Improved platelet separation performance from whole blood using an acoustic fluidics system.

This study investigated the effectiveness of acoustic separation for platelet analysis in patients with non-small-cell lung cancer (NSCLC), comparing it with traditional centrifugation methods. In total, 10 patients with NSCLC and 10 healthy volunteers provided peripheral blood samples, which were processed using either acoustic separation or centrifugation to isolate platelets. The study included whole transcriptome analysis of platelets, peripheral blood mononuclear cells, and tumor tissue samples, employing hierarchical clustering and Gene Ontology analysis to explore gene expression differences. Acoustic separation proved more efficient than centrifugation in terms of platelet yield, recovery rate, and RNA yield. Gene expression profiles of platelets from patients with NSCLC showed distinct patterns compared with healthy volunteers, indicating tumor-influenced alterations. Gene Ontology analysis revealed enrichment in pathways associated with platelet activation and the tumor microenvironment. This finding indicates the potential of acoustic isolation in platelet separation and its relevance in understanding the unique gene expression profile of platelets in patients with NSCLC. The findings of this study suggested that platelets from cancer patients separated by acoustic techniques exhibited tumor-specific alterations and provided new insights into the diagnosis of cancer in platelet analysis systems in clinical practice.

Differences in postoperative prognosis between early-stage lung adenocarcinoma and squamous cell carcinoma.

BACKGROUND: Although prognosis and treatments differ between small-cell- and nonsmall-cell carcinoma, comparisons of the histological types of NSCLC are uncommon. Thus, we investigated the oncological factors associated with the prognosis of early-stage adenocarcinoma and squamous cell carcinoma. METHODS: We retrospectively compared the clinicopathological backgrounds and postoperative outcomes of patients diagnosed with pathological stage I-IIA adenocarcinoma and squamous cell carcinoma primary lung cancer completely resected at our department from January 2007 to December 2017. Multivariable Cox regression analysis for overall survival and recurrence-free survival was performed. RESULTS: The median follow-up duration was 55.2 months. The cohort consisted of 532 adenocarcinoma and 96 squamous cell carcinoma patients. A significant difference in survival was observed between the two groups, with a 5-year overall survival rate of 90% (95% confidence interval 86-92%) for adenocarcinoma and 77% (95% CI 66-85%) for squamous cell carcinoma (P < 0.01) patients. Squamous cell carcinoma patients had worse outcomes compared to adenocarcinoma patients in stage IA disease, but there were no significant differences between the two groups in stage IB or IIA disease. In multivariate analysis, invasion diameter was associated with overall survival in adenocarcinoma (hazard ratio 1.76, 95% confidence interval 1.36-2.28), but there was no such association in squamous cell carcinoma (hazard ratio 0.73, 95% confidence interval 0.45-1.14). CONCLUSIONS: The importance of tumor invasion diameter in postoperative outcomes was different between adenocarcinoma and squamous cell carcinoma. Thus, it is important to consider that nonsmall-cell carcinoma may have different prognoses depending on the histological type, even for the same stage.

The Lung Cancer Surgical Study Group of the Japan Clinical Oncology Group: outstanding contribution and entering a new phase.

The Lung Cancer Surgical Study Group (LCSSG) of the Japan Clinical Oncology Group (JCOG) was organized in 1986 and initially included 26 collaborative institutions, which has increased to 52 institutions currently. JCOG-LCSSG includes thoracic surgeons, medical oncologists, pathologists, and radiotherapists. In the early period, the JCOG-LCSSG mainly focused on combined modality therapies for lung cancer. Since the 2000s, the JCOG-LCSSG has investigated adequate modes of surgical resection for small-sized and peripheral non-small cell lung cancer and based on the radiological findings of whole tumor size and ground-glass opacity. Trials, such as JCOG0802, JCOG0804, and JCOG1211, have shown the appropriateness of sublobar resection, which has significantly influenced routine clinical practice. With the introduction of targeted therapy and immunotherapy, treatment strategies for lung cancer have changed significantly. Additionally, with the increasing aging population and medical costs, tailored medicine is strongly recommended to address medical issues. To ensure comprehensive treatment, strategies, including surgical and nonsurgical approaches, should be developed. Currently, the JCOG-LCSSG has conducted numerous clinical trials to adjust the diversity of lung cancer treatment strategies. This review highlights recent advancements in the surgical field, current status, and future direction of the JCOG-LCSSG.

