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%.

MTHFD1L confers a poor prognosis and malignant phenotype in esophageal squamous cell carcinoma by activating the ERK5 signaling pathway.

MTHFD1L, a key enzyme of folate metabolism, is seldom reported in cancer. In this study, we investigate the role of MTHFD1L in the tumorigenicity of esophageal squamous cell carcinoma (ESCC). ESCC tissue microarrays (TMAs) containing 177 samples from 109 patients were utilized to evaluate whether MTHFD1L expression, determined using immunohistochemical analysis, is a prognostic indicator for ESCC patients. The function of MTHFD1L in the migration and invasion of ESCC cells was studied with wound healing, Transwell, and three-dimensional spheroid invasion assays in vitro and a lung metastasis mouse model in vivo. The mRNA microarrays and Ingenuity pathway analysis (IPA) were used to explore the downstream of MTHFD1L. Elevated expression of MTHFD1L in ESCC tissues was significantly associated with poor differentiation and prognosis. These phenotypic assays revealed that MTHFD1L significantly promote the viability and metastasis of ESCC cell in vivo and in vitro. Further detailed analyses of the molecular mechanism demonstrated that the ESCC progression driven by MTHFD1L was through up-regulation ERK5 signaling pathways. These findings reveal that MTHFD1L is positively associated with the aggressive phenotype of ESCC by activating ERK5 signaling pathways, suggesting that MTHFD1L is a new biomarker and a potential molecular therapeutic target for ESCC.

The development and progress of nanomedicine for esophageal cancer diagnosis and treatment.

Esophageal cancer (EC) is a common gastrointestinal malignancy with poor prognosis and high mortality. Although combined therapeutic strategies have been developed, the 5-year survival rate of patients with EC remains relatively poor. Conventional anti-cancer drug delivery techniques have some shortcomings, such as nontargeted delivery and nonspecific toxicity. Nanoparticles (NPs) provide a promising platform for delivering drugs in various therapeutic modalities for EC, which possess several remarkable advantages in cancer therapy, such as reduced side effects, prolonged circulation time, and preferential accumulation at the tumor site. In this review, we summarized various types of NPs applied in the treatment of EC, including polymers, micelles, liposomes, inorganic NPs and organic NPs. Meanwhile, we discussed the efficacy and safety of newly designed nanomedicine in various treatments of EC, including chemotherapy, radiotherapy, gene therapy, photodynamic therapy (PDT), photothermal therapy (PTT), and their synergetic therapy. In addition, nanomedicine applied in tumor imaging and diagnoses were also reviewed. Current studies have suggested the potential advantages of nanoformulations over conventional formulations. More researches to promote clinical translation of nanomedicine for EC are anticipated in the future.

The Prognostic Value of Nodal Skip Metastasis in Patients with Esophageal Cancer: A Systematic Review and Meta-Analysis.

BACKGROUND: Esophageal cancer (EC) is the sixth leading cause of cancer deaths worldwide. Nodal skip metastasis (NSM), a common form of lymphatic spread in EC, can be defined as the metastatic involvement of distant lymph nodes (LNs) without prior involvement of adjacent LNs. The results of the previous studies investigating the association between NSM and survival outcomes in patients with EC were inconsistent and even contradictory. The aim of this systematic review and meta-analysis is to investigate the prognostic value of NSM and to summarize the NSM definitions of EC in previous studies. METHODS: Four databases were used in this meta-analysis. The association between NSM and overall survival (OS) was evaluated by using pooled HRs and their 95% confidence interval (CI). The sensitivity analysis and funnel plot were used to assess the publication bias. RESULTS: Nine studies were included in this meta-analysis. The pooled results of meta-analysis indicated that there was no significant association between NSM and OS (HR = 0.99, 95% CI: 0.75-1.31; P = 0.951). Meanwhile, according to the results of sub-group analysis on the basis of histological feature, method of lymphadenectomy, node staging system, and NSM definitions, no significant association was found between NSM and OS. CONCLUSIONS: On the basis of available evidences, NSM could not be used as a prognostic factor for patients with EC. For future studies investigating the prognostic value of NSM, only three-field lymphadenectomy with adequate harvested LNs can be performed. NSM definitions based on lymph node station and anatomical compartment could both be feasible classification for EC.

