Search

This study assessed the clinical value of CYFRA 21-1 in comparison with squamous cell carcinoma antigen (SCC-Ag), carcinoembryonic antigen (CEA), and carbohydrate antigen 19-9 (CA19-9) in patients with esophageal squamous cell carcinoma. In 112 primary cancer patients, the diagnostic sensitivity of CYFRA 21-1 (33.9%) was superior to SCC-Ag (28.6%), CEA (12.5%), and CA19-9 (6.3%). Levels of CYFRA 21-1 were closely correlated with TNM stage and were below the cutoff value in all 21 patients with stage I disease. All 38 patients with a CYFRA 21-1 level over the cutoff value among the 80 patients who underwent esophagectomy had lymph node metastases (pNl). A correlation was found between CYFRA 21-1 levels and clinical response in serial measurements of 21 patients who received chemotherapy or chemo radiotherapy. Our findings suggest that CYFRA 21-1 is not useful for diagnosis, but that it is valuable for monitoring the efficacy of therapy., (© 1998 International Society for Diseases of the Esophagus/Harcourt Brace & Co. Ltd.)

It is difficult to perform radical surgery for esophageal cancer with multiple lymph node metastases. Therefore, effective neoadjuvant adjuvant treatment is necessary to achieve successful radical resection. The use of neoadjuvant chemotherapy of docetaxel, cisplatin (CDOP) and 5-fluorouracil (5-FU) (DCF) in an advanced case is reported. The patient (a 67-year-old female) was diagnosed with esophageal cancer, T3, N4, M0, stage IVa with a large number of lymph node metastases in the mediastinum and in the abdominal cavity. Neoadjuvant DCF chemotherapy was initiated in August 2006. Adverse events were mild. A complete response of the lymph node metastases in the abdominal cavity and a partial response of the esophageal lesion were achieved. The surgical procedure included a right thoracolaparotomy followed by a subtotal excision of the esophagus and two-field lymph node dissection. The cancer was diagnosed to be moderately differentiated squamous cell cancer, pT2, pN4(3c) and pstage IVa. The histological efficacy of the chemotherapy was determined to be grade 1a. Two additional courses of DCF therapy were administered followed by postoperative adjuvant chemotherapy.

A 70-year-old male was admitted to our hospital because of advanced esophageal squamous cell carcinoma and early gastric adenocarcinoma. A esophagectomy and partial gastrectomy with three-field lymph node dissection (neck, mediastinum and abdomen) was performed. Both tumors had lymph node metastases. In addition, three mediastinal lymph nodes (two subcarinal lymph nodes and a middle thoracic paraesophageal lymph node) were involved with adenocarcinoma. To elucidate whether they were metastases from the gastric cancer, an immunohistochemical analysis was performed. The cancer cells in these lymph nodes were positive for cytokeratin (CK) 7 and negative for CK 20, thus suggesting metastasis from a nondigestive organ. Interestingly, they were positive for thyroid transcription factor 1 (TTF-1), indicating metastasis from a lung cancer. Since the preoperative computed tomographic scan showed no evidence of lung cancer, a diagnosis of metastases from an occult lung cancer was finally recorded. Ten months after surgery, the patient was alive without a recurrence or the appearance of a lung cancer.

A case of collision carcinoma (squamous cell carcinoma and Barrett's adenocarcinoma) in the residual cervical esophagus of a 68-year-old woman at 27 years after subtotal esophagectomy for thoracic esophageal carcinoma is reported. The patient initially noticed cervical dysphagia in 2002, but did not seek treatment. In April 2004, the patient was referred to our department by a local physician with the diagnosis of carcinoma of the cervical esophagus. In September 2004, the patient underwent resection of the cervical esophagus and partial resection of the gastric tube combined with cervical lymph node dissection under a diagnosis of double cancer (i.e., metachronous cervical esophageal carcinoma and carcinoma of the gastric tube). Esophagogastric continuity was restored by transplantation of a free jejunal graft with vascular anastomosis. Pathological examination showed squamous cell carcinoma on the esophageal side of the esophagogastric anastomosis and columnar epithelium with a tongue-shaped extension across the anastomotic line that included Barrett's epithelium, as well as adenocarcinoma, on the gastric tube side. The squamous cell carcinoma and adenocarcinoma were contiguous, but there was a distinct border between them and no morphological transition. Immunohistochemical staining showed positivity for p53 in the squamous carcinoma cells, while it was negative in the adenocarcinoma cells. In contrast, HER2 (c-erb-2) was strongly positive in the adenocarcinoma cells, but negative in the squamous carcinoma. Based on these findings, it was concluded that two separate carcinomas had arisen at different sites and grown independently until they collided and merged to form a collision carcinoma.

Background/aims: To evaluate the impact of surgery on survival after chemoradiotherapy, we analyzed the long-term outcome of patients with advanced esophageal cancer., Methodology: Data on 92 consecutive patients with T3 or T4 esophageal cancer who were initially treated by chemoradiotherapy were reviewed retrospectively. Of 82 patients who completed the planned schedule, 35 patients underwent esophagectomy (CRT+E Group) and 47 patients received definitive chemoradiotherapy (CRT Group)., Results: A response to chemoradiotherapy was obtained in 71% of all 92 patients. The 1- and 3-year survival rates in the patients with T3M0 were 87 and 44 percent respectively, while these in the patients with T4 and/or M1(Lymph) disease were 47 and 20 percent. Although there was no difference in overall survival between the CRT+E Group and the CRT Group, the survival of responders in the CRT+E Group was significantly higher than that of those in the CRT Group (P=0.0448). The locoregional recurrence rate of responders in the CRT Group was higher than that in the CRT+E Group. Multivariate analysis showed that the independent prognostic factors were response, M(Lymph), and esophagectomy., Conclusions: Although this study was retrospective and nonrandomized, esophagectomy after chemoradiotherapy might improve the survival of responders for locoregional control.

