The association of visceral pleural invasion with skip N2 metastasis on clinical stage IA NSCLC.

BACKGROUND: Lung lymphatic drainage occurs mainly through a peribronchial path, but it is hypothesized that visceral pleural invasion could alter this path. This study aims to investigate the association between visceral pleural invasion, node upstaging, and N2 skip metastasis and the impact on survival in a population of patients with non-small cell lung cancer of 3 cm or smaller. METHODS: We retrospectively queried our institutional database of lung cancer resection for all patients with clinical stage IA NSCLC between June 2009 and June 2022. We collected baseline characteristics and clinical and pathological staging data. Patients were classified into two groups: The non-VPI group with negative visceral pleural invasion and the VPI group with positive. The primary results analyzed were the occurrence of nodal upstaging, skip N2 metastasis and recurrence. RESULTS: There were 320 patients analyzed. 61.3 % were women; the median age was 65.4 years. The pleural invasion occurred in 44 patients (13.7 %). VPI group had larger nodules (2.3 vs. 1.7 cm; p < 0.0001), higher 18F-FDG uptake (7.4 vs. 3.4; p < 0.0001), and lymph-vascular invasion (35.7 % vs. 13.5 %, p = 0.001). Also, the VPI group had more nodal disease (25.6 % vs. 8.7 %; p = 0.001) and skip N2 metastasis (9.3 % vs. 1.8 %; p = 0.006). VPI was a statistically independent factor for skip N2 metastasis. Recurrence occurred in 17.2 % of the population. 5-year disease-free and overall survival were worse in the VPI group. CONCLUSIONS: The visceral pleural invasion was an independent factor associated with N2 skip metastasis and had worse disease-free and overall survival.

The association of visceral pleural invasion with skip N2 metastasis on clinical stage IA NSCLC

Abstract Background Lung lymphatic drainage occurs mainly through a peribronchial path, but it is hypothesized that visceral pleural invasion could alter this path. This study aims to investigate the association between visceral pleural invasion, node upstaging, and N2 skip metastasis and the impact on survival in a population of patients with non-small cell lung cancer of 3 cm or smaller. Methods We retrospectively queried our institutional database of lung cancer resection for all patients with clinical stage IA NSCLC between June 2009 and June 2022. We collected baseline characteristics and clinical and pathological staging data. Patients were classified into two groups: The non-VPI group with negative visceral pleural invasion and the VPI group with positive. The primary results analyzed were the occurrence of nodal upstaging, skip N2 metastasis and recurrence. Results There were 320 patients analyzed. 61.3 % were women; the median age was 65.4 years. The pleural invasion occurred in 44 patients (13.7 %). VPI group had larger nodules (2.3 vs. 1.7 cm; p < 0.0001), higher 18F-FDG uptake (7.4 vs. 3.4; p < 0.0001), and lymph-vascular invasion (35.7 % vs. 13.5 %, p = 0.001). Also, the VPI group had more nodal disease (25.6 % vs. 8.7 %; p = 0.001) and skip N2 metastasis (9.3 % vs. 1.8 %; p = 0.006). VPI was a statistically independent factor for skip N2 metastasis. Recurrence occurred in 17.2 % of the population. 5-year disease-free and overall survival were worse in the VPI group. Conclusions The visceral pleural invasion was an independent factor associated with N2 skip metastasis and had worse disease-free and overall survival.

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.

Peripheral location of lung cancer is associated with higher local disease recurrence.

