Differentiating localized autoimmune pancreatitis and pancreatic ductal adenocarcinoma using endoscopic ultrasound images with deep learning.

Objectives: Localized autoimmune pancreatitis is difficult to differentiate from pancreatic ductal adenocarcinoma on endoscopic ultrasound images. In recent years, deep learning methods have improved the diagnosis of diseases. Hence, we developed a special cross-validation framework to search for effective methodologies of deep learning in distinguishing autoimmune pancreatitis from pancreatic ductal adenocarcinoma on endoscopic ultrasound images. Methods: Data from 24 patients diagnosed with localized autoimmune pancreatitis (8751 images) and 61 patients diagnosed with pancreatic ductal adenocarcinoma (20,584 images) were collected from 2016 to 2022. We applied transfer learning to a convolutional neural network called ResNet152, together with our innovative imaging method contributing to data augmentation and temporal data process. We divided patients into five groups according to different factors for 5-fold cross-validation, where the ordered and balanced datasets were created for the performance evaluations. Results: ResNet152 surpassed the endoscopists in all evaluation metrics with almost all datasets. Interestingly, when the dataset is balanced according to the factor of the endoscopists' diagnostic accuracy, the area under the receiver operating characteristic curve and accuracy were highest at 0.85 and 0.80, respectively. Conclusions: It is deduced that image features useful for ResNet152 correlate with those used by endoscopists for their diagnoses. This finding may contribute to sample-efficient dataset preparation to train convolutional neural networks for endoscopic ultrasonography-imaging diagnosis.

Associations between subjective well-being, number of teeth, and self-rated mastication in Japanese adults: A cross-sectional study.

This cross-sectional study aimed to investigate the risk factors for low levels of subjective well-being (SWB) in the general population of Japan, specifically, the impact of the number of teeth and self-rated mastication. The surveyed population consisted of individuals aged between 40 and 79 years from Yamagata prefecture, Japan. A postal self-administered questionnaire survey of respondents lifestyles, medical history, oral health, and dietary intake, was conducted from 2017 to 2021. We included 6846 participants to confirm the independent associations between SWB and several parameters using multivariate ordinal logistic regression analysis to estimate adjusted odds ratios and 95% confidence intervals. Individuals with < 20 teeth and poor mastication ability had a 1.3-fold risk for low levels of SWB compared with individuals with ≥ 20 teeth with good mastication ability (adjusted odds ratios = 1.300, 95% confidence intervals = 1.043-1.621, P = .020). There were no differences between individuals with good mastication ability, regardless of the number of remaining teeth. Our study emphasizes not only the importance of having ≥ 20 teeth and good mastication ability for high levels of SWB but also the importance of restoring mastication ability using some form of prosthesis, to facilitate a high level of SWB when the number of remaining teeth is < 20.

Association of health behaviors, dietary habits, and oral health with weight gain after 20 years of age in community-dwelling Japanese individuals aged 40 years and older: a cross-sectional study.

OBJECTIVES: This cross-sectional study investigated the factors associated with weight gain ≥ 10 kg after 20 years of age in the general Japanese population, with a focus on the number of teeth. MATERIALS AND METHODS: We included individuals aged ≥ 40 years from Yamagata prefecture, Japan from 2017-2021. A postal survey was conducted using a self-administered questionnaire; 5,940 participants were included in the final analysis. The questionnaire included items on lifestyle factors, medical history, physical and mental conditions, oral health, and dietary intake. A multivariate logistic regression analysis was used to identify independent associations between weight gain ≥ 10 kg after 20 years of age and various parameters; adjusted odds ratios (ORs) and 95% confidence intervals (CIs) were estimated. RESULTS: Less than 20 teeth, male sex, drinking habit frequency, eating very fast or fast, and a higher frequency of eating-away-from-home were significant factors associated with weight gain ≥ 10 kg after 20 years of age; individuals with < 20 versus > 20 teeth exhibited a 1.35-fold higher OR (95% CI 1.15-1.59; p < 0.01). CONCLUSIONS: Our results suggest that having < 20 teeth may affect weight gain ≥ 10 kg after 20 years of age. However, owing to the cross-sectional study design, causality could not be determined. Therefore, maintaining healthy lifestyle behaviors to avoid tooth loss may also affect weight gain ≥ 10 kg after 20 years of age. CLINICAL RELEVANCE: Having < 20 teeth has the potential to affect long-term weight gain after 20 years of age.

