Pancreatitis
Pancreatitis is primarily due to the intracellular activation of
trypsinogen to trypsin by numerous stimuli which, as yet, have not been fully
elucidated. The recent discovery that hereditary pancreatitis is related to an
abnormal cationic trypsinogen due to an abnormality in the long arm of
chromosome 7, in which histidine replaces arginine allowing in certain instances
intracellular activation of trypsinogen to trypsin, elucidates in
a small way intracellular mechanisms which can occur to cause this disease. In
hereditary pancreatitis the same defect can give rise both to acute and to
chronic pancreatitis. It is probable that acute pancreatitis is but a phase of
chronic pancreatitis; the two are inter-related. For clinical purposes it is
useful to divide pancreatitis into acute, which presents as an emergency, and
chronic which is a prolonged and frequently life-long disorder resulting from
the development of fibrosis within the pancreas.
Acute
pancreatitis is
defined as an acute condition presenting with abdominal pain and usually
associated with raised pancreatic enzyme levels in the blood or urine as a
result of inflammatory disease of the pancreas. Acute pancreatitis may recur.
Chronic
pancreatitis is
defined as a continuing inflammatory disease of the pancreas characterised by
irreversible morphological change typically causing pain and/or permanent loss
of function. Many patients with chronic pancreatitis have exacerbations, but the
condition may be completely painless.
Acute
pancreatitis
Incidence
Acute pancreatitis accounts for 3 per cent of all cases of abdominal
pain admitted to hospital in the UK. The incidence varies from 21 to 283 cases
per million population. In Japan the best estimate is that of 121 cases per
million population. The disease may occur at any age, with a peak in the young
male and the older female. The mortality has remained unaltered at 10—15 per
cent over the past 20 years. About one-third of patients die in the early phase
of an attack from multiple organ failure, while deaths occurring after the first
week of onset are due to infective complications. Eighty per cent of patients
will have a mild attack of pancreatitis in which the mortality is around 1 per
cent, while in those who have a severe attack of pancreatitis the mortality
varies from 20 to 50 per cent.
Aetiology
The two major causes of acute pancreatitis are biliary calculi, which
occurs in 5 0—70 per cent of
patients, and alcohol, which occurs in 25 per cent. The remaining cases may be
due to rare causes or be idiopathic (Table 55.4).
The importance of aetiology is that removal of
the causative factor can avoid further episodes of pancreatitis. Thus, in a
patient who has gallstone pancreatitis, the gallstones should be removed as soon
as the patient is fit to undergo surgery and, preferably, before discharge from
hospital.
Clinical
presentation
There are no pathognomonic symptoms and signs, but pain is usually the
cardinal symptom. It characteristically develops quickly, reaching maximum
intensity within minutes rather than hours, and persists for hours or even days.
The pain is
Acute pancreatitis should be suspected in the
patient who:
• develops marked abdominal pain, fever or unexplained shock
following abdominal surgery;
• presents with diabetic coma and shock;
• has clinical features suggesting myocardial infarction with abdominal
distension.
Nausea, vomiting and retching are usually
marked accompaniments. Vomiting is often frequent and persistent, and retching
may persist despite the stomach being kept empty by nasogastric aspiration.
Hiccoughs can be troublesome and may be due to gastric distension or irritation
of the diaphragm.
On examination the appearance may be that of a
patient who is well or, at the other extreme, one who is gravely ill with
profound shock, toxicity and confusion. Tachypnoea is common, tachycardia is
usual and hypotension may be present. The body temperature is often normal or
even subnormal, but frequently rises as inflammation develops. Mild icterus
can be caused by biliary obstruction in gallstone pancreatitis, and an acute
swinging pyrexia suggests cholangitis. Bleeding into the fascial planes can
produce blueish discoloration of the flanks (Grey Turner sign) or umbilicus
(Cullen’s sign). Neither sign is pathognomonic of acute pancreatitis; in
fact Cullen’s sign was first described with rupture of an ectopic pregnancy.
