Carcinoma of the pancreas

Pancreatic cancer is the eighth most common cancer causing death in the UK. The incidence is 10 cases per 100 000 population per year. The incidence has risen steadily over the last 25 years, until 5 years ago when it levelled off. The disease is a disease of ageing, with the average age of death in men being 74 years and that in women 79 years. It affects men and women to the same degree. Predisposing factors are tobacco smoking and chronic pancreatitis. No other relationships have been elucidated.

Pathology

More than 85 per cent of cases are duct cell adenocarcinornas. The remaining tumours are a fascinating variety of pathologies, each with their own characteristics. The more common tumours are listed in Table 55.8. The importance of the pathology is that some tumours have a prolonged natural history, for instance, the cystadenocarcinomas, while those with an ampullary tumour (Fig. 55.32) or a neuroendocrine have an increased survival after resection.  

Clinical features

The most frequent symptoms are nonspecific, namely epigastric discomfort, anorexia and weight loss. Often the patient is aware of their digestion for the first time in their life, and such is the mildness of the initial symptoms that they are frequently dismissed both by patient and by doctor. Jaundice is the commonest sign and symptom which brings the patient to the attention of his or her physician. Some 85 per cent of patients present with this symptom. It is characteristically painless jaundice but may be associated with nausea and epigastric discomfort. Change of bowel habit is rare.

On examination there is frequently evidence of weight loss, a palpable liver, a palpable gall bladder and even metastatic lymph nodes in the neck. Courvoisier first drew attention to the association of an enlarged gall bladder and a pancreatic tumour in 1890, when he stated that when the common duct is obstructed by a stone dilatation is rare; when the duct is obstructed in some other way, dilatation is common. In those days dilatation of the duct could not be determined and the dilatation, thus, refers to the gall bladder. Other signs of intra abdominal malignancy should be looked for with care, such as a mass, ascites and tumour deposits in the pelvis.

Investigation

If the patient is jaundiced, the usual blood tests and ultrasound scan should be performed. This will determine whether or not the bile duct is dilated. If it is and there is a genuine suspicion of a tumour in the head of the pancreas, the preferred test is now a contrast enhanced spiral CT scan specific for the pancreas. The next investigation is that of an endoscopic examination to determine whether the jaundice can be relieved endoscopically. If it can, a stent should be inserted through the stricture to relieve the jaundice. Attention should be paid to the coagulation to ensure that no bleeding occurs during this process. If the ERCP shows the

characteristic features of a tumour and the CT scan shows that the tumour is small (less than 4 cm), and confined to the head of the pancreas without evidence of distant spread or vascular invasion, then the patient should be considered for operative intervention and their state of general fitness assessed. More accurate information can be obtained by endoscopic ultrasound in which the ultrasound probe on the end of an endoscope is used to obtain images of the tumour via the duodenum, giving good definition of the tumour and its extent. Unfortunately, lymphadenopathy is not well shown by this technique, but it is possible to determine with accuracy whether or not the portal vein is involved.

Management

At the time of presentation, 90—95 per cent of patients are unsuitable for resection because of either local spread into the superior mesenteric vein, para aortic or mesenteric lymphadenopathy, or hepatic metastases. In some patients age precludes major operative intervention. For those patients who are inoperable palliative treatment should be offered. Jaundice is relieved by stenting. Obstruction of the duode­num occurs in approximately 15 per cent; if this occurs early in the course of the disease surgical bypass by gastrojejuno­stomy is appropriate, but if it is late in the course of the disease then the use of expanding metal stents inserted endoscopically is preferred as many of these patients have prolonged delayed gastric emptying following surgery. If the patient is not a suitable candidate for endoscopic biliary stenting a percutaneous transhepatic stent can be placed. In younger patients who may have a better prognosis a laparotomy to assess the tumour can be appropriate; if the tumour is proved inoperable a choledochoduodenostomy and gastro­jejunostomy is the preferred approach, but the simpler chole-cystjejunostomy (Fig. 55.33) is more frequently performed. The disadvantage of the latter technique is that bile must drain through the cystic duct which is narrow, and if the cystic duct is inserted low into the bile duct it is vulnerable to occlusion by tumour growth. Any patient who has palliative treatment should have a biopsy performed to obtain histological verification. If operation is undertaken this can be done at the time of the operation, but if no operative procedure is undertaken a percutaneous trucut biopsy of the tumour should be performed.

