Bone morphogenetic protein-7 expression reflects the high proliferative ability and aggressiveness of thymic epithelial tumors.

BACKGROUND: Bone morphogenetic protein-7 (BMP-7) is a transforming growth factor-ß superfamily member. We examined whether BMP-7 expression in thymic epithelial tumors is associated with their clinicopathological features. METHODS: One hundred and thirty-two clinical specimens were analyzed in this study. The expression of BMP-7 was detected using immunohistochemistry and was scored as 0, 1, 2, or 3 according to its intensity and was then classified as negative (score 0 and 1) or positive (2 and 3). In addition, Ki-67 staining was performed in type B3 thymoma and thymic cancer. RESULTS: The positive ratio of BMP-7 was 80% in thymic cancer and 70% in thymoma type B3. In contrast, the positive ratios of BMP-7 in type B2 (29.1%), B1 (3.7%), AB (26%), and A (31%) were relatively low. The mean Ki-67 labeling index of the BMP-7 positive group (10.1%±5.9%) was significantly higher than that of the BMP-7 negative group (4.9%±5.9%) in type B3 thymoma and thymic cancer (P=0.012). The BMP-7 positive group showed significantly poorer overall survival (OS) than the BMP-7 negative group across all patients with thymic epithelial tumors and in all types of thymomas (P=0.006, P=0.018); however, no difference was observed in thymic cancers. CONCLUSIONS: This study showed that high expression of BMP-7 correlated with a poor prognosis in patients with thymic epithelial tumors, and the expression of BMP-7 was higher in type B3 thymomas and thymic cancers than in other types of thymomas. BMP-7 might serve as a novel prognostic biomarker for thymic epithelial tumors.

Interobserver size measurement variability in part-solid lung adenocarcinoma using pre-operative computed tomography.

BACKGROUND: In the current lung cancer tumor-node-metastasis classification, solid tumor size is used for tumor diameter measurement as the dense component. However, measuring solid tumor size is sometimes difficult and inter-observer variability may increase, particularly in part-solid nodules with ground-glass opacity (GGO). This study aimed to investigate inter-observer size measurement variability in lung adenocarcinoma. METHODS: Of 47 patients with part-solid lung adenocarcinoma who had undergone surgery at our department from January to December 2016, five surgeons and one radiologist undertook unidimensional solid and total size tumor measurements using pre-operative axial computed tomography images, and we assessed inter-observer size measurement variability. Variability was then subclassified into five groups, according to computer tomography-identified tumor morphological characteristics, namely: (I) minimally invasive; (II) peribronchovascular; (III) spiculation/atelectasis; (IV) adjacent to cystic lesion, and; (V) diffuse consolidation and GGO. RESULTS: The mean inter-observer variability was 9.7 mm (solid size) and 7.7 mm (total size). Analysis of the maximum and minimum measurement size values for each patient undertaken showed that the most experienced surgeon and the radiologist measured the minimum size more frequently. To correct for differences in mean tumor diameter in each group, a comparison was made using a coefficient of variation (CV) calculated as the ratio of the standard deviation to the mean. Group I characteristics showed the largest coefficient value for variation in solid size measurement. CONCLUSIONS: Inter-observer measurement variability for solid size was larger than for total size in lung adenocarcinoma. Large variability in group I indicated the difficulty of size measurement for low-grade malignant potential nodules such as adenocarcinoma in situ, minimally invasive adenocarcinoma, and early-stage invasive adenocarcinoma. The possibility of unavoidable size measurement variability should be recognized when deciding on surgical procedures for these diseases.

Development of angiosarcoma in a mediastinal non-seminomatous germ cell tumor that exhibited growing teratoma syndrome during chemotherapy.

Herein, we report a case of an angiosarcoma in a mediastinal non-seminomatous germ cell tumor that exhibited growing teratoma syndrome during chemotherapy. A 26-year-old man presented with a giant anterior mediastinal mass, which was diagnosed as a non-seminomatous germ cell tumor. The patient was administered three cycles of chemotherapy (bleomycin, etoposide, and cisplatin), but the mass grew despite normalization of tumor markers. Massive bleeding during thoracic surgery resulted in incomplete resection, and the mass was clinically and pathologically diagnosed as growing teratoma syndrome (only mature teratoma). The residual mass continued to grow, and complete resection was subsequently achieved after a detailed analysis of its vascular anatomy using angiography. The final pathological findings revealed angiosarcoma, which indicated a rare somatic type of mediastinal non-seminomatous germ cell tumor.

