Evaluation of Overall Survival and Disease-Free Survival in Patients Receiving Liver Transplantation for Hepatocellular Carcinoma and Comparison of Living Versus Deceased Donor Liver Transplants: Results of 15 Years of Experience.

OBJECTIVE: Research comparing patients who received liver transplantation (LT) for hepatocellular carcinoma (HCC) has produced varying outcomes regarding survival and disease-free survival. The objective of this study is to determine the factors that influence the disease-free and overall survivals of those who have undergone LT for HCC and to compare the outcomes of living versus deceased donor liver transplants. MATERIALS AND METHODS: We retrospectively analyzed data on patients aged 18 and above who received LT for HCC from 2006 to 2022. Patients with a follow-up period of less than 6 months and who did not meet the University of California San Francisco criteria were excluded. The data from 58 patients were analyzed. We split the patients into living donor liver transplantation (LDLT) (group 1) and deceased donor liver transplantation (DDLT) (group 2). RESULTS: The mean age was 56 ± 8.1 years. There were 49 males and 9 females. The median of the alphafetoprotein (AFP) level and model for end-stage liver disease score was 10.1 ng/mL and 11, respectively. The 1-, 3-, 5-, and 10-year disease-free survival rates were 86%, 76.5%, 76.5%, and 76.5%, respectively. The survival rates for the same periods were 94.8%, 74.9%, 70.6%, and 67.4%. The receiver operating characteristic analysis revealed that AFP > 31.8 ng/mL and a total tumor size >3.85 cm raise the likelihood of HCC recurrence post-LT. CONCLUSION: Based on the current literature, the overall survival and disease-free survival rates are influenced by factors such as AFP value, total tumor number, and total tumor diameter. In our study, the AFP value and total tumor size had an impact on the recurrence of HCC, and the survival rates were comparable on LDLT and DDLT.

Safety and Threshold Analysis of Preoperative Platelets in Right Lobe Living Donors for Liver Transplantation.

BACKGROUND: Low perioperative platelet count is a powerful independent risk factor for posthepatectomy liver failure. Usually, categorical effect of thrombocytopenia was taken into account; upper thresholds were not studied in depth, exclusively in living liver donors. METHODS: Living liver donors who underwent right hepatectomy were included. Preoperative characteristics of donors were identified and examined to predict posthepatectomy liver failure. To eliminate selection bias, one-to-one propensity score matching was performed. RESULTS: There were a total of 139 living donors and 40 (29%) donors developed posthepatectomy liver failure in the aftermath of the operation. Remnant liver volume ratio and preoperative platelet count were identified as adjustable independent risk factors (OR: 0.89 and 0.99, 95% CI: 0.79-0.99 and 0.98-0.99, respectively). After propensity score matching, odds ratio of preoperative platelet count was 0.99 (95% CI: 0.98-1.00). CONCLUSIONS: Preoperative platelet count, in addition to remnant liver volume ratio, can be used as a surrogate marker to predict the risk of posthepatectomy liver failure in living liver right lobe donors. Probability curves figured out from logistic regression analysis, in this regard, provided an explicit perspective of platelets having a decisive role on liver donor safety. Thus, remaining in safer remnant liver volume ratio limits with respect to preoperative platelet count should be addressed in safe donor selection strategies.

Impact of older age on the long-term survival in living-donor liver transplantation: A propensity score matching analysis.

BACKGROUND: Prevalence of the end-stage liver disease in the elderly patients indicating a liver transplantation (LT) has been increasing. There is no universally accepted upper age limit for LT candidates but the functional status of older patients is important in pre-LT evaluation. This study aimed to examine the impact of older age on survival after living donor liver transplantation (LDLT). METHOD: A total of 171 LDLT recipients were assessed in two groups: age ≥65 and < 65. To eliminate selection bias propensity score matching (PSM) was performed, and 56 of 171 recipients were included in this study. RESULTS: There were 20 recipients in the older group and 36 in the younger. The 1-, 3-, and 5-year survival rates were 65.0%, 60.0%, and 60.0% in group 1; 88.9%, 84.7%, and 71.4% in group 2, respectively. The 1-year survival was significantly lower in the older recipients; however, overall survival rates were similar between the groups. Of the 56 recipients, 15 (27%) deaths were observed in overall, and 11 (20%) in 1-year follow-up. The univariate regression analysis after PSM revealed that MELD score affected 1- year survival and the multivariate analysis revealed that age ≥65 years and MELD score were the predictors of 1-year survival. CONCLUSION: At first sight, before PSM, survival appeared to be worse for older recipients. However, we have shown that there were confounding effects of clinical variables in the preliminary evaluation. After the elimination of this bias with PSM, This study highlights that older recipients have similar outcomes as youngers in LDLT for long-term survival.

