Development of a novel CT-based index for predicting the number of extracorporeal shockwave lithotripsy (ESWL) sessions required for successful fragmentation of obstructing pancreatic duct stones.

BACKGROUND & AIM: Extracorporeal shock wave lithotripsy (ESWL) is used for the treatment of pancreatic duct stones (PDS) in patients with chronic pancreatitis (CP). We aimed to develop a CT based index to predict the required number of ESWL sessions for technical success. METHODS: We retrospectively evaluated patients with PDS secondary to CP who underwent ESWL. Technical success was defined as the complete fragmentation of stones to <3 mm. CT features including PDS size, number, location, and density in Hounsfield units (HU) were noted. We analyzed the relationship between PDS characteristics and the number of ESWL sessions required for technical success. A multiple linear regression model was used to combine size and density into the pancreatic duct stone (PDS) index that was translated into a web-based calculator. RESULTS: There were 206 subjects (mean age 38.6 ± 13.7 years, 59.2% male) who underwent ESWL. PDS size showed a moderate correlation with the number of ESWL sessions (r = 0.42, p < 0.01). PDS in the head required a fewer number of sessions in comparison to those in the body (1.4 ± 0.6 vs. 1.6 ± 0.7, p = 0.01). There was a strong correlation between PDS density and the number of ESWL sessions (r = 0.617, p-value <0.01). The PDS index {0.3793 + [0.0009755 x PDS density (HU)] + [0.02549 x PDS size (mm)]} could accurately predict the required number of ESWL sessions with an AUC of 0.872 (p < 0.01). CONCLUSION: The PDS index is a useful predictor of the number of ESWL sessions needed for technical success that can help in planning and patient counseling.

Current and Emerging Applications of Artificial Intelligence (AI) in the Management of Pancreatobiliary (PB) disorders.

PURPOSE OF REVIEW: In this review, we aim to summarize the existing literature and future directions on the use of artificial intelligence (AI) for the diagnosis and treatment of PB (pancreaticobiliary) disorders. RECENT FINDINGS: AI models have been developed to aid in the diagnosis and management of PB disorders such as pancreatic adenocarcinoma (PDAC), pancreatic neuroendocrine tumors (pNETs), acute pancreatitis, chronic pancreatitis, autoimmune pancreatitis, choledocholithiasis, indeterminate biliary strictures, cholangiocarcinoma and endoscopic procedures such as ERCP, EUS, and cholangioscopy. Recent studies have integrated radiological, endoscopic and pathological data to develop models to aid in better detection and prognostication of these disorders. AI is an indispensable proponent in the future practice of medicine. It has been extensively studied and approved for use in the detection of colonic polyps. AI models based on clinical, laboratory, and radiomics have been developed to aid in the diagnosis and management of various PB disorders and its application is ever expanding. Despite promising results, these AI-based models need further external validation to be clinically applicable.

Interpretation of serum pancreatic enzymes in pancreatic and nonpancreatic conditions.

PURPOSE OF REVIEW: Serum levels of amylase and lipase can be elevated in nonpancreatic conditions that may or may not be associated with abdominal pain. This leads to a large proportion of patients being falsely labeled as having acute pancreatitis. In this review, we aim to summarize the existing evidence on pancreatic enzyme elevation in various pancreatic and nonpancreatic conditions and its practical implications in clinical practice and healthcare. RECENT FINDINGS: Serum amylase and lipase levels are not specific for pancreatitis. Attempts have been made to validate newer biomarkers including pancreatic elastase, serum trypsin, urinary trypsinogen-activated peptide, phospholipase A2, carboxypeptidase B, activated peptide of carboxypeptidase B, the trypsin 2 alpha 1 activation complex, and circulating cell-free DNA for the diagnosis of acute pancreatitis. SUMMARY: Serum lipase levels can be elevated in many intra-abdominal inflammatory conditions. Although more sensitive and specific than amylase, serum lipase levels are not sufficient to diagnose acute pancreatitis in patients with abdominal pain. There is a need to increase stress on radiological evidence as well increase cut-off levels of enzyme elevation for a more accurate diagnosis of acute pancreatitis.

Pancreatic duct pressure: A review of technical aspects and clinical significance.

Pancreatic duct pressure (PDP) dynamics comprise an intricately modulated system that helps maintain homeostasis of pancreatic function. It is affected by various factors, including the rate of pancreatic fluid secretion, patency of the ductal system, sphincter of Oddi function, and pancreatic fluid characteristics. Disease states such as acute and chronic pancreatitis can alter the normal PDP dynamics. Ductal hypertension or increased PDP is suspected to be involved in the pathogenesis of pancreatic pain, endocrine and exocrine pancreatic insufficiency, and recurrent pancreatitis. This review provides a comprehensive appraisal of the available literature on PDP, including the methods used in the measurement and clinical implications of elevated PDP.

