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Background: Microscopic vascular invasion (MVI) in patients with non-small cell lung cancer (NSCLC) has been reported to be a strong predictor of poor outcomes but it has not been a descriptor of the TNM classification. The purposes of this study were to determine whether the presence of MVI is related to a predictor of poor outcomes and to explore the degree of MVI according to tumor size.Methods: A total of 1,884 patients with stage pT1-4N0-2 NSCLC who underwent complete resection comprised the study sample. Overall survival (OS) and recurrence-free proportion were estimated using the Kaplan-Meier method. The Cox proportional hazards model was used to assess independent predictors of poor outcomes.Results: Of 1,884 patients, 1,097 (58.2%) had MVI. Multivariate analysis showed MVI was a significant independent predictor of unfavorable OS (hazard ratio, 1.666; P < .001) and recurrence (hazard ratio, 2.268; P < .001). The frequency of MVI varied according to tumor size, and in each cohort of tumor sizes ≤ 2 cm, > 2 to 3 cm, and > 3 to 5 cm, there were significant differences in survival outcome by MVI status. The proportions of patients with a 5-year recurrence-free period with tumor sizes ≤ 2 cm, > 2 to 3 cm, and > 3 to 5 cm between MVI (+) and MVI (-) were 93.0% and 72.5% (P < .001), 90.8% and 63.3% (P < .001), and 86.4% and 59.9% (P < .001), respectively.Conclusions: This study demonstrated that MVI was a strong predictor of poor outcomes and that the effect is more prominent in patients with tumor sizes ≤ 5 cm. Further analysis of survival and MVI should be collected for future revision of the TNM system. [ABSTRACT FROM AUTHOR]

Malignant pleural mesothelioma ( MPM) is thought to arise from the mesothelial cells that line the pleural cavities. Most patients initially experience the insidious onset of chest pain or shortness of breath and have a history of asbestos exposure. MPM rarely presents as spontaneous pneumothorax. We report two male patients who presented with a spontaneous hydropneumothorax. One was exposed to asbestos and the other was not. Computed tomography showed tiny nodules with pleural thickness. They both underwent pleural effusion cytology and/or pleural biopsy. Therefore, the pathological diagnosis of MPM was obtained in both cases. We also reviewed 16 Japanese MPM cases with pneumothorax including our two patients. More than half of the patients suffered from pneumothorax repeatedly. We emphasize the need to obtain a pathological diagnosis of pleural effusion cytology and/or pleural biopsy in older patients presenting with a spontaneous hydropneumothorax. [ABSTRACT FROM AUTHOR]

The purpose of this study was to investigate the associated factors of insulation failure (IF) in reusable endoscopic instruments. The insulation coating of reusable endoscopic instruments underwent routine visual checks, hand washing to remove visible stains, and mechanized sterilization. We recorded the cleaning number and usage period of all instruments. The instruments were tested for IF using a detector. IF was found in eight of 69 devices (11.6%). Examining by clinical specialty, we found IF in 4 of 28 gastrointestinal (14.3%), 3 of 20 gynecological (15.0%), 1 of 12 urological (8.3%), and none of the nine thoracic devices. The median distance from the tip to the damaged part was 5 cm (3–5 cm). In the IF and the intact groups, the period of use [7 years (6–8) versus 7 years (4–8), P = 0.90] and the number of cleanings [281 (261–323) versus 261 (179–320), P = 0.27] were not significantly different. The IF group included products of three different companies; however, six of the eight (75.0%) were from the same company. Cleaning methods and usage period have a lower impact on IF. The use of reusable forceps as a monopolar device was found to pose a higher risk, requiring regular assessments. [ABSTRACT FROM AUTHOR]

