Pleural Invasion Depth of Disseminated Nodules in Patients with Stage IVa or Recurrent Thymoma: Assessment, Curative Impact, and Surgical Outcomes.

BACKGROUND: Thymoma patients with pleural dissemination are difficult to manage, and their treatment strategy remains undefined. This study aimed to investigate the clinicopathologic features of these patients, focusing on the association between the depth of pleural invasion and prognosis. METHODS: Between 2003 and 2019, the study identified 120 disseminated lesions in 20 thymoma patients. Seven patients had de novo stage IVa thymoma and 13 were recurrent cases. Extrapleural pneumonectomy was performed for 8 patients and debulking surgery for 12 patients. Invasion depth of pleural tumors was classified into two groups: when the disseminated tumors invaded the pleura beneath the elastic layer, the tumor was diagnosed as Da, and when the disseminated tumors invaded the pleura beyond the elastic layer, the tumor was diagnosed as Db. RESULTS: Of 120 nodules, 31 (26%), found in eight patients with recurrent malignancies, were classified as Db. The pathologic status of the surgical margin (PSM) was positive in eight patients, seven of whom had Db nodules. The 5-year overall survival (OS) rate was 100% in the Da group and 75% in the Db group (P = 0.02). The 5-year progression-free survival (PFS) rate was 66.7% in the Da group and 25% in the Db group (P = 0.02). Cox univariate analysis showed that PFS was significantly influenced by the depth of invasion (P = 0.04) and PSM (P = 0.03). CONCLUSION: Depth of pleural invasion may influence survival outcomes for thymoma patients with pleural dissemination. The patients in this study with Da-disseminated nodules had an increased probability of a longer OS and PFS and tended to achieve negative PSM compared with the patients with Db.

CEBPγ facilitates lamellipodia formation and cancer cell migration through CERS6 upregulation.

Ceramide synthase 6 (CERS6) promotes lung cancer metastasis by stimulating cancer cell migration. To examine the underlying mechanisms, we performed luciferase analysis of the CERS6 promoter region and identified the Y-box as a cis-acting element. As a parallel analysis of database records for 149 non-small-cell lung cancer (NSCLC) cancer patients, we screened for trans-acting factors with an expression level showing a correlation with CERS6 expression. Among the candidates noted, silencing of either CCAAT enhancer-binding protein γ (CEBPγ) or Y-box binding protein 1 (YBX1) reduced the CERS6 expression level. Following knockdown, CEBPγ and YBX1 were found to be independently associated with reductions in ceramide-dependent lamellipodia formation as well as migration activity, while only CEBPγ may have induced CERS6 expression through specific binding to the Y-box. The mRNA expression levels of CERS6, CEBPγ, and YBX1 were positively correlated with adenocarcinoma invasiveness. YBX1 expression was observed in all 20 examined clinical lung cancer specimens, while 6 of those showed a staining pattern similar to that of CERS6. The present findings suggest promotion of lung cancer migration by possible involvement of the transcription factors CEBPγ and YBX1.

Diagnostic utility of metabolic parameters on FDG PET/CT for lymph node metastasis in patients with cN2 non-small cell lung cancer.

