When the treatment goal is not cure: are cancer patients equipped to make informed decisions?

PURPOSE: Informed decision making now is considered the underpinning of ethical medical practice. We aimed to determine the extent to which patients with incurable cancer are adequately informed of their prognosis and treatment options and encouraged to participate in treatment decisions. PATIENTS AND METHODS: One hundred eighteen cancer patients with incurable disease presenting for an initial consultation with one of nine oncologists at two Sydney tertiary referral hospitals participated in the study. Consultations were recorded on audiotape to permit a content analysis of doctor-patient interactions. We devised a coding system to assess disclosure of information and to evaluate doctor encouragement of patient participation in treatment decision making. Patient recall, satisfaction, anxiety, and perceptions of the decision-making process were assessed to determine the effects of informed decision making on patient outcomes. RESULTS: Most patients were informed about the aim of anticancer treatment (84.7%), that their disease was incurable (74.6%), and about life expectancy (57.6%). An alternative to anticancer treatments was presented to 44.1%, 36.4% were informed about how anticancer treatment would affect quality of life, and 29.7% were offered a management choice. Oncologists checked patient understanding in only 10.2% of consultations. Although greater information disclosure did not seem to elevate anxiety levels, greater patient participation in the decision-making process was associated with increased anxiety levels (P =.0005), which persisted over a 2-week time span. CONCLUSION: Most patients were well informed, but important gaps remain, especially concerning information about prognosis and alternatives to anticancer treatment. These gaps invite the question concerning whether patients are led toward anticancer treatment.     

Effect of verapamil on submissive behavior in genetically bred hypercholinergic rats in a water competition test

Male hypercholinergic FSL (Flinders Sensitive Line) and control FRL (Flinders Resistant Line) rats were placed on a water deprivation schedule and tested for dominance behavior with FSL/FRL pairs competing for water. FSL rats spent significantly less time drinking than their FRL partners. Acute injection of 10 mg/kg of verapamil, a calcium channel inhibitor, to FSL rats markedly increased their drinking time without influencing water intake in individually tested rats. This effect of the drug was no longer seen after prolonged 4 day treatment. It is suggested that submissiveness of FSL animals in the water competition test might be due to increased fear which is alleviated by verapamil treatment. Tolerance seems to develop to this effect of the drug.     

Recent advances in conventional-dose salvage chemotherapy in patients with cisplatin-resistant or refractory testicular germ cell tumors

Testicular germ cell tumors represent the most frequent malignancy in young males aged 20-35 years. Despite the considerably high cure rates provided by platinum-based chemotherapy, 20-30% of cases with advanced disease do not achieve a long-term disease-free survival with first-line chemotherapy. These patients are candidates for conventional-dose or high-dose salvage chemotherapy. The current conventional-dose salvage regimens of reference are the vinblastine-ifosfamide-cisplatin or etoposide-ifosfamide-cisplatin combinations, which are expected to cure approximately 25% of non-seminomatous germ-cell tumour patients. Paclitaxel has also been proved effective both as monotherapy in heavily-pretreated cases and as part of first-line salvage regimens; the combination of paclitaxel-ifosfamide-cisplatin, followed or not by high-dose chemotherapy, induced a favorable long-term disease-free survival rate, especially in patients with good prognosis. Newer cytotoxic drugs, such as gemcitabine and oxaliplatin have also been proved effective, while other agents, such as temozolamide, or targeted therapies, such as trastuzumab in cases over-expressing HER2/neu (20% of relapsing germ-cell tumors) are currently under evaluation. Seminomas have generally a better prognosis than non-seminomatous tumors and salvage therapy is expected to cure about 50% of all cases.     

Aneurysms of the carotid artery

Carotid artery aneurysms are an uncommon but important problem. The available data suggests that, untreated, these aneurysms lead to neurologic symptoms from embolization. Pseudoaneurysms of the carotid artery result from injury or may be the long-term sequelae of a spontaneous carotid dissection. While open surgery has been the primary mode of treatment, these aneurysms are being treated more commonly with endovascular approaches. This trend is partly the result of the increasing experience with the endovascular treatment of carotid artery stenosis. The endovascular approach offers advantages in other situations where open access to the distal extent of the aneurysm is difficult or neck radiation leads to concerns about wound healing. This article outlines the etiology, new diagnostic modalities, and treatment of aneurysms of the carotid artery.     

