Some Additional Data That Might Be Useful for Diastasis Recti Assessment.

Background: Diastasis recti (DR) is characterized by separation of both rectus muscles and protrusion of the median bulging, but besides median bulging DR can also entail global abdominal bulging. On other note, DR classification is based on the width of divarication, but measurement values are different at rest and at effort due to muscle contraction. Aim of the study is to provide additional features concerning the type of bulging and the width of divarication. Methods: Findings were retrospectively drawn from the data prospectively collected in the records of a continuous cohort of 105 patients (89 females, 16 males) referred for diastasis and concomitant ventral hernia repair. Results: There was a median bulging alone in 45 (42.9%) cases, a global bulging alone in 18 (17.1%) cases, both types combined in 37 (35.2%) cases and no bulging in 5 (4.8%). On 55 patients with a global bulging, 51 were females. Tape measurements values of DR width were closer to the values measured on the CT scan at leg raise than at rest. The differences were significant at rest as well as at leg raise. Though the difference at rest was highly significant (p = 0.000), the difference at effort was not far from being not significant (p = 0.049). Conclusion: Besides median bulging, presence or absence of the global bulging should be included in DR assessment. The difference between width of divarication at rest and on exertion raises the question of which value should be used for DR classification. The question is worth being debated.

Patterns of integrating palliative care into standard oncology in an early ESMO designated center: a 10-year experience.

BACKGROUND: Integration of specialist palliative care (PC) into standard oncology care is recommended. This study investigated how integration at the Cantonal Hospital St. Gallen (KSSG) was manifested 10 years after initial accreditation as a European Society for Medical Oncology (ESMO) Designated Center (ESMO-DC) of Integrated Oncology and Palliative Care. METHODS: A chart review covering the years 2006-2009 and 2016 was carried out in patients with an incurable malignancy receiving PC. Visual graphic analysis was utilized to identify patterns of integration of PC into oncology based on the number and nature of medical consultations recorded for both specialties. A follow-up cohort collected 10 years later was analyzed and changes in patterns of integrating specialist PC into oncology were compared. RESULTS: Three hundred and forty-five patients from 2006 to 2009 and 64 patients from 2016 were included into analyses. Four distinct patterns were identified using visual graphic analysis. The 'specialist PC-led pattern' (44.9%) and the 'oncology-led pattern' (20.3%) represent disciplines that took primary responsibility for managing patients, with occasional and limited involvement from other disciplines. Patients in the 'concurrent integrated care pattern' (18.3%) had medical consultations that frequently bounced between specialist PC and oncology. In the 'segmented integrated care pattern' (16.5%), patients had sequences of continuous consultations provided by one discipline before alternating to a stretch of consultations provided by the other specialty. In the 2016 follow-up, while the 'oncology-led pattern' occurred significantly less frequently relative to the 'specialist PC-led pattern' and the 'segmented integrated care pattern', the 'concurrent integrated care pattern' emerged more frequently when compared with the 2006-2009 follow-up. CONCLUSION: The 'specialist PC-led pattern' was the most prominent pattern in this data. The 2016 follow-up showed that a growing number of patients received a collaborative pattern of care, indicating that integration of specialist PC into standard oncology can manifest as either segmented or concurrent care pathways. Our data suggest a closer, more dynamic and flexible collaboration between oncology and specialist PC early in the disease course of patients with advanced cancer and concurrent with active treatment.

The effect of real-time electronic monitoring of patient-reported symptoms and clinical syndromes in outpatient workflow of medical oncologists: E-MOSAIC, a multicenter cluster-randomized phase III study (SAKK 95/06).

