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PubMed2006

Ectopic pancreas formation in Hes1 -knockout mice reveals plasticity of endodermal progenitors of the gut, bile duct, and pancreas.

Ectopic pancreas is a developmental anomaly occasionally found in humans. Hes1, a main effector of Notch signaling, regulates the fate and differentiation of many cell types during development. To gain insights into the role of the Notch pathway in pancreatic fate determination, we combined the use of Hes1-knockout mice and lineage tracing employing the Cre/loxP system to specifically mark pancreatic precursor cells and their progeny in Ptf1a-cre and Rosa26 reporter mice. We show that inactivation of Hes1 induces misexpression of Ptf1a in discrete regions of the primitive stomach and duodenum and throughout the common bile duct. All ectopic Ptf1a-expressing cells were reprogrammed, or transcommitted, to multipotent pancreatic progenitor status and subsequently differentiated into mature pancreatic exocrine, endocrine, and duct cells. This process recapitulated normal pancreatogenesis in terms of morphological and genetic features. Furthermore, analysis of Hes1/Ptf1a double mutants revealed that ectopic Ptf1a-cre lineage-labeled cells adopted the fate of region-appropriate gut epithelium or endocrine cells similarly to Ptf1a-inactivated cells in the native pancreatic buds. Our data demonstrate that the Hes1-mediated Notch pathway is required for region-appropriate specification of pancreas in the developing foregut endoderm through regulation of Ptf1a expression, providing novel insight into the pathogenesis of ectopic pancreas development in a mouse model.

Animals↗

PubMed2002

Pancreas duodenum homeobox-1 regulates pancreas development during embryogenesis and islet cell function in adulthood.

Pancreas duodenum homeobox-1 (PDX-1) (also known as insulin promoter factor-1, islet/duodenum homeobox-1, somatostatin transactivating factor-1, insulin upstream factor-1 and glucose-sensitive factor) is a transcription factor encoded by a Hox-like homeodomain gene. In humans and other animal species, the embryonic development of the pancreas requires PDX-1, as demonstrated by the identification of an individual with pancreatic agenesis resulting from a mutation that impaired the transcription of a functionally active PDX-1 protein. In adult subjects, PDX-1 is essential for normal pancreatic islet function as suggested by its regulatory action on the expression of a number of pancreatic genes, including insulin, somatostatin, islet amyloid polypeptide, the glucose transporter type 2 and glucokinase. Furthermore, heterozygous mutations of PDX-1 have been linked to a type of autosomal dominant form of diabetes mellitus known as maturity onset diabetes of the young type 4. The dual action of PDX-1, as a differentiation factor during embryogenesis and as a regulator of islet cell physiology in mature islet cells, underscores the unique role of PDX-1 in health and disease of the human endocrine pancreas.

Amino Acid Sequence↗

PubMed1999

Effects of pancreas transplantation on late complications of diabetes and metabolic effects of pancreas and islet transplantation.

Pancreas transplantation has become an accepted therapeutic approach to treat insulin-dependent diabetes mellitus, successfully restoring normoglycemia. In contrast, islet transplantation is still in the experimental phase, only a few operations having being performed world-wide. The aim of this review is to analyze the effects of pancreas transplantation on the late complications of diabetes and to report the endocrino-metabolic effects of pancreas and islet transplantation.

Blood Glucose↗

PubMed2005

[Theories and techniques for resection of the extrapancreatic nerve plexus in the head of the pancreas during a Whipple procedure for carcinoma of the pancreas--suggestions from the perspective of surgical anatomy and pathology].

Although various therapeutic modalities for carcinoma of the pancreas are available, "curative (R0) resection" is the most important. Thus, the aim of surgery for carcinoma of the pancreas is local complete resection of the carcinoma. We offer two suggestions for complete resection of carcinoma of the pancreas, which shows a strong invasive tendency around nerve fibers, during a Whipple procedure. 1. En bloc resection of the right side of nerve plexus of the superior mesenteric artery and the first and second nerve plexus of the pancreatic head should be performed. It is easy to perform this procedure when the superior mesenteric artery should be moved to the right side of the superior mesenteric vein through under this vein. 2. The entire cut end of the nerve plexus should be investigated during the operation using frozen specimens and confirmed to be negative for cancer. If the cut end is positive for cancer, additional resection of the nerve plexus should be performed to achieve curative resection. The reason is that it is impossible to completely investigate positive or negative carcinoma in the cut end of the nerve plexus after surgery, since the cut end is long and some specimens are deformed by formalin fixation.

