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Esophageal Carcinoma (esophageal + carcinoma)

Distribution by Scientific Domains
Medical Sciences100%

Kinds of Esophageal Carcinoma

  • thoracic esophageal carcinoma
    		•

    Selected Abstracts

    USEFUL ENDOSCOPIC ULTRASONOGRAPHY TO ASSESS THE EFFICACY OF NEOADJUVANT THERAPY FOR ADVANCED ESOPHAGEAL CARCINOMA: BASED ON THE RESPONSE EVALUATION CRITERIA IN SOLID TUMORS

    DIGESTIVE ENDOSCOPY, Issue 1 2005
    Masaho Ota
    Objective:, The aim of the present study was to assess the usefulness of endoscopic ultrasonography (EUS) for evaluating the efficacy of neoadjuvant therapy for advanced esophageal carcinoma based on the Response Evaluation Criteria in Solid Tumors (RECIST). Patients and Methods:, Sixty-two patients with advanced esophageal carcinoma underwent surgical resection after neoadjuvant therapy. The maximal tumor thickness was measured by EUS before and after neoadjuvant therapy, and the percent reduction was compared with the pathological response. Based on the RECIST, PD-SD (progressive disease-stable disease) was defined as < 30% reduction of tumor thickness on EUS, PR (partial response) as , 30% reduction of tumor thickness, and CR (complete response) as no detectable tumor (100%). Results:, The percent reduction of the thickness of Grade 0,1, Grade 2 and Grade 3 tumor was 11.5 ± 21.0%, 48.2 ± 17.0% and 74.9 ± 21.1%, respectively. There were significant differences in the extent of reduction among the three groups. Based on the RECIST, 80% of Grade 0,1 cases, 91% of Grade 2 cases and 22% of Grade 3 cases were PD-SD, PR, and CR according to EUS, respectively. EUS correctly identified 80% of non-responders and 94% of responders. Conclusions:, The percentage reduction of tumor thickness on EUS closely reflected the pathological evaluation. EUS evaluation based on the RECIST seems to be useful for monitoring neoadjuvant therapy in patients with esophageal carcinoma. [source]

    Esophageal cancer associated with right aortic arch: Report of two cases

    DISEASES OF THE ESOPHAGUS, Issue 4 2003
    H. Noguchi
    SUMMARY, Esophageal carcinoma associated with a right aortic arch is very rare. In such cases, the dissection of right paratracheal lymph nodes is difficult. Herein, we report two cases of thoracic esophageal carcinoma with right aortic arch, for which the left door open method was used to provide a good surgical view. Postoperative chemotherapy and radiotherapy were used for both cases and no evidence of recurrence or metastasis has been noted in the 24-month postoperative period. [source]

    USEFUL ENDOSCOPIC ULTRASONOGRAPHY TO ASSESS THE EFFICACY OF NEOADJUVANT THERAPY FOR ADVANCED ESOPHAGEAL CARCINOMA: BASED ON THE RESPONSE EVALUATION CRITERIA IN SOLID TUMORS

    DIGESTIVE ENDOSCOPY, Issue 1 2005
    Masaho Ota
    Objective:, The aim of the present study was to assess the usefulness of endoscopic ultrasonography (EUS) for evaluating the efficacy of neoadjuvant therapy for advanced esophageal carcinoma based on the Response Evaluation Criteria in Solid Tumors (RECIST). Patients and Methods:, Sixty-two patients with advanced esophageal carcinoma underwent surgical resection after neoadjuvant therapy. The maximal tumor thickness was measured by EUS before and after neoadjuvant therapy, and the percent reduction was compared with the pathological response. Based on the RECIST, PD-SD (progressive disease-stable disease) was defined as < 30% reduction of tumor thickness on EUS, PR (partial response) as , 30% reduction of tumor thickness, and CR (complete response) as no detectable tumor (100%). Results:, The percent reduction of the thickness of Grade 0,1, Grade 2 and Grade 3 tumor was 11.5 ± 21.0%, 48.2 ± 17.0% and 74.9 ± 21.1%, respectively. There were significant differences in the extent of reduction among the three groups. Based on the RECIST, 80% of Grade 0,1 cases, 91% of Grade 2 cases and 22% of Grade 3 cases were PD-SD, PR, and CR according to EUS, respectively. EUS correctly identified 80% of non-responders and 94% of responders. Conclusions:, The percentage reduction of tumor thickness on EUS closely reflected the pathological evaluation. EUS evaluation based on the RECIST seems to be useful for monitoring neoadjuvant therapy in patients with esophageal carcinoma. [source]

    Prospective non-randomized study of preoperative concurrent platinum plus 5-fluorouracil-based chemoradiotherapy with or without paclitaxel in esophageal cancer patients: long-term follow-up

