Canadian Cancer Trials Group (CCTG) IND215: A phase Ib study of Selumetinib in patients with untreated advanced or metastatic NSCLC who are receiving standard chemotherapy regimens.

Introduction Selumetinib (AZD6244, ARRY-142886) is a potent inhibitor of MEK1/2, thereby inhibiting phosphorylation of ERK2. We investigated the toxicity and the recommended phase II dose of the combination of selumetinib with two platinum based first line chemotherapy combinations in non-small cell lung cancer. Methods This was a phase I trial of escalating doses of selumetinib with carboplatin (AUC 6), paclitaxel (200 mg/m2) (cohort 1) or pemetrexed (500 mg/m2) and cisplatin (75 mg/m2) (cohort 2) in patients with chemotherapy naïve, advanced or metastatic NSCLC. Patients enrolled on cohort 2 had non-squamous histology. Dose escalation of selumetinib proceeded using a 3 + 3 design: 50 mg b.i.d. days 2-19 (dose level 1); 75 mg b.i.d. days 2-19 (dose level 2); and 75 mg b.i.d. continuously. Adverse events were evaluated using CTC AE v4 and response by RECIST 1.1. Results Thirty-nine patients were enrolled (cohort 1 n = 16; cohort 2, n = 23). There were no dose limiting toxicities in either cohort and the recommended phase II dose for both regimens was standard doses of carboplatin, paclitaxel or pemetrexed and cisplatin with continuous selumetinib at a dose of 75 mg b.i.d. Most adverse events were grade 1 or 2 and were predominantly diarrhea, nausea, stomatitis, peripheral edema, neutropenia, and skin rash. Response rate was 37.5% for cohort 1 and 30.4% for cohort 2. Conclusion Selumetinib at a dose of 75 mg b.i.d continuously can be safely combined with paclitaxel and carboplatin or pemetrexed and cisplatin in patients with advanced or metastatic NSCLC. This trial provided the dose for the regimens used in a randomized phase II trial in NSCLC (CCTG IND.219).

Return to sport following stress fractures of the great toe sesamoids: a systematic review.

Introduction: This review aims to provide information on return rates and times to sport following stress fractures of the great toe sesamoids (SFGTSs). Sources of data: A systematic search of CINAHAL, Cochrane, EMBASE, Google Scholar, Medline, PEDro, Scopus, SPORTDiscus and Web of Science was performed using the keywords 'stress', 'fractures', 'great', 'toe', 'sesamoid', 'athletes', 'sports', 'non-operative', 'conservative', 'operative' and 'return to sport'. Areas of agreement: Fourteen studies were included: three studies reported on the outcome of conservatively-managed SFGTSs; thirteen studies reported on the outcome of surgically-managed SFGTSs. The management principles were to attempt conservative management for 2-6 months using activity modification, analgesia, orthotics and physiotherapy; if symptoms persisted following this, surgical management was to be recommended, either with internal fixation or sesamoidectomy. Areas of controversy: The optimal treatment modalities for SFGTSs remain to be defined. Growing points: Internal fixation shows the best return to full-level sport rates with low rates of complications. Areas timely for developing research: Future prospective studies should aim to establish the optimal treatment modalities for SFGTSs.

[Ballistic concepts and management of gunshot wounds at members]. / Notions de balistique et prise en charge des plaies par balle au niveau des membres.

Ballistic trauma is not the prerogative of battlefields and currently extends to civil environments. Any surgeon or emergency room can be faced with such trauma whose management requires an understanding of wound ballistics. The aim of this retrospective is reviewing the management of ballistic trauma within the C.H.U. Saint-Pierre hospital over a period of ten years. Data recorded included demographics data, lesions, clinical parameters, imaging, treatment and outcome. It appears that the wounds of the members have a low mortality rate but a significant rate of complications. Patients should be managed according to the ATLS protocol and according hemodynamic stability and location of the injury, benefit from imaging. Unstable patients will be operated in emergency, stable patients will be treated according to the extent of damage and the type of fracture either conservatively or by external fixator and intramedullary centromedullary. Debridement and antibiotics are recommended as a nerve exploration if there is a peripheral paralysis. The management of trauma in our sample appear not optimal in light of the literature especially in terms of setting the vascular point of debridement, antibiotic and nerve repair resulting in significant consequences. Two management protocols according to patients' hemodynamic status are offered.

