The Largest Single Center Report on Pediatric Liver Transplantation: Experiences and Lessons Learned.

OBJECTIVE: We described our experiences on pediatric liver transplantation (LT) from the largest LT center in the world termed the Shiraz Transplant Center. BACKGROUND: After the first successful pediatric LT in 1967, pediatric LT has become the routine treatment for children with liver failure worldwide. METHODS: Data on a total of 1141 pediatric cases of LT were collected. Specifics on baseline and anthropometric characteristics, clinicopathology, prognosis of recipients of LT, and donor characteristics are reported. RESULTS: Mean age of patients was 7.83 ±â€Š5.55 years old. Most common etiologies for LT were biliary atresia (15.9%), progressive familial intrahepatic cholestasis (13.4%), and Wilson's disease (13.3%), respectively.Whole organs, living donor grafts, and split grafts were used in 47.9%, 41%, and 11.1% of patients, respectively. In-hospital complications were seen among 34.7% of patients and the most common complications were infections (26.8%), bleeding (23.4%), and vascular complications (18%).Median (interquartile range) model for end stage liver disease score was 20 (15, 25). Main causes of death among patients were sepsis (35.2%), followed by post-transplantation lymphoproliferative diseases (10.5%), and primary nonfunction of liver (9%).Patient survival showed improvement over the years (1-year survival of 73.1%, 83.4%, and 84.4%, 2-year survival of 65.2%, 77.1%, and 78.7%, 5-year survival of 58.2%, 72%, and 77.8% for 1997-2007, 2007-2013, and 2013-2019, respectively; P < 0.001). CONCLUSIONS: This is the largest single-center report on pediatric LT in literature which provides valuable experiences in pediatric LT.

Portal vein thrombosis in patients with liver cirrhosis and its impact on early and long-term outcomes after liver transplantation.

AIM: Portal vein thrombosis (PVT) is a common complication amongst patients with liver cirrhosis. The PVT risk factors and its impact on post liver transplant outcome has not been well defined, yet. This study aimed to investigate PVT prevalence, its risk factors and influence on early and long-term outcomes after liver transplantation. METHODS: Adult (>18 years) patients with liver cirrhosis undergoing liver transplantation between March 2013 to March 2015 were included. Presence or absence of PVT was recorded at transplant. PVT risk factors in patients with liver cirrhosis and its impact on early and long-term outcomes were analysed. RESULTS: Portal vein thrombosis was diagnosed in 174 patients (17.3%). Large oesophageal varices (grade II and III vs grade I) (OR: 2.5; 95% CI: 1.46-4.26; P = 0.001), diabetes mellitus before transplantation (OR: 2.03; 95% CI: 1.13-3.64; P = 0.017) and cryptogenic-NASH (OR: 1.36; 95% CI: 1.08-1.72; P = 0.008) as a cause of underlying liver disease were the independent risk factors for PVT. PVT (OR: 2.05; 95% CI: 1.10-3.81; P = 0.023) was an independent predictor of early (within 90 days) posttransplant mortality, but did not influence long-term survival. CONCLUSION: Portal vein thrombosis prevalence is high in pretransplant period. NASH related cirrhosis and diabetes mellitus might be risk factors for PVT. More intense screening of these patients for PVT is warranted.

Liver transplantation as a definitive treatment for familial hypercholesterolemia: A series of 36 cases.

FH is a genetic disorder characterized by an increase in serum LDL and total cholesterol values. The afflicted patients are at increased risk of premature atherosclerosis and myocardial infarction. Different treatment modalities are present, including pharmacological agents and surgical procedures. The most effective method of therapy in refractive cases is liver transplantation. Herein, we report our experience on 36 cases of patients with FH undergoing liver transplantation in our center, the main referral center of liver transplantation in Iran. The clinical findings, hospital courses, post-operative complications, and patient follow-up are also described.

Primary pure squamous cell carcinoma of gallbladder presenting as acute cholecystitis.

Squamous cell carcinoma of the gallbladder is rare and constitutes only 0.5-3% of all malignancies of this organ. Most of the reported cases have had a component of adenocarcinoma. We report a 70-year-old man who presented with acute onset right upper quadrant pain. He operated on based on a presumptive diagnosis of acute cholecystitis according to clinical and ultrasonographic findings. Histopathological examination of the infiltrating mass of the gallbladder revealed well differentiated keratinized squamous cell carcinoma invading full wall thickness. Thorough evaluations revealed no other primary site for the tumor. Pure primary squamous cell carcinoma of the gallbladder is rarely reported. Clinicians and pathologists must be aware of its vague clinical presentations.

