Haemophilia and cardiovascular disease in Japan: Low incidence rates from ADVANCE Japan baseline data.

INTRODUCTION: With the increasing life expectancy of people with haemophilia, the risk of cardiovascular disease (CVD) and thrombotic events has become a growing concern. Longitudinal studies on the incidence and risk factors of CVD in this population are limited, and optimal prevention and treatment strategies are yet to be established. AIM: This study aimed to present the baseline data of a prospective longitudinal study focusing on a subset of Japanese patients with haemophilia, specifically investigated the incidence, risk factors and treatment modalities for CVD and thrombotic diseases in people aged 40 years in Japan over 10 years through the ADVANCE Japan study. METHODS: The ADVANCE Japan study is a prospective multicentre cohort study involving 600 adult individuals with haemophilia A/B aged 40 years in Japan. The primary endpoint was the incidence of CVD, with secondary endpoints encompassing anticoagulant use, mortality rates, and comparison with the general population. RESULTS: Baseline data from the 600 participants revealed that thrombotic events occurred in 13 individuals (2.2%), mostly in those with haemophilia A. Atrial fibrillation was observed in 11 participants (1.8%). Hypertension and dyslipidaemia were identified as the prevalent risk factors. Various prophylactic treatments were employed, and no severe bleeding events were observed during the study period. CONCLUSION: This study provides vital baseline data for a 10-year prospective investigation of CVD and thrombotic disease risk in people with haemophilia. These findings will contribute to refining prevention and treatment approaches and improving patients' quality of life.

Relationship between CD4+ T-cell counts at baseline and initial periodontal treatment efficacy in patients undergoing treatment for HIV infection: A retrospective observational study.

AIM: To retrospectively investigate the relationship between the CD4+ T-cell counts at baseline and the efficacy of the initial periodontal treatment of patients undergoing treatment for human immunodeficiency virus (HIV) infection using the periodontal inflamed surface area (PISA). MATERIALS AND METHODS: Thirty-three patients with chronic periodontitis who had undergone periodontal examination at baseline and after the initial periodontal treatment were enrolled. PISA was calculated from the periodontal probing depth and bleeding on probing, and the ratio of PISA after treatment to that at baseline (PISA response ratio) was calculated. Groups with a response ratio of <1 and ≥1 were defined as the improvement and the non-improvement groups, respectively. RESULTS: PISA after the initial periodontal treatment significantly decreased compared with that at baseline (p < .05). A weak negative correlation was found between the PISA response ratio and CD4+ T-cell counts at baseline (p < .05). The CD4+ T-cell counts at baseline were significantly higher in the improvement group than in the non-improvement group (p < .05). Multivariate analysis revealed that the CD4+ T-cell counts at baseline was an independent factor that affects the PISA (p < .05). CONCLUSIONS: The higher the CD4+ T-cell counts at baseline in patients undergoing treatment for HIV infection, the more effective the initial periodontal treatment.

Ischaemic events are rare, and the prevalence of hypertension is not high in Japanese adults with haemophilia: First multicentre study in Asia.

INTRODUCTION: With the increasing life expectancy of patients with haemophilia (PWH), the number of PWH with age-related comorbidities, such as ischaemic events, is increasing. AIM: We conducted this multicentre observational study to identify the risk factors for major ischaemic events in PWH. METHODS: This study was the first multicentre observational study, conducted with the participation of five haemophilia treatment centres in Japan, conducted in ≥30-year-old adult PWH. The latest data recorded in the medical charts between 1 January and 31 December 2016 were reviewed. Healthcare data collected from the National Health and Nutrition Survey were used as the control data. RESULTS: Data of a total of 711 patients were collected. Only two PWH (0.3%) had a history of ischaemic events. Age-adjusted analysis indicated that the prevalence of hypertension defined as a blood pressure of 140/90 mm Hg or over was similar in the PWH to that in the males of the general population. However, when hypertension was defined more strictly (≥130/85 mm Hg), the prevalence was significantly lower in PWH than in the general male population. The hypertension in PWH was associated with the age, BMI, CKD, HIV infection and inhibitors. In particular, the odds ratio for the presence of inhibitors was high (odds ratio = 7.529). CONCLUSION: Whether the present results can be attributed to Japanese ethnicity or to the presence of haemophilia per se remains uncertain. We propose to initiate a prospective study for further investigation.

