INTERVENTIONS FOR THE TREATMENT OF IRRITABLE BOWEL SYNDROME: A REVIEW OF COCHRANE SYSTEMATIC REVIEWS.

BACKGROUND: Irritable bowel syndrome (IBS) is a complex gastrointestinal disorder, whose understanding is relatively uncertain, and the treatment guidance decision still represents a challenge. OBJECTIVE: To identify and critically appraise systematic reviews (SRs) published in the Cochrane Database of SRs (CDSR) on the effects of interventions (pharmacological and non-pharmacological) for the treatment of IBS. METHODS: The search was conducted at the Cochrane Library in May 2020. The methodological quality of the SRs was evaluated by the AMSTAR-2 tool. RESULTS: Eight SRs with moderate to high quality were included, which addressed the treatments: (a) pharmacological: volume agents, antispasmodics, antidepressants and tegaserod; and (b) non-pharmacological: homeopathy, acupuncture, phytotherapy, biofeedback, psychological interventions and hypnotherapy. The results were favorable to antispasmodic drugs and antidepressants regarding the improvement of clinical symptoms. There was no difference between volume agents or tegaserod when compared to placebo. Acupuncture and homeopathy showed a little improvement in symptoms compared to placebo, but the certainty of this evidence was considered low to very low. Psychological interventions seem to improve the overall assessment of the patient and relief symptoms such as abdominal pain. However, there was no long-term follow-up of these patients. The results of the other treatments were considered uncertain due to the high risk of bias. CONCLUSION: Considering the low quality of the studies included in the SRs, pharmacological treatment with antispasmodics and antidepressants seems to be beneficial for patients with IBS. Among non-pharmacological interventions, psychological interventions seem to be beneficial. However, further clinical trials are recommended with greater methodological rigor to prove these findings.

Intervenções para o tratamento da síndrome do intestino irritável: revisão de revisões sistemáticas Cochrane / Interventions for the treatment of irritable bowel syndrome: a review of cochrane systematic reviews

ABSTRACT BACKGROUND: Irritable bowel syndrome (IBS) is a complex gastrointestinal disorder, whose understanding is relatively uncertain, and the treatment guidance decision still represents a challenge. OBJECTIVE: To identify and critically appraise systematic reviews (SRs) published in the Cochrane Database of SRs (CDSR) on the effects of interventions (pharmacological and non-pharmacological) for the treatment of IBS. METHODS: The search was conducted at the Cochrane Library in May 2020. The methodological quality of the SRs was evaluated by the AMSTAR-2 tool. RESULTS: Eight SRs with moderate to high quality were included, which addressed the treatments: (a) pharmacological: volume agents, antispasmodics, antidepressants and tegaserod; and (b) non-pharmacological: homeopathy, acupuncture, phytotherapy, biofeedback, psychological interventions and hypnotherapy. The results were favorable to antispasmodic drugs and antidepressants regarding the improvement of clinical symptoms. There was no difference between volume agents or tegaserod when compared to placebo. Acupuncture and homeopathy showed a little improvement in symptoms compared to placebo, but the certainty of this evidence was considered low to very low. Psychological interventions seem to improve the overall assessment of the patient and relief symptoms such as abdominal pain. However, there was no long-term follow-up of these patients. The results of the other treatments were considered uncertain due to the high risk of bias. CONCLUSION: Considering the low quality of the studies included in the SRs, pharmacological treatment with antispasmodics and antidepressants seems to be beneficial for patients with IBS. Among non-pharmacological interventions, psychological interventions seem to be beneficial. However, further clinical trials are recommended with greater methodological rigor to prove these findings.

RESUMO CONTEXTO: A síndrome do intestino irritável (SII) é um distúrbio gastrointestinal complexo, cujo entendimento é relativamente incerto e a decisão de orientação do tratamento ainda representa um desafio. OBJETIVO: Identificar e avaliar criticamente as revisões sistemáticas (RSs) publicadas na base de dados de RSs Cochrane (CDSR) sobre os efeitos das intervenções (farmacológicas e não farmacológicas) para o tratamento da SII. MÉTODOS: A busca foi realizada na Biblioteca Cochrane em maio de 2020. A qualidade metodológica das RSs foi avaliada pela ferramenta AMSTAR-2. RESULTADOS: Foram incluídas oito RSs com qualidade moderada a alta, as quais abordaram os tratamentos: (a) farmacológico - agentes de volume, antiespasmódicos, antidepressivos e o tegaserod; e (b) não farmacológico - homeopatia, acupuntura, fitoterapia, biofeedback, intervenções psicológicas e hipnoterapia. Os resultados foram favoráveis aos medicamentos antiespasmódicos e antidepressivos em relação à melhora dos sintomas clínicos. Não houve diferença entre os agentes de volume ou tegaserod quando comparados ao placebo. Acupuntura e homeopatia apresentaram pequena melhora dos sintomas em comparação ao placebo, porém a qualidade da evidência foi considerada baixa a muito baixa. As intervenções psicológicas parecem melhorar a avaliação global do paciente e alívio de sintomas como dor abdominal. Contudo, não houve acompanhamento desses pacientes a longo prazo. Os resultados dos demais tratamentos foram considerados incertos devido ao alto risco de viés. CONCLUSÃO: Considerando a baixa qualidade dos estudos incluídos nas RSs, o tratamento farmacológico com antiespasmódicos e antidepressivos parece ser benéfico para os pacientes com SII. Entre os não-farmacológicos, as intervenções psicológicas parecem obter benefícios. Entretanto, novos ensaios clínicos são recomendados com maior rigor metodológico para comprovar estes achados.

Metalloproteinases and colorectal cancer. Correlation of gene expression and clinical-pathological parameters.

