alpha-chymotrypsin and Pancreatic-Neoplasms

The aim was to review evidence about diabetes secondary to hereditary pancreatitis, seeking novel diagnostic and treatment features.. Hereditary pancreatitis (HP) is an autosomal dominant condition, characterized by recurrent episodes of acute pancreatitis, progression to fibrosis, and chronic pancreatitis. Clinical presentation includes diabetes of the exocrine pancreas (DEP). HP prevalence ranges from 0.3 to 0.57 per 100,000 people, with up to 80% of these develop DEP. This condition often requires specific interventions: with regard to metabolic control, metformin is the first choice for those with mild DEP, and for those in advanced disease, insulin is considered the first-line therapy. Insulin analogues and insulin pump therapy are preferred due to the brittle glycemic pattern and risk of hypoglycemia. In case of exocrine insufficiency, pancreatic enzyme replacement therapy is recommended. Pancreatic polypeptide administration is a promising novel treatment feature. DEP due to HP appears to be a misdiagnosed condition. The requirement of specific management demonstrates the importance of this matter; therefore, appropriate recognition and classification are important.

Topics: Acute Disease; Carcinoma, Pancreatic Ductal; Chymotrypsin; Diabetes Complications; Diabetes Mellitus; Exocrine Pancreatic Insufficiency; Fibrosis; Humans; Pancreas, Exocrine; Pancreatic Neoplasms; Pancreatitis, Chronic; Recurrence; Risk Factors; Trypsin; Trypsin Inhibitor, Kazal Pancreatic

Individuals with acute recurrent and chronic pancreatitis may have an inherited predisposition to the development of the disease. Pancreatitis in the setting of a significant family history of the disease can be classified as hereditary or familial pancreatitis. In this article, the authors closely examine the specific genes implicated in pancreatitis, investigate the role of genetic testing for diagnosis, and describe the impact of genetic testing results on clinical management.

Topics: Carboxypeptidases A; Chymotrypsin; Claudin-2; Cystic Fibrosis Transmembrane Conductance Regulator; Genetic Predisposition to Disease; Genetic Testing; Germ-Line Mutation; Humans; Pancreatic Neoplasms; Pancreatitis; Receptors, Calcium-Sensing; Risk Assessment; Trypsin; Trypsin Inhibitor, Kazal Pancreatic

Topics: 4-Aminobenzoic Acid; Alkaline Phosphatase; Amylases; Animals; Atrophy; Carnivora; Chymotrypsin; Dog Diseases; Dogs; Exocrine Pancreatic Insufficiency; Feces; Lipase; Pancreas; Pancreatic Diseases; Pancreatic Neoplasms; Pancreatitis; Trypsin

Topics: Amylases; Bicarbonates; Biliary Tract Diseases; Carbohydrate Metabolism; Child; Cholecystokinin; Chymotrypsin; Duodenum; Feces; Humans; Lipase; Methods; Pancreas; Pancreatic Diseases; Pancreatic Hormones; Pancreatic Neoplasms; Pancreatitis; Radiography; Secretin; Trypsin

The chymotrypsin in the stool test was used to monitor adequate enzymatic substitution in treating exocrine pancreatic insufficiency with 18 patients (16 suffering from chronic pancreatitis and 2 having passed duodenopancreatectomy due to pancreatic cancer). This test helps to identify pancreatic insufficiency and can be successfully used in monitoring the adequate amount of pancreatic substitute, which, we have found, differs from patient to patient. The dosage can be higher in cases of chronic pancreatitis than in those required after duodenopancreatectomy.

Topics: Amylases; Chronic Disease; Chymotrypsin; Drug Monitoring; Endopeptidases; Feces; Humans; Lipase; Pancreatic Neoplasms; Pancreaticoduodenectomy; Pancreatin; Pancreatitis

Genome-wide association studies (GWASs) have discovered 20 risk loci in the human genome where germline variants associate with risk of pancreatic ductal adenocarcinoma (PDAC) in populations of European ancestry. Here, we fine-mapped one such locus on chr16q23.1 (rs72802365, p = 2.51 × 10

Topics: Case-Control Studies; Chymotrypsin; Genome-Wide Association Study; Genotype; Humans; Pancreatic Neoplasms; Polymorphism, Single Nucleotide; Quantitative Trait Loci; Sequence Deletion

Although rare, NTRK gene fusions are known to be oncogenic drivers in pancreatic ductal adenocarcinoma (PDAC). We report the response of a metastatic CTRC-NTRK1 gene fusion-positive PDAC to targeted treatment with the oral tropomyosin receptor kinase (TRK) inhibitor larotrectinib and the eventual development of resistance to treatment.. A 61-year-old woman presented with a 2.5-cm mass in the body of the pancreas and a 1.2-cm liver lesion on routine follow-up for endometrial cancer that was in complete remission. Liver biopsy confirmed a primary PDAC unrelated to the endometrial cancer. The patient was treated with gemcitabine, nab-paclitaxel and ADI-PEG 20 for 12 months until disease progression and toxicity emerged [best overall response (BOR): partial response (PR)]. The patient switched to a modified regimen of folinic acid, fluorouracil, irinotecan and oxaliplatin for 4 months until neuropathy occurred. Oxaliplatin was withheld until disease progression 6 months later (BOR: stable disease). Despite recommencing oxaliplatin, the disease continued to progress. At this time, somatic profiling of the liver lesion revealed a CTRC-NTRK1 gene fusion. Treatment with larotrectinib 100 mg twice daily was commenced with BOR of PR at 2 months. The patient progressed after 6 months and was re-biopsied. Treatment was switched to the investigational next-generation TRK inhibitor selitrectinib (BAY 2731954, LOXO-195) 100 mg twice daily. After 2 months, the disease progressed and dabrafenibtrametinib combination therapy was initiated due to existence of a BRAF-V600E mutation. However, the cancer continued to progress and the patient died 2 months later.. Targeted TRK inhibition with larotrectinib in PDAC harbouring a CTRC-NTRK1 gene fusion is well tolerated and can improve quality of life for the patient. However, acquired resistance to therapy can emerge in some patients. Next-generation TRK inhibitors such as selitrectinib are currently in development to overcome this resistance (NCT02576431; NCT03215511).

