Blood Coagulation-Inspired Fibrin Hydrogel for Portable Detection of Thrombin Based on Personal Glucometer.

As one of the biomarkers of coagulation system-related diseases, the detection of thrombin is of practical importance. Thus, this study developed a portable biosensor based on a personal glucometer for rapid detection of thrombin activity. Fibrinogen was used for the detection of thrombin, and the assay principle was inspired by the blood coagulation process, where thrombin hydrolyzes fibrinogen to produce a fibrin hydrogel, and the amount of invertase encapsulated in the fibrin hydrogel fluctuates in accordance with the activity of thrombin in the sample solution. The quantitative assay is conducted by measuring the amount of unencapsulated invertase available to hydrolyze the substrate sucrose, and the signal readout is recorded using a personal glucometer. A linear detection range of 0-0.8 U/mL of thrombin with a limit of detection of 0.04 U/mL was obtained based on the personal glucometer sensing platform. The results of the selectivity and interference experiments showed that the developed personal glucometer sensing platform is highly selective and accurate for thrombin activity. Finally, the reliability of the portable glucometer method for rapid thrombin detection in serum samples was investigated by measuring the recovery rate, which ranged from 92.8% to 107.7%. In summary, the fibrin hydrogel sensing platform proposed in this study offers a portable and versatile means for detecting thrombin using a personal glucometer. This approach not only simplifies the detection process, but also eliminates the need for large instruments and skilled operators, and substantially reduces detection costs.

Lymph node dissection in small-sized pulmonary metastasectomy: Impact on the long-term survival.

INTRODUCTION: Pulmonary metastasectomy has been clarified in improving long-term survival in most primary malignancies with pulmonary metastasis, while the role of additional lymph node dissection remained controversial. We aimed to investigate the prognosis of lymph node involvement and identify the role of lymph node dissection during pulmonary metastasectomy in a real-world cohort. METHODS: We identified patients diagnosed with pulmonary metastases with ≤3 cm in size and received pulmonary metastasectomy between 2004 and 2017 in the Surveillance, Epidemiology, and End Results database. We compared the survival via Kaplan-Meier analysis and propensity score matching method, and the multivariable analysis was conducted by cox regression analysis. RESULTS: A total of 3452 patients were included, of which 2268(65.7%) received lymph node dissection, and the incidence of node-positive was 11.3%(256/2268). In total, the median overall survival was 62.8 months(interquartile range, 28.6-118.9 months), and the lymph node involvement was referred to an impaired survival compared to node-negative diseases(5-year overall survival rate, 58.0% versus 38.6%), with comparable survival between N1 and N2 diseases(P = 0.774). Lymph node dissection was associated with improved survival(HR = 0.80; 95%CI, 0.71-0.90; P < 0.001), and the survival benefits remained regardless of age, sex, the number of metastases, and surgical procedures, even in those with node-negative diseases. At least eight LNDs might lead to a significant improvement in survival, and additional survival benefits might be limited with additional dissected lymph nodes. CONCLUSIONS: Lymph node involvement was associated with impaired survival, and lymph node dissection during pulmonary metastasectomy could improve long-term survival and more accurate staging.

En bloc resection of an extremely giant mediastinal immature teratoma with somatic-type malignancy: A case report with a brief review of the literature.

Primary mediastinum immature teratoma with somatic-type malignant transformation (SM) is extremely rare, and the clinical prognosis is poor. Immature teratoma with SM is difficult to eradicate by chemotherapy due to poor sensitivity; therefore, surgical resection is recommended whenever possible because it may offer better survival.

The impact of previous extrapulmonary malignancies on survival of surgically treated primary lung cancer: a comprehensive systematic review and meta-analysis.

