[Incidentally Found Intralobar Pulmonary Sequestration Undergoing Video-assisted Thoracoscopic Right Basal Segmentectomy:Report of a Case].

A 53-year-old asymptomatic woman was admitted to our hospital for evaluation of an area of abnormal intensity in the right lower lobe on cardiovascular magnetic resonance imaging. She denied a history of pneumonia but occasionally expectorated bloody sputum. Contrast-enhanced chest computed tomography (CT) revealed areas of consolidations with multiple cysts within the right lower lobe and an anomalous artery that originated from the descending aorta and entered the right lower lobe. Based on contrast-enhanced CT findings, she was diagnosed with intralobar pulmonary sequestration, and we performed video-assisted thoracoscopic right basal segmentectomy. The anomalous artery was identified in the pulmonary ligament and was ligated using a silk suture at its proximal end, after which the peripheral segment was separated using an automatic suture device. The patient had an uneventful postoperative course, and plain CT at the 6-month postoperative follow-up indicated no evidence of edema of the anomalous artery stump. We recommend early surgical resection even in asymptomatic patients with pulmonary sequestration.

Significance of Body Mass Index for Postoperative Outcomes after Lung Cancer Surgery in Elderly Patients.

BACKGROUND: Although the frequency of elderly patients undergoing surgery for lung cancer has been increasing, indications for surgery in elderly patients are still controversial. Low body mass index is a significant predictor of poor prognosis in elderly patients with various medical conditions. Then, we examined the long-term outcome of elderly patients who had undergone thoracic surgery for lung cancer, focusing especially on body mass index. PATIENTS AND METHODS: Between January 2004 and March 2011, 1673 patients with lung cancer underwent surgical resection at our institution. Among these patients, we retrospectively examined 158 patients aged 80 years or older. RESULTS: Perioperative morbidity and mortality rates were 41.8 and 1.3%, respectively. Among 149 patients who were completely followed up, 80 patients (53.7%) died. The overall postoperative survival rates at 3 and 5 years were 66.9 and 49.9%, respectively. Univariate analysis demonstrated that sex (female), smoking index (pack-years <20), histology (non-squamous cell carcinoma), pathological stage (stage I) and BMI (within normal BMI) were statistically significant factors associated with better outcome. Multivariate analysis revealed that patients with a low (<18.5 kg/m2) or high (≥25 kg/m2) body mass index had a significantly and poorer prognosis than patients with a normal body mass index. CONCLUSION: Body mass index is a more useful prognostic factor than other clinical factors including pathological stage in elderly patients. Because elderly patients with low and high body mass index have a significant poor prognosis, surgeons and pulmonologist should take this into account when consider surgical indication for such elderly patients.

[Organizing Pneumonia with High Radiotracer Concentration on Fluorodeoxyglucose-positron Emission Tomography, Mimicking Pleural Dissemination of Lung Cancer;Report of a Case].

A 68-year-old man was referred to our hospital because of an abnormal shadow in the chest roentgenogram. Chest computed tomography (CT) showed the nodule in the right upper lobe (S3), 17 mm in size. One month later, fluorodeoxyglucose-positron emission tomography (FDG-PET)/CT scanning revealed positive reaction in the right upper lobe lesion and new lesion close to another lobe. In addition, interloblar small nodules were detected, 5 mm and 7 mm in size. A transbronchial brush cytology by bronchoscopy was performed, and the microscopic findings demonstrated the presence of atypical cells, suspected adenocarcinoma. The video-assisted thoracoscopic surgery was performed to establish a diagnosis and a treatment. Histopathological examination showed no malignancy and organizing pneumonia with inflammation. In case of the PET-positive solitary nodule increasing in size, organizing pneumonia should be included in the differential diagnosis.

[Interlobar neurinoma with a cystic formation derived from the vagal pulmonary branches].

