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David P Foley

Publications and source records attributed to David P Foley.

At least 19 recordsLinked to original sources
PubMed2006

Interleukin-6 and STAT3 protect the liver from hepatic ischemia and reperfusion injury during ischemic preconditioning.

BACKGROUND: Ischemic preconditioning has been shown to protect the liver from ischemia/reperfusion injury. We hypothesized that IL-6 directly modulates the protective effects of ischemic preconditioning. METHODS: Three weeks after undergoing splenic transposition, wild-type C57BL/6 and IL-6 null mice underwent 75 minutes of total hepatic ischemia with or without prior ischemic preconditioning (10 minutes of ischemia followed by 15 minutes of reperfusion). After reperfusion, serum ALT, serum IL-6, hepatic IL-6 mRNA, hepatic pSTAT3, and liver histology were evaluated. RESULTS: In wild-type mice, survival at 24 hours was greater in the preconditioned group compared with the non-preconditioned group (75% vs 40%, P<.05). In IL-6 null mice, however, ischemic preconditioning did not improve survival when compared with the non-preconditioned group. Preconditioning significantly reduced hepatocellular injury in wild-type mice (P<.05) when compared with IL-6 null animals. This protection was associated with significant increases in serum IL-6, hepatic IL-6 mRNA, and hepatic pSTAT3 levels (P<.05). The protective effects of ischemic preconditioning that correlated with significant increases in systemic IL-6, hepatic IL-6 mRNA abundance, and pSTAT3 levels, were not observed in IL-6 null mice. CONCLUSIONS: The protective effects of ischemic preconditioning during total hepatic ischemia/reperfusion injury are dependent on IL-6 signaling and are associated with increased phosphorylation of hepatic STAT3.

Alanine Transaminase↗
PubMed2006

Portal vein resection for hilar cholangiocarcinoma.

Hilar cholangiocarcinoma remains a difficult challenge for the surgeon. Achieving negative surgical margins when resecting this relatively uncommon tumor is technically demanding as a result of the close proximity of the bile duct bifurcation to the vascular inflow of the liver. A recent advance in surgical treatment is the addition of portal vein resection to the procedure. Resection of the portal vein increases the number of patients offered a potentially curative approach but is technically more difficult and may increase the risk of the procedure. This study reviews the results of portal vein resection for hilar cholangiocarcinoma. Between 1998 and 2005, 60 patients underwent potentially curative resections of hilar cholangiocarcinoma. Mean patient age was 64 +/- 12 years (range, 24-85 years). Liver resections performed along with biliary resection included 49 trisegmentectomies (37 right, 12 left) and 10 lobectomies (8 left, 2 right). One patient had only the bile duct resected. Four patients also had simultaneous pancreaticoduodenectomy performed. Twenty-six patients required portal vein resection and reconstruction to achieve negative margins, 3 of which also required reconstruction of the hepatic artery. Operative mortality was 8 per cent with an overall complication rate of 40 per cent. Patients who underwent portal vein resection had an operative mortality of 4 per cent, which was not different from the 12 per cent mortality in patients who did not undergo portal vein resection (P = 0.39). There was no difference in actuarial patient survival between patients who underwent portal vein resection and those who did not (5-year survival 39 per cent vs. 41 per cent, P = not significant). Negative margins were achieved in 80 per cent of cases and were associated with improved survival (P < 0.01). Five-year actuarial survival in patients undergoing resection with negative margins was 45 per cent. There was no difference in margin status or long-term survival between those patients who underwent portal vein resection and those who did not. Only negative margin status was associated with improved survival by multivariate analysis. Portal vein resection for hilar cholangiocarcinoma is safe and allows a chance for long-term survival in otherwise unresectable patients.

Adult↗
PubMed2005

Aortic hypoplasia and right ventricular outflow tract obstruction in a young man with uncontrolled hypertension.

