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Ken Yamaguchi

Publications and source records attributed to Ken Yamaguchi.

At least 19 recordsLinked to original sources
PubMed2026

Tumor Mutational Concordance and Recurrence Timing in Hepatocellular Carcinoma.

INTRODUCTION: In hepatocellular carcinoma (HCC), intrahepatic recurrence includes true recurrence from clonal relapse and multicentric recurrence from de novo tumorigenesis. Recurrence timing is used to distinguish these types; however, its accuracy remains unclear. This study aimed to classify recurrent tumors based on somatic mutational concordance and assess the validity of recurrence timing. METHODS: Whole-exome sequencing was performed on paired primary and recurrent HCC tumors from 49 patients enrolled in a prospective institutional omics project. Tumors with &#x2265; 10 shared somatic mutations were classified as true recurrence. Clinicopathological features, recurrence timing, driver mutation patterns, and survival outcomes were compared between recurrence types. Mutational concordance was quantified using shared variant counts and the Jaccard similarity index. RESULTS: Of the 49 patients, 22 (44.9%) showed true recurrence and 27 (55.1%) had multicentric recurrence. Multicentric recurrence tumors harbored no shared variants or only a single shared variant with the primary tumor. True recurrence was associated with significantly higher concordance in histological differentiation and Edmondson-Steiner grading and greater retention of CTNNB1, TP53, ARID1A, and KEAP1 mutations. The number of shared variants (median: 115 vs. 0, and p&#xa0;<&#xa0;0.001) and the Jaccard index (median: 0.44 vs. 0.00 and p&#xa0;<&#xa0;0.001) were significantly higher in the true recurrence group. Recurrence timing was inconsistently correlated with mutational concordance, although a 3-year cutoff yielded significant separation. CONCLUSION: Recurrence timing alone insufficiently reflects clonal relationships. Genomic profiling offers a reliable framework for distinguishing between recurrence types and guiding HCC management.

clonal relapse↗
PubMed2025

High-grade gliomas derived from an ovarian mature teratoma: clonal dynamics and genetic insights.

UNLABELLED: High-grade glioma (HGG) arising from a mature ovarian teratoma is extremely rare and its genetic alterations remain largely unknown. We report a case of WHO Grade 4 HGG (HGG-G4) developing 3 years after cystectomy for ovarian mature teratoma, where a WHO Grade 3 HGG (HGG-G3) was identified upon pathological reevaluation. Whole-exome sequencing confirmed the clonal relationship between HGG-G3 and HGG-G4, revealing genome-wide copy-neutral loss of heterozygosity, copy-number alterations, and whole-genome doubling in both HGGs. Genomic and epigenetic analyses have suggested multistep tumorigenesis and clonal alteration during the clinical course, particularly in response to chemotherapy, in HGGs arising from ovarian teratomas. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s13691-025-00790-x.

High-grade glioma↗
PubMed2007

Immortalized ovarian surface epithelial cells acquire tumorigenicity by Acrogranin gene overexpression.

Malignant transformation is caused by multi-step genetic mutations, and growth factors are believed to play important roles in developing and maintaining malignant phenotype. However, there is no direct evidence that a specific growth factor contributes to malignant transformation of phenotypically normal cells. In order to assess the function of Acrogranin (also known as granulin epithelial precursor; GEP) in ovarian carcinogenesis, ovarian surface epithelial (OSE) cells, which are supposed to be the origin of primary ovarian epithelial cancer, were transfected with combined genes of hTERT, SV40 LT, and Acrogranin. Introduction of hTERT and SV40 LT was sufficient for immortalizing OSE cells but not enough for tumor formation in nude mice. In contrast, transfection and overexpression of Acrogranin in immortalized OSE cells showed augmented clonogenicity in soft agar and obvious tumorigenicity in nude mice. This is the first study showing evidence that a specific growth factor plays a direct role in malignant transformation in ovarian cancer development.

Animals↗
PubMed2006

Ultrasound evaluation and clinical correlation of subscapularis repair after total shoulder arthroplasty.