Nonalcoholic Steatohepatitis Is the Most Rapidly Growing Indication for Liver Transplantation in Iranian Patients.

OBJECTIVES: Nonalcoholic fatty liver disease is a rapidly growing disease and is hypothesized to become the most common cause of liver cirrhosis in the near future. This study aimed to investigate trends of nonalcoholic steatohepatitis as an indication for liver transplant in Iranian patients. MATERIALS AND METHODS: Liver transplant data from all adult patients (age > 18 y) who had undergone liver transplant between 1993 and 2017 at the Shiraz Organ Transplant Center (Shiraz, Iran) were reviewed. Underlying liver diseases leading to liver transplant were stratified according to year of transplant, and trends of increase or decline were analyzed. Kaplan-Meier curves were used for analysis of posttransplant survival of patients with nonalcoholic steatohepatitis and patients with modified nonalcoholic steatohepatitis. RESULTS: We evaluated 3184 liver transplant patients. Of these, 112 patients with biopsy-proven nonalcoholic steatohepatitis underwent liver transplant up to the end of 2017. Mean age of patients was 52.86 ± 9.01 years in those with nonalcoholic steatohepatitis and 51.73 ± 7.91 years in those with modified nonalcoholic steatohepatitis (P > .05).The prevalence of nonalcoholic steatohepatitis as an indication for liver transplant was 0.8% in 2011, 0.36% in 2012, 1.9% in 2013, 4.01% in 2014, 2.89% in 2015, 6.65% in 2016, and 9.97% in 2017. The prevalence of modified nonalcoholic steatohepatitis was 2.4% in 2011, 2.88% in 2012, 2.71% in 2013, 2% in 2014, 2.17% in 2015, 2.13% in 2016, and 2.28% in 2017. We found that nonalcoholic steatohepatitis as a cause of liver transplant increased significantly during recent years (P < .001). CONCLUSIONS: Nonalcoholic steatohepatitis is a rapidly growing indication for liver transplant among Iranian patients. Health care providers should consider programs for prevention and early diagnosis of patients with nonalcoholic steatohepatitis for proper treatment.

Predictors of Death in the Liver Transplantation Adult Candidates: An Artificial Neural Networks and Support Vector Machine Hybrid-Based Cohort Study.

Background: Model for end-stage liver disease (MELD) is currently used for liver transplantation (LT) allocation, however, it is not a sufficient criterion. Objective: This current study aims to perform a hybrid neural network analysis of different data, make a decision tree and finally design a decision support system for improving LT prioritization. Material and Methods: In this cohort follow-up-based study, baseline characteristics of 1947 adult patients, who were candidates for LT in Shiraz Organ Transplant Center, Iran, were assessed and followed for two years and those who died before LT due to the end-stage liver disease were considered as dead cases, while others considered as alive cases. A well-organized checklist was filled for each patient. Analysis of the data was performed using artificial neural networks (ANN) and support vector machines (SVM). Finally, a decision tree was illustrated and a user friendly decision support system was designed to assist physicians in LT prioritization. Results: Between all MELD types, MELD-Na was a stronger determinant of LT candidates' survival. Both ANN and SVM showed that besides MELD-Na, age and ALP (alkaline phosphatase) are the most important factors, resulting in death in LT candidates. It was cleared that MELD-Na <23, age <53 and ALP <257 IU/L were the best predictors of survival in LT candidates. An applicable decision support system was designed in this study using the above three factors. Conclusion: Therefore, Meld-Na, age and ALP should be used for LT allocation. The presented decision support system in this study will be helpful in LT prioritization by LT allocators.

Is perioperative intravesically applied antibiotic solution effective in the prophylaxis of urinary tract infections after renal transplantation?

OBJECTIVES: To evaluate the efficacy of intravesically applied amikacin for the prophylaxis of urinary tract infections (UTIs) occurring in the first 3 months after kidney transplantation. METHODS: In a prospective, randomized, controlled trial, 200 consecutive renal transplant recipients were randomly divided into two equal groups. The bladders of the first group, the amikacin group, were filled with saline solution containing amikacin (1 g in adults and 30 mg/kg in pediatric patients) whereas the bladders of the patients of the second group, the control group, were filled with saline solution. Patients were followed up for 3 months after transplantation with urine cultures to evaluate the prevalence of posttransplantation UTIs in both groups. RESULTS: The overall incidence of UTIs was found to be significantly lower in the amikacin group (25 vs. 49%; p = 0.0007). In addition, male patients, patients with end-stage renal disease due to glomerulonephritis, patients receiving renal transplantation for the first time, or those from the amikacin group receiving a living-related graft had a significantly lower incidence of UTIs than their counterparts in the control group (p < 0.05). UTIs were most frequently caused by Escherichia coli (28.9%). CONCLUSIONS: Perioperative bladder irrigation with amikacin solution significantly decreases the overall incidence of UTIs in the first 3 months after kidney transplantation.

