CARCINOMA OF STOMACH
Gastric cancer affects more than 22,000 Americans yearly. Cancer of the stomach is seen more than twice as often in men as in women. It is essentially a disease of middle and old age, about 85% of cases arising after the age of 40. Gastric cancer was previously the most common malignant neoplasm causing death in the male population, but today its incidence has slowly decreased, to between 16% and 25%. The increased incidences of lung carcinoma and esophageal cancer, primarily esophageal adenocarcinoma, have now caused these cancers to become the leading malignant causes of death in men. In women, cancers of the uterus and of the breast are more frequent than of the stomach.
The most
common type of gastric cancer is adeno- carcinoma, which arises from the glands
in the stomach lining. Other kinds of gastric cancer are lymphomas, GISTs, and
carcinoid tumors.
Gastric
cancer is a multifactorial disease and has several potential contributory
factors. H. pylori infection is a risk factor in 70% of gastric cancers
worldwide, but only 2% of people with the infection develop stomach cancer. The
mechanism by which H. pylori induces stomach cancer potentially involves
the action of H. pylori virulence factors such as CagA and chronic
inflammation. Smoking increases the risk of developing gastric cancer; in
smokers most tumors occur in the upper part of the stomach near the esophagus.
Some studies show increased risk with alcohol consumption. Dietary factors are
not proven causes, although nitrates and nitrites in cured meats can be
converted into com- pounds that have been found to cause stomach cancer in
animals. People may possess certain risk factors, such as those that are
physical or genetic, that can alter their susceptibility for gastric cancer.
Heredity may well play a part, because not too infrequently gastric cancer has
been observed for several generations in members of the same family. A genetic
risk factor for gastric cancer is a defect of the CDH1 gene known as hereditary
diffuse gastric cancer. Atrophic gastritis, though by no means invariably
leading to cancer, is considered by many a precancerous, or at least a
potentially precancerous, lesion. Transitional changes from an atrophic mucosa
to hyperplastic and papillomatous areas have been demonstrated. Chronic gastric
ulcers can rarely undergo malignant transformation. About 17% of all gastric
cancers arise in ulcers, and approximately 10% of benign nonhealing ulcers may
later become malignant. It is always a matter of primary concern for the physician
to exclude malignancy of a gastric ulcer with endoscopic evaluation and
biopsies, with follow-up to ensure complete healing of benign
gastric ulcers.
The
treatment of stomach cancer generally involves a team approach, with surgical,
medical, and radiation oncologists. Surgical resection with an adequate
lymphadenectomy is essential for a cure. Team members treat patients with
chemotherapy and radiation therapy before or following surgery; this has
recently been proven to improve the cure rate for this disease. Some patients
may undergo only chemotherapy before and after surgery.
Plate 4-60
NEAR CARDIA AND IN FUNDUS
CARCINOMA
NEAR THE CARDIA AND IN THE FUNDUS
Gastric
cancer may develop in any part of the stomach. From a clinical point of view,
by reason of the diagnostic, prognostic, and operative-technical aspects, it is
reasonable to differentiate two types of carcinoma in the upper portions of the
stomach, namely, those located in the cardia (which involves the
gastroesophageal junction) and those occupying the fundus.
The cardiac
carcinoma, even in its earlier stages, inter-feres with the free passage of
food, causing marked dysphagia. This fact often permits a relatively early
diagnosis. Thus, it is not surprising that the operative treatment of these
tumors yields probably the best long-term results of treatment of all
carcinomas of the stomach. In contrast, fundic carcinoma, like other
neoplasms in the so-called “silent” gastric zones, remains undiscovered usually
for a long time. It often infiltrates in the direction of the major curvature. Because the tumors have a
marked tendency to bleed once they have reached a certain size, severe chronic
anemia or a sudden hemorrhage may give the first late clue to their existence.
The cardiac
carcinoma often exceeds the bounds of the stomach, either by submucosal
infiltration or by more superficial extension, and narrows the cardiac orifice
or even the most distal portions of the esophagus. In such instances, it is
difficult to differentiate by x-ray or even endoscope a cardiac carcinoma from primary
cancer of the distal esophagus. This question may sometimes be decided by
endoscopic biopsies with evaluation by a pathologist. Otherwise, the x-ray
diagnosis of cancer in the upper part of the stomach is relatively easy,
particularly if the growth has altered the anatomic relation of stomach and
esophagus. If a stenosis is present, the adjacent portion of the esophagus will
be dilated and entry of the barium meal into the stomach will be delayed. When
doubts exist as to the diagnosis, the age of the patient, the past history, and
endoscopic results may help to exclude achalasia and other benign stenotic
lesions (esophagitis, peptic esophageal ulcer, strictures deriving from
corrosion). If passage through the cardia is not disturbed, the tumor may be overlooked,
particularly if one fails to examine the fundic region. Occasionally, a fundic
carcinoma may be flat and infiltration may have proceeded so superficially and
broadly that the gastric contour is altered very little.