Updated review of perioperative treatment for non-small-cell lung cancer in the new era of immune checkpoint inhibitors: past, present, and future.

The perioperative treatments for non-small cell lung cancer (NSCLC) should control both local and microscopic systemic disease, because the survival of patients with NSCLC who underwent surgical resection alone has been dismal except in stage IA patients. One way to improve surgical outcome is the administration of chemotherapy before or after the surgical procedure. During the last two decades, many clinical studies have focused on developing optimal adjuvant or neoadjuvant cisplatin-based chemotherapy regimens that can be combined with surgical treatment and/or radiotherapy. Based on the results of those clinical studies, multimodality therapy has been considered to be an appropriate treatment approach for locally advanced NSCLC patients. When nodal involvement is discovered postoperatively, adjuvant cisplatin-based chemotherapy has conferred an overall survival benefit. More recently, neoadjuvant and/or adjuvant use of immunotherapy adding to the cisplatin-based chemotherapy has been revealed to improve survival of the patients with locally advanced NSCLC in many large-scale clinical trials; although, optimal treatment strategies are still evolving.

A multicenter propensity score-matched analysis of lymphadenectomy in N1-positve lung cancer.

OBJECTIVES: Selective mediastinal lymph node dissection based on lobe-specific metastases is widely recognized in daily practice. However, the significance of mediastinal lymph node dissection for N1-positive tumors has not been elucidated. METHODS: We retrospectively reviewed 359 patients with N1-positive lung cancer who underwent lobectomy with systematic mediastinal lymph node dissection (systematic lymph node dissection) (n = 150) and lobe-specific mediastinal lymph node dissection (lobe-specific lymph node dissection) (n = 209). The operative and postoperative results and their propensity score-matched pairs were compared. The factors affecting survival were assessed using competing risk and multivariable analyses. RESULTS: The cumulative incidence of recurrence and the cumulative incidence of cancer-specific death were not significantly different between systematic and lobe-specific lymph node dissection in entire cohort. In the propensity score-matched cohort (83 pairs), systematic lymph node dissection tended to detect N2 lymph node metastasis more frequently (55.4 vs. 41%, P = 0.087). Eleven patients (13.2%) in the systematic lymph node dissection group had a metastatic N2 lymph node 'in the systematic lymph node dissection field' that lobe-specific lymph node dissection did not dissect. The oncological outcomes between patients undergoing systematic lymph node dissection (5-year cumulative incidence of recurrence, 62.1%; 5-year cumulative incidence of cancer-specific death, 27.9%) and lobe-specific lymph node dissection (5-year cumulative incidence of recurrence, 60.1%; 5-year cumulative incidence of cancer-specific death, 23.3%) were similar. The propensity score-adjusted multivariable analysis for cumulative incidence of recurrence revealed that the prognosis associated with systematic lymph node dissection was comparable with the prognosis with lobe-specific lymph node dissection (hazard ratio, 1.17; 95% confidence interval, 0.82-1.67; P = 0.37). CONCLUSIONS: The extent of lymph node dissection can affect accurate pathological staging; however, it was not associated with survival outcome in the treatment of N1-positive lung cancer.

Feasibility of repeated ipsilateral anatomical pulmonary resection.

