Gastric angiodysplasia in a child with Bernard-Soulier syndrome: efficacy of octreotide in long-term management

Gastrointestinal angiodysplasia in association with Bernard-Soulier syndrome has been previously described in adults. The authors report on a 14-year-old boy presenting with massive upper gastrointestinal bleeding due to a large gastric angiodysplasia, in whom medical history and laboratory investigations were consistent with Bernard-Soulier syndrome. The vascular lesion was so widespread that surgical or endoscopic therapy was not considered. Therefore, treatment with octreotide, a somatostatin analog, was commenced, following a short course of tranexamic acid and proton pump inhibitor. During the 16-month follow-up with octreotide therapy, no occult or gross bleeding occurred. This case illustrates the utility of using octreotide for the long-term treatment of children with bleeding disorders and angiodysplasia.     

The German Society of Pediatric Oncology Cooperative Ewing Sarcoma Studies CESS 81/86: report after 6 1/2 years

The GPO Cooperative Ewing's Sarcoma Study (CESS 81 with 10 months four-drug combination chemotherapy (vincristine, actinomycin D, cyclophosphamide, and adriamycin = VACA) and local control with surgery and/or radiation, following week 18, resulted in a Kaplan-Meier estimated disease-free survival of 51% after 6 1/2 years (51/93 patients disease-free). Tumor volume and histological response to primary chemotherapy were identified as most significant prognostic factors. As a consequence, the CESS 86 regimen was stratified according to risk of relapse. Standard risk patients (extremity tumors less than 100 ml tumor volume) were continued on VACA chemotherapy. In high risk patients (extremity tumors greater than 100 ml tumor volume, central tumors), cyclophosphamide in conventional dose (1200 mg/m2/course) was replaced by high doses of ifosfamide (6 g/m2/course) with mesna uroprotection (VAIA). Local control was obtained following week 9. Patients with radiation were randomised for conventional fractionation or accelerated split-course hyperfractionation. The study was piloted from February to December 1985: 27/37 patients were disease-free on October 1, 1987. The ongoing trial was started on January 1, 1986. On October 1, 1987. 63/66 patients were disease-free. In patients with large primaries, according to Kaplan-Meier life-table analysis, the disease-free survival was significantly better in patients receiving VAIA chemotherapy, compared to the previous VACA regimen. The toxicity of both combination chemotherapy regimens was comparable.     

The clinical course of immune thrombocytopenic purpura in children who did not receive intravenous immunoglobulins or sustained prednisone treatment

OBJECTIVE: To demonstrate the result of watchful waiting without specific therapy in unselected children with acute immune thrombocytopenic purpura (ITP). STUDY DESIGN: Between May 1992 and October 1999, 55 consecutive children (aged 2 months to 16 years; 28 boys and 27 girls) with acute ITP did not receive intravenously administered immune globulin G (IVIG) or sustained prednisone treatment. Patients with extensive mucosal bleeding were given prednisone, 2 mg/kg/d, for 3 days. RESULTS: In 37 of 55 patients the initial platelet count was <10,000/microL. Ten of these patients had active mucosal bleeding. Five additional patients with bleeding had platelet counts between 10,000 and 20,000/microL. Four patients were given a 3-day course of prednisone. Chronic ITP occurred in 7 (13%) of the patients; 29 patients achieved remission within 6 weeks, and 19 patients, between 6 weeks and 6 months. No life-threatening bleeding occurred, and no patient died. CONCLUSION: Most children with severe thrombocytopenia do not have active mucosal bleeding. This management approach, which did not administer specific therapy, avoided side effects, reduced cost, and was effective.     

