Patients’ related sexual outcomes in colorectal surgery

BackgroundPatients undergoing colorectal surgery (CRS) have an increased risk of developing sexual disorders, attributed to different mechanisms. In this context, sexual function (SF) assessment of patients before and after surgery is essential: to identify risk factors for sexual disorders as well as to minimize their impact on overall quality of life (QoL), allowing them a satisfying relationship and sexual life.Material and methodsPatients over 18 years of age who underwent a CRS in the University Hospital of Geneva, Switzerland, between June 2014 and February 2016 were included. Our main objective was to compare and analyze the evolution of SF, QoL, and marital satisfaction (MS) before and after CRS. Specific and standardized tests were used.ResultsA cohort of 72 patients with a median age of 58.73 was analyzed. The majority of CRS was elective (91.5%). A percentage of 52.8% of patients underwent surgery for oncological reasons. There was no statistical difference in SF, sexual QoL, and MS before and after elective or emergency CRS for men. Interestingly, a significant decrease in women’s SF (FSFI) as well as their satisfaction within their couple (Locke–Wallace) until 12 months after surgery was found (p = 0.021). However, they showed a steady SF (GRISS) within their couple until 12 months after surgery.ConclusionRegarding knowledge about difficulties to talk about this intimate topic and gender differences, this general overview raises the question of the necessity to introduce in a long-course follow-up different methods of sexual health assessment with specific stakeholders

De la caractérisation des Cellules Initiant le Cancer Colorectal vers un biomarqueur pronostique et de surveillance des sujets traités pour cancer colorectal

The ColoRectal Cancer (CCR) is the second leading cause of cancer mortality in the world. The risk of recurrence after curative treatment reaches 45% for stages 3. One of the hypotheses currently able to explain the metastatic process and the recurrences is the presence within it of "stem" cells, which can "initiate" the cancer. Our reflection is in line with the work carried out in our Laboratory, entitled "Strategies for the isolation and characterization of cells that initiate colorectal cancer" (Mélin et al, 2012).In the first part, our work focused on in vitro analysis of the sensitivity of fractions enriched in CIC to different chemotherapy molecules most commonly used in colorectal cancer (CRC). Then, in a second part, the analysis of the tumors obtained after transplantation was made ex ovo on Chicken Embryo Chorio-Allantoid Membrane (CAM), an easily manipulated model, inexpensive and very fast. This model provides information on the key phenomena of tumorigenesis and neoangiogenesis. Analyzes of tumor growth, histology (proliferation, apoptosis and vascularization) and protein analyzes were carried out in parallel. From this last study, a particular marker, E cadherin, was highlighted as an indirect link with witness of aggressiveness. Indeed, within the tumors obtained from F1 HCT116, the chemosensitive fraction, the expression of cadherin E was increased in contrast to the tumors obtained from F3 WiDr, chemoresistant fraction, showing a decrease in expression of E cadherin.Thus, in a third part, knowing that a link between cells initiating cancer and E cadherin was highlighted, we focused on its expression. We first studied its expression in vitro on 5 Fluorouracilresistant cells. Its expression was then studied ex vivo in tissues and sera of operated patients of CRC.Le Cancer Colo Rectal (CCR) est la deuxième cause de mortalité par cancer dans le monde. Le risque de récidive après traitement curatif atteint 45% pour les stades 3. Une des hypothèses à l’heure actuelle pouvant expliciter le processus métastatique et les récidives est la présence en son sein de cellules « souches », pouvant « initier » le cancer. Notre réflexion s’inscrit dans la continuité des travaux réalisés au sein de notre Laboratoire, intitulés «Stratégies d’isolement et de caractérisation des cellules initiatrices de cancer colorectal», (Mélin et al, 2012). Dans une première partie, notre travail a porté sur l’analyse in vitro de la sensibilité des fractions enrichies en CIC aux différentes molécules de chimiothérapie les plus couramment utilisées en cancérologie colorectale.Puis, dans une deuxième partie, l’analyse des tumeurs obtenues après greffe a été faite ex ovo sur la Membrane Chorio-Allantoïdienne d’embryon de poulet (CAM), modèle facilement manipulable, peu onéreux et très rapide. Ce modèle étant naturellement immunodéprimé, il permet d’obtenir des informations concernant les phénomènes clés de la tumorigénèse et de la néoangiogénèse. Des analyses de la croissance tumorale, de l’histologie (prolifération, apoptose et vascularisation) et des analyses protéiques ont été menées en parallèle. De cette dernière étude, un marqueur particulier la E cadhérine, a été mis en évidence comme témoin indirect d’agressivité. En effet, au sein des tumeurs obtenues à partir de F1 HCT116, fraction himiosensible, l’expression de la E cadhérine est augmentée contrairement aux tumeurs obtenues à partir de F3 WiDr, fraction chimiorésistante, montrant une diminution d’expression de la E cadhérine.Ainsi, dans une troisième partie, sachant qu’un lien entre cellules initiant le cancer et E cadhérine a été mis en évidence, nous nous sommes focalisés sur son expression. Nous avons alors étudié son expression in vitro sur des cellules résistantes au 5 Fluorouracile. Puis, son expression a été étudiée ex vivo au sein de tissus et de sérums de patients opérés de cancer colorectal

