Recommendations for the referral of patients for proton-beam therapy, an Alberta Health Services report: a model for Canada?

BACKGROUND: Compared with photon therapy, proton-beam therapy (pbt) offers compelling advantages in physical dose distribution. Worldwide, gantry-based proton facilities are increasing in number, but no such facilities exist in Canada. To access pbt, Canadian patients must travel abroad for treatment at high cost. In the face of limited access, this report seeks to provide recommendations for the selection of patients most likely to benefit from pbt and suggests an out-of-country referral process. METHODS: The medline, embase, PubMed, and Cochrane databases were systematically searched for studies published between January 1990 and May 2014 that evaluated clinical outcomes after pbt. A draft report developed through a review of evidence was externally reviewed and then approved by the Alberta Health Services Cancer Care Proton Therapy Guidelines steering committee. RESULTS: Proton therapy is often used to treat tumours close to radiosensitive tissues and to treat children at risk of developing significant late effects of radiation therapy (rt). In uncontrolled and retrospective studies, local control rates with pbt appear similar to, or in some cases higher than, photon rt. Randomized trials comparing equivalent doses of pbt and photon rt are not available. SUMMARY: Referral for pbt is recommended for patients who are being treated with curative intent and with an expectation for long-term survival, and who are able and willing to travel abroad to a proton facility. Commonly accepted indications for referral include chordoma and chondrosarcoma, intraocular melanoma, and solid tumours in children and adolescents who have the greatest risk for long-term sequelae. Current data do not provide sufficient evidence to recommend routine referral of patients with most head-and-neck, breast, lung, gastrointestinal tract, and pelvic cancers, including prostate cancer. It is recommended that all referrals be considered by a multidisciplinary team to select appropriate cases.

Pediatric temporal lobectomy for epilepsy.

BACKGROUND: Temporal lobectomy in adults is an accepted form of treatment for patients with intractable complex partial seizures. There have been few long-term studies of children undergoing temporal lobectomy for epilepsy. METHODS: We reviewed the pediatric cases of temporal lobectomy for intractable epilepsy performed by the Comprehensive Epilepsy Program at the University of Alberta Hospitals between 1988 and 2000. All patients had preoperative and postoperative clinical evaluations, seizure charts, drug levels, EEG, CT/MRI, long-term video EEG monitoring and neuropsychological testing. The patients were reassessed at 6 weeks, 6 months and 1 year postoperatively, then yearly. The duration of follow up was 1-10 years (mean 5 years). RESULTS: Forty-two patients were studied (25 males and 17 females). Age at surgery ranged from 18 months to 16 years. The interictal EEG was abnormal in 38 of the 42 patients. Twenty-two patients had focal epileptic discharge and 1 had generalized epileptic discharge. Focal slowing was seen in 9 patients and diffuse slowing in 5 patients. CT scan was abnormal in 17 of 39 patients and normal in 22 of 39. MRI was abnormal in 34 of 42 patients and normal in 8 of 42. Pathology included brain tumors in 14 patients, mesial temporal sclerosis in 8, focal cortical dysplasia in 4, tuberous sclerosis in 4, dual pathology in 4, porencephalic cyst in 1 and normal pathology or gliosis in 6. Thirty-three of 42 patients (78%) were seizure-free following surgery and an additional 5 (12%) had a decrease in seizure frequency. Three patients had complications, but there were no deaths. CONCLUSION: Temporal lobectomy is a safe and effective treatment for children with intractable complex partial seizures. Seventy-eight percent of patients are seizure-free following the surgery and there are few complications. MRI is superior to CT scan for detection of temporal lobe pathology yet failed to detect abnormalities in some patients. The most common pathologies found were brain tumors, mesial temporal sclerosis and developmental lesions. In addition to seizure control, many patients experienced improvement in cognitive and psychosocial function following surgery.

Resection of the lesion in patients with hypothalamic hamartomas and catastrophic epilepsy.

