75-Year-Old Man With Abdominal Pain and Weight Loss

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Mayo Clin Proc. October 2008;83(10):1161-1164 www.mayoclinicproceedings.com 1161 For personal use. Mass reproduce only with permission from Mayo Clinic Proceedings. For personal use. Mass reproduce only with permission from Mayo Clinic Proceedings. 75-Year-Old Man With Abdominal Pain and Weight Loss RESIDENTS' CLINIC MICHAEL D. LEISE, MD*; KURT M. JACOBSON, MD*; AND SURESH T. CHARI, MD† *Resident in Internal Medicine, Mayo School of Graduate Medical Education, Mayo Clinic, Rochester, MN. †Adviser to residents and Consultant in Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN. See end of article for correct answers to questions. Individual reprints of this article are not available. Address correspondence to Suresh T. Chari, MD, Division of Gastroenterology and Hepatology, Mayo Clinic, 200 First St SW, Rochester, MN 55905 ([email protected]). © 2008 Mayo Foundation for Medical Education and Research A 75-year-old man presented to the outpatient clinic with a 9-kg weight loss during the preceding several months and mild midepigastric pain radiating to the back. His medical history was unremarkable. He was a former smoker and lifelong nondrinker. Review of systems was notable only for a slightly decreased appetite, but no nau- sea, vomiting, or diarrhea was reported. On physical ex- amination, the patient was afebrile and had normal vital signs. However, cachexia and jaundice with scleral icterus were evident. Abdominal examination revealed mild midepigastric tenderness without rebound, guarding, or hepatosplenomegaly and a negative Murphy sign. Findings on the rest of the physical examination were unremarkable. Results of a complete blood cell count and electrolyte studies were within normal limits. Additional test results included the following (reference ranges provided paren- thetically): alanine aminotransferase, 425 U/L (7-55 U/L); aspartate aminotransferase, 127 U/L (8-48 U/L); alkaline phosphatase, 582 U/L (45-115 U/L); total bilirubin, 8.9 mg/dL (0.1-1.10 mg/dL); direct bilirubin, 7.1 mg/dL (0.0- 0.3 mg/dL); and lipase, less than 10 U/L (10-73 U/L). The erythrocyte sedimentation rate was elevated at 71 mm/1 h (0-22 mm/1 h). Hepatitis testing that included hepatitis B surface antigen, IgM antibodies to hepatitis B core antigen, and hepatitis C virus (enzyme immunoassay) yielded normal results. 1. In this patient, which one of the following is the most likely diagnosis? a. Acute pancreatitis b. Cholecystitis c. Acute hepatitis d. Pancreatic carcinoma e. Cholangitis Acute pancreatitis is an acute inflammatory process usu- ally associated with severe abdominal pain and elevated serum levels of pancreatic enzymes. The lipase level below 10 U/L in this patient does not support this diagnosis. Bilirubin and alkaline phosphatase elevations as high as those in this patient are not common in uncomplicated cholecystitis because biliary obstruction is usually limited to the cystic duct and gallbladder. Although elevated liver transaminase levels could suggest hepatitis, the degree of alkaline phosphatase elevation (>5 times the upper limit of normal), weight loss, and patient age suggest an obstructive process. Therefore, acute hepatitis is not the most likely diagnosis. The constellation of epigastric pain radiating to the back, cachexia, and jaundice makes pancreatic carci- noma the most likely diagnosis. Cholangitis would be con- cerning in this patient with evidence of biliary obstruction and abdominal pain; however, the normal leukocyte count, lack of fever, and insidious course make this diagnosis less likely. After the initial evaluation of the patient, further imaging studies were required to confirm the presumptive diagnosis. 2. Which one of the following imaging studies would be most appropriate in this patient? a. Ultrasonography (US) of the abdomen b. Computed tomography (CT) of the abdomen c. Magnetic resonance imaging of the abdomen d. Endoscopic retrograde cholangiopancreatography (ERCP) e. Esophagogastroduodenoscopy Abdominal US would be appropriate if acute cholecysti- tis or cholangitis were suspected. The visualization of gall- stones in conjunction with either a positive sonographic Murphy sign or gallbladder wall thickening provides a positive predictive value greater than 90% for the diagnosis of cholecystitis. Abdominal US is also more sensitive than CT for detecting biliary dilatation from common bile duct stones. However, this patient’s clinical findings suggest a malignant process involving the biliary tree or pancreas. Therefore, CT is the most appropriate initial imaging mo- dality because it is more sensitive and specific than US for pancreatic cancer. 1 Although CT and magnetic reso- nance imaging have similar sensitivity and specificity for the diagnosis of extrahepatic malignancies, CT is easier and less expensive to perform. 2 Endoscopic retrograde cho- langiopancreatography is preferably used when therapy is likely to be needed after a pancreatobiliary process ame- nable to ERCP has been identified on less invasive imag- ing. Because of the substantially greater potential for seri- ous complications associated with ERCP, it is not ideal for initial evaluation. Esophagogastroduodenoscopy would be inappropriate for this patient who has evidence of biliary obstruction.

