Efficacy of mTOR Inhibitors and Intravenous Immunoglobulin for Treatment of Polyoma BK Nephropathy in Kidney Transplant Recipients: A Biopsy-Proven Study.

OBJECTIVES: We investigated the efficacy of a predetermined protocol that consisted of immunosuppressive drug reduction/withdrawal and intravenous immunoglobulin administration for the treatment of polyoma BK virus nephropathy. MATERIALS AND METHODS: Patients with biopsy-proven polyoma BK virus nephropathy received a treatment regimen based on discontinuation of both calcineurin inhibitors and antiproliferative agents and switching to mTOR inhibitors accompanied by intravenous immunoglobulin administration. RESULTS: Our study included 508 patients, with polyoma BK viremia detected in 80 patients. The mean age was 45.3 ± 9.5 years (range, 18-71 y), 64% were male, and mean follow-up was 37 ± 21 months (6-94 mo). All 16 patients who developed polyoma BK virus nephropathy and 9 patients who had highgrade polyoma BK viremia without nephropathy received intravenous immunoglobulin treatment. Compared with patients with viremia, patients with polyoma BK virus nephropathy had significantly higher rates of graft loss due to rejection (18.8% vs 1.6%; P = .024) and all-cause graft loss (31.2% vs 6.3%; P = .014). Histopathologically, viral inclusion bodies disappeared and SV40 became negative after treatment in all 13 patients who underwent protocol biopsies. Unfortunately, histopathologically complete recovery without chronic tubular and interstitial tissue damage was achieved in only 4 patients after treatment. In addition, 3 patients lost their grafts due to acute antibody-mediated or mixed-type rejection (18.8%). CONCLUSIONS: In patients with polyoma BK virus nephropathy, clearance of viremia and SV40 should not be the sole outcomes to obtain. Aggressive reductions in maintenance immunosuppression and switching to double-drug therapy combined with high-dose intravenous immunoglobulin leads to high rates of graft loss/rejection and sequalae of chronic histological changes.

Genitourinary Cancers Following Kidney Transplant: Our 20 Years of Experience With Mechanistic Target of Rapamycin Inhibitors.

OBJECTIVES: We investigated patients with genitourinary cancer after kidney transplant and the effects of immunosuppression reduction and switching to mechanistic target of rapamycin inhibitors. MATERIALS AND METHODS: We retrospectively evaluated kidney transplant recipients seen at our center between January 2000 and January 2020. Patients with <1 year of follow-up were excluded. RESULTS: Of 827 patients, genitourinary cancer was detected in 11 (1.3%): prostate cancer in 5 patients (45%), renal cell carcinoma in native kidney in 3 (27%), renal cell carcinoma in allograft kidney in 2 (18%), and transitional cell carcinoma of the bladder in 1 (9%). All patients had surgery. Two patients had bone metastasis due to prostate cancer at diagnosis. Two patients had allograft nephrectomy due to de novo renal cell carcinoma. Mean follow-up and age were 97 ± 45 months (range, 26-189) and 50 ± 10.2 years (19% female). After cancer diagnosis, excluding the 2 patients with allograft nephrectomy, immunosuppression was changed in 8 patients (88.8%) (1 patient received the same treatment before and after cancer diagnosis). Six patients received double-drug and 3 received triple-drug protocols. Of 9 patients, 2 were already using mechanistic target of rapamycin inhibitors before cancer diagnosis and 7 were switched: 4 to double-based and 3 to triple-based regimens. Six were switched from tacrolimus. With new treatments, patients showed no progressive kidney failure or rejection (38 ± 40 mo average follow-up). At last follow-up, mean glomerular filtration rate was 62.8 ± 34 mL/min/1.72 m2, which was similar to rate at cancer diagnosis (58.9 ± 24 mL/ min/1.72 m2; P = .78). During follow-up, no patients developed local recurrence of primary tumor or new metastasis, and none showed adverse effects after switch to mechanistic target of rapamycin inhibitors. Three patients died of malignancy-unrelated reasons (ileus, urinary sepsis, heart failure). CONCLUSIONS: Mechanistic target of rapamycin inhibitor-based drugs can be an important maintenance immunosuppressive treatment option for kidney transplant recipients with genitourinary cancers.

