Rapid intraoperative Ki-67 immunohistochemistry for lung cancer using non-contact alternating current electric field mixing.

OBJECTIVES: Locoregional recurrence of non-small cell lung cancer (NSCLC) occurs even among patients with stage I disease, as a result of tumor proliferative activity. The aim of this study was to evaluate the clinical reliability of a new rapid immunohistochemistry (IHC) technique for assessing malignant potential through detection of tumoral Ki-67 expression. MATERIALS AND METHODS: The rapid IHC method uses non-contact alternating current (AC) mixing to achieve more rapid/stable staining within 20 min during surgery. First, to investigate the association between clinical outcomes and tumoral Ki-67 labeling with rapid IHC, 21 pairs of surgical patients treated between 2012 and 2020 for pStage IA1-3 NSCLC with/without recurrence were retrospectively reviewed. Second, 40 frozen section (FS) samples in patients with NSCLC for whom radical surgery was planned between April 2021 and February 2022 were deemed eligible for comparison of the clinical performance of conventional IHC and intraoperative rapid Ki-67 IHC with FS. RESULTS: Detection of tumoral Ki-67 expression using rapid IHC with formalin-fixed, paraffin-embedded (FFPE) blocks was significantly associated with clinical outcomes in R0 pStage IA NSCLC surgical patients, including overall and recurrence-free survival (P = 0.0043 and P < 0.0001, respectively). Levels of Ki-67 expression among resectable NSCLC patients detected using rapid IHC with FS significantly correlated with those detected using conventional FFPE-IHC (p < 0.001). An intraoperative cut-off of > 7.5 % tumor cell Ki-67 positivity accurately predicted pathological stage more advanced than IA3 [P = 0.0185, Odds ratio = 20.477, 95 % confidence interval (CI): 1.660-252.55]. CONCLUSION: Rapid Ki-67 IHC with AC mixing could potentially serve as a clinical tool for intraoperative determination of tumor malignancy status. The present study suggests that segmentectomy for early small NSCLCs is oncologically safe and a reasonable alternative to lobectomy, but only when there is adequate intraoperative selection for primary tumors with low-grade malignancy, which could be verified using intraoperative rapid Ki-67 IHC with FS.

New PET/CT criterion for predicting lymph node metastasis in resectable advanced (stage IB-III) lung cancer: The standard uptake values ratio of ipsilateral/contralateral hilar nodes.

BACKGROUND: The aim of the present study was to use surgical and histological results to develop a simple noninvasive technique to improve nodal staging using preoperative PET/CT in patients with resectable lung cancer. METHODS: Preoperative PET/CT findings (pStage IB-III 182 patients) and pathological diagnoses after surgical resection were evaluated. Using PET/CT images to determine the standardized uptake value (SUV) ratio, the SUVmax of a contralateral hilar lymph node (on the side of the chest opposite to the primary tumor) was measured simultaneously. The I/C-SUV ratio was calculated as ipsilateral hilar node SUV/contralateral hilar node SUV. Receiver operating characteristic (ROC) curves were then used to analyze those data. RESULTS: Based on ROC analyses, the cutoff I/C-SUV ratio for diagnosis of lymph node metastasis was 1.34. With a tumor ipsilateral lymph node SUVmax ≥2.5, an IC-SUV ratio ≥1.34 had the highest accuracy for predicting N1/N2 metastasis; the sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) and accuracy of nodal staging were 60.66, 85.11, 84.09, 62.5 and 71.29%, respectively. CONCLUSIONS: When diagnosing nodal stage, a lymph node I/C-SUV ratio ≥1.34 can be an effective criterion for determining surgical indications in advanced lung cancer.

Using CT to evaluate mediastinal great vein invasion by thymic epithelial tumors: measurement of the interface between the tumor and neighboring structures.

