Tomoki Shibano

Dangerous mediastinal basal pulmonary artery during left upper lobectomy

Anatomical variations in the pulmonary vessels present a potential risk for intraoperative bleeding and damage to the pulmonary circulation during pulmonary resection. Here, we present a patient who underwent left upper lobectomy for lung cancer. The patient had a dangerous mediastinal basal pulmonary artery variation that could be mistaken for the mediastinal lingular pulmonary artery and be divided during left upper lobectomy.

Establishment of highly metastatic KRAS mutant lung cancer cell sublines in long-term three-dimensional low attachment cultures

Decreased cell-substratum adhesion is crucially involved in metastasis. Previous studies demonstrated that lung cancer with floating cell clusters in histology is more likely to develop metastasis. In the present study, we investigated whether cancer cells in long-term, three-dimensional low attachment cultures acquire high metastatic potential; these cells were then used to examine the mechanisms underlying metastasis. Two KRAS-mutated adenocarcinoma cell lines (A549 and H441) were cultured and selected on ultra-low attachment culture dishes, and the resulting cells were defined as FL (for floating) sublines. Cancer cells were inoculated into NOD/SCID mice via an intracardiac injection, and metastasis was evaluated using luciferase-based imaging and histopathology. In vitro cell growth (in attachment or suspension cultures), migration, and invasion were assayed. A whole genomic analysis was performed to identify key molecular alterations in FL sublines. Upon detachment on low-binding dishes, parental cells initially formed rounded spheroids with limited growth activity. However, over time in cultures, cells gradually formed smaller spheroids that grew slowly, and, after 3–4 months, we obtained FL sublines that regained prominent growth potential in suspension cultures. On ordinary dishes, FL cells reattached and exhibited a more spindle-shaped morphology than parental cells. No marked differences were observed in cell growth with attachment, migration, or invasion between FL sublines and parental cell lines; however, FL cells exhibited markedly increased growth potential under suspended conditions in vitro and stronger metastatic abilities in vivo. A genomic analysis identified epithelial-mesenchymal transition (EMT) and c-Myc amplification in A549-FL and H441-FL cells, respectively, as candidate mechanisms for metastasis. The growth potential of FL cells was markedly inhibited by lentiviral ZEB1 knockdown in A549-FL cells and by the inhibition of c-Myc through lentiviral knockdown or the pharmacological inhibitor JQ1 in H441-FL cells. Long-term three-dimensional low attachment cultures may become a useful method for investigating the mechanisms underlying metastasis mediated by decreased cell-substratum adhesion.

Recommendations for perioperative management of lung cancer patients with comorbidities

ObjectivesTo improve surgical outcomes, clinicians must provide optimal perioperative care for comorbidities identified as significant factors in risk models for patients undergoing lung cancer surgery.MethodsWe reviewed trends in perioperative care for idiopathic pulmonary fibrosis, cardiovascular diseases, and end-stage renal diseases in patients undergoing lung cancer surgery, as large clinical databases indicate that these comorbidities are significant risk factors for lung cancer surgery. Articles identified by keyword searches were included in the analysis.ResultsSignificant predictive factors for acute exacerbation of idiopathic pulmonary fibrosis were identified. However, no effective perioperative care was identified for prevention of acute exacerbation of interstitial pneumonia. The timing of coronary revascularization and antithrombotic management for cardiovascular diseases are subjects of ongoing research, and acid–base balance is essential in the management of hemodialysis patients with end-stage renal diseases.ConclusionsTo improve surgical outcomes for lung cancer patients, future studies should continue to study optimal perioperative management of comorbidities.

Polyglycolic acid mesh occlusion for postoperative bronchopleural fistula.

Background Postoperative bronchopleural fistula is one of the most life-threatening complications after anatomical pulmonary resection. Bronchopleural fistula may cause empyema and aspiration pneumonia with subsequent acute respiratory distress syndrome. Surgical interventions for bronchopleural fistula can prolong hospitalization and impair postoperative quality of life. Postoperative care requires minimally invasive endoscopic occlusion. Methods We retrospectively reviewed the records of 7 patients who developed bronchopleural fistula among 689 patients who underwent segmentectomy or lobectomy without sleeve resection for lung cancer in Jichi Medical University from 2009 to 2013. Bronchopleural fistula occurred in the right lower bronchial stump in 3 patients, in the superior segmental bronchus of the right lower lobe in 2, in the superior segmental bronchus of the left lower lobe in one, and in the right intermediate bronchus in one. Flexible bronchoscopy was used to occlude 3-mm fistulas with polyglycolic acid mesh in 2 patients. Larger fistulas in 5 patients were occluded with polyglycolic acid mesh plus fibrin glue to secure the mesh. The median procedure was 37 min. Procedures were considered complete upon resolution of air leakage from the chest drainage system. Results Bronchoscopic interventions for bronchopleural fistula were repeated an average of 2 times. No procedure-related complications or death occurred. Bronchoscopic interventions were successful in all patients. Conclusions Bronchoscopic occlusion with polyglycolic acid mesh with or without fibrin glue is easy and feasible as the first step in postoperative management of bronchopleural fistula.

