Bone metastasis of esophageal carcinoma diagnosed as a first primary tumor: a population-based study.

Background: This study aimed to explore predictors of bone metastasis (BM) of esophageal carcinoma (EC) and factors affecting the prognosis of EC with BM (ECBM). Methods: We retrospectively studied the data of EC patients from the Surveillance, Epidemiology, and End Results (SEER) database between 2010 and 2016. Logistic regression analysis was used to analyze the risk factors of BM. Cox regression and Fine and Gray's competing risk regression were performed to identify prognostic factors associated with all-cause and cancer-specific death, respectively. The Kaplan-Meier method was used to assess survival. Results: After exclusion, 8,916 patients were eligible, of whom 462 (5.2%) had ECBM. Independent risk factors of BM were age <65 years, male sex, stage T1, advanced N stage, and non-bone organ metastases. For EC, the median survival time (MST) was 17 months, and the 3- and 5-year survival rates were 31.6% and 23.3%, respectively; meanwhile, for BM, the MST was 5 months, and the 3- and 5-year survival rates were 2% and 1%, respectively. Adenocarcinoma, stage T2, the absence of non-bone organ metastases, and combined radiotherapy and chemotherapy were associated with a reduced risk of all-cause death in ECBM patients. Stage T2, the absence of non-bone organ metastases, and combined radiotherapy and chemotherapy were associated with a decreased risk of cancer-specific death in ECBM patients. Conclusions: Although rare, BM severely impairs the prognosis of EC. BM predictors and factors influencing the prognosis of ECBM may help distinguish high-risk patients with BM and assess survival in ECBM patients.

A safe and effective anastomotic technique for robot-assisted minimally invasive oesophagectomy: Reverse-puncture anastomosis.

BACKGROUND: Oesophagogastric anastomosis is mainly complicated by its tediousness. We hope to modify an oesophagogastric anastomotic technique that simplifies anastomosis. METHODS: We conducted a retrospective analysis of 57 cases executed using reverse-puncture anastomotic (RPA) technique and 64 cases of manual purse anastomosis (MPA) technique for robot-assisted minimally invasive oesophagectomy (RAMIE). Baseline characteristics and perioperative outcomes were analysed. RESULTS: There were no significant differences between the 2 groups with regards to demographic data and clinical features. All patients had R0 resection. Relative to MPA, RPA group experienced significantly shorter operation times (232.5 ± 33.84 min vs. 262.3 ± 83.94 min, p = 0.038).RPA group patients had shorter anastomotic times relative to MPA group patients (10.5 ± 3.4 min vs. 18.3 ± 4.1 min, p = 0.014). No adverse events were observed. CONCLUSIONS: Reverse-puncture anastomosis is safe, feasible in RAMIE. This approach has the potential to efficiently shorten the anastomotic time and ensure safe operation.

Risk prediction nomogram for major morbidity related to primary resection for esophageal squamous cancer.

BACKGROUND AND OBJECTIVES: Postoperative major complications after esophageal cancer resection vary and may significantly impact long-term outcomes. This study aimed to build an individualized nomogram to predict post-esophagectomy major morbidity. METHODS: This retrospective study included 599 consecutive patients treated at a single center between January 2017 and April 2019. Of them, 420 and 179 were assigned to the model development and validation cohorts, respectively. Major morbidity predictors were identified using multiple logistic regression. Model discrimination and calibration were evaluated by validation. Regarding clinical usefulness, we examined the net benefit using decision curve analysis. RESULTS: The mean age was 64 years; 79% of the patients were male. The most common comorbidities were hypertension, diabetes mellitus, and stroke history. The 30-day postoperative major morbidity rate was 24%. Multivariate logistic regression analysis showed that age, smoking history, coronary heart disease, dysphagia, body mass index, operation time, and tumor size were independent risk factors for surgery-associated major morbidity. Areas under the receiver-operating characteristic curves of the development and validation groups were 0.775 (95% confidence interval, 0.721-0.829) and 0.792 (95% confidence interval, 0.709-0.874), respectively. In the validation cohort, the nomogram showed good calibration. Decision curve analysis demonstrated that the prediction nomogram was clinically useful. CONCLUSION: Morbidity models and nomograms incorporating clinical and surgical data can be used to predict operative risk for esophagectomy and provide appropriate resources for the postoperative management of high-risk patients.