BACKGROUND: Patients with advanced, incurable cancer receiving anticancer treatment often experience multidimensional symptoms. We hypothesize that real-time monitoring of both symptoms and clinical syndromes will improve symptom management by oncologists and patient outcomes. PATIENTS AND METHODS: In this prospective multicenter cluster-randomized phase-III trial, patients with incurable, symptomatic, solid tumors, who received new outpatient chemotherapy with palliative intention, were eligible. Immediately before the weekly oncologists' visit, patients completed the palm-based E-MOSAIC assessment (Edmonton-Symptom-Assessment-Scale, ≤3 additional symptoms, estimated nutritional intake, body weight change, Karnofsky Performance Status, medications for pain, fatigue, nutrition). A cumulative, longitudinal monitoring sheet (LoMoS) was printed immediately. Eligible experienced oncologists were defined as one cluster each and randomized to receive the immediate print-out LoMoS (intervention) or not (control). Primary analysis limited to patients having uninterrupted (>4/6 visits with same oncologist) patient-oncologist sequences was a mixed model for the difference in patients global quality of life (G-QoL; items 29/30 of EORTC-QlQ-c30) between baseline (BL) and week 6. Intention-to-treat (ITT) analysis included all eligible patients. RESULTS: In 8 centers, 82 oncologists treated 264 patients (median 66 years; overall survival intervention 6.3, control 5.4 months) with various tumors. The between-arm difference in G-QoL of 102 uninterrupted patients (intervention: 55; control: 47) was 6.8 (P = 0.11) in favor of the intervention; in a sensitivity analysis (oncologists treating ≥2 patients; 50, 39), it was 9.0 (P = 0.07). ITT analysis revealed improvement in symptoms (difference last study visit-BL: intervention -5.4 versus control 2.1, P = 0.003) and favored the intervention for communication and coping. More patients with high symptom load received immediate symptom management (chart review, nurse-patient interview) by oncologists getting the LoMoS. CONCLUSION: Monitoring of patient symptoms, clinical syndromes and their management clearly reduced patients' symptoms, but not QoL. Our results encourage the implementation of real-time monitoring in the routine workflow of oncologist with a computer solution.

A2A adenosine receptor deletion is protective in a mouse model of Tauopathy.

Consumption of caffeine, a non-selective adenosine A2A receptor (A2AR) antagonist, reduces the risk of developing Alzheimer's disease (AD) in humans and mitigates both amyloid and Tau burden in transgenic mouse models. However, the impact of selective A2AR blockade on the progressive development of AD-related lesions and associated memory impairments has not been investigated. In the present study, we removed the gene encoding A2AR from THY-Tau22 mice and analysed the subsequent effects on both pathological (Tau phosphorylation and aggregation, neuro-inflammation) and functional impairments (spatial learning and memory, hippocampal plasticity, neurotransmitter profile). We found that deleting A2ARs protect from Tau pathology-induced deficits in terms of spatial memory and hippocampal long-term depression. These effects were concomitant with a normalization of the hippocampal glutamate/gamma-amino butyric acid ratio, together with a global reduction in neuro-inflammatory markers and a decrease in Tau hyperphosphorylation. Additionally, oral therapy using a specific A2AR antagonist (MSX-3) significantly improved memory and reduced Tau hyperphosphorylation in THY-Tau22 mice. By showing that A2AR genetic or pharmacological blockade improves the pathological phenotype in a Tau transgenic mouse model, the present data highlight A2A receptors as important molecular targets to consider against AD and Tauopathies.

Assessment of anticancer-treatment outcome in patients with metastatic castration-resistant prostate cancer-going beyond PSA and imaging, a systematic literature review.

