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酒井 新医学部附属病院 消化器内科助教
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- OBJECTIVES: Covered self-expandable metal stents are commonly used for unresectable malignant distal biliary obstruction. Partially covered self-expandable metal stents have uncovered sections at both ends; however, their anti-migration effect remains unclear. The objective of this study was to evaluate that effect by comparing such stents with fully covered self-expandable metal stents for patients with unresectable malignant distal biliary obstruction. METHODS: This was a multicenter, retrospective comparative study of partially covered stents with fully covered stents for unresectable malignant distal biliary obstruction. Stent migration, recurrent biliary obstruction, and the time to recurrent biliary obstruction were compared between them. RESULTS: Thirty-nine patients with partially covered stents were included and compared with 42 patients with fully covered stents. The partially covered group had a significantly lower stent migration rate (3% vs. 36%; p < 0.001). The recurrent biliary obstruction rate was significantly lower in the partially covered group (21% vs. 43%; p = 0.036). The non-recurrent biliary obstruction rate at 6 months was 90% and 68% in the partially and fully covered groups, respectively. The time to recurrent biliary obstruction was significantly longer in the partially covered group (Gray's test, p = 0.016). Only partially covered stent placement was significantly associated with a lower risk of stent migration (subdistribution hazard ratio = 0.077; 95% confidence interval = 0.01-0.60; p = 0.014) in the multivariable analysis. CONCLUSIONS: The anti-migration effect of partially covered self-expandable metal stents was associated with a reduced recurrence of biliary obstruction and prolonged time to such obstruction.2025年04月, DEN open, 5(1) (1), e70100, 英語, 国際誌研究論文（学術雑誌）
- BACKGROUND AND AIMS: Endoscopic ultrasound (EUS)-guided transmural drainage with on-demand endoscopic necrosectomy (EN) is increasingly utilized to manage walled-off necrosis (WON). It has not been fully elucidated how EN and its timing are correlated with treatment outcomes compared to the drainage-based approach. METHODS: Within a multi-institutional cohort of 423 patients with pancreatic fluid collections including 227 patients with WON, we identified 153 patients who received the step-up treatment following the initial EUS-guided drainage of symptomatic WON, including 102 EN patients and 51 non-EN (drainage) patients. Using the competing-risks multivariable proportional hazards regression model with adjustment for potential confounders, we calculated subdistribution hazard ratios (SHRs) for clinical treatment success (WON resolution) by the use of EN and its timing. RESULTS: Compared to drainage alone, the EN-based treatment was associated with a shorter time to clinical success with a multivariable SHR of 1.66 (95% confidence interval, 1.12-2.46). Despite a higher risk of procedure-related bleeding in the EN group, there were no differences in the rates of severe adverse events (7.8% vs. 5.9% in the EN and non-EN groups, respectively) and mortality (6.9% vs. 9.8%). In the EN-treated patients, the timing of EN was not statistically significantly associated with the time to clinical success (Ptrend = 0.34) CONCLUSION: Among patients receiving EUS-guided treatment of symptomatic WON, the use of EN in addition to drainage procedures was associated with earlier disease resolution. Further research is desired to determine the optimal timing of initiating EN considering a risk-benefit balance and cost-effectiveness.2024年11月, Gastrointestinal endoscopy, 英語, 国際誌研究論文（学術雑誌）
- (一社)日本癌学会, 2024年09月, 日本癌学会総会記事, 83回, J - 2054, 英語膵癌の腫瘍免疫・予後に関連する腫瘍内細菌叢の探索(Association of Intratumoral Microbiome with Tumor Immunity and Prognosis in Human Pancreatic Cancer)
- Background Pancreatic duct (PD) disruption can occasionally be attributed to pancreatic cancer. Therapeutic interventions for PD disruption due to pancreatic cancer and their influence on pancreatic cancer prognosis remain unclear. This study investigated the therapeutic modalities and prognostic implications of PD disruption in pancreatic cancer. Methods This retrospective study included 15 patients with PD disruption concomitant with pancreatic cancer between April 2011 and March 2023. As an endoscopic intervention for PD disruption, endoscopic pancreatic stenting (EPS) or endoscopic ultrasonography-guided pancreatic fluid collection drainage (EUS-PFD) was performed. Technical success was defined as stent placement and clinical success was defined as an improvement in PD disruption. Results Of the 15 cases of PD disruption, two involved only pancreatic juice leakage without symptoms, four involved pancreatic pseudocyst (PPC) without infection, and nine involved PPC with infection. Four patients underwent EPS, nine underwent EUS-PFD, and two underwent lumen-apposing metal stent placement. All patients achieved both technical and clinical success without complications. The clinical stage of pancreatic cancer ranged from carcinoma in situ to the metastatic phase. For the treatment of pancreatic cancer, five patients underwent surgical resection, and eight underwent chemotherapy. There was no obvious recurrence of peritoneal sowing. The median overall survival from the diagnosis of pancreatic cancer in the resected and non-resected cases was 74 and 9.6 months, respectively. Conclusion Endoscopic intervention was effective in all cases of PD disruption due to pancreatic cancer. Furthermore, even in cases of pancreatic cancer after PD disruption, survival rates were similar to those in cases without PD disruption and were achieved through surgical resection or chemotherapy.2024年08月, Cureus, 16(8) (8), e67482, 英語, 国際誌研究論文（学術雑誌）
- (一社)日本膵臓学会, 2024年07月, 膵臓, 39(3) (3), A199 - A199, 日本語
- (一社)日本膵臓学会, 2024年07月, 膵臓, 39(3) (3), A206 - A206, 日本語
- (一社)日本膵臓学会, 2024年07月, 膵臓, 39(3) (3), A336 - A336, 日本語
- (一社)日本消化器内視鏡学会, 2024年04月, Gastroenterological Endoscopy, 66(Suppl.1) (Suppl.1), 993 - 993, 日本語Walled-off necrosisに対するEUS-guided drainage後のstep-up治療法別の成績 WONDERFUL study group
- BACKGROUND: Focal parenchymal atrophy and main pancreatic duct (MPD) dilatation have been identified as early signs of pancreatic ductal adenocarcinoma. However, limited evidence exists regarding their temporal progression due to previous study limitations with restricted case numbers. OBJECTIVE: To ascertain a more precise frequency assessment of suspicious pancreatic ductal adenocarcinoma findings as well as delineate the temporal progression of them. METHODS: A multicenter retrospective study was conducted on patients diagnosed with pancreatic ductal adenocarcinoma between 2015 and 2021. We included patients who had undergone at least one computed tomography (CT) scan ≥6 months before diagnosing pancreatic ductal adenocarcinoma. The temporal progression of suspicious pancreatic ductal adenocarcinoma findings on CT was investigated. RESULTS: Out of 1832 patients diagnosed with pancreatic ductal adenocarcinoma, 320 had a previous CT before their diagnosis. Suspicious pancreatic ductal adenocarcinoma findings were detected in 153 cases (47.8%), with focal parenchymal atrophy (26.6%) being the most common followed by MPD dilatation (11.3%). Focal parenchymal atrophy was the earliest detectable sign among all suspicious findings and became visible on average 2.7 years before diagnosis, and the next most common, MPD dilatation, 1.1 years before diagnosis. Other findings, such as retention cysts, were less frequent and appeared around 1 year before diagnosis. Focal parenchymal atrophy followed by MPD dilatation was observed in 10 patients but not in reverse order. Focal parenchymal atrophy was more frequently detected in the pancreatic body/tail. No significant relationship was found between the pathological pancreatic ductal adenocarcinoma differentiation or tumor stage and the time course of the CT findings. All cases of focal parenchymal atrophy progressed just prior to diagnosis, and the atrophic area was occupied by tumor at diagnosis. Main pancreatic duct dilatation continued to progress until diagnosis. CONCLUSION: This large-scale study revealed that the temporal progression of focal parenchymal atrophy is the earliest detectable sign indicating pancreatic ductal adenocarcinoma. These results provide crucial insights for early pancreatic ductal adenocarcinoma detection.2024年03月, United European gastroenterology journal, 英語, 国際誌研究論文（学術雑誌）
- (一財)日本消化器病学会, 2024年03月, 日本消化器病学会雑誌, 121(臨増総会) (臨増総会), A81 - A81, 日本語
- (一財)日本消化器病学会, 2024年03月, 日本消化器病学会雑誌, 121(臨増総会) (臨増総会), A187 - A187, 日本語
- (一財)日本消化器病学会, 2024年03月, 日本消化器病学会雑誌, 121(臨増総会) (臨増総会), A431 - A431, 日本語
- BACKGROUND: The impact of extended steroid administration on patients with autoimmune pancreatitis after a 3-year maintenance period remains poorly understood. This study analyzed the advantage and disadvantage of continuing steroid therapy beyond 3 years. METHODS: In this retrospective multicenter study across 17 institutions, patients who successfully completed 3 years of maintenance therapy without experiencing relapse were categorized into two groups: the maintenance therapy discontinuation group, who discontinued steroid therapy after the initial 3-year period, and maintenance therapy continuation group, who continued steroid therapy beyond 3 years. The cumulative relapse rate after 3 years of maintenance therapy was the primary outcome. Relapse predictors were compared using the Gray test for cumulative relapse incidence by specific factor. RESULTS: Of 211 patients, 105 experienced no relapse during the 3-year maintenance therapy and were divided into two groups: 69 in the maintenance therapy discontinuation group and 36 in the maintenance therapy continuation group. The relapse rate was lower in the maintenance therapy continuation group than in the maintenance therapy discontinuation group (P = 0.035). Predictors of relapse after 3 years included cessation of maintenance therapy (hazard ratio [HR] = 3.76; 95 % confidence interval [CI] = 1.07-13.3, P = 0.040) and renal involvement (HR = 2.88; 95 % CI = 1.04-7.99, P = 0.042). The maintenance therapy continuation group showed a significantly higher prevalence of macrovascular complications, compared with the maintenance therapy discontinuation group (P = 0.005). CONCLUSIONS: Cessation of steroid maintenance therapy and renal involvement were predictors of relapse after 3 years of maintenance therapy. However, the long-term use of steroids may increase the risk of macrovascular complications.2024年01月, Pancreatology : official journal of the International Association of Pancreatology (IAP) ... [et al.], 英語, 国際誌研究論文（学術雑誌）
- BACKGROUND: Recent evidence suggests that the presence of microbiome within human pancreatic ductal adenocarcinoma (PDAC) tissue potentially influences cancer progression and prognosis. However, the significance of tumor-resident microbiome remains unclear. We aimed to elucidate the impact of intratumoral bacteria on the pathophysiology and prognosis of human PDAC. METHODS: The presence of intratumoral bacteria was assessed in 162 surgically resected PDACs using quantitative polymerase chain reaction (qPCR) and in situ hybridization (ISH) targeting 16S rRNA. The intratumoral microbiome was explored by 16S metagenome sequencing using DNA extracted from formalin-fixed paraffin-embedded tissues. The profile of intratumoral bacteria was compared with clinical information, pathological findings including tumor-infiltrating T cells, tumor-associated macrophage, fibrosis, and alterations in four main driver genes (KRAS, TP53, CDKN2A/p16, SMAD4) in tumor genomes. RESULTS: The presence of intratumoral bacteria was confirmed in 52 tumors (32%) using both qPCR and ISH. The 16S metagenome sequencing revealed characteristic bacterial profiles within these tumors, including phyla such as Proteobacteria and Firmicutes. Comparison of bacterial profiles between cases with good and poor prognosis revealed a significant positive correlation between a shorter survival time and the presence of anaerobic bacteria such as Bacteroides, Lactobacillus, and Peptoniphilus. The abundance of these bacteria was correlated with a decrease in the number of tumor-infiltrating T cells positive for CD4, CD8, and CD45RO. CONCLUSIONS: Intratumoral infection of anaerobic bacteria such as Bacteroides, Lactobacillus, and Peptoniphilus is correlated with the suppressed anti-PDAC immunity and poor prognosis.2024年01月, Journal of gastroenterology, 英語, 国内誌研究論文（学術雑誌）
