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W Scott Helton

Publications and source records attributed to W Scott Helton.

27 records · Page 2Linked to original sources
PubMed2002

The role of pancreatoscopy in the preoperative evaluation of intraductal papillary mucinous tumor of the pancreas.

BACKGROUND: Intraductal papillary mucinous tumor of the pancreas is a rare neoplasm managed by operative resection of the affected segment of the pancreas. GOALS: To evaluate the role of peroral pancreatoscopy in the diagnosis and preoperative localization of the affected region of the pancreatic duct and to undertake the appropriate operation for each patient. STUDY: Five patients with suspected intraductal papillary mucinous tumor of the pancreas were studied using endoscopic retrograde cholangiopancreatography, computed tomography of the abdomen, endoscopic ultrasonography, and peroral pancreatoscopy. The findings from these studies were compared, and operative resection was performed in each patient based on pancreatoscopic findings. RESULTS: Of the five patients with suspected intraductal papillary mucinous tumor, only four had histologically confirmed tumor, and the remaining one patient had a retention cyst of the pancreas. Pancreatoscopy correctly identified all four patients with the tumor while excluding the diagnosis of papillary tumor in one. CONCLUSION: Peroral pancreatoscopy is valuable in the preoperative evaluation of intraductal papillary mucinous tumor of the pancreas, especially in the localization of such tumor.

Adenocarcinoma, Papillary↗
PubMedDate not supplied

1990-2001 US general surgery chief resident gastric surgery operative experience: analysis of paradigm shift.

The almost complete disappearance of benign gastric ulcer disease has led to the perception that there may be an insufficient gastric surgery experience for surgery residents. This study analyzed resident-reported gastric procedure experience by chief residents from U.S. programs. The Resident Statistic Summaries (Report C) for 1990-2001 were compiled and analyzed. Results are expressed as the average number of operations performed per resident, standard deviation (SD), and the percentage (%) of total gastric operative cases. For all gastric-related surgery, the average reported cases per chief resident ranged from 9.8-12.4 with a peak in 1990 and a nadir in 1999; in 2001 the reported case average was 11.3 (SD ranged from 6-8). Over the same interval, vagotomy decreased from 24% in 1990 to 7% in 2001, whereas gastric-reduction operations increased from 5%-34%. Total gastrectomy remained a constant less than 1.0 per chief resident (range 0.6-0.8), whereas partial gastric resection (PGR) was unchanged. The percentage of all types of gastric resections slightly diminished from 34% in 1990 to 29% in 2001. U.S. surgical chief residents report a widely variable experience in gastric surgery over the period analyzed. However, their overall experience has not significantly diminished since 1990 although specific procedural volume has varied.

Digestive System Surgical Procedures↗
PubMedDate not supplied

Eicosapentaenoic acid supplementation reduces tumor volume and attenuates cachexia in a rat model of progressive non-metastasizing malignancy.

BACKGROUND: Eicosapentaenoic acid (EPA) has been shown to have anti-inflammatory and tumor growth inhibitory effects clinically and experimentally; evidence also supports the role of EPA in attenuating cancer-associated weight loss, but the mechanisms of these effects remain to be defined. As the liver plays a central role in modulating nutritional status and the cachexia syndrome, we examined the liver and nutritional parameters indicative of cachexia along with the tumor volume in response to oral EPA supplementation in a rat model of progressive non-metastasizing malignancy. METHODS: Fischer 344 rats implanted with the methylcholanthrene-induced fibrosarcoma (MCA) were trained to meal-feed with access to food from 8:00 PM to 8:00 AM and water ad libitum. On day 13, rats were randomly divided into 3 study groups: (1) 5.0 g/kg per day EPA plus 10 IU vitamin E/g fat, (2) 5.0 g/kg per day corn oil plus 10 IU vitamin E/g fat, and (3) 5.0 g/kg per day saline plus 10 IU vitamin E/g saline. The treatment was delivered via oral gavage twice daily. The animals were killed on day 29, and serum plus tissues (ie, liver and lung) were collected and frozen for analysis. Parameters evaluated include the following: tumor volume, weight loss, liver weight, total liver protein, liver lipid content, serum albumin content, and macrophage inflammatory protein-2 (MIP-2) levels. RESULTS: EPA-treated rats showed a reduction in tumor volume compared with corn oil (25% reduction, p < .01) and saline (33% reduction, p < .01) animals. EPA rats also demonstrated increased liver weight (p < .01) and total liver protein levels (p < .03) over saline-treated animals. EPA- and corn oil-treated rats received more calories than the saline group because of the dietary fat treatments (p < .01) and had elevated lipid content in their livers (p = .05 and p = .04, respectively) compared with saline rats. Serum albumin (a marker of liver function) and MIP-2 levels (a marker of the hepatic acute phase response) were not different between treatment groups. CONCLUSIONS: EPA supplementation resulted in a dramatic reduction of tumor volume and mild improvements in weight maintenance. In addition, EPA-treated animals demonstrated increased total liver protein and serum protein levels. Regression analyses showed that the weight and protein differences between treatment groups were not correlated with individual tumor volumes. The increase in liver and serum protein was not explained by differences in albumin or MIP-2. We conclude that the tumor growth inhibitory effects and anticachexiogenic effects of EPA are independent phenomena, and the effects on cachexia may be related to increased levels of undefined protein(s) in the liver and serum. To our knowledge, this is the first study to demonstrate the effects of EPA in the MCA fibrosarcoma model and is also novel in its evaluation of EPA as an anticachexiogenic therapy in progressive non-metastasizing malignancy. Further studies may identify the protein(s) elevated in the liver and the mechanisms for the development of EPA nutritional therapies for the treatment of progressive malignancies.