Chronic childhood idiopathic thrombocytopenia purpura: long-term follow-up

An understanding of the natural history of childhood chronic idiopathic thrombocytopenia purpura (ITP) could contribute to a rational therapeutic approach to its treatment, which remains controversial. In our retrospective study of 92 children with ITP, 22 had a chronic course and were followed for 3–14 years (median 8.6 years). Treatment, when indicated, was individualized: 4 patients (18.2%) did not receive any treatment, 14 (63.6%) received steroids only, while 4 (18.2%) were treated with steroids and one of the following: high-dose gamma globulin (4 patients), splenectomy (2 patients) or immunosuppressive therapy (2 patients). During follow-up, 14 patients (63.6%) achieved complete remission, 5 (22.7%) partial remission and only 3 (13.5%) remained severely thrombocytopenic, with minimal bleeding tendency. Eleven patients (50%) responded to the initial prednisone course (1–5mg/kg/day), but showed a marked decrease in platelet count when steroids were tapered off. In view of the high rates of complete and partial remission and the mild course of the few non-responding patients, it is suggested that with adequate supportive therapy, follow-up problems and fatalities can be kept to a minimum. We believe that aggressive therapy, such as splenectomy, should be reserved for the rare symptomatic and severely thrombocytopenic patient.     

Endoscopic ethanol injection for treatment of bleeding peptic ulcer

We treated three children aged 10, 11 and 13 years with actively bleeding ulcers using local endoscopic injection of pure ethanol. Ethanol was injected into several sites around a visible vessel with or without bleeding. Haemostasis following ethanol injection therapy was confirmed by endoscopy performed the day after treatment. No rebleeding was observed. There were no complications related to the procedure. Injection therapy is technically simple and inexpensive.Conclusion Our results suggest that endoscopic ethanol injection is safe and may be the treatment of choice for control of bleeding from peptic ulcers in children.     

Prolonged activation of hypothalamo-pituitary-ovarian axis during early infancy in female patients with salt-losing 21-hydroxylase deficiency

We observed prolonged genital bleeding during the first 2-3 months after treatment in five of 13 female patients with salt-losing 21-hydroxylase deficiency. Their relatively low concentrations of serum follicle-stimulating hormone and luteinizing hormone before therapy increased rapidly to high levels which were maintained for 1-3 wk and then decreased. The duration of these relatively high levels after therapy was longer in the patients with genital bleeding than those without. Before therapy, there was no release of serum follicle-stimulating hormone and luteinizing hormone following the administration of synthetic luteinizing hormone-releasing hormone in two patients; 1 month after therapy, the response to luteinizing hormone-releasing hormone increased significantly. Serum estradiol increased above 300 pg/ml in four patients with genital bleeding but was less than 175 pg/ml in three patients without bleeding. The etiology of genital bleeding in these female patients may be more prolonged activation of the hypothalamo-pituitary-ovarian axis and a greater increase in the responsiveness of internal genitalia to gonadotropins and sex hormones, perhaps induced by prolonged exposure to excessive adrenal steroids starting before birth.     

Upper gastrointestinal bleeding in children and adolescents.

This is a retrospective study of upper gastrointestinal hemorrhage in 68 children and adolescents who were less than 19 years old. In descending order of frequency, the five most common causes were duodenal ulcers, gastric ulcers, esophagitis, gastritis, and esophageal varices. There was male predominance in all diagnoses except gastric ulcers and gastritis. Signs and symptoms correlated poorly with the source of bleeding. Endoscopy was the most reliable method of identifying the bleeding site. Mortality correlated with the following: (1) initial hematocrit or hemoglobin level of less than 20% or less than 7 gm/100 ml, respectively, (2) transfusion requirements of greater than 85 ml/kg of blood without surgical intervention, (3) failure to identify the source of bleeding, (4) presence of a coagulation disorder, and (5) coexistence of another life-threatening disease.     