La traumatologie balistique n'est pas l'apanage des champs de bataille et s'étend actuellement de plus en plus aux milieux civils. Tout chirurgien ou urgentiste peut se trouver confronté à de tels traumatismes dont la prise en charge est spécifique et nécessite notamment une connaissance en balistique lésionnelle. Cette étude consiste en une revue rétrospective de la prise en charge des traumatismes balistiques au sein du C.H.U. Saint-Pierre sur une période de dix ans. Les données démographiques, lésionnelles, cliniques, d'imagerie, de traitement et de suivi ont été collectées. A l'analyse des dossiers, il ressort que les plaies des membres ont un faible taux de mortalité, mais un taux de complications non négligeable. Les patients doivent être pris en charge selon le protocole ATLS puis selon la stabilité hémodynamique et la localisation du traumatisme, bénéficier d'une imagerie. Les patients instables seront opérés en urgence sans imagerie, les patients stables présentant des traumatismes osseux seront traités selon l'importance des lésions et du type de fracture soit de manière conservatrice, soit par fixateur externe ou enclouage centro-médullaire. Un débridement et une antibiothérapie sont recommandés ainsi qu'une exploration nerveuse s'il existe une paralysie périphérique. La prise en charge des traumatismes dans notre échantillon n'apparait pas optimale à la lumière de la littérature notamment en termes de mise au point vasculaire, de débridement, d'antibiothérapie et de réparation nerveuse. Deux protocoles de prise en charge selon l'état hémodynamique du patient sont proposés afin d'optimaliser la prise en charge.

Implementing low-dose computed tomography screening for lung cancer in Canada: implications of alternative at-risk populations, screening frequency, and duration.

BACKGROUND: Low-dose computed tomography (ldct) screening has been shown to reduce mortality from lung cancer; however, the optimal screening duration and "at risk" population are not known. METHODS: The Cancer Risk Management Model developed by Statistics Canada for the Canadian Partnership Against Cancer includes a lung screening module based on data from the U.S. National Lung Screening Trial (nlst). The base-case scenario reproduces nlst outcomes with high fidelity. The impact in Canada of annual screening on the number of incident cases and life-years gained, with a wider range of age and smoking history eligibility criteria and varied participation rates, was modelled to show the magnitude of clinical benefit nationally and by province. Life-years gained, costs (discounted and undiscounted), and resource requirements were also estimated. RESULTS: In 2014, 1.4 million Canadians were eligible for screening according to nlst criteria. Over 10 years, screening would detect 12,500 more lung cancers than the expected 268,300 and would gain 9200 life-years. The computed tomography imaging requirement of 24,000-30,000 at program initiation would rise to between 87,000 and 113,000 by the 5th year of an annual nlst-like screening program. Costs would increase from approximately $75 million to $128 million at 10 years, and the cumulative cost nationally over 10 years would approach $1 billion, partially offset by a reduction in the costs of managing advanced lung cancer. CONCLUSIONS: Modelling various ways in which ldct might be implemented provides decision-makers with estimates of the effect on clinical benefit and on resource needs that clinical trial results are unable to provide.

Diagnosing lung cancer in the 21st century: are we ready to meet the challenge of individualized care?

