橋本 千樹

The new Kyoto guidelines for the management of intraductal papillary mucinous neoplasm (IPMN) provide evidence-based recommendations for the diagnosis and treatment of IPMN. Endoscopic ultrasonography (EUS) is a diagnostic modality with a high spatial resolution that allows detailed observation and obtaining cyst fluid or tissue samples via EUS-guided fine needle aspiration (EUS-FNA). Currently, EUS is an indispensable examination method for the diagnosis of pancreatic diseases. On the other hand, there have been concerns that EUS imaging tends to be highly operator-dependent, and may lack objectivity. Previous guidelines have assigned EUS as an option for patients with worrisome features. However, recent reports indicate that the sensitivity of EUS for the diagnosis of mural nodules (MNs) is more than 90%, comparable or superior to that of contrast-enhanced computed tomography or magnetic resonance cholangiopancreatography. The specific advantages of EUS in the diagnosis of IPMN are: (1) high spatial resolution imaging for the diagnosis of MNs, (2) contrast-enhanced EUS for differentiation of intra-cystic MNs from mucous clots, and (3) pathological diagnosis using EUS-FNA and differential diagnosis of a pancreatic cystic tumor by cystic fluid analysis. In order to utilize EUS in the diagnosis of IPMN, endoscopists are required to have the skills to provide sufficiently objective imaging findings.

Less than half of all patients diagnosed with pancreatic ductal adenocarcinoma (PDAC) respond to chemotherapy, and the prognosis of PDAC is poor, which may be mediated by the gut microbiota. We investigated the clinical improvement effects of 1-kestose, a fructooligosaccharide, on PDAC chemotherapy in this single-center, randomized, controlled pilot trial conducted at Fujita Health University Hospital, which enrolled patients with PDAC. The trial included 1-kestose administration and non-administration groups. The 1-kestose group received 9 g of 1-kestose daily for 12 weeks, and their blood markers, imaging studies, physical findings, and gut microbiota were evaluated. In the 1-kestose administration group, the cancer marker CA19-9 significantly decreased, and there was a reduction in the neutrophil-to-lymphocyte ratio (NLR). There was also suppression of the reduction of albumin levels and of an increase in C-reactive protein. Additionally, Escherichia coli, which typically increases in PDAC, significantly decreased in the 1-kestose group. Thus, 1-kestose altered the gut microbiota and improved the prognostic factors for PDAC. Large-scale, long-term trials of 1-kestose interventions for PDAC are thus warranted to improve the prognosis of PDAC.

Endoscopic ultrasonography (EUS) provides high spatial resolution and more detailed images than other diagnostic modalities. Furthermore, EUS-guided tissue acquisition (EUS-TA), such as EUS-guided fine needle aspiration or biopsy (EUS-FNA/FNB), is an indispensable tool in pancreaticobiliary disease diagnostics, supporting a conclusive pathological diagnosis. In this review, we evaluate the current status and the usefulness of EUS-TA for the diagnostics of the following biliary tract diseases: (A) biliary stricture diagnostics, (B) biliary tract cancer (BTC) itself, and (C) staging of advanced BTC. Previous reports have shown that EUS-FNA for biliary lesions is a safe procedure that is useful in differentiating biliary cancer from benign lesions and in the staging of BTC. On the other hand, the diagnostic performance of EUS-TA for bile duct lesions is reported to be similar to that of transpapillary biopsy. Overall, EUS-TA for biliary lesions may be a safe and effective method, but it should be performed with an understanding of the risk of serious adverse events such as bile leakage and peritoneal dissemination of cancer. It is recommended for distal biliary stricture lesions for which endoscopic retrograde cholangiopancreatography cannot confirm the diagnosis or gallbladder lesions if they do not require the needle to pass through the biliary lumen.

膵腫瘍には様々な種類が存在し,予後と治療法は異なる.そのため,最善の治療計画を決定するには正確な診断が重要である.経腹的超音波検査は,膵腫瘍の画像診断のためのスクリーニング検査としてよく用いられる.本論説では,比較的稀な膵腫瘍の超音波所見の特徴に焦点を当てて解説する.(著者抄録)

Endoscopic ultrasonography (EUS) provides high spatial and contrast resolution and is a useful tool for evaluating the pancreato-biliary regions. Recently, contrast-enhanced harmonic EUS (CH-EUS) has been used to evaluate lesion vascularity, especially for the diagnosis of pancreatic tumors. CH-EUS adds two major advantages when diagnosing pancreatic cystic lesions (PCL). First, it can differentiate between mural nodules and mucous clots, thereby improving the accurate classification of PCL. Second, it helps with evaluation of the malignant potential of PCL, especially of intraductal papillary mucinous neoplasms by revealing the vascularity in the mural nodules and solid components. This review discusses the use and limitations of CH-EUS for the diagnosis of PCL.

