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Review a series of 22 patients below the age of 16 affected by primary bone tumors of the spine who underwent en bloc resection, and describe the clinical presentation, tumor characteristics, results and complications associated with the surgical treatment, underlining the specific issues related to a younger age. We performed a review of all patients

Chronic kidney disease has reached pandemic levels and poses a substantial public health burden. Unfortunately, available therapies lack efficacy in preventing progression to its end-stage phase. Regenerative medicine promises to restore the function of diseased organs, among which the kidney, through two possible approaches: firstly, the maximization of the innate ability of tissues to repair or regenerate the following injury; secondly, the ex vivo bio-fabrication of the organ in question. This chapter illustrates the state of the art of the research that proposes the use of extracellular matrix-based biomaterials as a template for the bioengineering, regeneration, and repair of the kidney.

Following simultaneous pancreas-kidney transplantation (SPKT), survival outcomes are reported as equivalent in patients with detectable pretransplant C-peptide levels (Cp+) and a "type 2″ diabetes mellitus (DM) phenotype compared to type 1 (Cp negative [Cp-]) DM. We retrospectively compared 46 Cp+ patients pretransplant (≥2.0 ng/mL, mean 5.4 ng/mL) to 46 Cp- (level 0.5 ng/mL) case controls matched for recipient age, gender, race, and transplant date. Early outcomes were comparable. Actual 5-year patient survival (91% versus 94%), kidney graft survival (69% versus 86%, p = .15), and pancreas graft survival (60% versus 86%, p = .03) rates were lower in Cp+ versus Cp- patients, respectively. The Cp+ group had more pancreas graft failures due to insulin resistance (13% Cp+ versus 0% Cp-, p = .026) or rejection (17% Cp+ versus 6.5% Cp-, p = .2). Post-transplant weight gain 5 kg occurred in 72% of Cp+ versus 26% of Cp- patients (p = .0001). In patients with functioning grafts, mean one-year post-transplant HbA1c levels (5.0 Cp+ versus 5.2% Cp-) were comparable, whereas Cp levels were higher in Cp+ patients (5.0 Cp+ versus 2.6 ng/mL Cp-). In this matched case-control study, outcomes were inferior in Cp+ compared to Cp- patients following SPKT, with post-transplant weight gain, insulin resistance, and rejection as potential mitigating factors.

STUDY DESIGN Retrospective case-control study. OBJECTIVE The aim of this study was to evaluate the prevalence of pseudarthrosis following antepsoas (ATP) lumbar and lumbosacral fusions. SUMMARY OF BACKGROUND DATA Pseudarthrosis is a feared complication following spinal fusions and may affect their clinical outcomes. To date there are no sufficient data on the fusion rate following ATP lumbar and lumbosacral arthrodesis. METHODS This is a retrospective review of 220 patients who underwent lumbar minimally invasive antepsoas (MIS-ATP) fusions between January 2008 and February 2019 who have at least 1-year postoperative computed tomography (CT) follow-up scans. Fusion was graded using CT scans imaging and adopting a 1-4 grading scale (1, definitely fused; 2, likely fused; 3, likely not fused; 4, definitely not fused/nonunion). Grades 3 or 4 indicate pseudarthrosis. RESULTS A total of 220 patients (average age: 66 years, 82 males (37.2%), and 127 (57.7%) smokers) were included. Eight patients (3.6%) developed pseudarthrosis. A total of 693 discs were addressed using the ATP approach. Of those, 681 (98.3%) were considered fused (641 levels [92.5%] were "definitely fused" and 40 levels [5.8%] were "Likely fused") and 12 discs (1.7%) developed pseudarthrosis (seven levels [1.0%] were "likely not fused" and five levels (0.7%) were "definitely not fused"). The highest rate of pseudarthrosis was found at L5-S1 (4.8%) compared to the L1-L5 discs (0-2%). Of 127 smokers, six developed pseudarthrosis (odds ratio = 2.3, P = 0.3). The fusion rates were 95.3% and 97.8% for smokers and nonsmokers, respectively. Of the eight patients who developed pseudarthrosis, only four (50%) were symptomatic, of whom two (25%) required revision surgery. Both of these patients were smokers. The overall revision rate due to pseudarthrosis was 0.9% (two of 220 patients). CONCLUSION The MIS-ATP technique results in a high fusion rate (96.4% of patients; 98.3% of levels). Pseudarthrosis was noted mostly at the L5-S1 discs and in smokers.Level of Evidence: 4.

Background The study purpose was to analyze outcomes in recipients of pediatric dual en bloc (PEB) kidneys from small pediatric donors (SPDs, age ≤ 3 years) and dual kidney transplants (KTs) from adult marginal deceased donors (DDs) in the context of the Kidney Donor Profile Index (KDPI). Study Design This was a single center retrospective review. Recipient selection included primary transplant, low BMI, low immunologic risk, and informed consent. All patients received antibody induction with FK/MPA/± prednisone. Results From 2002 to 2015, we performed 34 PEB and 73 adult dual KTs. Mean donor ages were 17 months for the PEB and 59 years for the dual KTs; mean KDPIs were 73% for PEB and 83% for dual KT, and mean cold ischemia times were 21.0 hours for PEB and 26.5 hours for dual KT. Adult dual KT recipients were older (mean age 38 years for PEB and 60 years for dual KT) and had shorter waiting times (mean 25 months for PEB and 12 months for dual KT). With a mean follow-up of 7.6 years, actual patient survival (88% for PEB and 62% for dual KT) and graft survival (71% for PEB and 44% for dual KT) rates were higher in PEB compared with dual KT. Death-censored kidney graft survival rates were 77% for PEB and 58% for dual KT. Delayed graft function (DGF) rates were 15% for PEB and 23% for dual KT; incidences of DGF in single kidney transplantations from SPDs and adult nonmarginal DDs were 20% and 32%, respectively. Based on actual 5-year graft survival rates, the adjusted KDPIs for dual PEB and dual KTs were 3% and 60%, respectively. Conclusions Acceptable mid-term outcomes are associated with PEB and adult dual KTs, which may expand the donor pool and prevent kidney discard. The KDPI is inaccurate for predicting outcomes from either PEB from SPDs or dual KT from adult marginal DDs, which may prevent acceptance of these organs.

Background En bloc surgery is the mainstay treatment for primary malignant bone tumors, as well as in the cervical spine. Unfortunately, literature on the topic is limited to case reports and small series. Methods We reviewed all patients affected by primary cervical spine bone tumors treated with en bloc surgeries from 1996 to 2016 and identified 30 eligible cases. We evaluated the clinical presentation and tumor characteristics and reported surgical results, complications, recurrence, and survival rates. Results Only 17 of 30 patients had not been previously treated at presentation. Osteosarcoma and chordoma were the most frequent tumors, and pain was reported in all cases. En bloc spondylectomy, hemispondylectomy, and posterior arch en bloc resection were performed in 16, 12, and 2 patients, respectively. The obtained margin was adequate (wide and marginal) in 60% of cases and intralesional in the remaining cases. Two deaths occurred in the immediate postoperative period. Neurological deterioration, dural tear, and dysphagia were the most frequent complications. The 5-year local recurrence-free survival was 70.4%. The recurrence rate was 38.5% and 11.7% in previously and non–previously treated patients, respectively (χ2: 2.94; P = 0.086). Overall survival at 5 years was 58% and 47% for all series and malignant tumors, respectively. Conclusion Primary cervical spine bone tumors present a difficult approach. Findings suggest that patients treated with en bloc surgery show recurrence and survival rates comparable to the same tumors located in the thoracolumbar spine.

