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The purpose of this study was to analyze loss of p16 expression and its relationship to hypermethylation, clinicopathological parameters and prognosis in patients with esophageal squamous cell carcinoma (ESCC). Tissue samples from 60 ESCC were subjected to histological analysis. Immunohistochemical staining for p16 expression was performed. DNA was extracted from these primary esophageal tumors and from sera from another 38 ESCC patients. The DNA was modified with bisulfite and analyzed for p16 promoter methylation by methylation-specific polymerase chain reaction. Twelve out of the 60 tumors (20%) were methylated at the p16 promoter and 48 tumors (80%) were unmethylated. There were no significant correlations between the methylation of the p16 promoter and clinicopathological parameters. Immunohistochemical staining revealed that 41 of the 60 tumors (68.3%) were p16-negative and 19 tumors (31.7%) were p16-positive. The correlation between negative p16 immunohistochemical staining and methylation was statistically significant ( P = 0.0084). No instances of p16 methylation and p16 positive immunostaining were found. There was a close correlation between loss of p16 expression and poorer prognosis in ESCC ( P = 0.0517 in overall survival, P = 0.0478 in disease-free survival). The p16 gene promoter hypermethylation was detected in the serum of two of 38 (5.2%) patients with ESCC. This indicates that p16 promoter methylation suppresses p16 expression and that the loss of expression has a close relationship with poor prognosis in patients with ESCC. The present results may lead to the development of new therapeutic strategies, such as p16 INK4A gene therapy, to treat patients with ESCC. [ABSTRACT FROM AUTHOR]

Aggressive surgery including extensive lymph node dissection is considered necessary to improve the long-term survival of patients with esophageal carcinoma. While three-field lymph node dissection is widely performed for patients with thoracic esophageal carcinoma, cervical lymph node metastasis is uncommon. In order to reduce surgical stress, we have developed a two-step three-field lymph node dissection procedure for thoracic esophageal carcinoma. In the first-step operation, total thoracic esophagectomy through a right thoracotomy is performed. Mediastinal and abdominal lymph node dissection is performed synchronously. When recurrent nerve lymph node metastasis is pathologically positive, cervical lymph node dissection is performed about 3 weeks after the first operation (second step). Of 343 patients with carcinoma of the esophagus surgically treated in our department between 1990 and 2001, 146 underwent the operation described above. Three-field dissection was performed in 68 patients (group A), while two-field dissection was performed in 78 patients (group B). In the 68 group A patients, cervical lymph node metastasis was positive in 15 patients (22%). There was no marked difference in the onset of major complications between the two groups. The 5-year survival rate was 58% for group A and 61% for group B, not a statistically significant difference. In 78 of the 146 patients, it was possible to avoid cervical lymph node dissection without negatively affecting therapeutic outcomes. Two-step three-field lymph node dissection can reduce surgical stress of patients with good clinical outcome. [ABSTRACT FROM AUTHOR]

Pyrimidine nucleoside phosphorylase (PyNPase) converts 5′-deoxy-5-fluorouridine to 5′-fluorouracil, which exerts an anticancer effect before being catabolized by dihydropyrimidine dehydrogenase (DPD). Recently, PyNPase has been shown to be identical to a potent angiogenic factor, platelet-derived endothelial cell growth factor. We analyzed the concentration of PyNPase and DPD in 33 patients with esophageal squamous cell carcinoma in fresh–frozen samples by enzyme-linked immunosorbent assay. In addition, we evaluated the clinical significance and prognostic value of PyNPase expression in esophageal carcinoma. The PyNPase concentration of tumor tissue was statistically higher than that of normal tissue of the esophagus (248 ± 146 U/mg protein vs 73 ± 63 U/mg protein, P = 0.0001), whereas DPD showed no difference (90 ± 62 U/mg protein vs 88 ± 62 U/mg protein, P = 0.825). The ratio of PyNPase to DPD of tumor tissue was statistically higher than that of normal tissue of the esophagus (3.3 vs 0.95, P = 0.0001). There were no significant differences between the group with high tumor to normal tissue ratios of PyNPase concentration and the low-ratio group in terms of the tumor length, depth, lymph node metastasis, lymph vessel invasion, vascular invasion, stage and survival. In conclusion, 5′-deoxy-5-fluorouridine may be effective on esophageal carcinoma and PyNPase concentration in esophageal carcinoma may not be a useful prognostic marker for patients with esophageal squamous cell carcinoma. [ABSTRACT FROM AUTHOR]