Rectal INdomethacin, oral TacROlimus, or their combination for the prevention of post-ERCP pancreatitis (INTRO Trial): Protocol for a randomized, controlled, double-blinded trial.

BACKGROUND: Acute pancreatitis remains the most common and morbid complication of endoscopic retrograde cholangiopancreatography (ERCP). The use of rectal indomethacin and pancreatic duct stenting has been shown to reduce the incidence and severity of post-ERCP pancreatitis (PEP), but these interventions have limitations. Recent clinical and translational evidence suggests a role for calcineurin inhibitors in the prevention of pancreatitis, with multiple retrospective case series showing a reduction in PEP rates in tacrolimus users. METHODS: The INTRO trial is a multicenter, international, randomized, double-blinded, controlled trial. A total of 4,874 patients undergoing ERCP will be randomized to receive either oral tacrolimus (5 mg) or oral placebo 1-2 h before ERCP, and followed for 30 days post-procedure. Blood and pancreatic aspirate samples will also be collected in a subset of patients to quantify tacrolimus levels. The primary outcome of the study is the incidence of PEP. Secondary endpoints include the severity of PEP, ERCP-related complications, adverse drug events, length of hospital stay, cost-effectiveness, and the pharmacokinetics, pharmacodynamics, and pharmacogenomics of tacrolimus immune modulation in the pancreas. CONCLUSIONS: The INTRO trial will assess the role of calcineurin inhibitors in PEP prophylaxis and develop a foundation for the clinical optimization of this therapeutic strategy from a pharmacologic and economic standpoint. With this clinical trial, we hope to demonstrate a novel approach to PEP prophylaxis using a widely available and well-characterized class of drugs. TRIAL REGISTRATION: NCT05252754, registered on February 14, 2022.

Ascites in Acute Pancreatitis: Clinical Implications and Management.

Clinically significant ascites in acute pancreatitis (AP) is rarely encountered and is a result of multifactorial pathogenesis. Early reactionary ascites in AP usually does not require any treatment and resolves spontaneously in majority of patients. A diagnostic analysis should be performed in case of ascites developing in the latter stages with increasing pain or worsening organ failure. Low serum albumin-ascites gradient ascites with amylase > 1000 U/l is highly suggestive of pancreatic ascites that is usually associated with duct disruption. A combination of nasojejunal feeding, subcutaneous octreotide, endoscopic drainage and rarely, surgery are employed in managing this difficult to treat condition. There is a need of further studies to better understand the clinical role of ascites as well as contribution of other factors like hypoalbuminemia and portal hypertension to its development in AP.

Perforations from Endoscopic Dilation of Corrosive Strictures in Adults: A Systematic Review and Meta-Analysis.

BACKGROUND AND AIMS: Endoscopic dilation is an important therapeutic option for treatment of corrosive strictures. Its safety is unclear with variable perforation rates in previous studies. We aimed to evaluate its safety with regard to perforations and the effect of dilator type to perforation risk. METHODS: A systematic review of published literature from inception to April 24, 2021, using PubMed and EMBASE databases was conducted. Studies in adult subjects (mean age ≥ 18 years) reporting perforation rates of endoscopic dilation of corrosive esophageal and/or gastric strictures were included. Pooled cumulative perforation rates were computed as primary outcome. Secondary outcomes included, perforation with each dilator subtypes, surgical or conservative modes of management and mortality. Random effect meta-analysis was used to estimate the frequency of each of these outcomes. Variables were reported as percentages with 95% CI. RESULTS: A total of 712 subjects (N) who underwent 4840 dilations (n) were noted in the 15 studies that were included. Of which, eight were retrospective, while the remaining seven were prospective. On meta-analysis, the cumulative pooled perforation rate was 1% (1-2%) of the number of dilations (n%). The perforation rates with SG (1%, 0-3%) and balloon (1%, 0-5%) dilators were similar (p value < 0.01). 45/64 (59%, 11-94%) perforations were subjected to surgery while the remaining 14/64 (41%, 6-89%) was managed conservatively. Choice of management strategy was biased to the norms of the treating team. About 3/712 patients (0%, 0-2%) succumbed following perforation. CONCLUSION: Perforation from endoscopic dilation of corrosive strictures occurs rarely, and there is no significant difference in perforation risk related to the type of dilator.

Sham Feeding Induced Gastric Acid Secretion in Patients with Caustic Induced Esophageal Stricture.

