Comparison of B cells' immune response induced by PEDV virulent and attenuated strains.

Porcine epidemic diarrhea virus (PEDV) is an acute, highly contagious enterovirus that infects pigs of all ages. The B cells are important for antigen presentation, antibody production, and cytokine secretion to resist infection. However, the role of B cells in PEDV infection remains unclear. In this study, the effects of PEDV virulent (QY2016) and attenuated strains (CV777) on B cells sorted from neonatal piglets, nursery piglets, and gilts were investigated. The results showed that PEDV-QY2016 and PEDV-CV777 could significantly increase the expression of CD54 and CD27 in B cells from neonatal piglets. The percentages of CD80, MHC II, and IgM expressed on neonatal piglet B cells infected with PEDV-QY2016 were significantly lower than those expressed on the B cells infected with PEDV-CV777. Both PEDV-QY2016 and PEDV-CV777 could stimulate IFN-α and GM-CSF secretions in neonatal piglet B cells; IL-1, IFN-α, and IL-4 secretion in nursery piglet B cells; and IL-1, TGF-ß secretion, and GM-CSF in gilt B cells. Furthermore, both PEDV-QY2016 and PEDV-CV777 could induce the secretion of IgA, IgM, and IgG in nursery piglet B cells but could not induce the secretion of IgA, IgM, and IgG in neonatal piglet B cells. The secretion of IgA, IgM, and IgG was significantly higher by the PEDV-CV777 strains infected B cells than those by the PEDV-QY2016 strains infected gilt B cells. In conclusion, the surface molecule expression, cytokine secretion, and antibody production of B cells induced by PEDV are closely related to the ages of pigs and the virulence of the PEDV strain.

Effects of porcine epidemic diarrhea virus infection on CD21+ B cells activation.

Porcine epidemic diarrhea virus (PEDV) is a devastating pathogen of acute- gastrointestinal infectious diseases, which can cause vomiting, diarrhea, dehydration and high morbidity and mortality among neonatal piglets. Humoral immunity plays a vital role in the host anti-PEDV infection process, but the mechanism of PEDV-induced B-cell immune response remains unknown. In this study, the effects of PEDV infection on CD21+ B cell activation were systematically analyzed through animal experiments. Enzyme-linked immunosorbent assays (ELISA) revealed that low levels of serum-specific IgA, IgM, or IgG were detected in piglets after PEDV infection, respectively. Serum interleukin (IL)-6 levels increased significantly at 4 d after infection, and the levels of IL-4, B-cell activating factor (BAFF), interferon (IFN)-γ, transforming growth factor (TGF)-ß and IL-10 decreased at 7 d after infection. Fluorescence-activated cell sorting (FACS) showed that expression levels of CD21, MHC Ⅱ, CD40, and CD38 on B cell surfaces were significantly higher. In contrast, the proportions of CD21+IgM+ B cells were decreased in peripheral blood mononuclear cells (PBMCs) from the infected piglets. No differences were found in the percentage of CD21+CD80+ and CD21+CD27+ B cells in PBMCs from the infected piglets. In addition, the number of CD21+B cells in PBMCs stimulated with PEDV in vitro was significantly lower. No significant change in the mRNA expression of BCR molecules was found while the expression levels of paired immunoglobulin-like receptor B (PIR-B), B cell adaptor molecule of 32 kDa (Bam32) and BAFF were decreased. In conclusion, our research demonstrates that virulent strains of PEDV profoundly impact B cell activation, leading to alterations in phenotypic expression and BCR signaling molecules. Furthermore, this dysregulation results in compromised specific antibody secretion and perturbed cytokine production, highlighting the intricate immunological dysfunctions induced by PEDV infection.

Recent advances in the application of Mendelian randomization to chronic kidney disease.

