Outcome of localised blastemal-type Wilms tumour patients treated according to intensified treatment in the SIOP WT 2001 protocol, a report of the SIOP Renal Tumour Study Group (SIOP-RTSG).

Blastemal-type Wilms tumour (BT-WT) has been identified as a high risk histological subgroup in WT assessed after pre-nephrectomy chemotherapy in trials of the International Society of Paediatric Oncology (SIOP) Renal Tumour Study Group. Therefore, in SIOPWT2001, post-operative chemotherapy for BT-WT was intensified aiming to improve survival. Survival analysis of all unilateral BT-WT patients (SIOPWT2001) (n=238), was compared with historical BT-WT controls (SIOP93-01) (n=113). 351/4061 (8.6%) unilateral non-metastatic BT-WT patients (SIOP93-01/SIOPWT2001) were studied. Median age at diagnosis was 43 months (Inter Quartile Range (IQR) 24-68 months), stages: I (n=140, 40%), II (n=106, 30%), III (n=105, 30%). BT-WTs were higher staged, showed greater volume decrease after pre-operative chemotherapy and were diagnosed at an older median age compared to other WT patients. Patient characteristics did not differ substantially between SIOP93-01 and SIOPWT2001. Univariate analysis showed a 5-year event-free survival (EFS) of 80% (95% confidence interval (CI): 75-86%) (SIOPWT2001) compared to 67% in SIOP93-01 (95% CI: 59-76%; p=0.006) and overall survival (OS) of 88% (95% CI: 83-93%) (SIOPWT2001) compared to 84% (95% CI: 77-91%; p=0.4) in SIOP93-01. 95% of relapses were distant metastases (SIOP93-01/SIOPWT2001). Treatment protocol, age at diagnosis, tumour stage (III versus I/II) and volume (at surgery), were prognostic variables for EFS (uni- and multivariate Cox regression analysis). Independent prognosticators for OS were age at diagnosis, tumour stage and volume (at surgery). The most significant survival benefit of intensified treatment, was observed in Stage I (EFS 96% in SIOPWT2001 (OS 100%), 71% in SIOP93-01 (OS 90%)). BT-WT derived benefits from more intensive chemotherapy as reflected by a reduction in relapse risk. However, the benefit of the more intensive chemotherapy to improve OS was only observed in stage I BT-WTs, by adding doxorubicin.

Clear cell sarcomas of the kidney registered on International Society of Pediatric Oncology (SIOP) 93-01 and SIOP 2001 protocols: a report of the SIOP Renal Tumour Study Group.

PURPOSE: Clear Cell Sarcoma of the Kidney (CCSK) is a rare childhood renal tumour. Only a few homogeneously treated CCSK cohorts have been reported. This study aims to describe clinical characteristics and survival of CCSK patients treated according to recent International Society of Pediatric Oncology (SIOP) protocols. PATIENTS AND METHODS: We analysed the prospectively collected data of patients with a histologically verified CCSK, entered onto SIOP 93-01/2001 trials. RESULTS: A total of 191 CCSK patients (64% male) were analysed, with a median age at diagnosis of 2.6 years. Stage distribution for stages I, II, III and IV was 42%, 23%, 28% and 7%, respectively. Pre-operative chemotherapy was administered to 169/191 patients. All patients underwent total nephrectomy and 189/191 patients received post-operative chemotherapy. Radiotherapy was applied in 2/80 stage I, 33/44 stage II, 44/54 stage III and 6/13 stage IV patients. Five year event-free survival (EFS) and overall survival (OS) were 79% (95% confidence interval (CI): 73-85%) and 86% (95% CI: 80-92%) respectively. Stage IV disease and young age were significant adverse prognostic factors for event-free survival. Factors such as gender, tumour volume and type of initial treatment were not found to be prognostic for EFS and OS. CONCLUSION: In this largest SIOP cohort described so far, overall outcome of CCSK is reasonable, although treatment of young and advanced-stage disease patients is challenging. As further intensification of treatment is hampered by direct and late toxicity, future directions should include the development of targeted therapy based on specific molecular aberrations of CCSK.

