Genetic Analysis Reveals Dispersal Patterns of Japanese Serow in Two Different Habitats of a Mountainous Region.

Dispersal increases the costs of feeding and predation risk in the new environment and is reported to be biased toward habitats similar to the natal region in some mammals. The benefits and costs of dispersal often differ between sexes, and most mammals show male-biased dispersal in relation to a polygamous mating system. Japanese serow is generally a solitary and monogamous species. However, recent studies have shown that the sociality of serows on Mt. Asama differs between habitat types. In the mountain forests with low forage availability, solitary habits and social monogamy were observed, while, in alpine grasslands, female grouping and social polygyny were observed, which is probably due to abundant forage availability. We investigated the effects of habitat characteristics and sociality on the dispersal of serows using fecal and tissue samples from two different habitats on Mt. Asama. The Fst value between the two areas was significantly positive, and the mean relatedness within areas was significantly higher than that between areas, which suggests limited gene flow and natal habitat-biased dispersal. Bayesian clustering analysis showed unidirectional gene flow from forest to grassland, which was probably due to the high forage availability of the grassland. Analyses of the assignment index and mean relatedness did not show male-biased dispersal, even in the grassland, where serows were polygynous. Thus, polygyny in the grassland is not linked to male-biased dispersal. In summary, our study suggests that dispersal patterns in Japanese serows are affected by habitat rather than social differences.

Surgery for pulmonary lesions in patients with a history of urinary tract transitional cell carcinoma.

BACKGROUND: There has been little information on the actual diagnosis of pulmonary lesions in patients with a history of urinary tract transitional cell carcinoma (TCC) and short- and long- outcomes of pulmonary resection for these patients. METHODS: In the present study, the data of 37 consecutive patients with a history of TCC who underwent pulmonary resection for solitary pulmonary lesions were reviewed, and the clinical factors and short- and long-term outcomes were analyzed. RESULTS: The study population included 35 male patients, and 2 female patients. The mean age was 72.5 years. Twenty patients (80%) were smokers and showed a high incidence of chronic obstructive pulmonary disease. Pulmonary lesions and primary TCC were detected simultaneously in 5 patients and metachronously in 32 patients. The median interval between treatment for primary TCC and the detection of pulmonary lesion was 43 months. The mean tumor diameter was 23 mm. The types of resection included lobectomy (n = 19), segmentectomy (n = 8), and partial resection (n = 10). Twelve of 37 patients (32%) developed postoperative complications. The pathological diagnoses included primary lung cancer (n = 28), pulmonary metastasis from TCC (n = 7), and others (n = 2). The 5-year overall survival rate for all patients was 72%. The 5-year overall survival rate of patients with primary lung cancer was 74%, while that of patients with pulmonary metastasis from TCC was 57%. CONCLUSIONS: Surgery can be proactively considered for treating pulmonary lesions in patients with a previous history of TCC, as it provides favorable long-term outcomes.

Integrated cardiothoracic team approach for complex lung transplantation procedures in Japan-current status and future direction.

The first lung transplant procedure in the world was performed in 1983, while in Japan that was first accomplished in 1998. Over the following 25 years, lung transplantation has become a viable treatment option for Japanese patients with a variety of end-stage lung diseases. Seventy cadaveric-donor lung (41 single, 29 bilateral), 11 bilateral living-donor lobar lung, and three heart-lung transplants have been performed with use of an integrated cardiothoracic team approach at medical facilities associated with Osaka University. Extremely advanced clinical and surgical skill sets are required to complete a lung transplant procedure, including surgical knowledge and techniques, as well as management of cardiovascular surgery, especially in regard to mechanical circulatory support (MCS), vascular anastomosis in difficult cases, and concomitant cardiac surgery. We have found that a collaborative effort by general thoracic and cardiac surgeons is an important key for success with lung transplantation. Complex lung transplant surgery and management in Japan are performed by use of an integrated cardiothoracic team approach, which has led to a synergistic impact on successful lung transplantation cases by capitalizing greatly on the experiences, techniques, and expertise of cardiac and thoracic experts. The present review is focused on the role of cardiac surgeons from the viewpoint of our experience with these cases.

