Prognostic relevance of clinical and molecular risk factors in children with high-risk medulloblastoma treated in the phase II trial PNET HR+5

BackgroundHigh-risk medulloblastoma is defined by the presence of metastatic disease and/or incomplete resection and/or unfavorable histopathology and/or tumors with MYC amplification. We aimed to assess the 3-year progression-free survival (PFS) and define the molecular characteristics associated with PFS in patients aged 5–19 years with newly diagnosed high-risk medulloblastoma treated according to the phase II trial PNET HR+5.MethodsAll children received postoperative induction chemotherapy (etoposide and carboplatin), followed by 2 high-dose thiotepa courses (600 mg/m²) with hematological stem cell support. At the latest 45 days after the last stem cell rescue, patients received risk-adapted craniospinal radiation therapy. Maintenance treatment with temozolomide was planned to start between 1–3 months after the end of radiotherapy. The primary endpoint was PFS. Outcome and safety analyses were per protocol (all patients who received at least one dose of induction chemotherapy).ResultsFifty-one patients (median age, 8 y; range, 5–19) were enrolled. The median follow-up was 7.1 years (range: 3.4–9.0). The 3 and 5-year PFS with their 95% confidence intervals (95% CI) were 78% (65–88) and 76% (63–86), and the 3 and 5-year OS were 84% (72–92) and 76% (63–86), respectively. Medulloblastoma subtype was a statistically significant prognostic factor (P-value = 0.039) with large-cell/anaplastic being of worse prognosis, as well as a molecular subgroup (P-value = 0.012) with sonic hedgehog (SHH) and group 3 being of worse prognosis than wingless (WNT) and group 4. Therapy was well tolerated.ConclusionsThis treatment based on high-dose chemotherapy and conventional radiotherapy resulted in a high survival rate in children with newly diagnosed high-risk medulloblastoma.     

Restoration of thoracic kyphosis by simultaneous translation on two rods for adolescent idiopathic scoliosis

Introduction

Sagittal and axial corrections of the three-dimensional deformity characteristic of scoliosis remain challenging.

Materials and Method

The author developed a new technique for scoliosis correction consisting of the translation of vertebrae simultaneously towards two rods, which are pre-bent to the correct sagittal profile. Using two rods ensures both reduction and stabilization of the curve. The system includes stable anchorages with polyaxial-threaded extensions that connect to the rods. Deformity reduction is done by tightening nuts simultaneously and progressively on the two rods. Results demonstrate the efficiency of this technique to achieve normal thoracic kyphosis (>20°) in all 99 patients, with a mean gain of 19° of thoracic kyphosis in hypokyphotic cases. Coronal correction was 70−80 % with a vertebral rotation gain of 40 % where derotation connectors were used.

Conclusions

In a large consecutive series of patients, this new technique allows to achieve a good 3D correction of the scoliosis.

     

PET imaging of fatty acid amide hydrolase in the brain: synthesis and biological evaluation of an 11C-labelled URB597 analogue

IntroductionFatty acid amide hydrolase (FAAH) is part of the endocannabinoid system (ECS) and has been linked to the aetiology of several neurological and neuropsychiatric disorders. So far no useful PET or SPECT tracer for in vivo visualisation of FAAH has been reported. We synthesized and evaluated a carbon-11-labeled URB597 analogue, biphenyl-3-yl [¹¹C]-4-methoxyphenylcarbamate or [¹¹C]-1, as potential FAAH imaging agent.MethodsThe inhibitory activity of 1 was determined in vitro using recombinant FAAH. Radiosynthesis of [¹¹C]-1 was performed by methylation using [¹¹C]-CH₃I, followed by HPLC purification. Biological evaluation was done by biodistribution studies in wild-type and FAAH knock-out mice, and by ex vivo and in vivo metabolite analysis. The influence of URB597 pretreatment on the metabolisation profile was assessed.Results[¹¹C]-1 was obtained in good yields and high radiochemical purity. Biodistribution studies revealed high brain uptake in wild-type and FAAH knock-out mice, but no retention of radioactivity could be demonstrated. Metabolite analysis and URB597 pretreatment confirmed the non-FAAH-mediated metabolisation of [¹¹C]-1. The inhibition mechanism was determined to be reversible. In addition, the inhibition of URB597 appeared slowly reversible.ConclusionsAlthough [¹¹C]-1 inhibits FAAH in vitro and displays high brain uptake, the inhibition mechanism seems to deviate from the proposed carbamylation mechanism. Consequently, it does not covalently bind to FAAH and will not be useful for mapping the enzyme in vivo. However, it represents a potential starting point for the development of in vivo FAAH imaging tools.     

