Adjuvant Hyperthermic Intraperitoneal Chemotherapy in Patients With Locally Advanced Colon Cancer (COLOPEC): 5-Year Results of a Randomized Multicenter Trial.

Clinical trials frequently include multiple end points that mature at different times. The initial report, typically based on the primary end point, may be published when key planned co-primary or secondary analyses are not yet available. Clinical Trial Updates provide an opportunity to disseminate additional results from studies, published in JCO or elsewhere, for which the primary end point has already been reported.Whether adjuvant hyperthermic intraperitoneal chemotherapy (HIPEC) might prevent peritoneal metastases after curative surgery for high-risk colon cancer is an ongoing debate. This study aimed to determine 5-year oncologic outcomes of the randomized multicenter COLOPEC trial, which included patients with clinical or pathologic T4N0-2M0 or perforated colon cancer and randomly assigned (1:1) to either adjuvant systemic chemotherapy and HIPEC (n = 100) or adjuvant systemic chemotherapy alone (n = 102). HIPEC was performed using a one-time administration of oxaliplatin (460 mg/m2, 30 minutes, 42°C, concurrent fluorouracil/leucovorin intravenously), either simultaneously (9%) or within 5-8 weeks (91%) after primary tumor resection. Outcomes were analyzed according to the intention-to-treat principle. Long-term data were available of all 202 patients included in the COLOPEC trial, with a median follow-up of 59 months (IQR, 54.5-64.5). No significant difference was found in 5-year overall survival rate between patients assigned to adjuvant HIPEC followed by systemic chemotherapy or only adjuvant systemic chemotherapy (69.6% v 70.9%, log-rank; P = .692). Five-year peritoneal metastases rates were 63.9% and 63.2% (P = .907) and 5-year disease-free survival was 55.7% and 52.3% (log-rank; P = .875), respectively. No differences in quality-of-life outcomes were found. Our findings implicate that adjuvant HIPEC should still be performed in trial setting only.

Evaluation of National Surgical Practice for Lateral Lymph Nodes in Rectal Cancer in an Untrained Setting.

BACKGROUND: Involved lateral lymph nodes (LLNs) have been associated with increased local recurrence (LR) and ipsi-lateral LR (LLR) rates. However, consensus regarding the indication and type of surgical treatment for suspicious LLNs is lacking. This study evaluated the surgical treatment of LLNs in an untrained setting at a national level. METHODS: Patients who underwent additional LLN surgery were selected from a national cross-sectional cohort study regarding patients undergoing rectal cancer surgery in 69 Dutch hospitals in 2016. LLN surgery consisted of either 'node-picking' (the removal of an individual LLN) or 'partial regional node dissection' (PRND; an incomplete resection of the LLN area). For all patients with primarily enlarged (≥7 mm) LLNs, those undergoing rectal surgery with an additional LLN procedure were compared to those  undergoing only rectal resection. RESULTS: Out of 3057 patients, 64 underwent additional LLN surgery, with 4-year LR and LLR rates of 26% and 15%, respectively. Forty-eight patients (75%) had enlarged LLNs, with corresponding recurrence rates of 26% and 19%, respectively. Node-picking (n = 40) resulted in a 20% 4-year LLR, and a 14% LLR after PRND (n = 8; p = 0.677). Multivariable analysis of 158 patients with enlarged LLNs undergoing additional LLN surgery (n = 48) or rectal resection alone (n = 110) showed no significant association of LLN surgery with 4-year LR or LLR, but suggested higher recurrence risks after LLN surgery (LR: hazard ratio [HR] 1.5, 95% confidence interval [CI] 0.7-3.2, p = 0.264; LLR: HR 1.9, 95% CI 0.2-2.5, p = 0.874). CONCLUSION: Evaluation of Dutch practice in 2016 revealed that approximately one-third of patients with primarily enlarged LLNs underwent surgical treatment, mostly consisting of node-picking. Recurrence rates were not significantly affected by LLN surgery, but did suggest worse outcomes. Outcomes of LLN surgery after adequate training requires further research.

Perineal wound closure using gluteal turnover flap or primary closure after abdominoperineal resection for rectal cancer: study protocol of a randomised controlled multicentre trial (BIOPEX-2 study).

