Diagnostic Utility of Virtual Bronchoscopic Navigation Assisted Endobronchial Ultrasonography with Guide Sheath for Peripheral Pulmonary Lesions

Background and objective Virtual bronchoscopic navigation (VBN) assisted endobronchial ultrasonography with guide sheath (EBUS-GS) has reduced the difficulty and even avoiding radiation exposure during performing transbronchus lung biopsy (TBLB). To evaluate the feasibility and safety of virtual bronchoscopic navigation assisted endobronchial ultrasonography with guide sheath for peripheral pulmonary lesions. Methods We performed a retrospective analysis of the patients with PPLs who received VBN assisted EBUS-GS-TBLB in Peking University Cancer Hospital from January 2016 to December 2017. Their clinicopathologic data and complications were assessed. Results A total of 121 patients were enrolled in the study. The patients included 65 men and 56 women, with a mean age of (58.8±10.3) years. A total of 121 PPLs were examined, and 108 lesions of which could be detected by EBUS. The overall diagnostic yield of EBUS-GS was 73.5%. The diagnostic yield of malignancy was 82.5%. The combination of transbronchial lung biopsy, brush smear and bronchoalveolar lavage fluid provided the greatest diagnostic yield (χ2=6.084, P=0.014). Factors that significantly affected and predicted diagnostic success were EBUS probe within the lesions (χ2=20.372, P=0.000) and PPLs located in the central two-thirds of the lung (χ2=10.810, P=0.001). 1 patient (0.8%) suffered from intraoperative bleeding which could be managed under endoscopy. Conclusion VBN assisted EBUS-GS-TBLB for PPLs was an effective and safe procedure

Survival Analysis of 121 Stage N2-IIIa Non-small Cell Lung Cancer Patients Treated with Surgery

Background and objective It has still been controversial to treat N2-IIIa non-small cell lung cancer (NSCLC) patients by surgery or non-surgery. We retrospectively analysed the survival of 121 stage N2-IIIa NSCLC patients treated with surgery and explored their postoperatively long-term prognostic factors. Methods All of 1,290 patients in Beijing Cancer Hospital underwent resection by single-surgeon-team, among which 121 cases with stage N2-IIIa were enrolled in the study. We retrospectively analysed the impact of gender, age, smoking, perioperative chemotherapy, incision, histological type, vascular tumor emboli, pTstage and tumor size on survival of stage N2-IIIa patients, and compared the survival between patients with single-and multi-station N2 metastasis, and between intraoperatively or postoperatively pathological N2 (IIIa1/a2) and preoperative N2 (IIIa3/a4). Univariate analysis was conducted by Kaplan-Meier curve, and significance test was performed by Log-rank test and Cox regression factor analysis was applicated for multivariate analysis. Results The 5-yr of all the 121 cases was 43.6%, with a median survival time being 50.3 mo. Univariate analysis showed the 5-year survival rate in patients with single- and multi- station N2 metastasis were 58.3% and 25.5%, respectively (P=0.001), 5-year survival rate in patients with stage IIIa1/a2 and stag IIIa3/a4 were 52.7% and 38.4%, respectively (P=0.020). Multivariate analysis demonstrated that only single station N2 (HR=0.326, 95%CI: 0.186-0.572, P<0.001) and IIIa1/a2 (HR=0.494, 95%CI: 0.259-0.941, P=0.032) were independent prognostic factors for stage N2-IIIa lung cancer patients. Conclusion The prognosis of stage N2-IIIa NSCLC patients with single-station N2 metastasis were better than those with multi-station N2 metastasis. Besides, IIIa1/a2 patients had a better survival compared with stage IIIa3/a4 patients. A multi-disciplinary comprehensive treatment based on surgery may allow patients with high selective stage N2-IIIa NSCLC to obtain a comparatively satisfying long-term survival

The Current Immunohistochemistry Markers in the Resected Tissues of Non-small Cell Lung Cancer Could Not Predict Prognosis

