The Effect of Perioperative N-acetylcysteine on the Short and Long Term Outcomes in Pediatrics Undergoing Living-Donor Liver Transplantation.

BACKGROUND: Ischemia-reperfusion injury during transplantation can cause post-operative graft dysfunction. OBJECTIVE: To assess the efficacy of N-acetylcysteine in preventing hepatic ischemia-reperfusion injury and post-transplant outcomes. METHODS: In this retrospective study on pediatrics undergoing living-donor (from one of their parents) liver transplantation, N-acetylcysteine was administered to one group (n=20) after induction in the donors until graft harvest, and in the recipients during implantation, which was maintained for 19 hours. The second group (n=20) did not receive NAC. Early allograft dysfunction was determined in the presence of alanine aminotransferase or aspartate aminotransferase ≥2000 IU/L and bilirubin ≥10 mg/dL within the first 7 days, and an international normalized ratio ≥1.6 on day 7. Data were collected from a retrospectively maintained database. RESULTS: The incidence of post-reperfusion syndrome was lower in N-acetylcysteine group compared with the other group (5% vs. 30%, p=0.037). Serum creatinine level was significantly (p=0.04) different in the N-acetylcysteine group during the second post-operative week (0.14 vs. 0.15 mg/dL). There was no significant difference in the incidence of early allograft dysfunction (21% vs. 14%, p=0.327), and the survival rate (p=0.409). CONCLUSION: Peri-operative infusion of N-acetylcysteine in both donor and recipient would effectively prevent post-reperfusion syndrome and renal insufficiency. However, it might not affect the early allograft dysfunction, ICU stay, and mortality. NAC increases the chance of re-operation due to non-surgical bleeding in the first post-operative day.

Liver Transplantation in Hepatocellular Carcinoma: Experiences from the Shiraz Transplant Center.

BACKGROUND: Studies evaluating liver transplantation (LT) in hepatocellular carcinoma (HCC) in the Middle East have been scarce, mainly due to intricacy of this type of surgery. OBJECTIVE: In here we report our experiences with LT among patients with HCC cirrhosis.Methods: All patients who underwent LT with primary diagnosis of HCC older than 18 years old, during 2004 to 2019, were initially included in our study. RESULTS: Overall, 124 patients entered our study, among which majority were males (86.3%). Mean (SD) age of patients was 53.1±10.6 years old. Most common underlying liver diseases were HBV (55.6%) and HCV infections (12.1%). Mean MELD score of patients was 18±5.5. Child-Pugh score of most patients was class B (50%). Mean (SD) duration of hospitalization was 12.1±3.5 days. Patients were followed for a median of 32 (9, 62) months. The most common causes of death were recurrence of HCC (47.7%) and sepsis (34.1%). Median (IQR) duration to recurrence and death were 18 (4, 34) months and 17.5 (5.7, 44.5) months, respectively. One-year survival (89%, 86.4%, and 63.2%, respectively) (p=0.011) and one-year DFS (89%, 86.4%, and 57.9%, respectively) (p=0.001) was significant different between those who were selected based on the Milan, UCSF and extended criteria. CONCLUSION: Our study provides valuable experiences on LT and HCC from one of the largest LT centers in the world. Accordingly, we found that the Milan criterion provides the best survival compared to the UCSF and our extended criteria for patient selection.

Virtual Crossmatching in Kidney Transplantation, Shiraz Experience in Development of a Web-Based Program.

BACKGROUND: Kidney transplantation can increase survival and quality of life in patients with end-stage renal disease. In any allocation system, the crossmatch test plays an essential role in donor-recipient compatibility. OBJECTIVE: In this study, we aim to test the benefits of a web-based program that captures HLA antibody analyses and provides a report to allow fast and accurate virtual crossmatches. METHODS: One hundred potential recipients in the waiting list of renal transplants were selected. The included patients all had a complete HLA antibody profile. Also, 10 potential donors from previous kidney transplants (2020), with available HLA typing results for A, B, and DR locus, were also selected. A comparison was made between 100 recipients against ten potential donors, and virtual crossmatching (VXM) was performed by the web-based program and manually by an experienced immunologist. RESULTS: The average time for a manual VXM was 30 minutes per patient, while the virtual cross web-based program took 5 minutes per patient. In 12% of the manual VXM cases, a secondary review of data improved final results. In two manual virtual crossmatches, the VXM results had errors in matching recipient antibodies with the donor HLA typing that could affect the final decision for transplantation. CONCLUSION: In conclusion, a web-based VXM program that assesses HLA data can accurately perform a VXM with fewer human errors. It is especially true for highly sensitized candidates.