OBJECTIVE: Chronic kidney disease (CKD) is a condition influenced by both genetic and environmental factors and has been a focus of extensive research. Utilizing Mendelian randomization, researchers have begun to untangle the complex causal relationships underlying CKD. This review delves into the advances and challenges in the application of MR in the field of nephrology, shifting from a mere summary of its principles and limitations to a more nuanced exploration of its contributions to our understanding of CKD. METHODS: Key findings from recent studies have been pivotal in reshaping our comprehension of CKD. Notably, evidence indicates that elevated testosterone levels may impair renal function, while higher sex hormone-binding globulin (SHBG) levels appear to be protective, predominantly in men. Surprisingly, variations in plasma glucose and glycated hemoglobin levels seem unaffected by genetically induced changes in the estimated glomerular filtration rate (eGFR), suggesting an independent pathway for renal function impairment. RESULTS: Furthermore, lifestyle factors such as physical activity and socioeconomic status emerge as significant influencers of CKD risk and kidney health. The relationship between sleep duration and CKD is nuanced; short sleep duration is linked to increased risk, while long sleep duration does not exhibit a clear causal effect. Additionally, lifestyle factors, including diet, exercise, and mental wellness activities, play a crucial role in kidney health. New insights also reveal a substantial causal connection between both central and general obesity and CKD onset, while no significant links were found between genetically modified LDL cholesterol or triglyceride levels and kidney function. CONCLUSION: This review not only presents the recent achievements of MR in CKD research but also illuminates the path forwards, underscoring critical unanswered questions and proposing future research directions in this dynamic field.

Short-term outcomes of enhanced recovery after surgery protocol in robotic-assisted McKeown esophagectomy for esophageal cancer: a single-center retrospective cohort study.

Background: This study aimed to evaluate the short-term outcomes of enhanced recovery after surgery (ERAS) protocol in perioperative robotic-assisted McKeown esophagectomy (RAME) among esophageal cancer patients. Methods: For this retrospective study, all patients who had undergone RAME with esophageal cancer using ERAS protocol and conventional management strategy at the surgery center of our hospital from February 2019 to March 2022 were performed for analysis. Results: A total of 211 patients were included. Compared to the conventional group, the ERAS group has shorter median operative time [207 (147.5-267.5) vs. 244 (183-305), P<0.001], time to first flatus (P<0.001), time to out-of-bed activity (P=0.045), and time to liquid diet (P<0.001). In addition, the ERAS group has lower postoperative pain scores (3.62 ± 0.87 vs. 4.54 ± 0.91), shorter duration of analgesia pump [2 (1-3) vs. 3 (2.5-5.5)], shorter postoperative hospital stay [(9 (6-47) vs. 11 (6-79)], shorter postoperative hospital stay within neoadjuvant treated patients [8 (7-43) vs. 13 (8-67], shorter postoperative ICU stay [1 (0-7) vs. 2 (0-15)], and less reoperation rate (7.6% vs. 16.8%). Furthermore, the overall complication rate was significantly lower in the ERAS group (26.1%) than in the conventional group (50.4%). Notably, the ERAS group had lower thoracic fluid drainage volume than the conventional group on postoperative 2-7 days (P<0.05). Conclusions: The application of ERAS protocol in esophageal cancer patients treated with RAME showed advantages of quick postoperative recovery in contrast to the conventional management strategy.

Survival analysis and nomogram for pulmonary sarcomatoid carcinoma: an SEER analysis and external validation.