BACKGROUND: The aim of this study was to assess the diagnostic utility of metabolic parameters on fluorine-18-fluoro-2-deoxy-D-glucose-positron emission tomography (FDG-PET)/computed tomography (CT) for predicting lymph node (LN) metastasis in patients with cN2 non-small cell lung cancer (NSCLC). METHODS: We retrospectively reviewed patients who underwent surgery for cN2 NSCLC between 2007 and 2020. Those who had clinically diagnosed positive hilar and mediastinal LNs by routine CT and PET/CT imaging were investigated. To measure the metabolic parameters of LNs, the data according to maximum standardized uptake value (SUVmax), metabolic tumor volume (MTV), total lesion glycolysis (TLG), and LN-to-primary tumor ratio of SUVmax (LPR) were examined. The diagnosis of each retrieved LN was confirmed based on histopathological examination of surgical tissue specimens. Receiver operating characteristics (ROC) curves with area under the curve (AUC) calculations and multivariate analysis by logistic regression were performed. RESULTS: Forty-five patients with 84 clinically diagnosed positive hilar or mediastinal LNs were enrolled in the present study. Of the 84 LNs, 63 LNs were pathologically proven as positive (75%). The SUVmax, MTV, TLG, and LPR of LN metastasis were significantly higher than those of benign nodes. In the ROC analysis, the AUC value of LPR [AUC, 0.776; 95% confidence interval (CI), 0.640-0.913] was higher than that of LN SUVmax (AUC, 0.753; 95% CI, 0.626-0.880) or LN TLG3.5 (AUC, 0.746; 95% CI, 0.607-0.885). Using the optimal LPR cutoff value of 0.47, the sensitivity, specificity, positive predictive value, negative predictive value, and accuracy were 84.1, 66.7, 88.3, 58.3, and 79.8%, respectively. Multivariate analysis by logistic regression showed that LPR was an independent predictor for LN metastasis (odds ratio, 6.45; 95% CI, 1.785-23.301; P = 0.004). In the subgroup analysis of adenocarcinoma patients (n = 18; 32 LNs), TLG3.5 was a better predictor (AUC, 0.816; 95% CI, 0.639-0.985) than LPR (AUC, 0.792; 95% CI, 0.599-0.986) or LN SUVmax (AUC, 0.792; 95% CI, 0.625-0.959). CONCLUSIONS: Our findings suggest that LPR on FDG-PET is a useful predictor for LN metastasis in patients with cN2 NSCLC. TLG can be a good predictor for LN metastasis in patients with adenocarcinoma.

CERS6 required for cell migration and metastasis in lung cancer.

Sphingolipids constitute a class of bio-reactive molecules that transmit signals and exhibit a variety of physical properties in various cell types, though their functions in cancer pathogenesis have yet to be elucidated. Analyses of gene expression profiles of clinical specimens and a panel of cell lines revealed that the ceramide synthase gene CERS6 was overexpressed in non-small-cell lung cancer (NSCLC) tissues, while elevated expression was shown to be associated with poor prognosis and lymph node metastasis. NSCLC profile and in vitro luciferase analysis results suggested that CERS6 overexpression is promoted, at least in part, by reduced miR-101 expression. Under a reduced CERS6 expression condition, the ceramide profile became altered, which was determined to be associated with decreased cell migration and invasion activities in vitro. Furthermore, CERS6 knockdown suppressed RAC1-positive lamellipodia/ruffling formation and attenuated lung metastasis efficiency in mice, while forced expression of CERS6 resulted in an opposite phenotype in examined cell lines. Based on these findings, we consider that ceramide synthesis by CERS6 has important roles in lung cancer migration and metastasis.

Psoas muscle mass in patients undergoing lung cancer surgery: a prognostic difference between squamous cell carcinoma and adenocarcinoma.

BACKGROUND: Psoas muscle mass is a surrogate marker for sarcopenia: a depletion of skeletal muscle mass. This study was conducted to elucidate the prognostic significance of the psoas muscle index (PMI: cross-sectional area of the bilateral psoas muscle at the umbilical level on computed tomography/height2 [cm2/m2]) in patients undergoing surgery for lung squamous cell carcinoma (SCC) and lung adenocarcinoma (ADC). METHODS: One hundred and sixty-five patients with SCC and 556 patients with ADC who underwent R0 resection between 2007 and 2014 were reviewed for analysis. In SCC patients, the mean value (standard deviation) of the PMI was 6.15 (1.49) in men and 4.65 (1.36) in women. Among ADC patients, the PMI was 7.12 (1.60) in men and 5.29 (1.22) in women. Clinicopathological characteristics as well as the survival were evaluated. RESULTS: The PMI was associated with the age, body mass index (BMI), and serum albumin. In the multivariable Cox regression analysis, after adjusting for age, BMI, serum albumin, sex, pathological stage, and diffusing capacity for carbon monoxide, the PMI showed a significant association with the overall survival (OS) and disease-free survival (DFS) in SCC patients (hazard ratios 0.50 and 0.56, 95% confidence intervals 0.39-0.65 and 0.45-0.71, respectively). On the other hand, in ADC patients, the PMI had no impact on the OS or DFS. CONCLUSIONS: The PMI was significantly associated with the survival of lung SCC patients, but not of lung ADC patients, suggesting the presence of a previously unidentified relationship between skeletal muscle and lung SCC progression.

