expressed with the proton density fat fraction (PDFF). Anthropometric examination and laboratory tests were performed, and the LAP and FAI were calculated. The correlation between MRI results and LAP, FAI, and one of the FAI components, sex hormone binding globulin (SHBG), was checked using statistical tests. There is a statistically significant correlation between PDFF and LAP and also between PDFF and FAI. LAP = 70.25 and FAI = 5.05 were established as cut-offs to diagnose liver steatosis. The SHBG is not a statistically significant parameter to predict liver steatosis. The study showed that especially LAP, but also FAI, can be used to predict liver steatosis with high specificity and sensitivity.

Impact of tumor size and location on endoscopic ultrasound-guided sampling of pancreatic neuroendocrine tumors: A recursive partitioning analysis.

BACKGROUND: Current guidelines provide weak recommendations to treat small (<2 cm) non-functional pancreatic neuroendocrine tumors with low Ki-67 proliferation index either by resection or clinical follow-up. However, there is a lack of consensus regarding the minimal size of pNET, which allows EUS-guided biopsy with high enough diagnostic accuracy for stratification. METHODS: We conducted a retrospective, bicentric analysis of patients who had undergone EUS-guided pNET sampling in two tertiary care Endoscopy Units in Germany and Poland. Using a recursive partitioning of the tree-aided model, we aimed to stratify the probability of successful EUS-guided biopsy of pNET lesions according to their size and location. RESULTS: In our pNET cohort, successful histological confirmation of a pNET diagnosis was achieved in 59/69 (85.5%) cases at the initial EUS-guided biopsy. In 41 patients with a pNET size less than 18.5 mm, the EUS-guided first biopsy was successful in 90.2%. In 16 of these patients with smaller lesions, EUS-guided sampling was 100% in very small (less than 11 mm) and extremely small lesions (less than 8 mm). The biopsy success rate was 100% in tail lesions in the size range between ≥5.95 and <8.1 mm but only 33.3% independent of the investigator in pancreatic head or body, with an error rate of 11.2% CONCLUSION: Using a recursive partitioning of the tree-aided stratification model, we demonstrate for the first time that in balancing risks and benefits, very small pNETs (<1 cm) in the tail of the pancreas should be sampled under EUS-guidance.

Practical approach to linear EUS examination of the mediastinum.

EUS has become a substantial diagnostic and therapeutic modality for many anatomical regions. The extent of endosonographic assessment is wide, and among others, allows for the evaluation of the mediastinal anatomy and related pathologies such as mediastinal lymphadenopathy and staging of central malignant lung lesions. Moreover, EUS assessment has proved more accurate in detecting small lesions missed by standard imaging examinations such as computed tomography or magnetic resonance. Endosonographically, various mediastinal anatomical landmarks and stations can be visualized by transesophageal scanning, thus providing arranged systematic examination of the mediastinum. In addition, the correct position during the examination is crucial for EUS-guided procedures such as tissue sampling and drainage of mediastinal abscesses. The evolution of EUS-guided diagnostic and interventional procedures has contributed to the increasing importance of understanding the mediastinal anatomy during the EUS examination.

COVID-19 and Canadian Gastroenterology Trainees.

BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic has impacted endoscopy services and education worldwide. This study aimed to characterize the impact of COVID-19 on gastroenterology trainees in Canada. METHODS: An analysis of Canadian respondents from the international EndoTrain survey, open from April 11 to May 2 2020 and distributed by program directors, trainees, and national and international gastroenterology societies' representatives, was completed. The survey included questions on monthly endoscopy volume, personal protective equipment availability, trainee well-being and educational resources. The primary outcome was change in procedural volume during the COVID-19 pandemic. Secondary outcomes included trainee's professional and personal concerns, anxiety and burnout. RESULTS: Thirty-four Canadian trainees completed the survey. Per month, participants completed a median of 30 esophagogastroduodenoscopies (interquartile range 16 to 50) prior to the pandemic compared to 2 (0 to 10) during the pandemic, 20 (8 to 30) compared to 2 (0 to 5) colonoscopies and 3 (1 to 10) compared to 0 (0 to 3) upper gastrointestinal bleeding procedures. There was a significant decrease in procedural volumes between the pre-COVID-19 and COVID-19 time periods for all procedures (P < 0.001). Thirty (88%) trainees were concerned about personal COVID-19 exposure, 32 (94%) were concerned about achieving and/or maintaining clinical competence and 24 (71%) were concerned about prolongation of training time due to the pandemic. Twenty-six (79%) respondents experienced some degree of anxiety, and 10 (31%) experienced some degree of burnout. CONCLUSION: The COVID-19 pandemic has substantially impacted gastroenterology trainees in Canada. As the pandemic eases, it important for gastrointestinal programs to adapt to maximize resident learning, maintain effective clinical care and ensure development of endoscopic competence.

Incidental Finding of a PSMA-Positive Pancreatic Cancer in a Patient Suffering from a Metastasized PSMA-Positive Prostate Cancer.

An 82-year-old man suffering from prostate cancer that was scheduled for a radioreceptor-ligand therapy (RLT) presented with jaundice to our service. An abdominal ultrasound (US) revealed obstructive extrahepatic cholestasis due to a solid lesion located in the uncinate process of the pancreas. The Prostate Specific Membrane Antigen (PSMA) PET/CT prior to RLT showed multilocular PSMA positive tumor lesions in the lymph nodes, the lung and the pancreas. On request of the cancer board, an Endoscopic Ultrasound (EUS)-guided Fine-Needle Aspiration (FNA) of the pancreatic mass was performed revealing invasive pancreatic ductal adenocarcinoma incompatible with a prostate cancer metastasis leading to the diagnosis of a PSMA positive pancreatic ductal adenocarcinoma.

