Time after ostomy surgery and type of treatment are associated with quality of life changes in colorectal cancer patients with colostomy.

PURPOSE: Quality of life in colorectal cancer patients may be affected by colostomy and treatment, but relevant studies are still scarce and contradictory. The present study aimed to evaluate the association between colostomy time and treatment type with quality of life in colorectal cancer patients. METHODS: A prospective observational study of 41 patients with colorectal cancer was conducted on three occasions T0, T1 and T2 (0-2; 3-5 and 6-8 months after ostomy surgery, respectively). The treatments prescribed were: surgery alone, chemotherapy or radiotherapy, or chemoradiotherapy. European Organization for Research and Treatment of Cancer questionnaires were used to evaluate quality of life. Worsening clinical changes were evaluated considering difference in scores between times of surgery ≥±9 points. RESULTS: Regarding ostomy surgery, scores in physical function improved between T0 and T1 and these better scores were maintained at T1 to T2. The same was observed for urinary frequency, appetite loss and dry mouth. Chemoradiotherapy was associated with worse scores for global health status, nausea and vomiting, bloating and dry mouth. Although significant differences were not observed in some domains in the Generalized Estimating Equations analysis, patients showed noticeable changes for the worse in the pain, anxiety, weight concern, flatulence and embarrassment domains during these periods. CONCLUSIONS: Colostomy improved quality of life at 3-5 months in most domains of quality of life and remained better at 6-8 months after surgery. Chemoradiotherapy had a late negative influence on quality of life. Health teams could use these results to reassure patients that this procedure will improve their quality of life in many functional and symptomatic aspects.

Ostomy time and nutrition status were associated on quality of life in patients with colorectal cancer / Tempo de estomia e estado nutricional são associados com a qualidade de vida em pacientes com câncer colorretal

ABSTRACT Introduction: Colorectal cancer frequency increases each year and consequently the number of ostomies, a procedure that helps in the treatment of colorectal cancer but has an impact on quality of life. Studies evaluating the impact of ostomy time and nutritional status on the quality of life of colostomized patients with colorectal cancer are scarce in the literature. So, the aim of this study was to evaluate the association ostomy time and nutritional status on quality of life in colostomized colorectal cancer patients. Methods: A cross-sectional study was conducted with 97 colostomized patients due to colorectal cancer from a reference service. Socioeconomic, demographic, clinical data were obtained. European Organisation for Research and Treatment of Cancer questionnaires EORTC-QLQ30 and EORTC-QLQ-CR29 were used to analyse the quality of life. Statistical significance analysis was performed using the Wilcoxon's non-parametric or Chi-Square test. Results: Of the 97 individuals, 50.5% were female, 64.9% were over 60 years old, 67.4% have ostomy for less than 1 year. Half of the patients had some nutritional status inadequacy: 24.2% were malnourished, 17.9% overweight and 8.4% obese. Shorter ostomy time was associated with role function, blood or mucus in stools, stoma care problems and men's sexual interest, while malnutrition was associated with concern about weight. Conclusions: Ostomy time and nutrition status were associated with quality of life in some domains, such as role function, insomnia, appetite loss, abdominal pain, buttock pain, bloating, hair loss, taste loss have an impact together with the nutritional status on the quality of life in patients colostomized colorectal cancer.

RESUMO Introdução: A frequência do câncer colorretal aumenta a cada ano e, consequentemente, aumenta o número de estomias, procedimento que auxilia no tratamento do câncer colorretal, porém impacta na qualidade de vida. Estudos que avaliam o impacto do tempo de estomia e do estado nutricional na qualidade de vida de pacientes colostomizados com câncer colorretal são escassos na literatura. Assim, o objetivo deste estudo foi avaliar a associação entre tempo de estomia e estado nutricional e qualidade de vida em pacientes colostomizados por câncer colorretal. Métodos: Participaram deste estudo transversal 97 pacientes colostomizados por câncer colorretal de um serviço de referência. Dados socioeconômicos, demográficos e clínicos foram obtidos. Os questionários da Organização Europeia para Pesquisa e Tratamento do Câncer EORTC-QLQ30 e EORTC-QLQ-CR29 foram utilizados para analisar a qualidade de vida. A análise de significância estatística foi realizada usando o teste não paramétrico Wilcoxon ou teste Qui-Quadrado. Resultados: Dos 97 indivíduos, 50.,5% eram do sexo feminino, 64.,9% tinham mais de 60 anos, 67.,4% com estomia há menos de 1 ano. Metade dos pacientes apresentava inadequação do estado nutricional: 24.,2% estavam desnutridos, 17.,9% sobrepeso e 8,4% obesos. O menor tempo de estomia foi associado ao desempenho funcional, sangue ou muco nas fezes, problemas em cuidar da estomia e interesse sexual dos homens, enquanto a desnutrição foi associada à preocupação com o peso. Conclusão: A cirurgia de estomia esteve associada à qualidade de vida em alguns domínios, como desempenho funcional, insônia, perda de apetite, dor abdominal, dor nas nádegas, perda de cabelo, perda do paladar, e tem um impacto junto ao estado nutricional da qualidade de vida em pacientes colostomizados por câncer colorretal.

