How well do we measure the impact of bowel dysfunction on health-related quality of life after rectal cancer surgery?

BACKGROUND: Rectal cancer surgery risks causing bowel dysfunction, which has an important impact on health-related quality of life. The validity of generic tools used to measure health-related quality of life after bowel dysfunction is unclear. This study aims to determine the content validity of health-related quality-of-life measurement tools in rectal cancer. METHODS: This was a qualitative single-center study in which adult patients who underwent rectal cancer surgery with sphincter preservation from July 2017 to October 2020 were recruited. Patients were excluded if they developed local metastasis, required a permanent stoma, or had surgery <1 year since recruitment. Telephone-based semi-structured interviews were conducted. Bowel dysfunction was measured using the Low Anterior Resection Syndrome score. Content analysis was achieved using the International Classification of Functioning framework. RESULTS: Recurrent bowel dysfunction-related concepts included "Mental functions," "Defecation functions," "Emotional functions," "Recreation and leisure," "Intimate relationships," and "Remunerative employment." A mean of 7.5 recurrent bowel dysfunction-related concepts were identified within the health-related quality of life instruments analyzed. The European Organization for Research and Treatment of Cancer Quality-of-Life Questionnaire-C30 (n = 11) and the 36-Item Short Form Health Survey (n = 9) covered the greatest number of recurrent bowel dysfunction-related concepts. Concepts such as "Mental functions," "Urination functions," "Sexual functions," "Driving," and "Mobility" were not covered by any instrument. CONCLUSION: The content of traditional health-related quality-of-life instruments is missing important areas that represent the impact of bowel dysfunction after rectal cancer surgery on health-related quality of life. These findings could help improve patient-centered care in rectal cancer surgery.

The impact of restorative proctectomy versus permanent colostomy on health-related quality of life after rectal cancer surgery using the patient-generated index.

BACKGROUND: The impact of bowel dysfunction versus colostomy on quality of life after rectal cancer surgery is poorly understood. BACKGROUND: To evaluate the quality of life after rectal cancer surgery in patients with colostomy versus restorative proctectomy. METHODS: A mixed-methods study measuring quality of life using the Patient-Generated Index, patients were asked to list up to 5 areas of their life affected by their surgery. Areas were then weighted according to patients' preferences for improvement to generate a score from 0-100. The areas reported by patients were linked to the International Classification of Functioning for content analysis. Bowel dysfunction was measured using the low anterior resection syndrome score, and patients were then grouped according to (1) colostomy, (2) no/minor, or (3) major low anterior resection syndrome. Quality of life was compared between groups. RESULTS: Overall, 121 patients were included (colostomy n = 39, restorative proctectomy n = 82). There were no differences in demographics, neoadjuvant radiotherapy, or time to follow-up between groups. In the restorative proctectomy group, 53% had no/minor, and 47% had major low anterior resection syndrome. Overall, patients with colostomy had significantly lower quality-of-life scores than those with restorative proctectomy. However, patients with major low anterior resection syndrome scored similarly to those with colostomy. On content analysis, patients with colostomies reported more problems with sexual function, body image, and sports. Patients with restorative proctectomy reported more problems with sleep, using transportation, and taking care of themselves. CONCLUSION: Colostomy has a more detrimental impact on quality of life than restorative proctectomy. However, bowel dysfunction severity is important to consider. The patient experience between treatments differs.

Understanding the Impact of Bowel Dysfunction on Quality of Life After Rectal Cancer Surgery From the Patient's Perspective.

