Zedoary turmeric oil injection ameliorates lung inflammation via platelet factor 4 and regulates gut microbiota disorder in respiratory syncytial virus-infected young mice.

BACKGROUND: Respiratory syncytial virus (RSV)-induced lung inflammation is one of the main causes of hospitalization and easily causes disruption of intestinal homeostasis in infants, thereby resulting in a negative impact on their development. However, the current clinical drugs are not satisfactory. Zedoary turmeric oil injection (ZTOI), a patented traditional Chinese medicine (TCM), has been used for clinical management of inflammatory diseases. However, its in vivo efficacy against RSV-induced lung inflammation and the underlying mechanism remain unclear. PURPOSE: The present study was designed to confirm the in vivo efficacy of ZTOI against lung inflammation and intestinal disorders in RSV-infected young mice and to explore the potential mechanism. STUDY DESIGN AND METHODS: Lung inflammation was induced by RSV, and cytokine antibody arrays were used to clarify the effectiveness of ZTOI in RSV pneumonia. Subsequently, key therapeutic targets of ZTOI against RSV pneumonia were identified through multi-factor detection and further confirmed. The potential therapeutic material basis of ZTOI in target tissues was determined by non-target mass spectrometry. After confirming that the pharmacological substances of ZTOI can reach the intestine, we used 16S rRNA-sequencing technology to study the effect of ZTOI on the intestinal bacteria. RESULTS: In the RSV-induced mouse lung inflammation model, ZTOI significantly reduced the levels of serum myeloperoxidase, serum amyloid A, C-reactive protein, and thymic stromal lymphoprotein; inhibited the mRNA expression of IL-10 and IL-6; and decreased pathological changes in the lungs. Immunofluorescence and qPCR experiments showed that ZTOI reduced RSV load in the lungs. According to cytokine antibody arrays, platelet factor 4 (PF4), a weak chemotactic factor mainly synthesized by megakaryocytes, showed a concentration-dependent change in lung tissues affected by ZTOI, which could be the key target for ZTOI to exert anti-inflammatory effects. Additionally, sesquiterpenes were enriched in the lungs and intestines, thereby exerting anti-inflammatory and regulatory effects on gut microbiota. CONCLUSION: ZTOI can protect from lung inflammation via PF4 and regulate gut microbiota disorder in RSV-infected young mice by sesquiterpenes, which provides reference for its clinical application in RSV-induced lung diseases.

Investigation of Metabolic and Inflammatory Disorder in the Aging FGF21 Knockout Mouse.

Aging is a physiological condition accomplished with persistent low-grade inflammation and metabolic disorders. FGF21 has been reported to act as a potent longevity determinant, involving inflammatory response and energy metabolism. In this study, we engineered aging FGF21 knockout mice of 36-40 weeks and observed that FGF21 deficiency manifests a spontaneous inflammatory response of lung and abnormal accumulation of lipids in liver. On one hand, inflamed state in lungs and increased circulating inflammatory cytokines were found in FGF21 knockout mice of 36-40 weeks. To evaluate the ability of FGF21 to suppress inflammation, a subsequent study found that FGF21 knockout aggravated LPS-induced pulmonary exudation and inflammatory infiltration in mice, while exogenous administration of FGF21 reversed these malignant phenotypes by enhancing microvascular endothelial junction. On the other hand, FGF21 knockout induces fatty liver in aging mice, characterized by excessive accumulation of triglycerides within hepatocytes. Further quantitative metabolomics and lipidomics analysis revealed perturbed metabolic profile in liver lacking FGF21, including disrupted glucose and lipids metabolism, glycerophospholipid metabolism, and amino acid metabolism. Taken together, this investigation reveals the protective role of FGF21 during aging by weakening the inflammatory response and balancing energy metabolism.

Impact of Skeletal Muscle Loss and Sarcopenia on Outcomes of Locally Advanced Esophageal Cancer during Neoadjuvant Chemoradiation.