Rat postnatal prostate development is impaired by in vitro high-glucose environment.

The prostate development has an important postnatal period where cell proliferation begins at the first days after birth and is related to gland growth and ramification. Any metabolic and/or hormonal changes occurring during the postnatal period can interfere with prostate branching. Hyperglycemia is a common condition in low-weight preterm babies at neonatal period and also a disorder found in the offspring of obese mothers. Thus, this study aimed to investigate the in vitro effects of a glucose-rich environment during prostate postnatal development. Wistar rats prostate were removed at birth and cultured for 1, 2 and 3 days in DMEM under normal (5.5 mM) or elevated (7 and 25 mM) glucose concentrations. Samples were processed for morphological analysis, PCNA and smooth muscle α-actin immunohistochemistry, evaluation of active caspase-3, ERK1/2 and Wnt5a gene expression. High glucose concentrations reduced the number of prostatic buds and proliferating cells. The natural increase in smooth muscle cells and collagen deposition observed in control prostates during the first 3 days of development was reduced by elevated glucose concentrations. The amount of active caspase-3 was higher in prostates incubated at 7 mM and TGF-ß levels also increased sharply after both glucose concentrations. Additionally, high glucose environment decreased ERK 1/2 activation and increased Wnt5a expression. These data show that high levels of glucose during the first postnatal days affected prostate development by inhibiting cell proliferation which impairs bud branching and this was associated with anti-proliferative signals such as decreased ERK1/2 activation and increased Wnt5a expression.

Effect of glucose and palmitate environment on proliferation and migration of PC3-prostate cancer cells.

Recent studies have been trying to find out how diet and metabolic changes such as dyslipidaemia, hyperglycaemia, and hyperinsulinaemia can stimulate cancer progression. This investigation aimed to evaluate the effect of high concentrations of fatty acids and/or glucose in tumour prostate cells, focusing on the proliferation/migration profile and oxidative stress. PC3 cells were treated with high concentration of saturated fatty acid (palmitate, 100 µM), glucose (220 mg/dL), or both for 24 or 48 h. Results demonstrated that PC3 cells showed a significant increase in proliferation after 48 h of treatment with glucose and palmitate+glucose. Cell proliferation was associated with reduced levels of AMPK phosphorylation in glucose group at 24 and 48 h of treatment, while palmitate group presented this result only after 48 h of treatment. Also, there was a significant increase in cell migration between time 0 and 48 h after all treatments, except in the control. Catalase activity was increased by palmitate in the beginning of treatment, while glucose presented a later effect. Also, nitrite production was increased by glucose only after 48 h, and the total antioxidant activity was enhanced by palmitate in the initial hours. Thus, we conclude that the high concentration of the saturated fatty acid palmitate and glucose in vitro influences PC3 cells and stimulates cellular activities related to carcinogenesis such as cell proliferation, migration, and oxidative stress in different ways. Palmitate presents a rapid and initial effect, while a glucose environment stimulates cells later on, maintaining high levels of cell proliferation.

Role of the TNF-α receptor type 1 on prostate carcinogenesis in knockout mice.

BACKGROUND: TNF-α is a key cytokine involved in prostate carcinogenesis and is mediated by the TNF-α receptor type 1 (TNFR-1). This receptor triggers two opposite pathways: cell death or cell survival and presents a protective or stimulator role in cancer. Thus, the purpose of this study was to evaluate the role of TNF signaling in chemically induced prostate carcinogenesis in mice. METHODS: C57bl/6 wild type (WT) and p55 TNFR-1 knockout mice (KO) were treated with mineral oil (control) or N-methyl N-nitrosurea (MNU) in association with testosterone (MNU+T, single injection of 40 mg/kg and weekly injection 2 mg/kg, respectively) over the course of 6 months. After this induction period, prostate samples were processed for histological and biochemical analysis. RESULTS: MNU+T treatment led to the development of prostate intraepithelial neoplasia (PIN) and adenocarcinoma (PCa) in both WT and KO animals; however, the incidence of PCa was lower in KO group than in WT. Cell proliferation analysis showed that PCNA levels were significantly lower in the KO group, even after carcinogenesis induction. Furthermore, the prostate of KO animals had lower levels of p65 and p-mTOR after treatment with MNU+T than WT. There was also a decrease in prostate androgen receptor levels after induction of carcinogenesis in both KO and WT mice. Regarding the extracellular matrix in the prostate, KO mice had higher levels of fibronectin and lower levels of matrix metalloproteinase 2 (MMP2) after carcinogenesis. Finally, there was a similar increase in apoptosis in both groups after carcinogenesis, indicating that the TNAFr1 pathway in prostate carcinogenesis presented proliferative, and not apoptotic, stimuli. CONCLUSIONS: TNF-α, through its receptor TNFR-1, promoted cell proliferation and cell survival in prostate by activation of the AKT/mTOR and NFKB pathway, which stimulated prostate carcinogenesis in chemically induced mice. Prostate 76: 917-926, 2016. © 2016 Wiley Periodicals, Inc.