Randomized Controlled Trial of Enhanced Recovery Program Dedicated to Elderly Patients After Colorectal Surgery.

BACKGROUND: Enhanced recovery program is a multimodal, multidisciplinary-team, evidence-based care approach to reduce perioperative surgical stress, decrease morbidity and hospital stay, and improve recovery after surgery. This program may be most beneficial for elderly (≥70 y), but sparse series have investigated this question. OBJECTIVE: Feasibility and efficiency of a dedicated enhanced recovery program in the elderly as compared with standard care were studied. DESIGN: This was a nonblinded, randomized controlled study. SETTINGS: This study was conducted in a single high-volume university hospital. PATIENTS: A total of 150 eligible elderly patients undergoing elective colorectal surgery were included. INTERVENTIONS: Enhanced recovery after colorectal elective surgery in elderly patients was studied. MAIN OUTCOME MEASURES: The primary outcome was 30-day postoperative morbidity. Additional outcomes included hospital stay, readmission, postoperative pain, opioid consumption, independence preservation, and protocol compliance. RESULTS: An enhanced recovery program reduces postoperative morbidity according to Clavien-Dindo classification by 47% as compared with standard care (35% vs 65%; p = 0.0003), total number of complications (54 vs 118; p = 0.0003), and infectious complications (13 vs 29; p = 0.001). No anastomotic leak was recorded in the enhanced recovery group versus 5 for the standard group (p = 0.01). The enhanced recovery program resulted in shorter hospital stay (7 vs 12 d; p = 0.003) and better independence preservation (home discharge, 87% vs 67%; p = 0.005). A high protocol compliance of 77.2% could be achieved in this population. According to multivariate analysis, enhanced recovery program was strongly associated with reduced morbidity (OR = 0.23 (95% CI, 0.09-0.57); p = 0.001), less severe complications (OR = 0.36 (95% CI, 0.15-0.84); p = 0.02), and shorter hospital stay (OR = 2.07 (95% CI, 1.33-3.22); p = 0.001). LIMITATIONS: Limitations were a single-center recruitment and the impossibility of subject or healthcare professional blinding attributed to the nature of this multimodal program. CONCLUSIONS: Enhanced recovery program is safe and improves postoperative recovery in elderly patients with decreased morbidity, shorter hospital stay, and better maintenance of independence. It should therefore be considered as a standard of care for elective colorectal surgery in elderly patients. See Video Abstract at http://links.lww.com/DCR/A981. TRIAL REGISTRATION: clinicaltrials.gov identifier: NCT01646190. ENSAYO CONTROLADO ALEATORIZADO DE UN PROGRAMA DE RECUPERACIÓN INTENSIFICADA DEDICADO A PACIENTES DE EDAD AVANZADA DESPUÉS DE CIRUGÍA COLORECTAL: El Programa de Recuperación Intensificada es un enfoque de atención multimodal, multidisciplinaria y basada en evidencia para reducir el estrés quirúrgico perioperatorio, disminuir la morbilidad y la estancia hospitalaria, y mejorar la recuperación después de la cirugía. Este programa puede ser más beneficioso para las personas mayores (≥70 años), pero pocas series han investigado esta pregunta. OBJETIVO: Viabilidad y eficiencia del Programa de Recuperación Intensificada dedicado en personas de edad avanzada en comparación con la atención estándar. DISEÑO:: Este fue un estudio controlado, aleatorizado, sin método ciego. ESCENARIO: Este estudio se realizó en un único hospital universitario de alto volumen. PACIENTES: Un total de 150 pacientes de edad avanzada elegibles sometidos a cirugía colorrectal electiva fueron incluidos. INTERVENCIONES: Recuperación Intensificada después de cirugía electiva colorrectal en pacientes de edad avanzada. PRINCIPALES MEDIDAS DE RESULTADO: El resultado primario fue la morbilidad postoperatoria a 30 días. Los resultados adicionales incluyeron estancia hospitalaria, reingreso, dolor postoperatorio, consumo de opioides, preservación de la independencia y cumplimiento del protocolo. RESULTADOS: El Programa de Recuperación Intensificada reduce la morbilidad postoperatoria según la clasificación de Clavien-Dindo en un 47% en comparación con la atención estándar (35% vs 65%; p = 0.0003), número total de complicaciones (54 vs 118; p = 0.0003) y complicaciones infecciosas (13 vs 29; p = 0.001). No se registró ninguna fuga anastomótica en el grupo de Recuperación Intensificada frente a 5 para el grupo estándar (p = 0.01). El Programa de Recuperación Intensificada dio como resultado una estancia hospitalaria más corta (7 contra 12 días; p = 0.003) y una mejor conservación de la independencia (alta hospitalaria: 87% vs 67%; p = 0.005). Se pudo lograr un alto cumplimiento del protocolo del 77.2% en esta población. De acuerdo con el análisis multivariable, el Programa de Recuperación Intensificada se asoció fuertemente con la reducción de morbilidad (OR = 0.23; IC 95%: 0.09-0.57; p = 0.001), menos complicaciones graves (OR = 0.36; IC 95%: 0.15-0.84; p = 0.02) y estancia hospitalaria más corta (OR = 2.07; IC 95%: 1.33-3.22; p = 0.001). LIMITACIONES: Las limitaciones fueron un centro único de reclutamiento y la imposibilidad de que los pacientes o el profesional de la salud tuvieran cegamiento debido a la naturaleza de este programa multimodal. CONCLUSIONES: El Programa de recuperación Intensificada es seguro y mejora la recuperación postoperatoria en pacientes de edad avanzada, con menor morbilidad, menor estancia hospitalaria y mejor mantenimiento de la independencia. Por lo tanto, debe considerarse como un estándar de atención para la cirugía colorrectal electiva en pacientes de edad avanzada. Vea el Resumen en video en http://links.lww.com/DCR/A981.

