Recent developments in diagnosis of pancreatic cancer
http://www.100md.com
《英国医生杂志》
1 Section of Surgery, University Hospital, Queen's Medical Centre, Nottingham NG7 2UH, 2 Department of Radiology, University Hospital, Queen's Medical Centre, Nottingham
Correspondence to: D N Lobo dileep.lobo@nottingham.ac.uk
Introduction
We did an internet based search of the Medline and Science Citation Index databases by using the keywords "pancreatic cancer," "diagnosis," and "pancreatic imaging." We included reviews and evidence based studies in major journals from surgery, gastroenterology, and radiology published from January 1999 to June 2004, as well as key early papers.
Symptoms and signs
The laboratory findings in patients with pancreatic cancer are usually non-specific. Anaemia and hypoalbuminaemia may reflect the chronic nature of the neoplastic process and its nutritional sequelae. Patients presenting with obstructive jaundice show increases in serum bilirubin, alkaline phosphatase, and glutamyl transferase. Disproportionate increase of the transaminases may be associated with extensive liver metastases. Prolongation of prothrombin time results from exclusion of bile from the gastrointestinal tract leading to malabsorption of fat soluble vitamin K and decreased hepatic production of vitamin K dependent clotting factors. Glucose tolerance is also impaired in many patients; published evidence points to as many as 70% of patients with diagnosed pancreatic cancer having frank diabetes or impaired glucose tolerance.w3
Box 2: Signs and symptoms of pancreatic cancer
Symptoms
Jaundice
Weight loss
Nausea
Vomiting
Abdominal pain (late)
Anorexia
Diarrhoea
Signs
Jaundice
Palpable liver
Palpable gall bladder (Courvoisier's sign)
Abdominal tenderness
Ascites
Thrombophlebitis
Serological markers
Considerable improvements in non-invasive cross sectional radiological imaging in the past decade have greatly enhanced the ability to diagnose pancreatic cancer and plan appropriate treatment for patients. Accurate radiological staging of the disease allows for appropriate clinical decision making and ensures that surgery is limited to those patients who will benefit. "Diagnostic" laparotomy is now rarely undertaken, except as the final arbiter in cases of equivocal resectability.
Ultrasonography
Transabdominal ultrasonography is usually the initial screening investigation in patients presenting with jaundice. It can provide information, non-invasively, about the size, site, and characteristics of the primary tumour, the diameters of the biliary and pancreatic ducts, and the site of the obstruction. The presence or absence of lymph nodes or hepatic metastatic disease and the proximity of tumour to major vessels can also be determined.9 w5 Ultrasonography may even be as sensitive and specific as computed tomography in identifying hepatic metastases. The use of Doppler ultrasonography gives a reasonably reliable measure of vascular patency and can improve accuracy in measuring vascular invasion.9 The technique, however, is not without its limitations. Accurately assessing the pancreas, the size of the mass, and the extent of spread can often be difficult. The frequency of identification of the cancer by ultrasonography varies from 57% to 81%.10 w5 Ultrasonography is operator dependent and may be inaccurate more than one third of the time as a result of factors such as large body habitus, presence of ascites, or overlying bowel gas (in as many as 20% of patients10).
More recently, the use of echo enhanced power Doppler sonography (power Doppler sonography after injection of a contrast agent) has increased the sensitivity (to 87%) and specificity (to 94%) of this diagnostic modality.11 Coded phase inversion harmonic ultrasonography is another new technique that enables real time visualisation of slow flow in minute vessels in tumours with the use of a sonographic contrast agent and has been shown to have a sensitivity of 95% in detecting pancreatic tumours < 2 cm in diameter.12 These techniques are not freely available at present but may have an important role in aiding the diagnosis of pancreatic cancer in the future.
Computed tomography
Although transabdominal ultrasonography is often the first imaging modality used, the current method of choice for diagnosis and staging of pancreatic cancer is thin section (3-5 mm cuts), contrast enhanced, dual phase multidetector computed tomography (fig 1).8 13 14 Computed tomography provides better tumour definition than does ultrasonography, although small hepatic or periportal metastases may still be missed.
