A phase 2 study of tasisulam sodium (LY573636 sodium) as second-line treatment for patients with unresectable or metastatic melanoma.

Background: Tasisulam sodium (hereafter, tasisulam) is a novel anticancer agent that induces apoptosis through the intrinsic pathway and has antiangiogenic activity in preclinical models. Tasisulam demonstrated activity across a broad range of tumors, including melanoma. The primary objective of this phase 2 study was to determine the objective response rate (ORR) in patients who had received 1 previous systemic chemotherapy for unresectable/metastatic melanoma; secondary objectives were to evaluate the clinical response rate (CRR), progression-free survival (PFS), overall survival (OS), duration of response, safety, and pharmacokinetics.

Prevalence of CDKN2A mutations in pancreatic cancer patients: implications for genetic counseling.

Germline mutations in CDKN2A have been reported in pancreatic cancer families, but genetic counseling for pancreatic cancer risk has been limited by lack of information on CDKN2A mutation carriers outside of selected pancreatic or melanoma kindreds. Lymphocyte DNA from consecutive, unselected white non-Hispanic patients with pancreatic adenocarcinoma was used to sequence CDKN2A. Frequencies of mutations that alter the coding of p16INK4 or p14ARF were quantified overall and in subgroups.

Fascial closure following percutaneous endovascular aneurysm repair.

Introduction: There are potential benefits of percutaneous over open femoral access for endovascular aneurysm repair (EVAR). Subsequent arterial closure using percutaneous devices is costly, whilst open repair risks potential wound complications and delayed discharge. The technique of fascial closure has perceived advantages but its efficacy is unclear.

Capecitabine and temozolomide: design, implementation, and preliminary outcomes from a pilot project to ensure safe prescribing of oral chemotherapy.

Without adequate safety measures, oral chemotherapy can lead to undetected dosing errors. The Mayo Clinic launched a project to ensure that all capecitabine and temozolomide prescriptions receive an independent double check.

Obesity adversely affects survival in pancreatic cancer patients.

Background: Higher body-mass index (BMI) has been implicated as a risk factor for developing pancreatic cancer, but its effect on survival has not been thoroughly investigated. The authors assessed the association of BMI with survival in a sample of pancreatic cancer patients and used epidemiologic and clinical information to understand the contribution of diabetes and hyperglycemia.

Methods: A survival analysis using Cox proportional hazards by usual adult BMI was performed on 1861 unselected patients with pancreatic adenocarcinoma; analyses were adjusted for covariates that included clinical stage, age, and sex.

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.

Intra- and interobserver variability of target vessel measurement for fenestrated endovascular aneurysm repair.

Purpose: To evaluate intra- and interobserver agreement of target vessel measured from computed tomography (CT) scans with 2 measuring techniques used in planning fenestrated endovascular aneurysm repairs (FEVAR): multiplanar reconstruction (MPR) and semi-automated central lumen line (CLL).

Methods: CT datasets from 25 FEVAR patients were independently analyzed by 2 experienced observers according to a standardized protocol using the MPR (Leonardo workstation) and CLL (Aquarius workstation) techniques for each patient. Longitudinal vessel separation and clock-face position of the visceral aortic branches were measured twice.

Insulator-to-conducting transition in dense fluid helium.

By combining diamond-anvil-cell and laser-driven shock wave techniques, we produced dense He samples up to 1.5 g/cm(3) at temperatures reaching 60 kK. Optical measurements of reflectivity and temperature show that electronic conduction in He at these conditions is temperature-activated (semiconducting).

Anthropometric measures, body mass index, and pancreatic cancer: a pooled analysis from the Pancreatic Cancer Cohort Consortium (PanScan).

Background: Obesity has been proposed as a risk factor for pancreatic cancer.

Methods: Pooled data were analyzed from the National Cancer Institute Pancreatic Cancer Cohort Consortium (PanScan) to study the association between prediagnostic anthropometric measures and risk of pancreatic cancer. PanScan applied a nested case-control study design and included 2170 cases and 2209 control subjects.

A crucial role for Kupffer cell-derived galectin-9 in regulation of T cell immunity in hepatitis C infection.

Approximately 200 million people throughout the world are infected with hepatitis C virus (HCV). One of the most striking features of HCV infection is its high propensity to establish persistence (approximately 70-80%) and progressive liver injury. Galectins are evolutionarily conserved glycan-binding proteins with diverse roles in innate and adaptive immune responses.

Adjunctive iliac stents reduce the risk of stent-graft limb occlusion following endovascular aneurysm repair with the Zenith stent-graft.

Purpose: To determine whether the introduction of a policy of adjunctive stent insertion based on preoperative CT assessment or completion angiography reduced the incidence of limb occlusion after stent-graft implantation for endovascular aneurysm repair (EVAR).

Methods: A tertiary referral unit's endovascular database was retrospectively interrogated to compare the incidence of endograft limb occlusion in Zenith grafts following the introduction of a policy of selective adjunctive stent insertion. Group A included 288 limbs at risk in 146 patients (134 men; mean age 74+/-8 years) treated prior to August 2005 in whom adjunctive stents were inserted on an ad hoc basis only.

A genome-wide association study identifies pancreatic cancer susceptibility loci on chromosomes 13q22.1, 1q32.1 and 5p15.33.

We conducted a genome-wide association study of pancreatic cancer in 3,851 affected individuals (cases) and 3,934 unaffected controls drawn from 12 prospective cohort studies and 8 case-control studies. Based on a logistic regression model for genotype trend effect that was adjusted for study, age, sex, self-described ancestry and five principal components, we identified eight SNPs that map to three loci on chromosomes 13q22.1, 1q32.