Humans↗

PubMed1990

[Cancer of the pancreas. II. The histological forms and local complications of carcinoma of the pancreas].

A detailed study of the histologic forms and local complications of pancreas cancer is made. Based on ample pathologic case material (25,589 sections for 25 years), the prevailing number of cases of pancreas cancer had histologic characteristics of adenocarcinoma, which is in keeping with the standpoint that glandular carcinoma is the most common form of pancreas cancer. Next in incidence were histologic forms of nondifferentiated scirrhous carcinoma and gelatinous cancer of the gland.

Carcinoma↗

PubMed1980

[Diseases of the exocrine pancreas in infants and children. A review. 3. Pseudocysts, cysts, tumors: functional disorders of the exocrine pancreas secretion; pseudo-pancreatic insufficiency].

The aim of the present work is to provide a new classification of the exocrine pancreatic diseases in childhood by means of a simple and practicable scheme which is in line with the recognized classification of Internal Medicine. The article presents a definite distinction between organic diseases of the pancreas -- such as deformities, congenital insufficiences, pancreatitis, cysts and tumors -- functional disturbances of the pancreas secretion and pseudo-pancreas insufficiency caused by extrapancreatic factors. New investigative methods help to distinguish between various disorders encountered.

Adenoma, Islet Cell↗

PubMed1994

Cyclosporine challenge in the decision of combined kidney-pancreas versus solitary pancreas transplantation.

Combined kidney-pancreas transplantation has become the treatment of choice for many patients with end-stage diabetic nephropathy. Pancreas transplantation (PTx) alone is an option for type I diabetic patients without end-stage diabetic nephropathy. Knowledge of factors contributing to or predicting the rate of renal deterioration (including the effect of CsA on the patient's renal function before transplantation) is necessary to determine candidacy for either kidney-pancreas transplantation or PTx alone. To address this issue, we selected 12 pre-uremic patients with creatinine clearances (CrCl) above 40 ml/min and less than 100 ml/min to participate in a 6-week oral CsA challenge test. Serum chemistries, including serum creatinine (SCr) and CsA level, were measured weekly. Urinary protein and CrCl were measured at 0, 2, 4, and 6 weeks. Glomerular filtration rate (GFR) (by 125I-sodium iothalamate clearance) was measured at 0, 3, and 6 weeks. All patients initially received oral CsA at 10 mg/kg/day in 2 divided doses. Doses were adjusted to maintain a 12-hr trough level of 500-1000 ng/ml using a whole blood polyclonal TDX assay. Data are presented as mean +/- SEM and as box-plot graphs. One patient was a CsA challenge test failure because SCr exceeded 3.0 mg/dl despite a reduction in CsA dose and level. Therefore, this patient was not a candidate for PTx alone and was excluded from further analysis. Among the 11 nonfailures, the mean CsA level at 6 weeks was 640 +/- 76 ng/ml. SCr increased from 1.2 +/- 0.1 mg/dl to 1.6 +/- 0.1 mg/dl (33% increase) (P = 0.0001). CrCl decreased from 82 +/- 9 ml/min to 63 +/- 8 ml/min (24% decrease) (P = 0.03). GFR decreased from 95 +/- 15 ml/min to 70 +/- 10 ml/min (26% decrease) (P = 0.009). CrCl and GFR did not differ from one another at 0 and 6 weeks (r = 0.77 and 0.98; P = 0.3 and 0.7, respectively). Urinary protein decreased from 1.0 +/- 0.3 g/day to 0.7 +/- 0.3 g/day at both 4 and 6 weeks (P = 0.03 and 0.06, respectively). Three of the 11 patients have not yet received transplants. Eight patients subsequently received PTx alone and were followed prospectively. Two allografts were lost early to rejection. Six were followed from 5 to 19 months after PTx alone. Serum creatinine and CrCL measurements during the CsA challenge test predicted post-PTx levels: SCr 1.6 +/- 0.1 vs. 1.7 +/- 0.3 mg/dl, P = 0.48, and CrCl 68 +/- 10 vs. 53 +/- 3 ml/min, P = 0.17, respectively.