Fig 1 Contrast enhanced abdominal computed tomography scan showing (A) a large mass in the head of pancreas with encasement of the superior mesenteric artery (white arrow) and (B) dilated intrahepatic ducts (black arrowheads) and encasement of the superior mesenteric vein (white arrow)
Current computed tomography criteria for unresectability include the presence of metastatic disease (for example, liver, peritoneum), invasion of adjacent organs such as the stomach or colon, and encasement or occlusion of the peripancreatic vasculature. Encasement of the portal vein alone may not indicate inoperability as it may be resected with the tumour and then reconstructed. With these criteria, computed tomography has been shown to be almost 100% accurate in predicting unresectable disease.w9 However, the positive predictive value of the test is low, and approximately 25-50% of patients predicted to have resectable disease on computed tomography turn out to have unresectable lesions at laparotomy.11 The identification by preoperative imaging of patients who would not benefit from surgical exploration remains a challenge. The most common causes of unresectability are small peritoneal or liver tumour metastases (< 1 cm) and vascular involvement by the tumour.9 The advent of the multidetector dual phase computed tomography, along with three dimensional image reconstruction, has helped in improving the preoperative determination of surgical resectability, particularly in relation to vascular invasion.
Magnetic resonance imaging
Magnetic resonance imaging has recently been increasingly used in the evaluation of pancreatic tumours, although with the introduction of multidetector computed tomography the value of magnetic resonance imaging may be questionable.15 A study comparing magnetic resonance imaging and computed tomography in the imaging of pancreatic neoplasms concluded that magnetic resonance imaging offers no significant diagnostic advantage over computed tomography.16 However, the anatomy of the biliary tree and pancreatic duct are shown better with magnetic resonance cholangiopancreatography than with computed tomography. Magnetic resonance cholangiopancreatography has been shown to be as sensitive as endoscopic retrograde cholangiopancreatography in detecting pancreatic carcinomas.17 The resolution of magnetic resonance images of pancreatic pathology can be improved by using intravenous gadolinium enhancement. Pancreatic masses, biliary or pancreatic duct dilatation, and hepatic metastases can be shown in great detail.9 13 Additionally, contrast enhanced magnetic resonance angiography or venography can show vascular involvement with the tumour and obviate the need for conventional angiography.
Endoscopic retrograde cholangiopancreatography and percutaneous transhepatic cholangiography
Before the widespread availability of endoscopic retrograde cholangiopancreatography, percutaneous transhepatic cholangiography was often used to delineate the biliary anatomy preoperatively (fig 2). Endoscopic retrograde cholangiopancreatography has largely replaced percutaneous transhepatic cholangiography as it has several major advantages. Preoperative duct delineation is usually necessary to confirm the exact site of obstruction, exclude concurrent pathology, and exclude obstruction at multiple levels.w10
Fig 2 Percutaneous transhepatic cholangiogram showing a catheter in a dilated common bile duct with an abrupt, irregular stricture at the lower end, indicative of a pancreatic cancer
Endoscopic retrograde cholangiopancreatography, when used appropriately, can provide a definitive diagnosis. This is important, as only a third of tumours less than 2 cm and half of tumours less than 3 cm will be detected by conventional computed tomography.18 The advantages of endoscopic retrograde cholangiopancreatography over percutaneous transhepatic cholangiography are that it avoids liver puncture with the accompanying risk of bile leakage and haemorrhage and allows exclusion of other gastroduodenal disease, diagnosis of periampullary tumours, and imaging of the pancreatic duct. Brushing and biopsy specimens can also obtained for cytological and histological examination.
Both endoscopic retrograde cholangiopancreatography and percutaneous transhepatic cholangiography allow the insertion of biliary stents, and when access is difficult a combined approach may be necessary. However, preoperative biliary stenting has been embroiled in controversy. Sewnath et al suggested that it did not offer any benefit and should not be routinely carried out.19 Stenting provides ideal palliation for patients with jaundice who have unresectable or metastatic disease or are not fit for surgical resection. Expandable metal stents offer excellent palliation.w10 On the basis of current evidence, endoscopic retrograde cholangiopancreatography or percutaneous transhepatic cholangiography with stenting should not be used routinely in patients with resectable tumours as it may increase the rate of septic postoperative complications.19 Pragmatically, stenting may be necessary if surgery is not anticipated for several weeks or if the serum bilirubin concentration is rising rapidly.