BACKGROUND: In the past years, there has been significant progress in anticancer drug development for patients with metastatic castration-resistant prostate cancer (CRPC). However, the current instruments to assess clinical treatment response have limitations and may not sufficiently reflect patient benefit. Our objective was to systematically identify tools to evaluate both patient benefit and clinical anticancer-treatment response as basis for an international consensus process and development of a specific pragmatic instrument for men with CRPC. METHODS: PubMed, Embase and CINAHL were searched to identify currently available tools to assess anticancer-treatment benefit, other than standard imaging procedures and prostate-specific antigen measurements, namely quality of life (QoL), detailed pain assessment, physical function and objective measures of other complex cancer-related syndromes in patients with CRPC. Additionally, all CRPC phase III trials published in the last 5 years were reviewed as well as studies using physical function tools in a general cancer population. The PRIMSA statement was followed for the systematic review process. RESULTS: The search generated 1096 hits, 185 full-text papers were screened and finally 73 publications were included. Additional 89 publications were included by hand-search. We identified a total of 98 tools used in CRPC trials and grouped these into three categories: 22 tools assessing QoL domains and subgroups, 47 tools for pain assessment and 29 tools for objective measures, mainly physical function and assessment of skeletal disease burden. CONCLUSION: A wide variety of assessment tools and also efforts to standardize and harmonize patient-reported outcomes and pain assessment were identified. However, the specific needs of the increasing CRPC population living longer with their incurable cancer are insufficiently captured and objective physical outcome measures are under-represented. In the age of new anticancer drug targets and principles, new methods to monitor patient relevant outcomes of antineoplastic therapy are of utmost importance.

Feasibility and acceptance of electronic monitoring of symptoms and syndromes using a handheld computer in patients with advanced cancer in daily oncology practice.

PURPOSE: We investigated the feasibility and acceptance of electronic monitoring of symptoms and syndromes in oncological outpatient clinics using a PALM (handheld computer). METHODS: The assessment of a combination of symptoms and clinical benefit parameters grouped in four pairs was tested in a pilot phase in advanced cancer patients. Based on these experiences, the software E-MOSAIC was developed, consisting of patient-reported symptoms and nutritional intake and objective assessments (weight, weight loss, performance status and medication for pain, fatigue, and cachexia). E-MOSAIC was then tested in four Swiss oncology centers. In order to compare the methods, patients completed the E-MOSAIC as a paper and a PALM version. Preferences of version and completion times were collected. Assessments were compared using Wilcoxon signed-rank tests , and the test-retest reliability was evaluated. RESULTS: The pilot phase was completed by 22 patients. Most patients and physicians perceived the assessment as useful. Sixty-two patients participated in the feasibility study. Twelve patients reported problems (understanding, optical, tactile), and five patients could not complete the assessment. The median time to complete the PALM-based assessment was 3 min. Forty-nine percent of patients preferred the PALM, 23 % preferred a paper version, and 28 % of patients had no preference. Paper vs. PALM revealed no significant differences in symptoms, but in nutritional intake (p = 0.013). Test-retest (1 h, n = 20) reliability was satisfactory (r = 073-98). CONCLUSION: Electronic symptom and clinical benefit monitoring is feasible in oncology outpatient clinics and perceived as useful by patients, oncology nurses, and oncologists. E-MOSAIC is tested in a prospective randomized trial.

Validation of the Consensus-Definition for Cancer Cachexia and evaluation of a classification model--a study based on data from an international multicentre project (EPCRC-CSA).

BACKGROUND: Weight loss limits cancer therapy, quality of life and survival. Common diagnostic criteria and a framework for a classification system for cancer cachexia were recently agreed upon by international consensus. Specific assessment domains (stores, intake, catabolism and function) were proposed. The aim of this study is to validate this diagnostic criteria (two groups: model 1) and examine a four-group (model 2) classification system regarding these domains as well as survival. PATIENTS AND METHODS: Data from an international patient sample with advanced cancer (N = 1070) were analysed. In model 1, the diagnostic criteria for cancer cachexia [weight loss/body mass index (BMI)] were used. Model 2 classified patients into four groups 0-III, according to weight loss/BMI as a framework for cachexia stages. The cachexia domains, survival and sociodemographic/medical variables were compared across models. RESULTS: Eight hundred and sixty-one patients were included. Model 1 consisted of 399 cachectic and 462 non-cachectic patients. Cachectic patients had significantly higher levels of inflammation, lower nutritional intake and performance status and shorter survival. In model 2, differences were not consistent; appetite loss did not differ between group III and IV, and performance status not between group 0 and I. Survival was shorter in group II and III compared with other groups. By adding other cachexia domains to the model, survival differences were demonstrated. CONCLUSION: The diagnostic criteria based on weight loss and BMI distinguish between cachectic and non-cachectic patients concerning all domains (intake, catabolism and function) and is associated with survival. In order to guide cachexia treatment a four-group classification model needs additional domains to discriminate between cachexia stages.

