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Pulmonary Langerhans cell histiocytosis (PLCH) is a subtype of Langerhans cell histiocytosis, a rare neoplastic disease characterized by lung involvement. Here, we present a case involving a patient with multiple cavitary nodules who was diagnosed with PLCH during surveillance after lung cancer surgery. A 74‐year‐old woman underwent right upper lobe resection surgery for right upper lobe lung adenocarcinoma, pStage IIA, 5 years ago. The patient underwent surveillance without adjuvant chemotherapy. During the fifth year of follow‐up, multiple nodules with cavitation were observed on computed tomography in both lung fields. Chemotherapy was considered to address the suspected recurrence of lung cancer; however, video‐assisted thoracoscopic surgery was performed due to the need for biomarker testing. Pathological examination led to the diagnosis of PLCH. This case emphasizes the importance of a proactive histological diagnosis to determine the appropriate treatment strategy, even in situations where lung cancer recurrence is clinically suspected. [ABSTRACT FROM AUTHOR]

Sphingolipids make up a family of molecules associated with an array of biological functions, including cell death and migration. Sphingolipids are often altered in cancer, though how these alterations lead to tumor formation and progression is largely unknown. Here, we analyzed non-small-cell lung cancer (NSCLC) specimens and cell lines and determined that ceramide synthase 6 (CERS6) is markedly overexpressed compared with controls. Elevated CERS6 expression was due in part to reduction of microRNA-101 (miR-101) and was associated with increased invasion and poor prognosis. CERS6 knockdown in NSCLC cells altered the ceramide profile, resulting in decreased cell migration and invasion in vitro, and decreased the frequency of RAC1-positive lamellipodia formation while CERS6 overexpression promoted it. In murine models, CERS6 knockdown in transplanted NSCLC cells attenuated lung metastasis. Furthermore, combined treatment with L-α-dimyristoylphosphatidylcholine liposome and the glucosylceramide synthase inhibitor D-PDMP induced cell death in association with ceramide accumulation and promoted cancer cell apoptosis and tumor regression in murine models. Together, these results indicate that CERS6-dependent ceramide synthesis and maintenance of ceramide in the cellular membrane are essential for lamellipodia formation and metastasis. Moreover, these results suggest that targeting this homeostasis has potential as a therapeutic strategy for CERS6- overexpressing NSCLC., Introduction Recent evidence has shown altered levels of biologically active sphingolipids and enzymes related to sphingolipid metabolism in cancer, indicating roles for these pathways in cancer pathogenesis and progression (1). [...]

Original citation: J Clin Invest. 2016;126(1):254-265. https://doi.org/10.1172/JCI79775. Citation for this retraction: J Clin Invest. 2019;129(11):5050. https://doi.org/10.1172/JCI133806. At the request of the corresponding author, the JCI is retracting this article. Following [...]

OBJECTIVES The purpose of this study was to elucidate the detectability of recurrence and the prognostic significance of the serum carcinoembryonic antigen (CEA) levels in patients with completely resected non-small-cell lung cancer (NSCLC). METHODS Five hundred and eighteen NSCLC patients who underwent complete resection at Aichi Cancer Center between April 2001 and March 2006 were enrolled in this study. The patient characteristics were as follows: the median age was 63 years; 331 tumours were classified as pathological stage I, 88 tumours were pathological stage II and 99 tumours were pathological stage III; 140 tumours were adenocarcinomas with epidermal growth factor receptor (EGFR) mutations, 268 tumours were adenocarcinomas with EGFR wild-type mutations and 110 tumours were other NSCLCs. The patients were divided into three groups: those with a normal CEA level before and 1–3 months after surgery (N group, n = 380), those with an elevated CEA level before surgery and a normal CEA level 1–3 months after surgery (HN group, n = 105) and those with an elevated CEA level 1–3 months after surgery regardless of the preoperative CEA level (H group, n = 33). The correlations between the changes in the serum CEA levels and the clinical outcomes were analysed. RESULTS Recurrence developed in 122 patients (32%) in the N group, 49 patients (47%) in the HN group and 19 patients (58%) in the H group (P = 0.001). The sensitivity and specificity of an elevated serum CEA level during the follow-up period for detecting recurrence were 30 and 98% in the N group and 82 and 73% in the HN group, respectively. Twenty-seven asymptomatic recurrent tumours combined with an elevated serum CEA level were detected in the HN group. In the multivariate Cox regression analysis, the serum CEA level 1–3 months after surgery had prognostic value for overall survival. CONCLUSIONS In completely resected NSCLC patients, measuring the serum CEA level during the follow-up period is useful in patients in whom an elevated level normalizes after surgery, and the serum CEA level 1–3 months after surgery is considered to have prognostic significance regarding survival. [ABSTRACT FROM AUTHOR]

