Impulse oscillometry for detection of small airway dysfunction in subjects with chronic respiratory symptoms and preserved pulmonary function.

BACKGROUND: Subjects with chronic respiratory symptoms and preserved pulmonary function (PPF) may have small airway dysfunction (SAD). As the most common means to detect SAD, spirometry needs good cooperation and its reliability is controversial. Impulse oscillometry (IOS) may complete the deficiency of spirometry and have higher sensitivity. We aimed to explore the diagnostic value of IOS to detect SAD in symptomatic subjects with PPF. METHODS: The evaluation of symptoms, spirometry and IOS results in 209 subjects with chronic respiratory symptoms and PPF were assessed. ROC curves of IOS to detect SAD were analyzed. RESULTS: 209 subjects with chronic respiratory symptoms and PPF were included. Subjects who reported sputum had higher R5-R20 and Fres than those who didn't. Subjects with dyspnea had higher R5, R5-R20 and AX than those without. CAT and mMRC scores correlated better with IOS parameters than with spirometry. R5, R5-R20, AX and Fres in subjects with SAD (n = 42) significantly increased compared to those without. Cutoff values for IOS parameters to detect SAD were 0.30 kPa/L s for R5, 0.015 kPa/L s for R5-R20, 0.30 kPa/L for AX and 11.23 Hz for Fres. Fres has the largest AUC (0.665, P = 0.001) among these parameters. Compared with spirometry, prevalence of SAD was higher when measured with IOS. R5 could detect the most SAD subjects with a prevalence of 60.77% and a sensitivity of 81% (AUC = 0.659, P = 0.002). CONCLUSION: IOS is more sensitive to detect SAD than spirometry in subjects with chronic respiratory symptoms and PPF, and it correlates better with symptoms. IOS could be an additional method for SAD detection in the early stage of diseases.

Acute severe radiation pneumonitis among non-small cell lung cancer (NSCLC) patients with moderate pulmonary dysfunction receiving definitive concurrent chemoradiotherapy: Impact of pre-treatment pulmonary function parameters.

PURPOSE: Severe acute radiation pneumonitis (SARP) is a life-threatening complication of thoracic radiotherapy. Pre-treatment pulmonary function (PF) may influence its incidence. We have previously reported on the incidence of SARP among patients with moderate pulmonary dysfunction who received definitive concurrent chemoradiotherapy (dCCRT) for non-small cell lung cancer (NSCLC). METHODS: The clinical outcomes, dose-volume histograms (DVH), and PF parameters of 122 patients (forced expiratory volume in 1 s [FEV1%]: 60-69%) receiving dCCRT between 2013 and 2019 were recorded. SARP was defined as grade ≥3 RP occurring during or within 3 months after CCRT. Logistic regression, receiver operating characteristics curves (ROC), and hazard ratio (HR) analyses were performed to evaluate the predictive value of each factor for SARP. RESULTS: Univariate and multivariate analysis indicated that the ratio of carbon monoxide diffusing capacity (DLCO%; odds ratio [OR]: 0.934, 95% confidence interval [CI] 0.896-0.974, p = 0.001) and mean lung dose (MLD; OR: 1.002, 95% CI 1.001-1.003, p = 0.002) were independent predictors of SARP. The ROC AUC of combined DLCO%/MLD was 0.775 (95% confidence interval [CI]: 0.688-0.861, p = 0.001), with a sensitivity and specificity of 0.871 and 0.637, respectively; this was superior to DLCO% (0.656) or MLD (0.667) alone. Compared to the MLD-low/DLCO%-high group, the MLD-high/DLCO%-low group had the highest risk for SARP, with an HR of 9.346 (95% CI: 2.133-40.941, p = 0.003). CONCLUSION: The DLCO% and MLD may predict the risk for SARP among patients with pre-treatment moderate pulmonary dysfunction who receive dCCRT for NSCLC. Prospective studies are needed to validate our findings.

One-stage revision arthroplasty in a patient with ochronotic arthropathy accompanied by joint infection: A case report.

