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In recent years, self-expandable metallic stents (SEMSs) have emerged as a promising treatment alternative for the bridging and sealing of esophageal perforations and extensive anastomotic leaks after esophageal resection or total gastrectomy. A 56-year-old woman underwent a total gastrectomy with Roux-en-Y end-to-side esophagojejunostomy for a gastric signet ring cell carcinoma. Ten days later, esophagogastroduodenoscopy showed a 2 cm fistula in the distal end of the Roux limb of the anastomosis. This was confirmed by gastrografin esophagography. The patient was started on total parenteral nutrition. Having deemed clipping treatment for this fistula unfeasible, we decided to insert a partially silicone-coated SEMS (Evolution Controlled Release Esophageal Stent System, Cook Medical, Winston-Salem, N.C., USA). The stent was removed after ten days. Gastrografin esophagography showed no further contrast extravasation, and esophagogastroduodenoscopy showed closure of the fistula. No clinical complications were observed, and the patient was able to start normal per os nutrition. In conclusion, the treatment of symptomatic leaks in patients who have undergone esophagojejunostomy is challenging, and leakage from the jejunal stump can be a potentially serious complication. In the treatment of leakage after total gastrectomy, plastic stents (which are either too light or exercise too little radial force) and totally covered metallic stents may not adhere sufficiently to the esophagojeujunal walls and, as a result, migrate beyond the anastomosis. The promising results of this report suggest that early stenting, using a partially silicone-coated SEMS, is a feasible alternative to surgical treatment in this category of patients.

A wide spectrum of common and uncommon diffuse liver diseases affecting neonatal and pediatric liver transplant candidates is presented and analyzed using 16 and 64 multi-detector row helical CT (MDCT) and 1.5 T MRI fast imaging. Correlation of imaging findings and explanted liver or histology is illustrated in representative cases. Associated uncommon congenital anomalies are shown. In conclusion, in pediatric liver transplant candidates, 16-MDCT and 1.5 T fast MRI are useful for diagnosis and staging of liver disease, as well as for the evaluation of associated congenital anomalies.

Khan Z, Sciveres M, Salis P, Minervini M, Maggione G, Cintorino D, Riva S, Gridelli B, Emma F, Spada M. Combined split liver and kidney transplantation in a three-year-old child with primary hyperoxaluria type 1 and complete thrombosis of the inferior vena cava. Pediatr Transplantation 2011: 15: E64–E70. © 2009 John Wiley & Sons A/S. Abstract: PH1 is an inborn error of the metabolism in which a functional deficiency of the liver-specific peroxisomal enzyme, AGT, causes hyperoxaluria and hyperglycolic aciduria. Infantile PH1 is the most aggressive form of this disease, leading to early nephrocalcinosis, systemic oxalosis, and end-stage renal failure. Infantile PH1 is rapidly fatal in children unless timely liver-kidney transplantation is performed to correct both the hepatic enzyme defect and the renal end-organ damage. The surgical procedure can be further complicated in infants and young children, who are at higher risk for vascular anomalies, such as IVC thrombosis. Although recently a limited number of children with IVC thrombosis have underwent successful kidney transplantation, successful multi-organ transplantation in a child with complete IVC thrombosis is quite rare. We report here the interesting and technically difficult case of a three-yr-old girl with a complete thrombosis of the IVC, who was the recipient of combined split liver and kidney transplantation for infantile PH1. Although initial delayed renal graft function with mild-to-moderate acute rejection was observed, the patient rapidly regained renal function after steroid boluses, and was soon hemodialysis-independent, with good diuresis. Serum and plasma oxalate levels progressively decreased; although, to date they are still above normal. Hepatic and renal function indices were at, or approaching, normal values when the patient was discharged 15-wk post-transplant, and the patient continues to do well, with close and frequent follow-up. This is the first report of a successful double-organ transplant in a pediatric patient presenting with infantile PH1 complicated by complete IVC thrombosis.

