A single-institution experience with concurrent capecitabine and radiation therapy in gastrointestinal malignancies.

PURPOSE: We report our clinical experience with 32 patients receiving concurrent irradiation and capecitabine. METHODS AND MATERIALS: Medical records of patients with gastrointestinal malignancies treated with radiation and capecitabine therapy were reviewed. RESULTS: The population consisted of 20 males and 12 females, with a median age of 67.5 years (45-84 years) and adequate hepatic and bone marrow function. Histology was adenocarcinoma in all patients, except two with esophageal squamous carcinoma. Twenty-one patients received the regimen as adjuvant therapy, three received preoperative therapy, and 8 patients received therapy for palliation. The median dose of capecitabine was 1600 mg/m(2)/day (1200-2500 mg/m(2)/day) orally for 5 days per week for the duration of radiation therapy. Thirty patients received a total dose ranging from 45 Gy to 64 Gy over 4-6 weeks. Two previously radiated patients received total doses of 29.9 Gy and 46 Gy. Grade 3/4 toxicities observed were neutropenia in 3 patients and diarrhea, thrombocytopenia, fatigue, and myocardial infarction in 1 patient each. No treatment-related mortality was observed. Twenty of 21 patients (95.2%) who received adjuvant therapy continue to be in complete remission. Four of 11 (36%) evaluable patients demonstrated a response. CONCLUSION: Concurrent capecitabine and radiation were very well tolerated and warrant further investigation in prospective trials.

Implant volume as a prognostic variable in brachytherapy decision-making for malignant gliomas stratified by the RTOG recursive partitioning analysis.

PURPOSE: When an initial retrospective review of malignant glioma patients (MG) undergoing brachytherapy was carried out using the Radiation Therapy Oncology Group (RTOG) recursive partitioning analysis (RPA) criteria, it revealed that glioblastoma multiforme (GBM) cases benefit the most from implant. In the present study, we focused exclusively on these GBM patients stratified by RPA survival class and looked at the relationship between survival and implanted target volume, to distinguish the prognostic value of volume in general and for a given GBM class. METHODS AND MATERIALS: Between 1991 and 1998, 75 MG patients were treated with surgery, external beam radiation, and stereotactic iodine-125 (I-125) implant. Of these, 53 patients (70.7%) had GBMs, with 52 (98%) having target volume (TV) data for analysis. Stratification by RPA criteria showed 12, 26, 13, and 1 patients in classes III to VI, respectively. For analysis purposes, classes V and VI were merged. There were 27 (51.9%) male and 25 (48.1%) female patients. Mean age was 57.5 years (range 14-79). Median Karnofsky performance status (KPS) was 90 (range 50-100). Median follow-up time was 11 months (range 2-79). RESULTS: At analysis, 18 GBM patients (34.6%) were alive and 34 (65.4%) were dead. Two-year and 5-year survivals were 42% and 17.5%, respectively, with a median survival time (MST) of 16 months. Two-year survivals and MSTs for the implanted GBM patients compared to the RTOG database were as follows: 74% vs. 35% and 28 months vs. 17.9 months for class III; 32% vs. 15% and 16 months vs. 11.1 months for class IV; 29% vs. 6% and 11 months vs. 8.9 months for class V/VI. Mean implanted TV was 15.5 cc (range 0.8-78), which corresponds to a spherical implant diameter of 3.1 cm. Plotting survival as a function of 5-cc TV increments suggested a trend toward poorer survival as the implanted volume increases. The impact of incremental changes in TV on survival within a given RPA class of GBMs was compared to the RTOG database. Looking at absolute differences in MSTs: for classes III and IV, there was little effect of different TVs on survival; for class V/VI, a survival benefit to implantation was still seen at the target volume cutoff (TV > 25 cc). Within a given RPA class, no significant differences were found within class III; for class IV, the most significant difference was at 10 cc (p = 0.05); and for class V/VI, at 20 cc (p = 0.06). CONCLUSION: For all GBM patients, an inverse relationship between implanted TV size and median survival is suggested by this study. However, when GBM patients are stratified using the RTOG's RPA criteria, the prognostic effect of implant volume disappears within each RPA survival class. At the critical volume of 25 cc, which approximates an implant of 5-cm diameter (upper implantation limit of many CNS brachytherapy protocols), the "poorest" prognosis GBM patients stratified by RPA still demonstrate a survival benefit with implant. We suggest that any GBM patient meeting brachytherapy recognized size criteria be considered for I-125 implant.

Norplant expansion in Kenya.

Norplant is a long-acting contraceptive that has been introduced into family planning programs all over the world. Its efficacy, safety and acceptability in the introductory phases have been widely tested, and most studies point to the need for good provider training in insertion and removal; good client counseling on side effects, suitable client selection to limit early removal, and attention to client access to removal services. Some problems with the method in the developed world, and a belief that it is too costly for developing countries, have led to a waning of support by international donors. Few studies have examined how service delivery expansion in the developing world can minimise and address potential problems as well as maintain Norplant's cost-effective edge against other methods. We examine the expansion of Norplant services in Kenya between 1992 and 1996, specifically in relation to client access to services, removal issues, and cost. Well-supervised and careful expansion has resulted in quality services being provided at more than 70 sites in the country. Early removal is limited, removals seem to have posed few problems, and Norplant offers a welcome and cost-effective addition to the family planning method mix.