OBJECTIVES: For thymic epithelial tumors, simple contact with adjacent structures does not necessarily mean invasion. The purpose of our study was to develop a simple noninvasive technique for evaluating organ invasion using routine pretreatment computed tomography (CT). METHODS: This retrospective study analyzed the pathological reports on 95 mediastinal resections performed between January 2003 and June 2020. Using CT images, the length of the interface between the primary tumor and neighboring structures (arch distance; Adist) and maximum tumor diameter (Dmax) was measured, after which Adist/Dmax (A/D) ratios were calculated. Receiver operating characteristic (ROC) curves were used to analyze the Adist and A/D ratios. RESULTS: An Adist cut-off of 37.5 mm best distinguished between invaded and non-invaded mediastinal great veins based on ROC curves. When Adist > 37.5 mm was used for diagnosis of invasion of the brachiocephalic vein (BCV) or superior vena cava (SVC), the sensitivity, specificity, positive predictive value, negative predictive value, accuracy, and area under the ROC curve for diagnosis of invasion were 61.9%, 92.5%, 81.25%, 82.2%, 81.97%, and 0.76429, respectively. Moreover, there were significant differences between BCV/SVC Adist > 37.5 mm and ≤ 37.5 mm for 10-year relapse-free survival and 10-year overall survival (p < 0.01). CONCLUSIONS: When diagnosing invasion of the mediastinal great veins based on Adist > 37.5 mm, we achieved a higher performance level than the conventional criteria such as irregular interface with an absence of the fat layer. Measurement of Adist is a simple noninvasive technique for evaluating invasion using CT. Key Points • Simple contact between the primary tumor and adjacent structures on CT does not indicate direct invasion. • Using CT images, the length of the interface between the primary tumor and neighboring structures (arch distance; Adist) is a simple noninvasive technique for evaluating invasion. • Adist > 37.5 mm can be a supportive tool to identify invaded mediastinal great veins and surgical indications for T3 and T4 invasion by thymic epithelial tumors.

Harmonization across programmed death ligand 1 (PD-L1) assays for lung cancer by immunohistochemistry using noncontact alternating current electric field mixing.

BACKGROUND: Immune checkpoint inhibitors (ICIs) are a promising advance in the treatment of patients with lung cancer. However, each ICI has been tested with an independently designed companion diagnostic assay that is based on a unique antibody. Consequently, the different trial-validated programmed death ligand 1 (PD-L1) immunohistochemistry (IHC) assays should not be considered interchangeable. Our aim was to compare the performance of each available PD-L1 antibody for its ability to accurately measure PD-L1 expression and to investigate the possibility of harmonization across antibodies through the use of a new rapid IHC system, which uses noncontact alternating current (AC) mixing to achieve more stable staining. METHODS: First, 58 resected non-small cell lung cancer (NSCLC) specimens were stained using three PD-L1 IHC assays (28-8, SP142, and SP263) to assess the harmonization achieved with AC mixing IHC. Second, specimens from 27 patients receiving ICIs for postoperative recurrent NSCLC were stained using the same IHC method to compare the clinical performance of ICIs to PD-L1 scores. All patients received a tumor proportion score (TPS) with the 22C3 companion diagnostic test. RESULTS: Better staining was achieved with the new AC mixing IHC method than the conventional IHC in PD-L1-positive cases, and the interchangeability of some combinations of assays was increased in PD-L1-positive. In addition, AC mixing IHC provided more appropriate overall response rates for ICIs in all assays. CONCLUSIONS: Stable PD-L1 IHC driven by AC mixing helped to improve TPS scoring and patient selection for ICIs through interchangeable assays.

Clinical benefits of adjuvant chemotherapy with carboplatin and gemcitabine in patients with non-small cell lung cancer: a single-center retrospective study.

