Radiotherapy in prostate cancer treatment

Prostate cancer is a complex disease, with many controversial aspects of management in almost all stages of disease. The natural history of this tumor is variable and is influenced by multiple prognostic factors. Radical prostatectomy and radiotherapy are standard treatment options for disease limited to the prostate. The data in literature does not provide clear- cut evidence for the superiority of any treatment. Neo- adjuvant or adjuvant hormonal therapy improves local control and survival in locally advanced disease. The patients treated with radiotherapy would have a relatively long life expectancy, not great risk factors for radiation toxicity and a preference for radiotherapy. The advantages of radiotherapy are that it has a significant potential for cure, it is well tolerated in the majority of men especially when the modern techniques of conformal radiotherapy and intensity modulated therapy are used and it is non-invasive therapeutic options with no anesthesia risk. Expected complications like radiation cystitis, impotence and proctitis are registered in about 1% of patients.     

The features of myasthenia gravis with autoantibodies to MuSK

OBJECTIVES: To determine if myasthenia gravis (MG) with antibodies to MuSK is a distinct subgroup of seronegative MG. METHODS: We assayed antibodies to muscle specific tyrosine kinase (MuSK) in 55 MG patients who had no antibodies to acetylcholine receptors and looked for the specific phenotype, comparing clinical features of anti-MuSK positive and anti-MuSK negative MG patients. RESULTS: MG with anti-MuSK antibodies was characterised by a striking prevalence of female patients (15 women, two men). Age at onset ranged from 22 to 52 years, with 70.6% of patients presenting at < 40 years of age. The majority of patients (82.4%) had prevalent involvement of facial and bulbar muscles. One third of them did not respond well to anticholinesterase drugs. Steroid immunosuppression was effective in eight patients (44.4%). Nine patients underwent thymectomy; six of these had no thymus pathology, while three had a hyperplastic thymus. At the end of the observation period, six (35.3%) patients were in remission, five (29.4%) improved, four (23.6%) did not change, and two (11.7%) had died. CONCLUSIONS: MG patients with antibodies to MuSK have characteristic clinical features that are different from features of the remaining seronegative MG patients. This emphasises the predictive value of anti-MuSK antibody analysis in seronegative MG patients.     

Epidemiology of myotonic dystrophy type 1 in the population of central Serbia

The objective of this epidemiological survey was to estimate the frequency and distribution of Myotonic dystrophy type 1 (MD1) (Steinert's disease) in central Serbia, during the period 1983-2002. The data on the number of diagnosed MD1 patients were obtained using the analysis of hospital records, which were examined in all the relevant neurological institutions in central Serbia in the mentioned period. Incidence rate and prevalence were used for the data analysis. In the study period in central Serbia, 154 patients (78 males and 76 females) with MD1 were identified. The average annual incidence rate of MD1 was 1.3 (95% CI-confidence interval 0.1-7.2) per 1,000,000 population, 1.4/1,000,000 (95% CI 0.1-7.2) for males, 1.3/1,000,000 (95% CI 0.1-7.2) for females. The trend of MD1 incidence rates in the observed period in central Serbia had a tendency of the statistically significant decrease, according to the linear model, in both male (y = 0.205 - 0.0066x, p = 0.021) and female populations (y = 0.1788 - 0.0048x, p = 0.032). The prevalence of MD1 on December 31, 2002 in central Serbia was 3.8/100,000 (95% IP 3.2-4.6), 3.7/100,000 (95% IP 3.3 - 4.8) for males, 3.3/100,000 (95% IP 3.0 - 4.4) for females.     

Anti-glutamic acid decarboxylase antibodies in the serum and cerebrospinal fluid of patients with stiff-person syndrome: correlation with clinical severity

