Plasma soluble fms-like tyrosine kinase 1 to placental growth factor ratio of 11.5 multiples of median predicts preeclampsia with severe features within 2 weeks of testing.

BACKGROUND: Angiogenic imbalances, characterized by an excess of antiangiogenic factors (soluble fms-like tyrosine kinase 1) and reduced angiogenic factors (vascular endothelial growth factor and placental growth factor), contribute to the mechanisms of disease in preeclampsia. The ratio of soluble fms-like tyrosine kinase 1 to placental growth factor has been used as a biomarker for preeclampsia, but the cutoff values may vary with gestational age and assay platform. OBJECTIVE: This study aimed to compare multiples of the median of the maternal plasma soluble fms-like tyrosine kinase 1 to placental growth factor ratio, soluble fms-like tyrosine kinase 1, placental growth factor, and conventional clinical and laboratory values in their ability to predict preeclampsia with severe features. STUDY DESIGN: We conducted a cohort study across 18 United States centers involving hospitalized individuals with hypertension between 23 and 35 weeks' gestation. Receiver operating characteristic curve analyses of maternal plasma biomarkers, highest systolic or diastolic blood pressures, and laboratory values at enrollment were performed for the prediction of preeclampsia with severe features. The areas under the curve were compared, and quasi-Poisson regression models were fitted to estimate relative risks. The primary outcome was preeclampsia with severe features within 2 weeks of enrollment. Secondary outcomes were a composite of severe adverse maternal outcomes (elevated liver enzymes, low platelets count, placental abruption, eclampsia, disseminated intravascular coagulation, and pulmonary edema) and a composite of severe adverse perinatal outcomes (birth weight below the third percentile, very preterm birth [<32 weeks' gestation], and fetal or neonatal death). RESULTS: Of the 543 individuals included in the study, preeclampsia with severe features within 2 weeks was observed in 33.1% (n=180) of them. A receiver operating characteristic curve-derived cutoff of 11.5 multiples of the median for the soluble fms-like tyrosine kinase 1 to placental growth factor plasma ratio provided good sensitivity (90.6%), specificity (76.9%), positive predictive value (66.0%), negative predictive value (94.3%), positive likelihood ratio (3.91), negative likelihood ratio (0.12), and accuracy (81.4%) for preeclampsia with severe features within 2 weeks. This cutoff was used to compare test positive cases (≥ cutoff) and test negative cases (< cutoff). Preeclampsia with severe features (66.0% vs 5.7%; P<.001) and composites of severe adverse maternal (8.11% vs 2.7%; P=.006) or perinatal (41.3% vs 10.14%; P=.001) outcomes within 2 weeks were more frequent in test positive cases than in test negative cases. A soluble fms-like tyrosine kinase 1 to placental growth factor plasma ratio ≥11.5 multiples of the median was independently associated with preeclampsia with severe features (adjusted incidence rate ratio, 9.08; 95% confidence interval, 6.11-14.06; P<.001) and a composite of severe adverse perinatal outcomes (adjusted incidence rate ratio, 9.42; 95% confidence interval, 6.36-14.53; P<.001) but not with a composite of severe adverse maternal outcomes (adjusted incidence rate ratio, 2.20; 95% confidence interval, 0.95-5.54; P=.08). The area under the curve for the soluble fms-like tyrosine kinase 1 to placental growth factor plasma ratio in multiples of the median (0.91; 95% confidence interval, 0.89-0.94) for preeclampsia with severe features within 2 weeks was significantly higher (P<.001 for all comparisons) than either plasma biomarker alone or any other parameter with the exception of absolute soluble fms-like tyrosine kinase 1 to placental growth factor plasma ratio values. CONCLUSION: A soluble fms-like tyrosine kinase 1 to placental growth factor plasma ratio ≥11.5 multiples of the mean among hospitalized patients with hypertension between 23 and 35 week's gestation predicts progression to preeclampsia with severe features and severe adverse perinatal outcomes within 2 weeks.

Variations in surgical practice and short-term outcomes for degenerative lumbar scoliosis and spondylolisthesis: do surgeon training and experience matter?

