柴田 知行

Abstract Background and study aims Esophageal endoscopic submucosal dissection (ESD) has a higher complication rate than gastric ESD. Scissor-type devices, including the stag beetle (SB) knife, are reportedly safer and have shorter procedure times than tip devices. To clarify the characteristics of the SB knife, we compared the treatment outcomes of esophageal ESD with a tip-type knife to those with an SB knife combination. Patients and methods Between January 2016 and March 2023, clinical data from 197 lesions in 178 patients who underwent esophageal ESD were analyzed retrospectively. Every lesion was assigned to either the tip-type group or the SB group based on the devices with which the submucosa was initially dissected. We compared procedure time and complications and analyzed the risk of muscular exposure using multivariate analysis. Results Procedure time was not significantly different between the tip-type and SB groups (60.3±42.2 min vs. 58.8±29.1 min). The variation in procedure time was significant according to F test P=0.002). Incidence of muscular exposure was significantly lower in the SB group than in the tip-type group (24.5% vs. 11.1%, P=0.016). These differences were significant in resected specimens larger than 21 mm. Procedure time over 60 minutes (odds ratio [OR] 2.5, 95% confidence interval [CI]: 1.15–5.42, P=0.02) was a risk factor for muscular exposure, and submucosal dissection with an SB knife was a safety factor (OR 0.4, 95% CI: 0.18–0.89, P=0.02). Conclusions Performing esophageal ESD with an SB knife is a safe procedure with less variation in procedure time and less muscule exposure.

Helicobacter pylori induces DNA methylation in gastric mucosa, which links to gastric cancer (GC) risk. In contrast, CpG island methylator phenotype (CIMP) is defined as high levels of cancer-specific methylation and provides distinct molecular and clinicopathological features of GC. The association between those two types of methylation in GC remains unclear. We examined DNA methylation of well-validated H. pylori infection associated genes in GC and its adjacent mucosa and investigated its association with CIMP, various molecular subtypes and clinical features. We studied 50 candidate loci in 24 gastric samples to identify H. pylori infection associated genes. Identified loci were further examined in 624 gastric tissue from 217 primary GC, 217 adjacent mucosa, and 190 mucosae from cancer-free subjects. We identified five genes (IGF2, SLC16A2, SOX11, P2RX7, and MYOD1) as hypermethylated in H. pylori infected gastric mucosa. In non-neoplastic mucosa, methylation of H. pylori infection associated genes was higher in patients with GC than those without. In primary GC tissues, higher methylation of H. pylori infection associated genes correlated with CIMP-positive and its related features, such as MLH1 methylated cases. On the other hand, GC with lower methylation of these genes presented aggressive clinicopathological features including undifferentiated histopathology, advanced stage at diagnosis. H. pylori infection associated DNA methylation is correlated with CIMP, specific molecular and clinicopathological features in GC, supporting its utility as promising biomarker in this tumor type.

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.

(1) Background: This study aimed to investigate clinical outcomes for cabozantinib in clinical practice in patients with advanced hepatocellular carcinoma (HCC) previously treated with atezolizumab plus bevacizumab (Atz/Bev), with a focus on whether patients met criteria of Child-Pugh Class A and Eastern Cooperative Oncology Group performance status (ECOG-PS) score 0/1 at baseline. (2) Methods: Eleven patients (57.9%) met the criteria of both Child-Pugh class A and ECOG-PS score 0/1 (CP-A+PS-0/1 group) and eight patients (42.1%) did not (Non-CP-A+PS-0/1 group); efficacy and safety were retrospectively evaluated. (3) Results: Disease control rate was significantly higher in the CP-A+PS-0/1 group (81.1%) than in the non-CP-A+PS-0/1 group (12.5%). Median progression-free survival, overall survival and duration of cabozantinib treatment were significantly longer in the CP-A+PS-0/1 group (3.9 months, 13.4 months, and 8.3 months, respectively) than in the Non-CP-A+PS-0/1 group (1.2 months, 1.7 months, and 0.8 months, respectively). Median daily dose of cabozantinib was significantly higher in the CP-A+PS-0/1 group (22.9 mg/day) than in the non-CP-A+PS-0/1 group (16.9 mg/day). (4) Conclusions: Cabozantinib in patients previously treated with Atz/Bev has potential therapeutic efficacy and safety if patients have good liver function (Child-Pugh A) and are in good general condition (ECOG-PS 0/1).

