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INVESTIGATION AND DIAGNOSIS OF PERIAMPULLARY TUMOURS

INVESTIGATION AND DIAGNOSIS OF PERIAMPULLARY TUMOURS. Andrew Barclay – Austin Health. PREAMBLE. Pancreatic cancer is the fifth leading cause of cancer deaths. It has a poor prognosis with a 5-year survival rate of 3%.

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INVESTIGATION AND DIAGNOSIS OF PERIAMPULLARY TUMOURS

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  1. INVESTIGATION AND DIAGNOSIS OF PERIAMPULLARY TUMOURS Andrew Barclay – Austin Health

  2. PREAMBLE • Pancreatic cancer is the fifth leading cause of cancer deaths. It has a poor prognosis with a 5-year survival rate of 3%. • 95% of pancreatic carcinomas derive from the exocrine portion and therefore considered as adenocarcinomas • Other tumours include islet cell tumours or lymphomas • 75% of pancreatic cancers are considered to be periampullary.(1) • Periampullary tumours may originate from the head of pancreas, ampullaof Vater (4%), or mucosa of duodenum or bile duct itself (cholangiocarcinoma). • Tend to present earlier (mass effect) and therefore are usually small (<3cm) making imaging difficult.

  3. DIAGNOSIS • Clinical and investigative • Symptoms of pancreatic cancer • Pain (over 70%): tends to be a dull epigastric pain (+/- back pain) which is worse in a supine position. Initially episodic and related with meals but later becomes severe and persistent. However more than 50% of patients with early pancreatic cancer have little or no pain.(2) • Weight loss: loss of 7 to 10kg within a few weeks. Often preceeds all other symptoms • Jaundice (75%): deep and progressive

  4. DIAGNOSIS • More infrequently patients will present with pancreatitis, portal hypertension, GI bleeding, new-onset diabetes, migratory thrombophlebitis, polyarthralgia, or subcutaneous fat necrosis. • Rarely: hypercalcemia, hypoglycaemia, carcinoid syndrome, ACTH and inappropriate ADH production • Risk factors: 5% chronic pancreatitis (26 fold - 4% risk over 20yrs(6) ), 30% smoking (2 fold), diabetes (2 fold)(5), 5-10% hereditary: hereditary pancreatitis (50 fold), MEN, HNPCC, VPL, FAP, Gardner syndrome

  5. DIAGNOSIS • Periampullary tumours however tend to present at an earlier stage with obstructive jaundice (70-80%) (11) and are therefore more likely to be resectable. • Physical examination: excoriations, jaundice, palpable gallbladder (50%). • Incidental finding on imaging modalities or upper endoscopy

  6. INVESTIGATIVE • LFT’s, CA 19-9 • transabdominal ultrasound • triple-phase constrast enhanced helical CT • MRI, MRCP, MRA • ERCP • selective angiography • PET scanning • endoscopic ultrasound • percutaneous fine-needle aspiration • staging laparoscopy and laparascopic ultrasound

  7. ISSUES • Is this cancer? • If the presumptive diagnosis is periampullary cancer, is it resectable or does it only require a palliative procedure? • Non-resectablity is determined by metastasis, vascular or extra-pancreatic spread. - more specifically no direct extension to the coeliac or superior mesenteric arteries and a patent SMV-portal vein confluence.

  8. Blood Tests • LFT’s/component of conjugated bilirubin – helpful in determining obstruction in jaundiced patients • CA 19-9 - most extensively studied - nonspecific (elevated in other gastrointestinal carcinomas) - elevated in benign conditions(3) - only useful as follow-up surveillance

  9. JAUNDICE • First line imaging includes transabdominal ultrasound or high resolution CT scanning • Both detect dilated intrahepatic and extrahepatic ducts confirming obstruction Ultrasound is an inexpensive and non-invasive tool. In regard to pancreatic cancer its strength is in diagnosing liver metastasis (1cm) and lymph node involvement. With the addition of colour doppler it can be 80% accurate in diagnosing vascular invasion.(7) However it remains highly operator dependant.

  10. ERCP • Endoscopic retrograde cholangio-pancreatography is usually the next step in evaluating jaundiced patients. • Both investigative and therapeutic • Considered sensitive with 90-97% of people with pancreatic cancer having a positive ERCP • Note the complications: technical failure (10-15%), pancreatitis, sepsis, perforation and bleeding • Ampullary and duodenal cancers can be visualised and samples taken - cytological brushings, FNA, biopsy - not conclusive in detecting malignancy with only 35-65% sensitivity reported in the literature.(7)(11)

  11. ERCP • Mucosal changes of cancer can be difficult to distinguish from the erythema and oedema secondary to a passed gallstone both on visualisation and on microscopy.

