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.

The effect of vitamin A status in children treated for cancer.

Chemotherapy for cancer can cause immunocompromise. The authors speculated that children with cancer and low vitamin A plasma levels were more susceptible to cancer treatment-related complications than children who are not vitamin A deficient. A cohort of 49 children with cancer were followed from diagnosis until death or for at least 5 years. Plasma retinol levels were determined at diagnosis. Complications of treatment were recorded. Children with low retinol levels at diagnosis tended to have more chance to develop febrile neutropenia (p = .052). Children with fever had lower mean vitamin A levels at diagnosis than those who did not suffer febrile episodes. In a childhood population with a high prevalence of vitamin A deficiency, routine vitamin A assessment and supplementation in children with cancer appears indicated.

Malignant liver tumors in South African children: a national audit.

BACKGROUND: Malignant liver tumors (mostly hepatoblastoma [HB] and hepatocellular carcinoma [HCC]) are uncommon, representing 0.5%-2% of childhood malignancies worldwide. The pattern of liver tumors appears to differ in Southern Africa as a result of infectious factors (e.g., hepatitis B/retroviral disease (HIV). This study aimed to assess recent changes in the prevalence and surgical management of liver tumors in South African children. METHODS: Data were obtained from the tumor registry and pediatric oncology units in South African hospitals to audit and review the epidemiology, treatment, and outcome of malignant hepatic tumors in South African children. RESULTS: Malignant primary hepatic tumors were reported in 274 children (ages 0-14 years) from 1988 through June 2006. Of these 134 (48%) had HB; 77 (27%) had HCC (9 [3%] fibrolamellar subtype); 38 (13%), vascular tumors; and 17 (6%), liver sarcomas. In a further 8 patients (3%) other tumors included lymphoma and endodermal sinus tumor. Vascular tumors included hemangioendotheliomas (12), and there were 5 malignant tumors in children with HIV, including 1 angiosarcoma and 13 Kaposi sarcoma-like tumors. Hepatoblastoma occurred at a mean age of 1.47 years, and none were encountered in patients > 4 years of age. Hepatocellular carcinoma mostly occurred in the older patients (mean age: 10.48 years), but 6% presented in patients < 8 years of age (10 months, 2, 2.6, 5, 5, and 6 years). Hepatic sarcoma occurred at a mean age of 7.66 years and had a female predominance (M:F ratio: 0.4). The relative HCC prevalence (male predominant: hepatitis B related) was reflected in the low HB:HCC (1.67) ratio. However, a significant decrease in HCC was attributed to the effect of hepatitis B inoculation. There appeared to be an increase in the incidence of vascular tumors, presumably the result of an increase in Kaposi-like sarcoma in retrovirus-positive patients. The surgical resection rate was low because most patients presented late, with advanced disease. Survival was 11% and 52% for HB and HCC, respectively, and was related to chemotherapeutic response and complete surgical resection. CONCLUSIONS: Liver tumors appear to have a different epidemiological pattern in South Africa. The observed increased HCC prevalence appears to be decreasing with hepatitis B vaccination. Retroviral disease does not yet appear to have a major influence on the distribution of liver tumors in South Africa, although it possibly affects the vascular tumor prevalence.

Hemopure transfusion in a child with severe anemia.

A 23-month-old girl presented with heart failure from extremely severe sickle cell anemia. The family refused blood transfusion on religious grounds (Jehovah's Witness). Alternative options acceptable to this religion, such as iron, erythropoietin, or folic acid were rejected as useless in the particular situation of the child. The patient was transfused with Hemopure, a product that consists of polymerized bovine hemoglobin. This is the first case reported in the literature of a child transfused, in an emergency situation, with this product.

Improved outcome in South African children of mixed ethnicity treated for all.

A historical cohort study with an analytical component was conducted to determine whether risk-appropriate chemotherapy can improve survival in children of mixed ethnicity with ALL. Eighty-one coloured children treated for ALL in South Africa were divided into 2 groups: group A (n = 39), treated prior to 1992, and group B (n = 42), treated after 1992. A comparison was made of survival, treatment complications, and supportive measures. The two groups were comparable. The mean nadirs of the white cell count (p < .01), platelet count (p = .01), and hemoglobin value (p < .01) were significantly lower in group B. The survival rate of 37% in group A improved to 66% in group B (p = .025). The results show that a risk-adapted regimen increased survival in children of mixed ethnicity in the Western Cape, despite increased hematological toxicity and episodes of febrile neutropenia.