Endoscopic ultrasonography
Endoscopic ultrasonography (fig 3) is a relatively new technique that is used to produce high resolution images of the pancreas by allowing the placement of a high frequency ultrasound probe in the stomach and duodenum in close proximity to the pancreas. Endoscopic ultrasonography may be the most accurate test for the diagnosis of pancreatic cancer. Studies comparing it with computed tomography have shown that endoscopic ultrasonography has a higher sensitivity and specificity for this diagnosis, particularly in evaluating tumours < 3 cm in diameter.20 In addition, endoscopic ultrasonography is highly accurate for detecting local invasion and nodal metastases from pancreatic cancer, although results are similar when compared with dual phase multislice multidetector computed tomography. Computed tomography does provide additional information about hepatic metastases.21 The side viewing duodenoscope that delivers the ultrasound probe also permits the detection of ampullary and duodenal carcinomas. However, the shortage of equipment, finances (an estimated ￡4.2 ($7.5; 6.2) million is needed to provide this facility nationwide22), and adequately trained endoscopists means that most patients in the United Kingdom do not have endoscopic ultrasonography.
Fig 3 Endoscopic ultrasound image showing mass in the head of pancreas in relation to adjacent structures (CBD=common bile duct; HA=hepatic artery; PV=portal vein; CA=coeliac axis)
Angiography
In the past, preoperative angiography was commonly used to predict resectability and to give information on vascular anatomy. Some studies have shown that angiography adds to the reliability of computed tomography, whereas other studies have shown that multidetector computed tomography can predict unresectability better than angiography alone.14 Conventional angiography is not currently part of the diagnostic protocol in most centres.
Positron emission tomography
Positron emission tomography is a non-invasive imaging tool that provides metabolic rather than morphological information on tumours. This diagnostic method is based on greater use of glucose by tumour cells than by normal pancreatic parenchyma.w11 A radioactive glucose analogue termed fluorodeoxyglucose is administered intravenously, followed by detection by the scanner of uptake of fluorodeoxyglucose by the tumour. Malignant tissues will show a higher uptake of fluorodeoxyglucose than normal surrounding tissues. Positron emission tomography is useful in diagnosing small tumours (< 2 cm) and detecting extrapancreatic disease such as peritoneal or omental metastases.9 At present it is not routinely used in the diagnosis of pancreatic cancer because of the lack of anatomical detail. With the advent of combined positron emission tomography and computed tomography scanning, both anatomical and functional imaging can be obtained simultaneously.23 w12
Additional educational resources
Further reading
Li D, Xie K, Wolff R, Abbruzzese JL. Pancreatic cancer. Lancet 2004;363: 1049-57
Yeo TP, Hruban RH, Leach SD, Wilentz RE, Sohn TA, Kern SE, et al. Pancreatic cancer. Curr Probl Cancer 2002;26: 176-275
DiMagno EP, Reber HA, Tempero MA. AGA technical review on the epidemiology, diagnosis, and treatment of pancreatic ductal adenocarcinoma. Gastroenterology 1999;117: 1464-84
O'Reilly E, Kelvin JF, Harty JR, McCully J. 100 questions and answers about pancreatic cancer. Subbury, MA: Jones and Bartlett, 2003
Useful websites
Cancer Research UK (www.cancerhelp.org.uk/trials/trials/default.asp)—Provides information on current clinical trials in cancer treatment, including those involving pancreatic cancer
Doctor's Guide (free registration required) (www.docguide.com)—American website for clinicians.
Can be set up to provide the latest news, clinical trial information, and news on advances in basic sciences for a variety of medical and surgical conditions
The Pancreatic Duct (www.acor.org/pancreas/)—An interesting website set up by a patient with pancreatic cancer for people diagnosed as having the disease
Other tests
Pancreatic cancers are staged using the TNM (tumour, node, metastasis) classification. Accurate staging has a vital role in the management of pancreatic tumours now that non-operative palliative options are available. Computed tomography is widely used in the preoperative staging of pancreatic neoplasms. With recent advances in magnetic resonance imaging and endoscopic ultrasonography, the accuracy of preoperative staging has improved, especially with respect to local invasion and regional node involvement.
Conclusions
Quinn M, Babb P, Brock A, Kirby L, Jones J. Cancer trends in England and Wales 1950-1999. London: Office for National Statistics, 2001.
Jemal A, Murray T, Samuels A, Ghafoor A, Ward E, Thun MJ. Cancer statistics, 2003. CA Cancer J Clin 2003;53: 5-26.
Li D, Xie K, Wolff R, Abbruzzese JL. Pancreatic cancer. Lancet 2004;363: 1049-57.
