Support for a postresection prognostic score for pancreatic endocrine tumors.

BACKGROUND: Prognostic scores predicting long-term survival of patients with pancreatic neuroendocrine tumors (PNETs) have been created. The purpose of this study was to validate a prognostic scoring scheme at a single institution. METHODS: We reviewed all resections for PNETs from 1996 to 2004. Prognostic scores based on patient age, tumor grade, and distant metastasis were calculated. Survival was compared with an established postresection prognostic score for PNETs. RESULTS: A total of 34 PNETs were identified. Predicted 5-year survival for prognostic scores of 1, 2, and 3 were 76.7%, 50.9%, and 35.7%, respectively. Final prognostic scores of 1, 2, and 3 were observed in 13 (38%), 18 (53%), and 3 (9%) patients, with observed actual 5-year survivals of 92.3%, 72.2%, and 66.7%, respectively. CONCLUSIONS: PNET prognostic scores were found to be inversely related to survival. PNET postresection prognostic score categories may be useful tools in predicting long-term survival.

Incidence rates of exocrine and endocrine pancreatic cancers in the United States.

Descriptive studies of pancreatic cancer incidence have been sparse particularly in terms of tumor histology and stage. The purpose of this study was to examine the incidence rate trends of exocrine and endocrine pancreatic cancers by demographic and tumor characteristics using data from the Surveillance, Epidemiology, and End Results (SEER) program from 1977 to 2005. During this period, the incidence of exocrine pancreatic cancer generally decreased whereas the incidence of endocrine pancreatic cancer increased. This difference in trends by histology was evident across age, gender, and racial groups. It was also evident among different racial/ethnic groups using data from 1992 to 2005. Variation in trends was observed by stage. The incidence of exocrine cancers declined for all stages except regional. Endocrine cancer incidence increased for all tumor stages, and the increase was most prominent for localized tumors. When exocrine tumors were stratified by tumor subsite, the incidence of cancers in the tail and body regions increased while the incidence in other regions decreased. While better detection and classification of tumors through improved diagnostic procedures may be related to these changing trends, etiologic factors warrant study.

Pancreatic islet cell carcinoma presenting with concurrent Cushing's and Zollinger-Ellison syndromes: case series and literature review.

Cushing's syndrome and Zollinger-Ellison syndrome occur occasionally as a result of neuroendocrine cancers. The concurrence of the two syndromes has been considered to confer a poor clinical and therapeutic outcome. In this study, we are reviewing two patients with pancreatic islet cell carcinomas and with both Zollinger-Ellison and Cushing's syndromes, one followed up for more than 5 years, and the other still receiving therapy, 5 years since diagnosis. A literature review showed that surgery has limited utility as the majority of these patients had metastases at the time of diagnosis. Proton-pump inhibitors, ketoconazole, and somatostatin antagonists have a major role in controlling symptoms. Interferon and systemic chemotherapeutic agents play a role in the management of metastatic and fast-growing cases. Chemoembolization and bland embolization show encouraging results in controlling liver metastases. The latter was used effectively and more than once in the two patients presented herein. On the basis of recent molecular genetics studies, target therapy may be helpful, however, ongoing trials will define it's utility. As the data confers a worse prognosis versus other pancreatic neuroendocrine tumors, the relatively favorable outcome of the two patients reported herein may reflect the impact of multiple therapeutic modalities.

Hypoglycemia associated with the production of insulin-like growth factor II in a pancreatic islet cell tumor: a case report.

An insulinoma is characterized by endogenous hyperinsulinemia and hypoglycemia. However, it has been reported that insulinomas with normal levels of plasma insulin and a normal insulin to glucose ratio occur in patients with hypoglycemia. Although overproduction of Insulin-like growth factor II (IGF-II) by non-islet cell tumors such as large mesenchymal tumors, can cause hypoglycemia, no cases of circulating plasma IGF-II from an islet cell tumor contributing to hypoglycemia have been reported. We report here a rare case of a pancreatic islet tumor in a patient with hypoglycemia that was associated with increased plasma IGF-II, which returned to normal after tumor resection.

[Case of pancreatic endocrine tumor associated with Cushing's syndrome].

A 78-year-old woman was admitted complaining of edema of the bilateral lower extremities and face. Computed tomography (CT) and ultrasonography (US) of her abdomen revealed a pancreatic tumor and multiple liver metastases. After admission, hypokalemia and muscle weakness and edema of the bilateral lower extremities rapidly worsened. The diagnosis of Cushing's syndrome was established based on clinical and biochemical data and endocrine studies. We thought that the primary tumor was a pancreatic endocrine tumor based on the liver tumor biopsy findings, and that the pancreatic tumor and liver metastatic tumors were ectopic ACTH-producing tumors. A case of pancreatic endocrine tumor associated with Cushing's syndrome is relatively rare. We summarize previous reports.