Ten-year graft survival of deceased-donor kidney transplantation: a single-center experience.

BACKGROUND: Kidney transplantation is the treatment of choice for end-stage renal disease that restores the patients' quality of life and reduces the morbidity and mortality rates induced by renal failure and its complications. However, after transplantation the organ and patient survival rates are important issues of interest in many centers worldwide. SUBJECTS AND METHODS: This is a historical cohort study planned to determine the organ survival rate after kidney transplantation from deceased donor during a period of 10 years (March 1999-March 2009) in Shiraz Transplant Center, Namazi Hospital, Shiraz, Iran. We tried to clarify the probable contributory risk factors implicating in graft loss. Kaplan-Meier method was used to determine the survival rate. Log-rank test was used to compare survival curves, and Cox regression model to define the hazard ratio and for modeling of factors implicating in survival rate. RESULTS: Mean follow-up period was 37.54 +/- 28.6 months. Allograft survival rates at 1, 3, 5, and 9 years after kidney transplantation from deceased donor (calculated by Kaplan-Meier method) was found to be 93.7, 89.1, 82.1, and 80.1%, respectively. Duration of dialysis before operation and creatinine level at discharge were showed to be the most important factors influencing survival rate of renal allograft. CONCLUSION: Overall long-term graft survival in our cohort is satisfactory and comparable with reports from large centers in the world. Duration of dialysis before operation and creatinine level at discharge are the only independent factors that could correlate with long-term graft survival in our cohort.

Vaccination status in pediatric liver transplant candidates.

Infection is a recognized and potentially serious complication in children following solid organ transplantation. This problem is particularly important for young children undergoing any organ transplantation who often have not completed standard childhood immunizations at the time of transplantation and who are therefore at risk for vaccine-preventable infections. To evaluate the vaccination status in liver transplant candidates, vaccination charts of 100 patients who were referred to Organ Transplant Center of Nemazee Hospital were reviewed and the vaccination status considered appropriate according to the recommendation of NIP and the patients' age. Fifty-eight percent of patients were completely vaccinated for HBV, 85% for OPV, 97% for BCG, 63% for DTP, and 58% of the patients were completely vaccinated for MMR. We concluded that the vaccination charts should be periodically reviewed and updated to prevent the vaccine-preventable disease in liver transplant candidates not only before but also after transplant. Every effort should be made to assure that candidates are immunized early in the course of their disease. Also it may be indicated to recommend a special guideline for immunization of liver transplant candidates and add other vaccines such as Haemophilus influenzae and Streptococcus pneumoniae vaccine to their vaccination program.

Effects of surgical technique on postoperative renal function after orthotopic liver transplant.

OBJECTIVES: The classic technique for orthotopic liver transplant consists of the total excision of the retrohepatic inferior vena cava during native hepatectomy. Controversy about the effects of the classic technique on postoperative renal function continues. The aim of this study was to evaluate the effects of the chosen hepatectomy technique on postoperative renal function. MATERIALS AND METHODS: Of 253 patients who received an orthotopic liver transplant between June 2006 and July 2008 in the Shiraz transplant unit, only 15 underwent operation with the classic technique. Patient demographics and factors including cold ischemic time, warm ischemic time, operative time, transfusions, blood loss, and early postoperative renal function were assessed retrospectively. The criteria for acute renal failure were a serum creatinine level of > 133 micromol/L (1.5 mg/dL), an increase in the baseline serum creatinine level by 50%, or oliguria requiring renal replacement therapy. RESULTS: All patients received a liver from a deceased donor, and none required venovenous bypass during the operation. The minimum mean arterial blood pressure value of the patients during clamping was 65 -/+ 19 mm Hg. The mean preoperative plasma creatinine level was 87.51 -/+ 39.78 micromol (0.99 -/+ 0.45 mg/dL). During the first week after transplant, 7 patients (46.6%) experienced acute renal failure, and 3 of those 7 required renal replacement therapy. By the sixth postsurgical month, 4 of those 7 patients had died (1 from adult respiratory distress syndrome, 2 from sepsis, and 1 from recurrent cholangiocarcinoma). In all other patients, the plasma creatinine level had returned to the normal range by the third postsurgical week 3 or during short-term follow-up. CONCLUSIONS: Use of the classic technique for orthotopic liver transplant may increase the rate of postoperative renal failure, but that complication usually resolves during short-term follow-up.