Association of mitotic regulation pathway polymorphisms with pancreatic cancer risk and outcome.

Background: Mitosis is a highly regulated process that serves to ensure the fidelity of cell division. The disruption of mitotic regulators leading to aneuploidy and polyploidy is commonly observed in cancer cells. Single nucleotide polymorphisms (SNP) in regulators of mitosis may promote chromosome missegregation and influence pancreatic cancer and/or survival.

Family history of cancer and risk of pancreatic cancer: a pooled analysis from the Pancreatic Cancer Cohort Consortium (PanScan).

A family history of pancreatic cancer has consistently been associated with increased risk of pancreatic cancer. However, uncertainty remains about the strength of this association. Results from previous studies suggest a family history of select cancers (i.

A computerized, self-administered questionnaire to evaluate posttraumatic stress among firefighters after the World Trade Center collapse.

Objectives: We sought to determine the frequency of psychological symptoms and elevated posttraumatic stress disorder (PTSD) risk among New York City firefighters after the World Trade Center (WTC) attack and whether these measures were associated with Counseling Services Unit (CSU) use or mental health-related medical leave over the first 2.5 years after the attack.

Methods: Shortly after the WTC attack, a computerized, binary-response screening questionnaire was administered.

Cystic fibrosis transmembrane conductance regulator (CFTR) gene mutations and risk for pancreatic adenocarcinoma.

Background: Mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene are common in white persons and are associated with pancreatic disease. The purpose of this case-control study was to determine whether CFTR mutations confer a higher risk of pancreatic cancer.

Methods: In a case-control study, the authors compared the rates of 39 common cystic fibrosis-associated CFTR mutations between 949 white patients with pancreatic adenocarcinoma and 13,340 white controls from a clinical laboratory database for prenatal testing for CFTR mutations.

Association of breast cancer susceptibility variants with risk of pancreatic cancer.

Background: A number of susceptibility genes are common to breast and pancreatic cancer. Recently, several breast cancer susceptibility loci have been identified through genome-wide association studies. Here we evaluated possible associations between these single nucleotide polymorphisms (SNP) and pancreatic cancer risk.

Fluorescence in situ hybridization to visualize genetic abnormalities in interphase cells of acinar cell carcinoma, ductal adenocarcinoma, and islet cell carcinoma of the pancreas.

Objective: To use fluorescence in situ hybridization (FISH) to visualize genetic abnormalities in interphase cell nuclei (interphase FISH) of acinar cell carcinoma, ductal adenocarcinoma, and islet cell carcinoma of the pancreas.

Patients And Methods: Between April 4, 2007, and December 4, 2008, interphase FISH was used to study paraffin-embedded preparations of tissue obtained from 18 patients listed in the Mayo Clinic Biospecimen Resource for Pancreas Research with a confirmed diagnosis of acinar cell carcinoma, ductal adenocarcinoma, islet cell carcinoma, or pancreas without evidence of neoplasia. FISH probes were used for chromosome loci of APC (see glossary at end of article for expansion of all gene symbols), BRCA2, CTNNB1, EGFR, ERBB2, CDKN2A, TP53, TYMP, and TYMS.

Polymorphic variants in hereditary pancreatic cancer genes are not associated with pancreatic cancer risk.

Background: Inherited risk of pancreatic cancer has been associated with mutations in several genes, including BRCA2, CDKN2A (p16), PRSS1, and PALB2. We hypothesized that common variants in these genes, single nucleotide polymorphisms (SNP), may also influence risk for pancreatic cancer development.

Methods: A clinic-based case-control study in non-Hispanic white persons compared 1,143 patients with pancreatic adenocarcinoma with 1,097 healthy controls.

Genome-wide association study identifies variants in the ABO locus associated with susceptibility to pancreatic cancer.

We conducted a two-stage genome-wide association study of pancreatic cancer, a cancer with one of the lowest survival rates worldwide. We genotyped 558,542 SNPs in 1,896 individuals with pancreatic cancer and 1,939 controls drawn from 12 prospective cohorts plus one hospital-based case-control study. We conducted a combined analysis of these groups plus an additional 2,457 affected individuals and 2,654 controls from eight case-control studies, adjusting for study, sex, ancestry and five principal components.

Optimal technique for imaging iliac segments during endovascular repair of abdominal aortic aneurysms.

Purpose: To determine if oblique angulation of the image intensifier is adequate to image the entire length of the common iliac artery during endovascular aneurysm repair or if additional caudal tilt is necessary.

Methods: Using a 3D workstation, the apparent level of the iliac bifurcation (distal limit of the stent-graft) was determined on computed tomographic angiography by profiling the common iliac segment in oblique angulation only and repeated with a combination of oblique angulation and caudal tilt. Two independent observers measured twice the apparent length of the iliac segment in both profiles for 50 patients according to a set protocol.

Liver cyst cytokines promote endothelial cell proliferation and development.

Autosomal dominant polycystic kidney (ADPKD) is highly prevalent genetic disease. Liver cyst disease is the most common extrarenal manifestation in ADPKD and accounts for up to 10% of ADPKD morbidity and mortality. The clinical features of ADPKD liver disease arise from dramatic increases in liver cyst volumes.

Improved survival in metastatic colorectal cancer is associated with adoption of hepatic resection and improved chemotherapy.

Purpose: Fluorouracil/leucovorin as the sole therapy for metastatic colorectal cancer (CRC) provides an overall survival of 8 to 12 months. With an increase in surgical resections of metastatic disease and development of new chemotherapies, indirect evidence suggests that outcomes for patients are improving in the general population, although the incremental gain has not yet been quantified.

Methods: We performed a retrospective review of patients newly diagnosed with metastatic CRC treated at two academic centers from 1990 through 2006.