Serum Trypsin Levels Research Articles

Trypsin may be associated with duodenal eosinophils through the expression of PAR2 in early chronic pancreatitis and functional dyspepsia with pancreatic enzyme abnormalities.

Early chronic pancreatitis (ECP) has been reported to advance into chronic pancreatitis, it may be critical to differentiate the pathophysiology of ECP and functional dyspepsia (FD) in patients with pancreatic enzyme abnormalities (FD-P). This study aimed to clarify differences in the pathophysiology of ECP and FD-P and to determine whether duodenal inflammatory responses in the two diseases were associated with protease-activated receptor (PAR) 2, as the trypsin receptor. Eighty patients who presented with FD-P and ECP were enrolled. In duodenal specimens, PAR2 mRNA levels were determined using real-time PCR. Using immunostaining, CD68-, GLP-1-, PRG2-, and CCR2-positive cells, tight junction proteins, and PAR 2 were evaluated. There were no significant differences in clinical symptoms and gastric motility between ECP and FD-P patients. The CD68-positive cells infiltrations and occludin expression levels in the duodenal mucosa of patients with FD-P were significantly (p<0.001 and p = 0.048, respectively) lower than those in patients with ECP. Although serum trypsin levels in ECP and FD-P patents were significantly (p<0.05 and p<0.001, respectively) associated with duodenal eosinophils counts, elevated trypsin levels were not significantly associated with degranulated eosinophils, occludin, claudin-1 and ZO-1 expression levels in the duodenum of either group. PAR2 mRNA levels were increased in the duodenum of patients with ECP and FD-P. PAR2 was localized in the epithelial cells of the duodenal mucosa and the surface of degranulated eosinophils in ECP and FD-P patients. Elevated trypsin levels might be partly associated with duodenal inflammatory responses through PAR2-related degranulated eosinophils and the reduction of occludin in patients with ECP and FD-P.

Low Serum Trypsin Levels Predict Deep Pancreatic Cannulation Failure During Endoscopic Retrograde Cholangiopancreatography in Patients With Symptomatic Obstructive Chronic Pancreatitis

Deep pancreatic cannulation (DPC) failure during endoscopic retrograde cholangiopancreatography (ERCP) in patients with chronic pancreatitis (CP) can occur in the presence of ductal obstruction due to strictures and/or stones. There are currently no simple preprocedure clinical or laboratory tests that can predict DPC failure during ERCP. All adult patients with definite CP by M-ANNHEIM criteria referred to the pancreatitis clinic between 2010 and 2017 were evaluated. Serum trypsin levels were obtained to assess the morphologic severity of disease and/or exocrine insufficiency. Univariable and multivariable logistic regression analyses were performed to identify factors associated with DPC failure. There were 346 patients, of whom 100 underwent trypsin measurements and ERCP for symptomatic CP. Deep pancreatic cannulation failure occurred in 32 (32%). There were no significant differences with regard to age, sex, etiology, smoking, and alcohol use. Deep pancreatic cannulation failure was more likely to occur in patients with low trypsin levels (53.1% vs 25%, P = 0.007) compared with those with successful DPC. Low trypsin levels were independently associated with DPC failure in adjusted analysis (odds ratio, 3.7; 95% confidence interval, 1.2-11; P = 0.02). Low serum trypsin levels independently predict DPC failure during ERCP in patients with symptomatic obstructive CP.

Low serum trypsin levels predict deep pancreatic cannulation failure during ERCP in patients with symptomatic obstructive chronic pancreatitis