Caustic ingestion can lead to structural changes in the upper gastro-intestinal tract. However, there is limited data on the effect of caustic ingestion on gastric secretion. This study was planned to determine changes in gastric acid output after sham feeding in patients with caustic induced esophageal stricture and to compare it with healthy controls. It was a prospective study done at tertiary care center in North India. Consecutive patients with caustic induced esophageal stricture were evaluated for the study. Gastric secretory function was estimated in the basal state and after modified sham feeding. These results were compared with age-matched controls. The mean age of the included patients (n = 18) was 30.11 ± 9.19 years and 13 patients were male. 16 (88%) patients had history of acid ingestion. Patients with caustic sequelae had significantly lower basal and stimulated acid secretion compared to controls (n = 10) (5.84 ± 2.44 mmol/hr; p < 0.01 and 17.16 ± 7.53 mmol/hr; p < 0.01; respectively). Patients with lower esophageal stricture (n = 8) had significantly lower increase in acid output compared to patients with stricture elsewhere in esophagus (0.20 ± 0.3 vs. 2.31 ± 1.74 mmol/hr, p < 0.01). Patients with lower esophageal involvement had significantly lower stimulated acid secretion and increase in acid secretion compared to controls (4.74 ± 4.67 vs. 17.16 ± 7.53 mmol/hr; p < 0.01 and 20 ± 0.3 vs. 2.09 ± 0.88 mmol/hr; p < 0.01; respectively).

Renal doppler changes in patients with acute pancreatitis: A prospective study.

BACKGROUND: Renal Doppler to assess renal resistive index (RRI) is an attractive option to prognosticate acute kidney injury (AKI) in acute pancreatitis (AP) as it is feasible within scope of point-of-care ultrasound. However, RRI has been infrequently evaluated in AP. OBJECTIVE: Prospectively study diagnostic and prognostic performance of RRI in patients with AP. METHODOLOGY: 75 patients with AP were prospectively enrolled and followed till recovery/death. All patients were subjected to renal Doppler and RRI was compared between patients with and without AKI. RESULTS: Thirty six patients developed AKI and 39 patients did not develop AKI. AKI network stage 1, 2 and 3 AKI was seen in 7(19.4%), 12(33.3%) and 17 (47.2%) patients respectively. Prognostic scoring done at admission by SIRS, modified marshal score, and BISAP scores, as well as duration of hospitalization and mortality rates were significantly higher in patients with AKI. Mean peak systolic velocity and RRI at upper, middle and lower poles of bilateral kidneys were comparable between patients with and without AKI. The RRI was abnormal in 46 (66.6%) patients and it was <0.6 in 35/46 (76%) and >0.7 in 11/46 (24%) patients respectively. RRI <0.6 was observed in 16 (53.3%) and 19 (48.7%) patients with and without AKI respectively (p = 0.80). RRI >0.7 was observed in 4 (53.3%) and 7 (48.7%) patients with and without AKI respectively (p = 0.74). CONCLUSIONS: AKI is associated with poor prognosis in AP. RRI on renal Doppler at admission seems to have poor diagnostic as well as prognostic performance for AKI in patients with AP.

Predicting the severity of acute pancreatitis: Current approaches and future directions.

Acute pancreatitis (AP) is a sudden-onset inflammatory disease of the pancreas. The severity of AP is classified into mild, moderate, and severe categories based on the presence and persistence of organ failure. Severe acute pancreatitis (SAP) can be associated with significant morbidity and mortality. It requires early recognition for appropriate timely management. Prognostic scores for predicting SAP incorporating many clinical, laboratory, and radiological parameters have been developed in the past. However, all of these prognostic scores have low positive predictive value for SAP and some of these scores require >24 h for assessment. There is a need to develop biomarkers that can accurately identify patients at risk for SAP early in the course of the presentation. In this review, we aim to provide a summary of the most commonly utilized prognostic scores for AP and discuss future directions.

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.

A New Entity of Walled off Extra Pancreatic Necrosis is Associated with Better Outcomes Following Endoscopic Transmural Drainage.

