A novel pancreatic tumour and stellate cell 3D co-culture spheroid model.

BACKGROUND: Pancreatic ductal adenocarcinoma is a devastating disease with poor outcome, generally characterized by an excessive stroma component. The purpose of this study was to develop a simple and reproducible in vitro 3D-assay employing the main constituents of pancreatic ductal adenocarcinoma, namely pancreatic stellate and cancer cells. METHOD: A spheroid assay, directly co-culturing human pancreatic stellate cells with human pancreatic tumour cells in 3D was established and characterized by electron microscopy, immunohistochemistry and real-time RT-PCR. In order to facilitate the cell type-specific crosstalk analysis by real-time RT-PCR, we developed a novel in vitro 3D co-culture model, where the participating cell types were from different species, human and mouse, respectively. Using species-specific PCR primers, we were able to investigate the crosstalk between stromal and cancer cells without previous cell separation and sorting. RESULTS: We found clear evidence for mutual influence, such as increased proliferation and a shift towards a more mesenchymal phenotype in cancer cells and an activation of pancreatic stellate cells towards the myofibroblast phenotype. Using a heterospecies approach, which we coined virtual sorting, confirmed the findings we made initially in the human-human spheroids. CONCLUSIONS: We developed and characterized different easy to set up 3D models to investigate the crosstalk between cancer and stroma cells for pancreatic cancer.

Fibroblast drug scavenging increases intratumoural gemcitabine accumulation in murine pancreas cancer.

OBJECTIVE: Desmoplasia and hypovascularity are thought to impede drug delivery in pancreatic ductal adenocarcinoma (PDAC). However, stromal depletion approaches have failed to show clinical responses in patients. Here, we aimed to revisit the role of the tumour microenvironment as a physical barrier for gemcitabine delivery. DESIGN: Gemcitabine metabolites were analysed in LSL-KrasG12D/+ ; LSL-Trp53R172H/+ ; Pdx-1-Cre (KPC) murine tumours and matched liver metastases, primary tumour cell lines, cancer-associated fibroblasts (CAFs) and pancreatic stellate cells (PSCs) by liquid chromatography-mass spectrometry/mass spectrometry. Functional and preclinical experiments, as well as expression analysis of stromal markers and gemcitabine metabolism pathways were performed in murine and human specimen to investigate the preclinical implications and the mechanism of gemcitabine accumulation. RESULTS: Gemcitabine accumulation was significantly enhanced in fibroblast-rich tumours compared with liver metastases and normal liver. In vitro, significantly increased concentrations of activated 2',2'-difluorodeoxycytidine-5'-triphosphate (dFdCTP) and greatly reduced amounts of the inactive gemcitabine metabolite 2',2'-difluorodeoxyuridine were detected in PSCs and CAFs. Mechanistically, key metabolic enzymes involved in gemcitabine inactivation such as hydrolytic cytosolic 5'-nucleotidases (Nt5c1A, Nt5c3) were expressed at low levels in CAFs in vitro and in vivo, and recombinant expression of Nt5c1A resulted in decreased intracellular dFdCTP concentrations in vitro. Moreover, gemcitabine treatment in KPC mice reduced the number of liver metastases by >50%. CONCLUSIONS: Our findings suggest that fibroblast drug scavenging may contribute to the clinical failure of gemcitabine in desmoplastic PDAC. Metabolic targeting of CAFs may thus be a promising strategy to enhance the antiproliferative effects of gemcitabine.

The ageing pancreas: a systematic review of the evidence and analysis of the consequences.