Advances in cell and molecular biology studies have revolutionized the diagnosis and treatment of many different diseases. Cell and molecular diagnostics (CMD) have become an essential part of investigations required in providing optimal care and has become an important tool for the health care providers for better treatment. CMD gives insights into the pathogenesis and prognosis of various diseases. Rapid technological advances have helped to increase the speed and performance of various molecular assays thereby reducing turnaround time, in turn translating to providing better clinical services. With the increase in CMD applications to clinical services, entire world has seen a sudden spurt of cellular and molecular labs. However, this has highlighted an acute shortage of trained laboratory personnel who can carry out cellular or molecular assays in a diagnostic mode. Understanding the mechanisms of disease at the molecular and genetic levels can now be translated into diagnostic, prognostic, and therapeutic applications in modern medicine. Molecules at abnormal levels (quantitative or qualitative) provide not only a signature for the presence of a disease, but also the indication for a drug targeting the specific abnormal function. Concurrently, the role of CMD has expanded from mere study observations to constantly translating new discoveries and novel technologies into useful clinical tests that provide a molecular fingerprint of diseases and that are predictive of the response. In the introductory chapter we will cover the importance of biological sample collection from different methods; cell-based diagnostic methods, cellular pathway diagnostic targets, and molecular-based methods.

The Relationship between Trypsin/Calcitonin Gene Related Peptide (CGRP) in Serum and Acute Pancreatitis (AP).

Activation of trypsin from proteolytic cleavage of trypsinogen in the pancreas can lead to acute pancreatitis. Calcitonin gene related peptide (CGRP) from both peripheral and central neurons is involved in a variety of physiological/pathophysiological processes, especially sensory (nociceptive) and efferent (effector) functions. To better understand the change of trypsin/CGRP in acute pancreatitis, the study investigated the serum level of trypsin/CGRP in patients with acute pancreatitis. The study investigated 140 patients with acute pancreatitis, including 72 cases of biliary acute pancreatitis, 60 cases of hyperlipidemic acute pancreatitis, and 8 cases of idiopathic acute pancreatitis. Sixty volunteers acted as the normal control group. The levels of trypsin and CGRP in serum were analyzed. The serum levels of trypsin and CGRP in males with acute pancreatitis were higher than in females, but there was no statistical difference (p > 0.05). However, the serum levels of trypsin and CGRP in different types of acute pancreatitis were significantly higher than controls (p < 0.001), and the level of trypsin and CGRP in serum of patients with inflammation effusion was significantly higher than patients without inflammation effusion (p < 0.001). In addition, the serum levels of trypsin and CGRP in patients with I-II, III, IVA and IVB acute pancreatitis were higher than controls (p < 0.001). According to the results, we concluded that the trypsin and CGRP in serum can act as a new detection index of acute pancreatitis occurring. The serum levels of trypsin and CGRP in patients with acute pancreatitis is able to determine whether inflammation effusion happens.

BLOOD SERUM TRYPSIN LEVELS IN CHILDREN WITH ACUTE VIRAL HEPATITIS AND THEIR ASSOCIATIONS WITH THE CLINICAL AND LABORATORY MANIFESTATIONS OF THE DISEASE

The objective of the study was to determine blood serum trypsin levels in children with mild viral hepatitis B and their correlations with the clinical and laboratory manifestations of the disease. Studied were 48 children aged 3 to 15 years. The first group comprised 33 patients with mild hepatitis B. The second (control) group comprised 15 healthy children. All hepatitis patients had significantly increased blood trypsin levels suggesting that their disease was combined hepatopancreatitis. Blood trypsin levels were found to correlate with the clinical and laboratory manifestations of the disease and its enzymatic exaggerations associated with delayed recovery. Blood serum trypsin levels were found to correlate linearly with the specific markers of hepatitis: HBs antigen level at patient’s admission and the duration of increases in HBs and HBe levels. This suggests that serum trypsin may be the earliest prognostic marker of lingering and chronic disease. It is recommended to treat the icteric forms of hepatitis B in children as combined conditions (hepatopancreatitis) and to follow-up and cure such patients in collaboration of infectiologists with gastroenterologists in order to reduce the incidence of complication and adverse outcomes and to timely recognize lingering and chronic pancreatitis in children.