Transcript of 75-Year-Old Man With Abdominal Pain and Weight Loss

Page 1: 75-Year-Old Man With Abdominal Pain and Weight Loss

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RESIDENTS’ CLINIC

For personal use. Mass reproduce only with permission from Mayo Clinic Proceedings.For personal use. Mass reproduce only with permission from Mayo Clinic Proceedings.

75-Year-Old Man With Abdominal Pain and Weight Loss

RESIDENTS' CLINIC

MICHAEL D. LEISE, MD*; KURT M. JACOBSON, MD*; AND SURESH T. CHARI, MD†

*Resident in Internal Medicine, Mayo School of Graduate Medical Education,Mayo Clinic, Rochester, MN.

†Adviser to residents and Consultant in Gastroenterology and Hepatology,Mayo Clinic, Rochester, MN.

See end of article for correct answers to questions.

Individual reprints of this article are not available. Address correspondenceto Suresh T. Chari, MD, Division of Gastroenterology and Hepatology, MayoClinic, 200 First St SW, Rochester, MN 55905 ([email protected]).

© 2008 Mayo Foundation for Medical Education and Research

A 75-year-old man presented to the outpatient clinicwith a 9-kg weight loss during the preceding several

months and mild midepigastric pain radiating to the back.His medical history was unremarkable. He was a formersmoker and lifelong nondrinker. Review of systems wasnotable only for a slightly decreased appetite, but no nau-sea, vomiting, or diarrhea was reported. On physical ex-amination, the patient was afebrile and had normal vitalsigns. However, cachexia and jaundice with scleral icteruswere evident. Abdominal examination revealed mildmidepigastric tenderness without rebound, guarding, orhepatosplenomegaly and a negative Murphy sign. Findingson the rest of the physical examination were unremarkable.

Results of a complete blood cell count and electrolytestudies were within normal limits. Additional test resultsincluded the following (reference ranges provided paren-thetically): alanine aminotransferase, 425 U/L (7-55 U/L);aspartate aminotransferase, 127 U/L (8-48 U/L); alkalinephosphatase, 582 U/L (45-115 U/L); total bilirubin, 8.9mg/dL (0.1-1.10 mg/dL); direct bilirubin, 7.1 mg/dL (0.0-0.3 mg/dL); and lipase, less than 10 U/L (10-73 U/L). Theerythrocyte sedimentation rate was elevated at 71 mm/1 h(0-22 mm/1 h). Hepatitis testing that included hepatitis Bsurface antigen, IgM antibodies to hepatitis B core antigen,and hepatitis C virus (enzyme immunoassay) yielded normalresults.

1. In this patient, which one of the following is the mostlikely diagnosis?

a. Acute pancreatitisb. Cholecystitisc. Acute hepatitisd. Pancreatic carcinomae. Cholangitis

Acute pancreatitis is an acute inflammatory process usu-ally associated with severe abdominal pain and elevatedserum levels of pancreatic enzymes. The lipase level below10 U/L in this patient does not support this diagnosis.Bilirubin and alkaline phosphatase elevations as high asthose in this patient are not common in uncomplicatedcholecystitis because biliary obstruction is usually limitedto the cystic duct and gallbladder. Although elevated livertransaminase levels could suggest hepatitis, the degree ofalkaline phosphatase elevation (>5 times the upper limit ofnormal), weight loss, and patient age suggest an obstructiveprocess. Therefore, acute hepatitis is not the most likelydiagnosis. The constellation of epigastric pain radiating tothe back, cachexia, and jaundice makes pancreatic carci-

noma the most likely diagnosis. Cholangitis would be con-cerning in this patient with evidence of biliary obstructionand abdominal pain; however, the normal leukocyte count,lack of fever, and insidious course make this diagnosisless likely.