Outcomes of 6 Human Leukocyte Antigen-Mismatched Living Donor Kidney Transplant: A Study With Biopsy Amendment.

OBJECTIVES: In this study, we examined the graft and patient survival outcomes in patients with end-stage kidney disease who received 6 HLA-mismatched incompatible living donor kidney transplant. MATERIALS AND METHODS: Patients who underwent living donor kidney transplant between January 2010 and March 2020 were evaluated retrospectively. Group A included kidney transplant recipients with 6 HLA mismatches, and group B included kidney transplant recipients with 0 to 5 HLA mismatches. Patients with <1 year of follow-up were excluded. All rejection episodes were diagnosed via Tru-Cut biopsy and histopathological evaluation. RESULTS: There were 15 patients in group A and 176 patients in group B. The mean follow-up was 54.1 ± 30 months. The number of patients who underwent pretransplant immune desensitization and received tacrolimus-based triple maintenance immunosuppression therapy was significantly higher in group A. In group A, there were 13 acute rejections seen in 9 patients (81<); in group B, there were 67 acute rejections seen in 51 patients (28.9<; P = .019). No differences were observed between the groups in terms of baseline glomerular filtration rate (60 ± 16 vs 61.6 ± 20 mL/min/1.72 m2; P = .76), final control glomerular filtration rate (60.7 ± 15 vs 58 ± 19 mL/ min/1.72 m2; P = .59), graft loss (0< vs 4<; P = .94), and mortality (6.6< vs 3<; P = .39). CONCLUSIONS: The presence of 6 HLA mismatches was associated with higher rates of biopsy-proven acute rejection. However, 6 HLA-mismatched incompatible living donor kidney transplant can be safely performed in centers where posttransplant followup is supported by indication and protocol biopsies and where there is a pathological infrastructure with extensive knowledge and experience.

Subgaleal and epidural metastases of the undifferentiated embryonal sarcoma of the liver.

Undifferentiated embryonal sarcoma of the liver (UESL) is very rare and has a very poor prognosis. UESL metastases have been reported in 5%-13% of the children with UESL and most metastases reported in the literature are present at diagnosis. Metastases reported in the literature belong to the lungs, pleura, and peritoneum. Radiological diagnosis of the UESL remains a poorly understood problem due to its rarity. Most of the reports published in the literature are also based on a relatively small number of patients. Approximately 200 cases have been reported regarding imaging features of this tumor. We reported a girl with UESL, who applied to the emergency department with abdominal pain. The lesion was solid and had cystic areas on ultrasound and there were peripherally enhanced serpenginous vessels in the lesion on Computed Tomography and MRI. Immunohistochemical diagnosis of the lesion was UESL. 26 months after surgery and adjuvant chemotherapy extradural and subcutaneus metastases were detected. These metastasis sites were first described for UESL.

Comparison of Urinary Tract Dilatation and Society of Fetal Urology systems in the detection of vesicourethral reflux and renal scar.

PURPOSE: The presence and degree of hydronephrosis is very important in the management of many diseases of the urinary tract. In this study, we aim to compare the sensitivity and specificity of 2 classification systems that are used for hydro-nephrosis grading in ultrasound, for reflux and scar detection. The classification systems were the Society of Fetal Urology (SFU) and Urinary Tract Dilatation (UTD). MATERIAL AND METHODS: Ultrasounds and dimercaptosuccinic acid scintigraphies (DMSA) of all patients who underwent voiding cystourethrogram (VCUG) due to urinary tract infection were examined retrospectively. DMSA was accepted for scar detection and VCUG for reflux detection as reference methods. SFU classification was used for hydronephrosis in ultrasound reports, and UTD classification was made over the reports. Sensitivity, specificity, and positive and negative predictive values of UTD and SFU classification systems for reflux and scar detection were calculated, and these 2 systems were compared. RESULTS: 103 (39%) of the patients were male and 162 (61%) were female. Pathologies were detected in 192 (35%) of 530 kidneys in ultrasound. In 110 (42%) of the children, reflux was detected in VCUG. Scars in DMSA were detected in only 16% (44) of 266 kidneys. Sensitivity, positive and negative predictive values of the UTD classification system were statistically significantly higher than the SFU system for scar and reflux detection (p < 0.01). CONCLUSIONS: If we use the UTD system in ultrasounds of patients with urinary tract infections, children reported as UTD 0 may not need VCUG, which reduces radiation exposure to children and the cost of the diagnostic interventions.

