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BACKGROUND & AIMS: Machine perfusion is a novel method intended to optimize livers before transplantation. However, its effect on morbidity within a 1-year period after transplantation has remained unclear. METHODS: In this multicenter controlled trial, we randomly assigned livers donated after brain death (DBD) for liver transplantation (LT). Livers were either conventionally cold stored (control group), or cold stored and subsequently treated by 1-2 h hypothermic oxygenated perfusion (HOPE) before implantation (HOPE group). The primary endpoint was the occurrence of at least one post-transplant complication per patient, graded by the Clavien score of ≥III, within 1-year after LT. The comprehensive complication index (CCI), laboratory parameters, as well as duration of hospital and intensive care unit stay, graft survival, patient survival, and biliary complications served as secondary endpoints. RESULTS: Between April 2015 and August 2019, we randomized 177 livers, resulting in 170 liver transplantations (85 in the HOPE group and 85 in the control group). The number of patients with at least one Clavien ≥III complication was 46/85 (54.1%) in the control group and 44/85 (51.8%) in the HOPE group (odds ratio 0.91; 95% CI 0.50-1.66; p = 0.76). Secondary endpoints were also not significantly different between groups. A post hoc analysis revealed that liver-related Clavien ≥IIIb complications occurred less frequently in the HOPE group compared to the control group (risk ratio 0.26; 95% CI 0.07-0.77; p = 0.027). Likewise, graft failure due to liver-related complications did not occur in the HOPE group, but occurred in 7% (6 of 85) of the control group (log-rank test, p = 0.004, Gray test, p = 0.015). CONCLUSIONS: HOPE after cold storage of DBD livers resulted in similar proportions of patients with at least one Clavien ≥III complication compared to controls. Exploratory findings suggest that HOPE decreases the risk of severe liver graft-related events. IMPACT AND IMPLICATIONS: This randomized controlled phase III trial is the first to investigate the impact of hypothermic oxygenated perfusion (HOPE) on cumulative complications within a 12-month period after liver transplantation. Compared to conventional cold storage, HOPE did not have a significant effect on the number of patients with at least one Clavien ≥III complication. However, we believe that HOPE may have a beneficial effect on the quantity of complications per patient, based on its application leading to fewer severe liver graft-related complications, and to a lower risk of liver-related graft loss. The HOPE approach can be applied easily after organ transport during recipient hepatectomy. This appears fundamental for wide acceptance since concurring perfusion technologies need either perfusion at donor sites or continuous perfusion during organ transport, which are much costlier and more laborious. We conclude therefore that the post hoc findings of this trial should be further validated in future studies. ispartof: JOURNAL OF HEPATOLOGY vol:78 issue:4 pages:783-793 ispartof: location:Netherlands status: published

Background and Aims: Identifying international differences in utilization and outcomes of liver transplantation (LT) after donation after circulatory death (DCD) donation provides a unique opportunity for benchmarking and population-level insight. Methods: Adult (≥18 years) LT data between 2008 and 2018 from the UK and US were used to assess mortality and graft failure after DCD LT. We used time-dependent Cox-regression methods to estimate hazard ratios (HR) for risk-adjusted short-term (0–90 days) and longer-term (90 days–5 years) outcomes. Results: One-thousand five-hundred-and-sixty LT receipts from the UK and 3426 from the US were included. Over the study period, the use of DCD livers increased from 15.7% to 23.9% in the UK compared to 5.1% to 7.6% in the US. In the UK, DCD donors were older (UK:51 vs. US:33 years) with longer cold ischaemia time (UK: 437 vs. US: 333 min). Recipients in the US had higher Model for End-stage Liver Disease (MELD) scores, higher body mass index, higher proportions of ascites, encephalopathy, diabetes and previous abdominal surgeries. No difference in the risk-adjusted short-term mortality or graft failure was observed between the countries. In the longer-term (90 days–5 years), the UK had lower mortality and graft failure (adj.mortality HR:UK: 0.63 (95% CI: 0.49–0.80); graft failure HR: UK: 0.72, 95% CI: 0.58–0.91). The cumulative incidence of retransplantation was higher in the UK (5 years: UK: 11.9% vs. 4.6%; p