Incidence of acute lymphoblastic leukaemia in white and coloured children in the Western Cape.

UNLABELLED: Objectives. To record the age-specific incidence rate (ASIR) for diagnosed acute lymphoblastic leukaemia (ALL) in coloured and white children aged 0 - 12 years in the Western Cape (WC). DESIGN: A retrospective population-based study using the 1991 population census to calculate the mean annual childhood population and the ASIR for ALL in the 0 - 4, 5 - 9 and 10 - 12-year age groups in rural and Cape Town metropolitan areas for the period 1983 - 1999. Odds ratios were calculated using EpiInfo 2000. SETTING: Registry records of the paediatric cancer units at Tygerberg and Red Cross War Memorial Children's hospitals where all children with ALL in the WC were initially treated. SUBJECTS: All white and coloured children aged 0 - 12 years diagnosed as having ALL from 1983 - 1999. OUTCOME MEASURES: The ASIR by age and ethnic group in rural and metropolitan patients in the WC. RESULTS: The estimated annual childhood population in 1991 was 709 151 with 80.4% coloured and 19.6% white children, of whom 60% were resident in the Cape Town metropolitan area and 40% in the rural area of the WC. Of 246 children with ALL diagnosed in the period 1983 - 1999, 144 were male and 102 female. The ASIR in coloured children aged 0 - 4 years was 17.1/10(6) in the rural and 30.5/10(6) in the metropolitan area, compared with 55.7/10(6) and 56.2/10(6) respectively in white children. In the 5 - 9-year age group the ASIR in coloured children was 10.0/10(6) in the rural and 16.6/10(6) in the metropolitan area compared with 27.6/10(6) and 26.7/10(6) respectively in white children. The 10 - 12-year age group had comparable incidence rates in both populations and geographical areas. Only one case occurred within a 20 km radius of the Koeberg nuclear reactor. CONCLUSIONS: White children have an ASIR for ALL comparable to rates of diagnosis in the USA, while only half as many coloured children aged 0 - 9 years were diagnosed in both the rural and metropolitan areas. This contrast may indicate significant underdiagnosis of ALL in coloured children over the period in question. The change in health policy since 1994, which has improved access to primary health care, may improve the rate of diagnosis among coloured and black children.

Haemophilia patients aged 0-18 years in the Western Cape.

OBJECTIVES: To record the number of haemophilicas aged 0-18 years in the Western Cape (WC), what event led to the diagnosis, the level of clotting factor, treatment, functional status of their joints and impact of the disease on the family. DESIGN: A prospective study of patients registered with the South African National Haemophilia Registry and new patients, utilising the patients' paediatricians, hospital records, patient and guardian interviews, physical examination and provincial nurse haemophilia co-ordinators. SETTING: Haemophilia care centres at the three WC academic hospitals, regional hospitals and homes of patients. Two elective medical students, MHH and JJH, collected the information. SUBJECTS: All boys with confirmed haemophilia A or B in the WC. OUTCOME MEASURES: Events that led to diagnosis, degree of haemophilia, use of clotting factor, functional status, and effect on family. RESULTS: Of 78 patients (59 haemophilia A, 19 haemophilia B) identified, 49 could be studied. Forty-three per cent had severe, 29% moderate and 22% mild disease (6% unknown). Family history was present in 49%, but led to diagnosis in only 12%. The most common first symptoms were subcutaneous and mucosal bleeding. Delay in diagnosis varied from 0 to 9 months. Twenty-nine per cent of guardians were suspected of child abuse. RSA produced clotting factor was used 'on demand' in 73% of patients, for periodic prophylaxis in 20% and as continuous prophylaxis in 7%. Joints were functionally restricted in 43% of patients. The majority of guardians (59%) said the disease had a major impact on the family. CONCLUSIONS: The diagnosis of haemophilia in children with a positive family history was often delayed. Haemophilia causes significant morbidity in our patients and their families.

[Robotic and navigation systems: surgical practicability and benefit for the patient?]. / Roboter- und Navigationssysteme: Praktikabilität für den Operateur--Nutzen für den Patienten?

