T. Jakimowicz

Bioengineered human acellular vessels for dialysis access in patients with end-stage renal disease: two phase 2 single-arm trials

BACKGROUND For patients with end-stage renal disease who are not candidates for fistula, dialysis access grafts are the best option for chronic haemodialysis. However, polytetrafluoroethylene arteriovenous grafts are prone to thrombosis, infection, and intimal hyperplasia at the venous anastomosis. We developed and tested a bioengineered human acellular vessel as a potential solution to these limitations in dialysis access. METHODS We did two single-arm phase 2 trials at six centres in the USA and Poland. We enrolled adults with end-stage renal disease. A novel bioengineered human acellular vessel was implanted into the arms of patients for haemodialysis access. Primary endpoints were safety (freedom from immune response or infection, aneurysm, or mechanical failure, and incidence of adverse events), and efficacy as assessed by primary, primary assisted, and secondary patencies at 6 months. All patients were followed up for at least 1 year, or had a censoring event. These trials are registered with ClinicalTrials.gov, NCT01744418 and NCT01840956. FINDINGS Human acellular vessels were implanted into 60 patients. Mean follow-up was 16 months (SD 7·6). One vessel became infected during 82 patient-years of follow-up. The vessels had no dilatation and rarely had post-cannulation bleeding. At 6 months, 63% (95% CI 47-72) of patients had primary patency, 73% (57-81) had primary assisted patency, and 97% (85-98) had secondary patency, with most loss of primary patency because of thrombosis. At 12 months, 28% (17-40) had primary patency, 38% (26-51) had primary assisted patency, and 89% (74-93) had secondary patency. INTERPRETATION Bioengineered human acellular vessels seem to provide safe and functional haemodialysis access, and warrant further study in randomised controlled trials. FUNDING Humacyte and US National Institutes of Health.

Vascular Access for Haemodialysis in Patients with Central Vein Thrombosis

OBJECTIVES Dialysis-dependent patients often have central venous drainage complications. In patients with functioning arm arteriovenous fistula, this may result in venous hypertension, arm oedema and vascular access failure. Percutaneous angioplasty and stent implantation might be inadequate to resolve these issues. In these cases, new access can potentially be created with anastomosis to the subclavian vein, iliac vein or vena cava or by making a veno-venous graft to bypass the thrombosis. The aim of this study was to assess the utility of unusual bypasses in vascular access in patients with the central vein thrombosis. MATERIALS A total of 49 patients were treated. The mean number of previous vascular access surgery procedures was 7.6 (3-17). We performed 19 axillo-iliac, 14 axillo-axillary bypasses and 16 conduits from the arm fistula to the jugular (nine conduits) or subclavian (seven conduits) vein for haemodialysis purposes. RESULTS All fistulas except one were used for haemodialysis. One patient died before the first use of the fistula. At 12 months, the primary, primary assisted and secondary patency rates were 85.4%, 89.6% and 95.8%, respectively. The follow-up period ranged from 1 to 84 months. CONCLUSION Unusual grafts are an efficient option as a permanent vascular access for haemodialysis purposes in patients with central vein occlusion.

Is Severe Atherosclerosis in the Aortoiliac Region a Contraindication for Kidney Transplantation

BACKGROUND Atherosclerosis is common in end-stage renal disease patients on dialysis. However, it has previously been considered to be a relative contraindication to kidney transplantation. Currently, patients with extended indications are accepted onto the waiting list, including those with severe atherosclerosis. These patients require vascular procedures before or during kidney transplantation. The aim of this study was to present our experience with vascular reconstruction before kidney transplantation. MATERIAL AND METHODS Twelve atherosclerotic, uremic patients referred to be candidates for kidney transplantation were refused because of occlusive lesions of the iliac arteries or the distal aorta. The 10 males and 2 females had an age range of 45 to 68 years. Preoperative assessments consisted of a Doppler ultrasound and an angio computed tomography scan. The reconstructions were performed with aorto-biliac, aorto-bifemoral, or ilio-femoral dacron grafts in 7, 4, and 1 patient, respectively, under general anesthesia. RESULTS There were no major postoperative complications; the patients were discharged and placed on a special waiting list. Eight patients received kidney allografts, including one living-related transplantation. All procedures were performed with arterial anastomosis of the transplanted kidney to the side of the prosthesis. No patient developed signs of arterial graft infection. In the postoperative period, there were no arterial or transplanted kidney-related complications, except for delayed graft function in four cases. The remaining four patients are still on the waiting list. CONCLUSION In end-stage renal disease patients with severe atherosclerosis in the aortoiliac region, vascular reconstruction allows kidney transplantation.

