Impact of treatment delays on future survival outcomes in non-surgical patients with esophageal cancer in Shandong Province, China.

The treatment process of tumors in surgical patients is typically prompt and efficient, whereas non-surgical patients are more prone to treatment delay due to various factors. However, the relationship between treatment delay and survival outcomes in non-surgical Esophageal cancer (EC) patients has received limited study. This study aims to evaluate the impact of waiting time from diagnose to treatment on survival outcomes among non-surgical EC patients in Shandong Province, China. Over a 20-year follow-up period, a total of 12,911 patients diagnosed with EC and not receiving surgical intervention were identified from 2000 to 2020. The Kaplan-Meier methodology was employed to determine overall survival (OS) and cancer-specific survival (CSS). Univariate and multivariate Cox regression analyses were performed to evaluate the impact of treatment delays on future outcomes. The nonlinear association between waiting time and survival outcomes was investigated using restricted cubic spline (RCS) functions. The average delay in initiating EC treatment from the initial medical consultation for symptoms of EC was 1.18 months (95%CI=1.16-1.20). Patients with a long delay (≥3 months) in treatment demonstrated significantly lower rates of 1-, 3-, and 5-year OS and CSS compared to those with a brief delay in treatment initiation. A long delay in EC treatment independently associated with an increased risk of mortality from all causes and cancer. The association between waiting time and both all-cause and cause-specific mortality illustrated a pronounced J-shaped pattern. The prolong delay in treatment initiation significantly impacts the OS and CSS outcomes for non-surgical EC patients. Timely administration of treatment has the potential to enhance survival outcomes in patients with EC who are ineligible for surgery, including those in advanced stages without surgical options available.

Gastroesophageal Junction Adenocarcinoma With Skeletal Muscle Metastases: A Case Report and Literature Review.

Esophageal and gastroesophageal junction (GEJ) malignancies are aggressive, and survival is poor once metastasis occurs. The most common sites of metastatic involvement include the liver, lymph nodes, lung, peritoneum, adrenal glands, bone, and brain, while skeletal muscle (SM) involvement is rare. We report a case of a 68-year-old female who presented with intractable emesis for one month and was found to have a primary GEJ adenocarcinoma measuring up to 6.7 cm. Endoscopic biopsy revealed poorly differentiated GEJ adenocarcinoma with positive AE1/AE3 immunostains. Positron emission tomography/computed tomography and magnetic resonance imaging revealed metastases to the omentum and left lower extremity SMs, including the proximal adductor longus, adductor magnus, and gluteus minimus. This study reviews the literature on SM metastasis in esophageal and GEJ cancer, GEJ cancer classification, incidence, treatment, and prognosis.

Low psoas muscle index has a negative impact on survival after minimal invasive esophagectomy for cancer in European men.

INTRODUCTION: Sarcopenia, a key component of frailty in cancer patients, is associated with complicated procedures and worse survival after esophageal resection. The psoas muscle index (PMI) has been implicated as a possible sarcopenia imaging marker. This retrospective study aims to elucidate the effect of PMI and BMI in a cohort in Europe after totally minimally invasive esophagectomy for cancer. METHODS: The study included 318 consecutive adult patients (261 men and 57 women) who underwent minimally invasive esophagectomy for cancer between January 2016 and April 2021 in a German University Hospital. The PMI was measured at the third lumbar vertebra in the preoperative CT scan. The endpoints postoperative complication rates and survival rates were analysed and correlated with PMI and BMI according to gender. RESULTS: Male patients with low PMI (< 5.3 cm2/ m2) had a significantly higher rate of postoperative pulmonary and cardiac complications (p = 0.016, respectively p = 0.018). Low PMI and low BMI (<25 kg/m2) were associated with decreased survival rates in the univariate (p < 0.001) and multivariate analysis in male patients (p = 0.024, respectively 0.004). Having a low PMI (< 5.3 cm2/ m2) was significantly associated with worse overall survival in normal and underweight men (p < 0.001), but not in obese men with a BMI ≥ 25kg/m2 (p = 0.476). CONCLUSION: Preoperative PMI and BMI are valid risk factors regarding postoperative survival after minimal invasive esophagectomy for cancer especially in a male European cohort.

