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.

Extra-hepatic hepatocellular carcinoma presenting as obstructive jaundice.

Hepatocellular carcinoma is a neoplasm with a uniformly poor prognosis. Risk factors for its development include chronic hepatitis B or C infection, haemochromatosis and alpha-1-antitrypsin deficiency, but individuals with any type of chronic liver disease are predisposed. The incidence is significantly higher in Asia and Africa although it has been noted to be increasing in the United States. We present a patient with notable atypical clinical features for hepatocellular carcinoma. The patient had neither predisposing risk factors nor a primary liver lesion causing obstructive jaundice. After multiple tissue specimens were obtained, the final pathological diagnosis was established. Hepatocellular carcinoma generally requires a surgical cure, but patients who are icteric often portend poorer prognoses. For those at high risk, screening may be indicated to identify early curative treatment.

Pharmacological ascorbate with gemcitabine for the control of metastatic and node-positive pancreatic cancer (PACMAN): results from a phase I clinical trial.

BACKGROUND: Treatment for pancreatic cancer with pharmacological ascorbate (ascorbic acid, vitamin C) decreases tumor progression in preclinical models. A phase I clinical trial was performed to establish safety and tolerability of pharmacological ascorbate combined with gemcitabine in patients with biopsy-proven stage IV pancreatic adenocarcinoma. DESIGN: Nine subjects received twice-weekly intravenous ascorbate (15-125 g) employing Simon's accelerated titration design to achieve a targeted post-infusion plasma level of ≥350 mg/dL (≥20 mM). Subjects received concurrent gemcitabine. Disease burden, weight, performance status, hematologic and metabolic laboratories, time to progression and overall survival were monitored. RESULTS: Mean plasma ascorbate trough levels were significantly higher than baseline (1.46 ± 0.02 vs. 0.78 ± 0.09 mg/dL, i.e., 83 vs. 44 µM, p < 0.001). Adverse events attributable to the drug combination were rare and included diarrhea (n = 4) and dry mouth (n = 6). Dose-limiting criteria were not met for this study. Mean survival of subjects completing at least two cycles (8 weeks) of therapy was 13 ± 2 months. CONCLUSIONS: Data suggest pharmacologic ascorbate administered concurrently with gemcitabine is well tolerated. Initial data from this small sampling suggest some efficacy. Further studies powered to determine efficacy should be conducted.