The Role of Tibial Plateau Angle in Canine Cruciate Ligament Rupture-A Review of the Literature.

Cranial cruciate ligament disease is a common pathological condition in dogs that is often presented in daily clinical practice. Different risk factors for the development of this condition include breed, sex, age, bodyweight and neuter status, as well as different biological and biomechanical mechanisms. In the literature, special attention has been paid to the role of the tibial plateau angle in damage to the cranial cruciate ligament. Although the disease was first described at the beginning of last century, and since then different surgical methods have been developed to treat it, its aetiology remains unclear. In this review, contemporary literature data related to the role of tibial plateau angle in canine cranial cruciate ligament rupture are presented.

Survival of Women Previously Diagnosed of Melanoma with Subsequent Pregnancy: A Systematic Review and Meta-Analysis and a Single-Center Experience.

Melanoma incidence has increased over the last few decades. How the prognosis of a previously diagnosed melanoma may be affected by a woman's subsequent pregnancy has been debated in the literature since the 1950s, and the outcomes are essential to women who are melanoma survivors in their childbearing years. The main objective of this systematic review is to improve the understanding of whether the course of melanoma in a woman may be altered by a subsequent pregnancy and to help clinicians' diagnosis. Eligible studies for the systematic review were clinical trials, observational cohort studies and case-control studies that compared prognosis outcomes for non-pregnant patients with melanoma, or pregnant before melanoma diagnosis, versus pregnant patients after a diagnosis of melanoma. The search strategy yielded 1101 articles, of which 4 met the inclusion criteria for the systematic review. All the studies were retrospective non-randomised cohorts with patients with melanomas diagnosed before pregnancy. According to our findings, a subsequent pregnancy was not a significant influence on the outcome of a previous melanoma. However, given the small number of identified studies and the heterogeneous data included, it is recommended to approach these patients with caution, and counselling should be given by known prognostic factors. We also reviewed the medical records of 84 patients of childbearing age (35.8 ± 6.3 years, range 21-45 years) who were diagnosed with cutaneous invasive melanoma in our hospital between 2008 and 2018 (N = 724). Of these, 11 (13.1%) had a pregnancy after melanoma diagnosis (age at pregnancy: 35.6 ± 6.3 years). No statistical differences in outcome were detected.

Cross-cultural adaptation and validation of the Ukrainian version of the ABILHAND-Kids questionnaire.

PURPOSE: To develop and cross-culturally validate the Ukrainian version of the ABILHAND-Kids questionnaire by testing its psychometric properties in a sample of Ukrainian children with cerebral palsy. METHODS: The ABILHAND-Kids questionnaire was translated into Ukrainian, cross-culturally adapted, and administered to 113 parents of children with cerebral palsy. The psychometric properties of the Ukrainian version and its cross-cultural validation were investigated through the Rasch rating scale model. RESULTS: One major misfit has been found for the item "Rolling up a sleeve of a sweater" that further was removed. The item "Putting on a backpack/schoolbag" was split into gender-specific items, separately for girls and for boys, as it was systematically easier for Ukrainian girls. All remaining items contributed to the definition of a unidimensional measure of manual ability. The internal consistency reliability of the scale was high (R = 0.95). No significant floor (4%) and ceiling effects (5%) were observed. Three major differential item functioning items were found across Belgium and Ukraine, highlighting the need to use the Ukrainian calibration of ABILHAND-Kids in Ukraine. CONCLUSION: The Ukrainian ABILHAND-Kids questionnaire has good psychometric properties for assessing manual ability in Ukrainian children with cerebral palsy, holding potential to be implemented in clinical practice nationwide.Implications for rehabilitationCerebral palsy impairs manual ability leading to decreased quality of life and participation.Professionals need valid and reliable tools to detect small changes of manual ability during rehabilitation.Metric properties and availability of the Ukrainian version of the ABILHAND-Kids questionnaire make it a useful tool in the assessment of children with cerebral palsy.

Spatial Subchondral Bone Density Reflecting Joint Loading of the Talus in Different Canidae.

