[Retrograde S(9+)10 Segmentectomy without Interlobar Fissurelectomy].

BACKGROUNDS: With increase of patients with a small-sized lung cancer, there is an increasing need for minimally invasive lung segmentectomy that can preserve respiratory function. We perform S(9+)10 segmentectomy with retrograde dissection of the pulmonary vein, bronchus, pulmonary artery, in order, without interlober fissurelectomy and staple dissection of the peripheral lung parenchyma. METHODS: Seven patients who underwent retrograde S(9+)10 segmentectomy between June, 2021 and May, 2022 in our hospital were retrospectively reviewed. RESULTS: No patient was converted to the open thoracotomy, without any complications including prolonged air leakage. The average operation time was 171 minutes( range 125 to 221), amount of bleeding was 25 ml( range 0 to 75). Median duration of chest tube insertion was 4 days( range 3 to 6), length of stay after surgery was 6 days (range 5 to 9). Pathologic stage showed pT1mi in 3 patients, pT1a in 3 patients, pT2a in 1 patient. No local recurrence was seen at this time. CONCLUSIONS: Retrograde S(9+)10 segmentectomy is feasible and facilitates interlobar procedure at the time of repeated segmentectomy or completion lobectomy.

[Thoracoscopic Surgery for Lung Cancer Invading the Superior Chest Wall].

We herein report a case of a 73-year-old man with lung cancer who underwent thoracoscopic right upper lobectomy with combined resection of the superior chest wall. His tumor was 48 mm in diameter and located in the posterior right lung apex involving the chest wall between ribs 1 and 3. The anterior aspects of the ribs 2 and 3 were separated using forceps under thoracoscopic vision. The first rib could be released from the tumor by peeling off the parietal pleura. An 8 cm incision was made posteriorly between the scapula and vertebrae to obtain the posterior aspect of the ribs 2 and 3. After separating the pulmonary vessels and bronchus, en bloc resection of the superior sulcus tumor was completed. Thoracoscopic chest wall resection of the superior sulcus tumor can be an alternative to the Paulson posterolateral-paravertebral thoracotomy approach, which can cause severe postoperative pain and limited range of motion of the shoulder joint.

[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.

Surgical resection for persistent localized pulmonary fungal infection prior to allogeneic hematopoietic stem cell transplantation: Analysis of six cases.

OBJECTIVE: Although invasive fungal disease (IFD) is an important complication in allogeneic hematopoietic stem cell transplantation (HSCT), the clinical significance of surgery, including the role of surgical resection for persistent pulmonary fungal disease prior to allogeneic HSCT in the current era with a variety of available antifungal agents, is controversial. We investigated the role of surgical resection. METHODS: We retrospectively investigated six patients who underwent surgical resection of suspected pulmonary fungal disease prior to allogeneic HSCT between April 2007 and June 2016 at our medical center. RESULTS: We present six patients who underwent surgical resection of suspected pulmonary fungal disease prior to allogeneic HSCT. In our case series, three of four patients who were given a presurgical diagnosis of possible IFD were given a proven diagnosis after surgery, including two cases of invasive aspergillosis (IA) and one case of mucormycosis. All surgeries were performed by video-assisted thoracic surgery (VATS) for lobectomy without major complications. Recurrence of IFD was not observed after allogeneic HSCT in any of the six patients. CONCLUSION: Our experience indicated that surgical resection of persistent localized pulmonary lesions of IFD before allogeneic HSCT was helpful for obtaining a definitive diagnosis and might be useful for reducing recurrence after HSCT.

Pulmonary mucoepidermoid carcinoma arising in a patient with Kartagener syndrome.

