Early identification of malignant biliary strictures (MBSs) is challenging, with up to 20% classified as indeterminants after preliminary testing and tissue sampling with endoscopic retrograde cholangiopancreatography. We aimed to evaluate the use of methylated DNA markers (MDMs) from biliary brushings to enhance MBS detection in a prospective cohort.

Candidate MDMs were evaluated for their utility in MBS diagnosis through a series of discovery and validation phases. DNA was extracted from biliary brushing samples, quantified, bisulfite-converted, and then subjected to methylation-specific droplet digital polymerase chain reaction.  Patients were considered to have no malignancy if the sampling was negative and there was no evidence of malignancy after 1 year or definitive negative surgical histopathology.

Fourteen candidate MDMs were evaluated in the discovery phase, with top-performing and new markers evaluated in the technical validation phase. The top 4 MDMs were TWIST1, HOXA1, VSTM2B, and CLEC11A, which individually achieved AUC values of 0.82, 0.81, 0.83, and 0.78, respectively, with sensitivities of 59.4%, 53.1%, 62.5%, and 50.0%, respectively, at high specificities for malignancy of 95.2%-95.3% for the final biologic validation phase. When combined as a panel, the AUC was 0.86, achieving 73.4% sensitivity and 92.9% specificity, which outperformed cytology and fluorescence in situ hybridization (FISH).

The selected MDMs demonstrated improved performance characteristics for the detection of MBS compared to cytology and FISH. Therefore, MDMs should be considered viable candidates for inclusion in diagnostic testing algorithms.

Idiopathic acute pancreatitis (IAP) presents a diagnostic challenge and refers to cases where the cause of acute pancreatitis remains uncertain despite a comprehensive diagnostic evaluation. Endoscopic ultrasound (EUS) has emerged as a valuable tool in the diagnostic workup of IAP. This review explores the pivotal role of EUS in detecting the actual cause of IAP and assessing its accuracy, timing, safety, and future technological improvement. In this review, we investigate the role of EUS in identifying the actual cause of IAP by examining the available literature. We aim to assess possible existing evidence regarding EUS accuracy, timing, and safety and explore potential trends of future technological improvements in EUS for diagnostic purposes. Following PRISMA guidelines, 60 pertinent studies were selected and analysed. EUS emerges as a crucial diagnostic tool, particularly when conventional imaging fails. It can offer intricate visualization of the pancreas, biliary system, and adjacent structures. Microlithiasis, biliary sludge, chronic pancreatitis, and small pancreatic tumors seem to be much more accurately identified with EUS in the setting of IAP. The optimal timing for EUS is post-resolution of the acute phase of the disease. With a low rate of complications, EUS poses minimal safety concerns. EUS-guided interventions, including fine-needle aspiration, collection drainage, and biopsies, aid in the cytological analysis. With high diagnostic accuracy, safety, and therapeutic potential, EUS is able to improve patient outcomes when managing IAP. Further refinement of EUS techniques and cost-effectiveness assessment of EUS-guided approaches need to be explored in multicentre prospective studies. This review underscores EUS as a transformative tool in unraveling IAP's enigma and advancing diagnostic and therapeutic strategies.

Pancreatic divisum (PD) is a malformation wherein the majority of affected patients remain asymptomatic or present with complications early in life. Some cases, however, may present in adulthood with recurrent pancreatitis, which makes the diagnosis clinically challenging. Here, we present a rare case of an elderly female with acute-on-chronic epigastric pain secondary to pancreatitis due to PD. During hospitalization, the patient was treated for acute pancreatitis and subsequently discharged with recommendations for corrective surgery. This case is unique particularly due to the older age of onset of symptoms, as well as the lack of exacerbating factors such as drug abuse, alcohol, or obesity. This case highlights the importance of considering PD as a differential diagnosis when managing patients with recurrent pancreatitis regardless of their age.

Pancreatic duct stenting using endoscopy or surgery is widely used for the management of benign and malignant pancreatic diseases. Endoscopic pancreatic stents are mainly used to relieve pain caused by chronic pancreatitis and pancreas divisum, and to treat pancreatic duct disruption and stenotic pancreaticointestinal anastomosis after surgery. They are also used to prevent postendoscopic retrograde cholangiopancreatography pancreatitis and postoperative pancreatic fistula, treat pancreatic cancer, and locate radiolucent stones. Recent advances in endoscopic techniques, such as endoscopic ultrasonography and balloon enteroscopy, and newly designed stents have broadened the indications for pancreatic duct stenting. In this review we outlined the types, insertion procedures, efficacy, and complications of endoscopic pancreatic duct stent placement, and summarized the applications of pancreatic duct stents in surgery.

