Introduction: Ustekinumab is an IgG1 kappa monoclonal antibody directed against the common p40 subunit of interleukin-12 and interleukin-23, which activate Th1- and Th17-mediated immune responses, respectively. It has proven efficacy for the treatment of moderate to severe ulcerative colitis (UC) in the UNIFI Phase III clinical trial; however, data on its efficacy in the real world is limited. In this study, we aimed to assess the real-world efficacy of ustekinumab.Methods: This observational study included 30 patients with UC who received ustekinumab from April 2020 to April 2022. We examined demographic information, disease type and activity (Mayo score, partial Mayo score [PMS]), use of biologics, concomitant use of predonisolone (PSL), 8-week ustekinumab clinical response rate, remission induction rate, 44- and 152-week remission maintenance rate, continuation rate, and 44-week steroid-free remission rate. The primary outcomes were the short- and long-term efficacy of ustekinumab.Results: Included patients (53% women; mean age: 41.2 years [16–80 years]) had an average disease duration of 86 weeks. Mayo’s score (median) was 7.4 and the PMS was 5.4. Two (7%), 24 (80%), and four (13%) patients had a Mayo endoscopic sub-score (MES) of MES1, MES2, and MES3, respectively. The median serum CRP was 1.0 mg/dL. Five patients had no history of biotherapy (naive), while 8 and 17 had a history of one and two or more biologic agents, respectively. Eight patients were PSL-resistant and 22 were PSL-dependent. The 8-week clinical response rate was 73%, and the clinical remission induction rate was 70%. The remission maintenance rates at 44 and 152 weeks were 67% and 63%, respectively. The ustekinumab retention rate was 67% (86-week mean follow-up period). Regarding biologic failure cases, the clinical response rate in the failure group with up to one biologic agent (including naive cases) was 84.6%, which was higher than the 58.0% rate in the failure group with two or more biologic agents (p=0.06). Steroid-free remission rates at 44 and 152 weeks were 63% each. In the logistic regression analysis parameters for discontinuation of ustekinumab, only PMS remained significant after multivariate analysis (p=0.018).Conclusion: Our study showed short-term and long-term ustekinumab effectiveness, especially with comparative low disease activity.

遠位悪性胆管狭窄に対する経乳頭的胆道ドレナージにおいて自己拡張型メタリックステント(self-expandable metallic stent:SEMS)の中でもポリウレタンやPTFEなどの膜で被覆されたcovered SEMS(CSEMS)は腫瘍増殖を防ぐことができるとされる一方でさまざまな要因によりCSEMSは逸脱・迷入を起こし,閉塞性黄疸,閉塞性胆管炎の再燃を引き起こす。CSEMS迷入に対する最大のトラブルシューティングは「迷入させないこと」であり,事前議論,胆管造影,適切なデバイス選択がまず行われなくてはならない。迷入に対しては「乳頭拡張をしておく」,「カバーの腐食・ingrowthの可能性を確認する」,「迷入したCSEMSのカバーが外巻きか内巻きかを確認しておく」,「迷入したCSEMSと胆管狭窄部との位置関係を確認する」といったtipsを理解し,引き抜き法か翻転抜去法を選択する対応が求められる。ただしまずはドレナージ不良に対する治療を最優先すべきであり,無理な迷入SEMSの抜去は決して行ってはならない。(著者抄録)

OBJECTIVES: No comprehensive study has examined short- and long-term adverse outcomes of endoscopic ultrasound (EUS)-guided treatment of pancreatic fluid collections (PFCs) including walled-off necrosis (WON) and pseudocysts. METHODS: In a multi-institutional cohort of 357 patients receiving EUS-guided treatment of PFCs (228 with WON and 129 with pseudocysts), we examined PFC type-specific risk factors for procedure-related adverse events (AEs), clinical failure, and recurrence. Odds ratios (ORs) and hazard ratios (HRs) with 95% confidence intervals (CIs) were computed using the logistic and Cox regression models, respectively, adjusting for potential confounders. RESULTS: AEs were observed predominantly in WON, and risk factors were WON extension to the pelvis (OR, 2.49; 95% CI, 1.00-6.19) and endoscopic necrosectomy (OR, 5.15; 95% CI, 1.61-16.5). Risk factors for clinical failure in WON treatment included higher Charlson Comorbidity Index (OR for ≥3 vs. ≤2, 2.58; 95% CI, 1.05-6.35), extension to the pelvis (OR, 3.63; 95% CI, 1.57-8.43), non-use of a lumen-apposing metal stent (OR, 2.88; 95% CI, 1.10-7.54), and percutaneous drainage (OR, 3.73; 95% CI, 1.27-10.9). Patients with pseudocysts extending to the paracolic gutter and need for more than two endoscopic / percutaneous procedures had ORs for clinical failure of 5.28 (95% CI, 1.10-25.3) and 5.52 (95% CI, 1.61-18.9), respectively. Pseudocysts requiring the multigateway approach were associated with high risk of recurrence (HR, 4.00; 95% CI, 1.11-11.6). CONCLUSIONS: The adverse outcomes at various phases of EUS-guided PFC treatment may be predictable based on clinical parameters. Further research is warranted to optimize treatment strategies for high-risk patients (registration number, UMIN000044130).

Abstract Background and Aim A multicenter, open‐label randomized Phase II trial was conducted to determine whether low‐dose gemcitabine plus nab‐paclitaxel (GnP) could improve tolerability and show equivalent efficacy to the standard‐dose GnP for elderly patients with metastatic pancreatic cancer. Methods Consecutive patients aged ≥65 years with metastatic pancreatic cancer who presented at one of four Japanese referral centers between November 2016 and January 2021 were enrolled. The 60 patients were randomly assigned to low‐ or standard‐dose groups with a 1:1 ratio. Patients in the low‐dose GnP group received gemcitabine at a dose of 250 mg/m² and nab‐paclitaxel at 125 mg/m². Results Low‐dose GnP significantly decreased the rate of cases requiring dose reduction (16.7% vs 63.3%). The response rate (36.7% vs 33.3%) and progression‐free survival (7.3 vs 8 months) were comparable between the low‐ and standard‐dose groups as determined by independent review. The difference in the median overall survival between the two groups was not significant (7.9 vs 12 months). The proportion of patients with hematologic and non‐hematologic treatment‐related adverse events was comparable between the two groups. Conclusion Low‐dose GnP had an equivalent efficacy to conventional therapy; however, it did not reduce adverse events.

BACKGROUND: This prospective cohort study evaluated the feasibility of using endoscopic ultrasound-guided fine-needle biopsy (EUS-FNB) samples for comprehensive mutational analysis of cancer-related genes using microtissues. METHODS: Fifty patients with suspected pancreatic cancer presenting consecutively at the Kindai University Hospital between January 2018 and January 2019 were enrolled. Cancerous tissues from EUS-FNB were obtained from each tumor and subjected to histological examination and mutational analysis. The primary endpoint was the collection rate of EUS-FNB specimens suitable for comprehensive cancer panels using deep sequencing. Clinical history and genetic variations between the disease control and progressive disease groups of patients on chemotherapy were evaluated as secondary endpoints. RESULTS: The collection rate of EUS-FNB specimens suitable for comprehensive cancer panels using deep sequencing was 93.6%. The cancer panel was sequenced for 25 patients with pancreatic cancer treated initially with systemic chemotherapy. Mutation in p53 and Smad4 were positively and negatively associated, respectively, with disease control at the initial evaluation. The median time to progression in 15 patients with p53 and without Smad4 mutations was 182.0 days; whereas, it was 92.5 days in other 10 patients; this difference was significant (p = 0.020). CONCLUSIONS: Tissue samples from EUS-FNB were suitable for mutational analysis. Pancreatic cancers with p53 and without Smad4 mutations responded better to chemotherapy and had a better prognosis than those others.

Abstract Background and Aim Serum leucine‐rich alpha‐2 glycoprotein level has been reported to be a useful biomarker in assessing mucosal healing in patients undergoing biotherapy, where mucosal lesions caused by ulcerative colitis are difficult to assess endoscopically. However, no such reports have been reported in biotherapy‐naïve cases. Methods Sixty‐eight patients with ulcerative colitis (UC) who were biotherapy‐naïve at Kindai University Hospital between October 2021 and October 2022 were enrolled. We prospectively examined the correlation between leucine‐rich alpha‐2 glycoprotein (LRG), C‐reactive protein (CRP), erythrocyte sedimentation rate (ESR), and Geboes scores with clinical endoscopic activity using the Mayo endoscopic subscore (MES). Results Mucosal healing was achieved in 39 (57%) patients. Univariate analysis revealed that the factors associated with mucosal healing were LRG (P = 0.0024), CRP (P = 0.1078), ESR (P = 0.0372), and Geboes scores (P = 0.0075). Logistic regression analysis identified LRG and Geboes scores as independent factors associated with mucosal healing assessed using MES (P = 0.0431 for LRG and P = 0.0166 for Geboes scores). Conclusion LRG was found to be the easiest marker to monitor disease activity and mucosal inflammation in UC patients with biotherapy‐naïve cases, with a performance equivalent to that of Geboes scores.

＜文献概要＞南大阪地域(面積880km2,25の市町村,人口230万人)における各施設の急性膵炎に対する診療体制の現状の把握,施設間連携の問題点の抽出,連携の強化により,急性膵炎治療の地域連携モデル構築を試みた.南大阪地域101施設へ,年間診療膵炎患者数,各施設での対応可能な膵炎の診療内容,Pancreatitis Bundlesの使用率,受け入れの実際,高次施設への搬送における問題点などについてアンケート調査を行い,「急性膵炎地域連携構築会議」と称して各病院の医師(外科/救命科/内科),医療連携事務が参加する会合を年に一度開催し,地域の現状を把握するとともに搬送に有用な膵炎MAPを作成し,膵炎治療成績向上を図った.Pancreatitis Bundlesの使用率は2016年の29%から2022年は86%にまで上昇した.また,南大阪地域における急性膵炎死亡率も2019年の全体で1.5%,重症膵炎に限定すると16.2%から,2021年は全体で1.1%,重症膵炎7.9%と改善が認められた.南大阪膵炎MAPと,地域連携構築会議を毎年開催することで,南大阪地区において急性膵炎患者の地域連携が構築されつつあり,急性膵炎患者に対する治療成績の向上と予後の改善が期待される.

This study aimed to examine occupational radiation exposure to the lens of the eyes during endoscopic retrograde cholangiopancreatography (ERCP). In this multicenter, prospective, observational cohort study, we collected data regarding occupational radiation exposure to the lens of the eyes during ERCP. We measured radiation exposure of patients and examined its correlation with occupational exposure. In dosimetrically-measured ERCPs (n = 631), the median air kerma at the patient entrance reference point, air kerma-area product, and fluoroscopy time were 49.6 mGy, 13.5 Gycm2, and 10.9 min, respectively. The median estimated annual radiation dose to the lens of the eyes was 3.7, 2.2, and 2.4 mSv for operators, assistants, and nurses, respectively. Glass badge over lead aprons and eye dosimeter results were similar in operators but differed in assistants and nurses. A strong correlation was shown between eye dosimeter measurements and patients' radiation exposure. The shielding rates of the lead glasses were 44.6%, 66.3%, and 51.7% for operators, assistants, and nurses, respectively. This study revealed the actual occupational exposure dose for the lens of the eyes during ERCP and the efficacy of lead glass. Values of radiation exposure to patients can help estimate exposure to the lens of the eyes of medical staff.

BACKGROUND: Treatments for patients with gastric outlet obstruction (GOO) due to unresectable pancreatic cancers (URPC) include gastrojejunostomy (GJJ) and endoscopic duodenal stent placement (EDSP). This study compared the efficacy and safety of GJJ and EDSP in patients with GOO due to URPC. METHODS: This study retrospectively evaluated consecutive patients with GOO due to URPC who underwent GJJ or EDSP between April 2016 and March 2020. The efficacy and safety of GJJ and EDSP were compared with propensity score analysis. Subgroup analyses of overall survival (OS) were compared after propensity matching. RESULTS: Data were obtained from 54 patients who underwent GJJ and from 73 who underwent EDSP at five tertiary care hospitals. After propensity matching, OS was significantly longer in patients who underwent GJJ than EDSP (110 vs. 63 days, respectively; p = 0.019). Evaluation of long-term adverse events showed that the frequency of cholangitis and obstructive jaundice was significantly lower in the matched GJJ than in the matched EDSP group (p = 0.012). Subgroup analyses showed that OS in patients with good performance status (PS; p = 0.041), biliary obstruction (p = 0.007), and duodenal obstruction near the papilla (p = 0.027), and those receiving chemotherapy (p = 0.010), was significantly longer in the matched GJJ group than in matched EDSP group. CONCLUSION: GJJ provides longer OS than EDSP for patients with GOO caused by URPC, especially for patients with good PS, biliary obstruction, and duodenal obstruction near the papilla, and those receiving chemotherapy.

