Clinical significance of plasma fibrinogen level as a predictive marker for postoperative recurrence of esophageal squamous cell carcinoma in patients receiving neoadjuvant treatment

Among multidisciplinary therapies developed for advanced esophageal cancer, neoadjuvant chemotherapy and chemoradiotherapy have been established as standard treatments. To deliver cautious follow up and intense treatment for high‐risk patients, a simple and instructive biomarker for the postoperative recurrence needs to be identified. Fibrinogen, a common component of hemostasis, has been suggested to not only play an important role in cancer metastasis, but also correlate with tumor recurrence. We aim to clarify the validity of plasma fibrinogen as a marker for predicting the postoperative recurrence of esophageal squamous cell carcinoma patients who received neoadjuvant treatment. We reviewed 72 consecutive patients with esophageal squamous cell carcinoma who received neoadjuvant chemotherapy or chemoradiotherapy, followed by esophagectomy at the Keio University Hospital from 2001 to 2010. Of them, we retrospectively examined 68 patients who underwent plasma fibrinogen examination before and after neoadjuvant treatment and underwent transthoracic radical esophagectomy. We investigated patient characteristics, clinicopathological factors, neoadjuvant treatment effects, postoperative course, and plasma fibrinogen levels. We investigated pretreatment and preoperative (postneoadjuvant treatment) plasma fibrinogen levels, as well as changes in fibrinogen levels before and after neoadjuvant treatment. Patients with preoperative hyperfibrinogenemia (>350 mg/dL) and patients with increased plasma fibrinogen levels during neoadjuvant treatment showed significantly shorter postoperative disease‐free survival (DFS) (P = 0.002 and P = 0.037, respectively). Moreover, we classified these patients into three classes on the basis of their preoperative fibrinogen levels and changes in fibrinogen levels during neoadjuvant treatment. Patients who had both high preoperative plasma fibrinogen and increased fibrinogen levels showed significantly shorter DFS than others. In contrast, patients who had normal preoperative plasma fibrinogen and decreased fibrinogen levels showed significantly longer DFS. Based on this fibrinogen classification, we could differentiate between significantly favorable and poor prognosis patients group. Overall, this classification (hazard ratio = 1.812, P = 0.013) and the response to neoadjuvant treatment (hazard ratio = 0.350, P = 0.007) were found to be significant determining factors for postoperative DFS. With the validity of preoperative plasma fibrinogen levels and changes in fibrinogen levels during neoadjuvant treatment, the plasma fibrinogen level was found to be a possible biomarker for postoperative recurrence in advanced esophageal cancer patients who received neoadjuvant treatment. Moreover, plasma fibrinogen classification could be a simple and valuable predictive marker for postoperative follow up.     

46例食管鳞癌患者术后吻合口复发的高危因素分析

目的 探讨食管鳞癌术后吻合口复发的因素.方法 收集我院2009年9月～ 2013年12月期间在我院行食管癌根治术后出现吻合口复发的患者,应用SPSS 19.0软件对复发情况与可能的影响因素进行κ方单因素分析和Logistic多元回归分析.结果 单因素分析显示,T分期、淋巴结状况（N）分期、切缘距病灶的距离以及肿瘤的分化程度等因素与食管鳞癌的复发有关;多因素研究发现,T分期及切缘距病灶的距离是影响食管癌复发的独立危险因素.结论 食管鳞癌术后患者出现吻合口复发的风险与术后T分期（T）、淋巴结状况（N）、病理分级（G）呈负相关,切缘距病灶越近,发生吻合口复发风险亦越高.     

Prognostic factors in patients with recurrence after complete resection of esophageal squamous cell carcinoma

Background

Recurrence following complete resection of esophageal squamous cell carcinoma (SCC) still remains common. The aim of this study was to investigate the prognostic factors in patients with recurrence after complete resection of esophageal SCC.

Methods

The medical records of 190 patients with recurrent disease after complete resection of esophageal SCC were retrospectively reviewed. Recurrence pattern was classified as loco-regional recurrence and distant metastases. The Kaplan-Meier method was used for the survival analysis. Cox proportional hazards model was used for multivariate analysis.