For diverse procedures, sizable geographic variation exists in rates and outcomes of surgery, including for degenerative lumbar spine conditions. Little is known about how surgeon training and experience are associated with surgeon-level variations in spine surgery practice and short-term outcomes. This retrospective observational analysis characterized variations in surgical operations for degenerative lumbar scoliosis or spondylolisthesis, two common age-related conditions. The study setting was two large spine surgery centers in one region during 2017-19. Using data (International Classification of Diseases-10th edition and current procedural terminology codes) extracted from electronic health record systems, we characterized surgeon-level variations in practice (use of instrumented fusion - a more extensive procedure that involves device-related risks) and short-term postoperative outcomes (major in-hospital complications and readmissions). Next, we tested for associations between surgeon training (specialty and spine fellowship) and experience (career stage and operative volume) and use of instrumented fusion as well as outcomes. Eighty-nine surgeons performed 2481 eligible operations. For the study diagnoses, spine surgeons exhibited substantial variation in operative volume, use of instrumented fusion, and postoperative outcomes. Among surgeons above the median operative volume, use of instrumented fusion ranged from 0% to >90% for scoliosis and 9% to 100% for spondylolisthesis, while rates of major in-hospital complications ranged from 0% to 25% for scoliosis and from 0% to 14% for spondylolisthesis. For scoliosis, orthopedic surgeons were more likely than neurosurgeons to perform instrumented fusion for scoliosis [49% vs. 33%, odds ratio (OR) = 2.3, 95% confidence interval (95% CI) 1.3-4.2, P-value = .006] as were fellowship-trained surgeons (49% vs. 25%, OR = 3.0, 95% CI 1.6-5.8; P = .001). Fellowship-trained surgeons had lower readmission rates. Surgeons with higher operative volumes used instrumented fusion more often (OR = 1.1, 95% CI 1.0-1.2, P < .05 for both diagnoses) and had lower rates of major in-hospital complications (OR = 0.91, 95% CI 0.85-0.97; P = .006). Surgical practice can vary greatly for degenerative spine conditions, even within the same region and among colleagues at the same institution. Surgical specialty and subspecialty, in addition to recent operative volume, can be linked to variations in spine surgeons' practice patterns and outcomes. These findings reinforce the notion that residency and fellowship training may contribute to variation and present important opportunities to optimize surgical practice over the course of surgeons' careers. Future efforts to reduce unexplained variation in surgical practice could test interventions focused on graduate medical education. Graphical Abstract.

Systemic immune mediators reflect tumour-infiltrating lymphocyte intensity and predict therapeutic response in triple-negative breast cancer.

Triple-negative breast cancer (TNBC) is an aggressive form of breast cancer (BC). Neoadjuvant chemotherapy has proven efficacy in its treatment, and a pathological complete response (pCR) to therapy is predictive of improved long-term survival. The immune response is key to successful neoadjuvant chemotherapy, as indicated by the relation between the percentage of stromal tumour-infiltrating lymphocytes (TILs) in pre-treated tumour tissue samples and the likelihood of achieving pCR. Here we studied systemic immune mediators from volunteer TNBC patients before undergoing neoadjuvant chemotherapy to determine the systemic response association with TIL intensity, treatment response and survival. Patients were classified into pCR responder or non-responder at time of surgery. We found higher levels of immune mediators before treatment began in patients that went on to be pCR responders versus non-pCR, with area under the curve (AUC) values of 0.64-0.80. We also observed a positive correlation between inflammatory systemic immune mediators and the percentage of TILs in pCR responder patients. Combining TILs and systemic immune mediator levels provided stronger AUC values (range of 0.72-0.82). Last, performing a progression-free survival analysis with several of the systemic cytokines that predict pCR, segregated the patients into long- and short-survival groups based on high and low production of the cytokines, respectively. Our study demonstrates that circulating cytokines, before treatment begins, predict pCR in TNBC patients treated with neoadjuvant chemotherapy. Moreover, they may act as a surrogate marker of high TILs or together with TILs to better predict pCR and survival.

Intraoperative radiotherapy for brain metastases: first-stage results of a single-arm, open-label, phase 2 trial.