Role of Bile-Derived Extracellular Vesicles in Hepatocellular Proliferation after Partial Hepatectomy in Rats.

Although liver regeneration has been extensively studied, the effects of bile-derived extracellular vesicles (bile EVs) on hepatocytes has not been elucidated. We examined the influence of bile EVs, collected from a rat model of 70% partial hepatectomy (PH), on hepatocytes. We produced bile-duct-cannulated rats. Bile was collected over time through an extracorporeal bile duct cannulation tube. Bile EVs were extracted via size exclusion chromatography. The number of EVs released into the bile per liver weight 12 h after PH significantly increased. Bile EVs collected 12 and 24 h post-PH, and after sham surgery (PH12-EVs, PH24-EVs, sham-EVs) were added to the rat hepatocyte cell line, and 24 h later, RNA was extracted and transcriptome analysis performed. The analysis revealed that more upregulated/downregulated genes were observed in the group with PH24-EVs. Moreover, the gene ontology (GO) analysis focusing on the cell cycle revealed an upregulation of 28 types of genes in the PH-24 group, including genes that promote cell cycle progression, compared to the sham group. PH24-EVs induced hepatocyte proliferation in a dose-dependent manner in vitro, whereas sham-Evs showed no significant difference compared to the controls. This study revealed that post-PH bile Evs promote the proliferation of the hepatocytes, and genes promoting cell cycles are upregulated in hepatocytes.

Association of the number of teeth and self-rated mastication with self-rated health in community-dwelling Japanese aged 40 years and older: the Yamagata cohort study.

Self-rated health (SRH) is a predictive factor for health-related prognoses such as mortality. This study aimed to comprehensively investigate the risk factors for poor SRH in the general population of Japan, focusing on the combination of the number of teeth and self-rated mastication. Individuals aged at least 40 years in Yamagata Prefecture, Japan, were surveyed from 2017 to 2021. The participants answered a self-administered postal survey on lifestyle factors, medical history, physical and mental conditions, oral health, and dietary intake, and 6739 participants were included. Multivariate logistic regression analysis showed that individuals with less than 20 teeth and who bite tightly on one side or neither side were at a 1.422- and 1.952-fold significantly higher risk, respectively, of poor SRH than individuals with at least 20 teeth and who bite tightly on both sides. Moreover, individuals who had less than 20 teeth but could bite tightly on both sides did not have a significant risk compared to those who had at least 20 teeth and could bite tightly on both sides. Regarding individuals with more than 20 teeth, there was no difference between those who could and could not bite tightly on both sides, although the odds ratios for poor SRH tended to increase for those who could bite on one side or neither side. Our results emphasize the importance of having at least 20 teeth without periodontal disease and oral rehabilitation using a type of prosthesis for SRH, even with less than 20 teeth.

A Cross-Sectional Survey on the Association between Dental Health Conditions and University Personality Inventory Scores among University Students: A Single-Center Study in Japan.

