Multibipolar Radiofrequency Ablation for the Treatment of Mass-Forming and Infiltrative Hepatocellular Carcinomas > 5 cm: Long-Term Results.

AIMS AND BACKGROUND: Only few patients with cirrhosis and hepatocellular carcinoma (HCC) larger than 5 cm are amenable to resection or straight liver transplantation, and in such circumstances, multibipolar radiofrequency ablation (mbp-RFA) could be a reliable alternative. This study was aimed to assess the long-term outcome in patients treated with mbp-RFA for unresectable HCC > 5 cm. METHODS: Eighty-three consecutive patients with cirrhosis (median age 70 years [37-93 years], 67 males, BCLC A/B/C: 54/21/8, 74 naive) with up to three HCCs, the largest > 5 cm in diameter (median: 6.2 cm, 5.1-9 cm, 22 infiltrative forms, 12 with segmental portal invasion of which 10 were infiltrative forms) were treated with mbp-RFA. Overall (OS) and recurrence-free (RFS) survival and their associated predictive factors were assessed. RESULTS: Complete ablation was observed in 78/83 (94%) patients. Thirty-one side effects occurred, including 6 (7%) severe complications. After a median follow-up of 26.1 months (1-112 months), in naive patients the 3- and 5-year OS was 51% (38-62) and 24% (13-36), 63 and 30% for mass-forming and 25 and 6% for infiltrative form, respectively. Infiltrative form (HR: 2.5 [1.33-4.69], p = 0.004) was the only independent OS predictor. In naive patients with mass-forming and infiltrative form, the 3- and 5-year RFS were 47 and 17 and 18 and 18%, respectively. Alpha-fetoprotein (HR: 2.86 [1.32-6.21], p = 0.008), multinodular form (HR: 2.74 [1.4-5.38], p = 0.003) and infiltrative form (HR: 3.43 [1.67-7.01], p = 0.0007) were independent RFS predictors. CONCLUSIONS: mbp-RFA offers good OS in inoperable patients with cirrhosis and large HCC, with acceptable safety profile. For infiltrative forms, although mbp-RFA leads to complete responses in more than 80% cases, few only remain tumor progression-free in long-term.

Real-Time 3D Virtual Target Fluoroscopic Display for Challenging Hepatocellular Carcinoma Ablations Using Cone Beam CT.

Three-dimensional virtual target fluoroscopic display is a new guidance tool that can facilitate challenging percutaneous ablation. The purpose of this study was to assess the feasibility, local efficacy, and safety of liver ablation assisted by three-dimensional virtual target fluoroscopic display. Sixty-seven hepatocellular carcinomas (mean diameter: 31 mm, range: 9-90 mm, 24 ≥ 30 mm, 16 of an infiltrative form) in 53 consecutive patients were ablated using irreversible electroporation (n = 39), multibipolar radiofrequency (n = 25), or microwave (n = 3) under a combination of ultrasound and three-dimensional virtual target fluoroscopic display guidance because the procedures were considered to be unfeasible under ultrasound alone. This guidance technology consisted of real-time fluoroscopic three-dimensional visualization of the tumor previously segmented from cone beam computed tomography images acquired at the start of the procedure. The results were assessed by cross-sectional imaging performed at 1 month and then every 3 months in the event of complete ablation. Factors associated with overall local tumor progression (initial treatment failure and subsequent local tumor progression) were assessed using a logistic regression model. Sixty-one (91%) tumors were completely ablated after 1 (n = 53) or 2 (n = 8) procedures. After a median follow-up of 12.75 months (1-23.2) of the 61 tumors displaying imaging characteristics consistent with complete ablation at 1 month, local tumor progression was observed in 9, so the overall local tumor progression rate was 22.3% (15 of 67). Under multivariate analysis, dome locations and infiltrative forms were associated with local tumor progression. No major complications occurred. Three-dimensional virtual target fluoroscopic display is a feasible and efficient image guidance tool to facilitate challenging ablations that are generally considered as infeasible using ultrasound alone.

Association between a pro plant-based dietary score and cancer risk in the prospective NutriNet-santé cohort.