Overexpressed COL3A1 has prognostic value in human esophageal squamous cell carcinoma and promotes the aggressiveness of esophageal squamous cell carcinoma by activating the NF-κB pathway.

Alpha-1 Type Ⅲ Collagen (COL3A1) encodes the Collagen alpha-1(Ⅲ) chain, which is a fibrillar collagen that exists in extensile connective tissues. Few studies have reported its role in tumorigenicity. In the present study, we identified that COL3A1 protein and mRNA expression levels were considerably up-regulated in esophageal squamous cell carcinoma (ESCC) cells in comparison with normal esophageal squamous epithelial cells (P < 0.05). Immunohistochemical (IHC) analysis of 114 paraffin-embedded archived ESCC tissues demonstrated that COL3A1 expression was positively correlated with the postoperative T stage. Univariate and multivariable analysis demonstrated that COL3A1 expression was an independent poor prognostic factor for overall survival in the whole cohort. Silencing COL3A1 inhibited, while overexpressing COL3A1 promoted, the proliferation, migration, and invasion of ESCC cells. Furthermore, down-regulation of COL3A1 expression also suppressed the growth of ESCC in subcutaneous xenograft mouse models and inhibited ESCC metastasis in lung metastasis mouse models. In addition, we proved that the tumor-promoting effect of COL3A1 on ESCC cells was related to the activation of NF-κB signaling pathway. These findings indicate that COL3A1 confers a poor prognosis and malignant phenotype by activating the NF-κB pathway in ESCC, potentially representing a novel biomarker and/or providing a new curative target for ESCC.

Acid-Responsive Aggregated Gold Nanoparticles for Radiosensitization and Synergistic Chemoradiotherapy in the Treatment of Esophageal Cancer.

Radiotherapy and chemotherapy are limited by insufficient therapeutic efficacy of low-dose radiation and nonspecific drug biodistribution. Herein, an acid-responsive aggregated nanosystem (AuNPs-D-P-DA) loaded with doxorubicin (DOX) is designed for radiosensitization and synergistic chemoradiotherapy. In response to the acid microenvironment of esophageal cancer (EC), small-sized AuNPs-D-P-DA forms large-sized gold nanoparticle (AuNPs) aggregates in tumor tissues to hinder the backflow of AuNPs to the circulation, resulting in enhanced tumor accumulation and retention. Simultaneously, the AuNPs-based radiosensitization is significantly improved because of the high concentration and large size of intratumoral AuNPs, while DOX are delivered and released specifically into tumor cells triggered by the acid microenvironment for chemo-radio synergistic therapy. Acid-responsive AuNPs exacerbate radiation-induced DNA damage, cell apoptosis, cell cycle arrest, and low colony formation ability in vitro and enhance anti-tumor efficacy in vivo compared to un-responsive control. When combined with acid-responsive DOX, the therapeutic efficacy of the formulation is further improved by their synergistic effect. After the treatment of acid-responsive AuNPs plus radiotherapy, fatty acid metabolism is reprogrammed in xenograft models, which provides potential targets for further improvement of radiosensitization. In summary, the acid-responsive AuNPs-D-P-DA nanosystem leverages the radio- and chemotherapeutic synergies of AuNPs-sensitized X-ray irradiation and acid-responsive DOX in the treatment of EC.

The prognostic value of controlling nutritional status score on esophageal squamous cell carcinoma patients with neoadjuvant therapy followed by esophagectomy-a retrospective research.

