Preoperative diabetes mellitus and long-term survival after resection of pancreatic adenocarcinoma.

PURPOSE: To assess clinicopathologic features and postresection survival of diabetes mellitus (DM)-associated pancreatic ductal adenocarcinoma (PDAC). METHODS: Records of resected PDAC patients from 2000 to 2007 were reviewed. DM was classified as new-onset (<24 months before PDAC) or longstanding (> or =24 months). Clinicopathologic features were compared by univariate and multivariate analyses. Survival was assessed by Kaplan-Meier method and Cox regression. RESULTS: Of 209 patients, 93 (45%) met criteria for DM (35 longstanding DM, 55 new-onset DM, 3 duration unknown). DM patients were older (DM 66 +/- 9 years, non-DM 63 +/- 12 years, P = 0.06); a majority had additional preoperative comorbidities (DM 64.5%, non-DM 25.9%, P < 0.001). Tumor size was larger in patients with DM (DM 3.8 +/- 1.7 cm, non-DM 3.2 +/- 1.5 cm, P = 0.003). Groups were similar in terms of tumor location, perineural/lymphovascular invasion, and node and margin status. On logistic regression, tumor size >/=3.0 cm was independently associated with both overall DM (odds ratio [OR] 3.60; 95% confidence interval [1.79-7.26]) and new-onset DM (OR 3.69, [1.65-8.24]). Median survival was reduced in patients with DM compared with non-DM (15 versus 17 months, P = 0.015). Multivariate analysis controlling for prognostic variables including age, comorbidities, and tumor size demonstrated that DM was independently associated with reduced survival (hazard ratio [HR] 1.55, [1.02-2.35]). This association was more pronounced for patients with new-onset DM (HR 1.75 [1.10-2.78]) than those with longstanding DM (HR 1.30 [0.75-2.25]). CONCLUSIONS: Preexisting DM is associated with reduced survival in patients undergoing resection for PDAC. PDAC with new-onset DM may exhibit increased tumor size and decreased postresection survival. Additional investigation is needed to clarify etiology and impact of PDAC-associated DM.

Factors associated with recurrence and survival following hepatectomy for large hepatocellular carcinoma: a multicenter analysis.

BACKGROUND: Optimal management of large (>5 cm) hepatocellular carcinoma (HCC) remains controversial. We sought to determine the factors associated with recurrence and survival for patients with large HCC following hepatectomy. METHODS: An analysis of a combined prospective database from two tertiary care centers was performed on consecutive patients who underwent hepatectomy for HCC > 5 cm. Univariate and multivariate analyses were performed to determine factors associated with recurrence, disease-free (DFS) and overall survival (OS). RESULTS: Seventy-eight patients were identified: 32 (41%) had hepatic fibrosis. Forty-six patients (59%) underwent a major hepatectomy with a morbidity rate of 41% and a mortality rate of 13%. Fibrosis was associated with male gender (P = 0.045), hepatitis C (P = 0.003), higher Child-Pugh (P < 0.0001) and Okuda score (P = 0.002), smaller tumors (6.25 cm vs. 10.5 cm; P < 0.001), positive-margin resection (P = 0.01), and death (P = 0.047). Factors associated with recurrence include tumor multifocality (P = 0.03) and vascular invasion (P = 0.02). Predictors of OS include multifocal tumors (P = 0.05), margin status (P = 0.02), vascular invasion (P = 0.01), and treatment complications (P = 0.004). The median overall DFS and OS were 12 and 20 months, respectively. Fibrosis had no impact on DFS (P = 0.24) or OS (P = 0.20). CONCLUSIONS: For patients with HCC larger than 5 cm, tumor-related factors predict outcomes and survival.

Comparison of yttrium-90 radioembolization and transcatheter arterial chemoembolization for the treatment of unresectable hepatocellular carcinoma.