There are limited data about the benign biliary strictures (BBS) which can develop during the clinical course of acute biliary pancreatitis (ABP) due to compression of the common bile duct (CBD) by edematous and inflamed pancreatic tissue. We aimed to determine the incidence of BBS due to ABP and its clinical course after endoscopic management.

The study was retrospectively conducted among patients with ABP who were admitted to a single tertiary reference center during 3 years. BBS-ABP was defined as distal narrowing of the CBD with proximal dilatation and delayed drainage of the contrast into the duodenum. Endoscopic treatment was performed by inserting a single 7F or 10F plastic stent which was exchanged every 3 months until stricture resolution. Patients were followed for 1 year after stricture resolution.

Seven hundred and twenty-one patients had ABP during the study period. Among them, 257 (35.6%) patients underwent ERCP and 26 patients (3.6%) had CBD stricture due to ABP. A 7 Fr plastic stent was inserted in 18 patients and 10 Fr in 8 patients. The stricture was completely resolved at 3 months in 66.7%, at 6 months 23.8% and at 9 months (9.5%) of the patients. There was no procedure-related complications other than asymptomatic stent migration in 4 (19%) patients. None of the patients had recurrent biliary stricture during the 1 year stent-free follow-up period.

BBS-ABP is a frequently seen clinical entity. In most patients, the stricture improves within 3 months and temporary endoscopic stenting prevents the patients from the consequences of the obstruction during this period.

Endoscopic ultrasound (EUS)-guided main pancreatic duct (PD) access may be used when conventional endoscopic retrograde cholangiopancreatography (ERCP) techniques fail. The use of a percutaneous transluminal angioplasty balloon (PTAB), originally developed for vascular interventions, can be used to facilitate transmural (e.g., transgastric) PD access and to dilate high-grade pancreatic strictures.

To describe the technique, efficacy, and safety of PTABs for EUS-guided PD interventions.

Patients who underwent EUS with use of a PTAB from March 2011 to August 2021 were retrospectively identified from a tertiary care medical center supply database. PTABs included 3-4 French angioplasty catheters with 3-4 mm balloons designed to use over a 0.018-inch guidewire. The primary outcome was technical success. Secondary outcomes included incidence of adverse events (AEs) and need for early reintervention.

A total of 23 patients were identified (48% female, mean age 55.8 years). Chronic pancreatitis was the underlying etiology in 13 (56.5%) patients, surgically altered anatomy (SAA) with stricture in 7 (30.4%), and SAA with post-operative leak in 3 (13.0%). Technical success was achieved in 20 (87%) cases. Overall AE rate was 26% (n = 6). All AEs were mild and included 1 pancreatic duct leak, 2 cases of post-procedure pancreatitis, and 3 admissions for post-procedural pain. No patients required early re-intervention.

EUS-guided use of PTABs for PD access and/or stricture management is feasible with an acceptable safety profile and can be considered in patients when conventional ERCP cannulation fails.

We described two cases of acute pancreatitis secondary to ansa pancreatica. The first patient was diagnosed on MRCP and improved after standard treatment of AP. In the second case, ansa pancreatica was diagnosed on IOP. At the second episode of AP, sphincterotomy of the minor papilla was performed.