The use of robotics and navigated systems to prepare, perform and reinforce surgical interventions is described by the term "computer aided surgery" (CAS). CAS is expected to make surgery even more precise, safer and cheaper. It comprehends computer based supporting systems (e. g. therapy planning, simulation, navigation), assisting systems, programmable automates and the so called master-slave-systems. When introducing technical innovations, the potential benefit of the patient is the essential issue. Then only practicability under clinical conditions, and additional aspects can be discussed. Conclusively, less spectacular applications of CAS like computer based supporting or assisting systems are more relevant for current practical use than visionary robotic systems.

Long term survival of children with Burkitt lymphoma in Malawi after cyclophosphamide monotherapy.

BACKGROUND: Between 1991 and 1997, limited funding at times restricted available treatment for children with Burkitt lymphoma (BL) to cyclophosphamide (CPM) monotherapy at Lilongwe Central Hospital, Malawi. Our objective was to assess long-term survival in Malawian children with Burkitt lymphoma (BL) who had received one or more treatments with intravenous CPM at 40 mg/kg/dose at 14-day intervals. PROCEDURE AND RESULTS: The study population consisted of 92 children in whom BL had been confirmed on fine needle aspirates (FNA), a home address had been documented on discharge from hospital, and the treatment records could be verified. Only the clinical site(s) of disease had been recorded. The M:F ratio was 1.4 and median age 8 years. A clinical officer on motorcycle attempted to locate the given addresses and interview parents or other sources. In 19 patients, the address was incorrect. Of 73 evaluable patients, 40 children are alive at a mean follow-up time of 59 (range: 29-104) months. The survival rate was 63.5% in 52 children with BL of the head only, and 33.3% in 21 children with primary disease involving the abdomen or other sites. Survivors had received a median number of 6 (range: 1-12), non-survivors 4 (range: 1-12), and untracable children 3 (range: 1-11) courses of CPM. CONCLUSIONS: We confirmed that CPM could cure children with facial and abdominal BL. The unavoidable bias in the selection of patients and the variable amount of CPM given, precludes accurate survival estimates. A prospective study with proper staging, assessment of FNA, marrow and cerebrospinal fluid with modern techniques, a standard treatment protocol, and adequate follow-up will better define the current therapeutic value of CPM monotherapy. CPM can be purchased at about 3 US dollars per 500 mg.

Band 3 Cape Town (E90K) causes severe hereditary spherocytosis in combination with band 3 Prague III.

Hereditary spherocytosis (HS) is an inherited haemolytic anaemia, characterized by spheroidal, osmotically fragile red blood cells. This disorder exhibits heterogeneity in terms of both clinical severity and underlying molecular defect. We have studied a South African Cape Coloured individual with severe HS owing to a band 3 deficiency caused by two mutations, occurring in trans, in the band 3 gene: a novel variant that we have designated band 3 Cape Town and a previously described mutation, band 3 Prague III. Analysis of erythrocyte membrane proteins indicated a deficiency of both band 3 and protein 4.2, as well as a decreased functional capacity of band 3 to transport anions. Band 3 Cape Town is defined by a GAG-->AAG point mutation at codon 90, substituting a glutamic acid with a lysine in the cytoplasmic domain of the molecule, while band 3 Prague III is a codon 870 CGG-->TGG point mutation, replacing an arginine with a tryptophan in the transmembrane region of band 3. mRNA is transcribed from both mutant alleles, implying that mutant proteins are synthesized, but are either degraded prior to membrane incorporation or insertion is impaired. We conclude that the combination of these two mutations exacerbated the clinical presentation of the proband.

Prognostic value of day 14 blast percentage and the absolute blast index in bone marrow of children with acute lymphoblastic leukemia.

The product of the percentage blasts on the bone marrow aspirate (BMA) and the biopsy cellularity has been termed the "absolute blast index aspirate" (ABI-aspirate) and is used to measure disease response on day 7 of induction therapy. The authors compared the event-free survival (EFS) in high-risk and standard-risk patients as identified by the ABI-aspirate and the BMA percentage blasts on day 14 of induction therapy. Both indices identified high-risk cases. EFS of patients categorized as high-risk by these 2 methods and the high-risk criteria used by the authors' service (WCC of > 20 x 10(9)/L, age < 2 and > 8 years and a peripheral blood blast count of > 1.0 x 10(9)/L on day 8 of induction) did not differ. There was concordance between patients identified as high risk by all 3 methods. The results confirmed the prognostic value of the ABI-aspirate and the BMA percentage blasts on day 14 of induction therapy, but these methods were not superior to the high-risk criteria currently in use.

