Clinical development of a blood biomarker using apolipoprotein-A2 isoforms for early detection of pancreatic cancer.

BACKGROUND: We have previously reported apolipoprotein A2-isoforms (apoA2-is) as candidate plasma biomarkers for early-stage pancreatic cancer. The aim of this study was the clinical development of apoA2-is. METHODS: We established a new enzyme-linked immunosorbent sandwich assay for apoA2-is under the Japanese medical device Quality Management System requirements and performed in vitro diagnostic tests with prespecified end points using 2732 plasma samples. The clinical equivalence and significance of apoA2-is were compared with CA19-9. RESULTS: The point estimate of the area under the curve to distinguish between pancreatic cancer (n = 106) and healthy controls (n = 106) was higher for apoA2-ATQ/AT [0.879, 95% confidence interval (CI): 0.832-0.925] than for CA19-9 (0.849, 95% CI 0.793-0.905) and achieved the primary end point. The cutoff apoA2-ATQ/AT of 59.5 µg/mL was defined based on a specificity of 95% in 2000 healthy samples, and the reliability of specificities was confirmed in two independent healthy cohorts as 95.3% (n = 106, 95% CI 89.4-98.0%) and 95.8% (n = 400, 95% CI 93.3-97.3%). The sensitivities of apoA2-ATQ/AT for detecting both stage I (47.4%) and I/II (50%) pancreatic cancers were higher than those of CA19-9 (36.8% and 46.7%, respectively). The combination of apoA2-ATQ/AT (cutoff, 59.5 µg/mL) and CA19-9 (37 U/mL) increased the sensitivity for pancreatic cancer to 87.7% compared with 69.8% for CA19-9 alone. The clinical performance of apoA2-is was blindly confirmed by the National Cancer Institute Early Detection Research Network. CONCLUSIONS: The clinical performance of ApoA2-ATQ/AT as a blood biomarker is equivalent to or better than that of CA19-9.

Factors Associated with Overlap between Functional Dyspepsia and Nonerosive Reflux Disease in Endoscopy-based Helicobacter pylori-uninfected Japanese Health Checkup Participants: A Prospective, Multicenter Cross-sectional Study.

Objective We assessed the factors associated with overlap between functional dyspepsia (FD) and nonerosive reflux disease (NERD) in endoscopy-based Helicobacter pylori-uninfected Japanese health checkup participants. Methods We utilized baseline data from 3,085 individuals who underwent upper endoscopy for health screening in a prospective, multicenter cohort study. The participants were asked to complete a questionnaire detailing their upper abdominal symptoms and lifestyle. Anxiety was assessed using the State-Trait Anxiety Inventory (STAI) score. FD, postprandial distress syndrome (PDS), and epigastric pain syndrome (EPS) were defined according to the Rome III criteria. NERD was defined as heartburn or regurgitation ≥1 day/week without erosive esophagitis. Results Of the 3,085 participants, 73 (2.4%), 97 (3.1%), and 84 (2.7%) had FD alone, NERD alone, and FD-NERD overlap, respectively. Factors associated with FD-NERD-overlap participants compared with participants with neither FD nor NERD were women [odds ratio (OR): 2.08, 95% confidence interval (CI): 1.24-3.52], body mass index (BMI) <18.5 (OR: 2.87, 95% CI: 1.56-5.07), alcohol consumption ≥20 g/day (OR: 1.85, 95% CI: 1.06-3.15), and a high STAI score (OR: 2.53, 95% CI: 1.62-4.00). Increasing age (OR: 1.06, 95% CI: 1.01-1.11) and EPS symptoms [pure EPS (OR: 3.67, 95% CI: 1.65-8.51) and PDS-EPS overlap (OR: 11.6, 95% CI: 4.09-37.2)] were associated with FD-NERD overlap vs. FD alone. Women (OR: 3.17, 95% CI: 1.47-7.04), BMI <18.5 (OR: 3.03, 95% CI: 1.04-9.90), and acid reflux symptoms ≥2 days a week (OR: 3.57, 95% CI: 1.83-7.14) were associated with FD-NERD overlap vs. NERD alone. Conclusion Understanding the clinical features of overlap between FD and NERD will lead to better management.

