橋本 千樹

【背景と目的】一般的に切除不能悪性遠位胆道狭窄のドレナージには内径が太いself-expandable metal stent(SEMS)の方が閉塞再発までの時間(time to recurrence obstruction;TRBO)が長いと考えられているが、fully covered SEMS(FCSEMS)において内径別のTRBOについての検討はない。この多施設前向き研究の目的は、切除不能遠位胆管悪性狭窄患者における8mm径と10mm径のFCSEMSのTRBOと胆嚢炎や膵炎などの偶発症の頻度を比較検討することである。【方法】この多施設前向き研究には18施設が参加した。エントリーされた患者は8mm径群と10mm径群に割付けされた。この両群においてTRBO、8mm径FCSEMSの10mm径に対する非劣性の有無の検討、全生存期間、偶発症の頻度とその種類、死亡時ステント開存率を比較検討した。【結果】TRBOの中央値は8mm径群(n=102)と10mm径群(n=100)で有意差を認めなかった(275日と293日、P=0.971)。8mm径群の10mm径群に対するハザード比は0.90であった(80%信頼区間は0.77-1.04であり上限が帰無仮説の許容ハザード比1.33より小さかった)。この結果によってTRBOにおいて8mm径ステントは10mm径ステントに対して統計的に非劣勢であると判断された。全生存期間、偶発症の発症率、死亡時ステント開存率に有意差は認めなかった。【結論】8mm径FCSEMSは10mm径FCSEMSにTRBOにおいて非劣性であった。この結果は今後のSEMS新規開発に重要である。(著者抄録)

BACKGROUND AND AIM: Needle-based confocal laser endomicroscopy (nCLE) allows for real-time optical biopsies during endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA). Little is known about nCLE imaging of gastrointestinal subepithelial lesions (GI-SEL); therefore, we determined its feasibility. METHODS: We carried out EUS, nCLE, and finally FNA in 25 patients with GI-SEL between November 2015 and December 2018. We retrospectively compared nCLE findings with pathological findings of EUS-FNA or surgical specimens. For concordance analysis, two endoscopists independently validated representative nCLE images 5 months or more after examinations. RESULTS: Adequate sample acquisition rate of EUS-FNA was 67% per needle pass and 96% per patient. EUS-FNA was diagnostic in 80% (20/25), suspicious in 4% (1/25), and nondiagnostic in 16% (4/25). nCLE image acquisition rate was 100% and its concordance rate with final pathology was 88% (22/25), which was not significantly different from diagnostic and suspicious EUS-FNA. nCLE could differentiate GI stromal tumors (GISTs) from leiomyoma, in that GISTs were characterized by contrast-enhanced densely populated spindle cell tumors with unenhanced rod-shaped nuclei in 93% of 14 patients, whereas leiomyomas were characterized by narrower spindle cell tumors with fewer and smaller unenhanced nuclei in 100% of three patients. In rectal metastasis from lung adenocarcinoma, some pleomorphic dark nests were observed. At concordance analysis between the two endoscopists' validation results, κ value was 0.560 (P < 0.001), indicating moderate agreement. There were no adverse events associated with nCLE and EUS-FNA. CONCLUSION: Needle-based confocal laser endomicroscopy can be safe and useful for on-site detection of abnormalities of GI-SEL (UMIN 000013857).

10mm以下の膵癌は予後が比較的良好で、いかに早期に発見するかが膵癌の予後の改善のために重要である。近年、超音波技術の進歩は目覚ましく、膵癌早期診断におけるUS、EUSの果たす役割は近年大きくなりつつある。とくに造影超音波は、腫瘍の血行動態を詳細に評価することが可能で質的診断に有用である。また周囲の膵実質とのコントラストが強くなるため存在診断にも有用である。本稿では、膵癌、とくに10mm以下の小膵癌の診断におけるUS、EUSの役割について造影超音波を中心に概説する。(著者抄録)