OBJECTIVE: Subchondral bone density distribution can be used to study joint biomechanics non-invasively. Differences in joint loading between related species can aid in the understanding of joint loading and the development of certain types of orthopaedic pathology. This study was conducted to evaluate density distribution in the subchondral bone of the talus of different Canidae species, as a parameter reflecting the long-term joint loading in the tarsocrural joint. MATERIALS AND METHODS: The tarsal joints of cadaveric dogs of different breeds were included, that is, German Shepherd (n = 5), Bouvier des Flandres (n = 3) and Labrador Retriever (n = 6).Additionally, golden jackals (n = 5) (Canis aureus) and wolves (n = 5) (Canis lupus) were included. Consecutive computed tomography slices were made and the subchondral bone density distribution was evaluated using computer tomographic osteoabsorptiometry. Different breeds and species were visually compared. RESULTS: Differences were found in the subchondral bone density distribution of the talus between breeds and between species (Canis familiaris, Canis lupus and Canis aureus). DISCUSSION AND CONCLUSION: Based on the density distribution, there are differences in loading conditions of the tarsocrural joint in different species of Canidae. The joint loading distribution is very similar between dogs of the same breed and within the same species. Although between-breed differences can be explained by conformational differences, the between-species differences remain subject to further research.

Xanthine Oxidase Activity in Type 2 Diabetes Mellitus Patients with and without Diabetic Peripheral Neuropathy.

This study investigated the relationship between serum xanthine oxidase (XOD) activity and the occurrence of diabetic peripheral neuropathy (DPN) in type 2 diabetes mellitus (T2DM) patients. Serum XOD activity, ischemia-modified albumin (IMA), uric acid (UA), albumin, glycated hemoglobin (HbA1c), advanced glycation end products (AGE), total free thiols, atherogenic index of plasma (AIP), and body mass index (BMI) were measured in 80 T2DM patients (29 with and 51 without DPN), and 30 nondiabetic control subjects. Duration of diabetes, hypertension, medication, and microalbuminuria was recorded. Serum XOD activities in controls, non-DPN, and DPN were 5.7 ± 2.4 U/L, 20.3 ± 8.6 U/L, and 27.5 ± 10.6 U/L (p < 0.01), respectively. XOD activity was directly correlated to IMA, UA, BMI, HbA1c, and AGE, while inversely correlated to serum total free thiols. A multivariable logistic regression model, which included duration of diabetes, hypertension, AIP, HbA1c, UA, and XOD activity, revealed HbA1c [OR = 1.03 (1.00-1.05); p = 0.034] and XOD activity [OR = 1.07 (1.00-1.14); p = 0.036] as independent predictors of DPN. Serum XOD activity was well correlated to several other risk factors. These results indicate the role of XOD in the development of DPN among T2DM patients.

Viscoelastic properties of uncured resin composites: Dynamic oscillatory shear test and fractional derivative model.

OBJECTIVE: In this study we analyze viscoelastic properties of three flowable (Wave, Wave MV, Wave HV) and one universal hybrid resin (Ice) composites, prior to setting. We developed a mathematical model containing fractional derivatives in order to describe their properties. METHODS: Isothermal experimental study was conducted on a rheometer with parallel plates. In dynamic oscillatory shear test, storage and loss modulus, as well as the complex viscosity where determined. We assumed four different fractional viscoelastic models, each belonging to one particular class, derivable from distributed-order fractional constitutive equation. The restrictions following from the Second law of thermodynamics are imposed on each model. The optimal parameters corresponding to each model are obtained by minimizing the error function that takes into account storage and loss modulus, thus obtaining the best fit to the experimental data. RESULTS: In the frequency range considered, we obtained that for Wave HV and Wave MV there exist a critical frequency for which loss and storage modulus curves intersect, defining a boundary between two different types of behavior: one in which storage modulus is larger than loss modulus and the other in which the situation is opposite. Loss and storage modulus curves for Ice and Wave do not show this type of behavior, having either elastic, or viscous effects dominating in entire frequency range considered. SIGNIFICANCE: The developed models may be used to predict behavior of four tested composites in different flow conditions (different deformation speed), thus helping to estimate optimal handling characteristics for specific clinical applications.

Interferon alpha for the adjuvant treatment of cutaneous melanoma.