PURPOSE: To analyze gene and protein expression of metalloproteinases 1, 2, 9, 11 and 16 and their correlation with clinicopathological variables in colorectal adenocarcinoma. METHODS: A retrospective study of 114 patients with colorectal adenocarcinoma treated surgically in the period 2006 to 2008 in Hospital de Câncer de Barretos - Fundação Pio XII. The evaluation of gene expression was performed by RT-PCR, and protein by immunohistochemistry. The analysis of gene expression was classified as overexpressed genes and poorly expressed (fold change of approximately 2, p<0.05). The positivity of the markers in the immunohistochemical study was performed by semi-quantitative analysis. The tissue of TMA (Tissue Microarray) was done by two independent pathologists. RESULTS: The gene expression validated by immuno - histochemical was MMP-1(p= 0.00 and 1.57 fold change) and MMP - 2 (p= 0.01 and - 1.84 to fold change) when correlated with the histological types mucinous and adenocarcinoma NOS, MMP9 (p=0.01 and fold change of 1.13) and MMP-16 (p=0.03 and 1.61 fold change) when compared with the histological types villous and adenocarcinoma NOS, MMP - 11 statistically significant in relation to male (p = 0.04 and 1.65 fold change). CONCLUSIONS: The MMPs 1, 2, 9, 11 and 16 gene and protein expression with statistical significance in at least one of the clinicopathological variables studied. Thus, we conclude that these MMPs have potential as a prognostic factor in colorectal adenocarcinoma.

Metalloproteinases and colorectal cancer. Correlation of gene expression and clinical-pathological parameters

Abstract Purpose: To analyze gene and protein expression of metalloproteinases 1, 2, 9, 11 and 16 and their correlation with clinicopathological variables in colorectal adenocarcinoma. Methods: A retrospective study of 114 patients with colorectal adenocarcinoma treated surgically in the period 2006 to 2008 in Hospital de Câncer de Barretos - Fundação Pio XII. The evaluation of gene expression was performed by RT-PCR, and protein by immunohistochemistry. The analysis of gene expression was classified as overexpressed genes and poorly expressed (fold change of approximately 2, p<0.05). The positivity of the markers in the immunohistochemical study was performed by semi-quantitative analysis. The tissue of TMA (Tissue Microarray) was done by two independent pathologists. Results: The gene expression validated by immuno - histochemical was MMP-1(p= 0.00 and 1.57 fold change) and MMP - 2 (p= 0.01 and - 1.84 to fold change) when correlated with the histological types mucinous and adenocarcinoma NOS, MMP9 (p=0.01 and fold change of 1.13) and MMP-16 (p=0.03 and 1.61 fold change) when compared with the histological types villous and adenocarcinoma NOS, MMP - 11 statistically significant in relation to male (p = 0.04 and 1.65 fold change). Conclusions: The MMPs 1, 2, 9, 11 and 16 gene and protein expression with statistical significance in at least one of the clinicopathological variables studied. Thus, we conclude that these MMPs have potential as a prognostic factor in colorectal adenocarcinoma.

Immunoexpression of TS, p53, COX2, EGFR, MSH6 and MLH1 biomarkers and its correlation with degree of differentiation, tumor staging and prognostic factors in colorectal adenocarcinoma: a retrospective longitudinal study.

BACKGROUND: There are cases of colorectal tumors that, although small, show more aggressive evolution than large tumors. This motivated us to study whether there are any proteins capable of alerting about these changes. The aim here was to correlate the immunoexpression of the TS, p53, COX2, EGFR, MSH6 and MLH1 biomarkers in tumors in patients with colorectal adenocarcinoma, with the degree of cell differentiation, tumor staging and clinical-pathological prognostic factors. DESIGN AND SETTING: Retrospective observational study at a public tertiary-level hospital. METHODS: We analyzed tissue-microarray paraffin blocks of tumor tissues that had been resected from 107 patients. We used Fisher's exact test to study associations between tumor differentiation/staging and the immunoexpression of biomarkers. We also used Kaplan-Meier estimation, the log-rank test and the adjusted Cox regression model to investigate the patients' overall survival (in months) according to biomarkers and disease-free interval. RESULTS: The degree of tumor differentiation and tumor staging were not associated with the biomarkers, except in cases of patients in stages III or IV, in which there was a correlation with MLH1 expression (P=0.021). Patient survival and disease-free interval were not associated with the biomarkers. CONCLUSION: There were no associations between the degree of tumor differentiation, staging, length of survival or disease-free interval and the immunoexpression of the TS, p53, COX2, EGFR or MSH6 tumor markers. In advanced cases of colorectal adenocarcinoma (stages III and IV), there was a higher percentage of MLH1-negative results.

Prevalência da síndrome do túnel cubital em trabalhadores portuários de São Sebastião, São Paulo / Prevalence of cubital tunnel syndrome among dock workers, Saint Sebastian, São Paulo, Brazil

Introdução: Os portos brasileiros têm um papel importante na economia do país. Apesar de haver um número expressivo de trabalhadores, existem poucas pesquisas disponíveis envolvendo o ambiente portuário que relatem que as doenças musculoesqueléticas mais recorrentes correspondem as dos membros superiores, como síndrome do túnel do carpo, síndrome do manguito rotador, cervicalgia e síndrome do túnel cubital, esta definida como uma neurite causada por uma compressão do nervo ulnar no túnel cubital na região do cotovelo. Objetivo: Estimar a prevalência sugestiva da síndrome do túnel cubital no ambiente portuário. Método: Foram avaliados 72 trabalhadores portuários avulsos do OGMO do Porto de São Sebastião, São Paulo, por meio de um questionário semiestruturado, o exame clínico que incluiu a pesquisa de dor à palpação na região medial do cotovelo e a realização de duas manobras específicas para síndrome do túnel cubital, o teste provocativo de pressão e o teste de flexão máxima. Resultados: A idade média foi de 48,49 anos e um tempo médio de 23,13 anos de trabalho no porto; a síndrome do túnel cubital teve diagnóstico sugestivo em cinco dos avaliados, e apenas dois trabalhadores referiam dor no cotovelo antes e três depois do início do trabalho no porto. Conclusão: A prevalência do diagnóstico sugestivo da síndrome do túnel cubital foi de 6,9%, sendo maior entre os trabalhadores com maior tempo de trabalho (acima de um ano)

