In Vitro Evaluation of New Possible Cell Engraftment Enhancers for Cell Transplantation

Orthotopic liver transplantation (OLT) is the best treatment to restore liver function in liver failure. The low availability of organs has focused interest on the use of cell transplantation to restore liver function. However, this technique is limited because cells can not bind to liver parenchyma and die soon after perfusion. Pretransplant treatment with engraftment enhancers (EE) to increase vascular permeability may increase cell attachment. Using an endothelial cell culture to measure the loss of intercellular endothelial adhesion as a screening test, we evaluated the capacity of 15 monoclonal antibodies against adhesion molecules expressed on endothelial cells to act as EE showing that 3 antibodies (anti-CD54, efalizumab, and abciximab) act as EE by producing disruptions in the cell layer.     

The impact of non-HLA antibodies directed against endothelin-1 type A receptors (ETAR) on early renal transplant outcomes

BackgroundNon-HLA antibodies (Abs) targeting vascular receptors are considered to have an influence on renal transplant injury. Anti-endothelin-1 type A receptor (anti-ETAR) antibodies were associated with cellular and antibody-mediated rejection and early onset of vasculopathy in heart transplant patients but their role in renal transplantation remains unclear. The aim of our study was to assess the incidence and importance of anti-ETAR antibodies and their impact on renal transplant during the first year observation.MethodsWe evaluated the presence of anti-ETAR antibodies in 116 consecutive renal transplant recipients in pre- and post-transplant screening (before and in 1st, 3rd, 6th, 12th month after transplantation). Additionally, we assessed the presence of anti-HLA antibodies. Anti-ETAR antibodies were assayed by ELISA. The diagnosis of acute rejection was based on the Banff criteria.ResultsAnti-ETAR antibodies were observed in 55 (47.4%) of the analyzed recipients before transplantation. The function of renal transplant was significantly worse in the anti-ETAR(+) group compared to the anti-ETAR(?) group during the first post-transplant year. One month after transplantation the serum creatinine in anti-ETAR (+) patients (pts) was 1.86 ± 0.8 mg/dl and 1.51 ± 0.5 in anti-ETAR(?) pts (p = 0.009). Twelve months after transplantation the difference between the groups was still observed 1.70 ± 0.7 vs. 1.40 ± 0.4 (p = 0.04).Biopsy proven acute rejection was recognized in 8/55 (14.5%) in ETAR(+) and 9/61 (14.8%) in ETAR(?) patients but cases with mild to severe intimal arteritis (v1–v3) were more often observed in patients with the presence of anti-ETAR Abs 4/55 (7.2%) comparing with 1/61 (1.6%) in anti-ETAR(?) patients. The anti-ETAR antibody levels varied at different measurement intervals during the one-year follow-up.ConclusionsThe presence of anti-ETAR antibodies is associated with a worse renal transplant function during the first 12 months after transplantation. Including anti-ETAR antibodies in the diagnostics of renal transplant recipient immune status should be considered to provide comprehensive assessment of humoral alloimmunity.     

CT evaluation of patent artery after percutaneous cryoablation of renal cell carcinoma

PurposeThe purpose of this retrospective study was to determine the incidence of persistent patent artery after percutaneous cryoablation of renal cell carcinoma (RCC) and the relationship between patent arteries one month after cryoablation and early tumor progression.Materials and methodsOne hundred and fifty-nine patients (112 men, 47 women; mean age, 63.6 ± 14.6 [SD] years; age range: 21–91 years) who underwent percutaneous cryoablation for 186 RCCs (mean diameter, 1.9 ± 0.6 [SD] cm; range: 0.7–4.0 cm) were retrospectively included. After cryoablation, patients underwent contrast-enhanced computed tomography (CT) with ≤ 2-mm slice thickness within one week from cryoablation, and at one, three, and six months. The time course of patent artery in the ablated renal parenchyma after cryoablation was the primary endpoint. The relationships between patent arteries one month after cryoablation and treatment effectiveness, tumor vascularity, tumor enhancement one month after cryoablation, tumor subtype, and renal function changes were evaluated as secondary endpoints.ResultsCT showed patent arteries in the ablated renal parenchyma within one week in 166 RCCs (89.2%), at one month in 54 RCCs (29.0%), at three months in 8 RCCs (4.3%), and at six months in 2 RCCs (1.1%). The presence of patent artery one month after cryoablation was significantly associated with tumor enhancement at the same time point (P = 0.015). There was no association between patent arteries one month after cryoablation and treatment effectiveness (P = 0.693).ConclusionPatent arteries in the ablated renal parenchyma are commonly observed on CT examination after percutaneous cryoablation of RCC. However, they gradually disappear and do not require specific treatment.     

