PubMed Health⌕ Search

Biomedical subjects

Kimihiro Shimizu

Publications and source records attributed to Kimihiro Shimizu.

13 recordsLinked to original sources
PubMed2025

Stratifying Lung Adenocarcinoma Risk with Multi-ancestry Polygenic Risk Scores in East Asian Never-Smokers.

BACKGROUND: Lung adenocarcinoma (LUAD) in never-smokers is a major public health burden, especially among East Asian women. Polygenic risk scores (PRSs) are promising for risk stratification but are primarily developed in European-ancestry populations. We aimed to develop and validate single- and multi-ancestry PRSs for East Asian never-smokers to improve LUAD risk prediction. METHODS: PRSs were developed using genome-wide association study summary statistics from East Asian (8,002 cases; 20,782 controls) and European (2,058 cases; 5,575 controls) populations. Single-ancestry models included PRS-25, PRS-CT, and LDpred2; multi-ancestry models included LDpred2+PRS-EUR128, PRS-CSx, and CT-SLEB. Performance was evaluated in independent East Asian data from the Female Lung Cancer Consortium (FLCCA) and externally validated in the Nanjing Lung Cancer Cohort (NJLCC). We assessed predictive accuracy via AUC, with 10-year and (age 30-80) absolute risks estimates. RESULTS: The best multi-ancestry PRS, using East Asian and European data via CT-SLEB (clumping and thresholding, super learning, empirical Bayes), outperformed the best East Asian-only PRS (LDpred2; AUC=0.629, 95% CI:0.618,0.641), achieving an AUC of 0.640 (95% CI:0.629,0.653) and odds ratio of 1.71 (95% CI:1.61,1.82) per SD increase. NJLCC Validation confirmed robust performance (AUC =0.649, 95% CI: 0.623, 0.676). The top 20% PRS group had a 3.92-fold higher LUAD risk than the bottom 20%. Further, the top 5% PRS group reached a 6.69% lifetime absolute risk. Notably, this group reached the average population 10-year LUAD risk at age 50 (0.42%) by age 41, nine years earlier. CONCLUSIONS: Multi-ancestry PRS approaches enhance LUAD risk stratification in East Asian never-smokers, with consistent external validation, suggesting future clinical utility.

East Asian never smokers↗
PubMed2006

Successful video-assisted mediastinoscopic drainage of descending necrotizing mediastinitis.

Descending necrotizing mediastinitis is an uncommon form of mediastinitis that can rapidly progress to septacemia. To date, the optimal surgical approach has remained controversial. We report a case of descending necrotizing mediastinitis that was treated successfully through a transcervical approach with video-assisted mediastinoscopy. In our case, because the abscess was separated into small compartments, especially in the paratracheal space, the abscess was drained using video-assisted mediastinoscopy. This less-invasive approach may be an option in the treatment of descending necrotizing mediastinitis, especially when the abscess in the paratracheal space is separated into small compartments.

Abscess↗
PubMed2005

Extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue (MALT lymphoma) in the thymus: report of four cases.

Mucosa-associated lymphoid tissue (MALT) lymphoma in the thymus is extremely rare, and little is known about its clinicopathological features. In this study, we examined four cases of MALT lymphoma in the thymus at our institute in terms of clinicopathological features. Most patients had autoimmune disease or hyperglobulinemia, and they also had cysts in the tumors. Both elevated serum levels of autoantibodies and the polyclonal increase in serum Ig remained almost unchanged after total thymectomy in all patients. We recommend that MALT lymphoma in the thymus should be considered in the differential diagnosis when a cystic thymic mass is found and if the patient is Asian and/or has autoimmune disease or hyperglobulinemia.

Adult↗
PubMed2005

Successful treatment of subarachnoid-pleural fistula using pericardial fat pad and fibrin glue after chest wall resection for lung cancer.

A 46-year-old male underwent a right adrenalectomy and a left upper lobectomy with an en-block resection of the involved chest wall. The proximal rib resections (third and fourth ribs) were performed at the costvertebral joints. Hemorrhage occurred from near the 3rd intervertebral foramen. The bleeding site was packed with oxycellulose to control the bleeding. Two hours after the operation, the patient complained of paraplegia due to spinal cord compression caused by swollen oxycellulose. An emergency operation was performed. The oxycellulose was carefully removed from the intervertebral foramen. Cerebrospinal fluid was exudated from the spinal canal, however, suggesting an iatrogenic subarachnoid-pleural fistula (ISPF). Autologous fat fragments individually combined with fibrin glue, was packed gently into the intervertebral foramen. The orifice of the foramen was then covered with a pericardial fat pad. The postoperative course was uneventful. This new technique is a direct and effective treatment for an ISPF.

Adipose Tissue↗
PubMed2005

Pulmonary pleomorphic liposarcoma.

