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BMJ 2001;323:1413-1416 ( 15 December )
Clinical review
ABC of the upper gastrointestinal tract
Cancer of the stomach and pancreas
BMJ 2001;323:1413-1416 ( 15 December )
Matthew J Bowles, Irving S Benjamin.
Cancers of the stomach and the pancreas share similarly poor prognoses.
However, long term survival is possible if patients present at an early
stage. In England and Wales carcinoma of the stomach and pancreas cause
about 7% and 4% of all cancer deaths respectively. In women they are the
fourth and fifth most common causes of cancer death; in men their respective
rankings are third equal (with colonic cancer) and seventh.
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Endoscopic appearance of gastric carcinoma on the lesser curve of the
stomach
The incidence of distal gastric carcinoma has fallen in the West, probably
because of decreasing rates of infection with Helicobacter pylori, but it
remains one of the main causes of death from malignancy worldwide. The
incidence of proximal gastric cancer seems to be rising. These two gastric
cancers depend on the distribution and severity of H pylori gastritis, as
discussed in the earlier chapter on the pathophysiology of duodenal and
gastric ulcers and gastric cancer.1
Cancer of the stomach
Gastric adenocarcinoma is rare below the age of 40 years, and its incidence
peaks at about 60 years of age. Men are affected twice as often as women.
Chronic atrophic pangastritis associated with H pylori infection is one of
the most important risk factors for distal gastric cancer.
Risk factors for gastric cancer
* H pylori infection and atrophic gastritis
* Pernicious anaemia
* Adenomatous gastric polyps
* Partial gastrectomy
* Abnormalities in E-cadherin gene
* Family history of gastric cancer
Clinical presentation
Symptoms may not occur until local disease is advanced. Patients may have
symptoms and signs related to secondary spread (principally to the liver)
and to the general effects of advanced malignancy, such as weight loss,
anorexia, or nausea. Epigastric pain is present in about 80% of patients and
may be similar to that from a benign gastric ulcer. If caused by obstruction
of the gastric lumen, it is relieved by vomiting. Carcinoma of the gastric
cardia may cause dysphagia.
Signs and symptoms of gastric cancer
Symptoms
Signs
bullet Pain
bullet Cachexia, weight loss, anaemia
Epigastric
bullet Epigastric mass
Back (advanced)
bullet Hepatomegaly
bullet Anorexia
bullet Palpable left supraclavicular
bullet Vomiting
node (Troisier's sign)
bullet Dysphagia
bullet Iron deficiency anaemia
bullet Haematemesis or melaena
bullet Weight loss
Constant abdominal pain, and particularly back pain, are sinister symptoms
implying local invasion by tumour. Chronic or acute bleeding from the tumour
may occur, with consequent symptoms. There is often little to be found on
examination, but there may be a palpable epigastric mass. The classic
Troisier's sign (left supraclavicular lymph node enlargement) is rare.
Investigations and staging
Endoscopy and barium meal are the principal investigations. Endoscopy allows
direct visualisation and biopsy of the carcinoma. Differentiation between
benign and malignant gastric ulcers at endoscopy can be difficult, and
several biopsies are therefore taken (ideally six) from all parts of the
ulcer. Diagnostic accuracy approaches 100% if 10 samples are taken. A benign
gastric ulcer is probably not a premalignant condition.
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Barium meal showing large obstructing carcinoma of the body of the stomach
A barium study gives a better impression of the anatomy of the tumour and
the degree of obstruction. It is also helpful for diagnosis of linitis
plastica, which may be missed at gastroscopy. In the presence of dysphagia
it is important to request a barium swallow and meal rather than a barium
meal alone.
Endoscopy and barium studies are complementary. If the first investigation
is negative in a patient with sinister symptoms the other test is indicated.
If a diagnosis of benign ulceration is made it is essential to repeat the
endoscopy and biopsies after four to eight weeks of medical treatment to
confirm ulcer healing and the benign nature of the lesion.
