Pancreatic Islet Cell Adenoma Research Articles

Causes of Mortality in a Population of Marine-Foraging River Otters (Lontra canadensis).

Retrospective analysis of diagnostic findings from 30 marine-foraging river otter (Lontra canadensis) carcasses opportunistically acquired between 2003 and 2013 revealed trauma as the most common cause of mortality (47%). Within this focal population, causes of trauma included vehicular, gunshot, and one case of suspect intraspecific aggression. Other causes of death included idiopathic (20%), infectious (13%), metabolic (10%), nutritional (7%), and neoplasia (3%). One case of neoplasia, a pancreatic islet cell adenoma, was identified in a 12-yr-old female. In six animals, diffuse renal interstitial fibrosis and multifocal glomerulosclerosis of unknown clinical significance were noted.

Transition of Historical Control Data for High Incidence Tumors in F344 Rats

Historical control data of tumor incidence were collected from the control groups (215 animals of each sex) in four recent carcinogenicity studies that were started between 2005 to 2009 (terminally sacrificed between 2007 and 2011) at BoZo Research Center Inc. (Gotemba, Shizuoka, Japan) using Fischer 344 rats (F344/DuCrlCrlj). These data were compared to the previous historical control data (from 1990 to 2004, previously reported) in the same facility. In the results, the incidence of C-cell adenoma in the thyroid tended to increase in both sexes in recent years (30.8% for males and 24.4% for females in 2005-2009) as compared with the previous data (17.4% and 20.1% for males and 11.5% and 11.8% for females in 1990–1999 and 2000–2004, respectively). In addition, the incidences of pancreatic islet cell adenoma in males and uterine adenocarcinoma tended to increase from around 2000 and remained high in recent years (incidences of islet cell adenoma in males of 10.5%, 17.1% and 20.5% in 1990–1999, 2000–2004 and 2005–2009; incidences of uterine adenocarcinoma of 3.3%, 12.0% and 13.5% in 1990–1999, 2000–2004 and 2005–2009, respectively). There was no apparent difference in the incidence of other tumors.

Historical control data of neoplastic lesions in the Wistar Hannover Rat among eight 2-year carcinogenicity studies

Incidences of neoplastic lesions were evaluated in untreated Hannover Wistar Rats RjHan: WI (470 males and 470 females) used as control animals in eight carcinogenicity studies. All these studies were performed in a similar environment either for the in vivo and the postmortem evaluation. The major neoplastic lesions were found in the endocrine, integumentary and reproductive systems. Pituitary adenoma was the most frequent neoplasm and occurred in 33.9% of the males and 54.6% of the female rats. The other most frequent tumors in males were thyroid C-cell adenoma (8.6%), pancreatic islet cell adenoma (8.1%), subcutaneous fibrosarcoma (6.6%), subcutaneous fibroma (4.7%), benign pheochromocytoma (3.4%), and cutaneous keratoacanthoma (3.4%). In females, the other highest incidences were mammary fibroadenoma (29%), uterine endometrial stromal polyp (18.1%), mammary adenocarcinoma (14.2%), mammary fibroadenoma with atypia (13.7%), thyroid C-cell adenoma (7.5%), benign thymoma (3.7%), and subcutaneous fibrosarcoma (3.6%). All these data were compared to previously published historical control data. This retrospective analysis was undergone in order to illustrate the result of a stable organization which guarantees a robust historical data base for neoplastic and non neoplastic findings.