Administration, Oral↗
PubMedDate not supplied

Modulation of the ubiquitin-proteasome proteolytic pathway by eicosapentaenoic acid supplementation in a model of progressive malignancy.

BACKGROUND: A benefit for eicosapentaenoic acid (EPA) supplementation for protein maintenance in cancer patients exists, although specific mechanisms are unknown. As the ubiquitin-proteasome proteolytic (UPP) pathway has been implicated in protein use in malignancy, we determined mRNA levels for UPP components in the liver and muscles from EPA-treated rats bearing the methylcholanthrene (MCA) fibrosarcoma. METHODS: Rats implanted with MCA tumor were divided into 3 groups on day 13: EPA (5 g/kg per day plus 10 IU vitamin E/g fat), corn oil (5 g/kg per day plus 10 IU vitamin E/g fat), and saline (5 g/kg per day plus 10 IU E/g saline). On day 29, tumor volume (TV) was determined; liver and quadriceps muscles were also excised to determine gene expression of C2, C3, E2(14k), and E3alpha by reverse transcription-polymerase chain reaction (RT-PCR). RESULTS: EPA-treated rats demonstrated a reduced TV of 21% compared with the 28% and 30% TV of corn oil- and saline-treated rats, respectively. Muscle mRNA levels of E2(14k) and E3alpha in EPA-treated animals were decreased compared with corn oil- and saline-treated animals. EPA treatment also decreased hepatic C2, C3, and E2(14k) mRNA levels compared with saline treatment. CONCLUSION: EPA supplement decreased skeletal muscle E2(14k), E3alpha, and hepatic C2 mRNA levels compared with the isocaloric, isonitrogenous corn oil supplement, supporting a treatment-specific effect. The decrease in hepatic C3 and E2(14k) mRNA levels induced by EPA were partly because of caloric benefit and partly attributable to a treatment-specific effect. Additionally, differences in the hepatic and muscle gene expressions of UPP components suggested an organ-specific effect for omega-3 fatty acid activity.

Animals↗
PubMedDate not supplied

Inhibition of activator protein-1 transcription factor activation by omega-3 fatty acid modulation of mitogen-activated protein kinase signaling kinases.

BACKGROUND: Lipopolysaccharide (LPS)-stimulated macrophages (Mphi) produce excess tumor necrosis factor (TNF), and the direct inhibition of IkappaB phosphorylation and its subsequent separation from the nuclear factor kappaB (NFkappaB)-IkappaB complex has been experimentally supported as a mechanism for omega-3 fatty acid (FA) inhibition of this TNF response. However, TNF production is a "late" event in the LPS-induced Mpsi inflammatory cascade, and in addition to NFkappaB-associated pathways, a separate transcription factor, activator protein-1 (AP-1) is an important pathway for Mpsi proinflammatory cytokine production. The mitogen-activated protein kinase (MAPK) cascade regulates both NFkappaB-IkappaB--and AP-1-associated gene transcription through several cross-amplifying phosphorylation kinases, specifically p44/42 [ie, extracellular signal-regulated kinase (ERK) 1/2], p38, and c//jun N-terminal kinase (JNK)/stress-activated protein kinase (SAPK). The activation of these kinases occurs in the proximal MAPK cascade and activation modulates AP-1 activation. In this set of experiments, it was hypothesized that inhibition of MAPK signaling phosphorylation kinases by omega-3 fatty acids in a model of LPS-stimulated Mphi(s) would alter the activation of the proinflammatory cytokine transcription factor AP-1. METHODS: RAW 264.7 cells were pretreated with a sterile, commercially available, pharmaceutical grade omega-3 FA emulsion, equivalent grade omega-6 FA emulsion, or Dulbecco's modified eagles medium (media alone) for 4 hours. Cells were washed twice and exposed to LPS for 15 minutes. Total cell lysates were collected, and both total and phosphorylated portions of the p44/42, p38, and JNK/SAPK proteins were determined by Western blotting. AP-1 nuclear translocation was determined by electromobility shift assay. RESULTS: Phosphorylation of p44/42 and JNK/SAPK proteins of the MAPK pathways in LPS-stimulated Mpsi(s) was significantly reduced by omega-3 FA treatment compared with Mphi treated with omega-6 FA or media alone. In contrast, phosphorylation of p38 was not inhibited in the presence of omega-3 or (omega-6 FA treatment compared with media alone. Omega-3 FA pretreatment inhibited AP-1 activation. CONCLUSIONS: omega-3 FA inhibited p44/42 and JNK/SAPK phosphorylation; however, p38 remained unchanged. Phosphorylation of p44/42 and JNK/SAPK are the immediate prior steps in AP-1 activation. Attenuated AP-1 activation and subsequent attenuated gene-level proinflammatory cytokine elaboration is anticipated after inhibition of these MAPK intermediates and is confirmed by the reduction in AP-1 activity. These results provide further evidence for the transcriptional level regulation in the elaboration of proinflammatory cytokines by omega-3 FA in this Mphi model.