Diverse plant products (e.g. fruits, vegetables, legumes) are associated with decreased cancer risk at several locations while red and processed meat were found to increase cancer risk. A pro plant-based dietary score reflecting the relative contribution of consumed plant vs animal products was developed, and was associated with lower overall mortality, type 2 diabetes and cardiovascular disease risk, among omnivorous adults. For the first time, we investigated the prospective associations between this pro plant-based dietary score and cancer risk. This study included 42,544 men and women of the French NutriNet-Santé prospective cohort (2009-2016) aged ≥45 years who completed at least three 24-hr-dietary records during the first year of follow-up. The risk of developing cancer was compared across sex-specific tertiles of pro plant-based dietary score by multivariable Cox models. In total, 1,591 first primary incident cancer cases were diagnosed during follow-up, among which 487 breast, 243 prostate, 198 digestive and 68 lung cancers. A higher pro plant-based dietary score was associated with decreased risks of overall (HRt3vs.t1 =0.85; 95% CI 0.76, 0.97; Ptrend =0.02), digestive (HRt3vs.t1 =0.68; 95% CI 0.47; 0.99; Ptrend = 0.04) and lung (HRt3vs.t1 =0.47; 95% CI 0.25, 0.90; Ptrend =0.02) cancer, though no substantial associations were found for breast or prostate cancers. This large cohort study supports a beneficial role of higher intakes of plant-based products along with lower intakes of animal products, within a balanced omnivorous diet, regarding primary cancer prevention. These results are consistent with mechanistic evidence from experimental studies.

Red and processed meat intake and cancer risk: Results from the prospective NutriNet-Santé cohort study.

The International Agency for Research on Cancer (WHO-IARC) classified red meat and processed meat as probably carcinogenic and carcinogenic for humans, respectively. These conclusions were mainly based on studies concerning colorectal cancer, but scientific evidence is still limited for other cancer locations. In this study, we investigated the prospective associations between red and processed meat intakes and overall, breast, and prostate cancer risk. This prospective study included 61,476 men and women of the French NutriNet-Santé cohort (2009-2015) aged ≥35 y and who completed at least three 24 hrs dietary records during the first year of follow-up. The risk of developing cancer was compared across sex-specific quintiles of red and processed meat intakes by multivariable Cox models. 1,609 first primary incident cancer cases were diagnosed during follow-up, among which 544 breast cancers and 222 prostate cancers. Red meat intake was associated with increased risk of overall cancers [HRQ5vs.Q1 =1.31 (1.10-1.55), ptrend = 0.01) and breast cancer (HRQ5vs.Q1 = 1.83 (1.33-2.51), ptrend = 0.002]. The latter association was observed in both premenopausal [HRQ5vs.Q1 =2.04 (1.03-4.06)] and postmenopausal women [HRQ5vs.Q1 =1.79 (1.26-2.55)]. No association was observed between red meat intake and prostate cancer risk. Processed meat intake was relatively low in this study (cut-offs for the 5th quintile = 46 g/d in men and 29 g/d in women) and was not associated with overall, breast or prostate cancer risk. This large cohort study suggested that red meat may be involved carcinogenesis at several cancer locations (other than colon-rectum), in particular breast cancer. These results are consistent with mechanistic evidence from experimental studies.

Safety and Efficacy of Irreversible Electroporation for the Treatment of Hepatocellular Carcinoma Not Amenable to Thermal Ablation Techniques: A Retrospective Single-Center Case Series.