Endoscopic biliary ethanol ablation using a novel multi-hole balloon catheter: In vivo feasibility study in a swine model.

BACKGROUND: Minimally invasive local treatment could be a good option for the treatment of extrahepatic cholangiocarcinoma (eCCA). This study aimed to evaluate the feasibility of a novel local treatment method, endoscopic biliary ethanol ablation (EA), in vivo using a swine model. METHODS: This study utilized a prototype of the newly developed multi-hole balloon catheter. The swine bile duct was ablated using this balloon via the same approach as the conventional endoscopic retrograde cholangiography procedure. The study outcomes included technical success, clinical success, and adverse events associated with endoscopic biliary EA. RESULTS: Fourteen miniature pigs underwent endoscopic biliary EA. Technical success was achieved for all endoscopic EA procedures without any hindrance. All pigs were reared and followed up for a median 35-day period after the procedure. No change was observed in the bile duct wall in one case, in which sufficient contact was not achieved between the balloon and bile duct wall. Except for this case, stricture formation occurred at the site of ablation, where the epithelium was sloughed and necrosis with denaturation replaced the granulation tissue and fibrotic changes. The median length and depth of the ablation area were 17.05 and 2.21 mm, respectively. No adverse events were observed, except for the formation of bile duct strictures and sequelae associated with strictures. CONCLUSIONS: This preliminary study was the first to report endoscopic biliary EA using a novel multi-hole balloon catheter, which demonstrated technical feasibility and potential for the treatment for eCCA.

STNM01, the RNA oligonucleotide targeting carbohydrate sulfotransferase 15, as second-line therapy for chemotherapy-refractory patients with unresectable pancreatic cancer: An open label, phase I/IIa trial.

Background: The impact of stroma-targeting therapy on tumor immune suppression is largely unexplored. An RNA oligonucleotide, STNM01, has been shown to repress carbohydrate sulfotransferase 15 (CHST15) responsible for tumor proteoglycan synthesis and matrix remodeling. This phase I/IIa study aimed to evaluate the safety and efficacy of STNM01 in patients with unresectable pancreatic ductal adenocarcinoma (PDAC). Methods: This was an open-label, dose-escalation study of STNM01 as second-line therapy in gemcitabine plus nab-paclitaxel-refractory PDAC. A cycle comprised three 2-weekly endoscopic ultrasound-guided locoregional injections of STNM01 at doses of 250, 1,000, 2,500, or 10,000 nM in combination with S-1 (80-120 mg twice a day for 14 days every 3 weeks). The primary outcome was the incidence of dose-liming toxicity (DLT). The secondary outcomes included overall survival (OS), tumor response, changes in tumor microenvironment on immunohistopathology, and safety (jRCT2031190055). Findings: A total of 22 patients were enrolled, and 3 cycles were repeated at maximum; no DLT was observed. The median OS was 7.8 months. The disease control rate was 77.3%; 1 patient showed complete disappearance of visible lesions in the pancreas and tumor-draining lymph nodes. Higher tumoral CHST15 expression was associated with poor CD3+ and CD8+ T cell infiltration at baseline. STNM01 led to a significant reduction in CHST15, and increased tumor-infiltrating CD3+ and CD8+ T cells in combination with S-1 at the end of cycle 1. Higher fold increase in CD3+ T cells correlated with longer OS. There were 8 grade 3 adverse events. Interpretation: Locoregional injection of STNM01 was well tolerated in patients with unresectable PDAC as combined second-line therapy. It prolonged survival by enhancing T cell infiltration in tumor microenvironment. Funding: The present study was supported by the Japan Agency for Medical Research and Development (AMED).

Examining the efficacy and safety of endobiliary radiofrequency ablation for ingrowth occlusion after metal stent placement using a bovine model.