Effects of Different Cold Preservation Solutions on the Functions of Cultured Isolated Human Hepatocytes.

BACKGROUND: Hepatocyte transplantation using isolated human hepatocytes is an alternative source that can be used for the treatment of metabolic diseases and acute liver failure as a time bridge to liver transplantation. These cells can also be used for bioartificial liver systems and in vitro study of drug toxicity. OBJECTIVE: To determine which cold preservation solution is better maintain the liver function. METHODS: We prepared 4 cold preservation solutions made of different combination of antioxidants, chelating, membrane protective, and anti-apoptotic agents as well as inhibitor of cyclophilin D. For hepatocyte isolation, we used livers obtained from unused deceased donor livers and the liver of patients with Crigler-Najjar syndrome who were candidates of partial liver transplantation. After culture and cold preservation, the level of albumin, and urea production were measured as indices of liver functionality. RESULTS: We found that albumin production significantly decreased after cold preservation in solution 1. There was no significant difference in urea production after cold preservation in solution 1 compared with control 24 h. No significant differences in albumin production were found after cold storage in solution 2 and solution 4 compared with control 24 h. Urea production significantly decreased after cold storage in solutions 2 and 4 compared with control 24 h. As a whole albumin and urea production were significantly decreased after cold preservation. Although albumin and urea production were decreased after cold preservation, but the results of albumin production of two solutions were not significantly different from that of the control group (p=0.109 and 0.951). CONCLUSION: Cold preservation of cultured human hepatocytes in solution 2 and solution 4 could maintain the function of albumin production better than other cold preservation solutions in our experiments; solution 1 was more effective on urea production of cultured human hepatocytes at 4 °C for 24 h. To determine if these hepatocytes are suitable candidates for transplantation, further studies should be performed.

Donors' Quality of Life after Living Donor Liver Transplantation: Shiraz Organ Transplant Center Experience.

BACKGROUND: Probable effects of living donor liver transplantation on the wellbeing of the donor and psychological difficulties are necessary to be understood. OBJECTIVE: To assess the quality of life of living donors after liver donation. METHODS: 140 living donors who underwent hepatectomy between 2012 and July 2015 were enrolled in this study. Donors were asked to complete the Short Form 36-question Health Survey (SF-36) through face to face or by telephone interview. RESULTS: The mean±SD age of donors at transplantation was 32.1±7.3 years; 83 (59.3%) of donors were female. 134 (95.7%) were married. The mean±SD BMI was 23.8±3.5 (kg/m2). "Mother-to-child" was the most frequent relationship (n=79, 56.4%). 22 (15.7%) complications were reported by participants. The mean±SD score of Physical Component Summary and Mental Component Summary were 48.8±14.6 and 50.1±6.9, respectively. CONCLUSION: Most living donors sustain a near average quality of life post-donation. It seems that living donation does not negatively affect the quality of life.

The Effects of Cold Preservation Solutions Supplemented with UDCA and α-Lipoic Acid on the Viability and Function of Isolated Human Hepatocytes.

BACKGROUND: Liver transplantation is the only treatment for end-stage and genetic liver diseases. The main burden of this treatment is the shortage of both living and cadaveric liver donors. An alternative treatment is using liver cell transplantation, which can be obtained from unused livers for transplantation. These hepatocytes should be kept ready in viable and functional situation in a frozen state to be instantly used when they would be needed. In our previous experience, we had isolated hepatocytes from unused livers. OBJECTIVE: To find a preserving solution for increasing viability and function of the isolated hepatocytes that are stored to be transplanted. METHODS: 9 cadaveric donor livers, which were not used for transplantation due to various causes such as severe steatosis, were selected to isolate hepatocytes. Various cold storage solutions were tried to find the best temperature for more viability and functionality for preservation of hepatocytes. University of Wisconsin (UW) solution and Williams E media were used as control media. 2 anti-apoptotic and anti-oxidative solutions, i.e., α-lipoic acid and ursodeoxycholic acid (UDCA), were used as cold preservatives solutions. The numbers of viable hepatocytes were estimated by trypan blue method; the functionality was assessed by the cells ability to produce urea. RESULTS: The highest number of viable and functional hepatocytes was obtained from freshly isolated cells. However, after preservation, the number of these viable hepatocytes and their functionality were not significantly different in cold storage solutions comparing to the control media used. Functionality of the isolated hepatocytes stored in UW with and without UCDA solution was similar to freshly isolated hepatocytes. CONCLUSION: Preservatives with anti-apoptotic and antioxidant activity could not increase the number of viable hepatocytes. Functionality of cold storing hepatocytes could be preserved similar to freshly isolated hepatocytes by UW solution with and without UCDA.

