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418 result(s) for "Kato, Toshio"
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Diagnostic Potential of Cell-Free and Exosomal MicroRNAs in the Identification of Patients with High-Risk Colorectal Adenomas
Although there is a growing interest in developing circulating microRNA (miRNA) as noninvasive diagnostic biomarkers for the detection of high-risk colorectal adenomas and early-stage CRCs, but the comparative diagnostic significance of serum vs. exosomal miRNAs remains unexplored. Based upon published literature, we performed an initial discovery step by investigating the expression of a miRNA panel in 20 normal colonic mucosa, 27 adenomas, and 19 CRC tissues. We performed subsequent validation by quantifying expression of candidate miRNAs in total serum and in exosomes from 26 adenoma patients and 47 healthy controls, and evaluated their clinical significance and potential diagnostic value in colorectal adenomas. We observed that the expression of four miRNAs, miR-21, miR-29a, miR-92a, and miR-135b, was significantly higher in colorectal adenomas vs. normal colonic mucosa. During validation, expression of miR-21, miR-29a and miR-92a in serum was significantly higher in adenomas vs. healthy controls, significantly correlated with adenoma size and total adenoma number within the colorectum, and significantly discriminated patients with advanced adenomas. In contrast, although exosomal miR-21 and miR-29a levels in adenoma patients were significantly higher than those of healthy volunteers, only exosomal miR-21 significantly correlated with adenoma size and total adenoma number, and could discriminate patients with high-risk adenomas. Compared to exosomal miRNAs, serum levels of miR-21, miR-29a and miR-92a are superior diagnostic biomarkers in patients with high-risk adenomatous polyps.
Pathological complete response in microsatellite- stable gastric cancer with liver and bulky lymph node metastases after nivolumab-based chemotherapy and surgery: a case report
Gastric cancer with liver metastases is generally associated with poor prognosis, and curative treatment is rarely achieved. Recently, the combination of cytotoxic chemotherapy and immune checkpoint inhibitors (ICIs) has shown promise. However, the efficacy of ICIs in treating microsatellite-stable (MSS) gastric cancer remains controversial. Herein, we present a case of advanced MSS gastric cancer with liver and bulky lymph node metastases, in which combination therapy with S-1 plus oxaliplatin (SOX) and nivolumab led to a pathological complete response. A 64-year-old man was diagnosed with gastric adenocarcinoma with a solitary liver metastasis (S6) and bulky regional lymph node metastasis. Four cycles of SOX and nivolumab (360 mg every 3 weeks) were administered. Imaging revealed marked tumor regression, and surgery was performed. The patient underwent distal gastrectomy with D2 lymphadenectomy and partial hepatectomy. Pathological evaluation revealed complete tumor regression in the primary lesion, lymph nodes, and liver. The tumor was MSS, Epstein-Barr virus-negative and had a low tumor mutational burden (TMB). Immunohistochemistry showed a mean CD8+ tumor-infiltrating lymphocyte density of 59.5 ± 14.3 cells per high-power field, a programmed death-ligand 1 (PD-L1) combined positive score (CPS) of ≥ 70% (clone 28-8), and a germline TP53 p.R106C mutation. This case illustrates that even in MSS gastric cancer with low TMB levels, exceptionally high PD-L1 expression may predict a profound response to ICI-based therapy. The PD-L1 CPS may serve as a critical biomarker independent of TMB or microsatellite-instability status.
A Real-Time Near-Infrared Fluorescence Imaging Method for the Detection of Oral Cancers in Mice Using an Indocyanine Green–Labeled Podoplanin Antibody
Podoplanin is distinctively overexpressed in oral squamous cell carcinoma than oral benign neoplasms and plays a crucial role in the pathogenesis and metastasis of oral squamous cell carcinoma but its diagnostic application is quite limited. Here, we report a new near-infrared fluorescence imaging method using an indocyanine green (ICG)–labeled anti-podoplanin antibody and a desktop/a handheld ICG detection device for the visualization of oral squamous cell carcinoma–xenografted tumors in nude mice. Both near-infrared imaging methods using a desktop (in vivo imaging system: IVIS) and a handheld device (photodynamic eye: PDE) successfully detected oral squamous cell carcinoma tumors in nude mice in a podoplanin expression–dependent manner with comparable sensitivity. Of these 2 devices, only near-infrared imaging methods using a handheld device visualized oral squamous cell carcinoma xenografts in mice in real time. Furthermore, near-infrared imaging methods using the handheld device (PDE) could detect smaller podoplanin-positive oral squamous cell carcinoma tumors than a non-near-infrared, autofluorescence-based imaging method. Based on these results, a near-infrared imaging method using an ICG-labeled anti-podoplanin antibody and a handheld detection device (PDE) allows the sensitive, semiquantitative, and real-time imaging of oral squamous cell carcinoma tumors and therefore represents a useful tool for the detection and subsequent monitoring of malignant oral neoplasms in both preclinical and some clinical settings.
