Establishment and verification of novel TNM staging system for lung mucinous adenocarcinoma.

BACKGROUND: Lung adenocarcinoma is a high-mortality rate cancer. Within this category, Lung mucinous adenocarcinoma (LMAC) is a rare and distinct subtype of lung adenocarcinoma necessitating further investigation. The study was launched to compare the difference of survival features between LMAC and lung non-mucinous adenocarcinoma (LNMAC) and to investigate the significance and demand for developing a new staging system tailored to LMAC. METHODS: This retrospective study assessed the suitableness of the current staging system for LMAC. It compared the overall survival (OS) between LMAC and LNMAC from 2004 to 2020 (LNMAC: 160,387; LMAC: 6,341) and instituted a novel classification framework for LMAC based on US population. Verification group consisting of patients from two Chinese medical centers from 2010 to 2018 (n = 392) was set to ascertain the applicability of this novel system. The primary endpoint was OS. To minimize the bias, propensity score match (PSM) was employed. Survival analysis and Log-rank test were executed to explore the survival features of LMAC. RESULTS: The results indicated that the existed staging system was not suitable for LMAC. Patients diagnosed with LMAC exhibited a superior OS compared to those with LNMAC in stage IA2 (P < 0.0001), IA3 (P < 0.0001), IB (P = 0.0062), IIA (P = 0.0090), IIB (P = 0.0005). In contrast, a worse OS in stage IVA (P = 0.0103) was found in LMAC patients. The novel classification system proposed for LMAC proved to be highly applicable and demonstrated substantial efficacy, as confirmed by the verification group. CONCLUSION: The newly established classification system was more effective for LMAC, but it necessitates large-scale verification to confirm its applicability and reliability.

Comparison of the clinical outcomes after esophagectomy between intrathoracic anastomosis and cervical anastomosis: a systematic review and meta-analysis.

OBJECTIVES: Esophageal cancer is a high-mortality disease. Esophagectomy is the most effective method to treat esophageal cancer, accompanied with a high incidence of post-operation complications. The anastomosis has a close connection to many severe post-operation complications. However, it remains controversial about the choice of intrathoracic anastomosis (IA) or cervical anastomosis (CA). The study was conducted to compare the clinical outcomes between the two approaches. METHODS: We searched databases for both randomized controlled trials (RCTs) and cohort studies comparing post-operation outcomes between IA and CA. Primary outcomes were the incidences of anastomotic leakage and mortality. Secondary outcomes were the incidences of anastomotic stenosis, pneumonia and re-operation. RESULTS: Twenty studies with a total of 7,479 patients (CA group: n = 3,183; IA group: n = 4296) were included. The results indicated that CA group had a higher incidence of anastomotic leakage than IA group (odds ratio [OR] = 2.05, 95% confidence intervals [CI] = 1.61-2.60, I2 = 53.31%, P < 0.01). Subgroup analyses showed that CA group had higher incidences of type I (OR = 2.19, 95%CI = 1.05-4.57, I2 = 0.00%, P = 0.04) and type II (OR = 2.75, 95%CI = 1.95-3.88, I2 = 1.80%, P < 0.01) anastomotic leakage than IA group. No difference was found in type III anastomotic leakage (OR = 1.23, 95%CI = 0.82-1.86, I2 = 20.92%, P = 0.31). The 90-day mortality (OR = 1.66, 95%CI = 1.11-2.47, I2 = 0.0%, P = 0.01) in IA group were lower than that in CA group. No difference was found in in-hospital mortality (OR = 1.31, 95%CI = 0.91-1.88, I2 = 0.00%, P = 0.15) and 30-day mortality (OR = 1.08, 95%CI = 0.69-1.70, I2 = 0.00%, P = 0.74). CONCLUSIONS: IA might be a better anastomotic approach than CA, with a lower incidence of anastomosis leakage and no increase in short-term mortality. Significant heterogeneity and publication bias might limit the reliability of the results. More high-quality studies are needed to verify and update our findings.

Long-term outcomes of robotic-assisted versus thoraco-laparoscopic McKeown esophagectomy for esophageal cancer: a propensity score-matched study.

