Thymic Mucoepidermoid Carcinoma: A Clinicopathologic and Molecular Study.

Thymic mucoepidermoid carcinoma (MEC) is a rare tumor, and its characteristics remain to be clarified. Here we investigated 20 cases of thymic MEC to systematically characterize its clinical, histopathologic, and molecular features. The median age of the patients was 56 years (range, 19 to 80 y), there was a slight male predilection (3:2), and 44% of the patients were asymptomatic at diagnosis. The median tumor size was 6.8 cm in diameter, 55% were pT1 tumors, and 50% were TNM stage I tumors. When 4 tumor grading systems for salivary MEC (Armed Forces Institutes of Pathology, Brandwein, modified Healey, and the Memorial Sloan-Kettering) were employed, low-grade, intermediate-grade, and high-grade tumors accounted for 35% to 70%, 5% to 25%, and 25% to 50%, respectively. Many histologic variants were noted, and 70% of the cases were classified as nonclassic variants. MAML2 rearrangement was detected in 56% of cases, and the fusion partner was CRTC1 in all cases. CRTC1-MAML2 fusion was associated with lower pT classification and lower TNM stage. The overall survival rate of all patients was 69% and 43% at 5 and 10 years, respectively. Worse overall survival was associated with higher pT stage, higher TNM stage, residual tumors, greater tumor size, high-grade tumor histology (Armed Forces Institutes of Pathology and Memorial Sloan-Kettering, but not the other 2), and with the absence of CRTC1-MAML2 fusion. Of note, none of the patients with CRTC1-MAML2 fusion-positive tumors died during the follow-up. In conclusion, the clinicopathologic and molecular findings of thymic MEC presented here are expected to contribute to the management of this rare tumor.

Postoperative chylothorax following lung cancer surgery with an aberrant course of thoracic duct: a case report.

Postoperative chylothorax occurs relatively rarely after pulmonary resections, often caused intraoperatively by injury to the thoracic duct. We describe a case of postoperative chylothorax after lung cancer surgery with an aberrant thoracic duct course. A 66-year-old man showed abnormal findings on chest computed tomography (CT) during health screening and was suspected with primary lung cancer. Then, he underwent a right upper lobectomy with mediastinal lymph-node dissection. The histopathological findings confirmed lung adenocarcinoma. However, the patient developed a postoperative chylothorax and underwent revision surgery. An abnormally running thoracic duct, which was expected to flow into the right venous angle, was found at the cranial side of the right superior mediastinal dissection area and was clipped. Considering the many variations in the route of the thoracic duct, thoracic surgeons should remain alert for postoperative chylothorax when performing lung cancer surgery with mediastinal lymph-node dissection and prepare treatment strategies accordingly.

[Bronchogenic Cyst with Rapid Increase and Emergency Operation;Report of a Case].

A 21-year-old man was admitted with fever and back pain. Chest computed tomography(CT) showed a cystic mass of 7×6 cm in the right middle mediastinum. After 3 days, symptoms worsen, and chest X-ray revealed the enlargement of the cyst, and an emergent operation was performed. Since the tumor was severely adhered to the superior vena cava and the azygous vein, the cystic mass was partially resected. The pathological diagnosis was bronchogenic cyst.

[Osimertinib Was Effective for Liver Metastasis after Surgery for Lung Cancer with Simultaneous Expression of EGFR L858Ra nd T790M Mutations-A Case Report].

A 63-year-old woman underwent right lower lobectomy and mediastinal dissection for lung cancer. At 5 years and 5 months after surgery, chest computed tomography revealed multiple liver metastasis. EGFR gene mutations of L858R and T790M were detected in both the primary lung cancer lesion and the liver metastasis specimen. Gefitinib was initiated as the first-line treatment, but the tumors increased in size. Osimertinib, as second-line treatment, was remarkably effective against the liver metastatic lesions and it maintained a partial response for approximately 1 year. Thus, osimertinib was effective for liver metastasis of lung cancer with EGFR mutations of L858R and T790M.

