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.

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.

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.

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.

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.

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.

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.

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.

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.

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).