OBJECTIVES: Our goal was to evaluate the association between the distance of the tumour to the visceral pleura and the rate of local recurrence in patients surgically treated for stage pI lung cancer. METHODS: We conducted a single-centre retrospective review of 578 consecutive patients with clinical stage IA lung cancer who underwent a lobectomy or segmentectomy from January 2010 to December 2019. We excluded 107 patients with positive margins, previous lung cancer, neoadjuvant treatment and pathological stage II or higher status or for whom preoperative computed tomography (CT) scans were not available at the time of the study. The distance between the tumour and the closest visceral pleura area (fissure/mediastinum/lateral) was assessed by 2 independent investigators who used preoperative CT scans and multiplanar 3-dimensional reconstructions. An area under the receiver operating characteristic curve analysis was performed to determine the best threshold for the tumour/pleura distance. Then multivariable survival analyses were used to assess the relationship between local recurrence and this threshold in relation to other variables. RESULTS: Local recurrence occurred in 27/471 patients (5.8%). A cut-off value of 5 mm between the tumour and the pleura was determined statistically. In the multivariable analysis, the local recurrence rate was significantly higher in patients with a tumour-to-pleura distance ≤5 mm compared to patients with a tumour-to-pleura distance >5 mm (8.5% vs 2.7%, hazard ratio 3.36, 95% confidence interval: 1.31-8.59, P = 0.012). Subgroup analyses of patients with pIA and tumour size ≤2 cm identified local recurrences in 4/78 patients treated with segmentectomy (5.1%), with a significantly higher occurrence with tumour-to-pleura distances ≤5 mm (11.4% vs 0%, P = 0.037), and in 16/292 patients treated with lobectomy (5.5%) without significant higher occurrence in tumour-to-pleura distances of ≤5 mm (7.7% vs 3.4%, P = 0.13). CONCLUSIONS: The peripheral location of a lung tumour is associated with a higher rate of local recurrence and should be taken into account during preoperative planning when considering segmental versus lobar resection.

Nephronectin is required to maintain right lung lobar separation during embryonic development.

Nephronectin (NPNT) is a basement membrane (BM) protein and high-affinity ligand of integrin α8ß1 that is required for kidney morphogenesis in mice. In the lung, NPNT also localizes to BMs, but its potential role in pulmonary development has not been investigated. Mice with a floxed Npnt allele were used to generate global knockouts (KOs). Staged embryos were obtained by timed matings of heterozygotes and lungs were isolated for analysis. Although primary and secondary lung bud formation was normal in KO embryos, fusion of right lung lobes, primarily the medial and caudal, was first detected at E13.5 and persisted into adulthood. The lung parenchyma of KO mice was indistinguishable from wild-type (WT) and lobe fusion did not alter respiratory mechanics in adult KO mice. Interrogation of an existing single-cell RNA-seq atlas of embryonic and adult mouse lungs identified Npnt transcripts in mesothelial cells at E12.5 and into the early postnatal period, but not in adult lungs. KO embryonic lungs exhibited increased expression of laminin α5 and deposition of collagen IV in the mesothelial BM, accompanied by abnormalities in collagen fibrils in the adjacent stroma. Cranial and accessory lobes extracted from KO embryonic lungs fused ex vivo when cultured in juxtaposition, with the area of fusion showing loss of the mesothelial marker Wilms tumor 1. Because a similar pattern of lobe fusion was previously observed in integrin α8 KO embryos, our results suggest that NPNT signaling through integrin α8, likely in the visceral pleura, maintains right lung lobe separation during embryogenesis.

Abrupt Bulla Formation by Visceral Pleural Detachment after Pulmonary Lobectomy: A Case Report.

Pulmonary bullae usually grow slowly and have thin walls. However, we have observed 2 cases of abrupt bulla formation immediately after lobectomy and during surgery. The pathologic findings of what can be called visceral pleural detachment are quite distinctive: these bullae had a broad base connected to the lung, and their walls were thick, including the full extent of visceral pleural and peripheral alveolar tissues, which suggests that the visceral pleura were detached from the distal alveoli. High transpleural pressure might be the key factor in the pathogenesis of this type of bulla, unlike previously known types of bullous lung disease.

Role of visceral pleural invasion and tumor sizing at CT of resected NSCLC in clinical-radiological and pathological T agreement.