[Late-onset Chylothorax after Right Upper Lobectomy;Report of a Case].

Chylothorax after pulmonary resection is diagnosed usually within a few days after surgery, hence late-onset chylothorax is relatively rare complication. A 79-year-old woman underwent right upper lobectomy and mediastinal dissection for lung cancer. A chest tube was removed on postoperative day (POD)3, and she was discharged on POD 8. Fifty days after an operation, the patient developed a dyspnea on effort, and chest radiography revealed a right-sided pleural effusion, which we diagnosed as chylothorax. Because the treatments of a fat-free diet and subcutaneous octreotide acetate administration were ineffective, thoracic duct ligation was finally performed. The post-reoperative course was uneventful.

[Micronodular Thymoma with Lymphoid Stroma;Report of a Case].

We report a surgical case of micronodular thymoma with lymphoid stroma (MNT), which is a rare type of thymoma. A 66-year-old man was referred to our hospital for further examination and treatment of a nodule in the mediastinum. Computed tomography(CT) showed a 20-mm nodule in the anterior mediastinum, and positron emission tomography-CT showed slight uptake in the same region. Thymoma was suspected and videoassisted thymectomy was performed. Histopathological findings showed spindleshaped tumor cells forming storiform, with the background of lymphoid stroma, and the tumor was diagnosed as MNT. The long-term outcome after resection of MNT currently remains unclear, and accumulation of further cases is required.

Potential Role of ASC, a Proapoptotic Protein, for Determining the Cisplatin Susceptibility of Lung Cancer Cells.

Primary lung cancer is the most frequent cause of cancer-related deaths worldwide. Cisplatin has been used as a key drug in the treatment for patients with lung cancer; however, most of the patients failed to respond to cisplatin within several months, and the mechanisms underlying the cisplatin resistance have not been fully elucidated. Apoptosis-associated speck-like protein containing a caspase recruitment domain (ASC) is a key adaptor protein in the formation of inflammasomes. ASC is also involved in apoptotic signaling. Importantly, ASC expression is decreased in lung cancer and various cancers, but its precise function in tumor progression remains unknown. To explore the hitherto unknown role of ASC in lung cancer, we initially searched for lung cancer cell lines with higher expression levels of ASC using Cancer Cell Line Encyclopedia (CCLE) database, thereby identifying the A549 human non-small cell lung cancer cell line. Accordingly, with retroviral shRNA, the expression of ASC was forced to decrease in A549 cells. Stable ASC-knockdown cells, thus established, showed the increased activities of proliferation, motility, and invasion, compared with control cells. Importantly, ASC-knockdown cells also became resistant to cisplatin, but not to other anti-cancer agents, 5-fluorouracil and paclitaxel. Bcl-2 and phospho-Src levels were increased in ASC-knockdown cells. A Bcl-2 inhibitor, ABT-199, induced an apoptotic response in ASC-knockdown cells, and dasatinib, a Src inhibitor, blocked cell invasiveness. Thus, ASC may be involved in tumor suppression and cell death via Bcl-2 and pSrc. Targeting Bcl-2 and Src in ASC-downregulated populations of lung cancer may improve treatment outcome.

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.

The histological characteristics and clinical outcomes of lung cancer in patients with combined pulmonary fibrosis and emphysema.

