Management of chronic neuropathic pain with methadone: a review of 13 cases

The synthetic opioid methadone has generated much interest in recent years among clinicians involved in the management of intractable chronic cancer pain. Its use as an analgesic is starting to extend to the treatment of noncancer pain, particularly neuropathic pain. Unfortunately, the evidence for its use in the management of neuropathic pain is limited to a few case studies. We examined retrospectively during a 12-month study period the clinical response of all 13 patients at our pain clinic who were prescribed methadone in an attempt to control neuropathic pain resistant to conventional analgesics. A questionnaire was also administered to the 9 patients who continued to take methadone at 12 months posttreatment. A total of 4 patients (31%) discontinued it by the end of the 12-month study period. Patients discontinued methadone due to the absence of pain relief and due to various intractable, undesirable side effects. Somnolence was the most common adverse effect reported, followed by nausea, constipation, and vomiting. All patients took coanalgesics (eg, amitriptyline, gabapentin) or other analgesics (eg, morphine, nonsteroidal anti-inflammatory drugs) during methadone treatment to control pain. The 9 patients who continued to take methadone at 12 months reported experiencing on average 43% pain relief (range 0-80%), 47% improvement in quality of life (range 0-100%), and 30% improvement in quality of sleep (range 0-60%). Methadone was effective at relieving pain and ameliorating quality of life and sleep in 62% of patients. These findings suggest that methadone can offer an acceptable success rate for the treatment of neuropathic pain. Prospective randomized, placebo-controlled studies are now needed to examine more rigorously the benefits of methadone for this type of pain.     

Ultimate journey of the terminally ill: Ways and pathways of hope

ObjectiveTo better understand the role of hope among terminally ill cancer patients.DesignQualitative analysis.SettingA tertiary specialized cancer centre in Canada.ParticipantsCancer patients in palliative care with an estimated remaining life expectancy of 12 months or less (N = 12) and their loved ones (N = 12) and treating physicians (N = 12).MethodsEach patient underwent up to 3 interviews and identified a loved one who participated in 1 interview. Treating physicians were also interviewed. All interviews were fully transcribed and analyzed by at least 2 investigators. Interviews were collected until saturation occurred.ConclusionApproaches aimed at sustaining hope need to reflect that patients’ reactions might fluctuate between despair and a form of acceptance that leads to a certain serenity. Clinicians need to maintain some degree of hope while remaining as realistic as possible. The findings also raise questions about how hope influences patients’ perceptions and acceptance of their treatments.     

Trends in Nontherapeutic Laparotomy Rates in Patients Undergoing Surgical Therapy for Hepatic Colorectal Metastases

Surgery is the treatment of choice in selected patients with hepatic colorectal metastases. Despite improvements in preoperative imaging, patients can undergo unnecessary nontherapeutic laparotomy. The aim of this study was to examine trends in nontherapeutic laparotomy rates in patients undergoing planned surgical therapy for hepatic colorectal metastases. Data from 530 operations (461 patients) undergoing potentially curative surgical therapy for colorectal liver metastases between 1994 and 2005 were analyzed. The incidence of nontherapeutic laparotomy was determined and factors associated with nontherapeutic laparotomy were identified. Overall, 49 nontherapeutic laparotomies were performed (9.2%). Higher nontherapeutic laparotomy rates were seen in patients with multiple metastases and tumor size >5 cm (both P < 0.05). Preoperative positron emission tomography (PET) imaging was associated with lower risk of nontherapeutic laparotomy [5.6% versus 12.4%, P = 0.009, odds ratio (OR) = 0.42]. At laparotomy, extrahepatic findings were the reason for nontherapeutic laparotomy in 44.9% of cases. The nontherapeutic laparotomy rate significantly decreased over time (14.9% for 1994–1997 versus 9.6% for 1998–2001 versus 4.7% for 2002–2005; P = 0.003). While patients in each time period were similar with regard to tumor specific factors, utilization of PET imaging (P < 0.001) as well as resection plus ablation (P = 0.004) increased over time. We conclude that prevalence of nontherapeutic laparotomy for patients undergoing surgical exploration for hepatic colorectal metastases has decreased significantly in recent years to less than 5%. The reasons for this trend are probably multifactorial and may include improved preoperative assessment, such as PET imaging, as well as salvage surgical options.     

Specificity of the anti-glycolytic activity of 3-bromopyruvate confirmed by FDG uptake in a rat model of breast cancer

Summary   Purpose: To evaluate the anti-glycolytic effects of 3-BrPA on rats bearing RMT mammary tumors, by determining FDG uptake after intravenous administration of the therapeutic dose. Materials and Methods: Sixteen rats bearing RMT tumors were treated either with 15 mM 3-BrPA in 2.5 ml of PBS or with 2.5 ml of PBS. After treatment, all rats received FDG and were sacrificed 1 h later. Results: 3-BrPA treatment significantly decreased FDG uptake in tumors by 77% (p = 0.002). FDG uptake did not significantly decrease in normal tissues after treatment. Conclusion: Our study showed that 3-BrPA exhibits a strong anti-glycolytic effect on RMT cells implanted in rats. Buijs and Vossen contributed equally to this work.     