BACKGROUND AND AIM Liver graft utilization rates are a hot topic due to the worldwide organ shortage and an increasing number of transplant candidates on waiting lists. Liver perfusion techniques have been introduced in several countries, and may help to increase the organ supply, as they potentially allow the assessment of livers before use. METHODS Liver offers were counted from donation after circulatory death (DCD) donors (Maastricht-type-III) arising during the past decade in eight countries, including Belgium, France, Italy, the Netherlands, Spain, Switzerland, UK, and US. Initial DCD-type-III liver offers were correlated with accepted, recovered and implanted livers. RESULTS A total number of 34`269 DCD livers were offered, resulting in 9`780 liver transplants (28.5%). The discard rates were highest in UK and US, ranging between 70 and 80%. In contrast, much lower DCD liver discard rates, e.g., between 30-40%, were found in Belgium, France, Italy, Spain and Switzerland. In addition, large differences were recognized in the use of various machine perfusion techniques, and in terms of risk factors in the cohorts of implanted livers. For example, the median donor age and functional donor warm ischemia were highest in Italy, e.g., >40minutes, followed by Switzerland, France, and the Netherlands. Importantly, such varying risk profiles of accepted DCD livers between countries did not translate into large differences in five-year graft survival rates, which ranged between 60-82% in this analysis. CONCLUSIONS We highlight a significant number of discarded and consequently unused DCD liver offers. Countries with more routine use of in- and ex-situ machine perfusion strategies showed better DCD utilization rates without compromised outcome. IMPACT AND IMPLICATIONS A significant number of Maastricht type III DCD livers are discarded across Europe and North America today. The overall utilization rate among eight Western countries is 28.5%, but varies significantly between 18.9% and 74.2%. For example, the median DCD III liver utilization in five countries, e.g., Belgium, France, Italy, Switzerland, and Spain is 65%, in contrast to 24% in the Netherlands, UK and US. Despite this, and despite different rules and strategies for organ acceptance and preservation, the one and five-year graft survival remains currently relatively comparable among all participating countries. Factors which impact on DCD liver acceptance rates include the national pre-selections of donors, before the offer is made, as well as cutoffs for key risk factors, including donor age and donor warm ischemia time. In addition, a highly varying experience with modern machine perfusion technology is noticed. In situ and ex situ liver perfusion concepts, and assessment tools for type III DCD livers before transplantation may be one key part for the observed differences in better DCD III utilization.

Background As modern medicine is advancing, younger, small, and more complex children are becoming multi-organ transplant candidates. This brings up new challenges in all aspects of their care. Methods We describe the first report of a small child receiving a simultaneous liver and kidney transplant and abdominal rectus sheath fascia transplant on the background of Williams syndrome and methylmalonic acidaemia. At the time of transplantation, the child was 3 years old, weighed 14.0 kg, had chronic kidney disease stage V, and had not yet started any other form of kidney replacement therapy. Results There were many anaesthetic, medical, metabolic, and surgical challenges to consider in this case. A long general anaesthetic time increased the risk of cardiac complications and metabolic decompensation. Additionally, the small size of the patient and the organ size mis-match meant that primary abdominal closure was not possible. The patient’s recovery was further complicated by sepsis, transient CNI toxicity, and de novo DSAs. Conclusions Through a multidisciplinary approach between 9 specialties in 4 hospitals across England and Wales, and detailed pre-operative planning, a good outcome was achieved for this child. An hour by hour management protocol was drafted to facilitate transplant and included five domains: 1. management at the time of organ offer; 2. before the admission; 3. at admission and before theatre time; 4. intra-operative management; and 5. post-operative management in the first 24 h. Importantly, gaining a clear and in depth understanding of the metabolic state of the patient pre- and peri-operatively was crucial in avoiding metabolic decompensation. Furthermore, an abdominal rectus sheath fascia transplant was required to achieve abdominal closure, which to our knowledge, had never been done before for this indication. Using our experience of this complex case, as well as our experience in transplanting other children with MMA, and through a literature review, we propose a new perioperative management pathway for this complex cohort of transplant recipients.

