ABSTRACT
Pyogenic flexor tenosynovitis is a frequent and serious condition. However, there is no consensus on the use of antibiotics. The objective of our study was to describe the treatment of this condition and to identify the surgical and medical management parameters to propose an effective and consensual postoperative antibiotic therapy protocol. We retrospectively reviewed pyogenic flexor tenosynovitis of the thumb or fingers treated between 01/01/2013 and 01/01/2018 at a teaching hospital. Inclusion criteria were confirmation of the clinical diagnosis intraoperatively and a minimum post-antibiotic follow-up of 6 months. Comorbidities, type of surgery, antibiotic therapy parameters, and treatment outcome were assessed. One hundred and thirteen patients were included. Fifty-four percent had comorbidities. The most frequent germ was staphylococcus, all patients received postoperative antibiotic therapy. Intravenous or intravenous followed by oral administration did not provide any benefit compared to an exclusively oral treatment (p = 0.46). The duration of postoperative antibiotic therapy (less than 7 days, between 7 and 14 days or more than 14 days) did not lead to any difference in healing rate (p = 0.67). However, treating for less than 7 days versus 7-14 days seemed to be associated with a higher risk of failure, although not statistically significant. Oral postoperative antibiotic therapy with amoxicillin + clavulanic acid for 7-14 days appears to be effective, allowing for outpatient management.
Subject(s)
Tenosynovitis , Amoxicillin-Potassium Clavulanate Combination/therapeutic use , Anti-Bacterial Agents/therapeutic use , Fingers/surgery , Humans , Retrospective Studies , Tenosynovitis/drug therapyABSTRACT
Survival for subgroups of patients with Wilms tumor (WT), such as those who suffer from relapse, is disappointing. Some patients' treatment plans include high-dose chemotherapy (HDT) with autologous hematopoietic cell transplantation (aHCT), although proof for its benefit is lacking. To increase the level of evidence regarding children with WT receiving aHCT as consolidation of first or second remission (after first relapse), we extracted relevant data from the European Blood and Marrow Transplantation Registry concerning 69 patients. Different HDT regimens were administered, mostly either melphalan-containing (n = 34) or thiotepa-containing (n = 14). For the whole population, 5-year overall survival (OS) and event-free survival (EFS) probabilities were 0.67 (±0.06) and 0.63 (±0.06), respectively (median observation time 7.8 years); for children transplanted in first remission, OS and EFS were 0.69 (±0.09) and 0.72 (±0.08). In univariate analysis, male gender and relapse in multiple sites were associated with lower OS probabilities. The use of a given pretransplant regimen (i.e. melphalan alone versus regimens with multiple drugs) did not seem to influence EFS/OS probability after aHCT, but significantly influenced platelet engraftment (more delayed with thiotepa). We here provide further data to improve the basis for future evidence-based clinical decision-making when using HDT and aHCT in relapsed/refractory WT.
Subject(s)
Hematopoietic Stem Cell Transplantation , Kidney Neoplasms , Wilms Tumor , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Bone Marrow , Child , Combined Modality Therapy , Humans , Male , Melphalan , Neoplasm Recurrence, Local , Transplantation, Autologous , Treatment Outcome , Wilms Tumor/therapyABSTRACT
OBJECTIVES: According to the Renal Tumor Study Group (RTSG) of the International Society of Paediatric Oncology (SIOP), diagnostic biopsy of renal tumors prior to neoadjuvant chemotherapy is not mandatory unless the presentation is atypical for a Wilms tumor (WT). This study addresses the relevance of this strategy as well as the accuracy and safety of image-guided needle biopsy. METHODS: Clinical, radiological, and pathological data from 317 children (141 males/176 females, mean age: 4 years, range, 0-17.6) consecutively treated in one SIOP-affiliated institution were retrospectively analyzed. RESULTS: Presumptive chemotherapy for WT was decided for 182 patients (57% of the cohort), 24 (8%) were operated upfront, and 111 (35%) were biopsied at diagnosis. A non-WT was confirmed after surgery in 5/182 (3%), 11/24 (46%), and 28/111 (25%), respectively. Age at diagnosis was the most commonly (46%) used criterion to go for biopsy but a nine-year threshold should be retrospectively considered more relevant. Tumor volumes of clear cell sarcoma of the kidney and WT were significantly higher than those of other tumors (P = 0.002). The agreement between core-needle biopsy (CNB) and final histology was 99%. No significant morbidity was associated with CNB. CONCLUSION: The use of SIOP criteria to identify patients eligible for presumptive WT neoadjuvant chemotherapy or upfront surgery avoided biopsy in 65% of children and led to a 97% rate of appropriate preoperative chemotherapy. Image-guided CNB is a safe and accurate diagnostic procedure. The relevance of SIOP biopsy criteria might be improved by using an older age threshold (9 years instead of 6 years) and by adding initial tumor volume.
