[Surgical Case of the Primary Pulmonary Leiomyosarcoma:Report of a Case].

A 70-year-old man was referred for an abnormal chest shadow. Enhanced computed tomography (CT) revealed a well-circumscribed lung tumor of 53 mm in diameter in the left upper lobe with slight enhancement. Positron emission tomography-CT showed a high maximum standardized uptake value for the tumor but no metastasis in the lymph nodes or other organs. Although a definitive diagnosis could not be made by transbronchial biopsy, the tumor was highly suspected to be malignant based on the radiological findings, and a left upper lobectomy with mediastinal lymph nodes dissection was performed for definitive diagnosis and treatment. A pathological examination showed the tumor to be composed of mitotic spindle-shaped cells, which were positive for α-smooth muscle actin, desmin, and caldesmon. The MIB-1 labelling index was 60~70%. According to these pathologic findings, the tumor was identified as a leiomyosarcoma. Metastases to the skin of chest and hilar lymph nodes were noted six months after the surgery for which radiotherapy was performed.

[Metaplastic Thymoma Underwent Surgery:Report of a Case].

Metaplastic thymoma is a rare histologic variant of thymic epithelial tumors and is characterized by a biphasic growth pattern. We herein report the case of 44-year-old woman who underwent surgery for metaplastic thymoma. Computed tomography scan revealed a well-circumscribed mediastinal tumor: 56 mm in diameter with homogenous enhancement. The tumor was suspected to be a non-invasive thymoma, and thymomectomy with resection of the surrounding thymus was performed using thoracoscopy. The resected tumor measured 60 mm and was grossly well-encapsulated. The cut surface was gray to white and homogenous. Microscopically, the epithelial components took the form of an anastomosing nest to broad trabeculae intertwining with the bundle of spindle cells. Mitosis was not found and the Ki-67 index was < 1%. Cytokeratin 5/6 was strongly positive in the epithelial components composed of polygonal cells. Terminal deoxynucleotidyl transferase positive immature T cells were not observed. Based on these pathologic findings, the tumor was identified as metaplastic thymoma.

[The Outcome of Second Anatomical Pulmonary Resection for Ipsilateral Metachronous Lung Cancer].

INTRODUCTIONS: When the first intervention for lung cancer is anatomical resection, the ipsilateral repeat anatomical resection for metachronous second lung cancer becomes technically challenging. Herein, we report the outcomes of second anatomical pulmonary resection for ipsilateral metachronous lung cancer at our institution. SUBJECTS: Sixteen consecutive patients[ 10 men and 6 women, average age 70( range 59~81) years] were reviewed in this retrospective study. These patients underwent ipsilateral repeat anatomical resection for metachronous second lung cancer between 2009 and 2020. RESULTS: All case required right-sided lung resections. The previous interventions of patients included upper lobectomy, lower lobectomy, middle lobectomy, S2 segmentectomy, and S6 and S10a segmentectomy in 9, 4, 1, 1, and 1 case, respectively. The second surgical interventions were middle lobectomy, S6 segmentectomy, upper lobectomy, lower lobectomy, S1 segmentectomy, and S2 segmentectomy, in 6, 4, 2, 2, 1, and 1 case, respectively. Postoperative complications occurred in three patients. The median follow-up period was 53.5 months. Three patients died during the follow-up period. Of the 13 patients still alive, 6 had recurrence. The five-year overall survival rate was 80%. CONCLUSIONS: Although only a few cases were assessed, the prognosis after second anatomical pulmonary resection for ipsilateral metachronous lung cancer at our institution was satisfactory.

[Completion Pneumonectomy for the Recurrence of Lung Cancer].

INTRODUCTIONS: The morbidity and mortality after completion pneumonectomy (CP) are reportedly high. We, herein, report the outcomes of CP at our institution. SUBJECTS: Nine consecutive patients [7 men and 2 women, average age of 72 years(range 44~84 years)] who underwent CP for recurrence of lung cancer during 2012~2018 were retrospectively reviewed. RESULTS: Right-sided sleeve CP was performed in two cases and left-sided CP in seven cases. The indications for surgery were lymph node metastasis of the cancer, pulmonary metastasis, and bronchial stump recurrence in 4, 3, and 2 cases, respectively. Postoperative complications occurred in six patients. One of the patients who underwent right sleeve pneumonectomy developed bronchopleural fistula and died 68 days after the surgery. The mean follow-up period was 33 months, and four patients died during follow-up. Of the 5 patients still alive, 4 had no recurrence and 1 had recurrence in the stump of the main bronchus. The five-year overall survival rate was 78%. CONCLUSIONS: Although only few cases were assessed, the prognosis after CP at our institution was relatively good.