【背景と目的】この前向き多施設共同研究は,膵癌とその他の膵腫瘍の鑑別におけるティッシュハーモニック(Tissue harmonic endoscopic ultrasonography;TH-EUS)と造影ハーモニックEUS(Contrast-enhanced harmonic endoscopic ultrasonography;CH-EUS)の正診率を比較検討することを目的とした.【方法】2013年8月から2014年12月の間にかけて,固形膵腫瘍の連続症例を前向きに登録した.TH-EUSとCH-EUSの正診率を評価するため,TH-EUSの4所見(境界不明瞭,辺縁不整,内部低エコー,内部エコー不均一)とCH-EUSの4所見(早期相および後期相のそれぞれでhypoenhancement,heterogeneous enhancement)を比較し,各手法のどの所見が最も膵癌の診断に適しているか検討した.また,TH-EUSとCH-EUSにおける膵癌の診断についての観察者間一致度も評価した.【結果】204名の患者が本研究に登録された.膵癌の診断において,エキスパートと非エキスパートによる観察者間一致度は,TH-EUSではそれぞれ0.33-0.50と0.35-0.50,CH-EUSではそれぞれ0.72-0.74と0.20-0.54であった.TH-EUSの所見のうち膵癌の鑑別において最も正診率の高い所見は辺縁不整であり,感度,特異度,正診率はそれぞれ95.0%,42.9%,78.9%であった.CH-EUS所見のうち膵癌の正診率の高い所見は後期相hypoenhancementであり,感度,特異度,正診率はそれぞれ90.8%,74.6%,85.8%であった.CH-EUS(後期相hypoenhancement)の膵癌の正診率は,TH-EUS(辺縁不整)よりも有意に高かった(p<0.001).【結語】CH-EUSはTH-EUSと比較して,膵癌診断能および診断における再現性を向上させた.UMIN(000011124).(著者抄録)

Background/Aims: Bispectral index (BIS) monitors process and display electroencephalographic data and are used to assess the depth of anesthesia. This study retrospectively evaluated the usefulness of BIS monitoring during endoscopic ultrasonography (EUS). Methods: This study included 725 consecutive patients who underwent EUS under sedation with propofol. BIS monitoring was used in 364 patients and was not used in 361. The following parameters were evaluated: (1) median dose of propofol; (2) respiratory and circulatory depression; (3) occurrence of body movements; (4) awakening score >8 at the time; and (5) awakening score 2 hours after leaving the endoscopy room. Results: The BIS group received a significantly lower median dose of propofol than the non-BIS group (159.2 mg vs. 167.5 mg; p=0.015) in all age groups. For patients aged ≥75 years, the reduction in heart rate was significantly lower in the BIS group than in the non-BIS group (1.2% vs. 9.1%; p=0.023). Moreover, the occurrence of body movements was markedly lower in the BIS group than in the non-BIS group (8.5% vs. 39.4%; p<0.001). Conclusions: During EUS examination, BIS monitoring is useful for maintaining a constant depth of anesthesia, especially in patients 75 years of age or older.

Background: The value of contrast-enhanced harmonic EUS (CH-EUS) for diagnosis of portal vein invasion in patients with pancreatic cancer was evaluated. Patients and Methods: This single-center, retrospective study included consecutive patients with pancreatic cancer who underwent both surgical resection after preoperative EUS, CH-EUS, and contrast-enhanced computed tomography (CE-CT) examinations between April 2015 and August 2017. CH-EUS evaluation was performed during the late phase. Portal vein invasion on EUS and CH-EUS was defined as no continuity in the line of the vessel wall. Definition of portal vein invasion on CE-CT was based on the Loyer's criteria. The accuracy of three modalities for diagnosis of invasion into the portal vein was compared using the McNemar's test. Results: Eighty-eight patients (mean age: 71.0 years, ratio of male to female: 48:40) were eligible. Postoperative pathological results were as follows: seven cases of portal vein invasion; 81 cases without. Diagnostic accuracy of EUS, CH-EUS, and CE-CT for diagnosing invasion into the portal vein was 72.7%, 93.2%, and 81.8%, respectively. The differences between CH-EUS and CE-CT (P = 0.0094) and CH-EUS and EUS (P = 0.0022) were significant. EUS and CE-CT were comparable. Conclusion: CH-EUS is useful for diagnosis of portal vein invasion by pancreatic cancer.

＜文献概要＞▼急性膵炎と診断した後はまず重症化のリスクを判断し,重症化した場合,もしくは重症化が高率に予想される場合には適切な施設への搬送と適切な治療をシステマティックに行うことが求められ,「Pancreatitis Bundles 2021」の積極的活用が望まれる.▼「Pancreatitis Bundles 2021」で改訂された内容として,軽症急性膵炎には予防的抗菌薬は使用しないこと,経腸栄養は経胃でも可であること,感染性膵壊死に対するステップアップ・アプローチ,などがあげられる.▼急性膵炎診療における地域連携ネットワークの重要性は「急性膵炎診療ガイドライン2021」でも強調されており,各地域それぞれのネットワークづくりが求められる.▼急性胆管炎の診断には長らくCharcot 3徴(発熱・黄疸・腹痛)が用いられてきたが,実際にはCharcot 3徴をきたさない急性胆管炎が多く経験され,「急性胆管炎・胆嚢炎診療ガイドライン2018」では急性胆管炎の診断は「全身の炎症」「胆汁うっ滞」「胆管病変」の3因子を用いて行われている.▼急性膵炎・胆管炎,いずれの病態も重症度評価は頻回に行い,当初は軽症の症例でも重症化する可能性を常に念頭に置き,重症化のタイミングを逃さないようにすることが肝要である.

＜文献概要＞▼急性膵炎と診断した後はまず重症化のリスクを判断し,重症化した場合,もしくは重症化が高率に予想される場合には適切な施設への搬送と適切な治療をシステマティックに行うことが求められ,「Pancreatitis Bundles 2021」の積極的活用が望まれる.▼「Pancreatitis Bundles 2021」で改訂された内容として,軽症急性膵炎には予防的抗菌薬は使用しないこと,経腸栄養は経胃でも可であること,感染性膵壊死に対するステップアップ・アプローチ,などがあげられる.▼急性膵炎診療における地域連携ネットワークの重要性は「急性膵炎診療ガイドライン2021」でも強調されており,各地域それぞれのネットワークづくりが求められる.▼急性胆管炎の診断には長らくCharcot 3徴(発熱・黄疸・腹痛)が用いられてきたが,実際にはCharcot 3徴をきたさない急性胆管炎が多く経験され,「急性胆管炎・胆嚢炎診療ガイドライン2018」では急性胆管炎の診断は「全身の炎症」「胆汁うっ滞」「胆管病変」の3因子を用いて行われている.▼急性膵炎・胆管炎,いずれの病態も重症度評価は頻回に行い,当初は軽症の症例でも重症化する可能性を常に念頭に置き,重症化のタイミングを逃さないようにすることが肝要である.

Video 1A novel training method for endoscopic ultrasound operators, the Educational Program of Kindai system enables visualization of a trainee's learning curve and difficult-to-learn areas. This visualization helps both the trainer and the trainee to structure learning and teaching methods in real time.

＜文献概要＞胆道ジスキネジアは胆嚢,総胆管,十二指腸乳頭部に至る胆道系に器質的な病変が認められないにもかかわらず,右季肋部痛を主体とする胆石症様の腹部症状を呈する病態であり,Rome IV診断基準における機能性消化管障害の病型分類の"機能性胆嚢・Oddi乳頭括約筋障害(gallbladder and sphincter of Oddi disorder)"にあたる.問診により胆道痛の定義を満たすが,胆石,総胆管結石や他の器質的疾患を認めない症例のなかで,胆嚢がある症例にgallbladder disorderを疑い,胆嚢摘出後で血液検査にて肝酵素逸脱,もしくは画像検査にて胆管拡張を認める症例に胆道型乳頭括約筋機能異常(SOD)が疑われる.食事療法や生活習慣改善でも症状の改善が認められない場合に薬剤投与治療が施行され,薬物療法が無効な症例には内視鏡的乳頭切開術がおもに行われる.本病態は疑わなければ絶対に診断できない病態であるため,まず疑うことができるか,が最も重要なポイントとなる.

1969年に世界初の膵・胆道造影が日本で成功されてから50年が経ち、内視鏡的逆行性胆管膵管造影(endoscopic retrograde cholangiopancreatography:ERCP)は今や胆膵領域疾患において不可欠な診断・治療ツールとなっている。この50年の間には、たくさんのERCP関連デバイスの進歩があり、多様化が進み、専門的使用を念頭においた開発が進められている。われわれ胆膵内視鏡医には、日々アップデートしていくデバイス開発に精通し、各デバイスの開発意義と想定される使用イメージを理解し、眼前の患者にもっとも適したものを選択することが求められる。(著者抄録)

＜文献概要＞胆道ジスキネジアは胆嚢,総胆管,十二指腸乳頭部に至る胆道系に器質的な病変が認められないにもかかわらず,右季肋部痛を主体とする胆石症様の腹部症状を呈する病態であり,Rome IV診断基準における機能性消化管障害の病型分類の"機能性胆嚢・Oddi乳頭括約筋障害(gallbladder and sphincter of Oddi disorder)"にあたる.問診により胆道痛の定義を満たすが,胆石,総胆管結石や他の器質的疾患を認めない症例のなかで,胆嚢がある症例にgallbladder disorderを疑い,胆嚢摘出後で血液検査にて肝酵素逸脱,もしくは画像検査にて胆管拡張を認める症例に胆道型乳頭括約筋機能異常(SOD)が疑われる.食事療法や生活習慣改善でも症状の改善が認められない場合に薬剤投与治療が施行され,薬物療法が無効な症例には内視鏡的乳頭切開術がおもに行われる.本病態は疑わなければ絶対に診断できない病態であるため,まず疑うことができるか,が最も重要なポイントとなる.

Background and study aims  Endoscopic ultrasonography (EUS) is a reliable and efficient modality for detecting pancreatic tumors; however, plain EUS (P-EUS) is limited with respect to characterization of pancreatic tumors. Recently, the use of contrast-enhanced harmonic EUS (CH-EUS) has increased, and its utility for characterization of pancreatic tumors has been reported. This meta-analysis compares the diagnostic ability of P-EUS with that of CH-EUS for characterization of pancreatic tumors. Methods  A systematic meta-analysis of all potentially relevant articles in PubMed, the Cochrane library, and Google Scholar databases was performed. Fixed effects or random effects models were used to investigate pooled sensitivity, specificity, positive likelihood ratio, and negative likelihood ratio, with 95 % confidence intervals (CIs). Results  This meta-analysis included 719 patients who underwent CH-EUS and 723 who underwent P-EUS, from six eligible studies. The pooled estimates of sensitivity, specificity, and diagnostic odds ratio were 93 % (95 % CI, 0.90-0.95), 80 % (95 % CI, 0.75-0.85), and 57.9 (95 % CI, 25.9-130), respectively, for CH-EUS, and 86 % (95 % CI, 0.82-0.89), 59 % (95 % CI, 0.52-0.65), and 8.3 (95 % CI, 2.8-24.5) for P-EUS. The areas under the summary receiver operating characteristics curves for CH-EUS and P-EUS were 0.96 and 0.80, respectively. The diagnostic odds ratio for pancreatic cancer was 2.98 times higher on CH-EUS than on P-EUS ( P  = 0.03). Funnel plots demonstrated no publication bias. Conclusions  This meta-analysis demonstrates that CH-EUS has higher diagnostic accuracy for pancreatic cancer than P-EUS, and is thus a valuable tool for characterization of pancreatic tumors.

