Safety and efficacy of endoscopic ultrasound-guided pancreatic duct drainage using a drill dilator: a retrospective study from Japan.

Background/Aims: Dilation of the tract before stent deployment is a challenging step in endoscopic ultrasound-guided pancreatic duct drainage (EUS-PDD). In this study, we examined the effectiveness and safety of a novel spiral dilator, Tornus ES (Asahi Intec), for EUS-PDD. Methods: This was a retrospective, single-arm, observational study at Aichi Cancer Center Hospital. The punctured tract was dilated using a Tornus ES dilator in all EUS-PDD cases. Our primary endpoint was the technical success rate of initial tract dilation. Technical success was defined as successful fistula dilation using Tornus ES followed by successful stent insertion. Secondary endpoints were procedure times and early adverse events. Results: A total of 12 patients were included between December 2021 and March 2023. EUS-PDD was performed in 11 patients for post-pancreaticoduodenectomy anastomotic strictures and one patient with pancreatitis with duodenal perforation. The technical success rates of stent insertion and fistula dilation using Tornus ES dilator was 100%. The median procedure time was 24 minutes. No remarkable adverse events related to the procedure were observed, apart from fever, which occurred in 2 patients. Conclusions: Tract dilation in EUS-PDD using Tornus ES is effective and safe.

Early diagnosis of pancreatic cancer: Shedding light on an unresolved challenge.

Diagnosing early-stage pancreatic cancer (PC) remains a clinical challenge. Hence, studying novel imaging aspects that could enhance the diagnostic accuracy of malignant pancreatic precursor lesions is imperative. This article aims to underscore the promising role of emerging imaging aspects that may facilitate the earlier diagnosis of PC, thereby improving its management and prognosis.

CFTR function is impaired in a subset of patients with pancreatitis carrying rare CFTR variants.

BACKGROUND: Many affected by pancreatitis harbor rare variants of the cystic fibrosis (CF) gene, CFTR, which encodes an epithelial chloride/bicarbonate channel. We investigated CFTR function and the effect of CFTR modulator drugs in pancreatitis patients carrying CFTR variants. METHODS: Next-generation sequencing was performed to identify CFTR variants. Sweat tests and nasal potential difference (NPD) assays were performed to assess CFTR function in vivo. Intestinal current measurement (ICM) was performed on rectal biopsies. Patient-derived intestinal epithelial monolayers were used to evaluate chloride and bicarbonate transport and the effects of a CFTR modulator combination: elexacaftor, tezacaftor and ivacaftor (ETI). RESULTS: Of 32 pancreatitis patients carrying CFTR variants, three had CF-causing mutations on both alleles and yielded CF-typical sweat test, NPD and ICM results. Fourteen subjects showed a more modest elevation in sweat chloride levels, including three that were provisionally diagnosed with CF. ICM indicated impaired CFTR function in nine out of 17 non-CF subjects tested. This group of nine included five carrying a wild type CFTR allele. In epithelial monolayers, a reduction in CFTR-dependent chloride transport was found in six out of 14 subjects tested, whereas bicarbonate secretion was reduced in only one individual. In epithelial monolayers of four of these six subjects, ETI improved CFTR function. CONCLUSIONS: CFTR function is impaired in a subset of pancreatitis patients carrying CFTR variants. Mutations outside the CFTR locus may contribute to the anion transport defect. Bioassays on patient-derived intestinal tissue and organoids can be used to detect such defects and to assess the effect of CFTR modulators.

Acinar-ductal cell rearrangement drives branching morphogenesis of the murine pancreas in an IGF/PI3K-dependent manner.