After the initial evaluation of the patient, further imagingstudies were required to confirm the presumptive diagnosis.

2. Which one of the following imaging studies would bemost appropriate in this patient?

a. Ultrasonography (US) of the abdomenb. Computed tomography (CT) of the abdomenc. Magnetic resonance imaging of the abdomend. Endoscopic retrograde cholangiopancreatography

(ERCP)e. Esophagogastroduodenoscopy

Abdominal US would be appropriate if acute cholecysti-tis or cholangitis were suspected. The visualization of gall-stones in conjunction with either a positive sonographicMurphy sign or gallbladder wall thickening provides apositive predictive value greater than 90% for the diagnosisof cholecystitis. Abdominal US is also more sensitive thanCT for detecting biliary dilatation from common bile ductstones. However, this patient’s clinical findings suggest amalignant process involving the biliary tree or pancreas.Therefore, CT is the most appropriate initial imaging mo-dality because it is more sensitive and specific than USfor pancreatic cancer.1 Although CT and magnetic reso-nance imaging have similar sensitivity and specificity forthe diagnosis of extrahepatic malignancies, CT is easierand less expensive to perform.2 Endoscopic retrograde cho-langiopancreatography is preferably used when therapy islikely to be needed after a pancreatobiliary process ame-nable to ERCP has been identified on less invasive imag-ing. Because of the substantially greater potential for seri-ous complications associated with ERCP, it is not ideal forinitial evaluation. Esophagogastroduodenoscopy would beinappropriate for this patient who has evidence of biliaryobstruction.

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Computed tomography of the abdomen and pelvis(Figure) revealed marked intrahepatic and extrahepatic bileduct dilatation with enhancement of the walls of the bileducts and diffuse sausage-shaped enlargement of the pan-creas. No discrete pancreatic or biliary mass was visualized.A marked soft-tissue prominence surrounded the abdominalaorta, suggestive of retroperitoneal fibrosis. Computed to-mography showed no obvious malignant process as thecause of our patient’s symptoms. Therefore, further imagingwith ERCP or magnetic resonance cholangiopancrea-tography (MRCP) was indicated to investigate the possibil-ity of a retained stone in the common bile duct.

Because the patient refused more invasive ERCP,MRCP was performed. The modality revealed multipledilated intrahepatic and extrahepatic bile ducts, thickenedand enhanced walls of the extrahepatic bile ducts, and amildly dilated and segmentally thickened main pancreaticduct extending to the level of the pancreatic head. Thepancreas was diffusely enlarged. No definitive pancreaticmass, bile duct stone, or other obstructing ductal lesion wasidentified.

3. Considering the MRCP findings in this patient, whichone of the following is the most likely diagnosis?

a. Pancreatic cancerb. Cholangiocarcinomac. Primary biliary cirrhosis (PBC)d. Primary sclerosing cholangitis (PSC)e. Autoimmune pancreatitis (AIP)

The patient had no evidence of pancreatic cancer orcholangiocarcinoma, but these diagnoses are still possiblegiven that many early carcinomas are difficult to visualizeon imaging. However, the absence of frank hepatobiliary orpancreatic cancer should lead to consideration of othercauses of obstructive jaundice. Although PBC can manifestas jaundice, this entity, which classically involves the smallbile ducts rather than the larger intrahepatic and extrahe-

patic duct involvement seen in this patient, usually occursin women. Thus, PBC was not probable in this patient. Thecharacteristic radiologic manifestations of PSC on MRCPor ERCP are multifocal stricturing and dilatation of intra-hepatic and/or extrahepatic ducts, referred to as the string ofbeads sign, which was absent in this case. The combinationof a diffusely enlarged pancreas, intrahepatic and extrahe-patic duct dilatation, diffuse irregular thickening of themain pancreatic duct and intrapancreatic duct, and retro-peritoneal fibrosis make AIP the most likely diagnosis.3

Further studies were needed to help confirm the diagno-sis of AIP.