Outcome of bowel perforation after pediatric liver transplantation.

Bowel perforation is one of the causes of mortality after pediatric liver transplantation. The aim of this study was to evaluate the incidence, risk factors, clinical presentations, and outcomes of bowel perforation in pediatric liver recipients. This is a retrospective analysis of all pediatric patients who underwent liver transplantation at a single liver transplant center in Iran between 1999 and 2006. During this period 72 liver transplantations were performed in children <18 yr. Twenty-two children underwent 33 re-explorations after liver transplantation. Five bowel perforations occurred in four children (incidence, 6.9%). One patient required two re-explorations. The median time between liver transplantation and the diagnosis of the bowel perforation was seven days. All patients had abdominal distention before re-exploration. The sites of perforation were jejunum (n = 3) and ileum (n = 2), and simple repair was performed in all cases. Three children had a history of prior Kasai operation. One of them received high dose of methylprednisolone before bowel perforation. Two children expired after bowel perforation (mortality rate, 50%). Bowel perforation is relatively frequent after pediatric liver transplantation. Among risk factors, prior Kasai operation may have a role. We observed that abdominal distention is a sign of bowel perforation and a high index of suspicion is required for rapidly diagnosis of this complication. The outcome of bowel perforation is poor and its mortality is high. Further studies are needed to establish real risk factors for this complication.

Effect of D-penicillamine on liver fibrosis and inflammation in Wilson disease.

BACKGROUND: Wilson disease is a disorder of copper metabolism characterized by copper overload. A mutation in the ATP7B gene causes dysfunction of ATP7B protein and a reduction in copper excretion into the bile in hepatocytes. Excess copper accumulation leads to liver injury. D-penicillamine primarily can inhibit fibrogenesis and prevent the appearance of scar lesions in the liver. We studied this phenomenon in our patients. MATERIALS AND METHODS: Pathology slides from the explanted livers of 26 patients diagnosed as having Wilson disease with hepatoneurologic manifestations between 2000 and 2008 who had undergone a liver transplant were investigated retrospectively. Patients were divided into 2 groups according to their history of D-penicillamine use before transplant. The degree of fibrosis and inflammation were classified as mild (1), moderate (2), and severe (3), and were reviewed by an impartial hepatopathologist. RESULTS: Of 26 patients (20 male, 6 female) who had Wilson disease with a mean age of 17.6 -/+ 8.6 years, 69% (18/26) had a history of D-penicillamine use before liver transplant from 6 months to 9 years (mean, 3.4 -/+ 2.7 years). In the D-penicillamine group, 14 patients (77%) had grade 1 fibrosis. Grade 2 and 3 fibrosis was seen in 5.6% and 16% of patients, respectively. In the D-penicillamine group, inflammation was grade 3 in 44% (8/18), grade 2 in 44% (8/18), and grade 1 in 11% of the patients (2/18). In the non- D-penicillamine group (8 patients), grades of fibrosis were grade 3 (62%), grade 2 (25%), and grade 1 (12%); 87% of the patients had grade 2 and 3 inflammation. The degree of fibrosis was significantly lower in the D-penicillamine group than it was in the non-D-penicillamine group (P < .05). CONCLUSION: D-penicillamine may reduce the rate of liver fibrogenesis in patients with Wilson disease.

Liver Transplantation Status in Iran: A Multi-center Report on the Main Transplant Indicators and Survival Rates.

BACKGROUND: Iran's experience with liver transplantation (LT) began more than two decades ago. The purpose of this article is to present the status of LT in Iran, review specific characteristics of the programs, their outcomes, and their growth to become one of the largest LT programs in the world. METHODS: A questionnaire, asking for data on the number of transplants performed and specifics of the recipients and type of donors with focus on indications and outcomes was sent to LT programs. RESULTS: During a period of 23 years, 4,485 LTs were performed at 6 centers in the country. Of these, 4106 were from deceased donors and 379 were from living donors. There were 3553 adults and 932 pediatric recipients. Hepatitis B and biliary atresia were the most common etiologies in adult and pediatric patients, respectively. Overall survival rates at 1, 5, and 10 years were 85%, 77%, and 71% for adults and 76%, 67% and 56% for pediatric patients, respectively. CONCLUSION: Approval of the brain death law in Iran and coordinated efforts by the transplant centers to build comprehensive LT programs has resulted in the ability to procure more than 700 deceased donors per year with acceptable long-term survival.

Transplantation of a horseshoe kidney.

