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Kentaro Yamazaki

Publications and source records attributed to Kentaro Yamazaki.

At least 19 recordsLinked to original sources

Molecular Residual Disease and Recurrence in Rectal Cancer Patients Undergoing Upfront Surgery: A Prospective Cohort Study.

OBJECTIVE: To evaluate the prognostic utility of postoperative circulating tumor DNA (ctDNA) for recurrence and treatment response in patients with rectal cancer undergoing upfront surgery. BACKGROUND: ctDNA-based molecular residual disease (MRD) testing shows promise in colorectal cancer, but its role in patients with rectal cancer not receiving neoadjuvant therapy is unclear. This study evaluates whether postoperative ctDNA predicts disease-free survival (DFS) and guides adjuvant chemotherapy (ACT) decisions. METHODS: We analyzed ctDNA from patients with stage II to III rectal cancer (N=250) enrolled in the GALAXY study, a multicenter registry in Japan. A clinically validated, personalized, tumor-informed 16-plex PCR next-generation sequencing assay (Signatera) was used to detect and quantify ctDNA. The primary outcome was DFS, defined as the time from landmark to recurrence, death, or the latest radiologic assessment. RESULTS: In the MRD window (2-10&#xa0;wk postsurgery, before ACT), 14.2% (35/246) of patients were ctDNA-positive and had significantly shorter DFS (HR: 9.96, 95% CI: 5.76-17.2, P <0.0001). Among patients who were ctDNA-positive in the MRD window, a significant benefit from ACT was observed (HR: 0.28, 95% CI: 0.09-0.89, P =0.031), whereas no benefit was seen in ctDNA-negative patients (HR: 0.59, 95% CI: 0.26-1.35, P =0.211). When analyzing ctDNA dynamics from the MRD window to 6 months postsurgery, recurrence risk was higher in patients who converted from ctDNA-negative to positive (HR: 8.22, 95% CI: 1.86-36.32, P =0.0055) and who remained ctDNA-positive (HR: 45.48, 95% CI: 14.31-144.57, P <0.0001) compared with serially ctDNA-negative patients. CONCLUSIONS: Postoperative ctDNA status is a robust biomarker predicting recurrence risk and ACT benefit in patients with rectal cancer undergoing upfront surgery.

Humans↗

Presence of beta-linked GalNAc residues on N-glycans of human thyroglobulin.

Hepatic asialoglycoprotein receptor, which may mediate the clearance of circulating thyroglobulin, is known to have a high affinity for GalNAc. Recently, the receptor has been reported to be present also in the thyroid, implicating interaction with thyroglobulin. Here, mammalian thyroglobulins were analyzed for GalNAc termini by Western blotting with GalNAc-recognizing lectins labeled with peroxidase or (125)I. Wistaria floribunda lectin was found to bind human thyroglobulin and, to some extent, bovine, but not porcine thyroglobulin. After desialylation, the lectin bound all of the thyroglobulins tested. The binding was inhibited by competitive inhibitor GalNAc. Peptide N-glycanase treatment of human desialylated thyroglobulin resulted in the complete loss of reactivity with W. floribunda lectin, indicating that the binding sites are exclusively on N-glycans. The binding sites on human desialylated thyroglobulin were partly sensitive to beta-galactosidase, and the remainder was essentially sensitive to beta-N-acetylhexosaminidase. On the other hand, the binding sites of bovine and porcine desialylated thyroglobulins were totally sensitive to beta-galactosidase. Thus the lectin binds beta-Gal termini, as well as beta-GalNAc. GalNAc-specific Dolichos biflorus lectin also bound human thyroglobulin weakly. In contrast to W. floribunda lectin, desialylation diminished binding, suggesting that these two lectins recognize different GalNAc-terminated structures. Again, the binding was inhibited by GalNAc and by treatment with peptide N-glycanase. These results strongly indicate the presence of distinct GalNAc termini of N-glycans on human thyroglobulin.

Acetylgalactosamine↗

Potential effect on cellular response to cadmium of a single-nucleotide A --> G polymorphism in the promoter of the human gene for metallothionein IIA.

