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Advances in drug therapy and radiotherapy for non-small cell lung cancer resulted in an increased number of salvage surgeries for initially unresectable tumors. This study aimed to evaluate the safety and efficacy of salvage surgery for non-small cell lung cancer.We defined salvage surgery as (1) surgery for local recurrence/residual tumor after definitive chemoradiotherapy/radiotherapy (salvage surgery in a narrow sense) or (2) conversion surgery after non-surgical treatment. We retrospectively analyzed patients who underwent salvage surgery at four Keio University-affiliated hospitals.Forty-six patients were included. The initial clinical stage was I in 4 patients (9%), III in 19 (41%), and IV in 23 (48%). Initial treatment before salvage surgery was chemoradiotherapy in 10 patients (24%), radiotherapy in 4 (9%), and drug therapy in 32 (67%). Pneumonectomy, lobectomy, segmentectomy, and wedge resection were performed in 2 (4%), 37 (80%), 3 (7%), and 4 (9%) patients, respectively. Complete resection was achieved in 41 patients (89%). Postoperative complications occurred in 11 patients (24%). Initial chemoradiotherapy/radiotherapy was an independent predictor of postoperative complications (odds ratio 10, p = 0.03). The 30- and 90-day mortality rates were 0 and 2%, respectively. The 5-year overall and progression-free survival rates were 66 and 30%, respectively.The safety and efficacy of salvage surgery for non-small cell lung cancer were acceptable. Salvage surgery was a viable treatment option for selected patients with recurrent/residual tumors after non-surgical treatments.

Histologic subtyping offers some prognostic value in lung adenocarcinoma. We thus hypothesized that histologic subtypes may be useful for risk stratification of brain metastasis (BM). In this study, we aimed to investigate the impact of histologic subtypes on the risk for BM in patients with resected lung adenocarcinoma.Of 1099 consecutive patients who had undergone curative-intent surgery (2000-2014), 448 patients who had undergone complete resection for lung adenocarcinoma were included in this study. Correlated clinical variables and BM-free survival were analyzed.Micropapillary predominance was significantly associated with higher risk of BM after complete resection in univariate analyses (P.001). In addition, multivariate analyses showed that micropapillary predominance was an independent risk factor for BM (hazard ratio = 2.727; 95% confidence interval, 1.260-5.900; P = .011), along with younger age and advanced pathologic stage. Unlike the other subtypes, an increase in the percentage of the micropapillary subtype was positively correlated with an increase in BM frequency. Patients with micropapillary adenocarcinoma showed significantly poorer brain metastasis-free survival compared with those with non-micropapillary adenocarcinoma (3 years, 78.2% vs. 95.6%; 5 years, 67.3% vs. 94.3%; P.001).The current study demonstrated a significant correlation between micropapillary subtype and higher risk of BM in patients with resected lung adenocarcinoma. This routine histologic evaluation of resected adenocarcinoma may provide useful information for the clinician when considering postoperative management in patients with lung adenocarcinoma. Histologic subtyping offer some prognostic value in lung adenocarcinoma. Because brain metastasis is critical and often refractory to systemic chemotherapy, early detection is clinically important to achieve effective local treatment. We retrospectively analyzed the association between histologic subtypes and occurrence of brain metastasis and found a significant association between micropapillary predominance and higher risk for brain metastasis. Our findings may be relevant when considering postoperative management.

Programmed death‐ligand 1 (PD‐L1) is an immune modulator that promotes immunosuppression by binding to programmed death‐1 of T‐lymphocytes. Although tumor cell PD‐L1 expression has been shown to be associated with the clinical response to anti–PD‐L1 antibodies, its concise regulatory mechanisms remain elusive. In this study, we evaluated the associations of tumor PD‐L1 expression and immune cell infiltrating patterns in 146 cases of early lung adenocarcinoma (AC) to investigate the possible extrinsic regulation of tumor PD‐L1 by immune cells. Using immunohistochemistry, cell surface PD‐L1 expression in tumor cells was observed in 18.5% of stage 0‐IA lung AC patients. Tumor PD‐L1 positivity was significantly associated with stromal invasion, which was accompanied by increased tumor‐associated macrophages (TAM), CD8+ cytotoxic T cells and FoxP3+ regulatory T cells. Among these immune cells, TAM and CD8+ T cells significantly accumulated in PD‐L1‐positive carcinoma cell areas, which showed a tumor cell nest‐infiltrating pattern. Although CD8+ T cells are known to induce tumor PD‐L1 expression via interferon‐ɣ production, the increased TAM within tumors were also associated with tumor cell PD‐L1 positivity, independently of CD8+ T cell infiltration. Our in vitro experiments revealed that PD‐L1 expression in lung cancer cell lines was significantly upregulated by co–culture with M2‐differentiated macrophages; expression of PD‐L1 was reduced to baseline levels following treatment with a transforming growth factor‐β inhibitor. These results demonstrated that tumor‐infiltrating TAM are extrinsic regulators of tumor PD‐L1 expression, indicating that combination therapy targeting both tumor PD‐L1 and stromal TAM might be a possible strategy for effective treatment of lung cancer., In this study, we showed that tumor‐associated macrophage (TAM) infiltration was an additional factor related to tumor programmed death‐ligand 1 (PD‐L1) expression in early lung adenocarcinoma. Our in vitro experiments demonstrated that M2‐differentiated macrophages facilitated tumor PD‐L1 expression through transforming growth factor‐β. These results suggested that TAM were extrinsic regulators of tumor PD‐L1 expression and could serve as potential therapeutic targets.