Subject(s)
Carcinoma, Renal Cell/diagnosis , Guidelines as Topic , Kidney Neoplasms/diagnosis , Patient Selection , Wilms Tumor/diagnosis , Adolescent , Biopsy , Carcinoma, Renal Cell/surgery , Child , Child, Preschool , Diagnosis, Differential , Female , Follow-Up Studies , Humans , Infant , Infant, Newborn , Kidney Neoplasms/surgery , Male , Neoadjuvant Therapy , Neoplasm Staging , Prognosis , ROC Curve , Retrospective Studies , Wilms Tumor/surgeryABSTRACT
INTRODUCTION: According to the European Society of Pediatric Oncology (SIOPE) standard of care guidelines, high-quality care of children and adolescents with cancer needs to be delivered by well-trained multidisciplinary teams in specialist centers working with designated shared-care local centers in a so-called hub-and-spoke model. The Diplôme Inter-Universitaire d'Oncologie Pédiatrique (DIUOP) is the only European training program in pediatric oncology in French for all physicians involved in care of patients with pediatric malignancies. In agreement with the SIOPE syllabus, the DIUOP is composed of training courses (120h), on-site practical training in a specialist center, and a research project to be defended before an examining board. METHOD: All graduates received a questionnaire to describe their current professional position. A comprehensive PubMed analysis retrieved all papers published form DIUOP research projects. RESULTS: From 2000 to 2011, 290 physicians were trained: 242 pediatricians, 21 surgeons, and 19 radiation therapists. Eight had another specialty including imaging, hematology, and pathology. Ninety-two were initially trained outside of France: 50% in Europe (mainly in Italy, Belgium, and Switzerland), 42% in Africa and the Middle East, and 8% in South America. Of the 266 graduates, 74% answered the questionnaire, and 90% of them take care of children and adolescents with cancer. Sixty-nine articles, i.e., one out of four research projects, were published in 34 journals with a median impact factor of 3.5 (0-22.6), 85% in English. CONCLUSION: DIUOP is the only French-speaking European education program providing a high-quality, professionalizing, and comprehensive multidisciplinary training program for French and international specialists taking care of children and adolescents with cancer.
Subject(s)
Hematology/education , Medical Oncology/education , Pediatrics/education , Adolescent , Child , France , Humans , Interdisciplinary Communication , Neoplasms/therapy , Surveys and QuestionnairesABSTRACT
Prostatic laser vaporization resection is a new and fast growing technique. Most publications compare this technique to the standard diathermic snare prostate resection without considering its particular complications. Septic arthritis of the trapezio-metacarpal joint is particularly rare if it has a haematogenous origin. We present here the case of a 65-year-old man with an isolated trapezio-metacarpal Pseudomonas aeruginosa arthritis with a haematogenous origin following a laser vaporization prostate resection.
Subject(s)
Arthritis, Infectious/etiology , Laser Therapy/adverse effects , Osteoarthritis/etiology , Prostate/surgery , Pseudomonas Infections/etiology , Pseudomonas aeruginosa , Aged , Arthritis, Infectious/diagnosis , Humans , Male , Osteoarthritis/diagnosis , Pseudomonas Infections/diagnosisABSTRACT
The purpose of this investigation was to evaluate the microbiological diagnosis yield of post-biopsy blood cultures (PBBCs) and second percutaneous needle biopsy (PNB) following an initial negative biopsy in vertebral osteomyelitis (VO) without bacteremia. A retrospective multicenter study was performed. Patients with VO, pre-biopsy negative blood culture(s), ≥1 PNB, and ≥1 PBBC (0-4 h) were included. One hundred and sixty-nine PNBs (136 first and 33 following initial negative biopsy) were performed for 136 patients (median age = 58 years, sex ratio M/F = 1.9). First and second PNBs had a similar yield: 43.4 % (59/136) versus 39.4 % (13/33), respectively. Only two PBBCs (1.1 %) led to a microbiological diagnosis. The strategy with positive first PNB and second PNB following an initial negative result led to microbiological diagnosis in 79.6 % (74/93) of cases versus 44.1 % (60/136) for the strategy with only one biopsy. In the multivariate analysis, young age (odds ratio, OR [95 % confidence interval (CI)] = 0.98 [0.97; 0.99] per 1 year increase, p = 0.02) and >1 sample (OR = 2.4 ([1.3; 4.4], p = 0.007)) were independently associated with positive PNB. To optimize microbiological diagnosis in vertebral osteomyelitis, performing a second PNB (after an initial negative biopsy) could lead to a microbiological diagnosis in nearly 80 % of patients. PBBC appears to be limited in microbiological diagnosis.
