Potential of Carbohydrate Antigen 19-9 and Serum Apolipoprotein A2-Isoforms in the Diagnosis of Stage 0 and IA Pancreatic Cancer.

Apolipoprotein A2-ATQ/AT (apoA2-ATQ/AT) is a new biomarker for diagnosing pancreatic cancer (PC). In this study, the value of blood carbohydrate antigen 19-9 (CA19-9) and apoA2-ATQ/AT levels in diagnosing stage 0 and IA PC was evaluated. During 2014-2021, 12 patients with stage 0 PC and 12 patients with IA PC (average age: 73.8 years) underwent resection at JA Onomichi General Hospital. In addition, the data of 200 healthy controls were collected from a community-based cohort study. Levels of two apoA2-isoforms were measured using enzyme-linked immunosorbent assay (ELISA) with specific antibodies to calculate the apoA2-i Index as a surrogate value for apoA2-ATQ/AT. The cutoff value for the apoA2-i Index was determined to be 62.9 µg/mL. CA19-9 levels were also measured through ELISA. Among all 24 patients with PC, the positivity rates for apoA2-i and CA19-9 were 33.3% and 25.0%, respectively. The positivity rates for apoA2-i and CA19-9 were 16.7% and 8.3% in patients with stage 0 PC and 50.0% and 41.7% in those with stage IA, respectively. For CA19-9-negative patients, the apoA2-i positivity rate was 9.1% in stage 0 and 42.9% in stage IA. The combined positivity rate for both markers was 16.7% in stage 0 and 66.7% in stage IA. Imaging findings in apoA2-i- and CA19-9-positive patients included pancreatic duct dilatation (87.5%/100%), duct stenosis (75.0%/50%), and atrophy (87.5%/66.7%). The imaging findings of this study suggest that apoA2-i may enhance the sensitivity for detecting CA19-9-negative stage 0 and IA PC, and complementary measurements with CA19-9 may be valuable for diagnosing early-stage PC. Therefore, minute PC with pancreatic duct dilation, duct stenosis, and atrophy may exhibit a high positivity rate, aiding differential diagnosis.

Is multidisciplinary treatment effective for invasive intraductal papillary mucinous carcinoma?

Background: Surgical resection is standard treatment for invasive intraductal papillary mucinous carcinoma (IPMC); however, impact of multidisciplinary treatment on survival including postoperative adjuvant therapy (AT), neoadjuvant therapy (NAT), and treatment for recurrent lesions is unclear. We investigated the effectiveness of multidisciplinary treatment in prolonging survival of patients with invasive IPMC. Methods: This retrospective multi-institutional study included 1183 patients with invasive IPMC undergoing surgery at 40 academic institutions. We analyzed the effects of AT, NAT, and treatment for recurrence on survival of patients with invasive IPMC. Results: Completion of the planned postoperative AT for 6 months improved the overall survival (OS), disease-specific survival (DSS), and recurrence-free survival (RFS) of patients with stage IIB and stage III resected invasive IPMC, elevated preoperative carbohydrate antigen 19-9 level, lymphovascular invasion, perineural invasion, serosal invasion, and lymph node metastasis on un-matched and matched analyses. Of the patients with borderline resectable (BR) invasive IPMC, the OS (p = 0.001), DSS (p = 0.001), and RFS (p = 0.001) of patients undergoing NAT was longer than that of those without on the matched analysis. Of the 484 invasive IPMC patients (40.9%) who developed recurrence after surgery, the OS of 365 patients who received any treatment for recurrence was longer than that of those without treatment (40.6 vs. 22.4 months, p < 0.001). Conclusion: Postoperative AT might benefit selected patients with invasive IPMC, especially those at high risk of poor survival. NAT might improve the survivability of BR invasive IPMC. Any treatment for recurrence after surgery for invasive IPMC might improve survival.

