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Periampullary Cancer
PANCREAS
What’s new
Periampullary Cancer
• Endoscopic ultrasonography is useful for detecting small pancreatic lesions when resection equates with cure • Portal vein resection is safe, but its long-term benefit remains unclear • Recent studies suggest that extended lymphadenectomy is of little value
Rob Hutchins R C N Williamson
Epidemiology and aetiology
useful in borderline cases (Figure 1). The latest multi-slice scanners may further improve assessment. • ‘Single-stop’ MRI and magnetic resonance cholangiopancreatography have not been shown unequivocally to be superior to CT. • Most surgeons would not advise percutaneous tissue biopsy diagnosis preoperatively, because of the risk of tumour seeding and the high detection rate of cancers in the presence of pancreatic and biliary strictures. The role of linear probe endoscopic ultrasound-guided biopsy has not been defined. • Staging laparoscopy with or without laparoscopic ultrasonography may reduce unnecessary laparotomies. However, it is probably of cost and patient benefit only in selected cases (pancreatic head and body cancers, not ampullary lesions).
The periampullary cancers comprise duodenal, ampullary and distal bile duct cancers; the most common is ductal carcinoma of the pancreas, which has a prevalence of 10/100,000 population. The incidence of distal bile duct cancers is increasing. Smoking, diabetes mellitus, chronic pancreatitis, male gender, greater age, hereditary pancreatitis and familial cancer syndromes predispose to pancreatic cancer. Duodenal cancer may arise from the polyps found in familial adenomatous polyposis. Ampullary cancers generally arise from pre-existing adenomas, and bile duct cancers are associated with primary sclerosing cholangitis, ulcerative colitis, papillomatosis, choledochal cysts, and anomalous junction of the pancreatic and biliary ductal systems.
Clinical features Management
Obstructive jaundice is the most common presentation of periampullary cancer. There may be associated weight loss, anorexia, pain or cholangitis. Duodenal and ampullary cancers may present with anaemia secondary to gastrointestinal bleeding. Pancreatic cancers may also present with paraneoplastic syndromes.
Preoperative biliary stenting is commonly practised in the UK. It is performed because of delays in referral, limited time for investigation and theatre restrictions. There is little evidence that routine preoperative stenting is beneficial, but any suspicion of cholangitis demands urgent decompression of the bile duct (Sohn et al.). Stenting is usually undertaken by the endoscopic route or, if this fails, percutaneously by the transhepatic route. Surgical resection is the only potential cure. Almost all patients undergo pylorus-preserving proximal pancreaticoduodenectomy (PPPP, Figure 2). This operation is as adequate as a conventional Whipple’s resection (which includes distal gastrectomy), but some units continue to perform the older procedure routinely and others offer it selectively on the basis of tumour spread. There are now few indications for total pan-
Investigations • Ultrasonography identifies biliary obstruction and, more importantly, the level of obstruction. It can miss a pancreatic head mass, but shows advanced disease with liver metastases. • Endoscopic retrograde cholangiopancreatography demonstrates both pancreatic and biliary strictures, and enables diagnostic brush biliary cytology (only 50% sensitivity) and therapeutic plastic stenting to relieve jaundice. Investigation centres on local and regional staging. • Spiral CT using a pancreatic protocol shows relative tumour hypoperfusion, disease dissemination and vascular invasion. • Bone scintigraphy is unhelpful unless specific new bony pain is evident. • CT of the chest is not cost-effective compared with simple plain radiography. • Endoscopic ultrasonography may show venous involvement better than CT, but is less useful for arterial encasement. • As CT has improved, many centres have abandoned arteriography for the assessment of vascular invasion, but it remains
Rob Hutchins is Consultant General and Hepatopancreatobiliary Surgeon at the Royal London Hospital, London, UK.
1 CT scan showing a large pancreatic head mass encasing the superior mesenteric vein (contrast-enhanced vessel in the middle of the mass). The distended gallbladder and adjacent duodenal loop are clearly visible.
R C N Williamson is Consultant Surgeon at Hammersmith Hospital, London, UK, Professor of Surgery at Imperial College, London, and Dean of the Royal Society of Medicine.
