Ian Alwayn

Evidence-Based Approach to Cholangiocarcinoma: A Systematic Review of the Current Literature

adjusted mortality rate increased from 0.07 per 100,000 in 1973 to 0.69 per 100,000 in 1997, with average age at presentation in the 7th decade of life and male-to-female ratio of 1.5. 9 Extrahepatic CC In the United States, age-adjusted incidence of extrahepatic CC (ECC) is 1.2 per 100,000 in men and 0.8 per 100,000 in women 10 and has decreased by 14% compared with two decades earlier. ECC usually present in the 7th decade of life.

Safety and effectiveness of ezetimibe in liver transplant recipients with hypercholesterolemia

Hypercholesterolemia is a common problem among transplant recipients. Despite package‐insert warnings about the potential side effects of the use of statins in patients with chronic liver disease, they are often prescribed for liver transplant recipients. Unlike statins, ezetimibe acts through inhibition of enterohepatic recirculation of lipids. We report the effectiveness and safety of ezetimibe among liver transplant recipients because this has been evaluated previously only in kidney and heart transplant patients. A consecutive cohort of 25 liver graft recipients with serum low‐density lipoprotein (LDL) levels > 100 mg/dL (2.5 mmol/L) after a mean (±standard deviation) of 55 ± 21 months following liver transplantation received ezetimibe (10 mg orally every day) for at least 6 months. Serum lipid profiles, liver and renal function tests, and dosages and blood levels of the immunosuppression drugs at baseline, 3 months, and 6 months were prospectively collected. The overall mean age was 58 ± 12 years, and 56% were males. Statin therapy and fibrates were already being used in 32% and 20% of recipients for elevated LDL and/or triglycerides, respectively. The immunosuppression regimen included cyclosporine in 48% of subjects, tacrolimus in 32%, sirolimus in 48%, and mycophenolate mofetil in 44%; only 12% were on oral prednisone with a maximum daily dose of 5 mg. After ezetimibe was started, an 18% reduction in LDL values was observed [at baseline, 147 ± 35 mg/dL (3.8 ± 0.9 mmol/L), and at 6 months, 120 ± 31 mg/dL (3.1 ± 0.8 mmol/L); P = 0.010]. After 6 months, an additional 32% achieved the target LDL level of <100 mg/dL. None of the remaining variables, including immunosuppression drug levels, varied significantly during ezetimibe therapy. None of the subjects required adjustments in their pharmacological dosages. One discontinued ezetimibe 3 months later because of cost, 2 subjects had minimal nausea, 1 subject had myalgias without a rise in creatine phosphokinase, and 1 subject had a transient elevation (3‐5 times) in liver enzymes from baseline with increases in the total and indirect bilirubin levels. In conclusion, among liver transplant recipients, hypercholesterolemia can be effectively treated with ezetimibe with few side effects and no interaction with immunosuppressive regimens. Liver Transpl 15:504–508, 2009.

The impact of vascular anastomosis time on early kidney transplant outcomes

BackgroundMost studies have found cold ischemic time to be an important predictor of delayed graft function in kidney transplantation. Relatively less is known about the warm time associated with vascular anastomosis and early outcomes.MethodsA retrospective cohort of 298 consecutive solitary deceased donor kidney recipients from January 2006 to August 2012 was analyzed to examine the association between anastomosis time and delayed graft function (need for dialysis) and length of hospital stay.ResultsDelayed graft function (DGF) was observed in 56 patients (18.8%). The median anastomosis time was 30 minutes (interquartile range 24, 45 minutes). Anastomosis time was independently associated with DGF in a multivariable, binary logistic regression analysis (odds Ratio (OR) 1.037 per minute, 95% CI 1.016, 1.057, P = 0.001). An anastomosis time >29 minutes was also associated with a 3.5 fold higher (OR 3.5, 95% CI 1.6, 7.3, P = 0.001) risk of DGF. Median days in hospital was 9 (interquartile range 7, 14 days). Every 5 minutes of longer anastomosis time (0.20 days per minute, 95% CI 0.13, 0.27, P <0.001) was associated with 1 extra day in hospital in a multivariable linear regression model. An anastomosis time >29 minutes was associated with 3.8 (95% CI 1.6, 6.0, P <0.001) more days in hospital.ConclusionAnastomosis time may be an underappreciated but modifiable variable in dictating use of hospital resources. The impact of anastomosis time on longer term outcomes deserves further study.