OBJECTIVE: To describe in non-small cell lung cancer (NSCLC) the impact of visceral pleural invasion (VPI) and of tumor sizing assessed at computed tomography (CT) on the agreement between clinical-radiological and pathological T staging and its prognostic value. METHODS: Patients affected by NSCLC treated by surgery in the period from January 2017 to September 2020 were retrospectively evaluated. Exclusion criteria were: (1) baseline CT not performed in our hospital; (2) failure of software segmentation at CT of the primary lesion. Clinical-radiological T (cT) was assessed at baseline CT, evaluating in particular T size by semi-automatic tool and VPI (cVPI) visually. Pathological T (pT) and VPI (pVPI) were recorded by pathological report and obtained after formalin-fixation and eventual elastic stain on surgical specimen. The agreement between cT and pT was evaluated by calculating the weighted kappa by Cohen (κw); the association between progression free survival (PFS) with both cT and pT was assessed by the Cox regression analysis. RESULTS: The study included 84 NSCLC in 82 patients (median age 71 years, IQR 63-76 years; females 22/82, 27%). The agreement between cT and pT was poor (κw 0.302, 95%CI 0.158-0.447). The main causes of disagreement were CT oversizing (21%) and false positive cVPI (29%). A significant association was found between PFS and pT2-T3 (HR 2.75, 95%CI 1.21-6.25, p=0.015) but not with cT2-T3 (not retained in the model). CONCLUSIONS: False positive cVPI and oversizing at CT are causes of disagreement between cT and pT in around one-third of resected NSCLC. PFS was significantly associated with pT but not with cT.

A case of a thoracic mass negative on thoracentesis diagnosed by cryobiopsy from the visceral pleura.

Thoracoscopy under local anaesthesia is recommended for malignant tumours with negative pleural effusion cytology. Cryobiopsy from the visceral pleura by thoracoscopy under local anaesthesia can provide more diagnostic options for patients with thoracentesis-negative malignant effusions. Here we present the first case in which this technique was used. The patient had a pleural metastasis that could not be diagnosed even with rapid cytology of the parietal pleura biopsy. Indications, technical pitfalls, and safety tips are discussed.

Novel Biomaterial for Artery Patch in Swine Model With High-Fat Diet.

OBJECTIVE: We evaluated swine and bovine pulmonary visceral pleura (PVP) in artery patch-angioplasty in swine model of high-fat diet. BACKGROUND: Arterial patch-angioplasty is frequently used for repair or reconstruction of arteries. An autologous patch is often limited by the number and dimension of donor tissue and can result in donor complications. Furthermore, mechanical mismatch is a cause of poor performance of vascular reconstruction. Here, we introduce a readily available patch biomaterial with similar compliance as native arteries. METHODS: The PVP was peeled from swine and bovine lungs by hydro-dissection. The swine and bovine PVPs were crosslinked with glutaraldehyde and then sterilized. The swine PVP (sPVP) patches were implanted in the carotid and femoral arteries of six Yorkshire pigs that were fed a regular diet and euthanized at 2 and 4 months postoperative. The bovine PVP (bPVP) patches were implanted in the carotid artery of six Yucatan pigs that were fed a high-fat diet and euthanized at 4 months postoperative. Patency was evaluated by ultrasound and angiography. Neo-endothelium and media were evaluated by histologic examination. RESULTS: All arteries in patch-angioplasties remained patent with no adhesions, inflammation, or aneurysms. Biomarkers of endothelial cells (e.g., Factor VIII and eNOS) were detected in the neo-endothelial cells. We observed endothelial cell-cell junctions in the confluent neo-endothelium in the PVP patches. Neo-media composed of vascular smooth muscle developed similar as native arteries. In the hypercholesterolemic model, we observed the accumulation of cholesterol in both arterial tissues and in the neo-vascular tissues in the PVP patches. Protein expressions of lipid transport and metabolism (e.g., APOE-1, ABCA, and PACK9) were also observed in both arterial and neo-vascular tissues. CONCLUSION: The PVP patch-angioplasty overcomes the pitfalls of compliance mismatch of synthetic patches and has a non-thrombogenic surface. The proliferation of vascular cells assembled to generate the neo-endothelium and media in the patch-angioplasties to support long-term patency. The neo-vascular tissue in PVP patch-angioplasty also developed similar cellular functions for lipid transport and metabolism compared with native arteries in hypercholesterolemia.