BACKGROUND: Interferon alpha is the only agent approved for the postoperative adjuvant treatment of high-risk cutaneous melanoma. However, the survival advantage associated with this treatment is unclear, especially in terms of overall survival. Thus, adjuvant interferon is not universally considered a gold standard treatment by all oncologists. OBJECTIVES: To assess the disease-free survival and overall survival effects of interferon alpha as adjuvant treatment for people with high-risk cutaneous melanoma. SEARCH METHODS: We searched the following databases up to August 2012: the Cochrane Skin Group Specialised Register, CENTRAL in The Cochrane Library (2012, issue 8), MEDLINE (from 2005), EMBASE (from 2010), AMED (from 1985), and LILACS (from 1982). We also searched trials databases in 2011, and proceedings of the ASCO annual meeting from 2000 to 2011. We checked the reference lists of selected articles for further references to relevant trials. SELECTION CRITERIA: We included only randomised controlled trials (RCTs) comparing interferon alpha to observation (or any other treatment) for the postoperative (adjuvant) treatment of patients with high-risk skin melanoma, that is, people with regional lymph node metastasis (American Joint Committee on Cancer (AJCC) TNM (tumour, lymph node, metastasis) stage III) undergoing radical lymph node dissection, or people without nodal disease but with primary tumour thickness greater than 1 mm (AJCC TNM stage II). DATA COLLECTION AND ANALYSIS: Two authors extracted data, and a third author independently verified the extracted data. The main outcome measure was the hazard ratio (HR), which is the ratio of the risk of the event occurring in the treatment arm (adjuvant interferon) compared to the control arm (no adjuvant interferon). The survival data were either entered directly into Review Manager (RevMan) or extrapolated from Kaplan-Meier plots and then entered into RevMan. Based on the presence of between-study heterogeneity, we applied a fixed-effect or random-effects model for calculating the pooled estimates of treatment efficacy. MAIN RESULTS: Eighteen RCTs enrolling a total of 10,499 participants were eligible for the review. The results from 17 of 18 of these RCTs, published between 1995 and 2011, were suitable for meta-analysis and allowed us to quantify the therapeutic efficacy of interferon in terms of disease-free survival (17 trials) and overall survival (15 trials). Adjuvant interferon was associated with significantly improved disease-free survival (HR (hazard ratio) = 0.83; 95% CI (confidence interval) 0.78 to 0.87, P value < 0.00001) and overall survival (HR = 0.91; 95% CI 0.85 to 0.97; P value = 0.003). We detected no significant between-study heterogeneity (disease-free survival: I² statistic = 16%, Q-test P value = 0.27; overall survival: I² statistic = 6%; Q-test P value = 0.38).Considering that the 5-year overall survival rate for TNM stage II-III cutaneous melanoma is 60%, the number needed to treat (NNT) is 35 participants (95% CI = 21 to 108 participants) in order to prevent 1 death. The results of subgroup analysis failed to answer the question of whether some treatment features (i.e. dosage, duration) might have an impact on interferon efficacy or whether some participant subgroups (i.e. with or without lymph node positivity) might benefit differently from interferon adjuvant treatment.Grade 3 and 4 toxicity was observed in a minority of participants: In some trials, no-one had fever or fatigue of Grade 3 severity, but in other trials, up to 8% had fever and up to 23% had fatigue of Grade 3 severity. Less than 1% of participants had fever and fatigue of Grade 4 severity. Although it impaired quality of life, toxicity disappeared after treatment discontinuation. AUTHORS' CONCLUSIONS: The results of this meta-analysis support the therapeutic efficacy of adjuvant interferon alpha for the treatment of people with high-risk (AJCC TNM stage II-III) cutaneous melanoma in terms of both disease-free survival and, though to a lower extent, overall survival. Interferon is also valid as a reference treatment in RCTs investigating new therapeutic agents for the adjuvant treatment of this participant population. Further investigation is required to select people who are most likely to benefit from this treatment.

Interactions between glycine transporter type 1 (GlyT-1) and some inhibitor molecules - glycine transporter type 1 and its inhibitors (review).