Background: Ports play a substantial role in the Brazilian economy. Despite the large number of port workers, few studies report that the most common musculoskeletal disorders among them involve the upper limbs, including carpal tunnel syndrome, rotator cuff syndrome, cervicalgia and cubital tunnel syndrome. The latter is a neuritis caused by compression of the ulnar nerve at the cubital tunnel (CuTS) on the elbow. Objective: To estimate the prevalence of a suggestive diagnosis of CuTS among port workers. Method: Seventy-two independent port workers registered with the Labor Management Organ (Órgão Gestor de Mão de Obra ­ OGMO), Port of Saint Sebastian, were evaluated based on a semi-structured questionnaire and clinical examination, including investigation of pain on palpation of the middle area of the elbow and two maneuvers specific for CuTS, namely, the pressure provocation and maximal flexion tests. Results: The average age of the participants was 48.49 years old, and their average length in the job 23.13 years. Suggestive diagnosis of CuTS was established for five participants. In only two cases elbow pain had begun before, and in three after starting work at the port. Conclusion: The prevalence of a suggestive diagnosis of CuTS was 6.9%, and was higher among the participants with longer length in the job (over one year)

Inborn-like errors of metabolism are determinants of breast cancer risk, clinical response and survival: a study of human biochemical individuality.

Breast cancer remains a leading cause of morbidity and mortality worldwide yet methods for early detection remain elusive. We describe the discovery and validation of biochemical signatures measured by mass spectrometry, performed upon blood samples from patients and controls that accurately identify (>95%) the presence of clinical breast cancer. Targeted quantitative MS/MS conducted upon 1225 individuals, including patients with breast and other cancers, normal controls as well as individuals with a variety of metabolic disorders provide a biochemical phenotype that accurately identifies the presence of breast cancer and predicts response and survival following the administration of neoadjuvant chemotherapy. The metabolic changes identified are consistent with inborn-like errors of metabolism and define a continuum from normal controls to elevated risk to invasive breast cancer. Similar results were observed in other adenocarcinomas but were not found in squamous cell cancers or hematologic neoplasms. The findings describe a new early detection platform for breast cancer and support a role for pre-existing, inborn-like errors of metabolism in the process of breast carcinogenesis that may also extend to other glandular malignancies. Statement of Significance: Findings provide a powerful tool for early detection and the assessment of prognosis in breast cancer and define a novel concept of breast carcinogenesis that characterizes malignant transformation as the clinical manifestation of underlying metabolic insufficiencies.

Prevalence of cubital tunnel syndrome among dock workers, Saint Sebastian, São Paulo, Brazil.

BACKGROUND: Ports play a substantial role in the Brazilian economy.Despite the large number of port workers, few studies report that the most common musculoskeletal disorders among them involve the upper limbs, including carpal tunnel syndrome, rotator cuff syndrome, cervicalgia and cubital tunnel syndrome.The latter is a neuritis caused by compression of the ulnar nerve at the cubital tunnel (CuTS) on the elbow. OBJECTIVE: To estimate the prevalence of a suggestive diagnosis of CuTS among port workers. METHOD: Seventy-two independent port workers registered with the Labor Management Organ (Órgão Gestor de Mão de Obra - OGMO), Port of Saint Sebastian, were evaluated based on a semi-structured questionnaire and clinical examination, including investigation of pain on palpation of the middle area of the elbow and two maneuvers specific for CuTS, namely, the pressure provocation and maximal flexion tests. RESULTS: The average age of the participants was 48.49 years old, and their average length in the job 23.13 years.Suggestive diagnosis of CuTS was established for five participants.In only two cases elbow pain had begun before, and in three after starting work at the port. CONCLUSION: The prevalence of a suggestive diagnosis of CuTS was 6.9%, and was higher among the participants with longer length in the job (over one year).

INTRODUÇÃO: Os portos brasileiros têm um papel importante na economia do país.Apesar de haver um número expressivo de trabalhadores, existem poucas pesquisas disponíveis envolvendo o ambiente portuário que relatem que as doenças musculoesqueléticas mais recorrentes correspondem as dos membros superiores, como síndrome do túnel do carpo, síndrome do manguito rotador, cervicalgia e síndrome do túnel cubital, esta definida como uma neurite causada por uma compressão do nervo ulnar no túnel cubital na região do cotovelo. OBJETIVO: Estimar a prevalência sugestiva da síndrome do túnel cubital no ambiente portuário. MÉTODO: Foram avaliados 72 trabalhadores portuários avulsos do OGMO do Porto de São Sebastião, São Paulo, por meio de um questionário semiestruturado, o exame clínico que incluiu a pesquisa de dor à palpação na região medial do cotovelo e a realização de duas manobras específicas para síndrome do túnel cubital, o teste provocativo de pressão e o teste de flexão máxima. RESULTADOS: A idade média foi de 48,49 anos e um tempo médio de 23,13 anos de trabalho no porto; a síndrome do túnel cubital teve diagnóstico sugestivo em cinco dos avaliados, e apenas dois trabalhadores referiam dor no cotovelo antes e três depois do início do trabalho no porto. CONCLUSÃO: A prevalência do diagnóstico sugestivo da síndrome do túnel cubital foi de 6,9%, sendo maior entre os trabalhadores com maior tempo de trabalho (acima de um ano).

HNF4A expression as a potential diagnostic tool to discriminate primary gastric cancer from breast cancer metastasis in a Brazilian cohort.

BACKGROUND: Among the many challenges in cancer diagnosis is the early distinction between metastatic cancer and a secondary tumor. This difficulty stems from the lack of markers that offer high sensitivity and specificity and can be easily applied in routine laboratory work. An example of this challenge is distinguishing gastric metastases originating from breast cancer from a gastric primary tumor. Hepatocyte nuclear factor 4 alpha (HNF4A) has been suggested as a potential marker in these cases. The aim of this study was to analyze the expression of HNF4A, estrogen receptor (ER), progesterone receptor (PR) and gross cystic disease fluid protein 15 (GCDFP-15) in a Brazilian cohort. METHODS: We performed immunohistochemistry analysis of HNF4A, ER, PR and GCDFP-15 in 126 patients divided into three cohorts: primary breast cancer, primary gastric cancer and both types of tumors. RESULTS: Our data confirmed the sensitivity and specificity of the HNF4A marker compared to other currently used clinical markers. CONCLUSION: HNF4A alone could be a gold standard marker for distinguishing primary gastric cancer from breast metastasis, thus validating its potential clinical use, especially in populations with high genetic diversity.

