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Endoscopic retrograde cholangiopancreatography in pancreatic islet cell tumors
distance required for the endoscope to reach the ampulla precluded success (Fig. 1). Although not entirely an endoscopic procedure, the combined PEBS techniqueS is recommended as a backup for any unsuccessful endoscopic stent placement attempt. Based on our experience, we feel the PEBS technique is ideally suited to the patient with Billroth II gastrojejunostomy or Roux-en- Y enteroenterostomy. We strongly recommend this procedure as an alternative to palliative surgical bypass. It remains to be seen whether this method can be applied to other types of biliary obstruction, such as biliary duct bifurcation tumor, failure to endoscopically cannulate low common duct tumors, and those cases in which endoscopically placed guide wires cannot be passed from below due to tight stenoses. REFERENCES 1. Soehendra N, Reynders-Frederix V. Palliative bile duct drainage-a new endoscopic method of introducing a transpapillary drain. Endoscopy 1980;12:8-11.
2. Huibregtse K, Tytgat GN. Palliative treatment of obstructive jaundice by transpapillary introduction of large bore bile duct endoprosthesis: experience in 45 patients. GUT 1982;23:371-5. 3. Huibregtse K, Tytgat GNJ. Endoscopic placement of biliary prosthesis. In: Salmon PR, ed. Gastrointestinal endoscopyadvances in diagnosis and therapy, vol 1. Baltimore: Williams & Wilkins, 1984:219-31. 4. Brambs JH, Billmann P, Pausch J, Holslege A, Salm R. Nonsurgical biliary drainage: endoscopic conversion of percutaneous transhepatic into endoprosthetic drainage. Endoscopy 1986;18:52-4. 5. Hagenmuller F. Results of endoscopic bilioduodenal drainage in malignant bile duct stenosis. In: Classen M, Geenen J, Kawai K, eds. Nonsurgical biliary drainage. Berlin: Springer-Verlag, 1984:93-104. 6. Classen M, Hagenmuller F. Endoscopic biliary drainage. Scand J GastroenteroI1984;19(suppl 2):76-83. 7. Tytgat GNJ, Bartelsman JFWM, Den Hartog Jager FCA, Huibregtse K, Mathus-Vliegen EMH. Upper intestinal and biliary tract endoprosthesis. Dig Dis Sci 1986;31(9-Sep suppl):67S76S. 8. Tsang TK, Crampton AR, Bernstein JR, Ramos SR, Wieland JM. Percutaneous-endoscopic biliary stent placement: preliminary report. Ann Intern Med 1987;106:389-92. 9. Kerlan RK, Ring EJ, Pogany AC, Jeffrey RB. Biliary endoprosthesis insertion using a combined peroral-transhepatic method. Radiology 1984;150:828-30.
Case Reports Endoscopic retrograde cholangiopancreatography in pancreatic islet cell tumors Allen R. Kaufman, MD Michael V. Sivak, Jr., MD D. Roy Ferguson, MD
Endoscopic retrograde cholangiopancreatography (ERCP) is a well established technique in the evaluation of patients with suspected pancreatic disease. 1- 3 Specific signs of pancreatic disorders have been recognized as experience with this modality has increased. 4- 7 We report five cases of pancreatic islet cell tumors with pancreatographic findings that differ from those of pancreatic adenocarcinoma. CASE REPORTS Case 1
A 28-year-old white woman was referred to our institution and had a 2-month history of abdominal pain, 15-pound weight loss, and elevated serum amylase. There was no From the Department of Gastroenterology, Cleveland Clinic Foundation, Cleveland, Ohio. Reprint requests: Michael V. Sivak, Jr., MD, Department of Gastroenterology, Cleveland Clinic Foundation, 9500 Euclid Avenue, Cleveland, Ohio 44106. VOLUME 34, NO.1, 1988
history of alcohol abuse. Ultrasonography of the gallbladder was normal. ERCP revealed a dilated and irregular pancreatic duct that was thought to be consistent with chronic pancreatitis (Fig. 1). More than a year later the patient returned, having been hospitalized twice during the previous year for epigastric pain and diarrhea. At that time, she noted a 2-week history of worsening midepigastric pain, diarrhea, jaundice, and pruritis. Her weight had been stable for the past year. On laboratory evaluation the total bilirubin level was 10.0 mg/ 100 ml (normal, 0 to 1.4 mg/l00 ml), alkaline phosphatase level was 350 units/liter (normal, 20 to 110 units per liter), SGOT level was 103 units/liter (normal, 7 to 40 units/liter), and the serum amylase level was 158 units/liter (normal, 10 to 135 units/liter). Ultrasonography disclosed dilation of the intrahepatic and extrahepatic biliary ducts and enlargement of the head of the pancreas. ERCP also demonstrated common bile and intrahepatic duct dilation. There was also marked narrowing, effacement, and lateral displacement of the distal common bile duct (Fig. 2A). Moderate generalized dilation of the pancreatic duct was also present, and there was an area of stenosis in the retropapillary portion of the main pancreatic duct (Fig. 2B). An exploratory laparotomy was performed, and the patient underwent a Whipple procedure for a 3-cm metastatic islet cell tumor of the head ofthe pancreas. All of the four peripancreatic lymph nodes showed evidence of tumor. 47
Figure 1. Retrograde pancreatogram (patient 1) demonstrates a dilated, irregular pancreatic duct. The common bile duct is normal.