DiMagno EP. Pancreatic cancer: clinical presentation, pitfalls and early clues. Ann Oncol 1999;10(suppl 4): 140-2.
Gullo L. Diabetes and the risk of pancreatic cancer. Ann Oncol 1999;10(suppl 4): 79-81.
Yeo TP, Hruban RH, Leach SD, Wilentz RE, Sohn TA, Kern SE, et al. Pancreatic cancer. Curr Probl Cancer 2002;26: 176-275.
Ozkan H, Kaya M, Cengiz A. Comparison of tumor marker CA 242 with CA 19-9 and carcinoembryonic antigen (CEA) in pancreatic cancer. Hepatogastroenterology 2003;50: 1669-74.
Tamm EP, Silverman PM, Charnsangavej C, Evans DB. Diagnosis, staging, and surveillance of pancreatic cancer. AJR Am J Roentgenol 2003;180: 1311-23.
Clarke DL, Thomson SR, Madiba TE, Sanyika C. Preoperative imaging of pancreatic cancer: a management-oriented approach. J Am Coll Surg 2003;196: 119-29.
Potter MW, Shah SA, McEnaney P, Chari RS, Callery MP. A critical appraisal of laparoscopic staging in hepatobiliary and pancreatic malignancy. Surg Oncol 2000;9: 103-10.
Rickes S, Unkrodt K, Neye H, Ocran KW, Wermke W. Differentiation of pancreatic tumours by conventional ultrasound, unenhanced and echo-enhanced power Doppler sonography. Scand J Gastroenterol 2002;37: 1313-20.
Kitano M, Kudo M, Maekawa K, Suetomi Y, Sakamoto H, Fukuta N, et al. Dynamic imaging of pancreatic diseases by contrast enhanced coded phase inversion harmonic ultrasonography. Gut 2004;53: 854-9.
Kalra MK, Maher MM, Mueller PR, Saini S. State-of-the-art imaging of pancreatic neoplasms. Br J Radiol 2003;76: 857-65.
Vargas R, Nino-Murcia M, Trueblood W, Jeffrey RB Jr. MDCT in pancreatic adenocarcinoma: prediction of vascular invasion and resectability using a multiphasic technique with curved planar reformations. AJR Am J Roentgenol 2004;182: 419-25.
Hanbidge AE. Cancer of the pancreas: the best image for early detection—CT, MRI, PET or US? Can J Gastroenterol 2002;16: 101-5.
Steiner E, Stark DD, Hahn PF, Saini S, Simeone JF, Mueller PR, et al. Imaging of pancreatic neoplasms: comparison of MR and CT. AJR Am J Roentgenol 1989;152: 487-91.
Adamek HE, Albert J, Breer H, Weitz M, Schilling D, Riemann JF. Pancreatic cancer detection with magnetic resonance cholangiopancreatography and endoscopic retrograde cholangiopancreatography: a prospective controlled study. Lancet 2000;356: 190-3.
Graham RA, Bankoff M, Hediger R, Shaker HZ, Reinhold RB. Fine-needle aspiration biopsy of pancreatic ductal adenocarcinoma: loss of diagnostic accuracy with small tumors. J Surg Oncol 1994;55: 92-4.
Sewnath ME, Karsten TM, Prins MH, Rauws EJ, Obertop H, Gouma DJ. A meta-analysis on the efficacy of preoperative biliary drainage for tumors causing obstructive jaundice. Ann Surg 2002;236: 17-27.
Mertz HR, Sechopoulos P, Delbeke D, Leach SD. EUS, PET, and CT scanning for evaluation of pancreatic adenocarcinoma. Gastrointest Endosc 2000;52: 367-71.
Midwinter MJ, Beveridge CJ, Wilsdon JB, Bennett MK, Baudouin CJ, Charnley RM. Correlation between spiral computed tomography, endoscopic ultrasonography and findings at operation in pancreatic and ampullary tumours. Br J Surg 1999;86: 189-93.
National Cancer Guidance Group. Guidance on commissioning cancer services: improving outcomes in upper gastro-intestinal cancers: the manual. London: NHS Executive, 2001.
Hosten N, Lemke AJ, Wiedenmann B, Bohmig M, Rosewicz S. Combined imaging techniques for pancreatic cancer. Lancet 2000;356: 909-10.