The long-term outcomes of robotic-assisted McKeown esophagectomy (RAME) compared to thoraco-laparoscopic McKeown esophagectomy (TLME) for the patients with esophageal squamous cell carcinoma (ESCC) remain unclear. The aim of this study was to compare the number of dissected lymph nodes and long-term survival between RAME and TLME using a propensity score-matched (PSM) analysis. A total of 721 patients undergoing minimally invasive McKeown esophagectomy at our department from February 2015 to October 2019 were analyzed, including 310 patients in RAME group and 411 in TLME group. The exact numbers of lymph nodes including those among thoracic and abdominal categories as well as those along the recurrent laryngeal nerve (RLN) were all recorded. PSM analysis was applied to generate matched pairs for further comparison. All patients with R0 resection were followed with a strict follow-up period which range from 1 to 56 months. The effect of lymphadenectomy was compared between all patients in unmatched and matched groups. Long-term outcomes consisting of overall survival (OS), disease-free survival (DFS) and recurrence rate (including regional recurrence rate, systemic recurrence rate and mediastinal lymph nodes recurrence rate) were compared in R0 resection patients. Finally, 292 patients were identified for each cohort after PSM. RAME was found to yield significantly more left RLN lymph nodes (mean: 2.27 ± 0.90 vs. 2.09 ± 0.79; P = 0.011) and more thoracic lymph nodes (mean: 12.60 ± 4.22 vs. 11.83 ± 3.12, P = 0.012) compared with TLME after PSM analysis. There was no significant difference in the OS and DFS between the RAME and TLME group. Besides, total recurrences were recognized in 33 (11.7%) patients in the RAME group and 36 (12.9%) in the TLME group (P = 0.676). The mediastinal lymph nodes recurrence rate in the RAME group was tended to be lower than that in the TLME group (2.5% vs. 5.4%, P = 0.079). Therefore, RAME might be an alternative approach for the treatment of ESCC with more lymph nodes dissected and similar long-term survival outcomes compared to TLME.

Does robot-assisted minimally invasive oesophagectomy have superiority over thoraco-laparoscopic minimally invasive oesophagectomy in lymph node dissection?

Although robotic techniques have been used for oesophagectomy for many years, whether robot-assisted minimally invasive oesophagectomy (RAMIE) can actually improve outcomes and surpass thoraco-laparoscopic minimally invasive oesophagectomy (MIE) in the success rate of lymph node dissection remains to be empirically demonstrated. Therefore, we performed this systematic review and meta-analysis of case-control studies to systematically compare the effect of lymph node dissection and the incidence of vocal cord palsy between RAMIE and MIE. The PubMed, EMBASE, and Web of Science databases were systematically searched up to December 1, 2019, for case-control studies that compared RAMIE with MIE. Thirteen articles were included, with a total of 1,749 patients with esophageal cancer, including 866 patients in the RAMIE group and 883 patients in the MIE group. RAMIE yielded significantly larger numbers of total dissected lymph nodes (WMD = 1.985; 95% CI, 0.448-3.523; P = 0.011) and abdominal lymph nodes (WMD = 1.686; 95% CI, 0.420-2.951; P = 0.009) as well as lymph nodes along RLN (WMD = 0.729; 95% CI, 0.348-1.109; P < 0.001) than MIE. Additionally, RAMIE could significantly decrease estimated blood loss (WMD = -11.208; 95% CI, -19.358 to -3.058; P = 0.007) and the incidence of vocal cord palsy (OR = 0.624; 95% CI, 0.411-0.947; P = 0.027) compared to MIE. Compared with MIE, RAMIE resulted in a higher total lymph node yield and a higher lymph node yield in the abdomen and along RLN, along with reduced blood loss during surgery and the incidence of vocal cord palsy. Therefore, RAMIE could be considered to be a standard treatment, with less blood loss, lower incidence of vocal cord palsy, and more radical lymph node dissection, exhibiting superiority over MIE.

Long non-coding RNA linc00665 interacts with YB-1 and promotes angiogenesis in lung adenocarcinoma.

Angiogenesis is a core hallmark of advanced cancers, especially in lung adenocarcinoma (LUAD). However, the underlying functions and mechanisms of lncRNAs in tumor angiogenesis remain largely unknown. Here we found that linc00665 depletion could markedly depressed proliferation and capillary tube formation of HUVECs in vitro. Mechanistically, linc00665 directly interacted with YB-1 protein, enhanced its stability through inhibiting ubiquitination-dependent proteolysis and stimulated its nuclear translocation in LUAD cells. The accumulated nuclear YB-1 activated expression of ANGPT4, ANGPTL3 and VEGFA by binding to their promoters, contributing to tumor-related angiogenesis in vitro and in vivo. Collectively, we conclude that linc00665 induces tumor-related angiogenesis in LUAD by directly interacting with YB-1 and activating YB-1-ANGPT4/ANGPTL3/VEGFA axis, which provides promising anti-angiogenic targets for cancer therapy.