BACKGROUND: Kartagener syndrome, an autosomal recessive disorder with a triad of chronic sinusitis, bronchiectasis, and situs inversus, is characterized by recurrent respiratory tract infections and chronic inflammation of the lung. Information on comorbidities other than infections in patients with Kartagener syndrome is currently limited. CASE PRESENTATION: A 39-year-old, non-smoking female was diagnosed with Kartagener syndrome and admitted to Saitama Medical Center, Jichi Medical University, Japan. Computed tomography revealed an endobronchial massive shadow at the ostial site of the right upper lobe bronchus with atelectasis of the right upper lobe. The mass was surgically resected and pathologically diagnosed as mucoepidermoid carcinoma. The lesion had no vascular invasions and no metastases to the lungs or lymph nodes. The surgical margin was negative for carcinoma. Following surgery, the patient has been in good condition. CONCLUSIONS: The present case showed different clinicopathological characteristics from those previously reported in cases of Kartagener syndrome complicated by carcinoma. To the best of our knowledge, this is the first reported case of a young, non-smoking female with comorbid Kartagener syndrome and pulmonary mucoepidermoid carcinoma. This case report may provide a new perspective on the complications of Kartagener syndrome.

[Desmoid Tumor Treated by Wide Resection of the Anterior Chest Wall].

Desmoid tumors are rare mesenchymal proliferative tumors that are highly invasive but lack metastatic potential. We report the case of a 72-year-old man with a desmoid tumor arising from the anterior chest wall which invaded neighboring organs extensively. The patient complained of dyspnea on exertion and appetite loss and was referred to our hospital. Chest computed tomography revealed an anterior chest wall tumor 12 cm in diameter adjacent to the right lung, diaphragm, and sternum. An ultrasound-guided biopsy was conducted, and the tumor was diagnosed as a desmoid tumor. He underwent right-sided anterior chest wall resection with combined resection of the right lung, diaphragm, and sternum body. The chest wall defect was reconstructed using an expanded polytetrafluorethylene mesh (dualmesh). Although initial active surveillance has recently been recommended for asymptomatic patients with non-progressing desmoid tumors, our patient underwent resection because of his symptoms.

[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.

Loss of YAP1 defines neuroendocrine differentiation of lung tumors.

YAP1, the main Hippo pathway effector, is a potent oncogene and is overexpressed in non-small-cell lung cancer (NSCLC); however, the YAP1 expression pattern in small-cell lung cancer (SCLC) has not yet been elucidated in detail. We report that the loss of YAP1 is a special feature of high-grade neuroendocrine lung tumors. A hierarchical cluster analysis of 15 high-grade neuroendocrine tumor cell lines containing 14 SCLC cell lines that depended on the genes of Hippo pathway molecules and neuroendocrine markers clearly classified these lines into two groups: the YAP1-negative and neuroendocrine marker-positive group (n = 11), and the YAP1-positive and neuroendocrine marker-negative group (n = 4). Among the 41 NSCLC cell lines examined, the loss of YAP1 was only observed in one cell line showing the strong expression of neuroendocrine markers. Immunostaining for YAP1, using the sections of 189 NSCLC, 41 SCLC, and 30 large cell neuroendocrine carcinoma (LCNEC) cases, revealed that the loss of YAP1 was common in SCLC (40/41, 98%) and LCNEC (18/30, 60%), but was rare in NSCLC (6/189, 3%). Among the SCLC and LCNEC cases tested, the loss of YAP1 correlated with the expression of neuroendocrine markers, and a survival analysis revealed that YAP1-negative cases were more chemosensitive than YAP1-positive cases. Chemosensitivity test for cisplatin using YAP1-positive/YAP1-negative SCLC cell lines also showed compatible results. YAP1-sh-mediated knockdown induced the neuroendocrine marker RAB3a, which suggested the possible involvement of YAP1 in the regulation of neuroendocrine differentiation. Thus, we showed that the loss of YAP1 has potential as a clinical marker for predicting neuroendocrine features and chemosensitivity.

[Complete Video-assisted Thoracic Surgery for Lung Cancer].