    DISEASES OF THE ESOPHAGUS, Issue 2 2010
    M. Zemanova
    SUMMARY Combined modality treatment for esophageal carcinoma seems to improve survival over surgery alone. Different combinations of cytotoxic drugs have been studied to improve antitumor efficacy and limit the toxicity of chemoradiotherapy (CRT) with inconsistent results. We present a prospective study of neoadjuvant CRT with or without paclitaxel in chemotherapy schedule. One hundred seven patients (93 males, 14 females), median age 59 years (range 44,76), with operable esophageal cancer were enrolled. They received the following neoadjuvant therapy: Carboplatin, area under curve (AUC) = 6, intravenously on days 1 and 22, 5-fluorouracil (5-FU), 200 mg/m2/day, continuous infusion on days 1 to 42, radiation therapy 45 grays/25fractions/5 weeks beginning on day 1. Forty-four patients (41%) were furthermore non-randomly assigned to paclitaxel 200 mg/m2/3 h intravenously on days 1 and 22. Nutritional support from the beginning of the treatment was offered to all patients. Surgery was done within 4,8 weeks after completion of CRT, if feasible. All patients were evaluated for grade 3 plus 4 toxicities: leukopenia (28%), neutropenia (30%), anemia (6%), thrombocytopenia (31%), febrile neutropenia (6%), esophagitis (24%), nausea and vomiting (7%), pneumotoxicity (8%). Seventy-eight patients (73%) had surgery and 63 of them were completely resected. Twenty-two patients (20%) achieved pathological complete remission, and additional 20 (19%) had node-negative and esophageal wall-positive residual disease. There were 10 surgery-related deaths, mostly due to pulmonary insufficiency. Twenty-nine patients were not resected, 15 for early progression, 14 for medical reasons or patient refusal. After a median follow-up of 52 months (range 27,80), median survival of 18.0 months and 1-, 2-, 3- and 5-year survival of 56.7, 37.5, 27.0 and 21% was observed in the whole group of 107 patients. Addition of paclitaxel to carboplatin and continual infusion of FU significantly increased hematologic and non-hematologic toxicity, but treatment results as overall survival or time to progression did not differ significantly in groups with and without paclitaxel. Patients achieving pathological complete remission or nodes negativity after neoadjuvant therapy had favorable survival prognosis, whereas long-term prognosis of node positive patients was poor. Distant metastases prevailed as a cause of the treatment failure. Factors significant for survival prognosis in multivariate analysis were postoperative node negativity, performance status, and grade of dysphagia. Addition of paclitaxel to carboplatin and continual FU significantly increased hematologic and non-hematologic toxicity without influencing efficacy of the treatment. This study confirmed improved prognosis of patients after achieving negativity of nodes. Distant metastases prevailed as cause of the treatment failure. Prospectively, it is important to look for a therapeutic combination with better systemic effect. [source]

    Selective dose escalation of chemoradiotherapy for locally advanced esophageal cancer

    DISEASES OF THE ESOPHAGUS, Issue 7 2008
    S. K. Seung
    SUMMARY., This phase II study assessed the use of concurrent continuous infusion of 5-fluorouracil and weekly carboplatin plus paclitaxel with selective radiation dose escalation for patients with localized esophageal cancer. Patients with esophageal carcinoma were staged by thoracic and abdominal computed tomography, endoscopic ultrasound, and positron emission tomography scans. Patients received a continuous infusion of 5-fluorouracil 225 mg/m2 on days 1 to 38 and intravenous paclitaxel 45 mg/m2 and carboplatin AUC 2 on days 1, 8, 15, 22, 29, and 36. Radiotherapy was delivered in 1.8-Gy fractions, 5 d/wk for 5.5 weeks. Six to 8 weeks after initial therapy, patients without metastatic progression but with a positive biopsy, or less than partial response received a 9-Gy boost with the same concurrent chemotherapy. Twenty-four patients were enrolled: 18 patients were enrolled initially; 6 additional patients were enrolled following a protocol amendment designed to reduce the esophagitis by adding the radioprotectant amifostine. Median follow-up was 30 months. Twenty (83%) patients had adenocarcinomas of the lower esophagus/gastroesophageal junction. Seventeen patients (81%) attained at least a partial response. Six patients received boost treatment. At 4 years, overall survival was 28%, cause-specific survival was 38%, locoregional control was 61%, and distant metastasis-free survival was 52%. Radiation delays ranged from 0 to 62 days (median, 8 d), primarily owing to esophagitis. In total, 28% of patients developed esophageal strictures requiring dilatations. There were no differences in esophageal strictures, local control, or survival with the addition of amifostine. [source]

    Analysis of micrometastatic disease in histologically negative lymph nodes of patients with adenocarcinoma of the distal esophagus or gastric cardia

    DISEASES OF THE ESOPHAGUS, Issue 6 2008
    C. J. Buskens
    SUMMARY., Lymphatic dissemination is the most important prognostic factor in patients with esophageal carcinoma. However, the clinical significance of lymph node micrometastases is still debated due to contradictory results. The aim of the present study was to identify the incidence of potentially relevant micrometastatic disease in patients with histologically node-negative esophageal adenocarcinoma and to analyze the sensitivity and specificity of three different immunohistochemical assays. From a consecutive series of 79 patients who underwent a transthoracic resection with extended 2-field lymphadenectomy, all 20 patients with pN0 esophageal adenocarcinoma were included in this study. A total of 578 lymph nodes were examined for the presence of micrometastases by immunohistochemical analysis with the antibodies Ber-EP4, AE1/AE3 and CAM 5.2. Lymph node micrometastases were detected in five of the 20 patients (25%). They were identified in 16 of the 578 lymph nodes examined (2.8%) and most frequently detected with the Ber-EP4 and AE1/AE3 antibody (sensitivity 95% and 79% respectively). In 114 of the 559 negative lymph nodes (20.4%), positive single cells were found that did not demonstrate malignant characteristics. These false-positive cells were more frequently found with the AE1/AE3 staining (specificity of the Ber-Ep4 and AE1/AE3 antibody 94% and 84% respectively). The presence of nodal micrometastases was associated with the development of locoregional recurrences (P=0.01), distant metastases (P=0.01), and a reduced overall survival (log rank test, P=0.009). For the detection of clinically relevant micrometastatic disease in patients operated upon for adenocarcinoma of the distal esophagus or gastric cardia, Ber-EP4 is the antibody of first choice because of its high sensitivity and specificity. Immunohistochemically detected micrometastases in histologically negative lymph nodes have potential prognostic significance and are associated with a high incidence of both locoregional and systemic recurrence. Therefore, this technique has the potential to refine the staging system for esophageal cancer and to help identify patients who will not be cured by surgery alone. [source]