Case 2
This 45-year-old white man had a 6-month history of diarrhea with foul-smelling stools and an associated 40pound weight loss. A 72-hour stool fecal fat collection revealed 67 g of fat. A small bowel biopsy was normal. Computed tomography (CT) revealed a lobulated head of the pancreas but was otherwise normal. ERCP disclosed two persistent filling defects over the lateral aspect of the distal common bile duct (Fig. 3). There was an increased medial convexity of the distal common duct that was consistent with displacement. The pancreatic duct filled poorly with contrast material and was not visualized beyond the head. The visualized portion suggested dilation of the main pancreatic duct branches. A duodenal ulcer in the apex of the bulb was noted at ERCP. The patient underwent exploratory laparotomy at which a 3-cm tumor confined to the head of the pancreas was found. A Whipple procedure was performed. The pathologic specimen included an islet cell tumor of the pancreas that had extended into the duodenal wall with associated duodenal mucosal ulceration. Seven peripancreatic lymph nodes were all negative for malignancy. Case 3
A 53-year-old white man was referred and had a 3-month history of constipation, upper abdominal pain radiating to the back, and an associated 35-pound weight loss. Laboratory tests showed normal serum total bilirubin, amylase, and lipase, although the alkaline phosphatase level was 264 units/liter. CT demonstrated a mass involving the head of the pancreas. ERCP disclosed narrowing of the distal portion of the pancreatic duct with displacement and effacement of a branch to the uncinate process (Fig. 4). These findings were thought to suggest a mass lesion, but they were not considered definite. CT-guided needle aspiration biopsy of the pancreatic mass revealed abnormal cells consistent with a nonductal epithelial neoplasm of islet cell or carcinoid origin. 48
Figure 2. A, Second retrograde cholangiOgram in same patient as Figure 1 (patient 1) obtained 14 months later, demonstrating dilation of the common bile duct as well as narrowing, effacement, and lateral displacement of the distal common bile duct (arrow). B, Moderate generalized dilation of the pancreatic duct is shown along with stenosis of the duct in the retropapillary portion (arrows).
The patient underwent an exploratory laparotomy, and a large irregularly formed mass was found that arose from the pancreas and extended anteriorly. A cholecystojejunostomy was performed. Pathologic examination of the resected mass disclosed an islet cell carcinoma with involvement of gastrocolic and celiac nodes. The patient was treated with 5fluorouracil and chlorazotocin. Case 4
A 70-year-old white man was referred to our institution and had a 3-month history of lower abdominal pain, alternating diarrhea and constipation, and elevated serum amylase and lipase values. Previous ultrasonography of the gallbladder had been negative. There was no history of alcohol abuse. Four years earlier, the patient had undergone GASTROINTESTINAL ENDOSCOPY
Figure 3. Retrograde cholangiogram (patient 2) demonstrating displacement of distal lower common bile duet with persistent filling defects over the lateral aspect (arrows). The main pancreatic duct branches are dilated, although the pancreatic duct is not visualized beyond the portion in the head (curved arrow).
excision and drainage of the pancreatic pseudocyst. There was no evidence of tumor at laparotomy. Five months later the patient was rehospitalized and had recurrent abdominal pain, nausea, and elevated serum amylase level (2,500 units). CT of the abdomen showed a mass in the body and tail of the pancreas. The serum total bilirubin level was 1.0 mg/lOO ml and alkaline phosphatase was 1160 unitsfliter. ERCP disclosed relative narrowing of the pancreatic duct in the head with no filling of main pancreatic duct side branches (Fig. 5). The main duct in the body of the pancreas was markedly dilated, and there was no opacification of main-duct branches. Pancreatography in the region of the tail showed a constricted segment along with some dilated, sacculated, ectatic branch ducts. The patient underwent laparotomy with distal pancreatectomy for an islet cell tumor of the pancreatic tail, along with an end to end pancreaticojejunostomy and an end to side cholecystojejunostomy. The pancreatic islet cell tumor was histologically identical to the lung tumor that had been resected in 1974. Fourteen months later the patient was readmitted and had recurrent abdominal pain, nausea, and an associated 10-pound weight loss. The serum total bilirubin level was 0.6 mg/loo ml and alkaline phosphatase was 175 units/liter. CT of the abdomen showed no pancreatic mass. A repeat ERCP study showed distortion of the pancreatic duct in the head with marked medial displacement and narrowing (Fig. 6). A few of the main pancreatic duct branches in the head were dilated and ectatic. There was acute angulation of the main pancreatic duct in the region of the junction of the head and body. The duct in the body of the gland was dilated and showed no opacification of its branches. Contrast medium drained via the pancreaticojejunostomy. The overall appearance of the pancreatogram
Figure 4. Retrograde pancreatogram (patient 3) suggesting distal pancreatic duct narrowing with displacement and effacement of a branch to the uncinate process (arrow).
resection of the lower lobe of the left lung for a spindle-cell carcinoid tumor. Laboratory evaluation showed serum total bilirubin level of 3.4 mg/loo ml, alkaline phosphatase 350 units/liter, SGOT 85 units/liter, and amylase 988 units. CT revealed a large pseudocyst in the head of the pancreas. One week later the patient underwent exploratory laparotomy with partial VOLUME 34, NO.1, 1988
Figure 5. Retrograde pancreatogram (patient 4) demonstrating relative narrowing of the pancreatic duct in the head (short arrow), dilation of the duct in the body (long arrow), and a constricted area in the tail (curved arrow) with dilated sacculated and ectatic branches. There is no filling of main duct branches in the head or body. 49
Figure 6. Repeat retrograde pancreatogram (patient 4) 14
Figure 7. Retrograde pancreatogram (patient 5) showing
months after the pancreatogram in Figure 5, demonstrating medial displacement and narrowing of the main pancreatic duct in the head (short arrow) with dilated ectatic branches. The duct in the body is dilated with no opacification of side branches. Note the acute angulation at the junction of the head and body (long arrow). Contrast medium injected at the duodenal papilla drains via the pancreaticojejunostomy (curved arrow).