MEDICINE
126
© 2003 The Medicine Publishing Company Ltd
PANCREAS
a
b
2a The line of division of the neck of the pancreas is seen between the silk (black) sutures from the superior mesenteric vein (below) to the portal vein (above). The common bile duct ready for division is slung with an orange tape and the transfixed gastroduodenal artery is held between forceps. b The resected specimen. (By courtesy of Dr R Hart, Toronto, Canada.)
createctomy. Portal vein/superior mesenteric vein involvement is generally regarded as unresectable. Portal venous resection and reconstruction can be achieved with a low mortality, but this procedure is not often performed; its value is undetermined because of scarce information on tumour size, histological venous invasion and long-term outcome. Extended lymphadenectomy, including coeliac, superior mesenteric and para-aortic nodes, can be performed by an expert with little additional morbidity, but evidence of long-term survival benefit is awaited. Palliation usually comprises biliary decompression and analgesia. Biliary stenting may have a lower peri-procedure mortality than surgical bypass, but further hospital admissions may be required for stent blockage. In specialized centres, surgical bypass can be achieved with little or no mortality (Isla et al.). Survival is similar with the two methods. Mesh metal stents may have a higher patency rate, which becomes more important as new chemotherapeutic agents are developed and survival is prolonged. Surgical bypass is reserved for younger and fitter patients or those undergoing ‘curative’ resection who are found to have disseminated disease. There is evidence that gastric bypass and coeliac ganglion blockade may reduce later vomiting and pain, with no added risk. Palliative chemoradiotherapy/chemotherapy offers little survival benefit, though gemcitabine may be associated with improved quality of life.
carcinoma. Adjuvant therapy is required to improve these figures, but there remains no consensus regarding such treatment. The recent European multi-centre ESPAC study suggested a role for chemotherapy (5-fluorouracil based) only (Neoptolemos et al.), but the study design was criticized. Poor prognostic factors are greater blood loss and transfusion requirements, lymph node metastases, positive resection margins, perineural and vascular invasion, tumour size (> 3 cm) and high tumour grade. Physiology – quality of life after PPPP is generally good. Diet can be normal, but pancreatic malabsorption often requires enzyme supplementation. Diabetes is a relatively rare complication of the procedure.
The future Surgical resection remains the mainstay treatment for periampullary cancer. It improves the otherwise poor prognosis (6–9 months), but is palliative in most cases. Other than earlier diagnosis, adjuvant strategies, new chemotherapeutic agents and possibly genetic manipulative therapies seem to offer the only means of improving the outcome. u REFERENCES Isla A M, Worthington T, Kakkar A K et al. A Continuing Role for Surgical Bypass in the Palliative Treatment of Pancreatic Carcinoma. Dig Surg 2000; 17: 143–6. Neoptolemos J P, Dunn J A, Stocken D D et al. Adjuvant Chemoradiotherapy and Chemotherapy in Resectable Pancreatic Cancer: A Randomised Controlled Trial. Lancet 2001; 358: 1576–85. Neoptolemos J P, Russell R C, Bramhall S et al. Low Mortality following Resection for Pancreatic and Periampullary Tumours in 1026 Patients: UK Survey of Specialist Pancreatic Units. UK Pancreatic Cancer Group. Br J Surg 1997; 84(10): 1370–6. Sohn T A, Yeo C J, Cameron J L et al. Resected Adenocarcinoma of the Pancreas – 616 Patients: Results, Outcomes, and Prognostic Indicators. J Gastrointest Surg 2000; 4(6): 567–79. Sohn T A, Yeo C J, Cameron J L et al. Do Preoperative Biliary Stents increase Postpancreaticoduodenectomy Complications? J Gastrointest Surg 2000; 4(3): 258–67 and 267–8.
