Surgical resection versus watchful waiting in low-grade gliomas.

BACKGROUND: Infiltrating low-grade gliomas (LGG; WHO grade 2) typically present with seizures in young adults. LGGs grow continuously and usually transform to higher grade of malignancy, eventually causing progressive disability and premature death. The effect of up-front surgery has been controversial and the impact of molecular biology on the effect of surgery is unknown. We now present long-term results of upfront surgical resection compared with watchful waiting in light of recently established molecular markers. MATERIALS AND METHODS: Population-based parallel cohorts were followed from two Norwegian university hospitals with different surgical treatment strategies and defined geographical catchment regions. In region A watchful waiting was favored while early resection was favored in region B. Thus, the treatment strategy in individual patients depended on their residential address. The inclusion criteria were histopathological diagnosis of supratentorial LGG from 1998 through 2009 in patients 18 years or older. Follow-up ended 1 January 2016. Making regional comparisons, the primary end-point was overall survival. RESULTS: A total of 153 patients (66 from region A, 87 from region B) were included. Early resection was carried out in 19 (29%) patients in region A compared with 75 (86%) patients in region B. Overall survival was 5.8 years (95% CI 4.5-7.2) in region A compared with 14.4 years (95% CI 10.4-18.5) in region B (P < 0.01). The effect of surgical strategy remained after adjustment for molecular markers (P = 0.001). CONCLUSION: In parallel population-based cohorts of LGGs, early surgical resection resulted in a clinical relevant survival benefit. The effect on survival persisted after adjustment for molecular markers.

Surgery for chronic subdural hematoma in nonagenarians: A Scandinavian population-based multicenter study.

OBJECTIVE: Chronic subdural hematoma (cSDH) is a prevalent condition often seen in the elderly, with surgery being the treatment of choice when symptomatic. So far, few have explored the surgical outcomes in patients 90 years or older. The aim of this study was to investigate outcome after cSDH surgery in nonagenarians (≥90 y/o group) compared to younger adult patients (<90 y/o group). MATERIALS: In a Scandinavian population-based cohort we conducted a retrospective review of 1,254 patients undergoing primary burr-hole procedures for cSDH between January 1, 2005 and December 31, 2010 at three neurosurgical centers. In a comparative analysis, the primary end-point was difference in hematoma recurrence rates between the ≥90 y/o and <90 y/o groups. The secondary end-points were differences in perioperative morbidity and mortality between groups. RESULTS: 75 patients were 90 years or older. There was no significant difference in recurrences resulting in reoperation between the age groups (10.7% vs 13.6%, P=.47). There was also no significant difference in overall complication rate (4.1% vs 8.1%, P=.21) or severe complications (1.4% vs 2.0%, P=.68). There were three (4.0%) perioperative deaths within 30 days in the ≥90 y/o group and 40 (3.4%) in the <90 y/o group (P=.78). CONCLUSION: Patients 90 years or older had similar rates of recurrence, perioperative morbidity and perioperative mortality as compared to younger patients. Age alone should not be a contraindication for surgery in patients with cSDH.

Fertility and gonadal function after adjuvant therapy in women diagnosed with a malignant ovarian germ cell tumor (MOGCT) during the "cisplatin era".

PURPOSE: By self-report and serum levels of anti-Mullerian hormone (AMH) this study aims to assess post-treatment fertility after modern treatment of women with malignant ovarian germ cell tumors (MOGCT). PATIENTS AND METHODS: In 2013 a questionnaire-based survey was performed in 61 MOGCT patients diagnosed at age <40years from 1980-2009. Forty-nine of them also attended the out-patient clinic. The event of first post-treatment pregnancy ("fertility") was documented as cumulative estimates for all 61 patients and within each of 4 treatment groups: Group 1: Surgery only (n=10); Group 2: ≤3cycles of cisplatin-based chemotherapy (CBCT) (n=20); Group 3: >3cycles of CBCT (n=15) and Group 4: other adjuvant treatment (n=16). AMH was determined in 22 women <40years at survey. Statistics were based on Kaplan Meier procedure, log-rank test and a significance level p<0.05. RESULTS: At least one post-treatment pregnancy was reported by 34 of 39 MOGCT survivors who attempted motherhood after treatment. The 15-year cumulative post-treatment fertility estimate was 28% (95% CI: 26-30) for all 61 survivors and was significantly higher in patients treated with 3 or fewer cycles of CBCT (53% [95% CI: 50-55]) than those treated with more than 3cycles (20% [95% CI: 17-22]) (P=0.03). Of 22 AMH levels, two were <3pmol/l, with one women being pregnant at survey. CONCLUSION: After fertility-sparing surgery and modern cisplatin-based chemotherapy, fertility is preserved in most MOGCT survivors though dependent on the number of cycles. AMH's role as a biomarker of gonadal function seems promising but requires further research.