Funder: Fondazione Pisa, Pisa, Italy; Id: http://dx.doi.org/10.13039/100007368, Funder: Tuscany Region, Italy; Id: http://dx.doi.org/10.13039/501100009888, Funder: Pisa University Hospital, Pisa, Italy, Funder: University of Pisa, Pisa, Italy; Id: http://dx.doi.org/10.13039/501100007514, The First World Consensus Conference on Pancreas Transplantation provided 49 jury deliberations regarding the impact of pancreas transplantation on the treatment of diabetic patients, and 110 experts' recommendations for the practice of pancreas transplantation. The main message from this consensus conference is that both simultaneous pancreas-kidney transplantation (SPK) and pancreas transplantation alone can improve long-term patient survival, and all types of pancreas transplantation dramatically improve the quality of life of recipients. Pancreas transplantation may also improve the course of chronic complications of diabetes, depending on their severity. Therefore, the advantages of pancreas transplantation appear to clearly surpass potential disadvantages. Pancreas after kidney transplantation increases the risk of mortality only in the early period after transplantation, but is associated with improved life expectancy thereafter. Additionally, preemptive SPK, when compared to SPK performed in patients undergoing dialysis, appears to be associated with improved outcomes. Time on dialysis has negative prognostic implications in SPK recipients. Increased long-term survival, improvement in the course of diabetic complications, and amelioration of quality of life justify preferential allocation of kidney grafts to SPK recipients. Audience discussions and live voting are available online at the following URL address: http://mediaeventi.unipi.it/category/1st-world-consensus-conference-of-pancreas-transplantation/246.

The clinical benefit of islet allo- and autotransplantation is limited by a massive loss of implanted cells immediately postimplantation. Episodes of more subtle beta cell loss occur during the natural history of type 1 diabetes and at later time points posttransplantation. Our understanding of the disease and the development of innovative therapies to preserve or restore a sufficient beta-cell mass would benefit from noninvasive measures to detect and quantify episodes of beta-cell destruction. This can be assessed indirectly by monitoring changes in functional beta-cell mass, most precisely and accurately by hyperglycemic clamp test. Non-secreted beta cell-selective proteins, unmethylated gene regions, and microRNAs (miRs) have been validated as circulating markers of ongoing beta-cell damage. In the context of islet transplantation, 65 kDa-glutamate decarboxylase and miR-375 have been most closely associated with beta-cell loss and subsequent graft function.

Diabetes is a debilitating disease affecting millions of people and leading to billions of dollars in healthcare expenditures. While exogenous insulin therapy can be highly effective, it does not completely replace the function of pancreatic islets and is fraught with complications when used long term for diabetes management. Islet transplantation has a high potential to treat these patients, especially type 1 diabetics who have lost a pancreatic function due to autoimmunity against these cells, but fundamental challenges specific to an effective encapsulation system need to be overcome. Macroencapsulation devices offer an effective delivery platform, as they protect the islets from the immune environment of the recipient, allow for less-invasive treatment (compared to organ transplant), reduce cost, can accommodate many sources of cells (e.g., allogenic, xenogenic, iPS) and have been shown to produce exogenous insulin independence. Although encapsulation devices have met several challenges, the synergistic convergence of knowledge from stem cell biology, immunology material science, and nanotechnology will allow us to get closer to the objective of achieving long-term survival and function of encapsulated cells, ease of application, and ultimately, a cost-effective treatment for patients.

Pancreas benching preparation is of crucial importance for the success of transplantation. It is a complex and time-consuming procedure requiring stapling, many suture ligations, and vessel reconstruction. Organ damage occurs in more than 50% of pancreas procurement. Therefore, a profound knowledge of the pancreas anatomy and variations is necessary to avoid and to recognize lesions during both pancreas procurement and bench work. The back-table preparation of the pancreas involves the following stages: (1) inspection of the graft, (2) duodenal dissection/shortening with stapler, (3) suture/ligation of the vessels at the root of the mesentery and inferior mesenteric vein, (4) removal of the excess fat surrounding the pancreas and ligation of small vessels and lymphatics, (5) limited dissection and mobilization of the splenic and superior mesenteric arteries and portal vein and removal of excess ganglion tissue, (6) vascular reconstruction with the Y graft, and (7) spleen can be removed before or after graft implantation.

Inflammatory bowel disease (IBD), namely, Crohn's disease and ulcerative colitis, remains a grievous and recalcitrant problem incurring significant human and health care costs, even in consideration of the growing incidence. Initial goals of care aimed to achieve the induction and maintenance of clinical remission. The advent of novel treat-to-target approaches using patient stratification, early introduction of immunosuppressants and rapid escalation to biologics or early use of combination therapy has refocused the goals of care toward the achievement of mucosal healing. This is in an attempt to preserve intestinal function, decrease hospitalization and surgery rates and improve the quality of life of affected patients. Cellular therapeutics for the treatment of IBD offers an unprecedented opportunity to change the current paradigm from single-targeted to systems-targeted therapy, trying to dampen the whole inflammatory cascade instead of a only molecule. Therefore, as we move forward, the importance of designing informative and possibly adaptive trial designs, standardizing methodologies, harmonizing goals of therapy and evaluating methods cannot be underemphasized. In this article, we review the current literature on the application of mesenchymal stromal cells for the treatment of IBD in an effort to establish a consensus on designing efficient and consistent clinical trials for the intravenous use of this cellular therapy in IBD.

Background The need to expand the organ donor pool remains a formidable challenge in kidney transplantation (KT). The use of expanded criteria donors (ECDs) represents one approach, but kidney discard rates are high because of concerns regarding overall quality. Dual KT (DKT) may reduce organ discard and optimize the use of kidneys from marginal donors. Study design We conducted a single-center retrospective review of outcomes in adult recipients of DKTs from adult marginal deceased donors (DD) defined by limited renal functional capacity. If the calculated creatinine clearance in an adult DD was

