Intestinal parasites in children with neoplasms

Stool specimens taken from 50 children with malignancy and from 92 healthy children were investigated for intestinal parasites, using the modified formol ethyl acetate concentration method, and native-lugol, trichrome and Kinyoun acid-fast stain methods. Thirty-eight (76.0%) of the 50 patients had lymphoma or leukemia and were considered immunosuppressed. Several different parasites were found in 21 (42.0%) of the 50 patients with malignancy and in 16 (47.3%) of the 38 patients with immune deficiency compared to in only 16 (17.3%) of the 92 healthy children. The incidence of parasites in patients with malignancy or immunosuppression was significantly higher than in the healthy control group (p<0.01, p<0.01).     

Second primary tumors in children and young adults in the North of England (1968-99)

BACKGROUND: This study describes the risk of second malignancy in patients diagnosed with cancer under the age of 25 years, registered on the Northern Region Young Person's Malignant Disease Registry. PROCEDURE: Incidence rates were calculated to describe the occurrence of second malignancies, rate ratios were estimated to compare rates between subgroups. Standardized incidence ratios (SIRs) were calculated for comparison with a reference population. RESULTS: There were 4,072 children and young adults diagnosed with a first malignancy from 1968 to 1999, of whom 68 had a second malignancy (including basal cell carcinomas and meningiomas). The incidence rate of second malignancy is 1.7 per 1,000 survivor person-years (95% CI: 1.4, 2.2), reflecting a four-fold increased risk of malignancy compared with the general population. The rate of second malignancy was non-significantly higher for those diagnosed during young adulthood rather than childhood (RR = 1.2, 95% CI: 0.7, 2.0), significantly higher in females than males (RR = 1.8, 95% CI: 1.1, 3.0) and significantly lower for those diagnosed in more recent years (RR = 0.4, 95% CI: 0.2, 0.8). In contrast, the SIRs indicated that children were at substantial increased risk; whilst males and females, and those diagnosed in earlier and later time periods, were at equivalent risks. CONCLUSIONS: There is evidence of a sustained increased risk of second malignancy in those treated for primary cancer, especially those diagnosed in childhood; with no evidence that this risk is reducing.     

Bullous herpes zoster in a child with leukemia: case report and review of the literature

Blistering disorders in childhood are usually difficult to diagnose and pose complicated management dilemmas. The incidence of herpes zoster in children with malignancy and immunodeficiency is greatly increased compared to normal children of comparable age. Although herpes zoster is known to occur in children with malignancy, the bullous form of herpes zoster is rare; to the authors' knowledge, there was no previous report of this phenomenon in children in general and in children with cancer in particular. The authors describe a 3.5-year-old girl who was diagnosed with acute lymphoblastic leukemia; 7 months after presentation, during chemotherapy treatment, she developed the bullous form of herpes zoster on her right hand. The authors describe the method of diagnosis and provide a review of the literature concerning this rare phenomenon. Recognizing this entity and differentiating it from other bullomatous conditions enable the application of appropriate treatment, without unnecessary delay.     

Outcome of heart transplantation in pediatric cancer survivors

The aim of this study is to evaluate the outcome of heart transplantation in children surviving malignancies. Pediatric heart transplant recipients were identified using the UNOS database. Follow‐up data including survival and rate of malignancy were analyzed. A total of 7169 children received heart transplants between 1987 and 2011. Of these, 107 (1.5%) survived previous malignancy treatment (group I) and 7062 (98.5%) did not have prior malignancy (group II). Survival after transplant was 92.5%, 90.6%, 80.3%, and 65% at three months, one, five, and 10 yr in group I, similar to the rate in group II (90.1%, 84.4%, 73.8%, and 57.7%). Survival after transplantation was similar between group I and children who underwent OHT secondary to cardiomyopathy in group II. The rate of post‐OHT malignancy in group I was higher than that in group II (14/107(13%) vs. 386/7062 (5.4%), p = 0.001). Children who developed malignancy in group I had similar survival as children who developed malignancy in group II. Post‐transplant survival is similar in children with and without pretransplant malignancy in spite of higher rate of malignancy in children with pretransplant malignancy. OHT appears to be a reasonable treatment option in children who develop end‐stage heart disease after malignancy treatment.     

