Naoko Ose

Lymph node metastasis diagnosis using positron emission tomography with 2-[18F] fluoro-2-deoxy-d-glucose as a tracer and computed tomography in surgical cases of non-small cell lung cancer

OBJECTIVES Positron emission tomography with 2-[18F] fluoro-2-deoxy-D-glucose as a tracer and computed tomography (FDG-PET/CT) are utilized for the diagnosis of lymph node (LN) metastasis from lung cancer. In this study, we analyzed the diagnostic ability of FDG-PET for N staging by focusing on the clinical features of false-positive (FP) and false-negative (FN) cases. METHODS From March 2006 to February 2010, 112 patients underwent preoperative examinations using FDG-PET/CT followed by radical resection with hilar and mediastinal dissection. We analyzed their clinicopathological characteristics based on preoperative FDG-PET/CT findings and post-operative histopathological diagnosis of resected LNs. RESULTS Based on the PET/CT results, 17 patients were misdiagnosed (9 FN and 8 FP). The sensitivity, specificity, accuracy and negative and positive predictive values for N1/N2 were 50.0, 94.5, 84.0, 93.0 and 58.3%, respectively, whereas those for N2 were 57.8, 90.3, 84.8, 90.3 and 61.1%, respectively. FP findings more frequently occurred in cases with elevated white blood cell (WBC) count (P=0.015) and smokers (P=0.04). In the FN group, the maximum standardized uptake value for the primary tumour was lower than that in the true-positive (TP) group (P=0.01). The short-axis sizes of 71 LNs differently diagnosed by PET/CT and histopathology findings were significantly smaller in the FN group than the TP group (P<0.001), whereas there was no difference between TP and FP. As for FN LNs in the TP group, there was no significant difference. CONCLUSIONS PET/CT showed a good ability to detect metastatic LNs, especially for N2 diagnosis. However, there were some limitations, especially in cases with elevated peripheral WBC count and/or smoking history.

A Double-Blind Placebo-Controlled Study of the Effects of Olprinone, a Specific Phosphodiesterase III Inhibitor, for Preventing Postoperative Atrial Fibrillation in Patients Undergoing Pulmonary Resection for Lung Cancer.

BACKGROUND We previously reported that patients with elevated preoperative B-type natriuretic peptide (BNP) levels have an increased risk for postoperative atrial fibrillation following lung cancer surgery. The present study evaluated whether the specific phosphodiesterase III inhibitor olprinone can reduce the incidence of postoperative atrial fibrillation in patients with elevated BNP levels undergoing pulmonary resection for lung cancer. METHODS A prospective randomized study was conducted with 40 patients who had elevated preoperative BNP levels (≥ 30 pg/mL) and underwent scheduled lung cancer surgery. All patients were in sinus rhythm at surgery. Low-dose olprinone or placebo was continuously infused for 24 h and started just before anesthesia induction. The primary end point was the incidence of postoperative atrial fibrillation. The secondary end points were perioperative hemodynamics and levels of BNP, WBC counts, and C-reactive protein. RESULTS The incidence of postoperative atrial fibrillation was significantly lower in the olprinone group than in the placebo group (10% vs 60%, P < .001). Patients in the olprinone group showed significantly lower BNP, WBC counts, and C-reactive protein levels after surgery. CONCLUSIONS Continuous infusion of olprinone during lung cancer surgery was safe and reduced the incidence of postoperative atrial fibrillation following pulmonary resection in patients with elevated preoperative BNP levels. TRIAL REGISTRY Japan Primary Registries Network; No.: JPRN-UMIN2404; URL: http://www.umin.ac.jp/ctr/.

Lymphatic invasion of micropapillary cancer cells is associated with a poor prognosis of pathological stage IA lung adenocarcinomas.

The cancer cells of lung adenocarcinoma with a micropapillary pattern (MPP) have been found to frequently invade lymphatic vessels, and the prognosis of patients with lung adenocarcinoma with an MPP is poor. In the present study, the cancer cells of lung adenocarcinomas containing an MPP were found to express vimentin more extensively than those in lung adenocarcinoma without an MPP. The contribution of cancer cells in the MPP component to adenocarcinoma lymphatic invasion was assessed using vimentin as a marker. Vimentin expression was analyzed in the cancer cells present in each lymphatic vessel and compared with the expression of vimentin in the cancer cells in the adenocarcinomas without an MPP component. The results showed that the cancer cells in the lymphatic vessels expressed vimentin more extensively than those in the adenocarcinoma components without an MPP, suggesting that cancer cells derived from an MPP component are present in the lymphatic vessels. By contrast, the area of the MPP component in each adenocarcinoma was <25%. These findings suggest that cancer cells in MPP components have a high capacity to invade lymphatic vessels and that their high invasive capacity may be associated with a poor prognosis in patients with adenocarcinoma with an MPP component.