BACKGROUND: Stiff-person syndrome (SPS) is an immune-mediated central nervous system disorder characterized by fluctuating muscle stiffness, disabling spasms, and heightened sensitivity to external stimuli. Up to 80% of patients with SPS have anti-glutamic acid decarboxylase (GAD) antibodies in the serum or cerebral spinal fluid (CSF). Whether these antibodies are clinically relevant and correlate with disease severity is unknown. OBJECTIVE: To correlate anti-GAD antibody titers in the serum and CSF of patients with SPS with the degree of clinical severity. DESIGN: Patients studied the last 6 years. SETTING: The Clinical Center of the National Institutes of Health, Bethesda, MD. PATIENTS: Sixteen patients with typical SPS and elevated serum anti-GAD antibody titers. INTERVENTIONS: Antibody titers in serum and CSF were measured by radioimmunoassay, and the intrathecal anti-GAD-specific IgG production was calculated. MAIN OUTCOME MEASURES: Comparison of antibody titers with stiffness index and heightened sensitivity scores based on scales that reliably measure disease severity. RESULTS: The mean disease duration was 11 years (range, 5-30 years). The mean anti-GAD antibody titer in the serum was 51 500 U/mL (range, 24 000-200 000 U/mL); and in the CSF, 181 U/mL (range, 30-400 U/mL). A 10-fold increased intrathecal production of GAD-specific IgG antibodies was noted. No correlation was found between antibody titers in serum or CSF with disease severity. In 4 patients, the anti-GAD antibody titers measured serially during a 2-year period did not correlate with clinical fluctuations. CONCLUSIONS: In patients with SPS, the anti-GAD antibody titers in serum and CSF do not correlate with disease severity or duration. Anti-GAD antibodies are an excellent marker for SPS, but monitoring their titers during the course of the disease may not be of practical value.     

Expression of A20 in the vessel wall of rat-kidney allografts correlates with protection from transplant arteriosclerosis

BACKGROUND: Chronic rejection with development of transplant arteriosclerosis is the major culprit involved in loss of kidney allografts. The allografts' fate was thought to depend on the intensity of the host immune responses and the potency of immunosuppressive regimens. Recent data suggests that grafts contribute to their own survival by way of up-regulation of "cytoprotective" genes. METHODS: We analyzed the expression of four cytoprotective genes, A20, Bcl-2, Bcl-x(L) and heme oxygenase (HO)-1, in three rat renal allograft models of chronic rejection: Fisher 344-Lewis (F344/Lew), Dark Agouti-Brown Norway (DA/BN), and DA-Wistar-Furth (WF). We chose these genes for their known anti-inflammatory and anti-apoptotic function in endothelial cells (EC) and the atheroprotective function of A20 in smooth muscle cells (SMC). RESULTS: Twenty-eight and 9 weeks following transplantation, F344/Lew and DA/BN transplants had stable graft function. Histopathologic analysis showed moderate tissue damage, minimal cellular infiltrates, and preserved vascular integrity correlating with high expression of A20 in SMC. Conversely, impaired allograft function in the DA/WF combination with substantial transplant arteriosclerosis was noted in 60% of the grafts correlating with absent or decreased A20 expression in EC and SMC. In all combinations, expression of HO-1, Bcl-2, and Bcl-x(L) colocalized with infiltrating cells and was not informative on the graft status. CONCLUSIONS: We demonstrate for the first time a strict correlation between A20 expression in the vessel and the absence of transplant arteriosclerosis in rat kidney-allograft models. This data is similar to data obtained in human kidney allografts and suggests that A20 may represent a novel therapeutic target for the prevention of chronic allograft rejection.     

Stimulation methods for neuropathic pain control

Neurostimulation methods for control of chronic neuropathic pain have recently gained in popularity. The reasons for this are mutifactorial. As opposed to nerve ablation, these methods are minimally invasive and reversible. The improvements in hardware design simplified implantation techniques and prolonged equipment longevity. Stimulation trials have become less invasive, allowing patients to test its effects before final implantation. Finally, the scientific evidence has shown good outcomes of neurostimulation methods for chronic neuropathic pain control. Recent research efforts have revealed new potential mechanisms of action of neurostimulation. Whereas its action was widely explained by gate control theory in the past, it seems that neuromodulation acts also by modulation of neurotransmitters in the central nervous system. Three neurostimulation methods are currently used in clinical practice: spinal cord stimulation (SCS), peripheral nerve stimulation (PNS), and deep brain stimulation (DBS). The SCS and PNS are excellent treatment choices for certain forms of neuropathic pain. The new indications for SCS are end-stage peripheral vascular disease and ischemic heart disease, whereas PNS is used for the treatment of occipital neuralgia and chronic pelvic pain. DBS is reserved for carefully selected patients in whom the other treatment modalities have failed. In a minority of patients the "tolerance" to neurostimulation develops after long-term use. Further research is needed to establish better outcome predictors to neurostimulation and possibly improve patient selection criteria.     