PURPOSE: This study aimed to elucidate the feasibility of repeated ipsilateral anatomical pulmonary resection. METHODS: The subjects of this retrospective analysis were 50 patients who underwent ipsilateral anatomical pulmonary resection after major lung surgery. The patients were divided into two groups according to the type of primary operation performed: a repeated anatomical pulmonary resection group (RA group; n = 24) and an anatomical pulmonary resection after wedge resection group (AW group; n = 26). We compared the perioperative outcomes of the two groups. RESULTS: Completion lobectomy was performed in 9 of the 24 patients (38%) from the RA group and adhesion of the pulmonary hilum was more severe in this group (P = 0.004). Although the operative time was significantly longer in the RA group (P = 0.030), there was no significant difference in the amount of blood loss (P = 0.217) between the groups. A significantly higher rate of severe postoperative complications was observed in the RA group (42%) than in the AW group (12%) (P = 0.024). None of the patients who underwent repeated surgery died within 90 days postoperatively. CONCLUSION: Although repeated anatomical pulmonary resection is a more challenging procedure than anatomical resection after wedge resection, it does not increase short-term mortality; therefore, it is a feasible treatment option.

Phase II study of carboplatin-paclitaxel alone or with bevacizumab in advanced sarcomatoid carcinoma of the lung: HOT1201/NEJ024.

OBJECTIVES: Only a few prospective studies have been conducted to examine the efficacy and safety of systemic chemotherapy for patients with pulmonary sarcomatoid carcinomas (PSCs). There is, thus, a crucial need to develop novel treatment strategies for this rare tumor. PATIENTS AND METHODS: Chemotherapy-naïve patients with histologically confirmed PSCs were assigned to receive either carboplatin/paclitaxel alone (CP) or with bevacizumab (CPB) followed by bevacizumab maintenance. The primary endpoint was overall response rate (ORR). Secondary endpoints included overall survival (OS), progression-free survival (PFS), and safety. RESULTS: This study was closed before accumulating the expected number of cases due to slow patient accrual. Eventually, 16 patients were enrolled. The ORR was 25.0% and disease control rate was 56.3%. CPB was administered in all four patients with an objective response [partial response (PR)]; among the four PR cases, two patients had pleomorphic carcinoma, and two had carcinosarcoma. Median PFS and median survival time (MST) in all the enrolled patients were 2.6 months and 8.8 months, respectively. Median PFS was 1.2 months in the CP group and 4.2 months in the CPB group. In addition, MST was 7.9 months in the CP group and 11.2 months in the CPB group. Hematological and non-hematological adverse events were common and reversible, although ileus (grade 4) and nasal bleeding (grade 3) occurred in one case each in the CPB group. CONCLUSIONS: CPB might be effective as first-line treatment for PSCs. Further study is warranted to clarify the role of cytotoxic chemotherapy for this rare and aggressive tumor. CLINICAL TRIALS REGISTRATION: University Hospital Medical Information Network (UMIN) Clinical Trial Registry (UMIN000008707).

Postoperative Pulmonary Function After Complex Segmentectomy.

BACKGROUND: Segmentectomy has been increasingly used for lung cancer treatment, however there are very limited data evaluating the postoperative pulmonary function of patients treated with complex segmentectomy. We evaluated the postoperative pulmonary function of patients who underwent complex segmentectomy compared with simple segmentectomy, wedge resection, and lobectomy. METHODS: We retrospectively analyzed data from 580 patients who underwent surgical resection. The patients were divided into four groups: complex segmentectomy (n = 135), simple segmentectomy (n = 83), wedge resection (n = 89), and lobectomy (n = 273). Functional testing included forced vital capacity (FVC), forced expiratory volume in 1 s (FEV1), and predicted diffusing capacity of the lung for carbon monoxide (%DLCO) measured preoperatively and at 12 months after surgery. RESULTS: During the postoperative course, the complex segmentectomy and simple segmentectomy groups showed a comparable course of pulmonary function. The complex segmentectomy group significantly preserved pulmonary function compared with the lobectomy group (FVC, p = 0.017; FEV1, p = 0.010; %DLCO, p = 0.0043). A similar trend was observed even when restricted to lung diseases in the right upper lobe. On the other hand, when comparing complex segmentectomy with wedge resection, complex segmentectomy showed a trend that was more disadvantageous than wedge resection, but this difference was not significant (FVC, p = 0.19; FEV1, p = 0.40; %DLCO, p = 0.96). CONCLUSIONS: Complex segmentectomy showed comparable postoperative pulmonary functions as simple segmentectomy. Complex segmentectomy could preserve pulmonary function significantly compared with lobectomy and did not result in significant loss compared with wedge resection.

