It is estimated that 2-3% of gastric cancers are of genetic origin so we know
today that a test would understand the predisposition to develop the disease, so
the relatives of those who rarely get sick must undergo this analysis. We know that
if there is a familiarity there could be some genetic alterations such as e-cadherin
(CDH1) that could greatly increase the risk of stomach cancer. But of course
it is currently unthinkable that the execution of genetic tests can become a standard
to always apply ".
Numerous studies confirm that this tumor is favored by the strong consumption
of foods conserved and rich in nitrates, from a poor diet of fruits and vegetables,
from the consumption of alcohol, from the habit of smoking and obesity. Among the
risk factors there is also infection not treated by Helicobacter pylori, a bacterium
primarily responsible for gastric ulcer.
And speaking of CDH1, a rare form of hereditary widespread gastric cancer has
been defined recently, linked to germinal mutations of this gene. "These mutations
confer an increased risk of developing not only widespread gastric carcinoma but
also, in women, lobular carcinoma of the breast. Germinal mutations of the CDH1
gene can be searched for through a genetic test (on blood or on tumor tissue) that
is performed after adequate genetic counseling. Identifying these mutations is of
fundamental importance, because it allows to put in place preventive measures aimed
at reducing the risk of neoplastic onset: healthy individuals with pathogenetic
mutations of the CDH1 gene are indeed candidates for a total prophylactic gastrectomy
".
The neoplastic process almost always originates from the mucosa, the innermost layer
of the gastric wall. In this case we speak of adenocarcinoma of the stomach, to
distinguish it from other tumors that more rarely can affect the organ and that
originate from the deeper layers of the wall (sarcomas and tumors of the gastrointestinal
stroma) or from the lymphatic system (primitive non-Hodgkin lymphoma of the gastrointestinal
tract).
They are those injuries that over time can evolve into overt cancer; those of
the stomach are:
- chronic A type gastritis (autoimmune, associated
with vitamin B12 deficiency and pernicious anemia) and B (or antral, may evolve
to carcinoma starting as atrophic process of the mucosa that then evolves into intestinal
metaplasia (the gastric epithelium becomes similar to that of the intestine) and
dysplasia)
- gastrorenection intervention (removal of part of the stomach) before the age of
40. After this surgery increases the risk of cancer in the stomach area remained
as it is exposed directly to the injurious action of pancreatic juices and bile.
In order to reduce this risk, this type of patient must be followed over time with
serious gastroscopies (every 5 years after 15 days of surgery), aimed at detecting
tumors in the initial stage and eradicating them.
- adenomatous gastric polyps
- Menetrier's disease
The stomach may also be affected by another form of tumor, the carcinoid tumor,
of a neuroendocrine nature.
Classification of Bormann, early gastric cancer
Type of stomach cancer, protundant, superficial elevation, flat, superficial depression and excavatum
According to the Bormann classification, gastric neoplasms divide, from the macroscopic
point of view, into: polypoid forms, ulcerated forms with detected edges, ulcerated
forms with indistinct edges and diffuse forms (plastic linite).
From the microscopic point of view we have seen the two forms, the intestinal type
and the diffused type.
The early gastric cancer is a tumor limited to the mucosa or submucosa and only
on the operative piece can the exact degree of tumor infiltration be established.
According to the Japanese AA, the EGC can be divided into:
- Type I- Vegetative polypoid lesion.
- Type II - Surface lesion detected (a), flat (b) or depressed (c).
- Type III - Excavation injury.
The improvement of endoscopy with the routine use of chromo-endoscopy and echoendoscopy techniques allowed to obtain much more reliable diagnostic results for the definition of superficial diffusion and parietal involvement of the neoplasm and for the diagnosis of multicentric forms. New endoscopic EGC resection techniques have been proposed as an alternative to gastric resection. It is possible to perform an endoscopic resection limited to the mucosa EMR (Endoscopic Mucosal Resection EMR) or including the submucosa (Endoscopic Submucosal Dissection ESD). Endoscopic resection is indicated in the presence of an intestinal EGC sec. the classification of Lauren, limited to the mucosa, well differentiated, of a diameter not exceeding 2 cm and without lymphatic or vascular invasion and / or intra-lesional ulcer. If an endoscopic R0 resection is confirmed at the final histological examination and the neoplasm has all the histological characteristics described, no further surgical treatments are necessary.
It is based on the appearance of the neoplasms and recognizes different classifications
according to the stage of the neoplasia.
In primordial stages, when it is confined to the mucosa and submucosa, the classification
is described in the following images, while in advanced neoplasms it is based on
the Borrmann classification, reported below.
The classification of the neoplasms mainly used, classifies the degree of infiltration
of the neoplasms according to the depth (T) based on the number of infiltrated lymph
nodes (N) and the presence of distant metastases (M).
The Japanese classification is different, based on the infiltration of the various
lymphatic stations present around the stomach.