OBJECTIVE: Uncommon and particularly deadly, pulmonary sarcomatoid carcinoma (PSC) is an aggressive type of lung cancer. This research aimed to create a risk categorisation and nomogram to forecast the overall survival (OS) of patients with PSC. METHODS: To develop the model, 899 patients with PSC were taken from the Surveillance, Epidemiology, and End Results database from the USA. We also used an exterior verification sample of 34 individuals with PSC from Fujian Provincial Hospital in China. The Cox regression hazards model and stepwise regression analysis were done to screen factors in developing a nomogram. The nomogram's ability to discriminate was measured employing the area under a time-dependent receiver operating characteristic curve (AUC), the concordance index (C-index) and the calibration curve. Decision curve analysis (DCA) and integrated discrimination improvement (IDI) were used to evaluate the nomogram to the tumour-node-metastasis categorisation developed by the American Joint Committee on Cancer (AJCC-TNM), eighth edition, and an additional sample confirmed the nomogram's accuracy. We further developed a risk assessment system based on nomogram scores. RESULTS: Six independent variables, age, sex, primary tumour site, pathological group, tumour-node-metastasis (TNM) clinical stage and therapeutic technique, were chosen to form the nomogram's basis. The nomogram indicated good discriminative ability with the C-index (0.763 in the training cohort and 0.746 in the external validation cohort) and time-dependent AUC. Calibration plots demonstrated high congruence between the prediction model and real-world evidence in both the validation and training cohorts. Nomogram outperformed the AJCC-TNM eighth edition classification in both DCA and IDI. Patients were classified into subgroups according to their risk ratings, and significant differences in OS were observed between them (p<0.001). CONCLUSION: We conducted a survival analysis and nomogram for PSC. This developed nomogram holds potential to serve as an efficient tool for clinicians in prognostic modelling.

Role of Lower Esophageal Squamous Cell Carcinoma Margin Location on Abdominal Lymph Node Metastasis Risk.

BACKGROUND: Different sites of esophageal cancer are accompanied by different regional lymph node metastasis (LNM) risks. We aimed to investigate the impact of a lower tumor margin on abdominal LNM risk. METHODS: We enrolled patients who underwent esophagectomy for esophageal squamous carcinoma (ESCC) from 2014 to 2017 in West China Hospital. Overall survival (OS) analysis was performed. We measured the distance between the lower tumor margin and esophagogastric junction (LED) with upper gastrointestinal contrast-enhanced X-ray (UGCXR). Multivariate logistic regression analysis and propensity score matching (PSM) were performed to explore the relationship between LED and the risk of abdominal LNM. Abdominal LNM risk in ESCC was stratified based on the location of the lower tumor margin. A model predicting abdominal LNM risk was constructed and presented with a nomogram. RESULTS: The included patients had an abdominal LNM rate of 48.29%. In multivariate logistic regression analysis, LED was identified as a risk factor for abdominal LNM. Subgroup analysis of middle ESCC showed that patients with an LED less than 10 cm had a significantly higher rate of abdominal LNM than those with an LED greater than 10 cm. The abdominal LNM rate in middle ESCC patients with an LED less than 10 cm was 32.2%, while it was 35.1% in lower ESCC patients whose lower tumor margin did not invade the esophagogastric junction (EGJ), which was comparable after PSM. CONCLUSIONS: LED could help surgeons evaluate the risk of abdominal LNM preoperatively and better guide dissection of abdominal lymph nodes according to risk level.

Perioperative and oncological outcomes of uniportal versus three-port thoracoscopic segmentectomy for lung cancer: a propensity score matching analysis.

Background: With an increasing amount of small nodules being detected, segmentectomy has recently received a great deal of attention. We have previously reported the feasibility and safety of uniportal segmentectomy. This study aims to further compare the perioperative and oncological outcomes of uniportal and three-port thoracoscopic segmentectomy in lung cancer patients. Methods: Patients undergoing thoracoscopic segmentectomy for lung cancer from January 2014 to March 2021 were enrolled. Clinical data were collected from the Western China Lung Cancer Database, a prospectively maintained database at the Department of Thoracic Surgery, West China Hospital. Propensity score matching (PSM) was used to reduce the heterogeneity in baseline characteristics. Perioperative outcomes, 1-, 3-, and 5-year overall survival (OS), and progression-free survival (PFS) were compared. Results: Of the 10,063 lung cancer patients who underwent thoracoscopic lung resection, 2,630 patients receiving segmentectomy were selected (uniportal: 400; three-port: 2,230). After matching, similar results were found between the 2 groups (uniportal: 400; three-port: 1,200) regarding the number of lymph nodes harvested, the length of postoperative hospital stays, chest tube drainage volume, and postoperative complication rate. The mean follow-up duration was 27 months. Uniportal regimen showed similar 1- (100% vs. 99.9%, P=0.36), 3- (100% vs. 90.4%, P=0.20), 5-year OS (97.7% vs. 99.4%, P=0.78), as well as PFS, with the three-port regimen. Conclusions: Uniportal video-assisted thoracoscopic segmentectomy is proven to be safe and feasible, and the perioperative outcomes and oncological results were similar between the uniportal and three-port regimens.

