High Resolution Colon Manometry in patients suffering from LARS after low anterior resection for rectal cancer
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ABSTRACT:
DISEASE(S): Rectal Cancer, Low Anterior Resection Syndrome, Lars, Fecal Incontinence, Fecal Urgency, Frequency, Fragmented Defecation, Soiling, Bowel Symptoms
PROVIDER: 2442274 | ecrin-mdr-crc |
REPOSITORIES: ECRIN MDR
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Project description:In this study, we identify leucyl-tRNA synthetase (LARS) as a breast tumor suppressor. To identify the mechanism underlying LARS-mediated breast tumor suppression, we first conducted charged tRNA profiling to assess charged and total tRNA-Leu expression in cell lines with high and low LARS expression. Expression of select charged and total tRNA-Leu isoacceptors were reduced in cell lines with lower LARS expression. We then conducted RNA-Seq and translation profiling including ribosome profiling (Ribo-Seq), polysome profiling in LARS-depleted cell lines. To test our hypothesis in vivo, we also performed RNA-Seq of ribosome-associated RNAs in Lars depleted PyMT tumors within RiboTag mice. The analyses implicate LARS as a regulator of leucine-rich translation.
2022-01-05 | GSE176130 | GEO
Project description:Oncological rectal cancer outcomes have improved considerably because of optimal surgery by total mesorectal excision in conjunction with multidisciplinary team management by selective multimodal therapy (ie, neo-adjuvant chemo-radiotherapy). The 5-year survival has increased to more than 50% and local recurrence has been reduced to less than 10%. These advancements have resulted in more patient receiving sphincter-preserving surgery (SPS). With an increasing number of rectal cancer survivors, the investigators observe a rising attention to the disordered bowel function after SPS, called "low anterior resection syndrome" (LARS). LARS appear immediately after surgery, becoming most pronounced during the first few months, and improved thereafter, reaching a steady state after around two years. However, up to 60% of patients with SPS suffer from LARS which impaired their quality of life (QoL). The prevalence and severity of LARS is difficult to assess due to heterogeneity of the assessment tools. A group of Danish authors have recently developed and validated a five-item instruments for evaluation of LARS (LARS score). It represents to date the best questionnaire to capture anorectal postoperative function and consists of five items: incontinence for flatus, incontinence for liquid stool, frequency of bowel movements, clustering of stools, and urgency. It allows a categorization of patients into 3 groups: no LARS (0-20 points), minor LARS (21-29 points), and major LARS (30-42 points). Developed in Danish, it is now internationally validated with translations in Chinese, English, German, Spanish and Swedish. To our knowledge, French version of the LARS score is not yet available. The aim of our study will be to adapt the LARS scale questionnaire to the French language (LARS-F), and assess its psychometric properties.
Inclusion criteria will be patients 18 years old or above who were operated for rectal cancer from 2007 to 2015. Exclusion criteria will include the presence of stoma and/or known disseminated or recurrent disease. Patients will be identified through local databases by the local investigators at each of the participating centers with a minimum duration of 24 months after surgery to allow their bowel function to have regained stability. This study will be supported by the French Research Group of Rectal Cancer Surgery in order to allow the feasibility of the project.
After translation/back-translation procedures in accordance with the permission from the original authors, the LARS-F score and the whole translation process will be then sent to the original authors for approval. Then a pilot study will be conducted. The French questionnaire (LARS-F score) will be then administered to 100 patients in order to verify the adequacy and degree of comprehension of the questions. Reproducibility will be investigated by a test-retest procedure. A randomly selected subgroup of participants (n= 400) will be sent the LARS-F score questionnaire twice (with an interval of two weeks). The test-retest reliability of the questionnaire will be assessed by the Cohen’s Kappa (no, minor and major LARS scores) or by intra-class correlation coefficient, ICC (quantitative LARS score). Then, eligible patients will receive a postal invitation to complete the LARS-F score and the l’European Organization for Research and treatment of Cancer (EORTC) QLQ-C30 and QLQ-CR29, respectively. The validity of the LARS-F score will be tested by using the indicators of convergent validity and discriminant validity. The convergent validity will be determined notably in this study by computing the correlations between the LARS-F score and the EORTC QLQ-C30 and QLQ-CR29 domains. For discriminant validity testing, the investigators will use known variables to affect bowel function after SPS, such as gender, age, neo-adjuvant radiation therapy, distance of the tumor from the anal verge, prior temporary stoma, and length of postoperative period.
The validation of the French version of the LARS score will allow to use a scientific instrument in order to assess both prevalence and severity of LARS. This instrument will allow to develop a future research and clinical practice in France. It will be used in the daily clinical practice to identify patients with LARS score. It will hopefully lead to improve the awareness of clinicians, in order to improve the prevention and the treatment of bowel dysfunction, as well as the information given to patients. In the future, the investigators will able to develop a new patient-led follow-up program based on symptom burden and health-related QoL.
| 2276331 | ecrin-mdr-crc
Project description:In the past decade, colorectal cancer management improved considerably with total mesorectal excision as well as the multidisciplinary management relying on neoadjuvant radiochemotherapy. This forward leap is currently responsible for an increase in the survivorship of colorectal cancer patients to more than 50% at 5 years. Additively the surgical approach is now more inclined towards sphincter preserving procedures, which allows the conservation of body image but can have negative bowel function repercussions consisting of urgency and incontinence ; all these terms encompassed in the low anterior resection syndrome.