Development and localisation of GABA(A) receptor alpha1, alpha2, beta2 and gamma2 subunit mRNA in the chick optic tectum

An in situ hybridisation technique was used to analyse the spatial and temporal pattern of expression of the mRNA encoding the four gamma-aminobutyric acid A (GABA(A)) receptor subunits (alpha1, alpha2, beta2, and gamma2) in the developing chick optic tectum. As a rule, layer i, layer h, and transient cell compartment 3 (TCC3) show the highest levels of expression, especially of alpha1, alpha2 and beta2, which undergo striking changes as a function of time. Apart from these common features, the global pattern is highly complex and dynamic. Such complexity derives from the fact that each subunit exhibits a characteristically distinct pattern of expression and the temporal evolution of each differs in the different layers of the tectum. The influence of several developmental cell behaviours such as proliferation, neuronal migration, programmed cell death, and differentiation must be taken into account to understand pattern complexity and dynamics. Our results suggest that differences in the rate of subunit expression, particularly of alpha1, alpha2, and beta2, could have significant consequences on GABA(A) receptor complex subunit composition along development and on the functional properties of the GABA neurotransmitter system.     

Oxaliplatin plus high-dose leucovorin and 5-fluorouracil (FOLFOX 4) in platinum-resistant and taxane-pretreated ovarian cancer: a phase II study

OBJECTIVE: A prospective phase II study was conducted to evaluate the efficacy and toxicity of oxaliplatin plus 5-fluoruracil (5-FU) and high-dose leucovorin (LV) (FOLFOX-4) in patients with platinum-resistant, taxane-pretreated recurrent ovarian cancer. PATIENTS AND METHODS: Thirty-eight patients, with a median age of 58 years (range 33-77), were treated with oxaliplatin 85 mg m(-2) as a 2-h infusion on day 1, LV 200 mg m(-2) day(-1) as a 2-h infusion followed by bolus 5-FU 400 mg m(-2) day(-1) and a 22-h infusion of 5-FU 600 mg m(-2) day(-1) for 2 consecutive days. Treatment was repeated every 3 weeks. Patients were evaluated for response every two cycles. RESULTS: The vast majority of patients had performance status 0 or 1 and 76.3% had > or = 2 metastatic sites. A median number of four cycles per patient (range, 1-8) were administered. Based on an intention-to-treat analysis, 3 patients (7.9%) achieved a complete response (CR) and 8 (21.1%) achieved a partial response (PR), for an overall response rate of 29%. Another 29% of patients had stable disease (SD). The median relapse-free survival was 5.2 months (range 2.5-17), the median time to tumor progression was 4.8 months (range 0.6-19), and the median overall survival was 10.1 months (range 0.2-36). Toxicity was mild to moderate. Grade 3/4 neutropenia and thrombocytopenia occurred in 29% and 21.1% of patients, respectively. Febrile neutropenia was encountered in 3 patients (7.9%), who were successfully treated. Grade 3/4 neurotoxicity developed in 15.8% of patients; neurotoxicity gradually declined after treatment discontinuation. Alopecia, nausea-vomiting, diarrhea, mucositis, and asthenia were not a serious problem. There were no treatment-related deaths. CONCLUSION: The combination of oxaliplatin and 5-FU/LV (FOLFOX-4) appears to be an effective regimen with a good toxicity profile for the treatment of platinum-resistant, taxane-pretreated ovarian cancer.     

Proving the value of simulation in laparoscopic surgery

OBJECTIVE: To assess the McGill Inanimate System for Training and Evaluation of Laparoscopic Skills (MISTELS) physical laparoscopic simulator for construct and predictive validity and for its educational utility. SUMMARY BACKGROUND DATA: MISTELS is the physical simulator incorporated by the Society of American Gastrointestinal and Endoscopic Surgeons (SAGES) in their Fundamentals of Laparoscopic Surgery (FLS) program. MISTELS' metrics have been shown to have high interrater and test-retest reliability and to correlate with skill in animal surgery. METHODS: Over 200 surgeons and trainees from 5 countries were assessed using MISTELS in a series of experiments to assess the validity of the system and to evaluate whether practicing MISTELS basic skills (transferring) would result in skill acquisition transferable to complex laparoscopic tasks (suturing). RESULTS: Face validity was confirmed through questioning 44 experienced laparoscopic surgeons using global rating scales. MISTELS scores increased progressively with increasing laparoscopic experience (n = 215, P < 0.0001), and residents followed over time improved their scores (n = 24, P < 0.0001), evidence of construct validity. Results in the host institution did not differ from 5 beta sites (n = 215, external validity). MISTELS scores correlated with a highly reliable validated intraoperative rating of technical skill during laparoscopic cholecystectomy (n = 19, r = 0.81, P < 0.0004; concurrent validity). Novice laparoscopists were randomized to practice/no practice of the transfer drill for 4 weeks. Improvement in intracorporeal suturing skill was significantly related to practice but not to baseline ability, career goals, or gender (P < 0.001). CONCLUSION: MISTELS is a practical and inexpensive inanimate system developed to teach and measure technical skills in laparoscopy. This system is reliable, valid, and a useful educational tool.