Iron intake and markers of iron status and risk of Barrett’s esophagus and esophageal adenocarcinoma

Objective  

To investigate the association between iron intake and iron status with Barrett’s esophagus (BE) and esophageal adenocarcinoma (EAC).     

Management and prognosis of esophageal cancers: Has progress been made?

The aim of this study was to investigate time trends in treatment and prognosis of esophageal cancer in a well-defined French population. Data was obtained from the Burgundy Cancer Registry (France) and three time periods were defined: 1976-90, 1991-96 and 1997-2002. A logistic regression was used to identify factors associated with an R0 resection. A multivariate survival analysis was performed using a Cox model. From 1976 to 2002, 2267 patients were included. The R0 resection rate slightly increased from 20.9% to 25.8% (P=0.019) then remained stable. Operative mortality decreased from 11.7% to 6.7% (NS). Age and subsite significantly influenced the rate of resection for cure whereas period had no effect. Chemotherapy alone was seldom used and radiotherapy alone dramatically dropped over time. Chemoradiation used as adjuvant treatment increased from 16.3% (1976-90) to 30.6% (1997-02) (P<0.001) and as sole treatment from 16.0% to 48.5% (P<0.001). The 3-year survival rates were respectively 10.1% and 9.7% (NS). Age and stage at diagnosis influenced the prognosis of esophageal cancer whereas time period and histology had no influence. This study claims that esophageal cancer remains a serious cancer problem and no improvement has been seen in the study population in France in its management over time.     

Overexpression of human β-defensin 2 promotes growth and invasion during esophageal carcinogenesis

Human β-defensin 2 (HBD-2) is an antimicrobial peptide produced by mucosal surfaces in response to microbial exposure or inflammatory cytokines. Although HBD-2 is expressed in the esophagus in response to stress and infectious agents, little is known regarding its expression and functional role in esophageal carcinogenesis. In the current investigation, normal esophagus and N-nitrosomethylbenzylamine (NMBA)-induced precancerous and papillomatous lesions of the rat esophagus were characterized for HBD-2 encoding gene Defb4 and protein. HBD-2 was found to be overexpressed in esophagi of rats treated with NMBA compared to animals in control group. Results of Real-time PCR, Western blot and immunohistochemistry demonstrated a positive correlation between the overexpression of HBD-2 and the progression of rat squamous cell carcinogenesis (SCC) in the esophagus. We also observed that HBD-2 is overexpressed in tumor tissues removed from patients with esophageal SCC. Moreover, Defb4 silencing in vitro suppresses the tumor cell proliferation, mobility and invasion in esophageal SCC cell line KYSE-150. The results from this study provide experimental evidence that HBD-2 may play an oncogenic role in the initiation and progression of esophageal SCC and thus serves as a target for chemopreventive and therapeutic interventions.     

Combined modality therapy of esophageal cancer--standard of care?

Because of the controversies and conflicting data described above, it is very difficult to provide strict guidelines for the treatment of patients with locoregional esophageal carcinoma. It is necessary, however, to try to put current knowledge in perspective. Surgery remains a standard of care for potentially resectable disease. Definitive chemoradiation is a standard of care for locoregional disease, particularly if a patient is medically unfit for surgery, if a surgeon experienced in esophagectomies is unavailable, or if the patient has cervical disease, which would require very extensive surgery. Chemoradiation is superior to radiation alone for these patients. Some frail patients may only be able to tolerate palliative radiation. Preoperative chemotherapy is controversial, with two large randomized studies resulting in two different conclusions regarding survival benefit. NCCN guidelines do not suggest this modality as a standard of care. After assessment of the patient's tumor stage, performance status, and personal wishes for aggressive treatment, it is possible that some physicians may consider offering this option to patients. The patient should have advanced disease, an excellent performance status, and understand the controversies and lack of consensus about this option. Preoperative chemoradiation is controversial. Only one of three randomized trials showed a clear survival benefit; however, the patients treated with surgery alone in that trial had an unusually poor outcome. The second trial showed no benefit, and the third trial was negative but statistically powered only to reveal a large survival difference and in multivariate analysis showed a possible trend to improved outcome. The NCCN guidelines do not advocate preoperative chemoradiation as a standard of care. As stated above, however, some physicians may consider offering this option to patients with advanced disease, excellent performance status, and who understand the controversies and lack of consensus about this option. Patients with adenocarcinoma of the GE junction treated with surgery alone should have postoperative chemoradiation, particularly if there is tumor involvement in the lymph nodes. No definitive trial has been performed to determine whether chemoradiation plus surgery is superior to chemoradiation alone.     