Surgical Complications Related to Transplanted Pancreas After Simultaneous Pancreas and Kidney Transplantation

OBJECTIVE Simultaneous pancreas and kidney transplantation (SPTKx) is characterized by the high rate and variability of postoperative complications, which could be a limitation of this treatment. The aim of this study was to evaluate prevalence, types, and severity of postoperative complications due to pancreas graft among the simultaneous pancreas and kidney recipients. METHODS Postoperative complications related to transplanted pancreas among 112 SPTKx recipients were analyzed. The cumulative survival rates for pancreas graft function and cumulative freedom from complication on day 60 after transplantation were assessed. Severity of complications was classified according to a modified Clavien-Dindo scale. RESULTS The 12-month cumulative survival rate for pancreatic graft was 0.74. Cumulative freedom from complication on the 60th day after transplantation was 0.57. The rates for II, IIIA, IIIB, IVA, and IVB severity grades were 10,6%, 4,5%, 19,7%, 44%, and 21,2%, respectively. The most severe (IVB) transplanted pancreas complications were due to graft inflammation, infection, pancreatic abscess, and local or diffuse necrosis. The most frequent reason for graft pancreatectomy was vascular thrombosis 35.9% (14/39). The mortality rate after graft pancreatectomy was significantly lower for vascular thrombosis than for infection (0/14 vs 11/25; P < .05). CONCLUSION Reducing vascular thrombosis could preserve graft function rate. Preventing graft inflammation and infection would reduce mortality.

Influence of Simultaneous Pancreas and Preemptive Kidney Transplantation on Severity of Postoperative Complications

BACKGROUND Simultaneous pancreas and preemptive kidney transplantation (SPpreKT) seems to be the optimal treatment for the patients with diabetes type 1 who are progressing to end-stage renal disease. On the other hand, surgical complications with a high rate of relaparatomy are a limiting factor in pancreas transplantation. OBJECTIVE Comparison of severity of surgical complications was performed between a group of preemptive (SPpreKT group) and nonpreemptive recipients of SPKT (SPKT group). METHODS Between 1988 and 2010, we performed 112 SPKTs including 25 preemptive recipients (22.3%). The SPKT Group included 87 recipients (77.7%). The severity of complications was classified according to a modified Clavien scale: grade I, no complication; grade II, drug therapy; grade IIIA, invasive intervention not requiring general anesthesia; grade IIIB, invasive intervention requiring general anesthesia; grade IVA, graft failure; and grade IVB, death. RESULTS Among the SPpreKT group, 64% of recipients were free from postoperative complications compared with 40.3% of the SPKT group (P<.01). Among the SPKT group, 52 recipients (59.7%) developed 58 postoperative complications, including 15 (17.3%) deaths due to graft pancreatitis (80%) or pancreatic fistula (20%). Among the SPpreKT group, 9 recipients developed 9 complications. None of the preemptively transplanted group subjects experienced a lethal complication. Among the SPpreKT group, the most severe complication was graft pancreatitis leading to graft removal in 2 recipients. CONCLUSIONS Recipients of preemptive SPKT developed significantly fewer postoperative complications, especially deaths. However the rates of mild (II, IIIA) and moderate (IIIB) complications as well as graft failures (IVA) were similar to the nonpreemptive group.