Comparison of Human Mesenchymal Stem Cells Derived from Various Compartments of Human Adipose Tissue and Tunica Adventitia Layer of the Arteries Subsequent to Organ Donation.

BACKGROUND: Mesenchymal stem cells are one of the most interesting cell sources used in regenerative medicine. OBJECTIVE: In the present study, we isolated and characterized the mesenchymal stem cells from various compartments of human adipose tissue and tunica adventitia layer of the arteries. METHODS: Tissue explant culture was done from various compartments of the human adipose tissue and tunica adventitia layer of the arteries, including adipose tissue far from the vessels, perivascular tissues that are completely attached to the vessels, and tunica adventitia layer of the arteries. After the cell culture, characterization of the cells was determined at 3rd-5th passages. Flow cytometry was performed for antigen expression analysis of CD34, CD45, CD44, CD90, CD29, CD73, and CD105. For the evaluation of cell differentiation potential, adipogenic and osteogenic differentiation was conducted under appropriate protocols. RESULTS: The cells were positive for CD44, CD90, CD29, and CD73 and negative for CD34, CD45, and CD105. Adipogenic and osteogenic differentiation potentials were different among the cells from various compartments. The cells derived from perivascular tissue demonstrated better adipogenic and osteogenic differentiation. CONCLUSION: It is essential to characterize the cells from different tissues and compartments for different purposes in regenerative medicine.

Blood Product Transfusion in Liver Transplantation and its Impact on Short-term Survival.

BACKGROUND: Estimation of the amount of blood products required during liver transplantation can help provision of adequate blood supply, minimize transfusion-associated complications, and plan for preventive measures in high risk patients. OBJECTIVE: To investigate independent predictors of peri-operative blood product transfusion and its impact on short-term survival of liver transplant recipients. METHODS: In a cross-sectional study, old charts of patients who underwent liver transplantation between March 2003 and March 2013 at Namazi Hospital, Shiraz, Iran, were reviewed. The mean amount of blood product utilized during surgery and hospital stay and the related factors, including demographic characteristics, pre-transplant laboratory data, pre-transplant clinical data, operation data, and post-transplantation data were recorded. RESULTS: We studied 1198 patients who underwent liver transplantation. The mean±SD amounts of red blood cells, fresh frozen plasma, and platelet transfusion during surgery and hospital stay were 2.67±3.5, 2.06±3.8, and 1.6±3.8 units, respectively. The mortality rate was significantly higher in patients who received high amounts of blood products (p<0.001). The mean amount of blood products' utilized during operation was significantly (p<0.001) decreased from 2003 to 2013.The mean amount of packed cell usage during operation and hospital stay was significantly (p<0.001) correlated with age, technique of surgery, serum albumin level, cirrhosis, blood urea nitrogen, length of operation, and prothrombin time. CONCLUSION: Pre-operative factors may predict blood transfusion requirements in patients undergoing liver transplantation. Therefore, evaluation of patients before operation should be considered to provide adequate blood supply and minimize transfusion-associated complications. Understanding pre-operative factors associated with rate of transfusion may help us to best utilize the limited available blood resources.

Classification Models to Predict Survival of Kidney Transplant Recipients Using Two Intelligent Techniques of Data Mining and Logistic Regression.