Objective: In order to assess the usefulness of esophagectomy through mini-thoracotomy/laparotomy as a minimally invasive surgical procedure for esophageal cancer, we compared the results to those of conventional right thoracotomy/laparotomy., Methods: From 1998 to 2002, 40 patients with thoracic esophageal cancer were prospectively assigned to two groups. Twenty patients underwent esophagectomy through mini-thoracotomy/laparotomy (M-group), while the other 20 had conventional thoracotomy/laparotomy (C-group). Surgical complications, the duration of the systemic inflammatory response syndrome (SIRS), postoperative pain, cytokine responses, and respiratory function were compared between the two groups., Results: There was no difference of morbidity between the M- and C-groups after surgery. There were also no differences between the two groups with respect to the operating time, bleeding, and number of dissected lymph nodes. The duration of SIRS was shorter in the M-group than in the C-group (p = 0.055). Use of morphine was lower in the M-group than in the C-group with patient-controlled anesthesia (p = 0.002). The interleukin-6 level of the M-group was lower than that of the C-group at 3, 6 hours, and 3 days after the operation. Recovery of vital capacity by the M-group was better than by the C-group after the operation. Postoperative hospital stay of the M-group was significantly shorter than that of the C-group (p = 0.014). Long-term survival was not different in the two groups., Conclusion: Mini-thoracotomy/laparotomy reduces invasiveness and pain compared with conventional thoracotomy/laparotomy for esophagectomy without causing any differences of morbidity or long-term survival.

Background: In Japan, concurrent chemoradiotherapy is the standard treatment for unresectable esophageal cancer. The optimal combination of chemotherapeutic agents and radiotherapy dose remains controversial. The present study consists of a phase II trial of a cisplatin (CDDP)/5-fluorouracil (5-FU) infusion with concurrent radiotherapy in patients with unresectable, advanced esophageal cancer., Methods: Between March 13, 1996, and April 28, 1998, 60 patients with advanced squamous cell carcinoma of the thoracic esophagus having either T4 tumor or distant lymph node metastasis (M1 Lym) were enrolled in this study. CDDP 70 mg/m(2) was administered on days 1 and 29, and 5-FU 700 mg/m(2)/day was administered on days 1-4 and 29-32. Fractionated radiotherapy was performed on days 1-21 and 29-49; a total dose of 60 Gy was delivered at the rate of 2 Gy per fraction., Results: The overall response rate of all the 60 registered patients was 68.3% (41/60), and the complete response rate was 15% (9/60). The median survival time was 305.5 days, and the 2-year survival rate was 31.5%. One toxicity-related death occurred. The major form of toxicity exceeding grade 2 was found to be myelosuppression; grade 4 toxicity was observed in five patients., Conclusion: Based on the overall response rate, the results obtained from the present trial do not appear to be promising. However, it is currently suitable for the treatment of patients with unresectable, advanced esophageal cancer because of certain clinical advantages, a higher CR rate and a lower incidence of fistula formation. A phase II/III trial will be started in order to compare low-dose continual CDDP/5-FU infusion and concurrent radiotherapy with the results obtained in this study.

Background: Although local recurrence of advanced esophageal cancer is frequent after definitive chemoradiotherapy (CRT), the clinical benefit of salvage esophagectomy has not been elucidated., Methods: We reviewed 27 patients with squamous-cell cancer who underwent esophagectomy after definitive CRT (> or = 50 Gy) (salvage group) and 28 patients who underwent planned esophagectomy after neoadjuvant CRT (30 to 45 Gy) (neoadjuvant group)., Results: The preoperative albumin level and vital capacity were significantly lower in the salvage group than in the neoadjuvant group. Two patients (7.4%) from the salvage group who underwent extended esophagectomy with three-field lymphadenectomy died of postoperative complications, but no deaths occurred after less-invasive surgery. There was no difference of overall postoperative survival between the salvage and neoadjuvant groups., Conclusions: The outcome of salvage esophagectomy after definitive CRT was similar to that of planned esophagectomy after neoadjuvant CRT. Less-invasive procedures might be better for salvage esophagectomy because of the high operative risk., (Copyright 2004 Excerpta Medica, Inc.)

A 32-year-old woman was admitted to our hospital with dysphagia. An upper gastrointestinal series revealed Borrmann type 2 esophageal cancer in the lower thoracic esophagus. Because direct invasion of the thoracic aorta was suspected, FAP therapy (CDDP, 5-FU and ADM) was given as neoadjuvant chemotherapy. After completion of two courses, her dysphagia resolved and the tumor shrank by over 90%, so radical surgery was performed. No lesions were found when the resected specimen was examined macroscopically. The only histological change was hyperplasia of collagen fibers in the submucosa, lamina propria and adventitia of the esophagus. No cancer cells and no metastases to the lymph nodes were observed. Because the tumor had completely disappeared, the histological effect of chemotherapy was classified as grade 3, i.e., pathological complete response (PCR). The response to FAP therapy was excellent and no serious adverse events occurred. Therefore, this is one of the treatments that should be actively applied in patients who have advanced esophageal cancer with suspected lymph node metastasis and invasion of other organs.

Detection of micrometastasis to the bone marrow can predict widespread disease and a poor prognosis of cancer patients. The purpose of this study was to evaluate the clinical significance of detecting micrometastasis in the bone marrow of esophageal cancer patients. Bone marrow and peripheral blood samples were obtained from 52 squamous esophageal cancer patients at the time of surgery. These samples were enriched by immunomagnetic separation and immunostained with an anti-cytokeratin antibody. Expression of vascular endothelial growth factor (VEGF) and cyclin D1 was examined in the primary tumors. Cytokeratin-positive cancer cells were observed in the bone marrow of 13 (25%) out of 52 patients. Among them, three patients also had cancer cells in the peripheral blood. The presence of bone marrow micrometastasis was correlated with lymph node metastasis (pN) but not associated with depth of tumors (pT). Detection of bone marrow micrometastasis was significantly correlated with VEGF expression of the primary tumors. Cumulative survival of patients with bone marrow micrometastasis was significantly lower than that of patients without it (p=0.0008). Hematogenous recurrence was more frequent in patients with bone marrow micrometastasis than in those without it (p=0.0004). Three patients who had local or dissemination recurrence did not have bone marrow micrometastasis. Detection of cancer cells in the bone marrow might be an indicator of early hematogenous metastasis in esophageal cancer patients. Intensive postoperative chemotherapy seems to be indicated for these patients.

Chemoradiotherapy is a multimodal therapy routinely used as a primary treatment for advanced esophageal cancer. However, it is beneficial only to patients who respond. To identify pretreatment markers predicting response and survival, we examined the expression of cell cycle regulatory molecules, p53, p21(Waf1/Cip1) cyclin D1, and CDC25B, in biopsy specimens from 76 patients with stage III and stage IV squamous cell carcinoma. Overexpression of p53, p21, cyclin D1 and CDC25B was observed in 58%, 30%, 28%, and 32% of patients, respectively. The expression of p21 correlated significantly with response to chemoradiotherapy (P = 0.0001). Survival of patients with p21-expressing tumors was better than that of patients with p21-negative tumors (P = 0.013). Expression of other genes was not significantly correlated with treatment response and survival. In patients with p53-negative tumors, survival of those patients with p21-positive tumors was significantly higher than that of those with p21-negative tumors (P = 0.0452), but no significant difference was found in patients with p53-positive tumors. Multivariate analysis revealed that p21 expression was an independent variable among pretreatment parameters in predicting survival. These results suggest that p21 expression is potentially useful for predicting the response to chemoradiotherapy and survival of patients with advanced esophageal squamous cell cancer.