BACKGROUND: Ochronotic arthropathy (OcA) is a rare disease, which is caused by the accumulation of homogentisic acid in the joint. Patients with OcA have obvious joint pain and the disease progresses rapidly, eventually resulting in disability. Arthroplasty is an efficacious treatment in patients with OcA. However, when OcA patients have joint infection, is joint replacement an option? In the present report, we performed total knee arthroplasty in a patient with OcA and knee infection under the guidance of one-stage revision theory. CASE SUMMARY: A 64-year-old male was referred to our hospital due to severe left knee pain with limited mobility for 2 years. On physical examination, the patient was found to have dark brown pigmentation of the sclera and auricle. Laboratory test results showed elevations in C-reactive protein level (65.79 mg/L) and erythrocyte sedimentation rate (90.00 mm/h). The patient underwent debridement of the left knee joint, during which the cartilage surface of the knee joint was found to be black-brown in color. Bacterial culture of synovial fluid revealed Achromobacter xylosoxidans. We then carried out arthroplasty under the guidance of the theory of one-stage revision. After surgery, the patient's left knee joint pain disappeared and function recovered without joint infection. CONCLUSION: OcA accompanied by joint infection is rare. One-stage revision arthroplasty may be a treatment option for this disease.

International expert consensus on the management of bleeding during VATS lung surgery.

Intraoperative bleeding is the most crucial safety concern of video-assisted thoracic surgery (VATS) for a major pulmonary resection. Despite the advances in surgical techniques and devices, intraoperative bleeding is still not rare and remains the most common and potentially fatal cause of conversion from VATS to open thoracotomy. Therefore, to guide the clinical practice of VATS lung surgery, we proposed the International Interest Group on Bleeding during VATS Lung Surgery with 65 experts from 10 countries in the field to develop this consensus document. The consensus was developed based on the literature reports and expert experience from different countries. The causes and incidence of intraoperative bleeding were summarised first. Seven situations of intraoperative bleeding were collected based on clinical practice, including the bleeding from massive vessel injuries, bronchial arteries, vessel stumps, and bronchial stumps, lung parenchyma, lymph nodes, incisions, and the chest wall. The technical consensus for the management of intraoperative bleeding was achieved on these seven surgical situations by six rounds of repeated revision. Following expert consensus statements were achieved: (I) Bleeding from major vascular injuries: direct compression with suction, retracted lung, or rolled gauze is useful for bleeding control. The size and location of the vascular laceration are evaluated to decide whether the bleeding can be stopped by direct compression or by ligation. If suturing is needed, the suction-compressing angiorrhaphy technique (SCAT) is recommended. Timely conversion to thoracotomy with direct compression is required if the operator lacks experience in thoracoscopic angiorrhaphy. (II) Bronchial artery bleeding: pre-emptive clipping of bronchial artery before bronchial dissection or lymph node dissection can reduce the incidence of bleeding. Bronchial artery bleeding can be stopped by compression with the suction tip, followed by the handling of the vascular stump with energy devices or clips. (III) Bleeding from large vessel stumps and bronchial stumps: bronchial stump bleeding mostly comes from accompanying bronchial artery, which can be clipped for hemostasis. Compression for hemostasis is usually effective for bleeding at the vascular stump. Otherwise, additional use of hemostatic materials, re-staple or a suture may be necessary. (IV) Bleeding from the lung parenchyma: coagulation hemostasis is the first choice. For wounds with visible air leakage or an insufficient hemostatic effect of coagulation, suturing may be necessary. (V) Bleeding during lymph node dissection: non-grasping en-bloc lymph node dissection is recommended for the nourishing vessels of the lymph node are addressed first with this technique. If bleeding occurs at the site of lymph node dissection, energy devices can be used for hemostasis, sometimes in combination with hemostatic materials. (VI) Bleeding from chest wall incisions: the chest wall incision(s) should always be made along the upper edge of the rib(s), with good hemostasis layer by layer. Recheck the incision for hemostasis before closing the chest is recommended. (VII) Internal chest wall bleeding: it can usually be managed with electrocoagulation. For diffuse capillary bleeding with the undefined bleeding site, compression of the wound with gauze may be helpful.