This study examined the association between dental health conditions and scores on the University Personality Inventory (UPI) among university students in Japan. Participants were freshmen at Yamagata University between 2010 and 2019. Dental check-ups, including dental caries, periodontal disease, malocclusion, and temporomandibular disorders (TMD), and mental health screening using the UPI were performed; 12,433 students were included in the final analysis. A logistic regression analysis was performed to confirm the association between dental health conditions and >30 UPI scores, which indicate the need to consult mental health professionals. Overall, students who required treatment for TMD had a 3.165-fold higher risk of >30 UPI scores (OR = 3.165, 95% CI = 1.710−5.857). Periodontal disease and TMD in male participants (periodontal disease: OR = 1.329, 95% CI = 1.108−1.595; TMD: OR = 3.014, 95% CI = 1.107−8.204) and TMD in female participants (OR = 2.938, 95% CI = 1.340−6.445) were significant risk factors for >30 UPI scores. Students requiring treatment for TMD were at risk of obtaining >30 UPI scores. Although our study has several limitations, students with subjective symptoms (e.g., disturbance in opening the mouth) should take the UPI test or in some cases consult mental health professionals.

A case of successful removal of a migrated fish bone in the bile duct after pancreaticoduodenectomy using overtube-assisted cholangioscopy.

Fish bone migration into the bile duct in patients with surgically altered anatomy is a very rare cause of bile duct stones. Recently, balloon-assisted endoscopic retrograde cholangiopancreatography (BAERCP) is performed for biliary lesions in patients with surgically altered anatomy. We report on a 73-year-old Japanese man with a history of pancreaticoduodenectomy for intraductal papillary mucinous adenoma. A 20 mm long linear hyperattenuating structure in the left intrahepatic bile duct was noted on routine follow-up computed tomography 14 years postoperatively. The linear structure persisted until follow-up computed tomography performed 15 years postoperatively, and the left intrahepatic bile duct was shown to be dilated. We performed BAERCP for the diagnosis and treatment of the linear structure but could not visualize the linear structure in the left intrahepatic bile duct via enteroscopy and fluoroscopy. We removed the enteroscope, leaving the overtube, and inserted the cholangioscope through the overtube over the guide wire. We observed a brown rod-shaped linear structure in the left intrahepatic bile duct and removed it under direct visualization via overtube-assisted cholangioscopy. We conclude that overtube-assisted cholangioscopy was useful for assessing undiagnosed biliary lesions using conventional BAERCP and removing fish bones in the bile duct of the patient with altered gastrointestinal anatomy.

Biosafety of a novel covered self-expandable metal stent coated with poly(2-methoxyethyl acrylate) in vivo.

Covered self-expandable metal stents (CSEMS) are often used for palliative endoscopic biliary drainage; however, the unobstructed period is limited because of sludge occlusion. The present study aimed to evaluate the biosafety of a novel poly(2-methoxyethyl acrylate)-coated CSEMS (PMEA-CSEMS) for sludge resistance and examine its biosafety in vivo. Using endoscopic retrograde cholangiopancreatography, we placed the PMEA-CSEMS into six normal porcine bile ducts and conventional CSEMS into three normal porcine bile ducts. We performed serological examination and undecalcified histological analysis at 1, 3, and 6 months during follow-up. In the bile ducts with PMEA-CSEMS or conventional CSEMS, we observed no increase in liver enzyme or inflammatory marker levels in the serological investigations and mild fibrosis but no inflammatory response in the histopathological analyses. Thus, we demonstrated the biosafety of PMEA-CSEMS in vivo.

Pathways for the development of multiple epithelial types of intraductal papillary mucinous neoplasm of the pancreas.