During organ formation, progenitor cells need to acquire different cell identities and organize themselves into distinct structural units. How these processes are coordinated and how tissue architecture(s) is preserved despite the dramatic cell rearrangements occurring in developing organs remain unclear. Here, we identified cellular rearrangements between acinar and ductal progenitors as a mechanism to drive branching morphogenesis in the pancreas while preserving the integrity of the acinar-ductal functional unit. Using ex vivo and in vivo mouse models, we found that pancreatic ductal cells form clefts by protruding and pulling on the acinar basement membrane, which leads to acini splitting. Newly formed acini remain connected to the bifurcated branches generated by ductal cell rearrangement. Insulin growth factor (IGF)/phosphatidylinositol 3-kinase (PI3K) pathway finely regulates this process by controlling pancreatic ductal tissue fluidity, with a simultaneous impact on branching and cell fate acquisition. Together, our results explain how acinar structure multiplication and branch bifurcation are synchronized during pancreas organogenesis.

Endoscopic retrograde cholangiopancreatography for diagnosing and treating pediatric biliary and pancreatic diseases.

BACKGROUND: This study evaluated the safety and effectiveness of endoscopic retrograde cholangiopancreatography (ERCP) in pediatric patients with biliary and pancreatic diseases. A retrospective analysis was conducted on 57 ERCP procedures performed in 41 children, primarily for treating pancreatic diseases. The overall success rate was 91.2%, with no major complications observed. Post-ERCP pancreatitis (PEP) occurred in 8.8% of cases. Follow-up examinations over one year showed no recurrence of biliary or pancreatic diseases. Notably, endoscopic treatment led to a significant increase in body mass index (BMI). These findings demonstrate the valuable role of ERCP in managing such conditions. AIM: To evaluate the safety and efficacy of ERCP for the management of biliary and pancreatic diseases in pediatric patients. METHODS: We conducted a retrospective analysis of data from children aged 1-18 years who underwent ERCP for biliary and pancreatic diseases at Beijing Children's Hospital between January 2021 and December 2022. The collected data included procedure time, endoscopic treatment, success rate, and postoperative complications. RESULTS: Forty-one children underwent 57 ERCP procedures, including 14 with biliary duct disease and 27 with pancreatic disease. The mean age of the patients was 7.48 ± 3.48 years. Biliary duct-related treatments were performed 18 times, and pancreatic disease treatments were performed 39 times. ERCP was primarily used to treat pediatric pancreatic diseases [68.4% (39/57) of the procedures]. The overall success rate was 91.2% (52/57 patients). PEP was noted in five patients (8.8%, 5/57), and no instances of bleeding, perforation, or cholangitis were observed. The patients were followed up for over one year, and no recurrence of biliary or pancreatic diseases was detected. Importantly, BMI significantly increased after endoscopic treatment compared to that before treatment (P = 0.001). CONCLUSION: The high success rate and lack of major complications support the valuable role of ERCP in the management of pediatric biliary and pancreatic diseases in the pediatric population.

Inversin-deficient (inv) mice do not establish a polarized duct system in the liver and pancreas.

Inversin-deficient (inv) mice have anomalies in liver and pancreatic development in addition to an inverted left-right axis of the body. The present study was undertaken to unveil mechanisms of bile and pancreatic duct development from immunohistochemical analyses of anomalies in inv mice. Intrahepatic bile ducts having proximodistal polarity in size and the height of their epithelia, and ductules were formed in livers of wild-type neonates. By contrast, in inv mice, ductal plates, precursor structures of intrahepatic bile ducts and ductules, persisted without the proximodistal polarity. Their epithelial cells did not acquire planar cell polarity (PCP) in terms of expression of tight junction proteins although they expressed bile duct markers, HNF1ß and SOX9. They had an apicobasal polarity from expression of basal laminar components. Enlargement of the hepatic artery and poor connective tissue development, including the abnormal deposition of the extracellular matrices, were also noted in inv mice, suggesting that bile duct development was coupled to that of the hepatic artery and portal vein. In pancreata of inv neonates, neither the main pancreatic duct was formed, nor dilated duct-like structures had the morphological polarity from the connecting point with the common bile duct. Lumina of acini was dilated, and centroacinar cells changed their position in the acini to their neck region. Immunohistochemical analyses of tight junction proteins suggested that epithelial cells of the duct-like structures did not have a PCP. Thus, Invs may be required for the establishment of the PCP of the whole duct system in the liver and pancreas.