Comprehensive assessment of sensitizing events and anti-HLA antibody development in women awaiting kidney transplantation

BackgroundAlloimmunization remains a critical factor which affects the success of kidney transplantation. Patients awaiting solid organ transplantation may develop anti-HLA antibodies after pregnancies, transfusions and previous events of transplantations.AimWe evaluated the effects of different sensitizing events on the anti-HLA antibody production and the potential role of patient HLA alleles in the context of antibody development in both the overall and pregnancy sensitized groups.Material and methodsWe retrospectively stratified 411 women on waiting list for kidney transplantation by route of sensitization. The presence of anti-HLA antibodies was evaluated by Solid Phase Assay and HLA typing was performed by serological and molecular methods.ResultsIn our study population, 54% of women had anti-HLA antibodies. We found that the 51.6% of women with pregnancy only, 44% of women with transfusion only and 100% of women with a history of transplantation only developed anti-HLA antibodies. Pregnancy only resulted significantly associated with all anti-HLA antibody development such as anti-A, -B, -C, -DR, -DP as well as anti-DQB and -DQA antibodies. We investigated the influence of patient HLA alleles on the antibody development in the overall study population. Patients expressing HLA A*32 (p = 0.024, OR = 0.42), B*14 (p = 0.035, OR = 0.44), HLA-B*44 (p = 0.026, OR = 0.51) and DRB1*01 (p = 0.029, OR = 0.55) alleles produced anti-HLA antibodies less frequently compared to subjects with other alleles. In the pregnancy only group, B*14 (p = 0.010, OR = 0.12) and B*51 (p = 0.005, OR = 0.24) alleles were associated with a low risk of anti-HLA antibody development, while A*11 (p = 0.033, OR = 3.56) and DRB1*04 (p = 0.022, OR = 3.03) alleles seem to represent a higher risk.ConclusionsPregnancy still remains a strong sensitizing event in women awaiting kidney transplantation. The anti-HLA antibody development in pregnancy appears to be associated with the expression of particular HLA alleles.     

Antibody response to HBV vaccination on dialysis does not correlate with the development of deNovo anti-HLA antibodies after renal transplantation

BackgroundResponse to Hepatitis B virus (HBV) vaccination can be diminished in some (50–80%) but not all dialysis patients. We hypothesized, that the response to vaccination on dialysis may correlate with the development of anti-HLA antibodies after renal transplantation and might therefore be a valuable parameter to predict alloresponses.MethodsThe response to HBV vaccination on dialysis and the development of deNovo anti-HLA antibodies post-transplant was analyzed in 188 non-immunized renal transplant recipients. The response to HBV vaccination was evaluated by measuring the anti-HBs titer at time of transplantation. Anti-HLA antibodies post-transplant were monitored by serial measurements by means of Luminex. Acute rejection episodes, graft loss and renal dysfunction were assessed within a median follow-up of 5.5 years.ResultsOne hundred and forty-one patients (75%) exhibited an adequate immune response to HBV vaccination on dialysis. Vaccine responder (R) and none responder (NR) did not differ with respect to age, gender and BMI, while R spend significantly more time on dialysis before transplantation (4.58 ± 3.35 vs 3.23 ± 2.55 years, p = 0.033). More NR developed deNovo anti-HLA antibodies (27.7 vs 22.7%, p = 0.554) and donor-specific anti-HLA antibodies (23.4 vs 14.2%, p = 0.173) in comparison to R. Accordingly, the number of acute rejections was higher in NR as compared to R (36.1 vs 24.1%, p = 0.130) while graft survival was similar in both groups.ConclusionContrary to our hypothesis antibody response to HBV vaccination on dialysis does not predict the development of anti-HLA antibodies post transplant.     