BACKGROUND: Patients with hypothalamic hamartomas (HH) often have severe refractory epilepsy, incapacitating behavioral abnormalities, and cognitive decline. Attempts to control the seizure disorder by resection of apparently epileptogenic mesial temporal or other cortical structures have failed consistently. OBJECTIVE: To report a series of 13 patients in whom the hamartoma itself was resected. METHODS: All patients underwent preoperative evaluation between ages 2 and 33 years and had subtotal or complete resection of the hamartoma. Follow-up ranged from 1 to 5.5 years (mean: 2.8 y). RESULTS: Preoperatively, all patients had variable combinations of gelastic, complex partial, and generalized seizures. Eight had drop attacks. In addition, all had marked behavior abnormalities and cognitive impairment. Postoperatively, two patients are completely seizure-free and 11 are either seizure-free or have achieved a greater than 90% reduction of drop attacks and generalized tonic-clonic seizures. However, minor gelastic, complex partial, and atypical absence seizures have persisted in 11 patients, although at significantly reduced rates. In addition, there has been a dramatic improvement in behavior and cognition. Three patients had an anterior thalamic and one a capsular infarct, which left only minimal long-term deficits. Exact location of the lesion in relation to the interpeduncular fossa and the walls of the third ventricle correlated with extent of excision, seizure control, and complication rate. CONCLUSION: Resection can alleviate both the seizures and the behavioral and cognitive abnormalities of hypothalamic hamartomas, but complications are frequent.

Pathology and neuroimaging in pediatric temporal lobectomy for intractable epilepsy.

OBJECTIVES: Firstly, to study the pathology at surgery in children undergoing temporal lobectomy for intractable partial epilepsy. Secondly, to compare neuroimaging techniques (CT, MRI) in the preoperative detection of pathology. Lastly, to examine the surgical outcome in children. METHODS: Forty-two pediatric patients undergoing temporal lobectomy for intractable epilepsy at the Comprehensive Epilepsy Program at the University of Alberta Hospital between the years 1988-1998 were studied. Patients had extensive preoperative investigations including CT and MRI. The pathology at surgery was reviewed and compared to preoperative neuroimaging. Charts were reviewed to determine surgical outcome. RESULTS: Brain tumors were the most common pathology, found in 13/42 patients. Mesial temporal sclerosis (MTS) was found in 8 patients and dual pathology in an additional 5. Focal cortical dysplasia (FCD) was seen in 4 patients, 1 patient had a porencephalic cyst and 4 patients had tubers of tuberous sclerosis. Seven patients had no specific pathology detected. MRI was clearly more sensitive than CT in the detection of pathology. MRI was abnormal in 27/42 cases (64%), while CT scan was found to be abnormal in only 12/39 (31%). Surgical outcome was excellent, with 34/42 patients (80%) having an Engel class I outcome. One patient had significant improvement with an Engel class II outcome, 3 (7%) had little improvement (Engel class III) and 4 (10%) were unchanged (Engel class IV). Three patients (7%) had surgical complications. CONCLUSIONS: A wide variety of developmental pathology is seen following temporal lobectomy for intractable epilepsy of childhood. Brain tumors, FCD and MTS are common. MRI is superior to CT in the detection of pathology, which may be subtle in children. Surgical outcome is excellent, with most children being seizure free and few complications being seen.

A modified lateral decubitus position for surgical approaches to midline posterior fossa lesions: technical note.

Although a number of operative positions have been described for approaching midline posterior fossa tumors, all have potential disadvantages and complications. We describe a modified lateral decubitus position for the removal of posterior fossa tumors. The position allows blood and cerebrospinal fluid to drain from the operative wound and provides a straight-on view of the posterior fossa contents. It also allows the surgeon to sit comfortably during tumor removal, thereby reducing operator fatigue. We have found this to be a reliable and valuable approach for posterior fossa pathology.

Anatomic details of intradural channels in the parasagittal dura: a possible pathway for flow of cerebrospinal fluid.