We report the case of a 35-year-old man who presented to hospital with symptomatic uncontrolled hypertension. He had no other conventional cardiovascular risk factors, but did have previous cataract surgery and patent ductus arteriosus repair. Echocardiography revealed normal valves, right ventricular outflow tract obstruction, and heavy calcification of the aortic root compromising luminal diameter. Pulmonary angiography confirmed supravalvular and subvalvular pulmonary stenosis. Aortography showed hypoplasia of the entire aortic trunk extending into the iliac arteries, but without involvement of other major branches. A possible unifying diagnosis, with the combination of aortic hypoplasia, pulmonary artery stenosis, patent ductus arteriosus, and cataracts, was believed to have been congenital rubella syndrome. Although associated with numerous cardiovascular abnormalities, aortic hypoplasia is an extremely rare manifestation of congenital rubella that, to our knowledge, has been reported in only two cases in the literature to date.

Adult↗
PubMed2005

Splenic transposition is superior to caudal shunt as a model of murine total hepatic ischemia.

Murine total hepatic ischemia (THI) followed by reperfusion without shunting of the portal vein induces significant lethality in rodents due to intestinal congestion. Two methods have been promulgated to study THI and reperfusion in mice without intestinal congestion: subcutaneous splenic transposition which creates a portosystemic shunt via epigastric vessels, and a caudal shunt with 30% hepatectomy, which creates a portosystemic shunt via the small remnant of remaining caudal lobe. We compared outcome, inflammatory response and hepatic injury due to THI and reperfusion in these two models. Female C57BL/6 mice underwent ST, caudal shunt or no surgery prior to having 30 min of total hepatic ischemia followed by 60 min of reperfusion. Survival, surgical complications, serum AST/ALT and IL-6 were determined. Apoptotic and necrotic hepatocytes were identified by morphological criteria. Complication rates for the ST and caudal shunt procedures were 6.7 and 20%, respectively. Subsequent mortality rates following THI and 60 min reperfusion were 5.9 and 50% in mice with ST and caudal shunt, respectively. Both groups had elevated serum AST/ALT concentrations. However, in mice undergoing caudal shunt, AST/ALT levels were also significantly increased even without THI. The number of apoptotic hepatocytes after THI and reperfusion in mice following caudal shunt was significantly higher compared with those of ST (P<0.001). Both ST and caudal shunt can be used in models of THI and reperfusion to prevent significant lethality due to intestinal congestion. However, ST is a simple, safe and suitable model, whereas caudal shunt requires manipulation of the liver, and is associated with significant hepatic injury and morbidity.

Animals↗
PubMed2005

Surgical management of hilar cholangiocarcinoma.

OBJECTIVE: To assess the surgical management of hilar cholangiocarcinoma over a time period when liver resection was considered standard management. SUMMARY BACKGROUND DATA: Hilar cholangiocarcinoma remains a difficult challenge for surgeons. An advance in surgical treatment is the addition of liver resection to the procedure. However, liver resection in the setting of liver dysfunction caused by biliary obstruction can be associated with increased mortality. METHODS: Between 1997 and 2004, 80 patients with hilar cholangiocarcinoma having surgery were reviewed. Fifty-three patients had attempted curative resections, 14 patients had palliative bypasses, while 13 patients had findings that precluded any further intervention. Twenty-three patients required portal vein resection and reconstruction to achieve negative margins, 3 of which also required reconstruction of the hepatic artery. RESULTS: Patients undergoing resection had a 9% operative mortality, with morbidity of 40%. Patients who demonstrated lobar hypertrophy preoperatively due to tumor involvement of the contralateral liver or induced with portal vein embolization (PVE) had a significantly lower operative mortality than those patients without hypertrophy. Median overall survival in patients resected was 40 months, with 5-year survival of 35%. Negative margins were achieved in 80% of cases and were associated with improved survival. Five-year survival in patients undergoing resection with negative margins was 45%. CONCLUSION: Combined liver and bile-duct resection can be performed for hilar cholangiocarcinoma with acceptable mortality, though higher than that for liver resections performed for other indications. The use of PVE in cases where hypertrophy of the remnant liver has not occurred preoperatively may reduce the risk of operative mortality.

Adult↗
PubMed2005

Simultaneous pancreas-kidney transplantation from donation after cardiac death: successful long-term outcomes.

