橋本 千樹

Background and study aims : To decrease complications associated with preoperative endoscopic nasobiliary drainage (ENBD) for perihilar cholangiocarcinoma patients, we developed a modified 6-Fr ENBD catheter with multiple side holes (m-ENBD). The aim of this retrospective study was to compare the m-ENBD catheter with a conventional 7-Fr ENBD catheter (c-ENBD). Patients and methods : This study involved 371 patients with suspected perihilar cholangiocarcinoma who underwent ENBD using a c-ENBD catheter or an m-ENBD catheter. The effectiveness of each catheter and the incidence of complications were evaluated. Univariate and multivariate analyses followed by propensity score matching were performed. Results : In 145 patients with total bilirubin levels ≥ 2.0 mg/dL prior to drainage, these levels decreased to < 2.0 mg/dL after ENBD in 81.1 % of the c-ENBD patients and in 74.0 % of the m-ENBD patients ( P  = 0.325). Post-ENBD cholangitis occurred in 24.9 % of the c-ENBD patients and in 12.4 % of the m-ENBD patients ( P  = 0.006). After propensity score matching, the rate of post-ENBD cholangitis ( P  = 0.007) and the number of patients requiring subsequent or additional drainage ( P  = 0.030) were significantly lower in the m-ENBD group. Conclusion : The modified 6-Fr ENBD catheter was associated with a lower incidence of post-ENBD cholangitis than the conventional 7-Fr ENBD catheter, and the incidence of subsequent or additional drainage procedures was also decreased.

本稿では、共焦点レーザー内視鏡を用いた胆管狭窄の診断の現状と課題について述べた。共焦点レーザー内視鏡は感度がよく胆管狭窄の良悪性の診断に有用な検査法と考える。とくに、組織採取が困難な症例では、生検の代用となり得ると思われる。しかし高度炎症性病変と悪性病変との鑑別が困難な場合もあり、今後、病理組織との対比などを行いさらに検証していく必要がある。(著者抄録)

BACKGROUND AND AIM: Chronic pancreatitis (CP) is sometimes diagnosed at the progressed stage. For the early diagnosis of CP, endoscopic ultrasonography (EUS) may be a useful method, but its diagnostic criteria is based on subjective judgment. Shear wave elastography (SW-EG) using transabdominal ultrasonography, which quantifies tissue elasticity as an absolute value, may be an objective and noninvasive method for the diagnosis of CP. METHODS: Eighty-five patients with known or suspected CP who underwent both EUS and SW-EG from October 2012 to July 2016 were included in this study. Patients were categorized into four stages using Rosemont classification and into three stages using Japan Pancreas Society clinical diagnostic criteria 2009 that was EUS-based criteria for the diagnosis of CP. SW-EG was measured five times in the pancreatic parenchyma, and the median value was defined as the pancreatic elastic modulus (PEM). RESULTS: Pancreatic elastic modulus was significantly positively correlated with Rosemont classification stage (rs  = 0.54), Japan Pancreas Society stage (rs  = 0.41), and the number of EUS features (rs  = 0.47). Area under the receiver operating characteristic curve for the accuracy of SW-EG (consistent with CP and suggestive of CP vs normal and indeterminate for CP) was 0.77 (sensitivity 77.1%, specificity 64.9%). In a multivariate linear regression analysis including various EUS features related to PEM, hyperechoic foci with shadowing and lobularity with honeycombing were independent features related to PEM. CONCLUSIONS: Chronic pancreatitis may be diagnosed noninvasively and objectively using SW-EG without performing EUS.

