J. Otto

Natural course in chronic pancreatitis : pain, exocrine and endocrine pancreatic insufficiency and prognosis of the disease

The natural course of the classical symptoms of chronic pancreatitis, i.e. pain, exocrine and endocrine pancreatic insufficiency, was followed up in 335 patients over a median of 9.8 years (mean 11.3 +/- 8.3 years). Pain relief was not obtained in the majority of patients, even after a longterm observation of > 10 years, and severe exocrine and/or endocrine insufficiency, severe duct abnormalities and pancreatic calcifications developed. Alcohol abstinence failed to have a significant beneficial effect on pain. Pancreatic surgery led to pain relief immediately after operation, but later on the pain course between operated and nonoperated patients was not significantly different. Repeated exocrine pancreatic function tests in 143 patients showed that functional exocrine impairment came to a standstill (46%), or improved (11%). At the end of the observation, 22% of 335 patients still had normal endocrine function and only 40% required insulin treatment. Alcohol abstinence had a significant beneficial effect on endocrine, but not on exocrine pancreatic insufficiency. Chronic pancreatitis led to a sharp increase in unemployment and retirement. Pancreatic carcinoma occurred in 3% and extrapancreatic carcinoma in 4%. The mortality rate within the observation period was 22%, pancreatitis-induced complications accounted for 13% of these deaths.

Exocrine Pancreatic Function in Insulin-Dependent Diabetes mellitus

Exocrine pancreatic function was studied in patients with long-standing insulin-dependent diabetes mellitus using the secretin-pancreozymin test (n = 53), and estimation of immunoreactive trypsin (n = 43) and pancreatic isoamylase (n = 43). The secretin-pancreozymin test was abnormal in 23 patients (43%). The abnormalities found were a decreased output of lipase (37%), amylase (36%) or trypsin (26%) and bicarbonate (15%). Serum immunoreactive trypsin was below normal in only 6 (14%) and pancreatic isoamylase in 29 (67%) patients. There was no correlation between impairment of the secretin-pancreozymin test and decreased serum enzyme levels. It is concluded that an impairment of exocrine pancreatic function is frequent in insulin-dependent diabetics but that a decrease in serum enzymes, especially in pancreatic isoamylase, does not reflect an impairment of pancreatic function in these patients.

Pancreolauryl test. Evaluation of a tubeless pancreatic function test in comparison with other indirect and direct tests for exocrine pancreatic function.

The sensitivity and specificity of the pancreolauryl test was evaluated in comparison with the NBT-PABA test, the estimation of fecal chymotrypsin and fat, and the secretinpancreozymin test in 168 patients with and without pancreatic disease. The overall sensitivity rate was as follows: pancreolauryl test 90%, NBT-PABA test 86%, fecal chymotrypsin 66%. In patients with pancreatic steatorrhea the sensitivity of the pancreolauryl test was 100%, the NBT-PABA test 97%, and the fecal chymotrypsin estimation 92%. The specificity of these tests was: pancreolauryl test 97.6%, fecal chymotrypsin 87%, and NBT-PABA test 81.8%. The pancreolauryl test may be recommended as a noninvasive easy-to-perform tubeless pancreatic function test with a sufficiently high sensitivity and specificity.

The course of pain is the same in alcohol- and nonalcohol-induced chronic pancreatitis

The natural course of pain in chronic pancreatitis was followed up in 318 patients over 10.6 ± 8.0 years (median, 9.0 years). By the end of our follow-up, a significant decline in pain in alcoholics (n = 228) and nonalcoholics (n = 90) (p < 0.001 and p < 0.03) was marred by the fact that, even after more than 10 years, 50% of alcoholics and 62% of nonalcoholics still reported pain attacks (difference insignificant). Only alcoholics had pain relief with increasing exocrine pancreatic insufficiency (p < 0.02), but 54% of alcoholics and 73% of nonalcoholics still had pain attacks despite severe, enzyme substitution-requiring exocrine pancreatic insufficiency. The development of severe endocrine pancreatic insufficiency did not significantly influence the course of pain. It is concluded that no clinically relevant differences exist in the course of pain in alcoholic and nonalcoholic chronic pancreatitis.

Secretin-pancreozymin test (SPT) and endoscopic retrograde cholangiopancreatography (ERCP) : both are necessary for diagnosing or excluding chronic pancreatitis

Results of the SPT and the ERCP staged for their severity were compared in 202 patients. The correlation between both investigations was significant (p < 0.001); however, ERCP showed significantly more severe changes (p = 0.04). Furthermore, we found that 129 (64%) patients had parallel SPT and ERCP results, matching in all four gradings of severity. Forty-three (21%) patients had abnormal results for both SPT and ERCP, but the severity gradings did not parallel. Finally, 30 (15%) patients showed totally nonparallel results, a normal SPT and abnormal ERCP, or vice versa. Abnormal ERCP but normal SPT results were found in 23 of these 30 patients (group 1), and normal ERCP but abnormal SPT results in the seven remaining cases (group 2). In the first group, more patients had a history of acute pancreatitis compared to the second group (19 vs. one, p < 0.005). Based on medical history, laboratory and functional test results, and other morphological tests, chronic pancreatitis was diagnosed in two of 23 patients in group 1 and in all seven patients in group 2. Follow-up interviews (86 ± 54 months) were possible in 20 of the remaining 21 patients in group 1 and showed definite chronic pancreatitis in one and probable chronic pancreatitis in another two of them, whereas in the other 17 patients no symptoms of acute pancreatitis or abdominal pain suggestive of chronic pancreatitis had occurred. In conclusion, both SPT and ERCP should be used to complement each other when chronic pancreatitis is suspected. ERCP seems to over-diagnose the disease since duct changes may only reflect scars after severe acute pancreatitis, or old age, and are not necessarily a sign of chronic pancreatitis. SPT seems to diagnose chronic pancreatitis with more reliability.

