Publications by authors named "Hiroaki Kuroda"

119 Publications

Novel strategy to treat lung metastases: Hybrid therapy involving surgery and radiofrequency ablation.

Thorac Cancer 2021 Jun 9. Epub 2021 Jun 9.

Department of Diagnostic and Interventional Radiology, Aichi Cancer Center Hospital, Nagoya, Japan.

Background: This study was performed to evaluate the clinical outcomes of hybrid treatment involving surgical resection and percutaneous radiofrequency ablation for patients with multiple lung metastases.

Methods: Seventeen patients (6 men, 11 women; median age, 52 years; range, 16-78 years) underwent hybrid treatment involving surgery and radiofrequency ablation to treat multiple lung metastases (median number, 4; range, 2-26) between May 2014 and February 2020. The primary lesions were colorectal carcinoma (n = 9), uterine endometrial carcinoma (n = 3), osteosarcoma (n = 2), renal cell carcinoma (n = 1), glottic carcinoma (n = 1), and fibrolamellar hepatocellular carcinoma (n = 1). Twenty-four sessions each of surgery and radiofrequency ablation were performed. Safety, disease-free survival, and overall survival were evaluated. Safety was assessed according to the Clavien-Dindo Classification.

Results: A grade IVa adverse event of empyema developed in one patient (4%, 1/24) after surgery. A grade IIIa adverse event of pneumothorax and a grade II adverse event of lung abscess occurred in four (17%, 4/24) and one session (4%, 1/24) after radiofrequency ablation, respectively. During the median follow up of 34 months (range, 8-67 months), 10 patients (59%, 10/17) developed new metastases. The 5-year disease-free survival rate was 32%. Four or fewer lung metastases (p = 0.008) and metastases from colorectal carcinoma (p = 0.02) were factors significantly associated with longer disease-free survival. One patient (6%, 1/17) died of tumor progression 29 months after initial treatment. The 5-year overall survival rate was 88%.

Conclusions: The strategy of hybrid treatment involving surgery and radiofrequency ablation may offer good outcomes for patients with multiple lung metastases.
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http://dx.doi.org/10.1111/1759-7714.14041DOI Listing
June 2021

Clinical Guideline-Guided Outcome Consistency for Surgically Resected Stage III Non-Small Cell Lung Cancer: A Retrospective Study.

Cancers (Basel) 2021 May 21;13(11). Epub 2021 May 21.

Department of Thoracic Oncology, Aichi Cancer Center, Nagoya 464-8681, Japan.

Clinical guidelines can help reduce the use of inappropriate therapeutics due to localism and individual clinician perspectives. Nevertheless, despite the intention of clinical guidelines to achieve survival benefit or desirable outcomes, they cannot ensure a robust outcome. This retrospective study aimed to investigate whether guideline-consistency, including adjuvant treatments after surgical resection (ATSR) and guideline-matched first-line treatment for recurrence (GMT-R), according to the genomic profiles and immune status, could influence overall survival (OS). From 2006 to 2017, the clinical data of 308 patients with stage III non-small cell lung cancer (NSCLC) after surgical resection were evaluated. ATSR and GMT-R were allowed in 164 (53.2%) and 129 (62.3%) patients cases after surgical pulmonary resection, among which 207 (67.2%) recurrences were identified. The 5-year OS in guideline-consistent cases was significantly better than that in guideline-inconsistent cases ( < 0.01). Subgroup analyses further showed that the 5-year OS after propensity adjustment was significantly better in guideline-consistent than in guideline-inconsistent cases ( < 0.01), but not in either ATSR or GMT-R ( = 0.24). These data suggest that the guideline-consistent alternatives, which comprise ATSR or GMT-R, can contribute to survival benefits in pathological stage III NSCLC. However, only either ATSR or GMT-R has a potential survival benefit in these patients.
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http://dx.doi.org/10.3390/cancers13112531DOI Listing
May 2021

Micropapillary Predominance Is a Risk Factor for Brain Metastasis in Resected Lung Adenocarcinoma.

Clin Lung Cancer 2021 Apr 18. Epub 2021 Apr 18.

Department of Thoracic Surgery, Aichi Cancer Center Hospital, Nagoya, Japan.

Background: Histologic subtyping offers some prognostic value in lung adenocarcinoma. We thus hypothesized that histologic subtypes may be useful for risk stratification of brain metastasis (BM). In this study, we aimed to investigate the impact of histologic subtypes on the risk for BM in patients with resected lung adenocarcinoma.

Patients And Methods: Of 1099 consecutive patients who had undergone curative-intent surgery (2000-2014), 448 patients who had undergone complete resection for lung adenocarcinoma were included in this study. Correlated clinical variables and BM-free survival were analyzed.

Results: Micropapillary predominance was significantly associated with higher risk of BM after complete resection in univariate analyses (P < .001). In addition, multivariate analyses showed that micropapillary predominance was an independent risk factor for BM (hazard ratio = 2.727; 95% confidence interval, 1.260-5.900; P = .011), along with younger age and advanced pathologic stage. Unlike the other subtypes, an increase in the percentage of the micropapillary subtype was positively correlated with an increase in BM frequency. Patients with micropapillary adenocarcinoma showed significantly poorer brain metastasis-free survival compared with those with non-micropapillary adenocarcinoma (3 years, 78.2% vs. 95.6%; 5 years, 67.3% vs. 94.3%; P < .001).

Conclusion: The current study demonstrated a significant correlation between micropapillary subtype and higher risk of BM in patients with resected lung adenocarcinoma. This routine histologic evaluation of resected adenocarcinoma may provide useful information for the clinician when considering postoperative management in patients with lung adenocarcinoma. Histologic subtyping offer some prognostic value in lung adenocarcinoma. Because brain metastasis is critical and often refractory to systemic chemotherapy, early detection is clinically important to achieve effective local treatment. We retrospectively analyzed the association between histologic subtypes and occurrence of brain metastasis and found a significant association between micropapillary predominance and higher risk for brain metastasis. Our findings may be relevant when considering postoperative management.
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http://dx.doi.org/10.1016/j.cllc.2021.04.001DOI Listing
April 2021

Robotic open-thoracotomy-view approach using vertical port placement and confronting monitor setting.

