Pleurectomy–decortication (P/D) is lung-sparing surgery with curative intent for malignant pleural mesothelioma (MPM). Visceral pleurectomy is the most challenging step in this procedure. At the beginning of pleurectomy, a sharp pleural incision through the tumor is usually made to create the dissection plane between the visceral pleura and the lung parenchyma, which may cause the spread of tumor cells into the operation field. Here, we describe a sophisticated surgical technique of P/D without any pleural incision (“non-incisional P/D”) to achieve en bloc removal of the entire pleura and tumor, which may improve postoperative survival by preventing tumor spread.

We herein report the case of a 62-year-old man who underwent extrapleural pneumonectomy (EPP) for pleural epithelial hemangioendothelioma (EHE) diagnosed by a pleural biopsy. Pre-operative computed tomography revealed diffuse pleural thickening and pleural effusion in the right thoracic cavity, although metastasis to neither the lymph nodes nor distant organs was detected. We decided to perform EPP based on surgical findings that the tumor had invaded the lung parenchyma. A pathological examination revealed tumor invasion of the lung parenchyma, blood vessel, pericardium, diaphragm and bronchial wall. Despite aggressive treatment, tumor recurrence was detected about 1 month after surgery. Although we controlled the tumor progression using pazopanib, the patient ultimately died 3.5 months after the operation. Pleural EHE is a very rare disease that has a poor prognosis due to its high malignant potential. It is important to formulate strategies matched to individual cases based on disease progression and invasiveness of treatment.

Background: Various anaplastic lymphoma kinase-tyrosine kinase inhibitors (ALK-TKIs) have been approved for use with patients with ALK-positive non–small cell lung cancer (NSCLC). However, little is known about the use of ALK-TKI in real-world clinical settings. Herein we present data from ALK-positive patients with NSCLC at our single institution. Methods: We retrospectively examined data from all patients who were administered ALK-TKIs for NSCLC from March 2012 until October 2018 at our institution. Results: Eleven patients received ALK-TKIs for NSCLC. The median age was 65 years (range, 45–85 years, mean 64 years), and all patients were diagnosed with adenocarcinoma. One patient had no treatment history, and the remaining 10 patients underwent surgery upon initiation of ALK-TKIs. Initial ALK-TKIs included crizotinib (n=2) and alectinib (n=9). The median follow-up was 21 months (range, 3.5–57 months). The 4-year overall survival (OS) rate was 71.4% for all patients. All patients achieved partial response or complete response. Two patients on crizotinib and one patient on alectinib experienced adverse events. Three patients received three types of ALK-TKIs; eight patients received only one ALK-TKI. One patient developed interstitial lung disease (ILD) and underwent salvage surgery after treatment with alectinib. ALK-TKIs affected brain metastases (BM) in four of five patients. Conclusions: Alectinib was associated with the best outcomes of available ALK-TKI medications. Alectinib is a key and approved drug. Alectinib should be administered as a first-line therapy for many patients.

Background Post-esophagectomy bronchopleural fistulas can be life-threatening in patients who are exhausted, for example, by surgical stress and pleural infection; therefore, establishment of a reliable surgical procedure is extremely important. We here report a novel procedure entailing muscle flap closure for bronchopleural fistula. Case presentation A 64-year-old man developed a right bronchopleural fistula after esophagectomy. Because he was exhausted by surgical stress and malnourished, we considered reliable surgical closure of the fistula essential. Intraoperatively, it was found to connect with the membranous portion of the right main bronchus. We decided to close the fistula with a pedicled fourth and fifth intercostal muscle flap. After separating the intercostal muscles near the angle of the rib, we passed a muscle flap between the azygos vein and bronchus and sutured it securely to the fistula. The postoperative course was uneventful, and there was no thoracic infection. Postoperative bronchoscopy confirmed the muscle flap had securely closed the fistula. Conclusions The route and suturing technique of the intercostal muscle flap to a fistula are important, especially in exhausted patients.

