Autoimmune pancreatitis： Functional and morphological recovery after steroid therapy

Autoimmune pancreatitis, a recently recognized type of chronic pancreatitis, is not rare in Japan, but reports of it elsewhere are relatively uncommon. We report the first preoperatively diagnosed case of autoimmune pancreatitis in Hungary, which responded well to steroid treatment and provided radiographic and functional evidence of this improvement. A 62-year-old female presented with a 4-month history of recurrent epigastric pain and a 5-kg weight loss. The oral glucose tolerance test (OGTT) indicated diabetes mellitus and the result of the fecal elastase test was abnormal. Ultrasonography (US) and the CT scan demonstrated a diffusely enlarged pancreas, and endoscopic retrograde cholangiopancrea-tography (ERCP) an irregular main pancreatic duct with long strictures in the head and tail. Autoimmune pancreatitis was diagnosed. The patient was started on 32 mg prednisolone daily. After 4 wk, the OGTT and faecal elastase test results had normalized. The repeated US and CT scan revealed a marked improvement of the diffuse pancreatic swelling, while on repeated ERCP, the main pancreatic duct narrowing was seen to be ameliorated. It is important to be aware of this disease and its diagnosis, because AIP can clinically resemble pancreatobiliary malignancies, or chronic or acute pancreatitis. However, in contrast with chronic pancreatitis, its symptoms and morphologic and laboratory alterations are completely reversed by oral steroid therapy.     

Serum Adenosine Deaminase Levels in Pancreatic Diseases

Background: Adenosine deaminase (ADA) is found in most tissues including the pancreas. Its role in inflammation and malignancy has been studied experimentally. To date, serum ADA levels in pancreatic diseases have not been studied before. Aim: To assess the levels of ADA in patients with pancreatitis and cancer of the pancreas. Methodology: Serum levels of ADA were investigated in 14 cases with acute pancreatitis (mean age 46 years; male/female 5/9), 38 with chronic pancreatitis (mean age 46 years; male/female 25/13), 21 with cancer of the pancreas (mean age 67 years; male/female 11/10), and 21 healthy controls (mean age 40 years; male/female 11/10). The ADA levels were also compared among patients with pancreatic cancer with regard to tumor size and localization and the presence of métastases. Correlation analysis between ADA and CA 19.9 was also performed. Results: Serum ADA levels were 12.66 (9.54–20.72), 12.51 (8.88–26.64), 15.36 (10.20–21.05) and 9.39 (6.58–11.84) U/l in patients with acute pancreatitis, chronic pancreatitis, pancreatic cancer, and healthy controls, respectively. Serum ADA levels were significantly higher in acute and chronic pancreatitis, and pancreatic cancer patients compared to the control group (p < 0.05). Pancreatic cancer patients had significantly higher serum ADA levels when compared with acute and chronic pancreatitis cases (p < 0.05). The serum ADA levels were comparable according to tumor size and location and the presence of metastases. There was a linear correlation between serum ADA and CA 19-9 levels (p = 0.027, r = 0.552). Conclusions: Our data suggest that the ADA enzyme may play a role in inflammatory diseases of the pancreas. Serum ADA levels increase in pancreatic disorders especially in pancreatic cancer. It may be a serum marker for the diagnosis of pancreatic cancer.     

Serum pancreatic secretory trypsin inhibitor in pancreatic diseases

To elucidate the diagnostic significance of serum pancreatic secretory trypsin inhibitor (PSTI) in pancreatic diseases, organ distribution of PSTI and abnormalities in serum PSTI were studied. The pancreas showed the highest content of PSTI, which was five times that of the stomach and almost 40 times that of the other organs. Serum PSTI and amylase were elevated in eight patients with acute pancreatitis, 27 and 11 patients of 47 with chronic pancreatitis, 31 and 13 of 36 with pancreatic cancer, and 67 and 62 of 109 with non-pancreatic disease, respectively. PSTI levels were more sensitive to the presence of pancreatic disease than were amylase levels. The specificities in serum of healthy controls and patients with non-pancreatic disease were similar for PSTI and amylase (69% vs 71%). In chronic pancreatitis and pancreatic cancer patients the efficiency of the PSTI assay was higher (P < 0.02) than the amylase assay (67% vs 63% for pancreatitis and 71% vs 66% for cancer). The sensitivity and efficiency of serum PSTI assay in chronic pancreatic diseases were superior to those of amylase.     