  12. ERCP • Kimchi NA et al. The contribution of endoscopy and biopsy to the diagnosis of periampullary tumours. Tel Aviv University • 928 patients referred to institute for ERCP • 26 patients ended up having a malignancy • Sensitivity - on appearance (90%), on biopsy (81%) • Specificity - on appearance (33%), on biopsy (50%)

  13. ERCP • Cholangiogram: in regard to cancer the cholangiogram can demonstrate mass lesions distal to endoscopic visualisation and may also demonstrate duct dilatation post obstruction • Pancreatogram - single, irregular abrupt stricture of the pancreatic duct - gradual occlusion of the main duct - alteration of side branches near the tumour such as fragmentation - displacement of the main pancreatic duct - irregularly pooled contrast (within necrotic tumour) - ‘double duct sign’ strictured CBD and pancreatic duct • Pancreatitis: irregular and tortuous with multiple stenosis Shemesh et al. The role of endoscopic retrograde cholangiopancreatography in differentiating pancreatic cancer with chronic pancreatitis. Retrospective study on 10 patients with cancer and pancreatitis and 45 patients with only pancreatitis – all ten easily distinguished on pancreatogram

  14. CT • CT (as with MRI) can be used for diagnosis and to assess tumour resectability • The addition of triple-phase contrast enhanced spiral CT has improved this imaging modality. Multislice CT also considerably improves the images obtained. It also allows more accurate examination of the SMA which has an oblique course. • It is used to assess the presence of a mass, extrapancreatic involvement, vascular involvement, lymph node involvement and liver metastasis. It detects resectability in 70-80% and its accuracy in determining vascular involvement has largely replaced visceral angiography.(12)

  15. Lentschig MG et al. The value of 3-phase spiral CT and magnetic resonance tomography in preoperative diagnosis of pancreatic carcinoma. Radiology 1996; 36: 406-412 • Prospective study on 28 patients (18 unresectable) • Sensitivity: unresectability 94% for both CT and MRI resectability 80% CT and 70% MRI vascular involvement 82% CT and 62% MRI Conclusion of the study was that both techniques had similar clinical value.

  16. Phoa SS et al. Spiral computed tomography for preoperative staging of potentially resectable carcinoma of the pancreatic head. Brit J Surgery 1999; 86:789-794 • Prospective study on 56 patients using spiral CT (5mm)

  17. Cantaalano C et al. Pancreatic Carcinoma: the role of high-resolution multislice spiral CT in the diagnosis and assessment of resectability. Eur Radiology 2003; 13:149-156 • Prospective study on 44 patients using 1mm intervals • Diagnosis (sens/spec/accuracy) 97% 80% 96% Unresectability (sens/spec/accuracy) 96% 86% 93%

  18. MRI • MRI is generally considered as equivalent to CT in assessing pancreatic cancer. • Drawbacks: expensive/metal implants • Sterner E et al. Imaging of pancreatic neoplams: comparison of MRI and CT. AJR Am J Roentgenol 1989; 152:487-491 - assessed 32 patients with pancreatic cancer using MRI and CT and found no clinical benefit (subjectively noted that MRI was slightly clearer)

  19. MRI • However MRI technology continues to improve and the addition of MRCP and MRA bringing a new dimension to this modality. • Trede M et al. Ultrafast magnetic resonance imaging improves the staging of pancreatic tumors. Annals of Surgery 1997; 226(4): 393-407 • 58 patients compared using an ‘all in one’ MRCP/MRI/MRA combination with CT, angiography, and transabdominal ultrasound. • Included both pancreatic (35 within the pancreatic head), distal CBD (2) and periampullary (9) cancers: note 8 patients were mananged non-operatively

  20. This particular study also showed that UMRI had superior accuracy in detecting vascular involvement (89%) than CT (79%) or angiography (68%).