One-carbon metabolism biomarkers and upper gastrointestinal cancer in the Golestan Cohort Study.

Incidence of esophageal and gastric cancer has been linked to low B-vitamin status. We conducted matched nested case-control studies of incident esophageal squamous cell carcinoma (ESCC; 340 case-control pairs) and gastric cancer (GC; 352 case-control pairs) within the Golestan Cohort Study. The primary exposure was plasma biomarkers: riboflavin and flavin mononucleotide (FMN) (vitamin B2), pyridoxal phosphate (PLP) (B6), cobalamin (B12), para-aminobenzoylglutamate (pABG) (folate), and total homocysteine (tHcy); and indicators for deficiency: 3-hydroxykyurenine-ratio (HK-r for vitamin B6) and methylmalonic acid (MMA for B12). We estimated odds ratios (ORs) and 95% confidence intervals (CIs) using conditional logistic regression adjusting for matching factors and potential confounders. High proportions of participants had low B-vitamin and high tHcy levels. None of the measured vitamin B levels was associated with the risk of ESCC and GC, but elevated level of MMA was marginally associated with ESCC (OR = 1.42, 95% CI = 0.99-2.04) and associated with GC (OR = 1.53, 95% CI = 1.05-2.22). Risk of GC was higher for the highest versus lowest quartile of HK-r (OR = 1.95, 95%CI = 1.19-3.21) and for elevated versus non-elevated HK-r level (OR = 1.59, 95% CI = 1.13-2.25). Risk of ESCC (OR = 2.81, 95% CI = 1.54-5.13) and gastric cancer (OR = 2.09, 95%CI = 1.17-3.73) was higher for the highest versus lowest quartile of tHcy. In conclusion, insufficient vitamin B12 was associated with higher risk of ESCC and GC, and insufficient vitamin B6 status was associated with higher risk of GC in this population with prevalent low plasma B-vitamin status. Higher level of tHcy, a global indicator of OCM function, was associated with higher risk of ESCC and GC.

Relationships of omega-3 and omega-6 polyunsaturated fatty acids with esophageal diseases: a two-sample Mendelian randomization analysis.

Introduction: Omega-3 polyunsaturated fatty acids (PUFAs) have been widely studied and used as nutritional supplements because of their anti-inflammatory effects. Previous studies have shown an association between polyunsaturated fatty acids such as omega-3 and omega-6 PUFAs with the development of malignant tumors. However, the relationships of omega-3 and omega-6 PUFAs with esophageal diseases have not been characterized. Methods: Mendelian randomization (MR) is a statistical method for identifying instrumental variables (IVs) from genome-wide association study (GWAS) data, and is associated with little confounding by environmental or other disease-related factors. We used genome-wide association study (GWAS) data from previously published studies on circulating concentrations of omega-3, omega-6, docosahexaenoic acid (DHA) and linoleic acid (LA), as well as esophageal cancer and other esophageal diseases, which were downloaded from the IEU OpenGwas database (https://gwas.mrcieu.ac.uk/) and the GWAS Catalog database (https://www.ebi.ac.uk/). The inverse variance-weighted approach was used as the principal analysis, and the MR-Egger and weighted median methods were used alongside. A series of sensitivity analyses were used to ensure the robustness of the causality estimates. Results: We found that the circulating omega-3 PUFAs concentration was positively associated with esophageal cancer (p = 8 × 10-4), and circulating DHA concentration (the main component of omega-3 in food), was also positively associated with esophageal cancer (p = 2 × 10-2), but no significant association was found between circulating omega-6 PUFAs and esophageal cancer (p = 0.17), and circulating LA concentration (the main component of omega-6 in food), was also no significant associated with esophageal cancer (p = 0.32). We found no significant relationships of circulating omega-3 and omega-6 PUFAs concentration with four other esophageal diseases. Conclusion: This study indicates that higher levels of circulating omega-3 PUFAs and DHA concentrations may be a risk factor for the development of esophageal cancer. Conversely, an increased omega-6/omega-3 ratio may serve as a protective factor against esophageal cancer. These findings have significant implications for the clinical application of omega-3 PUFAs and the prevention and treatment of esophageal cancer.