OBJECTIVE: Focal stereotactic radiosurgery to the surgical cavity lowers local recurrence after resection of brain metastases (BM). To evaluate local control (LC) and brain disease control (BDC) after intraoperative radiotherapy (IORT) for resected BM. METHODS: Adult patients with completely resected single supratentorial BM were recruited and underwent IORT to the cavity with a prescribed dose of 18 Gy to 1 mm-depth. Primary endpoints were actuarial LC and BDC. Local failure (LF) and distant brain failure (DBF), with death as a competing risk, were estimated. Secondary endpoints were overall survival (OS) and incidence of radiation necrosis (RN). Simon's two-stage design was used and estimated an accrual of 10 patients for the first-stage analysis and a LC higher than 63% to proceed to second stage. We report the final analysis of the first stage. RESULTS: Between June 2019 to November 2020, 10 patients were accrued. Median clinical and imaging FU was 11.2 and 9.7 months, respectively. Median LC was not reached and median BDC was 5 months. The 6-month and 12-month LC was 87.5%. The 6-month and 12-month BDC was 39% and 13%, respectively. Incidence of LF at 6 and 12 months was 10% and of DBF at 6 and 12 months was 50% and 70%, respectively. Median OS was not reached. The 6-month and 12-month OS was 80%. One patient had asymptomatic RN. CONCLUSION: IORT for completely resected BM is associated with a potential high local control and low risk of RN, reaching the pre-specified criteria to proceed to second stage and warranting further studies.

Simulation study comparing analytical methods for single-item longitudinal patient-reported outcomes data.

PURPOSE: Efficient analytical methods are necessary to make reproducible inferences on single-item longitudinal ordinal patient-reported outcome (PRO) data. A thorough simulation study was performed to compare the performance of the semiparametric probabilistic index models (PIM) with a longitudinal analysis using parametric cumulative logit mixed models (CLMM). METHODS: In the setting of a control and intervention arm, we compared the power of the PIM and CLMM to detect differences in PRO adverse event (AE) between these groups using several existing and novel summary scores of PROs. For each scenario, PRO data were simulated using copula multinomial models. Comparisons were also exemplified using clinical trial data. RESULTS: On average, CLMM provided substantially greater power than the PIM to detect differences in PRO-AEs between the groups when the baseline-adjusted method was used, and a small advantage in power when using the baseline symptom as a covariate. CONCLUSION: Although the CLMM showed the best performance among analytical methods, it relies on assumptions difficult to verify and that might not be fulfilled in the real world, therefore our recommendation is the use of PIM models with baseline symptom as a covariate.

Does the Addition of Mutations of CTNNB1 S45F to Clinical Factors Allow Prediction of Local Recurrence in Patients With a Desmoid Tumor? A Local Recurrence Risk Model.

BACKGROUND: The initial approach to the treatment of desmoid tumors has changed from surgical resection to watchful waiting. However, surgery is still sometimes considered for some patients, and it is likely that a few patients would benefit from tumor removal if the likelihood of local recurrence could be predicted. However, to our knowledge, there is no tool that can provide guidance on this for clinicians at the point of care. QUESTION/PURPOSE: We sought to explore whether a combined molecular and clinical prognostic model for relapse in patients with desmoid tumors treated with surgery would allow us to identify patients who might do well with surgical excision. METHODS: This was a retrospective, single-center study of 107 patients with desmoid tumors who were surgically treated between January 1980 and December 2015, with a median follow-up of 106 months (range 7 to 337 months). We correlated clinical variables (age, tumor size, and localization) and CTNNB1 gene mutations with recurrence-free survival. Recurrence-free survival was estimated using a Kaplan-Meier curve. Univariate and multivariable analyses of time to local recurrence were performed using Cox regression models. A final nomogram model was constructed according to the final fitted Cox model. The predictive performance of the model was evaluated using measures of calibration and discrimination: calibration plot and the Harrell C-statistic, also known as the concordance index, in which values near 0.5 represent a random prediction and values near 1 represent the best model predictions. RESULTS: The multivariable analysis showed that S45F mutations (hazard ratio 5.25 [95% confidence interval 2.27 to 12.15]; p < 0.001) and tumor in the extremities (HR 3.15 [95% CI 1.35 to 7.33]; p = 0.008) were associated with a higher risk of local recurrence. Based on these risk factors, we created a model; we observed that patients considered to be at high risk of local recurrence as defined by having one or two factors associated with recurrence (extremity tumors and S45F mutation) had an HR of 8.4 compared with patients who had no such factors (95% CI 2.84 to 24.6; p < 0.001). From these data and based on the multivariable Cox models, we also developed a nomogram to estimate the individual risk of relapse after surgical resection. The model had a concordance index of 0.75, or moderate discrimination. CONCLUSION: CTNNB1 S45F mutations combined with other clinical variables are a potential prognostic biomarker associated with the risk of relapse in patients with desmoid tumors. The developed nomogram is simple to use and, if validated, could be incorporated into clinical practice to identify patients at high risk of relapse among patients opting for surgical excision and thus help clinicians and patients in decision-making. A large multicenter study is necessary to validate our model and explore its applicability. LEVEL OF EVIDENCE: Level III, therapeutic study.

