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We previously established a novel method of lung repair called the ventilation and anchoring (V/A) method. We evaluated the usefulness of the V/A method for controlling air leakage during pleurectomy/decortication (P/D).For this study, we enrolled patients with malignant pleural mesothelioma (MPM) who planned to receive P/D. Our lung repair method involves (1) suturing lung parenchyma for an apparent injured lesion and (2) coating the lung parenchyma with fibrin glue (FG) using the V/A method. The tidal volume (TV) was measured under pressure-controlled ventilation in the ipsilateral-affected lung 10 times at the following four points: after thoracotomy, at completion of visceral pleurectomy, after suturing lung parenchyma, and 5 min after coating with FG. The primary endpoint was the mean TV (mTV) change, and the secondary endpoints were the duration of air leakage and incidence of pleurodesis.Between April 2014 and April 2016, 25 patients of the 29 consecutive patients enrolled were eligible. The mTV significantly decreased after completion of visceral pleurectomy but significantly increased after repair of the lung parenchyma, especially after coating with FG. The median duration of postoperative air leakage was 4 days (range: 2-19 days). Postoperative air leakage 7 days was observed in 11 (44%) patients. Of these 11 patients, 6 received pleurodesis; however, no further revision was needed.Significant increases in TV were observed after coating with FG via the V/A method during P/D. Coating with FG using the V/A method can contribute to a reduction in air leakage during P/D.

Background Evaluation of tumor markers may facilitate follow-up of malignant pleural mesothelioma (MPM). We aimed was to evaluate the value of tumor markers for monitoring and predicting recurrence in patients with MPM. Methods In total, 152 patients who underwent curative-intent surgery after induction chemotherapy for MPM between July 2004 and December 2017 were retrospectively reviewed. Preoperative and postoperative (≤3 months after surgery) levels of soluble mesothelin-related peptide (SMRP), cytokeratin 19 fragment (Cyfra21-1), and tissue polypeptide antigen (TPA) and rates of recurrence and non-recurrence were evaluated. Factors associated with recurrence-free survival (RFS) were assessed using the Kaplan-Meier method and Cox proportional hazards model. Results Of the 152 patients, the positive rates of preoperative SMRP, Cyfra21-1, and TPA, levels were 26.7%, 8.6%, 9.6%, respectively; the respective postoperative levels were 4.0%, 6.3%, and 6.5%; the respective levels in patients with recurrence were 39.3%, 31.4%, 28.6%; the respective levels in patients with no recurrence were 3.7%, 0.0%, 3.8%. Nearly half (45.2%) of the patients with recurrence exhibited an increase in one or more tumor marker levels. Multivariate analysis revealed that the preoperative positive rates of one or more of the three tumor markers (hazard ratio: 1.8, 95% confidence interval: 1.1-2.8; P=0.02) were independent significant predictors of recurrence. Conclusions The positive rates of SMRP, Cyfra21-1, and TPA in recurrence-free patients were extremely low, with high specificity. Preoperative levels of SMRP, Cyfra21-1, and TPA, which identified patients with a high risk for recurrence, could improve management of patients with MPM.

A few studies have reported the incidence and clinical implications of complications after pleurectomy/decortication (P/D). The aim of this study was to assess the details of complications and predictive factors of particularly durable air leak with P/D. Data on 163 consecutive patients who underwent neoadjuvant chemotherapy (NAC) followed by P/D for malignant pleural mesothelioma between September 2012 and May 2020 at our institution were retrospectively analyzed. Postoperative complications and the significance of various preoperative risk factors for air leak > 10 days (AL10) to identify the group having a higher risk for particularly durable air leak were investigated. Risk factors for AL10 were sought using univariate and multivariate analyses. Of 163 patients, 30- and 90-day mortality was 0.6% and 2.5%, respectively. Eighty-four (51.4%) patients experienced grade III or worse postoperative complications according to the Clavien–Dindo classification. The median duration of air leak was 7 postoperative days. AL10 occurred in 53 (32.5%) patients. Fifty-eight patients (35.6%) underwent pleurodesis and five patients (3.1%) underwent reoperation to control the air leak. On univariate analysis, performance status (PS; p = 0.003), prognostic nutritional index (p = 0.01), and pleural effusion (p = 0.04) were statistically significant risk factors for AL10, while on multivariate analysis, PS (odds ratio 4.0, 95% confidence interval 1.3–12.7; p = 0.02) remained the only variable predicted for AL10. Recent postoperative mortality rates in NAC followed by P/D are quite acceptable. Approximately one in every three patients experienced AL10, and PS may be a risk factor associated with AL10.