Transinguinal preperitoneal repair with the Polysoft patch: prospective evaluation of recurrence and chronic pain.

OBJECTIVE: The Polysoft patch was conceived to facilitate performance of the transinguinal preperitoneal patch method and combine the advantages of patch placement in the preperitoneal space and the open inguinal approach. The aim of this prospective study was to evaluate the rate of recurrence and chronic pain at midterm follow-up. METHODS: In a cohort of 200 hernia repairs involved in a prospective evaluation, midterm results of 171 cases operated on from 1 July 2004 to 31 December 2005 were assessed. The anesthesia was spinal in 136 (79.5%) cases, local in 26 (15.2%), and general in nine (5.3%). A questionnaire was sent to patients on 30 November 2006 asking about recurrence, chronic groin pain, and satisfaction. RESULTS: With a median follow-up of 21.9 months (11.6-29.4), 167 (97.7%) patients were evaluated, two were dead, and two were lost to follow-up. There were two (1.2%) recurrences that were reoperated on; both consisted of an indirect sac that protruded between the branches of the split patch. Eleven (6.6%) patients alleged the feeling of a foreign body, and 12 (7.2%) reported pain that occurred occasionally or upon effort but did not prevent activity. In one case, the pain present before operation was unchanged, and in three cases, the pain could clearly be attributed to an origin other than the hernia repair. No case of pain that impaired activity was observed. With regard to results, 98.2% of patients were satisfied and 97.6% declared that they would adopt the same method in case they had to be operated on for another hernia. CONCLUSION: These results suggest that the technique provides a low rate of recurrence and a low percentage of chronic pain that did not impair activity.

The Polysoft patch: prospective evaluation of feasibility, postoperative pain and recovery.

INTRODUCTION: The Polysoft patch was conceived to associate the advantages of placement of the patch in the preperitoneal space (PPS) and easiness of the inguinal incision. The aim of this study was to evaluate prospectively the feasibility and postoperative outcome of this method. METHODS: Two hundred Polysoft repairs were performed in 191 consecutive patients with Nyhus types III and IV hernias. The anesthesia was spinal in 146 patients (76.4%), local in 36 (18.8%) and general in 9 (4.7%). The patch was placed in the PPS through the hernial orifice in the fascia in direct hernias and through the internal orifice in indirect ones. The technical points and postoperative course data were prospectively recorded and postoperative pain was assessed daily by visual analogue scale (VAS) in 25 patients. RESULTS: The method was achieved in all the cases. The type of the hernias was as follows: 59 direct, 129 indirect (including 28 pantaloon and 16 sliding), 3 inguino-femoral and 9 recurrent. The size of the patch used was medium in 152 cases (76%) and large in 48 (24%). The large patch was used more in pantaloon, sliding and inguino-femoral hernias. In direct hernias the patch was not split; in indirect hernias the patch was split (so the wings recreate a new internal orifice around the spermatic cord) in 79 cases (61.2%) and not split (with the cord parietalized) in 50 cases (38.8%). The length of operation, postoperative hospital stay, return to daily activity, to work and analgesics consumption were [median +/- SD (extremes)]: 35 min +/- 9.1 (20-60), 1 day +/- 0.4 (0-5), 3 days +/- 1.8 (0-8), 15 days +/- 9.7 (1-30) and 3 days +/- 2.3 (0-10), respectively. The median number of analgesics units was 8 +/- 5.9 (0-32). The values of pain assessed daily by VAS (on 100) varied from 20.4 +/- 19.7 (0-60) at day 0, 25.0 +/- 24.5 (0-80) at day 1 to 7.5 +/- 13.7 (0-50) at day 7; the mean value for the week was 16.7 +/- 16.7 (0-57). There were 14 (7%) benign postoperative complications. CONCLUSION: This study permitted the definition of some technical points and showed that the Polysoft patch can be used for all types of hernias with a weak posterior wall, including complex cases (big scrotal, pantaloon, sliding and recurrent), with a low risk of postoperative complications, a low level of postoperative pain and a short recovery time.