4. In light of the constellation of radiologic findings inthis patient, which one of the following would be themost appropriate next step?

a. Referral for pancreaticoduodenectomyb. Antinuclear antibody testingc. Serum IgG4 determinationsd. Computed tomography–guided pancreatic biopsye. Endoscopic ultrasonography (EUS) with fine-needle

aspiration (FNA) biopsy

Diagnostic modalities are still warranted at this time,and referral for pancreaticoduodenectomy would be inap-propriate. Autoimmune pancreatitis is associated withother serologic abnormalities, including elevated titers ofγ-globulins, IgG, and a variety of antibodies includingantinuclear antibody, rheumatoid factor, anti–carbonic an-hydrase antibody, and antilactoferrin antibody. However,elevations of many of these antibodies, including anti-nuclear antibody, are nonspecific, especially in elderly pa-tients, and would not be the most helpful tests. Elevatedlevels of the IgG4 subset of IgG have been found to be asensitive and specific marker for AIP; therefore, IgG4 de-termination would be the next test of choice. Both CT-guided pancreatic biopsy and EUS with FNA biopsy havean important role in the diagnosis of AIP and would charac-

FIGURE. Computed tomographic images showing dilated intrahepatic and extrahepatic bile ducts (arrow) (left), diffusely enlarged pancreasand thickened and enhanced bile duct walls (arrow) (middle), and soft-tissue prominence surrounding abdominal aorta (arrow) (right).

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teristically reveal a lymphoplasmacytic infiltrate but wouldnot be the most appropriate next step because of invasive-ness and the cost of the procedures.

Serum IgG levels were obtained and revealed the fol-lowing: total IgG, 2620 mg/dL (600-1500 mg/dL); IgG1,1710 mg/dL (490-1140 mg/dL); IgG2, 857 mg/dL (150-640 mg/dL); IgG3, 124 mg/dL (20-110 mg/dL); and IgG4,548 mg/dL (8-140 mg/dL). The markedly elevated IgG4level was strongly suggestive of AIP. Other notable labora-tory test results included a random blood glucose level of650 mg/dL (70-100 mg/dL). The clinical history of mildepigastric pain, jaundice, and weight loss in conjunctionwith the finding of an enlarged sausage-shaped pancreaswith a peripheral halo on CT and a positive IgG4 teststrongly supported the diagnosis of AIP with associatedcholangitis. Thereafter, treatment recommendations weregiven to the patient.

5. Which one of the following would be the most appro-priate treatment for this patient?

a. Oral corticosteroidsb. Intravenous corticosteroidsc. Azathioprined. Pancreaticoduodenectomye. Pancreatic duct stent

During the initial presentation of AIP, oral corticoster-oids can relieve symptoms such as dyspepsia and cho-lestasis, resolve pancreatic swelling and biliary strictures,and ameliorate new-onset diabetes. Although such im-provement has been noted to occur spontaneously in con-servatively treated patients, corticosteroids appear to bringabout these improvements in structure and function consis-tently and rapidly and therefore represent the best treatmentoption. No data are available on the use of intravenouscorticosteroids for this condition. Azathioprine may have arole as a corticosteroid-sparing agent in patients who expe-rience relapse after withdrawal of corticosteroids butwould not be the initial drug of choice. Neither pancreat-icoduodenectomy nor pancreatic duct stent would provideclear benefit. These procedures are invasive and can beassociated with substantial morbidity.

Our patient’s initial symptoms resolved spontaneously.At 3, 6, and 12 months of follow-up, he had regained isletcell function and was managing his diabetes with diet andexercise.

DISCUSSION

This case emphasizes the need for careful clinical andradiologic evaluation of patients presenting with symptomsthat are suggestive of pancreatic carcinoma to avoid unnec-essary surgical intervention. Autoimmune pancreatitis is an

uncommon cause of benign fibroinflammatory pancreaticdisease that can mimic pancreatic adenocarcinoma clinicallyand radiologically.3 Autoimmune pancreatitis has beencalled lymphoplasmacytic sclerosing pancreatitis, primaryinflammatory pancreatitis, and sclerosing pancreatico-cholangitis. Retrospective studies have shown that, in morethan 2.5% of pancreaticoduodenectomies performed forsuspected adenocarcinoma of the pancreas, the patient ac-tually had AIP.4,5 Identifying AIP is important becausecorticosteroid therapy usually resolves most or all symp-toms that may prompt unnecessary Whipple procedures.6

