記述言語：英語   出版者・発行元：Annals of Surgical Oncology  

Objectives: The rates of postoperative mortality and morbidity are high in patients with malignant pleural mesothelioma (MPM). Therefore, it is important to identify variables that increase the risk of postoperative complications. Pleural thickness has recently been identified as a prognostic indicator in patients with MPM. The aim of this study was to investigate clinical variables, including pleural thickness, that contribute to postoperative complications in patients with MPM. Patients and Methods: A total of 47 patients who underwent surgical excision of MPM between 2005 and 2021 were enrolled in this study. Correlations between postoperative complications within 90 days of surgery and preoperative clinical factors were investigated. Results: A total of 27 patients underwent extrapleural pneumonectomy (EPP), and the remaining 20 underwent pleurectomy/decortication (P/D). Macroscopic complete resections were obtained in all but three patients. Of the 47 patients, 23 (49%) experienced postoperative complications of grade 3 or worse. The major complication in patients with EPP was respiratory failure (n = 6), whereas the major complication in patients with P/D was prolonged air leakage (n = 7). Univariate logistic regression analysis found a correlation between postoperative complications and age, surgical side, and pleural thickness, while multivariate logistic regression analysis found surgical side (p = 0.04, 95% Cl 1.10–21.71, OR 4.90) and pleural thickness (p = 0.03, 95% Cl 1.21–23.00, OR 5.26) to significantly influence the occurrence of postoperative complications. Conclusions: Pleural thickness has a significant effect on the occurrence of postoperative complications. Patients with thick pleura on the right side are at greater risk of postoperative complications.

DOI： 10.1245/s10434-022-12790-9

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記述言語：英語   出版者・発行元：Anticancer Research  

Background/Aim: Multidisciplinary treatment including anatomical pulmonary and chest wall resection is recommended for lung cancer complicated by chest wall invasion. The present study aimed to investigate the survival benefit and safety of preoperative therapy followed by surgery for non-small cell lung cancer with chest wall invasion. Patients and Methods: Sixty-five patients who underwent surgical excision of lung cancer complicated with chest wall invasion between 2009 and 2020 were enrolled in this study. Results: The median age was 65 (37-81) years old, with 59 males and 6 females. Histological types included squamous cell carcinoma (n=32) and adenocarcinoma (n=21). The median tumor diameter was 5.5 cm (2.3-12.5 cm). The clinical nodal status was N0 in 49 cases and N positive in 16 cases. Of the 65 eligible patients, 5- and 10-year overall survival (OS) rates were 58.4% and 46.0%, respectively, and 5- and 10-year progression-free survival (PFS) rates were 54.2% and 41.7%, respectively. For patients receiving preoperative therapy followed by surgery (Pre-Tx), 5- and 10-year OS survival rates were 69.2% and 62.9%, and among patients receiving up-front surgery (UFS) were 48.5% and 29.1%, respectively (p=0.03). The 5- and 10-year PFS rates for pre-Tx were 65.8% and 59.2%, respectively, and 44.7% and 26.8% for UFS, respectively (p=0.02). Cox regression analysis preoperative therapy was significantly associated with OS and PFS. Conclusion: We demonstrate the survival benefit of preoperative therapy followed by surgery for patients with lung cancer and chest wall invasion.

DOI： 10.21873/anticanres.16059

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記述言語：英語   出版者・発行元：International Journal of Molecular Sciences  

There is substantial interest in mining neoantigens for cancer applications. Non-canonical proteins resulting from frameshift mutations have been identified as neoantigens in cancer. We investigated the landscape of non-canonical proteins in non-small cell lung cancer (NSCLC) and their induced immune response in the form of autoantibodies. A database of cryptoproteins was computationally constructed and comprised all alternate open reading frames (altORFs) and ORFs identified in pseudogenes, noncoding RNAs, and untranslated regions of mRNAs that did not align with known canonical proteins. Proteomic profiles of seventeen lung adenocarcinoma (LUAD) cell lines were searched to evaluate the occurrence of cryptoproteins. To assess the immunogenicity, immunoglobulin (Ig)-bound cryptoproteins in plasmas were profiled by mass spectrometry. The specimen set consisted of plasmas from 30 newly diagnosed NSCLC cases, pre-diagnostic plasmas from 51 NSCLC cases, and 102 control plasmas. An analysis of LUAD cell lines identified 420 cryptoproteins. Plasma Ig-bound analyses revealed 90 cryptoproteins uniquely found in cases and 14 cryptoproteins that had a fold-change >2 compared to controls. In pre-diagnostic samples, 17 Ig-bound cryptoproteins yielded an odds ratio ≥2. Eight Ig-bound cryptoproteins were elevated in both pre-diagnostic and newly diagnosed cases compared to controls. Cryptoproteins represent a class of neoantigens that induce an autoantibody response in NSCLC.

