Elective nodal irradiation versus involved-field irradiation for stage II-IV cervical esophageal squamous cell carcinoma patients undergoing definitive concurrent chemoradiotherapy: a retrospective propensity study with 8-year survival outcomes.

BACKGROUND: Definitive concurrent chemoradiotherapy (dCCRT) is suggested as the standard treatment for cervical esophageal squamous cell carcinoma (CESCC). This retrospective propensity study compared the 8-year survival outcomes and acute treatment toxicities of these patients treated with elective nodal irradiation (ENI) versus involved-field irradiation (IFI). MATERIALS AND METHODS: Patients with stage II-IV CESCC treated with dCCRT at the Fourth Hospital of Hebei Medical University between January 1, 2007 and December 31, 2020 were enrolled in the study. All the patients were restaged according to the American Joint Commission 8th edition criteria. The propensity score matching (PSM) was used to minimize the effects of treatment selection bias and potential confounding factors including sex, age, ECOG score, clinical T stage, clinical N stage, clinical TNM stage and radiation dose between the ENI group and IFI group. Survival and the prognostic factors were evaluated. RESULTS: The 131 eligible patients underwent ENI (60 patients, 45.8%) or IFI (71 patients, 54.2%). The median follow-up time was 91.1 months (range, 23.8-182.0 months) for all the patients. The median OS, 1-, 3-, 5-, and 8-year OS rates were 44.4 months, 87.8%, 55.1%, 38.3%, and 27.2%, respectively. After PSM, there were 49 patients in each group. The median OS, 1-, 3-, 5-, and 8-year OS rates for ENI and IFI group were 32.0 months, 83.7%, 48.5%, 38.5% and 31.1% versus 45.2 months, 89.8%, 52.5%, 37.5%, 26.1%, respectively (P = 0.966; HR 0.99, 95% CI 0.61-1.61). Similar locoregional control was obtained in both groups. The tendency of leukocytopenia and neutropenia was higher in ENI than in IFI (59.2% vs. 38.8%; P = 0.068 and 30.6% vs. 14.3%; P = 0.089) at the end of dCCRT. CONCLUSION: Cervical esophageal squamous cell carcinoma patients undergoing definitive concurrent chemoradiotherapy has a satisfactory prognosis with organ conservation. The involved-field irradiation might be a better alternative owing to similar overall survival outcomes and local control with less toxicity of myelosuppression.

Case Report: Intervention of radiotherapy improves the prognosis of rectal squamous cell carcinoma with high PD-L1 expression and enable patients to obtain NED status.

Background: Rectal squamous cell carcinoma (RSCC) is a rare malignancy of the rectal tumor. Due to its extremely low incidence, there is still a lack of high-level treatment evidence and clinical consensus on this disease. Case report: In this article, we report a treatment process of RSCC with high PD-L1 expression. Firstly, this patient received 2 cycles of Pembrolizumab immunotherapy, but the efficacy was less sanguine. Subsequently, 4 cycles of mFOLFOX6 chemotherapy were synchronously performed on the basis of the initial regimen. Although partial remission was achieved in the lymph nodes thereafter, the changes in the primary lesions were still not significant. After that, the patient received radiotherapy, and followed by 6 cycles of PC (Albumin-binding Paclitaxel and Nedaplatin) regimen chemotherapy combined with Pembrolizumab. Eventually, the patient achieved no evidence of disease (NED) status, and no signs of recurrence or metastasis were found after 12 months of follow-up. Conclusion: This is the first report of a RSCC patient with high PD-L1 expression achieving a complete response. Looking back over the whole treatment process of this patient, we found that the participation of radiotherapy was the inflection point of prominent efficacy, which may provide a new idea for the selection of comprehensive treatment strategies for patients with RSCC.

Assessing the predictive value of clinical factors to pathological complete response for locally advanced rectal cancer: An analysis of 124 patients.

