• Malignant insulinoma.

• Papillary and cystic insulinoma of the pancreas.

• Deletion of chromosome 1, but not mutation of MEN-1, predicts prognosis in sporadic pancreatic endocrine tumors.

• Overexpression of the Sm-like proto-oncogene in primary and metastatic pancreatic endocrine tumors.

• Localization of insulinomas to regions of the pancreas by intra-arterial stimulation with calcium.

• Insulinoma: cost-effective care in patients with a rare disease.

• Forty-eight-hour fast: the diagnostic test for insulinoma.

• Brittle nails and dyspareunia as first clues to recurrences of malignant glucagonoma.

• Helical CT of islet cell tumors of the pancreas: typical and atypical manifestations.

• Surgical experience with functioning pancreatic neuroendocrine tumors.

• [Non-functional islet-cell tumor: analysis of 237 cases]

1
UI - 12126364
AU - Saravu K; Sheshadri S; Sean TG
TI - Malignant insulinoma.
SO - J Assoc Physicians India 2002 Jul;50():983-4
AD - Department of Medicine, Kasturba Medical College, Manipal.

2
UI - 12010374
AU - Pareja-Megia MJ; Rios-Martin JJ; Garcia-Escudero A; Gonzalez-Campora R
TI - Papillary and cystic insulinoma of the pancreas.
SO - Histopathology 2002 May;40(5):488-90

3
UI - 11960210
AU - Guo SS; Wu AY; Sawicki MP
TI - Deletion of chromosome 1, but not mutation of MEN-1, predicts prognosis in sporadic pancreatic endocrine tumors.
SO - World J Surg 2002 Jul;26(7):843-7
AD - Department of Surgery, West Los Angeles VA Medical Center and the UCLA School of Medicine, Los Angeles, CA 90073, USA.
Pancreatic endocrine tumors (PETs) may be sporadic or inherited in the multiple endocrine neoplasia type 1 (MEN-1) syndrome. The inherited form is caused by mutations of the MEN-1 gene, which functions as a tumor suppressor gene and maps to chromosome 11q13. These tumors tend to have a better prognosis than their sporadic counterparts, which often have mutations of the MEN-1 gene. Previous molecular analyses of sporadic PETs suggest a high frequency of loss of heterozygosity (LOH) at chromosome 1 as well as mutation of MEN-1. In this study we correlate abnormalities of MEN-1 and chromosome 1 LOH with the biological behavior of sporadic PETs. Loss of heterozygosity for markers at chromosome 11q13 and mutation of MEN-1 were equally frequent in tumors with or without liver metastases. Mutation of MEN-1 is more frequent in gastrinomas than in non-gastrinomas. Loss of heterozygosity for markers on chromosome 1 is more frequent in PETs with liver metastases. These results suggest a molecular tumor model in which there is a dichotomy in the development of benign and malignant PETs.

4
UI - 12110768
AU - Gumbs AA; Bassi C; Moore PS; Falconi M; Frigerio I; Baron A; Piemonti L;
TI - Modlin I; Scarpa A Overexpression of the Sm-like proto-oncogene in primary and metastatic pancreatic endocrine tumors.
SO - JOP 2002 Jul;3(4):109-15
AD - Department of Surgical and Gastroenterological Sciences, University of Verona. Verona, Italy.
CONTEXT: The cancer associated Sm-like proto-oncogene mRNA has been found to be overexpressed in the majority of pancreatic adenocarcinomas and is necessary for the transformed phenotype in pancreatic cancer cell lines. However, expression levels have not been examined in other types of pancreatic neoplasms, such as pancreatic endocrine tumors. SETTING: Fifteen primary pancreatic endocrine tumors, including five insulinomas and 10 non-functioning tumors, along with seven hepatic metastatic pancreatic endocrine tumors. MAIN OUTCOME MEASURES: Quantitative expression levels of cancer associated Sm-like mRNA were measured by real-time PCR. Overexpression was defined as a two-fold or greater value when compared to the expression levels found in normal pancreatic islet cells obtained from healthy donors. RESULTS: In primary tumors, four of the 10 non-functioning pancreatic endocrine tumors were found to overexpress cancer associated Sm-like mRNA (40%). Three of the five (60%) insulinomas also overexpressed cancer associated Sm-like mRNA. In total, cancer associated Sm-like mRNA was overexpressed in seven of 15 primary tumors (47%) and in the majority (71%, 5 of 7) of the hepatic metastases. CONCLUSIONS: Our results indicate that the cancer associated Sm-like mRNA gene may also play a role in the tumorigenesis of pancreatic endocrine tumors.