Results

Mediastinal nodal clearance area was the most common sites of loco-regional recurrence, whereas lung, liver and bone were the most common sites for distant metastases. The median survival after recurrence was 8 months. The 1, 3, 5-year post-recurrence survival rates were 45.9%, 10.6% and 6.4%, respectively. The overall 1, 3, 5-year survival rates were 76.6%, 27.3% and 12.3%, respectively. The independent prognostic factors included time of recurrence (≥12 months vs. <12 months, HR: 3.228, 95% CI: 2.233-4.668), pattern of recurrence (local-regional recurrence vs. distant metastases, HR: 1.690, 95% CI: 1.170-2.439), and treatment of recurrence [no treatment vs. treatment (radiotherapy or surgery or chemotherapy), HR: 0.642, 95% CI: 0.458-0.899].

Conclusions

Our retrospective study showed that time of recurrence, pattern of recurrence and treatment of recurrence were independent prognostic factors in patients with recurrence after complete resection of esophageal SCC.     

Salvage radiotherapy for postoperative loco-regional recurrence of esophageal cancer

The aim of this paper is to evaluate the treatment outcome of radiation therapy (RT) for 16 loco-regionally recurrent esophageal cancer patients. Between 1995 and 2004, patients with loco-regional recurrence of esophageal cancer after curative surgery received RT with or without chemotherapy (CTx) at an average total dose of 56.6 Gy (n = 16, REC group). The site of recurrence was the supraclavicular region in three patients, the mediastinal region in nine patients, and both the supraclavicular and mediastinal regions in four patients. We compared the data with those of patients receiving palliative RT with or without CTx for mediastinal relapse, distant metastasis or malignant pleural effusion (n = 39, META group) and with those of patients receiving postoperative RT with or without CTx in a planned fashion 4-6 weeks after esophagectomy (n = 27, PORT group). The median survival period was 13.8 months in the REC group, 3.5 months in the META group, and 19.1 months in the PORT group. The survival rates at 1 and 2 years were 56% and 19% in the REC group, 6% and 3% in the META group (P = 0.0003), and 70% and 43% in the PORT group (P = 0.1917), respectively. According to univariate analysis, the factor of worse prognosis was not found in the REC group. Complete or partial responses were observed in four (25%) and nine (56%) of the REC group patients, respectively. In the REC group, changes in clinical symptoms, such as dysphagia and recurrent nerve paralysis, could be evaluated in eight patients, and improvement in symptoms was obtained in five (63%) patients. The prognosis of patients who received RT for postoperative loco-regional recurrence of esophageal cancer was significantly better than that of the META group patients and compatible with that of the PORT group patients. Additionally, there is symptomatic relief in a substantial proportion of such patients, and long-term survival is possible in some patients.     

Therapeutic strategy for postoperative liver metastasis from esophageal squamous cell carcinoma; clinical efficacy of and problem with hepatic arterial infusion chemotherapy

BACKGROUND/AIMS: Despite recent advances in diagnosis and treatment, the prognosis for esophageal squamous cell carcinoma is unsatisfactory. Liver recurrence is frequent in postoperative esophageal squamous cell carcinoma patients, and the prognosis for patients with liver metastasis is poor. This report concerns the therapeutic strategy, especially the efficacy of and the problem with hepatic arterial infusion chemotherapy for liver metastasis from esophageal squamous cell carcinoma. METHODOLOGY: We performed a retrospective analysis of 8 patients who underwent hepatic arterial infusion between 1993 and 1998. All patients underwent esophagectomy and reconstruction with stomach roll without preoperative chemotherapy and/or radiotherapy. For 6 patients, preceding systemic chemotherapy was performed before hepatic arterial infusion. RESULTS: The overall response rate of hepatic arterial infusion was 50%, and for the responders, hepatic arterial infusion provided a good quality of life. Hepatic arterial infusion was effective for responders to preceding systemic chemotherapy, but ineffective for non-responders. A complete response was seen in 2 patients, and the liver tumors showed no re-growth after the completion of hepatic arterial infusion. Two patients developed stomach roll ulcers and one experienced the catheter thrombosis, but there were no instances of severe toxicity or complications. CONCLUSIONS: For postoperative liver recurrence of esophageal squamous cell carcinoma, hepatic arterial infusion is the favorable therapy in terms of efficacy and low-grade toxicity, but has a risk of causing severe complications. We consider it suitable that when preceding systemic chemotherapy is performed before hepatic arterial infusion, hepatic arterial infusion is performed in responders to preceding systemic chemotherapy, and that hepatic arterial infusion is continued as long as possible.     