Senior people constitute the fastest growing segment of the population. The elderly are at risk for malnutrition, thought to be caused by reduced food intake or involution of the physiological capacity of the GI tract. Age-related changes are well known in other secretory organs such as liver, kidney and intestine. The pancreas, representing a metabolically active organ with uptake and breakdown of essential nutritional components, changes its morphology and function with age. During childhood, the volume of the pancreas increases, reaching a plateau between 20 and 60 years, and declines thereafter. This decline involves the pancreatic parenchyma and is associated with decreased perfusion, fibrosis and atrophy. As a consequence of these changes, pancreatic exocrine function is impaired in healthy older individuals without any gastrointestinal disease. Five per cent of people older than 70 years and ten per cent older than 80 years have pancreatic exocrine insufficiency (PEI) with a faecal elastase-1 below 200 µg g-1 stool, and 5% have severe PEI with faecal elastase-1 below 100 µg g-1 stool. This may lead to maldigestion and malnutrition. Patients may have few symptoms, for example steatorrhoea, diarrhoea, abdominal pain and weight loss. Malnutrition consists of deficits of fat-soluble vitamins and is affecting both patients with PEI and the elderly. Secondary consequences may include decreased bone mineral density and results from impaired absorption of fat-soluble vitamin D due to impaired pancreatic exocrine function. The unanswered question is whether this age-related decrease in pancreatic function warrants therapy. Therapeutic intervention, which may consist of supplementation of pancreatic enzymes and/or vitamins in aged individuals with proven exocrine pancreas insufficiency, could contribute to healthy ageing.

Core content for venous and Lymphatic Medicine: 2022 revision.

The core content for a medical specialty outlines the scope of the discipline as well as the categories of knowledge considered essential to practice in the field. It provides a template for the development of curricula for medical school, graduate, and postgraduate education, as well as for creating certification standards. Venous and Lymphatic Medicine (VLM) is a specialty that has benefitted from contributions from specialists from several medical disciplines. Optimally, the societies, boards, and residency review committees representing these disciplines would uniformly recognize the scope of VLM to develop education and assessment standards to allow training and identification of qualified practitioners. In order to inform the standard setting bodies and other stakeholders of the current scope of VLM, a task force of VLM experts from cardiology, dermatology, emergency medicine, general surgery, interventional radiology, vascular medicine, and vascular surgery was formed to revise a 2014 consensus document defining the core content of the specialty of VLM.

Cationic liposomal paclitaxel plus gemcitabine or gemcitabine alone in patients with advanced pancreatic cancer: a randomized controlled phase II trial.

BACKGROUND: Paclitaxel embedded in cationic liposomes (EndoTAG™-1; ET) is an innovative agent targeting tumor endothelial cells. This randomized controlled phase II trial evaluated the safety and efficacy of ET in combination with gemcitabine (GEM) in advanced pancreatic cancer (PDAC). PATIENTS AND METHODS: Chemotherapy-naive patients with locally advanced or metastatic disease were randomly assigned to receive weekly GEM 1000 mg/m(2) or GEM plus twice-weekly ET 11, 22 or 44 mg/m(2) for 7 weeks. After a safety run-in of 100 patients, a second cohort continued treatment. End points included overall survival (OS), progression-free survival (PFS), tumor response and safety. RESULTS: Two hundred and twelve patients were randomly allocated to the study and 200 were treated (80% metastatic, 20% locally advanced). Adverse events were manageable and reversible. Transient thrombocytopenia and infusion reactions with chills and pyrexia mostly grade 1 or 2 occurred in the ET groups. Disease control rate after the first treatment cycle was 43% with GEM and 60%, 65% and 52% in the GEM + ET cohorts. Median PFS reached 2.7 compared with 4.1, 4.6 and 4.4 months, respectively. Median OS was 6.8 compared with 8.1, 8.7 and 9.3 months, respectively. CONCLUSIONS: Treatment of advanced PDAC with GEM + ET was generally well tolerated. GEM + ET showed beneficial survival and efficacy. A randomized phase III trial should confirm this positive trend.

Conservative Treatment of Chronic Pancreatitis: A Practical Approach.