Primary mediastinal dedifferentiated liposarcoma: Five case reports and a review.

BACKGROUND: Liposarcoma has been subclassified histologically into well-differentiated, myxoid, pleomorphic, and dedifferentiated types. The dedifferentiated type generally shows poorer prognosis than the well-differentiated type. Because of its rarity, the clinicopathological features and clinical outcomes of primary mediastinal dedifferentiated liposarcoma remain unclear. METHODS: Five patients with primary mediastinal dedifferentiated liposarcoma were treated at Shinshu University Hospital between January 2012 and August 2017. We investigated the clinical characteristics, including age, gender, radiographic findings, pathological status, and clinical and treatment outcomes. RESULTS: Four of the five patients initially underwent radical surgical resection. One patient was disease-free after surgery, but the remaining three patients developed local recurrence in the mediastinum after surgical resection. Two of these patients underwent repeat surgical resection, resulting in long survival (60 and 40 months, respectively), while the other underwent proton beam therapy and showed no evidence of recurrence as of 17 months after treatment. The remaining patient was treated with chemotherapy using doxorubicin because of advanced inoperable disease, but failed to show a response and died within a month of the initiation of chemotherapy. Although the maximum standardized uptake values on fluorodeoxyglucose-computed tomography were relatively low, there was a slight positive relation between these values and the Ki-67-positive ratio in the tumor. CONCLUSION: Aggressive treatment by surgical resection should be considered for mediastinal dedifferentiated liposarcoma, even in cases with local recurrence.

Analysis of surgical treatment of Masaoka stage III-IV thymic epithelial tumors.

OBJECTIVE: The purpose of this study is to elucidate the outcomes after surgical resection of Masaoka stage III-IV thymic epithelial tumors. METHODS: We retrospectively reviewed patients with Masaoka stage III-IV thymic epithelial tumor who underwent surgical resection from January 1995 to January 2017. The clinicopathological features, surgical procedures, and postoperative outcomes were investigated. RESULTS: Thirteen patients with thymoma and 18 patients with thymic carcinoma were assessed. The postoperative Masaoka stages were III/IVa/IVb = 8/4/1 in thymoma and III/IVa/IVb = 11/2/5 in thymic carcinoma. In patients with thymoma, the World Health Organization pathological subtypes were A/B1/B2/B3 = 2/1/4/6. We performed combined resection and reconstruction for brachiocephalic vein or superior vena cava in 3 patients with thymoma and 7 patients with thymic carcinoma. In all patients, the patency rate of the grafts was very low for the left brachiocephalic vein and well maintained for the right brachiocephalic vein. Macroscopically and pathologically complete resection was achieved in 11 and 6 patients with thymoma, respectively, and in 15 and 9 patients with thymic carcinoma, respectively. The 10-year survival rates were 85.7% in thymoma and 70.3% in thymic carcinoma. Postoperative recurrences were observed in 2 and 9 patients with thymoma and thymic carcinoma, respectively. Recurrences were observed within 5 and 10 years after surgery in 2 patients with thymoma and within 2 years in all patients with thymic carcinoma. CONCLUSIONS: Patients with Masaoka stage III-IV thymic epithelial tumor showed relatively favorable long-term survival after surgical treatment. Therefore, aggressive surgical resection for complete resection may be a treatment option for these conditions.

Higher Tissue Levels of Thymidylate Synthase Determined by ELISA Are Associated with Poor Prognosis of Patients with Lung Cancer.

Thymidylate synthase (TS) is essential in thymidylate biosynthesis and DNA replication. Dihydropyrimidine dehydrogenase (DPD) is a rate-limiting enzyme in pyrimidine catabolism and is important in catabolism of 5-fluorouracil (5-FU). The significance of TS and DPD expressed in lung cancer remains controversial. Here we analyzed the relationship between TS and DPD expression and clinicopathological features of lung cancer. Enzyme-linked immunosorbent assays (ELISAs) were used to measure TS and DPD levels in paired tumor and non-tumor lung tissues obtained from 168 patients (107 adenocarcinomas, 39 squamous cell carcinomas, and 22 others), who had operations at the Shinshu University Hospital from 2004 to 2007 and were followed up for a median of 57.0 months. TS and DPD expression levels were higher in tumor tissues, and TS expression levels were significantly lower in adenocarcinomas than those in other subtypes. In addition, patients with low TS levels survived longer compared with patents with high TS levels. By contrast, DPD expression levels were not correlated with overall patient survival. Importantly, patients with low TS and DPD levels exhibited significantly prolonged survival than those with high TS and DPD. Among the 168 patients, 59 patients were treated with tegafur-uracil (UFT), a DPD-inhibitory fluoropyrimidine, and the UFT-treated patients with high TS and high DPD levels showed worst prognosis. Our study demonstrates a significant correlation between low TS expression levels and long-term prognosis of patients with lung cancer. Thus, ELISA is a clinically useful method to measure TS and DPD expression in lung cancer tissues.