The role of chemotherapy in the management of pancreatic cancer remains ill defined. If the tumour is a lymphoma then benefit is without doubt. Lymphomas of the pancreas are rare, however, comprising less than 3 per cent of the total number of pancreatic cancers. For the duct cell adenocarcinoma, 5-fluorouracil (5FU) or gemcitabine will produce a remission in 15—25 per cent of patients, whilst the remainder will have no benefit from the therapy. In those that have a remission prognosis is extended by approximately 6 months. No long-term cures have been described with oncological agents.

Surgical resection

If a cystic tumour is encountered, no matter how large, most of these can be removed surgically with a reasonable chance of cure and with low operative mortality. Tumours of the ampulla have a good prognosis and should, if at all possible, be resected. Some of the rare tumours and the neuroendocrine lesions should also be resected if at all possible. Patients with duct cell cancers which are less than 4 cm in diameter, not involving the superior mesenteric or portal veins and with no evidence of multiple enlarged nodes or distant spread, should be considered for a resection. The appropriate resection is that of a pylorus-preserving pancreatoduodenectomy with a local lymphadenectomy. Extended resections have not been shown to be beneficial in improving survival and are associated with an increased morbidity.

The operation can now be performed safely with a mortality of 3—5 per cent. The morbidity remains high with some 40 per cent of patients developing a complication in the postoperative period. These complications are usually infec­tive, but a leak from the pancreatic duct is known to occur in at least 10 per cent of patients and this may give rise to major complications. The role of adjuvant radiotherapy and chemotherapy with resection has not been elucidated.

Pancreatoduodenectomy preoperative management. A full assessment of the patient’s general condition should be carried out and a decision made whether or not to relieve the jaundice preoperatively. Occasionally, if the period of jaundice is short (2 weeks), it is safe to proceed to operation, but if the period of jaundice is prolonged and a more detailed preoperative assessment of operability is required then a stent allows more time and relieves the symptoms associated with jaundice. The clotting should be carefully checked pre­operatively and adequate hydration ensured. A full explanation is made to ensure that the patient is aware of the diagnosis, the gravity of the operation and the risks involved, and consent taken.

Under general anaesthesia with adequate monitoring, the abdomen is explored and operability assessed. If the tumour is localised and without distant spread then resection is appropriate. A cholecystectomy is performed. The bile duct is dissected together with the structures in the porta hepatis, removing the lymphatic tissue in this area. This will expose the hepatic artery and enable division of the gastroduodenal artery which will expose the portal vein. The duodenum and right colon are mobilised from the retroperitoneal tissues and the fourth part of the duodenum is dissected and freed from the ligament of Treitz so that the upper jejunum can be brought into the supracolic compartment. The jejunum is divided and the mesentery of the proximal jejunum detached. The proximal duodenum is divided. The neck of the pancreas is divided and then the uncinate process separated from the superior mesenteric artery and vein working up towards the upper bile duct which is divided releasing the specimen (Fig. 55.34). Retroperitoneal lymph nodes are completely removed with the specimen as are those attached to the superior mesenteric vessels. Reconstruction is carried out as in Fig. 55.35. The operation should take between 3 and 6 hours. Blood loss should be low and transfusion unnecessary. Neither duct is stented and a single drain to the subhepatic space should be kept in situ for 4 days.

  Prognosis

The overall median survival for patients with pancreatic cancer is 20 weeks. Less than 3 per cent of patients will survive for 5 years. Patients with a carcinoma of the ampulla of Vater who have had a resection will have a 5-year survival rate of 40 per cent, while those with a duct cell carcinoma will have a 5-year survival rate of 20 per cent. More ‘benign’ tumours will, of course, have a better prognosis. Following surgery all patients who have had palliative treatment require regular follow-up in order to care for steatorrhoea with enzyme supplementation, diabetes mellitus, if it develops, with oral hypoglycaemics or insulin as appropriate, and pain with either analgesics or an appropriate nerve block. The procedure of transthoracic splanchnicectomy is now the preferred procedure for relieving the pain and should be considered in preference to a coeliac plexus block.