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Background/Aim: The microRNA miR-452-5p holds a critical role in the progression of multiple tumor formations, but there is limited understanding regarding the epithelial-mesenchymal transition (EMT) progression and its underlying mechanisms in the early-stage colorectal cancer (CRC). We aimed to explore the change in miRNA expression in early-stage CRC and examine the role of these miRNAs in CRC. Materials and Methods: The expression levels of miR452-5p in tissues and cells of early-stage CRC were determined by real-time quantitative polymerase chain reaction. Additionally, the biological effects of miR-452-5p on CRC were investigated by in vitro functional experiments. Results: The expression levels of miR-452-5p were found increased in early-stage CRC tissue. We found that miR-452- 5p promoted CRC cell proliferation but inhibited epithelial– mesenchymal transition. Furthermore, miR-452-5p promoted cell proliferation through activation of the extracellular signal-regulated kinase pathway, and inhibited cell invasion through suppression of Slug (Snail2) expression and upregulation of E-cadherin expression. Conclusion: The expression of miR-452-5p is up-regulated in early CRC and suppresses epithelial–mesenchymal transition in CRC. These discoveries suggest that miR-452-5p has the potential to serve as a viable therapeutic target for CRC. [ABSTRACT FROM AUTHOR]

Aim: We analyzed the association between the modified albumin–bilirubin (mALBI) grade and therapeutic efficacy of atezolizumab plus bevacizumab (Atezo+Bev) for the treatment of unresectable hepatocellular carcinoma (u‐HCC). Methods: In this retrospective observational study, we included 71 u‐HCC patients treated with Atezo+Bev between September 2020 and September 2021. Patients were grouped corresponding to the mALBI grade at the start of treatment (mALBI 1+2a or mALBI 2b+3) and analyzed for therapeutic effect and the transition rate to secondary treatment. Results: According to the Response Evaluation Criteria in Solid Tumors, the overall response rate was significantly higher for the mALBI 1+2a group, than for the mALBI 2b+3 group, with 26.2% and 3.4%, respectively. The progression‐free survival (PFS) was significantly longer in the mALBI 1+2a group (10.5 months) than in the mALBI 2b+3 group (3.0 months). In the multivariate analysis, an mALBI of 1+2a was found to be an independent factor of PFS. The rate of second‐line treatment with multi‐targeted agents was also significantly higher in the mALBI 1+2a group. Conclusions: In real‐world practice, Atezo+Bev treatment might have higher therapeutic efficacy in u‐HCC patients with mALBI 1+2a. [ABSTRACT FROM AUTHOR]

Lenvatinib is a tyrosine kinase receptor inhibitor used to treat unresectable hepatocellular carcinoma (HCC). In this study, we investigated the antitumor effects of Lenvatinib treatment on HCC cell lines. Proliferation was examined in four HCC cell lines (HuH-7, Hep3B, Li-7, and PLC/PRF/5) using Cell Counting Kit-8 assays. Xenograft mouse models were used to assess the effects of Lenvatinib in vivo. Cell cycle, western blotting, and microRNA (miRNA) expression analyses were performed to identify the antitumor inhibitory potential of Lenvatinib on HCC cells. Lenvatinib treatment suppressed proliferation of HuH-7 and Hep3B, but not Li-7 and PLC/PRF/5 cells and induced G0/G1 cell cycle arrest and cyclin D1 downregulation in Lenvatinib-sensitive cells. Lenvatinib treatment also reduced tumor growth in HuH-7 xenograft mouse models. miRNA microarrays revealed that Lenvatinib treatment altered the expression of miRNAs in HuH7 cells and exosomes. Our results demonstrated the therapeutic potential of Lenvatinib and provide molecular mechanistic insights into its antitumor effects for treating HCC. [ABSTRACT FROM AUTHOR]