Topics: Antineoplastic Combined Chemotherapy Protocols; Aza Compounds; Carcinoma, Pancreatic Ductal; Chymotrypsin; Female; Humans; Imidazoles; Middle Aged; Oncogene Proteins, Fusion; Oximes; Pancreatic Neoplasms; Protein Kinase Inhibitors; Protein Kinases; Pyrazoles; Pyridones; Pyrimidines; Pyrimidinones; Receptor, trkA

Pancreatic cancer is often fatal due to delayed diagnosis and treatment difficulties.. To analyze selected SPINK1, CTRC, CFTR, and PRSS1 gene mutations in cancer tissue and blood samples of patients with pancreatic tumors.. We enrolled 16 consecutive patients diagnosed with pancreatic tumors. We collected cancer tissue, normal pancreatic tissue, and blood samples for genetic tests. The control group consisted of 419 healthy individuals. Peripheral blood samples were collected from all study participants in EDTA-coated tubes.. Out of 16 patients with pancreatic tumors, 12 had pancreatic cancer on microscopic examination (mean age, 60.2 years). The CTRC polymorphism Hetero p.G60=(c.180C>T) was found in 5 patients with pancreatic cancer (41.7% vs. 18.6% in the control group). One patient with pancreatic cancer and a positive family history had the SPINK1 (p.N34S) mutation [8.3% vs. 2.9% (12/419) in the control group]. One patient with pancreatic cancer had the CTRC (p.R254W) mutation [8.3% vs. 1% (4/419) in the control group].. Our preliminary results show that the CTRC polymorphism p.G60= (c.180C>T) is frequent in patients with pancreatic cancer. However, further research is needed to verify our findings.

Topics: Adult; Aged; Chymotrypsin; Female; Genetic Predisposition to Disease; Humans; Male; Middle Aged; Pancreatic Neoplasms; Polymorphism, Genetic

Mutations in the cationic trypsinogen (PRSS1), cystic fibrosis transmembrane conductance regulator (CFTR), serine protease inhibitor Kazal type 1 (SPINK1), and chymotrypsin C (CTRC) genes are associated with an elevated risk for chronic pancreatitis, which is a known risk factor for pancreatic cancer (PC). Therefore, we analyzed whether PRSS1, CFTR, SPINK1, and/or CTRC mutations are associated with pancreatic adenocarcinoma.. The study cohort was composed of 121 PC patients, of whom 74 were classified as having chronic pancreatitis, 102 patients with idiopathic chronic pancreatitis, and 130 as healthy controls. Mutation analyses for the CFTR, SPINK1, PRSS1, and CTRC genes were performed for the presence of the most common mutations.. The frequency of CFTR mutations in patients with PC was not significantly different in comparison with healthy controls and controls with pancreatitis. The SPINK1 mutation frequency was significantly decreased in patients with PC in comparison with patients with idiopathic pancreatitis but varied not significantly in comparison with healthy controls. None of the selected 121 PC samples showed a pancreatitis-predisposing mutation in the PRSS1 or CTRC gene.. Mutations in the genes CFTR, SPINK1, PRSS1, and CTRC do not seem to significantly increase the risk for pancreatic adenocarcinoma.

Topics: Adult; Aged; Aged, 80 and over; Alleles; Carcinoma, Pancreatic Ductal; Carrier Proteins; Chymotrypsin; Cystic Fibrosis Transmembrane Conductance Regulator; DNA Mutational Analysis; DNA, Neoplasm; Female; Genetic Predisposition to Disease; Germany; Humans; Male; Middle Aged; Neoplasm Proteins; Pancreatic Neoplasms; Pancreatitis, Chronic; Precancerous Conditions; Retrospective Studies; Trypsin; Trypsin Inhibitor, Kazal Pancreatic

The diagnosis of chronic pancreatitis remains challenging in early stages of the disease. This report defines the diagnostic criteria useful in the assessment of patients with suspected and established chronic pancreatitis. All current diagnostic procedures are reviewed, and evidence-based statements are provided about their utility and limitations. Diagnostic criteria for chronic pancreatitis are classified as definitive, probable, or insufficient evidence. A diagnostic (STEP-wise; survey, tomography, endoscopy, and pancreas function testing) algorithm is proposed that proceeds from a noninvasive to a more invasive approach. This algorithm maximizes specificity (low false-positive rate) in subjects with chronic abdominal pain and equivocal imaging changes. Furthermore, a nomenclature is suggested to further characterize patients with established chronic pancreatitis based on TIGAR-O (toxic, idiopathic, genetic, autoimmune, recurrent, and obstructive) etiology, gland morphology (Cambridge criteria), and physiologic state (exocrine, endocrine function) for uniformity across future multicenter research collaborations. This guideline will serve as a baseline manuscript that will be modified as new evidence becomes available and our knowledge of chronic pancreatitis improves.

Topics: Calcinosis; Cholangiopancreatography, Magnetic Resonance; Chymotrypsin; Diagnosis, Differential; Disease Progression; Endoscopy, Digestive System; Endosonography; Evidence-Based Medicine; Feces; Humans; Incidence; Pancreatic Elastase; Pancreatic Function Tests; Pancreatic Neoplasms; Pancreatitis, Alcoholic; Pancreatitis, Chronic; Risk Factors; Secretin; Sensitivity and Specificity; Severity of Illness Index; Smoking; Steatorrhea; Tomography, X-Ray Computed

Pancreatic fistula (PF) remains the most serious complication after digestive surgery. It is difficult to prevent because of the inability to visualize the leakage of pancreatic juice during surgery or to evaluate the protease activity of leaked fluid, which is responsible for PF formation.. The fluorescence intensities of a chymotrypsin probe (glutaryl-phenylalanine [corrected] hydroxymethyl rhodamine green with added trypsin) in pancreatic juice and in intestinal or abdominal fluids drained after pancreatic resection were evaluated. The chymotrypsin probe was sprayed on to filter papers that had been placed on the resected pancreatic stump in patients undergoing pancreaticoduodenectomy or central pancreatectomy. The ability of this technique to visualize the leakage of pancreatic juice and predict postoperative PF formation was assessed.. The fluorescence intensity of the chymotrypsin probe in 76 fluid samples correlated positively with amylase levels (r(s) = 0.678, P < 0.001). The fluorescence patterns of the pancreatic stump were classified grossly into the three types: duct (fluorescence signal visualized only on the stump of the main pancreatic duct, 16 patients), diffuse (ductal stump and surrounding pancreatic parenchyma, 7) and negative (no fluorescence signal, 7). Symptomatic PFs developed in 13 of 23 patients with duct- or diffuse-type fluorescence, but in none of the seven patients with negative-type fluorescence (P = 0.008).. The chymotrypsin probe enabled determination of the protease activity in drained pancreatic fluid samples and allowed real-time visualization of pancreatic juice leakage during surgery.

Topics: Aged; Aged, 80 and over; Chymotrypsin; Dipeptides; Female; Fluorescence; Fluorescent Dyes; Humans; Male; Middle Aged; Pancreatectomy; Pancreatic Fistula; Pancreatic Juice; Pancreatic Neoplasms; Pancreaticoduodenectomy; Peptide Hydrolases; Rhodamines

Pancreatic cancer is a malignant cancer with a high mortality rate. The amount of chymotrypsin C in pancreatic cancer cells is only 20% of that found in normal cells. Chymotrypsin C has been reported to be involved in cancer cell apoptosis, but its effect on pancreatic cancer cell migration is unclear. We performed cell migration scratch assays and Transwell experiments, and found that cell migration ability was downregulated in pancreatic cancer Aspc-1 cells that overexpressed chymotrypsin C, whereas the cell migration ability was upregulated in Aspc-1 cells in which chymotrypsin C was suppressed. Two-dimensional fluorescence differential in gel electrophoresis/mass spectrometry method was used to identify the proteins that were differentially expressed in Aspc-1 cells that were transfected with plasmids to induce either overexpression or suppressed expression of chymotrypsin C. Among 26 identified differential proteins, cytokeratin 18 was most obviously correlated with chymotrypsin C expression. Cytokeratin 18 is expressed in developmental tissues in early stages of cancer, and is highly expressed in most carcinomas. We speculated that chymotrypsin C might regulate pancreatic cancer cell migration in relation to cytokeratin 18 expression.