Robot-assisted thymectomy in large anterior mediastinal tumors: A comparative study with video-assisted thymectomy and open surgery.

BACKGROUND: The aim of this study was to evaluate the safety and effectiveness of robot-assisted thymectomy (RAT) in large anterior mediastinal tumors (AMTs) (size ≥6 cm) compared with video-assisted thymectomy (VAT) and open surgery. METHODS: A total of 132 patients with large AMTs who underwent surgical resection from January 2016 to June 2022 were included in this study. A total of 61 patients underwent RAT, 36 patients underwent VAT and 35 patients underwent open surgery. Perioperative outcomes were compared. RESULTS: There were no significant differences in tumor size (p = 0.141), or pathological types (p = 0.903). Compared with the open group, the RAT and VAT groups were associated with a shorter operation time (115.00 vs. 160.00, p = 0.012; 122.50 vs. 160.00, p = 0.071), and less blood loss (50.00 vs. 200.00, p < 0.001; 50.00 vs. 200.00, p < 0.001), respectively. The rate of conversion in the RAT group was similar to that in the VAT group (6.56% vs. 13.89%, p = 0.229). Concomitant resection was less frequently performed in the VAT group than in the RAT and open groups (5.56% vs. 31.15%, p = 0.040; 5.56% vs. 31.43%, p = 0.006). VAT patients had a lower drainage volume (365.00 vs. 700.00 and 910.00 mL, p < 0.001), shorter duration of chest tube (2.00 vs. 3.00 and 4.00, p < 0.001), and shorter hospital stay (5.00 vs. 6.00 and 7.00, p < 0.001) than the RAT and open groups. There was no 30-day mortality in any group. No difference was seen in R0 resection rates (p = 0.846). The postoperative complication rates were similar among the three groups (p = 0.309). Total in-hospital costs (66493.90 vs. 33581.05 and 42876.40, p < 0.001) were significantly higher in the RAT group. CONCLUSIONS: RAT is safe and effective for the resection of large AMTs compared to VAT and open surgery. Vascular resection in RAT is technically feasible. A long-term follow-up is required.

Screening and identification of CNIH4 gene associated with cell proliferation in gastric cancer based on a large-scale CRISPR-Cas9 screening database DepMap.

BACKGROUND: Gastric cancer is a common malignant tumor of digestive tract. The study aimed to identify candidate genes associated with the proliferation and survival of gastric cancer cell through CRISPR-cas9 screening data, which may provide new therapeutic targets for gastric cancer patients. METHODS: Candidate genes related to gastric cancer cell viability by CRISPR-cas9 screening from Depmap and genes differentially expressed between gastric cancer tissues and normal gastric tissues from TCGA were overlapped. WGCNA and KEGG analysis was conducted to performed to identify key pathways and genes. Using CMap, we identified small molecules that might reverse candidate gene expression of gastric cancer. LASSO regression was used to construct a signature to predict overall survival of gastric cancer patients. CCK8 assay was performed to assess the effects of candidate gene on gastric cancer cell proliferation. RESULTS: A total of 710 candidate genes related to gastric cancer cell viability in the DepMap were identified and overlapped with differentially expressed genes in TCGA database, which were enriched in the cell cycle pathway. CMap analysis suggested that molecule drug LY294002 might be a novel choice for gastric cancer treatment. Using Cox univariate analysis and Lasso analysis, we developed a prognostic model including 12 candidate genes, and conducted subgroup analysis and external validation. Moreover, knockdown of the key candidate gene CNIH4 inhibited the proliferation of gastric cancer cells. CONCLUSION: Cell cycle pathway and CNIH4, identified by CRISPR-cas9 screening, were a key pathway and gene that regulate cell viability in gastric cancer. CNIH4 has significant prognostic values and can serve as a new target for gastric cancer patient treatment.