High expression of C-X-C chemokine receptor 4 and Notch1 is predictive of lymphovascular invasion and poor prognosis in lung adenocarcinoma.

C-X-C chemokine receptor 4 and Notch1 have been shown to play oncogenic role individually. This study aimed to determine the combinatorial role of C-X-C chemokine receptor 4 and Notch1 in lung adenocarcinoma. Expression of C-X-C chemokine receptor 4 and Notch1 was detected in resected tumor samples from 185 patients with lung adenocarcinoma at stage I-IIIa by immunohistochemistry. Correlations of their immunoscores with clinicopathological characteristics and disease-specific survival were retrospectively investigated. A three-dimensional capillary-like sprouting model was established to assess the effects of C-X-C chemokine receptor 4 and Notch1 on angiogenesis in vitro. The results revealed that expression of C-X-C chemokine receptor 4 and Notch1 was elevated in lung adenocarcinoma tissues. The high co-expression of C-X-C chemokine receptor 4 and Notch1 was significantly correlated with tumor size, tumor status, nodal status, tumor stage, and lymphovascular invasion, as well as decreased disease-specific survival. Multivariate analysis showed that lymphovascular invasion (hazard ratio: 0.205, 95% confidence interval: 0.086-0.491, p < 0.0001) and co-expression of C-X-C chemokine receptor 4 and Notch1 (hazard ratio: 0.293, 95% confidence interval: 0.168-0.510, p < 0.0001) were independent indicators of poor prognosis in lung adenocarcinoma. Furthermore, Notch1 enhanced the effects of C-X-C chemokine receptor 4 to promote angiogenesis by regulating Flt1 and Flt4 in vitro. In conclusion, co-expression of C-X-C chemokine receptor 4 and Notch1 is associated with tumor progression and lymphovascular invasion and is an independent indicator of poor survival in lung adenocarcinoma. In lung adenocarcinoma patients with high C-X-C chemokine receptor 4 and Notch1 expression, simultaneous inhibition of both factors might be an effective treatment strategy.

Protective effect of melatonin on the development of abdominal aortic aneurysm in a rat model.

BACKGROUND: Oxidative injury, inflammation, and apoptosis are involved in the progression of abdominal aortic aneurysm (AAA). Melatonin (MLT) has been reported with an effective antioxidant activity. The objective of the present study was to investigate whether MLT could suppress the development of AAA. METHODS: The AAA model was introduced by intraluminal perfusion of elastase in rats. All rats were divided into three groups as follows: (1) sham; (2) AAA + vehicle; and (3) AAA + MLT. Daily administration of MLT (10 mg/kg/d) or vehicle started 3 d before the perfusion and continued for 28 d after perfusion. An ultrasound system was applied to measure the dilation of the aorta. Histologic assays were performed to evaluate the structure, morphology, and apoptotic cells of the aortas; biochemical assays to determine the levels of proteins and lipid peroxide, activities of superoxide dismutase and NADPH oxidases, and cell viability; dihydroethidium fluorescence staining and flow cytometry to detect the presence of reactive oxygen species, and/or cell apoptosis; and electron microscopy to observe the ultrastructure of mitochondria. Cell lines A7R5 and RAW 264.7 were used for in vitro experiments. RESULTS: MLT treatment inhibited dilation of the aorta very likely through its antioxidant property; significantly reduced the levels of lipid peroxide, activities of NADPH oxidases, and content of reactive oxygen species; remarkably inhibited NF-κB signaling pathway and activities of matrix metalloproteinases triggered by elastase perfusion. As a result, the mitochondrion-dependent apoptosis was suppressed, cellular energy (ATP) supply was recovered, and mitochondrial morphology remained intact. CONCLUSIONS: Our results demonstrate the beneficial effects of MLT on inhibition of AAA formation, suggesting that MLT could be a potential agent for prevention of the development of human AAA.

In vitro modeling of endothelial interaction with macrophages and pericytes demonstrates Notch signaling function in the vascular microenvironment.

