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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
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
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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