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Makoto Sonobe



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    P1.05 - Interventional Diagnostics/Pulmonology (Not CME Accredited Session) (ID 937)

    • Event: WCLC 2018
    • Type: Poster Viewing in the Exhibit Hall
    • Track:
    • Presentations: 1
    • Moderators:
    • Coordinates: 9/24/2018, 16:45 - 18:00, Exhibit Hall
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      P1.05-05 - Endobronchial Ultrasound-Guided Transbronchial Needle Aspiration for Suspected Malignancy; Current Status and Issues (ID 13209)

      16:45 - 18:00  |  Author(s): Makoto Sonobe

      • Abstract
      • Slides

      Background

      The number of endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) is now increasing, since it is less invasive and useful for the pathological diagnosis of lung cancer or thoracic and hilar lymph node enlargement. However, there are some problems to be solved, such as diagnostic accuracy and complications. Here, we retrospectively reviewed our experiences of EBUS-TBNA performed for diagnosis of malignant diseases.

      a9ded1e5ce5d75814730bb4caaf49419 Method

      Between July 2009 and December 2017, 489 patients underwent EBUS-TBNA. Among them, the subject of this study was 424 cases underwent EBUS-TBNA for diagnosis of malignancy. We retrospectively analyzed the completion rate, the complication rate, the adequate sample collection rate and the diagnostic accuracy of EBUS-TBNA among these 424 patients.

      4c3880bb027f159e801041b1021e88e8 Result

      Among all 424 cases, the target lesions of EBUS-TBNA consisted of mediastinal lesions (n=303), hilar lesions (n=69) and both mediastinal and hilar lesions (n=52). Almost all EBUS-TBNAs were performed under conscious anesthesia, while 9 EBUS-TBNAs were performed under general anesthesia. Among 424 cases, EBUS-TBNA was completed in 408 cases (96.2%) and the collection of adequate sample was performed in 382 cases (90.1%). There were four complications (0.94%); they consisted of mediastinal infection (n=2), obstructive pneumonia (n=1) and airway obstruction (n=1). All 4 cases were treated medically and fully recovered. Among 16 incomplete cases, 10 cases were histologically diagnosed with having malignancy; 5 cases were surgically diagnosed, and other 5 cases were diagnosed by EBUS-TBNA under general anesthesia. Other 3 cases were clinically diagnosed with having malignant diseases. Among 26 patients in whom adequate samples were not collected, 14 patients were finally diagnosed with having malignancy. On the other hand, among 382 patients in whom adequate samples were collected, the sensitivity, specificity, positive predictive value and negative predictive value were 90.0%, 100.0%, 100.0% and 76.0%, respectively. Furthermore, the diagnostic accuracy of EBUS-TBNA for hilar lesions was the least among the three lesions (mediastinal: 94.2%, hilar: 83.9%, both mediastinal and hilar: 91.8%, p=0.029).

      8eea62084ca7e541d918e823422bd82e Conclusion

      Among the patients in whom adequate samples were collected, the outcome of EBUS-TBNA was favorable. Since complications are rare but can happen, early recognition and treatment for complication are important. When EBUS-TBNA under conscious sedation is not completed, EBUS-TBNA under general anesthesia or other diagnostic approaches such as mediastinoscopy and video-assisted thoracoscopic surgery are to be considered.

      6f8b794f3246b0c1e1780bb4d4d5dc53

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    P1.16 - Treatment of Early Stage/Localized Disease (Not CME Accredited Session) (ID 948)

    • Event: WCLC 2018
    • Type: Poster Viewing in the Exhibit Hall
    • Track:
    • Presentations: 1
    • Moderators:
    • Coordinates: 9/24/2018, 16:45 - 18:00, Exhibit Hall
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      P1.16-25 - A Propensity Score Model for Appropriate Treatment Selection (Sublobar Resection vs. SBRT) In Patients With cStage I NSCLC (ID 11246)

      16:45 - 18:00  |  Author(s): Makoto Sonobe

      • Abstract
      • Slides

      Background

      Stereotactic body radiotherapy (SBRT) and sublobar resection (SLR) are current treatment options for patients with cStage I non-small-cell lung cancer (NSCLC) who are operable, but at high risk for lobectomy. However, optimal selection of the two treatments remains controversial. Purposes of this study are to identify pre-treatment factors affecting treatment decision and to evaluate their impact on outcomes.

      a9ded1e5ce5d75814730bb4caaf49419 Method

      We retrospectively reviewed patients who underwent SBRT or SLR for cStage I NSCLC because of medical comorbidity between 2003 and 2009. Patients who were with performance status of 2 or worse, those who had no data on pre-treatment pulmonary function test, or those who had no histological confirmation of NSCLC were excluded. A propensity score (PS) model of treatment decision (0 toward SBRT, and 1 toward SLR) was generated using stepwise logistic regression incorporating pre-treatment factors.