effacement and displacement of the main pancreatic duct in the head (small arrows). The duct in the body is dilated relative to the diameter of that in the head, and the side branches are dilated. The main duct in the head fills poorly, while the accessory duct (long arrow) fills readily. Effacement of opacified acinar tissue (wide arrow) is noted near the medial wall of the descending duodenum.
suggested displacement of the main pancreatic duct by a mass. The patient was treated conservatively with bilateral celiac plexus blocks for control of pain. Chemotherapy was refused.
the main pancreatic duct or its branches. The reported sensitivity of ERCP in the recognition of pancreatic adenocarcinoma has been in excess of 90% in most series. 7- 15 There are several characteristic pancreatographic findings: an abrupt or gradual occlusion of the main duct; stenosis of the main duct with or without prestenotic ectasia; and changes in the main duct branches, such as fragmentation and cystic destruction; displacement of ductules; and pooling of contrast material in irregular pockets of a necrotic tumor mass. 12 In addition, stenosis of the common bile duct with an irregular shouldering may be noted. It is well recognized that chronic pancreatitis can produce similar ductal changes. 9 ,12 Stricture or obstruction of both the bile duct and pancreatic duct at the same level, the double duct sign, is a very reliable sign of pancreatic malignancy, although this finding is not pathogonomic of carcinoma since similar findings are noted in chronic pancreatitis. 4 , 9,16 Specific ductal characteristics suggestive of malignancy include ductal obstruction, especially of the common bile duct, close proximity of the biductallesions, a short stenotic segment of the common bile duct removed from the papilla, and an abrupt irregular transition from normal to stenotic or obstructed duct. 4 ,17-19 Pancreatic islet cell carcinoma was first reported by Fabozzi in 1903. 20 Islet cell tumors are rare, with a prevalence estimated at less than 1/100,000 of the population. 21 In one large series of islet cell tumors 60% were insulinomas, 18% gastrinomas, and 15%
Case 5
A 59-year-old black woman was referred and had a 4month history of epigastric pain. She had no history of alcohol abuse or of gallstones. Previous ultrasonography and CT of the abdomen had been interpreted as showing a pseudocyst of the head of the pancreas. ERCP showed effacement of the main pancreatic duct in the head of the pancreas (Fig. 7). The main duct in the region of the head filled poorly with contrast material. The accessory duct, however, was readily opacified. There was opacification of the pancreatic ductal system to the acinar level in the head of the pancreas, and acinar filling was noted as a faint blush along the duodenal wall. The main pancreatic duct was dilated in the body relative to the diameter of the duct in the head, and the main duct branches in this portion were also dilated. The overall appearance of the pancreatogram suggested a mass in the head of the pancreas that was displacing normal ductal and acinar tissues. The patient underwent exploratory laparotomy and excision of a lO-cm islet cell tumor of the head of the pancreas. DISCUSSION
Most pancreatic malignancies are adenocarcinomas that arise in the ductal system, so that even small lesions will usually produce stenosis or occlusion of 50
GASTROINTESTINAL ENDOSCOPY
nonfunctioning. 22 Islet cell tumors, in contrast to ductal carcinomas of the pancreas, are generally slow growing, and the presence of metastases does not exclude prolonged survival,22.23 Kent et al. 22 reported 3- and 5-year survival rates of 60% and 44%, respectively, for pancreatic islet cell tumors. Nonfunctioning islet cell tumors are more amenable to treatment than pancreatic adenocarcinoma. An aggressive surgical approach has generally been recommended. Kent et al. 22 have reported survival as long as 12 and 26 years after Whipple procedure for this tumor. Survival after biliary bypass procedures in patients with liver metastases may also be prolonged relative to that for patients with metastatic pancreatic adenocarcinoma. Chemotherapy is much more likely to be of benefit in patients with islet cell carcinoma; response rates of over 60% have been reported with combined streptozocin and 5-fluorouracil therapy.24 The clinical presentation of nonfuctioning islet cell tumors is nonspecific. In one series of 25 such patients, the most frequent presenting complaints were pain (36%) and jaundice (28%) due to the mass effect of the tumor and invasion of surrounding structures. 22 Ascites (4%), a palpable mass (8%), confusion (4%), and steatorrhea (4%) accounted for most of the remainder of the complaints. Sixteen percent of these patients were asymptomatic, and the tumors were found incidentally during other operative procedures. Other associated symptoms were weight loss, malaise, fatigue, and mild glucose intolerance. These nonspecific symptoms may lead to confusion in differential diagnosis, especially with respect to pancreatic carcinoma and chronic pancreatitis. This was the case with several of our patients (Table 1). Patient 1 presented with abdominal pain and elevated serum amylase and later had obstructive jaundice. Patient 2 presented with steatorrhea and weight loss. Table 1. Summary of clinical symptoms and ERCP findings Patient no. 1a
2
3
4a 5
Symptoms
ERCP findings
Abdominal pain Chronic pancreatitis; ? stricture of retropapillary pancreatic duct Jaundice Effacement, displacement of common bile duct; stenosis of retropapillary pancreatic duct Steatorrhea Displacement of common bile duct; obstruction of pancreatic duct Abdominal pain Displacement, effacement of pancreatic duct Abdominal pain Constriction of pancreatic duct Abdominal pain Displacement of pancreatic duct Abdominal pain Effacement, displacement of pancreatic duct
a Patients 1 and 4 had two ERCP examinations apiece, each 14 months apart.
