The changing role of radiotherapy in AIDS-related malignancies.

OBJECTIVE: To review the current literature on the role of radiotherapy in AIDS-related malignancies published since 1997. METHODS: A comprehensive literature review was undertaken to review the recent advances in the role of radiotherapy in the management of AIDS-related malignancies. This was combined with the clinical experience from our two London treatment centres for AIDS-related malignancies. A Medline/Pubmed search was performed for articles published since 1997, the year of the previous review, which also coincides with the widespread usage of highly active antiretroviral treatment (HAART). The MESH search terms used were 'HIV or AIDS' and 'radiotherapy'. This search yielded a total of 86 references. CONCLUSIONS: HAART has had a major impact on the role of radiotherapy in AIDS-related malignancy. The use of HAART has led to a decline in the incidence of Kaposi's sarcoma (KS) and non-Hodgkin's lymphoma and has been associated with an improved prognosis in systemic non-Hodgkin's lymphoma in people with HIV. In addition HAART alone has been successfully used as therapy for early KS lesions. Chemoradiotherapy remains the mainstay of management for anal cancer, has a central role in cervical cancer and non-AIDS defining malignancies in this population.

Primary cardiac lipoblastoma.

Lipoblastoma is a benign adipose tumor in children that has been described in various anatomic locations, most commonly the extremities. We describe the case of a 17-month-old boy diagnosed with cardiac lipoblastoma, a previously unreported primary cardiac tumor in children. Our patient presented with symptoms of coughing, wheezing, and hoarseness and was found to have a large mediastinal mass, which narrowed the left mainstem bronchus and compressed the right atrium and superior vena cava, causing superior vena cava syndrome. Surgical exploration revealed an intrapericardial soft tissue mass arising from the area of the posterior interatrial septum. Grossly, the resected mass was lobulated, pale yellow, and fatty with focal areas of gray myxoid tissue. Microscopically, the tumor consisted of both immature and mature adipocytes, with focal vascular myxoid areas containing lipoblasts, diagnostic of lipoblastoma. Two months after surgery, the patient was in good health without evidence of recurrence.

Pattern of local recurrence after conservative surgery and radiotherapy for soft tissue sarcoma.

PURPOSE: Over the past three decades our centre has adopted a policy of conservative surgery followed by adjuvant radicaldose radiotherapy for medium-and high-grade soft tissue sarcomas. For all cases of local recurrence following this treatment we aimed to define the spatial relationship between sites of recurrence and the positions of the phase 1 and 2 radiotherapy volumes. PATIENTS: We identified 25 cases of local recurrence recorded on our soft tissue sarcoma database between 1986 and 1999 inclusive. We excluded patients with macroscopic residual disease following surgery. Most patients were treated with a phase I volume corresponding to the entire muscle compartment (50 Gy in 25 fractions over 5 weeks) and a phase II volume corresponding to the tumour bed (10 Gy in five fractions). Six of the patients were treated according to a hyperfractionated regimen. METHODS: For each case we reviewed the diagnostic imaging, planning radiographs and prescription sheets. We audited whether treatment had been given according to protocol and defined whether recurrence had arisen in the phase 1 volume, phase 2 volume or 'out of field'. RESULTS: Four (16%) patients recurred within the phase I volume, 17 (68%) recurred within the phase II volume and four (16%) outside the irradiated volume including one marginal recurrence. In six patients there had been deviation from our radiotherapy protocol (usually unavoidable) including all three true out of field recurrences. DISCUSSION: The majority of recurrences occur in the phase 2 volume. Prospective multi-centre data collection and, ideally, a prospective randomised trial are required to formulate an improved treatment policy with respect to radiotherapy margins and dose.

Mutations in the cardiac transcription factor NKX2.5 affect diverse cardiac developmental pathways.

Heterozygous mutations in NKX2.5, a homeobox transcription factor, were reported to cause secundum atrial septal defects and result in atrioventricular (AV) conduction block during postnatal life. To further characterize the role of NKX2.5 in cardiac morphogenesis, we sought additional mutations in groups of probands with cardiac anomalies and first-degree AV block, idiopathic AV block, or tetralogy of Fallot. We identified 7 novel mutations by sequence analysis of the NKX2.5-coding region in 26 individuals. Associated phenotypes included AV block, which was the primary manifestation of cardiac disease in nearly a quarter of affected individuals, as well as atrial septal defect and ventricular septal defect. Ventricular septal defect was associated with tetralogy of Fallot or double-outlet right ventricle in 3 individuals. Ebstein's anomaly and other tricuspid valve abnormalities were also present. Mutations in human NKX2.5 cause a variety of cardiac anomalies and may account for a clinically significant portion of tetralogy of Fallot and idiopathic AV block. The coinheritance of NKX2.5 mutations with various congenital heart defects suggests that this transcription factor contributes to diverse cardiac developmental pathways.