[Techniques and Outcomes of Segmentectomy for Non-small Cell Lung Cancer].

BACKGROUND: The most important step in lung segmentectomy is to determine an appropriate intersegmental plane to obtain sufficient pre- and intraoperative margins. Inappropriate dissection of the lung parenchyma leads to loss of oncological validity and additionally causes various complications such as pneumonia, prolonged air leakage, lung congestion, and atelectasis. OBJECTIVES: In this study, we evaluated the validity of segmentectomy for non-small cell lung cancer (NSCLC) based on evaluation of survival outcomes and recurrence patterns. OPERATIVE TECHNIQUE: In principle, we usually perform video-assisted thoracic surgery segmentectomy. Hilar dissection is performed along the intersegmental vein under ultrasonographic guidance, and the peripheral lung parenchyma is subsequently stapled. We usually create inflation-deflation lines from before to determine the intersegmental lines. Recently, near-infrared fluorescence imaging with indocyanine green is also used. METHODS: We retrospectively reviewed data of 101 patients who underwent segmentectomy for lung cancer between 2007 and 2014. RESULTS: The 5- and 10-year overall survival rates were 84% and 62%, respectively. The 5- and 10-year recurrence-free survival rates were 83% and 63%, respectively. Recurrence at the surgical margin occurred in 5 patients( pulmonary stump:4 patients, bronchial stump:1 patient). CONCLUSION: Segmentectomy may be acceptable for patients with Stage I NSCLC. Accurate determination of the intersegmental plane is essential to avoid stump recurrence.

[Diaphragmatic hernia complicated with diaphragmatic resection by automatic stapling device].

Nowadays, a diaphragmatic lesion is sometimes resected with use of an automatic stapling device, especially through video-assisted thoracoscopic procedure. We herein report 2 patients with a diaphragmatic hernia after diaphragmatic resection by automatic stapling devices. Etiology and cause of postoperative diaphragmatic hernia are discussed. Diaphragmatic resection by mechanical stapler was performed for thymic epithelial tumor recurring at the diaphragmatic pleura in both patients: 48-year-old man and 72-year-old woman. The former patient underwent a right diaphragmatic resection (3×4 cm in size) with a cartridge of mechanical stapler. Computed tomography (CT) and magnetic resonance imaging showed asymptomatic right diaphragmatic hernia 2 months after surgery. No symptom and progression occurred 8 years later. The latter patient underwent a right diaphragmatic resection (6×7 cm in size) with 2 cartridges of mechanical stapler. Diaphragmatic hernia advanced 7 months after surgery and required surgical intervention. Diaphragmatic repair was successful with the use of 8×6 cm expanded polytetrafluoroethylene patch. Surgical stump after diaphragmatic resection with automatic stapling device is easy to rupture during diaphragmatic movement synchronized with respiratory movement. Diaphragmatic resection with use of stapling device, which is a simple procedure, should be contraindicated.

Contralateral pneumothorax with postpneumonectomy syndrome: report of 18-year-old case.

We herein report a case of an 18-year-old male with left postpneumonectomy syndrome who underwent a bullectomy for right pneumothorax. The patient underwent a left pneumonectomy at the age of 1 year. At the age of 18 years, he developed right pneumothorax, and radiological findings revealed apical bullae in the right pleural cavity extending into the left atrophic thoracic cavity beyond the upper mediastinum. The right thoracoscopic bullectomy was successful. Modifications of selective lobar ventilation during surgery and thoracoscope position were described.

Diagnostic utility of trefoil factor families for the early detection of lung cancer and their correlation with tissue expression.

