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Intraoperative identification of small pulmonary nodules has been an important technical issue. We aimed to develop a new localization method which is much safer and simple procedure compared with conventional methods.This was a retrospective study including patients with resected peripheral pulmonary nodules between November 2017 and April 2021 at Teikyo University School of Medicine, and Saitama Cardiovascular and Respiratory Center. All surgical procedure was wedge resection, and the tumor size was equal to or less than 20 mm which were detected by cone-beam computed tomography (CBCT; Philips Allura Xper FD 20, Philips). Some metal clips were put on several places of visceral pleura, where the target lesion was sandwiched by marking clips (sandwich marking technique). CBCT detected both the target lesion and metal clips, and video-assisted thoracoscopic surgery (VATS) was performed. Radiological and pathological findings were analyzed, and the correlation coefficient of tumor size was examined among pre-, intra-, and post-operative tumor sizes.The average age of 90 patients was 65.2 years, and 47 were male (52.2%). All procedure was wedge resection including twelve bi-wedge resections, and one hundred nine peripheral pulmonary lesions were obtained by sandwich marking technique. The detection rate was 100%, and there was no marking-related complication.All small peripheral pulmonary lesions were successfully detected and resected by using CBCT with no marking-related complication. Sandwich marking technique was demonstrated to provide safe, reliable, and simple localization procedure for small peripheral pulmonary lesions.

The Kushum is a relatively new breed of horses in Kazakhstan that was established in the middle of the 20th century through a cross between mares of Kazakhstan local horses and stallions of Thoroughbred, Trotter, and Russian Don breeds to supply military horses. To reveal the genetic characteristics of this breed, we investigated haplotypes of mitochondrial DNA (mtDNA) and single-nucleotide polymorphisms of the Y chromosome, as well as genotypes of five functional genes associated with coat color, body composition, and locomotion traits. We detected 10 mtDNA haplotypes that fell into 8 of the 17 major haplogroups of horse mtDNA, indicating a unique haplotype composition with high genetic diversity. We also found two Y-chromosomal haplotypes in Kushum horses, which likely originated from Trotter and/or Don breeds. The findings regarding the mtDNA and Y-chromosomal haplotypes are concordant with the documented maternal and paternal origins of the Kushum horses. The allele frequencies of ASIP, MC1R, and MATP associated with coat color were consistent with the coat color variations of Kushum horses. The allele frequencies of MSTN associated with endurance performance and those of DMRT3 associated with gait suggested that the observed allele frequencies of these genes were the result of selective breeding for these traits. As a result of this study, we were able to obtain useful information for a better understanding of the origin and breeding history of the Kushum horse breed using molecular markers.

Background The Dako PD-L1 immunohistochemistry (IHC) 22C3 pharmDx and the Dako 28-8 IHC pharmDx assays were approved by the US Food and Drug Administration, as a companion diagnostic test for pembrolizumab (Keytruda, Merk, Kenilworth, NJ, USA) and a complementary diagnostic test for nivolumab (Opdivo, Bristol Meyer Squibb, New York, NY, USA) in non-small cell lung cancer (NSCLC), respectively. Increased PD-L1 expression levels can be associated with greater therapeutic efficacy of pembrolizumab relative to other anti-PD-1 agents. However, in treatment decision making, little is known about which tissue (primary or metastatic lesion) should be stained by 22C3 antibody. We investigated the relationship between PD-L1 expression in primary tumors and paired metastatic lymph nodes using the 22C3 assay, and evaluated the concordance between the 22C3 and 28-8 assays. Methods PD-L1 expression was evaluated in cells from primary tumors and paired metastatic lymph nodes using the 22C3 and 28-8 IHC assays. Total 35 patients with primary tumor and paired metastatic lymph node were enrolled into this study, and all samples were surgically resected, formalin-fixed, and paraffin-embedded NSCLC tissues. Tumor cells exhibiting complete or partial membrane staining, were considered as PD-L1 positive. On the basis of tumor proportion score (TPS), all samples were classified as no expression (TPS