The Investigation of Quercus Infectoria Gall Aqueous Extract Effect on the Cell Proliferation, Apoptosis and Expression of CCND1, TP53, BCL2 and BAX Genes in Cell Line of Lung, Gastric and Esophageal Cancers.

Background: The therapeutic potential of Quercus infectoria (QI) gall, including its anti-inflammatory, antioxidant, and anticancer properties, is well-known. However, its impact on lung, gastric, and esophageal cancer cells remain unclear. This study aims to explore the effects of QI gall aqueous extract on cell viability, apoptosis, and gene expression in A549, BGC823, and KYSE-30 cell lines. Methods: A549, BGC823, and KYSE-30 cells were seeded in complete medium and incubated with different concentrations of QI gall extract for 24 hours. Cell viability was measured by an MTT [3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyl tetrazolium bromide] assay. The induction of apoptosis was assessed through flow cytometric analysis after the adding FITC-conjugated Annexin V (Annexin V-FITC) and propidium iodide (PI). The mRNA expression levels of CCND1, TP53, BCL2 and BAX genes were determined using Real-time Quantitative Polymerase Chain Reaction analysis. Results: The MTT assay demonstrated that treatment with QI gall extract significantly reduced the number of viable cells in the A549, BGC823, and KYSE-30 cell lines at IC50 concentrations of 440.1, 437.1, and 465.2 mg/ml, respectively. Additionally, compared to untreated cell population, the percentages of early apoptosis, late apoptosis, and necrosis in the A549, BGC823, and KYSE-30 cells significantly increased following treatment with QI gall extract (P< 0.05). Also, the treatment with QI gall extract influenced the expression of CCND1, TP53, BCL2 and BAX genes. Conclusions: The present findings indicated that the gall extract of QI can inhibit the growth of A549, BGC823, and KYSE-30 cells by inducing apoptosis, which may be mediated via mitochondria-dependent pathway.

Leveraging cfDNA fragmentomic features in a stacked ensemble model for early detection of esophageal squamous cell carcinoma.

In this study, we develop a stacked ensemble model that utilizes cell-free DNA (cfDNA) fragmentomics for the early detection of esophageal squamous cell carcinoma (ESCC). This model incorporates four distinct fragmentomics features derived from whole-genome sequencing (WGS) and advanced machine learning algorithms for robust analysis. It is validated across both an independent validation cohort and an external cohort to ensure its generalizability and effectiveness. Notably, the model maintains its robustness in low-coverage sequencing environments, demonstrating its potentials in clinical settings with limited sequencing resources. With its remarkable sensitivity and specificity, this approach promises to significantly improve the early diagnosis and management of ESCC. This study represents a substantial step forward in the application of cfDNA fragmentomics in cancer diagnostics, emphasizing the need for further research to fully establish its clinical efficacy.

Nutrition and continuous nursing intervention following radical resection of esophageal cancer in a patient after liver transplantation: a case report.

Background: Reasonable nutritional intervention is very important to promote wound healing and rehabilitation in patients with radical esophagectomy for esophageal cancer. This report aims to summarize the experience of nutritional and continuous nursing intervention in a patient who underwent radical resection of esophageal cancer after liver transplantation, by testing a comprehensive approach to optimize nursing plans in similar clinical practice. We hope that the implementation of home enteral nutrition can improve the nutrition status and quality of life of postoperative patients. Case Description: A patient with liver transplantation was admitted to The Fourth Hospital of Hebei Medical University for postoperative care. The nursing intervention were subsequently summarized and analyzed. In July 2023, the patient successfully underwent radical resection for esophageal cancer. Following the operation, the patient received regular medication and on-site nutritional intervention with the consent of her family. At discharge, the prealbumin, albumin, total protein and hemoglobin values of the patient were low, and body weight was 91 kg. The patient's nutritional risk screening (NRS2022) score was 5 points, and the Patient-Generated Subjective Global Assessment (PG-SGA) score was 4 points. After discharge, the patient continued to receive family enteral nutrition treatment, dietary guidance and psychological nursing. A follow-up review conducted 4 weeks after discharge showed improvements in the patient's NRS2022, albumin, total protein, hemoglobin, and body weight. Conclusions: Strengthening postoperative nutritional intervention are vital for promoting rehabilitation in patients who undergo radical resection of esophageal cancer after liver transplantation.