Angiogenesis is regulated by complex interactions between endothelial cells and support cells of the vascular microenvironment, such as tissue myeloid cells and vascular mural cells. Multicellular interactions during angiogenesis are difficult to study in animals and challenging in a reductive setting. We incorporated stromal cells into an established bead-based capillary sprouting assay to develop assays that faithfully reproduce major steps of vessel sprouting and maturation. We observed that macrophages enhance angiogenesis, increasing the number and length of endothelial sprouts, a property we have dubbed "angiotrophism." We found that polarizing macrophages toward a pro-inflammatory profile further increased their angiotrophic stimulation of vessel sprouting, and this increase was dependent on macrophage Notch signaling. To study endothelial/pericyte interactions, we added vascular pericytes directly to the bead-bound endothelial monolayer. These pericytes formed close associations with the endothelial sprouts, causing increased sprout number and vessel caliber. We found that Jagged1 expression and Notch signaling are essential for the growth of both endothelial cells and pericytes and may function in their interaction. We observed that combining endothelial cells with both macrophages and pericytes in the same sprouting assay has multiplicative effects on sprouting. These results significantly improve bead-capillary sprouting assays and provide an enhanced method for modeling interactions between the endothelium and the vascular microenvironment. Achieving this in a reductive in vitro setting represents a significant step toward a better understanding of the cellular elements that contribute to the formation of mature vasculature.

Effect of early enteral nutrition on short-term outcomes and survival in patients in the cardiothoracic intensive care unit: An inverse probability weighted retrospective study.

OBJECTIVES: The merits of early enteral nutrition (EEN) in patients in the cardiothoracic intensive care unit (CTICU) remain unclear. This retrospective study aimed to address this issue. METHODS: We analyzed data from the MIMIC IV v2.0 database, including patients with a CTICU stay of ≥4 d. Patients were divided into early and delayed enteral nutrition (EN) groups. Differences in baseline data were corrected using an inverse probability weighting (IPW) approach. Generalized linear models (GLMs) were used to compare trends over time between groups, and survival effects were evaluated with weighted logistic and Cox regression, supplemented by weighted Kaplan-Meier curves. Subgroup analysis facilitated the exploration of potential interactions. RESULTS: The study included 720 CTICU patients. Following IPW, all baseline variables were balanced. EEN led to shorter hospital and CTICU stays, lower incidence of respiratory and blood infections, and reduced total insulin usage in the first week of CTICU admission, albeit with an increased total gastric residual volume. Mortality risk between the groups did not significantly differ at 28 d or at 1 y. Excessive early energy and protein intake elevated the risk of 28-d mortality, but the relationship may not be linear. Overweight patients or those with fewer comorbidities had a higher mortality risk with EEN. CONCLUSIONS: EEN may improve short-term outcomes in CTICU patients without a clear survival benefit. Early high caloric and protein intake could lead to adverse outcomes, suggesting a careful evaluation for initiating EN in specific patients.

Effect of nutrition-based prehabilitation on the postoperative outcomes of patients with esophagogastric cancer undergoing surgery: A systematic review and meta-analysis.

BACKGROUND: Meta-analyses have primarily focused on the effects of exercise-based prehabilitation on postoperative outcomes and ignored the role of nutritional intervention. In this study, we filled this gap by investigating the effect of nutrition-based prehabilitation on the postoperative outcomes of patients who underwent esophagectomy and gastrectomy. METHODS: Five electronic databases, namely, PubMed, the Web of Science, Embase, Cochrane Library, and CINAHL, were searched. Adults diagnosed with esophagogastric cancer who were scheduled to undergo surgery and had undergone uni- or multimodal prehabilitation, with at least a week of mandatory nutritional intervention, were included. Forest plots were used to extract and visualize the data from the included studies. The occurrence of any postoperative complication was considered the primary endpoint. RESULTS: Eight studies met the eligibility criteria, with five randomized controlled trials (RCTs) and three cohort studies. In total, 661 patients were included. Any prehabilitation, that is, unimodal (only nutrition) and multimodal prehabilitation, collectively decreased the risk of any postoperative complication by 23% (95% confidence interval [CI] = 0.66-0.90). A similar effect was exclusively observed for multimodal prehabilitation (risk ratio [RR] = 0.78, 95% CI = 0.66-0.93); however, it was not significant for unimodal prehabilitation. Any prehabilitation significantly decreased the length of hospital stay (LOS) (weighted mean difference = -0.77, 95% CI = -1.46 to -0.09). CONCLUSIONS: Nutrition-based prehabilitation, particularly multimodal prehabilitation, confers protective effects against postoperative complications after esophagectomy and gastrectomy. Our findings suggest that prehabilitation slightly decreases LOS; however, the finding is not clinically significant. Therefore, additional rigorous RCTs are warranted for further substantiation.

