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 frequently severe or even agonising, it is refractory to the usual doses of analgesics, and constant in nature and intensity. Pain is usually experienced first in the epigastrium but may be localised to either upper quadrant or felt diffusely throughout the abdomen. There is radiation to the back in about 50 per cent of patients and some patients may gain relief by sitting or leaning forwards. The suddenness of onset may simulate a perforated peptic ulcer, while biliary colic or acute cholecystitis can be mimicked if the pain is maximal in the right upper quadrant. Radiation to the chest can simulate myocardial infarction, pneumonia or pleuritic pain. In fact, acute pancreatitis can mimic most causes of the acute abdomen and should seldom be discounted in differential diagnosis. The diagnosis must always be considered in a patient who suddenly develops shock or anuria regardless of whether they have abdominal pain.

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 10—20        per cent of patients. Pulmonary oedema and pneu­monitis are also described and may give rise to the differen­tial diagnosis of pneumonia or myocardial infarction. The patient may be confused and exhibit the signs of metabolic derangement together with hypoxaemia.

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 the severe attack involves full resuscitation, and strict asepsis should be observed in the placement of all monitoring lines. If there is evidence of cardiocirculatory compromise then a Swan—Ganz catheter should be inserted in order to measure pulmonary artery wedge pressure, cardiac output and sys­temic resistance (see Chapter 4). Regular arterial blood gas analysis is essential as the onset of hypoxia and acidosis may be detected late by clinical means alone. The techniques evolved in the critical care environment should be applied to the patient with pancreatitis. The patient should be made comfortable, appropriately sedated and adequate analgesics given. Specific therapy such as the administration of aprotinin, somatostatin and platelet-activating factor inhibitors has failed to improve prognosis in numerous clinical trials and should not be given. There is some evidence to support the use of prophylactic antibiotics in the prevention of local and other septic complications. Intravenous cefuroxime or imipenem is advised. If gallstones are the aetiology of severe pancreatitis, an urgent ERCP is indicated to exclude the presence of a stone stuck in the ampulla of Vater if there is no improvement in the general condition of the patient within 48 hours. The presence of cholangitis with abnormal liver function tests is an indication for urgent endoscopic intervention. Complications

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

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 of the severity of the disability. The patient’s lifestyle will gradually be destroyed by pain, analgesic dependence, weight loss and inability to work. Complications frequently bring the patient to the attention of the surgeon. Infection is not infrequent, possibly related to the increasing incidence of diabetes mellitus with time. Loss of exocrine function will occur leading to steatorrhoea which can be debilitating without supplementation, whilst loss of endocrine function and the development of diabetes are not uncommon, and the incidence increases as the disease progresses.

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.