Biomedical subjects

Bryan A Whitson

Publications and source records attributed to Bryan A Whitson.

10 recordsLinked to original sources

PubMed2007

Trends in the treatment and outcome of pancreatic cancer in the United States.

BACKGROUND: Although pancreatic cancer is the fourth leading cause of cancer death, few studies have evaluated population-based trends in diagnosis, management, and outcome. METHODS: We used the Surveillance, Epidemiology, and End Results (SEER) registry to evaluate treatment trends and outcomes for patients 18 or older with pancreatic adenocarcinoma diagnosed from 1988 through 2002. RESULTS: We identified 38,073 patients diagnosed with pancreatic cancer over this 15-year period; the age-adjusted incidence did not change over this period. Most patients were diagnosed with metastatic disease (50.3%), few of whom underwent irradiation or cancer-directed surgery (CDS). For patients with localized or regional disease (32.9%), 53% underwent some form of treatment. Importantly, the rate of CDS increased from 19% in 1988 to 35% in 2002 (P < 0.0001). In multivariate analysis, young age, married status, and localized disease were associated with significantly higher CDS rates. For patients with nonmetastatic disease, 2-year survival rate increased from 8% in 1988 to 15% in 2000. For patients with non-metastatic cancer who survived at least 3 months, CDS was associated with a significantly higher 2-year survival rate (CDS, 36%; non-CDS, 10%). CONCLUSIONS: Most patients with pancreatic cancer, even at the end of our 15-year study period, still presented with metastatic disease, and the survival rate for such patients did not change in a meaningful way over time. The proportion of patients with nonmetastatic pancreatic cancer who underwent potentially curative surgery increased over time in the U.S.; the 2-year survival rate for such patients improved, but remained poor.

Age Factors↗

PubMed2006

Technology-enhanced interactive surgical education.

BACKGROUND: Our goal was to create surgical resident centered, interactive teaching modules rich in basic science and clinical content directly pertinent to patient care and surgical techniques that would facilitate education in the 80-h work week environment. METHODS: A systematic evaluation of available instructional tools determined that a technology-enhanced approach can effectively and efficiently address the new requirements for resident learning. An extensive evaluation of available technology determined the technology best suited to teaching the adult surgical learner. RESULTS: An on-line, multimedia-based surgical education environment using WebCT Vista (WebCT, Inc., Lynnfield, MA) and Macromedia Breeze (Adobe Systems, Inc., San Jose, CA) software packages was implemented. The concept was constructed on tenets of adult learning theory and based on the APDS curriculum and ACGME core competencies. WebCT Vista serves as virtual scaffolding, and Macromedia Breeze functions to deliver content rich multimedia audio and visual presentations. Core subdiscipline teaching modules were created, comprised of individual lecture packets developed by faculty. Components for testing pre/post module knowledge, feedback and evaluations are built-in. The online nature allows for 24-h access at locations that are convenient to the resident. CONCLUSIONS: Teaching modules enable maximal trainee and instructor flexibility, which translates into optimal adult learning and teaching. Lecture packets can be conveyed to all residents with unlimited availability in the virtual domain. Further refinement and continued implementation will help fill the void in direct didactic teaching left by mandated work hour restrictions, allowing for more efficient learning and teaching. There is great potential for broad application of the concept and technology to other training programs.

Adult↗

PubMed2006

Repression of cap-dependent translation attenuates the transformed phenotype in non-small cell lung cancer both in vitro and in vivo.

Aberrant hyperactivation of the cap-dependent protein synthesis apparatus has been documented in a wide range of solid tumors, including epithelial carcinomas, but causal linkage has only been established in breast carcinoma. In this report, we sought to determine if targeted disruption of deregulated cap-dependent translation abrogates tumorigenicity and enhances cell death in non-small cell lung cancer (NSCLC). NSCLC cell lines were stably transfected with either wild-type 4E-BP1 (HA-4E-BP1) or the dominant-active mutant 4E-BP1(A37/A46) (HA-TTAA). Transfected NSCLC cells with enhanced translational repression showed pronounced cell death following treatment with gemcitabine. In addition, transfected HA-TTAA and HA-4E-BP1wt proteins suppressed growth in a cloning efficiency assay. NSCLC cells transduced with HA-TTAA also show decreased tumorigenicity in xenograft models. Xenograft tumors expressing HA-TTAA were significantly smaller than control tumors. This work shows that hyperactivation of the translational machinery is necessary for maintenance of the malignant phenotype in NSCLC, identifies the molecular strategy used to activate translation, and supports the development of lung cancer therapies that directly target the cap-dependent translation initiation complex.

