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Background The clinical characteristics of IgG4-related sclerosing cholangitis (IgG4-SC) especially without autoimmune pancreatitis (AIP) have not been investigated in a large cohort. Aims To clarify the clinical characteristics of IgG4-SC and IgG4-SC without AIP. Methods We retrospectively reviewed imaging, serology, other organ involvement (OOI) and histology of 872 patients with IgG4-SC who participated in a Japanese nationwide survey in 2019, and compared these items between IgG4-SC with and without AIP. Results AIP was present in 83.7% (730/872) of IgG4-SC. In IgG4-SC, bile duct wall thickening was observed on ultrasound (528/650; 81.2%), computed tomography (375/525; 71.4%) and magnetic resonance imaging or cholangiopancreatography (290/440; 65.9%). An elevated serum IgG4 level (≥ 135 mg/dL) was found in 88.0% (322/366). IgG4-related OOI other than AIP was observed in 25.2% (211/836). The proportion of females was significantly higher in IgG4-SC without AIP (28.9% vs. 20.1%; p = 0.025). Hilar stricture was the most common cholangiographic type in IgG4-SC without AIP (39/107; 36.4%).There were no significant differences between IgG4-SC with and without AIP in the rates of bile duct wall thickening, elevated serum IgG4 level, or IgG4-related OOI. Conclusions The clinical characteristics of IgG4-SC was similar between IgG4-SC with and without AIP in a large cohort.

Primary squamous cell carcinoma (SCC) of the liver is an extremely rare disease with a very poor prognosis. An 83-year-old woman was referred to our hospital with left abdominal pain. Laboratory data showed mildly elevated C-reactive protein and biliary enzymes. The tumor markers carcinoembryonic antigen, alpha-fetoprotein, and carbohydrate antigen 19-9 were within normal ranges. Contrast-enhanced computed tomography revealed a 60 mm-sized low-density mass with poor contrast enhancement located in the lateral segment of the liver. The tumor showed low signal on T

Bailout surgery (BOS; partial cholecystectomy, open conversion, and fundus-first approach) has been recommended for difficult cases to ensure safe performance of cholecystectomy. However, the efficacy of BOS for preventing intraoperative massive bleeding and bile duct injury (BDI) remains unclear, especially in the context of acute cholecystitis (AC). This study aimed to retrospectively validate the feasibility of BOS for AC.We enrolled 479 patients who underwent emergency cholecystectomies for AC between 2011 and 2021. Univariate and multivariate analyses were performed to detect the risk factors for BOS in patients with AC. Perioperative variables were compared between patients who underwent total cholecystectomy (TC) and those who underwent BOS. Propensity score matching analysis was performed to compare the two groups.Significant differences in American Society of Anesthesiologists physical status and Charlson Comorbidity Index scores, TG18 severity grading, white blood cell count, and albumin and C-reactive protein (CRP) levels were found between the TC and BOS groups. Preoperative CT imaging demonstrated severe inflammation evidenced by gallbladder wall thickness, enhancement of the liver bed, and duodenal edema in the BOS group compared to the TC group. Postoperative complications were significantly higher in the BOS group than in the TC group. Further, BDI was completely prevented by BOS. Multivariate analysis identified TG18 grade ≥ II, CRP ≥ 7.7, and duodenal edema as independent risk factors for BOS. After PSM analysis, postoperative complications were not worse in patients who underwent BOS rather than TC. Among BOS procedures, laparoscopic BOS (lap-BOS) was the most efficacious in preventing intraoperative blood loss and postoperative bile leakage.Severity grading II, elevated CRP levels, or duodenum edema revealed by CT were determined to be risk factors impeding total cholecystectomy. BOS is a safe, feasible, and efficacious procedure for preventing BDI. Among BOS procedures, lap-BOS showed better postoperative outcomes.