Detection of Porcine Circovirus Type 2a and Pasteurella multocida Capsular Serotype D in Growing Pigs Suffering from Respiratory Disease.

In order to diagnose a respiratory disease in a pig farm, the lungs, spleen, and lymph nodes of three dead pigs were collected for pathogen detection by PCR and isolation on the basis of preliminary clinical diagnosis. The virus isolate was identified by gene sequence analysis and Immunoperoxidase monolayer assay (IPMA). The bacterial isolate was identified by biochemical tests, 16S rDNA sequence analysis, and species- and serotype-specific PCR, and the pathogenicity was analyzed. Porcine circovirus type 2a (PCV2a) genotype from the lungs, spleen, and lymph nodes and Pasteurella (P.) multocida capsular serotypes D from the lungs were found. The PCV2a isolates could specifically bound the anti-PCV2-Cap polyclonal antibody. The 16S rDNA sequence of P. multocida isolates had 99.9% identity with that of the strain from cattle, and the isolate was highly pathogenic to mice. The results showed that the co-infection of PCV2a and P. Multocida capsular serotypes D should be responsible for the disease. The uncommon PCV2a is still prevalent in some pig farms besides the dominant PCV2d genotype. This study could provide important etiological information for effective control and treatment of the disease in pig farms.

Whether the start time of elective lung surgery impacts perioperative outcomes and cost?

Background: Fatigue and the long work hours of surgeons have attracted increasing concern in recent years. We aimed to explore whether starting time was associated with perioperative outcomes and cost for elective lung surgery. Methods: A retrospective study was conducted on elective lung surgery patients at a high surgery-volume center between September 2019 and November 2019. Patients were divided into the "early start group" if the surgery start time was before 4 post meridiem (pm), while the "late start group" was defined as surgery started after 4 pm. Perioperative outcomes and total hospital costs were compared between the two groups. In addition, multivariable logistic regression analysis was performed to identify whether start time was a risk factor for postoperative hospital duration, total hospital cost and length of operation time. Results: A total of 398 patients were finally enrolled for analysis in this study. Of all the cases, 295 patients were divided into the early start group, while 103 patients belonged to the late start group. Baseline characteristics were all comparable between the two groups. Concerning Regarding outcomes, there were no differences in postoperative hospital duration, operation time, complication incidence or and other outcomes, while the total hospital cost tended to be different but still not significantly different without statistical significance (P = 0.07). In multivariable logistic regression analysis, surgery starting late was still not found to be a risk factor for long postoperative hospital duration, high hospital cost and long surgery time. Conclusion: In elective lung surgery, perioperative outcomes and costs were similar between the early- and late-start groups, and it was not necessary to worry about the surgery order for these patients.

Surgical Treatment for Esophageal Leiomyoma: 13 Years of Experience in a High-Volume Tertiary Hospital.

Background: Esophageal leiomyoma is the most common benign tumor in the esophagus. Thoracotomy and thoracoscopy are both elective for esophageal leiomyoma enucleation. This study aimed at presenting surgical experience in our center and exploring more suitable surgical methods for different situations. Methods: We conducted this retrospective study by collecting data from patients who underwent esophageal leiomyoma enucleation through thoracotomy or thoracoscopy from January 2009 to November 2021 at West China Hospital Sichuan University. Results: A total of 34 patients were enrolled for analysis. All patients were diagnosed with a single esophageal leiomyoma. There were 25 men and 9 women. The mean age was 44.41 years (range, 18-72 years), the mean longest diameter was 4.99 cm (range, 1.4-10 cm), and the esophagus was thoroughly circled with leiomyoma in 10 patients, 10 patients underwent thoracotomy to enucleate leiomyoma, while others underwent thoracoscopic enucleation. No perioperative deaths occurred. Between the thoracotomy group and thoracoscopy group, baseline characteristics were comparable except for gastric tube status (p = 0.034). Patients were inclined to undergo the left lateral surgery approach (p = 0.001) and suffered esophagus completely encircled by leiomyoma (p = 0.002). Multivariable logistic regression analysis demonstrated that the left lateral surgery approach (p = 0.014) and esophagus completely encircled by leiomyoma (p = 0.042) were risk factors for thoracotomy of leiomyoma enucleation, while a larger tumor size demonstrated no risk. The median follow-up time was 63.5 months, and no deaths or recurrence occurred during the follow-up period. Conclusion: Thoracotomy enucleation of the leiomyoma was recommended when the esophagus was thoroughly encircled by the leiomyoma and the left lateral surgery approach was needed. However, tumor size demonstrated less value for selecting a surgical approach.