Topics: Base Sequence; Chymotrypsin; DNA Primers; Electrophoresis, Gel, Two-Dimensional; Humans; Neoplasm Metastasis; Pancreatic Neoplasms; Polymerase Chain Reaction; Tumor Cells, Cultured

Acinar cell carcinomas of the pancreas are rare neoplasms. Usually diagnosed at an advanced stage, in general they are large solid pancreatic tumours with an average size of more than 10 cm.. We report 3 cases of acinar cell carcinomas involving the peripancreatic lymph nodes, the liver hilum and the colon respectively, without clinical or pathological evidence of pancreatic tumours. These highly cellular neoplasms showed a predominantly acinar cell differentiation intermingled with a ductal component, with intracellular or extracellular mucin production by at least 25% of tumour cells. In addition, one case showed endocrine differentiation. Diffuse immunoreactivity for acinar enzymes trypsin and chymotrypsin was present in all cases.. The occurrence of acinar cell carcinomas outside the pancreas underlines the notion that acinar cell carcinomas may originate in extrapancreatic sites and probably develop from heterotopic or metaplastic pancreatic foci present along the biliary tract.

Topics: Aged; Carcinoma, Acinar Cell; Chymotrypsin; Humans; Immunohistochemistry; Liver Neoplasms; Lymphatic Metastasis; Male; Middle Aged; Pancreatic Neoplasms; Retroperitoneal Neoplasms; Trypsin

Pancreatic juice is a potential source of proteins associated with pancreatic cancer (PC) due to the proximity of ducts to tumor tissue. Therefore, screening of proteins in pancreatic juice from PC patients may identify new PC biomarkers. We analyzed pancreatic juice from patients with pancreatic diseases including PC, chronic pancreatitis (CP) and simple choledocholithiasis (CDS) by 2-DE. Protein spots from PC patients that changed >2-fold compared with both CP and CDS were selected and identified by mass spectrometry (MS). mRNA levels were measured by QRT-PCR in PC cell lines, PC tissues and adjacent pancreatic normal (PN) tissues. Relationships between mRNA levels in PC tissues and their clinical characteristics and promoter methylation were analyzed in PC cell lines and tissues. We found that four proteins were significantly changed in PC compared to CP and simple CDS. Two proteins were up-regulated, serine proteinase-2 (PRSS2) preproprotein and pancreatic lipase-related protein-1 (PLRP1), and two proteins were down-regulated, chymotrypsinogen B (CTRB) precursor and elastase 3B (ELA3B) preproprotein. In all PC cell lines, PRSS 2 mRNA levels were elevated, while PLRP 1 mRNA was detected in 4/5 cell lines. ELA3B mRNA was undetectable in all cell lines, but CTRB mRNA was detected in 2/5 cell lines. In PC tissues compared to PN, levels of PRSS2 mRNA were significantly higher, ELA3B significantly lower, and PLRP1 and CTRB not significantly different. Elevated PRSS2 mRNA levels correlated with high T stage. The ELA3B gene promoter had higher methylation in PC cell lines and tissues compared with PN tissues, and correlated with low ELA3B gene expression. In conclusion, comparative proteomic analysis of pancreatic juice from PC patients is a powerful method to find new PC biomarkers. Hyperexpression of the PRSS2 gene and hypermethylation of ELA3B gene promoter were associated with PC, raising the possibility of their application as new biomarkers in PC diagnosis and screening.

Topics: Aged; Biomarkers, Tumor; Carcinoma, Pancreatic Ductal; Choledocholithiasis; Chymotrypsin; DNA Methylation; Electrophoresis, Gel, Two-Dimensional; Female; Humans; Intracellular Signaling Peptides and Proteins; Male; Middle Aged; Nuclear Proteins; Pancreas; Pancreatic Elastase; Pancreatic Juice; Pancreatic Neoplasms; Pancreatitis, Chronic; Prognosis; Promoter Regions, Genetic; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; Trypsin; Trypsinogen; Tumor Cells, Cultured

Pancreatic resections for benign diseases may lead to long-term endocrine/exocrine impairment. The aim of this study was to compare postoperative and long-term results after different pancreatic resections for benign disease.. Between 1990 and 1999, 62 patients underwent pancreaticoduodenectomy (PD), 36 atypical resection (AR) and 64 left pancreatectomy (LP) for benign tumours. Exocrine and endocrine pancreatic function was evaluated by 72-h faecal chymotrypsin and oral glucose tolerance test.. The incidence of pancreatic fistula was significantly higher after AR than after LP (11 of 36 versus seven of 64; P = 0.028). The long-term incidence of endocrine pancreatic insufficiency was significantly lower after AR than after PD (P < 0.001). Exocrine insufficiency was more common after PD (P < 0.001) and LP (P = 0.009) than after AR. The probability of developing both endocrine and exocrine insufficiency was higher for PD and LP than for AR (32, 27 and 3 per cent respectively at 1 year; 58, 29 and 3 per cent at 5 years; P < 0.001).. Different pancreatic resections are associated with different risks of developing long-term pancreatic insufficiency. AR represents the best option in terms of long-term endocrine and exocrine function, although it is associated with more postoperative complications.

Topics: Aged; Chymotrypsin; Exocrine Pancreatic Insufficiency; Feces; Female; Follow-Up Studies; Glucose Tolerance Test; Humans; Male; Middle Aged; Pancreatectomy; Pancreatic Neoplasms; Pancreaticoduodenectomy; Risk Factors; Treatment Outcome

Most patients who undergo pylorus-preserving pancreatoduodenectomy (PPPD) are able to gain their weight postoperatively. However, sometimes patients experience a lack of weight gain even at long term after PPPD. The aim of this study was to examine factors influencing a body weight change after PPPD.. In 34 Japanese patients with PPPD, 28 clinical parameters were assessed as possible factors affecting body weight maintenance at long term (1 year) after the operation by univariate and multivariate analyses.. Univariate analysis showed that long operation time (P = 0.02), extended retroperitoneal lymph node dissection (P = 0.0005), intraoperative radiotherapy (P = 0.02), adjuvant postoperative chemotherapy (P = 0.02), histopathological diagnosis of pancreatic cancer (P = 0.02), postoperative ulceration (P = 0.007), and insufficient postoperative pancreatic exocrine function (P = 0.002) were significantly related with the lack of weight gain at long term after PPPD. Multivariate analysis regarding the seven profound factors revealed that the insufficient postoperative pancreatic exocrine function significantly affected the lack of weight gain after PPPD. The use of ordinary amount of pancreatic exocrine enzymes did not influence the weight gain after PPPD (P = 0.23).. In patients refractory to an ordinary amount of medicine, a large dosage of enzymes may be necessary to gain weight after PPPD.

