Yun-Cang Wang

Neuroendocrine carcinoma of the esophagus: clinical characteristics and prognostic evaluation of 49 cases with surgical resection

BACKGROUND The clinicopathological features and optimum treatment of esophageal neuroendocrine carcinoma (NEC) are hardly known due to its rarity. Therefore, we conducted a retrospective study to analyze the clinical characteristics and prognosis of patients with surgically resected esophageal NEC. METHODS We collected clinicopathological data on consecutive limited disease stage esophageal NEC patients who underwent esophagectomy with regional lymphadenectomy in West China Hospital from January 2007 to December 2013. RESULTS A total of forty-nine patients were analyzed retrospectively. The mean age of the patients was 58.4±8.2 years with male predominance. Fifty-five percent of the esophageal NEC were located in the middle thoracic esophagus. Histologically, 28 (57.1%) patients were found to be small cell NECs. Fifty-one percent of the patients were found to have lymph node metastasis. According to the 2009 American Joint Committee on Cancer (AJCC) staging system for esophageal squamous cell carcinoma, 9 patients were at stage I, 21 patients stage II, and 19 patients stage III. Twenty-six patients (53.1%) received adjuvant therapy. After a median follow-up of 44.8 months [95% confidence interval (CI), 35.2-50.4 months], the median survival time of the patients was 22.4 months (95% CI, 14.0-30.8 months). The 1-year and 3-year survival rates for the whole cohort patients were 74.9% and 35.3%, respectively. In univariate analysis, TNM staging, lymph node metastasis and adjutant therapy significantly influenced survival time. In multivariate analysis, TNM staging was the only independent prognostic factor. CONCLUSIONS Esophageal NEC has a poor prognosis. The 2009 AJCC TNM staging system for esophageal squamous cell carcinoma may also fit for esophageal NEC. Surgery combined with adjuvant therapy may be a good option for treating limited disease stage esophageal NEC. Further prospective studies defining the optimum therapeutic regimen for esophageal NEC are needed.

Radiotherapy, lobectomy or sublobar resection? A meta-analysis of the choices for treating stage I non-small-cell lung cancer.

Whether stereotactic ablative radiotherapy (SABR) is comparable to surgery in treating stage I non-small-cell lung cancer (NSCLC) is unknown. Therefore, we conducted this meta-analysis to compare the efficacy of SABR with that of surgery in treating stage I NSCLC. A systematic literature search in PubMed, Embase, Cochrane Library databases and Google Scholar as well as the American Society of Clinical Oncology was conducted to identify relevant studies dated through 31 December 2015. Data including 3-year survival rate, overall survival (OS) and 3-year loco-regional control (LRC) rates were extracted and analysed. No complete randomized controlled trials but 12 cohort studies were included with a total of 13 598 patients. Meta-analysis showed a significantly lower 3-year survival rate (risk ratio = 0.78; 95% confidence interval [CI] = [0.68, 0.90]; P = 0.001) and shorter OS (hazard ratio =1.60; 95% CI = [1.24, 2.06]; P < 0.001) for patients treated with SABR compared with surgery. No difference in the 3-year LRC rate was observed between SABR and surgery (risk ratio = 0.95; 95% CI = [0.82, 1.09]; P = 0.453). Subgroup analysis was conducted on the basis of surgical procedures. In the subgroup analysis, SABR was found to yield significantly shorter OS than lobectomy (hazard ratio = 1.68; 95% CI = [1.09, 2.60]; P = 0.018), whereas SABR was comparable to sublobar resection in terms of 3-year survival rate, OS and 3-year LRC rate. Our meta-analysis found that lobectomy yielded better survival outcomes than SABR, whereas SABR yielded comparable rates when compared with sublobar resection. Lobectomy is still the preferred method for treating earlystage NSCLC. Well-designed and multicentred randomized controlled trials with large sample sizes, however, are needed to confirm and update our conclusions.

Neoadjuvant chemoradiotherapy or chemotherapy? A comprehensive systematic review and meta-analysis of the options for neoadjuvant therapy for treating oesophageal cancer

