Thorvardur R. Halfdanarson

Pancreatic neuroendocrine tumors (PNETs): incidence, prognosis and recent trend toward improved survival

BACKGROUND Pancreatic neuroendocrine tumors (PNETs) are uncommon neoplasms that can present with symptoms of hormone overproduction. We evaluated the incidence, prognosis, and temporal trends of PNETs. PATIENTS AND METHODS We analyzed all cases of PNETs registered in the Surveillance, Epidemiology, and End Results database from 1973 to 2000. Age-adjusted incidence and survival rates were calculated and survival trends over time were evaluated. RESULTS We identified 1483 cases of PNETs. The crude annual incidence per 1,000,000 was 1.8 in females and 2.6 in males and increased with advancing age. The incidence increased over the study period. Most patients (90.8%) had nonfunctional tumors. Advanced stage, higher grade, and age were the strongest predictors of worse survival. Patients with functional tumors had better outcomes than patients with nonfunctional tumors in both univariate and multivariate analysis (P = 0.004). Survival time increased over the period from 1973 to 2000. No differences were seen in the distribution of stage or age at diagnosis among time periods. CONCLUSION PNETs are uncommon neoplasms but the incidence may be increasing. Age, grade, stage, and functional status predict survival in patients with PNETs. Survival has improved over time, but this is not explained by earlier diagnosis or stage migration.

Pancreatic endocrine neoplasms: epidemiology and prognosis of pancreatic endocrine tumors

Pancreatic endocrine tumors (PETs) are uncommon tumors with an annual incidence <1 per 100 000 person-years in the general population. The PETs that produce hormones resulting in symptoms are designated as functional. The majority of PETs are non-functional. Of the functional tumors, insulinomas are the most common, followed by gastrinomas. The clinical course of patients with PETs is variable and depends on the extent of the disease and the treatment rendered. Patients with completely resected tumors generally have a good prognosis, and aggressive surgical therapy in patients with advanced disease may also prolong survival. The epidemiology, prognosis, and established and novel prognostic markers of PETs are reviewed.

Hematological manifestations of copper deficiency: a retrospective review

Copper deficiency is an established cause of hematological abnormalities but is frequently misdiagnosed. Copper deficiency can present as a combination of hematological and neurological abnormalities and it may masquerade as a myelodysplastic syndrome. We reviewed the records of patients with hypocupremia and hematologic abnormalities identified between 1970 and 2005. Patients with hypocupremia unrelated to copper deficiency (e.g. Wilson’s disease) were excluded. Forty patients with copper deficiency and hematological abnormalities were identified. Ten patients (25%) had undergone bariatric (weight reduction) surgery and an additional 14 patients (35%) had undergone surgery on the gastrointestinal tract, most commonly gastric resection. In 12 cases, no cause for copper deficiency was identified. Anemia and neutropenia were the most common hematologic abnormalities identified and the majority of the patients also had neurologic findings, most commonly due to myeloneuropathy. Abnormalities observed on bone marrow examination including vacuoles in myeloid precursors, iron‐containing plasma cells, a decrease in granulocyte precursors and ring sideroblasts may be valuable clues to the diagnosis. Copper deficiency is an uncommon but very treatable cause of hematologic abnormalities.

A single-institution experience with 491 cases of small bowel adenocarcinoma

BACKGROUND The optimal treatment of small bowel adenocarcinoma is unknown. METHODS The records of 491 patients with small bowel adenocarcinoma diagnosis between 1970 and 2005 were reviewed for patient and tumor characteristics, treatment effects, and survival. RESULTS The median age at diagnosis was 62 years. The most common tumor locations were the duodenum (57%), jejunum (29%), and ileum (10%). The median overall survival was 20.1 months, with a 5-year overall survival of 26%. Greater age, male sex, higher stage and grade, residual disease after resection, and a lymph node ratio of 50% or greater predicted decreased overall survival in univariate analysis. Age and stage were predictive of survival in multivariate analysis. The overall survival with metastatic disease was poor. Adjuvant therapy was not associated with longer overall survival (P = .44). CONCLUSIONS The prognosis of patients with small bowel adenocarcinoma is poor. Complete resection provides the only means of cure, and the role for adjuvant therapy remains uncertain.

Oncologic Emergencies: Diagnosis and Treatment

Patients with malignancies are subject to developing a unique set of complications that require emergent evaluation and treatment. With the increasing incidence of cancer in the general population and improved survival, these emergencies will be more frequently encountered. Physicians must be able to recognize these conditions and institute appropriate therapy after a focused initial evaluation. The approach to definitive therapy is commonly multidisciplinary, involving surgeons, radiation oncologists, medical oncologists, and other medical specialists. Prompt interventions can be lifesaving and may spare patients considerable morbidity and pain. In this review, we discuss the diagnosis of and initial therapy for common emergencies in hematology and oncology.