Background: Biliary atresia (BA) is the most common indicator for liver transplant (LT) in children, however, approximately 22% will reach adulthood with their native liver, and of these, half will require transplantation later in life. The aim of this study was to analyse the surgical challenges and outcomes of patients with BA undergoing LT in adulthood. Methods: Patients with BA requiring LT at the age of 16 or older in our unit between 1989 and 2020 were included. Pretransplant, perioperative variables and outcomes were analysed. Pretransplant imaging was reviewed to assess liver appearance, spontaneous visceral portosystemic shunting (SPSS), splenomegaly, splenic artery (SA) size, and aneurysms. Results: Thirty-four patients who underwent LT for BA fulfilled the inclusion criteria, at a median age of 24 years. The main indicators for LT were synthetic failure and recurrent cholangitis. In total, 57.6% had significant enlargement of the SA, 21% had multiple SA aneurysm, and SPSS was present in 72.7% of the patients. Graft and patient survival at 1, 5, and 10 years was 97.1%, 91.2%, 91.2% and 100%, 94%, 94%, respectively Conclusions: Good outcomes after LT for BA in young patients can be achieved with careful donor selection and surgery to minimise the risk of complications. Identification of anatomical variants and shunting are helpful in guiding attitude at the time of transplant.

Liver transplantation (LT) for small infants remains challenging because of the demands related to graft selection, surgical technique, and perioperative management. The aim of this study was to evaluate the short‐term and longterm outcomes of LT regarding vascular/biliary complications, renal function, growth, and patient/graft survival in infants ≤3 months compared with those of an age between >3 and 6 months at a single transplant center. A total of 64 infants ≤6 months underwent LT and were divided into 2 groups according to age at LT: those of age ≤3 months (range, 6‐118 days; XS group, n = 37) and those of age >3 to ≤6 months (range, 124‐179 days; S group, n = 27) between 1989 and 2014. Acute liver failure was the main indication for LT in the XS group (n = 31, 84%) versus S (n = 7, 26%). The overall incidence of hepatic artery thrombosis and portal vein thrombosis/stricture were 5.4% and 10.8% in the XS group and 7.4% and 11.1% in the S group, respectively (not significant). The overall incidence of biliary stricture and leakage were 5.4% and 2.7% in the XS group and 3.7% and 3.7% in the S group, respectively (not significant). There was no significant difference between the 2 groups in terms of renal function. No significant difference was found between the 2 groups for each year after LT in terms of height and weight z score. The 1‐, 5‐, and 10‐year patient survival rates were 70.3%, 70.3%, and 70.3% in the XS group compared with 92.6%, 88.9%, and 88.9% in the S group, respectively (not significant). In conclusion, LT for smaller infants has acceptable outcomes despite the challenges of surgical technique, including vascular reconstruction and graft preparation, and perioperative management.

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Donation after circulatory death (DCD) grafts are commonly used in liver transplantation. Attributable to the additional ischemic event during the donor warm ischemia time (DWIT), DCD grafts carry an increased risk for severe ischemia/reperfusion injury and postoperative complications, such as ischemic cholangiopathy. The actual ischemia during DWIT depends on the course of vital parameters after withdrawal of life support and varies widely between donors. The ischemic period (functional DWIT) starts when either Spo2 or blood pressure drop below a certain point and lasts until the start of cold perfusion during organ retrieval. Over the years, multiple definitions and thresholds of functional DWIT duration have been used. The International Liver Transplantation Society organized a Consensus Conference on DCD, Liver Preservation, and Machine Perfusion on January 31, 2020 in Venice, Italy. The aim of this conference was to reach consensus about various aspects of DCD liver transplantation in context of currently available evidence. Here we present the recommendations with regards to the definitions used for DWIT and functional DWIT, the importance of vital parameters after withdrawal of life support, and acceptable thresholds of duration of functional DWIT to proceed with liver transplantation. ispartof: TRANSPLANTATION vol:105 issue:6 pages:1156-1164 ispartof: location:United States status: published

