Câncer gástrico
Embriologia
O canal alimentar primitivo é formado, numa fase inicial, pelo enclusuramento dentro do
embrião de uma porção da vesícula blastodérmica, e consiste de 3 partes:
a) the fore-gut within the cephalic flexure and dorsal to the heart;
b) the mid-gut, opening into the yolk-sac;
c) the hind-gut, within the caudal flexure.
From the fore-gut are developed the pharynx, esophagus, stomach and duodenum,
and further, as diverticula from the duodenum, the liver and pancreas.
Soon a fusiform dilatation, the future stomach, makes its appearance. From the
stomach to the rectum the alimentary canal is attached to the notochord by a band of
mesoblast, from which the common mesentery of the gut is subsequently developed.
The stomach undergoes a further dilatation, and its 2 curvatures can be recognized;
the greater directs towards the vertebral column and the lesser towards the anterior wall
of the abdomen, while of its 2 surfaces one looks to the right and the other to the left.
Changes also take place in the position and direction of the stomach; it falls over
on to its right surface, which henceforth is directed backwards, while its original
left surface looks forwards; further its greater curvature is drawn downwards and to
the left away from the vertebral column, while its lesser curvature is directed
upwards, and the commencement of the duodenum is pushed over to the right side of
the middle line.
The bursa omentalis, which at first reaches only as far as the greater
curvature, grows downwards to form the great omentum, and this downward extension lies
in front of the transverse colon and the coils of the small intestine.
The small omentum is formed by a thinning of the mesoblast, which attaches
the lesser curvature to the anterior abdominal wall. By the subsequent growth of
the liver this leaf of mesoblast is divided into 2 parts: the small omentum between
the stomach and liver, and the falciform ligament between the liver and the abdominal
wall and diaphragm.
Anatomy
The stomach is the principal organ of digestion. It has 2 surfaces:
a) anterior: it's in relation with the diaphragm, the thoracic wall formed
by the anterior parts of the 7th, 8th and 9th ribs of the left side, the left lobe
of the liver and the anterior abdominal wall;
b) posterior: it's in relation with the diaphragm, the gastric surface of
the spleen, the left supra-renal capsule, the upper part of the left kidney, the anterior
surface of the pancreas, the splenic flexure of the colon, and the ascending layer
of the transverse mesocolon.
Almost the whole of this surface is covered with peritoneum, but behind the cardiac
orifice there is a small portion of the stomach which is uncovered, and is in
contact with the diaphragm and the upper portion of the left supra-renal capsule.
The lesser curvature extends between the cardiac and pyloric orifices along the
right border of the organ. It gives attachment to the 2 layers of the gastro-hepatic
omentum, between which blood-vessels and lymphatics pass to reach the organ.
The greater curvature is directed to the left.
The cardiac orifice is the opening by which the esophagus communicates with the
stomach. It's the most fixed part of the organ.
The pyloric orifice communicates with the duodenum, the aperture being guarded
by a valve. Its position varies with the movements of the stomach.
Near the pylorus the stomach exhibits a slight dilatation, the antrum.
Structure: the wall of the stomach consists of 4 coats:
1) the serous is derived from the peritoneum, and covers the entire surface of the
organ, excepting at the points of attachment of the greater and lesser omenta.
2) the muscular is situated immediately beneath the serous, and it consists
of 3 sets of fibers:
2.a) the longitudinal are most superficial; they're continuous with the
longitudinal fibers of the esophagus, radiating in a stellate manner from the cardiac
orifice;
2.b) the circular form a uniform layer over the whole extent of the stomach beneath
the longitudinal one; at the pylorus they're most abundant. They are continuous with
the circular ones of the esophagus;
2.c) the oblique fibers are limited chiefly to the cardiac region.
3) the submucous consists of a loose, filamentous, areolar tissue, connecting the
mucous and muscular layers.
4) the mucous has the surface smooth, soft and velvety, and is covered by a
single layer of columnar epithelium, which commences very abruptly at the cardiac
orifice, where the cells suddenly change from the stratified epithelium of the esophagus.
Between the mucous and submucous coats, is a thin stratum of involuntary muscular
fiber (muscularis mucosae), which in some parts consists only of a single
longitudinal layer.
Vessels and nerves:
Arteries: the gastric, the pyloric and right gastro-epiploic branches of the
hepatic, the left gastro-epiploic and vasa brevia from the splenic.
