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.

Heavy metals in cigarette smoke strongly inhibit pancreatic ductal function and promote development of chronic pancreatitis.

BACKGROUND AND AIMS: Smoking is recognised as an independent risk factor in the development of chronic pancreatitis (CP). Cystic fibrosis transmembrane conductance regulator (CFTR) function and ductal fluid and bicarbonate secretion are also known to be impaired in CP, so it is crucial to understand the relationships between smoking, pancreatic ductal function and the development of CP. METHODS: We measured sweat chloride (Cl-) concentrations in patients with and without CP, both smokers and non-smokers, to assess CFTR activity. Serum heavy metal levels and tissue cadmium concentrations were determined by mass spectrometry in smoking and non-smoking patients. Guinea pigs were exposed to cigarette smoke, and cigarette smoke extract (CSE) was prepared to characterise its effects on pancreatic HCO3 - and fluid secretion and CFTR function. We administered cerulein to both the smoking and non-smoking groups of mice to induce pancreatitis. RESULTS: Sweat samples from smokers, both with and without CP, exhibited elevated Cl- concentrations compared to those from non-smokers, indicating a decrease in CFTR activity due to smoking. Pancreatic tissues from smokers, regardless of CP status, displayed lower CFTR expression than those from non-smokers. Serum levels of cadmium and mercury, as well as pancreatic tissue cadmium, were increased in smokers. Smoking, CSE, cadmium, mercury and nicotine all hindered fluid and HCO3 - secretion and CFTR activity in pancreatic ductal cells. These effects were mediated by sustained increases in intracellular calcium ([Ca2+]i), depletion of intracellular ATP (ATPi) and mitochondrial membrane depolarisation. CONCLUSION: Smoking impairs pancreatic ductal function and contributes to the development of CP. Heavy metals, notably cadmium, play a significant role in the harmful effects of smoking. KEY POINTS: Smoking and cigarette smoke extract diminish pancreatic ductal fluid and HCO3 - secretion as well as the expression and function of CFTR Cd and Hg concentrations are significantly higher in the serum samples of smokers Cd accumulates in the pancreatic tissue of smokers.

[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.

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.

Endoscopic ultrasound-guided versus surgical pancreatic duct drainage after failed endoscopic retrograde pancreatography: a pilot comparative study.

BACKGROUND: Endoscopic ultrasound-guided pancreatic duct (PD) drainage (EUS-PDD) is being increasingly performed as an alternative method to surgical drainage to achieve PD decompression after failed endoscopic retrograde pancreatography (ERP). However, no directly study has compared EUS-PDD with surgical PD drainage after failed ERP in patients with chronic pancreatitis. METHODS: Consecutive patients who underwent EUS-PDD or longitudinal pancreaticojejunostomy after failed ERP were retrospectively identified from our endoscopy and medical information systems. The primary end point was the Izbicki pain score. The secondary end points were pain relief at the end of follow-up, procedure outcomes, adverse events, readmission, and reintervention. RESULTS: A total of 21 patients (11 EUS-PDD, 10 surgical drainages) were analyzed. There were no significant differences in mean Izbicki pain score (EUS-PDD, 13.6 ± 10.1 vs. surgical drainage 10.7 ± 7.9, p = 0.483) or complete/partial pain relief (60%/30% vs. 70%/30%, p = 0.752) at the end of follow-up of the two groups. The rates of overall adverse events (27.3% vs. 30.0%, p = 0.893) and readmission (63.6% vs. 40.0%, p = 0.290) were similar in the two treatment groups, while patients in EUS-PDD group required more reinterventions (45.5% vs. 0%, p = 0.039) compared with patients in the surgery group. CONCLUSION: EUS-PDD showed comparable pain relief and safety to surgical PD drainage after failed ERP, with a higher rate of reintervention. The selection of EUS-PDD or surgical drainage may be appropriate based on an individualized strategy.

[Study on the application of self-fixing and self-detachable drainage stent in pancreaticojejunostomy].

Objectives: To evaluate the efficacy and safety of the self-fixing and self-detachable drainage stent in pancreaticojejunostomy and to provide supportive data for the follow clinical trials. Methods: This is an experimental research in animals which completed from February 2022 to September 2022. A self-fixing and self-detachable pancreaticojejunostomy drainage stent was designed for Hong's pancreaticojejunostomy technique based on the theory of "fistula healing" in pancreaticojejunostomy. Ten biocompatibility tests were completed in vitro before this study. Twenty-five Bama minipigs were selected and double-ligated in the neck of the pancreas to dilate the distal main pancreatic duct. Twenty-three of them were successfully modelled and divided into three groups by a stratified random method: pancreaticojejunostomy drainage stent group (referred to as stent group) with 11 pigs, pancreatic duct to jejunal mucosa anastomosis group (referred to as manual suture group) with 8 pigs, sham operation group with 4 pigs. The anastomic time,amylase content in postoperative abdominal drainage fluid and the tolerable pressure value of pancreaticojejunostomy were compared between the stent group and the manual suture group. An abdominal X-ray fluoroscopy examination was adopted to detect the detach time of the stent. A postoperative pathological examination was performed to verify the healing time,the type of treatment and the stricture rate of pancreaticojejunostomy. Quantitative data was analyzed by independent sample t-test. The classified data were analyzed by Fisher's exact test. Results: There were no significant differences in the diameter of the pancreatic duct and pancreatic texture,the time of pancreaticojejunostomy,the amylase content in postoperative peritoneal drainage fluid,and the tolerable pressure value of the pancreaticojejunostomy between the stent group and the manual suture group(all P>0.05). Abdominal X-ray fluoroscopy showed that the stents gradually detached and were removed from the body 21 days after operation,and all stents were detached in the follow 3 months after operation. Pancreaticojejunostomy healed 7 days after operation based on fistula formation in the stent group,and 14 days in the manual suture group. The incidence of anastomotic stricture within 35 days after operation was 2/8 in the stent group and 6/8 in the manual suture group (Fisher's exact test: P=0.132). Conclusion: The stent method is safer and simpler than the manual suture method in pancreaticojejunostomy of Bama minipigs, with shorter anastomotic healing time and lower stricture rate.

A case of spontaneous acute obstructive suppurative pancreatic ductitis associated with intraductal papillary mucinous neoplasms.

A 77-year-old woman was referred to our hospital due to left upper abdominal pain, appetite loss and body weight loss for 1 month. Her past medical history was diabetes and intraductal papillary mucinous neoplasms (IPMNs). She had no fever and physical examination revealed mild tenderness in the left upper abdomen. Blood tests showed elevated inflammatory response with normal serum pancreatic enzymes. Contrast-enhanced CT showed marked swelling of the pancreatic tail, increased peripancreatic fatty tissue density, multiple IPMNs and obscuration of the enlarged main pancreatic duct at the tail. EUS showed there was no obvious mass in the pancreas and protein plug was suspected in the main pancreatic duct. EUS-FNA was performed and pathology showed no malignancy. ERCP showed discharge of purulent pancreatic fluid from the major duodenal papilla and stenosis of the main pancreatic duct at the tail. The culture of the purulent pancreatic fluid revealed Streptococcus aureus, Klebsiella pneumoniae and Pseudomonas aeruginosa, leading to diagnosis of acute obstructive suppurative pancreatic ductitis (AOSPD). Endoscopic nasopancreatic drainage and antimicrobial treatment were started. The inflammatory response improved rapidly and the patient was discharged 30 days after admission. To our knowledge, this is the second reported case of spontaneous AOSPD associated with IPMNs.