Sex with animals among men attended in referral centers for sexually transmitted infections in northeast Brazil: prevalence, associated factors and behavioral aspects.

PURPOSE: Our objective was to investigate the prevalence of SWA, associated factors, relationship with STIs, and behavioral aspects in men attended at Referral Centers for STIs and acquired immunodeficiency syndrome (AIDS)/CR-STI/AIDS in northeast Brazil. MATERIALS AND METHODS: In this cross-sectional study, a questionnaire with sociodemographic, clinical, sexual and SWA practices information was applied to 400 men attended at two CR-STI/AIDS in Northeast Brazil on the years of 2018 and 2019. Clinical and laboratory diagnoses of STIs were confirmed in medical records. Logistic regression models were performed to identify the independent predictors for SWA. RESULTS: The prevalence of SWA over total samples was 15.00%. Of the participants, 239 (59.75%) of the participants were diagnosed with STIs, and of these 37 (15.48%) reported SWA. Most men practiced SWA in adolescence, being the last episode more than 20 years ago, usually with asinine and mules, in vaginal route and without a condom. SWA practitioners have higher percentages of occurrence of some viral STIs. SWA was associated with increasing age, history of residence in a rural area with remained over 12 years, married or widowed/separated, heterosexuals, with less than 7 years of study, Catholics, with hepatitis B, former user of alcoholic beverages and smokers, with a history of STI and intercourse with sex workers. CONCLUSION: SWA practices increase STIs vulnerability. The association between hepatitis B and SWA highlights the importance of educational campaigns and conclusive studies on the topic.

A general class of promotion time cure rate models with a new biological interpretation.

Over the last decades, the challenges in survival models have been changing considerably and full probabilistic modeling is crucial in many medical applications. Motivated from a new biological interpretation of cancer metastasis, we introduce a general method for obtaining more flexible cure rate models. The proposal model extended the promotion time cure rate model. Furthermore, it includes several well-known models as special cases and defines many new special models. We derive several properties of the hazard function for the proposed model and establish mathematical relationships with the promotion time cure rate model. We consider a frequentist approach to perform inferences, and the maximum likelihood method is employed to estimate the model parameters. Simulation studies are conducted to evaluate its performance with a discussion of the obtained results. A real dataset from population-based study of incident cases of melanoma diagnosed in the state of São Paulo, Brazil, is discussed in detail.

The Relationship between Lifetime Exposure to Potentially Traumatic Events, Peritraumatic Dissociation, and PTSD in a Sample of Sexually Assaulted Women in Sao Paulo, Brazil.

Sexually assaulted women represent a particularly high-risk group for developing post-traumatic stress disorder (PTSD). Potentially traumatic events (PTEs) and peritraumatic dissociation (PD) are known risk factors for PTSD. However, little is known about how previous trauma affects PD and how this relationship affects PTSD. We aimed to investigate whether PD acts as a mediator between PTEs and PTSD severity in a sample of recently sexually assaulted women in Sao Paulo, Brazil. Seventy-four sexually assaulted women aged 18-44 completed questionnaires and structured interviews on PTSD, PD, and PTEs. We examined direct and indirect effects of variables using causal mediation analysis. Lifetime exposure to PTEs was a risk factor for PD, but PD was not a risk factor for PTSD symptom severity. Also, PD was not a mediator between PTEs and PTSD severity. We provided recommendations on how to further explore the relationship between lifetime traumatic exposure, PTSD, and peritraumatic dissociation.