Neoadjuvant therapy followed by surgery is a standard treatment for locally advanced oesophageal cancer. However, the roles of neoadjuvant chemoradiotherapy and chemotherapy in treating oesophageal cancer remain controversial. In this comprehensive meta-analysis, we examine the efficacy of adding radiotherapy to neoadjuvant chemotherapy for treating oesophageal cancer as reported in qualified randomized controlled trials (RCTs). We conducted a systematic literature search using PubMed, Embase, Cochrane Library databases, Google Scholar and the American Society of Clinical Oncology database to identify relevant studies up to 31 March 2016. Data including the pathological complete response rate, R0 resection rate and 3-year survival rate were extracted and analysed. Five qualified RCTs were included with a total of 709 patients. Meta-analysis showed that neoadjuvant chemoradiotherapy significantly increases the rates of pathological complete response and R0 resection in patients with oesophageal adenocarcinoma or squamous cell carcinoma (SCC). However, we found a significantly increased 3-year survival rate only in oesophageal SCC patients treated with neoadjuvant chemoradiotherapy compared with neoadjuvant chemotherapy (56.8 and 42.8%, respectively); relative risk (RR): 1.31 [95% confidence interval (CI) 1.10-1.58, P = 0.003]. In oesophageal adenocarcinoma patients, no significant survival benefit of neoadjuvant chemoradiotherapy was found compared with neoadjuvant chemotherapy alone (46.3 and 41.0%, respectively; RR: 1.13, 95% CI 0.88-1.45, P = 0.34). Our meta-analysis adds to the evidence showing that neoadjuvant chemoradiotherapy should be the standard preoperative treatment strategy for locally advanced oesophageal SCC. For oesophageal adenocarcinoma, neoadjuvant chemotherapy alone may be the best preoperative treatment strategy to avoid the risk of adverse effects of radiotherapy.

Long noncoding RNAs are novel potential prognostic biomarkers for esophageal squamous cell carcinoma: an overview.

Esophageal squamous cell carcinoma (ESCC) still has a poor prognosis. The prognostic biomarkers of ESCC are not yet well established. Long noncoding RNAs (lncRNAs) have recently been intensively investigated in various cancers including ESCC, and are found to be closely correlated to ESCC. Dysregulated expression of lncRNAs was widely observed in ESCC tumor tissue and was closely related to the tumorigenesis and progression of ESCC. More and more studies have found that lncRNAs were significantly correlated with the prognosis and diagnosis of patients with ESCC. Therefore, all those accumulating evidence indicated that lncRNAs could serve as a prognostic biomarker of ESCC. In this, we summarized the relation between lncRNAs and ESCC as well as the potential biomarker role of lncRNAs in ESCC, especially the prognostic value of lncRNAs. Our current review highlighted the need of further studies to explore the biomarker functions as well as therapeutic values of lncRNAs in ESCC.

Left thoracotomy for middle or lower thoracic esophageal carcinoma: still Sweet enough?

BACKGROUND Esophagectomy via left thoracotomy (the Sweet procedure) has long been the conventional route for resection of esophageal carcinoma, especially in China. However, this procedure is being increasingly critiqued, mainly regarding the lymphadenectomy. The objective of this study was to compare the Sweet procedure with the right upper mediastinal lymph node resection (MS) and Ivor-Lewis (IL) procedure in the treatment of middle or lower thoracic esophageal squamous cell carcinoma (OSCC-MLT) in terms of lymphadenectomy, postoperative complications, and long-term survival. METHODS A total of 336 OSCC-MLT patients underwent radical intent surgery (188 with MS and 148 with IL procedure) between January 2007 and September 2013 in our hospital. After propensity score matching, 129 patients from each procedure were included. The efficacy of lymph node dissection at each station was estimated by the index of estimated benefit from lymph node dissection (IEBLD). RESULTS IEBLD is relatively high in stations 2L, 2R, 8, 16 and 17. The metastasis rates and ratios were similar between the MS and IL procedures at each station. The MS procedure significantly outperformed the IL procedure with a shorter operating time (212 vs. 317 min), shorter in-hospital stay (10.7 vs. 15.3 days), and fewer postoperative complications (30.2% vs. 43.4%). However, the 5-year survival rates were not significantly different between the two procedures (46.9% vs. 44.0%). CONCLUSIONS The MS procedure of esophagectomy is not inferior to the IL procedure in efficiency, moreover the MS procedure is safer.

Notch Signaling Pathway Is Inhibited in the Development of Barrett’s Esophagus: An In Vivo and In Vitro Study

