橋本 千樹

Gallbladder (GB) diseases represent various lesions including gallstones, cholesterol polyps, adenomyomatosis, and GB carcinoma. This review aims to summarize the role of endoscopic ultrasound (EUS) in the diagnosis of GB lesions. EUS provides high-resolution images that can improve the diagnosis of GB polypoid lesions, GB wall thickness, and GB carcinoma staging. Contrast-enhancing agents may be useful for the differential diagnosis of GB lesions, but the evidence of their effectiveness is still limited. Thus, further studies are required in this area to establish its usefulness. EUS combined with fine-needle aspiration has played an increasing role in providing a histological diagnosis of GB tumors in addition to GB wall thickness.

＜文献概要＞経腹壁超音波検査(TUS)は簡便に施行可能で,低侵襲的な画像検査のため,胆管癌を診断するスクリーニング検査として位置づけられている.消化管ガスなどの被検者の要因によっては,胆管主病変を直接描出することが困難なことがあるが,肝内外胆管の拡張など間接所見にも注意する必要がある.超音波内視鏡検査(EUS)は,精密検査として施行され,胆管癌の質的診断や局所進展度診断に有用性が高い.EUS-FNAは,needle tract seedingのリスクが高いため,切除可能胆管癌患者では避ける必要がある.TUS,EUSは,術者の技能によって診断能に大きな違いが生じるため,検査に携わる者は,より正確に診断を行えるよう,超音波検査手技,臨床解剖,疾患について熟知しておくことが重要である.

OBJECTIVES: There are few reports on the long-term prognosis of papillary tumors after endoscopic papillectomy. Here, we report a retrospective study of the therapeutic effects, long-term prognosis, and affecting factors. METHODS: The inclusion criteria were papillary adenoma with/without an adenocarcinoma component on biopsy results and ≤10 mm intraductal extension, and the exclusion criteria were moderate to poorly differentiated adenocarcinoma on biopsy results. If no residual lesion was confirmed ≥6 months after the last endoscopic treatment, remission was defined. Subsequently, follow-up endoscopy was scheduled once a year. Surgery was required in the case of adenocarcinoma recurrence or intraductal lesions >10 mm. The rates of adverse events, remission, recurrence, and need for surgery were examined. The affecting factors were calculated. RESULTS: There were a total of 253 subjects, including 65 with adenocarcinoma. Pancreatitis (7.5%), bleeding (9.1%) and perforation (2.8%) were observed as adverse events. Among 221 subjects with ≥6 months of follow-up, 212 (95.9%) were in remission. The cumulative recurrence rate using the Kaplan-Meier analysis at 5 years was 16.9% (22 cases), with the need for surgery in 5.9% (5 cases). Intraductal extension on preoperative diagnosis was the only significant risk factor for both recurrence (P < 0.001) and the need for surgery (P = 0.005). The presence of adenocarcinoma had no significant effect. CONCLUSION: Although remission was achieved in more than 95% of our patients, we observed a high rate of recurrence at the long-term follow-up, which was significantly associated with intraductal extension but not with the presence of adenocarcinoma.

Background and Aim: This study investigated the efficacy of transcatheter arterial infusion (TAI) chemotherapy with cisplatin combined with transcatheter arterial chemoembolization (TACE). The goal was to prevent intrahepatic distant recurrence (IDR) of hepatocellular carcinoma (HCC), compared with TACE alone, in patients with unresectable HCC. Methods: We conducted a historical cohort study, which involved 68 unresectable HCC patients. The study was performed on 44 and 24 consecutive patients who underwent TAI using cisplatin combined with TACE using epirubicin and TACE using epirubicin alone, respectively. We performed a propensity score analysis to identify the independent risk factors associated with IDR, and constructed propensity score-adjusted survival curves. Results: After propensity score-adjusting, the adjusted cumulative IDR rates at 1 and 3 years were 76.8 and 76.8% in TACE alone group, and 21.3 and 73.1% in TACE with TAI group, respectively. TACE alone group had a significantly higher IDR rate in comparison with TACE with TAI group (P = 0.0073). Combined with TAI was associated with preventing IDR after propensity score-adjusting (hazard ratio [HR] 0.40, 95% confidence intervals [CI] 0.17-0.91, P = 0.028). Combined with TAI (HR 0.26, 95% CI 0.10-0.68, P = 0.0056) and Stage ≥III (HR 2.98, 95% CI 1.25-7.12, P = 0.014) were independent IDR predictors after adjusting for significant risk factors with propensity score. Conclusions: We demonstrated that cisplatin TAI accompanied with TACE decreased IDR compared with TACE alone. Our findings suggest that cisplatin TAI might contribute to a longer progression-free period in unresectable HCC patients treated with TACE.