Malignant ovarian germ cell tumors: presentation, survival and second cancer in a population based Norwegian cohort (1953-2009).

PURPOSE: To quantify and compare survival in women with malignant ovarian germ cell tumors (MOGCTs) in Norway before and after the introduction of cisplatin-based chemotherapy (around 1980), and to explore the association between different types of treatment and the development of a second cancer. PATIENTS AND METHODS: We identified 351 patients diagnosed with MOGCTs from 1953 to 2009 in the Cancer Registry of Norway. Ovarian cancer-specific survival was calculated separately for patients diagnosed before and after 1980. Patients were divided into subgroups by histological subtype (pure dysgerminoma, malignant teratoma, other MOGCTs) and extent of disease (localized and metastatic). We estimated the cumulative incidence of a second cancer in 10-year MOGCT survivors. Kaplan-Meier estimates were used, and p<0.05 was considered significant. RESULTS: 20-Year ovarian cancer-specific survival increased from 59% (95% CI 51% to 66%) before 1980 to 88% (95% CI 83%-93%) thereafter. Significant improvement was observed in all subgroups. No second cancer was diagnosed in any of 31 10-year MOGCT survivors treated with surgery only; second cancer was diagnosed in 23 of 139 patients who underwent cytotoxic treatment (98 radiotherapy ± chemotherapy, 41 chemotherapy only; p=0.08). Patients aged >50 years had a significantly poorer ovarian cancer-specific survival than younger patients (HR=5.98, 95% CI 3.39-10.57) after adjustment for histological subtype and stage at presentation. Our results favor the treatment of patients with metastatic MOGCTs at large cancer centers. CONCLUSION: Today women with MOGCTs have an excellent prognosis if treated according to modern therapeutic principles.

A method for estimating the fibre length in fibre-PLA composites.

Wood pulp fibres are an important component of environmentally sound and renewable fibre-reinforced composite materials. The high aspect ratio of pulp fibres is an essential property with respect to the mechanical properties a given composite material can achieve. The length of pulp fibres is affected by composite processing operations. This thus emphasizes the importance of assessing the pulp fibre length and how this may be affected by a given process for manufacturing composites. In this work a new method for measuring the length distribution of fibres and fibre fragments has been developed. The method is based on; (i) dissolving the composites, (ii) preparing the fibres for image acquisition and (iii) image analysis of the resulting fibre structures. The image analysis part is relatively simple to implement and is based on images acquired with a desktop scanner and a new ImageJ plugin. The quantification of fibre length has demonstrated the fibre shortening effect because of an extrusion process and subsequent injection moulding. Fibres with original lengths of >1 mm where shortened to fibre fragments with length of <200 µm. The shortening seems to be affected by the number of times the fibres have passed through the extruder, the amount of chain extender and the fraction of fibres in the polymer matrix.

Surgical resection of brain metastases: the prognostic value of the graded prognostic assessment score.