An artificial neural network model predicting pathologic nodal metastases in clinical stage I-II esophageal squamous cell carcinoma patients.

BACKGROUND: Current preoperative staging for lymph nodal status remains inaccurate. The purpose of this study was to build an artificial neural network (ANN) model to predict pathologic nodal involvement in clinical stage I-II esophageal squamous cell carcinoma (ESCC) patients and then validated the performance of the model. METHODS: A total of 523 patients (training set: 350; test set: 173) with clinical staging I-II ESCC who underwent esophagectomy and reconstruction were enrolled in this study. Their post-surgical pathological results were assessed and analysed. An ANN model was established for predicting pathologic nodal positive patients in the training set, which was validated in the test set. A receiver operating characteristic (ROC) curve was also created to illustrate the performance of the predictive model. RESULTS: Of the enrolled 523 patients with ESCC, 41.3% of the patients were confirmed pathologic nodal positive (216/523). The ANN staging system identified the tumour invasion depth, tumour length, dysphagia, tumour differentiation and lymphovascular invasion (LVI) as predictors for pathologic lymph node metastases. The C-index for the ANN model verified in the test set was 0.852, which demonstrated that the ANN model had a good predictive performance. CONCLUSIONS: The ANN model presented good performance for predicting pathologic lymph node metastasis and added indicators not included in current staging criteria and might help improve the staging strategies.

Comparison of Two Different Natural Oil Body Emulsions: in vitro Gastrointestinal Digestion.

The surface compositions and structure of oil bodies (OBs) are dependent on the oil crop, and these factors affect in vitro gastrointestinal digestion behaviors. Herein, a comparative study was conducted to examine the in vitro gastrointestinal digestion characteristics of two natural emulsions prepared with soybean seeds and rapeseed OBs during gastrointestinal digestion process. The average particle size of soybean OBs and rapeseed OBs emulsions was 0.46 and 5.02 µm, respectively. The droplet size of soybean seed and rapeseed OBs emulsions was large with relatively low zeta-potentials at 30 min digestion time in simulated gastric fluid condition. The droplet size of two natural OBs emulsions decreased with increasing digestion time in simulated gastric fluid condition. The average droplet size of both emulsions gradually decreased with increasing digestion time in simulated intestinal fluid conditions. The zeta-potential of the two emulsions increased with increasing digestion time in simulated intestinal fluid conditions. The extent of free fatty acids of soybean OBs emulsions was significantly higher than rapeseed after 20 min digestion time in simulated intestinal fluid conditions. The obtained results suggested that plant OBs could be useful as natural emulsifiers in the development of functional food and achieve controlled release of bioactive compounds from emulsions during gastrointestinal digestion.

A novel role of IGFBP7 in mouse uterus: regulating uterine receptivity through Th1/Th2 lymphocyte balance and decidualization.

Previously we have screened out Insulin-like Growth Factor Binding Protein 7 (IGFBP7) as a differentially expressed gene in post-implantation uterus versus pre-implantation uterus by suppressive subtractive hybridation. However its function in uterus was not clearly identified. In this research, the expression and function of IGFBP7 during post-implantation were studied. We found that IGFBP7 was mainly located in the glandular epithelium and the stroma, and was upregulated after embryo implantation. The vector pCR3.1-IGFBP7-t expressing partial IGFBP7 was constructed. Inhibition of IGFBP7 by specific DNA immunization induced significant reduction of implanted embryos and pregnancy rate. The number of implanted embryos (5.68 ± 0.46) was significantly reduced after immunization with pCR3.1-IGFBP7-t, as compared with that of the mice immunized with the control vector (12.29 ± 0.36) or saline (14.58 ± 0.40) (p<0.01). After specific inhibition of IGFBP7, the T helper type 1 (Th1) cytokine IFNγ, was significantly elevated (p<0.05) and the Th2 cytokines IL-4 and IL-10, were reduced in uteri (p<0.05). The increase of Tbet and the decrease of Gata3 were found in mice peripheral lymphocytes by flow cytometry. The expression of decidualization marker IGFBP1 and angiogenesis regulator VEGF were declined in uteri (p<0.05). The expression of apoptosis-associated proteins, caspase3 and Bcl-2, were also declined (p<0.05). These results showed that inhibition of IGFBP7 induced pregnancy failure by shifting uterine cytokines to Th1 type dominance and repressing uterine decidualization.

