Luyan Shen

Survival after neoadjuvant chemotherapy versus neoadjuvant chemoradiotherapy for resectable esophageal carcinoma: A meta-analysis

The efficacy of surgery alone for patients with locally advanced esophageal cancer (EC) is still unsatisfactory. Presently, induction therapy followed by surgery is the standard treatment. Preoperative chemotherapy (CT) and chemoradiation (CRT) are proven effective induction therapies; however, few sample studies have addressed these treatments, thus, their superiority remains uncertain. We performed a systemic review and meta analysis to test the hypothesis that induction CRT prior to surgery could improve survival compared with induction CT alone.

Deregulated HOXB7 Expression Predicts Poor Prognosis of Patients with Esophageal Squamous Cell Carcinoma and Regulates Cancer Cell Proliferation In Vitro and In Vivo

Background We observed abnormal HOXB7 expression in esophageal squamous cell carcinoma (ESCC) previously. This study was to evaluate the prognostic significance of HOXB7 and reveal the potential mechanism. Methods Immunohistochemistry was used to confirm the abnormal expression of HOXB7 in ESCC. The prognostic significance of HOXB7 expression was analyzed in two independent cohorts. RNAi was used to establish two stable HOXB7-knockdown cell strains. CCK8 assay, cell growth curve assay, colony formation assay, flow cycle analysis and tumorigenicity assay in nude mice were employed to investigate the effect of HOXB7 on proliferation in vitro and in vivo. Results Immunohistochemistry confirmed the abnormal expression of HOXB7 in ESCC compared with paracancerous mucosa (18/23 vs. 9/23, p=0.039). HOXB7 expression was positively correlated with the T stage, lymph node metastasis and TNM stage. The median survival of patients with high HOXB7 expression was significantly shorter than that with low expression (45 months vs. 137 months, p = 0.007 for cohort 1; 19 months vs. 34 months, p = 0.001 for cohort 2). Multivariate survival analysis showed that HOXB7 expression was another independent prognostic factor (HR [95% CI] = 0.573 [0.341–0.963], p = 0.036 for cohort 1; HR [95%CI] = 0.543 [0.350–0.844], p = 0.024 for cohort 2). Experiments in vitro and in vivo showed that after knockdown of HOXB7, the proliferation rate dropped, growth rate descended, colony-formation ability reduced, G1-phase arrest occurred and the tumorigenicity reduced remarkably. Conclusions HOXB7 could promote cancer cell proliferation and might be an independent prognostic factor for patients with ESCC.

Advantages of positron emission tomography-computed tomography imaging in esophageal squamous cell carcinoma.

To explore the value of positron emission tomography-computed tomography (PET-CT) scan in esophageal squamous cell carcinoma (ESCC), we retrospectively summarize the results of PET-CT scan from 118 patients, with ESCC who underwent PET-CT scan in the different courses during treatment. Then, the results of PET-CT scan plus other conventional methods were analyzed to identify the value of PET-CT scan in diagnosis, staging, response evaluation, monitoring recurrence, and metastasis following treatment. It is suggested that PET-CT scan possess high value in diagnosis and gives more favorable indication in N and M staging. PET-CT scan should be translated into routine surveillance for postoperation follow up and is one of more helpful evaluators of response to chemoradiotherapy or chemotherapy.

Possible prediction of the response of esophageal squamous cell carcinoma to neoadjuvant chemotherapy based on gene expression profiling

Background Heterogeneous efficacy of neoadjuvant chemotherapy has led to controversies that have limited its application in clinical practice. Thus, we aimed to identify potential biomarkers predicting esophageal squamous cell carcinoma (ESCC) chemo-responsiveness by gene expression profiling. Methods CCK8 assay was used to evaluate the growth inhibitory effect of different concentrations of cisplatin and paclitaxel on the ESCC cell lines EC109, KYSE450, KYSE410, KYSE510, and KYSE150 to differentiate between chemosensitive and chemoresistant cell lines. Gene expression profiling and Real-time PCR were applied to analyze and validate the gene expression differences between chemosensitive and chemoresistant cell lines. IHC was conducted to examine the expression of selected target markers MUC4, MUC13, and MUC20 in 186 ESCC resection samples and the relationships between their expression and tumor regression grade was analyzed. Moreover, RNAi was conducted to instantly block the expression of MUC4, MUC13, and MUC20 to observe their influences on chemo-responsiveness. Results EC109 was found to be relatively sensitive to both cisplatin and paclitaxel, while KYSE410 was relatively resistant to cisplatin, KYSE510 was relatively resistant to paclitaxel. Gene expression profiling analysis showed that 2018 genes were differentially expressed in sensitive cell line compared to resistant cell lines. The expression patterns of MUC4, MUC13, MUC20 were validated. Low expression of MUC4 and MUC20 in resection samples was significantly correlated with better TRG. Blockage of MUC20 and MUC13 decreased the drug-resistance capacity and chemosensitivity, respectively. Conclusions MUC4 and MUC20 were identified as potential biomarkers for predicting the efficacy of neoadjuvant chemotherapy in ESCC patients.