Combined pulmonary fibrosis and emphysema (CPFE) is an important risk factor for lung cancer (LC), because most patients with CPFE are smokers. However, the histological characteristics of LC in patients with CPFE (LC-CPFE) remain unclear. We conducted this study to explore the clinicopathological characteristics of LC-CPFE. We retrospectively reviewed data from 985 patients who underwent resection for primary LC, and compared the clinicopathological characteristics of patients with LC-CPFE and non-CPFE LC. We identified 72 cases of LC-CPFE, which were significantly associated with squamous cell carcinoma (SqCC) histology (n = 46, P < 0.001) and higher tumor grade (n = 44, P < 0.001), compared to non-CPFE LC. Most LC-CPFE lesions were contiguous with fibrotic areas around the tumor (n = 59, 81.9%), and this association was independent of tumor location. Furthermore, dysplastic epithelium was identified in the fibrotic area for 31 (52.5%) LC-CPFE lesions. Moreover, compared to patients with pulmonary fibrosis alone in the non-CPFE group (n = 31), patients with CPFE were predominantly male (P = 0.008) and smokers (P < 0.001), with LC-CPFE predominantly exhibiting SqCC histology (P = 0.010) and being contiguous with the tumor-associated fibrotic areas (P < 0.001). Multivariate analysis revealed that CPFE was an independent predictor of overall survival (hazard ratio: 1.734; 95% confidence interval: 1.060-2.791; P = 0.028). Our results indicate that LC-CPFE has a distinct histological phenotype, can arise from the dysplastic epithelium in the fibrotic area around the tumor, and is associated with poor survival outcomes.

Development of combined thymic carcinoma and thymoma in an extrathymic lesion during long follow-up for recurrent thymoma.

The present study reported a rare case of combined thymic squamous cell carcinoma and thymoma exhibiting a mass on the left chest wall. The patient underwent thoracotomy for invasive thymoma 15 years previously, however, suffered a relapse in the left intrathoracic space. Radiotherapy, chemotherapy and partial resection, as secondary surgery for the intrathoracic mass, were performed. The histological findings in the resected specimens revealed type B3 thymoma. As the patient developed a left chest wall mass and pain in 2013, the mass was resected. The histological findings indicated two separate components composed of type B3 thymoma and squamous cell carcinoma. Immunohistological findings revealed that the thymoma cells were positive for CD5, while the thymic carcinoma cells were negative for CD5. Several reports have demonstrated the coexistence of thymic carcinoma and thymoma in the primary thymus, however, the development of a combined tumor in an extrathymic lesion is extremely rare. The present case had a long follow-up for recurrent thymoma. The present case indicated that the development and/or coexistence of malignant components in the thymoma must be taken into consideration for the treatment and/or management of patients with thymoma and that a pre-existence of CD5 expression in thymoma and the lost change may be associated with the process of malignant transformation.

Usefulness of vessel-sealing devices for ≤7 mm diameter vessels: a randomized controlled trial for human thoracoscopic lobectomy in primary lung cancer.

OBJECTIVES: Vessel-sealing devices (VSDs) are widely used for various surgical procedures, including thoracoscopic surgery, but very few reports have compared their safety and usefulness with human thoracoscopic lobectomy procedures not employing VSDs. METHODS: Primary lung cancer patients for whom a thoracoscopic lobectomy involving mediastinal lymph node dissection was planned in our department from April 2011 to March 2013 were recruited for the study. Patients were randomly allocated to a control group (n = 14) or a VSD group (n = 44), which comprised three sub-groups, namely EnSeal (n = 17), LigaSure (n = 15) and Harmonic (n = 12). The control group comprised patients undergoing surgery solely with ligation and conventional electrocautery. EnSeal, LigaSure and Harmonic were chosen because they are the three most popular disposable VSDs used in Japan. In the VSD groups, the proximal side of pulmonary artery stumps (≤7 mm diameter) were ligated and then treated with respective devices. Primary end-points were burst pressure of the pulmonary artery stump (measured using resected specimens), operative time, intraoperative blood loss, instances of endostapler use, intraoperative surgeon stress (assessed by visual analogue scale) and postoperative drainage volume and duration. As a secondary objective, the individual VSD groups were also compared with each other. RESULTS: The burst pressure of ligation-treated pulmonary artery stumps was higher than that of VSD-treated stumps (P <0.0001). The burst pressure of <5-mm-wide VSD-treated stumps was higher than that of ≥5-mm-wide stumps (P = 0.0421). However, the burst pressure for all groups and all vessel diameters was sufficient to withstand the physiological pulmonary artery pressure. The VSD group demonstrated reduced intraoperative blood loss (P = 0.0241), surgeon stress (P = 0.0002), postoperative drainage volume (P = 0.0358) and shortened postoperative drainage duration (P = 0.0449). Operative time and the instances of endostapler use did not significantly differ. Comparison between each of the VSD groups revealed no significant differences. None of the patients experienced serious perioperative complications or died because of surgery. CONCLUSION: VSD is simple and safe to use in thoracoscopic lobectomy involving mediastinal lymph node dissection for primary lung cancer. Furthermore, none of the VSDs used in this study presented any observable differences in quality that could lead to clinical problems.