Staging of the disease by computed tomography of the thorax and abdomen, and
sometimes by laparoscopy or endoscopic ultrasonography, is appropriate only
in those patients who are proceeding to surgery.
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Light micrograph of human stomach cancer. Most of the cells seen here are
cancerous, having large, irregular shapes and multiple nuclei
Differential diagnosis
Once a gastroscopy or barium study has been performed, there are usually few
problems with the diagnosis of gastric carcinoma. The difficulty lies in
deciding which patients need urgent investigation of their presenting
symptoms. A good initial symptomatic response to acid suppression does not
exclude malignancy. Guidelines from the British Society of Gastroenterology
for the investigation of dyspepsia suggest that all patients aged over 45
years should undergo endoscopy, whereas those under 45 need endoscopy only
if they have symptoms or signs that raise suspicion of malignancy.
Treatment
Curative treatment
The decision to perform a gastrectomy depends on the patient's general state
of health and nutrition and the preoperative staging of the cancer. If there
is no evidence of local invasion or of metastatic spread, resection is
offered as a potential cure. Overall perioperative mortality is about 2%.
Long term survival depends principally on the extent of lymph node
metastases.
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Total gastrectomy for treatment of gastric cancer (left) and subsequent
reconstruction by Roux-en-Y anastomosis (right)
Chemotherapy may have an increasingly important role to play in treating
gastric carcinoma. Recent emphasis has been on preoperative chemotherapy in
order to "downstage" the tumour. There seems to be little place for
radiotherapy in the treatment of gastric carcinoma at present.
Palliative treatment
Patients with distal obstructing tumours may benefit from a subtotal
gastrectomy or gastrojejunostomy despite the presence of metastases.
Stenting of tumours of the gastric cardia relieves dysphagia. Other
treatments include endoscopic laser therapy for unresectable obstruction or
bleeding lesions. Blood transfusion may be appropriate for symptomatic
anaemia. The management of pain from gastric carcinoma follows established
palliative care practice. Coeliac plexus nerve blocks may be effective. As
with any malignant condition, the management of symptoms is
multidisciplinary and is often led by palliative care and hospice based
teams.
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Early gastric cancer. Top left: endoscopic appearance of cancer before dye
spraying. Top right: the same lesion after spraying with 0.2% indigo carmine
dye. Bottom left: lesion outlined by burn marks before excision. Bottom
right: mucosal defect after removal of the lesion with 1 cm margin (blue
colour is due to indigo carmine dye)
Prognosis
The disease is incurable in about half of patients at presentation. With
regional lymph node metastases, five year survival after gastrectomy is
about 10%. In those with only perigastric lymph node involvement survival
rises to 30%, and in those with gastric carcinoma confined to the stomach
five year survival is about 70%. Only 10% of patients with hepatic
metastases survive a year.
Early gastric cancer
Early gastric cancer is a carcinoma diagnosed before it has penetrated the
full thickness of the stomach wall or metastasised, but this accounts for
less than 5% of gastric carcinomata in the West. In Japan, where the
incidence of gastric carcinoma is much higher (about 10%), population
screening detects a far greater proportion of asymptomatic early gastric
cancer. With aggressive surgery, five year survival rates of 90% have been
reported from Japan. It is unclear, however, whether these differences in
survival are due to early detection, differences in the disease or its
pathological definition, or operative technique.
Cancer of the pancreas
The incidence of pancreatic cancer is about 10 per 100 000 population in
Western Europe. The incidence rises steadily with age, and the disease is
slightly more common in men than in women. Alcohol, chronic pancreatitis,
diabetes, and coffee do not predispose to pancreatic cancer.
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Computed tomogram showing dilated intrahepatic ducts caused by an
obstructing lesion of the lower end of the common bile duct
Pathological features
The commonest pancreatic neoplasm is ductal adenocarcinoma. Most cancers
arise in the head, neck, or uncinate process of the pancreas and may
compress the common bile duct. Less than a third occur in the body and tail
of the pancreas.
