Orthotopic liver transplant for multifocal lymphangioendotheliomatosis with thrombocytopenia

An eight‐yr‐old female with a history of multifocal lymphangioendotheliomatosis and thrombocytopenia presented for MVT. The patient had multiple vascular lesions in the skin and stomach in infancy. Although her cutaneous lesions resolved with vincristine and methylprednisolone, her gastric lesions persisted. Eight yr later, she was diagnosed with portal hypertension and decompensating liver function despite therapy with bevacizumab, propranolol, furosemide, and spironolactone. Upon presentation, she was found to have a Kasabach–Merritt‐like coagulopathy in association with multiple lesions in her GI tract and persistent gastric lesions. Although treatment with methylprednisolone and sirolimus normalized her coagulation factors and d ‐dimer levels, she never developed sustained improvement in her thrombocytopenia. Her liver function continued to deteriorate and she developed hepatorenal syndrome. Given better outcomes after OLT in comparison with MVT, she underwent OLT, with the plan to manage her GI lesions with APC post‐transplant. Post‐transplant, her liver function and coagulopathy normalized, and GI tract lesions disappeared upon screening with capsule endoscopy. The patient is doing well, without recurrence of either GI lesions or thrombocytopenia, at 18 months after transplantation.     

Jejunal varices diagnosed by capsule endoscopy in patients with post‐liver transplant portal hypertension

Portal hypertension secondary to portal vein obstruction following liver transplant occurs in 5%‐10% of children. Jejunal varices are uncommon in this group. We present a case series of children with significant GI blood loss, negative upper endoscopy, and jejunal varices detected by CE. Case series of patients who had CE for chronic GI blood loss following liver transplantation. Three patients who had their initial transplants at a median age of 7 months were identified at our institution presenting at a median age of 8 years (range 7‐16 years) with a median Hgb of 2.8 g/dL (range 1.8‐6.8 g/dL). Upper endoscopy was negative for significant esophageal varices, gastric varices, and bleeding portal gastropathy in all three children. All three patients had significant jejunal varices noted on CE in mid‐jejunum. Jejunal varices were described as large prominent bluish vessels underneath visualized mucosa, one with evidence of recent bleeding. The results led to venoplasty of the portal vein in two patients and a decompressive shunt in one patient with resolution of GI bleed and anemia. CE is useful to diagnose intestinal varices in children with portal hypertension and GI bleeding following liver transplant.     

Bevacizumab treatment in multifocal lymphangioendotheliomatosis with thrombocytopenia

Multifocal lymphangioendotheliomatosis with thrombocytopenia (MLT) is a rare disorder characterized by a proliferation of cutaneous and gastrointestinal (GI) lesions that have characteristics of both lymphatic and vascular lesions. Thrombocytopenia is associated with this syndrome and is thought to represent platelet destruction within the lesions. The natural history is one of multiple, life‐threatening episodes of GI bleeding. We report the successful use of bevacizumab in this disease, an antibody to the vascular endothelial growth factor. Pediatr Blood Cancer 2009;52:534–536. © 2008 Wiley‐Liss, Inc.     

Embolization of congenital portosystemic shunt presenting after pediatric liver transplantation: Case report and literature review

This case report describes a 13‐year 10‐month‐old girl who underwent a deceased‐donor split LT for primary diagnosis of biliary atresia at the age of 12 months, who presented with a lower GI bleed. Ultrasound and CT revealed a venous vascular anomaly involving the cecum and ascending colon, with communication of the SMV and pelvic veins consistent with a CEPS. Associated varices were noted in the pelvis along the uterus and urinary bladder. These findings were confirmed by trans‐hepatic porto‐venography, which was diagnostic and therapeutic as a successful embolization of the CEPS was performed using micro‐coils. There were no complications following the procedure and no further GI bleeding occurred, illustrating the efficacy of this treatment option for CEPS. We discuss the literature regarding the presenting complaint of GI bleeding post–LT, CEPS as a rare cause of GI bleeding and its association with PV, and the classification and treatment of CEPS.     