The combination of atezolizumab plus bevacizumab (Atz/Bev) is now widely used in clinical practice as a first-line treatment for patients with advanced hepatocellular carcinoma (HCC). However, the established regimen for post-treatment after Atz/Bev is unknown. We investigated the efficacy and safety of cabozantinib in patients previously treated with Atz/Bev in real clinical practice, with a focus on whether patients met criteria of Child-Pugh Class A and Eastern Cooperative Oncology Group performance status (ECOG-PS) score 0/1 at baseline. Our results suggest that cabozantinib in patients with advanced HCC previously treated with Atz/Bev can be expected to yield similar outcomes to those seen in the CELESTIAL trial conducted using cabozantinib for post-sorafenib treatment if patients have good liver function and are in good general condition.(1) Background: This study aimed to investigate clinical outcomes for cabozantinib in clinical practice in patients with advanced hepatocellular carcinoma (HCC) previously treated with atezolizumab plus bevacizumab (Atz/Bev), with a focus on whether patients met criteria of Child-Pugh Class A and Eastern Cooperative Oncology Group performance status (ECOG-PS) score 0/1 at baseline. (2) Methods: Eleven patients (57.9%) met the criteria of both Child-Pugh class A and ECOG-PS score 0/1 (CP-A+PS-0/1 group) and eight patients (42.1%) did not (Non-CP-A+PS-0/1 group); efficacy and safety were retrospectively evaluated. (3) Results: Disease control rate was significantly higher in the CP-A+PS-0/1 group (81.1%) than in the non-CP-A+PS-0/1 group (12.5%). Median progression-free survival, overall survival and duration of cabozantinib treatment were significantly longer in the CP-A+PS-0/1 group (3.9 months, 13.4 months, and 8.3 months, respectively) than in the Non-CP-A+PS-0/1 group (1.2 months, 1.7 months, and 0.8 months, respectively). Median daily dose of cabozantinib was significantly higher in the CP-A+PS-0/1 group (22.9 mg/day) than in the non-CP-A+PS-0/1 group (16.9 mg/day). (4) Conclusions: Cabozantinib in patients previously treated with Atz/Bev has potential therapeutic efficacy and safety if patients have good liver function (Child-Pugh A) and are in good general condition (ECOG-PS 0/1).

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 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.

BACKGROUND/AIM: Lymphoid follicles hyperplasia (LH) is sometimes observed in the normal colon as small, round, yellowish-white nodules. LH is associated with food hypersensitivity and bowel symptoms and histologically characterized as intense infiltration of lymphocytes or plasmacytes. It is suggested that LH represents inflammatory immune response in the colonic mucosa. We investigated the presence of LH in the normal colonic mucosa and its association with incidence of colorectal lesions including colorectal cancer, adenoma and hyperplastic polyp. PATIENTS/METHODS: 605 participants undergoing colonoscopy for various indications were enrolled. Presence of LH in the proximal colon (appendix, cecum and the ascending colon) was observed using the blue laser imaging (BLI) endoscopy, a new generation image enhanced endoscopy (IEE) system. LH was defined as well demarcated white nodules. Elevated LH with erythema was distinguished as LH severe. Association between presence of LH and occurrence of colorectal lesions was investigated. RESULTS: Prevalence of all colorectal lesions and adenoma were significantly lower in LH severe group compared to the LH negative group (P = 0.0008, 0.0009, respectively). Mean number of all colorectal lesions and adenoma were also lower in LH severe group compared to the LH negative group (P = 0.005, 0.003 respectively). The logistic regression with adjustment for gender and age demonstrated that presence of LH severe held significantly lower risk of all colorectal lesions (OR = 0.48, 95%CI = 0.27-0.86) and adenoma (OR = 0.47, 95%CI = 0.26-0.86). CONCLUSION: LH in the colonic mucosa visualized by IEE is useful endoscopic finding to predict risk of colorectal adenoma.

