Intraoperative margin assessment by wireless signals in thoracoscopic anterior (S3) segmentectomy using a radiofrequency identification marker

Despite the use of near-infrared thoracoscopy with intravenous indocyanine green, intraoperative assessment of the surgical margin for the resection of non-palpable tumors located near the intersegmental plane requires highly advanced surgical skill for the prevention of local recurrence. Because the demarcation line is limited to the pleural surface, to overcome uncertainty in tumor palpation for deeply located small-sized lesions, other supplemental localization techniques have been proposed. Here, we present a novel surgical technique using radiofrequency identification markers for intraoperative assessment of the lateral surgical margin in segmentectomy

Strategy for lung parenchyma-sparing bronchial resection: a case series report

Lung parenchyma-sparing bronchial resection is uncommon, and the operative procedure depends on the cause and location of the stenosis. We present 6 cases and discuss the different surgical strategies for sleeve resection of the central airway without lung resection. Bronchoplasty for the main bronchus and truncus intermedius was performed with a posterolateral approach. We resected the right main bronchus including the right lateral wall of the lower trachea and half of the carina obliquely and performed an anastomosis. The tumour in the left lobar bronchus was exposed and removed by transient division of the accompanying pulmonary artery. Although post-transplant stenosis and malacia can pose a challenge, bronchoplasty can be used as a definitive treatment in experienced centres

Peritumoral radiomics features on preoperative thin-slice CT images can predict the spread through air spaces of lung adenocarcinoma

The spread through air spaces (STAS) is recognized as a negative prognostic factor in patients with early-stage lung adenocarcinoma. The present study aimed to develop a machine learning model for the prediction of STAS using peritumoral radiomics features extracted from preoperative CT imaging. A total of 339 patients who underwent lobectomy or limited resection for lung adenocarcinoma were included. The patients were randomly divided (3:2) into training and test cohorts. Two prediction models were created using the training cohort: a conventional model based on the tumor consolidation/tumor (C/T) ratio and a machine learning model based on peritumoral radiomics features. The areas under the curve for the two models in the testing cohort were 0.70 and 0.76, respectively ( = 0.045). The cumulative incidence of recurrence (CIR) was significantly higher in the STAS high-risk group when using the radiomics model than that in the low-risk group (44% vs. 4% at 5 years;  = 0.002) in patients who underwent limited resection in the testing cohort. In contrast, the 5-year CIR was not significantly different among patients who underwent lobectomy (17% vs. 11%;  = 0.469). In conclusion, the machine learning model for STAS prediction based on peritumoral radiomics features performed better than the C/T ratio model

Validation Study of the International Association for the Study of Lung Cancer Histologic Grading System of Invasive Lung Adenocarcinoma

[Introduction] A histologic grading system for invasive lung adenocarcinoma (ADC) has been proposed by the International Association for the Study of Lung Cancer (IASLC) Pathology Committee in June 2020. This study evaluated the prognostic value of the IASLC histologic grading system (the IASLC system) in a large Japanese cohort. [Methods] We performed comprehensive histologic subtyping using the semiquantitative estimation of five major patterns and complex glandular patterns in patients with a completely resected lung ADC and determined the histologic grade using the IASLC system. Concordance index and receiver-operating characteristic curves were used to evaluate the clinical utility of the IASLC system for recurrence and death; the comparison was performed with the architectural-pattern system (the Arch system) and the grading system on the basis of the two most predominant patterns (the Sica’s system). [Results] Of 1002 patients with invasive ADC, 235 had recurrent disease and 166 died of lung cancer. The concordance index and area under the curve of the IASLC system were 0.777 and 0.807 for recurrence and 0.767 and 0.776 for death, respectively. These were similar to those of the Arch system (0.763 and 0.796 for recurrence, 0.743 and 0.755 for death) and the Sica’s system (0.786 and 0.814 for recurrence, 0.762 and 0.773 for death). [Conclusions] We reported that the IASLC system for invasive lung ADC has prognostic significance by evaluating a large Japanese cohort. We believe that the IASLC grading system will provide physicians with better information for postsurgery treatment