Romiplostim treatment allows for platelet transfusion‐free liver transplantation in pediatric thrombocytopenic patient with primary sclerosing cholangitis

Thrombocytopenia is a major risk factor for cirrhotic liver disease. Patients with thrombocytopenia may have esophageal or gastric varices secondary to portal hypertension, leading to variceal bleeding which exposes the liver to further damage. Here, we present a female pediatric patient with PSC and CD, whose progressive thrombocytopenia was successfully controlled by romiplostim, a TPO receptor agonist. The patient developed bloody diarrhea at four yr of age, and was subsequently diagnosed with PSC and CD when seven yr old. While CD was well‐controlled by immunomodulators, the patient's thrombocytopenia gradually progressed resulting in petechiae (platelet count of 11 × 10⁹/L) when she was 10 yr and four months old. She responded poorly to immunoglobulin and corticosteroids. Weekly subcutaneous injection of romiplostim was therefore initiated, and platelet counts were maintained over at 50 × 10⁹/L. She was able to undergo successful LDLT without platelet transfusion seven months after the initiation of romiplostim. Romiplostim was not required after LDLT with improved platelet counts. This case report suggests that romiplostim may be effective in the treatment of thrombocytopenic children with liver cirrhosis and portal hypertension, and in eliminating the need for platelet transfusion during the peri‐transplant period.     

Blue rubber bleb nevus syndrome and gastrointestinal haemorrhage: which treatment?

PURPOSE: To describe a paediatric case of "Blue Rubber Bleb Nevus Syndrome" (BRBNS) or Bean's syndrome, a rare systemic disorder characterised by cutaneous and gastrointestinal vascular malformations that often lead to overt life-threatening gastrointestinal bleeding or occult blood loss with severe anaemia and iron deficiency. CASE REPORT: A 6-year-old girl with multiple characteristic cutaneous vascular lesions was admitted for a massive rectal bleeding. A few months previously she was endoscopically treated for gastric angiomas which developed into melaena. Preoperative investigations revealed the recurrence of gastric lesions. At laparotomy, more than 25 angiomas of the GI tract were found. Multiple intestinal resections were carried out. RESULTS: No intraoperative or postoperative problems occurred and the girl is completely healthy without further bleeding after a follow-up period of three years. CONCLUSIONS: BRBNS belongs to the group of vascular venous malformations. Most of the time it occurs sporadically, but it can be inherited as an autosomal dominant trait. Recent analysis identified a locus on chromosome 9 responsible for venous malformations. BRBNS patients present typical skin lesions, with some lesions having a rubber-like nipple appearance; the number of skin and GI lesions and the severity of anaemia are correlated. Treatment is dependent on the extent of gut involvement and the severity of the clinical picture. In the absence of massive bleeding, a conservative treatment will be sufficient; otherwise resections are mandatory, but additional lesions may subsequently develop. Management with electrocautery or laser photocoagulation are usually not effective even if some reports recommend them. Pharmacological treatment is useless. Prognosis of BRBNS is unknown.     

Hepatic angiosarcoma mimicking congenital cytomegalovirus infection in an infant with thrombocytopenia

Hepatic angiosarcomas are uncommon, highly aggressive tumors, rarely seen in children. A 3‐month‐old female infant was admitted to hospital for evaluation of multiple petechiae on her body. She had hepatosplenomegaly and scattered petechiae over her entire body. Laboratory tests indicated thrombocytopenia and positive cytomegalovirus (CMV) polymerase chain reaction. Ganciclovir was started, and the platelet count increased. After 4 months the patient was readmitted to hospital for drowsy mental status and eventually died from severe bleeding. Needle biopsy of the liver was performed after receiving written consent from the parents. Pathological findings of the liver lesion included features consistent with hepatic angiosarcoma. There have been no previous reports of hepatic angiosarcoma in Korean infants. Here, we report an infant with hepatosplenomegaly and thrombocytopenia who was diagnosed with hepatic angiosarcoma mimicking congenital CMV infection.     

Blue rubber bleb nevus syndrome

Blue Rubber Bleb Nevus Syndrome (BRBNS) is a rare condition characterized by multiple venous malformations involving the skin and internal organs. The gastrointestinal tract is always involved and intestinal haemorrhage is the most frequent clinical manifestation associated with iron deficiency anaemia. We describe a 10‐year‐old girl who, since birth, presented numerous venous malformations all over her body and a lymphangioma in the right leg. At the age of 5 years, she also had a severe episode of gastric bleeding requiring a blood transfusion. From this episode, she is suffering from chronic anaemia and this is the reason for admission into our hospital. The endoscopic examination of the gastrointestinal tract revealed multiple giant venous malformations in the oesophagus, stomach, duodenum and in all visible sections of the colon. Endoscopy is the gold standard technique for the diagnosis of BRBNS with GI lesions and also allows immediate therapeutic measures such as argon plasma coagulation, laser photocoagulation, sclerotherapy or band ligation. In addition, pharmacological treatments based on corticosteroids, interferon alfa, vincristine or octreotide have been described for BRBNS. Conclusion: Blue Rubber Bleb Nevus Syndrome is a congenital cutaneous and gastrointestinal haemangiomatosis. Its morbidity and mortality depends on involvement of visceral organs and particularly on GI bleeding. The treatment is based on pharmacological or surgical therapy. Overall, the most important step is the follow‐up to the presence and the evolution of GI lesions and the possible bleeding.     