Glycine is a mandatory positive allosteric modulator of N-methyl-D-aspartate (NMDA)-type ionotropic glutamate receptors in the central nervous system. Elevation of glycine concentrations by inhibition of its reuptake in the vicinity of NMDA receptors may positively influence receptor functions as glycine B binding site on NR1 receptor subunit is not saturated in physiological conditions. Synaptic and extrasynaptic concentrations of glycine are regulated by its type-1 glycine transporter, which is primarily expressed in astroglial and glutamatergic cell membranes. Alteration of synaptic glycine levels may have importance in the treatment of various forms of endogenous psychosis characterized by hypofunctional NMDA receptors. Several lines of evidence indicate that impaired NMDA receptor-mediated glutamatergic neurotransmission is involved in development of the negative (and partly the positive) symptoms and the cognitive deficit in schizophrenia. Inhibitors of glycine transporter type-1 may represent a newly developed therapeutic intervention in treatment of this mental illness. We have synthesized a novel series of N-substituted sarcosines, analogues of the glycine transporter-1 inhibitor NFPS (N-[3-(4'-fluorophenyl)-3-(4'-phenylphenoxy)-propyl]sarcosine). Of the pyridazinone-containing compounds, SzV-1997 was found to be a potent glycine transporter-1 inhibitor in rat brain synaptosomes and it markedly increased extracellular glycine concentrations in conscious rat striatum. SzV-1997 did not exhibit toxic symptoms such as hyperlocomotion, restless movements, respiratory depression, and lethality, characteristic for NFPS. Besides pyridazinone-based, sarcosine-containing glycine transporter-1 inhibitors, a series of substrate-type amino acid inhibitors was investigated in order to obtain better insight into the ligand-binding characteristics of the substrate binding cavity of the transporter.

Surgical excision margins for primary cutaneous melanoma.

BACKGROUND: Cutaneous melanoma accounts for 75% of skin cancer deaths. Standard treatment is surgical excision with a safety margin some distance from the borders of the primary tumour. The purpose of the safety margin is to remove both the complete primary tumour and any melanoma cells that might have spread into the surrounding skin.Excision margins are important because there could be trade-off between a better cosmetic result but poorer long-term survival if margins become too narrow. The optimal width of excision margins remains unclear. This uncertainty warrants systematic review. OBJECTIVES: To assess the effects of different excision margins for primary cutaneous melanoma. SEARCH STRATEGY: In August 2009 we searched for relevant randomised trials in the Cochrane Skin Group Specialised Register; the Cochrane Central Register of Controlled Trials (CENTRAL) in The Cochrane Library (Issue 3, 2009), MEDLINE, EMBASE, LILACS, and other databases including Ongoing Trials Registers. SELECTION CRITERIA: We considered all randomised controlled trials (RCTs) of surgical excision of melanoma comparing different width excision margins. DATA COLLECTION AND ANALYSIS: We assessed trial quality, and extracted and analysed data on survival and recurrence. We collected adverse effects information from included trials. MAIN RESULTS: We identified five trials. There were 1633 participants in the narrow excision margin group and 1664 in the wide excision margin group. Narrow margin definition ranged from 1 to 2 cm; wide margins ranged from 3 to 5 cm. Median follow-up ranged from 5 to 16 years. AUTHORS' CONCLUSIONS: This systematic review summarises the evidence regarding width of excision margins for primary cutaneous melanoma. None of the five published trials, nor our meta-analysis, showed a statistically significant difference in overall survival between narrow or wide excision.The summary estimate for overall survival favoured wide excision by a small degree [Hazard Ratio 1.04; 95% confidence interval 0.95 to 1.15; P = 0.40], but the result was not significantly different. This result is compatible with both a 5% relative reduction in overall mortality favouring narrower excision and a 15% relative reduction in overall mortality favouring wider excision. Therefore, a small (but potentially important) difference in overall survival between wide and narrow excision margins cannot be confidently ruled out.The summary estimate for recurrence free survival favoured wide excision [Hazard Ratio 1.13; P = 0.06; 95% confidence interval 0.99 to 1.28] but again the result did not reach statistical significance (P < 0.05 level).Current randomised trial evidence is insufficient to address optimal excision margins for primary cutaneous melanoma.

