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OBJECTIVES The short-term efficacy of virtual-assisted lung mapping (VAL-MAP), a preoperative bronchoscopic multi-spot lung-marking technique, has been confirmed in 2 prospective multicentre studies. The objectives of this study were to analyse the local recurrence and survival of patients enrolled in these studies, long-term. METHODS Of the 663 patients enrolled in the 2 studies, 559 patients’ follow-up data were collected. After excluding those who did not undergo VAL-MAP, whose resection was not for curative intent, who underwent concurrent resection without VAL-MAP, or who eventually underwent lobectomy instead of sublobar resection (i.e. wedge resection or segmentectomy), 422 patients were further analysed. RESULTS Among 264 patients with primary lung cancer, the 5-year local recurrence-free rate was 98.4%, and the 5-year overall survival (OS) rate was 94.5%. Limited to stage IA2 or less (≤2 cm in diameter; n = 238, 90.1%), the 5-year local recurrence-free and OS rates were 98.7% and 94.8%, respectively. Among 102 patients with metastatic lung tumours, the 5-year local recurrence-free rate was 93.8% and the 5-year OS rate was 81.8%. Limited to the most common (colorectal) cancer (n = 53), the 5-year local recurrence-free and OS rates were 94.9% and 82.3%, respectively. CONCLUSIONS VAL-MAP, which is beneficial in localizing small barely palpable pulmonary lesions and determining the appropriate resection lines, was associated with reasonable long-term outcomes. Subj collection 152, 1542

OBJECTIVES Recent studies have suggested the usefulness of preoperative bronchoscopic marking techniques for the localization of pulmonary nodules in thoracic surgery. This systematic review and meta-analysis aimed to evaluate the efficacy and safety of preoperative bronchoscopic marking. METHODS The PubMed and Cochrane Library databases were searched for clinical studies evaluating preoperative bronchoscopic marking for pulmonary resection. Non-comparative and random effects model-based meta-analyses were conducted to calculate the pooled success and complication rates of bronchoscopic marking. RESULTS Twenty-five eligible studies were included. Among these, 15 studies conducted dye marking under electromagnetic navigation bronchoscopy, 4 used virtual-assisted lung mapping and 7 used other marking methods. The overall pooled successful marking rate, successful resection rate and complete resection rate were 0.97 [95% confidence interval (CI) 0.95–0.99], 0.98 (95% CI 0.96–1.00) and 1.00 (95% CI 1.00–1.00), respectively. The overall pooled rates of pleural injury and pulmonary haemorrhage were 0.02 (95% CI 0.01–0.05) and 0.00 (95% CI 0.00–0.00), respectively. CONCLUSIONS This meta-analysis demonstrated that bronchoscopic marking is very safe and effective. Bronchoscopic marking should be considered, especially if there are concerns about the safety of other localization methods.

The challenges in video-assisted thoracic surgery for sublobar lung resection include difficulty in tumour localization by palpation and difficulty in determining appropriate resection lines. Virtual-assisted lung mapping (VAL-MAP), a bronchoscopic preoperative multispot lung dye-marking technique, allows for both tumour localization and determination of resection lines. To facilitate stapler-based resection, the AMAGAMI or ‘incomplete grasping’ stapler technique is useful to adjust the alignment of the stapler and resection lines. However, when the lung tissue to be stapled is thick, there is unavoidable uncertainty in the staple line inside the lung. We experimentally demonstrated that up to 1 cm of slippage of lung parenchyma occurs at stapling when the stapled lung tissue is >1 cm thick. VAL-MAP 2.0 is a new generation of VAL-MAP combining multispot dye markings with intrabronchial microcoil placement, allowing for 3-dimensional lung mapping and intraoperative navigation using fluoroscopy. The uncertainty of stapling in the lung parenchyma can be partly overcome by VAL-MAP 2.0.

OBJECTIVES Spread through air space (STAS) is recognized as a pattern of invasion in lung adenocarcinoma and has been reported to be a predictor of recurrence and survival in patients with early-stage lung adenocarcinoma. However, this parameter has not been studied well in stage III (N2) lung adenocarcinoma. In this study, we evaluated the association between STAS invasion patterns and recurrence and survival in stage III (N2) lung adenocarcinoma. METHODS We retrospectively reviewed data from 76 patients at University of Tokyo with stage III (N2) lung adenocarcinoma who underwent surgery from August 1998 to December 2013. Statistical analysis was performed to determine the impact of STAS invasion clinicopathological features and clarify the relationship between this pattern of invasion and survival. RESULTS Tumour STAS was observed in 46 of 76 patients (60.5%) and was significantly associated with the presence of lymphatic invasion (P CONCLUSIONS The presence of STAS invasion pattern is a significant risk factor for recurrence in stage III (N2) lung adenocarcinoma.