VOLUME 34, NO.1, 1988
Patients 3, 4, and 5 all had abdominal pain and abnormal CT findings that suggested a pancreatic disorder. ERCP can be of significant benefit in the differential diagnosis provided the diagnosis of islet cell tumor is considered. The ERCP findings in all five of our patients included either displacement or effacement of the pancreatic or common bile duct (Table 1). Although the possibility of a pancreatic islet cell tumor was not initially considered on the basis of the pancreatogram, in retrospect there were characteristic findings that suggested this diagnosis. The first ERCP study obtained for patient 1 was thought to be consistent with chronic pancreatitis. In retrospect, the retropapillary portion of the pancreatic duct was not opacified very well, and this could have been interpreted as suggesting a stricture. Weare not aware of any reports of a pancreatic islet cell tumor that produced ERCP findings of chronic pancreatitis. The second ERCP study 1 year later in this patient showed stenosis of the retropapillary portion of the pancreatic duct as well as displacement and effacement of the common bile duct. ERCP for patient 2 also showed displacement of the common bile duct. Displacement and/or effacement of the main pancreatic duct was evident on the pancreatogram for patients 3, 4, and 5. Although signs and symptoms as well as laboratory values and the results of other imaging methods in each of our patients suggested one of the more common diseases of the pancreas, the pancreatographic findings in each case were not entirely consistent with chronic pancreatitis or pancreatic adenocarcinoma. Rather than the characteristic ductal obstruction seen with adenocarcinoma there was evidence in each case of distortion and displacement of the main pancreatic duct, findings that are highly unusual or at least difficult to appreciate with adenocarcinoma. Careful study of each of the pancreatograms suggested a process that displaced normal pancreatic ductal and acinar tissues, in contrast to the destructive changes of both large and small ducts associated with pancreatic adenocarcinoma and chronic pancreatitis. We conclude that islet cell tumors can produce an unusual and unique retrograde pancreatochloangiographic appearance. In the differential diagnosis of pancreatic disorders, especially the differential diagnosis of adenocarcinoma in a patient with a pancreatic mass, these radiographic findings should raise the suspicion of an islet cell tumor when any aspect of the clinical evaluation, such as symptoms of long duration, is not entirely consistent with the more common diagnoses of carcinoma or chronic pancreatitis. ACKNOWLEDGMENT
The authors thank Jane Salamon for expert secretarial assistance. 51
REFERENCES 13. 1. Cotton PB. Progress report ERCP. Gut 1977;18:316-41. 2. Katon RM, Lee TG, Parent JA, Bilbao MK, Smith FW. Endoscopic retrograde cholangiopancreatography (ERCP). Experience with 100 cases. Am J Dig Dis 1974;19:295-306. 3. Vennes JA, Silvis SE. Endoscopic visualization of bile and pancreatic ducts. Gastrointest Endosc 1972;18:149-52. 4. Plumley TF, Rohrmann CA, Freeny PC, Silverstein FE, Ball TJ. Double duct sign: reassessed significance in ERCP. Am J RoentgenoI1982;138:31-5. 5. Rohrmann CA, Silvis SE, Vennes JA. The significance of pancreatic ductal obstruction in differential diagnosis of the abnormal endoscopic retrograde pancreatogram. Radiology 1976;121:311-4. 6. Foley WD, Stewart ET, Lawson TL, et a1. Computed tomography, ultrasonography, and endoscopic retrograde cholangiopancreatography in the diagnosis of pancreatic disease: a comparative study. Gastrointest Radiol 1980;5:29-35. 7. Silvis SE, Rohrmann CA, Vennes JA. Diagnostic accuracy of endoscopic retrograde cholangiopancreatography in hepatic, biliary, and pancreatic malignancy. Ann Intern Med 1976;84:438-40. 8. Moss AA, Federle M, Shapiro HA, et al. The combined use of computed tomography and endoscopic retrograde cholangiopancreatography in the assessment of suspected pancreatic neoplasm: a blind clinical evaluation. Radiology 1980;134:15963. 9. Ralls PW, Halls J, Renner I, Juttner H. Endoscopic retrograde cholangiopancreatography (ERCP) in pancreatic disease. A reassessment of the specificity of ductal abnormalities in differentiating benign from malignant disease. Radiology 1980;134:347-52. 10. DiMagno EP, Malagelada JR, Taylor WF, Go VLW. A prospective comparison of current diagnostic tests for pancreatic cancer. N Engl J Med 1977;297:737-42. 11. Reuben A, Cotton PB. Endoscopic retrograde cholangiopancreatography in carcinoma of the pancreas. Surg Gynecol Obstet 1979;148:179-84. 12. Anacker H, Weiss HD, Kramann B. Endoscopic retrograde
Microcystic adenoma of the pancreas demonstrated by endoscopic retrograde pancreatography
14.
15.
16. 17.
18.