IntroductionThoracoscopic surgery is performed for refractory or recurrent primary spontaneous pneumothorax (PSP). To reduce postoperative recurrence, additional treatment is occasionally adopted during surgery after bulla resection. However, the most effective method has not been fully elucidated. Furthermore, the preference for additional treatment varies among countries, and its efficacy in preventing recurrence must be evaluated based on settings tailored for the conditions of a specific country. The number of registries collecting detailed data about PSP surgery is limited. Therefore, to address this issue, a prospective multicentre observational study was performed.Methods and analysisThis multicentre, prospective, observational study will enrol 450 participants aged between 16 and 40 years who initially underwent PSP surgery. Data about demographic characteristics, disease and family history, surgical details, and CT scan findings will be collected. Follow-up must be conducted until 3 years after surgery or in the event of recurrence, whichever came first. Patients without recurrence will undergo annual follow-up until 3 years after surgery. The primary outcome is the rate of recurrence within 2 years after surgery. A multivariate analysis will be performed to compare the efficacy of different surgical options. Then, adverse outcomes correlated with various treatments and the feasibility of treatment methods will be compared.Ethics and disseminationThis study was approved by the local ethics committee of all participating centres. The findings will be available in 2025, and they can be used as a basis for clinical decision-making regarding appropriate options for the initial PSP surgery.Trial registration numberNCT04758143.

Treatment options for bronchial fistula (BF) after pneumonectomy are often limited and carry significant morbidity and mortality. The patient underwent right extrapleural pneumonectomy for malignant pleural mesothelioma had BF without macroscopic fistula found by bronchography. We treated this minor BF using bronchoscopy with the administration of OK-432, fibroblast growth factor basic, and fibrin glue sealant. Two weeks after this treatment, we confirmed the improvement of the fistula by bronchography. Bronchoscopic therapy for BF was useful for a small, early fistula without infection.

We compared less invasive surgery with conventional surgery for malignant pleural mesothelioma (MPM). We retrospectively reviewed consecutive patients with MPM who received surgery at Hyogo College of Medicine between July 2004 and April 2016. Patients underwent multimodal treatment comprising chemotherapy (neoadjuvant and/or adjuvant) and surgery with or without 54 Gy hemithoracic radiotherapy. Patients were grouped into 3 groups according to the surgery intended: Conventional extrapleural pneumonectomy was intended in Group 1 (until August 2009); less invasive extrapleural pneumonectomy was intended in Group 2 (after September 2009); pleurectomy/decortication was intended in Group 3 (after September 2012). We included 152 patients (median age 64 [37-71] years; 131 men, 21 women), mostly with epithelioid subtypes (91.4%). Of them, 149 (98.0%) underwent neoadjuvant chemotherapy and 117 (77.0%) underwent surgery (60 had extrapleural pneumonectomy and 57 had pleurectomy/decortication). Macroscopic complete resection was achieved in 94.9% (111/117), and the mortality rates at 30 and 90 days were 1.7% (2/117) and 3.4% (4/117), respectively. The overall median survival time and progression-free survival for all 152 patients were 34.9 and 17.4 months. The overall median survival time for Groups 1, 2, and 3 were 18.5, 41.9, and 43.4 months, respectively. The progression-free survival for Groups 1, 2, and 3 were 12.0, 24.5, and 21.8 months, respectively. Compared with conventional surgical techniques, less invasive surgery for MPM yielded lower surgical risks and comparable or improved survival.

A few studies have reported the incidence and clinical implications of complications after pleurectomy/decortication (P/D).The aim of this study was to assess the details of complications and predictive factors of particularly durable air leak with P/D.Data on 163 consecutive patients who underwent neoadjuvant chemotherapy (NAC) followed by P/D for malignant pleural mesothelioma between September 2012 and May 2020 at our institution were retrospectively analyzed. Postoperative complications and the significance of various preoperative risk factors for air leak 10 days (AL10) to identify the group having a higher risk for particularly durable air leak were investigated. Risk factors for AL10 were sought using univariate and multivariate analyses.Of 163 patients, 30- and 90-day mortality was 0.6% and 2.5%, respectively. Eighty-four (51.4%) patients experienced grade III or worse postoperative complications according to the Clavien-Dindo classification. The median duration of air leak was 7 postoperative days. AL10 occurred in 53 (32.5%) patients. Fifty-eight patients (35.6%) underwent pleurodesis and five patients (3.1%) underwent reoperation to control the air leak. On univariate analysis, performance status (PS; p = 0.003), prognostic nutritional index (p = 0.01), and pleural effusion (p = 0.04) were statistically significant risk factors for AL10, while on multivariate analysis, PS (odds ratio 4.0, 95% confidence interval 1.3-12.7; p = 0.02) remained the only variable predicted for AL10.Recent postoperative mortality rates in NAC followed by P/D are quite acceptable. Approximately one in every three patients experienced AL10, and PS may be a risk factor associated with AL10.

An 85-year-old woman was found to have a nodule in the left S6 of the lung on computed tomography (CT); the pathological diagnosis from the CT-guided biopsy was adenoid cystic carcinoma. We accordingly performed left lower lobectomy. Pathologically, the biphasic cell population showed admixtures in varying proportions of epithelial and stromal elements, thereby indicating pleomorphic adenoma (PA). PA of the lung is extremely rare with reports of only 20 patients so far. Interestingly, this case was difficult to diagnose using CT-guided biopsy because the overview and biphasic cell population obtained on biopsy were garbled. Here we have reported our rare experience of PA.