5
UI - 7611592
AU - Doppman JL; Chang R; Fraker DL; Norton JA; Alexander HR; Miller DL;
TI - Collier E; Skarulis MC; Gorden P Localization of insulinomas to regions of the pancreas by intra-arterial stimulation with calcium.
SO - Ann Intern Med 1995 Aug 15;123(4):269-73
AD - Diagnostic Radiology Department, Clinical Center, National Institutes of Health, Bethesda, MD 20892-1182, USA.
OBJECTIVE: To determine the sensitivity of calcium injected into pancreatic arteries in localizing insulin-secreting tumors to regions of the pancreas. DESIGN AND PATIENTS: To stimulate the release of insulin, 25 patients with surgically proven insulinomas (average diameter, 15 mm) had calcium gluconate (0.025 mEq Ca++/kg body weight) injected before surgery into the arteries supplying the pancreatic head (gastroduodenal and superior mesenteric arteries) and the body and tail (splenic artery) of the pancreas. SETTING: Tertiary referral hospital. MEASUREMENTS: Insulin levels were measured in samples taken from the right and left hepatic veins before and 30, 60, and 120 seconds after calcium injection. A twofold increase in insulin level in the sample taken from the right hepatic vein 30 or 60 seconds after injection localized the insulinoma to the segment of the pancreas supplied by the selectively injected artery. Localization done using calcium stimulation was compared with localization done using transcutaneous ultrasonography (n = 22), computed tomography (n = 23), magnetic resonance imaging (n = 21), arteriography (n = 25), and portal venous sampling (n = 9). RESULTS: Calcium stimulation localized 22 of 25 insulinomas (sensitivity, 88% [95% CI, 68% to 97%]) to the correct region of the pancreas. The sensitivities of the other imaging methods were 9% for ultrasonography (CI, 1% to 23%), 17% for computed tomography (CI, 5% to 39%), 43% for magnetic resonance imaging (CI, 22% to 66%), 36% for arteriography (CI, 18% to 57%), and 67% for portal venous sampling (CI, 30% to 93%). Calcium stimulation added only a few minutes to the time needed for pancreatic arteriography and caused no morbid conditions. CONCLUSION: Intra-arterial calcium stimulation with right hepatic vein sampling for insulin gradients is the most sensitive preoperative test for localizing insulinomas.

6
UI - 7611598
AU - Axelrod L
TI - Insulinoma: cost-effective care in patients with a rare disease.
SO - Ann Intern Med 1995 Aug 15;123(4):311-2

7
UI - 10999812
AU - Hirshberg B; Livi A; Bartlett DL; Libutti SK; Alexander HR; Doppman JL;
TI - Skarulis MC; Gorden P Forty-eight-hour fast: the diagnostic test for insulinoma.
SO - J Clin Endocrinol Metab 2000 Sep;85(9):3222-6
AD - Division of Intramural Research, National Institute of Diabetes, Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA.
Insulinoma causes fasting hypoglycemia due to inappropriate insulin secretion. Its diagnosis is based on demonstrating Whipple's triad during a supervised 72-h fast. For 75 yr, the 72-h fast has been the cornerstone for the diagnosis; however, it has never been critically assessed using newer assays for insulin, C peptide, and proinsulin. Thus, the aim of the current study is to assess the need for a full 72-h fast for the diagnosis of insulinoma. Patients with suspected hypoglycemia with documented glucose concentrations below 45 mg/dL were admitted to the NIH. Data obtained during the supervised fast of patients with pathologically proven insulinoma over a 30-yr period (1970-2000) were reviewed. We identified 127 patients with insulinoma. The average age of patients was 42.7 +/- 15.9 yr, with a predominance of females (62%). 107 patients had a benign tumor, 20 had malignant insulinoma, and 15 patients had multiple endocrine neoplasia type 1. The fast was terminated due to hypoglycemia in 44 patients (42.5%) by 12 h, 85 patients (66.9%) by 24 h, and 120 (94.5%) by 48 h. Seven patients fasted beyond 48 h despite subtle neuroglycopenic symptoms and glucose and insulin concentrations diagnostic of insulinoma. Immunoreactive proinsulin was elevated at the beginning of the fast in 90% of 42 patients. Proinsulin in noninsulinoma, in contrast to insulinoma, patients is usually suppressible; therefore, samples taken in the suppressed state have the greatest diagnostic value. We conclude that with the current available insulin and proinsulin assays, the diagnosis of insulinoma can be made within 48 h. Thus, the 48-h fast should replace the 72-h fast in textbooks and hospital protocols as the new diagnostic standard.