They supply the muscular coat, ramify in the submucous one, and are finally
distributed to the mucous membrane, where the arteries break up at the base of the
gastric tubules into a plexus of fine capillaries, anastomosing with each other,
and ending in a plexus of larger capillaries, which surround the mouths of the tubes,
and also form hexagonal meshes around the alveoli.
From these latter the veins arise and pursue a straight course downwards, to
the submucous tissue; they terminate either in the splenic and superior mesenteric
veins, or directly in the portal vein.
The lymphatics are numerous; they consist of a superficial and deep set, which
pass through the lymphatic glands found along the 2 curvatures of the organ.
The nerves are the terminal branches of the right and left pneumogastric, the
former being distributed upon the back, and the latter upon the front part.
A great number of branches from the sympathetic also supply the organ.
Gastric Cancer
The disease has its peak in the 7th decade, and it is twice as common in men
as in women.
Pathology
More than 90% are adenocarcinomas, and the remainder non-Hodgkin's lymphomas
or leiomyosarcomas. Differentiation between adenocarcinoma and lymphoma is critical,
since the prognosis and treatment for these 2 cancers differ considerably.
They can be subdivided into 2 categories: an intestinal type with cohesive neoplastic
cells forming glandlike tubular structures, and a diffuse type in which cell cohesion
is absent, so that individual cells infiltrate and thicken the stomach wall without
forming a discrete mass.
Intestinal-type lesions are frequently ulcerative, occur in the distal stomach more
often than the diffuse one, and are often preceded by a prolonged precancer phase.
Diffuse cancer occurs more often in young patients, develop throughout the stomach
but specially in the cardia, and are associated with a worse prognosis.
Early gastric cancer: it refers to a gastric cancer that penetrates no
deeper than the mucosa or submucosa regardless of the presence or absence of lymph
node metastases.
It's classified into 3 types:
I) the protruded type, presents as a nodular or papillary growth;
IIa) appears as a flat elevation that slightly thickens the mucosa two fold or more;
IIb) appears as a flat lesion at the level of the nonneoplastic mucosa;
IIc) presents as flat, superficial and slightly depressed;
III) is characterized by ulcer-like excavations that may be mistaken for benign ulcers.
Precursor conditions
Chronic atrophic gastritis and its associated abnormality, intestinal metaplasia,
are the lesions most closely linked. Atrophic gastritis usually begins as a multifocal
process in the distal stomach. As foci coalesce, a state of reduced gastric acid
production results, which may progress to metaplasia, dysplasia, and ultimately cancer.
Pathological studies indicate that intestinal metaplasia frequently accompanies
intestinal-type gastric cancer. But neither atrophic gastritis nor achlorhydria alone
is sufficient to cause gastric cancer.
Also pernicious anemia is associated with a 2 to 3 times excess risk of gastric
cancer, which may be the result of prolonged acid suppression, hypergastrinemia, and
neuroendocrine hyperplasia.
Also, H. pylori, but gastric cancer develops in only a small proportion
of infected persons, again suggesting that genetic or environmental cofactors are
required.
And among patients with adenomatous polyps of the stomach; it is directly
related to the size of the polyp and the degree of dysplasia.
But the marked rise in the incidence of adenocarcinoma of the gastric cardia and
distal esophagus appears to be correlated with an increase in the incidence of Barrette's
esophagus.
Patients with hereditary nonpolyposis colorectal cancer, an autosomal dominant
disorder with a high degree of penetrance, are at increased risk for gastric cancer,
and first-degree relatives of patients with gastric cancer have a 2 to 3 times increase
in the risk of contracting the disease.
Further support for a genetic influence comes from an increased risk of this cancer
among persons with blood type A, and the risk of cancer is inversely associated with
socioeconomic status, but the increasing incidence of adenocarcinoma of the distal
esophagus and gastric cardia is among higher socioeconomic classes.
Diets rich in fruits and vegetables are associated with a lower risk of cancer,
and diets rich in salted, smoked, or poorly preserved foods are associated with greater
risk. Consumption of highly salted and pickled foods over a long period may lead to
atrophic gastritis, making gastric mucosa more susceptible.
Anaerobic bacteria, which often colonize stomachs already affected by atrophic
gastritis and intestinal metaplasia, may convert nitrates and nitrites to potentially
carcinogenic nitrous compounds.