Fluoroscopy forms an essential part of endoscopic ultrasound-guided hepaticogastrostomy (EUS-HGS) and hepaticogastrostomy with antegrade stenting (EUS-HGAS). To date, no study has assessed and compared radiation exposure between EUS-HGS and EUS-HGAS. This study aimed to compare the radiation exposure parameters between EUS-HGS and EUS-HGAS. This retrospective single-center cohort study included consecutive patients who underwent EUS-HGS or EUS-HGAS from October 2017 to March 2019. The air kerma (AK: mGy), kerma-area product (KAP: Gycm2), fluoroscopy time (FT: min), and procedure time (PT: min) were assessed and compared between the two procedures. Altogether, 45 and 24 patients underwent EUS-HGS and EUS-HGAS, respectively. The median AK, KAP, FT, and PT were higher in the EUS-HGAS group than in the EUS-HGS group. A comparison revealed no difference in the technical success rate, complications rate, adverse event occurrence rate, and re-intervention rate between both procedures. This is the first report in which radiation exposure was used as a comparative parameter between EUS-HGS and EUS-HGAS. This study revealed that radiation exposure is significantly higher in EUS-HGAS than in EUS-HGS. Increased awareness on radiation exposure is warranted among gastroenterologists so that they choose the procedure with lower radiation exposure in cases where both procedures are indicated.

BACKGROUND AND AIM: Contrast-enhanced harmonic endoscopic ultrasonography (CH-EUS) is useful for the diagnosis of lesions inside and outside the digestive tract. This study evaluated the value of artificial intelligence (AI) in the diagnosis of gastric submucosal tumors by CH-EUS. METHODS: This retrospective study included 53 patients with gastrointestinal stromal tumors (GISTs) and leiomyomas, all of whom underwent CH-EUS between June 2015 and February 2020. A novel technology, SiamMask, was used to track and trim the lesions in CH-EUS videos. CH-EUS was evaluated by AI using deep learning involving a residual neural network and leave-one-out cross-validation. The diagnostic accuracy of AI in discriminating between GISTs and leiomyomas was assessed and compared with that of blind reading by two expert endosonographers. RESULTS: Of the 53 patients, 42 had GISTs and 11 had leiomyomas. Mean tumor size was 26.4 mm. The consistency rate of the segment range of the tumor image extracted by SiamMask and marked by the endosonographer was 96% with a Dice coefficient. The sensitivity, specificity, and accuracy of AI in diagnosing GIST were 90.5%, 90.9%, and 90.6%, respectively, whereas those of blind reading were 90.5%, 81.8%, and 88.7%, respectively (P = 0.683). The κ coefficient between the two reviewers was 0.713. CONCLUSIONS: The diagnostic ability of CH-EUS results evaluated by AI to distinguish between GISTs and leiomyomas was comparable with that of blind reading by expert endosonographers.

BACKGROUND: Pancreatic cancer (PC) exhibits extremely rapid growth; however, it remains largely unknown whether the early stages of PC also exhibit rapid growth speed equivalent to advanced PC. This study aimed to investigate the natural history of early PCs through retrospectively assessing pre-diagnostic images. METHODS: We examined the data of nine patients, including three patients with carcinoma in situ (CIS), who had undergone magnetic resonance cholangiopancreatography (MRCP) to detect solitary main pancreatic duct (MPD) stenosis >1 year before definitive PC diagnosis. We retrospectively analyzed the time to diagnosis and first-time tumor detection from the estimated time point of first-time MPD stenosis detection without tumor lesion. RESULTS: The median tumor size at diagnosis and the first-time tumor detection size were 14 and 7.5 mm, respectively. The median time to diagnosis and first-time tumor detection were 26 and 49 months, respectively. CONCLUSIONS: No studies have investigated the PC history, especially that of early PCs, including CIS, based on the initial detection of MPD stenosis using MRCP. Assessment of a small number of patients showed that the time to progression can take several years in the early PC stages. Understanding this natural history is very important in the clinical setting.

近年膵管内圧上昇による病態の治療として、外科的減圧治療、内視鏡的逆行性膵管ドレナージに加え、新たなドレナージ方法としてEUS下経消化管的膵管ドレナージ(EUS-PD)が報告されその有用性が報告されている。EUS-PDとは「胃や十二指腸から、EUSを用いて拡張膵管を描出し、EUS-FNAの要領で膵管にアクセスして内視鏡的にドレナージを行う手法」であるが、治療成績に関してはおおむね80%以上と高いものの手技成功率は63〜100%とばらつきがあり、最新のメタ解析では手技成功率は81.4%、臨床改善率は84.6%とされ、偶発症発症率は21.3%とされている。偶発症には出血や穿孔、頻度は低いながら重症膵炎なども報告されており、EUS-PDは同じEUS下ドレナージ治療であるEUS-BDと比較すると依然確立されていない適応を、慎重に検討する必要がある手技であると考えられる。本稿ではその適応と手技の実際について解説を行う。(著者抄録)

BACKGROUND: The value of contrast-enhanced harmonic endoscopic ultrasonography (CH-EUS) for T-staging in patients with extrahepatic bile duct cancer was evaluated. METHODS: This single-center, retrospective study included consecutive patients with extrahepatic bile duct cancer who underwent surgical resection after preoperative EUS, CH-EUS, and contrast-enhanced CT (CE-CT) examinations between June 2014 and August 2017. The capacity of these modalities for T-staging of extrahepatic bile duct cancer was evaluated by assessing invasion beyond the biliary wall into the surrounding tissue, gallbladder, liver, pancreas, duodenum, portal vein system (portal vein and/or superior mesenteric vein), inferior vena cava, and hepatic arteries (proper hepatic artery, right. and/or left. hepatic artery). Blind reading of EUS, CH-EUS, and CE-CT images was performed by two expert reviewers each. RESULTS: 38 patients were eligible for analysis, of which eight had perihilar bile duct cancer and 30 had distal bile duct cancer. Postoperative T-staging was T1 in 6, T2 in 16, and T3 in 16 cases. CH-EUS was superior to CE-CT for diagnosing invasion beyond the biliary wall into surrounding tissue (92.1% vs. 45.9%, P = 0.0002); the ability to detect invasion to other organs did not differ significantly between the two modalities. The accuracy of CH-EUS for T-staging of tumors was better than that of CE-CT (73.7% vs. 39.5%, P = 0.0059). CH-EUS tended to have a better accuracy than EUS for the diagnosis of invasion beyond the biliary wall into the surrounding tissue (92.1% vs. 78.9%, P = 0.074) and T-staging (73.7% vs. 60.5%, P = 0.074). CONCLUSION: CH-EUS is useful for T-staging of extra hepatic bile duct cancer, especially in terms of invasion beyond the biliary wall into the surrounding tissue.

Due to the tendency of gastric linitis plastica (GLP) to cause extensive submucosal infiltration, a superficial endoscopic biopsy sometimes yields no evidence of malignancy, hindering definite diagnosis. The present study was a single-center retrospective analysis of 54 consecutive patients diagnosed with GLP between 2016 and 2020 to evaluate EUS-guided fine-needle aspiration (EUS-FNA) biopsy outcomes in patients with negative endoscopic biopsy findings. A pathological GLP diagnosis was achieved by endoscopic biopsy in 40 patients (74.1%). EUS-FNA biopsy with a 22-gauge needle was performed in 13 of the remaining 14 patients, and GLP diagnosis was confirmed in 10 patients, with a median of three needle passes. The remaining four patients were laparoscopically diagnosed with GLP. The diagnostic ability of EUS-FNA biopsy for GLP was 76.9%, and EUS-FNA biopsy contributed to GLP diagnosis in 18.5% (10/54) of all cases. None of the 13 patients exhibited EUS-FNA biopsy-related adverse events. Univariable and multivariable analyses revealed an absence of superficial ulcerations as a predictor of false-negative endoscopic biopsy findings in patients with GLP. These results suggest EUS-FNA biopsy as a minimally invasive and safe alternative diagnostic modality for GLP in cases where conventional endoscopic biopsy fails to verify malignancy, although prospective studies with larger cohorts are warranted to confirm these findings.

BACKGROUND AND AIMS: Pancreatic neuroendocrine neoplasms (PanNENs), including Grade 1 (G1) or G2 tumors, can have a poor prognosis. This study investigated the value of contrast-enhanced harmonic endoscopic ultrasonography (CH-EUS) for predicting the prognosis of PanNENs. METHODS: This single-center, retrospective study included 47 consecutive patients who underwent CH-EUS and were diagnosed with PanNEN by surgical resection or EUS-guided fine needle aspiration between December 2011 and February 2016. Patients were divided into aggressive and non-aggressive groups according to the degree of clinical malignancy. CH-EUS was assessed regarding its capacity for diagnosing aggressive PanNEN, the correspondence between contrast patterns and pathological features, and its ability to predict the prognosis of PanNEN. RESULTS: There were 19 cases of aggressive PanNEN and 28 cases of non-aggressive PanNEN. The aggressive group included three G1, four G2, three G3 tumors, three mixed neuroendocrine non-neuroendocrine neoplasms, and six neuroendocrine carcinomas. CH-EUS was superior to contrast-enhanced computed tomography for the diagnosis of aggressive PanNEN (P < 0.001): hypo-enhancement on CH-EUS was an indicator of aggressive PanNEN, with sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of 94.7%, 100%, 100%, 96.6%, and 97.9%, respectively. Among G1/G2 PanNENs, cases with hypo-enhancement on CH-EUS had a poorer prognosis than those with hyper/iso-enhancement (P = 0.0009). Assessment of 36 resected specimens showed that hypo-enhancement on CH-EUS was associated with smaller and fewer vessels and greater degree of fibrosis. CONCLUSION: Contrast-enhanced harmonic endoscopic ultrasonography may be useful for predicting the prognosis of PanNENs.

Unsuccessful stent replacement in transpapillary biliary drainage with plastic stents (PSs) has a significant impact on patient prognosis; thus, a safe and reliable replacement method is required. We aimed to compare the snare-over-the-guidewire (SOG) method, wherein the PS lumen is used as an access route to the biliary tract and the PS is removed with a snare inserted via the inserted guidewire, with the conventional side-of-stent (SOS) method, wherein the biliary approach is performed from the side of the PS. This retrospective single-center study included 244 consecutive patients who underwent biliary PS replacement between January 2018 and July 2020. The procedural success rates were compared between the two methods. A predictive analysis of unsuccessful PS replacement was also performed. The procedural success rate in the SOG group was significantly higher than that in the SOS group (p = 0.026). In the proximal biliary stenosis lesion, the same trend was observed (p = 0.025). Multivariate analysis also showed that the SOS method (p = 0.0038), the presence of proximal biliary stenosis (p < 0.0001), and parapapillary diverticulum (p = 0.0007) were predictors of unsuccessful PS replacement. The SOG method may be useful for biliary PS replacement, especially in cases of proximal hilar bile duct stenosis.

BACKGROUND AND AIM: Bilateral stent deployment for malignant biliary obstruction (MHBO) can be achieved using side-by-side (SBS) or stent-in-stent (SIS) procedures. Compared with SBS techniques, the procedural steps of SIS are technically complex due to the necessity of introducing the delivery system into a contralateral biliary tract through the mesh of the SEMS. To overcome this issue, a novel uncovered SEMS, the HILZO Moving Cell Stent (MCS) has been released. The present study examined the technical feasibility of treating MHBO using bilateral deployment of this novel stent without dilating the mesh of the first stent to achieve insertion of the second stent within a single session, using a prospective, multicenter setting. METHOD: The primary outcome in the present study was the technical success rate. Technical success was defined as deployment of bilateral MCSs into two or more biliary tracts using SIS without a dilation device in a single-session. RESULTS: A total of 27 patients with complications of MHBO were enrolled in this study. Bilateral SIS using two MCS was successfully performed in 23 patients without using dilation devices among 27 patients (initial technical success rate; 85.2%). Median time to recurrent biliary obstruction (TRBO) was 271 days. Stent dysfunction was observed in 12 patients (44.4%), and re-intervention was successfully performed in all patients without one patient who instead received best supportive care. CONCLUSIONS: The SIS technique using MCS without dilation of the mesh may be technically feasible and safe. In addition, this may be useful for re-intervention. Further comparative randomized trials are needed.