Clinical pathology analysis of esophageal sarcomatoid carcinoma

Objective: The purpose of this study was to study the clinical, imaging characters and pathological characteristics of esophageal sarcomatoid carcinoma. Methods: We reviewed 23 cases of esophageal sarcomatoid carcinoma from Janu-ary 2006 to December 2013 in four hospitals. The data of patients who were esophageal sarcomatoid carcinoma operated were retrospectively analyzed. Al cases had completed upper gastrointestinal barium images materials and 14 of these cases had completed CT images materials. Upper gastrointestinal barium images and CT imaging features include tumor location, size, shape, and strengthen, etc. The biological parameters of lesions including the express of cytokeratin AE1/AE3, 34βE12, p63, Vimentin, desmin, Actin, S-100 and Ki-67 detected by immunhistochemical UltraSensitiveTM S-P method (n=23), and the patients’ data of contrastographic picture (n=23), imaging characters of CT scan (n=14), and their relationship were studied. Results:Upper gastrointestinal barium images, CT imaging and gastrointestinal fiberscopy revealed lobulated intraluminal fil ing defect 0.4 cm to 5.7 cm × 3.5 cm × 1.3 cm (mean=3. 7 cm) in the mid (n=14), lower (n=7) and upper (n=2) intrathoracic esophagus. Among 23 cases of esophageal sarcomatoid carcinoma, 19 patients were of mushroom type, 2 patients was of ulcer type, and 2 patients were of medul a type;19 patients were pedunculated, and 4 patients were no pedunculated (2 patients was of ulcer type). The tumor surface was relatively smooth and esophageal compliance was maintained. The pathological changes of esophagus such as lightly locked, rigid wal no-manifest partly, esophageal lumens expand partly, major fil ing sublobe defect could be shown through contrast medium. Normal esophagus was no unpack obviously over pathological changes. Enhanced computed tomography showed tumors in the intrathoracic esophagus and 8 lymph nodes metastases in 3 cases. Histological y, carcinomatous and sarcomatous components coexist. Microscopical y, the tumor comprised poorly dif erentiated squamous cellcarcinoma and spindle-shaped cells resembling leiomyosarcoma. Immu-nohistochemical y, spindle-shaped sarcomatous cells displayed weekly positive reaction to cytokeratin AE1/AE3. Transitional zone was seen between sarcomatous and carcinomatous elements in 5 cases. The 17 lymph nodes metastases in 5 cases (53 lymph nodes) among 23 cases esophageal sarcomatoid carcinoma (187 lymph nodes) were observed. Conclusion:The clinical and radiologic features of esophageal sarcomatoid carcinoma overlap with those of other esophageal neoplasms. There are the radiologic imaging changes such as a large, intraluminal, polypoid mass, major fil ing sublobe defect and pedicle skin flap tumor in esophageal lumen, esophageal lumen extension partly, dissepiment rigidity wal no obviously, etc. Histological y, carcinomatous and sarcomatous components coexist and the biphasic pattern is the key diagnostic feature. However, esophageal sarcomatoid carcinoma has a more favorable prognosis than other malignant esophageal neoplasms. Immunohistochemical staining seems necessary to distinguish these lesions from other esophageal neoplasms.     

Current trends in multimodality treatment of esophageal and gastroesophageal junction cancer – Review article

Purpose

Multimodality treatment has now been widely introduced in the curatively intended treatment of esophageal and gastroesophageal junction cancer. We aim to give an overview of the scientific evidence for the available treatment strategies and to describe which trends that are currently developing.

Targeted agents and esophageal cancer--the next step?

Esophageal cancer (EC) is an aggressive cancer and is a leading cause of cancer-related death worldwide. In the United States and Western Europe, there has been a decline in the incidence of squamous cell carcinomas coupled with a rapid rise in incidence of adenocarcinoma of the esophagus and gastroesophageal junction. Although the 5-year survival rates have slowly increased over time from 4% to 14%, the outcomes are still dismal. The lack of adequate preventative strategies, inadequate screening techniques, early lymphatic and hematogenous spread, and lack of truly effective therapeutic agents all contribute to the poor outcome. This review will highlight the current status of targeted therapies in EC. This will include a review of agents targeting the vascular endothelial growth factor and epidermal growth factor receptor pathways and trials planned or ongoing to incorporate these and other agents into therapy for advanced disease and into combined modality therapy for early-stage tumors. Further work is required regarding the rational integration of these targeted agents and the optimal selection of patients who will most likely benefit.     