Endoscopic Retrograde Cholangiopancreatography-Related Procedures for the Differential Diagnosis of Isolated Immunoglobin G4-Related Sclerosing Cholangitis and Perihilar Cholangiocarcinoma.

BACKGROUND/PURPOSE: Differential diagnosis of isolated immunoglobin (Ig)G4-related sclerosing cholangitis (IgG4-SC) and cholangiocarcinoma is challenging. We aimed to clarify the role of endoscopic retrograde cholangiography (ERCP)-related procedures in the differential diagnosis of isolated IgG4-SC and perihilar cholangiocarcinoma (PHCC). METHODS: Seven patients with hilar-type isolated IgG4-SC diagnosed at Hiroshima University Hospital and sixty-five patients with surgically resected invasive PHCC were enrolled, and the diagnostic yields of intraductal ultrasonography (IDUS), peroral cholangioscopy (POCS), and pathological examinations were determined. RESULTS: In six of seven (86%) patients with isolated IgG4-SC, the stricture was in the perihilar bile duct. IDUS showed that symmetrical wall thickening (40% vs. 5%, p = 0.04), homogeneous internal echo (80% vs. 5%, p < 0.001), and smooth outer margins (80% vs. 6%, p < 0.001) were more frequent in isolated IgG4-SC than in PHCC. POCS showed a smooth mucosal surface more frequent in isolated IgG4-SC (75% vs. 7%, p = 0.006). Only one patient had two pathological findings characteristic of IgG4-SC. The sensitivity for diagnosing PHCC was 81% using two or more combined sampling methods. CONCLUSIONS: Pathological examinations have limitations in the differential diagnosis of isolated-IgG4-SC and PHCC, and a diagnostic strategy that combines multiple ERCP-related procedures, including IDUS and POCS, is recommended.

Prospective multicenter surveillance study of branch-duct intraductal papillary mucinous neoplasm of the pancreas; risk of dual carcinogenesis.

BACKGROUND: The natural history of branch-duct intraductal papillary mucinous cystic neoplasms (BD-IPMNs) in the pancreas remains unclear. This study aimed to answer this clinical question by focusing on the development of concomitant pancreatic ductal adenocarcinomas (cPDAC). METHODS: The Japan Pancreas Society conducted a prospective multicenter surveillance study of BD-IPMN every six months for five years. The primary endpoints were progression of BD-IPMN, progression to high-grade dysplasia/invasive carcinoma (HGD/IC), and cPDAC. Factors predicting the progression of BD-IPMN to HGD/IC and development of cPDAC were also assessed as secondary endpoints. RESULTS: Among the 2104 non-operated patients, 348 (16.5 %) showed progression of primary BD-IPMN. Cumulative incidences of BD-IPMN with HGD/IC and cPDAC during the 5.17-year surveillance period were 1.90 % and 2.11 %, respectively, and standard incidence ratios of BD-IPMN with HGD/IC and cPDAC were 5.28 and 5.73, respectively. Of 38 cPDACs diagnosed during surveillance, 25 (65.8 %) were resectable. The significant predictive characteristics of BD-IPMN for progression to HGD/IC were larger cyst size (p = 0.03), larger main pancreatic duct size (p < 0.01), and mural nodules (p = 0.02). Significant predictive characteristics for the development of cPDAC were male sex (p = 0.03) and older age (p = 0.02), while the size of IPMN was not significant. CONCLUSION: Careful attention should be given to "dual carcinogenesis" during BD-IPMN surveillance, indicating the progression of BD-IPMN to HGD/IC and development of cPDAC distinct from BD-IPMN, although the establishment of risk factors that predict cPDAC development remains a challenge (UMIN000007349).

Factors Affecting Nonfunctioning Small Pancreatic Neuroendocrine Neoplasms and Proposed New Treatment Strategies.