OBJECTIVES: The transpapillary drainage by endoscopic retrograde cholangiopancreatography (ERCP-D) cannot be performed without fluoroscopy, and there are many situations in which fluoroscopy is required even in endoscopic ultrasound-guided drainage (EUS-D). Previous studies have compared the efficacy, but not the radiation exposure of EUS-D and ERCP-D. While radiation exposure in ERCP-D has been previously evaluated, there is a paucity of information regarding radiation doses in EUS-D. This study aimed to assess radiation exposure in EUS-D compared with that in ERCP-D. METHODS: This retrospective single-center cohort study included consecutive patients who underwent EUS-D and ERCP-D between October 2017 and March 2019. The air kerma (AK: mGy), kerma-area product (KAP: Gycm2 ), fluoroscopy time (FT: min), and procedure time (PT: min) were assessed. The invasive probability weighting method was used to qualify the comparisons. RESULTS: We enrolled 372 and 105 patients who underwent ERCP-D and EUS-D, respectively. The mean AK, KAP, and FT in the EUS-D group were higher by 53%, 28%, and 27%, respectively, than those in the ERCP-D group, whereas PT was shorter by approximately 11% (AK; 135.0 vs. 88.4, KAP; 28.1 vs. 21.9, FT; 20.4 vs. 16.0, PT; 38.7 vs. 43.5). The sub-analysis limited to biliary drainage cases showed the same trend (AK; 128.3 vs. 90.9, KAP; 27.0 vs. 22.2, FT; 16.4 vs. 16.1, PT; 32.5 vs. 44.4). CONCLUSIONS: This is the first study to assess radiation exposure in EUS-D compared with that in ERCP-D. Radiation exposure was significantly higher in EUS-D than in ERCP-D, despite the shorter procedure time.

BACKGROUND AND AIM: Recombinant thrombomodulin (rhTM) is potentially effective in the treatment of disseminated intravascular coagulation (DIC). Several studies related to drugs for the treatment of acute cholangitis have shown negative results in improvement of overall survival (OS) with rhTM. The aim of this multicenter study was to evaluate the clinical effectiveness of rhTM in patients with acute cholangitis and sepsis-induced DIC who underwent biliary drainage. METHODS: A total of 284 consecutive patients, who were complicated with sepsis-induced DIC due to severe acute cholangitis, were included (rhTM group, n = 173; non-rhTM, n = 111) in this study. The primary outcome was the DIC resolution rate at 7 days after starting treatment. The 28-day survival rate was secondarily evaluated. RESULTS: DIC scores in the rhTM group improved significantly compared with the non-rhTM group on day 7 (P = .020). According to multivariate analysis, etiology of cholangitis (malignant, HR 2.28), rhTM (non-administration, HR 4.13), and DIC score (≥5, HR 2.46) were significant factors associated with failed DIC resolution on day 7. Propensity score matching created 103 matched pairs. Survival rate at day 28 was significantly higher in rhTM group (94.3%) compared with non-rhTM group (82.6%; P = .048) after propensity score matching. rhTM (non-administration, HR 2.870), DIC score (≥5, HR 2.751), and APACHE II score (≥20, HR 9.310) were significant factors associated with decreasing survival rate at day 28. CONCLUSION: In conclusion, rhTM seemed to improve patient survival, but future studies should only include patients with benign or malignant disease and should be performed according to APACHE II scores.

This study aimed to investigate whether the incorporation of contrast-enhanced harmonic endoscopic ultrasound (CH-EUS) into the international consensus guidelines (ICG) for the management of intraductal papillary mucinous neoplasm (IPMN) could improve its malignancy diagnostic value. In this single-center retrospective study, 109 patients diagnosed with IPMN who underwent preoperative CH-EUS between March 2010 and December 2018 were enrolled. We analyzed each malignancy diagnostic value (sensitivity (Se), specificity (Sp), positive predictive value (PPV), and negative predictive value (NPV)) by replacing fundamental B-mode EUS with CH-EUS as the recommended test for patients with worrisome features (WF) (the CH-EUS incorporation ICG) and comparing the results to those obtained using the 2017 ICG. The malignancy diagnostic values as per the 2017 ICG were 78.9%, 42.3%, 60.0%, and 64.7% for Se, Sp, PPV, and NPV, respectively. The CH-EUS incorporation ICG plan improved the malignancy diagnostic values (Se 78.9%/Sp, 53.8%/PPV, 65.2%/NPV 70.0%). CH-EUS may be useful in determining the appropriate treatment strategies for IPMN.

OBJECTIVES: This prospective multicenter study aimed to assess and compare the accuracy of tissue harmonic endoscopic ultrasonography (TH-EUS) and contrast-enhanced harmonic endoscopic ultrasonography (CH-EUS) for differentiating pancreatic carcinoma from other pancreatic tumors. METHODS: Consecutive patients with solid pancreatic tumors were prospectively enrolled between August 2013 and December 2014. To assess the accuracy of TH-EUS and CH-EUS, we compared four parameters of TH-EUS (fuzzy edge, irregular periphery, hypoechogenicity, and heterogeneous internal echogenicity) and four parameters of CH-EUS (hypoenhancement and heterogeneous enhancement in the early and late phases, respectively) to investigate which parameter of each method was most suitable to diagnose pancreatic carcinomas. Interobserver agreement and the diagnostic ability of pancreatic carcinoma using TH-EUS and CH-EUS were assessed and compared. RESULTS: A total of 204 patients were enrolled. For the diagnosis of pancreatic carcinoma, interobserver agreement by experts and nonexperts was 0.33-0.50 and 0.35-0.50 for TH-EUS, respectively, and 0.72-0.74 and 0.20-0.54 for CH-EUS, respectively. Irregular periphery was the most accurate diagnostic parameter among TH-EUS findings for differentiating pancreatic carcinomas, with sensitivity, specificity, and accuracy of 95.0%, 42.9%, and 78.9%, respectively. Late phase hypoenhancement was the most accurate diagnostic parameter among CH-EUS findings for differentiating pancreatic carcinomas, with sensitivity, specificity, and accuracy of 90.8%, 74.6%, and 85.8%, respectively. The accuracy of CH-EUS (late phase hypoenhancement) for diagnosis of pancreatic carcinoma was significantly higher than that of TH-EUS (irregular periphery) (p < 0.001). CONCLUSION: In comparison with TH-EUS, CH-EUS increased the diagnostic ability and reproducibility for the diagnosis of pancreatic carcinoma. UMIN (000011124).

BACKGROUND AND AIMS: Kupffer-phase imaging visualized by perfluorobutane (Sonazoid) distribution into normal liver tissues upon phagocytosis by Kupffer cells potentially aids in improving detection of liver metastasis compared with fundamental B-mode EUS (FB-EUS). However, the diagnostic performance of Kupffer-phase imaging in contrast-enhanced harmonic EUS (CH-EUS) remains unclear. Hence, this study aimed to evaluate the usefulness of CH-EUS-based Kupffer-phase imaging for diagnosing liver metastasis from pancreatic cancer. METHODS: We retrospectively analyzed consecutive patients with pancreatic cancer who underwent contrast-enhanced CT (CE-CT) and FB-EUS, followed by CH-EUS, from 2011 to 2017. The diagnostic ability of CH-EUS against that of CE-CT and FB-EUS for metastasis in the left liver lobe was compared. Subsequently, the influences of CH-EUS on the determination of clinical stage and patient management for pancreatic cancer were assessed. RESULTS: We enrolled 426 patients with pancreatic cancer. Metastasis in the left liver lobe was present in 27.2% of patients. The diagnostic accuracy of CE-CT, FB-EUS, and CH-EUS was 90.6%, 93.4%, and 98.4%, respectively. The sensitivity and diagnostic accuracy of CH-EUS for metastasis in the left liver lobe were significantly higher than those of FB-EUS or CE-CT. The sensitivity of CH-EUS for detecting small liver metastasis (<10 mm) was considerably higher than that of CE-CT or FB-EUS (P < .001). In 2.1% of patients, only CH-EUS could detect a single distant metastasis of the left liver lobe, thereby upgrading the tumor staging and altering the clinical management. CONCLUSIONS: CH-EUS-based Kupffer-phase imaging increased the detectability of metastasis in the left liver lobe. This technique could be a reliable pretreatment imaging modality for clinical decision-making in patients with pancreatic cancer.

IgG4-related disease (IgG4-RD) is a multi-organ autoimmune disease characterized by elevated serum IgG4 concentration. Although serum IgG4 concentration is widely used as a biomarker for IgG4-RD and type 1 autoimmune pancreatitis (AIP), a pancreatic manifestation of IgG4-RD, a significant number of patients have normal serum IgG4 levels, even in the active phase of the disease. Recently, we reported that the development of experimental AIP and human type 1 AIP is associated with increased expression of IFN-α and IL-33 in the pancreas. In this study, we assessed the utility of serum IFN-α and IL-33 levels as biomarkers for type 1 AIP and IgG4-RD. Serum IFN-α and IL-33 concentrations in patients who met the diagnostic criteria for definite type 1 AIP and/or IgG4-RD were significantly higher than in those with chronic pancreatitis or in healthy controls. Strong correlations between serum IFN-α, IL-33, and IgG4 concentrations were observed. Diagnostic performance of serum IFN-α and IL-33 concentrations as markers of type 1 AIP and/or IgG4-RD was comparable to that of serum IgG4 concentration, as calculated by the receiver operating characteristic curve analysis. Induction of remission by prednisolone treatment markedly decreased the serum concentration of these cytokines. We conclude that serum IFN-α and IL-33 concentrations can be useful as biomarkers for type 1 AIP and IgG4-RD.

BACKGROUND: This study aimed to evaluate and identify the specific CT findings by focusing on abnormalities in the main pancreatic duct (MPD) and pancreatic parenchyma in patients with small pancreatic cancer (PC) including carcinoma in situ (CIS). METHODS: Nine CT findings indicating abnormalities of MPD and pancreatic parenchyma were selected as candidate findings for the presence of small PC ≤ 10 mm. The proportions of patients positive for each finding were compared between small PC and benign MPD stenosis groups. Interobserver agreement between two independent image reviewers was evaluated using kappa statistics. RESULTS: The final analysis included 24 patients with small PC (including 11 CIS patients) and 28 patients with benign MPD stenosis. The proportion of patients exhibiting partial pancreatic parenchymal atrophy (PPA) corresponding to the distribution of MPD stenosis (45.8% vs. 7.1%, p < 0.01), upstream PPA arising from the site of MPD stenosis (33.3% vs. 3.6%, p = 0.01), and MPD abrupt stenosis (45.8% vs. 14.3%, p = 0.03) was significantly higher in the small PC group than in the benign MPD stenosis group. CONCLUSIONS: The presence of partial PPA, upstream PPA, and MPD abrupt stenosis on a CT image was highly suggestive of the presence of small PCs including CIS.

OBJECTIVE: The optimal management of acute cholecystitis in patients at very high risk for cholecystectomy is uncertain. The aim of the current study was to compare endoscopic ultrasound (EUS)-guided gallbladder drainage (EUS-GBD) to percutaneous cholecystostomy (PT-GBD) as a definitive treatment in these patients under a randomised controlled trial. DESIGN: Consecutive patients suffering from acute calculous cholecystitis but were at very high-risk for cholecystectomy were recruited. The primary outcome was the 1-year adverse events rate. Secondary outcomes include technical and clinical success, 30-day adverse events, pain scores, unplanned readmissions, re-interventions and mortalities. RESULTS: Between August 2014 to February 2018, 80 patients were recruited. EUS-GBD significantly reduced 1 year adverse events (10 (25.6%) vs 31 (77.5%), p<0.001), 30-day adverse events (5 (12.8%) vs 19 (47.5%), p=0.010), re-interventions after 30 days (1/39 (2.6%) vs 12/40 (30%), p=0.001), number of unplanned readmissions (6/39 (15.4%) vs 20/40 (50%), p=0.002) and recurrent cholecystitis (1/39 (2.6%) vs 8/40 (20%), p=0.029). Postprocedural pain scores and analgesic requirements were also less (p=0.034). The technical success (97.4% vs 100%, p=0.494), clinical success (92.3% vs 92.5%, p=1) and 30-day mortality (7.7% vs 10%, p=1) were statistically similar. The predictor to recurrent acute cholecystitis was the performance of PT-GBD (OR (95% CI)=5.63 (1.20-53.90), p=0.027). CONCLUSION: EUS-GBD improved outcomes as compared to PT-GBD in those patients that not candidates for cholecystectomy. EUS-GBD should be the procedure of choice provided that the expertise is available after a multi-disciplinary meeting. Further studies are required to determine the long-term efficacy. TRIAL REGISTRATION NUMBER: NCT02212717.