术前放疗与直肠癌术后局部复发的临床观察

目的:探讨直肠癌术前放疗与术后局部复发的关系.方法:直肠癌患者男536例,女226例,年龄21.73(平均48)岁;病理分型:高分化腺癌320例(42.0%),中分化腺癌195例(25.6%),黏液腺癌84例(11.0%),乳头状腺癌40例(5.2%),低分化腺癌50例(6.6%),未分化癌34例(4.5%),腺鳞癌18例(2.4%),印戒细胞癌21例(2.7%).分期:Duckes A期115例,B期399例,C期210例,D期38例.762例行手术(n=589)或手术加术前放疗(n=173)治疗.随访(58-143 mo),了解术前放疗与预后的关系.结果:在762例中,术后局部复发142例(18.6%).其中术前放疗者173例中,术后局部复发19例(11.0%),术前未进行放疗的589例中,局部复发123例(20.9%),两者比较有统计学意义(P<0.05).术前未进行放疗的5 a生存率48.1%,手术前施行放疗的5 a生存率58.4%,两者比较有统计学意义(P<0.05),结论:直肠癌术前放疗可以降低术后局部复发率,提高5 a生存率.     

Clinical usefulness of CYFRA 21-1 for esophageal squamous cell carcinoma in radiation therapy

AIM: The aim of this study was to examine the clinical usefulness of cytokeratin 19 fragments (CYFRA 21-1) compared with squamous cell carcinoma (SCC) antigen in patients with esophageal cancer treated with radiation therapy. METHODS: Fifty-one patients with stage I-IV esophageal cancer were evaluated. CYFRA 21-1 and SCC antigen serum levels were measured at the start and the end of radiation therapy. RESULTS: CYFRA 21-1 (> 3.5 ng/mL) and SCC antigen (> 1.5 ng/mL) before radiation therapy were elevated in 63% and 53% of the patients, respectively. The CYFRA 21-1 levels were significantly correlated with TNM stages, tumor depth and lymph node metastasis (P = 0.0003, P = 0.019 and P = 0.019, respectively), whereas no correlation was observed between SCC antigen and these factors. The values of CYFRA 21-1 in all patients who survived without recurrence were under the cutoff level at the end of treatment, but the values in all patients with locoregional recurrence were above the level. However, there was no significant correlation between SCC antigen level at the end of treatment and any clinical outcome. CONCLUSIONS: The results suggest that the evaluation of CYFRA 21-1 would be useful not only for assessment before radiation therapy but also for monitoring after radiation therapy in the treatment for esophageal cancer.     

Primary radiotherapy with or without chemotherapy in non-metastatic esophageal squamous cell carcinoma: a retrospective study

The purpose of this study was to report the outcome of radio(chemo)therapy in the curative management of esophageal squamous cell carcinoma (ESCC). We retrospectively analyzed 163 patients with T1‐T4, N0‐1, M0 ESCC who were treated between January 1988 and December 2006 at the Technische Universität München. One hundred sixty patients were inoperable due to a poor performance status, comorbidities or locally advanced unresectable disease. External beam radiation therapy (EBRT) was performed with (n= 146) or without (n= 17) systemic chemotherapy. Fifty‐four patients received an additional boost with intraluminal brachytherapy (IBT). Surviving patients were followed for a median of 72 months (range 10–173 months). The estimated overall survival (OS) at 2 and 5 years was 27 ± 4% and 11 ± 3%, respectively. Loco‐regional recurrence at the primary site was observed in 29% of patients (n= 47). The recurrence‐free survival (RFS) at 2 and 5 years was 24 ± 3% and 9 ± 2%, respectively. In multivariate analyses, the ECOG performance status (P= 0.004), 3D conformal (vs conventional) radiotherapy (P= 0.031) and continuous standard fractionation (vs split‐course radiotherapy, P= 0.048) were associated with a better OS. Simultaneous chemotherapy (P= 0.49) or IBT (P= 0.31) had no significant impact on survival. Outcome for patients with ESCC is poor. Despite the very unfavorable patient selection (poor performance status, high rate of comorbidities, and advanced disease), long‐term survival with radio(chemo)therapy was achieved in about 10% of patients. The introduction of modern treatment techniques/modalities (3D conformal planning/ continuous standard fractionation) might be associated with better outcomes.     