[A Case of Advanced Gastric Cancer with Preoperative Liver Metastasis and Postoperative Adrenal Metastasis, That Obtained Long-Term Recurrence-Free Survival after Resection and Chemotherapy].

The case was a 70-year-old man of highly advanced gastric cancer with 2 liver metastases(S3, S8)and pancreatic invasion. Three courses of S-1 plus L-OHP(SOX therapy)were performed, and total gastrectomy and combined resection of the spleen and body and tail of the pancreas and partial resection of the liver S3 and S8 were performed after reduction of primary tumor and liver metastasis. S-1 therapy was continued for 1 year as postoperative adjuvant chemotherapy. Left adrenal metastasis was detected by CT, 1 year and 6 months after the operation. PET-CT revealed no other areas suspected of recurrence, so left adrenalectomy was performed through the retroperitoneal space. Radical resection was not achieved because adhesions and scarring from the previous surgery were severe. Paclitaxel plus Ramucirumab was started and after 10 courses, the disappearance of the tumor shadow was observed on enhanced CT, and PET-CT. Three years and 3 months after the initial surgery and 1 year and 8 months after resection of adrenal metastasis, the patient is alive without recurrence.

Utility of the surgical Apgar score for predicting the short- and long-term outcomes in non-small-cell lung cancer patients who undergo surgery.

OBJECTIVES: The surgical Apgar score (SAS) is a simple score that predicts postoperative complications based on 3 intraoperative valuables. The present study evaluated the association between the SAS and postoperative outcomes in non-small-cell lung cancer patients who underwent surgery. METHODS: A total of 585 patients who underwent lung resection were enrolled in the present study. We calculated the SAS of each patient and investigated its influence on the short- and long-term outcomes. RESULTS: Postoperative complications of any grade were detected in 164 cases (28%). The morbidity rate increased with decreasing SAS. When all the patients were divided into 2 groups (SAS <7 vs ≥7), postoperative complications were observed more frequently in the SAS <7 group than in the SAS ≥7 group (41% vs 25%, P < 0.001). In the multivariate analysis, the SAS was an independent risk factor for postoperative complications (odds ratio: 1.64 [1.03-2.61], P = 0.036). In terms of long-term outcomes, the 5-year disease-free survival (54.1% vs 73.2%, P < 0.001) and overall survival (73.8% vs 83.0%, P = 0.031) were significantly worse in the SAS <7 group than in the SAS ≥7 group. In a multivariate analysis, however, the SAS was not found to be an independent prognostic factor for either disease-free survival (hazard ratio: 1.39 [0.97-2.00], P = 0.075) or overall survival (hazard ratio: 0.90 [0.57-1.42], P = 0.642). CONCLUSIONS: The SAS reflected preoperative and intraoperative characteristics and was able to stratify the morbidity rate, suggesting it to be a useful predictor of short-term outcomes in non-small-cell lung cancer patients who undergo surgery.

Usefulness of positron-emission tomography for predicting the World Health Organization grade of thymic epithelial tumors.

BACKGROUND: It is often difficult to distinguish between thymoma and thymic carcinoma by preoperative radiological tests. While there have been some reports that the maximum standardized uptake value (SUVmax ) in positron emission tomography-computed tomography (PET-CT) is useful to this end, no large-scale analysis has been performed. We therefore analyzed the usefulness of the SUVmax and tumor size (TS) for differentiating thymic epithelial tumors. METHODS: From 2011 to 2019, 129 patients with thymic epithelial tumor who underwent PET-CT before surgical treatment were enrolled. The relevance of the SUVmax to the World Health Organization (WHO) histological type was assessed. To reduce the impact of the TS, the ratio of the SUVmax to the TS was also investigated. RESULTS: A total of 99 thymoma cases and 30 thymic carcinoma cases were enrolled into the study. The SUVmax and SUVmax /TS of thymic carcinoma were significantly higher than those of thymoma (SUVmax : 7.7 ± 3.4 vs. 3.3 ± 1.3, p < 0.01; SUVmax /TS: 1.5 ± 0.7 vs. 0.6 ± 0.4, p < 0.01). Focusing on the patients with a moderate SUVmax of ≤5 (84 thymoma and 4 thymic carcinoma), the SUVmax /TS values of thymic carcinoma were still significantly higher than those of thymoma (1.6 ± 0.8 vs. 0.6 ± 0.4, p < 0.01). CONCLUSIONS: PET-CT might provide significant information for differentiating images of thymoma and thymic carcinoma. We experienced several cases of thymic carcinoma with a moderate SUVmax of ≤5, and SUVmax /TS was considered a useful parameter for differentiating such cases.