Inactivating mutations and hypermethylation of the NKX2-1/TTF-1 gene in non-terminal respiratory unit-type lung adenocarcinomas

The major driver mutations of lung cancer, EGFR mutations and EML4‐ALK fusion, are mainly detected in terminal respiratory unit (TRU)‐type lung adenocarcinomas, which typically show lepidic and/or papillary patterns, but are rarely associated with a solid or invasive mucinous morphology. In order to elucidate the key genetic events in non‐TRU‐type lung cancer, we carried out whole‐exome sequencing on 43 non‐TRU‐type lung adenocarcinomas based on morphology (17 acinar, nine solid, and two enteric adenocarcinomas, and 15 adenocarcinomas with a mucinous morphology). Our analysis identified mutations in TP53 (16/43, 37.2%), KRAS (13/43, 30.2%), and NKX2‐1/TTF‐1 (7/43; 16.3%) as the top three significantly mutated genes, while the EGFR mutation was rare (1/43, 2.3%) in this cohort. Eight NKX2‐1/TTF‐1 mutations (five frameshift, two nonsense, and one missense) were identified, with one case harboring two distinct NKX2‐1/TTF‐1 mutations (one missense and one frameshift). Functional assays with the NK2 homeobox 1 (NKX2‐1)/thyroid transcription factor 1 (TTF‐1) mutants revealed that none of them retain the activity as a transcriptional factor. Histologically, invasive mucinous adenocarcinomas accounted for most of the NKX2‐1/TTF‐1 mutations (five cases), as well as one enteric and one acinar adenocarcinoma. Immunohistochemistry showed that the cohort was largely divided into TTF‐1‐postive/hepatocyte nuclear factor 4‐α (HNF4‐α)‐negative and TTF‐1‐negative/HNF4‐α‐positive groups. NKX2‐1/TTF‐1 mutations were exclusively found in the latter, in which the gastrointestinal markers, mucin 5AC and cytokeratin 20, were frequently expressed. Bisulfite sequencing revealed that the NKX2‐1/TTF‐1 gene body was highly methylated in NKX2‐1/TTF‐1‐negative cases, including those without the NKX2‐1/TTF‐1 mutations. The genetic or epigenetic inactivation of NKX2‐1/TTF‐1 may play an essential role in the development and aberrant differentiation of non‐TRU‐type lung adenocarcinomas.

Revival of impaired lung perfusion after sleeve lobectomy

Sleeve resection, a mainstay for centrally-located lung cancer, is a challenging procedure when the preserved lung is impaired. We herein reported a 61-year-old male who underwent right upper sleeve lobectomy for squamous cell carcinoma located at the orifice of the upper bronchus. The tumor invaded the main bronchus. A lung perfusion scan showed severe impairment, while the right middle and lower lobes were well expanded. Not only the spirogram, but also the lung perfusion in the residual lung, had markedly recovered at 2 months after the right upper extended sleeve lobectomy. The patient is currently living his normal daily life. Residual lung perfusion can be revived, even if it is impaired preoperatively.

Incidental bronchial injury by soft coagulation

Soft coagulation is a hemostat system of electrosurgical units, which automatically regulates its output voltage below 200 V, to avoid excessive output that causes carbonization of the target tissue. However, this new minimally invasive technology still has the potential risk of tissue damage during surgery. We encountered three patients with bronchial injury caused by the above system; one of whom had bronchopleural fistula. This is believed to be the first report emphasizing the adverse effects of the soft coagulation system in thoracic surgery, giving a warning to the application of this convenient device.

Aberrant aneurysm of adult-type pulmonary sequestration: report of a case

Aberrant pulmonary artery exposed by high-blood pressure over a long period in adult-type pulmonary sequestration can be susceptible to arteriosclerotic change and aneurysmal formation. Dividing this aneurysmal artery has a risk of stump leakage and aneurysm. We herein report a 64-year-old man with an aberrant aneurysm of intralobar pulmonary sequestration. Thoracoscopic resection of the sequestrated lung was performed uneventfully by prior endovascular occlusion of the aberrant aneurysm.

Left pneumonectomy for complex aspergilloma after patent ductus arteriosus ligation.

Surgery for complex pulmonary aspergilloma is known to be technically challenging, often for indurated hilar structures and obliterated pleural space. We report a case of left pneumonectomy for pulmonary aspergilloma with a history of patent ductus arteriosus ligation via anterolateral thoracotomy and aortopexy via median sternotomy and pericardiotomy. Left pneumonectomy was successfully accomplished by devising a surgical approach and procedures for transection of the left main pulmonary artery.