REG I Expression Predicts Long-term Survival among Locally Advanced Thoracic Squamous Cell Esophageal Cancer Patients Treated with Neoadjuvant Chemoradiotherapy Followed by Esophagectomy

Background The prognosis for patients with locally advanced thoracic esophageal cancer is extremely unfavorable. We have been administering neoadjuvant chemoradiotherapy (CRT) followed by esophagectomy to these patients and studying whether REG I expression in untreated endoscopic biopsy specimens is predictive of patient responsiveness to CRT and/or survival after treatment.Methods Between 1992 and 2003, 47 patients with T4 (direct invasion of adjacent organs) thoracic esophageal cancers were administered neoadjuvant CRT followed by esophagectomy. REG I expression was assessed in untreated endoscopic biopsy specimens and correlated with clinical and histological responses and survival in 37 patients who had also undergone curative surgery.Results Among the 37 cases that received CRT followed by surgery, the therapeutic response rate for neoadjuvant CRT was 68%, and a complete histological response in resected specimens from the primary lesion was achieved in 8 (22%) patients. These clinical and histological responses to neoadjuvant CRT did not significantly correlate with survival, however. By contrast, 9 patients were judged REG-positive based on analysis of their untreated endoscopic biopsy specimens, and their cumulative survival rate was significantly higher than that of the 28 REG-negative patients (P = 0.0073). Univariate analysis showed REG I expression to be a prognostic factor (P = 0.0386) that increased the risk of death 8.4-fold.Conclusions Evaluation of REG I expression in untreated endoscopic biopsy specimens may provide a basis for new treatments of locally advanced thoracic squamous cell esophageal cancers.     

Open Versus Thoracoscopic Esophagectomy in Patients with Esophageal Squamous Cell Carcinoma

Background

The impact of minimally invasive esophagectomy on patient prognosis, particularly disease-free survival (DFS), has not been well addressed. We compared the clinical outcomes of open and thoracoscopic esophagectomy in patients with esophageal squamous cell carcinoma (ESCC).

Methods

Sixty-three and 66 patients, nonrandomized, underwent open and thoracoscopic esophagectomies for ESCC between 2008 and 2011 were included. The clinicopathological data were reviewed retrospectively. Perioperative outcome, overall survival (OS), DFS, and the recurrence sites after open and thoracoscopic esophagectomy were compared.

Results

The open and thoracoscopic groups were comparable with regard to the total number of harvested lymph nodes and the percentage patients undergoing R0 resection. Fewer patients in the thoracoscopic group had pneumonia and wound complications. Intensive care unit (ICU) stay also was shorter in the thoracoscopic group. The recurrence pattern was similar in the two groups. In the open and thoracoscopic groups, the 3-year OS rates were 47.6 and 70.9 % (p = 0.031), respectively, and the 3-year DFS rates were 35 and 62.4 % (p = 0.007), respectively. However, the trends in better OS and DFS in the thoracoscopic group were not significant after stratification according to pathologic stage.

Conclusions

The perioperative benefit of thoracoscopic esophagectomy included fewer postoperative complications and shorter ICU stays. Mid-term OS and DFS associated with thoracoscopic techniques are at least equivalent to those associated with open procedures.     

Selective Lymphadenectomy for Salvage Esophagectomy in Patients with Esophageal Squamous Cell Carcinoma

Annals of Surgical Oncology - Extensive lymph node dissection increases the risk of postoperative complications, especially in salvage surgery, after definitive chemoradiotherapy (≥ 50 Gy) in...     

Abdominal Lymph Node Metastasis in Patients with Mid Thoracic Esophageal Squamous Cell Carcinoma