BACKGROUND: Although endobiliary radiofrequency ablation (RFA) may be an option for the treatment of ingrowth occlusion after self-expandable metal stent (SEMS) deployment, its utility remains uncertain. This study aimed to clarify its utility and safety using bovine liver. METHODS: A prototype multifunctional RFA catheter and conventional uncovered SEMS were employed in this experimental study. We devised three model types: the ingrowth-ablation, ingrowth-ablation with stent-wire contact (created such that the electrodes were in contact with the metal stent-wire), and standard-ablation models (control). The study outcome was the ablation depth associated with RFA, which was compared among the three models. RESULTS: Thirty-six ablation procedures were conducted (12 for each of the 3 models). In the unipolar mode, the median ablation depth with the stent-wire contact model (1.0 mm) was significantly lower than that of the ingrowth-ablation (2.0 mm, p = 0.005) and standard-ablation models (2.3 mm, p = 0.004). There was no significant difference between the ingrowth-ablation and standard-ablation models (p = 0.563). In the bipolar mode, the median ablation depth with the stent-wire contact model (1.0 mm) was also significantly lower than that of the ingrowth-ablation (2.1 mm, p = 0.008) and standard-ablation models (2.0 mm, p = 0.011), and there was no significant difference between the ingrowth-ablation and standard-ablation models (p = 0.807). Scorching around the stent-wire was not observed in any specimen. CONCLUSIONS: In this ex vivo study, endobiliary RFA for ingrowth occlusion can be considered a useful modality, but the ablation effect is diminished when the electrode comes into contact with the stent-wire.

A Prospective Multicenter Randomized Feasibility Trial of Double-guidewire Techniques for Difficult Biliary Cannulation Comparing a New Double-guidewire-supported Sphincterotome (MagicTome) to a Conventional Device.

Objective To evaluate the effectiveness and safety of the double-guidewire technique (DGT) using a new double-guidewire-supported sphincterotome (MagicTome) for patients who required endoscopic retrograde cholangiopancreatography (ERCP) for biliary cannulation. Methods This prospective multicenter randomized feasibility trial involved patients with difficult biliary cannulation at any of the three study sites from June 2017 to October 2018. Patients were assigned to the DGT with MagicTome (MDGT) initially performed group and the conventional DGT (CDGT) initially performed group. The success rates of biliary cannulation by MDGT and CDGT and the ERCP-related complications were evaluated. Results Twenty-eight patients were included in this study. No significant difference was observed in the success rates of first attempts and crossover attempts between the groups (p=0.69 and p=1.00). Furthermore, no significant difference was observed in the success rate of biliary cannulation between MDGT and CDGT (62.5% and 75.0%, respectively; p=0.48). CDGT was successful in two of four patients with malignant biliary obstruction. MDGT was successful in all four patients with malignant biliary obstruction, including the two for whom CDGT was unsuccessful. Post-ERCP pancreatitis occurred in only one MDGT case. Conclusion MDGT is safe for biliary cannulation and can be used in cases where biliary cannulation by CDGT is difficult.

Current status of diagnostic and therapeutic colonoscopy in Japan: The Japan Endoscopic Database Project.

