Skeletal muscle mass and function are affected by pancreatic atrophy, pancreatic exocrine insufficiency and poor nutritional status in patients with chronic pancreatitis.

BACKGROUND/OBJECTIVE: Previous studies have demonstrated that sarcopenia is frequently observed in patients with chronic pancreatitis (CP). However, most studies have defined sarcopenia solely based on skeletal muscle (SM) loss, and muscle weakness such as grip strength (GS) reduction has not been considered. We aimed to clarify whether SM loss and reduced GS have different associations with clinical characteristics and pancreatic imaging findings in patients with CP. METHODS: One hundred two patients with CP were enrolled. We defined SM loss by the SM index at the third lumbar vertebra on CT (<42 cm2/m2 for males and <38 cm2/m2 for females), and reduced GS by < 28 kg for males and <18 kg for females. RESULTS: Fifty-seven (55.9 %) patients had SM loss, 21 (20.6 %) had reduced GS, and 17 (16.7 %) had both. Patients with SM loss had lower body mass index, weaker GS, higher Controlling Nutritional Status score, lower serum lipase level, and lower urinary para-aminobenzoic acid excretion rate, suggesting worse nutritional status and pancreatic exocrine insufficiency. On CT, main pancreatic duct dilatation and parenchymal atrophy were more frequent in patients with SM loss than in those without it. Patients with reduced GS were older and had worse nutritional status than those without it. CONCLUSIONS: SM loss was associated with pancreatic exocrine insufficiency, low nutritional status, and pancreatic imaging findings such as parenchymal atrophy and main pancreatic duct dilatation, whereas older age and low nutritional status led to additional reduced GS.

Trends and clinical characteristics of pediatric acute pancreatitis patients in Japan: A comparison with adult cases based on a national administrative inpatient database.

BACKGROUND: /Objectives: Pediatric acute pancreatitis (AP) is not as rare as previously thought, and an increased incidence thereof has been reported. We aimed to clarify the trends and clinical characteristics of pediatric AP in Japan. METHODS: We utilized the Japanese Diagnosis Procedure Combination inpatient database for patients admitted between April 2012 and March 2021, and extracted the data of patients whose principal diagnosis was AP (ICD-10 code K85) or in whom AP accounted for most of the medical expenses. Patients were classified into pediatric (≤18 years) and adult (age >18 years) groups. RESULTS: We included 3941 AP cases in pediatrics and 212,776 in adults. AP cases accounted for 0.08 % of all admissions in pediatrics and 0.33 % in adults, with upward trends during the study period. The proportion of AP patients among all admissions was increased with advancing age in pediatrics. Compared to adults, pediatric AP patients had a smaller proportion of severe cases (22.9 % vs. 28.7 %; P < 0.001), fewer interventions for late complications (0.2 % vs. 1.3 %; P < 0.001), shorter hospital stays (mean 16.6 days vs. 18.0 days; P = 0.001), lower overall mortality (0.7 % vs. 2.9 %; P < 0.001), and lower mortality in severe cases (1.3 % vs. 5.6 %; P < 0.001). Pediatric cases were more frequently transferred from other institutions and treated at academic hospitals than adults (both P < 0.001). CONCLUSIONS: There was an upward trend in the proportion of AP among all admissions in pediatrics, with a lower risk of complications and mortality than adult cases.

Severity of acute pancreatitis in patients with inflammatory bowel disease in the era of biologics: A propensity-score-matched analysis using a nationwide database in Japan.

Background and Aim: Acute pancreatitis (AP) is a rare extraintestinal manifestation of inflammatory bowel disease (IBD). Several studies from Western countries have reported that the severity of AP in patients with IBD is similar to that in the general population; however, its severity in patients from Eastern countries in the era of biologics remains unclear. This study aimed to investigate the severity of AP in patients with IBD and the effect of biologics on the severity of AP using a nationwide database. Methods: We divided 1138 eligible AP admissions from the Diagnosis Procedure Combination database system into IBD and non-IBD groups after propensity score matching, and compared the severity of AP. We divided the IBD group into ulcerative colitis (UC) and Crohn's disease (CD) subgroups and compared each with the non-IBD group. Logistic regression analysis was conducted to identify the clinical factors affecting acute pancreatitis. Results: IBD and UC groups had lower rate of severe AP compared to the non-IBD group (13.7% vs 28.3%, P < 0.0001 and 11.0% vs 28.3%, P < 0.0001, respectively). There were no differences in the rates of severe AP between the CD and non-IBD groups. Multivariate analysis showed that biologics did not affect the severity of AP. Conclusion: The severity of AP in patients with IBD may be lower than that in the general population; biologics for IBD may not worsen its severity. Further prospective studies are required to clarify the severity of AP in patients with IBD.