Pisters PW, Lee JE, Vauthey JN, Charnsangavej C, Evans DB. Laparoscopy in the staging of pancreatic cancer. Br J Surg 2001;88: 325-37.(Arjun S Takhar, clinical )
Correspondence to: D N Lobo dileep.lobo@nottingham.ac.uk
Introduction
We did an internet based search of the Medline and Science Citation Index databases by using the keywords "pancreatic cancer," "diagnosis," and "pancreatic imaging." We included reviews and evidence based studies in major journals from surgery, gastroenterology, and radiology published from January 1999 to June 2004, as well as key early papers.
Symptoms and signs
The laboratory findings in patients with pancreatic cancer are usually non-specific. Anaemia and hypoalbuminaemia may reflect the chronic nature of the neoplastic process and its nutritional sequelae. Patients presenting with obstructive jaundice show increases in serum bilirubin, alkaline phosphatase, and glutamyl transferase. Disproportionate increase of the transaminases may be associated with extensive liver metastases. Prolongation of prothrombin time results from exclusion of bile from the gastrointestinal tract leading to malabsorption of fat soluble vitamin K and decreased hepatic production of vitamin K dependent clotting factors. Glucose tolerance is also impaired in many patients; published evidence points to as many as 70% of patients with diagnosed pancreatic cancer having frank diabetes or impaired glucose tolerance.w3
Box 2: Signs and symptoms of pancreatic cancer
Symptoms
Jaundice
Weight loss
Nausea
Vomiting
Abdominal pain (late)
Anorexia
Diarrhoea
Signs
Jaundice
Palpable liver
Palpable gall bladder (Courvoisier's sign)
Abdominal tenderness
Ascites
Thrombophlebitis
Serological markers
Considerable improvements in non-invasive cross sectional radiological imaging in the past decade have greatly enhanced the ability to diagnose pancreatic cancer and plan appropriate treatment for patients. Accurate radiological staging of the disease allows for appropriate clinical decision making and ensures that surgery is limited to those patients who will benefit. "Diagnostic" laparotomy is now rarely undertaken, except as the final arbiter in cases of equivocal resectability.
Ultrasonography
Transabdominal ultrasonography is usually the initial screening investigation in patients presenting with jaundice. It can provide information, non-invasively, about the size, site, and characteristics of the primary tumour, the diameters of the biliary and pancreatic ducts, and the site of the obstruction. The presence or absence of lymph nodes or hepatic metastatic disease and the proximity of tumour to major vessels can also be determined.9 w5 Ultrasonography may even be as sensitive and specific as computed tomography in identifying hepatic metastases. The use of Doppler ultrasonography gives a reasonably reliable measure of vascular patency and can improve accuracy in measuring vascular invasion.9 The technique, however, is not without its limitations. Accurately assessing the pancreas, the size of the mass, and the extent of spread can often be difficult. The frequency of identification of the cancer by ultrasonography varies from 57% to 81%.10 w5 Ultrasonography is operator dependent and may be inaccurate more than one third of the time as a result of factors such as large body habitus, presence of ascites, or overlying bowel gas (in as many as 20% of patients10).
More recently, the use of echo enhanced power Doppler sonography (power Doppler sonography after injection of a contrast agent) has increased the sensitivity (to 87%) and specificity (to 94%) of this diagnostic modality.11 Coded phase inversion harmonic ultrasonography is another new technique that enables real time visualisation of slow flow in minute vessels in tumours with the use of a sonographic contrast agent and has been shown to have a sensitivity of 95% in detecting pancreatic tumours < 2 cm in diameter.12 These techniques are not freely available at present but may have an important role in aiding the diagnosis of pancreatic cancer in the future.
Computed tomography
Although transabdominal ultrasonography is often the first imaging modality used, the current method of choice for diagnosis and staging of pancreatic cancer is thin section (3-5 mm cuts), contrast enhanced, dual phase multidetector computed tomography (fig 1).8 13 14 Computed tomography provides better tumour definition than does ultrasonography, although small hepatic or periportal metastases may still be missed.
