Castleman's disease of the mesentery in a child: A case of seven years' duration without typical x-ray findings

This report describes a 9-year-old boy with intermediate variant type of giant lymph node hyperplasia or Castleman's disease (CD) originating from the mesentery. He had symptoms and signs related to the disease for seven years before the final diagnosis. The patient's general condition remained good, except for periods of fever and abdominal pain. Pallor and slow growth were the only abnormal findings on physical examination during the follow-up. Laboratory measurements showed worsening microcylic anemia, low serum iron level, and low iron stores in bone marrow samples. The erythrocyte sedimentation rate (ESR) increased to 110 mm/h, and the serum levels of C-reactive protein varied between 80 and 120 mg/l. The level of serum albumin was low, 25–28 g/l, and serum immunoglobulin G was somewhat elevated, varying between 17–13 g/l. The radiologic examination of intestine gave pathological results suggesting a small bowel disease, but no tumor was detected. The abnormal laboratory values and symptoms of the patient resolved completely after surgical removal of the mass. Med. Pediatr. Oncol. 28:362–365, 1997. © 1997 Wiley-Liss, Inc.     

Heart transplantation in two adolescents with Danon disease

Danon disease (DD) is an X‐linked dominant disorder caused by a mutation in the lysosomal‐associated membrane protein‐2 (LAMP‐2) gene coding for the LAMP‐2 protein. We report two cases of successful heart transplantation (HT) in adolescent brothers with DD, including one who was bridged to HT for 34 days with a HeartWare left ventricular assist device. In both patients, the post‐transplant course was complicated by profound skeletal muscle weakness that resolved with corticosteroid withdrawal. These cases highlight that both HT and ventricular assist device support are feasible in patients with DD. Corticosteroid use may exacerbate skeletal myopathy, and therefore, steroid minimization may be warranted whenever possible.     

First reported use of the heartware HVAD in the US as bridge to transplant in an adolescent

D’Alessandro D, Forest SJ, Lamour J, Hsu D, Weinstein S, Goldstein D. First reported use of the heartware HVAD in the US as bridge to transplant in an adolescent. Abstract: Limited options exist for mechanical circulatory support as a bridge to transplantation in pediatric patients with advanced heart failure. This is particularly true when it comes to intracorporeal technologies. We describe the first reported experience with the use of the HVAD in the US as a successful bridge to transplantation in a 13‐yr‐old patient.     

Prognostic significance of tissue Doppler imaging–derived myocardial performance index in pediatric patients with dilated cardiomyopathy

TDI–MPI has been shown to predict cardiovascular mortality in adults; there are a paucity of data on its use in children. We sought to determine the prognostic significance of TDI‐MPI at time of DCM diagnosis in children. Patients aged ≤18 years diagnosed with DCM were included along with age‐ and sex‐matched controls. Echo at diagnosis was analyzed to obtain standard measures of LV function, PW‐MPI, and septal and LV free wall TDI‐MPI. Survival analysis was used to assess the time to composite outcome of death, VAD, or transplant, stratified by TDI‐MPI z‐score. The study included 79 patients with DCM and 79 controls. During a median follow‐up of 182 days (IQR 41‐815 days), 16 underwent VAD placement, 21 underwent cardiac transplant, 6 died, and 36 had event‐free survival. The median septal TDI‐MPI for cases was 0.70 for patients with DCM vs 0.45 for controls (P < .001). Those with septal TDI‐MPI z‐scores ≥2 develop events significantly earlier than those with z‐score <2 (P = .014). In multivariable analysis, TDI‐MPI z‐score ≥2 was significantly associated with poor outcomes (HR 2.12, 95% CI 1.06‐4.23). TDI‐MPI can be reliably performed in pediatric patients with DCM. A TDI‐MPI z‐score ≥2 at diagnosis may be associated with earlier poor outcome. Further studies evaluating the use of TDI‐MPI in longitudinal follow‐up of patients with DCM may be helpful in refining its clinical use.     