Periampullary malignancies may arise from the pancreas, the distal common
bile duct, the ampulla of Vater, or the duodenum. Pancreatic carcinoma
accounts for up to 90% of this group, but the rest are
important---periampullary tumours present early because they obstruct the
common bile duct and cause jaundice when they are small, so they have better
prognoses than pancreatic carcinoma.
Clinical presentation
The classic presentation is painless, progressive, obstructive jaundice.
Most patients also have epigastric discomfort or dull back pain. A large
carcinoma of the head of the pancreas may obstruct the gastric outlet.
Symptoms from a carcinoma of the body or tail of the pancreas are usually
more vague, and the tumour is often locally advanced by the time of
diagnosis.
Risk factors for pancreatic cancer
* Smoking
* Partial gastrectomy
* Dietary fat
* Family history of pancreatic cancer
Signs and symptoms of pancreatic cancer
Symptoms
Signs
bullet Obstructive jaundice---dark urine,
bullet Jaundice
pale stools, pruritus
bullet Cachexia, anaemia
bullet Pain
bullet Epigastric mass (late)
Back (common)
bullet Palpable gall bladder
Epigastric
(Courvoisier's sign)
bullet Vomiting
bullet Weight loss
bullet Anorexia
bullet Haematemesis or melaena (late)
Steatorrhoea may sometimes occur as a result of pancreatic duct obstruction
and may be difficult to differentiate from the pale stool of obstructive
jaundice. There are also the general effects of malignant disease.
The patient is usually jaundiced and may be anaemic or cachectic. There may
be an epigastric mass or an irregular, enlarged liver because of metastases.
Courvoisier's law states that, in the presence of jaundice, a palpable gall
bladder is unlikely to be due to gall stones. This is because stones usually
result in a fibrotic gall bladder, which will not distend in the presence of
obstruction of the common bile duct.
Investigations and staging
Serum biochemistry will confirm jaundice and also give some information
about its cause: alkaline phosphatase and gamma -glutamyltransferase tend to
be predominantly raised in obstructive jaundice. Disproportionate elevation
of the aminotransferases (transaminases) leads to suspicion of
hepatocellular involvement. Tumour markers may be of value in diagnosis:
carcinoembryonic antigen (the marker associated with colonic carcinoma) is
elevated in up to 85% of cases. Raised serum levels of CA 19.9 are
associated with carcinoma of the pancreas but also with obstruction of the
common bile duct from any cause. Lack of tumour markers should not delay
investigation of jaundiced patients; their main use is in monitoring
response to treatment and disease progression.
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Endoscopic retrograde cholangiopancreatography showing lower common bile
duct stricture (endoscope has been withdrawn)
Ultrasonography is the initial investigation for patients with jaundice. A
dilated common bile duct or intrahepatic ducts differentiate obstructive
(posthepatic) jaundice from prehepatic and hepatic jaundice. Liver
metastases are easily detected.
Endoscopic retrograde cholangiopancreatography visualises the common bile
and pancreatic duct, and carcinoma of the head of the pancreas produces a
characteristic malignant stricture of the lower end of the common bile duct.
Brushings can be taken for cytological analysis, and the stricture may be
dilated and stented to re-establish bile drainage into the duodenum. The
main complication is acute pancreatitis, especially if therapeutic
procedures are performed.
Computed tomography further assesses the primary tumour and detects lymph
node involvement and hepatic or pulmonary metastases. If a mass is seen a
fine needle aspirate can be taken under tomographic or ultrasound guidance
for cytology, which has a sensitivity (a positive result when tumour is
present) of about 70%. A core biopsy for histology can also be obtained.
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Fine needle aspiration of a pancreatic mass under computed tomographic
guidance
Differential diagnosis
Anicteric patients with pancreatic carcinoma are usually initially
investigated for their pain by gastroscopy or ultrasonography. Unless good
views of the pancreas are obtained by the latter, computed tomography is
required for the diagnosis.
