Nonalcoholic Chronic Pancreatitis Research Articles

“Human Pancreas-Specific Protein” (Procarboxypeptidase B)

Human pancreas-specific protein (PASP) has been characterized previously as a serum marker for pancreatitis. It was then identified as pancreatic procarboxypeptidase B (PCB). The aim of the present study was to verify the usefulness of PASP (PCB) as a serum marker in patients with acute (n = 20) and chronic (n = 12) pancreatitis and in those following endoscopic retrograde cholangiopancreaticography (ERCP) (n = 44). Serum PASP values were analyzed by radioimmunoassay, with a range of normal values between 15 and 111 ng/ml. Between April 1992 and September 1992, 20 subjects (19-86 years of age) with acute pancreatitis (alcoholic, 8; biliary, 8; other, 4) were studied. We found edematous pancreatitis in 17 cases and severe hemorrhagic pancreatitis in three cases. At admission, peak levels of PASP (average value, 1,976 +/- 329 ng/ml), pancreatic isoamylase (942 +/- 151 U/L) and lipase (2,946 +/- 534 U/L) were detected in 15 of 20, 16 of 20, and 12 of 20 cases, respectively. The etiology of the pancreatitis had no influence on the PASP values. Furthermore, 10 patients with alcoholic and two patients with nonalcoholic chronic pancreatitis (29-67 years of age) were studied. The average peak level of PASP was 1,229 +/- 434 ng/ml. In this group, PASP paralleled the time course of amylase and lipase. Maximal PASP, amylase, and lipase levels were found in 11 of 12, nine of 12, and five of 12 patients, respectively, on the day of admission. ERCP was performed in 44 patients (36-87 years of age), demonstrating common bile duct stones in 16 and bile or pancreatic ductal tumors in 15 cases.(ABSTRACT TRUNCATED AT 250 WORDS)

Nonalcoholic Chronic Pancreatitis with Pancreatic Calcification: Presenting Manifestation of Occult Celiac Disease

A 62-year-old Canadian Caucasian female with nonalcoholic chronic pancreatitis, diabetes, exocrine failure and pancreatic calcification presented with weight loss, diarrhea and peripheral edema. Subsequent investigations revealed celiac disease that was responsive to a gluten-free diet. Calcification in the pancreas may reflect impaired absorption with severe protein-energy malnutrition and may be the initial presenting feature of occult celiac disease.

Abdominal radiotherapy is a cause for chronic pancreatitis

We report a series of five patients with nonalcoholic chronic pancreatitis who underwent abdominal radiotherapy for Hodgkin's disease (n = 4) or seminoma (n = 1) at doses ranging from 3600 to 4050 rads, 6 to 20 years (median, 7 years) before the onset of pancreatitis. Patients were in complete remission for their malignant disease. Other causes of chronic pancreatitis were excluded. The manifestations of chronic pancreatitis (median follow-up after the diagnosis of pancreatitis, 5 years) were pancreatic pain (n = 5), acute pancreatitis (n = 3), pseudocysts (n = 3), common bile duct stenosis (n = 2), duodenal stenosis (n = 1), splenic vein obstruction (n = 1), diabetes mellitus (n = 4), steatorrhea (n = 4), and pancreatic calcifications (n = 1). Other abdominal radiation injuries were severe chronic ulcer of the genu superius (n = 1), stenosis at the junction of the right and left hepatic ducts (n = 1), and splenic and left renal atrophy (n = 1). In one patient, pathological examination of the pancreas showed signs of chronic pancreatitis, severe fibrous endarteritis, and lack of inflammation. Abdominal radiotherapy should be added to the list of causes of chronic pancreatitis. We suggest that the physiopathology of postradiotherapy chronic pancreatitis is a vascular process.

Histological study of alcoholic, nonalcoholic, and obstructive chronic pancreatitis.

Pancreatic tissue obtained from 26 patients with alcoholic chronic pancreatitis (ACP), nine patients with nonalcoholic idiopathic chronic pancreatitis (NAICP), and seven patients with obstructive chronic pancreatitis (OCP) was studied in an attempt to determine whether clinical or etiologic differences have a morphologic counterpart. Histologically it was easy to distinguish ACP from OCP occurring distal to an obstruction of the pancreatic duct. Nine patients with NAICP showed histological features similar to those found in ACP. Plugs and calcifications were found as frequently in NAICP as in ACP, suggesting that NAICP, whatever the etiology, is truly pancreatolithiasis, which leads to slowly progressive fibrosis and acinar atrophy in the obstructed pancreatic lobule. Nerve fibers were found to be more numerous in all disease categories. Inflammatory foci of lymphocytes associated with nerves were observed in 57 and 35% of cases with OCP and ACP, respectively, but only in one patient with NAICP. These findings may constitute a pathological basis for the existing clinical data showing that NAICP frequently runs a pain-free course.