BACKGROUND: Abdominoperineal resection (APR) for rectal cancer is associated with high morbidity of the perineal wound, and controversy exists about the optimal closure technique. Primary perineal wound closure is still the standard of care in the Netherlands. Biological mesh closure did not improve wound healing in our previous randomised controlled trial (BIOPEX-study). It is suggested, based on meta-analysis of cohort studies, that filling of the perineal defect with well-vascularised tissue improves perineal wound healing. A gluteal turnover flap seems to be a promising method for this purpose, and with the advantage of not having a donor site scar. The aim of this study is to investigate whether a gluteal turnover flap improves the uncomplicated perineal wound healing after APR for rectal cancer. METHODS: Patients with primary or recurrent rectal cancer who are planned for APR will be considered eligible in this multicentre randomised controlled trial. Exclusion criteria are total exenteration, sacral resection above S4/S5, intersphincteric APR, biological mesh closure of the pelvic floor, collagen disorders, and severe systemic diseases. A total of 160 patients will be randomised between gluteal turnover flap (experimental arm) and primary closure (control arm). The total follow-up duration is 12 months, and outcome assessors and patients will be blinded for type of perineal wound closure. The primary outcome is the percentage of uncomplicated perineal wound healing on day 30, defined as a Southampton wound score of less than two. Secondary outcomes include time to perineal wound closure, incidence of perineal hernia, the number, duration and nature of the complications, re-interventions, quality of life and urogenital function. DISCUSSION: The uncomplicated perineal wound healing rate is expected to increase from 65 to 85% by using the gluteal turnover flap. With proven effectiveness, a quick implementation of this relatively simple surgical technique is expected to take place. TRIAL REGISTRATION: The trial was retrospectively registered at Clinicaltrials.gov NCT04004650 on July 2, 2019.

Long-Term Outcome of Patients with Spinal Dural Arteriovenous Fistula: The Dilemma of Delayed Diagnosis.

BACKGROUND AND PURPOSE: The impact of various radiologic and clinical features on the long-term outcome in spinal dural arteriovenous fistulas is still unclear; thus, they are the purpose of this study. MATERIALS AND METHODS: We retrospectively analyzed our medical data base for all patients treated for spinal dural arteriovenous fistula in our institution between 2006 and 2016. Patient age, neurologic status at the time of diagnosis, the duration of symptoms from onset to diagnosis, and follow-up information were evaluated. The extent of medullary T2WI hyperintensity, intramedullary contrast enhancement, and elongation of perimedullary veins on MR imaging at the time of diagnosis were additionally analyzed. RESULTS: Data for long-term outcome analysis were available in 40 patients with a mean follow-up of 52 months (median, 50.5 months; range, 3-159 months). The mean age at the time of diagnosis was 69.27 ± 9 years (median, 71 years; range, 53-84 years) with a male predominance (n = 32; 80%). The mean duration of symptoms was 20.2 months (median, 10 months; range, 1-120 months). Shorter duration of symptoms at the time of diagnosis was significantly correlated with better outcome of symptoms (P < .05). CONCLUSIONS: Spinal dural arteriovenous fistulas are characterized by interindividually variable clinical presentations, which make a determination of specific predictors for long-term outcome more difficult. Fast and sufficient diagnosis might result in a better outcome after treatment. The diagnosis of spinal dural arteriovenous fistula remains markedly delayed, reflecting an ongoing lack of knowledge and awareness among treating physicians of this rare-but-serious disease.

Treatment strategy and long-term outcome in patients with deep lumbosacral arteriovenous fistulas. A single center analysis in nineteen patients.

OBJECTIVE: Deep lumbosacral dural arteriovenous fistulas (lsDAVF) are rare and present serious diagnostic and treatment difficulties. In our current analysis we present our treatment strategy and the long-term clinical outcome of nineteen patients with lsDAVF. PATIENTS AND METHODS: We retrospectively analyzed our radiological and medical records for patients presenting with SDAVF between 1990 and 2018 at the University Hospital Aachen. We identified twenty patients with a lsDAVF. All patients were treated surgically. One patient died of pulmonary embolism three months after treatment and was excluded from our outcome analysis. Clinical data at time of admission, discharge, one year after discharge and at the last follow-up were evaluated according to modified Aminoff-Logue disability score (AL-score) for this analysis. RESULTS: Mean age was 65 ±â€¯7 years (median, 67; range, 53-78), sixteen patients (84 %) were male. After surgery, four patients developed a recurrent fistula in the same shunt zone and were re-treated microsurgically. Follow-up data one year after treatment was available in 15 patients. No relevant changes in AL-score were observed within this period. For the long-term follow-up analysis, data of 13 patients were available; 38.5 % of patients developed late functional deterioration. CONCLUSION: In our cohort, patients with deep lumbosacral dural arteriovenous fistula had a higher risk of early recurrence compared to patients with thoracolumbar SDAVF, with a considerable percentage of late functional deterioration. Thus strict clinical and radiologic long-term follow-up examinations are recommended in those patients.