Outcome Surgery – the outcome of surgical resection depends on the experience of the surgeon and therefore on volume of work. Guidelines suggest a minimum pancreatic resection rate of ten per year; centralization of pancreatic cancer services will help achieve this aim. Perioperative mortality has decreased from 25–30% to 1.8% (UK pancreatic centres 6%) (Neoptolemos et al., Sohn et al.), but the morbidity related to abdominal collections, leaking anastomoses and poor gastric function is about 40%. Assessment of co-morbidities is therefore essential and may preclude resection in an otherwise favourable case. Survival – current 5-year survival rates after resection are 5–10% for pancreatic cancer, 50% for ampullary cancer, 40–60% for primary duodenal cancer and 20–30% for distal cholangio-
MEDICINE
127
© 2003 The Medicine Publishing Company Ltd
What’s new
Periampullary Cancer
• Endoscopic ultrasonography is useful for detecting small pancreatic lesions when resection equates with cure • Portal vein resection is safe, but its long-term benefit remains unclear • Recent studies suggest that extended lymphadenectomy is of little value
Rob Hutchins R C N Williamson
Epidemiology and aetiology
useful in borderline cases (Figure 1). The latest multi-slice scanners may further improve assessment. • ‘Single-stop’ MRI and magnetic resonance cholangiopancreatography have not been shown unequivocally to be superior to CT. • Most surgeons would not advise percutaneous tissue biopsy diagnosis preoperatively, because of the risk of tumour seeding and the high detection rate of cancers in the presence of pancreatic and biliary strictures. The role of linear probe endoscopic ultrasound-guided biopsy has not been defined. • Staging laparoscopy with or without laparoscopic ultrasonography may reduce unnecessary laparotomies. However, it is probably of cost and patient benefit only in selected cases (pancreatic head and body cancers, not ampullary lesions).
The periampullary cancers comprise duodenal, ampullary and distal bile duct cancers; the most common is ductal carcinoma of the pancreas, which has a prevalence of 10/100,000 population. The incidence of distal bile duct cancers is increasing. Smoking, diabetes mellitus, chronic pancreatitis, male gender, greater age, hereditary pancreatitis and familial cancer syndromes predispose to pancreatic cancer. Duodenal cancer may arise from the polyps found in familial adenomatous polyposis. Ampullary cancers generally arise from pre-existing adenomas, and bile duct cancers are associated with primary sclerosing cholangitis, ulcerative colitis, papillomatosis, choledochal cysts, and anomalous junction of the pancreatic and biliary ductal systems.
Clinical features Management
Obstructive jaundice is the most common presentation of periampullary cancer. There may be associated weight loss, anorexia, pain or cholangitis. Duodenal and ampullary cancers may present with anaemia secondary to gastrointestinal bleeding. Pancreatic cancers may also present with paraneoplastic syndromes.
Preoperative biliary stenting is commonly practised in the UK. It is performed because of delays in referral, limited time for investigation and theatre restrictions. There is little evidence that routine preoperative stenting is beneficial, but any suspicion of cholangitis demands urgent decompression of the bile duct (Sohn et al.). Stenting is usually undertaken by the endoscopic route or, if this fails, percutaneously by the transhepatic route. Surgical resection is the only potential cure. Almost all patients undergo pylorus-preserving proximal pancreaticoduodenectomy (PPPP, Figure 2). This operation is as adequate as a conventional Whipple’s resection (which includes distal gastrectomy), but some units continue to perform the older procedure routinely and others offer it selectively on the basis of tumour spread. There are now few indications for total pan-
Investigations • Ultrasonography identifies biliary obstruction and, more importantly, the level of obstruction. It can miss a pancreatic head mass, but shows advanced disease with liver metastases. • Endoscopic retrograde cholangiopancreatography demonstrates both pancreatic and biliary strictures, and enables diagnostic brush biliary cytology (only 50% sensitivity) and therapeutic plastic stenting to relieve jaundice. Investigation centres on local and regional staging. • Spiral CT using a pancreatic protocol shows relative tumour hypoperfusion, disease dissemination and vascular invasion. • Bone scintigraphy is unhelpful unless specific new bony pain is evident. • CT of the chest is not cost-effective compared with simple plain radiography. • Endoscopic ultrasonography may show venous involvement better than CT, but is less useful for arterial encasement. • As CT has improved, many centres have abandoned arteriography for the assessment of vascular invasion, but it remains
Rob Hutchins is Consultant General and Hepatopancreatobiliary Surgeon at the Royal London Hospital, London, UK.
1 CT scan showing a large pancreatic head mass encasing the superior mesenteric vein (contrast-enhanced vessel in the middle of the mass). The distended gallbladder and adjacent duodenal loop are clearly visible.
R C N Williamson is Consultant Surgeon at Hammersmith Hospital, London, UK, Professor of Surgery at Imperial College, London, and Dean of the Royal Society of Medicine.