Influence of COVID-19 Pandemic on Endoscopic Procedures in Two European Large-Capacity Endoscopy Units: "Keep Calm, Keep Safe and Scope on?"

BACKGROUND: The COVID-19-pandemic poses challenges to the medical system and especially to endoscopic staff and patients. National, European and International societies provided recommendations on how to safely perform endoscopic procedures during the current pandemic. Until now, the effect of the current pandemic on tertiary endoscopy centers has not been reported. OBJECTIVE: The aim of this was to analyze the influence of the early SARS-CoV2-pandemic on endoscopic care and work flow in 2 European tertiary endoscopy units. METHODS: Data from 2 tertiary endoscopy units (Katowice and Munich) were retrospectively collected during the early pandemic and compared to an equivalent pre-pandemic period. Data include procedures, complications, benchmarks, and influence on endoscopy training. RESULTS: During the early pandemic, we noted a highly significant decrease (49.1%) in the overall number of all endoscopies with a significant increase in therapeutic procedures. Besides, there were no significant differences in the number of urgent endoscopic retrograde cholangiopancreatography or interventional endoscopic ultrasound procedures. The exceptional situation reduced endoscopic procedures performed by trainees significantly. CONCLUSIONS: The SARS-CoV2-pandemic halved the endoscopy service of 2 tertiary centers while maintaining an urgent therapeutic service. Recommended personal safety measures in endoscopy proved to be efficient and safe in preventing SARS-CoV2 infection of staff or spreading. Unnecessarily, the SARS-CoV2 pandemic prevented routine endoscopy training.

What Do We Currently Know about the Pathophysiology of Alcoholic Pancreatitis: A Brief Review.

BACKGROUND: Alcoholic pancreatitis is a serious medical concern worldwide and remains to be one of the common causes of pancreatic disease. SUMMARY: While alcohol consumption causes direct damage to pancreatic tissue, only a small percentage of active drinkers will develop pancreatitis. An explanation of this phenomenon is probably that alcohol increases pancreatic vulnerability to damage; however, the simultaneous presence of additional risk factors and pancreatic costressors is required to increase the risk of pancreatitis and its complications caused by alcohol misuse. Recently, a number of important genetic as well as environmental factors influencing the risk of alcoholic pancreatitis have been described. KEY MESSAGES: In brief, this review reports established factors for the development of alcoholic pancreatitis and summarizes recent progress made in basic and clinical research.

Impact of COVID-19 on endoscopy trainees: an international survey.

BACKGROUND AND AIMS: Although coronavirus disease 2019 (COVID-19) has affected endoscopy services globally, the impact on trainees has not been evaluated. We aimed to assess the impact of COVID-19 on procedural volumes and on the emotional well-being of endoscopy trainees worldwide. METHODS: An international survey was disseminated over a 3-week period in April 2020. The primary outcome was the percentage reduction in monthly procedure volume before and during COVID-19. Secondary outcomes included potential variation of COVID-19 impact between different continents and rates and predictors of anxiety and burnout among trainees. RESULTS: Across 770 trainees from 63 countries, 93.8% reported a reduction in endoscopy case volume. The median percentage reduction in total procedures was 99% (interquartile range, 85%-100%), which varied internationally (P < .001) and was greatest for colonoscopy procedures. Restrictions in case volume and trainee activity were common barriers. A total of 71.9% were concerned that the COVID-19 pandemic could prolonged training. Anxiety was reported in 52.4% of respondents and burnout in 18.8%. Anxiety was independently associated with female gender (odds ratio [OR], 2.15; P < .001), adequacy of personal protective equipment (OR, 1.75; P = .005), lack of institutional support for emotional health (OR, 1.67; P = .008), and concerns regarding prolongation of training (OR, 1.60; P = .013). Modifying existing national guidelines to support adequate endoscopy training during the pandemic was supported by 68.9%. CONCLUSIONS: The COVID-19 pandemic has led to restrictions in endoscopic volumes and endoscopy training, with high rates of anxiety and burnout among endoscopy trainees worldwide. Targeted measures by training programs to address these key issues are warranted to improve trainee well-being and support trainee education.

Risk Stratification and Early Conservative Treatment of Acute Pancreatitis.

BACKGROUND: Acute pancreatitis (AP) is a potentially life-threatening common gastrointestinal disorder with increasing incidence around the globe. Although the majority of cases will take an uneventful, mild course, a fraction of patients is at risk of moderately severe or severe pancreatitis which is burdened with substantial morbidity and mortality. Early identification of patients at risk of a severe disease course and an adopted treatment strategy are crucial to avoid adverse outcomes. SUMMARY: In this review we summarize the most recent concepts of severity grading in patients diagnosed with AP by adopting recommendations of current guidelines and discussing them in the context of the available literature. The severity of AP depends on the presence of local and/or systemic complications and organ failure. To predict the severity early in the disease course, host-specific factors (age, comorbidities, body mass index), clinical risk factors (biochemical and physiological parameters and scoring systems), as well as the response to initial therapy need to be considered and revisited in the short term. Depending on the individual risk and comorbidity the initial treatment can be guided, which will be discussed in the second part of this review. KEY MESSAGE: Predicting the severity of AP and adapting the individual treatment strategy requires multidimensional risk assessment and close observation during the early phase of AP development.