Adjuvant hyperthermic intraperitoneal chemotherapy in patients with locally advanced colon cancer (COLOPEC): a multicentre, open-label, randomised trial.

BACKGROUND: Nearly a quarter of patients with locally advanced (T4 stage) or perforated colon cancer are at risk of developing peritoneal metastases, often without curative treatment options. We aimed to determine the efficacy of adjuvant hyperthermic intraperitoneal chemotherapy (HIPEC) in patients with locally advanced colon cancer. METHODS: This multicentre, open-label trial was done in nine hospitals that specialised in HIPEC in the Netherlands. Patients with clinical or pathological T4N0-2M0-stage tumours or perforated colon cancer were randomly assigned (1:1), with a web-based randomisation application, before resection of the primary tumour, to adjuvant HIPEC followed by routine adjuvant systemic chemotherapy (experimental group) or to adjuvant systemic chemotherapy alone (control group). Patients were stratified by tumour characteristic (T4 or perforation), age (<65 years or ≥65 years), and surgical approach of the primary tumour resection (laparoscopic or open). Key eligibility criteria included age between 18 and 75 years, adequate clinical condition for HIPEC, and intention to start adjuvant systemic chemotherapy. Patients with metastatic disease were ineligible. Adjuvant HIPEC consisted of fluorouracil (400 mg/m2) and leucovorin (20 mg/m2) delivered intravenously followed by intraperitoneal delivery of oxaliplatin (460 mg/m2) for 30 min at 42°C, delivered simultaneously or within 5-8 weeks after primary tumour resection. In all patients without evidence of recurrent disease at 18 months, a diagnostic laparoscopy was done. The primary endpoint was peritoneal metastasis free-survival at 18 months, measured in the intention-to-treat population, with the Kaplan-Meier method. Adverse events were assessed in all patients who received assigned treatment. This study is registered with ClinicalTrials.gov, number NCT02231086. FINDINGS: Between April 1, 2015, and Feb 20, 2017, 204 patients were randomly assigned to treatment (102 in each group). In the HIPEC group, two patients withdrew consent after randomisation. In this group, 19 (19%) of 100 patients were diagnosed with peritoneal metastases: nine (47%) during surgical exploration preceding intentional adjuvant HIPEC, eight (42%) during routine follow-up, and two (11%) during diagnostic laparoscopy at 18-months. In the control group, 23 (23%) of 102 patients were diagnosed with peritoneal metastases, of whom seven (30%) were diagnosed by laparoscopy at 18-months and 16 during regular follow-up (therefore making them ineligible for diagnostic laparoscopy). In the intention-to-treat analysis (n=202), there was no difference in peritoneal-free survival at 18-months (80·9% [95% CI 73·3-88·5] for the experimental group vs 76·2% [68·0-84·4] for the control group, log-rank one-sided p=0·28). 12 (14%) of 87 patients who received adjuvant HIPEC developed postoperative complications and one (1%) encapsulating peritoneal sclerosis. INTERPRETATION: In patients with T4 or perforated colon cancer, treatment with adjuvant HIPEC with oxaliplatin did not improve peritoneal metastasis-free survival at 18 months. Routine use of adjuvant HIPEC is not advocated on the basis of this trial. FUNDING: Organization for Health Research and Development and the Dutch Cancer Society.

Submandibular gland botulinum neurotoxin A injection for predicting the outcome of submandibular duct relocation in drooling: a retrospective cohort study.

AIM: This study evaluated whether the effect of submandibular gland botulinum neurotoxin A (BoNT-A) injection can predict the outcome of submandibular duct relocation with sublingual gland excision (SMDR) in children with drooling. Furthermore, we compared the effectiveness of both procedures. METHOD: A retrospective cohort study was performed in 42 children and adolescents (25 males, 17 females; mean [SD] age at BoNT-A injection 11y [4], range 4-20y; mean [SD] age at SMDR 15y [4], range 7-23y) with cerebral palsy or another non-progressive developmental disability who had undergone both BoNT-A injection and SMDR for drooling. Main outcomes were the drooling quotient and the visual analogue scale (VAS) on drooling severity at 8 weeks and 32 weeks follow-up. RESULTS: Failure or success of previous BoNT-A injections had no influence on success of consecutive SMDR. Relative change in main outcomes showed no significant relation between BoNT-A injection and SMDR for any follow-up measurement. After 8 weeks, SMDR was more successful than BoNT-A injection in diminishing VAS (VAS 80.0% vs 54.3%; drooling quotient 56.2% vs 51.0%). After 32 weeks, both drooling quotient (64.3% vs 29.5%) and VAS (75.7% vs 37.1%) showed significantly higher proportions of success for SMDR. INTERPRETATION: The effect of submandibular BoNT-A injection does not predict subsequent SMDR success in drooling. Furthermore, SMDR has a larger and longer-lasting positive effect on drooling than BoNT-A injections. WHAT THIS PAPER ADDS: Submandibular botulinum neurotoxin A (BoNT-A) injection effect does not predict submandibular duct relocation with sublingual gland excision outcome. Submandibular duct relocation is more effective and more permanent than BoNT-A injection.