Extracorporeal membrane oxygenation (ECMO) for heart failure in children: a review of current practice

Mechanical circulatory support (MCS) is a valuable treatment modality for a small proportion of children with heart failure who are refractory to conventional medical management. Advances in MCS technology, particularly in recent times with the advent of ventricular assist devices (VADs) has made it possible to offer life support for this diverse population. ECMO has historically been used to provide temporary support for children with heart failure either as a bridge to recovery and occasionally as a bridge to heart transplantation, particularly in the pre-VAD era. In contemporary practice, ECMO may be used in refractory end-stage heart failure with end-organ dysfunction as a bridge to decision regarding transplant candidacy or as a bridge to a durable MCS device pending recovery of other end-organ dysfunction. The management of a child supported on ECMO is complex and requires multidisciplinary expertise. Ensuring optimal conditions for myocardial rest and recovery whilst mitigating for complications remains challenging. Cumulative experience has shown that although survival has improved there are a growing number of ECMO survivors in need of long-term follow-up. In this review, we will focus on children with systolic heart failure requiring ECMO as a form of MCS given the established role of VADs in paediatric heart failure.     

Basiliximab treatment for autoimmune bowel disease in a pediatric heart transplant patient

Autoimmune‐mediated bowel disease has been reported after pediatric heart transplantation. Recognition and treatment of these patients has been difficult. We describe a patient who responded to steroids and basiliximab therapy after an inflammatory process secondary to abnormal T‐cell activation. Our patient is a 28‐month‐old female who received a heart transplant at five wk of age. At 24 months post‐transplant, she developed fever and bloody stools. Initial investigations were significant for an elevated ESR (>120) and CRP (15.2). Symptoms persisted despite bowel rest and mycophenolate discontinuation. Endoscopic evaluation revealed discontinuous ulcerative disease involving esophagus, terminal ileum, right and left colon, necessitating extensive bowel resection. She had additional airway inflammation leading to a TEF at the site of esophageal ulceration, requiring tracheostomy. Immune evaluation revealed autoimmune dysregulation that responded to parenteral methylprednisolone. Chronic basiliximab therapy allowed for successful weaning of steroids with sustained remission. She has been transitioned to sirolimus and tacrolimus maintenance immunosuppression with plans to discontinue basiliximab once off steroids. In conclusion, bowel disease in the setting of pediatric heart transplantation can be severe and refractory to traditional treatment methods. Tailoring immune therapy to activated T cells can result in remission. Basiliximab therapy was used in our patient to maintain steroid‐induced remission, but long‐term complications of this disease process are unknown.     

Successful treatment of a classic Hodgkin lymphoma‐type post‐transplant lymphoproliferative disorder with tailored chemotherapy and Epstein–Barr virus‐specific cytotoxic T lymphocytes in a pediatric heart transplant recipient

CHL type is the least common major form of EBV‐related PTLD but rarely occurs in pediatric recipients; development of CHL subsequent to other PTLD subtypes in the same transplant recipient is even more unusual. Because of its rarity, indications on the best treatment strategy are limited. Patients have been mostly treated with standard HL chemotherapy/radiotherapy, and prognosis seems more favorable than other monomorphic PTLDs. Herein, we describe a pediatric case of EBV‐associated, stage IV‐B, CHL arising in a heart allograft recipient eight yr after diagnosis of B‐cell polymorphic PTLD. The patient was successfully treated with adjusted‐dose HL chemotherapy and autologous EBV‐specific CTL, without discontinuation of maintenance immunosuppression. At two yr from therapy completion, the patient is in CR with stable organ function. With this strategy, it may be possible to reproduce the good prognostic data reported for CHL‐type PTLD, with decreased risk of organ toxicity or rejection.     

Decline in ventricular function as a result of general anesthesia in pediatric heart transplant recipients

Echocardiography is frequently performed under anesthesia during procedures such as cardiac catheterization with EMB in pediatric HTx recipients. Anesthetic agents may depress ventricular function, resulting in concern for rejection. The aim of this study was to compare ventricular function as measured by echocardiography before and during GA in 17 pediatric HTx recipients. Nearly all markers of ventricular systolic function were significantly decreased under GA, including EF (?4.2% ±1.2, P < .01) and RV FAC (?0.05 ± 0.02, P = .04). Subjects in the first post‐transplant year (n = 9) trended toward a more significant decrease in EF vs those beyond the first post‐transplant year (n = 8; ?6.0% ±1.2 vs ?2.1 ± 2.0, P = .1). This information quantifies a decline in biventricular function that should be expected in pediatric HTx recipients while under GA and can assist the transplant clinician in avoiding unnecessary treatment of transient GA‐induced ventricular dysfunction.     