Background and objective It has been drawn much attention to identify the molecular markers by immunohistochemistry (IHC) for evaluating the prognosis of non-small cell lung cancer (NSCLC) following resection. The aim of this study is to retrospectively associate ever tested IHC markers and prognosis of NSCLC after resection. Methods A total of 722 NSCLC patients underwent surgery by single surgeon team from 2008 to 2013. Twelve molecular markers had been examined by IHC and the staining signals was re-scored with unified standard. Survival analysis by univariate and multivariate was carried out to assess the significance of these markers in prognosis of NSCLC in our prospective database with strict follow-up. Results The following twelve IHC markers had been tested between 2008 and 2013, including platelet-derived growth factor receptor (PDGFR)(n=124), excision repair cross complementing 1 (ERCC1)(n=124), epithelial growth factor receptor (EGFR)(n=131), vascular endothelial growth factor receptor 3 (VEGFR3)(n=142), NM23 (n=129), MRP (n=109), P170 (n=104), TS (n=143), Tubulin (n=133), ribonucleotide reductase M1 (RRM1)(n=131), ribonucleotide reductase M1 (COX2)(n=138), and TOPII (n=127). Only VEGFR3 expression was correlated with prognosis of the patients by univariate analysis, with 5-yrs survival rate being 77.6% and 65.0% (positive vs. negative) respectively (P=0.042). However, VEGFR3 was not an independent prognostic factor for this series of NSCLC patients in multivariate analysis. Conclusion These twelve IHC markers could not predict prognosis of NSCLC patients after surgery in our series

IGFBP1^hiWNT3A^lo Subtype in Esophageal Cancer Predicts Response and Prolonged Survival with PD-(L)1 Inhibitor

PD-(L)1 inhibitor could improve the survival of locally advanced esophageal cancer (ESCA) patients, but we cannot tailor the treatment to common biomarkers. WNT signaling activation was associated with primary resistance to immunotherapy. In this study, we used our two clinical cohorts (BJCH n = 95, BJIM n = 21) and three public cohorts to evaluate and verify a new immunotherapeutic biomarker based on WNT signaling in ESCA patients. Our findings showed that WNT signaling-related genes stratified TCGA patients into Cluster 1, 2, and 3, among which, Cluster 3 had the worst prognosis. The most up- and down-regulated genes in Cluster 3 were IGFBP1 and WNT3A. Further analysis validated that IGFBP1hiWNT3Alo ESCA patients had significantly poor RFS and OS in the TCGA and BJCH cohorts. Interestingly, IGFBP1hiWNT3Alo patients had a good response and prognosis with immunotherapy in three independent cohorts, exhibiting better predictive value than PD-L1 expression (signature AUC = 0.750; PD-L1 AUC = 0.571). Moreover, IGFBP1hiWNT3Alo patients may benefit more from immunotherapy than standard treatment (p = 0.026). Immune cell infiltration analysis revealed a significant increase in DC infiltration in IGFBP1hiWNT3Alo patients post-immunotherapy (p = 0.022), which may enhance immune response. The IGFBP1hiWNT3Alo signature could predict patients who benefited from PD-(L)1 inhibitor treatment and may serve as a biomarker in ESCA

Treatment Outcomes and Prognostic Factors of Pulmonary Metastasectomy for Bone and Soft Tissue Sarcoma: a High Volume Academic Institution Experience