Neuroblastoma cells injected into experimental mature teratoma reveal a tropism for embryonic loose mesenchyme.

Embryonic neural tumors are responsible for a disproportionate number of cancer deaths in children. Although dramatic improvements in survival for pediatric malignancy has been achieved in previous years advancements seem to be slowing down. For the development of new enhanced therapy and an increased understanding of the disease, pre-clinical models better capturing the neoplastic niche are essential. Tumors of early childhood present in this respect a particular challenge. Here, we explore how components of the embryonic process in stem­cell induced mature teratoma can function as an experimental in vivo microenvironment instigating the growth of injected childhood neuroblastoma (NB) cell lines. Three human NB cell lines, IMR-32, Kelly and SK-N-BE(2), were injected into mature pluripotent stem cell­induced teratoma (PSCT) and compared to xenografts of the same cell lines. Proliferative NB cells from all lines were readily detected in both models with a typical histology of a poorly differentiated NB tumor with a variable amount of fibrovascular stroma. Uniquely in the PSCT microenvironment, NB cells were found integrated in a non­random fashion. Neuroblastoma cells were never observed in areas with well-differentiated somatic tissue i.e. bone, muscle, gut or areas of other easily identifiable tissue types. Instead, the three cell lines all showed initial growth exclusively occurring in the embryonic loose mesenchymal stroma, resulting in a histology recapitulating NB native presentation in vivo. Whether this reflects the 'open' nature of loose mesenchyme more easily giving space to new cells compared to other more dense tissues, the rigidity of matrix providing physical cues modulating NB characteristics, or if embryonic loose mesenchyme may supply developmental cues that attracted or promoted the integration of NB, remains to be tested. We tentatively hypothesize that mature PSCT provide an embryonic niche well suited for in vivo studies on NB.

Clinical application of the multigene analysis test in discriminating between ulcerative colitis and Crohn's disease: a retrospective study.

METHODS: The newly described--multigene analysis test (DiBiCol) identifying 7 inflammatory bowel disease (IBD)-specific genes in colonic mucosal biopsy differentiating between ulcerative colitis (UC) and Crohn's disease (CD) with active inflammation--is a new addition to existing methods with a higher stated sensitivity and specificity. Method biopsy material from 78 patients with a complicated course diagnosed as most probably UC in 38, CD in 18 and inflammatory bowel disease unclassified (IBDU) in 22 were investigated by DiBiCol. RESULTS: DiBiCol showed a pattern consistent with CD in 13 patients with UC and led to change of diagnosis in 3 patients and a strong suggestion of CD in 8 patients. A total of 2 patients remained as UC. DiBiCol showed a pattern of UC in 4 patients of 18 with CD leading to a changing of diagnosis to UC in 3 patients, but the fourth remained as CD. In 22 patients with IBDU DiBiCol showed a pattern consistent with UC in 7 cases and with CD in 13 cases. A new evaluation 1 year after the DiBiCol allowed the assessment of clinical diagnosis in 10 patients confirmed in 9 of 10 patients by DiBiCol. In patients with acute flare of colitis the clinical diagnosis corresponded in 10 of 12 UC and in 5 of 6 CD cases. SUMMARY: Adopting the DiBiCol test led to a change of the primary diagnosis in a significant number of patients with the initial diagnosis of UC and CD and suggested a clinically probable diagnosis in most of the patients with IBDU and in those with an acute flare of colitis.

The pathology of Wilms' tumour (nephroblastoma): the International Society of Paediatric Oncology approach.