Prognostic Impact of Number of Organ Invasions in Patients with Surgically Resected Thymoma.

PURPOSE: This study aimed to explore the clinical implications and prognostic value of the number of organ/structure invasions (NOI) in patients with thymoma after curative surgical resection. METHODS: We retrospectively analyzed 306 consecutive Japanese patients with thymoma who underwent curative surgical resection. Tumor invasions of pericardium, mediastinal pleura, phrenic nerve, lung, and venous structures were examined histopathologically. Cases were classified into four subgroups according to NOI: group 0, no tumor invasion; group 1, tumor invasion into single organ/structure; group 2, tumor invasion of two organs/structures; group 3, invasion of three or more organs/structures. Associations with NOI and several clinical characteristics and their prognostic significance were analyzed. RESULTS: Pleural invasion was found in 100 cases (32.7%), lung invasion in 48 cases (15.7%), pericardial invasion in 46 cases (15%), phrenic nerve invasion in 29 (9.5%), and venous invasion in 22 cases (7.2%). NOI was classed as group 0 in 201 cases (65.0%), group 1 in 42 cases (13.7%), group 2 in 20 cases (6.5%), and group 3 in 43 cases (14.1%). Cases with higher NOI showed significantly worse relapse-free survival (RFS) and overall survival (OS). Cox's proportional hazard model analysis also identified NOI as a prognostic factor affecting RFS and OS. CONCLUSIONS: Cases with higher NOI of thymoma after radical surgical resection showed significantly worse recurrence rates and survival.

Seasonal and geographical differences in the ruminal microbial and chloroplast composition of sika deer (Cervus nippon) in Japan.

To understand the nutritional status of culled wild sika deer (Cervus nippon), we compared the ruminal microbes of deer living in habitats differing in food composition (Nagano winter, Nagano spring, and Hokkaido winter) using next-generation sequencing. Twenty-nine sika deer were sampled. Alpha and beta diversity metrics determined via 16S and 18S rRNA amplicon-seq analysis showed compositional differences. Prevotella, Entodinium, and Piromyces were the dominant genera of bacteria, fungi and protozoa, respectively. Moreover, 66 bacterial taxa, 44 eukaryotic taxa, and 46 chloroplastic taxa were shown to differ significantly among the groups by the linear discriminant analysis effect size (LEfSe) technique. Total RNA-seq analysis yielded 397 significantly differentially expressed transcripts (q < 0.05), of which 48 (q < 0.01) were correlated with the bacterial amplicon-seq results (Pearson correlation coefficient > 0.7). The ruminal microbial composition corresponded with the presence of different plants because the amplicon-seq results indicated that chloroplast from broadleaf trees and Stramenopiles-Alveolates-Rhizaria (SAR) were enriched in Nagano, whereas chloroplast from graminoids, Firmicutes and the dominant phylum of fungi were enriched in Hokkaido. These results could be related to the severe snow conditions in Hokkaido in winter and the richness of plants with leaves and acorns in Nagano in winter and spring. The findings are useful for understanding the nutritional status of wild sika deer.

[Surveillance Bronchoscopy after Lung Transplantation].

Acute cellular rejection( ACR) is one of the major complications of the acute phase after lung transplantation. In addition, ACR is considered to be a major cause of chronic lung allograft dysfunction (CLAD). Therefore, the diagnosis and treatment for ACR are major issues at transplantation facilities. Surveillance bronchoscopy( SB) is performed at many institutions as the golden standard for ACR diagnosis, and our hospital also implements long-term post-transplant monitoring of ACR as a preventive measure for CLAD. However, the suitability of SB may be questioned due to the risk of complications such as bleeding and pneumothorax. Here, we would like to report the results of SB in our department and discuss future diagnosis and treatment policy for ACR.