Usefulness of 16-Row Multidetector Computed Tomography With Volume Rendering and Maximum Intensity Projection Reconstruction as a Monitor Pancreatic Graft Vessel Patency During the Early Postoperative Period

Thrombosis of the pancreatic graft vessels is the most common complication after transplantation. It leads to loss of 5% to 8% of grafts during the early postoperative period. The aims of this study were to evaluate the usefulness of 16-row multidetector computed tomography (16-MDCT) with volume rendering (VR) and maximum intensity projection (MIP) reconstruction to monitor pancreatic graft vessel patency during the early postoperative period and the efficacy of a heparin infusion as a treatment for graft thrombosis. Among 40 consecutive simultaneous pancreas-kidney transplant recipients, 16-MDCT was performed at 6 to 8 days after the operation. Secondary reconstructions were obtained with VR and MIP algorithms to evaluate the morphology and patency of the extra- and intrapancreatic arteries and veins. In cases of thrombosis, every patient was treated with an infusion of unfractionated heparin. In 15 recipients, thrombosis of the large vessels was detected by 16-MDCT. Heparin infusions saved five pancreatic grafts (5/15; 33.3%), but the other 10 pancreatic grafts were removed. In another four recipients (4/40; 10%) the thrombi were localized only in small intrapancreatic vessels. Treatment with heparin infusion was successful in 3/4 (75%) cases with patent vessels upon control computed tomography examination. We compared the efficacy of heparin treatment depending on the diameter of the thrombosed vessel, observing a significant difference (5/15 vs 3/4; P < .01; chi-square). 16-MDCT with secondary reconstruction by application of VR and MIP algorithms was an efficient method to visualize not only large pancreatic graft arteries and veins but also intrapancreatic parenchymal vessels. In cases of thrombosis of small intrapancreatic vessels, unfractionated heparin infusion significantly decreased graft loss.

Do high levels of serum triglycerides in pancreas graft recipients before transplantation promote graft pancreatitis

OBJECTIVE Graft pancreatitis is a serious complication following pancreas transplantation. The aim of this study was to evaluate the influence of pretransplant serum lipid levels on the development of graft pancreatitis among patients undergoing simultaneous pancreas and kidney transplantation (spkTx). METHODS We reviewed data from spkTx patients engrafted between 1999 and 2002. Group 1 consisted of 10 recipients with well-established pancreas and kidney graft function without postoperative pancreatitis; group 2 5 spkTx recipients who developed fatal graft pancreatitis in the first posttransplant month. The lipid parameters evaluated within 1 hour before transplantation and after hemodialysis included total cholesterol, HDL, LDL, VLDL, triglicerides and apoproteins A and B. RESULTS Triglycerides, apoprotein B and VLDL were significantly increased just before transplantation among patients who developed fatal pancreatitis compared to those patients with good graft function. CONCLUSION Recipient hypertriglyceridemia promotes graft pancreatitis in previously injured pancreatic graft.

Early Complications Related to the Transplanted Kidney After Simultaneous Pancreas and Kidney Transplantation

OBJECTIVE Simultaneous pancreas and kidney transplantation (SPKTx) is the most often performed multiorgan transplantation. The main source of complication is transplanted pancreas; as a result, early complications related to kidney transplant are rarely assessed. The aim of this study was to evaluate prevalence, types, and severity of postoperative complications due to kidney graft among the simultaneous pancreas and kidney recipients. METHODS Complications related to transplanted kidney among 112 SPKTx recipients were analyzed. The indication for SPKTx was end-stage diabetic nephropathy due to long-lasting diabetes type 1. The cumulative survival rates for kidney graft function and cumulative freedom from complication on days 60 and 90 after transplantation were assessed. Severity of complications was classified according to the modified Dindo-Clavien scale. RESULTS The 12-month cumulative survival rate for kidney graft was 0.91. Cumulative freedom from complication on the 60th day after transplantation was 0.84. The rates for II, IIIA, IIIB, IVA, and IVB severity grades were: 34.9%, 4.3%, 26.1%, 26.1%, and 8.6%, respectively. Acute tubular necrosis and rejection were the most frequent (43.4%) cause of complication. The most frequent reasons for graft nephrectomy were infections (2/7; 28.6%) and vascular thrombosis due to atherosclerosis of recipient iliac arteries (2/7; 28.6%). The most severe (IVB) complications were caused by fungal infection. CONCLUSION Rate and severity of complications due to renal graft after SPKTx was low; however, to prevent the most serious ones reduction of fungal infection was necessary.

