田中 浩敬

胆道癌は早期発見が難しく,正確な質的診断と進展度評価が重要である。超音波内視鏡(EUS)は胆道やその周囲の観察に優れ,質的診断や血管浸潤評価に有用である。管腔内超音波(IDUS)は胆管内の詳細な構造を高解像度で描出し,深達度診断や鑑別診断に優れる。とくに肝外胆管癌や乳頭部癌では両者を併用することで,術前診断の精度が向上する。EUSとIDUSは互いの長所を補完する重要な検査である。超音波造影剤を用いた造影EUSのほかに,近年では微小血流評価やエラストグラフィー,AI技術の応用も期待されている。(著者抄録)

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.

AIM: To investigate the characteristics and prognosis of patients with advanced hepatocellular carcinoma (HCC) treated with atezolizumab and bevacizumab (Atz/Bev) who achieved a complete response (CR) according to the modified Response Evaluation Criteria in Solid Tumors (mRECIST). METHODS: A total of 120 patients with Eastern Cooperative Oncology Group performance status (PS) 0 or 1 and Child-Pugh A at the start of Atz/Bev treatment were included. Barcelona Clinic Liver Cancer stage C was recorded in 59 patients. RESULTS: The CR rate with Atz/Bev alone was 15.0%. The median time to CR was 3.4 months, and the median duration of CR was 15.6 months. A significant factor associated with achieving CR with Atz/Bev alone was an AFP ratio of 0.34 or less at 3 weeks. Adding transarterial chemoembolization (TACE) in the six patients who achieved a partial response increased the overall CR rate to 20%. Among the 24 patients who achieved CR, the median progression-free survival was 19.3 months, the median overall survival was not reached, and 14 patients (58.3%) were able to discontinue Atz/Bev and achieve a drug-free status. Twelve of these patients developed progressive disease (PD), but eleven successfully received post-PD treatments and responded well. CONCLUSIONS: Achieving CR by mRECIST using Atz/Bev alone or with additional TACE can be expected to offer an extremely favorable prognosis.

The relationship between antitumor response and tumor marker changes was evaluated in patients with advanced hepatocellular carcinoma treated with durvalumab plus tremelimumab (Dur/Tre). Forty patients were enrolled in this retrospective evaluation of treatment outcomes. According to the Response Evaluation Criteria for Solid Tumors version 1.1 at 8 weeks, the objective response (OR) rate was 25% and the disease control (DC) rate was 57.5%. The median alpha-fetoprotein (AFP) ratio at 4 weeks was 0.39 in patients who achieved OR at 8 weeks (8W-OR group), significantly lower than the 1.08 in the non-8W-OR group (p = 0.0068); however, it was 1.22 in patients who did not achieve DC at 8 weeks (non-8W-DC group), significantly higher than the 0.53 in the 8W-DC group (p = 0.0006). Similarly, the median des-γ-carboxy-prothrombin (DCP) ratio at 4 weeks was 0.15 in the 8W-OR group, significantly lower than the 1.46 in the non-8W-OR group (p < 0.0001); however, it was 1.23 in the non-8W-DC group, significantly higher than the 0.49 in the 8W-DC group (p = 0.0215). Early changes in tumor markers after Dur/Tre initiation were associated with antitumor response. In particular, changes in AFP and DCP at 4 weeks may offer useful biomarkers for early prediction of both response and progressive disease following Dur/Tre.

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.

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.