Prognostic significance of cribriform adenocarcinoma of the lung: validation analysis of 1,057 Japanese patients with resected lung adenocarcinoma and a review of the literature

Background: Cribriform-predominant adenocarcinoma of the lung (Cribri-ADC) is a recently described tumor growth pattern. However, its prognostic impact has not been clearly determined. We analyzed the data of a series of 1, 057 Japanese patients with resected lung adenocarcinoma to identify the clinical significance of Cribri-ADC. Methods: Cribriform pattern (Cribri-p) is defined as invasive back-to-back fused tumor glands with poorly formed glandular spaces or invasive tumor nests comprising tumors cells that produced glandular lumina. We investigated the correlations of Cribri-p and Cribri-ADC with clinicopathological factors as well as disease-free survival (DFS) and overall survival (OS). Results: Cribri-p was present in 217 patients (20.5%) and Cribri-ADC was determined in 25 patients (2.4%). Cribri-p was associated with larger tumor size, pleural invasion, vascular invasion, lymphatic invasion, and spreading through air spaces (STAS) (all, P<0.0001). Cribri-ADC was associated with younger age (P=0.019), vascular invasion (P=0.0025), STAS (P<0.0001), and ALK rearrangement (P=0.012). The DFS curve of patients with Cribri-ADC was identical to that of patients with solid adenocarcinoma; however, the OS curve was located between that of patients with papillary and acinar adenocarcinoma. Of the 10 patients who had tumor recurrences, eight had EGFR mutations or ALK rearrangement, six of whom achieved relatively long survival (median, 64.6, range, 37.4–113 months) following treatment with tyrosine kinase inhibitors (TKIs). In multivariate analysis, Cribri-ADC was not an independent prognostic factor of either recurrence or death. Conclusions: Cribri-ADC is associated with a higher risk of recurrence; however, most patients can be successfully treated with TKIs

Epidermal growth factor receptor (EGFR)—tyrosine kinase inhibitors as a first-line treatment for postoperative recurrent and EGFR-mutated non-small-cell lung cancer

[OBJECTIVES] To clarify survival outcomes and prognostic factors of patients receiving epidermal growth factor receptor (EGFR) - tyrosine kinase inhibitors (TKIs) as first-line treatment for postoperative recurrence. [METHODS] A retrospective chart review was performed to identify consecutive patients who received EGFR-TKIs as first-line treatment for postoperative recurrence of non-small-cell lung cancer (NSCLC) harbouring EGFR gene mutations at our institution between August 2002 and October 2020. Therapeutic response, adverse events, progression-free survival (PFS) and overall survival (OS) were investigated. Survival outcomes were assessed using the Kaplan–Meier analysis. The Cox proportional hazards model was used for univariable and multivariable analyses. [RESULTS] Sixty-four patients were included in the study. The objective response and disease control rates were 53% and 92%, respectively. Grade 3 or greater adverse events were noted in 4 (6.3%) patients, including 1 patient (1.6%) of interstitial pneumonia. The median follow-up period was 28.5 months (range 3–202 months). The total number of events was 43 for PFS and 23 for OS, respectively. The median PFS was 18 months, and the median OS was 61 months after EGFR-TKI treatment. In multivariable analysis, osimertinib showed a tendency to prolong PFS [hazard ratio (HR) 0.41, 95% confidence interval (CI) 0.12–1.1; P = 0.071], whereas the micropapillary component was significantly associated with shorter OS (HR 2.1, 95% CI 1.02–6.9; P = 0.045). [CONCLUSIONS] EGFR-TKIs as first-line treatment appeared to be a reasonable treatment option in selected patients with postoperative recurrent EGFR-mutated NSCLC. Osimertinib and the micropapillary component may be prognostic factors

MCL1 inhibition is effective against a subset of small-cell lung cancer with high MCL1 and low BCL-XL expression