19. 20. 21. 22. 23. 24.
pancreaticocholangiography in chronic diseases of the pancreas and in papillary stenoses. Gastrointest Radiol 1978;3:325-34. Suzuki T, Imamura M, Tamura K, et a1. Correlative evaluation of angiography and pancreatoductography in relation to surgery for cancer of the pancreas. Surgery 1979;85:644-51. Nix GAJJ, Schmitz PIM, Wilson JHP, Van Blankenstein M, Groeneveld CFM, Hofwijk R. Carcinoma of the head of the pancreas. Therapeutic implications of endoscopic retrograde cholangiopancreatography findings. Gastroenterology 1984; 87:37-43. Podolsky DK, McPhee MS, Alpert E, Warshaw AL, Isselbacher KJ. Galactosyltransferase isoenzyme II in the detection of pancreatic cancer: comparison with radiographic, endoscopic, and serologic tests. N Engl J Med 1981;304:1313-8. Rohrmann CA, Silvis SE, Vennes JA. Evaluation of the endoscopic pancreatogram. Radiology 1974;113:297-304. Freeny PC, Bilbao MK, Katon RM. "Blind" evaluation of endoscopic retrograde cholangiopancreatography (ERCP) in the diagnosis of pancreatic carcinoma: the "double duct" and other signs. Radiology 1976;119:271-4. Kruse A, Thommesen P, Fredericksen P. Endoscopic retrograde cholangiopancreatography in pancreatic cancer and chronic pancreatitis. Differences in morphologic changes in the pancreatic duct and the bile duct. Scand J Gastroenterol 1978;13:513-7. Freeny PC, Ball TJ. Evaluation of endoscopic retrograde cholangiopancreatography and angiography in the diagnosis of pancreatic carcinoma. Am J RoentgenoI1978;130:683-91. Fabozzi S. Ueber die histogenese des primaren krebses des pankreas. Beitr PathoI1903;34:199-214. Moldow RE, Connelly RR. Epidemiology of pancreatic cancer in Connecticut. Gastroenterology 1968;55:677-86. Kent RB III, Van Heerden JA, Weiland LH. Nonfunctioning islet cell tumors. Ann Surg 1981;193:185-90. Prinz RA, Badrinath K, Chejfec G, Freeark RJ, Greenlee HB. "Nonfunctioning" islet cell carcinoma of the pancreas. Am Surg 1983;49:345-9. Moertel CG, Hanley JA, Johnson LA. Streptozotocin alone compared with streptozotocin plus fluorouracil in the treatment of advanced islet cell carcinoma. N Engl J Med 1980;303:118994.
ular, and that usually form papillae lined with columnar, mucin-producing epithelium. Most of these neoplasms contain either adenocarcinoma (cystadenocarcinoma) or markedly atypical columnar epithelium.
R. Delcenserie, MD J.-L. Dupas, MD J.-P. Joly, MD P. Descombes, MD F. Mortier, MD J.-P. Capron, MD
Cystadenoma of the pancreas may be divided into two distinct groupS.l.2 The first is microcystic adenoma, which is composed of tiny cysts ranging from less than 1 to 2 cm in diameter, lined by flattened or cuboidal cells whose cytoplasm contains glycogen and little or no mucin; these are benign. The second is mucinous cystadenoma, which is composed of large cystic spaces that can be either unilocular or multilocFrom the Service d'Hepato-gastroenterologie, C.H. U. Nord, 80030 Amiens Cedex, France. Reprint requests: Dr. R. Delcenserie at the above address.
52
Figure 1. Abdominal ultrasonography: cystic mass with echogenic areas (arrow) in the tail of the pancreas. GASTROINTESTINAL ENDOSCOPY
2. Huibregtse K, Tytgat GN. Palliative treatment of obstructive jaundice by transpapillary introduction of large bore bile duct endoprosthesis: experience in 45 patients. GUT 1982;23:371-5. 3. Huibregtse K, Tytgat GNJ. Endoscopic placement of biliary prosthesis. In: Salmon PR, ed. Gastrointestinal endoscopyadvances in diagnosis and therapy, vol 1. Baltimore: Williams & Wilkins, 1984:219-31. 4. Brambs JH, Billmann P, Pausch J, Holslege A, Salm R. Nonsurgical biliary drainage: endoscopic conversion of percutaneous transhepatic into endoprosthetic drainage. Endoscopy 1986;18:52-4. 5. Hagenmuller F. Results of endoscopic bilioduodenal drainage in malignant bile duct stenosis. In: Classen M, Geenen J, Kawai K, eds. Nonsurgical biliary drainage. Berlin: Springer-Verlag, 1984:93-104. 6. Classen M, Hagenmuller F. Endoscopic biliary drainage. Scand J GastroenteroI1984;19(suppl 2):76-83. 7. Tytgat GNJ, Bartelsman JFWM, Den Hartog Jager FCA, Huibregtse K, Mathus-Vliegen EMH. Upper intestinal and biliary tract endoprosthesis. Dig Dis Sci 1986;31(9-Sep suppl):67S76S. 8. Tsang TK, Crampton AR, Bernstein JR, Ramos SR, Wieland JM. Percutaneous-endoscopic biliary stent placement: preliminary report. Ann Intern Med 1987;106:389-92. 9. Kerlan RK, Ring EJ, Pogany AC, Jeffrey RB. Biliary endoprosthesis insertion using a combined peroral-transhepatic method. Radiology 1984;150:828-30.