Targeted therapy of esophageal squamous cell carcinoma: the NRF2 signaling pathway as target.

Esophageal squamous cell carcinoma (ESCC) is a deadly disease that requires extensive research. Here, we review the current understanding of the functions of the nuclear factor erythroid-derived 2-like 2 (NRF2) signaling pathway in the esophagus. Genomic data suggest that gene mutations and several other mechanisms result in NRF2 hyperactivation in human ESCC. As a consequence, NRF2high ESCC is more resistant to chemoradiotherapy and associated with poorer survival than NRF2low ESCC. Mechanistically, we believe NRF2, functioning as a transcription factor, causes an esophageal phenotype through regulation of gene transcription. We discuss metabolism, mitochondria, proteasomes, and several signaling pathways as downstream players that may contribute to an esophageal phenotype due to NRF2 hyperactivation. Finally, strategies are proposed to target the NRF2 signaling pathway for therapy of NRF2high ESCC.

Neoadjuvant chemotherapy followed by minimally invasive esophagectomy is safe and feasible for treatment of esophageal squamous cell carcinoma.

BACKGROUND: The advantage of neoadjuvant chemotherapy (NAC) followed by open esophagectomy for treatment of esophageal squamous cell carcinoma has been widely recognized. However, the safety and feasibility of NAC for patients receiving minimally invasive esophagectomy (MIE) remain controversial. The purpose of this study was to evaluate the potential impact of prior neoadjuvant chemotherapy on the clinical outcome of MIE by comparing two groups of patients, MIE alone and NAC plus MIE. METHODS: From May 2013 to July 2017, 124 patients with esophageal squamous cell carcinoma underwent MIE in our department, with 57 cases receiving NAC plus MIE and 67 cases receiving MIE alone. Perioperative parameters and short-term postoperative survival were compared between these two groups to evaluate the safety and feasibility of NAC given before MIE. RESULTS: The group with NAC plus MIE had slightly longer operating time, more blood loss, higher morbidity, increased chance of surgical intensive care unit stay, and longer surgical intensive care unit stay time than the group with MIE alone. However, there was no statistically significant difference between these two groups (P > 0.05). The number of lymph nodes harvested was similar in the two groups without significant difference (P > 0.05). The overall survival was not significantly different between these two groups either (P > 0.05), although before surgery the clinical stage of the group with NAC plus MIE was more advanced than the group with MIE alone. CONCLUSIONS: NAC followed by MIE is safe and feasible for treatment of esophageal squamous cell carcinoma. NAC does not negatively impact the therapeutic outcome of MIE.

[The Initial Experience of Video-assisted Thoracic Surgery Segmentectomy for Early Stage Lung Cancer].

BACKGROUND: Segmentectomy can retains more healthy lung tissue than lobectomy, but it remains controversial in oncology for early stage lung cancer. The aim of this study is to discuss the problems of video-assisted thoracic surgery (VATS) segmentectomy in early stage lung cancer, by analyzing the clinical and pathological data of 35 cases and reviewing the literature. METHODS: There were 35 patients who received segmentectomy by complete video-assisted thoracic surgery, from May 2013 to July 2017, in single operation group in the Third Hospital of Peking University. We analyzed the patient's clinical and pathological data, intraoperative and postoperative complications, lymph node number and metastasis its situation, and compared postoperative pathology and preoperative computed tomography (CT) imaging type. In 35 cases of segmentectomy, there were 11 males and 24 females, with an average age of 57.7 years old. The lesions located in the right upper lobe were 8 cases, in the right lower lobe were 8 cases, in the left upper lobe were 13 cases, in the left lower lobe were 6 cases. The mean maximum diameter of CT imaging was 12.7 mm, and the largest diameter of hilar and mediastinal lymph nodes was less than 10 mm. 23 of them were ground glass predominating and 12 were solid components predominating. RESULTS: All 35 cases were successfully completed VATS anatomical segmentectomy. The average operation time was 153 minutes, the amount of bleeding was 51 mL. There were 10 cases of air leakage after operation, all of which were not more than 3 days. There was contralateral atelectasis in 1 case, chylothorax in 1 case. The average length of hospitalization was 6.1 days. There was no other complications outpatient related to surgery, in 30 days after discharge. The pathological changes were as follow, 2 cases of metastatic tumor, 8 cases of benign lung disease and 25 cases of primary lung cancer. In the 25 cases of primary lung cancer, there were 14 cases of invasive lung adenocarcinoma (7 cases were groundglassopacity (GGO) predominating in CT imaging), 4 cases of micro-invasive adenocarcinoma (3 cases were GGO predominating in CT imaging), 6 cases of adenocarcinoma in situ (all were pure GGO in CT imaging), 1 case of lung squamous cell carcinoma (mainly composed of solid in CT imaging). An average of 7.2 lymph nodes were removed in 25 cases of lung cancer, and all lymph nodes had no metastasis. CONCLUSIONS: VATS anatomical segmentectomy is technically safe and reliable, and the indications for lung cancer need to be strictly controlled. Its advantages still need to be confirmed by prospective randomized controlled trials.