Adaptor Proteins, Signal Transducing↗

PubMed2006

Effects of insulin-like growth factor-1 receptor inhibition in mesothelioma. Thoracic Surgery Directors Association Resident Research Award.

BACKGROUND: Malignant mesothelioma is a devastating disease with a poor prognosis. Recent data have shown that insulin-like growth factor-1 receptor (IGF-1R) may play a role in oncogenic signaling. Our aim was to evaluate the effect of a novel IGF-1R inhibitor, NVP-AEW541, on cell growth and IGF associated pathways. METHODS: Malignant mesothelioma cell lines, H2373 and H2461, previously shown to activate the IGF pathway were grown in culture. The adherent cells, initially plated at 5 x 10(5) cells/plate, were treated for 72 hours, in triplicate, with varying concentration of NVP-AEW541 (0, 1, 5, 10, 20, and 50 microM). Viable cells were counted every 24 hours. Additionally, separate cultures in serum-free medium were treated with NVP-AEW541, then stimulated with IGF and lysates collected for immunoblot analysis. RESULTS: In both cell lines, 0, 1, 5, and 10 microM showed an inhibitory or static effect, while 20 and 50 microM were cidal. Immunoblot analysis demonstrated that phosphorylation of IGF-1R was inhibited by NVP-AEW541 at higher concentration. Phosphorylation of mitogen-activated protein kinase and Akt, downstream IGF pathway mediators, were also shown to be repressed by drug treatment. CONCLUSIONS: NVP-AEW541 has a concentration-dependent inhibitory effect on mesothelioma cells in culture. NVP-AEW541 acts by inhibition of IGF-1R phosphorylation. Inhibition effects phosphorylation of downstream mediators in a dose-dependent fashion. Inhibition of the IGF pathway decreases viability of mesothelioma cell culture. Further evaluation of NVP-AEW541, and other selective IGF-1R inhibitors, may play an important role in multimodal treatment of malignant mesothelioma.

Antineoplastic Agents↗

PubMed2006

Wedge gastroplasty and reinforced crural repair: important components of laparoscopic giant or recurrent hiatal hernia repair.

OBJECTIVE: Laparoscopic repair of a giant hiatal hernia (>50% of the stomach above the diaphragm) is associated with short-term recurrence rates of 12% to 42%. Recurrent hiatal hernias often have significantly altered anatomy, making laparoscopic repair challenging. We hypothesized that increasing intra-abdominal esophageal length by means of Collis wedge gastroplasty, complete fat-pad dissection, hernia-sac excision, and primary reinforced crural repair would minimize short-term recurrence and provide adequate symptomatic relief. METHODS: From January 1, 2001, though May 1, 2005, 61 patients underwent laparoscopic repair of a giant or recurrent hiatal hernia with a Collis wedge gastroplasty and Nissen fundoplication. Symptomatic outcomes were assessed with a validated questionnaire (Gastroesophageal Reflux Disease Health-Related Quality of Life). We obtained postoperative radiographic imaging to objectively assess anatomic results at a median of 1.13 years. RESULTS: Of the 61 patients, 12 (20%) were referred to our institution after previous repairs. Operating time averaged 308 +/- 103 minutes. The median hospital stay was 4 days. Postoperative complications occurred in 5 (8.2%) patients. One (1.6%) patient died of cardiac complications. Postoperatively, 52 (85%) patients completed the questionnaire with mean a Gastroesophageal Reflux Disease Health-Related Quality of Life questionnaire score of 1.15 +/- 2.78 (scale, 0-45; 0 = asymptomatic). Overall, 51 (98%) of the 52 respondents were satisfied with their surgical outcome. Postoperative radiographic data were available for 54 (89%) patients. We identified no recurrences at 1-month follow-up, and only 4.7% (2/42) had evidence of radiographic recurrence at 1 year or more. CONCLUSIONS: Consistent use of a Collis wedge gastroplasty with reinforced crural repair minimizes short-term recurrence after minimally invasive giant hiatal hernia repair. Symptomatic results are excellent in most patients.

Diaphragm↗

PubMed2005

Risk factors for primary graft dysfunction after lung transplantation.