Purpose To assess the safety and efficacy of irreversible electroporation (IRE) in the treatment of patients with inoperable hepatocellular carcinoma (HCC) who are ineligible for thermal ablative techniques. Materials and Methods This retrospective study was approved by an ethics review board, and the requirement to obtain informed written consent was waived. From March 2012 to June 2015, 58 patients (median age, 65.4 years; range 41.6-90 years) with cirrhosis received IRE for the treatment of 75 HCC tumors. The median tumor diameter was 24 mm (range, 6-90 mm). IRE was selected because of tumor location (48 patients) or the patient's poor general condition (10 patients). Treatment response was assessed with magnetic resonance (MR) imaging 1 month after treatment and every 3 months thereafter. Overall local tumor progression-free survival (PFS) per nodule (including initial treatment failures) was assessed by using the Kaplan-Meier method. The marginal Cox proportional hazards model was used to assess the factors associated with overall local tumor PFS. Complications were recorded and graded according to the Clavien-Dindo classification. Results Of 75 tumors, 58 (77.3%), 67 (89.3%), and 69 (92%) were completely ablated after one, two, and three IRE procedures, respectively. After a median follow-up of 9 months (range, 3 days to 31 months), the 6- and 12-month overall local tumor PFS rates for the 75 treated nodules were 87% (95% confidence interval [CI]: 77%, 93%) and 70% (95% CI: 56%, 81%), respectively. A preablative serum α-fetoprotein level higher than 200 ng/mL (hazard ratio: 9.94 [95% CI: 2.82, 35.06], P = .0004) was the only factor linked with overall local tumor PFS. Complications occurred in 11 of the 58 patients (19%) and were classified as grade I in three patients, grade II in five patients, grade IV in two patients, and grade V in one patient. The three (5.2%) complications classified as grade III or higher were liver failures occurring in patients with Child-Pugh class B disease; one led to death. Conclusion IRE offers safe, complete ablation of HCC tumors in patients with contraindications to other commonly used ablative techniques. © RSNA, 2017 Online supplemental material is available for this article.

Dietary iron intake and breast cancer risk: modulation by an antioxidant supplementation.

Experimental results suggested that iron-induced lipid peroxidation may explain the direct associations observed between red/processed meat intakes and colorectal and breast cancer risk. However, epidemiological evidence is lacking. Thus, we investigated the association between dietary iron intake and breast cancer risk, and its potential modulation by an antioxidant supplementation and lipid intake. This prospective study included 4646 women from the SU.VI.MAX trial (daily low-dose antioxidants vs. placebo). 188 incident breast cancers were diagnosed (median follow-up=12.6y). Dietary iron intake was assessed using repeated 24h dietary records. Multivariable Cox proportional hazards models were computed. Dietary iron intake was associated with an increased breast cancer risk (HRT3vs.T1=1.67 (1.02-2.71), P-trend=0.04). This association was observed in the placebo group (HRT3vs.T1=2.80 (1.42-5.54), P-trend=0.003), but not in the antioxidant-supplemented group (P-trend=0.7, P-interaction=0.1). Besides, in the placebo group, the increased breast cancer risk associated with dietary iron intake was more specifically observed in women with higher lipid intake (P-trend=0.046). These findings suggest that dietary iron intake may be associated with an increased breast cancer risk, especially in women who did not received antioxidants during the trial and who consumed more lipids. This supports the experimental results suggesting that breast cancer risk may be increased by iron-induced lipid peroxidation.

Hepatocellular Carcinoma within Milan Criteria: No-Touch Multibipolar Radiofrequency Ablation for Treatment-Long-term Results.

Purpose To assess the long-term outcome in 108 consecutive patients treated with no-touch multibipolar radiofrequency ablation (RFA) for hepatocellular carcinoma (HCC) that met the Milan criteria. Materials and Methods This retrospective study was approved by the ethical review board, and the need to obtain informed consent was waived. Between November 1, 2006, and December 31, 2011, 132 HCC tumors (diameter, 10-45 mm; 39 tumors ≥ 30 mm) in 108 consecutive patients (106 with cirrhosis) that met Milan criteria were treated with no-touch multibipolar RFA, which consisted of activating, in bipolar mode, three or four electrodes inserted just beyond the tumor margins. Follow-up was performed every 3 months for 2 years and every 6 months thereafter with computed tomographic or magnetic resonance imaging. Survival probabilities were computed by using the Kaplan-Meier method. Predictive factors of tumor progression and overall survival were assessed by using the Cox proportional hazard model. Results No technical failure occurred, and complete ablation was achieved for all the nodules. After a median of 40.5 months (range, 2-84 months) of follow-up, 3- and 5-year local and overall tumor progression-free survival were 96%, 94%, 52%, and 32%, respectively. Neither tumor diameter greater than 30 mm nor location abutting a large vessel were associated with local tumor progression. Tumor diameter greater than 30 mm was the only parameter predictive of overall tumor progression (P = .0036). Independent factors associated with shorter overall survival were Child-Pugh class B disease, age greater than 65 years, and platelet count of less than 150 g/L (P < .003). Three major complications occurred (2.7%): hemothorax in one patient and liver failure in two, with major portal-systemic shunts. One patient (0.9%) died, and one underwent transplantation. Conclusion No-touch multibipolar RFA for HCC tumors that meet Milan criteria provides a high local tumor progression-free survival rate. An ongoing randomized trial might help to clarify the role of this new approach for the treatment of early HCC. (©) RSNA, 2016 Online supplemental material is available for this article. An earlier incorrect version of this article appeared online. This article was corrected on March 30, 2016.