Endoscopic assessment of radiological stage IVA cervical cancer: A bivariate meta-analysis supporting an evidence-based staging algorithm proposal.

OBJECTIVE: To optimize the use of confirmatory endoscopic exams (cystoscopy/proctoscopy) in the staging of locally advanced cervical cancer (LACC), the present study evaluates the predictive value of radiological exams (CT and MRI) to detect bladder/rectum invasion. METHODS: A systematic search of databases (PubMed and EMBASE) was performed (CRD42021270329). The inclusion criteria were: a) cervix cancer diagnosis; b) staging CT and/or MRI (index test); c) staging cystoscopy and/or proctoscopy (standard test); and d) numbers of true positives (TP), true negatives (TN), false positives (FP), and false negatives (FN) provided. A random-effects bivariate meta-analysis of positive predictive value (PPV) and negative predictive value (NPV) was performed with moderator analyses by imaging modality (CT and MRI) and prevalence. RESULTS: Nineteen studies met the inclusion criteria, totaling 3480 and 1641 patients for bladder and rectum analyses, respectively. For bladder invasion (prevalence ranged from 0.9% to 34.5%), the overall PPV was 45% (95% confidence interval, 33%-57%, based on 19 studies). Per subgroup, the PPV was 31% for MRI/prevalence ≤6%, 33% for CT/prevalence ≤6%, and 69% for CT/prevalence >6%. For rectal invasion (prevalence ranged from 0.4% to 20.0%), the overall PPV was 30% (95% confidence interval, 17%-47%, based on 8 studies). Per subgroup, the PPV was 36% for MRI/prevalence ≤1%, 17% for MRI/prevalence >1%, and 38% for CT/prevalence >1%. The overall NPV for bladder invasion and rectal invasion were 98% (95% confidence interval, 97%-99%) and 100% (95% confidence interval, 99%-100%), respectively. Considering prevalence and radiological modality, the point estimate of NPV varied from 95% to 100% for bladder invasion and from 99% to 100% for rectum invasion. CONCLUSIONS: Due to low PPV (<50%) of radiological staging, endoscopic exams may be necessary to correctly assess radiological stage IVA LACC. However, they are not necessary after negative radiological exam (NPV ≥95%).

Nonproportional hazards model with a frailty term for modeling subgroups with evidence of long-term survivors: Application to a lung cancer dataset.

With advancements in medical treatments for cancer, an increase in the life expectancy of patients undergoing new treatments is expected. Consequently, the field of statistics has evolved to present increasingly flexible models to explain such results better. In this paper, we present a lung cancer dataset with some covariates that exhibit nonproportional hazards (NPHs). Besides, the presence of long-term survivors is observed in subgroups. The proposed modeling is based on the generalized time-dependent logistic model with each subgroup's effect time and a random term effect (frailty). In practice, essential covariates are not observed for several reasons. In this context, frailty models are useful in modeling to quantify the amount of unobservable heterogeneity. The frailty distribution adopted was the weighted Lindley distribution, which has several interesting properties, such as the Laplace transform function on closed form, flexibility in the probability density function, among others. The proposed model allows for NPHs and long-term survivors in subgroups. Parameter estimation was performed using the maximum likelihood method, and Monte Carlo simulation studies were conducted to evaluate the estimators' performance. We exemplify this model's use by applying data of patients diagnosed with lung cancer in the state of São Paulo, Brazil.

Prognostic value of response evaluation based on breast MRI after neoadjuvant treatment: a retrospective cohort study.