Subject(s)
Osteomyelitis/diagnosis , Spinal Diseases/diagnosis , Aged , Bacteremia/diagnosis , Bacteremia/microbiology , Bacteremia/pathology , Biopsy/methods , Female , Humans , Male , Middle Aged , Osteomyelitis/microbiology , Osteomyelitis/pathology , Retrospective Studies , Spinal Diseases/microbiology , Spinal Diseases/pathologyABSTRACT
BACKGROUND: Wilms Tumor (WT) can occur in association with tumor predisposition syndromes and/or with clinical malformations. These associations have not been fully characterized at a clinical and molecular genetic level. This study aims to describe clinical malformations, genetic abnormalities, and tumor predisposition syndromes in patients with WT and to propose guidelines regarding indications for clinical and molecular genetic explorations. PROCEDURE: This retrospective study analyzed clinical abnormalities and predisposition syndromes among 295 patients treated for WT between 1986 and 2009 in a single pediatric oncological center. RESULTS: Clinically identified malformations and predisposition syndromes were observed in 52/295 patients (17.6%). Genetically proven tumor predisposition syndromes (n = 14) frequently observed were syndromes associated with alterations of the chromosome WT1 region such as WAGR (n = 6) and Denys-Drash syndromes (n = 3), syndromes associated with alterations of the WT2 region (Beckwith-Wiedeman syndrome, n = 3), and Fanconi anemia (n = 2). Hemihypertrophy and genito-urinary malformations (n = 12 and n = 16, respectively) were the most frequently identified malformations. Other different syndromes or malformations (n = 10) were less frequent. Median age of WT diagnosis was significantly earlier for children with malformations than those without (27 months vs. 37 months, P = 0.0009). There was no significant difference in terms of 5-year EFS and OS between WT patients without or with malformations. CONCLUSIONS: The frequency of malformations observed in patients with WT underline the need of genetic counseling and molecular genetic explorations for a better follow-up of these patients, with a frequently good outcome. A decisional tree, based on clinical observations of patients with WT, is proposed to guide clinicians for further molecular genetic explorations.
Subject(s)
Abnormalities, Multiple , Wilms Tumor/complications , Wilms Tumor/genetics , Child , Child, Preschool , Female , Genetic Predisposition to Disease , Humans , Male , Retrospective Studies , Syndrome , Wilms Tumor/mortalitySubject(s)
Community-Acquired Infections/microbiology , Endocarditis, Bacterial/microbiology , Methicillin-Resistant Staphylococcus aureus/isolation & purification , Staphylococcal Infections/microbiology , Adult , Anti-Bacterial Agents/therapeutic use , Bacterial Typing Techniques , Communicable Diseases, Emerging/microbiology , Community-Acquired Infections/diagnosis , Community-Acquired Infections/drug therapy , Community-Acquired Infections/epidemiology , Endocarditis, Bacterial/diagnosis , Endocarditis, Bacterial/drug therapy , Endocarditis, Bacterial/epidemiology , Female , Gastrectomy , Genes, Bacterial , Gentamicins/therapeutic use , Humans , Lymphoma, B-Cell, Marginal Zone/radiotherapy , Lymphoma, B-Cell, Marginal Zone/surgery , Methicillin-Resistant Staphylococcus aureus/classification , Methicillin-Resistant Staphylococcus aureus/genetics , Mitral Valve Insufficiency/complications , Multiple Sclerosis/complications , Neoplasms, Second Primary/diagnosis , Ovarian Neoplasms/complications , Ovarian Neoplasms/diagnosis , Postoperative Complications/diagnosis , Postoperative Complications/drug therapy , Postoperative Complications/epidemiology , Postoperative Complications/microbiology , Rifampin/therapeutic use , Staphylococcal Infections/diagnosis , Staphylococcal Infections/drug therapy , Staphylococcal Infections/epidemiology , Stomach Neoplasms/radiotherapy , Stomach Neoplasms/surgery , Vancomycin/therapeutic useABSTRACT