Clinical significance of preoperative serum albumin level for prognosis in surgically resected patients with non-small cell lung cancer: Comparative study of normal lung, emphysema, and pulmonary fibrosis.

OBJECTIVES: This study was performed to clarify whether preoperative serum albumin level is related to the prognosis of non-small cell lung cancer patients undergoing surgical resection, and the relationships between serum albumin level and clinicopathological characteristics of lung cancer patients with emphysema or pulmonary fibrosis. MATERIALS AND METHODS: We retrospectively evaluated 556 patients that underwent surgical resection for non-small cell lung cancer. The correlation between preoperative serum albumin level and survival was evaluated. Patients were divided into three groups according to the findings on chest high-resolution computed tomography (normal lung, emphysema, and pulmonary fibrosis), and the relationships between serum albumin level and clinicopathological characteristics, including prognosis, were evaluated. RESULTS: The cut-off value of serum albumin level was set at 4.2g/dL. Patients with low albumin levels (albumin <4.2) had significantly poorer prognosis than those with high albumin levels (albumin ≥4.2) with regard to both overall survival and recurrence-free survival. Serum albumin levels in the emphysema group (n=48) and pulmonary fibrosis group (n=45) were significantly lower than that in the normal lung group (n=463) (p=0.009 and <0.001, respectively). Low serum albumin level was a risk factor in normal lung and pulmonary fibrosis groups, but not in the emphysema group. CONCLUSION: Preoperative serum albumin level was an important prognostic factor for overall survival and recurrence-free survival in patients with resected non-small cell lung cancer. Divided into normal lung, emphysema, and pulmonary fibrosis groups, serum albumin level showed no influence only in patients in the emphysema group.

Successful Resection of G719X-Positive Pleomorphic Carcinoma after Afatinib Treatment.

We report a case of pleomorphic carcinoma with exon 18 mutation (G719X) of the epidermal growth factor receptor (EGFR), which showed good response to afatinib and resulted in successful resection. To our knowledge, this is the first report on the use of afatinib for pleomorphic carcinoma followed by the surgical resection. The patient was a 59-year-old woman, who visited our hospital because chest computed tomography showed a 28 × 28-mm nodule in the left upper lobe. Bronchoscopy was performed and the histological findings of transbronchial biopsy revealed adenosquamous carcinoma positive for G719X mutation in exon 18 of the EGFR. Since fluorodeoxyglucose (FDG)-positron emission tomography/computed tomography revealed a positive accumulation in the bilateral hilar and mediastinal lymph nodes, the disease was diagnosed as cT1bN3M0, stage IIIB. After 3 months of afatinib therapy, FDG accumulation in primary tumor was almost gone. However, FDG accumulation in lymph nodes remained unchanged. Video-assisted thoracic surgery was planned for further diagnostic information and left upper lobectomy with mediastinal lymph node dissection was performed. The resected tumor included adenocarcinoma, squamous cell carcinoma, and spindle cell components, without lymph node metastasis. Thus, the disease was diagnosed as pleomorphic carcinoma (pT2aN0M0, stage IB). All components in the resected specimen had the same G719X mutation in exon 18 of the EGFR. The patient has shown no signs of recurrence at 1 year after the operation. The present case indicates the possibility of minor EGFR mutations in pleomorphic carcinoma and successful outcome by the use of afatinib and surgical resection.

Adjuvant surgical treatment of nontuberculous mycobacterial lung disease.