Topics: Adult; Aged; Aged, 80 and over; Body Weight; Chymotrypsin; Female; Humans; Male; Middle Aged; Multivariate Analysis; Pancreas; Pancreatic Neoplasms; Pancreaticoduodenectomy; Pancreatin; Pancreatitis; Weight Gain

Histologic differential diagnosis of acinar cell carcinoma (ACC), mixed acinar-endocrine cell carcinoma (MAEC), and pancreatic endocrine tumors (PET) can be difficult but is important because of differences in their clinical behavior. This study investigates the utility of immunohistochemistry (IHC) in this differential diagnosis using immunohistochemical stains that are available in most laboratories. IHC was performed on paraffin-embedded tissue in ACC (n = 6), MAEC (n = 2), and PET (n = 13), using synaptophysin (SYN), chromogranin (CHR), chymotrypsin (CHY), and alpha-1-antitrypsin (AAT). Electron microscopy (EM) was performed in all cases to confirm the diagnosis. Long-term follow-up and death of disease (DOD) was known in all patients. The ACCs stained as follows: CHY (4/6), AAT (3/6), SYN (4/6); CHR was negative in all cases. Both cases of MAEC stained with CHY, AAT, and SYN (2/2); CHR was negative. PET stained as follows: SYN (13/13), CHR (8/13), CHY (4/13), AAT (5/13). In the ACC/ MAEC group, six of eight patients were DOD at mean follow-up of 11 months. Among the PET, two of 16 patients were DOD at mean follow-up of 37 months. Considerable immunophenotypic overlap exists between ACC, MAEC, and PET. Consequently, one can neither confirm nor rule out a diagnosis of ACC or MAEC using generally available immunohistochemical stains alone. These findings support a role for EM in the evaluation of exocrine and endocrine pancreatic neoplasms.

Topics: Adult; Aged; Aged, 80 and over; alpha 1-Antitrypsin; Carcinoma, Acinar Cell; Chromogranins; Chymotrypsin; Diagnosis, Differential; Endocrine Gland Neoplasms; Female; Follow-Up Studies; Humans; Immunohistochemistry; Male; Microscopy, Electron; Middle Aged; Pancreatic Neoplasms; Synaptophysin; Time Factors

Five cases of pancreatic neoplasms accompanied by production of alpha-fetoprotein (AFP) and serum elevation of this marker are presented, and the better-documented cases of this phenomenon from the literature are reviewed. Four of the cases originated in the orthotopic pancreas, whereas the fifth arose in the pancreatic component of a mediastinal teratoma. The patients were children or young adults. AFP production in pancreatic tumors is closely linked to acinar differentiation, most cases representing either pancreatoblastoma or acinar cell carcinoma. The distinction between these 2 tumors may be difficult because of the many morphologic and immunohistochemical features they share.

Topics: Adolescent; Adult; alpha-Fetoproteins; Carcinoembryonic Antigen; Cell Differentiation; Child; Chromogranins; Chymotrypsin; Female; Humans; Immunohistochemistry; Male; Mediastinal Neoplasms; Pancreatic Neoplasms; Teratoma; Trypsin

Dimethylbenzanthracene (DMBA) induces pancreatic adenocarcinomas in rats 9 months after carcinogen exposure, with precursor lesions (tubular complexes) developing 1 month after initiation of treatment. Because previous studies have suggested an acinar cell of origin for these tumors, we investigated the expression pattern of ductal, acinar, and islet cell markers in these cancers to gain insight into their phenotype and cell of origin. Pancreatic neoplasms were induced in rats by implantation of DMBA into the head of the pancreas. Lesions studied included 10 early tubular complexes (DMBA for 2 weeks), 8 tubular complexes (DMBA for 1 month), and 10 adenocarcinomas (DMBA for 9 months). Normal rat pancreas served as a control. For comparison, 5 human ductal adenocarcinomas were also evaluated. Immunohistochemistry with ductal (keratin, cytokeratin 19, cytokeratin 20), acinar (chymotrypsin), and islet (chromogranin A) cell markers was performed to analyze the tissues. Rat tubular complexes and adenocarcinomas revealed strong expression of keratin, cytokeratin 19, and cytokeratin 20 in the cytoplasm of all neoplastic cells, absence of chymotrypsin, and rare immunoreactivity to chromogranin A. Human adenocarcinomas showed strong expression of keratin and cytokeratin 19 in all neoplastic cells, expression of cytokeratin 20 in 5-20% of cells, and absence of chymotrypsin and chromogranin A. Pancreatic adenocarcinomas induced by DMBA in rats express markers consistent with a ductal phenotype, as observed in human tumors. Ductal marker expression in early tumor stages suggests a ductal cell of origin.

Topics: 9,10-Dimethyl-1,2-benzanthracene; Adenocarcinoma; Aged; Animals; Biomarkers, Tumor; Chromogranin A; Chromogranins; Chymotrypsin; Female; Humans; Immunohistochemistry; Intermediate Filament Proteins; Keratin-20; Keratins; Male; Pancreas; Pancreatic Neoplasms; Precancerous Conditions; Rats; Rats, Sprague-Dawley

The chymotrypsin in the stool test was used to monitor adequate enzymatic substitution in treating exocrine pancreatic insufficiency with 18 patients (16 suffering from chronic pancreatitis and 2 having passed duodenopancreatectomy due to pancreatic cancer). This test helps to identify pancreatic insufficiency and can be successfully used in monitoring the adequate amount of pancreatic substitute, which, we have found, differs from patient to patient. The dosage can be higher in cases of chronic pancreatitis than in those required after duodenopancreatectomy.

Topics: Adult; Chymotrypsin; Exocrine Pancreatic Insufficiency; Feces; Humans; Male; Pancreatic Neoplasms; Pancreaticoduodenectomy; Pancreatin; Postoperative Complications