Nutrient patterns and risk of esophageal squamous cell carcinoma: a case-control study

Although Iran is a high-risk country for esophageal squamous cell carcinoma (ESCC), the contribution of overall nutrient intakes to this high incidence rate is not yet clear. The aim of this study was to examine the association between nutrient patterns and risk of ESCC in Iran. Forty-seven patients with ESCC and 96 frequency-matched hospital controls underwent private interviews, and dietary habits were collected using a validated food-frequency questionnaire. Factor analysis was conducted and two major nutrient patterns were retained; factor 1 (high in pantothenic acid, vitamin C, potassium, vitamin B(6), magnesium, folate, thiamin, copper, carbohydrate, vitamin K, niacin, α-tocopherol, zinc, total fiber, fluoride, and polyunsaturated fatty acids) and factor 2 (high in saturated fatty acid, biotin, selenium, monounsaturated fatty acids, riboflavin, sodium, fat, cholesterol, calcium, phosphorus, protein, iron, vitamin E, manganese, vitamin D, and vitamin B(12)). Factor 2 was inversely associated with ESCC (OR = 0.06, 95% CI: 0.01-0.28; P = 0.008), whereas no significant association was found for factor 1 (OR = 0.45, 95% CI: 0.11-1.82). The results of the present study suggested a possible role for a nutrient pattern similar to factor 2 in reducing the risk of ESCC.     

Comparison of salvage chemoradiation versus salvage surgery for recurrent esophageal squamous cell carcinoma after definitive radiochemotherapy or radiotherapy alone

A consensus treatment strategy for esophageal squamous cell carcinoma (ESCC) patients who recur after definitive radiochemotherapy/radiotherapy has not been established. This study compared the outcomes in ESCC patients who underwent salvage surgery, salvage chemoradiation (CRT) or best supportive care (BSC) for local recurrence. Ninety‐five patients with clinical stage I to III ESCC who had completely responded to the initial definitive radiochemotherapy or radiotherapy alone and developed local recurrence were enrolled in this study. Fifty‐one of them received salvage esophagectomy, and R0 resection was performed in 41 patients, 36 underwent salvage CRT, and the remaining eight patients received BSC only. The 5‐year overall survival was 4.6% for the 87 patients receiving salvage surgery or CRT, while all patients in the BSC group died within 12.0 months, the difference was statistically significant (P = 0.018). The 1‐, 3‐, 5‐year survival rates in the salvage surgery and salvage CRT groups were 45.1%, 20.0%, 6.9% and 51.7%, 12.2%, 3.1%, respectively, there was no difference of overall survival between the two groups (P = 0.697). Patients also presented with lymph node relapse had inferior survival compared to those with isolated local tumor recurrence after salvage therapy. In the salvage surgery group, infections occurred in eight patients, and three developed anastomotic leakage. In the salvage CRT group, grade 2–4 esophagitis and radiation pneumonitis was observed in 19 and 3 patients, respectively. Seven patients (19.4%) developed esophagotracheal fistula or esophageal perforation. This study of salvage CRT versus salvage surgery for recurrent ESCC after definitive radiochemotherapy or radiotherapy alone did not demonstrate a statistically significant survival difference, but the frequency of complications including esophagotracheal fistula and esophageal perforation following salvage CRT was high.     

Clinicopathologic factors predicting lymph node metastasis in superficial esophageal squamous cell carcinoma

Abstract

Objective. Surgical resection is the treatment of choice for superficial esophageal squamous cell carcinoma (SESCC), but it is associated with high mortality and morbidity rates. Recently, endoscopic resection for SESCC has been indicated for patients with a low risk of lymph node metastasis (LNM). Therefore, to successfully treat SESCC with endoscopic resection, it is very important to identify patients with a low risk for LNM. The objective of this study was to investigate clinicopathologic factors that predict LNM in patients who underwent esophagectomy for SESCC. Methods. The study included 104 patients with SESCC from three university hospitals in Pusan, Korea. Clinicopathologic factors were evaluated to identify independent factors predicting LNM by univariate and multivariate analyses. Results. In univariate analysis, the depth of tumor invasion and lymphovascular invasion had significant influences on LNM (p = 0.001 and p < 0.001, respectively). Gross type, tumor size, and tumor differentiation were not predictive for LNM. In multivariate analysis, the depth of tumor invasion and lymphovascular invasion were signi?cantly associated with LNM in patients with SESCC (OR 9.04, p = 0.049; OR 11.61, p = 0.002, respectively). Conclusions. The depth of tumor invasion and lymphovascular invasion were independent predictors of LNM in patients with SESCC. Therefore, endoscopic resection could be performed in patients with SESCC that is limited to the mucosa, without lymphovascular invasion.     

