allied
academies
Page 46
Journal of Gastronenterology and Digestive Diseases
|
Volume 3
J u n e 2 5 - 2 6 , 2 0 1 8 | D u b l i n , I r e l a n d
GASTROENTEROLOGY
International Conference on
Domenico Macaluso is a surgeon and an en-
doscopist. He graduated in Palermo (Sicily) and
is responsible for Digestive Endoscopy of the
Hospital Presidium of Ribera (Agrigento). He
also has a qualification of Rescue Diver and has
coordinated several underwater researches in
the Mediterranean, in the hypoxic basins of the
oceanic ditches. He compared the methano-
genic bacterial flora of the hypoxic marine ba-
sins, with the methanogenic bacteria of the in-
testinal microbiota and he collaborates with the
Department of Biotechnology of he University of
Siena, on the study of the probable capacity of
colon adenomas, to propagate at a distance, a
phenomenon that is probably mediated by the
physiological intraluminal hypoxic environment
of the colon.”
mimmomac57@gmail.comBIOGRAPHY
hypoxia, with an adaptation of their energy cycle. The colon mucosa is
an anoxic environment, where a lot of different microaerophilic bacteria
and archaebacteria live. This could be a crucial step in the survival of that
colonic neoplastic embolus, survival and adaptation being permitted by
that anoxic environment. A key role should be played by the mitochondrial
protein TRAP-1, with its ability to intervene on the transcription factor
HIF-1 levels. In normoxic conditions, this mediator is degraded by
hydroxylation, whereas in neoplastic tissues TRAP-1 stabilizes HIF-
1. In effect, immune histochemical investigations have shown that in
malignant tumors there are significant high levels of HIF-1 in comparison
to healthy tissues and if a metastasic process is present, still higher HIF-1
levels are present. In this context, a kind of natural selection will favor the
growth of the cellular clone adapted to the hypoxic stress. We can recall
that HIF-1 is a potent stimulator mitogen, specific for endothelial cells;
it produces changes of cellular metabolism, triggering the activation
of glycolytic enzymes; leading angiogenesis and neovascularization,
through vascular endothelial growth factor activation. Significant should
be also the role of nitric oxide, involved in the tone regulation of the
newly formed vessels. If our finding will be confirmed in a high number
of patients, the current orientation to treat sessile adenomas of the colon
by means of endoscopic sub-mucosal dissection must be revised. There
is no doubt that early diagnosis of adenomatous polyps and their removal
by endoscopic resection reduces the incidence of the colon carcinoma,
but we must prevent the fragmentation of the polyp. Otherwise, the
resection of the tumor could produce the primummovens of an iatrogenic
spread of a colonic adenoma, due to the particular morphological
characteristics of the colonic mucosa (folds, diverticula) and the
presence of an anoxic environment. Even the slow intestinal transit, an
increasing condition for the actual lifestyle, could help the engraftment
of such adenomatous embolus. A dangerous situation for the patient,
being the adenoma a benign lesion that can evolve in a malignant lesion.
Moreover, it may be also true for a superficial colon cancer, if treated by
resection or endoscopic dissection: the residual fragments could be able
to colonize contiguous or distal areas resulting in repetitive carcinomas.
Experimental studies might confirm our hypothesis. One should be
carried out on cre-recombinase genetically modified mice, characterized
by a higher incidence of tumors in the distal colon. The experimental
procedure should be obtained by taking tumor fragments from a proximal
area of the colon and implant them by contact in the most distal areas,
and then analyze the survival, engraftment and development of the cell
aggregates. Another experimental procedure could be performed dosing
HIF-1 levels in humans, checking its values in comparison to the pO2
levels and dysplasia degree in different parts of the colon.”