Fig 1 Contrast enhanced abdominal computed tomography scan showing (A) a large mass in the head of pancreas with encasement of the superior mesenteric artery (white arrow) and (B) dilated intrahepatic ducts (black arrowheads) and encasement of the superior mesenteric vein (white arrow)
Current computed tomography criteria for unresectability include the presence of metastatic disease (for example, liver, peritoneum), invasion of adjacent organs such as the stomach or colon, and encasement or occlusion of the peripancreatic vasculature. Encasement of the portal vein alone may not indicate inoperability as it may be resected with the tumour and then reconstructed. With these criteria, computed tomography has been shown to be almost 100% accurate in predicting unresectable disease.w9 However, the positive predictive value of the test is low, and approximately 25-50% of patients predicted to have resectable disease on computed tomography turn out to have unresectable lesions at laparotomy.11 The identification by preoperative imaging of patients who would not benefit from surgical exploration remains a challenge. The most common causes of unresectability are small peritoneal or liver tumour metastases (< 1 cm) and vascular involvement by the tumour.9 The advent of the multidetector dual phase computed tomography, along with three dimensional image reconstruction, has helped in improving the preoperative determination of surgical resectability, particularly in relation to vascular invasion.
Magnetic resonance imaging
Magnetic resonance imaging has recently been increasingly used in the evaluation of pancreatic tumours, although with the introduction of multidetector computed tomography the value of magnetic resonance imaging may be questionable.15 A study comparing magnetic resonance imaging and computed tomography in the imaging of pancreatic neoplasms concluded that magnetic resonance imaging offers no significant diagnostic advantage over computed tomography.16 However, the anatomy of the biliary tree and pancreatic duct are shown better with magnetic resonance cholangiopancreatography than with computed tomography. Magnetic resonance cholangiopancreatography has been shown to be as sensitive as endoscopic retrograde cholangiopancreatography in detecting pancreatic carcinomas.17 The resolution of magnetic resonance images of pancreatic pathology can be improved by using intravenous gadolinium enhancement. Pancreatic masses, biliary or pancreatic duct dilatation, and hepatic metastases can be shown in great detail.9 13 Additionally, contrast enhanced magnetic resonance angiography or venography can show vascular involvement with the tumour and obviate the need for conventional angiography.
Endoscopic retrograde cholangiopancreatography and percutaneous transhepatic cholangiography
Before the widespread availability of endoscopic retrograde cholangiopancreatography, percutaneous transhepatic cholangiography was often used to delineate the biliary anatomy preoperatively (fig 2). Endoscopic retrograde cholangiopancreatography has largely replaced percutaneous transhepatic cholangiography as it has several major advantages. Preoperative duct delineation is usually necessary to confirm the exact site of obstruction, exclude concurrent pathology, and exclude obstruction at multiple levels.w10
Fig 2 Percutaneous transhepatic cholangiogram showing a catheter in a dilated common bile duct with an abrupt, irregular stricture at the lower end, indicative of a pancreatic cancer
Endoscopic retrograde cholangiopancreatography, when used appropriately, can provide a definitive diagnosis. This is important, as only a third of tumours less than 2 cm and half of tumours less than 3 cm will be detected by conventional computed tomography.18 The advantages of endoscopic retrograde cholangiopancreatography over percutaneous transhepatic cholangiography are that it avoids liver puncture with the accompanying risk of bile leakage and haemorrhage and allows exclusion of other gastroduodenal disease, diagnosis of periampullary tumours, and imaging of the pancreatic duct. Brushing and biopsy specimens can also obtained for cytological and histological examination.
Both endoscopic retrograde cholangiopancreatography and percutaneous transhepatic cholangiography allow the insertion of biliary stents, and when access is difficult a combined approach may be necessary. However, preoperative biliary stenting has been embroiled in controversy. Sewnath et al suggested that it did not offer any benefit and should not be routinely carried out.19 Stenting provides ideal palliation for patients with jaundice who have unresectable or metastatic disease or are not fit for surgical resection. Expandable metal stents offer excellent palliation.w10 On the basis of current evidence, endoscopic retrograde cholangiopancreatography or percutaneous transhepatic cholangiography with stenting should not be used routinely in patients with resectable tumours as it may increase the rate of septic postoperative complications.19 Pragmatically, stenting may be necessary if surgery is not anticipated for several weeks or if the serum bilirubin concentration is rising rapidly.