De la caractérisation des Cellules Initiant le Cancer Colorectal vers un biomarqueur pronostique et de surveillance des sujets traités pour cancer colorectal

The ColoRectal Cancer (CCR) is the second leading cause of cancer mortality in the world. The risk of recurrence after curative treatment reaches 45% for stages 3. One of the hypotheses currently able to explain the metastatic process and the recurrences is the presence within it of "stem" cells, which can "initiate" the cancer. Our reflection is in line with the work carried out in our Laboratory, entitled "Strategies for the isolation and characterization of cells that initiate colorectal cancer" (Mélin et al, 2012).In the first part, our work focused on in vitro analysis of the sensitivity of fractions enriched in CIC to different chemotherapy molecules most commonly used in colorectal cancer (CRC). Then, in a second part, the analysis of the tumors obtained after transplantation was made ex ovo on Chicken Embryo Chorio-Allantoid Membrane (CAM), an easily manipulated model, inexpensive and very fast. This model provides information on the key phenomena of tumorigenesis and neoangiogenesis. Analyzes of tumor growth, histology (proliferation, apoptosis and vascularization) and protein analyzes were carried out in parallel. From this last study, a particular marker, E cadherin, was highlighted as an indirect link with witness of aggressiveness. Indeed, within the tumors obtained from F1 HCT116, the chemosensitive fraction, the expression of cadherin E was increased in contrast to the tumors obtained from F3 WiDr, chemoresistant fraction, showing a decrease in expression of E cadherin.Thus, in a third part, knowing that a link between cells initiating cancer and E cadherin was highlighted, we focused on its expression. We first studied its expression in vitro on 5 Fluorouracilresistant cells. Its expression was then studied ex vivo in tissues and sera of operated patients of CRC.Le Cancer Colo Rectal (CCR) est la deuxième cause de mortalité par cancer dans le monde. Le risque de récidive après traitement curatif atteint 45% pour les stades 3. Une des hypothèses à l’heure actuelle pouvant expliciter le processus métastatique et les récidives est la présence en son sein de cellules « souches », pouvant « initier » le cancer. Notre réflexion s’inscrit dans la continuité des travaux réalisés au sein de notre Laboratoire, intitulés «Stratégies d’isolement et de caractérisation des cellules initiatrices de cancer colorectal», (Mélin et al, 2012). Dans une première partie, notre travail a porté sur l’analyse in vitro de la sensibilité des fractions enrichies en CIC aux différentes molécules de chimiothérapie les plus couramment utilisées en cancérologie colorectale.Puis, dans une deuxième partie, l’analyse des tumeurs obtenues après greffe a été faite ex ovo sur la Membrane Chorio-Allantoïdienne d’embryon de poulet (CAM), modèle facilement manipulable, peu onéreux et très rapide. Ce modèle étant naturellement immunodéprimé, il permet d’obtenir des informations concernant les phénomènes clés de la tumorigénèse et de la néoangiogénèse. Des analyses de la croissance tumorale, de l’histologie (prolifération, apoptose et vascularisation) et des analyses protéiques ont été menées en parallèle. De cette dernière étude, un marqueur particulier la E cadhérine, a été mis en évidence comme témoin indirect d’agressivité. En effet, au sein des tumeurs obtenues à partir de F1 HCT116, fraction himiosensible, l’expression de la E cadhérine est augmentée contrairement aux tumeurs obtenues à partir de F3 WiDr, fraction chimiorésistante, montrant une diminution d’expression de la E cadhérine.Ainsi, dans une troisième partie, sachant qu’un lien entre cellules initiant le cancer et E cadhérine a été mis en évidence, nous nous sommes focalisés sur son expression. Nous avons alors étudié son expression in vitro sur des cellules résistantes au 5 Fluorouracile. Puis, son expression a été étudiée ex vivo au sein de tissus et de sérums de patients opérés de cancer colorectal