Background  There are few reports about abdominal lymph node metastasis of mid thoracic esophageal carcinoma. This study was designed to explore the pattern of abdominal lymph node metastasis in patients with mid thoracic esophageal squamous cell carcinoma and to evaluate the prognostic factors. Methods  The complete data of 368 patients with mid thoracic esophageal squamous cell carcinoma, who underwent modified Ivor-Lewis esophagectomy with two-field lymphadenectomy from January 1998 to January 2003, were reviewed. Survival rate was calculated by Kaplan-Meier method. Cox regression analysis was performed to identify risk prognostic factors. Results  Abdominal lymph node metastasis occurred in 58 (15.8%) patients: 34.5% (20/58) of them were stage T1 and T2. Skipping abdominal node metastasis was recognized in 13.8% (8/58) patients: all were stage T1 and T2. The overall 5-year survival rate of patients with abdominal lymph node metastasis (10.3%) was lower than that of those with thoracic node metastasis (18.3%). The prognosis of patients with distant abdominal lymph node metastasis was poor, and no one could survive more than 5 years. Cox regression analysis showed that five or more positive nodes and distant abdominal node metastasis were independent risk factors of patients with abdominal lymph node metastasis. Conclusions  Abdominal lymph node metastasis in patients with mid thoracic esophageal squamous cell carcinoma occurred frequently, and the surgery favorable for extensive abdominal lymph node dissection should be selected. The prognosis of patients with abdominal lymph node metastasis was poor, especially those with more positive nodes and distant abdominal node metastasis.     

Long-term Results after Dissection of Positive Thoracic Lymph Nodes in Patients with Esophageal Squamous Cell Carcinoma

Background Although thoracic lymph node metastasis in patients with thoracic esophageal squamous cell carcinoma (SCC) has been reported to be a negative risk factor for long-term survival, only a few studies have evaluated the clinicopathologic difference between the impact of metastasis to the paraesophageal lymph nodes and to the nonparaesophageal lymph nodes. The purpose of this study was to evaluate surgical outcome after the clearance of metastatic thoracic lymph nodes. Methods Retrospectively reviewed were 164 consecutive patients with thoracic esophageal SCC who had not had preoperative treatment and underwent surgery from 1980 to 2005 and were found to have thoracic lymph node metastases. Of these patients, 83 underwent surgery from 1980 to 1994 and 81 from 1995 to 2005. Univariate and multivariate analyses were performed to evaluate the impact of nonparaesophageal lymph node metastasis on survival. Results Univariate analysis revealed that T3/T4 tumors and the presence of nonparaesophageal node metastases were associated with only a 20% overall five-year survival rate. The overall five-year survival for the most recent period was significantly better than for the former period (42% vs. 13%, p < 0.01). Based on a multivariate analysis of prognostic impact of each nonparaesophageal node, the presence of metastatic subcarinal and/or posterior mediastinal nodes was an independent risk factor for reduced survival. Conclusion Surgical outcome for patients with thoracic esophageal cancer and metastatic thoracic lymph nodes has improved during the last 25 years. Although postoperative chemotherapy might improve survival, the presence of T3/T4 tumors and/or metastatic nonparaesophageal nodes were unfavorable factors for survival.     

A Randomized Trial Comparing Postoperative Adjuvant Chemotherapy with Cisplatin and 5-Fluorouracil Versus Preoperative Chemotherapy for Localized Advanced Squamous Cell Carcinoma of the Thoracic Esophagus (JCOG9907)

Background

Patients with esophageal carcinoma receiving postoperative chemotherapy showed superior disease-free survival than those receiving surgery alone in a Japan Clinical Oncology Group trial (JCOG9204). The purpose of this study was to evaluate optimal perioperative timing??that is, before or after surgery??for providing chemotherapy in patients with locally advanced esophageal squamous cell carcinoma.

Methods

Eligible patients with clinical stage II or III, excluding T4, squamous cell carcinoma were randomized to undergo surgery followed (group 1) or preceded (group 2) by chemotherapy consisting of two courses of cisplatin plus 5-fluorouracil. The primary end point was progression-free survival.

Results

We randomized 330 patients, with 166 assigned to group 1 and 164 to group 2, between May 2000 and May 2006. The planned interim analysis was conducted after completion of patient accrual. Progression-free survival did not reach the stopping boundary, but overall survival in group 2 was superior to that of group 1 (P?=?0.01). Therefore, the Data and Safety Monitoring Committee recommended early publication. Updated analyses showed the 5-year overall survival to be 43% in group 1 and 55% in group 2 (hazard ratio 0.73, 95% confidence interval 0.54?C0.99, P?=?0.04), where the median follow-up of censored patients was 61.6?months. Concerning operative morbidity, renal dysfunction after surgery in group 2 was slightly higher than in group 1.

Conclusions

Preoperative chemotherapy with cisplatin plus 5-fluorouracil can be regarded as standard treatment for patients with stage II/III squamous cell carcinoma.     