Combined treatment of cancer of the posterior oral cavity and oropharynx

Ninety composite resections were carried out as primary treatment for a squamous carcinoma of the tonsillar region between 1970 and 1978. All patients have been followed-up for at least 3 years, except for 5 who have been lost to follow-up. All patients received postoperative radiotherapy (between 50 Gy and 65 Gy depending on the tumour resection status). Sixty-one patients received preoperative chemotherapy and 42% had clinical reduction of tumour size. The overall survival was 45.5% at 3 years and 43% at 5 years. Local recurrences were the most frequent oncological failure (25%). Tumours classed T3, insufficient tumour resection and lymph node invasion had poor prognostic value. We emphasize the necessity for primary surgery with preoperative chemotherapy and postoperative radiotherapy for squamous carcinoma of the posterior oral cavity and oropharynx.     

The isolated pulmonary nodule. Biopsy guided by x-ray computed tomography

Transparietal CT-guided biopsy location can be successfully performed for isolate pulmonary nodules, defined as lesions with a maximal diameter of 3 cm, without any other parenchymal or mediastinal abnormality. A 21 G needle has been used according to an identical protocole in 64 cases (10 benign, 54 malignant). The biopsy was successful in 77.7% of the malignant cases. In relation to the diameter of the nodules, biopsy was successful in 66.7% of the nodules smaller than 2 cm and in 76% of the nodules ranging from 2 to 3 cm. The complications observed were rare (1 case of pneumothorax requiring drainage, 9 cases of pneumothorax without clinical signs and simply followed up, 4 cases of minor hemoptysis requiring no treatment and 5 cases of hematomas smaller than 5 cm on CT).     

MR features of isolated uterine relapse in an adolescent with acute lymphoblastic leukaemia

Relapses of lymphoblastic leukaemia traditionally involve the central nervous system and testes in boys. Involvement of the female pelvic organs is frequently found at autopsy; however, involvement of the cervical uterus is rare and even less commonly symptomatic. A 13-cm uterine mass was discovered in a 15-year-old adolescent with a history of lymphoblastic leukaemia during childhood. Pelvic MRI was the best tool to assess the size, characteristics and invasive nature of this lesion of the uterine cervix. To our knowledge, this is a unique case in that we describe the MRI appearance of a relapsing lymphoblastic leukaemic mass both before and after treatment.     

MRI for the diagnosis of recurrent middle ear cholesteatoma in children—can we optimize the technique? Preliminary study

Background

Recurrent cholesteatoma after surgical excision occurs frequently in children. Until recently, a surgical second look was mandatory and considered as standard reference. MRI including a delayed T1 sequence after gadolinium injection and diffusion-weighted imaging (DWI) has proved its efficiency but has been evaluated mainly in adults.

Objective

Our purpose was to evaluate the accuracy of DWI to diagnose recurrence of cholesteatoma in children.

Materials and methods

We evaluated prospectively with MRI 20 ears in 18 children who had had surgery for cholesteatoma. We compared DWI and delayed T1-weighted images following gadolinium administration with intraoperative or follow-up findings. We calculated the sensitivity and specificity of each sequence for the diagnosis of recurrent cholesteatoma.

Results

Sensitivity to diagnose recurrent cholesteatoma was 87% for both DWI and delayed post-gadolinium sequences, specificity was 71% and 83%, respectively. Adding both sequences, the sensitivity was 87%, the specificity 100%. There was one false negative probably due to small size recurrence.

Conclusion

In our series, DWI was reliable to diagnose recurrent cholesteatoma in children and allows avoiding surgery when negative. However, because small recurrences less than 5 mm may be missed, follow-up must be prolonged (5 years).     

Relations Between Respiratory Changes in R-Wave Amplitude and Arterial Pulse Pressure in Mechanically Ventilated Patients

Introduction  

R-wave obtained from the electrocardiogram depends on ventricular stroke volume. We assessed the relationship between respiratory variations in R-wave (ΔRDII) and in pulse pressure (ΔPP) during general anesthesia.     

Comparison of Multiplane Transesophageal Echocardiography and Contrast-enhanced Helical CT in the Diagnosis of Blunt Traumatic Cardiovascular Injuries

Background: Multiplane transesophageal echocardiography (TEE) and helical computed tomography (CT) of the chest have been validated separately against aortography for the diagnosis of acute traumatic aortic injuries (ATAI). However, their respective diagnostic accuracy in identifying blunt traumatic cardiovascular lesions has not been compared.

Methods: During a 3-yr period, 110 consecutive patients with severe blunt chest trauma (age: 41 +/- 17 yr; injury severity score: 34 +/- 14) prospectively underwent TEE and chest CT as part of their initial evaluation. Results of both imaging methods were interpreted independently by experienced investigators and subsequently compared. All cases of subadventitial acute traumatic aortic injury were surgically confirmed.

Results: Seventeen patients had vascular injury and 11 had cardiac lesions. TEE and CT identified all subadventitial disruptions involving the aortic isthmus (n = 10) or the ascending aorta (n = 1) that necessitated surgical repair. In contrast, CT only depicted one disruption of the innominate artery. TEE detected injuries involving the intimal or medial layer, or both, of the aortic isthmus in four patients with apparently normal CT results who underwent successful conservative treatment. All cardiac injuries but two were identified only by TEE.