Patient Selection of Sublobar Resection Using Visual Evaluation of Positron-Emission Tomography (PET) for Early-Stage Lung Adenocarcinoma.

BACKGROUND: This study aimed to investigate the efficacy of the Deauville criteria (a 5-point visual scale criteria) in assessing the accumulation of [18F]-fluoro-2-deoxy-D-glucose (FDG) on positron-emission tomography (PET)/computed tomography (CT) for predicting prognosis of early-stage lung adenocarcinoma and selecting candidates for sublobar resection. METHODS: This retrospective study included 648 patients undergoing curative resection for clinical N0 lung adenocarcinoma with a whole tumor size of 3 cm or smaller between April 2007 and March 2019. Accumulations of the FDG on PET/CT scans were scored using the Deauville criteria (Deauville score), and correlations between the Deauville score and prognosis were analyzed. RESULTS: The recurrence-free survival (RFS) was significantly better for the patients with a Deauville score of 1 or 2 (n = 415, 5-year RFS, 92.6%) than for those with a score of 3 (n = 82, 5-year RFS, 72.7%; P < 0.001) or a score of 4 or 5 (n = 151, RFS, 70.8%; P < 0.001). The RFS did not differ significantly among the patients with Deauville scores of 1 and 2 who underwent wedge resection (n = 102, 5-year RFS, 90.5%), segmentectomy (n = 188, RFS, 95.1%; P = 0.355), and lobectomy (n = 125, RFS, 91.1%; P = 0.462). CONCLUSION: The 5-point-scale evaluation of FDG accumulation on PET/CT was useful in predicting the prognosis for patients with early-stage lung adenocarcinoma. Lung adenocarcinoma patients with a whole tumor size of 3 cm or smaller and a Deauville score of 1 or 2 can be candidates for sublobar resection.

Systematic Versus Lobe-Specific Mediastinal Lymphadenectomy for Hypermetabolic Lung Cancer.

BACKGROUND: The optimal extent of lymph node dissection (LND) for hypermetabolic tumors that are associated with high rates of nodal disease, recurrence, or mortality has not been elucidated. METHODS: We reviewed 375 patients who underwent lobectomy with lymphadenectomy for clinical T2-3 N0-1 M0 hypermetabolic non-small cell lung cancer (NSCLC) [maximum standard uptake value (SUVmax) ≥ 6.60] via a multicenter database. Extent of LND was classified into systematic mediastinal LND (systematic LND) and lobe-specific mediastinal LND (lobe-specific LND). Postoperative outcomes after lobectomy with systematic LND (n = 128) and lobe-specific LND (n = 247) were analyzed for all patients and their propensity-score-matched pairs. RESULTS: Cancer-specific survival (CSS) and recurrence-free interval (RFI) of the systematic LND group were not significantly different from those of the lobe-specific LND group in the nonadjusted whole cohort. In the propensity-score-matched cohort (101 pairs), systematic LND dissected significantly more lymph nodes (20.0 versus 16.0 nodes, P = 0.0057) and detected lymph node metastasis more frequently (53.5% vs. 33.7%, P = 0.0069). Six (5.9%) patients in the systematic LND group had a metastatic N2 lymph node "in the systematic LND field" that lobe-specific LND could not dissect. The systematic LND group tended to have better prognosis than the lobe-specific LND group (5-year CSS rates, 82.6% versus 69.6%; 5-year RFI rates, 56.6% vs. 47.3%). CONCLUSIONS: Systematic LND was found to harvest more metastatic lymph nodes and provide better oncological outcome than lobe-specific LND in a cohort of hypermetabolic NSCLC patients.

Prognostic role of interstitial pneumonia with or without emphysema in patients with clinical stage I lung cancer.