Purpose: We performed a multicenter randomized controlled trial to determine whether postoperative adjuvant chemotherapy improves outcome in patients with esophageal squamous cell carcinoma undergoing radical surgery., Patients and Methods: Patients undergoing transthoracic esophagectomy with lymphadenectomy between July 1992 and January 1997 at 17 institutions were randomly assigned to receive surgery alone or surgery plus chemotherapy including two courses of cisplatin (80 mg/m2 of body-surface area x 1 day) and fluorouracil (800 mg/m2 x 5 days) within 2 months after surgery. Adaptive stratification factors were institution and lymph node status (pN0 versus pN1). The primary end point was disease-free survival., Results: Of the 242 patients, 122 were assigned to surgery alone, and 120 to surgery plus chemotherapy. In the surgery plus chemotherapy group, 91 patients (75%) received both full courses of chemotherapy; grade 3 or 4 hematologic or nonhematologic toxicities were limited. The 5-year disease-free survival rate was 45% with surgery alone, and 55% with surgery plus chemotherapy (one-sided log-rank, P =.037). The 5-year overall survival rate was 52% and 61%, respectively (P =.13). Risk reduction by postoperative chemotherapy was remarkable in the subgroup with lymph node metastasis., Conclusion: Postoperative adjuvant chemotherapy with cisplatin and fluorouracil is better able to prevent relapse in patients with esophageal cancer than surgery alone.

Background/aims: Cyclin D1 expression is one of the important biologic factors and its close association with p16/INK4 and retinoblastoma protein expression has been proven in patients with esophageal squamous cell carcinoma, however, the clinical implication of these associations is still unknown. The objective of this study is to clarify its clinical significance., Methodology: We studied p16, cyclin D1, and pRB expression using immunohistochemistry in the resected specimens of 156 patients who underwent curative esophagectomy., Results: Alteration of p16 expression, positive cyclin D1 expression and loss of pRB expression were demonstrated in 108 (69%) patients, 47 (30%) patients, and 48 (31%) patients, respectively. An inverse correlation was found between p16 expression and pRB expression (P < 0.0001). Of 47 cyclin D1-positive tumors, 39 (83%) tumor exhibited alteration of p16 and 43 (92%) tumors were positive for pRB. Based on p16, cyclin D1, and pRB expression, 138 (88%) patients were divided into the following three groups: p16-/cyclin D1+/pRB+ (n = 44), p16+/cyclin D1-/pRB- (n = 38), p16-/cyclin D1-/pRB+ (n = 56). The three groups were the most influential prognostic factors in a Cox's proportional regression model. The p16-/cyclin D1+/pRB+ group had frequent hematogenous recurrence, while the other groups had frequent lymph node recurrence., Conclusions: Assessment of p16, cyclin D1, and pRB expression may be helpful for determining postoperative therapeutic strategies in patients with esophageal squamous cell carcinoma.

Background and Study Aims: A standard treatment for esophageal squamous cell carcinoma (SCC) with submucosal invasion is considered to be radical resection at present. In this study, we evaluated the efficacy of multimodality treatments with endoscopic mucosal resection (EMR) of esophageal SCC with submucosal invasion., Method: Eighteen cases of SCC with submucosal invasion were treated with EMR. Lymphatic invasion was found in 11 cases (67%), and there were no cases of blood vessel invasion. EMR was performed prior to any other treatment. Chemotherapy and/or radiotherapy were added if indicated by the histopathological features., Results: There were no cases of local recurrence. Lymph-node recurrence was detected in 1 case treated with EMR alone. There were no cases of cancer death. The overall survival rate was 83% in all patients., Conclusions: Multimodality treatments with EMR were effective in treating esophageal SCC with submucosal invasion.

We conducted a pilot study of nedaplatin + 5-fluorouracil (5-FU) combined with radiotherapy for 29 patients with primary advanced (stage IV) esophageal cancer. A complete remission (CR) was obtained in 4 (14%) and a partial response in 13 patients (response rate: 59%). The median survival time and one-year survival rate were 238 days and 34.5%, respectively. Of the 29 patients, 24 (83%) completed the treatment schedule and toxicity of stomatitis and the like was infrequent. In conclusion, these results suggest that the efficacy of nedaplatin + 5-FU combined with radiotherapy might not differ from that of cisplatin + 5-FU combined with radiotherapy. Clearly, the usefulness of this combined therapy needs to be assessed in multicenter phase III trials.

We reviewed case reports of malignant melanoma in the alimentary tract and discussed the diagnosis and treatment. Cases of malignant melanoma in the alimentary tract have mostly originated from the esophagus and an anorectal lesion. Metastatic tumors occurred mainly in the stomach and the small intestine. Although resection with lymph node dissection was performed, the prognosis of these patients was worse than that of patients with carcinoma. Malignant melanoma of the alimentary tract might be more aggressive than that of the skin. A combined modality treatment including progressive chemotherapy and biotherapy is expected to improve the prognosis of these patients.

Lymph node metastasis (LMN) in esophageal cancer occurs from the superficial cancer and spreads wildly from the neck to the abdomen. Hence precise determination of LMN is essential when adequate treatments are employed. There are several reports about ultrasonic features of malignant lymph nodes (LNs), and in summary, reports of endoscopic ultrasonography (EUS) findings of malignant LNs showed they were more than 5-10 mm in diameter, with a distinct border, hypoechoic internal echo and round shape. Sensitivity, specificity and accuracies for the diagnosis of malignant LNs by EUS were 49-99%, 33-99% and 71-96%. The rates widely varied, because the accuracy of EUS's ability to determine malignancy were based on the evaluation of various echo features of LNs, and were dependent on the judgement of subjective observers. Therefore histological analysis is necessary for adequate treatments. Endoscopic ultrasonography guided fine-needle aspiration cytology (EUS-FNA) has been performed for the diagnosis of malignant LNs since 10 years. Results of those reports were sensitivity 81-97%, specificity 83-100% and accuracy 83-97%. EUS-FNA staging was better than EUS staging. Also clinically obvious complications by EUS-FNA have not been reported. Therefore published evidence showed that EUS-FNA is safe and useful for confirmation of malignant LNs.