A 60-year-old woman was referred to our hospital because of an abnormal shadow in the chest roentgenogram. Chest computed tomography (CT) showed the mass with heterogeneous low attenuation in the right lower lobe (S6), 40 mm in size. Fluorodeoxyglucose-positron emission tomography (FDGPET)/CT scanning revealed slight positive reaction in the right lower lobe lesion. The video-assisted thoracoscopic surgery (VATS) was performed to establish diagnosis and treat. Intraoperative finding showed the tumor was located between the left upper lobe and the left lower lobe, and the inflow of the vagal pulmonary branches. Histopathological examination showed no malignancy and neurinoma with a cystic formation derived from the vagus nerve.

Iatrogenic bronchial injury findings during video-assisted thoracoscopic surgery.

Iatrogenic tracheobronchial injury detected during cardiothoracic surgery should be repaired intraoperatively to ensure safe of postoperative management and stable respiratory conditions. We report herein a patient with lung cancer who underwent video-assisted thoracoscopic surgery right lower lobectomy. During surgery, pneumomediastinum and air leakage from mediastinal fatty tissue were detected. Furthermore, bronchial injury to the membranous part of the left main bronchus was incidentally detected. Hence, we switched from video-assisted thoracoscopic surgery to posterolateral thoracotomy and repaired this bronchial injury using a continuous suture technique under right femoral venoarterial extracorporeal membrane oxygenation support. The intraoperative findings could offer a clue for early detection and development of therapeutic strategy for iatrogenic tracheobronchial injury.

Solitary Splenic Metastasis of Lung Cancer Presenting as Benign Cystic Disease.

Solitary splenic metastasis from primary lung cancer is extremely rare. Here, we demonstrated a solitary splenic metastasis of primary lung cancer that was difficult to distinguish from benign cystic disease. A 69-year-old-female was diagnosed as middle lobe lung cancer. Although preoperative abdominal computed tomography (CT) demonstrated a low-density splenic nodule, fluorodeoxyglucose-positron emission tomography (FDG-PET) revealed no fluorodeoxyglucose uptake in the splenic nodule. Therefore, the nodule was diagnosed as benign cystic disease and middle lobe lobectomy was performed. Postoperative pathologic examination demonstrated papillary-predominant adenocarcinoma with mucin, and the tumor was diagnosed as primary lung cancer. However, the splenic nodule continued to increase postoperatively. Splenectomy was undergone 30 months after the pulmonary resection and the splenic tumor was diagnosed as the splenic metastasis of lung cancer. In the 24 months since the splenectomy, no recurrence has been observed in the absence of treatment. Splenectomy was an effective treatment for solitary splenic metastasis of lung cancer in this case. FDG uptake in the splenic tumor was not evident due to marked mucus production.

Delayed bronchial perforation after bulla cauterization with soft coagulation system.

BACKGROUND: Soft coagulation is widely used for hemostasis because of its significant advantage in inducing tissue coagulation and denaturation without carbonization. However, a few cases of airway damage have been reported at the site, where soft coagulation was directly applied. CASE PRESENTATION: We encountered an unusual case of delayed perforation of the intermediate bronchial trunk observed on 24 days after cauterization of the right S6 bulla adjacent to the bronchus. Chest computed tomography revealed a large fistula between the intermediate bronchial trunk and the cauterized bulla in the right S6. Bronchoscopy showed a large fistula at the membranous portion of the intermediate bronchial trunk. We presumed that the bronchial perforation resulted from thermal damage to the intermediate bronchial trunk during bulla cauterization and the bronchial perforation induced infection in the bulla. Resection of the infectious bulla and the intermediate bronchial trunk, followed by end-to-end bronchial anastomosis and a pedicled intercostal muscle flap coverage, was performed. CONCLUSIONS: The severe airway damage resulting in perforation developed even without direct contact between the electrode tip and the bronchial wall, provoking the need for special attention to the duration of cauterization and location, where it is used.

Mutations in Keap1 are a potential prognostic factor in resected non-small cell lung cancer.