Whether a history of previous extrapulmonary malignancies had an impact on the survival of surgically treated primary lung cancer patients remains unknown. To better answer this question, we, therefore, conducted the first meta-analysis to compare the survival of lung cancer patients after surgical resection with previous extrapulmonary malignancies and those without. We systematically searched PubMed, Embase, and the Cochrane Library to identify relevant studies up to April 1, 2022. Data for analysis were obtained directly from the text results or calculated from the Kaplan-Meier survival curve, which mainly included 5-year overall survival (OS) and recurrence-free survival (RFS). Pooled hazard ratios (HRs) and 95% confidence intervals (CIs) were analyzed by the fixed-effect model test or standard random-effect model test depending on the heterogeneity of the included studies. The Q-test and I2-test were used to assess heterogeneity. Sensitivity analysis was performed to examine the stability of the pooled results. We finally included 7 retrospective studies consisting of 19,723 surgically treated primary lung cancer patients with (7.7%) or without (92.3%) previous extrapulmonary malignancies. The final results showed that lung patients with previous extrapulmonary malignancies had an inferior OS (HR 1.18, 95% CI [1.07, 1.31], P = 0.001) than those without, but no significant difference in RFS (HR 1.15, 95% CI [0.89-1.47], P = 0.29) was observed between the two groups. Moreover, when only focusing on stage-I primary lung cancer patients with or without previous extrapulmonary malignancies, the results still held true (OS: HR 1.39, 95% CI [1.04, 1.85], P = 0.02; RFS: HR 1.10, 95% CI [0.82-1.49], P = 0.51, respectively). No significant heterogeneities or publication bias were observed among these studies. Our meta-analysis showed that surgically treated primary lung cancer patients with a previous extrapulmonary cancer history had a worse overall survival than those without. However, a history of previous extrapulmonary cancer was not associated with postsurgical lung cancer recurrence, and more large-scale prospective studies should be encouraged to update our conclusions.

Surgical resection versus radiotherapy for clinical stage IA lung cancer ≤1 cm in size: A population-based study.

OBJECTIVE: With the increasing incidence of stage IA lung cancer ≤1 cm in size, the optimal primary treatment remains to be controversial, and thus, we compared the survival of these patients treated with radiotherapy, wedge resection, segmentectomy, or lobectomy in a large population. METHODS: We identified patients with stage IA lung cancer ≤1 cm in size between 2004 and 2015 in the Surveillance, Epidemiology, and End Results (SEER) database. We compared the overall survival (OS) via Kaplan-Meier analysis and conducted Cox regression analysis via propensity score matching (PSM) method to identify the relative hazard ratio (HR) and difference of OS among these treatments in the subgroup stratified by four variables (age, total number of tumors, pathological grade, and histology). RESULTS: A total of 5435 patients were included with a median age of 68 years (range, 6-94 years), of which 2131 (39.2%) were male, and 3510 (64.6%) were adenocarcinoma. The 5-year OS rate was 67.1%, 34.5%, 61.6%, 72.1%, and 75.0% for the entire study population, radiotherapy, wedge resection, segmentectomy, and lobectomy, respectively. In PSM analysis, wedge resection and segmentectomy were all superior to radiotherapy (P < 0.001), and segmentectomy was superior to wedge resection (P = 0.043), while segmentectomy was comparable with lobectomy (P = 0.058). In patients with multiple tumors, radiotherapy brought similar survival to surgery (wedge resection versus radiotherapy, P = 0.323; segmentectomy versus radiotherapy, P = 0.170; lobectomy versus radiotherapy, P = 0.796). CONCLUSIONS: Among stage IA lung cancer with ≤1 cm, segmentectomy and lobectomy were identified as the potential effective treatments, with segmentectomy more preferred, while radiotherapy would be recommended in those with multiple tumors, which requires further verification.

The safety and feasibility of preoperative induction therapy of Savolitinib in non-small cell lung cancer patients with MET exon 14 skipping mutation.

PURPOSE: Neoadjuvant therapy followed by surgical resection is one of the preferred treatment option for locally advanced non-small cell lung cancer (NSCLC). For patients with mesenchymal-epithelial transition (MET) factor exon 14 skipping (METex14) mutations, the use of MET-tyrosine kinase inhibitors (TKIs) showed high efficiency and reduced toxicity compared with first-line standard chemotherapy. However, it is unknown whether preoperative induction targeted therapy of MET-TKIs is feasible and safe. METHODS: Here, we reported 3 cases of locally advanced unresectable NSCLC with METex14 mutations receiving induction therapy of MET-TKI savolitinib as first-line therapy or second-line therapy when they experienced disease progression after preoperative chemotherapy. RESULTS: All these 3 patients achieved significant tumor size shrinkage and their unresectable tumors became resectable after the treatment of savolitinib. No serious adverse events were observed during the treatment. They recovered well postoperatively, and no significant events were identified. CONCLUSIONS: Preoperative induction treatment with MET-TKI savolitinib showed its safety and effectiveness and may be an alternative option for neoadjuvant therapy for NSCLC patients with METex14 mutations.

