Cone-Beam Computed Tomography-Guided Marking of Small Pulmonary Nodules with Surgical Clips.

BACKGROUND: Preoperative computed tomography-guided marking can help identify small non-palpable pulmonary nodules during surgery. However, this technique is associated with the risk of air embolism. We retrospectively evaluated whether small pulmonary nodules could be intraoperatively localized using cone-beam computed tomography (CBCT). METHODS: A hybrid operating room permitting stable lateral positioning and scanning from the pulmonary apex to the base was used in all patients. CBCT images were obtained using a 10-s protocol with 180º rotation of the C-arm flat panel detector around the patient. Clips were placed on the visceral pleura to help guide pulmonary nodule localization. Partial pulmonary resection was performed using video-assisted thoracoscopic surgery at the predicted nodule site. RESULTS: Between July 2013 and June 2019, 132 patients with 145 lesions underwent this procedure at our center. The detection rate of lesions on CBCT was 100%. The pathological diagnoses were primary lung cancer, metastatic pulmonary tumors, and benign lesions. The average consolidation-to-tumor ratio was 0.65 for all nodules, with ratios of 0.33, 0.96, and 0.70 for primary lung cancer, metastatic pulmonary tumors, and benign lesions, respectively. No complications related to this localization method were observed. CONCLUSIONS: CBCT-guided intraoperative localization is safe and feasible for non-palpable small pulmonary nodules. This technique may eliminate the risk of serious complications such as air embolism.

Utility of non-contrast-enhanced magnetic resonance imaging in predicting preoperative clinical stage and prognosis in patients with thymic epithelial tumor.

PURPOSE: The purpose of this study was to find useful imaging features on non-contrast-enhanced magnetic resonance imaging (MRI) that can divide patients with thymic epithelial tumor (TET) into clinical stage I-II and III-IV groups under assumption that contrast media are contraindicated. MATERIALS AND METHODS: This retrospective study included 106 patients (median age, 60 years; range, 27-82 years; 62 women) with surgically resected TET who underwent MRI between August 1986 and July 2015. All cases were classified according to the 2015 WHO classification and staged using the eighth edition of the TNM system. Two radiologists independently evaluated 14 categories of MRI findings; the findings in patients with stage I-II were compared with those of patients with stage III-IV using a logistic regression model. Disease-specific survival associated with significant findings was calculated using the Kaplan-Meier method. RESULTS: Univariate analysis showed that stage III-IV patients were more likely to have tumors with an irregular contour, heterogeneity on T1WI, low-signal intensity on T2WI, irregular border with lung, findings of great vessel invasion (GVI) (hereafter, GVI sign), pericardial thickening/nodule, and lymphadenopathy (all, P < 0.01). On multivariable analysis, only two findings, irregular border between tumor and lung (odds ratio [OR], 272.8; 95% CI 26.6-2794.1; P < 0.001) and positive GVI sign (OR, 49.3; 95% CI 4.5-539.8; P = 0.001) remained statistically significant. Patients with one or both features had significantly worse survival (log-rank test, P < 0.001). CONCLUSION: For patients with TET who are unable to receive contrast for preoperative staging, the two image findings of an irregular border between tumor and lung and the positive GVI sign on non-contrast-enhanced MRI could be helpful in determining stage III-IV disease which is associated with a worse survival.

Initial Experience with Robotic Gastrectomy in Patients with Gastric Cancer: An Assessment of Short-Term Surgical Outcomes.