BACKGROUND & AIMS: Despite previously reported treatment strategies for nonfunctioning small (≤20 mm) pancreatic neuroendocrine neoplasms (pNENs), uncertainties persist. We aimed to evaluate the surgically resected cases of nonfunctioning small pNENs (NF-spNENs) in a large Japanese cohort to elucidate an optimal treatment strategy for NF-spNENs. METHODS: In this Japanese multicenter study, data were retrospectively collected from patients who underwent pancreatectomy between January 1996 and December 2019, were pathologically diagnosed with pNEN, and were treated according to the World Health Organization 2019 classification. Overall, 1490 patients met the eligibility criteria, and 1014 were included in the analysis cohort. RESULTS: In the analysis cohort, 606 patients (59.8%) had NF-spNENs, with 82% classified as grade 1 (NET-G1) and 18% as grade 2 (NET-G2) or higher. The incidence of lymph node metastasis (N1) by grade was significantly higher in NET-G2 (G1: 3.1% vs G2: 15.0%). Independent factors contributing to N1 were NET-G2 or higher and tumor diameter ≥15 mm. The predictive ability of tumor size for N1 was high. Independent factors contributing to recurrence included multiple lesions, NET-G2 or higher, tumor diameter ≥15 mm, and N1. However, the independent factor contributing to survival was tumor grade (NET-G2 or higher). The appropriate timing for surgical resection of NET-G1 and NET-G2 or higher was when tumors were >20 and >10 mm, respectively. For neoplasms with unknown preoperative grades, tumor size >15 mm was considered appropriate. CONCLUSIONS: NF-spNENs are heterogeneous with varying levels of malignancy. Therefore, treatment strategies based on tumor size alone can be unreliable; personalized treatment strategies that consider tumor grading are preferable.

Prognostic Factors for Severe-to-Fatal Post-Endoscopic Retrograde Cholangiopancreatography Pancreatitis: A Multicenter Prospective Cohort Study.

The prognostic factors associated with severe-to-fatal post-endoscopic retrograde cholangiopancreatography (ERCP) pancreatitis (PEP) remain unclear despite the extensive number of studies on PEP. In total, 3739 ERCP patients with biliary disease with an intact papilla and indicated for ERCP were prospectively enrolled at 36 centers from April 2017 to March 2018. Those with acute pancreatitis diagnosed before ERCP, altered gastrointestinal anatomy, and an American Society of Anesthesiologists (ASA) physical status > 4 were excluded. Univariate and multivariate logistic regression analyses were performed on patient-related factors, operator-related factors, procedure-related factors, and preventive measures to identify potential prognostic factors for severe-to-fatal PEP. Multivariate analyses revealed pancreatic guidewire-assisted biliary cannulation (OR 13.59, 95% CI 4.21-43.83, p < 0.001), post-ERCP non-steroidal anti-inflammatory drug (NSAID) administration (OR 11.54, 95% CI 3.83-34.81, p < 0.001), and previous pancreatitis (OR 6.94, 95% CI 1.45-33.33, p = 0.015) as significant risk factors for severe-to-fatal PEP. Preventive measures included endoscopic biliary sphincterotomy (EST; OR 0.29, 95% CI, 0.11-0.79, p = 0.015) and prophylactic pancreatic stents (PPSs; OR 0.11, 95% CI, 0.01-0.87, p = 0.036). In biliary ERCP, pancreatic guidewire-assisted biliary cannulation, NSAID administration after ERCP, and previous pancreatitis were risk factors for severe-to-fatal PEP, whereas EST and PPS were significant preventive measures for severe-to-fatal PEP.

Is preoperative pancreatic juice cytology useful for determining therapeutic strategies for patients with intraductal papillary mucinous neoplasm of the pancreas?

