Diseases of the pancreas
The classification of pancreatitis has previously been made difficult owing to the description of various combinations of acute and chronic conditions with nomenclature that attempted to relate the classification to the aetiology. It is best to regard pancreatitis as either acute or chronic. Within these two broad divisions there are patients who may have recurrent episodes of acute pancreatitis and others who have chronic pancreatitis but who, in addition, experience attacks of acute pancreatitis (i.e. acute on chronic).
Acute pancreatitis is an acute inflammatory process of the pancreas, with varying involvement of other regional tissues or remote organ systems. This definition of acute pancreatitis was derived at a conference held in Atlanta in 1992 with the aim of providing a clinically based classification of acute pancreatitis and its complications. The Atlanta definition does not relate to either aetiology or pathological findings, as neither of these may be obvious to a clinician on first seeing a patient with the clinical features of acute pancreatitis.
The incidence of acute pancreatitis in the developed world has been demonstrating a progressive increase and it is estimated to be approximately 100 cases per 1 million people per year. However, this incidence will vary in different regions and is dependent on aetiological factors existing in a country. In countries with a relatively high consumption of alcohol, incidence of pancreatitis may be higher compared to countries with a low consumption of alcohol. Acute pancreatitis occurs most commonly in patients in the 30- to 60-year-old age group, with alcohol-related pancreatitis being more common in males and gallstone-related pancreatitis being more common in females.
Aetiology and pathogenesis
The causes of acute pancreatitis fall into three major categories: one third of cases are due to alcohol consumption; one third are secondary to gallstones; and one third are due to a variety of conditions that includes trauma, hyperlipidaemia, hypercalcaemia, miscellaneous drugs (e.g. thiazide diuretics), infections (e.g. mumps), tumours (e.g. ampullary tumours), sphincter of Oddi dysfunction, anatomical causes (e.g. pancreas divisum) or idiopathic (unknown) causes.
It is difficult to imagine that one single mechanism would explain the pathogenesis of acute pancreatitis given the diversity of the aetiological causes. However, all of these factors have one thing in common; that is, there is a triggering of activation of pancreatic trypsinogen to trypsin that then begins the process of autodigestion seen in all forms of acute pancreatitis.
The pancreas is the major organ in the abdomen producing digestive enzymes. These enzymes in their activated form break down the complex molecular structure of proteins, lipids and carbohydrates to yield simple amino acids, mono- and diglycerides plus glucose and fructose for subsequent absorption in the small intestine. This process takes place in the upper small intestine. The pancreatic enzymes are activated in the duodenum, where their action begins.
There are a number of protective mechanisms that prevent the pancreas from autodigestion by these powerful enzymes. Trypsinogen and the other proteolytic enzymes are secreted in their inactive form and do not become activated until they reach the duodenal lumen. The enzymes are formed in the acinar cells, and stored in zymogen granules within the cell. These membrane-lined granules protect the cell from any activated enzyme. Pancreatic acinar cells produce an antitrypsin molecule that further adds to the protection by an antagonist action on trypsin. Finally, the inactivated enzymes are secreted into the pancreatic ductules, are diluted by the richly alkaline fluid secreted by the ductular epithelium, and are rapidly propelled into the main pancreatic duct to be secreted into the duodenum, where they first come into contact with their specific activating factors (e.g. protein, carbohydrate, lipid).
Inappropriate activation of trypsinogen to trypsin within the pancreatic parenchyma will give rise to trypsin autodigestion of the pancreas and result in acute pancreatitis. It has been demonstrated that alcohol produces direct chemical damage to pancreatic acinar cells, particularly the membranes of the zymogen granules, thus allowing leakage of trypsinogen into the cell cytoplasm. Consequently, activation of the enzymes may occur, resulting in activation of an inflammatory cascade. Viral infections and drugs may have a similar mode of action. Gallstones cause pancreatitis when they pass from the gall bladder to the bile duct and then through the sphincter of Oddi into the duodenum (Endoscopic retrograde cholangiogram demonstrating the biliary system in a patient who presented with gallstone pancreatitis. The cholangiogram shows multiple small gallstones in the gall bladder and bile duct. Passage of one or more of the gallstones into the duodenum induced pancreatitis.). In some patients, there is a transient impaction of the stone at the sphincter. This may well result in abnormal motility of the sphincter, which raises the pressure within the pancreatic duct and retards flow. The elevated pancreatic duct pressure may cause some back pressure on the acinar cells, which in itself may cause their damage and re-activate trypsinogen. Another factor may be the back-flow of duodenal juice, which may be associated with sphincter dysmotility and further enhance trypsinogen activation within the pancreas.