OBJECTIVE: The absorption of cerebrospinal fluid occurs primarily by means of arachnoid granulations (AG) in the superior sagittal sinus (SSS) and the lacunae laterales (LL) in the parasagittal dura. Previous descriptions of this region suggest a network of intradural channels, but finer details of extent and relationship between channels and AG were not addressed. Therefore, we undertook an anatomic study of cadaveric parasagittal dura. METHODS: The SSS and parasagittal dura of 20 formalin-fixed adult cadavers and 15 autopsy specimens from patients ranging in age from 18 weeks of gestation to 80 years were studied by use of a light microscope, a scanning electron microscope, and corrosion casting. Intradural injections into the parasagittal region were performed in two formalin-fixed and four autopsy specimens from adults by use of normal saline and corrosion casting. RESULTS: Extensive networks of intradural channels from 0.02 to 2.0 mm in diameter were noted in all of the specimens. Channels either were connected to the SSS at intervals along the side wall or drained directly into the LL, which extended up to 3 cm from midline. Channels lined with endothelium stained positive for Factor VIII, as did the endothelium of the LL and SSS. In some places, the network of channels seemed to coalesce to form LL. The underside of the dura was coarse and trabeculated where the channels were abundant, and AG were interdigitated between these trabeculae. In regions of the dura where channels were sparse or absent, the dural underside was smooth and lacked AG. Underlying cortical veins opened directly into the SSS and were unrelated to intradural channels. Intradural parasagittal injections from the epidural side accessed the SSS by way of channels using pressures between 0 and 20 cm H2O at 1.5 ml/min. CONCLUSION: These channels may represent a pathway for the flow of cerebrospinal fluid from AG to the SSS.

Sickle cell trait and stroke in children.

Cerebrovascular complications of sickle cell anemia are well known to be one of the more common causes of stroke in the pediatric age group. Although it is far less common, the association of stroke with sickle cell trait has been described in young adults and only twice in children in the English literature. In this report, we describe a case of a posterior circulation infarct occurring in a 12-year-old male who also had a normal variant vertebral artery, which may have been a contributing factor in his presentation. The literature is reviewed and other possible risk factors for stroke in sickle cell trait are discussed.

The history and classification of hydrocephalus.

Although great strides have been made toward understanding and managing hydrocephalus, the problem has not been solved completely. This article offers a discussion of hydrocephalus according to historical perspectives, various surgical techniques, including ventriculoatrial and ventriculoperitoneal silicone shunt systems, and classification schemes.

An approach to the management of arrested and compensated hydrocephalus.

Arrested hydrocephalus is defined as adequately shunted hydrocephalus while all other forms of hydrocephalus are at various levels of compensation. Compensation occurs at some cost to the child. Weighing the cost of compensation versus the risk of a shunt is used to decide which course to follow. Close observation with objective data is mandatory if the decision is made not to shunt the young child. In the very young, less than 3 years of age, one should probably err on the side of inserting a shunt.

Management of the child with severe brain injury.

The pathophysiology and clinical management of acute brain injury in infancy and childhood are presented using acute traumatic brain injury as a model. The principles of stabilization, transport, and intensive care management are critically reviewed.

The effects of labor and delivery on spinal cord function and ambulation in patients with meningomyelocele.

Two hundred and eight patients with meningomyeloceles were reviewed to assess the role of birth trauma in the pathogenesis of their neurological deficit. Vaginal breech-delivered patients appeared to have poorer neurological function in the newborn period. The factors responsible include: (1) a mid or upper lumbar level, that by sparing hip flexors and knee extensors, predisposes to breech presentation; (2) limb posturing due to residual neurological function and intrauterine positioning that limits the accurate neurological assessment of the newborn; (3) nervous system or soft tissue injury due to labor and delivery. Regardless of the mechanism, vaginal breech-delivered patients showed improvement in function, and eventually exhibited ambulatory function comparable to those infants born by cesarian section or vaginally after vertex presentation and labor. In our patient population, elective cesarian section did not offer a spinal cord or ambulatory advantage over vaginal delivery for those pregnancies presenting in a vertex fashion. Thus, it should be reserved for fetuses who are presenting breech or who have other obstetrical indications for operative delivery.

