SOX2 and PI3K Cooperate to Induce and Stabilize a Squamous-Committed Stem Cell Injury State during Lung Squamous Cell Carcinoma Pathogenesis.

Although cancers are considered stem cell diseases, mechanisms involving stem cell alterations are poorly understood. Squamous cell carcinoma (SQCC) is the second most common lung cancer, and its pathogenesis appears to hinge on changes in the stem cell behavior of basal cells in the bronchial airways. Basal cells are normally quiescent and differentiate into mucociliary epithelia. Smoking triggers a hyperproliferative response resulting in progressive premalignant epithelial changes ranging from squamous metaplasia to dysplasia. These changes can regress naturally, even with chronic smoking. However, for unknown reasons, dysplasias have higher progression rates than earlier stages. We used primary human tracheobronchial basal cells to investigate how copy number gains in SOX2 and PIK3CA at 3q26-28, which co-occur in dysplasia and are observed in 94% of SQCCs, may promote progression. We find that SOX2 cooperates with PI3K signaling, which is activated by smoking, to initiate the squamous injury response in basal cells. This response involves SOX9 repression, and, accordingly, SOX2 and PI3K signaling levels are high during dysplasia, while SOX9 is not expressed. By contrast, during regeneration of mucociliary epithelia, PI3K signaling is low and basal cells transiently enter a SOX2LoSOX9Hi state, with SOX9 promoting proliferation and preventing squamous differentiation. Transient reduction in SOX2 is necessary for ciliogenesis, although SOX2 expression later rises and drives mucinous differentiation, as SOX9 levels decline. Frequent coamplification of SOX2 and PIK3CA in dysplasia may, thus, promote progression by locking basal cells in a SOX2HiSOX9Lo state with active PI3K signaling, which sustains the squamous injury response while precluding normal mucociliary differentiation. Surprisingly, we find that, although later in invasive carcinoma SOX9 is generally expressed at low levels, its expression is higher in a subset of SQCCs with less squamous identity and worse clinical outcome. We propose that early pathogenesis of most SQCCs involves stabilization of the squamous injury state in stem cells through copy number gains at 3q, with the pro-proliferative activity of SOX9 possibly being exploited in a subset of SQCCs in later stages.

High-Pressure Carbon Monoxide and Oxygen Mixture is Effective for Lung Preservation.

(1) Background: Heme oxygenase-1 (HO-1) degrades heme and generates carbon monoxide (CO), producing various anti-inflammatory, anti-oxidative, and anti-apoptotic effects. This study aimed to confirm the effects of CO on the ischemia-reperfusion injury (IRI) of donor lungs using a high-pressure gas (HPG) preservation method. (2) Methods: Donor rat and canine lungs were preserved in a chamber filled with CO (1.5 atm) and oxygen (O2; 2 atm) and were ventilated with either CO and O2 mixture (CO/O2 group) or air (air group) immediately before storage. Rat lungs were subjected to heterotopic cervical transplantation and evaluated after reperfusion, whereas canine lungs were subjected to allogeneic transplantation and evaluated. (3) Results: Alveolar hemorrhage in the CO/O2 group was significantly milder than that in the air group. mRNA expression levels of HO-1 remained unchanged in both the groups; however, inflammatory mediator levels were significantly lower in the CO/O2 group than in the air group. The oxygenation of graft lungs was comparable between the two groups, but lactic acid level tended to be higher in the air group. (4) Conclusions: The HO-1/CO system in the HPG preservation method is effective in suppressing IRI and preserving donor lungs.

[Intraoperative Navigation System during Thoracoscopic Segmentectomy for Non-palpable Pulmonary Tumors;Infrared Thoracoscopy (IRT)-Indocyanine Green (ICG) and Intraoperative Computed Tomography(CT)-assisted Method].