Once trypsin has been activated, autodigestion of the pancreas begins. This injurious process sets up the normal inflammatory response, which is characterised by oedema, leucocytosis and increased vascularity. Furthermore, biologically active compounds of the cytokine system are activated and released into the circulation, resulting in effects on the heart, the surfactant of the lung and renal function.
The severity of an acute episode of pancreatitis is dependent on the severity of damage to the pancreas and the magnitude of the inflammatory response. Fluid may accumulate around the pancreas or extend beyond its immediate vicinity to involve the rest of the retroperitoneal space as well as small- and large-bowel mesentery. Fluid may also accumulate in the peritoneal cavity, initially in the lesser sac and posterior to the stomach, but, in more severe cases, ascites may develop. The degree of autodigestion may be of an extent that produces necrosis of a part or whole of the pancreas. The inflammatory process may affect adjacent organs, such as the colon, to reduce their mucosal barrier and allow migration (translocation) of bacteria to infect the necrotic tissue, thus forming an abscess. Oedema of the pancreas may also compress the bile duct and result in obstructive jaundice. Similarly, the oedema may obstruct the duodenum and result in an upper small-bowel obstruction, which will manifest as vomiting.
Necrosis of the pancreas and surrounding fatty tissue also results in deposition of calcium, which may result in a precipitous fall in serum calcium levels. In addition, with the massive shift of fluid that may occur with severe pancreatitis, there is a relative loss of fluid from the circulating volume, resulting in hypovolaemic shock.
Surgical pathology and complications
The pathological appearance of the pancreas in a patient with acute pancreatitis is that of an acute inflammatory condition characterised by oedema, increased vascularity and haemorrhage. In addition, and depending on the severity of an episode, an area of necrosis as well as scattered calcium deposits may be present. The pathological changes in acute pancreatitis represent a continuum, with interstitial oedema and minimal histological evidence of necrosis at the minor end of the scale, and confluent macroscopic necrosis at the other extreme. The complications of acute pancreatitis are subdivided into local and systemic (Complications of acute pancreatitis).
Acute pancreatitis is characterised by an acute episode of epigastric to central abdominal pain, usually of rapid onset. The pain often radiates into the middle of the back. In some instances the patient may complain of vomiting; however, this is not a constant feature. There may be a history of significant alcohol consumption (>40 g/day) or the presence of gallstones.
Examination reveals a person in distress from the pain and varying signs of shock, dependent on the severity of the attack.Vital signs may range from totally normal to severe hypotension, tachycardia and tachypnoea. Abdominal examination will reveal tenderness in the epigastrium, and, depending on severity, there may be signs of peritonism. A tender mass may be palpable and abdominal distension evident due to a developing ileus. In severe cases, flank ecchymosis (Grey-Turner sign) or periumbilical ecchymosis (Cullen's sign) may be seen.
The diagnosis of acute pancreatitis is made on the clinical features and demonstration of an abnormally elevated serum amylase. Amylase is one of the major enzymes of the pancreas. It is also present in salivary glands but has a different molecular size. Damage to the pancreas is associated with a release of amylase into the bloodstream, demonstrating a rapid rise in the serum level. The amylase is then rapidly cleared from the serum; therefore, the peak is only short-lived (i.e. 24 hours). For this reason, the rise in the amylase level does not correlate with the severity of pancreatitis because there is no way of predicting the timing of the sample to coincide with the peak amylase level.
Other enzymes have also been used for the diagnosis of pancreatitis, including serum lipase and serum trypsinogen levels. These investigations are more difficult to perform and, therefore, in most institutions, reliance is placed on serum amylase estimation. As all of these enzymes are cleared from the serum by the kidneys and excreted in urine, estimation of urinary enzyme levels (i.e. urinary amylase or lipase) can be used to assist in the diagnosis in patients where there may be some doubt. The peak rise for the urinary levels occurs 24–48 hours later than the serum peaks and hence allows for subsequent estimation.