BACKGROUND: The impact of changes in skeletal muscle and sarcopenia on outcomes during neoadjuvant chemoradiotherapy (NACR) for patients with esophageal cancer remains controversial. PATIENTS AND METHODS: We retrospectively analyzed the data of patients with locally advanced esophageal squamous cell cancer who received NACR followed by esophagectomy between June 2013 and December 2021. The images at third lumbar vertebra were analyzed to measure the cross-sectional area and calculate skeletal muscle index (SMI) before and after NACR. SMI less than 52.4 cm2/m2 for men and less than 38.5 cm2/m2 for women were defined as sarcopenia. The nonlinearity of the effect of percent changes in SMI (ΔSMI%) to survival outcomes was assessed by restricted cubic splines. RESULTS: Overall, data of 367 patients were analyzed. The survival outcomes between sarcopenia and non-sarcopenia groups had no significant differences before NACR. However, patients in post-NACR sarcopenia group showed poor overall survival (OS) benefit (P = 0.016) and poor disease-free survival (DFS) (P = 0.043). Severe postoperative complication rates were 11.9% in post-NACR sarcopenia group and 5.0% in post-NACR non-sarcopenia group (P = 0.019). There was a significant non-linear relationship between ΔSMI% and survival outcomes (P < 0.05 for non-linear). On the multivariable analysis of OS, ΔSMI% > 12% was the independent prognostic factor (HR 1.76, 95% CI 1.03-2.99, P = 0.039) and significant difference was also found on DFS analysis (P = 0.025). CONCLUSIONS: Patients with post-neoadjuvant chemoradiotherapy sarcopenia have worse survival and adverse short-term outcomes. Moreover, greater loss in SMI is associated with increased risks of death and disease progression during neoadjuvant chemoradiotherapy, with maximum impact noted with SMI loss greater than 12%.

Mesenchymal stem cell-derived extracellular vesicles in skin wound healing: roles, opportunities and challenges.

Skin wounds are characterized by injury to the skin due to trauma, tearing, cuts, or contusions. As such injuries are common to all human groups, they may at times represent a serious socioeconomic burden. Currently, increasing numbers of studies have focused on the role of mesenchymal stem cell (MSC)-derived extracellular vesicles (EVs) in skin wound repair. As a cell-free therapy, MSC-derived EVs have shown significant application potential in the field of wound repair as a more stable and safer option than conventional cell therapy. Treatment based on MSC-derived EVs can significantly promote the repair of damaged substructures, including the regeneration of vessels, nerves, and hair follicles. In addition, MSC-derived EVs can inhibit scar formation by affecting angiogenesis-related and antifibrotic pathways in promoting macrophage polarization, wound angiogenesis, cell proliferation, and cell migration, and by inhibiting excessive extracellular matrix production. Additionally, these structures can serve as a scaffold for components used in wound repair, and they can be developed into bioengineered EVs to support trauma repair. Through the formulation of standardized culture, isolation, purification, and drug delivery strategies, exploration of the detailed mechanism of EVs will allow them to be used as clinical treatments for wound repair. In conclusion, MSC-derived EVs-based therapies have important application prospects in wound repair. Here we provide a comprehensive overview of their current status, application potential, and associated drawbacks.

FGF10 mitigates doxorubicin-induced myocardial toxicity in mice via activation of FGFR2b/PHLDA1/AKT axis.