Background: A variety of nutritional evaluation parameters has been documented as prognostic indicators in some malignancies. However, the prognostic significance of the controlling nutritional status (CONUT) score, as one of these nutritional indices, in patients with esophageal squamous cell carcinoma (ESCC) remains unclear and warrants investigation. Our study sought to elucidate the prognostic value of this nutritional index in ESCC patients who underwent neoadjuvant therapy followed by esophagectomy. Methods: This retrospective study encompassed 314 patients diagnosed with ESCC who underwent neoadjuvant therapy followed by esophagectomy at West China Hospital of Sichuan University between August 2016 and August 2021. CONUT scores were computed at two specific time points: prior to neoadjuvant therapy initiation and before surgery, utilizing serum albumin, total lymphocyte, and cholesterol levels of ESCC patients. Furthermore, the delta CONUT (ΔCONUT) score was derived by subtracting the preoperative CONUT score from the pretreatment CONUT score. The associations between CONUT scores and various survival outcomes were evaluated using Kaplan-Meier methods and Cox regression analysis. Results: Patients with a high preoperative CONUT score demonstrated a higher postoperative complication rate [odds ratio (OR) =2.009, 95% confidence interval (CI): 1.150-3.510, P=0.01] compared to those in the low CONUT group. Multivariate analysis revealed that a ΔCONUT score ≥0 served as an independent negative prognostic indicator for increased postoperative complications (OR =3.008, 95% CI: 1.509-5.999, P=0.002) and poorer overall survival [hazard ratio (HR) =2.388, 95% CI: 1.052-5.422, P=0.04] in ESCC patients who underwent neoadjuvant therapy combined with esophagectomy. Conclusions: A high preoperative CONUT score and a ΔCONUT score ≥0 were indicative of a poor prognostic nutritional status in ESCC patients who had undergone neoadjuvant therapy followed by esophagectomy.

Unraveling the impact of irritability on esophageal diseases: Insights from multivariable Mendelian randomization analysis.

BACKGROUND: Previous studies have suggested a potential association between irritability and the risk of various diseases. However, establishing a causal relationship has remained a significant challenge. To address this issue, we employed Mendelian randomization (MR), a sophisticated approach that leverages genotype data to emulate the conditions of randomized controlled trials. This method enables us to investigate the potential causal link between irritability and the susceptibility to esophageal diseases. METHODS: We conducted an extensive multivariable MR analysis using summary-level data from genome-wide association studies (GWAS) encompassing various esophageal diseases, including gastroesophageal reflux disease (GERD), esophageal cancer (EC), and Barrett's esophagus. Both univariable and multivariable MR analyses were performed to elucidate and confirm the causal association between genetically predicted irritability and the incidence of esophageal diseases. RESULTS: Based on our primary causal effects model utilizing MR analyses with the inverse-variance weighted (IVW) method, genetically predicted irritability was identified as a risk factor for GERD (OR = 2.413; 95 % CI: 1.678-3.470; P = 2.03E-06) and Barrett's esophagus (OR = 2.306; 95 % CI: 1.042-5.101; P = 0.039). However, irritability was not found to be associated with the risk of EC, even after adjusting for BMI, smoking initiation, and alcohol consumption. CONCLUSION: The multivariable MR analysis performed in this study demonstrated a causal relationship between irritability and esophageal diseases. It is imperative to acknowledge the need for further large-scale prospective studies to validate these findings.

A novel tumor staging system incorporating cN status for stratifying early stage esophageal squamous cell carcinoma patients after trimodal therapy.

BACKGROUNDS: The aim of this study is to investigate the prognostic value of cN status for early stage esophageal squamous cell carcinoma (ESCC) patients after neoadjuvant chemoradiotherapy (nCRT) and construct a new staging model for individual survival prediction. METHODS: Patients with ESCC who underwent nCRT and esophagectomy were included in this study. Both the Akaike Information Criterion (AIC) and the Bayesian Information Criterion (BIC) were meticulously ascertained to assess the cogency of each oncological staging system. A discernible abatement in the values of AIC and BIC signifies a model endowed with enhanced predictive prowess and exemplary veracity. RESULTS: A new staging model was established based on ypTNM stage and cN status by precisely stratifying ypI ESCC patients. The novel ypTNM-cN staging demonstrated superior overall survival trend alignment over the AJCC 8th ypTNM staging, with a notably lower AIC of 3143.014 versus 3149.950. This superiority was supported by a BIC of 3146.605 against 3153.541. In the context of disease-free survival outcomes, the emergent ypTNM-cN staging, with an AIC value registering at 3196.057 and a BIC value at 3199.648, distinctively eclipsed the AJCC 8th ypTNM staging, which documented values of 3203.853 and 3207.444, respectively. CONCLUSION: We constructed a new staging system based on ypTNM stage and cN status to precisely stratify the patients with ypI stage. Our new ypTNM-cN staging system provides new insights for classifying stage ypI ESCC and shows reliable classification efficacy for all ESCC patients after nCRT and surgery.