Objective: To report the efficacy, tolerability, and safety of the dopamine agonist pramipexole in a series of 5 patients affected by inherited 6-pyruvoyl tetrahydropterin synthase (PTPS) deficiency and needing l-3,4 dihydroxyphenylalanine (l-dopa) therapy. Methods: Patients included 4 males and 1 female with ages ranging from 2 to 26 years. Their medication included tetrahydrobiopterin (BH4), 5-hydroxytryptophan, l-dopa, carbidopa, selegiline, and entacapone. All experienced residual symptoms of dopamine deficiency, movement and behavioral disability, and complications of l-dopa therapy, associated with fluctuating hyperprolactinemia. Patients had full assessment of clinical and biochemical condition, including evaluation by an adapted Unified Parkinson9s Disease Rating Scale (UPDRS) and measurement of plasma prolactin (PRL) and catecholamines, before and after a 6-week trial with pramipexole. Pramipexole was administered twice daily as an adjunct to l-dopa therapy in dosages upwardly titrated, with a concurrent reduction of l-dopa dosage. Clinical follow-up went on for 1 year. Results: Pramipexole was well tolerated by all patients, with marked improvement and stabilization of their clinical picture. The mean improvement on the total UPDRS score was 43% (range 33.3%–55.6%) from baseline. Diurnal profiles of plasma PRL normalized and plasma catecholamine levels lasted unchanged. The daily administrations of l-dopa were curtailed from 3 or 4 to 2, and the l-dopa dosage was reduced up to 40%. Conclusions: The addition of pramipexole to the treatment of 6-pyruvoyl tetrahydropterin synthase deficiency improves the results of l-3,4 dihydroxyphenylalanine therapy. Similar benefits may be expected in other forms of inherited tetrahydrobiopterin deficiency.

We analyze our experience with the management of biliary strictures (BSs) in 27 pediatric patients who underwent liver transplantation with the diagnosis of BS. Mean recipient age was 38 months (range, 2.5-182 months). In all patients percutaneous transhepatic cholangiography, biliary catheter placement, and bilioplasty were performed. In 20 patients the stenoses were judged resolved by percutaneous balloon dilatation and the catheters removed. Mean number of balloon dilatations performed was 4.1 (range, 3-6). No major complications occurred. All 20 patients are symptom-free with respect to BS at a mean follow-up of 13 months (range, 2-46 months). In 15 of 20 patients (75%) one course of percutaneous stenting and bilioplasty was performed, with no evidence of recurrence of BS at a mean follow-up of 15 months (range, 2-46 months). In 4 of 20 patients (20%) two courses of percutaneous stenting and bilioplasty were performed; the mean time to recurrence was 9.8 months (range, 2.4-24 months). There was no evidence of recurrence of BS at a mean follow-up of 12 months (range, 2-16 months). In 1 of 20 patients (5%) three courses of percutaneous stenting and bilioplasty were performed; there was no evidence of recurrence of BS at a mean follow-up of 10 months. In conclusion, BS is a major problem following pediatric liver transplantation. Radiological percutaneous treatment is safe and effective, avoiding, in most cases, surgical revision of the anastomosis.

We report one case of percutaneous recanalization of an hepatico-jejunostomy, using Colapinto needle, in a two-yr-old patient after partial liver transplantation and occlusive anastomotic biliary stricture non-crossable with conventional interventional radiology techniques. The procedure was successfully performed and followed by biliary trans-anastomotic catheter placement. Later, the patient underwent multiple session of conventional percutaneous balloon dilatation of the anastomosis as a good flow of contrast from bile ducts to bowel loops was achieved. The patient is now without percutaneous biliary catheter since 10 months in good general conditions and with good liver function tests.

Ultrasound (US) guidance is currently used for placement of wire-guided thoracic drains, and its use is associated with a decreased risk of complications. However, most studies conducted to date in this field have been performed on adult patients. The aim of this study was to report the technical success and complication rates observed during real-time US-guided placement of a thoracic pigtail catheter in pediatric liver-transplant recipients with symptomatic pleural effusion.This was a single-center retrospective review of the clinical records and images from pediatric liver-transplant patients with symptomatic pleural effusion who had undergone real-time US-guided pleural-space puncture followed by placement (via the Seldinger technique) of a pigtail catheter for drainage, between May 2006 and June 2014.We identified 25 patients who had undergone 41 pigtail catheter-placement procedures during the study period. The patients' mean age (± SD) was 4.2 ± 3.9 years (range, 2 months to 16 years), and their mean weight was 14.2 ± 7.2 kg (range, 4.5-33 kg). Seventeen procedures had been performed in the intensive care unit, and 8, in patients undergoing mechanical ventilation. Twelve of the 41 procedures had been performed in patients with altered hemostasis (ie, platelet count50 × 10(3) /μl and/or international normalized ratio1.5). The size of the pigtail catheters ranged from 5 F to 8.5 F. The technical success rate was 100%, with no major complications such as pneumothorax or hemothorax. Accidental dislocation of the catheter occurred in four patients (9%) over 3-10 days after the first procedure.In our experience, real-time US-guided pleural-space puncture, performed at bedside, with the patient in the supine position, followed by placement of a pigtail catheter for drainage of effusion, is safe to use and has a high rate of technical success in pediatric patients. © 2015 Wiley Periodicals, Inc. J Clin Ultrasound 44:284-289, 2016.