PURPOSE: To determine the association of clinical outcomes with the adherence to Infectious Diseases Consultation (IDC) recommendations. METHODS: From March to August 2009, all patients hospitalized in our hospital, for whom an IDC was requested, were prospectively enrolled. The adherence to recommendations was ascertained after 72 h from the IDC. The primary objective of the study was to evaluate the clinical cure rate 1 month after the IDC, according to the adherence to IDC recommendations. RESULTS: An IDC was requested for 258 inpatients. The infectious disease (ID) was most often non-severe (66%), community-acquired (62%), and already under treatment (47%). IDC proposals were most often formulated via a formal consultation (57%). Physicians' adherence to IDC recommendations was 87% for diagnostic tests and 90% for antibiotherapy. In the multivariate analysis, severe infections and direct consultation were independently associated with increased odds of adherence to recommendations for performing diagnostic tests (odds ratios 5.4 and 4.0, respectively). The overall clinical cure rate was 84% and this did not differ according to the adherence to IDC recommendations for diagnostic tests (84.3 vs. 71.4%, p = 0.15) and antimicrobial treatment (84.8 vs. 77.8%, p = 0.34). CONCLUSIONS: Some limitations of the study may explain the lack of evidence of a clinical benefit, such as the very high level of adherence to IDC recommendations and the low proportion of severe infections. However, clinical improvement was always better when recommendations were followed. Therefore, further larger randomized multicentric studies including more patients suffering from more severe IDs may be needed in order to demonstrate a clinical impact.
Subject(s)
Communicable Diseases/diagnosis , Communicable Diseases/therapy , Infectious Disease Medicine/methods , Referral and Consultation/statistics & numerical data , Adolescent , Adult , Aged , Aged, 80 and over , Analysis of Variance , Child , Child, Preschool , Female , Humans , Male , Middle Aged , Multivariate Analysis , Patient Compliance/statistics & numerical data , Prospective Studies , Treatment OutcomeABSTRACT
BACKGROUND: In neuroblastoma (NB), the presence of segmental chromosome alterations (SCAs) is associated with a higher risk of relapse. METHODS: In order to analyse the role of SCAs in infants with localised unresectable/disseminated NB without MYCN amplification, we have performed an array CGH analysis of tumours from infants enrolled in the prospective European INES trials. RESULTS: Tumour samples from 218 out of 300 enroled patients could be analysed. Segmental chromosome alterations were observed in 11%, 20% and 59% of infants enroled in trials INES99.1 (localised unresectable NB), INES99.2 (stage 4s) and INES99.3 (stage 4) (P<0.0001). Progression-free survival was poorer in patients whose tumours harboured SCA, in the whole population and in trials INES99.1 and INES99.2, in the absence of clinical symptoms (log-rank test, P=0.0001, P=0.04 and P=0.0003, respectively). In multivariate analysis, a SCA genomic profile was the strongest predictor of poorer progression-free survival. CONCLUSION: In infants with stage 4s MYCN-non-amplified NB, a SCA genomic profile identifies patients who will require upfront treatment even in the absence of other clinical indication for therapy, whereas in infants with localised unresectable NB, a genomic profile characterised by the absence of SCA identifies patients in whom treatment reduction might be possible. These findings will be implemented in a future international trial.