Overexpression of mouse IsK protein fused to green fluorescent protein induces apoptosis of human astroglioma cells.

Intracellular K(+) plays an important role in controlling ion homeostasis for maintaining cell volume and inhibiting activity of pro-apoptotic enzymes. Cytoplasmic K(+) concentration is regulated by K(+) uptake via Na(+) -K(+) -ATPase and K(+) efflux through K(+) channels in the plasma membrane. The IsK (KCNE1) protein is known to co-assemble with KCNQ1 (KvLQT1) protein to form a K(+) channel underlying the slowly activating delayed rectifier K(+) outward current which delays voltage activation. In order to further study the activity and cellular localization of IsK protein, we constructed a C-terminal fusion of IsK with EGFP (enhanced green fluorescent protein). Expression of the fusion protein appeared as clusters located in the plasma membrane and induced degeneration of both transiently or stably transfected cells.

Controlled delivery of glial cell line-derived neurotrophic factor by a single tetracycline-inducible AAV vector.

An autoregulated tetracycline-inducible recombinant adeno-associated viral vector (rAAV-pTet(bidi)ON) utilizing the rtTAM2 reverse tetracycline transactivator (rAAV-rtTAM2) was used to conditionally express the human GDNF cDNA. Doxycycline, a tetracycline analog, induced a time- and dose-dependent release of GDNF in vitro in human glioma cells infected with rAAV-rtTAM2 serotype 2 virus. Introducing the Woodchuck hepatitis virus posttranscriptional regulatory element (WPRE) downstream to the rtTAM2 coding sequence, resulted in a more rapid induction and a higher basal expression level. In vivo, 8 weeks after a single injection of the rAAV-rtTAM2-GDNF vector encapsidated into AAV serotype 1 capsids in the rat striatum, the GDNF protein level was 60 pg/mg tissue in doxycycline-treated animals whereas in untreated animals, it was undistinguishable from the endogenous level ( approximately 4 pg/mg tissue). However, a residual GDNF expression in the uninduced animals was evidenced by a sensitive immunohistochemical staining. As compared to rAAV1-rtTAM2-GDNF, the rAAV1-rtTAM2-WPRE-GDNF vector expressed a similar concentration of GDNF in the induced state (with doxycycline) but a basal level (without doxycycline) approximately 2.5-fold higher than the endogenous striatal level. As a proof for biological activity, for both vectors, downregulation of tyrosine hydroxylase was evidenced in dopaminergic terminals of doxycycline-treated but not untreated animals. In conclusion, the rAAV1-rtTAM2 vector which expressed biologically relevant doses of GDNF in the striatum in response to doxycycline with a basal level undistinguishable from the endogenous striatal level, as measured by quantitative ELISA assay, constitutes an interesting tool for local conditional transgenesis.

Brain aging phenomena in migrating sockeye salmon Oncorhynchus nerka nerka.