There is a need for better predictors for short survival in patients with brain metastases undergoing open surgery. The graded prognostic assessment (GPA) has recently been developed to predict survival in patients with brain metastases. We explored the prognostic capabilities of GPA in a consecutive neurosurgical population of brain metastases. Secondarily, we evaluated if GPA scores can provide information on safety of the operation and postoperative functional outcome. We retrospectively included all adult (≥ 18 years) patients undergoing open surgery for brain metastases from 2004 through 2009 (n = 141). The population was grouped into GPA 0-1 (n = 22, 16%), GPA 1.5-2.5 (n = 90, 64%), GPA 3 (n = 19, 14%), and GPA 3.5-4 (n = 10, 7%) according to the prognostic indices. Median survival times were 6.3 months (range 0.8-23.7) in GPA 0-1, 7.8 months in GPA 1.5-2.5 (range 0.2-75.0), 14.0 months in GPA 3 (range 0.0-77.4), and 18.4 months in GPA 3.5-4 (range 0.1-63.7). This represents a significant difference between groups (P = 0.010). There were no associations between GPA and 30-day mortality (P = 0.871), 3-month mortality (P = 0.750), complications (P = 0.330) or change in Karnofsky Performance status postoperatively (P = 0.558). GPA scores hold prognostic properties in patients operated for brain metastases. However, GPA did not predict short-term mortality, limiting the clinical usefulness in a neurosurgical population. The prognostic indices cannot be used alone to decide if surgery is warranted on an individual basis, or to evaluate risks and benefits of surgery.

Integrated pre- and intraoperative imaging in a patient with an arteriovenous malformation located in eloquent cortex.

INTRODUCTION: The use of integrated pre- and intraoperative imaging may be useful when resecting brain lesions in close proximity to eloquent areas, such as the primary motor cortex and language cortices. CASE REPORT: A 32-year-old woman with an arteriovenous malformation (AVM) located in the primary motor cortex underwent surgery using functional neuronavigation. Blood-oxygenation-level-dependent functional magnetic resonance imaging (BOLD fMRI) and diffusion tensor tractography (DTT) were used for preoperative mapping of primary motor areas and the corticospinal tracts, respectively. The BOLD fMRI activations and DTT tractograms were integrated into the neuronavigation system and visualized intraoperatively throughout the operation. Furthermore, stereoscopic visualizations of the angioarchitecture based on 3D MRI angiograms were used to rehearse the surgical approach to the feeder vessels. Finally, intraoperative ultrasound was used to locate and clip the feeding vessels. CONCLUSION: The AVM was carefully resected with the aid of the above-mentioned imaging techniques, and the intuitive usefulness of the techniques was further substantiated by the rewarding postoperative outcome.

Rapid and severe rise in static and pulsatile intracranial pressures during a generalized epileptic seizure.

In a patient with no prior history of seizures we were able to record static (mean) intracranial pressure (ICP) and pulsatile ICP (mean ICP wave amplitude) continuously during a first-time generalized epileptic seizure. The patient experienced episodic headache five months after a subarachnoid haemorrhage. In order to rule out low-pressure hydrocephalus she was admitted for a 24-hour intracranial pressure registration. ICP parameters were normal prior to the seizure. We observed an immediate and enormous rise in both static (mean) ICP and pulsatile ICP (mean ICP wave amplitude). Mean ICP and ICP wave amplitude peaked at 93 mmHg and 22 mmHg, respectively. Pulsatile ICP remained elevated after normalization of static ICP and may indicate impairment of intracranial compliance even after the static ICP was normalized.

Quality of life in adult patients with primary intracranial arachnoid cysts.

BACKGROUND: Primary arachnoid cysts are benign developmental lesions of arachnoid mater. Arachnoid cysts may be detected due to various neurological symptoms, or they may be encountered as incidental findings of neuroimaging. Consequently, a significant share of the patients seems asymptomatic. There are diverging opinions about the clinical importance of cyst sizes, cyst location and degree of volume reduction after surgery, hence contributing to controversies regarding indications for surgical treatment. We present the first study assessing internationally established parameters of quality of life and mental health in a clinical-outcome analysis of adult patients with arachnoid cysts. METHOD: Ninety-two adult patients with arachnoid cysts who had been referred to our department over the last 16 years were included. Forty-seven patients had undergone surgery and 45 patients had not been operated on. Data for analysis was based on both medical records and questionnaires sent out by mail. Quality of life was assessed by the Short Form 36 Health Survey (SF-36), and mental health was further evaluated by the Hospital Anxiety and Depression Scale (HADS). Seventy-one percent of patients responded to our questionnaires. FINDINGS: There was a great variation in the presenting symptoms, seemingly without any relation to cyst localisation. Patients with arachnoid cysts seem to have a reduced quality of life and a very high prevalence of anxiety compared to a healthy normal population. Men presented lower outcome scores than women. Subjects with symptoms, that we retrospectively labeled biologically comprehensible, tended to have higher quality of life, less anxiety and better subjective symptom relief after surgery. CONCLUSION: Our arachnoid cyst population had a low employment status, decreased quality of life scores and prevalent symptoms of anxiety. We argue that the arachnoid cysts are, in most cases, not directly related to these studied parameters. We speculate that our findings may reflect the demographic characteristics of adults likely of being diagnosed with incidental cysts. A better clinical outcome for patients with biologically plausible symptoms supports a neurobiological approach in the selection of patients suited for surgery.

