[Case of Testicular Seminoma in Which the Diagnosis Was Preceded by the Discovery of Atypically Shaped Metastatic Nodules in the Lung].

A 57-year-old man visited our hospital due to abnormal chest X-ray findings. Chest computed tomography(CT)showed amalgamated beaded solid nodules in the right upper lobe of the lung. Lobectomy of the right upper lobe was performed and the nodule was histologically determined to be seminoma. Positron emission tomography(PET)-CT showed high 18F-fluorodeoxyglucose(FDG)uptake in the lung nodules and faint uptake in the left testicle. As ultrasound and palpation detected no tumor in the testes, consent to perform orchiectomy was not obtained. Considering the PET-CT findings, we diagnosed testicular seminoma with solitary pulmonary metastasis, which is extremely rare.

[A Case of Hypopharyngeal Cancer Discovered after Recurrent Aspiration Pneumonia].

CASE: A 69-year-old man reported globus sensations since November X and was diagnosed with bilateral pneumonia in December at a local clinic. The patient was subsequently admitted to our hospital for a diagnosis and treatment. His pneumonia improved with antibiotics, but pneumonia recurred. However, pneumonia recurred in February X+1, and antibiotic treatment once again provided relief. However, globus sensations persisted even after the remission of pneumonia. Endoscopic observations revealed a tumor in the hypopharynx, which caused saliva aspiration into the insufficiently closed vocal cords. The hypopharyngeal cancer was treated with chemoradiotherapy, and thereafter, the frequency of aspiration pneumonia decreased. CONCLUSION: The present case illustrated that sometimes aspiration pneumonia may be caused by laryngeal and hypopharyngeal cancer.

[A Case of Advanced Squamous Cell Carcinoma of the Lung 19 Years after Chemoradiotherapy of Limited-Disease Small-Cell Lung Cancer].

A 65-year-old man was referred to our hospital because of a fever and cough 19 years after chemoradiotherapy for small-cell lung cancer(SCLC)in the right middle lobe. Computed tomography(CT)revealed a normal right middle lobe, but found pneumonia and a tumor at the bronchial entrance of the right upper lobe. After treating the pneumonia with antibiotics and prednisolone, transbronchial biopsies(TBBs)revealed the tumor to be squamous cell carcinoma(SCC). Eight lines of chemotherapy including immune checkpoint inhibitors(ICIs)were completed with a 42-month survival following the initiation of chemotherapy for SCC, after which he ultimately died of hemoptysis. Survival of over 10 years from small- cell cancer is rare. We herein report the prognosis of SCLC and the treatment of subsequent primary lung cancer.

The Interstitial Lung Disease-Gender-Age-Physiology Index Can Predict the Prognosis in Surgically Resected Patients with Interstitial Lung Disease and Concomitant Lung Cancer.

BACKGROUND: The interstitial lung disease-gender-age-physiology (ILD-GAP) index and staging system have been reported as a clinical prognostic factor for ILD, including all ILD subtypes. OBJECTIVES: The purpose of this study was to clarify the association of various prognostic indices, including the ILD-GAP index, with the prognosis, the incidence of acute exacerbations of ILD (ILD-AE), and the use of long-term oxygen therapy (LTOT) after surgery in surgically resected patients with ILD and concomitant lung cancer, to provide additional information when considering whether it is safe to perform surgery. METHODS: The medical records of patients with ILD and concomitant lung cancer who had undergone surgery at Shinshu University Hospital between August 2001 and September 2016 were retrospectively analyzed. RESULTS: There were significant differences in survival between the ILD-GAP index: 0-1 and ≥4 groups (p = 0.0001) and between the ILD-GAP index: 2-3 and ≥4 groups (p = 0.0236). A higher ILD-GAP index was independently associated with the risk of death (hazard ratio [HR] 1.32030; p = 0.0059). A higher body mass index (BMI) and a higher serum C-reactive protein (CRP) level were independently associated with the incidence of ILD-AE (HR 1.28336; p = 0.0206 and HR 26.3943; p = 0.0165, respectively). A higher severity of ILD on chest high-resolution computed tomography (HRCT) was independently associated with the use of LTOT (HR 2.78670; p = 0.0313). CONCLUSIONS: The ILD-GAP index can predict the prognosis in surgically resected patients with ILD and concomitant lung cancer. The BMI and serum CRP levels were independent determinants that predicted the incidence of ILD-AE. The severity of ILD on chest HRCT was an independent determinant that predicted the use of LTOT.

