bromochloroacetic-acid and Pancreatitis--Chronic

Topics: Carrier Proteins; Cystic Fibrosis Transmembrane Conductance Regulator; Cytochrome P-450 CYP2E1; Genetic Linkage; Genetic Markers; HLA-DR Antigens; HLA-DRB1 Chains; Humans; Keratin-8; Keratins; Mutation; Pancreatitis, Chronic; Polymorphism, Genetic; Trypsin Inhibitor, Kazal Pancreatic; Trypsinogen

Islet autotransplant patients represent excellent subjects to assess the posttransplant impact of islet precursors, as chronic pancreatitis (CP) causes an elevation of ductal cells, pancreatic precursors cells, and hormone-positive acinar cells. The relationship between these cell types and autograft outcomes should be more apparent than would be the case in the context of an allograft program with confounding immunological variables. To improve diabetic control following total pancreatectomy for CP, nonpurified islets were autotransplanted into the liver. Pancreas specimens were recovered from 23 patients and stained for antigens including: insulin, glucagon, cytokeratin 19, cytokeratin 7, and PDX-1. In line with previous reports, the prevalence of ductal cells, non-islet endocrine cells and non-islet PDX-1-expressing cells was significantly higher in CP glands compared with normal pancreata. When correlating follow-up data (i.e., fasting and stimulated C-peptide/glucose levels and HbA1c%) with pancreas immunoreactivity, high levels of ductal cells, non-islet PDX-1-positive cells, and non-islet glucagon-positive cells were associated with superior outcomes, detectable up to 2 years posttransplant. To conclude, the acinar parenchyma and ductal epithelium of the CP pancreas show an upregulation of both endocrine and pre-endocrine cell types, which appear to have a positive effect on islet graft outcomes in autotransplantation setting.

Topics: Biomarkers; Epithelial Cells; Glucagon; Homeodomain Proteins; Humans; Insulin; Islets of Langerhans; Islets of Langerhans Transplantation; Keratins; Pancreatic Ducts; Pancreatitis, Chronic; Stem Cells; Trans-Activators; Transplantation, Autologous

Pancreatic endocrine tumours (PET) containing ductules are an uncommon histological variant. Considerable conjecture surrounds the origin and histogenesis of the ductules. Opinions range from the ductules being an inherent part of the tumour, to others who feel they are merely entrapped. A study of 21 cases of this variant was undertaken with particular attention paid to the distribution and morphology of the ductules, the presence of entrapped acinar tissue and the surrounding uninvolved pancreatic tissue.. Twenty-one cases were detailed occurring in either gender equally and with a wide age range (19-85 years). All cases, except one, were sporadic, the vast majority were located in the tail and were of small size (less than 2.0 cm). All cases were typified by stromal fibrosis, either diffuse (15) or in the form of septae (6). Embedded within the fibrous tissue were ductular structures, some of which were dilated and ectatic. The ductules were centrally located (5), at the periphery of the tumour (9) or diffusely scattered throughout the lesion (7). All cases showed ductulo-insular complexes. Insulin was demonstrated in 15 immunohistochemically.. It is likely that in some cases the ductules are entrapped as the tumour grows into surrounding normal pancreatic tissue and the ductular proliferation is a secondary phenomenon. In a proportion of cases, the ductules are likely to be a part of the tumour arising as part of focal chronic inflammation or as a result of the growth factor effects of insulin, in cases associated with insulin production. There is nothing to suggest that the ductules confer any special biological characteristics to the PET and are merely a histological nuance. However, some cases may have a dominant tubular component, which could present problems at frozen section where the association with fibrosis may invoke a mistaken diagnosis of pancreatic ductal adenocarcinoma or chronic pancreatitis.

Topics: Adenocarcinoma; Adult; Aged; Aged, 80 and over; Biomarkers; Carcinoma, Islet Cell; Carcinoma, Pancreatic Ductal; Diagnosis, Differential; Female; Fibrosis; Humans; Immunohistochemistry; Insulin; Islets of Langerhans; Keratins; Male; Middle Aged; Pancreatic Ducts; Pancreatic Neoplasms; Pancreatitis, Chronic