Toxicity and carcinogenicity of androstenedione in F344/N rats and B6C3F1 mice

Androstenedione was marketed as a dietary supplement to increase muscle mass during training. Due to concern over long-term use, the NTP evaluated the subchronic and chronic toxicity and carcinogenicity of androstenedione in male and female F344/N rats and B6C3F1 mice. In subchronic studies, dose limiting effects were not observed. A chronic (2-year) exposure by gavage at 10, 20, or 50mg/kg in rats and male mice, and 2, 10, or 50mg/kg in female mice (50mg/kg, maximum feasible dose) was conducted. Increased incidences of lung alveolar/bronchiolar adenoma and carcinoma occurred in the 20mg/kg male rats and increases in mononuclear cell leukemia occurred in the 20 and 50mg/kg female rats, which may have been related to androstenedione administration. In male and female mice, androstenedione was carcinogenic based upon a significant increase in hepatocellular tumors. A marginal increase in pancreatic islet cell adenomas in male (50mg/kg) and female (2, 10, 50mg/kg) mice was considered to be related to androstenedione administration. Interestingly, incidences of male rat Leydig cell adenomas and female rat mammary gland fibroadenomas decreased. In conclusion, androstenedione was determined to be carcinogenic in male and female mice, and may have been carcinogenic in rats.

Toxicity and carcinogenicity studies of methylene blue trihydrate in F344N rats and B6C3F1 mice

Methylene blue trihydrate has a variety of biomedical and biologically therapeutic applications. Groups of 50 male and 50 female rats and mice were administered methylene blue trihydrate in 0.5% aqueous methylcellulose solution by gavage at doses of 0, 5, 25, or 50 mg/kg bw/day (rats) or 0, 2.5, 12.5, and 25 mg/kg bw/day (mice), 5 days per week for 2 years. In rats survival of all dosed groups was similar to that of the vehicle controls, whereas mice exhibited a dose-dependent increase in survival. Rats receiving 25 and 50 mg/kg bw/day and mice receiving 25 mg/kg bw/day developed mild anemia. The incidences of pancreatic islet cell adenoma and adenoma or carcinoma (combined) were increased in all dosed groups of male rats, but increases were statistically significant in 25 mg/kg bw/day males only and the dose–response was non-linear. There was a corresponding increase in the incidence of pancreatic islet cell hyperplasia but statistically significant only in the 50 mg/kg bw/day male rats. There were no significant increases in neoplastic transformation observed in the mice; however, positive trends were noted for adenoma or carcinoma (combined) of the small intestine and malignant lymphoma.

Spontaneous pathology of the baboon endocrine system

Study of endocrine pathology in animal models is critical to understanding endocrine pathology in humans. We evaluated 434 endocrine-related diagnoses from 4619 baboon necropsies, established the incidence of spontaneous endocrine pathology, and analyzed the clinical and biochemical data associated with the individual cases. The most common diagnoses in descending order, were pancreatic islet cell amyloidosis (n = 259), ovarian cysts (n = 50), pituitary adenoma (n = 37), pancreatic islet cell adenoma (n = 20), granulosa cell tumor (n = 15), thyroid adenoma (n = 11), adrenal hyperplasia (n = 10), thyroid carcinoma (n = 8), and pheochromocytoma (n = 6). The incidence of pancreatic islet cell amyloidosis progressively increased with age. Pheochromocytomas were associated with renal and heart failure. The incidence of pancreatic islet cell amyloidosis and adrenal pathology was similar to humans; the incidence of pituitary adenoma and thyroid pathology was lower than in humans. Endocrine disease in baboons is common and shares clinical and biochemical characteristics with endocrine disease in humans.

Two cases of pancreatic neoplasia in British ferrets (Mustela putorius furo)

Two six-year-old male neutered polecat ferrets (Mustela putorius furo) were presented for the investigation of acute collapse or periodic weakness and weight loss. While blood biochemistry revealed hypoglycaemia in both cases, diagnosis of an insulin-secreting neoplasia was confirmed by exploratory surgery in one case and supported by the use of an insulin assay in the other. Subsequent histopathological examination showed the former to be a pancreatic islet cell carcinoma and the latter to be a pancreatic islet cell adenoma. While neoplasia of the pancreas commonly affects ferrets in the USA, there appears to be only one previous report from the UK.