Kidney transplantation is the treatment of choice for patients with end-stage renal disease (ESRD). Prediction of the transplant survival is of paramount importance. The objective of this study was to develop a model for predicting survival in kidney transplant recipients. In a cross-sectional study, 717 patients with ESRD admitted to Nemazee Hospital during 2008-2012 for renal transplantation were studied and the transplant survival was predicted for 5 years. The multilayer perceptron of artificial neural networks (MLP-ANN), logistic regression (LR), Support Vector Machine (SVM), and evaluation tools were used to verify the determinant models of the predictions and determine the independent predictors. The accuracy, area under curve (AUC), sensitivity, and specificity of SVM, MLP-ANN, and LR models were 90.4%, 86.5%, 98.2%, and 49.6%; 85.9%, 76.9%, 97.3%, and 26.1%; and 84.7%, 77.4%, 97.5%, and 17.4%, respectively. Meanwhile, the independent predictors were discharge time creatinine level, recipient age, donor age, donor blood group, cause of ESRD, recipient hypertension after transplantation, and duration of dialysis before transplantation. SVM and MLP-ANN models could efficiently be used for determining survival prediction in kidney transplant recipients.

Prevalence of Metabolic Syndrome in Liver Transplant Recipients in Iran.

BACKGROUND: Metabolic syndrome (MetSx) is common among liver transplant recipients. It contributes to morbidity and mortality. OBJECTIVE: To determine the prevalence of MetSx in patients undergoing liver transplantation (LTx) in Iran. METHODS: 202 liver transplant recipients of both sexes completed this study. Relevant information including age, sex, the underlying disease, systolic and diastolic blood pressure, waist circumference, fasting serum levels of blood sugar (FBS), triglyceride (TG), and HDL-cholesterol were measured. The prevalence of MetSx was evaluated at 1, 3, 6, 9, and 12 months after LTx. RESULTS: The prevalence of MetSx was 36.6% after 1 month that decreased to 28.2% after 12 months of follow-up. The lowest prevalence of MetSx (27.7%) was observed 9 months after LTx. Our data showed a decrease in TG and an increase in HDL-C level and no significant changes in blood pressure, waist circumference and FBS during the study period. CONCLUSION: The prevalence of MetSx after LTx is high when compared to the normal population. It seems that a change in diet after transplantation may affect the prevalence of MetSx.

Parents' education level and mortality and morbidity of children after liver transplantation.

BACKGROUND: So far numerous post-transplant outcome predictors have been studied to decrease the loss of resources and grafts after organ transplantation. The role of education, as a predictor, in liver transplantation outcome has so far been studied in several articles. However, in most of the studies it was evaluated as a surrogate for socioeconomic status or other variants. The absolute impact of parents' education has rarely been studied. Adult patients are their own caregivers whereas pediatric liver transplantation recipients are mostly cared by their parents. OBJECTIVE: To evaluate the effect of level of patients' education on the mortality and morbidity of pediatric liver transplant recipients. METHODS: We studied a group of 91 children who had undergone liver transplantation in our center from March 21, 2012 to July 21, 2013. In this retrospective study, patients' medical charts and questionnaire were used to collect the necessary data. Post-transplantation mortality and complications were divided into two categories: Early (<6 months after liver transplantation), and late (≥6 months after the transplantation). Parents' educational level was also categorized into 5 groups. RESULTS: Multivariate analysis of all groups showed that paternal education is an independent predictor of the late post-transplantation complications (p=0.024). Educational level of children's mothers had no significant correlation with the late post-transplantation complications (p=0.45). Neither maternal (p=0.59) nor paternal (p=0.607) education had significant effect on the late post-transplantation mortality. CONCLUSION: Paternal educational level of liver transplanted children is associated with the late post-transplantation complications.

Polymorphism of the IL-18 and CD40 genes and Liver Transplant Outcome in Iranian Patients.

BACKGROUND: Cytokines and co-stimulatory molecules are important factors determining the outcome of transplantation. OBJECTIVE: To investigate the effect of IL-18 and CD40 gene polymorphisms on the outcome of liver transplantation. METHODS: 150 liver transplant recipients were included in this study. Alleles and genotypes frequencies for IL-18 (rs1946519) and CD40 (rs1883832) were determined in 28 acutely rejected (AR group) and 122 non-acutely rejected (non-AR group) liver transplant recipients. IL-18 and CD40 gene polymorphisms were evaluated by PCR-RFLP methods. RESULTS: There were no significant associations between IL-18 and CD40 polymorphism with acute rejection in liver transplant patients. IL-18TT and TG genotypes had a significant association with rejection in women compared to men. After grouping the liver recipients according to living vs cadaver donors, a significant association was found between CC genotype of CD40 and rejection in male living donor recipients. IL-18 TG genotype had a significant association with rejection in female cadaver donor recipients. CONCLUSION: There is no correlation between all genotype and alleles of IL-80 and CD40 polymorphism and the outcome of liver transplantation. However, gender and type of donor affect the correlation between all genotype and alleles of IL-18 and CD40, and the outcome of liver transplantation.