The recent development of human genome studies has demonstrated the possibility of alteration of several genes as oncogenic driver mutations of lung squamous cell carcinoma (SQCC). FGFR1, PIK3CA and SOX2 genes have been recognized as candidate driver genes of SQCC. The aim of the present study was to evaluate FGFR1, PIK3CA and SOX2 protein expression in SQCC and determine whether the expression of these can be used as prognostic biomarkers. We evaluated the relationships between FGFR1, PIK3CA and SOX2 expression by immunohistochemical analysis and overall survival in lung SQCC patients with stage I-III that originated from China, United States and Japan. FGFR1-positive, PIK3CA-negative and SOX2-positive staining each showed trends toward better survival, although the differences were not statistically significant in a Chinese cohort of 57 patients. Patients with PIK3CA-negative and SOX2-positive staining (PIK3CA(-)/SOX2(+)) showed better prognosis compared with those with PIK3CA-positive or SOX2-negative staining in the Chinese cohort (p=0.04). The robustness of PIK3CA(-)/SOX2(+) classification as having prognostic significance was validated in an independent set of 66 Japanese cohort patients (p=0.007). Japanese SQCC patients with stage I were evaluated separately and PIK3CA(-)/SOX2(+) cases had significantly better survival than the group with PIK3CA-positive or SOX2-negative status (p=0.03). In univariate and multivariable Cox proportional hazards models of Asian stage I patients, the PIK3CA(-)/SOX2(+) classification was statistically significantly associated with survival and was an independent prognostic factor. Classification by PIK3CA and SOX2 protein expression is useful for predicting the prognosis of Asian patients with lung SQCC with stage I.

Klotho is known as an anti-aging gene. We previously reported that the expression of Klotho is a postoperative prognostic factor for patients with lung large cell neuroendocrine carcinoma and lung small cell carcinoma. Recently, Klotho was shown to suppress the epithelial-mesenchymal transition (EMT). In the present study, we examined the association between the expression of Klotho and the regulation of EMT in lung squamous cell carcinoma. We immunohistochemically examined the expression of Klotho in patients with lung squamous cell carcinoma who had undergone surgical resection or photodynamic therapy. The immunohistochemical analysis showed that Klotho expression was observed not only in normal bronchial epithelial cells, but also in centrally located early lung cancers, which were all carcinomas in situ and were treated using PDT. However, in lung cancer patients with invasive and or advanced squamous cell carcinoma who had undergone a complete surgical resection, Klotho expression was observed in only 4 patients (13%). To elucidate the associations between the expression of Klotho and the expressions of EMT-related proteins, such as E-cadherin, N-cadherin, vimentin, and Snail, we transiently transfected GFP-Klotho plasmid DNA into the human squamous lung cancer cell line SQ5 and examined the expressions of these proteins of GFP-positive cells after sorting using flow cytometry. In SQ5 cells overexpressing GFP-Klotho, the expression of N-cadherin, which is a mesenchymal marker, was completely inhibited, compared with that in SQ5 cells transfected with the GFP vector. The overexpression of Klotho did not affect the regulation of either other mesenchymal markers (such as vimentin and Snail) or the regulation of an epithelial marker (E-cadherin). We concluded that the expression of Klotho was related to the degree of cancer invasiveness and that Klotho inhibits the expression of N-cadherin and regulates the EMT in lung cancer.

Introduction: Clinicopathological characteristics and prognosis of non-small cell lung cancer (NSCLC) patients with a family history of lung cancer (FHLC) have not been well established. Methods: Clinical records of patients with NSCLC treated at our institute from 1982 to 2010 were reviewed with special reference to family history of lung cancer and clinicopathological factors including patient's outcome. Univariate analyses of the factors between the groups of FHLC and non-FHLC were performed using unpaired two-tailed t tests or the chi-square test. The Cox proportional hazards model was used to evaluate the hazard ratio of death. Results: Of the 1013 NSCLC patients, 124 (12.2%) had a FHLC of whom 119 (96%) were the first-degree relatives. The frequency of early stages of lung cancer was high in both groups of FHLC and non-FHLC patients. Patients with FHLC had a significantly higher frequency of early pathological stages and a prepomderance of adenocarcinoma, and a hazard ratio of death of 0.870 (95% confidence interval: 0.599-1.263, p value: 0.465) compared with the non-FHLC patients. Conclusions: NSCLC patients with FHLC could be characterized by early pathological stages and preponderance of adenocarcinoma, however they were not at a decreased hazard ratio of death. These findings emphasize the importance of early detection of lung cancer and employment of less invasive therapeutic interventions.

Introduction: Clinicopathological characteristics and prognosis of non-small cell lung cancer (NSCLC) patients with a family history of lung cancer (FHLC) have not been well established.Methods: Clinical records of patients with NSCLC treated at our institute from 1982 to 2010 were reviewed with special reference to family history of lung cancer and clinicopathological factors including patient's outcome. Univariate analyses of the factors between the groups of FHLC and non-FHLC were performed using unpaired two-tailed t tests or the chi-square test. The Cox proportional hazards model was used to evaluate the hazard ratio of death.Results: Of the 1013 NSCLC patients, 124 (12.2%) had a FHLC of whom 119 (96%) were the first-degree relatives. The frequency of early stages of lung cancer was high in both groups of FHLC and non-FHLC patients. Patients with FHLC had a significantly higher frequency of early pathological stages and a prepomderance of adenocarcinoma, and a hazard ratio of death of 0.870 (95% confidence interval: 0.599-1.263, p value: 0.465) compared with the non-FHLC patients.Conclusions: NSCLC patients with FHLC could be characterized by early pathological stages and preponderance of adenocarcinoma, however they were not at a decreased hazard ratio of death. These findings emphasize the importance of early detection of lung cancer and employment of less invasive therapeutic interventions.