Aging, a process occurring in all vertebrates, is closely related to a loss in physical and functional abilities. There is widespread interest in clarifying the relevance of environmental, metabolic, and genetic factors for vertebrate aging. In the Pacific salmon a dramatic example of aging is known. Looking for changes in the salmon brain, perhaps even in the role of initiating the aging processes, we investigated several biochemical parameters that should reflect brain functional activity and stress response such as the neurotransmitters dopamine, and serotonin, and two of their respective metabolites 3,4-dihydroxyphenylacetic acid, and 5-hydroxyindole acetic acid, as well as glutathione, glutathione disulfide, and the extent of terminal deoxynucleotidyltransferase-mediated dUTP nick end-labelling. The aging of migrating sockeye salmon (Oncorhynchus nerka nerka) is accompanied by gradual increase in dopamine and serotonin turnover and a gradual decrease of brain total protein and glutathione levels. There appears to be an increased need for detoxification of reactive biological intermediates since activities of superoxide dismutase and catalase increase with age. However, our data do not support a major increase in apoptotic cell death during late aging but rather implicate an age related downward regulation of protein and glutathione synthesis and proteolysis increasing the need for autophagocytosis or heterophagocytosis in the course of cell death.

ATP synthase motor components: proposal and animation of two dynamic models for stator function.

Recent research indicates that ATP synthases (F(0)F(1)) contain two distinct nanomotors, one an electrochemically driven proton motor contained within F(0) that drives an ATP hydrolysis-driven motor (F(1)) in reverse during ATP synthesis. This is depicted in recent models as involving a series of events in which each of the three alphabeta pairs comprising F(1) is induced via a centrally rotating subunit (gamma) to undergo the sequential binding changes necessary to synthesize ATP (binding change mechanism). Stabilization of this rotary process (i.e., to minimize "wobble" of F(1)) is provided in current models by a peripheral stalk or "stator" that has recently been shown to extend from near the bottom of the ATP synthase molecule to the very top of F(1). Although quite elegant, these models envision the stator as fixed during ATP synthesis, i.e., bound to only a single alphabeta pair. This is despite the fact that the binding change mechanism views each alphabeta pair as going through the same sequential order of conformational changes which demonstrate a chemical equivalency among them. For this reason, we propose here two different dynamic models for stator function during ATP synthesis. Both models have been designed to maintain chemical equivalency among the three alphabeta pairs during ATP synthesis and both have been animated.

Inguinal hernia: a patch covering only the myopectineal orifice is effective.

A large mesh in the preperitoneal space, spread on iliac vessels and bladder, can cause future difficulties in a case of urogenital or vascular disease. Since all recurrences are located in the area of the myopectineal orifice, a mesh covering only this area, as in the Rives procedure, is effective and avoids these drawbacks. However, the Rives procedure is demanding, which is why we tried to simplify the technique. A mesh 8-10 cm long and 6-7 cm wide was spread in the preperitoneal space using the inguinal approach, without any fixation or with only a few stitches; the fascia was then simply approximated over the mesh without tension. A total of 161 hernias (99% Nyhus type III and IV) were repaired using this technique. Only six benign complications (3.7%) occurred. With a median follow-up of 63 months (range, 18-94 months), only one recurrence occurred (0.7%), due to misplacement of the mesh, eight patients complained of mild pain, and no late complications were observed. In conclusion, placement of a small mesh covering only the myopectineal orifice using the inguinal approach is effective and is associated with a low risk of drawbacks and complications.

6-hydroxydopamine-induced nuclear factor-kappa B activation in PC12 cells.

The involvement of nuclear Factor-kappa B (NF-kappa B) transcription factor in PC12 cell death triggered by the dopaminergic neurotoxin 6-hydroxydopamine (6-OHDA) was investigated. Results show that oxidative stress generated by 6-OHDA activates NF-kappa B. When the NF-kappa B activation was inhibited by parthenolide, PC12 cell death induced by 6-OHDA was significantly increased, thus suggesting an involvement of this transcription factor in a protective mechanism against 6-OHDA toxicity. To further assess this hypothesis, we studied the involvement of NF-kappa B in the protective effect of two anti-apoptotic genes, bcl-2 and bfl-1. Although Bcl-2 and Bfl-1 expression normally protects PC12 cells from 6-OHDA, parthenolide strongly decreased the beneficial effects afforded by transgene expression. These results suggest: (1) that the transcription factor NF-kappa B is likely associated with the protection of catecholaminergic PC12 cells and (2) that the protective effects afforded by bcl-2 and bfl-1 expression may be dependent on NF-kappa activation.

