[Parameters of connective tissue metabolism as markers in acute and chronic pancreatitis. A retrospective study with a cohort of normal subjects]. / Parameter des Bindegewebsstoffwechsels als Marker bei akuter und chronischer Pankreatitis. Eine retrospektive Studie mit Erhebung eines Normalkollektivs.

It is suggested that during active phases of acute and chronic pancreatitis (aP and cP) a major breakdown of extracellular matrix occurs. Since our group previously established that serum levels of the precollagen-III-peptide (P-III-P) are good markers for changes in the extracellular matrix in liver disease (e.g. fibrosis and cirrhosis), we investigated whether this would also serve as a possible marker for pancreatitis. A total of 52 patients with pancreatitis were studied (aP = 17; cP = 35) and compared to 194 controls. Diagnosis of pancreatitis was done on the basis of established classifications. Concomitant diseases, e.g. of the liver, were excluded. Serum levels of P-III-P (three assays with polyclonal and monoclonal antibodies and Fab-Fragments), hyaluronic acid (HA) and laminin (LAM) were measured by RIA or IRMA. Patients with pancreatitis displayed elevated levels in all groups, when compared with the controls. Since the P-III-P-Fab RIA measures the Col1-fragment by 50%, which is considered to be a degradation product of P-III-P, this could mean that neogenesis of collagen is paralleled by degradation during the initial course of an acute episode of pancreatitis. The ratio (quotient) of P-III-P-Fab and P-III-PMoAb (nl = 127.3 +/- 27) is changed in patients with pancreatitis towards P-III-P-Fab (aP: 115.4 +/- 84.7*, cP: 94.9 +/- 21.8*, cP-I: 89.3 +/- 9.2*; * = p = 0.0001).(ABSTRACT TRUNCATED AT 250 WORDS)

Comparison of CA 72-4 with CA 19-9 and carcinoembryonic antigen in the serodiagnostics of gastrointestinal malignancies.

Serum levels of the new tumor-associated marker CA 72-4 were measured in healthy controls (n = 64) and patients with benign (n = 410) or malignant (n = 199) gastrointestinal diseases. A cut-off limit of 4 U/ml was established. Tumor-indicating sensitivity was compared with that of the conventional markers carcinoembryonic antigen (CEA) and CA 19-9. In serodiagnostic evaluations CA 72-4 was clearly inferior to CA 19-9 in pancreatic carcinomas (22% versus 82%; all stages) and to CEA in colorectal cancer (32% versus 58%; all stages), with no appreciable diagnostic gain from combined determination. However, in gastric carcinoma CA 72-4 identified 59% of all patients (CA 19-9, 52%; CEA, 25%), and a combination of CA 72-4 and CA 19-9 detected as many as 70%. Positive results correlated roughly with tumor size. Compared with the other two tumor markers, CA 72-4 had a very high specificity (98%) in benign diseases of the gastrointestinal tract, including inflammatory processes, so that elevated serum levels of CA 72-4 should always be taken seriously.

Exocrine pancreatic function after gastrectomy. Specificity of indirect tests.

We compared intraindividually the specificity of indirect pancreatic function tests before and after total (n = 4; Roux-en-Y) or subtotal (n = 6; Billroth II) gastrectomy. Before gastrectomy only 1 patient showed a falsely pathological result with the pancreolauryl test (90% specificity), while the results of all the other tests were correctly normal (100% specificity using the usual cutoff limits). After gastrectomy the respective specificities were as follows: pancreolauryl test 10%, bentiromide test 70%, fecal chymotrypsin 70%, and plasma amino acid consumption test 100%. There was no obvious difference in the reduction of specificity between subtotal and total gastrectomy. The respective preoperative to postoperative changes in the median test data were as follows: plasma amino acid consumption test +21%, bentiromide test -12%, fecal chymotrypsin -51%, and pancreolauryl test -53%. It is concluded that after gastrectomy only the plasma amino acid consumption test is unaffected by postoperative anatomic alterations.

[Amino acid level in plasma--expressed as alpha-amino-nitrogen--reaction to stimulation of the exocrine pancreas: approaches to a new pancreatic function test]. / Aminosäurespiegel im Plasma--dargestellt als alpha-Amino-Stickstoff--reagieren auf Stimulation des exokrinen Pankreas: Ansätze für einen Pankreasfunktionstest.