Lobe-specific lymph node dissection in early-stage non-small-cell lung cancer: An overview.

Lymph node dissection is a vital part of surgical treatment for early-stage non-small cell lung cancer (NSCLC). Lobectomy with systematic lymph node dissection (SLND) still remains the gold standard surgical treatment for early-stage NSCLC patients. However, an increasing number of studies have demonstrated that lobe-specific lymph node dissection (L-SLND) can be used as an alternative therapy for SLND in carefully selected patients with early-stage NSCLC. However, there are no currently available evidences of review summarizing the role of L-SLDN in treating early-stage NSCLC. Therefore, we performed this literature review by summarizing the existing literatures on the lymph node drainage pattern, definition, scope and role of L-SLND in patients with early-stage NSCLC, aiming to provide evidence for the application of L-SLND in patients with early-stage NSCLC.

Does the division of the inferior pulmonary ligament in upper lobectomy result in improved short-term clinical outcomes and long-term survival?

A best evidence topic in thoracic surgery was written according to a structured protocol. The question addressed was 'Does the division of the inferior pulmonary ligament (IPL) in upper lobectomy result in improved short-term clinical outcomes and long-term survival?'. Altogether 43 papers were found using the reported search, of which 6 studies represented the best evidence to answer the clinical question, including a previous best evidence topic study, a meta-analysis and 4 retrospective cohort studies. The author, journal, date and country of publication, patient group studied, study type and relevant outcomes and results of these papers are tabulated. Most of the enrolled studies reported that there is no significant difference between the division groups and the preservation groups in terms of drainage time, drainage volume, postoperative dead space and complications. While 3 cohort studies revealed unfavoured postoperative pulmonary function in the division groups, including lung volume, forced vital capacity and forced expiratory volume in 1 s. The previous meta-analysis and a recent cohort study also found that the division of IPL might lead to increased bronchus angle change or torsion. Moreover, 2 cohort studies found that the division of IPL could not improve the long-term survival of patients undergoing upper lobectomy. Current evidence showed that dividing the IPL could not result in clinical benefits but might lead to decreased pulmonary function instead. Therefore, we recommended not dissecting the IPL routinely during upper lobectomy.

Is video-assisted thoracoscopic surgery comparable with thoracotomy in perioperative and long-term survival outcomes for non-small-cell lung cancer after neoadjuvant treatment?

A best evidence topic in thoracic surgery was written according to a structured protocol. The question addressed was 'Is video-assisted thoracoscopic surgery comparable with thoracotomy in perioperative and long-term survival outcomes for patients with non-small cell lung cancer following neoadjuvant therapy intended for anatomical lung resection?'. Altogether 655 papers were found using the reported search, of which 12 studies represented the best evidence to answer the clinical question. The author, journal, date and country of publication, patient group studied, study type and relevant outcomes and results of these papers are tabulated. Almost all of the enrolled cohort studies reported that video-assisted thoracoscopic surgery (VATS) was comparable with thoracotomy in negative surgical margin rate, postoperative mortality, complication rate, overall survival and disease-free survival. Moreover, 7 studies found patients in the VATS group had a significantly shorter hospital stay. Furthermore, in these well-matched cohort studies (6 studies), it still held true that VATS was comparable with thoracotomy in long-term prognosis with enhanced recovery. However, the issue regarding surgical radicality and intraoperative conversion to thoracotomy still should be noted carefully among these patients receiving VATS surgery because all the current available evidence was retrospective based on relatively small sample sizes. Nevertheless, thoracic surgeons should not consider VATS inferior to thoracotomy for patients after neoadjuvant treatment. VATS surgery could be an alternative for selected patients with locally advanced but relatively small, peripheral, fewer positive N2 lymph nodes and non-squamous NSCLC intended for anatomic lung resection.