BACKGROUND: Mutations in Kelch-like ECH-associated protein 1 (Keap1) have been reported to protect tumor cells from chemotherapeutic agents. However, their prognostic significance in nonsmall cell lung cancer (NSCLC) is still unclear. In this study, we examined the effect of Keap1 gene mutations on survival and disease-free interval using resected primary NSCLC tissue. METHODS: We retrospectively analyzed the tumors from 79 patients with completely resected pathological Stage I-II NSCLC for the presence of Keap1 gene mutations and examined the prognosis of the patients. RESULTS: Keap1 gene mutations were detected in four patients (5.1%). The postoperative 5-year survival rate for patients with Keap1 mutations was significantly lower than those without a mutation (25% vs. 76%, P = 0.038). The postoperative 5-year disease-free survival rate for patients with a mutant Keap1 tumor was slightly lower than for patients with Keap1 wild-type tumors (25% vs. 66%, P = 0.057). CONCLUSIONS: Keap1 gene mutations are likely to be associated with a worse prognosis and lower postoperative disease-free survival rates in pathological Stage I-II NSCLC.

Case report of thoracoscopic resection for broncholithiasis with severe obstructive pneumonia.

Broncholithiasis is a rare disease characterized by bronchial erosion or distortion due to hilar or parenchymatous calcification. When a broncholith has no mobility and there is a risk of major bleeding if removal is attempted, surgical intervention is required. Most operations for broncholithiasis are performed via a thoracotomy, and bronchial lithotripsy under complete video-assisted thoracoscopic surgery has been reported only rarely. We have experienced a case of broncholithiasis with severe obstructive pneumonia that was treated successfully by video-assisted thoracoscopic surgery. Thoracoscopic surgery is an effective treatment for broncholithiasis because it is minimally invasive and aids smooth recovery after surgery. When the adhesion between the pulmonary artery and the bronchus is highly advanced, it is advocated to cut them together using an endostapler.

Contralateral tension pneumothorax during video-assisted thoracic surgery for lung cancer in a patient with obesity and rib fractures: a case report and review of the literature.

BACKGROUND: Intraoperative contralateral pneumothorax during one-lung ventilation is a rare but life-threatening complication. Although the exact incidence is unknown, only 14 cases with this complication have been reported until now. CASE PRESENTATION: A 67-year-old Japanese man with a weight of 80 kg, height of 162.2 cm, and body mass index of 30.4 kg/m2 underwent three-port video-assisted thoracic surgery for lung cancer with one-lung ventilation. He had suffered from traumatic right rib fractures 6 weeks before the referral. Fifteen minutes before the end of the surgery, the systolic blood pressure suddenly dropped to about 50 mmHg, which was immediately recovered by intravenous injection of phenylephrine. This episode occurred during chest closure after the completion of the left upper lobectomy, and one-lung ventilation was soon switched to two-lung ventilation. Contralateral tension pneumothorax was noted by the postoperative chest x-ray. As the patient was complicated with obesity and a past history of rib fractures, increased airway pressure during one-lung ventilation related to obesity together with the persistent compression of the visceral pleura by the fractured ends of the ribs was considered to be the factors responsible for this critical complication. CONCLUSIONS: Patient backgrounds such as obesity and past history of rib fractures should be noted carefully as risk factors for intraoperative contralateral pneumothorax during one-lung ventilation. We present the clinical course and discuss the mechanism of development of this potentially life-threatening complication in the present case with a review of the literature.

D2-40-positive lymphatic vessel density is a poor prognostic factor in squamous cell carcinoma of the lung.

BACKGROUND: Experimental studies have revealed that D2-40 is useful in identifying the presence of lymphatic invasion in various malignant neoplasms, but the clinical significance remains unclear. The purpose of this study is to assess the clinical significance of D2-40 status in completely resected non-small cell lung cancer. METHODS: A total of 215 consecutive patients with resected pathological stage I-IIIA non-small cell lung cancer were reviewed. Expression of D2-40 in tumor cells and in endothelial cells was examined immunohistochemically, and D2-40-positive lymphatic vessel density (LVD) at the tumor periphery were quantitatively evaluated. RESULTS: D2-40 expression on tumor cells was positive in 55 (25.6%) of 215 patients, and the incidence was significantly higher in squamous cell carcinoma (SCC) patients than in adenocarcinoma patients (48.8% vs. 8.6%, P < .001). D2-40 was also seen on lymphatic vessels in tumor tissues, and the mean number of D2-40-LVD was significantly decreased along with differentiation of tumor cells (P = .038). For all histologic types of tumors, there was no difference in the postoperative survival between higher D2-40-LVD patients and lower D2-40-LVD patients. For SCC, however, lower D2-40-LVD patients showed a significantly better survival than higher D2-40-LVD patients (5-year survival rates, 52.9% vs. 78.9%, P = .040), which was confirmed by a multivariate analyses (P = .048). CONCLUSIONS: D2-40 expression on tumor cells was more frequently seen in SCC than in adenocarcinoma of the lung. In addition, D2-40 expression on lymphatic vessels in tumor tissues was a statistically significant prognostic factor in SCC.