Serum PABA and fluorescein in the course of Bz-Ty-PABA and pancreolauryl test as an index of exocrine pancreatic insufficiency

Forty-six subjects (20 chronic pancreatitis, 7 chronic liver disease, 7 recovered from acute pancreatitis, 2 Crohn's disease, and 10 healthy controls) classified by S-C test as having normal pancreatic function (26 subjects), or moderate (10 subjects) and severe (10 cases) pancreatic insufficiency, were given, on different days, 1 g of oral PABA or 348 mg of oral fluorescein dilaurate. At the 1st, 2nd, and 4th hours (PABA) and the 2nd, 4th, and 6th hours (fluorescein) serum samples were taken for assay. In the presence of severe exocrine pancreatic insufficiency, the sensitivity of the fluorescein serum levels was higher than that observed for the PABA (100% and 80%, respectively). On the contrary, in presence of moderate pancreatic insufficiency, both the urinary test (pancreolauryl and PABA) give a sensitivity higher than that found in the serum tests (30–40% and 10–30%, respectively). The parallel combination of both the serum or urinary tests does not significantly improve the sensitivity of the single test. These results suggest that the serum PABA and serum fluorescein tests can be valid choice when a prolonged urinary collection is difficult, i.e., in children and in elderly patients. However, the slight diagnostic gain does not justify the routine use of both urinary and serum tests.This work was partially supported by grant 84.00880.04 of the National Research Council (CNR), Italy.     

Evocative Test of Serum Pancreatic Enzymes to Bombesin in Chronic Pancreatitis

The levels of serum immunoreactive trypsinogen and P-isoamylase in response to Bombesin intravenous infusion were evaluated in 25 controls, 18 patients with documented chronic pancreatitis, and nine subjects with nonpancreatic gastroenterological diseases. Mean immunoreactive trypsinogen peak values were significantly higher in controls and gastroenterological diseases than in chronic pancreatitis, but there was marked overlap in individual values between the three groups. As for P-isoamylase, a statistical difference was detected only between mean peak concentrations of control versus chronic pancreatitis. Integrated responses for both enzymes did not result in a better discrimination between controls, chronic pancreatitis, and gastroenterological diseases. This study confirms that evocative tests are of limited value in the diagnosis of pancreatic disease.     

Plasma insulin in pancreatic disease

Pancreatic exocrine function tests and plasma insulin curves after a glucose load have been performed in 74 patients, 32 with no significant pancreatic disease, 31 with various disorders of the pancreas, and 11 with postmature diabetes mellitus.Exocrine function was impaired in all patients with chronic pancreatitis and chronic relapsing pancreatitis, whereas insulin production was defective in seven of 10 of those with chronic pancreatitis, and in one of seven with chronic relapsing pancreatitis. The findings in other examples of pancreatic disease are mentioned. Two out of four patients presenting with diabetes mellitus, who were found to have a flat plasma insulin curve, proved on investigation to have chronic pancreatitis.The results of plasma insulin response curves in this series are discussed in relation to pancreatic disease and their possible value in diagnosis.     

Differentiation of chronic pancreatitis from pancreatic cancer: recent advances in molecular diagnosis

Chronic pancreatitis is an inflammatory disease of the pancreas, characterized by a progressive destruction of the exocrine and endocrine pancreas, leading both to exocrine and endocrine insufficiency. In recent years, our knowledge of this disease has improved, an epidemiological link between chronic pancreatitis and pancreatic cancer has been established, and the molecular alterations underlying their pathogenesis have been partly revealed. Nevertheless, the differentiation of chronic inflammation of the pancreas from cancer of the pancreas remains a great challenge. This overview will point out the present knowledge of the molecular pathogenesis of chronic pancreatitis and pancreatic cancer and will focus on the role of molecular markers for differentiating chronic pancreatitis from pancreatic cancer.     