High shear stress (SS) causes local changes around arterial bifurcations, which are common sites for cerebral aneurysms. High SS and SS spatial gradient (SSG) are thought to play important roles in the pathology of cerebral aneurysms. However, whether SS and SSG independently affect the function and morphology of vascular endothelial cells (ECs) exposed to fluid flow remains unclear. This study evaluated the morphology of ECs exposed to various SS and SSG combinations. Confluent ECs were exposed to a SS of 2–60 Pa and a uniform SSG of 0, 5, 10, or 15 Pa mm−1 for 24 h. Although ECs exposed to lower levels of SS/SSG were not oriented or elongated in the direction of flow, they began to exhibit orientation, elongation, and development of actin stress fibers under the conditions of SS with a SSG when the SS exceeded a threshold value depending on the magnitude of SSG. Using a simplified computational model, we found that the presence of a SSG affects the strain field in ECs, resulting in a morphological response. SS combined with a SSG can alter the localization of SS mechano-sensing proteins along the strain field as a result of shear flow. Our results suggest that the magnitude of the relationship between SS and SSG plays an important role in regulating morphological changes in ECs in response to fluid flow by regulating EC polarity.

Objectives The lung allocation score (LAS) system has been implemented to reduce waiting list time and mortality in the USA, but it remains uncertain how the LAS would reflect the impairment in health-related quality of life (HRQOL), which is another lung transplantation treatment goal to be improved in addition to survival. We thus investigated the relationships of the LAS with mortality and HRQOL in Japanese lung transplantation candidates. Methods One hundred and two candidates for lung transplantation at Kyoto University Hospital between 2009 and 2013 were consecutively recruited to participate in this study. Their physiological measurements of pulmonary function and 6-min walking distance, as well as patient-reported measurements of HRQOL, dyspnoea and psychological status, were assessed. Results Among these 102 patients, 22 died during a mean follow-up of 11.6 months. The LAS was significantly correlated to mortality (P = 0.0026), although other physiological measurements were not. However, regarding its relationship with HRQOL, correlation coefficients between the LAS, Medical Outcomes Study 36-item short form and St George's Respiratory Questionnaire (SGRQ) were relatively low, with the highest at 0.31. Multivariate analyses showed that the LAS was less significantly related to the SGRQ total score than dyspnoea, and psychological status. Conclusions The LAS was significantly related to mortality in lung transplant candidates in Japan, while, despite its multidimensional scoring, its relationship with health-related quality of life was only weak. Their severity assessment system may be more focused on patients' health and symptoms.

Objectives Postoperative myasthenic crisis (POMC) is one of the serious complications after extended thymectomy for patients with myasthenia gravis (MG). This study aims to clarify the risk factors of POMC occurrence. Methods The clinical data of 55 MG patients (25 male, 30 female; median age, 51 years) who underwent extended thymectomy at Kyoto University from 2000 to 2013 were retrospectively reviewed. Surgical outcomes and pre- and perioperative predictive factors of POMC were analysed. Results The preoperative Myasthenia Gravis Foundation of America stage was I, II, III and IV in 24, 22, 8 and 1 patients, respectively. Ten patients (18.2%) developed POMC; 6 required prolonged intubation over 24 h and 4 required reventilatory support. All patients were weaned after 5.6 (2-26) days of ventilator support, and were discharged. Univariate analysis revealed a correlation with a high preoperative anti-acetylcholine receptor antibody titre (P = 0.009), history of myasthenic crisis (MC) (P = 0.0004) and unstable MG after preoperative medical therapy (P = 0.003). Multivariate logistic regression analysis showed history of MC (odds ratio, 11.84; 95% confidential interval, 1.05-372; P = 0.045) and unstable MG (odds ratio, 29.45; 95% confidential interval, 2.00-1063; P = 0.013) independently predicted POMC. The surgical response rate was not significantly different between the two groups (66.7% with POMC, 85.4% without POMC; P = 0.334). Conclusions POMC occurred more frequently in unstable MG before surgery or in patients with a history of MC. Adequate preoperative medical therapy and perioperative care should be provided to these patients.