SUMMARYThe objective of the present study was to determine the optimal culling strategy in relation to biological and economic efficiency (BE and EE, respectively) and annualized net revenue (AN) in the Japanese Black cow–calf production system with special reference to the beef quality of culled cows. The herd model focused on two ways of mating: one-mating trial system (ONE) and continuous-mating trial system (CON). ONE assumed that heifers that fail to conceive are culled and cows that fail to conceive are culled at weaning of their calves, while CON assumed that mating continues until all females theoretically conceive. Least square means of carcass data of Japanese Black cows collected from a cooperative farm in Japan were used to estimate the carcass price of a cow by parity and Beef Marbling Standard (BMS) number. The simulation, assuming the current production situation in Japan, indicated that sales of culled cows accounted for 0·10–0·20 of total sales and was an important element in total production. Comparisons between ONE and CON showed that production efficiency in the current situation is higher in CON. The BE, EE and AN were higher in CON than in ONE. The two economic indicators were less sensitive to changes in annual discount rate but highly sensitive to changes in female calf price and BMS number of cows, indicating the importance of considering fluctuations in calf price and potential quality of culled cows’ carcasses when estimating the economically optimal parity of culling. The three indicators derived different optimal solutions even in the same mating trial systems, stressing the importance of choice of production indicators when determining the culling strategy and evaluating animal production.

This study was conducted to evaluate the importance of maternal effect on body measurement traits at an early stage of growth, and to estimate the genetic relationships between direct and maternal effects and among body measurement traits at 0 month (0-mo) and 4 months (4-mo) of age in a population of Japanese Black calves. Body measurements and body weight of 889 Japanese Black calves were estimated with the use of an animal model by the Residual Maximum Likelihood procedure. Direct heritabilities were low to moderate, ranging between 0.17 ± 0.09 and 0.48 ± 0.13 at 0-mo, and slightly lower, ranging between 0.15 ± 0.07 and 0.33 ± 0.13 at 4-mo. Estimated maternal heritabilities were low to moderate, ranging between 0.08 ± 0.07 and 0.33 ± 0.07 at 0-mo and 0.13 ± 0.06 to 0.33 ± 0.06 at 4-mo. The direct genetic correlations between 0-mo and 4-mo were moderate to highly positive, ranging from 0.53 ± 0.23 to 0.96 ± 0.09. The estimated direct genetic correlation of chest width with other width traits was low and positive at both ages, whereas with hip width it was high and positive (0.80 ± 0.09) at 0-mo, suggesting that simultaneous improvement of body width of the front and back parts is possible. Maternal genetic effects were relatively independent of direct genetic effects for body measurement traits and can be considered in genetic evaluation.

肺切除術後の肺血栓塞栓症（Pulmonary thromboembolism；PTE）は呼吸器外科術後合併症において，致死的な経過をたどることの多い極めて重篤な合併症である．今回我々は，10年前に左肺扁平上皮癌に対し左上葉切除術，縦隔リンパ節郭清術の既往のある，69歳の男性に対し，残肺全摘術，リンパ節郭清術を施行した．術後第10病日に突然PTEを発症したが，全身管理の末救命し得たので，文献的考察を踏まえ報告する．

本研究の目的は，アンケート調査を行い，肉牛飼養者の属性や意識の差異が農家ごとの枝肉価格と枝肉形質の最良線形不偏推定値（BLUE）に与える影響を調べることであった．アンケート調査は，安愚楽牧場と契約している農家を対象に行い，分析には肥育農家91戸のデータを用いた．最良線形不偏推定値（BLUE）の推定には，安愚楽牧場で2004年1月から2005年3月までに出荷された20,346頭の枝肉成績を用いた．農家ごとの枝肉価格と枝肉形質に関するBLUE値を目的変数とし，農家の属性や意識を取り入れ最小2乗分散分析を行った．分析の結果，経済性と生きがいをともに重視している農家の方が良質の枝肉を生産していることが明らかとなった．さらに，枝肉単価と飼養規模の間には2次曲線の関係があり，規模が大きくなるにつれ，枝肉単価は逓減し，932頭を境に増加していくことが明らかとなった．