Lobar emphysema due to anomalous aortic origin of the left pulmonary artery.

The unusual case of an infant with aortic origin of the left pulmonary artery is presented. The patient developed a rare complication of lobar emphysema due to bronchial compression from the enlarged right pulmonary artery. Operative anastomosis of the left pulmonary artery to the pulmonary trunk was successful, with subsequent resolution of the lobar emphysema.

Pilot study of nimorazole as a hypoxic-cell sensitizer with the "chart" regimen in head and neck cancer.

PURPOSE: A potential disadvantage of accelerated fractionation in radiotherapy is the lack of time for reoxygenation, so that hypoxia becomes a more potent cause of failure. Accordingly, we have combined nimorazole, the only hypoxic radiosensitizer shown to significantly improve local control in head and neck cancer, with continuous hyperfractionated accelerated radiation therapy (CHART). METHODS AND MATERIALS: Twenty-two patients with locally advanced (stage IV) squamous cell carcinoma of the head and neck were treated with escalating doses of nimorazole given concomitantly with CHART (three fractions of 1.5 Gy per day, spaced 5 1/2 hours apart, on 12 consecutive days). All patients received 1.2 g/m2 nimorazole 90 minutes before each first daily fraction. Seventeen patients received a further 0.6 g/m2 before each second daily fraction and six of these patients received an additional dose of 0.6 g/m2 before each third fraction. RESULTS: The three times daily schedule yielded mean plasma drug concentrations at the time of irradiation of 37.7 microg/ml with the morning fractions, 31.2 microg/ml with the afternoon fractions, and 30.4 microg/ml with the evening fractions. In view of these results the midday dose was increased to 0.9 microg/m2 in an ongoing Phase II study. Drug toxicity was limited to nausea and vomiting apart from two cases of mild paraesthesia at the highest dose level. CONCLUSIONS: Comparison with a historical group of patients, treated with the CHART regimen alone and matched for irradiation volume and technique, showed that nimorazole did not increase the severity of acute normal tissue radiation effects. Encouraging tumor responses have been seen in the patients receiving nimorazole with every radiotherapy fraction.

Lymphocyte subsets in cord blood of preterm infants: effect of antenatal steroids.

The objective of this study was to evaluate prospectively the influence of gestational age (GA) and short-term antenatal steroids on total lymphocyte count and lymphocyte subsets in cord blood from preterm infants. Two-color flow cytometric analyses of lymphocyte subsets were performed on cord blood collected from 67 infants. These infants were grouped according to GA: group I (term, n = 19); group II (GA 33-37 weeks, n = 25); group III (GA <33 weeks, n = 23). The mean absolute lymphocyte counts (ALC) in groups I, II and III were 5.6 +/- 2.5 x 10(3)/ microl, 4.3 +/- 1.5 x 10(3)/ microl and 3. 5 +/- 1.8 x 10(3)/ microl respectively. The mean values for CD4+ lymphocytes in groups I, II and III were 2.7 +/- 0.8 x 10(3)/ microl, 2.0 +/- 0.8 x 10(3)/ microl and 1.6 +/- 0.9 x 10(3)/ microl respectively. Mean values for CD8+ lymphocytes were 0.9 +/- 0.3 x 10(3)/ microl, 0.6 +/- 0.3 x 10(3)/ microl and 0.5 +/- 0.3 x 10(3)/ microl respectively. With decreasing GA, there was a statistically significant decrease in ALC (p = 0.0035), CD4+ lymphocytes (p = 0. 0013) and CD8+ lymphocytes (p = 0.0064). We then evaluated the effect of antenatal steroids, now routinely administered to women with preterm onset of labor to facilitate fetal lung maturation, and found that after adjusting for GA, infants of women on antenatal steroids had significantly fewer ALC (p = 0.0001), CD4+ lymphocytes (p = 0.02) and CD25+ lymphocytes (p = 0.03). In this population of infants, the decreased number of lymphocytes seen at younger GAs is associated with antenatal steroid use.