Balloon-Based Organ Retractor With Increased Safety and Reduced Invasiveness During Video-Assisted Thoracoscopic Surgery.

OBJECTIVES: In recent years, video-assisted thoracoscopic surgery (VATS) has increasingly become the preferred technique for thoracic surgery. However, the inherent characteristics of the lungs as large, soft, slippery, and delicate creates difficulties for pulmonary surgery. In this article, we outline the development and assessment of a balloon-based organ retractor for VATS via collaboration between medical and engineering personnel. METHODS: A dry lab trial and accompanying questionnaire assessment were performed by a group of thoracic surgeons. Objective pressure measurements were obtained, and animal experiment on pigs was performed. RESULTS: In the dry lab trial, use of the developed organ retractor required significantly less time and resulted in fewer difficulties than using a Cherry Dissector. The measured pressure per mm2 of the developed retractor was clearly lower than that for the Cherry Dissector. The questionnaire completed by the surgeons following the dry lab and animal experiments showed that most of the surgeons (7 surgeons out of 9) were satisfied with the quality of the balloon-based retractor based on a score of 3.13 ± 0.28 (mean ± standard deviation) out of 4.0. During the animal experiment, the balloon-based retractor provided stable and clear viewing with minimal need for adjustment. CONCLUSION: This balloon-based retractor could contribute to increased safety and less-invasive VATS.

Double stenting with silicone and metallic stents for malignant airway stenosis.

For severe malignant airway stenosis, there are several types of commercially available airway stents, and each has its own advantages and disadvantages. We herein describe the safety and efficacy of combination stenting with silicone and metallic stents for patients with extended malignant airway stenosis. Seven patients with malignant airway stenosis were treated via combination stenting with a silicone stent and a metallic stent for extended airway stenosis from the central to peripheral airways. Five patients were diagnosed with advanced esophageal cancer, two of whom had tracheoesophageal fistulas. One patient had adenoid cystic carcinoma, and another had mediastinal tumor. There were no specific complications related to the double stenting. Combination stenting with silicone and metallic stents proved to be a safe option for patients with severe, extended, and complicated malignant airway stenosis.

Surgery or stereotactic body radiotherapy for elderly stage I lung cancer? A propensity score matching analysis.

PURPOSE: The aim of this study was to compare the outcomes of surgery and stereotactic body radiotherapy (SBRT) for elderly clinical stage I non-small cell lung cancer (NSCLC) patients. METHODS: Patients ≥80 years of age with clinical stage I NSCLC between August 2008 and December 2014 were treated either surgery or SBRT. Propensity score matching was performed to reduce bias in various clinicopathological factors. RESULTS: Surgery was performed in 57 cases and SBRT in 41 cases. In the surgery group, the operations included 34 lobectomies and 23 sublobar resections. In the SBRT group, 27 cases were given 48 Gy in 4 fractions, and 14 were given 60 Gy in 10 fractions. Similar characteristics were identified in age (82 years), gender (male:female ratio 2:1), tumor size (2.2 cm), carcinoembryonic antigen (3.6 ng/ml), Charlson comorbidity index (1), Glasgow prognostic scale (0), and forced expiratory volume in 1 s (1.7 L) after matching. Before matching, the 5-year overall survival (OS) in surgery (68.3%) was significantly better than that in SBRT (47.4%, p = 0.02), and the 5-year disease-specific survival (DSS) (94.1%, 78.2%, p = 0.17) was not significantly different between the groups. The difference in the 5-year OS became non-significant between the matched pairs (57.0%, 49.1%, p = 0.56). CONCLUSIONS: The outcomes of surgery and SBRT for elderly patients with the early stage NSCLC were roughly the same.