The purpose of this study was to document the subscapularis healing rate by use of postoperative ultrasound and correlate healing to physical examination findings. We included 23 patients (30 shoulders), who underwent total shoulder arthroplasty in the study. The evaluation included a standard history and physical examination, ultrasound evaluation, and outcome questionnaires. The postoperative examination included careful documentation of an abdominal-compression test to evaluate subscapularis function. All patients had an improvement in functional outcome scores and shoulder range of motion. Of 30 shoulders, 26 (87%) had an intact subscapularis as determined by ultrasound. By use of ultrasound as the gold standard, the abdominal-compression test had 7 false-positive results, 3 false-negative results, 19 true-negative results, and 1 true-positive result. The sensitivity of the abdominal-compression test was 25%, and the specificity was 73%. The negative predictive value was 86%, and the positive predictive value was 13%. The abdominal-compression test demonstrated a low sensitivity, specificity, and positive predictive value in this study for the assessment of subscapularis function after total shoulder arthroplasty. If a subscapularis tear is suspected in a patient after total shoulder arthroplasty, the abdominal-compression test is unreliable in predicting a subscapularis defect.

Activities of Daily Living↗
PubMed2006

The demographic and morphological features of rotator cuff disease. A comparison of asymptomatic and symptomatic shoulders.

BACKGROUND: Very little comparative information is available regarding the demographic and morphological characteristics of asymptomatic and symptomatic rotator cuff tears. This information is important to provide insight into the natural history of rotator cuff disease and to identify which factors may be important in the development of pain. The purpose of the present study was to compare the morphological characteristics and prevalences of asymptomatic and symptomatic rotator cuff disease in patients who presented with unilateral shoulder pain. METHODS: Five hundred and eighty-eight consecutive patients in whom a standardized ultrasonographic study had been performed by an experienced radiologist for the assessment of unilateral shoulder pain were evaluated with regard to the presence and size of rotator cuff tears in each shoulder. The demographic factors that were analyzed included age, gender, side, and cuff thickness. All of these factors were evaluated with regard to their correlation with the presence of pain. RESULTS: Of the 588 consecutive patients who met the inclusion criteria, 212 had an intact rotator cuff bilaterally, 199 had a unilateral rotator cuff tear (either partial or full thickness), and 177 had a bilateral tear (either partial or full thickness). The presence of rotator cuff disease was highly correlated with age. The average age was 48.7 years for patients with no rotator cuff tear, 58.7 years for those with a unilateral tear, and 67.8 years for those with a bilateral tear. Logistic regression analysis indicated a 50% likelihood of a bilateral tear after the age of sixty-six years (p < 0.01). In patients with a bilateral rotator cuff tear in whom one tear was symptomatic and the other tear was asymptomatic, the symptomatic tear was significantly larger (p < 0.01). The average size of a symptomatic tear was 30% greater than that of an asymptomatic tear. Overall, patients who presented with a full-thickness symptomatic tear had a 35.5% prevalence of a full-thickness tear on the contralateral side. CONCLUSIONS: There is a high correlation between the onset of rotator cuff tears (either partial or full thickness) and increasing age. Bilateral rotator cuff disease, either symptomatic or asymptomatic, is common in patients who present with unilateral symptomatic disease. As the size of a tear appears to be an important factor in the development of symptoms, we recommend surveillance at yearly intervals for patients with known rotator cuff tears that are treated nonoperatively.

Female↗
PubMed2006

Proteomic analysis of a highly metastatic gastric cancer cell line using two-dimensional differential gel electrophoresis.