PURPOSE: In cases of non-small cell lung cancer (NSCLC), surgery remains the best option for cure, but surgery is of benefit only when the disease is localized. Although adjuvant chemotherapy reportedly has a significant beneficial effect on survival, the benefit of a carboplatin (CBDCA) regimen is unclear. We therefore investigated the efficacy and tolerability of CBDCA (area under the curve 5) plus gemcitabine (GEM, 1000 mg/m2) as adjuvant chemotherapy. METHODS: A total of 82 pStage IB-IIIA NSCLC patients who had undergone complete resection and received adjuvant chemotherapy were analyzed retrospectively. Among them, 65 patients received CBDCA + GEM and 17 received CDDP + VNR. Propensity score analysis generated 17 matched pairs of both groups. RESULTS: Sixty-five patients received CBDCA + GEM. Their 5-year relapse-free survival (RFS) and overall survival were 47.8% (median, 52.5 months) and 76.9% (median, 90.1 months), respectively. Toxicities, which included neutropenia, nausea/anorexia, fatigue, and vasculitis, were significantly milder than with CDDP + VNR. There were no significant differences in RFS between CBDCA + GEM and CDDP + VNR (p = 0.079) after matching for age, performance status, and pStage. CONCLUSION: CBDCA + GEM was effective and well tolerated as adjuvant chemotherapy, with a manageable toxicity profile.

Intraoperative diagnosis of lymph node metastasis during segmentectomy for non-small cell lung cancer by rapid immunohistochemistry using noncontact alternating current electric field mixing.

BACKGROUND: Although lobectomy is considered the standard surgery for any non-small cell lung cancer (NSCLC), recent evidence indicates that for early NSCLCs segmentectomy may be equally effective. For segmentectomy to be oncologically safe, however, adequate intraoperative lymph node staging is essential. The aim of this study was to compare the results of a new rapid-IHC system to the HE analysis for intraoperative nodal diagnosis in lung cancer patients considered for segmentectomy. METHODS: This retrospective study analyzed the pathological reports from NSCLC resections over a six-year period between 2014 and 2020. Using a new device for rapid-IHC, we applied a high-voltage, low-frequency alternating current (AC) field, which mixes the antipancytokeratin antibody as the voltage is switched on/off. Rapid-IHC can provide a nodal diagnosis within 20 minutes. RESULTS: Frozen sections from 106 resected lymph nodes from 70 patients were intraoperatively evaluated for metastasis. Of those, five nodes were deemed positive based on both HE staining and rapid-IHC. In addition, rapid-IHC alone detected isolated tumor cells in one hilar lymph node. Three cStage IA patients with nodal metastasis detected with HE staining and rapid-IHC received complete lobectomies. Five-year relapse-free survival and overall survival among patients receiving segmentectomy with rapid-IHC were 88.77% and 88.79%, respectively. CONCLUSIONS: Rapid-IHC driven by AC mixing is simple, highly accurate, and preserves nodal tissue for subsequent tests. This system can be used effectively for intraoperative nodal diagnosis. Rapid immunohistochemistry based on alternating-current field mixing (completed within 20 minutes) is simple and highly accurate. This system will assist clinicians when making intraoperative diagnoses of lymph node metastasis and deciding upon the appropriate surgical procedure in segmentectomy for lung cancer. KEY POINTS: SIGNIFICANT FINDINGS OF THE STUDY: Rapid immunohistochemistry driven by alternating-current field mixing (completed within 20 minutes intraoperatively) is simple, highly accurate, and preserves lymph node tissue for subsequent pathological examination, including molecular assessments. WHAT THIS STUDY ADDS: Segmentectomy for lung cancer is oncologically safe, but only when there is adequate intraoperative node staging. Rapid immunohistochemistry will assist clinicians when making intraoperative nodal diagnoses.

Effect of lidocaine cream analgesia for chest drain tube removal after video-assisted thoracoscopic surgery for lung cancer: a randomized clinical trial.