Background: Anisakiasis is a parasitic disease caused by the consumption of raw or undercooked fish that is infected with Anisakis third-stage larvae. In countries, such as Japan, Italy, and Spain, where people have a custom of eating raw or marinated fish, anisakiasis is a common infection. Although anisakiasis has been reported in the gastrointestinal tract in several countries, reports of anisakiasis accompanied by cancer are rare. Case presentation: We present the rare case of a 40-year-old male patient with anisakiasis coexisting with mucosal gastric cancer. Submucosal gastric cancer was suspected on gastric endoscopy and endoscopic ultrasonography. After laparoscopic distal gastrectomy, granulomatous inflammation with Anisakis larvae in the submucosa was pathologically revealed beneath mucosal tubular adenocarcinoma. Histological and immunohistochemical investigation showed cancer cells as intestinal absorptive-type cells that did not produce mucin. Conclusion: Anisakis larvae could have invaded the cancer cells selectively because of the lack of mucin in the cancerous epithelium. Anisakiasis coexisting with cancer is considered reasonable rather than coincidental. In cancer with anisakiasis, preoperative diagnosis may be difficult because anisakiasis leads to morphological changes in the cancer.

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.

OBJECTIVES: Comprehensive assessments of the long-term outcomes of endoscopic submucosal dissection (ESD) for early gastric cancer (EGC) in the elderly are unavailable. We aimed to create a scoring system to predict the long-term prognosis after ESD for EGC among patients aged ≥75 years. METHODS: We conducted retrospective studies of two cohorts: a single-center cohort (2006-2011) for developing the scoring system, and a multicenter cohort for validating the developed system (2012-2016). In the development cohort, factors related to death after ESD were identified using multivariable Cox regression analysis, and a predictive scoring system was developed. In the validation cohort, the scoring system was validated in 295 patients. RESULTS: In the development cohort, Charlson comorbidity index (CCI) ≥3 (hazard ratio [HR] 3.017), high psoas muscle index (PMI) (HR 2.206), and age ≥80 years (HR 1.978) were significantly related to overall survival after ESD. Therefore, high CCI, low PMI, and age ≥80 years were assigned 1 point each. The patients were categorized into low (≤1 point) and high (≥2 points) score groups based on their total scores. In the validation cohort, 184 and 111 patients were assigned to the low- and high-score groups, respectively. In comparisons based on Kaplan-Meier curves, the 5-year survival rate was 91.5% in the low-score group and 57.8% in the high-score group (log-rank test; P < 0.001). CONCLUSION: Our scoring system including high CCI, low PMI, and age ≥80 years could stratify the long-term prognosis of elderly patients aged ≥75 years after ESD for EGC.

In inflammatory bowel disease, including Crohn's disease and ulcerative colitis, an excessive immune response due primarily to T-cell lymphocytes causes inflammation in the gastrointestinal tract. Lesions in Crohn's disease can occur anywhere in the gastrointestinal tract, i.e., from the oral cavity to the anus. Endoscopically, aphthoid lesions/ulcers believed to be initial lesions progress to discrete ulcers, which coalesce to form a longitudinal array and progress to longitudinal ulcers with a cobblestone appearance, which is a typical endoscopic finding. Before long, complications such as strictures, fistulas, and abscesses form. Lesions in ulcerative colitis generally extend continuously from the rectum and diffusely from a portion of the colon to the entire colon. Endoscopically, lack of vascular pattern, fine granular mucosa, erythema, aphthae, and small yellowish spots are seen in mild cases; coarse mucosa, erosions, small ulcers, bleeding (contact bleeding), and adhesion of mucous, bloody, and purulent discharge in moderate cases; and widespread ulcers and marked spontaneous bleeding in severe cases.