Interact Cardiovasc Thorac Surg 2021 May 11. Epub 2021 May 11.

Department of Thoracic Surgery, Aichi Cancer Center Hospital, Nagoya, Japan.

Objectives: Robotic lung resections (RLRs) are conventionally performed using look-up views of the thorax from the caudal side. To conduct RLR with views similar to those in open thoracotomy, we adopted a vertical port placement and confronting upside-down monitor setting, which we called robotic 'open-thoracotomy-view approach'. We herein present our experience of this procedure.

Methods: We retrospectively reviewed 58 patients who underwent RLR (43 with lobectomy; 15 with segmentectomy) with 3-arm open-thoracotomy-view approach using the da Vinci Surgical System between February 2019 and October 2020. The patient cart was rolled in from the left cranial side of the patient regardless of the side to be operated on. Robotic ports were vertically placed along the axillary line, and 2 confronting monitors and 2 assistants were positioned on each side of the patient. The right-side monitor, which was set up for the left-side assistant to view, projected the upside-down image of the console surgeon's view.

Results: All procedures were safely performed. The median duration of surgery and console operation was 215 and 164 min, respectively. Emergency conversion into thoracotomy and severe morbidities did not occur, and the median postoperative hospitalization duration was 3 days. In all procedures, the console surgeon and 2 assistants had direct 'bird-eye' views of the cranially located intrathoracic structures and instrument tips, which are sometimes undetectable with the conventional look-up view.

Conclusions: The open-thoracotomy-view approach setting is a possible option for RLR. It offers natural thoracotomy views and can circumvent some of the known limitations of the conventional procedure.
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http://dx.doi.org/10.1093/icvts/ivab033DOI Listing
May 2021

Differential diagnosis among benign endobronchial papillary tumors with a glandular component.

Pathol Res Pract 2021 Jun 28;222:153457. Epub 2021 Apr 28.

Department of Thoracic Surgery, Aichi Cancer Center Hospital, Nagoya, Japan.

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http://dx.doi.org/10.1016/j.prp.2021.153457DOI Listing
June 2021

Survival benefits of salvage surgery for primary lung cancer based on routine clinical practice.

Thorac Cancer 2021 Jun 4;12(11):1716-1720. Epub 2021 May 4.

Department of Thoracic Surgery, Mie Chuo Medical Center, Tsu, Japan.

Background: Premeditated induction chemotherapy followed by surgical resection is accepted as safe and effective. Studies on salvage surgery in patients with incompletely cured lung cancer are lacking. This study aimed to demonstrate the safety and efficacy of salvage surgery.

Methods: We conducted a retrospective multi-institutional cohort study on patients who underwent salvage surgery for advanced (stage III and IV) non-small cell lung cancer (NSCLC) between January 2005 and December 2016 at the 14 hospitals of the Chubu Lung Cancer Surgery Study Group. A total of 37 patients were assigned to the salvage surgery group; a lobectomy with mediastinal lymph node dissection was performed. The survival benefit was assessed using the Kaplan-Meier method and the Cox proportional hazard model.

Results: Although postoperative complications were observed in 11 patients (29.7%), surgery-related death occurred in only one patient (mortality rate: 2.7%) resulting from respiratory failure caused by interstitial pneumonia exacerbation. Postoperative recurrence was observed in 22 patients (61.1%), the incidence of brain metastasis being high (nine patients: 40.9%). The five-year survival rate from the first day of treatment was 60%. The survival of the postoperative pathological stage (s'-stage) I group was significantly better (five-year survival rate: 80.9%) than that of the other groups (p < 0.05). S'-stage was the most significant factor (p < 0.01) associated with long-term survival.

Conclusions: Salvage surgery is a feasible therapeutic modality for advanced lung cancer. Downstaging to s'-stage I with previous treatment was most important for survival. Complete resection (R0) should be the goal because surgical procedures were tolerated despite intense treatment.
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http://dx.doi.org/10.1111/1759-7714.13961DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8169288PMC
June 2021

Sarcopenia is poor risk for unfavorable short- and long-term outcomes in stage I non-small cell lung cancer.

Ann Transl Med 2021 Feb;9(4):325

Department of Thoracic Surgery, Aichi Cancer Center Hospital, Nagoya, Aichi, Japan.

Background: Sarcopenia characterized by skeletal muscle loss may influence postoperative outcomes through physical decline and weakened immunity. We aimed to investigate clinical significance of sarcopenia in resected early-stage non-small cell lung cancer (NSCLC).

Methods: We retrospectively reviewed 315 consecutive patients with pathologic stage I NSCLC who had undergone lobectomy with systematic nodal dissection. Sarcopenia was defined as the lowest quartile of psoas muscle area on the 3rd vertebra on the high-resolution computed tomography (HRCT) image. Clinicopathological variables were used to investigate the correlation to postoperative complications as well as overall and recurrence-free survival.

Results: Upon multivariable analysis, male sex [odds ratio (OR) =5.780, 95% confidence interval (CI): 2.681-12.500, P<0.001], and sarcopenia (OR =21.00, 95% CI: 10.30-42.80, P<0.001) were independently associated with postoperative complications. The sarcopenia group showed significantly lower 5-over all survival (84.4% 69.1%, P<0.001) and recurrence-free survival (77.2% 62.0%, P<0.001) comparing with the non-sarcopenia group. In a multivariable analysis, sarcopenia was an independent prognostic factor [hazard ratio (HR) =1.978, 95% CI: 1.177-3.326, P=0.010] together with age ≥70 years (HR =1.956, 95% CI: 1.141-3.351, P=0.015) and non-adenocarcinoma histology (HR =1.958, 95% CI: 1.159-3.301, P=0.016).

Conclusions: This is the first study which demonstrates that preoperative sarcopenia is significantly associated with unfavorable postoperative complications as well as long-term survival in pathologic stage I NSCLC. This readily available factor on HRCT may provide valuable information to consider possible choice of surgical procedure and perioperative management.
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http://dx.doi.org/10.21037/atm-20-4380DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7944314PMC
February 2021

Weak-evidence Fusion Candidates Detected by a FusionPlex Assay Using the Ion Torrent System.