Verification of the diagnostic strategy for anterior mediastinal tumors.

BACKGROUND: For thymic epithelial tumors (TETs), the National Comprehensive Cancer Network guideline has suggested that complete excision of the tumor should be performed without a preoperative biopsy when resectable. However, little evidence has been provided to support this strategy. The purpose of this study was to review our diagnostic process and to evaluate the validity of radical resection of anterior mediastinal masses (AMMs) without pathological confirmation. METHODS: A total of 254 patients underwent surgical resection for AMMs between 2004 and 2015. This study included 181 patients with likely TETs according to clinical features, serum levels of tumor markers and autoimmune-antibodies, and radiological findings. In addition, AMMs likely TETs were classified into resectable or unresectable tumors. We retrospectively reviewed the diagnostic process of those patients and validated surgical resection of AMMs without a definitive diagnosis. RESULTS: Among 254 patients, 181 were suspected of having a TET based on the serum levels of tumor markers and autoimmune-antibodies and the radiological findings. Of them, 157 patients were deemed resectable and underwent surgical resection without histological confirmation, and 144 (92%) were diagnosed with TETs in the final pathological examinations. In 13 patients with non-TETs, the tumors were difficult to differentiate from TETs by imaging and clinical findings alone. CONCLUSIONS: A total of 92% of patients suspected of having a TET and who underwent complete resection without pathological confirmation were accurately diagnosed and properly treated. Surgical resection without a definitive diagnosis was feasible in patients suspected of having a TET when they were considered resectable.

Verification of T descriptor with consolidation size for sub-centimeter non-small cell lung cancer.

PURPOSE: In the most recent (eighth) edition of the TNM classification, the clinical T descriptor has been adapted to measure the consolidation size of sub-solid lung cancer. Sub-centimeter non-small cell lung cancer (NSCLC) has thereby been subclassified into three groups: Tis, T1mi, and T1a; however, the revision has not been validated well. Thus, we investigated the clinicopathological characteristics and long-term oncological outcomes of sub-centimeter NSCLCs based on the solid size. METHODS: The subjects of this retrospective review were 99 patients who underwent complete resection for NSCLC with ≤ 1 cm in consolidation size on computed tomography (CT). Survival was reanalyzed after reclassification according to the new TNM classification. RESULTS: This cohort consisted of 14 patients with cTis tumors, 18 with cT1mi tumors, and 67 with cT1a tumors. Among the patients with tumors classified as cT1a, two had lymph node metastasis and two had vascular invasion. The cumulative incidences of recurrence at 5 and 10 years were 0% for cTis/cT1mi tumors, and 4.5% and 6.1% for cT1a tumors, respectively. CONCLUSIONS: There may be pathological and survival differences between cTis/cT1mi tumors and cT1a tumors, but not between cTis tumors and cT1mi tumors.

The tumor doubling time is a useful parameter for predicting the histological type of thymic epithelial tumors.

PURPOSE: We assessed the utility of the tumor doubling time (TDT) for predicting the histological type of thymic epithelial tumors. METHODS: We retrospectively reviewed 130 patients with thymic epithelial tumors who underwent computed tomography two or more times before surgery. The patients were divided into low-risk thymoma (types A, AB and B1), high-risk thymoma (types B2 and B3) and thymic carcinoma (thymic carcinoma and thymic neuroendocrine tumor) groups. In the 96 patients who showed tumor enlargement, the relationship between the histological type and the TDT of the tumor was investigated. RESULTS: The study population included 55 men and 41 women from 26 to 82 years of age. The TDT of the thymic carcinoma group (median 205 days) was significantly shorter in comparison to the low-risk thymoma (median 607 days) and high-risk thymoma (median 459 days) groups. No significant differences were observed between the low-risk thymoma and high-risk thymoma groups. When we set the cutoff time for differentiating thymic carcinoma group from thymoma at 313 days, the sensitivity and specificity were 83.8% and 82.1%, respectively. CONCLUSIONS: The TDT is a useful parameter for differentiating between thymoma and thymic carcinoma group.