Nodule around the staple line after pulmonary resection: benign granuloma or cancer recurrence?

PURPOSE: When a mass develops around the staple line after lung cancer surgery, differential diagnosis between lung cancer recurrence and benign granuloma can be clinically problematic. Therefore, we investigated the clinical characteristics of benign granuloma and cancer recurrence around the staple line to determine clinical factors that can distinguish staple line granuloma and cancer recurrence. METHODS: We retrospectively investigated the clinical records of 25 patients who developed a nodule around the staple line after pulmonary resection for lung cancer and conducted a comparative study of staple line granuloma and cancer recurrence. RESULTS: Among 25 patients, the nodule was diagnosed as benign granuloma in 9, recurrence of primary lung cancer in 8, and recurrence of metastatic lung cancer in 8. Among these three groups, there were no significant differences in age, maximum standardized uptake value of fluoro-deoxyglucose, laboratory data, or radiological findings. However, in comparison with the cancer recurrence cases, the proportion of patients who had undergone segmentectomy as initial surgery was significantly higher in the granuloma group. Moreover, in five patients in the granuloma group, mycobacterium was detected. CONCLUSION: It seemed difficult to differentiate between cancer recurrence and granuloma on the basis of radiological examination and laboratory findings. However, if a mass shadow around the staple line appeared after segmentectomy, the mass is likely to be a granuloma. Mycobacterial infection may be an important factor for development of granuloma on the staple line.

Preoperative Smoking Cessation Period Is Not Related to Postoperative Respiratory Complications in Patients Undergoing Lung Cancer Surgery.

PURPOSE: Smoking is reported to be a risk factor for postoperative complications. However, there is no consensus regarding the length of time for which patients need to give up smoking. Therefore, we examined the relationship between preoperative smoking status and postoperative complications in patients who underwent lobectomy for treatment of lung cancer. METHODS: Between January 2009 and December 2014, 1380 patients underwent lobectomy for lung cancer at our institution. After excluding patients who had undergone induction therapy, 1248 patients were enrolled in this study. We examined the relationship between postoperative complications and preoperative smoking habitation. RESULTS: Among the enrolled patients, 1210 (97%) underwent video-assisted thoracoscopic lobectomy and 38 (3%) underwent lobectomy via open thoracotomy. The incidence of postoperative complications was higher in smokers than in nonsmokers, and the frequency of respiratory-related complications increased along with the number of pack-years. However, there was no relationship between the length of the preoperative smoking cessation period and the frequency of postoperative complications. CONCLUSION: The risk of postoperative complications does not increase even if smoking is continued within 2 weeks before surgery. It seems unnecessary to delay the timing of surgery to allow patients to cease smoking, especially those scheduled for thoracoscopic surgery.

Expression status of folate receptor alpha is significantly correlated with prognosis in non-small-cell lung cancers.