Maximising biogas in anaerobic digestion by using engine waste heat for thermal hydrolysis pre-treatment of sludge.

Dublin's Ringsend WWTP was designed to serve a population of approximately 1.2 million p.e. with a sludge production of 37,000 dry tonnes per year after upgrading to full secondary treatment. Several technical solutions were put forward as part of a design, build, finance and operate (DBFO) competition, with the chosen solution being a proposal by Black and Veatch for a combination of sequencing batch reactor (SBR) technology and anaerobic digestion with Cambi thermal hydrolysis pre-treatment (THP). The THP plant was built by Cambi and handed over to B&V in 2002. The plant is now operated by Celtic Anglian Water. In September 2004 a test was carried out on the mass and energy balance of the plant following 2 years of operation and is detailed in this paper. The process enables digestion at very high dry solids feed and low hydraulic retention time. The plant was built with three digesters of 4250 m3 each and is fed with hydrolysed sludge at 11% DS. There are four no. 1 MW Jenbacher engines operating mainly on biogas. Each pair of engines is fitted with a waste heat boiler with a capacity of one tonne steam per hour. These boilers have sufficient capacity to provide 80% of the steam required for the THP, which in turn provides all the heat for the subsequent digestion in the form of hydrolysed feed. There are two main biogas boilers for top up steam and other uses of the biogas including thermal oxidation of concentrated odours.

Treatment of osteosarcoma of the extremities with the T-10 protocol, with emphasis on the effects of preoperative chemotherapy with single-agent high-dose methotrexate: a Scandinavian Sarcoma Group study.

From 1982 to 1989, 97 patients with extremity-localized, high-grade osteosarcoma were treated according to the T-10 protocol. Two thirds of the patients consisted of the near-complete national patient materials from Norway and Finland. Eighty patients (82%) received four courses of high-dose methotrexate (HD MTX, 8 to 12 g/m2) at weekly intervals as their only preoperative treatment, and 77 patients (79%) were assessable for histologic response grading according to Rosen et al (Cancer 49:1221-1230, 1991). Observed histologic response was no certain chemotherapy effect (grade I) in 21%, grade II effect in 62%, and grade III or IV effect in 17%. Nonresponders had significantly lower serum MTX concentrations after 24 and 48 hours than responders; the significance of the difference at 48 hours was maintained in a multivariate analysis. After a median follow-up of 45 months, projected 5-year overall and relapse-free survival for all patients were 64% and 54%, respectively. Patients with a good response to preoperative chemotherapy (grade III/IV) had a significantly better survival than grade I/II responders, despite a switch to postoperative cisplatin/doxorubicin chemotherapy in the latter group. These results were obtained in a largely nonselected group of patients. We conclude that a good initial chemotherapy effect is important for the final outcome in osteosarcoma, and that HD MTX alone is insufficient preoperative treatment for the majority of patients. The individual MTX excretion rate is of importance for tumor response, suggesting a dose-response relationship for HD MTX treatment.

Adjuvant chemotherapy with doxorubicin in high-grade soft tissue sarcoma: a randomized trial of the Scandinavian Sarcoma Group.