Lymphatic drainage of lung cancer follows an intersegmental pathway within the visceral pleura.

OBJECTIVES: Lung cancer tumors are known to be highly lymphophilic. There are two different pattern of lymphatic drainage of the lung: one peribronchial lymphatic pathway, and another one within the visceral pleura which appears to be more intersegmental than the peribronchial pathway. We aimed to assess the prevalence of an intersegmental pathway in the lymphatic drainage of lung tumors within the visceral pleura and determine potential influential factors. METHODS: In this prospective study, we included all patients for whom a major pulmonary resection (lobar) was indicated and performed for suspected or proven lung cancer. An immediate ex-vivo evaluation of the surgical specimen after resection was conducted by trans-pleural injection of blue dye within the tumor. The pathways followed by the lymphatic vessels under the visceral pleura were assessed to define the occurrence of an intersegmental pathway, which was defined by the presence of blue dye within the lymphatic vessel crossing to a neighboring pulmonary segment, distinct from the tumorous segment. RESULTS: Fifty-three patients met the inclusion criteria and were assessed over a three-year period. Lymphatic drainage within the visceral pleura followed an intersegmental pathway in 35 of 53 patients (66 %). When the lymphatic drainage of the tumor was intersegmental, it drained in a single other segment in 21/35 cases and two or more in 14/35 cases. Logistic regression with multivariate analysis showed a peripheral location of the tumor to be a risk factor for the intersegmental pathway of visceral pleura lymphatic drainage (OR = 0.87 [079-0.95], p = 0.003). CONCLUSION: These results confirm that lymphatic drainage of lung cancer in the visceral pleura appears to largely follow an intersegmental pathway, especially when the tumor is peripheral, close to the visceral pleura.

Comparison of Hydroxyethyl starch 130/0.4 (6%) with commonly used agents in an experimental Pleurodesis model.

BACKGROUND: Hydroxyethyl Starch (HES) 130/0.4 (6%) is a commonly used intravascular volume expander with anti-inflammatory and antioxidant properties. In this study, we aimed to compare the histopathologic activity of HES 130/0.4 (6%) with various widely-used agents in pleurodesis. METHODS: Forty male Wistar-Albino rats were divided into five groups: controls, povidone-iodine recipients (PI group), sterile talcum recipients (Talcum group), autologous blood recipients (AB group) and HES 130/0.4 (6%) recipients (HES group). Thirty days after application of agents, pleural and lung tissues were resected. Evaluation was performed via macroscopic scoring (adhesion) and specimens were stained with H&E for microscopic examination (inflammation and fibrosis). RESULTS: HES recipients had significantly higher adhesion compared to controls (lower grade 0, higher grade 1 frequency vs. controls), they were found to have significantly lower frequency of grade 2 adhesion (vs. PI, Talc and AB) and grade 3 adhesion (vs. AB), indicating that the adhesion-generating properties of HES were only superior to the control group. HES recipients had significantly higher inflammatory grades compared to controls (lower grade 0, higher grade 1 frequency), while they had lower grades compared to the PI, Talc and AB groups. Although the PI, Talc and AB groups were statistically similar in most comparisons, we observed a trend towards higher success with the use of Talc and especially AB. CONCLUSION: Our results do not support a role for HES in pleurodesis. We believe that the autologous blood method remains as an effective and successful procedure without side effects.

Visceral pleural biopsy under medical thoracoscopy for the diagnosis of lung adenocarcinoma.

Medical thoracoscopy is a minimally invasive single-port endoscopic technique that provides direct visualization of the pleural surface and allows for diagnostic procedures. The diagnostic yield of medical thoracoscopy is high and is generally based on parietal pleural biopsy findings. Pleural biopsies are valuable for a diagnosis. However, visceral pleural biopsies are uncommon because of the risk of prolonged air leak. In this study, we report a rare case of the successful diagnosis of lung adenocarcinoma, based on the findings of visceral pleural biopsy under medical thoracoscopy. To avoid lung injury and pneumothorax, we focused on maintaining the thoracoscope and biopsy forceps in a straight angle as much as possible. While looking straight ahead at the visceral pleural nodule as closely as possible, biopsy samples were carefully obtained while confirming that the normal lung was not held. With careful consideration, visceral pleural biopsies may expand the diagnostic capability of medical thoracoscopy.