Indomethacin treatment for symptomatic patent ductus arteriosus: a double-blind control study

A double-blind control study was designed to determine the efficacy and safety of indomethacin treatment of patients with symptomatic patent ductus arteriosus. Infants with severe respiratory distress syndrome and symptomatic patent ductus arteriosus were eligible for the prospective study if the ratio of left atrial/aortic root diameter remained greater than or equal to 1.3:1 following a 24-hour period of medical management. Thirty-nine eligible infants were randomly assigned to the control or indomethacin group and given 0.2 mg/kg of enteral indomethacin or placebo in a double-blind manner. Second and third doses were administered at 24-hour intervals in phase 1 (17 patients), and at eight-hour intervals in phase 2 (22 patients). The 75% patent ductus arteriosus closure rate with indomethacin treatment in phase 1 was not statistically significant due to a 44% spontaneous closure rate in the control group. In phase 2, however, 85% of the indomethacin group demonstrated patent ductus arteriosus closure vs only 11% in the matched control group (P less than .01). Although no indomethacin side effects occurred in phase 1, in phase 2 indomethacin administration was associated with minimal, but statistically significant, transient impaired renal function and, in three infants (23%), mild upper gastrointestinal bleeding. In summary, enteral administration of three 0.2 mg/kg indomethacin doses at eight-hour intervals thus appears to be a safe and effective alternative to surgical closure.     

Chronic vulvovaginitis caused by antibiotic-resistant Shigella flexneri in a prepubertal child

A 7-year 8-month-old girl was diagnosed with a prolonged course of vulvovaginitis caused by Shigella flexneri. The child was symptomatic with intermittent vaginal bleeding, dysuria and foul smelling vaginal discharge for a 3-year period. Initial attempts to resolve the infection with successive courses of antibiotic therapy using ampicillin, trimethoprim-sulfamethoxazole, cefixime and amoxicillin/clavulanic acid failed. The child's infection was finally resolved by a 14-day course of ciprofloxacin.     

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.     

Use of activated factor VII in severe acute hemorrhage

Acute hemorrhage is a sometimes serious complication that may arise in patients admitted to the intensive care unit with coagulopathy. The usual therapy is transfusion of blood components: fresh frozen plasma, platelets, fibrinogen, red cell concentrate and vitamin K. Tolerance or response can sometimes be poor. We present three patients aged 18 months, 4.5 and 10 years who suffered an acute episode of severe, life-threatening hemorrhage in the course of meningococcal sepsis (gastric hemorrhage), myelomonocytic leukemia (during splenectomy) and in the postoperative period after cardiovascular surgery. Traditional therapy was ineffective and activated factor VII was administered at doses of 50-70 microg/kg, with rapid control of bleeding.     

Surgical intervention in children with portal hypertension

Over a 5-year period 252 children with bleeding oesophageal varices secondary to portal hypertension were treated by endoscopic injection scletherapy. Surgical treatment was restricted to patients with bleeding complications following sclerotherapy and the occasional problem of symptomatic splenomegaly (2 children). Sclerotherapy failure was due to the development of varices not accessible to sclerotherapy (gastric fundus 7, duodenum 1, jejunum 1, unidentified site in small bowel 1) and to continued bleeding from oesophageal ulcers in 2 children. There were 5 children with Child's grade A cirrhosis. Fifteen children (4.4 % of the total; median age 8.7 years, range 1.5 – 18 years) underwent 16 operations during this period, which included 13 porto-systemic shunts (8 lieno-renal and 5 meso-caval) and 3 oesophageal transections/devascularisations. Sclerotherapy was not attempted in 1 of the 2 children treated for continued bleeding from oesophageal varices. Two lieno-renal shunts thrombosed and 1 of these patients underwent a meso-caval shunt. There were no deaths in this group of patients during a median follow-up of 40 months. One child with biliary atresia has developed a mild intermittent encephalopathy. The use of injection sclerotherapy for bleeding oesophageal varices with surgical intervention limited to patients failing treatment resulted in low morbidity and no mortality in a large group of children with portal hypertension. Correspondence to: N. D. Heaton     