Stomach cancer is still a major cause of death in Asian people despite a complete cure after the resection of early cancers, mainly because peritoneal dissemination is difficult to treat. In the present study, we used two-dimensional differential gel electrophoresis (2-D DIGE) to identify specific proteins differentially expressed between a highly metastatic stomach cancer cell line MKN-45-P and its parental cell line MKN-45. We detected 27 protein spots in at least 2 of 3 experiments which showed statistically significant differences in abundance. All 27 protein spots were identified using matrix-assisted laser desorption/ionization-time of flight (MALDI-TOF) mass spectrometry (MS) and database-searching software. A proteomic analysis revealed 13 different proteins with some isoforms sharing different biochemical characteristics, and that 8 proteins were up-regulated, and 5 were down-regulated. The 13 proteins were mainly involved in protein synthesis (transfer RNA synthetase), metabolism (flavoprotein subunit, pyruvate kinase, adenylate kinase), receptor and signal transduction (annexins I and A2), the cytoskeleton (keratin 5, cytokeratin 8) and cell cycling (ts11). These results suggested that a proteomic approach including 2-D DIGE would be an efficient way to identify the proteins responsible for specific biological functions. Moreover, these observations might be novel findings leading to the prediction of postoperative peritoneal recurrence.

Cell Line, Tumor↗
PubMed2005

Clinical response in Japanese metastatic melanoma patients treated with peptide cocktail-pulsed dendritic cells.

BACKGROUND: Metastatic, chemotherapy-resistant melanoma is an intractable cancer with a very poor prognosis. As to immunotherapy targeting metastatic melanoma, HLA-A2+ patients were mainly enrolled in the study in Western countries. However, HLA-A24+ melanoma patients-oriented immunotherapy has not been fully investigated. In the present study, we investigated the effect of dendritic cell (DC)-based immunotherapy on metastatic melanoma patients with HLA-A2 or A24 genotype. METHODS: Nine cases of metastatic melanoma were enrolled into a phase I study of monocyte-derived dendritic cell (DC)-based immunotherapy. HLA-genotype analysis revealed 4 cases of HLA-A*0201, 1 of A*0206 and 4 of A*2402. Enriched monocytes were obtained using OptiPreptrade mark from leukapheresis products, and then incubated with GM-CSF and IL-4 in a closed serum-free system. After pulsing with a cocktail of 5 melanoma-associated synthetic peptides (gp100, tyrosinase, MAGE-2, MAGE-3 and MART-1 or MAGE-1) restricted to HLA-A2 or A24 and KLH, cells were cryopreserved until used. Finally, thawed DCs were washed and injected subcutaneously (s.c.) into the inguinal region in a dose-escalation manner. RESULTS: The mean percentage of DCs rated as lin-HLA-DR+ in melanoma patients was 46.4 +/- 15.6 %. Most of DCs expressed high level of co-stimulatory molecules and type1 phenotype (CD11c+HLA-DR+), while a moderate number of mature DCs with CD83 and CCR7 positive were contained in DC products. DC injections were well tolerated except for transient liver dysfunction (elevation of transaminases, Grade I-II). All 6 evaluable cases except for early PD showed positive immunological responses to more than 2 melanoma peptides in an ELISPOT assay. Two representative responders demonstrated strong HLA-class I protein expression in the tumor and very high scores of ELISPOT that might correlate to the regression of metastatic tumors. Clinical response through DC injections was as follows : 1CR, 1 PR, 1SD and 6 PD. All 59 DC injections in the phase I study were tolerable in terms of safety, however, the maximal tolerable dose of DCs was not determined. CONCLUSIONS: These results suggested that peptide cocktail-treated DC-based immunotherapy had the potential for utilizing as one of therapeutic tools against metastatic melanoma in Japan.

Journal Article↗
PubMed2005

Elbow arthroplasty using a convertible implant.

Total elbow arthroplasty remains the most definitive functional procedure for patients with end-stage painful arthritis of the elbow. Complication rates have historically been quite high, and early revision was not uncommon. A greater understanding of elbow anatomy and kinematics has led to advances in prosthetic design and surgical technique. The success of modern elbow arthroplasty for low-demand patients with rheumatoid arthritis has approached that of hip and knee arthroplasty. Mechanical failures have been noted to increase as a complication of both longevity and the use of elbow arthroplasty in a younger, higher-demand patient population. As the indications for total elbow arthroplasty widen to include more complex situations, it becomes more important to precisely recreate the flexion-extension axis of the elbow to optimally balance muscle forces and ligaments in an effort to improve implant durability. Advances in implant modularity and instrumentation can make determination and recreation of the flexion-extension axis more reliable and reproducible. An anatomic convertible implant allows the surgeon great versatility in choosing to perform hemiarthroplasty or unlinked or linked total elbow arthroplasty with assurance that later revision can be performed without the compulsory removal of well-fixed components. Conversion from an unlinked to a linked constraint, and visa versa, can be performed at any time. If late conversion is required, it can be performed in a minimally invasive fashion.