Anterior tab flap versus standard underlay myringoplasty in children.

OBJECTIVES: Tympanic membrane (TM) perforation closure can present a problem in children, especially in anterior and total perforations, because of the anterior's lack of support for the graft. It was suggested that the anterior tab flap (ATF) myringoplasty, an underlay graft with an anterior tab under the TM annulus, could provide better stability of the graft. We undertook a prospective, randomized, controlled study to compare the ATF myringoplasty with the standard underlay (SU) myringoplasty in children. METHODS: We randomly assigned 59 children to undergo ATF myringoplasty and 52 to undergo SU myringoplasty at a tertiary care pediatric institution. Surgery was performed under general anesthesia in all patients. The primary outcome was the healing of the TM; the secondary outcomes were anterior blunting of the graft and presence of retraction of the TM. Two years of follow-up were obtained in all enrolled children. RESULTS: At 2 years of follow-up, there were 55 stable TM closures in the ATF arm and 44 in the SU arm. Although the TM closure was higher in the ATF arm than in the SU arm (93.2 and 84.6%, respectively), the results were not statistically significant (odds ratio = 0.4, 95% confidence interval = 0.12-1.41). Anterior blunting and TM retraction were not encountered. CONCLUSION: The ATF myringoplasty is a safe and effective method for TM closure in children. However, compared with the SU myringoplasty, the ATF myringoplasty is not associated with an overall decrease in the incidence of the residual perforations. Further assessment in a larger study is proposed.

Contact-diode laser repair of bony choanal atresia: a preliminary report.

OBJECTIVES: To demonstrate the use of the contact-diode laser (CDL) at 810 nm wavelength for the transnasal endoscopic repair of bilateral bony choanal (BBCA) in low-weight newborns. METHODS: Prospective study at a tertiary-care pediatric institution of four neonates with BBCA aged 3-5 days, weighing on average 2.34 kg. BBCA was opened by transnasal delivery of CDL through a 600 microm diameter glass fiber. Children were stented post-operatively, and revision surgery performed when needed. RESULTS: All children were successfully treated for BBCA with CDL. Two children needed only one surgery, one child needed two surgeries, and one patient required three procedures, in order to establish patient choanae at last follow-up ranging from 16 to 30 months. CONCLUSION: We found the fiber-delivered contact-diode laser to permit correction of BBCA in four low-birth weight neonates. To the best of our knowledge, this report is the first to demonstrate the successful use of CDL for the management of BBCA.

Excision margins for primary cutaneous melanoma: updated pooled analysis of randomized controlled trials.

OBJECTIVE: To determine the effectiveness of wide vs narrow excision margins in the treatment of primary cutaneous melanoma. DATA SOURCES: We conducted a search of MEDLINE and the Cochrane Controlled Trials Register as well as a manual search of the reference lists of all relevant papers. No language or date restrictions were applied. STUDY SELECTION: Only prospective randomized trials were included. DATA EXTRACTION: Two reviewers independently extracted the data from each study. Outcomes evaluated were local and locoregional recurrences and overall mortality. Data were analyzed using Cochrane Collaboration Review Manager software. DATA SYNTHESIS: Five randomized trials comprising 3313 participants were retrieved and analyzed. Pooled data showed no statistically significant difference in overall mortality when comparing wide vs narrow excision margins (odds ratio, 0.98; 95% confidence interval, 0.72-1.22; and test for overall effect of P = .88). There was no statistically significant difference in the occurrence of locoregional recurrence between 2 groups of patients (odds ratio, 1.18; 95% confidence interval, 0.98-1.41; and test for overall effect not significant at P = .08). Although statistically significant heterogeneity was not detected among included trials, there was considerable clinical heterogeneity. CONCLUSIONS: Although this meta-analysis did not show any statistically significant difference between patients treated with wide or narrow excision margins insofar as overall mortality and locoregional and local recurrences, current evidence is insufficient to address the optimal excision margins for all types of melanomas. Further research is required to establish the appropriate local treatment for different types of primary melanoma and subgroups of patients.

Neuroprotective and anticonvulsant effects of EGIS-8332, a non-competitive AMPA receptor antagonist, in a range of animal models.