OBJECTIVES: The Japan Endoscopy Database Project was initiated to develop the world's largest endoscopy data repository. This study describes the first phase of the colonoscopy project in Japan. METHODS: Data were aggregated offline by integrating information from the endoscopy database software from January 2015 through March 2017. The study population included all patients who underwent colonoscopy at eight centers. RESULTS: A total of 31,395 patients who underwent 38,497 colonoscopy procedures were registered. The majority of procedures were performed for screening (n = 14,156), followed by fecal immunochemical test positivity (n = 3960), abdominal symptoms (n = 3864), post-colorectal surgery surveillance (n = 3431), post-endoscopic treatment surveillance (n = 3757), thorough pre-treatment examination (n = 2822), and therapeutic purposes (n = 6507). In the screening group, advanced cancers, early cancers, and adenomas were diagnosed endoscopically in 2.1%, 1.3%, and 28.7% of cases, respectively, while in the fecal immunochemical test-positive group, they were diagnosed in 2.5%, 1.9%, and 41.6% of cases, respectively. The incidence of complications was 0.177% and 0.152% in the screening and fecal immunochemical test-positive groups, respectively. The therapeutic procedures included 1446 cold forceps polypectomy procedures, 4770 cold snare polypectomy procedures, 368 hot biopsies, 2998 hot snare polypectomy procedures, 9775 endoscopic or piecemeal endoscopic mucosal resections, and 1660 endoscopic submucosal dissections. A total of 173 procedure-related complications (0.82%) occurred in 21,017 therapeutic procedures performed in 15,744 patients. CONCLUSIONS: The first phase of the Japan Endoscopy Database Project established the proportions of the diagnostic and therapeutic colonoscopy procedures, and complication rates in real-world settings.

Prospective Study Using Plasma Apolipoprotein A2-Isoforms to Screen for High-Risk Status of Pancreatic Cancer.

Apolipoprotein A2-ATQ/AT (apoA2-ATQ/AT) has been identified as a minimally invasive biomarker for detecting pancreatic cancer (PC) and high-risk (HR) individuals for PC. To establish an efficient enrichment strategy for HR, we carried out a plasma apoA2-ATQ/AT level-based prospective screening study among the general population. The subjects for the screening study were recruited at six medical check-up facilities in Japan between October 2015 and January 2017. We evaluated the positive predictive value (PPV) of the plasma apoA2-ATQ/AT level of ≤35 µg/mL for detecting PC and HR. Furthermore, we prospectively confirmed its diagnostic accuracy with another post-diagnosis population in a cross-sectional study. We enrolled 5120 subjects in experimental screening, with 84 subjects (1.3%) showing positive results for apoA2-ATQ/AT. Pancreatic abnormalities were recognized in 26 of the 84 subjects from imaging examinations. Pancreatic abnormalities detected included 1 PC and 15 HR abnormalities, such as cystic lesions including intraductal papillary mucinous neoplasm. The PPV of apoA2-ATQ/AT for detecting PC and HR was 33.3%. Moreover, a combination study with another cross-sectional study revealed that the area under the curve for apoA2-ATQ/AT to distinguish PC from healthy controls was 0.903. ApoA2-ATQ/AT has the potential to enrich PC and HR by increasing the diagnostic probability before imaging examinations.

Novel Autoantibody Signatures in Sera of Patients with Pancreatic Cancer, Chronic Pancreatitis and Autoimmune Pancreatitis: A Protein Microarray Profiling Approach.

Identification of disease-associated autoantibodies is of high importance. Their assessment could complement current diagnostic modalities and assist the clinical management of patients. We aimed at developing and validating high-throughput protein microarrays able to screen patients' sera to determine disease-specific autoantibody-signatures for pancreatic cancer (PDAC), chronic pancreatitis (CP), autoimmune pancreatitis and their subtypes (AIP-1 and AIP-2). In-house manufactured microarrays were used for autoantibody-profiling of IgG-enriched preoperative sera from PDAC-, CP-, AIP-1-, AIP-2-, other gastrointestinal disease (GID) patients and healthy controls. As a top-down strategy, three different fluorescence detection-based protein-microarrays were used: large with 6400, intermediate with 345, and small with 36 full-length human recombinant proteins. Large-scale analysis revealed 89 PDAC, 98 CP and 104 AIP immunogenic antigens. Narrowing the selection to 29 autoantigens using pooled sera first and individual sera afterwards allowed a discrimination of CP and AIP from PDAC. For validation, predictive models based on the identified antigens were generated which enabled discrimination between PDAC and AIP-1 or AIP-2 yielded high AUC values of 0.940 and 0.925, respectively. A new repertoire of autoantigens was identified and their assembly as a multiplex test will provide a fast and cost-effective tool for differential diagnosis of pancreatic diseases with high clinical relevance.