Intestinal obstruction following use of laparoscopic barbed suture: a new complication with new material?

Small bowel obstruction is a common pathology. Among the various etiologies, foreign material has been incriminated as a possible but uncommon cause. Recently, barbed suture has been successfully introduced in various surgical fields and has been reported as safe as standard suture. We report herein a case of intestinal obstruction due to the laparoscopic use of barbed suture during a promontofixation. Barbed suture has the risk of entrapping the small bowel. The surgeon should keep in mind this hypothetical problem and a high index of suspicion is needed to diagnose and treat quickly this potentially severe complication.

Female population perception of conventional laparoscopy, transumbilical LESS, and transvaginal NOTES for cholecystectomy.

BACKGROUND: Recent population survey has shown a preference for transumbilical laparoendoscopic single-site surgery (U-LESS) compared with natural orifice transluminal endoscopic surgery (NOTES) for cholecystectomy, assuming similar surgical risk. This study was designed to evaluate the perception and preference of women regarding conventional laparoscopy, U-LESS, and transvaginal NOTES (TV-NOTES) with particular interest to access perception. METHODS: An anonymous questionnaire on laparoscopic, U-LESS, and TV-NOTES cholecystectomy, without regards to risks or advantages, was given to female medical/paramedical staff (n=100), patients (n=100), and the general population (n=100). Women participants (median age, 35 (range, 16-79) years) were queried about preference, perception of the different accesses, and personal informations. Of the respondents, 54% had children, 79% had stable relationships, and 96% were sexually active (vaginal intercourse). RESULTS: With similar operative risk, 87% preferred U-LESS, 4% TV-NOTES and 8% laparoscopy. LESS/NOTES choice was influenced by a desire of improved cosmetics (82%) and lower pain (44%). 96% had worries regarding transvaginal access, among them: dyspareunia (68%), decreased sensibility during intercourse (43%), refuse of short-term sexual abstinence (40%), and infertility (23%). Transumbilical access evocated worries in 35%: umbilical pain (19%), postoperative umbilical sensibility (15%), and incisional hernia (11%). Postoperative intercourse abstinence after TV-NOTES evocated worries in 76% (defined as 3 weeks in survey): feel less attractive (40%), less feminine (32%), tension with their intimate (35%), lover non-acceptation (20%), possible abortion of new relationship (26%), and feel less comfortable socially (16%). CONCLUSIONS: The high acceptation rate for U-LESS approach compared with TV-NOTES may be related to fears regarding postoperative sexuality and fertility. The importance of temporary postoperative sexual abstinence (vaginal intercourse) is high and may be difficult to influence. Future research on TV-NOTES should focus on the access risk to be able to scientifically reassure our patients. For now, U-LESS seems to be favor compared with TV-NOTES for cholecystectomy in female patients.

Population perception of surgical safety and body image trauma: a plea for scarless surgery?