Self-Assembled Acid-Responsive Nanosystem for Synergistic Anti-Angiogenic/Photothermal/Ferroptosis Therapy against Esophageal Cancer.

Esophageal cancer (EC) treatment via anti-angiogenic therapy faces challenges due to non-cytotoxicity and non-specific biodistribution of the anti-angiogenic agents. Hence, the quest for a synergistic treatment modality and a targeted delivery approach to effectively address EC has become imperative. In this study, an acid-responsive release nanosystem (Bev-IR820@FeIII TA) that involves the conjugation of bevacizumab, an anti-angiogenic monoclonal antibody, with TA and Fe3+ to form a metal-phenolic network, followed by loading with the near-infrared photothermal agent (IR820) to achieve combinational therapy, is designed. The construction of Bev-IR820@FeIII TA can be realized through a facile self-assembly process. The Bev-IR820@FeIII TA exhibits tumor-targeting capabilities and synergistic therapeutic effects, encompassing anti-angiogenic therapy, photothermal therapy (PTT), and ferroptosis therapy (FT). Bev-IR820@FeIII TA exhibits remarkable proficiency in delivering drugs to EC tissue through its pH-responsive release properties. Consequently, bevacizumab exerts its therapeutic effects by obstructing tumor angiogenesis, thereby impeding tumor growth. Meanwhile, PTT facilitates localized thermal ablation at the tumor site, directly eradicating EC cells. FT synergistically collaborates with PTT, giving rise to the formation of a reactive oxygen species (ROS) storm, subsequently culminating in the demise of EC cells. In summary, this amalgamated treatment modality carries substantial promise for synergistically impeding EC progression and showcases auspicious prospects for future EC treatment.

Substitute or coexistence? Mediastinoscopy-assisted versus thoracoscope-assisted esophagectomy in esophageal cancer: a meta-analysis of perioperative outcomes and long-term survival.

BACKGROUND: Currently, mediastinoscopy-assisted esophagectomy (MAE) and thoracoscope-assisted esophagectomy (TAE) represent two prevalent forms of minimally invasive esophagectomy extensively employed in the management of esophageal cancer (EC). The aim of this meta-analysis is to assess and compare these two surgical approaches concerning perioperative outcomes and long-term survival, offering valuable insights for refining surgical strategies and enhancing patient outcomes in this field. METHODS: Adhering to PRISMA guidelines, the authors systematically searched PubMed, Web of Science, Cochrane Library, Embase, and CNKI databases until 1 March 2024, for studies comparing MAE and TAE. Outcomes of interest included perioperative outcomes (intraoperative outcomes, postoperative recovery, postoperative complications) and survival rates. Statistical analyses were performed using RevMan 5.4, with heterogeneity dictating the use of fixed or random-effects models. RESULTS: A total of 21 relevant studies were finally included. MAE was associated with significantly shorter operation times [mean difference (MD)=-59.58 min, 95% CI: -82.90 to -36.26] and less intraoperative blood loss (MD=-68.34 ml, 95% CI: -130.45 to -6.23). However, MAE resulted in fewer lymph nodes being dissected (MD=-3.50, 95% CI: -6.23 to -0.78). Postoperative recovery was enhanced following MAE, as evidenced by reduced hospital stays and tube times. MAE significantly reduced pulmonary complications [odds ratio (OR)=0.59, 95% CI: 0.44, 0.81] but increased the incidence of recurrent laryngeal nerve injury (OR=1.84, 95% CI: 1.30, 2.60). No significant differences were observed in anastomotic leakage, chylothorax, cardiac complications, wound infections, and gastric retention between MAE and TAE. The long-term survival outcomes showed no statistical difference [hazard ratio (HR)=1.05, 95% CI: 0.71, 1.54]. CONCLUSIONS: MAE offers advantages in reducing operation time, blood loss, and specific postoperative complications, particularly pulmonary complications, with a shorter recovery period compared to TAE. However, it poses a higher risk of recurrent laryngeal nerve injury and results in fewer lymph nodes being dissected. No difference in long-term survival was observed, indicating that both techniques have distinct benefits and limitations. These findings underscore the need for personalized surgical approaches in EC treatment, considering individual patient characteristics and tumor specifics.