Objective To explore the role of Notch signaling in the development of Barretts esophagus. Methods Patients with esophagectomy and gastric interposition were recruited as a human model of gastroesophageal reflux disease. The expressions of Notch signaling genes in normal esophagus from surgical specimen and columnar metaplasia in the esophageal remnant after esophagectomy were evaluated by real time quantitative Polymerase Chain Reaction (RT-qPCR) and immunohistochemistry (IHC). For in vitro experiments, Het-1A cells were treated with hydrochloric acid, deoxycholic acid, mixture of hydrochloric acid and deoxycholic acid, or Notch1-siRNA, and expressions of Notch1, Hes1, MUC2, and K13 were evaluated via RT-qPCR and western blot. Results Samples were obtained from 36 patients with columnar metaplasia in the esophageal remnant. Both IHC and RT-qPCR indicated that Notch1 and Hes1 expressions were significantly higher in normal esophagus than that in metaplasia. Hydrochloric acid and deoxycholic acid suppressed Notch1, Hes1, and K13 expressions, in concert with increasing MUC2 expressions. Notch inhibition by Notch1-siRNA contributed to the downregulation of Notch1, Hes1, and K13 expressions, whereas MUC2 expression was enhanced. Conclusions Both hydrochloric acid and deoxycholic acid could suppress Notch signaling pathway in esophageal epithelial cells, and inhibited Notch signaling has important functions in the development of Barretts esophagus.

High expression of Ki-67 is an independent favorable prognostic factor for esophageal small cell carcinoma

Background The prognostic value of Ki-67 expression in small cell carcinoma of the esophagus (SCCE) has not been explored in any previous studies. Therefore, we conducted this retrospective study to investigate the prognostic role of Ki-67 in SCCE for the first time. Results A total of 44 patients were included for analysis. The baseline clinicopathological data of these SCCE patients shared similar characteristics with previous studies. Ten patients were at stage I, 17 at stage II, and the remaining 17 were at stage III. Postoperatively, 23 patients received adjuvant therapy. Twenty-eight patients were found to have a high expression of Ki-67 (> 50%). After a median follow-up time of 54.8 months, the median survival time of those patients was 22.1 months. Early TNM stage, application of adjuvant therapy, and high expression of Ki-67 (Hazard Ratio = 0.314, 95% CI: 0.127–0.774; P = 0.012) were found to be favorable prognostic factors of patients with SCCE. In subgroup analysis, adjuvant therapy could only bring significant survival benefit for patients with high expression of Ki-67 (P = 0.008). Materials and Methods Patients undergoing esophagectomy with lymphadenectomy for SCCE from January 2009 to January 2015 in our department were retrospectively analyzed. Data for analysis included demographic data, pathologic findings, tumor stage, adjuvant therapy, and survival time as well as Ki-67 index. Conclusions This study suggested that high expression of Ki-67 may not only serve as a favorable prognostic factor of SCCE but also an indication of providing adjuvant therapy for SCCE patients with surgical resection.BACKGROUND The prognostic value of Ki-67 expression in small cell carcinoma of the esophagus (SCCE) has not been explored in any previous studies. Therefore, we conducted this retrospective study to investigate the prognostic role of Ki-67 in SCCE for the first time. RESULTS A total of 44 patients were included for analysis. The baseline clinicopathological data of these SCCE patients shared similar characteristics with previous studies. Ten patients were at stage I, 17 at stage II, and the remaining 17 were at stage III. Postoperatively, 23 patients received adjuvant therapy. Twenty-eight patients were found to have a high expression of Ki-67 (> 50%). After a median follow-up time of 54.8 months, the median survival time of those patients was 22.1 months. Early TNM stage, application of adjuvant therapy, and high expression of Ki-67 (Hazard Ratio = 0.314, 95% CI: 0.127-0.774; P = 0.012) were found to be favorable prognostic factors of patients with SCCE. In subgroup analysis, adjuvant therapy could only bring significant survival benefit for patients with high expression of Ki-67 (P = 0.008). MATERIALS AND METHODS Patients undergoing esophagectomy with lymphadenectomy for SCCE from January 2009 to January 2015 in our department were retrospectively analyzed. Data for analysis included demographic data, pathologic findings, tumor stage, adjuvant therapy, and survival time as well as Ki-67 index. CONCLUSIONS This study suggested that high expression of Ki-67 may not only serve as a favorable prognostic factor of SCCE but also an indication of providing adjuvant therapy for SCCE patients with surgical resection.

Longitudinal study of esophageal mucosal damage after esophagectomy and gastric interposition: relationship between reflux-related mucosal injury and Notch signaling