OBJECTIVE: To investigate the impact of response evaluation after neoadjuvant chemotherapy (NAC) in breast cancer patients, assessed by both magnetic resonance imaging (MRI) and pathology, on disease-free survival (DFS). METHODS: This single-center, retrospective cohort study included consecutive breast cancer patients who underwent NAC and preoperative breast MRI. Resolution of invasive carcinoma in the breast and axilla was defined as complete pathological response (pCR). Radiological complete response (rCR) was defined as the absence of abnormal enhancement in the tumor site. Kaplan-Meier estimator was used to estimate the disease-free survival on 60 months. Cox regression analysis was used to estimate hazard ratio (HR) values. RESULTS: In total, 317 patients were included with a mean age of 47.3 years and a mean tumor size of 39.8 mm. The most common immunophenotype was luminal (44.9%), followed by triple-negative (26.8%). Overall, 126 patients (39.7%) had an rCR, while 119 (37.5%) had pCR; the radiological and pathological responses agreed in 252 cases (79.5%). During follow-up, patients who had rCR and pCR had a better DFS curve compared to patients with non-rCR and non-pCR, while those who had rCR or pCR presented an intermediate curve (Log-rank p = 0.003). Multivariate analysis showed a higher risk of recurrence in patients with non-rCR and non-pCR (HR: 5,626; p = 0.020) and those who had a complete response on MRI or pathology only (HR: 4,369; p = 0.067), when compared to patients with rCR and pCR. CONCLUSIONS: The association of MRI and pathological responses after NAC might better stratify the risk of recurrence and prognosis in breast cancer patients. KEY POINTS: • Association of response evaluation after neoadjuvant chemotherapy by pathology and MRI allows better stratification of prognosis. • Complete response to neoadjuvant chemotherapy on pathology and MRI was related to better disease-free survival. • Complete response on MRI or pathology only had a greater risk of recurrence.

On a new piecewise regression model with cure rate: Diagnostics and application to medical data.

In this article, we discuss an extension of the classical negative binomial cure rate model with piecewise exponential distribution of the time to event for concurrent causes, which enables the modeling of monotonic and non-monotonic hazard functions (ie, the shape of the hazard function is not assumed as in traditional parametric models). This approach produces a flexible cure rate model, depending on the choice of time partition. We discuss local influence on this negative binomial power piecewise exponential model. We report on Monte Carlo simulation studies and application of the model to real melanoma and leukemia datasets.

PD-L1 expression patterns in oral cancer as an integrated approach for further prognostic classification.

BACKGROUND: Despite the well-known role of programmed cell death ligand 1 (PD-L1) in promoting immune resistance in oral squamous cell carcinoma (OSCC), its potential utility as a prognostic biomarker is undetermined. We evaluated PD-L1 expression as predictor of survival in patients with OSCC and explored PD-L1 expression patterns. METHODS: We conducted a retrospective cohort study that assessed PD-L1 expression through immunohistochemistry in 123 surgical specimens of OSCC. A first approach evaluated tumor proportion scores (TPS) and combined proportion scores (CPS). Next, expression patterns were examined by evaluating PD-L1 localization in tumor nests, as well as the interfaces of tumor cells (TC) and immune cells (IC) in the tumor microenvironment. RESULTS: High-level PD-L1 expression determined by TPS and CPS using variable cutoffs was not associated with survival. Immunohistochemistry revealed that TC expressed PD-L1 in either patchy or diffuse patterns. The patchy pattern was an independent risk factor for overall survival. Furthermore, expression patterns in the tumor immune microenvironment showed that most cases expressed PD-L1 on both TC and IC, while PD-L1 non-expressors had the lowest overall survival. CONCLUSION: PD-L1 expression patterns in the context of localization in tumor nests and TC-IC interactions represent antitumor immune responses better than either TPS or CPS. Our suggested classification system may have important implications for the characterization of OSCC and for the use of PD-L1 as a prognostic biomarker.

Weighted Lindley frailty model: estimation and application to lung cancer data.

In this paper, we propose a novel frailty model for modeling unobserved heterogeneity present in survival data. Our model is derived by using a weighted Lindley distribution as the frailty distribution. The respective frailty distribution has a simple Laplace transform function which is useful to obtain marginal survival and hazard functions. We assume hazard functions of the Weibull and Gompertz distributions as the baseline hazard functions. A classical inference procedure based on the maximum likelihood method is presented. Extensive simulation studies are further performed to verify the behavior of maximum likelihood estimators under different proportions of right-censoring and to assess the performance of the likelihood ratio test to detect unobserved heterogeneity in different sample sizes. Finally, to demonstrate the applicability of the proposed model, we use it to analyze a medical dataset from a population-based study of incident cases of lung cancer diagnosed in the state of São Paulo, Brazil.

Sentinel Node Status is the Most Important Prognostic Information for Clinical Stage IIB and IIC Melanoma Patients.

