Toshitaka Fukumoto

Long-term results of subtotal esophagectomy with three-field lymphadenectomy for carcinoma of the thoracic esophagus.

ObjectiveThis study evaluated the impact of aggressive surgery on survival in patients with carcinoma of the thoracic esophagus. Summary Background DataPrognostic value of lymph-node status for patients with esophageal carcinoma was emphasized, although it is currently under debate whether extensive lymph node dissection improves survival. MethodsTwo hundred ninety-five patients with thoracic esophageal carcinoma were admitted to Kagoshima University Hospital from December 1982 to December 1990. Esophagectomy was performed on 244 (82.7%) of these patients; 106 of whom underwent three-field lymphadenectomy (bilateral cervical, mediastinal, and abdominal regions) were analyzed regarding lymph-node status, tumor recurrence, and the effect of prognostic factors on survival using Coxs proportional hazards model. ResultsHospital mortality and morbidity were 10.4% (11/106) and 65.1%, respectively. Seventy-eight patients (73.6%) had nodal involvement, including 49 patients with abdominal lymph-node metastases and 46 patients with recurrent nerve-node metastases. Five-year survival rates were 54.5% for 16 patients with a solitary nodal metastasis, 30.3% for stage III, 17.4% for stage IV, and 7.2% for 28 patients with six or more metastatic nodes. The most frequent sites of recurrence were the upper mediastinal region and the lung – its incidence increased significantly as the number of positive nodes increased. The most unfavorable prognostic factors included regional or recurrent nerve-node metastasis and patient age of more than 71 years. ConclusionsThree-field lymphadenectomy, including especially the removal of bilateral recurrent nerve nodes in the cervical region, is essential for improving the survival of patients with carcinoma of the upper two thirds of the thoracic esophagus.

Appraisal of Ten-Year Survival following Esophagectomy for Carcinoma of the Esophagus with Emphasis on Quality of Life

Abstract. Characteristics of 10-year survival after esophagectomy for carcinoma were studied retrospectively in 161 patients who underwent curative operation between 1973 and 1984. Of the 161 patients, 44 (27.3%) survived for 10 years after operation (right transthoracic approach with cervical anastomosis in 36 patients and left thoracoabdominal approach with jejunoesophagostomy in 8 patients). Females survived significantly longer than males; 10-year survival was observed in 10 (50%) of 20 females and 34 (24.1%) of 141 males. TNM factors were significantly linked to the 10-year survival for 25 patients (56.8%) whose tumors invaded the adventitia and 20 patients (45.5%) who had lymph node metastases, where the total number of involved nodes was less than eight. A questionnaire mailed 10 years after operation revealed that about one-fifth of the 10-year survivors could not go up one flight of stairs without taking a rest, and that the daily activity significantly deteriorated if the patient’s age at the time of surgery was more than 66 years. One-third of the 10-year survivors were not satisfied with the daily quantity of food intake, resulting in no gain of body weight after discharge from the hospital. This complaint was significantly correlated with either weekly reflux or heartburn, resulting in the increasing number of nonmalignancy deaths. Of 13 ten-year survivors who were alive at 10 years but died after that, 11 (84.6%) died of pneumonia or malnutrition. Duodenogastroesophageal reflux may eventually cause nonmalignancy death 10 years after esophagectomy for carcinoma.

Assessment of cervical lymph node metastasis in esophageal carcinoma using ultrasonography.

OBJECTIVE To evaluate the efficacy of ultrasonography for the diagnosis of cervical lymph node metastasis in esophageal carcinoma. SUMMARY BACKGROUND DATA Ultrasound (US) examination is useful for diagnosing lymph node metastasis. However, few reports have examined its role in the decision to perform cervical lymph node dissection in esophageal carcinoma. METHODS Ultrasound examination was performed to evaluate cervical lymph node metastasis in 519 patients with esophageal carcinoma. The patients were divided into 5 groups according to treatment received: group 1, 153 patients who underwent curative resection of primary tumor by right thoracotomy and complete bilateral cervical lymphadenectomy; group 2, 112 patients who underwent curative resection of primary tumor by right thoracotomy but without cervical lymphadenectomy; group 3, 78 patients who underwent esophagectomy by left thoracotomy or blunt dissection with or without removal of cervical lymph nodes; group 4, 76 patients with palliative resection without cervical lymphadenectomy; and group 5, 100 patients without any surgical treatment. US diagnosis was compared with histologic findings or cervical lymph node recurrence. RESULTS Lymph node metastasis was detected in 30.8% of patients (160/519). The sensitivity, specificity, and accuracy of US diagnosis in group 1 were 74.5%, 94.1%, and 87.6%, respectively. Cervical lymph node recurrence was seen in 7 patients (4.6%) in group 1, in 4 patients (3.6%) in group 2, and 3 patients (3.8%) in group 3. Although the incidence of cervical lymph node metastasis as determined by US examination was high in groups 4 and 5, almost none of the patients died of cervical lymph node metastasis. CONCLUSIONS Ultrasound examination plays a useful role in the decision to perform cervical lymph node dissection in patients with esophageal carcinoma, particularly in those with potentially curative dissection.