The M-ANNHEIM-AiP-Activity-Score is useful for predicting relapse in patients with type 1 autoimmune pancreatitis.

BACKGROUND/OBJECTIVES: Proper assessment of disease activity and prediction of relapse are crucial for the management of autoimmune pancreatitis (AIP). The M-ANNHEIM-AiP-Activity-Score (MAAS) has been proposed to determine disease activity and predict relapse in German and Swedish patients with AIP. MAAS is calculated using six categories: pain report, pain control, exocrine insufficiency, endocrine insufficiency, imaging, and complications. This study aimed to clarify the usefulness of MAAS to predict relapse in Japanese patients with type 1 AIP. METHODS: We retrospectively analyzed 117 patients with type 1 AIP undergoing initial and maintenance steroid treatments at our institute between April 2006 and March 2021. AIP was diagnosed according to the Japanese Diagnostic Criteria for AIP 2018. We examined the association of MAAS with relapse during and after maintenance treatment. RESULTS: MAAS (median, 8 points) at the start of the initial treatment was reduced after treatment (median, 4 points; P < 0.001). A MAAS ≥11 points at the start of the initial treatment was associated with relapse. The initial treatment-induced reduction of MAAS<60% was more frequent in patients with relapse (75.0%) than in patients without relapse (37.6%; P = 0.007). MAAS at the start of maintenance treatment was higher for patients with relapse (median, 5 points) than that for patients without relapse (median, 4 points; P = 0.007). MAAS ≥4 points at the start of maintenance treatment was associated with subsequent relapse. CONCLUSIONS: MAAS is useful for predicting relapse in patients with type 1 AIP undergoing maintenance therapy.

A case of occult pancreaticobiliary reflux due to endoscopically confirmed relaxation of the Oddi sphincter.

An otherwise healthy 45-year-old woman had been experiencing intermittent right upper abdominal pain for the past 1 year. Computed tomography showed pneumobilia and pancreatic duct emphysema despite a normal duodenal papilla. Magnetic resonance cholangiopancreatography and endoscopic ultrasound confirmed bile duct dilation but without a pancreaticobiliary maljunction. Duodenoscopy detected a slightly sunken, unfixed, and spontaneously enlarged duodenal papilla. During the cholangiogram, the Oddi sphincter was relaxed and the catheter could be easily inserted into the bile duct. Further, no findings suggestive of pancreaticobiliary maljunction were observed, and the contrast medium leaked spontaneously from the duodenal papilla. As biliary amylase level was high, we surmised the occurrence of occult pancreaticobiliary reflux due to relaxation of the Oddi sphincter. However, as there are no guidelines on the management of this condition, we did not offer any treatment. Nevertheless, the patient continued to experience similar symptoms and was retested 1 year later with similar results. As occult pancreaticobiliary reflux was reconfirmed, we suggested that the patient undergo laparoscopic extrahepatic bile duct resection and cholecystectomy, which is the standard treatment for pancreaticobiliary maljunction. Pathological evaluation revealed fibrous thickening of the bile duct wall and chronic cholecystitis, which are typical findings of pancreaticobiliary reflux. Even though pancreaticobiliary reflux is mainly observed in pancreaticobiliary maljunction, it has also been reported in normal patients. Here, we describe a novel mechanism of pancreaticobiliary reflux, namely, a relaxed or defective Oddi sphincter.

Utility of Endoscopic Ultrasound-Guided Fine-Needle Aspiration and Biopsy for Histological Diagnosis of Type 2 Autoimmune Pancreatitis.

In Japan, type 1 autoimmune pancreatitis (AIP) is the most common type of AIP; type 2 AIP is rare. The aim of this study was to clarify the usefulness of endoscopic ultrasound-guided fine-needle aspiration and biopsy (EUS-FNAB) for the diagnosis of type 2 AIP. We analyzed the tissue specimens of 10 patients with suspected type 2 AIP who underwent EUS-FNAB at our hospital between April 2009 and March 2021 for tissue volume and histopathological diagnostic performance. The male-to-female ratio of the patients was 8:2, and the patient age (mean ± standard deviation) was 35.6 ± 15.5 years. EUS-FNAB provided sufficient tissue volume, with high-power field >10 in eight patients (80.0%). Based on the International Consensus Diagnostic Criteria (ICDC), four patients (40.0%) had histological findings corresponding to ICDC level 1, and five patients (50.0%) had histological findings corresponding to ICDC level 2. The results of this study show that EUS-FNB can be considered an alternative method to resection and core-needle biopsy for the collection of tissue samples of type 2 AIP.