With conventional dietary treatment, the clinical course of methylmalonic acidemia due to cobalamin-unresponsive methylmalonyl-CoA mutase (MCM) deficiency is characterized by the persistent risk of recurrent life-threatening decompensation episodes with metabolic acidosis, hyperammonemia, and coma. Liver transplant has been proposed as an alternative treatment and anecdotally attempted in the last 2 decades with inconsistent results. Most criticisms of this approach have been directed at the continuing risk of neurologic and renal damage after transplant. Here, we report the perioperative and postoperative clinical and biochemical outcomes of 2 patients with severe MCM deficiency who underwent early liver transplant. In both cases, liver transplant allowed prevention of decompensation episodes, normalization of dietary protein intake, and a marked improvement of quality of life. No serious complications have been observed at 12 years’ and 2 years’ follow-up, respectively, except for mild kidney function impairment in the older patient. On the basis of our experience, we strongly suggest that liver transplant should be offered as a therapeutic option for children with cobalamin-unresponsive MCM deficiency at an early stage of the disease.

Postoperative plasma lactate clearance has been established as an important prognostic factor for liver resection morbidity and mortality. The aim of this study was to analyse continuous monitoring of plasma lactate in patients submitted to extended hepatectomy (EH) with special attention to those who received preoperative portal vein branch embolization (PVE) to augment the future remnant liver. In this single center retrospective study, a full revision of 45 medical records was performed from patients who underwent EH at ISMETT from October 1999 to August 2013. Plasma lactates from admission to ICU to day 5 were recorded. Postoperative lactate clearance (ΔLAC) was defined as lactate at postoperative day 5 minus lactate at ICU presentation (hour 0). ΔLAC was analysed in relation to total hospital stay and 90 days' perioperative morbidity and mortality, using Clavien-Dindo classification, and by presence or absence of PVE. Forty-one right and four left EH were performed. 17 patients underwent previous PVE with a mean of 44 ± 28.9 days-to-surgery time and a 24 ± 8.3% degree of hypertrophy. In 39 cases (86.7%), a malignant etiology was the indication for EH, length of surgery was 486 ± 122 min with a median of 300 ml of blood transfusion. In 25 patients, a Clavien grade IIIa or worst complication has been experienced, and in three cases the death occurred during the first 3 months after EH. The median length of hospitalization was 11 days. In patients with preoperative PVE a significative association with an early post-resectional lactate clearance was obtained (p 0.01). Conversely, the univariate analysis measured by t test did not show any significative associations between ΔLAC and a median time of hospital stay longer than 11 days (p 0.08), or the onset of any complications (p 0.67) and of a Clavien's grade of complications ≥IIIa patients (p 0.48). After adjusting for co-variables, results of the multivariate logistic regression analyses confirmed that ΔLAC is not independent or significant predictor for initial poor liver function following EH. In our single center experience, the continuous monitoring of postoperative lactate clearance did not work as an early marker of postoperative liver dysfunction following EH. Although lactate clearance, worked as guide having a clinical utility in the ICU statement for hemodynamic optimization and systemic fluid balance management.

Late portal vein thrombosis with cavernomatous replacement has been reported in 4.5 % of pediatric patients who have undergone partial liver transplantation. In such cases, minimally invasive radiological treatments have a high failure rate. We report a successful case of percutaneous recanalization of the portal vein remnant, and subsequent stent placement, in a pediatric patient who underwent left lateral split liver transplantation with cavernomatous replacement of the portal vein.