From January 1981 to February 1986, a total of 240 patients with primary, malignancy-grade III or IV soft tissue sarcoma were entered into an adjuvant chemotherapy multicenter trial conducted by the Scandinavian Sarcoma Group (SSG). Of these patients, 181 were evaluable. The tumor was located in the extremities in 155 patients. After radical surgery (wide and compartmental) the patients were randomized to treatment with single-agent doxorubicin 60 mg/m2 administered as an intravenous (IV) bolus once a month for 9 months (group 1, n = 77) or to control (group 2, n = 77). If the surgical procedure was marginal, the patients initially received postoperative radiotherapy, followed by doxorubicin (group 3, n = 16) or control (group 4, n = 11). The control groups did not receive any adjuvant chemotherapy. Adjuvant therapy was initiated within 6 weeks of surgery (group 1) or within 10 weeks of surgery for patients receiving postoperative radiotherapy (group 3). With a median follow-up of 40 months, there was no significant difference between the four treatment groups in overall survival (group 1, 75%; group 2, 70%; group 3, 69%; group 4, 73%), disease-free survival (group 1, 62%; group 2, 56%; group 3, 62%; group 4, 64%), or local tumor control (group 1, 92%; group 2, 92%; group 3, 87%; group 4, 90%). The conclusions were the same whether the total group or evaluable patients only were included in the analysis. The local recurrence rate for patients undergoing radical surgery was 8% and for patients undergoing marginal surgery followed by radiotherapy was 12%. This study indicates that the use of single-agent doxorubicin as postoperative adjuvant chemotherapy has no significant clinical benefit in patients with high-grade soft tissue sarcoma.

Immunoscintigraphy of bone sarcomas--results in 5 patients.

The feasibility of using the murine monoclonal antibody, TP-1, for clinical immunoscintigraphy was examined in a pilot study involving 5 patients with bone sarcomas. 131I-labelled F(ab')2 antibody fragments were injected in doses of 0.8-1.0 mg (90-130 MBq), and the accumulation of radioactivity was examined by scintigraphy, and assessed by direct measurements on biopsied tumour and normal tissue. One osteosarcoma patient had a primary tumour in the femur, whereas the other 4 had single lung metastases detected by other diagnostic methods. Immunoscintigraphy of the femoral primary was optimally visualised after 22 h. In 2 patients, the method failed to detect lung metastasis, in 1 of the cases possibly related to less than optimal methodological conditions. In 2 other patients, increased accumulation of radioactivity indicated one and three lung tumours, in addition to the single metastasis observed by X-ray and CT scanning, tumours that were later confirmed and removed surgically. The concentration of radioactivity in tumour and normal tissues 44-72 h after antibody injection could be measured in 4 patients. The tumour to blood ratios were in the range of 1.2-4.2, compared to 0.1-0.8 for various normal tissues. The results indicate that immunoscintigraphy with TP-1 antibody fragments have a potential for early detection of lung metastases in patients with bone sarcoma.

Ifosfamide and continuous infusion etoposide in advanced adult soft tissue sarcoma. A Scandinavian Sarcoma Group Phase II Study.

The purpose of this study was to evaluate tumour response and toxicity to ifosfamide and continuous infusion etoposide in metastatic or locally advanced soft tissue sarcoma, with dose escalations under G-CSF (granulocyte colony-stimulating factor) support. Of 92 eligible patients (median age 51 years), 85% had tumours of high-grade malignancy and 82% had metastatic disease. Chemotherapy, the baseline dose, consisted of etoposide 600 mg/m2 as a 72 h infusion and ifosfamide 1500 mg/ m2/day for 3 days, followed by G-CSF support (VIG regimen). Stepwise 10% dose escalations were performed depending on haematological toxicity. For patients considered operable after induction chemotherapy, surgical resection of all identifiable residual tumour was attempted. Complete and partial response rates were 11% and 31%, for an overall response rate of 42% (95% CI 31-52%). Forty-eight per cent of courses were dose escalated by a median of 20%. Complete responders had significantly higher, and patients with progressive disease had significantly lower, dose levels than other patients. None of 20 patients with liver metastases responded despite high dose levels. Compared to a preceding pilot study, the addition of G-CSF led to significantly higher dose levels, improved schedule adherence and less haematological toxicity, but no apparent increase in response rate. In view of the modest dose of ifosfamide applied in this study, it is possible that the prolonged infusion of etoposide made a significant contribution to the regimen's antitumour activity, although this can only be determined definitively in a randomised study.