BACKGROUND: Although several techniques for endoscopic ultrasound-guided biliary drainage (EUS-BD) are available at present, an optimal treatment algorithm of EUS-BD has not yet been established. AIM: To evaluate the clinical utility of treatment method conversion during single endoscopic sessions for difficult cases in initially planned EUS-BD. METHODS: This was a single-center retrospective analysis using a prospectively accumulated database. Patients with biliary obstruction undergoing EUS-BD between May 2008 and April 2016 were included. The primary outcome was to evaluate the improvement in EUS-BD success rates by converting the treatment methods during a single endoscopic session. Secondary outcomes were clarification of the factors leading to the conversion from the initial EUS-BD and the assessment of efficacy and safety of the conversion as judged by technical success, clinical success, and adverse events (AEs). RESULTS: A total of 208 patients underwent EUS-BD during the study period. For 18.8% (39/208) of the patients, the treatment methods were converted to another EUS-BD technique from the initial plan. Biliary obstruction was caused by pancreatobiliary malignancies, other malignant lesions, biliary stones, and other benign lesions in 22, 11, 4, and 2 patients, respectively. The reasons for the difficulty with the initial EUS-BD were classified into the following 3 procedures: Target puncture (n = 13), guidewire manipulation (n = 18), and puncture tract dilation (n = 8). Technical success was achieved in 97.4% (38/39) of the cases and clinical success was achieved in 89.5% of patients (34/38). AEs occurred in 10.3% of patients, including bile leakage (n = 2), bleeding (n = 1), and cholecystitis (n = 1). The puncture target and drainage technique were altered in subsequent EUS-BD procedures in 25 and 14 patients, respectively. The final technical success rate with 95%CI for all 208 cases was 97.1% (95%CI: 93.8%-98.9%), while that of the initially planned EUS-BD was 78.8% (95%CI: 72.6%-84.2%). CONCLUSION: Among multi-step procedures in EUS-BD, guidewire manipulation appeared to be the most technically challenging. When initially planned EUS-BD is technically difficult, treatment method conversion in a single endoscopic session may result in successful EUS-BD without leading to severe AEs.

BACKGROUND: Balloon enteroscopy-assisted endoscopic retrograde cholangiopancreatography (BE-ERCP) has been reported to be effective for patients with surgically altered gastrointestinal anatomy. However, selective biliary cannulation remains difficult in BE-ERCP. We examined the usefulness of a modified double-guidewire technique using an uneven double lumen cannula (the uneven method) for BE-ERCP in patients with surgically altered gastrointestinal anatomy. METHODS: To clarify the usefulness of the uneven method for selective biliary cannulation in BE-ERCP in comparison to the pancreatic guidewire (PGW) method, 40 patients with surgically altered gastrointestinal anatomy who underwent BE-ERCP with successful placement of a guidewire in the pancreatic duct were evaluated. The uneven method was used in 18 cases (uneven group) and the PGW method was used in the remaining 22 cases (PGW group). RESULTS: The technical success rate of biliary cannulation was higher in the uneven group than in the PGW group (83.3 vs. 59.0%; P = 0.165). In addition, the time to biliary cannulation were significantly shorter in the uneven group than in the PGW group (6 vs. 18 min; P = 0.004; respectively). In the PGW group, post-ERCP pancreatitis (PEP) occurred in 3 of 22 cases (13.6%). No adverse events, including PEP, occurred in the uneven group. CONCLUSIONS: The uneven method may be a useful option of selective biliary cannulation in BE-ERCP for the patients with surgically altered gastrointestinal anatomy.

内視鏡的逆行性胆管膵管造影検査(ERCP)の医療従事者を対象に、水晶体被曝線量計を左右内外4ヶ所に装着した防護メガネを作成し、立ち位置別の水晶体被曝線量を測定した。その結果、全立ち位置でX線管球に最も距離が近い左眼の被曝線量が高く、外側の平均値1.4mSv、内側の平均値0.73mSvであった。最大線量測定値は7月の術者左側外側の1.5mSvであった。以上より、術者の左眼水晶体の年間被曝線量は16.8mSv(1.4mSv×12ヵ月)と推定され、ICRP勧告である20mSv/年に近かった。防護メガネ外側の水晶体被曝線量は防護メガネを装着しない場合の値と近似すると推定され、ERCPなどの放射線透視処置に関わる医療従事者は、被曝防護メガネ着用の徹底が必要であると考えられた。

BACKGROUND AND AIMS: Contrast-enhanced harmonic endoscopic ultrasonography (CH-EUS) is used for the diagnosis of pancreatic cancer (PC). Here, we examined the usefulness of CH-EUS for evaluating therapeutic responses in PC. METHODS: The study included 23 patients with PC who received chemotherapy. Patients underwent contrast-enhanced computed tomography (CE-CT) and CH-EUS before chemotherapy and at the time of evaluation of the therapeutic response. Patients with a ≧50% reduction in serum carbohydrate antigen 19-9 levels after chemotherapy were defined as "super responders". The incidence of an avascular area in the tumor on CH-EUS after chemotherapy was compared between "super responders" and non-super responders. RESULTS: Nine patients were included in the "super responders" group.Tumor reduction rates did not differ significantly between CE-CT and CH-EUS in the "super responders". The appearance of an avascular area was detected in 7 of 9 super responders (77.8%) and in 4 of 14 non-super responders (28.6%), and the difference was significant (P = 0.036). The mean survival time of patients with an avascular area after chemotherapy was longer than that of without an avascular area. CONCLUSIONS: Detection of avascular areas by CH-EUS after chemotherapy may predict long-term survival of patients with PC.

Objective Although modified FOLFIRINOX (mFOLFIRINOX, mFFX) is widely used for patients with advanced pancreatic ductal adenocarcinoma (PDAC), maintenance of the standard dose intensity is often difficult due to the high incidence of neutropenic events. Pegylated granulocyte colony-stimulating factor (G-CSF) (Peg G) is a long-lasting G-CSF agent that is applicable for prophylaxis against neutropenic complications. The aim of this study was to assess the clinical safety and efficacy of mFFX combined with secondary prophylaxis using Peg G in advanced PDAC patients. Methods Advanced PDAC patients who had received more than two cycles of mFFX were analyzed. The clinical safety and efficacy were compared between patients in the Peg G group and those in the non-Peg G group in a retrospective manner. Results Among 45 patients treated with mFFX, 28 exhibited grade 3-4 neutropenia or febrile neutropenia. Among these 28 patients, 4 who received only 1 or 2 mFFX cycles were excluded from this study. Finally, 11 patients in the Peg G group and 13 in the non-Peg G group were enrolled. The combination therapy with Peg G and mFFX markedly prolonged the progression-free survival compared with the non-Peg G group, and its effects were associated with a reduced incidence of neutropenic events as well as lower rates of dosage reduction, delayed chemotherapy due to neutropenic events and altered blood cell counts after chemotherapy. Conclusion The scheduled administration of secondary prophylactic Peg G prolonged the progression-free survival in patients treated with mFFX. The combination therapy of Peg G and mFFX may be recommended in patients who exhibit grade 3-4 neutropenic events after prior mFFX cycles.

Background and Aim: This study evaluated the utility of endoscopic ultrasonography (EUS) combined with contrast-enhanced harmonic EUS (CH-EUS) for surveillance of the remnant pancreas after surgery for intraductal papillary mucinous neoplasm (IPMN). Methods: This was a single-center, retrospective, descriptive study. A total of 134 consecutive patients who underwent surgical resection for IPMN between April 2009 and March 2015 were evaluated. Rates of recurrence and development of IPMN-concomitant pancreatic ductal adenocarcinoma (PDAC) during follow up were assessed. Clinical findings of patients with recurrence or development of PDAC were also evaluated. Results: Of 134 resected IPMN 56 (41.8%) and 78 (58.2%) were classified as benign and malignant, respectively. Patients were followed up for a median of 29 months, 33 (24.6%) by both contrast-enhanced computed tomography (CE-CT) and EUS, and 101 (75.4%) by computed tomography (CT) alone. Thirteen patients (9.7%) showed tumor recurrence, five with intra-pancreatic recurrence and eight with extra-pancreatic metastases. An enhancing mural nodule within the dilated main pancreatic duct was successfully detected by EUS in one patient, but not by CE-CT. Two patients developed IPMN-concomitant PDAC during follow up. EUS combined with CH-EUS successfully detected small IPMN-concomitant PDAC in two patients, whereas these lesions were not detected by CT. CH-EUS was useful for better visualization of the margins of IPMN-concomitant PDAC in one of these two patients. Conclusion: Endoscopic ultrasonography combined with CH-EUS may improve follow up of patients with resected IPMN.

Neurilemmomas are benign tumors arising from the sheaths of peripheral nerves. They appear rarely in the abdominal cavity. We herein report an 80-year-old man with a multilocular cystic neurilemmoma mimicking a liver lesion. Preoperative images showed a lesion in the porta hepatis. Although a preoperative diagnosis was difficult, surgery was undertaken because of the possibility of malignancy. Histologically, the tumor consisted of spindle-shaped cells with positivity for S-100 protein. The final diagnosis was a neurilemmoma. Porta hepatic neurilemmomas are rare. When we encounter a multilocular cystic lesion of the liver, neurilemmoma should be considered in the differential diagnosis.

＜文献概要＞EUSは上部消化管粘膜下腫瘍(SMT)の診断に用いられているが,上部消化管SMTの良悪性鑑別には限界がある.本稿では,造影ハーモニックEUSによる上部消化管粘膜下腫瘍の診断に関する前向き研究1報と後ろ向き研究6報の合計7報の研究をもとに上部消化管SMTの鑑別診断について調べた.造影ハーモニックEUSによるGISTとそれ以外の上部消化管SMTの鑑別診断に関する3つの報告では,hyper-enhancementがGISTの造影ハーモニックEUS所見であり,診断能は感度84.5〜100%,特異度73.3〜100%であった.一方,low-grade malignancy GISTとhigh-grade malignancy GISTの鑑別診断に関する4つの報告では,造影ハーモニックEUSによるhigh-grade malignancy GISTの診断能は感度53.8〜100%,特異度63〜100%であった.またhigh-grade malignancy GISTでは造影ハーモニックEUSにおいてirregular vesselsが高率に認められた.hyper-enhancementか否かおよびirregular vesselsの有無を確認することで上部消化管SMTの鑑別診断が可能であることが示唆された.

Copyright© 2018 Japan Gastroenterological Endoscopy Society. All rights reserved. Background and Aim: Differential diagnosis of localized gallbladder lesions is challenging. The aim of the present study was to evaluate the utility of contrast-enhanced harmonic endoscopic ultrasonography (CH-EUS) for diagnosis of localized gallbladder lesions. Methods: One hundred and twenty-five patients with localized gallbladder lesions were evaluated by CH-EUS between March 2007 and February 2014. This was a single-center retrospective study. Utilities of fundamental B-mode EUS (FB-EUS) and CH-EUS in the differentiation of gallbladder lesions and sludge plug were initially compared. Thereafter, these two examinations were compared with respect to their accuracy in the diagnosis of malignant lesions. Five reviewers blinded to the clinicopathological results evaluated microcirculation patterns in the vascular and perfusion images. Results: In the differentiation between gallbladder lesions and sludge plug, FB-EUS had a sensitivity, specificity, and accuracy of 82％, 100％, and 95％, respectively, whereas CH-EUS had a sensitivity, specificity, and accuracy of 100％, 99％, and 99％, respectively. FB-EUS-based diagnosis of carcinomas based on tumor size and/or shape had a sensitivity, specificity, and accuracy of 61-87％, 71-88％, and 74-86％, respectively. Additional information regarding irregular vessel patterns in the vascular image and/or heterogeneous enhancement in the perfusion image on CH-EUS increased the sensitivity, specificity, and accuracy for the diagnosis of carcinomas to 90％, 98 ％, and 96％, respectively. There was a significant difference between FB-EUS and CH-EUS in terms of carcinoma diagnosis. Conclusion: CH-EUS was useful for the evaluation of localized gallbladder lesions.

