miR-605-3p may affect caerulein-induced ductal cell injury and pyroptosis in acute pancreatitis by targeting the DUOX2/NLRP3/NF-κB pathway.

Acute pancreatitis (AP) is a sudden-onset disease of the digestive system caused by abnormal activation of pancreatic enzymes. Dual oxidase 2 (DUOX2) has been found to be elevated in the progression of a variety of inflammatory diseases. Therefore, we analyzed the specific roles of DUOX2 in AP development. Blood samples were collected from of AP patients and healthy people, and the caerulein- stimulated human pancreatic duct cells (H6C7) were utilized to establish an AP cell model. Cell growth and apoptosis were measured using an MTT assay and TUNEL staining. Additionally, RT-qPCR and western blot assays were conducted to assess the RNA and protein expressions of the cells. ELISA kits were used to determine TNF-α, IL-6, IL-8, and IL-1ß levels. The interaction between DUOX2 and miR-605-3p was predicted using the Targetscan database and confirmed by dual-luciferase report assay. We found that DUOX2 increased while miR-605-3p decreased in the blood of AP patients and caerulein-stimulated H6C7 cells. DUOX2 was targeted by miR-605-3p. Furthermore, DUOX2 knockdown or miR-605-3p overexpression promoted cell viability, decreased the TNF-α, IL-6, IL-8, and IL-1ß levels, and inhibited apoptosis rate in caerulein-stimulated H6C7 cells. DUOX2 knockdown or miR-605-3p overexpression also increased the Bcl-2 protein levels and down-regulated Bax, cleaved-caspase-1, NLRP3 and p-p65. Interestingly, DUOX2 overexpression reversed the miR-605-3p mimic function in the caerulein-treated H6C7 cells. In conclusion, our research demonstrated that DUOX2 knockdown relieved the injury and inflammation in caerulein-stimulated H6C7 cells.

Main pancreatic duct involved IPMN without high-risk factors: how to judge the degree of malignancy based on MPD dilation?

The aim of this study was to evaluate the cutoff value for identifying malignance in main pancreatic duct (MPD)-involved intraductal papillary mucinous neoplasm (IPMN) with an MPD diameter ranging from 5 to 10 mm. Clinical-radiological characteristics of 142 patients, including MPD-involved IPMNs (n = 53) and branch-duct (BD)-IPMNs (n = 89) were analyzed. Logistic regression analysis was used to determine the risk factors of malignant IPMNs and invasive carcinoma. ROC curves were used to identify different cutoffs in terms of preoperative MPD values to predict the presence of invasive carcinoma as well as malignant IPMNs, and the prediction performance was evaluated. For MPD-involved IPMNs (5 mm < MPD < 10 mm), MPD diameter of 7.5 mm for discriminating malignant IPMNs (area under curve [AUC] = 0.67) and 7.7 mm for discriminating invasive IPMNs (AUC = 0.56) were found to be the optimal cutoff values at receiver operating characteristic curve (ROC) analysis. MPD > 7.5 mm and carbohydrate antigen19-9 (Ca19-9) > 37 U/ml were found to be predictors of malignant IPMNs at univariate, and MPD > 7.5 mm was a predictor in multivariate analysis in MPD-involved IPMNs. The AUC of the ROC curve of MPD (7.5 mm) combined with Ca19-9 in identifying malignant IPMNs was 0.73 in MPD-involved IPMNs. MPD (7.5 mm) combined with Ca19-9 performed well in identifying malignant IPMNs in MPD-involved IPMNs.

X-Box binding protein 1 downregulates SIRT6 to promote injury in pancreatic ductal epithelial cells.

OBJECTIVE: Acute pancreatitis (AP) stands as a frequent cause for clinical emergency hospital admissions. The X-box binding protein 1 (XBP1) was found to be implicated in pancreatic acinar cell apoptosis. The objective is to unveil the potential mechanisms governed by XBP1 and SIRT6 in the context of AP. METHODS: Caerulein-treated human pancreatic duct epithelial (HPDE) cells to establish an in vitro research model. The levels and regulatory role of SIRT6 in the treated cells were evaluated, including its effects on inflammatory responses, oxidative stress, apoptosis, and endoplasmic reticulum stress. The relationship between XBP1 and SIRT6 was explored by luciferase and ChIP experiments. Furthermore, the effect of XBP1 overexpression on the regulatory function of SIRT6 on cells was evaluated. RESULTS: Caerulein promoted the decrease of SIRT6 and the increase of XBP1 in HPDE cells. Overexpression of SIRT6 slowed down the secretion of inflammatory factors, oxidative stress, apoptosis level, and endoplasmic reticulum stress in HPDE cells. However, XBP1 negatively regulated SIRT6, and XBP1 overexpression partially reversed the regulation of SIRT6 on the above aspects. CONCLUSION: Our study illuminates the role of XBP1 in downregulating SIRT6 in HPDE cells, thereby promoting cellular injury. Inhibiting XBP1 or augmenting SIRT6 levels holds promise in preserving cell function and represents a potential therapeutic avenue in the management of AP.