BACKGROUND: Endoscopic papillectomy of duodenal papillary tumors (PT) is indicated for adenomas or well-differentiated adenocarcinomas that do not involve the sphincter of Oddi. However, there is currently no reliable pre-operative method to diagnose the infiltration in the sphincter of Oddi.' Insulin-like growth factor 2 mRNA protein 3 (IMP3) staining is reportedly associated with advanced disease stage and clinical outcomes in many carcinomas. The aim of this retrospective study was to investigate the ability of diagnosing sphincter of Oddi involvement in PT and predicting the prognoses using IMP3 immunohistochemistry. METHODS: Twenty-five resected specimens from patients with PT and 24 biopsy specimens from the same patients excluding one were immunostained for IMP3. The percentage of positive cells in the tumor was evaluated and compared with the final pathological diagnosis and prognosis. RESULTS: The final pathological diagnoses were adenoma in 5 patients and adenocarcinoma in 20 patients (no sphincter of Oddi involvement in 5 and involvement in 15). The ability to diagnose sphincter of Oddi involvement based on the percentage of IMP3-positive cells in resected specimens and tissue biopsies was the area under the curve 0.8 and 0.78, respectively, of the receiver operating characteristic curve, and the accuracies were 80.0% and 75.0% (cutoff value: 10%), respectively. Moreover, patients with an IMP3-positive cell rate of ≥ 10% had a significantly worse prognosis (log-rank test P = 0.01). CONCLUSION: IMP3 immunostaining of resected and biopsy specimens from PT patients enables the diagnosis of sphincter of Oddi involvement objectively and is also effective in predicting the prognosis.

世界ではじめて早期慢性膵炎を取り入れた診断基準「慢性膵炎臨床診断基準2009」が本邦から提唱されてから10年間が経過した。この間、慢性膵炎の病態形成メカニズムに着目したmechanistic definitionとよばれる概念が海外から提唱され、早期慢性膵炎もこの定義に取り入れられた。この概念から考えると、早期慢性膵炎は機能不全に至っておらずまた可逆性の病態を想定している。2019年日本で発表された、慢性膵炎の新基準「慢性膵炎臨床診断基準2019」もこの概念を取り入れ、早期慢性膵炎の診断項目は危険因子の観点から改訂された。現在、早期慢性膵炎は国際的にその概念が確立されつつあるが、いまだ確立された定義や診断基準はなく、画像診断のみならず、遺伝や環境因子、その他さまざまなバイオマーカーを踏まえ、鑑別診断を明確に否定し適切に診断することで、慢性膵炎の進行を防ぎ後期合併症を回避することが重要である。今後新たなバイオマーカーや診断方法の開発が期待される。(著者抄録)