NKT cells are important mediators of hepatic ischemia-reperfusion injury

IntroductionIRI results from the interruption then reinstatement of an organ's blood supply, and this poses a significant problem in liver transplantation and resectional surgery.In this paper, we explore the role T cells play in the pathogenesis of this injury.Materials & methodsWe used an in vivo murine model of warm partial hepatic IRI, genetically-modified mice, in vivo antibody depletion, adoptive cell transfer and flow cytometry to determine which lymphocyte subsets contribute to pathology. Injury was assessed by measuring serum alanine aminotransfersase (ALT) and by histological examination of liver tissue sections.ResultsThe absence of T cells (CD3εKO) is associated with significant protection from injury (p = 0.010). Through a strategy of antibody depletion it appears that NKT cells (p = 0.0025), rather than conventional T (CD4 + or CD8 +) (p = 0.11) cells that are the key mediators of injury.DiscussionOur results indicate that tissue-resident NKT cells, but not other lymphocyte populations are responsible for the injury in hepatic IRI. Targeting the activation of NKT cells and/or their effector apparatus would be a novel approach in protecting the liver during transplantation and resection surgery; this may allow us to expand our current criteria for surgery.     

Pretransplant serum BAFF levels are associated with pretransplant HLA immunization and renal allograft survival

BackgroundThe essential function of B cell–activating factor (BAFF) is regulating the survival and differentiation of B cells. The link between pretransplant BAFF levels and pretransplant alloimmunization and its value to predict subsequent acute antibody-mediated rejection (AMR) and outcome after renal transplantation is not fully understood.MethodsObjective of our retrospective single-center study was to determine, by ELISA analysis of pretransplant serum BAFF levels in 249 patients undergoing renal transplantation, association between preformed anti-human leukocyte antigen (HLA) antibodies, occurrence of acute antibody mediated rejection (AMR) and renal allograft survival.ResultsPretransplant serum BAFF levels were significantly higher in presensitized recipients with anti-HLA antibodies (3262 ± 2796 pg/ml) than in recipients without occurrence of anti-HLA antibodies (2252 ± 1425 pg/ml; p < 0.0001). In addition, pretransplant BAFF levels correlated with cumulative MFI values of anti-HLA antibodies (r = 0.2966, p = 0.0025). Patients with high pretransplant BAFF levels (≥ 2137 pg/ml) experienced significantly lower allograft survival rates compared to low pretransplant BAFF levels (80% vs. 91%; p = 0.01). Coexistence of high pretransplant BAFF levels and posttransplant AMR was associated with the worst allograft survival rates (56%). Relative risk (RR) for allograft loss was associated with high serum BAFF levels (RR 2.3; p = 0.02), presence of anti-HLA antibodies (RR 2.5; p = 0.007) or anti-HLA -donor-specific antibodies (DSAs) (RR 2.6; p = 0.003) before transplant and AMR post transplant (RR 2.5; p = 0.007). AMR was the strongest independent risk factor for allograft failure (RR 2.6; p = 0.03).ConclusionElevated pretransplant serum BAFF levels negatively affect renal allograft survival and represent a risk factor for allosensitization and subsequent AMR.     