Refrigeration increases the availability of fruits and vegetables, obviates
the need for salting or similar methods of food preservation, and may prevent the
contamination of food by bacteria and fungi capable of activating various procarcinogens.
In summary, it appears that the intestinal type of gastric cancer is related
largely to environmental factors prevalent early in life.
In contrast, proximal, diffuse-type cancer, which is prevalent in both high
and low-risk regions of the world, may be associated with other factors that are still
unrecognized.
Patients with intestinal-type cancer have an increased frequency of overexpression
of epidermal growth-factor receptor, erb B-2 and erb B-3, and diffuse lesions have
been linked to abnormalities of fibroblast growth-factor systems.
Gastric surgery for benign conditions increases the risk of cancer by 2-6 times,
specifically when vagotomy is performed.
Diagnosis
Superficial and surgically curable cancers produces no symptoms, and as the
tumor becomes more extensive, an insidious upper abdominal discomfort may develop,
ranging from a vague sense of postprandial fullness to a severe, steady pain; anorexia,
with slight nausea, is common; weight loss also; vomiting occurs often when the tumor
invades the pylorus, and dysphagia is associated with a lesion of the cardia.
Hematemesis or melena (20%), although frank GI hemorrhage is uncommon and more
likely to be associated with leiomyoma and leiomyosarcoma.
The presence of a palpable abdominal mass generally indicates long-standing
growth and regional extension.
Gastric cancer spread by direct extension through the stomach wall to perigastric
tissue, adhering to or invading adjacent structures, such as the pancreas, colon or liver.
Direct extension into the colon may be associated with foul-smelling emesis or
the passage of recently ingested material in the stool.
The disease may also spread by lymphatic vessels to intra-abdominal lymph nodes
and supraclavicular nodes.
A tumor that spreads along the peritoneal surfaces may result in a periumbilical
nodule, an enlarged ovary, a mass in the cul-de-sac, or frank peritoneal carcinomatosis
and malignant ascites.
The liver is the most common site of hematogenous dissemination, although
pulmonary metastases are also seen.
There is anemia, hypoproteinemia, abnormal liver function and fecal occult blood.
Patients with gastric cancer infrequently present with various paraneoplastic
conditions, such as microangiopathic hemolytic anemia, membranous nephropathy, the sudden
appearance of seborrheic keratoses, filiform and papular pigmented lesions
in skin folds and mucous membranes (acanthosis nigricans), chronic intravascular
coagulation leading to arterial and venous thrombi.
Enema allows improved visualization of mucosal detail and may indicate diminished
distensibility of the stomach, which may be the only indication of a diffuse infiltrative
cancer; for lesions between 5 and 10 mm, false negative occurs (25%).
Differentiating a benign tumor from a malignant ulcer or even a lymphoma may be
impossible, and knowing the anatomical location of the ulcer isn't enough to predict
the presence or absence of a tumor.
Less than 3% of all gastric ulcers that are evaluated by endoscopy and biopsy
are malignant. Fiberoptic endoscopy and biopsy have a diagnostic accuracy of 95%, and
the accuracy increases with the number of biopsies. CT can delineate the extent
of the primary tumor, as well as the presence of nodal or distant metastases; comparisons
with the findings at laparotomy indicate that preoperative scans often underestimate
the extent of disease, principally because of radiographically undetectable metastases
to the lymph nodes, liver and omentum.
Preoperative ultrasonic endoscopy can determine the depth of tumor penetration and
the presence of nodal metastases, better than the CT.
Tumor markers haven't been useful in diagnosing this cancer at an early stage.
CEA has no role in the diagnosis, although it may be valuable in the PO follow-up.
Staging and prognosis
The pathological stage of gastric cancers remains the most important determinant of
the prognosis.
Beyond the stage, intestinal-type carcinoma has a greater rate of 5 years survival
than diffuse one (26% and 16%); also, poorly differentiated tumor, tumor with
abnormal DNA content, tumor size in excess of 10 cm, an adenosquamous histologic
type, and tumor with genetic alterations in proto-oncogenes have a diminished survival
rate.
The location of the primary tumor also predicts the outcome. The 5 years survival
after resection is 25% for distal tumors, 35% for middle third ones, 15% for proximal,
and less than 5% if the entire stomach is involved. The diminished survival in
proximal tumors may reflect the more aggressive, diffuse histologic features of
such lesions or the considerable technical difficulty of resecting them and
obtaining sufficiently wide radial margins.
