Diffusion-weighted imaging in differentiating mid-course responders to chemotherapy for long-bone osteosarcoma compared to the histologic response: an update.

BACKGROUND: Diffusion-weighted imaging (DWI) has been described to correlate with tumoural necrosis in response to preoperative chemotherapy for osteosarcoma. OBJECTIVE: To assess the accuracy of DWI in evaluating the response to neoadjuvant chemotherapy at the mid-course treatment of long-bone osteosarcoma and in predicting survival. MATERIALS AND METHODS: We conducted a prospective single-centre study over a continuous period of 11 years. Consecutive patients younger than 20 years treated with a neoadjuvant regimen for peripheral conventional osteosarcoma were eligible for inclusion. Magnetic resonance imaging (MRI) with DWI was performed at diagnosis, and mid- and end-course chemotherapy with mean apparent diffusion coefficients (ADC) calculated at each time point. A percentage less than or equal to 10% of the viable residual tissue at the histological analysis of the surgical specimen was defined as a good responder to chemotherapy. Survival comparisons were calculated using the Kaplan-Meier method. Uni- and multivariate analyses with ADC change were performed by Cox modelling. This is an expansion and update of our previous work. RESULTS: Twenty-six patients between the ages of 4.8 and 19.6 years were included, of whom 14 were good responders. At mid-course chemotherapy, good responders had significantly higher mean ADC values (P=0.046) and a higher increase in ADC (P=0.015) than poor responders. The ADC change from diagnosis to mid-course MRI did not appear to be a prognosticator of survival and did not impact survival rates of both groups. CONCLUSION: DWI at mid-course preoperative chemotherapy for osteosarcoma should be considered to evaluate the degree of histological necrosis and to predict survival. The anticipation of a response to neoadjuvant treatment by DWI may have potential implications on preoperative management.

MRI evaluation of the hydration status of non-pathological lumbar intervertebral discs in a pediatric population.

INTRODUCTION: The intervertebral disc (IVD) is made up of the annulus fibrosus (AF) and the nucleus pulposus (NP) - an inert hydrated complex. The ability of the IVD to deform is correlated to that of the NP and depends on its hydration. As the IVD ages, its hydration decreases along with its ability to deform. In adolescent idiopathic scoliosis, one of the etiological hypotheses pertains to the IVD, thus making its condition relevant for the diagnosis and monitoring of this pathology. HYPOTHESIS: IVD hydration depends on sex, age and spine level in an asymptomatic pediatric population. The corollary is data on a control group of healthy subjects. MATERIAL AND METHODS: A cohort of 98 subjects with normal spine MRI was enrolled; their mean age was 13.3 years. The disc volume and hydration of each IVD was evaluated on T2-weighted MRI sequences, using previously validated image processing software. This evaluation focused on the lumbar spine, from the thoracolumbar junction to the lumbosacral junction. It was assumed that IVD hydration was related to the ratio of NP and AF volumes. A mixed multivariate linear analysis was used to explore the impact of age, sex and spinal level on disc hydration. RESULTS: Disc hydration was higher overall in boys than in girls, but this difference was not significant. Hydration increased with age by +0.005 for each additional year (p=0.0213). Disc hydration appears to be higher at the thoracolumbar junction than the lumbar spine, although this difference was not significant. CONCLUSION: Through this MRI study, we established a database of non-pathological lumbar disc hydration as a function of age, sex and spinal segment along with 95% confidence intervals. LEVEL OF EVIDENCE: IV.

Diffusion-weighted MRI for outcome prediction in early Legg-Calvé-Perthes disease: Medium-term radiographic correlations.