Bladder cancer (BCA) is relatively common and potentially recurrent/progressive disease. It is also costly to detect, treat, and control. Definitive diagnosis is made by examination of urine sediment, imaging, direct visualization (cystoscopy), and invasive biopsy of suspect bladder lesions. There are currently no widely-used BCA-specific biomarker urine screening tests for early BCA or for following patients during/after therapy. Urine metabolomic screening for biomarkers is costly and generally unavailable for clinical use. In response, we developed Raman spectroscopy-based chemometric urinalysis (Rametrix (TM)) as a direct liquid urine screening method for detecting complex molecular signatures in urine associated with BCA and other genitourinary tract pathologies. In particular, the Rametrix(TM)screen used principal components (PCs) of urine Raman spectra to build discriminant analysis models that indicate the presence/absence of disease. The number of PCs included was varied, and all models were cross-validated by leave-one-out analysis. In Study 1 reported here, we tested the Rametrix (TM) screen using urine specimens from 56 consented patients from a urology clinic. This proof-of-concept study contained 17 urine specimens with active BCA (BCA-positive), 32 urine specimens from patients with other genitourinary tract pathologies, seven specimens from healthy patients, and the urinalysis control Surine(TM). Using a model built with 22 PCs, BCA was detected with 80.4% accuracy, 82.4% sensitivity, 79.5% specificity, 63.6% positive predictive value (PPV), and 91.2% negative predictive value (NPV). Based on the number of PCs included, we found the Rametrix(TM)screen could be fine-tuned for either high sensitivity or specificity. In other studies reported here, Rametrix(TM)was also able to differentiate between urine specimens from patients with BCA and other genitourinary pathologies and those obtained from patients with end-stage kidney disease (ESKD). While larger studies are needed to improve Rametrix(TM)models and demonstrate clinical relevance, this study demonstrates the ability of the Rametrix(TM)screen to differentiate urine of BCA-positive patients. Molecular signature variances in the urine metabolome of BCA patients included changes in: phosphatidylinositol, nucleic acids, protein (particularly collagen), aromatic amino acids, and carotenoids. Center for Innovative Technology [CP15015-LS]; Virginia Tech Foundation; HATCHUnited States Department of Agriculture (USDA) [VA-160057] This research was funded in part the Center for Innovative Technology (award CP15015-LS), the Virginia Tech Foundation, and HATCH (project VA-160057). These funders provided support in salaries for authors (RSS) and materials. They had no role in study design, data collection and analysis, the decision to publish, and preparation of the manuscript. RSS and JLR are unsalaried co-founders of DialySensors, Inc., which was involved with study design, data collection and analysis, the decision to publish, and preparation of the manuscript.

Raman Chemometric Urinalysis (RametrixTM) was used to discern differences in Raman spectra from (i) 362 urine specimens from patients receiving peritoneal dialysis (PD) therapy for end-stage kidney disease (ESKD), (ii) 395 spent dialysate specimens from those PD therapies, and (iii) 235 urine specimens from healthy human volunteers. RametrixTM analysis includes spectral processing (e.g., truncation, baselining, and vector normalization); principal component analysis (PCA); statistical analyses (ANOVA and pairwise comparisons); discriminant analysis of principal components (DAPC); and testing DAPC models using a leave-one-out build/test validation procedure. Results showed distinct and statistically significant differences between the three types of specimens mentioned above. Further, when introducing "unknown" specimens, RametrixTM was able to identify the type of specimen (as PD patient urine or spent dialysate) with better than 98% accuracy, sensitivity, and specificity. RametrixTM was able to identify "unknown" urine specimens as from PD patients or healthy human volunteers with better than 96% accuracy (with better than 97% sensitivity and 94% specificity). This demonstrates that an entire Raman spectrum of a urine or spent dialysate specimen can be used to determine its identity or the presence of ESKD by the donor.

Beta cell replacement has the potential to restore euglycemia in patients with insulin dependent diabetes. While great progress has been made in establishing allogeneic islet transplantation from deceased donors as the standard of care for those with the most labile diabetes, it is also clear that the deceased donor organ supply cannot possibly treat all those who could benefit from restoration of a normal beta cell mass, especially if immunosuppression were not required. Against this background, the International Pancreas and Islet Transplant Association (IPITA) in collaboration with the Harvard Stem Cell Institute (HSCI), the Juvenile Diabetes Research Foundation (JDRF), and the Helmsley Foundation held a 2-day Key Opinion Leaders Meeting in Boston in 2016 to bring together experts in generating and transplanting beta cells derived from stem cells. The following summary highlights current technology, recent significant breakthroughs, unmet needs and roadblocks to stem-cell-derived beta cell therapies, with the aim of spurring future preclinical collaborative investigations and progress toward the clinical application of stem cell-derived beta cells.

Objective To test the hypothesis that gene expression profiling in peripheral blood from patients who have undergone kidney transplantation (KT) will provide mechanistic insights regarding graft repair and regeneration. Background Renal grafts obtained from living donors (LD) typically function immediately, whereas organs from donation after cardiac death (DCD) or acute kidney injury (AKI) donors may experience delayed function with eventual recovery. Thus, recipients of LD, DCD, and AKI kidneys were studied to provide a more complete understanding of the molecular basis for renal recovery. Methods Peripheral blood was collected from LD and DCD/AKI recipients before transplant and throughout the first 30 days thereafter. Total RNA was isolated and assayed on whole genome microarrays. Results Comparison of longitudinal gene expression between LD and AKI/DCD revealed 2 clusters, representing 141 differentially expressed transcripts. A subset of 11 transcripts was found to be differentially expressed in AKI/DCD versus LD. In all recipients, the most robust gene expression changes were observed in the first day after transplantation. After day 1, gene expression profiles differed depending upon the source of the graft. In patients receiving LD grafts, the expression of most genes did not remain markedly elevated beyond the first day post-KT. In the AKI/DCD groups, elevations in gene expression were maintained for at least 5 days post-KT. In all recipients, the pattern of coordinate gene overexpression subsided by 28 to 30 days. Conclusions Gene expression in peripheral blood of AKI/DCD recipients offers a novel platform to understand the potential mechanisms and timing of kidney repair and regeneration after transplantation.

In the past, type 2 diabetes mellitus (T2DM) was a contraindication for simultaneous pancreas-kidney transplantation (SPKT) even though it was generally accepted to be an effective treatment option for selected patients with type 1 DM (T1DM) and advanced chronic kidney disease. However, because there may be tremendous overlap in the clinical presentations of T1DM versus T2DM, the presence of detectable C-peptide is no longer considered reliable in determining DM “type.” Experiences with SPKT in uremic patients with detectable pretransplant C-peptide levels with a type 2 diabetes phenotype (older age of onset of DM and older age at transplant, shorter duration of insulin-requiring DM, higher body weight/BMI, higher proportion of African-Americans) have demonstrated outcomes equivalent to those with T1DM although clearly a more robust selection bias exists for patients with presumed T2DM. The success of SPKT in this setting provides evidence that the pathophysiology of T2DM is heterogeneous and not related exclusively to insulin resistance. The purpose of this review is to summarize evidence that appropriately selected uremic patients with T2DM may benefit from SPKT, with a focus on recipient selection in order to optimize outcomes.

Purpose of review Solitary deceased donor kidney and simultaneous pancreas and kidney (SPK) transplantation are the two most common transplant procedures performed for patients with diabetes and uremia, vastly outnumbering all other organ replacement options. Given the improvement in outcomes for solitary pancreas transplantation, the higher mortality for diabetic patients on the waiting list, and the growing shortage of organs (particularly kidneys) for transplantation, the use of living donors for this complex patient population should be more common. Recent findings Yet, despite some clear advantages, sequential pancreas after live donor kidney transplant and especially the combined procedure, simultaneous pancreas (from a deceased donor) and living donor kidney transplantation are relatively uncommon. Summary Possible reasons for the infrequent use of these options and methods for increasing the use of living donor kidneys for the diabetic and uremic patient are presented.