Hamartomas in the pancreas are rare and are often histologically and morphologically similar to solitary fibrous tumours (SFTs). We examined the differences between hamartomas and SFTs at the molecular level. METHODS AND RESULTS: Thirteen patients histopathologically diagnosed with pancreatic hamartoma were included in the study. We also performed STAT6 immunohistochemistry (IHC), which is used in the diagnosis of SFT. Furthermore, for the three cases in which RNA was extracted, reverse transcription polymerase chain reaction to search for NAB2::STAT6 fusions was used. Macroscopically, 13 patients had well-demarcated tumour lesions. Histologically, no islets of Langerhans were observed in the lesions, acinar tissue and ducts were unevenly distributed and elastic fibres were not observed around the ducts by Elastica van Gieson staining. One case contained a lipomatous hamartoma composed mainly of adipose tissue. Seven of the 13 cases demonstrated expression of STAT6 in the nuclei of intervening spindle cells. NAB2::STAT6 fusions were observed in two of the three cases in which RNA was extracted. These two cases also demonstrated STAT6 expression in spindle cells using STAT6 IHC. In one case of lipomatous hamartoma, we did not confirm NAB2::STAT6 fusion or STAT6 expression in STAT6 IHC. CONCLUSION: Of the 13 patients histopathologically diagnosed with hamartoma, two demonstrated NAB2::STAT6 fusions, suggesting the existence of pancreatic hamartomas with molecular-level components identical to those of SFT.

Background and Aims: The subtypes of intraductal papillary mucinous neoplasms (IPMNs) are closely associated with the clinicopathological behavior and recurrence after surgical resection. However, there are no established non-invasive methods to confirm the subtypes of IPMNs without surgery. The aim of this study is to predict the subtypes of IPMNs using the findings of endoscopic ultrasonography (EUS). Methods: Sixty-two consecutive patients with IPMNs who underwent EUS before surgery were retrospectively reviewed. The following EUS findings were analyzed and their relationship with the subtypes was evaluated: diameter of the main pancreatic duct, cyst size, number of cysts, height of mural nodule, early chronic pancreatitis (CP) finding, fatty parenchyma and atrophic parenchyma. Results: The subtypes of IPMNs were as follows: gastric (G)-type 38 (61%), intestinal (I) -type 14 (23%) and pancreatobiliary (PB) -type 10 (16%). Fatty parenchyma was significantly associated with G-type (P < 0.0001). Early CP findings ≥ 2 and atrophic parenchyma were significantly correlated with I-type (P < 0.0001). PB-type was significantly associated with pancreatic parenchyma without early CP findings or fatty degeneration in comparison to the other subtypes (P < 0.0001). Using the above characteristic EUS findings, the sensitivity, specificity, and accuracy were as follows: 63%, 92% and 74%, respectively, in G-type, 57%, 96% and 87% in I-type, and 90%, 94% and 94% in PB-type. Conclusions: The evaluation of EUS findings, especially focused on the pancreatic parenchyma, has the potential to predict the subtypes of IPMN.

Objectives This study aimed to evaluate the pathological features and imaging findings of pancreatic carcinoma in situ (PCIS). Methods Twenty patients with PCIS were categorized as flat (F) (n = 6) and low papillary (LP) (n = 14) types. Results None of F type and 8 (57%) of 14 with LP type lesions showed intraductal infiltrations of the main pancreatic duct (MPD) greater than 10 mm. None of F type and 3 (21%) of 14 with LP type lesions showed skip lesions in the MPD. Magnetic resonance cholangiopancreatography showed irregular MPD stenoses in 5 (83%) of 6 with F and 13 (100%) of 13 with LP type lesions. Magnetic resonance cholangiopancreatography determined that the median lengths of the irregular MPD stenoses were 3.6 mm for F, and 11.6 mm for LP type lesions. Endoscopic retrograde cholangiopancreatography determined that the median lengths of the irregular MPD stenoses were 2.8 mm for F, and 14.3 mm for LP type lesions. Pancreatic cancer recurrences limited to the remnant pancreas occurred in 2 patients with LP type lesions. Conclusions In LP type PCIS, intraductal infiltration of the MPD occurs frequently. There may be multiple lesions, and lesions may recur in the remnant pancreas. Long-term strict follow-up assessments should be implemented for LP type PCIS.