Donor-derived infections due to multidrug-resistant bacteria are a growing problem in solid organ transplantation, and optimal management options are not clear. In a 2-year period, 30/214 (14%) recipients received an organ from 18/170 (10.5%) deceased donors with infection or colonization caused by a carbapenem-resistant gram-negative bacteria that was unknown at the time of transplantation. Among them, 14/30 recipients (47%) received a transplant from a donor with bacteremia or with infection/colonization of the transplanted organ and were considered at high risk of donor-derived infection transmission. The remaining 16/30 (53%) recipients received an organ from a nonbacteremic donor with colonization of a nontransplanted organ and were considered at low risk of infection transmission. Proven transmission occurred in 4 of the 14 high-risk recipients because donor infection was either not recognized, underestimated, or not communicated. These recipients received late, short or inappropriate posttransplant antibiotic therapy. Transmission did not occur in high-risk recipients who received appropriate and prompt antibiotic therapy for at least 7 days. The safe use of organs from donors with multidrug-resistant bacteria requires intra- and inter-institutional communication to allow appropriate management and prompt treatment of recipients in order to avoid transmission of infection.

Patients with growing and nonresectable liver hemangiomas should be followed up by a transplant center with extensive experience in complex liver disease. They could be treated on an emergency basis with orthotopic liver transplantation, with an expectation of good long-term results.We describe the case of a 37-year-old woman with liver hemangiomatosis followed up for 8 years, who presented with bleeding requiring transfusions and developed hemodynamic instability. We listed her for emergency transplant before her sister's living donor work-up could be completed. A liver from a cadaveric donor became available at a small local hospital with no experience in organ donation. Tele-intensive care unit (tele-ICU) technology was used for providing clinical data electronically to physicians, nurses, and other critical care specialists, creating medication orders, and communicating with on-site caregivers to implement changes in donor care.The recipient was transplanted on an emergency basis with a specific customization and application of the telemedicine system in the management of the organ procurement by the recipient team. Tele-ICU technology was used for providing an effective intensive care unit service, managing and stabilizing the deceased donor and allowing the procurement to be carried out uneventfully.Tele-ICU technology could be a promising resource for emergency transplantation, reducing the urgent need for a living donation and allowing prompt recipient team management of the deceased donor. Our first tele-ICU case offers early confirmation of the feasibility of the telemedicine system in deceased-donor management.

Avoidance of corticosteroids could be beneficial after pediatric liver transplantation (LTx). To test this hypothesis, we performed a randomized prospective study to compare immunosuppression with tacrolimus (TAC) and steroids versus TAC and basiliximab (BAS) after pediatric LTx. Seventy-two patients were recruited, 36 receiving TAC and steroids and 36 TAC and BAS. The primary endpoint was the occurrence of the first rejection episode. Secondary endpoints were the cumulative incidence and severity of rejection, patient and graft survival, and incidence of adverse events. Overall 1-year patient and graft survival rates were 91.4% and 85.5% in the steroid group, and 88.6% and 80% in the BAS group (p = NS). Patients free from rejection were 87.7% in the BAS group and 67.7% in the steroid group (p = 0.036). The use of BAS was associated with a 63.6% reduction in incidence of acute rejection episodes. Overall incidence of infection was 72.3% in the steroid group and 50% in the BAS group (p = 0.035). We conclude that the combination of TAC with BAS is an alternative to TAC and steroid immunosuppression in pediatric LTx, which allows for a significant reduction in the incidence of acute rejection and infectious complications.

