Bootstrap-based procedures for inference in nonparametric receiver-operating characteristic curve regression analysis.

Prior to using a diagnostic test in a routine clinical setting, the rigorous evaluation of its diagnostic accuracy is essential. The receiver-operating characteristic curve is the measure of accuracy most widely used for continuous diagnostic tests. However, the possible impact of extra information about the patient (or even the environment) on diagnostic accuracy also needs to be assessed. In this paper, we focus on an estimator for the covariate-specific receiver-operating characteristic curve based on direct regression modelling and nonparametric smoothing techniques. This approach defines the class of generalised additive models for the receiver-operating characteristic curve. The main aim of the paper is to offer new inferential procedures for testing the effect of covariates on the conditional receiver-operating characteristic curve within the above-mentioned class. Specifically, two different bootstrap-based tests are suggested to check (a) the possible effect of continuous covariates on the receiver-operating characteristic curve and (b) the presence of factor-by-curve interaction terms. The validity of the proposed bootstrap-based procedures is supported by simulations. To facilitate the application of these new procedures in practice, an R-package, known as npROCRegression, is provided and briefly described. Finally, data derived from a computer-aided diagnostic system for the automatic detection of tumour masses in breast cancer is analysed.

Assessment of morbidity in gynaecologic oncology laparoscopy and identification of possible risk factors.

BACKGROUND: The aim of this study was to ascertain the incidence of and the risk factors associated with morbidity in laparoscopy performed on patients with cervical cancer and endometrial cancer. METHODS: This was an observational study of a cohort of 128 women, 89 with endometrial cancer and 39 with cervical cancer from January 2000 to December 2011. We used the Student's t-test or the Mann-Whitney U test for continuous variables, and the Chi-square or Fisher's exact test for categorical variables. RESULTS: Complications were found in 44 patients (34.4%). After a multivariate analysis, among the risk factors associated with the presence of complications as the only type of surgery was found to be statistically significant (p = 0.043), more frequent in the most complex procedures such as Wertheim operation, trachelectomy, and para-aortic lymphadenectomy. Type of surgery (p = 0.003) and tumour type (p = 0.003) were risk factors associated with conversion to laparotomy. It was more frequent among the most complex procedures and cervical cancer cases. Regarding the need for transfusion, significant differences were observed in terms of surgery duration (p < 0.001), more frequent in longer surgery. CONCLUSION: Morbidity in laparoscopic surgical oncology is related to the surgery complexity, where the basal characteristics of the patient are not a factor of influence in the development of complications.

ME20-S as a Potential Biomarker for the Evaluation of Uveal Melanoma.

PURPOSE: We previously identified the presence of the melanocyte-specific secreted (ME20-S) glycoprotein in secretomes of uveal melanoma (UM) cultures. The aim of this study was to test for the presence and levels of ME20-S in the serum of patients with choroidal nevi and UM and correlate these levels with individual clinical data. METHODS: Serum ME20-S levels were determined by ELISA in 111 patients distributed into four categories (53 choroidal nevi, 30 untreated UM, 11 10-year disease-free [DF] UM, 17 hepatic metastatic UM) and 32 age- and sex-matched controls. ME20-S levels were correlated with individual clinical data. RESULTS: The UM and the metastatic groups showed significantly higher levels of serum ME20-S than the other groups (P < 0.001). ME20-S levels in the DF patients did not differ from those in the control group. In addition, log-transformed serum ME20-S levels showed a positive correlation with the thickness of the lesion mass in UM patients (regression coefficient 0.0689, 95% confidence interval 0.0689-0.1123, R2 = 27.1%). CONCLUSIONS: Elevated ME20-S serum levels are associated with tumor size and advanced stages of UM while low levels are characteristic of DF patients. ME20-S might be a promising serum marker for UM and useful for monitoring metastatic disease.

Serum DJ-1/PARK 7 is a potential biomarker of choroidal nevi transformation.

PURPOSE: There is substantial evidence that intraocular melanomas arise from benign nevi in the uveal tract. Previous studies performed by the authors revealed that uveal melanoma cells secrete the oncoprotein DJ-1/PARK7 into the extracellular environment and circulation. The aim of this study was to determine whether circulating DJ-1 serum levels correlate with known clinical risk factors of nevi growth. METHODS: Standardized ultrasonography, optical coherence tomography, and eye fundus examinations were used to evaluate the clinical risk factors of nevi growth. These clinical risk factors (including nevi size, distance of margins to the optic disc, detection of acoustic hollowness, presence of ocular symptoms, orange pigment, subretinal fluid, and absence of drusen) were examined in 53 consecutive patients from January 2009 to February 2011. Serum levels of DJ-1/PARK7 in these patients and in healthy age- and sex-matched controls (n = 32) were analyzed using ELISA. RESULTS: Within the choroidal nevi group, DJ-1 serum levels were higher in those with symptoms (P < 0.033), with a nevus thickness greater than 1.5 mm (P < 0.001), a large basal diameter greater than 8 mm (P < 0.001), and the presence of acoustic hollowness (P < 0.001), compared to those patients without these risk factors. Similar significant differences were found when these at risk nevi subgroups were compared to healthy persons. CONCLUSIONS: Elevated serum levels of DJ-1 are associated with choroidal nevi transformation risk factors. Therefore, DJ-1 appears to be a promising factor for predicting the growth of choroidal nevi and may be a potential biomarker of malignancy.