Pulmonary liposarcoma is extremely rare with 6 cases previously reported in the English literature. The following is a report of a 36-year-old man with pulmonary liposarcoma. The patient had chest pain and a mass shadow in the right lower lung field was revealed on a chest X-ray film. A computed tomography and magnetic resonance imaging showed a heterogeneous tumor, compressing the right lower lobe of the lung. Because of the fatty tissue component in the tumor on the chest computed tomography, and the appearance as an extrapulmonary mass, preoperative diagnosis was posterior mediastinal liposarcoma. But thoracotomy revealed that the tumor originated from the lung. Right lower lobectomy and lymph node dissection was carried out with no additional therapy. The pathological diagnosis was pleomorphic liposarcoma originated from the lung. Two months after the operation, the patient died of respiratory failure due to local recurrence.

Adult↗
PubMed2005

Late-onset chylothorax after pulmonary resection and systematic mediastinal lymph node dissection for lung cancer.

Late-onset chylothorax occurred 49 days after right lower lobectomy for lung cancer in a 76-year-old man. Chylothorax was successfully managed by conservative treatment with chest tube drainage and an enteral low-fat diet. Chylothorax may occur in the late period after pulmonary resection and systematic mediastinal lymph node dissection for lung cancer, for which conservative management is the treatment of choice.

Aged↗
PubMed2005

Visceral pleural invasion is an invasive and aggressive indicator of non-small cell lung cancer.

OBJECTIVE: Although visceral pleural invasion by non-small cell lung cancer is considered a poor-prognostic factor, further information is lacking, especially in relation to other clinicopathologic prognostic factors. We assessed the relationship between visceral pleural invasion and other clinicopathologic characteristics and evaluated its significance as a prognostic factor. METHODS: We reviewed 1074 patients with surgically resected T1/2 non-small cell lung cancer for their clinicopathologic characteristics and prognoses. The patients were divided into 2 groups according to visceral pleural invasion status (visceral pleural invasion group and non-visceral pleural invasion group). Both groups were compared with regard to age, sex, histology, tumor size, tumor differentiation, lymph node involvement, lymphatic invasion, vascular invasion, scar grade, nuclear atypia, mitotic index, serum carcinoembryonic antigen level, and survival. Univariate and multivariate analyses were conducted. RESULTS: Visceral pleural invasion was identified in 288 (26.8%) of the resected specimens. Survival was 76.0% at 5 years and 53.2% at 10 years in the non-visceral pleural invasion group and was 49.8% at 5 years and 37.0% at 10 years in the visceral pleural invasion group. The difference between groups was highly significant ( P < .0001). Visceral pleural invasion was also significantly associated with a higher frequency of lymph node involvement. However, regardless of N status (N0 or N1/2), there was a significant difference in survival when the visceral pleura was invaded. Visceral pleural invasion was observed significantly more frequently in tumors with factors indicative of tumor aggressiveness/invasiveness: moderate/poor differentiation, lymphatic invasion, vascular invasion, high scar grade, high nuclear atypia grade, high mitotic index, and high serum carcinoembryonic antigen level. By multivariate analysis, visceral pleural invasion proved to be a significant independent predictor of poor prognosis in non-small-cell lung cancer patients with or without lymph node involvement. CONCLUSIONS: Visceral pleural invasion is a significant poor-prognostic factor, regardless of N status. Our analyses indicated that visceral pleural invasion is an independent indicator of non-small cell lung cancer invasiveness and aggressiveness.

Aged↗
PubMed2004

Visceral pleural invasion classification in non-small cell lung cancer: a proposal on the basis of outcome assessment.

OBJECTIVE: The definition of visceral pleural invasion in lung cancer TNM classification of the International Union Against Cancer lacks detail. The purpose of this study was to evaluate the significance of the extent of pleural involvement as a prognostic factor and to propose a refined TNM classification on the basis of visceral pleural invasion. METHODS: We reviewed 1653 consecutive patients with T1, T2, and T3 surgically resected non-small cell lung cancer for their clinicopathologic characteristics and prognoses. Visceral pleural invasion was classified by using the Japan Lung Cancer Society criteria: p0, tumor with no pleural involvement beyond its elastic layer; p1, tumor extension beyond the elastic layer but no exposure on the pleural surface; and p2, tumor exposure on the pleural surface. RESULTS: The 5-year survivals for patients with p1 or p2 tumors of 3 cm or less were identical and significantly worse than those for patients with p0 tumors of the same size. Patients with p1 or p2 tumors of greater than 3 cm and patients with T3 cancers had essentially identical survivals. CONCLUSIONS: Visceral pleural invasion should be defined as tumor extension beyond the elastic layer of the visceral pleura, regardless of its exposure on the pleural surface. A tumor of 3 cm or less with visceral pleural invasion should remain classified as a T2 tumor, as presently occurs in the International Union Against Cancer staging system, and tumors of greater than 3 cm with visceral pleural invasion should be upgraded to T3 status in the International Union Against Cancer TNM classification.

Adult↗
PubMed2003

Pathogenetic and biologic significance of TP14ARF alterations in nonsmall cell lung carcinoma.

