François Porchet

Promising Survival for Patients With Newly Diagnosed Glioblastoma Multiforme Treated With Concomitant Radiation Plus Temozolomide Followed by Adjuvant Temozolomide

PURPOSE Temozolomide is a novel oral alkylating agent with demonstrated efficacy as second-line therapy for patients with recurrent anaplastic astrocytoma and glioblastoma multiforme (GBM). This phase II study was performed to determine the safety, tolerability, and efficacy of concomitant radiation plus temozolomide therapy followed by adjuvant temozolomide therapy in patients with newly diagnosed GBM. PATIENTS AND METHODS Sixty-four patients were enrolled onto this open-label, phase II trial. Temozolomide (75 mg/m(2)/d x 7 d/wk for 6 weeks) was administered orally concomitant with fractionated radiotherapy (60 Gy total dose: 2 Gy x 5 d/wk for 6 weeks) followed by temozolomide monotherapy (200 mg/m(2)/d x 5 days, every 28 days for six cycles). The primary end points were safety and tolerability, and the secondary end point was overall survival. RESULTS Concomitant radiation plus temozolomide therapy was safe and well tolerated. Nonhematologic toxicities were rare and mild to moderate in severity. During the concomitant treatment phase, grade 3 or 4 neutropenia, thrombocytopenia, or both were observed in 6% of patients, including two severe infections with Pneumocystis carinii. During adjuvant temozolomide, 2% and 6% of cycles were associated with grade 3 and 4 neutropenia or thrombocytopenia, respectively. Median survival was 16 months, and the 1- and 2-year survival rates were 58% and 31%, respectively. Patients younger than 50 years old and patients who underwent debulking surgery had the best survival outcome. CONCLUSION Continuous daily temozolomide and concomitant radiation is safe. This regimen of concomitant chemoradiotherapy followed by adjuvant chemotherapy may prolong the survival of patients with glioblastoma. Further investigation is warranted, and a randomized trial is ongoing.

Great expectations: really the novel predictor of outcome after spinal surgery?

Study Design. Prospective study. Objective. The present study compared different theories on the role of expectations in a group of patients undergoing lumbar decompression surgery. Summary of Background Data. Patients’ expectations of treatment are a potentially important predictor of self-rated outcome after surgery. Some studies suggest that high baseline expectations per se yield better outcomes, others maintain that the fulfillment of prior expectations is paramount, and still others assert that it is the actual improvement in symptom status that governs outcome, regardless of prior expectations. Methods. Hundred patients took part (33 F, 67 M; mean [SD] age, 65 [11] yrs). Before surgery, they completed a booklet containing the Roland-Morris (RM) disability questionnaire, 0–10 pain graphic rating scales (back and leg separately), and Likert-scales about the degree of improvement expected in various domains. Two and 12 months after surgery, questions were answered regarding the perceived improvement for each of these domains, the RM and pain scales were completed again, and the patients rated the global outcome on a 5-point Likert-scale. Results. Compared with the actual improvement recorded at 12 months, prior expectations had been overly optimistic in about 40% patients for the domains leg pain, back pain, walking capacity, social life, mental well-being, and independence, and in 50% patients for everyday activities and sport. There was no significant relationship between baseline expectations and follow-up scores for back pain, leg pain, RM-disability (corrected for baseline values), or global outcome. Hierarchical multiple regression analysis revealed that “expectations being fulfilled” was the most significant predictor of global outcome. Conclusion. In this patient group, expectations of surgery were overly optimistic. Having one’s expectations fulfilled was most important for a good outcome. The results emphasize the importance of assessing patient-orientated outcome in routine practice, and the factors that might influence it, such that realistic expectations can be established for patients before surgery.