Glutathione levels and chemosensitizing effects of buthionine sulfoximine in human malignant glioma cells.

Biopsy samples and cultured cells derived from them were obtained from 39 patients with malignant glioma and were analyzed for 1) glutathione (GSH) content; 2) sensitivity to 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU) and/or nitrogen mustard (HN2) treatment and 3) the effect of buthionine sulfoximine (BSO) treatment on BCNU and/or HN2 cytotoxicity. The average GSH concentration of biopsy specimens was lower than those of cultured cells (2.36 +/- 0.44 vs. 11.42 +/- 2.32 nmol/10(6) cells). While some of the tumor specimens were sensitive to either BCNU or HN2, the majority were resistant to both. However, 8 of 23 tumors tested showed enhanced sensitivity to BCNU following treatment with BSO. Five of 17 tumors were similarly sensitized to HN2 by BSO. These results suggest that BSO chemosensitization may be of value for certain patients and that screening assays may help identify treatment-sensitive individuals.

Absence of IFNA and IFNB genes from human malignant glioma cell lines and lack of correlation with cellular sensitivity to interferons.

We report that 5 of 19 human malignant glioma cell lines have neither interferon alpha (IFNA) nor interferon beta (IFNB) genes that are detectable by Southern blotting. Of 5 other of these malignant glioma lines that have a single IFNB gene copy, 3 lack the IFNA genes entirely and two have one copy. One of the lines that lacks the IFNA genes entirely but has one copy of the IFNB gene has a rearrangement near the IFNB gene that is most easily interpreted as an insertion of a large segment of DNA (at least 50 kilobases) the 3' end of which is less than 1.3 kilobases 5' to the known regulatory sequences of the IFNB gene. In spite of the rearrangement, IFNB-specific RNA is highly inducible in this line by poly(I)-poly(C). The ability of interferon alpha or interferon beta to inhibit cell growth does not depend upon the presence or absence of the respective gene. This finding adds solid tumors to those tumor cell lines (acute lymphocytic leukemia, chronic myelogeneous leukemia) previously determined to lack the IFNA and IFNB genes (Diaz et al., Proc. Natl. Acad. Sci. USA, 85:5259-5263, 1988).

Management and postoperative mortality related to time of clipping for supratentorial aneurysms: a personal series.

An analysis of all 197 consecutive cases of intracranial aneurysms treated by one of us (B. W.) was carried out. 82% were ruptured anterior circle aneurysms. 144 cases were analyzed with respect to post-operative and management mortality where patients were eligible for definitive clipping. Grade-time interactions on transfer to the neurosurgeon were considered. Early operation was not associated with significantly higher post-operative and management mortality. 116 cases clipped and discharged from hospital had longer follow-ups to see if earlier operation was associated with a poorer neurological and social outcome. This was not the case. We therefore believe that since the prime rationale for surgery following subarachnoid haemorrhage is the prevention of rebleeding and since this is more common immediately following the initial haemorrhage, early surgery is indicated whenever this is technically feasible. Since 1978, with a deliberate policy of trying to operate early, for all grades there has been a post-operative mortality of 3%, a case management mortality of 20% and 87% of patients operated upon have been able to go home.

Management mortality and the timing of surgery for supratentorial aneurysm.

A retrospective analysis of 224 patients with a ruptured supratentorial aneurysm, admitted to the care of one of six neurosurgeons on the day or or the day following their subarachnoid hemorrhage, was carried out. Both postoperative and management mortality rates were calculated by the grade of the patient on admission. There were no statistically significant differences in postoperative and management mortality rates when patients were categorized by time of operation, except for the increased management mortality for Grade 3 and 4 patients who were operated on late.