BACKGROUND: Histologic and molecular subtyping have become increasingly important as predictors of treatment benefit in lung cancer. The objective of the present study was to determine whether current diagnostic approaches provide adequate tissue to allow for individualized treatment decisions. METHODS: Our retrospective cohort study of new lung cancer patients seen at an academic centre between July 2007 and June 2008 collected baseline demographic and diagnostic information, including mode of diagnosis, type of diagnostic material, and pathology diagnosis. RESULTS: Of the 431 study patients, 20% had stage i or ii non-small-cell lung cancer (nsclc), 24% stage iii disease, and 39% stage iv nsclc. Three quarters of the small-cell lung cancer (sclc) cases were extensive stage. Diagnostically, 18% of patients had sclc; 30%, adenocarcinoma; 27%, squamous-cell cancer; 2%, large-cell carcinoma; 1%, bronchoalveolar carcinoma; 1%, mixed histology; 18%, nsclc not otherwise specified; 4%, other; and 2%, no pathology diagnosis. Surgical pathology material was available in 80% of cases, and cytology material alone in 20%. Surgical pathology material was more common in patients with early-stage than with advanced disease (89% for stages i and ii vs. 74% for stages iii and iv, p < 0.0001). The pathology report included ambiguous terms in 24% of cases: "consistent" (12%), "suspicious" (3%), "favour" (2%), "suggestive" (2%), "likely" (1%), "compatible" with malignancy (1%), "at least" (1%), "atypical" (0.5%), and "no pathology" (1.5%). CONCLUSIONS: Current diagnostic approaches in most lung cancer patients appear adequate, but complete histopathologic identification is missing in nearly 20% of cases, and some uncertainty as to the final diagnosis is expressed in 24% of pathology reports. Some improvement in diagnostic sampling and pathology reporting are required to allow for implementation of current treatment approaches.

Survival of patients with non-small-cell lung cancer after a diagnosis of brain metastases.

BACKGROUND: The prognosis of patients with brain metastases from non-small-cell lung cancer (nsclc) is poor. However, some reports suggest that patients with brain metastases at the time of initial diagnosis have a more favourable survival than do patients with advanced nsclc without brain metastases. METHODS: In a retrospective cohort of all new lung cancer patients seen at a Canadian tertiary centre between July 2005 and June 2007, we examined survival after a diagnosis of brain metastases for patients with brain metastases at initial diagnosis and patients who developed brain metastases later in their illness. RESULTS: During the 2-year period, 91 of 878 patients (10.4%) developed brain metastases. Median age in this cohort was 64 years. In 45, brain metastases were present at initial diagnosis, and in 46, brain metastases developed later in the course of the illness. Median survival in the entire cohort was 7.8 months. Survival after the diagnosis of brain metastases was similar for patients with brain metastases at diagnosis and later in the illness (4.8 months vs. 3.7 months, p = 0.53). As a result, patients who developed brain metastases later in their illness had a longer overall survival than did patients with brain metastases at diagnosis (9.8 months vs. 4.8 months). Among patients who received chemotherapy, the survival of patients with brain metastases at diagnosis was still poor (6.2 months). CONCLUSIONS: Our data show limited survival in patients with brain metastases from nsclc. Careful patient selection for more aggressive treatment approaches is necessary.

A comparison of patient knowledge of clinical trials and trialist priorities.

BACKGROUND: Recruitment to clinical trials remains poor, and patient knowledge of clinical trials is one barrier to recruitment. To identify knowledge deficits, we conducted and compared surveys measuring actual patient knowledge and clinical trialist priorities for patient knowledge. METHODS: Consenting patients at a tertiary cancer centre answered a survey that included 2 opinion questions about their own knowledge and willingness to join a trial, and22 knowledge questions. Clinical researchers at the centre were asked 13 questions about the importance of various trials factors. RESULTS: Of 126 patients surveyed, 16% had joined a clinical trial, and 42% had a secondary school education or less. The mean correct response rate on the knowledge questions was 58%. Higher rates of correct responses were associated with lower age (p = 0.05), greater education (p = 0.006), prior trial participation (p < 0.001), agreement or strong agreement with perceived understanding of trials (p < 0.001), and willingness to join a clinical trial (p = 0.002). Trialists valued an understanding of the rationale for clinical trials and of randomization, placebo, and patient protection, but those particular topics were poorly understood by patients. CONCLUSIONS: Patient knowledge about clinical trials is poor, including knowledge of several concepts ranked important by clinical trialists. The findings suggest that when developing education interventions, emphasis should be placed on the topics most directly related to patient care, and factors such as age and education level should be considered.

Oesophageal perforation after anterior cervical surgery: management in four patients.