Ibrutinib for the treatment of chronic graft‐vs‐host disease in pediatric hematopoietic stem cell transplant patients: A single‐center experience

cGVHD is a significant cause of morbidity and mortality after transplant. Ibrutinib has been studied as treatment for cGVHD in the adult population. Pediatric dosing and safety of ibrutinib are unknown. We conducted a retrospective review on the use of ibrutinib in 22 children with cGVHD at Cincinnati Children's Hospital Medical Center. All patients received a dose of 250 mg/m² orally, once daily. Responses were measured at 6 months after drug initiation using the 2014 NIH consensus panel response criteria. Twenty‐two patients of median age 13.5 years received ibrutinib. cGVHD grades were severe (n = 15), moderate (n = 6), and mild (n = 1). Eight patients stopped ibrutinib prior to 3 months due to adverse events or death and could not be evaluated for 6‐month response. Of the 14 evaluable patients, 12 achieved a partial response at 6 months and two patients had progressive disease. Seven evaluable patients with lung involvement had stable lung function at 6 months. One patient had EBV reactivation, and one patient developed pneumococcal sepsis despite appropriate prophylaxis while on ibrutinib therapy. No fungal infections occurred while on ibrutinib. Adverse events leading to discontinuation included recurrent fevers without a source, extensive bruising, oral bleeding, gastrointestinal distress, lower GI bleeding, dizziness, elevated transaminases, and pneumococcal sepsis. Ibrutinib administration of 250 mg/m² oral daily shows promising responses in pediatric cGVHD. Pediatric‐focused pharmacokinetic‐directed studies are needed to establish optimal dosing and define efficacy in children.     

Orthotopic liver transplantation for Sensenbrenner syndrome

Sensenbrenner syndrome, or cranioectodermal dysplasia, is a rare heterogeneic autosomal recessive disorder, affecting ~1 of 1 000 000 live births. The syndrome usually manifests within the first year of life and can present with progressive liver and renal involvement. For all Sensenbrenner patients, renal and liver diseases are the main contributors of morbidity and mortality. In this report, we present the case of a 7‐year‐old boy with congenital liver disease progressing to liver failure secondary to Sensenbrenner syndrome. For this patient, evidence of liver dysfunction was evident from 2 months of age and progressed to frank cirrhosis and severe portal hypertension with multiple episodes of life‐threatening variceal bleeding by age 6. This report illustrates the capability of orthotopic liver transplantation as a viable therapy for those pediatric patients suffering from severe liver failure secondary to a congenital ciliopathy, such as Sensenbrenner syndrome. In fact, early emphasis should be placed on the renal and liver involvement associated with Sensenbrenner syndrome with particular consideration for early referral for transplantation in cases with severe disease. Although the condition is rare, clinicians should be aware of it and its association with fatal liver disease to facilitate appropriate evaluation and referral.     

Pancreas‐preserving duodenectomy after living donor liver transplantation for invasive cytomegalovirus disease

CMV infection plays an important role in the postoperative course following solid organ transplantation. We present the case of an 11‐year‐old male patient who underwent LDLT due to severe hepatopulmonary syndrome and biliary cirrhosis. Four weeks after LDLT, he developed persistent GI bleeding and was subjected to repeated endoscopic treatment and radiological arterial embolization to stop the bleeding from duodenal ulcers. Diagnostic workup was negative for CMV disease. Because the bleeding persisted, surgical treatment was indicated, and a pancreas‐preserving duodenectomy was performed. Immunohistochemical staining of the surgical specimen demonstrated diffuse endothelial infiltration by CMV. Despite ganciclovir treatment, the patient developed new erosions in the jejunal mucosa and melena; ganciclovir was discontinued, and foscarnet was started, resulting in clinical improvement and the cessation of bleeding. This case highlights the technical aspects of performing a complex upper GI resection in a patient recently subjected to LDLT, taking care to avoid injury to the previous liver graft anastomosis and restore GI continuity. Moreover, CMV tissue‐invasive disease compartmentalized in the GI tract may be difficult to diagnose, as indicated by the negative results of antigenemia and PCR assays and endoscopic superficial mucosal biopsies.     