BACKGROUND: Sentinel node biopsy (SNB) for melanoma patients has been questioned. We aimed to study high-risk stage II melanoma patients who underwent SNB to determine what the prognostic factors regarding recurrence and mortality were, and evaluate how relevant SNB status is in this scenario. METHODS: This was a retrospective analysis of clinical stage IIB/IIC melanoma patients who underwent SNB from 2000 to 2015 in a single institution. Prognostic factors related to distant recurrence-free survival (DRFS) and melanoma-specific survival (MSS) were assessed from multiple Cox regression. Relevant variables were used to create risk predictor nomograms for DRFS and MSS. RESULTS: From 1213 SNB, 259 were performed for clinical stage IIB/IIC melanoma patients. SNB status was the most important variable for both endpoints. Patients with positive SNB presented median DRFS of 35.73 months (95% CI 21.38-50.08, SE 7.32) and median MSS of 66.4 months (95% CI 29.76-103.03, SE 18.69), meanwhile both median DRFS and MSS were not achieved for those with negative SNB (logrank < 0.0001). Both nomograms have been internally validated and presented adequate calibration (C-index was 0.734 for DRFS and 0.718 for MSS). CONCLUSIONS: SNB status was the most important risk factor in our cohort of clinical stage IIB and IIC patients and, in conjunction with well-established primary tumor characteristics, should not be abandoned. Their use in prognosis for these patients remains extremely useful for daily practice.

Small renal masses in Latin-American population: characteristics and prognostic factors for survival, recurrence and metastasis - a multi-institutional study from LARCG database.

BACKGROUND: To evaluate demographic, clinical and pathological characteristics of small renal masses (SRM) (≤ 4 cm) in a Latin-American population provided by LARCG (Latin-American Renal Cancer Group) and analyze predictors of survival, recurrence and metastasis. METHODS: A multi-institutional retrospective cohort study of 1523 patients submitted to surgical treatment for non-metastatic SRM from 1979 to 2016. Comparisons between radical (RN) or partial nephrectomy (PN) and young or elderly patients were performed. Kaplan-Meier curves and log-rank tests estimated 10-year overall survival. Predictors of local recurrence or metastasis were analyzed by a multivariable logistic regression model. RESULTS: PN and RN were performed in 897 (66%) and 461 (34%) patients. A proportional increase of PN cases from 48.5% (1979-2009) to 75% (after 2009) was evidenced. Stratifying by age, elderly patients (≥ 65 years) had better 10-year OS rates when submitted to PN (83.5%), than RN (54.5%), p = 0.044. This disparity was not evidenced in younger patients. On multivariable model, bilaterality, extracapsular extension and ASA (American Society of Anesthesiologists) classification ≥3 were predictors of local recurrence. We did not identify significant predictors for distant metastasis in our series. CONCLUSIONS: PN is performed in Latin-America in a similar proportion to developed areas and it has been increasing in the last years. Even in elderly individuals, if good functional status, sufficiently fit to surgery, and favorable tumor characteristics, they should be encouraged to perform PN. Intending to an earlier diagnosis of recurrence or distant metastasis, SRM cases with unfavorable characteristics should have a more rigorous follow-up routine.

Number of mesothelial cells as a measure of adequacy criteria for pleural effusions: A multi-institutional study.

BACKGROUND: The development of a terminology system is essential to allow uniformity in reporting serous fluid specimens. An important topic to cover is the issue of specimen adequacy. In the present study, we aimed to evaluate whether there is a correlation between number of mesothelial cells and overall improved sensitivity and adequacy control of tests. METHODS: Cases of negative pleural fluids with concomitant positive pleural biopsies were selected from two referral institutions, with observation of the number of mesothelial cells in 10 high-power fields, comparing the results with a control group (cases with negative biopsies, ie, true negatives). Comparisons were conducted using the nonparametric Mann-Whitney U test. Data were analysed for sensitivity and specificity derived from the receiver operating characteristics curve. For the choice of an optimal cut-off of mesothelial cells, receiver operating curve analysis was constructed and the Youden index was calculated. RESULTS: A total of 112 pleural effusions with paired pleural biopsies were studied. There was no difference in distributions of the number of mesothelial cells between cases with a positive biopsy (false negatives) and the control group (median = 39 vs median = 30, respectively, P-value = .974). However, simple logistic regression found a cut-off of 750 cells per 10 high-power fields as an optimal number for improved sensitivity (72.7%), with fair discriminatory power. CONCLUSIONS: Enumeration of mesothelial cells may improve the sensitivity of the cytological diagnosis of malignant pleural effusion, serving as an internal quality control for the test's overall accuracy.

