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Simple Summary: This study presents a comprehensive analysis of gene expression profiles in early-stage gastric cancer (GC) lesions, focusing on the background gastric mucosa in patients who underwent endoscopic submucosal dissection. We aimed to reveal differences in gene expression profiles between patients with single and multiple GCs and to construct a scoring system for distinguishing between these two conditions. Using four biopsied specimens per patient, lesion-specific gene profiles were derived and analyzed using DNA microarrays. Overall, 21 genes exhibiting distinct expression profiles in relation to the background gastric mucosa were extracted. A scoring system was constructed by assigning weighted values to these 21 genes, with an optimal cutoff value of −2.574, yielding 85.7% sensitivity and specificity. The findings indicate that, compared to patients with a single GC, patients with multiple GCs have a more similar gene expression between the background gastric mucosa and the GC lesions. Background: This study aimed to perform a comprehensive gene expression analysis in patients with early-stage gastric cancer (EGC) to identify gene expression profiles specific to gastric cancer (GC) lesions. Methods: Biopsy specimens were collected from one EGC lesion and three background mucosal areas of patients scheduled for endoscopic submucosal dissection (ESD). Lesion-specific gene profiles in these four biopsies were analyzed using DNA microarrays. Patients with concurrent EGCs at the time of an ESD or a history of GC were classified into the multiple GC group (n = 26), while those without such histories were assigned to the single GC group (n = 74). Results: After excluding patients with heterogeneous factors, 55 patients were analyzed. Twenty-one differential genes exhibiting distinct mean expression profiles stratified by background gastric mucosa were extracted between the single and multiple GC groups. A scoring system constructed using these genes to calculate the weighted expression values for each patient, with an optimal cutoff value of −2.574, yielded a sensitivity and specificity of 85.7%. Conclusions: This study identified the different gene expression profiles between synchronous and metachronous multiple GCs and single GCs in patients with EGC. The developed scoring system has potential to distinguish between single and multiple GCs. [ABSTRACT FROM AUTHOR]

Simple Summary: Colorectal neoplasia developing from ulcerative colitis mucosa (CRNUC) can be divided into ulcerative colitis-associated neoplasia (UCAN) and non-UCAN; however, it is often difficult to distinguish UCAN from non-UCAN during a biopsy diagnosis. We investigated whether a genomic analysis could improve the diagnostic accuracy of UCAN using biopsy specimens. The pathological diagnosis of biopsy specimens using only hematoxylin and eosin (HE) staining had a sensitivity of 33% and an accuracy of 38% for UCAN diagnosis. On the other hand, the combination of the HE pathology and p53 immunohistochemical staining had a sensitivity of 73% and an accuracy of 85% for UCAN diagnosis, while the combination of HE staining and a TP53 mutation had a sensitivity of 87% and an accuracy of 88% for UCAN diagnosis. An evaluation of TP53 mutations in biopsy specimens may be useful for diagnosing UCAN. However, further studies with larger sample sizes are required before this can be applied in clinical practice. Background/Objectives: Colorectal neoplasia developing from ulcerative colitis mucosa (CRNUC) can be divided into ulcerative colitis-associated neoplasia (UCAN) and non-UCAN; however, it is often difficult to distinguish UCAN from non-UCAN during a biopsy diagnosis. We investigated whether a genomic analysis could improve the diagnostic accuracy of UCAN using biopsy specimens. Methods: In step 1, 14 CRNUCs were used to examine whether the genomic landscape of biopsy and resection specimens matched. In step 2, we investigated the relationship between the genomic landscapes and the pathological diagnosis of 26 CRNUCs. The cancer genome was analyzed by deep sequencing using a custom panel of 27 genes found to be mutated in our previous CRNUC analysis. Results: In step 1, of the 27 candidate genes, 14 were mutated. The concordance rate of the pathogenic mutations in these 14 genes between the biopsy and resection specimens was 29% (4/14), while that of the pathogenic mutations in TP53 and KRAS was 79% (11/14). In step 2, the pathological diagnosis of biopsy specimens using only hematoxylin and eosin (HE) staining had a sensitivity of 33% and an accuracy of 38% for UCAN diagnosis. On the other hand, the combination of the HE pathology and p53 immunohistochemical staining had a sensitivity of 73% and an accuracy of 85% for UCAN diagnosis, while the combination of HE staining and a TP53 mutation had a sensitivity of 87% and an accuracy of 88% for UCAN diagnosis. Conclusions: An evaluation of TP53 mutations in biopsy specimens may be useful for diagnosing UCAN. However, further studies with larger sample sizes are required before this can be applied in clinical practice. [ABSTRACT FROM AUTHOR]