Adult↗

PubMed1997

The arterial blood supply of the pancreas: a review. IV. The anterior inferior and posterior pancreaticoduodenal aa., and minor sources of blood supply for the head of the pancreas. An anatomical review and radiologic study.

The present article is the fourth part of a comprehensive review of the arterial blood supply of the pancreas and completes the study of the arterial vascularization of the pancreatic head dealing with the anterior inferior and posterior inferior pancreaticoduodenal aa. and with some minor sources of blood supply not involving the classical system of the pancreaticoduodenal arches. The aim of this review is to summarise the anatomical studies, starting from Haller's reports, and to supply, as far as possible with original material, angiographic evidence for the classic anatomical concepts. For this purpose, 1015 selective angiographs (celiac trunk and its branches, superior mesenteric a.) were taken from the angiographic archives of the Institutes of Radiology of Siena, Rome (Catholic University), and Perugia. These demonstrated the anterior inferior pancreaticoduodenal a., present in most instances, as arising from the inferior pancreaticoduodenal a., from a common trunk with the posterior inferior pancreaticoduodenal a. and the 1st jejunal a., from the 1st jejunal a. or from the superior mesenteric a.; on the other hand, the posterior inferior pancreaticoduodenal a. was more variable, originating from the inferior pancreaticoduodenal a., from a common trunk with the anterior inferior pancreaticoduodenal a. and the 1st jejunal a., from the superior mesenteric a., from the dorsal pancreatic a., or from a right accessory hepatic a. coming from the superior mesenteric a. In addition, minor branches to the head of the pancreas arose from the gastroduodenal a., the dorsal pancreatic a., the common hepatic a. and the inferior right phrenic a. Other origins of the inferior pancreaticoduodenal aa. previously reported, but not angiographically detectable with certainty, as well as further minor sources of blood supply to the head of the pancreas, have been listed. The differing opinions regarding the incidence of the various ways the inferior pancreaticoduodenal aa. arise are discussed and an attempt is made to explain the variability of the vascular anatomy of the pancreatic head on embryologic grounds.

Arteries↗

PubMed1989

On the nature of the galanin action on the endocrine pancreas: studies with six galanin fragments in the perfused dog pancreas.

Galanin, a 29 amino acid peptide, inhibits insulin and somatostatin secretion from the isolated, perfused dog pancreas. To assess the nature of the influences of galanin on the endocrine pancreas, we examined the effects of porcine galanin and six different galanin analogues at the equimolar concentration of 1 nmol/l on the hormone release from the isolated, perfused dog pancreas. It was found that galanin2-29 (by 75 +/- 4%), like the native galanin1-29 (by 90 +/- 3%) potently inhibited insulin secretion (p less than 0.001). In contrast, galanin3-29 did not significantly affect insulin secretion. This indicates that removal of the two N-terminal amino acids markedly reduces the potency of galanin. Also, the replacement of the amino acid number 2 (Trp) by Tyr or Phe was followed by a loss of the insulin lowering effect of galanin at this dose level. Likewise, galanin10-29 had no significant effect on insulin secretion. In contrast, the C-terminally deleted galanin1-15 significantly inhibited insulin secretion (by 24 +/- 5%; p less than 0.01), though with a lower potency than did native galanin (p less than 0.05). Consequently, the C-terminal end of galanin is also of importance for the effect. Somatostatin secretion was inhibited by galanin (p less than 0.001), but not by any of the other investigated peptides. Glucagon secretion was not affected by galanin. It is concluded that the two N-terminal amino acids of galanin are essential for the inhibitory action on the insulin secretion.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acid Sequence↗

PubMed2002

[Chronic pancreatitis in the ventral pancreas in pancreas divisum].

Pancreas divisum, partial or non fusion of the dorsal and ventral pancreatic ductal system, affects up to 10 percent of the population. Approximately 25 percent of patients with pancreas divisum will develop complications such as recurrent pancreatitis. Surgical and endoscopic therapy usually include minor papilla sphincterotomy or sphincteroplasty to facilitate drainage of the dorsal ductal system. The following case represents an unusual complication of the pancreas divisum with primarily ventral duct disease and pancreaticolithiasis.