Significance of pancreatic calcification on preoperative computed tomography of intraductal papillary mucinous neoplasms.

BACKGROUND AND AIM: Chronic pancreatitis is a risk factor for pancreatic cancer. Pancreatic calcification is a characteristic of chronic pancreatitis; however, its significance for intraductal papillary mucinous neoplasm (IPMN) oncogenesis remains unknown. Therefore, we investigated the relationship between pancreatic calcification and invasive IPMN. METHODS: This study included 157 patients who underwent resection for IPMN between April 2001 and October 2016 (intraductal papillary mucinous adenoma, n = 76; noninvasive intraductal papillary mucinous carcinoma [IPMC], n = 32; and invasive IPMC, n = 49). We divided the subjects on the basis of the presence/absence of pancreatic calcification on preoperative computed tomography (CT). The factors associated with pancreatic calcification were investigated in univariate analyses. Then, multivariate logistic regression analyses of the relationship between pancreatic calcification and invasive IPMC (after adjusting for clinical or imaging characteristics) were conducted. RESULTS: Preoperative CT revealed pancreatic calcification in 17.2% (27/157) of the resected IPMN. In the univariate analyses, jaundice, high serum carbohydrate antigen 19-9 levels, and invasive IPMC were significantly associated with pancreatic calcification (4/27 [14.8%] vs 4/130 [3.1%], 0.01; 12/27 [44.4%] vs 31/130 [23.8%], 0.03; and 15/27 [55.6%] vs 34/130 [26.2%], 0.001, respectively). Pancreatic calcification was significantly associated with invasive IPMC (multivariate odds ratio = 2.88, 95% confidence interval [95% CI] = 1.15-7.21, 0.03, adjusted for clinical characteristics; odds ratio = 5.50, 95% CI = 1.98-15.3, 0.001, adjusted for imaging characteristics). CONCLUSIONS: Pancreatic calcification on CT is associated with invasive IPMC. Pancreatic calcification might be a predictor of invasive IPMC.

Evaluation of efficacy of pancreatic juice cytology for risk classification according to international consensus guidelines in patients with intraductal papillary mucinous neoplasm; a retrospective study.

OBJECTIVES: Pancreatic juice cytology (PJC) for intraductal papillary mucinous neoplasm (IPMN) is a possible tool to enhance preoperative diagnostic ability by improving risk classification for malignant IPMN, but its efficacy is controversial. This study evaluated the efficacy of PJC for risk classification according to international guidelines. METHODS: We retrospectively analyzed 127 IPMN patients who underwent endoscopic retrograde cholangiopancreatography (ERCP) preoperatively. PJC was performed in 125 of the 127 cases. High-risk stigmata (HRS, n = 57), worrisome features (WF, n = 64), and other characteristics (n = 6) were classified according to the 2017 international guidelines. RESULTS: Among the 127 IPMN patients, 71 (55.9%) had malignant IPMN (invasive and non-invasive intraductal papillary mucinous carcinoma). The accuracy of WF for classifying malignant IPMN was increased by the addition of PJC, but the accuracy of HRS was not (WF to WF + PJC: 33.1% [42/127] to 48.8% [61/125], HRS to HRS + PJC: 65.4% [83/127] to 52.8% [66/125]). Post-ERCP pancreatitis (PEP) occurred in 32 (25.2%) of 127 IPMN patients. Severe PEP was not detected. Significant risk factors for PEP were female sex, obesity, and endoscopic naso-pancreatic drainage (ENPD) (P = .03, P = .0006, and P = .02, respectively). In patients with ENPD tube placement, a main pancreatic duct size of <5 mm was a significant risk factor for PEP (P = .02). CONCLUSION: PJC could increase the accuracy of WF for classifying malignant IPMN. The additive effect of PJC for risk classification may be limited, however, and it is not recommended for all IPMN cases due to the high frequency of PEP.

Current status of esophageal endoscopy including the evaluation of smoking and alcohol consumption in Japan: an analysis based on the Japan endoscopy database.