[Tension-free procedures: progress in the treatment of inguinal hernia]. / Les procédés sans tension: un progrès dans le traitement de la hernie inguinale.

OBJECTIVE: Tension-free procedures are aimed to minimize post-operative pain and rate of recurrence, by replacing sutures under tension by a mesh without any approximation of the margins of the hernial orifice. Moreover they offer the advantage of being performed under local or epidural anesthesia. The aim of this study was to verify, by a prospective multicentre evaluation, if the results attributed to these procedures are obtained in current practice. RESULTS: Evaluation involved 435 hernias, treated by Lichtenstein procedure, Gilbert plug and Perfix plug. There were 19 postoperative benign complications (4.4%). The durations of analgesics consumption, post-operative hospital stay, cessation of normal activities and time off work [mean, [(SD), (extremes)]] were 3.3 days [(3.9) (0-60)], 1.3 days [(1.1) (0-16)], 4.5 days [(3.1) (0-34)] and 15.4 days [(10.2) (0.60)] respectively. With a mean follow-up of 36 months [(14) (6-67)], 423 hernias (97.2%) were assessed. Two (0.5%) recurrences occurred. Twenty three patients had secondary troubles (5.8%): 21 patients complained of chronic pain, one had atrophy of the testis and one plug had to be removed. CONCLUSION: Our results confirm that tension-free procedures are minimally invasive, induce few benign postoperative complications, low pain and allow early return to normal activity.

Epilepsy surgery: chance for a cure.

Epilepsy is a chronic disorder with medical, as well as psychosocial, consequences. Many patients with epilepsy are well controlled by medication and are able to tolerate the side effects of the antiepileptic drugs needed to control their disorder. However, there are many people who are either unable to gain seizure freedom with medications or are intolerant of the side effects of their drugs. In some of these patients, particularly those with mesial temporal sclerosis, surgery offers a viable treatment alternative and a chance for a cure rather than just lifelong management.

Attitudes and practices of U.S. oncologists regarding euthanasia and physician-assisted suicide.

BACKGROUND: The practices of euthanasia and physician-assisted suicide remain controversial. OBJECTIVE: To achieve better understanding of attitudes and practices regarding euthanasia and physician-assisted suicide in the context of end-of-life care. DESIGN: Cohort study. SETTING: United States. PARTICIPANTS: 3299 oncologists who are members of the American Society of Clinical Oncology. MEASUREMENTS: Responses to survey questions on attitudes toward euthanasia and physician-assisted suicide for a terminally ill patient with prostate cancer who has unremitting pain, requests for and performance of euthanasia and physician-assisted suicide, and sociodemographic characteristics. RESULTS: Of U.S. oncologists surveyed, 22.5% supported the use of physician-assisted suicide for a terminally ill patient with unremitting pain and 6.5% supported euthanasia. Oncologists who were reluctant to increase the dose of intravenous morphine for terminally ill patients in excruciating pain (odds ratio [OR], 0.61 [95% CI, 0.48 to 0.77]) and had sufficient time to talk to dying patients about end-of-life care issues (OR, 0.79 [CI, 0.71 to 0.87]) were less likely to support euthanasia or physician-assisted suicide. During their career, 3.7% of surveyed oncologists had performed euthanasia and 10.8% had performed physician-assisted suicide. Oncologists who were reluctant to increase the morphine dose for patients in excruciating pain (OR, 0.58 [CI, 0.43 to 0.79]) and those who believed that they had received adequate training in end-of-life care (OR, 0.86 [CI, 0.79 to 0.95]) were less likely to have performed euthanasia or physician-assisted suicide. Oncologists who reported not being able to obtain all the care that a dying patient needed were more likely to have performed euthanasia (P = 0.001). CONCLUSIONS: Requests for euthanasia and physician-assisted suicide are likely to decrease as training in end-of-life care improves and the ability of physicians to provide this care to their patients is enhanced.