Surgically,
the cardiac carcinoma is best approached by a left thoracotomy or
thoracoabdominal incision, because these approaches provide space for
additional resection of the esophagus if necessary. Tumors of the fundus,
located at a reasonable distance from the cardiac orifice, can be handled
through the abdominal approach, because a subdiaphragmatic transsection of the
esophagus seems to fulfill the requirements of a radical removal of the
neoplastic tissues. Should doubts arise during operation that the
subdiaphragmatic esophageal resection
is adequate, the field can be widened by prolonging the incision into the
thoracic wall and the diaphragm, or by continuing the operation by means of a
separate thoracotomy. The distal portion of the stomach should not be removed unless
absolutely necessary, because of the extension of the tumor. The physiologic
significance of preserving a segment of the stomach has been demonstrated
experimentally as well as clinically.
EARLY
CARCINOMA OF STOMACH
Some gastric
cancers start with a relatively sharply circumscribed area of infiltration,
spreading superficially on an
almost even level, without polypoid proliferation and showing little, if any,
ulceration. Of the numerous pathologic-anatomic forms in which carcinoma of the
stomach can make its appearance, this is the one that most often escapes early
clinical recognition, because it leaves the mucosal pattern and the contour of
the stomach unchanged for a long time, until the malignant growth has involved
a large area. In the early stages, this type expands only within the mucosal
layer; then it seizes
the submucosa and only much later encroaches upon the muscular coat. Its most
frequent location is the lesser curvature between the pylorus and the angular
incisure. Irregular flattening and breaks in the mucosal folds; distortion of
the rugae, particularly where they begin and end; more or less frank epithelial
defects; and, sometimes, small bleeding areas of erosion are the
macroscopically visible characteristics of this slow-growing tumor in its early
stages. As time passes, local inflammatory reactions and the extension of the
neoplasm in the muscularis takes place. On x-ray examination, first a scarcely
noticeable but then an increasingly striking stiffening of the region appears.
The normal peristaltic waves are interrupted in the rigid segment of the
gastric wall. A polygram of the peristaltic waves by repeated
roentgenographic views of several phases of a peristaltic movement may be
informative in these cases. In view of the fact that the contour of the organ
is not changed either by the formation of an ulcer crater or by endo- phytic
growth, only the most careful fluoroscopic examination of the condition of the
gastric wall or a series of spot films or a videofluoroscopy will permit one to
show this type of gastric carcinoma.
Plate 4-62
ADENOCARCINOMA OF STOMACH
From the
histopathologic point of view, the most frequent malignant growth in the
stomach is adenocarcinoma. Its macroscopic appearance, as the surgeon or the
pathologist sees it, depends essentially upon the time or the developmental
stage at which it happens to be recognized. It its early stages, it may be a
relatively small, cauliflowerlike mass only a few centimeters in diameter,
which projects into the lumen. Unfortunately, however, it reaches far larger
dimensions (though still being well circumscribed) before causing local
symptoms and before having metastasized to more distant structures. In any
event, the size of the tumor alone is not indicative of the spread to
neighboring organs. If it grows in the prepyloric area, as do about two thirds
of gastric cancers, it may bring about early signs of obstruction, gastric
enlargement, and disturbances of the motoric function of the stomach, which
lead to its discovery. Macroscopically visible invasion of the pylorus proper or of the
duodenum by a gastric adeno- carcinoma is an extreme rarity.
Gastric
adenocarcinoma usually arises from a broad base. Less frequently, a papillary
adenocarcinoma arises from a polyp or pedunculated adenoma and invades the
gastric wall through the stalk. Some adenocarcinomas assume on their surface a polypoid
or fungating appearance, with necrotic and ulcerating foci. On the
cut section, this “vegetative” type of carcinoma, as it has been called, presents a
yellowish, solid mass in a gray fibrillar stroma. The histologic architecture
of the adenocarcinoma may sometimes exhibit the typical columnar cell
arrangement, with formation of glandular spaces, but it is usually more
complicated and varies considerably. Atypical tubular glands may replace the
normal mucosal pattern, penetrating into the muscularis mucosae or spreading
from the submucosa as far as the serosal coat. The nuclei of the tumor cells
stain distinctly darker than
do those of the normal surrounding glands. At times, the tumor consists only of
closely grouped alveoli with cylindrical and cuboidal cells and hyperchromatic
nuclei. The cells lining these alveoli may, in some cases, contain substantial
amounts of mucus, and, occasionally, the entire tumor may be replaced by
gelatinous or slimy colloid material, in which only a few embedded
cancer cells may be found. In such instances, the displaced nuclei and
overextended, ruptured, or disintegrated cells in this mucinous matrix may
create a most complex histologic picture.