Aberrant expression of miRNAs in pancreatic islets is closely related to the development of type 1 diabetes (T1D). The aim of this study was to identify key miRNAs dysregulated in pancreatic islets during T1D progression and to develop a theranostic approach to modify their expression using an MRI-based nanodrug consisting of iron oxide nanoparticles conjugated to miRNA-targeting oligonucleotides in a mouse model of T1D. Isolated pancreatic islets were derived from NOD mice of three distinct age groups (3, 8 and 18-week-old). Total RNA collected from cultured islets was purified and global miRNA profiling was performed with 3D-Gene global miRNA microarray mouse chips encompassing all mouse miRNAs available on the Sanger miRBase V16. Of the miRNAs that were found to be differentially expressed across three age groups, we identified one candidate (miR-216a) implicated in beta cell proliferation for subsequent validation by RT-PCR. Alterations in miR-216a expression within pancreatic beta cells were also examined using in situ hybridization on the frozen pancreatic sections. For in vitro studies, miR-216a mimics/inhibitors were conjugated to iron oxide nanoparticles and incubated with beta cell line, βTC-6. Cell proliferation marker Ki67 was evaluated. Expression of the phosphatase and tensin homolog (PTEN), which is one of the direct targets of miR-216a, was analyzed using western blot. For in vivo study, the miR-216a mimics/inhibitors conjugated to the nanoparticles were injected into 12-week-old female diabetic Balb/c mice via pancreatic duct. The delivery of the nanodrug was monitored by in vivo MRI. Blood glucose of the treated mice was monitored post injection. Ex vivo histological analysis of the pancreatic sections included staining for insulin, PTEN and Ki67. miRNA microarray demonstrated that the expression of miR-216a in the islets from NOD mice significantly changed during T1D progression. In vitro studies showed that treatment with a miR-216a inhibitor nanodrug suppressed proliferation of beta cells and increased the expression of PTEN, a miR-216a target. In contrast, introduction of a mimic nanodrug decreased PTEN expression and increased beta cell proliferation. Animals treated in vivo with a mimic nanodrug had higher insulin-producing functionality compared to controls. These observations were in line with downregulation of PTEN and increase in beta cell proliferation in that group. Our studies demonstrated that miR-216a could serve as a potential therapeutic target for the treatment of diabetes. miR-216a-targeting theranostic nanodrugs served as exploratory tools to define functionality of this miRNA in conjunction with in vivo MR imaging.

Chronic pancreatitis (CP) is a complex disease that should be treated by experienced teams of gastroenterologists, radiologists, surgeons, and nutritionists in a multidisciplinary environment. Medical treatment includes lifestyle modification, nutrition, exocrine and endocrine pancreatic insufficiency correction, and pain management. Up to 60% of patients will ultimately require some type of endoscopic or surgical intervention for treatment. However, regardless of the modality, they are often ineffective unless smoking and alcohol cessation is achieved. Surgery retains a major role in the treatment of CP patients with intractable chronic pain or suspected pancreatic mass. For other complications like biliary or gastroduodenal obstruction, pseudocyst drainage can be performed endoscopically. The recommendations for CP were developed by Clube Português do Pâncreas (CPP), based on literature review to answer predefined topics, subsequently discussed and approved by all members of CPP. Recommendations are separated in two parts: "chronic pancreatitis etiology, natural history, and diagnosis," and "chronic pancreatitis medical, endoscopic, and surgical treatment." This abstract pertains to part II.

In recent years, with the development of biological materials, the types and clinical applications of stents have been increasing in pancreatic diseases. However, relevant problems are also constantly emerging. Our purpose was to summarize current hotspots and explore potential topics in the fields of the application of stent implantation in the treatment of pancreatic diseases for future scientific research.

Publications on the application of stents in pancreatic diseases were retrieved from PubMed without language limits. High-frequency Medical Subject Headings (MeSH) terms were identified through Bibliographic Item Co-Occurrence Matrix Builder (BICOMB). Biclustering analysis results were visualized utilizing the gCLUTO software. Finally, we plotted a strategic diagram.

A total of 4,087 relevant publications were obtained from PubMed until May 15th, 2018. Eighty-three high-frequency MeSH terms were identified. Biclustering analysis revealed that these high-frequency MeSH terms were classified into eight clusters. After calculating the density and concentricity of each cluster, strategy diagram was presented. The cluster 5 "complications such as pancreatitis associated with stent implantation" was located at the fourth quadrant with high centricity and low density.

In our study, we found eight topics concerning the application of stent implantation in the treatment of pancreatic diseases. How to reduce the incidence of postoperative complications and improve the prognosis of patients with pancreatic diseases by stent implantation could become potential hotspots in the future research.

Endoscopic treatment of pancreatic ductal malformations causing recurrent acute pancreatitis, such as pancreas divisum or ansa pancreatica, is mainly based on the sphincterotomy of the minor papilla. However, the technical complexity of conventional endoscopic retrograde cholangiopancreatography (ERCP) is increased in patients presenting anatomical variants like these and it may be unsuccessful. We report the case of a pancreas divisum combined with ansa pancreatica and describe the cannulation and sphincterotomy of the minor papilla using an ultrasound-assisted Rendez-Vous technique.