BACKGROUND/AIM: The combination of atezolizumab plus bevacizumab (Atz/Bev) has become widely used as a first-line therapy for advanced hepatocellular carcinoma (HCC). However, for post-Atz/Bev therapy, evidence on the outcomes of molecular targeted agents, such as lenvatinib, is limited. The present study aimed to assess the clinical effectiveness of lenvatinib on advanced HCC in patients who had previously undergone Atz/Bev treatment. PATIENTS AND METHODS: Twenty patients with HCC, who received lenvatinib after Atz/Bev treatment, were enrolled in the study. In particular, we examined the impact of adverse events (AEs), such as anorexia and general fatigue. During the treatment, lenvatinib dosages were adjusted or temporarily discontinued in response to AEs. Treatment outcomes were retrospectively evaluated. RESULTS: The objective response rate (ORR) and disease control rate (DCR) for lenvatinib treatment were 25.0% and 95.0%, respectively, according to the Response Evaluation Criteria in Solid Tumors. The median progression-free survival (PFS) was 6.0 months, and the median overall survival (OS) was 10.5 months. Eleven patients experienced anorexia or fatigue, leading to a reduction in the dose of lenvatinib but not to a significant difference in the time to drug discontinuation. Importantly, there were no significant differences between the 11 anorexia/fatigue-suffering patients and the nine other patients with regard to PFS and OS. CONCLUSION: Lenvatinib can be efficacious and safe for treating advanced HCC patients previously treated with Atz/Bev, and AEs such as anorexia and general fatigue can be effectively managed without losing lenvatinib's therapeutic benefits.

症例は72歳,男性。年に1度の人間ドックで施行した血液検査にてCA19-9が62.2U/mLと高値であったため,CT検査を行ったところ膵頭部に腫瘍を指摘され,精査加療目的で当院紹介受診となった。腹部造影CT検査で膵頭部に21mm大の乏血性腫瘍を認め膵癌が疑われた。同部位に対して超音波内視鏡下穿刺吸引生検法を施行し,腺癌と病理診断された。以上から膵頭部癌と診断し,手術前化学療法施行後,幽門輪温存膵頭十二指腸切除術を施行した。手術検体の病理組織学的所見では,Hematoxylin Eosin染色で低分化型腺癌成分に加え,小型円形核,淡明な胞体を有する異型に乏しい細胞が蜂巣状に増生しており,免疫染色でsynaptophysin染色,chromogranin染色が共に陽性であったことから,充実胞巣状構造の成分はneuroendocrine neoplasmと診断した。腺癌およびneuroendocrine neoplasmがそれぞれ30%以上存在していたことから膵頭部原発Mixed neuroendocrine-non-neuroendocrine neoplasmと最終診断された。(著者抄録)

症例は72歳,男性。年に1度の人間ドックで施行した血液検査にてCA19-9が62.2U/mLと高値であったため,CT検査を行ったところ膵頭部に腫瘍を指摘され,精査加療目的で当院紹介受診となった。腹部造影CT検査で膵頭部に21mm大の乏血性腫瘍を認め膵癌が疑われた。同部位に対して超音波内視鏡下穿刺吸引生検法を施行し,腺癌と病理診断された。以上から膵頭部癌と診断し,手術前化学療法施行後,幽門輪温存膵頭十二指腸切除術を施行した。手術検体の病理組織学的所見では,Hematoxylin Eosin染色で低分化型腺癌成分に加え,小型円形核,淡明な胞体を有する異型に乏しい細胞が蜂巣状に増生しており,免疫染色でsynaptophysin染色,chromogranin染色が共に陽性であったことから,充実胞巣状構造の成分はneuroendocrine neoplasmと診断した。腺癌およびneuroendocrine neoplasmがそれぞれ30%以上存在していたことから膵頭部原発Mixed neuroendocrine-non-neuroendocrine neoplasmと最終診断された。(著者抄録)