Arthritis↗
PubMed2005

Detection and measurement of rotator cuff tears with sonography: analysis of diagnostic errors.

OBJECTIVE: The purpose of this study was to analyze the causes of errors in the detection and measurement of rotator cuff tears in our patient population. SUBJECTS AND METHODS: Seventy-one consecutive patients with shoulder pain who were prospectively studied with sonography had subsequent arthroscopy that showed a full-thickness or partial-thickness tear or intact cuff. For sonography and arthroscopy, the length or degree of retraction and width of a tear, when present, was recorded. When there were discrepant findings, representative images were jointly evaluated by the radiologist and orthopedic surgeon to determine the cause of the error. RESULTS: Fifteen detection errors were found, including five misses (three < 5-mm subscapularis and two small partial-thickness tears), four errors inherent with the test (distinguishing large bursal side or extensive partial-thickness from full-thickness tears and tendinopathy from partial-thickness tears), three errors of an unknown cause, two due to misinterpretation, and one error inherent with the patient. Seventeen measurement errors occurred with full-thickness tears, 15 of those in patients with large or massive tears. Bursal thickening (n = 4), non-visualization of the torn tendon end (n = 2), nonretracted tear (n = 2), and complex tear (n = 1) contributed to the errors. Eight measurement errors occurred with partial-thickness tears. Difficulty distinguishing tendinopathy from partial-thickness tears (n = 3) and complex tears (n = 3) accounted for six errors. CONCLUSION: Although infrequent, detection errors were due to limitations inherent with the test or misses. Limitations inherent with the patient and misinterpretation of the findings were rare. Most measurement errors occurred in patients with large or massive cuff tears.

Arthroscopy↗
PubMed2005

Decision making in contemporary shoulder arthroplasty.

Clinical experience with humeral implants has evolved over the past decade, along with a better understanding of shoulder anatomy and function. There is no question that surgeons are getting better at restoring normal anatomic relationships than in preceding decades. Whether or not this impacts implant longevity will only be known with time and further follow-up. Even over the short term, it is difficult to ascertain whether new prosthetic designs have improved patient function as well as has been implied by the related biomechanical studies. Most surgeons with experience using old and new systems realize a greater sense of predictability in achieving their surgical goals when using more modern implants. Concerns over the durability of prosthetic systems with multiple moving parts and hand-tightened locking mechanisms have almost been forgotten in shoulder arthroplasty, but time will also reveal their importance. New glenoid designs have been less exciting, the major problem being one of developing appropriate materials. Polyethylene does not behave like normal cartilage, and its wear is constant and unforgiving. Surgeons now better understand how to reconstruct the normal glenoid position and achieve more secure early fixation than in the past, but this does not promise long-term durability and freedom from complications.

Arthroplasty, Replacement↗
PubMed2004

Antitumor effect induced by dendritic cell (DC)-based immunotherapy against peritoneal dissemination of the hamster pancreatic cancer.

Establishing a method to control peritoneal dissemination is one of the most pressing issues in the postsurgical treatment of pancreatic cancer. In the present study, we investigated the effect of dendritic cell (DC)-based immunotherapy on peritoneal disseminations of hamster pancreatic cancer cells, PGHAM-1. After the orthotopically inoculation of 2 x 10(6) PGHAM-1 cells, DC pulsed with PGHAM-1-derived tumor lysates, DC alone or PBS as a vehicle was injected intraperitoneally (i.p.) three times at weekly intervals. The group treated with DC or DC+lysate was found to have smaller disseminated tumors than the vehicle-treated. In addition, mean survival time in the DC+lysate groups was significantly longer than the PBS group. These findings suggested that DC-based immunotherapy might be efficient for the treatment of peritoneal disseminations of the pancreatic cancer.