BACKGROUND: Outcome prediction at the early sclerotic stage of Legg-Calvé-Perthes disease (LCPD) is valuable to select patients likely to benefit from early surgery. The metaphyseal apparent diffusion coefficient (ADC) ratio correlated significantly with Herring's classification of LCPD in a preliminary study of 49 MRIs, in which values greater than 1.63 were associated with poor outcomes. The objective of this study was to determine whether the femoral neck ADC ratio, with the 1.63 cut-off, determined at the initial stage of LCPD correlated with medium-term radiographic outcomes. HYPOTHESIS: The metaphyseal ADC ratio correlates significantly with medium-term radiographic outcomes of LCPD. MATERIALS AND METHODS: A prospective study was performed in 27 children (mean age, 13 years; range, 9.5-16 years) who underwent 49 MRIs at the sclerosis or fragmentation stage of unilateral LCPD. ADCs measured bilaterally at the femoral head and neck were used to compute the corresponding ADC ratios between the affected and unaffected sides. The patients received regular follow-up for at least 5 years. The correlation between the ADC ratios and Stulberg grade at last follow-up was assessed. RESULTS: After a mean follow-up of 6.8 years (range, 5.2-8.4 years) from the date of the first MRI, 13 hips were Stulberg 1 or 2, 13 were Stulberg 3 or 4, and 1 was Stulberg 5. The metaphyseal ADC ratio increased significantly with the Stulberg grade (p<0.01). When only MRIs obtained at the early stage of sclerosis were considered, the correlation remained significant (p=0.03). It was also significant in the subgroup of surgically treated patients (p<0.0001) but was not significant in the subgroup without surgery (p=0.51). A metaphyseal ADC ratio greater than 1.63 was associated with a worse Stulberg grade (p=0.02). DISCUSSION/CONCLUSION: Diffusion-weighted MRI is a non-irradiating and non-invasive investigation that contributes to the management of LCPD when used in combination with morphological MRI sequences. Elevation of the femoral neck ADC is a finding of adverse prognostic significance that correlates with Herring's grade at the fragmentation stage and with Stulberg's grade at the healed stage. Early ADC elevation in the affected femoral neck can serve to select those patients most likely to benefit from early surgery before the fragmentation stage, i.e., before Herring's classification can be applied. LEVEL OF EVIDENCE: III, prospective uncontrolled study 3.

Prenatal diagnosis of right-sided diaphragmatic hernia and ipsilateral intrathoracic kidney in a female fetus: a rare observation.

Congenital diaphragmatic hernia is a rare congenital malformation, as well as kidney ectopia. Among kidney ectopias, the intrathoracic one is the rarest. Those malformations concern more frequently boys, and affected more the left than the right side. Their association is poorly reported in the literature. We report the rare case of an early sonographic prenatal diagnosis of intrathoracic kidney at 22 weeks of gestation in a female fetus, completed on the follow-up by the diagnosis of an associated diaphragmatic hernia at 33 weeks of gestation. If chest mass is diagnosed prenatally or in neonate, ITK should be considered in a differential diagnosis, all the more if the ipsilateral renal fossa is empty. An associated DH should be searched if ITK is confirmed. Isolated ITK usually requires no specific treatment, in contrast with ITK associated with DH.

Non-contrast-enhanced MR angiography using time-spin labelling inversion pulse technique for detecting crossing renal vessels in children with symptomatic ureteropelvic junction obstruction: comparison with surgical findings.

OBJECTIVES: Investigate the feasibility and evaluate the accuracy of non-contrast-enhanced MR angiography (NC-MRA) using time-spin labelling inversion pulse (time-SLIP)to identify crossing renal vessels (CRVs) in children requiring surgical treatment of ureteropelvic junction (UPJ) obstructionand compare to laparoscopic findings. MATERIALS AND METHODS: Nineteen children ranging from 6 to 16 years of age underwent NC-MRA using the time-SLIP technique before surgery. Two independent readers analysed the MRA images. Number of renal arteries and presence or absence of CRVs were identified and compared with surgicalfindings. Image quality was assessed, as well as the presence of CRVs and measurement of renal pelvis diameter. Intra and inter-reader agreement was calculated using Cohen's kappa coefficient and Bland-Altman plots. RESULTS: The overall image quality was fair or good in 88% of cases. NC-MRA demonstrated CRVs at the level of the obstruction in 10 children and no CRV in 9 children. All were confirmed intra-operatively except in one of the nine children. Sensitivity, specificity, NPV, PPV for predicting CRVs were 92%, 100%, 100% and 87.5%, respectively, for both readers. CONCLUSION: NC-MRA is a good alternative to contrast-enhanced MRA and CT scanning for identifying CRVs in children with symptomatic UPJ. KEY POINTS: • Time-SLIP technique offers acceptable imaging quality for identifying crossing renal vessel. • Time-SLIP technique is easy to apply to the renal MRA examination. • Time-SLIP technique is an alternative to contrast-enhanced MRA and CT scanning.