In Vivo 2021 Mar-Apr;35(2):993-998

Department of Thoracic Oncology, Aichi Cancer Center, Nagoya, Japan.

Background/aim: The Archer FusionPlex platform is widely used for comprehensive fusion-gene detection in cancer tissues. This platform separately displays results for strong-evidence and weak-evidence fusion candidates (WEFCs). Distinctive fusion patterns are frequently found in the weak-evidence category and information about the patterns is clinically essential.

Patients And Methods: We describe the type and frequency of WEFCs observed using the FusionPlex Sarcoma Panel (S Panel) and the FusionPlex ALK, RET, and ROS1 ver2 Panel (ARR Panel).

Results: A total of 97 specimens were examined and 620 candidates were detected and categorized as WEFCs. A median of five WEFCs were detected per sample. In the S Panel group, there were 13 WEFCs with a frequency of more than 1%. In the ARR Panel group, a total of 16 WEFCs were detected with a frequency of more than 1%.

Conclusion: Specific WEFCs were detected according to the panel selected.
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http://dx.doi.org/10.21873/invivo.12342DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8045057PMC
December 2020

Subsegmental resection preserves regional pulmonary function: A focus on thoracoscopy.

Thorac Cancer 2021 04 14;12(7):1033-1040. Epub 2021 Feb 14.

Department of Surgery, Division of Thoracic Surgery, The Teikyo University, Tokyo, Japan.

Background: The aim of this study was to evaluate regional postoperative preserved pulmonary function (PPPF) and three-dimensional (3D) volumetric changes according to the number of resected subsegments and investigate the factors that most affected pre-/post PPPF.

Methods: Patients who underwent thoracoscopic lobectomy (n = 73), and segmentectomy (n = 87) were eligible for inclusion in the study. They were classified according to the number of resected subsegments which ranged from 1 to 10. The percentage of pre-/postoperative forced expiratory volume in 1 s (FEV1) was used for comparison. Furthermore, lung volumetric changes were calculated using 3D computed tomography (CT) volumetry.

Results: The percentage of pre-/postoperative EFV1 between 4 and 5-7 and between 5-7 and 10 were significant (p = 0.03 and p < 0.01, respectively), but not between 1-2 to 4 (p = 0.99). The difference between volumetric changes in the left lower lobe of patients with a number of resected subsegments was significant (p < 0.01). On univariate and multivariate analyses, chronic inflammation was significant for decrease in recovery percentages. When the PPPF was compared among resected subsegments, it gradually decreased with an increase in the number of patients without a postoperative procrastination of inflammation (p < 0.01).

Conclusions: Segmentectomy is feasible and useful for PPPF. Even a relatively large-volume resection procedure where 5-7 subsegments are resected can preserve pulmonary function. Chronic inflammation was statistically identified as a risk factor for postoperative preserved pulmonary function.

Key Points: .
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http://dx.doi.org/10.1111/1759-7714.13841DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8017248PMC
April 2021

Radiological imaging and pathological findings of small lung adenocarcinoma: a narrative review.

J Thorac Dis 2021 Jan;13(1):366-371

Department of Pathology, National Cancer Center Hospital, Tokyo, Japan.

The eighth edition of the Lung Cancer Handling Regulations defines the pathological findings of "invasion" in the pathological diagnosis of lung adenocarcinoma and terms it as adenocarcinoma in situ/minimally invasive carcinoma. In addition, the invasion diameter (tumor diameter excluding the lepidic growth region) was adopted as the pT factor, and the classification further reflected prognosis (degree of invasion/progression). Meanwhile, computed tomography imaging-based classification, where the consolidation (nodule) diameter excluding the ground glass shadow area was defined as cT, and the classification reflected the pathological invasion diameter. It is clear that the revision of the eighth edition has reduced discrepancies in the pathological findings of lung adenocarcinoma in CT imaging and assessment of the degree of invasion and progression. At the same time, the 8th edition is not yet accurate enough. Therefore, we will discuss imaging techniques to better predict the extent of adenocarcinoma invasion and progression, based on our own findings and the literature.
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http://dx.doi.org/10.21037/jtd-20-844DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7867796PMC
January 2021

Prospective study of recurrence at the surgical margin after wedge resection of pulmonary metastases.

Gen Thorac Cardiovasc Surg 2021 Jun 3;69(6):950-959. Epub 2021 Jan 3.

Department of Thoracic Surgery, National Defense Medical College, Saitama, Japan.

Background: Pulmonary metastasectomy is a common treatment for selected patients with pulmonary metastases. Among pulmonary resections, wedge resection is considered sufficient for pulmonary metastases. However, a major problem with wedge resection is the risk of local recurrence, especially at the surgical margin. The aim of this prospective study was to explore the frequency of and the risk factors for recurrence at the surgical margin in patients who underwent wedge resection for pulmonary metastases.

Methods: Between September 2013 and March 2018, 177 patients (220 lesions) with pulmonary metastases from 15 institutions were enrolled. We studied 130 cases (169 lesions) to determine the frequency of and risk factors associated with recurrence at the surgical margin in patients who underwent wedge resection. Moreover, we evaluated the recurrence-free rate and disease-free survival after wedge resection.

Results: A total of 81 (62.3%) patients developed recurrence. Recurrence at the surgical margin was observed in 11 of 130 (8.5%) cases. The 5-year recurrence-free rate was 89.1%. Per patient, multivariable analysis revealed that the presence of multiple pulmonary metastases was a significant risk factor for recurrence. Per tumor, distance from the surgical margin and tumor/margin ratio were risk factors for local recurrence. The 5-year disease-free survival rate was 34.7%, and the presence of multiple pulmonary metastases and small surgical margin were risk factors for disease-free survival by univariable analysis.

Conclusions: Among patients who undergo wedge resection for pulmonary metastasis, patients with multiple pulmonary metastases tend to develop recurrence at the surgical margin.
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http://dx.doi.org/10.1007/s11748-020-01560-7DOI Listing
June 2021

Comparison of surgical outcomes between thoracoscopic anatomical sublobar resection including and excluding subsegmentectomy.

Gen Thorac Cardiovasc Surg 2021 May 2;69(5):850-858. Epub 2021 Jan 2.