Homologous and heterologous assessment of a novel biomaterial for venous patch.

OBJECTIVE: This study evaluated swine and bovine pulmonary visceral pleura (PVP) as a vascular patch. Venous patches are frequently used in surgery for repair or reconstruction of veins. Autologous patches are often limited by the number and dimension of donor tissue and can result in donor complications. Bovine pericardium is the most common heterologous patch used by vascular surgeons. Researchers, however, are continually seeking to improve heterologous and synthetic patches for improved outcome. METHODS: The PVP was peeled from swine and bovine lungs and cross-linked with glutaraldehyde. After sterilization and rinsing, the PVP patches were implanted in the jugular vein (10 × 35 mm) of pigs and dogs. Patency was evaluated by ultrasound, and animals were euthanized at 2 and 4 months. Neoendothelium and neomedia were evaluated by histologic analysis. RESULTS: The jugular vein patched by PVP in pigs and dogs remained patent at 2 and 4 months with no adhesions, inflammation, or aneurysm in the patches. The biomarkers of endothelial cells-factor VIII, platelet/endothelial cell adhesion molecule 1, and endothelial nitric oxide synthase-were detected in the neoendothelial cells. The expression of vascular smooth muscle cell (VSMC) α-actin was robust in the neomedia at 2 and 4 months. Neomedia composed of VSMCs developed to nearly double the thickness of adjacent jugular vein. The circumferential orientation of VSMCs in neomedia further increased in the 4-month group. CONCLUSIONS: The cross-linked swine and bovine PVP patch has a nonthrombogenic surface that maintains patency. The PVP patch may overcome the pitfall of compliance mismatch of synthetic patches. The proliferation of vascular cells assembled in the neoendothelium and neomedia in the patches may support long-term patency.

Pathological evaluation of the visceral pleura in the radical pleurectomy/decortication for malignant pleural mesothelioma patients.

BACKGROUND: Radical pleurectomy/decortication (P/D) is applied as a surgical treatment of resectable malignant pleural mesothelioma (MPM). Although P/D removed visceral pleura, dissection plain was not histologically explored previously. We examined a pathological evaluation of surgically removed visceral pleura in P/D. METHODS: Twenty-five patients with MPM who underwent P/D at the Tokyo Medical and Dental University Hospital between April 2010 and April 2018 were studied. The 25 cases included 20 with epithelioid tumors, 4 with a biphasic tumor and 1 with desmoplastic tumors. Nine, 1, 11 and 4 patients had mesotheliomas of stages I, II, III and IV, respectively. We analyzed the site of the visceral pleural lesions using the HE & Elastica van Gieson (EVG) staining. The tumor involvement of the pleura and the surgical dissection plane were defined using the depth criteria, D0-3. We added survival analyses according to the depth criteria. RESULTS: Ninety-nine lesions in total 45 lobes: 20 upper right, 14 middle, 20 lower, 22 upper left, and 23 lower were examined. Based on the depth D 0-3 criteria, there were 21 type D0, 18 type D1, 22 type D2 and 38 type D3 lesions. The growth of tumor cells in the pleura was partially diffuse or nodular in all cases. While 38 lesions which invaded the lung parenchyma were excised, another 61 lesions that reached within the pleura were dissected from lung parenchyma. Type D2&3 showed poor survivals than type D0&1. CONCLUSIONS: The lung parenchyma was always the dissection plane in P/D, regardless of tumor involvement in the visceral pleura. The depth criteria would help us in classifying pleural invasion histologically and possibly predicting the prognosis.

CT diagnosis of pleural and stromal invasion in malignant subpleural pure ground-glass nodules: an exploratory study.

