Kikuo Aizawa

ALPHA -FETOPROTEIN PRODUCING GASTRIC CARCINOMAS : A COMPARATIVE STUDY OF THREE DIFFERENT SUBTYPES

Nine cases of gastric carcinoma with excessive production of α‐fetoprotein (AFP) were analyzed morphologically, histochemically and biochemically. Consequently, it was proposed that AFP‐producing gastric carcinomas should be divided into three subtypes: (i) hepatoid type; (ii) yolk sac tumor‐like type; and (iii) fetal gastrointestinal type. The data from the study suggested that the hepatoid type and the yolk sac tumor‐like type are derived from liver cell metaplasia and yolk sac cell metaplasia of common poorly differentiated medullary adenocarcinoma, respectively. The fetal gastrointestinal type seemed to be a result of the imitation of fetal gastrointestinal epithelium by common tubular adenocarcinoma. The hepatoid type was also the most common in the file of AFP‐producing gastric carcinoma. Unfortunately, most of the hepatoid types seemed to be highly malignant.

Tumor spread and outcome of treatment in primary esophageal small cell carcinoma

The most effective treatment for patients with esophageal small cell carcinoma has not yet been established because of the overall extremely poor prognosis regardless of the mode of treatment. The role of esophagectomy has been controversial in the management of patients with this disease.

Intramural Metastases from Thoracic Esophageal Cancer: Local Indicators of Advanced Disease

Abstract. The patterns of tumor spread and long-term survival of patients with (n = 54) and without (n = 270) intramural metastasis from esophageal cancer were investigated after either extended radical (n = 155) or less radical (n = 169) esophagectomy. The purpose was to evaluate whether extended radical esophagectomy has an impact on the long-term survival of patients with intramural metastases from the disease. The patients with intramural metastasis had significantly larger primary tumors (p < 0.01) and more frequent T4 tumors (p < 0.001), stage IV disease (p < 0.05), lymphatic invasion (p < 0.05), and lymph node metastasis (p < 0.01) than did those without intramural metastasis. The survival rates of patients with intramural metastases were significantly worse than those of patients without intramural metastases after resection (p < 0.001). No patient with intramural metastases survived more than 4 years after either extended or less radical esophagectomy, and there was no significant difference between the two survival curves. Therefore intramural metastases should be considered local indicators of advanced esophageal cancer, and radical esophagectomy may not be indicated for patients with intramural metastasis from the disease.

Histogenesis of hepatoid adenocarcinoma of the stomach: molecular evidence of identical origin with coexistent tubular adenocarcinoma.

Hepatoid adenocarcinoma of the stomach is a highly malignant neoplasm. Most gastric hepatoid adenocarcinomas coexist with tubular adenocarcinoma. However, the relationship between hepatoid adenocarcinoma and tubular adenocarcinoma is still unclear. In the present study, the characteristics of the coexistent tubular adenocarcinomas were determined by examining their profiles of mucin production. Subsequently, molecular pathological techniques were applied to determine the clonality of 15 mixed hepatoid and tubular adenocarcinomas of the stomach. Mucin analysis suggested that the coexistent tubular adenocarcinomas with hepatoid adenocarcinoma were of the intestinal type. The patterns of chromosome X inactivation were identical between the hepatoid adenocarcinoma component and tubular adenocarcinoma component in all of 3 informative female cases. Mutations in the p53 gene were found in 5 cases. The sequences were identical within both tumor components in all 5 cases. Microsatellite analysis indicated more than 3 common patterns of loss of heterozygosity in 8 cases. These observations strongly suggested that hepatoid adenocarcinomas were of identical origin to coexistent tubular adenocarcinomas.

Coexistence of choriocarcinoma and hepatoid adenocarcinoma in the stomach

The case is presented of a 46 year old woman who had a gastric tumor with components of choriocarcinoma, hepatoid adenocarcinoma and common types of adenocarcinoma. Although two histologic types of tumor producing carcinoplacental or carcinofetal proteins were contained within the tumor, immunohistochemical analyses, especially of placental alkaline phosphatase, clearly showed that each component was present separately within the same tumor. It was only hepatoid adenocarcinoma cells that permeated the lymph and blood vessels. After the recurrence, the serum level of alpha‐fetoprotein (AFP) markedly elevated, but that of human chorlonlc gonadotropin β‐subunit (hCG‐β) was always within normal range. These findings Indicate that in the present case the hepatoid adenocarcinoma component was more aggressive in growth than the choriocarcinoma component.