Etiology and natural history of chronic pancreatitis.

Chronic pancreatitis (CP) is a rare but serious disease with high morbidity and mortality. Its exact etiology remains uncertain, but several associated conditions have been identified. Geographical distribution of CP can be linked to alcoholism, especially in countries with high-protein, high-fat diets. In Afro-Asiatic countries with protein malnutrition, however, CP is frequently observed in children and young nonalcoholic adults from the poorest segments of these societies. To analyze the natural history of CP, besides etiology three additional main factors have to be considered, namely clinical pattern and therapy (surgery), pancreatic function (endocrine and exocrine), and morphology. During progress of the disease clinical picture, morphology and pancreatic function have typical correlative changes. Basically, from this viewpoint, three typical models of the disease can be distinguished: (1) early stage of uncomplicated CP; (2) late stage of uncomplicated CP, and (3) complicated CP, a disease stage which is characterised by local complications (chiefly pseudocysts and duct obstruction). The main concept of the natural history of CP bases on the thesis that CP burns itself out with spontaneous relief of pain, i.e. persistent freedom from pain occurs parallel with severe pancreatic dysfunction in the late stage of the disease. In the clinical picture and long-term course, nonalcoholic CP differs in certain essential respects from alcoholic CP; however, the two forms do not differ essentially as regards mortality and survival.

慢性膵炎の経過と予後に関する研究

To investigate complications, prognosis and prognostic factors for chronic pancreatitis (CP), 170 patients with CP (112 with alcoholic CP, nine with biliary CP and 49 with idiopathic CP) were followed up.Pancreatic pseudocysts were found in 29 patients with CP, biliary stenosis in 20 patients, and a peptic ulcer in 26 patients. Determination of whether the abdominal pain is caused by acute exacerbation of CP or by the peptic ulcer is important, because abdominal pain due to peptic ulcer is easily relieved by administration of H2-receptor antagonist. Mild liver damage or chronic hepatitis was observed in 26 patients with CP; and liver cirrhosis in nine. Duodenal stenosis was found in two patients.Thirty-nine patients with CP died during the follow-up period. Patients with alcoholic CP were significantly younger than those with nonalcoholic CP at the time of death. Thirteen patients died from malignancy which was the most frequent cause of deaths. Sudden deaths were observed in seven patients. Six patients died from pneumonia which was refractory to the intensive medical treatment. Three patients died from diabetic renal failure and three from heart failure.The observed number of CP was significantly higher than the expected number for the sex-age-matched general population in total deaths and cancer deaths. A similar finding was obtained in alcoholic CP. Alcoholic CP showed poorer prognosis than nonalcoholic CP. Contributing factors to the prognosis were age at the time of diagnosis, diabetes, smoking habit, outcome of pain, years at diagnosis in alcoholic CP, whereas they were age at diagnosis, smoking habit and diabetes in nonalcoholic CP. This indicates that abstinence, quitting smoking, and careful treatment for diabetes are important for improving the prognosis of CP.

慢性膵炎の経過と予後に関する研究

To investigate the relief of pain, quality of life and treatment of chronic pancreatitis (CP), 112 patients with alcoholic CP, nine with biliary CP and 49 with idiopathic CP were followed up.Partial or complete relief of pain was obtained in 64 patients with alcoholic CP (66%), nine with biliary CP (100%) and 29 with idiopathic CP (88%). Alcoholic CP showed a significantly lower ratio of pain relief than nonalcoholic CP. A long follow-up period (≥6 years) revealed greater pain relief. Patients with discontinued or decreased intake of alcohol showed a significantly higher ratio of pain relief than those continuing drinking. These findings indicate that factors contributing to pain relief are etiological category of CP, drinking habit after diagnosis and length of the follow-up period.Deterioration in quality of life was observed in 42 patients with alcoholic CP, one with biliary CP and 13 with idiopathic CP. Main causes for the deterioration in quality of life were pain, diabetes and loss of interest in work. Abstinence is important for patients with CP to maintain their quality of life.Endoscopic removal of protein plug contributed to pain relief. Surgical treatment was done in 54 patients with CP. Pain relief was observed in 41 operated patients, and deterioration in the quality of life in 17. Abstinence was important for operated patients as well as nonoperated patients to obtain pain relief and maintain the quality of life. Clinically overt steatorrhea was observed in two patients with CP, which was improved by a large dose of enzyme replacement therapy. Aggravation of diabetes had been observed, and number of patients dependent on insulin therapy increased during the follow-up period. Diabetes must be treated carefully because diabetes is an important factor contributing to the prognosis of CP.