Case Reports Endoscopic retrograde cholangiopancreatography in pancreatic islet cell tumors Allen R. Kaufman, MD Michael V. Sivak, Jr., MD D. Roy Ferguson, MD
Endoscopic retrograde cholangiopancreatography (ERCP) is a well established technique in the evaluation of patients with suspected pancreatic disease. 1- 3 Specific signs of pancreatic disorders have been recognized as experience with this modality has increased. 4- 7 We report five cases of pancreatic islet cell tumors with pancreatographic findings that differ from those of pancreatic adenocarcinoma. CASE REPORTS Case 1
A 28-year-old white woman was referred to our institution and had a 2-month history of abdominal pain, 15-pound weight loss, and elevated serum amylase. There was no From the Department of Gastroenterology, Cleveland Clinic Foundation, Cleveland, Ohio. Reprint requests: Michael V. Sivak, Jr., MD, Department of Gastroenterology, Cleveland Clinic Foundation, 9500 Euclid Avenue, Cleveland, Ohio 44106. VOLUME 34, NO.1, 1988
history of alcohol abuse. Ultrasonography of the gallbladder was normal. ERCP revealed a dilated and irregular pancreatic duct that was thought to be consistent with chronic pancreatitis (Fig. 1). More than a year later the patient returned, having been hospitalized twice during the previous year for epigastric pain and diarrhea. At that time, she noted a 2-week history of worsening midepigastric pain, diarrhea, jaundice, and pruritis. Her weight had been stable for the past year. On laboratory evaluation the total bilirubin level was 10.0 mg/ 100 ml (normal, 0 to 1.4 mg/l00 ml), alkaline phosphatase level was 350 units/liter (normal, 20 to 110 units per liter), SGOT level was 103 units/liter (normal, 7 to 40 units/liter), and the serum amylase level was 158 units/liter (normal, 10 to 135 units/liter). Ultrasonography disclosed dilation of the intrahepatic and extrahepatic biliary ducts and enlargement of the head of the pancreas. ERCP also demonstrated common bile and intrahepatic duct dilation. There was also marked narrowing, effacement, and lateral displacement of the distal common bile duct (Fig. 2A). Moderate generalized dilation of the pancreatic duct was also present, and there was an area of stenosis in the retropapillary portion of the main pancreatic duct (Fig. 2B). An exploratory laparotomy was performed, and the patient underwent a Whipple procedure for a 3-cm metastatic islet cell tumor of the head ofthe pancreas. All of the four peripancreatic lymph nodes showed evidence of tumor. 47
Figure 1. Retrograde pancreatogram (patient 1) demonstrates a dilated, irregular pancreatic duct. The common bile duct is normal.
Case 2
This 45-year-old white man had a 6-month history of diarrhea with foul-smelling stools and an associated 40pound weight loss. A 72-hour stool fecal fat collection revealed 67 g of fat. A small bowel biopsy was normal. Computed tomography (CT) revealed a lobulated head of the pancreas but was otherwise normal. ERCP disclosed two persistent filling defects over the lateral aspect of the distal common bile duct (Fig. 3). There was an increased medial convexity of the distal common duct that was consistent with displacement. The pancreatic duct filled poorly with contrast material and was not visualized beyond the head. The visualized portion suggested dilation of the main pancreatic duct branches. A duodenal ulcer in the apex of the bulb was noted at ERCP. The patient underwent exploratory laparotomy at which a 3-cm tumor confined to the head of the pancreas was found. A Whipple procedure was performed. The pathologic specimen included an islet cell tumor of the pancreas that had extended into the duodenal wall with associated duodenal mucosal ulceration. Seven peripancreatic lymph nodes were all negative for malignancy. Case 3
A 53-year-old white man was referred and had a 3-month history of constipation, upper abdominal pain radiating to the back, and an associated 35-pound weight loss. Laboratory tests showed normal serum total bilirubin, amylase, and lipase, although the alkaline phosphatase level was 264 units/liter. CT demonstrated a mass involving the head of the pancreas. ERCP disclosed narrowing of the distal portion of the pancreatic duct with displacement and effacement of a branch to the uncinate process (Fig. 4). These findings were thought to suggest a mass lesion, but they were not considered definite. CT-guided needle aspiration biopsy of the pancreatic mass revealed abnormal cells consistent with a nonductal epithelial neoplasm of islet cell or carcinoid origin. 48
Figure 2. A, Second retrograde cholangiOgram in same patient as Figure 1 (patient 1) obtained 14 months later, demonstrating dilation of the common bile duct as well as narrowing, effacement, and lateral displacement of the distal common bile duct (arrow). B, Moderate generalized dilation of the pancreatic duct is shown along with stenosis of the duct in the retropapillary portion (arrows).
The patient underwent an exploratory laparotomy, and a large irregularly formed mass was found that arose from the pancreas and extended anteriorly. A cholecystojejunostomy was performed. Pathologic examination of the resected mass disclosed an islet cell carcinoma with involvement of gastrocolic and celiac nodes. The patient was treated with 5fluorouracil and chlorazotocin. Case 4
A 70-year-old white man was referred to our institution and had a 3-month history of lower abdominal pain, alternating diarrhea and constipation, and elevated serum amylase and lipase values. Previous ultrasonography of the gallbladder had been negative. There was no history of alcohol abuse. Four years earlier, the patient had undergone GASTROINTESTINAL ENDOSCOPY
Figure 3. Retrograde cholangiogram (patient 2) demonstrating displacement of distal lower common bile duet with persistent filling defects over the lateral aspect (arrows). The main pancreatic duct branches are dilated, although the pancreatic duct is not visualized beyond the portion in the head (curved arrow).
