Sumio Saito

Yolk sac tumor (endodermal sinus tumor) and alpha-fetoprotein. A report of three cases.

Three instances of malignant teratomas with positive reaction for alpha‐fetoprotein (AFP) are presented. Sequential evaluations in them revealed that the production rate of AFP closely paralleled the amount of the viable malignant tumor tissue which fluctuated in the course of the diseases. Two of these tumors originated in the testis and a third in the presacral region. The microscopic sections of these malignant teratomas were carefully reviewed and it was concluded that they are properly classified as yolk sac tumor or endodermal sinus tumor. The occurrence of AFP in these tumors is best explained by the yolk sac notion, because it is known that large amounts of AFP are synthesized not only by the fetal liver, but also by the yolk sac at early embryogenesis. This phenomenon will conversely lend an additional support to the morphologic contention that these tumors are of yolk sac origin and deserves further investigation.

Evaluation of alpha-fetoprotein in early infancy*

Serum AFP concentrations of normal subjects were statistically analyzed in order to obtain the normal ranges in early infancy. The 95% prediction band would seem to offer a convenient means of evaluating serum AFP in the age range 0-300 days of life. Some illustrative cases, whose AFP values were formerly considered to be abnormally high but later proved to be within normal range, are presented.

Congenital esophageal stenosis due to tracheobronchial remnants and its associated anomalies

Two cases of congenital esophageal stenosis due to tracheobronchial remnants are reported, one accompanied by anovestibular fistula and the other by microphthalmos with iris coloboma. A survey of congenital esophageal stenosis due to tracheobronchial remnants in Japan revealed that the incidence of associated anomalies in this lesion is 17.3% This value is significantly lower than that reported for esophageal atresia. Our analysis showed that esophageal atresia is the most frequently associated anomaly, followed by anorectal abnormalities. Cardiovascular anomalies are very uncommon. Embryology relating to this subject is discussed.

The endoscopic and surgical management of pyriform sinus fistulae in infants and children

Congenital pyriform sinus fistula, an embryonic remnant of the third pharyngeal pouch, is a newly recognized entity that leads to acute cervical abscess. Nine cases were reported, in patients ranging from 0 to 15 years old. In all but one case, the fistula occurred on the left side. Prior to surgery, the patients were subjected to microlaryngoscopy to identify an internal orifice and to leave a Fogarty catheter in place. Subsequent surgical ligation of the fistula was performed with this catheter as a guide. In patients with repeated infection, such a technique is mandatory for the success of surgery.

Congenital esophageal stenosis due to tracheobronchial remnants.

Abstract Three cases of esophageal stenosis due to intramural tracheobronchial remnants are reported. Cartilage, tracheal glands, and brachiogenic lymphepithelial tissue were found in the distal end of the esophagus. Esophageal stenosis due to these tracheobronchial remnants, although rare, accounts for some congenital distal esophageal stenosis in infancy. Branchiogenic lymphepithelial tissue, here first reported, can cause the esophageal stenosis as well as cartilage.

Double termination of the alimentary tract in females: A report of 12 cases and a literature review

Twelve female infants with double termination of the alimentary tract were reported. One patient had a high rectovaginal fistula, but in the other 11 cases the tract opened into the bowel uniformly at the level of the levator ani (anorectal-vestibular fistula). In these patients, diagnosis of the anatomical level of the fistula was made definitely with our radiological technique. Excision of not only the fistulous tract but also the anterior half of the rectum below the fistula is essential to achieve a cure without recurrence. The pathogenesis of this condition is discussed and the pertinent literature reviewed.