Simple Summary: Although comprehensive genomic profiling (CGP) tests have been covered under the Japanese national health insurance program, the utility and issues of CGP tests have not been clarified. We retrospectively reviewed 115 patients with incurable pancreatic cancer (IPC) who underwent CGP tests in a Japanese cancer referral center from November 2019 to August 2021. Eight cases (6.9%) were diagnosed as tumor mutation burden-high and/or microsatellite instability-high. The gene mutation rates of KRAS/TP53/CDKN2A/SMAD4 were 93.0/83.0/53.0/25.2%, respectively. Twenty-five patients (21.7%) had homologous recombination deficiency (HRD)-related genetic mutations. Six patients (5.2%) underwent gene-matched therapy based on results of CGP tests. The median overall survival (OS) was significantly longer in the HRD (+) group. In multivariate analysis, HRD-related gene mutation was an independent prognostic factor associated with favorable OS. CGP tests for patients with IPC have the potential utility of detecting HRD-related gene mutations as prognostic factors as well as a therapeutic search. Although comprehensive genomic profiling (CGP) tests have been covered under the Japanese national health insurance program since 2018, the utility and issues of CGP tests have not been clarified. We retrospectively reviewed 115 patients with incurable pancreatic cancer (IPC) who underwent CGP tests in a Japanese cancer referral center from November 2019 to August 2021. We evaluated the results of CGP tests, treatments based on CGP tests, and survival time. Eight cases (6.9%) were diagnosed as tumor mutation burden-high (TMB-H) and/or microsatellite instability-high (MSI-H). The gene mutation rates of KRAS/TP53/CDKN2A/SMAD4 were 93.0/83.0/53.0/25.2%, respectively. Twenty-five patients (21.7%) had homologous recombination deficiency (HRD)-related genetic mutations. Four patients (3.5%) having TMB-H and/or MSI-H were treated with pembrolizumab, and only two patients (1.7%) participated in the clinical trials. Patient characteristics were not significantly different between patients with and without HRD-related gene mutations. The median OS was significantly longer in the HRD (+) group than in the HRD (−) group (749 days vs. 519 days, p = 0.047). In multivariate analysis, HRD-related gene mutation was an independent prognostic factor associated with favorable OS. CGP tests for patients with IPC have the potential utility of detecting HRD-related gene mutations as prognostic factors as well as a therapeutic search. [ABSTRACT FROM AUTHOR]

Introduction: Recently, a novel self-assembling peptide hemostatic gel has become available in Japan. However, the safety and efficacy of this novel self-assembling peptide hemostatic gel remain unclear for bleeding after EST. The aim of this study was to evaluate the safety and efficacy of a novel self-assembling peptide hemostatic gel for bleeding after EST, and to perform a comparison to a conventional endoscopic hemostasis technique. Method: This retrospective study was carried out between January 2019 and October 2022. Patients who developed bleeding associated with EST were enrolled. The patients were divided into two groups based on the hemostasis technique used: a conventional hemostasis technique (Group A) or a novel self-assembling peptide hemostatic gel hemostasis technique (Group B). Result: A total of 62 patients (Group A, n = 36; Group B, n = 26) were included. Endoscopic hemostasis was initially obtained in 72.2% (26/32) of patients in Group A and in 88.4% (23/26) of patients in Group B, which was not significantly different (p = 0.1320). However, the procedure time was significantly shorter in Group B (mean, 9.38 min) compared with Group A (mean, 15.4 min) (p = 0.0103). There were no significant differences in the severity of bleeding between the two groups (p = 0.4530). Post-EST bleeding was observed in six patients (Group A, n = 4; Group B, n = 2). Adverse events were more frequently observed in Group A (n = 12) than in Group B (n = 1) (p = 0.0457). Conclusions: PuraStat application for EST bleeding might be safe and effective, and is comparable to the conventional endoscopic hemostasis technique, although further prospective randomized trials are needed. [ABSTRACT FROM AUTHOR]