BACKGROUND: Intraductal papillary mucinous neoplasm (IPMN) of the pancreas is categorized into four distinct types: the gastric, intestinal, pancreatobiliary, and oncocytic. Each type is associated with specific clinicopathological features. We aimed to uncover the molecular mechanisms underlying the development of these types of IPMN. METHODS: We obtained 103 lesions of various types, including 49 gastric, 26 intestinal, 22 pancreatobiliary, and 6 oncocytic lesions, from 43 IPMNs, including 36 with multiple types. Comparative analysis was performed by targeted sequencing of 37 genes in different lesion types within each pancreas. RESULTS: Gastric-type low-grade lesions were observed in all 36 tumors with multiple types, with 245 mutations identified across all samples. The average number of mutations was significantly different between different lesion grades and types: 1.88 for low-grade lesions, 2.77 for high-grade lesions, and 2.38 for invasive lesions (p = 0.0067); and 1.96 for gastric-type lesion, 2.92 for intestinal-type lesion, 2.73 for pancreatobiliary-type lesion, and 2.17 for oncocytic-type lesion (p = 0.0163). Tracing of mutations between lesions containing multiple types in the same pancreas suggested three developmental pathways, denoted as "progressive", "divergent", and "independent". The progressive and divergent pathways indicate an ancestral lesion that was mostly gastric-type and low-grade may progress or diversify into lesions of other types and/or higher grades. The independent pathway suggests that some high-grade lesions of any type may develop independently. CONCLUSION: These findings suggest that gastric-type low-grade lesions have a risk of progression into high-grade lesions of other types. Therefore, low-grade gastric-type IPMNs should be under constant surveillance.

A fully covered self-expandable metallic stent coated with poly (2-methoxyethyl acrylate) and its derivative: In vitro evaluation of early-stage biliary sludge formation inhibition.

The adhesion and deformation behavior of proteins at the inner surface of fully covered, self-expandable metallic stents coated with biocompatible polymers, poly(2-methoxyethyl acrylate) (PMEA) and poly(3-methoxypropyl acrylate) (PMC3A), were analyzed. Model bile solution, proteins, and bacteria were used to unravel the inhibitory ability of the polymer coatings. Adsorbance of proteins and adherence of bacteria were both strongly inhibited by the polymer coatings. Circulation tests were performed under clinical conditions using human bile from patients. Adsorption/deformation of proteins and early-stage sludge formation were inhibited on stent surfaces coated with PMEA derivatives. The present study revealed that early-stage biliary sludge formation on PMEA- and PMC3A-coated stents was suppressed due to the strong resistance of the polymers to protein adsorption/deformation, brought about by intermediate water in hydrated polymer coatings, which is not present in conventional coating materials, such as silicone and polyurethane.

Utility of Claudin-3 in extracellular vesicles from human bile as biomarkers of cholangiocarcinoma.

Extracellular vesicles (EVs) are released from all cells. Bile directly contacts bile duct tumor; bile-derived EVs may contain high concentrations of cancer biomarkers. We performed a proteomic analysis of human bile-derived EVs and identified a novel biomarker of cholangiocarcinoma (CCA). EVs were isolated using ultracentrifugation, and chelating agents, ethylenediaminetetraacetic acid and ethylene glycol tetraacetic acid (EDEG) and phosphate buffered saline (PBS) were used as dissolution solutions. Bile was collected from 10 CCA and 10 choledocholithiasis (stones) cases. Proteomic analysis was performed; subsequently, ELISA was performed using the candidate biomarkers in a verification cohort. The vesicles isolated from bile had a typical size and morphology. The expression of exosome markers was observed. RNA was more abundant in the EDEG group. The proportion of microRNA was higher in the EDEG group. EDEG use resulted in the removal of more contaminants. Proteomic analysis identified 166 proteins as CCA-specific. ELISA for Claudin-3 revealed statistically significant difference. The diagnostic accuracy was AUC 0.945 and sensitivity and specificity were 87.5%. We report the first use of EDEG in the isolation of EVs from human bile and the proteomic analysis of human bile-derived EV-proteins in CCA. Claudin-3 in bile-derived EVs is a useful biomarker for CCA.

A case of a smooth transition to subsequent percutaneous transjejunal biliary intervention for hepatolithiasis after biliary reconstruction by adding jejunostomy during an emergency operation for perforation due to balloon-assisted endoscopy.