Abstract: Background: We investigated blood vessel invasion (BVI) as a possible negative prognostic factor in patients with stage I non-small cell lung cancer (NSCLC) according to the 7th edition of the TNM classification. Methods: Between 1999 and 2007, a total of 694 consecutive patients with pathological stage I NSCLC underwent complete resection with systematic lymph node dissection at Tokyo Medical University Hospital. All sections of the specimens were stained by Elastica van Gieson to visualize elastic fibers and were examined to determine the prognostic symptoms of BVI. We statistically analyzed the association between BVI and clinicopathologic factors, as well as clinical outcomes. Results: BVI was detected in 201 patients with stage I NSCLC (29.0%). The 5-year overall survival (OS) rates of the non-BVI and BVI patients were 90.5% and 66.0%, respectively (p <0.0001). BVI was found to be a significant independent prognostic factor by multivariate survival analysis in stage IA and stage IB NSCLC (HR 2.591, p <0.001; HR 2.347, p =0.009, respectively). The 5-year OS rate of patients with BVI was significantly worse than that of patients without BVI in the T1a (94.5% vs 87.5%, p <0.0001), T1b (82.7% vs 65.9%, p <0.0001), and T2a (90.9% vs 61.8%, p <0.0001) subgroups. Conclusion: We identified the presence of BVI as an independent poor prognostic factor in patients with stage I NSCLC. In the future revision of the TNM staging system, the routine use of elastic fiber stains in pathological evaluations of lung cancer for BVI determination might be recommended, and tumors with BVI should be upstaged to the higher current T staging. [Copyright &y& Elsevier]

The article discusses research which investigated the clinicopathologic factors influencing postrecurrence survival (PRS) in and the effect of postrecurrence therapy (PRT) on patients with completely resected stage I non-small cell lung cancer (NSCLC). The standard of care considered for early stage NSCLC is surgical resection with a curative intent. Findings revealed that PRT, female sex and differentiation have significant association with favorable PRS.

The article discusses research which compared the number of metastatic lymph nodes (LNs) category and classic pathologic LNs category on survival in patients with completely resected non-small cell lung cancer (NSCLC). The patients included in the study underwent complete resection involving dissection of the hilar and mediastinal LNs. Findings revealed that the total number of LNs was an independent prognostic factor for overall survival and disease-free survival.

As a result of increased use of CT in both screening and daily practice, the number of early lung cancers has increased enormously. Surgeons pursue both curativity and reduced invasiveness in treating patients with early stage lung cancer; therefore, minimally invasive operations, such as video-assisted thoracoscopic surgery ( VATS) lobectomy are now being routinely performed. Most previous reports have shown that there is no difference in mortality and local recurrence between open surgery and VATS in stage I patients. However, surgeons' improved technical experience and patients' demands could soon make VATS lobectomy the operative method of choice for early stage lung cancer. Moreover, the indications for VATS are expanding to encompass complex procedures such as segmentectomy or sleeve resection. Training and dissemination of the technique and the monitoring of outcomes are necessary. [ABSTRACT FROM AUTHOR]

Abstract: Background: In this study, we investigated visceral pleural invasion (VPI) as a poor prognostic factor in patients with non-small cell lung cancer (NSCLC) according to the 7th edition of the TNM classification. Methods: Between January 2000 and December 2007, 886 consecutive patients with pathological T1a–T2b NSCLC underwent complete resection with systematic lymph node dissection in Tokyo Medical University. We statistically analyzed the association between VPI and clinicopathologic factors, or clinical outcomes. Results: The 5-year overall survival (OS) rates of the pl0, pl1, and pl2 patients were 80.8%, 63.7%, and 49.6%, respectively, with significant differences between pl0 and pl1 (p =0.002), pl1 and pl2 (p =0.03). Thus, the pl1 and pl2 patient groups were defined as patients with VPI. VPI was found to be a significant independent prognostic factor by multivariate survival analysis (p =0.0002). In patients with tumors ≤3cm, especially with tumors ≤2cm, VPI was significantly associated with an increased rate of lymph node metastasis, compared with non-VPI (p =0.0003 and p =0.015, respectively). Analysis of the OS of patients stratified by tumor size (≤3cm, 3.1–5cm, 5.1–7cm) and VPI status showed that in any nodal status, patients with 3.1–5cm/VPI tumors had significantly worse survival than patients with ≤3cm/VPI tumors (p =0.019) and patients with 3.1–5cm/non-VPI tumors (p =0.001). On the other hand, there was no significant difference in the OS between patients with 3.1–5cm/VPI tumors and patients with 5.1–7cm tumors regardless of lymph node metastasis (T2b tumors). Similar relationships were observed among these groups with N0 disease. Conclusion: We identified the presence of VPI as an independent poor prognostic factor in patients with NSCLC of ≤7cm. Tumors 3.1–5cm with VPI should be upstaged to T2b tumors in the future in the TNM classification of the Union of International Cancer Control staging system. In addition, the surgical strategy involving more extensive lymph node dissection for patients with ≤3cm/VPI tumors, especially ≤2cm/VPI, is warranted owing to more frequent lymph node metastasis. [Copyright &y& Elsevier]