The change in TNM classification of malignant pleural mesothelioma (MPM) between the seventh and eighth edition classifications has resulted in the downstaging of many advanced-stage patients into pathological stage IB. Many mesotheliomas without lymph node metastasis have been classified as stage IB in the eighth edition classification. Stage IB mesotheliomas comprised a heterogeneous group with different prognosis. It is necessary to clarify the prognostic factors in this group. Between September 2009 and August 2016, a total of 89 patients with MPM underwent curative intent surgery [pleurectomy decortication n = 57 (64.1%), extrapleural pneumonectomy n = 32 (35.9%)] at our institution. Of these, 40 were reclassified as stage IB according to the eighth edition TNM classification. Independent unfavorable prognostic factors were identified by univariate analyses using the log-rank test and Cox proportional hazards regression models. Three independent significant factors were identified that indicated an unfavorable prognosis: a nonepithelioid subtype, lymphovascular invasion, and preoperative forced expiratory volume in 1 s (FEV1)

Background: In non-small cell lung cancer (NSCLC), circulating tumor cells (CTC) are shed and circulate to the peripheral blood through the pulmonary vein. Previously, CTC count in pulmonary venous blood (pvCTC) was shown to significantly increase after surgical manipulation. Therefore, we assessed the correlation between the changes in the pvCTC count (ΔpvCTC) and clinical outcomes. Methods: Consecutive patients with peripheral-type, NSCLC, who underwent lobectomy or bi-lobectomy through open thoracotomy, were enrolled prospectively. Before and after lobectomy, 2.5 mL of blood was drawn from the associated lobar pulmonary vein (PV), and was served for the quantitative evaluation of CTC using the CellSearch ® system. The cut-off point of ΔpvCTC was determined according to clinical outcomes and ΔpvCTC using receiver operation characteristic (ROC) curve. Then the correlation between ΔpvCTC and clinical outcomes was evaluated by Kaplan-Meier analyses and log-rank test. In addition, the correlation between ΔpvCTC and perioperative variables was assessed. Results: A total of 30 patients were enrolled, tumor recurrence occurred in 11 patients over a median follow-up of 64.4 months. Of these, 7 patients had distant metastasis and 4 had local recurrence. The median ΔpvCTC was 49 cells/2.5 mL, and pvCTC-count was increased during surgical manipulation in 24 patients (80%). We divided patients into two groups based on ΔpvCTC with the cut-off value as 119 cells/2.5 mL according to ROC curve. Significant shorter time to distant metastasis (TDM) (P=0.0123) was observed in high ΔpvCTC group (ΔpvCTC ≥119 cells/2.5 mL) than low ΔpvCTC group (ΔpvCTC Conclusions: Increasing pvCTC count during surgical manipulation was significantly correlated with postoperative distant metastasis in completely resected NSCLC patients. Significant shorter TDM was observed in patient with high ΔpvCTC group.

Additional chemotherapy is often not feasible in patients with recurrent malignant pleural mesothelioma (MPM) undergoing extrapleural pneumonectomy (EPP), due to deteriorated cardiopulmonary reserve. We thus examined the feasibility and efficacy of additional chemotherapy in patients with recurrent MPM after EPP. A retrospective review was conducted of 59 consecutive patients who underwent bi-/tri-modal treatment with induction chemotherapy, EPP, and radiation therapy from July 2004 to August 2013 at Hyogo College of Medicine (Nishinomiya, Japan). Of 59 patients, 39 (male/female = 31/8, right/left = 15/24, pathological stage I/II/III/IV = 1/7/23/3, bi-/tri-modality = 27/12) relapsed at a median age of 62 (range 37–71) years. The median time to recurrence after EPP was 11.6 months. Of the 39 relapsed patients, 12 received best supportive care alone, six started but discontinued chemotherapy, and the remaining 21 (53%) completed more than three cycles of intravenous chemotherapy. The median survival time after EPP was significantly longer in 21 patients who received additional chemotherapy than in 18 patients who did not (39.2 vs. 12.2 months, P = 0.009). Additional systemic chemotherapy was successfully administered in more than 50% of relapsed patients after bi-/tri-modal treatment, which included EPP, and resulted in a longer survival in comparison with best supportive care alone.

Tumor resection with cardiopulmonary bypass (CPB) remains controversial in the field of oncology. Here, we present a 57-year-old male patient with locally advanced squamous cell carcinoma. The tumor was located in the left hilum and invaded the left atrium. Complete resection, left pneumonectomy combined with partial left atrium resection, was achieved using CPB. We evaluated the circulating tumor cell (CTC) counts, as a surrogate for micrometastasis, in peripheral blood and the CPB circuit. Both CTC counts were 0, which could indicate local disease without micrometastasis. CTC count may be a useful indicator for tumor resection with CPB in lung cancer.