The surgical outcomes of lung cancer combined with interstitial pneumonia: a single-institution report.

PURPOSE: Several studies have reported that an acute exacerbation (AE) of idiopathic interstitial pneumonia (IIP) can occur after lung resection in patients with non-small cell lung cancer (NSCLC); however, the perioperative management strategy is controversial. METHODS: The data of lung cancer patients at Nagasaki University Hospital from June 1994 to October 2013 were retrospectively reviewed. RESULTS: Among all 1701 NSCLC patients who underwent lung resection, 59 (3.5%) had IIP. Five patients (8.5%) had an AE of IIP following lung resection, three (60%) of whom died in hospital. Univariate and multivariate analyses were performed to identify possible risk factors for AE. The univariate analyses identified LDH and the volume of blood loss as risk factors. The multivariate analysis identified no factors. The treatment for an AE included steroid pulse therapy and neutrophil elastase inhibitor therapy. Direct hemoperfusion with polymyxin B immobilized the fiber column and immunosuppressant therapy was attempted in some of the patients who did not respond to these treatments. CONCLUSION: Patients with lung cancer and IIP have a higher risk of chest surgery and a poor prognosis. Very careful surgery and perioperative management are needed, because AEs are often difficult to AE predict.

Ratio of C-reactive protein to albumin is a prognostic factor for operable non-small-cell lung cancer in elderly patients.

PURPOSE: The aim of this retrospective study was to evaluate inflammation-based scoring as a prognostic factor for operable non-small-cell lung cancer (NSCLC) in elderly patients. METHODS: We collected preoperative data from 108 patients aged above 80 years with NSCLC. Inflammation-based scoring systems, including the C-reactive protein to albumin ratio (CAR) and the Glasgow prognostic score (GPS), as well as other clinicopathological factors, were evaluated as potential prognostic factors. RESULTS: The median patient age was 82 (range 80-93) years and the 5-year overall and disease-specific survival rates were 49.7 and 73.9%, respectively. The cut-off value for CAR was calculated using a receiver operator characteristics analysis and patients were dichotomized accordingly. Patients with a low CAR had significantly higher overall survival than those with a high CAR (<0.028; 65.2% vs. ≥0.028; 31.0%, respectively; p < 0.01). In univariate analysis, female gender, a low Charlson comorbidity index of 0 or 1 and a low CAR were significantly identified in overall survival. On multivariate analysis, a low CAR (p = 0.03, hazard ratio: 2.13, 95% confidence interval 1.074-4.295) was identified as a significant prognostic factor. CONCLUSIONS: The preoperative CAR is a useful predictor of overall survival and could be a simple prognostic tool to help identify resectable NSCLC in elderly patients.

[Granuloma by Foreign Body Reaction to the Stapler Used for Partial Resection of the Lung].

A 66-year-old woman underwent right lower lobectomy and partial resection of the middle lobe for Stage I A double lung cancer. Five years after the operation, a routine computed tomography (CT) scan showed a mass on the staple line at the middle lobe. The mass was enlarged on CT scan after 6 months. A definitive diagnosis could not be made by bronchoscopic examination and fluoro-2-deoxy-glucose(FDG)/positron emission tomography( PET)-CT showed FDG uptake in the mass( early phase:SUVmax=3.24, late phase:SUVmax=4.31). Local recurrence of lung cancer was not completely denied, and right middle lobectomy was performed. Histopathologically, the resected specimen revealed granuloma with foreign body reaction. We should keep in mind the possibility of granuloma as differential diagnosis of lung cancer when using stapler.

Epidermal growth factor signals regulate dihydropyrimidine dehydrogenase expression in EGFR-mutated non-small-cell lung cancer.

