Tetsuhiko Go

Usefulness of [18F]fluoro-2-deoxy-D-glucose positron emission tomography for predicting the World Health Organization malignancy grade of thymic epithelial tumors

OBJECTIVE The objective of this study was to investigate whether the maximum standardized uptake value (SUVmax) determined using positron emission tomography with [(18)F]fluoro-2-deoxy-D-glucose ((18)FDG-PET) can predict the grade of malignancy of thymic epithelial tumors based on the World Health Organization (WHO) classification. METHODS We retrospectively analyzed 13 patients with thymic epithelial tumors, who underwent (18)FDG-PET examination before treatment. The patients were subdivided into a thymoma group and a thymic carcinoma group, and the two were compared clinicopathologically. RESULTS There were six men and seven women, ranging in age from 36 to 78 years (mean, 58.8 ± 13.3 years). Mean tumor size was 47.3 ± 26.0mm, and the WHO classification was type A in two patients, type AB in none, type B1 in one, type B2 in three, type B3 in two, and thymic carcinoma in five. Thus, eight patients had thymoma and five had thymic carcinoma. The Masaoka stage was I in four patients, II in four, III in three, and IV in two. Mean pre-treatment SUVmax for the tumors overall was 5.24 ± 3.10, with a range of 1.73-11.21. Mean SUVmax in the thymic carcinoma group was 8.15 ± 7.88, and that in the thymoma group was 3.43 ± 2.19, the difference being significant (P = 0.002). CONCLUSIONS A significant relationship was observed between SUVmax and morphological classification by the WHO system for this cohort of thymic epithelial tumors. Pre-treatment SUVmax may be useful for differentiating thymoma from thymic carcinoma.

Clinical trial of new methods for identifying lung intersegmental borders using infrared thoracoscopy with indocyanine green: comparative analysis of 2- and 1-wavelength methods

OBJECTIVES Infrared thoracoscopy is a new method of identifying lung intersegmental borders. This study compared the efficacy of 2- and 1-wavelength infrared thoracoscopy. METHODS A total of 30 consecutive patients who underwent segmentectomy were evaluated by these methods (2-wavelength method, 10 patients; 1-wavelength method, 20 patients). We ligated the dominant pulmonary artery and then observed the lung using an infrared thoracoscope after indocyanine green (ICG) intravenous injection. The 2-wavelength infrared thoracoscope irradiation and detection were conducted at 940 and 805 nm, respectively, and the images were projected based on the difference of the two reflected wavelengths. ICG absorbs 805 nm wavelength light, and the ICG distribution area appears blue against a white background. On the other hand, the 1-wavelength infrared thoracoscope irradiation and detection were conducted at 780 and 830 nm, respectively. The area stained with ICG shows fluorescence. RESULTS In the 2-wavelength method, 3.0 mg/kg of ICG was administered, and a well-defined white-to-blue border was observed in 9 of 10 patients. The staining duration was 220 (interquartile range, 187-251) s. In the 1-wavelength method, 0.5 mg/kg of ICG was administered, and a well-defined border between areas with or without fluorescence was observed in 19 of 20 patients. The staining duration was 370 (interquartile range, 296-440) s, which was significantly longer than the staining duration with the 2-wavelength method (P = 0.0001). CONCLUSIONS Infrared thoracoscopy is useful for detection of intersegmental borders. The dose of ICG for the 1-wavelength method was less than that for 2-wavelength method, and the duration of staining was longer.

Clinicopathological study of p-T1aN0M0 non-small-cell lung cancer, as defined in the seventh edition of the TNM classification of malignant tumors

OBJECTIVE The seventh edition of the TNM Classification of Malignant Tumours was published in 2009. The present study was conducted to investigate the clinicopathological features of p-T1aN0M0 non-small-cell lung cancer, which is the earliest stage defined in the new tumor, node, metastasis (TNM) classification, in relation to patient prognosis. METHODS We retrospectively studied 162 patients, who underwent surgical resection at our institution for p-T1aN0M0 non-small-cell lung cancer, as re-categorized in the seventh TNM classification. Univariate and multivariate analyses of disease-free survival were performed. RESULTS The mean tumor size was 13.2 ± 4.7 mm. The maximum tumor diameter was >10 mm in 104 cases (64.6%), and ≤ 10 mm in 58 (35.4%). The median follow-up period was 44.5 months. Univariate analysis showed that the 5-year disease-free survival rate of patients with and without preoperative serum carcinoembryonic antigen elevation was 50.8% and 95.1% (P<0.0001), respectively, that of patients with and without blood vessel or lymphatic invasion was 40.0% and 95.8% (positive vs negative, P<0.0001), respectively, and that of patients aged ≥ 70 years and <70 years was 86.8% and 96.1% (P=0.014), respectively. Multivariate analysis including these three clinicopathologic factors demonstrated that preoperative elevation of the carcinoembryonic antigen level and blood vessel or lymphatic invasion were independent prognostic factors. CONCLUSION In patients with p-T1aN0M0 non-small-cell lung cancer, an elevated preoperative carcinoembryonic antigen level and blood vessel or lymphatic invasion tend to affect prognosis to a greater degree than tumor size. Therefore, the efficacy of adjuvant chemotherapy for these patients should be evaluated in clinical trials.