Serum Levels of S100ß, Neuron-Specific Enolase, Glial Fibrillary Acidic Protein in Kidney Transplant Recipients and Donors: A Prospective Cohort Study.

BACKGROUND: The aim of this study was to evaluate changes in serum levels of S100ß, neuron-specific enolase, glial fibrillary acidic protein in living donors and recipients after kidney transplantation. METHODS: We enrolled 56 patients into the study. Of these, 27 underwent donor nephrectomy (group D), and the remaining 29 underwent kidney transplantation (recipient, group R). Neuromarkers were measured in samples obtained before the procedure, on postoperative day 7, and at 1 month postoperatively. RESULTS: Postoperative kidney functions were impaired in patients who underwent living donor nephrectomy compared with their preoperative levels (P < .001), although no significant difference was observed in their neuromarkers. The postoperative delirium rating scale was also impaired after living donor nephrectomy compared with preoperative levels (P < .05). Postoperative kidney functions were improved (P < .001), and a progressive decrease in neuromarker levels (P < .05) was observed in kidney transplant recipients compared with their preoperative levels. Linear regression analysis showed a significant correlation between neuron-specific enolase, glial fibrillary acidic protein levels and kidney functions in recipients. CONCLUSION: The present study demonstrated that neuron-specific enolase and glial fibrillary acidic protein levels decrease in kidney transplant recipients and do not change in donors. This result indicated that there is no evidence of neurotoxicity in either recipients and donors in kidney transplantation.

Effect of post-perfusion hyperoxemia on early graft function in renal transplant recipients: a retrospective observational cohort study.

BACKGROUND: The effects of hyperoxemia on the transplanted grafts arouse interest nowadays, particularly intraoperative hyperoxemia, on transplant kidney function and survival in the 1-year post-operative period. AIMS: We aimed to investigate the effect of post-perfusion (5 min after perfusion) hyperoxemia on early graft function and survival in renal transplant recipients. METHODS: Two hundred forty-seven living donor kidney transplant recipients were included in the study. Patients were divided into the three groups according to their partial arterial oxygen pressure in post-perfusion blood gas samples: group 1: normoxia (n = 52, PaO2 pressure: < 120 mmHg, 103 ± 13); group 2: moderate hyperoxemia (n = 121, PaO2: 120-200 mmHg, 169 ± 21); group 3: severe hyperoxemia (n = 74, PaO2: > 200 mmHg, 233 ± 25). Graft functions (serum creatinine levels, estimated-glomerular filtration rate values, spot urine protein/creatinine ratio), survival rates, and groups' clinical outcomes were compared in the first year after transplantation. RESULTS: Graft survival rates were similar in the groups and the rate of BK virus viremia was the lowest in the group 3 (groups 1, 2, and 3: 15.4% (n = 8), 6.6% (n = 8), 1.4% (n = 1), respectively, P: 0.009). Serum creatinine and proteinuria levels were lower, and estimated-glomerular filtration rate values were higher in group 3. A negative correlation between partial arterial oxygen pressure and serum creatinine levels and a positive correlation with estimated-glomerular filtration rate value were noted. These results were confirmed by univariate and multivariate analyses. CONCLUSIONS: We demonstrated that the kidney transplant recipients with post-perfusion hyperoxemia have better early graft functions and lower BK virus viremia rates. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04420897.

Evaluation of Preoperative and Postoperative S100ß and NSE Levels in Liver Transplantation and Right Lobe Living-Donor Hepatectomy: A Prospective Cohort Study.