OBJECTIVE: The present study aimed to elucidate the effect of switching from branched-chain amino acid granules to branched-chain amino acid-enriched nutrient in patients with cirrhosis with hypoalbuminemia. METHODS: Twenty-six patients with cirrhosis with hypoalbuminemia despite treatment with branched-chain amino acid granules containing 12 g of branched-chain amino acid were enrolled in the prospective study. The branched-chain amino acid-enriched nutrient and control groups were composed of 16 and 10 patients, respectively. The patients in branched-chain amino acid-enriched nutrient group switched to branched-chain amino acid-enriched nutrient mixture containing 12.2 g of branched-chain amino acid and 410 kcal with a half of it consumed as a late evening snack, and the patients in the control group continued branched-chain amino acid granules. Laboratory data related to nutrition parameter were assessed at baseline, 3 months after baseline, and at 6 months after baseline. RESULTS: Two patients were withdrawn; hence, nine and 15 patients in the branched-chain amino acid granules and branched-chain amino acid-enriched nutrient groups, respectively, were subjected to full analysis. Serum albumin levels and total lymphocyte counts in both groups did not change in the study period. The branched-chain amino acid-to-tyrosine ratio in the branched-chain amino acid-enriched nutrient group significantly increased from baseline to 6 months after baseline (P = 0.030), whereas that in the control group did not increase. CONCLUSION: Switching from branched-chain amino acid granules to branched-chain amino acid-enriched nutrients improves branched-chain amino acid-to-tyrosine ratio in patients with cirrhosis with hypoalbuminemia.

EUS-FNAに伴うneedle tract seedingは理論的には常にあり得るのだと考える姿勢が重要である。膵の嚢胞性疾患や充実性腫瘍に対して行われたEUS-FNAが原因と思われるneedle tract seedingやdisseminationは英文文献だけでも何例も報告されている。一方で、多数例の報告による統計学的な検討ではEUS-FNAによるneedle tract seedingは"結果"に大きな影響を与えなかったという結論で一致している。Needle tract seedingやdisseminationの問題は、多数例の検討では統計学的に無視し得るという理由で、実際の臨床現場でも無視してよい、と簡単には割り切れない種類のものだ。EUS-FNAを行うことによって、たとえneedle tract seedingが生じたとしても、それよりもさらに重要な生命予後に寄与する情報が得られることを切に期待する。(著者抄録)

PURPOSE: Pancreatic fibrosis or fibrosing reactions have been reported in intraductal papillary-mucinous neoplasm (IPMN) patients. We assessed whether a higher elastic modulus (EM) measured using shear wave elastography (SW-EG) correlated with the existence of branch-duct (BD) IPMN. METHODS: In total, 183 normal pancreas (NP) and 123 BD-IPMN cases were enrolled. First, we assessed the difference in pancreatic EM (PEM) at different sites (head or tail side of the cyst). Second, a comparison was done between the median PEM of the NP and the BD-IPMN cases. Receiver-operating characteristic analysis was performed to determine the BD-IPMN diagnostic capabilities. Finally, in patients whose cyst was not visualized, the test-positive rate was determined. RESULTS: No significant difference was seen between the cyst head side PEM (4.61 kPa) and the tail side PEM (5.35 kPa) (P = 0.471). Among these cases matched by age, 73 were selected each from NP and BD-IPMN cases (median age 65 years). The median PEM of the BD-IPMN cases (5.18 kPa) was significantly higher than that of the NP cases (3.17 kPa) (P < 0.001). When the cut-off value was set at 4.75 kPa, the sensitivity, specificity, PPV, NPV, and accuracy were 75.3%, 64.4%, 72.3%, 67.9%, and 69.9%, respectively. The cut-off value of 4.75 kPa helped for the indirect selection of BD-IPMN patients (10/17, 58.8%) whose cyst was not detected on B-mode ultrasonography. CONCLUSION: SW-EG measurement of the underlying pancreatic parenchyma may correlate with the presence of BD-IPMN.

Evaluation of the pancreatic elastic modulus (PEM) using shear wave elastography (SWE) requires at least 5 measurements to ensure reproducibility. The aim of this study was to evaluate improvement in reproducibility of SWE, using the propagation display method in normal pancreas ([NP] phase 1) and to examine the differences in PEM between NP and chronic pancreatitis (CP), intraductal papillary mucinous neoplasm (IPMN) and autoimmune pancreatitis ([AIP] phase 2). In phase 1, the measurement success rate, median PEM in repeated measurements and appropriate number of SWE measurements were determined in 109 cases with NP. In phase 2, PEM was measured in CP (n = 10), IPMN (n = 31) and AIP (n = 5), using the required number of SWE measurements determined in phase 1. In phase 1, the measurement success rate was 93.9% (92/109 cases). The median PEM for NP was 14.6 kPa and the appropriate number of SWE measurements was at least 3. In phase 2, the median PEMs in CP, IPMN and AIP were 19.6, 18.1 and 17.2 kPa, respectively, with significant differences between NP and CP (p = 0.0133) and between NP and IPMN (p = 0.0436). Use of the propagation display method in SWE improves the reproducibility of measurement of PEM.