TNM definitions:
Primary tumor (T):
TX - primary tumor can't be assessed;
T0 - no evidence of primary tumor;
Tis - carcinoma in situ: intraepithelial tumor without invasion of the lamina propria;
T1 - tumor invades lamina propria or submucosa;
T2 - tumor invades the muscularis propria or the subserosa;
T3 - tumor penetrates the serosa without invading adjacent structures;
T4 - tumor invades adjacent structures.
Nodal involvement (N):
The regional lymph nodes are the inferior gastric, splenic, superior gastric,
periesophageal, perigastric NOS, celiac and hepatic.
NX - regional lymph nodes can't be assessed;
N0 - no regional lymph node metastasis;
N1 - metastasis in perigastric lymph nodes within 3.0 cm of the edge of the primary tumor;
N2 - metastasis in the perigastric lymph nodes more than 3.0 cm from the edge of the
primary tumor or in lymph nodes along the left gastric, splenic, celiac, and common
hepatic arteries.
Distant metastasis (M):
MX - presence of distant metastasis can't be assessed;
M0 - no distant metastasis;
M1 - distant metastasis.
Stage 0: Tis, N0, M0;
stage IA: T1, N0, M0;
IB: T1, N1, M0 or
T2, N0, M0;
stage II: T1, N2, M0, or
T2, N1, M0, or
T3, N0, M0;
stage IIIA: T2, N2, M0 or
T3, N1, M0 or
T4, N0, M0;
IIIB: T3, N2, M0, or
T4, N1, M0;
stage IV: T4, N2, M0, or
any T, any N, M1.
Treatment
Complete surgical eradication of a gastric cancer, with resection of adjacent lymph
nodes, is the only chance for a cure.
Since resection of the primary lesion can also offer the most effective means
of symptomatic palliation, abdominal exploration with curative intent should be
undertaken, unless there is clear evidence of disseminated disease or other
contraindications to surgery.
In stage 0 more than 90% of patients treated by gastrectomy with lymphadenectomy
will survive beyond 5 years.
For distal tumor, partial gastrectomy with resection of adjacent lymph nodes
appears to be sufficient; there are greater rates of morbidity and mortality after total
gastrectomy, with no difference in overall survival.
For carcinomas in cardia, total gastrectomy may be necessary.
Survival correlate with tumor status at resection, as measured by local tumor
invasion or the status of lymph node metastasis.
The main drainage seems to occur over the pericardic region, either to nodes along
the lesser curvature and the left gastric artery and to nodes around the celiac axis,
pancreas, and splenic and common hepatic arteries or, less frequently, to nodes
along the greater curvature and splenic hilum and vessels; also the inferior paraesophageal
and diaphragmatic lymph nodes.
There appears to be a mutual relation among the status of lymph node metastasis,
tumor size and the depth of tumor invasion.
No lymph node metastases occur in patients with superficial carcinoma who has
mucosal invasion.
Most patients are heavy smokers and have advanced stage cancer and poor nutrition
before operation, what increase the pulmonary complications and decrease the immunity
and tissue healing ability.
We perform distal esophagectomy at the level of inferior pulmonary vein, or 8-10
cm from the upper margin of tumor, and confirm, grossly and microscopically, during
the operation that the cut end of the esophagus is free of tumor, and we have found no
tumor recurrence at the anastomotic site of esophagojejunostomy.
Extended radical resection diminishes the incidence of local recurrence, but probably
is insufficient to prevent distant metastasis, for patients with advanced stage carcinoma.
A variety of endoscopic methods are available for the palliation of symptoms
related to obstruction. The use of plastic and expansive metal stents have 80% of
success among selected patients with gastroesophageal tumor or tumor in the cardia.
Palliative resection, when possible, has been associated with a longer survival
and removes the risk of bleeding or obstruction.
Radiotherapy
Gastric cancer is resistant to radiotherapy, requiring doses of external-beam irradiation
that exceed the tolerance of surrounding structures, such as bowel mucosa and the
spinal cord.
Chemotherapy
A combination of fluorouracil, doxorubicin and mitomycin (or cisplatin) have 30% of
response, but just 6 to 10 months survival. All newly diagnosed patients with stage
III and IV should be considered candidates for clinical trials.