Autoimmune pancreatitis today: clinical features and diagnostic strategies

Autoimmune pancreatitis (AIP) is a particular form of chronic pancreatitis recognized as clinical entity only in recent decades. Peculiar clinical, serological, histological and radiological features make it different from other types of pancreatitis. The diagnosis of AIP represents a challenge for the clinicians. Particularly in its focal form, it shows several features in common with pancreatic adenocarcinoma. Both of these conditions, in fact, are often associated with obstructive jaundice, cause increase of the volume of the pancreas and can share the radiologic appearance of a focal mass. The autoimmune pancreatitis instead of pancreatic cancer regresses promptly after treatment with oral corticosteroids. Because of the different management of the two diseases a correct differential diagnosis is imperative. From 5% to 21% of AIP cases are diagnosed in patients after pancreatic resection performed for suspected malignancy. Still not identified a specific serological marker of AIP which can allow a definitive diagnosis of the disease. Both the diagnosis of pancreatic cancer as AIP is paid on the basis of different clinical tests: the diagnosis of pancreatic cancer requires imaging studies, laboratory tests and biopsy of the pancreas, while the diagnosis of AIP requires confirmation of the diagnostic histological, serological and radiological criteria, the involvement of other organs and a positive response to treatment with corticosteroids. Recently, three different diagnostic strategies for AIP have been proposed.     

An evaluation of 75Se Selenomethionine scanning as a test of pancreatic function compared with the secretin-pancreozymin test

The uptake of ⁷⁵Se Selenomethionine by the pancreas has been evaluated in 102 patients and compared with the secretin-pancreozymin test of pancreatic function. In groups of patients with chronic pancreatitis and cancer of the pancreas abnormal scans closely parallel the diminished exocrine secretion, especially bicarbonate output, following a submaximal dose of secretin. Thirty per cent of the group with no pancreatic abnormality have abnormal scans, though the secretinpancreozymin test is normal. Though a normal scan excludes the presence of chronic pancreatitis and cancer of the pancreas with a probability greater than 90%, an abnormal scan is found so frequently in normal subjects that it does not provide a reliable index of impaired pancreatic function.     

Rapid endoscopic secretin stimulation test and discrimination of chronic pancreatitis and pancreatic cancer from disease controls.

BACKGROUND & AIMS: The cholecystokinin (CCK)/secretin pancreatic function tests to diagnose pancreatic exocrine insufficiency are time consuming and invasive. Our aim was to develop a rapid pancreatic function test performed during upper endoscopy that could discriminate between patients with normal from impaired exocrine pancreatic secretion. METHODS: We prospectively evaluated 412 patients for possible pancreatic diseases. During upper endoscopy, 1 CU/kg of secretin was given intravenously and duodenal juice (collected for 10 min) was assayed for concentrations of bicarbonate and lipolytic and trypsin activity. Final diagnosis was by histology, imaging, and a previously validated scoring system (for chronic pancreatitis). Of 412 patients, 117 patients had normal pancreas, 72 patients had chronic pancreatitis, and 116 patients had pancreatic adenocarcinoma. The remaining 107 patients had miscellaneous disease of the peripancreatic region. In 28 patients we also validated the secretin test with the standard CCK pancreatic function test. RESULTS: There was no difference between bicarbonate or trypsin concentrations among the groups. Lipolytic concentration was significantly lower in chronic pancreatitis (115 +/- 18) and in pancreatic adenocarcinoma (87 +/- 10) compared with patients with normal pancreas (229 +/- 23; P < 0.03 and P < 0.0001, respectively). The overall accuracy of the endoscopic secretin test was 79%, with positive and negative predictive values of 73% and 85%, respectively. The concentration of lipolytic activity obtained by the endoscopic secretin test in 28 patients correlated moderately well (r = 0.41, P < 0.03) with lipolytic output obtained by the CCK pancreatic function test. CONCLUSIONS: Lipolytic concentration in duodenal juice after intravenous secretin collected for 10 minutes during upper endoscopy was significantly lower in chronic pancreatitis and pancreatic adenocarcinoma compared with patients with normal pancreas, but was not accurate enough for routine clinical use.     