Simple Summary: In dogs, hundreds of hereditary diseases are currently known, representing a major health problem in small animal clinical practice. Hereditary gastrointestinal (GI) polyposis in Jack Russell Terriers (JRTs) is a hereditary disease recently discovered in Japan. This is an autosomal dominant disease caused by a germline variant in the adenomatous polyposis coli (APC) gene. Dogs with hereditary GI polyposis develop solitary and multiple tumors predominantly in the stomach and/or colorectum but have a much better prognosis than sporadic cases of GI tumors. Since the discovery of this disease, the number of newly diagnosed cases in Japan has increased, allowing the update of the disease's clinical and pathological features. In the present study, some patients exhibited more severe condition than previously reported, including cases harboring tumors in the small intestine besides the stomach and colorectum. In addition, the rare cases died from systemic metastasis of GI tumors. Our study would facilitate the accurate diagnosis of hereditary GI polyposis in JRTs and raise global awareness of this novel hereditary disease. Hereditary GI polyposis in JRTs is a novel hereditary disease characterized by the development of solitary and multiple polypoid tumors, predominantly in the stomach and/or colorectum. Our recent study indicated that JRTs with GI neoplastic polyps harbor an identical germline variant in the APC gene, c.[462_463delinsTT], in a heterozygous state. Unlike sporadic cases, dogs afflicted with hereditary GI polyposis can be expected to have a prolonged survival time, as hereditary tumors are noninvasive. Since the discovery of this disease, the number of newly diagnosed cases in Japan has increased, allowing us to update the clinical and pathological features and provide a large number of diagnostic images. The present clinical case series study employing various diagnostic imaging techniques revealed that some of the cases harbored tumors in the small intestine in addition to the stomach and colorectum. Moreover, although rare, hereditary GI cancers can progress to the advanced stage and develop systemic metastasis, similar to sporadic GI tumors. These findings indicate that there is a wider range of variation in disease severity than was initially recognized. Our results can contribute to the accurate diagnosis of hereditary GI polyposis in clinical practice, pathological examinations, and future research. [ABSTRACT FROM AUTHOR]

Intraductal papillary neoplasm of the bile duct (IPNB), a pre-invasive neoplasm of the bile duct, is being established pathologically as a precursor lesion of invasive cholangiocarcinoma (CCA), and at the time of surgical resection, approximately half of IPNBs show stromal invasion (IPNB associated with invasive carcinoma). IPNB can involve any part of the biliary tree. IPNB shows grossly visible, exophytic growth in a dilated bile duct lumen, with histologically villous/papillary neoplastic epithelia with tubular components covering fine fibrovascular stalks. Interestingly, IPNB can be classified into four subtypes (intestinal, gastric, pancreatobiliary and oncocytic), similar to intraductal papillary mucinous neoplasm of the pancreas (IPMN). IPNBs are classified into low-grade and high-grade based on lining epithelial features. The new subclassification of IPNB into types 1 (low-grade dysplasia and high-grade dysplasia with regular architecture) and 2 (high-grade dysplasia with irregular architecture) proposed by the Japan–Korea pathologist group may be useful in the clinical field. The outcome of post-operative IPNBs is more favorable in type 1 than type 2. Recent genetic studies using next-generation sequencing have demonstrated the existence of several groups of mutations of genes: (i) IPNB showing mutations in KRAS, GNAS and RNF43 belonged to type 1, particularly the intestinal subtype, similar to the mutation patterns of IPMN; (ii) IPNB showing mutations in CTNNB1 and lacking mutations in KRAS, GNAS and RNF43 belonged to the pancreatobiliary subtype but differed from IPMN. IPNB showing mutation of TP53, SMAD4 and PIK3CA might reflect complicated and other features characterizing type 2. The recent recognition of IPNBs may facilitate further clinical and basic studies of CCA with respect to the pre-invasive and early invasive stages. [ABSTRACT FROM AUTHOR]