Endoscopic ultrasonography
Endoscopic ultrasonography (fig 3) is a relatively new technique that is used to produce high resolution images of the pancreas by allowing the placement of a high frequency ultrasound probe in the stomach and duodenum in close proximity to the pancreas. Endoscopic ultrasonography may be the most accurate test for the diagnosis of pancreatic cancer. Studies comparing it with computed tomography have shown that endoscopic ultrasonography has a higher sensitivity and specificity for this diagnosis, particularly in evaluating tumours < 3 cm in diameter.20 In addition, endoscopic ultrasonography is highly accurate for detecting local invasion and nodal metastases from pancreatic cancer, although results are similar when compared with dual phase multislice multidetector computed tomography. Computed tomography does provide additional information about hepatic metastases.21 The side viewing duodenoscope that delivers the ultrasound probe also permits the detection of ampullary and duodenal carcinomas. However, the shortage of equipment, finances (an estimated ￡4.2 ($7.5; 6.2) million is needed to provide this facility nationwide22), and adequately trained endoscopists means that most patients in the United Kingdom do not have endoscopic ultrasonography.
Fig 3 Endoscopic ultrasound image showing mass in the head of pancreas in relation to adjacent structures (CBD=common bile duct; HA=hepatic artery; PV=portal vein; CA=coeliac axis)
Angiography
In the past, preoperative angiography was commonly used to predict resectability and to give information on vascular anatomy. Some studies have shown that angiography adds to the reliability of computed tomography, whereas other studies have shown that multidetector computed tomography can predict unresectability better than angiography alone.14 Conventional angiography is not currently part of the diagnostic protocol in most centres.
Positron emission tomography
Positron emission tomography is a non-invasive imaging tool that provides metabolic rather than morphological information on tumours. This diagnostic method is based on greater use of glucose by tumour cells than by normal pancreatic parenchyma.w11 A radioactive glucose analogue termed fluorodeoxyglucose is administered intravenously, followed by detection by the scanner of uptake of fluorodeoxyglucose by the tumour. Malignant tissues will show a higher uptake of fluorodeoxyglucose than normal surrounding tissues. Positron emission tomography is useful in diagnosing small tumours (< 2 cm) and detecting extrapancreatic disease such as peritoneal or omental metastases.9 At present it is not routinely used in the diagnosis of pancreatic cancer because of the lack of anatomical detail. With the advent of combined positron emission tomography and computed tomography scanning, both anatomical and functional imaging can be obtained simultaneously.23 w12
Additional educational resources
Further reading
Li D, Xie K, Wolff R, Abbruzzese JL. Pancreatic cancer. Lancet 2004;363: 1049-57
Yeo TP, Hruban RH, Leach SD, Wilentz RE, Sohn TA, Kern SE, et al. Pancreatic cancer. Curr Probl Cancer 2002;26: 176-275
DiMagno EP, Reber HA, Tempero MA. AGA technical review on the epidemiology, diagnosis, and treatment of pancreatic ductal adenocarcinoma. Gastroenterology 1999;117: 1464-84
O'Reilly E, Kelvin JF, Harty JR, McCully J. 100 questions and answers about pancreatic cancer. Subbury, MA: Jones and Bartlett, 2003
Useful websites
Cancer Research UK (www.cancerhelp.org.uk/trials/trials/default.asp)—Provides information on current clinical trials in cancer treatment, including those involving pancreatic cancer
Doctor's Guide (free registration required) (www.docguide.com)—American website for clinicians.
Can be set up to provide the latest news, clinical trial information, and news on advances in basic sciences for a variety of medical and surgical conditions
The Pancreatic Duct (www.acor.org/pancreas/)—An interesting website set up by a patient with pancreatic cancer for people diagnosed as having the disease
Other tests
Pancreatic cancers are staged using the TNM (tumour, node, metastasis) classification. Accurate staging has a vital role in the management of pancreatic tumours now that non-operative palliative options are available. Computed tomography is widely used in the preoperative staging of pancreatic neoplasms. With recent advances in magnetic resonance imaging and endoscopic ultrasonography, the accuracy of preoperative staging has improved, especially with respect to local invasion and regional node involvement.
Conclusions
Quinn M, Babb P, Brock A, Kirby L, Jones J. Cancer trends in England and Wales 1950-1999. London: Office for National Statistics, 2001.
Jemal A, Murray T, Samuels A, Ghafoor A, Ward E, Thun MJ. Cancer statistics, 2003. CA Cancer J Clin 2003;53: 5-26.
Li D, Xie K, Wolff R, Abbruzzese JL. Pancreatic cancer. Lancet 2004;363: 1049-57.
DiMagno EP. Pancreatic cancer: clinical presentation, pitfalls and early clues. Ann Oncol 1999;10(suppl 4): 140-2.