Robotic gastrectomy (RG) is an alternative minimally invasive surgical technique that has gradually come into use for the treatment of gastric cancer (GC). This study aimed to assess the feasibility and safety of RG for the treatment of GC. We retrospectively reviewed the use of RG in 47 patients with GC, and clinicopathological features and surgical outcomes were evaluated. The median age and body mass index of the patients were 68 years and 21.9 kg/m2, respectively. Distal gastrectomy, total gastrectomy, and proximal gastrectomy were performed in 39 (83.0%), 5 (10.6%), and 3 (6.4%) patients, respectively. The median operative time was 354 (256- 603) min. None of the operations were converted to open or laparoscopic procedures. The median blood loss was 15 (2-350) ml. None of the patients required blood transfusion. The mean number of resected lymph nodes was 43 (7-93). The median duration of postoperative hospital stay was 13 (9-37) days. Approximately 4.3% and 2.1% of the patients had anastomotic leakage and pancreatic fistula, respectively. One (2.1%) patient had Clavien-Dindo classification grade IIIa surgical complication (anastomotic leakage). No treatment-related deaths were observed. These findings suggest that RG might be a safe and feasible procedure for the treatment of GC.

Temporary airway stenting for giant anterior mediastinal tumor biopsy: Two case reports.

INTRODUCTION: When the management of an anterior mediastinal tumor requires general anesthesia, airway narrowing and obstruction may occur secondary to muscle relaxation. PRESENTATION OF CASES: Two men (ages, 15 and 36 years) presented with a giant anterior mediastinal tumor and central airway obstruction. We used Dumon stents to effectively secure the airway in both patients. After chemotherapy, stent removal was safely performed in each case because the tumor was substantially smaller. DISCUSSION: Dumon stents effectively secured the airway. These stents were easily removed after chemotherapy without severe complications. CONCLUSION: Temporary stenting is useful in patients with a giant anterior mediastinal tumor who require general anesthesia.

Lung function in the late postoperative phase and influencing factors in patients undergoing pulmonary lobectomy.

BACKGROUND: Lung function in the late postoperative phase after pulmonary lobectomy is insufficiently characterized. This study aimed to appraise lung function in the late postoperative phase according to vital capacity (VC) and forced expiratory volume in 1 second (FEV1) in patients who underwent pulmonary lobectomy. METHODS: Pre- and postoperative VC and FEV1 were reviewed in 112 patients who underwent pulmonary lobectomy. Postoperative lung volume was assessed >1 year after surgery. Postoperative decreases in VC and FEV1 were compared with preoperative predicted values among patients who underwent resection of specific lobe. Determinants effecting a decrease in lung function were also investigated. RESULTS: A mean postoperative decreased VC of 10.5%±1.8% was recorded in patients who underwent right upper lobectomy (RU), 7.2%±1.5% for right middle lobectomy (RM), 14.3%±2.3% for right lower lobectomy (RL), 16.6%±3.0% for left upper lobectomy (LU), and 14.7%±2.5% for left lower lobectomy (LL). Corresponding FEV1 values were 14.8%±1.8% for RU, 11.9%±4.0% for RM, 14.9%±2.3% for RL, 17.9%±2.9% for LU, and 15.1%±2.4% for LL. The actual decreasing rate of VC was overestimated in patients who underwent RU, RL, LU, and LL. In contrast, FEV1 was overestimated only in patients who underwent RL and LL. Patients with chronic obstructive pulmonary disease (COPD) exhibited significantly better preservation of FEV1. CONCLUSIONS: Patients scheduled for RL and LL, or those with COPD, appeared to exhibit preserved lung function in the late postoperative phase after pulmonary lobectomy.

Periostin Expression in Non-Small Cell Lung Cancer: Clinical Significance.

Periostin is an extracellular matrix N-glycoprotein that is a major constituent of the desmoplastic stroma around solid tumors. Periostin promotes tumor invasion and metastasis via epithelial-mesenchymal transition. The aims of this study were to evaluate periostin expression immunohistochemically and quantitatively in patients with non-small cell lung cancer (NSCLC) and to assess any associations with clinical features and prognosis. A total of 184 specimens of NSCLC tissue were investigated, including 134 adenocarcinomas, 39 squamous cell carcinomas, and 11 other histologic subtypes. The intra-tumoral periostin expression area in each captured field was calculated using the image processing integration software WinROOF. The mean periostin expression score was classified as high or low by the median value of its expression area. Univariate analysis demonstrated that gender, tumor size, T status, N status, stage, histologic type, smoking habits, percent vital capacity, 1% forced expiratory volume, and pleural invasion were each significantly associated with periostin scores. Multivariate analysis revealed that high periostin expression score was an independent prognostic factor significantly associated with decreased cancer-specific survival (HR, 3.65; 95% CI, 1.04-12.84; P=0.0439). We concluded that intratumoral periostin expression was an independent prognostic factor for NSCLC.