OBJECTIVES: To assess the risk of visceral pleural invasion (VPI) and improve the diagnosis of invasive adenocarcinoma (IA) in pure ground-glass nodules (pGGNs) in contact with pleura, through a comprehensive analysis of the thin-section CT features of subpleural malignant pGGNs. METHODS: CT findings and clinical information of 115 consecutive patients in our hospital between January 2012 and December 2015 who met the following criteria were retrospectively studied: (a) thin-section CT within 1 month before surgery proved pGGN in contact with pleura, and (b) the pGGN was confirmed as malignancy by surgery. Univariate analysis and a multivariate logistic regression analysis were conducted to identify the independent risk factors of IA and VPI. RESULTS: No pleural invasion was observed microscopically in any of the pGGNs. Univariate analysis indicated that tumour shape (p = 0.004), relative density (p = 0.038) and the existence of pleural retraction (p < 0.001) were significantly different between the invasive group and pre- or minimally invasive group. Multivariate logistic regression analysis revealed that pleural retraction (OR, 5.663; p < 0.001), lobulated tumour shape (OR, 4.812; p = 0.016) and tumour relative density greater than 1.60 (OR, 4.449; p = 0.001) were independent risk factors of IA. CONCLUSIONS: Pulmonary adenocarcinoma manifesting as pGGN generally does not invade the pleura. A comprehensive consideration of tumour shape, relative density and tumour-pleural relationship can independently predict IA. KEY POINTS: • This study showed that pGGN-like adenocarcinoma generally does not invade the pleura. • This study suggested that persistent pGGN with pleural retraction, lobulated shape and high relative density (> 1.60) may very likely be invasive adenocarcinoma. • Using "relative density" can reduce confounding of contrast agent and respiratory status in analysis of CT images.

In vivo self-assembly of small diameter pulmonary visceral pleura artery graft.

BACKGROUND: There is a significant clinical need for small vascular grafts <1 mm in diameter. MATERIALS AND METHODS: The structure and composition of swine pulmonary visceral pleura (PVP) were investigated. Two processes, glutaraldehyde (GA) crosslink and decellularization (dc) plus GA crosslink, were used to inhibit the immune response. The thrombosis-resistance of the GA-crosslinked PVP (GA-PVP) was determined with in vitro and in vivo studies. Small vessel grafts with 0.7 diameter mm were constructed using the GA-PVP and surgically interposed in the femoral artery of rats for up to 24 weeks. Blood flow in the GA-PVP grafts were measured and ex vivo vascular reactivity of the prostheses were evaluated along with immuno-histological analysis. RESULTS: The GA-PVP mesothelium contains abundant glycocalyx-like substance and a smooth surface. The mechanical properties of the GA-PVP were similar to the femoral artery of rat in the range of physiological pressures. The in vitro and in vivo studies confirmed poor platelet adhesion on the GA-PVP mesothelial surface in comparison with dc processed PVP (dc-PVP). Patency of the GA-PVP prostheses in femoral arteries of rats was 86% in the 24 weeks postoperative period while patency of dc-PVP in femoral arteries of rats was 33% at 1 week postoperative period. Blood flow in the GA-PVP prostheses were not statistically different than the contralateral femoral artery. Biomarkers of neo-endothelial cells, neo-media smooth muscle cells, and extracellular matrices were observed in the GA-PVP prostheses. The significant agonists-induced vasoconstriction and endothelium-dependent vasodilation were apparent at 12 weeks and further amplified in the 24 weeks postoperative, which suggests self-assembly of functional neo-endothelium and neo-media. CONCLUSIONS: The high patency and functionality of the small grafts suggest that the GA-PVP is a promising prosthetic biomaterial for vascular reconstructions. STATEMENT OF SIGNIFICANCE: Small artery graft (diameter <1 mm) in the peripheral circulation that functionally arterializes has not been possible primarily due to thrombosis. Our findings indicate that lung visceral pleura may address thrombogenicity as the major pitfall in small diameter grafts. Here, grafts of 0.7 mm diameter were constructed from swine pulmonary visceral pleura (PVP) and implanted into femoral artery position of rats up to 24 weeks. The total patency of grafts in femoral arteries of rats was 86% in the 24-week period. The neo-endothelial and -medial layers were assembled in the grafts as evidenced by robust biomarkers of endothelial cells, smooth muscle cells, and extracellular matrices observed in the grafts. Agonists-induced vasoconstriction and endothelium-dependent vasodilation were apparent at 12 weeks and were amplified at 24 weeks. The high patency of the small grafts suggests that the PVP is a promising prosthetic biomaterial for vascular reconstructions.