- 日本消化器病学会-近畿支部, 2024年01月, 日本消化器病学会近畿支部例会プログラム・抄録集, 120回, 70 - 70, 日本語
- 2024年01月, Journal of medical ultrasonics (2001), 51(1) (1), 143 - 144, 英語, 国内誌研究論文（学術雑誌）
- 日本消化器内視鏡学会-近畿支部, 2023年11月, 日本消化器内視鏡学会近畿支部例会プログラム・抄録集, 111回, 109 - 109, 日本語経口胆道鏡が有用であった胆嚢管癌の一例
- OBJECTIVES: Aging is associated with a high prevalence of pancreatic cysts and intraductal papillary mucinous neoplasms (IPMNs). Metabolic syndrome (MS) may increase the risk of neoplasms, including those that develop in the pancreas. However, the influence of factors associated with MS on the development of IPMN remains unclear. METHODS: A total of 9363 patients who underwent abdominal ultrasound examinations between April 2012 and May 2013 were included in this study. Multivariate logistic regression analysis was performed to identify factors associated with the presence of IPMN by age. RESULTS: Pancreatic cysts were detected in 198 of 9363 patients, of whom 129 were found to have IPMNs. The presence of IPMN significantly correlated with age (10-year increments; odds ratio, 2.73; 95% CI, 2.28-3.29; P < 0.001). High body mass index, history of smoking, hyperlipidemia, hypertension, and MS were associated with a higher prevalence of IPMN with advancing age. In multivariate analysis, the presence of IPMN was more frequent in elderly patients with MS (odds ratio, 3.14; 95% CI, 3.14-6.72; P = 0.003). CONCLUSIONS: The present study suggests that the incidence of IPMN increases with age and is accelerated in the presence of MS.2023年10月, Pancreas, 英語, 国際誌研究論文（学術雑誌）
- Intraductal papillary mucinous neoplasm (IPMN) is a premalignant lesion of the pancreas that can occasionally manifest as recurrent acute pancreatitis. In this report, we discuss a unique case of a 49-year-old woman who presented with recurrent acute pancreatitis of an unknown cause for several years. Workup using peroral pancreatoscopy eventually showed main-duct IPMN with high-grade dysplasia as the obscure cause of recurrent acute pancreatitis. This case report highlights the clinical course of main-duct IPMN and the evolving role of peroral pancreatoscopy in patients with recurrent acute pancreatitis.2023年10月, ACG case reports journal, 10(10) (10), e01165, 英語, 国際誌
- (一社)日本癌学会, 2023年09月, 日本癌学会総会記事, 82回, 1929 - 1929, 英語膵癌の腫瘍間質膠原線維量と分子病理学的特徴、腫瘍免疫、予後との関連性(Association of Tumor-Stromal Collagen Quantity in PDAC with Molecular Pathology, Tumor Immunity, and Prognosis)
- Pancreatic cancer primarily arises from microscopic precancerous lesions, such as pancreatic intraepithelial neoplasia (PanIN) and acinar-to-ductal metaplasia (ADM). However, no established method exists for predicting pancreatic precancerous conditions. Endoscopic ultrasonography (EUS) can detect changes in pancreatic parenchymal histology, including fibrosis. This study aimed to elucidate the relationship between pancreatic parenchymal EUS findings and microscopic precancerous lesions. We retrospectively analyzed 114 patients with pancreatobiliary tumors resected between 2010 and 2020 and evaluated the association between pancreatic parenchymal EUS findings and the number of PanIN, ADM, and pancreatic duct gland (PDG). Of the 114 patients, 33 (29.0%), 55 (48.2%), and 26 (22.8%) had normal EUS findings, hyperechoic foci/stranding without lobularity, and hyperechoic foci/stranding with lobularity, respectively. Multivariate analyses revealed that abnormal EUS findings were significantly associated with the frequency of PanIN (hyperechoic foci/stranding without lobularity: OR [95% CI] = 2.7 [1.0-7.3], with lobularity: 6.5 [1.9-22.5], Ptrend = 0.01) and ADM (hyperechoic foci/stranding without lobularity: 3.1 [1.1-8.2], with lobularity: 9.7 [2.6-36.3], Ptrend = 0.003) but not with PDG (hyperechoic foci/stranding without lobularity: 2.2 [0.8-5.8], with lobularity: 3.2 [1.0-10.2], Ptrend = 0.12). We observed a trend toward a significantly higher number of precancerous lesions in the following order: normal findings, hyperechoic foci/stranding without lobularity, and hyperechoic foci/stranding with lobularity. Pancreatic parenchymal EUS findings were associated with the increased frequency of PanIN and ADM. Lobularity may help predict the increased number of precancerous lesions.2023年07月, Scientific reports, 13(1) (1), 12052 - 12052, 英語, 国際誌研究論文（学術雑誌）
- BACKGROUND: Abundant collagen deposition is a hallmark of pancreatic ductal adenocarcinomas (PDACs). This study clarified the interactive relationship between tumor-stromal collagen, molecular and immune characteristics, and tumor pr ogression in human PDAC. METHODS: We performed a comprehensive examination using an integrative molecular pathological epidemiology database on 169 cases with resected PDAC . The amount of tumor-stromal collagen was quantified through digital imaging analysis for Elastica van Gieson-stained whole-section tumor slides. We analyzed the association of tumor-stromal collagen with gene alterations (KRAS, TP53, CDKN2A/p16, and SMAD4), immune parameters (CD4+ tumor-infiltrating lymphocytes [TILs], CD8+ TILs, FOXP3+ TILs, and tertiary lymphoid structures), and patient prognosis. RESULTS: Low amounts of tumor-stromal collagen were associated with poor differentiation (multivariable OR = 3.82, 95%CI = 1.41-12.2, P = 0.008) and CDKN2A/p16 alteration (OR [95%CI] = 2.06 [1.08-4.02], P = 0.03). Tumors with low collagen levels had shorter overall survival (HR [95%CI] = 2.38 [1.59-3.56], P < 0.0001). In the S-1 and gemcitabine (GEM) treatment groups, low tumor-stromal collagen was linked to poor prognosis of patients with PDAC (S-1 group: multivariable HR [95%CI] = 2.76 [1.36-5.79], P = 0.005; GEM group: multivariate HR [95%CI] = 2.91 [1.34-6.71], P = 0.007). Additionally, low amounts of tumor-stromal collagen were also linked to low levels of CD4+ TILs (P = 0.046), CD8+ TILs (P = 0.09), and tertiary lymphoid structures (P = 0.001). CONCLUSIONS: Tumor-stromal collagen deposition may play a crucial role in modulating tumor-immune microenvironment and determining response to adjuvant chemotherapy and patient survival outcomes.2023年07月, Journal of gastroenterology, 58(10) (10), 1055 - 1067, 英語, 国内誌研究論文（学術雑誌）
- (一社)日本膵臓学会, 2023年07月, 膵臓, 38(3) (3), A369 - A369, 日本語
- 2023年06月, Annals of surgical oncology, 30(9) (9), 5790 - 5791, 英語, 国際誌研究論文（学術雑誌）
- A 75-year-old Japanese woman visited a hospital with a stomachache. The patient was diagnosed with localized mild acute pancreatitis. Blood tests revealed elevated serum IgG4 levels. Contrast-enhanced computed tomography showed a hypovascular mass, 3 cm in size, in the pancreatic body with dilation of the upstream duct. Additionally, it showed another tumorous lesion of 10 mm in size in the anterior wall of the stomach, and endoscopic examination confirmed a submucosal tumor (SMT) sized 10 mm in the anterior wall of the stomach. Endoscopic ultrasound-guided fine needle aspiration biopsy (EUS-FNAB) of the pancreas revealed an adenocarcinoma concomitant with marked IgG4-positive cell infiltration. Hence, distal pancreatectomy with local gastrectomy was performed, and the final diagnosis was concluded as pancreatic ductal adenocarcinoma (PDAC) complicated by IgG4-related diseases (IgG4-RD) in the pancreas and stomach. IgG4-RD of the digestive tract is exceedingly rare. The correlation between PDAC and autoimmune pancreatitis or malignancy and IgG4-RD is controversial. However, the clinical course and histopathological examination, in this case, provide valuable suggestive findings for further discussion.2023年05月, Clinical journal of gastroenterology, 16(5) (5), 785 - 790, 英語, 国内誌研究論文（学術雑誌）
- BACKGROUND: Sarcopenia, defined as a loss of skeletal muscle mass and quality, is found in 30-65% of patients with pancreatic ductal adenocarcinoma (PDAC) at diagnosis, and is a poor prognostic factor. However, it is yet to be evaluated why sarcopenia is associated with poor prognosis. Therefore, this study elucidated the tumor characteristics of PDAC with sarcopenia, including driver gene alterations and tumor microenvironment. PATIENTS AND METHODS: We retrospectively analyzed 162 patients with PDAC who underwent pancreatic surgery between 2008 and 2017. We defined sarcopenia by measuring the skeletal muscle mass at the L3 level using preoperative computed tomography images and evaluated driver gene alteration (KRAS, TP53, CDKN2A/p16, and SMAD4) and tumor immune (CD4+, CD8+, and FOXP3+) and fibrosis status (stromal collagen). RESULTS: In localized-stage PDAC (stage ≤ IIa), overall survival (OS) and recurrence-free survival were significantly shorter in the sarcopenia group than in the non-sarcopenia group (2-year OS 89.7% versus 59.1%, P = 0.03; 2-year RFS 74.9% versus 50.0%, P = 0.02). Multivariate analysis revealed that sarcopenia was an independent poor prognostic factor in localized-stage PDAC. Additionally, tumor-infiltrating CD8+ T cells in the sarcopenia group were significantly less than in the non-sarcopenia group (P = 0.02). However, no difference was observed in driver gene alteration and fib.rotic status. These findings were not observed in advanced-stage PDAC (stage ≥ IIb). CONCLUSIONS: Sarcopenia was associated with a worse prognosis and decreased tumor-infiltrating CD8+ T cells in localized-stage PDAC. Sarcopenia may worsen a patient's prognosis by suppressing local tumor immunity.2023年05月, Annals of surgical oncology, 30(9) (9), 5776 - 5787, 英語, 国際誌研究論文（学術雑誌）
- BACKGROUND: Tertiary lymphoid structure (TLS) reflects an intense immune response against cancer, which correlates with favorable patient survival. However, the association of TLS with tumor-infiltrating lymphocytes (TILs) and clinical outcomes has not been investigated comprehensively in pancreatic ductal adenocarcinoma (PDAC). METHODS: We utilized an integrative molecular pathological epidemiology database on 162 cases with resected PDAC, and examined TLS in relation to levels of TILs, patient survival, and treatment response. In whole-section slides, we assessed the formation of TLS and conducted immunohistochemistry for tumor-infiltrating T cells (CD4, CD8, CD45RO, and FOXP3). As confounding factors, we assessed alterations of four main driver genes (KRAS, TP53, CDKN2A [p16], and SMAD4) using next-generation sequencing and immunohistochemistry, and tumor CD274 (PD-L1) expression assessed by immunohistochemistry. RESULTS: TLSs were found in 112 patients with PDAC (69.1%). TLS was associated with high levels of CD4+ TILs (multivariable odds ratio [OR], 3.50; 95% confidence interval [CI] 1.65-7.80; P = 0.0002), CD8+ TILs (multivariable OR, 11.0; 95% CI 4.57-29.7, P < 0.0001) and CD45RO+ TILs (multivariable OR, 2.65; 95% CI 1.25-5.80, P = 0.01), but not with levels of FOXP3+ TILs. TLS was associated with longer pancreatic cancer-specific survival (multivariable hazard ratio, 0.37; 95% CI 0.25-0.56, P < 0.0001) and favorable outcomes of adjuvant S-1-treatment. TLS was not associated with driver gene alterations but tumor CD274 negative expression. CONCLUSIONS: Our comprehensive data supports the surrogacy of TLS for vigorous anti-tumor immune response characterized by high levels of helper and cytotoxic T cells and their prognostic role.2023年01月, Journal of gastroenterology, 58(3) (3), 277 - 291, 英語, 国内誌研究論文（学術雑誌）