Calcified pulmonary thromboembolism in a child with sickle cell disease: value of multidetector CT in patients with acute chest syndrome

The incidence of pulmonary embolism in children is not clearly known, but is believed to be low. Risk factors for pulmonary thromboembolism include central venous catheter, malignancy, surgery, infection, trauma, and congenital hypercoagulable disorders. Children with sickle cell disease are prothrombotic and are at an increased risk of thromboembolism. The incidence of this event is unknown because these children are often not thoroughly imaged. We report here a case of a calcified pulmonary thromboembolism in a child with sickle cell disease and emphasize the use of multidetector CT in detection of pulmonary thromboembolism in children with sickle cell disease.     

Malignancy in perinatally human immunodeficiency virus-infected children in the United States

OBJECTIVES: To determine the incidence of and factors associated with malignancy in perinatally human immunodeficiency virus (HIV)-infected children in the United States. METHODS: Included were 2969 children followed in the Pediatric AIDS Clinical Trials Group (PACTG) 219/219C cohort from 1993 through 2003. Cancer incidence by sex, race, age, histology and highly active antiretroviral therapy (HAART) era (pre-HAART, 1993-1997; HAART, 1998-2003) was estimated, and the standardized incidence ratio contrasting infected and uninfected children was determined. Poisson regression was used to further investigate the relation between HAART use (> or =3 drugs of > or =2 classes, 1 of which was a protease inhibitor), CD4% and cancer. RESULTS: There were 37 cancers (17 prevalent and 20 incident) diagnosed in 2969 children for a prevalence of 0.6% [95% confidence interval (CI), 0.3, 0.9] and an incidence of 1.56/1000 person-years (95% CI 0.95, 2.41). Compared with uninfected children, the standardized incidence ratio was 10.08 (95% CI 5.87, 16.14). Incidence did not significantly differ by sex, race, age or HAART era. Of the cases, 35% were immunocompetent (CD4 > or =25%), 25% were moderately immunosuppressed (15%< or = CD4 < or =24%) and 40% were severely immunosuppressed (CD4 <15%) at diagnosis. In multivariate regression, the cancer rate was 3.09 (95% CI 1.22, 7.85) times higher in children with < or =2 years of HAART use than in children with >2 years of HAART and 3.20 (95% CI 1.32, 7.76) times higher in children with CD4 <15% at cohort enrollment than in children with CD4 > or =15%. CONCLUSION: Cancer incidence in this U.S. pediatric cohort was lower than that of European cohorts but was markedly higher than that of HIV-uninfected children. Cancer incidence was highest in children who were severely immunosuppressed and in children who received HAART for < or =2 years.     

Association of rib anomalies and malignancy in childhood

A relationship exists between tumours and malformations both generally and in particular combinations. This is also valid for minor errors of morphogenesis suggesting that embryonic tumours are an expression of aberrant intra-uterine morphogenesis. We speculated that these minor aberrations might also manifest in other morphological defects, especially in minor anomalies and malformations of the ribs. We reviewed chest roentgenographs of 1000 children with malignancies for rib anomalies and compared them to 200 patients with mainly infectious diseases. We found 242 rib anomalies in 218 children with tumours (21.8%) and 11 (5.5%) in children without malignancy. This difference was statistically highly significant (P<0.001). A high incidence of cervical ribs was found in neuroblastoma (33%), brain tumour (27.4%), leukaemia (26.8%), soft tissue sarcoma (24.5%), Wilms tumour (23.5%) and Ewing sarcoma (17.1%). Only neuroblastoma showed a high incidence of rib bifurcation (4.5%). The increased incidence of these mesenchymal defects in children with malignancies may be another clue for an altered morphogenesis in tumour origin. In neuroblastoma the rib anomaly may be another expression of neurocristopathy as proposed for the association of congenital heart disease and neuroblastoma.     

Back pain: A puzzle in children

Back pain in children is underdiagnosed and increases incidence in adolescence. A systematic approach can diagnose the most common causes: trauma, structural deformities, inflammatory diseases, infection and malignancy.     

Herpes zoster in otherwise healthy children

In normal infants and children, zoster can occur at any time after varicella or varicella vaccination. It is usually diagnosed clinically: a unilateral vesicular eruption following a dermatome or dermatomes. The incidence of zoster increases with age, although children who have had varicella during the first year of life (or in utero) are at increased risk of developing zoster. The incidence of zoster is less after varicella vaccination than after natural infection. Zoster in children is frequently mild, postzoster neuralgia rarely if ever occurs, and antiviral therapy is usually not needed. In a previously normal child with zoster, if the history and physical examination are normal, a laboratory search for occult immunodeficiency or malignancy is not needed. We present five cases of zoster in healthy children and review zoster in the pediatric age group.     