Pancreatic mixed acinar-neuroendocrine carcinoma in a patient with a germline BRCA2 mutation: a case report.

Loss of function in the BRCA2 gene exacerbates ovarian, breast, and pancreatic ductal cancer risk. Despite being implicated in the pancreatic ductal epithelium carcinogenesis, the involvement of a germline BRCA2 mutation in acinar and endocrine cells is less reported. A 45-year-old woman with a history of breast cancer was referred to our hospital for a detailed examination of epigastric pain. Her father had pancreatic cancer, and her paternal aunt had a history of breast cancer. Contrast-enhanced computed tomography revealed a round tumor with a contrast effect in the pancreatic head. The patient underwent pancreaticoduodenectomy, and postoperative pathology and genetic testing revealed amphicrine-type mixed acinar-neuroendocrine carcinoma with a germline BRCA2 mutation. Recent studies have reported the BRCA2 mutation in genome sequencing of pancreatic acinar cell carcinoma and neuroendocrine tumor; perhaps, genetic testing for the BRCA2 mutation is feasible for patients with mixed neuroendocrine-non-neuroendocrine neoplasm.

Acute Pancreatitis in Japan: Comparison of Before and After Revision of the Clinical Guidelines.

OBJECTIVES: Cases of acute pancreatitis (AP) are increasing worldwide, and mortality remains high in severe cases. In 2015, the Japanese guidelines for the management of AP were revised. We aimed to clarify the clinical practice of AP in Japan and its trend during the revision of the guidelines using a Japanese nationwide administrative database. METHODS: We retrospectively analyzed 102,119 patients with AP who were hospitalized between April 2014 and March 2018. The study period was divided into the first period (the time before the revision: fiscal years 2014 and 2015) and second period (after the revision: 2016 and 2017). RESULTS: Severe cases of AP accounted for 27.7% of total cases. The in-hospital mortality in severe cases was 5.7%. The mortality within 14 days of admission improved from 3.2% in the first period to 2.6% in the second period (P = 0.022). Referred patients had more severe diseases and a higher mortality. The mortality in patients who underwent endoscopic ultrasound-guided fistuloplasty for local complications (11.6%) was lower than that in patients who underwent percutaneous drainage (23.4%) or AP surgery (22.6%) (P < 0.001). CONCLUSIONS: We clarified the clinical practice of AP including the improved mortality after the revision of the guidelines.

Clinical features and prognostic impact of asymptomatic pancreatic cancer.

Pancreatic ductal adenocarcinoma (PDAC) is highly lethal, and early diagnosis is challenging. Because patients who present with symptoms generally have advanced-stage diseases, analysis of asymptomatic PDAC provides invaluable information for developing strategies for early diagnosis. Here, we reviewed 577 patients with PDAC (372 diagnosed with symptoms [symptomatic group] and 205 without symptoms [asymptomatic group]) diagnosed at our institute. Among the 205 asymptomatic PDAC patients, 109 were detected during follow-up/work-up for other diseases, 61 because of new-onset or exacerbation of diabetes mellitus, and 35 in a medical check-up. Asymptomatic PDAC is characterized by smaller tumor size, earlier disease stage, and higher resectability than those of symptomatic PDAC. In 22.7% of asymptomatic cases, indirect findings, e.g., dilatation of the main pancreatic duct, triggered PDAC detection. Although pancreatic tumors were less frequently detected, overall abnormality detection rates on imaging studies were nearly 100% in asymptomatic PDAC. Asymptomatic PDAC had a better prognosis (median survival time, 881 days) than symptomatic PDAC (342 days, P < 0.001). In conclusion, diagnosis of PDAC in the asymptomatic stage is associated with early diagnosis and a better prognosis. Incidental detection of abnormal findings during the follow-up/work-up for other diseases provides important opportunities for early diagnosis of asymptomatic PDAC.

A New Preoperative Scoring System for Predicting Aggressiveness of Non-Functioning Pancreatic Neuroendocrine Neoplasms.

