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Background Anlotinib, a tyrosine kinase inhibitor, has shown encouraging anti-tumor activity in esophageal squamous cell carcinoma (ESCC). This study was designed to assess the efficacy and safety of anlotinib plus paclitaxel and cisplatin (TP) as first-line therapy for advanced ESCC. Methods In a multi-center, single-arm, phase II clinical trial, patients (aged > 18 years) with ESCC, which was judged to be locally advanced, recurrent, or metastatic, received 10 mg oral anlotinib once daily on days 1–14, 135 mg/m2 intravenous paclitaxel on day 1, and 60–75 mg/m2 intravenous cisplatin on days 1–3 every 3 weeks for a maximum of 4–6 cycles as the initial therapy in five centers in China. Subsequently, patients received anlotinib monotherapy (10 mg) as maintenance therapy until tumor progression or intolerable toxicity. The primary endpoint was progression-free survival (PFS). Results Forty-seven patients were enrolled in this study between October 2019 and March 2021. The median follow-up was 14.04 months (IQR, 9.30–19.38). Of 46 with assessable efficacy, the median PFS and median overall survival were 8.38 months (95% CI, 6.59–10.17) and 18.53 months (95% CI, 13.11–23.95), respectively. The objective response rate was 76.1% (95% CI, 61.2–87.4%), with 4 (8.7%) complete responses and 31 (67.4%) partial responses. The disease control rate was 91.3% (95% CI, 79.2–97.6%). The median duration of response was 6.80 months (95% CI, 4.52–9.08), and 1 patient had an ongoing response for 23 months. Subgroup analysis revealed no association between clinical factors and survival or response. Of the 47 patients with assessable safety, the main grade ≥ 3 treatment-emergent adverse events (TEAEs) were neutropenia (17.0%), bone marrow suppression (12.8%), and vomiting (10.6%). No treatment-related deaths or serious TEAEs were observed. Notably, higher c-Kit levels were an independent factor for superior PFS (HR = 0.032; 95% CI, 0.002–0.606; P = 0.022). Conclusions The study demonstrated a manageable safety profile and durable clinical response of anlotinib plus TP as first-line therapy in advanced ESCC, which suggested a potential therapeutic option for this population. Trial registration ClinicalTrials.gov NCT04063683. Registered 21 August 2019.

Aim of the Study: Several studies have evaluated the correlation between xeroderma pigmentosum Group A (XPA) A23G polymorphism (rs 1800975) and esophageal cancer in Chinese people. However, the results are inconsistent. To assess the effects of XPA A23G variants on the risk for development of esophageal cancer in the Chinese population, a meta-analysis was performed. Materials and Methods: Studies were identified using PubMed and Chinese databases through December 2015. The associations were assessed with pooled odds ratios (ORs) and 95% confidence intervals (95% CIs). Results: This meta-analysis identified seven studies including 1514 esophageal cancer cases and 2120 controls. In the overall analysis, no significant association between XPA A23G polymorphism and esophageal cancer was found in the Chinese population. In the subgroup analyses by geographic area(s) and source of controls, significant results were only found in studies with hospital-based controls (GG vs. AA: OR = 0.42, 95% CI = 0.28–0.62; GG vs. AA + AG: OR = 0.55, 95% CI = 0.39–0.78; GG + AG vs. AA: OR = 0.54, 95% CI = 0.40–0.72; G vs. A: OR = 0.61, 95% CI = 0.50–0.75). Conclusions: This meta-analysis suggested that XPA A23G gene polymorphism may be one low-penetrant risk factor for esophageal cancer in Chinese individuals.