Proposal on incorporating lymphovascular invasion as a T-descriptor for stage I lung cancer.

BACKGROUND: Lymphovascular invasion (LVI) and Visceral Pleural Invasion (VPI) have been reported to be risk factors for stage I Non-Small Cell Lung Cancer (NSCLC). However, only VPI was incorporated into the current 8th Tumor-Node-Metastasis (TNM) classification. This study aimed to explore the prognostic effect of LVI and VPI on TNM staging in pathological stage I NSCLC. METHOD: We retrospectively reviewed 2633 consecutive p-stage I NSCLC patients in the Shanghai Chest Hospital (2008-2012). By using the Kaplan-Meier method and Cox proportional hazard regression model, we identified the correlations between LVI, VPI, and clinical outcomes in p-stage 1 NSCLC. RESULTS: Of all 2633 p-stage I NSCLC patients, 222 were pathologically diagnosed with LVI and 836 pathologically with VPI. The 5-year recurrence free survival (RFS) and overall survival (OS) rates of patients with LVI was significantly worse compared to those without LVI (61.2% vs 82.0%, p < 0.001; 73.3% vs 88.1%, p < 0.001). The same results emerged for patients with VPI (70.1% vs 85.9%, p < 0.001; 82.3% vs 90.0%, p < 0.001). Using the univariable and multivariable analysis, we found that when tumor diameter was 3 cm or smaller, LVI (RFS: hazard ratio [HR], 2.54; 95% confidence interval [CI], 1.86-3.50; p < .001; OS: HR, 2.53; 95% CI, 1.72-3.71; p < .001) and VPI (RFS: HR, 2.14; 95% CI, 1.71-2.67; p < .001; OS: HR, 1.56; 95% CI, 1.12-2.04; p = 0.01) were significant prognostic factors for RFS and OS. When tumor size was between 3-4 cm, LVI (HR, 1.84; 95% CI, 1.03-3.29; p = 0.039) and VPI (HR, 2.56; 95% CI, 1.61-4.07; p < .001) were associated with inferior OS. CONCLUSIONS: The presence of LVI significantly affected OS and RFS in stage I NSCLC patients. Our results suggested that it might be better to incorporate LVI as a T descriptor as VPI in the further TNM classification.

Adjuvant chemotherapy may improve prognosis after resection of stage I lung cancer with lymphovascular invasion.

OBJECTIVES: This study explored the prognostic significance and adjuvant chemotherapy benefits in resected patients with stage I non-small cell lung cancer with lymphovascular invasion. METHODS: A total of 2633 patients who received complete resection with pathologic stage I non-small cell lung cancer in the Shanghai Chest Hospital (2008-2012) were enrolled in the study, of whom 222 were diagnosed with lymphovascular invasion. By using the Kaplan-Meier method and Cox proportional hazard regression model, we explored the impact of lymphovascular invasion on prognosis and determined if the use of adjuvant chemotherapy is associated with improved outcomes in patients with lymphovascular invasion. A propensity score-matched analysis was implemented to reduce the selection bias. RESULTS: Patients with lymphovascular invasion had an unfavorable overall survival and recurrence-free survival in stage I non-small cell lung cancer. Multivariate Cox analysis indicated that lymphovascular invasion was an independent poor prognostic factor for recurrence-free survival (hazard ratio [HR], 2.06; 95% confidence interval [CI], 1.58-2.71; P < .001) and overall survival (HR, 2.04; 95% CI, 1.45-2.87; P < .001) in patients with stage I. After using propensity score-matched pairs, analysis of 65 pairs of patients with lymphovascular invasion indicated a beneficial recurrence-free survival (HR, 0.33; 95% CI, 0.16-0.67; P = .002) and overall survival (HR, 0.30; 95% CI, 0.12-0.74; P = .009) from adjuvant chemotherapy. CONCLUSIONS: Lymphovascular invasion was correlated with poor prognosis in patients with stage I non-small cell lung cancer. For such patients, adjuvant chemotherapy was associated with improved survival. Our study suggests that adjuvant chemotherapy might be an appropriate option for patients with stage I non-small cell lung cancer with lymphovascular invasion.