Background and Objectives: Lymph node micrometastasis is frequently detected in resected specimens of esophageal squamous cell carcinoma (ESCC). The goal of this study was to evaluate the clinical implication of micrometastasis in patients with lymph node-negative (pN0) disease., Methods: We examined the presence of micrometastasis in 2,511 lymph nodes from 53 patients with pN0 disease who underwent curative esophagectomy. All lymph nodes and the primary tumors were immunostained using an anticytokeratin antibody cocktail (AE1/AE3)., Results: Micrometastasis was detected in 18 lymph nodes (0.72%) from 14 patients (26.4%). Detection of micrometastasis was not associated with the depth of invasion or the differentiation or lymphatic invasion. Lymph nodes containing micrometastases were widely distributed, but the most frequently involved nodes were located along the lesser curvature of the stomach. Four patients with micrometastasis (29%) and the only two patients without micrometastasis (5%) had recurrence as lymph node metastases (P = 0.036). There were no significant differences in recurrence-free survival and disease-specific survival between patients with micrometastasis and patients without micrometastasis., Conclusions: These results show that micrometastasis might increase the risk of lymph node recurrence, but does not influence the survival of patients with pN0 ESCC., (© 2002 Wiley-Liss, Inc.)

In our institute, radical esophagectomy through mini-thoracolaparotomy has been performed as a less-invasive surgery for esophageal cancer since 1996. We describe the indications for and operative procedures of mini-thoracolaparotomy. Next we report the preliminary results of a prospective randomized trial that compared mini-thoracolaparotomy with conventional thoracolaparotomy in 30 patients without neoadjuvant therapy. There were no differences between the two groups in operative time, bleeding volume, and number of dissected lymph nodes. Thoracolaparotomy was effective in decreasing the quantity of morphinerequired in the ICU and shortening hospitalization after surgery. Thoracolaparotomy was effective in preventing a decrease in and early recovery of postoperative vital capacity. In clinical data on radical esophagectomy performed through a right thoracotomy and reconstruction with a stomach tube from 1996 to 2000, the 5-year survival rate of 63 patients in the thoracolaparotomy group (67.6%) did not differ from that of 124 patients in the conventional surgery group (49.9%).

Adenocarcinoma of the esophagogastric junction is recognized as a distinct clinical entity; however, the choice of surgical approaches is controversial. To analyze the results of surgery among patients with adenocarcinoma of the esophagus (type I) and the cardia (type II) based on Siewert's classification in Japan, surgical procedures, histopathologic characteristics, and outcome were re-evaluated according to the TNM classification in 1263 patients with adenocarcinoma of the esophagus (type I) and the cardia (type II) through a questionnaire sent to the members of the Japanese Society of Esophageal Diseases. One hundred and thirty-four (10.6%) patients had type I tumors and 1129 (89.4%) patients had type II tumors. There were significant differences in sex distribution and associated intestinal metaplasia in the esophagus between patients with type I and type II tumors. Although different surgical approaches were performed, the overall 5-year survival rate was 53% without any difference between the two groups. The significant prognostic factors in general linear models were R category, pN category, and differentiation, but not pT category. There was no difference in survival between patients with stage IIB and III disease. The survival rate of the patients who underwent a transhiatal approach was similar to that of those undergoing a transthoracic approach. The results suggest that Siewert's classification (type I and type II) is useful in planning treatment strategy for adenocarcinoma of the esophagogastric junction. Lymph node metastasis was the most important prognostic factor, and staging based on the number of lymph node metastases or the extent of lymph node metastasis is necessary.

Background: Surgery for advanced esophageal carcinoma has its limits as regards aggressiveness and therapeutic effect, therefore effective multimodality treatment is required to obtain better survival. The objective of this study was to evaluate whether daily continuous infusion of CDDP could achieve a higher clinical response rate with less toxicity than its drip infusion in the previous phase II study that we had conducted., Methods: Patients with primary extensive or relapsed esophageal carcinoma after esophagectomy, which had distant organ metastasis and histologically proven SCC, were eligible for this study. A dose of 20 mg/m(2) of cisplatin and 800 mg/m(2) of 5-fluorouracil was given by continuous infusion for 24 h on days 1-5. This treatment was repeated every 4 weeks for up to four cycles. A total of 36 men and six women with a median age of 64 (range 39-75) years were registered and 36 patients were eligible., Results: The overall response rate of the registered patients was 33.3% (12/36) and the median response duration was 175 days. Median survival time was 201.5 days and the 1-year survival rate was 27.8%. Change from bolus to continuous infusion of cisplatin affected neither the type nor the degree of toxicity., Conclusion: Daily continuous infusion of cisplatin was not associated with higher response or lower toxicity than those seen with the high-dose bolus or multibolus treatment regimens. We conclude that this regimen in this setting is not worthy of further phase III trials. JEOG is now evaluating other drug combination regimens.

Background: Recent developments in detection of micrometastasis have revealed a considerable incidence of systemic disease in patients who would previously have been diagnosed as having solid tumours only. The purpose of this study was to investigate the prevalence and clinical significance of circulating carcinoma cells in patients with esophageal squamous cell carcinoma (ESCC)., Materials and Methods: Peripheral blood samples from 47 primary ESCC patients were enriched by immunomagnetic separation (IMS) using Ber-EP4-conjugated beads (Dynabeads anti-epithelial cell) and immunostained with an anti-cytokeratin (anti-CK) antibody. We assayed samples from 12 patients to compare the detection of CK-reactive cells using IMS with the detection of CK 19 mRNA using a reverse transcriptase-polymerase chain reaction (RT-PCR) method., Results: CK-reactive cells were observed in 18 out of 47 patients (38%). The detection rate was closely correlated with the stage of disease (TNM stage) (p = 0.0017). In 33 patients who underwent esophagectomy, 4 out of 7 patients (57%) positive for CK cells and only 2 out of 26 patients (7.7%) negative suffered from recurrence in the distant lymph nodes or lungs (p = 0.0108). When IMS and RT-PCR were compared, all 3 samples that were CK-positive by IMS had CK 19 mRNA detected by RT-PCR. However, the other 4 samples with CK 19 mRNA by RT-PCR were negative for CK cells by IMS. Of 7 patients positive for CK-reactive cells before chemotherapy or chemoradiotherapy, 4 patients negative after treatment survived but 3 patients who remained positive died within 6 months., Conclusion: Immunocytochemical detection of circulating carcinoma cells by IMS may be a specific method for the diagnosis of systemic disease and for monitoring treatment response.