BACKGROUND: According to the 2007 American Thoracic Society/Infectious Diseases Society of America statement on nontuberculous mycobacterial diseases, more evidence for the benefits of adjuvant nontuberculous mycobacterial lung disease surgical intervention is needed before its wide application can be recommended. METHODS: A retrospective review was conducted of 60 consecutive patients who met American Thoracic Society/Infectious Diseases Society of America diagnostic criteria and underwent pulmonary resection for localized nontuberculous mycobacterial lung disease between January 2007 and December 2011. All patients were receiving chemotherapy before resection. RESULTS: Included were 41 women (68%) and 19 men (32%), with a median age of 50 years (range, 20 to 72 years). Of these, 55 patients (92%) had Mycobacterium avium complex disease. Bronchiectatic disease was noted in 29 patients, cavitary disease in 25, both in 4, and nodular disease in 2. The indications for resection were a poor response to drug therapy in 52 patients, hemoptysis in 6, and a secondary infection in 2. Sixty-five pulmonary resections were performed: 1 pneumonectomy, 3 bilobectomies, 39 lobectomies, 17 segmentectomies, 3 lobectomies plus segmentectomies, and 2 wedge resections. There were no operative deaths, and all patients attained sputum-negative status postoperatively. Eleven postoperative complications occurred in 8 patients (12%); relapse was observed in only 2 (3%). CONCLUSIONS: Pulmonary resection combined with chemotherapy is safe, with favorable treatment outcomes, for patients with localized nontuberculous mycobacterial lung disease. Our results support the liberal use of operations for nontuberculous mycobacterial lung disease whenever indicated.

Association of nuclear YB-1 localization with lung resistance-related protein and epidermal growth factor receptor expression in lung cancer.

BACKGROUND: Y-box binding protein 1 (YB-1) is an oncogenic transcription factor that is activated in response to various genotoxic stresses. The purpose of this study was to elucidate whether YB-1 correlates with the expression of lung resistance-related protein (LRP) and epidermal growth factor receptor (EGFR) in primary lung cancer. PATIENTS AND METHODS: One hundred and five non-small-cell lung cancer (NSCLC) specimens were analyzed by immunohistochemistry. Knockdown of YB-1 messenger RNA by small interfering RNA(siRNA) was tested for the lung cancer cell lines A549 and Calu-3. RESULTS: Nuclear YB-1 expression significantly correlated with positive LRP and EGFR expression (P < .001). Nuclear YB-1 expression and positive LRP and EGFR expression were independent adverse prognostic factors in patients with NSCLC. Furthermore, patients with tumors positive for nuclear YB-1 and LRP had a significantly worse prognosis than those negative for nuclear YB-1 and LRP (P < .001). In addition, patients with tumors positive for nuclear YB-1 and EGFR had a significantly worse prognosis than those negative for nuclear YB-1 and EGFR (P < .001). In in vitro analyses that use the NSCLC cell lines A549 and Calu-3, the downregulation of YB-1 with siRNAs drastically decreased the expression of EGFR. However, downregulation of YB-1 remarkably decreased the expression of LRP in A549 cells; however, a slight decrease in LRP was induced by the downregulation of YB-1 in Calu-3 cells. CONCLUSION: Our data demonstrate that nuclear YB-1 localization is associated with LRP and EGFR expression in NSCLC, and nuclear YB-1 localization and LRP and EGFR expression are of prognostic significance in NSCLC.

Risk factors that affect the surgical outcome in the management of focal bronchiectasis in a developed country.

BACKGROUND: The purpose of this study was to demonstrate our surgical experience for focal bronchiectasis in the setting of modern diagnostic modalities and state-of-the-art medical treatment in a developed country. METHODS: Thirty-one patients undergoing 33 lung resections for the treatment of focal bronchiectasis from 1991 to 2009 were reviewed. The mean age was 54 years. Twenty-nine patients (94%) were female; 21 patients (68%) had nontuberculous mycobacterial infection; and 22 patients (71%) received preoperative multiple-drug regimens containing clarithromycin. Five patients (16%) were in an immunocompromised status. All were diagnosed by chest computed tomography scan, and either the right middle lobe or left lingula were involved in 29 (94%). The curve for relapse-free interval was estimated by Kaplan-Meier methods. The factors that affected this curve were examined using Cox's regression analysis. RESULTS: Operative morbidity and mortality were 18% and 0%, respectively. All patients became asymptomatic postoperatively. During the median follow-up of 48 months (11 to 216), 8 patients (26%) experienced recurrence, and the mean relapse-free interval was 34 months (3 to 216). By univariate analysis, an immunocompromised status (p=0.017), Pseudomonas aeruginosa infection (p=0.040), the preoperative extent of bronchiectatic lesion (p=0.013), and the extent of residual bronchiectasis after surgery (p=0.003) were significantly associated with the shorter relapse-free interval. By multivariate analysis, an immunocompromised status (p=0.039), Pseudomonas aeruginosa infection (p=0.033), and the extent of residual bronchiectasis (p=0.009) were independent and significant factors. CONCLUSIONS: Complete resection of bronchiectasis while the disease is localized and is free from Pseudomonas aeruginosa infection is the key for a success. Also, immunocompromised status was suggested to be a risk factor.

