Pancreatic adenocarcinoma: a pilot study of quantitative perfusion and diffusion-weighted breath-hold magnetic resonance imaging.

PURPOSE: To confirm the feasibility of breath-hold DCE-MRI and DWI at 3T to obtain the intra-abdominal quantitative physiologic parameters, K(trans), k ep, and ADC, in patients with untreated pancreatic ductal adenocarcinomas. METHODS: Diffusion-weighted single-shot echo-planar imaging (DW-SS-EPI) and dynamic contrast-enhanced (DCE) MRI were used for 16 patients with newly diagnosed biopsy-proven pancreatic ductal adenocarcinomas. K(trans), k ep, and apparent diffusion coefficient (ADC) values of pancreatic tumors, non-tumor adjacent pancreatic parenchyma (NAP), liver metastases, and normal liver tissues were quantitated and statistically compared. RESULTS: Fourteen patients were able to adequately hold their breath for DCE-MRI, and 15 patients for DW-SS-EPI. Four patients had liver metastases within the 6 cm of Z axis coverage centered on the pancreatic primary tumors. K(trans) values (10(-3) min(-1)) of primary pancreatic tumors, NAP, liver metastases, and normal liver tissues were 7.3 ± 4.2 (mean ± SD), 25.8 ± 14.9, 8.1 ± 5.9, and 45.1 ± 15.6, respectively, k ep values (10(-2) min(-1)) were 3.0 ± 0.9, 7.4 ± 3.1, 5.2 ± 2.0, and 12.1 ± 2.8, respectively, and ADC values (10(-3) mm(2)/s) were 1.3 ± 0.2, 1.6 ± 0.3, 1.1 ± 0.1, and 1.3 ± 0.1, respectively. K(trans), k ep, and ADC values of primary pancreatic tumors were significantly lower than those of NAP (p < 0.05), while K(trans) and k ep values of liver metastases were significantly lower than those of normal liver tissues (p < 0.05). CONCLUSIONS: 3T breath-hold quantitative physiologic MRI is a feasible technique that can be applied to a majority of patients with pancreatic adenocarcinomas.

Bilateral adrenal gland enlargement secondary to histoplasmosis mimicking adrenal metastases: diagnosis with EUS-guided FNA.

While adrenal gland histoplasmosis has been previously diagnosed by fine needle aspiration utilizing the percutaneous approach, EUS-FNA has not been employed in the diagnosis of this infection affecting both adrenal glands. We report a patient with massive bilateral adrenal enlargement due to histoplasmosis that was diagnosed by EUS-FNA. Trans-duodenal and trans-gastric fine needle aspiration biopsy of both adrenal glands was performed. Rapid onsite cytopathologic evaluation (ROSE) revealed epithelioid histiocytes, singly and in clusters consistent with granulomas. Apparent intracytoplasmic inclusions suggestive of organisms were visible. A Gomori Methenamine Silver stain (GMS) revealed abundant small intracellular budding yeasts, morphologically consistent with Histoplasma; the patient was admitted for amphotericin B intravenous infusion. His fever abated on the second day after amphotericin B was started. His urine Histoplasma antigen was positive. Fungal cultures from both adrenal EUS-FNA samples grew Histoplasma capsulatum. After a one week hospital stay, he was discharged home on itraconazole 200 mg po bid for one year. Four months after initiation of treatment, his urine Histoplasma antigen was undetectable. Nine months after initial diagnosis, the patient regained his energy level, and returned to work with complete resolution of his initial symptoms. This case highlights that EUS-FNA with ROSE can be a highly effective tool in the diagnosis of uncommon infections of the adrenal glands.

Laparoscopic and open distal pancreatectomy: a comparison of outcomes.

Laparoscopic (lap) pancreatic surgery has been increasingly reported since its introduction in 1992. A retrospective analysis of consecutive patients undergoing elective lap and open distal pancreatectomy from 2002 to 2007 was performed. Univariate analysis was completed to evaluate perioperative variables. Logistic regression analysis was used to model predictors of postoperative pancreatic fistula. One hundred forty-eight subjects underwent distal pancreatectomy; 98 completed open, 44 lap, and six converted to open. There was no significant difference in the incidence of postoperative morbidity or mortality between the surgical approaches. Decreased operative time (156 vs 200 minutes, P < 0.01), blood loss (157 vs 719 mL, P < 0.01), and length of stay (5.9 vs 8.6 days, P < 0.01) were seen in the lap group. There was no significant difference in the rate of all pancreatic fistula formation (50 vs 46%, P = 0.94) or clinically significant leaks (18 vs 19%, P = 0.97) between techniques. A preoperative biopsy-proven cancer, increasing body mass index, history of pancreatitis, and male gender were significant predictors of having a pancreatic fistula. Lap and open distal pancreatectomy are performed safely at high-volume pancreatic surgery centers. This report provides ongoing support of the feasibility and safety of the lap approach with improved perioperative outcomes and equivalent pancreatic fistula rate.

TRA-8 anti-DR5 monoclonal antibody and gemcitabine induce apoptosis and inhibit radiologically validated orthotopic pancreatic tumor growth.

PURPOSE: To evaluate agonistic TRA-8 monoclonal antibody to human death receptor 5 (DR5) and gemcitabine in vitro and in an orthotopic pancreatic cancer model. EXPERIMENTAL DESIGN: Pancreatic cancer cell lines were screened for DR5 expression, cytotoxicity, and apoptosis induced by TRA-8, gemcitabine, or gemcitabine and TRA-8. An orthotopic model of pancreatic cancer was established in severe combined immunodeficient mice. Mice were treated with TRA-8, gemcitabine, or a combination for one or two cycles of therapy. Tumor growth (ultrasound) and survival were analyzed. RESULTS: All five pancreatic cancer cell lines showed DR5 protein expression and varying sensitivity to TRA-8-mediated cytotoxicity. MIA PaCa-2 cells were very sensitive to TRA-8, moderately resistant to gemcitabine, with additive cytotoxicity to the combination. S2-VP10 cells were resistant to TRA-8 and sensitive to gemcitabine with synergistic sensitivity to the combination. Combination treatment in vitro produced enhanced caspase-3 and caspase-8 activation. A single cycle of therapy produced comparable efficacy for single-agent TRA-8 and the combination of TRA-8 and gemcitabine, with significant reduction in tumor size and prolonged survival compared with gemcitabine alone or control animals. With two cycles of therapy, TRA-8 and combination therapy produced enhanced inhibition of tumor growth compared with single-agent gemcitabine or untreated animals. However, the combination regimen showed enhanced survival as compared with single-agent TRA-8. CONCLUSIONS: Pancreatic cancer cell lines express varying levels of DR5 and differ in their sensitivity to TRA-8 and gemcitabine-induced cytotoxicity. TRA-8 with two cycles of gemcitabine therapy produced the best overall survival.