Sternal defects associated with congenital pericardial and cardiac defects.

We describe three cases of sternal defects of varying severity associated with other congenital anomalies. In the most severe case, both anterior and posterior defects were seen, with near-absence of the sternum and pericardium continuous with a large omphalocele. This resulted in external location of organs usually confined within the thoracic and abdominal cavities. A ventricular septal defect was present, and the arterial duct was absent. The course of the ascending aorta was anomalous. The baby had anencephaly and rachischisis. In the intermediate case, a proximal sternal cleft was associated with shortening of the sternum, and absence of the manubrium. Anterior pericardial and diaphragmatic defects were seen, while a scalp defect and an encephalocele were present on the posterior aspect of the head. This baby had tricuspid atresia. The remaining case had only an anterior defect with a shortened sternum. A supra-umbilical omphalocele contained a left ventricular diverticulum without interposing pericardium or diaphragm. Ventricular and atrial septal defects were present. The first two cases can be considered as representing failure of development of both an anterior and a posterior midline field. The third case, much milder than the other two, represents failure of development of an anterior field.

Carbon dioxide (CO2) angiography in children.

BACKGROUND: When iodinated contrast material is contraindicated, carbon dioxide (CO2) gas can be injected intravascularly to produce high-quality digital subtraction angiograms. OBJECTIVE: CO2 angiography, although previously described in adults, has never before been reported in children. MATERIALS AND METHODS: We present three children with renal transplants who required renal angiography. Because of elevated creatinine levels, iodinated contrast was not used to search for possible renal artery stenosis. Instead, CO2 angiography was used to evaluate the renal artery anastomosis. RESULTS: In all three cases, the renal artery anastomosis was clearly visualized using CO2 angiography and showed no evidence of renal artery stenosis. CONCLUSION: Digital CO2 angiography is an effective method for pediatric renal angiography. The technique can easily be adapted for virtually any angiographic laboratory capable of digital subtraction imaging. Digital CO2 angiography also lacks the risks of a conventional iodinated contrast medium, namely nephrotoxicity, allergic reaction and volume overload.

Tetralogy of Fallot with absent pulmonary valve and bronchial compression: treatment with endobronchial stents.

Absent pulmonary valve syndrome (APVS) is a rare congenital cardiac lesion. The lesion includes ventricular septal defect, overriding aorta, and absence of the pulmonary valve, with resultant pulmonary incompetence. It has been suggested that the pulmonary incompetence induces intrauterine dilatation of the pulmonary artery, which leads to tracheobronchial compression. One of the presenting features in infants with APVS is severe airway obstruction, which may be difficult to manage. We report an infant who benefited from bilateral endobronchial endoscopic stent placement.

Cutaneous T-cell lymphoma, tropical spastic paraparesis, cerebral vasculitis, and protein S deficiency in a patient with HTLV-I.

The clinical spectrum of retroviruses is expanding rapidly. Human T-cell lymphotropic virus type I (HTLV-I) was the first retrovirus to be described, and its role had been established in adult T-cell leukemia/lymphoma and tropical spastic paraparesis. We report the case of a 35-year-old woman with HTLV-I and the unusual combination of cutaneous T-cell lymphoma, tropical spastic paraparesis, cerebral vasculitis, and protein S deficiency. We discuss the relationship of all her diseases to HTLV-I.

Cytolytic response to HIV in patients with HIV disease treated with extracorporeal photochemotherapy: preliminary study.

Extracorporeal photochemotherapy (photopheresis), an immunomodulatory therapy that targets circulating T helper lymphocytes, has been applied to the management of human immunodeficiency virus (HIV) disease. Any therapy that exerts its actions on CD4+ T cells has the potential of exacerbating HIV infection. Therefore, it was necessary to observe immune function during treatment. Because cytotoxic T lymphocytes (CTL) and natural-killer cells are thought to play an important role in the response against HIV infection, we examined the effect of photopheresis on HIV cytolytic activity. The study group consisted of seven patients with late-stage HIV disease who had not received any previous treatment for HIV infection. Patients were treated exclusively with photopheresis on two consecutive days each month for 14-32 months (average, 25 months). Peripheral lymphocytes, collected at various points during treatment, were used as effectors in a 51Cr release assay. Epstein-Barr virus (EBV)-transformed autologous B cell lines transfected with recombinant vaccinia vectors that expressed the HIV env (gp120, gp41) and gag (p24) proteins were used as target cells. All seven patients demonstrated relatively constant levels of cytolysis (>10% above controls) during treatment in the context of stable CD4+ T cell counts and a stable clinical status. These results suggest that extracorporeal photochemotherapy did not impair the cytolytic response to HIV infection and may have enhanced it in some patients.