Living-donor lobar lung transplantation (LDLLT) has been established as a life-saving procedure for critically ill patients who cannot wait for cadaveric lung transplantation. Chronic lung allograft dysfunction (CLAD) is the main cause of late morbidity and mortality in lung transplantation. Studies on CLAD in cadaveric lung transplantation have been extensively reported, but few reports have been reported concerning CLAD after LDLLT. The aim of this study was to determine the prevalence, characteristics and prognosis of CLAD after LDLLT.Among 38 patients who survived more than 3 months after LDLLT at Kyoto University Hospital between June 2008 and December 2013, 8 patients (21%) were diagnosed with CLAD. The mean follow-up period after LDLLT was 33 months. Clinical course, pulmonary function and radiological findings were reviewed retrospectively in all the 38 patients as of May 2014.Six patients were female and 2 were male. The median age at LDLLT was 31 years, and the median interval between LDLLT and the initial diagnosis of CLAD was 23 months. Among 8 patients who developed CLAD, 2 patients underwent right single LDLLT and 6 patients underwent bilateral LDLLT. The former 2 patients survived 44 and 47 months after the treatment. Five out of 6 patients with bilateral LDLLT developed unilateral CLAD at the time of initial diagnosis according to ventilation scintigraphy. In 3 of these 5 patients, the progression of CLAD was halted by treatment, and the median follow-up period of 33 months after treatment. In the remaining 2 of 5 patients, CLAD progressed to the contralateral lung metachronously; 1 patient survived without oxygen supplement, but the other patient required reperformance of LDLLT 3 years after the first one. One patient with bilateral CLAD at the time of detection died of disease progression 4 years after LDLLT.Despite a relatively short observation time, CLAD developed in approximately one-fifth of the patients who survived more than 3 months after LDLLT. In bilateral LDLLT, CLAD developed unilaterally in most cases, which might be beneficial in the long term because the unaffected contralateral lung may function as a reservoir.

OBJECTIVES: Living-donor lobar lung transplantation (LDLLT) has been performed as a life-saving procedure for critically ill patients who are unlikely to survive the long wait for cadaveric lungs. The purpose of this study was to compare the preoperative condition and outcome of LDLLT patients with those of conventional cadaveric lung transplantation (CLT) patients. METHODS: A new lung transplant programme was established in 2008 at Kyoto University. Between June 2008 and January 2014, we performed 79 lung transplants, including 42 LDLLTs (10 single, 32 bilateral) and 37 CLTs (22 single, 15 bilateral). Data collected included preand perioperative variables and mid-term survival. All data were analysed retrospectively as of January 2014. RESULTS: The majority of patients were female (57.1%) in the LDLLT group and male (64.9%) in the CLT group. The average age was similar (36.6 ± 20.7 vs 39.7 ± 12.6 years, P= 0.42) between the two groups. Preoperatively, interstitial lung disease was more common in LDLLT patients than in CLT patients (47.6 vs 24.3%, P= 0.048); prior haematopoietic stem cell transplantation was performed more often in LDLLT patients than in CLT patients (33.3 vs 13.5%, P= 0.040) and there were more steroid-dependent LDLLT patients than CLT patients (64.3 vs 29.7%, P= 0.0022). Based on preoperative criteria of lower body mass index (17.2 ± 4.0 vs 19.3 ± 3.3 kg/m 2 , P= 0.013), less ambulatory ability (42.9 vs 86.5%, P= 0.0001) and more ventilator dependence (11.9 vs 2.7%, P= 0.12), LDLLT patients were more debilitated than CLT patients. LDLLT patients required longer postoperative mechanical ventilation than CLT patients (15.6 ± 16.2 vs 8.5 ± 8.1 days, P= 0.025). However, 1- and 3-year survival rates were similar between the two groups (89.7 and 86.1% vs 88.3 and 83.1%, P= 0.55). All living donors returned to their previous lifestyles without restriction. CONCLUSIONS: Although LDLLT patients were in a worse preoperative condition than CLT patients, LDLLT patients demonstrated survival rates similar to CLT patients. LDLLT is a viable option for patients too ill to survive a long waiting time for cadaveric donors.

OBJECTIVES: Recent studies suggest hypogammaglobulinemia (HGG) is frequently associated with infection after solid organ transplantation, although the effects of HGG after lung transplantation are not well recognized. We investigated the incidence and degree of HGG after lung transplantation and its association with infection. METHODS: A retrospective cohort study analysing pre- and post-transplant IgA, IgG and IgM levels and infectious events in patients undergoing living-donor lobar and cadaveric lung transplantation at Kyoto University Hospital between June 2008 and March 2013. RESULTS: Overall, post-transplant immunoglobulin (Ig) levels were significantly lower than pretransplant levels. In almost all patients who received transplants for bronchiolitis obliterans (BO) after haematopoietic stem cell transplantation (HSCT), interstitial lung diseases and bronchiectasis, post-transplant IgA and IgG levels decreased and were significantly lower than pretransplant levels; pre- and post-transplant IgA and pretransplant IgG levels were significantly lower in patients transplanted for BO after HSCT than in the others. Post-transplant IgG levels in patients transplanted for BO after HSCT also tended to be lower than those in the others, but not significantly. Nineteen of 29 patients had HGG after lung transplantation (65.5%) and had more infections than the normal gammaglobulinemia group, although there was no significant difference. Among them, 2 patients transplanted for BO after HSCTwith quite low HGG had severe pneumonia and finally died. CONCLUSIONS: Post-transplant Ig levels were significantly lower than pretransplant levels. Although without significant difference, HGG patients had more infections, above all, those with severe HGG transplanted for BO after HSCT could have lethal infections. Ig levels in HGG should be monitored carefully because severe HGG was associated with poor prognosis.