Case-control study of risk factors for the development of post-transplant lymphoproliferative disease in a pediatric heart transplant cohort

PTLD is an important complication following heart transplantation. To better define the risk factors of PTLD in children, we performed a case-control study. All pediatric cardiac transplant recipients who developed their first episode of PTLD were matched by age (+/-1 yr) and time since transplant (+/-1 yr) with those who did not. PTLD occurred in nine of 95 cardiac transplant recipients (9%), 0.3-7.8 yr following cardiac transplantation (median = 2.5 yr). Patients were 0.1-16.4 yr (median = 3.7) at transplantation. Biopsies revealed polymorphic B cell hyperplasia (three), polymorphic B cell lymphoma (one), monomorphic diffuse large cell B cell lymphoma (three) and monomorphic Burkitt's-like lymphoma (two). Patients who developed PTLD were at no greater risk of death (p = 0.31). Recipient EBV seronegativity at time of transplant (p = 0.08), EBV seroconversion (p = 0.013) and recipient CMV seronegativity (p = 0.015) were associated with the development of PTLD by conditional logistic regression; sex, race, donor age, recipient diagnosis, donor CMV seropositivity, recipient treatment for CMV infection, EBV seropositivity at the time of PTLD diagnosis, and number of rejection episodes, treated rejection episodes, and lympholytics used were not. There was no significant association between PTLD and death in our recipients. EBV seroconversion and recipient CMV seronegativity were associated with the development of PTLD.     

Basiliximab therapy for immune-mediated bowel disease in a pediatric heart transplant patient

In pediatric patients who undergo heart transplantation, severe immune-mediated bowel disease has been reported. Management is complex, and there are little data discussing the use of basiliximab for immune-mediated bowel disease. This case report discusses a pediatric patient who developed immune-mediated bowel disease following heart transplantation and was successfully managed with basiliximab.     

Optical coherence tomography for the evaluation of asymmetric cardiac allograft vasculopathy in a child

We present an unusual case of CAV in a child with isolated disease in the LAD coronary artery. Initial progression of the disease appeared to have been halted by the use of sirolimus, but the assessment of disease in other vessels (particularly the RCA) was of particular importance in deciding whether or not to relist this patient for transplantation. Due to the known limitations of coronary angiography, we used OCT to assess for angiographically silent CAV. The normal intravascular appearance of the RCA by OCT was reassuring, and the child was not relisted for transplantation. OCT offers multiple advantages for the assessment of CAV in children.     

Restrictive hemodynamics are present at the time of diagnosis of allograft coronary artery disease in children

Clinical recognition of allograft coronary artery disease (ACAD) is challenging. We examined whether right heart hemodynamics can aid its diagnosis in pediatric recipients. We retrospective analyzed hemodynamic data of recipients with ACAD versus age and date-of-transplant matched controls. From 1982-2001, 18 cases fulfilled study entry criteria. Median age at transplant was 12 years for subjects and 8 years for controls. Median time to diagnosis of ACAD was 65 months (14.5-124 months) and 67 months (16-140 months) to arteriography for controls. The median right ventricular end-diastolic pressure (RVEDP) at diagnosis was 11.0 vs. 6.0 mmHg for controls (p = 0.003). Pulmonary capillary wedge pressure (PCWP) at diagnosis was 14.0 vs. 8.0 mmHg for controls (p = 0.001). When subdivided by severity of ACAD, the difference was greater in the moderate/severe group. Compared to the previous catheterization (median interval 10 months for subjects, 12.0 for controls ), there was an increase of 4.0 mmHg in RVEDP in ACAD subjects (n = 13, p = .003) versus 0 mmHg in controls (p = 0.042), and an increase in PCWP of 5.5 in subjects (p = .002) versus 0 mmHg in controls (p = 0.066). The presence of elevated filling pressures plus an interim increase should alert to the presence of ACAD and help guide further investigation.     

Veno-occlusive disease of the liver in a child after chemotherapy for brain tumor

Veno-occlusive disease (VOD) of the liver is a life-threatening state generally occurring as a complication of bone marrow transplantation or chemotherapy for Wilms' tumor. Veno-occlusive disease after standard dose chemotherapy in malignancies other than Wilms' tumor is rare and only a few cases have been published in children. We report a 19 month-old-girl with medulloblastoma who experienced fatal VOD of liver after only one course of chemotherapy including carboplatin, vincristine and CCNU for medulloblastoma. As our knowledge, this is the first report of VOD after standard dose chemotherapy for brain tumor in childhood.     