Extracorporeal photochemotherapy in a patient with Ki-1-positive anaplastic large-cell lymphoma.

A 57-year-old man with Ki-1 anaplastic large-cell lymphoma treated with extracorporeal photochemotherapy is described.

Silicone granuloma in acral skin in a patient with silicone-gel breast implants and systemic sclerosis.

A 68-year-old white woman was referred to us by her rheumatologist for possible participation in a clinical study of photopheresis for scleroderma. In February 1993, she noticed edema of her distal phalanges, Raynaud's phenomenon in both hands, flu-like symptoms, fatigue, intermittent diarrhea, abdominal pain, tearing in both eyes, dyspnea on exertion, dysphagia, and odynophagia. Bilateral silicone-gel breast implants had been placed 12 years before; 2 months before her present evaluation, they were removed and found to be ruptured. Physical examination revealed edema, limited to the fingers and hands bilaterally, and slight induration of the skin on the dorsum of both hands and distal forearms. The remainder of the physical examination was normal. According to our study protocol, a skin biopsy specimen from the dorsum of the right hand was taken, but all other laboratory investigations were refused. Histopathologic examination revealed multiple clear spaces of varying sizes in the dermis and multinucleated macrophages containing small refractile particles, characteristic of silicone granuloma (Figs. 1 and 2); however, the specimen showed no evidence of scleroderma. X-ray energy dispersive analysis by scanning electron-microscopy confirmed the presence of elemental silicon in the small refractile particles. The patient did not receive any treatment after her diagnosis and shortly thereafter, she was lost to follow-up.

Right ventricular outflow muscle in tetralogy of Fallot: Histologic and immunohistochemical monoclonal antibody analysis.

To evaluate progressive muscular right ventricular outflow tract (RVOT) obstruction in tetralogy of Fallot (TOF), we hypothesized that this tissue would demonstrate more prominent selected immunohistochemical markers of myogenous cell differentiation, growth factor/receptor, and extracellular matrix. Sections of formalin-fixed, paraffin-embedded myectomy tissue obtained from RVOT at the time of surgical correction of TOF (n = 32; ages = 3 months through 13 years) were compared with age-matched tissue from the RVOT of normal control hearts (n = 12) obtained at autopsy after non-cardiac death. Examining by light microscopy slides stained with a combination of hematoxylin and eosin and elastic trichrome revealed cardiomyocyte (CM) hypertrophy, extensive myofiber disarray, trabeculation, multinucleation (more than two nuclei per myocyte), fibrosis, and thick-walled coronary arteries within the myocardium of TOF tissue. The endocardium from TOF specimens was thickened and hypercellular with prominent fibrosis and elastosis. Mitosis was not observed. At the interface between the endocardium and myocardium, the TOF specimens demonstrated myocyte dispolarity (orientation of CMs perpendicular to the endocardial surface), vascularization, and fibrosis. Immunohistochemical studies were performed using monoclonal antibodies to vimentin, desmin, muscle-specific actin (MSA), epidermal growth factor (EGF), epidermal growth factor receptor (EGFR), and laminin. Compared to the tissue from controls, TOF tissue showed a pattern of upregulated expression of epitopes within the endocardium and adjacent subendocardial myocardium. Decoration for MSA, vimentin, desmin, and EGFR highlighted the zonal nature of this tissue hyperactivity. Laminin prominently outlined endocardial cells, subendocardial CMs, and interface vessels in TOF tissue compared to the remainder of the myocardium and tissue from controls. Overall, changes in TOF were age-related, with older patients showing less zonal myocardial reactivity. These findings provide evidence for an ongoing, complex remodeling of the RVOT muscle in TOF.

"Meandering" pulmonary veins: report of a case in an asymptomatic 12-year-old girl.

We report a case of a healthy, asymptomatic 12-year-old girl in whom anomalous pulmonary venous connection to the left atrium occurred as an isolated congenital anomaly. This condition, termed "meandering" pulmonary veins, is closely related to scimitar syndrome and is usually associated with hypogenesis of the right lung and dextropositioning of the heart. To our knowledge, ours is only the second reported case of meandering pulmonary veins occurring as an isolated anomaly.