Background The interaction between tumor cells and inflammatory cells has not been systematically investigated in esophageal squamous cell carcinoma (ESCC). The aim of the present study was to evaluate whether preoperative the lymphocyte-monocyte ratio (LMR), the neutrophil-lymphocyte ratio (NLR), and the platelet-lymphocyte ratio (PLR) could predict the prognosis of ESCC patients undergoing esophagectomy. Materials and methods Records from 218 patients with histologically diagnosed ESCC who underwent attempted curative surgery from January 2007 to December 2008 were retrospectively reviewed. Besides clinicopathological prognostic factors, we evaluated the prognostic value of the LMR, the NLR, and the PLR using Kaplan-Meier curves and Cox regression models. Results The median follow-up was 38.6 months (range 3-71 months). The cut-off values of 2.57 for the LMR, 2.60 for the NLR and 244 for the PLR were chosen as optimal to discriminate between survival and death by applying receiver operating curve (ROC) analysis. Kaplan-Meier survival analysis of patients with low preoperative LMR demonstrated a significant worse prognosis for DFS (p=0.004) and OS (p=0.002) than those with high preoperative LMR. The high NLR cohort had lower DFS (p=0.004) and OS (p=0.011). Marginally reduced DFS (p=0.068) and lower OS (p=0.039) were found in the high PLR cohort. On multivariate analysis, only preoperative LMR was an independent prognostic factor for both DFS (p=0.009, HR=1.639, 95% CI 1.129-2.381) and OS (p=0.004, HR=1.759, 95% CI 1.201-2.576) in ESCC patients. Conclusions Preoperative LMR better predicts cancer survival compared with the cellular components of systemic inflammation in patients with ESCC undergoing esophagectomy.

Hepatoma-derived growth factor (HDGF) is a novel jack-of-all-trades in cancer. Here we quantify the prognostic impact of this biomarker and assess how consistent is its expression in solid tumors. A comprehensive search strategy was used to search relevant literature updated on October 3, 2014 in PubMed, EMBASE and WEB of Science. Correlations between HDGF expression and clinicopathological features or cancer prognosis was analyzed. All pooled HRs or ORs were derived from random-effects models. Twenty-six studies, primarily in Eastern Asia, covering 2,803 patients were included in the analysis, all of them published during the past decade. We found that HDGF overexpression was significantly associated with overall survival (OS) (HROS=2.35, 95%CI=2.04-2.71, p

Background: The relationship between body mass index(BMI) and outcomes after chemoradiotherapy(CRT) has not been systematically addressed. The purpose of this study was to evaluate the effect of BMI on survival in patients with esophageal squamous cell carcinoma (ESCC). Materials and Methods: Sixty ESCC cases were retrospectively reviewed in this study. Patient overall survival(OS) and disease-free survival (DFS) were compared between two groups (BMI

Background: The tumor-stroma ratio (TSR) has been identified as a new and practicable prognostic histological characteristic of solid tumors. The aim of this study was to evaluate the prognostic value of the TSR in nasopharyngeal cancer (NPC). Patients and Methods: A total of 93 patients who presented with NPC from 2004 to 2007 were studied. Radiotherapy with or without chemotherapy was administered according to their Union for International Cancer Control (UICC) stages. The TSR was assessed visually on hematoxylin and eosin-stained tissue sections of biopsy specimens by 2 independent observers. Results: The 5-year overall survival (OS) and disease-free survival (DFS) rates were 66.67% and 54.91%, respectively, in the stroma-poor group and 40.48% and 33.33%, respectively, in the stroma-rich group. Both the 5-year OS and DFS rates in the stroma-poor group were significantly better than those in the stroma-rich group (p < 0.05). In a multivariate analysis, the TSR was identified as a highly significant prognostic factor for the 5-year OS (hazard ratio (HR) 1.999; p = 0.030) and the 5-year DFS (HR 1.925; p = 0.042). Conclusion: Stroma-rich tumors were associated with poor prognosis and an increased risk of relapse, which may serve as a new prognostic histological characteristic in NPC.

AIM: To compare the outcomes of pediatric patients weighing less than or more than 10 kg who underwent liver transplantation. METHODS: Data for 196 pediatric patients who underwent living donor liver transplantation between June 1994 and February 2011 were reviewed retrospectively. The information for each patient was anonymized and de-identified before analysis. The data included information regarding the pre-transplant conditions, intraoperative fluid replacement and outcomes for each patient. The 196 patients were divided into two groups: those with body weights of less than 10 kg were included in group 1 (G1; n = 101), while those with body weights of more than 10 kg were included in group 2 (G2; n = 95). For each group, the patients’ ages, body weights, heights, pediatric end stage liver disease scores, anesthesia times, and warm and cold ischemic times were analyzed. In addition, between-group comparisons were also made. Mann-Whitney U tests were used to compare all the variables except for complications and survival rates, which were analyzed using χ2 tests and Kaplan-Meier tests, respectively. RESULTS: The general medical conditions of the G1 patients were worse than those of the G2 patients, as shown by the higher pediatric end stage liver disease scores and poorer Z-scores. In addition, the pre-operative Hb and serum albumin levels were all lower for the G1 patients than for the G2 patients. The G1 patients also had significantly more intraoperative blood loss than the G2 patients. In addition, the intraoperative fluid requirements for the G1 patients, including leukocyte poor red blood cell transfusions, 5% albumin infusions and crystalloid infusions, were significantly higher than those for the G2 patients. The risk of intraoperative portal vein thrombosis was higher for the patients in G1 than for those in G2. However, the one-year survival rates (95.9% and 96.8% for G1 and G2, respectively) and three-year survival rates (94.9% and 94.6% for G1 and G2, respectively) for both groups were similar. CONCLUSION: Patients weighing less than 10 kg typically have poorer conditions, but their survival rates are comparable to those of children weighing more than 10 kg.