Background and AimThe aim of this study is to elucidate the natural history of pancreatic cystic lesions (PCLs), including branch duct-type intraductal papillary mucinous neoplasm (BD-IPMN), via midterm follow-up analysis of a multicenter prospective observational study (NSPINAL study).MethodsFrom July 2011 to October 2016, 881 patients with PCLs were enrolled in NSPINAL study, and 664 patients with >12months of follow up were analyzed. Every patient was asymptomatic, and endoscopic ultrasound was performed at the initial diagnosis to exclude high-risk individuals. Follow up included endoscopic ultrasound, computed tomography, or magnetic resonance imaging at least once a year. Serial morphological changes and the pancreatic cancer (PC) incidence, including malignant progression of PCLs, were evaluated.ResultsThe 664 patients (358 men) were followed for a median of 33.5months (interquartile range 29). The cyst and main pancreatic duct sizes were 16.69.3 and 2.3 +/- 1.0mm, respectively. Morphologically, 518 cases were multilocular, 137 were unilocular, and 9 had a honeycomb pattern; 269 cases involved multifocal lesions. Ninety-six patients (14.5%) showed worsening progression on imaging. There were two resectable and four unresectable cases of pancreatic ductal adenocarcinoma and three cases of malignant BD-IPMN. The 3-year risk of developing PC was 1.2%. The standardized incidence ratio for PC among PCLs was 10.0 (95% confidence interval 3.5-16.5), and the standardized incidence ratio among BD-IPMN was 16.6 (95% confidence interval 5.1-28.1). Multivariate analysis showed that development of symptoms and worsening progression were significant predictors of PC.ConclusionsMalignant progression of PCLs, including PC development, is not uncommon. Patients with PCLs should be carefully monitored to detect pancreatic ductal adenocarcinoma at early stages.

肝硬変における既存治療抵抗性のそう痒症に対するκ-受容体作動薬ナルフラフィンの治療効果について検討した。2015年4月〜2017年3月に診療した肝硬変671例(男性345例、女性326例、平均年齢68±12歳)を対象とした。抗アレルギー剤が投与されていた86例(12.8%)のうち、ナルフラフィン投与例は49例であった。投与前後のそう痒感をVisual Analogue Scale(VAS)、川島の重症度基準で評価した結果、そう痒感は日中より夜間に強かったが、ナルフラフィン投与によりVAS、川島基準とも有意に改善した。投与前後でVASが30mm以上低下した有効例は18例(有効率72.0%)で、かゆみが消失した症例は9例(36.0%)であり、ナルフラフィン投与の52例中2例に軽度の発疹・嘔気を認めたが、投与中止により速やかに回復した。また、無効群は有効群に比べてASTが有意に高く、ALTが高い傾向にあり、これらの値が治療効果予測因子となる可能性が示唆された。

Background and study aims : Endoscopic ultrasound (EUS) elastography (EUS-E) and contrast-enhanced harmonic EUS (CH-EUS) are useful methods for the diagnosis of pancreatic lesions. This study aims to compare the accuracy of combined EUS-E and CH-EUS with that of EUS-E or CH-EUS alone in the differential diagnosis of pancreatic solid lesions. Patients and methods:  One hundred thirty-six patients with solid pancreatic lesions underwent EUS with both EUS-E and CH-EUS were included. Diagnoses were classified as adenocarcinoma, neuroendocrine tumor (NET), and inflammatory pseudotumor in 95, 22, and 19 patients, respectively. EUS records in each case were rearranged into 3 groups: EUS-E, CH-EUS, and combination. Each modality was randomly reviewed by 3 reviewers with different levels of clinical experience. Sensitivity, specificity, and accuracy of each modality according to each diagnosis group were evaluated. For the combined diagnosis populations, the proportions of correct diagnoses among the 3 modalities were compared by using the multivariate logistic regression analysis. Results : The accuracies of EUS-E, CH-EUS, and the combination of them were 68.4 %, 65.4 %, and 75.7 %, respectively, for adenocarcinoma group; 83.8 %, 82.4 %, and 86.8 % for NET group; 80.1 %, 78.7 %, and 81.6 % for inflammatory pseudotumor group. The multivariate logistic regression analysis for the combined diagnosis populations showed that the proportion of correct diagnoses when EUS-E and CH-EUS were combined was slightly higher than with the other 2 modalities, although the significant differences among them were not observed. Conclusion : EUS-E and CH-EUS combined may improve differential diagnosis of solid pancreatic lesions compared with use of the individual modalities.