Pediatric renal transplantation; 10 years experience.

Objectives: Although renal transplantation (RT) is the first treatment option for children with end-stage renal failure, the number of transplanted chil- dren remains low compared to adults. Experience of the individual pediatric transplant center is very important in the prognosis of pediatric transplant recipients. In this study, our pediatric RT experience was presented. Material and Methods: We retrospectively analyzed the data of 27 patients who had RT in our clinic between April 2009 and April 2019. Results: Fifteen of the patients were males, and mean age of all patients was 12.36 ± 4.18 years (range 4-17 years). The most frequent etiology for end- stage renal disease (ESRD) was vesicourethral reflux. Eighteen (66.7%) of the transplanted kidneys came from cadaveric donors and 9 (33.3%) from live donors. One patient had preemptive RT and one patient had a re-RT. Twenty-two patients were on peritoneal dialysis program and four patients were on hemodialysis program. Mean dialysis time before transplantation was 29 (3-104) months. Bleeding was the most common surgical complication. Delayed graft function developed in four patients, and all of their grafts were from cadaveric donors. Rejection developed in 12 of our patients, graft loss was observed in only four of them. Considering all patients, graft survival rates were 100% in the 1st and 3rd years, and 92% in the 5th year. Conclusion: Pediatric RT program is difficult to establish, maintain and develop. Complications after transplantation are not uncommon; therefore, early detection and appropriate management are needed. Strategies are still needed to increase post-transplant success.

Comprehensive Analysis of Long-term Splenic Volume Changes in Pediatric Liver Transplant Patients: Does It Correlate With Adverse Graft Outcomes?

OBJECTIVES: Splenomegaly and hypersplenism caused by liver failure increase the mortality and morbidity of patients even after liver transplantation if they do not regress. We evaluated the relation of splenic volume change and transplanted liver function. MATERIAL AND METHODS: A total of 59 of 207 pediatric patients who had liver transplantation between 2013 and 2018 in our institute were evaluated. The relation of spleen volume changes (splenic volume to standard splenic volume ratio [SV/SSV]) were measured at 0, 1, 6, 12, 24, and 36 months of follow-up by constructing electronic three-dimensional structure of the spleen at dynamic computed tomography (CT), and the course of liver functions were evaluated. RESULTS: The SV/SSV ratio decreases in the first postoperative 6 months. After 6 months, SV increases and SV/SSV increases gradually. In a normal functioning graft, SV/SSV significantly decreased in all time points (P < .001). In patients with adverse events, SV/SSV started to increase after 6 months. In patients with fulminant hepatic failure, SV/SSV started to increase after postoperative 6 months. Adverse events in patients with fulminant hepatic failure were more than the patients with chronic liver disease (58% vs 28%). There was an inverse correlation between SV/SSV and thrombocyte levels (P < .001). CONCLUSIONS: SV/SSV seems to be correlated to the adverse events (ie, rejection). Together with thrombocyte levels, it can be used as a noninvasive test for follow-up of transplant patients in terms of adverse events in graft function.

Living Donor Versus Deceased Donor Liver Transplantation for HCC.