Disease burden and related risk factors of esophageal cancer in China and globally from 1990 to 2021, with forecast to 2035: An analysis and comparison.

INTRODUCTION: In this study we estimate the burden of esophageal cancer (EC) in China and globally from 1990 to 2021, with a forecast to 2035, using Global Burden of Disease (GBD) data. We also analyze the related risk factors to investigate burden trends. METHODS: Mortality, disability-adjusted life years (DALYs), crude rates, and age-standardized rates of EC were analyzed in China and globally from 1990 to 2035, utilizing GBD open data as a secondary dataset analysis of GBD data. Temporal change trends of EC risk factors were analyzed from 1990 to 2021. Joinpoint regression determined average annual percentage change (AAPC) of age-standardized rates. Descriptive analysis compared mortality and DALYs by age groups. Bayesian age-period-cohort (BAPC) predicted age-standardized mortality and DALYs rates for the next 14 years. RESULTS: The ASMR and ASDR fluctuations in EC were significant in China, showing an overall downward trend. Globally, although there was also a downward trend, the fluctuations were relatively mild. The number of deaths and DALYs related to EC in China and globally showed a significant upward trend. Age-specific burden trends in China for EC indicated that the age group with the peak number of EC deaths shifted to the 70-74 years age group in 2021, while DALYs peaked in the 65-69 years age group. The crude mortality rate (CMR) peaked consistently in 1990 and 2021, both within the 90-94 years age range, while the crude DALY rate (CDR) shifted to the 85-89 years age group. Overall, the burden of EC deaths and DALYs in the population aged <40 years was relatively low, increasing rapidly after the age of 40 years, reaching a peak and gradually declining, and reaching a lower level after the age of 85 years. The predictive results of the BAPC model indicated that over the next 14 years, both ASMR and ASDR for EC in China and globally would show a slight overall increase. The GBD 2021 study identified smoking, high alcohol use, chewing tobacco, and diet low in vegetables as the main risk factors affecting EC mortality rate and DALYs. Among these, smoking and alcohol use were the most significant risk factors, with a higher impact on EC in China compared to the global level. From 1990 to 2021, the overall changes in ASMR and ASDR indicate a decreasing trend in the impact of these four risk factors on EC mortality rate and DALYs. CONCLUSIONS: The burden of EC is expected to steadily increase in China and globally until 2035, posing a significant challenge. Targeted prevention and control policies, such as calling on people to quit smoking and reduce alcohol use, may help curb this upward trend.

PD-1 inhibitors in advanced esophageal squamous cell carcinoma: a survival analysis of reconstructed patient-level data.

Background: Recently, a sum of trials of programmed cell death-1 (PD-1) inhibitors combined with chemotherapy have shown excellent efficacy compared to chemotherapy alone in patients with previously untreated, advanced esophageal squamous cell carcinoma (ESCC). However, there is no head-to-head comparison and consensus on which immunotherapy regimen results in better survival outcomes. This study aimed to evaluate the survival efficacy of various PD-1 inhibitor-based therapies in the first-line treatments for patients with advanced ESCC. Methods: Data collected prior to 31 July 2023 were searched in the PubMed, Cochrane Library, Embase, Medline, and Web of Science databases. Overall survival (OS) and progression-free survival curves were pooled using the MetaSurv package. Survival data were compared by reconstructed individual patient data. Results: A total of 4,162 patients and seven randomized controlled trials were included. After synthesizing, PD-1 inhibitors prolonged median OS from 11.3 months (95% CI (confidence interval) 10.7-11.7) to 15.6 months (95% CI 14.7-16.3). Based on reconstructed patient-level data, the toripalimab, tislelizumab, and sintilimab group achieved the longest OS, whereas the sintilimab and tislelizumab group had the lowest risk of recurrence than other treatments. In patients with a combined positive score of ≥10, sintilimab had better OS efficacy than pembrolizumab (HR: 0.71, 95% CI: 0.52-0.96). In terms of tumor proportion score of ≥1%, camrelizumab, nivolumab, and toripalimab showed proximate survival benefits in both OS and progression-free survival. Conclusion: PD-1 inhibitor combined with chemotherapy significantly improved the survival time of patients with advanced ESCC. Toripalimab, tislelizumab, and sintilimab plus chemotherapy showed the best OS benefit. Longer progression-free benefits might be generated from adding tislelizumab and sintilimab to chemotherapy. Sintilimab was strongly recommended for patients with high programmed cell death-ligand 1 abundance. Systematic Review Registration: [https://www.crd.york.ac.uk/PROSPERO/], identifier [CRD42024501086].