エネルギー産生栄養素とは,たんぱく質,脂質,炭水化物に分類される宿主のエネルギーとして利用される成分である。エネルギー産生栄養素には,体に必要な筋肉,内臓,血管などさまざまな組織の構成成分を供給するとともに,脳をはじめとして生体活動を維持するために日々使用するエネルギーを供給する役割を担っている。さらに,炭水化物の一部は,食物繊維という消化酵素で分解されることなく,大腸に存在する腸内細菌の栄養素として利用される成分を含む。本稿では,エネルギー産生栄養素の代謝の代表的なプロセスを紹介するとともに食物繊維に関し最新の研究動向を紹介する。(著者抄録)

ビタミンとは,三大栄養素などのエネルギー産生栄養素に比べ微量ではあるものの,人体の機能を正常に保つため必要な有機化合物である。ヒトは,三大栄養素を代謝してエネルギー貯蔵分子であるATPに変換する生体内酵素反応において,特定のビタミン(B群,C)やミネラル(鉄,マグネシウム)を必要とする。さらに,ヒトは自ら消化酵素をもたない食物繊維やポリフェノールの代謝を腸内細菌叢に依存し,それが生産するビタミンや短鎖脂肪酸などの低分子代謝物をヒトの代謝に利用している。われわれは,バランスのよい食生活を通じ,自分達の代謝に必要な三大栄養素,ビタミン,ミネラルなどを摂取することはもちろん,腸内細菌の代謝に必要な食物繊維などのプレバイオティクスも摂取する必要がある。(著者抄録)

エネルギー産生栄養素とは,たんぱく質,脂質,炭水化物に分類される宿主のエネルギーとして利用される成分である。エネルギー産生栄養素には,体に必要な筋肉,内臓,血管などさまざまな組織の構成成分を供給するとともに,脳をはじめとして生体活動を維持するために日々使用するエネルギーを供給する役割を担っている。さらに,炭水化物の一部は,食物繊維という消化酵素で分解されることなく,大腸に存在する腸内細菌の栄養素として利用される成分を含む。本稿では,エネルギー産生栄養素の代謝の代表的なプロセスを紹介するとともに食物繊維に関し最新の研究動向を紹介する。(著者抄録)

ビタミンとは,三大栄養素などのエネルギー産生栄養素に比べ微量ではあるものの,人体の機能を正常に保つため必要な有機化合物である。ヒトは,三大栄養素を代謝してエネルギー貯蔵分子であるATPに変換する生体内酵素反応において,特定のビタミン(B群,C)やミネラル(鉄,マグネシウム)を必要とする。さらに,ヒトは自ら消化酵素をもたない食物繊維やポリフェノールの代謝を腸内細菌叢に依存し,それが生産するビタミンや短鎖脂肪酸などの低分子代謝物をヒトの代謝に利用している。われわれは,バランスのよい食生活を通じ,自分達の代謝に必要な三大栄養素,ビタミン,ミネラルなどを摂取することはもちろん,腸内細菌の代謝に必要な食物繊維などのプレバイオティクスも摂取する必要がある。(著者抄録)

Inflammatory myofibroblastic tumor (IMT) is a rare tumor composed of myofibroblasts with inflammatory blood cell infiltration. It commonly occurs in the lungs and rarely in the esophagus. We herein report a valuable case of IMT originating in the esophagus. A 60-year-old Japanese woman with dysphagia had a large subepithelial lesion (SEL) in the cervical esophagus, which was 15 cm in length. Surgical resection was performed to confirm the pathological diagnosis and improve the symptoms. The postoperative diagnosis was IMT composed of multiple nodules. There was no recurrence or metastasis within one year after surgery.

The combination therapy of atezolizumab, an anti-programmed cell death ligand-1 antibody, plus bevacizumab (Atz/Bev) is widely used to treat patients with advanced hepatocellular carcinoma (HCC). The development of polymyalgia rheumatica (PMR) during immune checkpoint inhibitor therapy for patients with HCC has not been reported to date. Two patients who developed PMR during Atz/Bev therapy for advanced HCC are reported. Both patients developed fever, bilateral symmetrical shoulder pain, morning stiffness, and an elevated C-reactive protein level. Their symptoms improved rapidly with prednisolone (PSL) 15-20 mg/d, and their C-reactive protein levels decreased. In PMR, long-term low-dose PSL should be administered. In the present patients who developed PMR as immune-related adverse events, starting with a small dose of PSL resulted in rapid improvement of symptoms.