Background: MicroRNA-665 (miR-665), an intracellular inhibitor of pancreatic cancer (PC) cells, might be a potential biomarker to detect pancreatobiliary cancer (PBca). We sought to determine the diagnostic ability of miR-665 as a serum biomarker for PBca, and to explore the role of miR-665 in PC. Methods: This multicenter study enrolled patients with treatment-naïve PBca and healthy participants. PBca-related serum miRNAs were determined using weighted co-expression network analysis of a comprehensive serum miRNA microarray dataset in an exploratory cohort. Using various combinations of PBca-related serum miRNAs, Fisher’s linear discriminant analyses provided miRNA signatures to discriminate PBca from healthy controls. MiRNA signatures with a sensitivity/specificity (SN/SP) of ≥80/80% and high AUC in comparison with the AUC of CA19-9 were defined as the diagnostic miRNA signature in exploratory, validation and independent validation cohorts, whose accuracy was confirmed by 5-fold cross validation. Biology of the diagnostic miRNAs was evaluated using biopsy samples from liver metastasis of PC patients and human PC cells. Results: We analyzed 496 of 1487 enrolled subjects (150 healthy and 134 PBca, 50 healthy and 47 PBca, and 50 healthy and 46 PBca subjects in the exploratory, validation and independent validation cohorts, respectively). Among miRNA signatures from 82 PBca-related miRNAs, a five serum miRNA combination containing miR-665 was identified as the diagnostic miRNA signature in all three cohorts. SN/SP and AUC in the validation and independent validation cohorts were 92/88% and 0.95 (CA19-9: 81/92% and 0.94) and 87/80% and 0.91 (CA19-9: 80/98% and 0.87), respectively. In sub-population analysis for detecting 48 resectable PCs, the discriminative ability of the diagnostic miRNA signature plus CA19-9 (SN/SP: 90/78%) was superior in sensitivity to that of CA19-9 alone (60/94%). In seven PC patients with liver metastasis, high expression of intratumor miR-665 tended to correlate with high serum miR-665 level (r = 0.56) and low expression of intratumor phospho-Erk expression (r = 0.57). Transfection of miR-665 to a human PC cell led to cell growth suppression. Conclusions: This study identified the diagnostic ability of a tumor suppressor miR-665-based serum miRNA signature for PBca. For detecting resectable PC, a miR-665-based serum miRNA signature plus CA19-9 is a superior biomarker to CA19-9 alone. Citation Format: Shuichi Mitsunaga, Makoto Ueno, Masahiro Tsuda, Takamichi Kuwahara, Yukiko Takayama, Keiji Hanada, Hitoshi Yoshida, Kenji Takahashi, Kohei Nakata, Hideaki Iwama, Masafumi Ikeda, Satoshi Kobayashi, Ikuya Miki, Kazuo Hara, Ryota Higuchi, Akinori Shimizu, Tomohiro Nomoto, Hidetaka Iwamoto, Masafumi Nakamura, Etsuro Hatano, Hiroko Sudo, Satoko Takizawa, Atsushi Ochiai. Tumor suppressor miRNA-665 based serum biomarker for detecting pancreatobiliary cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 6686.

Background and aims Endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) is used for the histopathological diagnosis of any type of gastrointestinal disease. Few adverse events are experienced with this procedure; however, the actual rate of adverse events remains unclear. This study aimed to clarify the current status of cases that experienced adverse events related to the EUS-FNA procedure used for histopathologic diagnoses. Methods A retrospective analysis of cases with EUS-FNA-related adverse events in Japanese tertiary centers was conducted by assessing the following clinical data: basic case information, FNA technique, type of procedural adverse events, and prognosis. Results Of the 13,566 EUS-FNA cases overall, the total number of cases in which adverse events related to EUS-FNA occurred was 234. The incidence of EUS-FNA-related adverse events was ~1.7%. Bleeding and pancreatitis cases accounted for ~49.1% and 26.5% of all adverse events, respectively. Bleeding was the most common adverse event with only seven cases requiring blood transfusion. In cases with neuroendocrine tumors, pancreatitis was the most frequent adverse event. Needle tract seeding because of EUS-FNA was observed during the follow-up period in only ~0.1% of cases with pancreatic cancer. There was no mortality because of adverse events caused by EUS-FNA. Conclusions This study revealed that the adverse events-related EUS-FNA for histopathologic diagnoses were not severe conditions, and had low incidence.