Oral Cancer Chemotherapy: The Critical Interplay Between Patient Education and Patient Safety

Currently, 10% of cancer chemotherapy is prescribed to patients by means of an oral formulation, but, by 2013, this percentage is predicted to increase to 25%. Oral chemotherapy offers many advantages, including no need for sometimes painful intravenous access, no intravenous drug administration fees, more time at home for patients, and a greater sense of patient autonomy. However, oral cancer chemotherapy also poses challenges, many of which revolve around adherence and safety. These challenges are discussed here. There are few other circumstances in which patient education and the maintenance of institutional safety infrastructure play such an integral role in sustaining favorable cancer clinical outcomes.

Copper deficiency in celiac disease

Copper deficiency is an uncommonly reported complication of celiac disease that has not received much attention in recent years. Copper deficiency may result in anemia and thrombocytopenia and also irreversible myeloneuropathy if it is not detected and treated appropriately. The prevalence of copper deficiency in patients with celiac disease is unknown. We describe 5 patients with celiac disease and associated copper deficiency diagnosed at our institution in recent years. All 5 patients had neurologic complications of copper deficiency and 3 patients also presented with hematologic abnormalities. We also review the literature regarding copper deficiency in celiac disease.

Current Status and Perspectives of Targeted Therapy in Well-Differentiated Neuroendocrine Tumors

Although neuroendocrine tumors (NET) are a relatively rare malignancy, the reported incidence is increasing, and some of the current treatment options are limited in their efficacy. Standard first-line therapy for metastatic small bowel NET includes somatostatin analogs. Although these agents can provide symptom relief and can delay disease progression in many patients, ultimately, new treatments are required for patients with progressive disease. In recent years, there has been considerable interest in developing agents specifically targeted against some of the pathways known to be involved in cancer cell growth, survival and invasion. In 2011, the mammalian target of rapamycin (mTOR) inhibitor everolimus and the tyrosine kinase inhibitor sunitinib were approved for the treatment of pancreatic NET. Clinical trials evaluating novel targeted agents are ongoing, both as single agents and in combination regimens. We review the current clinical status of these potential new treatments and highlight those with particular promise for the management of well-differentiated NET.

The North American Neuroendocrine Tumor Society Consensus Guidelines for Surveillance and Medical Management of Midgut Neuroendocrine Tumors

Abstract There have been significant developments in diagnostic and therapeutic options for patients with neuroendocrine tumors (NETs). Key phase 3 studies include the CLARINET trial, which evaluated lanreotide in patients with nonfunctioning enteropancreatic NETs; the RADIANT-2 and RADIANT-4 studies, which evaluated everolimus in functioning and nonfunctioning NETs of the gastrointestinal tract and lungs; the TELESTAR study, which evaluated telotristat ethyl in patients with refractory carcinoid syndrome; and the NETTER-1 trial, which evaluated 177Lu-DOTATATE in NETs of the small intestine and proximal colon (midgut). Based on these and other advances, the North American Neuroendocrine Tumor Society convened a multidisciplinary panel of experts with the goal of updating consensus-based guidelines for evaluation and treatment of midgut NETs. The medical aspects of these guidelines (focusing on systemic treatment, nonsurgical liver-directed therapy, and postoperative surveillance) are summarized in this article. Surgical guidelines are described in a companion article.

Risk factors for pancreatic neuroendocrine tumors: a clinic-based case-control study.

Objectives Pancreatic neuroendocrine tumors (PNETs) are uncommon, and little is known about their risk factors and association with other cancers. We evaluated whether the following risk factors known to be associated with pancreatic adenocarcinoma are also associated with PNETs: smoking, alcohol use, family history of PNET, and other cancers, and personal history of diabetes as potential risk factors. Methods Patients with PNETs seen at Mayo Clinic Rochester between 2000 and 2011 were compared with controls seen for a general medical evaluation. Patients and controls completed the same questionnaires. After excluding insulinoma and high-grade PNETs, 355 cases were evaluated, and 309 were matched to 602 controls (2:1) on age, sex, and region of residence. Results Personal smoking history was not associated with PNETs. Alcohol use was less common among cases (54% vs 67%, P < 0.001). Cases were more likely to report a family member with sarcoma (P = 0.02), PNET (P = 0.02), gallbladder cancer (P = 0.02), ovarian cancer (P = 0.04), and gastric cancer (P = 0.01). There was no association with other cancers in family members. Diabetes was more commonly reported by cases than controls (19% vs 11%, P < 0.001). Conclusions With the exception of diabetes, risk factors that are associated with pancreatic adenocarcinoma are not risk factors for PNETs.