BACKGROUND: We compared the results of preoperative pancreatic juice cytology (PJC) and final pathological diagnosis after resection in patients who underwent resection of intraductal papillary mucinous neoplasm (IPMN) of the pancreas to determine whether preoperative PJC can help determine therapeutic strategies. METHODS: Of 1130 patients who underwent surgical resection IPMN at 11 Japanese tertiary institutions, the study included 852 patients who underwent preoperative PJC guided by endoscopic retrograde cholangiopancreatography (ERCP). RESULTS: The accuracy of preoperative PJC for differentiation between cancerous and noncancerous lesions were 55% for IPMN overall; 59% for the branch duct type; 49% for the main pancreatic duct type; 53% for the mixed type, respectively. On classifying IPMN according to the diameters of the mural nodule (MN) and main pancreatic duct (MPD), the corresponding values for diagnostic performance were 40% for type 1 (MN ≥5 mm and MPD ≥ 10 mm); 46% for type 2 (MN ≥5 mm and MPD < 10 mm); 61% for type 3 (MN < 5 mm and MPD ≥ 10 mm); 72% for type 4 (MN < 5 mm and MPD < 10 mm), respectively. CONCLUSIONS: PJC in IPMN is not a recommended examination because of its low overall sensitivity and no significant difference in diagnostic performance by type, location, or subclassification. Although the sensitivity is low, the positive predictive value is high, so we suggest that pancreatic juice cytology be performed only in cases where the patient is not sure about surgery.

Feasibility of Surveillance for Mucinous Cystic Neoplasm of the Pancreas: A Multi-Institutional Retrospective Study of 328 Patients by the Japanese Pancreatic Society.

OBJECTIVE: We aimed to elucidate the feasibility of surveillance of patients with mucinous cystic neoplasm (MCN). METHODS: We performed a retrospective, multi-institutional study of 328 patients who underwent surgery for MCN at 18 Japanese institutions. Patients with MCN were divided into an immediate surgery group and a surveillance group, which underwent surgery after surveillance. RESULTS: The median surveillance period until surgery in the surveillance group was 27 months (range, 7-165 months). Compared with the immediate surgery group, the surveillance group showed smaller tumor diameter (46 vs 50 mm, P = 0.01), more frequent laparoscopic approach (58% vs 37%, P < 0.01), and less frequent malignancy (7% vs 15%, P = 0.03). The new appearance of mural nodules and elevation of serum tumor markers were associated with malignancy in the surveillance group. Two patients in the surveillance group experienced postoperative recurrence, although there was no significant difference in recurrence or disease-free survival between the two groups. In the surveillance group, the 1-, 5-, and 10-year cumulative incidence rates of malignant MCN were 0.8%, 5.6%, and 36.5%, respectively. CONCLUSION: As the risk of progression to malignant MCNs increases over the long term, MCNs should be resected rather than subjected to unnecessary surveillance.

Relapse rate and predictors of relapse after cessation of glucocorticoid maintenance therapy in type 1 autoimmune pancreatitis: a multicenter retrospective study.

BACKGROUND: Type 1 autoimmune pancreatitis responds well to glucocorticoid therapy with a high remission rate. Moreover, glucocorticoid maintenance therapy can help prevent relapse. However, the relapse rate following cessation of long-term glucocorticoid therapy is unknown. The aim of this study was to clarify the relapse rate and predictors of relapse following long-term glucocorticoid therapy cessation. METHODS: We analyzed 94 patients who achieved remission after undergoing glucocorticoid therapy, discontinued treatment after at least 6 months of maintenance therapy, and were subsequently followed up for at least 6 months. The patients were divided into three groups based on treatment duration (< 18, 18-36, and ≥ 36 months), and their relapse rates were compared. Univariate and multivariate analyses of clinical factors were conducted to identify relapse predictors. RESULTS: After discontinuing glucocorticoid therapy, relapse was observed in 43 (45.7%) patients, with cumulative relapse rates of 28.2% at 1 year, 42.1% at 3 years, 47.0% at 5 years, and a plateau of 77.6% at 9 years. Of the 43 patients who relapsed, 25 (58.1%) relapsed within 1 year after after cessation of glucocorticoid therapy. Relapse and cumulative relapse rates did not differ significantly according to treatment duration. In the multivariate analysis, an elevated serum IgG4 level at the time of glucocorticoid cessation was found to be an independent predictor of relapse (hazard ratio, 4.511; p < 0.001). CONCLUSIONS: A high relapse rate occurred after cessation of glucocorticoid maintenance therapy, regardless of the duration of maintenance therapy, especially within the first year after cessation. However, the normalization of long-term serum IgG4 levels may be a factor in considering cessation.

