Evaluation of three-dimensional computed tomography processing for deep inferior epigastric perforator flap breast reconstruction.

BACKGROUND: The deep inferior epigastric perforator flap procedure has become a popular alternative for women who require breast reconstruction. One of the difficulties with this procedure is identifying perforator arteries large enough to ensure that the harvested tissue is well vascularized. Current techniques involve imaging the perforator arteries with computed tomography (CT) to produce a grid mapping the locations of the perforator arteries relative to the umbilicus. OBJECTIVES: To compare the time it takes to produce a map of the perforators using either two-dimensional (2D) or three-dimensional (3D) CT, and to see whether there is a benefit in using a 3D model. METHODS: Patient CT abdomen and pelvis scans were acquired from a GE 64-slice scanner. CT image processing was performed with the GE 3D Advantage Workstation v4.2 software. Maps of the perforators were generated both as 2D and 3D representations. Perforators within a region 5 cm rostral and 7 cm caudal to the umbilicus were measured and the times to perform these measurements using both 2D and 3D images were recorded by a stopwatch. RESULTS: Although the 3D method took longer than the 2D method (mean [+/- SD] time 1:51+/-0:35 min versus 1:08+/-0:16 min per perforator artery, respectively), producing a 3D image provides much more information than the 2D images alone. Additionally, an actual-sized 3D image can be printed out, removing the need to make measurements and producing a grid. CONCLUSIONS: Although it took less time to create a grid of the perforators using 2D axial CT scans, the 3D reconstruction of the abdomen allows the plastic surgeons to better visualize the patient's anatomy and has definite clinical utility.

COX-2 inhibition results in alterations in nuclear factor (NF)-kappaB activation but not cytokine production in acute pancreatitis.

Acute pancreatitis is characterized by local inflammation and cytokine production, and release is thought to contribute to this process. Nuclear factor (NF)-kappaB activation and cytokine production are linked and inhibition of NF-kappaB has been shown to decrease the severity of pancreatitis. We have shown that inhibition of COX-2 ameliorates pancreatitis; however, the mechanism by which this effect occurs is unclear. Swiss Webster mice were injected intraperitoneally with either saline (control) or caerulein (CAE; 50 mg/kg) hourly for 8 hours; mice receiving CAE were further subdivided to receive saline or the cyclooxygenase-2 (COX-2) selective inhibitor (SC-58125; 10 mg, intraperitoneally) at the time of the first injection of CAE. Pancreata were harvested, histologic sections were scored, and protein was extracted to determine cytokine (interleukin [IL]-6, IL-1beta) levels and NF-kappaB subunits by ELISA and NF-kappaB activation by gel shift. In addition, serum was collected for measurement of cytokines. COX-2 inhibition resulted in decreased inflammation and a decrease in NF-kappaB activation. IL-6 and IL-1beta levels after COX-2 inhibition, however, remained elevated to levels equivalent to those of mice with histologic inflammation after CAE alone. COX-2 inhibition decreases inflammation as well as late-phase NF-kappaB activation but does not diminish levels of inflammatory cytokines, thus suggesting a two-phase activator of NF-kappaB. The attenuation of inflammation, despite unaltered cytokine levels, suggests that cytokines may not be critical for the inflammatory phase of pancreatitis.

The PPARgamma ligand, 15d-PGJ2, attenuates the severity of cerulein-induced acute pancreatitis.

INTRODUCTION: The prostaglandin D2 metabolite, 15d-PGJ2, a potent natural ligand for peroxisome proliferator-activated receptor gamma (PPARgamma), exerts antiinflammatory effects by inhibiting the induction of inflammatory response genes and NF-kappaB-dependent transcription. AIM To determine whether 15d-PGJ2 decreases the severity of secretagogue-induced acute pancreatitis (AP) and to assess cellular mechanisms contributing to these effects. METHODOLOGY Swiss Webster mice were injected with either saline or cerulein (50 microg/kg) hourly for 8 hours and received either 15d-PGJ2 (2 mg/kg) or vehicle 1 hour before and 4 hours after induction of AP. RESULTS Treatment with 15d-PGJ2 significantly attenuated AP, as determined by histologic assessment of edema, vacuolization, inflammation, and necrosis. This attenuation was associated with decreased cyclooxygenase-2 (COX-2) and intercellular adhesion molecule-1 (ICAM-1) expression and decreased serum and pancreatic IL-6 levels. Treatment with 15d-PGJ2 markedly inhibited NF-kappaB DNA-binding activity, and, moreover, this decreased activity was associated with a concomitant inhibition of IkappaB protein degradation. CONCLUSION Our findings demonstrate that 15d-PGJ2 attenuates the severity of AP most likely through the inhibition of COX-2 expression, IL-6 production, and NF-kappaB activation. Ligands specific for PPARgamma may represent novel and effective means of clinical therapy for AP.

Cyclooxygenase-2 gene disruption attenuates the severity of acute pancreatitis and pancreatitis-associated lung injury.