- When the etiology of pancreatitis cannot be determined despite sufficient investigation, recurrence and progression to chronic pancreatitis often involve genetic mutations. Herein, we describe a case of recurrent pancreatitis with the IVS3+2T>C mutation in the serine protease inhibitor Kazal type 1 (SPINK1) gene that progressed to chronic pancreatitis in only 3 years. A 35-year-old man was referred to our hospital, where he was diagnosed with mild pancreatitis and was treated conservatively. However, the patient experienced recurrent episodes of pancreatitis, which progressed to become chronic pancreatitis with a pancreatic calcification 1 year later. After 3 years, the patient developed pancreatic duct stenosis and required a pancreatic duct stent placement. Regarding the cause of chronic pancreatitis, alcohol abuse was ruled out based on history taking. Considering the course of treatment, autoimmune pancreatitis and obstructive pancreatitis, such as pancreatic divisum, were also ruled out. Finally, a germline genetic test was performed to determine the etiology of pancreatitis, which revealed the IVS3+2T>C mutation in SPINK1. This case shows the importance of genetic testing in patients with idiopathic pancreatitis to determine their etiology and is a rare incident that can report the progression of the disease from acute to chronic pancreatitis.2023年, Case reports in gastroenterology, 17(1) (1), 49 - 55, 英語, 国際誌
- BACKGROUND AND AIM: Endoscopic ultrasonography (EUS) findings of the pancreatic parenchyma, such as hyperechoic foci/stranding and lobularity, may be associated with the severity of chronic pancreatitis (CP). However, the correlation between parenchymal EUS findings and histology remains unclear. We designed a large-scale retrospective study analyzing over 200 surgical specimens to elucidate the association between parenchymal EUS findings and histological features. METHODS: Clinical data of 221 patients with pancreatobiliary tumors who underwent preoperative EUS and pancreatic surgery between January 2010 and November 2020 were reviewed to investigate the association between parenchymal EUS findings and histological features at the pancreatic body. None of these patients met the definition of CP. RESULTS: Of the 221 patients, 87 (39.4%), 89 (40.2%), and 45 (20.4%) had normal EUS findings, hyperechoic foci/stranding without lobularity, and hyperechoic foci/stranding with lobularity, respectively. In the multivariate analyses, parenchymal EUS findings significantly correlated with histological CP findings of fibrosis, inflammation, and atrophy (hyperechoic foci/stranding without lobularity vs hyperechoic foci/stranding with lobularity, odds ratio [95% confidence interval]: 4.1 [2.2-7.9] vs 31.3 [9.3-105.6], Ptrend < 0.001; 3.9 [1.9-8.2] vs 21.8 [8.0-59.4], Ptrend < 0.001; and 4.0 [2.0-7.8] vs 22.9 [7.0-74.5], Ptrend < 0.001, respectively). Further, a trend toward higher histological grade was observed in the following order: normal findings, hyperechoic foci/stranding without lobularity, and hyperechoic foci/stranding with lobularity. CONCLUSIONS: Endoscopic ultrasonography findings of the pancreatic parenchyma may be associated with the histological conditions in CP, such as pancreatic fibrosis, inflammation, and atrophy. Lobularity reflects more severe histological conditions than does hyperechoic foci/stranding.2022年10月, Journal of gastroenterology and hepatology, 38(1) (1), 103 - 111, 英語, 国際誌研究論文（学術雑誌）
- BACKGROUND: A step-up approach is recommended as a new treatment algorithm for pancreatic fluid collections (PFCs). However, determining which patients with PFCs require a step-up approach after endoscopic ultrasound-guided transmural drainage (EUS-TD) is unclear. If the need for a step-up approach could be predicted, it could be performed early for relevant patients. We aimed to identify PFC-related predictive factors for a step-up approach after EUS-TD. METHODS: This retrospective cohort study included consecutive patients who had undergone EUS-TD for PFCs from January 2008 to May 2020. Multivariable logistic regression analyses were performed to investigate PFC factors related to requiring a step-up approach. A step-up approach was performed for patients who did not respond clinically to EUS-TD. RESULTS: We enrolled 81 patients, of whom 25 (30.9%) required a step-up approach. In multivariate logistic regression analysis, the pre-EUS-TD number of PFC-occupied regions ≥ 3 (multivariate odds ratio [OR] 16.2, 95% confidence interval [CI] 2.68-97.6, P = 0.002), the post-EUS-TD PFC-remaining percentage ≥ 35% (multivariate OR 19.9, 95% CI 2.91-136.1, P = 0.002), and a positive sponge sign, which is a distinctive computed tomography finding in the early stage after EUS-TD (multivariate OR 6.26, 95% CI 1.33-29.3, P = 0.020), were independent predictive factors associated with requiring a step-up approach for PFCs. CONCLUSION: Pre-EUS-TD PFC-occupied regions, post-EUS-TD PFC-remaining percentage, and a positive sponge sign were predictors of the need for a step-up approach. Patients with PFC with these findings should be offered a step-up approach whereas conservative treatment is recommended for patients without these findings. CLINICAL REGISTRATION NUMBER: UMIN 000030898.2022年09月, Surgical endoscopy, 37(2) (2), 1096 - 1106, 英語, 国際誌研究論文（学術雑誌）
- Endoscopic papillectomy for early ampullary tumors is considered a minimally invasive and useful alternative to pancreatoduodenectomy; however, its indications remain unclear. This study aimed to clarify the advantages of endoscopic papillectomy by investigating the clinical outcomes of patients who underwent endoscopic papillectomy or pancreatoduodenectomy for early ampullary tumors. Patients diagnosed with early ampullary tumors (adenoma, Tis, T1a) who underwent endoscopic papillectomy or pancreatoduodenectomy between June 2008 and October 2019 were included, and their clinical outcomes were analyzed. Seventy-four patients (34 patients with adenomas and 40 patients with adenocarcinomas) were divided into two groups, namely endoscopic papillectomy (n = 43) and pancreatoduodenectomy (n = 31). The estimated 5-year overall survival rate of all early ampullary tumors was 92%. Complete resection rate was significantly lower for endoscopic papillectomy patients versus pancreatoduodenectomy patients (48.8% vs. 100%; p < 0.001). Recurrence was more common in the endoscopic papillectomy group compared to the pancreatoduodenectomy group (16.3% vs. 3.2%; p = 0.128), but all recurrences were controllable by endoscopic treatment. The median length of hospital stay for the endoscopic papillectomy group was significantly shorter compared to the endoscopic papillectomy group (11 days vs. 42 days; p < 0.001). The Comprehensive Complication Index was significantly lower in the endoscopic papillectomy group compared to the pancreatoduodenectomy group (14.8 vs 22.6%; p = 0.002). Endoscopic papillectomy for early ampullary tumors is useful and may be an alternative treatment for pancreatoduodenectomy in selected cases.NATURE PORTFOLIO, 2022年09月, SCIENTIFIC REPORTS, 12(1) (1), 英語研究論文（学術雑誌）
- Background A step-up approach is recommended as a new treatment algorithm for pancreatic fluid collections (PFCs). However, determining which patients with PFCs require a step-up approach after endoscopic ultrasound-guided transmural drainage (EUS-TD) is unclear. If the need for a step-up approach could be predicted, it could be performed early for relevant patients. We aimed to identify PFC-related predictive factors for a step-up approach after EUS-TD. Methods This retrospective cohort study included consecutive patients who had undergone EUS-TD for PFCs from January 2008 to May 2020. Multivariable logistic regression analyses were performed to investigate PFC factors related to requiring a step-up approach. A step-up approach was performed for patients who did not respond clinically to EUS-TD. Results We enrolled 81 patients, of whom 25 (30.9%) required a step-up approach. In multivariate logistic regression analysis, the pre-EUS-TD number of PFC-occupied regions >= 3 (multivariate odds ratio [OR] 16.2, 95% confidence interval [CI] 2.68-97.6, P = 0.002), the post-EUS-TD PFC-remaining percentage >= 35% (multivariate OR 19.9, 95% CI 2.91-136.1, P = 0.002), and a positive sponge sign, which is a distinctive computed tomography finding in the early stage after EUS-TD (multivariate OR 6.26, 95% CI 1.33-29.3, P = 0.020), were independent predictive factors associated with requiring a step-up approach for PFCs. Conclusion Pre-EUS-TD PFC-occupied regions, post-EUS-TD PFC-remaining percentage, and a positive sponge sign were predictors of the need for a step-up approach. Patients with PFC with these findings should be offered a step-up approach whereas conservative treatment is recommended for patients without these findings. Clinical registration number UMIN 000030898.SPRINGER, 2022年09月, SURGICAL ENDOSCOPY AND OTHER INTERVENTIONAL TECHNIQUES, 英語研究論文（学術雑誌）
- 膵外分泌はコレシストキニン(CCK)などの消化管ホルモンが腺房細胞に存在する受容体に結合することによって起こる。膵外分泌は細胞内Ca2+濃度によって厳格に制御されているが、過剰なCCK刺激が腺房細胞に加わると細胞内Ca2+濃度の恒常性が破綻して膵外分泌不全に陥る。このとき、腺房細胞内ではCCKが受容体に結合することにより、ホスホリパーゼC(PLC)を介して、イノシトール三リン酸(IP3)とジアシルグリセロール(DAG)が産生される。IP3は小胞体からの細胞内Ca2+放出を促し、細胞内Ca2+濃度が持続的な異常高値状態になる。引き続き、膵外分泌不全やNF-κB経路の活性化といった複合的な異常が並行して進行し膵炎に至る。CCK受容体への刺激を細胞内に伝えるPLC epsilon(PLCε)は他臓器において炎症とのかかわりが示唆されているPLCのサブタイプの一つである。われわれはPLCεの膵炎時の機能解析を通じて、膵炎時の腺房細胞における炎症制御機構を検討しており、本稿ではその一端を紹介する。今後も、膵炎の新規治療ターゲットを見出すために膵炎時の腺房細胞内シグナル伝達経路の詳細な解明が期待される。(著者抄録)医学図書出版(株), 2022年08月, 胆と膵, 43(8) (8), 751 - 757, 日本語
- BACKGROUND: Secondary sclerosing cholangitis, characterized by biliary obstruction, can be caused by drugs such as immune checkpoint inhibitors (ICIs). While there a few reports of sclerosing cholangitis after immune checkpoint inhibitor administration, no case has been reported after discontinuation of such drugs. CASE SUMMARY: A 68-year-old man who underwent chemotherapy for lung adenocarcinoma with bone metastasis presented with abdominal pain and fever 4 mo after the final administration of pembrolizumab. Computed tomography revealed thickening of the gallbladder wall and dilatation of the common bile duct. Endoscopic retro-grade cholangiopancreatography revealed an irregularly narrowed intrahepatic bile duct. Biopsy of the bile duct demonstrated that CD8+ T cells were predominant over CD4+ T cells. Liver biopsy showed dominant infiltration of CD8+ T in the portal tract, but onion-skin lesions were not observed. The patient was diagnosed with immune-related sclerosing cholangitis induced by pembrolizumab. Administration of methylprednisolone and endoscopic nasobiliary drainage were performed, but the cholangiography and laboratory test findings did not improve. No further treatment was administered due to disease progression, and the patient was referred for palliative care. CONCLUSION: Immune-related sclerosing cholangitis may have a late onset, and such cases occurring after discontinuation of ICIs should be carefully managed.2022年07月, World journal of gastroenterology, 28(28) (28), 3732 - 3738, 英語, 国際誌
- 日本消化器内視鏡学会-近畿支部, 2022年06月, 日本消化器内視鏡学会近畿支部例会プログラム・抄録集, 108回, 50 - 50, 日本語胆膵内視鏡治療の工夫とリスクマネージメント 急性膵炎局所合併症における治療困難例の特徴と早期インターベンションの可能性
- 日本消化器内視鏡学会-近畿支部, 2022年06月, 日本消化器内視鏡学会近畿支部例会プログラム・抄録集, 108回, 85 - 85, 日本語胆管空腸吻合部狭窄に対して直視型EUSを用いて再建腸管からの胆管空腸瘻孔形成術に成功した1例
- 日本消化器内視鏡学会-近畿支部, 2022年06月, 日本消化器内視鏡学会近畿支部例会プログラム・抄録集, 108回, 85 - 85, 日本語胆管空腸吻合部狭窄に対して直視型EUSを用いて再建腸管からの胆管空腸瘻孔形成術に成功した1例
- BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) concomitant with intraductal papillary mucinous neoplasm (IPMN) is defined as PDAC occurring apart from IPMN. This study comprehensively investigated the molecular biologic characteristics of PDAC concomitant with IPMN in major genetic alterations, tumor microenvironment, and prognosis by contrast with those of conventional PDAC. METHODS: The study retrospectively reviewed the data of 158 surgically resected PDAC patients. The driver gene alteration status (KRAS, TP53, CDKN2A, SMAD4, and GNAS) together with the immune and fibrotic status in tumor was evaluated. The prognosis of PDAC concomitant with IPMN and that of conventional PDAC also were compared. RESULTS: No statistically significant difference was found between PDAC concomitant with IPMN and conventional PDAC in the alteration frequency analysis of the major driver genes and the immune and fibrotic status in the tumor microenvironment. Overall survival and disease-free survival between patients who had PDAC concomitant with IPMN and those who had conventional PDAC did not show statistically significant differences in propensity-matched subjects. Furthermore, the co-existence of IPMN was not a poor prognostic factor in the multivariable-adjusted Cox proportional hazards model (hazard ratio, 0.95; 95 % confidence interval, 0.51-1.78). CONCLUSIONS: In this study, PDAC concomitant with IPMN had tumor characteristics similar to those of conventional PDAC in terms of the major driver gene alterations, tumor microenvironment, and prognosis.2022年05月, Annals of surgical oncology, 29(8) (8), 4924 - 4934, 英語, 国際誌研究論文（学術雑誌）
- 2022年05月, Annals of surgical oncology, 英語, 国際誌研究論文（学術雑誌）
- (一社)日本消化器内視鏡学会, 2022年04月, Gastroenterological Endoscopy, 64(Suppl.1) (Suppl.1), 810 - 810, 日本語悪性輸入脚狭窄に対する内視鏡的ステント留置術の検討
- (一社)日本消化器内視鏡学会, 2022年04月, Gastroenterological Endoscopy, 64(Suppl.1) (Suppl.1), 766 - 766, 日本語Pancreatic fluid collectionに対する早期インターベンションの可能性
- (一社)日本消化器内視鏡学会, 2022年04月, Gastroenterological Endoscopy, 64(Suppl.1) (Suppl.1), 810 - 810, 日本語悪性輸入脚狭窄に対する内視鏡的ステント留置術の検討
- (一財)日本消化器病学会, 2022年03月, 日本消化器病学会雑誌, 119(臨増総会) (臨増総会), A88 - A88, 日本語
- 日本消化器内視鏡学会-近畿支部, 2021年12月, 日本消化器内視鏡学会近畿支部例会プログラム・抄録集, 107回, 89 - 89, 日本語合流部結石による胆嚢結腸瘻の一例
- 日本消化器内視鏡学会-近畿支部, 2021年12月, 日本消化器内視鏡学会近畿支部例会プログラム・抄録集, 107回, 93 - 93, 日本語膵臓に多発結節を認めEUS-FNAで診断し得たAIDS関連バーキットリンパ腫の一例
- 2021年11月, Digestive and liver disease : official journal of the Italian Society of Gastroenterology and the Italian Association for the Study of the Liver, 53(11) (11), 1511 - 1512, 英語, 国際誌研究論文（学術雑誌）
- BACKGROUND AND AIMS: Consensus regarding an optimal algorithm for endoscopic treatment of papillary adenomas has not been established. We aimed to assess the existing degree of consensus among international experts and develop further concordance by means of a Delphi process. METHODS: Fifty-two international experts in the field of endoscopic papillectomy were invited to participate. Data were collected between August and December 2019 using an online survey platform. Three rounds were conducted. Consensus was defined as ≥70% agreement. RESULTS: Sixteen experts (31%) completed the full process, and consensus was achieved on 47 of the final 79 statements (59%). Diagnostic workup should include at least an upper endoscopy using a duodenoscope (100%) and biopsy sampling (94%). There should be selected use of additional abdominal imaging (75%-81%). Patients with (suspected) papillary malignancy or over 1 cm intraductal extension should be referred for surgical resection (76%). To prevent pancreatitis, rectal nonsteroidal anti-inflammatory drugs should be administered before resection (82%) and a pancreatic stent should be placed (100%). A biliary stent is indicated in case of ongoing bleeding from the papillary region (76%) or concerns for a (micro)perforation after resection (88%). Follow-up should be started 3 to 6 months after initial papillectomy and repeated every 6 to 12 months for at least 5 years (75%). CONCLUSIONS: This is the first step in developing an international consensus-based algorithm for endoscopic management of papillary adenomas. Surprisingly, in many areas consensus could not be achieved. These aspects should be the focus of future studies.2021年10月, Gastrointestinal endoscopy, 94(4) (4), 760 - 773, 英語, 国際誌研究論文（学術雑誌）
- 急性膵炎後の局所合併症である膵仮性嚢胞(PPC)や被包化膵壊死(WON)に対する治療法として、EUS下経消化管的ドレナージから内視鏡的ネクロセクトミーへと治療効果に応じて侵襲度を上げていく内視鏡的step-up approachが普及しつつある。さらにLAMSの登場によって、従来のプラスチックステントよりも効率的なドレナージが可能となった。しかし最近のランダム化比較試験において、LAMSを長期間留置することによりステント関連の偶発症発生率が高くなることが示されたため、画像による定期的なフォローやWONが改善した場合は留置後3週間以内の抜去が提案されている。今後はさらなる治療成績の向上と、偶発症の低減を目指したストラテジーの立案が期待される。(著者抄録)(株)東京医学社, 2021年09月, 消化器内視鏡, 33(9) (9), 1467 - 1475, 日本語
- 日本消化器病学会-近畿支部, 2021年09月, 日本消化器病学会近畿支部例会プログラム・抄録集, 115回, 91 - 91, 日本語自己免疫性膵炎を背景とした膵頭部に肺癌転移を来した一例
- BACKGROUND/PURPOSE: The purpose of the present study was to investigate the possibility of reducing clinical impacts of acute necrotic collection (ANC) on patients with acute pancreatitis (AP) using recombinant human soluble thrombomodulin (rTM). METHODS: In this retrospective multicenter study, 233 consecutive AP patients with ANC and acute peripancreatic fluid collection (APFC) from 2012 to 2016 were enrolled. To assess clinical impacts of ANC, severity on admission (JPN score, JPN CT grade, and Modified CT severity index), development of walled-off necrosis (WON), imaging costs for follow-up, and mortality were recorded. Finally, we investigated whether rTM could reduce the clinical impacts, adjusting the severity using propensity analysis with Inverse probability of treatment weighting. RESULTS: Patients with ANC developed WON with higher ratio than APFC (58/98 [59.2%] vs 20/135 [14.8%], OR = 8.3, P < .01]. Severity on admission and imaging costs for follow-up in ANC patients were significantly higher than those in APFC (P < .01). However, regarding mortality, there was no significant difference between patients with ANC and APFC (P = .41). Adjusting severity, it was revealed that rTM administration significantly reduced the risk of ANC developed WON (OR = 0.23, P = .01). CONCLUSIONS: While ANC had a higher clinical impact than that of APFC, we found that early administration of rTM may reduce the impact.2021年09月, Journal of hepato-biliary-pancreatic sciences, 28(9) (9), 788 - 797, 英語, 国内誌研究論文（学術雑誌）
- Purpose 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.2021年08月, Internal medicine (Tokyo, Japan), 英語, 国内誌研究論文（学術雑誌）
- (一社)日本胆道学会, 2021年08月, 胆道, 35(3) (3), 505 - 505, 日本語
- (一社)日本膵臓学会, 2021年08月, 膵臓, 36(3) (3), A236 - A236, 日本語膵炎・膵癌のbench to bed:病態解明から新規治療法開発に向けて 急性膵炎におけるPLCεを介した炎症制御機構の解明
- (一社)日本膵臓学会, 2021年08月, 膵臓, 36(3) (3), A142 - A142, 日本語急性膵炎診療をめぐる諸問題 Walled-off necrosisに対する内視鏡的治療戦略
- (一社)日本膵臓学会, 2021年08月, 膵臓, 36(3) (3), A209 - A209, 日本語IgG4関連疾患up-to-date:病態、診断、治療の最新知見 当院における自己免疫性膵炎の長期予後と悪性腫瘍の発症および再燃リスク因子の検討
- Afferent loop obstruction (ALO) is defined as duodenal or jejunal mechanical obstruction at the proximal anastomosis site of a gastrojejunostomy. With advances in chemotherapy, the incidence of malignant ALO is increasing. Malignant ALO can be complicated by ischemia, gangrenous bowel, pancreatitis, and ascending cholangitis. Moreover, the general condition of patients with recurrent cancer is often poor. Therefore, accurate and rapid diagnosis and minimally invasive treatments are required. However, no review articles on the diagnosis and treatment of malignant ALO have been published. Through literature searching, we reviewed related articles published between 1959 and 2020 in the PubMed database. Herein, we present recent advances in the diagnosis and treatment of malignant ALO and describe future perspectives. Endoscopic transluminal self-expandable metal stent (SEMS) placement is considered the standard treatment for malignant ALO, as this procedure is well established and less invasive. However, with the development of interventional endoscopic ultrasound (EUS) in recent years, the usefulness of EUS-guided gastrojejunostomy has been reported. Moreover, through indirect comparison, this approach has been reported to be superior to transluminal SEMS placement. It is expected that a safer and less invasive treatment method will be established through the continued advancement and innovation of interventional endoscopy techniques.2021年07月, World journal of gastrointestinal oncology, 13(7) (7), 684 - 692, 英語, 国際誌研究論文（学術雑誌）
- 2021年07月, Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association, 英語, 国際誌研究論文（学術雑誌）
- 日本消化器内視鏡学会-近畿支部, 2021年07月, 日本消化器内視鏡学会近畿支部例会プログラム・抄録集, 106回, 88 - 88, 日本語肝外門脈閉塞で形成されたCavernous transformationを合併した遠位胆管癌の一例
- PURPOSE: The risk factors and clinical characteristics of ICI-induced immune-mediated hepatotoxicity (IMH) are not fully understood. Thus, the present study sought to clarify the clinical features of IMH. METHODS: All patients treated with ICIs between September 2014 and April 2019 at our institution were included. Clinical data were retrospectively collected from medical records. The frequency of grade ≥ 2 liver damage, clinical characteristics, and risk factors for developing IMH were examined. RESULTS: Overall, 250 patients (median age 71 years; range 30-87 years; 202 males and 48 females) were included in the analyses. Forty-five patients had elevated transaminase levels (> threefold the upper limit of normal). Of these, 21 were considered to have IMH. The remaining 24 patients had other causes of elevated transaminase levels. Steroids were administered to 13/21 patients with IMH. Although all patients exhibited improvement, IMH was not associated with the anticancer efficacy of the ICIs or OS. A multivariable analysis revealed that IMH was significantly associated with malignant melanoma (odds ratio [OR] 11.6; 95% confidence interval [CI] 3.5-38.0; P = 0.0002) and ipilimumab-nivolumab combination therapy (OR 61.2; 95% CI 7.9-1275.3; P < 0.0001). CONCLUSION: Immune-mediated hepatotoxicity occurred in 9.5% of patients treated with ICIs. Appropriate therapeutic interventions are important to avoid affecting the patient's prognosis, and accurate diagnosis of IMH is essential for this purpose. The frequency of IMH varied according to the type of cancer and the drug used, and was significantly higher in patients with malignant melanoma and in patients given ipilimumab-nivolumab combination therapy.2021年06月, Journal of cancer research and clinical oncology, 147(6) (6), 1747 - 1756, 英語, 国際誌研究論文（学術雑誌）
- A 78-year-old man who underwent right nephrectomy for renal cell carcinoma (RCC) 18 years ago visited our hospital complaining of abdominal pain. Imaging revealed that the pancreatic head tumor obstructed the Santorini duct. We suspected a pancreatic intraductal tumor, such as an intraductal tubulopapillary neoplasm or intraductal papillary mucinous neoplasm. Thus, the patient underwent subtotal stomach-preserving pancreaticoduodenectomy. Pathological findings confirmed the diagnosis of metastatic RCC. Herein, we report a case of pancreatic metastasis of an RCC that presented with a tumor in the pancreatic duct.2021年06月, Clinical journal of gastroenterology, 14(3) (3), 905 - 909, 英語, 国内誌研究論文（学術雑誌）
- Highlight Atalla and colleagues present a novel dumbbell-shaped fully covered self-expandable metal stent which, with its anti-migration property and relatively lower cost, is a feasible and cost-effective option as an alternative to lumen-apposing metal stents for endoscopic ultrasound-guided transduodenal gallbladder drainage for acute cholecystitis in patients who are ineligible for surgery.2021年05月, Journal of hepato-biliary-pancreatic sciences, 28(5) (5), e19-e20, 英語, 国内誌研究論文（学術雑誌）
- (一社)日本消化器内視鏡学会, 2021年04月, Gastroenterological Endoscopy, 63(Suppl.1) (Suppl.1), 892 - 892, 日本語胆道出血に対する内視鏡治療の現状と課題 特に肝細胞癌からの胆道出血に関して
- (一社)日本消化器内視鏡学会, 2021年04月, Gastroenterological Endoscopy, 63(Suppl.1) (Suppl.1), 907 - 907, 日本語EUS-hepaticogastrostomyにおけるトラブルを未然に回避するためのダブルガイドワイヤー法
- (一社)日本消化器内視鏡学会, 2021年04月, Gastroenterological Endoscopy, 63(Suppl.1) (Suppl.1), 980 - 980, 日本語内視鏡的乳頭切除術を行った早期十二指腸乳頭部腫瘍の予後に関する検討