Spontaneous Neoplasms in Control Wistar Rats: A Comparison of Reviews

Spontaneous neoplasms in 930 control Wistar rats from five carcinogenicity bioassays conducted between 1990 and 1995 were reviewed and compared with review findings in studies between 1980 and 1990. Mean survival at 104 weeks was 55% for males and 60% for females, similar to that of the previous review. A total of 1599 neoplasms was diagnosed in 361 (78%) male and 415 (89%) female rats; 1293 (81%) of these were benign and 306 (19%) were malignant (11% with metastases). Sixty-eight percent of all neoplasms were in endocrine and integumentary systems, similar to 74% seen in the previous review. Most common neoplasms (affecting >7% of either sex) were pituitary adenoma (34% of males, 50% of females), benign adrenal pheochromocytoma (10% of males, 1% of females), thyroid C cell adenoma (6% of males, 8% of females), mammary fibroadenoma (3% of males, 36% of females), keratoacanthoma (11% of males, 0.6% of females), testicular interstitial cell tumor (11% of males), uterine stromal polyp (16% of females), pancreatic acinar cell adenoma (13% of males, 0.6% of females), and benign thymoma (3% of males, 8% of females). Seventeen neoplasms affecting 2 to 6.9% of either sex included adrenal cortical adenoma, thyroid follicular adenoma, pancreatic islet cell adenoma, pituitary carcinoma, mammary adenoma, mammary adenocarcinoma, fibroma, fibrosarcoma, dermal papilloma, uterine schwannoma, uterine granular cell tumor, pancreatic acinar cell carcinoma, hepatocellular adenoma, lymphoma, granular cell meningioma, renal mesenchymal tumor, and hemangiosarcoma. Remaining neoplasms occurred in fewer than 2% of animals. Mean tumor incidence did not differ significantly between our two reviews. Ratios of benign to malignant neoplasms were similar in both reviews and percentages of survival at 104 weeks were similar. Between the two reviews, greater than threefold increase in frequency of some neoplasms occurred only in males and included keratoacanthomas, pancreatic acinar cell adenomas/carcinomas, and astrocytomas. Frequencies of remaining neoplasms were within twofold or within 10% of previous frequencies. Some neoplasms diagnosed in this review but not in the previous review included cardiac schwannoma, pilomatrixoma, parathyroid adenoma, and prostatic adenoma but incidence was approximately 1% any one tumor. Based on these reviews, Wistar rats appear to have a predilection to pituitary neoplasms and mammary fibroadenomas (females).

Localisation of a gene causing endocrine neoplasia to a 4 cM region on chromosome 1p35-p36.

The development of some endocrine tumours, such as medullary thyroid carcinomas, phaeochromocytomas, anterior pituitary adenomas, and parathyroid adenomas involve a putative tumour suppressor gene located on chromosome 1p32-pter, a region...

Spontaneous Neoplasms in Control Wistar Rats

Spontaneous Neoplasms in Control Wistar Rats. Walsh, K. M., and Poteracki, J. (1994). Fundam. Appl. Toxicol. 22, 65-72.Neoplastic data on 1370 control Wistar rats from 10 carcinogenicity bioassays done between 1980 and 1990 were reviewed. Mean percentage survival at 104 weeks was 58% for males and 59% for females. A total of 1857 neoplasms were diagnosed in 466 (68%) male and 582 (85%) female rats; 1390 were benign and 467 were malignant (12% with metastasis). Seventy-four percent of all neoplasms were in endocrine and reproductive systems. Most common neoplasms (affecting more than 7% of either sex) were pituitary adenoma (27.7% males; 55.0% females), mammary fibroadenoma (1.0% males; 25.3% females), mammary adenocarcinoma (1.0% males; 13.1% females), adrenal cortical adenoma (8.3% males; 9.3% females), and endometrial stromal polyp (9.6% females). Fourteen neoplasms affecting 2 to 6% of either sex included adrenal pheochromocytoma, thyroid C cell adenoma, thyroid follicular adenoma, pancreatic islet cell adenoma, lymphoma, histiocytic sarcoma, thymoma, hepatic adenoma, pancreatic acinar adenoma, mammary adenoma, dermal fibroma, astrocytoma, testicular interstitial cell tumor, and ovarian granulosa cell tumor. Remaining neoplasms were seen in less than 2% of animals.