Cells, Cultured↗
PubMedDate not supplied

Synergistic anti-inflammatory activity of omega-3 lipid and rofecoxib pretreatment on macrophage proinflammatory cytokine production occurs via divergent NF-kappaB activation.

UNLABELLED: Omega-3 lipid pretreatment significantly decreases TNF-alpha production in LPS-stimulated Mphis; however, this response is only a partial inhibition, suggesting that other nonsubstrate- (lipid) dependent mechanisms are involved. The cyclooxygenase (COX)-2 enzyme is principally responsible for lipid metabolism; thus, a selective COX-2 inhibitor (Rofecoxib) would clarify if it is an omega-3 lipid direct effect or a COX-2 enzyme-associated modulated reduction in TNF-alpha. Moreover, potential synergy between omega-3 lipids and selective COX-2 inhibition is postulated. HYPOTHESIS: Through divergent regulatory mechanisms, omega-3 lipids in combination with Rofecoxib will synergistically decrease the LPS-stimulated Mphi inflammatory response. METHODS: RAW 264.7 cells were pretreated with omega-3 lipids, Rofecoxib, or combination treatment and then washed and exposed to LPS. Supernatants were collected for ELISA, total proteins were obtained to determine COX-2 protein expression by Western blot, and nuclear extracts were isolated to determine NF-kappaB activation by electromobility shift assay. RESULTS: TNF-alpha and PGE2 production was significantly decreased with omega-3 and Rofecoxib pretreatment, and with combination treatment a further decrease in TNF-alpha production was observed. COX-2 protein expression was demonstrated to increase in omega-3, Rofecoxib, and combination groups stimulated with LPS. No alteration in NF-kappaB activation was observed with Rofecoxib or combination pretreatment compared with LPS-stimulated control cells. Repletion of prostaglandin (PGE2) in the Mphi model significantly decreased TNF-alpha in all groups. CONCLUSIONS: Omega-3 lipids and Rofecoxib independently decrease TNF-alpha and PGE2 production in LPS-stimulated Mphi, yet in combination a synergistic reduction in TNF-alpha production is observed. Although the anti-inflammatory effects observed from omega-3 lipids are known to occur partially through decreasing NF-kappaB activation, we demonstrated that Rofecoxib or even a combination of omega-3 and Rofecoxib does not alter NF-kappaB activation, as seen with omega-3 lipids alone. These data support that combination treatment may result in decreased Mphi inflammation, yet this occurs via divergent mechanisms.

Animals↗
PubMedDate not supplied

A priori dietary omega-3 lipid supplementation results in local pancreatic macrophage and pulmonary inflammatory response attenuation in a model of experimental acute edematous pancreatitis (AEP).

BACKGROUND: Acute pancreatitis is often complicated by multiorgan dysfunction, which is postulated to occur in part by macrophage infiltration into the pancreas. Eicosapentaenoic acid (EPA), an omega-3 fatty acid, is the principal biologic component of fish oil and has clinically and experimentally been demonstrated to be anti-inflammatory. We hypothesized that dietary EPA supplementation before the induction of pancreatitis would attenuate both M-mediated local pancreatic and systemic pulmonary inflammatory response in an in vivo model of acute edematous pancreatitis (AEP). METHODS: Male Sprague-Dawley (SD) rats were pretreated 2 times per day with oral gavage with EPA (omega-3 fatty acid; 5 mg/kg/dose) or omega-6 fatty acid control (5 mg/kg/dose) or saline (equal volume) for 2 weeks. AEP was induced in omega-3, omega-6, and saline pretreated rats by 5 hourly subcutaneous (SC) injections of cerulein. Pancreas, lung, and serum were harvested 3 hours after the last cerulein injection. Severity of pancreatitis was confirmed by serum amylase and by histopathologic score. Pancreatic macrophage infiltration was assessed by confocal fluorescent microscopy, and pulmonary leukocyte respiratory burst (LRB) analysis was performed on mononuclear cells obtained from bronchioalveolar lavage (BAL). RESULTS: All animals demonstrated acute pancreatitis through hyperamylasemia and histopathologic examination. Confocal analysis demonstrated significantly lower macrophage infiltration, and BAL analysis by flow cytometry demonstrated significantly lower (p < .05) LRB in the omega-3-treated group compared with the omega-6 and the saline pancreatitis group. CONCLUSIONS: Attenuation of both pancreatic MPhi inflammatory response and pulmonary leukocyte respiratory burst in AEP by EPA supports further investigation into the potential role for EPA dietary supplementation in the progression of pancreatitis-associated sequelae.

Amylases↗