BACKGROUND: Laparoendoscopic single-site surgery (LESS) and natural orifice translumenal endoscopic surgery (NOTES) are prospected as the future of minimally invasive surgery. While scarless surgery (NOTES and LESS) is gaining increasing popularity, perception of these approaches should be investigated. METHODS: An anonymous questionnaire describing laparoscopy, LESS, and NOTES was given to medical staff (n=120), paramedical staff (n=100), surgical patients (n=100), and the general population (n=100). The survey participants (median age, 37 years; range, 18-81 years) were queried about their expectations for surgical treatment and their approach preference. RESULTS: The first concern of the survey responders was the risk of surgical complications (92%). When asked about the respective importance of surgical safety, cure, and cosmetics, cure was placed first by 74%, safety by 33%, and cosmetics by 3%. These results were not influenced by sex, age, prior surgery or endoscopy, or education. When operative risk was similar, 90% of the participants preferred a scarless approach (75% preferred LESS and 15% preferred NOTES) to laparoscopy. The scarless approach preference was significantly higher among the younger participants (age<40 years; p=0.026), whereas sex showed no influence. The LESS preference was significantly higher among patients and the general population (86%) than among medical (67%) and paramedical (70%) staffs (p<0.001). A decreasing trend of preference for LESS and NOTES was observed with increased procedural risks. CONCLUSION: Although cure and safety remain the main concern, the population has a favorable perception of scarless surgery, even in the case of increased procedural risk, with LESS favored over NOTES. Such a popular adoption of scarless surgery should warrant the promotion of further research, technological innovations, and the establishment of surgeon training to improve its safety.

Elevated levels of MIC-1/GDF15 in the cerebrospinal fluid of patients are associated with glioblastoma and worse outcome.

For patients with brain tumors identification of diagnostic and prognostic markers in easy accessible biological material, such as plasma or cerebrospinal fluid (CSF), would greatly facilitate patient management. MIC-1/GDF15 (growth differentiation factor 15) is a secreted protein of the TGF-beta superfamily and emerged as a candidate marker exhibiting increasing mRNA expression during malignant progression of glioma. Determination of MIC-1/GDF15 protein levels by ELISA in the CSF of a cohort of 94 patients with intracranial tumors including gliomas, meningioma and metastasis revealed significantly increased concentrations in glioblastoma patients (median, 229 pg/ml) when compared with control cohort of patients treated for non-neoplastic diseases (median below limit of detection of 156 pg/ml, p < 0.0001, Mann-Whitney test). However, plasma MIC-1/GDF15 levels were not elevated in the matching plasma samples from these patients. Most interestingly, patients with glioblastoma and increased CSF MIC-1/GDF15 had a shorter survival (p = 0.007, log-rank test). In conclusion, MIC-1/GDF15 protein measured in the CSF may have diagnostic and prognostic value in patients with intracranial tumors.

[Interest of enhanced recovery programs in the elderly during total hip arthroplasty A systematic review]. / Utilité des programmes de réhabilitation améliorée chez le sujet âgé lors des arthroplasties totales de hanche Revue systématique de la littérature.

Enhanced recovery after surgery (ERAS) is an evident advance in the management of patients. Its feasibility and its effectiveness have been little analyzed in elderly's orthopedics. The aim of this systematic review of the literature was to analyze the feasibility (realization of classic ERAS items) and the efficiency (length of stay, morbidity and mortality) of ERAS in the elderly during total arthroplasty hip. MATERIALS AND METHODS: A bibliographic search was performed with PubMed, Medline, CINAHL, Cochrane and Embase, using keywords "total hip arthroplasty", "orthopedics surgery", "fast track", "enhanced recovery after surgery", and" elderly ". Seventy-two articles were listed and 47 fully analyzed by 2 independent authors. RESULTS: Thirty-two articles were selected. All the articles demonstrated ERAS feasibility in the elderly. The most frequently performed items were: preoperative information, spinal anesthesia and local or regional anesthetic infiltrations, multimodal analgesia with opioids sparing. Early stand-up is desirable but more difficult to achieve than in younger. Compared with traditional management, ERAS decreases the average length of stay without increasing complications, re-admissions and mortality rates. Medico-economic analyzes would be in favor of a reduction in the overall cost. The elderly's adherence to ERAS program depends on information's quality provided at the time of the consultation. CONCLUSION: The application of ERAS program in total hip arthroplasty in the elderly is feasible and efficient to reduce hospital stay and morbidity without increasing the complication rates. Protocols must be adapted to the particularities of this population.