Three-dimensional navigated laparoscopic ultrasonography: first experiences with a new minimally invasive diagnostic device.

BACKGROUND: A three-dimensional (3D) display of diagnostic imaging methods is technically feasible and increasingly important. However, the technical integration of laparoscopic ultrasound and 3D image reconstruction has not yet been realized. For this purpose, an electromagnetic navigation system was integrated into the tip of a conventional laparoscopic ultrasound probe. This first experience with a certified prototype of a navigated 3D laparoscopic ultrasound probe is reported. METHODS: Navigated 3D laparoscopic ultrasound was compared with the imaging data of 3D-navigated transcutaneous ultrasound and 3D computed tomography (CT) scan. The 3D CT scan served as the "gold standard." Clinical applicability, imaging quality, diagnostic potential, and accuracy in volumetric assessment of various well-defined hepatic lesions were analyzed. RESULTS: Navigated 3D laparoscopic ultrasound facilitates exact definition of tumor location and margins. As compared with the "gold standard" of the 3D CT scan, 3D laparoscopic ultrasound has a mild tendency to underestimate the volume of the region of interest (ROI) (D 3.1%). A comparison of 3D laparoscopy and transcutaneous 3D ultrasonography clearly demonstrated that the former is more accurate for volumetric assessment of the ROI. CONCLUSIONS: Three-dimensional laparoscopic ultrasound imaging with a navigated probe is technically feasible. The technique facilitates detailed ultrasound evaluation of laparoscopic procedures involving visual, in-depth, and volumetric perception of complex liver pathologies. Navigated 3D laparoscopic ultrasound may have the potential to improve the significance of laparoscopic ultrasonography, and additionally to become a valuable technology for planning and improving interventions guided by laparoscopic ultrasound.

Viral isolates during febrile neutropaenia in children with cancer.

We prospectively studied South African children with cancer for viral isolates during episodes of febrile neutropaenia. Viruses were found in seven (31.8 per cent) and bacteria in five (22.7 per cent) of 22 episodes. The most common isolate was the herpes simplex virus and the most common source was from nasopharyngeal aspirates. There was no dual detection of viral and bacterial isolates. This study emphasizes the important contribution of viruses to febrile neutropaenia.

Haematological abnormalities in children with tuberculosis.

Over a 16 month period 307 children with suspected tuberculosis (TB) and an available full blood count (FBC) seen at Tygerberg Hospital in South Africa were evaluated and categorized as confirmed (A), probable (B), and no TB (C) according to WHO criteria. There was no difference in the mean age of the 168 group A (33.6 months), 83 group B (34.4 months), and the 56 group C (31.6 months) children. A lower mean haemoglobin (Hb 10.2 vs. 10.8 g/dl) was the only significantly different haematological parameter in children with TB compared with the comparison group (Group C). There were no differences in median total white cell count, neutrophils, lymphocytes, monocytes, platelets, or the proportion of children in each group with anaemia, microcytosis, neutrophilia, neutropenia, lymphocytosis, lymphopenia, monocytosis, thrombocytosis or thrombocytopenia. The most common haematological abnormalities in children with TB were the presence of anaemia, neutrophilia, and monocytosis but these changes were found with equal frequency in control patients. Although haematological abnormalities are fairly common in children with TB, in a developing country these abnormalities also occur frequently in children with other non-tuberculosis respiratory infections. An FBC has no diagnostic predictive value when investigating a child for TB.

Nutrition, morbidity, and survival in South African children with Wilms' tumor.

Fifty-nine children with Wilms' tumor (WT) were divided into a normal or poorly nourished group according to anthropometric parameters. The 2 groups were compared for morbidity and survival. There was no difference in the median age or stage of disease in the 38 well nourished and 21 poorly nourished children. There was no difference in the number of children in the normal or poorly nourished group who developed a raised urea or creatinine level, febrile episodes, severe stomatitis, varicella, or upper or lower respiratory infections, or who needed intravenous antibiotics, parenteral nutrition, or red cell and platelet transfusions. Projected survival rate was 56 and 74% for normal and poorly nourished children, respectively (p = .3). Poor nutrition at diagnosis, as determined by anthropometry, had no effect on the morbidity of treatment or survival in children with WT. Based on these results, selective dietary supplementation instead of routine intensive parenteral nutritional support for all children with WT is recommended in countries with limited resources.