Background: The relationship between pancreatic ductal adenocarcinoma (PDAC) and the intestinal environment is not fully understood. The purpose of this study was to elucidate the characteristics of the intestinal environment in PDAC. Methods: We performed a case-control study of 5 Japanese patients with unresectable PDAC located in the body or tail (PDAC-bt). The number of patients analyzed was limited for this preliminary study. We included 68 healthy subjects, herein control, of pre-printed study in the preliminary study. 16S rRNA amplicon sequencing and metabolomic analysis were performed using fecal samples from the subjects. Results: There was no difference in the Shannon index and Principal Coordinate Analysis between PDAC-bt and the control. However, a significant increase in oral-associated bacteria (Actinomyces, Streptococcus, Veillonella, Lactobacillus) was observed. A significant decrease of Anaerostipes was demonstrated in the feces of PDAC-bt compared with the control. The intestinal propionic acid and deoxycholic acid were significantly lower in PDAC-bt compared with the control. Conclusions: We showed that the intestinal environment of PDAC-bt is characterized by an increase in oral-associated bacteria and an imbalance of metabolites but without changes in alpha and beta diversity of the gut microbiota profiles.Clinical Trial Registration: www.umin.ac.jp, UMIN 000041974, 000023675, 000023970.

Endoscopy is widely applied in the examination of gastric cancer. However, extensive knowledge and experience are required, owing to the need to examine the lesion while manipulating the endoscope. Various diagnostic support techniques have been reported for this examination. In our previous study, segmentation of invasive areas of gastric cancer was performed directly from endoscopic images and the detection sensitivity per case was 0.98. This method has challenges of false positives and computational costs because segmentation was applied to all healthy images that were captured during the examination. In this study, we propose a cascaded deep learning model to perform categorization of endoscopic images and identification of the invasive region to solve the above challenges. Endoscopic images are first classified as normal, showing early gastric cancer and showing advanced gastric cancer using a convolutional neural network. Segmentation on the extent of gastric cancer invasion is performed for the images classified as showing cancer using two separate U-Net models. In an experiment, 1208 endoscopic images collected from healthy subjects, 533 images collected from patients with early stage gastric cancer, and 637 images from patients with advanced gastric cancer were used for evaluation. The sensitivity and specificity of the proposed approach in the detection of gastric cancer via image classification were 97.0% and 99.4%, respectively. Furthermore, both detection sensitivity and specificity reached 100% in a case-based evaluation. The extent of invasion was also identified at an acceptable level, suggesting that the proposed method may be considered useful for the classification of endoscopic images and identification of the extent of cancer invasion.

BACKGROUND: The management of bleeding during endoscopic submucosal dissection (ESD) is critical and related to the procedure time. We collaborated on a new image enhancement algorithm with parameter optimization for clinical use being developed by FUJIFILM Co. and processed white light image data offline to evaluate the effectiveness of this technology. This study aims to evaluate the clinical usefulness of this technology. METHODS: Eighteen video scenes of bleeding points from 5 gastric ESDs were selected and processed by the new image enhancement algorithm. The time until a bleeding point was found, visibility of a bleeding point and color abnormality of the submucosal layer were evaluated by ESD experts, ESD trainees, and endoscopy trainees. The color differences between the bleeding point and the surroundings in CIE- L*a*b* color space were calculated in the original and enhanced images. RESULTS: The time until a bleeding point was found in the enhanced videos was significantly shorter than that in the original videos (11.10 seconds vs. 13.85 seconds) (P=0.017). On a 5-point (-2 to +2) Likert scale of visibility, the enhanced image was slightly superior to the original (+0.45), and the appearance of the submucosa was comparable between images (+0.14). The color difference among the bleeding areas on the enhanced images were significantly larger than that on the original images (10.93 vs. 8.36). CONCLUSION: This novel image enhancement algorithm emphasizes the color difference between a bleeding point and the surrounding area, which would help find bleeding points faster during ESD for the less experienced endoscopists.