The antitumor immunopreventive effects of a DNA vaccine against CYP26a1 on mouse breast carcinoma.

BACKGROUND: CYP26a1, which functioned mainly as a retinoic acid (RA) catabolic enzyme, has been shown to be oncogenic and to support cell survival in many breast carcinoma cells. OBJECTIVES: The purpose of the study was to investigate the antitumor effect of a DNA vaccine targeting CYP26a1 on breast tumors development in mice which highly express CYP26a1 and to further clarify its potential mechanism. METHODS: After three times immunization of the DNA vaccine, the BALB/c mice were inoculated with the engineered 4T1 breast cancer cells expressing CYP26a1. Primary tumors were measured every 4 days after tumor cell inoculation. The primary tumors were surgically removed and weighted after 30 days of inoculation. The anti-CYP26a1 antibody titer of the antiserum was measured by an enzyme-linked immunosorbent assay (ELISA). The effect of the vaccine on apoptosis of the primary tumor was determined by terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL). Apoptosis-related proteins in primary tumor were detected by Western blotting. The expression of the Th1 and Th2 type cytokines was detected by RT-PCR. RESULTS: The vaccine could elicit the production of anti-CYP26a1 antibody and significantly inhibit the growth of the primary tumor compared to the control groups (p<0.05). The vaccine induced the apoptosis of the primary tumor with the increase in expression of apoptosis-related proteins p53, Caspase3 and Fas. Furthermore, the vaccine increased the expression of the Th1 cytokine, but not the expression of Th2 cytokine. CONCLUSION: Our study shows that the vaccine targeting CYP26a1 significantly inhibits the primary tumor growth and progression by activating the apoptosis pathway and by eliciting both humoral and cellular immune responses.

Role of secretory protease inhibitor SPINK3 in mouse uterus during early pregnancy.

Successful embryo implantation depends on intricate epithelial-stromal cross-talk. However, molecular modulators involved in this cellular communication remain poorly elucidated. Using multiple approaches, we have investigated the spatiotemporal expression and regulation of serine protease inhibitor Kazal type 3 (SPINK3) in mouse uterus during the estrous cycle and early pregnancy. In cycling mice, both SPINK3 mRNA and protein are only expressed during proestrus. In the pregnant mouse, the expression levels of both SPINK3 mRNA and protein increase on days 5-8 and then decline. Spink3 mRNA is expressed exclusively in the uterine glandular epithelium, whereas SPINK3 protein is localized on the surface of both luminal and glandular epithelium and in the decidua. Moreover, SPINK3 in the decidua has been observed in the primary decidual zone on day 6 and the secondary decidual zone on days 7-8; this is tightly associated with the progression of decidualization. SPINK3 has also been found in decidual cells of the artificially decidualized uterine horn but not control horn, whereas Spink3 mRNA localizes in the glands of both horns. The expression of endometrial Spink3 is not regulated by the blastocyst according to its expression pattern during pseudopregnancy and delayed implantation but is induced by progesterone and further augmented by a combination of progesterone and estrogen in ovariectomized mice. Thus, uterine-gland-derived SPINK3, as a new paracrine modulator, might play an important role in embryo implantation through its influence on stromal decidualization in mice.