Assessing the outcomes of posterior thoracic para-aortic lymph node dissection after induction chemotherapy in patients with esophageal squamous cell carcinoma.

Posterior thoracic para-aortic lymph node (TPAN) metastasis is a distant metastasis of esophageal cancer. Several case reports have shown that radical esophagectomy and lymphadenectomy for posterior TPAN improve the prognosis of patients with cStage IVB esophageal cancer and solitary posterior TPAN metastasis; however, the true value of this procedure is unclear. The primary objective of this study was to evaluate the short- and long-term outcomes of lymphadenectomy for posterior TPAN after induction chemotherapy in esophageal cancer. This study enrolled 15 patients who underwent radical esophagectomy for cStage IVB esophageal cancer with solitary posterior TPAN metastasis after induction chemotherapy between January 2013 and October 2022 at our hospital. The short- and long-term of radical esophagectomy and lymphadenectomy for posterior TPAN were retrospectively evaluated. All patients who underwent radical esophagectomy and lymphadenectomy for posterior TPAN achieved a pR0 in this study. The median operative time and intraoperative blood loss were 385 minutes and 164 ml, respectively. Four patients (26.7%) had postoperative complications of Clavien-Dindo grade II or more. The median postoperative hospital stay was 15 days. The 5-year overall survival and recurrence-free survival rates were 55.6% (95% confidence interval: 23.1-79.0) and 55.0% (95% confidence interval: 25.3-77.2), respectively. We showed that lymphadenectomy for posterior TPAN metastasis was associated with an improved prognosis of some patients with advanced esophageal cancer. This technique may serve as a viable treatment option for patients who respond well to induction chemotherapy.

Metformin suppresses esophageal cancer progression through the radiation­induced cellular senescence of cancer­associated fibroblasts.

Senescent cells are known to secrete proteins, including inflammatory cytokines and damage­associated molecular patterns. This phenomenon is known as the senescence­associated secretory phenotype (SASP). SASP in cancer stromal fibroblasts is involved in cancer growth and progression. Conversely, metformin, an antidiabetic drug, has been reported to inhibit SASP induction by inhibiting the activation of NF­κB, a regulator of SASP. To date, at least to the best of our knowledge, there have been no reports regarding cellular senescence in fibroblasts and tumor progression via the SASP­mediated paracrine pathway. The present study thus aimed to elucidate the induction mechanisms of SASP in radiation­induced fibroblasts and to determine its effects on cancer progression via the paracrine pathway. Furthermore, the present study aimed to determine whether controlling SASP using metformin suppresses cancer progression. A well­differentiated esophageal cancer cell line established by the authors' department and fibroblasts isolated and cultured from the non­cancerous esophageal mucosa of resected esophageal cancer cases were used for the experiments. Fibroblasts were irradiated with 8 Gy radiation, and the changes in the expression of the senescence markers, SA­ß­gal, p21, p16 and NF­κB were evaluated using immunofluorescent staining and western blot analysis in the presence or absence of metformin treatment. The culture supernatants of irradiated fibroblasts treated with metformin and those treated without metformin were collected and added to the cancer cells to evaluate their proliferative, invasive and migratory abilities. Vimentin and E­cadherin expression levels were also evaluated using immunofluorescent staining and western blot analysis. The expression levels of p16, p21 and NF­κB in irradiated fibroblasts were attenuated by treatment with metformin. Supernatants collected from irradiated fibroblasts exhibited the proliferative activity of esophageal cancer cells, and the promotion of migratory and invasion abilities, which may be due to epithelial­mesenchymal transition and changes in cell morphology. These reactions were confirmed to be suppressed by the addition of the supernatant of cultured fibroblasts pre­treated with metformin. On the whole, the present study demonstrates that fibroblasts in the cancer stroma may be involved in tumor progression through cellular senescence.

Thoracic Endovascular Aortic Repair for an Aortoesophageal Fistula Caused by Esophageal Cancer: A Case Report and Literature Review.