Lymphatic drainage of lung segments in the visceral pleura: a cadaveric study.

PURPOSE: Although peribronchial lymphatic drainage of the lung has been well characterized, lymphatic drainage in the visceral pleura is less well understood. The objective of the present study was to evaluate the lymphatic drainage of lung segments in the visceral pleura. METHODS: Adult, European cadavers were examined. Cadavers with a history of pleural or pulmonary disease were excluded. The cadavers had been refrigerated but not embalmed. The lungs were surgically removed and re-warmed. Blue dye was injected into the subpleural area and into the first draining visceral pleural lymphatic vessel of each lung segment. RESULTS: Twenty-one cadavers (7 males and 14 females; mean age 80.9 years) were dissected an average of 9.8 day postmortem. A total of 380 dye injections (in 95 lobes) were performed. Lymphatic drainage of the visceral pleura followed a segmental pathway in 44.2% of the injections (n = 168) and an intersegmental pathway in 55.8% (n = 212). Drainage was found to be both intersegmental and interlobar in 2.6% of the injections (n = 10). Lymphatic drainage in the visceral pleura followed an intersegmental pathway in 22.8% (n = 13) of right upper lobe injections, 57.9% (n = 22) of right middle lobe injections, 83.3% (n = 75) of right lower lobe injections, 21% (n = 21) of left upper lobe injections, and 85.3% (n = 81) of left lower lobe injections. CONCLUSION: In the lung, lymphatic drainage in the visceral pleura appears to be more intersegmental than the peribronchial pathway is-especially in the lower lobes. The involvement of intersegmental lymphatic drainage in the visceral pleura should now be evaluated during pulmonary resections (and especially sub-lobar resections) for lung cancer.

Predictive CT Features of Visceral Pleural Invasion by T1-Sized Peripheral Pulmonary Adenocarcinomas Manifesting as Subsolid Nodules.

OBJECTIVE: The objective of our study was to determine whether visceral pleural invasion (VPI) of T1-sized peripheral pulmonary adenocarcinomas manifesting as subsolid nodules (SSNs) abutting the pleural surface or associated with pleural tags can be predicted. MATERIALS AND METHODS: Our study population consisted of 188 T1-sized peripheral pulmonary adenocarcinomas that appeared as SSNs (24 pure ground-glass nodules [GGNs] and 164 part-solid nodules) and underwent surgical resection between January 2007 and December 2013. Logistic regression analysis was performed to identify significant factors in predicting VPI. RESULTS: VPI occurred in 36 of 188 adenocarcinomas (19.1%). There were no cases of VPI in patients with pure GGNs. In part-solid nodules, there were significant differences regarding the presence of pleural contact, presence of pleural thickening, presence of solid portion abutting the pleura, nodule size, solid portion size, solid proportion, interface length, and length of the solid portion contacting the pleura (p < 0.05). Multivariate analysis revealed pleural contact (p < 0.001), pleural thickening (p = 0.003), solid proportion greater than 50% (p = 0.002), and nodule size greater than 20 mm (p = 0.015) as significant independent predictive features for VPI with adjusted odds ratios of 8.300, 3.966, 4.636, and 2.993, respectively. CONCLUSION: In part-solid nodules, the CT features of pleural contact, pleural thickening, solid proportion greater than 50%, and nodule size greater than 20 mm were shown to be significant indicators of VPI by T1-sized peripheral adenocarcinomas.