Ex-vivo Resection and Small-Bowel Auto-transplantation for the Treatment of Tumors at the Root of the Mesentery.

BACKGROUND: Tumors involving the root of the mesentery are generally regarded as "unresectable" with conventional surgical techniques. Resection with conventional surgery may end in life-threatening complications in these patients. Ex-vivo resection and auto-transplantation avoids excessive bleeding and prevents ischemic related damage to the small intestine and other organs. OBJECTIVE: To share our experience of ex-vivo resection of the tumors with involvement of small bowel mesentery followed by small bowel auto-transplantation. METHODS: In this study, medical records of all the patients who underwent ex-vivo resection and auto-transplantation at our center were retrospectively analyzed. RESULTS: The most common indication for the procedure in our series was locally advanced pancreatic carcinoma. Our survival rate was 50% with a mean±SD follow-up of 10.1±9.8 (range: 0-26) months. Causes of early in-hospital mortality were multi-organ failure, sepsis, and cerebrovascular accident. Recurrence of disease was noted in one patient while one patient developed hepatic metastasis after 20 months of surgery. CONCLUSION: Ex-vivo resection of the tumor and auto-transplantation is the surgical treatment of choice for the locally advanced abdominal tumors involving the root of the mesentery.

Multivisceral and small bowel transplantation at shiraz organ transplant center.

BACKGROUND: Multivisceral transplantations were initially done in animal models to understand the immunological effects. Later on, in human beings, it has been considered a salvage procedure for unresectable complex abdominal malignancies. With advancement in surgical techniques, availability of better immunosuppressive drugs, and development of better post-operative management protocols, outcomes have been improved after these complex surgical procedures. OBJECTIVE: To analyze and report results of multivisceral, modified multivisceral, and small bowel transplantations done at Shiraz Organ Transplant Center, Shiraz, southern Iran. METHODS: Medical records of all patients who underwent multivisceral, modified multivisceral, and small bowel transplants were retrospectively analyzed. RESULTS: There were 18 patients. The most common indications for the procedure in our series were unresectable carcinoma of pancreas followed by short bowel syndrome. 10 patients were alive after a median follow-up of 8.7 (range: 3-32) months. The remaining 8 patients died post-operatively, mostly from septicemia. CONCLUSION: Multivisceral and small bowel transplantations are promising treatments for complex abdominal pathologies.

Multivisceral transplantation for the treatment of intra-abdominal tumors.

BACKGROUND: Some intra-abdominal or retroperitoneal tumors such as low-grade slow-growing malignancies may seem unresectable due to major vessel encasement or presence of intra-abdominal dissemination, but the slow growth rate and to some extent long life expectancy of the patients urge us to find some strategies to cure the patients or at least achieve tumor remission or symptom palliation. En bloc resection, followed by multivisceral or liver-sparing "modified" multivisceral transplantation has recently been used for treatment of these patients. RESULTS: Between May 2010 and October 2012, 3 multivisceral and 3 modified multivisceral transplantations were performed in 6 patients (aged 14 to 55 years; mean, 32 years) with some slow growing intra-abdominal malignancies (2 neuroendocrine tumors, 2 gastrointestinal stromal tumors, 1 desmoid tumor, and 1 low-grade sarcoma). All patients survived the procedure. One patient died of pancytopenia 2 months after transplantation and another died with pulmonary emboli at 4 months. The remaining 4 patients are alive without any evidence of disease recurrence. CONCLUSIONS: Although large intra-abdominal desmoid tumors, well-differentiated neuroendocrine tumors, and gastrointestinal stromal tumors are slow growing, they tend to invade locally, especially to the mesenteric root and/or celiac axis and other abdominal viscera. Complete resection followed by multivisceral transplantation could be a therapeutic option for these advanced tumors.

