Büchler, Markus W.

Redaelli, Claudio A.

Schmied, Bruno M.

Z'graggen, Kaspar

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Problems in staging of pancreatic and hepatobiliary tumoursBruno M. Schmied, Kaspar Z'graggen, Claudio A. Redaelli and Markus W. BiichlerDepartment of Visceral and Transplantation Surgery, Inselspital, University of Bern, Bern, SwitzerlandIntroductionSurgery plays a key role in the therapy of hepatobil-iary and pancreatic cancer and 80-90% of patientsundergo surgery at least once. Although it is at presentthe only modality with a chance for long-term survival,curative surgery can be performed in only 40-50% ofpatients referred to specialised surgical institutions.Staging is an essential step in the management of pa-tients with hepatobiliary and pancreatic tumours. Pre-operative staging should ideally distinguish resectablefrom unresectable disease and sort out candidatesthat are best managed by palliative non-surgical treat-ment. Intraoperative staging determines resectabilityand the adequate surgical procedure for a specific pa-tient and finally postoperative and histopathologicalstaging (pTNM) may indicate the appropriate adju-vant therapy and should predict outcome.Metastatic and locally invasive hepatobiliary andpancreatic malignancy is, with a few exceptions, notamenable to resection and less so to curative surgery.Therefore the detection of tumour spread into distantorgans or locally into vessels is a crucial part of stag-ing procedures to determine resectability. So far, thisissue was often answered during explorative laparo-tomy but recent advances in radiological techniquesand diagnostic laparoscopy improved assessment oftumour extension before laparotomy. This article dis-cusses the problems in the preoperative staging anddetection of local invasion and metastases in hepato-biliary and pancreatic cancer.Preoperative stagingPercutaneous and endoscopic ultrasoundThe majority (70-90%) of patients with pancreaticor hepatobiliary carcinoma present with obstructivejaundice and ultrasonography (US) is often used asthe first imaging modality. The accuracy of US canexceed that of computed tomography (CT) and theapplication of endoscopic ultrasound (EUS) promisesfurther improvement for small lesions that are anatom-ically close to the stomach and the duodenum [1].In experienced hands, well-defined structures can betraced down to less than 10 mm [2]. US is an excel-lent technique to determine the level and aetiologyof a bile duct obstruction and provides informationabout the extension of an obstructive mass such as acholangiocarcinoma. In patients with hepatocellularcarcinoma (HCC) US is a reliable and routinely usedscreening tool and often allows the detection of soli-tary tumours without (Tl) and with invasion into thehepatic or portal veins (T2, T3) and multifocal lesions(T4). For surgical purposes we advocate an additiveuse in conjunction with CT.The main disadvantages of sonography are itsobserver dependency and its limitations in obese pa-tients. Moreover quality EUS is currently not avail-able in all institutions. Many surgeons have alsodifficulties creating virtual three dimensional imagesof tumour extension and prefer CT and/or MRI.Therefore, sonography is often used in screeningand for specific questions, such as the vicinity of atumour to portal veins in hilar cholangiocarcinoma.Vascular involvement (T4) of hepatobiliary cancercan be assessed by colour Doppler US with highaccuracy (91%) [3] and in combination with en-dosonography (ES) [4] infiltration of duodenum andperipancreatic tissue (T3) can be detected in pan-creatic cancer. Lymph node size is not a reliableindicator for the presence of metastasis and differen-tiation between reactive and malignant lymph nodesis notoriously difficult. Moreover the presence oflymph node metastasis does not change treatment orexclude a patient from potentially curative surgery[5]. Small liver (<3-5 mm) and peritoneal metas-tases may be missed by US in more than 15%.Computed tomography scan (CT)Progress of diagnostic imaging techniques especiallystandardisation of the spiral abdominal CT clearly161162 