BACKGROUND AND PURPOSE: Blockade of AMPA (alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid) receptors is a good treatment option for a variety of central nervous system disorders. The present study evaluated the neuroprotective and anticonvulsant effects of EGIS-8332, a non-competitive AMPA receptor antagonist, as a potential drug candidate. EXPERIMENTAL APPROACH: AMPA antagonist effects of EGIS-8332 were measured using patch-clamp techniques. Neuroprotective and anticonvulsant effects of EGIS-8332 were evaluated in various experimental models, relative to those of GYKI 53405. KEY RESULTS: EGIS-8332 inhibited AMPA currents in rat cerebellar Purkinje cells and inhibited the AMPA- and quisqualate-induced excitotoxicity in primary cultures of telencephalon neurons (IC(50)=5.1-9.0 microM), in vitro. Good anticonvulsant actions were obtained in maximal electroshock-, sound- and chemically-induced seizures (range of ED(50)=1.4-14.0 mg kg(-1) i.p.) in mice. Four days after transient global cerebral ischaemia, EGIS-8332 decreased neuronal loss in the hippocampal CA1 area in gerbils and rats. EGIS-8332 dose-dependently reduced cerebral infarct size after permanent middle cerebral artery occlusion in mice and rats (minimum effective dose=3 mg kg(-1) i.p.). Side effects of EGIS-8332 emerged much above its pharmacologically active doses. A tendency for better efficacy of GYKI 53405 than that of EGIS-8332 was observed in anticonvulsant tests that reached statistical significance in few cases, while the contrary was perceived in cerebral ischaemia tests. CONCLUSIONS AND IMPLICATIONS: EGIS-8332 seems suitable for further development for the treatment of epilepsy, ischaemia and stroke based on its efficacy in a variety of experimental disease models, and on its low side effect potential.

Mechanisms underlying the long-term behavioral effects of traumatic experience in rats: the role of serotonin/noradrenaline balance and NMDA receptors.

Traumatic stressors induce long-lasting changes in behavior. It is believed that all three glutamatergic, serotonergic and noradrenergic neurotransmission play a role in the development of such behavioral changes, but their relative importance and relationship is poorly understood. We have shown previously that a single exposure of rats to electric shocks induces social avoidance for about 10 days. Here we assessed social avoidance 24 h after shock exposure in rats with chemically lesioned serotonergic and noradrenergic neurons. The effects of the NMDA receptor blocker MK-801 were also studied. When the serotonin/noradrenaline balance was shifted towards serotonergic dominance via chemical lesions, the behavioral dysfunction was markedly attenuated. The disruption of serotonergic neurotransmission (that lead to noradrenergic dominance) significantly increased the behavioral deficit. Shock responding was not secondary to lesion-induced differences in social behavior. Noteworthy, the brain noradrenaline/serotonin ratio correlated negatively with shock-induced social avoidance, suggesting that the ratio rather than absolute levels are important in this respect. In line with this assumption, double lesions had minor effects on social avoidance, suggesting that these monoaminergic systems modulate, but do not mediate the behavioral deficit. The blockade of NMDA receptors abolished the development of stress-induced social avoidance both when applied before shocks and when applied before behavioral testing. We confirmed that the long-term behavioral effects of traumatic experience result from glutamatergic activation, the effects of which are mediated by NMDA receptors. The development of the behavioral deficit is modulated by the balance between serotonergic and noradrenergic neurotransmission, possibly via effects on shock-induced glutamatergic activation.

Effect of pregnancy on survival in women with cutaneous malignant melanoma.