BACKGROUND: To evaluate the prognostic value of folate receptor alpha (FOLR1) and/or reduced folate carrier (RFC1) expression, which are well-characterized folate transporters, in completely resected non-small-cell lung cancer (NSCLC). METHODS: We quantitatively examined gene expression of FOLR1 and RFC1 in surgical specimens resected from NSCLC patients. A total of 119 consecutive patients from January 2003 to June 2004 were included. RESULTS: In adenocarcinoma, the FOLR1 gene expression was downregulated in smokers and male patients (P = 0.006 and P < 0.001, respectively). In addition, FOLR1 expression values in patients with well-differentiated, early p-stage, pT1, pN0, EGFR mutant, and p53 wild-type cancers were significantly higher than those for poorly differentiated, advanced p-stage, pT2-4, pN1-3, EGFR wild-type, and p53 mutant (P < 0.001, P < 0.001, P < 0.001, P = 0.002, P < 0.001 and P = 0.023, respectively). In squamous cell carcinoma, FOLR1 expression values in patients with pN1-3 was significantly higher than those with pN0 (P = 0.037). Moreover, the 3-year survival rate and disease-free survival rate of high-FOLR1-expressing patients (94.7% and 75.4%) were significantly higher than those of low-FOLR1-expressing patients (80.9% and 60.8%) (P = 0.008 and P = 0.038). A multivariate analysis confirmed that high FOLR1 expression was an independent and significant factor predicting a favorable prognosis (P = 0.043). CONCLUSIONS: Higher levels of FOLR1 appear to be associated with better prognoses for patients with lung adenocarcinomas.

Schedule-dependent synergistic effect of pemetrexed combined with gemcitabine against malignant pleural mesothelioma and non-small cell lung cancer cell lines.

BACKGROUND: Pemetrexed, a multi-targeted antifolate (MTA), is a promising agent in the treatment of malignant pleural mesothelioma (MPM) and non-small cell lung cancer (NSCLC). With the aim of finding an optimal schedule for the combination therapy of MTA and gemcitabine (GEM), we investigated their interaction against an MPM cell line, 211H, and the NSCLC cell lines A549 and H1299. METHODS: Combination index analysis was used in 3 different schedules. Cell cycle analysis by flow cytometry and real-time RT-PCR analysis of thymidylate synthase (TS), folylpolyglutamate synthetase (FPGS) and reduced folate carrier 1 (RFC1) genes were performed to understand the biological consequences of their interaction. RESULTS: MTA showed potent cytotoxicity against 211H cells (IC(50), 67 nM for 48 h exposure), compared to NSCLC cell lines. Significantly higher expression of FPGS and RFC1 mRNAs in 211H cells were associated with MTA sensitivity. Simultaneous exposure of MTA and GEM was antagonistic in all cell lines tested. Strong synergism was observed in 211H cells when MTA preceded GEM, but the inverted sequence showed antagonism. Similar results were exhibited in H1299 cells, whereas a moderately synergistic effect was observed in A549 cells when GEM preceded MTA. S phase accumulation by MTA treatment partly supported these results. CONCLUSION: Sequential administration of MTA and GEM is active, and the schedule of MTA followed by GEM is recommended for treating MPM.

Video-assisted thoracoscopic surgery for lung cancer after induction therapy.

Background Although thoracoscopic surgery is widely performed for early-stage lung cancer, only a few small studies have evaluated the role of video-assisted thoracoscopic surgery in patients with locally advanced lung cancer who had received preoperative chemotherapy. Methods Among 1655 patients who underwent anatomical lung resection for lung cancer between January 2009 and December 2014 in our institution, we retrospectively examined the short- and long-term outcomes of 110 (6.6%) who had undergone induction therapy. Thoracoscopic surgery was performed in 79 of these patients and thoracotomy in 31. Results In the thoracoscopic group, conversion to a thoracotomy was required in 4 patients. More combined resections were included in the thoracotomy group, and combined resection of large vessels or the carina was carried out only via a thoracotomy. Postoperative complications of grade 3 or above were found in 15 (13.6%) patients, and there was no significant difference in the incidence of postoperative complications between the 2 groups. The 3- and 5-year survival rates for the patients overall were 58.6% and 50.3%, respectively. Although there was no significant difference in overall outcome between the 2 groups, the patients with postoperative ypN2 status in the thoracoscopic group had a significantly better outcome than those in the thoracotomy group. Conclusion Although video-assisted thoracoscopic surgery was not suitable for central advanced lung cancer requiring angioplasty or carinal resection, it seems to be useful for patients with locally advanced lung cancer who had undergone induction therapy, especially patients with peripheral lung cancer and mediastinal lymph node metastasis.

The outcomes of anatomical lung resection for nontuberculous mycobacterial lung disease.