excision and drainage of the pancreatic pseudocyst. There was no evidence of tumor at laparotomy. Five months later the patient was rehospitalized and had recurrent abdominal pain, nausea, and elevated serum amylase level (2,500 units). CT of the abdomen showed a mass in the body and tail of the pancreas. The serum total bilirubin level was 1.0 mg/lOO ml and alkaline phosphatase was 1160 unitsfliter. ERCP disclosed relative narrowing of the pancreatic duct in the head with no filling of main pancreatic duct side branches (Fig. 5). The main duct in the body of the pancreas was markedly dilated, and there was no opacification of main-duct branches. Pancreatography in the region of the tail showed a constricted segment along with some dilated, sacculated, ectatic branch ducts. The patient underwent laparotomy with distal pancreatectomy for an islet cell tumor of the pancreatic tail, along with an end to end pancreaticojejunostomy and an end to side cholecystojejunostomy. The pancreatic islet cell tumor was histologically identical to the lung tumor that had been resected in 1974. Fourteen months later the patient was readmitted and had recurrent abdominal pain, nausea, and an associated 10-pound weight loss. The serum total bilirubin level was 0.6 mg/loo ml and alkaline phosphatase was 175 units/liter. CT of the abdomen showed no pancreatic mass. A repeat ERCP study showed distortion of the pancreatic duct in the head with marked medial displacement and narrowing (Fig. 6). A few of the main pancreatic duct branches in the head were dilated and ectatic. There was acute angulation of the main pancreatic duct in the region of the junction of the head and body. The duct in the body of the gland was dilated and showed no opacification of its branches. Contrast medium drained via the pancreaticojejunostomy. The overall appearance of the pancreatogram
Figure 4. Retrograde pancreatogram (patient 3) suggesting distal pancreatic duct narrowing with displacement and effacement of a branch to the uncinate process (arrow).
resection of the lower lobe of the left lung for a spindle-cell carcinoid tumor. Laboratory evaluation showed serum total bilirubin level of 3.4 mg/loo ml, alkaline phosphatase 350 units/liter, SGOT 85 units/liter, and amylase 988 units. CT revealed a large pseudocyst in the head of the pancreas. One week later the patient underwent exploratory laparotomy with partial VOLUME 34, NO.1, 1988
Figure 5. Retrograde pancreatogram (patient 4) demonstrating relative narrowing of the pancreatic duct in the head (short arrow), dilation of the duct in the body (long arrow), and a constricted area in the tail (curved arrow) with dilated sacculated and ectatic branches. There is no filling of main duct branches in the head or body. 49
Figure 6. Repeat retrograde pancreatogram (patient 4) 14
Figure 7. Retrograde pancreatogram (patient 5) showing
months after the pancreatogram in Figure 5, demonstrating medial displacement and narrowing of the main pancreatic duct in the head (short arrow) with dilated ectatic branches. The duct in the body is dilated with no opacification of side branches. Note the acute angulation at the junction of the head and body (long arrow). Contrast medium injected at the duodenal papilla drains via the pancreaticojejunostomy (curved arrow).
effacement and displacement of the main pancreatic duct in the head (small arrows). The duct in the body is dilated relative to the diameter of that in the head, and the side branches are dilated. The main duct in the head fills poorly, while the accessory duct (long arrow) fills readily. Effacement of opacified acinar tissue (wide arrow) is noted near the medial wall of the descending duodenum.
suggested displacement of the main pancreatic duct by a mass. The patient was treated conservatively with bilateral celiac plexus blocks for control of pain. Chemotherapy was refused.
the main pancreatic duct or its branches. The reported sensitivity of ERCP in the recognition of pancreatic adenocarcinoma has been in excess of 90% in most series. 7- 15 There are several characteristic pancreatographic findings: an abrupt or gradual occlusion of the main duct; stenosis of the main duct with or without prestenotic ectasia; and changes in the main duct branches, such as fragmentation and cystic destruction; displacement of ductules; and pooling of contrast material in irregular pockets of a necrotic tumor mass. 12 In addition, stenosis of the common bile duct with an irregular shouldering may be noted. It is well recognized that chronic pancreatitis can produce similar ductal changes. 9 ,12 Stricture or obstruction of both the bile duct and pancreatic duct at the same level, the double duct sign, is a very reliable sign of pancreatic malignancy, although this finding is not pathogonomic of carcinoma since similar findings are noted in chronic pancreatitis. 4 , 9,16 Specific ductal characteristics suggestive of malignancy include ductal obstruction, especially of the common bile duct, close proximity of the biductallesions, a short stenotic segment of the common bile duct removed from the papilla, and an abrupt irregular transition from normal to stenotic or obstructed duct. 4 ,17-19 Pancreatic islet cell carcinoma was first reported by Fabozzi in 1903. 20 Islet cell tumors are rare, with a prevalence estimated at less than 1/100,000 of the population. 21 In one large series of islet cell tumors 60% were insulinomas, 18% gastrinomas, and 15%
Case 5
A 59-year-old black woman was referred and had a 4month history of epigastric pain. She had no history of alcohol abuse or of gallstones. Previous ultrasonography and CT of the abdomen had been interpreted as showing a pseudocyst of the head of the pancreas. ERCP showed effacement of the main pancreatic duct in the head of the pancreas (Fig. 7). The main duct in the region of the head filled poorly with contrast material. The accessory duct, however, was readily opacified. There was opacification of the pancreatic ductal system to the acinar level in the head of the pancreas, and acinar filling was noted as a faint blush along the duodenal wall. The main pancreatic duct was dilated in the body relative to the diameter of the duct in the head, and the main duct branches in this portion were also dilated. The overall appearance of the pancreatogram suggested a mass in the head of the pancreas that was displacing normal ductal and acinar tissues. The patient underwent exploratory laparotomy and excision of a lO-cm islet cell tumor of the head of the pancreas. DISCUSSION