Optimizing left-sided live kidney donation: Hand-assisted retroperitoneoscopic as alternative to standard laparoscopic donor nephrectomy

Laparoscopic donor nephrectomy (LDN) is less traumatic and painful than the open approach, with shorter convalescence time. Hand‐assisted retroperitoneoscopic (HARP) donor nephrectomy may have benefits, particularly in left‐sided nephrectomy, including shorter operation and warm‐ischemia time (WIT) and improved safety. We evaluated outcomes of HARP alongside LDN. From July 2006 to May 2008, 20 left‐sided HARP procedures and 40 left‐sided LDNs were performed. Intra and postoperative data were prospectively collected and analysis on outcome of both techniques was performed. More female patients underwent HARP compared to LDN (75% vs. 40%, Pu2003=u20030.017). Other baseline characteristics were not significantly different. Median operation time and WIT were shorter in HARP (180 vs. 225u2003min, Pu2003=u20030.002 and 3 vs. 5u2003min, Pu2003=u20030.007 respectively). Blood loss did not differ (200u2003ml vs.150u2003ml, Pu2003=u20030.39). Intra and postoperative complication rates for HARP and LDN (respectively 10% vs. 25%, Pu2003=u20030.17 and 5% vs. 15%, Pu2003=u20030.25) were not significantly different. During median follow‐up of 18u2003months estimated glomerular filtration rates in donors and recipients and graft‐ and recipient survival did not differ between groups. Hand‐assisted retroperitoneoscopic donor nephrectomy reduces operation and warm ischemia times, and provides at least equal safety. Hand‐assisted retroperitoneoscopic may be a valuable alternative for left‐sided LDN.

Hand-assisted retroperitoneoscopic versus standard laparoscopic donor nephrectomy: HARP-trial

BackgroundTransplantation is the only treatment offering long-term benefit to patients with chronic kidney failure. Live donor nephrectomy is performed on healthy individuals who do not receive direct therapeutic benefit of the procedure themselves. In order to guarantee the donors safety, it is important to optimise the surgical approach. Recently we demonstrated the benefit of laparoscopic nephrectomy experienced by the donor. However, this method is characterised by higher in hospital costs, longer operating times and it requires a well-trained surgeon. The hand-assisted retroperitoneoscopic technique may be an alternative to a complete laparoscopic, transperitoneal approach. The peritoneum remains intact and the risk of visceral injuries is reduced. Hand-assistance results in a faster procedure and a significantly reduced operating time. The feasibility of this method has been demonstrated recently, but as to date there are no data available advocating the use of one technique above the other.Methods/designThe HARP-trial is a multi-centre randomised controlled, single-blind trial. The study compares the hand-assisted retroperitoneoscopic approach with standard laparoscopic donor nephrectomy. The objective is to determine the best approach for live donor nephrectomy to optimise donors safety and comfort while reducing donation related costs.DiscussionThis study will contribute to the evidence on any benefits of hand-assisted retroperitoneoscopic versus standard laparoscopic donor nephrectomy.Trial RegistrationDutch Trial Register NTR1433

Prolonged warm ischemia time is associated with graft failure and mortality after kidney transplantation.

Warm ischemia time is a potentially modifiable insult to transplanted kidneys, but little is known about its effect on long-term outcomes. Here we conducted a study of United States kidney transplant recipients (years 2000-2013) to determine the association between warm ischemia time (the time from organ removal from cold storage to reperfusion with warm blood) and death/graft failure. Times under 10 minutes were potentially attributed to coding error. Therefore, the 10-to-under-20-minute interval was chosen as the reference group. The primary outcome was mortality and graft failure (return to chronic dialysis or preemptive retransplantation) adjusted for recipient, donor, immunologic, and surgical factors. The study included 131,677 patients with 35,901 events. Relative to the reference patients, times of 10 to under 20, 20 to under 30, 30 to under 40, 40 to under 50, 50 to under 60, and 60 and more minutes were associated with hazard ratios of 1.07 (95% confidence interval, 0.99-1.15), 1.13 (1.06-1.22), 1.17 (1.09-1.26), 1.20 (1.12-1.30), and 1.23 (1.15-1.33) for the composite event, respectively. Association between prolonged warm ischemia time and death/graft failure persisted after stratification by donor type (living vs. deceased donor) and delayed graft function status. Thus, warm ischemia time is associated with adverse long-term patient and graft survival after kidney transplantation. Identifying strategies to reduce warm ischemia time is an important consideration for future study.

Epidermal Growth Factor Receptor–Specific Nanoprobe Biodistribution in Mouse Models

Nanotechnology offers a targeted approach to both imaging and treatment of cancer, the leading cause of death worldwide. Previous studies have found that nanoparticles with a wide variety of coatings initiate an immune response leading to sequestration in the liver and spleen. In an effort to find a nanoparticle platform which does not elicit an immune response, we created 43 nm and 44 nm of gold and silver nanoparticles coated with biomolecules normally produced by the body, α-lipoic acid and the epidermal growth factor (EGF), and have used mass spectroscopy to determine their biodistribution in mouse models, 24 h after tail vein injection. Relative to controls, mouse EGF (mEGF)-coated silver and gold nanoprobes are found at background levels in all organs including the liver and spleen. The lack of sequestration of mEGF-coated nanoprobes in the liver and spleen and the corresponding uptake of control nanoprobes at elevated levels in these organs suggest that the former are not recognized by the immune system. Further studies of cytokine and interleukin levels in the blood are required to confirm avoidance of an immune response.