Use of the RTOG recursive partitioning analysis to validate the benefit of iodine-125 implants in the primary treatment of malignant gliomas.

PURPOSE: To date, numerous retrospective studies have suggested that the addition of brachytherapy to the conventional treatment of malignant gliomas (MG) (surgical resection followed by radiotherapy +/- chemotherapy) leads to improvements in survival. Two randomized trials have suggested either a positive or no survival benefit with implants. Critics of retrospective reports have suggested that the improvement in patient survival is due to selection bias. A recursive analysis by the RTOG of MG trials has stratified MG patients into 6 prognostically significant classes. We used the RTOG criteria to analyze the implant data at Wayne State University to determine the impact of selection bias. METHODS AND MATERIALS: Between July 1991 and January 1998, 75 patients were treated with a combination of surgery, radiotherapy, and stereotactic I-125 implant as primary MG management. Forty-one (54.7%) were male; 34 (45.3%) female. Median age was 52 years (range 4-79). Twenty-two (29.3%) had anaplastic astrocytoma (AA); 53 (70.7%), glioblastoma multiforme (GBM). Seventy-two patients had data making them eligible for stratification into the 6 RTOG prognostic classes (I-VI). Median Karnofsky performance status (KPS) was 90 (range 50-100). There were 14, 0, 14, 31, 12, and 1 patients in Classes I to VI, respectively. Median follow-up time for AA, GBM, and any surviving patient was 29, 12.5, and 35 months, respectively. RESULTS: At analysis, 29 (40.3%) patients were alive; 43 (59.7%), dead. For AA and GBM patients, 2-year and median survivals were: 58% and 40%; 38 and 17 months, respectively. For analysis purposes, Classes I and II, V and VI were merged. By class, the 2-year survival for implanted patients compared to the RTOG data base was: III--68% vs. I--76%; III--74% vs. 35%; IV--34% vs. 15%; V/VI--29% vs. V--6%. For implant patients, median survival by class was (in months): I/II--37; III--31; IV--16; V/VI--11. CONCLUSION: When applied to MG patients receiving permanent I-125 implant, the criteria of the RTOG recursive partitioning analysis are a valid tool to define prognostically distinct survival groups. As reflected in the RTOG study, a downward survival trend for the implant patients is seen from "best to worse" class patients. Compared to the RTOG database, median survival achieved by the addition of implant is improved most demonstrably for the poorer prognostic classes. This would suggest that selection bias alone does not account for the survival benefit seen with I-125 implant and would contradict the notion that the patients most eligible for implant are those gaining the most benefit from the treatment. In light of the contradictory results from two randomized studies and given the present results, further randomized studies with effective stratification are required since the evidence for a survival benefit with brachytherapy (as seen in retrospective studies) is substantial.

Lipid peroxidation does not appear to be a factor in late radiation injury of the cervical spinal cord of rats.

PURPOSE: We tested the role of lipid peroxidation in the demyelination and white matter necrosis associated with radiation injury of the central nervous system. METHODS AND MATERIALS: We irradiated the cervical spinal cords of female F344 rats (23 Gy) and assayed for the accumulation of the peroxidation byproducts malondialdehyde and hydroxyeicosatetraenoic acids, and for the consumption of the endogenous free radical scavengers vitamins E and C. We further tested the role of lipid peroxidation in radiation injury of the central nervous system by determining the sensitivity of the cervical spinal cord to radiation in rats on diets containing deficient, normal, and supplemental levels of the antioxidant vitamin E. Rats were placed on these diets at 4 weeks of age and irradiated (18.5-21.5 Gy) 16 weeks later. RESULTS: During the 5 months between irradiation and the onset of paralysis, no accumulation of peroxidation byproducts or consumption of endogenous scavengers was seen in the cervical spinal cords of the irradiated rats. The cervical spinal cords of some of the rats placed on the diets with deficient, normal, and supplemental levels of vitamin E were analyzed at the time of irradiation and contained 197 +/- 57, 501 +/- 19, and 717 +/- 35 pmol vitamin E/mg protein, respectively. Despite the statistical differences in these levels, the radiation sensitivity of the cervical spinal cord (ED50 for white matter necrosis) in rats receiving the three diets was not different (20.4, 20.7, and 20.6 Gy). CONCLUSION: These data do not support a role for free radical-induced lipid peroxidation in the white matter damage seen in radiation injury of the central nervous system.

Polyamine accumulation and vasogenic oedema in the genesis of late delayed radiation injury of the central nervous system (CNS).