Identification of proteasomal catalytic subunit PSMA6 as a therapeutic target for lung cancer
To identify potential therapeutic targets for lung cancer, we performed semi‐genome‐wide shRNA screening combined with the utilization of genome‐wide expression and copy number data. shRNA screening targeting 5043 genes in NCI‐H460 identified 51 genes as candidates. Pathway analysis revealed that the 51 genes were enriched for the five pathways, including ribosome, proteasome, RNA polymerase, pyrimidine metabolism and spliceosome pathways. We focused on the proteasome pathway that involved six candidate genes because its activation has been demonstrated in diverse human malignancies, including lung cancer. Microarray expression and array CGH data showed that PSMA6, a proteasomal subunit of a 20S catalytic core complex, was highly expressed in lung cancer cell lines, with recurrent gene amplifications in some cases. Therefore, we further examined the roles of PSMA6 in lung cancer. Silencing of PSMA6 induced apoptosis or G2/M cell cycle arrest in cancer cell lines but not in an immortalized normal lung cell line. These results suggested that PSMA6 serves as an attractive target with a high therapeutic index for lung cancer. By doing an integrative analysis we have identified PSMA6, a subunit of the proteasome complex, as one of the most promising targets for lung cancer. We showed that PSMA6 knockdown suppressed the viability of cancer cells through the induction of apoptosis or cell cycle arrest at G2/M, with only a minimal effect on normal lung epithelial cells. Our data suggested that targeting PSMA6 for lung cancer may be an attractive novel therapeutic strategy.
Acute necrotizing calculous cholecystitis after treatment with ceftriaxone in an elderly patient: a case report
Background Ceftriaxone, a third-generation cephalosporin antibiotic with a long plasma half-life, is widely used to treat various infections. The use of ceftriaxone can sometimes induce biliary sludge or stone formation. Although most cases of ceftriaxone-induced pseudolithiasis are asymptomatic or mild and resolve with discontinuation of the drug, we experienced an elderly case of severe acute necrotizing calculous cholecystitis after administration of ceftriaxone. Case presentation A 72-year-old male patient was admitted to our hospital because of acute diverticulitis in ascending colon. Ceftriaxone was administered at a dose of 2 g/day for 6 days. Although he recovered after therapy, he was readmitted about 2 weeks later because of severe pain with rebound tenderness in the right upper quadrant. An abdominal imaging study revealed stones and sludge in the gallbladder that were not observed before starting ceftriaxone therapy. Therefore, antibiotic treatment with flomoxef 2 g/day was indicated. However, on the fifth day of readmission, the peritoneal irritation symptoms in the right upper quadrant worsened, and elevated inflammatory response and liver dysfunction were observed. Cholecystectomy was performed based on these findings. The resected inflamed gallbladder showed acute necrotizing cholecystitis with sand granular gallstones. A comparative analysis of the infrared spectroscopic pattern of the composition of gallstones collected during surgery with that of the ceftriaxone powder revealed that both have very similar infrared spectroscopic patterns. Conclusions Ceftriaxone-related pseudolithiasis is generally reversible and mainly observed in children. Here, we report a rare case of ceftriaxone-related acute necrotizing cholecystitis in an elderly patient. We confirmed that the stones in the gallbladder are composed of ceftriaxone. The older age, dehydration, fasting, and long-time bed rest during the administration of high-dose ceftriaxone were the potential risk factors for gallstone formation.
A case of acute inhalation injury caused by premeditated chlorine gas exposure
Chlorine is a toxic gas that causes severe inhalation injury. We report the case of a 43‐year‐old woman who inhaled chlorine gas generated by mixing household bleach and vinegar. She was referred to our hospital because she had developed respiratory failure. Chest computed tomography (CT) showed diffuse ground‐glass opacity and the tree‐in‐bud pattern. We diagnosed acute inhalation injury compatible with that due to chlorine gas exposure. Six days after admission, her respiratory symptoms and abnormal CT findings fully resolved without the use of bronchodilators or corticosteroids. This is the first report of a patient with acute inhalation injury caused by intentional chlorine gas exposure. It is considered that chlorine gas reached her respiratory tract and induced widespread injury from bronchioles to alveoli. Here, we describe a case of acute inhalation injury caused by chlorine gas exposure.