OBJECTIVES: Recently, the use of video-assisted thoracoscopic surgery (VATS) segmentectomy for pulmonary malignancies has increased. For non-palpable lesions, securing a sufficient surgical margin is more likely to be uncertain. The purpose of this study was to evaluate the usefulness of our intraoperative navigation system in combination with the infrared thoracoscopy (IRT)-indocyanine green (ICG) method and intraoperative computed tomography (CT) during VATS segmentectomy for non-palpable pulmonary malignancies. METHODS: This study involved 12 consecutive patients who underwent both IRT-ICG and intraoperative CT-assisted thoracoscopic segmentectomy. Identification of the intersegmental line on the visceral pleura was visualized using IRT-ICG. The intersegmental line was marked by clipping, and intraoperative CT scan was performed under bilateral lung ventilation. The intraoperative CT images were used by the surgeons to confirm the correct anatomic segmental border and to secure a sufficient resection margin. RESULTS: A well-defined intersegmental line was observed in 83.3% of the patients. The rate of concordance between 3-dimensional (3D)-CT images reconstructed from intraoperative CT and preoperative simulation 3D-CT imaging was 91.7%. The mean surgical margin assessed on gross examination by the pathologist was 22.3 ± 4.5 mm. Complete resection was achieved in all patients using this approach. CONCLUSIONS: Imaging support including preoperative simulation, IRT-ICG and intraoperative CT enables surgeons to perform definitive VATS segmentectomy for non-palpable lesions.

[Video-assisted Thoracoscopic Segmentectomy Using Infrared Thoracoscopy with Indocyanine Green].

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 borders. However, such re-inflation can occasionally obstruct the surgical view and can lead to prolongation of operation time, particularly in the context of VATS. Infrared thoracoscopy( IRT) with indocyanine green (ICG) is a new method of evaluating lung perfusion. There are 2 methods in IRT. One is based on ICG absorption, and the other is based on ICG fluorescence. In our experience, both of them were useful for identification of segmental borders. However, the former method was superior for the clarity of images. No complications attributable to IRT with ICG were observed. IRT with ICG is based on blood flow rather than on ventilation and can thus achieve anatomical segmentectomy without lung re-inflation. This method will be especially useful for VATS segmentectomy.

[Can Pulmonary Rehabilitation during Preoperative Chemoradiotherapy for Non-small Cell Lung Cancer Improve the Respiratory Function?].

OBJECTIVE: Chemoradiotherapy for non-small cell lung cancer (NSCLC) 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 NSCLC 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 (FVC) [+6.4%, p=.0096] and forced expiratory volume in 1 second( FEV(1))[ +10.4%, p<.0001]. Diffusing capacity of the lung for carbon monoxide decreased(-14.0%, p<.0001). Patients with respiratory impairment (FVC <80% predicted or FEV(1)/FVCp<70%) showed significant improvements in FVC( +13.9%, p=.0025) and FEV(1)( +22.5%, p<.0001). Significant increases were observed in FVC( +7.0%, p=.0042) and FEV(1)( +10.8%, p<.0001) in patients with a smoking history. There was no mortality, and postoperative respiratory morbidity was 6.1%.

[Perioperative Management of Lung Cancer Patients with atrial fibrillation being treated by antiplatelet or anticoagulant therapy].

In an aging society, the high incidence of surgery for the patients with ischemic heart disease(IHD)or atrial fibrillation(Af) under antiplatelet or anticoagulant therapy is a great problem. Interruption of antiplatelet or anticoagulant oral agents in the perioperative period may increase the risk of coronary or cerebral events. We retrospectively reviewed the surgical outcomes for lung cancer patients with IHD or Af. We reviewed 135 patients with lung cancer(41~88 years;97 men) who had preoperative oral administration of antiplatelet or anticoagulant drugs for IHD or Af between 2005 and 2012 at 2 centers, and analyzed retrospectively the perioperative medications and complications. IHD, Af and vasospastic angina(VSA) were complicated in 94, 33 and 8 patients, respectively. Drugeluted and bare-metal stents had been placed in 18 and 19 patients. Oral agents were aspirin in 68 patients, ticlopidine in 10 patients, clopidogrel in 15 patients and warfarin in 25 patients. These agents were stopped 2 to 60 days before surgery. Perioperative heparinization was performed in 22 patients. Oral agents were restarted after confirmation of hemostasis and no need for further invasive treatment. The surgical procedures were lobectomy in 88 patients, segmentectomy in 19 and partial resection in 25. There were no hemorrhagic or thromboembolic complications in a perioperative period except 1 case of pulmonary hemorrhage and 1 case of cerebral infarction. No perioperative hospital death was documented. Short-term interruption of antiplatelet or anticoagulant drugs before lung cancer surgery and heparinization was acceptable from the view of perioperative outcomes.

