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H. Inoue



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    P1.06 - Poster Session 1 - Prognostic and Predictive Biomarkers (ID 161)

    • Event: WCLC 2013
    • Type: Poster Session
    • Track: Biology
    • Presentations: 1
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      P1.06-008 - Expression of PTRF/Cavin-1 is associated with poor prognosis of lung adenocarcinoma (ID 933)

      09:30 - 09:30  |  Author(s): H. Inoue

      • Abstract

      Background
      Polymerase I and transcript release factor (PTRF)/Cavin-1 was initially　identified as a regulator of rRNA transcription in the nucleus. It then was demonstrated to be essential to the formation of mature caveolae at the plasma membrane. Recently, downregulation of PTRF/Cavin-1 was reported in several types of cancers including non-small cell lung cancer compared to normal tissue. However, its precise expression pattern and clinical significance in lung adenocarcinoma remains unclear.

      Methods
      Proteomic analysis of 12 lung adenocarcinomas and the paired non-cancer lung tissue were preformed using iTRAQ coupled LC-MS/MS. To determine the expression pattern of PTRF/Cavin-1, we then performed immunohistochemical staining of PTRF/Cavin-1 on 186 adenocarcinoma tissues completely resected at Osaka City University Hospital from January 2005 to December 2008. To evaluate the clinical significance of PTRF/Cavin-1, the relationship between PTRF/Cavin-1 expression and clinicopathological parameters was analyzed.

      Results
      Proteomic analysis shows that expression level of PTRF/Cavin-1 is significantly lower in the cancer compared to the paired non-cancer lung tissue. This result suggests that PTRF/Cavin-1 may be involved in the development of lung adenocarcinoma. Immunohistochemistry analysis reveals that 30 cases (16%) were strongly positive for PTRF/Cavin-1 as observed in the non-cancer lung tissues, while 158 cases (84%) were negative. Furthermore, we found that overall survival rate of PTRF/Cavin-1-positve cases was significantly lower than that of negative cases (Log-rank test, p=0.0010). These findings imply that PTRF/Cavin-1 in cancer cells may facilitate the progression of lung adenocarcinoma progression.

      Conclusion
      These findings indicate that expression of PTRF/Cavin-1 in adenocarcinoma is associated with poor prognosis and might be a useful prognostic marker for lung adenocarcinomas.

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    P1.07 - Poster Session 1 - Surgery (ID 184)

    • Event: WCLC 2013
    • Type: Poster Session
    • Track: Surgery
    • Presentations: 1
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      P1.07-011 - Examination of the relevance of prolonged pulmonary fistula after pulmonary resection for lung cancer and factors about delayed wound healing (ID 1205)

      09:30 - 09:30  |  Author(s): H. Inoue

      • Abstract

      Background
      Prolonged pulmonary fistula is a common complication in pulmonary resection, which happens in 8% to 26% in patients undergoing routine pulmonary resection. And its management is difficult in many cases. Air leakages are associated with prolonged hospital stays, infectious, cardiopulmonary complications, and reoperation occasionally despite of the progress of the recent conservative cure. Blood coagulation factor XIII (BCF XIII) is known to play a role in wound healing. However little is known about the role of BCF XIII in the field of thoracic surgery. BCF XIII is known to fasciculate closure of fistula in gastro-intestine surgery. This time, we examine the relationship for prolonged air leakage and BCF XIII diabetes, chronic obstructive pulmonary disease (COPD), and total protein amount of postoperative.

      Methods
      In 32 patients who underwent pulmonary resection for lung cancer at Bell-land general hospital or Osaka city university hospital and experienced air leakage for at least 2 days after operation. Pre-operative HbA1c and BCF XIII and pulmonary function measured within 2 weeks pre-operatively .Post-operative total protein (TP) and BCF XIII measured at 5 days post-operatively. We evaluated the relationship between BCF XIII or HbA1c or TP or COPD and duration of chest drain placement respectively.For statistical analysis, t-test was used

      Results
      Six patients experienced a decrease in factor XIII to 70% or under normal range that was indication for administration of BCF XIII. The mean duration of chest drain placement was 5.2± 2.8 days in patients with post-operative BCF XIII level of ≥71% compared to 8.3 ± 2.8 days in those with post-operative BCF XIII level of ≤70%. Patients with post-operative BCF XIII level of ≤70% required drain placement for a significantly longer period (p<0.05). In this analysis, we did not recognize significant difference in other factors (HbA1c≦6.5% group and HbA1c≧6.6% group, Post operative TP ≧6.6 g/dl group and TP ≦6.5 g/dl , forced expiratory volume 1.0%(FEV1.0%)≧70% group and FEV1.0%＜70% group).