Treatments for hepatolithiasis include peroral endoscopy, percutaneous cholangioscopy, and surgery. Balloon-assisted endoscopic retrograde cholangiopancreatography (BAERCP) has been widely performed in recent years for patients with hepatolithiasis after biliary reconstruction. However, accidental bowel perforation caused by BAERCP may need emergency surgery. Here, we describe a 77-year-old Japanese woman diagnosed with acute cholangitis due to hepatolithiasis after biliary reconstruction (a biliary diversion operation for pancreaticobiliary maljunction). She underwent BAERCP for treatment of hepatolithiasis, however, a small-bowel perforation occurred. She underwent an emergency operation to suture the perforation and add a catheter jejunostomy. She had no postoperative complications after surgery and was discharged 11 days after surgery. One month later, she was readmitted and underwent percutaneous transjejunal cholangioscopy-guided lithotripsy with complete removal of the calculi. Although endoscopists should be careful to avoid small-bowel perforation during BAERCP, if perforation occurs, addition of a catheter jejunostomy during emergency surgery can be easily transitioned to subsequent treatment of the hepatolithiasis.

Pancreatic perfusion imaging method that reduces radiation dose and maintains image quality by combining volumetric perfusion CT with multiphasic contrast enhanced-CT.

OBJECTIVES: The aim of this study is to propose and evaluate a new method of volumetric perfusion computed tomography (PCT) incorporated into pancreatic multiphasic contrast enhanced (CE)-CT in the clinical setting. METHODS: In this ethically approved study, PCT was incorporated into our existing scanning protocol in 17 patients and effective doses related to PCT were evaluated. CT values and signal-to-noise ratio (SNR) of anatomical structure were compared in diagnostic images that were acquired using 320-detector volumetric scan mode and 64-detector helical scan mode. In addition, focal lesion depiction was qualitatively assessed in the two groups. Perfusion parameters in normal pancreas were measured by two radiologists and the interobserver-reliability was assessed. RESULTS: The effective dose of PCT was 5.1 ± 0.3 mSv. The actual effective dose (AED) including the dose used in volumetric scans for diagnostic imaging was 22.8 ± 5.3 mSv and the putative effective dose (PED) was 21.9 ± 9.1 mSv on average. There was no significant difference between AED and PED (p = 0.404). Compared with conventional helical scans, volumetric scans did not decrease CT values or SNR, but rather significantly increased those of the aorta in the arterial phase. Both groups had acceptable qualitatively assessed image quality with no significant difference in the depiction of each structure. There was almost perfect interobserver agreement in the measurement of perfusion parameters (mean ICCs > 0.9). CONCLUSIONS: Our scanning protocol for pancreatic perfusion CT provides high-quality images while requiring lower radiation doses than conventional methods.

How does intestinal-type intraductal papillary mucinous neoplasm emerge? CDX2 plays a critical role in the process of intestinal differentiation and progression.

Intestinal-type intraductal papillary mucinous neoplasm (IPMN) of the pancreas is clinicopathologically distinctive. Our research aimed to elucidate the molecular mechanism of the development and progression of the intestinal-type IPMN. In 60 intestinal-type IPMN specimens, histological transitions from gastric-type epithelia to intestinal-type epithelia were observed in 48 cases (80%). CDX2/MUC2/alcian blue triple staining indicated that CDX2 appeared to precede MUC2 expression and subsequent alcian blue-positive mucin production. Expression of p21 and Ki-67 seemed to be accelerated by CDX2 expression (p = 6.02e-13 and p = 3.1e-09, respectively). p21/Ki-67 double staining revealed that p21 was mostly expressed in differentiated cells in the apex of papillae, while Ki-67 was expressed in proliferative cells in the base of papillae. This clear cellular arrangement seemed to break down with the progression of atypical grade and development of invasion (p = 0.00197). Intestinal-type IPMNs harbored frequent GNAS mutations (100%, 25/25) and RNF43 mutations (57%, 8/14) and shared identical GNAS and KRAS mutations with concurrent gastric-type IPMNs or incipient gastric-type neoplasia (100%, 25/25). RNF43 mutations showed emerging or being selected in intestinal-type neoplasms along with ß-catenin aberration. Activation of protein kinase A and extracellular-regulated kinase was observed in CDX2-positive intestinal-type neoplasm. These results suggest that gastric-type epithelia that acquire GNAS mutations together with induction of intrinsic CDX2 expression may evolve with clonal selection and additional molecular aberrations including RNF43 and ß-catenin into intestinal-type IPMNs, which may further progress with complex villous growth due to disoriented cell cycle regulation, acceleration of atypical grade, and advance to show an invasive phenotype.