BACKGROUND/AIM: The aim of this study was to investigate the outcomes of atezolizumab plus bevacizumab in patients with advanced hepatocellular carcinoma (HCC), including those with disease refractory to lenvatinib, in clinical practice. PATIENTS AND METHODS: Of 34 patients treated with atezolizumab plus bevacizumab, a total of 23, including 16 with lenvatinib failure, were enrolled in this retrospective study. The adverse events, changes in liver function and antitumor responses at 6 weeks after starting therapy were evaluated. RESULTS: The incidence of grade 3 adverse events was low, at 13.0%. Albumin-bilirubin scores did not worsen at 3 and 6 weeks compared to baseline. The objective response rate and disease control rate at 6 weeks were 17.4% and 78.3% according to Response Evaluation Criteria in Solid Tumors (RECIST), and 30.4% and 78.3% according to modified RECIST, respectively. CONCLUSION: Our results suggest that atezolizumab plus bevacizumab might have potential therapeutic safety and efficacy in patients with advanced HCC, including those with disease refractory to lenvatinib. Further studies are needed to confirm the outcomes of atezolizumab plus bevacizumab after lenvatinib failure.

BACKGROUND AND AIM: The image-based diagnosis of pancreatic diseases can be difficult and requires pathological evaluation. Probe-based confocal laser endomicroscopy (pCLE) enables real-time observation of the microscopic tissue pattern of lesion and may be a useful assistance for the diagnosis. This study aimed to evaluate the feasibility and utility of pCLE for the diagnosis of pancreatic diseases. METHODS: Thirty patients who underwent endoscopic retrograde cholangiopancreatography with pCLE for the evaluation of indeterminate pancreatic diseases from June 2015 to October 2018 were included in this study. The pCLE findings were interpreted according to the Miami Classification. RESULTS: Among a total of 30 patients, 12, 10, 4, and 4 patients received the definitive diagnoses of pancreatic ductal adenocarcinoma (PDAC), main duct intrapapillary mucinous neoplasm, autoimmune pancreatitis, and chronic pancreatitis, respectively. The diagnostic accuracy of pCLE for PDAC and pancreatitis (96.7% and 93.3%, respectively) was higher than that of cytology (76.7% and 63.3%, respectively) (P = 0.0227 and 0.0048, respectively). The sensitivity of pCLE for PDAC was significantly higher (91.7%) than that of cytology (41.7%) (P = 0.0094). Moreover, the specificity of pCLE for pancreatitis was significantly higher than that of cytology (90.9% vs 50%; P = 0.0029). However, the diagnostic accuracies of pCLE and cytology for main duct intrapapillary mucinous neoplasm did not differ significantly (96.7% and 86.7%, respectively). CONCLUSIONS: Probe-based confocal laser endomicroscopy may be effective for the diagnosis of pancreatic diseases as adjunct modality. It requires technical learning and further evaluation of its usefulness.

重複胆管、重複胆嚢ともにまれな形態異常である。重複胆管は「2本のpatencyの保たれた胆管が別々に消化管に開口(double drainage)している先天奇形」と定義される。形態分類では斎藤らの分類を用いることが多い。また、重複胆嚢とは発育異常により胆嚢が2個あるいは3個ある先天異常のことを指す。Grossの分類により6型に分類する。重複胆管、重複胆嚢ともに、結石や胆道感染、胆道腫瘍の発症で外科的治療を要することがあり、その際には奇形である本症の解剖を十分理解し診療に臨む必要がある。(著者抄録)

PURPOSE: Shear wave elastography (SWE) using transabdominal ultrasonography (US) is widely used for diagnosis of tissue stiffness. Ultrasound shear wave dispersion (SWD) enables evaluation of tissue viscosity using SWE. The objective of this study was to investigate the reliability and clinical significance of SWD in pancreatic screening. METHODS: SWE and SWD were measured in 76 patients examined by US in pancreatic screenings performed between November 2017 and November 2018. The median pancreatic elastic modulus (PEM) and dispersion slope were obtained from at least five measurements. The reproducibility of these values and their correlations with patient characteristics, pancreatic echogenicity, and the pancreas-to-spleen attenuation ratio (P/S) on plain CT, which is associated with fatty change in pancreatic parenchyma, were investigated retrospectively. RESULTS: The median PEM and dispersion slope were 7.4 kPa and 15.7 (m/sec)/kHz, respectively, and both values had high intraclass correlation coefficients, showing high reproducibility (ρ = 0.869 and ρ = 0.867, respectively). The interquartile range/median value of PEM and dispersion slope were 0.36 and 0.28, respectively. PEM had a positive correlation with age (rs = 0.348, p = 0.002), and dispersion slope was positively correlated with age (rs = 0.278, p = 0.016) and BMI (rs = 0.397, p < 0.001). The hyperechoic pancreas had significantly higher PEM (6.6 vs. 7.8 kPa, p = 0.037) and dispersion slope (13.2 vs. 16.3 (m/sec)/kHz, p < 0.001). On plain CT performed in 50 patients, the P/S was not correlated with PEM (rs = - 0.180, p = 0.221), but was inversely correlated with dispersion slope (rs = - 0.338, p = 0.019). CONCLUSION: Measurement of SWD in pancreatic screening was highly reproducible and may permit objective evaluation of fatty change of the pancreas.