ObjectiveStenting is an established endoscopic therapy for malignant gastric outlet obstruction (mGOO). The choice of stent (covered vs uncovered) has been examined in prior randomised studies without clear results.DesignIn a multicentre randomised prospective study, we compared covered (CSEMS) with uncovered self-expandable metal stents (UCSEMS) in patients with mGOO; main outcomes were stent dysfunction and patient survival, with subgroup analyses of patients with extrinsic and intrinsic tumours.ResultsOverall survival was poor with no difference between groups (probability at 3 months 49.7% for covered vs 48.4% for uncovered stents; log-rank for overall survival p=0.26). Within that setting of short survival, the proportion of stent dysfunction was significantly higher for uncovered stents (35.2% vs 23.4%, p=0.01) with significantly shorter time to stent dysfunction. This was mainly relevant for patients with extrinsic tumours (stent dysfunction rates for uncovered stents 35.6% vs 17.5%, pConclusionsDue to poor patient survival, minor differences between covered and uncovered stents may be less relevant even if statistically significant; however, subgroup analysis would suggest to use covered stents for intrinsic and uncovered stents for extrinsic malignancies.

Background Postoperative pancreatic fistula (POPF) is a life-threatening postoperative complication. The aim of this study was to evaluate the efficacy of the fistula risk score (FRS) and preoperative body composition factors for predicting the occurrence of clinically relevant POPF (CR-POPF) after pancreaticoduodenectomy (PD). Methods In this study, 136 consecutive patients who underwent PD between 2006 and 2018 were enrolled. The risk factors of CR-POPF (grades B and C) were analyzed. Preoperative visceral adipose tissue area (VATA), skeletal mass index (SMI), and subcutaneous adipose tissue area (SATA) were calculated from computed tomography data. Results The overall 30-day mortality and morbidity rates were 0.7 and 38%, respectively. The incidence rates of grade B and C CR-POPF were 27 and 4%, respectively. A univariate analysis revealed that male sex, habitual smoking, prognostic nutritional index (PNI) 4 were significantly associated with the incidence of CR-POPF. A multivariate analysis revealed that PNI 4 were the independent risk factors of CR-POPF. Conclusions Preoperative anthropomorphic imbalance, PNI, and FRS were independent risk factors for CR-POPF. Patients with high-risk factors should be closely monitored during the postoperative period.

Objectives The objective of this study was to clarify the role of pancreatectomy for patients with resectable and borderline resectable pancreatic ductal adenocarcinoma aged 80 years or older using a nationwide audit by the Japan Pancreas Society. Methods Data were collected from 39 institutions from 2007 to 2014. The primary endpoint was overall survival, and secondary endpoints were surgical outcomes and predictive factors for prognosis. Results Data were obtained from 556 octogenarians who underwent pancreatectomy (n = 369, 66%), chemo(radio)therapy (n = 99, 18%), and palliative therapy (n = 88, 16%). Median survival times were 20.6, 18.6, and 8.8 months in each group, respectively. Even after propensity score matching, median survival time in the surgery group (22.8 months) was significantly higher than that in the chemotherapy group (18.5 months; hazard ratio, 0.64 [95% confidence interval, 0.44-0.93]; P = 0.020). Significant independent prognostic factors were body mass index, lymph node metastasis, and tumor diameter in the surgery group, and serum albumin level, American Society of Anesthesiologists classification, body mass index, modified Glasgow prognostic score, second-line chemotherapy, and tumor diameter in the chemotherapy group. Conclusions Octogenarians with resectable/borderline resectable pancreatic ductal adenocarcinoma can be recommended for pancreatectomy according to mental and physical fitness for surgical procedures.