DOI： 10.3390/ijms23168933

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記述言語：英語  

DOI： 10.3390/cancers13184604

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記述言語：英語  

DOI： 10.3390/cancers13163972

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記述言語：英語  

DOI： 10.3390/cells9061518

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記述言語：日本語  

DOI： 10.3390/cancers12051147

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記述言語：日本語  

DOI： 10.1053/j.semtcvs.2019.09.002

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記述言語：英語   出版者・発行元：Nagoya journal of medical science  

There is little known about predictors of the effects of induction therapy in locally advanced lung cancer, including superior sulcus tumors. We analyzed whether intra-tumoral blood feeding could predict a pathologic complete response (pCR). Patients who underwent induction therapy followed by surgery for locally advanced lung cancer were retrospectively reviewed. The intra-tumoral blood feeding was defined by the CT value (HU, Hounsfield unit), which was calculated by subtracting the non-enhanced value from the contrast-enhanced value (divided into the early and delayed phase) at the maximum diameter of the tumor on dynamic CT. The cases were classified, according to the efficacy of induction therapy, into the pCR and residual tumor (pRT) group. There were 38 cases of T3 and 12 of T4; the induction therapy consisted of chemoradiotherapy in 39 patients, chemotherapy in 6, and radiotherapy in 5. A pCR was obtained in 15 (30%) patients. The mean CT values of the early and delayed phases in the pCR group were 14.8 and 30.7 HU, while those in the pRT were 15.3 and 32.2 HU, respectively. A logistic regression analysis revealed that a smaller tumor size (< 42 mm) was a non-significant predictor of a pCR (p = 0.09); the maximum standardized uptake value on FDG-PET and the CT values on the early and delayed phases of dynamic CT were not associated with the achievement of a pCR. In conclusion, intra-tumoral blood feeding of the locally advanced lung cancer did not predict the effects of induction therapy, whereas smaller sized tumors tended to show a better response.

DOI： 10.18999/nagjms.81.2.291

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記述言語：英語   出版者・発行元：Annals of Thoracic Surgery  

Background: Programmed death ligand 1 (PD-L1) is reportedly expressed in various malignancies and is considered a prognostic factor. We attempted to reveal the usefulness of the PD-L1 expression as a prognostic factor in patients with thymoma. Methods: Eighty-one patients with thymoma who underwent surgical resection between 2004 and 2015 were retrospectively reviewed. The PD-L1 expression was evaluated by immunohistochemistry and stratified by the proportion of positive tumor cells. Strong membranous reactivity of the PD-L1 antibody in 1% or more of tumor cells was considered “positive.” The association between the PD-L1 expression and the clinicopathologic features was investigated. Results: The PD-L1 expression was positive in 22 patients (27%) and negative in 59 patients (73%). The PD-L1 positivity was significantly associated with type B2 and B3 thymoma (p < 0.001) and stage III and IV disease (p = 0.048). In addition, PD-L1 positive tumors showed a significantly higher maximum standardized uptake value than PD-L1 negative tumors (p = 0.026). The 5-year disease-free survival rate was 82% in PD-L1 positive patients and 88% in PD-L1 negative patients, showing no significant difference (p = 0.57). Furthermore, PD-L1 positivity was not an independent prognostic factor for the disease-free survival on a Cox proportional hazards analysis (p = 0.59). Conclusions: A strong expression of PD-L1 in thymoma was significantly associated with type B2 and B3 and higher pathologic stages. In addition, PD-L1 positivity was associated with an increased maximum standardized uptake value of the tumor. However, patients with PD-L1 positive thymomas did not show a significantly worse prognosis than patients with PD-L1 negative tumors.

