Otsuo Tanaka

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.

A Phase II Trial of Chemoradiotherapy for Stage I Esophageal Squamous Cell Carcinoma: Japan Clinical Oncology Group Study (JCOG9708)

OBJECTIVE The study objective was to evaluate the efficacy and toxicity of chemoradiotherapy with 5-fluorouracil (5-FU) plus cisplatin in patients with Stage I esophageal squamous cell carcinoma (ESCC). The primary endpoint was proportion of complete response (%CR). METHODS Patients with Stage I (T1N0M0) ESCC, aged 20-75 years, without indication of endoscopic mucosal resection were eligible. Treatment consisted of cisplatin 70 mg/m(2) (day 1) and 5-FU 700 mg/m(2)/day (days 1-4) combined with 30 Gy radiotherapy (2 Gy/day, 5 days/week, days 1-21). The cycle was repeated twice with 1-week split. Salvage surgery was recommended for residual tumor or local recurrence. RESULTS From December 1997 to June 2000, 72 patients were enrolled. No ineligible patient or major protocol violation was observed. There were 63 CRs for %CR of 87.5% [95% confidence interval (CI): 77.6-94.1]. Six patients with residual tumor successfully underwent esophagectomy. There was no Grade 4 toxicity. Four-year survival proportion was 80.5% (95% CI: 71.3-89.7), and 4-year major relapse-free survival proportion was 68% (95% CI: 57.3-78.8) (mucosal recurrence removed by endoscopy was not counted as an event). CONCLUSIONS High CR proportion and survival proportion with mild toxicity suggest that this regimen could be considered as a candidate of new standard treatment to be compared with surgery in patients with Stage I ESCC.

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.

Comprehensive Registry of Esophageal Cancer in Japan, 2003

We are very pleased to publish the Comprehensive Registry of Esophageal Cancer in Japan, 2003, and thank all the members of the Japan Esophageal Society who made great contributions in preparing this material. We would like to review the history of the registry of esophageal cancer cases in Japan. The Registration Committee for Esophageal Cancer, the Japan Esophageal Society, has annually registered cases of esophageal cancer since 1976 and published the first issue of the Comprehensive Registry of Esophageal Cancer in Japan in 1979. The Act for the Protection of Personal Information was promulgated in 2003, and began to be enforced in 2005. The purpose of this Act is to protect the rights and interests of individuals while taking into consideration the usefulness of personal information, keeping in mind the remarkable increase in the use of personal information arising from the development of today’s advanced information and communications society. The registry of esophageal cancer cases has required some adjustments to comply with the Acts. The new registration system has been discussed for several years and was finally completed in 2008. The most important point was These data were first issued on 1 March, 2011, as the Comprehensive Registry of Esophageal Cancer in Japan, 2003. Not all pages are reprinted here; however, the original table and figure numbers have been kept. The authors were at the time members of the Registration Committee for Esophageal Cancer, the Japan Esophageal Society, and made great contributions in preparing this material.

Electrogastrography prior to and following total gastrectomy, subtotal gastrectomy and gastric tube formation

On electrogastrography (EGG) spectral analysis, an activity of 3 cycles per minute (cpm) is supposed to be specific for the stomach. After total or subtotal gastrectomy, the original site of the stomach is occupied mainly by the intestine. We attempted to determine if intestinal activity could be recorded in this region with EGG. Epigastric recordings were performed in patients prior and following gastrointestinal or control surgeries. Spectral analysis, using the maximal entropy method and ensemble means was applied to data analysis from these recordings. Preoperatively, the majority of the power peaks were found around 3, 6, and 11 cpm. The postprandial-to-fasting power ratio of all of these power peaks increased significantly postprandially (P<0.05–0.01). Following total gastrectomy, the power peak around 3 cpm disappeared or was significantly diminished in amplitude (P<0.05). The postoperative-to-preoperative power ratio ranged from 0.03 to 0.10 (P<0.001–0.01). However, the power peak around 11 cpm did not significantly change prior to or following total gastrectomy, and the 11 cpm peak appeared relatively dominant. Simultaneous manometric studies in the Roux limb demonstrated a correlation between the power spectral frequency of EGG and manometry at 11 cpm. Therefore, the 11 cpm peak appeared to reflect jejunal or Roux limb electrical activity. The postoperative to preoperative power ratio for the 3 cpm also was significantly reduced following subtotal gastrectomy and gastric tube formation in patients in the postprandial state (P<0.05–0.001).

Superficial spreading carcinoma of the esophagus

Superficial spreading type of carcinoma of the esophagus was defined as lesions with an intramucosal extension of carcinoma 20 mm or more from the main lesion. Eleven (6.1%) of 179 cases were thus selected for this investigation. These cases were further divided into two groups: Group A, consisting of four cases (2.2%) with the main lesion confined to the submucosa, representing a relatively early stage; and Group B, consisting of seven cases (3.9%) with the main lesion invading the muscular layer or deeper. One of the most characteristic features in the four cases belonging to Group A was an unexpectedly high incidence of lymphatic permeation and lymph node metastases leading to a poor prognosis. Another feature that may be important, particularly for surgeons performing esophagectomy, was the difficulty in deciding the proximal resection line of the esophagus because the boundaries between involved and uninvolved portions were frequently indistinguishable in this particular pathologic entity, not only in Group A but in Group B.

