Aydincan Akdur

Biliary Complications After Pediatric Liver Transplantation

OBJECTIVES After liver transplantation, biliary complications are more prevalent in pediatric patients, with reported rates varying between 15% and 30%. METHODS We retrospectively analyzed biliary complications observed in 84 pediatric liver transplantation patients between July 2006 and September 2012. Biliary reconstruction was accomplished via a duct-to-duct anastomosis in 5 (83.3%) of the 6 patients receiving whole liver grafts and in 44 (56.4%) of the 78 patients who received a segmental live donor graft. For the remaining 34 patients with living donor and 1 patient with whole liver graft, Roux-en-Y hepaticojejunostomy was the preferred method. RESULTS Post-transplantation biliary complications were encountered in 26 patients (30.1%). The biliary complication rate was 38% in 49 duct-to-duct anastomosis, whereas it was 20% in the hepaticojejunostomy group consisting of 35 recipients. Thirteen of the 18 biliary leaks were from duct-to-duct anastomoses and the remaining 5 were from the hepaticojejunostomies and 6 of the 8 biliary strictures were observed in recipients with duct-to-duct anastomosis. In 19 of the 26 patients, the biliary complications were successfully treated with interventional radiologic procedures and 1 was treated with stent placement during endoscopic retrograde cholangiopancreatography. CONCLUSIONS Percutaneous interventional procedures are valuable, effective, and life-saving therapeutic alternatives for the treatment of bile leaks and strictures after pediatric liver transplantations.

Early Proteinuria After Renal Transplantation and Allograft Outcomes

BACKGROUND Proteinuria is among the major and nonspecific sign of the renal disease. It is well known that late-onset proteinuria after renal transplantation has been associated with poor allograft outcomes and with mortality. Knowledge about the impact of early proteinuria on the various outcomes is limited. We have evaluated the utility of measuring early proteinuria in the management of pediatric renal transplant recipients. METHODS We analyzed the effect of proteinuria at 3 months of posttransplantation on allograft rejection, graft loss, and estimated glomerular filtration rate (GFR) at 3 years. Proteinuria was assessed using 24-hour urine protein excretion. Renal biopsy was performed when elevated creatinine levels were elevated during routine follow-up and an acute rejection episode was proven with biopsy. RESULTS Sixty-seven pediatric renal transplant recipients were included to the study. Mean follow-up time after transplantation was 48.8 ± 12.1 months. Thirty-nine recipients (58%) have proteinuria >500 mg/d. The relationship could not be shown between proteinuria at posttransplant month 3 and other outcomes parameters, such as graft loss and lower estimated GFR. A significant positive correlation between acute rejection and the proteinuria at posttransplant month 3 was shown. CONCLUSION We demonstrated that early proteinuria is a common finding in children after transplantation. Posttransplant early proteinuria cannot be used as a long-term prognostic marker of poor renal outcome. However, early proteinuria is associated with an high risk of acute rejection episodes. This would permit an opportunity for early intervention.

Results of surgical treatment of anterior abdominal wall desmoid tumours : 13 cases reviewed with literature.

Abstract Background : We retrospectively evaluated the results of surgical treatment for anterior abdominal wall desmoid tumours. Methods : Records for 13 patients operated on for desmoid tumours from 1997–2013 were searched for age, gender, abdominal/pelvic surgical history, pregnancy, Gardner’s syndrome, pre-operative radiological examinations, tumour size, multifocality, surgical procedure, tumour presence at surgical margins, recurrence, morbidity, and mortality. Local recurrence-free survival probabilities were estimated by the Kaplan-Meier method and stratified by various clinicopathologi-cal variables. Results : There were 11 female (84,6%) and 2 male (15,4%) patients with a median age of 36 years. Seven (53,8%) patients had previous abdominal/pelvic surgery, five (38,5%) had a history of pregnancy, and one (7,6%) had Gardner’s Syndrome. Two (15,3%) patients had multifocality on their pre-operative radiological examinations. Mean tumour diameter was 4,6 cm (SD 3,2 cm; range 2–12 cm). After the excision of the masses in five (38,5%) patients, synthetic materials were used to close the abdominal wall defects. Two (15,3%) patients with positive surgical margins after surgery were re-operated. Three (23%) patients required a second surgical intervention after the mass excisions were performed. Mean follow-up time was 56,7 months. Recurrence was observed in three patients during follow-up. Increased tumour size, history of previous abdominal/pelvic surgery, and the presence of multifocality had a negative effect on local recurrence-free survival. There was no mortality during follow-up. Conclusions : Desmoid tumours are characterized by high recurrence, even after proper surgical excisions. Preoperative differential diagnoses of these tumours should be done and a post-operative follow-up protocol should be followed.