Clinical trial of video-assisted thoracoscopic segmentectomy using infrared thoracoscopy with indocyanine green.

OBJECTIVES The maintenance of a good surgical view is mandatory in video-assisted thoracoscopic surgery (VATS). For routine segmentectomy, it is necessary to re-inflate the lung in order to identify the intersegmental line. However, such re-inflation can occasionally obstruct the surgical view. Infrared thoracoscopy (IRT) with indocyanine green (ICG) can reveal the intersegmental line based on blood flow differences, without the need for lung re-inflation. The purpose of this study was to confirm the usefulness of IRT with ICG for VATS. METHODS Between October 2008 and September 2011, 44 consecutive patients underwent segmentectomy at our institution. In 13 patients, VATS segmentectomy using IRT with ICG was employed. Informed consent was obtained from all patients. Computed tomography was performed to identify the dominant pulmonary artery supplying the target segment. The operations were performed using two ports and one mini-thoracotomy (3-6 cm). The dominant arteries were interrupted, and the intersegmental line was identified using IRT with ICG. RESULTS Identification of the intersegmental line was possible in 11 (84.6%) of the 13 patients. The average age was 70 years, and 6 of the patients were male. The mean operation time was 191 min, and the mean bleeding volume was 64 ml. The operation time and bleeding volume were similar to the values in the other 31 patients who underwent thoracotomy (167 min/115 ml, P = 0.212/0.361, respectively). No complications attributable to IRT with ICG were observed. CONCLUSIONS VATS segmentectomy using IRT with ICG allows the maintenance of a clear surgical view and identification of the intersegmental line in a high proportion of cases. Therefore, we consider this method to be useful for minimally invasive thoracic surgery.

Pulmonary rehabilitation during induction chemoradiotherapy for lung cancer improves pulmonary function

OBJECTIVE Chemoradiotherapy for non-small cell lung cancer can impair pulmonary function, particularly when it is followed by surgery. This study aimed to document the changes in respiratory function as a result of a perioperative intensive pulmonary rehabilitation program in patients with non-small cell lung cancer who underwent induction chemoradiotherapy. METHODS A total of 82 consecutive patients underwent pulmonary resection after undergoing induction chemoradiotherapy. A pulmonary rehabilitation program was started at the same time as the induction chemoradiotherapy. Standard respiratory function tests were performed before and after induction chemoradiotherapy. Treatment-related mortality and the incidence of postoperative respiratory complications were investigated. The Wilcoxon signed-rank test was used to analyze the differences in spirometric changes. RESULTS All patients underwent a pulmonary rehabilitation program for an average of 10 weeks. Significant increases were observed in forced vital capacity (+6.4%, P = .0096) and forced expiratory volume in 1 second (+10.4%, P < .0001). Diffusing capacity of the lung for carbon monoxide decreased (-14.0%, P < .0001). Patients with respiratory impairment (forced vital capacity <80% predicted or forced expiratory volume in 1 second/forced vital capacity <70%) showed significant improvements in forced vital capacity (+13.9%, P = .0025) and forced expiratory volume in 1 second (+22.5%, P < .0001). Significant increases were observed in forced vital capacity (+7.0%, P = .0042) and forced expiratory volume in 1 second (+10.8%, P = .0001) in patients with a smoking history. There was no mortality, and postoperative respiratory morbidity was 6.1%. CONCLUSIONS A pulmonary rehabilitation program for patients with non-small cell lung cancer undergoing induction chemoradiotherapy seems to improve respiratory function. It is particularly recommended for smokers and patients with respiratory impairment.

Potent effect of adenoviral vector expressing short hairpin RNA targeting ribonucleotide reductase large subunit M1 on cell viability and chemotherapeutic sensitivity to gemcitabine in non-small cell lung cancer cells

BACKGROUND Ribonucleotide reductase large subunit (RRM1) is the main enzyme responsible for synthesis of the deoxyribonucleotides used during DNA synthesis. It is also a cellular target for gemcitabine (GEM). Overexpression of RRM1 is reportedly associated with resistance to GEM and the poor prognosis for many types of malignant tumours. Aim of the present study is to establish gene therapy against RRM1-overexpressing tumours. METHOD An adenoviral vector that encoded a short hairpin siRNA targeting the RRM1 gene (Ad-shRRM1) was constructed. Two RRM1-overexpressing non-small cell lung cancer (NSCLC) lines, MAC10 and RERF-LC-MA, were used. Finally, a human tumour xenograft model in nude mice was prepared by subcutaneously implanting tumours derived from RERF-LC-MA cells. RESULTS Ad-shRRM1 effectively downregulated RRM1 mRNA and protein in both types of NSCLC cells and significantly reduced the percentage of viable cells as detected by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay (p<0.005). Caspase 3/7 analysis revealed that transfection with Ad-RRM1 increased the percentage of apoptotic cells in culture containing either type of RRM1-overexpressing cell (p<0.001). Treatment with Ad-shRRM1 exerted a potent antitumour effect against the RRM1-overexpressing RERF-LC-MA xenografts (p<0.05). Furthermore, Ad-shRRM1-mediated inhibition of RRM1 specifically increased sensitivity to gemcitabine of each type of RRM1-overexpressing tumour cell. Combination treatment with Ad-shRRM1 and GEM exerted significantly greater inhibition on cell proliferation than Ad-shRRM1 or GEM treatment alone. CONCLUSION RRM1 appeared to be a promising target for gene therapy, and Ad-shRRM1 had strong antitumour effects, specifically anti-proliferative and pro-apoptotic effects, against NSCLC cells that overexpressed RRM1. Combination therapy with Ad-shRRM1 and GEM may become a new treatment option for patients with NSCLC.