A New Risk Factor for Cervical Anastomotic Leakage-Role of The Relative Gastric Length in the Surgical Treatment of Esophageal Cancer.

BACKGROUND: Blood supply is especially weak near the gastric fundus. Making the anastomosis in this area would increase the risk of anastomotic leakage (AL). In cervical anastomosis, the gastric conduit needs to travel through the thorax. Therefore, the relative length between the stomach and the thorax is an essential factor in deciding if the poorly supplied area could be removed. This study was to explore if a small relative gastric length was a risk of cervical AL. If all other conditions are equal, could intrathoracic anastomosis be a better choice? METHODS: Patients who underwent esophagectomy with a preoperative barium swallow in West China Hospital between 2014 and 2017 were included. The length of the greater curvature and the thorax were obtained from the barium esophagogram. The ratio between the length of the greater curvature and the thorax was the relative gastric length calculated from the greater curvature (RGL-G). RESULTS: A total of 782 patients were enrolled in the final analysis. The cervical AL group had a significantly higher ratio of patients with an RGL-G less than 1.3 (26.7% vs. 8.9%, p = 0.003). The multivariate logistic regression proved that RGL-G less than 1.3 was a risk factor for cervical anastomotic leakage (p = 0.012). Correspondingly, RGL-G less than 1.3 was not a risk factor (6.3% vs. 14.3%, p = 0.289) in the intrathoracic anastomosis group. CONCLUSIONS: RGL-G less than 1.3 was a new risk factor for cervical AL, but it would not be a problem for intrathoracic anastomosis.

Case Report: Not a Mediastinal Mass! a Ruptured Giant Coronary Aneurysm That Occurred in a Young Man.

Introduction: Coronary artery aneurysm (CAA) is a localized coronary artery dilatation that exceeds 1. 5 times the diameter of a standard adjacent segment or the largest coronary vessel. When the expansion is > 2 cm, it is called a "giant" coronary artery aneurysm. Giant coronary artery aneurysm rupture is extremely rare and fatal. Case presentation: We present a rare case of a 27 years old male with a giant coronary artery aneurysm rupture, but no catastrophic events occurred immediately. He was initially misdiagnosed as having a mediastinal mass with CT (computed tomography). The cardiac ultrasound showed no pericardial effusion. But The cardiac CTA (computed tomography angiography) showed a giant coronary aneurysm rupture with hematoma formation. He eventually underwent surgery and was followed up for 2 months without complications. Conclusion: We report this case of a ruptured giant coronary aneurysm because of its infrequent occurrence in coronary artery disease. It is tough to distinguish this disease from a mediastinal tumor, and chest MRI and cardiac CTA are crucial tests. Finally, surgical resection may be the right choice for coronary aneurysm rupture. More cases need to be reported to facilitate the preoperative diagnosis of this rare coronary aneurysm.

Prognostic value of node skip metastasis on esophageal cancer: A systematic review and meta-analysis.