Department of Thoracic Surgery, Aichi Cancer Center, 1-1 Kanokoden Chikusa-ku, Nagoya, 464-8681, Japan.

Objectives: Despite the ubiquitous utilization of anatomical sublobar resection for malignant lung tumors, the effectiveness and feasibility of subsegmentectomy remains unclear. This study therefore compared the perioperative outcomes between anatomical sublobar resection including (IS) and excluding (ES) subsegmentectomy.

Methods: Patients who had undergone anatomical sublobar resection at our institution from January 2013 to March 2019 were retrospectively reviewed. Clinicopathologic characteristics and perioperative outcomes of the IS group (n = 58) were then analyzed the compared to those of the ES group (n = 203).

Results: No statistically significant differences in age, sex, comorbidities, tumor location, preoperative pulmonary function, or tumor size on imaging were found between both groups. The IS group had significantly higher preoperative computed tomography-guided marking rates (40% vs. 18%; p < 0.01) and used significantly more staplers for intersegmental dissection than the ES group [4, interquartile range (IQR): 3-4 vs. 3, IQR: 3-4; p = 0.03]. Both groups had comparable 30-day mortality (0% vs. 0%; p > 0.99), intraoperative complications (7% vs. 10%; p = 0.61), and postoperative complications (5% vs. 8%; p = 0.58). After propensity score matching, the IS group experienced significantly lesser blood loss than the ES group (5 mL, IQR: 1-10 vs. 5 mL, IQR: 5-20; p = 0.03). Both groups experienced no local recurrence and demonstrated similar postoperative pulmonary functions after surgery.

Conclusions: IS may be a feasible and acceptable therapeutic option for malignant lung tumors. Nonetheless, future investigations are required to further validate the current findings.
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http://dx.doi.org/10.1007/s11748-020-01556-3DOI Listing
May 2021

How preserved regional pulmonary function after thoracoscopic segmentectomy in clinical stage I non-small cell lung cancers in right upper lobe.

Gen Thorac Cardiovasc Surg 2021 Jun 2;69(6):960-966. Epub 2021 Jan 2.

Department of Thoracic Surgery, Medical Hospital, The Tokyo Medical and Dental University, Tokyo, Japan.

Objective: To investigate the efficacy of regional respiratory preservation after pulmonary resection for clinical stage I non-small cell lung cancer (NSCLC) in right upper lobe.

Methods: This retrospective study analysed patients with clinical stage I NSCLC who underwent open thoracotomy lobectomy (OTL, n = 45), thoracoscopic lobectomy (TSL, n = 137), and thoracoscopic segmentectomy (TSS, n = 37) in right upper lobe. The forced vital capacity (FVC) and forced expiratory volume in 1 s (FEV1) were examined at 3 and 6-12 months after the operation. The pre- and post-operative lung volumes were evaluated by three-dimensional reconstructed computed tomography. The rates of post- and pre-operative FVC, FEV1, and lung volumes were compared amongst the three groups.

Results: Significant differences were found in both FVC and FEV1 at 6-12 months between TSL and OTL (p < 0.01 and p = 0.02, respectively). The respiratory recovery rates of FVC and FEV1 at 6-12 months were significantly higher in TSS (98.6% ± 1.52% and 96.5% ± 1.66%) than in TSL (93.4% ± 0.79% and 90.4% ± 0.86%) (FVC: p < 0.01 and FEV1: p < 0.01). The volumetric changes were greater in TSL than in TSS for the right middle lobe (19.6% ± 2.39% and 9.59% ± 4.66%; p = 0.06) and right lower lobe (48.3% ± 2.84% and 27.9% ± 5.47%; p < 0.01) CONCLUSION: TSS might be superior to TSL or OTL depending on the moderate expansion of the remaining right lobes.
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http://dx.doi.org/10.1007/s11748-020-01561-6DOI Listing
June 2021

Selection of Pathological N0 (pN0) in Clinical IA (cIA) Lung Adenocarcinoma by Imaging Findings of the Main Tumor.

Ann Thorac Cardiovasc Surg 2020 Dec 18. Epub 2020 Dec 18.

Department of Surgery, Teikyo University Hospital, Tokyo, Japan.

Objectives: We would like to clarify the imaging findings of the main tumor that may omit the requirement for lymph node dissection in clinical IA (cIA) lung adenocarcinoma.

Methods: A total of 336 patients with cIA lung adenocarcinomas with normal preoperative carcinoembryonic antigen (CEA) who underwent surgical resection were analyzed. We investigated the association between various computed tomography (CT) imaging findings or the maximum standardized uptake value (SUVmax) of fluorodeoxyglucose-position emission tomography (FDG-PET) and lymph node metastasis. The maximum tumor diameter was calculated from the CT images using both the lung window setting (LD) and mediastinal window setting (MD). The diameter of the solid component (CD) was defined as consolidation diameter in lung window setting. The solid component ratio (C/T) was defined as CD/LD.

Results: SUVmax, MD, and C/T were independent factors related to lymph node metastasis, but CD was not (p = 0.38). The conditions required for the positive predictive value (PPV) to reach 100% were 10.6 mm for MD, 12.5 mm for CD, and 0.55 for C/T. SUVmax did not reach 100%.

Conclusions: In cIA lung adenocarcinoma with CEA in the normal range, we found that it may be possible for lymph node dissection to be omitted by MD, CD, and C/T.
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http://dx.doi.org/10.5761/atcs.oa.20-00240DOI Listing
December 2020

Clinical adjustability of radiological tools in patients with surgically resected cT1N0-staged non-small-cell lung cancer from the long-term survival evaluation.

J Thorac Dis 2020 Nov;12(11):6655-6662

Department of Thoracic Surgery, Aichi Cancer Center Hospital, Nagoya, Japan.

Background: Various radiological tools have been introduced to determine the malignancy or prognosis of lung carcinomas. We retrospectively summarized the clinical outcomes to evaluate whether radiological tools such as consolidation-to-tumor ratio (CTR), tumor disappearance ratio (TDR), and mediastinal diameter (MD) are suitable for surgically resected non-small-cell lung cancer (NSCLC).