Background/Aim: Gemcitabine, an inhibitor of DNA synthesis, is the gold standard chemotherapeutic agent for pancreatic ductal adenocarcinoma (PDAC). MicroRNAs (miRNAs) play critical roles in cancers, including PDAC. However, less is known about the effect of gemcitabine on PDAC cells and miRNA expression in PDAC. We evaluated the effect of gemcitabine on the cell cycle of PDAC cells in vitro and in vivo and on the miRNA expression profile. Materials and Methods: Effects of gemcitabine on PK-1 and PK-9 cell growth were evaluated using a cell counting kit-8 assay. Xenografted mouse models were used to assess gemcitabine effects in vivo. Results: Gemcitabine inhibited the proliferation and tumour growth of PK-1 cells, and induced S phase cell cycle arrest. Numerous miRNAs were altered upon gemcitabine treatment of PK-1 cells and xenograft models. Conclusion: Altered miRNAs may serve as potential therapeutic targets for improving the efficacy of gemcitabine in PDAC. [ABSTRACT FROM AUTHOR]

Hepatitis B virus (HBV)-related hepatocarcinogenesis is not necessarily associated with the liver fibrotic stage and is occasionally seen at early fibrotic stages. MicroRNAs (miRNAs) are essentially 18- to 22-nucleotide-long endogenous noncoding RNAs. Aberrant miRNA expression is a common feature of various human cancers. The aberrant expression of specific miRNAs has been shown in hepatocellular carcinoma (HCC) tissue compared with nontumor tissue. Thus, we examined targetable miRNAs as a potential new biomarker related to the high risk of HBV-related hepatocarcinogenesis, toward the prevention of cancerrelated deaths. HCC tissue samples from 29 patients who underwent hepatectomy at our hospital in 2002-2013 were obtained. We extracted the total RNA and analyzed it by microRNA array, real-time RT-PCR, and three comparisons: 1) HBV-related HCC and adjacent nontumor tissue, 2) HCV-related HCC and adjacent nontumor tissue, and 3) non-HBV-, non-HCV-related HCC and adjacent nontumor tissue. We also performed a functional analysis of miRNAs specific for HBV-related HCC by using HBV-positive HCC cell lines. MiR- 210-3p expression was significantly increased only in the HBVrelated HCC tissue samples. MiR-210-3p expression was upregulated, and the levels of its target genes were reduced in the HBV-positive HCC cells. The inhibition of miR-210-3p enhanced its target gene expression in the HBV-positive HCC cells. In addition, miR-210-3p regulated the HBx expression in HBV-infected Huh7/NTCP cells. The enhanced expression of miR-210-3p was detected specifically in HBV-related HCC and regulated various target genes, including HBx in the HBV-positive HCC cells. MiR-210-3p might, thus, be a new biomarker for the risk of HBV-related HCC. NEW & NOTEWORTHY Our present study demonstrated that miR- 210-3p is the only microRNA with enhanced expression in HBV-related HCC, and the enhanced expression of miR-210-3p upregulates HBx expression. Therefore, miR-210-3p might be a pivotal biomarker of HBV-related hepatocarcinogenesis, and the inhibition of miR-210-3p could prevent inducing hepatocarcinogenesis related to HBV infection. [ABSTRACT FROM AUTHOR]

Fulminant hepatitis is a severe liver disease resulting in hepatocyte necrosis. Galectin-9 (Gal-9) is a tandem-repeat-type galectin that has been evaluated as a potential therapeutic agent for various diseases that regulate the host immune system. Concanavalin A (ConA) injection into mice results in serious, immune-mediated liver injury similar to human viral, autoimmune and fulminant hepatitis. The present study investigated the effects of Gal-9 treatment on fulminant hepatitis in vivo and the effect on the expression of microRNAs (miRNAs), in order to identify specific miRNAs associated with the immune effects of Gal-9. A ConA-induced mouse hepatitis model was used to investigate the effects of Gal-9 treatment on overall survival rates, liver enzymes, histopathology and miRNA expression levels. Histological analyses, TUNEL assay, immunohistochemistry and miRNA expression characterization, were used to investigate the degree of necrosis, fibrosis, apoptosis and infiltration of neutrophils and macrophages. Overall survival rates following ConA administration were significantly higher in Gal-9-treated mice compared with control mice treated with ConA + PBS. Histological examination revealed that Gal-9 attenuated hepatocellular damage, reduced local neutrophil infiltration and prevented the local accumulation of macrophages and liver cell apoptosis in ConA-treated mice. In addition, various miRNAs induced by Gal-9 may contribute to its anti-apoptotic, anti-inflammatory and pro-proliferative effects on hepatocytes. The results of the present study demonstrate that Gal-9 may be a candidate therapeutic target for the treatment of fulminant hepatitis. [ABSTRACT FROM AUTHOR]