BACKGROUND AND OBJECTIVES: Pain management makes an important contribution to good respiratory care and early recovery after thoracic surgery. Although the development of video-assisted thoracoscopic surgery (VATS) has led to improved patient outcomes, chest tube removal could be distressful experience for many patients. The aim of this trial was to test whether the addition of lidocaine cream would have a significant impact on the pain treatment during chest tube removal from patients who had undergone VATS for lung cancer. METHODS: This clinical trial was a double-blind randomized study. Forty patients with histologically confirmed lung cancer amenable to lobectomy/segmentectomy were enrolled. All patients had standard perioperative care. Patients were randomly assigned to receive either epidural anesthesia plus placebo cream (placebo, Group P) or epidural anesthesia plus 7% lidocaine cream cutaneously around the chest tube insertion site and on the skin over the tube's course 20 min (Group L) before chest drain removal. RESULTS: Visual analog scale (VAS) scores were higher in Group P (median 5, IQR, 3.25-8) than in Group L (median 2, IQR, 1-3). Pain intensities measured using a PainVision system were also higher in Group P (median 296.7, IQR, 216.9-563.5) than Group L (median 41.2, IQR, 11.8-97.0). VAS scores and the pain intensity associated with chest drain removal were significantly lower in Group L than Group P (p=0.0002 vs p<0.0001). CONCLUSION: Analgesia using lidocaine cream is a very simple way to reduce the pain of chest tube removal after VATS. TRIAL REGISTRATION NUMBER: UMIN000013824.

Lung Cancer Surgery in Partial Anomalous Pulmonary Venous Connection Patients.

We report pulmonary resections for lung cancers in 2 patients with partial anomalous pulmonary venous connection (PAPVC) identified preoperatively. In case 1, right upper lobectomy was performed as the definitive operation for both lung cancer and PAPVC in the same lobe. In case 2, because lung cancer and PAPVC existed in different lobes, cardiac catheterization was performed to evaluate the need for correction of the PAPVC. Then, left lower lobectomy was safely performed without correcting the PAPVC located in the left upper lobe. The treatment plan for patients with PAPVC who require pulmonary resection should be carefully considered.

Rapid Immunohistochemistry With Thyroid Transcription Factor-1 for Pulmonary Adenocarcinoma.

BACKGROUND: Intraoperative pathologic diagnosis of solitary pulmonary tumors to differentiate between metastatic and primary lung cancer is extremely important to determine the appropriate range of excision. Accurate intraoperative pathologic evaluation may be often difficult, however, and needs additional immunohistochemical (IHC) evaluation to support the diagnosis. Although conventional IHC is a powerful tool for diagnosis, its clinical use is limited intraoperatively because of time constraints. To address this issue, we developed a device that enables complete and rapid IHC (R-IHC) analyses within 20 minutes. We aimed to evaluate the discriminative ability of the R-IHC with anti-thyroid transcription factor-1 (TTF-1) antibody, which is a highly specific IHC marker for primary lung adenocarcinoma. METHODS: A total of 61 pulmonary tumors that were resected at our institute from May 2011 to September 2013 were retrospectively examined. The samples were sectioned, labeled with anti-TTF-1 antibody using the R-IHC method, and pathologically evaluated. The standard used for evaluation was conventional IHC with TTF-1. RESULTS: With the R-IHC procedure, analyses were completed within 20 minutes, with a diagnostic accuracy of 96.7% (59 of 61). Among the 47 primary lung adenocarcinomas, the R-IHC detected 31 (66%) tumors that were positive for TTF-1, with a positive predictive value of 100% (31 of 31). CONCLUSIONS: Our newly developed method of R-IHC with anti-TTF-1 antibody was useful for diagnosing and differentiation of solitary pulmonary tumors. This technology may prove to be an important supplement to standard intraoperative pathologic diagnosis in routine practice.

Management of Intersegmental Plane on Pulmonary Segmentectomy Concerning Postoperative Complications.

