Masatsugu Hamaji

Comparison of long-term survival outcomes between stereotactic body radiotherapy and sublobar resection for stage i non-small-cell lung cancer in patients at high risk for lobectomy: A propensity score matching analysis

BACKGROUND The aim of this study was to perform a survival comparison between stereotactic body radiotherapy (SBRT) and sublobar resection (SLR) in patients with stage I non-small-cell lung cancer (NSCLC) at high risk for lobectomy. METHODS All patients who underwent SBRT or SLR because of medical comorbidities for clinical stage I NSCLC were reviewed retrospectively. Propensity score matching (PSM) was performed to reduce selection bias between SLR and SBRT patients based on age, gender, performance status, tumour diameter, forced expiratory volume in 1 second (FEV1) and Charlson comorbidity index (CCI). RESULTS One hundred and fifteen patients who underwent SBRT and 65 SLR were enrolled. The median potential follow-up periods for SBRT and SLR were 6.7 and 5.3 years, respectively. No treatment-related deaths were observed. Before PSM, the 5-year overall survival (OS) was 40.3% and 60.5% for SBRT and SLR, respectively (P=0.008). PSM identified 53 patients from each treatment group with similar characteristics: a median age of 76 years, a performance status of 0-1, a median tumour diameter of ∼20 mm, a median FEV1 of ∼1.8L and a median CCI of 1. The difference in OS became insignificant between the matched pairs (40.4% and 55.6% at 5 years with SBRT and SLR; P=0.124). The cumulative incidence of cause-specific death was comparable between groups (35.3% and 30.3% at 5 years, P=0.427). CONCLUSION SBRT can be an alternative treatment option to SLR for patients who cannot tolerate lobectomy because of medical comorbidities.

Reinforced closure of the sternum with absorbable pins for high-risk patients

We report our result of the reinforced sternal closure in 51 consecutive patients. We applied a new type of absorbable radiopaque pins (Super FIXSORB) composed of poly-lactide acid and hydroxyapatite, in addition to conventional stainless steel wires. The risk scores of our patients were calculated from the simplified risk scoring system for major infection based on the Society of Thoracic Surgeons National Cardiac Database. The expected probability of infection is significantly higher than the actual infection rate in our patients. Our procedure may contribute to minimizing the fatal sternal complication particularly in high-risk patients.

Treatment and Prognosis of Isolated Local Relapse after Stereotactic Body Radiotherapy for Clinical Stage I Non-Small-Cell Lung Cancer Importance of Salvage Surgery

Introduction: Many efforts have been made to detect local relapse (LR) in the follow-up after stereotactic body radiotherapy (SBRT) for non–small-cell lung cancer (NSCLC) although limited data are available on its treatment and prognosis. We aimed to characterize treatment options and clarify long-term outcomes of isolated LR after SBRT for patients with clinical stage I NSCLC. Methods: We reviewed our institutional database in search of patients with isolated LR after SBRT for clinical stage I NSCLC at our institution between 1999 and 2013. Patient characteristics were compared with Mann–Whitney U test, &khgr;2 test, or Fisher’s exact test as appropriate. Survival outcomes were estimated with Kaplan–Meier method. Potential prognostic factors were investigated using Cox proportional hazard model. Results: Of 308 patients undergoing SBRT for clinical stage I NSCLC, 49 patients were identified to have isolated LR. Twelve patients underwent salvage surgery, none underwent radiotherapy, and eight patients received chemotherapy, whereas 29 patients received best supportive care. No patient characteristic except operability was significantly related with patient selection for LR treatments. Five-year overall survival (OS) rate of the whole cohort was 47.9% from SBRT and 25.7% from LR. Salvage surgery was associated with improved OS after LR (p = 0.014), and 5-year OS for patients undergoing salvage surgery was 79.5% from LR. Conclusions: It was confirmed that our patient selection for salvage surgery for isolated LR was associated with favorable survival outcomes. Operability based on multidisciplinary conferences, rather than measurable patient characteristics, is essential for appropriate patient selection for salvage surgery.

A meta-analysis of surgical versus nonsurgical management of recurrent thymoma.

This meta-analysis was designed to determine the effect of surgical and nonsurgical approaches on 5-year and 10-year overall survival (OS) in patients with recurrent thymoma. PubMed, Scopus, and the Journal of Japanese Association for Chest Surgery were queried, and 11 studies were eligible. Our meta-analysis using a random-effect model revealed significant differences in the rates of 5- and 10-year OS after thymectomy and in 5-year OS after recurrence, favoring surgically managed patients. Surgical resection may be associated with improved long-term survival and should be considered for patients with recurrent thymoma.