A 55-year-old man with malignant pleural mesothelioma underwent multimodality treatment comprising induction chemotherapy followed by extrapleural pneumonectomy and radiation therapy. After 2.5 years, focal recurrence occurred, with computed tomography revealing a tumor in the left cardiophrenic angle. Surgery was considered a problem for the patient because of the previous extrapleural pneumonectomy and difficult tumor location. Radiofrequency ablation was therefore performed; the course was uneventful, and there was no recurrence. Radiofrequency ablation should be considered an option to treat recurrence of malignant pleural mesothelioma.

Background/aim We performed multimodality therapy comprising preoperative chemotherapy, extrapleural pneumonectomy (EPP), and radiation therapy for patients with malignant pleural mesothelioma (MPM). Although multimodality therapy resulted in good prognosis, further improvement is required. Therefore, herein, we analysed the prognostic factors using surgical specimens and searched for suitable molecular targets to improve the prognosis after multidisciplinary treatment. Patients and methods Forty-six patients with MPM underwent multimodality therapy. Paraffin-embedded surgical samples were used for immunohistochemistry to evaluate the expression of phosphorylated (p-) AKT, extracellular signal-regulated kinase (ERK), mammalian target of rapamycin (mTOR), mitogen-activated protein kinase (MAPK), eukaryotic translation initiation factor 4E-binding protein 1 (4E-BP1), and S6 ribosomal protein (S6RP). Results On univariate and multivariate analyses, significant differences were observed according to the histological type, pathological stage, and p-mTOR expression rate. Conclusion The prognosis of MPM is affected by p-mTOR expression, suggesting that molecular-targeted treatment might be used during multimodal therapy for MPM.

Background Most patients with malignant pleural mesothelioma experience recurrence after treatment. However no clinical studies have evaluated postrecurrence survival after pleurectomy/decortication for malignant pleural mesothelioma. This study aimed to clarify postrecurrence survival, treatment, prognostic factors, and recurrence pattern after pleurectomy/decortication. Methods We conducted a retrospective cohort study of 90 patients who underwent neoadjuvant chemotherapy followed by pleurectomy/decortication at our hospital between September 2012 and December 2017. Survival and recurrence were calculated using the Kaplan-Meier method with the log-rank test. Clinical factors related to postrecurrence survival were assessed using multivariate analysis with the Cox proportional hazards model. Results Of 90 patients, 57 (63.3%) developed recurrence. The 1- and 3-year recurrence-free survival rates were 69.7% and 34.0%, respectively (median recurrence-free survival time, 19.0 months). With regard to initial recurrence, 39 patients (68.4%) developed local recurrence, 6 (10.5%) developed distant recurrence, and 12 (21.1%) developed both local and distant recurrences. The 1-year postrecurrence survival rate was 59.5% (median post-recurrence survival time, 14.4 months). Forty-three patients (75.4%) underwent a postrecurrence treatment. Multivariate analysis revealed that postrecurrence treatment (hazard ratio, 0.2; 95% confidence interval, 0.07-0.55; P = .002), performance status 0 to 1 (hazard ratio, 0.24; 95% confidence interval, 0.08-0.76; P = .01), and disease-free interval more than 12 months (hazard ratio, 0.4; 95% confidence interval, 0.16-0.99; P = .04) were the independent, favorable, and significant prognostic factors of postrecurrence survival. Conclusions Postrecurrence survival after pleurectomy/decortication is acceptable, and postrecurrence treatment, performance status, and disease-free interval are important prognostic factors of postrecurrence survival.

Background/Aim: A strategy for improving survival of malignant pleural mesothelioma (MPM) patients is earlier diagnosis paired with earlier stage implementation of therapeutic interventions. This study aimed to determine the clinical signs of early-stage MPM to aid an earlier diagnosis and earlier-stage intervention. Materials and Methods: Out of the 72 cases in our institution, 40 cases with 18F-FDG-PET/CT-negative MPM were retrospectively identified between 2007 and 2015. Overall survival rates were determined and compared with pathological features, histology, and treatment. Results: The biphasic histological type of early-stage MPM was characterized by poor prognosis (p=0.0006). Additionally, the cytology-negative group (Class III and below) showed significantly shorter survival times (p=0.0290). There was no significant difference in survival between patients who received pleurectomy and those who received chemotherapy only (p=0.6991). Bimodal therapy resulted in a longer survival rate than trimodal therapy. Conclusion: In early-stage PET-negative MPM cases, biphasic histology and pleural effusion of Class III and below correlated with a poor prognosis. Surgical treatment using pleurectomy/decortication resulted in higher patient survival outcomes than therapy with extrapleural pneumonectomy.