BACKGROUND: For primary lung cancer, anatomic pulmonary segmentectomy may have a functional advantage over lobectomy; however, persistent air leak or delayed pneumothorax after segmentectomy is prevalent and increases surgical morbidity. To prevent pulmonary complications after pulmonary segmentectomy, we used 2 methods for the involved intersegmental plane: coverage using polyglycolic acid mesh and fibrin glue (mesh cover) or closing it by suturing the pleural edge (pleural suture). We aimed to compare postoperative pulmonary function and complications between the 2 groups. METHODS: A total of 133 patients who underwent pulmonary segmentectomy for stage IA non-small cell lung cancer were analyzed retrospectively. A pulmonary function test, including vital capacity and forced expiratory volume in 1 second, was performed preoperatively and at 1 and 6 months postoperatively. Propensity score analysis generated 2 matched pairs of 46 patients in the pleural suture and mesh cover groups. RESULTS: In each group, there was no significant difference in the recovery rate of vital capacity and forced expiratory volume in 1 second at 1 and 6 months postoperatively. Compared with the pleural suture group, the mesh cover group had higher incidence of prolonged air leak (8.7% versus 0%; p = 0.042), delayed pneumothorax (10.9% versus 2.2%; p = 0.051). On logistic regression analysis, management of intersegmental plane by either mesh cover or pleural suture was the only independent factor related to pulmonary complications (prolonged air leak or delayed pneumothorax) after pulmonary segmentectomy (odds ratio: 5.26, p = 0.047; odds ratio: 13.39, p = 0.018, respectively). CONCLUSIONS: Pleural suturing of the involved intersegmental plane during pulmonary segmentectomy appeared to be an acceptable method to reduce postoperative pulmonary complications.

An extremely rare case report of surgery of lung cancer with the absence of azygos vein.

In thoracic surgery, we occasionally encounter vessel anomalies. We herein report an extremely rare surgical case with the absence of the azygos vein. Mediastinal vascular abnormalities are said to be rare. The etiology of vascular abnormalities of the whole body, including the chest is known gene mutations, hormone abnormalities, infection, and trauma. But, many causes have been unknown. In thoracic surgery field, there is some reports and literature about pulmonary arteriovenous malformation, pulmonary sequestration, and partial anomalous pulmonary venous return. But reports about absence of azygos vein are not much. It is considered that it is less likely to become a problem in clinical. As we discussed in the paper, it will be more interesting if the association with PLSVC reveals from more cases. A 58-year-old man was admitted to our hospital in order to undergo operation for the treatment of lung cancer. We detected absence of the azygos vein by preoperative computed tomography (CT). Furthermore, three-dimensional angiography (3D-angiography) showed that the right superior intercostal vein and hemiazygos vein in the left thoracic cavity were more developed than usual. Then, we discuss the key points during surgery and suggest the potential association between the absence of the azygos vein and a persistent left superior vena cava (PLSVC).

Thymic carcinoma with myasthenia gravis: Two case reports.

INTRODUCTION: Myasthenia gravis (MG) has been reported to correlate with earlier-stage thymoma, and theoretically does not accompany thymic carcinoma. However, we encountered two cases of thymic carcinoma with MG. PRESENTATION OF CASES: Case 1 involved a 54-year-old man who had been diagnosed with MG based on symptoms and detection of anti-acetylcholine receptor antibody (ARAB). Computed tomography (CT) revealed an anterior mediastinal tumor 30mm in diameter. Prednisolone (PSL) and tacrolimus were administered without surgery at that time. Six years after diagnosis of MG, he was admitted to our hospital and underwent extended thymectomy. Pathological examination revealed type B2-B3 thymoma according to World Health Organization criteria, comprising 80% of the tumor with small cell carcinoma as 20%. Case 2 involved a 51-year-old woman. She had been diagnosed with MG based on eyelid ptosis and detection of ARAB. Ten years after diagnosis of MG, diaphragm elevation was detected on chest X-ray. CT revealed an anterior mediastinal tumor, 47mm in diameter. We suspected tumor invasion to the right phrenic nerve, right atrium, and superior vena cava. We therefore performed extended thymectomy after preoperative radiotherapy (40Gy). Pathological examination revealed squamous cell carcinoma. DISCUSSION: Most cases of thymic carcinomas appear to arise de novo, but appearance in thymomas has been described. In both our cases, MG was treated with pharmacotherapy alone without extended thymectomy, and thymic carcinoma was considered to have developed from the thymoma during long-term follow-up. CONCLUSION: Thymic carcinoma can accompany MG.

