Hiroko Ide

Surgery Plus Chemotherapy Compared With Surgery Alone for Localized Squamous Cell Carcinoma of the Thoracic Esophagus: A Japan Clinical Oncology Group Study—JCOG9204

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.

A randomized trial of surgery with and without chemotherapy for localized squamous carcinoma of the thoracic esophagus: The Japan clinical oncology group study

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.

Small ultrasonic probes for determination of the depth of superficial esophageal 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.

Evaluation of the accuracy of preoperative staging in thoracic esophageal cancer.

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.

Cytophotometric dna analysis of mucosal and submucosal carcinoma of the esophagus

Cell nuclear deoxyribonucleic acid (DNA) content was microspectrophotometrically determined in 35 cases of mucosal and submucosal carcinoma of the esophagus. DNA distribution pattern was classified into types I, II, III, and IV, according to the degree of dispersion on the DNA histogram, in the order of wider distribution. Patients with types I and II (relatively regular in DNA distribution) had an uneventful postoperative course and no recurrence, whereas 3 of 15 (20%), and 5 of 9 (55.6%) with type III and type IV, respectively (widely scattered DNA distribution), died following a recurrence. Cytophotometric DNA analysis of the cancer cells reflected well the outcome in patients with esophageal carcinoma. These results suggest the potential usefulness of cytophotometric DNA analysis for assessing the prognosis, even in the early stage of esophageal carcinoma.

Evaluation of endoscopic ultrasonography for the diagnosis of submucosal tumors of the esophagus

SummaryEndoscopic ultrasonography was carried out on 55 patients whose X-ray films or endoscopic examinations indicated the presence of a submucosal tumor. Endoscopic ultrasonography revealed 8 cases of extraluminal compression and 48 cases of submucosal tumors. Histological studies were performed on 29 cases with submucosal tumors. In 28 of the 29 cases (97%) the location of the tumor in the esophageal wall was correctly estimated ultrasonographically, and appropriate treatment was selected. Tumors ranging from 3 to 50 mm in diameter could be measured accurately. This method may be helpful in follow-up studies. Endoscopic ultrasonographic findings, such as characteristics of the tumor border and internal echoes, were studied to predict the histological diagnosis of the tumor. Leiomyoma, cyst, granular cell tumor, lipoma, and intraluminal metastasis of esophageal cancer were all found to have specific ultrasonographic findings indicating the histological nature of the tumor.

CYFRA 21-1 as a tumor marker for squamous cell carcinoma of the esophagus.

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.

Thoracic and cardiovascular surgery in Japan during 1998

of the Survey We sent out survey questionnaire forms to Departments of each category in all 1,004 institutions nationwide in early April 2000. Form sent out and received back by the end of December 2000 Sent out Returned Response rate (A) Cardiovascular surgery 496 457 92.1% (B) Respiratory surgery 654 595 91.0% (C) Esophageal surgery 667 576 86.4% Categories subclassified according to the number of operations performed

Analysis of postoperative complications after esophagectomy for esophageal cancer in patients receiving neoadjuvant therapy.

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.

Radiotherapy for superficial esophageal cancer

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 Womens 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.