A survival analysis using physique-adjusted tumor size of non-small cell lung cancer.

BACKGROUND: Differences in individual body sizes have not been well considered when analyzing the survival of patients with non-small cell lung cancer (NSCLC). We hypothesized that physique-adjusted tumor size is superior to actual tumor size in predicting the prognosis. METHODS: Eight hundred and forty-two patients who underwent R0 resection of NSCLC between 2005 and 2012 were retrospectively reviewed, and overall survival (OS) was evaluated. The physique-adjusted tumor size was defined as: x-adjusted tumor size = tumor size × mean value of x/individual value of x [x = height, weight, body surface area (BSA), or body mass index (BMI)]. Tumor size category was defined as ≤2, 2-3, 3-5, 5-7, and >7 cm. The separation index (SEP), which is the weighted mean of the absolute value of estimated regression coefficients over the subgroups with respect to a reference group, was used to measure the separation of subgroups. RESULTS: The mean values of height, weight, BSA, and BMI were 160.7 cm, 57.6 kg, 1.59 m2, and 22.2 kg/m2, respectively. The 5-year survival rates ranged from 88-59% in the non-adjusted tumor size model (SEP 1.937), from 90-57% in the height-adjusted model (SEP 2.236), from 91-52% in the weight-adjusted model (SEP 2.146), from 90-56% in the BSA-adjusted model (SEP 2.077), and from 91-51% in the BMI-adjusted model (SEP 2.169). CONCLUSIONS: The physique-adjusted tumor size can separate the survival better than the actual tumor size.

A bilateral approach to extended thymectomy using the da Vinci Surgical System for patients with myasthenia gravis.

PURPOSE: We adopted a bilateral approach to complete robotic extended thymectomy with the excision of the pericardial fat tissue from both sides and analyzed the initial outcomes. METHODS: The patient cart was docked first from the left shoulder side. After dissection of the thymus and right pericardial fat tissue, the cart was temporarily rolled out, and the bed was rotated approximately 90° clockwise. The cart was then re-docked from the right-side shoulder, and extended thymectomy was performed via the left-side approach. The outcomes were compared with four cases of unilateral approach performed for mediastinal tumor in the same term. RESULTS: Four patients with myasthenia gravis (two of whom had stage I thymoma) underwent extended thymectomy by the bilateral approach. The mean operative time was 288 min, and the console time was 146 min in the right side and 67 min in the left side. The resected thymus and surrounding adipose tissue were almost symmetrical, in contrast with those obtained via the unilateral approach. No remarkable events were noted. CONCLUSION: Bilateral extended thymectomy for myasthenia gravis patients was safe and reasonable based on the initial outcomes.

Identification of proteasomal catalytic subunit PSMA6 as a therapeutic target for lung cancer.

To identify potential therapeutic targets for lung cancer, we performed semi-genome-wide shRNA screening combined with the utilization of genome-wide expression and copy number data. shRNA screening targeting 5043 genes in NCI-H460 identified 51 genes as candidates. Pathway analysis revealed that the 51 genes were enriched for the five pathways, including ribosome, proteasome, RNA polymerase, pyrimidine metabolism and spliceosome pathways. We focused on the proteasome pathway that involved six candidate genes because its activation has been demonstrated in diverse human malignancies, including lung cancer. Microarray expression and array CGH data showed that PSMA6, a proteasomal subunit of a 20S catalytic core complex, was highly expressed in lung cancer cell lines, with recurrent gene amplifications in some cases. Therefore, we further examined the roles of PSMA6 in lung cancer. Silencing of PSMA6 induced apoptosis or G2/M cell cycle arrest in cancer cell lines but not in an immortalized normal lung cell line. These results suggested that PSMA6 serves as an attractive target with a high therapeutic index for lung cancer.

The Role of 18F-fluorodeoxyglucose Positron Emission Tomography-Computed Tomography for Predicting Pathologic Response After Induction Therapy for Thymic Epithelial Tumors.