Gastric endoscopic submucosal dissection (ESD) is increasingly performed in patients receiving antithrombotic therapy. Second-look endoscopy (SLE) has been performed empirically in several clinical settings. We investigated whether SLE omission was associated with an increased risk of postESD bleeding in all patients, including those administered antithrombotic agents. Between July 2016 and June 2018, 229 patients were treated with a clinical pathway for gastric ESD that involved SLE on the day after ESD (SLE group). Between September 2018 and May 2020, 215 patients were treated using a clinical pathway that did not include SLE (nonSLE group). We retrospectively compared the incidence of postESD bleeding among the propensity score-matched cohorts and determined the risk factors for postESD bleeding using multivariate analysis. The propensity score-matched cohorts showed no significant differences in the incidence of postESD bleeding between the SLE (3.2%) and nonSLE (5.1%) groups. Multivariate analysis revealed that the presence of lesions in the lower gastric body (adjusted odds ratio [OR] 2.17, 95% confidence interval [CI] 1.06-4.35, P.03) was a significant risk factor for postESD bleeding during admission, whereas resected specimen size ≥ 40 mm (adjusted OR 3.21, 95% CI 1.19-8.19, P.02) and antiplatelet therapy (adjusted OR 4.16, 95% CI 1.47-11.80, P.007) were significant risk factors after discharge. Complete omission of SLE after gastric ESD does not increase postESD bleeding in clinical practice.

Small intestinal tumors (adenoma and adenocarcinoma, SIT) are rare, and their microRNA (miRNA) expression profiles have not been established. Previously, we reported a relationship between miRNA expression profiles and the development, growth, morphology, and anticancer drug resistance of colorectal tumors. Here, we demonstrate that the miRNA expression profile of SIT is significantly different from those of tumors of the colon. We compared the onco-related miRNA expression profiles of SIT and colorectal tumors and found them to be different from each other. The expressions of miR-143 and miR-145 were frequently downregulated in SIT and colorectal tumors but not in sessile serrated adenoma/polyp tumors. The profiles of SIT and colorectal carcinomas of miR-7, miR-21, and miR-34a were considerably different. Upregulation of miR-31 expression was not found in any SIT cases. Our data suggested that miR-143 and miR-145 might act as anti-oncomirs common to adenocarcinoma of the small intestine, similar to those of colorectal adenoma and other cancers. However, the expression profiles of the other miRNAs of SIT were significantly different from those of colorectal tumors. These findings contribute useful insights into the tumor development and diagnosis of SIT.

AIM: The present study evaluated the efficacy and safety of ramucirumab (RAM) in clinical practice as post-treatment, following atezolizumab plus bevacizumab (Atz/Bev) for advanced hepatocellular carcinoma (HCC) with alpha-fetoprotein (AFP) levels of ≥400 ng/ml. PATIENTS AND METHODS: Of the 77 patients treated with Atz/Bev at our institution, 13 patients for whom RAM was introduced as post-treatment following Atz/Bev were enrolled in this retrospective study. There were 9 patients (69.2%) with Child-Pugh A and 11 patients (84.6%) for whom RAM was initiated as 3rd- or later-line therapy. The median AFP level was 2259 ng/ml. RESULTS: The objective response rate by Response Evaluation Criteria in Solid Tumours at 6 weeks was 15.4%, and the disease control rate was 69.2%. The median time to progression was 3.0 months; AFP level decreased at 2 weeks in 11 patients (84.6%) and at 6 weeks in seven patients (53.8%). The most common adverse events (AEs) within 6 weeks were ascites, peripheral oedema, and proteinuria, while grade 3 AEs occurred in six patients (46.2%). Albumin-bilirubin scores at both 4 and 6 weeks were significantly worse than those at baseline. CONCLUSION: In HCC patients with AFP levels of ≥400 ng/mL, RAM after Atz/Bev is expected to be an effective treatment option. Careful attention should be paid to the development of AEs and deterioration of liver function, especially when RAM is used as 3rd- or later-line therapy. Additional studies are needed to confirm the efficacy and safety of RAM as 2nd-line treatment after Atz/Bev in Child-Pugh A patients.