Linitis
plastica, also known as Brinton disease, scirrhous carcinoma, or leather bottle
stomach, is a morphologic variant of gastric cancer with a diffuse and
infiltrating form. This rare type of stomach cancer begins in the lining of the
stomach and spreads to the muscles of the stomach wall. This causes the wall to
become thick, hard, and rubbery, which leads to trouble in digesting food.
Another cause of linitis plastica is metastatic infiltration of the stomach,
particularly by breast or lung carcinoma.
Linitis
plastica produces a diffuse thickening of all layers and involves a large part
of the gastric wall (sometimes, the entire wall), which becomes contracted and
rigid. The scirrhous malignant lesion usually begins in the pyloric canal and
may, in some cases, remain limited to this region, where it may soon cause
signs of obstruction, because the profuse growth of its fibrotic components
markedly reduces the lumen. The same phenomenon takes place over the whole
gastric cavity, when the scirrhous growth has expanded extensively over the
entire lining. The mucosal folds become immobile and inflexible, while
simultaneously, as a result of the abundant formation of fibrous tissue, the
whole organ shrinks, assuming a shape that has been described as the leather
bottle stomach.
Histologically,
nests
of epithelial cells are scattered in dense fibrous tissue, which leaves nothing
of the normal gastric structures. The number of recognizable malignant cells is
gradually reduced, and, in the advanced stages, it is difficult to demonstrate
their presence except by the most painstaking microscopic study. In some cases
the fibrotic reaction has gone so far as to make recognition of the original nature of the process
practically impossible. In view of such proliferation of connective tissue, it
is not surprising that the primary cause was formerly considered to be a
chronic reactive inflammatory process and received, accordingly, the
designation linitis plastica.
The
roentgenographic appearance of linitis plastica, or scirrhous carcinoma, varies, of course, depending
upon the extent to which the gastric wall has become involved. If limited to
the pyloric region, a localized area of narrowing, distinct irregularities of
the contour, and the disappearance of the normal mucosal markings leave no
doubt as to the diagnosis. With the fibrotic process sufficiently advanced
at the pyloric canal to cause a more or less complete obstruction and the
more proximal parts of the wall still maintaining their normal structure and
extensibility, the stomach is markedly dilated and can retain food ingested
during the previous 24
hours or even over a longer period of time. If, however, the neoplasm has
spread over a larger segment or, as happens not infrequently, over the entire
inner aspect of the stomach, the cavity of the stomach presents itself as a
narrow tube with no mucous membrane pattern visible. The contour in such
cases may be erratically distorted, and the barium meal rushes through
the organ because of the rigidity of the pylorus, which, under these
circumstances, is permanently opened. Gastric peristalsis in these patients is
conspicuously absent. Because the obstruction in advanced linitis plastica is
located at the cardia, it is the esophagus that eventually becomes dilated.
With x-ray
findings as clear as those described above, the diagnosis of scirrhous
carcinoma presents no difficulties, and laboratory data, such as achlorhydria,
hypo- chromic or hyperchromic macrocytic anemia, or occult blood resulting from
the destruction of the glands or from erosions, provide little more than mere
additional supporting or confirming information. Upper endos- copy, at times
difficult to perform because of the rigidity and lack of air in the stomach,
may help establish the diagnosis, although the endoscopic picture of an
infiltrating carcinoma may now and then resemble that of a lymphoma or
hypertrophic gastritis, necessitating a biopsy for differentiation. The
unfortunate feature of the situation, however, is that these characteristic
x-ray pictures are seen only in a late stage of the disease when the presence
of lymph node metastases can be expected. Symptoms develop rather insidiously,
and patients come for medical care at a time when total gastrectomy, the only
sensible treatment for this condition, can scarcely be more than palliative.
The prognosis may become more favorable for the infiltrating type of carcinoma,
as for other types of cancer of the stomach, when the methods for early
recognition improve and when institutions such as cancer prevention clinics are
more widely used.