Background and objective The bone and soft tissue sarcoma can metastasize to distant sites, most commonly the lungs. Some cases can be cured by radical metastasectomy, but its role, indication and prognostic factors remains controversial. The rarity of the disease combined with the diverse number of subtypes can make bone and soft tissue sarcomas very difficult to study. There are few randomized control studies or international high volume results, and such reports in China are seldom seen. The aim of this study is to investigate surgical treatment outcomes and prognostic factors of pulmonary metastatic bone and soft tissue sarcoma patients. Methods From January 2007 to December 2015, patients with bone and soft tissue sarcoma who underwent multimodality therapy including definitive surgery for the primary lesion and at least one pulmonary metastasectomy were enrolled in the retrospective study. All the relevant clinical variables were collected, and then statistically analyzed and interpreted with the aid of univariate and multivariate Cox proportional hazard regression method. Results Totally 155 pulmonary metastasectomies in 144 patients were analyzed. Incomplete R0 resection, a less than 1-year interval from a previous surgery, more than three detected nodules; and the summed maximum diameter of more than 45 mm for pulmonary metastases were independent prognostic indicators by multivariate analysis. Conclusion We suggest that metastatic bone and soft tissue sarcoma patients can benefit most from aggressive surgical intervention of pulmonary metastasectomy. Its prognostic factors include R0 resection, a longer interval from a previous surgery, smaller total number and total size of pulmonary metastases

Conversion of human umbilical cord mesenchymal stem cells in Wharton's jelly to dopamine neurons mediated by the Lmx1a and neurturin in vitro: potential therapeutic application for Parkinson's disease in a rhesus monkey model.

hUC-MSCs hold great promise in vitro neuronal differentiation and therapy for neurodegenerative disorders including Parkinson's disease. Recent studies provided that Lmx1α play an important role in the midbrain dopamine cells differentiation. Neurturin is desired candidate gene for providing a neuroprotective to DA neurons. In this study, we investigated a novel neuronal differentiation strategy in vitro with Lmx1α and NTN. We transferred these two genes to hUC-MSCs by recombinant adenovirus combined with Lmx1α regulatory factor and other inductor to improve the efficiency of inducing. Then those induced cells were implanted into the striatum and substantia nigra of MPTP lesioned hemi-parkinsonian rhesus monkeys. Monkeys were monitored by using behavioral test for six months after implantation. The result showed that cells isolated from the umbilical cord were negative for CD45, CD34 and HLA-DR, but were positive for CD44, CD49d, CD29. After those cells were infected with recombinant adenovirus, RT-PCR result shows that both Lmx1α and NTN genes were transcribed in hUC-MSCs. We also observed that the exogenous were highly expressed in hUC-MSCs from immunofluorescence and western blot. Experiments in vitro have proved that secretion NTN could maintain the survival of rat fetal midbrain dopaminergic neurons. After hUC-MSCs were induced with endogenous and exogenous factors, the mature neurons specific gene TH, Pitx3 was transcripted and the neurons specific protein TH, β-tubulinIII, NSE, Nestin, MAP-2 was expressed in those differentiated cells. In addition, the PD monkeys, transplanted with the induced cells demonstrated the animals' symptoms amelioration by the behavioral measures. Further more, pathological and immunohistochemistry data showed that there were neuronal-like cells survived in the right brain of those PD monkeys, which may play a role as dopaminergic neurons. The findings from this study may help us to better understand the inside mechanisms of PD pathogenesis and may also help developing effective therapy for Parkinson's disease

Exploration of Postoperative Follow-up Strategies for Early Staged NSCLC Patients on the Basis of Follow-up Result of 416 Stage I NSCLC Patients after Lobectomy