The severity of pancreatitis is estimated by determining systemic criteria, which have been shown by carefully conducted studies to relate to outcome. The more of these positive systemic criteria, the greater is the severity of illness. These objective criteria are named after their originators and are known as Ranson or Imrie (Glasgow) scores. In addition, a more general score, which is also used for other severely debilitating conditions, is the APACHE II score, which may be used. If three or more of the Ranson/Imrie criteria or eight or more of the APACHE II criteria are abnormal, then pancreatitis is defined as severe. Criteria that are measured include systolic blood pressure, Pao2, creatinine, blood sugar level, urea, albumin, calcium, white cell count and level of liver transaminases. A positive score for each is registered when an abnormal value is detected within the initial 48 hours of the disease.
Structural changes of the pancreas may be demonstrated using computed tomography (CT), and when this is combined with contrast to perform a contrastenhanced CT scan, areas of necrosis can be visualised, thus determining the degree of local complications.The optimal time for the CT is approximately 5 days after the onset of the disease (A contrast-enhanced CT scan in a patient with severe acute pancreatitis. It demonstrates an area of hypoperfusion that reflects necrosis of the pancreas.). CT scan is also used to determine the presence or absence of fluid collections and pseudocysts. Ultrasound is used to determine any evidence of gallstones in the gall bladder.
The treatment of a patient with acute pancreatitis is directed four ways: general, local, complications and cause.
Depending on the severity of the fluid loss, patients with acute pancreatitis are treated for their fluid loss and given appropriate cardiovascular support. In the most common situation of mild pancreatitis, this consists of intravenous fluid replacement via a peripheral intravenous line. However, in severe pancreatitis, careful fluid replacement with central venous pressure measurements may be necessary. Oxygen is given via nasal mask or speculum as hypoxia is a common association of acute pancreatitis. In addition effective pain control needs to be ensured, and usually this means administration of parenteral opiate analgesics such as morphine.
There is no specific treatment for the pancreatic inflammation. Therefore, treatment is directed at minimising the progression of the disease and preventing complications. Initially, the patient is fasted; however, enteral feeding has been shown to minimise the fastingassociated breakdown of the gut mucosal barrier and hence prevent bacterial translocation. Furthermore, enteral nutrients have been shown to decrease the incidence of pancreatic abscess formation in patients with severe pancreatitis. Consequently once it has been determined that the pancreatitis is severe nasoenteric feeding is commenced. In some instances it may not be possible to deliver the total nutritional needs of the patient via the enteral route, because the ileus, which accompanies the inflation, limits the volume of the feed. In such circumstances parenteral nutrition is added to supplement the patient's needs.
Early studies in the management of acute pancreatitis have not shown a role for antibiotics. However, recent studies that have used antibiotics whose effects are concentrated in the pancreatic parenchyma (imipenen) have shown a decrease in complications. Consequently, prophylactic antibiotics that are taken up by the pancreatic parenchyma are used in patients demonstrating evidence of pancreatic necrosis on CT scan. Antibiotics are also used if there is clear evidence of infection.
Complications are treated as they arise and often require surgery via an endoscopic, percutaneous or open approach. Surgical intervention in pancreatitis is reserved for the treatment of complications and in gallstone pancreatitis for the treatment of the cause.
In severe pancreatitis with infected necrosis, there is a need for operation to debride the pancreas of infected necrosed tissue. Infection may be diagnosed from either the presence of gas in the necrosed tissue as demonstrated by CT or the presence of organisms in tissue that has been aspirated from the pancreas following a percutaneous radiologically guided needle approach. Pancreatic abscesses may be drained via percutaneous techniques but usually require open surgical drainage. Pseudocysts are treated either by a combination of percutaneous and endoscopic techniques, or by open surgery.
In severe acute pancreatitis of a biliary cause (i.e. gallstones), acute intervention by endoscopic retrograde cholangiopancreatography (ERCP) often demonstrates the cause (i.e. a stone), and treatment by endoscopic sphincterotomy results in a greatly improved outcome for these patients when compared to either a more conservative approach or intervention by open surgery.
In one third of patients with acute pancreatitis, the cause is gallstones that pass from the gall bladder into the duodenum. Following recovery from an acute attack of pancreatitis, the patients are treated by cholecystectomy, which in the majority is done via a laparoscopic approach. No further episodes of pancreatitis occur after cholecystectomy.