Influence of Atheromatous Lesions in the Ilio-Femoral Segment on the Occurrence of Stentgraft Thrombosis After Endovascular Treatment of an Abdominal Aortic Aneurysm

UNLABELLED Limb graft thrombosis (LGT) is one of the most frequent severe complications after endovascular repair of abdominal aortic aneurysms. The aim of the study was to assess the influence of atherosclerosis in ileo-femoral segment on the incidence of LGT as well as to analyze the methods of treatment of LGT. MATERIAL AND METHODS The medical records of 564 consecutive patients operated endovascularly for abdominal aortic aneurysm by means of bifurcated stentgrafts in the Department of General, Vascular and Transplantat Surgery of Medical University of Warsaw were analyzed. The minimal observation time after surgery was one year. Patients with inflammatory, ruptured and falls aneurysms as well as those with the observation period below 12 months were excluded from the study. Patients were divided into two groups: test (B) and control (K) depending on the progression of atherosclerosis in the iliac arteries. Group B included 184 patients (13 women and 171 men), with advanced atherosclerotic lesions of ilio-femoral segment, corresponding to the A - C class in the TASC classification. The remaining 380 patients (25 women and 355 men) without significant blood flow disorders in the iliac arteries, constituted the group K. The computed tomography was done in all patients with acute limb ischemia. RESULTS During the observation time up to 114 month, the LGT occurred in 43 (7.6%) cases: [group B - 34/184 (18.5%), group K - 9/380 (2.4%)]. The treatment of LGT included an attempt of patency restoring of the prosthesis by means of thrombolysis or thrombectomy combined with stenting. In case of failure the cross-over femoro-femoral bypass was implanted. Thrombectomy was successful in 21 of 40 cases (52.5%), the local thrombolysis was done in 5 patients and it was successful in three cases and in the remaining two patients the thrombectomy was done. In 16 of 24 patients after patency restoring of the prosthesis the angioplastics and stenting was done. In 17 cases the femoro-femoral bypass was implanted. CONCLUSIONS The atherosclerosis in ileo-femoral segment significantly increases the risk of LGT. An attempt of patency restoring (thrombectomia or thrombolysis) combined with stenting and cross-over femoro- femoral bypass implantation in case of failure seems to be the successful method of LGT treatment.

Influence of the Primary Disease on Rehabilitation Results in the Early Postoperative Period in Patients After Orthotopic Liver Transplantation

BACKGROUND Rehabilitation after orthotropic liver transplantation (OLT) is a difficult clinical problem due to severe comorbidities and complications. We evaluated the rehabilitation progress in the early postoperative period of patients after OLT depending on the reason for liver transplantation. MATERIALS AND METHODS We retrospectively evaluated 309 OLT recipients transplanted between 2003 and 2006, including 161 women and 148 men. We analyzed the results of early postoperative rehabilitation measured by the time to full, active, erection upright after surgery. We divided the patients into 5 groups due to etiology of liver failure: group A (n = 89; mean age, 46.7 years) consisted of patients with liver cirrhosis due to hepatitis B, C, or both; group B (n = 70; mean age, 43.8 years) included patients with primary biliary cirrhosis and primary sclerosing cholangitis; group C (n = 44; mean age, 46 years) conprised patients with postalcoholic liver cirrhosis; group D (n = 23; mean age, 29.7 years) had experienced acute or subacute liver failure; and group E (n = 83; mean age, 37.4 years) had other reasons of liver failure. All patients were included in an identical rehabilitation program. RESULTS The mean time to full, active, erection upright was dependent on the reason for liver failure. The best result was observed in groups A and E (4.51 and 4.6 days, respectively), medium in groups B and C (5.3 and 5.02, respectively), and worst in group D (8.5 days). The differences between groups A, E, and D were significant. CONCLUSION The best results were obtained in groups A and E, where full, active, erection upright was achieved at 4.51 and 4.60 days respectively, and worst in group D, where it was achieved on day 8.50. These results need to be taken into account in planning the rehabilitation process for OLT patients. When analyzing the correlation between full, active, erection upright and primary diseases, one of the factors contributing to the delay needs to be assumed to be the inability to develop compensating mechanisms in the cases of acute and subacute hepatic failures, resulting from the sudden development of the disease.