Objectives Definitive diagnosis of the T-component is sometimes challenging in malignant pleural mesothelioma (MPM). Pleural thickness has been reported to be a prognostic factor for MPM and is a potential T-component. Methods We conducted a historical cohort study of patients who underwent neoadjuvant chemotherapy (NAC) and curative-intent surgery as a multimodal treatment for MPM from January 2007 to June 2016. The maximum measurement of pleural thickness among 3 levels and the sum at each level determined using axial computed tomography imaging before and after NAC were termed as "max" and "sum," respectively. We assessed the association between pleural thickness and the primary and secondary end points of overall survival and recurrence-free survival. Survival was analyzed using the Kaplan–Meier curve, log rank test, and multivariate Cox regression model. Results We enrolled 105 patients. We excluded 1 because of missing data; thus, the sample size was 104. The median follow-up period was 29.1 months with recurrence in 78 patients (70.3%) and death in 67 (60.4%). Max and sum ranged from pre (before NAC) values of 0 to 35 (median, 6.05) and 0 to 97 (median, 12.9) to post (after NAC) values of 0 to 30.8 (median, 4.25) and 0 to 67.0 (median, 9.25), respectively. Post values max and sum were associated with overall survival and recurrence-free survival. Post sum values were associated with recurrence (adjusted hazard ratio, 2.59; 95% confidence interval, 1.42-3.83) and death (adjusted hazard ratio, 2.13; 95% confidence interval, 1.16-4.52), respectively. Conclusions Pleural thickness after NAC was an independent prognostic factor in patients who underwent multimodal treatment.

Background: Circulating tumour cells (CTCs) are a potential surrogate for distant metastasis and are considered a useful clinical prognostic marker for metastatic colorectal cancer (mCRC). This prospective study evaluated the preoperative CTC count as a prognostic factor for pulmonary metastasectomy in mCRC patients. Methods: Seventy-nine mCRC patients who underwent curative-intent pulmonary metastasectomy were included. Preoperatively, 7.5 mL of peripheral blood from each patient was quantitatively evaluated for CTCs with the CellSearch ® system. The clinical significance of CTC count was evaluated according to Kaplan-Meier analyses and log-rank test. Multivariate analyses of the perioperative variables were performed. Results: The distribution of CTC counts were as follows; 0 in 66 patients (83.5%), 1 in eight patients (10.1%), 2 in three patients (3.8%), and 3 and 6 in one patient (1.3%). The patients with multiple CTCs (CTC count ≥2) had significant shorter disease-free survival (DFS) (P=0.005, median DFS; 19.8 vs . 8.6 months) and overall survival (OS) (P=0.035, median DFS; not reached vs . 37.8 months), respectively. Multivariate analysis showed the patients with multiple CTCs had elevated risk of recurrence [hazard ratio (HR), 3.28; 95% confidence interval (CI), 1.24–8.67; P=0.017]. Conclusions: The detected rate of CTCs was quite low in mCRC patients who underwent pulmonary metastasectomy. The patient with multiple CTCs had shorter DFS in this study. The larger prospective clinical study is needed to establish the meaning of CTC in mCRC candidate for pulmonary metastasectomy.

Background: The International Association for the Study of Lung Cancer, in collaboration with members of the International Mesothelioma Interest Group (IMIG), developed a large international database and TNM‑based system to study malignant pleural mesothelioma (MPM). However, this database has some limitations since it was a retrospective study and it was based predominantly on surgical cases. The Japanese Joint Committee of Lung Cancer Registry (JJCLCR) employs a project of prospective registry database of patients in Japan with MPM in order to clarify MPM’s epidemiology, current management practices, and prognosis and also to investigate the potential capabilities to target the best patients for therapy. Methods: Tumor stage is described using the 7th and 8th versions of IMIG staging system. This prospective cohort study has been conducted from April 1, 2017 to March 31, 2019. Discussion: We will analyze the data in this registry to determine the most recent outcomes and trends related to MPM treatment in Japan. The present prospective study is expected to validate the 8th version of IMIG staging system, and to investigate whether tumor thickness is a reliable T‑descriptor. Trial registration: ClinicalTrials.gov Identifier: UMIN 000024664

OBJECTIVES: Circulating tumour cells (CTCs) are tumour cells shed from a primary tumour and circulate in the peripheral blood after passing through the drainage vein. In previous studies, we showed that high numbers of CTCs were detected in the drainage pulmonary venous blood of most patients with resectable primary lung cancer, whereas only low numbers of CTCs were detected in the peripheral blood of some patients. Accordingly, this prospective study was conducted to assess changes in CTCs in the drainage pulmonary vein (PV) during lung cancer surgery. METHODS: A total of 30 consecutive peripheral-type primary lung cancer patients who underwent lobectomy (or right upper and middle bilobectomy) through open thoracotomy were included. For each patient, 2.5 ml of blood was sampled from the lobar PV of the primary tumour site before and after surgical manipulation for lobectomy. The CTCs were evaluated quantitatively with the CellSearch® system. RESULTS: Before surgical manipulation, CTCs were detected in PV blood in the majority of patients (22 of 30, 73.3%), although CTCs were detected in peripheral blood in only two patients (6.7%). The median number of CTCs in the PV (pvCTC-count) before surgical manipulation was 4.0 cells/2.5 ml, and there was no significant correlation between pvPV-count and any clinicopathological characteristic, including tumour size, progression and histological type. After surgical manipulation, at the time of completion of the lobectomy, the pvCTC-count significantly increased (median, 60.0 cells/2.5 ml; P= 0.001). The increase in pvCTC-count was significantly associated with microscopic lymphatic tumour invasion (ly); pvCTC-count significantly increased in ly-positive patients (pvCTC-count before and after surgical manipulation, 4.0 and 90.5 cells/2.5 ml, respectively; P= 0.006), but not in ly-negative patients (3.5 and 7.0 cells/2.5 ml, respectively; P= 0.153). The increase in pvCTC-count was not significantly associated with any other clinicopathological factor or with any surgical procedure, including the sequence of vessel interruption. CONCLUSIONS: We documented a significant increase in CTC count in drainage PV blood after surgical manipulation, especially in tumours with lymphatic invasion. We are awaiting survival data at 5 year follow-up examination, which may provide clinical significance of the pvCTC-count.