Changes of serum p53 antibodies and clinical significance of radiotherapy for esophageal squamous cell carcinoma

AIM： To explore the relationship between serum p53 antibodies （p53-Abs） and clinicopathological characteristics and therapeutic effect in patients with esophageal carcinoma （EC）, and to investigate sequential changing regularity of serum pS3-Abs after radiotherapy.
METHODS： The serum pS3-Ab levels were detected in 46 EC patients and 30 healthy adults by enzyme linked immunosorbent assay （ELISA）. The blood samples were collected on the day before radiotherapy and on the administration of an irradiation dose of 20 Gy/10 f/12 d, 40 Gy/20 f/24 d and 60 Gy/30 f/36 d after radiotherapy.
RESULTS： The level and positive rate of serum pS3-Abs in EC patients were significantly higher than those in normal individuals （P 〈 0.05）. Serum anti-p53 antibodies were positive in 18 of 46 EC patients （39.1%）. The positive rate of pS3-Abs in EC was related to histological grade, disease stage and lymph node metastasis （P 〈 0.05）, but it was not significantly related to sex, age and to the size and site of tumor. The level and positive rate of p53-Abs had significant differences between before radiotherapy and after administration of an irradiation dose of 40 Gy/20 f/24 d and 60 Gy/30 f/36 d （P 〈 0.05 orP 〈 0.01）. The positive rate of p53-Abs in EC patients with effect was significantly lower than that in those without effect after radiotherapy （P 〈 0.0001）.
CONCLUSION： Detection of serum p53-Abs is helpful to the diagnosis of esophageal carcinoma. Monitoring for sequential change of serum p53-Abs before and after radiotherapy in patients with esophageal carcinoma is also useful to evaluate the response to the treatment and prognosis of the patients.     

Positive impact of radiation dose on disease free survival and locoregional control in postoperative radiotherapy for squamous cell carcinoma of esophagus

SUMMARY.  The effect of total radiation dose (TRD) on the outcome of patients with postoperative radiotherapy (RT) for squamous cell carcinoma of esophagus was assessed. Sixty-seven patients with esophagectomy, followed by postoperative RT for squamous cell carcinoma of esophagus from June 1984 through February 2001, were retrospectively reviewed. Of these, 13 patients were excluded. No patient had chemotherapy. Patients were classified into two groups based on TRD delivered: TRD of less than 50 Gy (Group A, n  = 16) and at least 50 Gy (Group B, n  = 38). Follow-up duration of all patients ranged from 4 to 140 months (median, 14). Median TRD of Group A and B were 45 Gy (range, 45–48.6) and 54 Gy (range, 50–59.6), respectively. Median overall survival (OS) and disease-free survival (DFS) of all patients were 15 and 10 months, respectively. Although the TRD of 50 Gy or higher was marginally significant for improved OS (hazard ration [HR] 0.559, P  = 0.066), it was statistically significant for improved DFS (HR 0.398, P  = 0.011), and locoregional recurrence-free survival (HR 0.165, P  = 0.001) with multivariate analysis. Three patients in group A and two in group B experienced a complication of grade 3 or higher. Our study suggests a positive impact of TRD of 50 Gy or higher on DFS and locoregional control, with acceptable morbidity in postoperative RT for patients with squamous cell carcinoma of esophagus. According to the present analysis, TRD should be at least 50 Gy in postoperative RT alone setting.     