Animals↗
PubMed2004

Gene dose mapping delineated boundaries of a large germline deletion responsible for multiple endocrine neoplasia type 1.

A deleted genomic region including the MEN1 gene was determined in a family with multiple endocrine neoplasia type 1 caused by a large germline deletion. Gene dose mapping by the modified gene dose assay technique roughly located the deletion end points, which were then precisely determined by nucleotide sequencing. The deletion was approximately 68kbp flanked by a 3-base pair repeat and included the whole MEN1, MAP4K2 and KAPPA-200 genes. This is the first case of a large germline deletion responsible for multiple endocrine neoplasia type 1, in which the size and end points were determined precisely.

Base Sequence↗
PubMed2004

Total elbow anthroplasty and distal humerus elbow fractures.

Palvanen et al in 2003 collected data on osteoporotic fractures of the distal humerus fractures from the Finnish National Hospital Discharge Register. They defined an osteoporotic fracture of the distal humerus as a fracture occurring in persons 60 years of age or older following moderate or minimal trauma. The annual rate of incidence of these types of fractures has increased significantly, with 42 fractures reported in 1970 and 208 fractures in 2000(395% increase). The age-specific incidence rates showed a ninefold increase for women 80 years of age or older (8 in 1970 versus 75 in 2000). In the 60-69-year and 70-79-year age groups, the age adjusted increases were twofold. This presents great challenges for future orthopedists, reinforcing the ongoing need to critically analyze results of treatment for this difficult problem. Many patients over the age of 60 years can do well with traditional open reduction and internal fixation of distal humerus fractures. When patients have poor bone quality, however, preventing stable internal fixation or significant medical comorbidities, TEA should be considered. Encouraging results have been reported using TEA as a primary mode of treatment for carefully selected comminuted distal humerus fractures in elderly patients, particularly if the patient also has significant rheumatoid arthritic changes. A triceps-sparing approach is recommended so that patients may be mobilized early following surgery.

Aged↗
PubMed2004

Analysis of HLA-A24-restricted CMVpp65 peptide-specific CTL with HLA-A*2402-CMVpp65 tetramer.

Developing precise and efficient methods of monitoring immune responses against cytomegalovirus (CMV) infection in immunocompromised transplantation patients is important. With the aim of optimizing the monitoring strategy, an HLA-A24-CMVpp65 tetramer-based analysis of CMVpp65 peptide-specific CTL lines was performed. Previously, the HLA-A24-restricted CTL epitope of CMVpp65 matrix protein was identified (QYDPVAALF aa 341-349). In the present study, CMVpp65 (aa 341-349) peptide-specific CTL lines were obtained from PBLs of 12 HLA-A24+ healthy donors by two stimulations with peptide-pulsed dendritic cells (DC). Among 12 CTL lines, 9 showed HLA-A*2402-CMVpp65 tetramer staining, which was found to be strongly co-related to the amount of IFN-gamma produced by CMVpp65 peptide-restimulated CTL lines (r=0.943, P<0.001). These results suggested that HLA-A*2402-CMVpp65 tetramer staining was an efficient way to monitor immune responses against CMV infection in HLA-A24+ immunocompromised hosts.

Apoptosis↗
PubMed2004

Recent advances in MEN1 gene study for pituitary tumor pathogenesis.

Evidence of multiple endocrine neoplasia type 1 (MEN1) is found in approximately 2.7% of patients with pituitary adenomas. The multicentricity of pituitary adenomas has not yet been proved. Prolactinomas are most frequent in MEN1 pituitary tumors. Pituitary tumors with MEN1 are larger in size and more aggressive than without MEN1. Heterozygous germline mutations of MEN1 gene are responsible for MEN1 disorders. Various types of mutations likely causing loss of the gene function have been identified throughout the entire region in patients with MEN1 and related disorders. However, the function of menin, the product of MEN1 gene, remains to be established. Neither mutation hot spot nor phenotype-genotype correlation has been established in classical MEN1. A number of recent studies suggest that somatic mutations in the MEN1 gene do not play prominent role in the pathogenesis of sporadic forms of pituitary adenoma.