The expression and prognostic significance of Mucin 13 and Mucin 20 in esophageal squamous cell carcinoma

BACKGROUND Mucin 13 (MUC13) and Mucin 20 (MUC20) are high molecular weight transmembrane O-linked glycoprotein secreted by epithelium and are widely overexpressed in epithelial tumor cells. Previously, it has been reported that MUC13 and MUC20 were prognostic molecular biomarkers of some epithelial tumors, but few has studied the relations between MUC13 or MUC20 expression and the prognosis of patients with esophageal squamous cell carcinoma (ESCC). Thus, the aim of our study was to explore this issue. MATERIALS AND METHODS Immunohistochemistry was used to detect the expressions of MUC13 and MUC20 in 186 patients with ESCC who received neoadjuvant chemotherapy followed by surgery. We analyzed the correlations between MUC13 or MUC20 expression and long-term survival of these patients. RESULTS The expression of MUC13 and MUC20 in ESCC mainly occurred in the cytoplasm. Among the 186 subjects, 53.8% had high MUC13 expression and 38.2% had high MUC20 expression. Univariate analysis showed that neither MUC13 nor MUC20 was significantly associated with long-term survival. When combining expression of MUC13 with MUC20, we found that the median survival time of patients with low MUC13/high MUC20 expression was significantly shorter than that of patients with high MUC13/low MUC20 expression (27.7  months vs. 59.5 months, P = 0.021). Multivariate analysis showed that combination of MUC13/MUC20 expression was an independent prognostic factor (hazard ratios = 0.531, 95% confidence interval: 0.299-0.944, P = 0.031). CONCLUSION A combination of MUC13/MUC20 expression was a potential prognostic marker for patients with ESCC, who received neoadjuvant chemotherapy followed by surgery.

Role of E2F-1 and its involving pathway in esophageal squamous cell carcinoma

Esophageal cancer is a lethal disease and the optimal therapy remains unclear. Neoadjuvant chemotherapy provides an increased chance of survival; therefore, we attempted to identify potential molecular markers that might improve evaluations of individual responses to therapy.

Chest Wall Resection and Reconstruction for Thoracic Tumor Invading the Chest Wall: A Report of 12 Cases

BACKGROUND AND OBJECTIVE Tumor involving the chest wall is a common clinical event, and if there are no distant metastases, complete resection of tumor and involved chest wall can give excellent results. The aim of this study is to report experience with chest wall resection and reconstruction (CWRR) for 12 patients who suffered thoracic malignant tumor involving chest wall, including the artificial materials used for reconstruction, soft tissue coverage, and our multidisciplinary CWRR approach. METHODS All characteristics of 12 cases of CWRR from Oct 2005 to Apr 2011 were reviewed, including preoperative treatment, surgical approach, resection range, reconstruction methods, the local and systematic complications and postoperative survival. RESULTS All 12 of these patients underwent radical resection and bony chest wall resection, with resultant bony chest wall defects ranging from 25 cm² to 700 cm², soft tissue defects of 56 cm² to 400 cm². The bony chest wall was reconstructed using polypropylene mesh, and repair of the soft tissue was carried out using the shifting muscle flaps, myocutaneous flaps and omental flaps. There was only one significant complication in these 12 cases where 1 case suffered respiratory failure and needed mechanical ventilation but recovered one month later. All 12 patients have survived to the end point of follow up. CONCLUSIONS Only thoracic surgery and reconstructive surgery work together can complete the complex CWRR which according the tumor discipline. Thoracic surgeons as the leader and reconstructive surgeons as the subsidiary and be familiar with reconstruction materials of bony chest wall and appropriate choice of soft tissue coverage is the key to achieve radical surgery and to ensure long-term survival.