OBJECTIVE: The outcomes of simultaneous pancreas-kidney (SPK) transplantation with donor organs procured from donation after cardiac death (DCD) are compared with transplants performed with donor organs recovered from donation after brain death (DBD). SUMMARY BACKGROUND DATA: Concerns exist regarding the utilization of pancreata obtained from DCD donors. While it is known that DCD kidneys will have a higher rate of DGF, long-term functional graft survival data for DCD pancreata have not been reported. METHODS: A retrospective review of all DCD SPK transplants performed at a single center was undertaken. RESULTS: Patient, pancreas, and kidney survival at 5 years were similar between DCD and DBD organs. Pancreas function and outcomes were indistinguishable between the 2 modes of procurement. As expected, the DCD kidneys had an elevated rate of DGF, which had no significant long-term clinical impact. CONCLUSION: SPK transplantation using selected DCD donors is a safe and viable method to expand the organ pool for transplantation.

Adult↗
PubMed2005

Donation after cardiac death: the University of Wisconsin experience with liver transplantation.

OBJECTIVE: To determine whether the outcomes of liver transplantation (LTx) from donation after cardiac death (DCD) donors are equivalent to those from donation after brain death (DBD) donors. SUMMARY BACKGROUND DATA: Because of the significant donor organ shortage, more transplant centers are using livers recovered from DCD donors. However, long-term, single-center outcomes of liver transplantation from DCD donors are limited. METHODS: From January 1, 1993, to July 31, 2002, 553 liver transplants were performed from DBD donors and 36 were performed from DCD donors. Differences in event rates between the groups were compared with Kaplan-Meier estimates and the log-rank test. Differences in proportion and differences of means between the groups were compared with Fisher exact test and the Wilcoxon rank sum test, respectively. RESULTS: Mean warm ischemic time at recovery in the DCD group was 17.8 +/- 10.6 minutes. The overall rate of biliary strictures was greater in the DCD group at 1 year (33% versus 10%) and 3 years (37% versus 12%; P = 0.0001). The incidence of hepatic artery thrombosis, portal vein stenosis/thrombosis, ischemic-type biliary stricture (ITBS), and primary nonfunction were similar between groups. However, the incidence of both hepatic artery stenosis (16.6% versus 5.4%; P = 0.001) and hepatic abscess and biloma formation (16.7% versus 8.3%; P = 0.04) were greater in the DCD group. Trends toward worse patient and graft survival and increased incidence of ITBS were seen in DCD donors greater than 40 years compared with DCD donors less than 40 years. Overall patient survival at 1 year (DCD, 80%; versus DBD, 91%) and 3 years (DCD, 68%; versus DBD, 84%) was significantly less in the DCD group (P = 0.002). Similarly, graft survival at 1 year (DCD, 67%; versus DBD, 86%) and 3 years (DCD, 56%; versus DBD, 80%) were significantly less in the DCD group (P = 0.0001). CONCLUSIONS: Despite similar rates of primary nonfunction, LTx after controlled DCD resulted in worse patient and graft survival compared with LTx after DBD and increased incidence of biliary complications and hepatic artery stenosis. However, overall results of LTx after controlled DCD are encouraging; and with careful donor and recipient selection, LTx after DCD may successfully increase the donor liver pool.

Adult↗
PubMed2005

Are we frozen in time? Analysis of the utilization and efficacy of pulsatile perfusion in renal transplantation.

Preservation techniques are crucial to deceased donor kidney transplantation (DDTx), but the efficacy of pulsatile perfusion (PP) versus cold storage (CS) remains uncertain. We describe patterns of PP use and explore four fundamental questions. What kidneys are selected for PP? How does PP affect utilization of donated kidneys? What effect does PP have on outcomes? When does PP appear to be most efficacious? We examined rates of PP in DDTx in the United States from 1994 to 2003. We generated models for organ utilization, delayed graft function (DGF) and for the use of PP. We analyzed the long-term effect of PP with multivariate Cox models. The utilization rates for non-expanded criteria donors (ECDs) were similar by storage type, but for ECDs there was a significantly higher utilization rate with PP (70% with PP vs. 59% with CS, p < 0.001). Use of PP was widely variable across transplant centers. DGF rates were significantly lower with PP (27.6% vs. 19.6%). PP was associated with a mild benefit on death censored graft survival (adjusted hazard ratio = 0.88, 95% CI 0.85-0.91). Reduced DGF and significantly lower discard rates of ECDs associated with PP suggest an important utility of PP in renal transplantation. Additional evidence of improvement in graft survival, particularly in more recent years, provides further encouraging evidence for the use of PP.