We have examined the microscopic appearance, immunohistochemical staining properties, and clinical behavior of 28 cases of acinar cell carcinoma of the pancreas. Two of the tumors occurred in children. The adult patients ranged in age from 40 to 81 years (mean, 62 years). Males greatly outnumbered females, and most of the patients were white. Presenting symptoms were nonspecific, and jaundice was infrequent. The frequently reported complications from increased serum lipase levels (i.e., arthralgias and subcutaneous fat necrosis) were present in only 16% of the patients. Grossly, the tumors were relatively circumscribed and fleshy, averaging 10.8 cm, with occasionally extensive hemorrhage and necrosis. Microscopically, the tumors were very cellular and characteristically lacked a desmoplastic stroma. Acinar, solid, trabecular, and glandular patterns of growth were identified; individual tumors were usually mixed. Nuclei were round to oval, with minimal pleomorphism and single prominent nucleoli. Mitotic activity was variable. In general the cytoplasm was moderately abundant, eosinophilic, and granular, but many of the solid tumors had cells with scanty cytoplasm. Characteristic periodic acid-Schiff-positive, diastase-resistant cytoplasmic granules were demonstrated in greater than 90% of the cases, and the butyrate esterase histochemical stain for lipase activity was positive in 73%. Immunohistochemically, there was positivity for trypsin in 100% of the cases, for lipase in 77%, for chymotrypsin in 38%, and for amylase in 31%. A minor endocrine component was recognized with antibodies against chromogranin or islet cell hormones in 42% of the tumors. Ultrastructurally, exocrine secretory features were present, with polarized cells showing microvillilined lumina, abundant rough endoplasmic reticulum, and 125-1,000-nm zymogen-like granules. In addition, many cases showed pleomorphic electron-dense granules measuring up to 3,500 nm and containing fibrillary internal structures. Follow-up information was available in 88% of the cases. Half of the patients had metastatic disease at presentation and an additional 23% subsequently developed metastases, which were usually restricted to the regional lymph nodes and liver. The mean survival for all cases was 18 months, with 1- and 3-year survivals of 57 and 26%, respectively. Patients presenting before age 60 years survived nearly twice as long as older patients did. Stage also influenced prognosis, whereas the histo

Topics: Adult; Aged; Aged, 80 and over; alpha-Amylases; Carcinoma; Cell Division; Cell Nucleus; Child; Chymotrypsin; Cytoplasmic Granules; Diagnosis, Differential; Female; Glucagon; Humans; Immunohistochemistry; Insulin; Keratins; Lipase; Male; Microscopy, Electron; Middle Aged; Mitotic Index; Pancreatic Neoplasms; Prognosis; Trypsin

Fecal isoamylase activity was studied in 93 consecutive patients (26 in the recovery stage of acute pancreatitis, 24 with chronic pancreatitis, 13 with pancreatic cancer, and 30 with other gastrointestinal diseases) and compared with fecal chymotrypsin activity and the results of the secretin test. Seventy-six healthy subjects were studied as controls. Both pancreatic (p)-type and salivary (s)-type isoamylase activities in stool were determined by inhibitor assay as well as cellulose acetate electrophoresis. The mean fecal amylase activity in healthy subjects was 757 +/- 88 IU/g (p-type isoamylase: 77 +/- 2%, s-type isoamylase: 23 +/- 2%). There was a good correlation between fecal p-type isoamylase and chymotrypsin activities (r = 0.625, p less than 0.001). Fecal p-type isoamylase activity in patients with chronic pancreatitis and pancreatic cancer was significantly lower than in healthy subjects (p less than 0.001). Patients with moderate and severe exocrine pancreatic insufficiency as determined by the secretin test had significantly lower fecal p-type isoamylase activity. Daily fat intake did not affect fecal amylase or isoamylase activities. Fecal s-type isoamylase activity in patients with hypoacidity was significantly higher than in patients with hyperacidity, but no difference in fecal p-type isoamylase activity was observed. It is concluded that analysis of fecal isoamylase activity is useful in the assessment of pancreatic function.

Topics: Acute Disease; Adult; Aged; Amylases; Chronic Disease; Chymotrypsin; Dietary Fats; Enterobacteriaceae; Feces; Female; Gastric Acid; Gastrointestinal Diseases; Humans; Isoamylase; Male; Middle Aged; Pancreatic Neoplasms; Pancreatitis; Secretin

Topics: Amylases; Antigens, Tumor-Associated, Carbohydrate; Biomarkers, Tumor; Chymotrypsin; Feces; Humans; Isoamylase; Lipase; Pancreatic Function Tests; Pancreatic Neoplasms; Pancreatitis

Topics: Acute Disease; Animals; Biomarkers, Tumor; Chronic Disease; Chymotrypsin; Clinical Enzyme Tests; Humans; Immunoenzyme Techniques; Isoamylase; Lipase; Pancreatic Elastase; Pancreatic Neoplasms; Pancreatitis; Phospholipases A; Radioimmunoassay; Trypsin

Chromogranin-B (CgB), a secretory granule protein, is normally synthesized in a variety of neuroendocrine tissues, including the pancreatic islet alpha-cells. We have demonstrated that rat CgB is expressed and extensively processed by limited proteolysis in a transplantable glucagonoma tumor line. Eight peptides (fragments 1-8) purified by HPLC from acidic tumor extracts were partially sequenced and showed homology to CgB amino acid sequences deduced from rat, mouse, and human cDNA. Similar peptides were not found in insulinomas of common origin. The determined amino acid sequence represents approximately 35% of the rat precursor CgB. Ten of a total of 231 sequenced residues deviated from the published rat cDNA sequence. The differences were clustered in 3 fragments, suggesting allelic polymorphism. Five of the 8 peptides could be derived from the precursor by processing at paired basic amino acids, but processing N-terminally at a single basic residue was also seen. One peptide equivalent to the previously reported C-terminal CgB (CCB) is released by processing at a tribasic segment. Fragment 1 containing the N-terminal sequence Ala-Pro-Val-Asp represents the actual N-terminus of CgB after removal of the putative signal peptide sequence. All processing sites used in glucagonoma tissue to derive the 8 isolated fragments were conserved between murine and human CgB. At least 3 dibasic sites present in rat, but not human, CgB sequence were actually not used. A previously reported CgB-derived pituitary peptide, GAWK, was further processed at a conserved internal dibasic site to yield fragment 6, indicating alternative processing in different tissues. The small undecapeptide, fragment 7, is 100% conserved among murine and human CgB and, thus, may have an important biological function. We conclude that CgB is extensively processed in glucagonoma tissue by limited proteolysis as prohormones at conserved basic residues. The proglucagon-converting enzymes present in transformed alpha-cells are likely candidates to be involved in tissue-specific CgB processing. Distinct biological activities of any of the CgB-derived fragments remain to be identified.

Topics: Amino Acid Sequence; Animals; Chromatography, High Pressure Liquid; Chromogranin B; Chromogranins; Chymotrypsin; Glucagonoma; Molecular Sequence Data; Neoplasm Transplantation; Pancreatic Neoplasms; Peptide Fragments; Peptide Mapping; Protein Precursors; Rats; Trypsin; Tumor Cells, Cultured

Topics: Animals; Carcinogens; Cell Transformation, Neoplastic; Chymotrypsin; DNA Damage; Glycine max; Humans; Mice; Pancreatic Neoplasms; Protease Inhibitors; Skin Neoplasms; Superoxides; Trypsin Inhibitors

We measured the concentrations of trypsin, elastase, and three anti-proteases-alpha 1-macroglobulin, alpha 1-antitrypsin, and alpha 1-antichymotrypsin-in serum from 10 patients with pancreatic carcinoma. All 10 showed increased elastase and decreased alpha 2-macroglobulin concentrations, nine had increased alpha 1-antichymotrypsin, and eight had increases in alpha 1-antitrypsin and trypsin. Serial studies during chemotherapy of one patient showed that the protease concentrations decreased during treatment but the concentrations of the anti-proteases remained abnormal.