Methods: This retrospective study included 260 patients (128 men and 132 women; median age, 64 years) with cT1N0-staged NSCLC who underwent thoracotomy. Disease-free survival (DFS) and overall survival (OS) outcomes were analyzed using the Kaplan-Meier method and Cox proportional hazards model.

Results: When the adjusted hazard ratios (HRs) with reference to cT1a/1 mi were calculated, significant differences were observed in cT1b and cT1c for DFS (P=0.04 and P<0.01, respectively) and in cT1c for OS (P=0.01). For HRs with reference to CTR (≤0.5), a significant difference was only observed in CTR (>0.5) for DFS (P=0.01). For HRs with reference to TDR (≤25%), significant differences were observed in TDR (>75%) for DFS (P=0.02) and OS (P=0.02). For HRs with reference to MD (≤5 mm), significant differences were observed in 6-20 mm (P=0.04) and >20 mm (P=0.02) for DFS and in >20 mm (P=0.02) for OS.

Conclusions: All radiological tools revealed significant correlations with prognosis in the patients with cT1N0-staged NSCLCs. We recommend the use of MD in a clinical context. However, further investigation of this issue is needed.
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http://dx.doi.org/10.21037/jtd-20-1610DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7711385PMC
November 2020

Efficacy of Xenon Light With Indocyanine Green for Intersegmental Visibility in Thoracoscopic Segmentectomy.

J Surg Res 2021 03 3;259:39-46. Epub 2020 Dec 3.

Department of Thoracic Surgery, Aichi Cancer Center Hospital, Nagoya, Japan. Electronic address:

Background: We previously reported useful methods that can be implemented to identify intersegmental boundary lines (IBLs) by using an intravenous indocyanine green (ICG) fluorescence imaging system (ICG-FS) during a thoracoscopic anatomical segmentectomy (TAS). The aim of this study was to evaluate the recently released third-generation ICG-FS that features an emphasizing xenon-light source for IBL identification.

Methods: We prospectively studied cases involving 106 consecutive patients who underwent TAS. Intraoperatively, we used the third-generation ICG-FS, the conventional ICG methods (CIM) emphasizing xenon-light (CIM-X), and the spectra-A method (SAM) emphasizing xenon-light (SAM-X), for IBL identification. Furthermore, 16 of the 106 patients (15%) could be simultaneously evaluated using old-generation ICG-FSs, CIM, and SAM. All images were completely quantified for illuminance and for three colors, red, green, and blue.

Results: IBLs were successfully identified in all the patients (100%) with no adverse events. The SAM-X significantly increased the illuminance, especially in the resecting segments, compared to the CIM (39.0 versus 22.2, P < 0.01) and SAM (39.0 versus 29.3, P < 0.01), with enhanced red color compared to the CIM (33.1 versus 21.9, P < 0.01) and SAM (33.1 versus 14.0, P < 0.01). Furthermore, the SAM-X significantly increased the illuminance contrast compared to the CIM-X (34.1 versus 15.3, P < 0.01).

Conclusions: The present study suggests that the SAM-X potentially provided images with the highest visibility and colorfulness compared to the older generation ICG-FSs or CIM-X. Secure IBL identification can be more easily and safely performed using the SAM-X.
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http://dx.doi.org/10.1016/j.jss.2020.11.028DOI Listing
March 2021

Comparison of Surgical Outcomes Between Invasive Mucinous and Non-Mucinous Lung Adenocarcinoma.

Ann Thorac Surg 2020 Nov 23. Epub 2020 Nov 23.

Department of Pathology and Molecular Diagnostics, Aichi Cancer Center, Nagoya, Japan.

Background: Invasive mucinous adenocarcinoma (IMA) is a rare subtype of invasive lung adenocarcinoma. However, the clinical course and prognostic outcomes following IMA resection, particularly postoperative recurrence, remain unclear.

Methods: We pathologically reevaluated 1362 lung adenocarcinoma resections performed at our institution, categorizing cases into the IMA group (72 cases) and non-IMA group (1290 cases). The IMA group was further classified into pneumonia and nodular types based on preoperative computed tomography.

Results: Overall, the IMA group had lower carcinoembryonic antigen levels (3 vs. 8 ng/mL; p < .01), fewer lymph node metastasis (4% vs. 24%; p < .01), and more KRAS mutations (56% vs. 7%; p < .01) than the non-IMA group. Although postoperative recurrence rates did not differ between both groups (32% vs. 27%; p = 0.35), lung recurrence occurred more frequently in the IMA group (83% vs. 17%; p < .01). Propensity score-matched pair analysis showed that the IMA group had fewer lymph node metastasis (3% vs. 35%; p < .01), more KRAS mutations (56% vs. 9%; p < .01), and higher intrapulmonary recurrence rate (84% vs. 31%; p < .01) than the non-IMA group. The 5-year overall survival rates did not differ between both groups (74% vs. 81%; p = 0.26). However, among patients with intrapulmonary recurrence, those in the IMA group had significantly worse prognosis than those in the non-IMA group (35% vs. 77%; p < .01).

Conclusions: Intrapulmonary recurrence, which induced significantly worse prognosis, was more likely to occur in the IMA than non-IMA group.
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http://dx.doi.org/10.1016/j.athoracsur.2020.09.042DOI Listing
November 2020

The cranial-side parietal pleura pick-up method and the edge closure technique as a closure method for open thoracotomy.

J Thorac Dis 2020 Sep;12(9):5053-5055

Department of Thoracic Surgery, Aichi Cancer Center Hospital, Nagoya, Japan.

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http://dx.doi.org/10.21037/jtd-20-1212DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7578462PMC
September 2020

The impact of same-day chest drain removal on pulmonary function after thoracoscopic lobectomy.

Gen Thorac Cardiovasc Surg 2021 Apr 29;69(4):690-696. Epub 2020 Oct 29.

Department of Thoracic Surgery, Aichi Cancer Center Hospital, 1-1 Kanokoden, Chikusa-ku, Nagoya, 464-8681, Japan.

Objectives: This study aims to assess the feasibility and impact on long-term pulmonary function of chest drain removal on the operation day following thoracoscopic right upper lobectomy for clinical stage I non-small cell lung cancer.