The profile of renal function over time in a cohort of pediatric heart transplant recipients

Abstract:  To assess the burden over time of renal dysfunction in pediatric heart transplant patients using an objective measure on an annual basis for serial comparison. GFR was measured at regular interval by nuclear medicine scintigraphy. Results were analyzed in relation to age, time post-transplantation, gender, and average calcineurin-inhibitor dose for the first two months post-transplantation. Results were compared with cGFR using the Schwartz equation. A total of 91 patients (56 males) transplanted between 1990 and 2004 underwent 373 GFR measurements. Median age at transplantation was 3.3 yr (birth – 17.8). Median first GFR at 0.7 yr (0.1–4.1) post-transplant was normal (94 mL/kg/1.73 m²). Freedom from at least mild renal insufficiency was 84% and 33% at one and five years post-transplant. Females had better renal function early post-transplant (GFR 105 mL/min/1.73 m²) but an increased probability of an abnormal GFR over time. Higher calcineurin inhibitor dose in the first two months post-transplantation was associated with an increasing probability of an abnormal GFR over time. The cGFR overestimated the measured GFR by 33 ± 26 mL/kg/1.73 m². Renal insufficiency is an important morbidity after pediatric transplantation with the majority of patients experiencing at least mild renal dysfunction. Calculated GFR significantly underestimates the burden of renal insufficiency in this patient population.     

Treatment of Hodgkin's disease in children with alternating mechlorethamine,vincristine, procarbazine,and prednisone (MOPP) and adriamycin,bleomycin, vinblastine,and dacarbazine (ABVD) courses without radiotherapy

Since the introduction of mechlorethamine, vincristine, procarbazine, and prednisone (MOPP) chemotherapy, children with Hodgkin's disease (HD) have been treated with chemotherapy alone. The occurrence of side effects related to irradiation (especially secondary solid tumors) is less likely to occur. Alkylating agents in the MOPP chemotherapy combinations are, however, known for their late effects, i.e., gonadal dysfunction and secondary malignancies. Combination with non-alkylating and non-cross-resistant drugs (as in the adriamycin, bleomycin, vinblastine, and dacarbazine [ABVD] combination) may give superior treatment results and possibly a decrease in the occurrence of side effects. From 1988 to 1993 all children presenting with HD were treated with alternating MOPP and ABVD courses (3 × MOPP, 3× ABVD). Twenty-one children (7 females, 14 males), ages 5–18 years (median 14 years) were included; their clinical stages were 1, 7 patients; II, 8 patients; III, 5 patients; IV, 1 patient. Their pathology revealed 2 lymphocytic predominance, 17 nodular sclerosis, 1 mixed cellularity. In 1 patient only cytology was done and thus histopathologic subclassification was not possible. Two children have relapsed; disease-free survival is 90%. Analysis of toxicity revealed no decrease in cardiac function by ultrasound examination and no pulmonary effects noted by carbon monoxide diffusion. In 1 of the 10 children tested, mild hypogonadism was noted. No secondary tumors occurred. From this small population of children with HD we conclude that treatment with MOPP/ABVD for 6 cycles without radiotherapy may be adequate. The occurrence of gonadal dysfunction may be less frequent than with 6 cycles of MOPP. However, more patients and further follow-up are needed. Med. Pediatr. Oncol. 29:23–27, 1997. © 1997 Wiley-Liss, Inc.     

Zoledronic acid for the treatment of osteopenia in pediatric Crohn's disease

Background: Pediatric patients with Crohn's disease often have low bone mass (osteopenia) for age. No randomized, placebo‐controlled trials using zoledronic acid have ever been performed in this population. The objective of this study was to assess the efficacy of zoledronic acid in children with Crohn's disease and osteopenia. Methods: A double‐blind, randomized, placebo‐controlled design was used. Thirteen adolescents received either a single intravenous dose of zoledronic acid (0.066 mg/kg, max 4 mg, n= 7) or saline placebo (n= 6). The primary outcome was change in lumbar spine bone mineral density (LSBMD) z‐score at 6 months. Secondary outcomes included bone markers and adverse events. Results: At 6 months, the change in LSBMD z‐score was significantly higher in the zoledronic acid group compared to placebo (0.7 vs 0.1, P < 0.001). Volumetrically adjusted LSBMD z‐score also significantly increased in the treated group. This significant difference persisted until 12 months. With zoledronic acid, urinary C‐telopeptide excretion decreased by 50% at 6 months and remained suppressed at 12 months (P= 0.02), but no changes were observed with placebo. Both groups had similar adverse events which included transient fever, arthralgias, and nausea (3/7 treated, 2/6 placebo, P= NS). Conclusions: In this study, zoledronic acid demonstrated a significant increase in LSBMD at 6 and 12 months following a well‐tolerated infusion.