OBJECTIVES: The prognostic role of interstitial pneumonia with emphysema in lung cancer is not fully understood. This study aimed to examine the prognostic role of the presence of emphysema in patients with clinical stage I lung cancer and interstitial pneumonia. METHODS: The presence of interstitial pneumonia and emphysema was evaluated on preoperative high-resolution computed tomography. In total, 836 consecutive patients with clinical stage I lung cancer who underwent complete resection between April 2007 and March 2016 were retrospectively analyzed using the log-rank test and Cox proportional hazard model to examine survival differences. RESULTS: There was a significant difference in 5-year overall survival between patients with interstitial pneumonia and emphysema (n = 65) and those without (n = 771) (62.6% vs. 86.5%; P < 0.001). However, in patients with interstitial pneumonia on high-resolution computed tomography, there was no significant difference in 5-year overall survival between patients with emphysema (n = 65) and those without emphysema (n = 50) (62.6% vs. 59.4%, P = 0.84). Multivariable backward stepwise Cox proportional hazard analysis in patients with interstitial pneumonia showed that histology, %diffusing capacity of the lungs for carbon monoxide, radiologic interstitial pneumonia pattern and surgical procedure were independent prognostic factors for overall survival, but the presence of emphysema was not. CONCLUSIONS: The presence of emphysema was not an independent prognostic factor for overall survival in patients with clinical stage I lung cancer with interstitial pneumonia. Poor survival of patients with IP and emphysema may be due to the presence of interstitial pneumonia.

Appropriate Extent of Lymphadenectomy in Segmentectomy: A Multicenter Study.

BACKGROUND: The significance of lymphadenectomy is yet to be fully examined in segmentectomy. We compared the oncological outcomes of mediastinal lymph node dissection (LND) and hilar LND for lung cancer treated with segmentectomy via a multicenter database using propensity score-matched analysis. METHODS: We reviewed 357 clinical stage IA radiologically solid-dominant lung cancer patients who underwent segmentectomy with lymphadenectomy. The extent of LND was classified into systematic/lobe-specific mediastinal LND and hilar LND only groups. Postoperative results after segmentectomy with mediastinal LND (n = 179) and hilar LND (n = 178) were analyzed for all patients and their propensity score-matched pairs. RESULTS: Cancer-specific survival (CSS) and recurrence-free interval (RFI) rates for the mediastinal LND group were determined to be not significantly different compared with the hilar LND group in all non-adjusted cohorts. In the propensity score-matched cohort (129 pairs), mediastinal LND harvested more lymph nodes compared with hilar LND, and both groups had significantly different pathological stages (P = 0.015). Adjuvant chemotherapy was performed in 10 (7.8%) patients in the mediastinal LND group and 4 (3.1%) in the hilar LND group. The mediastinal LND group tended to have better prognosis than the hilar LND group (5-year CSS rates, 97.4% vs 93.2%; 5-year RFI rates, 93.5% vs 88.5%). CONCLUSIONS: Mediastinal LND was found to provide more appropriate pathological staging compared with hilar LND in patients with segmentectomy by harvesting more lymph nodes. In addition, mediastinal LND might lead to better oncological outcome than hilar LND in segmentectomy.

Risk of death due to other causes is lower among octogenarians with non-small cell lung cancer after wedge resection than lobectomy/segmentectomy.

