Quality of life in a randomized trial comparing two neoadjuvant regimens for locally advanced rectal cancer-INCAGI004.

BACKGROUND: Neoadjuvant chemoradiotherapy (neoCRT) followed by surgery is the standard of care for locally advanced rectal cancer (LARC), but the emergence of different drug regimens may result in different response rates. Good clinical response translates into greater sphincter preservation, but quality of life (QOL) may be impaired after treatment due to chemoradiotherapy and surgical side effects. OBJECTIVE: To prospectively evaluate the impact of clinical response and surgical resection on QOL in a randomized trial comparing two different neoCRT regimens. METHODS: Stage II and III rectal cancer patients were randomized to receive neoCRT with either capecitabine (group 1) or 5-Fu and leucovorin (group 2) concomitant to long-course radiotherapy. Clinical downstaging was accessed using MRI 6-8 weeks after treatment. EORTCs QLQ-C30 and CR38 were applied before treatment (T0), after neoCRT (T1), after rectal resection (T2), early after adjuvant chemotherapy (T3), and 1 year after the end of treatment or stoma closure (T4). The Wexner scale was used for fecal incontinence evaluation at T4. A C30SummaryScore (Geisinger and cols.) was calculated to compare QOL results. RESULTS: Thirty-two patients were assigned to group 1 and 31 to group 2. Clinical downstaging occurred in 70.0% of group 1 and 53.3% of group 2 (p = 0.288), and sphincter preservation was 83.3% in group 1 and 80.0% in group 2 (p = 0.111). No significant difference in QOL was detected when comparing the two treatment groups after neoCRT using QLQ-C30. However, the CR38 module detected differences in micturition problems (15.3 points), gastrointestinal problems (15.3 points), defecation problems (11.8 points), and sexual satisfaction (13.3 points) favoring the capecitabine group. C30SummaryScore detected significant improvement comparing T0 to T1 and deterioration comparing T1 to T2 (p = 0.025). The mean Wexner scale score was 9.2, and a high score correlated with symptoms of diarrhea and defecation problems at T4. CONCLUSIONS: QOL was equivalent between groups after neoCRT except for micturition problems, gastrointestinal problems, defecation problems, and sexual satisfaction favoring the capecitabine arm after. The overall QOL using the C30SummaryScore was improved after neoCRT, but decreased following rectal resection, returning to basal levels at late evaluation. Fecal incontinence was high after sphincter preservation. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03428529.

Salvage abdominoperineal resection for anal cancer following chemoradiation: a proposed scoring system for predicting postoperative survival.

BACKGROUND AND OBJECTIVES: Anal carcinoma is treated primarily by chemoradiation. Failure of this treatment requires salvage surgery. The aims of this retrospective study were to assess the survival probability after rescue surgery and design a pathological risk score (PRS) to predict postoperative outcome. METHODS: From 1982 to 2011, the clinical and pathological data of 111 patients treated with chemoradiation or radiation alone and abdominoperineal resection were reviewed. The Kaplan-Meier method was used to assess overall survival and parametric modeling was applied to determine prognostic factors and design a PRS. RESULTS: The 2- and 5-year overall survival rates were 60% and 24.5%, respectively. The multivariate analysis showed that nodal disease (P < 0.03), resection margin (P < 0.001), and perineural and/or lymphovascular invasion (P < 0.0001) were significantly associated with survival. Patients who presented negative values for these three variables were estimated to show a 5-year survival rate of 55% compared with 0.03% for patients who presented positive values. CONCLUSIONS: Positive surgical margin, the presence of perineural and/or lymphovascular invasion and positive nodal involvement were identified as significant independent predictors of mortality. The PRS was shown to be highly predictive of postoperative outcome.

GLIPR1 and SPARC expression profile reveals a signature associated with prostate Cancer Brain metastasis.

Despite advances in treatment of lethal prostate cancer, the incidence of prostate cancer brain metastases is increasing. In this sense, we analyzed the molecular profile, as well as the functional consequences involved in the reciprocal interactions between prostate tumor cells and human astrocytes. We observed that the DU145 cells, but not the LNCaP cells or the RWPE-1 cells, exhibited more pronounced, malignant and invasive phenotypes along their interactions with astrocytes. Moreover, global gene expression analysis revealed several genes that were differently expressed in our co-culture models with the overexpression of GLIPR1 and SPARC potentially representing a molecular signature associated with the invasion of central nervous system by prostate malignant cells. Further, these results were corroborated by immunohistochemistry and in silico analysis. Thus, we conjecture that the data here presented may increase the knowledge about the molecular mechanisms associated with the invasion of CNS by prostate malignant cells.

Transcriptome Analysis Identifies ALCAM Overexpression as a Prognosis Biomarker in Laryngeal Squamous Cell Carcinoma.

BACKGROUND: Laryngeal squamous cell carcinoma (LSCC) is one of the most incident tumors in the world, especially in developing countries, such as Brazil. Different from other tumors, LSCC prognosis did not improve during the past four decades. Therefore, the objective of this study was to develop biomarkers that can predict LSCC patient's prognosis. RESULTS: Transcriptome analysis pointed out 287 overexpressed genes in LSCC in comparison to adjacent mucosa. Among these, a gene-pattern signature was created with 24 genes associated with prognosis. The Bayesian clustering of both Brazil and The Cancer Genome Atlas (TCGA) data pointed out clusters of samples possessing significative differences in the prognosis, and the expression panel of three genes (ALCAM, GBP6, and ME1) was capable to distinguish patients with worse prognosis with an accuracy of 97%. Survival analyses with TCGA data highlighted ALCAM gene expression as an independent prognostic factor for LSCC. This was further confirmed through immunohistochemistry, using a validation set of Brazilian patients. ALCAM expression was not associated with prognosis for other head and neck tumor sites. CONCLUSION: ALCAM overexpression seems to be an independent prognosis biomarker for LSCC patients.