Application of an Electrochemical Immunosensor with a MWCNT/PDAA Modified Electrode for Detection of Serum Trypsin

Objective: To establish an electrochemical immunosensor for the determination of serum trypsin levels using a multiwall carbon nanotubes (MWCNTs)-composite-modified electrode. Method: A MWCNT composite coated on the surface of bare gold electrodes was used for fixation of an anti-trypsin antibody. The assembly process and the performance indicators, including sensitivity, linear range of detection, anti-jamming performance, and stability, of the electrochemical immunosensor were examined by cyclic voltammetry (CV) and electrochemical impedance spectroscopy (EIS). Results: With optimized experimental conditions, the difference of the current value measured by differential pulse voltammetry (DPV) showed a linear relationship with the concentration of serum trypsin within 0.10–100 ng/mL. The detection limit for trypsin using this sensor was 0.002 ng/mL. Conclusions: The electrochemical immunosensor built using the MWCNT-composite-modified electrode is simple to operate and has a fast response time, along with a wide linear range, high sensitivity, and accuracy, making it suitable for serum trypsin detection.

High serum trypsin levels and the -409 T/T genotype of PRSS1 gene are susceptible to neonatal sepsis.

Neonatal sepsis remains an important and common cause of morbidity and mortality among newborn infants, especially in developing countries. The aim of the present study was to determine whether serum trypsin levels and genotypes of cationic trypsinogen (PRSS1) gene could be served as markers for predicting neonatal sepsis. The serum trypsin levels and genotypes of PRSS1 were examined in both 50 infants with infection during neonatal period and 56 healthy neonates as controls. The infected infants were further subdivided into infants with sepsis group (n=18) and infected infants without sepsis (n=32). The genotype of PRSS1 was analyzed by direct sequencing, and the serum trypsin level was measured by immunoassay. It showed that the median value of serum trypsin was significantly higher in infected infants (31.90 ng/mL) than in controls (12.85 ng/mL; P=0.030). More importantly, sepsis subgroup (50.95 ng/mL) had significantly higher median serum trypsin than infected infants without sepsis subgroup (19.10 ng/mL) and controls (12.85 ng/mL) (P=0.015 and P=0.002, respectively). Additionally, the median serum trypsin levels were found significantly higher in infants who had T/T (37.90 ng/mL) genotype of PRSS1 compared with those who had C/T genotype (12.80 ng/mL; P=0.005). This study suggested that serum trypsin and rs10273639 C/T of PRSS1 were revealed to be novel markers for predicting neonatal sepsis.

Serine proteases affect in situ vasa recta capillary diameter: mechanism for kidney failure associated with pancreatitis?

Serine proteases are proteolytic enzymes involved in the regulation of renal function and hemodynamics. Serum trypsin (the archetypal serine protease) levels are elevated in a number of pathophysiological conditions, notably pancreatitis, which is associated with acute renal failure.Here we use the kidney slice model to investigate the effect of trypsin on vasa recta diameter in situ. Kidney slices (200 μm thick) were obtained from adult male rats as previously described [1]. Kidney slices were superfused with trypsin and DIC video imaging techniques were used to record real‐time changes in vasa recta diameter.Application of trypsin (2 U/ml) caused a significant constriction of vasa recta capillaries, specifically at smooth muscle‐like pericyte cell sites (15.5±1.4% p&lt;0.05).Here we demonstrate that acute application of trypsin (at levels similar to those detected in patients with severe acute pancreatitis) significantly decreases vasa recta diameter and thus renal medullary blood flow, specifically via its action at pericytes. Data presented here identifies a novel potential role for pericytes in the acute renal failure observed in patients with acute pancreatitis.Research supported by BBSRC, Wellcome Trust and the MRC

PRSS1 intron mutations in patients with pancreatic cancer and chronic pancreatitis