In the light of these findings many studies developed assessment tools in order to objectively measure this functional alteration among which are the low anterior resection syndrome questionnaire (LARS) and the WEXNER score. These tools designed to assess bowel function after sphincter-preserving surgery are now translated and validated into various languages and used in different countries.
The LARS score relies on the frequency of the symptoms and allows the categorization of patients into 3 groups: no LARS (0-20 points), minor LARS (21-29 points), and major LARS (30-42 points). It assesses the frequency of emptying, incontinence ( liquid, gas ), and other symptoms such as urgency and incomplete voiding. On the other hand, the WEXNER score relies on the examination of the frequency of three types of fecal incontinence (solid, liquid, and gas) and their consequences (pad wearing and lifestyle alteration) with frequency options ranging from never (score 0) through to always (meaning at least once per day; score 4). The score ranges from 0 (perfect continence) to 20 (complete incontinence).
The aim of our study is to adapt and validate the LARS and WEXNER score to the moroccan arabic dialect.
| 2319282 | ecrin-mdr-crc
Project description:Interventions: Electroacupuncture exposure group:NA;None electroacupuncture exposure group:NA
Primary outcome(s): Proportion of patients with reduced defecation dysfunction as judged by LARS scale score;Proportion of reductions from baseline in the average number of bowel movements per day
Study Design: Cohort study
| 114147 | ecrin-mdr-crc
Project description:IntroductionLow anterior resection (LAR) for rectal cancer affects bowel function after the operation, causing a group of symptoms known as LAR Syndrome (LARS). LARS score is a patient-reported questionnaire to assess bowel dysfunction after the LAR operation. This study performed to validate the Persian (Farsi) translation of the LARS score and to investigate the psychometric properties of the score. The impact of LARS on the Quality of Life (QoL) of patients was also assessed.Materials and methodsThe LARS score was translated into Persian. Participants with a history of rectal cancer and low anterior resection were asked to complete the LARS score questionnaire. They were also asked a single question evaluating the impact of bowel function on QoL. Discriminative validity, convergent validity, sensitivity, and specificity of the questionnaire were calculated. A group of patients completed the score twice to assess the reliability of the questionnaire.ResultsFrom 358 patients with rectal cancer, 101 participants completed the Persian questionnaire. Answers of a high fraction of participants showed a moderate/perfect fit between their LARS score and their QoL. The Persian score demonstrated good convergent validity. It was able to differentiate between participants in terms of gender and T staging of the primary tumor. The score had high reliability.ConclusionThe Persian translation of the LARS score has excellent psychometric properties compared to previous translations in other languages. Therefore, it is a valid and reliable questionnaire to assess LARS.
| S-EPMC7906462 | biostudies-literature
Project description:IntroductionMany bowel problems following low anterior resection (LAR) for rectal cancer considerably impair the quality of life (QoL) of patients. The LAR syndrome (LARS) scale is a self-report questionnaire to identify and assess bowel dysfunction after rectal cancer surgery. It has been translated and validated in several languages but not in French (metropolitan French). The primary objective is to adapt the LARS scale to the French language (called French-LARS score) and to assess its psychometric properties. Secondary objectives are to assess both the prevalence and severity of LARS and to measure their impact on QoL.Methods and analysisA French multicentre observational cohort study has been designed. The validation study will include translation of the LARS scale following the current international recommendations, assessment of its reliability, convergent and discriminant validities, sensitivity, internal consistency, internal validity and confirmatory analyses. One thousand patients will be enrolled for the analyses. The questionnaire will be initially administered to the first 100 patients to verify the adequacy and degree of comprehension of the questions. Then reproducibility will be investigated by a test-retest procedure in the following 400 patients.An analysis will be conducted to determine the correlation between the LARS score and the Quality of Life Questionnaire (QLQ; European Organization for Treatment and Research of Cancer's QLQ-C30, QLQ-CR29). Risk factors linked to QoL deterioration will be identified and their impact will be measured. This study will meet the need for a validated tool to improve patient care and QoL.Ethics and disseminationThe institutional review board of the University Hospital of Caen and the ethics committee (CPP Nord Ouest I, 25 January 2019) approved the study.Trial registration numberNCT03569488.
| S-EPMC7064062 | biostudies-literature
Project description:Leucine-induced Regulatory LARS B cells Contribute to Colorectal Cancer Immunoevasion
| PRJNA762263 | ENA
Project description:Primary outcome(s): The correlation between the LARS score and conventional faecal incontinence scores, and quality of life scores.
| 2650340 | ecrin-mdr-crc
Project description:Data assessing the long-term bowel dysfunction following low anterior resection is still lacking. The aim of this study is to evaluate late functional results of patients who underwent rectal resection for rectal cancer. This included calculating LARS and Wexner score and identifying possible risk factors of late postoperative bowel disorders.
| 2303269 | ecrin-mdr-crc
Project description:Double-blind, randomized, placebo controlled phase 2 study to explore the efficacy and safety of HEM1036 in the treatment of subjects with LARS
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