Application of 18F-FDG PET/CT in Pulmonary Disease: A Report of 419 Cases

BACKGROUND AND OBJECTIVE The application and the value of PET/CT in lung cancer are on the way to development. The aim of this study is to summarize the data from 419 patients with pulmonary tumor or tumor-like disease and to explore the appliance of PET/CT. METHODS From Dec 2007 to Aug 2011, 594 patients with pulmonary tumor or tumor-like disease underwent PET/CT examination during the different course of treatment, which were treated by single surgery team from Peking University Cancer Hospital. Of these patients, 419 cases diagnosed pathologically were included into study. The clinicapathological and follow-up data were collected to analyze the value of PET/CT in diagnosis, TNM staging, therapy response evaluation and posttherapy monitoring. RESULTS Four hundred and nineteen cases comprised of 63 benign and 356 malignant, of which, 338 were primary lung cancer, and 18 were metastases. The SUVmax cutoff was defined as 2.5 to differentiate the benign and malignant disease. PET/CT obtained the role of diagnosis with sensitivity as 85.0%, specificity as 52.4%, accuracy rate as 79.2%, positive predictive value as 89.2% and negative predictive value as 42.9%, respectively. Of 338 primary cases, 275 underwent PET/CT at initial diagnosis, in which, 46 (16.7%) distant metastasis were found, including 8 additional metastasis not found by conventional utilities. Six of 43 recurrences were found by PET/CT following conventional examination. In T staging, SUVmax is positively correlated with diameter of tumors (P<0.05). In N staging, 610 stations of lymph nodes were resected from 168 cases, with 37 stations predicted as positive by PET/CT and 102 stations pathologically proven positive, therefore, calculating the sensitivity as 36.3%, specificity as 93.9%, accuracy rate as 84.3%, positive predictive value as 54.4% and negative predictive value as 88.0%, respectively. Ten patients underwent PET/CT scan for chemotherapy response evaluation, with SUVmax changing following T downstaging. CONCLUSION PET/CT is one optional method for diagnosis of pulmonary tumors. In TNM staging, PET/CT showed the superiority than conventional utilities in M staging, but possesses the high specificity but inferior sensitivity in N staging. Therefore, PET/CT should be used as routine examination for postoperation follow-up. Furthermore, PET/CT performed the outstanding role in chemotherapy response evaluation.

Overexpression of NRF2 is correlated with prognoses of patients with malignancies: A meta‐analysis

Previous published research has demonstrated that NRF2 expression is a poor prognostic factor for many malignancies. However, because of the small sample enrolled in a single study, it is difficult to draw valuable conclusions. Therefore, we hypothesized that NRF2 overexpression in cancer tissues may be associated with the prognoses of patients with solid malignancies, and conducted a systemic review and meta‐analysis.

Survival Analysis of 121 Stage N2-IIIa Non-small Cell Lung Cancer Patients Treated with Surgery

BACKGROUND AND OBJECTIVE It has still been controversial to treat N2-IIIa non-small cell lung cancer (NSCLC) patients by surgery or non-surgery. We retrospectively analysed the survival of 121 stage N2-IIIa NSCLC patients treated with surgery and explored their postoperatively long-term prognostic factors. METHODS All of 1,290 patients in Beijing Cancer Hospital underwent resection by single-surgeon-team, among which 121 cases with stage N2-IIIa were enrolled in the study. We retrospectively analysed the impact of gender, age, smoking, perioperative chemotherapy, incision, histological type, vascular tumor emboli, pTstage and tumor size on survival of stage N2-IIIa patients, and compared the survival between patients with single-and multi-station N2 metastasis, and between intraoperatively or postoperatively pathological N2 (IIIa1/a2) and preoperative N2 (IIIa3/a4). Univariate analysis was conducted by Kaplan-Meier curve, and significance test was performed by Log-rank test and Cox regression factor analysis was applicated for multivariate analysis. RESULTS The 5-yr of all the 121 cases was 43.6%, with a median survival time being 50.3 mo. Univariate analysis showed the 5-year survival rate in patients with single- and multi- station N2 metastasis were 58.3% and 25.5%, respectively (P=0.001), 5-year survival rate in patients with stage IIIa1/a2 and stag IIIa3/a4 were 52.7% and 38.4%, respectively (P=0.020). Multivariate analysis demonstrated that only single station N2 (HR=0.326, 95%CI: 0.186-0.572, P<0.001) and IIIa1/a2 (HR=0.494, 95%CI: 0.259-0.941, P=0.032) were independent prognostic factors for stage N2-IIIa lung cancer patients. CONCLUSIONS The prognosis of stage N2-IIIa NSCLC patients with single-station N2 metastasis were better than those with multi-station N2 metastasis. Besides, IIIa1/a2 patients had a better survival compared with stage IIIa3/a4 patients. A multi-disciplinary comprehensive treatment based on surgery may allow patients with high selective stage N2-IIIa NSCLC to obtain a comparatively satisfying long-term survival.
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