Background: Ten to forty percent of nonalcoholic steatohepatitis (NASH) and HCV-related chronic liver disease (CLD-C) patients have antinuclear antibodies (ANAs). However, the relationship between autoimmune response and insulin resistance remains uncertain among those patients. The primary purpose of this study was to investigate whether or not ANA status was associated with the development of insulin resistance and obesity in NASH and CLD-C patients. Methods: Degrees of hepatic fibrosis and steatosis were evaluated by the classification proposed by Brunt et al. Obesity and insulin resistance were estimated by calculating body mass index and the value of homeostasis model of for assessment of insulin resistance (HOMA-IR), respectively. A revised scoring system was applied to the diagnosis of autoimmune hepatitis (AIH). Serum B-lymphocyte activating factor (BAFF) levels were determined, using an ELISA technique. Results: Ten of 25 (40%) NASH patients and 9 of 22 (41%) CLD-C patients had ANAs, though the titers were weak in most patients. Only one NASH patient met the category of “definite” AIH among the enrolled patients. Serum IgG levels were significantly higher in NASH and CLD-C patients with ANAs than in those without ANAs, and NASH and CLD-C patients with ANAs had significantly higher HOMA-IR values than those without ANAs (6.81 ± 3.36 vs. 4.00 ± 2.57, p = 0.0305, 3.01 ± 1.31 vs. 1.28 ± 0.50, p = 0.0011). CLD-C patients with ANAs had more advanced hepatic fibrosis and steatosis than those without ANAs, while ANA status was not associated with hepatic fibrosis or steatosis in NASH patients. Obesity was independent of ANA status in both subjects. Serum BAFF levels were significantly higher in CLD-C patients with ANAs than those in CLD-C patients without ANAs (1303 ± 268 vs. 714 ± 143 pg/ml, p = 0.0036). A close correlation between serum BAFF level and the HOMA-IR value was observed in CLD-C patients (r = 0.467, p = 0.0485). Conclusion: Our data suggest that NASH and CLD-C patients with ANAs have more severe insulin resistance than those without ANAs. More advanced insulin resistance deriving from excessive BAFF production may result in severe hepatic fibrosis and steatosis in CLD-C patients with ANAs. [ABSTRACT FROM AUTHOR]

A 72-year-old female was referred for further evaluation of epigastralgia. Abdominal contrast computed tomography revealed numerous tumors in the two lobes of the liver. Liver biopsy and immunohistochemical staining revealed that the tumor cells were positive for factor VIII-associated antigen, platelet endothelial cell adhesion molecule 1 and human hematopoietic progenitor cell antigen, concordant with a diagnosis of hepatic epithelioid hemangioendothelioma (HEH). To elucidate the etiology of HEH, particularly the microRNA (miRNA) profiles, tissue samples obtained from normal and tumor tissues were analyzed using a miRNA array system. A total of 14 miRNAs were significantly upregulated and 93 miRNAs were downregulated in the tumor tissues (P<0.01). Additionally, unsupervised hierarchical clustering analysis using Pearson's correlation revealed that the tumor tissues clustered separately from the normal tissues. The miRNA expression profile was analyzed in HEH and compared with angiosarcoma, which exhibits histology similar to HEH. Out of a total of 107 miRNAs, only miR-122-5p and miR-1290 demonstrated a differential expression pattern in angiosarcoma. Therefore, these miRNAs may be novel biological markers for the determination of a diagnosis of HEH in primary mesenchymal tumors of the liver. To the best of our knowledge, this study is the first report of a miRNA microarray analysis in HEH. [ABSTRACT FROM AUTHOR]

Dysregulation of apoptosis is a major hallmark in cancer biology that might equip tumors with a higher malignant potential and chemoresistance. The anti-cancer activities of lectin, defined as a carbohydrate-binding protein that is not an enzyme or antibody, have been investigated for over a century. Recently, galectin-9, which has two distinct carbohydrate recognition domains connected by a linker peptide, was noted to induce apoptosis in thymocytes and immune cells. The apoptosis of these cells contributes to the development and regulation of acquired immunity. Furthermore, human recombinant galectin-9, hG9NC (null), which lacks an entire region of the linker peptide, was designed to resist proteolysis. The hG9NC (null) has demonstrated anti-cancer activities, including inducing apoptosis in hematological, dermatological and gastrointestinal malignancies. In this review, the molecular characteristics, history and apoptosis-inducing potential of galectin-9 are described. [ABSTRACT FROM AUTHOR]