BACKGROUND: Chronic pancreatitis is a long-standing, inflammatory condition of the pancreas that leads to the progressive damage and loss of function of pancreatic parenchyma and to the development of possible locoregional and systemic medical complications. MATERIALS AND METHODS: In this review, we tried to summarize the current evidence on non-surgical treatment trying to suggest a practical approach to the management of chronic pancreatitis. RESULTS: Besides the unclear pathophysiological mechanism and a poorly unknown epidemiology, chronic pancreatitis is a complex syndrome that displays different possible challenges for physicians. Despite being traditionally considered as a benign disease, chronic pancreatitis encompasses 10-year mortality rates which are superior to the ones reported for some of the most common cancers. CONCLUSIONS: Chronic pancreatitis encompasses the management of multiple and complex medical co-morbidities that needs to be understood and addressed in a multidisciplinary specialist context.

[Autoimmune pancreatitis]. / Autoimmune Pankreatitis.

Autoimmune pancreatitis has been established as a special entity of pancreatitis. It is an enigmatic disease since it is adding an autoimmune etiology to the existing causes of pancreatitis. Morphological hallmarks of the disease are narrowing of the pancreatic duct system and the bile duct by periductal lymphoplasmocytic inflammation. This results in many cases in obstructive jaundice due to a mass-forming lesion in the pancreatic head mimicking pancreatic ductal adenocarcinoma. Therefore, patients will frequently undergo surgery. Histopathologically, the disease can be diagnosed by IgG4-positive plasma cells. Serologically, patients may present with elevated serum IgG and IgG4 levels. Other autoantibodies are also described. Association with other autoimmune manifestations in a wide range of organs is frequent. Autoimmune pancreatitis will respond to steroid treatment, which is of specific importance because pancreatic cancer is one of its clinical differential diagnoses. It is important to positively diagnose autoimmune pancreatitis, especially if the bile ducts are affected, since cholangitis may be or become a prominent problem before or after surgery.

Endoscopic classification of the papilla of Vater. Results of an inter- and intraobserver agreement study.

BACKGROUND: Many endoscopists acknowledge that the appearance of the papilla of Vater seems to affect biliary cannulation. To assess the association between the macroscopic appearance of the papilla and biliary cannulation and other related clinical issues, a system is needed to define the appearance of the papilla. OBJECTIVE: The purpose of this study was to validate an endoscopic classification of the papilla of Vater by assessing the interobserver and intraobserver agreements among endoscopist with varying experience. METHODS: An endoscopic classification, based on pictures captured from 140 different papillae, containing four types of papillae was proposed. The four types are (a) Type 1: regular papilla, no distinctive features, 'classic appearance'; (b) Type 2: small papilla, often flat, with a diameter ≤ 3 mm (approximately 9 Fr); (c) Type 3: protruding or pendulous papilla, a papilla that is standing out, protruding or bulging into the duodenal lumen or sometimes hanging down, pendulous with the orifice oriented caudally; and (d) Type 4: creased or ridged papilla, where the ductal mucosa seems to extend distally, rather out of the papillary orifice, either on a ridge or in a crease. To assess the level of interobserver agreement, a web-based survey was sent out to 18 endoscopists, containing 50 sets of still images of the papilla, distributed between the four different types. Three months later a follow-up survey, with images from the first survey was sent to the same endoscopists. RESULTS: Interobserver agreement was substantial (κ = 0.62, 95% confidence interval (CI) 0.58-0.65) and were similar for both experts and non-experts. The intraobserver agreement assessed with the second survey was also substantial (κ = 0.66, 95% CI 0.59-0.72). CONCLUSION: The proposed endoscopic classification of the papilla of Vater seems to be easy to use, irrespective of the level of experience of the endoscopist. It carries a substantial inter- and intraobserver agreement and now the clinical relevance of the four different papilla types awaits to be determined.

Experimental model for repetitive ischemic attacks in the gerbil: the cumulative effect of repeated ischemic insults.