Associations between fruit, vegetable and legume intakes and prostate cancer risk: results from the prospective Supplémentation en Vitamines et Minéraux Antioxydants (SU.VI.MAX) cohort.

Although experimental studies suggest that fruits, vegetables and legumes may exert protective effects against prostate carcinogenesis through various bioactive compounds such as dietary fibre and antioxidants, epidemiological evidence is lacking. Notably, very few prospective studies have investigated the relationship between legume intake and prostate cancer risk. Our objective was to prospectively investigate the association between fruit, vegetable, tomato products, potatoes and legume intakes and prostate cancer risk. This study included 3313 male participants to the SUpplémentation en VItamines et Minéraux AntioXydants cohort (follow-up: 1994-2007) who completed at least three 24-h dietary records during the first 2 years of follow-up. Associations between tertiles of intake and prostate cancer risk were assessed by multivariate Cox proportional hazards models. After a median follow-up of 12·6 years, 139 incident prostate cancers were diagnosed. An inverse association was observed between prostate cancer risk and tertiles of legume intake (hazard ratio (HR)T3v.T1=0·53; 95 % CI 0·34, 0·85; P trend=0·009). This association was maintained after excluding soya and soya products from the legume group (HRT3 v.T1=0·56; 95 % CI 0·35, 0·89; P trend=0·02). No association was observed between prostate cancer risk and tertiles of intakes of fruits (P trend=0·25), vegetables (P trend=0·91), potatoes (P trend=0·77) and tomato products (P trend=0·09). This prospective study confirms the null association between fruit and non-starchy vegetable intakes and prostate cancer risk observed in most previous cohorts. In contrast, although very few prospective studies have been published on the topic, our results suggest an inverse association between legume intake and prostate cancer risk, supported by mechanistic plausibility. These results should be confirmed by large-scale observational and intervention studies.

Sequential Serum Metabolomic Profiling after Radiofrequency Ablation of Hepatocellular Carcinoma Reveals Different Response Patterns According to Etiology.

Radiofrequency ablation (RFA) is commonly performed as a curative approach in patients with hepatocellular carcinoma (HCC); however, the risk of tumor recurrence is difficult to predict due to a lack of reliable clinical and biological markers, and identification of new biomarkers poses a major challenge for improving prognoses. Metabolomics is a promising technique that may lead to the identification and characterization of new disease fingerprints. The objective of the present study was to explore, preoperatively and at various time points post-RFA, the metabolic profile of serum samples from HCC patients to identify factors associated with treatment response and recurrence. Sequential sera obtained before and after RFA procedures for 120 patients with HCC due to cirrhosis were investigated using nuclear magnetic resonance metabolomics. A multilevel orthogonal projection to latent structure analysis was used to discriminate intraindividual metabolic changes in response to RFA treatment. Recurrence-free survival differed depending on the underlying cause of cirrhosis. The statistical model showed significant differences depending on whether the liver disease had a viral or nonviral etiology before RFA intervention (explained variance of R(2)Y = 0.89 and predictability of Q(2)Y = 0.34). These profiles were also associated with specific and distinct metabolic responses after RFA.

One-Year Mortality in Older Patients with Cancer: Development and External Validation of an MNA-Based Prognostic Score.