Safety and feasibility of a novel chest tube placement in uniportal video-assisted thoracoscopic surgery for non-small cell lung cancer.

BACKGROUND: The type and placement of chest tube for patients undergoing uniportal video-assisted thoracoscopic lobectomy remains controversial. The aim of this study was to assess the efficacy and safety of a novel technique in which a pigtail catheter was used alone as the chest tube and placed near the incision for chest drainage after uniportal video-assisted thoracoscopic lobectomy and extended lymphadenectomy. METHODS: A total of 217 patients undergoing uniportal video-assisted thoracoscopic lobectomy were retrospectively reviewed and divided into two groups. In group A, a 12-Fr pigtail catheter with several side ports was placed next to the uniportal wound. In group B, a conventional 20-Fr chest tube was placed through the uniportal wound itself. Postoperative complications related to chest tube placement and patients' subjective satisfaction were compared between the two groups. Postoperative pain management effect and other clinical outcomes such as duration of chest drainage and postoperative stay were also compared. RESULTS: There were 112 patients in group A and 105 patients in group B. A significantly lower incidence of wound complications was found in group A postoperatively (p = 0.034). The pain score on coughing in group A was significantly lower than that in group B on postoperative day two (POD2) (p = 0.021). There was no significant difference of other clinical outcomes such as duration of chest drainage and postoperative stay as well as major complications between the two groups. CONCLUSION: Placing a 12-Fr pigtail catheter alone next to the uniportal wound for chest drainage might be effective and safe after uniportal video-assisted thoracoscopic lobectomy and extended lymphadenectomy.

Prognostic significance of tumor regression grade in esophageal squamous cell carcinoma after neoadjuvant chemoradiation.

Backgrounds: Trimodal therapy (neoadjuvant chemoradiotherapy followed by esophagectomy) for locally advanced esophageal squamous cell carcinoma (ESCC) is associated with a significant survival benefit. Modified Ryan score is an effective tool to evaluated the tumor regression grade (TRG) after neoadjuvant therapy. The aim of this study was to evaluate the prognostic value of TRG for overall survival (OS) and disease-free survival (DFS) in ESCC patients undergoing neoadjuvant chemoradiation. Methods: The study retrospectively reviewed 523 ESCC patients who underwent neoadjuvant chemoradiotherapy and radical esophagectomy at Jinling Hospital from January 2014 to July 2020. Kaplan-Meier curves with log-rank test and Cox regression model were used to evaluate the prognostic factor of TRG based on modified Ryan scoring system on OS and DFS. Results: After application of inclusion and exclusion criteria, 494 patients with ESCC following neoadjuvant chemoradiotherapy and radical esophagectomy were available for analysis. The TRG scores are significantly associated with smoke history (p = 0.02), lymphovascular invasion (LVI) and/or peripheral nerve invasion (PNI) (p < 0.01), and postoperative adjuvant therapy (p < 0.01). Meanwhile, tumor characteristics including tumor length (p < 0.01) and tumor differentiation grade (p < 0.01) are also significantly associated with TRG score. The results of multivariable Cox regression modal showed that TRG is not an independently prognostic factor for OS (p = 0.922) or DFS (p = 0.526) but tumor length is an independently prognostic factor for DFS (p = 0.046). Conclusions: This study evaluated the prognostic value of modified Ryan scoring system for ESCC after trimodal therapy and concluded that modified Ryan scoring system can predict survival and recurrence rates but is not an independently prognostic factor for OS and DFS.

Home enteral nutrition for patients with esophageal cancer undergoing esophagectomy: A systematic review and meta-analysis.