An experimental model for repeated ischemic attacks, which allows easy induction of cerebral ischemia of any desired duration and frequency, has been developed in the gerbil. With this procedure, a pronounced cumulative effect on development of edema and tissue injury was observed using 3 separate, 5-min bilateral occlusions of the common carotid arteries spaced at various time intervals. This effect was most evident when the occlusions were carried out at 1-h intervals, i.e., during the period of marked postischemic hypoperfusion. Such animals, killed after 24 h of recirculation, showed significantly more severe edema and brain tissue injury in the areas exposed to ischemia than was observed in animals killed 24 h after single 5- or 15-min occlusions. The changes of regional CBF, assayed with a [3H]nicotine method, indicated a relatively rapid onset of hypoperfusion of similar degree after each release of arterial occlusion. The hypoperfusion recovered significantly within 6 h of recirculation following either single or multiple occlusions, and no residual hypoperfusion was observed in animals which, when killed at 24 h, showed severe edema and brain tissue injury. This model should prove useful in elucidating the pathophysiological mechanisms operative in repetitive cerebral ischemia.

Global cerebral ischemia associated with cardiac arrest in the rat: I. Dynamics of early neuronal changes.

Light microscopic neuronal changes were studied in rats subjected to 10 min of global ischemia produced by compression of the major cardiac vessels. Observations of cresyl violet-stained sections revealed early changes involving predominantly GABAergic neurons in various locations. In rats killed 15 min after recirculation, the changes were characterized by the appearance of a clear peripheral zone with condensation of the remaining neuronal cytoplasm. After 1 h, these zones appeared to be compartmentalized into individual pearl-like vacuoles, especially prominent in the nucleus reticularis thalami. After 3 h, the cytoplasmic vacuoles disappeared and the neuronal changes, particularly in the cerebral cortex, striatum, hippocampus, and pars reticulata of the substantia nigra, consisted mainly of hyperchromasia or loss of Nissl substance. After 2 days, the cerebral cortex and thalamus contained occasional neurons with conspicuously large nucleoli. After 7 days, the hippocampus revealed an approximately 50% loss of CA1 pyramidal neurons, associated with intense microglial reactivity in the stratum radiatum, whereas the neuronal destruction was more complete in the nucleus reticularis thalami. Our observations suggest a possibility that early changes in GABAergic neurons may provide a period of neuronal disinhibition and thus contribute to an excitatory ischemic damage in regions connected by GABAergic circuitry.

Superficial thrombophlebitis diagnosed by duplex scanning.

Since July 1982, this noninvasive vascular laboratory has performed 12,856 lower extermity venous duplex examinations. All cases of acute venous thrombosis have been categorized and entered into a computer data base. One thousand four hundred twelve examinations were positive for acute venous thrombosis. This report analyzes the laboratory's entire experience with superficial thrombophlebitis (SVT). One hundred eighty-six patients were diagnosed by duplex scanning to have SVT. Women outnumbered men 99 to 87. They were slightly older (average age 58.4 +/- 16.2 years) compared with the men (53.8 +/- 14.2 years). Men were more likely to have a complicated course of SVT (40% vs 22%; p less than 0.01). Complications included either radiographically documented pulmonary embolism or deep venous involvement. Fifty-seven (31%) patients had at least one complication of SVT. A series of predisposing factors was analyzed and six factors were associated with an increased risk of complications. They are bilateral SVT (p less than 0.01), age greater than 60 years (p less than 0.01), male sex (p less than 0.01), history of deep venous thrombosis (p less than 0.01), bed rest (p less than 0.02), and presence of infection (p less than 0.02). Location of thrombus within the greater saphenous vein (35%) was most likely to be associated with complications. Isolated varicosities (8%) were least likely to be associated with complications. Duplex scanning identifies a significant number of complications of patients with SVT and should be obtained in cases of saphenous vein involvement or in the presence of associated risk factors.

Science and pseudoscience in the development of eye movement desensitization and reprocessing: implications for clinical psychology.