Mucosal Squamous Cell Carcinoma of the Esophagus: A Clinicopathologic Study of 30 Cases

A clinicopathologic study was carried out on 30 patients with mucosal esophageal cancer (MEC). The depth of cancer invasion was subdivided histologically into three categories: m1 = carcinoma in situ (intraepithelial carcinoma) or carcinoma with questionable invasion beyond the basal membrane; m2 = cancer invasion confined to the lamina propria, and m3 = cancer reaching to or infiltrating into the muscularis mucosae. Lymph node metastases and lymphatic invasion were found only in the tumors reaching or infiltrating the muscularis mucosae (m3). The maximum histologic vertical extent of the tumors was more than 1 mm in 4 of 5 patients with lymph node metastasis or lymphatic invasion. None of the patients died of recurrent esophageal disease, and 3 of the 6 patients who had a second primary tumor died of this other malignancy. It is critical to distinguish between m1, m2 and m3 tumors to plan a treatment strategy, including an endoscopic mucosal resection.

Lymph node and perinodal tissue tumor involvement in patients with esophagectomy and three‐field lymphadenectomy for carcinoma of the esophagus

Lymph node metastasis is a definitive prognostic factor; however, perinodal fat tumor invasion has not been fully elucidated.

Lymph node metastasis of early stage carcinoma of the esophagus and of the stomach.

We undertook a comparative histologic study of early stage carcinoma of the esophagus and stomach, with tumor invasion limited to the submucosa. Here we analyze lymph node metastasis, lymphatic invasion, and vascular invasion. Our study is based on a retrospective review of 77 patients with early stage carcinoma of the esophagus and 192 patients with early stage carcinoma of the stomach treated during the period from 1973 through 1991. The incidence of lymph node metastasis and lymphatic invasion was significantly higher in intramucosal or submucosal esophageal cancer than in intramucosal or submucosal gastric cancer. However, there was no significant difference between intramucosal esophageal cancer and submucosal gastric cancer. The metastatic site of lymph nodes in esophageal cancer tended to be distant from the location of primary tumor compared with lymph nodes invaded by gastric cancer. Lymphatic invasion and vessel invasion between submucosal esophageal cancer and submucosal gastric cancer was statistically significant. From these results, we conclude that intraepithelial or intramucosal esophageal cancer is comparable to early stage carcinoma of the stomach, whereas submucosal esophageal cancer is actually an advanced lesion.

Prophylactic action of allopurinol against chemotherapy-induced stomatitis--inhibition of superoxide dismutase and proteases.

The activities of superoxide dismutase (SOD) and several proteases were measured in kidney of mice treated with allopurinol in order to elucidate the mechanism of prophylactic action of allopurinol against chemotherapy-induced stomatitis. The following results were obtained. Following 3 day administration of allopurinol 20 mg/day per os (Group C), the concentrations of allopurinol and oxipurinol in the renal tissue were 203.9 ± 52.1 and 1141.7 ± 194.8 μg/g, respectively. The SOD activity was significantly lower in Group C than in the untreated control group (p < 0.01). The enzyme activities of papain and trypsin were suppressed in Group C. However, the other proteases tested were not affected by the administration of allopurinol, indicating only weak anti-protease action of allopurinol. These results suggest that allopurinol may be effective to prevent chemotherapy-associated stomatitis via both direct and indirect actions to oral mucosa, that include inhibitory actions on xanthine oxidase as well as protease.