Study Design Technique and applications. Objectives To define the anatomy, biomechanics, indications, and surgical technique of the true Ponte osteotomy. Summary of Background Data The Ponte osteotomy, originally developed for thoracic kyphosis, was the first one to obtain posterior shortening of the thoracic spine, maintaining the anterior column load-sharing capacity. It has become a widely applied technique in various types of spine deformities and a frequent topic of presentations at meetings and in scientific articles. Several of them offer unquestionable evidence of an incorrect execution, with consequently distorted outcomes and erroneous conclusions. A clearing up became essential. Methods Our original experience is based on a series of 240 patients with thoracic hyperkyphosis operated in the years 1969-2015, at first with a standard posterior Harrington technique and then by using the Ponte osteotomy with different instrumentations. A series of 78 of them, operated in the years 1987-1997, who had Ponte osteotomies at every level, is presented. Results The average preoperative kyphosis has been corrected from 80° (range 61°-102°) to 31° (range 15°-50°) by a substantial posterior shortening. Conclusions A number of publications use the term Ponte osteotomy loosely for by far incomplete resections and mixing it up with Smith-Petersen's osteotomy. The true Ponte osteotomy is capable of producing marked flexibility in extension, flexion and rotation, justifying its wide use in thoracic deformities, mainly in scoliosis. An exact performance of the osteotomy with adequate bony resections, including the laminae, is an absolute condition to take full advantage of its properties. Level of Evidence Level IV, therapeutic study.

Numerous technical vascular complications may occur during and following renal transplant that may impact graft survival and patient morbidity, but renal arterial thrombosis is perhaps the most devastating, as it is often difficult to identify vascular occlusion in sufficient time to prevent infarction and loss of the allograft. This chapter will focus on arterial thrombosis because the subject is extremely pertinent to the field of regenerative medicine and the attempts to fabricate organoids for transplant purposes.

The first successful kidney transplantation between identical twins, performed in Boston in 1954, opened the clinical transplant era. Ever since, kidney transplantation has become one of the milestones of the recent history of medicine, whilst saving millions of lives. Although the nature of this extraordinary accomplishment is multifactorial, the successful outcome of a renal transplant begins with an impeccable surgery. This chapter will illustrate the state of the art of kidney transplant surgery in the recipient.

Allograft nephrectomy (AN) is not without morbidity following graft failure (GF) in kidney transplantation (KT). Single center retrospective review of all adult patients undergoing AN following KT, including a subset of patients who underwent pre-operative angiographic kidney embolization (PAKE). Over a 104 month period, 853 adult patients underwent deceased donor KT. With a median follow-up of 3.5 years, 174 patients (20.4 %) developed GF and 38/174 (21.8 %) underwent AN. The rate of AN was higher in patients with delayed graft function [DGF, Odds Ratio (OR) 2.15, p = 0.023] and early GF (OR 1.7, p = 0.064). For patients undergoing PAKE (n = 13, mean timing of AN 27.5 months post-KT), the estimated intra-operative blood loss was reduced from a mean of 375 ± 530 to 100 ± 162 ml (p

Introduction The study purpose was to analyze 5-year outcomes in a prospective, randomized trial of alemtuzumab (ALEM) versus rabbit antithymocyte globulin (rATG) induction in simultaneous kidney–pancreas transplantation (SKPT). Patients and Methods From February 2005 through October 2008, a total of 46 SKPTs (45 portal-enteric drainage) were prospectively randomized to receive either single-dose ALEM (30 mg intraoperatively) or multiple-dose rATG antibody induction (starting intraoperatively, minimum of 3 doses administered) with tacrolimus/mycophenolate and/or steroids. Results Of 222 kidney transplant patients enrolled in the study, 46 received SKPTs; 28 (61%) received ALEM and 18 (39%) received rATG induction. Follow-up ranged from 54 to 98 months (mean, 69 months). There were no significant differences between the 2 groups in 5-year patient (82% ALEM vs 89% rATG), kidney graft (79% ALEM vs 72% rATG), or pancreas graft (64% ALEM vs 56% rATG) survival rates. Death-censored kidney (90% ALEM vs 75% rATG) and pancreas (71% ALEM vs 56% rATG) graft survival rates were likewise comparable (both, P = NS). Acute rejection (21% ALEM vs 44% rATG; P = .11) and major infection (39% ALEM vs 67% rATG; P = .13) rates were slightly lower in the ALEM group; cytomegalovirus infections were significantly lower (0% ALEM vs 17% rATG; P = .05). The incidence of late acute rejection was low in both groups. There were no differences in early pancreas thromboses (3.6% ALEM vs 11% rATG), postoperative bleeding (11% ALEM vs 0% rATG), other surgical complications, or readmissions between groups. In patients with functioning grafts, 5-year mean serum creatinine (1.4 ALEM vs 1.6 mg/dL rATG), calculated abbreviated Modification of Diet in Renal Disease glomerular filtration rate (55 ALEM vs 52 mL/min/1.73 m 2 rATG), glycosylated hemoglobin (both 5.4%), and C-peptide (2.2 ALEM vs 2.3 ng/mL rATG) levels were similar. Conclusions Single-dose ALEM and multiple dose rATG induction provided similar medium-term patient, kidney, and pancreas graft function and survival rates. ALEM induction may be associated with less acute rejection and major infection over the long term.

Emerging technologies in regenerative medicine have the potential to restore the β-cell compartment in diabetic patients, thereby overcoming the inadequacies of current treatment strategies and organ supply. Novel approaches include: 1) Encapsulation technology that protects islet transplants from host immune surveillance; 2) stem cell therapies and cellular reprogramming, which seek to regenerate the depleted β-cell compartment; and 3) whole-organ bioengineering, which capitalizes on the innate properties of the pancreas extracellular matrix to drive cellular repopulation. Collaborative efforts across these subfields of regenerative medicine seek to ultimately produce a bioengineered pancreas capable of restoring endocrine function in patients with insulin-dependent diabetes.

