External validation of nomogram to predict inguinal lymph node metastasis in patients with penile cancer and clinically negative lymph nodes.

INTRODUCTION: Penile cancer (PC) occurs less frequently in Europe and in the United States than in South America and parts of Africa. Lymph node (LN) involvement is the most important prognostic factor, and inguinal LN (ILN) dissection can be curative; however, ILN dissection has high morbidity. A nomogram was previously developed based on clinicopathological features of PC to predict ILN metastases. Our objective was to conduct an external validation of the previously developed nomogram based on our population. MATERIALS AND METHODS: We included men with cN0 ILNs who underwent ILN dissection for penile carcinoma between 2000 and 2014. We performed external validation of the nomogram considering three different external validation methods: k-fold, leave-oneout, and bootstrap. We also analyzed prognostic variables. Performance was quantified in terms of calibration and discrimination (receiver operator characteristic curve). A logistic regression model for positive ILNs was developed based on clinicopathological features of PC. RESULTS: We analyzed 65 men who underwent ILN dissection (cN0). The mean age was 56.8 years. Of 65 men, 24 (36.9%) presented with positive LNs. A median 21 ILNs were removed. Considering the three different methods used, we concluded that the previously developed nomogram was not suitable for our sample. CONCLUSIONS: In our study, the previously developed nomogram that was applied to our population had low accuracy and low precision for correctly identifying patients with PC who have positive ILNs.

Time between diagnosis and surgical treatment on pathological and clinical outcomes in prostate cancer: does it matter?

INTRODUCTION: Prostate cancer (PC) most of the time presents with an indolent course. Thus, delays in treatment due to any causes might not affect long-term survival and may not affect cancer cure rates. PURPOSE: In this study, we evaluated the effect of delay-time between PC diagnosis and radical prostatectomy regarding oncological outcomes: Gleason score upgrade on surgical specimen, pathologic extracapsular extension (ECE) on surgical specimen, and postoperative biochemical recurrence (BCR) on follow-up. METHODS: We evaluated PC patients who underwent radical prostatectomy (RP) regarding clinical and pathological findings and theirs respective interval between diagnosis and surgical treatment measured in days and months. We used univariate and multivariate logistic regression to evaluate the impact of interval-time. RESULTS: A total of 908 PC patients underwent RP between 2006 and 2014. Mean age was 61.5 years, the mean time-to-surgery was 191 days (> 6 months) and 187 (20.5%) patients had BCR, with a mean follow-up of 44 months. According to our analysis, no statistically significant maximum cut-off time interval between diagnostic biopsy and surgery could be established (p = 0.215). Regardless of interval-time: ≤ 6 months (56.5%), 6-12 months (38.5%), and > 12 months (5.1%) after biopsy, we found no time interval correlated with poor oncological outcomes. This study has several limitations. It was retrospective and had a mean follow-up of 4 years. Additional follow-up is necessary to determine whether these findings will be maintained over time. CONCLUSIONS: We showed that the time between diagnosis and surgical treatment did not affect the oncological outcomes in our study.

Detection of ALK fusion transcripts in FFPE lung cancer samples by NanoString technology.

BACKGROUND: ALK-rearranged lung cancers exhibit specific pathologic and clinical features and are responsive to anti-ALK therapies. Therefore, the detection of ALK-rearrangement is fundamental for personalized lung cancer therapy. Recently, new molecular techniques, such as NanoString nCounter, have been developed to detect ALK fusions with more accuracy and sensitivity. METHODS: In the present study, we intended to validate a NanoString nCounter ALK-fusion panel in routine biopsies of FFPE lung cancer patients. A total of 43 samples were analyzed, 13 ALK-positive and 30 ALK-negative, as previously detected by FISH and/or immunohistochemistry. RESULTS: The NanoString panel detected the presence of the EML4-ALK, KIF5B-ALK and TFG-ALK fusion variants. We observed that all the 13 ALK-positive cases exhibited genetic aberrations by the NanoString methodology. Namely, six cases (46.15%) presented EML-ALK variant 1, two (15.38%) presented EML-ALK variant 2, two (15.38%) presented EML-ALK variant 3a, and three (23.07%) exhibited no variant but presented unbalanced expression between 5'/3' exons, similar to other positive samples. Importantly, for all these analyses, the initial input of RNA was 100 ng, and some cases displayed poor RNA quality measurements. CONCLUSIONS: In this study, we reported the great utility of NanoString technology in the assessment of ALK fusions in routine lung biopsies of FFPE specimens.

Accuracy of microRNAs as markers for the detection of neck lymph node metastases in patients with head and neck squamous cell carcinoma.