The Risk Estimation of Tumor Recurrence After Transplant (RETREAT) score as a prognostic index for recurrence has been reported previously and has not been validated outside the USA. Our study has validated the score in a single center UK cohort of patients being transplanted for HCC.LT for HCC between 2008 and 2018 at our center were analyzed. Recurrence-free survival (RFS) was compared by the RETREAT score and validated using Net Reclassification Improvement (NRI) by comparing it to Milan criteria.346 adult HCC patients were transplanted of whom 313 were included. 28 (8.9%) had a recurrence. Summation of largest diameter and total number of viable tumors (HR = 1.19, p 0.001), micro-/macro-vascular invasion (HR = 3.74, p = 0.002) and AFP20 ng/ml (HR = 3.03, p = 0.005) were associated with recurrence on multivariate analysis. RFS decreased with increasing RETREAT score (log-rank p = 0.016). RETREAT performed better than Milan with significant NRI at 1- and 2-years post-transplant (0.43 (p = 0.004) and 0.38 (p = 0.03) respectively).LT outcomes using the revised UK criteria are equivalent to Milan criteria. Further, RETREAT score was validated as a prognostic index for the first time in a UK cohort and may assist risk stratification, selection for adjuvant therapies and guide surveillance.

Introduction Postoperative diaphragmatic hernia (DH) is a rare but potentially life-threatening complication following pediatric liver transplantation (LT). In the current literature, a total of 49 such hernias have been reported in 17 case series. We present eight additional cases, three of which reoccurred after surgical correction, and review the current literature with a focus on recurrence. Materials and Methods The study sample included children ( Results For the eight children with DH, the mean age at LT was 28.0 (5–132) months. All patients with a DH received left lateral segment split grafts except one, who received a full left lobe. The mean weight at time of LT was 11.8 (6.6–34) kg. Two patients had a primary abdominal muscle closure, and six had a temporary silastic mesh closure. All eight children presented with a right posterolateral DH. The small bowel was herniated in the majority of cases. Symptoms reported included nausea, vomiting, and respiratory distress. Two patients were asymptomatic, and discovery was incidental. All patients underwent prompt primary surgical repair. Three DH hernias (37.5%) recurred despite successful surgical correction. Conclusion DH following liver transplant with technical variant grafts may be underreported and is prone to recur despite surgical correction. A better understanding of the pathophysiology and more thorough reporting may help increase awareness. Early detection and prompt surgical management are the cornerstones of a successful outcome.

The increasing utilization of extended criteria donors (ECD) to overcome the demand of liver grafts and decrease the mortality on the waiting list for transplant, has led the transplant community to explore alternative preservation techniques to minimise the ischaemia reperfusion injury (IRI) associated to ECD, decrease the risk of complications and achieve similar outcomes. These new alternative preservation techniques have emerged in recent years, involving ex situ but also in situ machine perfusion, and it is predicted that it may become the standard of care in the near future. The advantage of these techniques is that they can preserve and provide oxygen to the donor liver, they can recondition and improve the donor organ quality, and in normothermic conditions they can provide a functional assessment and viability of the graft to help the surgeons in the decision making whether to utilize that liver. Other advantages are the potential to improve transplant logistics with prolonged preservation times and also the possibility of using therapeutic strategies during the perfusion to improve their quality or further minimise IRI. Current research is being undertaken using these different perfusion techniques alone or in combination to minimize the ischemic damaged suffered during procurement and cold preservation of the donor livers, to increase the donor pool and decrease the discard rates of ECD livers that could be safely transplanted.