The management of non-functioning pancreatic neuroendocrine neoplasms (NF-PanNENs) is still controversial. This study aimed to develop a new scoring system for treatment decisions at initial diagnosis based on the identification of the predictive factors for aggressive NF-PanNENs. Seventy-seven patients who had been pathologically diagnosed with NF-PanNENs were enrolled. We retrospectively reviewed 13 variables that could be assessed preoperatively. Univariate and multivariate stepwise logistic regression analyses were performed to identify factors for the aggressiveness of NF-PanNENs, and a scoring system was developed by assigning weighted points proportional to their ß regression coefficient. Tumor size > 20 mm on contrast-enhanced computed tomography, tumor non-vascularity, and Ki-67 labeling index ≥5% on endoscopic ultrasound-guided fine-needle aspiration specimens were identified as independent factors for predicting the aggressiveness of NF-PanNENs. The new scoring system, developed using the identified factors, had an excellent discrimination ability, with area under the curve of 0.92 (95% CI, 0.85-0.99), and good calibration (p = 0.72, Hosmer-Lemeshow test). Ten-year overall survival rates in low-risk (0 point), intermediate-risk (1 to 2 points), and high-risk (3 to 4 points) groups were 100%, 90.9%, and 24.3%, respectively. This new scoring system would be useful for treatment decisions and prognostic prediction at initial diagnosis.

High-purity Isolation for Genotyping Rare Cancer Cells from Blood Using a Microfluidic Chip Cell Sorter.

BACKGROUND/AIM: A multistep sorting method for enrichment of rare cells, such as circulating tumor cells, in the blood without cumbersome pretreatments required by most flow cytometry-based methods, which lead to high cost and decreased detection efficiency, was developed. MATERIALS AND METHODS: After only hemolysis and cell staining, cancer cells are enriched by repetitive sorting (3×) based on nuclear-positive, cytokeratin-positive, and CD45-negative expression. RESULTS: Experiments using spikes of PC-9 cells showed a mean recovery of 65% and mean purity of 83%, which was retained up to 72 hours after blood draw using preservative tubes. Significant differences in expression level of programmed death-ligand 1 or vimentin were observed between high- and low-expressing cell lines, concurrently with enrichment. Next-generation sequencing analysis of recovered PC-9, A549, and MDA-MB231 cells successfully detected all known mutations. CONCLUSION: This novel isolation method applicable for preserved samples with sufficient recovery and purity may be substantially beneficial for recovering cells for subsequent molecular analysis.

Focal Parenchymal Atrophy of the Pancreas Is Frequently Observed on Pre-Diagnostic Computed Tomography in Patients with Pancreatic Cancer: A Case-Control Study.

Pancreatic ductal adenocarcinoma (PDAC) accounts for the majority of all pancreatic cancers and is highly lethal. Focal parenchymal atrophy (FPA) of the pancreas has been reported as a characteristic imaging finding of early PDAC. Here, we reviewed 76 patients with PDAC who underwent computed tomography (CT) between 6 months and 3 years before PDAC diagnosis, as well as 76 sex- and age-matched controls without PDAC on CT examinations separated by at least 5 years. FPA was observed corresponding to the location of the subsequent tumor on pre-diagnostic CT in 14/44 (31.8%) patients between 6 months and 1 year, 14/51 (27.5%) patients between 1 and 2 years, and 9/41 (22.0%) patients between 2 and 3 years before PDAC diagnosis. Overall, FPA was more frequently observed in patients with PDAC (26/76; 34.2%) on pre-diagnostic CT than that in controls (3/76; 3.9%) (p < 0.001). FPA was observed before the appearance of cut-off/dilatation of the main pancreatic duct, suggesting that FPA might be the earliest sign of PDAC. FPA was less frequently found in tumors in the pancreatic head (3/27; 11.1%) than in those in the body (14/30; 46.7%) or tail (9/19; 47.4%). FPA may predict the subsequent PDAC diagnosis, serving as an important imaging sign for the early diagnosis of pancreatic cancer.

Longitudinal Evaluation of PD-L1 Expression on Circulating Tumor Cells in Non-Small Cell Lung Cancer Patients Treated with Nivolumab.