Innovative method using circulating tumor cells for prediction of the effects of induction therapy on locally advanced non-small cell lung cancer

BackgroundThe existence of circulating tumor cells (CTCs) in patients with lung cancer has been reported. The purpose of this study was to assess whether CTCs are predictive of the pathological effects of induction chemoradiotherapy for patients with non-small cell lung cancer.MethodsPatients who underwent induction chemoradiotherapy followed by surgery were compared with those who underwent surgery alone. Peripheral and pulmonary venous blood samples from the involved lobe were collected intraoperatively, and the number of CTCs was counted using the CellSearch™ system, an epithelial cell adhesion molecule-based immunomagnetic technique.ResultsOf the 9 patients who underwent induction therapy, 4 achieved pathological CR, 4 achieved major response, and 1 achieved minor response. All patients who underwent induction therapy and surgery alone were negative for CTCs in peripheral blood. In the induction therapy group, 4 patients showing pathological CR were negative for CTCs in pulmonary venous blood (pvCTCs) and 5 showing major/minor response were positive (mean, 57.8 cells). The numbers of CTCs in patients showing major/minor response were significantly higher than those in patients showing pathological CR (p = 0.012, Mann–Whitney U test). All 6 patients undergoing surgery alone were positive for pvCTCs (mean, 207.5 cells), showing a significant difference from those undergoing induction therapy (p = 0.038).ConclusionsThe existence of CTCs in pulmonary venous blood reflects pathological non-CR, and therapeutic pathological response may be predicted by pvCTC measurement.

Cribriform Subtype is an Independent Predictor of Recurrence and Survival after Adjustment for the Eighth Edition of TNM Staging System in Patients with Resected Lung Adenocarcinoma

Introduction: At present, cribriform arrangements are regarded as a pattern of acinar adenocarcinoma. However, recent studies have indicated that clinical outcomes for lung adenocarcinoma patients with cribriform subtype are unfavorable. To validate the prognostic significance of the cribriform pattern, we analyzed a series of 735 Japanese patients with resected lung adenocarcinoma, which was restaged according to the eighth edition of the TNM staging system. Methods: Tumors were classified in accordance with the 2015 WHO classification of lung carcinomas. The cribriform pattern was defined by invasive back‐to‐back fused tumor glands with poorly formed glandular spaces or invasive tumor nests of tumors cells that produce glandular lumina. Recurrence‐free probability (RFP) and overall survival (OS) was analyzed using the log‐rank test and the Cox proportional hazards model. Results: After the addition of the cribriform pattern, 54 of 90 acinar‐predominant tumors were reclassified as cribriform subtype. Five‐year RFP for patients with the cribriform subtype (51%) was lower than it was for patients with acinar and papillary subtype (81% and 80%, respectively) but was comparable to that for patients with solid subtype (48%). Five‐year OS for patients with the cribriform subtype (49%) was lower than it was for patients with acinar and papillary subtype (90% and 81%, respectively). On multivariate analysis adjusted for the eighth edition of the TNM staging system, the cribriform subtype was an independent prognostic factor of a worse RFP and OS. Conclusions: We have validated that the cribriform subtype is an independent factor of poor prognosis in patients with resected lung adenocarcinoma.

Double-barreled bronchoplasty for a carcinoid tumor with a rare variation of displaced bronchus

Bronchoplasty is a procedure that is often performed to preserve the lung parenchyma. We report the case of double-barreled bronchoplasty performed for a carcinoid tumor with a rare variation of displaced bronchus.

Spontaneous torsion of the right upper lung lobe: a case report

BackgroundPulmonary torsion is usually caused by thoracic surgery or trauma. Spontaneous pulmonary torsion caused by tumor and pleural effusion is very rare.Case presentationA 76-year-old Asian male with a chronic cough and suspected lung or pleural tumor presented with sudden dyspnea. Computed tomography showed that the right upper lung lobe contained a large tumor in the region of S1-3; the tumor had shifted to the posterior thoracic space and rotated 90° counterclockwise, potentially impeding blood flow. The patient underwent emergency right upper lobectomy for torsion of the right upper lung lobe. He recovered uneventfully and was discharged without complications.ConclusionsWe experienced a rare case of spontaneous torsion of the right upper lung lobe caused by a large tumor and massive pleural effusion.