Hepatocellular carcinoma (HCC) is one of the most common causes of cancer-associated mortality worldwide. Although surgery is considered the most effective treatment for patients with HCC, its indication is restricted by limited criteria and a high relapse rate following surgery; therefore, systemic chemotherapy is required for patients with advanced-stage HCC to prolong their survival. MicroRNAs (miRNAs) are endogenous non-coding RNAs of 18-22 nucleotides in length. It has been reported that aberrant expression of miRNAs is a feature shared by various types of human cancer. Previous studies have indicated that the modulation of non-coding RNAs, particularly miRNAs, may be a valuable therapeutic target for HCC. The aim of the present study was to elucidate the miRNA profiles associated with differentiation and hepatitis B virus (HBV) infection observed in HCC cell lines. The human Alex, Hep3B, HepG2, HuH1, HuH7, JHH1, JHH2, JHH5, JHH6, HLE, HLF and Li-7 HCC cell lines were used for an miRNA array. Replicate data were analyzed following their classification into: i) Poorly- and well-differentiated human HCC cells and ii) HBV-positive and -negative human HCC cells. Out of the 1,719 miRNAs, 4 were found to be significantly upregulated and 52 significantly downregulated in the poorly-differentiated cells, as compared with the well-differentiated cells. Conversely, in the HBV-positive cells 125 miRNAs were found to be upregulated and 2 downregulated, as compared with the HBV-negative cells. Unsupervised hierarchical clustering analysis with Pearson's correlation revealed that the miRNA expression levels were clustered both together and separately in each group. In conclusion, miRNA profile characterization based on various parameters may be a novel approach to determine the etiology of HCC. [ABSTRACT FROM AUTHOR]

Percutaneous radiofrequency ablation (RFA) enables cauterization of liver cancer in a limited number of sessions without major complications. In contrast to the efficacy of this technique, the size of coagulation necrosis is limited due to increased impedance. D-sorbitol has been used as an irrigating fluid during transurethral resection of the prostate, since it is considered to be a dielectric fluid. In order to determine whether D-sorbitol enhances the effect of RFA, RFA was performed by slowly injecting 3% D-sorbitol near the tip of the RFA needle. The maximum of the total injected volume of D-sorbitol was 20 ml and RFA was terminated if the threshold of impedance was exceeded. RFA and D-sorbitol RFA were performed in 5 different parts of pig livers and dog livers in vivo. The total volumes of coagulation necrosis in the D-sorbitol RFA group were significantly higher compared with those in the RFA group. The total delivered energy in the D-sorbitol RFA group was also higher compared with that in the RFA group, due to the suppression of impedance elevation. No significant complications, such as bleeding or damage, were observed during the D-sorbitol RFA procedure in the in vivo model. In conclusion, RFA combined with D-sorbitol increases the total volume of coagulation necrosis through controlling impedance in the ablated liver and, therefore, D-sorbitol may be useful for the treatment of liver cancers. [ABSTRACT FROM AUTHOR]

Tissue sampling of primary duodenal lymphoma is essential for its histological diagnosis. Endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA), which is frequently used for submucosal tumor (SMT)-like duodenal tumors, is adequate for cytological diagnosis, but not for histological diagnosis. Therefore, in the present study, a mucosal incision-assisted biopsy (MIAB) was performed in an 81-year-old woman for the diagnosis of an SMT-like duodenal mass, as tissue sampling for histological analysis using a regular endoscopic biopsy had failed to establish a definite diagnosis of malignant lymphoma. EUS-FNA had also led to poor tissue sampling due to the difficult location of the duodenal tumor. The pathological examination of biopsy samples using MIAB revealed the presence of a diffuse proliferation of atypical lymphocytes, and the expression of cluster of differentiation (CD)20 and CD79a, but no expression of CD3 in the tumor specimens. The patient was diagnosed with diffuse large B-cell lymphoma. To the best of knowledge, this is first report of a case using MIAB as a sampling method for the histological diagnosis of SMT-like primary duodenal lymphoma. This case suggests that MIAB may be an essential method for obtaining tissue samples from SMT-like duodenal tumors. [ABSTRACT FROM AUTHOR]