Management of Thrombotic Complications in Acute Lymphoblastic Leukemia

Acute lymphoblastic leukemia (ALL) is the most common type of cancer diagnosed in children, and has been reported as the most common malignancy associated with thromboembolism in the pediatric age group. Treatment with Escherichia coli asparaginase, concomitant steroids, presence of central venous lines, and thrombophilic abnormalities are established risk factors for thromboembolism. The incidence varies with age, co-morbidities and chemotherapy regimens but the risk is highest during the induction and intensification phases. Treatment is necessary in majority of children to prevent serious sequelae. Mortality from thromboembolic events in any location is 2 to 4 % and the risk of recurrence is 7 to 10 %, further enhanced in the setting of malignancy. Randomized trials of venous thromboembolism (VTE) management in pediatric patients with ALL are lacking due to the low overall incidence, resulting in considerable variation in practice. The objective of this article is to review current knowledge on the treatment and prevention of thrombosis associated with pediatric ALL.     

Nodular goiter and thyroid carcinoma in children and adolescents in a moderate endemic area (lower Silesia-Sudeten endemia) in the last twelve years

Although thyroid carcinoma is more common in the adult population, the risk of a nodule being malignant is greater in children. The aim of our present investigation was to ascertain the percentage of malignancy in nodular goiter observed in patients from the Lower Silesia region in the last 12 years. The examination included 60 children (12 boys and 48 girls) treated in our clinic from 1987 to June 1998. Age varied from 7 to 18 years (mean 14.8 +/- 2.4), most of them in the age group between 13 and 18 years. The following investigations were performed: TSH, T3, T4, thyroid ultrasonography, fine needle aspiration biopsy and Tc99 scintigraphy of the thyroid. Most of the patients were euthyroid; two children demonstrated pressure symptoms. All the patients were treated by operation. Histological examinations revealed the following: nodular goiter in 19 patients, cystic nodular goiter in 5, follicular adenoma in 20, fetal adenoma in 3, nodular goiter and follicular adenoma in 6, papillary carcinoma in 6, and follicular carcinoma in 1 patient. We concluded that an increased incidence of thyroid cancer has been noted in children with nodular goiter in Lower Silesia during the last 12 years. Thyroid cancer was observed mostly in patients with single nodules and was associated with a high risk of malignancy.     

Sinonasal adenocarcinoma: a rare second malignancy in long term retinoblastoma survivors

Retinoblastoma is the most common primary cancer of the eye in children. The incidence of second tumors in survivors of bilateral retinoblastoma and in survivors of unilateral retinoblastoma who presumably carry a germline RB1 mutation is documented. This article describes the previously unrecognized association of sinonasal adenocarcinoma as a second malignancy in retinoblastoma survivors. We present three cases who received radiation therapy as a part of their treatment and developed sinonasal adenocarcinoma as a second malignancy. Sinonasal adenocarcinoma should be considered as a second malignancy in retinoblastoma survivors who present with vague sinus symptoms.     

A retrospective review of undifferentiated malignancy in childhood

We reviewed the experience of children with "undifferentiated" cancer at The Children's Hospital of Pittsburgh (CHP) from 1971 through 1987. Of 2,095 patients 0-18 years old with diagnoses during that time of any cancer, the initial CHP pathology report rendered a diagnosis in 22 children (1.1%) of "undifferentiated malignancy" or "malignant tumor" (15 cases), "undifferentiated carcinoma" (two cases) or "anaplastic tumor or carcinoma" not otherwise specified (five cases). A review of pathologic findings using current methods and immunostaining led to the assignment of a specific diagnosis in 15 of the 20 cases so studied. Thus, the incidence of undifferentiated cancer by current criteria was reduced to no more than 0.23%. Two of the five tumors for which an alternative diagnosis could not be established were described as "rhabdoid," but because it is not clear that these tumors fit into a single category they were still considered to be undifferentiated. Clinical features and management of the 22 cases including the five persistently diagnosed as undifferentiated malignancy were heterogeneous. In the face of reassigned diagnoses, a number of patients would likely have received different chemotherapy as well as radiation. Nonetheless, seven patients with malignancy show no evidence of disease (NED), including several whose therapy, given the current best diagnosis, would not be considered to have been optimal. We recommend that for patients undergoing biopsy of a tumor, sufficient material be obtained for extensive pathologic evaluation. In this way, the diagnosis of undifferentiated malignancy in children can be almost eliminated.(ABSTRACT TRUNCATED AT 250 WORDS)     

Monitoring the therapy of acute lymphoid leukemia (ALL) in children--changes induced in clinical, cytological and immunological parameters during treatment of high malignancy ALL with ALL-BFM 88.