B.M. Schmied, K. Z'graggen, CA. RedaelliandM.W. Biichlerimproved tumour staging of pancreatic and hepato-biliary cancer and became the current gold standardfor preoperative staging [6]. Nevertheless, CT is of-ten used in combination with other techniques. Itsaccuracy to diagnose pancreatic cancer is more than90% [7] because benign non-cystic pancreatic tu-mours are rare. The distinction between malignancyand an inflammatory mass of the pancreatic head ina patient with chronic pancreatitis may be difficult[8]. In a recent study, it allowed to predict tumourresectability in 72% and its sensitivity and speci-ficity for irresectability was 78 and 76%, respectively[9,10]. Although its predictive value for vascular in-filtration was 88% in a recent publication [10], the ra-diological assessment of local tumour extension, e.g.the degree of vascular encasement and institutionalresectability rates are variable [11-13]. Tumours inthe head of the pancreas can also originate within theampullary tissue (papilla, distal common bile duct,duodenum) and these cancers represent different tu-mour biologies with a more favourable outcome. Theprognostic value of CT in these patients is thereforelimited.CT is capable to detect solitary, multifocal or dif-fusely infiltrating HCC. Small HCC (less than 1-2cm in diameter) can be difficult to diagnose usingdynamic intravenous-contrast enhanced CT with adetection rate of only 50-58% [14]. More advancedmodalities such as CT during arteriography or CTfollowing injection of Lipiodol may increase the di-agnostic accuracy for early HCC to 90-96% [14].Portal vein invasion in large HCC is demonstratedin up to 57% of cases using dynamic incrementalscanning [15] and invasion of hepatic veins is com-mon (T2-T4). The indication for surgery, however,is often not limited by the extension of HCC intothe hepatic vein, but rather by the presence of mul-tifocal tumours, infiltration of the portal pedicle ora reduced functional hepatic reserve in patients withliver cirrhosis [16].Endoscopic retrograde cholangiopancreatography(ERCP)Clinically jaundiced patients with hepatobiliary andpancreatic malignancies often undergo ERCP that al-lows definition of biliary pathology and alterations ofthe main pancreatic duct and its side branches withan accuracy of 95% [17]. ERCP is the gold standardin the detection of subtle pancreatic and biliary ab-normalities (Tis, Tl) but its value for tumour stagingis low [4]. The possibility to biopsy ductal pathol-ogy, collect samples for cytological analysis and toplace stents or nasobiliary drains to relief obstructivejaundice are often used in patients with hepatobiliaryand pancreatic malignancy. The physiologic changesinduced in a patient with obstructive jaundice have tobe included in the risk assessment. Although the useof preoperative biliary drainage is a controversy, weroutinely use endoscopic stent placement in patientswith cancer of the pancreatic head or extrahepaticbile duct tumours if bilirubin levels are > 100 n.mol/1[18].Magnetic resonance imaging and angiographyMagnetic Resonance Imaging (MR) including MRcholangiopancreaticography and MR-angiography[19] has the potential to replace CT in combina-tion with diagnostic ERCP as the primary stagingexamination. It allows in some patients the detec-tion of tumours smaller than 1 cm in diameter [20].However, since many hepatobiliary and pancreatictumours are not diagnosed in screening exams, thesensitivity for small non-symptomatic tumours isnot its main advantage. The ability of MR to de-fine tumour extension towards vascular structuresnon-invasively makes MR attractive for preopera-tive assessment. The reduction of cost and time ofexamination compared with CT will facilitate itsroutine application. MR-angiography also replacedconventional angiography, a technique that was reg-ularly used in many patients with hepatobiliary andpancreatic cancer.Diagnostic laparoscopySince all non-invasive staging examinations havea false negative rate of 10-30% for small liverand/or peritoneal metastases, diagnostic laparoscopyhas been advocated to avoid unnecessary laparotomyand/or to prove the malignant nature