    Estrogen and progesterone receptors in esophageal carcinoma

    DISEASES OF THE ESOPHAGUS, Issue 4 2008
    R. Kalayarasan
    SUMMARY., Information is sparse and contradictory in the literature regarding the role of estrogen receptor (ER) and progesterone receptor (PR) in esophageal carcinoma. This study was conducted over a period of 18 months from September 2004 with the primary aim of determining the PR, ER alpha (ER,) and ER beta (ER,) status of esophageal carcinoma and normal esophageal mucosa (NEM). The receptor status was correlated with tumor type, tumor differentiation and tumor stage. A total of 45 patients with histologically proven squamous cell carcinoma (SCC) (n = 30) and adenocarcinoma (AC) (n = 15) were studied. Receptor status was detected by immunohistochemistry (IHC) and semiquantitative assessment was done by quick score method of endoscopic biopsy specimens. The mean age for SCC and AC were not significantly different. The gender ratio in favor of males was 3 : 2 for SCC and 4 : 1 for AC. None of the specimens from SCC or AC showed positivity for PR both in NEM and tumor tissue. Likewise none of the specimens were positive for ER, by IHC. The mean ER, score for AC was significantly higher than SCC. For SCC it was seen that ER, positivity in tumor cells increases with dedifferentiation and increasing tumor stage. This trend was seen for AC as well. ER, is over-expressed in poorly differentiated SCC and AC compared to NEM. Thus ER, may be a marker for poor biological behavior, that is dedifferentiation or higher stage of disease. In view of these findings we propose a large-scale prospective, longitudinal interventional study using selective estrogen modulators. [source]

    Oxford experience with neoadjuvant chemotherapy and surgical resection for esophageal adenocarcinomas and squamous cell tumors

    DISEASES OF THE ESOPHAGUS, Issue 3 2008
    P. M. Safranek
    SUMMARY., The Medical Research Council trial for oesophageal cancer (OEO2) trial demonstrated a clear survival benefit from neoadjuvant chemotherapy in resectable esophageal carcinoma. Since February 2000 it has been our practice to offer this chemotherapy regime to patients with T2 and T3 or T1N1 tumors. We analyzed prospectively collected data of patients who received neoadjuvant chemotherapy prior to esophageal resection under the care of a single surgeon. Complications of treatment and overall outcomes were evaluated. A total of 194 patients had cisplatin and 5-fluorouracil prior to esophageal resection. Six patients (5.7%) had progressive disease and were inoperable (discovered in four at surgery). During chemotherapy one patient died and one perforated (operated immediately). Complications including severe neutropenia, coronary artery spasm, renal impairment and pulmonary edema led to the premature cessation of chemotherapy in 12 patients (6.2%). A total of 182 patients with a median age of 63 (range 30,80), 41 squamous and 141 adenocarcinomas underwent surgery. Operations were 91 left thoracoabdominal (50%), 45 radical transhiatal (25%), 40 Ivor-Lewis (22%) and six stage three (3%), and 78.6% had microscopically complete (R0) resections. Median survival was 28 months with 77.3% surviving for 1 year and 57.7% for 2 year. In hospital mortality was 5.5% and anastomotic leak rate 7.7%. A radical surgical approach to the primary tumor in combination with OEO2 neoadjuvant chemotherapy has led to a high R0 resection rate and good survival with acceptable morbidity and mortality. [source]

    Changes in antioxidant defense status in response to cisplatin and 5-FU in esophageal carcinoma

    DISEASES OF THE ESOPHAGUS, Issue 2 2008
    T. Kaur
    SUMMARY., The ability of reactive oxygen species to induce cellular damage and to cause cell death opens the possibility of exploiting this property in the treatment of esophageal cancer through a free radical mediated mechanism. The present study was carried out with the aim of evaluating the changes in the antioxidant defense status in esophageal cancer patients treated without and with neoadjuvant therapy (NAT). Forty surgically resected tissue specimens from tumors, tissue adjoining the tumors and paired macroscopically normal mucosa were obtained from esophageal cancer patients treated with or without chemo-radiotherapy. An evaluation of antioxidant defense system in the normal, adjoining and tumor esophageal tissues in response to NAT revealed decreased catalase activity in tumor and adjoining tissues as compared to their respective normal tissue levels. Similarly, decreased superoxide dismutase activity was observed in tumor tissue in response to NAT. In both the treatment groups (with and without NAT), no significant change was observed in the enzyme activity of glutathione reductase in the normal, adjoining and tumor tissues. Enhanced glutathione peroxidase activity was found in tumor tissue, as compared to the adjoining and paired normal tissue of patients after NAT. Estimation of reduced glutathione (GSH) levels showed a significant decline in GSH levels in esophageal tumors after NAT. Depletion of GSH, an endogenous antioxidant, would elevate drug sensitivity and might predispose neoplastic cells to apoptosis in response to NAT. The antioxidant enzymes in the esophageal carcinoma thus may play an important role in influencing the final outcome upon NAT course. [source]

    Reduction rate of lymph node metastasis as a significant prognostic factor in esophageal cancer patients treated with neoadjuvant chemoradiation therapy

    DISEASES OF THE ESOPHAGUS, Issue 2 2007
    S. Aiko
    SUMMARY., Tumor regression is used widely as a measure of tumor response following radiation therapy or chemoradiation therapy (CRT). In cases of esophageal cancer, a different pattern of tumor shrinkage is often observed between primary tumors and metastatic lymph nodes (MLNs). Regression of MLNs surrounded by normal tissue may be a more direct measure of the response to CRT than regression of a primary tumor as exfoliative mechanical clearance does not participate in shrinkage of MLNs. In this study we evaluated the significance of the reduction rate (RR) of MLNs as a prognostic factor in esophageal cancer patients treated with neoadjuvant CRT. Forty-two patients with marked MLNs were selected from 93 patients with esophageal carcinoma who had received neoadjuvant CRT. The RRs of the primary tumor and the MLNs were calculated from computed tomography scans. In 20 patients, surgical resection was carried out following CRT. Univariate analysis was used to determine which of the following variables were related to survival: size of the primary tumor and MLNs; RRs of both lesions; degree of lymph node (LN) metastasis; clinical stage; and surgical resection. Multivariate analysis was then performed to assess the prognostic relevance of each variable. The primary tumor was larger than the MLNs in 69% of patients before CRT and in 40% of patients after CRT. In 79% of the patients, the RR of the primary tumor was greater than the RR of the MLNs. The results of the univariate analyses showed that a high RR of the MLNs and surgical resection after CRT were associated with significantly improved survival. The multivariate analysis demonstrated that the RR of MLNs had the strongest influence on survival. The RR of LN metastasis should be evaluated as an important prognostic predictor in patients with marked LN metastasis of esophageal cancer treated with CRT. [source]

