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
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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
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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.
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Risk factors for gastric cancer
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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.
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Signs and symptoms of gastric cancer
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PainConstant 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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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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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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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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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.
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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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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.
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Risk factors for pancreatic cancer
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Signs and symptoms of pancreatic cancer
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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 
-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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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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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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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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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.
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Acknowledgments |
The light micrograph of gastric cancer
cells is reproduced with permission of Science Photo Library/Parviz M Pour.
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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.
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References |
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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 |
Edward E.
Rylander, M.D.
Diplomat American
Board of Family Practice.
Diplomat American
Board of Palliative Medicine.