Aortoesophageal fistula (AEF) is an uncommon complication of esophageal cancer and can be extremely fatal if left untreated. Compared to open repair, thoracic endovascular aortic repair (TEVAR), a less invasive technique, is the initial recommended treatment in cases of hemorrhagic shock secondary to AEF, as this procedure showed a favorable outcome in controlling the overt bleeding. Here, we present a case of a patient with a history of stage IV esophageal cancer being treated with chemotherapy and an esophageal stent due to a previous tracheoesophageal fistula who presented to the emergency room due to severe gastroesophageal bleeding and hemorrhagic shock. A CT angiography of the chest revealed an AEF. The patient was subsequently resuscitated and treated with TEVAR. After the procedure, the hemorrhage was managed, and the patient was discharged with palliative radiation therapy. However, after one month, the patient had a major gastrointestinal hemorrhage, which caused her death. This example indicates the necessity of early detection and surgical intervention in AEF patients with unstable hemodynamics who have underlying unresectable esophageal cancer and chemotherapy. TEVAR should be conducted as soon as possible before the open surgery to achieve the best outcome for patients.

Immunotherapy Plus Chemoradiation Improves Overall Survival in Stage IV Esophageal Cancer: A Cohort Study.

Background and Aims: The association of immunotherapy in combination with radiation therapy (RT) or chemoradiation with the overall survival (OS) of patients diagnosed with stage IV esophageal cancer (EC) is unknown. The aim of the current study is to explore the association of immunotherapy with OS in patients with advanced stage EC who received chemotherapy, RT, or chemoradiation. Methods: We conducted a cohort study using the National Cancer Database and included patients diagnosed between 2013 and 2020 with stage IV esophageal adenocarcinoma or squamous cell carcinoma. The association of immunotherapy with OS was assessed with Cox proportional hazards regression, adjusted for age at diagnosis, race, sex, stage, histology, Charlson score, education, income, insurance, hospital type, place of living, region, distance to facility, year of diagnosis, and treatment modality. Results: Of 18,260 patients, 2946 (17%) received immunotherapy. In the multivariable COX analysis, patients who received immunotherapy had significantly improved OS compared with no immunotherapy (hazard ratio [HR]: 0.71; 95% confidence interval [CI]: 0.67-0.75; P < .001). Chemotherapy plus immunotherapy was associated with improved OS compared to chemotherapy alone (HR: 0.69; 95% CI: 0.64-0.75; P < .001). RT plus immunotherapy was associated with improved OS compared to RT alone (HR: 0.60; 95% CI: 0.46-0.78; P < .001). Treatment with chemoradiation plus immunotherapy was associated with significantly improved OS compared with chemoradiation alone (HR 0.78; 95% CI: 0.71-0.86; P < .001). Conclusion: The addition of immunotherapy to chemotherapy, RT, and chemoradiation was associated with improved OS compared with chemotherapy alone, RT alone, or chemoradiation alone in patients with stage IV EC.

Investigating iRHOM2-Associated Transcriptional Changes in Tylosis With Esophageal Cancer.

Background and Aims: Survival rates for esophageal squamous cell carcinoma (ESCC) are extremely low due to the late diagnosis of most cases. An understanding of the early molecular processes that lead to ESCC may facilitate opportunities for early diagnosis; however, these remain poorly defined. Tylosis with esophageal cancer (TOC) is a rare syndrome associated with a high lifetime risk of ESCC and germline mutations in RHBDF2, encoding iRhom2. Using TOC as a model of ESCC predisposition, this study aimed to identify early-stage transcriptional changes in ESCC development. Methods: Esophageal biopsies were obtained from control and TOC individuals, the latter undergoing surveillance endoscopy, and adjacent diagnostic biopsies were graded as having no dysplasia or malignancy. Bulk RNA-Seq was performed, and findings were compared with sporadic ESCC vs normal RNA-Seq datasets. Results: Multiple transcriptional changes were identified in TOC samples, relative to controls, and many were detected in ESCC. Accordingly, pathway analyses predicted an enrichment of cancer-associated processes linked to cellular proliferation and metastasis, and several transcription factors were predicted to be associated with TOC and ESCC, including negative enrichment of GRHL2. Subsequently, a filtering strategy revealed 22 genes that were significantly dysregulated in both TOC and ESCC. Moreover, Keratin 17, which was upregulated in TOC and ESCC, was also found to be overexpressed at the protein level in 'normal' TOC esophagus tissue. Conclusion: Transcriptional changes occur in TOC esophagus prior to the onset of dysplasia, many of which are associated with ESCC. These findings support the utility of TOC to help reveal the early molecular processes that lead to sporadic ESCC.