Background We report our experience of treating anastomotic strictures using a novel type of fully covered metal stent (FCSEMS). This stent, known as the Kaffes Stent, is short-length with an antimigration waist and is easily removable due to long retrieval wires deployed within the duodenum. Methods Sixty-two patients underwent ERCP and Kaffes stent insertion for post-transplant anastomotic strictures following confirmation of a stricture on MRCP. These patients were retrospectively analysed for immediate and long-term stricture resolution, improvement in symptoms and liver function tests (LFTs), stricture recurrence and complication rates. Results Of the 56 patients who had their stent removed at the time of analysis, 54 (96%) had immediate stricture resolution and 42 continued to have long-term resolution (mean follow-up period was 548 days). Of the 16 patients with symptoms of biliary obstruction, 13 had resolution of their symptoms. Overall, there was a significant improvement in LFTs after stent removal compared to before stent insertion. Complication rates were 15% with only one patient requiring biliary reconstruction. Conclusions The Kaffes stent is effective and safe at resolving post liver transplant biliary anastomotic strictures.

Background: We report our experience of treating anastomotic strictures using a novel type of fully covered metal stent (FCSEMS). This stent, known as the Kaffes Stent, is short-length with an antimigration waist and easily removable due to long retrieval wires deployed within the duodenum. Methods: 62 patients who had this stent inserted were prospectively analysed. Results: 81% of patients had long-term resolution of their stricture with a significant improvement in liver function tests. Complication rates were 15% with one patient requiring biliary reconstruction. Conclusions: This type of FCSEMS is effective and safe at resolving anastomotic strictures.

Despite recent outcome improvement, liver transplantation from donation after circulatory death (DCD) donors remains a challenge. Multiple donor, graft and procurement factors not only contribute to the results after transplantation but also impact on the selection process and the decision to utilize or decline such livers, which potentially transmit a high risk for severe complications including primary graft non-function or ischemic cholangiopathy. Although the transplant community has gained significant experience in this field, the majority of risk factors is still inconsistently reported with various acceptance criteria and thresholds, when to accept a DCD donor liver, which also depends on national and centre guidelines and the surgeons’ experience. Throughout the past 10 years, we have developed an increasing awareness of the cumulative risk and how to best combine donor and recipient parameters, which encouraged the community to adapt the allocation process and to match certain DCD livers with presumed higher risk with healthier recipients, as, for example, with candidates with liver tumours. In this chapter, we highlight currently considered donor and graft risk factors and how they contribute to outcomes after transplantation. Additionally, we also describe the impact of donor surgery and current prediction models which may influence the DCD liver selection process and how we may expect new developments and preservation technology to impact on our decisions in the future.

In this review, we provide a state of the art of liver transplantation in children, as the procedure is now carried out for more than 30 years and most of our paediatric colleagues are managing these patients jointly with liver transplant centres. Our goal for this article is to enhance the understanding of the liver transplant process that a child and his family goes through while explaining the surgical advances and the associated complications that could happen in the immediate or long-term follow-up. We have deliberately introduced the theme that ‘liver transplant is a disease’ and ‘not a cure’, to emphasise the need for adherence with immunosuppression, a healthy lifestyle and lifelong medical follow-up.

In this paper we will describe anaesthetic management of solid organ and reconstructive transplantation (RT) patients. We will focus on similar underlying principles of reperfusion, ischaemic-reperfusion injury, preconditioning and extracorporeal donor organ preservation. Special concerns for anaesthetic management of these patients need to focus on pre-assessment, pre-operative optimisation, vascular access, fluid management, blood and products replacement, cardiovascular monitoring, use of inotropes and vasoconstrictors, maintaining electrolyte balance and regional anaesthesia. Despite the complexity and long duration of transplant procedures, fast-tracking to the surgical ward after transplantation is becoming more popular and its benefits are well recognised.

