Download tumours of the small intestine

TUMOURS OF THE SMALL INTESTINE
Compared with the large intestine, the small intestine is rarely the seat of a
neoplasm, and these become progressively less common from the duodenum to
the terminal ileum.
Benign
Adenomas, submucous lipomas and gastrointestinal stromal tumours
(GISTs) occur from time to time, and sometimes reveal themselves by causing an
intussusceptions and intestinal bleeding .
Peutz–Jeghers syndrome; This is an autosomal dominant disease:
This consists of:
• Intestinal hamartomatosis is a polyposis affecting the whole of the small bowel
and colon, where it is a cause of haemorrhage and often intussusception;
• Melanosis of the oral mucous membrane and the lips and sometimes present
on the digits and the perianal skin.
Long-term follow-up of patients with Peutz–Jeghers syndrome has shown
reduced survival secondary to complications of recurrent bowel cancer and the
development of a wide range of cancers.
These include colorectal, gastric, breast, cervical, ovarian, pancreatic and
testicular cancer. It is therefore important to keep these patients under
surveillance. This can be done by endoscopy or contrast examinations every 3
years to detect early gastrointestinal cancers. It is also important to make sure
that female patients attend cervical and breast screening programmes.
Treatment
As malignant change rarely occurs, resection is only necessary for serious bleeding
or intussusception. Large single polyps can be removed by enterotomy, or short
lengths of heavily involved intestine can be resected.
The incidence of further lesions developing problems in the future can be
reduced by thorough intraoperative examination at the time of the first
laparotomy.
Using on-table enteroscopy, polyps suitable for removal can be identified.
Those lesions within reach can be snared by colonoscopy.
Malignant
Lymphoma: Unless there are particular surgical complications, Lymphoma are
usually treated with chemotherapy.
There are three main types, as follows:
1 Western-type lymphoma. These are annular ulcerating lesions, which are
sometimes multiple. They are now thought to be non-Hodgkin’s B-cell lymphoma
in origin. They may present with obstruction and bleeding, perforation, anorexia
and weight loss.
2 Primary lymphoma associated with coeliac disease. There is an increased
incidence of lymphoma in patients with coeliac disease; this is now regarded as a
T-cell lymphoma.
Worsening of the patient’s diarrhoea, with pyrexia of unknown origin together
with local obstructive symptoms, are the usual features.
3 Mediterranean lymphoma. This is found mostly in North Africa and the Middle
East and is associated with α-chain disease.
Carcinoma can present with obstruction, bleeding or diarrhoea.
Complete resection offers the only hope of cure
Carcinoid tumour
These tumours occur throughout the gastrointestinal tract, most commonly in the
appendix, ileum and rectum in decreasing order of frequency. They arise from
neuroendocrine cells at the base of intestinal crypts. The primary is usually small
but, when they metastasise, the liver is usually involved, with numerous
secondaries, which are larger and more yellow than the primary; when this has
occurred, the carcinoid syndrome will become evident.
The tumours can produce a number of vasoactive peptides, most commonly 5hydroxytryptamine (serotonin), which may be present as 5-hydroxyindoleacetic
acid (5-HIAA) in the urine during attacks.
The clinical syndrome itself consists of reddish-blue cyanosis, flushing attacks,
diarrhoea, borborygmi, asthmatic attacks and, eventually, sometimes pulmonary
and tricuspid stenosis. Classically, the flushing attacks are induced by alcohol.
Treatment
Most patients with gastrointestinal carcinoids do not have carcinoid syndrome.
Surgical resection is usually sufficient.
In patients with metastatic disease, multiple enucleations of hepatic metastases
or even partial hepatectomy can be carried out.
Octreotide (a somatostatin analogue), reduces both flushing and diarrhoea, and
octreotide cover is usually used in patients with a carcinoid syndrome who have
surgery to prevent a carcinoid crisis.
Gastrointestinal stromal tumours; These tumours can be either benign
or malignant. Increased size is associated with malignant potential.
GIST is a type of sarcoma that develops from connective tissue cells.
It is found most commonly in the stomach but can be found in other sites of the
gut. It occurs most commonly in the 50- to 70-year age group.
Patients with neurofibromatosis have an increased risk of developing these types
of tumour.
Patients may be asymptomatic.
Other symptoms include lethargy, pain, nausea, haematemesis or melaena.