Background. A parenchymal surgical margin of“the clinical tumor size or more” or “2.0 cm or more” has been widely recognized as the optimal margin distance to avoid locoregional recurrence after sublobar resection for non-small cell lung cancer (NSCLC) of 2.0 cm or less. However, the safe margin distance to avoid locoregional recurrence for NSCLC larger than 2.0 cm remains unclear. Patients and Methods. Among 1,338 patients with resected primary lung cancers at two institutions between 2007 and 2016, 85 clinical N0M0 patients with NSCLCs larger than 2.0 cm who underwent sublobar resection were extracted. We classified these 85 NSCLCs as ground glass opacity (GGO)-dominant type or solid-dominant type according to computed tomography (CT) findings. Clinicopathological characteristics and the association between locoregional recurrence and margin distance were evaluated. Results. The median clinical tumor size was 2.5 (2.1-4.9) cm. Based on CT findings, 14 tumors (16%) were considered GGO-dominant type and 71 (84%) were solid-dominant type. No lymph node metastasis, lymphatic permeation or vascular invasion was pathologically confirmed in GGO-dominant type. All GGO-dominant tumors were resected with a margin distance the size of the solid part on CT or more, resulting in no local recurrence, whereas, solid-dominant tumors recurred locally even if they were resected with a margin distance of “the clinical tumor size or more”. Conclusions. The optimal surgical margin for NSCLC larger than 2.0 cm was “the size of the solid part on CT or more” for GGO-dominant type, but undefinable for solid-dominant type.

Bronchiolitis obliterans (BO), which begins with lymphocytic bronchiolitis (LB), is the most serious manifestations of chronic rejection following lung transplantation. We have evaluated the effects of intraperitoneal administration of pioglitazone, a peroxisome proliferator-activated receptor (PPAR) gamma agonist, on LB in mice tracheal transplant model. Tracheal grafts from BALB/c or C57BL/6 were transplanted to C57BL/6 recipients. Animals were divided into three groups (n = 8), isograft (IG) and allograft with (AGP) or without (AGN) pioglitazone. Occlusion rate (OR) of transplanted trachea, CD3, FoxP3 positive cell infiltration, and cytokine levels in the transplanted grafts were analyzed at day 7. In the AGP group, OR was significantly lower than in the AGN group (p .01). An average of 305 ± 56, and 317 ± 84 CD3-positive T-cells/section was shown in the AGN and AGP groups, respectively (p = .761). Interestingly, an average of 24 ± 18, and 88 ± 28 FoxP3-positive regulatory T-cells (Tregs)/section was shown in AGN and AGP groups, respectively (p = .001). FoxP3 and IL-4 mRNA expression was significantly higher in the AGP group. Pioglitazone can suppress the luminal occlusions of the tracheal graft in an allograft through enhanced Treg infiltration, and may provide new therapies to prevent BO.

Purpose Bronchiolitis obliterans (BO) and bronchiolitis obliterans syndrome were recognized as serious complications after lung transplantation. We hypothesized that pioglitazone, a peroxisome proliferator-activated receptor (PPAR)-γ agonist, could prevent airway rejection in established mouse orthotopic tracheal transplant models. Methods Tracheal grafts from wild type BALB/c or C57BL/6 were transplanted to C57BL/6 recipients. Experimental groups were treated with multiple doses of pioglitazone, at total 5mg/kg per day. Histopathologic evaluation of luminal obliteration was blindly reviewed at day 7. Immunohistochemistry for CD3, FoxP3 and real-time PCR analyses for cytokines were performed. Results Allografts treated with pioglitazone revealed a striking reduction of thickening in airway layers (P Conclusion Pioglitazone leads to decreased airway graft luminal occlusion and induced accumulation of Tregs in the graft. These data indicated a strong protective role for pioglitazone against BO. The potential mechanism of this beneficial effect of pioglitazone appears to increase the production of IL-4 and decrease the production of IFN-γ, TNF-α and IL-6.