BACKGROUND: Oesophageal perforation related to anterior cervical surgery is an uncommon but well recognised and potentially life-threatening complication with an incidence of 0-3.4%. Our experience with this complication and a review of the literature are presented. METHOD: We retrospectively reviewed our clinical experience over 10 years and found four patients in whom an oesophageal perforation was recognised after anterior surgery for cervical spine trauma. In three patients the perforation was noticed in the early post-operative period and the other had a delayed presentation. In all patients, the hardware was removed, long-term intravenous antibiotics were administered and parenteral nutrition was instituted. In two patients a primary suture of the perforation was performed and in one of these an additional sternocleidomastoid myoplasty was carried out as well. One patient had conservative treatment and one died before closure of the perforation could be performed. FINDINGS: The two patients, in whom surgical repair of the perforation was performed, recovered well with residual neurological deficits as expected due to the cervical trauma. In the patient in whom conservative treatment was instituted, healing of the perforation occurred. One patient died due to systemic complications, indirectly related to the perforation. CONCLUSIONS: Although not very frequent and sometimes difficult to diagnose, oesophageal perforations after anterior cervical surgery constitute a potentially life-threatening complication. Diagnosis is made by imaging or endoscopic studies, but clinical suspicion is most important. Basic treatment consists of surgery with removal of hardware, drainage of abscesses, primary closure of the perforation if possible, parenteral nutrition and antibiotic therapy. Residual instability should be recognised in time and may be anticipated in patients in whom there has been little time for solid bony fusion. Successful management depends on early diagnosis and immediate institution of treatment.

Initial management of small-cell lung cancer (limited- and extensive-stage) and the role of thoracic radiotherapy and first-line chemotherapy: a systematic review.

Background: Patients with limited-stage (ls) or extensive-stage (es) small-cell lung cancer (sclc) are commonly given platinum-based chemotherapy as first-line treatment. Standard chemotherapy for patients with ls sclc includes a platinum agent such as cisplatin combined with the non-platinum agent etoposide. The objective of the present systematic review was to investigate the efficacy of adding radiotherapy to chemotherapy in patients with es sclc and to determine the appropriate timing, dose, and schedule of chemotherapy or radiation for patients with sclc. Methods: The medline and embase databases were searched for randomized controlled trials (rcts) comparing treatment with radiotherapy plus chemotherapy against treatment with chemotherapy alone in patients with es sclc. Identified rcts were also included if they compared various timings, doses, and schedules of treatment for patients with es sclc or ls sclc. Results: Sixty-four rcts were included. In patients with ls sclc, overall survival was greatest with platinum-etoposide compared with other chemotherapy regimens. In patients with es sclc, overall survival was greatest with chemotherapy containing platinum-irinotecan than with chemotherapy containing platinum-etoposide (hazard ratio: 0.84; 95% confidence interval: 0.74 to 0.95; p = 0.006). The addition of radiation to chemotherapy for patients with es sclc showed mixed results. There was no conclusive evidence that the timing, dose, or schedule of thoracic radiation affected treatment outcomes in sclc. Conclusions: In patients with ls sclc, cisplatin-etoposide plus radiotherapy should remain the standard therapy. In patients with es sclc, the evidence is insufficient to recommend the addition of radiotherapy to chemotherapy as standard practice to improve overall survival. However, on a case-by-case basis, radiotherapy might be added to reduce local recurrence. The most commonly used chemotherapy is platinum-etoposide; however, platinum-irinotecan can be considered.

Resource use in the last three months of life by lung cancer patients in southern Ontario.

Background: End-of-life cancer care involves multidisciplinary teams working in various settings. Evaluating the quality of care and the feedback from such processes is an important aspect of health care quality improvement. Our retrospective cohort study reviewed health care use by lung cancer patients at end of life, their reasons for visiting the emergency department (ed), and feedback from regional health care professionals. Methods: We assessed 162 Ontario patients with small-cell and relapsed or advanced non-small-cell lung cancer. Demographics, disease characteristics, and resource use were collected, and the consenting caregivers for patients with ed visits were interviewed. Study results were disseminated, and feedback about barriers to care was sought. Results: Median patient age was 69 years; 73% of the group had non-small-cell lung cancer; and 39% and 69% had received chemotherapy and radiation therapy respectively. Median overall survival was 5.6 months. In the last 3 months of life, 93% of the study patients had visited an oncologist, 67% had telephoned their oncology team, 86% had received homecare, and 73% had visited the ed. Death occurred for 55% of the patients in hospital; 23%, at home; and 22%, in hospice. Goals of care had been documented for 68% of the patients. Homecare for longer than 3 months was associated with fewer ed visits (80.3% vs. 62.1%, p = 0.022). Key themes from stakeholders included the need for more resources and for effective communication between care teams. Conclusions: Use of acute-care services and rates of death in an acute-care facility are both high for lung cancer patients approaching end of life. In our study, interprofessional and patient-provider communication, earlier connection to homecare services, and improved access to community care were highlighted as having the potential to lower the need for acute-care resources.