- INTRODUCTION: In patients with malignant distal bile duct obstruction and normal gastrointestinal anatomy, endoscopic ultrasound-guided choledochoduodenostomy (EUS-CDS) is indicated when endoscopic retrograde cholangiopancreatography (ERCP) fails. The ERCP drainage route passes through the tumor, whereas the EUS-CDS route does not. Therefore, EUS-CDS is expected to have a longer stent patency than ERCP. However, for first-line biliary drainage, it remains unclear whether EUS-CDS or ERCP is superior in terms of stent patency. To reduce the frequency of highly adverse events (AEs) such as bile peritonitis or stent migration following EUS-CDS, we developed an antimigration metal stent with a thin delivery system for tract dilatation. This study is designed to assess whether EUS-CDS with this novel stent is superior to ERCP with a traditional metal stent in terms of stent patency when the two techniques are used for first-line drainage of malignant distal biliary obstruction. METHODS/DESIGN: This study is a multicenter single-blinded randomized controlled trial (RCT) involving 95 patients in four tertiary centers. Patients with malignant distal biliary obstruction that is unresectable or presents a very high surgical risk and who pass the inclusion and exclusion criteria will be randomized to EUS-CDS or ERCP in a 1:1 proportion. The primary endpoint is the stent patency rate 180 days after stent insertion. Secondary outcomes include the rates of technical success, clinical success, technical success in cases not requiring fistulous-tract dilation (only EUS-CDS group), procedure-related AEs, re-intervention success, patients receiving post-drainage chemotherapy, procedure time, and overall survival time. DISCUSSION: If EUS-CDS is superior to ERCP in terms of stent patency and safety for the first-line drainage of malignant distal biliary obstruction, it is expected that the first-line drainage method will be changed from ERCP to EUS-CDS, and that interruption of chemotherapy due to stent dysfunction can be avoided. TRIAL REGISTRATION: University Hospital Medical Information Network Clinical Trials Registry (UMIN-CTR), ID: UMIN000041343. Registered on August 6, 2020. https://upload.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000047201Version number: 1.2, December 7, 2020.2021年03月, Medicine, 100(12) (12), e25268, 英語, 国際誌研究論文（学術雑誌）
- BACKGROUND: Surgical resection of intraductal papillary mucinous neoplasm (IPMN) is strongly recommended for patients exhibiting high-risk stigmata (HRS). However, determining surgical indications for elderly patients with comorbidities is challenging, as clinical outcomes are not well characterized. This multicenter observational study elucidated the clinical outcomes of patients with IPMN exhibiting HRS who did not undergo surgery. METHODS: This study enrolled 101 IPMN patients exhibiting HRS with follow-up observations at 11 hospitals in Japan (2011-2016). The median observation period was 37 months (maximum: 86 months). Primary outcomes were estimated 5-year overall survival (OS) and disease-specific survival (DSS). Survival was also stratified based on HRS features. RESULTS: Of 101 patients, 32 (31.7%) had the main pancreatic duct (MPD) measuring ≥ 10 mm and 80 (79.2%) had mural nodules measuring ≥ 5 mm. The estimated 5-year OS and DSS were 74% and 91%, respectively. In the stratified analysis, the co-presence of MPD ≥ 10 mm and mural nodules ≥ 5 mm or mural nodule ≥ 10 mm were related to worse 5-year DSS (MPD ≥ 10 mm and mural nodules ≥ 5 mm vs other characteristics: 60% vs 95%, log-rank test: p = 0.049; mural nodules ≥ 10 mm vs < 10 mm: 77% vs 95%, log-rank test: p = 0.003). CONCLUSIONS: The estimated 5-year DSS of conservatively managed IPMN patients with mural nodules and main duct dilation was 91%. Only IPMN patients with plural HRS or large nodule formation might have an increased mortality risk. This is an important insight that can help facilitate appropriate clinical decision-making, especially in the elderly or high-surgical risk IPMN patients.2021年03月, Journal of gastroenterology, 56(3) (3), 285 - 292, 英語, 国内誌研究論文（学術雑誌）
- 日本消化器病学会-近畿支部, 2021年02月, 日本消化器病学会近畿支部例会プログラム・抄録集, 114回, 59 - 59, 日本語膵管内腫瘍様の形態を呈した腎癌膵臓転移症例の一例
- 2021年02月, Endoscopy, 53(2) (2), E52-E53, 英語, 国際誌研究論文（学術雑誌）
- 2021年02月, VideoGIE : an official video journal of the American Society for Gastrointestinal Endoscopy, 6(2) (2), 87 - 89, 英語, 国際誌研究論文（学術雑誌）
- Drug-induced pancreatitis is often mild to moderate in severity, but severe and even fatal cases can occur. Here, we report a 74-year-old woman undergoing chemotherapy for recurrent renal cell carcinoma, who presented with abdominal pain after administration of pazopanib following nivolumab and was diagnosed with severe acute pancreatitis. Administration of methylprednisolone and conservative treatment were initiated, but clinical findings and laboratory tests rapidly worsened. When she died, an autopsy was performed. The autopsy findings suggested the possibility of pancreatitis as immune-related adverse events. To the best of our knowledge, no fatal cases of acute pancreatitis due to nivolumab or pazopanib have been reported. We considered that the effects of nivolumab were sustained in the pancreas, and pazopanib administration might have worsened the toxicity.2021年01月, Pancreatology : official journal of the International Association of Pancreatology (IAP) ... [et al.], 21(1) (1), 21 - 24, 英語, 国際誌研究論文（学術雑誌）
- BACKGROUND: Intraductal papillary mucinous neoplasm (IPMN) of the pancreas is associated with acute pancreatitis (AP) in some cases, however its causes have not been fully elucidated. We investigated the association of the incidence of AP with epithelial subtypes and pancreatic volume in IPMN. METHODS: This retrospective study included 182 consecutive surgically resected IPMN patients between January 2000 and December 2018. The relationship between the incidence of AP and epithelial subtypes of IPMN and pancreatic volume was investigated. Epithelial subtypes of IPMN were classified into gastric (G type: N = 116), intestinal (I type: N = 49), pancreatobiliary (PB type: N = 14), and oncocytic types (O type: N = 3). Pancreatic volume of the contrast-enhanced computed tomography scan was measured using Ziostation2 software. Histological pancreatic parenchymal atrophy was also evaluated. RESULTS: AP occurred more frequently in I-types (I-type vs. G-type, 22.4% [11/49] vs 3.4% [4/116], P = 0.003) and PB-types (PB type vs. G-type, 35.7% [5/14] vs. 3.4% [4/116], P = 0.007) in comparison with G-types, which constituted the majority of the resected IPMNs. AP occurred more frequently in I-type patients with high pancreatic volumes (I-type with high pancreatic volume vs. I-type with low pancreatic volume, 37.0% [10/27] vs. 4.7% [1/21], P = 0.02). However, histological atrophy did not show an additional influence on the association between the incidence of AP and epithelial subtypes. The elevation of serum pancreatic enzymes was not significantly related to epithelial subtypes. CONCLUSION: Epithelial subtypes and the degree of pancreatic volume may be closely associated with the incidence of AP in IPMN.2021年01月, Pancreatology : official journal of the International Association of Pancreatology (IAP) ... [et al.], 21(1) (1), 138 - 143, 英語, 国際誌研究論文（学術雑誌）
- 2021年01月, VideoGIE : an official video journal of the American Society for Gastrointestinal Endoscopy, 6(1) (1), 19 - 21, 英語, 国際誌研究論文（学術雑誌）
- A 60-year-old male visited a previous hospital with upper abdominal pain. He was diagnosed with localized mild acute pancreatitis. Three months later, abdominal contrast-enhanced computed tomography showed focal parenchymal atrophy of the pancreas with distal pancreatic duct dilation. No obvious solid mass could be found at the site of the pancreatic duct stenosis on imaging examinations. Endoscopic retrograde pancreatography showed focal mild stenosis with distal pancreatic duct dilation in the tail of the pancreas. Carcinoma in situ of the pancreas was strongly suspected, especially based on the presence of focal atrophy of the pancreas around the site of stenosis of the main pancreatic duct and the distal pancreatic duct dilation. Laparoscopic distal pancreatectomy was performed. Histologically, high-grade pancreatic intraepithelial neoplasia was found in the epithelium of the stenotic main pancreatic duct and its branches. This case suggests that localized acute pancreatitis and focal atrophy of the pancreas with distal dilation of the pancreatic duct could be important clinical manifestations of pancreatic carcinoma in situ.2020年12月, Clinical journal of gastroenterology, 13(6) (6), 1338 - 1342, 英語, 国内誌研究論文（学術雑誌）
- 2020年11月, Digestive and liver disease : official journal of the Italian Society of Gastroenterology and the Italian Association for the Study of the Liver, 英語, 国際誌研究論文（学術雑誌）
- A 66-year-old Japanese man was referred to our hospital with multiple giant liver cysts. The cysts had already been detected as multiple 3-cm cysts with small nodules at another hospital 12 years prior to this presentation. The cysts were diagnosed as an intraductal papillary neoplasms of the bile duct (IPNB) occupying the right lobe of the liver. Extended right lobectomy was performed. Based on the pathological findings, the tumor was diagnosed to be an oncocytic-type IPNB with minimal invasion. This experience suggests that the progression of IPNBs occur relatively slowly. The present case might provide important information for understanding the natural history of IPNBs.2020年11月, Internal medicine (Tokyo, Japan), 59(22) (22), 2879 - 2883, 英語, 国内誌研究論文（学術雑誌）
- 2020年11月, Digestive endoscopy : official journal of the Japan Gastroenterological Endoscopy Society, 32(7) (7), 1114 - 1114, 英語, 国際誌
- 日本消化器病学会-近畿支部, 2020年10月, 日本消化器病学会近畿支部例会プログラム・抄録集, 113回, 84 - 84, 日本語胆嚢癌との鑑別が困難であったIgG4関連硬化性胆嚢炎の一例
- 日本消化器病学会-近畿支部, 2020年10月, 日本消化器病学会近畿支部例会プログラム・抄録集, 113回, 84 - 84, 日本語胆嚢癌との鑑別が困難であったIgG4関連硬化性胆嚢炎の一例
- Wiley, 2020年10月, Journal of Gastroenterology and Hepatology, 35(10) (10), 1667 - 1667研究論文（学術雑誌）
- 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.2020年09月, Cancers, 12(9) (9), 英語, 国際誌研究論文（学術雑誌）
- Background and Aims: Imaging tools for predicting pancreatic atrophy after steroid therapy in autoimmune pancreatitis (AIP) have not been established. As delayed equilibrium-phase contrast enhancement in computed tomography (CE-CT) may reflect interstitial fibrosis, we evaluated the ability of equilibrium-phase CT imaging for predicting pancreatic atrophy. Methods: Forty-six steroid-treated AIP patients who underwent contrast-enhanced CT at our university hospital were included in this retrospective study. CT attenuation (Hounsfield units [HU]) values in noncontrast images (NC) and equilibrium-phase images (EP) and the differences in HU values between NC and EP images (SUB) were measured. Pancreatic volume was measured in CE-CT before (Volpre) and after (Volpost) steroid therapy. The volume reduction rate was calculated. The relationships of CT values with pancreatic atrophy, Volpost, volume reduction rate, and diabetes exacerbation were investigated. Results: CT values in the EP and SUB images before steroid therapy were associated with pancreatic atrophy after steroid therapy (atrophy vs nonatrophy 114.5 ± 12.8 vs 99.5 ± 11.1, P = 0.0002; 70.9 ± 14.72 vs 57.2 ± 13.1, P = 0.003, respectively), but CT values in NC images were not (P = 0.42). CT values in EP and SUB images before steroid therapy were correlated with Volpost (EP images r = -0.70, P = 0.002; SUB images r = -0.68, P = 0.03) and volume reduction rate after steroid therapy (EP images: r = -0.55, P < 0.0001; SUB images r = -0.45, P = 0.002). Diabetes exacerbation was associated with higher EP and SUB values (P = 0.009 and P = 0.04, respectively). Conclusion: Equilibrium-phase contrast CT imaging may facilitate prediction of pancreatic atrophy after steroid therapy in AIP.2020年08月, JGH open : an open access journal of gastroenterology and hepatology, 4(4) (4), 677 - 683, 英語, 国際誌研究論文（学術雑誌）
- In this study, we assessed a series of our cases in which endoscopic self-expandable metal stents (SEMSs) were used to treat malignant afferent loop obstruction (ALO) that arose after pancreaticoduodenectomy (PD). We retrospectively examined the records of 7 patients who underwent endoscopic SEMS placement for malignant ALO following PD. Clinical success was achieved in all cases. The median procedure time was 30 min (range, 15-50 min). There were no cases of stent occlusion, and no procedure-related adverse events were encountered. All patients died of their primary disease, and the median overall survival period was 155 days (range, 96-374 days). A re-intervention involving endoscopic ultrasound-guided hepaticogastrostomy combined with antegrade stenting was performed for obstructive jaundice and acute cholangitis in 1 case. In conclusion, endoscopic SEMS placement may be an effective and safe treatment for malignant ALO that arises after PD.2020年07月, Clinical endoscopy, 53(4) (4), 491 - 496, 英語, 国際誌