The association between NSM and prognosis of esophageal cancer remains controversial, though several studies have been conducted drawing their own conclusion. Therefore, we firstly carried out this meta-analysis aiming to explore the association. We performed a comprehensive literature search online, including PubMed, Embase and Web of Science. We selected deaths at 5 years and hazard ratio (HR) with 95% (CI) to perform the meta-analysis with Review Manager 5.3, predicting value of clinic-pathological features in NSM also been analyzed. A total of 7 studies were finally enrolled in this study. NSM, defined by either JSED criterion or anatomical compartment criterion, neither showed significant prognostic value on OS of esophageal cancer (P = 0.64), (P = 0.24). Subgroup analysis of JSED criterion, NSM was not a prognostic factor in solitary node metastasis patients (P = 0.39), whereas NSM demonstrated a poor prognostic factor (P = 0.01) for ESCC. Subgroup analysis according to anatomical criterion, NSM was a favorable factor for OS in middle thoracic ESCC (P = 0.003). Pathological N1 status was found to be a risk factor for NSM (P < 0.00001) according to JSED criterion and middle thoracic ESCC was identified as a predictor for NSM (P = 0.0003) according to anatomical compartment criterion. According to JSED criterion, NSM demonstrated poor prognosis on ESCC and N1 status was a risk factor for NSM. Concerning the anatomical compartment criterion, a favorable prognosis of NSM was found in middle thoracic ESCC and NSM was prone to occur in middle thoracic ESCC. CRD42021219333.

Perioperative ctDNA-Based Molecular Residual Disease Detection for Non-Small Cell Lung Cancer: A Prospective Multicenter Cohort Study (LUNGCA-1).

PURPOSE: We assessed whether perioperative circulating tumor DNA (ctDNA) could be a biomarker for early detection of molecular residual disease (MRD) and prediction of postoperative relapse in resected non-small cell lung cancer (NSCLC). EXPERIMENTAL DESIGN: Based on our prospective, multicenter cohort on dynamic monitoring of ctDNA in lung cancer surgery patients (LUNGCA), we enrolled 950 plasma samples obtained at three perioperative time points (before surgery, 3 days and 1 month after surgery) of 330 stage I-III NSCLC patients (LUNGCA-1), as a part of the LUNGCA cohort. Using a customized 769-gene panel, somatic mutations in tumor tissues and plasma samples were identified with next-generation sequencing and utilized for ctDNA-based MRD analysis. RESULTS: Preoperative ctDNA positivity was associated with lower recurrence-free survival (RFS; HR = 4.2; P < 0.001). The presence of MRD (ctDNA positivity at postoperative 3 days and/or 1 month) was a strong predictor for disease relapse (HR = 11.1; P < 0.001). ctDNA-based MRD had a higher relative contribution to RFS prediction than all clinicopathologic variables such as the TNM stage. Furthermore, MRD-positive patients who received adjuvant therapies had improved RFS over those not receiving adjuvant therapy (HR = 0.3; P = 0.008), whereas MRD-negative patients receiving adjuvant therapies had lower RFS than their counterparts without adjuvant therapy (HR = 3.1; P < 0.001). After adjusting for clinicopathologic variables, whether receiving adjuvant therapies remained an independent factor for RFS in the MRD-positive population (P = 0.002) but not in the MRD-negative population (P = 0.283). CONCLUSIONS: Perioperative ctDNA analysis is effective in early detection of MRD and relapse risk stratification of NSCLC, and hence could benefit NSCLC patient management.

Pretreatment-assisted robot intrathoracic layered anastomosis: our exploration in Ivor-Lewis esophagectomy.

BACKGROUND: Minimal invasive Ivor-Lewis esophagectomy (MIIVE) with intrathoracic esophago-gastric anastomosis (EGA) is still under exploration and the preferred technique for intrathoracic anastomosis has not been established. METHODS: We retrospectively reviewed 43 consecutive patients who underwent MIIVE using the series technique called pretreatment-assisted robot intrathoracic layered anastomosis (PRILA), performed by a single surgeon between September 2018 and December 2020. The operative outcomes were analyzed. RESULTS: The mean total operation time had been reduced from 446.38±54.775 minutes (range, 354-552) in the first year to 347.70±60.420 minutes (range, 249-450) later. There were no conversions to thoracotomy. All the patients achieved R0 resection. No patient suffered from anastomotic leakage. There was no 30-day mortality. The median length of postoperative stay was 10.0 days. CONCLUSIONS: PRILA further visualizes and streamlines the process of minimal invasive intrathoracic EGA, thus ensuring the precise anastomosis. It could be considered as a feasible alternative for intrathoracic EGA in MIILE.