Diagnostic Ability and Safety of Repeated Pancreatic Juice Cytology Using an Endoscopic Nasopancreatic Drainage Catheter for Pancreatic Ductal Adenocarcinoma: A Multicenter Prospective Study.

Pathological examination is essential for the diagnosis and treatment of pancreatic ductal adenocarcinoma (PDAC). Moreover, a reliable pathological diagnosis is extremely important for improving prognosis, especially in early-stage PDAC. This study prospectively evaluated the usefulness of repeated pancreatic juice cytology (PJC) using an endoscopic nasopancreatic drainage (ENPD) catheter for the diagnosis of PDAC. We enrolled 82 patients suspected of having resectable PDAC, based on imaging studies, and judged the necessity for cytology. The diagnostic yield of up to six repeated PJCs and the incidence of complications, such as pancreatitis, was evaluated. A total of 60 patients were diagnosed with PDAC. The overall sensitivity and specificity were 46.7% and 95.5%, respectively. The cumulative positivity rate increased with the number of sampling sessions, reaching 58.3% in the sixth session. The sensitivity was significantly higher in the pancreatic head than in the pancreatic tail (p = 0.043). Additionally, it was 100% in four patients with a tumor size ≤10 mm. Pancreatitis occurred in six patients (7.3%), all of whom were treated conservatively. In the diagnosis of PDAC, repeated PJC using an ENPD catheter revealed a cumulative effect of sensitivity up to six times and an excellent diagnostic yield for small PDAC.

A case of frequent hypoglycemic attacks successfully controlled with capecitabine plus temozolomide and 177Lu-DOTATATE peptide receptor radionuclide therapy in a patient with recurrent pancreatic insulinoma.

A 59-year-old woman with metastatic pancreatic insulinoma, having undergone several treatment regimens including sunitinib, everolimus, lanreotide and streptozocin plus 5-fluorouracil, was admitted to our hospital because of frequent hypoglycemic attacks. These were refractory to medical treatment using diazoxide and required frequent daily intravenous glucose infusions. She was started on capecitabine and temozolomide (CAPTEM), followed by initiation of 177Lu-DOTATATE peptide receptor radionuclide therapy (PRRT). The frequency of hypoglycemic attacks decreased after treatment began and she was discharged on day 58 post-admission, without requiring daily glucose infusions. CAPTEM and PRRT were continued without any major adverse events. Computed tomography revealed shrinkage of primary and metastatic lesions, an anti-tumor effect that continued 8 months after treatment was initiated. Hypoglycemic attacks caused by insulinomas are often refractory to conventional therapy; however, combination treatment using CAPTEM and PRRT has demonstrated a positive and significant response, successfully restoring glycemic control.

A comparative study between computed tomography and endoscopic ultrasound in the detection of a mural nodule in intraductal papillary mucinous neoplasm -Multicenter observational study in Japan.