Germ-Line Mutation↗
PubMed2004

The outcome and repair integrity of completely arthroscopically repaired large and massive rotator cuff tears.

BACKGROUND: The impact of a recurrent defect on the outcome after rotator cuff repair has been controversial. The purpose of this study was to evaluate the functional and anatomic results after arthroscopic repair of large and massive rotator cuff tears with use of ultrasound as an imaging modality to determine the postoperative integrity of the repair. METHODS: Eighteen patients who had complete arthroscopic repair of a tear measuring >2 cm in the transverse dimension were evaluated at a minimum of twelve months after surgery and again at two years after surgery. The evaluation consisted of a standardized history and physical examination as well as calculation of the preoperative and postoperative shoulder scores according to the system of the American Shoulder and Elbow Surgeons. The strength of both shoulders was quantitated postoperatively with use of a portable dynamometer. Ultrasound studies were performed with use of an established and validated protocol at a minimum of twelve months after surgery. RESULTS: Recurrent tears were seen in seventeen of the eighteen patients. Despite the absence of healing at twelve months after surgery, thirteen patients had an American Shoulder and Elbow Surgeons score of >/=90 points. Sixteen patients had an improvement in the functional outcome score, which increased from an average of 48.3 to 84.6 points. Sixteen patients had a decrease in pain, and twelve had no pain. Although eight patients had preoperative forward elevation to <95 degrees, all eighteen regained motion above shoulder level and had an average of 152 degrees of elevation. At the second evaluation, a minimum of twenty-four months after surgery, the average score, according to the system of the American Shoulder and Elbow Surgeons, had decreased to 79.9 points; only nine patients had a score of >/=90 points, and six patients had a score of </=79 points. The average forward elevation decreased to 142 degrees. CONCLUSIONS: Arthroscopic repair of large and massive rotator cuff tears led to a high percentage of recurrent defects. The minimum twelve-month evaluation showed excellent pain relief and improvement in the ability to perform activities of daily living despite the high rate of recurrent defects; however, at a minimum follow-up of two years, the results deteriorated with only twelve patients who had an American Shoulder and Elbow Surgeons score of >/=80.

Aged↗
PubMed2004

Primary hyperparathyroidism associatiated with aldosterone-producing adrenocortical adenoma and breast cancer: relation to MEN1 gene.

A rare case of primary hyperparathyroidism associated with primary aldosteronism and breast cancer is reported. A 44-year-old woman was admitted to our hospital to undergo surgical removal of breast cancer. She had hypertension with low serum potassium, and slightly but significantly elevated serum calcium levels. Further studies demonstrated an enlarged left superior parathyroid gland and a left aldosterone-producing adrenocortical adenoma. Blood pressure was controlled with spironolactone and nifedipine, and left mastectomy was done for breast cancer. The pathological diagnosis was scirrhous breast carcinoma. Although the postoperative course was uneventful, her serum calcium gradually and progressively rose to higher levels. Left superior parathyroidectomy and left adrenalectomy were then performed simultaneously. The pathological diagnoses of the resected parathyroid gland and adrenal gland were parathyroid chief cell adenoma and adrenocortical adenoma with hyperplasia of zona glomerulosa, respectively. To clarify if the occurence of these tumors may be related to MEN1 gene mutations, we analyzed MEN1 gene in this patient, and found a loss of heterozygosity of the MEN1 locus in the parathyroid adenoma and breast cancer. Thus, we conclude that an alteration of the MEN1 gene and/or another tumor suppressor gene located at the MEN1 locus on chromosome 11q13 may be responsible for the development of parathyroid adenoma and breast cancer in our patient suggesting that the clinical spectrum of MEN1 might include breast cancer. In addition, serum calcium should be interpreted with caution in primary aldosteronism, because hypercalcemia may be masked in the presence of aldosterone excess.

Adenoma↗