Most people generally ingest cadmium in their food. Cadmium that has accumulated in tissues induces the synthesis of metallothioneins (MTs) which are metal-binding proteins that bind tightly to cadmium to inhibit its renal toxicity. Individuals whose ability to induce the synthesis of MTs is low seem likely to be particularly susceptible to the toxic effects of cadmium. In this study, we analyzed the polymorphism of the promoter region of the gene for MT-IIA, the major species of MT in humans, in 119 adult Japanese subjects. We found that about 18% of the subjects had an A --> G single-nucleotide polymorphism in the core region of the promoter near the TATA box. A reporter-gene assay using HEK293 cells showed that replacement of A by G at position -5 reduced the efficiency of the cadmium-induced transcription of the gene for MT-IIA. This single-nucleotide polymorphism inhibited the binding of nuclear proteins to the core promoter region of the gene for MT-IIA. When the promoter region upstream of the TATA box was replaced by a sequence that contained three dioxin-responsive elements, the reporter-gene assay demonstrated that the A --> G single-nucleotide polymorphism resulted in a marked reduction in the rate of dioxin-induced transcription. These results suggest that the A --> G single-nucleotide polymorphism reduces the efficiency of those aspects of the transcription of the gene for MT-IIA that are controlled by general transcription factors.

Adult↗

Origin and evolution of gene for prolactin-induced protein.

Prolactin-induced protein (PIP) is a small protein secreted into the fluid in several glands. We determined the PIP coding sequences of 5 hominoid species and estimated the numbers of synonymous and nonsynonymous substitutions for each branch of the mammalian PIP gene tree. The branch connecting hominoids and Old World monkeys showed significantly higher nonsynonymous than synonymous substitutions. These changes tended to be accumulated in the fibronectin-binding domain. Many other primate branches also showed higher nonsynonymous than synonymous substitutions, thus suggesting that the PIP genes of primates have experienced some kind of positive selection. We also considered the phylogenetic relationship of the PIP gene with the alpha-2-macroglobulin gene family. The results indicate that the PIP gene arose by partial gene duplication from a member of the alpha-2-macroglobulin gene family after the divergence between amphibians and other tetrapods.

Amino Acid Sequence↗

Comparison between computed tomography (CT) and autopsy findings in cases of abdominal injury and disease.

We report 10 autopsy cases involving fatal pathological changes in abdominal organs, for which findings of computed tomography (CT) on admission or after death were compared with autopsy findings. Two of the cases were death due to natural causes and eight were death due to traffic accidents. From the findings at autopsy, the causes of death were considered to be rupture of an aortic aneurysm in one case, gastrointestinal bleeding due to gastric cancer in one case, retroperitoneal bleeding in two cases, laceration of the liver in three cases, and traumatic rupture of the small intestine in three cases. CT findings revealed ascites or retroperitoneal bleeding in eight cases. However, in the cases of small-intestinal rupture, CT findings on admission revealed no free air. Therefore, ascites on CT should be regarded as a useful indicator of blunt abdominal trauma. Hepatic portal venous gas, known to be a post-mortem change, was significantly evident on post-mortem CT in cases of traumatic liver or intestinal injury, and was also seen in cases where the period between the accident and CT examination was long.

Accidents, Traffic↗

Postmortem computed tomographic (PMCT) and postmortem magnetic resonance imaging (PMMRI) demonstration of fatal massive retroperitoneal hemorrhage caused by abdominal aortic aneurysm (AAA) rupture.

We report a case of fatal massive retroperitoneal hemorrhage caused by the rupture of an abdominal aortic aneurysm (AAA) in which postmortem computed tomography (PMCT) and postmortem magnetic resonance imaging (PMMRI) provided clear delineation. In this case, the autopsy imaging system using PMCT and PMMRI was useful as a screening method to determine the cause of death as AAA rupture and became a guide for the subsequent autopsy.

Aortic Aneurysm, Abdominal↗

Postmortem computed tomography for detecting causes of sudden death in infants and children: retrospective review of cases.