Elevated plasma and bile levels of corisin, a microbiota-derived proapoptotic peptide, in patients with severe acute cholangitis
Background Acute cholangitis is a severe, life-threatening infection of the biliary system that requires early diagnosis and treatment. The Tokyo Guidelines recommend a combination of clinical, laboratory, and imaging findings for diagnosis and severity assessment, but there are still challenges in identifying severe cases that need immediate intervention. The microbiota and its derived products have been implicated in the pathogenesis of acute cholangitis. Corisin is a microbiome-derived peptide that induces cell apoptosis, acute tissue injury, and inflammation. This study aimed to evaluate the potential of plasma and bile corisin as a biomarker of acute cholangitis. Methods Forty patients with acute cholangitis associated with choledocholithiasis or malignant disease were enrolled. Nine patients without acute cholangitis were used as controls. Corisin was measured by enzyme immunoassays in plasma and bile samples. Patients were classified into severe and non-severe groups. The associations of plasma and bile corisin with the clinical grade of acute cholangitis and other parameters were analyzed by univariate and multivariate regression analysis. Results Plasma and bile corisin levels were significantly higher in patients with acute cholangitis than in controls. Patients with severe acute cholangitis had significantly higher plasma and bile corisin levels than those with non-severe form of the disease. Bile corisin level was significantly correlated with markers of inflammation, coagulation, fibrinolysis, and renal function. Univariate analysis revealed a significant association of bile corisin but a weak association of plasma corisin with the clinical grade of acute cholangitis. In contrast, multivariate analysis showed a significant relationship between plasma corisin level and the disease clinical grade. The receiver operating characteristic curve analysis showed low sensitivity but high specificity for plasma and bile corisin to detect the severity of acute cholangitis. The plasma and bile corisin sensitivity was increased when serum C-reactive protein level was included in the receiver operating characteristic curve analysis. Conclusions Overall, these findings suggest that plasma and bile corisin levels may be useful biomarkers for diagnosing and monitoring acute cholangitis and that corisin may play a role in the pathophysiology of the disease by modulating inflammatory, coagulation and renal pathways.
Hangeshashinto-Associated Mesenteric Phlebosclerosis and Highly Atypical Adenoma Requiring Laparoscopic Right Hemicolectomy
Mesenteric phlebosclerosis is a rare ischemic colonic disorder caused by impaired venous drainage. Its prevalence is higher in East Asia, where herbal medicine is widely used. Treatment remains controversial. A 76-year-old woman who had taken Hangeshashinto, an herbal medicine, for 11 years was admitted for endoscopic treatment of high-grade dysplasia in the ascending colon. She had diarrhea and mesenteric phlebosclerosis diagnosed by abdominal computed tomography at age 71. At age 75, small polyps were detected in the ascending colon. A subsequent study revealed an increase in polyp size to 15 mm. Endoscopic mucosal resection failed to remove the lesion. A biopsy showed high-grade dysplasia with possible colon cancer risk. Conservative therapy did not improve mesenteric phlebosclerosis-related diarrhea; therefore, a laparoscopic right hemicolectomy was performed. Intraoperatively, the cecum was adherent to the abdominal wall and the right ovary. The specimen showed high-grade dysplasia in the mucosa and severe submucosal fibrosis. No metastasis was observed. This case shows the link between mesenteric phlebosclerosis and high-grade dysplasia in the ascending colon. Endoscopic mucosal resection was unsuccessful in removing the tumor. Endoscopic submucosal dissection was an alternative, but its safety in mesenteric phlebosclerosis-affected colonic segments remains uncertain. A laparoscopic right hemicolectomy was performed.
Bronchial carcinoid tumor managed with bronchial artery embolization before endobronchial resection: A case report
Endobronchial resection using a bronchoscope is often selected as treatment for carcinoid tumors located in the central airways. However, massive bleeding is one of the most serious complications during bronchoscopic surgery. Here, we report the case of a 77‐year‐old female with a typical carcinoid tumor located in the right truncus intermedius who underwent bronchial artery embolization (BAE) one day before endobronchial intervention using a flexible bronchoscope. The tumor was successfully resected without bleeding. BAE prior to endobronchial resection of carcinoid tumors may be useful for reducing the risk of bleeding. We report a female case with a typical carcinoid tumor. She underwent bronchial artery embolization (BAE) before endobronchial intervention using a flexible bronchoscope. BAE prior to endobronchial resection of carcinoid tumors is useful for reducing the risk of bleeding.
Improving the Prognosis of Pancreatic Cancer Through Early Detection: Protocol for a Prospective Observational Study
Background: Pancreatic cancer is associated with high mortality and its rates of detection are very low; as such, the disease is typically diagnosed at an advanced stage. A number of risk factors for pancreatic cancer have been reported and may be used to identify individuals at high risk for the development of this disease. Objective: The aim of this prospective, observational trial is to evaluate a scoring metric for systematic early detection of pancreatic cancer in Mie Prefecture, Japan. Methods: Eligible patients aged 20 years and older will be referred from participating clinics in the Tsu City area to the Faculty of Medicine, Gastroenterology, and Hepatology at Mie University Graduate School, until September 30, 2022. Participants will undergo a detailed examination for pancreatic cancer. Data collection will include diagnostic and follow-up imaging data and disease staging information. Results: The study was initiated in September 2020 and aims to recruit at least 150 patients in a 2-year period. Recruitment of patients is currently still underway. Final data analysis is expected to be complete by March 2025. Conclusions: This study will provide insights into the feasibility of using a scoring system for the early detection of pancreatic cancer, thus potentially improving the survival outcomes of diagnosed patients. Trial Registration: UMIN-CTR Clinical Trials Registry UMIN000041624; https://tinyurl.com/94tbbn3s International Registered Report Identifier (IRRID): DERR1-10.2196/26898