There have been few advances in the treatment of small-cell lung cancer (SCLC) because of the lack of targets. MCL1, a member of the anti-apoptotic BCL-2 family, may be a treatment target in several cancers, including SCLC. However, whether the expression profile of the anti-apoptotic BCL-2 family affects MCL1 inhibition strategy is unknown. A tissue microarray (TMA) was created from consecutive patients who were diagnosed with SCLC and had previously undergone surgery at Kyoto University Hospital (Kyoto, Japan) between 2001 and 2017. We used S63845, a MCL1 inhibitor, to assess the cytotoxic capacity in SCLC cell lines including a patient-derived cell line in vitro and in vivo. The combination of S63845 with navitoclax, a double BCL-XL/BCL-2 inhibitor, was also employed to examine the comprehensive inhibition of the anti-apoptotic BCL-2 family. Immunohistochemistry of a TMA from patients with surgically resected SCLC demonstrated high MCL1 expression with low BCL-XL and BCL-2 to be the most common expression profile. S63845 was effective in high MCL1- and low BCL-XL-expressing SCLC cell lines. S63845 induced BAK-dependent apoptosis in vitro, and the anti-tumor efficacy was confirmed in an in vivo model. Although knockdown of BCL-XL and BCL-2 improved the cytotoxic activity of S63845 and its combination with navitoclax increased the anti-tumor cytotoxicity, the therapeutic range of S63845 with navitoclax was narrow in in vivo studies. Our study suggests MCL1 inhibition therapy be applied for high MCL1- and low BCL-XL-expressing SCLC patients

GEP100を伴ったHer2過剰発現は、肺腺癌の自律的浸潤能を促進し、転移のバイオマーカーとなる

京都大学0048新制・課程博士博士(医学)甲第16499号医博第3637号新制||医||990(附属図書館)29156京都大学大学院医学研究科医学専攻(主査)教授 戸井 雅和, 教授 野田 亮, 教授 武藤 誠学位規則第4条第1項該当Doctor of Medical ScienceKyoto UniversityDA

Protocol for cell-type-specific tissue reconstruction in the murine lung fibrogenic microenvironment

Summary: Pulmonary fibrosis is a process characterized by epithelial injury and fibroblast activation. It is also well recognized as a predisposition to lung cancer. Here, we present a protocol to establish an in vivo model to evaluate the dynamics of alveolar epithelial type 2 cells and lung cancer cells in the context of the lung fibrogenic microenvironment. Utilizing the cell transfer technique, we detail a basis for therapeutic approaches in pulmonary fibrosis and tools for precision medicine against lung cancer.For complete details on the use and execution of this protocol, please refer to Miyata et al. (2022).1 : Publisher’s note: Undertaking any experimental protocol requires adherence to local institutional guidelines for laboratory safety and ethics

P40 expression in small cell lung cancer: The presence of p40-positive cells does not always indicate squamous differentiation

Background: Small cell lung cancer (SCLC) is normally diagnosed with hematoxylin and eosin stains, although some cases require immunohistochemistry (IHC). P40 is highly sensitive and specific for squamous cell carcinoma and is thus considered the best marker for this cancer. However, the status of p40 expression in SCLC is not well known. The aim of this study was to analyze p40 expression in resected SCLC using IHC. Methods: Forty‐four surgically resected SCLC cases were enrolled. Clinical data were obtained from the patients’ medical records. Pathologists blinded to the patients’ clinical data reviewed the SCLC slides. IHC was performed on a representative slide of each case. Results: Although p40 was not diffusely expressed in any of the SCLC cases, p40‐positive cells were observed in the tumors in 15 cases (34.1%). Ten of these exhibited p40 in < 1% of tumor cells. In the remaining five cases, 1–5% of tumor cells expressed p40, and in three of these, the cells expressing p40 also expressed TTF‐1 and neuroendocrine markers. There was no statistically significant relationship between p40 positivity and any other clinicopathological characteristics. Conclusions: Some resected SCLCs express p40 focally. This result suggests that the presence of positive p40 cells does not exclude a diagnosis of SCLC. Thus, small biopsy or cytology specimens with p40‐positive cells must be diagnosed carefully