Salvage radiation therapy and chemoradiation therapy for postoperative locoregional recurrence of esophageal cancer

The purpose of this retrospective study was to assess the efficacy of salvage radiation therapy (RT) or chemoradiation therapy (CRT) for locoregional recurrence (LR) of esophageal cancer after curative surgery. Forty‐two patients who received salvage RT or CRT for LR of esophageal cancer after curative surgery between November 2000 and May 2012 were reviewed. The intended RT regimen was 60 Gy in 30 fractions combined with concurrent platinum‐based chemotherapy. Median follow‐up periods were 17.9 months for all evaluable patients and 28.2 months for patients still alive (19 patients) at analysis time. The 1‐, 2‐, and 3‐year survival rates were 81.2 ± 6.4%, 51.3 ± 8.6%, and 41.1 ± 8.7%, respectively, with a median survival time of 24.3 ± 4.1 months. Out of 41 evaluable patients, 16 patients (39%) were alive beyond 2 years from salvage therapy. However, univariate analyses for overall survival showed no significant prognostic factor. Grade 3 or higher leukocytopenia was observed in 46% of the patients. Salvage RT or CRT for LR after surgery for esophageal cancer was safe and effective. These therapies may offer long‐term survival to some patients. RT or CRT should be considered for LR.     

Expression of EMMPRIN and matriptase in esophageal squamous cell carcinoma: Correlation with clinicopathological parameters

Extracellular matrix metalloproteinase inducer (EMMPRIN) and the type II transmembrane serine protease, matriptase, are expressed in several human cancers and play an important role in tumor progression. The aim of the present study was to investigate the immuno-staining patterns of EMMPRIN and matriptase in patients with esophageal squamous cell carcinomas (SCC) and correlate the percentage tumor staining with tumor differentiation and clinical parameters. EMMPRIN and matriptase immunoreactivity was seen on the cell membrane and in the cytoplasm of tumor cells in all 41 cases of esophageal SCC evaluated. The percentage tumor staining of EMMPRIN was 48 +/- 3% for well differentiated, 73 +/- 3% for moderately differentiated, and 92 +/- 3% for poorly differentiated esophageal SCC. Higher percentage tumor staining with EMMPRIN correlated significantly with poorly differentiated esophageal SCC (P < 0.05). The percentage tumor staining with matriptase correlated significantly with tumor differentiation (52 +/- 3% for well differentiated, 85 +/- 2% for moderately differentiated, and 88 +/- 3% for poorly differentiated esophageal SCC). Additionally, higher percentage tumor staining with matriptase was significantly correlated with the advanced N and M stages (P < 0.05). Our results demonstrate that EMMPRIN and matriptase are over-expressed in esophageal SCC and are correlated with advanced clinicopathological stages. Pharmacological agents targeting EMMPRIN and matriptase expressions may be beneficial in the treatment of esophageal SCC.     

Correlation of ABO blood group with clinicopathologic characteristics of patients with esophageal squamous cell carcinoma

The aim of the current study was to determine the nvolvement of ABO blood group in clinicopathologic features in squamous cell carcinoma (SCC) of the esophagus, that has not previously been studied fully. Two hundred and eighty four consecutive patients with esophageal SCC were enrolled for the study. The relationship between patients' ABO blood group and the clinicopathologic features was analyzed. The proportion of poorly differentiated SCC among patients with blood group O was significantly lower than in those patients with other blood types (P = 0.001). The mean size of the tumors in patients with blood group AB was significantly larger than those in patients with other blood groups. The proportion of tumors associated with venous invasion was significantly higher in patients with blood type A than those of tumors in other blood types (P = 0.007). The TNM stages of tumors in blood group AB were found to be significantly more advanced (P = 0.036) than other groups. The functional significance of ABO blood group distribution might be associated with biological behavior of SCCs. However, it was found not to be a clinical predictor for the prognosis of the patients with esophageal SCC.     