      Conclusion
      Factor XIII promotes crosslink of fibrin in the early stages of wound healing. Thus, factor XIII is considered to be consumed for lesion repair. In this study, we were considered the possibility BCF XIII is related to lung healing fistula. In diabetic patients, the occurrence of delayed wound healing has been reported frequently. No significant difference was noted between diabetic and non-diabetic patients in this study. We continue to increase the study case in the future, we want to evaluate the relationship between BCF XIII, diabetes or nutrition and the drainage period.

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    P2.07 - Poster Session 2 - Surgery (ID 190)

    • Event: WCLC 2013
    • Type: Poster Session
    • Track: Surgery
    • Presentations: 1
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      P2.07-017 - Pulmonary Resection for Lung Cancer Patients with Cerebrovascular and Cardiovascular Comorbidities (ID 1509)

      09:30 - 09:30  |  Author(s): H. Inoue

      • Abstract

      Background
      Patients with cerebro- and cardio-vascular comorbidities (CCVC) who undergo surgery represent a high-risk group and require careful perioperative management. In the present study, we aimed to retrospectively analyze the postoperative complications (POC) of patients with CCVC who had undergone pulmonary resection for lung cancer. Patients with cerebro- and cardio-vascular comorbidities (CCVC) who undergo surgery represent a high-risk group and require careful perioperative management. In the present study, we aimed to retrospectively analyze the postoperative complications (POC) of patients with CCVC who had undergone pulmonary resection for lung cancer.

      Methods
      Among 288 patients who underwent pulmonary resection at our institution from January 2009 to December 2011, we examined the records of 51 patients with CCVC (17.7%) to identify the risk factors for developing POC. Among the analyzed patients, we noted the presence of 34 POC, including tachyarrhythmia in 9, prolonged pulmonary fistula in 9, pyothorax in 2, cerebral infarction in 2, requirement of long-term oxygen therapy in 2, interstitial pneumonia in 2, delirium in 2, and other POC in 4. Several patients had multiple POC.

      Results
      We examined 43 male patients (84.3%); the median age was 72 years and the median preoperative forced expired volume in 1s (FEV~1~) was 2200 mL (range, 1120–3420). The patients with CCVC included 12 with cerebral infarction, 2 with transient cerebral ischemic attacks, 2 with cerebral hemorrhage, 1 with subarachnoid hemorrhage, 4 with cerebral aneurysm, 10 with arrhythmia, 17 with ischemic heart disease, 1 with valvular heart disease, 8 with aortic aneurysm/dissection, 11 with peripheral arterial disease, and 1 with a left atrial myxoma; several of these patients had multiple CCVC. Moreover, 2 patients underwent pneumonectomy, 37 underwent lobectomy, 3 underwent segmentectomy, and 9 underwent wedge resection. Postoperative morbidity rates were 21.4% in cerebrovascular comorbidity patients (p = 0.015), 53.5% in the cardiovascular comorbidity patients (p < 0.0001), 71.4% in CCVC patients (p = 0.0028), and 12.3% in patients without CCVC. No operative or in-hospital mortality was noted. Gender, age, smoking status, and smoking index were not found to be significantly related to the incidence of POC. However, patients with an FEV~1~ < 2200 mL were found to be significantly more likely to develop POC (p = 0.036).

      Conclusion
      We noted that patients with CCVC and low FEV~1 ~were more likely to develop POC.

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    P2.24 - Poster Session 2 - Supportive Care (ID 157)

    • Event: WCLC 2013
    • Type: Poster Session
    • Track: Supportive Care
    • Presentations: 1
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      P2.24-014 - Primary Lung Cancer Coexisting with Lung Metastases from Other Malignancies (ID 1080)

      09:30 - 09:30  |  Author(s): H. Inoue

      • Abstract

      Background
      Various tumors metastasize to the lung and they are often detected as multiple nodules. Regardless of recent advances in computed tomography for detecting small pulmonary nodules and ground-glass opacity components which indicate possible primary lung cancer, preoperative differential diagnosis of either metastatic or primary lung cancer is usually difficult.

      Methods
      Four cases of such multiple lung metastases that coexisted with primary lung cancer were retrospectively examined: in three of the cases (case 1 is a myxoid liposarcoma in the right thigh, case 2 is a colon cancer, and case 3 is a renal cell carcinoma), a pulmonary metastasectomy revealed that one of the tumors was primary lung cancer. In case 4, the patient had a proven lung cancer that was combined with small nodules in the ipsilateral lung, one of which was pathologically diagnosed as a metastasis from rectal cancer.