Perfusion and diffusion MRI of glioblastoma progression in a four-year prospective temozolomide clinical trial.

PURPOSE: This study was performed to determine the impact of perfusion and diffusion magnetic resonance imaging (MRI) sequences on patients during treatment of newly diagnosed glioblastoma. Special emphasis has been given to these imaging technologies as tools to potentially anticipate disease progression, as progression-free survival is frequently used as a surrogate endpoint. METHODS AND MATERIALS: Forty-one patients from a phase II temolozomide clinical trial were included. During follow-up, images were integrated 21 to 28 days after radiochemotherapy and every 2 months thereafter. Assessment of scans included measurement of size of lesion on T1 contrast-enhanced, T2, diffusion, and perfusion images, as well as mass effect. Classical criteria on tumor size variation and clinical parameters were used to set disease progression date. RESULTS: A total of 311 MRI examinations were reviewed. At disease progression (32 patients), a multivariate Cox regression determined 2 significant survival parameters: T1 largest diameter (p < 0.02) and T2 size variation (p < 0.05), whereas perfusion and diffusion were not significant. CONCLUSION: Perfusion and diffusion techniques cannot be used to anticipate tumor progression. Decision making at disease progression is critical, and classical T1 and T2 imaging remain the gold standard. Specifically, a T1 contrast enhancement over 3 cm in largest diameter together with an increased T2 hypersignal is a marker of inferior prognosis.

Primary spinal epidural lymphoma: patients' profile, outcome, and prognostic factors: a multicenter Rare Cancer Network study.

PURPOSE: To assess the clinical profile, treatment outcome, and prognostic factors in primary spinal epidural lymphoma (PSEL). METHODS AND MATERIALS: Between 1982 and 2002, 52 consecutive patients with PSEL were treated in nine institutions of the Rare Cancer Network. Forty-eight patients had an Ann Arbor stage IE and four had a stage IIE. Forty-eight patients underwent decompressive laminectomy, all received radiotherapy (RT) with (n = 32) or without chemotherapy (n = 20). Median RT dose was 36 Gy (range, 6-50 Gy). RESULTS: Six (11%) patients progressed locally and 22 (42%) had a systemic relapse. At last follow-up, 28 patients were alive and 24 had died. The 5-year overall survival, disease-free survival, and local control were 69%, 57%, and 88%, respectively. In univariate analyses, favorable prognostic factors were younger age and complete neurologic response. Multivariate analysis showed that combined modality treatment, RT volume, total dose more than 36 Gy, tumor resection, and complete neurologic response were favorable prognostic factors. CONCLUSIONS: Primary spinal epidural lymphoma has distinct clinical features and outcome, with a relatively good prognosis. After therapy, local control is excellent and systemic relapse occurs in less than half the cases. Combined modality treatment appears to be superior to RT alone.

Cost of temozolomide therapy and global care for recurrent malignant gliomas followed until death.

Effectiveness and costs of care and treatment of recurrent malignant gliomas are largely unknown. In this study, 49 patients (32 males, 17 females; mean age, 49; age range, 23-79) were treated with temozolomide (TMZ) for recurrent or progressive malignant gliomas after standard radiation therapy. Cost assessment (payer's perspective) singled out treatment for first recurrence and all costs of care until death. We computed personnel costs as wages; drugs, imaging, and laboratory tests as prices; and hospitalizations as day rates. Patients were administered a median of five TMZ cycles at recurrence. Drug acquisition costs amounted to euro 2206 per cycle (76% of total costs). Seven patients showed no second recurrence (two are still alive), 16 received no further chemotherapy and died after 3.9 months, and 26 received second-line chemotherapy. After the second progression, median survival was 4.0 months (95% confidence interval, 1.8-6.1). Overall monthly costs of care varied between euro 2450 and euro 3242 among the different groups, and median cost-effectiveness and cost utility ranged from euro 28,817 to euro 38,450 and from euro 41,167 to euro 53,369 per life of year and per quality-adjusted life-year gained, respectively. We conclude that despite high TMZ drug acquisition costs, care of recurrent malignant gliomas is comparable to other accepted therapies.

Plasma and cerebrospinal fluid population pharmacokinetics of temozolomide in malignant glioma patients.