Doxorubicin is a common chemotherapeutic agent in clinic, but myocardial toxicity limits its use. Fibroblast growth factor (FGF) 10, a multifunctional paracrine growth factor, plays diverse roles in embryonic and postnatal heart development as well as in cardiac regeneration and repair. In this study we investigated the role of FGF10 as a potential modulator of doxorubicin-induced cardiac cytotoxicity and the underlying molecular mechanisms. Fgf10+/- mice and an inducible dominant negative FGFR2b transgenic mouse model (Rosa26rtTA; tet(O)sFgfr2b) were used to determine the effect of Fgf10 hypomorph or blocking of endogenous FGFR2b ligands activity on doxorubicin-induced myocardial injury. Acute myocardial injury was induced by a single injection of doxorubicin (25 mg/kg, i.p.). Then cardiac function was evaluated using echocardiography, and DNA damage, oxidative stress and apoptosis in cardiac tissue were assessed. We showed that doxorubicin treatment markedly decreased the expression of FGFR2b ligands including FGF10 in cardiac tissue of wild type mice, whereas Fgf10+/- mice exhibited a greater degree of oxidative stress, DNA damage and apoptosis as compared with the Fgf10+/+ control. Pre-treatment with recombinant FGF10 protein significantly attenuated doxorubicin-induced oxidative stress, DNA damage and apoptosis both in doxorubicin-treated mice and in doxorubicin-treated HL-1 cells and NRCMs. We demonstrated that FGF10 protected against doxorubicin-induced myocardial toxicity via activation of FGFR2/Pleckstrin homology-like domain family A member 1 (PHLDA1)/Akt axis. Overall, our results unveil a potent protective effect of FGF10 against doxorubicin-induced myocardial injury and identify FGFR2b/PHLDA1/Akt axis as a potential therapeutic target for patients receiving doxorubicin treatment.

Multiple anti-inflammatory mechanisms of Zedoary Turmeric Oil Injection against lipopolysaccharides-induced acute lung injury in rats elucidated by network pharmacology combined with transcriptomics.

BACKGROUND: Prospects for the drug treatment of acute lung injury (ALI) is unpromising. Managing inflammation can prevent ALI from progressing and minimize further deterioration. Zedoary turmeric oil injection (ZTOI), a patented traditional Chinese medicine (TCM) that has been used against ALI, has shown significant anti-inflammatory effects. However, the mechanisms underlying these effects remain unclear. PURPOSE: Elucidate the anti-inflammatory mechanism by which ZTOI acts against ALI in rats using an ingredients-targets-pathways (I-T-P) interaction network. STUDY DESIGN AND METHODS: The key ingredients of ZTOI were characterized using UPLC-MS/MS combined with literature mining. The target profiles of each ingredient were established using drug-target databases. The anti-inflammatory activity of ZTOI against lipopolysaccharides (LPS)-induced rat ALI was validated using histopathology and inflammatory factor assessments. The therapeutic targets of ZTOI were screened by integrating transcriptomic results of lung tissues with protein-protein interaction (PPI) expansion. Using KEGG pathway enrichment, an I-T-P network was established to determine the essential interactions among ingredients, targets, and pathways of ZTOI against lung inflammation in ALI. Molecular docking and immunofluorescence staining were utilized to confirm the accuracy of the I-T-P network. RESULTS: A total of 11 sesquiterpenes, whose target profiles may characterize the potential function of ZTOI, were identified as key ingredients. In the ALI rat model, ZTOI can alleviate lung inflammation by decreasing the levels of C-reactive protein, interleukin-6, interleukin-1ß, and tumor necrosis factor α both in serum and lung tissues. Based on our biological samples, transcriptomics, PPI network expansion, and KEGG pathway enrichment, 11 ingredients, 174 targets, and 8 signaling pathways were linked in the I-T-P networks. From these results, ZTOI could be inferred to exert multiple anti-inflammatory effects against ALI through Toll-like receptor, NF-kappa B, RIG-I-like receptor, TNF, NOD-like receptor, IL-17, MAPK, and the Toll and Imd signaling pathways. In addition, two significantly regulated targets in the transcriptome, Usp18 and Map3k7, could be the essential anti-inflammatory targets of ZTOI. CONCLUSION: By integrating network pharmacology with ingredient identification and transcriptomics, we show the multiple anti-inflammatory mechanisms by which ZTOI acts against ALI on an I-T-P level. This work also provides a methodological reference for related research into TCM.

The comparisons of neoadjuvant chemoimmunotherapy versus chemoradiotherapy for oesophageal squamous cancer.