Adult↗

PubMed1990

[Cancer of the pancreas. V. The characteristics of the histological forms and of local complications in carcinoma of the pancreas in both sexes].

A study of ample postmortem case material of 25589 autopsies for a period of 25 years (1963-1987) revealed great diversity of the histologic forms of pancreas cancer both in males and in females, associated with numerous local complications (infiltration in adjacent organs). The major number of cases--144 (34.4 per cent of the total number) had histologic characteristics of adenocarcinoma: 88 cases in males (32.1 per cent) and 56 in females (38.6 per cent). Second in incidence--109 cases (26 per cent of the total number) had histologic characteristics of adenoscirrhous cancer--77 in males (28.1 per cent) and 32 in females (22.1 per cent). This is in keeping with the concept that adenocarcinoma is the most common from of pancreas cancer. The next most common forms are adenocarcinoma combined with nondifferentiated cancer, gelatinous carcinoma, adenoscirrhous with nondifferentiated scirrhous carcinoma, etc. An interesting fact is that the general trend of predominance of carcinoma of almost all histologic forms in males keeps on being valid. It is logical to expect that adenocarcinoma will keep on being the most common histologic form of pancreas cancer in the future.

Adenocarcinoma↗

PubMed1979

[Current status in transplantation of the endocrine pancreas in the treatment of diabetes mellitus 2. Transplantation of fetal pancreas].

The latest findings support hypotheses that diabetes complications are secondary to metabolic control which current insulin therapy is unable to render constant. Surgical attempts to transplant the pancreas and Langerhans islets in the treatment of diabetes mellitus are reviewed and special attention paid to the use of the foetal pancreas which has proved particularly suitable in preventing microangiopathic complication. Comments are based on a careful review of the literature, made in the light of personal experience.

Animals↗

PubMed1989

Contribution of partial pancreatectomy, systemic hormone delivery, and duct obliteration to glucose regulation in canine pancreas. Importance in pancreas transplantation.

Our aim was to isolate and determine the contribution of partial pancreatectomy, systemic delivery of pancreatic hormones, and duct obliteration to glucose regulation after segmental pancreas transplantation in dogs. Fasting, postprandial, and intravenous glucose-stimulated glucose, insulin, glucagon, pancreatic polypeptide (PP), and cholecystokinin (CCK) and intravenous bombesin-stimulated PP levels were studied in beagles at three successive intervals in a crossover design. The first was 6 wk after partial (approximately 70%) pancreatectomy with intact regular enteric exocrine drainage from the duodenal pancreatic remnant, the next was 2 wk after venous transposition with systemic delivery of pancreatic hormones, and the third was 6 wk after in situ duct obliteration of the remnant. With partial pancreatectomy, K values were modestly diminished (30%), and a concomitant reduction of second-phase intravenous glucose-stimulated insulin release was observed. Other parameters were not significantly affected. Venous transposition doubled peripheral plasma levels of insulin under all conditions. Fasting glucose, PP, and CCK levels decreased slightly. Other parameters were not affected. Duct obliteration of the systemic draining pancreatic remnants seriously impaired glucose sensitivity, resulting in a 50% reduction of K values and fasting and sustained postprandial hyperglycemia (approximately 8 mM) and a 70-50% reduction (acute and overall responses, respectively) of intravenous glucose-stimulated insulin. Fasting hormone and postprandial insulin, glucagon, and CCK levels were not affected. The postprandial PP response was severely reduced, and bombesin-stimulated PP release was abolished by duct obliteration. We conclude that histological changes associated with duct obliteration are the major determinants of glucose regulation in segmental pancreas transplantation.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1996

Expression of cathepsin E in pancreas: a possible tumor marker for pancreas, a preliminary report.