Out-of-reach obscure bleeding: single-balloon enteroscopy to diagnose and treat varices in hepaticojejunostomy after pediatric liver transplant

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.     

Management of intestinal bleeding with single‐dose cyclophosphamide in Henoch–Schönlein purpura

In these case series, we report on six children (3 girls, 3 boys) aged 5–13 years with Henoch–Schönlein purpura (HSP) who developed severe gastrointestinal (GI) bleeding resistant to both 2 mg/kg or pulse (10–30 mg/kg) i.v. methylprednisolone. All patients responded to single‐dose (500 mg/m²) i.v. cyclophosphamide (CPA) and none of them developed new GI bleeding after CPA treatment. No patients required surgical intervention. Single high‐dose CPA may be beneficial in HSP with severe GI involvement, in which bleeding is non‐responsive to high‐dose steroids.     

Recanalization of post‐transplant late‐onset long segmental portal vein thrombosis with bidirectional transhepatic and transmesenteric approach

PV complications are the most frequent vascular complications in pediatric LT. We have experienced a case with chronic postoperative PVT that necessitates combined transhepatic and transmesenteric approach and have confirmed mid‐term patency. An eight‐yr‐old boy had successful LDLT with a left lateral segment graft at the age of two months for HBV‐related acute liver failure. Seven years after transplantation, the patient suddenly showed a melena with hypovolemic shock. Doppler ultrasound and CT revealed intrahepatic bile duct dilatation and main PVT with collateral formation at hepatic hilus and mesenterium of the Roux‐en‐Y jejunal loop. Urgent splenic artery embolization was performed to control the bleeding and was temporarily effective. Therefore, recanalization of PVO was attempted. Because of long segmental PVO and steep angle between the intrahepatic PV and the portal trunk, bidirectional transhepatic and transmesenteric approach was selected and resulted in deploying three metallic stents necessitating additional infusion thrombolytic therapy. The patient is now followed as an outpatient with patent stents for two yr since the procedure. For the rescue of these patients, recanalization of obstructed PV trunk with bidirectional approach would be feasible with better graft survival and less invasiveness than conventional surgical interventions.     

Recurrent hepatosplenomegaly and peripheral blood cytopenia, persistent Epstein-Barr virus infection and central nervous system manifestation in a patient with lymphadenopathy and low serum uric acid

Abstract We describe a 27-month-old boy who was first admitted to our hospital on 7 January 1995 with nasal bleeding. From 6 months of age he has had lymphadenopathy, low levels of serum uric acid, increased levels of serum lactate dehydrogenase and hyper -y-globulinemia. From the age of 18 months he has had persistent Epstein-Barr virus (EBV) infection (target cells; B cells), recurrent episodes of thrombocytopenia, anemia and hepatosplenomegaly. Dysmobility of the left leg and arm from a central nervous system complication during a relapse with pancytopenia on March 1995, was also observed. Relapses of thrombocytopenia with increases of platelet-associated immunoglobulin G and hepatosplenomegaly have been observed approximately every 2 months, and two relapses of pancytopenia were accompanied with weak positivity of Coombs test and low level of haptoglobin. These recurrent episodes were improved with prednisolone. However, now in June 1997 we have not been able to diagnose what underlies the above clinical symptoms, except that the patient has a persistent EBV infection.     

Factors predicting persistent thrombocytopenia after living donor liver transplantation in pediatric patients

Thrombocytopenia is common after LT for pediatric end-stage liver diseases. Seventy-six pediatric patients (≤15 yr old) who underwent LDLT were evaluated for the incidence and predictive factors of post-transplant thrombocytopenia (PLT <100, 000/mm(3) ). The prevalence of thrombocytopenia at two wk and at 12 months post-transplant was 22/76 (28.9%) and 11/62 (17.7%), respectively. Thrombocytopenia at two wk after LDLT was significantly associated with age at transplant, preoperative PLT, GRWR, acute rejection, and CMV infection in univariate analysis. Moreover, preoperative PLT, GRWR, and acute rejection had a strong correlation in multivariate analysis. Thrombocytopenia at 12 months after LDLT was associated only with preoperative PLT. We also demonstrated that vascular complications caused thrombocytopenia and that successful treatment recovered the PLT. These results showed that, in addition to considering the preoperative PLT, post-operative monitoring of platelets is very helpful for the early detection of adverse events related to the graft liver in pediatric liver transplant patients.     