Trefoil factors (TFFs) are upregulated in numerous types of cancer, including those of the breast, the colon, the lung and the pancreas, suggesting their potential utility as biomarkers for screening. In the present study, the clinical relevance of serum or urinary TFFs as biomarkers were comprehensively evaluated and the correlation with TFF expression levels in lung cancer tissue was examined. Serum and urine were collected from 199 patients with lung cancer and 198 healthy individuals. Concentrations of serum and urinary TFF1, TFF2 and TFF3 were measured using ELISA and the potential of TFF levels to discriminate between cancer and non-cancer samples was evaluated. In 100 of the cancer cases, expression of TFF1-3 was analyzed using immunohistochemical staining of paraffin sections. Furthermore, the relationship between TFF levels and clinicopathological factors among these cancer cases was analyzed using immunohistochemistry of tissue specimens, quantified and statistically analyzed. While serum levels of all TFFs measured using ELISA were significantly higher in patients with lung cancer compared with those in healthy individuals, urinary TFFs were lower. Areas under the curve (AUC) of the receiver operating characteristic curves for serum/urinary TFF1, TFF2 and TFF3 were 0.709/0.594, 0.722/0.501 and 0.663/0.665, respectively. Furthermore, the combination of serum TFF1, TFF2, TFF3 and urinary TFF1 and TFF3 demonstrated the highest AUC (0.826). In the clinicopathological analysis, serum TFF1 was higher in the early pathological T-stage (pTis/1/2) compared with the later stage (pT3/4) and TFF2 was higher in the pN0/1 than the pN2 group. With regards to the histological types, urinary TFF1 was higher in squamous cell carcinoma than adenocarcinoma (AC), but TFF2 tended to be higher in AC. Using immunohistochemical analysis, although TFF1 and TFF3 expression showed positive correlation with serum concentrations, TFF2 was inversely correlated. In conclusion, serum and urinary TFF levels are promising predictive biomarkers, and their measurements provide a useful in vivo and non-invasive diagnostic screening tool. In particular, TFF1 and TFF3 could be surrogate markers of clinicopathological profiles of human lung cancer.

A case of prominent immunoglobulin G4-positive lymphadenopathy in response to microscopic lung cancer.

Immunoglobulin G4 (IgG4)-related disease is established as a new clinical entity, characterized by high levels of plasma IgG4 and IgG4-positive plasma cell infiltration. However, the elevation of plasma IgG4 and infiltration of IgG4-positive cells have been observed in other diseases, including malignancy. We experienced a case of prominent IgG4-positive lymphadenopathy, which was diagnosed as a reactive lesion in response to lung cancer. The cancerous lesion was so small in size that it was difficult to reveal the coexisting lung cancer. Surgical lymph node biopsy and endobronchial ultrasound-guided transbronchial needle aspiration did not reveal lymph node metastasis of cancer. Mediastinal lymph node dissection finally revealed it. After the right upper lobectomy, the patient underwent postoperative chemotherapy and remains cancer-free after 1 year. Our case suggests that close examination and careful follow-up are necessary when IgG4-positive lymphadenopathy is observed.

Salvage Surgery Post Definitive Chemoradiotherapy and Durvalumab for Lung Cancer.

Although concurrent chemoradiotherapy (CRT) followed by consolidation immunotherapy considerably improves the duration of survival in patients with unresectable stage III non-small cell lung cancer (NSCLC), few data are available on the management of local relapse after therapy. We present a patient with initially unresectable NSCLC who underwent a right upper lobectomy with reconstruction of the bronchus and pulmonary artery after definitive CRT, followed by consolidation durvalumab. No postoperative complications occurred, and he was recurrence-free at the 10-month follow-up. Salvage surgery might be a viable option for local relapse of NSCLC treated with definitive CRT and durvalumab.

Video-assisted thoracic surgery for a case of chronic progressive pulmonary aspergillosis undergoing haemodialysis complicated by anorexia nervosa: a case report.

We describe the case of a 37-year-old female with chronic progressive pulmonary aspergillosis (CPPA) with anorexia nervosa (AN) while undergoing haemodialysis for renal failure, who had video-assisted thoracic surgery (VATS) due to recurrent haemoptysis. She was referred to the Department of Respiratory Medicine for evaluation of an abnormal chest shadow. She was diagnosed with CPPA by serological examinations, radiological features, and bacterial culture. She was initially treated with oral antifungal therapy and transcatheter embolization. VATS lobectomy was eventually performed despite the AN and haemodialysis because of poorly controlled haemoptysis. The postoperative course was uneventful, and the final histopathological examination confirmed CPPA.

Diaphragmatic paraganglioma protruding into the right thoracic cavity.

Paragangliomas in the diaphragm are extremely rare. We report the case of a 27-year-old woman with a nonfunctioning paraganglioma protruding superiorly from the right diaphragm. The patient underwent an anterior thoracotomy, and a supradiaphragmatic tumor (70 mm in diameter), which compressed the inferior vena cava and the right hepatic vein, was completely resected by combined partial resection of the right diaphragm and pericardium. To our knowledge, this is the first report of a paraganglioma situated both on the diaphragm and close to the inferior vena cava and hepatic vein. KEY POINTS.

Can the Japanese National Clinical Database risk calculator predict long-term survival of patients who undergo palliative segmentectomy for primary lung cancer?