Publisher Correction: Global characterization of T cells in non-small-cell lung cancer by single-cell sequencing.

In the version of this article originally published, the P statistic described in Fig. 3d was incorrect. It was described as "P < 22 × 10-16". It should have been "P < 2.2 × 10-16". Also, the "CD8+ Treg" label in Fig. 4f was incorrect. It should have been "CD4+ Treg". The errors have been corrected in the HTML and PDF versions of this article.

Global characterization of T cells in non-small-cell lung cancer by single-cell sequencing.

Cancer immunotherapies have shown sustained clinical responses in treating non-small-cell lung cancer1-3, but efficacy varies and depends in part on the amount and properties of tumor infiltrating lymphocytes4-6. To depict the baseline landscape of the composition, lineage and functional states of tumor infiltrating lymphocytes, here we performed deep single-cell RNA sequencing for 12,346 T cells from 14 treatment-naïve non-small-cell lung cancer patients. Combined expression and T cell antigen receptor based lineage tracking revealed a significant proportion of inter-tissue effector T cells with a highly migratory nature. As well as tumor-infiltrating CD8+ T cells undergoing exhaustion, we observed two clusters of cells exhibiting states preceding exhaustion, and a high ratio of "pre-exhausted" to exhausted T cells was associated with better prognosis of lung adenocarcinoma. Additionally, we observed further heterogeneity within the tumor regulatory T cells (Tregs), characterized by the bimodal distribution of TNFRSF9, an activation marker for antigen-specific Tregs. The gene signature of those activated tumor Tregs, which included IL1R2, correlated with poor prognosis in lung adenocarcinoma. Our study provides a new approach for patient stratification and will help further understand the functional states and dynamics of T cells in lung cancer.

[Surgical Treatment of Small Pulmonary Nodules Under Video-assisted Thoracoscopy 
(A Report of 129 Cases)].

