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Purpose: Evaluating the status of disease progression is critical for planning a therapeutic strategy for esophageal cancer. In this regard, F-18 fluorodeoxyglucose-labeled positron emission tomography (PET) is one of the most useful diagnostic modalities. However, there is room to improve its diagnostic performance, such as distinguishing lymph nodal metastases from false positives. In this study, we examined the diagnostic accuracy of fluorodeoxyglucose PET accompanied by computed tomography imaging (PET/CT) to detect regional lymph nodal metastasis from esophageal squamous cell carcinoma (ESCC)., Methods: A total of 102 patients diagnosed as ESCC were subjected to this study. These patients had a preoperative PET/CT examination to evaluate the existence of metastasis. The values of maximum standardized uptake value (SUVmax) in primary tumors and in metastasized lymph nodes were measured to analyze their relationship with various clinicopathologic characteristics including the status of tumor cell proliferation, which was assessed by immunohistochemistry for Ki-67., Results: The SUVmax of the primary tumor was positively correlated with tumor size and vessel invasion, and was positively related with the SUVmax of lymph nodal metastasis, especially in cases of poorly differentiated ESCC. The SUVmax of metastasized lymph nodes was higher in larger-sized metastasized lymph nodes, whereas the Ki-labeling index of lymph nodal metastasis was positively related with the SUVmax per unit area (SUVmax/mm). The diagnostic accuracy of PET/CT (87.3%) was higher than that of conventional CT scans (78.4%)., Conclusions: The improved diagnostic accuracy of PET/CT can be explained by its ability to detect actively progressive metastasis at an early phase regardless of size.

The clinical efficacy and safety of hyperfractionated radiotherapy with concurrent chemotherapy were studied retrospectively in patients with primary advanced esophageal cancer. The subjects were 31 patients who were treated with hyperfractionated radiotherapy and concurrent chemotherapy in our institution between 1990 and 2001. The chemoradiotherapy consisted of cisplatin 70-80 mg/m2 on day one, and continuous infusion of 5-fluorouracil 700-800 mg/m2/24 hours on days 1 to 3, with concurrent hyperfractionated radiotherapy (57.6-72 Gy). Complete remission (CR) was observed in 17 cases, and partial response in 13 cases (response rate: 96. 7%). Three-year survival rate and 5-year survival rate were 35.5% and 26.3%, respectively. Grade 3/4 hematological toxicities included leukocytes in 7 patients (22.6%), hemoglobin in 6 patients (19.4%), and platelets in 4 patients (12.9%). Grade 3 dysphagia-esophageal related to radiation was observed in 3 patients (9.7%). Late toxicities occurred with the following incidences: hypothyroidism in 2 patients, benign esophageal strictures in 2 patients, pericardial effusion in 8 patients, and pleural effusion in 8 patients. The results suggest that combined chemotherapy and hyperfractionated radiotherapy is an effective and well-tolerated regimen.

Background and Objectives: Although some investigators recently suggested that MMP-9 may play a critical role in invasion and metastasis, along with MMP-2, in esophageal carcinoma, there has been no direct evidence that MMPs play a critical role in the actual invasion of esophageal carcinoma cells. Here, we investigated the role of MMPs in the in vitro invasion of esophageal carcinoma cell lines (TE-series)., Methods: Our methods included in vitro invasion assay, gelatin zymography, and enzyme-linked immunosorbent assay (ELISA)., Results: Four cell lines (but not TE-5) secreted MMP-2 and MMP-9 in the culture medium. Using a quantitative in vitro invasion assay, we found a significant (P = 0.002) correlation between the extent of in vitro invasion and the amount of MMP-9, but not of MMP-2, secreted into the conditioned medium in the four cell lines. In these cell lines, R-94138, a specific MMP-9 inhibitor, inhibited in vitro invasion in a dose-dependent manner. Although TE-5 did not secrete MMP-2 or MMP-9, the cells showed a strong in vitro invasion., Conclusions: Our data suggest that most of the esophageal carcinoma cell lines use MMP-9 for in vitro invasion, but others may use proteinase(s) other than MMP-9., (Copyright 2002 Wiley-Liss, Inc.)

Purpose: In some patients who already have advanced esophageal cancer at the time of presentation, symptoms like the inability to eat, and complications such as bronchoesophageal fistula are so debilitating that palliative resection may be beneficial. However, resection of the esophagus is associated with significant risk, and whether this operation should be performed for palliation remains controversial. Because few reports have been published on this subject, we retrospectively analyzed 24 patients with esophageal cancer who underwent palliative resection., Methods: Esophageal resection was performed with palliative intent in 12 patients and with curative intent in another 12 who were left with residual cancer., Results: There was no operative death. All of the ten patients who had been unable to eat preoperatively were able to eat after the operation, and four patients with a life-threatening bronchoesophageal fistula were free of symptoms after the operation. Two patients died in hospital during the postoperative chemotherapy but the other 22 were discharged. The mean survival period was 264 days., Conclusions: With improved postoperative care, the risk of palliative esophageal resection is no longer considered unacceptable.