  21. Angiography • Visceral angiography with selective arterial injection of the coeliac and superior mesenteric arteries with venous phase studies had been considered as the best in demonstrating vascular anatomy and tumour encasement or occlusion. • Dooley WC et al. Is preoperative angiography useful in patients with periampullary tumors? Ann Surgery 1990; 211:649-655 • Found that 77% of patients with normal vessels on angiography were resectable while those with major vessel occlusion were unresectable. • However it is invasive and with recent studies demonstrating the accuracy of CT and MRI in respect to vascular involvement and anatomy it is generally not considered essential.

  22. Murugiah Met al. The role of selective visceral angiography in the management of pancreatic and periampullary cancer. World J Surg 1993; 17:796-800 • Prospective study of 46 patients with pancreatic/ periampullary tumours (no evidence of disseminated disease on Ultrasound/CT) • Wrongly diagnosed hepatic metastasis (7/9) • False positive result of 15% (in detecting irresectability) • False negative result of 48% (in dectecting resectability) • Study concluded that angiography was poor in determining resectability.

  23. Endoscopic Ultrasound • High-frequency inducer placed in the gastric and duodenal lumen to image the pancreas. This method is claimed to be superior than other methods in determining resectability and local lymph node involvement. It is able to diagnose cancers of 5mm in size but has difficulty distinguishing between pancreatic cancer and pancreatitis. • While it does offer the possibility of FNA it obviously is unable to detect distant metastasis and does have difficulty determining tumour encasement of the SMA.(8)

  24. Current studies suggest a role in diagnosing small tumours. However it remains operator dependant. • Muller MF et al. Pancreatic tumors: evaluation with endoscopic US, CT, and MR imaging. Radiology 1994; 190:745-751 • 49 patients with suspected pancreatic cancer (16 of which were less than 3cm). EUS had a superior accuracy of 94% compared to conventional CT (67%) and MRI (83%) in the diagnosis. • Midwinter MJ et al. Correlation between spiral computed tomography, endoscopic ultrasonography and findings at operation in pancreatic and ampullary tumours. British Journal of surgery 1999; 86:189-193 • 48 patients with 34 primary lesions found operatively. EUS diagnosed 33/34 while CT only found 26/34. In regard to determining vascular involvement both were equivalent except that EUS was less effective in diagnosing SMA involvement. Conclusion of the study was that EUS had a role in diagnosing small tumours.

  25. Percutaneous fine-needle aspiration • There are two disadvantages to this procedure. • It can produce seeding of the tumour(9) along the needle tract or intraperitoneally • The second consideration is that if an operation is planned anyway, a negative FNA will not alter management. • Its main benefit is to diagnose cancer in a patient who is not an operative candidate (for subsequent palliation) or diagnose a suspected pancreatic lymphoma. • Enayati PG et al. Traverso LW, Galagan K, et al. The meaning of equivocal pancreatic cytology in patients thought to have pancreatic cancer. Am J Surg. 1996;171:525-528. - retrospective study on 224 patients - 50% of those with atypical/non-malignant cytology had cancer

  26. Laparoscopy • None of the previous methods are accurately able to assess peritoneal and omental metastases which can be only 1 to 2mm size • 30% of liver metastasis are smaller than 2cm and may not be detected routinely(10). • Thus diagnostic laparoscopy can be performed in attempt to decrease the number of unnecessary laparotomies. The lesser sac and mesenteric root can also be explored. • However special expertise is required and there is a related morbidity rate of 2.5%(11). • Warshaw et al. Laparoscopy in the staging and planning for pancreatic cancer. Am J Surg 1986; 151:76-80 - 40 patients with known pancreatic cancer who were thought to be resectable. 14 out of 17 cases with intrabdominal metastasis were detected at diagnostic laparoscopy.

  27. Pisters PWT et al. Laparoscopy in the staging of pancreatic cancer. Brit J Surgery 2001; 88:325-337 • Review article examining the English literature (1996-2000) on staging laparoscopy commented that conclusions are difficult due to the inconsistent use of modern spiral CT. However it does conclude that routine use of laparoscopy (especially as a separate anaesthetic) is not appropriate given the available evidence. They suggest staging laparoscopy in those with larger tumours, equivocal radiological evidence of abdominal metastasis (including low-volume ascites), and changes in albumin and CA19-9.