Novel co-delivery of oridonin and docetaxel nanoliposome for an enhanced antitumor effect on esophageal cancer.

INTRODUCTION: Esophageal cancer is one of the major cancers in China. Most patients with esophageal cancer are diagnosed at an advanced stage, and the 5 year survival rate is discouraging. Combined chemotherapy is a common method for the treatment of esophageal cancer. METHODS: In this study, distearoyl phosphatidyl ethanolamine polyethylene glycol 2000 (DSPE-PEG2000) nanoliposomes (NLPs) encapsulating the anticancer drugs docetaxel (DOX) and oridonin (ORD) were prepared, and their ability to enhance the release of anticancer drugs was determined. The NLP system was characterized by transmission electron microscopy, particle size and encapsulation efficiency. In addition, the release characteristics and pharmacodynamics of these drugs were also studied in detail. RESULTS: When the DOX/ORD ratio was 2:1, the higher proportion of DOX led to a stronger synergy effect. DOX/ORD NLPs were prepared by the high-pressure homogenization method and had a uniform spherical morphology. The mean particle size and polydispersity index were determined to be 246.4 and 0.163, respectively. The stability results showed that no significant change was observed in particle size, zeta potential, Encapsulation efficiency and dynamic light scattering for DOX/ORD NLPs during the observation period. The results of in vitro release illustrated that the acidic environment of tumor might be beneficial to drug release. The three-dimensional tumorsphere showed that DOX/ORD NLPs can reach the interior of tumor spheres, which destroys the structure of cells, resulting in irregular spherical tumor spheres. The in vivo study results indicated that DOX/ORD NLPs had an obvious targeting effect on subcutaneous tumors and have the potential to actively deliver drugs to tumor tissues. Terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining was used to detect apoptosis. The results showed that DOX/ORD NLP treatment could significantly induce apoptosis and inhibit tumor growth. CONCLUSION: The DOX/ORD NLPs prepared in this study can enhance the anti-tumor activity, and are expected to be a promising co-delivery platform for the treatment of esophageal cancer.

Intra-operative pyloric BOTOX injection versus pyloric surgery for prevention of delayed gastric emptying after esophagectomy.

BACKGROUND: Delayed gastric emptying (DGE) is a common complication after esophagectomy. BOTOX injections and pyloric surgeries (PS), including pyloroplasty (PP) and pyloromyotomy (PM), are performed intraoperatively as prophylaxis against DGE. This study compares the effects of pyloric BOTOX injection and PS for preventing DGE post-esophagectomy. METHODS: We retrospectively reviewed Moffitt's IRB-approved database of 1364 esophagectomies, identifying 475 patients receiving BOTOX or PS during esophageal resection. PS was further divided into PP and PM. Demographics, clinical characteristics, and postoperative outcomes were compared using Chi-Square, Fisher's exact test, Wilcoxon rank-sum, and ANOVA. Propensity-score matching was performed between BOTOX and PP cohorts. RESULTS: 238 patients received BOTOX, 108 received PP, and 129 received PM. Most BOTOX patients underwent fully minimally invasive robotic Ivor-Lewis esophagectomy (81.1% vs 1.7%) while most PS patients underwent hybrid open/Robotic Ivor-Lewis esophagectomy (95.7% vs 13.0%). Anastomotic leak (p = 0.57) and pneumonia (p = 0.75) were comparable between groups. However, PS experienced lower DGE rates (15.9% vs 9.3%; p = 0.04) while BOTOX patients had less postoperative weight loss (9.7 vs 11.45 kg; p = 0.02). After separating PP from PM, leak (p = 0.72) and pneumonia (p = 0.07) rates remained similar. However, PP patients had the lowest DGE incidence (1.9% vs 15.7% vs 15.9%; p = < 0.001) and the highest bile reflux rates (2.8% vs 0% vs 0.4%; p = 0.04). Between matched cohorts of 91 patients, PP had lower DGE rates (18.7% vs 1.1%; p = < 0.001) and less weight loss (9.8 vs 11.4 kg; p = < 0.001). Other complications were comparable (all p > 0.05). BOTOX was consistently associated with shorter LOS compared to PS (all p = < 0.001). CONCLUSION: PP demonstrates lower rates of DGE in unmatched and matched analyses. Compared to BOTOX, PS is linked to reduced DGE rates. While BOTOX is associated with more favorable LOS, this may be attributable to difference in operative approach. PP improves DGE rates after esophagectomy without improving other postoperative complications.