Prognostic impact of tumor volume in patients with complete resection of thymoma.

BACKGROUND: The impact of tumor volume on prognosis is unclear. We therefore investigated the correlation between tumor volume and prognosis in patients with complete resection of thymoma. METHODS: A total of 177 patients who underwent curative surgical resection for thymoma were retrospectively collected and reviewed. We performed a volumetric analysis of each case using the modified version of "Watchin GGO" and evaluated the relationship between tumor volume and recurrence. RESULTS: The median tumor size was 5.0 (range 0.5-15) cm, and the median tumor volume was 35.1 (range 0.265-881.0) cm3 . The Pearson product-moment correlation coefficient was 0.658, suggesting a moderately strong connection between tumor volume and tumor size. To determine the impact of tumor volume on tumor recurrence, receiver operating characteristic curves of the recurrence and tumor volume were calculated. The area under the curve was 0.65 (95% confidence interval [CI]: 0.51-0.80), and the optimal cutoff level of the tumor volume for recurrence was 82.6 cm3 , with a sensitivity and specificity of 0.64 (11/17) and 0.74 (119/160), respectively. Patients with tumors ≥82.6 cm3 had a significantly worse recurrence-free survival than those with smaller tumors (p = 0.0122, hazard ratio: 2.99), with 5-year recurrence rates of 74.9% (95% CI: 58.6%-86.3%) versus 88.9% (95% CI: 79.0%-94.4%). CONCLUSION: The volume of completely resectable thymoma may be a useful prognostic indicator.

Helminthes detected from wild sika deer (Cervus nippon centralis) in Kanto-Chubu region, Japan.

The helminth fauna of 105 sika deer (Cervus nippon centralis) captured in Yamanashi, Kanagawa and Nagano Prefectures, Japan was investigated during 2014-2019. As a result, 12 helminthes, i.e. 3 digeneans (Ogmocotyle sikae, Dicrocoelium chinensis and D. dendriticum), 8 nematodes (Gongylonema pulchrum, Dictyocaulus sp., Pygarginema sp., Spiculopteragia houdemeri, Chabaudstrongylus ninhae, Trichuris discolor, Oesophagostomum sikae and Oes. asperum), and 1 cestode (Moniezia sp.) were detected. To our knowledge, this is the first report of Pygarginema sp., Cha. ninhae, and Oes. asperum from sika deer in Japan. Some helminthes detected in the present study can infect livestock. Considering the possibility of the spread of the helminthes to livestock through deer excrement, it is important to promote understanding the parasite fauna in wild deer.

Occurrence patterns of crop-foraging sika deer distribution in an agriculture-forest landscape revealed by nitrogen stable isotopes.

Conflicts arising from the consumption of anthropogenic foods by wildlife are increasing worldwide. Conventional tools for evaluating the spatial distribution pattern of large terrestrial mammals that consume anthropogenic foods have various limitations, despite their importance in management to mitigate conflicts. In this study, we examined the spatial distribution pattern of crop-foraging sika deer by performing nitrogen stable isotope analyses of bone collagen. We evaluated whether crop-foraging deer lived closer to agricultural crop fields during the winter and spring, when crop production decreases. We found that female deer in proximity to agricultural crop fields during the winter and spring were more likely to be crop-foraging individuals. Furthermore, the likelihood of crop consumption by females decreased by half as the distance to agricultural crop fields increased to 5-10 km. We did not detect a significant trend in the spatial distribution of crop-foraging male deer. The findings of spatial distribution patterns of crop-foraging female deer will be useful for the establishment of management areas, such as zonation, for efficient removal of them.

Thymic Lymphoepithelial Carcinoma Associated with Epstein-Barr Virus: Experiences and Literature Review.