鳞状细胞癌抗原在食管癌临床的应用

采用微粒酶免疫荧光法测定了４０例食管癌和７例术后复发病人的血清鳞状细胞癌（ＳＣＣ）抗原含量，取２０例正常人，１５例食管良性病人和１５例腺癌病人作对照。结果表明，食管癌和术后复发病人的血清ＳＣＣ抗原含量显著高于正常人、良性病人和腺癌病人（Ｐ值分别＜０．００１、０．０１和０．０５），ＳＣＣ抗原与临床病期、细胞的分化程度有关。这提示血清ＳＣＣ抗原是食管癌理想的肿瘤标志物，对食管癌的诊断、预示术后复发和判断食管癌的恶性程度都有重要的临床价值。     

Improved Surgical Results in Thoracic Esophageal Squamous Cell Carcinoma: A 40-year Analysis of 792 Patients

Extensive lymphadenectomy, including upper mediastinum, for thoracic esophageal carcinoma was introduced at the beginning of 1980s. However, the efficacy has not been analyzed in large series at a single institute. We evaluated factors potentially related to improved surgical results in patients with thoracic esophageal squamous cell carcinoma (SCC). From 1959 to 1998, a total of 792 patients with thoracic esophageal SCC underwent R0 surgery. A variety of clinicopathological factors were compared among patients treated from 1990 to 1998 (recent group, n = 164) and 1959 to 1989 (former group, n = 628). The recent group showed significantly better survival than the former group (5-year survival rates: 51 versus 17%, P < 0.01), partly because earlier stage disease was included in the recent group than in the former group. Multivariable analysis, using the Cox regression analysis, indicated the time period of surgery, age, tumor location, the number of positive nodes (>5), venous invasion, and tumor–node–metastasis stage. Upper mediastinum lymphadenectomy was also an independent factor to improve survival of patients with thoracic esophageal SCC. Based on multivariate analysis of 792 cases during 40-years experience on thoracic esophageal cancer surgery at Chiba University Hospital, upper mediastinum lymphadenectomy was found to be one of the independent prognostic factors to improve patient’s overall survival.     

食管鳞癌RASSF1A基因启动子区甲基化研究

目的 研究肿瘤抑制基因RASSF1A启动子区甲基化所致该基因表达抑制在我国食管鳞癌发生中的作用及可能机制. 方法 用甲基化特异PCR技术(MSP)检测43例原发性食管鳞癌标本及6例对照食管上皮组织标本、食管鳞癌细胞系TE11和TE12中RASSF1A启动子甲基化状态;逆转录(RT)-PCR法检测5-氮-2′-脱氧胞苷(5-Aza-CdR)处理前后食管鳞癌细胞系中RASSF1A mRNA表达水平;Western blot方法检测食管鳞癌细胞系中细胞微管蛋白的表达. 结果 20.9%(9/43)原发性食管鳞癌标本有RASSF1A启动子超甲基化,正常食管上皮组织未发现该基因超甲基化改变.RASSF1A基因甲基化与食管癌患者的性别和TNM分期无关(P＞0.05),但在不同年龄组间的差异有统计学意义(P＜0.05).TE12细胞RASSF1A启动子发生甲基化,RT-PCR检测不到RASSF1A mRNA.TE11细胞系启动子未发生甲基化,RT-PCR检测其有RASSF1A mRNA表达.5-Aza-CdR处理可使TE12重新表达RASSF1A mRNA.TE12细胞的β-微管蛋白水平比TE11细胞低87.8%. 结论 原发性食管鳞癌存在RASSF1A启动子超甲基化,该基因甲基化与年龄相关.RASSF1A在食管鳞癌细胞系表达抑制与其甲基化状态有关.RASSF1A表达缺失可能导致β-微管蛋白减少.     