Subcutaneous fat necrosis may produce small red tender nodules on the skin of
the legs. Abdominal examination may reveal distension due to ileus or, more
rarely, ascites with shifting dullness. A mass can develop in the epigastrium
due to inflammation. There is usually muscle guarding in the upper abdomen,
although marked rigidity is unusual. A pleural effusion is present in
Investigations
A serum amylase four times above normal is indicative of the disease.
Plain abdominal X-ray findings include a generalised or local ileus (sentinel
loop), a colon ‘cut-off’ sign and a renal ‘halo’ sign. Occasional
helpful, but nondiagnostic, signs include calcified gallstones and pancreatic
calcification. A chest X-ray may show a spectrum of changes depending on the
disease severity. A pleural effusion is present in 20 per cent, and in severe
cases a diffuse alveolar interstitial shadowing may suggest an acute respiratory
distress syndrome.
Ultrasound scanning. The swollen pancreas may
be detected but the gland is poorly visualised in 25—50 per cent of cases.
Ultrasound is valuable in detecting free peritoneal fluid, gallstones,
dilatation of the common bile duct and, occasionally, other pathologies such as
abdominal aortic aneurysm.
If doubt remains a CT scan should be performed
in order to determine the diagnosis.
Laparotomy. To misdiagnose acute pancreatitis
is not uncommon because the presentation is so variable that even the shrewdest
clinician can be mistaken. The appearances at laparotomy are characteristic (Fig.
55.26).
Management
On account of the difference in outcome between patients with mild and
severe disease it is important to define that group of patients who will develop
severe pancreatitis. Various scoring systems have been introduced such as the
Ranson and Glasgow scoring systems (Table 55.5). A C-reactive protein level greater than 210 mg/litre in the
first 4 days of the attack or 120 mg/litre at the end of the first week has a
predictive performance similar to that of the other criteria and has the added
benefit of simplicity. Similarly, the Apache II scoring system, well used in
intensive care units, can be applied; a score of 9 or more indicates a severe
attack but excludes many with a lower score who will develop complications. An
Apache score of 6 or more will include 95 per
cent of all those who develop a complication.
If after initial assessment a patient is
considered to have a mild attack of pancreatitis, a conservative approach is
indicated with nil by mouth, intravenous fluid administration and frequent,
but noninvasive, observation. However, if the patient develops a severe attack
of pancreatitis then a more aggressive approach is required with the patient
being admitted to a high-dependency or an intensive care unit. The patient is
monitored invasively to ensure homeostasis of the cardiovascular, respiratory
and renal systems. In the mild attack antibiotics are not indicated unless there
is evidence of infection. There is no indication for pharmacological or
therapeutic treatments, and CT scanning is unnecessary unless there is evidence
of deterioration. The management of
General. Pancreatitis may involve all organs of the body (Tables 55.6
and 55.7) and present demands on the surgeon beyond his or her skills.
Those patients who develop systemic complications should be managed by a
multidisciplinary team. There is no role for surgery during the initial period
of resuscitation and stabilisation. The full care associated with critical care
medicine is applied to these patients, and surgical intervention is only
contemplated in the patient who deteriorates following successful stabilisation.
Once the presence of infected necrosis is suspected and confirmed, an
appropriate débridernent may be performed.. The only other indication for
intervention is the presence of cholangitis, in which case an endoscopic
sphincterotomy should be performed.
Local. Once the acute phase has been survived,
usually by the end of the first week, and major organ failure is under control,
then local complications become pre-eminent in the management of these patients.
An awareness of these complications is aided by carefully following the course
of the patient, and if clinical resolution does not take place a CT scan should
be performed to enable definition of any abnormality present. Such abnormalities
should he re-imaged at intervals until there is clear evidence of regression. If
a fluid collection or abscess persists then drainage, preferably under
radiological control, is indicated.
Definitions
Acute fluid collection. This occurs early in the course of acute
pancreatitis and is located in or near the pancreas. The wall encompassing the
collection is ill defined.
Acute pseudocyst. A collection of pancreatic
juice enclosed in a wall of fibrous or granulation tissue that arises following an attack of acute pancreatitis. Formation of a pseudocyst requires 4
weeks or more from the onset of acute pancreatitis (Figs 55.27 and
55.28).