Chronic pancreatitis may have a similar presentation, but there is usually a
history of alcohol misuse. However, the two conditions may be radiologically
indistinguishable, and fine needle aspiration cytology or histological
assessment is needed. For prognosis, it is important to distinguish
malignant periampullary lesions from tumours of the head of the pancreas.
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In Whipple's procedure for pancreatic cancer the head of the pancreas,
distal common bile duct, gall bladder, duodenum, and distal stomach are
excised (left). Reconstruction involves anastomosis of the pancreatic duct,
common hepatic duct, and distal stomach to a loop of jejunum (right)
Treatment
Surgery provides the only realistic hope of long term survival, but it is of
value only if the primary tumour is no more than a few centimetres in
diameter and is free of major blood vessels and if there is no metastatic
spread. Unfortunately, few patients meet these criteria.
Suitable patients undergo Whipple's procedure. The head of the pancreas, the
distal common bile duct, the gall bladder, and the duodenum and distal
stomach are excised. Reconstruction involves anastomosis of the pancreatic
duct, the common hepatic duct, and the distal stomach to a loop of jejunum.
Perioperative mortality is now less than 5% in experienced hands, and
complication rates have decreased, but Whipple's procedure remains a
formidable operation, and patients must be fit in order to be suitable. A
modification allows preservation of the distal stomach and pylorus, which
may have long term nutritional benefits.
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Radiogram of stent placed to relieve duodenal obstruction caused by
carcinoma of the pancreas
Distal pancreatectomy may be suitable for carcinoma of the body or tail, but
few patients are suitable. Total pancreatectomy and extended vascular
resections are rarely advocated.
Postoperative chemotherapy has been shown to be of some benefit after
pancreatic resection, and there is currently much interest in the role of
new chemotherapeutic agents in pancreatic cancer. Postoperative radiotherapy
has proved ineffective.
Palliative treatment
Jaundice is palliated by stenting the stricture at the lower end of the
common bile duct; this has superseded operative palliation. Some 15-20% of
patients develop duodenal obstruction, which can be relieved by laparoscopic
gastrojejunostomy. There is no indication for prophylactic
gastrojejunostomy, because most patients die of their disease before
duodenal obstruction becomes a problem.
Palliation of pain and of other symptoms is best managed by a hospice based
multidisciplinary palliative care team. Coeliac plexus block is often
extremely valuable.
Prognosis
The prognosis of unresectable pancreatic carcinoma is poor, with few
patients surviving longer than a year from diagnosis. Five year survival
after resection for pancreatic carcinoma has steadily improved and is now
10-20% in major centres. This rises to about 50% for resection of
periampullary tumours.
Acknowledgments
The light micrograph of gastric cancer cells is reproduced with permission
of Science Photo Library/Parviz M Pour.
Footnotes
Matthew J Bowles is consultant liver transplant and general surgeon, King's
College Hospital, London. Irving S Benjamin is professor of surgery,
academic department of surgery (Denmark Hill), Guy's, King's, and St
Thomas's School of Medicine, King's College, London.
The ABC of the upper gastrointestinal tract is edited by Robert Logan,
senior lecturer in the division of gastroenterology, University Hospital,
Nottingham, Adam Harris, consultant physician and gastroenterologist, Kent
and Sussex Hospital, Tunbridge Wells, J J Misiewicz, honorary consultant
physician and honorary joint director of the department of gastroenterology
and nutrition, Central Middlesex Hospital, London, and J H Baron, honorary
professorial lecturer at Mount Sinai School of Medicine, New York, USA, and
former consultant gastroenterologist, St Mary's Hospital, London.
References
1.
Calam J, Baron JH. ABC of the upper gastrointestinal tract: Pathophysiology
of duodenal and gastric ulcer and gastric cancer. BMJ 2001; 323: 980-982
[Full Text]
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.
Edward E. Rylander, M.D.
Diplomat American Board of Family Practice.
Diplomat American Board of Palliative Medicine.