Introduction: Home enteral nutrition (HEN) is a relatively new nutritional intervention that provides patients with EN support at home through jejunostomy or nasogastric feeding tubes. We conducted this systematic review and meta-analysis to explore the safety and effect of HEN compared with normal oral diet (NOD) in postoperative patients with esophageal cancer (EC). Methods: EMBASE, Medline, Web of Science, and the Cochrane Library were used to search articles in English-language journals. The intervention effect was expressed using risk ratios (RRs) for dichotomous outcomes and mean differences (MDs) for continuous outcome measures, with 95% confidence intervals (95% CIs). The chi-square test and I-square test were used to test heterogeneity among studies. Results: Four studies were eventually included in this meta-analysis. Compared with NOD, HEN has a favorable impact on postoperative body mass index (BMI) (weighted mean difference [WMD] = 0.70, 95% CI: 0.09-1.30, P = 0.02), lean body mass (LBM) (WMD = 0.76, 95% CI: 0.04-1.48, P = 0.04), and appendicular skeletal muscle mass index (ASMI) (WMD = 0.30, 95% CI: 0.02-0.58, P = 0.03). Physical function (WMD = 9.26, 95% CI: 8.00-10.53, P < 0.001), role function (WMD = 9.96, 95% CI: 8.11-11.82, P < 0.001), and social function (WMD = 8.51, 95% CI: 3.48-13.54, P = 0.001) of the HEN group were better than those of the NOD group at 3 months, and HEN could reduce the fatigue of patients (WMD = -12.73, 95% CI: -14.8 to -10.66, P < 0.001) and the incidence of postoperative pneumonia (RR = 0.53, 95% CI: 0.34-0.81, P = 0.004). There was no significant difference in albumin between HEN and NOD groups (WMD = 0.05, 95% CI: -0.03 to 0.13, P = 0.20). Conclusion: HEN improved nutritional status and quality of life (QOL) in postoperative patients with EC and reduced fatigue and the incidence of postoperative pneumonia. All in all, the results of our meta-analysis support the use of HEN after esophagectomy.

The Prognostic Value of Postoperative Radiotherapy for Thymoma and Thymic Carcinoma: A Propensity-Matched Study Based on SEER Database.

(1) Objectives: The effect of postoperative radiotherapy (PORT) for thymoma and thymic carcinoma remains controversial. This study aimed to investigate the prognostic value of PORT for thymoma and thymic carcinoma in a population-based registry. (2) Methods: This retrospective study used the Surveillance, Epidemiology, and End Results (SEER) database to identify patients diagnosed with thymoma and thymic carcinoma between 2010 and 2019. Propensity score matching was performed to adjust statistical influences between the PORT and non-PORT groups. (3) Results: A total of 2558 patients with thymoma (n = 2138) or thymic carcinoma (n = 420) were included. In the multivariate analysis, PORT was an independent prognostic factor for OS (overall survival; p < 0.001) and CSS (cancer-specific survival; p = 0.001) in thymoma and an independent prognostic factor for OS in thymic carcinoma (p = 0.018). Subgroup analyses revealed that PORT was beneficial to OS and CSS in patients with Masaoka-Koga stage IIB-IV thymoma (OS: IIB, p < 0.001; III-IV, p = 0.005; CSS: IIB, p = 0.015; III-IV, p = 0.002) and stage IIB thymic carcinoma (OS: p = 0.012; CSS: p = 0.029). (4) Conclusion: This propensity-matched analysis identified the prognostic value of PORT in thymoma and thymic carcinoma based on the SEER database. For patients with stage IIB-IV thymoma and stage IIB thymic carcinoma, PORT was associated with improved OS and CSS. A more positive attitude towards the use of PORT for nonlocalized thymoma and thymic carcinoma may be appropriate.

Efficacy of immunonutritional supplement after neoadjuvant chemotherapy in patients with esophageal cancer.

BACKGROUND: In recent years, preoperative nutrition has received great attention, especially for patients who received surgical reconstruction of the digestive tract such as esophagectomy. Preoperative nutrition therapy was reported to accelerate the patient's postoperative recovery. In addition, immune suppression, nausea, and vomiting may lead to poor immune and nutritional status of patients with esophageal cancer who underwent neoadjuvant chemotherapy (NAC), which is not conducive to surgery. Therefore, preoperative nutritional treatment is necessary for patients with esophageal cancer who underwent NAC. METHOD: Patients with esophageal cancer who received NAC at Nanjing Jinling Hospital from January 2018 to September 2020 were retrospectively identified. Patients were divided into enteral immunonutrition (EIN) group (those who received a conventional diet and immunonutrition supplement, Peptisorb, Nutricia, 500 mL/day * 7 via oral intake), and control group (those who only received a conventional diet were divided into). The primary outcomes were immune and nutritional indicators changes, including immunoglobulin M (IgM), immunoglobulin A (IgA), immunoglobulin G (IgG), and albumin (ALB), which were measured at preoperative day (PRD) 7, PRD-1, postoperative day (POD) 1 and POD-7. The secondary outcomes were postoperative complications, adverse reactions, and length of hospital stay. RESULTS: A total of 124 eligible patients were included in the study, with 21 patients in EIN group. After 1:2 matching, significant difference in baseline characteristics between the two groups was not observed (EIN: n = 21, Control group: n = 42). Compared with the control group, the IgA is significantly increased in the EIN group at POD-7 (p = 0.017). However, we observed that the IgM level in the control group was significantly higher than those in the EIN group at POD-7 (p = 0.007). The incidence of pneumonia and total complications in the EIN group were significantly lower than those in control group (p = 0.024, p = 0.028, respectively). There is no significant difference in ALB and adverse reactions between two groups (p = 0.303, p = 0.108, respectively). CONCLUSION: Immunonutritional supplement after NAC is an effective strategy to improve the postoperative immune status of esophageal cancer patients and could reduce the incidence of infectious complication. More well-designed prospective studies are needed to verify and update our finding.