Value of early diethylentriamine penta-acetic acid renograms in predicting late allograft outcomes.

BACKGROUND Tc-99m-diethylentriamine penta-acetic acid (DTPA) renal scintigraphy is useful, noninvasive diagnostic tool for the management and follow-up of the transplanted kidney. There have not been any studies of the predictive value of DTPA renal scintigraphy for short- and long-term allograft functions. Our aim was to reveal the significance of different perfusion-uptake patterns observed on Tc-99m-DTPA renal scintigraphy for long-term graft outcomes. METHODS We retrospectively analyzed 59 renal transplanted children (30 male and 29 female). All patients were underwent DTPA on posttransplant day 7. Perfusion- and function-related parameters of DTPA (the ratio of peak perfusion counts to plateau counts [P:PL], the ratio of counts at peak perfusion to counts at peak uptake [P:U], and glomerular filtration rate [GFR] calculated using commercially available software) were studied. The mean P:PL and P:U calculated using the half-moon-shaped background region of interest. A renal time activity curve was generated for evaluate perfusion- and function-related parameters. The patterns were classified and the value of these early DTPA parameters in predicting long-term graft function was analyzed. RESULTS The mean age of patients was 16.69 ± 4.77 years. The mean posttransplant follow-up time was 3.5 ± 0.4 years. Thirty-nine patients received living-related donor allografts and the remaining 20 were from deceased donors. Thirteen children suffered ≥ 1 acute rejection episode. Eight patients lost their grafts during follow-up. Mean GFR value at year 3 was 80.61 ± 39.03 mL/1.73 m(2) BSA/min. There was a significant difference for mean creatinine values at year 3 between recipients with normal perfusion and function and normal P:PL with decreased P:U patterns in early DTPA (P < .05). The normal P:PL with decreased P:U pattern is associated with lowest GFR value at posttransplant year 3. There was also a significant difference for mean GFR values at year 3 between recipients with normal perfusion and function and acute tubular necrosis (P < .05). Acute rejection episodes and graft loss were mostly seen in recipient with a decreased P:PL with or without decreased P:U pattern in early DTPA. The decreased P:PL with or without decreased P:U pattern may be associated with high risk of acute rejection episodes and graft loss. CONCLUSION Posttransplant early perfusion uptake patterns observed on Tc-99m-DTPA renal scintigraphy can be used as a long-term prognostic marker of poor renal outcomes. This would permit an opportunity for early intervention.

Surgical Treatment for Ureteral Obstruction After Kidney Transplantation

Introduction Ureteral obstruction occurs in 2% to 10% of renal transplant patients postoperatively, usually presenting within the first few weeks or the first year. Ureteric ischemia is the most common cause, accounting for around 90% of occurrences. The first option for treatment is interventional radiological methods. Percutaneous therapy of ureteral strictures consists of balloon dilatation with or without temporary stenting. If all of these methods are unsuccessful, surgical treatment should be applied. We evaluate the outcomes of 5 patients who treated with surgical teqniques for ureteral obstruction. Materials and Methods Since November 1975, we performed 2646 RT procedures at two different centers by the same transplantation team. At our institution, we perform ureteral anastomoses by means of a corner saving technique. We performed 7 surgical procedures for ureteral obstructions. All patients with ureteral occlusion had recurrent urinary tract infection before surgical treatment and interventional radiological procedures were performed prior to surgery. Results Four of the patients were living donor kidney transplantation and 3 of them were deceased donor transplantation. Four of them were female. For 4 patients, the old ureteroneocystostomy was terminated and new ureteroneocystostomy was performed. In 1 patient, we performed native nephrectomy and end-to-side anastomosis between the native ureter and graft’s renal pelvis. In 2 patients, we performed ureteroureterostomy and side-to-side anastomosis between the native and graft ureters. During the surgical procedure, double J stent was placed in to the anastomosis and removed in the first month. After reconstruction procedure urinary tract infection did not occur. During the follow up period graft functions are normal. Conclusions Ureteral strictures are rare complications that can lead to graft loss. Prompt diagnosis and remedial treatment are vital to prevent graft loss. The interventional radiological methods are the first choice for treatment, surgical procedures should be performed in patients who do not benefit from these treatments.