BACKGROUND: It has been shown that epidermal growth factor receptor (EGFR) mutation status is associated with 5-fluorouracil (5-FU) sensitivity in non-small-cell lung cancer (NSCLC). However, the relationship between EGFR mutation status and dihydropyrimidine dehydrogenase (DPD), a 5-FU degrading enzyme, is unknown. METHODS: We elucidated the crosstalk among the EGFR signal cascade, the DPD gene (DPYD), and DPD protein expression via the transcription factor Sp1 and the effect of EGFR mutation status on the crosstalk. RESULTS: In the PC9 (exon19 E746-A750) study, EGF treatment induced up-regulation of both Sp1 and DPD; gefitinib, an EGFR-tyrosine kinase inhibitor (EGFR-TKI), and mithramycin A, a specific Sp-1 inhibitor, suppressed them. Among EGFR-mutated (PC9, HCC827; exon19 E746-A750 and H1975; exon21 L858R, T790M, gefitinib resistant) and -non-mutated (H1437, H1299) cell lines, EGF administration increased DPYD mRNA expression only in mutated cells (p < 0.05). Accordingly, gefitinib inhibited DPD protein expression only in PC9 and HCC827 cells, and mithramycin A inhibited it in EGFR-mutated cell lines, but not in wild-type. FU treatment decreased the level of cell viability more in gefitinib-treated EGFR-TKI sensitive cell lines. Further, combination treatment of FU and mithramycin A suppressed cell viability even in a gefitinib resistant cell line. CONCLUSIONS: The EGFR signal cascade regulates DPD expression via Sp1 in EGFR mutant cells. These results might be a step towards new therapies targeting Sp1 and DPD in NSCLC with different EGFR mutant status.

Clinicoradiological outcomes of 33 cases of surgically resected pulmonary pleomorphic carcinoma: correlation with prognostic indicators.

OBJECTIVES: To retrospectively review the clinical, radiological and pathological data in patients who underwent surgical resection for pulmonary pleomorphic carcinoma (PC), and to analyse the prognostic predictors of survival. METHODS: The data were retrospectively examined for 33 consecutive patients (28 males and five females) who had undergone surgical resection for pulmonary PC. Cox's proportional-hazards model was used to analyse the prognostic predictors of survival. RESULTS: The size of the tumours ranged from 1.1 to 12.0 cm (mean 5.4 cm). The majority (26) of the tumours were located at the lung periphery, five tumours had cavitation, two had calcification and 14 had peritumoral ground-glass opacity. Most of the tumours showed heterogeneous enhancement and contained a low-density area (LDA) within the tumour. The 5-year overall survival of surgically resected PC was 36 % (standard error = 0.093). A multivariate analysis revealed the LDA grade [hazard ratio (HR), 2.019], pathological stage (HR, 7.552) and pathological N factor (HR, 0.370) to be significant predictors of a poorer prognosis. CONCLUSIONS: A greater component of LDA within the tumour on contrast-enhanced CT is associated with a poorer prognosis in patients with PC. KEY POINTS: PC has a poorer prognosis than other conventional NSCLC. The five-year OS of surgically resected PC was 36 %. A greater component of LDA on contrast-enhanced CT suggests a poorer prognosis.

Prognostic Impact of the ABCC11/MRP8 Polymorphism in Adjuvant Oral Chemotherapy with S-1 for Non-Small Cell Lung Cancer.

BACKGROUND: Postoperative 1-year administration of S-1, an oral derivative of 5-fluorouracil (5-FU), was shown to be feasible in lung cancer. The 5-year survival rates of postoperative patients treated with S-1 adjuvant chemotherapy and the prognostic impact of clinicopathological factors were examined. METHODS: The data of 50 patients with curatively resected pathological stage IB to IIIA non-small cell lung cancer, who were treated with S-1 postoperatively, were analyzed. The prognostic impacts of 22 clinicopathological factors including expressions of the 5-FU pathway enzymes were evaluated. A single-nucleotide polymorphism (SNP), i.e. 538G>A (rs17822931), of ABCC11/MRP8, which encodes a 5-FU excretion enzyme that is known as an earwax type determinant, was also evaluated. RESULTS: The 5-year overall and relapse-free survival rates were 72.5 and 67.5%, respectively. A performance status ≥ 1, lymphatic vessel invasion, blood vessel invasion, and the A/A type of SNP538, which is responsible for the dry earwax type, were significantly associated with shorter relapse-free survivals. In 34 patients who showed a relative performance of 70% or more for chemotherapy, multivariate survival analysis indicated significant hazard ratios only for the A/A type of SNP538 (p = 0.007). CONCLUSIONS: S-1 has sufficient power as adjuvant chemotherapy. However, its effect might be small in the dry earwax type patient group in an adjuvant setting.