Gullo L. Diabetes and the risk of pancreatic cancer. Ann Oncol 1999;10(suppl 4): 79-81.
Yeo TP, Hruban RH, Leach SD, Wilentz RE, Sohn TA, Kern SE, et al. Pancreatic cancer. Curr Probl Cancer 2002;26: 176-275.
Ozkan H, Kaya M, Cengiz A. Comparison of tumor marker CA 242 with CA 19-9 and carcinoembryonic antigen (CEA) in pancreatic cancer. Hepatogastroenterology 2003;50: 1669-74.
Tamm EP, Silverman PM, Charnsangavej C, Evans DB. Diagnosis, staging, and surveillance of pancreatic cancer. AJR Am J Roentgenol 2003;180: 1311-23.
Clarke DL, Thomson SR, Madiba TE, Sanyika C. Preoperative imaging of pancreatic cancer: a management-oriented approach. J Am Coll Surg 2003;196: 119-29.
Potter MW, Shah SA, McEnaney P, Chari RS, Callery MP. A critical appraisal of laparoscopic staging in hepatobiliary and pancreatic malignancy. Surg Oncol 2000;9: 103-10.
Rickes S, Unkrodt K, Neye H, Ocran KW, Wermke W. Differentiation of pancreatic tumours by conventional ultrasound, unenhanced and echo-enhanced power Doppler sonography. Scand J Gastroenterol 2002;37: 1313-20.
Kitano M, Kudo M, Maekawa K, Suetomi Y, Sakamoto H, Fukuta N, et al. Dynamic imaging of pancreatic diseases by contrast enhanced coded phase inversion harmonic ultrasonography. Gut 2004;53: 854-9.
Kalra MK, Maher MM, Mueller PR, Saini S. State-of-the-art imaging of pancreatic neoplasms. Br J Radiol 2003;76: 857-65.
Vargas R, Nino-Murcia M, Trueblood W, Jeffrey RB Jr. MDCT in pancreatic adenocarcinoma: prediction of vascular invasion and resectability using a multiphasic technique with curved planar reformations. AJR Am J Roentgenol 2004;182: 419-25.
Hanbidge AE. Cancer of the pancreas: the best image for early detection—CT, MRI, PET or US? Can J Gastroenterol 2002;16: 101-5.
Steiner E, Stark DD, Hahn PF, Saini S, Simeone JF, Mueller PR, et al. Imaging of pancreatic neoplasms: comparison of MR and CT. AJR Am J Roentgenol 1989;152: 487-91.
Adamek HE, Albert J, Breer H, Weitz M, Schilling D, Riemann JF. Pancreatic cancer detection with magnetic resonance cholangiopancreatography and endoscopic retrograde cholangiopancreatography: a prospective controlled study. Lancet 2000;356: 190-3.
Graham RA, Bankoff M, Hediger R, Shaker HZ, Reinhold RB. Fine-needle aspiration biopsy of pancreatic ductal adenocarcinoma: loss of diagnostic accuracy with small tumors. J Surg Oncol 1994;55: 92-4.
Sewnath ME, Karsten TM, Prins MH, Rauws EJ, Obertop H, Gouma DJ. A meta-analysis on the efficacy of preoperative biliary drainage for tumors causing obstructive jaundice. Ann Surg 2002;236: 17-27.
Mertz HR, Sechopoulos P, Delbeke D, Leach SD. EUS, PET, and CT scanning for evaluation of pancreatic adenocarcinoma. Gastrointest Endosc 2000;52: 367-71.
Midwinter MJ, Beveridge CJ, Wilsdon JB, Bennett MK, Baudouin CJ, Charnley RM. Correlation between spiral computed tomography, endoscopic ultrasonography and findings at operation in pancreatic and ampullary tumours. Br J Surg 1999;86: 189-93.
National Cancer Guidance Group. Guidance on commissioning cancer services: improving outcomes in upper gastro-intestinal cancers: the manual. London: NHS Executive, 2001.
Hosten N, Lemke AJ, Wiedenmann B, Bohmig M, Rosewicz S. Combined imaging techniques for pancreatic cancer. Lancet 2000;356: 909-10.
Pisters PW, Lee JE, Vauthey JN, Charnsangavej C, Evans DB. Laparoscopy in the staging of pancreatic cancer. Br J Surg 2001;88: 325-37.(Arjun S Takhar, clinical )