橋本 千樹

BACKGROUND: Cancer gene panel testing (CGP) helps comprehensively analyze a large number of genes, extracting genetic information from the genome profile to aid treatment plans and drug therapy. Advances in drug therapy and surgical treatment for intrahepatic cholangiocarcinoma (ICC) have improved patient outcomes; however, it remains a typical intractable cancer with a poor prognosis. ICC is one of the key tumors for which effective treatment may be identified through CGP testing. This study aimed to identify ICC harboring actionable genetic variants using contrast-enhanced ultrasonography (CE-US). METHODS: We enrolled 26 ICC patients who underwent CE-US before chemotherapy or surgery. Three ultrasound specialists reviewed the images by consensus and assessed the imaging features, including vascularity. Pathological data were reviewed after diagnosis using CE-US. We retrospectively analyzed distinctive CE-US findings in patients with ICC with actionable genetic variants. RESULTS: Twelve ICC patients had actionable gene variants, including four FGFR2 fusions, one FGFR2 rearrangement, six IDH1 mutations, and one BRAF V600E mutation. Univariate analysis showed significant differences in bile duct invasion (p = 0.0217) and blood vessel penetration within the tumor (p = 0.0012). Multivariable logistic regression identified blood vessel penetration within the tumor (OR = 18.275; 95% CI: 1.331-250.925; p = 0.0297) as independently associated with actionable gene variants. CONCLUSION: Patients with ICC and blood vessel penetration on CE-US should be considered for CGP testing.

In Japan, the establishment of diagnostic criteria for acute-on-chronic liver failure (ACLF) in 2022 has increased the focus on alcoholic hepatitis. Most hospitals in Japan lack specialized treatment units or psychiatrists for managing alcohol use disorders, leaving hepatologists to handle various aspects of the disease-a challenging task. This study retrospectively investigated the outcomes of alcoholic hepatitis in a typical Japanese hospital setting, stratified by ACLF diagnosis and other features, with the aim of identifying areas for possible improvement. We conducted a retrospective analysis of 88 patients hospitalized with alcoholic hepatitis, reviewing records for the diagnosis of ACLF or related conditions, development of delirium tremens (DT), risk factors, and patient outcomes. Patients meeting the Japanese criteria for ACLF or related conditions had significantly worse survival outcomes. DT developed in 13 patients, with low platelet counts and elevated γ-glutamyl transpeptidase levels identified as risk factors. Prophylactic oral benzodiazepines were found safe and significantly associated with preventing DT. Onset of DT during hospitalization did not measurably impact survival prognosis, but DT patients showed a tendency to break contact with our hospital and critical events may have been missed. While under hepatologist care, patients typically maintained sobriety, but relapse into alcohol-related health problems frequently occurred after follow-up was discontinued. In Japan, hepatologists may be missing important events with alcoholic hepatitis after follow-up discontinuation, especially in patients with DT. Therefore, integrated and collaborative care, particularly a psychosocial approach providing behavioural support, may reduce risk of relapse and improve patient prognosis. TRIAL REGISTRATION: All study protocols were reviewed and approved by the ethics committee at Fujita Health University School of Medicine (approval no. HM23-213).

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.

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.

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.

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.

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.