Background and Objectives: Telomerase has been suggested as being necessary for continued cell growth and progression of cancer. Esophageal cancer and matched normal esophageal tissue from 54 patients were analyzed for telomerase activity, human telomerase reverse transcriptase (hTERT) mRNA expression, and their correlation with clinicopathological factors., Methods: Telomeric repeat amplification protocol was used for detection of telomerase activity and real time quantitative RT-PCR was used for hTERT mRNA. An esophageal carcinoma cell line was used to study the effect of chemotherapeutic agent on telomerase., Results: Telomerase activity was detectable in 79.6% of the tumor and 59.3% of the normal esophageal tissue. The level of telomerase activity in the tumor was significantly higher than that in the normal tissue. A significantly higher telomerase activity was observed in tumors with extensive blood vessel invasion. A significantly lower telomerase activity was observed in tumors that showed good response to preoperative chemotherapy than those with poor response. TE-9 cells exposed to 5-FU showed a diminished telomerase activity preceded by a time-dependent decrease in the mRNA expression of hTERT., Conclusions: Telomerase activity was high in esophageal cancer tissue and showed positive correlation with blood vessel invasion. Chemotherapeutic agents may down-regulate telomerase activity., (Copyright 2002 Wiley-Liss, Inc.)

Survivin, a new member of the inhibitor-of-apoptosis (IAP) family, has been reported to be expressed in many cancers but not in differentiated normal tissue. Its expression in esophageal cancer, however, has not been reported. We investigated 51 esophageal cancers and their adjacent normal epithelial tissues for mRNA expression of survivin by RT-PCR. The survivin expression in esophageal cancer tissue was significantly higher than that in normal esophageal tissue (0.211 +/- 0.226 vs. 0.057 +/- 0.135, p < 0.0001). pN4 tumors had significantly higher survivin expression than the pN0-3 tumors (p = 0.0093). Fourteen patients with advanced esophageal cancer had received chemotherapy prior to surgery. The survivin expression in the cancer tissue in patients who achieved a partial response (PR) was significantly lower than that in patients with no change (NC) and in patients with progressive disease (PD; 0.099 +/- 0.134 vs. 0.320 +/- 0.222, p = 0.0434). The median survival for patients with high survivin expression (9.0 months) was less than that for patients with low survivin group expression (30.0 months, p = 0.0023). Survivin expression was one of the significant predictors of survival on univariate analysis (hazard ratio 2.471; 95% confidence interval 1.104-5.533). The results suggest that survivin expression may provide prognostic information in patients with esophageal cancer., (Copyright 2001 Wiley-Liss, Inc.)

Background: Carcinomas of the cervicothoracic esophagus frequently invade the trachea and complete removal of the tumor often requires mediastinal tracheostomy. Traditionally, this surgical management was associated with high morbidity and mortality. Several types of myoctaneous flaps have been used for mediastinal tracheostomy to reduce the complication. We present our experience with a new technique for construction of mediastinal tracheotomy after total laryngoesophagectomy and reconstruction with the stomach., Methods: The anterior chest wall was amply resected and the distal end of the trachea was placed low between the superior vena cava and aortic arch. We mobilized the entire omentum with the stomach and brought them up to the neck through the posterior mediastinum. The omentum was put around the trachea, main arteries, and the anastomosis., Results: Seven mediastinal tracheostomies were performed using this method. There was no hospital death. Complications included respiratory failure (2 patients) and pyothorax (1 patient). Anastomotic leakage and inominate artery rupture were not experienced. Postoperative survival was disease dependent. All patients were discharged with satisfactory oral food intake, good airway condition, and excellent cosmetic appearance., Conclusions: We suggest the use of the omentum as a simple and reliable technique in constructing mediastinal tracheostomy following total laryngoesophagectomy for cervicothoracic esophageal cancer.

Patients with small cell carcinoma of the esophagus have a poor prognosis and have generally been treated by chemotherapy. However, all reported cases were at advanced stages. We need to establish an adequate treatment for patients with small cell carcinoma of the esophagus with invasion limited to the submucosal layer. In this paper, five cases of small cell carcinomas, which accounted for 2.8% of 180 surgically treated esophageal carcinomas, were reviewed for pathological findings, treatment, and outcome. Among three patients who had a small cell carcinoma of the esophagus with invasion limited to the submucosal layer, two patients survived for 7 and 9 years after surgery with no evidence of the disease. One of them was treated using surgery alone. Consequently, surgery may be considered as a possible choice of treatment for small cell carcinoma of the esophagus with invasion limited to the submucosa.