Three cases of the malignant esophageal stenosis successfully treated with the Niti-S™ esophageal stent

We herein report three cases of the malignant esophageal stenosis successfully treated with the Niti-S? esophageal stent. CASE 1: The hilar lung cancer and its mediastinal lymph node metastasis pressed the esophagus extramurally and caused the marked stenosis. CASE 2: A metastatic lymph node along the left laryngeal nerve caused the stenosis of the trachea. A primary esophageal lesion located at the middle thoracic esophagus also caused the marked stenosis. At first, tracheal stent was placed because of dyspnea, and two weeks later, we placed an esophageal stent. Case 3: Esophageal cancer at lower thoracic esophagus after definitive radiation therapy caused the marked stenosis. Because of the stenosis of esophago-gastric junction( EGJ), we used an esophageal stent with a long cover in order to prevent a reflux into the esophagus. This new Niti-STM esophageal stent was easy to place at the stenosis without difficulty using a conventional device. The symptom was improved immediately for each case. We hope this new device will be used widely.     

Glycemic index, carbohydrate and fiber intakes and risk of reflux esophagitis, Barrett’s esophagus, and esophageal adenocarcinoma

Objective  To examine the association between dietary glycemic index (GI), glycemic load (GL), total carbohydrate, sugars, starch, and fiber intakes and the risk of reflux esophagitis, Barrett’s esophagus, and esophageal adenocarcinoma. Methods  In an all-Ireland study, dietary information was collected from patients with esophageal adenocarcinoma (n = 224), long-segment Barrett’s esophagus (n = 220), reflux esophagitis (n = 219), and population-based controls (n = 256). Multiple logistic regression analysis examined the association between dietary variables and disease risk by tertiles of intake and as continuous variables, while adjusting for potential confounders. Results  Reflux esophagitis risk was positively associated with starch intake and negatively associated with sugar intake. Barrett’s esophagus risk was significantly reduced in people in the highest versus the lowest tertile of fiber intake (OR 0.44 95%CI 0.25–0.80). Fiber intake was also associated with a reduced risk of esophageal adenocarcinoma, as was total carbohydrate intake (OR 0.45 95%CI 0.33–0.61 per 50 g/d increase). However, an increased esophageal adenocarcinoma risk was detected per 10 unit increase in GI intake (OR 1.42 95%CI 1.07–1.89). Conclusions  Our findings suggest that fiber intake is inversely associated with Barrett’s esophagus and esophageal adenocarcinoma risk. Esophageal adenocarcinoma risk is inversely associated with total carbohydrate consumption but positively associated with high GI intakes.     

Clinicopathological and prognostic role of MMP-9 in esophageal squamous cell carcinoma： a meta-analysis

Objective： Many studies reported that matrix metalloproteinase-9 （MMP-9） participated in the development of esophageal squamous cell carcinoma （ESCC） and resulted in poor prognosis, however, they all included few patients and had inconsistent results. So we conducted a meta-analysis to explore the correlation between overexpression of MMP-9 and the clinicopathological characteristics and overall survival （OS） of ESCC. Methods： PubMed, EMBASE, Web of Science, Chinese Biomedical Literature Database, Google Scholar and other databases were searched for relevant studies. The Newcastle-Ottawa quality assessment scale was used to assess the methodological quality of included study and RevMan 5.2 software was used to conduct meta-analysis. Results： A total of 35 studies were included, and the results of meta-analysis showed that overexpression of MMP-9 was associated with grade of differentiation [well/moderate vs. poor： odds ratio （OR）： 0.39, 95% confidence interval （CI）： 0.29-0.52; P〈0.00001], lymph node metastasis （negative vs. positive： OR： 0.24, 95% CI： 0.16-0.34; P〈0.00001）, TNM stage （T1/T2 vs. T3/T4： OR： 0.28, 95% CI： 0.14-0.54; P=0.0002）, the depth of invasion （T1/T2 vs. T3/T4： OR： 0.29, 95% CI： 0.17-0.49; P〈0.00001）, and vascular invasion of ESCC （negative vs. positive： OR： 0.35, 95% CI： 0.21-0.58; P〈0.0001）, and also associated with poor overall survival ofESCC （HR： 2.17, 95% CI： 1.32-3.57; P=0.002）. Subgroup analysis showed that more than 10% of carcinoma cell staining was associated with significant increase of mortality risk （HR： 2.44, 95 % CI： 1.16-5.15; P=0.02）, and sensitive analysis suggested that MMP-9 was an independent prognostic factor in ESCC （HR： 1.49, 95% CI： 1.16-1.91; P=0.002）. Conclusions：On the basis of limited evidence, overexpression of MMP-9 may be a potential independent prognosis factor of ESCC patients in Asia, and high-quality studies assessing the prognostic significance of MMP-9 for ESCC patients are still needed.     