Preoperative quality of life predicts complications in thoracic surgery: a retrospective cohort study.

OBJECTIVES: Patients undergoing thoracic surgery experience high complication rates. It is uncertain whether preoperative health-related quality of life (HRQOL) measurements can predict patients at higher risk for postoperative complications. The objective of this study was to determine the association between preoperative HRQOL and postoperative complications among patients undergoing thoracic surgery. METHODS: This was a retrospective cohort study of prospectively collected data. Consecutive patients undergoing elective thoracic surgery at a Canadian tertiary care centre between January 2018 to January 2019 were included. Patient HRQOL was measured using the Euroqol-5 Dimension (EQ-5D) survey. Complications were recorded using the Ottawa Thoracic Morbidity and Mortality system. Uni- and multivariable analysis were performed. RESULTS: Of 515 surgeries performed, 133 (25.8%) patients experienced at least one postoperative complication. 345 (67.0%) patients underwent surgery for malignancy. A range of 271 (52.7%) to 310 (60.2%) patients experienced pain/discomfort at each timepoint. On multivariable analysis, lower preoperative EQ-5D visual analogue scale scores were significantly associated with postoperative complications [adjusted odds ratio 0.97, 95% confidence interval 0.95-0.99; p = 0.01]. Presence of malignancy was not independently associated with complications (p = 0.68). CONCLUSIONS: Self-reported preoperative HRQOL can predict incidence of postoperative complications among patients undergoing thoracic surgery. Assessments of preoperative HRQOL may help identify patients at higher risk for developing complications. These findings could be used to direct preoperative risk-mitigation strategies in areas of HRQOL where patients suffer most, such as pain. The full perioperative trajectory of patient HRQOL should be discerned to identify subsets of patients who share common risk factors.

Lipopolysaccharide induces CCL2 through TLR4 signaling and promotes esophageal squamous cell carcinoma cell proliferation.

Poor oral health is an independent risk factor for upper-aerodigestive tract cancers, including esophageal squamous cell carcinoma (ESCC). Our previous findings suggest that high expression of toll-like receptor (TLR) 4, which recognizes lipopolysaccharide (LPS) released from periodontal pathogens, correlates with a poor prognosis after esophagectomy for ESCC. We therefore hypothesized that LPS influences cancer cell proliferation and disease progression in ESCC. We used 8 ESCC cell lines to investigate how LPS affects ESCC cell proliferation and migration activity. We also assessed mRNA and protein expression to determine how LPS affects cytokine production and whether blocking TLR4 signaling attenuates that effect. We also used a mouse xenograft model to investigate whether LPS upregulates ESCC tumor progression in vivo. We then determined whether C-C motif chemokine ligand 2 (CCL2) expression in clinical samples correlates with 5-year overall survival (OS) and disease-specific survival (DSS) in ESCC patients after esophagectomy. LPS significantly upregulated cell proliferation and migration in all ESCC lines. It also upregulated CCL2 production. In vivo, subcutaneous LPS administration significantly increased ESCC tumor volume in mice. In clinical samples, high CCL2 expression significantly correlated with 5-year OS and DSS. There was also a significant correlation between CCL2 and TLR4 expression status, suggesting the involvement of an LPS-TLR4-CCL2 cascade in clinical settings. LPS significantly upregulates cell proliferation and tumor progression through an LPS-TLR4-CCL2 cascade and influences prognosis after esophagectomy for ESCC. This suggests improving the oral environment has the potential to improve the prognosis of ESCC patients after esophagectomy.