Genetic risk factors of chronic pancreatitis (CP) have been identified and a number of studies have found that CP can lead to pancreatic cancer. Therefore, the detection of pancreatitis-associated gene mutations can aid the pancreatic cancer diagnostic process. Mutations in three genes, the cationic trypsinogen (PRSS1) gene, the cystic fibrosis transmembrane conductance regulator (CFTR) gene and the pancreatic secretory trypsin inhibitor (SPINK1) gene, have been identified as risk factors for CP. The aim of this study was to describe specific novel mutations in the intron of the PRSS1 gene in patients with pancreatic cancer and CP. A total of 65 unrelated patients with pancreatic cancer and 29 with CP were reviewed. Mutations and polymorphisms of the PRSS1 gene were analyzed by direct sequencing. Information regarding clinical data and smoking exposure was collected by personal interviews using a structured questionnaire. IVS 3+36 A>G mutation in the PRSS1 gene was found in 2 cases with pancreatic cancer, and these 2 patients were classified as never-smokers. IVS 3+127 T>A and IVS 3+157 G>C double mutations were identified in one patient with CP. All patients were found to have serum trypsin levels lower than that of the normal controls. Therefore, the PRSS1 gene mutation may be a special common cause of pancreatic cancer and CP.

The −409 C/T Genotype of PRSS1 Protects Against Pancreatic Cancer in the Han Chinese Population

The high mortality rate of pancreatic cancer is a bottleneck for further treatment with long-term efficacy. Thus, it is urgent to identify new methods to accurately predict the early onset of pancreatic cancer. We hypothesized that the different genotypes of cationic trypsinogen (PRSS1) gene could confer susceptibility and/or resistance to pancreatic cancer in the Han Chinese population. The genotypes of PRSS1 were determined in 154 patients with pancreatic cancer and in a control group of 520 healthy individuals of Han Chinese descent. Clinical information was obtained, single-nucleotide polymorphisms (SNPs) of the PRSS1 gene were analyzed by direct sequencing, and the distribution of the genotypes were tested for Hardy-Weinberg equilibrium. Odds ratios and 95% confidence intervals were calculated by logistic regression analysis to estimate the associations between the different genotypes or haplotypes and the risk of pancreatic cancer. Three SNPs (-409 C/T, -204 A/C, and c.486 C/T) were identified. A case-control analysis revealed a 0.118-fold (95% CI: 0.037-0.653), 0.842-fold (95% CI: 0.177-4.010), and 0.750-fold (95% CI: 0.519-1.085) change in risk of developing pancreatic cancer for individuals harboring these SNPs, respectively. The individuals with the -409 C/T genotype tended to have a reduced risk compared to those who carried the -409 T/T genotype. A protective effect was observed for the C(-409)-A(-204)-C(486) haplotype compared to the T(-409)-A(-204)-T(486) haplotype (OR = 0.115, 95% CI: 0.016-0.849) or compared to the T(-409)-A(-204)-C(486) haplotype (OR = 0.090, 95% CI: 0.012-0.667). Serum levels of trypsin in patients with the -409 C/T genotype were only one-fourth that of those with the -409 T/T genotype and only one-third that of the healthy controls. The -409 C/T genotype of PRSS1 was revealed to be a protective factor against pancreatic cancer in the Han Chinese population.

A Case of Shwachman-Diamond Syndrome Confirmed with Genetic Analysis in a Korean Child

Shwachman-Diamond syndrome (SDS) is an autosomal recessive genetic disorder, consisting of exocrine pancreatic insufficiency, chronic neutropenia, neutrophil chemotaxis defects, metaphyseal dysostosis, short stature, dental caries, and multiple organ involvements. Although SDS is the second most common hereditary abnormality of exocrine pancreas following cystic fibrosis in the Western countries, it has rarely been reported in Asia. We diagnosed a case of SDS in a 42-month-old girl, and genetic analysis including the relatives of the patient confirmed the diagnosis for the first time in Korea. She had short stature, steatorrhea, dental caries, and recurrent prulent otitis media and pneumonias. Laboratory studies revealed cyclic neutropenia, and serum levels of trypsin, amylase, and lipase were decreased. Simple radiography revealed metaphyseal sclerotic changes at the distal femur. A CT scan demonstrated a fatty infiltration and atrophy of the pancreas. On direct sequencing analysis of Shwachman-Bodian-Diamond Syndrome gene exon 2 region, the patient was homozygous for the c.258+2T>C mutation and heterozygous for the c.183_184TA>CT mutation and c.201A>G single nucleotide polymorphism. Treatment with pancreatic enzyme replacement, multivitamin supplementation, and regular to high fat diet improved her weight gain and steatorrhea.