Cytochrome P-450 activities in human and rat brain microsomes

The role of cytochrome P450 in the metabolism of dextromethorphan, amitriptyline, midazolam, S-mephenytoin, citalopram, fluoxetine and sertraline was investigated in rat and human brain microsomes. Depending on the parameters, the limit of quantification using gas chromatography-mass spectrometry methods was between 1.6 and 20 pmol per incubation, which generally contained 1500 microg protein. Amitriptyline was shown to be demethylated to nortriptyline by both rat and human microsomes. Inhibition studies using ketoconazole, furafylline, sulfaphenazole, omeprazole and quinidine suggested that CYP3A4 is the isoform responsible for this reaction whereas CYP1A2, CYP2C9, CYP2C19 and CYP2D6 do not seem to be involved. This result was confirmed by using a monoclonal antibody against CYP3A4. Dextromethorphan was metabolized to dextrorphan in rat brain microsomes and was inhibited by quinidine and by a polyclonal antibody against CYP2D6. Only the addition of exogenous reductase allowed the measurement of this activity in human brain microsomes. Metabolites of the other substrates could not be detected, possibly due to an insufficiently sensitive method. It is concluded that cytochrome P450 activity in the brain is very low, but that psychotropic drugs could undergo a local cerebral metabolism which could have pharmacological and/or toxicological consequences.

Early surgery for brainstem cavernomas

SummaryBackground. The purpose was to review our experience with the surgical management of brainstem cavernomas (BSCs) and especially the impact of the surgical timing on the clinical outcome.Method. We retrospectively reviewed 22 patients harboring a BSC, who underwent 23 procedures.Findings. Surgery was carried out during the early stage after the last haemorrhage, with a mean delay of 21.6 days (range 4–90 days). Sixteen procedures were performed after a first bleeding event while seven after multiple bleedings. Complete resection was achieved in 19 patients (86.4%). Early after surgery, 12 patients (52.2%) improved neurologically, 5 (21.7%) were stable and 6 (26.1%) worsened. New postoperative deficits were noted after 9 procedures (39.1%). Statistically significant factors for postoperative aggravation were: late surgery (P = 0.046) and multiple bleedings (P = 0.043). No patient operated on within the first 19 days after bleeding did worsen (n = 11), as opposed to 6 out of 12 who did when operated on later. After a mean follow-up of 44.9 months, 20 patients (90.9%) were improved, 1 patient (4.6%) was worse and 1 patient was lost to follow-up (4.6%), after reoperation for rebleeding of a previously completely resected cavernoma. Late morbidity was reduced to 8.6%. The mean Glasgow Outcome Scale (GOS) at the end of the follow-up period was 4.24, compared to a mean preoperative GOS of 3.22 (P<0.001). Complete neurological recovery of motor deficits, sensory disturbances, cranial nerves (CNs), internuclear ophtalmoplegia and cerebellar dysfunction were respectively 41.7%, 38.5%, 52.6%, 60.0% and 58.3%. Among the most affected CNs: CN 3, CN 5 and CN 7 were more prone to completely recover, respectively in 60.0%, 70.0% and 69.2%.Conclusions. Surgical removal of BSCs is feasible in experienced hands with acceptable morbidity and good outcome. Early surgery and single bleeding were associated with better surgical results.

Relationship between severity of lumbar disc disease and disability scores in sciatica patients.

OBJECTIVE To study the association between the clinical examination and the radiological assessment of lumbar disc disease in patients with sciatica. METHODS The study included 394 consecutive sciatica patients. The patients’ disabilities were evaluated by a visual analog pain scale, the Prolo functional-economic rating scale, the modified Roland-Morris disability questionnaire, and the health-related quality of life short form (SF-36) questionnaire. Radiological imaging findings were independently classified according to the Modic criteria into five groups of increasing severity of disc disease. Stepwise multivariate logistic regression was used to determine which scores were significant independent predictors of a severe disc disease (extrusion or sequestration). RESULTS Of these patients, 9.6% had no disc disease, 3.3% had a bulging, 11.4% had a protrusion, 68.5% had an extrusion, and 7.1% had a disc sequestration. Statistically significant positive linear associations with the severity of disc disease were found for the leg pain scale, the Roland-Morris and Prolo disability scales, and the SF-36 scores related to physical functioning, physical role, and bodily pain (all P < 0.005). A poor (<5) Prolo score (odds ratio, 2.91; 95% confidence interval, 1.74–4.87), a higher leg pain score (odds ratio, 1.16 per centimeter increase; 95% confidence interval, 1.07–1.27), and a lower low back pain score (odds ratio, 0.90 per centimeter decrease; 95% confidence interval, 0.82–0.98) were retained in the multivariate logistic model as independent predictors of severe disc disease. CONCLUSION The positive correlation between disability status and imaging findings validates both assessment methods. Routine use of disability scores brings a useful contribution to the assessment of sciatica patients.