Treatment
Surgery is the most effective way of removing GISTs as they are radioresistant.
Glivec (imatinib) is a tyrosine kinase inhibitor that has been shown to be effective
in advanced cases.
TUMOURS OF THE LARGE INTESTINE
Benign
Polyps can occur singly, synchronously in small numbers or as part of a polyposis
syndrome:
Inflammatory; Inflammatory polyps.
Metaplastic; Metaplastic or hyperplastic polyps.
Harmartomatous; Peutz–Jeghers polyp ,Juvenile polyp.
Neoplastic;
Adenoma
– Tubular
– Tubulovillous
– Villous
Adenocarcinoma
Carcinoid tumour
Adenomatous polyps
Adenomatous polyps vary from a tubular adenoma rather like a raspberry on a
stalk, to the villous adenoma, a flat spreading lesion.
Villous tumours more usually give symptoms of diarrhoea, mucus discharge and
occasionally hypokalaemia.
The risk of malignancy developing in an adenoma increases with increasing size of
tumour; for example, in 1-cm-diameter tubular adenomas there is a 10% risk of
cancer, whereas with villous adenomas over 2 cm in diameter, there may be a
15% chance of carcinoma.
Adenomas larger than 5 mm in diameter are usually treated because of their
malignant potential.
Colonoscopic snare polypectomy or diathermy obliteration with hot biopsy
forceps can be used.
Huge villous adenomas of the rectum can be difficult to remove even with
techniques per anus, and occasionally proctectomy is required; the anal sphincter
can usually be preserved.
Familial adenomatous polyposis
FAP is clinically defined by the presence of more than 100 colorectal adenomas.
Over 80% of cases come from patients with a positive family history.
However, 20% arise as a result of new mutations in the adenomatous polyposis
coli gene (APC).
It is less common than hereditary non-polyposis colorectal cancer (HNPCC) and
accounts for less than 1% of colorectal cancer.
Although the large bowel is mainly affected, polyps can occur in the stomach,
duodenum and small intestine.
The risk of colorectal cancer is 100% in patients with FAP.
Males and females are equally affected.
FAP can be associated with benign mesodermal tumours such as desmoid
tumours and osteomas.
Epidermoid cysts can also occur (Gardner’s syndrome); desmoid tumours in the
abdomen invade locally to involve the intestinal mesentery and, although nonmetastasising, they can become unresectable.
Carcinoma of the large bowel occurs 10–20 years after the onset of the polyposis.
One or more cancers will already be present in two-thirds of those patients
presenting with symptoms.
Symptomatic patients; These are either patients in whom a new mutation has
occurred or those from an affected family who have not been screened.
They may have loose stools, lower abdominal pain, weight loss, diarrhoea and the
passage of blood and mucus.
Polyps are usually visible on sigmoidoscopy by the age of 15 years and will
almost always be visible by the age of 30 years as are shown on a double
contrast barium enema.
If in doubt, colonoscopy is performed with biopsies to establish the number
and histological type of polyps.
If over 100 adenomas are present, the diagnosis can be made confidently, but it is
important not to confuse this with non-neoplastic forms of polyposis.
Asymptomatic patients
Direct genetic testing will reveal mutations in 80% of cases.
In the presence of an identified mutation in a family with FAP, any resulting
negative tests for this can be interpreted to mean that these individuals do not
carry the mutation. They can therefore be withdrawn from surveillance
programmes and warned that they are at normal population ‘risk’ of developing
colorectal cancer.
In those families where a mutation cannot be identified, then surveillance is
recommended annually.
If there are no adenomas by the age of 30 years, FAP is unlikely.
If the diagnosis is made during adolescence, operation is usually deferred to the
age of 17 or 18 years or when symptoms or multiple polyps develop.
Screening policy
1 At-risk family members are offered genetic testing in their early teens.
2 At-risk members of the family should be examined at the age of 10–12 years,
repeated every year.
3 Most of those who are going to get polyps will have them at 20 years, and these
require operation.
4 If there are no polyps at 20 years, continue with 5-yearly examination until age
50 years; if there are still no polyps, there is probably no inherited gene.
Examination of blood relatives, including cousins, nephews and nieces, is
essential, and a family tree should be constructed and a register of affected
families maintained.