Pulmonary Resection for Metastatic Gastric Cancer.

BACKGROUND: Pulmonary metastasectomy has come to be recognized as an effective treatment for selected patients with some malignancies. On the other hand, the role of pulmonary metastasectomy for gastric cancer is still unknown. Metastasectomy is rarely indicated in cases of pulmonary metastasis from gastric cancer, because in most cases, the metastasis occurs in the form of lymphangitic carcinomatosis and the lesions are numerous. The purpose of this study was to determine the surgical outcomes and prognostic factors for survival after pulmonary metastasectomy. METHODS: From 1985 to 2012, 10 patients underwent pulmonary metastasectomy for gastric cancer at Saitama Cancer Center, Japan. The overall survival rate was examined by the Kaplan-Meier method and univariate analysis was carried out to identify prognostic factors. RESULTS: The overall 3-year survival rate was 30.0 %. The median follow-up period was 26.8 months (range, 6.5-96.6) after the pulmonary metastasectomy. Univariate analysis revealed an advanced pathological stage of the gastric cancer and occurrence of extrapulmonary metastasis before the pulmonary metastasectomy as unfavorable prognostic factors. CONCLUSION: Pulmonary metastasectomy should be considered in selected patients with lung metastasis from gastric cancer. An advanced pathological stage of gastric cancer and occurrence of extrapulmonary metastasis before the pulmonary metastasectomy are unfavorable prognostic factors.

Abnormal branch of right pulmonary artery (A7): a case report and literature review.

In thoracic surgery, anatomic variations of pulmonary artery increase the risks for vessel injury and critical mistakes during pulmonary artery resection. We report a case of lung cancer with an extremely rare branch, a mediastinal A7 pulmonary artery. Some case reports of the mediastinal pulmonary artery exist until now. However, to the best of our knowledge, this is the first case of a medial basal segmental artery (from the following, it is referred to as A7) branching directly from main pulmonary artery in the literature. Therefore, there is no report that showed three-dimensional computed tomography (3D-CT) and operative findings. So, these information is very useful for thoracic surgeon. A 67-year-old man was admitted to our hospital in order to undergo operation for the treatment of lung cancer. We detected the anomalies preoperatively by 3D-CT. The 3D-CT shows the A7 pulmonary artery branches from the right main pulmonary artery directly. According to previous literature, the cases of a single branch from main pulmonary artery to lower lobe are only five cases. And, the only two of them are right side including our case. In spite of an extremely rare case, we were able to successfully perform a right middle lobectomy because the information obtained from the 3D-CT findings was sufficiently understood preoperatively.

Case report of two patients having successful surgery for lung cancer after treatment for Grade 2 radiation pneumonitis.