Comprehensive Registry of Esophageal Cancer in Japan, 2002

We are very pleased to publish the Comprehensive Registry of Esophageal Cancer in Japan, 2002, we thank all the members of the Japan Esophageal Society who made great contributions in preparing this material. First of all, we describe the history of the registry of esophageal cancer cases in Japan. The Registration Committee for Esophageal Cancer of the Japan Esophageal Society, has registered cases of esophageal cancer since 1976 and published the fi rst issue of the Comprehensive Registry of Esophageal Cancer in Japan in 1979. The Act for the Protection of Personal Information was promulgated in 2003, and began to be enforced in 2005. The purpose of this Act is to protect the rights and interests of individuals while taking into consideration the usefulness of personal information, keeping in mind the remarkable increase in the use of personal information arising from the development of today’s advanced information and communications society. The registry of esophageal cancer cases has required some improvements to comply with the Acts. The new registration system has been considered for several years and was fi nally completed in 2008. The most important point was “anonymity in an unlinkable fashion” using encryption with a “hash function”. Finally, the registry resumed registering cases of esophageal cancer that had been treated in 2001. We briefl y summarized the Comprehensive Registry of Esophageal Cancer in Japan, 2002. A total of 4281 cases were registered from 222 institutions in Japan. As for the histologic type of cancer according to biopsy specimens, squamous cell carcinoma and adenocarcinoma accounted for 92.9% and 2.4%, respectively. Regarding clinical results, the 5-year survival rates of patients treated using endoscopic mucosal resection, concurrent chemoradiotherapy, radiotherapy alone, chemotherapy alone, or esophagectomy were 87.7%, 22.9%, 15.1%, 1.7%, and 44.1%, respectively. Concerning the approach used to perform an esophagectomy, 16.5% of the cases were performed endoscopically, that is, thoracoscopically, laparoscopically, or mediastinoscopically. Regarding the reconstruction route, the retrosternal, the posterior mediastinal and the intrathoracic route were used in 35.4%, 32.4% and 17.9% of cases, respectively. The percentage of operative deaths occurring within 30 days or less after operation and the percentage of postoperative hospital deaths occurring 31 days or more after operation were 1.2% (25 out of 2028 cases) and 2.0% (41 out of 2028 cases), respectively. We hope that this Comprehensive Registry of Esophageal Cancer in Japan for 2002 helps to improve all aspects of the diagnosis and treatment of esophageal cancer.

Operative treatment for metachronous pulmonary metastasis from esophageal carcinoma

BACKGROUND The clinical significance of operative treatment for metachronous pulmonary metastasis from esophageal carcinoma is unclear. METHODS We retrospectively reviewed 23 consecutive patients who underwent operative resection for metachronous pulmonary metastasis from esophageal carcinoma from 1991 to 2008. Patient baseline characteristics, survival probability, and prognostic factors were analyzed. The median follow-up period was 31 months for surviving patients. RESULTS There were 19 men and 4 women, with a median age of 66 years at the time of pulmonary resection. The median disease-free interval was 15.5 months. Cervical or mediastinal lymph node metastases preceded pulmonary metastases in 4 patients. Seven patients (30.4%) had multiple metastases with a maximum number of 4. The median operative time and blood loss were 94.5 minutes and 18 mL, respectively. The median length of postoperative stay was 12.5 days. The predicted 1-, 3-, and 5-year survival rates using the Kaplan-Meier method were 73.9%, 43.5%, and 43.5%, respectively, with a median survival time of 28.7 months. Univariate analysis revealed that an extrapulmonary metastasis as the initial recurrence site was an unfavorable prognostic factor (P = .0411). Multivariate analyses, however, did not identify the initial recurrence site as an independent prognostic factor (P = .0542). CONCLUSION Operative resection for metachronous pulmonary metastasis from esophageal carcinoma is an acceptable treatment. This study of a limited number of patients may have created a constitutional selection bias. An antecedent extrapulmonary metastasis was found to be an unfavorable prognostic factor.

Role of preoperative administration of Bleomycin and radiation in the treatment of esophageal cancer

The preoperative use of Bleomycin (BLM) alone or combined with irradiation in the treatment of esophageal cancer was evaluated in 58 patients who underwent surgical removal of the lesion for the past three and a half years. Histologic study showed such preoperative treatment is effective in inducing favorable changes in neoplastic cells in 69 per cent (40/58) of the primary lesions and in a significant number of involved lymph nodes of the second or the third groups. The study clearly suggests that preoperative Bleomycin administration combined with irradiation may be an useful adjunct preoperative procedure in esophageal cancer.