Change of HER2 status in metastatic esophageal adenocarcinoma: heterogeneity of the disease? Case report and review of literature

A case report is presented of a patient diagnosed with esophageal adenocarcinoma with an extremely aggressive clinical course. Discordant expression of HER2 in longitudinally-collected biopsies was noted, with the original biopsy testing negative and a follow up biopsy testing positive. Upon retest of the original biopsy however, heterogeneity of HER2 expression was found among tumor clones across three distinct fields. The patient did not survive long enough to receive chemotherapy with trastuzumab, which has shown efficacy in tumors with HER2 positive expression. Understanding of the biological heterogeneity of HER2 expression in the primary tumor is crucial to detect HER2 positive clones, which may yield improved patient outcomes.Key Words: HER2, metastatic esophageal adenocarcinoma     

Different patterns of NF-κB and Notch1 signaling contribute to tumor-induced lymphangiogenesis of esophageal squamous cell carcinoma

Background

Lymph node involvement and tumor-induced lymphangiogenesis appear as the earliest features of esophageal squamous cell carcinoma (ESCC), although the molecular regulatory mechanisms involved have remained unclear. Our aim was to investigate the contribution of NF-κB and Notch1 signaling to lymph node involvement and tumor-induced lymphangiogenesis in ESCC.

Material and methods

NF-κB and Notch1 expression in 60 tissue samples of ESCC were assessed by immunohistochemical staining. The correlations of NF-κB and Notch1 with lymph node involvement, lymphatic vessel density (LVD), podoplanin, and vascular endothelial growth factor-C (VEGF-C) were further evaluated to determine the association of NF-κB and Notch1 expression with tumor-induced lymphangiogenesis.

Results

Chi-square tests revealed that NF-κB and Notch1 expression in ESCC tissues were significant associated with lymph node metastasis, LVD, podoplanin, and VEGF-C expression. Strong expression of NF-κB, but weak expression of Notch1, was observed in tumor tissues with lymph nodes involvement (P < 0.05 for both). The mean histoscores of LVD, podoplanin, and VEGF-C staining were higher in high-NF-κB-expressing tissue than in low-expressing tissue (P < 0.05 for each). In contrast, the mean histoscores of LVD and VEGF-C staining were lower in high-Notch1-expressing tissue than in low-expressing tissue (P < 0.05 for both). A multiple factors analysis of LVD and VEGF-C further demonstrated that LVD and VEGF-C status were significantly correlated with NF-κB and Notch1 expression in tumors. NF-κB and Notch1 expression were also significantly inversely correlated (P < 0.05).

Conclusion

These results suggest that different patterns of NF-κB and Notch1 signaling contribute to lymph nodes metastasis and tumor-induced lymphangiogenesis of ESCC, and reveal that up-regulation of NF-κB is associated with down-regulation of Notch1 in tumor tissue.     

Staging of esophageal carcinoma: Length of tumor and number of involved regional lymph nodes. Are these independent prognostic factors?

BACKGROUND AND OBJECTIVES: New potential prognostic indicators aside from the TNM classification have been proposed. The aim of this study was to analyze the prognostic relevance of tumor length as well as number of involved regional lymph nodes (LNM) in patients with esophageal carcinoma. METHODS: Two hundred thirteen patients with esophageal carcinoma (116 squamous cell- and 97 adenocarcinoma) were included in this study. Treatment of choice was subtotal en bloc esophagectomy including "2-field" lymphadenectomy. The median number of examined lymph nodes (LNs) was 28. Eighty patients (38%) received preoperative radio-chemotherapy according to a standardized protocol. Histopathology consisted of tumor stage, residual tumor, grading, and number of examined and involved LN. Univariate and multivariate prognostic values were calculated. RESULTS: Length of tumor correlated with pT/ypT-category (P<0.01). Univariate but not multivariate analysis showed better survival for tumors相似文献   