OBJECTIVES: The aim of this study was to evaluate the short-term outcomes of neoadjuvant chemoimmunotherapy (NACI) followed by oesophagectomy for locally advanced oesophageal squamous carcinoma. METHODS: Patients receiving NACI or chemoradiotherapy between September 2019 and September 2021 were identified. The primary outcomes were tumour response and survival. Secondary outcomes were toxic effects and postoperative complications. The propensity score matching for enrolled patients was performed. RESULTS: Data of 149 patients with clinical stage II-IV oesophageal squamous cancer, including 55 receiving NACI and 94 receiving neoadjuvant chemoradiotherapy (NACR), were analysed after propensity score matching. With regard to tumour response score, 24 (43.6%) and 59 (62.8%) patients were scored 0/1 in the NACI and NACR groups, respectively (P = 0.023). Of note, 17 (30.9%) patients in the NACI group achieved pathological complete response (CR) (ypT0N0), while 48 (51.1%) patients in NACR group achieved pathological CR (P = 0.026). NACR was associated with the higher risk of postoperative pneumonia (P = 0.034) and less lymph nodes and stations dissected (P ≤ 0.001). The 1-year cumulative overall survival rate was 94.5% and 86.2% in the NACI and NACR groups, respectively (P = 0.170). CONCLUSIONS: We found that NACI compared with NACR was associated with lower pneumonia rate and was safe and feasible for locally advanced oesophageal squamous cancer. However, the tumour regression score and the pathological CR rate of patients treated with neoadjuvant immunotherapy were lower than those of patients treated with NACR. The short-term follow-up results were comparable between 2 treatment modalities.

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.

Does robotic-assisted thymectomy have advantages over video-assisted thymectomy in short-term outcomes? A systematic view and meta-analysis.

OBJECTIVES: A thymic epithelial tumour is the most common primary tumour in the anterior mediastinum of adults. A few retrospective studies compared the short-term outcomes between robotic-assisted thymectomy (RAT) and video-assisted thymectomy (VAT). So, it is necessary to conduct a meta-analysis to further compare these 2 surgical techniques. METHODS: EMBASE, Medline and Web of Science were used. Thesaurus terms and medical subject headings were used in Medline and EMBASE, respectively. The Newcastle-Ottawa scale was used for grading because the included studies were all case-control studies. RESULTS: Nine studies were included in the meta-analysis with a total of 723 patients, including 315 patients in the RAT group and 408 patients in the VAT group. The meta-analysis [odds ratio (OR) 0.24, 95% confidence interval (CI) 0.06-0.94; P = 0.041], indicating that RAT yielded a significantly lower rate of conversion compared with VAT. Duration of drainage with RAT was significantly less than that with VAT (weighted mean difference = -1.10; 95% CI -1.98 to -0.22; P = 0.014). The pooled analysis (weighted mean difference = -103.6; 95% CI -199.21 to -7.98; P = 0.034) suggested that patients in the RAT group had less drainage than those in the VAT group. The recurrence rates in both groups were comparable (OR 0.19, 95% CI 0.03-1.20; P = 0.078). CONCLUSIONS: RAT has advantages over VAT in terms of short-term outcomes such as shorter duration of drainage, less total drainage and a lower rate of conversion. The recurrence rate was comparable between the 2 techniques. Therefore, RAT could be considered as an alternative treatment for diseases of the thymus.

Predictive value of postoperative C-reactive protein-to-albumin ratio in anastomotic leakage after esophagectomy.