Cadaver↗
PubMed2004

Superior long-term results of simultaneous pancreas-kidney transplantation from pediatric donors.

The shortage of cadaveric donors for simultaneous pancreas-kidney transplantation has prompted the use of cadaveric organs from pediatric donors. The long-term outcome and its impact on overall long-term survival are unknown. A total of 680 recipients receiving cadaver Simultaneous pancreas-kidney (SPK) transplantation from pediatric and adult donors between July 1986 and September 2001 were analyzed and compared. Ten-year kidney and pancreas graft survival for SPK transplantation from donors aged <18 years (n = 142) were 80% and 72%, respectively, compared to 61% pancreas and kidney graft survival from donors > or =18 years of age (n = 538; p = 0.03 and 0.05, respectively). Five years post-transplant, blood glucose, HbA1c and creatinine clearance were significantly better in recipients from pediatric donors (85.3 +/- 13 mg/dL, 5.5 +/- 3.5% and 65.6 +/- 16 mL/min, respectively), compared to recipients from adult donors (95.1 +/- 29 mg/dL, 5.9 +/- 3.5% and 58.3 +/- 17 mL/min; p = 0.001, 0.01 and 0.002, respectively). Causes of graft failure for kidney and pancreas transplants were similar between the two groups. No statistically significant difference was observed in patient survival between recipients from pediatric donors compared to adult donors (85% vs. 76%, p = 0.29). When recipients of SPK from pediatric donors were stratified according to age (3-11 years and 12-17 years) and compared, no difference in kidney or pancreas graft survival was observed (kidney 76.4% vs. 81.3%, p = 0.15; pancreas 75% vs. 76%, p = 0.10, respectively). Pediatric donors represent a valuable source of organs, providing excellent short- and long-term outcomes. Wide utilization of pediatric organs will substantially increase the donor pool.

Adolescent↗
PubMed2004

Donation after cardiac death: the university of wisconsin experience with renal transplantation.

Owing to the shortage of organ donors, there is renewed interest in donation after cardiac death (DCD), formerly referred to as nonheart-beating donation. From January 1984 until August 2000, 382 renal transplants were performed from DCD donors. These were compared with 1089 renal transplants performed from donation after brain death (DBD) donors. The mean warm ischemic time in DCD donors was 16.5 min. There was no statistical difference in cold ischemic time, rate of primary nonfunction, or graft loss in the first 30 days after transplantation. The rate of delayed graft function (DGF) was higher for DCD donors (27.5% vs. 21.3%; p = 0.016) and discharge creatinine was higher in DCD donors (1.92 mg/dL vs. 1.71 mg/dL; p = 0.001). There was no statistical difference in the 5-, 10-, or 15-year allograft survival when DCD donors were compared with DBD donors (64.8%, 44.8%, 27.8% vs. 71.3%, 48.3%, 33.8%; p = 0.054). Likewise, no statistical difference in the rate of technical complications was seen. Our long-term data indicate that the results of renal transplantation from DCD donors are equivalent to long-term allograft survival from DBD donors despite an increase in the rate of DGF. Organ procurement organizations, transplant centers, and hospitals should work to expand the implementation of DCD policies.

Adult↗
PubMed2004

Effect of sirolimus withdrawal in patients with deteriorating renal function.