Introduction The revised Tokyo guideline 2018 (TG18) recommends early laparoscopic cholecystectomy (LC) in patients with acute cholecystitis (AC) who satisfy the Charlson Comorbidity Index criteria and the ASA Physical Status Classification (ASA-PS). Our study aims to determine the efficacy of the TG18 treatment strategy. Methods We enrolled 324 patients who had been diagnosed with AC according to the TG18 and who underwent cholecystectomy between 2010 and 2018. Perioperative variables and surgical outcomes were analyzed according to the TG18 treatment strategy and severity grading. Results The Charlson Comorbidity Index and ASA-PS scores were significantly higher in patients with Grade II and Grade III AC than in those with Grade I AC. In patients with a higher severity grading, LC failed, necessitating blood transfusion and bailout surgery. Among patients treated by the TG18 strategy were a higher proportion with Grade I or II AC; their ASA-PS scores were significantly lower than patients with Grade III AC. Compared to patients not treated by the TG18 strategy, this group demonstrated significant differences in the achievement of LC, bailout surgery, postoperative hospital stays, and 90-day mortality rates. Intraoperative blood loss and blood transfusion were significantly higher in those not treated by the TG18 strategy. Conclusions Our study shows that the TG18 treatment strategy is well-designed and efficacious. Given the high rate of blood transfusion and conversion surgery in treatment strategies other that TG18, special attention should be paid when selecting the optimal treatment strategy.

OBJECTIVE The aim of the study was to develop a formula for predicting the probability of malignancy of mucinous cystic neoplasm (MCN) of the pancreas with ovarian-type stroma. METHODS A total of 364 patients were enrolled. A total score was calculated as the sum of the approximate integers of the odds ratios of the predictive factors identified by multivariate analysis. The relationship between the total score and pathological results was assessed. RESULTS A total of 321 patients had benign MCN and 43 had malignant MCN. Five possible predictive factors were analyzed: 56 years or older, high serum carcinoembryonic antigen level, high carbohydrate antigen 19-9 level, tumor size of 51 mm or greater, and the presence of mural nodules. The total score was significantly higher in patients with malignant MCN (median, 24; range, 0-37) compared with benign MCN (median, 5; range, 0-33; P < 0.001). Receiver operating characteristic curve analysis demonstrated that the area under the curve was 0.86, and the sensitivity and specificity of the total score for discriminating malignant MCNs were 72% and 83%, respectively, using a cut-off value of 22. CONCLUSIONS The current simple formula can predict the malignancy of MCN and may thus contribute to the adequate management of patients with MCN.

Early diagnosis of pancreatic ductal adenocarcinoma (PDAC) is essential for improving prognosis; however, diagnosing PDAC at an early stage is challenging. In patients with localized high-grade pancreatic intraepithelial neoplasia (HG-PanIN), whose tumorous lesion is undetectable on cross-sectional images such as computed tomography or magnetic resonance image, long-term survival is expected. Pancreatic cystic lesions or main pancreatic duct (MPD) dilatation are important indirect findings for the initial diagnosis of HG-PanIN. Magnetic resonance cholangiopancreatography (MRCP) and endoscopic ultrasound (EUS) should play important roles in detecting abnormal image findings, such as local irregular MPD stenosis, caliber MPD changes, small cystic lesions, or branch duct dilatation. Additionally, EUS could detect hypoechoic areas around the MPD stenosis in some patients with HG-PanIN. Subsequently, endoscopic retrograde cholangiopancreatography (ERCP) and its associated pancreatic juice cytology, including serial pancreatic juice aspiration cytologic examination (SPACE) after placement of an endoscopic nasopancreatic drainage (ENPD) tube, may have high diagnostic accuracy for confirming the malignancy in HG-PanIN. Although ERCP and its associated pancreatic cytology, including SPACE, may be associated with post-ERCP pancreatitis (PEP), a recent randomized trial suggested that a 4-Fr ENPD tube may reduce the incidence of PEP. In the future, further prospective multicenter studies are required to establish a standard method of SPACE. Additionally, further studies for novel biomarkers could help to establish evolutionary methods with duodenal fluid and pancreatic juice for the early and accurate diagnosis of early-stage PDAC.