Endoscopic ultrasound-guided pancreatic duct drainage: a comprehensive state of the art review.

INTRODUCTION: Endoscopic retrograde pancreatography (ERP) has traditionally been the standard modality for pancreatic endotherapy. However, in certain situations, failure of retrograde ductal access may warrant an alternative modality of drainage. This can occur in various settings like difficult and/or surgically altered anatomy or duodenal obstruction. Endoscopic ultrasound-guided pancreatic duct drainage (EUS-PDD) is a relatively newer addition to the armamentarium for endoscopic access to the PD. AREAS COVERED: This comprehensive state-of-art review aims to give an overview of the indications, technical details, different approaches, and outcomes of EUS-PDD, with the latest evidence available in scientific literature. EXPERT OPINION: Akin to its biliary drainage counterpart, EUS-PDD enables an EUS-assisted-ERP using rendezvous technique or EUS-guided drainage through transmural stenting. The technique has evolved over the ensuing years with multitude of accessories, approaches, and devices to optimize the outcomes. However, the technical success and adverse events rates need to be further improved. Additionally, it has a steep learning curve with requirements of advanced technical skill and optimum infrastructure back-up. Meticulous patient selection, precise knowledge of ductal anatomy, appropriate approach, and carefully chosen accessories can improve its clinical outcomes.

Prophylactic pancreatic duct stenting to reduce the risk of post-ampullectomy pancreatitis: a comprehensive review and meta-analysis of 1858 patients.

BACKGROUND: The effectiveness of prophylactic pancreatic duct stenting (PPDS) in preventing post-ampullectomy pancreatitis (PAP) at the time of endoscopic ampullectomy (EA) has been reported, however, results are conflicting. We conducted a systematic review and meta-analysis looking at the use of PPDS in reducing PAP as well as overall post-ampullectomy complications. METHODS: Multiple databases were searched through May 2023 for studies reporting on EA. Meta-analysis was performed to determine pooled proportions and relative risk (RR) with 95% confidence intervals (CI) of PAP, with and without PPDS. Pooled rates of adverse events including perforation, delayed bleeding, cholangitis, and procedure related mortality were assessed. Random effects model was used for our meta-analysis and heterogeneity was assessed using the I2 statistics. RESULTS: Thirty-four studies (14 case series, 18 cohort studies and 2 randomized controlled trials) with 1868 patients were included. The overall pooled rate of PAP was 12.3% (CI 10.3-14.5). We found no statistically significant difference in rates of PAP among patients with PPDS, 11.9% (CI 8.9-15.7) and without PPDS, 16.6% (CI 13.4-20.4), RR 0.8 (CI 0.51-1.28), p = 0.4. In terms of severe PAP, we found no difference between the two groups. The overall pooled rates of successful en-bloc and piecemeal resection were 74.8% (CI 67.3-81.1) and 25.1% (CI 19-32.4). Additionally, pooled rates of ampullary stenosis, post procedural bleeding, perforation, cholangitis, and procedure related mortality were 3.6%, 11.1%, 4.2%, 3.5%, and 1.3%, respectively. CONCLUSIONS: Our analysis shows that PPDS at the time of EA does not offer a significant protective effect against PAP. While the incidence of PAP was higher among the no PPDS group, it is plausible that this is more likely due to variation among studies in terms of lesion size, length/size of pancreatic stent used and etiology of ampullary lesions. Future well-designed randomized controlled trials are needed to validate our findings.

Tumor fibroso calcificante intestinal: reporte de caso / Intestinal calcifying fibrous tumor: case report

El tumor fibroso calcificante (TFC) es una inusual lesión benigna de origen mesenquimal que puede presentar características similares a otros tumores más comunes. El caso involucra a una mujer de 36 años con un tumor en el yeyuno proximal, inicialmente sospechoso de ser un tumor del estroma gastrointestinal (GIST). Se realiza una resección quirúrgica, revelando un nódulo bien delimitado en el borde antimesentérico con características microscópicas típicas de TFC. Las células tumorales presentaban positividad para CD34 y negatividad para demás marcadores, diferenciándolo de otras neoplasias. El TFC puede confundirse con tumores más comunes debido a su apariencia, pero un diagnóstico preciso respaldado por inmunohistoquímica es esencial. La extirpación quirúrgica completa suele ser curativa. (AU)