Spontaneous neoplasms in aged Sprague-Dawley rats.

Incidence of neoplastic lesions in untreated Sprague-Dawley rats (1340 males and 1329 females) used as controls in 17 carcinogenicity studies are tabulated and evaluated. In male rats, the most common neoplasms were benign pheochromocytomas and keratoacanthomas (4.0% in each case) followed by pancreatic islet cell adenomas (3.7%), thyroid parafollicular cell adenomas (3.6%), fibromas and squamous cell papillomas of the skin and hepatocellular adenomas (2.0% in each), malignant lymphoma lymphocytic (1.9%), histiocytic sarcomas (1.4%), and adrenal cortical adenomas (1.2%). In female rats, the most common neoplasms were of mammary gland origin (31.3%: fibroadenoma 19.0%, adenocarcinomas 8.8%, and adenomas 3.5%) followed by thyroid parafollicular cell adenomas (2.9%), uterine endometrial stromal polyps (2.6%), adrenal cortical adenomas (1.9%), malignant lymphoma lymphocytic (1.6%), fibromas in the skin (1.3%), and pancreatic islet cell adenoma (1.1%). Metastases were observed from pheochromocytomas, hepatocellular carcinomas, nephroblastomas, renal pelvis transitional cell carcinoma, interstitial cell tumor and seminoma of the testes, Zymbal's gland adenocarcinomas, and mammary adenocarcinomas.

Neoplasms and Related Proliferative Lesions in Control Sprague-Dawley Rats from Carcinogenicity Studies. Historical Data and Diagnostic Considerations

Historical data are presented for neoplasms and related proliferative lesions from 1,170 Sprague-Dawley rats that served as controls in 9 carcinogenicity (2 year) studies conducted in the Safety Evaluation Facility of Ciba-Geigy Corporation, Summit, New Jersey. The most common neoplasm was pituitary adenoma, which occurred in 62.2% of the male and 84.7% of the female rats. Incidences of other neoplasms that occurred in more than 6.0% of the rats were, for males, benign pheochromocytoma (19.0%), cutaneous keratoacanthoma (7.9%), pancreatic islet cell adenoma (7.5%), benign testicular interstitial cell tumor (6.5%), and thyroid C-cell adenoma (6.5%). For females these incidences were mammary fibroadenoma (31.3%), mammary adenocarcinoma (16.8%), and mammary adenoma (6.5%). Focal cortical hypertrophy/cystic degeneration of the adrenal, a focal nonneoplastic lesion of zona fasciculata cells that often degenerate into large cysts, was present in 23.4% of all male and 82.7% of all female rats. Criteria for the differential diagnoses of selected neoplasms and related lesions are presented.

Spontaneous neoplasms in aged control Fischer 344 rats

Neoplastic lesions in untreated F-344 rats (740 males and 740 females) used as controls in carcinogenicity studies were evaluated and tabulated. The incidence of spontaneous tumors was 84.3% in the males and 76.2% in the females. In males, the most common neoplasms were testicular interstitial cell tumors (79.5%) followed by mononuclear cell leukemia/lymphomas (30.5%), pituitary adenomas (20.5%), pancreatic islet cell adenomas (6.5%), thyroid c-cell adenomas (5.7%), pheochromocytomas (5.7%), skin fibromas (3.2%), keratoacanthomas (1.9%), and thyroid follicular cell adenomas (1.9%). In females, the most common neoplasms were pituitary adenomas (30.3%) followed by mononuclear cell leukemia/lymphomas (20.5%), endometrial polyps (14.1%), mammary fibroadenomas (11.1%), thyroid c-cell adenomas (5.1%), mammary adenomas (1.9%), skin fibromas (1.1%), and clitoral carcinomas (1.1%). A variety of less common neoplasms were also observed in various other organs.