The INK4a/ARF locus on human chromosome band 9p21 carries two tumor suppressor genes, TP14ARF and TP16INK4a, and both are frequently inactivated in nonsmall cell lung carcinoma (NSCLC. TP14ARF and TP16INK4a play important roles in the TP53 and RB tumor suppressor pathways, respectively. To elucidate the genetic and epigenetic status of the TP14ARF and TP16INK4a genes in NSCLC, we comprehensively analyzed mutations, homozygous deletions, methylations in the CpG regions, and expression of the TP14ARF and TP16INK4a genes in 31 NSCLC cell lines. TP16INK4a (84%) was inactivated more frequently than TP14ARF (55%). Moreover, p16INK4a was inactivated in all 17 cell lines with TP14ARF inactivation. Three cell lines with base substitutions in exon 2 resulted in missense mutations of TP16INK4a but silent mutations of TP14ARF. There was a case of mutation in exon 1alpha unique to TP16INK4a, but not a mutation in exon 1beta unique to TP14ARF. The TP16INK4a gene was methylated in 6 cell lines, but the TP14ARF gene was not methylated in any cell line. Unlike a mutually exclusive relationship for inactivation between TP16INK4a and RB, TP14ARF and TP53 did not show such a relationship (P = 0.61, Fisher exact test). Thus, the present results indicate the TP16INK4a gene to be the primary target of INK4a/ARF locus alterations. Transient TP14ARF expression induced G1 arrest in the cells with wild-type TP53, but not in the cells with mutated TP53. Thus, the pathogenetic and biologic significance of TP14ARF inactivation is different between NSCLC cells with wild-type TP53 and those with mutated TP53.

Blotting, Western↗
PubMed2002

Alterations in the INK4a/ARF locus and their effects on the growth of human osteosarcoma cell lines.

Two different proteins, p16(INK4a) and p14(ARF), encoded by the INK4a/ARF locus play important roles in the RB and p53 pathways, respectively. This study was performed to determine genetic and epigenetic alterations in the INK4a/ARF locus and their effects on the growth of osteosarcoma. Among six cell lines examined, both p16(INK4a) and p14(ARF) exons were homozygously deleted in two cell lines, MG63 and HOS, and both p16(INK4a) and p14(ARF) promoters were methylated in one cell line, U2OS. Wild-type mRNA and proteins for p16(INK4a) and p14(ARF) were expressed in three other cell lines, SaOS2, HuO9, and G292. Transfection studies were performed using two cell lines, U2OS and MG63. Both the RB and p53 genes were wild types in U2OS, whereas p53 but not RB was mutated in MG63. Both p16(INK4a) and p14(ARF) suppressed the growth of U2OS, whereas p16(INK4a) but not p14(ARF) suppressed the growth of MG63. p53 only did not suppress the growth of MG63 either; however, coexpression of p14(ARF) with p53 increased the fraction of the G0/G1 phase in MG63 cells. The data presented here demonstrate the importance of genetic and epigenetic alterations in the INK4a/ARF locus for the growth of osteosarcoma and thus will be useful to further understand the biologic behavior of osteosarcoma in association with the defects in the p53 and RB pathways.

Blotting, Western↗
PubMed2002

Successful management of solitary malar metastasis from lung cancer.

A right malar mass developed in a 68-year-old man who had undergone right upper and middle bilobectomy for lung cancer 2 years previously. The mass was diagnosed to be a malar metastasis from lung cancer and was surgically resected because no other metastases were found. The patient is well without signs of recurrence 5 years after resection of the malar mass. This is the first report of a malar metastasis from lung cancer and of successful resection for malar metastasis.

Aged↗
PubMed2002

Treatment strategy for chylothorax after pulmonary resection and lymph node dissection for lung cancer.

OBJECTIVE: We reviewed our experience with iatrogenic chylothorax after pulmonary resections for lung cancer to evaluate our treatment strategy and to identify factors that predict the need for reoperation. METHODS: From July 1992 through February 2000, a total of 1110 patients underwent pulmonary resection (at least lobectomy) and systematic mediastinal lymph node dissection for lung cancer at our division. Twenty-seven patients (2.4%) had postoperative chylothorax develop. We initially treated 26 of these patients conservatively with complete oral intake cessation and total parenteral nutrition, and these patients constituted the subjects in this study. RESULTS: There were 21 men and 5 women with a median age of 62 years (range 44 to 80 years). The initial procedures were pneumonectomy in 2 cases, bilobectomy in 1 case, and lobectomy in 23 cases. Twenty-one patients (81%) had the condition cured with conservative treatment. These patients resumed a normal diet at a median of 8 days after chylothorax diagnosis (range 4-35 days). The remaining 5 patients (19%) underwent reoperation at a median of 14 days after diagnosis (range 5-35 days). Chest tube drainage of less than 500 mL during the first 24 hours after complete oral intake cessation and total parenteral nutrition predicted a cure with conservative treatment. CONCLUSION: Although most cases of chylothorax after pulmonary resection with systematic mediastinal lymph node dissection can be cured with a conservative strategy, early surgical intervention may be indicated if chest tube drainage is more than 500 mL during the first 24 hours after complete oral intake cessation and total parenteral nutrition.

Adult↗