Unusual complications at iliac crest bone graft donor site: experience with two cases.

OBJECTIVE AND IMPORTANCE Two cases of fracture of the iliac crest after graft harvesting are presented. Only six such cases have been reported in the literature, although more than 100,000 such procedures are performed each year in the United States alone. This complication adds to the morbidity of the procedure for which the graft is taken. Its avoidance by an appropriate harvesting technique will reduce patient disability and shorten hospital stay. CLINICAL PRESENTATION A 56-year-old man who worked as a mechanic underwent anterior cervical discectomies and fusion at C5-C6 and C6-C7 for spondylotic radiculopathies. Another patient, a 48-year-old man, required mandibular reconstruction for squamous cell carcinoma. Both grafts were harvested from the iliac crest using osteotomies. On the 9th and 3rd postoperative days, respectively, each patient developed groin pain while walking, associated with marked tenderness over the graft donor sites. X-rays showed fractured iliac crests. INTERVENTION Apart from bed rest for pain, no specific treatment was required. CONCLUSION The use of the osteotome weakens the iliac crest, leading to stress fractures caused by the pulling action of the attached muscles. To prevent this from happening, we recommend the use of the oscillating saw, leaving a 3-cm spike of iliac crest anteriorly. Nevertheless, this complication has a good long-term outcome.

The Influence of Preoperative Back Pain on the Outcome of Lumbar Decompression Surgery

Study Design. Prospective study with 12-month follow-up. Objective. To examine how the relative severity of low back pain (LBP) to leg/buttock pain (LP) influences the outcome of decompression surgery for spinal stenosis. Summary of Background Data. Decompression surgery is a common treatment for lumbar spinal canal stenosis, with generally good outcome. However, concomitant LBP at presentation can make it difficult to decide whether decompression alone will result in a good overall outcome. Methods. The Spine Society of Europe Spine Tango system was used to acquire the data from 221 patients. Inclusion criteria were lumbar degenerative spinal stenosis, first-time surgery, maximum 3 affected levels, and decompression as the only procedure. Before and 12 months after surgery, patients completed the multidimensional Core Outcome Measures Index (COMI; includes 0–10 LP and LBP scales); at 12 months, global outcome was rated on a Likert-scale and dichotomized into “good” and “poor” groups. Results. There was a low but significant positive correlation between baseline LP-minus-LBP scores and both improvement in the multidimensional COMI score after 12 months (r = 0.21, P = 0.003) and the score on the 12-month global outcome scale (r = 0.19, P = 0.007). In the good outcome group, mean baseline LP was 2.3 (±3.7) points higher than LBP; in the poor group, the corresponding value was 0.8 (±3.4) (P = 0.01 between groups). In multivariate regression analyses (controlling for age, gender, comorbidity), baseline LBP intensity was the most significant predictor of the 12-month COMI score, and preoperative LP-minus-LBP score of the global outcome (each P < 0.05). Conclusion. Overall, greater back pain relative to LP at baseline was associated with a significantly worse outcome after decompression. This finding seems intuitive, but has rarely been quantified in the many predictor studies conducted to date. Consideration of relative LBP and LP scores may assist in clinical decision-making and in establishing realistic patient expectations.