Association of Clinical and Dosimetric Factors with Postoperative Pulmonary Complications in Esophageal Cancer Patients Receiving Intensity-Modulated Radiation Therapy and Concurrent Chemotherapy Followed by Thoracic Esophagectomy

Background  To investigate the association between clinical/dosimetric factors and postoperative pulmonary complications (PPC) in esophageal cancer patients undergoing neoadjuvant chemotherapy and intensity-modulated radiation therapy (IMRT) followed by thoracic esophagectomy. Methods  The data from 52 patients receiving combined modality treatment were analyzed. Chemotherapy was taxane-based in 43 and 5-fluorouracil-based in 9 patients. IMRT (40–45 Gy, median 40 Gy, at 1.8–2 Gy per fraction) was given using a 3–5-beam arrangement. Surgery consisted of open or minimally invasive esophagectomy. The dosimetric parameters were generated from lung dose-volume histogram computed by the treatment planning software. PPC was defined as pneumonia or respiratory insufficiency within 30 days after surgery. Statistical correlations were analyzed between clinical/dosimetric factors and PPC. Results  The incidence of PPC was 34.6%. No patients died of PPC. Two patients (3.8%) became ventilator dependent. In univariate analyses, preoperative forced expiratory volume in 1 s (FEV1) and forced vital capacity before surgery were significantly associated with PPC (P = 0.02 and 0.04, respectively). None of the dosimetric factors predicted development of PPC. For the 51 patients undergoing right transthoracic surgery, higher absolute spared volume of the right lung receiving 15 Gy was significantly associated with PPC (P = 0.03). In multivariate analysis, preoperative FEV1 was the only independent factor associated with PPC (P = 0.002). Conclusions  Preoperative rather than prechemoradiation FEV1 predicts development of PPC. Reducing the absolute volume of the right lung that is irradiated might decrease the risk of PPC for patients receiving right transthoracic surgery.     

Body Mass Index and Survival in Esophageal Adenocarcinoma Treated with Chemoradiotherapy Followed by Esophagectomy

Background

Body mass index (BMI) has been linked with inferior outcomes in gastrointestinal malignancies. The purpose of this study is to evaluate the effect of BMI on survival in patients with esophageal adenocarcinoma.

Methods

Medical records were analyzed for patients who underwent esophagectomy after neoadjuvant chemoradiotherapy (nCRT) for adenocarcinoma from 2000 to the present. Patients were grouped into BMI ??25, >25?C30, >30?C35, and BMI >35. Overall survival (OS) and disease-free survival (DFS) were analyzed using the Kaplan?CMeier method. Multivariate analysis (MVA) was performed using Cox proportional hazard regression model.

Results

We identified 303 patients for the analysis. The only difference in patient characteristics between groups was gender. We found no difference in OS and DFS associated with BMI (p?=?0.3297 for OS; p?=?0.5950 for DFS). There were no differences in postoperative complications or mortality between BMI groups. MVA revealed that higher stage and less than a complete response to nCRT were prognostic for worse OS and DFS, while age, gender, type of surgery, year of diagnosis, and BMI were not prognostic.

Conclusions

BMI was neither associated with surgical complications nor survival in patients with esophageal adenocarcinoma treated with nCRT. BMI should not be considered a contraindication to surgical resection after nCRT.     

Thoracic Duct Resection During Esophagectomy Does Not Contribute to Improved Prognosis in Esophageal Squamous Cell Carcinoma: A Propensity Score Matched-Cohort Study

Purpose

Esophagectomy with extended lymphadenectomy remains the mainstay of treatment for localized esophageal squamous cell carcinoma (ESCC). Thoracic duct (TD) resection has been recommended as part of extended lymphadenectomy, although its merits are unclear. The aim of this two-institutional, matched-cohort study is to clarify whether TD resection improves prognosis in esophagectomy for ESCC.

Patients and Methods

In this two-institutional, matched-cohort study of 399 patients with ESCC who underwent McKeown esophagectomy between 2010 and 2014, the primary outcomes were overall survival (OS), disease-free survival (DFS), and cause-specific survival (CSS). Secondary outcomes were perioperative results and recurrence patterns.

Results

Based on a propensity score, 122 TD-resected or 122 TD-preserved patients in all stages were selected (median follow-up 4.5 years). The 5-year OS, DFS, and CSS rates in the TD-resected versus TD-preserved groups were 49% versus 60%, 53% versus 57%, and 58% versus 70%, respectively, without any significant differences. Operative time for the thoracic procedure was significantly longer and the number of retrieved mediastinal nodes was significantly higher in the TD-resected group (P = 0.009 and 0.005, respectively). The rates of chylothorax and left recurrent laryngeal nerve (RLN) palsy were significantly higher in the TD-resected group (P = 0.041 and 0.018, respectively). There were no significant differences in rates of local or distant metastases between the two groups.