Is Endoscopy Mandatory In Cases Mimicking Acute Pancreatitis?

Objectives: To detect the utility of nonspecific rising of pancreatic enzymes in patients with stomach discomfort, and to explore the possibility of hyperamylasemia as a differential diagnosis. Method: The cross-sectional study was conducted from April 2020 to April 2021 at two large tertiary care centres in Kafrelsheikh and Zagazig governorates in northern Egypt, and comprised patients complaining of dull aching abdominal pain. They were classified into two groups. Patients with nonspecific rise in pancreatic enzymes less than threefold in the absence of acute pancreatitis were in group I, while those having abdominal pain without rise in pancreatic enzymes were in group II. All patients were subjected to detailed history and clinical examination followed by laboratory assessment, imaging studies and upper endoscopy. Data was analysed using SPSS 20. RESULTS: Of the 270 patients, 170(63%) were in group I; 120(70.5%) males and 50(29.5%) females with mean age 51±6.58 years, There were 100(37%) patientsin group II; 65(65%) males and 35(35%) females with mean age 53±8.96 years (p>0.05). Amylase, lipase, serum glutamic-oxaloacetic transaminase, serum glutamic-pyruvic transaminase, Creactive protein and helicobacter pylori values were significantly different between the groups (p<0.05). CONCLUSIONS: Elevation of pancreatic enzymes with a level less than three-fold in patients with abdominal pain reflected mucosal injury of the gastrointestinal tract and may raise the necessity for diagnostic upper endoscopy.

Lymphocytes regulate expression of the SARS-CoV-2 cell entry factor ACE2 in the pancreas of T2DM patients.

AIMS: COVID-19 patients with type 2 diabetes mellitus (T2DM) show both poorer clinical outcomes and have an increased risk of death. SARS-CoV-2 virus infection requires simultaneous expression of the SARS-CoV-2 cell entry factors angiotensin-converting enzyme 2 (ACE2) and transmembrane protease serine type 2 (TMPRSS2) in the same cell. The aim of the study was to explore the underlying mechanisms of a COVID-19 infection in patients with T2DM. METHODS: The distribution and expression of AEC2 and TMPRSS2 in different pancreatic cell types in clinical samples of T2DM patients and diabetic mouse models were analysed by single-cell sequencing, bioinformatics analysis and basic experiments. RESULTS: The results showed that ACE2 and TMPRSS2 are expressed in the ducts of the human pancreas. These findings suggest that SARS-CoV-2 can infect ductal cells in vivo through ACE2 and TMPRSS2. T2DM can promote the co-expression of ACE2 and TMPRSS2 in exocrine ducts, including in the human pancreas. We hypothesize that ACE2 expression levels are associated with increased numbers of lymphocytes in vivo. CONCLUSIONS: Increased blood glucose levels are associated with increased ACE2 expression and an increased number of lymphocytes. At the same time, lymphocytes can promote ACE2 expression.

The effectiveness of endoscopic ultrasonography findings to distinguish benign and malignant intraductal papillary mucinous neoplasm.