Validity of the Actical accelerometer step-count function

PURPOSE: To assess the validity of the new Actical accelerometer step count function. METHODS: Actical step counts were compared according to two criterion standards. 1) Eight Acticals were assessed using a mechanical shaker table under six different testing conditions. 2) Thirty-eight volunteers (aged 9-59 yr) wore eight Acticals and eight Actigraphs during treadmill walking (50 and 83 m.min(-1)) and running (133 m.min(-1)) for 6 min at each speed. Steps were counted during the second and fourth minutes of each speed by a trained observer. RESULTS: The correlation between Actical step counts and the mechanical shaker step counts was excellent (r = 1.0). Compared with visually counted steps, both the Actical and Actigraph step counts were significantly different at 50 m.min(-1); however, no significant differences were evident at 83 and 133 m.min(-1). The criterion-related validity correlations (r) for the Actical and Actigraph, respectively, were 0.73 and 0.52 at the slow walk condition and 0.99 and 0.99 at the normal walk and run conditions. CONCLUSION: The new step count function of the Actical accelerometer provides valid estimates of step counts at 83 and 133 m.min(-1) on a range of healthy participants.     

Early relapse in ALL is identified by time to leukemia in NOD/SCID mice and is characterized by a gene signature involving survival pathways

We investigated the engraftment properties and impact on patient outcome of 50 pediatric acute lymphoblastic leukemia (ALL) samples transplanted into NOD/SCID mice. Time to leukemia (TTL) was determined for each patient sample engrafted as weeks from transplant to overt leukemia. Short TTL was strongly associated with high risk for early relapse, identifying an independent prognostic factor. This high-risk phenotype is reflected by a gene signature that upon validation in an independent patient cohort (n?= 197) identified a high-risk cluster of patients with early relapse. Furthermore, the signature points to independent pathways, including mTOR, involved in cell growth and apoptosis. The pathways identified can directly be targeted, thereby offering additional treatment approaches for these high-risk patients.     

Evaluation of image-guidance protocols in the treatment of head and neck cancers

PURPOSE: The aim of this study was to assess the residual setup error of different image-guidance (IG) protocols in the alignment of patients with head and neck cancer. The protocols differ in the percentage of treatment fractions that are associated with image guidance. Using data from patients who were treated with daily IG, the residual setup errors for several different protocols are retrospectively calculated. METHODS AND MATERIALS: Alignment data from 24 patients (802 fractions) treated with daily IG on a helical tomotherapy unit were analyzed. The difference between the daily setup correction and the setup correction that would have been made according to a specific protocol was used to calculate the residual setup errors for each protocol. RESULTS: The different protocols are generally effective in reducing systematic setup errors. Random setup errors are generally not reduced for fractions that are not image guided. As a consequence, if every other treatment is image guided, still about 11% of all treatments (IG and not IG) are subject to three-dimensional setup errors of at least 5 mm. This frequency increases to about 29% if setup errors >3 mm are scored. For various protocols that require 15% to 31% of the treatments to be image guided, from 50% to 60% and from 26% to 31% of all fractions are subject to setup errors >3 mm and >5 mm, respectively. CONCLUSION: Residual setup errors reduce with increasing frequency of IG during the course of external-beam radiotherapy for head-and-neck cancer patients. The inability to reduce random setup errors for fractions that are not image guided results in notable residual setup errors.     

Valproic acid induces non-apoptotic cell death mechanisms in multiple myeloma cell lines

Multiple myeloma (MM) is an incurable hematological disorder characterized by dysregulated proliferation of terminally differentiated plasma cells. Aberrant histone acetylation has been observed in the development of numerous malignancies. Histone deacetylase inhibitors such as valproic acid (VPA) are promising drugs for cancer therapy since they have been reported to have antiproliferative effects and to induce differentiation in carcinoma and leukemic cells. Considering the advantage of being already in clinical use for epilepsy treatment, valproic acid might be a promising therapeutic candidate drug in the management of multiple myeloma. In this study, we show that the short fatty acid VPA has a time and dose-dependent cytotoxic effect on the MM cell lines OPM2, RPMI and U266. The influence of VPA on cell cycle and apoptosis have been evaluated by flow cytometry. Our results show that the three cell lines are blocked in G0/G1 phase. The observed sensitivity to VPA can be partially explained by late apoptosis. Since caspase 3 is activated in all tested cell lines after VPA treatment, a caspase-dependent pathway seems to be involved but not activated by the classic apoptotic pathways. We have also studied another mechanism of cell death, the senescence-like phenotype, but did not find any evidence for its implication. Thus, treatment with VPA may imply other alternative cell death mechanisms.     

Phase-contrast magnetic resonance angiography measurements of global cerebral blood flow in the neonate

Cerebral blood flow (CBF) alterations are important in pathogenesis of neonatal ischemic/hemorrhagic brain damage. In clinical practice, estimation of neonatal CBF is mostly based on Doppler-measured blood flow velocities in major intracranial arteries. Using phase-contrast magnetic resonance angiography (PC-MRA), global CBF can be estimated, but there is limited neonatal experience. The objective of this study was to gain experience with PC-MRA for the determination of global CBF in neonates. In infants eligible for MRI, PC-MRA global CBF was determined by measuring volume blood flow in both internal carotid arteries (ICAs) and basilar artery (BA). Thirty newborns (GA, 25.7-42.1 wk; weight, 1050-5858 g; postconceptional age, 225-369 d) were investigated. Total PC-MRA CBF ranged from 27 to 186 mL/min. Significant correlations between PC-MRA CBF and postconceptional age and weight were detected. When calculating PC-MRA measured CBF per kilogram body weight, brain perfusion was about stable over the range of postconceptional ages and ranged between 11 and 48 mL/min/kg (median, 25 mL/min/kg). In conclusion, neonatal PC-MRA CBF seems to be a useful technique to estimate noninvasive CBF.