Primary Small Cell Carcinoma of the Esophagus: Report of a Case

A case of esophageal small cell carcinoma successfully treated with combination therapy consisting of both pre- and postoperative chemotherapy as well as surgical resection is presented. A 74-year-old man presented with a small cell carcinoma measuring 11 cm in diameter in the lower half of his thoracic esophagus. After undergoing preoperative chemotherapy with cisplatin (25 mg, iv, days 1 through 5), the gross tumor completely regressed. However, a microscopic focus of residual cancer showing squamous cell carcinoma was found in the resected esophageal specimen. The patient received an additional two courses of postoperative chemotherapy with cisplatin (75 mg, iv monthly). He has since survived more than 9 years with no evidence of recurrent disease. We herein report a rare case of a patient with esophageal small cell carcinoma who demonstrated a complete cure.

EVALUATING THE RATIONAL EXTENT OF DISSECTION IN RADICAL ESOPHAGECTOMY FOR INVASIVE CARCINOMA OF THE THORACIC ESOPHAGUS

To define the rational extent of dissection in radical esophagectomy for esophageal cancer, survival was studied according to nodal status in 154 patients undergoing extended radical esophagectomy. The incidence of cervical metastasis in patients with upper or middle esophageal tumors did not differ between those with favorable (grade N ≤ 4) or unfavorable (grade N ≥ 5) lymph node status, at 28.6% vs 20%, respectively. On the other hand, in patients with lower esophageal tumors, the incidence of cervical metastasis was significantly lower in those with favorable grade (grade N ≤ 4) node status than in those with unfavorable grade (grade N ≥ 5) node status, at 6.5% vs 46.7%, respectively. Survival did not differ in patients with upper or middle esophageal tumors according to whether they had regional (n = 42) or distant (n = 15) lymph node metastases, the 5-year survival rates being 11.6% vs 25%, respectively. However, in patients with lower esophageal tumors, none of 10 patients with distant node metastases survived for more than 4 years, whereas the survival rate was 43.7% at 5 years for 36 patients with regional node metastases. These results show that cervical lymphadenectomy should only be performed as part of radical esophagectomy in those patients with upper or middle esophageal cancer.

Primary small cell carcinoma of the esophagus with ectopic gastrin production. Report of a case and review of the literature.

SummaryA case of primary small cell carcinoma of the esophagus in which extensive hormonal studies could be performed is reported. The tumor was considered as a neuroendocrine tumor because the tumor cells showed intracytoplasmic argyrophilia, neurosecretory granules, and positive stain for neuron-specific enolase with Grimelius stain, electron microscopy, and immunohistochemistry, respectively. Furthermore, the tumor was regarded as a gastrin-producing tumor because of positive stain for gastrin in the tumor cells. The present case is the esophagus with ectopic gastrin production.

Placental alkaline phosphatase-like isoenzymes produced by human gastric cancer cells.

The human gastric cancer cell lines, MKN1 and SCH, were biochemically and biologically characterized according to the monophenotypic expression of placental alkaline phosphatase (PLAP)‐ like enzymes. The MKN1 cell line, derived from adenosquamous carcinoma, showed the same enzyme properties as the Regan isoenzyme, whereas the SCH cell line, derived from primary gastric choriocarcinoma, had properties identical with the Nagao isoenzyme. Regan isoenzyme activity expressed by MKN1 cells was stimulated by glucocorticoid and suppressed by retinoic acid. Both agents had no significant effect on SCH cells. On the other hand, Nagao isoenzyme activity expressed by SCH cells was stimulated by sodium butyrate, which had no stimulatory effect on MKN1 cells. Moreover, the PLAP like activity of MKN1 cells showed no observable relationship to human chorionic gonadotropin (hCG) producibility. Whereas expression of the Nagao isoenzyme by the SCH cell line is presumably a result of functional differentiation in the trophoblastic direction, that of the Regan isoenzyme by the MKN1 cell line is probably not. Perhaps the Regan isoenzyme is related to carcinogenesis. Acta Pathol Jpn 39: 630 637, 1989.

ESOPHAGEAL INTRAMURAL METASTASIS FROM AN ADENOCARCINOMA OF THE GASTRIC CARDIA : REPORT OF A CASE

We report herein the rare case of a 65-year-old man found to have esophageal intramural metastasis from cancer of the gastric cardia. Endoscopic examination initially revealed an infiltrating ulcerative tumor of the gastric cardia involving the esophagogastric junction, as well as a submucosal tumor of the lower esophagus. A total thoracic esophagogastrectomy with lower mediastinal lymphadenectomy was performed, and the resected specimen demonstrated that both the cardia and esophageal tumors were adenocarcinomas with the same cellular differentiation. As lymphatic invasion and metastases to the paracardial and mediastinal lymph nodes were observed, the esophageal submucosal tumor was considered to be an intramural metastasis from the carcinoma of the gastric cardia resulting from extensive lymphatic spread. The patient died of recurrent disease 9 months after the resection. This case report serves to demonstrate that intramural metastasis may be a local indicator of the systemic spread of disease in patients with gastric carcinoma, as it is in esophageal carcinoma.