Subject(s)
Chromosome Aberrations , Neuroblastoma/pathology , Nuclear Proteins/genetics , Oncogene Proteins/genetics , Humans , Infant , N-Myc Proto-Oncogene Protein , Neuroblastoma/genetics , Prognosis , Prospective Studies , Recurrence , Survival AnalysisABSTRACT
BACKGROUND: Neuroblastoma is an embryonic tumour of the sympathetic nervous system, metastatic in half of the patients at diagnosis, with a high preponderance of osteomedullary disease, making accurate evaluation of metastatic sites and response to therapy challenging. Metaiodobenzylguanidine (mIBG), taken into cells via the norepinephrine transporter, provides a sensitive and specific method of assessing tumour in both soft tissue and bone sites. The goal of this report was to develop consensus guidelines for the use of mIBG scans in staging, response assessment and surveillance in neuroblastoma. METHODS: The International Neuroblastoma Risk Group (INRG) Task Force, including a multidisciplinary group in paediatric oncology of North and South America, Europe, Oceania and Asia, formed a subcommittee on metastatic disease evaluation, including expert nuclear medicine physicians and oncologists, who developed these guidelines based on their experience and the medical literature, with approval by the larger INRG Task Force. RESULTS: Guidelines for patient preparation, radiotracer administration, techniques of scanning including timing, energy, specific views, and use of single photon emission computed tomography are included. Optimal timing of scans in relation to therapy and for surveillance is reviewed. Validated semi-quantitative scoring methods in current use are reviewed, with recommendations for use in prognosis and response evaluation. CONCLUSIONS: Metaiodobenzylguanidine scans are the most sensitive and specific method of staging and response evaluation in neuroblastoma, particularly when used with a semi-quantitative scoring method. Use of the optimal techniques for mIBG in staging and response, including a semi-quantitative score, is essential for evaluation of the efficacy of new therapy.
Subject(s)
3-Iodobenzylguanidine , Bone Neoplasms/secondary , Iodine Radioisotopes , Neuroblastoma/diagnostic imaging , Soft Tissue Neoplasms/secondary , Advisory Committees , Bone Neoplasms/diagnostic imaging , Bone Neoplasms/pathology , Child , Female , Humans , Neoplasm Metastasis/diagnostic imaging , Neoplasm Metastasis/pathology , Neoplasm Staging/methods , Neuroblastoma/pathology , Practice Guidelines as Topic , Radiation Injuries/epidemiology , Radiation Injuries/prevention & control , Radiographic Image Enhancement , Radiopharmaceuticals , Soft Tissue Neoplasms/diagnostic imaging , Soft Tissue Neoplasms/pathology , Tomography, Emission-Computed, Single-Photon/methodsSubject(s)
Actinomycetales Infections/microbiology , Bronchitis/microbiology , Micrococcaceae/isolation & purification , Actinomycetales Infections/drug therapy , Acute Disease , Aged , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/therapeutic use , Bronchitis/drug therapy , Humans , Male , Microbial Sensitivity Tests , Micrococcaceae/drug effectsABSTRACT
Total body irradiation (TBI) can cause short stature because of decreased growth hormone (GH) and skeletal abnormalities. To evaluate the plasma concentrations of markers of bone formation (osteocalcin and procollagen type 1 amino-terminal propeptide, P1NP) and resorption (carboxy-terminal telopeptide, CTX), in patients (n=65) who had been given TBI at 6.6+/-0.4 years were evaluated at 9.8+/-0.4 years. Patients given single 10 Gy or fractionated 12 Gy TBI had similar characteristics, except that plasma insulin-like growth factor (IGF-1) was lower in those given a single 10 Gy. Seven had lower osteocalcin and two had higher CTX than controls. Bone markers (as zs) were positively correlated (osteocalcin with P1NP, rho=0.42, P=0.0007; osteocalcin with CTX, rho=0.3, P<0.02), but not P1NP with CTX. Plasma osteocalcin and CTX were also positively correlated with plasma IGF-1, but not with growth rate during the first year on GH (n=28). Adult height was -2.5+/-0.2 s.d.s. (n=49). Those irradiated when young (P=0.0002) or given single TBI lost more height between TBI and adult height. Most TBI patients had normal bone formation and resorption markers. Thus, impaired bone turnover is probably not the cause of their short stature and poor response to GH.