Background: Exact clinical staging before treatment of esophageal cancer has become increasingly important in the evaluation and comparison of the results of different treatment modalities, including surgery, chemotherapy, and radiotherapy., Methods: The accuracy of preoperative tumor staging by using an esophagography, esophagoscopy, percutaneous and endoscopic ultrasonography, and computed tomography was assessed in 224 patients with resectable esophageal cancer. The results of tumor staging by these tests were compared prospectively with the pathologic stage of the esophagectomy specimens with respect to the T and N categories defined by the International Union Against Cancer TNM classification., Results: For the T category, the overall accuracy was 80%. For the N category, overall accuracy was 72%, with a sensitivity of 78%, a specificity of 60%, and a positive predictive value of 78%. Overall, the accuracy of stage grouping was 56%., Conclusions: Either the T or N categories can be predicted reliably by clinical staging techniques. However, the preoperative stage grouping might not be valid in resectable, localized esophageal cancer.

Postoperative complications were investigated in 72 patients who received neoadjuvant therapy with esophagectomy. Preoperative chemotherapy consisted of 5-fluorouracil (700 mg/m2/day, on days 1 to 5), cisplatinum (70 mg/m2/day, on day 1) and leucovorin (20 mg/m2/day, on days 1 to 5). Preoperative chemoradiotherapy consisted of cisplatinum combined chemotherapy and radiotherapy (total dosage of 30-70 Gy). The incidence of postoperative pneumonia (16%) and anastomotic leakage (24%) in the preoperative chemotherapy group was slightly higher than that in the control group (n = 506), and mortality (6.0%) after esophagectomy in the preoperative chemotherapy group was higher than that (2.4%) of the control group. Postoperative morbidity and mortality were observed more frequently in patients who received two cycles of the chemotherapy than those receiving only one cycle. Postoperative complications occurred more frequently in patients suffering high grade toxicities due to the preoperative chemotherapy. The highest preoperative serum creatinine value correlated to that of postoperative period (r = 0.6494). The use of the preoperative chemoradiotherapy with a total exposure dosage of 60 Gy or more significantly increased the postoperative pneumonia rate (67%; p < 0.05) compared to the group receiving 40 Gy or less. The mortality rate (33%) also increased. The second cycle of the preoperative chemotherapy should be cancelled if patients suffer high grade toxicities during or after the first cycle, and the total exposure dosage of the preoperative chemoradiotherapy should be limited to 40 Gy or less.

This study assessed the clinical value of CYFRA 21-1 in comparison with squamous cell carcinoma antigen (SCC-Ag), carcinoembryonic antigen (CEA), and carbohydrate antigen 19-9 (CA19-9) in patients with esophageal squamous cell carcinoma. In 112 primary cancer patients, the diagnostic sensitivity of CYFRA 21-1 (33.9%) was superior to SCC-Ag (28.6%), CEA (12.5%), and CA19-9 (6.3%). Levels of CYFRA 21-1 were closely correlated with TNM stage and wee below the cutoff value in all 21 patients with stage I disease. All 38 patients with a CYFRA 21-1 level over the cutoff value among the 80 patients who underwent esophagectomy had lymph node metastases (pN1). A correlation was found between CYFRA 21-1 levels and clinical response in serial measurements of 21 patients who received chemotherapy or chemo radiotherapy. Our findings suggest that CYFRA 21-1 is not useful for diagnosis, but that it is valuable for monitoring the efficacy of therapy.

Objective: To determine whether postoperative adjuvant chemotherapy confers a survival benefit on patients with esophageal squamous cell carcinoma undergoing radical surgery, we undertook a cooperative, prospective randomized controlled trial., Methods: A total of 205 patients underwent transthoracic esophagectomy with lymphadenectomy at eleven institutions between December 1988 and July 1991. These patients were prospectively randomized into two groups (100 patients underwent surgery alone and 105 patients had additional two courses of combination chemotherapy with cisplatin (70 mg/m2) and vindesine (3 mg/m2). The two groups did not differ with respect to sex, age, location of tumor, and distributions of pT, pN, pM, or p stage., Results: The 5-year survival was 44.9% in the surgery alone group and 48.1% in the surgery plus chemotherapy group. The relative risk was estimated to be 0.89 (95% confidence interval, 0.61 to 1.31) in the surgery plus chemotherapy group compared with the surgery alone group. No significant differences in survival were detected between the two groups, even with lymph node stratification., Conclusion: Postoperative adjuvant chemotherapy with cisplatin and vindesine has no additive effect on survival in patients with esophageal cancer compared with surgery alone.

Forty-four patients with advanced esophageal squamous cell carcinoma were treated with biochemical modulated combination chemotherapy and surgery. Treatment consisted of cisplatinum (70 mg/m2/day 1, day 22), 5-fluorouracil (5-FU; 700 mg/m2/day, days 1-5, 22-26), and leucovorin (20 mg/m2/day, days 1-5, 22-26) with nutritional support, and surgery (days 42-70, mean day 56). Surgery consisted of subtotal esophagectomy with extended lymphadenectomy. Postoperative adjuvant chemotherapy or additional irradiation to the mediastinum was restricted to patient with residual tumors. Clinical response rate was 63.6% in primary tumor, 52.6% in intramural metastasis, 100% in intraepithelial spread, and 30.9% for metastatic lymph nodes. There was a slight disagreement between the result of evaluation of histological and clinical effect. The incidence of postoperative complications was 25%, and the mortality rate was 2.3%. Overall 1-, 2-, 3-, and 4-year survival rates of the patients were 57%, 37.9%, 28.5%, and 28.5%, respectively. The median survival time was 14.7 months. Responders survived longer than nonresponders. The histological responders survived longer than clinical responders. The 4-year survival rate of patients without residual tumor after treatment was 75% in the superficial cases, 51% in the locoregional cases, and 50% in the widespread cases.

In patients with esophageal cancer, combined chemotherapy is usually given as a part of multimodality treatment and therefore undesirable toxicity should be diminished. Recently, the most standard protocol against esophageal cancer has been Cisplatin/5-FU combination, of which the response rate is 40-60%. We showed the development of chemotherapy and chemoradiotherapy using Cisplatin/5-FU for esophageal cancer. In recent Japanese protocols, continuous infusion of Cisplatin for several days or bolus injection of low-dose Cisplatin are supposed to be mainstream. The supra additive effect of leucovorin to Cisplatin +5-FU considering biochemical modulation is confirmed, and Cisplatin/5-FU/adriamycin protocol study is ongoing.