OBJECTIVES Although an association between prognosis and lobar location of lung cancer, particularly the left lower lobe (LLL), has been suggested, the certainty of such association remains controversial. The purpose of this study was to evaluate the impact of tumour lobar location on surgical outcomes as an independent prognostic factor for survival in our non-small cell lung cancer (NSCLC) patient series. METHODS We retrospectively reviewed 978 NSCLC patients who underwent complete resection in our hospital between 2000 and 2007. We statistically analysed the association between clinicopathological factors and clinical outcomes. RESULTS Among the 978 patients reviewed, the NSCLC was located in the LLL in 143 (14.6%) patients, and lymph node involvement was identified in 210 patients (21.5%). The 5-year overall survival rates of patients whose NSCLC was located in the LLL and in other lobes (non-LLL) were 73.1 and 74.3%, respectively, and showed no significant association (P = 0.86). On the other hand, the 5-year survival rates of patients whose NSCLC occurred in the LLL (n = 33) and non-LLL (n = 177) and with lymph node metastasis were 32.7 and 57.7%, respectively, and showed a significant association (P = 0.01). Therefore, we performed a more detailed analysis on the 210 NSCLC patients with lymph node metastasis. On multivariate analysis, we found that LLL tumour (P = 0.02), tumour size >3 cm (P = 0.02) and N status (P < 0.001) were significant independent predictors for survival. CONCLUSIONS LLL tumours with lymph node metastasis are strongly associated with mortality in NSCLC patients. The location of the primary tumour may contribute in determining the optimal management strategy and accurate prediction of prognosis. [ABSTRACT FROM AUTHOR]

The optimal mode of surgery for ground-glass opacity dominant peripheral lung cancer defined with thoracic thin-section computed tomography remains unknown. We conducted a single-arm confirmatory trial to evaluate the efficacy and safety of sublobar resection for ground-glass opacity dominant peripheral lung cancer. Lung cancer with maximum tumor diameter 2.0 cm or less and with consolidation tumor ratio 0.25 or less based on thin-section computed tomography were registered. The primary end point was 5-year relapse-free survival. The planned sample size was 330 with the expected 5-year relapse-free survival of 98%, threshold of 95%, 1-sided α of 5%, and power of 90%. The trial is registered with University Hospital Medical Information Network Clinical Trials Registry, number University Hospital Medical Information Network 000002008. Between May 2009 and April 2011, 333 patients were enrolled from 51 institutions. Median age was 62 years (interquartile range, 56-68), and 109 were smokers. Median maximum tumor diameter was 1.20 cm (1.00-1.54). Median maximum tumor diameter of consolidation was 0 (0.00-0.20). The primary end point, 5-year relapse-free survival, was estimated on 314 patients who underwent sublobar resection. Operative modes were 258 wide wedge resections and 56 segmentectomies. Median pathological surgical margin was 15 mm (0-55). The 5-year relapse-free survival was 99.7% (90% confidence interval, 98.3-99.9), which met the primary end point. There was no local relapse. Grade 3 or higher postoperative complications based on Common Terminology Criteria for Adverse Effect v3.0 were observed in 17 patients (5.4%), without any grade 4 or 5. Sublobar resection with enough surgical margin offered sufficient local control and relapse-free survival for lung cancer clinically resectable N0 staged by computed tomography with 3 or fewer peripheral lesions 2.0 cm or less amenable to sublobar resection and with a consolidation tumor ratio of 0.25 or less. [Display omitted] [ABSTRACT FROM AUTHOR]