Tumor size and computed tomography attenuation of pulmonary pure ground-glass nodules are useful for predicting pathological invasiveness.

OBJECTIVES: Pulmonary ground-glass nodules (GGNs) are occasionally diagnosed as invasive adenocarcinomas. This study aimed to evaluate the clinicopathological features of patients with pulmonary GGNs to identify factors predictive of pathological invasion. METHODS: We retrospectively evaluated 101 pulmonary GGNs resected between July 2006 and November 2013 and pathologically classified them as adenocarcinoma in situ (AIS; n = 47), minimally invasive adenocarcinoma (MIA; n = 30), or invasive adenocarcinoma (I-ADC; n = 24). The age, sex, smoking history, tumor size, and computed tomography (CT) attenuation of the 3 groups were compared. Receiver operating characteristic (ROC) curve analyses were performed to identify factors that could predict the presence of pathologically invasive adenocarcinomas. RESULTS: Tumor size was significantly larger in the MIA and I-ADC groups than in the AIS group. CT attenuation was significantly greater in the I-ADC group than in the AIS and MIA groups. In ROC curve analyses, the sensitivity and specificity of tumor size (cutoff, 11 mm) were 95.8% and 46.8%, respectively, and those for CT attenuation (cutoff, -680 HU) were 95.8% and 35.1%, respectively; the areas under the curve (AUC) were 0.75 and 0.77, respectively. A combination of tumor size and CT attenuation (cutoffs of 11 mm and -680 HU for tumor size and CT attenuation, respectively) yielded in a sensitivity and specificity of 91.7% and 71.4%, respectively, with an AUC of 0.82. CONCLUSIONS: Tumor size and CT attenuation were predictive factors of pathological invasiveness for pulmonary GGNs. Use of a combination of tumor size and CT attenuation facilitated more accurate prediction of invasive adenocarcinoma than the use of these factors independently.

Pulmonary artery reconstruction with a prosthetic conduit in lung cancer.

In radical pulmonary resection for advanced lung cancer, reconstruction of the pulmonary artery (PA) can preserve the lung parenchyma. Reconstruction techniques have gained acceptance because they enable the surgeon to avoid pneumonectomy. Various techniques have been documented, such as direct suturing, end-to-end anastomosis, and a patch or conduit reconstruction. We present two lobectomy cases in which the patients underwent PA reconstruction with prosthetic conduits because they were unfit for other procedures. In both cases, the conduits showed good postoperative patency. When interposition of a conduit is required for PA reconstruction, the use of a prosthetic conduit should be considered in selected cases.

Computed tomography attenuation predicts the growth of pure ground-glass nodules.

OBJECTIVES: Cases of lung cancer with pure ground-glass nodules (GGNs) have been detected with increasing frequency since the advent of computed tomography (CT), and growth is sometimes noted during follow-up. The objective of this study was to evaluate the potential predictive factors for pure GGN growth. MATERIALS AND METHODS: We retrospectively examined 124 cases involving pure GGNs. Patients were monitored for > 2 years using high-resolution CT. After a median follow-up period of 57.0 months, GGNs showed growth in 64 of the 124 cases. We compared the patient characteristics and tumor properties of cases with and without growth. The predictive value of the mean CT attenuation for GGN growth was evaluated using receiver operating characteristic curve analysis. RESULTS: Univariate analysis revealed significant differences between mean CT attenuation values in patients with and without growth (-602.9 ± 90.7 Hounsfield units [HU] vs -705.7 ± 77.7HU, P < 0.0001). The final incidence of growth was estimated to be significantly higher for lesions with a mean CT attenuation value of ≥ -670HU (n = 62; 93.2%) than for lesions with values of < -670HU (n = 62; 31.6%; P < 0.0001). The sensitivity and specificity for predicting tumor growth using this cutoff value were 78.1% and 80.0%, respectively (area under the curve, 0.81). CONCLUSION: The mean CT attenuation value could be useful in predicting the growth of GGNs.