Preventive and Enhancing Effects of Retinoids on the Development of Naturally Occurring Tumors of Skin, Prostate Gland, and Endocrine Pancreas in Aged Male ACI/segHapBR Rats<xref ref-type="fn" rid="FN2">2</xref>

The effects of dietary retinoids on the development of naturally occurring tumors in retired breeder male ACI/segHapBR rats were investigated. Groups of rats (21-25 mo of age, an age when early neoplasms first appear and tumor incidences are generally low) were fed diets containing 1 of 3 retinoids--all-trans-N-4-(4-hydroxyphenyl)retinamide (4-HPR), 783 mg/kg diet; all-trans-N-(4-pivaloyloxyphenyl)retinamide (4-PPR), 951 mg/kg; or all-trans-4-N-(2-hydroxyethyl)retinamide (2-HER), 687 mg/kg--or control diet for up to 54 weeks (average, 33 wk). Rats were maintained until less than 20% remained and the experiment was terminated. Contributing causes of death were determined, and a complete necropsy was performed for each rat. There was no difference between the retinoid-treated rats and control rats in the average age at death (30-31 mo) or in the average experimental survival time (29-35 wk), in the proportions of tumor-bearing rats (95.6-100%), or in the average number of organs with tumor per rat (2.1-2.5). The incidences of pancreatic islet cell adenoma and skin tumors were significantly different between control and some retinoid-treated groups. 4-PPR and 2-HER significantly enhanced pancreatic islet cell adenoma yields (P less than .025 and 0.05, respectively) whereas 4-HPR significantly inhibited epithelial and connective tissue skin tumor yields (P less than .025). Incidences of skin and prostate tumors were lower than in controls, but not significantly, in rats receiving 4-PPR and 2-HER. Most of the islet cell adenomas were shown, by avidin-biotin-peroxidase complex immunocytochemistry, to be insulinomas. 4-HPR would seem to be the most effective retinoid in the group, inasmuch as it prevented skin tumor development, may have slightly decreased the incidence of prostate tumors, and did not enhance islet cell tumor incidence.

Systemic Fibrosclerosis with Intracranial Involvement and Pancreatic Islet Cell Adenoma

Systemic Fibrosclerosis with Intracranial Involvement and Pancreatic Islet Cell Adenoma

Mammary Tumors, Hepatocellular Carcinomas, and Pancreatic Islet Changes in C3H-A vy Mice 2

Studies of tumor incidence and assorted lesions found in 187 C3H-Avy mice throughout their natural life-spans revealed the following: Hepatocellular carcinomas occurred in 54.3% of males, mammary carcinomas in 95% of females, pancreatic islet cell adenomas in 9.4% of males and in no females, and pancreatic islet cell hyperplasia in 41% of males and 23% of fefemales. Islet cell hyperplasia and adenomas appeared to consist predominantly of alpha and delta cells. Multiple tumors, or hyperplasia, or both, of a single site or of multiple sites occurred as frequently in males as they did in females--49.6% and 51.7% respectively. The most frequent neoplasms were hepatocellular carcinomas and islet cell tumors or hyperplasia in males (45.7%) and multiple mammary tumors in females (30%). Heretofore unreported tumors found in this strain of mouse were 12 islet cell adenomas, 2 spindle cell tumors of the meninges and olfactory lobes, a squamous cell carcinoma of the nasal turbinates, and a schwannoma of the spermatic cord.

Evidence for secretion of vasoactive intestinal peptide by tumours of pancreas, adrenal medulla, thyroid and lung: support for the unifying APUD concept.