Significance of Antibody-Mediated Vascular Rejection (AMVR) on Graft Survival: Correlation with Pure Antibody-Mediated Rejection (AMR)

Introduction Traditionally, endarteritis accepted to associate with cellular rejection. Nevertheless, some of the patients with AMR also had endarteritis at the same time. The risk of graft loss was nine times higher in AMVR than T cell-mediated rejection without endarteritis. However, the importance of the endarteritis on the graft survival in recipients with AMR is controversial. Thus we aimed to understand the prognostic value of the presence of endarteritis in recipients with AMR. Materials and Methods Among 155 recipients 72 (46,5%)had pure AMR (Group 1) while 83 (53,5%) had both AMR and endarteritis (Group 2). Endarteritis graded according to Banff. First indication biopsies of all cases reevaluated and the intensity of interstitial, glomerular and peritubular capillary (PTC) inflammation, neutrophil, macrophage and lymphocyte infiltration graded. HLA-DR expression in the arteries, PTCs, and tubules examined. The loss of DR expression on PTCs accepted as the destruction of PTCs. Follow-up biopsies analyzed for the development of interstitial fibrosis (IF), transplant glomerulopathy (TG) and transplant arteriopathy (TA). Results The extensity of the PTC and arterial C4d expression and the degree of PTC destruction found higher in Group 2 compared to Group 1 (P<.001).The degree of the interstitial eosinophil, plasma, and macrophage infiltration found higher in Group 2 patients than Group 1 (p<.001). Also, the intensity of inflammatory cells and neutrophils in both glomeruli and PTCs found higher in Group 2 compared to Group 1 (p<.001). Compared to Group 1 patients, Group 2 patients showed a higher incidence of IF, TG and TA in follow-up biopsies (p<.01).The development of IF and TG increases with the increasing degree of glomerulitis, PTC-itis, C4d expression and PTC destruction (p<.01). Also, the time of the development of IF and TG decreased with increasing intensity of PTC and interstitial infiltration, glomerulitis, PTC destruction and C4d expression (p<.01). The presence of the eosinophil and macrophage infiltration on the wall of arteries of recipients with AMVR rises the risk of the development of TG and TA (p<.01). Also, patients who had arterial C4d staining had a higher risk of TG, TA and graft loss (p<.001). The response to rejection therapy was lower in Group 2 recipients compared to Group 1 patients (p<.001). Overall the 3- and 5-year graft survival was 98%, and 85% respectively for Group 1 patients while it was 57%, and 27% respectively for Group 2 (p<.001). Conclusion Our results have underlined the importance of the presence of endarteritis in AMR. We showed that the course of AMVR are noticeably different from pure AMR, with AMVR having the worst outcome through leading the early development of IF, TG, and TA via augmenting inflammatory and fibrotic pathways. Thus the development of new treatment strategies for AMVR could salvage many kidney allografts.