OBJECTIVES Surgical resection is widely accepted as a beneficial treatment of pulmonary metastases originating from osteogenic and soft tissue sarcomas despite adequate validation. The factors associated with the selection of patients who receive pulmonary metastasectomy (PM) are controversial and not well known. In this study, we aimed to identify the prognostic factors associated with survival after treatment with PM and to disclose the candidates who profit from PM being performed on patients with osteogenic and soft tissue sarcomas. METHODS We retrospectively reviewed the variables and survival outcomes in 52 consecutive patients who underwent PM to treat lung metastases originating from osteogenic and soft tissue malignancies from April 1996 to January 2011. Prognostic factors associated with overall survival after the first PM were evaluated using univariate and multivariate analyses. RESULTS Fifty-eight PM procedures were performed in 52 patients as the first PM including 6 bilateral diseases. Wedge resection was the most frequently performed PM procedure (84%), and video-assisted thoracic surgery was introduced in 34 (59%). The median follow-up of the patients was 33 months and the 5-year survival rate after the first PM was 50.9%. Forty-eight (92%) patients underwent complete resection during the first PM. Thirty-three patients (62%) experienced relapse after the first PM. Among those patients, 20 received redo surgeries for pulmonary relapse, and the 5-year survival rate in this group was 49.7%. According to univariate analyses, the use of complete resection, the number of metastatic nodules (one or two) and the length of the disease-free interval prior to the first PM were each found to be significant favourable factors. According to a multivariate analysis, the use of complete resection and the number of metastatic nodules were both found to be independent prognostic factors associated with overall survival. Although our cohort included 15 patients with poor prognostic factors (29%), 5 patients who underwent redo surgery survived >22 months. CONCLUSIONS The survival of those patients with one or two pulmonary nodules and those who underwent complete resection was favourable following the treatment of osteogenic and soft tissue sarcomas with PM. Redo surgery may also provide some survival benefit in patients with poor prognostic factors. [ABSTRACT FROM AUTHOR]

Lysophosphatidic acid (LPA) is one of the simplest natural phospholipids. This phospholipid is recognized as an extracellular potent lipid mediator with diverse effects on various cells. Although LPA is shown to stimulate proliferation and motility via LPA receptors, LPA1 and LPA2, in several cancer cell lines, the role of LPA and LPA receptors for malignant pleural mesothelioma (MPM) has been unknown. MPM is an aggressive malignancy with a poor prognosis and the incidence is increasing and is expected to increase further for another 10–20 years worldwide. Therefore, the development of novel effective therapies is needed urgently. In this study, we investigated the effect of LPA on the proliferation and motility of MPM cells. We found that all 12 cell lines and four clinical samples of MPM expressed LPA1, and some of them expressed LPA2, LPA3, LPA4 and LPA5. LPA stimulated the proliferation and motility of MPM cells in a dose-dependent manner. Moreover, LPA-induced proliferation was inhibited by Ki16425, an inhibitor of LPA1, and small interfering RNA against LPA1, but not LPA2. Interestingly, LPA-induced motility was inhibited by small interfering RNA against LPA2, but not LPA1, unlike a number of previous reports. These results indicate that LPA is a critical factor on proliferation though LPA1, and on motility though LPA2 in MPM cells. Therefore, LPA and LPA receptors, LPA2 as well as LPA1, represent potential therapeutic targets for patients with MPM. ( Cancer Sci 2008; 99: 1603–1610) [ABSTRACT FROM AUTHOR]

Solitary fibrous tumour (SFT) is a mesenchymal neoplasm of subendothelial origin that can be found in all anatomical locations, but rarely in the lungs. A 71-year old female was referred to our hospital because of the increase in size of a solitary pulmonary mass. Chest contrast-enhanced dynamic computed tomography showed a well-circumscribed lobulated mass measuring 3.1 × 1.6 cm in the posterior segment of the right upper lobe of the lung. Positron emission tomography with 18F-fluorodeoxyglucose (FDG) demonstrated that the mass had high FDG uptake. A right upper lobectomy of the lung and mediastinal lymphadenectomy were performed. The tumour was pathologically diagnosed as an SFT. Seven months later, the patient was found to have brain metastases of the tumour, which led to dizziness. A craniotomy and successive radiosurgery with a gamma knife were performed for the metastatic tumours. She is still alive without evidence of disease 12 months after the treatment of the metastases. Pulmonary SFT seldom behaves aggressively, and only two previous cases of primary pulmonary SFT with brain metastases have been reported. Local therapy including surgery and radiotherapy against metastases from SFT could help improve the survival of such patients. [ABSTRACT FROM PUBLISHER]

Two photographs of an intrathoracic mass suspected of originating in themediastinum on three-dimensional computed tomography (3D-CT) angiography and contrast-enhanced computed tomography.

OBJECTIVES Positron emission tomography using [18F]-fluoro-2-deoxy-d-glucose (18F-FDG-PET) plays an important role in many oncological settings. In this study, we assessed the utility of 18F-FDG PET-CT for predicting the histologic type and stage of thymic epithelial tumours. METHODS We retrospectively analyzed 58 patients with thymic epithelial tumours who underwent PET–CT before treatment and investigated the relationship between the histologic type based on the World Health Organization classification and the maximum standardized uptake value (SUVmax) of each tumour. We also analyzed the relationship between the Masaoka tumour stage and the SUVmax. RESULTS The study included 31 males and 27 females, ranging in age from 25 to 80 years (median: 62 years). The tumour histology of 44 tumours was thymoma and that of the remaining tumours was thymic carcinoma, including 11 squamous cell carcinomas and 3 carcinoids. The Masaoka tumour stage was as follows: Stage I in 8, Stage II in 24, Stage III in 18 and Stage IV in 8 patients. The patients were divided into three groups according to a simplified histologic classification: low-risk thymomas (types A, AB and B1, n = 23), high-risk thymomas (types B2 and B3, n = 21) and thymic carcinomas (n = 14). The SUVmax of the thymic carcinoma group was significantly higher than those of the low-risk thymoma and high-risk thymoma groups (P < 0.001, respectively). No significant differences between the low-risk thymoma and high-risk thymoma groups were observed (P = 0.204). The SUVmax of Stages III and IV thymomas showed a higher trend toward Stages I and II thymomas (P = 0.060). CONCLUSIONS PET–CT is a useful modality for predicting the histologic type and tumour stage of thymic epithelial tumours. [ABSTRACT FROM AUTHOR]