Genetic and Immunohistochemical Expression of Integrins ITGAV, ITGA6, and ITGA3 As Prognostic Factor for Colorectal Cancer: Models for Global and Disease-Free Survival.

OBJECTIVE: To evaluate the relationship between the expression profiles of 84 extracellular matrix (ECM) genes and the prognosis of patients with colorectal cancer (CRC). METHODS: This retrospective study included 114 patients with stage I-IV CRC who underwent primary tumour resection. Quantitative real-time PCR and immunohistochemistry assays were conducted using primary tumour samples. Kaplan-Meier survival curves were also generated to identify differences in global survival (GS) and disease-free survival (DFS) for the hypo- or hyperexpression status of each marker. The log-rank test was used to verify whether the differences were significant. Stepwise Cox regression models were also used to identify the risk factors associated with GS and DFS in a multivariate mode, and then were used to score the risk of death associated with each marker, either independently or in association. RESULTS: In the univariate analyses, significant differences in GS in relation to the expression profiles of ITGAV (p = 0.001), ITGA3 (p = 0.002), ITGA6 (p = 0.001), SPARC (p = 0.036), MMP9 (p = 0.034), and MMP16 (p = 0.038) were observed. For DFS, significant differences were observed in associated with ITGAV (p = 0.004) and ITGA3 (p = 0.001). However, only the ITGAV and ITGA6 gene markers for GS (hazard ratio (HR) = 3.209, 95% confidence interval (CI) = 1.412-7.293, p = 0.005 and HR = 3.105, 95% CI = 1.367-7.055, p = 0.007, respectively), and ITGA3 for DFS (HR = 3.806, 95% CI = 1.573-9.209, p = 0.003), remained in the final Cox regression models. A scoring system was developed to evaluate the risk of patient death based on the number of markers for the components of the final GS model. Scores of 0, 1, or 2 were associated with the following mean survival rates [CI]: 47.162 [44.613-49.711], 39.717 [35.471-43.964], 30.197 [24.030-36.327], respectively. CONCLUSIONS: Multivariate mathematical models demonstrated an association between hyperexpression of the ITGAV and ITGA6 integrins and GS, and also between the ITGA3 integrin and DFS, in patients with colorectal tumours. A risk scoring system based on detected hyperexpression of 0, 1, or 2 markers (e.g., ITGAV and/or ITGA6) was also found to accurately correlate with the GS curves generated for the present cohort.

Percutaneous endoscopic gastrostomy versus nasogastric tube feeding for adults with swallowing disturbances.

BACKGROUND: A number of conditions compromise the passage of food along the digestive tract. Nasogastric tube (NGT) feeding is a classic, time-proven technique, although its prolonged use can lead to complications such as lesions to the nasal wing, chronic sinusitis, gastro-oesophageal reflux, and aspiration pneumonia. Another method of infusion, percutaneous endoscopy gastrostomy (PEG), is generally used when there is a need for enteral nutrition for a longer time period. There is a high demand for PEG in patients with swallowing disorders, although there is no consistent evidence about its effectiveness and safety as compared to NGT. OBJECTIVES: To evaluate the effectiveness and safety of PEG compared with NGT for adults with swallowing disturbances. SEARCH METHODS: We searched The Cochrane Library, MEDLINE, EMBASE, and LILACS from inception to January 2014, and contacted the main authors in the subject area. There was no language restriction in the search. SELECTION CRITERIA: We planned to include randomised controlled trials comparing PEG versus NGT for adults with swallowing disturbances or dysphagia and indications for nutritional support, with any underlying diseases. The primary outcome was intervention failure (e.g. feeding interruption, blocking or leakage of the tube, no adherence to treatment). DATA COLLECTION AND ANALYSIS: We used standard methodological procedures expected by The Cochrane Collaboration. For dichotomous and continuous variables, we used risk ratio (RR) and mean difference (MD), respectively with the random-effects statistical model and 95% confidence interval (CI). We assumed statistical heterogeneity when I² > 50%. MAIN RESULTS: We included 11 randomised controlled studies with 735 participants which produced 16 meta-analyses of outcome data. Meta-analysis indicated that the primary outcome of intervention failure, occurred in lower proportion of participants with PEG compared to NGT (RR 0.18, 95% CI 0.05 to 0.59, eight studies, 408 participants, low quality evidence) and this difference was statistically significant. For this outcome, we also subgrouped the studies by endoscopic gastrostomy technique into pull, and push and not reported. We observed a significant difference favouring PEG in the pull subgroup (RR 0.07, 95% CI 0.01 to 0.35, three studies, 90 participants). Thepush subgroup contained only one clinical trial and the result favoured PEG (RR 0.05, 95% CI 0.00 to 0.74, one study, 33 participants) techniques. We found no statistically significant difference in cases where the technique was not reported (RR 0.43, 95% CI 0.13 to 1.44, four studies, 285 participants).There was no statistically significant difference between the groups for meta-analyses of the secondary outcomes of mortality (RR 0.86, 95% CI 0.58 to 1.28, 644 participants, nine studies, very low quality evidence), overall reports of any adverse event at any follow-up time point (ITT analysis, RR 0.83, 95% CI 0.51 to 1.34), 597 participants, 6 studies, moderate quality evidence), specific adverse events including pneumonia (aspiration) (RR 0.70, 95% CI 0.46 to 1.06, 645 participants, seven studies, low quality evidence), or for the meta- analyses of the secondary outcome of nutritional status including weight change from baseline, and mid-arm circumference at endpoint, although there was evidence in favour of PEG for meta-analyses of mid-arm circumference change from baseline (MD 1.16, 95% CI 1.01 to 1.31, 115 participants, two studies), and levels of serum albumin were higher in the PEG group (MD 6.03, 95% CI 2.31 to 9.74, 107 participants).For meta-analyses of the secondary outcomes of time on enteral nutrition, there was no statistically significant difference (MD 14.48, 95% CI -2.74 to 31.71; 119 participants, two studies). For meta-analyses of quality of life measures (EuroQol) outcomes in two studies with 133 participants, for inconvenience (RR 0.03, 95% CI 0.00 to 0.29), discomfort (RR 0.03, 95% CI 0.00 to 0.29), altered body image (RR 0.01, 95% CI 0.00 to 0.18; P = 0.001) and social activities (RR 0.01, 95% CI 0.00 to 0.18) the intervention favoured PEG, that is, fewer participants found the intervention of PEG to be inconvenient, uncomfortable or interfered with social activities. However, there were no significant differences between the groups for pain, ease of learning to use, or the secondary outcome of length of hospital stay (two studies, 381 participants). AUTHORS' CONCLUSIONS: PEG was associated with a lower probability of intervention failure, suggesting the endoscopic procedure may be more effective and safe compared with NGT. There is no significant difference in mortality rates between comparison groups, or in adverse events, including pneumonia related to aspiration. Future studies should include details of participant demographics including underlying disease, age and gender, and the gastrostomy technique.