趋化因子受体4在Barrett食管、食管腺癌和食管鳞状细胞癌中的表达及其意义

目的 了解趋化因子受体（CXCR4）在Barrett食管（BE）、食管腺癌和食管鳞状细胞癌中的表达,及其与病理分化程度、临床分期及淋巴结转移之间的关系.方法 应用免疫组织化学SP法对正常食管黏膜56例、BE 80例（其中伴多灶性异型增生22例）、食管腺癌25例和食管鳞状细胞癌组织48例标本中CXCR4的表达进行检测,并用仪器对表达结果进行图像分析,然后进行统计学分析.结果 （1）CXCR4在大部分BE、食管腺癌和食管鳞状细胞癌中呈阳性表达（其阳性率分别为78.8%、68.0%、83.3%）,3组间差异无统计学意义（P＞0.05）,而在正常食管黏膜组中呈阴性或弱阳性表达（阳性率为39.3%）,差异有统计学意义（P＜0.01）;（2）CXCR4在BE、食管腺癌和食管鳞状细胞癌的表达与性别、年龄、病变发生位置均无关（P＞0.05）;（3）CXCR4在BE无异型增生和BE伴多灶性异型增生组织标本中的表达差异无统计学意义（P＞0.05）;（4）CXCR4在食管腺癌高分化较中-低分化者、有淋巴结转移较无淋巴结转移者中的表达均高（P＜0.05）;（5）CXCR4在食管鳞状细胞癌表达水平在肿瘤TNM分期的Ⅲ-Ⅳ级较Ⅰ-Ⅱ级者、有淋巴结转移较无淋巴结转移者中的表达均高（P＜0.05）,高分化较中-低分化则明显更高（P＜0.01）.结论 CXCR4的表达上调可能是食管腺癌和鳞癌的一个普遍特征,与食管病理组织学类型无关,其表达在BE阶段就已上调,并与食管腺癌和鳞癌的分化程度,有无淋巴结转移和TNM分期有一定相关性.CXCR4的表达对BE、食管腺癌和鳞癌的诊断具有指导价值,有可能成为肿瘤治疗的一个新靶点.     

Serum p53 antibody as a predictor of early recurrence in patients with postoperative esophageal squamous cell carcinoma

It is reported that surveillance of serum p53 antibody (Ab) is a useful marker in detecting esophageal squamous cell carcinoma (ESCC). But there is little reported about prognostic significance of serum p53-Ab in postoperative patients with ESCC. The aim of this study is to evaluate the significance of preoperative serum p53-Ab as a marker of early recurrence after curative resection for ESCC. Enzyme-linked immunosorvent assay (ELISA) was used to analyze serum p53-Ab before treatment in 44 patients with ESCC. Carcinoembryonic antigen (CEA) and squamous cell carcinoma antigen (SCC-Ag) were examined by immunoradiometric assay. The patients who were strongly positive and positive in serum p53-Ab were more likely to have early recurrence after curative resection than seronegative patients. There were no significant correlations between CEA, SCC-Ag positivity and early recurrence. We found that serum p53-Ab was useful to predict a risk of early recurrence after curative surgical resection for ESCC.     

Association between esophageal squamous cell carcinoma and human papillomavirus detected by Hybrid Capture II assay

From July 1999 to July 2000, 40 patients from the Surgical Oncology and Gastroenterology Departments of Irmandade da Santa Casa de Misericórdia de Porto Alegre were enrolled in a prospective study in order to find the frequency of human papillomavirus DNA (HPV-DNA) in esophageal squamous cell carcinoma. They were compared to 10 normal individuals (controls). Digene Inc. (Digene Corporation, Gaithersburg MD, USA) Hybrid Capture II assay, a chemoluminescent method, was used in both groups. The samples were collected from the tumor group by endoscopic biopsy in 20 cases, and by surgical specimens in the other 20 cases; the control group all underwent endoscopic biopsies. The cut-off point in the analytical assay for HPV-DNA was 1.0 pg/mL. Digene Corp. Hybrid Capture II assay tests HPV-DNA and differentiates high and low-risk for malignization virus groups. Gender, age, location of the tumor in esophagus and degree of differentiation on histology were also analyzed. There was one positive case (1.14 pg/mL), a 2.5% frequency of low-risk HPV-DNA type in the esophageal squamous cell carcinoma group (CI 95%: 0.00-7.34%). This group of patients consisted of 30 male and 10 female individuals, similar to the distribution seen in large series of such patients from the Brazilian population. The mean age was 63 years. Endoscopic samples of 10 patients who underwent endoscopic biopsy procedure for aleatory reasons, with normal looking esophageal mucosa, were tested to detect HPV-DNA, as controls. There was one positive case (1.17 pg/mL) of high-risk HPV-DNA type, resulting in a 10% positive rate. HPV-DNA is rarely found in esophageal squamous cell carcinomas: we found a 2.5% frequency, with confidence interval of 0-7.34%; and this is in the same range of controls (10% frequency, with CI: 9.1-10.9%). Both patients had a viral load quite near the 1.0 pg/mL cut-off point.