OBJECTIVE: We aimed to determine the influences of surgical procedures on the postoperative death of octogenarians with clinical Stage IA non-small cell lung cancer excluding cT1mi. METHODS: We compared overall survival and the cumulative incidence of death due to all and other causes among 1 130 279, and 191 consecutive patients aged ≤79 and ≥80 years after lobectomy, segmentectomy and wedge resection at three institutions. Death due to other causes was defined as death due to any cause except non-small cell lung cancer. RESULTS: The median followup was 53 months. The 5-year overall survival rates for patients aged ≥ 80 and ≤ 79 years after lobectomy, segmentectomy and wedge resection were respectively, 78.0% (95% confidence interval, 63.8%-87.2%) versus 91.2% (95% confidence interval, 89.0%-92.9%), 68.1% (95% confidence interval, 45.2%-83.1%) versus 90.0% (95% confidence interval, 84.6%-93.5%), and 62.7% (95% confidence interval, 44.0-76.7%) versus 84.4% (95% confidence interval, 76.3%-89.9%) (P < 0.01 for all). The cumulative incidence of death due to other causes after wedge resection was similar between patients aged ≥ 80 and ≤ 79 years (P = 0.45), but significantly higher in those aged ≥ 80, than ≤ 79 years after lobectomy or segmentectomy (P = 0.00015 and 0.00091, respectively). CONCLUSIONS: The influence of wedge resection on death due to other causes was lower than that of lobectomy or segmentectomy in patients with non-small cell lung cancer aged ≥ 80 years. Wedge resection might be a useful option for octogenarians even if they can tolerate lobectomy/segmentectomy to avoid postoperative death due to causes other than non-small cell lung cancer.

Surgical challenges in multimodal treatment of N2-stage IIIA non-small cell lung cancer.

Locally advanced non-small cell lung cancer, especially mediastinal lymph node metastasis-positive stage IIIA-N2 cancer, is a heterogeneous disease state characterized by anatomically locally advanced disease with latent micrometastases. Thus, surgical resection or radiotherapy alone has historically failed to cure this disease. During the last three decades, persistent efforts have been made to develop a suitable treatment modality to overcome these problems using chemotherapy and/or radiotherapy with surgical resection. However, the role of surgical resection remains unclear, and the standard treatment for stage IIIA-N2 disease is concurrent chemoradiotherapy. In general, adjuvant chemotherapy is indicated for completely resected pathological stage IB disease or lymph node metastasis-positive pathological stage II or IIIA disease. Platinum-based doublet cytotoxic chemotherapy is currently the standard regimen. Additionally, post-operative radiotherapy might be indicated for post-operatively proven mediastinal lymph node metastasis; i.e. clinical N0-1 and pathological N2 disease. With the remarkable progression that has recently been made in the field of chemotherapy, such as advances in molecular targeting agents and immune checkpoint inhibitors, the basic policy of chemotherapy has been shifting to personalized treatment based on the individual patient's oncogene driver mutation status, immune status and other parameters. The same trend is being seen in the treatment of stage IIIA-N2 disease. We should consider the past and upcoming results of several clinical trials to optimize the coming era of personalized treatment.

Recent advances and future perspectives in adjuvant and neoadjuvant immunotherapies for lung cancer.

The superior efficacy of immune checkpoint inhibitors for the treatment of advanced non-small cell lung cancer has inspired many clinical trials to use immune checkpoint inhibitors in earlier stages of lung cancer worldwide. Based on the theoretical feasibility that neoantigens derived from a tumor tissue are present in vivo, some clinical trials have recently evaluated the neoadjuvant, rather than the adjuvant, use of immune checkpoint inhibitors. Some of these trials have already produced evidence on the safety and efficacy of immune checkpoint inhibitors in a neoadjuvant setting, with a favorable major pathologic response and few adverse events. In the most impactful report from Johns Hopkins University and the Memorial Sloan Kettering Cancer Center, the programed death-1 inhibitor nivolumab was administered to 21 patients in a neoadjuvant setting. The authors reported a major pathologic response rate of 45%, with no unexpected delay of surgery related to the adverse effects of nivolumab. The adjuvant as well as the neoadjuvant administration of immune checkpoint inhibitors has also been considered in various clinical trials, with or without the combined use of chemotherapy or radiotherapy. The development of appropriate biomarkers to predict the efficacy of immune checkpoint inhibitors is also underway. The expression of programed death ligand-1 and the tumor mutation burden are promising biomarkers that have been evaluated in many settings. To establish an appropriate method for using immune checkpoint inhibitors in combination with surgery, the Lung Cancer Surgical Study Group of the Japan Clinical Oncology Group will manage clinical trials using a multimodality treatment, including immune checkpoint inhibitors and surgery.