Results of treatment for thymic neuroendocrine tumours: multicentre clinicopathological study

OBJECTIVES A thymic neuroendocrine tumour (TNET) is rare, and few comprehensive reports of treatment results have been presented. To clarify the clinicopathological characteristics of TNET in affected patients, outcomes were retrospectively examined using cases accumulated in a multicentre survey. METHODS Thirty patients (25 men and 5 women) who underwent surgical resection or biopsy procedures at 10 institutions of the Thoracic Surgery Study Group of Osaka University (TSSGO) between January 1986 and June 2015 and pathologically diagnosed with TNET were enrolled. RESULTS The examined tumours were classified as typical carcinoid in 7 patients, atypical carcinoid in 11 patients, large-cell neuroendocrine carcinoma in 3 patients and small-cell carcinoma in 9 patients, of which 2 underwent surgical biopsy procedures and 28 surgical resection, with a macroscopic complete resection procedure performed in 27 patients. Induction therapy was performed in 2 patients and adjuvant therapy in 10 patients. Thirteen patients had recurrence, with distant metastasis, especially in bone and lung tissues, more frequent than local recurrence. Overall survival was 77% after 5 years and 35% after 10 years, whereas relapse-free survival was 48% and 29%, and cancer-specific survival was 90% and 48%, respectively. Overall survival was significantly better in patients who underwent macroscopic complete resection (P = 0.010). As for relapse-free survival patients, TNM Stage I or II (P = 0.011) and received adjuvant therapy patients (P = 0.042) showed good survival rates. CONCLUSIONS The prognosis of patients with TNET was favourable in those treated with macroscopic complete resection. Survival is promising even in patients with postoperative recurrence, following treatment utilized for pulmonary neuroendocrine tumour or gastroenteropancreatic neuroendocrine tumour.

Successful removal of expandable metallic stent in a patient with lung cancer.

A 64-year-old man, who had received chemoradiation therapy for stage IIIB non-small-cell lung cancer, underwent stent insertion with a covered expandable metallic stent for post-radiation bronchial stenosis. Stenosis due to formation of granulation tissue at the distal stent site resulted in critical respiratory failure. The stent was removed after 43 months, using rigid bronchoscopy.

VATS thymectomy—bilateral approach for extended resection

Various bilateral VATS thymectomy procedures were introduced in the 1990’s, of which a bilateral VATS extended thymectomy has an advantage of confirming the bilateral phrenic nerves and seems to be the most conventional method in use. Soon after introduction of the method, an anterior cervical incision approach was added, because peri-thymic tissues are thought to reside mostly around the upper poles of the thymus. Studies have shown that significant amounts of thymic and peri-thymic tissues are left behind without use of a cervical incision. Later, several additional techniques, including elevation of the sternum, division of the right internal thoracic vein, and CO 2 insufflation, served to make a cervical incision unnecessary and also providing a cosmetic advantage. Nevertheless, this procedure is still thought to be more invasive than a unilateral approach in terms of longer procedure time and bilateral thoracic incision. Recently, a uniportal bilateral approach was reported and advancement to a reduced port might be a means for achieving a less invasive approach for a bilateral VATS extended thymectomy.

Air leak pattern shown by digital chest drainage system predict prolonged air leakage after pulmonary resection for patients with lung cancer

Background A common cause of complications after a pulmonary resection procedure is prolonged air leakage. Recently introduced digital drainage systems provide accurate recording of air leak data for later review. We investigated the clinical usefulness of the continuous stream of data recorded by such a device. Methods We analyzed data obtained from 299 patients with pulmonary malignancy who underwent a pulmonary resection procedure for lung cancer patients with use of a digital chest drainage system. Postoperative air leak patterns were divided into 4 groups and their correlation with prolonged air leakage after pulmonary resection was evaluated. Results The incidence of prolonged air leak was 10% (30/299). The postoperative air leak patterns noted in the present patients were divided into none (n=217, 73%), intermittent (n=21, 7%), decrease (n=40, 13%), and variable (n=21, 7%). The incidence of prolonged air leak in each group was 0.5% (1/217) in the none group, 24% (5/21) in the intermittent group, 20% (8/40) in the decrease group, and 76% (16/21) in the variable group. The amount of air leakage immediately after surgery was highest in the variable group. Patients in the intermittent and variable groups had longer durations of air leakage and chest tube placement. The frequency of postoperative interventional treatment was significantly higher in the variable group as compared to the others. Chest tube reinsertion for pneumothorax and increased subcutaneous emphysema after the initial chest tube removal was only seen in the intermittent group. Conclusions Advantages of digital drainage system use are continuous monitoring and recording capabilities, which show the detailed air leak pattern after pulmonary resection. That pattern can be used to predict the durations of air leakage and chest tube drainage, as well as for producing an air leak management algorithm.