Minichromosome maintenance (MCM) protein deregulation is associated with tumor formation, progression and malignant transformation. MCM2 is frequently expressed during premalignant lung cell proliferation and is a sensitive marker for the early detection of pulmonary malignant lesions. The present study was undertaken to investigate whether MCM2 expression is of clinical and prognostic value in patients who have undergone lung adenocarcinoma resection. Between January 2009 and December 2010, 102 consecutive patients underwent complete pulmonary resection (involving lobectomy or more extensive resection) for lung adenocarcinoma at St. Marianna Medical University Hospital (Kanagawa, Japan). Among those, 73 patients, who had a final pathological diagnosis of lung adenocarcinoma measuring ≥10 mm, were enrolled in the present study. High MCM2 expression was found in 35 patients (48.0%). Univariate analysis of the overall survival (OS) revealed that pathological stage and MCM2 expression were significant prognostic factors in lung adenocarcinoma (P<0.001 and P<0.002, respectively). Univariate analysis of the recurrence-free survival (RFS), the significant prognostic factors included pathological stage, EGFR mutation status and MCM2 expression (P<0.001, P<0.034 and P<0.003, respectively). On multivariate survival analysis, high MCM2 expression and pathological stage II-III were identified as independent strong prognostic factors (OS: HR=5.084, 95% CI: 1.715-15.080, P=0.003; RFS: HR=2.761, 95% CI: 1.090-6.998, P=0.032). Therefore, the findings of the present study demonstrated that MCM2 may serve as a potential biomarker and therapeutic target for lung adenocarcinoma. [ABSTRACT FROM AUTHOR]

A few studies have reported on the variability of the variant allele frequency (VAF) of gene mutations and the relationship between VAF and the therapeutic effect of molecular-targeted drugs. This joint study was conducted from May 2020 to January 2022 between St. Marianna University School of Medicine and the DNA Chip Research Institute. Cytology samples were used to verify the usefulness of a lung cancer compact panel test, which is a high-sensitivity next-generation sequencing (NGS) gene panel test. We analyzed the distribution of VAF and the duration of the initial molecular-targeted drug administration in patients with advanced-stage epidermal growth factor receptor (EGFR) mutations. Of the 196 patients diagnosed with non-small cell carcinoma (NSCLC), gene mutations were detected in 114 (58.2%) cases and in 68.7% of patients with adenocarcinomas (an increased detection rate). A VAF of 30% or more for DNA mutations was confirmed in 35 patients (33.7%), 10% to <30% in 38 (36.5%), and <10% in 31 (29.8%), including 18 patients (17.3%) with <6%, which is considered the lower limit of the LOD for other companion diagnostic kits. EGFR mutations were detected in 59 patients (30%), of whom 35 were in an advanced stage and received molecular-targeted drugs as their initial treatment. Groups A and B comprised patients with a VAF of ≥10% and <10%, respectively, with 27 patients (median VAF 30.6%, range 11.4–77%) in group A and 8 (median VAF 5.4%, range 0.1–8.5%) in group B. The duration of the administration of molecular-targeted drugs was 17 months (range 3–42 months) in group A and 14 months (range 1–45 months) in group B, with no statistically significant difference between the two groups (p-value = 0.7). Twenty-seven percent of patients had a VAF < 10%. Even in patients with a low VAF for gene mutations, sufficient therapeutic effects were observed with molecular-targeted drugs, suggesting the importance of detecting mutations using a highly sensitive method at initial diagnosis. Further prospective validation studies of a larger number of cases are warranted. [ABSTRACT FROM AUTHOR]