BACKGROUND AND AIMS: This study aimed to evaluate plasma neuron-specific enolase (NSE) and S100ß levels in orthotopic liver transplantation. MATERIALS AND METHODS: A total of 56 patients who underwent orthotopic liver transplantation were divided into 3 groups. Healthy donors (group D), end-stage liver failure (ESLF) patients (recipient, group R), and ESLF patients diagnosed with hepatic encephalopathy (HE, group HE). Prognosis, preoperative routine laboratory findings, serum NSE, and S100ß in samples obtained preoperation and first and sixth months postoperation were analyzed. RESULTS: Serum NSE and S100ß levels were significantly higher in ESLF patients compared to healthy donors, particularly during the preoperative period. There was a significant decrease in serum NSE and S100ß in ESLF patients during the postoperative measurement periods compared to preoperative levels. Serum NSE and S100ß levels measured at 3 different time points showed no significant difference between ESLF patients and ESLF patients with HE. However, the recent Model of End-Stage Liver Disease (MELD) and Child-Turcotte-Pugh (CTP) scores showed a significant correlation with serum NSE and S100ß in ESLF patients diagnosed with HE. Serum NSE and S100ß levels in healthy donors significantly increased within the first month following hepatectomy and decreased in the sixth month following surgery. CONCLUSION: Although serum NSE and S100ß levels significantly decreased with improved liver function in recipients following liver transplantation, there was no complete recovery within 6 months after surgery. The increase in serum levels of NSE and S100ß in donors measured following hepatectomy was detected to remain slightly higher in the sixth postoperative months.

A Single-Center Experience in Portal Flow Augmentation in Liver Transplantation With Prior Large Spontaneous Splenorenal Shunt.

Large portosystemic shunts may cause portal steal syndrome in liver transplantation (LT). Because of the possible devastating consequences of the syndrome, the authors recommend perioperative management of these large shunts. Fourteen adult recipients who underwent portal flow augmentation, including left renal vein ligation (LRVL), renoportal anastomosis (RPA), shunt ligation (SL), and splenic vein ligation (SVL) for large spontaneous splenorenal shunt (SSRS), are included in this study, and the results were analyzed. A total of 13 patients had a large SSRS, and in 1 patient, the large shunt was placed between the superior mesenteric vein and the right renal vein. LDLT was performed in 13 patients. LRVL (n = 5), SVL (n = 6), RPA (n = 2), SL (n = 1) were performed to the patients as graft inflow augmentation. The graft-recipient weight ratios (GRWR) were less than 0.8% in 5 patients (35.7%): 2 had LRVL, and 3 had SVL. Small-for-size syndrome (SFSS) occurred only in these 2 patients with LRVL (GRWR ≤0.8%) and, splenic artery ligation was performed for graft inflow modulation. No mortality or serious complications were reported during follow-up. We consider that in patients with large SSRS and small-for-size grafts, SVL can be performed safely and with satisfactory outcomes.

Perioperative Comparison of Preemptive and Non-Preemptive Renal Transplant Recipients.

OBJECTIVE: Preemptive transplantation cannot be performed for all patients because of the limited number of donors. This study aimed to evaluate the perioperative effects of dialysis before renal transplantation. METHODS: In this study, we retrospectively investigated 666 patients who underwent kidney transplantation at our centre. We divided patients into two groups: patients with pre-transplant dialysis (67.3%, n=448) and patients with preemptive transplant (32.7%, n=218). We carried out preoperative, intraoperative and postoperative comparisons between groups. RESULTS: No difference was observed in terms of intraoperative blood transfusion, crystalloid and colloid requirement, inotropic-vasopressor agent administration and hemodynamic parameters between the patients with pre-transplant dialysis and preemptive transplant. It was observed that dialysis requirement, delayed graft function and acute rejection development were significantly higher during the postoperative period in patients who underwent dialysis before transplantation. In patients with non-preemptive transplant, the decrease of serum creatinine levels at the first postoperative month was more prominent when compared to patients with preemptive transplant; however, that difference disappeared in the first year follow-up. No significant difference was found for serum albumin levels and proteinuria alterations of the patients in long-term follow-up. Additionally, patient and graft survival comparisons between patients with non-preemptive and preemptive transplant on three-year follow-up revealed no significant difference. CONCLUSION: We think that preemptive transplantation treatment is a better option for patients with end-stage renal failure since patients with preemptive transplantation appear to have less metabolic function impairment, complication risk and more successful outcomes in terms of cost-effectiveness.

Kyphoplasty experience in an elderly.