The present study aimed to characterize mutant alleles in Mucopolysaccharidosis II and evaluate possible reduction of mRNA amount consequent to nonsense-mediated or nonstop mRNA decay pathways. A combination of different approaches, including real-time RT-PCR, were used to molecularly characterize seventeen patients. Fifteen alleles were identified and nine of them were new. The novel alleles consisted of three missense mutations (p.S71R, p.P197R, p.C432R), two nonsense (p.Q66X, p.L359X), two frameshifts (p.V136fs75X, p.C432fs8X), one allele carrying two in-cis mutations [p.D252N;p.S369X], and a large deletion (p.G394_X551). Analysing these results it emerged that most of the alterations resulted in mutants leading to mRNAs with premature termination codons, and therefore, potentially sensitive to mRNA surveillance pathway. By using real-time RT-PCR, the mRNAs resulting (i) from substitutions that changed one amino acid to a stop codon (L359X, and S369X), or caused the shifted reading frame with premature introduction of a stop codon (C432fs8X), (ii) from large deletion (p.G394_X551) that included the termination codon, seemed to be subject to degradation by nonsense-mediated (i) or nonstop decay (ii) mechanisms, as mRNA was strongly underexpressed. On the contrary, two mutations (Q66X and V136fs75X) produced transcripts evading mRNA surveillance pathway despite both of them fulfilled the known criteria. These results confirm the wide variability of the mRNA expression levels previously reported and represent a further exception to the rules governing susceptibility to nonsense-mediated decay. A close examination of the molecular basis of the disease is becoming increasingly important for optimising the choices of available or forthcoming therapies such as, enzyme replacement therapy or enzyme enhancement therapy.

The aim of this study was to determine the impact of two reperfusion techniques on the peri-operative hemodynamic changes and early post-operative graft function of adult patients undergoing orthotopic liver transplantation. Material and methods: From June 2003 to May 2004, 50 consecutive liver transplants were performed and divided into two groups: group A, 25 patients, portal vein flush with 500 cm3 of Ringer's lactate without vena caval venting. Group B, 25 patients, vena caval venting with no portal vein flush. Donor and recipient characteristics were similar in both groups. Sixty-four different parameters were analyzed, and Pearson's χ2 test and t-test were used for statistical analysis, p0.05. Results: One patient (4%) in group B experienced a post-reperfusion syndrome (PRS). Pearson's χ2 test found a significant relationship between the analyzed parameters and the two different reperfusion techniques for 10 parameters (t-test analysis showed a significant difference between the two groups in favor of group A). Conclusions: In our transplant center, portal vein flush without vena caval venting provided a lower incidence of hemodynamic changes in the peri-operative period after liver transplantation and earlier recovery of the graft function.

Infections by herpesviruses may have severe complications in liver transplant patients. Although prophylactic varicella zoster virus vaccination is strongly recommended and widely applied, severe infection may still occur. We report the case of systemic chronic varicella, which developed in a liver allograft recipient, unresponsive to antiviral drug treatment, successfully treated by varicella zooster-specific CTL. Graft failure ensued, likely, because of massive cytolysis of infected hepatocytes. The patient, who was re-transplanted in the absence of signs of varicella zooster reactivation, is now well and disease free 3 yr after second liver transplant.

Late graft dysfunction (GD) associated with the development of autoantibodies is a common event after pediatric liver transplantation (OLTx) and can present in 2 clinicohistological subsets: de novo autoimmune hepatitis (DNAH) and early chronic rejection (ECR). Sixty out of 247 children developed autoantibodies after OLTx. GD was demonstrated in 22 (37%); based on histology, patients were divided in a DNAH and an ECR group. Portal/periportal inflammatory infiltrate with interface/lobular hepatitis was suggestive for DNAH. Pericentral hepatocytes; confluent dropout with a variable degree of central vein endothelitis, but not with ductopenia (loss of >50% of interlobular bile ducts), was diagnosed as ECR. Nine patients had DNAH and 13 ECR. Five out of 9 in the DNAH group were on cyclosporin (CsA) and 4/9 were on tacrolimus (Tac). In the ECR group, 11 children were treated with CsA and 2 with Tac. All DNAH patients had normal liver function tests on steroids and azathioprine (AZA). Five patients with ECR recovered by increasing calcineurin inhibitors (CNIs) dosage, but in 8/13, including 7 switched from CsA to Tac, AZA and steroids were added to obtain remission of disease. Two patients developed late chronic rejection. DNAH and ECR associated with autoantibodies are forms of late GD after OLTx. DNAH improves after standard treatment of autoimmune hepatitis. ECR has a good response to increased doses of CNIs, although ductopenic chronic rejection may occur. In conclusion, the early differential diagnosis of these conditions and an appropriate treatment seem to allow good overall results reflected by a graft survival of more than 90%.