BackgroundAlthough immune checkpoint inhibitors (ICIs) for non-small cell lung cancer (NSCLC) have been established as one of standard therapy, the prognostic factors of ICIs remain unclear, aside from the programed cell death-ligand 1 (PD-L1) expression of tumor cells. The aim of this study was to determine the prognostic factors of ICIs.MethodsWe analyzed the clinicopathological data of 44 cases of advanced NSCLC targeted with ICIs in our hospital, between February 2016 and February 2018, in order to determine the prognostic factors of ICIs. We also reviewed the literature regarding ICIs.ResultWe retrospectively analyzed the 44 cases (26 nivolumab and 18 pembrolizumab cases). These patients were 38 men and 6 women, comprising 13 cases of adenocarcinoma, 29 squamous cell carcinoma and 2 unclassified types. Seven patients were using first-line therapy and while the others were using second-line therapy or later. Epidermal growth factor receptor (EGFR) mutation and anaplastic lymphoma kinase (ALK) mutations were negative in all the cases. The response rate and disease control rate were 20.5% and 51.3%, respectively. The median progression-free survival time and median survival time were 146 days and 257 days, respectively. We observed five severe adverse effects (AEs) (three cases of interstitial pneumonia, one of liver dysfunction and one of adrenal failure), that were resolved by steroid pulse therapy. In multivariate analyses, the Eastern Cooperative Oncology Group performance status (ECOG PS), pathological type, standardized uptake value (SUV) on positron emission tomography (PET), white blood cell (WBC) count, neutrophil, neutrophil-to-lymphocyte ratio (NLR), lactate dehydrogenase (LDH) and albumin were independently prognostic factors. There were no significant differences in the prognosis between nivolumab and pembrolizumab.ConclusionsICIs were effective in 44 treated NSCLC cases. Our analysis suggests that while ICIs are effective in treating patients, candidates must be carefully selected and cautiously observed.

We report the case of a 56-year-old woman who underwent pleural biopsy to identify the cause of the right pleural effusion. The pathological diagnosis was epithelial malignant pleural mesothelioma. The patient worked as a junior high school teacher and strongly hoped for continuing work. Thus, we performed pleurectomy/decortication (P/D) as a curative surgery. The operative findings showed pleural thickening that in the lower lobe of the lung. Thus, peeling of the lower lobe was performed. Pleural biopsy was only performed on the upper and middle lobes. As a result, the operation was limited P/D. The pathological findings showed a small number of mesothelioma cells in the upper and middle lobes. The patient received four courses of cisplatin plus pemetrexed systemic chemotherapy after surgery. Continuous maintenance chemotherapy using pemetrexed has been performed until the time of writing. At present, she has continued her work for 6 years after the operation and has extended her retirement age without recurrence.

Complete resection is the mainstay of treatment for thymoma. Even for advanced-stage thymoma with pleural dissemination, complete resection with extrapleural pneumonectomy may provide a favorable prognosis. Pleurectomy decortication, a lung-sparing surgery, has been preferably employed in recent years as an alternative surgical procedure for malignant pleural mesothelioma. However, little has been reported about pleurectomy decortication for other malignant tumors with pleural dissemination. Here, we present the first case of thymoma with pleural dissemination for which complete en bloc resection was achieved with extended pleurectomy decortication.