OBJECTIVE: Vertebral compression fractures due to osteoporosis are seen frequently. Osteoporotic compression fractures can cause severe pain, limitation of physical activities and impairment of quality of life. Kyphoplasty, a minimally invasive procedure, could be effective in many cases and can provide fast pain relief. CASE: A patient with a history of falling from a height of 8 months duration visited our pain clinic. Opioids and anti-inflammatory analgesics were administered together with physical therapy and facet joint injections with no improvement. Radiological examination of the patient showed collapse fracture of L2 and L4 vertebrae on top of severe osteoporosis. Kyphoplasty was performed at the level of L2 vertebrae followed by 50% relieve in her pain (VAS score reduction from 8 to 3) and hence she was capable to resume her daily activities. CONCLUSION: Percutaneous balloon kyphoplasty is a safe and effective procedure for the treatment of elder patient with osteoporotic vertebral compression fractures.

The role of cytochrome P450 pharmacogenomics in chronic non-cancer pain patients.

INTRODUCTION: Pharmacogenomics is the field that studies an individualized treatment approach for patients' medication regimen that can impact drug safety, productivity, and personalized health care. Pharmacogenomics characterizes the genetic differences in metabolic pathways which can affect a patient's individual responses to drug treatments. Areas covered: The various responses to pharmacological agents are mainly determined by the different types of genetic variants of the CYP450. CYP2D6 polymorphism is well known for its variation in the metabolism of drugs from many therapeutic arenas, including some analgesic drugs such as codeine, hydromorphone, oxycodone and tramadol. Allele combinations determine the phenotypic expression, characterized as either: extensive metabolizer, intermediate metabolizer, ultra-rapid metabolizer and poor metabolizer. Expert opinion: The Human Genome Project (HGP) revolutionized the future of medicine and the way health care providers approach individualized patient treatment, and chronic pain management is one of those areas. The key findings in the literature appear to be related to the CYP2D6 expression and its high polymorphism influencing the metabolism of opioid medications, and the impact of that on the patient's therapeutic outcome thus exemplifying the importance of genetic testing for CYP2D6 in the process of physician therapeutic decision making.

Endothelial dysfunction in the human umbilical artery due to preeclampsia can be prevented by sildenafil.

OBJECTIVES: We aimed to determine the effects of sildenafil in human umbilical artery preparation taken from preeclamptic or normal pregnant women, also to investigate underlying mechanisms in these effects. STUDY DESIGN: Eighteen pregnant women with preeclampsia and 18 healthy pregnant women were involved. Relaxation responses of sildenafil in presence and absence of nitric oxide (NO) synthase inhibitor, N-[omega]-nitro-L-arginine methyl ester (L-NAME), and soluble guanylyl cyclase inhibitor, 1H-[1,2,4] oxadiazolo [4,3-a]quinoxalin-1-one (ODQ), were compared between the preeclampsia group and control group. RESULTS: Sildenafil-induced relaxation responses were significantly attenuated in the presence of preeclampsia, L-NAME or ODQ, but not totally abolished. Interestingly, except with ODQ incubation, in all set of experiments maximal relaxation response was achieved by sildenafil. CONCLUSION: These data indicate that sildenafil might effect vascular responsiveness of human umbilical artery through the involvement of NO/cyclic guanosine monophosphate (cGMP)-dependent and -independent pathways. Further investigations are needed to clarify the exact mechanisms.

Different effects of different phosphodiesterase type-5 inhibitors in pre-eclampsia.

OBJECTIVES: We aimed to determine the effects of sildenafil and vardenafil in human umbilical artery preparation taken from pre-eclamptic or normal pregnant women, and also to investigate the underlying mechanisms in these effects. STUDY DESIGN: Fifteen pregnant women with pre-eclampsia and 15 healthy pregnant women were involved. Relaxation responses of sildenafil and vardenafil in the presence and absence of nitric oxide synthase inhibitor, N-[omega]-nitro-l-arginine methyl ester (l-NAME), and soluble guanylyl cyclase inhibitor, 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ), were compared between the pre-eclampsia group and the control group. RESULTS: Sildenafil induced relaxation responses were significantly attenuated in the presence of pre-eclampsia, l-NAME and QDO. Similarly, pre-eclampsia, l-NAME or ODQ incubation also shifted vardenafil-induced relaxation responses rightward. However, in all set of experiments a maximal relaxation response was achieved by vardenafil unlike sildenafil. In conclusion vardenafil seems to relax human umbilical artery stronger than sildenafil in both pre-eclamptic and normal pregnancies. CONCLUSION: These data indicate that vardenafil might affect vascular responsiveness of human umbilical artery through the involvement of NO/cGMP-dependent and independent pathways while sildenafil-induced responses were seemed to be completely NO/cGMP-dependent. Further investigations are needed to clarify the mechanisms.