Active video gaming in patients with renal transplant: a pilot study

BackgroundPatients with renal transplant are at higher risk of mortality from cardiovascular disease (CVD) compared with the general population. Physical activity has been shown to reduce the risk of CVD mortality in these patients. Unfortunately, barriers such as the harsh Canadian climate prevent patients from engaging in and harvesting the health benefits of physical activity. This pilot study explored active video gaming (AVG) as a way for patients with renal transplant to obtain physical activity and examined its effect on their functional status and quality of life (QOL).Main textWe recruited nine patients for an 8-week prospective pilot study. All patients received a Microsoft Xbox 360™ video gaming console, a Microsoft Kinect™ sensor, and the video game Your Shape Fitness Evolved 2012. Assessment of each participant before and after the intervention included blood pressure measures, a 6-minute walk test, and the Godin Leisure Time Questionnaire (GLTQ). We analyzed all nine patients at the end of the 8-week study period, and found no changes in blood pressure or GLTQ scores. However, there was a significant increase in the 6-minute walk distance (Pu2009=u20090.022), which represented a consistent increase for most patients (correlationu2009=u20090.977). In addition, participants over the age of 45xa0years (nu2009=u20094) were more likely to use the AVG system (Pu2009=u20090.042).ConclusionAVG has the potential to improve the functional status in patients with renal transplant. Further research is required to corroborate the full health benefits of AVG in this patient population.

Human leukocyte antigen, allele, and eplet mismatches in liver transplantation; observations from a small, single center cohort

BACKGROUNDnThe impact of human leukocyte antigen (HLA) matching on outcomes in liver transplantation is controversial. Varying levels of HLA matching resolutions were examined in a uniform patient population with no pre-transplant DSA from a small, single center cohort.nnnMETHODSnRetrospective chart review from a single center yielded 131 patients, 67 of which were confirmed to be DSA negative, all of which received induction immunotherapy and post-operative immunosuppression. HLA typing was achieved by sequence specific oligonucleotide probe (SSOP) method using LABType® kits. Eplet mismatch analysis was conducted using HLAMatchMaker software.nnnRESULTSnThe mean number of HLA-A antigen mismatches was significantly higher in patients experiencing acute rejection (1.8 vs 1.6, pu202f=u202f0.006). Rejection patients more frequently possessed two HLA-A mismatches compared to their non-rejection counterparts (77% vs 43%, pu202f=u202f0.071). Patient survival was found to be non-significantly decreased in patients with a higher eplet mismatch load at the HLA-A locus (pu202f=u202f0.155). No other loci were found to be predictive.nnnCONCLUSIONnIn conclusion, HLA mismatches were found to increase acute rejection and be associated with decreased patient survival. The outcomes of this study suggest an involvement of HLA-A locus mismatches in predicting liver transplant rejection and patient survival.

Surgical Drains Do Not Decrease Complication Rates But Are Associated with a Reduced Need for Imaging After Kidney Transplant Surgery

BACKGROUNDnPerigraft collections and wound complications are common after kidney transplantation. The aim of this study was to determine whether intraoperative drain placement had an effect on the risk of these complications.nnnMATERIAL AND METHODSnAdult patients who underwent kidney transplantation in our center between January 2006 and December 2014 were included. Information regarding absence/presence of drain, imaging studies, and complications (perigraft collection and wound complications) were collected. The effect of drains on outcomes was analyzed using logistic regression after adjustment for baseline characteristics.nnnRESULTSnBaseline characteristics were similar for drain (n=374) and no drain (n=283) groups. Forty-eight percent (n=317) of the patients were imaged. Fewer patients with a drain (40%) were imaged to diagnose a perigraft collection compared to those without a drain (60%, p<0.001). Perigraft collections and wound complications were detected in 28% (n=186) and 14% (n=90) of the cohort, respectively. Presence of a drain was associated with a significantly lower rate of perigraft collections (odds ratio 0.62, 95% CI [0.43-0.88], p=0.011). However, risk of wound complications was similar for those with a drain versus without a drain (odds ratio 0.67, 95% CI 0.42-1.07, p=0.096). Among the 225 patients with a complication, the subsequent intervention rate was the same for those with or without a drain (adjusted odds ratio 1.23, 95% CI 0.61-2.46. p=0.562).nnnCONCLUSIONSnDrain placement is not associated with a significant reduction in wound complications following kidney transplant and does not reduce the risk of clinically significant perigraft collections. Since it is associated with reduced need for imaging to diagnose collections, it has the potential to reduce transplant costs.