Double inferior vena cava is a congenital venous anomaly that is found at about 1% to 3% of routine autopsies and has been described in numerous reports over the years. According to Adachi (1940), it has an incidence of 1.4±0.34%. More recently, diagnostic imaging has revealed that double inferior vena cava tends to be found in patients with hydronephrosis and various other conditions. During routine anatomical practice at Nippon Medical School in 2000, a case of double inferior vena cava was observed in a Japanese woman who had died of subarachnoid hemorrhage at 66 years of age. Bilateral inferior venae cavae, left renal vein, and transiliac vein were found through dissection. These findings are supplemented by a discussion of the literature with respect to embryological studies, morphological classifications, and disease correlations.

Laryngeal Hemiplegia (LH) leads to a reduction in performance and because of it many promising racehorses have been forced to end their racing career. Therefore it is important for breeding good racehorses to estimate theheritability of LH. In this study, the computer program was developed based on the Bayesian analysis with Gibbs sampling for estimating the heritability of categorical traits assuming liability. A total of 706 records with LH-grade in Thoroughbreds aged 2 to 5 years were assigned for the genetic analysis. LH-grades consisted of five severity classes from 0 to 4. Racehorse breeders are often interested in whether the genetic effect controlling a complex disorder is present in the population. To answer this question, the binary trait analysis would be also useful. The heritability of LH-grade in the Thoroughbred horse was then also estimated as a binary or as a categorical trait. The mode values ofthe posterior distributions of heritability were 0.23 and 0.20 for the binary and the categorical trait, respectively. The fact that in the Thoroughbred population studied LH is at least partially controlled by genetic factors leads to the suggestion that when applying adequate breeding measures the prevalence of LH will be able to be reduced.

Remnants of cardiomyocytes showing coagulation necrosis in the scars cau sed by myocar‑ dial infarction were histopathologically studied. Among 305 autopsy cases of acute and or healed myocardial infarction 8 cases（7 men 1 woman ages 62～87 years mean age 72.1）had masses of cardiomyocytes with coagulation necrosis at the center of the infarction scars more than 3 weeks（21 to 79 days）after the attack of myocardial infarction. All these cases had transmural infarction and more than 80％ of the wall thickness of the left ventricle was in‑ volved in the infarction. No polymorphonuclear leukocytic infiltration or granulation tissue was found in the necrotic area but macrophages were observed in the peripheral area adjacent to the scar tissue. Immunohistochemical staining for myoglobin showed no reaction in remnant necrotic cells or pericellular interstitium which was similar to findings in the necrotic area more than 4 days after the infarction. These findings are important in the pathological diagno‑ sis to distinguish remnant necrosis from acute necrosis because 4 out of 8 present cases （50％）were misdiagnosed as acute myocardial infarction that superimposed on the previous old infarction.（J Nippon Med Sch 2003; 70: 509―514）

Japanese Black cattle are at risk for genetic homogeneity due to intensive use of a few sires. Therefore, assessment of the actual genetic diversity of this breed is important for future breeding plans. In the present study, we investigated the genetic diversity within and among eight subpopulations of Japanese Black cattle using 52 microsatellite markers. The parameters for genetic diversity of Japanese Black cattle were comparable to those of other cattle breeds, suggesting that the relatively high genetic diversity of the breed. However, upon comparison among the eight subpopulations, the Hyogo subpopulation showed markedly low genetic diversity. The results of the pairwise FST values, phylogenetic network and structure analysis indicated that the Hyogo population has remarkably high level of genetic differentiation from other populations, while Yamagata, Niigata, Hiroshima and Kagawa populations have low levels of genetic differentiation. Furthermore, multidimensional scaling plots indicated that individuals in some subpopulations were separated from individuals in the other subpopulations. We conclude that while the overall genetic diversity of Japanese Black cattle is still maintained at a relatively high level, that of a particular subpopulation is significantly reduced, and therefore the effective population size of the breed needs to be controlled by correct mating strategies.

Thymoma has malignant potential and is the most common anterior mediastinal tumor. Video-assisted thoracic surgery (VATS), which is less invasive surgical procedure, is a good option for resecting Masaoka stage I tumors. Whether VATS is appropriate, depends on the surgeon's judgment and accurate imaging diagnosis. We introduce a technique involving a combination of video-assisted thoracoscopic thymectomy (VAT-T) and lateral thoracotomy for stage II and some stage III thymomas that have locally invaded the lung and/or pericardium.