A phase II study of chemoradiotherapy for advanced squamous cell carcinoma of the thoracic esophagus was carried out cooperatively by nine Japanese institutions. Forty-five patients with thoracic advanced squamous cell carcinoma, who had T4 tumor or distant lymph node metastasis (M1(LYM)), were enrolled in the study for treatment with cisplatin (70 mg/m2) on days 1 and 36, and 5-fluorouracil infusion (700 mg/m2) on days 1-4 and 36-39 sandwiched around external beam irradiation (60 Gy over 6 weeks). Of the 45 evaluable patients, 37 (84.1%) completed the treatment. The overall response rate was 64.4%, and the complete response rate 8.9%. The median duration of response was 125.0 days for patients who achieved complete and partial response. The 50% median survival time was 215 days. There was one toxicity-related death due to radiation pneumonitis. The major form of toxicity exceeding grade 2 was myelosuppression and anorexia, but grade 4 toxicity was also observed (2 pulmonary, 1 severe hypoxemia, 1 severe cardiac failure and 1 mental disturbance). The results showed that this form of chemoradiotherapy had a satisfactory effect and might be useful for treatment of inoperable advanced esophageal cancer.

A total of 83 specimens of surgically resected tumours from 78 patients with oesophageal cancer were assayed for drug sensitivity using an adhesive tumour cell culture system (LifeTrac CSA assay). Seventyone of 83 specimens had a sufficient number of cells to permit growth in culture and 57 of 71 (80%) were evaluable for drug response. Cells (3 x 10(3) ml-1 well-1) were cultured for 14 days and exposed to drugs on days 3-8. Growing cells were confirmed as cancer cells by immunohistochemical staining. IC90 values against several anti-cancer drugs were determined and population distributions of IC90 for each drug served as the basis for judging sensitivity. The 10th percentiles of IC90 (microgram ml-1) for CDDP, 5-FU, DOX, CPM, MTX, VP16, IFOS, VDS, BLM and CDDP + 5-FU were 0.3, 0.16, 0.005, 0.9, 0.006, 0.09, 0.8, 0.006, 0.04 and 0.15 + 0.09 respectively. The population distribution of IC90 against each drug showed a specific pattern that was very similar among histopathological gradings and stages of the disease. This system appeared to be a clinically applicable drug sensitivity test for human oesophageal cancer.

Background: In esophageal cancer it is important to distinguish between mucosal cancer and cancer invading the submucosa to determine the feasibility of endoscopic mucosal resection., Methods: Endoscopic ultrasonography using a small probe 2.6 mm in diameter at 15 or 20 MHz frequency was employed to determine the depth of superficial esophageal cancer invasion in 54 patients. Group 1 consisted of 17 cases treated by endoscopic mucosal resection on the basis of ultrasonographic findings. Group II included 37 patients treated by conventional surgery. The resected specimens were compared with ultrasonographic findings., Results: The normal esophageal wall was depicted as having nine layers, the fourth hypoechoic layer (m4) on the high frequency image was confirmed to be the muscularis mucosa. Based on the ultrasound findings, cancer limited to the lamina propria was accurately determined in 84%. In the endoscopic mucosal resection cases, 15 were mucosal cancer whereas 2 cases had microscopic invasion of the submucosa., Conclusions: High-frequency ultrasound probes were sufficiently accurate for the determination of the depths of invasion of early esophageal cancer to guide the application of endoscopic resection of mucosal cancer.

The points of the postoperative care in radical operation of esophageal cancer are followings. 1) Postoperative nutritional management: In the reconstruction using gastric tube, we make Witzel's gastrostomy in antrum of regardless of the reconstructive routes and transfer to enteral tube-feeding to assist the oral food-taking amount. These management is not only attributing to assist early return to working but also effective to prevent the loss of postoperative physical strength in older patients. 2) Postoperative adjuvant therapy: The esophageal cancer is the diseases that react chemo- and radio-therapy, so most of advanced cases were treated with adjuvant therapy. Nowadays, it is essential for patients to explain the real diagnosis, treatment regimen, then to agree to the informed concent. After informed, the tender mental consult during treatment and outpatient service is required for mental burden. 3) Postoperative follow-up: The recognition of postoperative QOL, early detection of recurrence are mostly emphasized during 2 years after operation. The occurrence of secondary cancer (gastric cancer, cervico-pharyngeal cancer, colorectal cancer etc.) are seen in even 5-10 years after operation. Then the long-term periodical examination and life care are needed.

We compared the clinical and pathological effects of preoperative combination chemotherapy using CDDP, 5-FU, and response rate for the primary lesion, an 81.8% response rate for intramural metastasis, 100.0% for intraepitherial spread, and a low response rate of 40.7% for lymph node metastasis. Pathological examination showed a 55.2% response rate for the primary lesion. There were seven cases in which the clinical assessment indicated that treatment was effective and pathological examination showed that it was ineffective, and three cases in which pathological examination showed a better response than clinical assessment. Cases showing a better clinical response included in which necrotic cancer lesion had disappeared due to absorption by the time of pathological examination, those with tumor regrowth after preoperative evaluation, those evaluated as showing a poor response due to residual cancer at the margin. Cases showing a better pathological response included those having remaining necrotic tissues and those having myoma beneath tumor. For intramural metastatic lesions, the pathological response rate was 42.9%, being lower than the clinical response rate. Metastasis to 209 lymph nodes showed a 23.0% response rate, with the abdominal nodes showing a poor response in comparison with those of the cervix and mediastinum. In 26 patients receiving preoperative radiotherapy, there was a significantly higher frequency of such changes as fibrous scar tissue, foreign body giant cells, vacuolation of tumor cells, and hyaloid degeneration of the lesion in comparison with the group receiving chemotherapy. Another difference was that the radiotherapy group showed a higher response of tumors with venous and lymphatic involvement.(ABSTRACT TRUNCATED AT 250 WORDS)

We examined the p53 protein and human papilloma virus (HPV) by immunohistochemistry and DNA ploidy by cytofluorometry in paraffin-embedded esophageal carcinoma tissue specimens. Sixty-one patients with superficial esophageal carcinoma were operated on between 1983 and 1991 without any prior treatment. Immunostaining of the anti-p53 protein antibody (CM1) was positive in 32 carcinomas (52%). Patients with p53-positive tumors had a poorer outcome than those with p53-negative tumors (P < 0.05). In addition, patients with p53-positive tumors did not have any characteristic site of relapse. Only 5 of the 61 patients (8.2%) had HPV-positive tumors. One of these 5 carcinomas expressed both p53 protein and HPV. Three patients with HPV-positive tumors which had invaded the submucosal layer died of relapse. A determination of DNA ploidy revealed 30 patients with aneuploid tumors, 13 with polyploid tumors and 18 with diploid tumors. The outcome of the patients with aneuploid tumors was worse than that of the patients with diploid tumor (P < 0.05). p53 protein expression was not associated with DNA ploidy; however, the 16 patients who had both p53-positive and aneuploid tumors had a worse prognosis than patients with p53-negative and aneuploid tumors (P < 0.01). These findings suggest that p53 protein expression in conjunction with DNA ploidy may be a useful indicator in evaluating the prognosis of patients with superficial esophageal carcinoma.