Lymphovascular and Perineural Invasion After Neoadjuvant Therapy in Esophageal Squamous Carcinoma.

BACKGROUND: Lymphovascular invasion and perineural invasion are unfavorable prognostic factors in patients with esophageal squamous cell carcinoma. However, the prevalence and prognostic importance of lymphovascular invasion and perineural invasion after neoadjuvant chemoradiotherapy in these patients remains unclear. METHODS: We retrospectively reviewed specimens of 321 patients with pathologically diagnosed esophageal squamous cell carcinoma who underwent neoadjuvant chemoradiotherapy in our institution from 2017 to 2020. Lymphovascular invasion and perineural invasion were assessed by hematoxylin and eosin staining. Survival was analyzed using the log-rank test and multivariable Cox regression analysis. RESULTS: Lymphovascular invasion and perineural invasion were present in 12.5% (n = 40) and 17.8% (n = 57) of resection specimens, respectively. Lymphovascular invasion and perineural invasion were significantly more common in patients with advanced cancer (both P < .05). In the univariate analyses, lymphovascular invasion and perineural invasion were associated with shorter overall survival and disease-free survival. Multivariable analysis revealed that lymphovascular invasion after neoadjuvant therapy was an independent adverse prognostic factor for overall survival and disease-free survival. Subgroup analyses showed that lymphovascular invasion could identify cases with worse overall survival or disease-free survival among node-negative patients, indicating the role of lymphovascular invasion in the precise staging of pN0 patients. CONCLUSIONS: Lymphovascular invasion and perineural invasion were significantly negatively correlated with overall survival and disease-free survival. Lymphovascular invasion was an independent prognostic predictor in esophageal squamous cell carcinoma patients after neoadjuvant chemoradiotherapy. Lymphovascular invasion and perineural invasion should be considered in the histopathology workup for esophageal squamous cell carcinoma patients after neoadjuvant chemoradiotherapy.

The prognostic value of sarcopenia in oesophageal cancer: A systematic review and meta-analysis.

The loss of skeletal muscle mass and function is defined as sarcopenia, which might develop in elderly patients with cancers. It has been indicated as a potential negative factor in the survival of patients with malignant tumours. The aim of this systematic review and meta-analysis was to evaluate the associations between sarcopenia and survival outcomes or postoperative complications in patients with oesophageal cancer (EC). Web of Science, Embase, Medline, and Cochrane Library databases were searched until 10 May 2022, using keywords: sarcopenia, oesophageal cancer, and prognosis. Studies investigating the prognostic value of sarcopenia on EC survival were included. Forest plots and summary effect models were used to show the result of this meta-analysis. The quality of included studies was evaluated with the Newcastle-Ottawa Scale (NOS). A total of 1436 studies were identified from the initial search of four databases, and 41 studies were included for the final quantitative analysis. This meta-analysis revealed a significant association between sarcopenia and overall survival (OS) [hazard ratios (HR):1.68, 95% confidence interval (CI):1.54-1.83, P = 0.004, I2  = 41.7%] or disease-free survival (DFS) 1.97 (HR: 1.97, 95% CI: 1.44-2.69, P = 0.007, I2  = 61.9%) of EC patients. Subgroup analysis showed that sarcopenia remained a consistent negative predictor of survival when stratified by different treatment methods, populations, or sarcopenia measurements. Sarcopenia was also a risk factor for postoperative complications with a pooled odds ratio of 1.47 (95% CI: 1.21-1.77, P = 0.094, I2  = 32.7%). The NOS scores of all included studies were ≥6, and the quality of the evidence was relatively high. The results from the study suggested that sarcopenia was significantly associated with both survival outcomes and postoperative complications in EC patients. Sarcopenia should be appropriately diagnosed and treated for improving short-term and long-term outcomes of patients with EC.