INTRODUCTION: Among the many possible postoperative complications, anastomotic leakage (AL) is the most common and serious. Therefore, the purpose of this study was to explore the ability of various inflammatory and nutritional markers to predict postoperative AL in patients after esophagectomy. METHODS: A total of 273 patients were retrospectively evaluated and enrolled into this study. Perioperative, surgery-related, tumor-related and laboratory tests data were extracted and analyzed. The discriminatory ability and optimal cut-off value was evaluated according to the receiver operating characteristic (ROC) curve analysis. Univariate and multivariate analyses were performed to access the potential risk factors for AL. RESULTS: The overall incidence of AL was 12.5% (34/273). C-reactive protein-to-albumin ratio (CRP/ALB ratio) [AUC 0.943 (95% confidence interval (CI) = 0.911-0.976, p <  0.001)] and operation time [AUC 0.747 (95% CI = 0.679-0.815, p <  0.001)] had the greatest discrimination on AL prediction. Multivariate analysis demonstrated that CRP/ALB ratio and operation time were two independent risk factors for AL, and CRP/ALB ratio (OR = 102.909, p <  0.001) had an advantage over operation time (OR = 9.363, p = 0.020; Table 3). CONCLUSION: Operation time and postoperative CRP/ALB ratio were two independent predictive indexes for AL. Postoperative CRP/ALB ratio greater than 3.00 indicated a high risk of AL. For patients with abnormal postoperative CRP/ALB ratio, early non-operative treatment or surgical intervention are needed to reduce the serious sequelae of AL.

The prognostic value of modified NUTRIC score for patients in cardiothoracic surgery recovery unit: A retrospective cohort study.

BACKGROUND: Malnutrition is highly prevalent in critically ill patients. The modified Nutrition Risk in the Critically ill (mNUTRIC) score has been introduced to evaluate the nutritional risk of patients in an intensive care unit (ICU). The mNUTRIC score is a predictive factor of mortality for patients in a medical or mixed ICU, whereas the relationship between mNUTRIC and prognosis of patients in a cardiothoracic surgery recovery unit (CSRU) is unclear and related researches are limited. METHODS: We conducted this retrospective cohort study to explore the value of mNUTRIC score in CSRU patients. We identified totally 4059 patients from the Multiparameter Intelligent Monitoring in Intensive Care III (MIMIC III) database. RESULTS: The optimal cut-off value of mNUTRIC score was 4 and a total of 1498 (36.9%) patients were considered to be at high nutritional risk (mNUTRIC ≥ 4). A multivariate logistic regression model indicated that patients at high nutritional risk have higher hospital mortality compared to those at low nutritional risk (odds ratio = 2.49, 95% confidence interval (CI) = 1.32-4.70, p = 0.005]. Furthermore, a Cox regression model was established adjusted for age, white blood cell and body mass index. The Kaplan-Meier curve indicated that patients at high nutritional risk have poorer 365-days [hazard ratio (HR) = 1.76, 95% CI = 1.30-2.37, p < 0.001] and 1000-days (HR = 2.30, 95% CI = 1.87-2.83, p < 0.001) overall survival. CONCLUSIONS: The mNUTRIC score could not only predict hospital mortality, but also be an independent prognostic factor for long-term survival in CSRU patients. More well-designed clinical trials are needed to verify and update our findings.

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.

Controlling nutritional status is a prognostic factor for patients with lung cancer: a systematic review and meta-analysis.

BACKGROUND: Nowadays, controlling nutritional status (CONUT) has been used as a prognostic factor in variety of cancers. However, no consensus has been reached on the prognostic value of CONUT in lung cancer. In this study, we aim to investigate the role of CONUT in survival of patients with lung cancer. METHODS: EMBASE, web of science, and Medline were used to search articles in English-language journals. The association between CONUT score and survival of patients with lung cancer was evaluated by using pooled HRs and their 95% CIs. Chi-square test and I-Square was used to test heterogeneity among studies. Analyses were all performed using Stata 13.0 (Stata Corporation, College Station, TX). RESULTS: Eight studies with 1,836 patients were eventually included in this meta-analysis. The pooled results showed that high CONUT score had an unfavorable impact on OS (HR =1.63, 95% CI: 1.30-2.04), DFS (HR =1.75, 95% CI: 1.35-2.26), CSS (HR =1.45, 95% CI: 1.01-2.07) and PFS (HR =1.67, 95% CI: 0.99-2.35), compared with those with low-CONUT. CONCLUSIONS: CONUT can be used as a predictor of prognosis in patients with lung cancer. High-CONUT score was significantly associated with poor OS, DFS, CSS and PFS.