Purpose: To investigate the clinical factors affecting pathological complete response (pCR) after neoadjuvant chemoradiotherapy (nCRT) in locally advanced rectal cancer (LARC). Methods: Clinical data of 124 LARC patients treated with nCRT and surgery in the fourth Hospital of Hebei Medical University from 2014 to 2019 were retrospectively analyzed. In this study, univariate analysis and logistic dichotomous multivariate regression analysis were used to study the clinical factors affecting pCR, and the receiver operator characteristic curve (ROC) analysis was used to further verify the accuracy of partial indexes in predicting pCR. Results: Of the 124 enrolled patients, 19 patients (15.32%) achieved pCR. Univariate analysis showed that the number of cycles of consolidation chemotherapy, serum carcino-embryonic antigen (CEA) level before treatment, MRI longitudinal length of tumor, and extramural vascular invasion (EMVI) were statistically correlated with pCR. ROC analysis of the longitudinal length of tumor measured by MRI showed that the area under the curve (AUC) value, sensitivity and specificity were 0.735, 89.47% and 48.57% respectively, and the optimal cut-off value was 5.5cm. The ROC analysis showed that the AUC value, sensitivity and specificity of pCR prediction using CEA were 0.741, 63.16% and 90.48%, respectively, and the optimal cut-off value was 3.1ng/ml. Multivariate results showed that the number of cycles of consolidation chemotherapy, serum CEA level before treatment, and EMVI were independent predictors of pCR. Conclusion: The number of cycles of consolidation chemotherapy, serum CEA level before treatment, and EMVI may be important determinants of LARC patients to reach pCR after nCRT.

Could intracranial tumor volume predict prognosis of patients with brain metastases from esophageal carcinoma?

PURPOSE: A previous study demonstrated that intracranial tumor volume had some correlation with gastrointestinal cancer patients' outcome. The aim of this study was to analyze patients with esophageal carcinoma (EC) and brain metastases to investigate if intracranial tumor volume would be a predictor of these patients' survival. METHODS: A total of 52 patients with brain metastases from esophageal squamous cell carcinoma or esophageal adenocarcinoma were retrospectively reviewed. Patients without images of brain metastases in the hospital information system were eliminated. RESULTS: The median follow-up time duration was 8.4 months (interquartile range 4.0-15.2). The median overall survival (OS) from time of brain metastases diagnosis was 8.0 months for all cases. Median OS of patients with small and large cumulative intracranial tumor volume (CITV) (<6.65 cm3 , ≥6.65 cm3 ) was 11.23 and 7.4 months, respectively. Median OS of patients with large and small largest intracranial tumor volume (LITV) (≥7.75 cm3 , <7.75 cm3 ) was 6.4 and 10.6 months, respectively. Univariate analysis demonstrated that CITV (hazard ratio [HR] 1.255, 95% confidence interval [CI] 0.673-2.342, p = 0.475) or LITV (HR 1.037, 95% CI 0.570-1.887, p = 0.904) was not significantly associated with improved OS. Multivariate analysis demonstrated that CITV and LITV were not significantly associated with improved OS. CONCLUSION: EC patients with small intracranial tumor volume may have longer OS than those with large intracranial tumor volume, but this difference did not reach statistical difference. Future studies with a larger sample size may validate the correlation of intracranial tumor volume and patient survival.

The reduction of 18F-FDG uptake ability of tumor tissue after neoadjuvant chemoradiotherapy in locally advanced rectal cancer can effectively reflect the degree of tumor regression.