Background. Liver transplantation (LT) is performed for hemangiosarcoma (HAS) despite disappointing results. Methods. Retrospective study of 14 males and 8 females reported to the European Liver Transplant Registry. In view of the difficult differential diagnosis between HAS and hemangioendothelioma (HE), the study was deliberately restricted to the period 1986 to 2004 to allow comparison of clinical and biochemical behavior of HAS and HE liver recipients transplanted during the same time period. Results. Clinical signs, symptoms, and biochemical parameters differed significantly. Pre-LT diagnosis of HAS was made in only 5 of 16 (31%) biopsied patients. HE (7 patients) and hepatocellular cancer (2 patients) were confounding diagnoses leading to LT. Extrahepatic disease was present at time of LT in 4 (19%) patients. Giant invalidating tumor (5 HAS, 1 with Budd-Chiari syndrome [BCS], and 10 supposed epithelioid hemangioendothelioma, 1 with BCS), acute BCS of unknown origin (2 patients), chronic liver failure (4 patients), and solitary hepatocellular cancer (1 patient) were the main indications for LT. Overall survival was 7.2±2.6 months; no patient survived after 23 months. Recurrence was diagnosed after 5.0±2.6 months. Seventeen (77.2%) patients died of tumor recurrence, and the remaining 5 patients died of early infections. Conclusions. HAS is an absolute contraindication to LT due to the poor outcome. When dealing with the difficult differential diagnosis between HAS and HE, futile LT can be avoided by taking into consideration their distinct clinical and biochemical behaviors as well as a 6-month wait-list observation period. This time period enables the evaluation of HAS disease progression without compromising prognosis of HE patients, thereby allowing to avoid organ wastage. © 2013 Lippincott Williams & Wilkins.

Background: Confidence in intraoperative neurophysiologic monitoring (IONM) data can allow scoliosis surgeons to proceed with surgery even after a monitoring alert, assuming the recovery of signals. We sought to determine the outcomes of surgical treatment of adolescent idiopathic scoliosis (AIS) after a notable IONM alert. Methods: We identified 676 patients who underwent arthrodesis with use of IONM for the treatment of AIS. The patients were divided into 2 cohorts: those who experienced a lower-extremity IONM alert and those who did not. An alert was defined as a notable change in IONM data, specifically, a ≥50% drop in somatosensory evoked potentials (SSEPs) and/or in transcranial motor evoked potentials (tcMEPs). Results: Of the 676 patients, 36 (5.3%) experienced IONM alerts. Those patients had a larger preoperative major Cobb angle (mean of 61° ± 13° compared with 55° ± 12° for the no-alert group; p < 0.01), a greater number of levels fused (mean of 12 ± 2 compared with 11 ± 2; p < 0.01), a longer operative duration (mean of 357 ± 157 minutes compared with 298 ± 117 minutes; p < 0.01), a higher estimated blood loss (1,857 ± 1,323 mL compared with 999 ± 796 mL; p < 0.01), and a greater volume of autologous blood transfused (mean of 527 ± 525 mL compared with 268 ± 327 mL; p < 0.01). Among patients who experienced an alert and had a completed operation (34 of 36 patients), mean postoperative radiographic measurements were similar to those of the no-alert group in terms of the percentage of correction of the major Cobb angle (alert, 66% ± 13%; no alert, 64% ± 19%; p = 0.53) and of rib prominence (alert, 49% ± 36%; no alert, 47% ± 46%; p = 0.83) and measurement of thoracic kyphosis (alert, 23° ± 10°; no alert, 22° ± 2°; p = 0.58). The Scoliosis Research Society (SRS)-22 outcome scores were also similar between the 2 cohorts. Conclusions: Notable IONM changes occurred in 5.3% of the patients who underwent arthrodesis for AIS. Those patients had larger preoperative deformity, a longer operative duration, a greater number of levels fused, a higher estimated blood loss, and a greater volume of autologous blood transfused. Return of IONM data guided the surgeon to safely complete the procedure in 34 of 36 patients, with correction similar to that of patients who did not experience an alert. Level of Evidence: Therapeutic Level III. See Instructions for Authors for a complete description of levels of evidence.

The outcome of tissue engineered organ transplants depends on the capacity of the biomaterial to promote a pro-healing response once implanted in vivo. Multiple studies, including ours, have demonstrated the possibility of using the extracellular matrix (ECM) of animal organs as platform for tissue engineering and more recently, discarded human organs have also been proposed as scaffold source. In contrast to artificial biomaterials, natural ECM has the advantage of undergoing continuous remodeling which allows adaptation to diverse conditions. It is known that natural matrices present diverse immune properties when compared to artificial biomaterials. However, how these properties compare between diseased and healthy ECM and artificial scaffolds has not yet been defined. To answer this question, we used decellularized renal ECM derived from WT mice and from mice affected by Alport Syndrome at different time-points of disease progression as a model of renal failure with extensive fibrosis. We characterized the morphology and composition of these ECMs and compared their in vitro effects on macrophage activation with that of synthetic scaffolds commonly used in the clinic (collagen type I and poly-L-(lactic) acid, PLLA). We showed that ECM derived from Alport kidneys differed in fibrous protein deposition and cytokine content when compared to ECM derived from WT kidneys. Yet, both WT and Alport renal ECM induced macrophage differentiation mainly towards a reparative (M2) phenotype, while artificial biomaterials towards an inflammatory (M1) phenotype. Anti-inflammatory properties of natural ECMs were lost when homogenized, hence three-dimensional structure of ECM seems crucial for generating an anti-inflammatory response. Together, these data support the notion that natural ECM, even if derived from diseased kidneys promote a M2 protolerogenic macrophage polarization, thus providing novel insights on the applicability of ECM obtained from discarded organs as ideal scaffold for tissue engineering.

Retrospective analysis of the prospectively collected data.To investigate the relationship between the axial rotation of the unfused lumbar spine and the parameters of the instrumented thoracic spine at varying time points after selective thoracic fusion (STF) in Lenke 1B and 1C adolescent idiopathic scoliosis (AIS).The impact of STF on the spontaneous lumbar curve correction in AIS has been studied mainly in the frontal planes. The relationship between the spontaneous transverse plane correction of the lumbar spine and the parameters of the fused thoracic spine is not well documented.Twenty-one Lenke 1B and 1C patients who had received STF with minimum two years' follow-up were selected. Thoracic and lumbar Cobb angles, kyphosis, lordosis, and thoracic and lumbar apical vertebrae rotations were measured at preoperative, first-erect, six-month, one-year, and two-year follow-ups. The association between the lumbar apical vertebral rotation and other thoracic and lumbar variables at different time points were determined using regression analysis. The variables significantly predicting the lumbar axial rotation correction at two years were determined from the preceding follow-up visits.Kyphosis, thoracic Cobb, thoracic apical vertebral rotation, and lumbar Cobb were significantly different between the preoperative and all the postoperative follow-ups (p.05). At the two-year follow-up, a decrease in thoracic rotation and lumbar Cobb and a higher residual thoracic Cobb were associated with an improved spontaneous lumbar rotation (RSpontaneous lumbar curve rotation correction correlated to the fused and unfused spinal parameters in the three anatomic planes. The relationship between thoracic and lumbar rotation persist up to two years after STF. Thoracic derotation is an important factor determining the lumbar rotation correction at two years after STF.