In patients with the rare cause of sphincter of Oddi dysfunction, division of the sphincter of Oddi is also associated with cure. In patients where the cause is alcohol consumption, abstinence is accompanied with a decreased frequency and ultimately cure of pancreatitis. However, in many instances alcohol addiction is a major problem and patients require much community and social support before abstention is achieved.
Thus acute pancreatitis is a debilitating acute abdominal disorder that, in the majority of patients, has a benign outcome when appropriately diagnosed and treated. In a small number of patients the disease may be severe and may be associated with complications that ultimately may lead to the patient's death. The progression of the disease is unpredictable, hence all patients given the diagnosis of acute pancreatitis should be observed carefully in the initial period and a severity score determined. Once the severity of the disease is defined, appropriate treatment can be given.
Chronic pancreatitis is a fibrotic disease of the pancreas that is characterised by recurrent episodes of abdominal pain, and gastrointestinal symptoms and signs of malabsorption. In some patients, involvement of the islet cells also results in diabetes.
Aetiology and pathogenesis
The most common cause of chronic pancreatitis in Australia and other developed countries is chronic alcohol abuse. Less commonly, three other forms of chronic pancreatitis may be seen: hereditary, nutritional and distal pancreatitis.
Hereditary pancreatitis is a disease of recurrent inflammation of the pancreas that leads to chronic pancreatitis. The disease occurs in blood relatives across at least two generations. It is an autosomal dominant condition with variable expression and the first attack of pancreatitis usually occurs in childhood. Nutritional pancreatitis is also known as tropical pancreatitis and fibrocalcific pancreatic diabetes. It is a non-alcoholic form of calcific pancreatitis and occurs in young adults in low-income populations of developing nations. Recurrent attacks begin in early childhood. Distal pancreatitis occurs following trauma to the pancreas (e.g. after a motor vehicle accident).
The pathogenesis of chronic pancreatitis is probably different for each form of the disease, and an underlying theory does not exist. A number of mechanisms have been proposed in the pathogenesis. Hypersecretion of pancreatic enzymes is thought to be one cause. These enzymes precipitate in the ducts, forming plugs that may calcify and cause obstruction. An alternative suggestion is that the plugs form as a result of high concentrations of intraductal mucoproteins, or clusters of desquamated epithelial cells associated with a high viscosity of pancreatic juice. A direct toxic effect of alcohol on pancreatic lipids has also been proposed as a pathogenic mechanism. Following destruction of lipidcontaining membranes of the cells there is cell necrosis, which over the years leads to chronic pancreatitis.
Surgical pathology and complications
The pancreas of a patient with chronic pancreatitis is typically fibrosed and reduced in size (atrophied). There is extensive calcification throughout the parenchyma. Initially, the pancreatic islet cells are preserved; however, with progressive atrophy, these may also become involved in the process and atrophy. The pancreatic ducts develop multiple strictures and demonstrate post-stenotic dilatation. Calcified calculi may be found within the ducts.
Complications of chronic pancreatitis include the formation of a pseudocyst when an acute episode is superimposed on the chronic disease. In view of the atrophy, malabsorption and diabetes may result.
Patients with chronic pancreatitis present with recurrent episodes of epigastric abdominal pain that radiates into the back. These episodes of pain occur over a prolonged period and, in alcohol-related pancreatitis, initially occur after bouts of heavy drinking. However, as the disease progresses, episodes of pain also occur independently of alcohol consumption. In due course, the pain may be constant, with more severe attacks occurring intermittently. The pain at its worst is very debilitating because the patient often cannot find a position of comfort and needs high doses of parenteral analgesia for relief. The disease may be associated with varying degrees of malabsorption characterised by steatorrhoea and weight loss. In addition, symptoms and signs of diabetes may develop.
The diagnosis is made on the characteristic presentation plus confirmatory radiological investigations. Serological tests, in particular serum amylase, may be entirely normal in chronic pancreatitis. A plain abdominal X-ray may reveal calcification in the region of the pancreas. This may be confirmed by CT scanning, which may also show direct dilatation and atrophy of the pancreas. The most specific investigation is an ERCP. In patients with moderate to severe pancreatitis, changes will be demonstrated in the pancreatic duct. These changes include stricture formation and duct dilatation. Pancreatic calculi may also be demonstrated.