BACKGROUND & AIMS: Cyclooxygenase (COX) catalyzes the rate-limiting step in prostaglandin production; the inducible isoform, COX-2, has been implicated in a variety of inflammatory processes. The role of COX in acute pancreatitis and pancreatitis-associated lung injury is not known. METHODS: Acute pancreatitis was induced in Swiss Webster mice or mice deficient in the COX-2 (Ptgs2) or the COX-1 (Ptgs1) genes. Pancreata and lungs were harvested, and histologic sections of these tissues were scored. COX-2 expression, myeloperoxidase activity (a measurement of neutrophil sequestration), and serum amylase levels were determined. RESULTS: Acute pancreatitis was associated with induction of COX-2 expression. Treatment with NS-398 (a COX-2 inhibitor) significantly decreased the severity of pancreatitis. Furthermore, Ptgs2-deficient mice showed minimal histologic evidence of pancreatitis, a marked attenuation in the severity of lung injury, and a significant reduction in myeloperoxidase activity. In contrast, Ptgs1-deficient mice had pancreatitis and pulmonary inflammation, which was as severe or, in some instances, more severe than in the wild-type mice. CONCLUSIONS: Inhibition of COX-2 by either pharmacologic inhibition or selective genetic deletion markedly attenuated the severity of acute pancreatitis. Our findings identify the COX-2 isoform as an important regulator of the severity of acute pancreatitis and pancreatitis-associated lung injury.

Selective inhibition of NF-kappaB attenuates the severity of cerulein-induced acute pancreatitis.

BACKGROUND: Acute pancreatitis (AP) is associated with increased cytokine production, which can ultimately produce deleterious local and systemic effects. The transcription factor NF-kappaB is activated by degradation of its inhibitory factor, IkappaB, and can stimulate various cytokines. The purpose of this study was to determine whether the inhibition of NF-kappaB binding activity with a novel peptide that binds to the NF-kappaB essential modifier binding domain (NBD) could attenuate the severity of AP. STUDY DESIGN: AP was induced in Swiss Webster mice by hourly injections of the cholecystokinin analogue cerulein (50 microg/kg). Mice were injected with either the wild-type or control (mutated) NBD peptide at the time of the first cerulein injection; they were then sacrificed over a time course, and pancreata and lungs were harvested for histologic analysis and scoring. Myeloperoxidase activity was measured to assess neutrophil sequestration as an indicator of inflammation. NF-kappaB binding activity and steady-state levels of IkappaB and NF-kappaB subunits were determined by gel shift and Western blot, respectively. RESULTS: AP resulted in increased NF-kappaB DNA-binding activity and decreased steady-state levels of IkappaB. Treatment with NBD peptide decreased inflammation in the pancreas, decreased hemorrhage in the lungs, and decreased myeloperoxidase activity in both pancreas and lung. CONCLUSIONS: The marked induction of NF-kappaB binding activity suggests a role for this transcription factor in the early inflammatory changes associated with AP. Treatment with the NBD peptide attenuated the severity of injury associated with AP. Novel compounds that selectively target NF-kappaB may prove to be useful treatment of AP and AP-associated lung injury.

Peroxisome proliferator-activated receptor gamma ligand inhibits cell growth and invasion of human pancreatic cancer cells.

BACKGROUND: Peroxisome proliferator-activated receptor gamma (PPARgamma) is expressed in certain human cancers; ligand-induced PPARgamma activation can result in growth inhibition and differentiation in these cells. However, the precise mechanism for the antiproliferative effect of PPARgamma ligands is not entirely known. AIM OF STUDY: The purpose of this study was to examine the effect of PPARgamma ligands on pancreatic cancer cell growth and invasiveness. METHODS: The effect of two PPARgamma ligands, 15 deoxy-delta12,14 prostaglandin J2 (15d-PGJ2) and ciglitazone, on the growth of four human pancreatic cancer cell lines (BxPC-3, MIA PaCa-2, Panc-1, and L3.6) was assessed. Expression of cell-cycle and apoptotic-related proteins was measured. Finally, the effect of 15d-PGJ2 on pancreatic cancer cell invasiveness and matrix metalloproteinase expression was determined. RESULTS: Both 15d-PGJ2 and ciglitazone inhibited the growth of all four pancreatic cancer cell lines in a dose- and time-dependent fashion. Treatment of BxPC-3 cells with 15d-PGJ2 resulted in a time-dependent decrease in cyclin D1 expression associated with a concomitant induction of p21waf1 and p27kip1. In addition, 15d-PGJ2 treatment induced apoptosis through activation of caspase-8, -9, and -3. Moreover, pancreatic cancer cell invasiveness was significantly suppressed after treatment with a nontoxic dose of 15d-PGJ2, which was associated with a reduction of MMP-2 and MMP-9 protein levels and activity. CONCLUSIONS: These results demonstrate that PPARgamma ligands have the dual advantage of inhibiting pancreatic cancer cell growth while reducing the invasiveness of the tumor cells, suggesting a potential role for these agents in the adjuvant treatment of pancreatic cancer.