Endoscopic retrograde cholangiopancreatography (ERCP) is an adjunct for pediatric pancreatic injury management, but its use and utility in pediatric patients are unclear. We set out to evaluate the use of ERCP and its effects on outcomes.

A retrospective review was performed for children who had pancreatic injuries at 22 pediatric trauma centers between 2010 and 2015. ERCP details and outcomes were collected. Analysis was performed using descriptive statistics and Wilcoxon rank-sum tests.

ERCP was used at 14/22 centers for 26 patients. Indications were duct evaluation, duct leak control, pseudocyst, fistula, and stricture. ERCP altered management or improved outcomes in 13/26 (50%), most commonly in patients with ERCP for duct evaluation, stricture, and fistula. In patients managed nonoperatively, those with early endoscopic intervention (within one week of injury) with stent or sphincterotomy (n=9) had similar time to regular diet [median (IQR)]: [10 (7-211) vs 7 (4-12) days; p=0.55], similar hospital days: [12 (8-20) vs 11 (6-19) days, p=0.63], and similar time on parenteral nutrition: [17 (10-40) vs 10 (6-18) days; p=0.19] compared to patients who were only observed.

In children with blunt pancreatic injury, ERCP can be useful to diagnose duct injury and for management of late complications such as stricture and fistula. However, early endoscopic intervention for pancreatic duct disruption may not improve outcome or expedite recovery. Further study is needed.

Retrospective Study; Treatment Study.

III.

Critical review of the indications for total pancreatectomy and highlight limitations in current diagnostic criteria for chronic pancreatitis.

The diagnosis of noncalcific chronic pancreatitis remains controversial because of an overreliance on nonspecific imaging and laboratories findings. Endoscopic ultrasound, s-magnetic resonance cholangiopancreatography, and/or endoscopic pancreatic function testing are often used to diagnose noncalcific chronic pancreatitis despite the fact that there is no gold standard for this condition. Abdominal pain is not specific for chronic pancreatitis and is more likely to be encountered in patients with functional gastrointestinal disorders based on the high incidence of these conditions. The duration of pain and opioid analgesic use results in central sensitization that adversely affects pain outcomes after total pancreatectomy. An alcoholic cause is associated with poorer pain outcomes after total pancreatectomy.

The lack of a gold standard for noncalcific chronic pancreatitis limits the diagnostic accuracy of imaging and laboratory tests. The pain of chronic pancreatitis is nonspecific and is affected by duration, preoperative opioid use, and cause. These factors will need to be considered in the development of future selection criteria for this morbid surgery.

Recently, the novel SpyGlass DS Direct Visualization system (SPY DS) has become available. This system offers several advantages over the conventional SPYGlass system. This study evaluated the clinical feasibility and efficacy of diagnostic and therapeutic procedures for biliary disorder using SPY DS.In this retrospective study, consecutive patients who had biliary disorder were enrolled between November 2015 and February 2016. All patients could not be diagnosed or treated by standard endoscopic retrograde cholangiopancreatography in our hospital or at another hospital.A total of 28 consecutive patients (21 men and 7 women; median age, 73 years; age range, 55-87 years) were retrospectively enrolled in this study. Among them, diagnostic procedure was performed in 20 patients, and 8 patients underwent therapeutic procedures. The technical success rate for diagnostic procedures was 100% (20/20). Diagnostic accuracy was 100% (19/19). The technical success rate for therapeutic procedures was 88% (7/8). Among these 8 patients, 4 patients with common bile duct stones underwent electrohydraulic lithotripsy. One patient successfully underwent guidewire insertion to remove a migrated plastic stent. The 3 remaining patients underwent SPY DS to insert a guidewire for left bile duct obstruction and for posterior bile duct branch. In the patient who underwent guidewire insertion for left hepatic bile duct obstruction cause by primary sclerosing cholangitis, we could not advance the guidewire into the left hepatic bile duct. No adverse events were seen. Median SPY DS insertion time was 21 min (range, 8-32 min).Single-operator cholangioscopy using SPY DS was feasible and had a marked clinical impact in patients with biliary disease. Additional case reports and prospective studies are needed to examine further applications of this system.