Survival after initial lung metastasectomy for metastatic colorectal cancer in the modern chemotherapeutic era.

BACKGROUND: A clear survival benefit has been reported for lung metastasectomy for colorectal cancer, and several clinicopathological prognostic factors have been proposed in the past. However, clinical advances, such as chemotherapy and radiographic imaging, should have improved patient outcome and may have altered prognosticators. This study aimed to assess patient survival and determine prognostic factors for survival and recurrence in patients who underwent initial lung metastasectomy for colorectal cancer in the modern clinical era. METHODS: Clinicopathological data and outcomes of 59 patients who underwent curative initial lung metastasectomy for colorectal cancer from 2004 to 2012 at a single institution in Japan were retrospectively investigated. Survival was estimated using the Kaplan - Meier method, and Cox proportional hazards regression models were used to estimate the prognostic impacts of each variable in univariate and multivariate analysis. RESULTS: The 5-years overall and disease-free survival rates were 54.3 and 40.6%, respectively. A disease-free interval < 24 months after colorectal cancer resection (P = 0.004) and a serum carcinoembryonic antigen ≥ 5.0 ng/mL before initial lung metastasectomy (P = 0.015) were independent predictors for poor overall survival. Moreover, the disease-free interval after colorectal cancer resection < 24 months (P = 0.010) and a colorectal cancer with N2 stage disease (P = 0.018) were independently associated with poor disease-free survival. On the other hand, the number of lung metastasis was not identified as a poor prognostic factor for both overall and disease-free survival. CONCLUSIONS: Our findings demonstrated similar or slightly better overall survival, and substantially favorable disease-free survival as compared with past reports. Poor prognostic factors for overall survival appeared not to differ from those of past studies, although this modern series did not determine the number of lung metastasis as a poor prognostic factor, which should be investigated in future studies. Moreover, initial lung metastasectomy is not expected to be a curable treatment for patients with both a short disease-free survival after colorectal cancer resection and colorectal cancers with N2 stage disease.

Experimental validation of talc pleurodesis for carcinomatous pleuritis in an animal model.

OBJECTIVE: This study was performed to evaluate the change of pleural cavity by talc pleurodesis for carcinomatous pleuritis in an animal model. METHODS: Models of malignant pleuritis were produced by an intra-venous injection of lung adenocarcinoma cells to male BALB/c nude mice at 6 weeks of age. Two weeks after the injection, either talc or saline was injected into the left thoracic cavity and the mice were further observed for 4 weeks. Six weeks after the injection, they were killed and the occurrence of lung cancer, amount of pleural effusion, and histological change of the pleural cavity were examined and compared between the two groups with or without talc administration. RESULTS: Talc administration caused a significant reduction in pleural effusion with no increase of pleural adhesion. Talc administration resulted in marked pleural thickening compared to saline treatment. The vascular architecture and its area did not differ between the two groups. CONCLUSION: Talc pleurodesis to reduce pleural effusion is valid for carcinomatous pleuritis, potentially through an acceleration of pleural thickening.

Sorting nexin 2-mediated membrane trafficking of c-Met contributes to sensitivity of molecular-targeted drugs.