PURPOSE: The MNA (Mini Nutritional Assessment) is known as a prognosis factor in older population. We analyzed the prognostic value for one-year mortality of MNA items in older patients with cancer treated with chemotherapy as the basis of a simplified prognostic score. METHODS: The prospective derivation cohort included 606 patients older than 70 years with an indication of chemotherapy for cancers. The endpoint to predict was one-year mortality. The 18 items of the Full MNA, age, gender, weight loss, cancer origin, TNM, performance status and lymphocyte count were considered to construct the prognostic model. MNA items were analyzed with a backward step-by-step multivariate logistic regression and other items were added in a forward step-by-step regression. External validation was performed on an independent cohort of 229 patients. RESULTS: At one year 266 deaths had occurred. Decreased dietary intake (p = 0.0002), decreased protein-rich food intake (p = 0.025), 3 or more prescribed drugs (p = 0.023), calf circumference <31 cm (p = 0.0002), tumor origin (p<0.0001), metastatic status (p = 0.0007) and lymphocyte count <1500/mm3 (0.029) were found to be associated with 1-year mortality in the final model and were used to construct a prognostic score. The area under curve (AUC) of the score was 0.793, which was higher than the Full MNA AUC (0.706). The AUC of the score in validation cohort (229 subjects, 137 deaths) was 0.698. CONCLUSION: Key predictors of one-year mortality included cancer cachexia clinical features, comorbidities, the origin and the advanced status of the tumor. The prognostic value of this model combining a subset of MNA items and cancer related items was better than the full MNA, thus providing a simple score to predict 1-year mortality in older patients with an indication of chemotherapy.

Prospective association between dietary folate intake and skin cancer risk: results from the Supplémentation en Vitamines et Minéraux Antioxydants cohort.

BACKGROUND: The role of folate in skin carcinogenesis is unclear, with experimental data suggesting potentially protective but also deleterious effects. OBJECTIVE: Our main objective was to investigate the prospective association between dietary folate intake and risks of skin cancer (overall), nonmelanoma skin cancer (NMSC), and basal cell carcinoma (BCC). As an exploratory analysis, we also investigated the prospective association between erythrocyte folate concentration and skin cancer risk. DESIGN: In this study, we included 5880 participants in the Supplémentation en Vitamines et Minéraux Antioxydants (SU.VI.MAX) cohort (follow-up: 1994-2007) who completed at least six 24-h dietary records during the first 2 y of the study. Associations between sex-specific tertiles of dietary and erythrocyte folate and skin cancer risk were assessed by using multivariate Cox proportional hazards models. RESULTS: After a median follow-up of 12.6 y, 144 incident skin cancers were diagnosed. Dietary folate intake was associated with increased risk of overall skin cancer [HR for tertile 3 compared with tertile 1 (HR(T3vs.T1)): 1.79; 95% CI: 1.07, 2.99; P-trend = 0.03], NMSC (HR(T3vs.T1): 1.85; 95% CI: 1.06, 3.23; P-trend = 0.03), and BCC (HR(T3vs.T1): 1.78; 0.98, 3.24; P-trend = 0.05). This association was observed in women (corresponding P-trend = 0.007, 0.009, and 0.009, respectively) but not in men (P-trend = 0.8, 0.8, and 0.9, respectively). P-interaction values between tertiles of dietary folate intake and sex were 0.04, 0.02, and 0.02 for overall skin cancer, NMSC, and BCC, respectively. Erythrocyte folate concentration was directly associated with increased risk of overall skin cancer (HR(T3vs.T1): 2.54; 95% CI: 0.95, 6.81; P-trend = 0.03), NMSC (HR(T3vs.T1): 3.49; 95% CI: 1.11, 11.0; P-trend = 0.01), and BCC (HR(T3vs.T1): 7.44; 95% CI: 1.57, 35.3; P-trend = 0.004) (men and women combined). CONCLUSIONS: This prospective study suggests an association between dietary folate intake and erythrocyte folate concentration and increased risk of overall skin cancer, NMSC, and BCC. Although several mechanistic hypotheses and 2 previous large prospective studies on BCC are in line with these results, epidemiologic literature is limited, and future research is needed to better elucidate the potential role of folate in the cause of skin cancers.