INTRODUCTION: Liver transplantation is the definitive treatment modality of the patients having an end-stage liver disease with hepatocellular carcinoma. DISCUSSION: The number of living donor liver transplantations has been increased because of the deceased donor organ shortage, especially in Asian countries. CONCLUSION: Reports of different clinics about the postoperative course and tumor recurrence rates comparing living donor versus deceased donor liver transplantations, besides patient selection criteria, are reviewed along with our clinic's experiences.

Is peritoneal dialysis prior to kidney transplantation a risk factor for ureteral stenosis after adult to adult live kidney transplantation.

OBJECTIVES: Major urinary complications such as urinary leaks, stenosis or urinary tract infections after kidney transplantation can lead to graft or patient loss. The effect of peritoneal dialysis on post-kidney transplantation complications have been discussed but its effect on ureteral stenosis is unknown. In this study, it was aimed to analyze factors effecting major ureteral complications after living donor kidney transplantation and impact of peritoneal dialysis and double J-stents (JJ stents). MATERIAL AND METHODS: This study included 116 adult to adult living donor kidney transplant patients. Factors effecting major urologic complications after living donor kidney transplantation were analyzed. The donors were primary relatives of the recipients. RESULTS: Major urologic complications after living donor kidney transplantation was 8/116 (6.9%). Urinary leak was present in 2 (1.7%) patients. Ureteral stenosis was encountered in 6 (5.2%) patients. Double J stents were used in 84 (72.4%) of the cases. The effect of JJ ureteral stent was not statistically significant for urinary leak, ureteral stenosis (p= 0.074, p= 0.470, respectively). A total of 29 (25%) patients had peritoneal dialysis before kidney transplantation. Preoperative peritoneal dialyses and bacteriuria after kidney transplantation were independent risk factors for ureteral stenosis in multivariate analysis (p= 0.013, and p= 0.010 respectively). CONCLUSION: In the guidance of the results of the present study, peritoneal dialysis prior to kidney transplantation and bacteriuria are independent risk factors for ureteral stenosis after living donor kidney transplantation. JJ stents have no effect on urologic complications after living donor kidney transplantation.

Reconstruction of Anomalous Portal Venous Branching in Right Lobe Living Donor Liver Transplantation: Malatya Approach.

Reconstruction of anomalous portal vein branching (APVB) during right lobe living donor liver transplantation (LDLT) can be challenging. The goal of this article is to describe our surgical technique, named the Malatya Approach, in case of APVB during right lobe LDLT. The technique unifies the APVB and obtains a funnel-shaped common extension with a circumferential fence by a saphenous vein conduit. In total, 126 (10.6%) of 1192 right lobe grafts had APVB that were divided into 2 groups according to the adopted surgical techniques: the Malatya Approach group (n = 91) and the previously defined other techniques group (n = 35). Both groups were compared regarding portal vein thrombosis (PVT), postoperative 90-day mortality and survival. PVT developed in 3 patients (3.3%) in the Malatya Approach group and developed in 10 (28.6%) patients for the other group (P < 0.001). There were 8 (8.8%) 90-day mortalities in the Malatya Approach group (1 PVT related) and 15 patients (9 PVT related) died in the other techniques group (P < 0.001). Mean follow-up time for both groups was similar (999.1 days for the Malatya Approach group versus 1024.7 days for the other group; P = 0.47), but longterm survival in the Malatya Approach group was better than in the other group (84.6% versus 40%; P < 0.001). Multivariate analysis revealed that the Malatya Approach group showed less PVT development and longer survival (P < 0.001). This technique is promising to avoid PVT and mortalities in cases of APVB during right lobe LDLT. Liver Transplantation 23 751-761 2017 AASLD.

Pediatric small bowel transplantation: A single-center experience from Turkey.