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.

[Significance of Thoraco-laparoscopic Observation in Repairing Diaphragmatic Injury by the Penetrating Trauma].

A 53-year-old man with a penetrating trauma was admitted to our hospital. Thoracoabdominal computed tomography (CT) on admission showed left diaphragmatic injury and peritoneal fat in the left thoracic cavity. Under a diagnosis of the traumatic diaphragmatic injury, an emergency operation was performed, and the left diaphragm was repaired. No other injuries were found in the thoracic and abdominal organs by thoraco-laparoscopic observation. The postoperative course was uneventful, and the patient left hospital on the 14th day after surgery. In case of the diaphragm injury, it is important to confirm the probable injuries of other organs by thoraco-laparoscopic observation.

The Preoperative Composite Physiologic Index May Predict Mortality in Lung Cancer Patients with Combined Pulmonary Fibrosis and Emphysema.

BACKGROUND: It remains unclear whether the preoperative pulmonary function parameters and prognostic indices that are indicative of nutritional and immunological status are associated with prognosis in lung cancer patients with combined pulmonary fibrosis and emphysema (CPFE) who have undergone surgery. OBJECTIVE: The aim of this study is to identify prognostic determinants in these patients. METHODS: The medical records of all patients with lung cancer associated with CPFE who had undergone surgery at Shinshu University Hospital were retrospectively reviewed to obtain clinical data, including the results of preoperative pulmonary function tests and laboratory examinations, chest high-resolution computed tomography (HRCT), and survival. RESULTS: Univariate Cox proportional hazards regression analysis showed that a high pathological stage of the lung cancer, a higher preoperative serum carcinoembryonic antigen level, and a higher preoperative composite physiologic index (CPI) were associated with a high risk of death. Multivariate analysis showed that a high pathological stage of the lung cancer (HR: 1.579; p = 0.0305) and a higher preoperative CPI (HR: 1.034; p = 0.0174) were independently associated with a high risk of death. In contrast, the severity of fibrosis or emphysema on chest HRCT, the individual pulmonary function parameters, the prognostic nutritional index, the neutrophil-to-lymphocyte ratio, and the platelet-to-lymphocyte ratio were not associated with prognosis. In the Kaplan-Meier analysis, the log-rank test showed significant differences in survival between the high-CPI and the low-CPI group (p = 0.0234). CONCLUSION: The preoperative CPI may predict mortality and provide more powerful prognostic information than individual pulmonary function parameters in lung cancer patients with CPFE who have undergone surgery.

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 Outcomes of a Limited Resection for Non-Small Cell Lung Cancer Based on Differences in Pathology.