The Effects of Graft Weight on Allograft Outcomes in Pediatric Patients

Introduction Renal mass plays an important role for a balanced graft function after transplantation. Our aim is to evaluate the relation between transplanted renal mass and long term graft outcomes in pediatric renal transplant recipients. Materials and Methods Forty six children (M/F: 26/20) with kidney transplant from living related donor were enrolled to the study. Demographic data and laboratory findings were noted. The estimated glomerular filtration rate (eGFR) was calculated by Schwartz Formula. Grafts (Gw) and recipients (Rw) were weighed before transplantation. Patients were divided into three groups according to the Gw/Rw ratios (Gw/Rw<3.9 (P25), Gw/Rw=3.9-9.3 (P25-P75), Gw/Rw>9.3 (P75)). Relation between Gw/Rw ration and allograft outcomes was evaluated. Results Mean age at the time of the transplantation was 14.09±4.71 years. Mean age of donors (M/F:20/26) was 37.97±0.94 years. Mean follow-up time after transplantation was 3.87±1.08 years. Mean weight of recipients was 35.04±2.57 kg, mean weight of donors was 77.06±1.72 kg. Mean Gw/Rw ratio was 6.63±3.69. Delayed graft function was not observed. At 3rd years of follow-up, mean creatinine level was 0.89±0.26 mg/dl and mean GFR value was 97.07±16.86 ml/min. A statistically significant negative correlation was demonstrated between Gw/Rw ratio and creatinine levels at 3rd and 6th months and 1st and 3rd years of follow-up (r=-7.00, p<0.01, r=-7.28 p<0.01, r=-4.70 p<0.01, r=-5.86 p<0.05). Patients with Gw/Rw>9.3 had lowest mean creatinine levels during the first 6 months of transplantation when compared with patients with Gw/Rw ratio<3.9; but this difference between creatinine levels could not be demonstrated after 6th month of transplantation. Gw/Rw ratio was not associated with acute rejection episode and HLA mismatch. Gw/Rw ratio was not an independent risk factor for graft survival at 3rd year of follow-up in a multivariate logistic regression analysis. Conclusion We demonstrated a significant relation between renal mass and creatinine levels after transplantation. Pediatric renal transplantation from an adult donor is mostly results with higher Gw/Rw ratio. Higher Gw/Rw ratio can cause hyperfiltration during the first 6 months of transplantation, but it has no effect on long term outcomes.

Clinical Course of Inflammatory Bowel Disease and Primary Sclerosing Cholangitis after Liver Transplantation

Introduction Primary sclerosing cholangitis (PSC) is a rare progressive cholestatic liver disease with presumed autoimmune etiology. It is characterized by inflammation and fibrosis of the intrahepatic and extrahepatic bile ducts. There is a strong association between PSC and inflammatory bowel diseases (IBDs), particularly ulcerative colitis(UC). The history of inflammatory bowel disease (IBD) after liver transplantation (LT) for PSC has been reported as variable. Even though in majority of the cases, IBD symptoms do not change or improve, there also cases of deterioriation reported. Approximately one third of patients with PSC may develop de nova IBD 10 years after LT. Several studies have focused on the course of IBD after LT. These studies found conflicting results. There is no data of our country in this subject. Our aim is to describe the natural history of IBD and PSC after liver transplantion in our patients. Materials and Methods There were six patients transplanted for PSC who survived more than 12 months. Ulcerative colitis was diagnosed in four of the six(67 %) patients before transplantation. Colonoscopy and biopsy were performed before and after transplantation for all patients. Patients were followed for an average 56 (24-96) months. All received tacrolimus and prednisone with or without azathioprine as maintenance immunosuppression. Results A total of 6 PSC patients were included in this study, 3 males and 3 females. The mean age at LT was 33.6 years (range, 18-43 y). Four of 6 patients with PSC had UC before liver transplantation. After LT, 2 patients (50%) had quiescent disease and were receiving no additional medications other than standard immunosuppression. Two patients (50%) had severe flares which could not be controlled by oral and IV prednisone orazathioprine and undergone total colectomy. Multifocal dysplasia was detected in colectomy specimens in 1 of the 2 cases. De novo IBD was diagnosed in 2 patients. PSC recurred after an average of 8 years in 5 of 6 patients. Two of those patients developed de novo UC at the same time. Four of the patients with recurrent PSC had active UC. Conclusions Preexisting ulcerative colitis often has an aggressive course, while de novo ulcerative colitis may develop in patients transplanted for primary sclerosing cholangitis. An increased risk of colorectal cancer is present also after LT in IBD patients with primary sclerosing cholangitis. Regarding the higher clinical complexity of this subgroup of IBD patients, the management of IBD after LT requires close coordination between transplant surgeon, hepatologists and IBD experts.