PURPOSE: The aim was to investigate the current status of esophageal endoscopy, including the evaluation of smoking and alcohol consumption, in Japan. METHODS: A total of 47,441 patients who underwent 69,748 sessions of esophageal endoscopy were registered in the Japan Endoscopy Database between January 2015 and March 2017. The study variables were as follows: (1) methods for monitoring the esophagus and the time required for monitoring and (2) the status of smoking and alcohol consumption in patients with esophageal cancer and head and neck cancer. RESULTS: Image-enhanced endoscopy was performed in 10.6%, Lugol chromoendoscopy in 4.1%, and magnifying endoscopy in 3.2%. The mean time required for gastrointestinal endoscopy was 10 min 58 s. The mean examination times in patients with or without monitoring of the head and neck were 10 min 51 s and 11 min 13 s, respectively. In 57.0% of the patients with esophageal cancer, the head and neck were monitored at the time of gastrointestinal endoscopy. The proportion of current smokers (esophageal cancer: 16.8-4.7%; head and neck cancer: 24.3-9.3%) and addicted drinkers (esophageal cancer: 52.3-40.8%; head and neck cancer: 50.2-47.3%) were lower at the second or subsequent endoscopy than at the initial endoscopy. CONCLUSIONS: The new strategy for esophageal endoscopy has led to an evolutionary change in Japan. The patients with esophageal cancer and head and neck cancer who underwent a second or subsequent endoscopy had lower incidences of smoking and alcohol consumption, although the incidences remained high.

The Effects of Direct Oral Anticoagulants, Warfarin, Aspirin and Thienopyridine on the Performance of Immunochemical, Faecal, Occult Blood Tests.

AIM: To clarify whether antithrombotic drugs affect diagnosis using the immunochemical faecal occult blood test -(iFOBT) of colorectal neoplasia. METHODS: Using the Japan Endoscopy Database from 8 centres between 2015 and 2017, we analyzed data about patients who were iFOBT positive and had received direct oral anticoagulants (DOAC), warfarin, aspirin or thienopyridine. One-to-one matching-analogue propensity score weighted analyses were performed to compare the positive predictive value (PPV) of all neoplasms, invasive and non-invasive colorectal cancers and adenomas between drug users and non-users. All neoplasms included invasive and non-invasive colorectal cancer, and adenomas. RESULTS: We analyzed 197 DOAC users and 196 non-users, 153 warfarin users and 153 non-users, 408 aspirin users and 415 non-users, and 97 thienopyridine users and 97 non-users. No significant differences were observed in the PPV for all neoplasms (56.67 vs. 50.43%), invasive cancer (4.32 vs. 3.53%), non-invasive cancer (15.58 vs. 15.56%) or adenoma (53.13 vs. 48.09%) between the DOAC user and non-user groups. No significant differences were observed in the PPV for all neoplasia, invasive and non-invasive cancer, or adenoma between warfarin, aspirin and thienopyridine use and non-users. CONCLUSIONS: DOAC, warfarin, aspirin and thienopyridine use did not decrease the PPVs of the iFOBT used to evaluate all colorectal neoplasia.

Factors associated with the presentation of erosive esophagitis symptoms in health checkup subjects: A prospective, multicenter cohort study.