Chronic Pancreatitis in the Elderly

Idiopathic senile chronic pancreatitis (CP) appears to be a special subtype of nonalcoholic CP. Main clinical features are onset after the age of 50 years, prevalence in men, a painless clinical course, marked weight loss associated with diarrhea (steatorrhea) or diabetes mellitus, and pancreatic calcific deposits. Idiopathic senile CP constitutes about two thirds of cases of nonalcoholic CP, but it is rare compared with the incidence of alcoholic CP. The relationship of idiopathic senile CP to the "normal" age-related morphologic and functional abnormalities of the exocrine pancreas is unknown.

Prognosis and prognostic factors in chronic pancreatitis.

To evaluate the prognosis and prognostic factors of chronic pancreatitis, 84 patients with alcoholic chronic pancreatitis and 51 with nonalcoholic chronic pancreatitis have been followed for 1-21 years (average of 7.1 years). The follow-up period was defined as the period from diagnosis to death in those who died and to the present in those still alive. The following conclusions were obtained. (1) Patients with alcoholic chronic pancreatitis showed a significantly higher mortality rate (26.2%) and cancer death rate (8.3%) than the age- and sex-matched population. In patients with nonalcoholic chronic pancreatitis, however, the difference did not reach the level of statistical significance, although both rates tended to be higher. (2) Patients with alcoholic chronic pancreatitis showed a significantly poorer prognosis than those with nonalcoholic chronic pancreatitis. (3) Frequent causes of death in chronic pancreatitis were cancer (11 cases) and diabetes-associated conditions (renal failure in three cases, intractable pneumonia in one, hypoglycemic shock in two, and myocardial infarction in two). Death directly from pancreatitis was observed in four. (4) Unfavorable prognostic factors in alcoholic chronic pancreatitis included heavy drinking, continuance of drinking after diagnosis, smoking, insulin-dependent diabetes, and an advanced age. In nonalcoholic chronic pancreatitis, however, patients' age was the only significant prognostic factor; smoking did not reach the level of statistical significance, although it tended to lead to a poorer prognosis.

Evolution and regression of pancreatic calcification in chronic pancreatitis: A prospective long-term study of 107 patients

Pancreatic calcifications are virtually pathognomonic of chronic pancreatitis and develop in up to 90% of patients with alcoholic chronic pancreatitis in series with long-term results. We investigated the natural course of pancreatic calcification in a prospective longitudinal study over the past 23 yr. All patients were studied at regular intervals with particular regard to etiology, clinical findings, surgery, pancreatic function, and pancreatic calcification visible by x-ray (e.g., film series in three projections centered on the pancreas). We evaluated the findings of 107 patients with x-ray documentation of pancreatic calcification in at least three film series over a period of 4 yr or longer. Eighty-four patients had alcoholic chronic pancreatitis (group A) and 23 patients had nonalcoholic chronic pancreatitis (group B). Four hundred seventy-two film series of group A and one hundred forty-two film series of group B were reviewed independently by two expert teams. Both series were graded according to a score system in terms of intensity and distribution of pancreatic calcification (correlation of grading r = 0.91). The duration of calcification averaged 10 yr in group A and 12.6 yr in group B. Similar dynamic changes of pancreatic calcification were noted in groups A and B. Chronologically, three phases of evolution could be distinguished. After an initial increase (phase 1), >50% of cases reached a plateau of stationary calcification (phase 2). Approximately one-third of cases showed a marked decrease of calcification in late phases of chronic pancreatitis (phase 3). Dissolution of pancreatic stones was related primarily to duration of chronic pancreatitis (duration of calcification and marked pancreatic dysfunction), and occurred frequently (but not exclusively) in patients after ductal drainage procedures. These results indicate that spontaneous dissolution of pancreatic stones is a rather common biologic phenomenon. The factors responsible for dissolution of stones remain to be elucidated.

Chronic pancreatitis, HLA and autoimmunity

HLA-A and B antigens were studied in 88 Caucasoids with chronic pancreatitis resident in the Manchester area. In the subgroup of 52 patients with alcohol-related chronic pancreatitis HLA-B21 was significantly increased in frequency compared with 344 local controls (Pc = 0.0128). In the non-alcoholic sub-group of 36 patients, the incidence of HLA-A1 was significantly higher than in controls (Pc = 0.0021); whilst HLA-B8 was present in 38.8% of patients and 27.9% of controls. When these data are amalgamated with data from Lyon (France), the antigen HLA-A1 is significantly associated with non-alcoholic chronic pancreatitis.