The sorting nexin (SNX) family is a diverse group of cytoplasmic and membrane-associated proteins that are involved in membrane-trafficking steps within the endocytotic network. SNX1 and SNX2 are components of the mammalian retromer complex and they also play critical roles in the membrane trafficking of growth factor receptors including epidermal growth factor receptor (EGFR) and c-Met. The human lung cancer cell lines, which harbor activating mutations in the kinase domain of EGFR gene, are sensitive to EGFR-targeted drugs gefitinib or erlotinib. However, a lung cancer cell line harboring gene amplification of c-Met is sensitive to the c-Met-targeted drug SU11274 but not to EGFR-targeted drugs. C-Met overexpression is identified as one of the bypass mechanisms for acquired resistance to EGFR-targeted drugs. Here we show that the siRNA-mediated knockdown of SNX2 decreases the cell-surface localization of c-Met, but not that of EGFR, resulting in lysosomal degradation of the c-Met protein. SNX2 specifically interacts with c-Met and treatment with lysosomal inhibitors almost completely annihilates downregulation of c-Met protein by SNX2 knockdown. Therefore, silencing of SNX2 markedly alters sensitivity to anticancer drugs targeted to c-Met (SU11274) and EGFR (gefitinib and erlotinib) through promotion of compensatory activation of the EGFR pathway in lung cancer cells. These findings suggest that development of drugs targeting SNX2 could be useful in overcoming drug resistance to EGFR-targeted drugs in lung cancer cells harboring c-Met gene amplification.

Neutrophil elastase activity in pulmonary venous blood during lung resection.

OBJECTIVES: Neutrophil elastase has been reported to play an important role in acute lung injury, which is a major cause of postoperative mortality after pulmonary resection. Neutrophil elastase released in the lungs reaches the peripheral circulation via the pulmonary veins. This study was performed to compare neutrophil elastase activity in pulmonary venous blood (collected during lobectomy) with that in the peripheral blood, and to determine the perioperative changes of neutrophil elastase activity. METHODS: In 34 patients undergoing lobectomy with mediastinal lymph node dissection, the leucocyte count, neutrophil count, neutrophil elastase activity and levels of tumour necrosis factor-α, interleukin-6 and interleukin-8 were measured in the pulmonary venous blood and peripheral arterial blood before and after surgery. Then, these parameters were compared between before and after surgery with peripheral and pulmonary blood. RESULTS: Neutrophil elastase activity was found to be significantly higher in pulmonary venous blood at the completion of surgery than at the start (during thoracotomy), while the neutrophil elastase activity of peripheral arterial blood showed no significant change between the start and completion of surgery. CONCLUSIONS: In conclusion, measurement of neutrophil elastase activity in pulmonary venous blood revealed changes associated with lobectomy.

Factors related to an early restoration of exercise capacity after major lung resection.

PURPOSE: We attempted to identify the factors related to an early restoration of the exercise capacity after lung resection. METHODS: Major lung resection was performed in 164 patients. Exercise testing and spirometry were performed before surgery, and 2 weeks and 1 month afterward. During exercise, the maximum oxygen uptake per minute per m(2) of body surface area (VO(2)max/m(2)) was measured. The percent change of VO(2)max/m(2) at 2 weeks and 1 month after surgery was calculated by setting the preoperative VO(2)max/m(2) value as 100%. Patients were then assigned to the early restoration group or late restoration group according to their VO(2)max/m(2) measured 2 weeks after surgery. Preoperative cardiopulmonary function, as well as various preoperative and intraoperative factors were compared between the two groups. RESULTS: At 2 weeks after surgery, the mean VO(2)max/m(2) was 80.9% compared with that before surgery, and was 88.1% at 1 month. A multivariate analysis showed that the surgical method used (thoracotomy and mediastinal lymph node dissection) had a significant effect on the postoperative restoration of the VO(2)max/m(2). CONCLUSION: An early restoration of exercise capacity after lung resection is possible in patients without mediastinal lymph node dissection and in those who have a small thoracotomy wound.

Selection of pulmonary resection procedures to reduce postoperative complications in 200 patients.