BACKGROUND AND AIM: This study evaluated the utility of endoscopic ultrasonography (EUS) combined with contrast-enhanced harmonic EUS (CH-EUS) for surveillance of the remnant pancreas after surgery for intraductal papillary mucinous neoplasm (IPMN). METHODS: This was a single-center, retrospective, descriptive study. A total of 134 consecutive patients who underwent surgical resection for IPMN between April 2009 and March 2015 were evaluated. Rates of recurrence and development of IPMN-concomitant pancreatic ductal adenocarcinoma (PDAC) during follow up were assessed. Clinical findings of patients with recurrence or development of PDAC were also evaluated. RESULTS: Of 134 resected IPMN 56 (41.8%) and 78 (58.2%) were classified as benign and malignant, respectively. Patients were followed up for a median of 29 months, 33 (24.6%) by both contrast-enhanced computed tomography (CE-CT) and EUS, and 101 (75.4%) by computed tomography (CT) alone. Thirteen patients (9.7%) showed tumor recurrence, five with intra-pancreatic recurrence and eight with extra-pancreatic metastases. An enhancing mural nodule within the dilated main pancreatic duct was successfully detected by EUS in one patient, but not by CE-CT. Two patients developed IPMN-concomitant PDAC during follow up. EUS combined with CH-EUS successfully detected small IPMN-concomitant PDAC in two patients, whereas these lesions were not detected by CT. CH-EUS was useful for better visualization of the margins of IPMN-concomitant PDAC in one of these two patients. CONCLUSION: Endoscopic ultrasonography combined with CH-EUS may improve follow up of patients with resected IPMN.

OBJECTIVES: Pancreatic metastases (PMs) account for 1% to 2% of pancreatic tumors, and their prognostic significance is poorly defined. We evaluated the incidence and clinical characteristics of primary tumors and defined prognostic factors. METHODS: This retrospective study of 39 Japanese tertiary referral hospitals (January 2005 to August 2015) analyzed patient and tumor characteristics and survival time. Kaplan-Meier analysis and Cox proportional hazards models were applied to evaluate overall survival and prognostic factors, respectively. RESULTS: We enrolled 159 patients with a pathologic diagnosis of PM. The most common primary tumor was renal cell carcinoma (38.4%), followed by lung cancer (24.5%), colorectal cancer (11.3%), and sarcoma (6.3%). Eight patients were lost during follow-up, and 151 patients were included for statistical analysis. Median overall survival was 43.0 months, and the 5-year survival rate was 42.6%. Multivariate analysis identified 3 independent prognostic factors: extrapancreatic metastasis (hazard ratio, 2.13; 95% confidence interval, 1.11-4.07; P = 0.02), tumor-related symptoms at diagnosis (hazard ratio, 5.39; 95% confidence interval, 2.92-9.91; P < 0.001), and pathologic diagnosis of primary tumors (P < 0.001). CONCLUSIONS: Treatment strategies and prognoses for PMs completely differ according to the primary tumor type. A definitive pathologic diagnosis of PMs is essential for selecting the appropriate treatment.

The most common symptom in patients with advanced pancreatic cancer is abdominal pain. This has traditionally been treated with nonsteroidal anti-inflammatory drugs and opioid analgesics. However, these treatments result in inadequate pain control or drug-related adverse effects in some patients. An alternative pain-relief modality is celiac plexus neurolysis, in which the celiac plexus is chemically ablated. This procedure was performed percutaneously or intraoperatively until 1996, when endoscopic ultrasound (EUS)-guided celiac plexus neurolysis was first described. In this transgastric anterior approach, a neurolytic agent is injected around the celiac trunk under EUS guidance. The procedure gained popularity as a minimally invasive approach and is currently widely used to treat pancreatic cancer-associated pain. We focus on two relatively new techniques of EUS-guided neurolysis: EUS-guided celiac ganglia neurolysis and EUS-guided broad plexus neurolysis, which have been developed to improve efficacy. Although the techniques are safe and effective in general, some serious adverse events including ischemic and infectious complications have been reported as the procedure has gained widespread popularity. We summarize reported clinical outcomes of EUS-guided neurolysis in pancreatic cancer (from the PubMed and Embase databases) with a goal of providing information useful in developing strategies for pancreatic cancer-associated pain alleviation.

膵・胆管合流異常に合併した共通管内乳頭状腫瘍の1例を報告する.症例は75歳の男性で,6ヵ月間に2度の急性膵炎を発症し保存的加療で軽快した.急性膵炎の原因精査および加療目的で当院へ紹介となった.ERCPでは膵・胆管合流異常を認め,共通管内に7mmの結節様陰影欠損像を認めた.上部内視鏡検査では乳頭部からの粘液排出は認めず,超音波内視鏡検査では共通管内に乳頭状の腫瘍が描出された.造影CTでは膵頭部に拡張した共通管と内部に増強効果を持つ8mmの腫瘤を認めた.尾側の主膵管の拡張は認めなかった.膵・胆管合流異常に合併した共通管内乳頭状腫瘍と診断し,亜全胃温存膵頭十二指腸切除術を施行した.病理肉眼所見では共通管内に発育する有茎性の乳頭状腫瘍で,組織像は管状構造増生を主体とする腺腫であった.免疫組織学的染色ではMUC1,MUC2陰性,MUC5AC陽性で胃型腺腫と最終診断した.(著者抄録)

We report a case of successful transluminal drainage of walled-off necrosis (WON) under contrast-enhanced harmonic endoscopic ultrasonography (CH-EUS) guidance. Recently, EUS-guided transluminal drainage (EUS-TD) of WON has been increasingly used as a minimally invasive treatment option with reportedly high technical and clinical success rates; however, B-mode EUS occasionally fails to depict the target lesion and its margins, particularly in cases where the target shows a heterogeneous echogenicity. In our case, EUS-TD was attempted for infected WON, but visualization using B-mode EUS imaging was poor. Thus, CH-EUS was performed to enhance the contrast between the targeted WON and its surrounding tissues. Immediately after injecting a sonographic contrast agent, WON and its margins were clearly identified as an avascular area and were punctured under CH-EUS guidance. CH-EUS enables the assessment of the microvasculature and hemodynamics of the target lesion in real time. It may also provide valuable information and could be a useful modality for EUS-TD to clearly visualize target lesions and their margins and to decisively puncture them, even when they could not be identified using B-mode EUS.

BACKGROUND AND AIMS: EUS-guided FNA (EUS-FNA) is used for the diagnosis of pancreatic adenocarcinoma, but sometimes the method results in a false negative. Occasionally, an avascular area may be observed within the pancreatic adenocarcinoma tumor during contrast-enhanced harmonic EUS (CH-EUS). The aim of this study was to evaluate whether the diagnostic sensitivity of EUS-FNA for pancreatic adenocarcinoma was affected by the presence of avascularity on CH-EUS. METHODS: Two hundred ninety-two patients with pancreatic adenocarcinoma who presented at Kindai University Hospital for EUS-FNA and CH-EUS between June 2009 and August 2013 were retrospectively evaluated. This was a single-center retrospective analysis of prospectively collected data held in a registry. The overall sensitivity of EUS-FNA for the diagnosis of pancreatic adenocarcinoma was calculated. The sensitivities of cytology, histology, and the combination of cytology and histology were also evaluated. These variables were individually evaluated according to the presence or absence of an avascular area on CH-EUS to assess whether the diagnostic sensitivity of EUS-FNA for pancreatic adenocarcinoma was related to the presence of an avascular area within the tumors. RESULTS: The overall sensitivity of EUS-FNA was 90.8% (265/292). The sensitivities of EUS-FNA for lesions with and without an avascular area were 72.9% (35/48) and 94.3% (230/244), respectively, with the difference being statistically significant (P < .001). CONCLUSIONS: EUS-FNA has lower sensitivity for pancreatic adenocarcinoma with avascular areas on CH-EUS.

BACKGROUND AND AIM: Differential diagnosis of localized gallbladder lesions is challenging. The aim of the present study was to evaluate the utility of contrast-enhanced harmonic endoscopic ultrasonography (CH-EUS) for diagnosis of localized gallbladder lesions. METHODS: One hundred and twenty-five patients with localized gallbladder lesions were evaluated by CH-EUS between March 2007 and February 2014. This was a single-center retrospective study. Utilities of fundamental B-mode EUS (FB-EUS) and CH-EUS in the differentiation of gallbladder lesions and sludge plug were initially compared. Thereafter, these two examinations were compared with respect to their accuracy in the diagnosis of malignant lesions. Five reviewers blinded to the clinicopathological results evaluated microcirculation patterns in the vascular and perfusion images. RESULTS: In the differentiation between gallbladder lesions and sludge plug, FB-EUS had a sensitivity, specificity, and accuracy of 82%, 100%, and 95%, respectively, whereas CH-EUS had a sensitivity, specificity, and accuracy of 100%, 99%, and 99%, respectively. FB-EUS-based diagnosis of carcinomas based on tumor size and/or shape had a sensitivity, specificity, and accuracy of 61-87%, 71-88%, and 74-86%, respectively. Additional information regarding irregular vessel patterns in the vascular image and/or heterogeneous enhancement in the perfusion image on CH-EUS increased the sensitivity, specificity, and accuracy for the diagnosis of carcinomas to 90%, 98%, and 96%, respectively. There was a significant difference between FB-EUS and CH-EUS in terms of carcinoma diagnosis. CONCLUSION: CH-EUS was useful for the evaluation of localized gallbladder lesions.

BACKGROUND: Treatment of unresectable malignant hilar biliary stricture (UMHBS) is challenging, especially after failure of repeated transpapillary endoscopic stenting. Endoscopic ultrasonography-guided intrahepatic biliary drainage (EUS-IBD) is a recent technique for intrahepatic biliary decompression, but indications for its use for complex hilar strictures have not been well studied. The aim of this study was to assess the feasibility and safety of EUS-IBD for UMHBS after failed transpapillary re-intervention. METHODS: Retrospective analysis of all consecutive patients with UMHBS of Bismuth II grade or higher who, between December 2008 and May 2016, underwent EUS-IBD after failed repeated transpapillary interventions. The technical success, clinical success, and complication rates were evaluated. Factors associated with clinical ineffectiveness of EUS-IBD were explored. RESULTS: A total of 30 patients (19 women, median age 66 years [range 52-87]) underwent EUS-IBD for UMHBS during the study period. Hilar biliary stricture morphology was classified as Bismuth II, III, or IV in 5, 13, and 12 patients, respectively. The median number of preceding endoscopic interventions was 4 (range 2-14). EUS-IBD was required because the following procedures failed: duodenal scope insertion (n = 4), accessing the papilla after duodenal stent insertion (n = 5), or achieving desired intrahepatic biliary drainage (n = 21). Technical success with EUS-IBD was achieved in 29 of 30 patients (96.7%) and clinical success was attained in 22 of these 29 (75.9%). Mild peritonitis occurred in three of 30 (10%) and was managed conservatively. Stent dysfunction occurred in 23.3% (7/30). There was no procedure-related mortality. On multivariable analysis, Bismuth IV stricture predicted clinical ineffectiveness (odds ratio = 12.7, 95% CI 1.18-135.4, P = 0.035). CONCLUSIONS: EUS-IBD may be a feasible and effective rescue alternative with few major complications after failed transpapillary endoscopic re-intervention in patients with UMHBS, particularly for Bismuth II or III strictures.