OBJECTIVE: The International Society for Heart and Lung Transplantation has proposed a new grading system for primary graft dysfunction based on the ratio of arterial oxygen to fraction of inspired oxygen measured within 48 hours after lung transplantation. Worsening primary graft dysfunction grade is associated with increased operative mortality rates and decreased long-term survival. This study evaluated donor and recipient risk factors for postoperative International Society for Heart and Lung Transplantation grade 3 primary graft dysfunction. METHODS: We reviewed donor and recipient medical records of 402 consecutive lung transplantations performed between 1992 and 2004. We calculated a worst International Society for Heart and Lung Transplantation primary graft dysfunction grade in the first 48 hours postoperatively. Severe primary graft dysfunction (International Society for Heart and Lung Transplantation grade 3) was defined by a ratio of arterial oxygen to fraction of inspired oxygen of less than 200. Associations of potential risk factors with grade 3 primary graft dysfunction in the first 48 hours postoperatively were examined through bivariate and multivariate analysis. RESULTS: The 90-day mortality rate associated with the development of International Society for Heart and Lung Transplantation grade 3 primary graft dysfunction in the first 48 hours postoperatively was 17% versus 9% in the group without grade 3 primary graft dysfunction. Significant bivariate risk factors associated with this end point were increasing donor age, donor smoking history of more than 10 pack-years, early transplantation era (1992-1998), increasing preoperative recipient pulmonary artery pressure, and recipient diagnosis. In the multivariate analysis only recipient pulmonary artery pressure, donor age, and transplantation era were associated with grade 3 primary graft dysfunction in the first 48 hours postoperatively at a P value of less than .05. CONCLUSIONS: Our analysis of donor and recipient risk factors for severe primary graft dysfunction identified patient groups at high risk for poor outcomes after lung transplantation that might benefit from treatments aimed at reducing reperfusion injury.

Adolescent↗

PubMed2005

Molecular pathways in malignant pleural mesothelioma.

Malignant pleural mesothelioma, although uncommon, is highly lethal. There is a high correlation between associated environmental exposure factors, carcinogens, and its development. Carcinogenesis is also mediated by genetic defects that result in loss of tumor suppressors or over expression of proto-oncogenes. Factors such as the loss of CDK inhibition function, IGF stimulatory pathways, p14(ARF), p15(INK4b), p16(INK4a), p21, and p53 loss or mutation, VEGF and COX over expression are discussed. Correlations to potential therapeutic modalities are made.

Cell Transformation, Neoplastic↗

PubMed2005

Laparoscopic resection of periaortic paragangliomas.

Paragangliomas are extra-adrenal pheochromocytomas that are often located in the retroperitoneum along the aorta. Although laparoscopic resection is recommended for adrenal pheochromocytomas, few laparoscopic resections for paragangliomas have been reported. We describe the presentation and imaging findings of four patients with periarotic paraganglioma. Laparoscopic resection was successfully performed in three of the four patients; the fourth patient required conversion to an open procedure. This report adds to a growing number of cases documenting that laparoscopic resection of paragangliomas is safe and feasible.

Adult↗

PubMedDate not supplied

Pulmonary embolism associated with a vacuum-induced arm compartment syndrome: a setting for increased vigilance.

Vacuum injuries, otherwise known as negative pressure injuries, are unique mechanisms of traumatic injury. There are few reports of this mechanism in the literature and, although rare, familiarity with the presentation and management is essential to be life and limb saving. In addition, because of the severe inflammatory process, the potential is increased for life-threatening thrombosis and embolism. This is a case of a circumferential vacuum injury to the arm requiring fasciotomy complicated by development of pulmonary embolism. We describe treatment, postoperative management and a review of the relevant literature.

Adolescent↗

PubMedDate not supplied

Cardiopulmonary bypass in revascularization and fluid management of exercise-induced acute myocardial infarction.

A 52-year-old man was resuscitated from a cardiac arrest during a marathon run. During initial evaluation, he received a significant amount of crystalloid fluid to maintain end-organ perfusion. Based on electrocardiogram findings, myocardial infarction was suspected and an angiogram was performed. An acute thrombosis of the left anterior descending vessel was noted, angioplastied, and stented. Given that he was in cardiogenic shock, acidotic, and hemodynamically labile, an emergent coronary artery bypass grafting with cardiopulmonary bypass was performed to simultaneously revascularize the myocardium and remove intravascular fluid.

Angioplasty, Balloon, Coronary↗