肝門部領域胆管癌においては肝葉切除術以上の広範肝切除術を要する症例が多い。広範肝切除術を施行する場合は術後合併症による死亡率が5%前後と高率であり,主な死因が肝不全であることから,高度黄疸例には術前胆道ドレナージを行うことが推奨される。一方で,肝門部領域胆管癌の黄疸を認める肝葉切除術であっても(1)黄疸が軽度であり,(2)全身状態および肝予備能が比較的良好で,(3)肝切除量が少なく,待機期間の短い例においては,術前胆道ドレナージの必要がないとも報告されている。これまでのエビデンスから,肝門部領域胆管癌の術前ドレナージ術は(1)残存予定側の肝領域に対して,(2)経乳頭的なドレナージ術が行われることが推奨されている。ドレナージ方法としては本邦ではENBDが推奨される傾向にあるが,感染のコントロールや術前診断が十分になされている症例に対してはEBSも許容されると考えられる。近年では胆管内留置のインサイド型プラスチックステントや細径のfully covered metallic stentを用いた術前ドレナージ術の試みも報告されている。本稿では肝門部領域胆管癌に対する手術前ドレナージについて最近の動向を踏まえて解説する。(著者抄録)

肝門部領域胆管癌においては肝葉切除術以上の広範肝切除術を要する症例が多い。広範肝切除術を施行する場合は術後合併症による死亡率が5%前後と高率であり,主な死因が肝不全であることから,高度黄疸例には術前胆道ドレナージを行うことが推奨される。一方で,肝門部領域胆管癌の黄疸を認める肝葉切除術であっても(1)黄疸が軽度であり,(2)全身状態および肝予備能が比較的良好で,(3)肝切除量が少なく,待機期間の短い例においては,術前胆道ドレナージの必要がないとも報告されている。これまでのエビデンスから,肝門部領域胆管癌の術前ドレナージ術は(1)残存予定側の肝領域に対して,(2)経乳頭的なドレナージ術が行われることが推奨されている。ドレナージ方法としては本邦ではENBDが推奨される傾向にあるが,感染のコントロールや術前診断が十分になされている症例に対してはEBSも許容されると考えられる。近年では胆管内留置のインサイド型プラスチックステントや細径のfully covered metallic stentを用いた術前ドレナージ術の試みも報告されている。本稿では肝門部領域胆管癌に対する手術前ドレナージについて最近の動向を踏まえて解説する。(著者抄録)

The diagnosis of bile duct tumors can be difficult at times. A transpapillary bile duct biopsy findings with endoscopic retrograde cholangiopancreatography sometimes contradict diagnostic imaging findings. In bile duct tumors, inflammatory polyps in the extrahepatic bile duct are relatively rare with extrahepatic cholangitis. The disease's clinical relevance, including its natural history and prognosis, is not always clear. We show here a rare case of an inflammatory polyp in the common bile duct. A 69-year-old woman with abdominal pain was diagnosed with cholangitis. The findings of contrast-enhanced computed tomography and magnetic resonance cholangiopancreatography suggested that she had extrahepatic cholangiocarcinoma. The examination and therapy of cholangitis were performed by endoscopic retrograde cholangiopancreatography. The cholangiography revealed a suspected tumor in the hilar bile duct with some common bile duct stones. Then, after endoscopic sphincterotomy to remove tiny common bile duct stones, further detailed examinations were performed at the same time using an oral cholangioscope revealed a papillary raised lesion with a somewhat white surface in the bile duct; a biopsy was conducted on the same spot, and epithelial cells with mild atypia appeared in the shape of a papilla. Since the malignant tumor or the intraductal papillary neoplasm of the bile duct could not be ruled out, extrahepatic bile duct resection was conducted with the patient's informed consent. Bile duct inflammatory polyp was the histopathological diagnosis.