Risk factors associated with outcome in liver retransplantation: multicentric study.

BACKGROUND/AIMS: To externally validate the predictive mathematical model of survival designed by Linhares et al. (2006). METHODOLOGY: This retrospective study was conducted on 217 individuals submitted to liver retransplantation from January 2000 to December 2008 in four European centers. The following variables were obtained on the recipient: age, creatinine, urgency of retransplantation and time between transplantation and retransplantation. The Kaplan-Meier survival curve and ROC curve were used to validate the mathematical model. RESULTS: The present results showed a similar pattern of survival compared to the study of Linhares et al. (2006) concerning the biological variations, when survival curves were compared for each of the four variables analyzed between both samples. When compared, the areas below the ROC curve (aROC) of derivation (0.733) and validation samples (0.593) presented significant difference (p = 0.005), revealing low relationship of sensitivity and specificity between the two curves. Similarity was observed in Kaplan-Meier survival curves. CONCLUSION: This study allowed external validation by the Kaplan-Meier survival curves of the predictive mathematical model of survival in liver retransplantation proposed by Linhares et al. (2006). However, validation through the ROC curve, the aROC, evidenced weak discrimination ability.

An evaluation of the protective effect of an infusion of chilled glucose solution on thermal injury of the bile ducts caused by radiofrequency ablation of the liver.

PURPOSE: To evaluate the protective effects of chilling the bile ducts with cold (5°C) 5% glucose solution (GS) during radiofrequency (RF) administration. METHODS: Twenty male pigs (3 mos. old; 25-30 kg) were subjected to RF delivery with chilling (experimental group, N=10) or without chilling (control group, N=10). Half of the animals in each group were euthanized immediately after the operation, and half were euthanized one week later. The following histological variables in relation to the bile ducts were evaluated by a pathologist (blind examiner): degenerative changes to the epithelium; epithelial necrosis; ulceration, regenerative changes of the epithelium; polymorphonuclear neutrophil infiltration; and thermal effects. RESULTS: The experimental group (88 bile ducts examined) showed reduced thermal damage relative to the control group (86 bile ducts examined) as demonstrated by significant differences in the following histopathological parameters: epithelial detachment of biliary epithelium (84.1% vs. 59.3%; p<0.006); elongation/palisade arrangement of nuclei (65.1% vs. 87.5%; p<0.001); pseudo-goblet cells (32.9% vs. 56.8%; p<0.001). CONCLUSION: Infusion of 5% glucose solution (5°C) has a protective effect on bile ducts subjected to heat (95-110°C, 12 min) from radiofrequency thermal ablation device.

An evaluation of the protective effect of an infusion of chilled glucose solution on thermal injury of the bile ducts caused by radiofrequency ablation of the liver

PURPOSE: To evaluate the protective effects of chilling the bile ducts with cold (5°C) 5% glucose solution (GS) during radiofrequency (RF) administration. METHODS: Twenty male pigs (3 mos. old; 25-30 kg) were subjected to RF delivery with chilling (experimental group, N=10) or without chilling (control group, N=10). Half of the animals in each group were euthanized immediately after the operation, and half were euthanized one week later. The following histological variables in relation to the bile ducts were evaluated by a pathologist (blind examiner): degenerative changes to the epithelium; epithelial necrosis; ulceration, regenerative changes of the epithelium; polymorphonuclear neutrophil infiltration; and thermal effects. RESULTS: The experimental group (88 bile ducts examined) showed reduced thermal damage relative to the control group (86 bile ducts examined) as demonstrated by significant differences in the following histopathological parameters: epithelial detachment of biliary epithelium (84.1% vs. 59.3%; p<0.006); elongation/palisade arrangement of nuclei (65.1% vs. 87.5%; p<0.001); pseudo-goblet cells (32.9% vs. 56.8%; p<0.001). CONCLUSION: Infusion of 5% glucose solution (5°C) has a protective effect on bile ducts subjected to heat (95-110°C, 12 min) from radiofrequency thermal ablation device. .

Combination chemotherapy versus single-agent chemotherapy during preoperative chemoradiation for resectable rectal cancer.