OBJECTIVE: A precise preoperative diagnosis of in situ or minimally invasive carcinoma may identify patients who can be treated by limited resection. Although some clinical trials of limited resection for lung cancer have started, it will take a long time before the results will be published. We have already reported a large-scale study of limited resection. We herein report the data for a subclass analysis according to differences in pathology. METHODS: Data from multiple institutions were collected on 1710 patients who had undergone limited resection (segmentectomy or wedge resection) for cT1N0M0 non-small cell carcinoma. The disease-free survival (DFS) and recurrence-free proportion (RFP) were analyzed. Small cell carcinomas and carcinoid tumors were excluded from this analysis. Adenocarcinomas were sub-classified into four groups using two factors, the ratio of consolidation to the tumor diameter (C/T) and the tumor diameter alone. RESULTS: The median patient age was 64 (20-75) years old. The mean maximal diameter of the tumors was 1.5 ± 0.5 cm. The DFS and RFP at 5 years based on the pathology were 92.2 and 94.7 % in adenocarcinoma (n = 1575), 76.3 and 82.4 % in squamous cell carcinoma (SqCC) (n = 100), and 73.6 and 75.9 % in patients with other tumors (n = 35). The prognosis of adenocarcinoma in both groups A (C/T ≤0.25 and tumor diameter ≤2.0 cm) and B (C/T ≤0.25 and tumor diameter >2.0 cm) was good. In SqCC, only segmentectomy was a favorable prognostic factor. In the groups with other pathologies, large cell carcinomas were worse in prognosis (the both DFS and RFP: 46.3 %). CONCLUSION: Knowing the pathological diagnosis is important to determine the indications for limited resection. Measurement of the tumor diameter and C/T was useful to determine the indications for limited resection for adenocarcinoma. Limited resection for adenocarcinomas is similar with a larger resection, while the technique should be performed with caution in squamous cell carcinoma and other pathologies.

Left ventricular stroke volume decreases due to surgical procedures of anatomical lung resection.

OBJECTIVES: The influence of lung resection on cardiac function has been reported, and previous studies have mainly focused on right ventricular (RV) dysfunction. As few studies have analyzed changes in left ventricular hemodynamic variables caused by lung resection, we aimed to investigate the perioperative changes in left ventricular stroke volume (LVSV) caused by anatomical lung resection. METHODS: We enrolled 61 patients who underwent anatomical lung resection and perioperative LVSV monitoring. The Flo Trac system was used for dynamic monitoring. We investigated changes in LVSV after lung resection and the factors that affected these changes. The operative procedures that contributed to these changes were also investigated. RESULTS: LVSV decreased after anatomical lung resection in the majority of patients (n = 38, 62.2%). Operative procedures affecting this change were (a) taping the superior pulmonary vein (SPV; right: V1-3) before dorsal part procedure (e.g., major fissure division of right upper lobectomy, A1 + 2c, and A4 + 5 division of left upper lobectomy); (b) division of the SPV (right: V1-3, V4 + 5); (c) division of A6-10 (in lower lobectomy); and (d) finish division of all vessels. CONCLUSIONS: LVSV decrease was caused by anatomical lung resection in the majority of patients owing to the intraoperative procedures described above.

Extremely Large Fluid Collection in the Superior Aortic Recess Misdiagnosed as Mediastinal Tumors: A Report of Two Cases.

The superior aortic recess is one of the superior portions of the transverse sinus which is located around the ascending aorta. The fluid collection of the superior aortic recess is sometimes revealed on chest computed tomography, and it becomes more difficult to differentiate from a cystic tumor or lymphadenopathy when the amount of collected fluid is large or the fluid is extended into another area. We report two cases of fluid collection in the superior aortic recess which was misdiagnosed as a cystic mediastinal tumor that underwent surgical resection. An extremely large amount of fluid collection and cephalad extension led us to this clinical course.

A very rare case of spontaneous regression of basaloid squamous cell carcinoma of the lung.

Spontaneous regression of non-small cell lung cancer is relatively rare. Here, we present a very rare case of spontaneous regression of lung cancer which occurred in a patient with basaloid squamous cell lung cancer. To the best of our knowledge, this is the first report of such a case. A 76-year old man was referred to our hospital with nodules in the right upper lobe determined by chest computed tomography. The nodules spontaneously regressed during follow-up. Two years later, the tumor had regrown and the patient subsequently underwent surgery. The pathological findings showed basaloid squamous cell carcinoma. Stimulation of the immune system was considered to be the cause of the spontaneous regression and CD-8 positive and CD-4 positive lymphocytes might play an important role.

Surgical outcomes in patients with small cell lung cancer: comparative analysis of computed tomograpy-detected patients with others.