Although programmed death-ligand 1 (PD-L1) expression on tumor tissue is a validated predictive biomarker for a PD-1 pathway blockade in non-small cell lung cancer (NSCLC), longitudinal changes in its expression during treatment remains elusive. Circulating tumor cells (CTCs) are assumed to reflect the transition of characteristics of the primary tumor undergoing anticancer treatment. Here, we sequentially evaluated the PD-L1 expression on CTCs in NSCLC patients treated with nivolumab. Forty-five patients were enrolled, and CTCs were enriched from 3 mL of peripheral blood using a microcavity array system at baseline and weeks 4, 8, 12, and 24 or until progressive disease. The effective responses to therapy were compared between patients without progressive disease (PD) at week 8 (i.e., non-PD patients) and in those with PD between weeks 4 and 8 (PD patients) in terms of increased vs. decreased or equal CTC status at week 8 (for non-PD patients) or at the point of PD (for PD patients) compared to the baseline. Significantly more non-PD patients were classified as decreased or equal in number and proportion to PD-L1-positive CTCs among the detected CTCs (PD-L1 positivity rates) (p < 0.05). Moreover, progression-free survival was significantly longer in patients with ≥7.7% PD-L1 positivity rates (n = 8) than in those with <7.7% rates (n = 8; p < 0.01) at week 8. These results suggest the predictive significance of the early evaluation of PD-L1 expression on CTCs for maintaining the benefits from nivolumab treatment.

Acinar Cell Carcinoma with Morphological Change in One Month.

A 64-year-old man was admitted to our hospital to undergo examination of a pancreatic tumor accompanied by sudden epigastric pain. The tumor had a well-defined oval shape that was mostly less enhanced, with the exception of part of the tumor on the pancreatic head side, on contrast enhanced (CE)-CT. However, CE-CT performed one-month later revealed that the viable part of the tumor grew toward the pancreatic tail with the reduction of necrotic tissue. We performed distal pancreatectomy and the tumor was diagnosed as acinar cell carcinoma (ACC). One important characteristic of ACC is that it may develop morphological changes within a short period of time.

IgG4-related Diaphragmatic Inflammatory Pseudotumor.

A 71-year-old man underwent surgery for a pancreatic neuroendocrine tumor. Follow-up imaging showed swelling of the remnant pancreas, and he was histologically diagnosed with autoimmune pancreatitis based on endoscopic ultrasonography-guided fine-needle aspiration specimens. After two years, a tumor appeared on the liver surface. Although we planned to perform laparoscopic partial hepatectomy, the intraoperative findings showed that the tumor was located in the diaphragm. Partial resection of the diaphragm was performed, and the final diagnosis was an immunoglobulin G4-related inflammatory pseudotumor in the diaphragm. To our knowledge, this is the first reported case of an immunoglobulin G4-related diaphragmatic inflammatory pseudotumor.

New-Onset or Exacerbation of Diabetes Mellitus Is a Clue to the Early Diagnosis of Pancreatic Cancer.

Pancreatic ductal adenocarcinoma (PDAC), which accounts for majority of pancreatic cancers, is one of the most lethal human malignancies. Most patients are diagnosed at an advanced stage after symptom development. Early diagnosis of PDAC in asymptomatic subjects is important to improve prognosis. Diabetes mellitus (DM) is a risk factor for PDAC, and DM, especially new-onset DM, has attracted attentions as a diagnostic clue to PDAC. However, the impact of DM as a diagnostic opportunity on the prognosis of PDAC is unclear. We here retrospectively reviewed 489 PDAC patients and compared the clinical characteristics and prognosis according to the opportunities for PDAC diagnosis. PDAC was diagnosed upon presentation of symptoms, such as pain and jaundice, in 318 cases including 151 DM patients, upon new-onset or exacerbation of long-standing DM in 53 asymptomatic patients, and upon incidental detection by medical check-up or follow-up/work-up of other diseases in 118 asymptomatic patients. Asymptomatic patients including those with DM had smaller tumors, earlier disease stage, and higher resectability rates than symptomatic patients. Asymptomatic patients diagnosed in association with DM had better prognosis (median survival time, 771 days) than those diagnosed due to symptoms (343 days, P < 0.001), and similar to those diagnosed by incidental detection (869 days). The survival advantage was not evident in symptomatic patients with DM-associated signs. In conclusion, patients diagnosed in association with DM at asymptomatic stages had better prognosis than those diagnosed with symptoms. DM-associated signs might provide a clue to the early diagnosis of PDAC among asymptomatic subjects.

Focal Parenchymal Atrophy and Fat Replacement Are Clues for Early Diagnosis of Pancreatic Cancer with Abnormalities of the Main Pancreatic Duct.