Serum and correspondent tissue measurements of epidermal growth factor (EGF) and epidermal growth factor receptor (EGF-R)

Summary Background. EGF and EGF-R are frequently overexpressed in the tissue of patients suffering from ductal pancreatic cancer and to lesser degree in patients with chronic pancreatitis. The aim of this study was to determine the value of serum measurements in these patients to detect malignant pancreatic disease. In cases of pancreatic cancer, the tissue expression of EGF and EGF-R was evaluated by immunohistochemistry. Method. Thirty-five patients with chronic pancreatitis and 31 patients with pancreatic cancer were evaluated; 71 patients admitted for routine surgery (hernia repair, cholecystectomy, goiter surgery) served as controls. Results. EGF and EGF-R values were not significantly different in pancreatic cancer as compared to controls and did not correlate with other tumor markers (CA 19-9, carcinoembryonic antigen [CEA], tumor polypeptide antigen [TPA]) or with the stage of the disease. Fourteen patients (67%) with pancreatic cancer displayed tissue overexpression for EGF and 11 patients for EGF-R (52%). These patients, however, also failed to exhibit any significant pathological changes in serum concentration. In chronic pancreatitis, EGF and EGF-R were significantly decreased as compared to pancreatic cancer and controls. This was an unexpected finding. There was a positive correlation to clinical exocrine insufficiency. Conclusion. The results of this study show that routine measurements of epidermal growth factor (EGF) and epidermal growth factor receptor (EGF-R) cannot improve screening for pancreatic cancer despite the frequently present tissue overexpression. Both values fail to reveal this malignancy in a serum test. Patients with chronic pancreatitis exhibit no or very low concentrations of EGF. In cases where preoperative diagnosis is difficult the noninvasive EGF and EGF-R serum measurements may be helpful in discriminating between pancreatic cancer and chronic pancreatitis.     

Serum Markers and Clinical Data in Diagnosing Pancreatic Cancer: A Contrastive Approach

In order to assess the value of serum markers and simple clinical data in the differential diagnosis of pancreatic cancer, we studied 32 control subjects and 28 patients with pancreatic cancer, 26 with chronic pancreatitis, and 37 with extra-pancreatic diseases. CA 19-9 was found to be the best marker in detecting pancreatic cancer. Among the clinical data, presence and onset of pain attacks, age, and weight loss were selected as the most informative in assessing chronic pancreatic disease. Clinical data correctly classified 88.5% of chronic pancreatitis and 75.0% of pancreatic cancer; serum markers identified pancreatic tumor in 67.9% of the patients. The adjunct of serum markers to clinical data did not improve accuracy in diagnosing chronic pancreatic disease. Since clinical data and serum markers generally become positive at an advanced stage of the disease, early diagnosis of pancreatic cancer is a goal still to be attained.     

Comparison of the oral (PABA) pancreatic function test, the secretin-pancreozymin test and endoscopic retrograde pancreatography in chronic alcohol induced pancreatitis.

The oral (PABA) pancreatic function test (PFT), the secretin-pancreozymin test and endoscopic retrograde pancreatography (ERCP) have been carried out in 32 patients with suspected chronic alcohol induced pancreatitis (CAIP) in order to evaluate which, if any, test was most likely to confirm the provisional diagnosis. Thirty one patients had changes of minimal (n = 6) moderate (n = 7) or advanced (n = 18) chronic pancreatitis on pancreatography, whilst one patient had a pancreas divisum. Eight hour urinary PABA excretion was significantly reduced in patients with moderate and advanced structural changes (p less than 0.001) and correlated significantly with all parameters of the PFT, although eight patients with an abnormal pancreatogram and pancreatic function test had a normal PABA value. The PFT was abnormal in 23 patients, but normal in five patients with an abnormal pancreatogram and low PABA value. Most patients with minimal change pancreatitis had a normal PABA test and PFT. We conclude that pancreatography appears to be the most sensitive method for detecting chronic pancreatic damage and for confirming a clinical diagnosis of chronic alcohol induced pancreatitis. Both the PFT and PABA test are useful confirmatory tests and whilst the PFT is slightly more sensitive for assessing pancreatic exocrine function, the PABA test is well tolerated and simple to perform. It may therefore be the complementary investigation of choice for this group of patients.     