Topics: Aged; alpha 1-Antichymotrypsin; alpha 1-Antitrypsin; alpha-Macroglobulins; Chymotrypsin; Female; Humans; Male; Middle Aged; Pancreatic Elastase; Pancreatic Neoplasms; Trypsin

The possibility that pancreatic secretory abnormalities might precede the appearance of pancreatic neoplasms and thus provide clues to early detection of this malignancy has been investigated in an animal model. Syrian golden hamsters were treated with bis-(2-oxopropyl)-N-nitrosamine on two successive weeks (2 mg/100 g body weight/week). Pancreatic secretions from treated and untreated control animals were studied at approximately monthly intervals. The animals were anesthetized, their pancreatic ducts cannulated, and basal pancreatic juice collected for 30 min. Pancreatic secretion was then stimulated by sequential intravenous injection of secretin (50 ng/100 g) and C-terminal octapeptide of cholecystokinin (4 ng/100 g) 1 hr later. Four consecutive 15-min collections of fluid were made following secretin stimulation and four additional collections after CCK administration. Each collection was examined for volume, total protein, trypsin, chymotrypsin, elastase, arylsulfatase, beta-D-glucuronidase, alpha-D-glucosidase, and leucine naphthylamidase. In addition two trypsinogen variants present in pancreatic secretions were determined. The pancreas and other organs were removed and examined histologically at the end of each experiment. Cytological atypia appeared 3 months, ductal hyperplasia 4 months, and pancreatic neoplasms 6 months after the last injection of carcinogen. Striking decreases in flow rate and output of trypsin and chymotrypsin were observed several months prior to the appearance of histologically recognizable pancreatic tumors. By contrast, output of beta-D-glucuronidase and alpha-D-glucosidase in pancreatic juice increased markedly in the last 2 months preceding the emergence of neoplasms. The diagnostic significance of these premalignant abnormalities is illustrated most dramatically in the form of ratios of lysosomal to digestive enzymes, such as beta-D-glucuronidase-trypsin or alpha-D-glucosidase-chymotrypsin. Highly significant increases in these ratios were observed consistently, not only in hamsters with pancreatic neoplasms, but also in animals with preneoplastic lesions (ductular hyperplasia) which preceded malignancies by about 2 months.

Topics: Age Factors; Animals; Carcinoma, Intraductal, Noninfiltrating; Chymotrypsin; Cricetinae; Male; Mesocricetus; Neoplasms, Experimental; Nitrosamines; Pancreas; Pancreatic Elastase; Pancreatic Juice; Pancreatic Neoplasms; Precancerous Conditions; Trypsin

We have examined the secretogogue responsiveness and the pattern of secretory proteins produced by a transplantable rat pancreatic acinar cell tumor. Dispersed tumor cells were found to discharge secretory proteins in vitro when incubated with hormones that act on four different classes of receptors: carbamylcholine, caerulein, secretin-vasoactive intestinal peptide, and bombesin. With all hormones tested, maximal discharge from tumor cells was only about one-half that of control pancreatic lobules, but occurred at the same dose optima except for secretin, whose dose optimum was 10-fold higher. Biochemical analysis of secretory proteins discharged by the tumor cells was carried out by crossed immunoelectrophoresis and by two-dimensional isoelectric focusing-SDS polyacrylamide gel electrophoresis. To establish a baseline for comparison, secretory proteins from normal rat pancreas were identified according to enzymatic activity and correlated with migration position on two-dimensional gels. Our results indicate that a group of basic polypeptides including proelastase, basic trypsinogen, basic chymotrypsinogen, and ribonuclease, two out of three forms of procarboxypeptidase B, and the major lipase species were greatly reduced or absent in tumor cell secretion. In contrast, the amount of acidic chymotrypsinogen was notably increased compared with normal acinar cells. Although the acinar tumor cells are highly differentiated cytologically and express functional receptors for several classes of pancreatic secretagogues, they show quantitative and qualitative differences when compared with normal pancreas with regard to their production of secretory proteins.

Topics: Amylases; Animals; Carboxypeptidase B; Carboxypeptidases; Chymotrypsin; Hydrolases; Lipase; Neoplasms, Experimental; Pancreas; Pancreatic Elastase; Pancreatic Neoplasms; Rats; Rats, Inbred F344; Ribonucleases; Trypsin

The cellular localization of alpha-1-antichymotrypsin (alpha 1-ACT) was studied immunohistochemically using rabbit HRP-labeled Fab' against human alpha 1-ACT. alpha 1-ACT was found in cell nuclei of carcinomas of the stomach, liver, breast, pancreas and leiomyosarcoma and in cell nuclei of lymphoid cells infiltrated into the stomach carcinoma mass. alpha 1-ACT was not found in carcinoma cells of the colon, uterus, rectum or esophagus, or in lymphoid cells infiltrated into the rectal carcinoma mass or into inflammatory regions such as gastric ulcers or appendicitis. Further, alpha 1-ACT was not found in normal cells around the carcinoma mass or in normal tissues.

Topics: alpha 1-Antichymotrypsin; Breast Neoplasms; Carcinoma; Cell Nucleus; Chymotrypsin; Humans; Immunologic Techniques; Leiomyosarcoma; Liver Neoplasms; Lymphoid Tissue; Neoplasms; Pancreatic Neoplasms; Stomach Neoplasms; Trypsin Inhibitors

Topics: Chymotrypsin; Clinical Enzyme Tests; Duodenum; Humans; Intestinal Secretions; Pancreatic Neoplasms

Topics: Chymotrypsin; Feces; Humans; Pancreatic Diseases; Pancreatic Neoplasms; Pancreatitis

The diagnostic aids of acute pancreatitis include the clinical presentation, laboratory investigations and abdominal sonography. The assessment of amylase creatinin clearance ratio is not superior to simple amylase estimations in identifying unspecific hyperamylasemias apart from acute pancreatitis. The management of acute pancreatitis consists of a standardized basic treatment which does not depend on the degree of the severity of the disease and supplementary measures which are adjusted to the degree of severity and complications. In case of chronic pancreatitis a variety of indirect and direct morphological and functional examinations are available. The diagnostic safety of all procedures--each taken by its own--is below 90%; however, the combined use has to be adjusted to the severity of the symptoms suspicious of pancreatis disease. The therapeutic goal includes the conservative management of the painful recurrences to achieve transmission into the final stage of the disease which presents only minor symptoms. Operation has to be considered in case of untreatable pain and local complications. The obstruction of the pancreatic duct by means of synthetic glue instillations is a hopeful approach.

