Pleural and pulmonary metastases from nonseminomatous germ cell tumors successfully managed by extrapleural pneumonectomy.

INTRODUCTION: Surgery for postchemotherapy residual nonseminomatous germ cell tumors may be difficult due to exceptional lesion size and location. CASE PRESENTATION: A 47-year-old man presented with swelling and pain in the left scrotum. Computed tomography revealed a solid occupied lesion in the left scrotum with huge metastases in the left lung and pleura. Results of a left high inguinal orchiectomy indicated a pathological diagnosis of germ cell tumors of several histological types. The patient declined postoperative chemotherapy but returned to our department 10 months later with dyspnea. Serum tumor marker levels were restored to normal range by adjuvant chemotherapy. Thereafter, an extrapleural pneumonectomy was performed for the remaining tumors. He has since been asymptomatic without recurrence or dyspnea for over 5 years. CONCLUSION: Extrapleural pneumonectomy is a valid treatment option for the management of huge pleural and pulmonary metastases of nonseminomatous germ cell tumors.

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.

Thoracoscopic resection of a cystic seminoma of the mediastinum.

Mediastinal seminoma is an uncommon tumor that accounts for 25% of primary mediastinal germ cell tumors, which in turn comprise fewer than 5% of all germ cell tumors. Although CT normally shows a solid, lobulated tumor, mediastinal cystic seminoma has rarely been described. Here, we report a 24-year-old man who presented with a mediastinal cystic tumor that was resected after an 18-month delay via video-assisted thoracoscopic surgery while in the supine position; the procedure involved lifting the chest wall with a subcutaneous Kirschner wire. Pathological examination revealed a mediastinal cystic seminoma. No evidence of recurrence has been noted during 25 months of follow-up. Mediastinal cystic seminoma should be considered in the differential diagnosis of cystic lesions of the mediastinum. Moreover, video-assisted thoracoscopic resection may be an appropriate option for the diagnosis and treatment of such lesions.

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.

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.

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.

Video-Assisted Thoracic Surgery Thymectomy Versus Sternotomy Thymectomy in Patients With Thymoma.

BACKGROUND: This study was designed to evaluate the feasibility of video-assisted thoracoscopic surgery (VATS) and to compare the oncologic outcomes of VATS with those of sternotomy in patients with thymoma. METHODS: The clinical outcomes of 2,835 patients with thymic epithelial tumors treated between 1991 and 2010 in 32 Japanese institutions were collected retrospectively. The study compared postoperative complications, positive surgical margins, location of recurrence, and survival in 140 of 142 VATS-treated patients (VATS group) matched with 140 of 1,294 sternotomy-treated patients (ST group) by using propensity scores. RESULTS: Postoperative complications were observed in 8 patients in the VATS group. The morbidity rate in the VATS group was not different from that of the ST group (p = 0.25). Positive surgical margins were noted in 4 patients (3 in the VATS group; 1 in the ST group). There was no statistically significant difference in the recurrence rate between groups (median follow-up period: 3.7 years in the VATS group; 5.2 years in the ST group). In total the most frequent site of recurrence was pleural dissemination. In the VATS group, the 5-year recurrence-free survival rate was 93.8%, and the 5-year overall survival rate was 97.9%. There was no difference in the recurrence-free survival and overall survival rates between the VATS group and the ST group (p = 0.91 and p = 0.74, respectively). CONCLUSIONS: VATS thymectomy was feasible and comparable to sternotomy for the treatment of patients with thymoma with regard to morbidity, incomplete resection rate, and prognosis. However, additional follow-up is required to evaluate long-term outcomes.

Difficult Management of a Double-Lumen Endotracheal Tube and Difficult Ventilation during Robotic Thymectomy with Carbon Dioxide Insufflation.

Robotic surgery with carbon dioxide (CO2) insufflation to the thorax is frequently performed to gain a better operative field of view, although its intraoperative complications have not yet been discussed in detail. We treated two patients with difficult ventilation caused by distal migration of a double-lumen endotracheal tube (DLT) during robotic thymectomy. In the first case, migration of the DLT during one-lung ventilation (OLV) occurred after CO2 insufflation to the bilateral thoraxes was started. Oxygenation rapidly deteriorated because dependent lung expansion was restricted by CO2 insufflation. In the second case, migration of the DLT during OLV occurred while CO2 insufflation to a unilateral thorax and mediastinum was performed. In both cases, once migration of the DLT during OLV occurred with CO2 insufflation, readjusting the DLT became very difficult because our manipulation of bronchofiberscopy was prevented by the robot arms located above the patient's head and because deformation of the trachea/bronchus induced by CO2 insufflation caused a poor image of the bronchofiberscopic view. Thus, during robotic-assisted thoracoscopic surgery with CO2 insufflation, since there is a potential risk of difficult ventilation with a DLT and since readjustment of the DLT is very difficult, discontinuing CO2 insufflation and switching to double-lung ventilation are needed in such a situation.

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.

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.

Complete cervical tracheal transection due to blunt trauma.

Case: A 31-year-old man was caught up in the rotor of a snow-removing truck. He was diagnosed with tension pneumothorax and managed with tube thoracostomy in the ambulance. But he was left with respiratory discomfort. Computed tomography scan suggested the diagnosis of complete cervical tracheal transection. Outcome: The endotracheal tube was advanced distal to the transection site under bronchoscopic guidance, which stabilized the patient's cardiopulmonary condition. The tracheal injury healed well after emergent surgical repair. Conclusion: Complete cervical tracheal transection is rare and requires a high index of suspicion for timely diagnosis. It is important to secure the airway, which can be done by fiberoptic bronchoscopy.

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.

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.

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.

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.