BACKGROUND/OBJECTIVES: The detection of malignancy is a major concern in the management of intraductal papillary mucinous neoplasm (IPMN). The height of the mural nodule (MN), estimated using endoscopic ultrasound (EUS) and computed tomography (CT), has been considered crucial for predicting malignant IPMN. Currently, whether surveillance using CT or EUS alone is sufficient for detecting MNs remains unclear. This study aimed to compare the ability of CT and EUS to detect MNs in IPMN. METHODS: This multicenter, retrospective observational study was conducted in 11 Japanese tertiary institutions. Patients who underwent surgical resection of IPMN with MN after CT and EUS examinations were eligible to participate. The MN detection rates between CT and EUS were examined. RESULTS: Two-hundred-and-forty patients who underwent preoperative EUS and CT had pathologically confirmed MNs. The MN detection rates of EUS and CT were 83% and 53%, respectively (p < 0.001). Additionally, the MN detection rate of EUS was significantly higher than that of CT regardless of morphological type (76% vs. 47% in branch-duct-type IPMN; 90% vs. 54% in mixed IPMN; 98% vs. 56% in main-duct-type IPMN; p < 0.001). Further, pathologically confirmed MNs ≥5 mm were more frequently observed on EUS than on CT (95% vs. 76%, p < 0.001). CONCLUSIONS: EUS was superior to CT for the detection of MN in IPMN. EUS surveillance is essential for the detection of MNs.

Clinical Practice Guidelines for Pancreatic Cancer 2022 from the Japan Pancreas Society: a synopsis.

OBJECTIVES: Clinical Practice Guidelines for Pancreatic Cancer was first published in 2006 by the Japan Pancreas Society, and revised in 2009, 2013, 2016, and 2019. In July 2022, Clinical Practice Guidelines for Pancreatic Cancer was newly revised in Japanese. METHODS: For this revision, we developed an entirely new guideline according to the Minds Manual for Guideline Development 2020, which includes the concepts of GRADE-Grading Recommendations Assessment, Development, and Evaluation, to enable a better understanding of the current guidelines. Patients and the public were actively involved in both the development and implementation of the guideline. RESULTS: The guideline includes algorithms for diagnosis, treatment, chemotherapy, and precision medicine of pancreatic cancer, and addresses 7 subjects: diagnosis, surgical therapy, adjuvant therapy, radiation therapy, chemotherapy, stent therapy, and supportive & palliative medical care. It includes 73 clinical questions and 112 statements. The statements correspond to the clinical questions, evidence levels, recommendation strengths, and agreement rates. CONCLUSIONS: This guideline represents the most standard clinical and practical management guideline available until date in Japan. This is the English synopsis of the Clinical Practice Guidelines for Pancreatic Cancer 2022 in Japanese, and is an attempt to disseminate the Japanese guideline worldwide to introduce the Japanese approach to the clinical management of pancreatic cancer.

Curative surgery for primary squamous cell carcinoma of the liver: a rare case study.

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 T1-weighted magnetic resonance imaging (MRI) and high signal on T2-weighted MRI. The cytology of bile juice showed no malignant findings. Endoscopic ultrasound-guided fine-needle aspiration biopsy was performed, which was suggestive of primary hepatic SCC. Tumor markers cytokeratin 19 fragment (CYFRA) and SCC-related antigen were elevated, at 25.2 ng/mL and 14.7 ng/mL, respectively. Left lobectomy and hilar lymph node dissection were performed. One month after surgery, the tumor marker values showed a marked decrease of 1.8 ng/mL for CYFRA and 0.3 ng/dL for SCC-related antigen. The patient has been without recurrence for more than one and half year postoperatively. SCC-related antigen and CYFRA were markedly decreased after tumor resection in this case, which may suggest their utility as tumor markers for SCC of liver origin.

Acute necrotic disorder of the small intestine post-coronavirus disease-2019 vaccination.

The Pfizer-BioNTech coronavirus disease 2019 (COVID-19) vaccine is extensively used worldwide, and its safety has been proven. Herein, we report a case of an acute necrotic disorder in the small intestine post-COVID-19 vaccination. The patient developed severe abdominal pain the day after the first vaccination. Contrast-enhanced computed tomography showed extensive ileum wall thickening and ascites. Colonoscopy revealed a ring-shaped ulcer and stricture in the terminal ileum. Ileocecal resection was performed, and the patient did not have further episodes of a necrotic disorder in the small intestine. Although it is unknown if this event is associated with vaccination, and this occurrence also does not outweigh the efficacy and safety of the Pfizer-BioNTech COVID-19 vaccine, gastroenterologists need to be aware of this rare case, given its noteworthy timing.