Treatment of advanced, high-grade soft-tissue sarcoma with ifosfamide and continuous-infusion etoposide.

A total of 33 patients (median age, 44 years) with high-grade, adult soft-tissue sarcoma were treated with etoposide given at 600 mg/m2 in a 72-h continuous infusion and ifosfamide given at 1500 mg/m2 per day for 3 days every 3 weeks. Dose escalation/reduction was protocolled depending on the level of hematological toxicity observed in the preceding course. Overall, 90% of patients had metastatic disease, and the most common histologies were malignant fibrous histiocytoma and leiomyosarcoma. A median of 5 (range, 1-9) courses were given. Of 30 patients who were evaluable for response, 12 (40%) obtained a partial remission, and the median time to progression was 8 (range, 4-13) months. Grade 3-4 leukopenia and thrombocytopenia were seen after 89% and 8% of the courses, respectively; neutropenic fever was seen in half of the patients (15% of courses); and 32% of courses had to be postponed by 7 days or more due to myelosuppression. Dose reduction to below the standard had to be performed in 46% of courses, and dose escalation was achieved in only 13%. The reduced toxicity seen after the addition of granulocyte colony-stimulating factor (G-CSF) in five patients indicates that growth-factor support may enhance the dose intensity of the regimen. The results indicate significant activity for this regimen in adult soft-tissue sarcoma, which may in part be a result of the escalated dose and prolonged mode of administration of the phase-specific agent etoposide. As a result of this pilot series, a phase II study with ifosfamide, etoposide, and G-CSF in advanced adult soft-tissue sarcoma has been initiated by the Scandinavian Sarcoma Group.

Synovial sarcoma: immunohistochemical expression of P-glycoprotein and glutathione S transferase-pi and clinical drug resistance.

Our purpose was to study the role of the expression of P-glycoprotein (Pgp) and glutathione S transferase-pi (GST-pi) in predicting the response to chemotherapy, relapse-free interval, and survival of patients with synovial sarcoma (SS). Thirty-seven cases of primary SS, without regional lymph node or distant metastases, were studied. There were 17 females and 20 males, ranging in age from 7 to 81 years (median, 31 years) with tumors located in the lower extremity (n = 24) upper extremity (n = 5) and trunchus (n = 8). The cases were retrospectively studied without knowledge of clinical course to compare the immunohistochemical expression of Pgp and GST-pi, flow cytometry parameters (ploidy and % of cells in S+G2 phases), and PCNA and Ki-67 labeling of primary tumors before any therapy, with that observed in local recurrences and metastases after chemotherapy. The relationship of the aforementioned parameters with clinicopathological features (gender, age, and histo-blood group of the patients, size, location, histological subtype. TNM stage, and clinical response to chemotherapy of the tumors) was also evaluated. Results revealed that Pgp and GST-pi were expressed in 29.7% and 40.5% of the cases, respectively. In 48.6% of the tumors there was expression of a least one of the drug resistance markers. The markers were coexpressed in 25.0% of the tumors. The prevalence of Pgp expression was lower, but not significantly, in stage I-II (17.6%) than in stage III (40.0%) tumors, and also in cases without clinical progression (16.7%), than in cases with (36.0%). No such differences were observed for GST-pi expression. Pgp and GST-pi expressions were significantly associated with biphasic SS and were particularly noticeable in solid/glandular areas of biphasic SS. The expression of the drug resistance markers was not significantly associated with gender, age, and histo-blood group of the patients, dimension, location, and proliferative activity of the tumors; it was also not significantly related to relapse-free interval and survival of the patients. The expression of Pgp and GST-pi was not significantly associated either to response to chemotherapy or influenced by chemotherapy. We conclude that Pgp and GST-pi expressions are not good predictors response to of the chemotherapy in patients with localized SS. Other drug resistance mechanisms may be active in SS.

Prognostic factors in bone sarcomas.