Introduction: To evaluate the predictive value of 18F-fluorodeoxyglucose positron emission tomography-computed tomography (18F-FDG PET-CT) imaging parameters for the response to neoadjuvant chemoradiotherapy (nCRT) in locally advanced rectal cancer (LARC). Methods: From January 2016 to March 2020, 52 LARC patients who underwent 18F-FDG PET-CT scans within 1 week before and 8-9 weeks after nCRT, were enrolled in this study according to a pre-designed screening criteria. After total mesorectal excision (TME) surgery, we assessed tumor response to treatment and analyzed the correlation between imaging parameters obtained from two PET-CT scans and tumor regression status. Results: Tumor response assessment showed that 13 of 52 patients received good response (GR), including 9 cases with pathological complete regression (pCR) and 4 cases with near-pathological complete regression (near-pCR). We also found that the maximum standard uptake value after nCRT (post-SUVmax), the response index (RI), the mean standard uptake values after nCRT (post-SUVmean), and the ratio of tumor SUVmean to liver SUVmean after nCRT (post-Ratio), were correlated with GR and pCR. Among these parameters, post-SUVmax and RI had a near-strong correlation with pCR (rs= -0.58 and 0.59, respectively), and also had a strong correlation with GR (rs = -0.7 and 0.63, respectively). Further ROC analysis showed that post-SUVmax and RI had higher values in predicting whether patients could achieve GR and pCR after nCRT, and the area under the curve (AUC) of both were greater than 0.9. The positive predictive values (PPVs) and negative predictive values (NPVs) of post-SUVmax for GR were 80.01% and 97.3%, and for pCR were 66.68% and 97.5%, respectively. The PPVs and NPVs of the RI values for GR were 84.61% and 94.87%, and for pCR were 69.24% and 100%, respectively. Conclusion: For LARC patients, the analysis of imaging parameters such as post-SUVmax and RI, which can reflect the changes of 18F-FDG uptake capacity of tumor tissues before and after nCRT, is of great value for predicting the response of patients to neoadjuvant therapy and guiding the selection of subsequent treatment strategies.

Are People With Blood Group O More Susceptible to Nasopharyngeal Carcinoma and Have Worse Survival Rates? A Systematic Review and Meta-Analysis.

OBJECTIVE: Nasopharyngeal carcinoma (NPC) is a common malignant tumour in Southeast Asia, especially in southern China. ABO blood groups have been proven to play an important role in many cancers. However, it is still controversial whether the ABO blood group has a definite relationship to susceptibility to NPC and the prognosis of NPC patients. This meta-analysis was performed to elucidate the correlation between ABO blood group and NPC to provide more data for clinical practice. METHODS: A systematic search was performed of the Chinese National Knowledge Infrastructure (CNKI), Wanfang, Web of Science, EMBASE, and PubMed databases up to December 31, 2020. Stata 11.0 statistical software was used for this meta-analysis. RESULTS: According to the inclusion and exclusion criteria, a total of 6 studies including 6938 patients with NPC were selected. Blood group O was relevant to Chinese NPC patients, and patients with blood group O had a significantly lower incidence of NPC, while blood group A had no correlation with susceptibility to NPC. There was no difference in the 3-year overall survival (OS), locoregional relapse-free survival (LRRFS) or distant metastasis-free survival (DMFS) rates between patients with blood group O and those with non-O blood groups; worse 5-year OS, LRRFS and DMFS rates were found in patients with blood group O, whereas blood group A was not related to prognosis. CONCLUSION: Blood group O in Chinese patients with NPC seems to be a protective factor for morbidity. However, once patients with blood group O are diagnosed with NPC, this blood group often indicates unfavourable OS, LRRFS and DMFS rates. It is recommended that more attention should be paid to the influence of blood group factor on patients in the treatment of NPC.

Clinicopathological characteristics and prognosis of brain metastases in elderly patients with esophageal carcinoma.

BACKGROUND: Brain metastases (BM) from esophageal carcinoma (EC) is clinically rare and has not yet been reported in elderly patients. This study aimed to investigate the clinicopathological characteristics, outcomes and prognostic factors of BM in elderly patients with EC, in order to provide guidance for clinical practice. METHODS: A total of 20 EC patients older than 65 years who were diagnosed with BM were identified from the fourth Hospital of Hebei Medical University between January 1, 2009 and December 31, 2018. Survival was evaluated by the Kaplan-Meier method and Cox proportional hazards models. RESULTS: The median time from diagnosis of EC to BM was 11.8 months (0-249.2 months). The median overall survival (OS) was 4.8 months (1.13-23.3 months), with 20% of patients achieving the 1-year survival rate. Patients with KPS score of ≥70 had a significantly better OS than those with KPS score<70 (8.4 vs. 3.9 months, p = 0.033). Compared to patients without brain radiotherapy, patients with brain radiotherapy showed better outcomes in both median OS (8.4 vs. 2.9 months) and 1-year survival rate (23.1% vs. 14.3%, p = 0.043). The median OS of patients with radiotherapy combined with chemotherapy and/or targeted therapy and radiotherapy alone was 9.7 months (3.4-23.3 months) and 7.2 months (1.7-18.4 months), respectively, with no significant difference between the two groups (p = 0.215). CONCLUSIONS: Brain radiotherapy provided clinically meaningful survival benefit for elderly patients with BM from EC. Thus, active treatments for those patients might be required.