Video-assisted thoracic surgery(VATS) lobectomy is currently accepted as an appropriate minimally invasive procedure for selected patients with early-stage non-small cell lung cancer(NSCLC). Complete VATS is defined as an operation in which no rib spreader is used and visualization is only through the video monitor, and not through the incisions. We perform complete VATS lobectomy via 5 ports since the assistant surgeon can use 2 instruments to provide a good operative field. Our indication for complete VATS lobectomy is not limited to early-stage NSCLC but also includes N1-2 disease. The overall 5-year survival rate in patients with N2 disease was 59% and the recurrence-free 5-year survival rate was 34% during a median follow-up of 54 months. In some experienced institutions, the indications for VATS in NSCLC are now expanding to various complex procedures such as pneumonectomy, sleeve lobectomy, en bloc chest wall resection, and reconstruction of the pulmonary artery. Except for simple pulmonary artery reconstruction, we have not yet used VATS for more complex surgical procedures, since it is still unclear whether VATS is superior in terms of degree of surgical invasiveness and oncological efficacy when compared with thoracotomy.

Diverse involvement of isoforms and gene aberrations of Akt in human lung carcinomas.

Emerging evidence confirms a central role of Akt in cancer. To evaluate the relative contribution of deregulated Akt and their clinicopathological significance in lung carcinomas, overexpression, activation of Akt and AKT gene increases were investigated. Immunohistochemical staining for 108 cases revealed overexpression of total Akt, Akt1, Akt2 and Akt3 in 61.1, 47.2, 40.7 and 23.1%, respectively, and phosphorylated Akt in 42.6% of cases. Expression of total Akt, Akt2 and Akt3 were frequently observed in small cell carcinoma, but phosphorylated Akt and Akt1 were more frequently observed in squamous cell carcinoma. FISH analysis to evaluate gene increases of AKT1-3 revealed amplification of AKT1 in 4.2% and AKT1 increase by polysomy of chromosome 14 in 27.3% of cases. For AKT2, amplification was observed in 3.2% and polysomy of chromosome 19 in 26.3% of cases. AKT3 increase was observed in 40.0% of cases only by polysomy of chromosome 1. Although "FISH-positive" AKT1 and AKT2 gene increases (amplification/high-level polysomy) were found exclusively in the cases overexpressing total Akt, Akt1 or Akt2, respectively, AKT3 increase was irrelevant of Akt3 expression. Statistically, expressions of Akt2, p-Akt and cytoplasmic-p-Akt were correlated with lymph node metastasis (P = 0.0479, P = 0.0371 and P = 0.0310, respectively). Although AKT1 and AKT2 gene increase showed positive correlation with, or trend towards a positive correlation with tumor size (P = 0.0430, P = 0.0590, respectively), AKT3 did not. In conclusion, Akt isoforms are differentially involved in the pathological phenotype of lung carcinoma in a diverse manner. Because abnormality of Akt1/AKT1 and Akt2/AKT2 correlated with clinicopathological profiles, Akt1/2-specific targeting may open a novel therapeutic window for the group showing Akt deregulation.

[Management of patients with ischemic heart disease in lung cancer resection].

We reviewed the medical records of 1,047 consecutive patients with lung cancer who underwent surgery between April 2005 and March 2014. Among them 49 patients(4.7%)had concomitant ischemic heart disease. Coronary angiography showed coronary artery stenosis in 41 patients, of whom 14 patients received bare metal stents and 9 patients received drug-eluting stents. Three patients underwent plain old balloon angioplasty. Coronary artery bypass graft were performed in 5 patients. Eight patients with coronary spastic angina were also included in the present study. Aspirin administration was continued in 9 patients and heparinization was performed in 14 patients during the perioperative period. Postoperative major adverse cardiac events within 30-days occurred in 3 patients(6.1%)resulting in a single fatality(2.0%). No major cardiac events, including stent thrombosis, developed in patient who received coronary stent. Perioperative aspirin administration and heparinization were not significantly associated with intraoperative bleeding during the operation.

[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.

Matrix metalloproteinase­1 and microRNA­486­5p in urinary exosomes can be used to detect early lung cancer: A preliminary report.