Limits of the evocative pancreatic function test in the diagnosis of low-grade pancreatitis

At a certain level of stimulation of the enzymatic secretions of the pancreas utilizing duodenal hormones and caerulein in normal subjects, the hourly urinary amylase output increases beyond normal values. Under these conditions, the so-called evocative pancreatic function test becomes unusable for the diagnosis of chronic pancreatitis in the early stages.     

Ethanol feeding aggravates morphological and biochemical parameters in experimental chronic pancreatitis

BACKGROUND AND AIMS: Instillation of trinitrobenzene sulfonic acid (TNBS) into the rat pancreatic ducts induces morphological changes resembling human chronic pancreatitis. In humans, alcoholism is commonly associated with chronic pancreatitis, but ethanol feeding fails to induce pancreatitis in experimental animals. We hypothesized that ethanol would manifest its pathogenetic effects on a duct-injured pancreas. METHODS: Chronic pancreatitis was induced in rats by instillation of TNBS into pancreatic ducts. Thereafter, rats were fed a normal chow diet with or without ethanol supplementation. Control rats received vehicle and a normal diet. A separate group of vehicle-treated rats were also fed with ethanol. At 2 and 4 weeks pancreata were excised and processed for morphological examination or for biochemical assays. From crude homogenates, protein and hydroxyproline were quantified. After sonication, homogenates were also assayed for amylase and DNA. An oral glucose tolerance test was performed on the fourth week. RESULTS: TNBS induced chronic fibrogenic pancreatitis that was associated with a reduction in pancreatic weight, DNA, protein and amylase as compared to control rats. Ethanol feeding to TNBS-treated animals slowed weight gain, increased fasting glucose and impaired glucose tolerance test. Larger areas of gland atrophy were observed with a striking disruption of the normal architecture of the islets. Ethanol accelerated pancreatic involution and collagen deposition as measured by total amylase, protein, DNA and hydroxyproline content. CONCLUSIONS: In TNBS chronic pancreatitis, active fibrogenesis is associated with progressive atrophy of glandular elements. Morphological and biochemical parameters are aggravated by sustained ethanol intake.     

Chronic obstructive pancreatitis due to a pancreatic cyst in a patient with autosomal dominant polycystic kidney disease

Background—Autosomal dominant polycystic kidneydisease, the most frequent inherited polycystic disease, is a systemicdisorder characterised by the development of numerous and bilateralkidney cysts leading to chronic renal failure. Extrarenal cysts arelocated mainly in the liver but also in various organs including thepancreas. To our knowledge, complications of pancreatic cysts in thisdisease have never been reported.
Patient—The first case of painful chronicobstructive pancreatitis due to a true pancreatic cyst in a patientwith autosomal dominant polycystic kidney disease is reported.Abdominal transparietal and endoscopic ultrasonography, computedtomography, and endoscopic retrograde cholangiopancreatography showed acystic lesion in the body of the pancreas associated with upstreamdilatation of the main pancreatic duct. Intraoperative ultrasonographybefore and after cyst fluid aspiration, and pancreatography andpathological examination of the resected distal pancreas confirmed thatboth main pancreatic duct enlargement and chronic pancreatitis were caused by a benign cyst.
Conclusion—Chronic obstructive pancreatitisshould be added to the extrarenal complications of autosomal dominantpolycystic kidney disease.