Giant lamellar bodies (GLBs) are intra-alveolar eosinophilic concentric lamellar structures that typically have a diameter of 20–30 μm. GLBs are most commonly associated with sclerosing pneumocytoma, which was formerly known as sclerosing haemangioma.1, 2 In addition, GLBs have frequently been observed in mucosa-associated lymphoid tissue (MALT)-type lymphomas, and Perry et al.3 have suggested that GLBs may favour a diagnosis of lymphoma over follicular bronchiolitis. Other conditions that reportedly contain GLBs include alveolar adenoma,4 plasma cell granuloma,4 pulmonary alveolar proteinosis5, and Mycobacterium avium complex lung disease.6 Thus, GLBs have typically been associated with benign or low-grade lung lesions, and, to the best of our knowledge, there have been no reports regarding GLBs in lung carcinoma. Here, we describe 8 lung adenocarcinomas that harboured GLBs. This article is protected by copyright. All rights reserved.

We have experienced 6 cases with resection and reconstruction of sternum. They were 1 with osteosarcoma, 1 with synovial sarcoma, 1 with sternal metastasis of fallopian tube cancer, 1 with sternal metastasis of thyroid cancer, 1 with desmoid tumor, and 1 with dermatofibrosarcoma protuberance. Resection of both manubrium and sternum was performed in 3 cases and sternum resection in 3. There was no total resection. We used a titanium reconstruction plate and titanium mesh in 3 cases, a titanium reconstruction plate and polypropylene mesh in 2, titanium mesh in 1 for reconstruction of bony defect, and rectus abdominis myocutaneous flap in 3, pectralis major muscle flap in 2, latissimus doris myocutaneous flap in 1 for reconstruction of soft tissue defect. Postoperative courses were uneventful, and flail chest was not observed. Reconstruction of the bony defect of the anterior chest wall with the titanium reconstruction plate and titanium mesh or polypropylene mesh was effective by providing sufficient rigidity as well as protection of the thoracic organs.

We report the case of a 46-year-old Japanese woman with past medical history of right nephrectomy for as sarcomatoid renal cell carcinoma 14 years earlier. A pulmonary nodule was detected in the left upper lobe 7 years after nephrectomy and it had grown slowly for 6 years. We performed wedge resection for the tumor because we suspected that the nodule was metastasis from the renal tumor. But the nodule was diagnosed as epithelioid angiomyolipoma since the nodule was positive for HMB-45 and negative for epithelial markers and S-100 protein by immunohistochemical analysis. Therefore her disease was revised as a solitary pulmonary metastasis from renal epithelioid angiomyolipoma. Epithelioid angiomyolipoma is potential malignant mesenchymal tumor because the tumor recurs or metastasizes, and progresses rapidly on one-third of the cases. This case is the first report that the disease was stable for a long time after late recurrence caused.

Acute rejection after lung transplantation is the main risk factor for the development of bronchiolitis obliterans (BO). Carbon monoxide (CO) can provide anti-inflammatory effects and may serve to limit tissue injury in airway transplant. Here, we tested the ability of carbon monoxide releasing molecule-2 (CORM-2) to prevent airway rejection. Tracheal grafts from BALB/c or C57BL/6 were transplanted to C57BL/6 recipients. Experimental groups were treated with multiple doses of CORM-2. Histopathological evaluation of luminal obliteration was blindly reviewed. Immunohistochemistry and real-time RT-PCR analyses were performed. Allografts treated with CORM-2 revealed a striking reduction of thickening in epithelial and subepithelial airway layers (P < 0.01) at day 7 in orthotopic trachea transplantation model compared with allografts treated with vehicle. In heterotopic trachea transplantation model, CORM-2 treated allografts showed a reduction of luminal obliteration (P < 0.01) at days 14 and 21. There was also a concordant decrease in CD3(+) lymphocytes and macrophages in CORM-2 treated allografts. IFN-γ, IL-2 and IL17A mRNA expressions were reduced dramatically by systemic administration of CORM-2. These data implicate CORM-2-derived CO has an important protective function in experimental BO, and may represent a target for the therapeutic intervention of chronic lung allograft rejection.