Screening of MicroRNA Related to Irradiation Response and the Regulation Mechanism of miRNA-96-5p in Rectal Cancer Cells.

Neoadjuvant chemoradiotherapy has been widely used in the treatment of locally advanced rectal cancer due to the excellent advantages of irradiation in cancer therapy. Unfortunately, not every patient can benefit from this treatment, therefore, it is of great significance to explore biomarkers that can predict irradiation sensitivity. In this study, we screened microRNAs (miRNAs) which were positively correlated with irradiation resistance and found that miRNA-552 and miRNA-183 families were positively correlated with the irradiation resistance of rectal cancer, and found that high expression of miRNA-96-5p enhanced the irradiation resistance of rectal cancer cells through direct regulation of the GPC3 gene and abnormal activation of the canonical Wnt signal transduction pathway. Based on the radioreactivity results of patient-derived xenograft models, this is the first screening report for radio-resistant biomarkers in rectal cancer. Our results suggest that miRNA-96-5p expression is an important factor affecting the radiation response of colorectal cancer cells.

Adding Adjuvants to Fluoropyrimidine-based Neoadjuvant Chemoradiotherapy for Locally Advanced Rectal Cancer: An Option Worthy of Serious Consideration.

The application of fluoropyrimidine-based neoadjuvant chemoradiotherapy (Fu-nCRT) of locally advanced rectal cancer (LARC) has become a common therapeutic regimen. In order to improve the efficacy and enable more patients to benefit from this treatment, an accumulation of studies have been carried out on the auxiliary use of other drugs with Fu-nCRT. However, due to specific challenges and the potential opportunities that coexist in this field, a more reasonable approach to the mode of treatment remains to be explored. In this review, we have summarized the results of the studies on the combination of Fu-nCRT with cytotoxic drugs, anti-tumor angiogenesis, and anti-EGFR agents, as well as the status of the application of immune checkpoint inhibitors in the neoadjuvant therapy of LARC patients.

Analysis of influencing factors of no/low response to preoperative concurrent chemoradiotherapy in locally advanced rectal cancer.

The aim of this study is to investigate the influencing factors associated with no/low response to preoperative concurrent chemoradiotherapy (CCRT) for locally advanced rectal cancer (LARC) patients. A total of 79 patients were included in this prospective study. Fifteen factors that might affect the resistance to CCRT were included in this logistic regression analysis, these factors include the general clinical data of patients, the expression status of tumor stem cell marker CD44v6 and the volumetric imaging parameters of primary tumor lesions. We found that the no/low response status to preoperative CCRT was positively correlated with the real tumor volume (RTV), the total surface area of tumor (TSA), and CD44v6 expression, whereas negatively correlated with the tumor compactness (TC). According to the results of logistic regression analysis, two formulas that could predict whether or not no/low response to preoperative CCRT were established. The Area Under Curve (AUC) of the two formulas and those significant measurement data (RTV, TC, TSA) were 0.900, 0.858, 0.771, 0.754, 0.859, the sensitivity were 95.8%, 79.17%, 62.50%, 95.83%, 62.5%, the specificity were 70.9%, 74.55%, 83.64%,47.27%, 96.36%, the positive predictive values were 58.96%, 57.58%, 62.51%,44.23%, 88.23%, the negative predictive values were 97.48%, 89.13%, 83.64%, 96.29%, and 85.48%, respectively.

Volumetric imaging parameters are significant for predicting the pathological complete response of preoperative concurrent chemoradiotherapy in local advanced rectal cancer.