Keywords:chronic obstructive pancreatitis; pancreatic cyst; autosomal dominant polycystic kidney disease; distal pancreatectomy

     

Exocrine and endocrine functional reserve in the course of chronic pancreatitis as studied by maximal stimulation tests

Thirty patients suffering from chronic alcoholic pancreatitis (18 calcified) were entered into a study of exocrine and endocrine pancreatic function based on two maximal stimulation tests, namely the secretin-cerulein test and the glucagon test with serum assays of C peptide. The glucagon test was also performed in 19 control subjects. In addition, 10 chronic pancreatitis patients and nine controls were subjected to an oral glucose tolerance test (OGTT) with serum insulin determinations. C peptide basal values were decreased only in patients with severe pancreatic exocrine insufficiency (P less than 0.001), while delta C peptide values were also reduced in patients with moderate exocrine insufficiency (P less than 0.001). Lipase output correlated very well with delta C peptide values (P less than 0.001). While serum insulin levels during OGTT and C peptide basal values showed no significant differences between the chronic pancreatitis and control groups, delta C peptide values were significantly reduced in chronic pancreatitis patients (P less than 0.02). Both endocrine and exocrine function are impaired in chronic pancreatitis, as demonstrated by maximal tests, even in early stages of the disease.     

Argyrophilic Nucleolar Organizer Regions May Help the Differential Diagnostic Distinction between Chronic Pancreatitis and Pancreatic Ductal Adenocarcinoma

Mäkinen K, Eskelinen M, Lipponen P, Pasanen P, Nuutinen P, Alhava E. Argyrophilic nucleolar organizer regions may help the differential diagnostic distinction between chronic pancreatitis and pancreatic ductal adenocarcinoma. Scand J Gastroenterol 1994;29:1029-1033.

Background: The aim of this study was to determine whether the number of argyrophilic nucleolar organizer regions (AgNORs) could be of diagnostic significance in differentiating between chronic pancreatitis and pancreatic ductal adenocarcinoma.

Methods: The number of AgNORs was enumerated in biopsy specimens of normal pancreas, chronic pancreatitis, and pancreatic ductal adenocarcinoma.

Results: The number of AgNORs was lower in patients with normal pancreas than in patients with chronic pancreatitis or pancreatic adenocarcinoma. In addition, the number of AgNORs was significantly lower in chronic pancreatitis than in pancreatic ductal adenocarcinoma (p < 0.001).

Conclusions: The diagnosis of pancreatic adenocarcinoma is usually clear. Difficulties can be encountered, however, in cases of chronic pancreatitis, specially when biopsy material is small. Our results suggest that the number of AgNORs may help in distinguishing between chronic pancreatitis and pancreatic ductal adenocarcinoma, especially in diagnostically difficult specimens.     

Diagnosis of pancreatic cancer by cytology and measurement of oncogene and tumor markers in pure pancreatic juice aspirated by endoscopy

BACKGROUND/AIMS: Cytological examination of pancreatic juice is useful in the diagnosis of an occult cancer of the pancreas. The early diagnosis of pancreatic carcinoma using traditional radiographic or ultrasonographic methods is extremely difficult. METHODOLOGY: In order to detect an early pancreatic cancer, cytological examination, measurement of tumor marker, and detection of K-ras point mutation were performed using the samples of pure pancreatic juice aspirated endoscopically in patients who had symptoms or findings that suggested pancreatic disease. RESULTS: By routine ERP-cytology, positive cytologic results were obtained in 15 (4%) out of 359 patients without a mass. With the aid of intra-operative cytodiagnosis, all 15 occult neoplasms of the pancreas were successfully resected. One patient died from another disease without evidence of recurrence. However, the other patients were alive with no evidence of recurrence for an average of 5.5 years following surgery. The patients who had negative ERP-cytology results were observed, but no further cases of pancreatic cancer were found. The CEA levels in the pure pancreatic juice were significantly higher in patients with pancreatic cancer than in those with pancreatitis. K-ras point mutation at codon 12 was detected not only in cases of pancreatic cancer, but also in cases of chronic pancreatitis as well as control subjects. CONCLUSIONS: Cytological examination of pancreatic juice is useful in the diagnosis of an early and potentially curable in situ cancer of the pancreas. The CEA levels in the pure pancreatic juice provided useful information for differentiating the pancreatic cancer from chronic pancreatitis. K-ras point mutation at codon 12 in pancreatic juice was considered to be useful in identifying patients at high risk for the development of pancreatic cancer.