The ALL-BFM 88 RF greater than 1.7 treatment of high malignancy ALL patients in remission was monitored at the 4th week of Protocol I. The qualitative and quantitative processing of parameters indicating cellular transformations by light and electronmicroscopy was performed in lymphocytes separated from peripheral blood drawn at scheduled times of therapy. The immunophenotype of sample lymphocytes was determined by indirect immunofluorescent techniques, by listing the percentual level of CD2, CD3, CD4, CD8, CD19 surface antigens. The incidence of infections, confirmed clinically and bacteriologically, was recorded. The parameters of the patients were compared to those of healthy children. In the group of patients with high malignancy in the intensive period of ALL-BFM 88 RF greater than 1.7 therapy the incidence of cells rich in organelles, dense granules and vacuoles was significantly (p less than 0.05) higher compared to the control cells, poor in structures. During the weeks of induction and after the consolidating combination with VM-26+ARA-C the expression of surface antigens of the lymphocytes was reduced. That means that up to the introduction of maintenance treatment the presence of surface antigens remained below the range of normal deviation. These data obtained during monitoring revealed that the morphological and functional integrity of cells was damaged in patients with high malignancy ALL during intensive therapy, though only temporarily.     

Fractures in pediatric Ewing sarcoma

PURPOSE: To determine the incidence, timing, and clinical significance of long-bone fractures in children with Ewing sarcoma family of tumors (ESFT). PATIENTS AND METHODS: We retrospectively reviewed 93 consecutive cases of ESFT of the long bones seen at a single institution over the course of a 37-year period. RESULTS: Fracture occurred in 14 (15%) of 93 patients with long-bone ESFT, most commonly in the femur. Approximately 30% of patients with tumors of the femur had fractures at some point in the course of their disease. The incidence of fracture was highest among patients with tumors of the proximal third of the femur (50%); these fractures were usually present at the time of initial diagnosis. Nine (64%) of the 14 fractures occurred after the start of radiotherapy, and three of these were associated with either local recurrence or second malignancy. CONCLUSIONS: Patients with femoral ESFT are at high-risk for fracture. If fractures occur after the completion of therapy, recurrence or second malignancy should be suspected.     

Classification, incidence and survival analyses of children with CNS tumours diagnosed in Sweden 1984–2005

Aim:  Primary tumours in the central nervous system (CNS) are the second most common malignancy in childhood after leukaemia. Sweden has a high incidence and a high-survival rate in international comparative studies. This has raised the question about the type of tumours included in the Swedish Cancer registry. We therefore compared international data to the Swedish Childhood Cancer registry.
Methods:  Central nervous system tumours registered in the Swedish Childhood Cancer Registry were reclassified according to ICCC-3. Incidence and survival analyses were performed in the study population.
Results:  There were 1479 children (<15 years) in Sweden diagnosed with CNS tumours 1984–2005. The distribution of diagnoses was similar to that reported in other studies. The annual incidence was 4.2/100 000 children. The survival rates have not improved significantly between the two time periods before/after 1995 (70% vs. 74%; p = 0.10).
Conclusions:  The mean annual incidence of children with CNS tumours was 4.2/100 000 and has not increased during the study period. Survival rate for brain tumours at 10 years follow-up was 72%.     

Growth Hormone Treatment and Development of Malignancy: Recombinant Human Growth Hormone Does not Induce Leukemia in AKR/O-Mice

In 1988 several reports described leukemia in former/present growth hormone (GH)-treated children, and a doubled incidence of leukemia in GH-treated children was concluded in a workshop in Bethesda. A mouse strain (AKR/O) with a high incidence of leukemia was used as a model. AKR/O-mice in the preleukemic adult age and younger mice during rapid growth were treated with recombinant human GH (rhGH) in human therapeutic doses to see whether this treatment would affect the time and presentation of malignant disease. The malignant development did not appear earlier or in a different way in the animals receiving rhGH from day 6 to 50 than in their appropriate controls. A borderline protective effect to the development of leukemia was seen in the adult group receiving rhGH; in this group antibodies to hGH also developed. We conclude that in this experimental model human therapeutic doses of rhGH do not influence the development of malignancy in the AKR/O mice.     