Primary abdominal wall closure after intestinal and multivisceral transplantation may not be possible because of loss of abdominal domain and/or graft size/abdominal cavity mismatch. Traditional closure techniques for the open abdomen may not be valid in these circumstances because of severe scarring of the abdominal wall from multiple previous surgeries in this particular group of patients. We present our initial experience with the use of non-vascularized abdominal rectus muscle fascia in two patients who underwent deceased donation and living-related combined liver and small bowel transplantation, respectively, and who could not be closed primarily. The donor fascia was attached to the recipient fascia in both patients. In either case, there was not enough skin cover for closure, the wound was left open, and a negative pressure dressing was applied. In both cases, over a period of 6 months after placement of the non-vascularized abdominal rectus muscle fascia, the wound contracted, granulation tissue gradually covered the wound, and healing occurred, giving an intact abdominal wall. The abdominal rectus muscle fascia from a deceased donor can be used in a definite procedure for closure of the abdominal wall either at the time of transplant or later when a suitable rectus muscle fascia graft becomes available.

Introduction Biliary anastomotic strictures (AS) occur in around 30% of patients following liver transplantation and are treated by endoscopic dilatation and plastic stent (PS) insertion. However, AS frequently recur and patients require multiple procedures. The Kaffes stent (KS, Taewoong Medical) is a removable, covered metal stent designed to be deployed across AS. Methods To examine outcomes in patients with AS, we compared a recent cohort of patients treated using KS with a historical cohort of patients who received PS. Results The 22 patients (12 females) treated by KS had mean age 55 (range 22–69) years; 11 patients had DBD and 11 DCD grafts; mean cold ischaemia time was 9.6±3.3 hours. Four patients had failed previous treatment with PS. To date, 16 patients have had KS removed. The 69 patients (20 female) treated by PS were similar, mean age 51 (range 28–79) years; 47 patients had DBD and 22 DCD grafts; mean cold ischaemia time was 8.9±3.1 hours. AS resolved after one deployment of KS in 14 out of 16 patients (88%) compared to 26 out of 69 patients (38%) receiving their first PS (Relative Risk of persistent stricture (KS vs PS)=0.2, 95% CI 0.05–0.74; p=0.016; number to treat by KS for one benefit=2, 95% CI 1.3–4.0). There were no complications, including stent migration, after KS compared to 6 (8.4%) in the PS group (3 cholangitis, 2 pancreatitis, and 1 bleeding). All KS were removed successfully, although 1 stent needed 2 attempts because of wire migration. Following initial ERCP, PS patients required more ERCPs (mean 2.71 vs 1.13 more; p Conclusion Our data indicate that the KS is a promising Method for managing post-transplant AS because the majority of strictures are treated by deployment of a single stent at first ERCP.

Mitochondria have their own genomic, transcriptomic and proteomic machinery but are unable to be autonomous, needing both nuclear and mitochondrial genomes. The aim of this work was to use computational biology to explore the involvement of Mitochondrial microRNAs (MitomiRs) and their interactions with the mitochondrial proteome in a clinical model of primary non function (PNF) of the donor after cardiac death (DCD) liver. Archival array data on the differential expression of miRNA in DCD PNF was re-analyzed using a number of publically available computational algorithms. 10 MitomiRs were identified of importance in DCD PNF, 7 with predicted interaction of their seed sequence with the mitochondrial transcriptome that included both coding, and non coding areas of the hypervariability region 1 (HVR1) and control region. Considering miRNA regulation of the nuclear encoded mitochondrial proteome, 7 hypothetical small proteins were identified with homolog function that ranged from co-factor for formation of ATP Synthase, REDOX balance and an importin/exportin protein. In silico, unconventional seed interactions, both non canonical and alternative seed sites, appear to be of greater importance in MitomiR regulation of the mitochondrial genome. Additionally, a number of novel small proteins of relevance in transplantation have been identified which need further characterization.

The imbalance between the number of potential beneficiaries and available organs, originates the search for new therapeutic alternatives, such as Hepatocyte transplantation (HT).Even though this is a treatment option for these patients, the lack of unanimity of criteria regarding indications and technique, different cryopreservation protocols, as well as the different methodology to assess the response to this therapy, highlights the need of a Consensus Conference to standardize criteria and consider future strategies to improve the technique and optimize the results.Our aim is to review and update the current state of hepatocyte transplantation, emphasizing the future research attempting to solve the problems and improve the results of this treatment.