The enormous popularity recently achieved by Eye Movement Desensitization and Reprocessing (EMDR) as a treatment for anxiety disorders appears to have greatly outstripped the evidence for its efficacy from controlled research studies. The disparity raises disturbing questions concerning EMDR's aggressive commercial promotion and its rapid acceptance among practitioners. In this article, we: (1) summarize the evidence concerning EMDR's efficacy; (2) describe the dissemination and promotion of EMDR; (3) delineate the features of pseudoscience and explicate their relevance to EMDR; (4) describe the pseudoscientific marketing practices used to promote EMDR; (5) analyze factors contributing to the acceptance of EMDR by professional psychologists; and (6) discuss practical considerations for professional psychologists regarding the adoption of EMDR into professional practice. We argue that EMDR provides an excellent vehicle for illustrating the differences between scientific and pseudoscientific therapeutic techniques. Such distinctions are of critical importance for clinical psychologists who intend to base their practice on the best available research.

Does the asymptomatic limb harbor deep venous thrombosis?

Deep venous thrombosis (DVT) is a great masquerader that cannot be reliably predicted by a patient's symptoms, history, or risk factors. Bilateral lower extremity duplex ultrasonography scans were made of 2,511 patients and analyzed to identify, if possible, a population in which a unilateral study would be appropriate. A total of 1,086 (43%) patients were found to have deep venous thrombosis--742 (30%) unilateral and 344 (14%) bilateral. Of the patients with DVT for whom side-of-symptom information was recorded, 64% had symptoms referable to the involved extremity and 36% had symptoms referable to the contralateral extremity. Of the 362 patients who had asymptomatic lower extremities, 128 (35%) had DVT. Moreover, clots were found in asymptomatic limbs in an additional 263 patients whose contralateral limb was symptomatic. Logistic regression analysis did not reveal combinations of symptoms and risk factors that could predict DVT. If DVT is suspected, the patient should undergo bilateral lower extremity duplex scanning.

Allastair B. Karmody Award. Calf vein thrombi are not a benign finding.

BACKGROUND: Currently, there is no consensus in the literature regarding which patients with calf vein thrombi are at high risk for proximal propagation. This study examined patients with isolated calf vein thrombi with serial duplex scans in order to identify risk factors that would predict outcome. PATIENTS AND METHODS: Between May 1989 and November 1994, 288 patients were identified with isolated calf vein thrombi. One hundred ninety-two of them had sequential scans performed. RESULTS: Fifty-three (28%) of the 192 patients had propagation of their initial thrombi. The most proximal level of propagation was the popliteal vein in 11 patients, the superficial femoral vein in 5, the common femoral vein in 5, adjacent tibial or soleal veins in 24, adjacent soleal veins alone in 7, and the lesser saphenous vein in 1. Three patients whose thrombi propagated had free-floating thrombus tips in the large veins of their thighs. Symptoms, prophylaxis, and risk factor analysis comparing those patients whose thrombi propagated to those whose thrombi did not found no statistically significant prognostic value. Single or multiple calf vein thrombi did not predict propagation. Of the 23 patients treated with heparin, only 3 had thrombus propagation. None of these reached the level of the knee (including popliteal vein). CONCLUSIONS: The natural history of distal lower extremity thrombosis does not appear to be as benign as previously believed.

Operative management of greater saphenous thrombophlebitis involving the saphenofemoral junction.

Forty-three consecutive patients with greater saphenous vein (GSV) thrombosis extending to the saphenofemoral junction (SFJ) were treated. Twenty-three patients had extension of thrombus into the common femoral vein (CFV). Twenty patients had thrombus extending to but not within the CFV. Symptoms, risk factors, and physical examination were not predictive of CFV thrombus extension. When compared with the operative record, duplex scans accurately located the extent of the thrombosis 100% of the time. Forty-one surgical procedures were performed. No patients had pulmonary emboli during the procedures. Thirty-seven patients were treated as outpatients or were discharged within 3 days of their surgical procedures. The two patients who did not undergo operative procedures in this series had complete occlusion of the CFV with extension into the external iliac vein. Thrombus within 3 cm of the SFJ is an indication for surgical intervention. Disconnection of the GSV from the CFV prevents extension of the thrombus, and a limited CFV thrombectomy can be performed when necessary. This is considerably more cost-effective than treatment with anticoagulation.