Causal relationship between lung diseases and risk of esophageal cancer: insights from Mendelian randomization.

BACKGROUND: An increasing number of cohort studies have indicated a correlation between lung diseases and esophageal cancer, but the exact causal relationship has not been definitively established. Therefore, the objective of this study is to assess the causal relationship between lung diseases and esophageal cancer. METHODS: Single-nucleotide polymorphisms (SNPs) related to lung diseases such as asthma, chronic obstructive pulmonary disease (COPD), lung cancer, and idiopathic pulmonary fibrosis (IPF), along with outcomes data on esophageal cancer, were extracted from public genome-wide association studies (GWAS). A two-sample Mendelian randomization (MR) analysis was then performed using publicly available GWAS data to investigate the potential causal relationship. The effect estimates were primarily calculated using the fixed-effects inverse-variance-weighted method. RESULTS: Totally, 81 SNPs related to asthma among 218,792 participants in GWAS. Based on the primary causal effects model using MR analyses with the inverse variance weighted (IVW) method, asthma was demonstrated a significantly related to the risk of esophageal cancer (OR 1.0006; 95% CI 1.0003-1.0010, p = 0.001), while COPD (OR 1.0306; 95% CI 0.9504-1.1176, p = 0.466), lung cancer (OR 1.0003, 95% CI 0.9998-1.0008, p = 0.305), as well as IPF (OR 0.9999, 95% CI 0.9998-1.0000, p = 0.147), showed no significant correlation with esophageal cancer. CONCLUSIONS: The two-sample MR analysis conducted in this study revealed a positive causal relationship between asthma and esophageal cancer. In contrast, esophageal cancer demonstrated no significant correlation with COPD, lung cancer, or IPF. Further large-sample prospective studies are needed to validate these findings and to provide appropriate recommendations regarding esophageal cancer screening among patients with asthma.

In patients undergoing oesophagectomy does postoperative home enteral nutrition have any impact on nutritional status?

A best evidence topic in thoracic surgery was written according to a structured protocol. The question addressed was 'In patients undergoing oesophagectomy does postoperative home enteral nutrition have any impact on nutritional status?' Altogether, 50 articles were found using the reported search, of which 5 studies represented the best evidence to answer the clinical question. This consisted of 1 systematic review including a meta-analysis of 9 randomized controlled trials (RCTs), 3 RCTs and 1 cohort study. Main outcomes included loss of body weight and body mass index (BMI), change of serum albumin, haemoglobin, total protein and prealbumin, rates of nutritional risk patients and score value of patient-generated subjective global assessment. The meta-analysis concluded that there were significant differences in the loss of body weight and BMI between 2 groups, with higher values observed in the HEN group than that in the control group. One RCT showed that patients receiving HEN had a significantly lower weight loss compared with the control group. However, in another RCT, there was no significant difference between 2 groups in the loss of weight and body BMI. The available evidence shows that patients receiving home enteral nutrition yielded a significantly better BMI and lower decrease in body weight than those without after surgical resection of oesophageal cancer. We conclude that HEN could serve as an effective intervention for patients undergoing oesophagectomy. Moreover, the optimal time for patients receiving HEN could be 4-8 weeks after discharge. Feeding via jejunostomy and nasointestinal tube are feasible and safety approaches for HEN.

Prognostic Value of Geriatric Nutritional Risk Index in Esophageal Carcinoma: A Systematic Review and Meta-Analysis.