INTRODUCTION: Surgery for locally advanced lung cancer is carried out following chemoradiotherapy. However, there are no reports clarifying what the effects on the subsequent prognosis are when surgery is carried out in cases with radiation pneumonitis. In this paper, we report on 2 cases of non-small cell lung cancer with Grade 2 radiation pneumonitis after induction chemoradiotherapy, in which we were able to safely perform radical surgery subsequent to the treatment for pneumonia. PRESENTATION OF CASES: Case 1 was a 68-year-old male with a diagnosis of squamous cell lung cancer cT2aN2M0, Stage IIIA. Sixty days after completion of the radiotherapy, Grade 2 radiation pneumonitis was diagnosed. After administration of predonine, and upon checking that the radiation pneumonitis had improved, radical surgery was performed. Case 2 was a 63-year-old male. He was diagnosed with squamous cell lung cancer cT2bN1M0, Stage IIB. One hundred and twenty days after completion of the radiotherapy, he was diagnosed with Grade 2 radiation pneumonitis. After administration of predonine, the symptoms disappeared, and radical surgery was performed. In both cases, the postoperative course was favorable, without complications, and the patients were discharged. CONCLUSION: Surgery for lung cancer on patients with Grade 2 radiation pneumonitis should be deferred until the patients complete steroid therapy, and the clinical pneumonitis is cured. Moreover, it is believed that it is important to remove the resolved radiation pneumonitis without leaving any residual areas and not to cut into any areas of active radiation pneumonitis as much as possible.

The importance of determining surgical indications in cases of lung cancer and interstitial pneumonia with multiple intrapulmonary lymph nodes.

INTRODUCTION: When considering treatment for pulmonary cancer complicated by interstitial pneumonia, the greatest problem is acute exacerbation. We report two cases of pulmonary cancer complicated by interstitial pneumonia in which multiple intrapulmonary lymph nodes were noted. CASE PRESENTATIONS: Cases 1 and 2 were 76- and 62-year-old males, respectively. Both cases were diagnosed as pulmonary cancer complicated by interstitial pneumonia, and upon chest CT, it was noted that, in addition to the primary lesions, there were multiple nodule shadows under the pleura in the lung lobe, which required identification in order to rule out lung metastasis. In Case 1, the pulmonary nodules were first resected during surgery and a swift diagnosis was made, determining them to be intrapulmonary lymph nodes, which were then operated on curatively. In Case 2, the patient underwent thoracoscopic observation during surgery, the shadows were diagnosed visually as intrapulmonary lymph nodes, and curative surgery was implemented. DISCUSSION AND CONCLUSIONS: The greatest problem in treating pulmonary cancer complicated with interstitial pneumonia is acute exacerbation, wherein, in the absence of any surgical indications, alternative treatment is limited. Thus, contra-indicating surgery for a patient due to a diagnosis of metastasis within the lungs, based only on nodule images, should be avoided. If nodules are noted in the area of the pleura, the possibility exists that these could be intrapulmonary lymph nodes, along with metastasis within the lung, and thoracoscopic surgery should be implemented proactively while keeping these in mind.

Development of a New Magnetometer for Sentinel Lymph Node Mapping Designed for Video-Assisted Thoracic Surgery in Non-Small Cell Lung Cancer.

BACKGROUND: We previously developed a method for sentinel lymph node (SLN) mapping in non-small cell lung cancer (NSCLC), based on the magnetic force produced by a magnetite tracer already approved for use as a contrast material for magnetic resonance imaging. However, it is difficult to use that technique with video-assisted thoracic surgery (VATS) because the sensing element of the magnetometer is large and thick. The purpose of the present study was to develop a smaller, thinner VATS-compatible magnetometer. METHODS: The tracer employed was Ferucarbotran, a colloidal solution of superparamagnetic iron oxide coated with carbodextran. Fifteen patients with clinical stage I NSCLC were enrolled, and each received 1.6 mL of Ferucarbotran, injected intraoperatively at 5 points around the tumor. The magnetic force within the sampling lymph nodes was measured using the new VATS-compatible magnetometer. RESULTS: SLNs were detected in 11 (73.3%) of the 15 patients using the VATS-compatible magnetometer. The average number of SLNs identified per patient was 1.8 (range 0-4). No complications related to the SLN detection method were observed. CONCLUSIONS: The new VATS-compatible magnetometer appears to have substantial advantages over techniques using a radioisotope and our earlier magnetometer, as it can be inserted through the small VATS port site.

C-reactive protein inhibits expression of N-cadherin and ZEB-1 in murine colon adenocarcinoma.