BACKGROUND: We investigated the role of 18F-fluorodeoxyglucose positron emission tomography-computed tomography (PET-CT) in predicting the effect of induction therapy in patients with thymic epithelial tumors. METHODS: Fourteen patients with thymic epithelial tumors who underwent PET-CT before and after induction therapy were retrospectively analyzed. The relationship between the change in the maximum standardized uptake value (SUVmax) in PET-CT, the response evaluation criteria in solid tumors and the pathologic response (Ef0, no necrosis of tumor cells; Ef1, some necrosis of tumor cells with more than one-third of viable tumor cells; Ef2, less than one-third of tumor cells were viable; and Ef3, no tumor cells were viable) was analyzed. RESULTS: The study cohort consisted of 5 males and 9 females. Nine of the patients had thymoma, and 5 had thymic carcinoma. The induction therapy included chemotherapy in 9 cases, chemoradiation therapy in 4 cases and radiation therapy in 1 case. Among the 8 patients with a pathologic response of Ef0/1, 5 were clinically evaluated as having stable disease (SD), while 3 were found to have had a partial response (PR). The SUVmax was elevated in 2 cases, unchanged in 1 and decreased in 5. On the other hand, 3 of the 6 patients with a pathologic response of Ef2, 3 were classified as having SD, while the other 3 had a PR. The SUVmax decreased in all of the patients. CONCLUSIONS: In comparison with CT, PET-CT seems to be useful for predicting the pathologic response to induction therapy in patients with thymic epithelial tumors.

Marginal pulmonary function is associated with poor short- and long-term outcomes in lung cancer surgery.

We sought to determine the short- and long-term prognoses among 'marginal-risk' non-small cell lung cancer patients who have a predicted postoperative- (ppo) forced expiratory volume in the first second (FEV1) of 30-60% and/or a ppo-diffusing capacity of the lung for carbon monoxide (DLCO) of 30-60%. The present study included 73 'marginal-risk' and 318 'normal-risk' patients who underwent anatomical resection for clinical stage I lung cancer between 2008 and 2012. The rates of postoperative morbidity, prolonged hospital stay, and overall survival were assessed. Postoperative morbidity occurred in 35 (48%) 'marginal-risk' patients and 66 (21%) 'normal-risk' patients, and 17 (23%) 'marginal-risk' patients and 20 (6%) 'normal-risk' patients required a prolonged hospital stay. The three- and five-year survival rates were 79% and 64% in the 'marginal-risk' patients and 93% and 87% in the 'normal-risk' patients, respectively. A 'marginal-risk' status was a significant factor in the prediction of postoperative morbidity (odds ratio [OR] 2.97, p < 0.001), the rate of prolonged hospital stay (OR 3.83, p < 0.001), and overall survival (hazard ratio 2.07, p = 0.028). In conclusion, 'Marginal-risk' patients, who are assessed based on ppo-values, comprise a subgroup of patients with poorer short- and long-term postoperative outcomes.

Growth rate of chemotherapy-naïve lung metastasis from colorectal cancer could be a predictor of early relapse after lung resection.

PURPOSE: The aim of this study was to elucidate a potential risk factor for early relapse after pulmonary metastasectomy of colorectal cancer and to propose an optimal treatment strategy for lung metastasis with an aggressive nature. METHODS: Seventy patients who underwent pulmonary metastasectomy for diachronically measurable pulmonary lesions were retrospectively analyzed. We calculated the tumor doubling time (TDT) as the growth rate of lung metastasis and divided the study population into two groups: Rapid (TDT ≤ 100 days) and Slow (TDT > 100 days). RESULTS: The patients consisted of 47 males and 23 females, with a mean age of 63 years. Forty-two patients had a relapse after pulmonary metastasectomy with a median follow-up duration of 24 months. There was a significant difference in relapse-free survival between the Rapid and Slow groups (p = 0.047). Using a multivariate analysis, no preoperative chemotherapy and a high level of serum carcinoembryonic antigen were proven to be significant risk factors for relapse after metastasectomy. Meanwhile, multivariate analyses among 37 patients without preoperative chemotherapy indicated that TDT was the sole significant factor for relapse-free survival. In addition, eight of nine patients with relapse within 12 months were placed into the Rapid group. CONCLUSIONS: Although this was a preliminary study with a small number of patients, it suggested that lung metastases demonstrating a TDT of 100 days or less have a high risk of early relapse after metastasectomy.