Although the macroscopic characteristics of submucosal tumors (SMTs), such as gastrointestinal stromal tumors (GISTs), have been characterized, the assessment of SMTs by their endoscopically visualized features (EVF; which are observed by endoscopic imaging under direct view) remains unevaluated. The aim of the present study was to investigate the potential of endoscopic diagnostics for SMTs using EVF. The EVF of 26 gastric SMT cases, in which the final pathological diagnosis was obtained by core biopsy using the submucosal endoscopy with mucosal flap method, were retrospectively reviewed. Each type of SMT was classified according to the following five EVF: Color, clarity, shape, tumor coating and solidity. Additionally, the EVF of 13 low-risk GISTs and 13 benign submucosal tumors (BSTs) were comparatively evaluated for the five abovementioned EVF. Similar trends were identified between the low-risk GISTs, granular cell tumors and the schwannoma with regard to EVF. However, while these tumors exhibited cloudy EVF, the leiomyomas tended to exhibit clear EVF. Among SMTs of the heterotopic pancreas type, the EVF demonstrated particularly small nodules of the pancreatic tissue itself. Although the sample size included in the present study is small, a classification system for gastric SMTs was proposed according to the EVF. When compared with the BST group, the GIST group demonstrated a significantly higher frequency of tumors that exhibited a combination of three EVF (white, cloudy and rigid) that are consistent with all gastric GISTs (P<0.05). Gastric SMTs may be classified based on the EVF, which indicates that the EVF possess potential diagnostic value for the differentiation of GISTs from BSTs. [ABSTRACT FROM AUTHOR]

Percutaneous ethanol injection therapy (PEIT) has been administered as a safe therapeutic modality for patients with small hepatocellular carcinoma (HCC). Due to the nature of the straight approaching line of a PEIT or radiofrequency ablation needle, penetrating the vessels that are interposed between the dermal insertion point and the nodule is unavoidable. A device with an overcoat needle and coaxial curved PEIT needle was created that facilitated a detour around interposing large vessels in order to avoid unnecessary harmful effects that result from the PEIT procedure. Two cases of HCC located adjacent to a neighboring large vessel were treated with a curved PEIT needle. The curved PEIT needle, which is connected to an outer needle, enabled deviation around the interposing vessels and successful connection with the HCC. Careful use of the curved line of the PEIT needle enabled the safe and successful performance of the PEIT without any requirement for specific training. This hand-assisted technique may be an applicable treatment for small HCC located beneath large vessels as a direct therapeutic method using ultrasound guidance. [ABSTRACT FROM AUTHOR]

Advances in endoscopic submucosal dissection include a submucosal tunneling technique, involving the introduction of tunnels into the submucosa. These tunnels permit safer offset entry into the peritoneal cavity for natural orifice transluminal endoscopic surgery. Technical advantages include the visual identification of the layers of the gut, blood vessels, and subepithelial tumors. The creation of a mucosal flap that minimizes air and fluid leakage into the extraluminal cavity can enhance the safety and efficacy of surgery. This submucosal tunneling technique was adapted for esophageal myotomy, culminating in its application to patients with achalasia. This method, known as per oral endoscopic myotomy, has opened up the new discipline of submucosal endoscopic surgery. Other clinical applications of the submucosal tunneling technique include its use in the removal of gastrointestinal subepithelial tumors and endomicroscopy for the diagnosis of functional and motility disorders. This review suggests that the submucosal tunneling technique, involving a mucosal safety flap, can have potential values for future endoscopic developments. [ABSTRACT FROM AUTHOR]