From characterization of colorectal cancer initiating cells to a prognostic biomarker and monotoring of patients treated for colorectal cancer

Le Cancer Colo Rectal (CCR) est la deuxième cause de mortalité par cancer dans le monde. Le risque de récidive après traitement curatif atteint 45% pour les stades 3. Une des hypothèses à l’heure actuelle pouvant expliciter le processus métastatique et les récidives est la présence en son sein de cellules « souches », pouvant « initier » le cancer. Notre réflexion s’inscrit dans la continuité des travaux réalisés au sein de notre Laboratoire, intitulés «Stratégies d’isolement et de caractérisation des cellules initiatrices de cancer colorectal», (Mélin et al, 2012). Dans une première partie, notre travail a porté sur l’analyse in vitro de la sensibilité des fractions enrichies en CIC aux différentes molécules de chimiothérapie les plus couramment utilisées en cancérologie colorectale.Puis, dans une deuxième partie, l’analyse des tumeurs obtenues après greffe a été faite ex ovo sur la Membrane Chorio-Allantoïdienne d’embryon de poulet (CAM), modèle facilement manipulable, peu onéreux et très rapide. Ce modèle étant naturellement immunodéprimé, il permet d’obtenir des informations concernant les phénomènes clés de la tumorigénèse et de la néoangiogénèse. Des analyses de la croissance tumorale, de l’histologie (prolifération, apoptose et vascularisation) et des analyses protéiques ont été menées en parallèle. De cette dernière étude, un marqueur particulier la E cadhérine, a été mis en évidence comme témoin indirect d’agressivité. En effet, au sein des tumeurs obtenues à partir de F1 HCT116, fraction himiosensible, l’expression de la E cadhérine est augmentée contrairement aux tumeurs obtenues à partir de F3 WiDr, fraction chimiorésistante, montrant une diminution d’expression de la E cadhérine.Ainsi, dans une troisième partie, sachant qu’un lien entre cellules initiant le cancer et E cadhérine a été mis en évidence, nous nous sommes focalisés sur son expression. Nous avons alors étudié son expression in vitro sur des cellules résistantes au 5 Fluorouracile. Puis, son expression a été étudiée ex vivo au sein de tissus et de sérums de patients opérés de cancer colorectal.The ColoRectal Cancer (CCR) is the second leading cause of cancer mortality in the world. The risk of recurrence after curative treatment reaches 45% for stages 3. One of the hypotheses currently able to explain the metastatic process and the recurrences is the presence within it of "stem" cells, which can "initiate" the cancer. Our reflection is in line with the work carried out in our Laboratory, entitled "Strategies for the isolation and characterization of cells that initiate colorectal cancer" (Mélin et al, 2012).In the first part, our work focused on in vitro analysis of the sensitivity of fractions enriched in CIC to different chemotherapy molecules most commonly used in colorectal cancer (CRC). Then, in a second part, the analysis of the tumors obtained after transplantation was made ex ovo on Chicken Embryo Chorio-Allantoid Membrane (CAM), an easily manipulated model, inexpensive and very fast. This model provides information on the key phenomena of tumorigenesis and neoangiogenesis. Analyzes of tumor growth, histology (proliferation, apoptosis and vascularization) and protein analyzes were carried out in parallel. From this last study, a particular marker, E cadherin, was highlighted as an indirect link with witness of aggressiveness. Indeed, within the tumors obtained from F1 HCT116, the chemosensitive fraction, the expression of cadherin E was increased in contrast to the tumors obtained from F3 WiDr, chemoresistant fraction, showing a decrease in expression of E cadherin.Thus, in a third part, knowing that a link between cells initiating cancer and E cadherin was highlighted, we focused on its expression. We first studied its expression in vitro on 5 Fluorouracilresistant cells. Its expression was then studied ex vivo in tissues and sera of operated patients of CRC

Circulating Tumour Cells as Prognostic Biomarkers in Colorectal Cancer: A Systematic Review.