  28. Brooks A et al. The Value of Laparoscopy in the Management on Non-Pancreatic Periampullary Tumors. (2001) • 139 patients examined with spiral CT • 127 patients having an adequate laparoscopy • 122 patients had malignancy • Diagnostic laparoscopy decreased the incidence of an unnecessary laparotomy by 8% (4 with liver metastasis, 4 with peritoneal seeding, 2 other) • Authors argued for selective use of diagnostic laparoscopy

  29. Laparoscopic Ultrasound • This technique improves the accuracy of staging laparoscopy in detecting local extension of tumour and liver metatasis. • John TG et al. Carcinoma of the pancreatic head and periampullary region.Tumor staging with laparoscopy and laparoscopic ultrasound. Ann Surg 1995; 221:156-164 • Prospective trial of 40 patients. Claims that the ultrasound component changed the decision regarding resectability in 10 patients (compared to laparoscopy alone). Note that pre-operative investigations included, ERCP transabdominal ultrasound and conventional CT.

  30. Pisters PWT et al. Laparoscopy in the staging of pancreatic cancer. Brit J Surgery 2001; 88:325-337 • This review article also examines the role of ultrasound at laparoscopy (1995-1998) and concludes that there is very little evidence comparing modern spiral CT (with defined limits of resectability) to the advantages gained by the addition of ultrasound. Although it concedes that ultrasound certainly improves the accuracy of laparoscopy.

  31. Peritoneal lavage and cytology during laparoscopy • Nieveen VD, Cytology of Peritoneal lavage performed during staging laparoscopy for gastrointestinal malignancies: is it useful? Annals of Surgery 1998; 228:728-733 • 449 patients: of the 28 patients who were cytology positive - 19 had metastasis at laparoscopy - 3 had false postive or misleading results - in 6 cases predicted irresectablitity (Therefore lacks any practical use)

  32. PET scanning • A review of the available literature(13) between 1994 and 1997 suggests PET scanning is good in diagnosing pancreatic cancer (accuracy 85-93%). • However there are few head to head trials with modern spiral CT, and therefore its role remains unclear in the diagnosis and staging of pancreatic carcinoma.

  33. Pancreatic head mass • Differentiating between chronic pancreatitis and pancreatic cancer can be difficult • Even intraoperative biopsy has a reported 10% false negative result • ERCP and PET scanning may be beneficial in diagnosis

  34. Bibliography • Keith D. et l. Current Management of Pancreatic Carcinoma. Annals of Surgery. 1995; 221:133-148 • Hudis C. et al. Pain is not a prominent symptom in most patients with early pancreas cancer. Proc Am Soc Clin Oncol 1991; 10:1149 note: retrospecitve study on 72 patients • Freboug W. et al. The evaluation of CA 19-9 antigen level in the early detection of pancreatic cancer. Cancer 1988; 62:2287-2290 note: 112 out of 866 patients with benign disease had elevated CA 19-9 • Shemesh E et al. The role of endoscopic retrograde cholangiopancreatography in differentiating pancreatic cancer with chronic pancreatitis. Cancer 1990; 65:893-896 • Everhart J et al.Diabetes mellitus as a risk factor for pancreatic cancer. Ameta- analysis. JAMA 1995; 273(20): 1605-9 • Lowenfels AB et al.Pancreatitis and the risk of pancreatic cancer. International Pancreatitis Study Group. N Engl J1993; 328(20): 1433-7 note: multicentre trial of 2000 patients • Cipolletta L et al. Pancreatic Head Mass: What can be done? JOP 2000; 1:108-110

  35. Tomiyama Tet al. Assessment of arterial invasion inpancreatic cancer using color Doppler ultrasonography. Am J Gastroenterol 1996; 91:1410-1416 • Trede M et al. Ultrafast magnetic resonance imaging improves the staging of pancreatic tumors. Annals of Surgery 1997; 226(4): 393-407 • Rashleigh-Bilcher HJC et al. Cutaneous seeding of pancreatic carcinoma by fine-needle aspiration biopsy. Brit J Radiol 1986; 59:182-183 • Ward EM et al. Computed tomographic characteristics of pancreatic carcinoma: An analysis of 100 cases. Radiographics 1983; 3:547-565 • John TG, Greig JD, Carter DC, Garden OJ. Carcinoma of the pancreatic head and periampullary region. Ann Surg 1995; 221:156-164 note: 40 patients in prospective study • Boris WK et al. Treatment of Resectable and Locally Advanced Pancreatic Cancer. Cancer Control: Journal of the Moffitt cancer centre 2000; 7:428-436 • Berberat P et al.Diagnosis and Staging of pancreatic Cancer by Positron Emission Tomography. World J Surgery 1999; 23:882-887

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