Background and objective Currently, there is no consensus on the follow-up strategy (follow-up time interval and content) of non-small cell lung cancer (NSCLC) in the world, and the relevant clinical evidence is also very limited. In this study, we aimed to summarize the recurrence/metastasis sites and timings of stage I NSCLC patients based on their follow-up data, aiming to provide a basis of follow-up time interval and content for this group of patients. Methods We retrospectively analyzed the 416 stage I NSCLC patients that underwent continuous anatomic lobectomy between Jan. 2000 to Oct. 2013 in our prospective lung cancer database. According to the recurrence/metastasis sites and timings, the long term follow-up time interval and content were explored. Results The 5-yr disease free survival (DFS) and overall survival (OS) in the whole group were 82.4% and 85.4%, respectively. There were 76 cases (18.3%) had recurrence/metastasis during follow-up, among which the most frequent site was pulmonary metastasis (21 cases, 5.0%), followed by brain metastasis (20 cases, 4.8%), bone metastasis (12 cases, 2.9%), and mediastinal lymph node metastasis (12 cases, 2.9%). Among the factors that could influence recurrence/metastasis, patients with pT2a suffered from a higher recurrence/metastasis rate compared to patients with pT1 (P=0.006), with 5-yr DFS being 73.8% and 87.3%, respectively (P=0.002), and the 5-yr OS being 77.7% and 90.3%, respectively (P=0.011). Conclusion The commonest recurrence/metastasis sites of stage I NSCLC after anatomic lobectomy are lung, brain and mediastinal lymph nodes, the risk of recurrence/metastasis within 2 years were equal to that between 3 years and 5 years. The follow-up frequencies and content within 2 years could be adjusted according to T stages

Analysis of Prolonged Hospitalizations (Longer than 7 days): 115 Lung Cancer Patients after Video Assistant Thoracic Surgery (VATS)

Background and objective Thoracoscopic surgery has gradually become the major procedure for lung cancer surgery in our department. Its characteristics are minimal trauma and quick recovery, which make approximately 90% of patients discharge from the hospital after surgery. However, the postoperative complications still happen now and then. We analyzed the patients who had been hospitalized for longer than 7 days after thoracoscopic lung cancer surgery, aiming to summarize the types and risk factors of complications, and improve postoperative safety of patients. Methods The data were come from the prospective database of Thoracic Surgery Unit One in Peking Cancer Hospital, and patients that underwent thoracoscopic pulmonary surgery between Jan. 2010 and Dec. 2014 with length of stay more than 7 days were included in the study. The classifications of the complications were investigated and graded as mild or severe complications according to modified Claviengrading, the relationship between clinical factors and degrees of complications was also analyzed. Results The hospitalization of 115 cases were longer than 7 days after surgery, accounting for 10.3% (115/1,112) of the whole patients that underwent surgery during the same period. Eighty-one cases had mild complications, accounting for 7.3% (81/1,112) of the whole cases that underwent surgery during the same period and 70.4% (81/115) of the cases with prolonged length of stay; the proportions of severe complications in both groups were 3.1% (34/1,112) and 29.6% (34/115), respectively; and the proportions of complications that caused perioperative deaths were 0.18% (2/1112) and 1.7% (2/115), respectively. Among all the postoperative complications, the most common was air leakage for more than 5 days after surgery, with a total of 20 cases (1.8% and 17.4%). The other common complications were: atelectasis (19 cases, 1.7% and 16.5%), pulmonary infection (18 cases, 1.6% and 15.7%), etc. The less common complications was bronchopleural fistula (4 cases, 0.36% and 3.5%) with very high risk, and 2 cases died perioperatively due to the combination of acute respiratory distresssyndrome (ARDS). In the clinical factors, only preoperative low pulmonary function (FEV1%<70%) was the potential risk factor for postoperative severe complications (45.8% vs 23.6%, P=0.038). There was no significant difference either regarding the 5 year disease free survival or the 5 year overall survival between mild complication group and severe complication group, with 5 year DFS being 52.2% and 51.9%, respectively (P=0.894) , and 5 year overall survival being 64.0% and 53.5%, respectively (P=0.673). Conclusion Continuous postoperative air leakage, atelectasis and pulmonary infections were the major causes for prolonged hospitalization after thoracoscopic surgery for lung cancer, and bronchopleural fistula was the most perilous complications. Patients with low preoperative pulmonary function were more likely to have severe postoperative complication, however, this would not influence the long term survival of the patients

The expression of neural-specific marker containing TH, β-tubulinIII, MAP-2, NSE, Nestin and Lmx1α in hUC-MSCs induced 21 days was analyzed by immunofluorescence.

<p>Scale bar: 100 µm.</p