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.

Enteral immunonutrition versus enteral nutrition for patients undergoing esophagectomy: a randomized controlled trial.

BACKGROUND: In recent years, immunonutrition has been introduced and proposed to have a positive modulatory effect on inflammatory and immune responses and gut function for surgical patients, especially for patients undergoing gastrointestinal cancer resection. We conducted this parallel-group, randomized and double-blind clinical controlled trial to investigate the efficacy of perioperative enteral immunonutrition (EIN) on clinical and immunological outcomes of patients undergoing esophageal resection. METHODS: A randomized, parallel-group, double-blind, clinical trial was conducted between December 1, 2017 and March 1, 2018. This study enrolled 120 patients with esophageal cancer. And 112 patients were divided into two groups randomly: EIN group and enteral nutrition (EN) group. The EIN contained extra immunonutritional substrates, including a consistent combination of arginine, RNA and the omega-3 fatty acids compared with EN. Immune indicators were measured at preoperative day 7, postoperative day (POD) 1, 3, 7 and post-discharge day (PDD) 30. RESULTS: There were 56 participants randomized to each group. Finally, 53 patients in EIN and 50 patients in EN were analyzed. Immune indicator was the primary outcome in this study. EIN yielded a significantly lower rate of CD8/CD3 (%) at POD 3 compared with EN group (P=0.005). The rate of CD4/CD8 (%) in EIN group was higher than that in EN group at POD3 (P=0.004). The serum levels of IgM at POD 3 and 7 were significantly higher in EN group compared with EIN group (P=0.025 and P=0.009, respectively). The rate of NK (%) and the serum level of IgA were significantly higher in EIN group compared with EN group at PDD 30 (P=0.022 and P=0.041, respectively). No significant differences were found in 2-year progressionfree survival and overall survival. CONCLUSIONS: Immunonutrition is a safe and feasible nutritional treatment, which has a positive modulatory impact on immune responses after esophagectomy. Although no significant difference was found in clinical and survival outcomes between EIN and EN groups, immunonutrition could still have a positive effect on immunological function of patients undergoing esophagectomy.

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.

Comparison of the progression-free survival between robot-assisted thymectomy and video-assisted thymectomy for thymic epithelial tumors: a propensity score matching study.

BACKGROUND: Robotic system was recently introduced to assist surgeons in performing thymectomy. However, whether robot-assisted thoracoscopic thymectomy (RATT) could replace video-assisted thoracoscopic thymectomy (VATT) and be considered as a superior treatment for thymic epithelial tumors is still controversial. The aim of this study was to evaluate the progression-free survival (PFS) and short-term clinical outcomes in patients undergoing RATT or VATT by comparing the matched two groups after performing propensity score analysis. METHODS: We retrospectively reviewed the clinical data of 295 patients diagnosed with thymic epithelial tumors. There were 60 patients in RATT group and 235 in VATT group. Propensity score matching was done between two groups with variables of age, gender, tumor size, organization histologic classification, original Masaoka stages, presence of myasthenia gravis (MG) and adjuvant therapy. Sixty patients from the RATT group and 60 from the VATT group were matched, fitting the model. The PFS and short-term clinical outcomes of matched groups were compared. RESULTS: After matching, the surgical time in RATT groups was significant shorter than that in VATT groups (P=0.042). Loco-regional recurrence and distal metastasis were detected in 4 patients with thymoma and 1 patient with thymic carcinoma in RATT group and in 25 patients with thymoma and 3 patients with thymic carcinoma in VATT group before matching. PFS were estimated in only thymoma cases. The PFS in RATT group (n=55) intended to be longer than that in VATT group (n=58) after matching (5-year PFS rate: 81.5% and 75.4%, respectively; log-rank P=0.095). CONCLUSIONS: RATT has the superiorities over VATT on short-term outcomes due to enabling surgeons to operate in a stable and comfortable environment. Meanwhile, RATT yielded a longer PFS compared with VATT, although the difference was not significant. Therefore, RATT could be considered as a standard approach for the treatment of thymic epithelial tumors.