Management of unexpected intraoperative bleeding during thoracoscopic pulmonary resection: a single institutional experience.

PURPOSE: Unexpected intraoperative bleeding during thoracoscopic surgery, necessitating emergency conversion to thoracotomy, is gradually being reported. We reviewed our experience of encountering unexpected bleeding during thoracoscopic surgery. METHODS: We defined "unexpected intraoperative bleeding" as the need for hemostatic procedures with angiorrhaphy, with or without a sealant. The location, cause, and management of injured vessels, and perioperative outcomes were investigated and compared with those for patients without injured vessels. RESULTS: Between 2007 and 2014, a total of 241 thoracoscopic anatomical pulmonary resections were performed at our hospital. Twenty (8.3 %) of these patients required hemostatic procedures with angiorrhaphy, with or without a sealant. The main injured vessels were the pulmonary artery (n = 13) and vein (n = 3) and the main causes of injury were related to technical issues with energy devices and staplers. There were no morbidities related to intraoperative bleeding. The operation time and blood loss were significantly greater in the patients with vessel injury than in those without vessel injury, but perioperative morbidities and the duration of chest tube insertion (4.5 vs. 3.5 days, average, p = 0.20) and postoperative hospital stay (12.7 vs. 11.0 days, average, p = 0.08) were not significantly different. CONCLUSIONS: The frequency of unexpected bleeding was relatively high in this series, but its management and outcomes were satisfactory in terms of safety.

[Anastomotic Airway Complications after Lung Transplantation].

Anastomotic airway complications still remain an important issue after lung transplantation. Most of the complications are stenosis and anastomotic leakage. Stent insertion is one option for the stenosis. We review the anastomotic airway complications and report our recent experience of stent insertion using 3-dimensional printed airway model.

Germline mutations causing familial lung cancer.

Genetic factors are important in lung cancer, but as most lung cancers are sporadic, little is known about inherited genetic factors. We identified a three-generation family with suspected autosomal dominant inherited lung cancer susceptibility. Sixteen individuals in the family had lung cancer. To identify the gene(s) that cause lung cancer in this pedigree, we extracted DNA from the peripheral blood of three individuals and from the blood of one cancer-free control family member and performed whole-exome sequencing. We identified 41 alterations in 40 genes in all affected family members but not in the unaffected member. These were considered candidate mutations for familial lung cancer. Next, to identify somatic mutations and/or inherited alterations in these 40 genes among sporadic lung cancers, we performed exon target enrichment sequencing using 192 samples from sporadic lung cancer patients. We detected somatic 'candidate' mutations in multiple sporadic lung cancer samples; MAST1, CENPE, CACNB2 and LCT were the most promising candidate genes. In addition, the MAST1 gene was located in a putative cancer-linked locus in the pedigree. Our data suggest that several genes act as oncogenic drivers in this family, and that MAST1 is most likely to cause lung cancer.

[Perioperative management of primary lung cancer patients with cardiovascular comorbidities].

The number of patients with cardiovascular comorbidities is increasing due to aged society. We evaluated perioperative management of primary lung cancer patients with cardiovascular comorbidities. Between 2010 and 2013, 458 patients underwent lung cancer surgery at out hospital. 60(13%)patients had cardiovascular comorbidities (excluding hypertension and arrhythmia). Forty three(72%) patients were angina pectoris and myocardial infarction, and 7 (12%)were valve disease. In patients with cardiovascular comorbidities, high age, renal dysfunction, low % diffusing capacity for carbon monoxide and limited lymph node dissection were significantly seen. There was one patient with no symptoms of angina with the calcification of coronary artery detected by chest computed tomography(CT)before surgery. Percutaneous coronary artery intervention followed elective lung surgery was successfully performed. Short-term surgical results of patients with cardiovascular comorbidities were acceptable compared to those without.