8
UI - 12072081
AU - Chao SC; Lee JY
TI - Brittle nails and dyspareunia as first clues to recurrences of malignant glucagonoma.
SO - Br J Dermatol 2002 Jun;146(6):1071-4
AD - Department of Dermatology, National Cheng-Kung University Hospital, 138 Sheng-Li Road, 704 Tainan, Taiwan.
Glucagonoma syndrome is a paraneoplastic syndrome in which the occurrence and resolution of the characteristic necrolytic migratory erythema lesions parallel the course of the underlying glucagonoma. Nail abnormalities and dyspareunia are rarely reported in this syndrome. We describe a case of glucagonoma syndrome in which recurrent brittle nails and dyspareunia gave the patient the first clues of the recurrence of glucagonoma. It is possible that the significance of onychoschizia and dyspareunia has been overlooked in glucagonoma syndrome because patients might not report these problems to their doctors. Our case illustrates the importance of examining the nail and genital mucosa in patients with glucagonoma syndrome and including this syndrome in the differential diagnosis of onychoschizia and dyspareunia.

9
UI - 12185053
AU - Sheth S; Hruban RK; Fishman EK
TI - Helical CT of islet cell tumors of the pancreas: typical and atypical manifestations.
SO - AJR Am J Roentgenol 2002 Sep;179(3):725-30
AD - Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins University, 600 N. Wolfe St., Nelson B176D, Baltimore, MD 21287, USA.

10
UI - 12206598
AU - Matthews BD; Smith TI; Kercher KW; Holder WD Jr; Heniford BT
TI - Surgical experience with functioning pancreatic neuroendocrine tumors.
SO - Am Surg 2002 Aug;68(8):660-5; discussion 665-6
AD - Department of General Surgery, Carolinas Medical Center, Charlotte, North Carolina 28203, USA.
Pancreatic islet-cell tumors (ICTs) are rare malignancies usually recognized by specific clinical endocrinopathies. The purpose of this study is to evaluate our surgical experience with functioning pancreatic ICT in an academic referral center. Twenty patients (male:female 12:8) with a mean age of 53 years (range 26-82) underwent surgery for a functioning pancreatic ICT [gastrinoma (eight), multiple endocrine neoplasia (three), insulinoma (seven), glucagonoma (four), and VI-Poma Signs and symptoms of hormonal excess were present in 95 per cent (19 of 20). One patient (glucagonoma) presented with obstructive jaundice and mild glucose intolerance. Elevated peptide levels were detected preoperatively in 65 per cent, including all patients with an insulinoma. Curative resections were attempted in 80 per cent including three procedures for insulinoma. Palliative procedures were performed in 20 per cent--all gastrinomas. One patient with an insulinoma had diffuse nesidioblastosis. Three patients (with gastrinoma, insulinoma, and glucagonoma) had lymph node-positive disease and three patients with gastrinoma had liver metastasis. The overall 30-day morbidity rate was 30 per cent and mortality rate 0 per cent. Symptomatic improvement was achieved in 90 per cent at a mean follow-up of 44 months. Two patients developed diabetes after a subtotal and a total pancreatectomy, respectively. Sixty-three per cent of patients who underwent an attempted curative resection are alive at a mean follow-up of 47 months (range 3-231) and all patients who underwent a palliative procedure are alive at a mean follow-up of 31 months (range 27-36). Functioning pancreatic ICTs are fascinating tumors that produce distinct clinical syndromes. Symptomatic improvement is accomplished in the majority of patients after surgery and short-term palliation is achieved in patients with nonresectable disease.

11
UI - 11953201
AU - Yang Z; Zhao P; Liu Z; Tang W; Zhong S
TI - [Non-functional islet-cell tumor: analysis of 237 cases]
SO - Zhonghua Yi Xue Za Zhi 2002 Mar 25;82(6):376-8
AD - Department of General Surgery, Peking Union Medical College Hospital, Beijing 100730, China.
OBJECTIVE: To summarize the clinical aspects of nonfunctional islet-cell tumor (NIT) reported in Chinese periodicals. METHODS: Articles in Chinese on NIT were screened from the Chinese Bio-Medical Database (1981.1 - 1999.10). Data of epidemiology, clinical manifestations, diagnosis, defferential diagnosis, and treatment of NIT were analyzed. RESULTS: 60 articles and 237 cases of NIT were selected. The female to male ratio was 2.9:1. Abdominal mass was the most common clinical symptom. It was difficult for the pre-operative diagnosis of NIT and differentiation from pancreatic tumor or retroperitoneal mass. The malignant rate of NIT was 35%. The five-year survival rate of malignant NIT was 53.1%. CONCLUSION: NIT is rare. It occurs more often in female than in male. The preoperative diagnostic rate is rather low. The prognosis of malignant NIT is favorable. Active treatment is strongly recommended.

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