BACKGROUND/AIMS: Small bowel transplantation (SBTx) is a treatment option for patients with serious parenteral nutrition-related problems in intestinal failure. Izmir Tepecik Training Research Hospital Organ Transplantation Center is still the only pediatric intestinal transplant center in Turkey. MATERIAL AND METHODS: This study was approved by the local ethics committee. Patients' data were analyzed from the medical charts and the hospital digital database. Seven isolated SBTxs were performed in six children between 2010 and 2016. RESULTS: One jejunal segment and six partial jejuno-ileal segments were used for seven transplants. All grafts were retrieved from deceased donors (one child and six adult donors). The six recipients had a mean age of 8.8±6.9 years (9 months to 17 years; M: 4, F: 2). The mean follow-up period of patients was 727±848 (34 to 1950) days. Acute cellular rejection (ACR) rates were 57% (n: 4) in the first 2 months. Graft loss due to severe ACR was seen in one patient. Central line-associated fungal (n: 3, 42%) and bacterial infections (n: 3, 42%) were seen in the first 2 months. Two Epstein-Barr virus (EBV) infections were recorded between 3 and 8 months in two patients. Our 1-year patient and graft survival rates were 71% and 71%, respectively. CONCLUSION: SBTx has become a treatment modality for patients with intestinal failures. Management of ACR and infections are still challenging problems in SBTx. Appropriate-sized cadaveric donors are very limited in Turkey for pediatric intestinal transplantation candidates. Although the number of SBTxs performed was small, this study shows promising results.

Immune profile of asplenic patients following single or double vaccine administration: A longitudinal cross-sectional study.

OBJECTIVE: Splenectomy poses a lifelong threat for the development of uncontrolled sepsis despite vaccination. As it is impractical to measure the levels of each antibody against 23 most frequent bacterial serotypes, different surrogate markers of immune response should be identified. MATERIAL AND METHODS: Forty-eight patients with benign disorders were vaccinated with Pneumo-23 and Act-HIB before or at the day of surgery. The immunological response and opsonization capacity of the patients after splenectomy was analyzed through the quantitative measurement of IgG, IgM, C3, and C4 titers; flow-cytometric analysis of (CD3+) T-lymphocytes and (CD19+) B-lymphocytes; and isolation of CD27+ B cells by immunomagnetic positive selection. Blood samples were drawn at the sixth month and 5 and 7 years after surgery. RESULTS: The mean follow-up period was 98.4 months. All the patients in this series had normal IgG, C3, C4 levels and a normal distribution of CD19+ B-cells and CD8+ T-cells in three follow-up periods. Moreover, C3 levels markedly improved to 133.5±37.3 mg/dL at 5 years and remained stable thereafter. CD19+ B-lymphocyte values have progressively improved to the normal range in 98% patients at 7 years. Further, low levels of CD27+ B-cell population (memory cells) was observed in only 12.5% patients at the last follow-up. Adequate seroconversion of IgG, IgM with normal C3, C4, and CD19+ B-cell levels were accomplished in almost all patients. Early postoperative death and late overwhelming infections did not occur. CONCLUSION: Our results are indicative of the resumption of the immune function following Pneumo-23 and Act-HIB administrations, instigated by the probable activation of B cells and adequate production of C3, C4, IgG, and IgM antibodies in remote lymphoid tissues.

The effect of cold ischemia time on delayed graft function and acute rejection in kidney transplantation.

The objective of this study is to evaluate the impact of cold ischemia time (CIT) on delayed graft function (DGF) and acute rejection (AR) among deceased donor kidney transplant recipients. The medical records of 111 patients who underwent kidney transplantation from deceased donors between November 1994 and July 2009 were retrospectively analyzed. DGF was observed in 54% of the patients and the prevalence of AR in the first year after transplantation was 9.9%. The incidence of DGF was higher among patients with longer CIT. There was no correlation between CIT and AR episodes. Higher body weight of recipients and donors, history of prior blood transfusion and advanced donor age were related with DGF. Patients with DGF had higher serum creatinine levels at the first, third and fifth years. There was a negative correlation between recipient body weight and creatinine clearance at the first year. CIT has an important role in the development of DGF as a modifiable risk factor. Moreover, donors with advanced age and higher body weight as well as recipients with higher body weight and history of blood transfusions are at risk for the development of DGF. Prevention of DGF may help to improve graft function at the first, third and fifth years and shorten the hospital stay.