Purpose: The results of definitive radiotherapy for superficial esophageal cancer is presented., Methods and Materials: Twenty-one patients with superficial squamous cell carcinoma of the esophagus were treated by definitive radiotherapy with megavoltage x-rays in Tokyo Women's Medical College from 1975 to December 1990. Eight patients refused surgery and 13 patients were considered to be unsuitable for surgery due to advanced age or morbid conditions such as severe pulmonary dysfunction, myocardial infarction, liver cirrhosis, and other cancer. Radiotherapy was performed using 1.8-2.2 Gy fraction dose, 5 times a week and with a total dose of 50-76 Gy/5-7 weeks (median; 70 Gy). Three patients received intraluminal radiotherapy in addition. Combined chemotherapy was performed in four cases, and three cases received it before radiotherapy and one case after radiotherapy., Results: Overall survival rate was 40.8%, and the cause-specific 5-year survival rate was 61.7%. The 5-year survival rate of the group with morbid conditions was 17.5%, but that of the group without morbid conditions was 60.6%. Seven patients developed recurrence (primary site: 3, lymph nodes: 3, lung: 1) and one patient revealed multicentric cancer of the hypopharynx with wide submucosal spread of the esophagus at 28 months after radiotherapy. No patient developed severe side effect due to radiotherapy., Conclusion: Definitive radiotherapy with or without chemotherapy can be applied as an alternative therapy to surgery for superficial esophageal cancer, even for the operable patients under good general condition.

In a multi-center case-control study, we evaluated the risk of esophageal cancer in the Japanese population. All patients and controls were inpatients in the surgical departments of seven hospitals nationwide. Patients eligible for the study were those newly diagnosed as having primary esophageal cancer. One control per case was selected from among patients admitted to the same hospital, and 141 male pairs were analyzed using logistic regression analysis. The results showed dose-response relation between the risk of esophageal cancer and both the quantity (g/week) and frequency (times/week) of alcohol drinking (P value for trend = 0.0001). Although a statistically significant risk increase was shown among moderate to heavy smokers (15 < or = cigarette/day < 25) (odds ratio, 4.35:95% confidence interval, 1.81-10.49), the dose-response for cigarette smoking was unclear (P value for trend = 0.07). No combined effect of alcohol drinking and cigarette smoking was found. A frequent intake of fruit was associated with a decreased risk (P value for trend = 0.02). After adjustment for alcohol consumption, cigarette smoking and fruit intake were found not to be associated with the risk, whereas a preference for high-temperature food and drink showed a statistically significant positive association (P value for trend = 0.02). Drinkers who consumed shochu most frequently showed a three-fold increased risk over that for beer consumers, although the association disappeared after adjusting for the amount of alcohol consumed. The present results confirm alcohol intake and a preference for high-temperature food to be associated with an increased risk of esophageal cancer and show the amount of alcohol consumed, rather than the type of alcoholic beverage, to be the main risk determinant.

This paper reviews clinical trials for esophageal carcinoma, mainly from the results of the JEOG (Japanese Esophageal Oncology Group) study. Preoperative radiotherapy was not conducive to survival of esophageal cancer patients. On the third JEOG trial, postoperative chemotherapy of CDDP+VDS was equivalent to survival as 50Gy of postoperative irradiation. And on the further fourth trial, survival was also equivalent between the two groups treated with surgery alone or postoperative chemotherapy of CDDP+VDS. This fact reveals the in effectiveness of these therapies. The response rate from JEOG phase II study of CDDP and 5-FU was 35.9%, and RCT of surgery alone versus surgery + postoperative chemotherapy with CDDP+5-FU was ongoing as the fifth JEOG trial. Chemo-radiotherapy seemed to be very effective for esophageal cancer patients, and it may provide a complete cure for them in the future.

From 1990 to 1991, 40 patients with squamous cell carcinoma of the thoracic oesophagus were admitted to our institutions and chemotherapy (oil Bleomycin p.o. and CDDP d.i.v.) either combined with or without hyperthermia was performed, in a prospective randomized trial carried out to investigate the effects of hyperthermia. The two groups (group A, consisting of 20 patients given chemotherapy alone; and group B, made up of 20 given chemotherapy with hyperthermia) were comparable with regard to various prognostic factors. Following the above treatment regimens, an oesophagectomy was done in 16 and 17 patients from groups A and B, respectively. A subjective improvement of dysphagia was seen in 8 (40.0%), and in 14 patients (70.0%), while a radiographic improvement was recognized in 5 (25.0%) and 10 cases (50.0%) in groups A and B, respectively. In the resected specimen of 16 (group A) and 17 patients (group B), histopathological evidence of the effectiveness of the treatments were recognized in 3 (18.8%) and 7 (41.2%) from groups A and B, respectively. Excluding the cases of superficial carcinoma (T1 tumour), histologic effectiveness of the treatments were recognized in 2 (14.3%) and 7 (58.3%) in groups A and B, respectively (p < 0.05). There was no difference in the occurrence of side effects between the groups. Therefore, the clinical and pathological effects were favourable in the hyperthermia combined with chemotherapy group, especially in the cases with advanced oesophageal cancer.