EUSによる胆嚢癌壁深達度診断は、主に壁層構造が何を表しているかの検討から始められた。現在のコンセンサスでは、胆嚢壁層構造が3層(内腔側から高・低・高エコー)の場合では、高エコー部分は境界エコーと粘膜(M)、低エコー部分は固有筋層(MP)と漿膜下層(SS)、最外層高エコー層は漿膜(S)とされている。2層構造の場合には、第1層低エコー層にM、MP、SSのどれもが含まれ得る。ただし、最外層高エコー層に変化がない場合には高度なSS浸潤はないと考えられている。現状においてEUSで確実に診断できることは、有茎性腫瘍(深達度M)の診断およびSS浸潤癌量の多寡といえる。(著者抄録)

現在、アレルギー性鼻炎、喘息、アトピー性皮膚炎、食物アレルギーといったなんらかのアレルギー疾患に罹患している人々は、急速に増加し、もはや国民の「2人に1人はアレルギー症状をもつ」状態まで増加している。この状況は、もはや国民的課題といっても過言ではなく、アレルギー症状の発症予防・改善にむけた検討を開始することは研究者として急務の課題であろう。この問題に対応するため、免疫学的・皮膚科学的観点から、減感作療法、薬物療法、スキンケアなど、取り組みが行われている。例えば、アレルギー疾患の一つであるアトピー性皮膚炎の発症予防や改善には一定の効果が報告されている。一方、食物アレルギーや花粉症などに代表される他のアレルギー疾患の有症率は急激な増加を示しており、この現状に鑑みると、個々人がセルフメディケーション的な観点で対応していくことが必要な時代になりつつあると感じる。つまり、個々人により、日常的に継続摂取可能且つ安全性が高く、明確なエビデンスを有する素材を摂取しながら、これらの予防・改善を目指すことが必要であろう。近年、様々な研究において、アレルギーと腸内マイクロバイオータ(=細菌叢全体を指す)の関係性を示す数々の報告がなされている。妊婦・乳幼児期の腸内マイクロバイオータがその後のアレルギーの発症に関し大きく影響を与えることを示した論文は多い。本稿では、妊婦・乳幼児の腸内マイクロバイオータとアレルギーとの関係性」を示しつつ、腸内マイクロバイオータのバランスの不均衡(=ディスバイオシス、Dysbiosis)を改善する素材である「プロバイオティクス/プレバイオティクスを用いたアレルギーの予防・改善」に関し、多角的な研究報告を紹介する。(著者抄録)

Pancreatic cystic lesions (PCLs) are incidental findings that are being increasingly identified because of recent advancements in abdominal imaging technologies. PCLs include different entities, with each of them having a peculiar biological behavior, and they range from benign to premalignant or malignant neoplasms. Therefore, accurate diagnosis is important to determine the best treatment strategy. As transabdominal ultrasonography (US) is noninvasive, inexpensive, and widely available, it is considered to be the most appropriate imaging modality for the initial evaluation of abdominal diseases, including PCLs, and for follow-up assessment. We present a review of the possibilities and limits of US in the diagnosis of PCLs, the technical development of US, and the ultrasonographic characteristics of PCLs.