Endoscopic submucosal dissection (ESD) is accepted as a minimally invasive treatment for colorectal cancer. However, due to technical difficulties and an increased rate of complications, ESD is not widely used in the colorectum. In some cases, endoscopic treatment alone is insufficient for disease control, and laparoscopic surgery is required. The combination of laparoscopic surgery and endoscopic resection represents a new frontier in cancer treatment. Recent developments in advanced polypectomy and minimally invasive surgical techniques will enable surgeons and endoscopists to challenge current practice in colorectal cancer treatment. Endoscopic full-thickness resection (EFTR) of the colon offers the potential to decrease the postoperative morbidity and mortality associated with segmental colectomy while enhancing the diagnostic yield compared to current endoscopic techniques. However, closure is necessary after EFTR and natural transluminal endoscopic surgery (NOTES). Innovative methods and new devices for EFTR and suturing are being developed and may potentially change traditional paradigms to achieve minimally invasive surgery for colorectal cancer. The present paper aims to discuss the complementary role of ESD and the future development of EFTR. We focus on the possibility of achieving EFTR using the ESD method and closing devices. [ABSTRACT FROM AUTHOR]

Endoscopic submucosal dissection (ESD) for upper gastrointestinal (GI) subepithelial tumors (SETs) originating in the muscularis propria (MP) layer is associated with numerous issues regarding secure closure and measures against accidental perforation. However, symptomatic benign GISETs or carcinoid tumors originating in the submucosa(SM) may be safely resected en-bloc using ESD. In this study, the feasibility and safety of ESD as a novel method for endoscopic resection for such GISETs revealed on endoscopic ultrasonography (EUS) was investigated. A total of 12consecutive cases of patients with symptomatic benign SETs (n=3; 1esophageal hemangioma and 2gastric lipomas) or small carcinoid tumors (n=9; <10mm, with an extremely low risk of metastasis) originating in the SM as determined on EUS, between March, 2009 and April, 2013, were retrospectively reviewed. The lesions were resected by ESD after confirming that the tumors originated from the SM. The complication rate following en-bloc resection was also determined. En-bloc resection was achieved in all 12 cases, the mean procedure time was 45 min (range, 20-120min) and no complications occurred intra- or postoperatively. There was no tumor recurrence or disease-related mortality reported during the follow-up period (median follow-up time, 13.4months). Histopathological curative resection was achieved with ESD without complications in all 9cases with carcinoid tumors. Therefore, if EUS reveals a SET originating in the SM without infiltration of the MP and resection is indicated due to the presence of abdominal symptoms, ESD may be a feasible option for diagnostic treatment with minimal invasiveness. However, larger-scale prospective studies are required to establish the feasibility and safety of this procedure. [ABSTRACT FROM AUTHOR]

Background: CD36, a class B scavenger receptor, participates in the pathogenesis of metabolic dysregulation such as insulin resistance, hepatic steatosis, and atherosclerosis. Persistent hepatitis C virus (HCV) infection often evokes these metabolic abnormalities. The primary purpose of this study was to investigate the role of CD36 in the pathogenesis of insulin resistance and hepatic steatosis caused by chronic HCV infection. Methods: Forty-five patients with HCV-related chronic liver disease (CLD-C) were enrolled in this study. CD36 expression in the liver specimen was examined by an immunohistochemical procedure. The concentrations of circulating soluble form of CD36 (sCD36) and oxLDL were determined by the enzyme-linked innunosorbent assay. Insulin resistance was estimated by the values of HOMA-IR. Results: Moderate to extensive hepatic CD36 expression was observed in the sinusoids of all enrolled CLD-C patients. CD36-positive sinusoids appeared to be identical to Kupffer cells. The severity of CD36 expression in the hepatic sinusoids was significantly correlated with the sCD36 level in sera of patients with CLD-C. The serum sCD36 levels were significantly correlated with body mass index and serum oxLDL levels in those patients. However, the serum sCD36 concentrations were independent of the values of HOMA-IR and the severity of hepatic steatosis. Conclusions: These data suggest that the serum sCD36 levels reflect the severity of CD36 expression on the Kupffer cells in patients with CLD-C, and that the serum sCD36 levels were associated with obesity, although the levels were independent of insulin resistance and hepatic steatosis in those patients. [ABSTRACT FROM AUTHOR]