Our Experience with Paired Kidney Exchange Transplantation

Introduction Paired kidney exchange (PKE) transplantation has gained popularity worldwide as the best alternative for renal recipient candidates who are sensitized to their donors or have ABO incompatible donors. In this study we present our early results of paired kidney exchange transplants. Materials and Methods We started our PKE transplantation programme in July 2015. Various incompatible pairs were matched depending upon the availability of suitable donors and compatible recipients. Matching and donor allocation was done manually. As far as possible, donors were matched for age and glomerular filtration rate. In a meeting before transplantation, all details of the surgery as well as the legal and ethical requirements were given, informed consent was received. Induction was offered to all patients. Antithymocyte globulin induction therapy was administered at the time of transplantation as well as the third day posttransplant; tacrolimus (target level 8-10 ng/mL), mycophenolate mofetil (1g twice a day) and prednisolone were started as immunosuppressive therapy and tacrolimus was maintained with a target level of 6-8 ng/mL 3 months after the operation. All patients were followed up twice weekly for the first 2 weeks, once weekly for the second 2 weeks, once a fortnight for the second and third months. Data were collected from medical records, including demographic data, follow-up serum creatinine, acute rejections, graft, and patient loss and infections. Results Seven pairs were matched from July 2015 to September 2017 and we performed 14 PKE (5 women, 9 men) transplants. Mean recipient age was 49.8±11.5 (range: 23-61) and mean donor age was 50.4± 12.4 (range: 38-64) years. Five of the donors were fathers, one of them was a mother, 3 were husbands and 5 were wives. Mean mismatch ratio was 5±1 (range: 3-6). Reason for exchange was ABO incompatibility for 10 patients and positive crossmatch and presence of donor specific antibodies for 4 patients. All were 2-way donations. Median waiting time for getting suitable donor after registration was 3 months. Two of the recipients were retransplanted and desensitization with plasmapheresis was needed for panel reactive antibody positivity. One patient underwent preemptive kidney transplant. Mean serum creatinine level at one month and at third month after transplant were 1.03±0.37 and 0.97±0.25 mg/dL. There were only 2 early biopsy-not-proven acute rejection episodes treated with pulse steroids and 2 urinary tract infections treated with oral antibiotics. In 1 patient external iliac artery was replaced with ePTFE vascular graft due to complete dissection. All patients are alive with no serious complications. Conclusions ABO incompatibility continues to pose a serious problem for transplantation candidates, especially in kidney and liver transplants. Our small series shows that PKE transplantation is an alternative for patients without a viable living-related donor or deceased compatible donor organ.

Liver Transplantation and Auxiliary Partial Orthotopic Transplantation Outcomes in Wilson’s Disease: Results of a Single Center

Introduction Liver transplantation (LT) is an effective option for Wilsons disease (WD) patients with neurologic symptoms, acute liver failure and with advance decompansated liver disease. In this retrospective study we aimed to review our LT results for WD patients. Materials and Methods Between December 1988 and October 2017 we performed 580 LT procedures at our center (age range, 6 months-64 years). We performed 53 LT in WD (45 living donor LT, 8 deceased donor LT) and after discharge we followed them for 12-350 months. We evaluated the regression of neurologic symptoms and reported survival, graft function of WD patients after LT. Results We performed LT for acute liver failure in 7 WD patients and for end stage liver failure in 41 WD patients. Five patients had LT for neurological WD. One of these neurological WD patients had auxiliary partial orthotopic LT (APOLT) due to neurological WD without hepatic failure (child A). After APOLT he is doing well with normal liver functions and ceruloplasmin levels. All neurologic symptoms were regressed in all of these 5 neurological WD patients. Four of these 53 WD patients had retransplantation (due to 1 primary non-function and 3 chronic rejections) and 3 retransplant patients are doing well with normal liver functions. Thirteen of 53 WD patients died; 6 patients died in early postoperative period, 7 patients died during their follow up due to complications unconnected to WD. The remaining 40 patients have normal liver functions in their follow up (range 12-350 months). Our long term survival is 85%. Conclusion Liver transplantation for WD with end stage liver failure and neurological WD has good outcomes. We may also consider auxiliary partial orthotopic LT for progressive neurological WD patients with no hepatic insufficiency.