A meta-analysis of debulking surgery versus surgical biopsy for unresectable thymoma

Observational studies on long-term outcomes following debulking surgery or surgical biopsy for unresectable thymoma showed various results. This meta-analysis was designed to determine the effect of debulking surgery against surgical biopsy on overall survival in patients with unresectable thymoma. The PubMed database was queried for studies published in the English language on unresectable thymoma and overall survival. We compared overall survival following surgery in patients undergoing debulking surgery and patients undergoing surgical biopsy for unresectable thymoma. Meta-analysis was performed using the Mantel-Haenszel method, and potential publication bias was evaluated with a funnel plot of precision. No randomized trials on this topic were identified. Thirteen retrospective observational studies containing a sum of 314 patients with information on the number of deaths and person-years were suitable for analysis. Information on Masaoka stages, World Health Organization histology and indications for debulking surgery versus surgical biopsy was lacking in most studies. Diversity of neoadjuvant and adjuvant treatments was noted among the eligible studies. One hundred and seventy-two (54.8%) patients underwent debulking surgery and 142 (45.2%) underwent surgical biopsy. The pooled hazard ratio was 0.451 (95% confidence interval: 0.336-0.605, P < 0.001), favouring patients undergoing debulking surgery compared with patients undergoing surgical biopsy. The funnel plot of precision demonstrated no important publication bias. Our results suggest that debulking surgery for unresectable thymoma may be associated with improved overall survival and be considered for patients with unresectable thymoma.

A Meta-Analysis of Resected Metachronous Second Non-Small Cell Lung Cancer

This meta-analysis was designed to determine the effect of surgical treatment on overall survival of patients treated surgically for a second non-small cell lung cancer (NSCLC) that occurred after resection of an initial NSCLC. PubMed and Scopus databases were queried. Nine studies were identified. Meta-analyses revealed pooled operative mortality of 7% for the second resection, pooled 5-year overall survival of 46% after resection of the second NSCLC, and 79% after resection of the first NSCLC. These results suggest that surgical resection can be considered for patients who have a second primary NSCLC after resection of an initial lung cancer.

Genomic Analysis of Thymic Epithelial Tumors Identifies Novel Subtypes Associated with Distinct Clinical Features.

Purpose: To reconcile the heterogeneity of thymic epithelial tumors (TET) and gain deeper understanding of the molecular determinants of TETs, we set out to establish a clinically relevant molecular classification system for these tumors. Experimental Design: Molecular subgrouping of TETs was performed in 120 patients from The Cancer Genome Atlas using a multidimensional approach incorporating analyses of DNA mutations, mRNA expression, and somatic copy number alterations (SCNA), and validated in two independent cohorts. Results: Four distinct molecular subtypes of TETs were identified. The most commonly identified gene mutation was a missense mutation in General Transcription Factor II-I (GTF2I group), which was present in 38% of patients. The next group was identified by unsupervised mRNA clustering of GTF2I wild-type tumors and represented TETs enriched in expression of genes associated with T-cell signaling (TS group; 33%). The remaining two groups were distinguished by their degree of chromosomal stability (CS group; 8%) or instability (CIN group; 21%) based upon SCNA analyses. Disease-free survival and overall survival were favorable in the GTF2I group and unfavorable in the CIN group. These molecular subgroups were associated with TET histology and clinical features including disease-free survival. Finally, we demonstrate high expression of PD1 mRNA and correlation of PD1 and CD8A in the TS subgroup. Conclusions: Molecular subtyping of TETs is associated with disease-free and overall survival. Classification of TETs by a molecular framework could aid in the refinement of staging and in the discovery and development of rational treatment options for patients with TETs. Clin Cancer Res; 23(16); 4855–64. ©2017 AACR.

Development of a composite and vascularized tracheal scaffold in the omentum for in situ tissue engineering: a canine model