Calcifying fibrous tumor (CFT) is a rare benign lesion of mesenchymal origin that may present similar characteristics to other more common tumors. We present the case of a 36-year-old woman with a tumor in the proximal jejunum, initially suspected to be a gastrointestinal stromal tumor (GIST). Surgical resection was performed, revealing a well-demarcated nodule at the anti-mesenteric border with microscopic features typical of a calcifying fibrous tumor. The tumor cells were positive for CD34 and negative for other markers, differentiating it from other neoplasms. Calcifying fibrous tumors can be confused with more common tumors because of its appearance, but an accurate diagnosis supported by immunohistochemistry is essential. Complete surgical excision is usually curative. (AU)

Diagnosis of pancreatic malignancies using an overnight-stored pancreatic juice cell block specimen.

BACKGROUND AND AIMS: Pancreatic juice cytology is useful for diagnosing pancreatic duct strictures and cystic lesions. However, some cases cannot be diagnosed using cytology. This study aimed to evaluate the utility of the overnight-stored pancreatic juice cell block (CB) method for diagnosing pancreatic disease. METHODS: This retrospective study included 32 patients who presented with pancreatic duct strictures or cystic lesions between 2018 and 2024. The sensitivity, specificity, and accuracy of the CB method and single/multiple pancreatic juice cytology were compared to evaluate the utility of the CB. RESULT: An endoscopic nasopancreatic drainage tube was placed in the main pancreatic duct, and pancreatic juice was collected to create a CB specimen. The median amount of pancreatic juice collected was 180(30-200) mL, and the median number of cytological examinations was three(2-8). Of the 32 cases, 13 were malignant, and 19 were benign (non-malignant). The sensitivity was significantly higher for the CB method (62 %) than for single cytology(15 %, P = 0.0414), and there was no significant difference between CB and multiple cytology(54 %, P = 1.0). The specificity and accuracy were not significantly different between the CB method and single or multiple cytology. When multiple cytology and CB were combined, sensitivity improved to 77 %. The pathological findings of the CB specimens were similar to the surgical specimens, including immunohistochemistry. CONCLUSION: The overnight-stored pancreatic juice CB method was more effective than single cytology, with similar sensitivities to multiple cytology and can also be used for immunohistochemistry. The pancreatic juice CB method is useful for pancreatic juice assessment.

[Modern endoscopic technologies for chronic calcifying pancreatitis]. / Sovremennye endoskopicheskie tekhnologii pri khronicheskom kal'tsinoznom pankreatite.

OBJECTIVE: To evaluate the effectiveness and safety of electrohydraulic lithotripsy of calculi of the main pancreatic duct using ultrathin SpyGlass DS endoscope. MATERIAL AND METHODS: The study included 29 patients with chronic calcifying pancreatitis and obstructive calculi of the main pancreatic duct. All surgeries were carried out between 2018 and 2023. RESULTS: Complete removal of calculi (≥5 mm) within one procedure was achieved in 25 (86%) patients. CONCLUSION: Pancreatoscopy with electrohydraulic lithotripsy using the digital SpyGlass DS system (BostonScientificCorp, Marlborough, MA) is the most effective method for calculi of the main pancreatic duct.

[Intraductal radiofrequency ablation for neoplasms of the major duodenal papilla with intraductal spread]. / Vnutriprotokovaya radiochastotnaya ablyatsiya pri novoobrazovaniyakh bol'shogo sosochka dvenadtsatiperstnoi kishki s vnutriprotokovym rasprostraneniem.

OBJECTIVE: To analyze the efficacy of intraductal radiofrequency ablation (RFA) for neoplasms of the major duodenal papilla with intraductal spread. MATERIAL AND METHODS: Eleven patients with adenomas of the major duodenal papilla and intraductal spread underwent intraductal RFA between 2022 and 2023. Spread to the common bile duct ranged from 10 to 30 mm, to the main pancreatic duct - from 5 to 11 mm. RESULTS: Technical success was achieved in all cases. Complications after intraductal RFA occurred in 4 cases (post-manipulation pancreatitis - 2 cases, repeated intraductal RFA for residual adenomatous growths - 2 cases). Technical success of stenting of the main pancreatic and common bile ducts was achieved in all cases. CONCLUSION: Intraductal radiofrequency ablation for neoplasms of the major duodenal papilla with intraductal spread ensured complete destruction of intraductal tumor with adequate clinical effect and no need for highly traumatic surgery.

Clinical Relevance of Cancerization of Ducts in Resected Pancreatic Ductal Adenocarcinoma.