Sentinel node status and immunosuppression: recurrence factors in localized Merkel cell carcinoma.

The prognostic value of the sentinel lymph node in Merkel cell carcinoma (MCC) has been examined previously in heterogeneous retrospective studies. The current retrospective study included a homogeneous population of patients with a localized MCC, all staged with sentinel lymph node biopsy. Factors associated with 3-year progression-free survival were analysed using logistic regression. The sentinel lymph node was positive in 32% of patients. The recurrence rate was 26.9%. In first analyses (n = 108), gender (p = 0.0115) and the presence of immunosuppression (p = 0.0494) were the only significant independent factors. In further analyses (n = 80), excluding patients treated with regional radiotherapy, sentinel lymph node status was the only significant prognostic factor (p = 0.0281). Immunosuppression and positive sentinel lymph node are associated with a worse prognosis in patients with MCC. Nodal irradiation impacts on the prognostic value of the sentinel lymph node status.

Combined ablation and resection (CARe) as an effective parenchymal sparing treatment for extensive colorectal liver metastases.

BACKGROUND: Combined intra-operative ablation and resection (CARe) is proposed to treat extensive colorectal liver metastases (CLM). This multicenter study was conducted to evaluate overall survival (OS), local recurrence-free survival (LRFS), hepatic recurrence-free survival (HRFS) and progression-free survival (PFS), to identify factors associated with survival, and to report complications. MATERIALS AND METHODS: Four centers combined retropectively their clinical experiences regarding CLM treated by CARe. CLM characteristics, pre- and post-operative chemotherapy regimens, surgical procedures, complications and survivals were analyzed. RESULTS: Of the 288 patients who received CARe, 210 (73%) had synchronous and 255 (88%) had bilateral CLM. Twenty-two patients (8%) had extrahepatic disease. Median follow-up was 3.17 years (95%CI 2.83-4.08). Median OS was 3.33 years (95%CI 3.08-4.17) and 5-year OS was 37% (95%CI 29-45). One- and 5-year LRFS from ablated lesions were 87.9% (95%CI 83.3-91.2) and 78.0% (95%CI 71-83), respectively. Median HRFS and PFS were 14 months (95%CI 11-18) and 9 months (95%CI 8-11), respectively. One hundred patients experienced complications: 29 grade I, 68 grade II-III-IV, and three deaths. In the multivariate models adjusted for center, the occurrence of complications was confirmed as a major independent factor associated with 3-year OS (HR 1.80; P = 0.008). Five-year OS was 25.6% (95%CI 14.9-37.6) for patients with complications and 45% (95%CI 33.3-53.4) for patients without. CONCLUSIONS: Recent strategies facing advanced CLM include non-anatomic resections, portal-induced hypertrophy of the future remnant liver and aggressive medical preoperative treatments. CARe has the qualities of an approach that allows effective tumor clearance while maintaining good tolerance for the patient.

Clinical phenotype of scabies by age.

OBJECTIVE: Scabies has a clinical presentation that seems to vary according to age. We conducted a prospective study with the goal of delineating the clinical presentation of the disease into 3 groups of age: infants, <2 years; children, 2 to 15 years; and adults, >15 years. METHODS: This trial was a prospective, multicenter observational study in consecutive patients with a confirmed diagnosis of scabies who were seen in 13 French Departments of Dermatology and Pediatric Dermatology between April 2010 and April 2011. A standardized questionnaire was completed for each patient. To identify factors associated with patient age, comparisons between the 3 age groups were conducted by using univariate and multivariate multinomial logistic regression analyses. RESULTS: A total of 323 individuals were included; the gender ratio (female:male) was 1.2:1. In univariate analysis, infants were more likely to have facial involvement. In multivariate logistic regression, relapse was more frequent in children (odds ratio [OR]: 2.45 [95% confidence interval (CI):1.23-4.88]) and infants (OR: 3.26 [95% CI: 1.38-7.71]). In addition, family members with itch (OR: 2.47 [95% CI: 1.04-5.89]), plantar (OR: 20.57 [95% CI: 7.22-58.60]), and scalp (OR: 16.94 [95% CI: 3.70-77.51]) involvement were also found to be independently associated with the age group <2 years. CONCLUSIONS: There is a specific clinical presentation of scabies in infants and children. Taking into account these specificities may be helpful for the early diagnosis and the identification of cases to prevent the propagation of the disease.