Plate 4-64
ULCERATING CARCINOMA
ULCERATING CARCINOMA OF STOMACH
Many
pathologists separate ulcerative cancer as a special type and consider it the
most common form of early detectable gastric carcinoma. Though all forms of cancer of the stomach
may become necrotic in parts and undergo ulcerative degeneration, it is particularly adenocarcinoma and
its papillary and polypoid varieties that tend to ulcerate while still
relatively small. Necroses and loss of substance on the surface of a diffuse,
infiltrating, scirrhous carcinoma are relatively rare and only superficial,
whereas the funguslike, proliferating, and more circumscribed (but still
broadly infiltrating) neoplasms tend often to become deeply ulcerated by the
sloughing of substantial parts of their central segments, probably because their blood supply cannot
keep pace with their rapid growth. In such cases, especially with the early
superficially spreading type, it may be extremely difficult, if not impossible,
to separate the ulcerating carcinoma diagnostically from a benign chronic,
callous, and penetrating peptic ulcer. The issue is further complicated by the
fact that a not negligible percentage of ulcers that we e originally benign may undergo malignant
alteration.
The functional
disturbances brought about by cancer of the stomach depend essentially on the
tumor’s location and size. The great majority of patients feel no discomfort or
pain in the early stages and report to their physician only when the neoplasm
has reached dimensions that cause obstruction of the pylorus or cardiac orifice
or reduction of the entire gastric lumen or secreting surface. At this time a
gamut of manifestations, from vague epigastric discomfort, nausea, and anorexia
to weight loss and cachexia, may be present, pointing to a serious digestive
dysfunction. If the tumor happens to invade the nerves, pain may become one of
the early or actually the earliest symptom. In such cases, as well as with
manifestations of an ulcerating tumor, the physician faces the most difficult
problem of differentiation between a cancer and a benign ulcer. In any event,
whatever the symptoms and whenever they appear, it has been estimated that at
least half of the patients with gastric carcinoma do not seek medical attention
until the tumor has extended beyond the stomach.
SPREAD OF CARCINOMA OF STOMACH
All types of
carcinoma of the stomach either spread by direct extension to neighboring
organs or metastasize by means of the lymphatics or bloodstream. Some types
have a greater tendency and some (e.g., scirrhous carcinoma) a lesser tendency
to produce metastases. The regional lymph nodes become involved, sometimes very
early and usually, though by no means always, in a definite sequence. With the
lesser curvature being, to a certain degree, the preferred site, the lymph
nodes of the upper left, anterior, and posterior walls of the stomach and their
drainage system along the left gastric artery and the coronary vein are those
first and most frequently affected. A rather serious prognostic significance
must be attached to an early involvement of the nodes in the pyloric area, including
the suprapancreatic nodes and those near the hilus of the liver, which excludes
any possibility of radical removal of the malignancy. Secondary growth of
malignant tumor cells in the lymph nodes of the prepyloric, pyloric,
and pancreatic regions and in the hepatoduodenal ligament may be
accompanied clinically by icterus, as a result of an obstruction of the common
bile duct, subsequent biliary stasis, and dilatation of the gallbladder (Courvoisier
law or sign). The liver is held as a site of predilection for metastases
of gastric cancer, either by direct spread or through the lymphatic routes
just mentioned. It is possible, but probably not common, for cancer cells to
enter the liver by way of the portal circulation. Similarly, though less
frequently, metastases develop in the lower part of the esophagus, colon,
pancreas, and gallbladder.
Metastatic
involvement of the lymph nodes along the greater curvature, in the gastrocolic
ligament, and in the omentum majus occurs less regularly than in those
structures along the lesser curvature. Occasionally, the cancer cells are
carried via celiac lymph nodes to the thoracic duct and the mediastinal and
supraclavicular lymph nodes (Virchow node).
Hematogenic
metastases in lung, bone, and brain (in that order of frequency) are relatively
rare and are encountered, of course,
only in far-advanced cases.
The direct
transplantation of aberrant cancer cells upon the peritoneum represents
a special type of spread. It requires complete penetration of the stomach wall
and, thus, is again a phenomenon of an advanced stage of gastric cancer. Once
the serosa has become involved, cancer cells may be set free and may settle on
the surface of any organ within the peritoneal cavity. The ovaries seem to be
the most frequent site, sometimes the only site of such implanted metastases,
which, in this organ, develop into
a histologically rather characteristic secondary neoplasm known as Krukenberg
tumor. If conditions permit, the simultaneous resection of the primary
tumor and the ovarian metastases seems justified and worth serious
consideration.
Another,
certainly not infrequent, site of metastases is the pelvic peritoneum, where
they may project into the rectum as a shelflike structure (rectal shelf of Blumer) and can be felt
on rectal examination.