Low-dose biplanar radiography can be used in children and adolescents to accurately assess femoral and tibial torsion and greatly reduce irradiation.

PURPOSE: To evaluate in children the agreement between femoral and tibial torsion measurements obtained with low-dose biplanar radiography (LDBR) and CT, and to study dose reduction ratio between these two techniques both in vitro and in vivo. MATERIALS AND METHODS: Thirty children with lower limb torsion abnormalities were included in a prospective study. Biplanar radiographs and CTs were performed for measurements of lower limb torsion on each patient. Values were compared using Bland-Altman plots. Interreader and intrareader agreements were evaluated by intraclass correlation coefficients. Comparative dosimetric study was performed using an ionization chamber in a tissue-equivalent phantom, and with thermoluminescent dosimeters in 5 patients. RESULTS: Average differences between CT and LDBR measurements were -0.1° ±1.1 for femoral torsion and -0.7° ±1.4 for tibial torsion. Interreader agreement for LDBR measurements was very good for both femoral torsion (FT) (0.81) and tibial torsion (TT) (0.87). Intrareader agreement was excellent for FT (0.97) and TT (0.89). The ratio between CT scan dose and LDBR dose was 22 in vitro (absorbed dose) and 32 in vivo (skin dose). CONCLUSION: Lower limb torsion measurements obtained with LDBR are comparable to CT measurements in children and adolescents, with a considerably reduced radiation dose. KEY POINTS: • LDBR and CT lower-limb torsion measurements are comparable in children and adolescents. • LDBR considerably reduced radiation dose necessary for lower-limb torsion measurements. • LDBR can be used for evaluation of lower limb-torsion in orthopaediatric patients.

Phase II study of cisplatin and oral VP16 in patients with refractory or relapsed Ewing sarcoma.

BACKGROUND: Phase II trials demonstrate the activity of cisplatin in patients with refractory Ewing sarcoma family tumours (ESFT) and also the feasibility of giving cisplatin with oral VP16 in a variety of different cancers. This trial was conducted to evaluate the activity and toxicity profile of this combination delivered as outpatient therapy in patients with refractory/relapsed ESFT. METHODS: Cisplatin was administered on days 1, 8 and 15 and days 29, 36 and 43 (70 mg/m(2)/dose for patients <21 years of age and 50 mg/m(2)/dose ≥21 years). VP16 was administered at a dose of 50 mg/m(2) on days 1-15 and days 29-43 inclusive. A three-stage Fleming statistical design was used for analysis. RESULTS: Between January 2003 and October 2006, 45 patients aged between 5 and 46 years (median 19) were enrolled. Thirty-eight were evaluable for response. Patients had previously received one to three lines of chemotherapy (median = one). Seventy-three per cent of the patients had grade 3/4 neutropenia, 20 % developed fever, 40 % had grade 3/4 anaemia, 68 % grade 3/4 thrombocytopenia and 16 % grade 2/3 ototoxicity. Measured response after 2 cycles: 0 CR, 7 PR (18 %), 13 SD (34 %), 18 PD (48 %). There was excellent concordance between unidimensional and bidimensional criteria in 31 of 33 responses (94 %). PFS at 1 year was 39 %, with a median PFS of 6 months. Overall survival at 1 year was 44 %; median survival was 11 months. CONCLUSIONS: Cisplatin combined with oral VP16 is well tolerated and has acceptable side effects, but limited clinical activity in refractory/relapsed ESFT.