Most pancreatic malignancies are adenocarcinomas that arise in the ductal system, so that even small lesions will usually produce stenosis or occlusion of 50
GASTROINTESTINAL ENDOSCOPY
nonfunctioning. 22 Islet cell tumors, in contrast to ductal carcinomas of the pancreas, are generally slow growing, and the presence of metastases does not exclude prolonged survival,22.23 Kent et al. 22 reported 3- and 5-year survival rates of 60% and 44%, respectively, for pancreatic islet cell tumors. Nonfunctioning islet cell tumors are more amenable to treatment than pancreatic adenocarcinoma. An aggressive surgical approach has generally been recommended. Kent et al. 22 have reported survival as long as 12 and 26 years after Whipple procedure for this tumor. Survival after biliary bypass procedures in patients with liver metastases may also be prolonged relative to that for patients with metastatic pancreatic adenocarcinoma. Chemotherapy is much more likely to be of benefit in patients with islet cell carcinoma; response rates of over 60% have been reported with combined streptozocin and 5-fluorouracil therapy.24 The clinical presentation of nonfuctioning islet cell tumors is nonspecific. In one series of 25 such patients, the most frequent presenting complaints were pain (36%) and jaundice (28%) due to the mass effect of the tumor and invasion of surrounding structures. 22 Ascites (4%), a palpable mass (8%), confusion (4%), and steatorrhea (4%) accounted for most of the remainder of the complaints. Sixteen percent of these patients were asymptomatic, and the tumors were found incidentally during other operative procedures. Other associated symptoms were weight loss, malaise, fatigue, and mild glucose intolerance. These nonspecific symptoms may lead to confusion in differential diagnosis, especially with respect to pancreatic carcinoma and chronic pancreatitis. This was the case with several of our patients (Table 1). Patient 1 presented with abdominal pain and elevated serum amylase and later had obstructive jaundice. Patient 2 presented with steatorrhea and weight loss. Table 1. Summary of clinical symptoms and ERCP findings Patient no. 1a
2
3
4a 5
Symptoms
ERCP findings
Abdominal pain Chronic pancreatitis; ? stricture of retropapillary pancreatic duct Jaundice Effacement, displacement of common bile duct; stenosis of retropapillary pancreatic duct Steatorrhea Displacement of common bile duct; obstruction of pancreatic duct Abdominal pain Displacement, effacement of pancreatic duct Abdominal pain Constriction of pancreatic duct Abdominal pain Displacement of pancreatic duct Abdominal pain Effacement, displacement of pancreatic duct
a Patients 1 and 4 had two ERCP examinations apiece, each 14 months apart.
VOLUME 34, NO.1, 1988
Patients 3, 4, and 5 all had abdominal pain and abnormal CT findings that suggested a pancreatic disorder. ERCP can be of significant benefit in the differential diagnosis provided the diagnosis of islet cell tumor is considered. The ERCP findings in all five of our patients included either displacement or effacement of the pancreatic or common bile duct (Table 1). Although the possibility of a pancreatic islet cell tumor was not initially considered on the basis of the pancreatogram, in retrospect there were characteristic findings that suggested this diagnosis. The first ERCP study obtained for patient 1 was thought to be consistent with chronic pancreatitis. In retrospect, the retropapillary portion of the pancreatic duct was not opacified very well, and this could have been interpreted as suggesting a stricture. Weare not aware of any reports of a pancreatic islet cell tumor that produced ERCP findings of chronic pancreatitis. The second ERCP study 1 year later in this patient showed stenosis of the retropapillary portion of the pancreatic duct as well as displacement and effacement of the common bile duct. ERCP for patient 2 also showed displacement of the common bile duct. Displacement and/or effacement of the main pancreatic duct was evident on the pancreatogram for patients 3, 4, and 5. Although signs and symptoms as well as laboratory values and the results of other imaging methods in each of our patients suggested one of the more common diseases of the pancreas, the pancreatographic findings in each case were not entirely consistent with chronic pancreatitis or pancreatic adenocarcinoma. Rather than the characteristic ductal obstruction seen with adenocarcinoma there was evidence in each case of distortion and displacement of the main pancreatic duct, findings that are highly unusual or at least difficult to appreciate with adenocarcinoma. Careful study of each of the pancreatograms suggested a process that displaced normal pancreatic ductal and acinar tissues, in contrast to the destructive changes of both large and small ducts associated with pancreatic adenocarcinoma and chronic pancreatitis. We conclude that islet cell tumors can produce an unusual and unique retrograde pancreatochloangiographic appearance. In the differential diagnosis of pancreatic disorders, especially the differential diagnosis of adenocarcinoma in a patient with a pancreatic mass, these radiographic findings should raise the suspicion of an islet cell tumor when any aspect of the clinical evaluation, such as symptoms of long duration, is not entirely consistent with the more common diagnoses of carcinoma or chronic pancreatitis. ACKNOWLEDGMENT
The authors thank Jane Salamon for expert secretarial assistance. 51
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ular, and that usually form papillae lined with columnar, mucin-producing epithelium. Most of these neoplasms contain either adenocarcinoma (cystadenocarcinoma) or markedly atypical columnar epithelium.
R. Delcenserie, MD J.-L. Dupas, MD J.-P. Joly, MD P. Descombes, MD F. Mortier, MD J.-P. Capron, MD
Cystadenoma of the pancreas may be divided into two distinct groupS.l.2 The first is microcystic adenoma, which is composed of tiny cysts ranging from less than 1 to 2 cm in diameter, lined by flattened or cuboidal cells whose cytoplasm contains glycogen and little or no mucin; these are benign. The second is mucinous cystadenoma, which is composed of large cystic spaces that can be either unilocular or multilocFrom the Service d'Hepato-gastroenterologie, C.H. U. Nord, 80030 Amiens Cedex, France. Reprint requests: Dr. R. Delcenserie at the above address.
52
Figure 1. Abdominal ultrasonography: cystic mass with echogenic areas (arrow) in the tail of the pancreas. GASTROINTESTINAL ENDOSCOPY