BACKGROUND AND AIMS: Accurate evaluation of intraductal papillary mucinous neoplasm (IPMN) is necessary to inform clinical decision-making. But it is still difficult to distinguish benign and malignant IPMN preoperatively. This study aims to evaluate the utility of EUS to predict the pathology of IPMN. METHODS: Patients with IPMN who underwent endoscopic ultrasound within 3 months before surgery were collected from six centers. Logistic regression model and random forest model were used to determine risk factors associated with malignant IPMN. In both models, 70% and 30% of patients were randomly assigned to the exploratory group and validation group, respectively. Sensitivity, specificity, and ROC were used in model assessment. RESULTS: Of the 115 patients, 56 (48.7%) had low-grade dysplasia (LGD), 25 (21.7%) had high-grade dysplasia (HGD), and 34 (29.6%) had invasive cancer (IC). Smoking history (OR = 6.95, 95%CI: 1.98-24.44, p = 0.002), lymphadenopathy (OR = 7.91, 95%CI: 1.60-39.07, p = 0.011), MPD > 7 mm (OR = 4.75, 95%CI: 1.56-14.47, p = 0.006) and mural nodules > 5 mm (OR = 8.79, 95%CI: 2.40-32.24, p = 0.001) were independent risk factors predicting malignant IPMN according to the logistic regression model. The sensitivity, specificity, and AUC were 0.895, 0.571, and 0.795 in the validation group. In the random forest model, the sensitivity, specificity, and AUC were 0.722, 0.823, and 0.773, respectively. In patients with mural nodules, random forest model could reach a sensitivity of 0.905 and a specificity of 0.900. CONCLUSIONS: Using random forest model based on EUS data is effective to differentiate benign and malignant IPMN in this cohort, especially in patients with mural nodules.

Fractured guide wire in the main pancreatic duct during ERCP: A case report.

INTRODUCTION: Endoscopic retrograde cholangiopancreatography (ERCP) is an excellent endoscopic method with a wide range of diagnostic and therapeutic utility. The most common complication is post-ERCP pancreatitis with a reported incidence of 3.5 % followed by cholangitis, cholecystitis, gastrointestinal bleeding and duodenal perforation. Uncommon complications of the procedure reported in the literature include contrast allergy, cardio-pulmonary compromise, problems related to instruments such as impaction of a retrieval basket, fractured guidewire in the biliary or pancreatic channel, extravasation of contrast medium into the duodenal wall, splenic hemorrhage, hepatic trauma and complications related to the electrosurgical risk. PRESENTATION OF CASE: We present a case of a 37-year old woman referred to the Department of Abdominal Surgery because of severe abdominal pain and jaundice. Medical personal history of the patient was normal and she denied taking any medication. Following radiological and laboratory analysis, ERCP was completed. In our first attempt to selectively cannulate the CBD, unintentionally a guide wire passed in the main pancreatic duct. Attempting to retract the guide wire under fluoroscopy surveillance, the guide wire was fractured and fragments were left in the main pancreatic duct. Removal of the fragments was unsuccessful in several attempts. Consecutively, selective cannulation of the main pancreatic duct with placement of the pancreatic stent 5Fr/5cm was performed and careful cannulation of CBD was achieved. After the sphincterotomy, the biliary sludge and microlites were dispatched into the duodenum. The pancreatic stent was removed seven days later and patient underwent cholecystectomy four months later. No complications related to the procedure were revealed during the 24 months of follow-up. DISCUSSION: A fractured guide-wire during the ERCP is an uncommon event that can occur during the selective cannulation of the common bile duct or pancreatic duct as in our presented case. However, data regarding the guidewire fracture during the ERCP are scarce since it is an uncommon occurrence. Our case is an example of rare and unusual complication during the ERCP, which was managed conservatively at our unit. Based on our research successful retrievals of the fractured guidewire from the main pancreatic duct are rarely reported and we found only two cases in the available literature. Concordantly with our case, acute and long-term pancreatico-biliary complications were not reported in previously published case reports with retained guide wire during the ERCP as we found only one case report in which authors report development of cholangitis related to the fracture of the hydrophilic guidewire. However, rare but serious life-threatening complications that can occur during the ERCP procedure should be identified in a timely manner and treated accordingly. CONCLUSION: Fractured guide wire during the ERCP is very uncommon complication of the procedure with only few cases reported in the literature. Our experience suggests that no adverse sequels were triggered by the wire pieces left in the main pancreatic duct as the patient remained asymptomatic 2 years after the guide wire fracture.

Spontaneous healing after conservative treatment of isolated grade IV pancreatic duct disruption caused by trauma: A case report.