Prospective study of pancreatic b-cell and exocrine function following duct decompression in tropical calcific pancreatitis.

Tropical calcific pancreatitis (TCP) is a chronic, nonalcoholic pancreatitis, which is limited to developing countries. In this condition, surgical decompression of the pancreatic duct consistently leads to relief of abdominal pain. However, no data are available on the effect of such intervention on pancreatic function. The aim of the present study was to prospectively evaluate b-cell and exocrine function following ductal drainage in patients with TCP. We studied 14 consecutive TCP patients who underwent ductal decompression for abdominal pain (longitudinal pancreaticojejunostomyin 12 patients, endoscopic sphincterotomy and ductal stenting in 2 subjects). Six patients who refused similar intervention served as controls. Patients were evaluated prospectively (median follow-up 13 months) for pain score, fasting and oral glucose stimulated plasma C-peptide, serum trypsin, and fecal chymotrypsin. After intervention, 1 patient died 2 months after surgery, and 2 others were lost in follow-up. The pain score improved significantly following duct decompression (median 8.0 vs. 0, p < 0.01), while in the control group there was no change in pain score (7.0 vs. 7.0). There was no change in b-cell function after intervention (fasting plasma C-peptide [mean +/- SEM] 0.41 +/- 0.08 vs. 0.42 +/- 0.05 nmol/l; peak plasma C-peptide 2.24 +/- 0.20 vs. 2.32 +/- 0.24 nmol/l). Fecal chymotrypsin was diminished in all patients prior to intervention (1.9 +/- 0.7 U/g), and did not normalize after ductal drainage in any subject. Serum trypsin levels were variable, being elevated in 29% and diminished in 47% of subjects. All 4 subjects with elevated baseline trypsin levels had a sharp fall after intervention (1020 vs. 175 ng/ml). However, serum trypsin did not normalize after ductal drainage in any patient with a diminished baseline value. In conclusion, patients with TCP have significant reduction in abdominal pain after decompression of the main pancreatic duct. However, there is no significant change in b-cell function. A fall in elevated serum trypsin suggests that there may be relief of subclinical inflammation after intervention; however, there is no improvement in exocrine function after a follow-up of 1 year.

MR imaging of pancreatic changes in patients with transfusion-dependent beta-thalassemia major.

The aim of this study was to evaluate MR imaging changes of the pancreas in patients with transfusion-dependent beta-thalassemia major. Twenty patients with transfusion-dependent beta-thalassemia major were examined using MR imaging at 0.5 T, with spin-echo T1-weighted, fast spin-echo T2-weighted, and gradient-echo T2*-weighted sequences. Image analysis was performed to assess pancreas-to-fat signal intensity ratios for all pulse sequences. Pancreatic exocrine and endocrine function and serum ferritin levels were assessed. Twenty healthy volunteers underwent MR imaging with the same three sequences and served as a control group. The pancreas-to-fat signal intensity ratio was significantly decreased in 17 (85%) of the 20 patients on spin-echo T1-weighted images (p < .05), fast spin-echo T2-weighted images (p < .01), and gradient-echo T2*-weighted images (p < .01) when compared with the 20 volunteers in the control group. The pancreas-to-fat signal intensity ratio was significantly increased in three (15%) of the 20 patients on spin-echo T1-weighted images (p < .01) and fast spin-echo T2-weighted images (p < .05). In addition, in the 20 patients, we found a significant correlation between increased pancreas-to-fat signal intensity ratios and decreased serum trypsin levels (r = -.77, p < .01 for spin-echo T1-weighted sequences; r = -.75, p < .05 for fast spin-echo T2-weighted sequences; and r = -.74, p < .05 for gradient-echo T2*-weighted sequences). Likewise, for the 20 patients, we found a significant correlation between decreased pancreas-to-fat signal intensity ratios and increased serum ferritin levels for gradient-echo T2*-weighted images (r = -.65, p < .01). No correlation was found for the other clinical parameters evaluated. MR imaging revealed signal intensity changes in the pancreas of patients with transfusion-dependent beta-thalassemia major. Patients with a major impairment of the exocrine pancreatic function had higher signal intensity of the pancreas because of fatty replacement of the parenchyma.