Preoperative concurrent chemoradiotherapy (CCRT) as the standard treatment for locally advanced rectal cancer (LARC) has been widely used in clinic. Its efficiency influences the prognosis and the selection of subsequent treatment. The current criteria for evaluating the prognosis of patients with extremely sensitive preoperative CCRT include the clinical complete remission response (cCR) and pathological complete response (pCR), but those with cCR may not necessarily achieve pCR, and the pCR can be confirmed only after surgery. Some scholars believe that patients with pCR after CCRT can be categorized as 'watch and wait'. Therefore, it is extremely important to find a way to predict the pCR status of patients before therapy. In this study, we examined the expression of stem cell markers and obtained direct and derivative volumetric imaging parameters before treatment. Subsequently, these factors and the general clinical data were adopted into a regression model, and the correlation between them and the pCR was analyzed. We found that the pCR of LARC was positively correlated with tumor compactness (TC), whereas it was negatively correlated with approximate tumor volume (ATV), real tumor volume (RTV), total surface area of the tumor (TSA) and tumor maximum longitudinal length (TML). In these meaningful predictors, the positive predictive values and the negative predictive values of TC were 74.73% and 94.61%, respectively. Compared with other possible predictors, TC is the most encouraging predictor of pCR. Our findings provide a way for clinicians to predict the sensitivity of preoperative CCRT and will help to select individualized treatment options for LARC patients.

Gender differences in colorectal cancer survival: A meta-analysis.

A meta-analysis was conducted to determine the influence of gender on overall survival (OS) and cancer-specific survival (CSS) in colorectal cancer patients. Major databases were searched for clinical trials, which compare survival differences between male and female for colorectal cancer patients. A list of these studies and references, published in English and Chinese from 1960 to 2017, was obtained independently by two reviewers from databases such as PubMed, Medline, ScienceDirect, the China National Knowledge Infrastructure (CNKI) and Web of Science. Overall survival and cancer-specific survival were compared using Review Manager 5.3. Females had significantly better OS (hazard ratio [HR] = 0.87; 95% confidence interval [CI] = 0.85-0.89) and CSS (HR = 0.92; 95% CI = 0.89-0.95) than males after meta-analysis. These results suggest that gender seems to be a significant factor influencing survival results among colorectal cancer patients.

Overall survival of patients with KRAS wild-type tumor treated with FOLFOX/FORFIRI±cetuximab as the first-line treatment for metastatic colorectal cancer: A meta-analysis.

The addition of cetuximab to FOLFIRI or FOLFOX as the first-line treatment for metastatic colorectal cancer (mCRC) was shown to reduce the risk of disease progression and increase the chance of response in patients with KRAS wild-type disease. An updated systematic meta-analysis was undertaken to determine the efficacy of cetuximab plus FOLFIRI or FOLFOX.Major databases were searched to identify RCTs investigating wild-type KRAS mCRC after the first-line treatment, and treatment with FOLFOX/FORFIRI ±â€Šcetuximab was compared. Data on clinical efficacy and safety were pooled and compared by ORs, HRs, and 95% CIs.Five eligible trials with 1464 patients were included in the meta-analysis. Compared to FOLFOX/FORFIRI, cetuximab as the first-line therapy has improved overall survival (OS) (hazard ratio [HR] = 0.82, 95% confidence interval [CI]: 0.72-0.93, P = 0.003), progression-free survival (PFS) (HR = 0.66, 95% CI: 0.56 -0.77, P < 0.00001), and overall response rate (ORR) (odds ratio [OR] = 2.12, 95% CI: 1.70-2.65, P < 0.00001). However, Grade 3/4 AE was increased with the OR of 2.76 (95%CI: 2.01-3.78, P < 0.00001). The most common grade 3/4 toxicity in the wild-type KRAS population was neutropenia and diarrhea. For cetuximab plus FOLFIRI, there was a higher incidence of grade 3 or 4 diarrhea (OR = 1.76, 95% CI: 1.15-2.70, P = 0.01), but there was no significant difference for neutropenia (OR = 1.35, 95% CI: 1.00-1.83, P = 0.05).The addition of cetuximab in mCRC as the first-line treatment is a potential effective approach in the improved outcomes but associated with increased toxicity.

Robotic gastrectomy versus open gastrectomy in the treatment of gastric cancer.