OBJECTIVES: Although prevalent in 50%-90% of pancreatic ductal adenocarcinomas, the clinical relevance of "cancerization of ducts" (COD) remains unknown. METHODS: Pathologists retrospectively reviewed slides classifying prevalence of COD. Histopathological parameters, location of first recurrence, recurrence-free survival (RFS), and overall survival (OS) were collected from the institutional pancreatectomy registry. RESULTS: Among 311 pancreatic ductal adenocarcinomas, COD was present in 216 (69.5%) and more prevalent in the cohort that underwent upfront surgery (75.3% vs 63.1%, P = 0.019). Furthermore, COD was associated with female gender (P = 0.040), advanced T stage (P = 0.007), perineural invasion (P = 0.014), lymphovascular invasion (P = 0.025), and R1 margin (P = 0.009), but not N stage (P = 0.401) or tumor differentiation (P = 0.717). In multivariable regression, COD was associated with less liver recurrence (odds ratio, 0.44; P < 0.005). This association was driven by the cohort of patients who had received preoperative treatment (odds ratio, 0.18; P < 0.001). COD was not predictive for RFS or OS. CONCLUSIONS: Cancerization of ducts was not associated with RFS or OS. Currently underrecognized, standardized implementation into histopathological reports may have merit, and further mechanistic scientific experiments need to illuminate its clinical and biologic impact.

Impact of pancreatic ductal occlusion on postoperative outcomes in pancreatic head cancer patients undergoing neoadjuvant therapy.

BACKGROUND: Pancreatic ductal occlusion can accompany pancreatic head cancer, leading to pancreatic exocrine insufficiency (PEI) and adverse effects on nutritional status and postoperative outcomes. We investigated its impact on nutritional status, body composition, and postoperative outcomes in patients with pancreatic head cancer undergoing neoadjuvant therapy (NAT). METHODS: We analyzed 136 patients with pancreatic head cancer who underwent NAT prior to intended pancreaticoduodenectomy (PD) between 2015 and 2022. Nutritional and anthropometric indices (body mass index [BMI], albumin, prognostic nutritional index [PNI], Glasgow prognostic score, psoas muscle index, subcutaneous adipose tissue index [SATI], and visceral adipose tissue index) and postoperative outcomes were compared between the occlusion (n = 78) and non-occlusion (n = 58) groups, in which 61 and 44 patients, respectively, ultimately underwent PD. RESULTS: The occlusion group showed significantly lower post-NAT BMI, PNI, and SATI (p = 0.011, 0.005, and 0.015, respectively) in the PD cohort. The occlusion group showed significantly larger main pancreatic duct, smaller pancreatic parenchyma, and greater duct-parenchymal ratio (p < 0.001), and these morphological parameters significantly correlating with post-NAT nutritional and anthropometric indices. Postoperative 3-year survival and recurrence-free survival (RFS) rates were significantly poorer (p = 0.004 and 0.013) with pancreatic ductal occlusion, also identified as an independent postoperative risk factor for overall survival (hazard ratio [HR]: 2.31, 95% confidence interval [CI] 1.08-4.94, p = 0.030) and RFS (HR: 2.03, 95% CI 1.10-3.72, p = 0.023), in multivariate analysis. CONCLUSIONS: Pancreatic ductal occlusion may be linked to poorer postoperative outcomes due to PEI-related malnutrition.

Utility of Contrast-Enhanced Harmonic Endoscopic Ultrasonography to Diagnose Pancreaticobiliary Maljunction.

BACKGROUND: Detection of a common channel outside the duodenal wall is important in diagnosing pancreaticobiliary maljunction (PBM). The present study evaluated the utility of contrast-enhanced harmonic endoscopic ultrasonography (CH-EUS) in diagnosing PBM. METHODS: This single-center retrospective study enrolled 45 patients who were diagnosed with PBM or high confluence of pancreatobiliary ducts (HCPBD) between January 2007 and December 2021. The diagnostic sensitivities of contrast-enhanced computed tomography (CE-CT), magnetic resonance imaging (MRI), and CH-EUS for diagnosing PBM were analyzed. Imaging findings were evaluated by two reviewers blinded to the clinicopathological results. RESULTS: Based on diagnostic criteria, 33 patients were diagnosed with PBM and 12 with HCPBD. Compared with the patients with HCPBD, those with PBM had significantly longer common channel (12.5 mm vs. 8.1 mm, P = 0.018) and common bile duct (13.0 mm vs. 8.6 mm, P = 0.049) lengths. The κ-coefficients for differentiating PBM and HCPBD were 0.871 between CE-CT and MRI, 0.330 between CE-CT and CH-EUS, and 0.611 between MRI and CH-EUS. The diagnostic sensitivity of CH-EUS (95.2%) was higher than that of CE-CT (83.3%) and MRI (82.8%), although the differences were not statistically significant. CONCLUSION: CH-EUS may be useful for the diagnosis of PBM.