Safety profile of preoperative administration of low-molecular-weight heparin on minimally invasive lung cancer surgery: a randomized controlled trial.

BACKGROUND: Venous thromboembolism remains a common but preventable complication for cancerous lung surgical patients. Current guidelines recommend thromboprophylaxis for lung patients at high risk of thrombosis, while a consensus about specific administration time is not reached. This study was designed to investigate the safety profile of preoperative administration of low-molecular-weight-heparin (LMWH) for lung cancer patients. METHODS: From July 2017 to June 2018, patients prepared to undergo lung cancer surgery were randomly divided into the preoperative LMWH-administration group (PRL) for 4000 IU per day and the postoperative LMWH-administration group (POL) with same dosage, all the patients received thromboprophylaxis until discharge. Baseline characteristics including demographics and preoperative coagulation parameters were analyzed, while the endpoints included postoperative coagulation parameters, postoperative drainage data, hematologic data, intraoperative bleeding volume and reoperation rate. RESULTS: A total of 246 patients were collected in this RCT, 34 patients were excluded according to exclusion criterion, 101 patients were assigned to PRL group and 111 patients belonged to POL group for analysis finally. The baseline characteristic and preoperative coagulation parameters were all comparable except the PRL group cost more operation time (p = 0.008) and preoperative administration duration was significantly longer (p < 0.001). The endpoints including postoperative day 1 coagulation parameters, mean and total drainage volume, drainage duration, intraoperative bleeding volume and reoperation rate were all similar between the two groups. Moreover, coagulation parameters for postoperative day 3 between the two groups demonstrated no difference. CONCLUSION: Preoperative administration of low-molecular-weight-heparin demonstrated safety and feasibility for lung cancer patients intended to receive minimally invasive surgery. TRIAL REGISTRATION: ChiCTR2000040547 ( www.chictr.org.cn ), 2020/12/1, retrospectively registered.

From McKeown to Ivor Lewis, the learning curve for thoracic lymphadenectomy over the first 100 robotic esophagectomy cases: a retrospective study.

BACKGROUND: Lymphadenectomy is an essential but challenging part of the surgical treatment for esophageal cancer. However, the previously reported learning curve for robotic esophagectomy primarily focused on only one surgical approach (McKeown or Ivor Lewis). However, both approaches must be mastered by a mature robotic surgical team to deal with different clinical conditions and satisfy patients' needs. This study aimed to show how an experienced esophageal surgical team became proficient in both McKeown and Ivor Lewis robotic esophagectomy. METHODS: A retrospective review of the first 100 cases of robot-assisted minimally invasive esophagectomy (RAMIE) by a single surgical team was performed. The cumulative sum (CUSUM) analysis was used to distinguish the change point during the learning course. A subgroup analysis was performed according to a surgical approach (McKeown or Ivor Lewis) to determine the effect of experience from one surgical approach on learning the other RAMIE technique. RESULTS: According to the tendency of the CUSUM plot, the learning curve was divided into four phases. The subgroup analysis indicated the decline of the CUSUM plot in the 3rd phase originated from the start of the Ivor Lewis approach. The attending surgeon took 23 cases to achieve a significant improvement in the number of harvested thoracic lymph nodes using the McKeown approach. Regardless of the acquired experience of McKeown RAMIE, it took another 18 cases for the surgical team to achieve significant improvement in harvesting thoracic lymph nodes using the Ivor Lewis approach. CONCLUSIONS: Twenty-three cases were needed for an experienced surgical team to improve thoracic lymphadenectomy results using McKeown RAMIE. There was another learning phase during the transition from McKeown to Ivor Lewis esophagectomy. Importantly, the acquired experience from performing McKeown RAMIE could shorten how long it takes to learn Ivor Lewis RAMIE.