8548 Background: Since any surgery for malignant pleural mesothelioma (MPM) are cytoreductive, effective chemotherapy is a prerequisite for surgery. In this context, we give neo-adjuvant chemotherapy (NAC) to all surgical candidates. Methods: Hyogo College of Medicine MPM Surgery Program mandates all surgical candidates to receive NAC, and only patients with stable disease (SD) or better response proceeds to surgery. The program comprised NAC followed by extrapleural pneumonectomy (EPP) and hemithoracic radiation until 2012, and NAC followed by pleurectomy/decortication (P/D) and postoperative chemotherapy thereafter. Eligibility criteria are histologically confirmed non-sarcomatoid MPM, clinically resectable stage (T1-3N0-1M0), performance status 0–1, and no major comorbidity. Results: From December 2006 to December 2018, 225 patients were enrolled. Of 225, 24 patients (10.7%, Group A) did not proceed to surgery because of progressive disease (n=23) or serious adverse events (n=2). Of the remaining 201 patients with partial response (n=38, 16.9%) or stable disease (n=163, 72.4%), 19 refused surgery (Group B), 16 received exploratory thoracotomy (Group C), and 165 completed surgery (Group D, EPP58, P/D107). Surgical mortality rates at 30 and 90 days were 1.1% (n=2) and 2.8% (n=5), and surgical morbidity (≧grade 3) was 26.0% (n=47). Median survival time and survival rates of each group were shown in the table. Briefly, 2-yr survival competed among Group B,C and D, whereas 5-yr survival rapidly dropped in Group B and C. Conclusions: Approximately 90% of MPM patients with surgical intent successfully underwent either of EPP or P/D after effective chemotherapy with acceptable surgical mortality and morbidity. Comparison of patients who refused or accepted surgery suggested that surgery contributed to long-term survival. [Table: see text]

To investigate the diagnostic and prognostic value of circulating tumor cells (CTCs), a potential surrogate of micrometastasis, in malignant pleural mesothelioma (MPM). We prospectively evaluated CTCs in 7.5 mL of peripheral blood sampled from patients with a suspicion of MPM. A semiautomated system was used to capture CTCs with an antibody against the epithelial cell adhesion molecule. Of 136 eligible patients, 32 were finally diagnosed with nonmalignant diseases (NM), and 104 had MPM. CTCs were detected in 32.7 % (34 of 104) of MPM patients but in only 9.4 % (3 of 32) of NM patients (P = 0.011). The CTC count was significantly higher in MPM patients than in NM patients (P = 0.007), and a receiver operating characteristic (ROC) curve analysis showed an insufficient capability of the CTC test in discrimination between MPM and NM, with an area under ROC curve of 0.623 (95 % confidence interval, 0.523–0.723; P = 0.036). Among MPM patients, CTCs were more frequently detected in patients with epithelioid subtype (39.7 %, 31 of 78) than in those with nonepithelioid subtypes (11.5 %, 3 of 26; P = 0.016). Positive CTCs (CTC count ≥1) were a significant factor to predict a poor prognosis among epithelioid patients (median overall survival, 22.3 months for positive CTCs vs. 12.6 months for negative CTCs; P = 0.004) and not in nonepithelioid patients (P = 0.649). A multivariate analysis showed that positive CTCs were a significant and independent factor to predict a poor prognosis (hazard ratio, 2.904; 95 % confidence interval, 1.530–5.511; P = 0.001) for epithelioid MPM patients. CTC was a promising marker in diagnosis and prediction of prognosis in MPM, especially in epithelioid MPM.

Background The prognostic significance of the tumor microenvironment, which is created by both cancer cells and cancer-associated fibroblasts (CAFs), has been increasingly recognized. The purpose of this study was to analyze the prognostic markers of stage I squamous cell carcinoma (SqCC), with special reference to the immunophenotypes of both cancer cells and CAFs. Methods A total of 142 patients with stage I SqCC were included in this study. We examined the expressions of E-cadherin, laminin-5, podoplanin, c-MET, carbonic anhydrase IX (CA-IX), CD10, and CD44 in the cancer cells and those of podoplanin, CA-IX, CD10, and CD44 in the CAFs to evaluate their prognostic value. Results Patients with low E-cadherin expression in the cancer cells showed a significantly poorer prognosis than those with high E-cadherin expression in the cancer cells ( P P P = .013 and P = .0011, respectively). According to subgroup analyses combining E-cadherin expression in cancer cells and podoplanin expression in CAFs, 5-year overall survival of patients with low E-cadherin expression in the cancer cells and high podoplanin expression in the CAFs was 7.0% and showed a significantly poorer prognosis as compared with other groups ( P Conclusions The current study indicates that immunophenotypes of CAFs could have a prognostic value independent of those of the cancer cells in SqCC.