Characteristics and prognosis of primary pulmonary osteosarcoma: a pooled analysis.

BACKGROUND: Primary pulmonary osteosarcoma (PPOS) is an uncommon malignancy originating from the lung with low incidence, and its clinical characteristics and prognosis have not been systematically reported. Therefore, we aimed to recognize the prognostic factors and constructed a survival prediction model for PPOS. METHODS: We collected the data from the Surveillance, Epidemiology, and End Results database and systematic review of previous studies. Demographical and clinical characteristics, radiographic manifestations, treatment modalities, and prognosis were analyzed. A prediction model via nomogram was constructed and then evaluated by the concordance index (C-index) and the receiver operating characteristic (ROC) curve. RESULTS: A total of 49 cases were included for analysis with a median age of 67 years old (range 33-94 years), of which 32 (65.3%) were male. The median size was 6 cm (range 1.8-25 cm), and the median overall survival (OS) was eight months (interquartile range 4.5-12 months) with a 1-year OS rate of 30.8%. Tumor size over 7 cm (hazard ratio [HR] = 2.98; P = 0.018) and those without microscopic findings of osteoid found in the tumors (HR = 2.11; P = 0.048) were referred to a poor OS, while surgery was associated with an improved OS (HR = 0.20; P < 0.001). The C-index of the nomogram prediction model was 0.771, and the area under curve, sensitivity and specificity of the ROC curve were 0.818, 0.848 and 0.800, respectively. CONCLUSIONS: Patients with PPOS had a poor prognosis, and tumor size was mostly prognostic. Surgery seemed to be an effective treatment, and the prediction model with a nomogram in our study could effectively predict the prognosis of patients with PPOS.

LobE-Specific lymph node diSsectiON for clinical early-stage non-small cell lung cancer: protocol for a randomised controlled trial (the LESSON trial).

INTRODUCTION: Lung cancer was the most common malignancy and the leading cause of cancer-related death in China or worldwide, and surgery is still the preferred treatment for early-stage non-small cell lung cancer (NSCLC). The pattern of lymph node metastasis was found potentially lobe specific, and thus, lobe-specific lymph node dissection (L-SLND) was proposed to be an alternative to systematic lymph node dissection (SLND) for the treatment of early-stage NSCLC. METHODS AND ANALYSIS: The LobE-Specific lymph node diSsectiON trial is a single-institutional, randomised, double-blind and parallel controlled trial to investigate the feasibility of L-SLND in clinically diagnosed stage IA1-2 NSCLC with ground-glass opacity components (≥50%). The intraoperative frozen section examination of surgical tissues confirms the histological type of NSCLC. We hypothesise that L-SLND (experimental group) is not inferior to SLND (control group) and intend to include 672 participants for the experimental group and 672 participants for the control group with a follow-up duration of 60 months. The primary outcomes are 5-year disease-free survival and 5-year overall survival. The secondary outcomes are metastatic lymph node ratio, postoperative complication incidence and mortality, duration of operation, duration of anaesthesia (min), the volume of bleeding (mL) and drainage volume. The intention-to-treat analysis would be performed in the trial. ETHICS AND DISSEMINATION: This trial was approved by the ethics committee on biomedical research, West China Hospital of Sichuan University (2021-332). Informed consent would be obtained from all participants, and dissemination activities would include academic conference presentations and peer-reviewed publications. TRIAL REGISTRATION NUMBER: This trial was registered in the Chinese Clinical Trial Registry, ChiCTR2100048415.

Intraoperative conversion from video-assisted thoracoscopic lobectomy to thoracotomy for non-small-cell lung cancer: Does it have an impact on long-term survival?