      Results
      In case 1, the patient was diagnosed with clinical stage IA primary lung cancer (a well differentiated adenocarcinoma in the left lower lobe), and a left lower lobectomy was performed 17 days after the initial surgery. In case 2, a postoperative pathological examination revealed that one of the resected pulmonary tumors in the left upper lobe, measuring 5 mm in diameter, was Noguchi type B bronchioloalveolar carcinoma. In case 3, two nodules in the right lower lobe increased in size. An intra-operative pathological examination revealed that one of the pulmonary tumors in segment S9 measuring 7 mm in diameter was adenocarcinoma, and the other tumor in segment S8 located deeply near the pulmonary artery. Subsequently, a right lower lobectomy was performed. A postoperative pathological examination revealed that the tumor in segment S9 was Noguchi type A bronchioloalveolar carcinoma, and the other tumor measuring 8 mm in segment S8 of the resected lobe was metastatic clear cell carcinoma from renal cell carcinoma. In cases 2 and 3, the patients were diagnosed with clinical stage IA primary lung cancer and no additional treatment for lung cancer was required. In case 4, the patient, who had a history of rectal cancer, underwent left upper lobectomy with mediastinal lymph node dissection, combined with partial resection of the left lower lobe. A postoperative pathological examination using immunohistological staining revealed that the nodule in the left lower lobe and a hilar lymph node were metastasis from lung cancer (pT4N1M0, stage IIIA). The remaining nodule besides the tumor in the left upper lobe was diagnosed as metastasis from rectal cancer. The patient recovered uneventfully and was discharged with a treatment plan involving postoperative chemotherapy for lung cancer.

      Conclusion
      Possible coexistence of primary lung cancer should be considered in multiple metastases from other organs. On the other hand, the stage of the lung cancer depends on a definitive tissue diagnosis of the coexisting small nodules, and the importance of active tissue diagnosis including surgery should therefore be emphasized, especially in patients with previous malignancies.

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    P3.12 - Poster Session 3 - NSCLC Early Stage (ID 206)

    • Event: WCLC 2013
    • Type: Poster Session
    • Track: Medical Oncology
    • Presentations: 1
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      P3.12-005 - Clinical Significance of preoperative arterial blood gas in patients with stage I non-small cell lung cancer (ID 1391)

      09:30 - 09:30  |  Author(s): H. Inoue

      • Abstract

      Background
      Surgical treatment is the most efficient therapy for early non-small cell lung cancer (NSCLC). For surgical treatment, oncological and physiological indications may be considered. For physiological indication, cardiopulmonary function evaluation, such as a general respiratory function test, arterial-blood-gas (ABG) analysis, an electrocardiogram, and echocardiogram are important to be determined. In ABG analysis, PaCO2>45 Torr and hypoxemia (< 90% of SaO2) have been reported as risk factors of complications after surgery. This study aimed to establish the clinical significance of preoperative ABG analysis in patients with stage I NSCLC in aspect of long-term risk.

      Methods
      The study involved 253 patients (154 male, 99 female; median age 68 years) who underwent lobectomy/bilobectomy with radical mediastinal lymph node dissection in patients with stage I NSCLC in our institution between January 1998 and December 2008. One hundred and seventy six patients had adenocarcinoma, 68 had squamous cell carcinoma, five had large cell carcinoma, and four had adenosquamous carcinoma. On pathologic staging, 129 patients were in stage IA, and 124 in stage IB. Predicted postoperative values of FEV~1~ and DLCO less than 40% is defined as high risk in pulmonary function tests. Concerning ABG parameters, the normal range for 1) PaO2 is over 75 Torr, 2) PaCO2 is 36-45 Torr and 3) pH is 7.36-7.45. The patients were divided into two groups according to ABG analysis: normal ABG group (n=167) and abnormal ABG group (n=86). The abnormal ABG group includes those whose 1)PaO2 is less than 75Torr (n=39, median 73, range, 63-74.9), 2)PaCO2 is less than 36 Torr (n=21, median 35.4, range, 32.7-35.9) or over 45 Torr (n=33, median 46.2, range, 45.0-50.6) and 3)PH is less than 7.36 (n=5, median 7.338, range, 7.332-7.356) or over 7.45 (n=8, median 7.454, range, 7.451-7.463).

      Results
      There were no significant differences in gender, performance status, Hugh-Jones classification, pathological stage, tumor histology, tumor location, surgical procedure, blood loss, operative time, and postoperative complications between the two groups. The age of patients in the normal ABG group (mean 68 years old) was significantly lower than those in the abnormal ABG group (mean 71 years old, p = 0.026). The mean follow-up period for the entire study population was 5.8 years (range 123-5201 days). No operative death occurred. The 3-, 5-, and 10-year survival rates in the normal and abnormal ABG groups were 87%, 76%, and 62%, and 78%, 64%, and 42%, respectively (p = 0.029). A log-rank test using physiological factors revealed that gender, age (>70 years old), performance status (0-1 vs 2), Hugh-Jones classification (1-2 vs 3), postoperative prediction pulmonary function test, and ABG were associated with a significant survival rate. By multivariate analysis, age, gender, and ABG (risk ratio, 4.03) were independent prognostic factors.

      Conclusion
      Preoperative ABG was a prognostic marker for stage I NSCLC. We should consider surgical strategies for patients with abnormal ABG analysis not only for immediate or short-term risk, which refers to perioperative morbidity and mortality, but also long-term survival risk.