Efficacy of bailout surgery for preventing intraoperative biliary injury in acute cholecystitis.

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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.

Delayed local recurrence of pancreatic adenosquamous cell carcinoma after curative surgery: A case report.

INTRODUCTION: Pancreatic adenosquamous cell carcinoma (PASC) is a rare histological type of pancreatic malignancy with a particularly poor prognosis, even after curative surgery. Here, we describe the long-term prognosis of PASC in a patient who developed delayed local recurrence of the remnant pancreas after successful distal pancreatectomy, together with a literature review. PRESENTATION OF CASE: A 59-year-old woman had a history of hepatitis C. Computed tomography revealed a hypointense mass in the pancreatic body in the arterial phase of the study. Magnetic resonance imaging revealed a tumor (20 mm) in the pancreatic body and dilatation of the main pancreatic duct at the periphery of the tumor. The patient was diagnosed with resectable pancreatic ductal adenocarcinoma and underwent distal pancreatectomy with lymphadenectomy; her postoperative course was uneventful. Immunohistochemical analysis of the resected specimen confirmed the diagnosis of tumor node metastasis [TNM] classification T2N1M0 stage IIB. Five years after curative surgery, following adjuvant systemic chemotherapy with S-1, local recurrence in the remnant pancreas occurred, which invaded the common hepatic artery and celiac pleural plexus. Systemic chemotherapy with gemcitabine and abraxiane is currently underway. DISCUSSION: Curative surgery significantly affects the prognosis of patients with PASC. Adjuvant chemotherapy may prolong the survival of these patients. Delayed remnant pancreatic recurrence should be considered during the surveillance of pancreatic cancer after curative resection. CONCLUSION: We present a case of PASC in a patient who developed local recurrence in the remnant pancreas 5 years after successful distal pancreatectomy. Special attention should be paid not only to early recurrence but also to delayed local recurrence in PASC.

Pancreatic hamartoma: detection of harbouring NAB2::STAT6 fusion gene.

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.

Repeat pancreatic resection for metachronous pancreatic metastasis from renal cell carcinoma: A case report.

BACKGROUND: Pancreatic metastasis (PM) from renal cell carcinoma (RCC) is relatively rare. Surgical resection of PM from RCC is considered as the first choice treatment for achieving long-term prognosis. Herein, we report a case of secondary multiple metastases from RCC to the remnant pancreas following pancreatectomy, with a review of the relevant literature. PRESENTATION OF CASE: A 69-year-old man who underwent left nephrectomy for RCC (T2N0M0, stage II) 12 years ago was referred to our hospital. Multiple metastases to the pancreatic head from RCC occurred 2 years after the primary surgery, for which pancreaticoduodenectomy was performed. Nine years after metastatic resection, multiple tumors of the remnant pancreas were detected on dynamic computed tomography (CT); all tumors showed strong enhancement in the early phase, which persisted into the late phase. The tumors were round, the maximum diameter of the tumor was 20 mm, and they were hyperintense on T2-weighted magnetic resonance imaging. Positron emission tomography-CT revealed slight fluorodeoxyglucose uptake in the tumor. Multiple PMs were diagnosed, and the remnant pancreas was completely resected. Two years later, the patient was alive and showed no recurrence. CONCLUSIONS: Surgical resection could provide long-term prognosis, even if secondary PM from RCC occurs metachronously. Long-term follow-up is recommended after primary resection, and vigilance regarding the occurrence of PM is needed.

Endoscopic approach in the diagnosis of high-grade pancreatic intraepithelial neoplasia.

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.