PURPOSE: We previously demonstrated in a pilot study that postoperative cardiopulmonary complications could be reduced by selecting pulmonary resection procedures based on the results of a combination of specific preoperative cardiopulmonary function tests. The present study reports a re-examination of the criteria for preoperative screening and prospectively assessed whether the selected surgical procedures were appropriate in 200 patients who underwent the planned extent of pulmonary resection. METHODS: In 200 patients requiring lung tumor resection, five preoperative parameters (forced expiratory volume in 1 s on the intact side, maximal oxygen uptake, ejection fraction, occluded pulmonary artery pressure, and occluded total pulmonary vascular resistance index) were used to assign each patient to one of five risk categories in order to select the optimal resection procedure. Thereafter, the postoperative course was investigated to determine the value of this selection method. RESULTS: Thoracotomy was performed in 195 of the 200 patients (97.5%). Two patients (1%) died; one patient succumbed to acute exacerbation of interstitial pneumonia and the other patient died from pulmonary embolism. Six patients (3.1%) developed major complications after surgery and 12 patients (6.2%) had mild complications, while 175 (89.7%) showed a good postoperative course. CONCLUSION: The use of five preoperative parameters to select the pulmonary resection procedure minimized postoperative death and major complications.

Giant liposarcoma occupying most of the hemi-thorax and resected in the supine position: report of a rare case.

Liposarcoma originating in the thoracic cavity is not common. It has been reported that neither chemotherapy nor radiotherapy is effective, and that surgical resection is the only therapeutic option. There have been several cases reported of a large liposarcoma compressing adjacent organs such as the lung and the heart. In such cases, careful management is required to prevent adverse cardiopulmonary events during resection. Here we report a rare case of a 52-year-old male who had a giant liposarcoma occupying the majority of the right thorax. The patient was placed in the supine position, and the tumor was resected through an anterior thoracotomy. Percutaneous cardiopulmonary support (PCPS) was prepared in case of need. However, we succeeded in resecting the huge tumor without use of PCPS. We were unable to completely resect the tumor because it originated from the posterior mediastinum and extended into the left thorax. The resected tumor weighed 3,500 g and was 28 cm in largest diameter. The postoperative course was uneventful, except for hypoxemia lasting a few days caused by re-expansion edema in the lung. The patient was discharged and is alive at five years to date.

Molecular diagnosis of activating EGFR mutations in non-small cell lung cancer using mutation-specific antibodies for immunohistochemical analysis.

PURPOSE: Therapeutic responses of non-small cell lung carcinoma (NSCLC) to epidermal growth factor receptor (EGFR)-targeted drugs, such as gefitinib and erlotinib, are closely associated with activating EGFR mutations. The most common mutations are delE746-A750 in exon 19 and L858R in exon 21, accounting for approximately 90% of all EGFR mutations. Recently, EGFR mutation-specific antibodies were developed and did well in immunohistochemical analysis, giving a sensitivity of approximately 90%. We have investigated whether this method detects activating EGFR mutations with sensitivity comparable with direct DNA sequencing, which is used to detect these mutations in NSCLC. EXPERIMENTAL DESIGN: We used antibodies specific for the E746-A750 deletion mutation in exon 19 and the L858R point mutation in exon 21 in Western blot analysis and immunohistochemistry to determine the presence of these mutations in NSCLC cell lines. We also examined these EGFR mutations in NSCLC tumor samples from 60 patients by immunohistochemically and direct DNA sequencing. RESULTS: We were able to identify EGFR mutations in NSCLC tumor samples immunohistochemically with a sensitivity of 79% using the anti-delE746-A750 antibody and 83% using the anti-L858R antibody. Additional DNA sequencing markedly improved the sensitivity obtained by immunohistochemistry. CONCLUSIONS: This simple and rapid assay for detecting EGFR mutations, even in the small bronchial biopsies obtained in stage IV NSCLC patients, will be useful for diagnosing responsiveness to EGFR-targeted drugs in patients with NSCLC. Combining this with DNA sequencing is recommended for the development of improved personalized EGFR-targeted therapeutics.