Pancreatic necrosis. A diffuse or focal area
of nonviable parenchyma which is typically associated with peri pancreatic fat
necrosis. The onset of infection results in infected necrosis which is
associated with a trebling of the mortality rate.
Pancreatic abscess. A circumscribed
intra-abdominal collection of pus, usually in proximity to the pancreas
containing little or no pancreatic necrosis.
Pancreatic effusion. An encapsulated
collection of fluid arising as a consequence of acute pancreatitis, typically in
the pleural cavity.
Pancreatic ascites. Chronic generalised
peritoneal enzyme-rich effusion usually associated with pancreatic duct
disruption.
Pseudoaneurysm. Pseudoaneurysm is a false
aneurysm of a major peripancreatic vessel confined as a clot by the surrounding
tissues and often associated with infection. Recurrent bleeding is common, often
culminating in fatal haemorrhage.
Management
of local complications
Complications in pancreatic disease are serious and carry a significant
mortality. The prime role in the management of acute pancreatitis is that of the
conservative approach. If fluid collections cause symptoms or impair function
then percutaneous or transgastric drainage is appropriate. Sterile necrotic
material should not be drained. The only indication for
operative intervention in acute pancreatitis is the presence of an
abscess related to necrosis in or around the pancreas. All other complications
can be managed conservatively and, indeed, some authorities suggest that even an
infected necrotic pancreas can be managed conservatively with radiological
drainage. To determine whether a collection of peripancreatic oedema and fluid
is necrotic and infected, a CT scan should be performed and a needle passed into
the necrotic area under CT guidance, choosing a path that does not traverse
hollow viscera. If the aspirate is infected and the patient’s condition
deteriorating, then a laparotomy with débridement of the dead tissue around the
pancreas is appropriate .Because the process is progressive further necrotic
tissue may form, and the abscess cavity can either be drained and flushed
(Beget) (Fig. 55.29)
or repeated
laparotomies performed until there is a clean granulating cavity (Bradley).
Some of these patients are ill for long
periods of time. Nutritional support is essential. During the early phase of
disease parenteral nutrition is important and no advantage has yet been shown
for early enteral nutrition. However, once the phase of paralytic ileus has been
passed it is appropriate to commence nasojejunal feeding or feeding via a
jejunostomy placed in those who have undergone laparotomy. This has the effect
of reducing the risk of sepsis from parenteral feeding, and enteral feeding
restores the gut mucosal barrier preventing bacterial translocation through
the damaged mucosa.
Prognosis
of acute pancreatitis
For the patient with an acute mild episode the mortality should be less
than 1 per cent, while for the patient with a severe attack 20—25 per cent
mortality is anticipated. For those who have infected necrosis a mortality of up
to 50 per cent can be anticipated. There is a clear responsibility before the
patient is discharged to determine the aetiology of the attack of pancreatitis.
Gallstones must be treated, and the other causes, listed in Table 55.4,
must be excluded. The failure to remove a predisposing factor could lead
to a second attack of pancreatitis, which could be fatal.
Chronic pancreatitis is a chronic inflammatory
disease in which there is irreversible progressive destruction of pancreatic
tissue. Its clinical course is characterised by a dynamic progressive fibrosis
of the pancreas. In the early stages of its evolution it is frequently
complicated by attacks of acute pancreatitis that are responsible for recurrent
pain which may be the only clinical symptom. The incidence of chronic pancreatitis
in a prospective study in Copenhagen was 8.2 new cases per 100 000 population
per year, with a prevalence of 27.4 cases per 100 000. The incidence rates in
retrospective European, North American and Japanese studies range from two to
10 cases per 100 000 population per year. The disease occurs more frequently in
men (male to female ratio of 4:1) and the mean age of onset is about 40 years.