Study objective The identification of risk factors for recurrent motor vehicle crashes is the basis for prevention, but few studies have been published on predictors of recurrence. Our objective is to determine the main variables predicting recurrent crashes in subjects attending an emergency department (ED) for injuries after motor vehicle crash. Methods During a 5-year follow-up period, we studied 2,354 consecutive adult subjects treated in the ED after a motor vehicle crash in 1998. The variables of the original event were tested for predicting recurrence in a Cox proportional hazard model. Results During follow-up, 390 of 2,325 (16.8%) survivors were treated for injury after a new crash. The overall event rate was 34 per 1,000 subject-years. Four variables (age ≤32 years, male sex, nighttime crash, and blood alcohol concentration >50 mg/dL) were identified as independent predictors of recurrent crash. After adjustment for sex, age, and nighttime, alcohol was the leading predictor (relative risk 3.73; 95% confidence interval 3.00 to 4.64). In the presence of the 4 variables, the recurrence rate was as high as 145 (117 to 175) events per 1,000 subject-years, and alcohol per se accounted for more than 75% of events. In the absence of the 4 variables, the rate was as low as 11 (7 to 17) events per 1,000 subject-years. Conclusion Alcohol was the most powerful behavioral factor predicting recurrent events in subjects treated in an ED for injury after motor vehicle crash, along with young age, male sex, and nighttime.

The use of damage control techniques, including interventional radiology techniques, liver packing, and planned reoperation, has contributed to current management of complex liver injury. The training of trauma surgeons must include a familiarity with all such techniques and formal training in hepatobiliary surgery or liver transplantation. Appropriate decision-making for formal resections in patients who have been stabilized and then require subsequent surgical care is based on a mandatory evaluation of massive lobar or multilobar damage and intra- or retrohepatic venous injuries with hemorrhage that have been temporally controlled by packing or other measures during surgical management at initial admission. Stabilization with damage control techniques and the transfer, after the acute period, of the patient to a transplant center is the gold standard for centers that lack the surgical and medical expertise of transplant referral centers. Technical skills in advanced hepatobiliary surgery, patient hemodynamic and resuscitation, diagnostic evaluations, operative indications by grade of injury, selection criteria for surgical management, and criteria for the choice of operation are mandatory for indicating formal liver resection as initial or delayed management of patients with complex liver trauma.

Urea Cycle Disorders ( UCD ) are among the most common genetic diseases of the metabolism and ornithine transcarbamylase deficiency (OTC), an X-linked defect is the most frequent among them. It is responsible for hyperammonemia that can lead to chronic neurological illness and potentially to death in case of delayed diagnosis and treatment. With regards to the OTC deficiency there is great clinical heterogeneity with early-onset phenotypes with mostly poor prognosis and late-onset phenotypes with a better one. In the article it is reported the case of a 8 years old patient with diagnosis of OTC deficit with late-onset phenotype. The kid was brought to our hospital because of continuous vomiting and gastro- intestinal disorders, associated with irritability and lethargy later resulted into coma. Measurement of plasma ammonia concentration, followed by measurement of plasma amino acid and urine orotic acid levels allowed to diagnose the OTC deficit, lately confirmed by molecular genetic studies. The patient has been promptly treated with Sodium Phenylbutyrate, Arginine and discontinuing the protein intake. Gradually the ammonemia value decreased, and general and neurological conditions improved with resolution of the coma. To conclude, for patients presenting unexplained neurological symptoms, confusion and decreased level of consciousness, up to coma, urea cycle disorders and in particularly OTC deficiency should be considered in the differential diagnosis and an urgent ammonia level determined. In case of hyperammonemia, the treatment should be started immediately , even without a precise ethiologic diagnosis.