The present study describes a novel molecular-genetic method suitable for lung cancer (LC) screening in the work-place and at community health centers. Using urinary-isolated exosomes from 35 patients with LC and 40 healthy volunteers, the expression ratio of MMP-1/CD63, and the relative expression levels of both microRNA (miRNA)-21 and miRNA-486-5p were measured. MMP-1/CD63 expression ratio was significantly higher in patients with LC than in the healthy controls {1.342 [95% confidence interval (CI): 0.890-1.974] vs. 0.600 (0.490-0.900); P<0.0001}. The relative expression of miRNA-486-5p in male healthy controls was significantly different from that in female healthy controls, whereas there was no significant difference in miRNA-21. Receiver operating characteristic curve (ROC) analysis of MMP-1/CD63 showed 92.5% sensitivity and 54.3% specificity, whereas miRNA-486-5p showed 85% sensitivity and 70.8% specificity for men, and 70.0% sensitivity and 72.7% specificity for women. The logistic regression model used to evaluate the association of LC with the combination of MMP-1/CD63 and miRNA-486-5p revealed that the area under the ROC curve was 0.954 (95% CI: 0.908-1.000), and the model had 89% sensitivity and 88% specificity after adjusting for age, sex and smoking status. These data suggested that the combined analysis of MMP-1/CD63 and miRNA-486-5p in urinary exosomes may be used to detect patients with early-stage LC in the work-place and at community health centers, although confirmational studies are warranted.

Expression patterns of HNF4α, TTF-1, and SMARCA4 in lung adenocarcinomas: impacts on clinicopathological and genetic features.

INTRODUCTION: HNF4α expression and SMARCA4 loss were thought to be features of non-terminal respiratory unit (TRU)-type lung adenocarcinomas, but their relationships remained unclear. MATERIALS AND METHODS: HNF4α-positive cases among 241 lung adenocarcinomas were stratified based on TTF-1 and SMARCA4 expressions, histological subtypes, and driver mutations. Immunohistochemical analysis was performed using xenograft tumors of lung adenocarcinoma cell lines with high HNF4A expression. RESULT: HNF4α-positive adenocarcinomas(n = 33) were divided into two groups: the variant group(15 mucinous, 2 enteric, and 1 colloid), where SMARCA4 was retained in all cases, and the conventional non-mucinous group(6 papillary, 5 solid, and 4 acinar), where SMARCA4 was lost in 3/15 cases(20%). All variant cases were negative for TTF-1 and showed wild-type EGFR and frequent KRAS mutations(10/18, 56%). The non-mucinous group was further divided into two groups: TRU-type(n = 7), which was positive for TTF-1 and showed predominantly papillary histology(6/7, 86%) and EGFR mutations(3/7, 43%), and non-TRU-type(n = 8), which was negative for TTF-1, showed frequent loss of SMARCA4(2/8, 25%) and predominantly solid histology(4/8, 50%), and never harbored EGFR mutations. Survival analysis of 230 cases based on histological grading and HNF4α expression revealed that HNF4α-positive poorly differentiated (grade 3) adenocarcinoma showed the worst prognosis. Among 39 cell lines, A549 showed the highest level of HNF4A, immunohistochemically HNF4α expression positive and SMARCA4 lost, and exhibited non-mucinous, high-grade morphology in xenograft tumors. CONCLUSION: HNF4α-positive non-mucinous adenocarcinomas included TRU-type and non-TRU-type cases; the latter tended to exhibit the high-grade phenotype with frequent loss of SMARCA4, and A549 was a representative cell line.

[Stump recurrence after pulmonary metastasectomy from colorectal cancer].

Pulmonary metastasectomy with wedge resection is an ideal procedure in terms of less invasiveness and preservation of respiratory function, while local recurrence is a major problem. The goal of this study was to verify risk factors of stump recurrence after pulmonary metastasectomy from colorectal cancer. Pulmonary metastasectomies including 112 operations for 131 lesions in 85 patients with colorectal cancer were performed in our department since March, 2005 until the end of 2010. In our cases, stump recurrence significantly occurred in patients who underwent wedge resection than segmentectomy or lobectomy. Stump recurrence developed in 14 operations among 62 wedge resections (recurrence rate: 23%). Diameter more than 10 mm and distance between pleura and deepest end of the tumor (depth value) more than 14 mm were risk factors as stump recurrence. Tumor diameter and depth value can be a decisional factor for wedge resection in pulmonary metastasectomy in the colorectal cancer patients.