Feasibility of using a vessel sealing system in a human pulmonary lobectomy: a retrospective comparison of this procedure with or without a vessel sealing system.

OBJECTIVE: Despite recent advances in video-assisted thoracoscopic lobectomy, some technical limitations still remain. Our current study purpose was to determine if the vessel sealing system (VSS) has utility in this procedure. METHOD: 112 patients who underwent an anatomic pulmonary lobectomy at our institute were evaluated retrospectively. The burst pressure of pulmonary vessels, which was divided into VSS (VSS group; n = 44) or manual ligature (ligature group; n = 53) groups, was measured experimentally in transected lungs. Perioperative clinical data was also retrospectively evaluated in patients treated with (VSS group) or without using VSS (n-VSS group). RESULTS: Burst pressures achieved adequate strength in both the VSS (600.0 ± 436.8 mmHg) and ligature (1057.4 ± 462.3 mmHg) groups. Compared with the n-VSS group, the VSS group patients showed lower intraoperative blood loss (115.4 ± 181.1 vs. 183.3 ± 159.1 ml), lower chest fluids by 3rd post-operative day (POD) (533.8 ± 264.8 vs. 705.3 ± 339.3 ml) and a shorter period of chest tube duration (4.1 ± 1.2 vs. 5.4 ± 2.4 days). No serious complications or perioperative (30 days) deaths occurred in either group. CONCLUSION: The VSS device has the advantage in pulmonary lobectomy procedures, especially those involving video-assisted thoracic surgery (VATS).

Changes in CT density of solitary capillary hemangioma of the lung upon varying patient position.

Solitary capillary hemangioma of the lung (SCHL) is a rare benign tumor that is difficult to differentiate from other nodular lesions, including lung cancer, on CT. We report a case of 58-year-old man with an SCHL of the left lower lung. A nodular lesion 7 mm in size varied in CT appearance when the position of the patient was changed: it was part solid and part ground-glass opacity (mixed GGO) in the supine position, but pure GGO (nonsolid) in the prone position. However, the possibility of a malignancy could not be completely excluded because the density of the lesion had increased slightly over the past five years, so the patient underwent surgical resection. The histological diagnosis was SCHL. Therefore, changes in the CT density of a nodule upon changing patient position may indicate an SCHL.

Experience with pulmonary resection for extensively drug-resistant tuberculosis.

Extensively drug-resistant tuberculosis is becoming a global threat. It is a relatively new phenomenon, and its optimal management remains undetermined. We report our experience in using pulmonary resection for treating patients with this disease. Records were reviewed of 54 consecutive patients undergoing a pulmonary resection for multidrug-resistant tuberculosis at Fukujuji Hospital between 2000 and 2006. These patients were identified using the definition approved by the World Health Organization Global Task Force on extensively drug-resistant tuberculosis in October 2006. Five (9%) patients (3 men and 2 women) aged 31-60 years met the definition. None of the patients was HIV-positive. Although the best available multidrug regimens were initiated, no patient could achieve sputum conversion. Adjuvant resectional surgery was considered because the patients had localized disease. Procedures performed included pneumonectomy (2) and upper lobectomy (3). There was no operative mortality or morbidity. All patients attained sputum-negative status after the operation, and they were maintained on multidrug regimens for 12-25 months postoperatively. All patients remained free from disease at the time of follow-up. Pulmonary resection under cover of state-of-the-art chemotherapy is safe and effective for patients with localized extensively drug-resistant tuberculosis.