Background: Several treatment strategies are available for primary spontaneous pneumothorax (PSP). Surgical procedures are also performed in patients with PSP without an absolute indication for surgery. This study was performed to investigate the best treatment strategy for PSP by comparison of the recurrence rate. Materials and methods: From January 2006 to December 2013, 149 patients with PSP aged <= 50 years were treated in our institution. We reviewed the recurrence rate of PSP for each treatment strategy and evaluated the association between the recurrence rate of PSP with the clinicopathological characteristics. We also compared the surgery and non-surgery groups. Results: A significant difference in the PSP recurrence rate was found between the surgery and non-surgery groups (22% vs. 52%, respectively; p < 0.001), patients aged >= 22 and < 22 years (16% vs. 44%, respectively; p < 0.001), and smokers and nonsmokers (13% vs. 43%, respectively; p < 0.001). There were also significant differences in the multivariate analysis (p < 0.001, p = 0.050, and p = 0.001, respectively). In the surgery group, the PSP recurrence rate was significantly different between patients aged >= 22 and < 22 years (7% vs. 38%, respectively; p < 0.001) and smokers and nonsmokers (5% vs. 33%, respectively; p = 0.002). No significant differences were found in the non-surgery group. Conclusions: In the surgical treatment of PSP, it is desirable that smokers stop using tobacco and that patients are >= 22 years old. Moreover, when surgery is being considered, the best timing seems to be when air leakage is present because the air leakage sites can be resected.

This report describes the case of a 67-year-old male with inflammatory breast cancer. He had noticed a left breast mass about seven years previously, but he had ignored it. He then visited our hospital 4 months previously when multiple small masses occurred in the left front chest wall. The tumor was diagnosed as skin metastasis of breast cancer by skin biopsy and he was referred to our department. The tumor cells were positive for estrogen receptor and progesterone receptor, and negative for HER2/neu, and the Ki67 expression was 10-15%. The subtype of his breast cancer was luminal A type. It had secondary inflammatory breast cancer and preceded chemotherapy. Also, as the veins in the lower extremity were filled with thrombus, we gave him an anticoagulant (Edoxaban), but due to the malignant hyper coagulable state (Trousseau syndrome) a CV port could not be implanted. 3 courses of docetaxel every 3 weeks failed to control the disease. Since an obstruction of the right iliac artery was newly observed, the anticoagulant was changed to cilostazol and rivaroxaban, but left second finger and fourth finger necrosis occurred due to peripheral circulatory failure. The condition of the disease was stabilized by FEC (5-FU, epirubicin, cyclophosphamide) therapy, but it became difficult to secure the blood vessel. Without constructing a CV port because of the thrombus, chemotherapy was changed to S-1 oral administration, and strength to the chest wall Modulated radiotherapy intensity modulated radiation therapy (IMRT) was performed. Although the tumor was reduced, the condition of the whole body gradually weakened and the patient died a year and a half after the start of the treatment. This case of inflammatory luminal in male breast cancer that caused thrombus was difficult to treat. Thrombosis in advanced cancer patients is often pointed out, but since male breast cancer patients tend to take a long time to visit the hospital after becoming aware of the mass and arrive at an advanced state, it is necessary to notify the public of the existence of male breast cancer.

Detection of rare tumor cells circulating in the blood (CTCs) presents technical challenges. CellSearch, the only approved system for clinical use, fails to capture epithelial cell adhesion molecule-negative CTCs such as malignant pleural mesothelioma (MPM). We have developed a novel microfluidic device (CTC-chip) in which any Ab to capture CTCs is conjugated. The CTC-chip was coated with an Ab against podoplanin that is abundantly expressed on MPM. Circulating tumor cell-detection performance was evaluated in experimental models in which MPM cells were spiked in blood sampled from a healthy volunteer and in clinical samples drawn from MPM patients. The CTC-chip showed superior CTC-detection performance over CellSearch in experimental models (sensitivity, 63.3%-64.5% vs 0%-1.1%; P < .001) and in clinical samples (CTC-positivity, 68.8% vs 6.3%; P < .001). A receiver operating characteristic (ROC) analysis showed that the CTC test provided a significant diagnostic performance in discrimination of unresectable disease from resectable disease (area under the ROC curve, 0.851; P = .003). The higher CTC count (≥2 cells/mL) was significantly associated with a poor prognosis (P = .030). The novel CTC-chip enabled sensitive detection of CTCs, which provided significant diagnostic and prognostic information in MPM.