Thymic lymphoepithelial carcinoma (TLEC) is a primary thymic carcinoma that accounts for about 14% of all thymic epithelial tumors and is classified into 14 types. The histological morphology is similar to lymphoepithelioma, a type of undifferentiated nasopharyngeal carcinoma. It has been reported that squamous carcinoma accounts for approximately 80% of thymic carcinoma, followed by TLEC, which accounts for 6%. TLEC has been reported to be associated with Epstein-Barr virus (EBV), with EBV infection in TLEC tumor cells first noted by Lyvraz et al. in 1985. Tumors shown to be EBV-positive are classified as TLEC if lymphoplasmacytic infiltration is lacking. However, only about 50% of the cases are positive for EBV, which is lower compared to nasopharyngeal lymphoepithelioma. Instances of EBV infection in other types of thymic epithelial tumor have been reported at lower rates, which suggests that EBV infection may have an important influence on the carcinogenesis of TLEC, though the etiology is unknown. TLEC is a highly malignant tumor with poor prognosis, as affected patients have a median survival time of 22 months, according to 58 cases from the literature, while the 5-year survival rate is 34.4%. Presently, prognosis is not considered to be affected by the presence or absence of EBV positivity.

Periostin secreted by activated fibroblasts in idiopathic pulmonary fibrosis promotes tumorigenesis of non-small cell lung cancer.

Non-small cell lung cancer (NSCLC) patients with idiopathic pulmonary fibrosis (IPF) show poor prognosis. Periostin is an extracellular matrix protein highly expressed in the lung tissues of IPF. This study aimed to investigate the possibility that periostin secreted by fibroblasts derived from IPF lung might affect proliferation of NSCLC cells. Periostin was more highly expressed and secreted by fibroblasts from diseased human lung with IPF (DIPF) than by normal human lung fibroblasts (NHLF). Cocultivation of NSCLC cells with conditioned media (CM) from DIPF increased proliferation of NSCLC cells through pErk signaling, with this proliferation attenuated by periostin-neutralizing antibodies. Knockdown of integrin ß3, a subunit of the periostin receptor, in NSCLC cells suppressed proliferation of NSCLC cells promoted by recombinant human periostin and CM of DIPF. On in vivo examination, DIPF promoted tumor progression more than NHLF, and knockdown of integrin ß3 in NSCLC cells suppressed tumor progression promoted by DIPF. Fibroblasts derived from surgical specimens from IPF patients also increased secretion of periostin compared to those from non-IPF patients. Periostin secreted from IPF-activated fibroblasts plays critical roles in the proliferation of NSCLC cells. The present study provides a solid basis for considering periostin-targeted therapy for NSCLC patients with IPF.

Current status of inhaled nitric oxide therapy for lung transplantation in Japan: a nationwide survey.

OBJECTIVES: Currently, inhaled nitric oxide (NO) therapy for lung transplantation is not covered by public health insurance in Japan. In this study, we evaluated the perioperative use and safety of inhaled NO therapy for lung transplantation. METHODS: Data regarding the duration of treatment and adverse events of inhaled NO therapy were collected for all lung transplantations performed from January 1, 2015, to December 31, 2019, at nine lung transplant facilities in Japan. RESULTS: During the study period, lung transplants were performed in 357 patients, among whom inhaled NO therapy was administered to 349 patients (98%). The median initial and median maximum inhaled NO doses were 10 and 20 ppm, respectively. Inhaled NO therapy was introduced during surgery and continued postoperatively in 313 patients (90%) for a median of 4 days. Significant improvements in oxygenation and decreases in pulmonary arterial pressure were observed in patients receiving inhaled NO therapy. Side effects of inhaled NO therapy, such as methemoglobinemia, were observed in 15 patients (4%), with a significant incidence in patients aged < 18 years. CONCLUSIONS: Inhaled NO therapy was performed in almost all patients who underwent lung transplantation in Japan and showed reasonable efficacy. Therefore, public health insurance coverage for inhaled NO therapy during lung transplantation is recommended.

Preoperative evaluation and indications for pulmonary metastasectomy.