Portal vein resection for a portal vein thrombus caused by nonfunctioning islet cell carcinoma: report of a case.

We report a case of nonfunctioning islet cell carcinoma of the pancreas causing a tumor thrombus in the portal vein. The patient was a 60-year-old woman whose presenting symptoms were abdominal pain, vomiting, and weight loss. We performed a subtotal pancreatectomy and splenectomy combined with partial resection of the portal vein. Histopathological studies confirmed the diagnosis of nonfunctioning islet cell carcinoma of the pancreas with a tumor thrombus in the portal vein. The patient's postoperative course was uneventful and she is doing well 25 months after the operation.

Malignant pancreatic endocrine tumor in a child with tuberous sclerosis.

Tuberous sclerosis complex (TSC) is an autosomal dominant condition whose signs and symptoms may vary from a few hypopigmented skin spots to epilepsy, severe mental retardation, and renal failure. The disease is caused by mutations in either TSC1 or TSC2 gene, at chromosome 9q34 and 16p13.3. Inactivation of both alleles at TSC1 or TSC2 loci is associated with the development of hamartomas in different organs, and only rarely with malignant neoplasms. In this study we present a 6-year-old boy with TSC and with a malignant islet cell tumor of the pancreas. Mutation analysis of DNA extracted from peripheral blood cells of the patient identified an R1459X de novo mutation in exon 33 of the TSC2 gene. Immunohistochemical analysis with anti-tuberin antibodies on paraffin-embedded tissue sections showed loss of tuberin immunostaining in tumor cells but normal expression in residual normal pancreas. DNA analysis of tumor and normal cells showed chromosome 16p13 loss of heterozygosity in malignant pancreatic islet cell tumor but not in normal pancreas. These findings suggest a role for tuberin, the TSC2 gene product, in the pathogenesis of malignant pancreatic endocrine tumor.

Octreotide-sensitive ectopic ACTH production by islet cell carcinoma with multiple liver metastases.

We report a 21-year-old woman with ectopic ACTH syndrome due to islet cell carcinoma with multiple liver metastases. On admission, she showed Cushingoid appearance (moon face, central obesity etc.) and had acute respiratory distress syndrome due to pneumocystis carinii pneumonia. Laboratory examination revealed marked elevations of plasma ACTH (735 pg/ml) and cortisol (145 microg/dl) with a profound hypokalemia (2.0 mEq/l). She was found to have multiple masses in the liver and a solid mass in the tail of pancreas by abdominal computerized tomography scanning. Treatment with octreotide successfully reduced elevated plasma ACTH and cortisol levels, and she received frequent transhepatic arterial embolization and chemotherapy. The primary pancreatic tumor was surgically removed, revealing islet cell carcinoma which contained high content of ACTH (100 microg/g wet weight) and abundantly expressed proopiomelanocortin and somatostatin receptor subtype-2 mRNAs as determined by Northern blot analysis. Postoperatively, she was free from symptoms for almost one year. However, progressive enlargement of multiple liver metastases refractory to chemotherapy led her to decide on total hepatectomy and liver transplantation from her father. After liver transplantation, she remained almost free from symptoms for almost one year. However, metastases developed to the mediastinal and paraaortic lymph nodes as detected by 111[In] pentetreotide scintigraphy. Eleven months after liver transplantation, she was again treated with octreotide and, 16 months after, with metyrapone, both of which were effective in reducing ACTH and cortisol levels, respectively, until she died of acute respiratory failure. This case of a young female patient with ectopic ACTH-producing islet cell carcinoma of the pancreas was quite unique in that she survived for 5 years despite the acute onset and rapid progression of the multiple liver metastases at least in part due to the long-lasting favorable response to octreotide and living-related liver transplantation.

Hepatic encephalopathy secondary to transtumoral portal-hepatic venous shunting.

Intrahepatic portal-systemic shunts causing hepatic encephalopathy are very rare. This is a case report of a patient with hepatic metastases of a pancreatic islet cell tumor that manifested with transtumoral shunts leading to hepatic encephalopathy. The diagnosis was confirmed with Doppler ultrasound and initially treated with selective transhepatic portal vein embolization followed by hepatic artery embolization, and eventually radiofrequency ablation of the largest metastases. Despite excellent short-term palliation, symptom recurrence necessitated liver resection, the results of which proved durable. A multidisciplinary treatment plan for the identification and management of potentially salvageable encephalopathy in similar patients is described.

Review of the clinical, histological, and molecular aspects of pancreatic endocrine neoplasms.

Pancreatic endocrine neoplasms (PENs) are rare tumors, and little is known about their genetic and chromosomal alterations. Elucidation of the molecular events involved in PEN carcinogenesis has been hindered by the fact that PENs have been considered a single disease entity. The emergence of novel molecular characterization strategies has, however, made it apparent that these lesions exhibit diverse molecular fingerprints, which will facilitate the precise delineation of PEN prognosis, histopathology, and carcinogenesis.