Does preoperative chemotherapy cause adverse effects on the perioperative course of patients undergoing esophagectomy for carcinoma

The aim of this study was to clarify whether preoperative chemotherapy caused adverse effects on the perioperative course of patients undergoing esophagectomy. A total of 42 esophageal cancer patients were entered into a randomized trial and were analyzed. Twenty-one patients were assigned to immediate surgery (Surgery Group). The other 21 received two 5-day courses of chemotherapy comprising cisplatin (70 mg/m2) on day 1, and fluorouracil (700 mg/m2) and leucovorin (20 mg/m2) on each of days 1 to 5 (chemotherapy group). Hospital mortality comprised of one patient (2.3%) who had undergone an operation in the beginning of this series at 21 days after chemotherapy. Thereafter, the interval between the chemotherapy and operation was prolonged, with the average being 35 +/- 7 days. Preoperatively, both the lymphocyte counts and serum albumin levels were not increased in the chemotherapy group of patients even though their body weights increased. In the chemotherapy group, the operation time and the blood loss were increased and, on the 1st postoperative day, the development of systemic inflammatory response syndrome was high but the level of C-reactive protein was low. The incidence of positive microbial cultures of sputum and/or wound discharge within 8 postoperative days was higher in the chemotherapy group (42.9%) than in the surgery group (4.8%). The host defense damage caused by chemotherapy may be prolonged and may show adverse effects in patients undergoing esophagectomy in the early postoperative period. Minimally, a 4-week interval between the completion of chemotherapy and operation is recommended for preventing surgical mortality related to the preoperative chemotherapy.

Lymph node metastasis and the recurrence of esophageal carcinoma with emphasis on lymphadenectomy in the neck and superior mediastinum

A series of 335 patients with squamous cell carcinoma of the thoracic esophagus undergoing resection and reconstruction via a right thoracotomy and laparotomy with cervical anastomosis between 1973 and 1990, were reviewed. Prior to 1982, the removal of lymph nodes was limited to the nodes in the mediastinum below the tracheal bifurcation and upper abdomen (142 patients). Nodal metastases were found in 89 of these patients at operation. The upper abdominal nodes were the most frequent sites of metastasis (47.2%). None of the 38 patients with positive nodes sampled from the neck and superior mediastinum survived for more than 45 months. In the 50 patients with recurrences, 30 were in the neck and/or superior mediastinum. During or after 1983, the superior mediastinal nodes, particularly the bilateral recurrent nerve nodal chains, were routinely removed (193 patients). Nodal metastasis was proven in 131 of the 193 patients, in whom 87 (45.1%) had metastasis in the neck and superior mediastinum. Eleven of these 87 patients survived for 45 months or more. In the 61 patients with recurrences, 20 were in the neck and/or superior mediastinum. These data suggest that recurrent nerve nodal chains should be removed to improve survival in patients with esophageal carcinoma.

The role of neoadjuvant radiochemotherapy using low-dose fraction cisplatin and 5-fluorouracil in patients with carcinoma of the esophagus.

OBJECTIVE We clarified the role of neoadjuvant radiochemotherapy in patients with carcinoma of the esophagus and compared it to neoadjuvant chemotherapy. METHODS We retrospectively examined 40 patients diagnosed with advanced thoracic esophageal carcinoma who underwent neoadjuvant therapy followed by esophagectomy between 1993 and 1999. We divided them into 2 groups: radiochemotherapy (17) and chemotherapy (23). Radiochemotherapy patients underwent 40 Gy radiation and low-dose fraction cisplatin (7 mg/body/day, 5 days a week x 4 weeks) and 5-fluorouracil (350 mg/body/day x 28 days). Chemotherapy patients received high-dose fraction cisplatin/5-fluorouracil involving 2 courses of cisplatin (70 mg/m2/day on day 1) and 5-fluorouracil (700 mg/m2/day on days 1-5). RESULTS Complete pathological response was 17.6% in the radiochemotherapy group and 0% in the chemotherapy group respectively. No hospital mortality occurred in the radiochemotherapy group, and 1 of the 23 chemotherapy patients died in the hospital due to postoperative complications. The incidence of residual tumors was significantly higher in the chemotherapy group (34.8%) than in the radiochemotherapy group (0%). Actuarial survival in the radiochemotherapy group at 1 year was 80.2% and at 3 years 53.5%. Actuarial survival in the chemotherapy group at 1 year was 56.5% and at 3 years 30.4%. CONCLUSIONS Histological effectiveness was greater in patients treated with preoperative radiochemotherapy than those treated with preoperative chemotherapy. The combination of radiation and low-dose fraction CDDP/5-FU thus is first choice in neoadjuvant radiochemotherapy for the advanced esophageal carcinoma.