Association of Increased Plasma Interleukin-6 and TNF-α Levels in Donors with the Complication Rates in Liver Transplant Recipients.

BACKGROUND: Solid organ transplantation is the only definitive treatment available for patients with end-stage organ failure. Organs procured from brain-death donors are the main source of transplants. Following brain death, a burst of inflammatory reaction develops; it is characterized by increased plasma levels of cytokines. This inflammatory reaction has been associated with increased early allograft dysfunction. OBJECTIVE: In this study, we test if the increased inflammatory response in brain-death donors is associated with more recipient complications. METHODS: We prospectively recruited 38 consecutive brain-death donors admitted to the intensive care units (ICUs) of Shiraz University of Medical Sciences. Following the declaration of brain death, the demographics data on donor and recipient characteristics and cause of brain death were recorded. The post-liver transplant complications in recipients were stratified according to the Clavien classification. Plasma levels of cytokines IL-6, IL-2, and TNF-α were measured using enzyme linked immunosorbent assay (ELISA) kits, in all donors before organ procurement. RESULTS: The mean (range) age of donors was 44 (16-74) years. Trauma due to car accident was the most common cause of brain death (79%). The post-liver transplant complications occurred in 19 (50%) recipients. The mean±SD plasma TNF-α concentration was significantly (p<0.001) higher in recipients with grade 1-3 post-transplant complications (68.33±27.74 pg/mL) than those without complication (22.09±4.14 pg/mL). Recipients with complications had also a significantly (p=0.001) higher mean±SD donor plasma concentration of IL-6 (1009±375.5 pg/mL) compared to those without complications (779±202 pg/mL). No significant differences was observed between the two groups in respect to IL-2 concentration (0.295±0.333 vs 0.285±0.342 U/mL, p=0.207). Six recipients died of complications (grade5), in whom no correlation could be found with donor plasma cytokine concentrations. CONCLUSION: Higher plasma concentrations of IL-6 and TNF-α in donors before organ procurement, are associated with more post-operative complications in liver transplant recipients.

Late development of pancreatitis following gunshot trauma, a case report.

BACKGROUND: Gunshot trauma to the pancreatic duct mainly have been published from wartime experiences, but bullet injury in these cases has lead to pancreatic duct disruption, not obstruction. We report a case of chronic pancreatitis which is presented 27 years following pancreatic duct obstruction due to bullet injury during wartime, which successfully treated. He was a 45-year-old man came with chronic epigastric abdominal pain. Physical examination was suggestive of pancreatitis and laboratory data confirmed the diagnosis. Imaging studies revealed a metallic object in main pancreatic duct. He carefully treated with pancreatic head resection and pancreaticojejunal anastomosis.

Isolated renal mucormycosis after liver transplantation:an unusual case report.

Mucormycosis is a rare complication of immunosuppression. Most of the reported cases have been rhinocerebral or disseminated. Isolated renal involvement is extremely rare and until now less than 30 patients have been reported in the English literature. Isolated renal mucormycosis with renal artery rupture in a liver transplant patient has not been reported so far. Herein we report an extremely rare case of isolated renal mucormycosis in a liver transplant patient who was successfully treated with nephrectomy.

En-bloc Transplantation: an Eligible Technique for Unilateral Dual Kidney Transplantation.

BACKGROUND: Kidney transplantation is the best available treatment for patients with end-stage renal disease. OBJECTIVE: To evaluate the en bloc anastomosis technique for unilateral dual kidney transplantation (DKT). METHODS: From May to October 2011, 5 patients (4 women and 1 man) with mean age of 31.8 years underwent unilateral DKT with this technique in which distal end of the aorta and proximal end of inferior vena cava (IVC) were closed with running sutures. Then, proximal end of the aorta and distal end of the IVC were anastomosed to internal (or external) iliac artery and external iliac vein, respectively. RESULTS: Post-operative course was uneventful. No vascular and urologic complications developed; all patient had acceptable serum creatinine at discharge time and up of 2-6 months of post-operation follow up. CONCLUSION: Unilateral DKT is a safe method for performing DKT. The proposed en bloc anastomosis can improve the outcome of the graft by reducing the cold ischemia and the operation time.