HMGA2 overexpression plays a critical role in the progression of esophageal squamous carcinoma.

Esophageal Squamous Cell Carcinoma (ESCC) is the most common esophageal tumor worldwide. However, there is still a lack of deeper knowledge about biological alterations involved in ESCC development. High Mobility Group A (HMGA) protein family has been related with poor outcome and malignant cell transformation in several tumor types. In this way, the aim of this study was to analyze the expression of HMGA1 and HMGA2 expression in ESCC and their role in crucial cellular features. We evaluated HMGA1 and HMGA2 mRNA expression in 52 paired ESCC and normal surrounding tissue samples by qRT-PCR. Here, we show that HMGA2, but not HMGA1, is overexpressed in ESCC samples. This result was further confirmed by the immunohistochemical analysis. Indeed, accordingly to mRNA expression data, HMGA2, but not HMGA1, was overexpressed in approximately 90% of ESCC samples, while it was barely expressed in the respective control. Conversely, HMGA1, but not HMGA2, was overexpressed in esophageal adenocarcinoma samples. Interestingly, HMGA2 abrogation attenuated the malignant phenotype of two ESCC cell lines, suggesting that HMGA2 overexpression is involved in ESCC progression.

Prognostic significance of p53 protein expression in early gastric cancer.

Mutations of the p53 tumor suppressor gene have been associated with abnormalities in cell cycle regulation, DNA repair and synthesis, apoptosis, and it has been implicated in the prognosis of advanced gastric cancer. The aim of this study was to evaluate the occurrence of p53 gene mutation and its possible prognostic implications in early gastric cancer. In a retrospective study, we studied 80 patients with early gastric cancer treated surgically between 1982 and 2001. Mutation of p53 gene was investigated in surgical gastric specimens by immunohistochemistry, and results were analyzed in relation to gender, age, macroscopic appearance, size and location of tumor, presence of lymph nodes, Lauren's histological type, degree of differentiation, and the 5-year survival. The expression of p53 was more frequent among the intestinal type (p = 0.003), the differentiated (p = 0.007), and the macroscopically elevated tumors (p = 0.038). Nevertheless, the isolated expression of p53 was not associated with the 5-year survival, or with the frequency of lymph node involvement. The degree of differentiation was detected as an independent factor related to the outcome of patients (0.044). Significantly shorter survival time was found in p53-negative compared with p53-positive patients, when considering the degree of differentiation of tumors, as assessed by Cox regression analysis (0.049). The association of p53 with the intestinal type, the degree of differentiation and morphological characteristics, may reflect the involvement of chronic inflammatory process underlying early gastric cancer. In this population sample, the expression of p53 alone has no prognostic value for early gastric cancer. However, the significant difference in p53 expression between subgroups of degree of differentiation of tumors can influence post-operative outcome of patients and may be related to possible distinct etiopathogenic subtypes.

Hemangioendotelioma epitelióide hepático: relato de caso com tratamento multimodal / Epithelioid hemangioendothelioma of the liver: report of a case with multimodal treatment

Os autores apresentam um caso raro de hemangioendotelioma epitelióide hepático multicêntrico de uma paciente oligossintomática, tratada inicialmente com ressecção e alcoolização. Na sua recidiva, foi submetida à radioablação. Revisando a literatura, os autores concluem que a ressecção permanece como o principal tratamento, associada ou não a métodos ablativos, e que o transplante tem indicação na doença multinodular bilateral.

GIST gástrico: experiência do INCA / Gastric stromal tumors: the experience of the Brazilian National Cancer Institute

Introdução: Tumor estromal gastrointestinal (GIST) é uma doença relativamente rara e a cirurgia se constitui no tratamento principal deste tumor. Existem apenas poucos centros com experiência no tratamento desta neoplasia.O objetivo do trabalho é analisar os resultados do tratamento cirúrgico dos pacientes portadores de GIST gástrico operados em uma mesma instituição. Métodos: Estudo retrospectivo baseado na análise de 20 pacientes com diagnóstico confirmado de GIST gástrico operados no Instituto Nacional de Câncer (INCA- Rio de Janeiro) entre 1986 e 2000. Todos os dados foramrevisados, enfocando-se as características histopatológicas (localização, número de mitoses e tamanho do tumor), as características dos pacientes (idade, sexo e apresentação clínica) e os resultados cirúrgicos (tipos de cirurgia, morbidade, mortalidade e sobrevida de acordo com a classificação proposta por Shiu). Resultados: Onze pacientes eram do sexo masculino e 9 do sexo feminino. A mediana de idade foi de 57 anos. O tamanho médio do tumor foi de 14,7 cm. Setenta por cento dos pacientes tinham tumor de alto grau e 65 por cento dos tumores se localizavam na porção proximal do estômago. Gastrectomia subtotal foi realizada em 50 por cento dos casos, gastrectomia total em 35 por cento e gastrectomia atípica em 10 por cento. Ressecção gástrica isolada foi realizada em seis casos (grupo 1), ressecção de dois órgãos foi feita em cinco casos (grupo 2) e ressecção de mais de dois órgãos em oito casos (grupo 3). A morbidade operatória global foi de 35 por cento. O grupo 1 não teve morbidade, o grupo 2 teve morbidade de 20 por cento e o grupo 3, de 70 por cento. A mortalidade operatória foi de 10 por cento (2 pacientes). Dez por cento dos pacientes foram classificados como estádio 0, 25 por cento como estádio I e 65 por cento, estádio II de acordo com a classificação de Shiu. A sobrevida em 5 anos para o estádio 0 foi de 100 por cento enquanto que o estádio II apresentou sobrevida nula em 5 anos...