BACKGROUND: Colorectal cancer represents 10% of all cancers and is the third most common cause of death in women and men. Almost two-thirds of all bowel cancers are cancers of the colon and over one-third (34%) are cancers of the rectum, including the anus. Surgery is the cornerstone for curative treatment of rectal cancer. Mesorectal excision decreases the rate of local recurrences; however, it does not improve the overall survival of people with locally advanced rectal cancer. There have been significant research efforts since the mid-1990s to optimise the treatment of rectal cancer. Based on the findings of clinical trials, people with T3/T4 or N+ rectal tumours are now being treated preoperatively with radiation and chemotherapy, mainly fluoropyrimidine. However, the incidence of distant metastases remains as high as 30%. Combination chemotherapy regimens, similar to those used in metastatic disease with the addition of oxaliplatin and irinotecan, have been tested to improve the prognosis of people with rectal cancer. OBJECTIVES: To compare outcomes (including overall survival, disease-free survival and toxicity) between two 5-fluorouracil-containing chemotherapy regimens in people with stage II and III rectal cancer who are receiving preoperative chemoradiation. SEARCH METHODS: We searched the Cochrane Colorectal Cancer Group Specialised Register (January 2015), the Cochrane Central Register of Controlled Trials (2015, Issue 1), Ovid MEDLINE (1950 to January 2015), Ovid EMBASE (1974 to January 2015) and LILACS (1982 to January 2015). We reviewed the reference lists of included studies, checked clinical trials registers and handsearched relevant journal proceedings. We applied no language or publication restrictions. SELECTION CRITERIA: Randomised controlled trials (RCTs) comparing single-agent chemotherapy (fluoropyrimidine) versus combination chemotherapy (fluoropyrimidine plus another agent including, but not limited to, oxaliplatin) during preoperative radiochemotherapy in people with resectable rectal cancer. DATA COLLECTION AND ANALYSIS: Two review authors (HMR, EMKS) independently extracted data and assessed trial quality. When necessary, we requested additional information and clarification of published data from the authors of individual trials. MAIN RESULTS: We included four RCTs involving 3875 people with resectable rectal cancer. In the preoperative period, the participants of these studies were randomised to receive chemoradiation either with a single fluoropyrimidine agent (capecitabine or 5-fluorouracil) or with a combination of drugs (fluoropyrimidine plus oxaliplatin). The only study that reported overall survival and disease-free survival found no significant differences between the intervention and control groups; we considered this evidence very low quality. For pathological complete response after preoperative treatment (ypCR) there was high quality evidence favouring the intervention group (odds ratio (OR) 1.23, 95% confidence interval (CI) 1.04 to 1.46), but there was also moderate quality evidence suggesting a higher risk for early toxicity in the intervention group (OR 2.07, 95% CI 1.31 to 3.27). Moderate to high quality evidence suggested that the control group had better compliance to radiotherapy (OR 0.32, 95% CI 0.14 to 0.75). There were no significant differences between groups in postoperative mortality within 60 days, postoperative morbidity, resection margins, abdominoperineal resection and Hartmann procedures. AUTHORS' CONCLUSIONS: There was very low quality evidence that people with resectable rectal cancer who receive combination preoperative chemotherapy have no improvements in overall survival or disease-free survival. There was high quality evidence that suggested that combination chemotherapy with oxaliplatin may improve local tumour control in people with resectable rectal cancer, but this regimen also caused more toxicity. The review included four RCTs but only one reported survival; therefore, we cannot make robust conclusions or useful clinical recommendations. The publication of more survival data from these studies will contribute to future analyses.

ANTECEDENTES: El cáncer colorrectal representa el 10% de todos los cánceres y es la tercera causa más frecuente de muerte en mujeres y hombres. Casi dos tercios de todos los cánceres intestinales son cánceres de colon y más de un tercio (34%) son cánceres del recto, incluido el ano. La cirugía es la base del tratamiento curativo del cáncer rectal. La escisión mesorrectal disminuye la tasa de recidivas locales; sin embargo, no mejora la supervivencia general de las personas con cáncer de recto localmente avanzado. Desde mediados de los años noventa se han realizado esfuerzos significativos de investigación para optimizar el tratamiento del cáncer rectal. Según los resultados de los ensayos clínicos, actualmente las personas con tumores rectales T3/T4 o N+ se tratan preoperatoriamente con radiación y quimioterapia, principalmente fluoropirimidina. Sin embargo, la incidencia de metástasis distantes todavía es tan alta como del 30%. Para mejorar el pronóstico de las personas con cáncer rectal se han probado regímenes de quimioterapia combinada, similares a los utilizados en la enfermedad metastásica con el agregado de oxaliplatino e irinotecán. OBJETIVOS: Comparar los desenlaces (incluida la supervivencia general, la supervivencia sin enfermedad y la toxicidad) entre dos regímenes de quimioterapia que contienen 5­fluorouracilo en personas con cáncer rectal estadio II y III que reciben quimiorradioterapia preoperatoria. MÉTODOS DE BÚSQUEDA: Se hicieron búsquedas en el Registro especializado del Grupo Cochrane Colorrectal (Cochrane Colorectal Cancer Group) (enero de 2015), Registro Cochrane central de ensayos controlados (Cochrane Central Register of Controlled Trials) (2015, número 1), Ovid MEDLINE (1950 hasta enero de 2015), Ovid EMBASE (1974 hasta enero de 2015) y en LILACS (1982 hasta enero de 2015). Se revisaron las listas de referencias de los estudios incluidos, se verificaron los registros de ensayos clínicos y se hicieron búsquedas manuales en los resúmenes de revistas relevantes. No se aplicaron restricciones de idioma ni de publicación. CRITERIOS DE SELECCIÓN: Ensayos controlados aleatorizados (ECA) que compararon la quimioterapia de agente único (fluoropirimidina) versus la quimioterapia combinada (fluoropirimidina más otro agente que incluyó, pero no se limitó a oxaliplatino) durante la radioquimioterapia preoperatoria en personas con cáncer rectal resecable. OBTENCIÓN Y ANÁLISIS DE LOS DATOS: Dos autores de la revisión (HMR, EMKS) de forma independiente extrajeron los datos y evaluaron la calidad de los ensayos. Cuando fue necesario, se solicitó información adicional y aclaraciones sobre los datos publicados de los autores de los ensayos individuales. RESULTADOS PRINCIPALES: Se incluyeron cuatro ECA con 3875 personas con cáncer rectal resecable. En el período preoperatorio, los participantes de estos estudios se asignaron al azar a recibir quimiorradioterapia con el agente único fluoropirimidina (capecitabina o 5­fluorouracilo) o con una combinación de fármacos (fluoropirimidina más oxaliplatino). El único estudio que informó sobre la supervivencia general y la supervivencia sin enfermedad no encontró diferencias significativas entre los grupos de intervención y control; esta evidencia se consideró de calidad muy baja. Para la respuesta patológica completa después del tratamiento preoperatorio (ypCR) hubo evidencia de calidad alta a favor del grupo de intervención (odds ratio [OR] 1,23; intervalo de confianza [IC] del 95%: 1,04 a 1,46), pero también hubo evidencia de calidad moderada que indicó un mayor riesgo de toxicidad temprana en el grupo de intervención (OR 2,07; IC del 95%: 1,31 a 3,27). Evidencia de calidad moderada a alta indicó que el grupo control tuvo un mejor cumplimiento de la radioterapia (OR 0,32; IC del 95%: 0,14 a 0,75). No hubo diferencias significativas entre los grupos en la mortalidad posoperatoria en el transcurso de 60 días, la morbilidad posoperatoria, los márgenes de resección, la resección abdominoperineal ni los procedimientos de Hartmann. CONCLUSIONES DE LOS AUTORES: Hubo evidencia de calidad muy baja de que las personas con cáncer rectal resecable que reciben quimioterapia combinada preoperatoria no tienen mejorías en la supervivencia general ni la supervivencia sin enfermedad. Hubo evidencia de calidad alta que indicó que la quimioterapia combinada con oxaliplatino podría mejorar el control tumoral local en las personas con cáncer rectal resecable, pero este régimen también provocó más toxicidad. La revisión incluyó cuatro ECA, pero sólo uno informó sobre la supervivencia; por lo tanto, no se pueden establecer conclusiones sólidas ni recomendaciones clínicas útiles. La publicación de más datos de la supervivencia de estos estudios contribuirá a futuros análisis.