We report herein the 10-year outcome of the Tor Vergata weaning off immunosuppression protocol in hepatitis C virus (HCV) liver transplant patients. Thirty-four patients who had received a liver graft for HCV-related cirrhosis were enrolled in a prospective study in which they were progressively weaned off immunosuppression. The primary endpoints were feasibility and safety of the weaning; the second aim was to assess fibrosis progression. At the 10-year follow-up, of the eight original tolerant patients, six remained IS-free. Of the 26 individuals who could not be weaned, 22 were alive. When the baseline biopsies were compared with the 10-year biopsies, the tolerant group showed no differences in staging, whereas the nontolerant group showed a significant increase in staging. The fibrosis progression rates calculated for the tolerant and the nontolerant groups were -0.06 ± 0.12 and 0.1 ± 0.2, respectively (P = 0.04). Furthermore, with the last taken biopsies, nine nontolerant patients were showing frank cirrhosis versus no cirrhosis among the tolerant patients. After a 10-year follow-up of a Tor Vergata weaning protocol, 6/34 patients completed follow-up without reinstitution of immunosuppression and this appeared beneficial regarding a reduction in fibrosis progression.

Item does not contain fulltext We report here on a European cohort of 27 kidney transplant recipients displaying operational tolerance, compared to two cohorts of matched kidney transplant recipients under immunosuppression and patients who stopped immunosuppressive drugs and presented with rejection. We report that a lower proportion of operationally tolerant patients received induction therapy (52% without induction therapy vs. 78.3%[p = 0.0455] and 96.7%[p = 0.0001], respectively), a difference likely due to the higher proportion (18.5%) of HLA matched recipients in the tolerant cohort. These patients were also significantly older at the time of transplantation (p = 0.0211) and immunosuppression withdrawal (p = 0.0002) than recipients who rejected their graft after weaning. Finally, these patients were at lower risk of infectious disease. Among the 27 patients defined as operationally tolerant at the time of inclusion, 19 still display stable graft function (mean 9 +/- 4 years after transplantation) whereas 30% presented slow deterioration of graft function. Six of these patients tested positive for pre-graft anti-HLA antibodies. Biopsy histology studies revealed an active immunologically driven mechanism for half of them, associated with DSA in the absence of C4d. This study suggests that operational tolerance can persist as a robust phenomenon, although eventual graft loss does occur in some patients, particularly in the setting of donor-specific alloantibody.

Background Nodular regenerative hyperplasia (NRH) is the leading cause of non-cirrhotic portal hypertension in Western countries. Although some patients are successfully managed medically or with shunting procedures, others require liver transplantation. The aim of this review was to assess the overall results obtained with liver transplantation and to better define its role in this setting. Methods Systematic review of all published studies on liver transplantation for NRH without language restrictions, in Medline, Embase and Cochrane Library databases through March 2010. Results 17 studies including a total of 73 patients were identified; 47 (64.3%) were excluded due to lacking inclusion criteria or clinical data and 26 (35.7%) were analysed. Before liver transplantation, the most frequent clinical presentation was gastroesophageal bleeding (65.3%) followed by ascites (61.5%), hepatic encephalopathy (30.7%) and liver failure (11.5%). The mean follow-up reported after liver transplantation was 30.6 ± 27.6 months and patient and graft survival rate was 78.3%. Only one case reported a NRH recurrence 7 years after liver transplantation (LT). Conclusions Although there are no hard data supporting the role of liver transplantation in symptomatic NRH, onset of severe portal hypertension in this setting may represent a valid indication.

Hepatitis C virus (HCV) recurrence after orthotopic liver transplantation (LT) is universal. We designed a retrospective case-control study to evaluate the effect of mycophenolate mofetil (MMF) monotherapy in patients with recurrent hepatitis C. Fifteen patients with histologically proven hepatitis C recurrence after LT were switched from calcineurin inhibitors (CNIs) to MMF monotherapy because of impairment of kidney function and/or metabolic side effects, and treated for 48 months (MMF group). Fifteen well-matched LT recipients who continued to receive CNIs therapy over the same period served as control group. Demographics, clinical data, time after LT, and baseline liver biopsies were similar in the two groups. There was no worsening of hepatic fibrosis during the study in the MMF group [2.6 ± 1.5 (baseline) Ishak Units vs. 2.7 ± 1.8 (after 48 months of MMF treatment), P = 0.6]. In contrast, a significant increase in the fibrosis score [2 ± 1.1 (baseline) vs. 3.2 ± 1.7 (after 48 months of CNI treatment), P = 0.0002] was observed in the control group. The yearly fibrosis progression rate was of 0.05 ± 0.44 in the MMF group and 0.33 ± 0.24 in the CNI group (P = 0.04). MMF monotherapy is associated with a favourable effect on hepatic fibrosis progression in HCV liver transplant recipients.

This review will provide evidence that selected patients with type 2 diabetes mellitus (T2DM) may benefit from vascularized pancreas transplantation (PTX).Initial experience with simultaneous pancreas-kidney transplantation (SPKT) in patients with T2DM and end-stage renal disease (ESRD) suggested that augmentation of endogenous insulin production by PTX in patients with C-peptide-positive, insulin-requiring diabetes resulted in insulin independence, improved glucose counter-regulation, and enhanced quality of life. A number of single-center retrospective studies have documented equivalent outcomes in patients with either type 1 diabetes mellitus (T1DM) or T2DM undergoing predominantly SPKT, although clearly a selection bias exists for patients in the latter category. Selection criteria for SPKT in T2DM include patients less than 55-60 years of age with a BMI less than 30-32 kg/m², insulin-requiring for a minimum of 5 years with a total daily insulin requirement less than 1 u/kg/day, a fasting C-peptide level less than 10 ng/ml, absence of severe vascular disease or tobacco abuse, adequate cardiac function, and presence of 'complicated' diabetes. Data from the International Pancreas Transplant Registry show that up to 7% of SPKT recipients are classified as having T2DM and that outcomes in these patients are comparable to those undergoing SPKT and classified as having T1DM.Consequently, characterization of the 'type' of diabetes may be irrelevant and insulin-requiring diabetic patients with ESRD should be evaluated for PTX based exclusively on their predicted ability to tolerate the surgical procedure and requisite immunosuppression as well as comply with a stringent posttransplant follow-up regimen.

In solid organ transplantation, the achievement of an immunosuppression (IS)-free state [also referred to as clinical operational tolerance (COT)] represents the ultimate goal. Although COT is feasible and safe in selected cases after liver transplantation, it is an exceptional finding after other types of solid organ transplantation. In the field of renal transplantation (RT), approximately 100 cases of COT have been reported to date, mainly in patients who were not compliant with their immunosuppressive regimens or in individuals who had previously received a bone marrow transplant for hematological disorders. On the basis of promising results obtained in animal models, several tolerogenic protocols have been attempted in humans, but most have failed to achieve robust and stable COT after RT. Molecule-based regimens have been largely ineffective, whereas cell-based regimens have provided some encouraging results. In these latter regimens, apart from standard IS, patients usually receive perioperative infusion of donor bone marrow–derived stem cells, which are able to interact with the immune cells of the host and mitigate their response to engraftment. Unfortunately, most renal transplant patients who developed acute rejection—occurring either during the weaning protocol or after complete withdrawal of IS—eventually lost their grafts. Currently, the immune monitoring necessary for predicting the presence and persistence of donor-specific unresponsiveness is not available. Overall, the present review will provide a conceptual framework for COT and conclude that stable and robust COT after RT remains an elusive goal and that the different strategies attempted to date are not yet reproducibly safe or effective.