- A 60-year-old female was admitted to hospital with a continuous fever, a decreased appetite, and abdominal pain. Laboratory tests showed an elevated peripheral leukocyte count (13,800/μl) and increased C-reactive protein (19.1 mg/dl) and carbohydrate antigen 19-9 (4057 U/ml) levels. Abdominal contrast-enhanced computed tomography showed multiple bulky hypovascular nodules in the liver, swelling of the paraaortic lymph nodes, and a hypovascular mass (diameter 3.0 cm) in the pancreatic body. The serum concentrations of granulocyte colony-stimulating factor (G-CSF) and interleukin-6 were 172 pg/μl and 541 pg/µl, respectively. Liver biopsy specimens revealed an adenosquamous carcinoma, which was positively immunostained for G-CSF. We diagnosed the patient with G-CSF-producing pancreatic cancer with multiple metastases. Four courses of gemcitabine with dexamethasone and one course of nab-paclitaxel and gemcitabine were administered. Although the pancreatic tumor and paraaortic lymph node metastases decreased in size, the liver metastases continued to grow. The patient died 4 months after the diagnosis of pancreatic cancer. An autopsy resulted in the tumor being diagnosed as poorly differentiated adenosquamous pancreatic carcinoma, which was histopathologically G-CSF-positive. Although G-CSF-producing pancreatic adenosquamous carcinomas are extremely rare, they have been encountered more frequently in recent years. In such cases, chemotherapy combined with dexamethasone might be effective at temporarily improving the patient's condition.2020年06月, Clinical journal of gastroenterology, 13(3) (3), 448 - 454, 英語, 国内誌研究論文（学術雑誌）
- 2019年11月, Endoscopy, 51(11) (11), E327-E328, 英語, 国際誌研究論文（学術雑誌）
- 2019年10月, Endoscopy, 51(10) (10), E303-E304, 英語, 国際誌研究論文（学術雑誌）
- 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.2019年09月, Journal of gastroenterology and hepatology, 34(9) (9), 1648 - 1655, 英語, 国際誌研究論文（学術雑誌）
- 2019年07月, Digestive endoscopy : official journal of the Japan Gastroenterological Endoscopy Society, 31(4) (4), 465 - 465, 英語, 国際誌
- Eosinophilic cholangitis (EC) is an uncommon, benign, self-limiting disease, which typically causes bile duct stricture with eosinophil infiltration. We report the case of a 70-year-old woman who presented with abdominal pain diagnosed with EC after treatment for eosinophilic esophagitis. All previous reported cases of EC had bile duct stricture seen on magnetic resonance cholangiopancreatography or cholangiogram during endoscopic retrograde cholangiopancreatography, but only wall thickness of the common bile duct was noted in our case. Although rare, EC should be considered when wall thickening of the bile duct is observed, even without stricture.2019年06月, ACG case reports journal, 6(6) (6), e00099, 英語, 国際誌
- 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.2019年04月, Pancreatology : official journal of the International Association of Pancreatology (IAP) ... [et al.], 19(3) (3), 424 - 428, 英語, 国際誌研究論文（学術雑誌）
- BACKGROUND: Endoscopic papillectomy (EP) for benign ampullary neoplasms could be a less-invasive alternative to pancreatoduodenectomy (PD). There are some problems and limitations with EP. The post-EP resection margins of ampullary tumors are often positive or uncertain because of the burning effect of EP. The clinical outcomes of resected margin positive or uncertain cases after EP remain unknown. AIM: To investigate the clinical outcomes of resected margin positive or uncertain cases after EP. METHODS: Between January 2007 and October 2018, all patients with ampullary tumors who underwent EP at Kobe University Hospital were included in this study. The indications for EP were as follows: adenoma, as determined by preoperative endoscopic biopsy, without bile/pancreatic duct extension, according to endoscopic ultrasound or intraductal ultrasound. The clinical outcomes of resected margin positive or uncertain cases after EP were retrospectively investigated. RESULTS: Of the 45 patients, 29 were male, and 16 were female. The mean age of the patients was 65 years old. Forty-one patients (89.5%) underwent en bloc resection, and 4 patients (10.5%) underwent piecemeal resection. After EP, 33 tumors were histopathologically diagnosed as adenoma, and 12 were diagnosed as adenocarcinoma. The resected margins were positive or uncertain in 24 patients (53.3%). Of these cases, 15 and 9 were diagnosed as adenoma and adenocarcinoma, respectively. Follow-up observation was selected for all adenomas and 5 adenocarcinomas. In the remaining 4 adenocarcinoma cases, additional PD was performed. Additional PD was performed in 4 cases, and residual carcinoma was found after the additional PD in 1 of these cases. In the follow-up period, local tumor recurrence was detected in 3 cases. Two of these cases involved primary EP-diagnosed adenoma. The recurrent tumors were also adenomas detected by biopsy. The remaining case involved primary EP-diagnosed adenocarcinoma. The recurrent tumor was also an adenocarcinoma. All of the recurrent tumors were successfully treated with argon plasma coagulation (APC). There was no local or lymph node recurrence after the APC. The post-APC follow-up periods lasted for 57.1 to 133.8 mo. No ampullary tumor-related deaths occurred in all patients. CONCLUSION: Resected margin positive or uncertain cases after EP could be managed by endoscopic treatment including APC, even in cases of adenocarcinoma. EP could become an effective less-invasive first-line treatment for early stage ampullary tumors.2019年03月, World journal of gastroenterology, 25(11) (11), 1387 - 1397, 英語, 国際誌研究論文（学術雑誌）
- PURPOSE: IgG4-related disease involves various organs including the pituitary and pancreas. The prevalence of IgG4-related hypophysitis is relatively rare compared with IgG4-related pancreatitis (autoimmune pancreatitis). Although several cases demonstrating both autoimmune pancreatitis and hypophysitis have been reported, the prevalence of IgG4-related hypophysitis in patients with autoimmune pancreatitis remains unknown. This study aimed at screening for IgG4-related hypophysitis to accurately determine its prevalence in patients with autoimmune pancreatitis. METHODS: In this cohort study, we screened IgG4-related hypophysitis via pituitary magnetic resonance imaging (MRI) and endocrinological examination in 27 patients who were undergoing follow-up for autoimmune pancreatitis at Kobe University Hospital between 2014 and 2018. RESULTS: Among 27 patients with autoimmune pancreatitis, 5 patients exhibited morphological abnormalities in the pituitary (18.5%). Among them, one patient (3.7%) met the criteria for hypophysitis with an enlarged pituitary and stalk concomitant with hypopituitarism. After glucocorticoid treatment, the enlarged pituitary shrank and became empty sella during the clinical course. Four patients (14.8%) revealed empty sella without obvious pituitary dysfunction. Four of 5 patients with morphological pituitary abnormalities showed multiple organ involvement in addition to pancreatic and pituitary involvement. Accordingly, multiple organ involvement was more prevalent in patients with morphological pituitary abnormalities (80%) compared to those without (48%). CONCLUSIONS: Although a large-scale study is necessary to validate these results, these data suggest that the prevalence of hypophysitis in patients with autoimmune pancreatitis may be underestimated. Based on our findings, we recommend screening for hypophysitis, especially in patients with multiple organ involvement.2019年02月, Pituitary, 22(1) (1), 54 - 61, 英語, 国際誌研究論文（学術雑誌）
- 2018年08月, Gastrointestinal endoscopy, 88(2) (2), 405 - 406, 英語, 国際誌研究論文（学術雑誌）
- 2018年08月, Endoscopy, 50(8) (8), E229-E230, 英語, 国際誌研究論文（学術雑誌）
- 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.2018年06月, Pancreatology : official journal of the International Association of Pancreatology (IAP) ... [et al.], 18(4) (4), 399 - 406, 英語, 国際誌研究論文（学術雑誌）
- 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.2018年03月, Biochemical and biophysical research communications, 497(3) (3), 903 - 907, 英語, 国際誌研究論文（学術雑誌）
- (一財)日本消化器病学会, 2017年09月, 日本消化器病学会雑誌, 114(臨増大会) (臨増大会), A689 - A689, 日本語Innovative therapeutic endoscopy 膵仮性嚢胞・感染性WONに対する内視鏡的治療 Walled off necrosisに対する内視鏡的step-up approachの妥当性の検討
- (一社)日本消化器内視鏡学会, 2017年09月, Gastroenterological Endoscopy, 59(Suppl.2) (Suppl.2), 2103 - 2103, 日本語Innovative therapeutic endoscopy 膵仮性嚢胞・感染性WONに対する内視鏡的治療 Walled off necrosisに対する内視鏡的step-up approachの妥当性の検討
- RATIONALE: The analytical stability and throughput of biomarker assays based on dried serum spots (DSS) are strongly dependent on the extraction process and determination method. In the present study, an on-line system based on supercritical fluid extraction-supercritical fluid chromatography coupled with tandem mass spectrometry (SFE-SFC/MS/MS) was established for analyzing the levels of disease biomarkers in DSS. METHODS: The chromatographic conditions were investigated using the ODS-EP, diol, and SIL-100A columns. Then, we optimized the SFE-SFC/MS/MS method using the diol column, focusing on candidate biomarkers of oral, colorectal, and pancreatic cancer that were identified using liquid chromatography (LC)/MS/MS. RESULTS: By using this system, four hydrophilic metabolites and 17 hydrophobic metabolites were simultaneously detected within 15 min. In an experiment involving clinical samples, PC 16:0-18:2/16:1-18:1 exhibited 93.8% sensitivity and 64.3% specificity, whereas PC 17:1-18:1/17:0-18:2 showed 81.3% sensitivity and 92.9% specificity for detecting oral cancer. In addition, assessments of the creatine levels demonstrated 92.3% sensitivity and 78.6% specificity for detecting colorectal cancer. CONCLUSIONS: The results of this study indicate that our method has great potential for clinical diagnosis and would be suitable for large-scale screening. Copyright © 2017 John Wiley & Sons, Ltd.2017年05月, Rapid communications in mass spectrometry : RCM, 31(10) (10), 886 - 894, 英語, 国際誌研究論文（学術雑誌）
- History of Post-Endoscopic Retrograde Cholangiopancreatography Pancreatitis and Acute Pancreatitis as Risk Factors for Post-ERCP Pancreatitis.BACKGROUND: Previous pancreatitis is a definite patient-related risk factor for pancreatitis after endoscopic retrograde cholangiopancreatography (post-ERCP pancreatitis: PEP). However, the effects of differences in the history of PEP and acute pancreatitis on the occurrence of PEP have not been fully investigated. We examined the relationship between previous PEP or previous acute pancreatitis and procedural factors associated with PEP. METHODS: Clinical data on 1,334 consecutive patients undergoing ERCP between April 2006 and June 2010 were collected. A multivariate logistic regression analysis was conducted to assess the relationship between PEP and the cannulation time (<15 min vs. ≥15 min) or total procedure time (<30 min vs. ≥30 min) according to previous pancreatitis (previous PEP: pPEP or previous acute pancreatitis: pAP), with adjustments for clinical characteristics. RESULTS: Longer cannulation times (≥15 min) correlated with the occurrence of PEP in the pPEP group (OR=2.97; 95% CI=1.10 to 8.43, P=0.03) and in patients without previous pancreatitis (non-preP group) (OR=2.43; 95% CI=1.41 to 4.14, P= 0.002), but not in the pAP group (OR=2.78; 95% CI=0.50 to 22.42, P= 0.25). In contrast, longer procedure times correlated with the occurrence of PEP in the pAP group (OR=3.93; 95% CI=1.11 to 16.5, P= 0.03), but not in the pPEP group (OR=2.79; 95% CI=0.92 to 9.18, P= 0.068) or non-preP group (OR=0.71; 95% CI=0.39 to 1.24, P= 0.23). CONCLUSIONS: A higher risk of PEP with previous PEP was associated with longer cannulation times, whereas a higher risk of PEP with previous acute pancreatitis was associated with longer procedure times.2017年05月, The Kobe journal of medical sciences, 63(1) (1), E1-E8, 英語, 国内誌研究論文（学術雑誌）