We determined by the ninhydrin method the plasma amino acid (AA) levels prior to, during and following, a 1-hour i.v. infusion of 1 U/kg body weight each of secretin and pancreozymin in patients with normal (n = 74) or reduced (n = 39) exocrine pancreatic function, as assessed by the duodenal aspiration test. The results of the two tests correlated significantly with each other (p less than 0.001). A maximum AA decrease of greater than or equal to 12% was observed in all patients with a normally functioning pancreas (specificity 100%), and of less than 12% in all patients with medium to high-grade impairment of pancreatic function (sensitivity 100%). Since, however, low-grade pancreas insufficiency (20-40% of the mean normal enzyme output) is recognized in fewer than one-half of the cases, the overall sensitivity of the AA-consumption test decreases to 69%. The results can, however, be improved by: 1) Calculating the mean percentage AA decrease with a limit value of 5% (sensitivity 90%); 2) determining individual AA with pancreas-specific absorption, such as serine (sensitivity 92%); 3) dropping the lower normal value of exocrine pancreatic function to 25% of the normal mean enzyme output (sensitivity 96%). Diseases that may be associated with the most common condition that causes pancreatic insufficiency--chronic pancreatitis--and which have an influence on AA metabolism, such as cirrhosis of the liver and diabetes mellitus, have no influence on the accuracy of the AA consumption test, which, considered overall, represents a competitive alternative to other tubeless tests of pancreatic function.

NMR spectrometry. A new method for total stool fat quantification in chronic pancreatitis.

In the present investigation, suitability of nuclear magnetic resonance (NMR) spectrometry for total stool fat quantification in patients with normal or impaired exocrine pancreatic function (chronic pancreatitis) has been analyzed in comparison with a conventional chloroform-methanol extraction technique. Basic temperature-dependence studies of NMR spectrometry (90 degrees/180 degrees radiofrequency pulse sequence) on 21 chloroform-methanol extracted pure total stool lipid standards (weight range: 0.05-1.6 g) revealed significantly (P less than 0.05) improving correlations between NMR signal amplitudes and corresponding weights at increasing temperatures (r = 0.952/40 degrees C, r = 0.965/60 degrees C, r = 0.988/80 degrees C), thus indicating 80 degrees C as optimal temperature for NMR spectrometric total stool fat quantification. In subsequent comparative measurements of lyophilized stool samples, NMR spectrometry (at 80 degrees C) and conventional chloroform-methanol extraction provided significantly (P less than 0.001) correlated results with respect to total fecal fat contents/day of quantitatively collected and homogenized stools in 93 patients with known exocrine pancreatic function (secretin-pancreozymin test), irrespective of whether correlations were determined for all 93 patients (r = 0.983) or separately for patients with normal (N = 45; r = 0.867), moderately reduced (N = 31; r = 0.946), or highly reduced (N = 17; r = 0.992) exocrine pancreatic function and correspondingly increased total fecal fat excretions.

Whipple's procedure plus intraoperative pancreatic duct occlusion for severe chronic pancreatitis: clinical, exocrine, and endocrine consequences during a 3-year follow-up.

The present investigation provides follow-up data (up to 36 months) of exocrine and endocrine pancreatic function, inflammatory activity, pain, and body weight in 23 chronic pancreatitis patients submitted to Whipple's procedure plus intraoperative Ethibloc occlusion of the remaining pancreatic duct system between January 1983 and February 1984. Clinically, Whipple's procedure plus intraoperative pancreatic duct occlusion resulted in almost complete and continuous cessation of pain as well as significant (p less than 0.05) increase in body weight. With regard to exocrine pancreatic function (Secretin-Pancreozymin test, plasma amino acid consumption test, Pankreolauryl test, fecal chymotrypsin determination), intraoperative pancreatic duct occlusion was shown to induce high-grade insufficiency and thus exocrine parenchymal atrophy in all patients. Simultaneously, the inflammatory process (represented by serum levels of trypsin, lipase, and pancreatic isoamylase) was terminated in all 23 patients. Endocrine pancreatic function, evaluated by serum levels of insulin and C-peptide measured under fasting conditions and subsequent maximal combined beta-cell stimulation as well as corresponding integrated hormone releases, was reduced by partial pancreas resection by about 50%, while there was no further impairment during the 36-month follow-up period in consequence of additional intraoperative pancreatic duct occlusion. Altogether, Whipple's procedure plus intraoperative Ethibloc occlusion of the residual pancreatic duct system seems suitable for termination of the inflammatory process and thus preservation of residual endocrine pancreatic function in chronic pancreatitis.

Decrease in plasma amino acid level after secretin and pancreozymin as an indicator of exocrine pancreatic function.