      4c3880bb027f159e801041b1021e88e8 Result

      Ninety-two and 65 patients who underwent SBRT and SLR, respectively, were enrolled into this analysis. Median potential follow-up period was 8.6 years. The following factors remained in the PS model after stepwise selection: age, sex, Charlson comorbidity index (CCI), body mass index (BMI), forced expiratory volume in 1 second (FEV1) and tumor diameter. Old age, male, CCI of 1 or more, underweight BMI and large tumor had coefficients toward SBRT (Table).

      In a cohort with PS of 0.5 or more, overall survival was significantly better in SLR patients than in SBRT patients (79.5% and 47.5% at 5 years, respectively; P = 0.004). In a cohort with PS<0.5, whereas, overall survival was similar between SLR and SBRT (43.3% and 39.7% at 5 years, respectively; P = 0.805).

      Coefficients for propensity score
      Factors Coefficients
      (Intercept) (3.95)
      Age per 10y -0.53
      Sex female 0 (ref)
      male -0.62
      CCI 0 0 (ref)
      1 -0.41
      >=2 -0.97
      BMI underweight -0.98
      normal 0 (ref)
      overweight 0.44
      FEV1 per 1L 0.84
      Tumor diameter per 1cm -0.34

      8eea62084ca7e541d918e823422bd82e Conclusion

      The PS model would help appropriate treatment selection for high-risk operable patients. Although patients with PS of 0.5 or more benefit from SLR, SBRT provides comparable outcomes for patients with PS<0.5.

      6f8b794f3246b0c1e1780bb4d4d5dc53

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    P2.03 - Biology (Not CME Accredited Session) (ID 952)

    • Event: WCLC 2018
    • Type: Poster Viewing in the Exhibit Hall
    • Track:
    • Presentations: 1
    • Moderators:
    • Coordinates: 9/25/2018, 16:45 - 18:00, Exhibit Hall
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      P2.03-29 - Prognostic Significance of Phosphorylated Fyn in Patients with Lung Adenocarcinoma (ID 12824)

      16:45 - 18:00  |  Author(s): Makoto Sonobe

      • Abstract

      Background

      Src family tyrosine kinases, including Fyn, are non-receptor tyrosine kinases and they are known to drive malignancy in various kinds of cancers. Some papers have reported that Fyn is an effector of EGFR signaling. Additionally, Fyn is recognized as an additional therapeutic target. However, little is known about the clinical importance of phosphorylated Fyn (pFyn) in lung adenocarcinoma. The purpose of the present study is to clarify the prognostic significance of pFyn in lung adenocarcinoma.

      a9ded1e5ce5d75814730bb4caaf49419 Method

      A total of 251 lung adenocarcinoma specimens were collected from patients who underwent surgery in our institute. Tissue microarrays (TMA) were assembled from paraffin-embedded tumor blocks. We analyzed pFyn expression through immunostaining of TMA and classified them as 0, +1, +2, +3. The association between pFyn expression as well as the patients’ clinical information was statistically analyzed. Correlations were compared using Pearson's chi-square test and overall survival (OS) were compared using the log-rank test after propensity score matching (age, gender, smoking history, pathological stage, EGFR mutation status, and p53 mutation status). The Institutional Review Board approved this study and informed consent for tumor tissue usage was obtained pre-operatively.

      4c3880bb027f159e801041b1021e88e8 Result

      Unadjusted pathologic stage distributions by TNM classification (WHO, 7th edition) were as follows: Stage 1A: 128 patients, Stage 1B: 73, Stage 2A: 23, Stage 2B: 4, Stage 3A: 23. pFyn was positive in 118 cases (47.6%). There was a significant correlation between pFyn expression and gender, pathological stage, p53 mutation status, and poor OS. The propensity score adjusted analysis revealed that the prognosis of pFyn positive group was significantly worse compared to the pFyn negative group (p=0.046), which was observed only in the patients with mutant EGFR.

      pfyn.png

      8eea62084ca7e541d918e823422bd82e Conclusion

      pFyn expression may affect the prognosis of patients with lung adenocarcinoma in a EGFR mutation dependent manner.