In the International Society of Paediatric Oncology renal tumour trials, preoperative chemotherapy has been successfully applied with resulting reduction of tumour rupture and increased favourable stage distribution of nephroblastoma. Postoperative treatment includes chemotherapy and sometimes radiotherapy in a risk-adapted approach based on histological sub-classification and stage of the tumour. However, preoperative chemotherapy alters the tumour's histological features and distribution of subtypes, and makes staging more difficult. The paper highlights the most common practical diagnostic difficulties that a pathologist is faced with in dealing with pretreated nephroblastomas. It emphasises the importance of a systematic, step-by-step analysis based on adequately sampled material, in order to accurately sub-classify a nephroblastoma as a low, intermediate or high risk tumour and assign its genuine stage. Finally, it outlines the standard operating procedure for submission of renal tumours for rapid central pathology review which allows the treating oncologists to apply the optimal treatment protocol.

Reduction of postoperative chemotherapy in children with stage I intermediate-risk and anaplastic Wilms' tumour (SIOP 93-01 trial): a randomised controlled trial.

BACKGROUND: Present treatment for Wilms' tumour is very successful. Now, efforts are aimed at reducing toxicity and burden of treatment by shortening schedules without loss of effectiveness. The objective of this randomised trial was to assess whether postoperative chemotherapy for patients with stage I intermediate-risk and anaplastic Wilms' tumour could be shortened to only 4 weeks from the standard 18 weeks, while maintaining equivalent event-free survival. METHODS: Between June, 1993, and June, 2000, 410 patients were randomly assigned after four doses of vincristine plus one course of dactinomycin postoperatively either to stop further adjuvant chemotherapy (no further chemotherapy group, n=200), or to receive a further two courses of the same chemotherapy (standard group, n=210). Previous treatment consisted of chemotherapy before nephrectomy of four doses of vincristine and two courses of dactinomycin followed by surgical resection of the tumour. Eligible patients were at least 6 months old and had stage I tumours with either intermediate-risk histology or anaplasia. The primary endpoint of this equivalence trial was 2-year event-free survival. Both per-protocol and intention-to-treat analyses were done. FINDINGS: By 2 years, 18 recurrences were reported in the standard group, and 22 in the no further chemotherapy group. Event-free survival was 91.4% (95% CI 87.5-95.2) for the no further chemotherapy group and 88.8% (84.3-93.2) for the standard group (difference=2.6%, upper 97.5% confidence limit 8.4%). The null hypothesis, that experimental treatment is less effective than standard treatment, could be rejected (p=0.008). CONCLUSIONS: Shortening duration of chemotherapy could reduce acute and late side-effects and inconvenience for patient and parents while maintaining effectiveness, and could be beneficial in terms of health costs.

Intracranial relapse in Wilms tumor patients.

BACKGROUND: In children with nephroblastoma, recurrence with metastases in the central nervous system is rare. Recently, previous reports (NWTSG and UKCCSG) reported brain metastases with an incidence of respectively 0.5% and 0.6% in Wilms tumor (WT) patients (respectively n = 30/5,852 and n = 7/1,249). PROCEDURE: We retrospectively investigated the incidence and survival of patients with central nervous system relapse in WT patients, treated according to the consecutive SIOP protocols 1, 2, 5, 6, 9, and 93-01. All children with WT from 1971 until 2000 were enrolled in the study (3,040 eligible patients). Specimens at diagnosis and if possible at relapse were centrally reviewed. Patients with renal neoplasms other than WT were excluded. RESULTS: CNS relapse was documented in 14 patients (0.5%). Median time to CNS relapse was 16 months (3-69). The occurrence of relapse was not associated with specific histological subtypes. In seven patients intracranial metastases occurred at first relapse, of which two were isolated relapses. In five patients no treatment was started because of the poor condition of the patient, the other nine cases were treated with (a combination of) chemotherapy (n = 6), surgery (n = 4), and radiotherapy (n = 6). CONCLUSIONS: CNS relapse in WNT is rare. In contrast to reports of other Wilms tumor study groups, although four patients reached (local) CR, the SIOP registry showed that eventually none of the documented WT patients survived.

Primary AL-amyloidosis, ulcerative colitis and collagenous colitis in a 57-year-old woman: a case study.