Lateral safety limits during a facial transclival approach to the craniovertebral junction.

BACKGROUND: Transclival procedures are infrequently performed and carry some dangerous complications. The carotid arteries and the hypoglossal nerves are the most important structures at risk during the subperiostal lateral dissection of the posterior wall of the oropharynx. These lateral landmarks are, however, not easily identified during the surgical dissection. METHODS: We measured the location of the foramen lacerum externum and the hypoglossal canal with respect to the midline. These measurements were performed on 76 non-pathological CT-scanned skulls that were converted into accurate three-dimensional digital reconstruction models by the use of 3D image-processing. The same measurements were also taken on 15 non-pathological skulls by the use of a slide calliper. RESULTS: For the foramen lacerum, the distance to the midline was 11 mm +/- 1 mm SD (range 8-14 mm) on the right-hand side and 11 mm +/- 1 mm SD (range 9-14 mm) on the left-hand side. For the right hypoglossal canal this distance was 17 mm +/- 1 mm SD (range 15-22 mm) and for the left hypoglossal canal 17 mm +/- 1 mm SD (range 14-20 mm). There was no significant difference between left and right. CONCLUSION: The posterior wall of the oropharynx can be safely dissected for at least 8 mm from the midline at the level of the foramen lacerum and for at least 14 mm towards the hypoglossal canal from the midline at the level of the anterior border of the foramen magnum. In addition, this technique with the help of 3D software, can be very useful in the pre-operative setting when performing complex skull base procedures.

Guideline for the Initial Management of Small Cell Lung Cancer (Limited and Extensive Stage) and the Role of Thoracic Radiotherapy and First-line Chemotherapy.

AIMS: We investigated the efficacy of adding radiotherapy to chemotherapy in patients with extensive stage small cell lung cancer (ES-SCLC) and the appropriate timing, dose and schedule of treatment for patients with ES-SCLC or limited stage SCLC (LS-SCLC). MATERIALS AND METHODS: The guideline was developed by Cancer Care Ontario's Program in Evidence-Based Care and by the Lung Cancer Disease Site Group through a systematic review of randomised controlled trials. KEY RECOMMENDATIONS: In patients with LS-SCLC (stage I, II and III), the addition of thoracic radiotherapy to standard chemotherapy is recommended. However, there is no clear evidence to inform definitive recommendations for optimal timing, sequential versus concurrent therapies and optimal dose or regimen. In patients with LS-SCLC, etoposide-cisplatin is the preferred regimen for adults who are being treated with combined modality therapy with curative intent. In patients with ES-SCLC (stage IV), there is insufficient evidence to recommend the addition of thoracic radiotherapy to standard chemotherapy as a standard practice for survival benefit; however, it could be considered on a case-by-case basis to reduce local recurrence. In patients with ES-SCLC, a platinum agent plus etoposide is the preferred regimen for adult patients who are being treated with combined modality therapy. Cisplatin and irinotecan represents an alternative treatment option to this, but is associated with increased rates of adverse events such as diarrhoea.

A new test set-up for skull fracture characterisation.

Skull fracture is a frequently observed type of severe head injury. Historically, a variety of impact test set-ups and techniques have been used for investigating skull fracture. The most frequently used are the free-fall technique, the guided fall or drop tower set-up and the piston-driven impactor set-up. This document proposes a new type of set-up for cadaver head impact testing which combines the strengths of the most frequently used techniques and devices. The set-up consists of two pendulums, which allow for a 1 degree of freedom rotational motion. The first pendulum is the impactor and is used to strike the blow. The head is attached to the second pendulum using a polyester resin. Local skull deformation and impact force are measured with a sample frequency of 65 kHz. From these data, absorbed energy until skull fracture is calculated. A set-up evaluation consisting of 14 frontal skull and head impact tests shows an accurate measurement of both force and local skull deformation until fracture of the skull. Simplified mechanical models are used to analyse the different impacting techniques from literature as well as the new proposed set-up. It is concluded that the proposed test set-up is able to accurately calculate the energy absorbed by the skull until fracture with an uncertainty interval of 10%. Second, it is concluded that skull fracture caused by blunt impact occurs before any significant motion of the head. The two-pendulum set-up is the first head impact device to allow a well-controlled measurement environment without altering the skull stress distribution.