- (一財)日本消化器病学会, 2017年03月, 日本消化器病学会雑誌, 114(臨増総会) (臨増総会), A392 - A392, 日本語造影EUSを用いた膵癌の血流動態と化学療法感受性における検討
- Elsevier {BV}, 2017年01月, Pancreatology, 17(1) (1), 123 - 129, 英語[査読有り]研究論文（学術雑誌）
- BACKGROUND/OBJECTIVES: The recent guideline for intraductal papillary mucinous neoplasms (IPMNs) focuses on morphological features of the lesion as signs of malignant transformation, but ignores the background pancreatic parenchyma, including features of chronic pancreatitis (CP), which is a risk factor for pancreatic malignancies. Endoscopic ultrasonography frequently reveals evidence of CP (EUS-CP findings) in the background pancreatic parenchyma of patients with IPMNs. Therefore, we investigated whether background EUS-CP findings were associated with malignant IPMN. METHODS: The clinical data of 69 consecutive patients with IPMNs who underwent preoperative EUS and surgical resection between April 2010 and October 2014 were collected prospectively. The association of EUS-CP findings (total number of EUS-CP findings; 0 vs. ≥1) with invasive IPMN was examined. The association of EUS-CP findings with pathological changes of the background pancreatic parenchyma (atrophy/inflammation/fibrosis) was also examined. RESULTS: Among patients with EUS-CP findings, invasive intraductal papillary mucinous carcinoma (IPMC) was significantly more frequent than among patients without EUS-CP findings (42.5% [17/40] vs. 3.4% [1/29], p = 0.0002). In addition, patients with EUS-CP findings had higher grades of pancreatic atrophy and inflammation than patients without EUS-CP findings (atrophy: 72.5% [29/40] vs. 34.5% [10/29], p = 0.003; inflammation: 45.0% [18/40] vs. 20.7% [6/29], p = 0.04). CONCLUSIONS: In IPMN patients, detection of EUS-CP findings in the background pancreatic parenchyma was associated with a higher prevalence of invasive IPMC. Accordingly, EUS examination should not only assess the morphological features of the lesion itself, but also EUS-CP findings in the background parenchyma.2017年, Oncology, 93 Suppl 1, 61 - 68, 英語, 国際誌研究論文（学術雑誌）
- AIM: To examine a novel screening method for pancreatic cancer involving gas chromatography/mass spectrometry and liquid chromatography/mass spectrometry-based metabolomics analysis. MATERIALS & METHODS: Sera from pancreatic cancer patients (n = 59) and healthy volunteers (n = 59) were allocated to the training set or validation set. Serum metabolome analysis was carried out using our multiplatform metabolomics system. A diagnostic model was constructed using a two-phase screening method that was newly advocated. RESULTS: When the training set was used, the constructed diagnostic model exhibited high sensitivity (100%) and specificity (80%) for pancreatic cancer. When the validation set was used, the model displayed high sensitivity (84.1%) and specificity (84.1%). CONCLUSION: We successfully developed a diagnostic model for pancreatic cancer using a multiplatform serum metabolomics system.2016年06月, Biomarkers in medicine, 10(6) (6), 577 - 86, 英語, 国際誌研究論文（学術雑誌）
- In 2010, a 39-year-old woman presented with a cystic lesion, 16 mm in diameter, in the tail of the pancreas. Regular follow-ups were conducted to monitor this lesion; its diameter was found to increase to 45 mm in 2013. Thus, the patient was admitted to our hospital for further examination and treatment. Abdominal US, abdominal contrast-enhanced CT, and MRI showed a cystic lesion of 45 mm in diameter in the tail of the pancreas, which had internal septae and mural nodules inside. EUS revealed a cyst-in-cyst-like structure, with a thickened cystic wall along the entire circumference. Thus, distal pancreatectomy and splenectomy were performed on the basis of a diagnosis of mucinous cystic neoplasm. Histopathological examination of a resected specimen showed that the lesion comprised a substantial component of red-brown tone, with adjacent cystic components. The final diagnosis was an epidermoid cyst in an intrapancreatic accessory spleen.2015年10月, Nihon Shokakibyo Gakkai zasshi = The Japanese journal of gastro-enterology, 112(10) (10), 1858 - 67, 日本語, 国内誌研究論文（学術雑誌）
- 日本膵臓学会, 2015年05月, 膵臓, 30(3) (3), 443 - 443, 日本語
- Afferent loop obstruction caused by cancer recurrence after pancreaticoduodenectomy (PD) can be managed by either surgical or nonsurgical treatment. The general condition of patients with recurrent pancreaticobiliary cancer is often not good enough for them to undergo surgery, so less invasive nonsurgical treatment is desirable. We report a case of a 66-year-old male who had undergone PD for pancreatic head adenocarcinoma 10 months previously and who presented at our hospital with fever and jaundice due to afferent loop obstruction caused by pancreatic cancer recurrence. An endoscopic self-expandable metal stent (SEMS) was placed for afferent loop obstruction without any complications. He quickly recovered after SEMS placement. He retained a good quality of life by receiving chemotherapy until his death due to cancer progression. Our case indicates that this method could be an easy, effective, safe, and less invasive treatment, which may confer a better quality of life for patients with afferent loop obstruction due to cancer recurrence after PD.2015年04月, Clinical journal of gastroenterology, 8(2) (2), 103 - 7, 英語, 国内誌研究論文（学術雑誌）
- (一社)日本消化器内視鏡学会, 2014年09月, Gastroenterological Endoscopy, 56(Suppl.2) (Suppl.2), 3052 - 3052, 日本語膵腫瘤性病変における造影ハーモニックEUSの有用性
- Factors related to shift from hepatic borderline lesion to overt HCC diagnosed by CT.BACKGROUND/AIMS: Factors contributing to the shift from the hepatic borderline lesion to overt hepatocellular carcinoma (HCC) were investigated. METHODOLOGY: Ninety-five borderline nodules from 69 patients were followed-up for 6-55 (median 24) months. The borderline lesion was diagnosed when the CT image demonstrated low density in the portal phase and lacked enhancement in the arterial phase. RESULTS: The shift to overt HCC was seen in 32 nodules from 27 patients. Using multivariate analysis, only size was a significant factor contributing to the shift to overt HCC (p = 0.009). The cumulative incidence of the shift to overt HCC was higher in nodules of ≥13 mm in size than in those of < 13 mm (p = 0.034). Among nodules of ≥13 mm, nodules showing iso density in the arterial phase and low density in the portal phase had a higher cumulative incidence of the shift to overt HCC than those showing low density in the arterial and portal phases on CT (p=0.007). CONCLUSIONS: In hepatic borderline nodules diagnosed by CT, greater size, and iso density in the arterial phase and low density in the portal phase may be risk factors associated with the shift to overt HCC.2014年09月, Hepato-gastroenterology, 61(134) (134), 1680 - 7, 英語, 国際誌研究論文（学術雑誌）
- 日本膵臓学会, 2014年06月, 膵臓, 29(3) (3), 579 - 579, 日本語
- Background/objectives: Morphological types and mucin protein expressions classify intraductal papillary mucinous neoplasms (IPMNs). Main duct (MD)-IPMN mostly consists of intestinal type (I-type), which expresses MUC2. Branch duct (BD)-IPMN mostly consists of gastric type (G-type), which does not express MUC2. However, the definition of mixed-type IPMN has yet to be clarified and it contains various histological types. The aim of this study was to investigate the relationship between MUC2 expression and the presence of high-grade dysplasia (HGD) and invasive carcinoma, especially in mixed-type IPMN. Methods: This retrospective study included 101 consecutive patients with surgically resected IPMNs between April 2001 and October 2012. All patients were morphologically classified into four distinct types (I-type, G-type, PB-type: pancreatobilliary, O-type: oncocytic) and immunohistochemical reactivity of various anti-mucin antibodies were investigated. Results: According to the classification of the 2012 international guidelines, the numbers (and histomorphological types: I/G/PB/O) of MD, mixed-type, and BD-IPMNs were 16 (12/4/0/0), 45 (16/28/1/0), and 40 (0/38/1/1). Prevalence of MUC2 expression in MD, mixed-type, and BD-IPMNs were 75% (12/16), 36% (16/45), and 0% (0/40). In mixed-type IPMN, the prevalence of HGD and/or invasive carcinoma in MUC2-positive IPMN was significantly higher than that of MUC2-negative IPMN (HGD + invasive carcinoma: 88% vs. 38%, p = 0.0017; invasive carcinoma: 50% vs. 21%, p = 0.042). Multivariate analysis showed that MUC2 expression is an independent predictive factor of HGD and invasive carcinoma in mixed IPMN (odds ratio 14.6, 95% CI 2.5-87.4, p = 0.003). Conclusions: In mixed-type IPMN, MUC2 expression clearly identified HGD and invasive carcinoma and may provide most appropriate surgical indication. Copyright (C) 2013, IAP and EPC. Published by Elsevier India, a division of Reed Elsevier India Pvt. Ltd. All rights reserved.KARGER, 2013年11月, PANCREATOLOGY, 13(6) (6), 583 - 588, 英語[査読有り]研究論文（学術雑誌）
- BACKGROUND: Endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) is an accurate method for cytological confirmation of pancreatic malignancy, but peritoneal dissemination caused by EUS-FNA could be a matter of concern because it may lead to poorer prognosis. Our aim was to estimate the risk of peritoneal carcinomatosis by EUS-FNA for pancreatic cancer. METHODS: Two hundred and seventeen patients with cytopathologically proven pancreatic cancer in a tertiary referral center were retrospectively reviewed. They were divided into two groups: 161 patients who underwent endoscopic retrograde cholangiopancreatography (ERCP) alone (ERCP group), and 56 patients who had ever undergone EUS-FNA (EUS-FNA group). Peritoneal carcinomatosis was diagnosed by computed tomography and/or cytology during follow-up. Hazard ratios of factors including EUS-FNA for the development of peritoneal carcinomatosis were analyzed by the Cox proportional hazard model. RESULTS: There was no significant difference in baseline characteristics between ERCP and EUS-FNA groups. Peritoneal carcinomatosis developed in 14.9 % (24/161) during an average follow-up period of 545 days, and 17.9 % (10/56) during 599 days among ERCP and EUS-FNA group, respectively. The EUS-FNA was not identified as a significant risk factor with hazard ratios (HR) of 1.07 [95 % confidence interval (CI) 0.51-2.25, p = 0.85] by univariate analysis and 1.35 (95 % CI 0.62-2.95, p = 0.45) by multivariate analysis. Nodal involvement (HR 2.19, 95 % CI 1.03-4.63, p = 0.04) and non-resection (HR 2.64, 95 % CI 1.11-6.25, p = 0.03) were shown to be statistically significant risk factors by multivariate analysis. CONCLUSIONS: EUS-FNA for pancreatic cancer did not significantly increase the risk of peritoneal carcinomatosis.2013年08月, Journal of gastroenterology, 48(8) (8), 966 - 72, 英語, 国内誌研究論文（学術雑誌）
- 自己免疫性膵炎は本邦より発信された疾患で,国際的にも広く認知され,疾患概念が広まってきた。本邦では自己免疫性膵炎診断基準および自己免疫性膵炎診療ガイドラインが整備され専門医でなくともエビデンスに基づいた診療が可能である。しかしながら,実臨床においては診断や診療に難渋する症例にしばしば遭遇し,また各専門医あるいは施設によって独自の診療がなされていることも多い。当院では自己免疫性膵炎の診療はガイドラインに従いつつ可能な限りに診療ストラテジーの標準化を図っている。本稿では当院の胆膵専門外来における自己免疫性膵炎の診療の実際を紹介したい。(著者抄録)医学図書出版(株), 2022年11月, 胆と膵, 43(特別号) (特別号), 1385 - 1390, 日本語
- 膵外分泌はコレシストキニン(CCK)などの消化管ホルモンが腺房細胞に存在する受容体に結合することによって起こる。膵外分泌は細胞内Ca2+濃度によって厳格に制御されているが、過剰なCCK刺激が腺房細胞に加わると細胞内Ca2+濃度の恒常性が破綻して膵外分泌不全に陥る。このとき、腺房細胞内ではCCKが受容体に結合することにより、ホスホリパーゼC(PLC)を介して、イノシトール三リン酸(IP3)とジアシルグリセロール(DAG)が産生される。IP3は小胞体からの細胞内Ca2+放出を促し、細胞内Ca2+濃度が持続的な異常高値状態になる。引き続き、膵外分泌不全やNF-κB経路の活性化といった複合的な異常が並行して進行し膵炎に至る。CCK受容体への刺激を細胞内に伝えるPLC epsilon(PLCε)は他臓器において炎症とのかかわりが示唆されているPLCのサブタイプの一つである。われわれはPLCεの膵炎時の機能解析を通じて、膵炎時の腺房細胞における炎症制御機構を検討しており、本稿ではその一端を紹介する。今後も、膵炎の新規治療ターゲットを見出すために膵炎時の腺房細胞内シグナル伝達経路の詳細な解明が期待される。(著者抄録)医学図書出版(株), 2022年08月, 胆と膵, 43(8) (8), 751 - 757, 日本語
- (一社)日本消化器内視鏡学会, 2021年04月, Gastroenterological Endoscopy, 63(Suppl.1) (Suppl.1), 892 - 892, 日本語胆道出血に対する内視鏡治療の現状と課題 特に肝細胞癌からの胆道出血に関して
- (一社)日本消化器内視鏡学会, 2021年04月, Gastroenterological Endoscopy, 63(Suppl.1) (Suppl.1), 907 - 907, 日本語EUS-hepaticogastrostomyにおけるトラブルを未然に回避するためのダブルガイドワイヤー法
- (一社)日本消化器内視鏡学会, 2021年04月, Gastroenterological Endoscopy, 63(Suppl.1) (Suppl.1), 976 - 976, 日本語乳酸リンゲル液の投与によるERCP後膵炎発症予防効果の検討