BACKGROUND: It is shown that low-dose computed tomography (CT) screening is useful for a reduction in lung-cancer-specific mortality in heavy smokers. However, the information about effectiveness according to the histological types of lung cancer has not been adequately investigated especially small cell lung cancer (SCLC). The present study was performed to see the clinical benefit of CT screening in patients with SCLC following thoracotomy. METHODS: We retrospectively reviewed the outcome in patients with early stage SCLC who initially underwent thoracotomy. The clinical stages and actuarial survival were estimated according to the three means of detection of SCLC: chest CT, radiographic screen, and symptomatically prompted cases. RESULTS: Sixty-nine patients (men/women, 63/6; mean age, 70 years) with SCLC underwent thoracotomy between 1991 and 2010 including chest CT (n = 13), radiographic screening (n = 39), and symptomatically prompted cases (n = 17). Pathological staging information included stage IA (n = 25), IB (n = 8), IIA (n = 13), IIB (n = 5), IIIA (n = 11), and IIIB (n = 7). Median survival time was 30.0 (95% confidence interval (CI): 22.0 to 57.0) months, with overall survival at 5 years of 34.3% (95% CI, 23.47 to 47.3). Nine patients (69%) with stage I were detected by CT which was significantly higher than those in other detection arms. However, there were no significant differences in the survival between CT and other detection arms. CONCLUSIONS: CT examination may be useful for detection in early stage SCLC potentially suitable for surgery, but the contribution to better clinical outcome in patients with SCLC remains unclear.

[Delayed hemothorax due to blunt chest trauma].

We report 2 cases of delayed hemothorax due to blunt chest trauma. A 48-year-old man who fell down and got a blow at the right chest had a checkup with a 1st aid outpatient. By the X-rays at the time of the 1st examination, the hemothorax was not noted. The next day, He has been transported to our hospital for atypical absence. Hemothorax was suggested by computed tomography (CT) and chest drainage was enforced. A 79-year-old man got a blow at the anterior chest by traffic accident and had a checkup in the 1st hospital. The abnormality was not recognized in the chest CT at that time. For the left hemiparesis, he was transported to our hospital the next day. Hemothorax was suggested by CT and chest drainage was enforced.

Sjögren syndrome-related plasma cell disorder and multifocal nodular AL amyloidosis: clinical picture and pathological findings.

Background: Localized nodular deposits of AL amyloid are seen in different tissues/organs; however, the pathogenesis of this form of amyloidosis remains unclear. Recently, Sjögren syndrome combined with localized nodular AL amyloidosis has been noted. Here, we report Sjögren syndrome cases showing multifocal nodular AL amyloidosis and the followed benign course. Materials and methods: We investigated the clinical pictures and histopathological findings of three cases with both presence of Sjögren syndrome and localized nodular AL amyloidosis, paying a special attention to the distribution of amyloidoma. Results: All three cases were middle-aged females. In two of three cases localized deposits of AL amyloid preceded Sjögren syndrome. Amyloidoma was detected in scalp, eyelid, cheek, larynx, trachea, lung and breast, and around these amyloid-deposited lesions infiltration of plasma cells was seen. Pulmonary amyloidosis was consistently accompanied with parenchymal cystic lesions, but this amyloidosis did not produce any significant respiratory symptoms. Some of large pulmonary amyloidomas showed cavity formation and subsequent shrinkage. In two cases amyloid deposition was found on gastric mucosa. Two cases received small doses of oral prednisone, with no further appearance of amyloidoma. Conclusion: Sjögren syndrome-related plasma cell disorder may be responsible for the formation of this unique multifocal nodular AL amyloidosis.

Multiple primary chordomas of the lung.