DOI： 10.1016/j.athoracsur.2018.08.037

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記述言語：日本語  

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記述言語：英語   出版者・発行元：International Journal of Clinical Oncology  

Background: Differences in individual body sizes have not been well considered when analyzing the survival of patients with non-small cell lung cancer (NSCLC). We hypothesized that physique-adjusted tumor size is superior to actual tumor size in predicting the prognosis. Methods: Eight hundred and forty-two patients who underwent R0 resection of NSCLC between 2005 and 2012 were retrospectively reviewed, and overall survival (OS) was evaluated. The physique-adjusted tumor size was defined as: x-adjusted tumor size = tumor size × mean value of x/individual value of x [x = height, weight, body surface area (BSA), or body mass index (BMI)]. Tumor size category was defined as ≤2, 2–3, 3–5, 5–7, and >7 cm. The separation index (SEP), which is the weighted mean of the absolute value of estimated regression coefficients over the subgroups with respect to a reference group, was used to measure the separation of subgroups. Results: The mean values of height, weight, BSA, and BMI were 160.7 cm, 57.6 kg, 1.59 m2, and 22.2 kg/m2, respectively. The 5-year survival rates ranged from 88−59% in the non-adjusted tumor size model (SEP 1.937), from 90−57% in the height-adjusted model (SEP 2.236), from 91−52% in the weight-adjusted model (SEP 2.146), from 90−56% in the BSA-adjusted model (SEP 2.077), and from 91−51% in the BMI-adjusted model (SEP 2.169). Conclusions: The physique-adjusted tumor size can separate the survival better than the actual tumor size.

DOI： 10.1007/s10147-017-1219-6

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記述言語：日本語  

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記述言語：日本語  

DOI： 10.1093/ejcts/ezx124

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記述言語：日本語  

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記述言語：日本語  

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記述言語：英語   出版者・発行元：General Thoracic and Cardiovascular Surgery  

Objectives: The aim of this study was to investigate the feasibility and safety of our surgical experiences conducted in collaboration with cardiovascular surgeons at our institution. Methods: From May 2002 to December 2015, among 3595 general thoracic surgeries, 75 (2.1%) operations were carried out collaboratively with cardiovascular surgeons at Nagoya University Hospital. We investigated the surgical procedures, manipulated organs, morbidity and mortality, completeness of surgical resection, and prognosis of these 75 cases. Results: The study cohort consisted of 56 males and 19 females, ranging in age from 18 to 79 years (median 60 years). Fifty-eight patients had a malignant disease, and 17 had a benign disease. Out of 75 collaborative surgeries, 53 (71%) were scheduled cases (cardiovascular surgeons’ support was considered to be necessary preoperatively), and 22 (29%) were emergent cases (cardiovascular surgeons’ support was considered to be necessary intraoperatively). No 30- or 90-day mortality was observed. Respiratory failure, defined as the requirement of mechanical ventilation or non-invasive positive pressure ventilation for ≥5 days, was the most common morbidity (n = 14, 18%). Forty-three patients (78%) out of 55 with thoracic neoplasms achieved microscopic complete resection. The resection status of the remaining 12 (22%) was microscopic residual tumor. Conclusion: Collaborative surgeries with cardiovascular surgeons at our institution were feasible. High-quality surgeries with a good balance between safety and completeness of resection are important not only for treatment, but also in terms of education for general thoracic surgeons.

DOI： 10.1007/s11748-017-0800-2

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記述言語：英語   出版者・発行元：Oncogene  

Malignant mesothelioma (MM) is an aggressive tumor commonly caused by asbestos exposure after a long latency. Focal adhesion kinase (FAK) inhibitors inhibit the cell growth of Merlin-deficient MM cells; however, their clinical efficacy has not been clearly determined. The aim of this study was to evaluate the growth inhibitory effect of the FAK inhibitor VS-4718 on MM cell lines and identify biomarkers for its efficacy. Although most Merlin-deficient cell lines were sensitive to VS-4718 compared with control MeT-5A cells, a subset of these cell lines exhibited resistance to this drug. Microarray and qRT-PCR analyses using RNA isolated from Merlin-deficient MM cell lines revealed a significant correlation between E-cadherin mRNA levels and VS-4718 resistance. Merlin- and E-cadherin-negative Y-MESO-22 cells underwent apoptosis upon treatment with a low concentration of VS-4718, whereas Merlin-negative, E-cadherin-positive Y-MESO-9 cells did not undergo VS-4718-induced apoptosis. Furthermore, E-cadherin knockdown in Merlin-negative MM cells significantly sensitized cells to VS-4718 and induced apoptotic cell death upon VS-4718 treatment. Together, our results suggest that E-cadherin serves as a predictive biomarker for molecular target therapy with FAK inhibitors for patients with mesothelioma and that its expression endows MM cells with resistance to FAK inhibitors.

DOI： 10.1038/onc.2017.147

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担当区分：筆頭著者  

DOI： 10.1007/s11748-015-0525-z