Outcome after implantation of a cardioverter-defibrillator in patients with Brugada syndrome: a multicenter study-part 2.

BACKGROUND: Implantable cardioverter-defibrillator indications in Brugada syndrome remain controversial, especially in asymptomatic patients. Previous outcome data are limited by relatively small numbers of patients or short follow-up durations. We report the outcome of patients with Brugada syndrome implanted with an implantable cardioverter-defibrillator in a large multicenter registry. METHODS AND RESULTS: A total of 378 patients (310 male; age, 46±13 years) with a type 1 Brugada ECG pattern implanted with an implantable cardioverter-defibrillator (31 for aborted sudden cardiac arrest, 181 for syncope, and 166 asymptomatic) were included. Fifteen patients (4%) were lost to follow-up. During a mean follow-up of 77±42 months, 7 patients (2%) died (1 as a result of an inappropriate shock), and 46 patients (12%) had appropriate device therapy (5±5 shocks per patient). Appropriate device therapy rates at 10 years were 48% for patients whose implantable cardioverter-defibrillator indication was aborted sudden cardiac arrest, 19% for those whose indication was syncope, and 12% for the patients who were asymptomatic at implantation. At 10 years, rates of inappropriate shock and lead failure were 37% and 29%, respectively. Inappropriate shock occurred in 91 patients (24%; 4±4 shocks per patient) because of lead failure (n=38), supraventricular tachycardia (n=20), T-wave oversensing (n=14), or sinus tachycardia (n=12). Importantly, introduction of remote monitoring, programming a high single ventricular fibrillation zone (>210-220 bpm), and a long detection time were associated with a reduced risk of inappropriate shock. CONCLUSIONS: Appropriate therapies are more prevalent in symptomatic Brugada syndrome patients but are not insignificant in asymptomatic patients (1%/y). Optimal implantable cardioverter-defibrillator programming and follow-up dramatically reduce inappropriate shock. However, lead failure remains a major problem in this population.

Development and validation of the K-VSCOR for scoring Koebner's phenomenon in vitiligo/non-segmental vitiligo.

The relation of vitiligo/non-segmental vitiligo (NSV) to Koebner's phenomenon is variably appreciated. Our objective was to develop and validate a simple clinical score for Koebner's phenomenon (KP) in patients with vitiligo/NSV. The study population was composed of 351 individuals in the development sample and 285 patients in the validation sample. Seven variables were independently associated with the presence of KP: disease duration of more than 3 yr, forehead + scalp areas, eyelids, wrists, genital + belt areas, knees and tibial crests. The score computed by the weighted sum of the rounded coefficients of these seven variables ranged from 0 to 56 (mean 38.39 ± 22.93). The probability of having KP was computed as follows: exp (-2.37 + 0.1*score)/exp [1 + (-2.37 + 0.1*score)]. When applying the score to each patient in the validation and the development sample, the score maintained adequate discrimination and calibration (AUC-ROC = 0.78), arguing that KP can be adequately predicted using our score. Further studies should evaluate KP assessed by the K-VSCOR in clinical practice with the aim to determine its association with clinical profile, course and treatment response of vitiligo.

Halo nevi association in nonsegmental vitiligo affects age at onset and depigmentation pattern.