BACKGROUND AND AIM: The study aims to evaluate contrast-enhanced harmonic endoscopic ultrasonography (CH-EUS) for the differential diagnosis of submucosal tumors (SMT) of the upper gastrointestinal tract. METHODS: Between June 2008 and May 2015, 157 consecutive patients with submucosal lesions of the upper gastrointestinal tract were evaluated by CH-EUS. This was a single-center retrospective analysis of prospectively collected data in a registry. The data from 73 patients who later underwent surgical resection were analyzed in this study. Surgical specimens served as the final diagnoses. The two CH-EUS variables of blood flow (hyper-enhancement vs hypo-enhancement) and homogeneity of enhancement pattern were evaluated. RESULTS: The final diagnoses were 58 gastrointestinal stromal tumors (GISTs) and 15 benign SMTs (two lipomas, five leiomyomas, five schwannomas, two glomus tumors, and one ectopic pancreas). On CH-EUS, 49 of 58 (84.5%) GISTs presented with hyper-enhancement, whereas 4 of 15 (26.7%) benign SMTs showed hyper-enhancement; 21 of 58 (36.2%) GISTs showed inhomogeneous contrast enhancement, while only 2 of 15 (13.3%) benign SMTs demonstrated inhomogeneous contrast enhancement. If hyper-enhancement was considered to indicate GISTs, the sensitivity, specificity, and accuracy were 84.5%, 73.3%, and 82.2%, respectively. If inhomogeneous enhancement was considered to indicate GISTs, the sensitivity, specificity, and accuracy were 36.2%, 86.7%, and 46.6%, respectively. In lesions of less than 2 cm, hyper-enhancement was a more sensitive indicator of GISTs than inhomogeneous enhancement. CONCLUSIONS: Hyper-enhancement and inhomogeneous enhancement were found to be a characteristic of GISTs. CH-EUS was useful for discrimination of benign SMTs from GISTs.

EUS-guided hepaticogastrostomy (EUS-HGS) is useful for treating obstructive jaundice. However, stent migration may sometimes occur both during and after the procedure. This report describes a patient with pancreatic cancer and massive ascites who underwent EUS-HGS combined with EUS-guided antegrade stenting (EUS-AS), with additional EUS-AS playing a role in troubleshooting for stent migration during EUS-HGS.

BACKGROUND AND AIM: Endoscopic ultrasonography (EUS)-guided choledochoduodenostomy (EUS-CDS) is increasingly used in the treatment of malignant distal biliary obstruction. Standardized use of this technique requires improvements in instruments, including more convenient and safer devices. The present study was designed to evaluate the resistance force to migration (RFM) of a newly designed laser-cut metal stent and the feasibility of EUS-CDS using this stent. METHODS: This experimental study used a porcine model of biliary dilatation involving five male pigs. The new stent is a fully covered laser-cut stent with anti-migration anchoring hooks. The RFM of the new stents was compared with those of three commercially available covered metal stents using a phantom model. In the animal study, after ligation of Vater's ampulla with endoscopic clips, the dilated common bile duct was punctured under EUS guidance, followed by EUS-CDS using the new stent. One week after the procedure, the stents were removed endoscopically and the fistulas were assessed after the pigs were killed. Technical feasibility and clinical outcomes were evaluated. RESULTS: Among the four stents, the new stent had the highest RFM. Metal stent placement was successful in all five pigs, with no procedure-related complications occurring during and 1 week after endoscopic intervention. All stents remained in place without migration and were removed easily using a snare. At necropsy, fistulas were created between the bile duct and duodenum in all pigs. CONCLUSION: EUS-CDS using a newly designed metal stent was feasible and effective in this porcine model of biliary dilatation.

AIM: To assess the long-term outcomes of this procedure after removal of self-expandable metal stent (SEMS). The efficacy and safety of endoscopic ultrasound-guided gallbladder drainage (EUS-GBD) with SEMS were also assessed. METHODS: Between January 2010 and April 2015, 12 patients with acute calculous cholecystitis, who were deemed unsuitable for cholecystectomy, underwent EUS-GBD with a SEMS. EUS-GBD was performed under the guidance of EUS and fluoroscopy, by puncturing the gallbladder with a needle, inserting a guidewire, dilating the puncture hole, and placing a SEMS. The SEMS was removed and/or replaced with a 7-Fr plastic pigtail stent after cholecystitis improved. The technical and clinical success rates, adverse event rate, and recurrence rate were all measured. RESULTS: The rates of technical success, clinical success, and adverse events were 100%, 100%, and 0%, respectively. After cholecystitis improved, the SEMS was removed without replacement in eight patients, whereas it was replaced with a 7-Fr pigtail stent in four patients. Recurrence was seen in one patient (8.3%) who did not receive a replacement pigtail stent. The median follow-up period after EUS-GBD was 304 d (78-1492). CONCLUSION: EUS-GBD with a SEMS is a possible alternative treatment for acute cholecystitis. Long-term outcomes after removal of the SEMS were excellent. Removal of the SEMS at 4-wk after SEMS placement and improvement of symptoms might avoid migration of the stent and recurrence of cholecystitis due to food impaction.

OBJECTIVES: This study evaluated whether quantitative perfusion analysis with contrast-enhanced harmonic (CH) endoscopic ultrasonography (EUS) characterizes pancreatic tumors, and compared the hemodynamic parameters used to diagnose pancreatic carcinoma. METHODS: CH-EUS data from pancreatic tumors of 76 patients were retrospectively analyzed. Time-intensity curves (TIC) were generated to depict changes in signal intensity over time, and 6 parameters were assessed: baseline intensity, peak intensity, time to peak, intensity gain, intensity at 60 s (I60), and reduction rate. These parameters were compared between pancreatic carcinomas (n = 41), inflammatory pseudotumors (n = 14), pancreatic neuroendocrine tumors (n = 14), and other tumors (n = 7). All 6 TIC parameters and subjective analysis for diagnosing pancreatic carcinoma were compared. RESULTS: Values of peak intensity and I60 were significantly lower and time to peak was significantly longer in the groups with pancreatic carcinomas than in the other 3 tumor groups (p < 0.05). Reduction rate was significantly higher in pancreatic carcinomas than in pancreatic neuroendocrine tumors (p < 0.05). Areas under the receiver-operating characteristic curves for the diagnosis of pancreatic carcinoma using subjective analysis, baseline intensity, peak intensity, intensity gain, I60, time to peak, and reduction rate, were 0.817, 0.664, 0.810, 0.751, 0.845, 0.777, and 0.725, respectively. I60 was the most accurate parameter for differentiating pancreatic carcinomas from the other groups, giving values of sensitivity/specificity of 92.7/68.6% when optimal cutoffs were chosen. CONCLUSIONS: In pancreatic carcinomas, TIC patterns were markedly different from the other tumor types, with I60 being the most accurate diagnostic parameter. Quantitative perfusion analysis is useful for differentiating pancreatic carcinomas from other pancreatic tumors.

BACKGROUND: Endoscopic ultrasound (EUS)-guided biliary drainage (BD) is a well-recognized alternative BD method after unsuccessful endoscopic transpapillary drainage. EUS-guided hepaticogastrostomy (HGS) with antegrade stenting (AGS) was recently applied to the treatment of malignant obstructive jaundice. OBJECTIVE: To assess the efficacy and safety of HGS combined with AGS for treatment of malignant biliary stricture-induced obstructive jaundice. DESIGN: Retrospective cohort study. SETTING: Single academic tertiary care center. PATIENTS: From January 2006 to December 2014, endoscopic retrograde cholangiopancreatography was attempted in patients with obstructive jaundice; it was successful in 641 patients and impossible in 154 patients (postsurgically altered anatomy or duodenal stenosis, n = 101; difficult cannulation, n = 53). In total, 145 patients underwent EUS-guided BD; HGS and HGS with AGS were attempted in 42 patients (Group A, January 2006-August 2011) and 37 patients (Group B, September 2011-December 2014), respectively. INTERVENTIONS: Under EUS and fluoroscopy guidance, HGS and HGS with AGS were performed via needle puncture, guidewire insertion, puncture-hole dilation, and stent placement. MAIN OUTCOME MEASUREMENTS: Groups A and B were compared in terms of technical success, functional success, adverse event rates, re-intervention rates, patient survival time, and time to stent dysfunction or patient death. The two groups were also compared in a subgroup analysis of only 28 patients who underwent chemotherapy. RESULTS: The technical success rate was significantly higher in Group A than B (97.6 vs. 83.8%, p = 0.03). The functional success rate was comparable between the two groups (90.2 vs. 90.3%), although the rate of adverse events was significantly higher in Group A than B (26.1 vs. 10.8%, p = 0.03). The re-intervention rate tended to be higher in Group A than B (16.7 vs. 8.1%, p = 0.25). Groups A and B did not differ significantly in terms of median overall patient survival (75 vs. 61 days, p = 0.70) or median time to stent dysfunction or patient death (68 vs. 63 days, p = 0.08). Among patients who underwent chemotherapy, there was no difference in overall patient survival time between the two groups (121 vs. 157 days, p = 0.08), although time to stent dysfunction or patient death was significantly shorter in Group A than B (71 vs. 95 days, p = 0.02). CONCLUSION: Although the technical success rate of HGS with AGS was lower than that of HGS, HGS with AGS was superior to HGS in terms of adverse event rate and stent patency in patients receiving chemotherapy.

Repeated pancreatic juice cytology via endoscopic nasopancreatic drainage (ENPD) has a high diagnostic yield and might be useful for the diagnosis of early-stage pancreatic cancer. A 67-year-old man presented with a pancreatic cyst occasionally detectable in the body of the pancreas by ultrasonography (US). No obvious pancreatic tumor was detected by US, computed tomography (CT), magnetic resonance cholangiopancreatography, and endoscopic ultrasound (EUS) (although the latter did reveal a weak, low echoic area). Endoscopic retrograde pancreatography showed irregular narrowing of the main pancreatic duct (MPD) at the pancreatic body. Pancreatic juice cytology was also performed, but did not give evidence of a malignancy. Therefore, the patient was followed up. CT and EUS performed after 3 months showed the same findings as did endoscopic retrograde pancreatography; however, the results of repeated pancreatic juice cytology performed via ENPD tube revealed a suspected malignancy on 2 of 6 occasions. Therefore, we performed a central pancreatectomy. Histopathological examination of a resected specimen revealed carcinoma in situ in the narrow MPD at the body of the pancreas. In the current case, repeated pancreatic juice cytology via ENPD was effective. A weak low echoic area around the MPD stricture on EUS might be related to the inflammatory change accompanying carcinoma in situ of the pancreas.

BACKGROUND AND AIMS: Risk factors for pancreatic ductal adenocarcinoma (PDAC) include diabetes mellitus, chronic pancreatitis, obesity, a family history of pancreatic cancer, and a history of smoking or alcohol consumption. The aim of this study was to evaluate the association between risk factors for PDAC and malignant intraductal papillary mucinous neoplasm (IPMN). METHODS: The study included 134 consecutive patients with IPMN who underwent surgical resection at Kindai University Hospital between April 2009 and March 2015. Data on the presence or absence of mural nodules (MNs) and risk factors for PDAC were evaluated. Multivariable logistic regression analysis was performed with malignant IPMN as the outcome variable and MNs and risk factors for PDAC as explanatory variables. RESULTS: The odds ratio of malignant IPMN to MNs was 3.88 (95% confidence interval [CI] 1.53-9.84; p = 0.004), whereas that of malignant IPMN to smoking history was 1.66 (95% CI 0.74-3.71; p = 0.22). When the presence of MNs was considered as a predictive factor for malignancy, the sensitivity and specificity were 88.5 and 32.1%, respectively, whereas when the presence of both smoking history and MNs was considered, the specificity improved to 73.2%, with a decrease in sensitivity to 42.3%. CONCLUSIONS: The presence of both a smoking history and MNs was a valuable predictive factor for malignant IPMN with high specificity. A smoking history should be considered before surgical resection in addition to the presence of MNs.

AIM: To assess anti-migration potential of six biliary covered self-expandable metal stents (C-SEMSs) by using a newly designed phantom model. METHODS: In the phantom model, the stent was placed in differently sized holes in a silicone wall and retracted with a retraction robot. Resistance force to migration (RFM) was measured by a force gauge on the stent end. Radial force (RF) was measured with a RF measurement machine. Measured flare structure variables were the outer diameter, height, and taper angle of the flare (ODF, HF, and TAF, respectively). Correlations between RFM and RF or flare variables were analyzed using a linear correlated model. RESULTS: Out of the six stents, five stents were braided, the other was laser-cut. The RF and RFM of each stent were expressed as the average of five replicate measurements. For all six stents, RFM and RF decreased as the hole diameter increased. For all six stents, RFM and RF correlated strongly when the stent had not fully expanded. This correlation was not observed in the five braided stents excluding the laser cut stent. For all six stents, there was a strong correlation between RFM and TAF when the stent fully expanded. For the five braided stents, RFM after full stent expansion correlated strongly with all three stent flare structure variables (ODF, HF, and TAF). The laser-cut C-SEMS had higher RFMs than the braided C-SEMSs regardless of expansion state. CONCLUSION: RF was an important anti-migration property when the C-SEMS did not fully expand. Once fully expanded, stent flare structure variables plays an important role in anti-migration.