A 57-year-old woman with AL-amyloid deposits in the heart, gastrointestinal tract and the liver developed ulcerative colitis, which was treated with glucocorticosteroids and 5-aminosalicylic acid, with good response. The AL-amyloidosis was successfully treated with high-dose chemotherapy and autologous stem-cell transplantation. The patient was in good clinical condition for 18 months after treatment, until she developed diarrhea, which was found to be due to collagenous colitis. Two years after treatment of amyloidosis, the patient is in excellent condition, the symptoms of heart failure have stabilized and no adverse effects of the treatment regime have been observed. The bowel diseases are in clinical remission.

Noninvasive estimation of tumour viability in a xenograft model of human neuroblastoma with proton magnetic resonance spectroscopy (1H MRS).

The aim of the study was to evaluate proton magnetic resonance spectroscopy ((1)H MRS) for noninvasive biological characterisation of neuroblastoma xenografts in vivo. For designing the experiments, human neuroblastoma xenografts growing subcutaneously in nude rats were analysed in vivo with (1)H MRS and magnetic resonance imaging at 4.7 T. The effects of spontaneous tumour growth and antiangiogenesis treatment, respectively, on spectral characteristics were evaluated. The spectroscopic findings were compared to tumour morphology, proliferation and viable tumour tissue fraction. The results showed that signals from choline (Cho)-containing compounds and mobile lipids (MLs) dominated the spectra. The individual ML/Cho ratios for both treated and untreated tumours were positively correlated with tumour volume (P<0.05). There was an inverse correlation between the ML/Cho ratio and the viable tumour fraction (r=-0.86, P<0.001). Higher ML/Cho ratios concomitant with pronounced histological changes were seen in spectra from tumours treated with the antiangiogenic drug TNP-470, compared to untreated control tumours (P<0.05). In conclusion, the ML/Cho ratio obtained in vivo by (1)H MRS enabled accurate assessment of the viable tumour fraction in a human neuroblastoma xenograft model. (1)H MRS also revealed early metabolic effects of antiangiogenesis treatment. (1)H MRS could prove useful as a tool to monitor experimental therapy in preclinical models of neuroblastoma, and possibly also in children.

Physical activity increases bone size in prepubertal boys and bone mass in prepubertal girls: a combined cross-sectional and 3-year longitudinal study.

This study evaluates the effect on the skeleton of physical activity from age 9 to 16. In 42 girls and 44 boys, bone mass and bone size were evaluated longitudinally by dual-energy X-ray absorptiometry (DXA) from ages 13 to 16. Physical activity from ages 9 to 13 was cross-sectionally evaluated at baseline (age 13). Girls with high physical activity from ages 9 to 13 at baseline had higher femoral neck bone mineral content (FN BMC; g) (P = 0.07), higher FN areal bone mineral density (FN aBMD; g/cm2), and higher FN volumetric BMD (FN vBMD; g/cm3) (both P < 0.05) compared with girls of low activity. FN width (cm) and head aBMD (an unloaded region) showed no differences when comparing the two groups. Three years of further high and low activity (from ages 13 to 16) did not yield any increased differences between the two groups. Boys with high physical activity from ages 9 to 13, had at baseline higher FN BMC, FN aBMD, and FN width (all P < 0.05) compared with boys with low activity. FN vBMD and head aBMD showed no differences when comparing the two groups. Three years of further high and low activity did not yield any increased differences between the two groups. We conclude that exercise may yield skeletal benefits before age 13, and that 3 years of continued high or low level activity up to age 16 did not yield any increased differences in bone size or bone mass in either girls or boys.

IgE is expressed on, but not produced by, fetal cells in the human placenta irrespective of maternal atopy.

