Wei-Peng Hu

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.

Esophageal luminal stenosis is an independent prognostic factor in esophageal squamous cell carcinoma

Background Predictive value of preoperative endoscopic characteristic of esophageal tumor has not been fully evaluated. The aim of this study is to investigate the impact of esophageal luminal stenosis on survival for patients with resectable esophageal squamous cell carcinoma (ESCC). Methods The clinicopathologic characteristics of 623 ESCC patients who underwent curative resection as the primary treatment between January 2005 and April 2009 were retrospectively reviewed. The esophageal luminal stenosis measured by endoscopy was defined as a uniform measurement preoperatively. The impact of esophageal luminal stenosis on patients’ overall survival (OS) and relation with other clinicopathological features were assessed. A Cox regression model was used to identify prognostic factors. Results The results showed that OS significantly decreased in patients with manifest stenotic tumor compared with patients without luminal obstruction (P<0.05). Considerable esophageal luminal stenosis was associated with a higher T stage, longer tumor length, and poorer differentiation (all P<0.05). In multivariate survival analysis, esophageal luminal stenosis remained as an independent prognostic factor for OS (P= 0.036). Conclusions Esophageal luminal stenosis could have a significant impact on the OS in patients with resected ESCC and may provide additional prognostic value to the current staging system before any cancer-specific treatment.

The role of mitochondrial folate enzyme MTHFD1L in esophageal squamous cell carcinoma

Abstract Objective: The lack of novel therapeutic targets poses the major challenge to prolong survival and improve the quality of life for esophageal squamous cell carcinoma (ESCC). Methylenetetrahydrofolate dehydrogenase 1-like (MTHFD1L) plays critical roles in folate cycle maintenance. However, little information is available concerning the role of MTHFD1L in cancer cells, and no studies have addressed such issues in esophageal cancer. Materials and method: Surgical cancer and adjacent normal esophageal tissues were obtained from patients with esophagectomy and esophagogastrostomy for ESCC. Western blot, immunohistochemistry and Quantitative RT-PCR were performed to evaluate protein and RNA expression levels of MTHFD1L. Knockdown of MTHFD1L expression was achieved by using short hairpin RNA. The effects of MTHFD1L silencing on ESCC cell proliferation and apoptosis were assessed by the MTT assay, Celigo assays, Annexin V FACS assay and Caspase-3/7 array in vitro. Results: Twenty-three paired cancer and adjacent normal esophageal tissues from patients with ESCC were included in this study. MTHFD1L protein and RNA expression levels were significantly upregulated in ESCC tissue as compared with normal tissue. High expression of MTHFD1 was also detected in two esophageal cancer cell lines (TE-1 and EC109). Knockdown of MTHFD1L expression inhibited the proliferation of TE-1 cells, and the apoptosis was distinctly increased following shMTHFD1L infection. Conclusions: Our preliminary study highlighted for the first time that MTHFD1L might be involved in the development of ESCC, which may provide a new potential tumor-specific therapeutic targeting for anti-folate agents.

Missed diagnosis of esophageal leiomyoma leading to esophagectomy: a case report and review of literatures

Leiomyomas are the most common benign esophageal neoplasm. About half of them were smaller than 5 cm and asymptomatic with a stable size for many years. Esophageal leiomyomas that excess than 5 cm in size may develop as a consequence of giant one at rapid growth rate. This case report specifically describes a mid-aged woman who experienced a missed diagnosis of an esophageal leiomyoma over three years, which was covered by mediastinal thymolipoma and it subsequently developed as a giant tumor occupying the entire esophagus that makes the simple enucleation impossible. A surgical intervention of esophagectomy had to be performed to manage this entity.

Prognostic power of lymph node station ratio for resected esophageal squamous cell carcinoma patients deserves additional investigation

Dear Editor, We read with great interest the report by Fu et al on the investigation of the prognostic value of the lymph node (LN) station ratio (SR, metastatic LN stations/examined LN stations) in esophageal squamous cell carcinoma (ESCC) patients. This study developed a new N category, which was demonstrated to provide more detailed prognostic information than the current N category. A standard staging system should be encompass the following major aspects: (1) the difference in survival time is small among patients classified into the same group by that criterion (homogeneity); (2) there are much greater differences in the survival times among patients classified into different groups (discriminatory ability); (3) mean survival time for a group classified as favorable is longer than the survival time for less favorable groups (monotonicity of gradients). In this study, log-rank test and c-index were used for measuring both the discriminatory power and monotonicity of the gradient, and the homogeneity was explored by performing the likelihood ratio (LR) test. Thus, this study has demonstrated statistically convincing evidence for that SR category has a superior prognostic ability relative to the AJCC pN category in ESCC patients. However, some points of the manuscript warrant discussion. First, since the radical two-field lymph node dissection with a qualified number of resected lymph nodes (>15) was done for each patient included, the value of LN stations was confinedwithin a certain narrow range (median 7, mean ± SD 7.67 ± 2.25). In this case, the prognostic power of examined LN stations was limited considerably, and the main determinant of SR was the metastatic LN stations. Second, the authors did not describe the process to select the arithmetic method to describe metastatic LN stations and examined LN stations. Readers might argue that other statistical models should be examined, such as arithmetic addition (metastatic stations + 1/ examined stations). Simple combination may produce adverse effects by impairing the homogeneity, discrimination, or monotonicity of each predictable marker. To further prove the point that the SR stage can properly represent both the quantitative accuracy and extent of LN metastasis, evaluation of the separate prognostic performance of examined LN stations and metastatic LN stations is mandatory to be added in the results section Another notable limitation is the lack of an external validation cohort to access the prognostic performance of this modified N category. A validation cohort is needed to further prove the improved prognostic ability of the new T-SR-M staging system into daily clinical practice. In short, the authors have proposed a revised N category which was demonstrated with a superior prognostic ability as compared with the AJCC pN category in ESCC patients after radical esophagectomy. Given the above-mentioned potential limitations, the prognostic power of this new N staging needs further investigation.

Prognostic significance and role in TNM stage of tumor deposits in esophageal cancer

Background Tumor deposits (TDs) are now observed in esophageal cancer (EC), but the role of TDs is seldom elucidated. This study aimed to research the prognostic significance and the role of TDs in EC. The patients with primary EC, who had undergone curative esophagectomy in West China Hospital from May 2005 to May 2011 were retrospectively enrolled. Methods The prognosis and clinicopathological traits were compared between tumor deposits positive (TDP) and tumor deposits negative (TDN) groups in all patients and TNM 0-IV stages respectively. Results In our study, 1,044 patients were enrolled, with 948 (90.8%) in TDN group and 96 (9.2%) in TDP group. TDP group had significantly more advanced EC and worse prognosis (all P<0.001) than TDN group in all patients, TNM II stage and TNM III stage. The prognosis of TDP group in TNM II stage was significantly worse than TDN patients in TNM III stage (P<0.001), and the worst prognosis was always found in patients with at least one TD regardless of the number of metastatic lymph node is. Conclusions Patients in TDP subgroup had more advanced EC and worse prognosis than those in TDN subgroup. It might be more reasonable to be regarded as an indicator of stage migration in EC.