The Pyloric Sphincteric Cylinder in Health and Disease

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Chapter 33 (page 172)

Duodenal Spread and Brunner's Glands

Castleman (l936) did not describe his 21 cases with microscopic duodenal spread individually. He noted that spread had generally taken place deep to Brunner's glands, i.e. between the glands and the muscularis externa. On examining the accompanying illustrations, it appears if Brunner's glands were not involved.

In 14 cases with duodenal extension Eker and Efskind (l952) stated that the distance of duodenal spread beyond Brunner's glands was short in all. Six of the cases were gastric adenocarcinomas, and in these spread in the duodenal mucous membrane stopped at the point where Brunner's glands commenced. (In the remaining 8 cases of mucinous scirrhus and colloid carcinomas no mention was made of Brunner's glands).

Paramanandhan (l967) noted in 29 necropsy specimens that Brunner's glands were often compressed by dilated lymphatics containing tumor cells. He stated that the glands themselves appeared to be particularly resistant to gastric carcinoma spreading across the pylorus.

In our 7 cases Brunner's glands were stated to be free of tumor cells in 4 (3 cases of poorly and one of well differentiated adenocarcinoma). In 3 cases no comment was given on Brunner's glands; the extent of spread in these cases was 2.0 cm, 2.0 cm and 2.0 mm respectively. It is concluded that there appears to be a possibility that Brunner's glands are resistant to the spread of gastric adenocarcinoma across the pylorus.

Epidermal Growth Factor in Gastric Carcinoma

Epidermal growth factor (EGF) and homologous alpha-tumor growth factor are mitogenic polypeptides which act by binding to epidermal growth factor receptors (EGFR). Pfeiffer et al. (l990) investigated whether increased production of EGF or increased density of EGFR may occur in gastric carcinomas as compared with normal mucosal tissue. The EGF binding capacity was found to be significantly higher in carcinomas than in normal mucosa. In 15 cases of gastric carcinoma EGFR showed an increase in 9, a decrease in 2 and no change as compared with normals in 3. In a case of mucinous adenocarcinoma there was an extreme, 320-fold increase of EGFR. In 2 of 22 carcinomas EGF activity was increased. It was concluded that a relative overexpression of EGFR occurs in some cases of gastric carcinoma.

Lee et al. (l989, l991) using a retrospective immunohistochemical evaluation for EGF and EGFR in 167 cases of benign and malignant gastric disease, made similar observations. In approximately 20 percent of gastric carcinomas increased amounts of EGF and EGFR were detected in the tumor as well as the adjacent mucosa, the intratumor values being significantly higher than the mucosal. Overexpression of EGF and EGFR was found to identify a definite subgroup of gastric carcinomas; tumors in this subgroup appeared to be deeply invasive.

Brunner's Glands and Epidermal Growth Factor

Epidermal growth factor is described as a polypeptide present in human urine, probably playing some role in the regulation of cell growth; it was originally found to inhibit gastric acid secretion and was called urogastrone (Pfeiffer et al. l990). An EGF homologous protein called alpha tumor growth factor may be produced in high amounts by transformed cells. It binds to the EGF receptor and has activities similar to EGF (Pfeiffer et al. l990).

Lee et al. (l989, 1991) and Pfeiffer et al. (l990) seem to implicate EGF in the pathogenesis of a subgroup of gastric carcinomas. These authors did not mention possible involvement of Brunner's glands. It has been shown (Chap. 4) that in man Brunner's glands secrete EGF (Elder et al l978; Heitz et al. l978). EGF is also produced in the submandibular salivary glands (Hollenberg l979). Mouse EGF and human urogastrone are closely related structures and seem to be identical in biologic activity; data on human EGF suggest that it is urogastrone. Experimentally both substances are powerful mitogens (Elder et al. l978), increasing the synthesis and contents of DNA and RNA in the gastroduodenal mucosa (Dembinsky et al. l982).

Kirkegaard et al. (l98l, l983) demonstrated a dense network of vasoactive intestinal polypeptide (VIP) immunoreactive nerve fibres around the acini of Brunner's glands. According to Ferri et al. (l984) few of these fibres enter the glands to reach the acinar cells in cases of gastric carcinoma. Skov Olsen et al. (l985) pointed out that cholinergic, adrenergic and VIP-containing nerves innervate and thereby influence secretion from Brunner's glands; VIP was found to increase the secretion and total output of EGF.

Whether there is a relationship between Brunner's glands and some types of pyloric adenocarcinoma is speculative. Too few cases have been studied for firm conclusions; however, available evidence suggests that an association cannot be excluded. On the one hand Brunner's glands seem to escape direct infiltration in duodenal spread of some cases of pyloric adenocarcinoma. On the other hand overexpression of EGF, which is produced by Brunner's glands (and by the submandibular salivary glands) may occur in subgroups of gastric carcinoma.

The fate of APUD cells in the pyloric mucosal zone in cases of pyloric carcinoma, is not known.

Conclusion: Pyloric Carcinoma, Brunner's Glands and Epidermal Growth Factor

It appears that Brunner's glands of the duodenum may be resistant to pyloric adenocarcinoma spreading across the pylorus (Eker and Efskind 1952, Paramanandhan 1967, Keet 1993). However, further patho-anatomical studies would be necessary to confirm this finding.

Overexpression of EGF, which is produced by Brunner's glands (and by the submandibular salivary glands) may occur in subgroups of gastric carcinoma. The exact relationships between pyloric carcinoma, Brunner's glands and EGF remain to be elucidated.

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