The prevalence of atopic diseases in children has increased during the last decades. Atopic symptoms usually appear early in life. This implies an early priming for atopic disease, possibly even at the fetal level. We therefore compared the presence and production of IgE in the local in utero environment during pregnancy in atopic and non-atopic women. Eighty-six women were included in the study. Fifty women were demonstrated to be atopics, based on clinical symptoms of atopic disease together with a positive Phadiatop and/or skin prick test. Placentas from these term pregnancies were obtained. Slices covering the full thickness of the placenta were cut clockwise around the umbilical cord and were analysed with immunohistochemistry. Surprisingly, numerous IgE+ cells, located primarily in the fetal villous stroma, were detected in a majority of the investigated placentas irrespective of the atopy of the mother or maternal or fetal total serum IgE levels. The placental IgE could not be demonstrated to be bound to IgE receptors, but was shown to be bound to fetal macrophages, possibly via FcgammaRI. No evidence was found for local fetal IgE production, although cells producing epsilon transcripts were occasionally detected in the decidua. We describe here the novel finding of numerous IgE+ cells in the human placenta, suggesting an hitherto unknown role for IgE in a successful pregnancy outcome, irrespective of whether or not the mother is atopic.

Bidirectional defibrillation using implantable defibrillators: a prospective randomized comparison between pectoral and abdominal active generators.

The objective of this study was to compare the effects of active abdominal and pectoral generator positions on DFTs in a bidirectional tripolar ICD system. Twenty-five consecutive patients had ICD systems implanted under general anesthesia. A transvenous single lead bipolar defibrillation system and an active 57-cc test emulator in the abdominal and pectoral positions were used in the same patient. A randomized, alternating step-down protocol was used starting at 15 J with 3-J decrements until failure. The mean implantation time was 114 +/- 23 minutes, the mean arrhythmia duration was 14.5 +/- 1.5 seconds, and the mean recovery time was 5.4 +/- 1.1 minutes. The mean DFTs in the abdominal and pectoral positions were 10.9 +/- 5.1 and 9.7 +/- 5.2 J, respectively (NS), the mean intraindividual DFT difference (abdominal minus pectoral) was -0.89 +/- 4.15 J (range -9.5 to 8 J). The 95% confidence interval showed a -2.60 to +0.82 J mean difference (NS). The DFT was < 15 J in 72% and 88% of the patients and the defibrillation impedance was 41 +/- 3 and 44 +/- 3 omega, abdominal versus pectoral positions. There was no difference in DFT between active abdominal and pectoral generator bidirectional tripolar defibrillation. The pectoral position may be considered the primary option, but in cases of high DFTs the abdominal site should be considered an alternative to adding a subcutaneous patch. In some patients, the anatomy may favor an abdominal position. Possible differences in the long-term functionality on the leads are not yet well known and need to be further evaluated.

Methylation changes in the human IGF2 p3 promoter parallel IGF2 expression in the primary tumor, established cell line, and xenograft of a human hepatoblastoma.

Hepatoblastoma (HB) is a rare malignant embryonal liver tumor. Its pathogenesis has been associated with altered regulation of the IGF2 and H19 genes, and previous studies have suggested a correlation between abnormal methylation and altered expression of these genes in hepatoblastoma. Upregulation of the activity of the IGF2 promoter P3 has previously been shown to be tightly correlated with demethylation in hepatoblastoma. Here, we have used bisulfite genomic sequencing to characterize the methylation pattern of the IGF2 promoter P3 in the hepatoblastoma-derived cell line Hep T1, in the original tumor from which Hep T1 is derived, and in nude mouse xenografts of the Hep T1 cell line. The results show a clear difference in methylation pattern of the most proximal region of the IGF2 P3 promoter between the primary tumor, the cell line, and the xenografts. RNase protection and mRNA in situ hybridization revealed that variations in methylation patterns was paralleled by the levels of IGF2 P3 mRNA, which was detectable in the primary tumor and xenografts, but not in the cell line. Furthermore, it was demonstrated that H19 was reactivated and demethylated in the HepT1 cell line by 5-azaCytidine, in contrast to IGF2 P3, which was not demethylated or reactivated. We suggest that methylation of the proximal IGF2 P3 is important for its regulation.

Evidence of chromaffin oxygen sensing in neuroblastoma.