Introduction Adenoma and intra-adenoma carcinoma of the gallbladder are relatively rare diseases, and the World Health Organization classification reports a frequency of 0.3% for gallbladder adenomas. Precise preoperative diagnosis of gallbladder cancer, especially in the early stages, is challenging. Herein, we report a case of pyloric adenomatous carcinoma of the gallbladder, diagnosed by laparoscopic cholecystectomy and pathology, along with a literature review. This case was reported in accordance with the SCARE 2020 Guideline (Ref). Presentation of case A 62-year-old woman was diagnosed with a 4-mm polypoid lesion in the gallbladder during a medical examination. The patient was followed-up by ultrasonography (US) once a year and was referred to our department because of an increase in size. Carcinoembryonic antigen and carbohydrate antigen 19-9 levels were within normal limits. Abdominal ultrasonography revealed a pedunculated polypoid lesion in the body of the gallbladder measuring 8 mm. Computed tomography demonstrated that the whole tumor was enhanced in the early phase without significant lymph node enlargement. Magnetic resonance cholangiopancreatography demonstrated a type Ip polypoid lesion located in the body of the gallbladder without pancreaticobiliary junctional abnormalities. Endoscopic ultrasound detected a superficial nodular-type Ip polypoid lesion in the gallbladder body with a parenchyma-like internal echogenic pattern. Discussion Based on these findings, the patient was diagnosed with gallbladder adenoma, and laparoscopic cholecystectomy was performed. Histopathological examination revealed the tumor was a papillary growth of atypical high columnar epithelial cells. The final diagnosis was pyloric adenoma with high-grade dysplasia and intra-adenoma carcinoma. The patient is currently undergoing outpatient follow-up without recurrence for 1 year. Conclusion Early gallbladder carcinoma with adenoma should be considered in patients with small gallbladder polypoid lesions. Considering the surgical stress of cholecystectomy and the malignant potential of gallbladder cancer, preceding surgery would be acceptable., Highlights • Incidental gallbladder cancer is rare and preoperative assessment of GBPL is important. • Considering the malignant potential of GBC, preceding surgery would be acceptable.

Objectives This study aimed to investigate the utility of fluorodeoxyglucose (FDG) positron emission tomography for solid pseudopapillary neoplasm (SPN) diagnosis. Methods The subjects included 53 cases of SPN. We compared the maximal standardized uptake volume (SUVmax) with those of 25 cases of pancreatic duct cancer and 18 cases of pancreatic neuroendocrine neoplasm. In addition, immunopathological testing for SPN with regard to FDG uptake was undertaken. Results An increase in SUVmax was observed in all tumors with increased tumor diameter. Among tumors of 20 mm or smaller, the SUVmax of SPN was significantly higher than those of pancreatic duct cancer and pancreatic neuroendocrine neoplasm. The results of a pathological study of FDG uptake in SPN revealed increased glucose transporter protein type 1 expression with tumor enlargement. Furthermore, increased hypoxia-inducible factor-1 and vascular endothelial growth factor expression under hypoxic conditions were observed in the areas of necrosis. Conclusions In cases in which high FDG uptake is observed in small pancreatic tumors, FDG positron emission tomography is potentially useful for SPN differentiation. The factors involved in FDG uptake in SPN include cell density and glucose transporter protein expression, as well as hypoxia-inducible factor and vascular endothelia growth factor expression in the hypoxic environment of necrotic areas.

Chronic pancreatitis (CP) is a fibro-inflammatory disease of the pancreas. Early diagnosis and intervention, before CP becomes established and irreversible, are essential to improve the long-term outcomes. The world’s first diagnostic criteria for early CP were proposed in Japan in 2009, but their clinical utility remains elusive. This study aimed to clarify whether patients with early CP progress to definite CP. This is a multicenter, prospective study. Patients diagnosed as having early CP according to the Japanese diagnostic criteria were prospectively followed for 2 years. Clinical profiles including symptoms, drinking and smoking status, laboratory data, imaging findings and treatments were analyzed. Among the 83 patients who completed the 2-year follow-up period, four (4.8%) patients progressed to definite CP. The diagnosis of 48 (57.8%) patients was unchanged, and that of 31 (37.3%) patients was downgraded. All the four progressive patients were male, alcohol-related, smokers (3 current and 1 ever), and continued drinking. Comparison of the clinical profiles between the progression group (n = 4) and non-progression group (n = 79) revealed that etiology (alcohol-related), smoking status and presence of acute pancreatitis episodes were associated with the progression to definite CP. The Japanese diagnostic criteria could identify some patients before the progression to definite CP, while the majority of the patients did not progress. Trial registration number: UMIN000015992.