[11C]methionine PET, histopathology, and survival in primary brain tumors and recurrence.

BACKGROUND AND PURPOSE: [(11)C]Methionine (MET) PET imaging is a sensitive technique for visualizing primary brain tumors and recurrence/progression after therapy. The aim of this study was to evaluate the relationship between the uptake of MET and histopathologic grading and to investigate the prognostic value of the tracer, in both settings. METHODS: Cerebral uptake of MET was determined in 52 patients: in 26 patients for primary staging (group A) and 26 patients with suspected brain tumor recurrence/progression after therapy (group B). Semiquantitative methionine uptake indices (UI) defined by the tumor (maximum)-to-background ratio was correlated with tumor grade and final outcome. RESULTS: Overall median survival was 34.9 months. MET showed pathologically increased uptake in 41 of 52 scans. Although a weak linear correlation between MET uptake and grading was observed (R = 0.38, P = .028), analysis of variance showed no significant differences in MET UI between tumor grades for either group A or B. Benign and grade I lesions showed significant difference in MET uptake in comparison with higher grade lesions (P = .006). Using Kaplan-Meier survival analysis, no thresholds could be found at which MET was predictive for survival. Proportional hazard regression showed that only WHO grading class (low versus high) was predictive of survival (P = .015). CONCLUSION: Interindividual MET uptake variability does not allow noninvasive grading on an individual patient basis. Moreover, there is no significant prognostic value in studying maximal methionine UI in brain tumors. The clinical use of MET should therefore be primarily focused on questions such as detection of recurrence, biopsy guidance, and radiation therapy target volume delineation.

Risk analysis of thrombo-embolic and recurrent bleeding events in the management of intracranial haemorrhage due to oral anticoagulation.

PURPOSES: Intracranial haemorrhage (ICH) is a rare but potentially devastating complication of oral anticoagulants (OAC). This raises the difficult clinical choice between either permanent cessation of OAC, or continuing OAC and if so, when to restart. To make this choice, one needs to balance the thrombo-embolic risk after cessation of OAC against the risk of recurrent intracranial haemorrhage when OAC are restarted. There are few published data to base this difficult clinical decision on. METHODS: We present an observational study of a consecutive series of 108 patients, collected prospectively and admitted to our department, with an OAC-related intracranial haemorrhage, in whom we assessed the thrombotic event rate and the recurrent intracranial bleeding rate during follow-up. RESULTS: In the 25 patients in whom OAC were reinstituted no new thrombo-embolic events occurred (0/506 unprotected patient-days). In the group of patients in whom OAC were not restarted (n = 81), the thrombo-embolic event rate was 8/11590 unprotected patient-days, of which only 2 were cerebrovascular thrombo-embolisms. The overall risk of a thrombo-embolic complication can be estimated to be 0.66 events/1000 patient-days at risk (95% exact confidence limits of 0.3 to 1.3 events/1000 patient-days at risk). In three patients the thrombo-embolic event was fatal. We saw recurrent intracranial bleeding in eight patients, 2 of which were fatal. Seven of these occurred before the restarting of the OAC. CONCLUSIONS: In OAC-related intracranial haemorrhages, OAC can be stopped safely for a considerable period, with a very low overall thrombotic event rate. The recurrent bleeding risk after restarting OAC is low. Recurrent bleeding mostly occurred before restarting OAC and is probably caused by insufficient or unsustained correction of the initial coagulation deficit. Immediate reversal of anticoagulation provides the patient with the best possible treatment options including surgery. OAC-related intracranial haemorrhages can therefore be actively treated.

Upper airway obstruction caused by a cervical osteophyte.