INTRODUCTION Deceased donor (DD) kidneys exhibiting severe atherosclerosis involving the renal artery (RA) may represent a contraindication to kidney transplantation (KT). METHODS Eversion endarterectomy (EE) was performed as a salvage procedure to permit KT. RESULTS We identified 17 cases (1.2% of all DD KTs during the study period) involving EE of the DD RA. Thirteen (76.5%) kidneys were imported, and mean Kidney Donor Profile Index (KDPI) was 81%. Mean DD age was 59 years, mean RA plaque length was 1.7 cm, and mean glomerulosclerosis on biopsy was 10%. Mean recipient age was 64 years, and dialysis vintage was 32 months. With a mean follow-up of 36 months, actual patient and graft survival rates were both 76.5%. One patient died early without a technical problem. Of the remaining 16 patients, 2-year patient and graft survival rates were both 100%. There were no early or late vascular complications. The incidence of delayed graft function was 35%. Mean serum creatinine and GFR levels in patients with functioning grafts at latest follow-up were 1.8 mg/dL and 40 mL/min, respectively. CONCLUSIONS EE appears to be a safe and under-utilized procedure that may prevent discard of marginal donor kidneys and is associated with acceptable short-term outcomes.

To determine the impact of prolonged cold ischemia time (CIT) on the outcome of acute kidney injury (AKI) renal grafts, we therefore performed a single-center retrospective analysis in adult patients receiving kidney transplantation (KT) from AKI donors. Outcomes were stratified according to duration of CIT. A total of 118 patients receiving AKI grafts were enrolled. Based on CIT, patients were stratified as follows: (i)20 hours, 27 patients; (ii) 20-30 hours, 52 patients; (iii) 30-40 hours, 30 patients; (iv) ≥40 hours, nine patients. The overall incidence of delayed graft function DGF was 41.5%. According to increasing CIT category, DGF rates were 30%, 42%, 40%, and 78%, respectively (P = .03). With a mean follow-up of 48 months, overall patient and graft survival rates were 91% and 81%. Death-censored graft survival (DCGS) rates were 84% and 88% for patients with and without DGF (P = NS). DCGS rates were 92% in patients with CIT20 hours compared to 85% with CIT20 hours (P = NS). In the nine patients with CIT40 hours, the 4-year DCGS rate was 100%. We conclude that prolonged CIT in AKI grafts may not adversely influence outcomes and so discard of AKI kidneys because of projected long CIT is not warranted when donors are wisely triaged.

At the Tor Vergata University of Rome, ab initio calcineurin inhibitor-based monotherapy immunosuppression (IS) is the standard of treatment after liver transplantation (LT). As the net state of IS determines the onset of Pneumocystis jirovecii pneumonia (PCP), we hypothesized that, in the presence of weak impairment of the immune function, as determined by the above-mentioned IS, the host is not overexposed to the risk for PCP and consequently the specific anti-PCP prophylaxis is unnecessary. In a single-cohort descriptive study, we retrospectively investigated the incidence of PCP in 203 LT patients who did not receive anti-PCP prophylaxis because they were under monotherapy IS. The primary endpoint of the study was the incidence of PCP during the first 12 months following LT; secondary endpoints were the incidence of acute rejection requiring additional IS and of CMV infection. No cases of PCP were recorded. The incidence of CMV and acute rejection was 3.9% and 0.9%, respectively. Our data suggest that monotherapy IS after LT may nullify the risk for PCP even in the absence of any specific prophylaxis.

Pseudomonas aeruginosa (PA) infections occurring after renal transplantation (RT) represent a potentially life-threatening complication. We present 2 cases of early death following RT in which PA was transmitted, possibly from the donor to the recipients, despite preoperative cultures that were negative. The donor had developed PA-related bilateral pneumonia while in the intensive care unit. However, after appropriate antibiotic therapy, no signs of infection were present at the time of organ retrieval and cultures were negative. Both recipients received a renal graft from the same donor and developed multi-drug resistant (MDR)-PA infections with bacterial phenotypes and resistances similar to the donor. The first recipient died 9 days after RT from rupture of a false aneurysm of the external iliac artery, caused by a fully thickened PA-related arteritis. The second recipient died postoperatively on day 10 after rupture of an aneurysm in the right vertebral artery. Our experience shows that MDR-PA infection early after RT may be a catastrophic event. Specific anti-PA antibiotic therapy in RT patients during the perioperative period is recommended in the case of PA infection in the donor, even after apparent successful therapy with negative cultures.

Although late ureteral obstruction represents the most frequent urologic complication after renal transplantation, its etiology remains poorly understood. Benign prostatic hyperplasia (BPH) is the most common cause of urinary tract obstruction in the adult male population, but information regarding BPH epidemiology and its impact on clinical outcomes are lacking. We herein have described a case of ureteral herniation into the scrotum, secondary to concomitant upper and lower urinary tract obstruction: namely, BPH and ureterovesical junction stenosis causing massive urine retention and acute renal failure. The simultaneous presence of the 2 lesions rendered the diagnosis difficult. In addition, urine outflow responsible for bladder outlet obstruction resumed after transurethral resection of the prostate (TURP). The hydroureteronephrosis, which persisted after the TURP resolved only after positioning a double J stent, but renal function did not normalize. Attention must be paid to BPH in the differential diagnosis of urinary tract obstruction. Stenosis of the ureterovesical junction may occur very late after transplantation.

Ninety percent of all carcinoid tumors develop in the gastrointestinal tract. Although the liver is a usual site for metastases, primary hepatic carcinoid tumors (PHCTs) are extremely rare. The diagnosis is based on histopathologic characteristics and on exclusion of a nonhepatic primary tumor. While liver transplantation (OLT) is a well-established surgical treatment in selected cases of unresectable metastatic carcinoid tumor, its use in PHCT has not been widely described. We report the case of a 50-year-old woman with unresectable PHCT treated with OLT. After 64 months, disease recurred in the liver and mesentery. Laparotomy with multiple radiofrequency ablations of liver lesions and resection of peritoneal deposits was performed; however, in the postoperative period, a fatal myocardial infarct occurred. Our case is the fourth one reported in literature. It confirms long-term survival after OLT in patients with unresectable PHTCs.

An alternative technique for urinary tract (UT) reconstruction is described in a renal transplant recipient who developed a severe stenosis of the graft ureter. This approach entails the retroperitoneoscopic preparation of the native ureter contralateral to the graft, followed by an open reconstruction of the UT. The ureter was dissected along its entire length to the level of the iliac vessels, with its associated mesentery still attached in order to preserve the vascular supply. The corresponding native kidney contralateral to the graft was endoscopically removed. A longitudinal sub-umbilical incision allowed the excision of the stenotic tract and the reconstruction of the UT by means of a manual end-to-end anastomosis between the new ureter and the graft pelvis. No post-operative complications occurred and renal function immediately resumed. The approach described represents an alternative solution for the surgical management of severe ureteric graft stenosis. We believe that the magnification of the anatomy granted by the endoscope during the dissection of the ureter and neighboring structures provides the gentle handling of the tissues and the remote dissection away from the ureter with the highest precision.