BACKGROUND: Robotic gastrectomy (RG) has been developed to improve surgical quality and to overcome the limitations of conventional open gastrectomy (OG) for gastric cancer. The aim of this meta-analysis is to comprehensively compare the safety and efficacy between robotic surgery and open surgery for treating gastric cancer. METHODS: Major databases were searched for retrospective case-matched studies comparing RG and OG for treating gastric cancer. A list of these studies, published in English from 1990 to 2016, was obtained independently by two reviewers from databases such as PubMed, MEDLINE, ScienceDirect, the China National Knowledge Infrastructure and Web of Science. Intraoperative data, oncological outcomes and postoperative complications were compared using Review Manager 5.3. RESULTS: Seven studies involving 5970 patients with 606 cases of RG and 5364 cases of OG were included in this meta-analysis. Compared to OG, RG has a significantly longer operation time [weighted mean differences (WMD) = 63.72, 95 % confidence interval (CI) 33.83-93.61, P < 0.0001], lower blood loss (WMD: -129.74, 95 % CI -178.31 to -81.16, P < 0.00001) and shorter hospital stay (WMD = -2.39, 95 % CI -2.92 to -1.87; P < 0.00001). No statistical difference was noted based on the rate of overall postoperative complication, wound infection, bleeding, ileus and obstruction, abdominal collections and abscesses, and the rate of anastomotic leak in the RG versus OG. Postoperative oncological outcomes showed that there were also no statistical differences among the number of retrieved lymph nodes, proximal resection margin, distal resection margin except for tumor size (WMD = -1.60; 95 % CI -2.96 to -0.25; P = 0.02). CONCLUSION: The results of this meta-analysis suggest that RG will be more accessible than conventional OG for gastric cancer. However, more prospective, well-designed, multicenter, randomized controlled trials are necessary to further evaluate the safety and efficacy as well as the long-term outcome of this technology.

Clinical observation of the therapeutic effects of pegylated recombinant human granulocyte colony-stimulating factor in patients with concurrent chemoradiotherapy-induced grade IV neutropenia.

The aim of the present study was to investigate the efficacy and side-effects of preventive treatment with pegylated recombinant human granulocyte colony-stimulating factor (PEG-rhG-CSF) on concurrent chemoradiotherapy-induced grade IV neutropenia and to provide a rational basis for its clinical application. A total of 114 patients with concurrent chemoradiotherapy-induced grade IV neutropenia were enrolled. A randomized approach was used to divide the patients into an experimental group and a control group. The experimental group included three subgroups, namely a P-50 group, P-100 group and P + R group. The P-50 group had 42 cases, which were given a single 50-µg/kg subcutaneous injection of PEG-rhG-CSF. The P-100 group had 30 cases, which received a single 100-µg/kg subcutaneous injection of PEG-rhG-CSF. The P + R group comprised 22 cases, which were given a single 50-µg/kg subcutaneous injection of PEG-rhG-CSF and rhG-CSF 5 µg/kg/day; when the absolute neutrophil count (ANC) was ≥2.0×109/l, the administration of rhG-CSF was stopped. The control group (RC group) comprised 20 patients, who received rhG-CSF 5 µg/kg/day by subcutaneous injection until the ANC was ≥2.0×109/l. Changes in the neutrophil proliferation rate and ANC values over time, the neutropenic symptom remission time and incidence of adverse drug reactions were analyzed statistically in each group of patients. In the experimental group, the neutrophil proliferation rate and ANC values were significantly higher than those in the control group; the clinical effects began 12-24 h after treatment in the experimental group, and indicated that the treatment improved neutropenia in ~48 h after treatment. There was no significant difference in the neutrophil proliferation rate and ANC values between the P-50 and P+R groups. In the experimental group, the remission time of neutropenia-induced fever and muscle pain after administration was significantly shorter than that in the control group, with a statistically significant difference (P<0.05). The adverse drug reaction rates showed no significant difference between the experimental group and the control group. PEG-rhG-CSF had good efficacy and safety in the treatment of concurrent chemotherapy-induced grade IV neutropenia. For the treatment of concurrent chemotherapy-induced grade IV neutropenia, a single subcutaneous injection of 50 µg/kg PEG-rhG-CSF is the recommended dose. The effects begin at 12-24 h; if the ANC values are not significantly improved during this time, no supplementary administration of rhG-CSF is necessary.

[Effect of silencing HIF-1α by RNA interference on adhesion and invasion of the human nasopharyngeal carcinoma cell line CNE-1].