Monocytic adhesion molecule expression and monocyte-endothelial cell dysfunction are increased in patients with peripheral vascular disease versus patients with abdominal aortic aneurysms

BackgroundStatin therapy is used in the medical management of patients with peripheral vascular disease (PVD) and abdominal aortic aneurysm (AAA) for the pleiotropic and anti-inflammatory benefits. We hypothesize that the inflammatory mechanisms of monocyte–endothelial cell interactions in endothelial barrier dysfunction are more significant in patients with PVD compared with those with AAA. The purpose of this study was to assess patient peripheral blood monocyte adhesion molecules by flow cytometry and monocyte-induced endothelial barrier dysfunction by using an in vitro endothelial cell layer and electric cell-substrate impedance sensing (ECIS) system.MethodsPeripheral blood was collected from patients with either PVD (ankle-brachial index <0.9, toe–arm index <0.8, or required lower extremity vascular intervention) or AAA (aortic diameter >3.0 cm). Monocytes were isolated from fresh whole blood using an accuspin-histopaque technique. The separated monocytes underwent flow cytometry analysis to evaluate the expression levels of the cell membrane adhesion molecules: CD18, CD11a/b/c, and very late antigen-4. Endothelial cell function was assessed by adding monocytes to an endothelial monolayer on ECIS arrays and coculturing overnight. Peak changes in transendothelial electrical resistance were measured and compared between patient groups.ResultsTwenty-eight monocyte samples were analyzed for adhesion molecules (PVD, 19 and AAA, 9) via flow cytometry, and 11 patients were evaluated for endothelial dysfunction (PVD, 7 and AAA, 4) via ECIS. There was no significant difference between risk factors among PVD and AAA patients except for age, where AAA patients were significantly older than PVD patients in both flow cytometry and ECIS groups (P = 0.02 and 0.01, respectively). There were significantly higher levels of adhesion molecules CD11a, CD18, and CD11c (averaged mean fluorescent intensity P values: 0.047, 0.038, and 0.014, respectively) in PVD patients compared with AAA patients. No significant difference was found for CD11b and very late antigen-4 expression (P = 0.21 and 0.15, respectively). There was significantly more monocyte–endothelial cell dysfunction in patients with PVD versus patients with AAA, with a maximal effect seen at 15 h after monocyte addition (P = 0.032).ConclusionsPatients with PVD have increased expression levels of certain monocyte adhesion molecules and greater monocyte-induced endothelial layer dysfunction compared with those with AAA. This may lead to other methods of targeted therapy to improve outcomes of these vascular patients.     

Synergism of a natural plant product,oleanolic acid with calcineurin inhibitor in prolonging islet allograft survival

BackgroundOleanolic acid (OA) is a natural plant-derived triterpenoid with potent anti-inflammatory properties. Since inflammatory cytokines released following islet transplantation hinders engraftment and long-term function, we determined the synergistic ability of OA to with Cyclosporine-A (CSA), a calcineurin inhibitor in improving islet allograft's function and survival.MethodsC57BL/6 mice were rendered diabetic using streptozotocin (200 mg/kg). BALB/c islets were transplanted under the kidney capsule alone (control) or along with administration of OA alone, CSA alone or a combination of both OA and CSA (OA + CSA). T-cell infiltration was analyzed by immunohistochemistry; cytokine concentration was analyzed by Luminex; T-cell cytokine phenotype was analyzed by ELISpot; and alloimmune response was analyzed by flow cytometry.ResultsOA + CSA markedly prolonged islet allograft survival compared to controls (37 ± 5 days vs. 8 ± 3 days). A significant decrease of CD4 + (34 ± 9 vs. 154 ± 42 cells/hpf) and CD8 + T-cellular (46 ± 22 vs. 224 ± 51 cells/hpf, p < 0.0001) infiltration into the graft in OA + CSA treated mice compared to controls. A significant decrease in T cell infiltration was demonstrated in the OA + CSA cohort over either compound application individually. An increase in anti-inflammatory molecules, IL-10 (2.4-fold) and vascular endothelial growth factor (1.6-fold), along with decreased pro-inflammatory cytokines IFN-γ, IL-1β (1.3–2.4-fold) and IL-17 (3.2-fold) was demonstrated. OA + CSA also significantly decreased the frequency of allo-specific T-cell responses. Development of antibodies against donor antigens was also delayed (39 vs 22 days; p < 0.05) in the OA + CSA cohort over administration of either agent individually.ConclusionsOA and CSA exert synergistic effect towards enhancing islet allograft survival and function. This synergistic effect resulted in markedly reduced graft infiltrating cells with attenuation of inflammatory cytokine milieu leading to impairment of both cellular and humoral alloimmune responses. Therefore, novel therapeutic approaches involving combination of OA with calcineurin-inhibitor based immunosuppressant CSA will produce potential beneficial outcomes in clinical islet transplantation.     