Should we wait 3 months for a repeat aspiration in non-diagnostic/indeterminate thyroid nodules? A cancer centre experience.

INTRODUCTION: The Bethesda System recommends repeat fine needle aspiration (rFNA) as a management option for nodules classified under the non-diagnostic (ND) and atypia of undetermined significance (AUS/FLUS) categories. We evaluated the impact of an rFNA in diagnostic resolution and the role of early (≤3 months) vs delayed (more than 3 months) rFNA of nodules initially diagnosed as ND and AUS/FLUS. METHODS: We retrospectively collected all thyroid FNA performed in a 4-year period with repeat aspiration. For cases initially signed out as ND or AUS/FLUS, diagnostic resolution was defined as a change to a Bethesda System category other than these two on rFNA. Comparison and regression models were fitted to identify the impact of time of rFNA on diagnostic resolution. RESULTS: In total, 184 cases were initially assigned as ND and 143 as AUS/FLUS, with overall diagnostic resolution rates for the reassessment of these nodules calculated at 70.1% and 62.9%, respectively. For ND cases, time of rFNA was not significantly associated with diagnostic resolution (P > .05). For AUS/FLUS nodules, however, repeat aspiration performed in more than 3 months after the initial diagnosis was 2.5 times more likely to achieve a resolution in diagnosis than early rFNA (P = .024). CONCLUSIONS: Repeat aspiration of ND and AUS/FLUS nodules helped define diagnosis for the majority of cases, being highly effective in determining correct patient management. For AUS/FLUS nodules, repeat aspiration performed more than 3 months after the initial diagnosis was associated with a higher diagnostic resolution.

The Potential Clinical Implications of Circulating Tumor Cells and Circulating Tumor Microemboli in Gastric Cancer.

BACKGROUND: Gastric adenocarcinoma (GAC) is the third deadliest malignant neoplasm worldwide, mostly because of late disease diagnosis, low chemotherapy response rates, and an overall lack of tumor biology understanding. Therefore, tools for prognosis and prediction of treatment response are needed. Quantification of circulating tumor cells (CTCs) and circulating tumor microemboli (CTM) and their expression of biomarkers has potential clinical relevance. Our aim was to evaluate CTCs and CTM and their expression of HER2 and plakoglobin in patients with nonmetastatic GAC, correlating the findings to clinicopathological data. MATERIALS AND METHODS: CTC enrichment was performed with isolation by size of epithelial tumor cells, and the analysis was performed with immunocytochemistry and microscopy. Two collections were made: one at diagnosis (55 samples before neoadjuvant treatment) and one after surgery and before adjuvant therapy (33 samples). RESULTS: A high detection rate of CTCs (90%) was observed at baseline. We evaluated HER2 expression in 45/55 biopsy samples and in 42/55 CTC samples, with an overlap of 36 subjects. Besides the good agreement observed for HER2 expression in primary tumors and paired CTCs for 36 cases (69.4%; κ = 0.272), the analysis of HER2 in CTCs showed higher positivity (43%) compared with primary tumors (11%); 3/5 patients with disease progression had HER2-negative primary tumors but HER2-positive CTCs. A significant CTC count drop in follow-up was seen for CTC-HER2-positive cases (4.45 to 1.0 CTCs per mL) compared with CTC-HER2-negative cases (2.6 to 1.0 CTCs per mL). The same was observed for CTC-plakoglobin-positive cases (2.9 to 1.25 CTCs per mL). CONCLUSION: CTC analysis, including their levels, plakoglobin, and HER2 expression, appears to be a promising tool in the understanding the biology and prognosis of GAC. IMPLICATIONS FOR PRACTICE: The analysis of circulating tumor cell levels from the blood of patients with gastric adenocarcinoma, before and after neoadjuvant treatment, is useful to better understand the behavior of the disease as well as the patients more likely to respond to treatment.