次世代シークエンサーをはじめとする難培養性の細菌を解析する研究技術の発展により,腸内細菌叢と疾患の関連性を示す研究が爆発的進歩を遂げている。消化器癌においても例外ではなくそれぞれの癌に特徴的な細菌との関連性が数多く報告されている。本稿では,腸内細菌を研究するうえでの基礎的な研究方法を紹介するとともに消化器癌における腸内細菌叢の影響に関し包括的に述べる。(著者抄録)

次世代シークエンサーをはじめとする難培養性の細菌を解析する研究技術の発展により,腸内細菌叢と疾患の関連性を示す研究が爆発的進歩を遂げている。消化器癌においても例外ではなくそれぞれの癌に特徴的な細菌との関連性が数多く報告されている。本稿では,腸内細菌を研究するうえでの基礎的な研究方法を紹介するとともに消化器癌における腸内細菌叢の影響に関し包括的に述べる。(著者抄録)

Objective In general, surface ulceration in gastric gastrointestinal stromal tumor (GIST) is considered a malignant feature; however, the mechanism underlying its formation has not been evaluated in detail. In this study, we analyzed the factors involved in ulceration using resected specimens of gastric GIST. Methods A total of 48 samples were retrospectively analyzed. We examined the association of surface ulceration of gastric GIST with the MIB-1 labeling index, mitotic number, tumor size, endoscopic ultrasound (EUS) findings and growth pattern on computed tomography (CT). Results The proportion of men was significantly higher in the ulceration group than in the non-ulceration group (p=0.04146), whereas age was not significantly different between the groups. Tumor was significantly larger in the ulceration group than in the non-ulceration group (p=0.0048). There was no correlation between tumor size and ulcer number. The MIB-1 index was not related to ulceration, nor were EUS findings. The number of mitotic cells tended to be higher in the ulceration group than in the non-ulceration group (p=0.05988). Intraluminal growth pattern was strongly associated with ulceration (p=0.00019). After a multivariate analysis, the growth pattern was the only factor associated with ulceration of gastric GIST. Conclusion Although formation of surface ulceration in gastric GIST was partially associated with the degree of malignancy, the growth pattern was the most important factor associated with ulceration in gastric GIST.

Pancreatic ductal adenocarcinoma (PDAC) can be treated with surgery, chemotherapy, and radiotherapy. Despite medical progress in each field in recent years, it is still insufficient for managing PDAC, and at present, the only curative treatment is surgery. A typical pancreatic cancer is relatively easy to diagnose with imaging. However, it is often not recommended for surgical treatment at the time of diagnosis due to metastatic spread beyond the pancreas. Even if it is operable, it often recurs during postoperative follow-up. In the case of PDAC with a diameter of 10 mm or less, the 5-year survival rate is as good as 80% or more, and the best index for curative treatment is tumor size. The early detection of pancreatic cancer with a diameter of less than 10 mm or carcinoma in situ is critical. Here, we provide an overview of the current status of diagnostic imaging features and genetic tests for the accurate diagnosis of early-stage PDAC.

BACKGROUND AND AIM: In colorectal endoscopic submucosal dissection (ESD), post-ESD electrocoagulation syndrome (PECS) has been recognized as one of the major complications. There are no reports on the relationships between ESD findings and PECS. This study aims to evaluate the risk factors for PECS, including ESD findings such as muscularis propria exposure. METHODS: We performed a retrospective cohort study of patients who underwent colorectal ESD between January 2017 and December 2021 in Japan. The grade of injury to the muscle layer caused by ESD was categorized as follows: Grade 0, no exposure of muscularis propria; Grade 1, muscularis propria exposure; Grade 2, torn muscularis propria; and Grade 3, colon perforation. The risk factors for PECS, including injury to the muscle layer, were analyzed by univariate and multivariate analyses. RESULTS: Out of 314 patients who underwent colorectal ESD, PECS occurred in 28 patients (8.9%). The multivariate analysis showed that female sex (odds ratio [OR] 3.233; 95% confidence interval [95% CI]: 1.264-8.265, P = 0.014), large specimen size (≥ 40 mm) (OR 6.138; 95% CI: 1.317-28.596, P = 0.021), long procedure time (≥ 90 min) (OR 2.664; 95% CI: 1.053-6.742, P = 0.039), and Grade 1 or 2 injury to the muscle layer (OR 3.850; 95% CI: 1.090-13.61, P = 0.036) were independent risk factors for PECS. CONCLUSIONS: Injury to the muscle layer, such as exposure or tear, was identified as a novel independent risk factor for PECS. We should perform colorectal ESD carefully to avoid injuring the muscle layers.