Total plasma amino acids were determined by the ninhydrin method in 37 controls and 30 patients with chronic pancreatitis and normal (n = 7) pancreatic enzyme output or mildly (n = 6), moderately (n = 8), and severely (n = 9) reduced pancreatic enzyme output. Intravenous injection of synthetic secretin did not change plasma amino acid levels. During a combined intravenous infusion of secretin (1 CU/kg X h) and pancreozymin (1 Ivy dog unit/kg X h), amino acid concentrations decreased maximally by 31% +/- 19% (mean +/- SD) in controls, but only by 6.3% +/- 4.7% in patients with exocrine pancreatic insufficiency (p less than 0.001 vs. controls). At a cutoff limit of less than or equal to 12% for the decrease in total amino acids, mild exocrine insufficiency (20%-40% of mean normal chymotrypsin output) was identified with a sensitivity of 67%, whereas moderately to severely impaired function was detected in every case (overall sensitivity 91%). Pancreatic function, as assessed by duodenal intubation and the tubeless amino acid test, was significantly correlated (e.g., rs = 0.73 for chymotrypsin output, p much less than 0.001). In 15 controls and 13 patients with mildly (n = 5) to severely impaired pancreatic function, individual amino acids were estimated. Plasma serine kinetics completely distinguished both groups. Kinetics of serine, valine, isoleucine, and histidine correlated even better with pancreatic function than those of total amino acids.

[Comparison of CA 50 and CA 19-9 tumor markers in benign and malignant diseases of the upper gastrointestinal tract]. / Vergleich der Tumormarker CA 50 und CA 19-9 bei benignen und malignen Erkrankungen des oberen Gastrointestinaltraktes.

Tumour-associated antigens CA 50 and CA 19-9 were determined in serum of 208 patients. Specificity of both neo-antigens as tumour markers was equally good, at 100% and 95%, in patients without malignancy or gastrointestinal disease, respectively, using an upper limit of normal of 17 U/ml for CA 50 and 37 U/ml for CA 19-9. Benign diseases of the upper gastrointestinal tract, such as pancreatitis, cholestasis or cirrhosis of the liver, reduce the specificity of CA 50 more than of CA 19-9. For example, specificity of CA 50 is only 33% for choledocholithiasis, but 74% with CA 19-9. The sensitivity of both closely related sialogangliosides in malignancies of the upper GI tract is similar, with the usual normal limits: in pancreas carcinoma 77% for CA 50, 81% for CA 19-9; in biliary tract carcinoma 80% for CA 50, 90% for CA 19-9; in gastric carcinoma 40% for CA 50, 50% for CA 19-9. But if one equalizes the upper limits of normal for both markers to a common 95% specificity, the tumour-indicating sensitivity of CA 19-9 clearly surpasses that of CA 50. Malignant tumours not recognized by increased levels of CA 19-9 also escape serological diagnosis with CA 50.

NMR spectrometric stool fat analysis--a new technique for quantifying steatorrhea and establishing the indication for enzyme replacement in chronic pancreatitis.

In 93 patients with known exocrine pancreatic function (secretin-pancreozymin test), NMR spectrometry and chloroform-methanol extraction of quantitatively collected, homogenized and lyophilized stools provided significantly correlated results with respect to stool fat concentration (r = 0.872) and total stool fat excretion/day (r = 0.983). In 83% of 24 patients with total stool fat excretion/day of more than 15 g (chloroform-methanol extraction), the indication for enzyme replacement was also established by stool fat concentrations of more than 35% determined by NMR spectrometry, irrespective of whether stool fat was measured in total stools or in 3 consecutive unhomogenized samples. In the remaining (17%) patients total stool fat excretion/day was only slightly elevated (16-21 g). Interestingly, in only 58% of patients actually needing enzyme replacement, did the secretin-pancreozymin test reveal a reduction of stimulated enzyme secretion to below 15% of the lower normal limit. The results indicate that NMR spectrometry of lyophilized samples of 3 consecutive unhomogenized stools is suitable for stool fat quantitation and for establishing the indication for enzyme replacement in chronic pancreatitis.

[Importance of the tumor-associated antigen CA 19-9 in the differential diagnosis of pancreatic diseases]. / Bedeutung des tumorassoziierten Antigens CA 19-9 in der Differentialdiagnose von Pankreaserkrankungen.

Tumour-associated antigen CA 19-9 was determined in serum from 166 patients (30 without gastro-intestinal disease, 32 with liver cirrhosis, 9 with choledocholithiasis, 65 with acute or chronic pancreatitis and 30 with malignant tumors in the region of pancreas and bile passages). The specificity of CA-19-9 as tumour marker was 97% in patients without gastro-intestinal disease, but in those with liver cirrhosis or choledocholithiasis it was only 56% and 44%, respectively. In particular, cholestasis reduced specificity. Acute pancreatitis in its initial attack gave false-positive CA 19-9 values in 27% of cases, repeated bouts in chronic recurrent pancreatitis in as many as 50%. In chronic pancreatitis the specificity was 90%. Malignant tumours of pancreas and bile ducts were diagnosed with a sensitivity of 80%. Determination of CA 19-9 in pure pancreatic secretion failed to differentiate between the control group (30), chronic pancreatitis (21) and carcinoma of the pancreas (22).