Treatment
Colectomy with ileorectal anastomosis has in the past been the usual
operation because it avoids an ileostomy in a young patient and the risks of pelvic
dissection to nerve function. The rectum is subsequently cleared of polyps by
snaring or fulguration. The patients are examined by flexible sigmoidoscopy at 6monthly intervals thereafter.
The risk of carcinoma in the rectal stump was 10% over a period of 30 years.
The alternative is a restorative proctocolectomy with an ileoanal
anastomosis; this has a higher complication rate than ileorectal anastomosis.
It is indicated in patients with serious rectal involvement with polyps, those who
are likely to be poor at attending for follow-up and those with an established
cancer of the rectum or sigmoid.
Postoperative surveillance; Because of the risk of further tumour formation,
follow-up is important and takes the form of rectal/pouch surveillance.
Gastroscopies are carried out to detect upper gastrointestinal tumours.
Hereditary non-polyposis colorectal cancer (Lynch’s syndrome)
This syndrome is characterised by increased risk of colorectal cancer and also
cancers of the endometrium, ovary, stomach and small intestines.
It is an autosomal dominant condition.
The lifetime risk of developing colorectal cancer is 80%, and the mean age of
diagnosis is 44 years. Most cancers develop in the proximal colon.
Females with HNPCC have a 30–50% lifetime risk of developing endometrial
cancer.
Diagnosis
HNPCC can be diagnosed by genetic testing or Amsterdam criteria II:
• Three or more family members with a HNPCC-related cancer, one of whom is a
first-degree relative of the other two;
• Two successive affected generations; one or more of the HNPCC-related cancers
diagnosed before the age of 50 years;
• Exclusion of FAP
Malignant
In the UK, colorectal cancer accounted for 16 000 deaths in 2003 according to
Cancer Research UK statistics.
Genetics
APC mutations occur in two-thirds of colonic adenomas and carcinomas and are
thought to present early in the carcinogenesis pathway.
K-RAS mutations result in activation of cell signalling pathways. They are more
common in larger lesions, thus implying that they are later events in the
mutagenesis pathway.
Other genes involved include p53.
No single mutation is a common theme for all colorectal cancer cases.
However, knowledge of certain mutations can be used to assess prognosis and
direct adjuvant therapy.
Aetiology
The hypothesis is that increased roughage is associated with reduced transit
times, and this in turn reduces the exposure of the mucosa to carcinogens.
There have also been studies linking increased dietary animal fat, smoking and
alcohol to colorectal cancer.
There is some evidence that links cholecystectomy, and therefore increased bile
acid secretion, to an increased risk of colorectal cancer.
Adenocarcinoma of the colon
It is likely that all carcinomas start as a benign adenoma, the so called ‘adenoma–
carcinoma sequence’.
The annular variety tends to give rise to obstructive symptoms, whereas the
others will present more commonly with bleeding. Tumours are more common in
the left colon and rectum.
The four common macroscopic varieties of carcinoma of the colon are:
(1) Annular; (2) tubular; (3) ulcer; (4) cauliflower.
The annular variety tends to give rise to obstructive symptoms, whereas the
others will present more commonly with bleeding.
Distribution of colorectal cancer by site??
The spread of carcinoma of the colon; generally this is a comparatively slowgrowing neoplasm.
Local spread; the tumour can spread in a longitudinal, transverse or radial
direction; it spreads round the intestinal wall and usually causes intestinal
obstruction before it invades adjacent structures.
The ulcerative type more commonly invades locally, and an internal fistula may
result, for example into the bladder.
There may also be a local perforation with an abscess or even an external faecal
fistula.
This type of radial spread to adjacent organs has the largest impact on prognosis.
Lymphatic spread; Lymph nodes draining the colon are grouped as follows:
N1: nodes in the immediate vicinity of the bowel wall;
N2: nodes arranged along the ileocolic, right colic, midcolic, left colic and sigmoid
arteries;
N3: the apical nodes around the superior and inferior mesenteric vessels where
they arise from the abdominal aorta.
Bloodstream spread; This accounts for a large proportion (30–40%) of late
deaths. Metastases are carried to the liver via the portal system, sometimes at an
early stage before clinical or operative evidence is detected (occult hepatic
metastases).
Transcoelomic spread; Rarely, colorectal cancer can spread by way of cells
dislodging from the serosa of the bowel or via the subperitoneal lymphatics to
other structures within the peritoneal cavity.