BACKGROUND: Trauma is a common cause of pancreatic duct disruption. Surgical treatment is recommended in current clinical guidelines for adult pancreatic injury because non-surgical treatments have higher risks of serious complications or even death compared with surgical treatment. CASE SUMMARY: A 22-year-old woman was admitted to Tiantai People's Hospital of Zhejiang Province after 1-h duration of abdominal pain and distension following trauma. The diagnosis was "traumatic pancreatic rupture". The patient's symptoms were not severe, her vital signs were stable, and signs of peritonitis were not obvious. Therefore, conservative treatment could be considered, with the possibility of emergency surgery if necessary. After 2 mo of conservative treatment with duct drainage, the pancreatic duct healed spontaneously with no significant complications. CONCLUSION: We report a case of pancreatic duct disruption in the head and neck caused by trauma that was treated conservatively and healed spontaneously, providing a new choice for clinical practice. For isolated pancreatic injury with rupture of the pancreatic duct in the head and neck, conservative treatment under close observation is feasible.

Basic Pancreatic Lesions: Radiologic-pathologic Correlation.

The basic pancreatic lesions include location, size, shape, number, capsule, calcification/calculi, hemorrhage, cystic degeneration, fibrosis, pancreatic duct alterations, and microvessel. One or more basic lesions form a kind of pancreatic disease. As recognizing the characteristic imaging features of pancreatic basic lesions and their relationships with pathology aids in differentiating the variety of pancreatic diseases. The purpose of this study is to review the pathological and imaging features of the basic pancreatic lesions.

Assessment of main pancreatic duct cutoff with dilatation, but without visible pancreatic focal lesion on MDCT: a novel diagnostic approach for malignant stricture using a CT-based nomogram.

OBJECTIVES: To identify useful features to predict hidden pancreatic malignancies in patients with main pancreatic duct (MPD) abrupt cutoff and dilatation, but without visible focal pancreatic lesions on CT. METHODS: This retrospective study included 92 patients (mean age, 63.4 ± 10.6 years, 63 men and 29 women) with MPD abrupt cutoff and dilatation, but without visible focal pancreatic lesion on contrast-enhanced CT between 2009 and 2021. Two radiologists independently evaluated the CT imaging features. Multivariable logistic regression analysis was performed to identify clinical and CT imaging features for hidden pancreatic malignancies. A nomogram was developed based on these results and assessed its performance. RESULTS: Thirty-eight (41.3%) and 54 (58.7%) were classified into the malignant and benign groups, respectively. In the multivariable analysis, CA19-9 elevation (odds ratio [OR] 7.5, p = 0.003), duct cutoff site at the head/neck (OR 7.6, p = 0.006), parenchymal contour abnormality at the duct cutoff site (OR 13.7, p < 0.001), and presence of acute pancreatitis (OR 11.5, p = 0.005) were independent predictors of pancreatic malignancy. A combination of any two significant features showed an accuracy of 77.2%, and a combination of any three features exhibited a specificity of 100%. The CT-based nomogram showed an area under the curve (AUC) of 0.84 (95% confidence interval, 0.77-0.90). CONCLUSIONS: The three CT imaging features and CA19-9 elevation translated into a nomogram permit a reliable estimation of hidden pancreatic malignancies in patients with MPD abrupt cutoff without visible focal pancreatic lesion. It may facilitate determining whether to proceed to further diagnostic tests. KEY POINTS: • Isoattenuating pancreatic ductal adenocarcinoma can manifest only as an isolated main pancreatic duct (MPD) dilatation with abrupt cutoff, making it difficult to distinguish from benign strictures. • Along with the serum CA 19-9 elevation, MPD cutoff site at the pancreas head or neck, parenchymal contour abnormality at the duct cutoff site, and associated acute pancreatitis indicated a higher probability of the malignant MPD strictures. • The CT-based nomogram provided excellent diagnostic performance (AUC of 0.84) for hidden pancreatic malignancies in patients with MPD abrupt cutoff and dilatation.

Abbreviated non-enhanced magnetic resonance imaging in patients with acute necrotizing pancreatitis.