A mediastinal somatic-type germ cell tumor with hepatic metastasis successfully treated by multiple modalities.

Rhabdomyosarcoma in the mediastinum coexisting with metastatic non-seminomatous germ cell tumor, so-called somatic-type malignancy, is a rare carcinoma and has poor survival. This study reports a case of diffuse and huge hepatic metastasis of non-seminomatous germ cell tumor associated with coexisting embryonal rhabdomyosarcoma in the mediastinum. A 31-year-old man presented with abdominal pain and was found to have multiple abnormal hepatic masses on abdominal computed tomography (CT). Concomitantly, an anterior mediastinal mass was found on chest CT. Chemotherapy was initiated because the hepatic lesion was diagnosed as choriocarcinoma, based on histological findings and the elevation of chorionic gonadotropin ß-subunit and α-fetoprotein. After six cycles of bleomycin, etoposide and cisplatin chemotherapy the metastatic liver tumors showed complete response. The remaining mediastinal tumor was completely and successfully resected. The histological findings revealed mature teratoma with embryonal rhabdomyosarcoma. The patient has remained well for over six years after the treatment without any signs of disease recurrence.

Intraoperative ultrasonographic localization of pulmonary ground-glass opacities.

OBJECTIVES: Ground-glass opacities are typically difficult to inspect and to palpate during video-assisted thoracic surgery. We therefore examined whether ultrasonographic assessments could localize ground-glass opacities and help to achieve adequate resection margins. METHODS: An intraoperative ultrasonographic procedure was prospectively performed on 44 patients harboring ground-glass opacities of less than 20 mm in diameter to localize these lesions and to achieve adequate margins. We also examined whether there were any complications resulting from the intraoperative ultrasonogram, such as lung injury, heart injury, or arrhythmia. We excluded patients with both asthma and chronic obstructive pulmonary disease from this study inasmuch as the intraoperative ultrasonographic procedure is more difficult to interpret when residual air is present in the lung. RESULTS: A total of 53 ground-glass opacities were successfully identified by intraoperative ultrasonography without any complications. Of the 20 mixed ground-glass opacities that we examined, 15 were found on palpation. However, only 4 (12.1%) of the 33 pure ground-glass opacities could be palpated. In all instances in which complete collapse of the lung was achieved (30/53 of these cases), high-quality echo images were obtained. Additionally, a strong correlation was found between the resection margins measured by ultrasonogram and the margins determined by histologic examination in the resected lung specimens (r(2) = 0.954, P < .001). CONCLUSIONS: Intraoperative ultrasonography can both safely and effectively localize pulmonary ground-glass opacities in a completely deflated lung. This procedure is also useful for the evaluation of surgical margins in a resected lung. Hence, ultrasonography may assist surgeons to perform minimally invasive lung resections with clear surgical margins during the treatment of solitary lung ground-glass opacity.

A subtotal sternectomy successfully reconstructed with composix mesh.

Sternal tumors are uncommon, which often require extended resections with reconstructions. Various techniques have been used, including a choice of prostheses and the use of musculocutaneous flaps for reconstructions. A 74-year-old male presented with a metastatic sternal tumor. He underwent a subtotal sternectomy with partial resection of bilateral clavicles and ribs. A sternal reconstruction was performed with Composix mesh and pectoralis major (PM) muscle flaps. This prosthesis was thought to be very suitable due to the ease of handling, good stability, and prevention of adhesion. In comparison to conventional prostheses, these points could be advantageous.

Castleman's disease arising from the chest wall.

An 18-year-old man was referred to our hospital because of an abnormality on chest radiography. Computed tomography showed a sharply defined, 5 x 2 x 3 cm, densely enhanced mass in the left side of the chest wall. We performed tumor resection under video-assisted thoracoscopy, with minimal bleeding. Histologically, the tumor was shown to be Castleman's disease. This is the eleventh case of Castleman's disease arising from the chest wall reported over the last 20 years.