200 Hz flying-spot technology of the LaserSight LSX excimer laser in the treatment of myopic astigmatism: six and 12 month outcomes of laser in situ keratomileusis and photorefractive keratectomy

PURPOSE: To evaluate safety, efficacy, predictability, and stability in the treatment of myopic astigmatism with laser in situ keratomileusis (LASIK) and photorefractive keratectomy (PRK) using the 200 Hz flying-spot technology of the LaserSight LSX excimer laser. SETTING: SynsLaser Clinic, Troms?, Norway. METHODS: This retrospective study included 110 eyes treated with LASIK and 87 eyes treated with PRK that were available for evaluation at 6 and 12 months, respectively. The mean preoperative spherical equivalent (SE) was -5.35 diopters (D) +/- 2.50 (SD) (range -1.13 to -11.88 D) in the LASIK eyes and -4.72 +/- 2.82 D (range -1.00 to -15.50 D) in the PRK eyes. The treated cylinder was 4.00 D in both groups. Eleven (8.5%) LASIK eyes and 8 (7.4%) PRK eyes had secondary surgical procedures before 6 and 12 months, respectively, and were excluded when the 6 and 12 month outcomes were analyzed. RESULTS: None of the eyes lost 2 or more lines of best spectacle-corrected visual acuity. Seventy-seven percent of the LASIK eyes and 78% of the PRK eyes achieved an uncorrected visual acuity of 20/20 or better; 98% in both groups achieved 20/40 or better. The SE was within +/-0.5 D of the desired refraction in 83% of the LASIK eyes and 77% of the PRK eyes; it was within +/-1.0 D in 97% and 98%, respectively. The cylinder correction had a mean magnitude of error of 0.04 +/- 0.31 D (range -0.96 to +0.85 D) in the LASIK eyes and 0.02 +/- 0.37 D (range -1.44 to +0.72 D) in the PRK eyes. Refractive stability was achieved at 1 month and beyond in the LASIK eyes and at 3 months and beyond in the PRK eyes. CONCLUSION: The outcomes of this study are comparable to those achieved with lasers that use small-beam technology with a lower frequency, as well as with other types of delivery systems. They suggest that the 200 Hz technology used in the LaserSight LSX excimer laser is safe, effective, and predictable and that with LASIK and PRK the results are stable when treating low to moderate myopia and astigmatism up to 4.0 D.     

Concurrent Accelerated Hyperfractionated Radiation Therapy and Carboplatin/etoposide in Patients With Malignant Glioma: Long-term break Results of A Phase II Study

Purpose: Feasibility, antitumor activity and toxicity of accelerated hyperfractionated radiation therapy (Acc Hfx RT) and concurrent carboplatin/etoposide (CBDCA/VP 16) chemotherapy were investigated in patients with malignant glioma. Material and methods: Seventy-nine patients with either glioblastoma multiforme (GBM) (n = 61) or anaplastic astrocytome (AA) (n = 18) entered into a phase II study on the use of Acc Hfx RT with 60Gy in 40 fractions in 20 treatment days over 4 weeks and concurrent CBDCA, 200mg/m², and VP 16, 200mg/m², both given once weekly during the RT course. Results: The median survival time for all 79 patients was 14 months (11 and 44 months for GBM and AA patients, respectively), while the 2- and 4-year survival was respectively 33% and 11% for all patients, 13% and 1.6% for GBM patients, and 100% and 44% for AA patients (p < 0.0001). The median time to progression for all patients was 12 months (9 and 40 months for GBM and AA, respectively), while the 2- and 4-year progression-free survival (PFS) was respectively 28% and 10% (all patients), 10% and 1.7% (GBM) and 89% and 39% (AA) (p < 0.0001). Multivariate analysis showed that age, performance status, and preoperative size of tumor influenced survival in GBM. Only 5 (6%) patients experienced grade 3 leukopenia and 6 (8%) patients experienced grade 3 thrombocytopenia. No late RT-induced toxicity was observed to date. Conclusions: Although Acc Hfx RT/CBDCA + VP 16 was feasible and little toxic, it failed to improve survival/progression-free survival over that obtained with other currently used regimens. These results do not justify the investigation of this regimen in a phase III trial.     