Paravertebral block with modified catheter under surgeon's direct vision after video-assisted thoracoscopic lobectomy.

BACKGROUND: Paravertebral block (PVB) conducted by epidural catheter is a prevalent pain management for patients undergoing video-assisted thoracoscopic surgery (VATS) lobectomy. The aim of this study was to assess the efficacy and safety of paravertebral block with a modified PVB (MPVB) catheter under surgeon's direct vision after video-assisted thoracoscopic lobectomy. METHODS: Three hundred fifty-six patients undergoing VATS lobectomy were retrospectively reviewed and divided into two groups consecutively according to the catheter applied in PVB procedure (PVB group and MPVB group). In the MPVB group, a modified catheter with a flexible forepart and more apertures distributing along the forepart than the conventional epidural catheter was introduced. An infusion pump containing of 150 mL mixture was connected to the catheter to provide sustained regional analgesia. Intramuscular dezocine 10 mg was administered as a rescue medication when necessary. Postoperative pain management effect was assessed by visual analog scale (VAS) at rest and on coughing. Spirometry values and blood gas analysis were monitored and recorded for the first 3 postoperative days (PODs). Analgesia-related adverse events, characteristics of PVB procedure and postoperative major complication were also compared between the two groups. RESULTS: There were 172 patients who received PVB with conventional epidural catheter in the PVB group, and 184 patients were performed PVB with modified paravertebral catheter in the MPVB group. Significantly lower pain score at rest was found in MPVB group at 24 h postoperatively (P=0.006). The pain score on coughing in MPVB group was significantly lower than that in PVB group at 12 and 24 h postoperatively (P=0.037 and P<0.001, respectively). Patients needing for rescue medication was significantly lower in the MPVB group (P=0.028). The incidence of pleural perforation was lower in the MPVB group (P=0.020). Postoperative spirometry values revealed comparable pulmonary function between the two groups, and arterial blood gas analysis showed a normal range of pH and PaCO2 in both groups. There was no significant difference of analgesia-related adverse events as well as major complications between the two groups. CONCLUSIONS: PVB with modified catheter under surgeon's direct vision was effective and safe after video-assisted thoracoscopic lobectomy.

Modified Collard versus end-to-side hand-sewn anastomosis for cervical anastomosis after McKeown esophagectomy.

BACKGROUND: According to previously published studies, esophagectomy with modified Collard anastomosis has been reported to have low incidences of anastomotic leak and stricture. However, the optional anastomotic method after esophagectomy is still controversial. We conducted this study to compare the incidence of postoperative anastomotic stricture formation and dysphagia over three years after an esophagectomy with modified Collard anastomosis (MC) or end-to-side (ETS) hand-sewn anastomosis. Meanwhile, the early postoperative anastomotic leakage and other complications, hospital stay and 30- and 90-day mortality were also evaluated. METHODS: The clinical data of 905 patients undergoing McKeown esophagectomy were retrospectively reviewed. The rate of postoperative stricture formation after three years was demonstrated by stricture-free survival which is the primary end-point of this study. The incidence of dysphagia, first time of onset of stricture and number of dilatations were also recorded during follow-up. RESULTS: The incidence of anastomotic leak tended to be higher in the MC group compared with that in the ETS group (13.0% vs. 8.7%, P = 0.064). The rates of anastomotic stricture in the MC group were significantly less than in the ETS group (P = 0.004). The number of dilatations in the MC group were significantly greater than those in the ETS group (2.34 vs. 2.46, P = 0.011). CONCLUSIONS: A modified Collard cervical esophagogastric anastomosis was associated with lower rates of anastomotic stricture and dysphagia, compared with ETS hand-sewn anastomosis. However, the modified Collard anastomosis is accompanied by an increased anastomotic leakage rate.