Purpose We investigated surgical results of staple line coverage with a polyglycolic acid sheet plus pleural abrasion by thoracoscopic surgery for treating primary spontaneous pneumothorax in young patients. Methods Forty-seven patients younger than 40 years underwent 48 thoracoscopic surgical procedures for spontaneous pneumothorax at the Division of Thoracic Surgery, Department of Surgery, Nippon Medical School, from May 2007 through August 2010. All patients underwent thoracoscopic bullectomy with stapling devices and pleural abrasion performed with a gauze sponge held by forceps until the pleura became petechial. Finally, the staple line was covered with a polyglycolic acid sheet (10 × 10 cm). No fibrin glue was used. We investigated both short-time results after surgery and the postoperative recurrence of pneumothorax. Results There was no operative mortality or morbidity, such as air leakage from staple lines or hemorrhage due to pleural abrasion. Pneumothorax recurred after surgery in 3 cases. In 2 cases, neither re-operation nor tube thoracostomy was necessary because intrapleural adhesions allowed only partial collapse of the lung. One patient underwent re-operation for an overlooked bulla facing the diaphragm in left lower lobe of the lung 2 days after the first operation. The rate of freedom from pneumothorax 4 years after surgery was 94%. Conclusions Staple line coverage with a polyglycolic acid sheet plus pleural abrasion by thoracoscopic surgery is a useful method for preventing morbidity and the postoperative recurrence of pneumothorax.

Marbling in beef, measured by Beef Marbling Standard (BMS) number, is an economically important trait for beef cattle breeding and markets in Japan. We previously detected three single nucleotide polymorphisms (SNPs) associated with BMS number of Japanese Black in Oita prefecture: c.*188GA in AKIRIN2, g.1471620GT in EDG1 and g.3109537CT in RPL27A. Here, we carried out single and multiple marker association analyses for the three SNPs in a different commercial Japanese Black population of 892 genotyped animals. The single marker analyses with the model including a single SNP showed significant associations of all SNPs with BMS number. The multiple marker analysis with the model including the main effects of the three SNPs and their interactions detected only significant main effects of g.1471620GT and g.3109537CT and a significant interaction between c.*188GA and g.1471620GT. These findings suggest the presence of inter-allelic interactions among genes affecting the development of beef marbling. For effective marker-assisted selection for BMS number, interactions among these markers need to be considered.

Estimates of genetic parameters were obtained for body measurement traits of 648 animals at 4 months of age, of 545 at 8 months and carcass traits of 14 972 animals with the use of an animal model by the restricted maximum likelihood procedure. The estimated heritabilities for carcass traits were high (0.41 to 0.54). At 4 months the estimated direct heritabilities for body measurement traits were moderate to high (0.28 to 0.64), except for chest width (0.19); at 8 months they were also moderate to high (0.23 to 0.49), except for chest depth and chest width (0.18 and 0.06, respectively). Maternal heritabilities for all body measurement traits were low at both ages. The results indicate that because of their moderate direct genetic correlations with body measurement traits, carcass weight, rib thickness and subcutaneous fat thickness can be improved; however, rib eye area and beef marbling standard show little such possibility considering their correlation with body measurement traits.

Objective This study aimed to investigate whether perioperative inhalations of long-acting beta-agonists (LABAs) or long-acting muscarinic antagonists (LAMAs) might decrease the incidence of postoperative complications in lung cancer patients with chronic obstructive pulmonary disease (COPD). Methods We retrospectively analyzed 108 patients with COPD who underwent pulmonary resections for primary lung cancer at our hospital between January 2013 and January 2016 to determine the association between the incidence of postoperative complications (e.g., prolonged air leakage and pneumonia) and the use of LABAs or LAMAs. Results Thirty patients with COPD experienced postoperative complications (27.8%): Fourteen patients had prolonged air leakages (more than 7 days), ten patients developed pneumonia. The frequency of these postoperative pulmonary complications was significantly higher among the patients with COPD (24/108 cases, 22.2%), compared with the frequency among non-COPD patients (15/224 cases, 6.7%). Inhaled bronchodilators, such as LAMA or LABA, were prescribed for 34 of the 108 patients with COPD; the remaining 74 patients were not treated with bronchodilators. Pulmonary complications were significant lower among the LAMA or LABA users (3/34 cases, 8.8%) than among the untreated COPD patients (21/74 cases, 28.4%). Conclusion For lung cancer patients with COPD, preoperative management using LABA or LAMA bronchodilators and smoking cessation can reduce the frequency of postoperative pulmonary complications after surgical lung resection. LAMA or LABA inhalation might be useful for not only perioperative care, but also for the long-term survival of COPD patients after surgery.