Background: Recent retrospective studies have shown that salvage surgery can improve survival with acceptable adverse events, and this procedure has been adapted for lung cancer. However, there are no reports demonstrating the efficacy of salvage surgery combined with aortic resection. Case presentation: A 73-year-old man had received definitive concurrent chemoradiotherapy (carboplatin/paclitaxel, 70Gy) for lung cancer originated from the left upper lobe and infiltrating the thoracic aorta (cT4N1M0 stage IIIA). Although the tumor has shrunk significantly (ycT4N0M0 stage IIIA), radiation pneumonitis occurred. Due to the steroid therapy, radiation pneumonitis was relieved; however, re-enlargement of the primary tumor was observed during steroid tapering. Nonetheless, the lymphatic and distant metastases were controlled. Moreover, aortic invasion was localized to the periphery of the third branch, and the tumor was considered to be resectable. Intraoperatively, we observed macroscopic evidence of aortic invasion in the periphery of the third branch; thus, left upper lobectomy combined with descending aorta resection was performed under partial extracorporeal circulation. The patient is currently active without any recurrence 21months post-surgery. Conclusions: No clear consensus exists regarding salvage surgery combined with aortic resection for primary lung cancer. However, we believe that this surgery may improve the survival of carefully selected patients.

BACKGROUND:Fenestration is performed in patients with bronchopleural fistula to avoid a life-threatening situation. However, usually, this procedure is required 9-cm mean length of the incision with rib resection.CASE PRESENTATION:A 73-year-old man underwent right lower lobectomy with lymph node dissection (ND2a-2) for primary lung cancer (cT1cN2M0 Stage IIIA) with combined pulmonary fibrosis and emphysema. He developed a bronchopleural fistula on postoperative day 20, and we performed emergency fenestration without rib resection using a Lap-protector. The patient reported minimal pain postoperatively. As the rapid deterioration of the general condition due to the recurrence of the tumor was observed at the time of his 1-year postoperative follow-up, closing of the thoracic cavity was abandoned. However, using this fenestration, the control of infection in the thoracic cavity could be sufficiently performed without complications such as pain and pneumonia, and his routine activities were unaffected postoperatively.CONCLUSION:Compared with conventional method, fenestration without rib resection using a Lap-protector is a more convenient and painless technique for postoperative bronchopleural fistula.

The prognostic impact of tumoral programmed death-ligand 1 (PD-L1) expression in correlation with neutrophil-to-lymphocyte ratio (NLR) was retrospectively assessed in 83 patients with completely resected stage I squamous cell carcinoma of the lung, as PD-L1 is a potent regulator of cancer immunity and NLR is a potential surrogate of immune status. Forty-three patients (51.8%) had tumor with positive PD-L1 expression. There was no significant correlation between PD-L1 expression and NLR. PD-L1-positivity failed to provide a significant prognostic impact (overall survival [OS] rate at 5 years, 53.0% in PD-L1-positive patients versus 70.1% in PD-L1-negative patients; P = 0.117). Among NLR-low (<2.2) patients, however, PD-L1-positivity was significantly correlated with a poor prognosis (OS rate at 5 years, 46.1% versus 86.0%; P = 0.020). In contrast, among NLR-high (≥2.2) patients, PD-L1-positivity provided no prognostic impact ( P = 0.680). When NLR status and tumoral PD-L1 status were combined, “NLR-low and PD-L1-negative” was a significant and independent factor to predict a favorable recurrence-free survival (hazard ratio, 0.237 [95% confidence interval, 0.083 to 0.674]; P = 0.007) and OS (hazard ratio, 0.260 [0.091 to 0.745]; P = 0.012). These results suggest the prognostic impact of tumoral PD-L1 expression might be influenced by the status of NLR.