Esophageal cancer (EC) is one of the most common cancers worldwide. Malnutrition often leads to poor prognosis of patients with EC. Geriatric nutritional risk index (GNRI) was reported as an objective nutrition-related risk index. We intend to comprehensively review evidence of GNRI in predicting EC prognosis. To explore the influence of GNRI on the long-term survival outcome of patients with EC, a meta-analysis was needed. We searched the Web of Science, Medline, Embase, and the Cochrane Library databases. The association between prognosis of patients with EC and GNRI was evaluated by pooling hazard ratios (HRs) and their corresponding 95% confidence intervals (CIs). The fixed model or random model method was chosen according to the heterogeneity among the studies. Totally, 11 studies with 1785 patients who met the inclusion criteria were eventually included in our meta-analysis. Comparing the lower level GNRI group and the higher level GNRI group, the pooled results showed that lower GNRI had a negative impact on overall survival (OS) (HR: 1.75, 95% CI: 1.45-2.10, P < 0.01) and cancer-specific survival (CSS) (HR: 1.77, 95% CI: 1.19-2.62, P < 0.01), indicating that lower GNRI significantly predicted poor OS. In conclusion, lower GNRI could predict the poor prognosis of patients with EC. Meanwhile, more well-designed randomized controlled trials (RCTs) are needed to confirm the findings.

Trimodal Therapy in Esophageal Squamous Cell Carcinoma: Role of Adjuvant Therapy Following Neoadjuvant Chemoradiation and Surgery.

Background: The aim of this study was to determine the role of adjuvant therapy after neoadjuvant chemoradiotherapy and esophagectomy for esophageal squamous cell carcinoma (ESCC). Methods: The study retrospectively reviewed 447 ESCC patients who underwent neoadjuvant chemoradiotherapy and esophagectomy. Patients were divided into an adjuvant therapy group and no adjuvant therapy group. Propensity score matching was used to adjust the confounding factors. Results: 447 patients with clinical positive lymph nodes and no distant metastasis treated with neoadjuvant chemoradiotherapy and esophagectomy were eligible for analysis. After propensity score matching, there were 120 patients remaining in each group. Patients receiving adjuvant therapy had a significantly shorter post-resection overall survival (OS) and disease-free survival (DFS) when compared to patients not receiving adjuvant therapy (log-rank, OS: p = 0.046, DFS: p < 0.001). Receiving adjuvant therapy is not an independently prognostic factor for OS (hazard ratio (HR): 1.270, HR: 0.846−1.906, p = 0.249) but a significantly unfavorable independent prognostic factor for DFS (HR: 2.061, HR: 1.436−2.958, p < 0.001). Conclusions: The results of our study indicate that adjuvant therapy after neoadjuvant chemoradiotherapy and surgery could reduce the OS and DFS in patients with ESCC. Therefore, adjuvant therapy is not recommended for ESCC patients after neoadjuvant chemoradiotherapy and esophagectomy, especially patients without nodal metastases after neoadjuvant therapy.

Prognostic value of micro-RNA 375, 133, 143, 145 in esophageal carcinoma: A systematic review and meta-analysis.

Many studies have confirmed that micro-RNA (mir) is related to the prognosis of esophageal carcinoma (EC), suggesting the mir could be used to guide the therapeutic strategy of EC. Some of mir molecules are considered as favorable prognostic factors for EC. The purpose of our study is to evaluate the prognostic potential of mir-375, 133, 143, 145 in primary EC, we summarized all the results from available studies, aiming delineating the prognostic role of mir in EC. Relevant studies were identified by searching databases including Medline, Embase, Web of science, Cochrane Library. The studies which explored the prognostic value of mir-375, 133, 143, 145 expressions on survival outcomes in patients with EC were included in this study. The hazard ratios (HR) and their responding 95% confidence interval (CI) were also extracted. A total of 25 studies were collected, including 1260 patients, and the prognostic values of four mirs in EC were analyzed. Survival outcomes including overall survival (OS), progression-free survival (PFS) and disease-free survival (DFS) were used as the primary endpoint to evaluate the prognostic value of mir. The pooled analysis results showed that up-regulation of mir-375 indicated favorable OS (HR=0.50; 95%CI: 0.37-0.69; P<0.001). In addition, the up-regulation of mir-133 (HR=0.40, 95%CI: 0.24-0.65, P<0.001), 143 (HR=0.40, 95%CI: 0.21-0.76, P < 0.001) and 145 (HR=0.55, 95%CI: 0.34-0.90, P<0.001) are also proved as protected factors in EC. Therefore, our study demonstrated that these mirs may have the potential to be used as prognostic biomarkers for EC in clinical practice.