A RASSF8-AS1 based exosomal lncRNAs panel used for diagnostic and prognostic biomarkers for esophageal squamous cell carcinoma.

BACKGROUND: Exosomal long non-coding RNA (lncRNA) has been shown to be potential biomarker for cancer diagnosis and follow up. However, little is known about its application in esophageal squamous cell carcinoma (ESCC) detection. Here, we sought to develop a novel diagnostic model based on serum exosomal lncRNAs to improve ESCC screening efficiency. METHODS: A multiphase, case-control study was conducted among 140 ESCC patients and 140 healthy controls. Microarray screening was performed to acquire differentially expressed exosomal lncRNAs in the discovery phase. The diagnostic model Index I was constructed based on a panel of three lncRNAs using logistic regression in the training phase, and were confirmed in a subsequent validation phase. A receiver operating characteristic (ROC) curve was generated to calculate the diagnostic value. The effects of the selected lncRNAs level on ESCC mortality were evaluated using a Cox hazard regression model and Kaplan-Meier curve analysis, and the expression level with clinicopathological features was also calculated. Finally, we explored the oncogenic potential of candidate lncRNA RASSF8-AS1 in vitro and by target mRNA sequencing. RESULTS: Index I was able to discriminate ESCC patients from healthy controls, and showed superiority to classic tumor biomarkers. Moreover, serum levels of the exosomal lncRNAs correlated with clinicopathological features and prognosis. The in vitro assays showed that RASSF8-AS1 played an oncogenic role in ESCC. Target mRNA scanning results suggested involvement of RASSF8-AS1 in tumor immunity and metabolism. CONCLUSION: The newly identified serum exosomal lncRNAs could be used as new biomarkers for ESCC, and showed oncogenic potential in ESCC.

Safety analysis of early oral feeding after esophagectomy in patients complicated with diabetes.

OBJECTIVE: To evaluate the safety of early oral feeding in patients with type II diabetes after radical resection of esophageal carcinoma. METHODS: The clinical data of 121 patients with type II diabetes who underwent radical resection of esophageal carcinoma in the department of cardiothoracic surgery of Jinling Hospital from January 2016 to December 2018 were retrospectively analyzed. According to the median time (7 days) of the first oral feeding after surgery, the patients were divided into early oral feeding group (EOF, feeding within 7 days after surgery, 67 cases) and late oral feeding group (LOF, feeding after 7 days, 54 cases). Postoperative blood glucose level, incidence of complications, nutritional and immune indexes, inflammatory indexes, normalized T12-SMA (the postoperative/preoperative ratio of vertical spinal muscle cross-sectional area at the 12th thoracic vertebra level) and QLQ-C30 (Quality Of Life Questionnaire) scores were recorded and compared in the two groups. RESULTS: There was no statistical difference in preoperative nutritional index and postoperative complication rates between the EOF and LOF group (p > 0.05). The postoperative nutritional index (ALB, PA, TRF, Hb) and immune index (IgA, IgG, IgM) of the EOF group were higher than those of the LOF group (p < 0.05), and the inflammatory indicators (CRP, IL-6) of the EOF group were significantly lower than those of the LOF group (p < 0.05). Moreover, postoperative T12-SMA variation and QLQ-C30 scores of the EOF group were higher than those in LOF group (p < 0.05). CONCLUSIONS: Early oral feeding is safe and feasible for patients with type II diabetes after radical resection of esophageal cancer, and it can improve short-term nutritional status and postoperative life quality of the patients.