OBJECTIVE: To compare factors associated with halo nevi with nonsegmental vitiligo (NSV) vs NSV alone. DESIGN: Prospective observational study in 553 patients with a confirmed diagnosis of NSV attending a vitiligo clinic between January 1, 2006, and July 1, 2010. SETTING: Vitiligo Clinic at the Department of Dermatology, University Hospital Center of Bordeaux, Bordeaux, France. PATIENTS: The Vitiligo European Task Force questionnaire was informed for each patient attending the clinic with a confirmed diagnosis of NSV after the exclusion of other forms of vitiligo (focal, mucosal, and not classifiable). Thyroid function and antithyroid antibodies were screened if not obtained in the previous year. MAIN OUTCOME MEASURES: Extent of disease and markers of autoimmunity or autoinflammation. RESULTS: Of the 553 patients, 130 had halo nevi-NSV and 423 had NSV. Family history of premature hair graying (odds ratio, 1.74; P < .01) was positively associated with halo nevi-NSV by univariate analysis. Using multivariate analysis, age at onset younger than 18 years, phototype, total body area, localization on the trunk, involvement of hands and feet, and total staging were found to be independent factors. Age at onset younger than 18 years; phototypes I, II, and III; trunk involvement; and staging were positively associated with halo nevi-NSV, whereas this association was negative for total affected area and involvement of hands and feet. CONCLUSIONS: Halo nevi association in NSV affects age at onset and depigmentation pattern and has a stronger link with familial premature hair graying, suggesting that premature hair graying may involve, at least partly, an autoimmune pathway.

Surgery improves pain, function and quality of life in patients with spinal metastases: a prospective study on 118 patients.

PURPOSE: There are few prospective studies on surgical outcomes and survival in patients with metastatic disease to the spine. The magnitude and duration of effect of surgery on pain relief and quality of life remains uncertain. Therefore, the aim of this clinical study was to prospectively evaluate clinical, functional, quality of life and survival outcomes after palliative surgery for vertebral metastases. METHODS: 118 consecutive patients who underwent spinal surgery for symptomatic vertebral metastases were prospectively followed up for 12 months or until death. Clinical data and data from the European Organization for Research and Treatment of Cancer (EORTC) QLQ-C30 questionnaire were obtained pre- and post-operatively and at regular follow-up intervals. RESULTS: Surgery was effective in achieving rapid improvement in axial and radicular pain, neurological deficit, sphincteric dysfunction and ambulatory status, with a complication rate of 26% and a 12 month mortality rate of 48%. Almost 50% of patients had complete resolution of back pain, radiculopathy and neurological deficit. Of the patients who were non-ambulant and incontinent, over 50% regained ambulatory ability and recovered urinary continence. The overall incidence of wound infection or breakdown was 6.8% and the local recurrence rate was 8.5%. There was a highly significant improvement in physical, role, cognitive and emotional functioning and global health status post-operatively. Greatest improvement in pain, function and overall quality of life occurred in the early post-operative period and was maintained until death or during the 12 month prospective follow-up period. CONCLUSION: The potential for immediate and prolonged improvement in pain, function and quality of life in patients with symptomatic vertebral metastases should be considered during the decision-making process when selecting and counselling patients for surgery.

Survival prognostic factors and clinical outcomes in patients with spinal metastases.

PURPOSE: In patients with metastatic disease to the spine, patient selection for surgery and the extent of surgery to perform thereafter remains controversial, with the patient's survival prognosis the most important consideration. For this reason, we conducted a prospective study investigating prognostic factors and clinical outcomes in a consecutive series of patients with vertebral metastases. METHODS: A total of 142 consecutive patients with vertebral metastases referred to us for consideration of surgery were prospectively enrolled into this study. Of these, 118 patients subsequently underwent palliative surgery for intractable pain or radiculopathy, bony instability or spinal cord compression. Patients were followed up for 12 months or until death. A multivariate analysis of the patients was conducted using the Cox proportional hazards model. The survival predictive accuracy of the Tokuhashi score was also investigated. For the patients who underwent surgery, pre- and post-operative outcomes were assessed on pain, neurological deficit, function and overall quality of life. RESULTS: The overall 12-month mortality rate was 50.7% and the median survival was 5 months. Multivariate analysis showed that independent prognostic factors for survival after spinal metastases include primary tumour type, Karnofsky functional status, ASA score and pain. Neither the original nor revised Tokuhashi scores were reliable in predicting survival in our European population. In the patients who underwent operative intervention, there was an immediate and prolonged improvement in pain, neurological deficit, function and quality of life in the majority of cases. CONCLUSIONS: The potential for rapid and maintained improvement in clinical outcome and quality of life should be considered when selecting patients with metastatic disease to the spine for surgery rather than basing decisions solely on survival prognostic factors comprising current scoring systems.