Effects of B cell depletion on T cell allogeneic Immune responses: A strategy to reduce allogeneic sensitization

BackgroundB cell depletion has been employed to treat antibody-mediated organ transplantation rejection, although the effects on cellular immune responses have not been extensively investigated.MethodsA model of B cell depletion used SCID/beige mice reconstituted with BALB/c splenocytes either depleted of B cells (BD) or not (BN). BD and B/N mice received C57BL/6 skin grafts and were sacrificed after 6 weeks (BD-S6 and BN-S6).ResultsRecall proliferative responses of BD-S6 splenocytes to C57BL/6 were significantly reduced compared to BN-S6, and central memory T cells' proportions (CD4⁺CD44⁺CD62L⁺ or CD8⁺CD44⁺CD62L⁺) were significantly decreased in BD-S6 spleens. Recall IFN-γ production by BD-S6 splenocytes was significantly reduced compared to BN-S6 splenocytes (p = 0.0028). Survival times of C57BL/6 heart grafts were significantly longer in SCID/beige mice reconstituted with BD-S6 splenocytes (8.5 ± 1.1 days) than for SCID/beige reconstituted with BN-S6 splenocytes (6.0 ± 1.1 days; p = 0.0006). Under cyclosporine therapy, C57BL/6 heart survival was significantly longer for SCID/beige reconstituted with BD-S6 splenocytes (17.5 ± 6.4 days) than those reconstituted with BN-S6 splenocytes (6.2 ± 1.5 days; p < 0.0001).ConclusionB cell depletion during allogeneic sensitization decreased memory T cells and recalls IFN-γ production and reduced second-set allograft rejection.     

Simultaneous liver–pancreas transplantation for cystic fibrosis-related liver disease: A multicenter experience

BackgroundDiabetes is associated with increased morbidity and mortality in patients with cystic fibrosis (CF). While liver transplantation is well established for CF-related liver disease (CFLD), the role of simultaneous liver–pancreas transplantation is less understood.MethodsWe polled 81 pediatric transplantation centers to identify and characterize subjects who had undergone simultaneous liver–pancreas transplantation and obtain opinions about this procedure in CFLD.ResultsFifty (61.7%) polled transplant centers responded and 94% reported that they would consider simultaneous liver–pancreas transplantation for CFLD and diabetes. A total of 8 patients with simultaneous liver–pancreas transplantation were identified with median follow up of 38 months. All patients had pre-existing diabetes. Exocrine and endocrine pancreatic function was initially restored in all patients with later functional loss in one patient. Body mass index Z-score increased between one year pre-transplantation and one year post-transplantation (P = 0.029).ConclusionsPatients with CFLD undergoing initial assessment for liver transplantation may benefit from consideration of simultaneous liver–pancreas transplantation.     