OBJECTIVES: Selection criteria for palliative limited surgery in patients with non-small cell lung cancer (NSCLC) can vary by institution or surgeon. We retrospectively reviewed outcomes of poor-risk patients who underwent palliative segmentectomy (PS), using the National Clinical Database Risk Calculator (RC). METHODS: We retrospectively analyzed medical records of patients with NSCLC tumors ≥ 20 mm and consolidation/tumor ratios ≥ 0.5 on computed tomography, who underwent PS from January 2009 to March 2016. Median follow-up time was 47 months (range 2-102 months). RESULTS: We enrolled 67 patients (median age: 73.0 years), of whom 54 received thoracoscopic surgery and 28 received medial lymph-node dissection. The RC's mean predictive probability rate for perioperative mortality or severe complications was 7.1%. Of the 67 patients, 24 patients (43.0%) suffered post-surgical complications, including 2 (3%) who died in hospital; 17 eventually suffered NSCLC recurrences and/or metastases, 11 eventually died from NSCLC, and 17 died from other diseases. Five-year overall survival (OS) was 59.4%. When the patients were divided into high-risk (HR) and low-risk (LR) groups based on the RC, 5-year OS was significantly less in the HR group (43.9%) than in the LR group (82.2%; P < 0.05). CONCLUSION: The RC, which was developed primarily to determine perioperative risk, can predict long-term prognosis for compromised patients who undergo PS.

TFF-1 Functions to Suppress Multiple Phenotypes Associated with Lung Cancer Progression.

INTRODUCTION: Trefoil Factor (TFF) is a member of a protein family comprised of three isoforms, of which TFF-1 exhibits antithetical functions; promotion or suppression of cell proliferation, survival and invasion, depending on the cancer type. However, the pathobiological function of TFF-1 in lung carcinoma has been still unclear. METHODS: We examined the expression and secretion of TFF-1 using cultured human lung carcinoma cells by immunoblotting, immunofluorescence, enzyme-linked immunosorbent assay and quantitative real-time PCR analyses. The effects of TFF-1 on various phenotypes were analyzed in two cell lines, including those transfected with cDNA encoding TFF-1. Cell proliferation and death were examined by hemocytometer cell counting and by colorimetric viability/cytotoxicity assay. Cell cycle profile, migration and invasion were also examined by flow cytometry, wound healing assay and Matrigel Transwell assay, respectively. The effect of TFF-1 overexpression was confirmed by additional transfection of TFF-1-specific siRNA. RESULTS: Endogenous TFF-1 protein expression and secretion into the media were observed exclusively in adenocarcinoma-derived cell lines. Forced overexpression of TFF-1 drove cell cycle transition, while the proliferation decreased by 19% to 25% due to increased cell death. This cell death was predominantly caused by apoptosis, as assessed by the activation of caspase 3/7. Cell migration was also suppressed by 71% to 82% in TFF-1-transfected cells. The suppressive effect of TFF-1 on proliferation and migration was restored by transfection of TFF-1 siRNA. Moreover, invasion was also suppressed to 77% to 83% in TFF-1-transfected cells. CONCLUSION: These findings reveal that TFF-1 functions as a suppressor of cancer proliferation by induction of apoptosis, cell migration and invasion and thus may provide a synergistic target for potential treatment strategies for human lung carcinoma.

The length of the left superior pulmonary vein stump after left upper lobectomy depends on its position to the left atrial appendage.

BACKGROUND: A longer left superior pulmonary vein (LSPV) stump may increase the risk for postoperative cerebral infarction. Although the residual stump is generally longer after left upper lobectomy (LUL) than for other lobectomies, the length of the LSPV stump after LUL may be influenced by the anatomical relationship between the left atrial appendage (LAA) and the LSPV. Our aim in this study was to investigate the influence of this anatomical relationship on the residual length of the LSPV stump after LUL. METHODS: This was a retrospective analysis of 85 patients who underwent LUL at our institution, between January 2014 and March 2018. Based on pre-operative computed tomography (CT) images, the anatomical relationship between the LSPV and the LAA was classified into two patterns, namely an antero-superior and a postero-inferior pattern. The length of the LSPV stump for these two patterns was evaluated on postoperative CT images and compared between the two groups. RESULTS: Of the 85 patients, 49 were classified in the antero-superior pattern and 36 in the postero-inferior pattern. The mean length of the LSPV stump after LUL, overall, was 21.9 (range, 15-38) mm, with the stump being significantly longer for the antero-posterior (24.2 mm) than postero-inferior (18.9 mm) pattern. CONCLUSIONS: The anatomical relationship between the LSPV and LAA, identified on pre-operative CT images, was associated with the length of the LSPV stump after LUL.

Pericardial fat pad plombage for pulmonary cavity causing massive air leakage.