Topics: Acute Disease; Calcitonin; Carcinoma; Chronic Disease; Chymotrypsin; Humans; Hypocalcemia; Middle Aged; Pancreas; Pancreatic Neoplasms; Pancreatitis; Tomography, X-Ray Computed; Ultrasonography

The pancreas can be studied for obstructive disease by measuring serum lipase levels in the two stage provocative test. The test is nonspecific but noninvasive and applicable to all stages of pancreatic diseases. In this test, the pancreas is stimulated twice in two hour intervals before measuring the serum enzyme levels: first, with pancreozyin and secretin--the stage 1 test and, second, with pancreozymin, secretin, betazole hydrochloride and morphine sulfate--the stage 2 test. Among the pancreatic enzymes measured, lipase was most reliable. Serum lipase level elevation in the stage 1 test indicates a pancreatic abnormality and it completes the test. Patients who fail to respond to the stage 1 test have either a normal pancreas or pancreatic insufficiency and need the stage 2 test for differential diagnosis. In the stage 2 test, the serum lipase level is elevated in patients with a normal pancreas but not in those with pancreatic insufficiency. As a preliminary study, ten patients with carcinoma of the pancreas, two with pancreatitis and ten in the control group were studied. All patients with a known pancreatic disease demonstrated an abnormality in the test. Two of ten in the control group also had abnormal results. The two stage provocative test may be used prior to undertaking more invasive examinations, such as an arteriogram, in patients who are suspected of having pancreatic disease, yet other tests have failed to indicate it.

Topics: Amylases; Betazole; Cholecystokinin; Chymotrypsin; Clinical Enzyme Tests; Female; Humans; Lipase; Male; Morphine; Pancreatic Diseases; Pancreatic Neoplasms; Pancreatitis; Secretin; Trypsin

Topics: Adult; Amylases; Carboxypeptidases; Chronic Disease; Chymotrypsin; Clinical Enzyme Tests; Deoxyribonucleases; Humans; Lipase; Liver Cirrhosis; Pancreas; Pancreatic Diseases; Pancreatic Neoplasms; Pancreatitis; Ribonucleases; Trypsin

Enteropeptidase, trypsin, and chymotrypsin activity in basal and secretin-stimulated duodenal juice of 20 normal adult volunteers and 15 patients with gastrotestinal disease were determined. All enzyme concentrations showed skew distributions, but fluctuations in the secretin-stimulated juices were less pronouced than in the basal secretions. Secretin administration had no influence on the release of enteropeptidase from human duodenal mucosa, but resulted in a very small increase in secretion of pancreatic enzymes. Six out of seven patients with chronic alcoholic pancreatitis or cancer of the pancreas exhibited highly significant elevations of enteropeptidase in their basal as well as secretin-stimulated duodenal juice. It is suggested that raised luminal enteropeptidase activity may be the result of pancreatic insufficiency or elevated blood glucagon concentrations.

Topics: Adult; Child; Chymotrypsin; Duodenum; Endopeptidases; Enteropeptidase; Gastrointestinal Diseases; Humans; Infant; Middle Aged; Pancreatic Juice; Pancreatic Neoplasms; Pancreatitis; Secretin; Trypsin

Pancreatic secretory abnormalities develop in most persons with pancreatic cancer and have been attributed to ductal obstruction. These experiments investigated whether abnormal secretion results instead from carcinogen-induced changes in the secreting cells. Fifty male Syrian Golden hamsters (40 to 100 grams) received weekly injections of di-isopropyl-nitrosamine (250 mg/kg, subcutaneously), and survivors and age-matched controls were studied after 3.5 to 6.5 months of treatment. Pancreatic secretion was stimulated by secretin or cholecystokinin (2 units/kg, intravenously, as a bolus). After each stimulus four 15-minute collections of pancreatic juice were analyzed for HCO3- and Cl- or total protein, amylase, trypsin, and chymotrypsin. The organs were examined histologically. Pancreatic ductal adenocarcinoma developed in 30% of the animals at 5 months, 56% at 5.5 months, and 100% at 6.5 months. The animals without cancer either had hyperplasia of the duct epithelium or were histologically normal. The histologic appearance of acinar tissue and protein secretion were normal in all groups. The tumors did not obstruct the major ducts. In all treated animals the pancreatic secretory response to secretin was of low volume, low maximal [HCO3-] and HCO3- output, and low [Cl- + HCO3-]; these changes progressed with time. The secretory abnormalities antedated the appearance of the neoplasms and were not caused by obstruction.

Topics: Amylases; Animals; Cholecystokinin; Chymotrypsin; Cricetinae; Electrolytes; Male; Mesocricetus; Pancreas; Pancreatic Ducts; Pancreatic Juice; Pancreatic Neoplasms; Proteins; Secretin; Trypsin

Topics: Adult; Aged; Chronic Disease; Chymotrypsin; Feces; Female; Humans; Male; Middle Aged; Neoplasm Metastasis; Pancreatic Diseases; Pancreatic Neoplasms; Pancreatitis

1. A simple, highly sensitive, specific fluorometric method for the determination of chymotrypsin is described. 2. The new substrate utilized in this assay, N-glutaryl-glycyl-glycyl-l-phenylalanine beta-naphthylamide (GGPNA), is readily soluble in water, stable and highly specific for chymotrypsin. It is not degraded by a large excess of carboxypeptidase B, elastase, thrombin or plasmin and is virtually resistant to trypsin. 3. GGPNA is extremely sensitive to the action of chymotrypsin and permits detection of enzyme concentrations as low as 1 ng/ml. Linearity between enzyme concentration and fluorescence produced is maintained up to at least 3000 ng/ml. 4. alpha2-Macroglobulin-bound chymotrypsin hydrolyzes GGPNA at a rate about 2/3 of that exhibited by the free enzyme. 5. Bile pigments in amounts normally found in duodenal juice or traces of blood do not interfere with the assay. 6. GG PNA which releases beta-naphthylamine upon hydrolysis is suitable also for colorimetric and histological determination of chymotrypsin.

Topics: Bilirubin; Chronic Disease; Chymotrypsin; Hemoglobins; Humans; Hydrogen-Ion Concentration; Kinetics; Macroglobulins; Methods; Microchemistry; Naphthols; Oligopeptides; Pancreatic Neoplasms; Pancreatitis; Protein Binding; Spectrometry, Fluorescence

Pancreatico-duodenectomy was performed in 11 patients for malignant or inflammatory tumours of the head of the pancreas or the region of the papilla. Digestive and endocrine functions were determined after the operation. In all cases faecal fat values were abnormal, indicating a 90% loss of pancreas. 14C-exhalation measurement, chymotrypsin determination in stool, and amylose tolerance test were also performed. Oral glucose-tolerance tests with plasma-insulin measurement indicated asymptomatic diabetes mellitus in the majority of patients. Two patients whose diabetes was controlled by tablets before the operation required insulin treatment afterwards. A decreased serum-gastrin level proved the existence of gastric and extragastric sources of gastrin.