Increased serum trypsin and elastase-1 levels in patients undergoing L-asparaginase therapy.

Although there is abundant literature on the association of L-asparaginase and acute pancreatitis in patients undergoing chemotherapy, few studies have investigated the usefulness of pancreatic enzyme measurement in the early diagnosis of L-asparaginase-induced acute pancreatitis. We measured levels of serum pancreatic enzymes before, during, and after L-asparaginase therapy in nine children with acute lymphocytic leukaemia or non-Hodgkin lymphoma. Serum levels of amylase, pancreatic isoamylase, and lipase did not change between the 1st and 30th day of L-asparaginase administration. However, the serum trypsin and elastase- levels, 10 and 20 days after beginning L-asparaginase therapy, were significantly higher than those prior to therapy. L-asparaginase may induce subclinical pancreatitis and the estimation of serum trypsin and elastase-1 may be useful in the early diagnosis of L-asparaginase-induced acute pancreatitis.

Prospective evaluation of serum trypsin levels in patients with chronic abdominal pain: [formula omitted] Department of Medicine, Tulane University School of Medicine, New Orleans, LA

Prospective evaluation of serum trypsin levels in patients with chronic abdominal pain: [formula omitted] Department of Medicine, Tulane University School of Medicine, New Orleans, LA

Serum pancreatic enzymes in HIV-seropositive patients

Serum concentrations of trypsin and elastase I were determined in 109 HIV Ab-positive patients (52 asymptomatic HIV-infected patients, 25 with lymphadenopathy syndrome, and 32 with acquired immunodeficiency syndrome) to assess the prevalence of possible pancreatic damage in these patients. Serum trypsin was abnormally elevated in 46 of the 109 patients (42.2%): 19 of the 52 asymptomatic HIV-infected patients (36.6%), 9 of the 25 with lymphadenopathy syndrome (36%), and 18 of the 32 with acquired immunodeficiency syndrome (56.3%). Serum elastase 1 was elevated in 14 of the 109 HIV Ab-positive patients (12.8%): 3 of the 52 asymptomatic HIV-infected patients (5.8%), 3 of the 25 with lymphadenopathy syndrome (12%), and 8 of the 32 with acquired immunodeficiency syndrome (25%). None of the patients with abnormally high serum pancreatic enzyme concentrations had clinically evident pancreatic disease. There was no statistically significant difference in serum levels of trypsin and elastase I between drug addicts and nonaddicts, between alcoholics and nonalcoholics, or between those with cytomegalovirus infection and those without. A significant inverse relationship was found between serum enzyme concentrations and the number of CD4+ lymphocytes. The results of this study show that high levels of serum trypsin and elastase are present in an elevated percentage of patients with acquired immunodeficiency syndrome, suggesting that the pancreas is frequently damaged in this disease. The finding of abnormally high serum enzyme concentrations not only in patients with AIDS, but also in asymptomatic carriers and in patients with lymphadenopathy syndrome suggests an association between HIV infection and the development of pancreatic lesions.