Small cell carcinoma arising in the esophagus is a relatively rare disease. In the more common small cell carcinoma of the lung, the diagnostic significance of several new markers has been recently reported. This study used immunohistochemical techniques in addition to clinicopathological analysis, in order to clarify the utility of newer markers as biological parameters or as diagnostic tools. Six patients with small cell carcinoma of the esophagus were clinicopathologically analyzed. Immunohistochemical staining was performed using primary antibodies for bombesin, CD56 and CD57 in addition to conventional endocrine markers chromogranin A, neuron specific enolase and synaptophysin. All patients died within 2 years of surgery due to cancer recurrence, whether or not they had received adjuvant therapy. Pathological stages ranged from IIa to IVb and lymph node metastasis was observed in five cases. Of the six cases, four showed a positive reaction for bombesin and five were positive for CD57. In contrast, no cases revealed a positive reaction for CD56. The one case to survive 24 months after surgery was not shown to express bombesin, CD56 or CD57. Small cell carcinoma of the esophagus demonstrated an unfavorable prognosis. The study suggested that in this disease, bombesin and CD57 (but not CD56) were useful as biological markers, predicting clinical outcome rather than having diagnostic significance. [ABSTRACT FROM AUTHOR]

SUMMARY Apoptosis is one of the critical biological factors that correlate with the biological behavior of malignant tumors including cancer progression and clinical outcome. The present study was performed to clarify the clinical implications of BAG-1, a bcl-2 binding protein in esophageal squamous cell carcinoma (ESCC). Seventy-one cases with ESCC were investigated. Immunohistochemical study of BAG-1 was performed on resected specimens. The expression pattern of BAG-1 in nuclei and/or cytoplasm was analyzed and correlated with TNM classification, vessel invasion, survival period after surgery. BAG-1 expression in the nuclei was related to the depth of tumor invasion (P = 0.0381) but not to any other clinicopathologic parameters. The cytoplasmic staining pattern of BAG-1 exhibited no correlation with clinicopathologic parameters. Univariate analysis (P < 0.05), but not multivariate analysis, revealed significantly poor prognosis for ESCC cases exhibiting positive nucleic staining for BAG-1. Our data suggests that BAG-1 expression in the nuclei of ESCC plays an important role in tumor development and may be useful for predicting the prognosis after surgery. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

SUMMARY Reconstruction of cervical esophagus and hypopharynx following cervical esophagectomy and laryngopharyngectomy is generally performed using jejunal autograft interposition. However, this method has some disadvantages and is not suitable for optimal swallowing function. In our institution, free transverse colonic graft has been successfully applied for reconstructive purposes in 12 cases since 1986. The present report describes a case of upper esophageal web accompanying superficial squamous cell carcinoma and details the operative techniques utilized. [ABSTRACT FROM AUTHOR]

Recently, neoadjuvant chemotherapy combined with radiation (NAT) has been used in the active treatment of progressive esophageal cancer (T4). However, many patients are resistant to supplemental therapy, and it is necessary to to be aware that side-effects may occur. Accordingly, to minimize adverse reactions and cost, it is important to determine the indications for NAT. We investigated 34 patients with T4 esophageal squamous cell carcinoma and examined the relation between the effects of NAT and immunohistochemical or additional clinicopathologic factors. There was no relation between clinicopathologic factors and immunohistochemical findings (p53 or hsp27 expression), and no clinicopathologic factors showed a relation to a supplemental therapeutic effect. In addition, there was no correlation between p53 staining and therapeutic effects (P=0.734). In contrast, there was a correlation (P=0.0058) between hsp27 staining and therapeutic effect. In conclusion, the usefulness of hsp27 immunostaining in predicting the therapeutic effect of NAT was confirmed in T4 esophageal squamous cell carcinoma. [ABSTRACT FROM AUTHOR]

SUMMARY We present the case of a 26-year-old woman who underwent a successful laparoscopic resection of an esophageal duplication cyst without any other congenital abnormalities. Although computed tomography (CT) scan and endoscopic ultrasonography (EUS) both assisted in determining the correct preoperative diagnosis, the definitive diagnosis was made following pathological examination of the resected lesion. [ABSTRACT FROM AUTHOR]