Low molecular weight heparin for neonatal thrombosis

The clinical course of a term neonate (birthweight 3.14 kg) who developed thrombosis of the left common and internal iliac veins on day 21 following recovery from Streptococcus mitis septicemia, with shock diagnosed on day 13, is reported. Subcutaneous low molecular weight heparin (LMWH) was commenced (1.5 mg/kg 12 hourly for 10 days) after 13 h of standard heparin infusion, due to difficulties in securing a peripheral venous access. The inflammation of the left leg was completely resolved by day 5 of LMWH therapy. Prothrombin time, activated prothrombin time and fibrinogen levels were within normal limits during LMWH therapy. Treatment-related side effects, such as thrombocytopenia and bleeding tendency were not noted. Doppler studies 6 weeks after discharge home on day 33 revealed complete resolution of the thrombus. Apart from septicaemia and shock, the presence of an indwelling central venous catheter and a history of untreated maternal diabetes were additional risk factors for thrombosis. Because it is as effective as standard heparin, LMWH may be a therapeutic option for thrombosis in high-risk neonates, particularly given its ease of administration by the subcutaneous route, predictable pharmacokinetics and reduced incidence of adverse effects such as bleeding complications.     

Long‐term outcomes of de novo autoimmune hepatitis in pediatric liver transplant recipients

The long‐term course and outcome of DAIH is unknown. A retrospective multicenter study assessing associations and long‐term consequences of DAIH developing in a transplanted allograft is presented. Children with DAIH were followed from diagnosis until death, re‐LT, or transfer of care and for a minimum of 1 year. A total of 31 patients of 1833 (1.7%) LT were identified; 29 followed for a median of 7.1 years (range, 1.6‐15); 52% had no rejection preceding diagnosis of DAIH. Transaminases fell following treatment with steroids and antimetabolites (ALT 108 vs 39 U/L (P=.002); AST 112 vs 52 U/L (P=.003); GGT 72 vs 36 U/L (P=.03), but this was not universally sustained. Transaminases >2X ULN observed in 38% of patients at last follow‐up; commonly GGT, attributed to bile duct injury and ductopenia. Portal hypertension (PHT) was seen in four patients and associated with severe fibrosis and cirrhosis. Re‐LT occurred in two patients for chronic rejection (CR) and uncontrolled PHT with gastrointestinal bleeding, respectively. No deaths from DAIH were reported. DAIH is an uncommon complication following pediatric LT requiring prolonged and augmented immunosuppression. It is associated with continued allograft dysfunction and may lead to bile duct injury, CR, and PHT necessitating re‐LT.     

Characterizing adolescents with heavy menstrual bleeding and generalized joint hypermobility

Patients with generalized joint hypermobility (JHM) may experience excessive bruising/bleeding, with heavy menstrual bleeding (HMB) commonly reported. We performed a retrospective review of 30 adolescents seen in a Young Women's Hematology Clinic with both HMB and JHM. We found that (1) a significant delay (mean 36 months, range 5–72) occurred between menarche and referral to specialty care, (2) HMB had moderate to severe impact on school and physical activities in 60% of patients, and (3) most patients (68%) required escalation of their initial therapy. We suggest providers consider JHM as a risk factor for a more complex clinical course.     

Prolonged bleeding time in preterm infants receiving indomethacin for patent ductus arteriosus

Sequential bleeding times were performed on 25 preterm infants receiving intravenous indomethacin for closure of the patent ductus arteriosus. Prolongation of bleeding time was observed after the initial dose of indomethacin, with an increase from a pretreatment mean of 3.6 minutes to 8.7 minutes. The bleeding time was not further prolonged at the end of the three-dose course of indomethacin, but was still elevated 48 hours after the completion of therapy. Clinical bleeding developed in six of the patients, but was generally limited to occult hematuria. Serial echoencephalography during indomethacin therapy showed progression from mild periventricular-intraventricular hemorrhage to moderate or severe grades in five of 21 infants at risk for this complication. However, no clear temporal relationship between indomethacin administration and intraventricular hemorrhage extension was observed, and no difference in the degree of bleeding time prolongation was noted between infants with and without hemorrhage extension. Other factors, including surfactant deficiency, amount of volume expansion used, and lowest PO2 in the first day of life, did distinguish those with hemorrhage extension. The results suggest that indomethacin-induced platelet dysfunction is not associated with major hemorrhagic complications in the majority of preterm infants with patent ductus arteriosus.     