[Mucosa-associated lymphoid tissue (MALT) lymphoma of the lung treated by surgery and rituximab; report of a case].

We report a case of mucosa-associated lymphoid tissue (MALT) lymphoma of the lung treated by surgery and rituximab. A 47-year-old man was referred to our hospital because of the lesion in the right middle lobe, which had enlarged gradually. Chest computed tomography(CT) scanning showed an infiltrative shadow of the right middle lobe. He underwent right middle lobectomy for the MALT lymphoma whose diagnosis and treatment. The tumor was pathologically diagnosed as CD20 immunostaining was positive and the adjuvant treatment by rituximab was performed.

Lung adenocarcinoma with micropapillary and solid patterns: Recurrence rate and trends.

BACKGROUND: Lung adenocarcinomas with micropapillary pattern (MP) or solid pattern (SP) have poor prognosis with frequent postoperative recurrence. However, treatment strategies for these histological subtypes have not been established. This study examined the recurrence rates and patterns in patients with these histological subtypes. METHODS: Overall, 238 patients with lung adenocarcinoma who underwent radical resection were included. According to the histological subtypes, the patients were classified into three groups: neither MP nor SP (MP-/SP-), MP (MP+), and SP (SP+). The clinical and pathological characteristics and recurrence-free survival (RFS) were examined in each group. In addition, univariate and multivariate analyses were performed to investigate the recurrence factors. The site of recurrence, PD-L1 expression, and driver mutations were examined in patients with postoperative recurrence. RESULTS: The recurrence rates were significantly higher in the MP+ and SP+ groups (p = 0.01). The RFS was significantly shorter in the MP+ and SP+ groups (p < 0.001) than in the MP-/SP- group, especially in pStage 1A (p = 0.001). The relationship between recurrence and pathologic factors was significant for pleural, lymphatic, and vascular invasion, as well as MP in univariate analysis and only for MP in multivariate analysis. Most recurrences were distant metastases in the MP+ and SP+ groups. PD-L1 was highly expressed in recurrent SP+ cases. CONCLUSIONS: Early-stage lung adenocarcinoma with MP or SP frequently has postoperative recurrence. Prevention of distant metastases is important in these patients to improve prognosis, and aggressive postoperative chemotherapy may be considered.

[Predictor of intrathoracic lymph node metastasis in peripheral non-small cell lung cancers 20 mm or less in greatest dimension].

PURPOSES: To assess the independent predictor of lymph node metastasis( LNM) in peripheral smallsized non-small cell lung cancers (NSCLCs), we conducted a clinicopathologic analysis of patients with small-sized NSCLCs with and without intrathoracic LNM. METHODS: We retrospectively studied 213 patients who had undergone surgical resection of NSCLCs 20 mm or less in diameter. Categories of patient characteristics were divided into 2 groups based on clinicopathologic features, and the incidence of LNM was compared. Univariate and multivariate analyses of factors affecting overall survival( OS) were also conducted. RESULTS: In pN1-2 group (n=19), the incidence of elevated (>5 ng/dl) of preoperative carcinoembryonic antigen (CEA) and larger tumor size (>10 mm) was significantly higher than that in pN0 group (n=194) [p=0.0004, 0.0025]. Preoperatively, 73.7% patients were diagnosed as having lower stage in N-staging. Multivariate analysis identified only pN staging as an independent prognostic factor (p=0.002). CONCLUSIONS: It is likely that preoperative CEA and tumor size are useful in selecting patients with micro-N1-2 disease among those with small-sized NSCLCs. Our results indicate that limited resection should be avoided in patients with elevated CEA or tumors more than 10 mm in size, even if preoperative radiographic findings suggest no intrathoracic LNM.