Open in new tab Download slide OBJECTIVES This study aimed to identify the risk factors for pulmonary functional deterioration after wedge resection for early-stage lung cancer with ground-glass opacity, which remain unclear, particularly in low-risk patients. METHODS We analysed 237 patients who underwent wedge resection for peripheral early-stage lung cancer in JCOG0804/WJOG4507L, a phase III, single-arm confirmatory trial. The changes in forced expiratory volume in 1 s were calculated pre- and postoperatively, and a cutoff value of −10%, the previously reported reduction rate after lobectomy, was used to divide the patients into 2 groups: the severely reduced group (≤−10%) and normal group (>−10%). These groups were compared to identify predictors for severe reduction. RESULTS Thirty-seven (16%) patients experienced severe reduction. Lesions with a total tumour size ≥1 cm were significantly more frequent in the severely reduced group than in the normal group (89.2% vs 71.5%; P  =   0.024). A total tumour size of ≥1 cm [odds ratio (OR), 3.287; 95% confidence interval (CI), 1.114–9.699: P  =   0.031] and pleural indentation (OR, 2.474; 95% CI, 1.039–5.890: P  =   0.041) were significant predictive factors in the univariable analysis. In the multivariable analysis, pleural indentation (OR, 2.667; 95% CI, 1.082–6.574; P  =   0.033) was an independent predictive factor, whereas smoking status and total tumour size were marginally significant. CONCLUSIONS Of the low-risk patients who underwent pulmonary wedge resection for early-stage lung cancer, 16% experienced severe reduction in pulmonary function. Pleural indentation may be a risk factor for severely reduced pulmonary function in pulmonary wedge resection. [ABSTRACT FROM AUTHOR]

Immunoglobulin G4‐related disease (IgG4‐RD) is a newly recognized disease, and therefore its clinical features are not yet fully understood. Here, we describe a surgical case of metachronous bilateral IgG4‐related pleuritis and postoperative chylothorax. This case could provide key insights into the pathology of IgG4‐RD from a surgical perspective. We present a 70‐year‐old woman who had a right pleural mass. Video‐assisted thoracoscopic pleural mass resection was performed, and the patient was diagnosed with right‐sided IgG4‐related pleuritis. Two years later, she was also diagnosed with left‐sided IgG4‐related pleuritis. We suspected the presence of IgG4‐positive plasma cell infiltration. Additionally, she experienced a complicated postoperative chylothorax on the left side. It is important to consider the altered course of lymphatic vessels when extensively removing the pleura near the right thoracic duct. The occurrence of metachronous bilateral IgG4‐associated pleuritis has not been previously reported, making this case particularly significant for understanding the pathology of IgG4‐RD from a surgical standpoint. [ABSTRACT FROM AUTHOR]

There are few prospective reports of transbronchial lung cryobiopsy (TBLC) for malignant tumors in combination with forceps biopsy. We investigated the clinical parameters in which TBLC is superior to forceps biopsy. This is a prospective cohort study to analyse the efficacy of TBLC for suspected malignancy. TBLC was performed after brushing cytology and forceps biopsy, and the diagnostic yield for TBLC, brushing cytology, and forceps biopsy were examined. Adverse events were defined as those requiring additional procedures. Next-generation sequencing (NGS) analysis was performed in each case of non-small cell lung cancer. Of the 100 patients, malignancy was confirmed in 94 cases. The diagnostic yield for TBLC/forceps biopsy/brushing cytology was 86/81/82% respectively, while the diagnostic yield for all procedures combined was 94%. There was no significant difference in the diagnostic yield between TBLC and forceps biopsy. When comparing the biopsy site, the diagnostic yield for TBLC at the lower lobe was significantly higher than forceps biopsy (P < 0.01). Endobronchial ultrasonography imaging using a guide-sheath did not significantly differ in the diagnostic yield of TBLC. The success rate of NGS for TBLC specimens was 100% (26 cases). Adverse events included two cases of severe bleeding. TBLC of peripheral lesions may improve the diagnostic yield when combined with forceps biopsy and brushing cytology. The diagnostic yield of TBLC was higher at the lower lobes. Furthermore, TBLC provided sufficient specimen quality for NGS. [ABSTRACT FROM AUTHOR]