Experience with horseshoe kidney transplantation is limited. Horseshoe kidney may be underutilized for transplantation because of the greater incidence of vascular and other associated urological anomalies. Nowadays, owing to a greater number of patients waiting for a kidney donation and to a shortage of organs donated, more suitable organ acceptance criteria have been formulated. The aim of this paper is to present the first Iranian experience with horseshoe kidney transplantation.

Analysis of patients listed for liver transplantation in Shiraz, Iran.

AIM: To analyze records of patients listed for liver transplantation (LT) at our hospital, the first and the largest LT center in Iran. METHODS: We analyzed medical records of patients aged 14 years or older, who were listed for LT for chronic liver disease between 1994 and 2004. Outcome was determined from records or follow-up data. RESULTS: Among the 480 patients (mean age 39 [SD 13] years; 327 [68.1%] men) listed for LT, common causes of cirrhosis were cryptogenic (143; 29.9%) and hepatitis B (127; 26.5%). Child-Turcott-Pugh (CTP) class distribution of these patients was: A - 37 (7.7%), B - 258 (53.7%) and C - 185 (38.6%). Mean (SD) follow-up duration was 11.4 (11.8) months (range 1-108). One hundred and four (21.7%) patients received LT and 173 (36%) died while awaiting LT. CTP class influenced 1-year (90%, 73% and 55% in class A, B and C, respectively) and 2-year (84%, 48% and 25%, respectively) survival rates. MELD score also influenced survival. Survival was better in patients who underwent LT than in those who continued on the waiting list (p< 0.01). CONCLUSION: Only about one-fifth of patients listed for LT in Iran received LT and a large proportion died without LT.

Adrenal cystic lymphangioma presented with hypertension: a case report.

INTRODUCTION: Adrenal cystic lymphangioma is a rare benign tumor, which is nearly always asymptomatic and incidentally discovered during routine imaging work-ups or investigating other pathologies. CASE REPORT: A 43-year-old female presented hypertension, which during routine work-up of her newly diagnosed hypertension an adrenal mass was discovered and after operation the pathologic diagnosis was lymphangioma of adrenal. CONCLUSIONS: In evaluation of adrenal masses cystic lymphangioma should be considered as a differential diagnosis.

Gastrotracheal Fistula as a Result of Transhiatal Esophagectomy for Esophageal Cancer: An Unusual Complication.

Gastrotracheal fistula following open transhiatal esophagectomy (Orringer's technique) for esophageal cancer is an unusual but lethal complication. Surgical intervention with resection of the fistula tract and primary interrupted suturing of gastric and tracheal orifices using a muscle flap interposition has proved to be a successful method. We report the case of a 73-year-old male with an adenocarcinoma of the distal part of the esophagus, who underwent open transhiatal esophagectomy (Orringer's technique) with gastric tube reconstruction and cervical anastomosis. The patient did not receive induction chemoradiotherapy before the esophagectomy. Two attempts of surgical repair of fistula failed and the patient died. Being aware of warning signs such as dyspnea and respiratory distress accompanied by bilious content in the tracheal tube is helpful in the early detection and treatment of this type of fistula.

A comparative study of the classic and piggyback techniques for orthotopic liver transplantation.

BACKGROUND: The classic technique of hepatectomy with venovenous bypass may cause a longer anhepatic phase and increase the rate of some complications, such as post-operative renal failure and thromboembolic events. But, in some cases, such as tumors and anatomic difficulties, the surgeon is obligated to use the classic technique even though there is some controversy about the safety of this technique without venovenous bypass in liver transplantation. The aim of this study was to compare the results of using the classic technique without venovenous bypass and the piggyback technique for liver transplantation. METHODS: A retrospective case-series study was conducted on 227 consecutive successful liver transplants, including 55 cases in which the classic technique was used and 172 cases in which the piggyback technique was used. The transplants were performed from March 2010 through June 2011 in the Visceral Transplantation Ward at Namazi Hospital in Shiraz, Iran. The piggyback method was the preferred approach for hepatectomy, but the classic technique without venovenous bypass was performed in cirrhotic cases with anatomic difficulties, when there was a tumor, or when the surgeon preferred it. RESULTS: There were no significant differences in post-operative rise in creatinine, decreases in intraoperative blood pressure, transfused packed red blood cells (RBC), or survival rates between the groups. Warm ischemic time (duration that donor liver is out of ice until it's blood reperfusion in the recipient) was approximately seven minutes longer in the classic group (P = 0), but it was less than 52 minutes, which is an acceptable time for this phase. Hospital stays were shorter in the classic group than in the piggyback group (P = 0.024). CONCLUSION: Although the piggyback technique is the preferred technique for hepatectomy in liver transplantation, the classic technique without venovenous bypass can be used safely in cirrhotic livers when necessary or if the physician prefers it.