Pathology
and aetiology
At the onset of the disease when symptoms have
developed the pancreas may appear normal. Later the pancreas enlarges and
becomes hard as a result of fibrosis. The ducts become distorted and dilated
with areas both of stricture formation and of ectasia. Calcified stones weighing
from a few milligrams to 200 mg may form within the ducts. The ducts may
become occluded with a gelatinous proteinaceous fluid and debris-deformed cysts.
Histologically, the lesions affect the lobules producing ductular metaplasia and
atrophy of acini, hyperplasia of duct epithelium and interlobular fibrosis. The
most frequent cause of chronic pancreatitis is a high alcohol consumption. Other
causes are pancreatic duct obstruction resulting from stricture formation after
trauma, acute pancreatitis or even occlusion of the duct by pancreatic cancer.
Hereditary pancreatitis, infantile malnutrition and a large unexplained
idiopathic group make up the remainder. Amongst the idiopathic group there are
those who live in warm climates such as Kerala in southern India, and appear to
have a high incidence of pancreatitis. Here the pancreatitis begins at a young
age, is associated with a high incidence of diabetes mellitus and stone
formation is frequent. The importance of hereditary pancreatitis and
pancreatitis occurring at a young age is that there is an undoubtedly increased
risk of the development of pancreatic cancer, particularly if the patient smokes
tobacco heavily.
Clinical
features
Pain is the outstanding symptom in the majority
of patients. The site of pain depends to some extent on the main focus of the
disease. If the disease is mainly in the head of the pancreas then epigastric
and right subcostal pain is common, while if it
is limited to the
left side of the pancreas then left subcostal and back pain are the presenting
manifestations. In some patients the back pain predominates, while in others the
pain is more diffuse. Radiation to the shoulder, usually the left shoulder,
occurs. Nausea is common during attacks, and vomiting may occur. The pain is
dull and gnawing. The pain is both continuous and episodic, in that severe
bouts of pain may occur superimposed on background discomfort. All of the
complications of acute pancreatitis can occur with chronic pancreatitis.
Because of the pain weight loss is common, in that the patient does not feel
like eating. The pain prevents sleep and time off work is frequent. The number
of hospital admissions for acute exacerbations is a pointer towards the severity
of the disease. Analgesic use—abuse is frequent. This, too, gives an
indication
Investigation
Only in the early stages of the disease will
there be a rise in serum amylase. Pancreatic function tests merely confirm the
presence of pancreatic insufficiency or that more than 70 per cent of the gland
has been destroyed. Steatorrhoea affects more than 30 per cent of patients with
chronic pancreatitis.
The
prime investigation is either an MRI scan or a CT scan which will show the
outline of the gland, the main area of damage and the possibilities for surgical
correction. An MR cholangiogram will show the presence of biliary obstruction,
and an MR pancreatogram the state of the pancreatic duct. An ERCP or a
percutaneous pancreatogram (Fig. 55.30)
can elucidate the anatomy of the
duct and, in conjunction with the whole organ morphology, determine the type of
operation required, if operative intervention is indicated.
Treatment
A diet low in fat and with no alcohol is
advised. Pancreatic enzyme supplementation may reduce the frequency of painful
crises. Attention must he paid to nutrition to ensure that the patient gains
weight and takes an adequately varied and nutritionally appropriate diet. The
use of morphine
should be avoided and tobacco smoking
curtailed. There is no single therapeutic agent which has been shown to relieve
symptoms, although the use of antioxidants to mop up free oxygen radicals has
been tried.
The
role of surgery is in overcoming obstruction and removing mass lesions. Most
patients have a mass in the head of the pancreas, for which a resection of the
head of the pancreas either by a pancreatoduodenectomy or a Beget procedure
is appropriate. If the duct is markedly dilated, then a longitudinal
pancreatojejunostomy or Frey procedure can be of value (Fig.
55.31). The
rare patient with disease limited to the tail will be cured by a distal
pancreatectomy.
Prognosis
Correctly chosen surgery will relieve symptoms
in 75 per cent of patients provided that the aetiological factor is removed.
Development of pancreatic cancer is a risk in those who have had the disease
more than 20 years. New symptoms or a change in the pattern of symptoms should
be investigated and development of cancer excluded.