Differences in the (Nonalcoholic) and Natural History of Idiopathic Alcoholic Chronic Pancreatitis. A Comparative Long-Term Study of 287 Patients

Controversies in the literature regarding definition, diagnosis, and therapy of chronic pancreatitis may be related in part to differences in the natural history of alcoholic and idiopathic (nonalcoholic) chronic pancreatitis. In order to evaluate this problem the long-term course of 205 patients with alcoholic (85.4% with calcifications) (group A) and 82 patients with idiopathic (nonalcoholic) chronic pancreatitis (76.8% with calcifications) (group B) has been analyzed prospectively since 1963. The patients were studied at regular intervals with particular regard to pain, pancreatic exocrine, and endocrine function and calcifications. The observation time was 2 years or longer in 230 patients with a median observation time of 6.7 years from diagnosis in group A and 10.6 years in group B. In group B over 50% of the cases had primary painless chronic pancreatitis. Progressive deterioration of exocrine and endocrine function was observed in both groups. However, in group A the rate of progression of exocrine dysfunction after diagnosis was more rapid and the incidence of diabetes in relation to marked exocrine insufficiency was much higher than in group B. Steatorrhea preceded diabetes in 56% (group A) and 80% (group B), respectively. Onset of pancreatic calcifications was closely associated with pancreatic exocrine insufficiency in group A in contrast to group B. In addition lasting pain relief occurred spontaneously in about 30% of patients in group B despite a normal exocrine function for 6 years or longer which is in disaccord with the results in alcoholic chronic pancreatitis. In conclusion group A and B have many features in common, in particular the high incidence of pancreatic calcifications and the progressive pancreatic dysfunction. However, the long-term profile of both groups differs in some important aspects, particularly in the clinical pattern and in the rate of progression of pancreatic dysfunction and morphology. These differences should be appreciated in the discussion of problems regarding definition, diagnosis, and surgical therapy of chronic pancreatitis.

A Study of Chronic Pancreatitis by Serial Endoscopic Pancreatography

The pancreatic duct system was studied with repeated endoscopic retrograde pancreatography in 31 patients with chronic pancreatitis, 32 patients with suspected chronic pancreatitis, and 16 controls without pancreatic disease. In chronic alcoholic pancreatitis the pancreatograms showed marked changes during the initial examination with progression even after abstinence or reduction of drinking. In the alcoholics with suspected chronic pancreatitis, progressive lesions in branch ducts with almost intact main ducts were recognized. In contrast, no remarkable alterations on serial pancreatograms were observed in nonalcoholic cases with definite or suspected chronic pancreatitis. These results suggest that pancreatic duct lesions play an important role in the development and progression of chronic alcoholic pancreatitis in contrast to chronic nonalcoholic pancreatitis.

Studies on pancreatic duct system

Three-dimensional reconstruction of pancreatic ducts were made from specimens of pancreases from chronic pancreatic injury dogs following adjuvant injection, one patient with chronic non-alcoholic pancreatitis, and 2 patients with chronic alcoholic pancreatitis. The ductal alterations of alcoholic pancreatitis showed more apparent changes than those of non-alcoholic pancreatitis. The lesions in experiment such as uneven surface, irregular dilatation, tortuosity, and anastomosis, resembled to those of alocholic calcifying pancreatitis. Although gross appearance of the reconstructed ducts in advanced cases of experimental pancreatic injury revealed some resemblance to that of alcoholic calcifying pancreatitis, histologically, the epithelial changes of the former were different from those of the latter. Thus we concluded that more complicated factors than those considered in experiment play a role in combination in the pathogenesis of bead-like dilatation of the pancreatic ducts of chronic pancreatitis.

A Clinical investigation of chronic pancreatitis

An analysis of 89 cases with chronic pancreatitis revealed 56% of chronic alcoholic pancreatitis (AP). The sex ratio was 47 males to 3 females and the mean age at onset was 42.4 years in AP and 49.3 years in chronic non-alcoholic pancreatitis (NAP). The 'total amount' of alcohol consumption was correlated to the onset. In AP, the abdominal pain was apt to relapse and severe in nature, furthermore painless pancreatitis was seen in 6%. The association with diabetes or calcification (38%) were more frequently seen in AP. The calcifications in AP appeared to be smaller in size and distributed diffusely or localized in cephalic portion. A striking frequency of liver dysfunctions (39 cases) were demonstrated, however, cirrhosis was rare in AP. The P-S test dysunctions in NAP were frequently reversible in the follow up study, while even some of chronic asymptomatic alcoholics developed clinical signs of pancreatitis during the observed period and proceeded to definite AP, of whom pancreatic dysfunctions showed fluctuation and eventual progression. In other words, even pain free intervals the pancreatic inflammation in susceptible persons may proceed to ultimated destruction of the pancreas. The fatality from chronic pancreatitis was rare (12.3%), which was related diabetes mellitus.