Alpha-fetoprotein, prealbumin, albumin, alpha-l-antitrypsin and transferrin as diagnostic and therapeutic markers for endodermal sinus tumors

According to Gitlin, alpha-fetoprotein (AFP), albumin, prealbumin, alpha-1-antitrypsin and transferrin are normal products of the human yolk sac. They are expected to reappear in human endodermal sinus tumor (yolk sac tumor). The synthesis of alpha-fetoprotein and other serum proteins by human endodermal sinus tumor was studied in the culture cells and in the tumor tissue transplanted into nude mice. The results gave evidences of synthesis of some of these proteins including alpha-fetoprotein and alpha-1-antitrypsin. Serum concentrations of these proteins were studied in eight children having endodermal sinus tumors. Serum AFP levels were abnormally high in all cases, whereas concentrations of other serum proteins were almost within normal ranges. This might be simply reflected by the fact that pre-albumin, albumin, alpha-1-antitrypsin, and transferrin are already present in large quantities in sera of normal subjects while alpha-fetoprotein is present only in a negligible quantity. Alpha-fetoprotein, as a diagnostic and therapeutic marker of endodermal sinus tumor, showed good correlation to the tumor growth. Serum AFP concentrations declined almost to 0 ng/ml with a half-life of 4 days when surgical removal was complete, whereas serum AFP decreased only to 100-200 ng/ml with radiation and chemotherapy alone.

A study on alpha-fetoprotein and endodermal sinus tumor

Abstract The phenomenon of alpha-fetoprotein production by testicular, ovarian, or sacrococcygeal teratocarcinomas is frequently observed but has not been well explained. This paper includes clinicopathologic studies of 19 cases of teratocarcinoma with positive AFP reactions. Sixteen of the 19 showed typical histologic features of endodermal sinus tumor (yolk sac tumor) of Teilum and one other was compatible with this diagnosis. 6,7 The occurrence of AFP in these tumors is best explained by the concept of endodermal sinus tumor; because it is known that large amounts of AFP are synthesized not only by the fetal liver but also by the yolk sac during early embryonic life, and because the diagnosis of endodermal sinus tumor itself implies that the tumor is of yolk sac origin morphologically. 13 More direct evidence of AFP synthesis was demonstrated by immunofluorescent technique in one of our cases. Immunofluorescence was seen only in that cell layer long defined as of yolk sac origin morphologically. Alpha-fetoprotein studies are valuable in following such patients, unless they are 1 mo of age or younger.

Tyrosine hydroxylase and choline acetyltransferase activity in human neuroblastoma correlations with clinical features

Two neurotransmitter‐synthesizing enzymes, tyrosine hydroxylase (TH) and choline acetyltransferase (CAT), were assayed in neuroblastoma tissues from 24 children, in human neuroblastoma tissues serially transplanted in nude mice, and in human neuroblastoma cells in culture. Among tissues from 24 children, five showed an adrenergic pattern with significant TH activity alone, seven showed a cholinergic pattern with significant CAT activity alone, and the remaining 12 specimens showed a “both‐active” pattern with both TH and CAT activity. Enzymatic activities were maintained through many serial passages in vitro and in nude mice. All four specimens from children under one year of age exhibited the adrenergic pattern. In general, enzymatic activity was not correlated with degree of differentiation histologically. Among four cases of paravertebral dumb‐bell type in this series, two were cholinergic, one was adrenergic, and the last was both‐active. These results suggest that dumb‐bell type tumors may arise from either sympathetic ganglia or dorsal root ganglia. This study supports the concept that neuroblastomas are a composite of adrenergic and cholinergic cells. Significant changes in the relative proportions of these two cell types were observed with time, and after extensive therapy. Different metastatic sites often exhibited important differences in enzymatic activity. These results help to account for clinical discrepancies between urinary VMA levels and tumor growth. Assays for TH and CAT can be useful for confirming a diagnosis of neuroblastoma, and have important potential for helping to clarify the natural history of neuroblastoma. Cancer 52:263‐272, 1983.

Nude mouse xenograft study for treatment of neuroblastoma: Effects of chemotherapeutic agents and surgery on tumor growth and cell kinetics

Four human neuroblastomas transplanted into nude mice were used for experimental chemotherapy and surgery, and the following results were obtained. Cyclophosphamide was the most effective for human neuroblastoma, cis-platinum being the second, among several chemotherapeutic drugs examined. Aclacinomycin A is more effective than Adriamycin. VM26 should be administered 48 to 72 hours after injection of cis-platinum, according to flow cytometric analysis. Flow cytometric analysis also disclosed that residual tumor grows most rapidly seven days after subtotal excision. However, chemotherapy is more effective in the postoperative period than it is in the preoperative period.