Subject(s)
Bone and Bones/metabolism , Bone and Bones/radiation effects , Whole-Body Irradiation/adverse effects , Biomarkers/blood , Body Height/drug effects , Body Height/radiation effects , Bone Development/radiation effects , Bone Remodeling/drug effects , Bone Remodeling/radiation effects , Bone and Bones/drug effects , Case-Control Studies , Child , Collagen Type I/blood , Growth Disorders/blood , Growth Disorders/etiology , Hematopoietic Stem Cell Transplantation , Human Growth Hormone/therapeutic use , Humans , Osteocalcin/blood , Peptide Fragments/blood , Peptides/blood , Procollagen/blood , Recombinant Proteins/therapeutic useABSTRACT
Main objective of this study was to confirm that surgery alone is an effective and safe treatment for localised resectable neuroblastoma except stage 2 with amplified MYCN gene (MYCNA). Of 427 eligible stages 1-2 patients, 411 had normal MYCN and 16 had MYCNA. Of the 288 stage 1 patients with normal MYCN, 1 died of complications and 16 relapsed, 2 of whom died; 5-year relapse-free survival (RFS) and overall survival (OS) rates were 94.3% (95% confidence interval (CI): 91.6-97) and 98.9% (95% CI: 97.7-100), respectively. Of the 123 stage 2 patients with normal MYCN, 1 died of sepsis and 22 relapsed, 8 of whom died (RFS 82.8%, 95% CI: 76.2-89.5; OS 93.2%, 95% CI: 88.7-97.8). In stage 2, OS and RFS were worse for patients with elevated LDH and unfavourable histopathology. Of 16 children with MYCNA, 7 were stage 1 (5 relapses and 4 deaths) and 9 were stage 2 (3 relapses and 2 deaths) patients. In conclusion, surgery alone yielded excellent OS for both stage 1 and 2 neuroblastoma without MYCNA, although stage 2 patients with unfavourable histopathology and elevated LDH suffered a high number of relapses. Both stage 1 and 2 patients with MYCNA were at greater risk of relapse.
Subject(s)
Neuroblastoma/surgery , Disease Progression , Disease-Free Survival , Europe , Female , Genes, myc , Humans , Infant , Infant, Newborn , Male , Neuroblastoma/genetics , Prognosis , Recurrence , Survival RateABSTRACT
Whereas neuroblastoma (NB) with MYCN amplification presents a poor prognosis, no single marker allows to reliably predict outcome in tumours without MYCN amplification. We report here an extensive analysis of 147 NB samples at diagnosis, without MYCN amplification, by chromosomal comparative genomic hybridisation (CGH), providing a comprehensive overview of their genomic imbalances. Comparative genomic hybridisation profiles showed gains or losses of entire chromosomes (type 1) in 71 cases, whereas partial chromosome gains or losses (type 2), including gain involving 17q were observed in 68 cases. Atypical profiles were present in eight cases. A type 1 profile was observed more frequently in localised disease (P<0.0001), and in patients of less than 12 months at diagnosis (P<0.0001). A type 2 genomic profile was associated with a higher risk of relapse in the overall population (log-rank test; P<0.0001), but also in the subgroup of patients with localised disease (log-rank test, P=0.007). In multivariate analysis, the genomic profile was the strongest independent prognostic factor. In conclusion, the genomic profile is of prognostic impact in patients without MYCN amplification, making it a help in the management of low-stage NB. Further studies using higher-resolution CGH are needed to better characterise atypical genomic alterations.
Subject(s)
Gene Amplification , Neoplasm Recurrence, Local/epidemiology , Neuroblastoma/genetics , Neuroblastoma/mortality , Nuclear Proteins/genetics , Oncogene Proteins/genetics , Chromosomes, Human/genetics , Female , Humans , Infant , Male , N-Myc Proto-Oncogene Protein , Neuroblastoma/pathology , Nucleic Acid Hybridization , Risk , Survival AnalysisABSTRACT
Rhabdoid tumours (RTs) are rare but highly aggressive tumours of childhood. Their rarity and their miscellaneous locations make the diagnosis particularly challenging for pathologists. Central nervous system and peripheral RTs have been associated with biallelic inactivation of the hSNF5/INI1/SMARCB1 (hSNF5/INI1) tumour suppressor gene. Immunohistochemistry (IHC) with a monoclonal anti-hSNF5/INI1 antibody has recently been proposed as an efficient diagnostic tool for RTs. We have conducted a retrospective study of 55 tumours referred to our institution with a suspicion of RT. This analysis included pathological review, IHC with anti-hSNF5/INI1 antibody, and molecular investigation using quantitative DNA fluorescent analysis and sequencing of the nine exons of hSNF5/INI1. The molecular lesion could be detected in 37 of the 39 cases exhibiting negative staining for hSNF5/INI1. In the two discrepant cases, the lack of detection of genetic abnormality was probably owing to the presence of a high number of non-tumour cells in the samples. This indicates that hSNF5/INI1 IHC is very sensitive and highly specific for the detection of hSNF5/INI1 loss-of-function. Among the 38 cases with typical RT histological features, six failed to exhibit hSNF5/INI1 mutation and stained positive for hSNF5/INI1. This strongly supports the evidence of a second genetic locus, distinct from hSNF5/INI1, associated with RT. Conversely, seven tumours with histological features poorly compatible with RT stained negative for hSNF5/INI1; they nevertheless exhibited an age of onset and a clinical behaviour similar to RT. This suggests that hSNF5/INI1 inactivation is not strictly limited to typical RT but characterizes a wider family of hSNF5/INI1-deficient tumours. Consequently, we believe that anti-hSNF5/INI1 IHC should be performed widely, even when the pathological characteristics are not typical. The molecular investigation should be performed in infants when a rhabdoid predisposition syndrome is suspected.