We here report the case of a 40-year-old man with primary pulmonary chordomas. Although an abnormality had been noted on a chest radiograph at age 26 years, the patient had not undergone further examination at that time because he was asymptomatic. Standard chest radiographs and computed tomography showed slow-growing, multiple bilateral pulmonary nodules. Two tumors were resected thoracoscopically to obtain a diagnosis. Pathologic examination resulted in a diagnosis of chordomas. Subsequent systemic examination revealed no additional lesions, not even in the axial skeleton. The patient is alive without any new lesions 38 months after surgery. These clinical and pathological findings suggest that our patient has multiple primary chordomas of the lung, which is an extremely rare condition.

Utility of bronchial lavage fluids for epithelial growth factor receptor mutation assay in lung cancer patients: Comparison between cell pellets, cell blocks and matching tissue specimens.

The detection of epidermal growth factor receptor (EGFR) mutations is necessary for the selection of suitable patients with non-small cell lung cancer (NSCLC) for treatment with EGFR tyrosine kinase inhibitors. Cytology specimens are known to be suitable for EGFR mutation detection, although tissue specimens should be prioritized; however, there are limited studies that examine the utility of bronchial lavage fluid (BLF) in mutation detection. The purpose of the present study was to investigate the utility of BLF specimens for the detection of EGFR mutations using a conventional quantitative EGFR polymerase chain reaction (PCR) assay. Initially, quantification cycle (Cq) values of cell pellets, cell-free supernatants and cell blocks obtained from three series of 1% EGFR mutation-positive lung cancer cell line samples were compared for mutation detection. In addition, PCR analysis of BLF specimens obtained from 77 consecutive NSCLC patients, detecting EGFR mutations was validated, and these results were compared with those for the corresponding formalin-fixed paraffin-embedded (FFPE) tissue specimens obtained by surgical resection or biopsy of 49 of these patients. The Cq values for mutation detection were significantly lower in the cell pellet group (average, 29.58) compared with the other groups, followed by those in cell-free supernatants (average, 34.15) and in cell blocks (average, 37.12) for all three series (P<0.05). Mutational status was successfully analyzed in 77 BLF specimens, and the results obtained were concordant with those of the 49 matching FFPE tissue specimens. Notably, EGFR mutations were even detected in 10 cytological specimens that contained insufficient tumor cells. EGFR mutation testing with BLF specimens is therefore a useful and reliable method, particularly when sufficient cancer cells are not obtained.

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.

A novel, rapid point-of-care test for lung cancer patients to detect epidermal growth factor receptor gene mutations by using real-time droplet-PCR and fresh liquid cytology specimens.

Epidermal growth factor receptor gene (EGFR) mutations are associated with response to tyrosine kinase inhibitors (TKIs) in patients with non-small cell lung cancer (NSCLC). We developed a novel, rapid EGFR mutation assay using a real-time droplet-polymerase chain reaction machine (EGFR d-PCR assay). The purpose of this study was to validate the performance of the EGFR d-PCR assay using fresh liquid cytology specimens. We analyzed three major EGFR mutations (L858R in exon 21, E746_A750del in exon 19 and T790M in exon 20) in 80 fresh liquid cytology specimens of adenocarcinoma (ADC) or NSCLC-not otherwise specified (NOS) via the EGFR d-PCR assay and conventional real-time PCR assay using the therascreen® EGFR RGQ PCR kit (Therascreen assay). In addition, we performed sensitivity assays using cell lines with EGFR mutations. The EGFR d-PCR assay detected 16 L858Rs, 8 E746_A750dels and 1 T790M mutation and the Therascreen assay detected 16 L858Rs, 11 deletions in exon 19 and 1 T790M mutation. The results were concordant between the two assays. The reaction time of the EGFR d-PCR assay was 8 min and 10 sec, but that of the Therascreen assay was 1 h and 45 min. Sensitivity, as assessed by the detection limit of the EGFR d-PCR assay was 0.5, 0.05 and 0.5% for L858R, E746_A750del and T790M, respectively. The EGFR d-PCR assay markedly reduced the detection time of major EGFR mutations with high sensitivity compared with the conventional Therascreen assay and is expected to expedite EGFR-TKI therapy for lung cancer patients, especially those in advanced stages.

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.