- (一社)日本消化器内視鏡学会, 2021年04月, Gastroenterological Endoscopy, 63(Suppl.1) (Suppl.1), 980 - 980, 日本語内視鏡的乳頭切除術を行った早期十二指腸乳頭部腫瘍の予後に関する検討
- (一財)日本消化器病学会, 2021年03月, 日本消化器病学会雑誌, 118(臨増総会) (臨増総会), A323 - A323, 日本語治療困難胆管結石に対する電気衝撃波結石破砕術(EHL)の当院における現状と治療成績の検討
- 日本消化器病学会-近畿支部, 2021年02月, 日本消化器病学会近畿支部例会プログラム・抄録集, 114回, 59 - 59, 日本語膵管内腫瘍様の形態を呈した腎癌膵臓転移症例の一例
- 2021年, 日本消化器病学会雑誌(Web), 118治療困難胆管結石に対する電気衝撃波結石破砕術(EHL)の当院における現状と治療成績の検討
- 2021年, 超音波医学 Supplement, 48良性胆膵疾患に対するInterventional EUSの検討
- 2021年, 胆と膵, 42(8) (8)膵癌,膵炎の病態解明と新規治療開発にむけた研究の最前線 膵癌のメタボローム解析によるバイオマーカーと新規治療の開発
- EUS-BDのすべて EUS-BDのトレーニングEUS-BDは経乳頭胆道ドレナージ術が困難な症例に対する代替治療として普及しつつある。しかし偶発症率は決して低くなく、ときに重症化することもあるため、施行医は手技に関する十分な知識と技術を身につけたうえで慎重に実施することが望ましい。トレーニング方法については、公的に定められたものはなく個々の施設の方針に沿って行われているのが現状である。他の内視鏡手技を習得する方法と同様に、教材での学習、ライブセミナーへの参加、専門施設での見学、支援モデルによるハンズオンを活用するのがよい。EUS-BDの支援モデルには、ファントムモデルと動物モデルが報告されている。両モデルの利点や欠点を考慮すると、まずファントムモデルでEUS-BDの各ステップにおける基本的手技を習得してから、動物モデルで実践に近いトレーニングを行っていくような学習段階に合わせた使い分けが推奨される。そして実臨床でEUS-BDを行う際には、指導医の監督下で可能な限り安全な体制をとって実施することが望ましい。(著者抄録)医学図書出版(株), 2021年, 胆と膵, 42(4) (4), 285 - 292, 日本語
- 日本消化器内視鏡学会-近畿支部, 2020年12月, 日本消化器内視鏡学会近畿支部例会プログラム・抄録集, 105回, 62 - 62, 日本語縦隔内膵仮性嚢胞に対し内視鏡的ドレナージが奏功した1例
- (一社)日本膵臓学会, 2020年07月, 膵臓, 35(3) (3), A202 - A202, 日本語
- (一社)日本膵臓学会, 2020年07月, 膵臓, 35(3) (3), A316 - A316, 日本語
- 2020年, 日本消化器病学会雑誌(Web), 117膵癌早期発見に向けての取り組み-当院における膵癌患者の診断前過去CT画像の検討-
- 2020年, 膵臓(Web), 35(3) (3)IPMN併存膵癌とIPMN非併存膵癌の分子病理学的特徴と予後の相違
- 2020年, 膵臓(Web), 35(3) (3)膵切除例を用いた早期慢性膵炎のEUS所見と背景膵の病理所見との対比
- 2020年, 膵臓(Web), 35(3) (3)膵癌の予後におけるTLS(Tertiary lymphoid structure)の意義
- 2020年, 膵臓(Web), 35(3) (3)特異な画像を呈した膵神経内分泌癌の1例
- 内視鏡下採取検体を用いた膵疾患バイオマーカー探索 EUS-FNA(膵液を含む)を用いたメタボローム解析の展望近年の疾患メタボロミクス研究によって、疾患には特有の代謝変容を認めることが明らかになってきた。メタボロミクスは疾患における代謝変容を捉えることによって、バイオマーカーの探索や病態解明に有用となる可能性がある。メタボロミクスを用いたバイオマーカー研究においては、血液など体液を用いた探索が主であったが、近年では膵切除組織や膵嚢胞液を用いた報告も散見されるようになっている。メタボロミクスが分析対象とする代謝物は生体内に広く分布しており疾患特異的なものではなく、安定性にも問題があるため、検体の採取保存や結果の解釈には慎重な検討が必要であるが、EUS関連手技の発展と代謝物分析性能の向上が相まって、EUS-FNA検体を用いたメタボロミクスが微小膵癌の検出や膵疾患の病態解明に大きく寄与することが期待される。(著者抄録)医学図書出版(株), 2020年, 胆と膵, 41(3) (3), 301 - 305, 日本語
- 日本消化器病学会-近畿支部, 2019年10月, 日本消化器病学会近畿支部例会プログラム・抄録集, 111回, 89 - 89, 日本語正中弓状靱帯症候群に脾動脈瘤と膵体部腫瘤を合併した例
- (一社)日本膵臓学会, 2019年06月, 膵臓, 34(3) (3), A166 - A167, 日本語
- (一社)日本膵臓学会, 2019年06月, 膵臓, 34(3) (3), A209 - A210, 日本語
- (一社)日本膵臓学会, 2019年06月, 膵臓, 34(3) (3), A303 - A303, 日本語
- (一社)日本消化器内視鏡学会, 2019年05月, Gastroenterological Endoscopy, 61(Suppl.1) (Suppl.1), 901 - 901, 日本語悪性輸入脚狭窄に対する内視鏡的金属ステント留置術の検討
- (一社)日本消化器内視鏡学会, 2019年05月, Gastroenterological Endoscopy, 61(Suppl.1) (Suppl.1), 923 - 923, 日本語十二指腸乳頭部腫瘍に対する内視鏡的乳頭切除術(EP)後の病理学的評価と予後の検討
- 2019年, Gastroenterological Endoscopy (Web), 61(Supplement1) (Supplement1)悪性輸入脚狭窄に対する内視鏡的金属ステント留置術の検討
- 2019年, 膵臓(Web), 34(3) (3)膵石症に対する内視鏡治療を軸とした治療戦略
- 2019年, Gastroenterological Endoscopy (Web), 61(Supplement1) (Supplement1)十二指腸乳頭部腫瘍に対する内視鏡的乳頭切除術(EP)後の病理学的評価と予後の検討
- 2019年, 日本消化器画像診断研究会プログラム・抄録集, 71st主膵管内に充満した粘液産生に乏しいpancreato-biliary type IPMNの1例
- 2019年, 膵臓(Web), 34(3) (3)死亡の転帰となった薬剤性重症急性膵炎の一例
- 2019年, 膵臓(Web), 34(3) (3)自己免疫性膵炎における造影CT平衡層のCT値によるステロイド治療後の膵萎縮の予測
- 日本消化器病学会-近畿支部, 2019年, 日本消化器病学会近畿支部例会プログラム・抄録集, 110th, 74 - 74, 日本語胆管癌の側方進展度診断における新型経口胆道鏡(SpyGlass DS)の使用経験
- 日本消化器病学会-近畿支部, 2019年, 日本消化器病学会近畿支部例会プログラム・抄録集, 110th, 90 - 90, 日本語術前に癌の確定診断困難であったT1a膵癌の1例
- 日本消化器病学会-近畿支部, 2019年, 日本消化器病学会近畿支部例会プログラム・抄録集, 111th, 78 - 78, 日本語膵管内乳頭粘液性腺癌との鑑別が困難であった自己免疫性膵炎の1例
- (NPO)日本高齢消化器病学会, 2019年, 日本高齢消化器病学会誌, 22(1) (1), 52 - 52, 日本語高齢者におけるERCP後膵炎のリスク解析
- 2019年, Journal of Gastroenterology and Hepatology (Australia), 34(8) (8), 1274速報，短報，研究ノート等（学術雑誌）
- (株)日本臨床社, 2019年, 日本臨床, 77(10) (10), 1734 - 1739, 日本語機能性消化管疾患:上部 IV.特論 上腹部症状を有する患者の膵疾患を見落とさないために
- 科学評論社, 2018年12月, 消化器・肝臓内科 = Gastroenterology & hepatology / 消化器・肝臓内科編集委員会 編, 4(6) (6), 492 - 498, 日本語Peri-pancreatic fluid collection drainageにおける偶発症予防と対処—The management of adverse event for peri-pancreatic fluid collection drainage—特集 Interventional EUSの偶発症予防と対処
- WILEY, 2018年11月, JOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY, 33, 119 - 119, 英語Clinical utility of endoscopic therapy for bile leak associated with posthepatobiliary surgery研究発表ペーパー・要旨（国際会議）
- WILEY, 2018年11月, JOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY, 33, 194 - 194, 英語Significance of pancreatic calcification on preoperative CT image of intraductal papillary mucinous neoplasm研究発表ペーパー・要旨（国際会議）
- WILEY, 2018年11月, JOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY, 33, 537 - 537, 英語The risk and benefit of preoperative pancreatic juice cytology under ERCP in patients with IPMNs研究発表ペーパー・要旨（国際会議）
- 日本膵臓学会, 2018年05月, 膵臓, 33(3) (3), 336 - 336, 日本語
- 日本膵臓学会, 2018年05月, 膵臓, 33(3) (3), 413 - 413, 日本語
- 日本膵臓学会, 2018年05月, 膵臓, 33(3) (3), 580 - 580, 日本語
- (一社)日本消化器内視鏡学会, 2018年04月, Gastroenterological Endoscopy, 60(Suppl.1) (Suppl.1), 842 - 842, 日本語自己免疫性膵炎に合併した胆管病変に対する内視鏡的胆道ドレナージ術の必要性
- (株)アークメディア, 2018年, 肝胆膵, 77(5) (5), 957 - 963, 日本語膵嚢胞診療最前線-IPMN国際診療コンセンサスガイドライン改訂を踏まえて-IPMN国際診療コンセンサスガイドライン最新版(2017年)分枝型IPMN経過観察方法
- Biliary access大辞典 VIII.アクセスルートの確保 EST困難例への対処ESTは、ERCPを用いた診断、治療において必須の手技である。手技の標準化、処置具、機器の進歩により、その有用性や安全性は確立されてきた。しかしながら、乳頭の位置や十二指腸の固定の状態などの解剖学的因子、抗血栓薬内服などの背景因子、術後再建腸管による病態などの因子によって、ESTが困難な症例に遭遇することも少なくない。ESTは膵炎、出血、穿孔などの重篤な合併症と背中合わせであるため、困難症例に対しても安全かつ確実にやり遂げられるよう、胆膵内視鏡医は抗血栓薬に対する正確な知識や、臨機応変に対応できる手技の引き出しをもっておかなければならない。(著者抄録)医学図書出版(株), 2018年, 胆と膵, 39(臨増特大) (臨増特大), 1179 - 1186, 日本語
- 十二指腸乳頭括約筋機能不全(SOD)の疾患概念は、本邦においては広く認知されているとはいえず、適切に診断されていない可能性がある。2016年に改定されたRome基準では、胆道痛と肝酵素の上昇もしくは胆管拡張があり、器質的疾患を認めない症例を、胆道型SODの疑いとすることが推奨され、内視鏡的乳頭括約筋圧測定(SOM)は補助診断に位置づけられた。膵型SODは、ほかに原因が明らかでない反復性急性膵炎のうち、SOMで異常を認めたものとしている。治療に関する十分なエビデンスはないが、一般的には内視鏡的乳頭括約筋切開術(EST)が標準治療として位置づけられている。近年、膵炎発症のリスクが高いという理由から、SOMはあまり行われない傾向にあるが、SOMはSODの診断と治療方針の決定において有用性が最も期待できる客観的検査法であり、今後は検査後膵炎の危険性の少ないSOMの開発、EST有効予測因子の解析が望まれる。(著者抄録)(株)東京医学社, 2017年10月, 消化器内視鏡, 29(10) (10), 1910 - 1915, 日本語記事・総説・解説・論説等（商業誌、新聞、ウェブメディア）
- 【胆膵EUSを極める-私ならこうする(There is always a better way)-】 治療 術後再建腸管症例に対する肝内胆管ドレナージ術(HGS、HJS) 私はこうする現在、術後再建腸管症例における内視鏡的胆道治療は、バルーン内視鏡が第一選択であるが、再建方法や腸管の高度癒着などにより処置が困難な症例も存在する。そのような症例に対して、以前はPTBDが選択されていたが、近年のEUS-BDの普及に伴い、術後再建腸管症例に対する有用性も報告され、今後はPTBDの代替治療になることが予想される。術後再建腸管症例に対するEUS-BDにおける一連の手技の流れは、通常のEUS-BDとほぼ同様であるが、術式や再建法によってアプローチする消化管の種類や形態が変わってくる。そのため、留置するステントの種類を考慮しなければならない。現状では、留置するステントの主流は金属ステントであるが、われわれは術後再建腸管症例においてHGS専用のプラスチックステントを主に使用しており、重篤な偶発症を経験していない。本稿では、当科で行っている術後再建腸管症例に対するEUS-BDの手技の実際やポイントについて概説する。(著者抄録)医学図書出版(株), 2017年10月, 胆と膵, 38(臨増特大) (臨増特大), 1021 - 1028, 日本語記事・総説・解説・論説等（商業誌、新聞、ウェブメディア）
- (有)科学評論社, 2017年09月, 消化器・肝臓内科, 2(3) (3), 282 - 293, 日本語【Interventional EUSの最新情報-適応、手技、デバイス-】Pancreatic fluid collection(膵・膵周囲液体貯留)に対するInterventional EUS記事・総説・解説・論説等（商業誌、新聞、ウェブメディア）
- (一社)日本消化器内視鏡学会, 2017年09月, Gastroenterological Endoscopy, 59(Suppl.2) (Suppl.2), 2182 - 2182, 日本語IPMN由来浸潤癌および併存膵癌におけるEUS背景膵所見の有用性
- WILEY-BLACKWELL, 2016年11月, JOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY, 31, 233 - 233, 英語New method of sphincter of Oddi manometry and therapeutic effect of EST in patients with sphincter of Oddi disorder研究発表ペーパー・要旨（国際会議）
- 超音波内視鏡(EUS)は胆膵診療において重要な役割を担っていることは周知の事実である。また、超音波内視鏡下穿刺吸引法(EUS-FNA)の普及に伴い、診断のみならずその技術を応用した治療も多数報告され、今後さらに発展していくことが予想される。しかしながら、EUSは、術者の技術に依存するところが多く、一定のレベルに達するには時間を要する。EUS手技を習得するにあたり、適応や禁忌はもとよりEUSに使用するスコープや超音波観測装置などの周辺機器の種類や特徴、ならびに検査の手順などの基本的な知識の理解が必要不可欠である。(著者抄録)医学図書出版(株), 2016年11月, 胆と膵, 37(臨増特大) (臨増特大), 1121 - 1129, 日本語
- 膵癌の診断的バイオマーカーにはCA19-9を凌駕するものが未だ存在しないが,近年の分析技術の革新によって,探索の主体はこれまでの蛋白質から,血中循環DNAやnon-coding RNA,エクソソーム,メタボロームなどに拡大し,有力なバイオマーカー候補が次々に報告されるようになった.いずれの生体分子も今後の検証が不可欠ではあるが,画像的な診断技術の向上とも相まって,早期検出や良性疾患との鑑別に有用なバイオマーカーが実用化されることが期待される.(著者抄録)(株)日本メディカルセンター, 2016年11月, 臨床消化器内科, 31(13) (13), 1749 - 1754, 日本語
- (一社)日本消化器内視鏡学会, 2016年04月, Gastroenterological Endoscopy, 58(Suppl.1) (Suppl.1), 715 - 715, 日本語PEP高リスク群へのERCPでは何に留意すべきか 膵炎既往群における手技側因子の解析
- 日本膵臓学会, 2015年05月, 膵臓, 30(3) (3), 412 - 412, 日本語
- 日本膵臓学会, 2015年05月, 膵臓, 30(3) (3), 529 - 529, 日本語
- ＜Point＞メタボロミクスは,有機酸,アミノ酸,脂肪酸,糖などの多種多様な低分子量代謝産物(メタボローム)を対象とした研究である.質量分析(MS)を応用した測定技術が急速な発展を遂げ,メタボロミクスの解析手法として普及したことで,癌の診断バイオマーカー探索研究が広く行われるようになった.大腸癌,膵癌などの消化器癌に対する血清メタボローム解析により,早期診断に有望なバイオマーカー候補が検出された.今後,さらに研究データを蓄積することにより,メタボロミクスによる癌の早期診断が可能になることが期待される.(著者抄録)(株)医学書院, 2015年05月, 臨床検査, 59(5号) (5号), 405 - 410, 日本語[査読有り]記事・総説・解説・論説等（学術雑誌）
- (一社)日本消化器内視鏡学会, 2015年04月, Gastroenterological Endoscopy, 57(Suppl.1) (Suppl.1), 742 - 742, 日本語膵腫瘤性病変の診断における造影ハーモニックEUSの有用性
- (一社)日本消化器内視鏡学会, 2015年04月, Gastroenterological Endoscopy, 57(Suppl.1) (Suppl.1), 762 - 762, 日本語肝門部胆管癌に対する術前胆道ドレナージ中の急性胆管炎の現状と対策
- (一社)日本消化器内視鏡学会, 2015年04月, Gastroenterological Endoscopy, 57(Suppl.1) (Suppl.1), 769 - 769, 日本語選択的胆道挿管困難例に対するUneven Double Lumen Cannulaを用いた新しいアプローチ
- (公社)日本超音波医学会, 2015年04月, 超音波医学, 42(Suppl.) (Suppl.), S433 - S433, 日本語造影超音波は肝腫瘍以外の消化器疾患に必要か? 小膵癌の診断における造影ハーモニックEUSの臨床的有用性
- WILEY-BLACKWELL, 2014年11月, JOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY, 29, 43 - 43, 英語Effectiveness of self-expandable metal stent for afferent loop obstruction caused by cancer recurrence after pancreaticoduodenectomy研究発表ペーパー・要旨（国際会議）
- (一社)日本消化器内視鏡学会, 2014年04月, Gastroenterological Endoscopy, 56(Suppl.1) (Suppl.1), 1192 - 1192, 日本語当院における85歳以上の超高齢者に対する胆膵内視鏡検査の現状[査読有り]
- 膵管カニュレーションは、腹臥位あるいは左側臥位でスコープを直線化し、乳頭正面またはやや見下ろしぎみの視野からカテーテルを垂直に押し当て1〜3時方向を狙い挿管する。2/3の症例では、膵管開口は乳頭部の中央であるが、1/3は胆管と膵管が別々に開口している別開口型やタマネギ型であり、膵管開口は中央より右下に開口しており、注意が必要である。テスト注入で膵管造影が得られれば、腺房造影に注意しつつ、膵管2次分枝までの描出を試み、明瞭な膵管像を撮像する。深部挿管はX線の膵管像を参考に、スコープの引き抜き、左アングル、ダウンアングルによってカテーテルを膵管走行軸に一致させ行う。膵管造影困難例では、開口部の再確認や角度の再調整を行う。先細型カテーテルやガイドワイヤーを併用し、胆管ガイドワイヤー留置法が有効な場合もあるが、膵管非癒合の可能性がある場合は、副乳頭造影も考慮する。(著者抄録)(株)東京医学社, 2014年02月, 消化器内視鏡, 26(2) (2), 280 - 288, 日本語
- WILEY-BLACKWELL, 2013年10月, JOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY, 28, 17 - 17, 英語Evaluation for the indication of prophylactic pancreatic duct stent by propensity score analysis研究発表ペーパー・要旨（国際会議）
- WILEY-BLACKWELL, 2013年10月, JOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY, 28, 17 - 17, 英語In vivo characterization of pancreatic cysts by needle-based confocal laser endomicroscopy研究発表ペーパー・要旨（国際会議）
- 著者らの施設における3cm以内、3個以下の肝細胞癌(HCC)269例に対する経皮的ラジオ波治療の長期治療成績について検討した。その結果、3cm以内、3個以下の累積生存率は3年が76%、5年が59%、7年が44%であった。うち肝障害度Aの累積生存率は3年が86%、5年が71%、7年が61%で、肝障害度Bでは3年が68%、5年が48%、7年が28%であった。また、肝障害度Cでは3年が33%、5年が17%で、3群間において有意差が認められた。一方、2cm以内単発の5年生存率は66%で、うち肝障害度Aでは74%、肝障害度Bでは57%、肝障害度Cでは25%で、3群間で有意差がみられた。更に3cm以内、3個以下の累積無再発5年生存率は肝障害度Aで30%、肝障害度Bで11%で、2群間で有意差が認められた。尚、累積生存率に関与する因子の多変量解析では若年、女性、肝障害度A、PIVKA-II低値、AFP-L3低値、単発において有意差をもって良好な長期予後が得られていた。(NPO)Microwave Surgery研究会, 2011年, Journal of Microwave Surgery, 29, 115 - 118, 日本語[査読有り]
- 日本学術振興会, 科学研究費助成事業 基盤研究(C), 基盤研究(C), 神戸大学, 2019年04月01日 - 2022年03月31日非アルコール性脂肪肝炎への進展に関わる腸管粘膜表層細菌の解析非アルコール性脂肪性肝炎（NASH）は脂肪肝を背景とする肝炎である。さらにBMI正常であるにもかかわらず、膵切除後や消化管術後など腸内細菌変化が起こる患者でNASHを発症する患者が存在する。NASHは、健常人と比べ糞便中の腸内細菌叢構成の違いが指摘されているが、腸管粘膜上皮により近い上皮表面のムチン層内の細菌叢の違いとその病態への影響については不明な点が多い。当研究の目的は患者の腸管粘膜上皮表面の細菌叢に疾患特有性や病勢との関連があるかを明らかにすることである。 これまでの研究で、下部消化管内視鏡による粘膜上皮表面のムチン層に存在する細菌叢の採取方法およびDNA抽出方法、シーケンスライブラリー作成方法などの条件検討を行い、次世代シーケンサーによってNASH患者と非NASH患者2名づつにおける粘膜表層細菌叢の解析を行った。サンプル重量当たりの細菌含有量は糞便中よりも粘膜表層の粘液中の方が多いことを明らかとした。また、NASH患者において、糞便中ではPrevotella属やBacteroides属が減少する一方、Escherichia族が増加する傾向を認めた。さらに、粘膜表層の細菌叢構成においてもPrevotella属の減少およびEscherichia属が増加する傾向が見られた。NASH患者および健常者ともに、同一個人でも粘液中の細菌叢構成は糞便中のものと大きく違う一方で、健常人とNASH患者ともに同一個人内では粘膜表層の細菌は回腸末端や大腸の各場所の部位によらず似通っていることを明らかとした。 現在症例を集積中で、膵疾患患者含め今後さらにサンプルの集積を進め解析を行う。NASH患者と健常者の比較、さらにはNASH患者の中で病勢ごとに腸管粘膜上皮表面の細菌叢を解析することで、NASHの病態に関わりうる粘膜表層の細菌叢を統計学的に明らかにし解析していく。
- 日本学術振興会, 科学研究費助成事業 基盤研究(C), 基盤研究(C), 神戸大学, 2019年04月01日 - 2022年03月31日自己免疫性膵炎の病態形成における腸内細菌の役割自己免疫性膵炎（AIP）は血清IgG4高値とIgG4陽性形質細胞の浸潤を特徴とする機序不明の膵炎で、わが国で報告され現在IgG4関連疾患の一つとして難病指定されている。ステロイドの反応性から自己免疫的機序によるものと推察されているが、特異的治療がなく再燃率も高く問題となっている。申請者のグループはAIPの一部の患者で自己抗体としてラミニン511に対する抗体を同定し、現在病態の解明に取り組んでいる。腸内細菌に対する抗体が膵臓を交差抗原として疾患発症に関与しているのではないかという仮説を立案し研究を行っている。 今年度はAIP患者の血清中免疫グロブりンと反応する腸内細菌のタンパクを同定する目的で、採取した糞便中の腸内細菌を精製しタンパクを抽出したのち、western blotting法によってAIP患者の血清中免疫グロブリンと反応するバンドを確認した。さらに、質量分析装置を用いて、AIP患者の血清中免疫グロブリンと反応するバンド中のタンパクの同定を試みたが細菌由来のタンパクの同定には至らなかった。今後条件検討を繰り返しタンパクの同定を試みる。 また、AIP患者の免疫グロブリンと結合する腸内細菌を分離し、DNA抽出を行った後に次世代シーケンサーによる16Sメタゲノムによる菌叢解析を行った。その結果、AIP患者のIgG4と結合する特異的な細菌の存在が示唆された。今後、AIP患者の症例数を増やし再現性があるかの確認を行う予定である。今後、腸内細菌がどのようにAIPの病態に関わっているか、また腸内細菌が疾患マーカーになりうるかを解析する。