Long-term outcomes of advanced thymoma in patients undergoing preoperative chemotherapy or chemoradiotherapy followed by surgery: a 20-year experience

OBJECTIVES The results of preoperative chemotherapy or chemoradiotherapy followed by surgery for locally advanced thymoma were analysed. METHODS Between 1997 and 2016, 29 patients with a thymoma underwent preoperative chemotherapy or chemoradiotherapy followed by surgery. These cases were retrospectively reviewed. RESULTS The study population included 9 men and 20 women, with a mean age of 48.8 years (range 31-68 years). The preoperative Masaoka stage was III in 12, IVa in 13 and IVb in 4 patients, whereas histological type was B3 in 11, B2 in 9 and others in 5 patients. The mean tumour size was 8.0 ± 2.5 cm (3.4-15.0 cm). The site of infiltration shown in preoperative radiological examinations was the aorta in 6 patients, the superior vena cava in 14 patients and the pulmonary artery trunk in 3 patients, with pleural dissemination detected in 14. Three patients underwent chemoradiotherapy. Chemotherapy regimens given were cisplatin + doxorubicin + vincristine + cyclophosphamide in 9 patients, carboplatin + paclitaxel in 6 patients, cisplatin + doxorubicin + methylprednisolone in 5 patients and others in 9 patients, with partial response obtained in 11 patients and stable disease noted in 18 patients. Complete resection was achieved in 24 (83%) cases. There were no perioperative mortalities, whereas 6 (21%) patients developed postoperative complications. The 5- and 10-year overall survival rates were 100% and 87%, respectively, and 5- and 10-year disease-free survival rates were 50% and 50%, respectively. CONCLUSIONS Preoperative chemotherapy or chemoradiotherapy followed by surgery for locally advanced thymoma can be performed with an acceptable degree of surgical risk. Such a strategy should be proactively considered, as it can lead to favourable long-term results.

Carnosol suppresses IL-6 production in mouse lungs injured by ischemia-reperfusion operation and in RAW264.7 macrophages treated with lipopolysaccharide

Carnosol is a naturally occurring herbal compound, known for its antioxidative properties. We previously found that carnosol protected mouse lungs from ischemia-reperfusion injury in ex vivo cultures. To elucidate the molecular mechanisms underpinning carnosol-mediated lung protection, we analyzed modes of interleukin-6 (IL-6) gene expression, which is associated with lung ischemia-reperfusion injury. Microarray analysis of mouse lungs suggested that IL-6 mRNA levels were elevated in the mouse lungs subjected to clamp-reperfusion, which was associated with elevated levels of other inflammatory modulators, such as activating transcription factor 3 (ATF3). Carnosol pretreatment lowered the IL-6 protein levels in mouse lung homogenates prepared after the clamp-reperfusion. On the other hand, the ATF3 gene expression was negatively correlated with that of IL-6 in RAW264.7 cells. IL-6 mRNA levels and gene promoter activities were suppressed by carnosol in RAW264.7 cells, but rescued by ATF3 knockdown. When RAW264.7 cells were subjected to hypoxia-reoxygenation, carnosol treatment lowered oxygen consumption after reoxygenation, which was coupled with a correlation with a transient production of mitochondrial reactive oxygen species and following ATF3 gene expression. These results suggest that carnosol treatment could be a new strategy for protecting lungs from ischemia-reperfusion injury by modulating the ATF3-IL-6 axis.

Colopleural fistula caused by aspergillus: an extremely rare complication after lung resection-case report.

A colopleural fistula is a rare condition reported to be caused by Crohn’s disease, a malignant tumor of the gastrointestinal tract, and other clinical conditions. Some studies have noted that a sub-diaphragmatic abscess, usually organized following abdominal surgery, may play some role in the formation of this type of fistula. Therefore, a colopleural fistula is a complication very rarely encountered by thoracic surgeons after lung resection.We experienced an extremely rare case of colopleural fistula following a left lower lobectomy for lung aspergillosis. Here, we report a 71-year-old man with a surgical history of proximal gastrectomy for gastric cancer. He underwent left lower lobectomy of the lung for aspergillosis, and a colopleural fistula occurred on the second operative day as a complication. Aspergillus might be responsible for forming a fistula between the colon and lung via the diaphragm, and lung surgery manifested this rare condition. Although some reports suggest that surgical treatment is mandatory to cure this fistula, an immediate colostomy in our case reduced the internal pressure of the colon, thus enabling spontaneous closure of the fistula with appropriate drainage and antibiotics. The patient was discharged in a good condition.