BACKGROUND: We aimed to clarify the factors associated with the presentation of erosive esophagitis (EE) symptoms in subjects undergoing health checkups. METHODS: We utilized baseline data from 7,552 subjects who underwent upper endoscopy for health screening in a prospective, multicenter cohort study. The subjects were asked to complete a questionnaire detailing their upper abdominal symptoms and lifestyle. Based on the heartburn and/or acid regurgitation frequency, the EE subjects were stratified into the following three groups: (1) at least one day a week (symptomatic EE [sEE]), (2) less than one day a week (mild symptomatic EE [msEE]), and (3) never (asymptomatic EE [aEE]). Postprandial distress syndrome (PDS) and epigastric pain syndrome (EPS) were defined according to the Rome III criteria. RESULTS: Of the 1,262 (16.7%) subjects (male 83.8%, mean age 52.6 years) with EE, the proportions of sEE, msEE and aEE were 15.0%, 37.2% and 47.9%, respectively. The sEE group showed significant associations with overlapping EPS (OR: 58.4, 95% CI: 25.2-160.0), overlapping PDS (OR: 9.96, 95% CI: 3.91-26.8), severe hiatal hernia (OR: 2.43, 95% CI: 1.43-4.05), experiencing high levels of stress (OR: 2.20, 95% CI: 1.43-3.40), atrophic gastritis (OR: 1.57, 95% CI: 1.03-2.36) and Los Angeles (LA) grade B or worse (OR: 1.72, 95% CI: 1.12-2.60) in the multivariate analysis. CONCLUSIONS: Approximately one-sixth of EE subjects were symptomatic. A multifactorial etiology, including factors unrelated to gastric acid secretion, was associated with the symptom presentation of EE subjects.

Multifocal cysts and incidence of pancreatic cancer concomitant with intraductal papillary mucinous neoplasm.

OBJECTIVES: The present study was conducted in order to elucidate the relationship between the number of cyst-existing regions and incidence of pancreatic ductal adenocarcinoma (PDAC) concomitant with intraductal papillary mucinous neoplasm (IPMN), which currently remains unclear. METHODS: Subjects comprised 141 patients undergoing resection for IPMN (Non-invasive IPMN (IPMN with low-to high-grade dysplasia): N = 94, invasive IPMN: N = 31, and PDAC concomitant with IPMN: N = 16) between November 2000 and February 2017. A logistic regression analysis was performed to assess the relationship between the number of cyst-existing regions (one region/two or more regions) and incidence of PDAC concomitant with IPMN, adjusted by clinical characteristics. Cyst-existing regions were defined by the number of anatomical parts of the pancreas: the head/body/tail of the pancreas. RESULTS: Multiple cyst-existing regions (two or more regions) correlated with the incidence of PDAC concomitant with IPMN (PDAC concomitant with IPMN in one region vs. two or more regions: 3/66 vs. 13/75, multivariable odds ratio [OR] = 4.11, 95% confidence interval [CI] = 1.22 to 18.8, P = 0.02). In contrast, multiple cyst-existing regions did not correlate with the incidence of IPMN (invasive IPMN in one region vs. two or more regions: 13/66 vs. 18/75, OR = 1.19, 95% CI = 0.52 to 2.76, P = 0.67). CONCLUSIONS: Multifocal cysts correlated with the incidence of PDAC concomitant with IPMN, and may be a high-risk factor for PDAC concomitant with IPMN.

Serum apolipoprotein A2 isoforms in autoimmune pancreatitis.

Recently, apolipoprotein A2 (apoA2) isoforms have been reported as candidate serum/plasma biomarkers of pancreatic cancer. However, the distribution of apoA2 isoforms in patients with autoimmune pancreatitis (AIP) has not been investigated yet. In this study, we evaluated the distribution of serum apoA2 isoforms; i.e., homodimer apoA2-ATQ/ATQ, heterodimer apoA2-ATQ/AT, and homodimer apoA2-AT/AT, in AIP patients and healthy volunteers (HV) using enzyme-linked immunosorbent assays, and the clinical characteristics and serum levels of each apoA2 isoform in 32 AIP patients and 38 HV were investigated. The calculated apoA2-ATQ/AT levels of the AIP patients were significantly lower than those of the HV, which agreed with results obtained for patients with pancreatic cancer. Interestingly, most of the AIP patients exhibited high levels of apoA2-ATQ along with low levels of apoA2-AT, indicating that the processing of the C-terminal regions of apoA2 dimer was inhibited in the AIP patients. This specific distribution of serum apoA2 isoforms might provide important information about the disease states of AIP patients and aid the differential diagnosis of AIP versus pancreatic cancer.