While most human T cells express the CD28 costimulatory molecule constitutively, it is well-known that age, inflammation, and viral infection can drive the generation of CD28null T cells. In vitro studies have demonstrated that CD28null cell effector function is not impacted by the presence of the CD28 costimulation blocker belatacept. As such, a prevailing hypothesis suggests that CD28null cells may precipitate costimulation blockade-resistant rejection. However, CD28+ cells possess more proliferative and multi-functional capacity, factors that may increase their ability to successfully mediate rejection. Here, we performed a retrospective immunophenotypic analysis of adult renal transplant recipients who experienced acute rejection on belatacept treatment as compared to those that did not. Intriguingly, our findings suggest that patients possessing higher frequency of CD28+ CD4+ TEM prior to transplant were more likely to experience acute rejection following treatment with a belatacept-based immunosuppressive regimen. Mechanistically, CD28+ CD4+ TEM contained significantly more IL-2 producers. In contrast, CD28null CD4+ TEM isolated from stable belatacept-treated patients exhibited higher expression of the 2B4 coinhibitory molecule as compared to those isolated from patients who rejected. These data raise the possibility that pre-transplant frequencies of CD28+ CD4+ TEM could be used as a biomarker to predict risk of rejection following treatment with belatacept.

Dehydroepiandrosterone (DHEA) is a steroid secreted primarily by the adrenal gland and plays an important role as the primary precursor of many important sex steroids. The negative correlation between age and the secretion of DHEA (I) and in its sulfate form (II, DHEA-S) has been documented in human studies. Serum DHEA (I) and/or DHEA-S (II) levels have been associated with central nervous system function, immunity, cardiovascular functions, insulin sensitivity, and body composition.A high-performance liquid chromatography/ion trap mass spectroscopic method with sonic spray ionization (SSI) for the quantification of individual and total urinary 17-ketosteroid sulfates was developed. This quantification method had broad linearity range, low detection limit and high throughput. The amount of 17-KS-S, normalized by creatinine, in urine secreted over 24 hours versus that in early morning urines was found inversely correlated to age for both genders.

A diaphragmatic hernia (DH) is a rare complication of pediatric liver transplantation (LT), with multiple factors implicated in the pathophysiology. It is a potentially life-threatening condition in the absence of early recognition and surgical treatment. A DH after LT has been reported in 16 patients in 7 case series. We report 10 cases from our institution and review the published literature to understand the underlying pathophysiology. The study sample included all children (18 years of age) who underwent LT from October 1989 to August 2013 at our center and subsequently presented with a DH. Among 4433 LT procedures performed in this time period, 1032 were for children. Ten DH cases were recognized, and risk factors were assessed. The mean age at diagnosis was 4.9 years, all patients with a DH received left lateral segment split grafts, and the mean graft weight was 248 ± 41 g with a mean graft-to-recipient body weight ratio (GBWR) of 3% ± 1.22% (range = 1.7%-5.0%). The mean cold ischemia time was 510.7 ± 307.6 minutes (range = 60-900 minutes). Six patients had a primary abdominal muscle closure, 3 had a temporary Silastic mesh closure, and 1 had a skin closure only. Postoperative ascites and pleural effusion did not appear to be significant risk factors. All 10 children presented with a right posterolateral DH, with 1 also having a left DH. The small bowel was herniated in the majority. All patients underwent prompt surgical intervention without complications. An early age, a split graft, and a high GBWR may be risk factors for a DH. A high index of suspicion and prompt surgical intervention minimize complications.