Serum S100 calcium-binding protein A4 as a novel predictive marker of acute exacerbation of interstitial pneumonia after surgery for lung cancer.

BACKGROUND: Acute exacerbation (AE) of interstitial pneumonia (IP) is the most fatal complication after lung resection for lung cancer. To improve the prognosis of lung cancer with IP, the risk factors of AE of IP after lung resection should be assessed. S100 calcium-binding protein A4 (S100A4) is a member of the S100 family of proteins and is a known marker of tissue fibrosis. We examined the usefulness of S100A4 in predicting AE of IP after lung resection for lung cancer. METHODS: This study included 162 patients with IP findings on preoperative high-resolution computed tomography scan who underwent curative-intent lung resection for primary lung cancer between April 2007 and March 2019. Serum samples were collected preoperatively. Resected lung tissue from 76 patients exhibited usual IP (UIP) pattern in resected lung were performed immunohistochemistry (IHC). Relationship between S100A4 and the incidence of AE of IP and short-term mortality was analyzed. RESULTS: The receiver operating characteristic area under the curve for serum S100A4 to predict postoperative AE of IP was 0.871 (95% confidence interval [CI], 0.799-0.943; P < 0.001), with a sensitivity of 93.8% and a specificity of 75.3% at the cutoff value of 17.13 ng/mL. Multivariable analysis revealed that a high serum S100A4 level (> 17.13 ng/mL) was a significant risk factor for AE of IP (odds ratio, 42.28; 95% CI, 3.98-449.29; P = 0.002). A 1-year overall survival (OS) was significantly shorter in patients with high serum levels of S100A4 (75.3%) than in those with low serum levels (92.3%; P = 0.003). IHC staining revealed that fibroblasts, lymphocytes, and macrophages expressed S100A4 in the UIP area, and the stroma and fibrosis in the primary tumor expressed S100A4, whereas tumor cells did not. CONCLUSIONS: Serum S100A4 had a high predictive value for postoperative AE of IP and short-term mortality after lung resection.

Diagnostic performance of peripheral leukocyte telomere G-tail length for detecting breast cancer.

The telomere G-tail (G-tail) plays an essential role in maintaining chromosome stability. In this study, we assessed the leukocyte G-tail length of breast cancer (BC) patients and cancer-free individuals and evaluated the association between the G-tail length and the presence of BC. A significant shortening of the median G-tail length was observed in BC patients compared with cancer-free individuals and was found in the early phase of BC. Our study indicated that the leukocyte G-tail length might be a potential biomarker for BC detection.

Predicting the presence of breast cancer using circulating small RNAs, including those in the extracellular vesicles.

Emerging evidence indicates that small RNAs, including microRNAs (miRNAs) and their isoforms (isomiRs), and transfer RNA fragments (tRFs), are differently expressed in breast cancer (BC) and can be detected in blood circulation. Circulating small RNAs and small RNAs in extracellular vesicles (EVs) have emerged as ideal markers in small RNA-based applications for cancer detection. In this study, we first undertook small RNA sequencing to assess the expression of circulating small RNAs in the serum of BC patients and cancer-free individuals (controls). Expression of 3 small RNAs, namely isomiR of miR-21-5p (3' addition C), miR-23a-3p and tRF-Lys (TTT), was significantly higher in BC samples and was validated by small RNA sequencing in an independent cohort. Our constructed model using 3 small RNAs showed high diagnostic accuracy with an area under the receiver operating characteristic curve of 0.92 and discriminated early-stage BCs at stage 0 from control. To test the possibility that these small RNAs are released from cancer cells, we next examined EVs from the serum of BC patients and controls. Two of the 3 candidate small RNAs were identified, and shown to be abundant in EVs of BC patients. Interestingly, these 2 small RNAs are also more abundantly detected in culture media of breast cancer cell lines (MCF-7 and MDA-MB-231). The same tendency in selective elevation seen in total serum, serum EV, and EV derived from cell culture media could indicate the efficiency of this model using total serum of patients. These findings indicate that small RNAs serve as significant biomarkers for BC detection.