Fetal hepatocytes have a high regenerative capacity. The aim of the study was to assess treatment safety and clinical efficacy of human fetal liver cell transplantation through splenic artery infusion. Patients with endstage chronic liver disease on the waiting list for liver transplantation were enrolled. A retrospectively selected contemporary matched-pair group served as control. Nonsorted raw fetal liver cell preparations were isolated from therapeutically aborted fetuses. The end points of the study were safety and improvement of the Model for End-Stage Liver Disease (MELD) and Child-Pugh scores. Nine patients received a total of 13 intrasplenic infusions and were compared with 16 patients on standard therapy. There were no side effects related to the infusion procedure. At the end of follow-up, the MELD score (mean ± SD) in the treatment group remained stable from baseline (16.0 ± 2.9) to the last observation (15.7 ± 3.8), while it increased in the control group from 15.3 ± 2.5 to 19 ± 5.7 ( p = 0.0437). The Child-Pugh score (mean ± SD) dropped from 10.1 ± 1.5 to 9.1 ± 1.4 in the treatment group and increased from 10.0 ± 1.2 to 11.1 ± 1.6 in the control group ( p = 0.0076). All treated patients with history of recurrent portosystemic encephalopathy (PSE) had no further episodes during 1-year follow-up. No improvement was observed in the control group patients with PSE at study inclusion. Treatment was considered a failure in six of the nine patients (three deaths not liver related, one liver transplant, two MELD score increases) compared with 14 of the 16 patients in the control group (six deaths, five of which were caused by liver failure, four liver transplants, and four MELD score increases). Intrasplenic fetal liver cell infusion is a safe and well-tolerated procedure in patients with end-stage chronic liver disease. A positive effect on clinical scores and on encephalopathy emerged from this preliminary study.

Objectives: The present study assesses the safety of ultrasound (US)-guided percutaneous liver biopsies (PLBs) within pediatric liver allograft recipients, describes the pathological results according to early (� 12 months) and late (>12 months) posttransplantation periods, and analyzes the value of liver function tests (LFTs) and Doppler US variables in determining these results. Methods: A total of 219 US-guided PLBs in 85 pediatric patients with liver transplant (mean age 7 � 5 years, range: 6 months to 18 years) performed between March 2005 and May 2012 were retrospectively evaluated at a single institution. Doppler US and LFT evaluation (including total bilirubin, alanine aminotransferase, aspartate aminotransferase, g-glutamyl transferase, alkaline phosphatase) occurred within 1 day of early (n ¼ 92, 42%) and late term (n ¼ 127, 58%) posttransplantation biopsies. Results: The rate of major complications (hemorrhage requiring blood transfusion) was 0.91% (n ¼ 2). The early versus late term biopsy results, respectively, included: cholestasis at 36% versus 18% (P ¼ 0.003), minimal changes 16% versus 24% (not significant [NS]), acute rejection 13% versus 5% (P ¼ 0.027), inflammatory diseases 15% versus 15% (NS), indeterminate acute rejection 11% versus 7% (NS), chronic rejection 4% versus 14% (P ¼ 0.017), fibrotic diseases 4% versus 12% (NS), and other 0% versus 5% (NS). Neither LFT nor US variables were correlated with pathological outcomes. Conclusions: The rate of complications in pediatric patients after US-guided liver biopsy is low. A range of pathological results exists between early and late posttransplantation liver biopsies. LFT and Doppler US findings are not predictors of pathological results.

PMM2-CDG (PMM2 gene mutations) is the most common congenital disorder of N-glycosylation. We conducted a nationwide survey to characterize the frequency, clinical features, glycosylation and genetic correlates in Italian patients with PMM2-CDG. Clinical information was obtained through a questionnaire filled in by the referral physicians including demographics, neurological and systemic features, neuroimaging data and genotype. Glycosylation analyses of serum transferrin were complemented by MALDI-Mass Spectrometry (MALDI-MS). Between 1996 and 2012, data on 37 Italian patients with PMM2-CDG were collected. All the patients with a severe phenotype were unable to walk unaided, 84 % had severe intellectual disability and 81 % microcephaly. Conversely, among 17 mildly affected patients 82 % had independent ambulation, 64 % had borderline to mild intellectual disability and 35 % microcephaly. Epilepsy and stroke-like events did not occur among patients with the mild phenotype. The rate and extent of systemic involvement were more pronounced in severely affected patients. The L32R misfolding mutation of the PMM2 gene occurred in 70 % of the patients with the mild phenotype and was associated with a less severe underglycosylation of serum Tf at MALDI-MS analyses. Despite their different disease severity, all patients had progressive (olivo)ponto-cerebellar atrophy that was the hallmark clinical feature for the diagnosis. A mild neurological phenotype of PMM2-CDG marked by preserved ambulatory ability and autonomy and associated with L32R mutation is particularly frequent in Italy. PMM2-CDG should be considered in patients with even mild developmental disability and/or unexplained progressive cerebellar atrophy.