Using computed tomography colonography in patients at high risk of colorectal cancer - a prospective study in a university hospital in South America.

OBJECTIVES: The purpose of our study was to report the results of the implementation of computed tomography colonography in a university hospital setting serving a Brazilian population at high risk of colorectal cancer. METHODS: After creating a computed tomography colonography service in our institution, 85 patients at high risk of colorectal cancer underwent computed tomography colonography followed by a same-day optical colonoscopy from September 2010 to May 2012. The overall accuracy of computed tomography colonography in the detection of lesions ≥6 mm was compared to that of optical colonoscopy (direct comparison). All colonic segments were evaluated using quality imaging (amount of liquid and solid residual feces and luminal distension). To assess patient acceptance and preference, a questionnaire was completed before and after the computed tomography colonography and optical colonoscopy. Fisher's exact test was used to measure the correlations between colonic distension, discomfort during the exam, exam preference and interpretation confidence. RESULTS: Thirteen carcinomas and twenty-two lesions ≥6 mm were characterized. The sensitivity, specificity and accuracy of computed tomography colonography were 100%, 98.2% and 98.6%, respectively. Computed tomography colonography was the preferred method of investigation for 85% of patients. The preparation was reported to cause only mild discomfort for 97.6% of patients. According to the questionnaires, there was no significant relationship between colonic distension and discomfort (p>0.05). Most patients (89%) achieved excellent bowel preparation. There was a statistically significant correlation between the confidence perceived in reading the computed tomography colonography and the quality of the preparation in each colonic segment (p≤0.001). The average effective radiation dose per exam was 7.8 mSv. CONCLUSION: It was possible to institute an efficient computed tomography colonography service at a university hospital that primarily assists patients from the public health system, with high accuracy, good acceptance and effective radiation doses. Our results seem to be comparable to other centers of excellence and fall within acceptable published guidelines, showing that a successful computed tomography colonography program can be reproduced in a South American population screened in a university hospital.

Using computed tomography colonography in patients at high risk of colorectal cancer - a prospective study in a university hospital in South America

OBJECTIVES: The purpose of our study was to report the results of the implementation of computed tomography colonography in a university hospital setting serving a Brazilian population at high risk of colorectal cancer. METHODS: After creating a computed tomography colonography service in our institution, 85 patients at high risk of colorectal cancer underwent computed tomography colonography followed by a same-day optical colonoscopy from September 2010 to May 2012. The overall accuracy of computed tomography colonography in the detection of lesions ≥6 mm was compared to that of optical colonoscopy (direct comparison). All colonic segments were evaluated using quality imaging (amount of liquid and solid residual feces and luminal distension). To assess patient acceptance and preference, a questionnaire was completed before and after the computed tomography colonography and optical colonoscopy. Fisher's exact test was used to measure the correlations between colonic distension, discomfort during the exam, exam preference and interpretation confidence. RESULTS: Thirteen carcinomas and twenty-two lesions ≥6 mm were characterized. The sensitivity, specificity and accuracy of computed tomography colonography were 100%, 98.2% and 98.6%, respectively. Computed tomography colonography was the preferred method of investigation for 85% of patients. The preparation was reported to cause only mild discomfort for 97.6% of patients. According to the questionnaires, there was no significant relationship between colonic distension and discomfort (p>0.05). Most patients (89%) achieved excellent bowel preparation. There was a statistically significant correlation between the confidence perceived in reading the computed tomography colonography and the quality of the preparation in each colonic segment (p≤0.001). The average effective radiation dose per exam was 7.8 mSv. CONCLUSION: It was possible to institute an efficient computed ...

Overexpression of the ITGAV gene is associated with progression and spread of colorectal cancer.