Polyamine (PA) accumulation has been associated with blood-brain barrier (BBB) disruption and vasogenic oedema after cold injury. PAs and water content were measured in a rat spinal cord model of late-delayed radiation injury and were found to be elevated at paralysis. The elevated PA levels could be significantly reduced by treatment with difluoromethylornithine (DFMO). In unirradiated rats DFMO reduced putrescine to undetectable levels after 10-12 weeks. These data suggest that blockade of PA synthesis may be useful in treating the vasogenic oedema of radiation injury and may improve CNS radiation tolerance.

Medical student education in life-support skills.

A life-support skills course designed to facilitate competent decision making during emergency care situations has been developed for third-year medical students at the University of North Carolina at Chapel Hill School of Medicine. The objective of the one-week course is to combine the knowledge acquired in the basic sciences with the performance skills required in the clinical setting. This is achieved through the use of a variety of instructional strategies, including lectures, reading periods, and laboratory exercises. A scientific approach to the teaching of life-support skills is incorporated, educational objectives are defined, methods of achieving the educational objectives are provided, and an evaluation system is used to determine the effectiveness of teaching. After successful completion of the training program, the student is better able to deliver competent emergency medical care.

Anesthesiology and the graduating medical student: a national survey.

Each year, many anesthesiology housestaff positions remain vacant or are filled by foreign medical graduates. While possibly reflecting an overabundance of such housestaff positions, this situation also suggests a lack of U.S. student interest in anesthesiology. To investigate this phenomenon, the authors conducted a survey of American medical school graduates of 1976. The results reveal that 65% of students receive minimal or no systematic exposure to anesthesiology or anesthesiologists. When such exposure occurs, it comes after many students have developed strong specialty preferences. Many students saw anesthesiology as limited in scope and unchallenging and indicated that they did not select anesthesiology because it entails insufficient primary patient care. Contrasts between those entering and not entering anesthesiology suggest, however, that certain variables which are subject to manipulation--such as amount, timing, and content of exposure to anesthesiology--could alter student attitudes and potentially generate increased student interest in the specialty.

Fatal hepatic necrosis after halothane anesthesia in a boy with juvenile rheumatoid arthritis: a case report.

Hepatitis from halothane is usually diagnosed by excluding other possible causes. Whether preexisting hepatic damage, which can occur in certain autoimmune disorders, contraindicates the use of halothane has yet to be proven. The case of a 14-year-old boy with early-onset juvenile rheumatoid arthritis who developed fatal hepatic necrosis 13 days after halothane anesthesia is presented.

Cardiorespiratory effects of a balanced anesthetic technique in outpatient general anesthesia.

Detailed measures have been made of the cardiorespiratory effects of a balanced general anesthetic technique on ten young patients undergoing oral surgery. The combination of fentanyl, diazepam, and atropine followed by N2O/O2 and methohexital resulted in a respiratory hyperoxic state throughout surgery and there was no evidence of hypercardia at any anesthesia stage. Cardiovascular stability was judged to be generally superior to that reported for techniques that have relied on methohexital without premedication. This balanced general anesthetic technique offers the oral surgeon-anesthetist a safe, effective, and practical alternative to techniques that rely on more potent anesthetic gases.

Cardiovascular effects of cannabinol during oral surgery.

Fifty-five clinical trials were conducted to determine the cardiovascular combined effects of stressful oral surgery and systemic cannabinols. In a first study, delta9-tetrahydrocannabinol (THC) was given IV as a premedicant and compared with diazepam and with a placebo. A classic dose-related tachycardia followed THC injection. The peak heart rate response of patients premedicated with 0.044 mg/kg THC was 24.1% higher (p less than 0.05) than the peak effect for a nonsurgerized control group, suggesting a synergistic effect between THC and surgical stress. A predisposition to syncopal hypotension followed THC premedication, and antiarrhythmic effects were observed after large doses. The injection of local anesthetic preparations containing epinephrine did not alter THC cardiovascular response. An apparent drug interaction was observed, however, in a second study, in patients given general anesthesia within 72 hours after smoking marijuana. These patients demonstrated sustained abnormal postoperative tachycardia when compared with control nonsmokers, an effect which may have resulted from an interaction between stored cannabinol metabolites and atropine administered as part of the anesthetic technic. It was concluded that THC had no particular advantage over diazepam or placebo as a premedicant. Further, THC altered the patients' adaptivity to stress and interacted undesirably with other anesthetic medications.

Ambulatory surgery in a university setting.

Establishment of an ambulatory anesthesia and surgery program in a university teaching hospital presents difficulties. A successful program of this nature, the "Day Op program," was begun at the North Carolina Memorial Hospital in December 1972. Through December 1974, of all surgery performed in our operating rooms, 2,590 cases, (17%) were Day Op cases. Various types of anesthesia were used, and a high percentage of endotracheal intubations were performed. The hospital admission rate was 1.54%. Many difficulties were encountered, and much satisfaction was obtained, in the management of the program. The Day Op room has proved to be a major part of the success of the program.