PURPOSE: To compare the effectiveness and toxicity of transcatheter arterial chemoembolization (chemoembolization) and yttrium-90-labeled microspheres (radioembolization) in patients with unresectable hepatocellular carcinoma (HCC). MATERIALS AND METHODS: Outcomes from patients who underwent radioembolization or chemoembolization as the only treatment for unresectable HCC from 1996 to 2006 were compared. Response was assessed with Response Evaluation Criteria in Solid Tumors, survival was assessed with the Kaplan-Meier method, and toxicity was graded with National Cancer Institute criteria. Multivariate analysis for factors affecting survival was performed. RESULTS: Seventy-one patients were treated with either chemoembolization (n = 44, 62%) or radioembolization (n = 27, 38%). Treatment groups were similar in age, sex, Child class, Model for End-Stage Liver Disease score, tumor size, and vascular invasion. Progressive disease at 3 months was observed in 16 (36%) of the 44 patients treated with chemoembolization and nine (33%) of the 27 patients treated with radioembolization (P = not statistically significant). The median overall survival was similar for both groups (6 months with chemoembolization vs 6 months with radioembolization, P= .7). Grade 3 or higher toxicity was observed in 24 of the 71 patients (34%). Tumor multifocality, vascular invasion, and hepatitis C seropositivity were independently associated with worse survival, whereas method of treatment was not. CONCLUSIONS: In this single-center study, preliminary evidence suggests that chemoembolization and radioembolization provided similar effectiveness and toxicity in patients with unresectable HCC.

Combined nephrectomy and major hepatectomy: indications, outcomes, and recommendations.

BACKGROUND: Simultaneous nephrectomy with major hepatectomy (NMH) is uncommon. We reviewed our experience with NMH. STUDY DESIGN: Records of patients who underwent NMH at Emory Hospital between January 1995 and May 2008 were examined. Patients undergoing resection of three or more liver segments at the same setting as a total nephrectomy were included. Indications and outcomes were assessed. RESULTS: Twenty patients underwent NMH. Mean (+/- SD) age was 59.9+/-12.8 years, 6 (30%) were women, and 15 (75%) presented with comorbidities. Most kidney neoplasms were renal cell carcinomas of the right kidney (n=16, 80%) with a mean diameter of 10.0+/-6.1 cm. Eight patients (40%) also underwent thrombectomy for inferior vena cava tumor thrombus. The most common indications for hepatectomy were direct liver invasion in eight patients (40%) and distant hepatic metastases in nine (45%); liver tumors were 4.2+/-3.3 cm (mean +/- SD) in diameter. Mean (+/- SD) operative time was 8.3+/-2.6 hours. Liver resections included 15 (75%) right hepatectomies and 5 (25%) left hepatectomies. In all cases, tumor negative hepatic margins were achieved. Median operative blood loss was 1,700 mL (range 200 to 8,000 mL). Ten patients (50%) suffered complications in the postoperative period; three of these suffered major complications, resulting in one perioperative death (5%). Mean hospital stay was 12+/-8.8 days. Overall survival was 25 months (range 0 to 34 months). CONCLUSIONS: In this large series of nephrectomy with simultaneous major hepatectomy, morbidity and mortality were acceptable. In specialized centers NMH may be considered in properly selected patients for combined resection for synchronous neoplasms of the kidney and liver.

Arterial and venous resection for pancreatic adenocarcinoma: operative and long-term outcomes.

HYPOTHESIS: Aggressive preoperative and intraoperative management may improve the resectability rates and outcomes for locally advanced pancreatic adenocarcinoma with venous involvement. The efficacy and use of venous resection and especially arterial resection in the management of pancreatic adenocarcinoma remain controversial. DESIGN: Retrospective review of patients entered into prospective databases. SETTING: Two tertiary referral centers. PATIENTS AND METHODS: A retrospective review of 2 prospective databases of 593 consecutive pancreatic resections for pancreatic adenocarcinoma from January 1, 1999, through May 1, 2007. RESULTS: Of the 593 patients, 36 (6.1%) underwent vascular resection at the time of pancreatectomy. Thirty-one of the 36 (88%) underwent venous resection alone; 3 (8%), combined arterial and venous resection; and 2 (6%), arterial resection (superior mesenteric artery resection) alone. Patients included 18 men and 18 women, with a median age of 62 (range, 42-82) years. The 90-day perioperative mortality and morbidity rates were 0% and 35%, respectively, compared with 2% and 39%, respectively, for the group undergoing nonvascular pancreatic resection (P = .34). Median survival was 18 (range, 8-42) months in the vascular resection group compared with 19 months in the nonvascular resection group. Multivariate analysis demonstrated node-positive disease, tumor location (other than head), and no adjuvant therapy as adverse prognostic variables. CONCLUSIONS: In this combined experience, en bloc vascular resection consisting of venous resection alone, arterial resection alone, or combined vascular resection at the time of pancreatectomy for adenocarcinoma did not adversely affect postoperative mortality, morbidity, or overall survival. The need for vascular resection should not be a contraindication to surgical resection in the selected patient.

Changing management and outcome of hepatocellular carcinoma: evaluation of 501 patients treated at a single comprehensive center.