Background Esophagectomy with gastric interposition could serve as a good human reflux model to study the molecular pathogenesis of esophageal mucosal damage induced by gastroesophageal reflux. This study was to investigate the role of Notch signaling in reflux injury of esophageal mucosa. Methods Patients undergoing Ivor-Lewis esophagectomy for early stage esophageal squamous cell carcinoma were included. Follow-ups were scheduled at 6, 18, 36 and 48 months postoperatively, including reflux symptom assessment, endoscopic and histological evaluation of esophageal mucosal damage. The expressions of Notch1 and its downstream target gene Hes1 were evaluated by real-time polymerase chain reaction (PCR) and immunohistochemistry (IHC). Results Forty-four out of 48 patients completed four follow-ups. Injuries of esophageal remnant confirmed by endoscopical and histological examinations were both more often with a longer postoperative period (P<0.05). The mRNA expression levels of Notch1 and Hes1 were decreased in a time-dependent manner after operation (P<0.001). Notch1 and Hes1 mRNA levels were significantly higher in normal squamous mucosa than in esophagitis, and higher in esophagitis than in metaplasia (P<0.05). Immunohistochemical study also demonstrated a similar protein expression pattern. Samples with endoscopic evidence of mucosal damage exhibited lower expression of Notch1 mRNA levels as compared to biopsies without visualized damage (P=0.035). Conclusions This is the first longitudinal study on Notch signaling in human esophagectomy model, our preliminary findings suggest decreased Notch signaling might be involved in the development of mucosa damage caused by gastroesophageal reflux.

Oesophageal adenocarcinoma has a higher risk of lymph node metastasis than squamous cell carcinoma: a propensity score-matched study

OBJECTIVES The pattern of lymph node metastasis is a predominant element in tumour biology, which is closely related to optimal therapeutic modality. Controversy remains as to which histopathology type of oesophageal cancer-adenocarcinoma or squamous cell carcinoma (SCC)-is more likely to have lymph node metastasis. Therefore, this study aimed to apply propensity score-matched analysis to draw an objective conclusion for providing initial evidence of the potential need for different therapeutic strategies for these 2 cancer types. METHODS A retrospective analysis of patients who underwent radical oesophagectomy with lymphadenectomy, but without preoperative treatment for pathologically and immunohistochemically diagnosed oesophageal adenocarcinoma or SCC, was conducted. Data for analysis included age, gender, body mass index, pathologic findings, procedures of oesophagectomy and rate of lymph node metastasis. Propensity score-matched analysis was conducted to eliminate the bias effects of confounding factors. RESULTS A total of 1204 patients (including 118 with adenocarcinoma and 1086 with SCC) from January 2012 to June 2016 was included for analysis. In the analysis of unmatched patients, those with adenocarcinomas had significantly larger mean numbers of positive lymph nodes (3.8 and 1.5, respectively; P < 0.001) and higher rates of lymph node metastasis (71.2% and 49.0%, respectively; P < 0.001) than those with an SCC. However, other confounding factors such as surgical procedures, tumour location, pT stage and lymphovascular invasion also differed significantly between the adenocarcinoma and SCC cases. In the analysis of 96 matched patients, those confounding factors were well matched, and cases of adenocarcinoma still had a significantly larger mean number of positive lymph node (4.5 and 1.8, respectively; P = 0.003) and higher rate of lymph node metastasis (75.0% and 45.8%, respectively; P = 0.003) than did those with SCC. CONCLUSIONS Cases of oesophageal adenocarcinoma had a higher risk of lymph node metastasis than did those with SCC in this series, which indicates that different therapeutic modalities should be applied for these 2 different malignant entities.

Prognostic value of right upper mediastinal lymphadenectomy in Sweet procedure for esophageal cancer

BACKGROUND The prognostic value of the right upper mediastinal lymph node dissection (RUMLND) for patients with middle or lower thoracic esophageal squamous cell carcinoma (ESCC-MLT) is still not well established yet. Our objective is to evaluate the prognostic role of the Sweet procedure plus right upper mediastinal lymph node dissection (MS) by comparing with the Sweet procedure with standard lymph node dissection (SS) in terms of long-term survival. METHODS Totally 1,477 ESCC-MLT patients underwent radical intent surgery (186 with MS, 1,291 with SS) at our department between January 2007 and September 2013. After propensity score matching (PSM), 186 patients from each group were matched and analyzed. The 5-year survival rates in two groups were compared by detailed stratifications in terms of clinical characteristics. RESULTS As for the prognostic role of RUMLND, patients treated with MS tended to obtain higher 5-year survival rate than patients treated with SS in univariate analysis (48.1% vs. 37.4%). Moreover, in multivariate analysis, MS yielded significant higher 5-year survival rate compared with SS (P=0.041). In addition, subgroup analyses of the survival between the MS and SS patients by detailed stratifications demonstrated the survival superiority in the MS group with age <60 years old, TNM stage III, number of lymph node dissection (LND) ≥15, as well as no using of postoperative adjuvant treatment. CONCLUSIONS The RUMLND in Sweet procedure is an independent prognostic factor for ESCC-MLT patients, especially for those with thoracic middle segment-located tumor, stage III or younger.