RESUMEN Se presentan 2 casos de acidosis tubular re­nal de tipo distal, a propdsito de los cuales se caracteriza la enfermedad y se comentan las po~ sibilidades terapeuticas. REFERENCIAS 1.— Allbright F.; Burnett CH Parson, W. Reifenstein EC; Roos A. Osteomalacia and late rickets. Medi­cine 25: 399, 1946. 2.—Lightwood, R; Payne W. W.; Black, J. A, Infantile renal acidosis Pediatrics 12: 628, 1953. 3.— Rodriguez Soriano, J.; Boichis, H.; Stark, H.; Edel-mann, C. M. Proximal Renal Tubular. Acidosis = a defect in bicarbonate reabsorption. Pediat Res. 1: 81, 1967. 4.— Rodriguez Soriano, J.; Boichis, H.; Edeimann, C. Bicarbonate reabsorption and Hydrogen ion excretion in children with renal tubular acidosis. J. of Pediat. 71: 802, 1967. 5.— Edeimann, C M.; Boichis, H.; Rodriguez Soriano, J.; Stark, H. The renal response of children to acute ammonium chloride acidosis. Pediat Res. 1: 452, 1967. 6.— Broyer, M.; Proesmans, W.; Royer, P. La titration des bicarbonates chez 1'enfant normal au cours de diverses nephropathies. Rev. Franc. Etud Clin. Biol. 14: 556, 1969. 7.— Morris, Re. Renal Tubular Acidosis. Mechanism, classification and implications. New Eng. J. Med. 281: 1405, 1969. 8.— Royer, P.; Broyer, M. L'acidose renale au cours des tubulapathies cong^nitales. Actualites Nephro-logiques de l'Hopital Necker. Editions Medicales Flammarion. Paris, 1967. 9.— Toursel, F. Exploration de la founction renale d' acidification par les epreuves de surchage acide chez 1'enfant. Rev. de Pediat: 8: 115, 1972. 10.— Rodriguez Soriano, J. The renal regulation of aci-de-base. Balance and the disturbances noted in re­nal tubular acidosis. Pediat Clin, of North Ame­rica 18: 529, 1971. 11.— Straiiss, M. B.; Welt, L. G. Enfermedades del rin6n. El Ateneo, Buenos Aires, 1966. 12.— Royer, P.; Mathieu, M.; Habib, R. Problemas ac­tuates de Nefrologia infantil. Ediciones Torey. Barcelona, 1965. 13.— Maccioni, A.; Saitua, M. T.; Oxman, S. Mecanis-mos renales y extrarrenales de compensaci6n en un caso de acidosis tubular cronica idiopatica. Rev. Chilena de Pediat. 39: 395, 1968. 14.— Dundon, Sheamus. Treatment of osteomalacia of renal tubular acidosis. Lancet 2: 1204, 1972. 15.— Stickler, G. B.; Bergen, B. J. A review: Short sta­ture in renal disease. Pediat. Res. 7: 978, 1973. 16.— Richards, P.; Chamberlain, M. J.; Wrong, O. M. Treatment of osteomalacia of renal tubular aci­dosis by sodium bicarbonate alone. Lancet 2: 994, 1972. 17.—-Lin, S.; Chan, J. C. M. Classical (distal) renal tu­bular acidosis: endogenous acid production. Pediat. Res. 8: 457, 1974. 18._ Farrell, R. M.; Horwith, M.; Muecke, E. C. Renal tubular acidosis and nephrocalcinosis diagnosis and clinical management. J. of Urol. 11: 429, 1974. 19.— Heidbieder, E.; Heuriemann, H.; Heidland, A.; Krempien, B. K. Treatment of renal tubular aci­dosis and osteomalacia by salidiuretics. Lancet 1: 52, 1973. 20.— Guigard, J. P.; Torrado, A. Proximal renal tubu­lar acidosis in vitamin D. Deficiency rickets. Acta Pediat. Scand. 62: 543, 1973. 21.— Rampini, S.; Fanconi, A.; Illig, R.; Prader, A. Ef­fect of hydrochlorothiazide on proximal renal tu­bular acidosis in a patient with idiopathic "de Toni-Debre" Fanconi syndrome". Helv. Paediat. Acta 23: 13, 1968. 22.— Kurtzman, N. A. Regulation of renal bicarbonate reabsorption by extracellular volumen J. of Clin. Invest. 49: 586, 1970.