BACKGROUND AND AIMS: EUS-guided bile duct drainage (EUS-BD) is a well-recognized rescue biliary drainage method after unsuccessful ERCP. EUS-guided gallbladder drainage (EUS-GBD) was recently used to treat acute cholecystitis. The aim of this study was to assess the efficacy and safety of EUS-GBD for malignant biliary stricture-induced obstructive jaundice after unsuccessful ERCP as well as unsuccessful or impractical EUS-BD. METHODS: Between January 2006 and October 2014, 12 patients with obstructive jaundice due to unresectable malignant distal biliary stricture underwent EUS-GBD after ERCP failed. EUS-GBD was performed under the guidance of EUS and fluoroscopy by puncturing the gallbladder with a needle, inserting a guidewire, dilating the puncture hole, and placing a stent. The technical and functional success rates, adverse events rate, overall patient survival time, and stent dysfunction rate during patient survival were measured. RESULTS: The rates of technical success, functional success, adverse events, and stent dysfunction were 100%, 91.7%, 16.7%, and 8.3%, respectively. The median survival time after EUS-GBD was 105 days (range 15 - 236 days). CONCLUSIONS: EUS-GBD is a possible alternative route for decompression of the biliary system when ERCP is unsuccessful.

Endoscopic ultrasonography (EUS) is widely used to evaluate pancreaticobiliary diseases, especially pancreatic masses. EUS has a good ability to detect pancreatic masses, but it is not sufficient for the differential diagnosis of various types of lesions. In order to address the limitations of EUS, new techniques have been developed to improve the characterization of the lesions detected by EUS. EUS-guided fine needle aspiration (EUS-FNA) has been used for diagnosing pancreatic tumors. In order to improve the histological diagnostic yield, a EUS-FNA needle with a core trap has recently been developed. Contrast-enhanced harmonic EUS is a new imaging modality that uses an ultrasonographic contrast agent to visualize blood flow in fine vessels. This technique is useful in the diagnosis of pancreatic solid lesions and in confirming the presence of vascularity in mural nodules for cystic lesions. EUS elastography analyzes several different variables to measure tissue elasticity, color patterns, and strain ratio, using analytical techniques such as hue-histogram analysis, and artificial neural networks, which are useful for the diagnosis of chronic pancreatitis and pancreatic cancer.

BACKGROUND: Interventional endoscopic ultrasound (EUS)-guided procedures such as EUS-guided celiac ganglia neurolysis (EUS-CGN) and EUS-guided broad plexus neurolysis (EUS-BPN) were developed to treat abdominal cancer-associated pain; however, these procedures are not always effective. The aim of this study was to explore predictors of pain response in EUS-guided neurolysis for pancreatic cancer-associated pain. METHODS: This was a retrospective analysis of prospectively collected data of 112 consecutive patients who underwent EUS-BPN in our institution. EUS-CGN was added in cases of visible celiac ganglia. The neurolytic-spread area was divided into six sections and evaluated by post-procedural computed tomography scanning. Pain intensity was assessed using a visual analog scale (VAS), and a decrease in VAS scores by ⩾3 points after neurolysis was considered a good pain response. Univariable and multivariable logistic regression analyses were performed to explore predictors of pain response at 1 and 4 weeks, and complications. RESULTS: A good pain response was obtained in 77.7% and 67.9% of patients at 1 and 4 weeks, respectively. In the multivariable analysis of these patients, the combination method (EUS-BPN plus CGN) was a significant positive predictive factor at 1 week (odds ratio = 3.69, p = 0.017) and 4 weeks (odds ratio = 6.37, p = 0.043). The numbers of neurolytic/contrast spread areas (mean ± SD) were 4.98 ± 1.08 and 4.15 ± 1.12 in patients treated with the combination method and single method, respectively (p < 0.001). There was no significant predictor of complications. CONCLUSIONS: EUS-BPN in combination with EUS-CGN was a predictor of a good pain response in EUS-guided neurolysis for pancreatic cancer-related pain. The larger number of neurolytic/contrast spread areas may lead to better outcomes in patients receiving combination treatment.

We report a successful endoscopic ultrasonography-guided drainage of a huge infected multilocular walled-off necrosis (WON) that was treated by a modified single transluminal gateway transcystic multiple drainage (SGTMD) technique. After placing a wide-caliber fully covered metal stent, follow-up computed tomography revealed an undrained subcavity of WON. A large fistula that was created by the wide-caliber metal stent enabled the insertion of a forward-viewing upper endoscope directly into the main cavity, and the narrow connection route within the main cavity to the subcavity was identified with a direct view, leading to the successful drainage of the subcavity. This modified SGTMD technique appears to be useful for seeking connection routes between subcavities of WON in some cases.

Acute obstructive suppurative cholangitis (AOSC) due to biliary lithiasis is a life-threatening condition that requires urgent biliary decompression. Although endoscopic retrograde cholangiopancreatography (ERCP) with stent placement is the current gold standard for biliary decompression, it can sometimes be difficult because of failed biliary cannulation. In this retrospective case series, we describe three cases of successful biliary drainage with recovery from septic shock after urgent endoscopic ultrasound-guided choledochoduodenostomy (EUS-CDS) was performed for AOSC due to biliary lithiasis. In all three cases, technical success in inserting the stents was achieved and the patients completely recovered from AOSC with sepsis in a few days after EUS-CDS. There were no procedure-related complications. When initial ERCP fails, EUS-CDS can be an effective life-saving endoscopic biliary decompression procedure that shortens the procedure time and prevents post-ERCP pancreatitis, particularly in patients with AOSC-induced sepsis.

AIM: To assess the usefulness of contrast-enhanced harmonic endoscopic ultrasonography (CH-EUS) for lymph node metastasis in pancreatobiliary carcinoma. METHODS: All patients suspected of pancreatobiliary carcinoma with visible lymph nodes after standard EUS between June, 2009 and January, 2012 were enrolled. In the primary analysis, patients with successful EUS-fine needle aspiration (FNA) were included. The lymph nodes were assessed by several standard EUS variables (short and long axis lengths, shape, edge characteristic and echogenicity), color Doppler EUS variable [central intranodal blood vessel (CIV) presence] and CH-EUS variable (heterogeneous/homogeneous enhancement patterns). The diagnostic accuracy relative to EUS-FNA was calculated. In the second analysis, N-stage diagnostic accuracy of CH-EUS was compared with EUS-FNA in patients who underwent surgical resection. RESULTS: One hundred and nine patients (143 lymph nodes) fulfilled the criteria. The short axis cut-off ≥ 13 mm predicted malignancy with a sensitivity and specificity of 72% and 85%, respectively. These values were 72% and 63% for the long axis cut-off ≥ 20 mm, 62% and 75% for the round shape variable, 81% and 30% for the sharp edge variable, 66% and 61% for the hypoechogenicity variable, 70% and 72% for the CIV-absent variable, and 83% and 91% for the heterogeneous CH-EUS-enhancement variable, respectively. CH-EUS was more accurate than standard and color Doppler EUS, except the short axis cut-off. Notably, three patients excluded because of EUS-FNA failure were correctly N-staged by CH-EUS. CONCLUSION: CH-EUS complements standard and color Doppler EUS and EUS-FNA for assessment of lymph node metastases.

BACKGROUND AND STUDY AIM: Comparison of fundamental B-mode endoscopic ultrasonography (FB-EUS) and contrast-enhanced harmonic endoscopic ultrasonography (CH-EUS) in the differential diagnosis of pancreatic cysts according to presence of mural nodules. PATIENTS AND METHODS: Between April 2007 and April 2012, FB-EUS and CH-EUS data were prospectively collected from 581 consecutive patients with pancreatic cysts, and were retrospectively analyzed from 70 with subsequent cyst resection. Presence and height of mural nodules as detected on FB-EUS and CH-EUS were evaluated, and thence accuracies of both methods for diagnosing mucinous versus nonmucinous and malignant versus benign cysts. RESULTS: On pathological examination 48 cysts were mucinous and 22 were nonmucinous; 30 cysts were malignant (high grade dysplasia or invasive carcinoma) and 40 were benign. If presence of a mural nodule was considered to indicate a mucinous cyst, FB-EUS and CH-EUS accuracies did not differ significantly (respectively: sensitivity 85 % vs. 79 %; specificity 46 % vs. 96 %; accuracy 73 % vs. 84 %, P = 0.057). If presence of mural nodule was considered to indicate malignancy, CH-EUS was significantly more accurate than FB-EUS (respectively: sensitivity 97 % vs. 97 %; specificity 75 % vs. 40 %; accuracy 84 % vs. 64 %, P = 0.0001). For diagnosing malignancy by evaluating mural nodule height, the area under the receiver operating characteristic (AUROC) was 0.84 and 0.93 for FB-EUS and CH-EUS, respectively (P = 0.028). Presence of a mural nodule of height ≥ 4 mm on CH-EUS was a sign of malignancy (false-positive fraction 0.2; true-positive fraction 0.93; odds ratio 56.0). CONCLUSIONS: CH-EUS is more accurate than FB-EUS for diagnosing malignant pancreatic cysts.

第二世代の超音波造影剤であるソナゾイドを用いた膵腫瘍性病変における造影US(CEUS)の有用性が報告されている。超音波内視鏡などの登場により、その位置付けが変化しつつあるものの、CEUSは血流評価のリアルタイム性、肝転移の検索、幅広い適応という点で現在の環境においても非常に有用な診断ツールである。各疾患別の比較においては、浸潤性膵管癌の多くはhypo-enhancementされかつゆっくりと造影されるのが典型的であり、腫瘤形成性膵炎は、iso-enhancementされることが多い。腫瘤形成性膵炎でもhypo-enhancementされる症例が存在し、浸潤性膵管癌との鑑別を要する。膵神経内分泌腫瘍に関しては、hyper-enhancementされることが多いが、Ki67の値によっては例外もある。造影パターンとKi67の相関も報告されており、症例の蓄積が期待される。CEUSは、膵腫瘍患者にとって最適な診断ツールであり、ソナゾイドの使用が保険収載され、汎用化されると、診断能の向上に寄与することが期待される。(著者抄録)

急性胆嚢炎に対するドレナージ治療として、EUS下穿刺術を応用したEUS下胆嚢ドレナージ術(EUS-GBD)が報告されている。EUS観察下で胃前庭部または十二指腸球部より腫大した胆嚢を穿刺する。穿刺後、生理食塩水にて胆嚢内を洗浄した上で、胆嚢内にガイドワイヤーをコイリングする要領で留置し、続いて穿刺孔を拡張する。最後に経鼻ドレナージチューブ、両端ピッグテイルステントあるいは金属ステントを留置する。新しい手技のため、報告が少ないが、手技成功率97〜100%、臨床症状改善率100%と良好な成績が得られている。主な偶発症として、胆汁性腹膜炎気腹症、ステントの迷入、逸脱がある。今後、EUS-GBDは経皮経肝胆嚢ドレナージ術、経皮経肝胆嚢吸引穿刺法、内視鏡的経鼻胆嚢ドレナージ術、内視鏡的胆嚢ステント留置術と同様、急性胆嚢炎に対する治療選択肢となりうる。(著者抄録)

内視鏡的に逆流性食道炎(RE)と診断され、プロトンポンプ阻害薬(PPI)を継続投与している57例において、GerdQを用いて治療効果の評価および背景因子との関係を検討した。PPI用量は常用量使用例が75.4%と半量使用例よりも多く、また87.7%がPPI単独使用であり、その他の消化器治療薬との併用例は少なかった。食道炎の重症度はLA gradeN例が56.1%と最も多く、gradeCあるいはDは認めなかった。11例がPPIの治療効果不十分と判定された。PPI継続治療後の直近のLA grade別では、gradeの高い症例で効果不十分例を有意に多く認めた。効果十分例についてはgradeNおよびMが69.6%および8.7%、gradeA以上は21.7%であった。また、食道裂孔ヘルニアの有無では、食道裂孔ヘルニアを有する患者で効果不十分例を多く認めた。