Lymphatic invasion is a cause of local recurrence after wedge resection of primary lung cancer.

OBJECTIVE: After securing a sufficient surgical margin at wedge resection and finding no pathologic evidence of residual tumor at the surgical margin, a considerable number of patients develop local recurrence. We investigated the correlation between sub-pleural lymphatic flow and local recurrence. METHODS: We retrospectively reviewed the medical records of 144 non-small cell lung cancer patients who underwent wedge resection between January 2006 and December 2014 at our institution. RESULTS: Postoperative recurrence was observed in 36 patients (25%). Of these, local recurrence was observed in 29 patients (80.5%). The proportion of all recurrence and local recurrence were significantly higher among patients with lymphatic vessel invasion (LVI) (p < 0.0001). Recurrence-free survival rate was significantly lower in patients with LVI (24.8%) than in patients without LVI (80.2%, p < 0.0001). Multivariate logistic regression analysis demonstrated LVI (odds ratio = 6.420, p = 0.0009) as a significant predictor of local recurrence. CONCLUSIONS: Intratumoral lymphatic invasion represents a major cause of local recurrence. Although we should aim for radical surgery whenever possible, when limited surgery is the only option, postoperative adjuvant treatment may need to be considered for patients showing lymphatic invasion even at an early stage.

Definitive concurrent chemoradiotherapy in a patient with stage IV non-small cell lung cancer due to cervical lymph node metastases.

In the American Society of Clinical Oncology guideline, it is mentioned that systemic therapy is a standard treatment, but there is no cure for patients with stage IV non-small cell lung cancer (NSCLC). Recent technical advances have facilitated the delivery of curative-intent radiation doses to some stage IV patients. In this report, we introduce a long-term disease-free survivor after concurrent chemoradiotherapy (CRT) and discuss considerations for this treatment. The patient was a 61-year-old woman diagnosed with stage IV adenocarcinoma of the lung classified as cT4N3M1c; the M1c classification was because of multiple synchronous pathologically proven cervical lymph node metastases (CLNM). We administered concurrent CRT to all lesions with a dose of 60 Gy in 30 fractions over 6 weeks. Concurrent chemotherapy consisted of two cycles of carboplatin and pemetrexed. Adjuvant chemotherapy was performed with five cycles of carboplatin and pemetrexed followed by three cycles of pemetrexed alone. As of 43 months after CRT, the patient was still alive without disease. In conclusion, our patient with stage IV NSCLC due to CLNM achieved long-term disease-free survival by concurrent CRT as with patients with locally advanced NSCLC. Patient subgroups should be explored to achieve long-term disease-free survival after definitive CRT in patients with stage IV NSCLC due to CLNM.

Customized Adjuvant Chemotherapy Based on Biomarker Examination May Improve Survival of Patients Completely Resected for Non-small-cell Lung Cancer.

AIM: Adjuvant platinum-based chemotherapy is recommended for patients with completely resected stage II (N1) or III (N2) non-small cell lung cancer (NSCLC). However, the optimal chemotherapy regimen is difficult to predict for individual patients. Our previous prospective study on individualized treatment according to biomarker status, such as excision repair cross-complementing 1 (ERCC1), class III ß-tubulin (tubulin), thymidylate synthase (TYMS) and ribonucleotide reductase M1 (RRM1), achieved encouraging results in patients with advanced NSCLC. The present study further examined the effect of biomarker-based adjuvant chemotherapy in patients with completely resected NSCLC. PATIENTS AND METHODS: Between January 2006 and December 2014, 66 patients with localized (stage I-IIIA) NSCLC who underwent R0 operation received 2-4 cycles of platinum doublet adjuvant chemotherapy: Platinum plus docetaxel, platinum plus pemetrexed for adenocarcinoma, and platinum plus tegafur/gimeracil/oteracil combination (TS-1) for squamous cell carcinoma (SCC) were selected according to the registered protocol at each period. Immunohistochemistry was used to evaluate the biomarkers: ERCC1 status for platinum, tubulin for docetaxel, and TYMS for pemetrexed and TS-1. A matched chemotherapy regimen meant that platinum plus docetaxel was administered in patients negative for ERCC1 and negative for tubulin, platinum plus pemetrexed in patients with adenocarcinoma positive for tubulin, negative for ERCC1 and negative for TYMS, and platinum plus TS-1 in those with SCC positive for tubulin, negative for ERCC1 and negative for TYMS. RESULTS: The 5-year survival rate was 77.5% considering all 66 patients, and 85.7%, 71.8%, and 78.8% for those with p-stage I, II, and III, respectively. Patients who received a matched chemotherapy regimen (n=13; platinum plus docetaxel in eight, platinum plus pemetrexed in five) had significantly better 5-year survival than patients with unmatched biomarker status (n=53) (100% vs. 71.0%, p=0.0011). CONCLUSION: Customized adjuvant chemotherapy based on biomarker examination significantly improved the survival of patients with NSCLC, regardless of p-stage.