[New TNM Staging System for Thymic Malignancies].

In patients with malignant tumors, the TNM classification has been widely used by clinicians as a guide for estimating prognosis, and is the basis for treatment decisions. Recently, the International Association for the Study of Lung Cancer Staging and Prognostic Factors Committee and the International Thymic Malignancy Interest Group have proposed a new classification for thymic malignancies to be included in the next official staging system of the forthcoming 8th edition of the TNM classification. In this study, we reviewed 154 consecutive patients with thymic epithelial tumors who underwent complete resection at our institution, and compared their characteristics and outcomes when classified according to the proposed system with those when classified under the current Masaoka-Koga system. The proportion of patients with stage I disease increased markedly to 77.3% under the proposed system because a certain number of patients with Masaoka-Koga stages II and III diseases were downstaged to the new stage I. Regarding histology, among 69 patients with type A, AB, or B1 thymoma, 68 tumors (99%) were diagnosed as new stage I disease. When using the proposed system, the recurrence-free survival rates showed significant deterioration with increasing stage, while the overall survival rates did not. Although the new TNM classification does not serve as an effective prognostic prediction model for overall survival, it appears to offer some benefit, especially in the analysis of recurrence-free survival.

Micronodular thymoma with lymphoid stroma: an immunohistochemical study of the distribution of Langerhans cells and mature dendritic cells in six patients.

AIMS: Micronodular thymoma with lymphoid stroma (MNT) is an uncommon variant of thymoma, characterized by multiple small nodules consisting of type A thymoma-like cells, which are separated by abundant B lymphocytes. The aim of the study was to elucidate the pathogenesis of the stromal lymphoid hyperplasia, which is currently unclear. METHODS AND RESULTS: We retrieved six cases of MNT, and immunohistochemically examined the number and distribution of Langerhans cells (LCs) and mature dendritic cells (DCs), and compared them with those in type A and type AB thymomas. Many LCs were present within the small tumour nests, but LCs were rarely seen in the stroma (75.5/HPF versus 6.1/HPF, P < 0.0001). In contrast, mature DCs were present mainly in the surrounding stroma rather than within the tumour nodules (63.5/HPF versus 6.0/HPF, P < 0.0001), forming clusters with mature T lymphocytes adjacent to lymphoid follicles. In large nodules, as well as in type A and type AB thymomas, a few scattered LCs and DCs were identified. All patients were still alive and well. CONCLUSIONS: Our results suggest that LCs take up tumour antigens and migrate to the stroma, where they mature and form clusters with T lymphocytes to activate them, resulting in lymphoid follicle formation. The favourable clinical behaviour may be attributable to the immune response induced by LCs.

The ABO blood group is an independent prognostic factor in patients with resected non-small cell lung cancer.

BACKGROUND: The ABO blood group is reported to be associated with the incidence and patient survival for several types of malignancies. We conducted a retrospective study to evaluate the prognostic significance of the ABO blood group in patients with resected non-small cell lung cancer (NSCLC). METHODS: A total of 333 patients (218 men and 115 women) with resected NSCLC were included in this study. In addition to age, sex, smoking status, preoperative serum carcinoembryonic antigen (CEA) level, operative procedure, histology of tumors, pathological stage (p-stage), and adjuvant therapy, the association between the ABO blood group and survival was explored. RESULTS: The 5-year overall and disease-free survival rates were 83.0% and 71.6% for blood group O, 67.2% and 62.3% for blood group A, 68.8% and 68.8% for blood group B and 69.2% and 65.3% for blood group AB, respectively. A multivariate analysis for overall survival showed the ABO blood group (group A vs. group O: HR 2.47, group AB vs. group O: HR 3.62) to be an independent significant prognostic factor, in addition to age, sex, smoking status, p-stage, and serum CEA level. A multivariate analysis for disease-free survival also showed the ABO blood group to be an independent significant prognostic factor. CONCLUSIONS: The ABO blood group is an independent prognostic factor in patients with resected NSCLC. Studies of other larger cohorts are therefore needed to confirm the relationship between the ABO blood group and the prognosis among patients with resected NSCLC.