Ductal cancers of the pancreas frequently express markers of gastrointestinal epithelial cells. Cathepsin E (CTSE) is a non-secretory, intracellular, but non-lysosomal proteinase found in the highest concentration in the superficial epithelial cells of the stomach. The aims of our study were to examine the expression of CTSE in the pancreas, to establish an assay system of CTSE and to evaluate the diagnostic usefulness of CTSE in the pancreatic juice. Eleven patients with pancreatic ductal adenocarcinoma, 10 with mucin-producing adenoma, 3 with intraductal papillary hyperplasia and 43 with chronic pancreatitis were examined. Surgically resected pancreatic tissues were subjected to immunohistochemistry for CTSE. Pancreatic juice was collected from the patients and subjected to sandwich ELISA and Western analysis for detecting CTSE. Positive staining for CTSE was observed in pancreatic ductal adenocarcinoma by immunohistochemistry. CTSE was also expressed in mucin-producing adenoma, intraductal papillary hyperplasia and mucinous hyperplasia. CTSE in the pancreatic juice was present in 8 of 11 patients with pancreatic ductal adenocarcinoma, 5 of 10 patients with mucin-producing tumor, 1 of 3 patients with intraductal papillary hyperplasia and 4 of 43 patients with chronic pancreatitis. The detection frequency of CTSE in the pancreatic juice was significantly higher in the patients with pancreatic ductal adenocarcinoma than in the patients with chronic pancreatitis. Our findings suggest that the expression of CTSE is associated with the pathogenesis of pancreatic ductal adenocarcinoma, that CTSE in the pancreatic juice seems to be a useful marker for a definitive diagnosis and that CTSE may be expressed at a relatively early stage of multistep carcinogenesis in pancreatic lesions.

Adult↗

PubMed1991

Coxsackie virus B4 infection of the mouse pancreas: I. Detection of virus-specific RNA in the pancreas by in situ hybridisation.

The pathology of Coxsackie virus B4 (CVB4) infection in a murine model was investigated by in situ hybridisation using a biotinylated cDNA probe derived from CVB4. During the acute phase of infection virus RNA sequences were detected in the exocrine pancreas of 60% of mice infected with a pancreotropic variant of CVB4. A positive hybridisation signal was observed in other organs in some animals including the heart and liver of 1 mouse 28 days after infection. The cellular distribution of virus RNA sequences corresponded well with the histological findings in most tissues. Possible causes for failure of hybridisation in some infected pancreases are discussed in conjunction with potential application of the technique in human pancreas biopsy samples.

Animals↗

PubMed2004

Coexistence of annular pancreas with carcinoma in the dorsal part of pancreas divisum: diagnostic value of magnetic resonance cholangiopancreatography.

We report on the incidental observation of a pancreas divisum coexistent with an annular pancreas in a 88-year-old woman presenting with jaundice due to a pancreatic carcinoma. This case report discusses the embryologic hypotheses underlying this peculiar association, highlights the capacities of imaging techniques to depict them, and enhances the performance of magnetic resonance imaging.

Aged↗

PubMed1978

Computed tomography of the pancreas: the use of intravenous contast to define the dorsal surface of the pancreas.

After a non-selective review of 80 abdominal CT examinations, it was found that the use of intravenous contrast markedly improves the recognition of the superior mesenteric vein and the splenic vein. These veins lie adjacent to the posterior surface of the pancreas. When the pancreas is poorly seen due to inadequate retroperitoneal fat, when pancreatic size is borderline, or when pancreatic ductal obstruction is suspected on scans prior to intravenous contrast administration, the use of contrast may resolve the uncertainty.

Abdominal Neoplasms↗

PubMed2004

Echocardiographic evaluation in type 1 diabetic patients on waiting list for isolated pancreas or kidney-pancreas transplantation.

Type 1 diabetic patients may display abnormalities of left ventricular geometry and systolic and diastolic function. Patients on the waiting list for solitary pancreas or kidney-pancreas transplantation were evaluated by Doppler echocardiography to assess left ventricular geometry and systolic and diastolic function, and correlate these parameters with clinical characteristics. We evaluated 78 patients including 45 men with an overall mean age of 39.5 +/- 7.2 years and a disease duration of 24 +/- 9.8 years. Among these 78 patients, 13 showed isolated retinopathy, 9 isolated arterial hypertension, 45 concomitant retinopathy and hypertension and overt nephropathy, while 11 were free of complications. The results of our study showed an increased left ventricular mass and abnormal diastolic function among patients with simultaneous target organ complications and with hypertension, as has been reported in many previous studies. In contrast study patients with no complications showed normal left ventricular structure and function. This finding conflicts with data from several reports in the medical literature in which diastolic impairment was present in type 1 diabetic patients at an early stage of disease and with no evident microvascular and macrovascular complications.

Adult↗