PURPOSE: Scarce information is available on the brain penetration of temozolomide (TMZ), although this novel methylating agent is mainly used for the treatment of malignant brain tumors. The purpose was to assess TMZ pharmacokinetics in plasma and cerebrospinal fluid (CSF) along with its inter-individual variability, to characterize covariates and to explore relationships between systemic or cerebral drug exposure and clinical outcomes. EXPERIMENTAL DESIGN: TMZ levels were measured by high-performance liquid chromatography in plasma and CSF samples from 35 patients with newly diagnosed or recurrent malignant gliomas. The population pharmacokinetic analysis was performed with nonlinear mixed-effect modeling software. Drug exposure, defined by the area under the concentration-time curve (AUC) in plasma and CSF, was estimated for each patient and correlated with toxicity, survival, and progression-free survival. RESULTS: A three-compartment model with first-order absorption and transfer rates between plasma and CSF described the data appropriately. Oral clearance was 10 liter/h; volume of distribution (V(D)), 30.3 liters; absorption constant rate, 5.8 h(-1); elimination half-time, 2.1 h; transfer rate from plasma to CSF (K(plasma-->CSF)), 7.2 x 10(-4)h(-1) and the backwards rate, 0.76 h(-1). Body surface area significantly influenced both clearance and V(D), and clearance was sex dependent. The AUC(CSF) corresponded to 20% of the AUC(plasma). A trend toward an increased K(plasma-->CSF) of 15% was observed in case of concomitant radiochemotherapy. No significant correlations between AUC in plasma or CSF and toxicity, survival, or progression-free survival were apparent after deduction of dose-effect. CONCLUSIONS: This is the first human pharmacokinetic study on TMZ to quantify CSF penetration. The AUC(CSF)/AUC(plasma) ratio was 20%. Systemic or cerebral exposures are not better predictors than the cumulative dose alone for both efficacy and safety.

Clinical trial substantiates the predictive value of O-6-methylguanine-DNA methyltransferase promoter methylation in glioblastoma patients treated with temozolomide.

PURPOSE: In the setting of a prospective clinical trial, we determined the predictive value of the methylation status of the O-6-methylguanine-DNA methyltransferase (MGMT) promoter for outcome in glioblastoma patients treated with the alkylating agent temozolomide. Expression of this excision repair enzyme has been associated with resistance to alkylating chemotherapy. EXPERIMENTAL DESIGN: The methylation status of MGMT in the tumor biopsies was evaluated in 38 patients undergoing resection for newly diagnosed glioblastoma and enrolled in a Phase II trial testing concomitant and adjuvant temozolomide and radiation. The epigenetic silencing of the MGMT gene was determined using methylation-specific PCR. RESULTS: Inactivation of the MGMT gene by promoter methylation was associated with longer survival (P = 0.0051; Log-rank test). At 18 months, survival was 62% (16 of 26) for patients testing positive for a methylated MGMT promoter but reached only 8% (1 of 12) in absence of methylation (P = 0.002; Fisher's exact test). In the presence of other clinically relevant factors, methylation of the MGMT promoter remains the only significant predictor (P = 0.017; Cox regression). CONCLUSIONS: This prospective clinical trial identifies MGMT-methylation status as an independent predictor for glioblastoma patients treated with a methylating agent. The association of the epigenetic inactivation of the DNA repair gene MGMT with better outcome in this homogenous cohort may have important implications for the design of future trials and supports efforts to deplete MGMT by O-6-benzylguanine, a noncytotoxic substrate of this enzyme.

Segmental duodenectomy for gastrointestinal stromal tumor of the duodenum.

AIM: To evaluate the results of segmental duodenectomy (SD) and pancreaticoduodenectomy (PD) for duodenal gastrointestinal stromal tumor (GIST) and help clinicians with surgical management. METHODS: All patients who underwent surgery for non-metastatic GIST of the duodenum in a single institution since 2000 were prospectively followed up. Seven patients (median age 51 years, range: 41-73 years) were enrolled: five underwent SD and two underwent PD. RESULTS: All the patients had a complete resection (R0), with no postoperative morbidity and mortality. Among the SD group, GIST was classified as low risk in two patients, intermediate risk in two, and high risk in one, according to the Fletcher scale, (vs two high risk patients in the PD group). With a median follow-up of 41 (18-85) mo, disease-free survival (DFS) rates were 100% after SD and 0% after PD (P < 0.05). The median DFS was 13 mo in the PD group. CONCLUSION: Whenever associated with clear surgical margins, SD is a reliable and curative option for most duodenal GISTs, and is compatible with long-term DFS.

Single port access laparoscopic cholecystectomy (with video).