Despite therapeutic advances, colorectal cancer (CRC) is still one of the deadliest cancers, partly due to local recurrence and metastatic disease. Tumour cells that spread by gaining access to peripheral blood are called circulating tumour cells (CTCs). These may be present before there are any clinical signs, but can be detected within blood samples. CTCs from patients with CRC may be isolated in a laboratory for characterization and multiple analyses. In this review, we focus on the prognostic potential of CTCs detection, by evaluating the reported progress and applications of such analyses. Our search found 77 relevant studies that reported CTC detection in CRC. Both cell count and features were reported as promising prognosis biomarkers. Since CTCs are rare and can lose their differentiation, new tools are being developed to improve detection. CTCs may have potential as prognostic biomarkers for CRC in terms of survival prediction, anticipating chemotherapy resistance, and surgical planning. CTCs are not yet used in clinical practice, and further investigations are required in order to better frame their practical value

The Role of Cancer Stem Cells in Colorectal Cancer: From the Basics to Novel Clinical Trials

The treatment options available for colorectal cancer (CRC) have increased over the years and have significantly improved the overall survival of CRC patients. However, the response rate for CRC patients with metastatic disease remains low and decreases with subsequent lines of therapy. The clinical management of patients with metastatic CRC (mCRC) presents a unique challenge in balancing the benefits and harms while considering disease progression, treatment-related toxicities, drug resistance and the patient’s overall quality of life. Despite the initial success of therapy, the development of drug resistance can lead to therapy failure and relapse in cancer patients, which can be attributed to the cancer stem cells (CSCs). Thus, colorectal CSCs (CCSCs) contribute to therapy resistance but also to tumor initiation and metastasis development, making them attractive potential targets for the treatment of CRC. This review presents the available CCSC isolation methods, the clinical relevance of these CCSCs, the mechanisms of drug resistance associated with CCSCs and the ongoing clinical trials targeting these CCSCs. Novel therapeutic strategies are needed to effectively eradicate both tumor growth and metastasis, while taking into account the tumor microenvironment (TME) which plays a key role in tumor cell plasticity

The Effect of Metformin on the Survival of Colorectal Cancer Patients with Type 2 Diabetes Mellitus

International audienceIntroduction: Colorectal cancer (CRC) is the second most deadly cancer worldwide and the third most diagnosed globally. Evidence from previous studies suggests a protective effect of metformin in patients with CRC. The aim of this study was to examine the associations between metformin use and overall survival (OS) and disease-free survival (DFS) in CRC patients with type 2 diabetes mellitus.Method: This was a historical cohort study. It included diabetic patients who underwent surgery for CRC at Limoges’ University Hospital between 2005 and 2019. Data on the characteristics of patients, CRC, comorbidities and drug exposure were collected from the patients’ electronic medical records. The exposure was the use of metformin. Patients were followed for two years after surgery. The outcomes were overall survival (OS) and disease-free survival (DFS). Multivariate analysis using the Cox model was performed and all statistical analyses were done with IBM SPSS Statistics 22.Results: Of the 1605 patients operated for CRC, 290 patients were identified with type 2 diabetes mellitus. Half of the diabetic patients were treated with metformin (49.7%).The 2-year OS rate for metformin users was 86.9±2.9% and 71.0±4.0% for metformin non-users (p=0.001). The Cox regression model showed a 64.0% reduction in all-cause mortality (adjusted hazard ratios (aHR), 0.36; 95% confidence interval 95%CI 0.17-0.73) among metformin users compared with non-users. Furthermore, metformin users had better DFS than non-users (aHR, 0.31; 95%CI 0.19-0.52).Conclusion: The use of metformin may improve OS and DFS in diabetic patients with CRC. Further prospective studies are also recommended to better explore the effect of this drug

Liquid Biopsy as a Prognostic and Theranostic Tool for the Management of Pancreatic Ductal Adenocarcinoma.

Pancreatic ductal adenocarcinomas (PDAC) represent one of the deadliest cancers worldwide. Survival is still low due to diagnosis at an advanced stage and resistance to treatment. Herein, we review the main types of liquid biopsy able to help in both prognosis and adaptation of treatments