Infection of endovascular stents in a swine model.

BACKGROUND: Percutaneous balloon angioplasty with intravascular metallic stent placement has rapidly gained popularity for the treatment of arterial occlusive disease. Although the incidence of vascular prosthetic infection is well described, the risk of infection following metallic stent placement is unknown. The purpose of this study was to determine if intravascular metallic stents could become infected following systemic bacterial challenge. METHODS: Balloon expandable metallic stents were implanted in the iliac arteries of 10 swine following balloon catheter angioplasty. A second angioplasty, without stent placement, was also performed in the contralateral iliac artery. A bacterial challenge with Staphylococcus aureus was then infused into the aorta immediately after stent placement. Group 1 (n = 5) was killed at 72 hours, and group 2 (n = 5) at 3 weeks. A third group (n = 5) underwent stent placement without bacterial challenge and was killed at 3 weeks. At the time of death, the stents were cultured, and both iliac arteries were submitted for pathologic examination. Arterial patency and evidence of systemic infection were also assessed. RESULTS: In the animals sacrificed at 72 hours (group 1), 80% had stent cultures with significant growth of S aureus; while at 3 weeks (group 2), 60% of cultures were positive. Of the stents placed without bacterial challenge (group 3), none had a positive culture at 3 weeks. In group 2, 40% of the stented arteries remained patent, while 100% of group 3 remained patent until sacrifice at 3 weeks. All of the stented arteries which were patent at 3 weeks were culture negative, while all those which were thrombosed were culture positive for S aureus. When compared to angioplasty alone, the presence of a stent was strongly associated with pathologic evidence of inflammation [93% versus 7%]. The quality of inflammation in the stented groups also differed. Ninety percent of the stented arteries in groups 1 and 2 had acute inflammation, compared to only 20% in group 3. The remainder of the stented arteries in group 3 had chronic inflammation or were normal. CONCLUSION: In the swine model, intravascular metallic stents have the potential to become infected. This is associated with acute inflammation of the arterial wall and vessel thrombosis. Further studies evaluating the incidence of stent infections in humans are needed.

Lessons learned from the DIASTAT vascular access graft.

BACKGROUND: The vascular community continues to search for the ideal vascular access graft that will allow early cannulation and avoid temporary central venous catheters. METHODS: This is a review of the Cranley Surgical Associates' experience with the use of the Gore-Tex DIASTAT (W.L. Gore & Associates, Inc., Flagstaff, Arizona) vascular access graft in 20 patients compared with 20 control patients matched for age, sex and risk factors. RESULTS: Although the DIASTAT graft is touted for early accessibility and decreased need for central venous access, that was not found to be the case as 14 patients in the DIASTAT group received temporary access catheters. There was significantly more edema in the DIASTAT patients (P = 0.0048). Comparing the time to the first thrombosis or to revision revealed an average of 18 weeks for the DIASTAT group and 56 weeks for the control group. The length of time to thrombosis or revision was significantly longer in the control group (P = 0.0058). Comparison of the number of weeks of function and serviceability of the grafts revealed the average DIASTAT graft functioned for 34 weeks and that of the control group for an average of 70 weeks (P = 0.0131). Comparison of the two groups showed a significant increase in early thrombotic events (< 90 days) in the DIASTAT grafts (P = 0.0013). CONCLUSIONS: The DIASTAT vascular access graft does not appear to be the ideal hemodialysis access graft.

Endovascular stent infection with delayed bacterial challenge.