Worldwide studies on lung adenocarcinoma have demonstrated a genetic divergence of the epidermal growth factor receptor (EGFR) pathway according to ethnicity, such as higher frequency of activated EGFR mutations among East Asian patients. However, such information is still lacking in some developing countries.We investigated the frequency of EGFR mutations among Bangladeshi patients with adenocarcinoma of the lung. Fine-needle aspiration tissue samples were collected from 61 Bangladeshi patients. Polymerase chain reaction-single-strand conformation polymorphism was performed on extracted DNA for mutational analysis of EGFR exons 19 and 21.EGFR mutations were found in 14 of 61 (23.0 %) Bangladeshi patients. There was no significant difference in EGFR mutation rate with regard to patient's age, sex, smoking history, clinical stage of lung cancer, subtypes of adenocarcinoma, and tumor differentiation.The present study revealed that the EGFR mutation rate in Bangladeshi patients with adenocarcinoma of the lung was higher than in African-American, Arabian, and white Caucasian patients, and was lower than in East Asia.

Background An atypical type A thymoma variant was newly added to the WHO classification of type A thymoma family in 2015. Case presentation A 72-year-old female was present a large round mass in the anterior mediastinum. The radiological examination led to a preoperative diagnosis of non-invasive thymoma. Tumor resection was undertaken via median sternotomy. Complete removal of the mediastinal tumor was achieved. Pathological examination revealed that the tumor cells were spindle- and oval-shaped with atypia. Immunohistochemical work-up revealed that the tumor was type A thymoma. On the basis of these findings, the tumor was finally diagnosed to be an atypical type A thymoma variant. Conclusions Preoperative diagnosis as atypical type A thymoma variant based on radiological examination is difficult. In case of atypical type A thymoma variant, a careful postoperative systemic follow-up should be done.

Lung adenocarcinomas represent a morphologically heterogeneous tumor composed of an admixture of different histologic subtypes (lepidic, papillary, acinar, and solid subtype). The presence of a solid subtype component is reported to be associated with a poorer prognosis. The aim of this study was to evaluate the characteristic immunophenotype of the solid subtype component compared with the immunophenotypes of other components. We analyzed the clinicopathological characteristics of stage I adenocarcinoma patients with predominant solid subtype disease. Furthermore, we immunostained adenocarcinomas with predominant lepidic, papillary, acinar, and solid subtype components (n = 23 each) for 10 molecular markers of tumor invasiveness and scored the results. Patients showing predominance of the solid subtype component (solid subtype adenocarcinoma) had a poorer prognosis than those showing predominance of the lepidic, papillary, or acinar component. Lymphovascular invasion was more often detected in solid subtype tumors than in others. The solid subtype component showed a significantly stronger staining intensity of laminin-5 expression than the lepidic, papillary, and acinar components (P

In 2016, the Annals of Thoracic Surgery published a retrospective analysis of a single institutional experience of pleurectomy/decortication (P/D) plus intraoperative photodynamic therapy (PDT) in patients with malignant pleural mesothelioma (MPM) (1). Out of a total of 90 patients who underwent P/D, 73 patients with pure epithelioid subtype were analyzed. Although most of the patients had advanced MPM, macroscopic complete resection was achieved in all patients, and the overall median survival time was almost 3 years.

e24326Background: The prognosis of malignant pleural mesothelioma (MPM) is very poor; a new drug for MPM is need. The percentage of p16 loss in MPM patients is high. We hypothesized that CDK4/6 is ...

Well-differentiated papillary mesothelioma (WDPM) is an uncommon tumor with a papillary architecture, bland cytologic features, a tendency toward superficial spread without invasion, and good prognosis with prolonged survival. WDPM occurs primarily in the peritoneum of women, but also rarely in the pleura. We here report a case of 48-year-old woman who developed WDPM in the pleura with no history of asbestos exposure. Tumors were multifocal and widespread with a velvety appearance on the surface of parietal and visceral pleurae resected by extrapleural pneumonectomy (EPP). Tumors showed papillary structures with fibrovascular cores and lined by epithelioid cells. Immunohistochemically, these epithelioid tumor cells were positive for epithelial membrane antigen (EMA), a marker of malignant mesothelioma, with more than 50% positive for p53. Tumor cells microinvaded into subpleural parenchyma of the lung and minimally spread to adipose tissues of the mediastinal lesion. In addition, tumor cells invaded into the chest wall with a trabecular or glandular architecture. Based on these findings, this case is pathologically considered as WDPM of the pleura with malignant potential.