Based on a literature review and the SSG experience, the most important prognostic factors in high-grade osteosarcoma appear to be the presence of detectable metastases at diagnosis, tumour volume, old age, sex, histologic response, and possibly tumoral P-glycoprotein expression. However, for an adolescent patient with non-metastatic extremity disease, there is no consensus regarding prognostic factors at initial presentation, and currently there is thus no established method for dividing them into high- and low risk groups for the purpose of treatment differentiation. It should also be remembered that available prognostic factors have been identified only in a retrospective manner, following aggressive treatment of all patients. Thus patients in "favourable" prognostic groups may simply be patients who have had a good effect from aggressive treatment, and how they would have done with reduced treatment remains to be shown. Obviously the best method for prognostication would be the direct demonstration of micrometastatic disease in the lungs or in peripheral blood. In the relatively near future, this may become possible with immunoscintigrapy or immunohistochemistry utilizing monoclonal antibodies [29-31]. In Ewing's sarcoma, the most powerful factors indicating poor prognosis are metastases at diagnosis, poor histologic response, large tumour size and possibly pelvic localisation. There appears to be a somewhat better international consensus regarding prognostic factors in Ewing's sarcoma than in osteosarcoma. Although several studies have implemented intensified treatment for poor prognostic groups [8, 32], the role (if any) of high-dose treatment with stem cell rescue remains to be proven. The same factors are prognostic both for the development of metastases and local recurrence, but in addition, surgical treatment as opposed to radiotherapy appears to reduce local failure rate [12, 17, 33, 34]. As in osteosarcoma, the near future offers promise regarding the detection and quantification of micrometastatses and minimal residual disease, by means of PCR techniques recognizing specific genetic changes in the Ewing family of tumors [35].

C1q-binding substances in peripheral lymph in bronchial carcinoma.

Peripheral leg lymph has been studied for the presence of C1q-binding substances by the I-C1q binding radioassay in six male patients with untreated bronchial carcinoma. In serum, this assay is highly specific for antigen-antibody complexes (immune complexes). Three of the patients had immune complexes in serum, and they all also had C1q-binding substances in peripheral lymph. The C1q-binding activity was quite similar in serum and peripheral lymph. In the other three patients, immune complexes were not found in serum, but in ome of them, moderate amounts of C1q-binding substances were found in peripheral lymph. The results suggest that immune complexes may be found in peripheral lymph in cancer patients in about the same amounts as in serum. However, formal proof is lacking that the C1q-binding substances of peripheral lymph are real immune complexes.

Distribution of methotrexate between plasma and peripheral lymph in man.

The distribution of methotrexate (MTX) to interstitial fluid has been studied by determination of MTX in peripheral lymph from the leg and in plasma after parenteral administration to 6 patients. Peak concentrations of MTX in lymph appear 0.5 to 3.25 h after peak concentrations in plasma. Maximal concentrations in lymph are 16 to 48% lower than in plasma. MTX concentration ratios lymph/plasma were higher than 1.0 (1.0-2.8) in 4 patients, and lower than 1.0 (0.2-0.8) in 2 patients. 12 to 34% of MTX was protein bound in lymph, but the variation in the ratio of bound to free MTX per g lymph protein was only 0.13 to 0.18. The patients with a lymph/plasma MTX ratio above 1.0 will have high and favourable MTX concentrations for distribution to tumours in peripheral tissue, while in the patients with a low ratio conditions for distribution are less favourable. The results indicate that pharmacokinetics of MTX are in accordance with a two or multicompartment model with varying distribution characteristics. The present observations indicate that distribution of MTX is blood flow limited, but the influence of permeability cannot be excluded.

Validation of model-guided placement of external ventricular drains.

PURPOSE: Inaccurate placement of external ventricular drains (EVDs) is a common issue in cerebrospinal diversion procedures. The conventional freehand technique results in a high fraction of sub-optimally placed catheters, and the use of image guidance can improve these results. The purpose of this paper is the validation of the use of an average model for guidance of EVD procedures. METHODS: Three neurosurgeons have tested the model-based technique on three normal volunteers, and we have compared the model-based technique to the freehand technique and neuronavigation based on volunteer-specific images. RESULTS: Our results show that the surgeons perform significantly better when using the model-based technique than when using the freehand technique. CONCLUSIONS: Our results suggest that the use of an average model may improve the accuracy of catheter placements. However, further refinement of the method and testing in a clinical setting is required.