OBJECTIVES: The time to recurrent biliary obstruction (TRBO) of unresectable distal malignant biliary obstruction is generally thought to be longer when a self-expandable metal stent (SEMS) with a thicker inner diameter is used for drainage, but the dependence on the inner diameter using a fully covered SEMS (FCSEMS) is uncertain. The objective of this multicenter prospective study was to compare TRBO and adverse events, such as cholecystitis and pancreatitis, in treatment of patients with unresectable malignant biliary obstruction using 8- and 10-mm diameter FCSEMS. METHODS: Eighteen tertiary-care centers participated in the study. Patients were allocated to the 8- and 10-mm diameter groups. TRBO, non-inferiority of the 8-mm FCSEMS, overall survival time, frequency and type of adverse events, and non-recurrent biliary obstruction (RBO) rate at the time of death were compared between the two groups. RESULTS: Median TRBO did not differ significantly between the 8-mm (n = 102) and 10-mm (n = 100) groups (275 vs 293 days, P = 0.971). The hazard ratio of the 8- to 10-mm groups was 0.90 (80% confidence interval, 0.77-1.04; upper limit lower than the acceptable hazard ratio [1.33] of the null hypothesis). Based on these findings, the 8-mm diameter stent was determined to be non-inferior to the 10-mm diameter stent. Survival time, incidence of adverse events and non-RBO rate at the time of death did not differ significantly between the two groups. CONCLUSIONS: Time to RBO with an 8-mm diameter FCSEMS was non-inferior to that with a 10-mm diameter FCSEMS. This finding is important for development of future SEMS.

OBJECTIVE: The aim was to assess the relationship between muscle mass depletion and chronic hepatitis C virus (HCV) infection. PATIENTS AND METHODS: We retrospectively evaluated abdominal computed tomography data for 611 patients. The participants included 302 patients with HCV infection and 309 patients with gallstones (as a control). The skeletal muscle mass at the level of the third lumber vertebra (L3) was measured from the computed tomography images and normalized for height to calculate the L3 skeletal muscle index (L3-SMI, cm/m). Statistical analysis was carried out separately for each sex, given that L3-SMI differs significantly between men and women. RESULTS: L3-SMI showed no significant difference between chronic hepatitis patients and gallstone patients in either sex. L3-SMI was significantly lower in male cirrhotic patients than in those with chronic hepatitis (P<0.001). The Child-Pugh score was correlated negatively with L3-SMI in male patients with HCV-related cirrhosis (ρ=0.200, P=0.031). In addition, the BMI in both sexes was associated with L3-SMI in the gallstone and chronic hepatitis group, in the chronic hepatitis and liver cirrhosis group, and in the liver cirrhosis group. CONCLUSION: Skeletal muscle mass is not affected by chronic HCV infection in patients without cirrhosis and decreases in accordance with liver disease progression in male patients with chronic HCV infection.

PURPOSE: Abdominal ultrasound (US) can visualize the esophagogastric junction (EGJ) as a hyperechoic area in the dorsal portion of the lateral segment of the liver. We prospectively evaluated the EGJ using US elastography (US-EG) in patients with reflux esophagitis (RE) to examine prediction of distal esophageal function. METHODS: Of 108 patients undergoing US-EG and esophagogastroduodenoscopy, 102 in whom the EGJ was observed for ≥ 15 s were included. The subjects were divided into a RE group (n = 41, Grade M/A/B:24/13/4 according to modified Los Angeles Classification) and a non-RE group (n = 61). Direct strain elastography (LOGIQ E9, GE Healthcare), which gives a semi-quantitative elasticity index within a region of interest including the lateral segment, was used as a standard for measurement of the change in stiffness (CS) at the EGJ. RESULTS: The number of CS as determined by US-EG was 6.0 (5.5-6.7) in the RE group and 8.6 (6.6-10.0) in the non-RE group (P < 0.0001). In ROC analysis, the AUC was 0.8415 for diagnosis of RE using the number of CS. At a cut-off of 7.7, the sensitivity, specificity, and accuracy for diagnosis were 92.7, 65.6, and 74.5%, respectively. CONCLUSION: The presence of RE can be predicted based on US-EG.