BACKGROUND: The development of image technology has led to increasing detection of pulmonary small nodules year by year, but the determination of their nature before operation is difficult. This clinical study aimed to investigate the necessity and feasibility of surgical resection of pulmonary small nodules through a minimally invasive approach and the operational manner of non-small cell lung cancer (NSCLC). METHODS: The clinical data of 129 cases with pulmonary small nodule of 10 mm or less in diameter were retrospectively analyzed in our hospital from December 2013 to November 2016. Thin-section computed tomography (CT) was performed on all cases with 129 pulmonary small nodules. CT-guided hook-wire precise localization was performed on 21 cases. Lobectomy, wedge resection, and segmentectomy with lymph node dissection might be performed in patients according to physical condition. RESULTS: Results of the pathological examination of 37 solid pulmonary nodules (SPNs) revealed 3 primary squamous cell lung cancers, 3 invasive adenocarcinomas (IAs), 2 metastatic cancers, 2 small cell lung cancers (SCLCs), 16 hamartomas, and 12 nonspecific chronic inflammations. The results of pathological examination of 49 mixed ground glass opacities revealed 19 IAs, 6 micro invasive adenocarcinomas (MIAs), 4 adenocarcinomas in situ (AIS), 1 atypical adenomatous hyperplasia (AAH), 1 SCLC, and 18 nonspecific chronic inflammations. The results of pathological examination of 43 pure ground glass opacities revealed 19 AIS, 6 MIAs, 6 IA, 6 AAHs, and 6 nonspecific chronic inflammations. Wedge resection under video-assisted thoracoscopic surgery (VATS) was performed in patients with 52 benign pulmonary small nodules. Lobectomy and systematic lymph node dissection under VATS were performed in 33 patients with NSCLC. Segmentectomy with selective lymph node dissection, wedge resection, and selective lymph node dissection under VATS were performed in six patients with NSCLC. Two patients received secondary lobectomy and systematic lymph node dissection under VATS because of intraoperative frozen pathologic error that happened in six cases. Two cases of N2 lymph node metastasis were found in patients with SPN of IA. CONCLUSIONS: Positive surgical treatment should be taken on patients with persistent pulmonary small nodules, especially ground glass opacity, because they have a high rate of malignant lesions. During the perioperative period, surgeons should fully inform the patients and family members that error exist in frozen pathologic results to avoid medical disputes.

[Clinical Study of Surgical Treatment of Non-small Cell Lung Cancer 
10 mm or Less in Diameter Under Video-assisted Thoracoscopy].

BACKGROUND: The reasonable operational manner of non-small cell lung cancer (NSCLC) in early stage is in dispute. This clinical study is to investigate the operational manner of NSCLC 10 mm or less in diameter. METHODS: The clinical datas of 46 cases with NSCLC 10 mm or less in diameter were retrospectively analyzed in our hospital from July 2013 to March 2016. Thin-section computed tomography (CT) was done on all cases with 46 pulmonary nodules (5 solid nodules, 23 mGGOs and 18 pGGOs). Lobectomy, wedge resection and segmentectomy with lymph node dissection may be performed in patients according to age or heart and lung function. CT-guided Hook-wire precise localization was done on 7 cases. RESULTS: Lobectomy and systematic lymph node dissection under video-assisted thoracic surgery (VATS) were performed in patients with 23 pulmonary nodules (15 mGGOs, 4 pGGOs and 4 solid nodules ), among wich, only one patient with N2 lymph node matastasis was found. Wedge resection and selective lymph node dissection under VATS were done in patients with 5 pulmonary nodules (2 mGGOs and 3 pGGOs), and segmentectomy and selective lymph node dissection under VATS were done in patients with 4 pulmonary nodules (2 mGGOs and 2 pGGOs), among wich, no patient with lymph node matastasis was found. CT-guided Hook-wire precise localization was done successfully on 7 cases. CONCLUSIONS: Usually NSCLC with pGGO and mGGO nodules 10 mm or less in diameter has no lymph node metastasis, therefore, systematic lymph node dissection may be not necessary. Selective lymph node dissection or systematic lymph node dissection should be performed in patients with solid nodules 10 mm or less in diameter. Wedge resection and segmentectomy may be performed in patients with advanced age or lower heart and lung function. The preoperative CT-guided Hook-wire localization for pulmonary nodules particularly for GGOs is an effective and safe technique to assist VATS resection of the GGOs.

[Computed Tomography Guided Hook-wire Precise Localization and Minimally Invasive Resection of Pulmonary Nodules].