[Repair of Cardiac and Pulmonary Damage caused by Stabbing with a Kitchen Knife;Report of a Case].

A 51-year-old woman was stabbed in the chest with a kitchen knife. Twenty minutes after arrival at our hospital by ambulance, she was transferred to the operating room, and a cardiopulmonary bypass was established from the right femoral artery and vein, and a median sternotomy was performed. The knife had damaged the surface of the heart and penetrated the lingular segment of the left lung. Both wounds were directly sutured. Chest X-rays taken after closing the chest showed bleeding in the left lung probably because of the administration of heparin. Bleeding was controlled by lingulectomy. The postoperative course was uneventful.

Improvement of Surgical Records and Outcomes after Hepatectomy at a Single Academic Institute in Japan.

BACKGROUND/AIMS: To clarify improvement of hepatic resection in the recent years, we examined surgical records of 544 patients who underwent hepatectomy in 3 periods between 1994 and 2011 at a single academic institute. METHODOLOGY: Subjects were divided into 3 groups: group 1 (1994-1999, n = 156), group 2 (2000-2006, n = 228) and group 3 (2007-2011, n = 160). Clinical factors, surgical records and post-hepatectomy outcomes during hospitalization were compared between groups. RESULTS: In group 3, patient age was significantly higher and the incidences of alcoholic or fatty liver and obstructive jaundice were significantly higher than in group 1 (p < 0.05). Preoperative liver function was not different between groups, and only prothrombin activity was significantly better in group 1 in comparison with the other groups (p < 0.05). In comparison with group 1, the incidence of resident surgeons as the main operator were significantly higher than in group 3 (p < 0.01). Incidences of laparoscopic hepatectomy and thoraco-abdominal approach were increased in group 3 (p < 0.01). Incidences of combined organ and major vessels resections were significantly higher in group 3 in comparison with group 1 (p < 0.01). Use of omental wrapping and hemostatic devices were significantly more frequent in group 3 than in group 1 (p < 0.01). Surgical records were not different between groups but the red cell transfusion rate in group 3 was significantly lower than in group 1 (p < 0.05). Hospital stay in group 3 was significantly shorter than in group 1. Incidence of hepatectomy-related complication, particularly bile leakage, was significantly lower in group 3 than in group 1 (p < 0.05). CONCLUSIONS: According to this evaluation of different time periods, surgical outcomes have been improved with new surgical procedures and perioperative management.

Thoracoscopic versus transsternal resection for early stage thymoma: long-term outcomes.

PURPOSE: This study was undertaken to investigate the efficacy of a video-assisted thoracoscopic (VATS) approach for stage I and II thymoma through comparisons with the transsternal approach. METHODS: The indications for VATS resection were clinical stage I or II thymoma, a tumor less than 50 mm, located within the thymic lobes and separated from the brachiocephalic vein. Data were collected between 1995 and 2007. RESULTS: Twenty-seven patients underwent total thymectomy (15 by VATS and 12 by the transsternal approach). The mean tumor size was 36.3 (22-50) mm for VATS and 37.6 (15-55) mm for the transsternal group (p = 0.7862). The mean lengths of the operation were 249.8 min and 227.9 min (p = 0.2728), respectively. The mean intraoperative blood loss was significantly lower in VATS, at 92.3 ml, than the 225.1 ml lost in the transsternal group (p = 0.0020). The morbidity rates were 13.3 and 8.3% (p = 0.6812), respectively. There was no mortality in either group. The mean follow-up periods were 109.0 (37-145) months following VATS and 102.0 (44-175) months following the transsternal approach. One stage II patient developed pleural dissemination three years after VATS resection. Other patients survived with no recurrence. CONCLUSIONS: VATS resection of early stage thymoma can be performed with less bleeding and with a comparable prognosis to the transsternal approach. VATS resection should thus be considered as a viable option for treatment.