A best evidence topic in thoracic surgery was written according to a structured protocol. The question addressed was whether intraoperative conversions to thoracotomy have an impact on long-term survival for patients with non-small-cell lung cancer who underwent video-assisted thoracoscopic lobectomy initially. A total of 461 papers were found using the reported search, of which 6 retrospective cohort studies represented the best evidence to answer the clinical question. The authors, date of publication, journal, country of the authors, patient group, study type, relevant outcomes and results of these papers were tabulated. Five cohort studies clarified that conversion did not compromise long-term survival, whereas 1 cohort study reported worse long-term outcomes after conversion to thoracotomy. However, the limited samples, different characteristics between groups and selection bias due to inherent design made it difficult to make a conclusion. Based on the current evidence, we concluded that intraoperative conversion from video-assisted thoracoscopic surgery (VATS) to thoracotomy for non-small-cell lung cancer might not impact long-term survival compared to a successful VATS lobectomy. In-hospital mortality might not be prejudiced, whereas longer hospitalizations were observed. However, whether conversion would adversely affect postoperative complication rates remained unclear because of the conflicting results. Moreover, 3 studies reported no statistical differences in short- and long-term survival between emergency and non-emergency conversions. Therefore, we suggest that thoracic surgeons should not hesitate to convert VATS into thoracotomy in the case of blood vessel injury or difficult hilum.

Wedge Resection vs. Stereotactic Body Radiation Therapy for Clinical Stage I Non-small Cell Lung Cancer: A Systematic Review and Meta-Analysis.

Background: Whether wedge resection or stereotactic body radiation therapy (SBRT) has better effectiveness in treatment of clinical stage I non-small cell lung cancer (NSCLC) patients remains unclear. Here we conducted the first meta-analysis to directly compare the survival outcomes of clinical stage I NSCLCs treated with wedge resection and SBRT. Methods: We systematically searched studies from PubMed, Embase, and Corchrane Library up to October 1, 2021. Data for analysis mainly included overall survival (OS) and disease-free survival (DFS), which were obtained directly from the text results or calculated from the Kaplan-Meier survival curve. We used the standard random-effect model test (DerSimonian and Laird method) to analyze the pooled hazard ratios (HRs) and 95% confidence intervals (CIs). The Q-test and I 2-test were used to assess heterogeneity. The stability of pooled HRs was examined by sensitivity analysis. Results: Six retrospective studies with a total of 11,813 clinical stage I NSCLCs who received wedge resection or SBRT were included. The results showed that patients receiving wedge resection had a significantly better OS (HR = 1.20, 95% CI = [1.07, 1.34], P = 0.002) than those with SBRT, but no significant difference of DFS (HR 1.53, 95% CI = [0.83-2.83], P = 0.17) was observed. There was no significant heterogeneity during our analysis, but there may be potential publication bias among these studies. Conclusions: Our meta-analysis showed that clinical stage I NSCLCs treated with wedge resection had superior OS than those treated with SBRT. However, more prospective clinical trials should be well-designed to evaluate the optimal treatment modality of early-stage NSCLCs.

Initial treatment of early-stage small-sized non-small cell lung cancer for octogenarians: a population-based study.

The objectives of this study is to figure out the appropriate initial treatment and criteria for clinical decision for early-stage small-sized non-small cell lung cancer (NSCLC) among octogenarians. Elderly patients (≥80 years) with stage I NSCLC (<3 cm) were identified between 2004 and 2015 in the Surveillance, Epidemiology, and End Results database. Patients were divided into four cohorts regarding treatment modalities, and overall survival and cancer-specific survival were evaluated via Kaplan-Meier analysis and Cox proportional hazard model. The propensity score matching method was introduced in the subgroup analysis stratified by four clinical characteristics to identify the preferable treatment. A total of 7861 patients were included with a median overall survival of 43 months (range 1-155 months). In younger patients (80-85 years), lobectomy was superior in improving the survival (versus segmentectomy, HR = 0.68, 95%CI 0.55-0.84; versus wedge resection, HR = 0.77; 95%CI 0.67-0.88). While in those over 85 years, lobectomy was superior to wedge resection (HR = 0.72; 95%CI 0.53-0.98), and all other treatments were comparable. As stratified by T stage in those over 85 years, lobectomy was superior to wedge resection (P = 0.023) for T1 disease, and the four treatments were all comparable in overall survival for T2 disease. In conclusions, the favored treatment of early stage NSCLC for octogenarians may be evaluated by age and T stage. Lobectomy might be preferred in patients between 80 and 85 years whenever possible. Among those over 85 years, radiotherapy might lead to a comparable prognosis and could be recommended as the prior treatment, while should surgery be recommended, lobectomy might be preferred for T1 disease and wedge resection for T2 disease.