Subject(s)
Biomarkers, Tumor/analysis , Chromosomal Proteins, Non-Histone/analysis , DNA-Binding Proteins/analysis , Kidney Neoplasms/diagnosis , Rhabdoid Tumor/diagnosis , Transcription Factors/analysis , Adult , Carcinoma/diagnosis , Carcinoma/genetics , Child, Preschool , Choroid Plexus Neoplasms/diagnosis , Choroid Plexus Neoplasms/genetics , Chromosomal Proteins, Non-Histone/genetics , DNA Mutational Analysis , DNA-Binding Proteins/genetics , Female , Gene Deletion , Genetic Markers , Humans , Immunohistochemistry/methods , In Situ Hybridization, Fluorescence , Infant , Keratins/analysis , Kidney Neoplasms/genetics , Male , Point Mutation , Retrospective Studies , Rhabdoid Tumor/genetics , SMARCB1 Protein , Transcription Factors/genetics , Vimentin/analysisABSTRACT
To retrospectively evaluate the incidence of tumour cell contamination of peripheral blood stem cell (PBSC) collections and to correlate these data with the clinical outcome after high-dose chemotherapy (HDCT) with stem cell rescue in patients with a high-risk Ewing tumour. Peripheral blood stem cell collections obtained from 171 patients were analysed. Tumour contamination was assessed by reverse transcriptase-polymerase chain reaction (RT-PCR). The files of 88 patients who underwent HDCT followed by PBSC reinfusion were reviewed in detail, and their outcome compared to the PBSC RT-PCR results. Seven of 88 PBSC collections (8%) contained tumour cells as detected by RT-PCR. Peripheral blood stem cells were collected after a median of five cycles of chemotherapy. No clinical factor predictive of tumour cell contamination of PBSC harvest could be identified. Event-free survival (EFS) and overall survival (OS) of the whole study population were 45.3 % and 51.8 % at 3 years from the date of the graft, respectively. Forty-five patients relapsed with a median time of 15 months after graft, only four of whom had tumour cell contamination of the PBSC harvest. Tumour cell contamination of PBSC collection is rare and does not seem to be associated with a significantly poorer EFS or OS in this high-risk population.
Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Hematopoietic Stem Cell Mobilization/methods , Hematopoietic Stem Cell Transplantation/methods , Oncogene Proteins, Fusion/genetics , Reverse Transcriptase Polymerase Chain Reaction/standards , Sarcoma, Ewing/pathology , Transcription Factors/genetics , Adolescent , Adult , Antigens, CD34/analysis , Bone Marrow Neoplasms/genetics , Bone Marrow Neoplasms/secondary , Child , Child, Preschool , Disease-Free Survival , Female , Granulocyte Colony-Stimulating Factor/therapeutic use , Humans , Infant , Leukapheresis , Male , Oncogene Proteins, Fusion/metabolism , Proto-Oncogene Protein c-fli-1 , RNA, Messenger/analysis , RNA-Binding Protein EWS , Retrospective Studies , Reverse Transcriptase Polymerase Chain Reaction/methods , Sarcoma, Ewing/genetics , Sensitivity and Specificity , Survival Rate , Transcription Factors/metabolism , Treatment OutcomeABSTRACT
Short stature and gonad failure can be a side effect of total body irradiation (TBI). The purpose of the study was to evaluate the factors influencing final height and gonad function after TBI. Fifty young adults given TBI during childhood were included. Twenty-seven had been treated with growth hormone (GH). Those given single 10 Grays (Gy) or fractionated 12 Gy TBI had similar characteristics, GH peaks, final heights and gonad function. After the end of GH treatment, 11/20 patients evaluated had GH peak >10 microg/l. Final height was <-2s.d. in 29 (58%). The height loss between TBI and final height (2.4+/-1.1 s.d.) was greater in those who were younger when irradiated (P<0.0001). When the GH-treated and -untreated patients were analyzed separately, this loss was correlated with the age at TBI at 4-8 years for the GH-treated and at 6-8 years for the untreated. Boys showed negative correlations between testicular volume and plasma follicle-stimulating hormone (FSH, P=0.0008) and between plasma FSH and inhibin B (P=0.005) concentrations. We concluded that the indications for GH treatment should be mainly based on the age at irradiation, taking into account the GH peak. The plasma FSH and inhibin B concentrations may predict sperm function.