BACKGROUND: The presence of metastatic disease in cervical lymph nodes of head and neck squamous cell carcinoma (HNSCC) patients is a very important determinant in therapy choice and prognosis, with great impact in overall survival. Frequently, routine lymph node staging cannot detect occult metastases and the post-surgical histologic evaluation of resected lymph nodes is not sensitive in detecting small metastatic deposits. Molecular markers based on tissue-specific microRNA expression are alternative accurate diagnostic markers. Herein, we evaluated the feasibility of using the expression of microRNAs to detect metastatic cells in formalin-fixed paraffin-embedded (FFPE) lymph nodes and in fine-needle aspiration (FNA) biopsies of HNSCC patients. METHODS: An initial screening compared the expression of 667 microRNAs in a discovery set comprised by metastatic and non-metastatic lymph nodes from HNSCC patients. The most differentially expressed microRNAs were validated by qRT-PCR in two independent cohorts: i) 48 FFPE lymph node samples, and ii) 113 FNA lymph node biopsies. The accuracy of the markers in identifying metastatic samples was assessed through the analysis of sensitivity, specificity, accuracy, negative predictive value, positive predictive value, and area under the curve values. RESULTS: Seven microRNAs highly expressed in metastatic lymph nodes from the discovery set were validated in FFPE lymph node samples. MiR-203 and miR-205 identified all metastatic samples, regardless of the size of the metastatic deposit. Additionally, these markers also showed high accuracy when FNA samples were examined. CONCLUSIONS: The high accuracy of miR-203 and miR-205 warrant these microRNAs as diagnostic markers of neck metastases in HNSCC. These can be evaluated in entire lymph nodes and in FNA biopsies collected at different time-points such as pre-treatment samples, intraoperative sentinel node biopsy, and during patient follow-up. These markers can be useful in a clinical setting in the management of HNSCC patients from initial disease staging and therapy planning to patient surveillance.

Solitary fibrous tumours involving the genitourinary tract: a case series in rare locations, highlighting the role of STAT6 immunohistochemistry.

Solitary fibrous tumour (SFT) is a mesenchymal neoplasm with variable behaviour, very rarely involving the genitourinary (GU) tract. Most reported cases correspond to isolated case reports. STAT6 immunohistochemistry is a more recent and reliable diagnostic marker. The pathology database of two tertiary institutes was searched for SFTs involving the GU tract. STAT6 strong diffuse nuclear staining confirmed the diagnosis in all four cases, and the NAB2::STAT6 fusion was demonstrated by NGS in one case. Two cases were diagnosed in needle biopsy, one involving the prostate and the other involving the seminal vesicle. One case corresponded to a pelvic mass inseparable from and infiltrating the prostate and bladder. The remainder represented an exceedingly rare involvement of the spermatic cord. Involvement by a SFT should be considered in the differential diagnosis of spindle cell lesions involving GU organs. STAT6 strong diffuse nuclear staining is an important ancillary tool, particularly in a biopsy.

Analysis of RPL37A, MTSS1, and HTRA1 expression as potential markers for pathologic complete response and survival.

BACKGROUND: Non-metastatic locally advanced breast carcinoma (LABC) treatment involves neoadjuvant chemotherapy (NCT). We evaluated the association of clinical-pathological data and immunoexpression of hormone receptors, HER2 and Ki67, and new biomarkers, RPL37A, MTSS1 and HTRA1, with pathological complete response (PCR) or tumour resistance (stable disease or disease progression), disease-free survival (DFS) and cancer-specific survival (CSS). METHODS: This is a retrospective study of 333 patients with LABC who underwent NCT. Expression of MTSS1, RPL37A and HTRA1/PRSS11 was evaluated by immunohistochemistry in TMA slides. Cutoff values were established for low and high tumour expression. ROC plotter evaluated response to NCT. Chi-square test for factors related to PCR, and Kaplan-Meier test and Cox model for factors related to DFS and CSS were prformed. RESULTS: The mean follow-up was 70.0 months and PCR rate was 15.6%. At 120 months, DFS rate was 32.5% and CSS rate was 67.1%. In multivariate analysis, there was an association between: (1) necrosis presence, intense inflammatory infiltrate, ER absence, HER2 molecular subtype and high RPL3A expression with increased odds of PCR; (2) lymph node involvement (LNI), high Ki67, low RPL37A and high HTRA1 expression with increased risk for NCT non-response; (3) LNI, high proliferation, necrosis absence, low RPL37A and high HTRA1 expression with increased recurrence risk; (4) advanced LNI, ER negative tumours, high HTRA1, low RPL37A expression and desmoplasia presence with higher risk of cancer death. CONCLUSION: RPL37A is a potential biomarker for response to NCT and for prognosis. Additional studies evaluating HTRA1 and MTSS1 prognostic value are needed.

The role of oncoplastic breast conserving treatment for locally advanced breast tumors. A matching case-control study.