BACKGROUND AND OBJECTIVE: Localization of pulmonary ground glass nodule is the technical difficulty of minimally invasive operation resection. The aim of this study is to evaluate the value of computed tomography (CT)-guided Hook-wire precise localization in resection of pulmonary nodules by video-assisted thoracoscopic surgery (VATS) as well as to discuss the necessity and feasibility of surgical resection of GGOs through a minimally invasive approach. METHODS: CT-guided Hook-wire precise localization and wedge resection was done on 25 cases with 26 pulmonary nodules by VATS from May 2013 to June 2015. The efficacy of localization was evaluated in terms of procedure time, VATS success rate, and associated complications of localization. RESULTS: All the 26 pulmonary nodules (6 solid nodules and 20 GGOs ) of 25 patients (10 males and 15 females) were preoperatively detected and localized with Hook-wire under CT guidance. Nodule diameters ranged from 5 mm-20 mm (mean: 8 mm). The distance of lung lesions from the nearest pleural surfaces ranged within 5 mm-30 mm (mean: 14 mm). All resections of lesions guided by the Hook-wire were successfully performed by VATS (success rate: 100%). The mean procedure time for the CT-guided Hook-wire localization was 10 min (range: 5 min-10 min). The mean procedure time for VATS wedge resection was 20 min (range: 15 min-40 min). The mean hospital time was 4 d (range: 3 d-6 d). The major complication of CT-guided Hook-wire localization was mild pneumothorax in 4 patients, but no one needed chest tube drainage. Wedge resection was performed successfully in all cases. The dislocation of Hook-wire was found in only one patient during the operation, but the lesion was still successfully resected under VATS. Results of pathological examination of 16 mGGOs revealed 8 primary lung cancers and 8 nonspecific chronic inflammations. Results of pathological examination of 4 pGGOs revealed 1 primary lung cancers, 1 atypical adenomatous hyperplasia (AAH), and 2 nonspecific chronic inflammations. CONCLUSIONS: The preoperative CT-guided Hook-wire localization for pulmonary nodules particularly for GGOs is an effective and safe technique to assist VATS resection of the nodules. It can increase the ratio of lung wedge resection with little complications and may be better used in clinical diagnosis and treatment of small pulmonary nodules with VATS. Lung mGGOs carry a high risk of malignancy. Aggressive surgical resection of these mGGOs is necessary and feasible.

Open three-stage transthoracic oesophagectomy versus minimally invasive thoraco-laparoscopic oesophagectomy for oesophageal cancer: protocol for a multicentre prospective, open and parallel, randomised controlled trial.

INTRODUCTION: Oesophageal cancer is the eighth most common cause of cancer worldwide. In 2009 in China, the incidence and death rate of oesophageal cancer was 22.14 per 100 000 person-years and 16.77 per 100 000 person-years, respectively, the highest in the world. Minimally invasive oesophagectomy (MIO) was introduced into clinical practice with the aim of reducing the morbidity rate. The mechanisms of MIO may lie in minimising the reaction to surgical injury and inflammation. There are some randomised trials regarding minimally invasive versus open oesophagectomy, with 100-850 subjects enrolled. To date, no large randomised controlled trial comparing minimally invasive versus open oesophagectomy has been reported in China, where squamous cell carcinoma predominated over adenocarcinoma of the oesophagus. METHODS AND ANALYSIS: This is a 3 year multicentre, prospective, randomised, open and parallel controlled trial, which aims to compare the effectiveness of minimally invasive thoraco-laparoscopic oesophagectomy to open three-stage transthoracic oesophagectomy for resectable oesophageal cancer. Group A patients receive MIO which involves thoracoscopic oesophagectomy and laparoscopic gastric mobilisation with cervical anastomosis. Group B patients receive the open three-stage transthoracic oesophagectomy which involves a right thoracotomy and laparotomy with cervical anastomosis. Primary endpoints include respiratory complications within 30 days after operation. The secondary endpoints include other postoperative complications, influences on pulmonary function, intraoperative data including blood loss, operative time, the number and location of lymph nodes dissected, and mortality in hospital, the length of hospital stay, total expenses in hospital, mortality within 30 days, survival rate after 2 years, postoperative pain, and health-related quality of life (HRQoL). Three hundred and twenty-four patients in each group will be needed and a total of 648 patients will finally be enrolled into the study. ETHICS AND DISSEMINATION: The study protocol has been approved by the Institutional Ethics Committees of all participating institutions. The findings of this trial will be disseminated to patients and through peer-reviewed publications and international presentations. TRIAL REGISTRATION NUMBER: NCT02355249.