OBJECTIVE: To investigate the effects of HIF-1α on adhesion and invasion of human nasopharyngeal carcinoma CNE-1 cells under hypoxia and underlying molecular mechanisms. METHODS: CoCl2was used to mimic tumor hypoxic microenvironment. mRNA and protein expressions of HIF-1α, E-cadherin and CXCR4 in CNE-1 cells at different hypoxic time phases were detected by RT-PCR and ELISA respectively. The influences of silencing HIF-1α using RNA interference on E-cadherin and CXCR4 expressions were evaluated. Adhesion test Transwell invasion test were used to evaluate the effects of HIF-1α gene silencing on cell adhesion and invasion. RESULTS: Under hypoxia, HIF-1α mRNA expression in CNE-1 cells was stable, but its protein expression increased obviously (P<0.05). Both mRNA and protein expressions of E-cadherin were decreased significantly with prolonged hypoxia, while mRNA and protein expressions of CXCR4 increased significantly (P<0.05). After silencing HIF-1α gene, expression of E-cadherin protein was up-regulated, but with down-regulated expression of CXCR4 protein, with a decrease significantly in adhesion rate or invasive cell number of CNE-1 cells (P<0.05). CONCLUSIONS: Hypoxia can increase HIF-1α protein expression in nasopharyngeal carcinoma cell line CNE-1. Silencing HIF-1α by RNA interference can reduce inhesion and invasion abilities of CNE-1 cells, which may be mediated by down-regulating E-cadherin expression and up-regulating CXCR4 expression.

[Clinical observation of the salvage therapy using pegylated recombinant human granulocyte colony stimulating factor for grade IV neutropenia induced by concurrent chemoradiotherapy].

OBJECTIVE: To investigate the efficacy and safety of pegylated recombinant human granulocyte colony stimulating factor (PEG-rhG-CSF) in the salvage therapy for the grade IV neutropenia induced by concurrent chemoradiotherapy, and to provide evidence for its clinical rational application. METHODS: 114 malignant tumor patients suffered with grade IV neutropenia induced by concurrent chemoradiotherapy were treated in the following groups. In the P-50 group, 42 patients received a single subcutaneous injection of 50 µg/kg PEG-rhG-CSF. In the P-100 group, 30 patients received a single subcutaneous injection of 100 µg/kg PEG-rhG-CSF. In the P+R group, 22 patients received a single subcutaneous injection of 50 µg/kg PEG-rhG-CSF and multiple subcutaneous injections of 5 µg×kg(-1)×d(-1) rhG-CSF, until the absolute neutrophil count (ANC) ≥ 2.0×10(9)/L. In the R group, 20 patients received multiple subcutaneous injections of 5 µg×kg(-1)×d(-1) rhG-CSF, until ANC ≥ 2.0×10(9)/L. The P-50, P-100 and P+R groups were experimental groups, and the R group was defined as control group. In each group, the neutrophil proliferation rate and the neutrophil counts at different time points, the period of neutropenia symptom relief, and the rate of adverse reactions induced by above drugs were analyzed. RESULTS: Both neutrophil proliferation rates and neutrophil counts in the patients of experimental groups at different time points were significantly higher than those in the control group. In the experimental groups the period of the clinical effect began in 12-24 hours, and the conditions of neutropenia were improved in 36 hours. In the experimental groups, the period of the symptom relief such as fever and skeletal muscle pain was (30.00 ± 7.48) hours and (30.00 ± 5.10) hours, respectively, significantly shorter than (72.00 ± 17.89) hours and (59.00 ± 11.46) hours in the control group (P < 0.05). The adverse drug reaction rate was 26.1% in the experimental groups and 25.0% in the control group (P > 0.05). CONCLUSIONS: For the treatment of grade IV neutropenia induced by concurrent chemoradiotherapy, PEG-rhG-CSF is effective and safe. The recommend dose of this drug for the salvage therapy for those patients is a single hypodermal injection of 50 µg/kg. Usually it becomes effective in 12-24 hours.

[Expression of E-cadherin in nasopharyngeal carcinoma and its relationship with cervical lymph node metastasis].