BACKGROUND: Breast conserving surgery (BCS) after neoadjuvant chemotherapy (NC) in patients with locally advanced breast cancer (LABC) is an infrequent procedure. In these patients the association with BCS and oncoplastic surgery (OS) is reported as a possible procedure in case-series, but there are limited case-control studies. METHODS: A matched case-control study evaluated LABC submitted to NC and BCS. We evaluated 78 patients submitted to doxorubicin-cyclophosphamide regimen followed by paclitaxel regimen. The match case-control proportion was 2:1 and the patients were selected by tumor size, clinical T stage and year of diagnosis. RESULTS: 52 underwent classic BCS and 26 OS. The average size tumor was 5.25 cm and 88.5% of the tumors were larger than 3 cm. The clinical and pathological group characteristics were similar, except the weight of surgical specimens (p = 0.004), and surgical margins (p = 0.06), which were higher in OS group. The rate of complete pathologic response was 26.9%. 97.4% received postoperative radiotherapy. At 67.1 months of follow up, 10.2% had local recurrence (LR) and 12.8% locoregional recurrence (LRR) and 19.2% died because disease progression. The overall survival at 60 months was 81.7%. After surgery the disease free-survival at 60 months was 76.5%. The was no difference between groups related to pathologic response (p = 0.42), LR (p = 0.71), LRR (p = 1.00), overall survival (p = 0.99) and disease specific survival (p = 0.87). CONCLUSION: This study corroborates the fact that OS is a safety procedure for LABC, offering the similar oncologic results observed in patients submitted to classic BCS.

External validation of nomogram to predict inguinal lymph node metastasis in patients with penile cancer and clinically negative lymph nodes

ABSTRACT Introduction Penile cancer (PC) occurs less frequently in Europe and in the United States than in South America and parts of Africa. Lymph node (LN) involvement is the most important prognostic factor, and inguinal LN (ILN) dissection can be curative; however, ILN dissection has high morbidity. A nomogram was previously developed based on clinicopathological features of PC to predict ILN metastases. Our objective was to conduct an external validation of the previously developed nomogram based on our population. Materials and methods We included men with cN0 ILNs who underwent ILN dissection for penile carcinoma between 2000 and 2014. We performed external validation of the nomogram considering three different external validation methods: k-fold, leave-one-out, and bootstrap. We also analyzed prognostic variables. Performance was quantified in terms of calibration and discrimination (receiver operator characteristic curve). A logistic regression model for positive ILNs was developed based on clinicopathological features of PC. Results We analyzed 65 men who underwent ILN dissection (cN0). The mean age was 56.8 years. Of 65 men, 24 (36.9%) presented with positive LNs. A median 21 ILNs were removed. Considering the three different methods used, we concluded that the previously developed nomogram was not suitable for our sample. Conclusions In our study, the previously developed nomogram that was applied to our population had low accuracy and low precision for correctly identifying patients with PC who have positive ILNs.

Tuberculose pulmonar / Pulmonary tuberculosis

A tuberculose (TB) é uma doença infecto-contagioda, prevenível e curável, constituindo ainda hoje uma ameaça para a saúde pública no Brasil. A TB nunca deixou de ser um problema do terceiro mundo, em geral. Segundo a Organização Mundial da Saúde (OMS), o Brasil ocupa hoje o 14º lugar entre os 23 países responsáveis por 80 por cento do total de casos de tuberculose. No Brasil, desde a década de 1980, vêm sendo notificados em torno de 80 mil a 90 mil casos anuais, mais ou menos estáveis, com uma mortalidade aproximadamente de 6 mil casos por ano. Apresenta-se sob a forma pulmonar ou extrapulmonar. Deve-se fazer o diagnóstico de forma rápida, tendo em vista iniciar logo o tratamento, reduzindo o tempo de transmissão da doença e conseqüentemente o número de infectados.

Tuberculosis (TB) is an infectious and contagious illness, healing and preventive that still constitute nowadays a treat for the public health in Brazil. TB has always been a third world problem. In accordance with OMS, Brazil rank today the 14th place, among 23 countries responsible for 80 per cent of the cases of TB. In Brazil, since the 80's, around 80 to 90 thousand cases yearly are notified, with mortality nearby 6 thousand cases per annum. Present itself in a pulmonary or extrapulmonary way. The diagnosis must be early, to treat it fast, to reduce the time of transmission and the number of sick patients.

Tratamento da insuficiência cardíaca descompensada / Decompensated heart failure treatment

A insuficiência (IC) descompensada é causa freqüente de internações hospitalares em todo o mundo. Constitui o principal motivo de internações de pacientes com mais de 65 anos de idade, apresentando elevada taxa de mortalidade. A IC pode ser classificada como leve, moderada ou severa (NYHA), mas freqüentemente seus sintomas e sua evolução são insidiosos, em geral decorrentes de lesões no músculo cardíaco. Diagnóstico e trataemtno precoces são essenciais para diminuir a evolução da doença.