Mechanical occlusion of the inferior vena cava: an early complication after repair of pectus excavatum using the Nuss procedure.

The Nuss procedure is the most widely used surgical procedure to correct pectus excavatum. Although it is a minimally invasive approach, a number of major early complications, such as heart perforation, have been reported. We describe a 15-year-old boy in whom acute occlusion of the inferior vena cava developed after a Nuss repair. The diagnosis was confirmed by emergency postoperative CT examination, and treatment consisted of immediate removal of the Nuss bar.

Pulmonary and intestinal congenital anomalies masquerading as cystic suprarenal masses.

OBJECTIVES: The prenatal finding of a cystic suprarenal mass (CSM) presents a wide differential diagnosis. The aim of this study was to present the natural course and outcome of antenatally diagnosed CSMs. METHODS: We reviewed the medical records of patients with prenatally detected CSMs that were assessed between January 1998 and December 2011. Retrospective data collection included the age at the time of diagnosis, the size of the mass, and the sonographic evolution of the mass. Surgical treatment was indicated in cases of malignant tumors and symptoms or when size increased. RESULTS: The observation period ranged from 1 month to 10 years. The data of 21 patients were analyzed. The median length of follow-up was 32 months (ranging from 2 to 131 months). A total of 13 masses were detected on the left side and 8 on the right side. In 13 patients, the lesions disappeared after a median of 7 months (ranging from 0 to 37 months). Surgery was performed in two neonates: one for a teratoma at 10 days postpartum, and one for a neuroblastoma at 17 days postpartum. Six patients had an extralobar pulmonary sequestration (ELPS), and in four patients, surgical resection was performed at an average of 9.2 months (ranging from 1 to 20 months) postpartum, because of an infection or increase in ELPS size. Histological examination confirmed the pulmonary sequestration. An association with congenital cystic adenomatoid malformation (CCAM) was found in one patient, and ectopic pancreatic tissue was discovered in another patient. Two patients conservatively managed remain under observation. CONCLUSIONS: During the neonatal period, the accurate assessment of CSMs is necessary to exclude the presence of malignant tumors. Most patients can be conservatively managed, with close follow-up, including radiological assessment. If the mass persists after 1 year of age, ELPS should be considered as a probable diagnosis, and minimally invasive laparoscopic surgery can be performed, as it provides both definitive diagnosis and treatment.

The surgical management and outcome of congenital mediastinal malformations.

We reviewed our institutional experience with congenital mediastinal masses and compared the postnatal management and outcome of patients with or without prenatal diagnosis. Between January 1997 and August 2011, 24 patients underwent surgical procedures for congenital mediastinal mass. For eight patients, the mass was detected by prenatal ultrasonography at 27 weeks of gestation (range 22-35). Postnatal management consisted in open surgery for seven patients at a mean age of 9 months (range 1 day-20 months) and sclerotherapy for one lymphangioma at 5 months of life. Sixteen patients had postnatal diagnosis at 137 months (±194) of median age. Eight bronchogenic cysts, seven bronchopulmonary foregut malformations, five teratomas, three lymphangiomas and one haemangioma were operated on. The median age at resection was 28 months (1 day-15 years). There were four emergency procedures and no surgical mortality. The median follow-up was 45 months (3-144). The duration of mechanical ventilation and hospital stay was, respectively, 4.6 h and 7.5 days for antenatal patients and 24.3 h and 14.3 days for postnatal diagnosed patients. Prenatal diagnosis allows early management of congenital mediastinal malformations. Early resection can be performed prior to the occurrence of symptoms ∼1 year of life and is associated with an excellent outcome and less morbidity.