OBJECTIVE: To investigate the expression of E-cadherin in nasopharyngeal carcinoma (NPC) and its relationship with cervical lymph node metastasis. METHODS: The expression of E-cadherin in 80 patients with NPC was detected by immunohistochemistry. RESULTS: Lower expression of E-cadherin was associated with advanced N-stage of the tumor (P = 0.018). There was no significant correlation between the expression of E-cadherin and lymph node size (P = 0.435). The expression of E-cadherin was higher in patients with cervical lymph node metastasis limited to a single area than that distributing in some scattered areas (P = 0.000). There was a trend that the expression of E-cadherin in the cases with the tumor and lymph nodes in the same side was higher (56.5%) than that in the patients with bilateral lymph node metastases (32.6%), however, the difference was not significant (P = 0.059). The expression rates of E-cadherin in patients with lymph node metastasis in levels II, III and Va were higher than that in levels I, IV, Vb and VI, but with a non-significant difference (P = 0.059). CONCLUSION: The expression of E-cadherin has influence on the lymph node metastasis in nasopharyngeal carcinoma. E-cadherin expression is negatively correlated with the numbers of the lymph node metastases and the metastasis distance, i.e. a lower expression of E-cadherin leads to an advanced N-stage. The lymph node metastasis of nasopharyngeal cancer from above to below is more considerably influenced by E-cadherin expression than the metastasis towards contralateral lymph nodes.

[Association of single nucleotide polymorphism of MnSOD gene with carcinogenesis and development of esophageal squamous cell carcinoma].

OBJECTIVE: To investigate the association of single nucleotide polymorphism (SNP) of manganese superoxide dismutase (MnSOD) gene with carcinogenesis and progression of esophageal squamous cell carcinoma. METHODS: The MnSOD9 T-->C SNP was genotyped by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis in 103 patients with esophageal squamous cell carcinoma and 195 healthy controls. RESULTS: A significant difference was observed in the MnSOD allelotype distribution among esophageal squamous cell carcinomas and healthy controls (chi(2) = 4.645, P < 0.05). Individuals with the 9 C allele had a significantly higher risk to develop esophageal squamous cell carcinoma compared with those with the TT allele. The frequency of C allelotype among patients with lesions of different lengths ( 5 cm) was 16.3% and 36.7%, respectively. A significant difference was observed in the MnSOD allelotype distribution between patients with lesions of different lengths (chi(2) = 5.147, P < 0.05). No significant association of the MnSOD polymorphism at 9 T-->C with the tumor site, maximal length and clinical staging was found in esophageal squamous cell carcinoma. CONCLUSION: Single nucleotide polymorphism (SNP) of MnSOD gene may be correlated with the susceptibility and disease progression of esophageal squamous cell carcinoma, and may become a tumor marker for prediction of this cancer.

Pathological analysis of clinical target volume margin for radiotherapy in patients with esophageal and gastroesophageal junction carcinoma.

PURPOSE: To clarify the radiotherapy clinical target volume (CTV) margin needed for esophageal squamous-cell carcinoma (SCC) and gastroesophageal junction (GEJ) adenocarcinoma. METHODS AND MATERIALS: Surgical specimens of esophageal SCC (n = 34) and GEJ adenocarcinoma (n = 32) were prospectively collected and analyzed for microscopic spread along the esophagus and GEJ both proximally and distally from gross tumor and for lymph node (LN) metastasis. RESULTS: For SCC, the mean microscopic spread beyond the gross tumor was 10.5 +/- 13.5 mm proximally (<30 mm in 32 of 34 cases) and 10.6 +/- 8.1 mm distally (<30 mm in 33 of 34 cases). For GEJ adenocarcinoma, the spread was 10.3 +/- 7.2 mm proximally (<30 mm in 29 of 29 cases) and 18.3 +/- 16.3 mm distally (<30 mm in 27 of 32 cases). The extent of microscopic spread of cancer was significantly associated with pathologic T stage (p = 0.012). LN metastases were observed in 12 (35%) of 34 patients with middle and lower esophageal SCC and 15 (47%) of 32 patients with GEJ adenocarcinoma. CONCLUSIONS: The extent of microscopic spread within esophagus (recommended CTV margin) was <30 mm in about 94% of cases of esophageal cancer, except for distal microscopic spread in GEJ adenocarcinoma, in which 50 mm was needed to cover about 94% of cases.