    HER-2 overexpression (3+) in patients with squamous cell esophageal carcinoma correlates with poorer survival

    DISEASES OF THE ESOPHAGUS, Issue 4 2006
    M. Dreilich
    SUMMARY., The incidence of esophageal carcinoma is increasing worldwide. In Sweden, approximately 400 patients are diagnosed each year. The present study retrospectively investigates survival in 97 patients with esophageal carcinoma in regard to their HER-2 status as examined by immunohistochemistry (IHC) and chromogen in situ hybridization (CISH). Sixty-eight patients had localised disease and 29 patients had advanced disease. Seventy patients had squamous cell carcinoma, and nine of these patients (13%) had HER-2 overexpression (3+). Eight (30%) of 27 adenocarcinoma patients overexpressed (3+) HER-2. In patients overexpressing (3+) HER-2 a statistical trend towards poorer survival was observed (P = 0.057). In squamous cell carcinoma patients, HER-2 overexpression (3+) correlated with poorer survival (P = 0.035), whereas in adenocarcinoma patients, HER-2 status (3+) did not. HER-2 amplification according to CISH was present in five (two squamous cell carcinomas and three adenocarcinomas) out of 17 HER-2 overexpressing (3+) tumours. In conclusion, HER-2 overexpression (3+) seems to be associated with poorer survival in esophageal carcinomas, especially in patients with squamous cell esophageal carcinoma. [source]

    Detection of human papillomavirus DNA in squamous cell carcinoma of the esophagus by auto-nested PCR

    DISEASES OF THE ESOPHAGUS, Issue 2 2006
    A. P. Souto Damin
    SUMMARY., The aim of the present study was to investigate the presence of human papillomavirus (HPV) in surgical specimens of esophageal squamous cell carcinoma. One hundred and sixty-five paraffin-embedded specimens of esophageal carcinoma were analyzed through high-sensitivity auto-nested polymerase chain reaction (PCR) using the consensus GP5+/GP6+ primer. Twenty-six specimens of esophageal mucosa without malignant disease were also studied as a control group. Two different specific primer sets targeting the E6 region of the HPVs 16 and 18 were used for typing. Direct DNA sequence analysis was conducted to confirm positive PCR results. HPV DNA was detected in 26 esophageal carcinomas (15.75%), but in none of the benign esophageal specimens (P < 0.05). Out of the 26 positive cases, 24 were HPV-16 and one was HPV-18. One tumor contained both HPV-16 and -18 DNA. Positive PCR results were confirmed by the amplified viral sequences. Our findings suggest that the presence of either HPV-16 or -18 might be related to development of the malignant phenotype in the esophagus. [source]

    Esophageal cancer associated with right aortic arch: Report of two cases

    DISEASES OF THE ESOPHAGUS, Issue 4 2003
    H. Noguchi
    SUMMARY, Esophageal carcinoma associated with a right aortic arch is very rare. In such cases, the dissection of right paratracheal lymph nodes is difficult. Herein, we report two cases of thoracic esophageal carcinoma with right aortic arch, for which the left door open method was used to provide a good surgical view. Postoperative chemotherapy and radiotherapy were used for both cases and no evidence of recurrence or metastasis has been noted in the 24-month postoperative period. [source]

    Clinical outcome and survival after esophagectomy for carcinoma in elderly patients

    DISEASES OF THE ESOPHAGUS, Issue 2 2003
    L. Bonavina
    SUMMARY Advances in perioperative management have allowed more and more elderly patients to undergo major surgery with postoperative morbidity and mortality rates comparable to those of younger individuals. The aim of this study was to evaluate the impact of age on the clinical outcome and long-term survival of patients with esophageal carcinoma undergoing esophagectomy. Nine-hundred patients with esophageal carcinoma were divided into two groups: A (n = 403) with age , 65 years, and B (n = 497) with age < 65 years. One-hundred and fifty three (38%) patients of group A underwent surgery compared to 272 (55%) of group B (P < 0.01). Postoperative mortality, and the prevalence of anastomotic leak and respiratory complications were similar in both groups; conversely, there was a higher prevalence of cardiovascular complications in group A (13%vs 3%, P < 0.01). Five-year survival was about 35% in both groups. In conclusion, advanced age should no longer be considered an absolute contraindication to esophagectomy for carcinoma in selected patients. In fact, the postoperative mortality and long-term survival rates of elderly patients undergoing resection are comparable to that of younger individuals. [source]

    Resection surgery with neoadjuvant chemoradiotherapy improves outcomes of patients with T4 esophageal carcinoma

    DISEASES OF THE ESOPHAGUS, Issue 2 2003
    T. Noguchi
    SUMMARY The prognosis of patients with T4 esophageal carcinoma is poor, and thus an effective treatment needs to be established. The present study assessed the effect of chemoradiotherapy (CRT), postoperative morbidity and mortality, and survival time in 41 patients with T4 esophageal carcinoma. Of these, 24 received CRT followed by surgery (group A) and the remaining 17 were treated with CRT alone (group B). Postoperative complications in group A were compared with 251 patients (group C) who underwent surgery without CRT during the same period. Postoperative complications were more frequent in group A than group C (29.2%vs 8.4%, P < 0.05). The overall median survival of group A was statistically longer than that of group B (13.8 months and 3.3 months respectively, P < 0.001). Complete histologic response (grade 3) was documented in 4 group A patients (16.7%). The overall median survival of grade 3 patients was statistically longer than the rest of group A (38.9 months vs 8.8 months, P < 0.05). The data confirm that chemoradiotherapy creates tumor regression in some patients and allows resection surgery in T4 esophageal carcinoma. Moreover, surgery with CRT confers a survival advantage in T4 esophageal carcinoma. [source]

    Aberrant subclavian artery causing difficulty in transhiatal esophageal dissection