The only useful test of pancreatic function is the measurement of faecal fat content to determine whether the patient has significant steatorrhoea. This is usually done by collecting faeces for 3 days and measuring the fat content of the faeces in the laboratory. An abnormal amount of faecal fat supports the diagnosis of malabsorption. A number of other tests of pancreatic enzyme function have been developed, but all are invasive and require prolonged study, thus making their indication of low value.
Chronic pancreatitis is one of the most difficult abdominal conditions to treat as there is no specific treatment for the ongoing chronic inflammatory disease and treatment is largely aimed at the symptoms and complications.
For alcoholic patients, it is crucial that they abstain from alcohol consumption; otherwise no other form of treatment will be effective. It is important to realise that in alcoholic patients, the epigastric pain experienced after heavy drinking may not be solely due to pancreatitis and may be caused by alcoholic gastritis. Therefore, antacid therapy and treatment with gastric acid suppressing medication is important.
The role of surgery in the treatment of chronic pancreatitis is limited and confined to those patients in whom it can be demonstrated that the cause is nonalcoholic or who have abstained from alcohol.
Because pain is the major symptom of chronic pancreatitis, measures that aim to alleviate this are usually taken. Administration of oral pancreatic enzyme replacement medication reduces the hormone drive on the pancreas and may assist in the control of pain, in addition to appropriate oral analgesics. The pancreatic enzyme replacement therapy will also treat the steatorrhoea and assist with the treatment of malabsorption.
Surgery in chronic pancreatitis is usually aimed at relieving an obstruction to pancreatic secretion, by either removing stones and debris from the duct or bypassing a stricture. In patients with a dominant pancreatic duct stricture and a dilated duct, a bypass operation between the duct and small bowel (Puestow procedure) is often effective in relieving symptoms and improving malabsorption. Unfortunately, in many patients single strictures are uncommon and what is more likely are multiple strictures throughout the gland, making bypass surgery inappropriate.
Placement of a plastic stent in a pancreatic duct with multiple strictures has been associated with relief in some patients and this technique may be appropriate for a group of patients with chronic pancreatitis.
For some patients the extent of the disease is such that only removal of a large part of the pancreas can alleviate the symptoms. This may require either a Whipple, pancreatoduodenectomy resection or a newer operation that removes the head of the pancreas whilst preserving the duodenum (Beger operation).
Chronic pancreatitis in Western countries is mainly a self-inflicted disease with disastrous results for the patient because it is difficult to treat specifically. In patients who abstain from alcohol the symptoms of pain may be relieved by surgical bypass or stenting of the duct or by resection of the part of the pancreas in which the disease predominates.
Among all of the cancers, pancreatic cancer has one of the worst reputations and, despite improvements in both diagnostic and surgical techniques, survival has not significantly improved during the past 50 years. Furthermore, unlike most other cancers, its incidence appears to be increasing and, in certain parts of the world, including Australia, it has an incidence approaching 100 per million of population per year.
The incidence of pancreatic cancer is greater in males compared with that in females, and in general is a disease of people in their seventh decade and older. The poor outcomes may relate to the fact that it often presents late and after there has been spread of the disease beyond the pancreas.
Aetiology and pathogenesis
The cause of cancer of the pancreas is unknown. The only environmental factor associated with cancer of the pancreas has been cigarette smoking. There have not been any dietary factors conclusively associated with the development of pancreatic malignancy. A recent multicentre study has demonstrated that patients with chronic pancreatitis, which primarily has an alcohol aetiology, have an increased risk of developing cancer (the rate being 4%).
As in many other malignancies, alterations in cell genes are thought to be the basis of cancer development in the pancreas. Alterations have been demonstrated in the ras oncogene family and the p53 tumour suppressor gene. However, their significance in either the aetiology or development of pancreatic cancer is not known.
Growth factors and their receptors have been demonstrated to be important in the biological behaviour of pancreatic cancer. A number of tissue growth factors have been associated with the growth of the cancers, including epidermal growth factor (EGF) and tumour growth factor-alpha (TGF-α). In addition, a number of gastrointestinal and other hormones have been associated with tumour growth. These include cholecystokinin, secretin, oestradiol, progesterone and testosterone. The significance of these growth factors and hormones in the development of pancreatic cancer is also not known. However, an understanding of the molecular basis of these tumours may provide new markers for diagnosis, for prognosis and ultimately for therapy.