Recovery of the pancreas after acute pancreatitis is not necessarily complete

SummaryIn 38 patients, exocrine pancreatic function was tested by means of the secretin-pancreozymin test (SPT) and pancreatic duct system with endoscopic retrograde cholangiopancreatography (ERCP) 34±36 mo (mean±SD, range 1–156 mo) following acute pancreatitis. SPT and ERCP results were both normal in 19 (50%). They were both abnormal in four (11%) patients (group 1). Fourteen (37%) patients with normal SPT had abnormal ERCP test results (group 2), and one (3%) patient with normal ERCP had abnormal SPT (group 3). All patients except one of group 2 could be followed up within a mean observation time of 105±46 mo (range 24–168 mo): Chronic pancreatitis developed in all four patients of group 1, in one patients of group 2, and in the single patient of group 3, and suspected chronic pancreatitis in another patient of group 2. Elevens of the remaining 12 patients with abnormal ERCP results, but normal exocrine pancreatic function (group 2), showed no signs or symptoms of acute or chronic pancreatitis. It is concluded that (1) recovery to normal does not necessarily occur after acute pancreatitis, (2) progression to chronic pancreatitis is possible at a considerable percentage, and (3) duct changes demonstrated by ERCP may persist without any later signs and symptoms of acute or chronic pancreatitis.

Pancreatic Calcifications: No Indicator of Severe Exocrine Pancreatic Insufficiency

Pancreatic calcifications are believed to occur only in advanced stages of exocrine pancreatic insufficiency. This belief has been reevaluated by correlating the results of the secretin-pancreozymin test, fecal fat analysis, and the presence of pancreatic calcifications on plain abdominal x-rays in 79 patients with chronic pancreatitis. Exocrine pancreatic insufficiency was classified as slight, moderate, or severe according to the results of the function tests, and pancreatic calcifications were assessed semi-quantitatively (grades 1-3) by an independent examiner. The results showed that severe exocrine pancreatic insufficiency did occur even in the absence of calcifications. Calcifications were more frequently detected with increasing severity of exocrine pancreatic insufficiency. The qualitative demonstration of pancreatic calcification was, however, not an indicator of severe, decompensated exocrine pancreatic insufficiency (50% false-positive results). It is concluded that pancreatic calcification is not necessarily an indicator of severe exocrine pancreatic insufficiency, and vice versa. Comparison between the results of tests for endocrine pancreatic function and plain abdominal x-ray showed such similarity that it can also be concluded that pancreatic calcifications are no indication of abnormal endocrine function, and vice versa.

When should treatment of acute experimental pancreatitis be started? The early phase of bile-induced acute pancreatitis.

SummarySodium taurocholate pancreatitis in the rat is a frequently used experimental model for evaluating therapeutical regimes in this disease. It is, however, uncertain when treatment should be started, as the early phase of this experimental model and thus the time when the pancreatitis really develops is unknown. Serum and pancreatic enzymes, as well as pancreatic morphology, were therefore studied 5, 30, and 60min after induction of sodium taurocholate pancreatitis. It was found that increase in serum enzymes and decrease in pancreatic enzymes and morphological changes characteristic for acute pancreatitis develop as early as 5 and 30 min after induction of pancreatitis. Thus, therapy in this model may be started shortly after induction of acute pancreatitis.

Effect of FOY-305 (camostate) on severe acute pancreatitis in two experimental animal models

Two models of severe acute pancreatitis were chosen and pancreatitis induced by sodium taurocholate and by a choline-deficient ethionine-supplemented diet, to evaluate the effectiveness of FOY-305 (camostate), a new synthetic trypsin inhibitor. Prophylactic administration of FOY-305 had a significantly favorable effect on the course of the sodium taurocholate-induced disease and on the survival rate of the treated group. A beneficial effect on the amylase and lipase content in serum and ascites was found, but no effect was observed on enzyme concentration in pancreatic tissue or on the degree of histologically detectable organ destruction. Therapeutic administration of FOY-305 had a significantly positive influence when infused directly, 5 and 30 min after the operation, whereas enzyme increase and organ destruction remained unaffected. FOY-305 showed a beneficial effect when given prophylactically or therapeutically at the beginning of the pancreatitis induced by a CDE diet, with no significant change in enzyme increase and degree of organ destruction. The favorable effect on survival time and rate in the early phase of these two severe experimental forms of pancreatitis may justify an evaluation of FOY-305 in a clinically controlled study.

Evaluation of Methaemalbumin in Acute Pancreatitis

Methaemalbumin (MHA) was measured in 62 patients with acute pancreatitis. In 26 MHA-positive patients the occurrence of renal and pulmonary complications was 65% and 58%, respectively, compared with 3% and 6% in 36 MHA-negative patients. Fatality rate was 54% in MHA-positive and 6% in MHA-negative patients. In 17 MHA-positive cases haemorrhagic pancreatitis was proven at laparotomy or postmortem examination. Thus MHA determination proved to be a valuable diagnostic and prognostic parameter in acute pancreatitis.