Conclusions

TD resection does not contribute to improve OS, DFS, or CSS in ESCC but increases incidence of chylothorax and left RLN palsy. Prophylactic TD resection should be avoided in esophagectomy for ESCC.

     

Clinical Significance of SIP1 and E-cadherin in Patients with Esophageal Squamous Cell Carcinoma

Annals of Surgical Oncology - Epithelial-mesenchymal transition (EMT), when epithelial cells convert to mesenchymal cells, influences cancer invasion and metastasis. Smad interacting protein 1...     

Impact of Examined Lymph Node Count for Esophageal Squamous Cell Carcinoma in Patients who Underwent Right Transthoracic Esophagectomy

Annals of Surgical Oncology - The impact of the number of examined lymph nodes (ELNs) on stage correction and prognostication in patients with esophageal squamous cell carcinoma (ESCC) who...     

Prognostic Significance of NBS1 and Snail Expression in Esophageal Squamous Cell Carcinoma

Background

Esophageal squamous cell carcinoma (ESCC) is a lethal malignancy, but only limited molecular markers can predict its prognosis. Recently, a DNA double-strand break repair protein Nijmegen breakage syndrome 1 (NBS1) was reported to induce Snail expression and predict poor prognosis in head and neck cancers. However, the clinicopathologic roles of NBS1 and Snail in ESCC remain unclear.

Methods

From January 1995 to September 1999, tissue samples from 153 patients with ESCC who underwent esophagectomies at our institutions were collected and made into tissue core arrays for study. Expression of NBS1 and Snail was examined by immunohistochemical staining. The clinicopathologic data were analyzed, and some additional studies were performed to explore the relationship between NBS1 and Snail.

Results

NBS1 overexpression was observed in 28.1% (43/153) of ESCC, whereas Snail overexpression was observed in 26.1% (40/153) of ESCC. Overexpression of NBS1 correlated inversely with nodal status (P = 0.009) and was associated with better overall survival (P = 0.002). On the other hand, overexpression of Snail correlated positively with lymphovascular invasion (P = 0.034) and was associated with worse overall survival (P = 0.036). Meanwhile, NBS1 overexpression correlated inversely with Snail overexpression marginally (P = 0.084). Using the Cox regression analysis, T status (P = 0.006), M status (P = 0.008), and NBS1 overexpression (P = 0.007) were the independent factors of overall survival.

Conclusions

Our results showed that NBS1 overexpression was an independent factor of better survival and Snail overexpression predicted a worse survival in ESCC. Combination of NBS1 plus Snail expression status could be used as a predictor of prognosis in ESCC.

     

Expression of Receptor for Advanced Glycation End Products (RAGE) is Related to Prognosis in Patients with Esophageal Squamous Cell Carcinoma

The receptor for advanced glycation end products (RAGE), known as a multiligand receptor for certain stress-associated factors, has been considered to affect the characteristic differences of various cancer cells. We analyzed the expression and clinicopathological significance of RAGE in esophageal squamous cell carcinoma. We investigated immunohistochemically the relationship between RAGE expression and clinicopathological factors, including prognosis, in surgical specimens of primary tumors in 216 patients with esophageal squamous cell carcinoma. Prognostic factors were examined by univariate and multivariate analyses (Cox proportional hazard regression model). The positive expression rate of RAGE was 50%. RAGE expression was negatively correlated with depth of invasion and venous invasion. Moreover, tumors with positive RAGE expression exhibited better prognosis than those with negative RAGE expression (5-year survival, 52% vs. 32%, respectively). Multivariate analysis indicated that the positive expression of RAGE was an independent prognostic factor, along with tumor depth and nodal metastasis. Our findings suggest that loss of RAGE expression may play an important role in the progression of esophageal squamous cell carcinoma. Evaluation of the expression of RAGE could be useful for determining the tumor properties, including those associated with prognosis, in patients with esophageal squamous cell carcinoma.     

Survival Prediction Capabilities of Preoperative Inflammatory and Nutritional Status in Esophageal Squamous Cell Carcinoma Patients

World Journal of Surgery - Studies have revealed the impacts of various inflammatory and nutritional markers in patients with esophageal squamous cell carcinoma (ESCC). We evaluated the prognostic...