Subject(s)
Body Height/radiation effects , Growth Disorders/blood , Testis/growth & development , Transplantation Conditioning/adverse effects , Whole-Body Irradiation/adverse effects , Adolescent , Age Factors , Child , Child, Preschool , Female , Follicle Stimulating Hormone/blood , Follow-Up Studies , Growth Disorders/drug therapy , Growth Disorders/etiology , Growth Disorders/pathology , Hematologic Neoplasms/complications , Hematologic Neoplasms/pathology , Hematologic Neoplasms/therapy , Hematopoietic Stem Cell Transplantation/adverse effects , Human Growth Hormone/administration & dosage , Human Growth Hormone/blood , Humans , Inhibins/blood , Male , Organ Size/radiation effects , Ovary/growth & development , Ovary/pathology , Ovary/radiation effects , Radiotherapy Dosage , Sex Factors , Spermatozoa/metabolism , Spermatozoa/pathology , Testis/pathology , Testis/radiation effectsABSTRACT
INTRODUCTION: Because of long-term complications of external beam radiation in retinoblastoma, a new therapeutic modality using chemotherapy and local treatments is used whenever possible. We conducted a retrospective study to evaluate visual results. PATIENTS AND METHOD: We studied visual acuity and ocular side effects in children presenting uni- or bilateral retinoblastoma in whom we were able to achieve conservative management without external beam treatment. The treatments that were used included chemotherapy, chemothermotherapy, diode laser, iodine 125 plaque brachytherapy, and cryotherapy. The initial characteristics (diameter, subretinal or vitreous seeding, and location) of each tumor, the treatments used, their results, and the visual function after age 4 years were recorded. RESULTS: We treated 429 children for retinoblastoma at the Curie Institute between October 1994 and December 2002. Two hundred twenty-seven eyes had conservative treatment without external beam. We were able to study the visual function in 102 eyes at a median age of 67 months. The median follow-up after the end of the treatment was 5 years. The mean visual acuity was 20/37 and 60% of the children had visual acuity of more than 20/40. Macular alteration was observed in 34 eyes. Statistical analysis showed that a larger tumor diameter of the retinal surface (p<0.0003) and location close to the macula (p<0.0001) were the most significant risk factors for vision loss. CONCLUSION: The visual results of the treatment of retinoblastoma by chemotherapy and local treatments is good when the tumors are not located close to the macula. Larger tumors also have a worse prognosis for vision.
Subject(s)
Retinal Neoplasms/therapy , Retinoblastoma/therapy , Visual Acuity , Child, Preschool , Combined Modality Therapy , Humans , Recovery of Function , Retinal Neoplasms/drug therapy , Retinoblastoma/drug therapy , Retrospective StudiesABSTRACT
This randomised trial was designed to compare two groups treated with different G-CSF administration schedules with a third group receiving no G-CSF, after autologous peripheral blood stem cell transplantation (APBSCT). Children and adults with haematological malignancies or solid tumours were randomly assigned to receive either 150 microg/m2/day of Lenograstim starting on day 1 (G1) or on day 5 (G5) post APBSCT, or no Lenograstim (G0). Randomisation was stratified according to the conditioning regimen (Busulfan vs TBI vs no Busulfan and no TBI) and the graft CD 34+ cell count. A total of 240 patients were randomised; 239 were evaluable. All three patient groups were comparable. Median duration of neutropenia was 9 days (4-40), and 10 days (5-15) in the G1 and G5 groups, respectively, significantly shorter than in the G0 group, 13 days (7-36) (P < 0.0001). No difference was observed in the duration of thrombocytopenia, transfusion support and extra-haematological complications. The duration of post transplant hospitalisation was significantly shorter in adults who received G-CSF. Clinical and cost arguments favour the initiation of G-CSF on day 5 in adults. The same policy could be applied in children given that clinical management is easier and costs are similar.