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Interleukin 32 (IL-32) is a proinflammatory cytokine secreted from several kinds of cancer cells. In the present study, we investigated the significance of IL-32 in lung adenocarcinoma by immunohistochemistry and bioinformatics analysis. IL-32 was positive in cancer cells of 21 cases (9.2%) of total 228 cases. Increased IL-32 gene expression was linked to worse clinical course in TCGA analysis, however, IL-32 expression in immunohistochemistry was not associated to clinical course in our cohort. It was also found that high IL-32 expression was seen in cases with increased lymphocyte infiltration. In vitro studies indicated that IFN-γ induced gene expression of IL-32 and PD1-ligands in lung adenocarcinoma cell lines. IL-32, especially IL-32β, also induced overexpression of PD1-ligands in human monocyte-derived macrophages. Additionally, Cancer-cell-derived IL-32 was elevated by stimulation with anticancer agents. In conclusion, IL-32 potentially induced by inflammatory conditions and anticancer therapy and contribute to immune escape of cancer cells via development the immunosuppressive microenvironment. IL-32 might be a target molecule for anti-cancer therapy. [ABSTRACT FROM AUTHOR]

Immunotherapies that target programmed cell death protein 1 (PD-1) signals are standard therapies for advanced-stage lung cancer, and the expression of programmed death-ligand 1 (PD-L1) in cancer tissue predicts immunotherapy efficacy. Although programmed death-ligand 2 (PD-L2) is expressed in cancer cells and macrophages, similar to PD-L1, its significance in lung cancer is unclear. Double immunohistochemistry analyses using anti-PD-L2 and anti-PU.1 antibodies were carried out on tissue array sections from 231 cases of lung adenocarcinoma, and PD-L2 expression in macrophages was evaluated. High PD-L2 expression in macrophages was associated with longer progression-free survival (PFS) and cancer-specific survival (CSS) and observed more often in females, non-heavy smokers, and patients with epidermal growth factor receptor (EGFR) mutations and those at a lower disease stage. Significant correlations were found more frequently in patients with EGFR mutations. Cell culture studies revealed that cancer cell-derived soluble factors induced PD-L2 overexpression in macrophages, suggesting the involvement of the JAK-STAT signaling pathway. The present findings suggest that PD-L2 expression in macrophages predicts PFS and CSS in lung adenocarcinoma without immunotherapy. [ABSTRACT FROM AUTHOR]

Programmed cell death-1 (PD-1) and PD-1 ligand 1 (PD-L1) are target molecules for immunotherapy in non-small cell lung cancer. PD-L1 is expressed not only in cancer cells, but also on macrophages, and has been suggested to contribute to macrophage-mediated immune suppression. We examined the clinical significance of PD-L1 expression on macrophages in human lung adenocarcinoma. The mechanism of PD-L1 overexpression on macrophages was investigated by means of cell culture studies and animal studies. The results showed that high PD-L1 expression on macrophages was correlated with the presence of EGFR mutation, a lower cancer grade, and a shorter cancer-specific overall survival. In an in vitro study using lung cancer cell lines and human monocyte-derived macrophages, the conditioned medium from cancer cells was found to up-regulate PD-L1 expression on macrophages via STAT3 activation, and a cytokine array revealed that granulocyte–macrophage colony-stimulating factor (GM-CSF) was a candidate factor that induced PD-L1 expression. Culture studies using recombinant GM-CSF, neutralizing antibody, and inhibitors indicated that PD-L1 overexpression was induced via STAT3 activation by GM-CSF derived from cancer cells. In a murine Lewis lung carcinoma model, anti-GM-CSF therapy inhibited cancer development via the suppression of macrophage infiltration and the promotion of lymphocyte infiltration into cancer tissue; however, the PD-L1 expression on macrophages remained unchanged. PD-L1 overexpression on macrophages via the GM-CSF/STAT3 pathway was suggested to promote cancer progression in lung adenocarcinoma. Cancer cell-derived GM-CSF might be a promising target for anti-lung cancer therapy. [ABSTRACT FROM AUTHOR]