      6f8b794f3246b0c1e1780bb4d4d5dc53

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    P2.09 - Pathology (Not CME Accredited Session) (ID 958)

    • Event: WCLC 2018
    • Type: Poster Viewing in the Exhibit Hall
    • Track:
    • Presentations: 1
    • Moderators:
    • Coordinates: 9/25/2018, 16:45 - 18:00, Exhibit Hall
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      P2.09-23 - A Combination of Podoplanin and E-Cadherin Expression in Lung SqCC may be a Poor Prognostic Indicator: A Propensity Score-Matched Analysis. (ID 12889)

      16:45 - 18:00  |  Author(s): Makoto Sonobe

      • Abstract
      • Slides

      Background

      The combination of clinicopathological prognostic factors for lung squamous cell carcinoma (SqCC) has not been still advocated. The aim of this study is to analyze the combination of prognostic markers of SqCC.

      a9ded1e5ce5d75814730bb4caaf49419 Method

      Retrospective chart review was performed to identify patients undergoing resection for SqCC between 2003 and 2015 (Ethical approval #: E2235). We examined the expressions of E-cadherin, vimentin, and podoplanin in cancer cells on tissue microarray to evaluate their prognostic value. Survival outcomes were analyzed with Kaplan-Meier method and log-rank test. To eliminate selection bias, propensity score-matched analysis on the basis of clinicopathological factors was performed.

      4c3880bb027f159e801041b1021e88e8 Result

      Two hundred and two patients underwent complete resection with curative intent were identified (Median follow-up: 50.0 months, range: 0.67-150, 5y-OS: 67.5%, 5y-DFS: 53.4%). There was no significant difference in the prognosis of patients with low E-cadherin expression alone (OS: p=0.242 and DFS: p=0.401) and podoplanin-positive alone (OS: p=0.389 and DFS: p=0.874). However, OS and DFS in the combination of podoplanin-positive and low E-cadherin expression group was significantly lower than those in another group (OS; 75.0% vs 57.0%, respectively, p=0.034, DFS; 65.2% vs 44.2%, respectively, p=0.031.).

      figure_12889.tif

      8eea62084ca7e541d918e823422bd82e Conclusion

      A combination of podoplanin-positive and low E-cadherin expression in lung SqCC may be a poor prognostic indicator.

      6f8b794f3246b0c1e1780bb4d4d5dc53

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    P2.16 - Treatment of Early Stage/Localized Disease (Not CME Accredited Session) (ID 965)

    • Event: WCLC 2018
    • Type: Poster Viewing in the Exhibit Hall
    • Track:
    • Presentations: 1
    • Moderators:
    • Coordinates: 9/25/2018, 16:45 - 18:00, Exhibit Hall
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      P2.16-27 - Indocyanine Green Virtual Assisted Lung Mapping (ICG-VAL-MAP): Anyone Can Perform a Visible Preoperative Marking Successfully (ID 11299)

      16:45 - 18:00  |  Author(s): Makoto Sonobe

      • Abstract

      Background

      As a preoperative marking of small pulmonary nodules, we developed Virtual Assisted Lung Mapping (VAL-MAP), which is consisted of preoperative simulation using three-dimensional CT images and transbronchial dye marking using indigocarmine (IC). Between 2012 and 2016, we performed VAL-MAP in more than 200 cases in a single institution; however, we sometimes came across a situation, in which an identification of marked IC was difficult at post-marking CT and/or during surgery. Herein, we have developed a new VAL-MAP (ICG-VAL-MAP) using indocyanine green (ICG) and contrast agent. The purpose of this study was to prospectively evaluate the visibility of newly-developed ICG-VAL-MAP in an identification of ICG at post-marking CT and during surgery.

      a9ded1e5ce5d75814730bb4caaf49419 Method

      Since January in 2017, we have performed ICG-VAL-MAP, using ICG and contrast agent in addition to IC as a marker, in 48 patients. During surgery, fluorescence endoscope system was used for identification of marked ICG.