Usefulness of rapid on-site evaluation specimens from endoscopic ultrasound-guided fine-needle aspiration for cancer gene panel testing: A retrospective study.

Pancreatic cancer (PC) is a highly lethal malignancy, with a 5-year survival rate of 6%. Cancer gene panel testing is expected to allow selection of suitable therapeutic drugs in individual patients with PC and improve their prognosis. Although somatic mutations can be identified in formalin-fixed, paraffin-embedded samples derived from surgical specimen, the rate of surgical indication among patients with PC is only 20%. To acquire genome information with a less invasive method, we used rapid on-site evaluation (ROSE) specimens from endoscopic ultrasound-guided fine-needle aspiration. The present study aimed to retrospectively evaluate the utility of comprehensive cancer gene panel testing with ROSE specimens. DNA was extracted from preserved ROSE specimens of 26 patients diagnosed with PC between 2011 and 2017. DNA sequences of oncogenes and cancer-related genes were determined using the Ion AmpliSeq Comprehensive Caner Panel. We compared KRAS mutations between cancer gene panel testing by next-generation sequencing (NGS) and KRAS mutation analysis by polymerase chain reaction. The mean yield of DNA per extraction from ROSE specimens was 171 ng (range, 34-478 ng). On cancer gene panel testing, we noted KRAS mutations (92%), TP53 mutations (50%), CDKN2A mutations (15%), and SMAD4 mutations (31%). The concordance rate of KRAS mutations between cancer gene panel testing by NGS using ROSE specimens and KRAS mutation analysis by the companion diagnostics using residual materials was 81%. Among five cases of KRAS discordance, three showed KRAS mutations in cancer gene panel testing but not in KRAS mutation analysis. Cancer gene panel testing with ROSE specimens can help stratify unresectable PC patients without additional invasive approaches, and it can be used for therapeutic drug selection.

Signet-ring cell carcinoma of the ampulla of Vater: a case diagnosed via repeated biopsies.

Signet-ring cell carcinoma of the ampulla of Vater is a rare tumor. A 74-year-old woman presented with epigastric pain and was diagnosed with cholangitis. Her liver enzyme levels were elevated. Computed tomography showed an enhanced area in the periampullary region and marked common bile duct dilatation. On endoscopic retrograde cholangiopancreatography (ERCP), the ampulla exhibited a normal appearance without ulcer or mass. Histological biopsy confirmed the absence of malignancy. During follow-up, the patient again presented with acute cholangitis multiple times and underwent ERCP each time. The ampulla had the appearance of a reddish and erosive mucosa. Although biopsy was repeated, histological examination did not show any malignancy. After a total of 13 biopsies, the patient was diagnosed with ampullary carcinoma of non-exposed protruded type following the third ERC-guided biopsy. Careful follow-up and frequent endoscopic biopsies are important in cases of papillary carcinoma of non-exposed protruded type with normal ampullary mucosa on initial endoscopy because this condition is challenging to diagnose with a single biopsy.

A novel pathogenic variant of ATP-binding cassette subfamily B member 4 causing gallstones in a young adult.