Background: Right sleeve lower lobectomy is rarely performed because pulmonary function of the middle lobe is not spared to the extent of the other lobes and achieving a proper bronchial anastomosis is technically more difficult than other sleeve lobectomies. Case presentation: We performed four right sleeve lower lobectomies and had good clinical outcomes using specific technical options, such as telescope anastomosing, pericardiotomy, interlobar dissection between the upper and middle lobes, and angioplasty of the lower pulmonary artery, if needed. Conclusions: The cases presented herein demonstrated that a right sleeve lower lobectomy is one option by which to preserve the middle lobe using specific techniques and is thus recommended in select patients. [ABSTRACT FROM AUTHOR]

Purpose: Pleurodesis is performed in patients demonstrating air leakage after lung resection and in those with pneumothorax who must avoid surgery. However, there have so far been very few reports of pleurodesis with 50 % glucose. We herein examined the feasibility and effectiveness of this novel pleurodesis technique. Methods: Thirty-five patients after lung resection and 11 pneumothorax patients without surgery were treated with pleurodesis using 50 % glucose. Approximately, 200 mL of 50 % glucose solution was injected into the pleural space and repeated until the air leakage stopped. Cases in which the air leakage did not stop after three injections were considered to be unsuccessful and subsequently treated with conventional pleurodesis using OK-432. Results: Thirty-nine patients were successfully treated with 50 % glucose, although 7 patients required further treatment with OK-432. The unsuccessful group had some pulmonary comorbidities ( P < 0.001), and the pleural effusion volume after pleurodesis was less than that in the successful group ( P < 0.001). Although the air leakage did not stop in unsuccessful patients, the amount of air leakage markedly decreased. A temporary elevation of the blood sugar level was observed in 20 patients, but no other side effects had appeared. Conclusions: Pleurodesis with 50 % glucose is an easy, safe, and effective treatment modality. It is therefore considered to be a useful alternative method for pleurodesis. [ABSTRACT FROM AUTHOR]

Background: The detection rate of multiple lung adenocarcinomas, which display multiple ground glass opacity nodules in the peripheral lung, is increasing because of advances in high resolution computed tomography. The genetic backgrounds of multiple nodules and the mechanisms that underlie their multicentric development are unknown. In this study, we examined single nucleotide polymorphisms (SNPs) of the cytochrome P450 19A1 gene to determine if they are associated with multiple adenocarcinomas risk. Methods: Fifty-one cases of multiple adenocarcinomas with lepidic growth, 62 cases of a single adenocarcinoma with lepidic growth, and 126 control cases were analyzed. Three SNPs were analyzed by using a 5′ nuclease assay with TaqMan minor-groove-binder probe. The expression level of CYP19A1 in the noncancerous lung was quantified by real-time reverse transcription polymerase chain reaction (RT-PCR). Results: A minor allele of SNP rs3764221, which is located in the CYP19A1 gene, was significantly associated with multiple adenocarcinomas risk (adjusted odds ratio = 3.06; P = 0.006). Other polymorphisms of CYP19A1 were not significantly associated with the risk of multiple adenocarcinomas. A minor allele of SNP rs3764221 was also associated with a higher level of CYP19A1 messenger RNA expression ( P = 0.03). Conclusions: SNP rs3764221 contributes to the development of multicentric adenocarcinomas in the peripheral lung by causing higher levels of CYP19A1 expression. [ABSTRACT FROM AUTHOR]

The destruction of the basement membrane (BM) is the first step in cancer cell invasion and metastasis. Type IV collagen is a major component of the BM, and is composed of six genetically distinct α(IV) chains: α1(IV) to α6(IV). The loss of α5/α6(IV) chains from the epithelial BM at the early stage of cancer cell invasion has been reported in several cancers. However, the expression of α5/α6(IV) chains in esophageal squamous cell carcinoma (ESCC) remains unclear. The expression of α(IV) chains in 116 resected ESCC specimens was immunohistochemically examined. The role of α6(IV) chain was assessed in ESCC cell lines by short interfering RNA (siRNA). In intraepithelial carcinoma, the α5/α6(IV) chains were stained in a continuous linear pattern in the BM. In some cases of ESCC with the invasion beyond the lamina propria, the α5/α6(IV) chains were lost in the BM zone surrounding the cancer cell nests, but in other cases they remained. In the former, the disease-free survival and overall survival were significantly better than in those with the latter. The down-regulation of α6(IV) chain expression by siRNA revealed a slight increase of cancer cell invasiveness. The evaluation of α5/α6(IV) chains may be a useful marker for determining tumor cell properties, as a prognostic factor, in patients with ESCC. [ABSTRACT FROM AUTHOR]