PURPOSE: The aim of this study was to investigate the usefulness of postmortem computed tomography (PMCT) in detecting causes of sudden death in infants and children. MATERIALS AND METHODS: Our subjects were 15 nontraumatically deceased patients (nine boys and six girls, ranging in age from 20 days after birth to 12 years old, mean age 1.6 years), who had been in a state of cardiopulmonary arrest on arrival at our hospital. PMCT was performed within 2 h after certification of death: head (15 cases), chest (11 cases), and abdomen (12 cases). Blood was collected from 11 of the patients at the time of cardiopulmonary resuscitation. An autopsy was conducted on two. RESULTS: PMCT did not show any traumatic changes indicating child abuse. It was difficult to presume the cause of death with PMCT alone, but the cause of death in 14 of 15 cases could be presumed by combining information from their medical history, clinical course before death, PMCT findings, laboratory data, and bacterial culture. The remaining subject was classified as cause unknown. CONCLUSION: The causes of sudden death in infants and children were detected at a high rate when we comprehensively investigated the PMCT and other examination findings.

Autopsy↗

[IFL].

An IFL regimen combining irinotecan, a bolus administration of 5-fluorouracil (5-FU) and leucovorin (LV) was associated with a significantly better response rate, progression-free survival and median overall survival, compared to 5-FU/LV against metastatic colorectal cancer. Despite a favorable initial report, randomized trials have suggested that triple therapy may be more toxic (severe neutropenia, diarrhea), leading to unacceptably high rates of early treatment-related mortality. On the other hand,a survival benefit for the oxaliplatin-containing regimen (FOLFOX 4) compared to bolus IFL, has been shown from INT trial 9741, and a European trial (V 308) suggests similar efficacy for combinations of irinotecan or oxaliplatin with short-term infusional 5-FU/LV (FOLFIRI or FOLFOX 6). Overall, FOLFIRI or FOLFOX regimen is now a standard option for first-line treatment of metastatic CRC.

Antineoplastic Combined Chemotherapy Protocols↗

Small cell carcinoma of the esophagus responding to fourth-line chemotherapy with weekly paclitaxel.

A patient was diagnosed with a small cell carcinoma of the esophagus (T4N1M1b by the International Union Against Cancer [UICC] classification) in October 2002, and initially received two courses of concurrent chemotherapy with 5-fluorouracil (5-FU; 400 mg/m(2) by continuous infusion; days 1-5 and 8-12) and cisplatin (40 mg/m(2) by drip infusion; days 1 and 8) and radiation therapy (2 Gy/day, days 1-5, 8-12, and 15-19; total, 30 Gy per course) with the second course given after a 2-week interval. Two courses of chemotherapy with 5-FU (800 mg/m(2); days 1-5) and cisplatin (80 mg/m(2); day 1) given after this was completed. Although a complete response had been confirmed, recurrence with multiple liver and lymph node metastases was detected 3 months after the cessation of the second course of chemotherapy. Although the patient received second-line chemotherapy with irinotecan (150 mg/m(2); every 2 weeks) from June 2003, the disease progressed. Brain metastases developed during third-line chemotherapy with gemcitabine (1000 mg/m(2) weekly by drip infusion). The symptoms were attenuated after whole-brain radiation (30 Gy), and fourth-line chemotherapy using paclitaxel (80 mg/m(2); weekly) was initiated from November 2003. A computed tomography scan 1 month after the first course of paclitaxel showed remarkable regression of the liver metastases. The treatment strategy used for treating small cell carcinomas of the lung may be applicable for these carcinomas of the esophagus.

Aged↗

Cardiovascular gas on non-traumatic postmortem computed tomography (PMCT): the influence of cardiopulmonary resuscitation.