Nuclear Y-box binding protein-1, a predictive marker of prognosis, is correlated with expression of HER2/ErbB2 and HER3/ErbB3 in non-small cell lung cancer.

INTRODUCTION: Nuclear expression of Y-box binding protein-1 (YB-1) is closely associated not only with global drug resistance and expression of several growth factor receptors in various human malignancies but also with overall patient survival. METHODS: The effect of YB-1 knockdown on expression of epidermal growth factor receptor (EGFR) family proteins was examined by Western blot using human lung cancer cell lines. Immunohistochemistry was used to evaluate the expression of nuclear YB-1 and EGFR family proteins in patients with non-small cell lung cancer (NSCLC) (n = 104). RESULTS: In the five NSCLC cell lines, expressions of EGFR, human epidermal growth factor receptor 2 (HER2), HER3, and hepatocyte growth factor receptor (c-Met) in PC-9 cells; of HER2 and c-Met in EBC-1 cells; and of HER3 in QG56 cells were down-regulated by YB-1 knockdown. By immunohistochemical analysis, we observed that HER3 expression was significantly negatively correlated with nuclear YB-1 expression in squamous cell carcinoma (p = 0.038). HER2 expression was positively correlated with nuclear YB-1 expression in adenocarcinoma (p = 0.052). Nuclear expression of YB-1 correlated with overall survival of all patients (p = 0.028) and of patients with adenocarcinoma (p = 0.007). Furthermore, there was a significant difference in therapeutic efficacies of gefitinib between patients with nuclear YB-1 expression and those with non-nuclear YB-1 expression in patients with NSCLC (p = 0.004, n = 26) but not between those with high and those with low expression of EGFR, HER2, HER3, and c-Met. CONCLUSION: Nuclear YB-1 expression might be essential for the malignant phenotype in lung cancer patients and might be an important biomarker for the development of therapeutic strategy against NSCLC.

[A case of advanced gastric cancer with giant lymph node metastasis responding to S-1/CDDP neoadjuvant chemotherapy].

The patient was a 66-year-old man with advanced gastric cancer and bulky lymph node metastases. Since a radical resection appeared impossible, we tried neoadjuvant chemotherapy (NAC) with S-1/CDDP, expecting down staging of the tumor. S-1 (120 mg/body) was orally administered for 21 days and CDDP (40 mg/body) was administered by intravenous drip on day 8, 15 and 22. Partial response (PR) was obtained after 2 courses, and distal gastrectomy with D2 lymph node dissection was performed. The histological diagnosis revealed complete disappearance of cancer cells in stomach and a few regional lymph node metastasis (3/30). The patient was administered S-1 for one year after operation, and he is well without recurrence at one year and four months postoperatively. We considered the S-1 and CDDP in combination useful as preoperative chemotherapy for advanced gastric cancer.

Selection of pulmonary resection procedures to avoid postoperative complications.

PURPOSE: We previously found a potential predictive value in a retrospective analysis of spirometry and an expired gas analysis during the exercise. We sought to reduce postoperative cardiopulmonary complications by selecting lung tumor resection procedures based on a combination of specific preoperative cardiopulmonary function test results. METHODS: Out of the 53 patients requiring a lung tumor resection, five preoperative parameters (forced expiratory volume in 1 s for intact-side, maximal oxygen uptake, ejection fraction, occluded pulmonary artery pressure, and occluded total pulmonary vascular resistant index) were used to assign patients to one of five risk categories in order to select the optimal pulmonary resection procedure. The patients were later grouped according to their postoperative course to test the value of this procedure selection method. RESULTS: No patient died or developed severe complications after surgery. Five patients had mild complications, while 46 had a good postoperative course; the 13 deaths, in the cancer cases, included 11 from primary or metastatic cancer and 2 from other causes. The overall five-year survival was 61.4%. CONCLUSION: This method for determining a pulmonary resection procedure avoided postoperative deaths and severe cardiopulmonary complications, while achieving a good outcome.