INYECCIÓN DE NEUROTOXINA BOTULÍNICA A EN LA GLÁNDULA SUBMANDIBULAR PARA PREDECIR EL RESULTADO DE LA REUBICACIÓN DEL CONDUCTO SUBMANDIBULAR EN BABEO: UN ESTUDIO DE COHORTE RETROSPECTIVO: OBJETIVO: Este estudio evaluó si el efecto de la inyección de neurotoxina A botulínica submandibular (BoNT-A) puede predecir el resultado de la reubicación del conducto submandibular con escisión de la glándula sublingual (SMDR) en niños con babeo. Además, comparamos la efectividad de ambos procedimientos. MÉTODO: Se realizó un estudio de cohorte retrospectivo en 42 niños y adolescentes (25 varones, 17 mujeres; edad media [DE] en la inyección de BoNT-A 11 años [4], rango 4-20 años; edad media [SD] a SMDR 15 años [4] rango 7-23 años) con parálisis cerebral u otra discapacidad del desarrollo no progresiva que se haya sometido a una inyección de BoNT-A y SMDR para babear. Los resultados principales fueron el cociente de babeo y la escala analógica visual (VAS) en la severidad del babeo a las 8 semanas y 32 semanas de seguimiento. RESULTADOS: El fracaso o el éxito de las inyecciones anteriores de BoNT-A no tuvo influencia en el éxito de la SMDR consecutiva. El cambio relativo en los resultados principales no mostró una relación significativa entre la inyección de BoNT-A y SMDR para cualquier medición de seguimiento. Después de 8 semanas, SMDR fue más exitoso que la inyección de BoNT-A en la VAS disminuida (VAS 80,0% vs 54,3%; cociente de babeo 56,2% vs 51,0%). Después de 32 semanas, tanto el cociente de babeo (64,3% vs 29,5%) como el VAS (75,7% vs 37,1%) mostraron proporciones significativamente más altas de éxito para SMDR. INTERPRETACIÓN: El efecto de la inyección submandibular de BoNT-A no predice el éxito posterior de SMDR en el babeo. Además, el SMDR tiene un efecto positivo mayor y más duradero en el babeo que las inyecciones de BoNT-A.

INJEÇÃO DE NEUROTOXINA BOTULÍNICA NA GLÂNDULA SUBMANDIBULAR PARA PREDIÇÃO DO RESULTADO DA RELOCACÃO DO DUCTO SUBMANDIBULAR NA SIALORRÉIA: UM ESTUDO DE COORTE RETROSPECTIVO: OBJETIVO: Este estudo avaliou se o efeito da neurotoxina botulínica A (NTBo-A) na glândula submandibular pode predizer o resultado da relocação do ducto submandibular com excisão sublingual da glândula (RDSM) em crianças com sialorréia. Ainda, comparamos a efetividade de ambos os procedimentos. MÉTODO: Um estudo de coorte retrospectivo foi realizado em 42 crianças e adolescentes (25 do sexo masculino, 17 do sexo feminino; idade média [DP] no momento da injeção de NTBo-A 11a[4], variação de 4-20a; idade média [DP] no momento da RDSM 15a [4], variação de 7-23a) com paralisia cerebral ou outra desordem não-progressiva do desenvolvimento que passaram por injeção de NTBo-A e RDSM para sialorréia. Os principais desfechos foram o quociente de sialorréia e a escala visual análoga (EVA) sobre a severidade da sialorréia no acompanhamento de 8 e 32 semanas. RESULTADOS: A falha ou sucesso da NTBo-A prévia não teve influência no sucesso da RDSM consecutiva. A mudança relativa nos principais desfechos não mostrou nenhuma relação significativa entre a injeção de NTBo-A e a RDSM para nenhuma das medidas no acompanhamento. Após 8 semanas, a RDSM foi mais bem sucedida do que a NTBo-A na redução da EVA (EVA 80,0% vs 54,3%; quociente de sialorréia 56,2% vs 51,0%). Após 32 semanas, tanto o quociente de sialorréia (64,3% vs 29,5%) quanto a EVA (75,7% vs 37,1%) mostram proporções significativamente mais altas de sucesso para a RDSM. INTERPRETAÇÃO: O efeito da injeção submandibular de NTBo-A não prediz o sucesso da RDSM subsequente na sialorréia. Ainda, a RDSM tem efeito maior e mais duradouro na sialorréia do que injeções de NTBo-A.