With the aid of IGF2 and VEGF in situ hybridization; tyrosine hydroxylase, chromogranin A, and Ki67 immunohistochemistry; and TUNEL staining applied to a large series of clinical neuroblastomas and to an animal model, we show here that stroma-poor neuroblastomas show evidence of chromaffin differentiation similar to that of type 1 small intensely fluorescent (SIF) cells and that this occurs in a vascular-dependent fashion, indicating a role for local tumor hypoxia in the differentiation process.

p53 mutations in urinary bladder cancer.

We have screened for mutations in exons 5-8 of the p53 gene in a series consisting of 189 patients with urinary bladder neoplasms. 82 (44%) neoplasms were lowly malignant (Ta, G1-G2a) and 106 (56%) were highly malignant (G2b-G4 or > or = T1). Only one mutation was in a lowly malignant urinary bladder neoplasm, in total we found p53 mutations in 26 (14%) of the 189 patients. 30% of the samples had loss of heterozygosity (LOH) for one or both of the p53 exogenic (CA)n repeat and the p53 intragenic (AAAAT)n repeat markers. 31 samples (21%) showed LOH but were not mutated, suggesting other mechanisms inactivating p53 than mutations. 4 mutations were found at codon 280 and 2 mutations were found at codon 285, 2 previously reported hot spots for urinary bladder cancer. The study indicate a boundary between G2a and G2b tumours concerning the occurrence of genetic events affecting p53 function; moderately differentiated (G2) urinary bladder neoplasms probably are genetically heterogeneous which supports the suggestion that they should not be grouped together but instead, for example, be categorized as either lowly or highly malignant.

Angiogenesis and angiogenic growth factors in Wilms tumor.

PURPOSE: Angiogenesis, that is new blood vessel formation, is a prerequisite for growth and metastasis of solid tumors. This study was undertaken to quantify tumor capillaries, investigate immunohistochemical expression and measure serum concentrations of angiogenic growth factors in patients with Wilms tumor. MATERIALS AND METHODS: The hospital records of 33 patients were reviewed and new slides were stained for the endothelial cell marker CD31. Capillaries were quantified in the most vascularized part of the tumor (hot spot) and in the whole slide. New slides were stained immunohistochemically for the angiogenic growth factors angiogenin, basic fibroblast growth factor (bFGF), transforming growth factor alpha, transforming growth factor beta1-3, tumor necrosis factor alpha and vascular endothelial growth factor (VEGF), and their immunoreactivity was quantified. Pretreatment serum samples from 14 patients and 56 healthy control children were analyzed using enzyme-linked immunosorbent assay kits for angiogenin, basic fibroblast growth factor, epidermal growth factor, hepatocyte growth factor, tumor necrosis factor alpha and VEGF. RESULTS: Logistic regression analysis and Kaplan-Meier estimates showed that quantifications based on the tumor hot spot had a significant impact on survival probability (p <0.05). The tumor hot spot counts were highest in the blastemal compartment. Levels of hepatocyte growth factor and VEGF in serum were 3 times higher than those in controls (p <0.01). CONCLUSIONS: Although the sample size is small in this study, the results imply that angiogenesis in Wilms tumor is driven by angiogenic growth factors, and that intratumoral capillary quantification and determinations of serum levels of angiogenic growth factors may be of clinical value.

Peripubertal moderate exercise increases bone mass in boys but not in girls: a population-based intervention study.