    DISEASES OF THE ESOPHAGUS, Issue 2 2003
    C. S. Pramesh
    SUMMARY The right subclavian artery normally arises from the brachiocephalic artery. Anomalies in development may lead to peculiar problems during surgery. We report a patient with esophageal carcinoma who had an aberrant right subclavian artery, posing specific difficulties during a transhiatal esophagectomy, requiring conversion of the procedure into a transthoracic approach. The embryologic basis of this anomaly and the clinical significance are discussed. [source]

    Telomerase activity in small cell esophageal carcinoma

    DISEASES OF THE ESOPHAGUS, Issue 2 2001
    V. Chow
    Small cell carcinoma of the esophagus is a rare and aggressive malignant tumor. Telomerase activation is common in human cancers. There is a lack of data on telomerase activity in esophageal small cell cancers. The present report studied the role of telomerase activity in esophageal small cell carcinoma. The clinicopathologic data of five patients with small cell carcinoma of the esophagus who underwent primary surgical treatment between 1991 and 2000 were studied. Telomeric repeat amplification protocol assays were used to investigate telomerase activity in these tumors. The proliferative activity (MIB-1) and p53 expression of these tumors were also studied using immunohistochemistry and correlated with the telomerase activity. All five small cell carcinomas showed detectable telomerase activity in the primary tumor. Two out of the five morphologically normal esophageal mucosae adjacent to the primary tumor had detectable telomerase activity. There was no correlation between the p53 expression, tumor stage, survival of patients, and the presence of telomerase activity. High MIB-1 expression in esophageal small cell carcinomas was associated with high telomerase activity. Telomerase activation is common in small cell carcinoma of the esophagus. This fact may find application in anti-telomerase treatment for this aggressive tumor. [source]

    COX-2 polymorphisms and the risk for head and neck cancer in white patients

    HEAD & NECK: JOURNAL FOR THE SCIENCES & SPECIALTIES OF THE HEAD AND NECK, Issue 7 2009
    Wilbert H. M. Peters PhD
    Abstract Background. Cyclooxygenase-2 (COX-2) is an enzyme involved in the synthesis of prostaglandins and thromboxanes, which are regulators of processes such as inflammation, cell proliferation, and angiogenesis, all relevant for cancer development. We investigated whether functional genetic polymorphisms in COX-2 may have a risk-modifying effect on head and neck carcinogenesis. Methods. Blood from 431 white patients with oral, pharyngeal, or laryngeal carcinoma and 438 white healthy controls was investigated for the presence of 2 functional promoter region polymorphisms (,1195A,G and ,765G,C) in COX-2. Results. Logistic regression analysis did not show differences in COX-2 genotype distributions between patients and controls. Also no differences were found when stratified according to tumor localization, sex, or tobacco consumption. Conclusion. In contrast to earlier reports on the role of these COX-2 polymorphisms in mediating susceptibility to squamous esophageal carcinoma in a Chinese population, we could not demonstrate a risk-modifying effect in head and neck carcinogenesis in whites. © 2009 Wiley Periodicals, Inc. Head Neck, 2009 [source]

    Frequent decreased expression of candidate tumor suppressor gene, DEC1, and its anchorage-independent growth properties and impact on global gene expression in esophageal carcinoma

    INTERNATIONAL JOURNAL OF CANCER, Issue 3 2008
    Alfred Chi Chung Leung
    Abstract Previous studies showed that expression of the novel candidate tumor suppressor gene, DEC1 (Deleted in Esophageal Cancer 1), is reduced in esophageal carcinoma and suppresses cancer cell growth in vitro and tumor growth in vivo in nude mice. This study shows that DEC1 gene expression was downregulated in 100% of 16 esophageal squamous cell carcinoma (ESCC) cell lines and 52 and 45%, respectively, of esophageal tumor specimens from Hong Kong and a high-risk ESCC region of Henan, China. Using epitope tagging, the DEC1 protein was localized to both the cytoplasm and nucleus of the cell. In 3D Matrigel culture, no significant difference in colony numbers formed was observed for DEC1 stable transfectants, as compared to vector-alone transfectant controls. However, significantly smaller colony sizes were observed for the DEC1 transfectants. In in vitro cell migration, invasion and soft agar assays of DEC1 transfectants, only the soft agar assay showed statistically significant differences in colony numbers with the vector-alone controls, indicating that DEC1 may be involved in anchorage-independent cell growth. In addition, the global gene expression affected by DEC1 in tumor-suppressive stable transfectants was investigated using cDNA oligonucleotide microarray hybridization. Three candidate genes, TFPI-2, GDF15 and DUSP6, were identified through this approach; they are downregulated in tumor segregants of DEC1 stable transfectants, ESCC cell lines and esophageal tumors and have a potential role in tumor growth and progression. These studies show that DEC1 is involved in esophageal cancer development and help elucidate its functional role in tumor development. © 2007 Wiley-Liss, Inc. [source]

    Targeting the epidermal growth factor receptor by erlotinib (TarcevaÔ) for the treatment of esophageal cancer

    INTERNATIONAL JOURNAL OF CANCER, Issue 7 2006
    Andreas P. Sutter
    Abstract Esophageal cancer is the sixth most common cause of cancer-related death worldwide. Because of very poor 5-year survival new therapeutic approaches are mandatory. Erlotinib (TarcevaÔ), an inhibitor of epidermal growth factor receptor tyrosine kinase (EGFR-TK), potently suppresses the growth of various tumors but its effect on esophageal carcinoma, known to express EGFR, remains unexplored. We therefore studied the antineoplastic potency of erlotinib in human esophageal cancer cells. Erlotinib induced growth inhibition of the human esophageal squamous cell carcinoma (ESCC) cell lines Kyse-30, Kyse-70 and Kyse-140, and the esophageal adenocarcinoma cell line OE-33, as well as of primary cell cultures of human esophageal cancers. Combining erlotinib with the EGFR-receptor antibody cetuximab, the insulin-like growth factor receptor tyrosine kinase inhibitor tyrphostin AG1024, or the 3-hydroxy-3-methylglutaryl coenzyme. A reductase (HMG-CoAR) inhibitor fluvastatin resulted in additive or even synergistic antiproliferative effects. Erlotinib induced cell cycle arrest at the G1/S checkpoint. The erlotinib-mediated signaling involved the inactivation of EGFR-TK and ERK1/2, the upregulation of the cyclin-dependent kinase inhibitors p21Waf1/CIP1 and p27Kip1, and the downregulation of the cell cycle promoter cyclin D1. However, erlotinib did not induce immediate cytotoxicity or apoptosis in esophageal cancer cells. The inhibition of EGFR-TK by erlotinib appears to be a promising novel approach for innovative treatment strategies of esophageal cancer, as it powerfully induced growth inhibition and cell cycle arrest in human esophageal cancer cells and enhanced the antineoplastic effects of other targeted agents. © 2005 Wiley-Liss, Inc. [source]

