High precision conformal radiotherapy employing conservative margins in childhood benign and low-grade brain tumours.

BACKGROUND AND PURPOSE: To report local control and follow up outcome data of high precision conformal radiotherapy in childhood brain tumours. MATERIALS AND METHODS: Between December 1999 and December 2002, 26 children (17 boys and 9 girls, median age 11.5 years) with incompletely excised or recurrent benign and low-grade brain tumours [13 craniopharyngiomas, 11 low-grade gliomas (LGG) and 2 others] were treated with three-dimensional (3D) conformal radiotherapy (CRT) (12 patients) and stereotactic conformal radiotherapy (SCRT) (14 patients). Gross tumour volume (GTV) included neuro-imaging based visible tumour and/or resected tumour bed. Clinical target volume (CTV) consisted of GTV+ 5 mm margin and planning target volume (PTV) consisted of additional 5 mm margin for CRT and 2 mm for SCRT. Treatment was delivered with 3-9 conformal fixed fields to a median dose of 54 Gy/30 fractions. RESULTS: The actuarial 2 and 3 year disease free and overall survival was 96 and 100%, respectively (median follow up: 25 months, range 12-47 months). Radiological follow up available in 25 patients revealed complete response in 1, partial regression in 10, stable disease in 13 and progression in 1 patient (within the CTV). One patient with craniopharyngioma on a routine imaging revealed a mild asymptomatic cyst enlargement, which resolved with conservative management. A patient with chiasmatic glioma developed cystic degeneration and hydrocephalus 9 months after SCRT requiring cyst drainage and placement of a ventriculoperitoneal shunt. CONCLUSION: High-precision conformal techniques delivering irradiation to a computer generated target volume employing 7-10 mm 3D margins beyond the visible tumour and/or resected tumour bed appear to be safe in children with incompletely resected or recurrent benign and low-grade brain tumours, based on these data.     

CT cisternography in cerebrospinal fluid rhinorrhea: Could it have a therapeutic role?

Two cases of spontaneous cessation of cerebrospinal fluid (CSF) rhinorrhea following iohexol computerized tomographic (CT) cisternography are presented. This report contradicts the current thinking about conservative treatment in CSF rhinorrhea. We propose that iohexol CT cisternography may have a therapeutic role in the management of spontaneous CSF rhinorrhea.     

The Effect of Inert Atmospheric Packaging on Oxidative Degradation in Formulated Granules

No HeadingPurpose. Oxidative degradation of drug substances in pharmaceutical products is well documented and is thought to occur in many cases via autoxidative processes involving headspace molecular oxygen in the primary package. Reducing the headspace oxygen concentration inside a package could thus be an option for reducing oxidative degradation in pharmaceutical products. The purpose of this study is to examine the effect of headspace oxygen concentration and relative humidity (RH) on the oxidative degradation of a model pharmaceutical formulation.Methods. Model formulations, including a drug substance known to exhibit oxidative degradation, at two different drug/excipient ratios were packaged in stoppered glass vials maintained at different oxygen concentrations, (from 0% to 20.9%) and headspace relative humidities and were stored at 40°C. The oxidative degradation was quantified as a function of time.Results. The results clearly show dependence of oxidative degradation on headspace oxygen concen-tration, relative humidity, drug loading and time.Conclusions. The results provided insight into the effectiveness of inert atmospheric packaging (IAP) for protecting oxidation-labile products. In light of these observations, a few strategies for practically implementing inert atmosphere packaging are also presented.     

ADAMTS4 and its proteolytic fragments differentially affect melanoma growth and angiogenesis in mice

The metalloproteinase ADAMTS4 (ADAMTS, a disintegrin‐like and metalloproteinase with thrombospondin motif)/aggrecanase‐1 is highly expressed in cartilage and has been implicated in human arthritis. Although abundantly expressed in many types of cancer, its role in cancer remains unknown. In this work, we demonstrate for the first time that full‐length ADAMTS4 and its catalytically more active N‐terminal 53 kDa autocatalytic fragment both promote B16 melanoma growth and angiogenesis in mice. In contrast, overexpression of its catalytically inactive E362A mutant or truncated fragments containing only the C‐terminal ancillary domains suppresses melanoma growth and angiogenesis under similar conditions. Structure–function mapping revealed that the single thrombospondin‐type 1 repeat domain is essential and sufficient for the antitumorigenic activity displayed by the catalytically inactive ADAMTS4 isoforms. Suppression of tumor growth and angiogenesis in mice is accompanied by a significant increase in tumor cell apoptosis, whereas tumor cell proliferation is not affected. Importantly, we identified and demonstrated the presence of novel proteolytic fragments of ADAMTS4 containing essentially only the C‐terminal ancillary domains in cultured cells, and also in human cancer tissues, coexisting with full‐length and catalytically active N‐terminal fragments. The contrasting functions toward tumor growth in mice by the wild‐type proteinase and its catalytically inactive mutant correlate with their contrasting influences on angiogenesis signaling pathway molecules in B16 melanoma in mice. Our results suggest a complex role for ADAMTS4 in cancer with the functional balance of protumorigenic and antitumorigenic isoforms likely to act as an important parameter in determining the net influence of this metalloproteinase on tumor growth in vivo.     