Molecular analysis of 289 chromosomes has been performed in a cohort of phenylketonuria (PKU) patients whose ancestors lived in five Italian regions, Calabria, Campania, Piemonte, Puglia/Basilicata and Sicilia. Phenylalaninehydroxylase (PAH) gene mutations and minihaplotypes (combinations of PAH gene STR and VNTR systems) have been determined for 78.5 and 64%, respectively, of the chromosomes studied. 21 different minihaplotypes and 24 PKU mutations were found. Heterogeneity tests carried out for the frequencies of mutations and minihaplotypes show that the distribution of eight mutations and four minihaplotypes is statistically heterogeneous in the five Italian regions. Although the evolutionary rate of microsatellites or the age of these mutations is difficult to estimate with accuracy, our findings taken together show a genetic stratification of the Italian population. These results rule out allelic homogeneity of PKU at the molecular level between regions of Italy, yet minihaplotype data may be of practical use for a multistep approach to PAH gene genotyping.

Obscure gastrointestinal (GI) bleeding is defined as bleeding from the GI tract that persists or recurs, with no obvious etiology, after esophagogastroduodenoscopy (EGD), colonoscopy, and radiologic evaluation of the small bowel. We present the case of a 17-yr-old girl who for two years had been suffering from recurrent episodes of melena and/or enterorrhagia. Fifteen yr earlier she had undergone a split-liver transplant with Roux-en-Y biliary reconstruction. A series of endoscopic and radiologic investigations had failed to find the source of the bleeding. Suspecting the presence of ectopic varices, we decided to perform single-balloon enteroscopy (SBE). We observed and aspirated a large amount of fresh red blood in the afferent loop until we found the hepaticojejunostomy. On the edge of the biliary-enteric anastomosis we observed a vascular lesion 5 mm in diameter. Judging this ectopic varix to be the source of bleeding, we placed two endoclips. The second clip placement caused varix rupture with a consequent massive hemorrhage, emergently and successfully treated with cyanoacrylate sclerotherapy. No episodes of rebleeding were observed, and no complications occurred during the entire hospital stay, and after six months of follow-up. This report highlights the importance of afferent loop examination in patients with obscure GI bleeding who have undergone liver transplant with Roux-en-Y biliary reconstruction.

Langerhans' cell histiocytosis (LCH) is a disease of unknown pathogenesis, caused by clonal proliferation of Langerhans' cells. Liver involvement results in a cholangiopathy, which has the radiologic appearance of sclerosing cholangitis. Only 1 case of obstructive jaundice due to common bile duct stone in a patient with LCH has been described. We present a case of a 31-month-old child with LCH and liver involvement on the waiting list for liver transplantation. During the follow-up, there was a rapid onset of jaundice due to sludge and lithiasis. The patient was treated first with an endoscopic biliary plastic stent and then with percutaneous biliary drainage and bilioenteric anastomosis. © 2009 Wiley Periodicals, Inc. J Clin Ultrasound 2009

Persistent hyperinsulinemic hypoglycaemia of infancy (PHHI) is the most frequent cause of hypoglycaemia in infancy. Clinical presentation is heterogeneous, with variable onset of hypoglycaemia and response to diazoxide, and presence of sporadic or familial forms. Underlying histopathological lesions can be focal or diffuse. Focal lesions are characterised by focal hyperplasia of pancreatic islet-like cells, whereas diffuse lesions implicate the whole pancreas. The distinction between the two forms is important because surgical treatment and genetic counselling are radically different. Focal lesions correspond to somatic defects which are totally cured by limited pancreatic resection, whereas diffuse lesions require a subtotal pancreatectomy exposing to high risk of diabetes mellitus. Diffuse lesions are due to functional abnormalities involving several genes and different transmission forms. Recessively inherited PHHI have been attributed to homozygote mutations for the beta-cell sulfonylurea receptor (SUR1) or the inward-rectifying potassium-channel (Kir6.2) genes. Dominantly inherited PHHI can implicate the glucokinase gene, particularly when PHHI is associated with diabetes, the glutamate dehydrogenase gene when hyperammonaemia is associated, or another locus.