Between 1985 and 1992 a total of 403 patients with resected thoracic esophageal squamous cell carcinoma were evaluated histopathologically, and various pathologic findings related to survival were examined. Concerning depth of tumor invasion, 8 (2%) cases were pTis, 110 (27%) were pT1, 48 (12%) were pT2, 202 (50%) were pT3, and 35 (9%) were pT4. Lymphatic invasion was detected in 299 cases (74%), blood vessel invasion in 200 cases (49%), intramural metastasis in 45 (11%), and lymph node metastasis in 232 (58%). In pT1 carcinoma cases, 4% of mucosal carcinomas and 30% of submucosal carcinomas had lymph node metastasis. Tumors with deeper invasion had a higher incidence of lymph node metastasis: 74% of pT3 carcinomas and 83% of pT4 carcinomas. The sites of lymph node metastasis were divided into mediastinal, cervical, and abdominal fields; and rates of lymph node metastasis were 49%, 14%, and 41%, respectively. In all resected cases, the operative mortality rate was 3.2%, and the overall 5-year survival rate was 44.8%. The 5-year survival rate of patients with curative resection (R0 and R1) was 49.5%, whereas patients with palliative resection (R2) did not survive more than 3 years. There was no significant difference in survival relative to tumor location. In curatively resected cases, the significant prognostic factors by multivariate analysis were pT category, vascular invasion, lymph node metastasis, and intramural metastasis. Prognosis of lymph node-positive cases did not depend on the positive node site. Patients with only one positive node had a better prognosis, and those with six or more positive nodes had a poor prognosis.(ABSTRACT TRUNCATED AT 250 WORDS)

Thirty-nine patients with advanced measurable squamous cell carcinomas were treated with two or more courses of 70 mg cisplatin/m2 on day 1 and 700 mg infused 5-fluorouracil/m2 on days 1-5 every 21 days. The overall response rate was 35.9 (95% confidence limits, 24.8-55.1%). Responses were seen in primary sites in the esophagus of five patients, in the lung of seven, the liver of one and the mediastinal lymph nodes of one. The average response duration was 3.5 (range 1-12) mo for patients who achieved partial response. The average survival time after the first administration was 9.5 mo for patients who responded to the treatment whereas, for those who did not, it was 5.6 mo. The major form of toxicity was myelosuppression and there were six patients with grade 3 toxicity and one with grade 4. The present study was designed to evaluate the effectiveness of combined cisplatin and 5-fluorouracil for advanced squamous cell carcinoma, and the results showed that it had a reasonable effect and might possibly be used as a postoperative chemotherapy because of its mild side effects.

We report clinico-pathological studies on the effect of preoperative hyperthermia and chemotherapy combined with radiotherapy (HCR) for progress of the local curability of advanced esophageal carcinoma. The subjects of these studies were 17 patients who underwent subtotal esophagectomy after preoperative irradiation 40 Gy from 1980 to 1989, of which 8 patients had HCR, 6 patients irradiation only (R), 3 patients both irradiation and chemotherapy (CR). The clinical response rate of the patients with R or CR was 33% (PR 3, MR 3, NC 3), and the histological effective (Ef3 or Ef2) rate was 56% (Ef3 1, Ef2 4, Ef1 4). The clinical response rate of the patients with HCR was 88% (PR 7, MR 1), and the histological effective rate was 100% (Ef3 1 Ef2 7). HCR was more effective than R or CR for the local lesion of esophageal carcinoma histopathologically (p less than 0.05). However, the survival rate of patients with HCR was similar to R and CR, respectively. These results suggest that further improvement of the heating methods and the methods of combining hyperthermia with irradiation and chemotherapy is needed.

The criteria of early carcinoma of the stomach, defined in 1981, has gained worldwide acceptance. A few proposals of a criteria for early carcinoma of the esophagus have been made; however, these criteria have not been internationally accepted, as the rate of recurrence is high in patients with early carcinoma of the esophagus, as determined by these criteria. In patients with submucosal carcinoma of the esophagus, metastasis to lymph nodes was present in 32.5 per cent at the time of the operation, and the five year survival rate was only 54.5 per cent. On the other hand, while the incidence of epithelial or mucosal carcinoma, or both, is only 2.2 per cent (46 of 2,130) in patients with carcinoma of the esophagus, the incidence has been remarkably increased and the five year cumulative survival rate for patients with epithelial carcinoma or mucosal carcinoma, or both, is now 88.4 per cent. Thus, we consider that the criteria for early carcinoma of the esophagus to be mucosal carcinoma as well as epithelial carcinoma regardless of the presence or absence of lymph node metastasis, and that a submucosal carcinoma should be excluded from the classification of early carcinoma of the esophagus.

The development of peptic ulcers in gastric tubes used for esophageal reconstruction for cancer are rare. However, they can potentially cause serious complications, including perforation and hemorrhaging. We experienced a case in which an ulcer of large size developed in the gastric tube, and it was very difficult to treat. The patient was a 72-year-old man, who had undergone an esophagotomy of the thoracic portion, an gastroesophagoplasty through the anterior portion of the sternum, and postoperative radiotherapy 2 years ago. Eight days after his admission, the ulcer began excessive bleeding, and we performed an emergency operation. The ulcer perforated into the mediastinum, and developed an abscess involving the intrathoracic artery. After hemostasis and debridement, we resected the upper half of the gastric tube, closed the oral side of the remaining portion, and converted the cervical esophageal stump into an external fistula. The wound was covered with a flap. A histological examination showed an ulcer with no evidence of malignancy, and without any signs of healing. Five months were required for the wound to heal completely. After that, we succeeded in reconstruction through jejunal free-transfer, using the microvascular surgery technique. Some pathogenesis is suggested for gastric ulcers after gastroesophagoplasty. Despite performing a vagotomy, the secretion of acid from the gastric mucosa is common. Both this condition, and the deterioration of the mucosal barrier caused by surgery, can play significant roles in the development of the ulcer. The histological influence of postoperative radiotherapy is also important, as this treatment aggravates the circulatory disturbance, and disturbs the histological reaction necessary for healing.

The Japanese Society for Esophageal Cancer has defined mucosal and submucosal cancer as superficial cancer of the esophagus. Superficial cancer without metastasis was defined as early cancer of the esophagus. Of 104 cases of superficial cancer resected in these twenty years, early cancer was 62 cases, the incidence being 4.9% of all resected cases. The operative mortality rate and 5-year-survival rate of early cancer were 1.9% and 62%, respectively. As for the depth of the cancerous invasion, 14 of 104 superficial cancer cases were mucosal cancer. Twelve of 14 mucosal cancer belonged to early cancer. Vascular invasion was noted in one of 12 early mucosal cancer cases. No cancer death has been encountered in the early mucosal cancer cases. So the discovery of the mucosal cancer is mandatory to obtain the excellent results. For this purpose the value of endoscopy including the dying method, should be emphasized. In terms of treatment of the early cancer no special surgical procedure has been considered. The lymph node dissection has been carried out systematically. Some kinds of postoperative combined treatments are performed for early cancer cases with vascular invasion. The reduction surgery and the noninvasive treatment will be advisable for the small mucosal lesions.