MEDICINE
126
© 2003 The Medicine Publishing Company Ltd
PANCREAS
a
b
2a The line of division of the neck of the pancreas is seen between the silk (black) sutures from the superior mesenteric vein (below) to the portal vein (above). The common bile duct ready for division is slung with an orange tape and the transfixed gastroduodenal artery is held between forceps. b The resected specimen. (By courtesy of Dr R Hart, Toronto, Canada.)
createctomy. Portal vein/superior mesenteric vein involvement is generally regarded as unresectable. Portal venous resection and reconstruction can be achieved with a low mortality, but this procedure is not often performed; its value is undetermined because of scarce information on tumour size, histological venous invasion and long-term outcome. Extended lymphadenectomy, including coeliac, superior mesenteric and para-aortic nodes, can be performed by an expert with little additional morbidity, but evidence of long-term survival benefit is awaited. Palliation usually comprises biliary decompression and analgesia. Biliary stenting may have a lower peri-procedure mortality than surgical bypass, but further hospital admissions may be required for stent blockage. In specialized centres, surgical bypass can be achieved with little or no mortality (Isla et al.). Survival is similar with the two methods. Mesh metal stents may have a higher patency rate, which becomes more important as new chemotherapeutic agents are developed and survival is prolonged. Surgical bypass is reserved for younger and fitter patients or those undergoing ‘curative’ resection who are found to have disseminated disease. There is evidence that gastric bypass and coeliac ganglion blockade may reduce later vomiting and pain, with no added risk. Palliative chemoradiotherapy/chemotherapy offers little survival benefit, though gemcitabine may be associated with improved quality of life.
carcinoma. Adjuvant therapy is required to improve these figures, but there remains no consensus regarding such treatment. The recent European multi-centre ESPAC study suggested a role for chemotherapy (5-fluorouracil based) only (Neoptolemos et al.), but the study design was criticized. Poor prognostic factors are greater blood loss and transfusion requirements, lymph node metastases, positive resection margins, perineural and vascular invasion, tumour size (> 3 cm) and high tumour grade. Physiology – quality of life after PPPP is generally good. Diet can be normal, but pancreatic malabsorption often requires enzyme supplementation. Diabetes is a relatively rare complication of the procedure.
The future Surgical resection remains the mainstay treatment for periampullary cancer. It improves the otherwise poor prognosis (6–9 months), but is palliative in most cases. Other than earlier diagnosis, adjuvant strategies, new chemotherapeutic agents and possibly genetic manipulative therapies seem to offer the only means of improving the outcome. u REFERENCES Isla A M, Worthington T, Kakkar A K et al. A Continuing Role for Surgical Bypass in the Palliative Treatment of Pancreatic Carcinoma. Dig Surg 2000; 17: 143–6. Neoptolemos J P, Dunn J A, Stocken D D et al. Adjuvant Chemoradiotherapy and Chemotherapy in Resectable Pancreatic Cancer: A Randomised Controlled Trial. Lancet 2001; 358: 1576–85. Neoptolemos J P, Russell R C, Bramhall S et al. Low Mortality following Resection for Pancreatic and Periampullary Tumours in 1026 Patients: UK Survey of Specialist Pancreatic Units. UK Pancreatic Cancer Group. Br J Surg 1997; 84(10): 1370–6. Sohn T A, Yeo C J, Cameron J L et al. Resected Adenocarcinoma of the Pancreas – 616 Patients: Results, Outcomes, and Prognostic Indicators. J Gastrointest Surg 2000; 4(6): 567–79. Sohn T A, Yeo C J, Cameron J L et al. Do Preoperative Biliary Stents increase Postpancreaticoduodenectomy Complications? J Gastrointest Surg 2000; 4(3): 258–67 and 267–8.
Outcome Surgery – the outcome of surgical resection depends on the experience of the surgeon and therefore on volume of work. Guidelines suggest a minimum pancreatic resection rate of ten per year; centralization of pancreatic cancer services will help achieve this aim. Perioperative mortality has decreased from 25–30% to 1.8% (UK pancreatic centres 6%) (Neoptolemos et al., Sohn et al.), but the morbidity related to abdominal collections, leaking anastomoses and poor gastric function is about 40%. Assessment of co-morbidities is therefore essential and may preclude resection in an otherwise favourable case. Survival – current 5-year survival rates after resection are 5–10% for pancreatic cancer, 50% for ampullary cancer, 40–60% for primary duodenal cancer and 20–30% for distal cholangio-
MEDICINE
127
© 2003 The Medicine Publishing Company Ltd