Spinal Epidural Arteriovenous Fistula with Perimedullary Venous Reflux: Clinical and Neuroradiologic Features of an Underestimated Vascular Disorder.

BACKGROUND AND PURPOSE: The purpose of this study was to discuss the clinical and radiologic characteristics of spinal epidural arteriovenous fistulas (SEAVF) and demonstrate their specific angiomorphology in a single-center series. MATERIALS AND METHODS: Thirteen consecutive patients were diagnosed with SEAVF at RWTH Aachen University Hospital between 2006 and 2018 and were included in this study. All patients had MR imaging and DSA before treatment; 10 of these 13 patients received contrast-enhanced MRA (CE-MRA). RESULTS: The mean patient age was 72 ± 8 years. Paraparesis was present in 12 (92%) patients. Sphincter dysfunction and sensory symptoms were observed in 7 (54%) and 6 (46%) patients, respectively. The mean duration of symptoms was 6 ± 8 months. Congestive myelopathy on MR imaging was present in all patients. Prominent arterialized perimedullary veins were demonstrated in only 3 cases. CE-MRA revealed arterialized perimedullary veins and an arterialized epidural pouch in 9/10 (90%) patients, mostly located ventrolaterally. DSA demonstrated a multisegmental extension of the arterialized ventrolateral epidural pouch in 6 (46%) cases. An intradural radicular drainage vein was localized distant from the original fistula point in 3 (23%) patients. CONCLUSIONS: Congestive myelopathy with an acute/subacute clinical course was the dominant finding in spinal epidural arteriovenous fistulas. CE-MRA is a powerful diagnostic tool for identifying arterialized perimedullary veins as well as an arterialized epidural pouch. While arterialized perimedullary veins frequently present with only mild enlargement and elongation in spinal epidural arteriovenous fistulas, the arterialized epidural pouch is frequently located ventrolaterally and may extend over several vertebral levels. DSA remains the criterion standard to precisely visualize a spinal epidural arteriovenous fistula and its intradural radicular drainage vein, which may be located distant from the fistulous point.

Hospital Teaching Status and Patients' Outcomes After Colon Cancer Surgery.

BACKGROUND AND OBJECTIVES: It is increasingly accepted that quality of colon cancer surgery might be secured by combining volume standards with audit implementation. However, debate remains about other structural factors also influencing this quality, such as hospital teaching status. This study evaluates short-term outcomes after colon cancer surgery of patients treated in general, teaching or academic hospitals. METHODS: All patients (n = 23,593) registered in the Dutch Colorectal Audit undergoing colon cancer surgery between 2011 and 2014 were included. Patients were divided into groups based on teaching status of their hospital. Main outcome measures were serious complications, failure to rescue (FTR) and 30-day or in-hospital mortality. Multivariate logistic regression models on these outcome measures and with hospital teaching status as primary determinant were used, adjusted for case-mix, year of surgery and hospital volume. RESULTS: Patients treated in teaching and academic hospitals showed higher adjusted serious complication rates, compared to patients treated in general hospitals (odds ratio 1.25 95% CI [1.11-1.39] and OR 1.23 [1.05-1.46]). However, patients treated in teaching hospitals had lower adjusted FTR rates than patients treated in general hospitals (OR 0.63 [0.44-0.89]). However, for all outcomes there was considerable between-hospitals variation within each type of teaching status. CONCLUSION: On average, patients treated in general hospitals had lower serious complication rates, but patients treated in teaching hospitals had more favorable FTR rates. Given the hospital variation within each hospital teaching type, it is possible to deliver excellent care regardless of the hospital teaching type.

Clinical and Radiologic Characteristics of Deep Lumbosacral Dural Arteriovenous Fistulas.