BACKGROUND: The number of cases of nontuberculous mycobacterial (NTM) lung disease has been increasing in recent years, and the efficacy of surgical treatment has been recognized. We investigated the clinical characteristics and behavior of NTM lung disease and analyzed the outcomes of surgery. METHODS: The data of 25 patients who underwent anatomical resection for NTM lung disease in our institution between January 2004 and December 2014 were retrospectively examined. RESULTS: The patients included 10 men and 15 women (mean age, 63.1 years). Twenty patients had Mycobacterium avium, and 5 had Mycobacterium intracellular. The indications for lung resection in 20 definitively diagnosed patients included a remaining or worsening lesion despite medical treatment (n=16), massive hemoptysis or bloody sputum (n=5), and prolonged smear positivity (n=1); multiple reasons were allowed. In five cases without a definitive diagnosis, surgery was performed due to the suspicion of lung cancer. The surgical procedures included pneumonectomy, n=4; lobectomy, n=13; and segmentectomy, n=8. Complete resection was achieved in 10 cases (40.0%). Video-assisted thoracoscopic surgery (VATS) was performed in 17 cases (68.0%), especially in 6 of 8 cases (75.0%) that underwent segmentectomy and in 10 of 11 cases (90.9%) that received simple lobectomy. There was one case of hospital mortality. Among the 22 patients who were followed at our institution, relapse occurred in 4 patients, and new infection occurred in 1 patient. NTM lung disease was controlled in 17 patients (77.3%). In the four cases that relapsed, the median relapse-free interval was 29.5 months. CONCLUSIONS: Surgical resection was a feasible treatment for NTM lung disease and was associated with favorable outcomes, although there was 1 case of hospital mortality. VATS procedures were considered adequate for the treatment of NTM lung disease; however, the surgical indications must be carefully considered.

Phrenic Nerve Reconstruction and Bilateral Diaphragm Plication After Lobectomy.

A 49-year-old man with left phrenic nerve paralysis caused by mediastinal tumor resection 28 years earlier was found to have a nodule in the right upper lobe. The right phrenic nerve was severed during right upper lobectomy but was reconstructed along with bilateral plication of the diaphragm. The patient was weaned from the ventilator during the daytime on postoperative day 13 and was discharged home on postoperative day 48. Three months postoperatively, chest fluoroscopic imaging showed recovery of movement of the right diaphragm. Nerve conduction studies showed improvement of function of the reconstructed right phrenic nerve.

Upregulated heme biosynthesis, an exploitable vulnerability in MYCN-driven leukemogenesis.

The increased heme biosynthesis long observed in leukemia was previously of unknown significance. Heme, synthesized from porphyrin precursors, plays a central role in oxygen metabolism and mitochondrial function, yet little is known about its role in leukemogenesis. Here, we show increased expression of heme biosynthetic genes, including UROD, only in pediatric AML samples that have high MYCN expression. High expression of both UROD and MYCN predicts poor overall survival and unfavorable outcomes in adult AML. Murine leukemic progenitors derived from hematopoietic progenitor cells (HPCs) overexpressing a MYCN cDNA (MYCN-HPCs) require heme/porphyrin biosynthesis, accompanied by increased oxygen consumption, to fully engage in self-renewal and oncogenic transformation. Blocking heme biosynthesis reduced mitochondrial oxygen consumption and markedly suppressed self-renewal. Leukemic progenitors rely on balanced production of heme and heme intermediates, the porphyrins. Porphyrin homeostasis is required because absence of the porphyrin exporter, ABCG2, increased death of leukemic progenitors in vitro and prolonged the survival of mice transplanted with Abcg2-KO MYCN-HPCs. Pediatric AML patients with elevated MYCN mRNA display strong activation of TP53 target genes. Abcg2-KO MYCN-HPCs were rescued from porphyrin toxicity by p53 loss. This vulnerability was exploited to show that treatment with a porphyrin precursor, coupled with the absence of ABCG2, blocked MYCN-driven leukemogenesis in vivo, thereby demonstrating that porphyrin homeostasis is a pathway crucial to MYCN leukemogenesis.