OBJECTIVE: To evaluate the efficacy and safety of alternate-day administration of S-1 as second-line chemotherapy for unresectable pancreatic cancer in a multicenter, randomized, phase II study. METHODS: Patients with histologically proven, unresectable pancreatic cancer treated with chemotherapy not including S-1 as first-line therapy were randomly assigned to receive either daily or alternate-day treatment with S-1. The primary end point was overall survival (OS), and the secondary end points were progression-free survival (PFS), time to treatment failure (TTF), response rate, and adverse events. RESULTS: A total of 77 patients were enrolled, of which 75 were included in the final analysis. The median OS was 4.5 months in the daily group and 4.4 months in the alternate-day group (HR 1.178; 95% CI 0.741-1.875), with no significance in PFS and TTF. The response rate was 2.8% in the daily group and 0% in the alternate-day group. Grade 3 or higher adverse events occurred with significantly higher incidence in the daily group (47.2 vs. 25.6%, p = 0.044). CONCLUSION: As a second-line chemotherapy for unresectable pancreatic cancer, although the efficacy in both groups was comparable and we can expect fewer toxicities with alternate-day administration of S-1, the noninferiority of alternate-day treatment to daily treatment with S-1 was not verified.

Background and Aims: Several studies have shown the benefits of endoscopic ultrasound-guided fine needle biopsy (EUS-FNB) using a Franseen needle for histological assessment. However, studies focusing on pancreatic diseases are limited and the safety of this method has not been well assessed. We aimed to assess the current status and issues of EUS-FNB in the diagnosis of pancreatic diseases. Materials and Methods: We retrospectively reviewed 87 consecutive EUS-FNB specimens using either a 22-gauge Franseen needle (Group A, N = 51) or a conventional 22-gauge fine-needle aspiration needle (Group B, N = 36) for pancreatic diseases, and the diagnostic accuracy and safety were compared. Final diagnoses were obtained based on surgical pathology or a minimum six-month clinical follow-up. Results: Although the diagnostic accuracy for malignancy was 96.1% in Group A versus 88.9% in Group B, with no statistically significant difference (P = 0.19), the median sample area was significantly larger in Group A (4.07 versus 1.31mm2, P < 0.0001). There were no differences between the two needles in the locations from which the specimens were obtained. Adverse events occurred in one case (2%) in Group A (mild pancreatitis) and none in Group B with no statistical significance (P = 0.586). Although there was no case of bleeding defined as adverse events, 2 cases in Group A showed active bleeding during the procedure with increase in the echo-free space, which required CT scanning to rule out extravasation. Eventually, the bleeding stopped spontaneously. Conclusions: Given its guaranteed ability to obtain core specimens and comparable safety, and although the risk of bleeding should be kept in mind, EUS-FNB using a Franseen needle is likely to become a standard procedure for obtaining pancreatic tissue in the near future.

Background and study aims  Biliary metallic stents are used to drain unresectable malignant distal biliary obstructions. This study aimed to evaluate the efficacy of a novel 12-mm-diameter covered, self-expandable end bare metal stent (12-mm CSEEMS). Patients and methods  We evaluated 99 patients with unresectable malignant distal biliary obstructions treated with covered biliary metallic stents. Of the 99 patients, 33 underwent 12-mm CSEEMS placement between June 2015 and April 2017 (12-mm-CSEEMS group) and 66 underwent 10-mm fully-covered self-expandable metal stent (FCSEMS) placement between January 2010 and July 2015 (10-mm-FCSEMS group). The overall survival (OS), the recurrent biliary obstruction (RBO), cause of RBO, time to RBO (TRBO) and adverse events in 12-mm-CSEEMS group and 10-mm-FCSEMS group were evaluated retrospectively. Results  The OS tended to be longer in the 12-mm-CSEEMS group (log rank, P  = 0.081) and TRBO was significantly longer in the 12-mm-CSEEMS group (log rank, P  = 0.001) than in the 10-mm-FCSEMS group. Both univariate (HR, 0.449; 95 % CI, 0.27967 - 0.72215; P  = 0.001) and multivariate (HR, 0.458; 95 % CI, 0.28395 - 0.73744; P  = 0.001) Cox hazard analysis found that risk of RBO was significantly lower in 12-mm CSEEMS than in 10-mm FCSEMS. There were no significant differences between the 12-mm-CSEEMS group and 10-mm-FCSEMS group regarding the cause of RBO and adverse events. Conclusions  The 12-mm CSEEMS showed a low risk of RBO compared with 10-mm FCSEMS and was considered to be effective and safe for draining unresectable malignant distal biliary obstruction.