Pancreatic cancer is one of the most dangerous solid tumors, but its early diagnosis is difficult. The abnormality of the main pancreatic duct (MPD), such as a single localized stricture and upstream dilatation, might be useful in the early detection of pancreatic cancer. However, these findings are often observed in benign inflammatory cases. This study aimed to clarify whether early pancreatic cancer presenting MPD abnormalities has characteristic features different from those of benign cases. This is a single-center, retrospective study. We analyzed 20 patients who underwent pancreatectomy presenting with a single, localized MPD stricture without identifiable masses on imaging: 10 patients with pancreatic ductal adenocarcinoma (cancer group; 6 with stage 0 and 4 with stage I) and 10 patients with benign strictures (benign group; 8 with inflammation and 2 with low-grade pancreatic intraepithelial neoplasms). Pancreatectomy was performed in these benign cases because high-grade intraepithelial neoplasm was suspected. Although the proportion of patients with diabetes mellitus tended to be higher in the cancer group (6/10) than that in the benign group (1/10) (P = 0.058), other clinical characteristics were not different between the groups. Preoperative cytological malignancies were detected in four patients in the cancer group (4/10) but not in the benign group (P = 0.09). Focal parenchymal atrophy and fat replacement were more frequently detected on computed tomography in the cancer group (7/10) than in the benign group (1/10) (P = 0.02). In conclusion, focal parenchymal atrophy and fat replacement may provide clues for the early diagnosis of pancreatic cancer.

Detection of AXL expression in circulating tumor cells of lung cancer patients using an automated microcavity array system.

Noninvasive diagnostics using circulating tumor cells (CTCs) are expected to be useful for decision making in precision cancer therapy. AXL, a receptor tyrosine kinase is associated with tumor progression, epithelial-to-mesenchymal transition (EMT), and drug resistance, and is a potential therapeutic target. However, the epithelial markers generally used for CTC detection may be not enough to detect AXL-expressing CTCs due to EMT. Here, we evaluated the detection of AXL-expressing CTCs using the mesenchymal marker vimentin with a microcavity array system. To evaluate the recovery of cancer cells, spike-in experiments were performed using cell lines with varying cytokeratin (CK) or vimentin (VM) expression levels. With high CK and low VM-expressing cell lines, PC-9 and HCC827, the recovery rate of AXL-expressing cancer cells was 1%-17% using either CK or VM as markers. Whereas, with low CK and high VM-expressing cell lines, MDA-MB231 and H1299, it was 52%-75% using CK and 72%-88% using VM as a marker. For clinical evaluation, peripheral blood was collected from 20 non-small cell lung cancer patients and CTCs were detected using CK or VM as markers in parallel. Significantly more AXL-expressing single CTCs were detected in VM-positive than CK-positive CTCs (P < .001). Furthermore, CTC clusters were identified only among VM-positive CTCs in 20% of patients. Patients with one or more prior treatments harbored significantly more VM-positive AXL-expressing CTCs, suggesting the involvement of these CTCs in drug resistance. These results indicate the necessity of integrating mesenchymal markers with CTC detection and this should be further evaluated clinically.

IgG4-related Sclerosing Cholangitis Mimicking Cholangiocarcinoma Diagnosed by Endoscopic Ultrasound-guided Fine-needle Aspiration.

A 58-year-old man was referred for obstructive jaundice. Imaging modalities revealed the presence of multiple pancreatic tumors and the stenosis of the middle common bile duct due to a hypoenhanced localized tumor. The multiple pancreatic tumors were histopathologically diagnosed as autoimmune pancreatitis by endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA). To differentiate between IgG4-related sclerosing cholangitis (IgG4-SC) and cholangiocarcinoma, we diagnosed the biliary tumor as IgG4-SC by EUS-FNA because of insufficient pathological materials obtained in a transpapillary manner. We herein report a case of IgG4-SC diagnosed by EUS-FNA.

DNA polymerase IV mediates efficient and quick recovery of replication forks stalled at N2-dG adducts.

Escherichia coli DNA polymerase IV (Pol IV, also known as DinB) is a Y-family DNA polymerase capable of catalyzing translesion DNA synthesis (TLS) on certain DNA lesions, and accumulating data suggest that Pol IV may play an important role in copying various kinds of spontaneous DNA damage including N(2)-dG adducts and alkylated bases. Pol IV has a unique ability to coexist with Pol III on the same ß clamp and to positively dissociate Pol III from ß clamp in a concentration-dependent manner. Reconstituting the entire process of TLS in vitro using E. coli replication machinery and Pol IV, we observed that a replication fork stalled at (-)-trans-anti-benzo[a]pyrene-N(2)-dG lesion on the leading strand was efficiently and quickly recovered via two sequential switches from Pol III to Pol IV and back to Pol III. Our results suggest that TLS by Pol IV smoothes the way for the replication fork with minimal interruption.