Introduction Galectin-9 ameliorates various inflammatory conditions including autoimmune diseases by regulating T cell and macrophage/dendritic cell (DC) functions. However, the effect of galectin-9 on polymicrobial sepsis has not been assessed. Methods We induced polymicrobial sepsis by cecal ligation and puncture (CLP) in mice. The survival rate was compared between galectin-9- and PBS-treated CLP mice. An ELISA was used to compare the levels of various cytokines in the plasma and culture supernatants. Fluorescence-activated cell sorting analysis was further performed to compare the frequencies of subpopulations of spleen cells. Results Galectin-9 exhibited a protective effect in polymicrobial sepsis as demonstrated in galetin-9 transgenic mice and therapeutic galectin-9 administration. In contrast, such effect was not observed in nude mice, indicating the involvement of T cells in galectin-9-mediated survival prolongation. Galectin-9 decreased TNFα, IL-6, IL-10 and, high mobility group box 1 (HMGB1) and increased IL-15 and IL-17 plasma and spleen levels. Galectin-9 increased the frequencies of natural killer T (NKT) cells and PDCA-1+ CD11c+ macrophages (pDC-like macrophages) but did not change the frequency of CD4 or CD8 T cells, …T cells or conventional DC. As expected, galectin-9 decreased the frequency of Tim-3+ CD4 T cells, most likely Th1 and Th17 cells. Intriguingly, many spleen NK1.1+ NKT cells and pDC-like macrophages expressed Tim-3. Galectin-9 increased the frequency of Tim-3-expressing NK1.1+ NKT cells and pDC-like macrophages. Galectin-9 further increased IL-17+ NK1.1 + NKT cells. Conclusion These data suggest that galectin-9 exerts therapeutic effects on polymicrobial sepsis, possibly by expanding NKT cells and pDC-like macrophages and by modulating the production of early and late proinflammatory cytokines. [ABSTRACT FROM AUTHOR]

We herein present a case of an 87-year-old patient with multiple liver tumors identified on abdominal ultrasound. The assessment performed on admission included physical examination, computed tomography (CT) during hepatic angiography and CT during arterial portography. The examination revealed contrast enhancement of a proportion of the liver tumors (20 mm maximum diameter) during the arterial phase and mild contrast washout of those tumors during the delayed phase. On contrast-enhanced magnetic resonance imaging using gadolinium ethoxybenzyl diethylenetriamine pentaacetic acid, certain liver tumors exhibited contrast enhancement during the early phase and contrast washout during the hepatocyte phase in both lobes. By contrast, no lesions were identified during positron emission tomography imaging of the liver. A liver biopsy was performed and immunohistochemical staining revealed enhanced expression of cytokeratin AE1-AE3, synaptophysin, chromogranin A and CD56 and no expression of hepatocyte antigen or CΚ7. The mindbomb E3 ubiquitin protein ligase-1 index was ~2% in most of the tumor. The liver tumors were finally diagnosed as multiple intrahepatic metastases from a primary hepatic neuroendocrine tumor (PHNET). The patient underwent transarterial chemoembolisation with a combination of miriplatin (84 mg) mixed with gelatin sponge particles and lipiodol. To the best of our knowledge, this is the first report of PHNET in an patient aged >85 years. [ABSTRACT FROM AUTHOR]

Linitis plastica is a gastric cancer of diffuse histotype that presents in the fundic gland area, and is characterized by thickening of the stomach wall and deformation of the stomach, resulting in a leather bottle-like appearance. A 66-year-old female was admitted to Kagawa University Hospital (Kagawa, Japan) with epigastric pain. X-ray examination revealed reduced gastric distension and deformation of the stomach, which exhibited a leather bottle-like appearance. Endoscopy indicated a depressed lesion in the gastric antrum, and abnormal folds, which crossed to form a waffle-like appearance in the upper gastric body. Analysis of biopsy specimens from the depressed lesion revealed a poorly differentiated adenocarcinoma. Morphological changes in the gastric folds indicated that the tumor had invaded the upper gastric body, therefore, a total gastrectomy was performed. Subsequent pathological findings demonstrated that the tumor had spread from the primary lesion to the upper gastric body. Therefore, the present report recommends that the diagnosis of the spread of linitis plastica-type gastric cancer should include assessments of the primary lesion, as well as evaluation of morphological changes in the gastric folds. [ABSTRACT FROM AUTHOR]

The article focuses on the use of submucosal endoscopy with mucosal flap (SEMF) method and bloc biopsy in submucosal tumor diagnosis. It notes the advantage of SEMF method in the assessment of submucosal tumors' macroscopic characteristics. The major steps of bloc biopsy using the SEMF method are also discussed.