BACKGROUND AND AIMS: Previous studies have shown that patients with extra-pancreatic necrosis (EPN) alone are associated with better outcomes than patients with pancreatic necrosis (PN) in acute pancreatitis (AP). The natural history and drainage outcome of pancreatic collections resulting from PN vs. EPN has not been studied. METHODS: Clinical records of a prospectively maintained cohort of AP patients who underwent endoscopic drainage of walled of necrosis (WON) were reviewed. Computed tomography (CT) done on day 4 to 7 of illness was reviewed to identify EPN alone (Group 1) or PN with or without EPN (Group 2). Group 1 and 2 were compared for WON characteristics, as well as outcome and adverse effects of endoscopic drainage. RESULTS: Seventy-one patients in Group 2 (57 males; mean age 38.6±11.5 years) were compared with sixteen patients in Group 1 (12 males; mean age 34.5±10.8 years). WON developing in Group 2 were significantly larger (11.7±2.8 cm vs. 9.5±2.03 cm) with higher solid necrotic debris (30.4±9.8% vs. 13.7±7.2%). Endoscopic transmural drainage of WON associated with PN required a greater number of direct endoscopic necrosectomy (DEN) sessions along with a longer time for resolution. The time taken for resolution correlated with size (r=0.629, p <0.01) and solid debris content (r=0.647, p<0.01), which were significantly higher in the PN group. CONCLUSIONS: This new entity of walled of extra pancreatic necrosis alone has lesser solid necrotic debris and its endoscopic drainage is associated with better outcomes as compared to patients with walled off pancreatic necrosis.

Lower cyst fluid carcinoembryonic antigen cutoff is helpful in the differential diagnosis of mucinous versus non-mucinous pancreatic cysts.

BACKGROUND AND AIM: Pancreatic cystic lesions (PCLs) are being diagnosed with increased frequency and have varying neoplastic potential. We conducted this multimodal, prospective study to evaluate  the role of tumor cytology and molecular markers to differentiate PCL subtypes. METHODS: Consecutive undiagnosed patients with PCLs (n = 100, mean age: 50.37 years; 41% males) were prospectively studied. Cyst fluid carcinoembryonic antigen (CEA), CA19.9, CA125, CA72.4, and vascular endothelial growth factor-alpha (VEGF-α) levels were measured by quantitative enzyme-linked immunosorbent assay (ELISA) method. Mutational analysis of the KRAS gene (exon 2, Codon 12 and 13) and GNAS gene (Exon 8, Codon 201) were performed by Sanger's sequencing. RESULTS: The mean cyst size was 4.32 ± 2.4 cm. Fluid cytology revealed definitive diagnosis in 21 (22.3%) patients. All malignant PCLs could be identified on cytology whereas 10/14 (71%) non-malignant mucinous PCLs could also be identified on cytology based on mucin staining. Among the tested tumor markers, cyst fluid CEA had the best diagnostic performance for differentiation between mucinous and non-mucinous PCLs (AUC 0.933 [95% CI 0.86-0.91]). At a cyst fluid CEA cutoff level of 45.0 ng/mL, the sensitivity, specificity, positive predictive value, and negative predictive value for differentiation between mucinous and non-mucinous cysts were 88.5%, 96.8%, 92.0%, and 95.3%, respectively (p < 0.05). KRAS and GNAS mutation had no significant diagnostic benefit in comparison to fluid cytology and CEA levels. CONCLUSIONS: Fluid CEA at a lower cutoff of 45 ng/mL is the most accurate marker to differentiate between mucinous and non-mucinous PCL. The KRAS and GNAS mutational analysis does not improve upon the diagnostic performance of fluid cytology and tumor markers.

Comparison of demographic profile, risk factors, and in-hospital outcome in young and old patients with acute coronary syndrome: A single-center experience.

BACKGROUND: Coronary artery disease (CAD) is witnessing a demographic transition with increasing prevalence in younger individuals. Data is scarce comparing various characteristics of acute coronary syndrome (ACS) between young and old patients in an Indian setting. Hence, we evaluated the epidemiological, demographic, risk factor, and outcome profile of young and old ACS patients in Indian setting. METHODS: This was a prospective observational study, which enrolled 50 consecutive ACS patients each into two groups: younger (≤45 years) and elderly (>45 years), respectively. Comparison of clinical presentation, electrocardiography, echocardiographic findings, conventional, nonconventional risk factors, and in-hospital outcomes including duration of hospital stay and major adverse cardiac events (MACE) were made between the two groups. Multivariate regression analysis of risk factors as determinants of MACE adjusting for other confounding factors was also performed. RESULTS: Fifty patients in each group were compared. Mean age in the younger and elderly group was 36 ± 4.69 and 61.58 ± 10.69 years, respectively. Male sex, smoking, family history of CAD, hyperhomocysteinemia, and obesity were observed more in the younger population. While dyslipidemia, low physical activity, diabetes mellitus, and history of previous ACS was more in the older population. Single-vessel disease was more common in younger patients while multivessel involvement was more common in elderly patients. Older patients had longer hospital stays and more in-hospital MACE including deaths. By multivariate analysis, shock was found to be an independent predictor of MACE in both groups. CONCLUSION: Younger ACS patients have a different risk profile and better in-hospital outcomes compared to older patients.