Methods: We retrospectively evaluated the data of 116 patients between May 2013 and March 2019. We evaluated the correlations of clinical parameters of chest drain removal and medium- and long-term pulmonary function by comparing removal on operation day (R group) and retainment (D group).

Results: The R group comprised 64 patients, and the D group had 52 patients. Fifty patients (96.2%) in the D group had chest drain removed within 3 postoperative days. Since February 2016, chest drain removal on operation day was performed in 64 of 74 patients (86.5%) according to our chest drain removal protocol. Removal of chest drains on operation day was associated with shorter postoperative hospitalization (p < 0.01) and lower postoperative complications ≧ grade II of the Clavien-Dindo classification (p = 0.026). Only one patient in the R group needed reinsertion. The R group had greater spirometry results at 3- and 12-postoperative months (POM). R group patients had statistically improved pulmonary functions from 3 to 12POM, while those in the D Group were stagnated at 6POM.

Conclusions: Removal of chest drains on operation day using our protocol is safe and feasible for thoracoscopic right upper lobectomy. This protocol was statistically associated with slightly better long-term pulmonary function, which could not bring clinically meaningful medium- and long-term benefit.
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http://dx.doi.org/10.1007/s11748-020-01516-xDOI Listing
April 2021

Four Hours Postoperative Mobilization is Feasible After Thoracoscopic Anatomical Pulmonary Resection.

World J Surg 2021 Feb 23;45(2):631-637. Epub 2020 Oct 23.

Department of Thoracic Surgery, Aichi Cancer Center Hospital, 1-1 Kanokoden, Chikusa-ku, Nagoya, 464-8681, Japan.

Background: We aimed to analyze the feasibility and risk factors associated with early mobilization (EM) within 4 h after thoracoscopic lobectomy and segmentectomy.

Methods: This study retrospectively evaluated 214 consecutive patients who underwent thoracoscopic anatomical pulmonary resection using our EM protocol between October 2017 and February 2019. We compared the correlations of the patients' characteristics including the total number of drugs and perioperative parameters such as air leak, and orthostatic hypotension (OH) between the EM (E group) and failed EM (F group) groups. Second, we evaluated risk factors for OH, which often causes critical complications.

Results: A total of 198 patients (92.5%: E group) completed the EM protocol, whereas 16 patients did not (7.5%: F group). The primary causes of failure were severe pain, air leak, postoperative nausea and vomiting, and OH (n = 1, 3, 8, and 4). Upon univariate analysis, air leakage, OH, and non-hypertension were identified as risk factors for failed EM (all p <0.05). EM was associated with a shortened chest tube drainage period (p <0.01). Thirty patients (14%) experienced OH, and 20% of them failed EM. A total number of drugs ≥5 (p = 0.015) was an independent risk factor for OH. Operative and anesthetic variables were not associated with EM or OH.

Conclusions: The EM protocol was safe and useful for tubeless management. Surgeons should be advised to actively prevent air leak. Our EM protocol achieved a low frequency of OH in mobilization. Due to its versatility, our mobilization protocol may be promising, especially in patients without severe comorbidities. Clinical registration number: The study protocol was approved by the Review Board of Aichi Cancer Center (approval number: 2020-1-067).
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http://dx.doi.org/10.1007/s00268-020-05836-0DOI Listing
February 2021

AKT1 Mutations in Peripheral Bronchiolar Papilloma: Glandular Papilloma and Mixed Squamous Cell and Glandular Papilloma Is Distinct From Bronchiolar Adenoma.

Am J Surg Pathol 2021 01;45(1):119-126

Departments of Pathology and Molecular Diagnostics.

Glandular papilloma (GP) and mixed squamous cell and glandular papilloma (MP) are rare benign pulmonary tumors occurring in the bronchi. Bronchiolar adenoma (BA) was recently characterized as a pulmonary tumor exhibiting alveolar spread. Both GP/MP and BA are composed of a mixture of glandular, ciliated, squamous, and basal cells. We aimed to clarify whether GP/MP and BA represent the same tumor. We evaluated the detailed histologic characteristics of 11 cases involving pulmonary peripheral tumors that exhibited histologic features of GP/MP or BA, and performed genetic analyses using targeted panel sequencing, allele-specific polymerase chain reaction, and digital polymerase chain reaction. Histologically, 4 and 7 tumors were classified as GP/MP and BA, respectively. GP/MP showed endobronchiolar papillary growth with a pseudostratified or stratified epithelium. In contrast, 5 BAs showed a predominant flat structure with a bilayered or pseudostratified epithelium, whereas 2 BAs showed a GP/MP-like papillary architecture. The mean epithelial thickness in each tumor was significantly larger in GP/MPs and BAs with a GP/MP-like morphology (103 to 242 μm) than in flat-predominant BA (23 to 47 μm, P=0.0010). AKT1 E17K mutations were detected in all GP/MPs and BAs with GP/MP-like morphology but were absent in the 5 flat-predominant BAs. AKT1 mutations were always concurrent with BRAF or HRAS mutations, and the variant allele frequency or percentage of mutant copies of AKT1 mutations was equal to those of BRAF or HRAS mutations. GP/MPs are characterized by AKT1 mutations concurrent with BRAF or HRAS mutations. Peribronchiolar papillary tumors with AKT1 mutations may also be classified as GP/MP.
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http://dx.doi.org/10.1097/PAS.0000000000001573DOI Listing
January 2021

Efficacy of local therapy for oligoprogressive disease after programmed cell death 1 blockade in advanced non-small cell lung cancer.

Cancer Sci 2020 Dec 31;111(12):4442-4452. Epub 2020 Oct 31.

Department of Thoracic Oncology, Aichi Cancer Center Hospital, Nagoya, Japan.