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.

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.

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.

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

BACKGROUND: The 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. METHODS: Patients 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. RESULTS: Of 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). CONCLUSIONS: The existence of CTCs in pulmonary venous blood reflects pathological non-CR, and therapeutic pathological response may be predicted by pvCTC measurement.

Prognostic factors in patients after lobectomy for p-T1aN0M0 adenocarcinoma.

OBJECTIVES: The seventh edition of the TNM Classification of Malignant Tumours was published in 2009. This study was conducted to investigate the prognostic factors of p-T1aN0M0 pulmonary adenocarcinoma, which is the earliest stage defined in the new TNM classification. METHODS: We retrospectively studied 122 patients who underwent lobectomy at our institution for p-T1aN0M0 adenocarcinoma, as re-categorized in the seventh TNM classification. The patients were separated into groups on the basis of the following clinicopathologic parameters: age, < 70 vs. > 70 years; gender, male vs. female; preoperative serum carcinoembryonic antigen (CEA) level, < 5.0 vs. ≥ 5.0 ng/dl; tumour size, <10 vs. >10 mm; intratumoral vascular or lymphatic invasion, positive vs. negative. Univariate and multivariate analyses of disease-free survival were performed. RESULTS: The median follow-up period was 41.4 months. Univariate analysis showed that prognostic factors such as age, CEA elevation and intratumoral vascular or lymphatic invasion were significant (age, < 70 vs. > 70 years; 97.1% vs. 82.0%, P = 0.0027; preoperative serum CEA level, < 5.0 vs. > 5.0 ng/dl; 93.3% vs. 33.3%, P < 0.0001; intratumoral vascular or lymphatic invasion, positive vs. negative; 31.3% vs. 96.5%, P < 0.0001). Multivariate analysis demonstrated that only intratumoral vascular or lymphatic invasion was a significantly independent prognostic factor (P = 0.0039, Hazard Ratio, 0.066; 95% Confidence Interval, 0.011-0.419). CONCLUSIONS: Intratumoral vascular or lymphatic invasion should always be studied and included in the final pathology report in order to consider potential clinical and therapeutic relevance. The efficacy of adjuvant chemotherapy for these patients should also be evaluated in clinical trials.

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.

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.

Non-surgical closure of post-pneumonectomy empyema with bronchopleural fistula after open window thoracotomy using basic fibroblast growth factor.

Empyema with bronchopleural fistula (BPF) is one of the severest complications following pneumonectomy. Many papers have reported that it is difficult to cure, with a high rate of associated mortality. Closure of the fistula and an appropriate choice of obliteration materials are crucial for successful treatment. However, obliteration is sometimes impractical because of a lack of suitable materials, excessive surgical risk, or lack of patient willingness to undergo the procedure. We report a case of post-pneumonectomy empyema with BPF that was treated by non-surgical closure after open-window thoracotomy (OWT) with the use of basic fibroblast growth factor (bFGF), which was sprayed into the unepithelialized empyema cavity transiting from epidermis and surrounding the fistula. After spraying, the orifice of the OWT was covered by a film dressing. This procedure yielded successful results after two months.