Which variables should be considered in patients with stage II and III non-small cell lung cancer after neoadjuvant therapy?

This study was designed to elucidate the predictive usefulness of the response evaluation criteria in solid tumors (RECIST), a volume response (VR; a > 50% reduction in the tumor volume) and the post-neoadjuvant therapy maximum standardized uptake value (post-SUVmax) in patients with non-small cell lung cancer (NSCLC) after neoadjuvant therapy. Between December 2006 and June 2012, 33 patients with clinical stage II and III NSCLC who underwent pulmonary resection following neoadjuvant therapy were enrolled. The relationships between the variables and a pathological complete response (pCR), the disease-free survival (DFS) and the overall survival (OS) were analyzed. As neoadjuvant therapy, 24 patients received chemoradiotherapy, five patients received chemotherapy and four patients were given radiation therapy. Based on the RECIST, 12 tumors were classified as having a partial response and 21 tumors were classified as stable disease. Twenty-one tumors showed a VR and 12 did not. Twenty-five tumors had a post-SUVmax ≤7.5 and eight had a post-SUVmax >7.5. Eight tumors had a pCR. In the multivariate Cox regression analysis, both a non-VR and a post-SUVmax >7.5 were significant variables predicting the DFS (p = 0.0422 and 0.0127, respectively), but either was not for OS. The post-SUVmax was also a significant variable for the pCR rate (p = 0.0067). The post-treatment SUVmax can be a valid alternative variable that can be used to predict the effect of neoadjuvant therapy and the survival of patients with stage II and III NSCLC.

Primary malignant melanoma of the thymus: report of a case.

A 61-year-old male was admitted to our hospital complaining of bloody sputum. A chest roentgenogram revealed a clearly demarcated mass located in the anterior mediastinum. Positron emission tomography revealed abnormal accumulation of (18)F-fluorodeoxy glucose only in the anterior mediastinal tumor. A computed tomography-guided needle aspiration biopsy was performed, and the tumor was diagnosed as a malignant melanoma. Although the skin, eyeballs, oral cavity, nasal cavity, etc., were closely evaluated, no other lesion of malignant melanoma was detected except the mediastinal tumor. Hence, this tumor was diagnosed as a primary malignant melanoma. We performed total thymectomy, including the tumor, and combined resection of the adhesive bilateral lungs, pericardium and left brachiocephalic vein. Because the tumor was histologically surrounded by thymus tissue, we diagnosed it as a primary mediastinal malignant melanoma that originated in the thymus. Although the patient's postoperative course was uneventful, he complained of back pain 5 months after the operation. Multiple bone metastases were found, and he received chemotherapy and radiotherapy, and is currently alive with disease 14 months after the primary treatment.

Preoperative plasma D-dimer level is an independent prognostic factor in patients with completely resected non-small cell lung cancer.

PURPOSE: The plasma D-dimer (D-dimer) level, a marker of hypercoagulation, has been reported to be associated with survival in several types of cancers. This retrospective study was conducted to evaluate the prognostic significance of the preoperative D-dimer level in patients with completely resected non-small cell lung cancer (NSCLC). METHODS: A total of 237 completely resected NSCLC patients were included in this study. In addition to age, sex, the smoking status, etc., the association between the preoperative D-dimer level and survival was explored. RESULTS: The patients were divided into three groups according to the D-dimer level: group A (≤ 0.50 µg/ml, n = 76), group B (0.51-0.86 µg/ml, n = 79) and group C (>0.86 µg/ml, n = 82). The 5-year overall survival rate was 89.6 % (95 % confidence interval (CI) 77.7-95.3) for group A, 75.1 % (95 % CI 62.3-83.6) for group B and 60.1 % (95 % CI 46.8-71.1) for group C (P trend <0.001). A multivariate survival analysis showed that the D-dimer level (group B vs. group A HR 4.25, group C vs. group A HR 4.11) was an independent significant prognostic factor, in addition to age, sex, the pathological stage and the serum carcinoembryonic antigen level. CONCLUSIONS: The preoperative D-dimer level is an independent prognostic factor in patients with completely resected NSCLC.