OBJECTIVES We herein report on development of a composite (synthetic and biological) tracheal scaffold with vascularized autologous connective tissue in the omentum, followed by in situ tissue engineering of the composite scaffold with the pedicled omentum. In this preliminary report, we focus on development and evaluation of the vascularized autologous connective tissue in the omentum. METHODS In animal experiment 1, a polypropylene framework as a synthetic component was placed in the omental sac for 3 weeks and another was placed in the pouch of Douglas as a control in five beagle dogs. In animal experiment 2, a polypropylene framework placed in the omental sac for 3 weeks was compared with a polypropylene framework coated with porcine atelocollagen, which was also placed in the omental sac in another five dogs, to investigate whether the coating of porcine atelocollagen contributes to development of more vascularized connective tissue. Macroscopic, radiological and histological evaluations were performed for developed autologous connective tissue on the frameworks, with a focus on its thickness and capillary vessels. RESULTS In animal experiment 1, the polypropylene framework in the omentum developed a composite tracheal scaffold with homogeneous and significantly thicker (2.6 ± 0.5 vs 1.2 ± 0.4 mm, P <0.0001) connective tissue in which more capillary vessels per 10-power field of view (3.5 ± 2.2 vs 0 ± 0, P = 0.015) were identified, compared with the control in the pouch of Douglas. In animal experiment 2, the omentum developed significantly thicker connective tissue on the polypropylene framework coated with porcine atelocollagen (3.6 ± 0.7 vs 2.2 ± 0.4 mm, P <0.0001) in which not significantly more capillary vessels were identified (3.5 ± 2.2 vs 5.0 ± 2.7, P = 0.12), compared with the framework that was not coated. CONCLUSIONS Placement of the polypropylene framework in the omental sac resulted in development of homogeneous and vascularized autologous connective tissue on the polypropylene framework for a composite tracheal scaffold. The framework coated with porcine atelocollagen did not show an additional benefit in inducing vascularization. This preliminary report will be followed by the long-term evaluations of in situ tissue engineering of the composite tracheal scaffold.

A synthetic bioabsorbable sheet may prevent postoperative intrapleural adhesions following thoracotomy: a canine model

OBJECTIVES Intrapleural adhesions following thoracotomy may be associated with prolonged operating time or a higher complication rate at reoperation. The aim of this experimental study was to investigate the anti-adhesion property of a bioabsorbable sheet following thoracotomy in a canine model. METHODS Ten adult beagle dogs underwent bilateral muscle-sparing thoracotomies with single ribs resected under general anaesthesia. A bioabsorbable sheet composed of poly-L-lactide copolymer (45 wt%) and ε-caprolactone (45 wt%) layered with polyglycolic acid (10 wt%) was sutured intrapleurally on the parietal pleura to cover the defect on the left, but not placed on the right side as a control. All the dogs were followed up with chest computed tomography until being sacrificed (6 months at the maximum). Thoracoscopic evaluations were performed at 1, 3 and 6 months for intrapleural adhesions at the thoracotomy site and absorption of the bioabsorbable sheet. The incidences of intrapleural adhesions were compared between the experimental side and the control side by the χ(2) test. Histological (macroscopic and microscopic) analyses of regenerated chest wall tissue were also performed at 1, 3 and 6 months. RESULTS All the dogs survived uneventfully until being sacrificed without any postoperative complications or significant radiological findings. The bioabsorbable sheet prevented intrapleural adhesions in all subjects. There were statistically significant differences in the incidence of intrapleural adhesions between the experimental side and the control side at the thoracotomy incision (0 vs 80%, P = 0.0014) at 1 month, (0 vs 66.7%, P = 0.014) at 3 months and (0 vs 75%, P = 0.028) at 6 months. The bioabsorbable sheet was found residual at 1, 3 and 6 months in all subjects. Histological analyses confirmed regenerated chest wall layers with significantly more capillary vessels at 1 month (P = 0.015), but not at 3 and 6 months (P = 0.84 and 0.41, respectively), in the regenerated mucosal and submucosal layers on the experimental side. CONCLUSIONS Our findings suggest that the bioabsorbable sheet may prevent intrapleural adhesions with parietal pleurae regenerated with more vascularization at 1 month following thoracotomy. No adverse findings were noted with the sheet.

Survival and treatments in patients with incompletely resected thymoma

Objectives the objective of our study was to clarify survival and treatments in patients with incompletely resected thymoma. Methods between January 1991 and December 2012, 156 consecutive patients who underwent thymectomy with curative intent at Kyoto University Hospital, were evaluated retrospectively. Overall survival and progression-free survival were analyzed using the Kaplan-Meier method, comparing the complete resection group (n = 141) with the incomplete resection group (n = 15). Potentially relevant factors for overall survival and progression-free survival in patients with incompletely resected thymomas were analyzed using Cox proportional-hazard models. Results there was a significant difference in progression-free survival (p = 0.0012) but not in overall survival (p = 0.638) following thymectomy in the complete and incomplete resection groups. Adjuvant chemotherapy was performed in 6 (40%) patients and adjuvant radiotherapy in 6 (40%) in the incomplete resection group. In univariate analysis, younger age (p = 0.073) showed a tendency for better overall survival, and adjuvant chemotherapy (p = 0.071) showed a tendency for better progression-free survival. Conclusion our results suggest that patients with incompletely resected thymomas can achieve comparable overall survival to those with completely resected thymomas. Adjuvant chemotherapy for incompletely resected thymomas tends to improve progression-free survival.