We report a noteworthy case of Eubacterium plautii infection after kidney transplantation. Our 33-yr-old transplant recipient received standard care; his post-transplant course was uneventful. However, on day 44 he underwent an emergency laparotomy for perforation of the ileum. He was initially treated with ceftazidime, fluconazole and metronidazole, but his fever persisted, so he was switched to meropenem and vancocin. We could not find any cause for his infection. On day 70, his temperature normalized. On day 75, he developed severe leukopenia (280 cell/mL). His cytomegalovirus-DNA test result was negative, so all immunosuppressants, except for prednisone, were stopped; instead, antibiotic prophylaxis was started, using caspofungin, trimethoprim-sulfamethoxazole and ciprofloxacin. On day 83, he underwent percutaneous drainage of massive left pleural effusion. We repeatedly cultured the pleural liquid, but it was not till three wk later that we were finally able to identify the causative organism. We hypothesize that the microorganism - which normally resides on the surface of the intestinal lumen - entered the bloodstream via bacterial translocation, eventually colonizing the pleurae. This translocation was favored by our patient poor clinical condition, his immunosuppressive treatment and his heavy antibiotherapy. Our experience highlights the need for wiser use of antibiotics in transplant recipients.

BACKGROUND: Hepatic epitheloid hemangioendothelioma (HEHE) is a rare low-grade vascular tumor. Its treatment algorithm is still unclear mainly due to a lack of larger clinical experiences with detailed long-term follow-up. MATERIAL AND METHODS: Fifty-nine patients, reported to the European Liver Transplant Registry, were analyzed to define the role of liver transplantation (LT) in the treatment of this disease. Eleven (19%) patients were asymptomatic. Eighteen (30.5%) patients had pre-LT surgical [hepatic (7 patients) and extrahepatic (3 patients)] and/or systemic or locoregional (10 patients) medical therapy. Ten (16.9%) patients had extrahepatic disease localization before or at the time of LT. Follow-up was complete for all patients with a median of 92.5 (range, 7-369) from moment of diagnosis and a median of 78.5 (range, 1-245) from the moment of LT. RESULTS: HEHE was bilobar in 96% of patients; 86% of patients had more than 15 nodules in the liver specimen. Early ( 3 months) post-LT mortality was 1.7% (1 patient) and 22% (14 patients). Fourteen (23.7%) patients developed disease recurrence after a median time of 49 months (range, 6-98). Nine (15.3%) patients died of recurrent disease and 5 are surviving with recurrent disease. One-, 5-, and 10- year patient survival rates from moment of transplantation for the whole series are 93%, 83%, 72%. Pre-LT tumor treatment (n = 18) (89%, 89%, and 68% 1-, 5-, and 10-year survival rates from moment of LT vs. 95%, 80%, and 73% in case of absence of pre-LT treatment), lymph node (LN) invasion (n = 18) (96%, 81%, and 71% 1-, 5-, and 10-year survival rates vs. 83%, 78%, and 67% in node negative patients) and extrahepatic disease localization (n = 10) (90%, 80%, and 80% 1-, 5-, and 10-year survival rates vs. 94%, 83%, and 70% in case of absence of extrahepatic disease) did not significantly influence patient survival whereas microvascular (n = 24) (96%, 75%, 52% 1-, 5-, and 10-year survival vs. 96%, 92%, 85% in case of absence of microvascular invasion) and combined micro- and macrovascular invasion (n = 28) (90%, 72%, and 54% 1-,5-, and 10-year survival vs. 96%, 92%, and 85% in case of absence of vascular invasion, P = 0.03) did. Disease-free survival rates at 1, 5, and 10 years post-LT are 90%, 82%, and 64%. Disease-free survival is not significantly influenced by pre-LT treatment, LN status, extrahepatic disease localization, and vascular invasion. CONCLUSIONS: The results of the largest reported transplant series in the treatment of HEHE are excellent. Preexisting extrahepatic disease localization as well as LN involvement are not contraindications to LT. Microvascular or combined macro-microvascular invasion significantly influence survival after LT. LT therefore should be offered as a valid therapy earlier in the disease course of these, frequently young, patients. Recurrent (allograft) disease should be treated aggressively as good long-term survivals can be obtained. Long-term prospective follow-up multicenter studies as well as the evaluation of antiangiogenic drugs are necessary to further optimize the treatment of this rare vascular hepatic disorder.

This article is based on a review of the recent literature and the experience gathered by the European Liver Transplant Registry (ELTR) with the aim to summarize the current evidence for OLT for the treatment of vascular and other rare liver tumors.

Kidney transplantation (KT), as a modality of renal replacement therapy (RRT), has been shown to be both economically and functionally superior to dialysis for the treatment of end-stage renal disease (ESRD). Progress in KT is limited by two major barriers: a) a chronic and burgeoning shortage of transplantable organs and b) the need for chronic immunosuppression following transplantation. Although ground-breaking advances in transplant immunology have improved patient survival and graft durability, a new pathway of innovation is needed in order to overcome current obstacles. Regenerative medicine (RM) holds the potential to shift the paradigm in RRT, through organ bioengineering. Manufactured organs represent a potentially inexhaustible source of transplantable grafts that would bypass the need for immunosuppressive drugs by using autologous cells to repopulate extracellular matrix (ECM) scaffolds. This overview discusses the current status of renal transplantation while reviewing the most promising innovations in RM therapy as applied to RRT.

BACKGROUND Serial casting for early-onset scoliosis has been shown to improve curve deformity. Our goal was to define clinical and radiographic features that determine response to treatment. METHODS We retrospectively reviewed patients with idiopathic infantile scoliosis with a minimum of 2-year follow-up. Inclusion criteria were: progressive idiopathic infantile scoliosis and initial casting before 6 years of age. Two groups were analyzed and compared: group 1 (≥10-degree improvement in Cobb angle from baseline) and group 2 (no improvement). RESULTS Twenty-one patients with an average Cobb angle of 48 degrees (range, 24 to 72 degrees) underwent initial casting at an average age of 2.1 years (range, 0.7 to 5.4 y). Average follow-up was 3.5 years (range, 2 to 6.9 y). Sex, age at initial casting, magnitude of spinal deformity, and curve flexibility (defined as change in Cobb angle from pretreatment to first in-cast radiograph) were not significantly different between groups (P>0.05). Group 1 had a significantly higher body mass index (BMI) than group 2 at the onset of treatment (17.6 vs. 14.8, P

Background Kidney recipients maintaining a prolonged allograft survival in the absence of immunosuppressive drugs and without evidence of rejection are supposed to be exceptional. The ERA-EDTA-DESCARTES working group together with Nantes University launched a European-wide survey to identify new patients, describe them and estimate their frequency for the first time. Methods Seventeen coordinators distributed a questionnaire in 256 transplant centres and 28 countries in order to report as many operationally tolerant patients (TOL; defined as having a serum creatinine