A case of severe acute upper airway obstruction caused by a cervical osteophyte requiring urgent tracheostomy is presented. The patient was treated successfully by resection of the osteophyte followed by cervical fusion.

Evaluation of exogenous surfactant treatment strategies in an adult model of acute lung injury.

Two exogenous surfactant preparations [Survanta and bovine lipid extract surfactant (BLES)] were evaluated in saline lavage-injured adult sheep with two different delivery methods (instillation vs. aerosolization). Instilled BLES resulted in the greatest improvement in lung function, followed by aerosolized Survanta and then instilled Survanta. Aerosolized BLES was ineffective. Total surfactant recovery and distribution patterns were similar for Survanta and BLES for each delivery method tested. There were significant differences, however, in the proportion of surfactant recovered in the alveolar wash relative to the lung tissue between the groups at killing. Moreover, the ratio of poorly functioning small surfactant aggregates to superior functioning large aggregates isolated from alveolar wash samples correlated with the physiological responses. The calculated contribution of secreted endogenous surfactant to the total alveolar phospholipid pool at killing was significantly greater for the aerosolized Survanta group compared with the aerosolized BLES group. This finding suggested that there were differences in the interaction of the exogenous surfactants and their alveolar environments. We conclude that the response to exogenous surfactant in acute lung injury depends not only on the preparation used but also on how the surfactants are delivered to the injured lung.

Timing of exogenous surfactant administration in a rabbit model of acute lung injury.

The purpose of this study was to evaluate early vs. late administration of exogenous surfactant in an adult rabbit model of acute lung injury. Lung injury was induced by repetitive whole lung saline lavage and subsequent mechanical ventilation. Bovine lipid extract surfactant was instilled either 1 (Early) or 4 h (Late) after the last lavage. Animals were monitored for 7 h after the last lavage. Although arterial PO2 values increased significantly immediately after treatment in both the Early and Late groups, this improvement was not sustained in the Late group. There was also a higher incidence of pneumothoraxes in the Late group vs. both the Early group and a nontreated control group. The ratio of poorly functioning small surfactant aggregates to superior functioning large aggregates was higher in the Late group compared with the Early group. Morphological analysis revealed that early surfactant treatment prevented the progression of lung injury over time. We conclude that administration of exogenous surfactant at an early time point in lung injury resulted in superior responses compared with later treatments.

Simultaneous occurrence of developmental venous anomalies and cavernous angiomas.

PURPOSE: To study the clinical and radiologic findings in 15 patients presenting with both developmental venous anomalies and cavernous angiomas and to determine which lesions caused the acute clinical symptoms. METHODS: Lesions were infratentorial in 7 patients and supratentorial in 7 other patients. In one patient the developmental venous anomaly was infratentorial and the cavernous angioma supratentorial. In all 15 patients clinical examination and CT were performed. In 10 patients MR was performed at the time of the initial CT scan. In 5 patients only late MR is available. RESULTS: Acute clinical signs were present in 9 patients (epilepsy, hemiplegia, meningeal signs, cranial nerve deficit). On CT the cavernous angioma was missed in 9 patients, in 6 patients because of acute hemorrhage. On MR the cavernous angioma was missed in 1 of 2 cases with acute hemorrhage but seen in all other patients. On repeat MR all cavernous angiomas were correctly identified. On CT, 11 developmental venous anomalies were seen. On MR all developmental venous anomalies were seen. CONCLUSIONS: The frequent association of developmental venous anomalies and cavernous angiomas is confirmed. MR is superior to CT in the detection of both cavernous angiomas and developmental venous anomalies. Furthermore our data support the hypothesis that cavernous angiomas and not the developmental venous anomalies cause the acute clinical symptoms because of hemorrhage.

Endovascular treatment of a ruptured paraclinoid aneurysm of the carotid syphon achieved using endovascular stent and endosaccular coil placement.

We herein report a case of a ruptured superior hypophyseal aneurysm of the left supraclinoid carotid artery that could not be treated with a Guglielmi detachable coil (GDC), even in combination with a supporting nondetachable balloon. After an unsuccessful attempt at surgical clipping, treatment consisted of the placement of a stent over the neck of the aneurysm, advancement of a microcatheter through the stent mesh, and endosaccular embolization with a GDC. The late clinical outcome was excellent.