Carboplatin in childhood Medulloblastoma/PNET: Feasibility of an in vivo sensitivity test in an “up-front” study

Sixteen patients with high risk MB/PNET at diagnosis were included in a pilot study employing carboplatin (CBDCA) as a single drug prior to conventional therapy. The main goal of the study was to identify in a short-term trial a significant response that would predict further response to CBDCA in the single patient. Exploration of CBDCA activity was focused on response after the first course as compared to the response following the second course. A course consisted of CBDCA 600 mg/m² on days 1 and 2 administered in a 1 h infusion to be repeated 3–4 weeks later. After two cycles we observed 1 CR and 9 PR, that is a 62% response rate. The first course resulted in 5 PR, 5 MR, 5 SD, and 1 PD; after the subsequent course in all responding patients, response persisted or improved whereas in no patient with SD any improvement was observed. The correlation of response to the first course with response to the second course was statistically significant (P = 0.0009). The main toxicity of the single course was hematologic and consisted of rapidly reversible grade 3–4 neutropenia and thrombocytopenia in 94% of patients. Pharmacokinetic studies showed a very limited interpatient variability of both Cmax (57.6 ± 9.9 μg/ml) and AUC (15.3 ± 1.5 mg/ml · min) of free CBDCA, which eliminates an important variable in the evaluation of response. In conclusion, this “in vivo test” appears effective, reasonably safe, and reproducible in identifying patients likely to benefit from CBCDA: after a period of time as short as 3–4 weeks following the first course, multidrug chemotherapy including CBDCA may be employed in the responding patients, whereas an alternative regimen would be indicated in the non-responding patients. © 1995 Wi1ey-Liss Inc.     

纤溶酶原激活物抑制因子1基因多态性与过敏性紫癜胃肠道出血的相关性

目的研究纤溶酶原激活物抑制因子1(PAI-1)基因启动子区单核苷酸多态位点(4G/5G)和血浆PAI-1水平与过敏性紫癜(HSP)胃肠道出血的相关性。方法入选HSP急性期患儿524例,按是否有消化道出血分为消化道出血组(出血组,186例)和非消化道出血组(对照组,338例),比较分析两组患儿PAI-1基因型、PAI-1血清水平以及其他和凝血纤维溶解相关的指标。结果出血组患儿的血小板计数(PLT)、血小板分布宽度(PDW)、血清D-二聚体(DD)、血清PAI-1水平均高于对照组,而平均血小板体积(MPV)和血浆纤维蛋白原(FIB)水平低于对照组,差异均有统计学意义(P??0.05);出血组患儿的4G/4G基因型频率较对照组高,差异有统计学意义(P=0.04)。4G/4G基因型的血浆PAI-1水平、DD水平高。结论 PAI-1 4G/5G基因多态性可能通过影响血浆PAI-1表达水平以及凝血纤溶等因素而影响过敏性紫癜消化道出血的病理过程。     

Steroid treatment of idiopathic thrombocytopenic purpura in children. Preliminary results of a randomized cooperative study

Preliminary data from a prospective randomized study of the use of a short course of adrenocorticosteroids in 73 children with ITP demonstrates a significant advantage of moderate dose (60 mg/m2/day p.o. X 21 days) prednisolone therapy in decreasing the duration of severe thrombocytopenia in most patients. The period of risk for serious bleeding, as reflected in the Rumpel-Leede test, was also significantly reduced. The number of children who developed chronic thrombocytopenia, although small in both groups, appeared to be uninfluenced by steroid therapy. No side effects or serious complications were noted in this trial.