BACKGROUND/AIM: The interaction of neoplastic cells with the extracellular matrix is a critical event for the initiation of cancer invasion and metastasis. We evaluated the relationship between the expression of SPARC, ITGAV, THBS1 and VCAM-1 genes of extracellular matrix in the progression and dissemination of colorectal cancer (CRC). PATIENTS AND METHODS: Adult patients (N=114) underwent resection of CRC. Gene expression in CRC was determined by quantitative real-time polymerase chain reaction (PCR). Protein expression was analyzed by immunohistochemistry (IHC). Correlation with pathway-related molecules (p53, Bcl-2, Ki-67, EGFR and VEGF) was assessed. RESULTS: Tumors with perineural invasion showed overexpression (p=0.028) of the ITGAV gene with regard to cancers without perineural invasion and validation of the result through IHC expression of the corresponding proteins, was significant for the expression of ITGAV protein (p=0.001). CONCLUSION: The overexpression of ITGAV gene was associated with higher progression and spread of CRC via perineural invasion.

Association between human Papillomavirus and colorectal adenocarcinoma and its influence on tumor staging and degree of cell differentiation.

BACKGROUND: Colorectal cancer is one of the most common types of neoplasia among the worldwide adult population. Among neoplasms of the gastrointestinal tract, it is ranked second in relation to prevalence and mortality, but its etiology is only known in around 5% of the cases. It is believed that 15% of malignant diseases are related to viral oncogenesis. AIM: To correlate the presence of HPV with the staging and degree of cell differentiation among patients with colorectal adenocarcinoma. METHODS: A retrospective case-control study was conducted on 144 patients divided between a test group of 79 cases of colorectal cancer and a control group to analyze 144 patients aged 25 to 85 years (mean, 57.85 years; standard deviation, 15.27 years and median, 58 years). Eighty-six patients (59.7%) were male. For both groups, tissue samples from paraffin blocks were subjected to DNA extraction followed by the polymerase chain reaction using generic and specific primers for HPV 16 and 18. Dot blot hybridization was also performed with the aim of identifying HPV DNA. RESULTS: The groups were shown to be homogenous regarding sex, age and site of HPV findings in the samples analyzed. Out of the 41 patients with HPV, 36 (45.6%) were in the cases and five (7.7%) were in the control group (p<0.001). All the HPV cases observed comprised HPV 16, and HPV 18 was not shown in any of the cases studied. There were no significant differences in comparisons of sex, age and site regarding the presence of HPV in either of the groups. It was not observe any significant difference in relation to staging or degree of cell differentiation among the patients with colorectal cancer. CONCLUSION: Human papillomavirus type 16 is present in individuals with colorectal carcinoma. However, its presence was unrelated to staging or degree of differentiation.

Association between human Papillomavirus and colorectal adenocarcinoma and its influence on tumor staging and degree of cell differentiation / Associação do Papilomavírus humano com o adenocarcinoma colorretal e sua influência no estadio tumoral e no grau de diferenciação celular

BACKGROUND: Colorectal cancer is one of the most common types of neoplasia among the worldwide adult population. Among neoplasms of the gastrointestinal tract, it is ranked second in relation to prevalence and mortality, but its etiology is only known in around 5% of the cases. It is believed that 15% of malignant diseases are related to viral oncogenesis. AIM: To correlate the presence of HPV with the staging and degree of cell differentiation among patients with colorectal adenocarcinoma. METHODS: A retrospective case-control study was conducted on 144 patients divided between a test group of 79 cases of colorectal cancer and a control group to analyze 144 patients aged 25 to 85 years (mean, 57.85 years; standard deviation, 15.27 years and median, 58 years). Eighty-six patients (59.7%) were male. For both groups, tissue samples from paraffin blocks were subjected to DNA extraction followed by the polymerase chain reaction using generic and specific primers for HPV 16 and 18. Dot blot hybridization was also performed with the aim of identifying HPV DNA. RESULTS: The groups were shown to be homogenous regarding sex, age and site of HPV findings in the samples analyzed. Out of the 41 patients with HPV, 36 (45.6%) were in the cases and five (7.7%) were in the control group (p<0.001). All the HPV cases observed comprised HPV 16, and HPV 18 was not shown in any of the cases studied. There were no significant differences in comparisons of sex, age and site regarding the presence of HPV in either of the groups. It was not observe any significant difference in relation to staging or degree of cell differentiation among the patients with colorectal cancer. CONCLUSION: Human papillomavirus type 16 is present in individuals with colorectal carcinoma. However, its presence was unrelated to staging or degree of differentiation. .

RACIONAL: O câncer colorretal é uma das neoplasias mais frequentes entre a população adulta mundial, e entre as do trato gastrointestinal, é a segunda em relação à prevalência e mortalidade sendo a sua causa conhecida apenas em cerca de 5% dos casos. Acredita-se que 15% das doenças malignas estariam relacionadas à oncogênese viral. OBJETIVO: Correlacionar a presença do HPV com o estadiamento e o grau de diferenciação celular dos pacientes portadores de adenocarcinoma colorretal. MÉTODOS: Foi realizado um estudo retrospectivo do tipo caso-controle com 144 pacientes divididos em um grupo teste representado por pacientes com câncer colorretal em um total de 79 casos e um grupo controle correspondente à pacientes com doença benigna totalizando 65 casos. Após a aplicação dos critérios de exclusão, foi possível analisar 144 pacientes com idade entre 25 a 85 anos (média de 57,85 anos com desvio-padrão de 15,27 anos e mediana de 58 anos). Oitenta e seis (59,7%) pacientes eram homens. Amostras teciduais a partir de blocos de parafina de ambos os grupos foram submetidos à extração do DNA e em seguida foi realizada reação em cadeia da polimerase com iniciadores genéricos e específicos para HPV 16 e 18 e também a hibridização do tipo dot blot com o intuito de identificar o DNA do HPV. RESULTADOS: Os grupos se mostraram homogêneos quanto a sexo, idade e localização do HPV nas amostras analisadas. Dos 41 pacientes com HPV, 36 (45,6%) eram do grupo teste e cinco (7,7%) do grupo controle (p<0,001). Todos os casos de HPV observados correspondiam ao HPV 16 não sendo evidenciado HPV 18 em nenhum caso estudado. Não houve diferença significativa na comparação realizada quando se considerou o sexo, idade e localização ...