Tis Limited to the mucosa without invasion of the basement membrane
T1a Limited to mucosa (invasion of the lamina propria)
T1b Invasion of the submucosa
T2a Invasion of one's own muscle
T2b Invasion of the sottosierosa
T3 Penetration of serosa without invasion of surrounding tissues
T4 Invasion of adjacent tissues / organs
Category N
N0 No lymph node involvement
N1 Interest of 1-6 lymph nodes
N2 Interest of 7-15 lymph nodes
N3 Interest of more than 15 lymph nodes
N ratio Ratio between the intruded / removed lymph nodes
Category M M0
Not metastasis at a distance
M1 Metastasis at a distance
Category R
R0 Not residual tumor
R1 Microscopic residue
R2 Macroscopic residue
95% of stomach tumors are epithelial and are called "adenocarcinoma". Gastric
adenocarcinoma develops from the cells that make up the inner lining of the stomach:
the gastric mucosa and can be distinguished in "proximal" or "distal". From the
histological point of view it is distinguished in "intestinal" or "diffused"; finally,
the tumor can be defined as "early" (initial) or "advanced" (advanced) based on
the stage of illness.
Intestinal stomach cancer is the most common and predominantly affects men over
50 years. It is associated with intestinal metaplasia, ie the transformation of
gastric epithelium into an epithelium similar to intestinal epithelium. These tumors
usually appear as formations facing the inside of the cavity and with expansive
growth.
Stomach cancer of diffuse type is slightly less frequent than the first and affects
indifferently men and women of average age over 45 years. In general, the neoplasia
arises from the normal gastric mucosa (which does not evolve towards the intestinal
type as happens in the other type) and, penetrating into the tissue, can give rise
to ulcers: in this case we talk about a stomach in a leather or linite bag plastic,
to underline how growth can lead to hardening of the organ walls. Characteristic
of this type of tumor is the presence of cells that under the microscope resemble
a ring with an embedded gem ("ring-shaped" cells).
Lymphomas
They are actually tumors of the immune system located in the stomach wall. About
4% of gastric cancers are non-Hodgkin's lymphomas. The therapy depends on the type
of lymphoma from which they originate.
Stromal gastrointestinal tumor (GIST, gastrointestinal stromal tumor). These are
rare tumors that originate in very early forms of cells of the stomach wall, called
Cajal interstitial cells. Some of these tumors are non-cancerous (benign).
Carcinoid tumor. They are about 3% of gastric cancers and originate from endocrine
cells of the stomach. More frequently they are tumors with indolent characteristics
and rarely give rise to metastatic localizations.
Krukemberg tumor. Tumor localized to the ovaries but due to the presence of neoplastic
cells that have migrated from the stomach to the ovary through the peritoneal cavity.
Altri tumori di origine gastrica molto rari: carcinoma a cellule squamose, carcinoma
a piccole cellule e leiomiosarcoma.
The therapeutic choices in gastric cancer are based on the stage of the disease
and so some Early stage lesions are currently treated definitively by endoscopic
mucosal resection, while other very advanced lesions require a prior chemotherapy
treatment to achieve better results.
Limited Resections (Endoscopic Mucosal Resection or EMR)
For a small percentage of early-stage lesions (Early) the endoscopic tumor resection
is currently available, but if the lesion is confined to the stomach mucosa, ie
it is of surface, does not sink, so to speak, "the roots" in the layer muscle and
does not affect the lymph nodes. Only then is the endoscopic treatment considered
therapeutic.
In most cases, however, it is essential to operate the:
Subtotal gastrectomy, if only the antrum is affected and the resection can be enlarged
to 2.5;
Total gastrectomy, if the lesion is extended and it is not possible to discern its
site with precision, if for example it affects the gastric bottom;
Enlarged gastrectomy of nearby organs and lymph nodes, which is perhaps more common.
Gastroenteroanastomosis, if the cardias is involved.
The lymph nodes must always be reclaimed up to the second level and the following
chemotherapy can significantly improve the prognosis.
Treatment with chemotherapeutic drugs - taken by mouth or injected intravenously
- aims to selectively kill cancer cells. In the case of stomach cancer, chemotherapy
may precede surgery (neoadjuvant chemotherapy) or be given after surgery (adjuvant
chemotherapy).
Various drugs and various therapeutic protocols are currently available, but among
the most used drugs are 5-fluorouracil, epirubicin and platinum. Chemotherapy can
generate side effects: including nausea, vomiting, hair loss and appetite
Various schemes are available to treat patients with advanced gastric cancer;
one must choose the most suitable one by assessing the patient's age and performance
status as well as the toxicological profiles of the individual drugs. The most used
schemes are:
FAM (5-fluorouracil + doxorubicin + mitomycin c)
FAP (as before but with cisplatin instead of mitomycin)
ECF
ELF (etoposide + 5-fluorouracil + levocorin) all bolus or continuous, with possible
addition of folinic acid
PELF (as before with further addition of cisplatin)
FAMTX (5-fluorouracil + doxorubicin + methotrexate)
FUP (5-fluorouracil + cisplatin)
Radiotherapy involves the use of high-energy radiation to destroy cancer cells.
Also this, like chemotherapy, can be prescribed before surgery (neoadjuvant radiotherapy)
to reduce the size of the tumor or after (adjuvant treatment).
In recent years, so-called "biological drugs" have also been developed in the
treatment of stomach cancer. Monoclonal antibodies are able to hit a specific target
of the tumor cell and determine its death.
In the case of gastric cancer, trastuzumab, associated with classical chemotherapy,
is used in patients who show a positivity to HER2 oncogene. The choice of this treatment
is taken only after having ascertained in the laboratory the presence of the specific
protein on the tumor cells.