    Randomised comparison of the FerX Ella antireflux stent and the ultraflex stent: Proton pump inhibitor combination for prevention of post-stent reflux in patients with esophageal carcinoma involving the esophago-gastric junction

    JOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY, Issue 5 2008
    Tarun Sabharwal
    Abstract Background and Aim:, Metal stents placed across the gastroesophageal junction in patients with malignant dysphagia frequently present with reflux symptoms. We compared an antireflux stent with a standard open stent used in combination with proton pump inhibitor medication. Methods:, Forty-nine patients with dysphagia due to inoperable carcinoma in the lower third of the esophagus were randomly selected to receive either a antireflux valve stent (FerX-Ella) (n = 22) or a covered standard open stent (Ultraflex), which was combined with proton pump inhibitors such as omeprazole (n = 26). The technical success, the presence of reflux, and complications were recorded. Results:, Reflux was seen in 3/22 patients (13.6%) in the FerX-Ella group and in 2/26 patients (7.7%) in the Ultraflex and proton pump inhibitor combination group (P -value not significant). In both groups, a significant improvement in the dysphagia score was seen and no statistically significant difference was detected between the two groups (P = 0.84). The FerX-Ella stents migrated more frequently (32%) than the Ultraflex stents (23%). This also necessitated surgical intervention more frequently in the FerX-Ella group (2/22, 9.1%) compared to the Ultraflex group (1/26, 3.8%). Conclusion:, The antireflux stent had no demonstrable advantages compared to the combination of standard open stent and proton pump inhibitor medication. [source]

    Mean Corpuscular Volume and ADH1C Genotype in White Patients With Alcohol-Associated Diseases

    ALCOHOLISM, Issue 5 2005
    Leimin Sun
    Background: Alcohol abuse is associated with several gastrointestinal diseases, such as esophageal carcinoma, chronic alcoholic pancreatitis, and liver cirrhosis. Increased mean corpuscular volume (MCV) has been recognized as a biomarker for alcohol abuse and heavy drinkers. Recent studies from Japan revealed that macrocytosis is related to ALDH-2/2 genotype, leading to increased acetaldehyde accumulation. It has also demonstrated that increased MCV values could also be an independent biomarker for esophageal cancer in Asians. Therefore, the aim of the current study was to investigate possible associations of MCV value with polymorphisms of ADH1C in white patients with alcohol-associated esophageal carcinoma, chronic alcoholic pancreatitis, and alcoholic cirrhosis as well as in heavy drinkers without organ damage. Methods: In this study, a total of 510 alcoholic patients were enrolled with esophageal cancer (n= 98), chronic pancreatitis (n= 98), alcoholic liver cirrhosis (n= 151), and alcohol abuse without gastrointestinal disease (n= 163). ADH1C genotyping was performed by PCR-based restriction fragment length polymorphism (PCR-RFLP) analysis from whole blood. The relation between MCV and ADH1C gene polymorphisms (ADH1C*1 and 1C*2) controlled for the amount of drinking, smoking, and age were investigated using both univariate and multivariate analysis. Results: In univariate analysis, higher alcohol consumption was associated with increased MCV. Other variables were not associated with macrocytosis. In multiple linear regression analysis, after adjustment for age and smoking, higher alcohol consumption and female sex were independently associated with higher MCV values. No other variables, including which alcohol-associated disease the patient had, had an independent effect. Adding ADH genotype rendered no independent significant effect on MCV value. Conclusions: In a white population, MCV values were not associated with genotype polymorphisms of ADH1C. In contrast to findings in Asians, macrocytosis does not seem to be an independent biomarker for esophageal cancer. The role of ADH1C polymorphism in increasing MCV and the potential use of MCV as a marker for esophageal carcinoma are still pending. [source]

    Neoadjuvant strategies for the treatment of locally advanced esophageal cancer,

    JOURNAL OF SURGICAL ONCOLOGY, Issue 4 2010
    John R. Hyngstrom MD
    Abstract Patients with locally advanced esophageal carcinoma have consistently poor survival following surgery with associated high systemic and local-regional failure rates. Neoadjuvant therapeutic strategies have been employed in an attempt to improve outcome with variable success. Randomized trials of either neoadjuvant chemotherapy or chemoradiotherapy have shown conflicting results regarding survival and local-regional control. Future efforts should focus on identifying novel agents and targets to improve therapeutic efficacy. J. Surg. Oncol. 2010; 101:299,304. © 2010 Wiley-Liss, Inc. [source]

    Staging of esophageal carcinoma: Length of tumor and number of involved regional lymph nodes.