The validity of multimodal intraoperative monitoring (MIOM) in surgery of 109 spine and spinal cord tumors

In a prospective study of 109 patients with tumor of the spine MIOM was performed during the surgical procedure between March 2000 and December 2005. To determine the sensitivity and specificity of MIOM techniques used to monitor spinal cord and nerve root function during surgical procedure of spinal tumors. MIOM become an integrated procedure during surgical approach to intramedullar and extramedullar spine tumors. The combination of monitoring ascending and descending pathways may provide more sensitive and specific results than SEP alone giving immediate feedback information regarding any neurological deficit during the operation. Intraoperative sensory spinal and cerebral evoked potential combined with EMG recordings and motor evoked potential of the spinal cord and muscles were evaluated and compared with postoperative clinical neurological changes. One hundred and nine consecutive patients with spinal tumors of different aetiologies were monitored by the means of MIOM during the entire surgical procedure. Eighty-two patients presented true negative findings while two patients monitored false negative, one false positive and 24 patients true positive findings where neurological deficits after the operation were present. All patients with neurological deficit recovered completely or to pre-existing neurological situation. The sensitivity of MIOM applied during surgery of spinal tumors has been calculated of 92% and specificity 99%. Based upon the results of the study MIOM is an effective method of monitoring the spinal cord and nerve root function during surgical approach of spinal tumors and consequently can reduce or prevent the occurrence of postoperative neurological deficit.

Appropriateness of surgery for sciatica: reliability of guidelines from expert panels.

Study Design. Reliability study of guidelines development. Objective. To compare criteria for low back surgery between two expert panels. Background. Reliability of expert panels for determining appropriateness of indications for surgical procedures has heretofore received little attention. Methods. Two multidisciplinary expert panels of similar composition were convened, in the United States and in Switzerland, to evaluate the appropriateness of 720 distinct clinical scenarios involving sciatica. Each indication was assigned to a category of appropriate, uncertain, and inappropriate. The appropriateness of the 720 theoretical scenarios were compared between the two panels, and both sets of criteria were applied to two series of actual cases. Results. Seventy-nine percent (n = 566) of the 720 theoretical indications were assigned to identical categories of appropriateness by both panels (&kgr; = 0.63;P < 0.001). Only 2 of the 720 scenarios elicited frank disagreement. The percentage of the 720 indications that were considered appropriate differed between the two panels (U.S.: 3%; Swiss: 11%, P < 0.001), as did the percentage of intrapanel agreement for indications (U.S.: 51%, Swiss: 64%, P < 0.001). When the same theoretical scenarios were matched with two series of actual cases (n = 181 and 149) agreement was moderate (&kgr; = 0.46) to fair (&kgr; = 0.30). Conclusion. There was substantial agreement on the appropriateness of surgery for theoretical cases of sciatica between independent expert panels from two countries. A better understanding of discordant ratings, especially for actual cases, should precede attempts at transposing recommendations emanating from a panel in one country to another.

Cervical Amyloidoma of C2: Case Report and Review of the Literature

Study Design. Second published report of a patient with amyloidoma of the upper cervical spine. Objectives. To describe a patient with rare radiculopathy to alert other physicians to consider amyloid tumor as a differential diagnosis of locally destructive spine lesions. Summary of Background Data. Localized amyloid tumor of the bone is a rare disease. Only seven cases of spine involvement have been reported. Appropriate tissue sampling is required to establish the diagnosis. Histopathologic examination shows pathognomonic apple‐green birefringence under polarized light. When bone is involved with amyloid, it is most commonly associated with multiple myeloma or other plasma cell‐dyscrasias. Method. This case was described, and pertinent literature was reviewed. Results. The patient showed persistent neurologic improvement after transoral complete tumor removal, followed by a secondary posterior stabilization procedure using transarticular C1‐C2 screws. Conclusions. Amyloidomas are benign lesions with no associated documented risk for the development of plasmocytoma‐related diseases. The clinical and radiographic manifestations of this lesion are nonspecific. A cure is possible with complete resection of the tumor and no adjuvant management procedures.