Development and validation of a new clinical staging system to predict survival for esophageal squamous cell carcinoma patients: Application of the nomogram.

INTRODUCTION: Survival of patients with the same clinical stage varies widely and effective tools to evaluate the prognosis utilizing clinical staging information is lacking. This study aimed to develop a clinical nomogram for predicting survival of patients with Esophageal Squamous Cell Carcinoma (ESCC). MATERIALS AND METHODS: On the basis of data extracted from the SEER database (training cohort, n = 3375), we identified and integrated significant prognostic factors for nomogram development and internal validation. The model was then subjected to external validation with a separate dataset obtained from Jinling Hospital of Nanjing Medical University (validation cohort, n = 1187). The predictive accuracy and discriminative ability of the nomogram were determined by concordance index (C-index), Akaike information criterion (AIC) and calibration curves. And risk group stratification was performed basing on the nomogram scores. RESULTS: On multivariable analysis of the training cohort, seven independent prognostic factors were identified and included into the nomogram. Calibration curves presented good consistency between the nomogram prediction and actual observation for 1-, 3-, and 5-year OS. The AIC value of the nomogram was lower than that of the 8th edition American Joint Committee on Cancer TNM (AJCC) staging system, whereas the C-index of the nomogram was significantly higher than that of the AJCC staging system. The risk groups stratified by CART allowed significant distinction between survival curves within respective clinical TNM categories. CONCLUSIONS: The risk stratification system presented better discriminative ability for survival prediction than current clinical staging system and might help clinicians in decision making.

The ratio of gastric tube length to thorax length: a vital factor affecting leak after esophageal cervical anastomosis.

BACKGROUND: Esophagogastric anastomotic leak (AL) is a severe complication following esophageal resection. This study aims to explore preliminarily whether the ratio of the gastric conduit length to the thorax length can be regarded as a potential prognostic variable for AL, and if so, a cut-off value can be found to divide the patients into distinct risk groups. METHODS: We retrospectively reviewed the clinical data of 273 patients who underwent esophagectomy. The gastric conduit length, the thorax length, and other covariates were collected. Logistic regression was first conducted to probe the rationality of the ratio as a risk indicator of AL. Then the dichotomizing analysis was applied to find the optimal cut-off value. RESULTS: The incidence of AL was 12.5% (34/273). The coefficient of the ratio in the logistic regression equation was -7.901 with P<0.001, which indicated that the larger the ratio, the smaller the risk of AL. Further smoothed scatter plots revealed that a potential step function of the ratio of AL incidence exists, of which the steep part ranges from 1.74 to 1.90. Results of the accurate cut-off value search through a minimum P value approach give the optimal dichotomization point of 1.79. CONCLUSIONS: The ratio of the gastric conduit length to the thorax length can reflect the tension in the anastomosis. The research proposes that surgeons can control the length of the gastric conduit during reconstruction to reduce the tension in the anastomosis and thus lead to a decrease in the incidence of AL.

Comparison of short-term clinical outcomes between robot-assisted minimally invasive esophagectomy and video-assisted minimally invasive esophagectomy: a systematic review and meta-analysis.

BACKGROUND: Though robot-assisted minimally invasive esophagectomy (RAMIE) is demonstrated to offer a better visualization and provide a fine dissection of the mediastinal structures to facilitate the complex thoracoscopic operation, the superiorities of RAMIE over MIE have not been well verified. The aim of this study was to explore the actual superiorities through comparing short-term results of RAMIE with that of MIE. METHODS: PubMed, EMBASE and web of science databases were systematically searched up to September 1, 2020 for case-controlled studies that compared RAMIE with TLMIE. RESULTS: Fourteen studies were identified, with a total of 2,887 patients diagnosed with esophageal cancer, including 1,435 patients subjected to RAMIE group and 1,452 patients subjected to MIE group. The operative time in RAMIE was still significantly longer than that in MIE group (OR =0.785; 95% CI, 0.618-0.952; P<0.001). The incidence of pneumonia was significantly lower in RAMIE group compared with MIE group (OR =0.677; 95% CI, 0.468-0.979; P=0.038). CONCLUSIONS: RAMIE has the superiorities over MIE in short-term outcomes in terms of pneumonia and vocal cord palsy. Therefore, RAMIE could be considered as a standard treatment for patients with esophageal cancer.