Levels of vasoactive intestinal polypeptide (VIP) were measured by radioimmunoassay in plasma or tissue from thirty-five patients with watery diarrhoea, and in plasma of twenty-five normal controls. Plasma levels were between 0.6 and 11.0 ng/ml in thirty-one of the thirty-three patients in whom it was measured and too low to measure (less than 200 pg/ml) in the other two. Peptide levels were less than 200 pg/ml in twenty-three of the controls, but higher in the remaining two. All tissues from patients were "rich" in VIP (10 ng to 35 microgram per g). The aetiologic diagnoses included pancreatic islet-cell adenoma or adenocarcinoma, islet-cell hyperplasia, bronchogenic carcinoma, pheochromocytoma, ganglioneuroblastoma, medullary thyroid carcinoma, and retroperitoneal histiocytoma. The findings support the conclusions that: (1) VIP is a likely mediator of the water-diarrhoea syndrome; (2) the syndrome may result from a variety of tumours; (3) this or a related peptide hormone may be secreted by these tumours; and (4) these tumours may have a common embryonic origin.

Elevated Plasma and Tissue Levels of Vasoactive Intestinal Polypeptide in the Watery-Diarrhea Syndrome Due to Pancreatic, Bronchogenic and Other Tumors

The actions of the vasoactive intestinal polypeptide make it a potential candidate for mediating certain manifestations of the watery-diarrhea syndrome. Peptide levels were measured by radioimmunoassay in 25 controls and 30 patients with chronic watery diarrhea. Plasma levels were too low to measure (smaller 200 pg per milliliter) in 22 of the controls, averaging 79 plus or minus 64 pg per milliliter (S.D.). Levels were elevated in 26 of 28 plasma samples (5.1 plus or minus 2.5 ng per milliliter), and in each of 13 tissue extracts (5.1 plus or minus 10.9 mug per gram); in all, 28 patients had elevated levels in plasma or tissue or both. Thirteen patients had pancreatic islet-cell adenoma, four islet-cell hyperplasia, five bronchogenic carcinoma, and one each pheochromocytoma and ganglioneuroblastoma. The findings indicate that the peptide is a probable mediator of the watery-diarrhea syndrome, that the syndrome may result from a variety of non-pancreatic tumors, and that this or a related peptide may also be secreted by these tumors.

Somatostatin Inhibition of Insulin and Gastrin Hypersecretion in Pancreatic Islet-Cell Carcinoma

SOMATOSTATIN has been reported to diminish basal insulin levels1 and to inhibit insulin secretion stimulated by glucose,2 arginine,3 glucagon,4 and tolbutamide4 in normal man. These effects of somatostatin administration have not been associated with serious untoward effects. Therefore, it has been suggested5 that somatostatin might be efficacious in suppressing autonomous hypersecretion of insulin by pancreatic islet-cell adenomas or carcinomas. In the following case, somatostatin was indeed found to be effective in suppressing insulin hypersecretion in a woman with metastatic pancreatic islet-cell carcinoma. Somatostatin also reduced elevated serum gastrin levels. Case Report A 54-year-old woman was admitted to the University of . . .

Cytological differentiation of asymptomatic pancreatic islet cell tumours in autopsy material.

In eleven cases thirteen pancreatic islet cell adenomas were found in autopsy material from 1366 adult cases. Ten of the adenomas were solitary, while 3 small adenomas were observed in a single case. Another four possible solitary adenomas were observed, but their identity was uncertain owing to marked fibrosis. All the adenomas contained A-2 (A)-1 cells but no B (B)-1 cells. Nine of them also contained A-1 (D)-1 cells. The majority of cells in the adenomas were A-2 cells or cells which did not stain with any of the techniques used. The 4 possible adenomas contained islet cells (A-1, A-2, B) in different proportions. With one exception the patients with adenomas and possible adenomas were 65 years of age or older, and in some of these cases adenomas or hyperplasias were also found in other endocrine organs. The frequency of gastroduodenal ulcers or scars in the cases with adenoma or possible adenoma did not differ notably from that found in the cases without pancreatic adenomas. Among the cases with pancreatic adenoma and possible adenoma there were 3 patients with maturity onset diabetes mellitus, but otherwise no clinical symptoms of endocrine disturbances were noted.