Surgical pathology and complications
Cancers of the pancreas are subdivided into different types, depending on their site and histological type. While the majority of pancreatic cancers are adenocarcinomas of the main pancreatic gland, it is important to identify the rarer cancers because these have a much better prognosis after successful excision.
Adenocarcinoma cancers originate from the ductular lining and usually occur in the head of the pancreas. Less commonly they may arise in the body or tail of the gland. Owing to the extensive vascularity of the pancreas, metastatic spread occurs early in the evolution of the disease. Metastases initially spread to the draining lymph nodes in the region of the coeliac axis and may involve the sensory nerves in this area. Cancer metastases also preferentially involve the liver and, in more advanced cases, there may be spread throughout the peritoneal cavity.
Ampullary cancers are adenocarcinomas that originate in the region of the ampulla of Vater, which is made up of the intraduodenal components of the bile duct and pancreatic duct as well as their common channel. These tumours have a lower malignant propensity when compared to cancers of the head and body of the pancreas and thus have a much better prognosis following surgical excision. However, this may reflect the fact that due to their position diagnosis is made early in the evolution of the disease. Ampullary cancers are not a common malignancy; however, when they do occur it is important that diagnosis be made early because surgical resection can be curative.
Cystic tumours are quite rare lesions of the pancreas, representing 1% of malignant neoplasms of the pancreas. Histologically, they range from benign tumours of adenomatous appearance to cystadenocarcinomas. The tumours may have either mucous or serous fluidcontaining cysts; the former having a greater malignant propensity. Recognition and differentiation from benign cysts is important because surgical excision is associated with cure.
The typical presentation of a patient with adenocarcinoma of either the ampulla or the pancreas is a person with ‘painless jaundice’. There may also have been a period of anorexia with associated weight loss. The patient may report pale-coloured stools, occasionally said to have silver streaks on their surface. In addition, the urine is dark and the skin yellow. On examination, an abdominal mass may be detected; however, more commonly the tumour will not be palpable. A distended gall bladder may be palpated under the right costal margin and this sign in a patient with painless obstructive jaundice is strongly suggestive of a malignant pancreatic cause (Courvoisier's Law).
In patients in whom the bile duct is not involved early in the disease, presentation may be due to early spread of the tumour and resulting pain in the epigastrium or mid-back. Pain is a poor prognostic factor in a patient with pancreatic cancer because it invariably signals spread of the disease.
Patients with pancreatic malignancy usually present with symptoms and signs of obstructive jaundice. Therefore, investigations are directed at the differential diagnosis of this condition. Ultrasound examination will demonstrate a dilated extrahepatic biliary system, often with dilated intrahepatic ducts and a distended gall bladder. Depending on its size, a mass may be seen in the head of the pancreas.With ampullary tumours a mass will not be detected but the pancreatic duct may be seen to be dilated.
The most precise investigation, providing the most information, is endoscopic retrograde cholangiopancreatography (ERCP). This endoscopic procedure allows for direct visualisation of the ampulla, and after cannulation of the bile and pancreatic ducts, contrast may be injected into the ducts and X-rays taken to visualise any signs of obstruction. Cancer of the head of the pancreas shows a characteristic narrowing of both ducts on ERCP (the double duct sign).
Biopsy of any visualised abnormality, or cytology from the strictured areas, can provide histological confirmation of the diagnosis. Computed tomography (CT) scanning may demonstrate a mass in the pancreas, but often small masses may not readily be seen. For larger masses and when histological confirmation is needed prior to treatment, a percutaneous biopsy may be done under either CT scan or ultrasound guidance.
Serum tumour markers have been used for the diagnosis of various abdominal neoplasms. The tumourassociated antigen CA19-9 has been extensively investigated to assess its role in the diagnosis of pancreatic cancer. This antigen is certainly detected in the serum of patients with pancreatic cancer, and there appears to be a direct correlation between tumour size and level of CA19-9. However, its specificity is low as is its sensitivity for small tumours. Its main value currently is in the follow-up of patients with high values to assess response to treatment.