Epithelial-to-mesenchymal transition (EMT) is thought to play a key role in cancer cell invasion and metastasis. We previously demonstrated that cancer cell migration is inhibited by C-reactive protein (CRP), which is widely used as a biomarker of inflammation, though its functions are not fully understood. In the present study, we evaluated the effect of CRP on cancer cell migration and expression of mesenchymal and epithelial markers of EMT and of related transcription factors. MCA-38 murine colon adenocarcinoma cells were subcutaneously inoculated into the backs of C57BL/6 mice, which also received 1 µg of recombinant mouse CRP or vehicle (phosphate-buffered saline) subcutaneously every 3 days for 4 weeks. Thereafter, the mice were sacrificed for evaluation using quantitative real-time polymerase chain reaction (PCR) and immunohistochemistry. There was no statistical difference in tumor size between the control and CRP groups, but CRP dose-dependently inhibited MCA-38 cell migration. PCR analysis confirmed that CRP suppresses expression of N-cadherin (p < 0.01), a mesenchymal marker of EMT, and ZEB-1, an EMT-related transcription factor (p < 0.01). These findings suggest that CRP inhibits EMT in a MCA-38 tumor-bearing mouse model. CRP may thus be a potentially useful tool for preventing cancer progression through suppression of EMT.

[Perioperative management for surgery against lung cancer in patients with receiving coronary stent implantation].

Increasing in patients with cardiac disease, it is estimated that the patients with receiving coronary artery stents implantation occur frequently at the time of surgery against lung cancer. However, the anti-thrombotic therapy in perioperative period is not well established. We reviewed the medical records of 934 patients who underwent pulmonary resection for primary lung cancer in our institute from March 1997 to November 2014. The cardiac disease was observed 101 patients, including 9 patients were implanted bare-metal stents( BMS) and 6 patients were done drug-eluting stents( DES). The interval to surgery after stent implantation was almost over 1-month in BMS-group (median:18 months) and more than 1-year in DES-group( median:22.5 months). The anti-thrombotic therapy was interrupted less than 14-days in almost cases. The patients with receiving coronary artery stents implantation expected to be increased more in future, perioperative anti-thrombotic management protocols must be established.

Strong expression of cyclin B2 mRNA correlates with a poor prognosis in patients with non-small cell lung cancer.

Cyclin family proteins act in association with cyclin-dependent kinases (CDK) at cell cycle checkpoints to regulate the eukaryotic cell cycle. CyclinB2 contributes to G2/M transition by activating CDK1 kinase, and cyclin B2 inhibition induces cell cycle arrest. CyclinB2 is overexpressed in various human tumors, though the relationship between cyclin B2 expression and the clinicopathological characteristics of lung cancer and patient prognosis is not well understood. In the present study, therefore, we investigated the relationship between cyclin B2 mRNA expression and the prognosis of patients with non-small cell lung cancer (NSCLC). We used semiquantitative real-time reverse transcription polymerase chain reaction to assess the expression of cyclin B2 mRNA in tumor samples from 79 patients with NSCLC. We then correlated the cyclin B2 mRNA levels with clinicopathological factors. We also used immunohistochemical staining to determine the localization of expressed cyclin B2. The 5-year overall survival rates among patients with adenocarcinoma of lung expressing lower levels of cyclin B2 mRNA were significantly better than the corresponding rates among patients expressing higher levels (p = 0.004). Multivariate Cox proportional hazard analyses revealed that gender ((hazard ratio (HR), 9.81; p = 0.044)), n2 (HR, 146.26; p ≤ 0.001), and cyclin B2 mRNA high (HR, 7.21; p = 0.021) were independent factors affecting the 5-year overall survival rates. However, there was no significance in the 5-year overall survival rates among the patients with squamous cell carcinoma between expressing lower and higher level of cyclin B2 mRNA. Stronger expression of cyclin B2 mRNA in tumor cells is an independent predictor of a poor prognosis in patients with adenocarcinoma of lung.