PURPOSE: An adverse influence of pregnancy on the risk of death in women with cutaneous melanoma was suggested historically by anecdotal reports. Previous studies included small numbers of women observed for short periods. METHODS: Using data from the Swedish National and Regional Registries, we performed a retrospective cohort study of all Swedish women who were diagnosed with cutaneous melanoma during their reproductive period, from January 1, 1958, to December 31, 1999. The relationship between pregnancy status at the diagnosis of melanoma and overall survival was examined in multivariable proportional-hazards models. RESULTS: The cohort comprised 185 women (3.3%) diagnosed with melanoma during pregnancy and 5,348 (96.7%) women of the same childbearing age diagnosed with melanoma while not pregnant. There was no statistically significant difference in overall survival between pregnant and nonpregnant groups (log-rank chi(2)1[r] = 0.84, P = .361). Pregnancy status at the time of diagnosis of melanoma was not related to survival in a multivariable Cox model in the 2,101 women (hazard ratio for death in the pregnant group was 1.08; 95% CI, 0.60 to 1.93). In the multivariable analysis, pregnancy status after diagnosis of melanoma was not a significant predictor of survival (hazard ratio for death in women who had pregnancy subsequent to the diagnosis of melanoma was 0.58; 95% CI, 0.32 to 1.05). CONCLUSION: The survival of pregnant women with melanoma is not worse than the survival of nonpregnant women with melanoma. Pregnancy subsequent to the diagnosis of primary melanoma was not associated with an increased risk of death.

Systemic chemotherapy in the treatment of malignant melanoma.

Different postsurgical therapies are used for the treatment of metastatic melanoma. This article reviews the use of chemotherapeutic agents in the treatment of patients with metastatic malignant melanoma. A variety of single chemotherapy agents have been evaluated, although the most widely used chemotherapeutic in the treatment of metastatic melanoma is dacarbazine. In order to improve the rate and duration of responses, combination chemotherapy was developed. The most common combined chemotherapy regimens used as standard for the treatment of metastatic melanoma are Dartmouth regimen, CVD (cisplatin + vinblastine + dacarbazine) and BOLD (bleomycin + vincristine + lomustine + dacarbazine). However, Phase III trials have failed to demonstrate a significant benefit in survival in patients treated with polychemotherapy compared to those treated with dacarbazine alone. The use of classical systemic chemotherapy still has a role in the treatment of patients with metastatic melanoma. Immunotherapy and biochemotherapy have no additional advantage over chemotherapy.

The role of biological response modifiers in malignant melanoma.

This article reviews the existing data in an attempt to address the role of biological response modifiers (IFN-alpha and IL-2) in the management of melanoma. Eight prospective controlled Phase III trials evaluating IFN-alpha therapy are discussed. As the results from these trials have been heterogeneous and inconsistent, the role of IFN-alpha in the adjuvant treatment of stage II and III melanoma patients remains to be defined. IL-2 possesses modest antitumour activity in melanoma yielding objective response in approximately 15% of patients. Many toxic effects are induced by high-dose IL-2 therapy. Combinations of chemotherapy and biological response modifiers and their impact on tumour response and survival are discussed.

Use of tamoxifen in the treatment of malignant melanoma.

BACKGROUND: Tamoxifen has been used in the treatment of patients with metastatic malignant melanoma either as a single agent or, more commonly, in combination with other chemotherapeutic agents. The aim of the current study was to summarize the available clinical evidence on the role of the tamoxifen in different combination chemotherapy regimens because clinical studies including tamoxifen have produced inconclusive results. METHODS: The authors designed a systematic review and metaanalysis of published randomized controlled trials to assess the benefit of tamoxifen added to various single-agent or multiagent chemotherapy or biochemotherapy regimens. RESULTS: Six randomized trials met the inclusion criteria and were analyzed. These 6 trials involved a combined total of 912 patients. Of this number, 455 patients were randomized to receive tamoxifen added to chemotherapy or biochemotherapy regimens and 457 were randomized to receive chemotherapy or biochemotherapy without tamoxifen. The overall response rate was not improved significantly by the addition of tamoxifen to the chemotherapy regimen (odds ratio [OR], 1.16; 95% confidence interval [CI], 0.75-1.82; test for overall effect: P = 0.14). The results were not statistically significant for complete response (OR, 0.64; 95% CI, 0.33-1.25; test for overall effect: P = 0.19). CONCLUSIONS: The current metaanalysis demonstrated that tamoxifen does not improve the overall response rate, complete response rate, or survival rate when administered along with combined chemotherapy regimens. Currently, the strength of evidence does not support the use of tamoxifen in combination with other systemic chemotherapy for the treatment of metastatic melanoma.