Autoimmune pancreatitis is diagnosed most commonlyin male patients, with a 2:1 male-female ratio. Age atpresentation is variable, with ranges reported from 30 to 80years, but the disorder occurs most commonly in the sixthdecade of life. Patients with AIP often present with symp-toms suggestive of mild pancreatitis, including mild ab-dominal pain, weight loss, jaundice, and an obstructivepattern on liver tests, but the disease is associated withless pain than chronic pancreatitis. In the past, it has been“associated” with other autoimmune diseases, includingPSC and Sjögren syndrome.7 However, recent studies sug-gest that these “associations” are in fact extrapancreaticmanifestations of AIP that mimic other disease states.8

Radiologic studies are often performed during the work-up of patients with abdominal pain. Although some symp-toms that occur in AIP can mimic those of other diseaseprocesses being considered, certain findings are more char-acteristic of AIP. Radiologic features suggestive of AIPinclude focal or diffuse pancreatic enlargement with mini-mal peripancreatic inflammation and the absence of vascu-lar encasement on CT or EUS.3 Diffuse irregular narrowingof the main pancreatic duct with associated multiple stric-tures can be seen on ERCP.3 The 2002 Japan PancreasSociety criteria9 for the diagnosis of AIP relied heavily onradiologic characteristics and mandated that imaging stud-ies display diffuse enlargement of the pancreas along withdiffuse (>33%) main pancreatic duct narrowing with anirregular wall. Recently, these criteria were revised to in-clude patients with focal enlargement and/or focal pancre-atic duct strictures.10 A recent report of the experience withAIP at Mayo Clinic supported multiple radiologic presen-tations, including a minority of patients with classic diffusepancreatic enlargement, a majority with focal enlargement,and other presentations, including a distinct mass, typicalacute pancreatitis changes, and a normal gland.8 Retroperito-neal fibrosis and biliary strictures have also been reported.8

Characteristic histologic findings are dense periductaland stromal lymphoplasmacytic infiltrates with stromal fi-broplastic proliferation.11 Tissue biopsy is often attemptedto assist with the diagnosis of AIP. However, one seriesfound needle or wedge biopsies of the pancreas to be

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diagnostic only 50% of the time.12 Adding an IgG4 immu-nostain to histologic studies can greatly enhance sensitiv-ity, as demonstrated in a recent publication.8

Hamano et al6 investigated the sensitivity and specific-ity of serum IgG4 for the diagnosis of AIP. Patients withAIP were found to have markedly elevated levels of IgG4,a rare immunoglobulin that can bind the C1q complementand activate the classic complement pathway. These inves-tigators described significantly higher IgG4 serum levels inpatients with AIP in contrast to those in patients withadenocarcinoma of the pancreas, chronic pancreatitis, PSC,PBC, or Sjögren syndrome. The trigger for the IgG4 eleva-tion and its pathogenetic role in AIP are unknown.

Currently, the proposed diagnostic criteria for AIP in-clude those from the Japan Pancreas Society9,10 and theMayo Clinic HISORt criteria proposed by Chari et al.8 TheHISORt criteria suggest that to identify the full spectrum ofchanges associated with AIP, one must recognize its 5cardinal features involving findings on histology, imaging,and serology; other organ involvement; and response tocorticosteroid therapy. The diagnosis of AIP can be estab-lished in patients with 1 or more of the following: (1)diagnostic histologic results, (2) characteristic features onpancreatic imaging and abnormal serologic findings, or(3) pancreatic disease with abnormal serologic results and/or other organ involvement that responds to corticosteroidtherapy. The HISORt criteria consider a wide range ofdisease manifestations, deemphasize radiologic findings asthe sine qua non for diagnosis, and emphasize both histo-logic findings and IgG4 immunostaining of pancreatic corebiopsy specimens as a possible criterion standard for diag-nosis. In cases in which AIP is strongly suspected buthistologic findings are unavailable and the results of imag-ing studies are not classic, response to corticosteroid therapycan be used as a diagnostic test.

Autoimmune pancreatitis has been found to be ex-tremely responsive to corticosteroid therapy in multiplereports and studies,6,13-15 although symptoms may recur.Improvement in the characteristic radiologic findings, in-cluding diffuse pancreatic enlargement, and reduction inserum IgG4 levels have been shown with corticosteroidtherapy.3,6,15 Secondary improvement in insulin secretionand glycemic control in patients with newly acquired orpreexisting diabetes has also been reported after adminis-tration of corticosteroids.13,14,16 The typical dosage of pred-nisone was 40 mg/d for 4 weeks and then 5 mg each weekthereafter before discontinuation.