Mannose-binding lectin-2 and ficolin-2 gene polymorphisms and clinical risk factors for acute rejection in kidney transplantation

IntroductionThere is growing evidence that the lectin pathway is significantly associated with acute rejection. Rare studies associated both gene polymorphisms of MBL2 and FCN2 with acute rejection after kidney transplantation. The aim of the present study was to investigate the role of the lectin gene profile and clinical risk factors such as PRA level on acute rejection in kidney transplant recipients.MethodsWe prospectively analyzed 157 kidney transplant recipients with and without acute rejection. A total of 6 well-known functional single-nucleotide polymorphisms in the MBL2 gene and 5 in the FCN2 gene of the recipients were determined by gene sequencing. MBL2 and FCN2 genotypic variants were analyzed for association with the incidence of acute rejection within the first year after kidney transplantation.ResultsAfter adjusting for variables of P < 0.2, we found the differences in the incidence of acute rejection were only according to panel-reactive antibodies (odds ratios (OR) = 6.468, 95% confidence intervals (CI) = 2.017–20.740, P = 0.002) and the HH genotypes of MBL2 promoter ? 550 (OR = 2.448, 95%CI = 1.026–5.839, P = 0.044).ConclusionPanel-reactive antibodies and the HH genotypes of MBL2 promoter ? 550 have significant impacts on the risk of developing acute rejection after kidney transplantation.     

Biphasic bioresorbable scaffold (TruFit Plug®) for the treatment of osteochondral lesions of talus: 6- to 8-year follow-up

BackgroundThe ideal treatment of osteochondral lesions of the talus (OLT) is debatable. The TruFit plug has been investigated as a potential treatment method for osteochondral defects. This is a biphasic scaffold designed to stimulate cartilage and subchondral bone formation. The purpose of this retrospective study was to investigate the long-term functional and MRI outcomes of the TruFit Plug for the treatment of OLT.MethodsTwelve consecutive patients treated from March 2007 to April 2009 for OLT were evaluated. Clinical examination included the American Orthopaedic Foot and Ankle Society (AOFAS) ankle score and the visual analog scale (VAS) for pain. MRI scans were optained pre-treatment and at last follow-up. The Magnetic Resonance Observation of Cartilage Repair Tissue (MOCART) score was used to assess cartilage incorporation.ResultsMean follow-up was 7.5 years (range, 6.5–8.7 years). The average age was of 38.6 years (range, 22–57 years). The sex ratio between males and females was 3:1 (9 males, 3 females). The mean AOFAS score improved from a preoperative score of 47.2 ± 10.7 to 84.4 ± 8 (p < 0.05). According to the postoperative AOFAS scores 1 case obtained excellent results, 9 were classified as good, and 2 were fair. VAS score improved from a preoperative value of 6.9 ± 1.4 points to 1.2 ± 1.1 points at last follow-up (p < 0.05). The MOCART score for cartilage repair tissue on postoperative MRI averaged 61.1 points (range, 25–85 points).ConclusionsThe long-term results suggest that the technique of Trufit Plug for OLT is safe and demonstrates good post-operative scores including improvement of pain and function, with discordant MRI results. However, randomized controlled clinical trials comparing TruFit Plug with an established treatment method are needed to improve synthetic biphasic implants as therapy for osteochondral lesions.Level of evidence: Retrospective case series, Level IV.     

The efficacy of dendritic cell vaccine for newly diagnosed glioblastoma: A meta-analysis of randomized controlled studies

IntroductionThe efficacy of dendritic cell vaccine to treat glioblastoma remained elusive and therefore we conducted a meta-analysis to explore the influence of dendritic cell vaccine on treatment efficacy of glioblastoma.MethodsPubMed, EMbase, Web of science, EBSCO and Cochrane library databases have been searched through October 2020, and we included randomized controlled trials (RCTs) assessing the efficacy of dendritic cell vaccine for glioblastoma.ResultsFour RCTs and 267 patients were included in the meta-analysis. Compared to control group for glioblastoma, dendritic cell vaccine demonstrated no obvious impact on overall survival (HR = 0.59; 95% CI = 0.34 to 1.04; P = 0.07), progression-free survival (PFS, HR = 0.72; 95% CI = 0.52 to 1.00; P = 0.05), nervous system disorders (OR = 0.61; 95% CI = 0.29 to 1.29; P = 0.20), or adverse events (OR = 1.44; 95% CI = 0.82 to 2.50; P = 0.20).ConclusionsDendritic cell vaccine may be not effective to treat glioblastoma.     