Phase II trial of sequential paclitaxel and 1 h infusion of bryostatin-1 in patients with advanced esophageal cancer

BACKGROUND: We sought to determine the response rate and toxicity profile of sequential paclitaxel and bryostatin-1, a novel, selective inhibitor of protein kinase C, in patients with advanced esophageal cancer. PATIENTS AND METHODS: Patients with advanced esophageal and gastroesophageal junction cancer were enrolled. All gave informed consent. They were initially treated with paclitaxel 90 mg/m(2) intravenously on Day 1 and bryostatin-1 50 mug/m(2) on Day 2 weekly for three consecutive weeks out of four. Because of severe myalgias, dosing was reduced to paclitaxel 80 mg/m(2) with bryostatin-1 40 mug/m(2) and then to paclitaxel 80 mg/m(2) with bryostatin-1 25 mug/m(2). RESULTS: Twenty-four patients were enrolled, with 22 assessable for response. The partial response rate was 27%. 10 patients treated with bryostatin-1 40-50 mug/m(2) had a response rate of 40 versus 17% at bryostatin-1 25 mug/m(2) (p-value = 0.3). Median time-to-progression was 3.7 months and median survival was 8.3 months. Grade 3/4 myalgias were seen in 50% of patients. Myalgias appeared to be related to bryostatin-1 dose. Because of toxicity, the trial was closed prior to full accrual. CONCLUSIONS: Despite potential anti-tumor activity of this combination in patients with advanced esophageal cancer, further development is not warranted, given the severe toxicity, especially myalgias, that were seen.     

Prospective study of serum retinol, β-carotene, β-cryptoxanthin, and lutein/zeaxanthin and esophageal and gastric cancers in China

Objective: This study examined the relationship between pretrial serum concentrations of retinol, -carotene, -cryptoxanthin, and lutein/zeaxanthin and the subsequent risk of developing esophageal squamous cell carcinoma and gastric cardia or non-cardia adenocarcinoma in subjects selected from a randomized nutritional intervention trial in Linxian, China, a region with epidemic rates of esophageal and gastric cardia cancer. Methods: We used a stratified case–cohort design to select cohort members for inclusion in this study. In all we measured serum concentrations of the above vitamins in 590 esophageal, 395 gastric cardia, and 87 gastric non-cardia case subjects as well as in 1053 control subjects. Relative risks (RRs) were estimated using Cox proportional hazards models. Results: Median values in our cohort were low for serum retinol (33.6 g/dl), -carotene (4.3 g/dl), and -cryptoxanthin (3.5 g/dl) , but were high for lutein/zeaxanthin (40.0 g/dl). Gastric cardia cancer incidence fell 10% for each quartile increase in serum retinol (RR = 0.90, 95% CI = 0.83–0.99). For esophageal cancer, an inverse association with retinol levels was found only in male non-smokers (RR = 0.79 per quartile increase, 95% CI = 0.63–0.99). For gastric non-cardia cancer, an inverse association was limited to subjects 50 years old or younger (RR = 0.58 per quartile, 95% CI = 0.31–0.96). For -cryptoxanthin there was a borderline significant protective association for gastric non-cardia cancer (RR = 0.88 per quartile, 95% CI = 0.76–1.0). In contrast, we found the incidence of gastric non-cardia cancer increased (RR = 1.2 per quartile, 95% CI = 1.0–1.3) with increasing concentration of serum lutein/zeaxanthin. Conclusions: In this population, we found that low retinol and high lutein/zeaxanthin concentrations increased the risks of gastric cardia and gastric non-cardia cancer respectively. We found that there were no strong associations between any of the other analytes and any of the cancer sites.     

Expressions of the γ_2 chain of laminin-5 and secreted protein acidic and rich in cysteine in esophageal squamous cell carcinoma and their relation to prognosis

Previous studies have shown that the expressions of the γ2 chain of laminin-5 and secreted protein acidic and rich in cysteine (SPARC) play important roles in oncogenesis and the development of carcinoma. To assess the expressions of laminin-5 γ2 chain and SPARC in esophageal squamous cell carcinoma (SCC), and to clarify the prognostic significance of the expressions of laminin-5 γ2 chain and SPARC in esophageal SCC, we detected the expressions of laminin-5 γ2 chain and SPARC in cancer tissue and correspond...