BACKGROUND AND PURPOSE: Spinal dural arteriovenous fistulas located in the deep lumbosacral region are rare and the most difficult to diagnose among spinal dural arteriovenous fistulas located elsewhere in the spinal dura. Specific clinical and radiologic features of these fistulas are still inadequately reported and are the subject of this study. MATERIALS AND METHODS: We retrospectively evaluated all data of patients with spinal dural arteriovenous fistulas treated and/or diagnosed in our institution between 1990 and 2017. Twenty patients with deep lumbosacral spinal dural arteriovenous fistulas were included in this study. RESULTS: The most common neurologic findings at the time of admission were paraparesis (85%), sphincter dysfunction (70%), and sensory disturbances (20%). Medullary T2 hyperintensity and contrast enhancement were present in most cases. The filum vein and/or lumbar veins were dilated in 19/20 (95%) patients. Time-resolved contrast-enhanced dynamic MRA indicated a spinal dural arteriovenous fistula at or below the L5 vertebral level in 7/8 (88%) patients who received time-resolved contrast-enhanced dynamic MRA before DSA. A bilateral arterial supply of the fistula was detected via DSA in 5 (25%) patients. CONCLUSIONS: Clinical symptoms caused by deep lumbosacral spinal dural arteriovenous fistulas are comparable with those of spinal dural arteriovenous fistulas at other locations. Medullary congestion in association with an enlargement of the filum vein or other lumbar radicular veins is a characteristic finding in these patients. Spinal time-resolved contrast-enhanced dynamic MRA facilitates the detection of the drainage vein and helps to localize deep lumbosacral-located fistulas with a high sensitivity before DSA. Definite detection of these fistulas remains challenging and requires sufficient visualization of the fistula-supplying arteries and draining veins by conventional spinal angiography.

Blunted serum and enhanced salivary free cortisol concentrations in the chronic phase after aneurysmal subarachnoid haemorrhage--is stress the culprit?

Spontaneous aneurysmal subarachnoid haemorrhage (SAH) is a cause of stroke, which constitutes a severe trauma to the brain and may lead to serious long-term medical, psychosocial and endocrinological sequelae. Adrenocorticotrophic hormone deficiency, which is considered to occur in up to 20% of all survivors, is a possible consequence of bleeding. Moreover, preliminary data suggest that a poor psychosocial outcome in SAH survivors is linked to alterations in cortisol secretion. Despite these findings, investigation of diurnal cortisol profiles and the cortisol awakening response (CAR) in chronic SAH patients has not been done so far. In this study, basal serum cortisol and salivary cortisol concentration profiles were investigated in 31 SAH patients more than 1 year after the acute event and in 25 healthy controls. Additionally, low-dose dexamethasone (DEX) suppression tests were conducted, and sensitivity to stress was measured with a psychometric questionnaire (Neuropattern(TM)). Although significantly higher salivary cortisol concentrations were observed on waking in SAH patients (p = 0.013, ANOVA), without a CAR change, total serum cortisol concentrations were blunted, but only in patients with high levels of perceived stress (SAH high stress: 337 nmol/l, SAH low stress: 442 nmol/l, controls: 467 nmol/l; Controls vs. SAH high stress p = 0.018). DEX suppression of cortisol secretion was not significantly different between patients and controls. The results indicate that total (serum) and free (salivary) cortisol concentrations give different information about cortisol availability in patients after aneurysmal SAH. Enhanced free cortisol concentrations may reflect a meaningful biological coping mechanism in SAH patients.

Bare, bio-active and hydrogel-coated coils for endovascular treatment of experimentally induced aneurysms. Long-term histological and scanning electron microscopy results.

Endovascular treatments of cerebral aneurysms with bare platinum coils have a higher rate of recurrence compared to surgical clipping. This may be related to failed vessel wall reconstruction since histological and scanning electron microscopy results following embolization failed to demonstrate neoendothelialization over the aneurysm neck. The present study tried to elucidate whether the use of modified coils resulted in a better rate of reconstructing the vessel wall over the aneurysm neck in experimental aneurysms. Aneurysms were created in 20 rabbits by intraluminal elastase incubation of the common carotid artery. Five animals each were assigned to the following groups: untreated, bare platinum coils, bioactive coils with polyglycolic/polylactic acid coating, and hydrogel-coated platinum coils. After 12 months, angiography, histology and scanning electron microscopy was performed. No neoendothelial layer was visualized in the bioactive and bare coil groups with a tendency to an increased layering of fibroblasts along the bioactive coils at the aneurysm fundus. However, at the aneurysm neck perfused clefts were present and although a thin fibrinous layer was present over some coils, no bridging neointimal or neoendothial layer was noted over different coils. Following loose Hydrogel coiling, a complete obliteration of the aneurysm was present with neoendothelialization present over different coil loops. The study demonstrates that with surface coil modifications complete and stable aneurysm obliteration may become possible. A smooth and dense surface over the aneurysm neck may be necessary for endothelial cells to bridge the aneurysm neck and to lead to vessel wall reconstruction.

Subarachnoid hemorrhage following posterior spinal artery aneurysm. A case report and review of the literature.