BACKGROUND: We evaluated changes in therapy and outcome for patients with hepatocellular carcinoma (HCC) over time in a large cohort of Western patients managed at one U.S. medical center. METHODS: A retrospective analysis of all patients with HCC treated at one U.S. medical center was performed. Analyses were stratified by time intervals 1990-1996 (pre-Milan) and 1997-2004 (post-Milan) to examine impact of UNOS criteria adapted from the post-Milan experience with OLT on treatment and survival. RESULTS: From 1990 to 2004, 501 patients were identified, 170 (34%) pre-Milan and 331 (66%) post-Milan. Seventy-four (15%) underwent OLT, 99 (20%) had partial hepatectomy (PH), 51 (10%) had ablative therapy (Ablate), 84 (16%) had embolic treatment (Embo), and 194 (39%) had chemotherapy or supportive care (C/SC). Median survival for all patients was 11 months. By time interval, median overall survival (OS) was better for post-Milan patients as compared with the pre-Milan group (13 months vs. 7 months, P = 0.02). On multivariate analysis OLT had the strongest association with improved survival of all factors examined (Odds ratio 12.4, 95% CI 7.7-20.5). CONCLUSIONS: In this series, treatment post-1996 is associated with improved survival, likely due to improvements in selection criteria and outcomes for liver transplantation.

Saphenous vein graft conduits for insertion of hepatic arterial infusion pumps in patients with abnormal hepatic arterial anatomy.

BACKGROUND AND OBJECTIVES: Hepatic arterial infusion (HAI) chemotherapy offers improved hepatic control for liver metastases from colon cancer. Optimal catheter insertion requires an adequate gastroduodenal artery (GDA). Limited data exists on using saphenous vein grafts (SVG) as conduits when native vasculature is inadequate. METHODS: All HAI pump insertions from 7/99 to 7/03 requiring SVG conduits (N = 10) were analyzed for arterial anatomy, operative conduct, and outcome. RESULTS: From 1988 through 2005, 124 HAI pumps were placed of which 10 received SVG conduits to optimize placement. Mean operative time was 251 +/- 50 min and mean blood loss was 230 +/- 30 cm(3). All were placed with palliative intent. Three patients (30%) had type 1 anatomy with inadequate GDA. Five (50%) had type 3 anatomy with replaced right hepatic artery, one (10%) had a small GDA originating off the right hepatic artery, and one patient (10%) had a trifurcation. Two (20%) pump-related complications were identified, and only one (10%) was related to vasculature (catheter thrombosis as a result of hepatic arterial stenosis distal to the SVG insertion site). CONCLUSIONS: Complication rates related to SVG conduits for hepatic arterial infusion pump placement are low. Saphenous vein grafts are acceptable conduits for patients with abnormal hepatic arterial anatomy.

Neurotensin-deficient mice have deficits in prepulse inhibition: restoration by clozapine but not haloperidol, olanzapine, or quetiapine.

Prepulse inhibition (PPI) of the acoustic startle reflex is a commonly used measure of preattentive sensorimotor gating. Disrupted PPI in rodents represents an animal model of the sensorimotor gating deficits characteristic of schizophrenia. The neurotensin (NT) system is implicated in the pathophysiology of schizophrenia, and NT has been hypothesized to act as an endogenous antipsychotic. In rats, NT receptor agonists restore PPI disrupted by dopamine receptor agonists and N-methyl-D-aspartate receptor antagonists, and pretreatment with an NT receptor antagonist blocks restoration of isolation rearing induced deficits in PPI by some antipsychotic drugs. The current studies further scrutinized the role of the NT system in the regulation of PPI and in antipsychotic drug-induced restoration of PPI using NT-null mutant mice (NT-/-). NT-/- mice exhibited significantly higher pulse alone startle amplitudes and disrupted PPI compared with NT+/+ mice. Haloperidol (0.1 mg/kg) and quetiapine (0.5 mg/kg) administered 30 min before PPI testing significantly increased PPI in NT+/+ mice but had no effect on PPI in NT-/- mice. In contrast, clozapine (1.0 mg/kg) significantly increased PPI in both NT-/- and NT+/+ mice, whereas olanzapine (0.5 mg/kg) had no effect on PPI in either NT-/- or NT+/+ mice. In a separate experiment, amphetamine (2.0 mg/kg i.p.) significantly disrupted PPI in NT+/+ mice but not NT-/- mice. These results provide evidence that the effects of antipsychotic drugs (APDs) may be differentially affected by the state of NT neurotransmission and, moreover, that APDs differ in their dependence on an intact NT system.