Scimitar症候群は部分肺静脈還流異常症の一亜型であり肺分画症をはじめ種々の合併奇形を併存することが知られている．症例は30歳代女性．背部痛を主訴に近医で胸部CTを行い，右肺から下大静脈へ流入する異常血管と右肺分画症を認め，Scimitar症候群を疑い当科紹介となった．肺動脈造影，大動脈造影を行い右肺から下大静脈へ流入するScimitar veinと下行大動脈から右肺S7に流入する異常血管を認めた．肺体血流比（Qp/Qs）は1.648，シャント率は39％であった．低酸素血症は認めないものの有症状であり，手術適応と判断し右下葉切除，異常血管結紮切離術を行った．切除標本の病理所見では右下葉は全体的に低形成であり気管支の走行異常を認めた．またScimitar veinは通常の肺静脈と異なり壁内の弾性線維の割合が高く中膜のコラーゲン線維が増加していた．

Background Circulating tumor cells in peripheral blood (CTC) is a potential surrogate of distant metastasis, which is the critical factor influencing decision making regarding therapy and prognosis of primary lung cancer patients. After our preliminary study showing that CTCs were detected in peripheral blood in 29.4% of resectable lung cancer patients, we conducted a prospective study on CTC in pulmonary vein (PV) blood because tumor cells apart from the primary tumor may circulate after passing through the drainage PV. Methods A total of 30 consecutive lung cancer patients who underwent thoracotomy were included. The CTCs in peripheral blood and in PV blood from the primary tumor site were quantitatively examined with the CellSearch system, and the numbers of CTCs per 7.5 mL peripheral and PV blood in each patient were represented as periCTC count and pvCTC count, respectively. Results Circulating tumor cell was detected in peripheral blood in 5 patients (16.7%; the periCTC count was 1 in 2 patients; and 2, 3, and 16 in 1 patient each), and the incidence of positive periCTC was higher in squamous carcinoma patients than in adenocarcinoma patients (p = 0.028). Circulating tumor cell was detected in PV blood in most patients (29 of 30, 96.7%), and the mean and median pvCTC counts were 1,195 and 81, respectively (range, 0 to 10,034). There was no significant correlation between pvCTC count and any other patient characteristic, including periCTC count. Conclusions In resectable lung cancer, CTC was positive in peripheral blood of some patients and in PV blood of most patients. A long-term follow-up study to clarify the clinical significance of pvCTC status is warranted.

We present a rare case of perivascular epithelioid cell tumor (PEComa) in the right 6th rib of a 28-year-old man. A plain computed tomography scan showed a round osteolytic lesion in the right 6th rib. The resected tissue contained a globular-shaped, soft tumor. Histologically, the tumor was rich in vasculature and exclusively composed of perivascular epithelioid cells with clear cytoplasm. Immunohistochemically, the tumor expressed diffusely a melanocyte marker, human melanoma black-45, and focally a myogenic marker, alpha-smooth muscle actin, but not an epithelial marker, AE1/AE3. Fontana-Masson-positive melanin pigments were present and c-kit receptor tyrosine kinase (CD117), involved in the development of melanocytes but not myogenic cells, was expressed in tumor cells. These findings indicate that the tumor is PEComa with some differentiation into melanocytes. Notably, owing to the unique location of the occurrence, the tumor occupied bone marrow tissues of the rib, resulting that the tumor has the potential for hematogenous metastasis. In spite of the lack of cells with severe atypia, necrosis, and numerous mitoses, tumor cells invaded into surrounding tissues and overexpressed cyclin D1. To the best of our knowledge, this is the first case report of PEComa arising from the rib with the signs of malignant potential.

Malignant pleural mesothelioma (MPM) is associated with a poor prognosis. The main components of multimodality treatment include surgery, chemotherapy, and radiation therapy. Surgery remains controversial. Two procedures are currently offered: extrapleural pneumonectomy (EPP) and pleurectomy/decortication (P/D). The recent scientific literature suggests that P/D is a well-tolerated procedure, with the potential of becoming a default procedure in multimodality regimens. However, the precise treatment schemes and surgical procedures are yet to be established. In our study, we review the advantages and disadvantages of EPP and P/D, summarize the post-EPP and post-P/D observations (including mortality, morbidity, and median survival time), and discuss the choice of surgical technique (EPP vs. P/D). Moreover, we highlight the aspects of the multimodality treatments that are offered to MPM patients, including chemotherapy, radiotherapy, intensity-modulated radiation therapy, and other types of therapy.

Malignant pleural mesothelioma (MPM) is a rare tumor and associated with very poor prognosis. The median survival time( MST) was 8.9 months for those treated by palliative care only. For a radical treatment, total removal of the tumor is the main therapy as well as other solid tumors, but these diffuse and infiltrate growth pattern of tumor make it difficult. The MST was 13 months for patients treated by surgery only. On the other hand, MST using pemetrexed/cisplatin was 12.1 months. There are negative opinions for invasive surgical treatment such as extrapleural pneumonectomy (EPP). Currently surgical treatment of mesothelioma is conducted as part of the multidisciplinary treatment combined with chemotherapy and radiation therapy.