The only form of therapy that potentially may cure patients with cancer of the pancreas is surgical resection. For surgery to be effective early diagnosis is essential in order to detect lesions of relatively small size. Put another way, the best surgical results are achieved in patients with small tumours. In general, a diameter of 3 cm or less will be resectable and potentially give the best outcome. Due to their position, ampullary cancers tend to present earlier than cancers of the rest of the pancreas and, consequently, have the best outcome following surgery. In addition, surgical removal of cystic tumours is associated with an excellent outcome. Cancers of the body of the pancreas tend to present late and, in general, are not resectable. Similarly, most cancers of the head of the pancreas are not resectable for cure. Occasionally, however, they may become symptomatic early and can be resected with good results.
Thus, despite the generally gloomy picture regarding the curative treatment of these cancers, it should be remembered that for certain tumours curative resection is possible and all attempts should be made to identify these patients and not place all patients in the incurable category.
For the majority of patients with cancer of the pancreas, treatment is directed at palliation. The most common presentation is that of obstructive jaundice, which is associated with anorexia and pruritus. Treatment that aims to relieve the obstruction relieves the pruritus and also improves the patient's well-being. The life expectancy of a patient with an inoperable cancer of the pancreas is approximately 10 months. Therefore, the aim of palliation is to do the least invasive procedure that will achieve drainage of the bile duct and relieve the obstructive jaundice.
In the majority of patients excellent palliation is achieved by inserting an endoprosthesis (stent) through the obstruction using an endoscopic approach. The stent drains bile from the proximal bile duct into the duodenum and the jaundice is relieved. If the endoscopic approach is not successful a percutaneous route through the liver may be used to place the stent. However, in general, the morbidity and results of this approach are not as good as the endoscopic route. The advantage of the endoscopic and percutaneous treatment is the fact that it avoids the need for laparotomy, and the patient's recovery is therefore rapid. It should be emphasised that this procedure should only be used in patients in whom pre-operative investigations have determined that the tumour is inoperable.
Surgical bypass of the tumour to drain the biliary tract and relieve the jaundice is done in patients who have undergone laparotomy to assess resectability but in whom curative resection was not possible. Patients with inoperable cancers often inquire about the use of chemotherapy and radiotherapy, but these treatments have not been shown to be effective in the treatment of pancreatic cancer. It should be remembered that unless it can be shown that these forms of treatment can prolong survival they should not be used because there are significant side effects.
Most patients with pancreatic cancer will develop pain, especially in the terminal stages of the disease. Modern analgesics and techniques that aim to inhibit sensory transmission are effective in controlling this debilitating symptom, and patients should be informed of their availability in order to avoid unnecessary suffering.
The operation done for cure of ampullary or head of pancreas cancers is a pancreaticoduodenectomy (Whipple procedure; Pancreaticoduodenectomy, which consists of partial gastrectomy, partial pancreatectomy, and excision of the distal bile duct and all of the duodenum.). In this operation the head of the pancreas and adjacent duodenum plus lower bile duct and half the stomach are removed. This extensive surgical resection ensures that not only is the tumour removed but also the adjacent lymph nodes. The pancreas, bile duct and stomach are reanastomosed and thus continuity is re-established. This operation had a bad reputation in the past; however, with modern surgical techniques the operative mortality and morbidity is low and is now advised for patients with operable tumours.
Palliative bypass operation (Palliative bypass of the bile duct and stomach in a patient with a non-resectable pancreatic cancer. (A) Choledochojejunostomy, (B) gastroenterostomy, (C) entero-enterosotomy.) consists of an anastomosis between the dilated bile duct and a segment of the small intestine. Occasionally, the gallbladder may be used for the bypass instead of the bile duct. In addition, a prophylactic bypass of the duodenum may be done via a gastroenterostomy in order to prevent the vomiting that may occur in approximately 30% of patients due to duodenal obstruction in the terminal stage of the disease.
The overall survival of patients with pancreatic cancer is poor, with less than 5% survival at 5 years from diagnosis. However, in patients having successful curative resection, survival is greater than 30% at 5 years, and for patients with ampullary tumours it is greater than 50%. Patients with cystadenomas have the best results, with cure reported in the majority of patients.Pancreatic cancer is one of the worst malignancies in terms of outcome following diagnosis and treatment. Undoubtedly, early diagnosis when the tumour is differentiated and of a smaller size is associated with a better outcome. Surgical excision remains the best available therapy and only chance for cure.