Topics: Blood Glucose; Body Weight; Chymotrypsin; Duodenum; Feces; Gastric Juice; Gastric Mucosa; Glucose Tolerance Test; Humans; Insulin; Malabsorption Syndromes; Pancreas; Pancreatic Neoplasms; Postoperative Complications; Time Factors; Xylose

Topics: Cholecystokinin; Chymotrypsin; Duodenum; Endoscopy; Humans; Intubation, Gastrointestinal; Pancreas; Pancreatic Diseases; Pancreatic Juice; Pancreatic Neoplasms; Radiography; Trypsin

Topics: Amylases; Bicarbonates; Bile Pigments; Blood Glucose; Blood Protein Electrophoresis; Chymotrypsin; Duodenal Diseases; Humans; Lipase; Pancreatic Diseases; Pancreatic Ducts; Pancreatic Juice; Pancreatic Neoplasms; Pancreatitis; Stomach Diseases; Trypsin

Topics: Animals; Carboxypeptidases; Cattle; Chymotrypsin; Chymotrypsinogen; Enzyme Activation; Enzyme Precursors; Humans; Male; Middle Aged; Pancreatic Ducts; Pancreatic Elastase; Pancreatic Juice; Pancreatic Neoplasms; Peptide Hydrolases; Phospholipases; Proteins; Time Factors; Trypsin; Trypsin Inhibitors; Trypsinogen

Topics: Amylases; Cholecystokinin; Chronic Disease; Chymotrypsin; Female; Humans; Lipase; Male; Pancreas; Pancreatic Juice; Pancreatic Neoplasms; Pancreatitis; Secretin; Stimulation, Chemical; Trypsin

Topics: Buffers; Chronic Disease; Chymotrypsin; Clinical Enzyme Tests; Feces; Humans; Indicators and Reagents; Methods; Pancreas; Pancreatic Diseases; Pancreatic Neoplasms; Pancreatitis; Postoperative Complications

Topics: Cholecystokinin; Chymotrypsin; Duodenum; Humans; Pancreas; Pancreatic Diseases; Pancreatic Neoplasms; Pancreatitis; Secretin; Trypsin

Trypsin and chymotrypsin concentrations were determined in 180 spot stool specimens from 110 control patients in hospital. The lower limit of normality for each enzyme was placed at the 5% level: 95% of this population excreted feces containing more than 100 mug. of chymotrypsin and 30 mug. of trypsin per g. of feces. Chymotrypsin concentrations appeared to be a more reliable guide to pancreatic function than trypsin concentrations.Fecal chymotrypsin concentrations were subnormal in five patients with chronic pancreatitis, borderline in one patient with relapsing pancreatitis, subnormal in one patient after pancreatectomy, and subnormal in five of nine with carcinoma of the pancreas. Subnormal concentrations of fecal chymotrypsin were found in seven of 21 patients with chronic liver disease related to alcoholism, eight of 32 with a partial gastrectomy, three of 10 with adult celiac disease and five of 16 with psoriasis.It appears that the determination of fecal chymotrypsin concentrations provides a valuable screening test for pancreatic exocrine deficiency. However, normal results may be found in some patients with pancreatic disease and subnormal values may occur in some patients with other conditions.

Topics: Alcoholism; Chymotrypsin; Feces; Humans; Liver Cirrhosis; Malabsorption Syndromes; Pancreatic Diseases; Pancreatic Neoplasms; Pancreatitis; Skin Diseases; Trypsin

Topics: Adult; Aged; Caseins; Chymotrypsin; Feces; Female; Humans; Iodine Isotopes; Male; Methods; Middle Aged; Pancreatic Neoplasms; Pancreatitis; Peptide Hydrolases; Trypsin

The interrelationships of proteolytic enzymes and amylase have been studied in the duodenal aspirate obtained from subjects with normal and abnormal pancreatic function during stimulation with secretin and pancreozymin. While the relationship of trypsin to chymotrypsin was independent of stimulus and presence of pancreatic disease the ratio of proteolytic enzymes to amylase rose when the degree of stimulation of the pancreas was increased. Patients with recent acute pancreatitis and with chronic pancreatitis tended to have more severe impairment of secretion of proteolytic enzymes than of amylase. In routine tests of pancreatic function both proteolytic and non-proteolytic enzymes should be measured, both because an abnormal ratio may be of diagnostic significance and because the two different groups of enzymes provide mutual checks of the secretory capacity of pancreatic enzymes.

Topics: Amylases; Cholecystokinin; Chymotrypsin; Duodenal Ulcer; Duodenum; Humans; Pancreas; Pancreatic Neoplasms; Pancreatitis; Peptide Hydrolases; Secretin; Trypsin

Topics: Cardiovascular Diseases; Cholestasis; Chymotrypsin; Diabetes Mellitus; Gastritis; Humans; Liver Cirrhosis; Liver Neoplasms; Lung Diseases; Pancreatic Neoplasms; Pancreatitis; Trypsin Inhibitors

Topics: Acute Disease; Amylases; Chronic Disease; Chymotrypsin; Diagnosis, Differential; Feces; Gastric Juice; Humans; Lipase; Lipids; Pancreatic Diseases; Pancreatic Neoplasms; Pancreatitis; Preoperative Care; Trypsin

Topics: Amylases; Chymotrypsin; Clinical Enzyme Tests; Duodenum; Female; Humans; Hydrogen-Ion Concentration; Inhalation; Intestinal Secretions; Lipase; Male; Methods; Pancreatic Juice; Pancreatic Neoplasms; Pancreatitis; Trypsin

Topics: Aged; Amylases; Bicarbonates; Blood Glucose; Blood Proteins; Cholecystokinin; Chymotrypsin; Diet Therapy; Female; Humans; Injections, Intravenous; Intestinal Absorption; Intestinal Secretions; Iodine Isotopes; Jejunum; Lipids; Pancreatectomy; Pancreatic Neoplasms; Secretin; Serum Albumin, Radio-Iodinated; Triolein; Trypsin

Topics: Animals; Anura; Biological Assay; Carcinoma, Bronchogenic; Chromatography, Gel; Chromatography, Ion Exchange; Chymotrypsin; Diuresis; Hormones, Ectopic; Humans; Hyponatremia; Liver Neoplasms; Lymphatic Metastasis; Neoplasm Metastasis; Pancreatic Neoplasms; Thioglycolates; Trypsin; Vasopressins

Topics: Cholecystokinin; Chymotrypsin; Feces; Humans; Pancreatic Neoplasms; Secretin

Topics: Adult; Aged; Cholecystokinin; Chymotrypsin; Feces; Female; Humans; Male; Middle Aged; Pancreatic Neoplasms; Secretin; Trypsin

Topics: Adolescent; Child; Cholelithiasis; Chymotrypsin; Clinical Enzyme Tests; Cystic Fibrosis; Diagnosis; Exocrine Pancreatic Insufficiency; Feces; Gastrointestinal Diseases; Geriatrics; Humans; Infant; Intubation; Intubation, Gastrointestinal; Liver Diseases; Pancreatic Neoplasms; Pancreatitis; Trypsin

Topics: Chymotrypsin; Exocrine Pancreatic Insufficiency; Feces; Pancreatic Neoplasms; Pancreatitis; Trypsin