Isolated posterior spinal artery aneurysms are rare vascular lesions. We describe the case of a 43-year-old man presenting with spinal subarachnoid hemorrhage after a minor trauma who was found to have a dissecting aneurysm of a posterior spinal artery originating from the right T4 level. Endovascular treatment was not contemplated because of the small size of the feeding artery, whereas surgical resection was deemed more appropriate because of the posterolateral perimedullary location that was well appreciated on CT angiography. After surgical resection of the aneurysm the patient had a complete neurological recovery. In comparison to anterior spinal artery aneurysms whose pathogenesis is diverse, posterior spinal aneurysms are most often secondary to a dissection and represent false or spurious aneurysms. Although the definite diagnosis still requires spinal angiography, MRI and CT may better delineate the relationship of the aneurysm to the spinal cord in order to determine the best treatment method. Prompt treatment is recommended as they have high rebleeding and mortality rates.

Intramedullary hemangioblastomas: timing of surgery, microsurgical technique and follow-up in 23 patients.

Hemangioblastomas are highly vascularised tumors of the central nervous system and account for 1.5-2.5% of all spinal cord tumors. Because of the rarity of these tumors, surgical experience is often limited and, therefore, treatment and indications for timing of surgery are discussed controversial. The authors reviewed their data of 23 consecutive patients with respect to timing of surgery, microsurgical technique, and follow-up. Clinical records of 23 consecutive patients with intramedullary hemangioblastomas who underwent first surgery in our department between 1990 and 2005 were reviewed. In three cases the tumors were localised at the craniocervical junction; four patients had a single tumor in the cervical spine, six patients multiple tumors in the cervical and thoracic spine, eight patients in the thoracic spine only, one patient in the conus region, and one patient had multiple tumors located in the thoracic and lumbar spine. In eight patients, a von-Hippel-Lindau disease (VHL) was associated. The neurological follow-up was evaluated according to the classification of McCormick. Operation was recommended to every symptomatic patient as early as possible. In asymptomatic patients with a sporadic tumor surgery was discussed for diagnostic purposes at any time. In VHL patients, surgery was recommended if tumor growth was observed on MRI in the next practicable time. All tumors were diagnosed by magnetic resonance imaging and in all cases but one a DSA was performed. All patients were treated microsurgically through a posterior approach. The tumors in the spinal cord were removed microsurgically through a partial hemilaminectomy (n = 1), a hemilaminectomy (n = 15), or laminectomy (n = 4) and at the craniocervical junction (n = 3) through a suboccipital craniotomy. During follow-up after 6 months, 18 patients remained neurologically stable (17 in McCormick grade I and 1 in McCormick grade II) and 5 patients recovered to a better status (3 from grade III to II, 2 from grade II to I). There was one complication with a CSF fistula and one recurrence/incomplete removal. Following the above-mentioned principles of microsurgical removal of intramedullary hemangioblastomas, operation is possible with a low procedure-related morbidity and can be recommended especially in VHL patients with progressive symptoms or tumor growth during follow-up. Patients without VHL most frequently require hemangioblastoma resection for diagnostic purposes and/or because symptoms prompted an imaging work-up that lead to the discovery of the tumor.

A less invasive surgical concept for the resection of spinal meningiomas.

BACKGROUND: The surgical strategy for spinal meningiomas usually consists of laminectomy, initial tumour debulking, identification of the interface between tumour and spinal cord, resection of the dura including the matrix of the tumour, and duroplasty. The objective of this study was to investigate whether a less invasive surgical strategy consisting of hemilaminectomy or laminectomy, tumour removal and coagulation of the tumour matrix allows comparable surgical and clinical results to be obtained, especially without an increase of the recurrence rate as reported in the literature. PATIENTS AND METHODS: Between 1990 and 2005, 61 patients (11 men, 50 women) underwent surgery for spinal meningioma. All patients were treated microsurgically by a posterior approach. In 56 of the 61 patients, the above outlined - less invasive - surgical technique with tumour removal and coagulation of the tumour matrix was performed. In 5 patients, dura resection and duroplasty was additionally performed. Electrophysiological monitoring was routinely used since 1996. Recurrence was defined as new onset or worsening of symptoms and radiological confirmation of tumour growth. The pre-and post-operative clinical status was measured by the Frankel grading system. RESULTS: Pre-operatively, 40 patients were in Frankel grade D, 13 patients in grade C, 6 patients in grade E and 1 patient each in grade A and B. Following surgery no patient presented a permanent worsening of clinical symptoms. All patients who initially presented with a Frankel grades A-C (n = 15) recovered to a better grade at the time of follow-up. Patients who presented with Frankel grade D remained in stable condition (n = 27) or recovered to a better neurological status (n = 13). Two patients experienced a temporary worsening of their symptoms, but subsequently improved to a better state than pre-operatively. Two (3.3%) complications (pseudomeningocele, wound infection) requiring surgery, were encountered. The pseudomeningocele developed in a patient who underwent durotomy. During the follow-up period of 2 months to 10 years (mean 31.3 months), 3 patients (5%) required surgery for symptomatic recurrence: 1 patient had 2 recurrences that occurred 4 and 7 years after first tumour removal and matrix coagulation, 1 recurrence occurred 1 year after tumour removal that was accompanied by matrix coagulation in a patient with a diffuse anterocranial tumour extension and 1 occurred 3 years after tumour removal and durotomy. Two patients showed a small recurrence on MRI during follow-up after 2 and 5 years, respectively, without any symptoms requiring surgery. CONCLUSIONS: The high rate of favourable clinical results combined with the low rate of recurrences supports our less invasive surgical concept, which does not aim for resection of the dural matrix of the spinal meningioma.