Microtubule-associated protein light chain 3 (LC3) is a key mediator bridging autophagy, apoptosis and differentiation. However, its role and clinical significance in resectable esophageal squamous cell carcinoma (ESCC) is still scanty. The purpose of this study was to investigate the clinical significance of LC3 by immunohistochemistry in a group of patients with ESCC treated with surgical resection. Tissue microarray that included 253 surgically resected ESCC specimens was successfully generated for immunohistochemical evaluation. The clinical/prognostic significance of LC3 expression was analyzed statistically. The association of LC3 expression with the ESCC survival rate was assessed by Kaplan-Meier and Cox proportional-hazards regression. The results showed that the immunostaining of LC3 was distributed in cytoplasm and plasma-membrane. Significantly high LC3 expression was found in ESCC cells compared with that of normal esophageal epithelial cells. Patients with low expression of LC3 demonstrated higher overall survival compared with those with high expression of LC3 (mean of 71.1 months versus 55.5 months, P = 0.022). A similar result was observed for disease-free survival (mean of 68.7 months versus 51.8 months, P = 0.021). In subgroup analysis, LC3 expression could stratify pN0 patients with ESCC. Multivariate analysis showed that the level of LC3 expression was an independent prognostic factor in ESCC (RR = 1.407, P = 0.049). This paper shows high level of LC3 suggests poor prognosis for resectable ESCC patients.

Our purpose was to compare the clinical features and prognosis of pancreatic head cancer with that of other periampullary cancers.The medical records of 82 patients (mean age of 61.67±10.52 years) with ductal adenocarcinoma of the head of pancreas and 73 patients (mean age of 60.52±11.72 years) with other periampullary adenocarcinomas, all of whom had received radical surgery, were retrospectively analyzed.There were no significant differences in age and gender between the groups (both, p0.05). However, there were significant differences in lymph node metastasis, TNM stage, clear surgical margins, tumor size, and neural invasion between the 2 groups (all p0.05). Patients with pancreatic head adenocarcinoma had significantly higher red blood cell (RBC) count and hemoglobin (Hb), albumin and pre-albumin levels, and higher platelet and white blood cell (WBC) counts than the patients with other periampullary adenocarcinomas (all p0.05). No differences in carcinoembryonic antigen (CEA) or CA19-9 were noted between the groups. The 1-year survival rates were not different between the groups (p=0.299).Pancreatic head carcinoma has different clinical manifestations and biological features than other periampullary cancers.

Radiation induced lung toxicity (RILT) is the main adverse effect in the radiation therapy of lung cancer. However, the optimal management of RILT has not been defined. In this paper, we investigated the effects of rhubarb extract on RILT, pulmonary function (PF), transforming growth factor-beta-1 (TGF-beta1), and interleukin-6 (IL-6) in lung cancer patients treated with radiotherapy.We conducted a randomized, double-blind, placebo-controlled trial. Eighty consecutive patients were randomly enrolled into two groups: trial group and control group. The trial group received three-dimensional conformal radiation therapy (3D-CRT) plus rhubarb (at a dose of 20 mg kg(-1) once a day) for 6 weeks. The control group received 3D-CRT plus a placebo containing starch for 6 weeks. Plasma TGF-beta1 and serum IL-6 were measured in all patients before, every 2 weeks during, and at 6 weeks after the completion of the treatment. RILT and PF were evaluated at 6 weeks and 6 months after the end of the treatment, respectively. The differences of TGF-beta1, IL-6, RILT, and PF between the two groups were analysed.The incidence of RILT in the trial group was significantly lower than that in the control group at 6 weeks and 6 months after treatment (32.4% versus 56.7% at week 6, and 27.0% versus 52.8% at month 6, both P0.05). The plasma TGF-beta1 levels in the trial group were significantly lower than that in the control group during and after the treatment (P0.05 or 0.01, respectively). The serum IL-6 levels in the trial group were significantly lower than that in the control group during the treatment (all P0.01). The forced vital capacity (FVC), forced expiratory volume at 1s (FEV1) at 6 weeks and the diffusion capacity for carbon monoxide (DLCO) at 6 months in the trial group were significantly improved compared to the control group (P0.05 or 0.01, respectively).The rhubarb extract significantly attenuated RILT and improved PF, probably by decreasing the level of TGF-beta1 and IL-6. These results may be of value for the prophylaxis of RILT, but the exact mechanisms underlying these prophylactic effects remain to be further explored.