Intense Expression of EGFR L858R Characterizes the Micropapillary Component and L858R Is Associated with the Risk of Recurrence in pN0M0 Lung Adenocarcinoma with the Micropapillary Component.

BACKGROUND: Lung adenocarcinoma with the micropapillary (MP) component poses a higher risk of recurrence even when the MP component is not predominant. This study explored genetic features associated with highly malignant behavior of lung adenocarcinoma with the MP component. METHODS: The MP and papillary (PaP) components were captured separately in three patients. Comprehensive mRNA expressions of somatic variants were compared between the MP and PaP components of each patient using next-generation sequencing (NGS). The protein expression of the NGS-detected variant was validated by immunohistochemistry. The prognostic impact of the detected variant was evaluated in 288 adenocarcinoma patients with resection of pN0M0. RESULTS: In two cases, NGS suggested higher RNA expression of EGFR L858R in the MP component than in the PaP component (allele frequency, 0.485 vs. 0.155 and 1.000 vs. 0.526, respectively; P < 0.001 for both). Immunohistochemistry validated intense expression of L858R in the MP component of 27 MP-positive (MP+) patients. Among 288 pN0M0 patients, L858R was more frequently harbored in the MP+ patients than in the MP-negative (MP-) patients. The MP+ patients harboring L858R showed significantly worse recurrence-free survival (RFS) than the MP+ patients without L858R (median RFS 38.7 and 55.0 months, respectively; hazard ratio [HR] 3.004; 95% confidence interval [CI] 1.306-9.132; P = 0.012). Multivariate analysis of the MP+ patients showed that positive L858R status was associated with poorer RFS (HR 2.976; 95% CI 1.190-7.442; P = 0.020). CONCLUSIONS: EGFR L858R was more frequently harbored in the MP+ adenocarcinoma patients than in the MP- adenocarcinoma patients. Intense expression of L858R in the MP component was suggested, and the MP+ patients harboring L858R were at comparatively higher risk of recurrence in the group with pN0M0 lung adenocarcinoma.

Prospective, randomized, cross-over pilot study of the effects of Rikkunshito, a Japanese traditional herbal medicine, on anorexia and plasma-acylated ghrelin levels in lung cancer patients undergoing cisplatin-based chemotherapy.

Purpose Anorexia induced by cytotoxic chemotherapy on delayed phase is a highly frequent adverse event. We aimed to determine the effects of rikkunshito (RKT) on chemotherapy-induced anorexia (CIA) in patients with lung cancer. Methods This prospective, randomized, cross-over pilot trial included 40 lung cancer patients scheduled to undergo cisplatin-based chemotherapy and randomized to either a group given RKT 7.5 g/day for 14 days (Group A, N = 20) or not (Group B, N = 20), then the treatments were switched. All patients received dexamethasone, palonosetron hydrochloride and aprepitant regardless of group assignment. Rescue drugs were allowed as required. The primary and key secondary endpoints were changes in caloric intake and in plasma acylated ghrelin (AG) levels, respectively. Average daily caloric intake during days 3 to 5 was compared with that on day 1 of each course. Results The primary and key secondary endpoints were analyzed in 31 patients (per protocol population) completing the study. Reduction rate of caloric intake was lower in RKT, than in control courses (18% vs. 25%, P = 0.025). Plasma AG levels significantly declined between days 1 and 3 in RKT (12.3 vs. 7.5 fmol/mL, P < 0.001) and control (10.8 vs. 8.6 fmol/mL, P < 0.001) courses. However, those obviously increased to 8.5 fmol/mL (P = 0.025) by day 5 in RKT course but not in control course (7.7 fmol/mL, P = 0.28). Conclusions Rikkunshito could mitigate CIA and ameliorate plasma AG levels during the delayed phase of CDDP-based chemotherapy in lung cancer patients. Clinical trial registration numbers: UMIN000010748.