Background and Objectives Pulmonary pleomorphic carcinoma (PPC) is a rare and aggressive subtype of lung cancer. Programmed cell death‐ligand 1 (PD‐L1) expression may be induced in a variety of malignant tumors, but its prognostic implication in PPC remains unclear. Methods Twenty‐six patients with surgically resected PPC were retrospectively reviewed. Immuno‐histochemical staining was used to detect PD‐L1 expression, and PD‐L1 status was classified into “high” or “low” according to the percentage of tumor cells (TCs) expressing PD‐L1 (tumor proportion score, TPS). Results PD‐L1 expression was positive in 20 (76.9%) patients at the cut‐off TPS value of 1%. A receiver‐operating characteristic (ROC) analysis showed that the optimal cut‐off value was 15% for prediction of cancer‐specific death with the area under ROC curve of 0.701 ( P = 0.107). High PD‐L1 expression was associated with a favorable overall survival (100% vs 45.9% at 5 years; P = 0.046) as well as a favorable cancer‐specific survival (88.9% vs 37.5% at 5 years; P = 0.012). A multivariate analysis indicated a trend toward a favorable prognosis associated with high PD‐L1 expression (hazard ratio [HR], 0.254 [95% confidence interval, 0.054‐1.200]; P = 0.084). Conclusions PD‐L1 expression was positive in most PPC cases, and high PD‐L1 expression may predict a favorable prognosis in resected PPC.

BACKGROUND:Thymic carcinoma is uncommon, presents locally at an advanced stage, and behaves aggressively. The optimum treatment for advanced thymic carcinoma is controversial. We retrospectively reviewed our institutional experience with patients with thymic carcinoma.METHODS:We analyzed the clinical data of six patients who underwent total thymectomy for thymic carcinoma at our institution from 2006 to 2016. Variables analyzed included sex, age, histological classification, Masaoka staging, postoperative treatment, and recurrence.RESULTS:The clinical characteristics of the six patients with thymic carcinoma (median age, 56 years; five men and one woman) were as follows: squamous cell carcinoma (n=5); sarcomatoid carcinoma (n=1); Masaoka stages II (n=1), III (n=2), IVa (n=1), and IVb (n=2). Four patients underwent combined pulmonary resection (66.7%) as a component of en bloc resection due to suspicion of pulmonary invasion. Four patients (66.7%) received postoperative therapy, and complete resection was achieved for four patients. There were no perioperative deaths. One patient experienced a recurrence.CONCLUSIONS:Complete resection for thymic cancer improved the prognosis of our patients, indicating that robust studies will be required to confirm our findings.

PD-L1 is one of the important immune checkpoint molecules that can be targeted by cancer immunotherapies. PD-L1 has a soluble form (sPD-L1) and a membrane-bound form (mPD-L1). Conventional enzyme-linked immunosorbent assay (ELISA) systems can detect sPD-L1 using anti-PD-L1 capture antibody through the antigen-antibody reaction, but cannot evaluate the quality and function of sPD-L1. In this study, we developed a novel ELISA system for the detection and quantification of sPD-L1 with PD-1-binding capacity (bsPD-L1). To capture bsPD-L1 through the ligand-receptor reaction, the anti-PD-L1 capture antibody in the conventional ELISA was replaced with PD-1-Ig fusion protein in the new ELISA. The new ELISA could detect bsPD-L1 in 29 out of 75 plasma samples from patients with non-small cell lung cancer (NSCLC), with higher sensitivity and frequency than the conventional ELISA. The western blot analysis showed that sPD-L1 in the plasma was glycosylated. Treatment of the samples with glycosidase reduced the absorbance determined by the new ELISA but had no effect on the absorbance determined by the conventional ELISA. These results suggest that glycosylation of sPD-L1 is important for its binding to the immobilized PD-1 in the new ELISA. Our new ELISA system may be useful for the evaluation of functional sPD-L1 with PD-1-binding capacity in cancer patients.