Pulmonary metastasectomy (PM) is an established treatment that can provide improved long-term survival for patients with metastatic tumor(s) in the lung. In the current era, where treatment options other than PM such as stereotactic body radiation therapy (SBRT), immunotherapy, and molecular-targeted therapy are available, thoracic surgeons should review the approach to the preoperative evaluation and the indications. Preoperative evaluation consists of history and physical examinations, physiological tests, and radiological examinations. Radiological examinations serve to identify the differential diagnosis of the pulmonary nodules, evaluate their precise number, location, and features, and search for extra thoracic metastases. The indication of PM should be considered from both physiological and oncological points of view. The general criteria for PM are as follows; (I) the patient has a good general condition, (II) the primary malignancy is controlled, (III) there is no other extrapulmonary metastases, and (IV) the pulmonary lesion(s) are thought to be completely resectable. In addition to the general eligibility criteria of PM, prognostic factors of each tumor type should be considered when deciding the indication for PM. When patients have multiple poor prognostic factors and/or a short disease-free interval (DFI), thoracic surgeons should not hesitate to observe the patient for a certain period before deciding on the indication for PM. A multidisciplinary discussion is needed in order to decide the indication for PM.

Risk factors for non-cancer death after surgery in patients with stage I non-small-cell lung cancer.

OBJECTIVES: With improvements in the outcome of treatment for non-small-cell lung cancer (NSCLC), other diseases may account for a high death rate after surgery in patients with stage I NSCLC. In the present study, we analysed the associations between the clinical factors and non-cancer death after surgery in these patients. METHODS: The records of 514 patients with stage I NSCLC who underwent surgery were retrospectively reviewed; a proportional hazards model for the subdistribution of a competing risk was conducted to define the risk factors for non-cancer death. RESULTS: The mean patient age was 67 years. A total of 367 patients (71%) underwent bilobectomy or lobectomy while 147 (29%) underwent sublobar resection. The pathological stage was IA in 386 (75%) and IB in 128 (25%) patients. Three patients (0.6%) died within 90 days after surgery, and 108 (21%) experienced postoperative complications. Until the time of writing this report, 83 patients had died during the follow-up. The cause of death was primary lung cancer in 38 (46%) patients and other diseases in 45 (54%) patients, including non-cancer causes in 29 patients, such as pneumonia, cardiac death and cerebral stroke. According to a multivariable competing risk analysis for non-cancer death age (≥70 years), sex (male), body mass index (BMI <18.5), postoperative complications and % forced expiratory volume in 1 s (<80) were identified as risk factors for postoperative non-cancer death. CONCLUSIONS: Advanced age (≥70 years), male sex, low BMI (<18.5), postoperative complications and low preoperative % forced expiratory volume in 1 s (<80) were found to be the risk factors for postoperative non-cancer death after surgery in patients with stage I NSCLC.

Hepatocyte growth factor ameliorates methylglyoxal-induced peritoneal inflammation and fibrosis in mouse model.

BACKGROUND: Peritoneal dialysis (PD) is essential for patients with end-stage renal disease. Peritoneal fibrosis (PF) is a complex inflammatory, fibrogenic process. No effective treatments are available to prevent these processes. Hepatocyte growth factor (HGF) possesses anti-inflammatory and anti-fibrotic properties. The aim of this study was to analyze whether HGF suppresses MGO-induced peritoneal inflammation and fibrosis in a mouse model. METHODS: PF was induced by intraperitoneal (IP) injections of MGO for 14 days. C57/BL/6 mice were divided into three groups: Sham group (only vehicle); Sham + MGO group (PF induced by MGO); and HGF + MGO group (PF mice treated with recombinant human-HGF). PF was assessed from tissue samples by Masson's trichrome staining. Inflammation and fibrosis-associated factors were assessed by immunohistochemistry and quantitative real-time PCR. RESULTS: MGO-injected mice showed significant thickening of the submesothelial compact zone with PF. Treatment with HGF significantly reduced PM thickness and suppressed the expression of collagen I and III and α-SMA. Expression of profibrotic and proinflammatory cytokines (TGF-ß, TNF-α, IL-1ß) was reduced by HGF treatment. The number of macrophages, and M1 and M2 macrophage-related markers, such as CD86, CD206, and CD163, was reduced in HGF + MGO mice. CONCLUSION: HGF attenuates MGO-induced PF in mice. Furthermore, HGF treatment reduces myofibroblast and macrophage infiltration, and attenuates the upregulated expression of proinflammatory and profibrotic genes in peritoneal tissues. HGF might be an effective approach to prevent the development of PF in patients undergoing PD.