A rare cause of anaemia associated with hypertension in a 14-year-old girl.

We report a rare example of anaemia and hypertension due to an incomplete Carney triad in a 14-year-old girl with no previous medical history. This rare non-familial syndrome generally involves two disparate tumours: gastrointestinal stromal tumour, paraganglioma and/or pulmonary chondroma. The complete triad is a syndrome that involves at least five loci: stomach, oeophagus, lung, the paraganglionic system, adrenal (cortex or medulla). The pathogenesis is unclear as these tumours have different embryological origins. Surgical treatment is necessary, and long-term follow-up is advisable as patients with Carney triad may re-present with tumour(s), even several years after the first presentation.

Hypophosphatasia may lead to bone fragility: don't miss it.

Hypophosphatasia is an inheritable disorder characterised by defective bone mineralisation due to the impaired activity of tissue-non-specific alkaline phosphatase (AP). Clinical presentation ranges from stillbirth without mineralised bone to pathological fractures in late adulthood. During childhood, the main manifestations include rickets, growth delay and dental problems. Fractures and bone pain usually characterise the adult form. A 9-year-old girl was referred for repetitive fractures after minimal trauma. She had normal growth, normal sclerae, no rickets and minimal dental abnormalities. Her sister had also presented fractures. The proband, her sister and mother had low total and bone-specific AP levels and E435K mutation in exon 12 of the liver/bone/kidney AP gene. Low AP levels must lead to genetic analysis. Bone fragility and repetitive fractures may be symptoms of hypophosphatasia in childhood, which must not be neglected. Associated factors such as vitamin D or calcium deficiency must be prevented. In conclusion, hypophosphatasia must not be forgotten as an aetiological factor of repetitive fractures or bone pain in children and AP activity should be checked accurately.

Fetal ovarian cysts management and ovarian prognosis: a report of 82 cases.

BACKGROUND/PURPOSE: Fetal ovarian cysts are frequently complicated by intracystic hemorrhage without associated clinical signs, which is often secondary to ovarian torsion leading to loss of the ovary. The aim of this study was to evaluate ovarian outcome and the place of prenatal management and surgery in the first few days of life in order to save the ovary. METHODS: Between January 1987 and June 2006, 82 fetal ovarian cysts in 79 patients were managed and clinically and ultrasonographically followed up for several months (median, 11 months; range, 6 months to 10 years) in all of the cases where the ovary was not removed. The ultrasonographic results regarding the ovarian parenchyma were broken down into 3 categories: follicular ovary, homogeneous ovary, and undetected ovary. RESULTS: Twenty-seven cysts remained simple throughout their evolution, and 55 were complicated by intracystic hemorrhage usually several weeks before birth. Overall, after disappearance of the cyst, a follicular ovary was detected in only 39% of the cases (32/82) and more often when the cyst was simple than when it presented an intracystic hemorrhage (85% vs 16.4%, chi(2), P < .0001). CONCLUSIONS: A review of our series confirms the poor ovarian outcome linked to ultrasonographic signs of intracystic hemorrhage. Preventive action by puncture of "simple" cysts is still being studied. The presence of a bilateral cyst can, if pulmonary maturity has been reached, be an argument for inducement of premature birth with a view to performing conservative surgery. After birth, surgery in the first few days of life is only justified if the signs of intracystic hemorrhage appeared in the period very close to birth.

Rapid development of an osteosarcoma after surgical resection of an osteochondroma.

The rapid development of an osteosarcoma, after surgical resection of an osteochondroma, has not been yet reported. We present here the case of a 12-year-old girl that had, in less than 2 months, an osteosarcoma at the initial site of a treated osteochondroma. Comparative Genomic Hybridization analyses showed that the 2 tumors were genetically distinct, suggesting a distant, if any, relationship. The possible implication of a deregulated tissue homeostasis caused by the surgical intervention is discussed. Proangiogenic factors involved in the tissue healing could be the triggering factor favoring tumor angiogenesis and explaining the very rapid progression of the tumor.