SEER update of incidence and trends in pediatric malignancies: acute lymphoblastic leukemia

BACKGROUND: Acute lymphoblastic leukemia (ALL) represents the most common malignancy of childhood. Its incidence peaks in children just before school entry age; i.e., in 2-3 year olds. It is known to be more common in white children in the USA; the incidence is also higher in boys than girls. PROCEDURE: We reviewed the 5,379 cases of ALL among persons under 20 years of age in the National Cancer Institute's Surveillance Epidemiology and End Results (SEER) database. RESULTS: The overall incidence of ALL was 26/10(6) person-years between 1973 and 1998, but increased from 19/10(6) person-years in 1973-77 to 28/10(6) person-years in 1993-98 (P < 0.0001). Rates were 44% higher among Whites compared to Blacks (27/10(6) person-years vs. 15/10(6) person-years, P < 0.0001). In 1992-1998, the incidence rate for Hispanics was 43/10(6) person-years, significantly higher than non-Hispanics (28/10(6), P < 0.0001). White children with ALL had better 5-year survival rates than Black children with ALL (71% vs. 58%, P < 0.0001), and 5-year survival was poorest among black males. CONCLUSIONS: ALL incidence has increased over the examined 25-year period. The rate in US whites is higher than that of US Blacks, and the rates in the Hispanic subgroup are the highest of all. While the median survival period is now more than 10 years overall, the 5-year survival rate remains poor for Black males under 4 years of age. Socioeconomic factors do not account for this difference, which may relate to ALL subtype distribution.     

Venous thromboembolism in pediatric patients: epidemiologic data from a pediatric tertiary care center in Alabama

Venous thrombosis is an infrequent but serious cause of hospitalization in children. The epidemiology and natural history remains incompletely defined, especially in geographically distinct regions of the United States. We thus evaluated thrombosis in a single children's hospital over a 3-year period. Of 41,906 hospitalizations, 92 children were identified for review. The incidence of thrombosis was 21.9 per 10,000 admissions (0.22%). Venous thrombosis was of equal incidence in African-American and white patients. Locations of thrombosis included deep venous (51%), pulmonary (21%), renal vein (8%), intrahepatic (8%), and intracranial (12%). Risk factors for thrombosis included central catheter (32%), malignancy (18%), systemic infection (21%), neurologic disability (9%), cardiac (4%), nephrotic syndrome (3%), and autoimmune (6%). Six of 92 patients (7%) had thrombophilia. Positive family history of venous thromboembolism (VTE) or thrombophilic disorder predicted an abnormal test. Treatment included low-molecular-weight heparin (n=53), coumadin (n=12), heparin (n=10), tissue plasminogen activator (n=6), argatroban (n=1), thrombectomy (n=2), inferior vena cava filter (n=2), and no treatment (n=23). Seventy-seven percent demonstrated resolution of the VTE, 14% had persistent or recurrent VTE, and 9% died. Causes of death were malignancy, prematurity, septicemia, and congenital heart disease. Venous thrombosis is a serious comorbidity in hospitalized children. In our population, African-Americans had an equal incidence of VTE as whites. Positive family history predicted thrombophilia.     

Tuberculosis in oncology patients

BACKGROUND: There is a dearth of studies addressing the incidence and clinical presentation of tuberculosis (TB) in children with cancer. AIM: To evaluate the incidence of TB in paediatric oncology patients at Tygerberg Hospital, located in a Cape Town area of high TB prevalence, and to describe the clinical characteristics of the disease in this particular group of patients whose treatment typically suppresses their immune response. METHODS: We reviewed the records of 625 paediatric oncology patients admitted from 1 January 1991 to 31 December 2005. Of these, 87 received treatment for TB; however, only 57 cases had sufficient data to support a diagnosis of TB and only these were used for further analysis. RESULTS: In the children with TB, acute lymphoblastic leukaemia (ALL) was the most common malignancy (13/57, 22.8%). The incidence of TB in the study group was 9117/100,000/year, which is 22 times higher than the overall TB incidence reported in children from a similar background. Importantly, 47% of the active infections appeared in the 1st 5 months of chemotherapy, suggesting reactivation of latent TB. CONCLUSIONS: Identifying latent TB in our patients and providing prophylactic treatment during the initial months of chemotherapy might have prevented disease progression in these cases. Routine screening of paediatric oncology patients for latent TB infection and exclusion of active disease prior to initiation of cancer therapy might be indicated in TB-endemic areas.