Management of intracranial hemorrhage in severe factor V deficiency and definitive treatment with liver transplantation

FV is primarily produced in the liver, and congenital FV deficiency is a disorder with an incidence of one in 1 million. Standard care is to treat severe bleeding phenotypes with FFP as there is no recombinant or plasma‐derived FV concentrate. We present a case of a neonate with known severe FV deficiency diagnosed after prolonged bleeding after circumcision who represented at age 2 months with a large left intraparenchymal hemorrhage. His bleed was treated with FFP, platelet transfusion, recombinant VIIa, and emergent evacuation. He was maintained on plasma infusions but was unable to space his infusions beyond 48 hours. Liver transplantation was considered as a definitive treatment for this condition. While awaiting a suitable liver, his FV trough levels occasionally dropped below 5%, and he suffered from a second acute intracranial bleed. He received an orthotopic liver transplant at age 5 months, resulting in correction of his FV levels. He has not required any plasma infusions post‐transplantation and has had no further bleeding episodes. Liver transplantation should be considered as definitive treatment early in the course for patients with severe FV deficiency and first time life‐threatening bleed.     

Long‐term follow‐up of de novo allergy in pediatric liver transplantation – 10 yr experience of a single center

We conducted a study to clarify the incidence, clinical course, and risk factors of de novo allergies after liver transplantation. Ninety‐three patients who had been followed longer than one yr and who had no previous allergy history were included. Forty‐two patients (45.2%) developed de novo allergy. Of them, food allergy developed in 35 (37.6%). Respiratory allergy was observed in three (3.2%), and a patient (1.1%) had drug allergy. Fifty‐two (55.9%) of the 93 patients developed eosinophilia. The median age of patients with de novo allergy was 15 months (IR 11.3–20 months). De novo allergy developed five months after liver transplantation (IR 2.3–9.5 months) and lasted for 16 months (IR 8–34.5 months). Younger age at liver transplantation displayed statistically significant differences in development of allergy between allergy and non‐allergy groups. Twenty‐nine (69.0%) patients improved from allergy during the follow‐up period. No patient with de novo gastrointestinal allergy progressed to any respiratory allergy such as asthma. Older age at transplantation, EBV non‐risk, and CMV non‐risk had statistical significance in allergy improvement. Younger age at transplant predisposes to the development of allergy, while improvement of allergy is achieved more in older age.     

A Case of Severe Thrombocytopenia Due to Parvovirus B19 Virus

A 9-year-old girl admitted with generalized skin, mucosa, and genitourinary system bleeding had anemia and thrombocytopenia. Her bone marrow was normocellular. Parvovirus B19 IgM and IgG were positive. An absence of reticulocytopenia suggested that the virus affected only the megakaryocytic cell line and the anemia was due to generalized bleeding resulting from thrombocytopenia. Intravenous immunoglobulin treatment was instituted. On the tenth day of hospitalization the patient recovered from anemia and thrombocytopenia. IgM antibodies disappeared.     

IVC angioplasty using an autologous vascular graft for IVC stenosis due to metallic stent in a pediatric liver transplant

A 12‐year‐old girl underwent LDLT using a left lobe graft for hepatic dysfunction associated with citrin deficiency. A continuous anastomosis suture technique was performed between the recipient's IVC and the donor's left hepatic vein. At age 14, the patient developed intractable ascites. Venography of the IVC and hepatic vein showed twisted‐shape stenosis of the hepatic vein‐IVC anastomosis with intravascular pressure gradient, probably due to the enlarged transplanted liver, for which a metallic stent was placed. The ascites disappeared, and the patient was making satisfactory progress eight months after surgery. However, nine months after surgery, the ascites appeared again with edema in the lower extremities. Since the stent that had been inserted was suspected of hampering the outflow of the graft liver and IVC, it was decided to conduct stent removal and IVC angioplasty. After intravascular exploration, the stent was removed. Angioplasty was performed. An autologous vascular graft patch was designed to be wedge‐shaped to fit the incised part of the IVC, and it was sutured with 5‐0 non‐absorbable surgical sutures using a continuous suture technique. No postoperative complications or perioperative graft dysfunction were observed. The ascites decreased markedly, and the edema in the lower extremities disappeared. Thus, we were able to successfully perform IVC angioplasty using an autologous vascular graft patch in a patient who developed IVC stenosis after stenting. This procedure is one of the most effective treatment options, especially for pediatric patients requiring long‐term vascular patency.