BACKGROUND: Single port access (SPA) surgery is a rapidly evolving field due to the complexity of NOTES (natural orifice translumenal endoscopic surgery). SPA combines the cosmetic advantage of NOTES and possibility to perform surgical procedure with standard laparoscopic instruments. We report a technique of umbilical SPA cholecystectomy using standard laparoscopic instruments and complying with conventional surgical principle and technique of minimally invasive cholecystectomy. METHODS: Preliminary, prospective experience of SPA cholecystectomy in 11 patients (median age, 46 (range, 27-63) years) scheduled for cholecystectomy was evaluated. Diagnoses for cholecystectomy were: symptomatic gallbladder lithiasis (n = 7), previous acute cholecystitis (n = 3), and biliary pancreatitis (n = 1). RESULTS: SPA cholecystectomy was feasible in all patients (median body mass index, 24 (range, 20-34) kg/m(2)) who were scheduled for preliminary experience using conventional laparoscopic instruments. Median operative time was 52 (range, 40-77) minutes. Intraoperative cholangiography was performed in all patients, except one, and was considered normal. No peroperative or postoperative complications were recorded. Median hospital stay was less than 24 h. CONCLUSIONS: SPA cholecystectomy is feasible and seems to be safe when performed by experienced laparoscopic surgeons using standard laparoscopic instrumentation. SPA cholecystectomy may be safer than the NOTES approach at this time. It has to be determined whether this approach would benefit patients, other than cosmesis, compared with standard laparoscopic cholecystectomy.

Importance of genetic diagnosis of DAX-1 deficiency: example from a large, multigenerational family.

BACKGROUND: Inactivating mutations of DAX-1 give rise to the X-linked form of adrenal hypoplasia congenita (AHC). Affected fetuses are at risk of early postnatal Addisonian crisis, but the variable phenotypic expression of DAX-1 insufficiency renders this diagnosis challenging. METHODS: We describe the familial transmission of AHC over several generations. The proband was diagnosed with adrenal insufficiency at age 3.5 years: molecular analysis revealed a novel, 373-bp deletion including the second exon of DAX-1. Given the familial history of several unexplained deaths in male infants related to the proband via his maternal great-grandmother, we hypothesized that all these boys had been affected with AHC. Another female member of the family being pregnant with a male fetus at the time, we performed DAX-1 analysis on the mother and the newborn. The mother was heterozygous for the deletion, and the newborn hemizygous: he presented an adrenal crisis at 10 days of life, and is now doing well on hormone replacement therapy. CONCLUSION: The unfortunate deaths of male infants at each generation of this family underlie the importance of early and precise diagnosis of this rare condition, stressing the value of genetic diagnosis in six potential female carriers of this family entering their reproductive years.

Can we afford to add chemotherapy to radiotherapy for glioblastoma multiforme? Cost-identification analysis of concomitant and adjuvant treatment with temozolomide until patient death.

BACKGROUND: Adding temozolomide (TMZ) to standard radiotherapy as a first-line therapy for glioma may increase costs to a disproportionate degree compared with the resulting survival benefits. METHODS: Forty-six consecutive patients (28 males and 18 females; median age, 52 years; age range, 24-70 years) received concomitant TMZ with radiotherapy for 6 weeks followed by adjuvant TMZ for 6 cycles, and they were followed until disease recurrence and then until death. The authors assessed the costs associated with the four phases of treatment from a hospital-centered perspective. RESULTS: Treatment was discontinued early in 3 patients, 9 patients, and 15 patients during concomitant TMZ, before adjuvant TMZ, and during adjuvant TMZ, respectively. Karnofsky index values varied between 85% (at the beginning of treatment) and 76% (at the end of treatment). The nature of care after disease recurrence was diverse. Overall survival ranged from 1.4 months to 64.3 months (median, 15.8 months) and was better if surgical debulking could be carried out before treatment. Global costs amounted to Euros 39,092 +/- Euros 21,948 (concomitant TMZ, Euros 14,539 +/- Euros 4998; adjuvant TMZ, Euros 13,651 +/- Euros 4320; follow-up, Euros 6363 +/- Euros 6917; and recurrence, Euros 12,344 +/- Euros 18,327), with 53% of these costs being related to the acquisition of TMZ; this represented an eightfold increase in cost compared with radiotherapy alone. CONCLUSIONS: TMZ may be an effective but costly adjuvant outpatient therapy for patients with glioblastoma multiforme. Definite cost-effectiveness/utility must be assessed in a randomized Phase III trial.