    JOURNAL OF SURGICAL ONCOLOGY, Issue 5 2006
    Are these independent prognostic factors?
    Abstract 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 ,3 cm (P,<,0.05). Patients with 1,5 LNM had significantly better prognoses than those with more than 5 LNM (Hazard ratio 2.7, 95% CI,=,1.7,4.2) (P,<,0.01). Patients without LNM and more than 15 examined LN showed significantly better prognosis than those with fewer examined LN (Hazard ratio,=,0.3, 95% CI,=,0.1,0.6) (P,<,0.01). Conclusions A revision of the TNM classification for esophageal carcinoma should subdivide the pN1-category according to the number of LNM. J. Surg. Oncol. 2006;94:355,363. © 2006 Wiley-Liss, Inc. [source]

    Expression of L-type amino acid transporter 1 (LAT1) in esophageal carcinoma

    JOURNAL OF SURGICAL ONCOLOGY, Issue 4 2005
    Hideaki Kobayashi MD
    Abstract Background and Objectives It has been reported that amino acid transport systems play an important role in cell proliferation. Their activity is increased in malignant cells compared to benign cells. In this study, we investigated whether L-type amino acid transporter 1 (LAT1) is expressed in human non-cancerous esophageal mucosa and esophageal squamous cell carcinoma. We also examined whether LAT1 expression is correlated with histopathological features. Methods From January 1999 to December 2001, sections of formalin-fixed, paraffin-embedded tissue from 11 cases of early esophageal carcinoma (T1) and 19 cases of advanced esophageal carcinoma (T2, T3) were entered in the study. Histopathologically, all 30 cases were squamous cell carcinoma. Immunohistochemical staining was performed using rabbit anti-LAT1 IgG, with the standard avidin-streptavidin immuno-peroxidase method. Measurement was performed by means of computer-assisted image analysis. The ratio of cells with LAT1 expression in esophageal squamous cell carcinoma and non-cancerous esophageal mucosa was used for analysis in this study. Results Non-cancerous esophageal mucosa expressed LAT1 only in the basal layer of the esophageal wall. Esophageal squamous cell carcinoma expressed LAT1 throughout the tumor. LAT1 expression in esophageal squamous cell carcinoma was significantly higher than that in non-cancerous esophageal mucosa. LAT1 expression in esophageal squamous cell carcinoma increased as the depth of invasion progressed (T1,<,T2 (P,=,0.0477), T2,<,T3 (P,=,0.0415), T1,<,T3 (P,=,0.0044)), and as the tumor size increased. Also, high LAT1 expression was significantly associated with well-differentiated carcinoma. Conclusion These results suggest that LAT1 plays a significant role in cell proliferation, differentiation, and invasion in esophageal squamous cell carcinoma. J. Surg. Oncol. 2005;90:233,238. © 2005 Wiley-Liss, Inc. [source]

    Intra-arterial versus intravenous chemoradiation for advanced head and neck cancer: Results of a randomized phase 3 trial,

    CANCER, Issue 9 2010
    Coen R. N. Rasch MD
    Abstract BACKGROUND: Chemoradiation is the preferred treatment for advanced stage IV head and neck cancer. Higher doses of chemotherapy yielded promising results in vitro and vivo, confirmed by intra-arterial (IA) cisplatin-based chemoradiation in phase 2 studies. METHODS: Two hundred and thirty-nine patients with (functionally) unresectable head and neck cancer were included, from 2000 to 2004, in a multicenter, randomized phase 3 trial, comparing IA and intravenous chemoradiation. Intravenous chemoradiation comprised 3×100 mg/m2 cisplatin infusion on Days 1, 22, 43 combined with 70 Gy in 35 daily fractions. The IA chemoradiation treatment arm comprised 4x150 mg/m2 cisplatin administered in the tumor-feeding artery on Days 1, 8, 15, 22, immediately followed by systemic rescue with sodium thiosulfate with the same radiotherapeutic regimen. RESULTS: Two patients were excluded from analysis because of nontreatment-related death immediately after randomization (n = 1) and esophageal carcinoma (n = 1). The median follow-up was 33 months 1-104 months. Ninety percent of the patients required tube feeding during treatment. Renal toxicity >grade 2 was 9% in the intravenous compared with 1% in the IA treatment arm (P , .0001). There was no difference in locoregional control, disease-free survival (DFS) or overall survival (OS), between the treatment arms. At 3 years, local control, locoregional control, DFS, and OS was .76, .63, .44, .51 in the IA versus .70, .65, .47, .47 in the intravenous treatment arm, respectively. CONCLUSIONS: Cisplatin-based IA chemoradiation was not superior to intravenous chemoradiation for advanced stage IV head and neck cancer regarding locoregional control and survival. Cancer 2010. © 2010 American Cancer Society. [source]

    Health-related quality of life during neoadjuvant treatment and surgery for localized esophageal carcinoma

    CANCER, Issue 9 2005
    Jane M. Blazeby B.Sc., M.D.
    Abstract BACKGROUND Esophagectomy has a negative influence on health-related quality of life (HRQL) during the first postoperative year, but it is not known how chemotherapy or chemoradiotherapy treatment before surgery affects HRQL. The current study examined HRQL during preoperative chemotherapy/chemoradiotherapy treatment and compared postoperative recovery of HRQL in patients undergoing combined treatment with patients undergoing surgery alone. METHODS One hundred three patients completed standardized HRQL measures before and during neoadjuvant treatment and before and after surgery. Mean HRQL scores were calculated and preoperative scores were used to model postoperative ratings using linear regression. RESULTS Deterioration in most aspects of HRQL occurred during preoperative chemotherapy. Patients proceeding to concomitant radiotherapy further deteriorated with specific problems with reflux symptoms and role function (difference between means >15, P < 0.01). After neoadjuvant treatment, but before surgery, HRQL returned to baseline levels. Six weeks after surgery, patients reported marked reductions in physical, role, and social function (difference between means > 30, P < 0.01) and increase in fatigue, nausea and emesis, pain, dyspnea, appetite loss, and coughing (difference between means > 15, P < 0.01). Recovery of HRQL was not hampered by preoperative treatment, and fewer problems with postoperative nausea, emesis, and dysphagia were reported by patients who had undergone neoadjuvant treatment compared with patients who had undergone surgery alone. CONCLUSIONS Preoperative chemotherapy or chemoradiotherapy had a negative impact on HRQL that was restored in patients proceeding to surgery. Recovery of HRQL after esophagectomy was not impaired by neoadjuvant treatment. These results supported the use of neoadjuvant treatment before surgery. Cancer 2005. © 2005 American Cancer Society. [source]

    Prognostic factors in the nonsurgical treatment of esophageal carcinoma with radiotherapy or radiochemotherapy