The low phospholipid-associated cholelithiasis (LPAC) syndrome was reported in European adults with cholelithiasis and a mutation of the ATP-binding cassette subfamily B member 4 (ABCB4). The ABCB4 encodes multidrug resistance 3, which is a phospholipid translocator. Reduced phospholipid transport can lead to the formation of biliary cholesterol stones. Here, we describe a 31-year-old Japanese man diagnosed with recurrent biliary colic. Although he recovered quickly after endoscopic treatment for the most recent presentation, he had a family history of similar problems. His mother had required endoscopic treatment for choledocholithiasis and his maternal aunt had died at age 29 years because of liver failure (etiology unknown). We, therefore, performed genetic analysis, which revealed a heterozygous ABCB4C717S. LPAC syndrome was diagnosed and the patient has received ursodeoxycholic acid for 2 years with no recurrence. The same variant was identified in the patient's mother, who was subsequently found to have a left intrahepatic calculus requiring left-sided lobectomy. She has received ursodeoxycholic acid for 1 year with no recurrence. ABCB4C717S is a novel pathogenic variant, and this is the first patient diagnosed with LPAC syndrome in Japan. We should consider LPAC syndrome in young adults with recurrent cholesterol gallstones to ensure early therapy.

[Hypopituitarism associated with autoimmune pancreatitis: a case report].

We herein report the case of a 64-year-old male patient with hypopituitarism associated with autoimmune pancreatitis (AIP). The patient was previously diagnosed with AIP based on the presence of a swollen pancreas, elevated serum immunoglobulin G4, and narrowing of the pancreatic duct by imaging. Magnetic resonance imaging revealed a pituitary stem tumor, and loading test showed a decrease in the function of the anterior lobe suggesting severe failure of growth hormone secretion. Treatment with steroids was effective in reducing the pituitary lesion and improving the function of the anterior lobe. The present case illustrates the importance of pituitary function evaluation before steroid treatment in patients with AIP.

A case of pancreatic intraepithelial neoplasia-3 with autoimmune pancreatitis.

We report a case of pancreatic intraepithelial neoplasia-3 (PanIN-3) with autoimmune pancreatitis (AIP). The patient, a 75-year-old man, had been diagnosed to have AIP with stenosis of the main pancreatic duct. After six years, computed tomography demonstrated dilatation of the main pancreatic duct in the mid-pancreas. Although we could not confirm the presence of any pancreatic tumor on the basis of imaging modalities alone, cytological examination of the pancreatic juice obtained by endoscopic retrograde pancreatography revealed atypical cells. Therefore, we performed pancreatoduodenectomy and obtained a pathologic diagnosis of PanIN-3 with AIP. The present case is informative in the context of pancreatic carcinogenesis in AIP.

High Glucose Accelerates Cell Proliferation and Increases the Secretion and mRNA Expression of Osteopontin in Human Pancreatic Duct Epithelial Cells.

BACKGROUND: The incidence of pancreatic cancer is increasing year-by-year in Japan. Among the diseases that complicate pancreatic cancer, diabetes is the most common. Recently, it has become evident that patients suffering from diabetes and obesity show increased expression of osteopontin (OPN). The purpose of this study was to investigate the effect of high glucose and high insulin culture conditions on a human pancreatic duct epithelial cell line (HPDE-6), focusing particularly on OPN expression. METHODS: HPDE-6 were cultured under various conditions, employing several combinations of glucose (normal, 6 mM high, 30 mM, and 60 mM) and insulin (0.1 nM, 1 nM) concentration. RESULTS: HPDE-6 cell proliferation was significantly accelerated under high glucose culture conditions in comparison to samples in 6 mM glucose, and was more prominent under high insulin conditions. At the same time, the expression of OPN mRNA was also increased significantly. In comparison with 6 mM glucose, the expression of 8-OHdG DNA was increased in high glucose culture. CONCLUSION: HPDE-6 cells show accelerated proliferation and increased OPN expression when cultured under high glucose and high insulin conditions. Furthermore, the cells show increased oxidative stress in the presence of high glucose.