AIM: To investigate the performance of T2-weighted abbreviated magnetic resonance imaging (T2W-AMRI) protocol in evaluating patients with acute necrotizing pancreatitis (ANP). METHODS: A retrospective analysis of consecutive hospitalized patients with ANP who underwent MRI (contrast-enhanced, CE or non-contrast, NC) between January 2017 and November 2020 was performed. The T2W-AMRI and complete MRI (cMRI) sequences were anonymized, and subsequently, two separate sets of data (AMRI and cMRI) were created for presentation to the radiologists involved in reading the data. The T2W-AMRI was based on a single-axial T2 half-Fourier acquisition single-shot turbo spin-echo (HASTE) sequence. The pancreatic and extrapancreatic findings were recorded and tabulated independently by two radiologists on T2W-AMRI and cMRI. In addition, the interobserver agreement and association of findings between T2W-AMRI and cMRI were analyzed. RESULTS: Twenty-eight patients (mean age 31.7 ± 12.2 years, 17 females) were included. Thirteen patients had CE-cMRI, while the rest underwent NC-cMRI. There was no significant difference in the identification of pancreatic necrosis on T2W-AMRI vs. cMRI (p = 1.00). However, T2W-AMRI underestimated necrosis in one patient. Collections were accurately detected in all patients on T2W-AMRI. The mean size of the collection was larger on cMRI (6.5 ± 3.7 cm) than T2W-AMRI (6 ± 3.7 cm) with p = 0.006. cMRI detected more patients with disrupted pancreatic duct (n = 9) than T2W-AMRI (n = 6). However, the difference was not statistically significant (p = 0.375). There was a good to an excellent interobserver agreement between the readers for T2W-AMRI (k = 0.62-1). CONCLUSION: T2W-AMRI may offer a suitable alternative to cMRI in ANP, especially severe disease, as it can be acquired rapidly without the need for contrast injection.

Acute pancreatitis secondary to ansa pancreatica: Two new cases and review of the literature.

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.

Obstructive Jaundice Caused by a Large Intact Abdominal Aortic Aneurysm. Case Report and Literature Review.

BACKGROUND: Obstructive jaundice caused by abdominal aortic aneurysm (AAA) is an extremely rare clinical presentation. We present an 85-year-old male with a large intact AAA causing obstructive jaundice and review the relevant literature. METHODS AND RESULTS: The patient was referred to our hospital with jaundice and a palpable pulsatile abdominal mass. Computerized tomography (CT) angiogram and magnetic resonance cholangiopancreatography (MRCP) revealed an infrarenal AAA with maximal diameter of 8.5 cm compressing the pancreatic head and common bile duct, causing obstructive jaundice with elevated levels of total, and direct bilirubin. The patient was subjected to endovascular aneurysm repair (EVAR). Blood bilirubin gradually decreased to normal levels. No complications were reported during the immediate postoperative and at 3-month follow up period. Literature review suggests that our case is one of the largest intact AAAs which have been reported to cause biliary obstruction. CONCLUSIONS: AAAs causing secondary obstructive jaundice is an uncommon clinical presentation requiring high clinical suspicion during differential diagnosis, so that patients can receive proper and early diagnosis and treatment.

Endoscopic ultrasound-guided pancreatic sampling for the histopathological diagnosis of autoimmune pancreatitis.

Autoimmune pancreatitis (AIP), which is characterized by pancreatic enlargement and irregular narrowing of the main pancreatic duct, is difficult to differentiate from malignancy. The irregular narrowing of the pancreatic duct, which can be detected via endoscopic retrograde cholangiopancreatography, is a characteristic feature of AIP; however, distinguishing between localized AIP and pancreatic cancer based on pancreatic duct imaging is difficult. This study overviews the efficacy of endoscopic ultrasound (EUS)-guided pancreatic sampling for the histopathological diagnosis of AIP. Recent enhancements in needle biopsy methodologies and technologies have contributed to improvement in the diagnostic efficacy of this technique. The guidance provided in this study for the histological diagnosis of AIP is anticipated to further advance in the histopathological diagnosis of AIP using EUS-guided pancreatic sampling.