Sirolimus has been an important addition to immunosuppressive regimens utilized in kidney transplantation. However, sirolimus can potentiate calcineurin inhibitor (CNI) nephrotoxicity by some still uncertain mechanisms. Studies have demonstrated that withdrawal of a CNI under sirolimus immunosuppression can improve renal function. However, it has yet to be demonstrated that withdrawal of sirolimus from such a regimen can also improve renal function and reverse progressive functional deterioration. We studied 17 patients who developed deterioration of renal function while on a CNI and sirolimus. Once an established deterioration in renal function was noted, sirolimus was withdrawn from the regimen and replaced with mycophenolate mofetil. Out of 17 patients with a negative slope in 1/cr, 15 demonstrated a positive treatment effect (change to a positive slope). On aggregate, renal function improved by 18% (creatinine 2.75-2.24 mg/dL), LDL cholesterol improved, as did hematocrit values after withdrawal. The majority of patients on a CNI and sirolimus regimen who experience deterioration in renal function demonstrate improvement in renal function after withdrawal of sirolimus. This strategy may be particularly useful in those patients where CNI withdrawal is considered to be of high immunologic or metabolic risk.

Adult↗
PubMed2004

Clinical and angiographic safety and efficacy trial with a new coronary stent: the RESTOR study of the R Stent.

The RESTOR trial (R Stent Efficacy and Safety Trial by ORBUS) is an efficacy and safety evaluation of the R Stent for treatment of patients with a single de novo coronary lesion < 25 mm in length in a coronary artery of 2.75-4.0 mm diameter. This new stent utilizes a patented dual helix design for radial strength and flexibility. The aim of the study was to assess major adverse cardiac events (MACE) and angiographic outcome at 6 months after implantation. From May to December 2000 a total of 121 patients with symptomatic stable or unstable angina pectoris or documented silent ischemia and a significant single, de novo coronary lesion (average reference vessel diameter 2.84 +/- 0.54 mm, average lesion length 10.53 +/- 3.70 mm) were included in two Dutch centers. All patients were treated with clopidogrel 75 mg/day for 1 month and with aspirin greater than or equal to 100 mg/day. The angiographic success rate (< 30% diameter stenosis post-procedure) was 98.3%. Procedural success (angiographic success without in-hospital MACE) was 95.9%. The 6-month MACE rate was 12.4%. 101 of the 121 patients had an angiographic follow-up at 6 months. Minimal lumen diameter pre-/post-procedure and at follow-up was 0.98 +/- 0.37, 2.64 +/- 0.38 and 1.85 +/- 0.68 mm, respectively. The resulting binary restenosis rate in this population was 20.8%. The coronary R Stent is safe and effective as a primary device for the treatment of native coronary lesions in patients with stable or unstable angina pectoris, and well suitable as a platform for a drug eluting stent.

Adult↗
PubMed2003

Sirolimus-eluting stent for treatment of complex in-stent restenosis: the first clinical experience.

OBJECTIVES: In this study, we assess the value of sirolimus eluting stent (SES) implantation in patients with complex in-stent restenosis (ISR). BACKGROUND: The treatment of ISR remains a therapeutic challenge, since many pharmacological and mechanical approaches have shown disappointing results. The SESs have been reported to be effective in de-novo coronary lesions. METHODS: Sixteen patients with severe, recurrent ISR in a native coronary artery (average lesion length 18.4 mm) and objective evidence of ischemia were included. They received one or more 18 mm Bx VELOCITY SESs (Cordis Waterloo, Belgium). Quantitative angiographic and three-dimensional intravascular ultrasound (IVUS) follow-up was performed at four months, and clinical follow-up at nine months. RESULTS: The SES implantation (n = 26) was successful in all 16 patients. Four patients had recurrent restenosis following brachytherapy, and three patients had totally occluded vessels preprocedure. At four months follow-up, one patient had died and three patients had angiographic evidence of restenosis (one in-stent and two in-lesion). In-stent late lumen loss averaged 0.21 mm and the volume obstruction of the stent by IVUS was 1.1%. At nine months clinical follow-up, three patients had experienced four major adverse cardiac events (two deaths and one acute myocardial infarction necessitating repeat target vessel angioplasty). CONCLUSIONS: The SES implantation in patients with severe ISR lesions effectively prevents neointima formation and recurrent restenosis at four months angiographic follow-up.

Adult↗