Clinicians need to be aware of AIP and its close mimicryof pancreatic cancer. At the very least, AIP should beincluded in the differential diagnosis of patients whoseclinical presentation resembles pancreatic cancer. Carefulreview of clinical, radiologic, and serologic findings can besuggestive of AIP, with the cornerstone of diagnosis beinghistologic findings and immunostaining for IgG4.

Correct answers: 1. d, 2. b, 3. e, 4. c, 5. a

REFERENCES1. Bipat S, Phoa SS, van Delden OM, et al. Ultrasonography, computed

tomography and magnetic resonance imaging for diagnosis and determiningresectability of pancreatic adenocarcinoma: a meta-analysis. J Comput AssistTomogr. 2005;29(4):438-445.

2. Delbeke D, Pinson CW. Pancreatic tumors: role of imaging in the diag-nosis, staging, and treatment. J Hepatobiliary Pancreat Surg. 2004;11(1):4-10.

3. Sahani DV, Kalva SP, Farrell J, et al. Autoimmune pancreatitis: imagingfeatures. Radiology. 2004 Nov;233(2):345-352. Epub 2004 Sep 30.

4. Abraham SC, Wilentz RE, Yeo CJ, et al. Pancreaticoduodenectomy(Whipple resections) in patients without malignancy: are they all ‘chronicpancreatitis’? Am J Surg Pathol. 2003;27(1):110-120.

5. Hardacre JM, Iacobuzio-Donahue CA, Sohn TA, et al. Results ofpancreaticoduodenectomy for lymphoplasmacytic sclerosing pancreatitis. AnnSurg. 2003;237(6):853-859.

6. Hamano H, Kawa S, Horiuchi A, et al. High serum IgG4 concentrationsin patients with sclerosing pancreatitis. N Engl J Med. 2001;344(10):732-738.

7. Montefusco PP, Geiss AC, Bronzo RL, Randall S, Kahn E, McKinleyMJ. Sclerosing cholangitis, chronic pancreatitis, and Sjogren’s syndrome: asyndrome complex. Am J Surg. 1984;147(6):822-826.

8. Chari ST, Smyrk TC, Levy MJ, et al. Diagnosis of autoimmune pancre-atitis: the Mayo Clinic experience. Clin Gastroenterol Hepatol. 2006 Aug;4(8):1010-1016. Epub 2006 Jul 14.

9. Pearson RK, Longnecker DS, Chari ST, et al. Autoimmune pancreatitis:does it exist? Pancreas. 2003;27(1):1-13.

10. Okazaki K, Kawa S, Kamisawa T, et al. Clinical diagnostic criteria ofautoimmune pancreatitis: revised proposal. J Gastroenterol. 2006;41(7):626-631.

11. Deshpande V, Mino-Kenudson MM, Brugge WR, et al. Endoscopicultrasound guided fine needle aspiration biopsy of autoimmune pancreatitis:diagnostic criteria and pitfalls. Am J Surg Pathol. 2005;29(11):1464-1471.

12. Zamboni G, Luttges J, Capelli P, et al. Histopathological features ofdiagnostic and clinical relevance in autoimmune pancreatitis: a study on 53resection specimens and 9 biopsy specimens. Virchows Arch. 2004 Dec;445(6):552-563. Epub 2004 Oct 27.

13. Tanaka S, Kobayashi T, Nakanishi K, et al. Corticosteroid-responsivediabetes mellitus associated with autoimmune pancreatitis [letter]. Lancet.2000;356(9233):910-911.

14. Kamisawa T, Egawa N, Inokuma S, et al. Pancreatic endocrine andexocrine function and salivary gland function in autoimmune pancreatitisbefore and after steroid therapy. Pancreas. 2003;27(3):235-238.

15. Kamisawa T, Egawa N, Nakajima H, et al. Morphological changes aftersteroid therapy in autoimmune pancreatitis. Scand J Gastroenterol. 2004;39(11):1155-1158.

16. Tanaka S, Kobayashi T, Nakanishi K, et al. Evidence of primary β-celldestruction by T-cells and β-cell differentiation from pancreatic ductal cells indiabetes associated with active autoimmune chronic pancreatitis. DiabetesCare. 2001;24(9):1661-1667.