Immune checkpoint inhibitors (ICIs) have dramatically changed the strategy used to treat patients with non-small-cell lung cancer (NSCLC); however, the vast majority of patients eventually develop progressive disease (PD) and acquire resistance to ICIs. Some patients experience oligoprogressive disease. Few retrospective studies have evaluated clinical efficacy in patients with oligometastatic progression who received local therapy after ICI treatment. We conducted a retrospective analysis of advanced NSCLC patients who received PD-1 inhibitor monotherapy with nivolumab or pembrolizumab to evaluate the effects of ICIs on the patterns of progression and the efficacy of local therapy for oligoprogressive disease. Of the 307 patients treated with ICIs, 148 were evaluated in our study; 42 were treated with pembrolizumab, and 106 were treated with nivolumab. Thirty-eight patients showed oligoprogression. Male sex, a lack of driver mutations, and smoking history were significantly correlated with the risk of oligoprogression. Primary lesions were most frequently detected at oligoprogression sites (15 patients), and 6 patients experienced abdominal lymph node (LN) oligoprogression. Four patients showed evidence of new abdominal LN oligometastases. There was no significant difference in overall survival (OS) between the local therapy group and the switch therapy group (reached vs. not reached, P = .456). We summarized clinical data on the response of oligoprogressive NSCLC to ICI therapy. The results may help to elucidate the causes of ICI resistance and indicate that the use of local therapy as the initial treatment in this setting is feasible treatment option.
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http://dx.doi.org/10.1111/cas.14605DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7734009PMC
December 2020

Primary pneumonectomy, pneumonectomy after induction therapy, and salvage pneumonectomy: a comparison of surgical and prognostic outcomes.

J Thorac Dis 2020 May;12(5):2672-2682

Department of Thoracic Surgery, Aichi Cancer Center Hospital, Nagoya, Japan.

Background: Surgical outcomes of pneumonectomy for lung cancer differ based on various therapeutic strategies.

Methods: One hundred and fifty-one patients who underwent pneumonectomy were divided into three groups based on patients' therapeutic conditions: a primary pneumonectomy group (no preoperative treatment, n=137), an induction group (planned surgery after induction chemotherapy or chemoradiotherapy, n=10), and a salvage group (surgery for residual or enlarged lesions after radical non-operative therapies, n=4).

Results: Multivariate analysis showed that completeness of resection (P=0.003), subcategorization of whether there was no invasion, infiltration only to the main bronchus or pleura, or invasion of other deeper structures (P=0.008), and the presence or absence of mediastinal lymph node metastasis (P=0.033) were significant prognostic factors. Severe postoperative complications occurred in 5.1% (7/137), 20% (2/10), and 0% (0/4) in the primary pneumonectomy, induction, and salvage groups, respectively. Among patients with pN0-1 disease, the 3-year overall survival rate was 58.7% in the primary pneumonectomy group, 100% and 40% in cases with high and low pathological effects in the induction group, respectively, and 50% in the salvage group. Among patients with pN2 disease, this rate was 41.4% in the primary pneumonectomy group, and no patients survived for postoperative 2 years in the other groups.

Conclusions: For patients undergoing pneumonectomy, subcategorization based on the invasion status (none/bronchus/pleura or other deeper structures) is a crucial prognostic factor. To consider pneumonectomy in the induction or salvage setting, selecting patients with pN0-1 disease may be mandatory.
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http://dx.doi.org/10.21037/jtd.2020.03.19DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7330390PMC
May 2020

Comparison of radiopaque dye materials for localization of pulmonary nodules before video-assisted thoracic surgery.

J Thorac Dis 2020 May;12(5):2070-2076

Department of Diagnostic and Interventional Radiology, Aichi Cancer Center, Nagoya, Aichi, Japan.

Background: Although a mixture of pigments and radiopaque materials was reported to be useful material for lung nodule localization, the optimal combination has not been well investigated. The purpose of this study is to evaluate the characteristics of various combinations of pigments and radiopaque materials for localization of pulmonary nodules prior to video-assisted thoracic surgery (VATS).

Methods: We compared stability, viscosity, and visibility of 6 radiopaque dye materials of (I) mixture of indigo carmine and lipiodol; (II) mixture of indigo carmine, lipiodol, and lidocaine gel; (III) mixture of indocyanine green in water solution (w-ICG) and lipiodol; (IV) mixture of w-ICG, lipiodol, and lidocaine gel; (V) ICG in contrast medium solution (cm-ICG); and (VI) mixture of cm-ICG and lidocaine gel. Stability was evaluated by observing changes in the mixtures in the test tube with time visually and radiographically. Viscosities were measured by rotational viscometer. Materials were injected into an expanded pig-lung phantom, and area on CT and visibility on thoracoscopy camera were evaluated.

Results: Separation could be seen 15 min after preparation in (I) and (III), and 1 h after preparation in (II), both visually and radiographically. In (IV), separation could be seen on the photographs but not on the X-ray images from 3 h after preparation. (V) and (VI) showed no changes within the 2-day observation period. The viscosities of the materials were (I) 0.2±0.1, (II) 2.9±0.1, (III) 0.2±0.1, (IV) 2.6±0.1, (V) 0.2±0.1, and (VI) 1.2±0.1 dPa·s. The area on CT showed very strong negative correlation with viscosity (r=-0.97). The injection point of each material was easily detected on thoracoscopy camera.

Conclusions: Radiopaque dye materials appear useful for localizing pulmonary nodules before VATS; their diffusion in the lung parenchyma can be suppressed by using materials of high viscosity.
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http://dx.doi.org/10.21037/jtd-19-4057DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7330362PMC
May 2020

Sublobar resection versus lobectomy for patients with resectable stage I non-small cell lung cancer with idiopathic pulmonary fibrosis: a phase III study evaluating survival (JCOG1708, SURPRISE).

Jpn J Clin Oncol 2020 Sep;50(9):1076-1079

Department of Surgical Oncology, Hiroshima University Hospital, Hiroshima, Japan.

The standard treatment for the patients with surgically resectable early non-small cell lung cancer (NSCLC) is lung lobectomy. However, if patients have idiopathic pulmonary fibrosis combined with early stage lung cancer, there is no standard treatment for this population. Patients with idiopathic pulmonary fibrosis have chronic progressive decline in respiratory function; thus, the preservation of respiratory function is essential. The aim of this trial is to confirm the clinical effectiveness of sublobar resection such as wedge resection or segmentectomy for early NSCLC with idiopathic pulmonary fibrosis compared with lobectomy in a randomized phase III trial. The primary endpoint is overall survival. If the non-inferiority of overall survival and minimal invasiveness are proven, it can be a new standard treatment for early NSCLC with idiopathic pulmonary fibrosis. A planned total 430 patients will be enrolled from 50 institutions over 5 years. This trial has been registered in the UMIN Clinical Trials Registry with code UMIN000032696 [http://www.umin.ac.jp/ctr/index.htm].
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http://dx.doi.org/10.1093/jjco/hyaa092DOI Listing
September 2020

Targeted RNA sequencing with touch imprint cytology samples for non-small cell lung cancer patients.