Objectives The detection rate of small pulmonary nodules has recently increased and new techniques have been developed to improve diagnostic yield. The IASLC/ATS/ERS classification demonstrated a difference in prognosis depending on the histological subtypes of lung adenocarcinoma. We evaluated the association between high-resolution computed tomography (HRCT) findings and the classification of these tumors. Methods We reviewed the data of 220 lung adenocarcinoma (≤3 cm) patients who received complete resection with lymph node dissection in our hospital. From the HRCT findings, the tumors were classified into the following 3 categories: pure-solid nodules, part-solid nodules, or pure ground-glass opacity (GGO) nodules. Pathological invasion factor (PIF) was evaluated by the degree of blood vessel invasion, lymphatic permeation, and visceral pleural invasion. Results The tumors were classified as pure GGO nodules in 16 patients, part-solid nodules in 91, and pure-solid nodules in 113 from the HRCT findings. Tumors were diagnosed as noninvasive or minimally invasive adenocarcinomas (NMIADs) in 44 patients, and invasive adenocarcinomas (IADs) in 176. Lymph node metastasis was present in 31 patients (14.1%) and PIF in 101 (45.9%). All pure-solid nodules were IADs with a high PIF frequency (75.2%) or with lymph node metastasis (26.5%). All pure GGO nodules were NMIADs or lepidic-predominant adenocarcinomas. Among the part-solid nodules, IAD was detected in 67.0% of the patients and PIF in 16.5%. The consolidation/tumor (C/T) ratio and consolidation size were associated with IAD (optimal cut-off values: 0.4 and 8 mm, respectively) and PIF (0.8 and 15 mm, respectively). Conclusions The HRCT findings correlated with the IASLC/ATS/ERS classification and were useful for evaluating the histological nature of the tumors. Most pure-solid tumors had the potential for high-grade malignancy, including PIF and lymph node metastasis. For part-solid tumors, the C/T ratio and consolidation size were important for predicting PIF and for diagnosing IAD according to this classification. [ABSTRACT FROM AUTHOR]

Simple Summary: The gold standard for genetic panel test samples is considered to be tissue specimens. However, in clinical practice, tissue specimens are often unavailable. Therefore, using an amplicon-based high-sensitivity next-generation sequencing panel test capable of measuring eight druggable genes, we enrolled patients who underwent diagnostic procedures to evaluate analysis accuracy, nucleic acid yield, and quality using cytological specimens. Cytological specimens were suitable for both nucleic acid yield and specimen quality due to the ease of collection and processing. Cytological sample analysis detected gene mutations in 68.7% of lung adenocarcinomas, and these samples were consistent with companion diagnostic tests 99.5% of the time. Moreover, the allele frequency of gene mutations in cytological specimens showed a high correlation with tissue specimens. This is the first study to prospectively evaluate the feasibility of a lung cancer gene panel test using cytological specimens. Background: Genetic panel tests require sufficient tissue samples, and therefore, cannot always be performed. Although collecting cytological specimens is easier than tissue collection, there are no validation studies on the diagnostic accuracy of lung cancer gene panel tests using cytology samples. Methods: Using an amplicon-based high-sensitivity next-generation sequencing panel test capable of measuring eight druggable genes, we prospectively enrolled consecutive patients who underwent diagnostic procedures. We evaluated the analysis accuracy rate, nucleic acid yield, and the quality of cytological specimens under brushing, needle aspiration, and pleural effusion. We then compared these specimens with collected tissue samples. Results: In 163 prospectively enrolled cases, nucleic acid extraction and analysis accuracy was 100% in cases diagnosed with adenocarcinoma. Gene mutations were found in 68.7% of cases with 99.5% (95% CI: 98.2–99.9) concordance to companion diagnostics. The median DNA/RNA yield and DNA/RNA integrity number were 475/321 ng and 7.9/5.7, respectively. The correlation coefficient of the gene allele ratio in 64 cases compared with tissue samples was 0.711. Conclusion: The success of gene analysis using cytological specimens was high, and the yield and quality of the extracted nucleic acid were sufficient for panel analysis. Moreover, the allele frequency of gene mutations in cytological specimens showed high correlations with tissue specimens. [ABSTRACT FROM AUTHOR]