On the basis of cross-sectional studies in elite athletes and longitudinal studies, physical activity in growing children has been suggested to enhance bone mineral acquisition and prevent osteoporosis later in life. The level of exercise in most of these studies is not applicable in a population on a day-to-day basis. The aim of this study was to determine whether moderate increased exercise within the school curriculum from age 12 to 16 years would have anabolic bone effects. In a population-based setting of 40 boys and 40 girls the school curriculum was enhanced to physical education 4 times per week for 3-4 years. Controls were 82 boys and 66 girls who had had physical education twice a week over a corresponding period. Both cases and controls were measured at age 16 years. Bone mineral content (BMC), areal bone mineral density (aBMD), bone size (femoral neck width) and volumetric BMD (vBMD) were measured in total body, spine and femoral neck (FN) by dual-energy X-ray absorptiometry. Data are presented as mean +/- SD. BMC (8 +/- 15%, p = 0.04), aBMD (9 +/- 13%, p = 0.002) and vBMD (9 +/- 15%, p = 0.001) were all higher in FN in the male intervention group compared with controls. FN bone size was no higher in the intervention group than in the controls. In girls, no differences were found when comparing the intervention group with controls. The results remained after adjusting for confounding factors such as weight, height, milk intake and activity after school. In summary, we report that increased bone mass can be achieved in a population-based cohort of boys (but not in girls) by moderate increased physical activity within the school curriculum from age 12 to 16 years. We speculate that the same results can be seen in girls if intervention starts at an earlier age. We conclude that increasing the physical education content of the Swedish school curriculum may improve bone mass in at least peripubertal boys.

Presence of CD30(+) and CD30L(+) cells in human placenta and soluble CD30 levels in cord blood are independent of maternal atopy.

The intrauterine environment is characterized by a Th2 dominance during pregnancy, a milieu that also promotes atopic allergy. The aim of this study was to compare the presence of CD30, a molecule associated with Th2 related disorders such as atopic allergy, and its ligand (CD30L) in placenta in order to investigate if the placenta environment differs between atopic and non-atopic women. Serum concentrations of soluble CD30 (sCD30) from the mothers and their newborns were also elucidated. There were no differences in the immunohistochemical expression of CD30 and CD30L in placenta from atopic (n=28) compared with non-atopic (n=37) women. CD30 was expressed on the decidual stromal cells alone, while CD30L, previously not described in placenta, was detected on macrophage-like HLA-DR(+) cells throughout the mesenchymal chorionic villi. Serum sCD30 in atopic mothers was significantly elevated compared with serum sCD30 in non-atopic mothers (P< 0.05), while sCD30 levels in cord blood were similar in both groups independently of maternal atopic heredity. We suggest that sCD30 in cord blood and CD30 expression by decidual cells may reflect the Th2 environment surrounding the fetus, and both CD30 and CD30L could have immune regulatory functions in placenta.

Pulmonary abnormalities at long-term follow-up of patients with Langerhans cell histiocytosis.

BACKGROUND: In Langerhans cell histiocytosis (LCH) pulmonary involvement, which is often initially asymptomatic, may contribute to significant morbidity and mortality. To determine the long-term prognosis, a cross-sectional study was undertaken. PROCEDURE: Forty-one patients with > or = 5 years follow-up after the diagnosis of LCH were interviewed and underwent physical examination, blood tests, a chest X-ray and a high-resolution CT (HRCT) of the lungs. All patients included had been referred to the Department of Pediatrics at the Karolinska Hospital in Stockholm between July 1962 and February 1990 (median follow-up 16 years). Biopsies from all patients were reviewed and confirmed to be consistent with LCH. Information on previous clinical features including treatment and the results of chest X-rays were also collected for risk factor analysis. RESULTS: Radiographic abnormalities of the lungs (cysts and/or emphysema), found in 10/41 (24%) at follow-up, were classified into five groups according to the extent of the cysts. These patients had more often suffered from multisystem than from single-system disease (P = 0.01), were significantly older at diagnosis (P < 0.001), and had been more heavily treated with chemotherapy and/or radiotherapy. They were also more frequently smokers (P < 0.0001) and 7/10 (70%) had suffered lung involvement at diagnosis. At the time of diagnosis of the pulmonary involvement, 4/10 (40%) patients had respiratory symptoms, but only 2/10 (20%) had symptoms at follow-up. CONCLUSIONS: Ten (24%) of the 41 patients had abnormal findings on radiological examination of the lungs at long-term follow-up and seven are or had been smokers. It is of great importance that patients with LCH be informed about smoking-related pulmonary morbidity. Prolonged monitoring of the lungs for smokers and patients with known pulmonary involvement is recommended.