Utilidad de la diferencia venoarterial de PCO2 como predictor de complicaciones en el postoperatorio inmediato del trasplante hepático

ObjectiveTest whether the development of abnormal venous-to arterial CO₂ difference (ΔPCO₂) during the early phases of postoperative care after a liver transplantation is related to multi-organ dysfunction and outcomes.Materials and methodsProspective cohort study accomplished in a mixed intensive care unit at a university hospital. We included 150 eligible patients after a liver transplantation between 2015 and 2018.Patients were classified in 4 predefined groups according to the ΔPCO₂ evolution during the first 6 h of resuscitation: 1) persistently normal ΔPCO₂ (normal at T0 and T6); 2) decreasing ΔPCO₂ (high at T0, normal at T6); 3) increasing ΔPCO₂ (normal at T0, high at T6); and 4) persistently high ΔPCO₂ (high at T0 and T6). Multiorgan dysfunction at day-3 was compared for predefined groups and a Kaplan Meier curve was constructed to show the survival probabilities using a log-rank test to evaluate differences between groups. A Spearman-rho was used to test the agreement between cardiac output and ΔPCO₂.ResultsThere were no significant differences between the study groups regarding higher SOFA scores at day-3 (P = 0.86), Δ-SOFA (P = 0.088), as well as global mortality rates (χ² = 5.72; P = 0.126) and mortality rates at day-30 (χ² = 2.23; P = 0.5252).A significantly poor inverse agreement between cardiac output and ΔPCO₂ was observed (rho de Spearman ?0,17; P = 0,002) at different points of resuscitation.ConclusionsAfter a liver transplantation, central venous-to-arterial CO₂ difference was not associated with survival or postoperative adverse outcomes in a critical care patients population.     

Percutaneous thermal ablation for renal cell carcinoma in patients with Birt–Hogg–Dubé syndrome

PurposeThe purpose of this study was to analyze the outcome of patients with Birt–Hogg–Dubé (BHD) syndrome who underwent percutaneous thermal ablation of renal cell carcinoma (RCC).Materials and methodsSix patients with genetically proven BHD syndrome who underwent one or more sessions of percutaneous thermal ablation for the treatment of RCC were included. There were 4 men and 2 women, with a mean age of 57.3 ± 7.5 [SD] years (range: 44–67 years). A total of 29 RCCs (1–16 tumors per patient) were treated during 20 thermal ablation sessions (7 with radiofrequency ablation and 13 with cryoablation). Outcomes of thermal ablation therapy were assessed, including technical success, adverse events, local tumor progression, development of metastases, survival after thermal ablation, and changes in renal function.ResultsTechnical success was achieved in all ablation sessions (success rate, 100%). No grade 4 or 5 adverse events were observed. All patients were alive with no distant metastasis during a median follow-up period of 54 months (range: 6–173 months). No local tumor progression was found. The mean decrease in estimated glomerular filtration rate during follow-up was 10.7 mL/min/1.73 m². No patients required dialysis or renal transplantation.ConclusionRadiofrequency ablation and cryoablation show promising results for the treatment of RCCs associated with BHD syndrome. Percutaneous thermal ablation may be a useful treatment option for this rare hereditary condition.     