Mesenchymal stem cell therapy in patients with small bowel transplantation: single center experience.

AIM: To study the effects of mesenchymal stem cell (MSC) therapy on the prevention of acute rejection and graft vs host disease following small bowel transplantation. METHODS: In our transplantation center, 6 isolated intestinal transplants have been performed with MSC therapy since 2009. The primary reasons for transplants were short gut syndrome caused by surgical intestine resection for superior mesenteric artery thrombosis (n = 4), Crohn's disease (n = 1) and intestinal aganglionosis (n = 1). Two of the patients were children. At the time of reperfusion, the first dose of MSCs cultured from the patient's bone marrow was passed into the transplanted intestinal artery at a dose of 1000000 cells/kg. The second and third doses of MSCs were given directly into the mesenteric artery through the arterial anastomosis using an angiography catheter on day 15 and 30 post-transplant. RESULTS: The median follow-up for these patients was 10.6 mo (min: 2 mo-max: 30 mo). Three of the patients developed severe acute rejection. One of these patients did not respond to bolus steroid therapy. Although the other two patients did respond to anti-rejection treatment, they developed severe fungal and bacterial infections. All of these patients died in the 2(nd) and 3(rd) months post-transplant due to sepsis. The remaining patients who did not have acute rejection had good quality of life with no complications observed during the follow-up period. In addition, their intestinal grafts were functioning properly in the 13(th), 25(th) and 30(th) month post-transplant. The patients who survived did not encounter any problems related to MSC transplantation. CONCLUSION: Although this is a small case series and not a randomized study, it is our opinion that small bowel transplantation is an effective treatment for intestinal failure, and MSC therapy may help to prevent acute rejection and graft vs host disease following intestinal transplantation.

S-shaped wide excision with primary closure for extensive chronic pilonidal sinus disease.

Background. The management of complex pilonidal sinus disease (PSD) with multiple pits on and beside the natal cleft is variable, contentious, and problematic. Wide excision of the sinus and reconstruction of the defect using different flap techniques have become more popular in recent years. Case Report. We report a case with a complex chronic PSD to which we applied primary closure after S-shaped wide excision. The patient's postoperative course was uneventful, and at the end of one-year followup he is now disease-free and comes for routine checkups. Conclusion. The simplicity of the technique and the promising results support the applicability of the S-shaped wide excision in chronic bilaterally extended large PSDs. Further studies entailing large patient populations are needed to reach a definite conclusion.

Longitudinal surveillance of mid- and distal rectum cancer in a subset of patients with specific histology.

OBJECTIVE: A prospective study in 82 consecutive patients with mid- and distal rectal adenocarcinomas having specific histology and tumor stage was conducted to asses impact of curative surgery. METHODS: Patients with moderately differentiated adenocarcinoma (MDAC) with or without mucinous differentiation underwent curative resection. Forty patients were in Stage B1-B2 and 42 patients were in Stage C1-C2. Surgery options were: (1) Abdominoperineal resection (APR) for tumors located within 6cm of the anal verge and (2) Tumor specific mesorectal excision (TSME) and low anterior anastomosis (LAA) for those located between 6 to 12cm from the anal verge. The primary endpoints were overall (OS) and disease-free survival (DFS). RESULTS: Patients in Stage B1-B2 had a local failure rate of 15% compared with 31% of patients in stage C1-C2 (p=0.18). Satellite tumor nodule formation (STN) was observed in one patient in B group and in 13/42 (31%) of Stage C tumors. LR did not vary with mucinous differentiation. Only lymph node involvement (N1-3) (p=0.028) had an impact on locoregional recurrence and both lymph node involvement and STN formation influenced disease-free survival (p=0.008). CONCLUSION: Preoperative precise detection of Stage C rectal adenocarcinomas is of utmost importance to facilitate the implementation of therapies for downstaging and for better local and distant control following surgery.