Hyperparathyroidism, humoral hypercalcemia of malignancy, and the anabolic actions of parathyroid hormone and parathyroid hormone-related protein on the skeleton.

So what have we learned from the Takeuchi case? It has been 80 years since malignancy-associated hypercalcemia was described. It has been 45 years since HHM was first described. It has been 15 years since PTHrP was identified, and 12 years since PTHrP immunoassays became available for clinical research. We now know almost everything about HHM in pathophysiological terms, and we can reproduce the cardinal features of the syndrome in laboratory animals and humans. The Takeuchi case reminds us that we still have a few things to learn about HHM. Specifically, "Why is the regulation of 1,25(OH)2D different in patients with HHM and HPT?" and "Why is normal osteoblast-osteoclast coupling dysregulated in HHM?" or more fundamentally, "What regulates osteoblast-osteoclast coupling, and why is it deranged in HHM?" Given the rate of accumulation of new information about HHM, about the anabolic effects of PTH and PTHrP, and about osteoblast-osteoclast coupling over the past 10 years, there is reason to be optimistic that the answers to these questions will soon become clear.

Parathyroid hormone-related protein induced coupled increases in bone formation and resorption markers for 7 years in a patient with malignant islet cell tumors.

Parathyroid hormone-related protein (PTHrP) and PTH share the common PTH/PTHrP receptor. Although an elevated level of circulating PTHrP in patients with malignancies causes hypercalcemia as does PTH, chronic and systemic effects of PTHrP on bone metabolism in humans are not well understood because tumor-burden patients showing hypercalcemia usually have a poor prognosis. We investigated bone and calcium metabolism in a patient with malignant islet cell tumors showing hypercalcemia due to the elevated plasma PTHrP level for 7 years. Hypercalcemia and hypercalciuria continued throughout the clinical course in spite of frequent infusions of bisphosphonates. Bone resorption markers and a bone formation marker were consistently elevated as seen in primary hyperparathyroidism, a disease caused by an autonomous hypersecretion of PTH. Based on biochemical measurements including bone markers and serum 1,25-dihydroxyvitamin D, the clinical features of this case essentially are the same as those of primary hyperparathyroidism except for the elevated level of plasma PTHrP with suppressed intact PTH level. Therefore, it is suggested that chronic and systemic effects of PTHrP on bone as well as calcium metabolism are indistinguishable from those of PTH in human.

Nonfunctioning islet cell tumor presenting with ascites and portal hypertension.

Nonfunctioning islet cell tumors commonly cause no symptoms. A 22-year-old woman presented with lump in the left hypochondrium, refractory high-protein ascites and evidence of left-sided portal hypertension. At exploratory laparotomy, a 30 cm x 15 cm mass was seen at the splenic hilum, with large collateral vessels around. Distal pancreatectomy with splenectomy was done. Histology of the mass showed malignant islet cell tumor infiltrating the spleen. The patient died in the postoperative period.

[Fluid-fluid level in a non functioning and hemorragic neuro-endocrine islet-cell tumor of the pancreas: MRI features]. / Niveau liquide-liquide dans une tumeur neuro-endocrine du pancréas non fonctionnelle et hémorragique: aspects en IRM.

The authors report the MR features of a non functioning and hemorragic islet-cell tumor of the pancreas. This tumor was composed of a central cystic component with a fluid-fluid level seen on T1- and T2-weighted images and a peripheral hypervascular soft tissue component which showed hyperintensity on T2-weighted images with fat saturation.

Nonfunctioning islet cell carcinoma of the pancreas associated with massive intra-abdominal hemorrhage.

Pancreatic islet cell tumors are rarely associated with intra-abdominal hemorrhage. We report herein a rare case of nonfunctioning islet cell carcinoma associated with massive hemorrhage into the abdominal cavity caused by spontaneous rupture of the tumor. A 44-year-old man presenting with sudden upper abdominal pain was admitted to his local hospital on April 18, 1994. On April 19, a laparotomy was performed with the diagnosis of peritonitis. Massive hemorrhage of unknown origin occurred, and he was transferred to our hospital in a state of hypovolemic shock. Imaging findings revealed massive hematoma in the abdominal cavity and a hypervascular tumor arising from the body of the pancreas. Because the hemorrhage was life-threatening, an emergent re-laparotomy was performed on April 20. Apart from the massive hemorrhage, a pancreatic tumor (60 x 35 x 30 mm in size) with spontaneous rupture was noted. Distal pancreatectomy, combined with splenectomy and removal of the hematoma, was performed. Histological findings revealed an islet cell carcinoma of the pancreas with venous invasion. Peritoneal dissemination, liver metastasis, and lymph node metastasis were not observed. The patient is alive without recurrence 6 years and 5 months after the operation.