The Efficacy and Safety of Different Sericin Doses for Pleurodesis

BackgroundThe aim of present study is to compare the effectiveness, side-effect potential of different doses of sericin pleurodesis.MethodsAdult, male, 12-week-old, Wistar-albino rats (n = 52), were randomly-divided into four-groups, referred to A, B, C and D. Sericin was administrated at different doses through left thoracotomy, with 15 mg sericin to Group-A, 30 mg to Group-B and 45 mg to Group-C. Group-D was assigned as control group. The rats were sacrificed 12 days later. Left-hemithorax, heart, liver and kidney were examined pathologically.ResultsNo foreign body reaction in the parenchyma was observed in any of the rats, while emphysema was least common in Group-B (P < .05). Multi-layer mesothelium of both pleura was most common in Group-B, while fibrosis and fibrin organization within the visceral-pleura was more successful in all of sericin treated groups than in control group (P < .05), with neither Group-A, Group-B nor Group-C being superior to each other. In the examination of collagen fibers using Masson's trichrome, “dense collagen fibers” were found in all three sericin treated groups, and differences between Groups-A, -B, -C and the control group were significant (P < .05). The probability of observing pyknotic nucleus and balloon degeneration in liver increased with increasing sericin doses (P < .05). Glomerular degeneration in kidney and the findings of pericarditis were most common in Group-C (P < .05).ConclusionThe target should be to maximize efficacy while minimizing the likelihood of side-effects. The intrapleural administration of sericin 30 mg performs better due to multi-layer mesothelial reaction being higher and emphysema being lower in Group-B, to the fewer side-effects affecting the kidney and heart, and liver toxicity not being higher.     

Retreatment by antithymocyte globulin for second kidney transplantation: Efficacy,tolerance and safety

BackgroundIt is unknown whether kidney transplant patients who receive rabbit antithymocyte globulin (rATG) become immunized against rabbit antibodies, leading to reduced efficacy, or are at higher risk of cytomegalovirus infection or post-transplant lymphoproliferative disorder (PTLD) on retreatment. The efficacy and tolerance of rATG when used as induction for the second time in patients undergoing retransplantation have not been evaluated.MethodsIn a retrospective case–control study, 54 retransplanted patients who received rATG (Thymoglobulin) induction for the second time during 2004–2010 were compared to a matched cohort of 108 patients receiving rATG induction for a first kidney transplantation during the same period. Maintenance treatment was similar in both groups.ResultsMedian follow-up was 45.8 months and 47.3 months in the second and first treatment groups, respectively. No differences were observed between the two groups in terms of leukocyte, lymphocyte or platelet depletion. Dose and duration of rATG treatment were similar in both groups, suggesting a similar tolerance profile. Cytomegalovirus infection (including primoinfection and reactivation) occurred in 4/54 retreated patients versus 22/108 controls (p = 0.108). Use of cytomegalovirus prophylaxis was similar between groups. PTLD occurred in one control patient and no retreated patients.ConclusionA second course of rATG induction results in similar lymphocyte depletion and is as well tolerated as a first course. The incidence of cytomegalovirus infection and post-transplant lymphoproliferative disease was not increased during retreatment. Further studies are required to evaluate specific T cell subpopulation depletion and compare long-term outcome in patients receiving a second induction with rATG.     

Recipient body size does not matter in pediatric liver transplantation

Background and purposeIt is controversial whether small size recipient is associated with adverse outcome in liver transplantation. This study aims to evaluate the outcomes of pediatric liver transplantation according to body weight of recipients.MethodsLiver transplant recipients (age < 18 years, from 1993 to 2011) were studied retrospectively. They were categorized according to the body size at the time of transplantation (A: < 6 kg; B: between 6 kg to 10 kg; C: > 10 kg).ResultsA total of 113 patients (83 LDLTs and 30 DDLTs) were studied. Thirteen (11.5%) belonged to group A, 56 (49.6%) belonged to group B, and 44 (38.9%) belonged to group C. The best graft and patient survivals were found in group A (Figs. 1 and 2), and none of the patients required re-laparotomy for general surgical complications, while 32 patients (32%) in groups B and C did. Regarding transplant-related complications, although group A patients had the highest incidence of biliary tract complications (38.5%, n = 5), the incidence of vascular complications (hepatic artery: 7%, portal vein: 0%, hepatic vein: 0%) in this group was the lowest among the three groups.ConclusionOutcomes of small-sized recipients are not inferior. Less technical-related vascular complications, which may lead to early graft loss, were observed. This could be patient-related (less advanced cirrhosis) or surgeon-related (additional attention paid).