To investigate the effect on apoptosis of HeLa cells by transfecting c-myc antisense oligonucleotides and seek a new method to enhance radiosensitivity of tumor cells.Immunohistochemistry staining and RT-PCR were conducted to identify the effect of ASODN. Giemsa staining, flow cytometry (FCM) and DNA ladder were performed to detect the apoptosis of HeLa cells.After transfection of ASODN (c-myc), the levels of both c-myc mRNA and C-MYC protein expression were reduced (P0.05). Giemsa staining demonstrated apoptosis-bodies on the c-myc ASODN-transfected cells. DNA ladder presented the typical ladder of apoptosis. The apoptosis rate of HeLa cells transfected with c-myc ASODN was (10.29 +/- 0.66)%, transfected c-myc ASODN combined irradiation was (16.83 +/- 0.57)%, which were much higher than that of control group (1.79 +/- 0.19)% (P0.05).The c-myc ASODN could effectively down-regulate the expression of c-myc; furthermore, transfection of c-myc ASODN could more effectively induce apoptosis of HeLa cells which subsequently enhanced radiosensitivity of HeLa cells.

The purpose of this study was to determine the serum vascular endothelial growth factor (VEGF) level before and after radiotherapy in the nasopharyngeal carcinoma.In this study we used the methods of ELISA to test the serum VEGF level of 66 cases which including 46 cases of nasopharyngeal carcinoma and 20 cases of healthy controls.The serum VEGF levels in nasopharyngeal carcinoma patients were significantly higher than those of healthy controls (P0.01). The serum levels of VEGF were significantly reduced at the end of radiotherapy (P0.01). The recurrence or metastasis rate was significantly higher in cases with150 ng/L VEGF level than those with150 ng/L.VEGF plays an important role in the growth and prognosis of nasopharyngeal carcinoma.

AIM: To investigate the association between nuclear β-catenin overexpression in rectal adenocarcinoma and radioresistance. METHODS: A retrospective analysis was conducted. The analysis involved 136 patients with locally advanced rectal adenocarcinoma who underwent short-course preoperative radiotherapy and radical resection. The expression of β-catenin in both pretreatment biopsy specimens and resected primary tumor tissues was examined by immunohistochemistry. The correlation of β-catenin expression with radioresistance was evaluated using the tumor regression grading (TRG) system. The relationship between β-catenin expression and clinicopathological characteristics was also analyzed. Univariate and logistic multivariate regression analyses were adopted to determine the independent factors of radioresistance. RESULTS: Nuclear β-catenin overexpression was more evident in radioresistant rectal adenocarcinoma than in radiosensitive rectal adenocarcinoma (57.6% vs 16.7%, P < 0.001). Nuclear β-catenin was overexpressed in favor of poor TRG (≤ 2), whereas membrane β-catenin was expressed in favor of good TRG (≥ 3). Nuclear β-catenin expression in tumor cell differentiation (P = 0.018), lymph node metastasis (P = 0.022), and TRG (P < 0.001) showed significant differences. Univariate analyses demonstrated that radioresistance is associated with nuclear β-catenin overexpression (P < 0.001). In addition, logistic multivariate regression analysis indicated that only three factors, namely, tumor size (P < 0.001), tumor cell differentiation (P < 0.001), and nuclear β-catenin overexpression (P < 0.001), are associated with radioresistance. By using radioresistance as a prediction target, nuclear β-catenin-based prediction alone achieved 83% accuracy, 65% sensitivity, and 88% specificity. CONCLUSION: Nuclear β-catenin overexpression may be a valuable candidate to predict the response of rectal adenocarcinoma to preoperative radiotherapy.