of hepatobiliaryand pancreatic tumours by biopsy. Its routine use hasbeen advocated for patients with pancreatic cancer,predominantly of the pancreatic body and tail. La-paroscopy can improve tumour staging but its valuefor the determination of resectability is questioned. Inpancreatic cancer detection of metastatic lesions by la-paroscopy has been reported in 10% to 35% [21-23].The value of concurrent peritoneal lavage cytologyand immunohistochemical examination that approx-imately doubles the detection of minimal peritonealtumour spread has not been defined conclusively. Weuse laparoscopy selectively in patients with locallyadvanced non-metastatic cancer because in more than75% of our pancreatic cancer patients laparoscopy didnot change course of treatment and allowed detectionof abdominal metastases in only 10%.Problems in staging of pancreatic and hepatobiliary tumours 163DiscussionA balanced preoperative assessment of patients withhepatobiliary and pancreatic tumours includes stag-ing of the malignancy but also registration of oper-ative risks, particularly pre-existing cardiopulmonarydisease to determine whether curative or palliativetreatment should be attempted. Potentially curativesurgery is defined by a radical resection (RO) ofthe primary tumour and may include, lymphadenec-tomy and in exceptional cases resection of mono- oroligotopic metastases. Since morbidity and mortalityrates decreased to a minimum in many centres, moreradical resections to improve long-term survival canbe performed [24-26]. While this approach signifi-cantly improved survival of patients with hepatobil-iary cancer [27], further studies on radical surgery inpancreatic cancer are planned and needed. Preopera-tive staging of tumours includes primarily radiologictechniques but analyses of functional reserve capac-ity of the affected organ, particularly the liver [16],molecular biological examinations of tumour-asso-ciated antigens, monoclonal antibodies, cytokines,genetic markers and the detection of minimal cancerspread in blood, bone marrow and the peritonealcavity are currently under investigation and may inthe future improve staging.New diagnostic tools have improved preoperativestaging and allow a more accurate definition of localtumour extension and further technical developmentscan be expected. When distant spread of cancer hasbeen excluded, surgical exploration is often indicatedsince resectability is defined intraoperatively and re-section is possible in many cancers of the liver,bile duct and the pancreas. Therefore, the importantinformation for the surgeon collected by the abovementioned studies, pertains to the presence of metas-tases and definitive signs of irresectability, such as acomplex infiltration of vascular structures [28].Advances in surgical technique such as the saferesection and reanastomosis of portal structures, mul-tivisceral resections, segmental liver resection withpreservation of functional hepatic capacity, have ex-tended the spectrum of surgical indications towardsmore advanced tumours. In addition to a considerablereduction of both, morbidity and mortality [24] thelong-term survival of hepatobiliary cancer after rad-ical surgery increased during recent years and evenfor ductal adenocarcinoma of the pancreas 5-yearsurvival of 15-30% are reported.We therefore conclude that although preoperativestaging certainly increased in accuracy, surgical ex-ploration and resection are still essential in patientswith hepatobiliary and pancreatic malignancies. Theaddition of biological markers and molecular stag-ing may improve ability to treat these patients morespecifically and at an earlier stage, and new treatmentmodalities may in the future allow to have effec-tive treatment of advanced stages and local tumourextension.References1 Brugge WR, Van Dam J. Pancreatic and biliary endoscopy. NEngl J Med 1999; 24: 1808-1816.2 Cosgrove D: Ultrasound in surgery of the liver and biliarytract. In: L Blumgart (ed). Surgery of the Liver and BiliaryTract Churchill Livingstone, London, 1994, pp 189-221.3 Smits NJ, Reeders JW. Imaging and staging of biliopancreaticmalignancy: role of ultrasound. Ann