The purpose of the study reported in this article was to investigate effects of synthetic lipid A on the expression of adhesion molecule CD44 on bovine articular chondrocytes. Full-thickness bovine articular cartilage was dissected from the carpometacarpal joints of 24 cows. Cartilage pieces were enzymatically digested to liberate chondrocytes. The chondrocytes were incubated in the presence of synthetic lipid A in suspension culture. Cell characteristics and binding of monoclonal antihuman CD44 antibodies were assessed with a flow cytometer. The expression of CD44 mRNA in chondrocytes was detected by reverse transcription-polymerase chain reaction (RT-PCR) technique. PCR products were quantified with a charge-coupled device image sensor. The percentage of CD44-positive chondrocytes was 42.2% ± 12.0%, 51.7% ± 6.8%, and 51.1% ± 5.0%, in the presence of lipid A at 0.25 μg/ml, 2.5 μg/ml, and 25 μg/ml, respectively, whereas it was 39.2% ± 8.9% in the absence of lipid A. In flow cytometry, two subpopulations of chondrocytes were found in each of five separate experiments, one with smaller number of forward scatter (FS) and the other with larger number of FS. The percentage of CD44-positive cells was 24.8% ± 8.5% in the subpopulation with smaller number of FS and 31.9% ± 6.4% in the subpopulation with larger number of FS at time 24 h after incubation. The bacterial component, lipid A, upregulated expression of CD44 on articular chondrocytes.

OBJECTIVES: Virtual-assisted lung mapping (VAL-MAP) is a preoperative bronchoscopic multispot dye-marking technique using virtual images. The purpose of this study was to evaluate the safety, efficacy and reproducibility of VAL-MAP among multiple centres. METHODS: Selection criteria included patients with pulmonary lesions anticipated to be difficult to identify at thoracoscopy and/or those undergoing sub-lobar lung resections requiring careful determination of resection margins. Data were collected prospectively and, if needed, compared between the centre that originally developed VAL-MAP and 16 other centres. RESULTS: Five hundred patients underwent VAL-MAP with 1781 markings (3.6 ± 1.2 marks/patient). Complications associated with VAL-MAP necessitating additional management occurred in four patients (0.8%) including pneumonia, fever and temporary exacerbation of pre-existing cerebral ischaemia. Minor complications included pneumothorax (3.6%), pneumomediastinum (1.2%) and alveolar haemorrhage (1.2%), with similar incidences between the original centre and other centres. Marks were identifiable during operation in approximately 90%, whereas the successful resection rate was approximately 99% in both groups, partly due to the mutually complementary marks. The contribution of VAL-MAP to surgical success was highly rated by surgeons resecting pure ground glass nodules (P

The tryptic digestion of beta-conglycinin was studied by the pH-stat method and sodium dodecyl sulfate gel electrophoresis. The proteolysis of the protein was not affected by the change of ionic strength. This property was distinct from that of glycinin which is degraded rapidly at a low ionic strength.Five stable fragments were generated in the degradation course. Two kinds of beta-conglycinin, one of which consisted of only the beta-subunit and the other of only the alpha’ and alpha-subunit, were isolated to elucidate the original subunit of the fragments. Two fragments (AT-1 and AT-2) from the alpha’ and alpha-subunit, and three fragments (BT-2-BT-4) from the beta-subunit were generated. The molecular weights of the fragments were similar to those of the glycinin fragments. From the fragment pattern of the beta-subunit, the presence of two types of the beta-subunit was expected.

A new type of β-conglycinin was found in precipitates of a crude glycinin fraction at pH 6.4 and low ionic strength. The protein was purified by ammonium sulfate fractionation, Con A-Sepharose 4B affinity chromatography and ion-exchange chromatography on DEAE-Sepharose CL-6B. The purity check and identification of the protein were performed by gel electrophoresis, gel filtration, N-terminal amino acid analysis, immunochemical analysis and ultra-centrifugal analysis. This protein (designated as B0-conglycinin) was composed of three identical subunits which were identical with the β-subunit in β-conglycinins at 0.5 ionic strength, but differed from the other β-conglycinins in that B0-conglycinin formed an insoluble aggregate at ionic strengths less than 0.2.