Evaluation of Tests of Exocrine and Endocrine Pancreatic in Function in Older Patients with Cystic Fibrosis

In order to determine the value of noninvasive tests in the analysis of pancreatic function in cystic fibrosis, 14 older cystic fibrosis patients were studied by a set of noninvasive tests of exocrine and endocrine pancreatic function. The tests, comprising trypsin, total amylase, pancreatic isoamylase, lipase, pancreatic polypeptide (PP), glucose and insulin in fasting serum, PP, glucose and insulin in postprandial serum, and p-aminobenzoic acid (PABA) excretion in urine, were compared to fecal fat excretion after discontinuation of pancreatic enzyme supplementation. Eleven of the 14 patients were found to have a fecal fat excretion of more than 7 g/day. Serum levels of trypsin, pancreatic isoamylase and lipase, and the urinary excretion of PABA showed significant negative correlations with fecal fat excretion. Endocrine pancreatic function was abnormal in the majority of patients with fibrocystic disease. Although serum trypsin, postprandial PP, and urinary PABA excretion were the most sensitive tests for severe exocrine pancreatic insufficiency, the differences in sensitivity were rather modest. Therefore, the type of test to be selected for clinical use is mainly dependent upon factors as accessibility, simplicity, patient's acceptability, and costs.

Effects of a Protease Inhibitor, FUT-175, on Pancreatic Enzymes Released after Endoscopic Retrograde Cholangio-Pancreatography

The inhibitory effects of a synthetic protease inhibitor, FUT-175, on the serum levels of pancreatic enzymes, amylase, trypsin, elastase 1, and lipase, in patients subjected to endoscopic retrograde cholangio-pancreatography (ERCP) were examined by the double-blind method. In the untreated group, serum trypsin and lipase levels reached a peak at 2h after the completion of ERCP; and amylase and elastase, at 6h. The serum levels of amylase and lipase recovered to the normal level on the 3rd day, whereas trypsin and elastase did not recover even by the 5th day. By the treatment with FUT-175 at a dose of 10mg or 40mg/day i.v., the increase in serum trypsin level was significantly reduced 2h after ERCP. In chronic pancreatitis patients, the increase in serum amylase level was significantly inhibited 2h after ERCP. FUT-175 also lowered the increased serum levels of other enzymes, but not significantly. These results suggest that FUT-175 is useful to reduce the pancreatic overloading and complications developing after ERCP.

Whippleʼs Procedure Plus Intraoperative Pancreatic Duct Occlusion for Severe Chronic Pancreatitis

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.

Reversibility of exocrine pancreatic failure in chronic pancreatitis

In patients with chronic pancreatitis, the development of exocrine pancreatic failure is generally thought to be an irreversible process. We found evidence to the contrary in a prospective study of 70 patients who were evaluated by endoscopic retrograde cholangiopancreatography and sequential measurements of stool fat, percent urinary PABA excretion, and serum trypsin during a follow-up time period of 1–4 yr. Initial p-aminobenzoic acid (PABA) testing showed exocrine failure in 51 patients, 35 of whom had low serum trypsin levels while 14 (27%) disclosed unexpectedly high trypsin concentrations. Ductal morphology was similar in patients with low and high trypsin values. In 8 of the latter cases, steatorrhea improved and pancreatic function tests became normal after pancreaticojejunostomy in 4 patients, alcohol abstinence in 3 patients, and spontaneous resolution of a pseudocyst in 1 patient. Pancreatic cancer was present in a further 3 patients. Of the 37 patients with low PABA and low trypsin at the outset, there was no improvement of exocrine function in 17 of 18 who were surgically treated. Conservative treatment had a similar effect in another 6 patients who were available for follow-up in this group. The mean duration of symptomatic disease was shorter (p < 0.001) in patients with low PABA and high trypsin levels (1.4 ± 1.2 yr) than in those with low PABA and low trypsin levels (4.5 ± 1.3 yr). The results show that (a) up to 20% of patients with chronic pancreatitis have exocrine pancreatic failure, which is apparently due to early ductal obstruction of a gland with preserved function; (b) this situation can be suspected when low urinary PABA excretion and high serum trypsin levels are simultaneously found; and (c) exocrine failure may be reversible in these patients by using a pancreatic drainage procedure or alcohol abstinence. Such a peculiar pattern of pancreatic function tests may also suggest pancreatic cancer.