      4c3880bb027f159e801041b1021e88e8 Result

      Targeted lesions were 61 nodules with the diameter ranging from 2 to 38 mm (median 8 mm). The depth from the pleural surface ranged from 0 to 35 mm (median 8 mm). Total marked numbers were 122 (IC: 37, ICG: 85). At post-marked CT, IC was easily identified in 28 markings (76%), difficult to be identified in 5 (13%), unable to be identified in 4 (11%). On the other hand, ICG was easily identified in all markings. During surgery, IC was easily identified in 29 markings (78%), slightly identified in 4 (11%), unable to be identified in 4 (11%). On the other hand, ICG was easily identified in 84 markings (99%). Only in 1 case, ICG marking was accidentally placed far from a pleural surface, but ICG was slightly identified in a collapsed lung during surgery. There were no severe complications related to ICG-VAL-MAP. All nodules were diagnosed intraoperatively and an appropriate sublobar resection was performed in each patient. In all cases, surgeons were very much satisfied with ICG-VAL-MAP. In details, ICG-VAL-MAP was indispensable for resection of the targeted lesions in 17 cases (35%), and it was helpful for resecting the targeted lesion confidently in 30 cases (63%). However, only in 1 case, ICG-VL-MAP was thought to be unnecessary (2%).

      8eea62084ca7e541d918e823422bd82e Conclusion

      We confirmed that ICG-VAL-MAP was a novel and promising technique with better visibility for the complete resection of small pulmonary nodules.

      6f8b794f3246b0c1e1780bb4d4d5dc53

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    P3.09 - Pathology (Not CME Accredited Session) (ID 975)

    • Event: WCLC 2018
    • Type: Poster Viewing in the Exhibit Hall
    • Track:
    • Presentations: 1
    • Moderators:
    • Coordinates: 9/26/2018, 12:00 - 13:30, Exhibit Hall
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      P3.09-13 - Molecular Profiling Suggests the Different Mechanisms Among Local Invasiveness in Resected Human Lung Adenocarcinoma (ID 14060)

      12:00 - 13:30  |  Author(s): Makoto Sonobe

      • Abstract

      Background

      Local invasive factors are pathologically defined as pleural or lymphovascular invasion in lung cancer. Accumulating evidences have shown that these factors are associated with metastatic activity finally leading to poor survival of the patients. Here we examined the correlations of cancer-progressive molecular markers with local invasiveness in resected human adenocarcinoma.

      a9ded1e5ce5d75814730bb4caaf49419 Method

      Clinical samples were obtained from the 256 cases of lung adenocarcinoma which were consecutively operated to treat from January 2001 to December 2007 in our institution. Pathological stage distribution of the cases by TNM classification was below: 1A: 118, 1B: 71, 2A: 22, 2B: 4, 3A: 23, 3B: 1, 4:17.

      Tissue microarrays were immunohistochemically (IHC) stained. The previously published IHC data of molecular markers and DNA mutation data of EGFR and K-ras using our same cohorts were integrated. These markers included TP53, E-cadherin, vimentin, TWIST, CD133, CD44, Aldehyde dehydrogenase (ALDH), Carbonic anhydrase (CA)-9, Lactate dehydrogenase (LDH)-A, Glucose transporter (GLUT)-1, Hypoxia inducible factor (HIF) 1α, Ubiquitin C-terminal hydrolase (UCH)-L 1, Grb2, GEP100, Arf6, AMAP1, EPB41L5, phosphorylated receptor tyrosine kinases (EGFR, HER2, cMet, VEGFR2).

      Statistical analyses were performed by chi-square test or log-rank test. For survival data analyses, stage4 cases were excluded.

      4c3880bb027f159e801041b1021e88e8 Result

      Positive rates for these markers were from 9.6~63.4% as shown in the table.

      The most significant correlations with pleural, lymphatic, and vascular invasion were found in EPB41L5 (p=0.0005), LDH-A (p<0.0001), and, p53 (p<0.0001) and GLUT-1 (p<0.0001), respectively.

      The probable markers predicting both the nodal metastases and the occurrence of events were associated with EMT, glycolytic, hypoxia, and Arf6-related pathways.

      004171.jpg

      8eea62084ca7e541d918e823422bd82e Conclusion

      The pivotal markers were different among the types of local invasiveness. Pathways commonly used in local invasiveness, nodal and distant metastases were suggested to be EMT, glycolysis, hypoxia-related.

      6f8b794f3246b0c1e1780bb4d4d5dc53