OBJECTIVE: To elucidate the mechanism of an increase in the albumin levels by daclatasvir (DCV)/asunaprevir (ASV) therapy, we assessed the factors associated with an increase in the albumin levels. METHODS: We retrospectively analyzed 125 patients with chronic hepatitis C virus (HCV) infection, treated with DCV/ASV from November 2014 to January 2016. RESULTS: Albumin levels significantly increased from 4.0 ± 0.4 g/dL at baseline to 4.2 ± 0.4 g/dL at 24 weeks after the end of treatment (EOT) (P < 0.0001) in 108 patients with SVR. Patients with SVR were divided into three groups according to their baseline albumin levels: group A, ≥ 4 g/dL; group B, 3.6-3.9 g/dL; and group C, ≤ 3.5 g/dL. The increase in albumin levels from baseline to at 24 weeks after EOT was significantly larger in group C (0.5 ± 0.5 g/dL, P < 0.0001) and group B (0.2 ± 0.4 g/dL, P = 0.0059) than in group A (0.0 ± 0.3 g/dL). Multivariate analysis showed that aspartate transaminase (AST) levels was the only factor associated with ≥ 0.3 g/dL increase in albumin levels in groups B and C (P = 0.0305). An increase in albumin levels was significantly correlated with a decrease in AST levels (r = 0.4729, P = 0.0119). CONCLUSION: DCV/ASV therapy resulted in an increase in albumin levels in SVR patients, which was significantly correlated with a decrease in AST levels. It is probable that the reduction of inflammation, but not by reduction of fibrosis, mainly caused an increase in albumin levels.

BACKGROUND: It is difficult to diagnose chronic pancreatitis (CP) objectively because of a lack of standard diagnostic criteria. Endoscopic ultrasonography (EUS) has been used to assess the severity of CP, but the diagnosis of CP using EUS depends on an endosnonographer. The aim of this study was to establish an objective diagnostic method for CP using EUS elastography (EUS-EG). METHODS: A retrospective study was designed and 96 patients underwent EUS-EG for follow-up of known CP, or who were clinically suspected as having CP. CP patients were categorized CP patients as 4 stages using the Rosemont classification (RC). EUS-EG was performed and the "Mean value", which was negatively correlated with pancreatic fibrosis, was calculated using histogram analysis. RESULTS: The "Mean value" of each RC stage (normal, indeterminate for CP, suggestive of CP, and consistent with CP) was 90.1 ± 19.3, 73.2 ± 10.6, 63.7 ± 14.2, and 56.1 ± 13.6, respectively, and showed significant differences for each stage (p < 0.001). There was a significant negative correlation between the "Mean value" and the number of EUS features (r s = -0.59, p < 0.001). Multiple linear regression analysis was used to assess the diagnostic finding of the "Mean value" and showed that hyperechoic foci with shadowing and lobularity with honeycombing maintained their independent diagnostic findings. CONCLUSIONS: EUS-EG was an objective diagnostic apparatus for CP and provided objective information to support EUS features.

AimGenome-wide association studies have revealed that single nucleotide polymorphism (SNP) of human leukocyte antigen (HLA)-DQ is associated with the clearance of hepatitis B surface antigen (HBsAg) in acute hepatitis B virus (HBV) infection. We examined the effects of SNPs on the development of hepatocellular carcinoma (HCC) and markers of HBV in chronic HBV infection.MethodsThe SNPs of HLA-DQ (rs2856718 and rs7453920) were determined in 299 patients with chronic HBV infection.ResultsIn 224 hepatitis B e antigen (HBeAg)-negative patients, those with rs2856718 genotype AG+GG had significantly lower hepatitis B core-related antigen levels (P=0.0184), less frequent treatment with nucleotide/nucleoside analogs (NAs) (P=0.0433), and less frequent HCC development (P=0.0256) than those with genotype AA. Multivariate analysis selected age (P=0.0460), platelet count (P=0.0481), -glutamyl transpeptidase (P=0.0030), and nucleotide/nucleoside analog treatment (P=0.0003) as factors independently associated with HCC development. HBeAg-negative patients with rs7453920 genotype GG had significantly lower HBsAg levels (P<0.0001), a higher prevalence of HBV genotype C (P=0.0063), and a lower prevalence of the wild-type basal core promoter region (P=0.0045) than those with genotype AA + AG. Multivariate analysis selected age (P<0.0001), platelet count (P=0.0021), HBV DNA levels (P=0.0314), wild type of precore region (P=0.0015), and rs7453920 (P<0.0001) as factors independently associated with HBsAg levels.ConclusionThis study revealed an association between rs2856718 and HCC development and an association between rs7453920 and HBsAg levels.