    CANCER, Issue 8 2005
    The importance of pretreatment hemoglobin levels
    Abstract BACKGROUND The current study was performed to evaluate prognostic factors for overall survival (OS), distant metastasis (DM), and local failure (LF) in patients with Stage II/III esophageal carcinoma. METHODS The following potential prognostic factors were retrospectively investigated in 124 patients treated with radiotherapy (RT) alone or with radiochemotherapy: age, gender, performance status, tumor location, tumor length, histology, histologic grade, T classification, N classification, International Union Against Cancer stage, chemotherapy, RT dose, and pre-RT hemoglobin level. RESULTS Using univariate analysis (Kaplan,Meier method), pre-RT hemoglobin level, RT dose, tumor length, chemotherapy, and performance status were significantly associated with OS. Hemoglobin levels of 12.1,14.0 g/dL were associated with the best OS, followed by , 14.1 g/dL and , 12.0 g/dL. DM was significantly influenced by tumor length, RT dose, N classification, and performance status. LF was significantly influenced by pre-RT hemoglobin level, RT dose, and tumor length. Using multivariate analysis (Cox proportional hazard model), pre-RT hemoglobin maintained significance for OS (P < 0.001) and LF (P < 0.001), RT dose for OS (P = 0.001), DM (P = 0.031), and LF (P < 0.001), tumor length for OS (P = 0.003), DM (P = 0.017), and LF (P = 0.033), and chemotherapy for OS (P = 0.027). N classification was of borderline significance for DM (P = 0.054). Performance status lost significance for OS (P = 0.73) and LF (P = 0.22). CONCLUSIONS The strongest predictors for outcome in Stage II/III esophageal carcinoma were RT dose, tumor length, pre-RT hemoglobin level, and chemotherapy. The pre-RT hemoglobin level was an independent prognostic factor significantly associated with OS and LF. A hemoglobin level of 12.1,14 g/dL resulted in a better prognosis than hemoglobin levels , 14 g/dL and , 12 g/dL. Cancer 2005. © 2005 American Cancer Society. [source]

    The incremental effect of positron emission tomography on diagnostic accuracy in the initial staging of esophageal carcinoma

    CANCER, Issue 1 2005
    Hiroyuki Kato M.D., Ph.D.
    Abstract BACKGROUND The purpose of the current study was to assess whether [18F]fluorodeoxyglucose positron emission tomography (FDG-PET) provides incremental value (e.g., additional information on lymph node involvement or the presence of distant metastases) compared with computed tomography (CT) in patients with esophageal carcinoma. METHODS The authors examined 149 consecutive patients with thoracic esophageal carcinoma. Eighty-one patients underwent radical esophagectomy without pretreatment, 17 received chemoradiotherapy followed by surgery, 3 underwent endoscopic mucosal resection, and the remaining 48 patients received definitive radiotherapy and chemotherapy. The diagnostic accuracy of FDG-PET and CT was evaluated at the time of diagnosis. RESULTS The primary tumor was visualized using FDG-PET in 119 (80%) of 149 patients. Regarding lymph node metastases, FDG-PET had 32% sensitivity, 99% specificity, and 93% accuracy for individual lymph node group evaluation and 55% sensitivity, 90% specificity, and 72% accuracy for lymph node staging evaluation. PET exhibited incremental value over CT with regard to lymph node status in 14 of 98 patients who received surgery: 6 patients with negative CT findings were eventually shown to have lymph node metastases (i.e., they had positive PET findings and a positive reference standard [RS]); 6 patients with positive CT findings were shown not to have lymph node metastases (i.e., they had negative PET findings and a negative RS); and 2 patients were shown to have cervical lymph node metastases in addition to mediastinal or abdominal lymph node metastases. Among the remaining patients, PET showed incremental value over CT with regard to distant organ metastases in six patients. The overall incremental value of PET compared with CT with regard to staging accuracy was 14% (20 of 149 patients). CONCLUSIONS FDG-PET provided incremental value over CT in the initial staging of esophageal carcinoma. At present, combined PET-CT may be the most effective method available for the preoperative staging of esophageal tumors. Cancer 2005. © 2004 American Cancer Society. [source]

    Titration of serum p53 antibodies in 1085 patients with various types of malignant tumors

    CANCER, Issue 3 2003
    A multiinstitutional analysis by the Japan p53 antibody research group
    Abstract BACKGROUND There have been very few large-scale, multiinstitutional studies of surveillance of serum p53 antibodies (S- p53 Abs) in patients with various malignant tumors. METHODS A highly specific, quantitative enzyme-linked immunosorbent assay (ELISA) kit was developed and used to evaluate the efficiency of detecting p53 Abs. A cut-off value was established by analyzing sera from 205 healthy volunteers as reference individuals. Sera from 1085 patients with various types of primary malignant tumors were studied for the presence of S- p53 Abs before treatment. Sera from 34 patients were selected randomly for a competition assay to ensure that antibodies were specific to p53 protein. Carcinoembryonic antigen (CEA) was assessed to compare its positive rate with the positive rate of S- p53 Abs. RESULTS The median value of S- p53 Abs in healthy control individuals was 0.33 U/mL (range, 0.0,4.39 U/mL). Based on reference values that were calculated using parametric determination of the lower 0.95 fraction of the reference distribution in healthy control individuals, the cut-off value was determined as 1.3 U/mL. Two hundred twenty-one of 1085 patients (20.4%) were positive for S- p53 Abs. The highest relevance of S-53 Abs was associated with head and neck carcinoma (32%), followed by esophageal carcinoma (30%), colorectal carcinoma (24%), and carcinoma of the uterus (23%). The positive rate for S- p53 Abs was higher compared with the positive rate for CEA in patients with squamous cell carcinoma. CONCLUSIONS Surveillance of S- p53 Abs is useful in detecting various types of malignant tumors, particular in patients with squamous cell carcinoma. Cancer 2003;97:682,9. © 2003 American Cancer Society. DOI 10.1002/cncr.11092 [source]