The following are some common features of ulcerative colitis (UC) and Crohn's disease (CD) on transabdominal ultrasonography (TUS). UC, which consists primarily of mucosal inflammation, is seen on TUS as wall thickening with preserved layer structure continuing from the rectum in the active phase of UC. Inflammation confined to the mucosa is seen as thickening of the mucosal/submucosal layers. When the inflammation becomes severe, the echogenicity of the submucosal layer decreases and the layer structure becomes indistinct. CD, which consists primarily of discontinuous transmural inflammation, shows more pronounced hypoechoic wall thickening than UC at the transmural inflammation. On TUS, the layer structure becomes indistinct and gradually disappears due to the depth of the myriad inflammation during the active phase of CD. It is important to evaluate the changes in wall thickening and layer structure when diagnosing UC and CD with TUS. In addition, diagnostic techniques such as color Doppler and contrast-enhanced ultrasonography, which can be used to assess blood flow, and elastography, which can be used to evaluate stiffness, are also used. Thus, TUS is a noninvasive and convenient modality that shows promise as a useful examination for diagnosis of UC and CD.

There are various types of pancreatic neoplasms, and their prognosis and treatment methods are different. Therefore, accurate diagnosis is important to determine the best treatment strategy. Transabdominal ultrasonography is frequently used as a screening examination for diagnostic imaging of pancreatic neoplasms. In this review, we have focused on the characteristics of ultrasonic findings for relatively rare pancreatic neoplasms.

Pancreatic neuroendocrine neoplasms (PNENs) are relatively rare with a reported incidence of 1-2/100,000 and generally thought to originate from the precursor of the neuroendocrine cells including the islet and the pancreatic duct cells. About 65% of PNENs are non-functional. While insulinomas and gastrinomas are the most common functional PNENs, ACTH-producing PNENs are extremely rare. We herein present an extremely rare case of a patient with Cushing's syndrome caused by PNEN. A 46-year-old woman with edema in bilateral lower extremities and moon face was admitted with a suspicious pancreatic tumor. Enhanced computed tomography and endoscopic ultrasonography revealed a pancreatic tumor. The final diagnosis of ACTH-producing PNEN with Cushing's syndrome was based on clinical and biochemical test results and endocrinological studies. The symptoms associated Cushing's syndrome improved after pancreaticoduodenectomy for PNEN.

Upper gastrointestinal endoscopy is widely performed to detect early gastric cancers. As an automated detection method for early gastric cancer from endoscopic images, a method involving an object detection model, which is a deep learning technique, was proposed. However, there were challenges regarding the reduction in false positives in the detected results. In this study, we proposed a novel object detection model, U-Net R-CNN, based on a semantic segmentation technique that extracts target objects by performing a local analysis of the images. U-Net was introduced as a semantic segmentation method to detect early candidates for gastric cancer. These candidates were classified as gastric cancer cases or false positives based on box classification using a convolutional neural network. In the experiments, the detection performance was evaluated via the 5-fold cross-validation method using 1208 images of healthy subjects and 533 images of gastric cancer patients. When DenseNet169 was used as the convolutional neural network for box classification, the detection sensitivity and the number of false positives evaluated on a lesion basis were 98% and 0.01 per image, respectively, which improved the detection performance compared to the previous method. These results indicate that the proposed method will be useful for the automated detection of early gastric cancer from endoscopic images.

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.