BACKGROUND: Reports of endovascular stent infection have recently been described. The purpose of this study was to determine if intravascular metallic stents in a swine model could become infected following a bacterial challenge given remote from the time of stent placement. METHODS: Balloon expandable metallic stents (Palmaz) were implanted in the iliac arteries of 14 swine. An angioplasty, without stent placement, was also performed in the contralateral iliac artery. An intravenous bacterial challenge with Staphylococcus aureus was given 4 weeks after stent placement. Euthanasia was performed 72 hours after the bacterial challenge. At the time of euthanasia, the iliac artery/stent complex and the contralateral angioplastied iliac artery were harvested and sent for microbiologic and pathologic analysis. RESULTS: Seven of the 14 stent/artery complexes were culture positive for S aureus whereas only one of the 14 angioplastied arteries was positive for S aureus (P = 0.03). On histologic examination, 6 of the 14 stent/artery complexes had evidence of acute inflammatory changes in the arterial wall. This compares with only 1 of 14 angioplastied arteries having evidence of inflammatory infiltrate in the arterial wall (P = 0.07). All 6 of the stent/artery complexes with inflammatory infiltrate were culture positive. CONCLUSION: In the swine model, intravascular metallic stents have the potential to become infected when a bacterial challenge is given 4 weeks after stent placement. Further studies evaluating the incidence of stent infections in humans are needed.

Infectibility of endovascular stents following antibiotic prophylaxis or after arterial wall incorporation.

BACKGROUND: Case reports of endovascular stent infection have been accumulating in the last several years. We sought to determine if prophylactic antibiotics would prevent stent/artery complex infections in a swine model if given before a bacterial challenge at the time of stent placement and 4 weeks following deployment. We also investigated whether arterial wall incorporation protected the stent against infection without antibiotic prophylaxis. METHODS: Balloon expandable Palmaz stents were placed in the iliac arteries of 42 swine. At the same time, angioplasty was performed on the contralateral iliac artery as a control. In group A, prophylactic cefazolin was given to 12 swine at the time of stent deployment followed by an intraaortic bacterial challenge of Staphylococcus aureus. In group B, 10 swine received prophylactic cefazolin followed by intravenous S aureus 4 weeks after iliac stenting and angioplasty. In group C, 3 months following iliac stent placement and angioplasty an intravenous bacterial challenge was administered with S aureus. All swine were euthanized, and the iliac stent/artery complex and the contralateral angioplastied iliac artery were harvested and sent for culture and pathology. Experimental groups were compared with results from our previously published swine infection model using the Fisher's exact test. P values were considered significant if less than 0.05. RESULTS: Group A: Two of the 12 (17%) stent/artery complexes in the antibiotic treatment group had positive cultures. This compares with 7 of 10 (70%) in the control group (P = 0.016). In addition, there was one infection in an angioplastied vessel contralateral to one of the two stent infections. Molecular strain typing verified that the positive cultures were the same strain that was used to challenge the animals. No vessel thrombosis occurred in the stented arteries even in the presence of infection. Group B: One of 10 (10%) stented iliac arteries had a culture positive infection. This compares with 7 of 14 (50%) positive cultures in the control group (P = 0.04). In addition, one angioplastied vessel did have mild S aureus growth on culture. Both positive cultures were verified to be the same as the injected strain by molecular strain typing. There were no thrombosed or occluded vessels. Group C: One of 15 patent stents had growth of S aureus on culture and evidence of acute inflammation on histopathologic examination. The stent infection rate of 1 of 15 (7%) patent stents in this study was significantly less than the infection rates with bacterial challenge at placement (7 of 10, 70%; P < 0.01) and at 1 month postplacement (7 of 14, 50%; P = 0.0142). Five stents occluded without evidence of infectious cause. CONCLUSIONS: The results of this study support a recommendation that antibiotic prophylaxis should be used at the time of arterial stent placement and early after placement at times of anticipated bacteremia, but indefinite prophylaxis may be unnecessary due to arterial wall incorporation of the stent.