Primary vaginal cancer treated with concurrent chemoradiation using Cis-platinum

PURPOSE: To evaluate the feasibility of concurrent weekly Cis-platinum chemoradiation (CRT) in the curative treatment of primary vaginal cancer. METHODS: A retrospective review was performed of all primary vaginal cancer patients treated with curative intent at the Ottawa Hospital Regional Cancer Centre between 1999 and 2004 using concurrent Cis-platinum CRT. RESULTS: Twelve patients were treated with concurrent weekly CRT. The median age at diagnosis was 56 years (range, 34-69 years), and the median follow-up was 50 months (range, 11-75 months). Ten patients (83%) were diagnosed with squamous cell carcinoma and 2 patients (17%) with adenocarcinoma. The distribution according to stage was as follows: 6 (50%) Stage II, 4 (33%) Stage III, and 2 (17%) Stage IVA. All patients received pelvic external beam radiotherapy (EBRT) concurrently with weekly intravenous Cis-platinum chemotherapy (40 mg/m(2)) followed by brachytherapy (BT). The median dose of EBRT was 4500 cGy given in 25 fractions over 5 weeks. Ten patients received interstitial BT, and 2 patients received intracavitary BT, with the median dose being 3000 cGy. The 5-year overall survival, progression-free survival, and locoregional progression-free survival rates were 66%, 75%, and 92%, respectively. Late toxicity requiring surgery occurred in 2 patients (17%). CONCLUSIONS: For the treatment of primary vaginal cancer, it is feasible to deliver concurrent weekly Cis-platinum chemotherapy with high-dose radiation, leading to excellent local control and an acceptable toxicity profile.     

Chronic inflammatory demyelinating polyneuropathy: A unique case of chronic disease with atypical features

We present a unique case of diffusely extensive Chronic Inflammatory Demyelinating Polyneuropathy (CIDP). Typically affecting the peripheral nervous system and manifesting with muscle weakness, breakdown or paresthesia, we present a case that additionally demonstrates; cranial nerve involvement, central nervous system parenchymal lesions, and chronic osseous remodeling of the nerve tracts. Cranial nerve involvement to this extent has only been described in one other case report to our knowledge. Central nervous system parenchymal lesions are extremely rare in CIDP and no discrete discussion about osseous remodeling has been presented, thus far, in the literature. The findings illustrated in this case may spur further understanding of imaging characteristics most associated with chronic CIDP disease and care measures that could help stratify patients most at risk for severe symptomologies.     

Treatment of Bone Tumors

In this article, the authors summarize the state of the art and future potential in the management of Osteosarcoma, Ewing's sarcoma, and Chondrosarcoma. They cover systemic therapy, surgical therapy, and radiotherapy, along with targeted therapies to inhibit signal transduction pathways. They discuss staging and the role of imaging evaluation to provide an overview of bone tumor treatment. Images presenting pathologic-radiologic correlations are included.     

A Web-Based Survey of Oculoplastic Surgeons Regarding the Management of Lower Lid Retraction

Purpose: To survey the opinion of oculoplastic surgeons on the assessment and management of lower eyelid retraction (LLR).

Methods: A web-based survey queried oculoplastic surgeon members of Ojoplast, Spanish and Brazilian Oculoplastic Societies on the management of LLR. The frequency and percentage proportions of the responses were analyzed.

Results: One hundred ninety-six oculoplastic surgeons participated in the survey. The main cause of LLR is post-blepharoplasty (62;31.6%). The most used sign to detect LLR is scleral show. The most common approaches to managing LLR are lateral canthal surgery (164/593;27.6%), autogenous spacers (148/593; 24.9%) and retractor release (131/593;22.1%). The preferred autogenous graft material includes ear cartilage (102/260;39.2%). The majority of surgeons (161/314; 51.3%) recommend massage or steroids injection (80/314;25.5%) for early post-blepharoplasty LLR, while, 54.1% (106/196) of participants suggested waiting for at least six months prior to surgical intervention. Frost suture is used after most LLR surgeries (154/196;91.1%). Incomplete correction is the main complication (111/310;35.8%) of LLR surgery. For mild LLR, 48% of the responders prefer clinical treatment; conversely, severe cases routinely require combined surgical techniques.

Conclusions: Oculoplastic surgeons frequently diagnose LLR based on scleral show. LLR management depends on the cause and severity of lid retraction. Mild cases, in general, receive clinical treatment and severe cases need a combination of surgical techniques and grafts.     

Intravenous streptokinase in the management of a subset of patients with unstable angina: a randomized controlled trial

We report the results of a randomized controlled trial of intravenous streptokinase in a subset of patients with unstable angina. Seventy-six patients were admitted with prolonged (more than 20 minutes) angina at rest of less than 3 weeks onset. Fifty-two patients continued to have more than 3 episodes of prolonged angina in 48 hours on medical therapy with metoprolol, isosorbide dinitrate, nifedipine and intravenous nitroglycerin. Forty-eight patients consented to enter the study and were randomized into two groups. The first group, of 24 patients, received 1.5 million units of streptokinase infusion and the second group, also of 24 patients, received a placebo. Pain relief within 48 hours was achieved in 19/24 (79.1%) patients after streptokinase infusion as compared to 9/24 (37.5%) of the controls (P less than 0.05). Approximately 90% (17/19) of patients responding to streptokinase therapy were relieved of chest pain within the first six hours as against none in the controls. The incidence of acute myocardial infarction within six months was 12.5% (3/24) in those receiving streptokinase and 25% (6/24) in the controls. Mortality at six months stood at 8.33% (2/24) in the treated patients and 16.6% (4/24) in the controls. Intravenous streptokinase thus appears to be of benefit in patients with angina at rest of recent onset which does not respond to conventional medical therapy.