Oncol 1999; suppl 4:20-24.4 Tio TL, Wijers OB, Sars PR, et al. Preoperative TNM clas-sification of proximal extrahepatic bile duct carcinoma byendosonography. Semin Liver Dis 1990; 2: 114-120.5 Smits NJ, Reeders JW. Current applicability of duplexDoppler ultrasonography in pancreatic head and biliary ma-lignancies. Baillieres Clin Gastroenterol 1995; 1: 153-172.6 Bluemke DA, Fishman EK. CT and MR evaluation of pancre-atic cancer. Surg Oncol Clin N Am 1998; 1: 103-124.7 Baer H, Wagner M, Buchler M. Onkologische Standard-chirurgie des Pancreaskarzinoms. Chir Gastroenterol 1998;14: 42-48.8 Beger HG, Buchler M. Duodenum-preserving resection of thehead of the pancreas in chronic pancreatitis with inflammatorymass in the head. World J Surg 1990; 1: 83-87.9 Saldinger PF, Reilly M, Reynolds K, et al. Is CT angiogra-phy sufficient for prediction of resectability of periampullaryneoplasms? J Gastrointest Surg 2000; 4: 233-239.10 Phoa SS, Reeders JW, Rauws EA, et al. Spiral computedtomography for preoperative staging of potentially resemblecarcinoma of the pancreatic head. Br J Surg 1999; 6: 789-794.11 Gmeinwieser J, Feuerbach S, Hohenberger W, et al. Spiral-CTin diagnosis of vascular involvement in pancreatic cancer.Hepatogastroenterology 1995; 4:418-22.12 Warshaw AL, Gu ZY, Wittenberg J, et al. Preoperative stagingand assessment of resectability of pancreatic cancer. ArchSurg 1990; 2: 230-233.13 Hough TJ, Raptopoulos V, Siewert B, et al. Teardrop superiormesenteric vein: CT sign for unresectable carcinoma of thepancreas. AIR Am J Roentgenol 1999; 6: 1509-1512.14 De Santis M, Romagnoli R. MRI of small hepatocellularcarcinoma: comparison with US, CT, DSA, and lipidol-CT. JComput Assist Tomogr 1992; 189-197.15 Mathieu D, Grenier P, Larde D, et al. Portal vein involvementin hepatocellular carcinoma: dynamic CT features. Radiology1984; 1: 127-132.16 Zimmermann H, Reichen J: Hepatectomy: preoperative anal-ysis of hepatic function and postoperative liver failure. DigSurg 1998; 1: 1-11.17 Spinelli P, Schiavo M, Schicchi AA: [Endoscopy in the di-agnosis and staging of pancreatic cancer]. Tumori 1999; 1(suppl 1): S14-8.18 Z'graggen K, Kulli C, Holzinger F, et al. Operative Strategicbe periampullarem Karzinom und Dcterus. Chir Gastroenterol1999; 48-54.164 B.M. Schmied, K. Z'graggen, CA. RedaelliandM.W. Bitchier19 Trede M, Rumstadt B, Wendl K, et al. Ultrafast magneticresonance imaging improves the staging of pancreatic tumors.Ann Surg 1997; 4: 393-405; discussion 405-407.20 Me H, Honda H, Kaneko K, et al. Comparison of helical CTand MR imaging in detecting and staging small pancreaticadenocarcinoma. Abdom Imaging 1997; 4: 429-433.21 Fernandez-del Castillo C, Rattner DW, Warshaw AL. Furtherexperience with laparoscopy and peritoneal cytology in thestaging of pancreatic cancer. Br J Surg 1995; 8: 1127-1129.22 Friess H, Kleeff J, Silva JC, et al. The role of diagnosticlaparoscopy in pancreatic and periampullary malignancies. JAm Coll Surg 1998; 6: 675-682.23 Makary MA, Warshaw AL, Centeno BA, et al. Implications ofperitoneal cytology for pancreatic cancer management. ArchSurg 1998; 4: 361-365.24 Biichler M, Friess H, Wagner M, et al. Pancreatic fistula afterpancreatic head resection. Br J Surg 2000; in press.25 Yeo CJ, Abrams RA, Grochow LB, et al. Pancreaticoduo-denectomy for pancreatic adenocarcinoma: postoperative ad-juvant chemoradiation improves survival. A prospective, sin-gle- institution experience. Ann Surg 1997; 5: 621-33; dis-cussion 633-636.26 Conlon KC, Klimstra DS, Brennan MF. Long-term survivalafter curative resection for pancreatic ductal adenocarcinoma.Clinicopathologic analysis of 5-year survivors. Ann Surg1996; 3: 273-279.27 Bartlett DL, Fong Y, Former JG, et al. Long-term results afterresection for gallbladder cancer. Implications for staging andmanagement. Ann Surg 1996; 5: 639-646.28 McCarthy MJ, Evans J, Sagar G, et al. Prediction of re-sectability of pancreatic malignancy by computed tomogra-phy. Br J Surg 1998; 3: 320-325.

Pancreatic and hepatobiliary cancers: Problems in staging of pancreatic and hepatobiliary tumours

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