BACKGROUND: Secondary pneumothorax after chemotherapy for a malignant pulmonary tumor is a complication from a large cavity causing refractory pneumothorax. CASE PRESENTATION: A 61-year-old man was referred due to prolonged air leakage from a pulmonary cavity that developed after treatment for pulmonary metastases from renal cell carcinoma. As air leakage continued after thoracic drainage and endobronchial occlusion, we planned thoracoscopy-assisted surgery. Intraoperatively, a large cavity opening to the pulmonary cavity was found in the left upper lobe. As it was difficult to repair the fistula using staplers or direct sutures because the pleura around the cavity was thick and hard, we attempted to plombage the cavity with a pericardial fat pad. After the operation, air leakage immediately disappeared and no recurrence of the pneumothorax was found. CONCLUSION: This novel method can be useful to seal a large bronchopleural fistula that causes refractory pneumothorax.

EphA2, a possible target of miR-200a, functions through the AKT2 pathway in human lung carcinoma.

We previously reported that miR-200a was highly up-regulated in lung carcinoma, exhibiting a copy number increase (CNI) of the AKT2 gene (AKT2+ group) in defined subsets, i.e., adenocarcinoma and early stages of carcinoma (pStage I/II). In this study, we searched possible targets of miR-200a in these subsets by IHC analyses focusing on the expression of known target proteins of miR-200a: beta-catenin, EphA2, ZEB1, PTEN, and YAP-1, as well as E-cadherin, the expression of which is suppressed by ZEB1. Among those 6 proteins, when all 38 cases of surgically resected specimens were analyzed as a whole, IHC score of ZEB1 was inversely (ρ=-.417) and E-cadherin was positively (ρ=.345) correlated with miR-200a expression. However, only EphA2 was inversely correlated with the expression of miR-200a in adenocarcinoma (ρ=-.496) and in pStage I/II group (ρ=-.547), while no correlation was seen in non-adenocarcinoma, squamous cell carcinoma, or pStage III carcinoma. Furthermore, by comparison of 3 groups categorized according to the AKT gene increase, only EphA2 was down-regulated to a statistically significant level in the AKT2+ group in both adenocarcinoma (p=.0447) and pStage I/II carcinoma (p=.0458). These results suggest that in lung carcinomas, higher Akt activation caused by increased AKT2 gene copy number leads to the upregulation of miR-200a, which exerts its function as a suppressor of EphA2 in adenocarcinoma and the early stages of carcinomas.

Massive lymphatic leakage after lung cancer surgery via median sternotomy.

We report a case of intractable chylothorax after right upper lobectomy and nodal dissection via median sternotomy for lung cancer in a 67-year-old man. Lymphangiography (LAG) with lipiodol and sequential computed tomography showed the thoracic duct in the left posterior mediastinum and massive lymphatic leakage in the anterior and middle mediastinum. The Chylous leakage was resolved by LAG with lipiodol. Our findings suggest that variation of the thoracic duct should be evaluated by LAG when intractable chylothorax or chylomediastinum develops after anterior mediastinal surgery.

Screening of the copy number increase of AKT in lung carcinoma by custom-designed MLPA.

Treatments for lung cancer include therapies targeting aberrant oncoproteins, but there remains a high medical need for novel therapies. Our previous studies showed that gene amplification/high-level polysomy of AKT1/2 occurs in more than 10% of lung carcinomas. Here, we describe multiplex ligation-dependent probe amplification analysis (MLPA) as a high-throughput method to evaluate copy number increases (CNIs) of AKT1/2 in lung carcinomas. The performance of MLPA using custom-made probes in formalin-fixed paraffin-embedded tissue was evaluated by comparing it to immunohistochemistry and fluorescence in situ hybridization analysis (FISH). By MLPA, we found 4 out of 30 samples harboring gene "gain" when the conventional cutoff value (> 1.3) was used. Two samples with gene amplification by FISH had MLPA values of 1.85 and 1.75, which were lower than the conventional cutoff for "amplification" (> 2.0). Moreover, samples with CNIs due to polysomy by FISH gave MLPA values between 1.13 and 1.47, so some samples had lower values than 1.3. The reasons appeared to be stromal contamination and the presence of carcinoma cells without CNIs. However, when we changed the cutoff for "gain" to the "average+2xstandard error", we detected CNIs in 10 samples, with only one each of false-positive and false-negative results. The sensitivity was 90% and the specificity was 98%. Consistently, all cases exhibiting CNI by this criteria revealed Akt activation. In conclusion, MLPA implemented with custom-made probes and an optimized cutoff value is a feasible screening method to semi-quantitatively detect oncogene aberrations, and may contribute to the design of individualized, molecularly targeted therapies against lung carcinoma.