Lichen planus and other cutaneous manifestations in chronic hepatitis C: pre- and post-interferon-based treatment prevalence vary in a cohort of patients from low hepatitis C virus endemic area

Background Several controversies exist regarding the relationship between hepatitis C virus (HCV) infection and some cutaneous manifestations, lichen planus (LP) in particular. Objectives To determine the prevalence of LP and other cutaneous manifestations in a cohort of patients infected with HCV from low HCV endemic area of Slovenia, to correlate findings with chosen biological variables and to assess the role of interferon (IFN)‐based treatment of HCV infection in cutaneous manifestations. Methods A total of 171 consecutive HCV‐seropositive patients and 171 HCV‐seronegative age‐ and gender‐matched controls were studied prospectively. Prevalence of cutaneous manifestations, comparison between study patients and controls and correlation of skin findings with demographic, biochemical, virological and liver histologic findings as well as IFN‐based therapy were assessed. Results Overall presence of LP in HCV‐seropositives was 2.3%; although LP was not found in controls, the difference was not statistically significant (P = 0.123). Significantly higher than in controls was the prevalence of pruritus (31.0%, P < 0.001), dry skin (16.4%, P < 0.001) and hair loss (9.9%, P < 0.001). In IFN‐based treatment naïves, skin findings were more frequent compared with controls, but not significantly, with no correlation to chosen biological variables. Current IFN‐based treatment was significantly connected to pruritus (P < 0.001) and dry skin (P < 0.001). Compared with treatment naïves, in post‐treated patients pruritus (odds ratio, 19.13; 95% confidence interval, 6.85–53.42; P < 0.001), dry skin (odds ratio, 4.21; 95% confidence interval, 1.44–12.31; P < 0.001) and hair loss (P < 0.001) were significantly more common. Conclusions LP was not significantly related to HCV infection. Prevalence of pruritus, dry skin and hair loss was significantly higher in post‐compared with pre‐treated patients. The role of IFN in post‐treatment persistence of skin manifestations needs to be assessed.     

Lumbar zygapophysial (facet) joint radiofrequency denervation success as a function of pain relief during diagnostic medial branch blocks: a multicenter analysis.

BACKGROUND CONTEXT: The publication of several recent studies showing minimal benefit for radiofrequency (RF) lumbar zygapophysial (l-z) joint denervation have led many investigators to reevaluate selection criteria. One controversial explanation for these findings is that the most commonly used cutoff value for selecting patients for l-z (facet) joint RF denervation, greater than 50% pain relief after diagnostic blocks, is too low and hence responsible for the high failure rate. PURPOSE: To compare l-z joint RF denervation success rates between the conventional greater than or equal to 50% pain relief threshold and the more stringently proposed greater than or equal to 80% cutoff for diagnostic medial branch blocks (MBB). STUDY DESIGN/SETTING: Multicenter, retrospective clinical data analysis. PATIENT SAMPLE: Two hundred and sixty-two patients with chronic low back pain who underwent l-z RF denervation at three pain clinics. OUTCOME MEASURES: Outcome measures were greater than 50% pain relief based on visual analog scale or numerical pain rating score after RF denervation persisting at least 6 months postprocedure, and global perceived effect (GPE), which considered pain relief, satisfaction and functional improvement. METHODS: Data were garnered at three centers on 262 patients who underwent l-z RF denervation after obtaining greater than or equal to 50% pain relief after diagnostic MBB. Subjects were separated into those who received partial (greater than or equal to 50% but less than 80%) and near-complete (greater than or equal to 80%) pain relief from the MBB. Outcomes between groups were compared with multivariate analysis after controlling for 14 demographic and clinical variables. RESULTS: One hundred and forty-five patients obtained greater than or equal to 50% but less than 80% pain relief after diagnostic MBB, and 117 patients obtained greater than or equal to 80% relief. In the greater than or equal to 50% group, success rates were 52% and 67% based on pain relief and GPE, respectively. Among patients who experienced greater than 80% relief from diagnostic blocks, 56% obtained greater than or equal to 50% relief from RF denervation and 66% had a positive GPE. CONCLUSIONS: Using more stringent pain relief criteria when selecting patients for l-z joint RF denervation is unlikely to improve success rates, and may lead to misdiagnosis and withholding a potentially valuable treatment from good candidates.