Ghrelin's second life - World Journal of Gastroenterology

Sitarz R et al . Gastroenterostoma as a premalignant condition
treatment for uncomplicated peptic ulcer disease became
rare, but operations for complications of peptic ulcer
disease such as perforation, bleeding or gastric outlet obstruction
are still regularly performed. The rise of the use
of nonsteroidal anti-inflammatory drugs explains part of
this occurrence [13-16] . In Eastern Europe, the prevalence
of surgery for benign gastroduodenal ulcers remained
higher for a longer time than in Western Europe. In Poland
for example, several thousand complicated as well as
chronic peptic ulcer patients were still operated upon [17-20] ,
and there, the introduction of of antisecretory drugs occurred
in the late 1980s [21] . Nevertheless, complications
of peptic ulcer surgery will presumably become less important
there as a public health problem [22] .
HISTOPATHOLOGY
Billroth antrectomy and its various modifications remove
the part where the ulcer is located and that contains the
gastrin-producing antral mucosa responsible for the stimulation
of acid production through the oxyntic mucosa.
It also induces biliary reflux, felt to be beneficial for healing
due to its alkaline contents. The majority of patients
with peptic ulcer disease will have an antrum-predominant
H. pylori gastritis [23,24] , The biliary reflux creates a
microenvironment that is not suitable for H. pylori and it
will eradicate the microorganisms from the anastomosis
after surgery. The microscopy of the anastomosis will
therefore change from the chronic active H. pylori gastritis
picture into that of the typical reflux gastritis. The
most important features of reflux gastritis are foveolar
hyperplasia, congestion, paucity of inflammatory infiltrate,
reactive epithelial change and smooth muscle fiber
proliferation. These changes are already apparent shortly
after surgery; less so when a Roux-en-Y conversion is
carried out to avoid reflux [25,26] . The picture is therefore
directly related to the reflux of bile, as is the eradication
of H. pylori from the anastomosis.
In the long run, other microscopic features are encountered
in the operated stomach [27] . Loss of parietal
cells with the subsequent disappearance of the chief cells
introduces an accelerated mucosal atrophy that is caused
by the lack of the trophic hormone gastrin and the
vagotomy that is mostly done simultaneously. The specialized
glandular mucosa is replaced by intestinal metaplasia
and pseudopyloric metaplasia [28-31] . Atrophy of the
gastric mucosa may lead to vitamin B12 deficiency. At the
site of the anastomosis, the glands often become cystically
dilated, and sometimes these cystically dilated glands
herniate through the muscularis mucosae. This provides
a nodular aspect to the anastomosis and gives rise to a
microscopic picture known as gastritis polyposis cystica
or gastritis cystica profunda [32-34] . Erosions may occur as
a result of compromised vasculature due to the surgery,
but in the case of persistent ulceration after surgery,
Zollinger-Ellison-like syndrome or a retained antrum
needs consideration and these conditions are accompanied
by high gastrin levels. The retained antrum is caused
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by resection that is too limited and G-cell hyperplasia in
the stretch of antral mucosa left behind [35,36] .
Xanthelasmas, also known as gastric xanthomas or
gastric lipid islands, are aggregates of foamy macrophages
filled with lipids that can be seen in the stomach
and more often after partial gastrectomy [37,38] . At endoscopy,
they appear as grossly visible whitish nodules or
plaques, well circumscribed, with a size varying from 1
to 10 mm in diameter [39,40] . They typically occur along
the lesser curve [41] , the so-called “magenstrasse” where
generally reflux is most severe. It is felt that these aggregates
phagocytose remnants of cellular debris after degradation
due to chemical injury, and they are harmless.
Their importance lies in the fact that these should not be
confused with signet ring cell carcinoma, because the microscopy
of xanthelasma can resemble signet ring cells.
Special stains for mucin or immunohistochemistry for
cytokeratins versus histiocytic macrophages makes this
differentiation easy [42,43] . Xanthelasmas occur more frequently
in stomachs harboring other pathological changes
such as chronic gastritis, atrophic gastritis and intestinal
metaplasia [39,44] . The significance of these lesions remains
unknown.
PREMALIGNANT CONDITION
The stump of the stomach after remote gastric resection
because of benign ulcer disease is a well-defined premalignant
condition. Many studies in the past have confirmed
that, after remote partial gastrectomy, there is an
increased risk for stomach cancer [3,45-49] . GSC is defined
as a malignancy of the stomach occurring > 5 years after
initial partial gastrectomy, to confusion with cancer recurrence
after initial misdiagnosis. The risk for stump cancer
is remarkable because most of these patients suffer from
peptic ulcer disease prior to surgery. The relation between
peptic ulcer disease and gastric cancer is not fully
understood. Gastric cancer and peptic ulcer disease are
inversely associated and they are accompanied by distinct
patterns of acid secretion [50] ; by contrast, gastric ulcers,
non-peptic gastric ulcers, and gastric cancer partly share
pathophysiological features [51-53] . The part of the stomach
that is at the highest risk for gastric cancer is removed by
surgery. Nevertheless, with an increasing postoperative
interval, there is a steadily increasing risk for stomach
cancer in the gastric remnant. After more than 15-20
years postoperatively, the risk is higher than can be expected
for an age- and sex-matched general population,
and it rapidly increases thereafter [45,48,54] . In line with the
increased risk for stomach cancer, the post-gastrectomy
stomach also harbors dysplasia relatively frequently [29,55,56] .
The dysplasia is typically encountered around the gastric
anastomosis, and similarly the cancers are almost exclusively
found there. Both the dysplasia and the cancers can
be multifocal and extensive mapping of the mucosa with
endoscopic biopsies is warranted. Unlike primary gastric
cancer, which is frequently resectable (resectability rate in
Poland: 66%), gastric stump carcinoma once detected be-
3202 July 7, 2012|Volume 18|Issue 25|