The histological diagnosis of gastric intramucosal neoplastic lesions (GINLs) is controversial among experienced pathologists. Although the destruction of the epithelial basement membrane (BM) and the invasion of neoplastic epithelial cells into the interstitium of the lamina propria is distinct proof of “intramucosal carcinoma,” histological evaluation of GINLs is difficult and ambiguous, especially intestinal-type adenocarcinoma. Type IV collagen is a major component of the BM, and comprises six genetically distinct α(IV) chains, α1(IV) to α6(IV). In several types of carcinomas, the loss of α5/α6(IV) chains of the epithelial BM at an early invasive stage has been reported. However, the expression of α5/α6(IV) chains in GINLs is still unclear. We examined the immunohistochemical expression of α(IV) chains in GINLs and investigated whether the expression pattern was a diagnostic marker of gastric intramucosal carcinoma. The expression of α(IV) chains and Ki-67 in 60 resected GINL specimens was immunohistochemically examined. In normal gastric epithelium, α1(IV), α2(IV), α5(IV), and α6(IV) chains were expressed continuously in the BM. In most tubular adenomas (Japanese classification), these four chains were stained continuously in the BM, whereas in tubular adenocarcinomas (Japanese classification), the α5/α6(IV) chains had disappeared, partially or completely. The expression of α5/α6(IV) chains was closely related to the grade of histological atypia. In addition, the loss of α5/α6(IV) chains was significantly correlated with tumor cell growth activity. The loss of α5/α6(IV) chains might be a useful diagnostic finding for gastric intramucosal carcinoma in GINL cases. [ABSTRACT FROM AUTHOR]

Hepatocellular adenoma is a rare, benign neoplasm that is related to the use of contraceptives or androgenicanabolic steroids. A 51-year-old man with no history of steroid use was found to have a liver tumor. Plain computed tomography showed a high-density tumor that was enhanced in the arterial phase, and the enhancement was prolonged in the delayed phase. Magnetic resonance imaging showed that the tumor was hyperintense on in- and opposed-phase T1-weighted gradient recalled echo images and hyperintense on T1-weighted spin echo images. A partial hepatic resection was performed. A histological examination revealed normal hepatocyte-like tumor cells, composed of abundant dark brown granules of Dubin-Johnson-like pigment, which stained positively for Masson-Fontana stain. The tumor was diagnosed to be a very rare hepatocellular adenoma with the deposition of Dubin-Johnson-like pigment. [ABSTRACT FROM AUTHOR]

We performed extrapleural pneumonectomy (EPP) with combined resection of the diaphragm and pericardium via a lower door open (LDO) thoracotomy to treat right malignant pleural mesothelioma (MPM) in a 57-year-old man. Specifically, we extended the standard posterolateral thoracotomy skin incision along the anterior costal arch, and performed the thoracotomy by cutting into the 6th to 9th costal cartilage. The resulting defect of the diaphragm and pericardium were reconstructed with a reversed latissimus dorsi (LD) muscle flap and a fascia lata graft, respectively. The patient had an uneventful postoperative course without dyspnea or dysfunction of the extremities. The LDO thoracotomy provided a good operative field, especially for the costo- and cardiophrenic angles, allowing a complete resection of the diaphragm to be performed easily. Furthermore, the reversed LD muscle flap and fascia lata graft proved to be ideal autologous materials for reconstruction of both the diaphragm and the pericardium. [ABSTRACT FROM AUTHOR]