The aneurysmal wall. The key to a subclassification of intracranial arterial aneurysm vasculopathies?

SUMMARY: The pathogenesis of intracranial arterial aneurysms (AA) has been debated for many years and still remains unclear, although these entities might pose life-threatening risks to the patient and understanding the disease is of utmost importance for choosing treatment concepts. Apart from the "classical" berry-type aneurysm, there are different other types of intracranial AA such as infectious, dissecting or giant, partially thrombosed aneurysms. From the clinician's perspective, the hypothesis that some of these intracranial aneurysms might be due to abluminal factors has been put forward for many years. Alterations of the vessel wall, either due to luminal or abluminal factors may be employed for an etiological classification of aneurysmal vasculopathies as will be discussed in this article. Moreover, regarding certain aneurysmal vasculopathies as an abluminal disease might alter current therapeutic strategies since therapy should not only aim at the intraluminal repair of the artery but may also target the vessel wall.

Spinal vascular malformations--typical and atypical findings.

Vascular malformations of the spinal cord and its meninges are rare diseases which comprise true inborn cavernomas and arteriovenous malformations (AVM), including perimedullary fistulae, glomerular and juvenile AVMs, and presumably acquired dural arteriovenous fistulae. This article gives an overview of the imaging features on magnetic resonance imaging (MRI) and digital subtraction angiography of both typical and atypical findings to describe the wide variety of possible pathological entities encountered. Clinical differential diagnoses, the neurological symptomatology and potential therapeutic approaches of these diseases, which may vary depending on the underlying pathology, are given. Although MRI constitutes the first choice diagnostic modality for suspected spinal vascular malformations, we conclude that the definite diagnosis of the disease and thus the choice of the appropriate therapeutic approach rests on selective spinal angiography which should be performed at a specialized center. Treatment in symptomatic patients offers an improvement in prognosis. Microsurgical treatment is recommended for symptomatic spinal cord cavernomas. Dural arteriovenous shunts can either be treated by microsurgical or endovascular approaches, the former being a simple, quick and secure approach to obliterate the fistula while the latter is technically demanding. In spinal arteriovenous malformations of both the fistulous and the glomerular type, the endovascular approach is the method of first choice; in selected cases, surgery or a combined therapy may be necessary.

Magnetic versus manual guidewire manipulation in neuroradiology: in vitro results.

INTRODUCTION: Standard microguidewires used in interventional neuroradiology have a predefined shape of the tip that cannot be changed while the guidewire is in the vessel. We evaluated a novel magnetic navigation system (MNS) that generates a magnetic field to control the deflection of a microguidewire that can be used to reshape the guidewire tip in vivo without removing the wire from the body, thereby potentially facilitating navigation along tortuous paths or multiple acute curves. METHOD: The MNS consists of two permanent magnets positioned on either side of the fluoroscopy table that create a constant precisely controlled magnetic field in the defined region of interest. This field enables omnidirectional rotation of a 0.014-inch magnetic microguidewire (MG). Speed of navigation, accuracy in a tortuous vessel anatomy and the potential for navigating into in vitro aneurysms were tested by four investigators with differing experience in neurointervention and compared to navigation with a standard, manually controlled microguidewire (SG). RESULTS: Navigation using MG was faster (P=0.0056) and more accurate (0.2 mistakes per trial vs. 2.6 mistakes per trial) only in less-experienced investigators. There were no statistically significant differences between the MG and the SG in the hands of experienced investigators. One aneurysm with an acute angulation from the carrier vessel could be navigated only with the MG while the SG failed, even after multiple reshaping manoeuvres. CONCLUSION: Our findings suggest that magnetic navigation seems to be easier, more accurate and faster in the hands of less-experienced investigators. We consider that the features of the MNS may improve the efficacy and safety of challenging neurointerventional procedures.