PURPOSE: The purpose of this study was to investigate the causes of cardiovascular gas (CVG) detected on non-traumatic postmortem computed tomography (PMCT). MATERIALS AND METHODS: PMCT was performed on 247 subjects within two hours of non-traumatic death, including 228 patients who had undergone cardiopulmonary resuscitation (CPR) and 19 patients who had not. We evaluated the incidence and distribution of CVG in four areas of the heart, namely, 1) the upper course of the right atrium (UC-RA), 2) the right atrium, 3) the right ventricle, and 4) the left heart (left atrium, left ventricle, and aorta). RESULTS: CVG was observed in 163 (71%) of the 228 patients who underwent CPR. In those 163 patients, we detected CVG in the UC-RA (103 patients), right atrium (81 patients), right ventricle (94 patients), and left heart (5 patients). Nineteen patients who received no CPR showed no CVG. CONCLUSION: CVG on non-traumatic PMCT is mainly caused by CPR, which is characterized by venous catheterization that permits possible air inflow and by pneumatization of dissolved gas in the blood as a result of cardiac massage.

Adolescent↗

Postmortem magnetic resonance imaging (PMMRI) demonstration of reversible injury phase myocardium in a case of sudden death from acute coronary plaque change.

We report a case of sudden death from acute coronary plaque change in which postmortem magnetic resonance imaging (PMMRI) detected reversible injury phase myocardium. Postmortem computed tomography (PMCT) of the chest showed diffuse ground-glass attenuation (GGA) in both lungs, suggesting pulmonary edema due to cardiac pump failure. T2-weighted imaging (T2WI) of PMMRI delineated the left anterior descending coronary artery (LAD) territory as showing high signal intensity relative to the remaining myocardium. Therefore, we presumed the cause of death was myocardial infarction (MI) of the LAD territory. Autopsy showed acute plaque change in the LAD, however, there were no indications of MI. In this case, autopsy imaging using PMCT and PMMRI was useful as a guide for autopsy.

Autopsy↗

Non-traumatic postmortem computed tomographic (PMCT) findings of the lung.

PURPOSE: We attempted to obtain postmortem computed tomographic (PMCT) images of the lung in cases of non-traumatic death and describe the results to distinguish usual postmortem findings from those of specific thoracic causes of death. MATERIALS AND METHODS: Our subjects were a total of 150 consecutive non-traumatic cases with cardiopulmonary arrest on arrival who were examined by CT within 2h after certification of death between January 1993 and December 2001. PMCT images of the lung and the frequency of imaging findings (dependent density, ground glass attenuation (GGA), consolidation, pleural effusion, and endotracheal (or endobronchial) air defect) were retrospectively reviewed. Autopsy had been conducted in 16 of the cases. RESULTS: The causes of death and frequency percentages of dependent density, GGA, consolidation, pleural effusion, and endotracheal (or endobronchial) air defect were: 91 cases of acute heart failure (AHF) (69, 66, 24, 11, 14%), 23 cases of aortic dissection (57, 39, 4, 52, 0%), 11 cases of pneumonia (18, 82, 100, 45, 27%), 23 other specified cases (52, 30, 13, 17, 9%), and two unspecified cases (0, 0, 0, 50, 0%), [total respective frequency percentages were (60, 57, 25, 21, 12%)]. Autopsy confirmed that GGA on PMCT in AHF cases corresponded to pulmonary edema. CONCLUSION: When PMCT of the lung shows no other shadows than dependent density, further analysis is necessary to detect the cause of death.

Adolescent↗

Hepatic portal venous gas and hyper-dense aortic wall as postmortem computed tomography finding.

Postmortem computed tomography (PMCT) is useful for diagnosis of cause of death not only by emergency physicians but also medical examiners or police surgeons conducting postmortem studies. However, postmortem biological conditions are quite different from those in the living body. Hepatic portal venous gas (HPVG) and a hyperdense aortic wall (HDAW) are often found by PMCT, although no significant autopsy findings are evident in the liver or aorta. In this study we compared the findings of PMCT with those obtained at autopsy, and discussed the cause of these PMCT features. PMCT was conducted in 12 autopsy cases, comprising eight cases of natural death and four of unnatural death. HPVG was seen in five cases and HDAW in seven. In the cases showing HPVG, visceral abdominal injury, bowel distention or acute circulatory dysfunction was found at autopsy. In the cases showing HDAW, atherosclerosis or an increase in blood viscosity due to dehydration or postmortem changes was evident. Although the precise causes of these PMCT findings are not completely clear, the changes evident at autopsy provide some clues.

Adolescent↗