Pancreatic enzyme replacement therapy: comparative effects of conventional and enteric-coated microspheric pancreatin and acid-stable fungal enzyme preparations on steatorrhoea in chronic pancreatitis.

The therapeutic effectiveness of a conventional (Pankreon-Granulat) and an acid-protected (Kreon) porcine pancreatic enzyme preparation, and an acid-stable fungal enzyme preparation (Nortase) in the treatment of severe pancreatogenic steatorrhoea was investigated. The study comprised 17 patients with chronic pancreatitis and exocrine pancreatic insufficiency with (A) or without (B) a previous Whipple's procedure (B II resection + partial duodenopancreatectomy). With all three enzyme preparations, a significant (p less than 0.05) reduction in the total faecal fat excretion/day was achieved. In therapy group A, this reduction was, on average, 58% for Kreon (100,000 U lipase/day), 67% for Pankreon-Granulat (360,000 U lipase/day) and 54% for Nortase (75,000 U lipase/day), the respective figures for therapy group B being 58%, 52% and 46% at identical dosages. Thus, in both groups, the effect produced by the conventional porcine pancreatic enzyme preparation and the acid-protected porcine or the acid-stable fungal enzyme preparation was largely equivalent, although the latter two preparations were administered at only 1/4 of the dosages of the former preparation. On the basis of the respective average reduction in total faecal fat excretion and average number of stools/day, it would appear that in patients with chronic pancreatitis and prior Whipple's procedure, Pankreon-Granulat should be administered for enzyme replacement while in patients with an intact upper gastrointestinal tract, Kreon should be administered, in the treatment of steatorrhoea in chronic pancreatitis.

[Therapeutic pancreatic duct occlusion in chronic pancreatitis: clinical, exocrine and endocrine consequences in a 12 month follow-up study]. / Therapeutische Pankreasgangocclusion bei chronischer Pankreatitis: klinische, exokrine und endokrine Konsequenzen bei 12monatiger Nachbeobachtung.

Therapeutic pancreatic duct occlusion (PDO) is applied to preserve endocrine pancreatic function by atrophizing and thus eliminating chronically inflamed exocrine pancreatic parenchyma. So far, efficient and lasting elimination of exocrine parenchyma is brought about only by intraoperative PDO upon partial duodenopancreatectomy. While partial duodenopancreatectomy itself reduces endocrine pancreatic function by about 40%, intraoperative PDO does not further impair endocrine function. Endocrine function is not affected at all by endoscopic PDO, which has to be improved, however, concerning its eliminatory effect on exocrine pancreatic parenchyma.

[Comparison of the tumor markers CEA and CA 19-9 in colorectal diagnosis]. / Vergleich der Tumormarker CEA und CA 19-9 in der kolorektalen Diagnostik.

Endoscopic examination of the colon was performed in 405 patients (125 without, 217 with benign, and 63 with malignant colorectal diseases), and the serum levels of the tumour-associated antigens CEA and CA 19-9 were determined. On comparing both markers, the specificity of CA 19-9 (96% correctly normal values) was found to be higher in benign colorectal diseases than that of CEA (92% with a cut-off limit of 5 ng/ml for CEA). On the other hand, the sensitivity of CA 19-9 in colorectal carcinomas was only about 25% and thus much lower than that of CEA (52% correctly pathological values). The sensitivity of both markers was particularly low in the initial stages of carcinoma (in Dukes A: CEA 20%, CA 19-9 0%). If the cut-off limit for CEA was raised to 10 ng/ml, the specificity was increased to 99%, whereas the sensitivity was markedly reduced to 25%. The diagnostic accuracy of CEA in colorectal carcinomas was not surpassed by CA 19-9. There was no obvious advantage in simultaneous determination of CEA and CA 19-9.

[Effect of plant fibers on the lipolytic and proteolytic function of the exocrine pancreas]. / Einfluss von Pflanzenfasern auf die lipolytische und proteolytische exokrine Pankreasfunktion.

Ingestion of the plant fiber guar in therapeutic dosage (20 g/d) in 20 healthy probands led to a highly significant (P less than 0.01) inhibition of lipolytic and a clearly less effective (0.05 greater than P greater than or equal to 0.01) inhibition of proteolytic exocrine pancreatic function. Plant fibers with a highly significant in-vivo inhibition of lipolytic exocrine pancreatic function such as guar gum should thus not be administered to patients with exocrine pancreatic insufficiency and steatorrhoea. However, they should be considered as additional measures in drug treatment of hypertriglyceridaemia.