Phase II study of temozolomide in relapsed or refractory high-risk neuroblastoma: a joint Société Française des Cancers de l'Enfant and United Kingdom Children Cancer Study Group-New Agents Group Study.

PURPOSE: To determine the response rate (RR) of neuroblastoma (NB) in children to temozolomide (TMZ), and evaluate the duration of response and tolerance of the drug in this patient population. PATIENTS AND METHODS: A multicenter, phase II evaluation of an oral, daily schedule of TMZ (200 mg/m2/d x 5 days every 28 days) was undertaken in children with refractory or relapsed high-risk NB (metastatic or localized with Myc-N amplification). Response assessment was based on imaging with two-dimentional measurement of disease and meta-iodobenzylguanidine (MIBG) score. Activity was defined by a reduction in lesion size or isotope uptake at anytime. Methodology included a two-step design using Fleming's method with a first step of 15 patients and a second of 10 additional patients if two to four responses had been observed in the first cohort. All data was centrally reviewed by a panel. RESULTS: Twenty-five assessable patients were recruited over a 14-month period in 14 centers and received 94 cycles of chemotherapy. Twenty-three patients had metastatic NB either refractory (n = 9) or in relapse (n = 14). Grade 3 or 4 thrombocytopenia was the most frequent toxicity (16% of cycles). Myelosuppression resulted in treatment delays and dose reductions (24% and 21% of cycles, respectively). Response (complete response, very good partial response, or partial response) was observed in five patients (RR = 20% +/- 8%) with a median duration of 6 months and an objective or mixed response in five additional patients. CONCLUSION: Temozolomide shows activity in heavily pretreated patients with NB, and deserves further evaluation in combination with another drug.

Wrist anomalies in Turner syndrome compared with Leri-Weill dyschondrosteosis: a new feature in Turner syndrome.

UNLABELLED: We analysed bone age radiographs in 102 girls with Turner syndrome and compared the findings with 93 control girls and nine girls with Leri-Weill syndrome. Various signs were analysed: radial bowing or Madelung deformity, maximal/minimal height of the radial epiphysis, brachymetacarpia of the 4th digit, carpal and epiphyseal angle, as well as a new sign the distal radio-ulnar physeal disparity. Two values differed significantly between the Turner group and the control group, the first being the epiphyseal angle which has already been reported to be greater in Turner syndrome, and the second being the new sign we have been able to describe. Turner patients had an increased distance between the ulnar and radial metaphysis, or "distal radio-ulnar physeal disparity", the ulnar being shorter. Furthermore, in 27% of cases the medial extremity of the ulnar epiphysis was flattened and passed below the distal extremity of the radius, whose medial part projected over the distal extremity of the ulna, thus reproducing in reverse the characteristic feature of Leri-Weill syndrome. In the growth hormone-treated Turner patients, we found a significant correlation between distal radio-ulnar physeal disparity and growth velocity expressed in cm/year (r = 0.28; P < 0.002) or in SDS/bone age (r = 0.21; P < 0.03) during the first year of treatment. CONCLUSION: the value of this new sign requires further investigation.

Assessment of the position of the navicular by three-dimensional magnetic resonance imaging in infant foot deformities.

As the navicular is unossified in infants with foot deformities, until 5 years old (boys) and 3 years old (girls), it is difficult to give the exact position of hindfoot bones. Magnetic resonance imaging associated with three-dimensional reconstruction allows the visualization of the cartilaginous volume of the bones and the measurement of the relationships of the navicular with the talus. In normal feet, we noted that in the coronal plane the navicular was laterally situated (75%) relative to the talus. In club feet (17 patients), the navicular and the cuboid had a large medial displacement (77%) with a slight pronation movement in the sagittal plane. In suspected skewfoot (seven feet) we noted three cases with a lateral subluxation of the navicular. This objective technique of measurement may be of value for diagnosis and treatment of foot deformities.