Thorac Cancer 2020 07 5;11(7):1827-1834. Epub 2020 May 5.

Department of Thoracic Surgery, Tokyo Medical and Dental University, Tokyo, Japan.

Background: RNA-based sequencing is considered ideal for detecting pathogenic fusion-genes compared to DNA-based assays and provides valuable information about the relative expression of driver genes. However, RNA from formalin-fixed paraffin-embedded tissue has issues with both quantity and quality, making RNA-based sequencing difficult in clinical practice. Analyzing stamp-derived RNA with next-generation sequencing (NGS) can address the above-mentioned obstacles. In this study, we validated the analytical specifications and clinical performance of our custom panel for RNA-based assays on the Ion Torrent platform.

Methods: To evaluate our custom RNA lung panel, we first examined the gene sequences of RNA derived from 35 NSCLC tissues with diverse backgrounds by conventional methods and NGS. Next, we moved to the clinical phase, where clinical samples (all stamp-derived RNA) were used to examine variants. In the clinical phase we conducted an NGS analysis while simultaneously applying conventional approaches to assess the feasibility and validity of the panel in clinical practice.

Results: In the prerun phase, all of the variants confirmed with conventional methods were detected by NGS. In the clinical phase, a total of 80 patients were enrolled and 80 tumor specimens were sequenced from February 2018 to December 2018. There were 66 cases in which the RNA concentration was too low to be measured, but sequencing was successful in the vast majority of cases. The concordance between NGS and conventional methods was 95.0%.

Conclusions: RNA extraction using stamp specimens and panel sequencing by NGS were considered applicable in clinical settings.

Key Points: Significant findings of the study Next-generation sequencing using RNA from stamp specimens was able to detect driver gene changes in non-small cell lung cancer including fusion genes with the same accuracy as conventional methods. What this study adds Using RNA from stamp specimens obtained from biopsy increases the number of candidate cases for RNA sequencing in clinical settings.
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http://dx.doi.org/10.1111/1759-7714.13460DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7327906PMC
July 2020

Efficacy of Immune Checkpoint Inhibitor Monotherapy for Advanced Non-Small-Cell Lung Cancer with Rearrangement.

Int J Mol Sci 2020 Apr 9;21(7). Epub 2020 Apr 9.

Department of Thoracic Oncology, Aichi Cancer Center Hospital, 1-1 Kanokoden, Chikusa-ku, Nagoya, Aichi 464-8681, Japan.

Programmed death-ligand 1 (PD-L1) expression is a predictor of immune checkpoint inhibitor (ICI) treatment efficacy. The clinical efficacy of ICIs for non-small-cell lung cancer (NSCLC) patients harboring major mutations, such as or mutations, is limited. We genotyped 190 patients with advanced lung adenocarcinomas who received nivolumab or pembrolizumab monotherapy, and examined the efficacy in NSCLC patients with or without major mutations. Among the patients enrolled in the genotyping study, 47 patients harbored mutations, 25 patients had mutations, 5 patients had a mutation, 6 patients had a mutation, and 7 patients had rearrangement. The status of PD-L1 expression was evaluated in 151 patients, and the rate of high PD-L1 expression (≥50%) was significantly higher in patients with mutations. The progression-free survival was 0.6 (95% CI: 0.2-2.1) months for -positive patients and 1.8 (95% CI: 1.2-2.1) months for -positive patients. All patients with rearrangement showed disease progression within three months from the initiation of anti-PD-1 treatment. Our data suggested that ICI treatment was significantly less efficacious in patients with rearrangement than in patients with mutations, and PD-L1 expression was not a critical biomarker for ICI treatment for patients with one of these mutations.
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http://dx.doi.org/10.3390/ijms21072623DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7178012PMC
April 2020

Is skeletal muscle mass an optimal marker for postoperative outcomes in lung cancer patients?

J Thorac Dis 2019 Dec;11(12):5643-5645

Department of Thoracic Surgery, Aichi Cancer Center Hospital, Nagoya, Japan.

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http://dx.doi.org/10.21037/jtd.2019.11.21DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6988079PMC
December 2019

Negative reactions of BRAF mutation-specific immunohistochemistry to non-V600E mutations of BRAF.

Pathol Int 2020 May 23;70(5):253-261. Epub 2020 Jan 23.

Department of Pathology and Molecular Diagnostics, Aichi Cancer Center Hospital, Aichi, Japan.

BRAF mutations are rare driver mutations in non-small cell lung cancer (NSCLC), accounting for 1%-2% of the driver mutations, and the mutation spectrum has a wide range in contrast to other tumors. While V600E is a dominant mutation in melanoma, more than half of the mutations in NSCLCs are non-V600E. However, treatment with dabrafenib plus trametinib targets the BRAF V600E mutation exclusively. Therefore, distinguishing between V600E and non-V600E mutations is crucial for biomarker testing in NSCLC in order to determine treatment of choice. Immunohistochemistry (IHC) using the BRAF V600E mutation-specific antibody is clinically used in melanoma patients, but little is known about its application in NSCLC, particularly with regard to the assay performance for non-V600E mutations. In the present study, we examined 117 tumors with BRAF mutations, including 30 with non-V600E mutations, using BRAF mutation-specific IHC. None of the tumors with non-V600E mutations, including two compound mutations, showed a positive reaction. Furthermore, all V600E mutations were positive except for one case with combined BRAF V600E and K601_W604 deletion. Our findings confirmed that the BRAF V600E mutation-specific IHC is specific without any cross-reactions to non-V600E mutations, suggesting that this assay can be a useful screening tool in clinical practice.
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http://dx.doi.org/10.1111/pin.12903DOI Listing
May 2020