BACKGROUND: Bowel dysfunction is an important consequence of rectal cancer surgery' and the specific quality-of-life domains that are affected remain unclear and unaddressed by generic surveys. OBJECTIVE: This study aimed to identify quality-of-life domains most affected by rectal cancer surgery. DESIGN: Qualitative content analysis. SETTINGS: Semistructured interviews conducted by telephone with patients recruited from a single university-affiliated colorectal referral center. PATIENTS: Adult patients were included if they underwent rectal cancer surgery with sphincter preservation from July 2017 to July 2020. Patients were excluded if their surgery was <1 year since the recruitment date, received a permanent stoma, or developed recurrence or metastasis. MAIN OUTCOME MEASURES: Bowel dysfunction was evaluated via the low anterior resection syndrome score. Interview transcripts were coded by 2 independent reviewers and evaluated for concordance. Qualitative content analysis was used to identify themes, and their frequency of occurrence was quantified (percent total number of interviews). RESULTS: A total of 54 patient interviews were conducted. Analysis revealed 5 quality-of-life-related themes impacted by bowel dysfunction: experiencing psychological and emotional stress, challenging roles and relationships within society, encountering physical limitations, restricting leisure and recreational activities, and learning self-empowerment and adapting to change. Patients with minor and major bowel dysfunction were more likely to report disruption to their social activities and their role as a sexual partner versus those with no bowel dysfunction. Patients with major bowel dysfunction were more likely to report effects on sleep versus those with no and minor bowel dysfunction. LIMITATIONS: Single center, self-reported, and observer bias. CONCLUSION: The impact of bowel dysfunction on quality of life includes a wide range of themes that extend beyond traditional measures. These results may help better inform patients in the preoperative setting and serve as a basis for the development of a more patient-centered quality-of-life survey. COMPRENDER EL IMPACTO DE LA DISFUNCIN INTESTINAL EN LA CALIDAD DE VIDA DESPUS DE LA CIRUGA DE CNCER DE RECTO DESDE LA PERSPECTIVA DEL PACIENTE: ANTECEDENTES:La disfunción intestinal es una consecuencia importante de la cirugía del cáncer de recto y los dominios específicos de la calidad de vida que se ven afectados siguen sin estar claros y sin abordarse en las encuestas genéricas.OBJETIVO:Identificar los dominios de calidad de vida más afectados por la cirugía del cáncer de recto.DISEÑO:Análisis cualitativo de contenido.ÁMBITOS:Entrevistas semiestructuradas realizadas por teléfono con pacientes reclutados de un único centro de referencia colorrectal afiliado a una universidad.PACIENTES:Pacientes adultos intervenidos de cáncer de recto con preservación de esfínter del 07/2017 al 07/2020. Los pacientes fueron excluidos si su cirugía fue <1 año desde la fecha de reclutamiento, recibieron un estoma permanente o desarrollaron recurrencia o metástasis.PRINCIPALES MEDIDAS DE RESULTADO:La disfunción intestinal se evaluó a través de la puntuación del síndrome de resección anterior baja. Dos revisores independientes codificaron las transcripciones de las entrevistas y evaluaron su concordancia. Se utilizó el análisis de contenido cualitativo para identificar los temas, cuantificando su frecuencia de aparición (porcentaje del número total de entrevistas).RESULTADOS:Se realizaron un total de 54 entrevistas a pacientes. El análisis reveló cinco temas relacionados con la calidad de vida afectados por la disfunción intestinal: experimentar estrés psicológico y emocional, roles y relaciones desafiantes dentro de la sociedad, encontrar limitaciones físicas, restringir actividades recreativas y de ocio, y autoempoderamiento y adaptación al cambio. Los pacientes con disfunción intestinal menor y mayor tenían más probabilidades de informar la interrupción de las actividades sociales y el papel como pareja sexual en comparación con aquellos sin disfunción intestinal. Los pacientes con disfunción intestinal importante tenían más probabilidades de informar efectos sobre el sueño en comparación con aquellos sin disfunción intestinal o con disfunción intestinal menor.LIMITACIONES:Sesgo de un solo centro, autoinformado y observador.CONCLUSIÓN:El impacto de la disfunción intestinal en la calidad de vida incluye una amplia gama de temas que se extienden más allá de las medidas tradicionales. Estos resultados pueden ayudar a informar mejor a los pacientes en el entorno preoperatorio y servir como base para el desarrollo de una encuesta de calidad de vida más centrada en el paciente. (Traducción-Dr. Yesenia Rojas-Khalil ).

Activation of Wnt signaling by amniotic fluid stem cell-derived extracellular vesicles attenuates intestinal injury in experimental necrotizing enterocolitis.

Necrotizing enterocolitis (NEC) is a devastating intestinal disease primarily affecting preterm neonates and causing high morbidity, high mortality, and huge costs for the family and society. The treatment and the outcome of the disease have not changed in recent decades. Emerging evidence has shown that stimulating the Wnt/ß-catenin pathway and enhancing intestinal regeneration are beneficial in experimental NEC, and that they could potentially be used as a novel treatment. Amniotic fluid stem cells (AFSC) and AFSC-derived extracellular vesicles (EV) can be used to improve intestinal injury in experimental NEC. However, the mechanisms by which they affect the Wnt/ß-catenin pathway and intestinal regeneration are unknown. In our current study, we demonstrated that AFSC and EV attenuate NEC intestinal injury by activating the Wnt signaling pathway. AFSC and EV stimulate intestinal recovery from NEC by increasing cellular proliferation, reducing inflammation and ultimately regenerating a normal intestinal epithelium. EV administration has a rescuing effect on intestinal injury when given during NEC induction; however, it failed to prevent injury when given prior to NEC induction. AFSC-derived EV administration is thus a potential emergent novel treatment strategy for NEC.

Essential Role of Syntaxin-Binding Protein-1 in the Regulation of Glucagon-Like Peptide-1 Secretion.

Circadian secretion of the incretin, glucagon-like peptide-1 (GLP-1), correlates with expression of the core clock gene, Bmal1, in the intestinal L-cell. Several SNARE proteins known to be circadian in pancreatic α- and ß-cells are also necessary for GLP-1 secretion. However, the role of the accessory SNARE, Syntaxin binding protein-1 (Stxbp1; also known as Munc18-1) in the L-cell is unknown. The aim of this study was to determine whether Stxbp1 is under circadian regulation in the L-cell and its role in the control of GLP-1 secretion. Stxbp1 was highly-enriched in L-cells, and STXBP1 was expressed in a subpopulation of L-cells in mouse and human intestinal sections. Stxbp1 transcripts and protein displayed circadian patterns in mGLUTag L-cells line, while chromatin-immunoprecipitation revealed increased interaction between BMAL1 and Stxbp1 at the peak time-point of the circadian pattern. STXBP1 recruitment to the cytosol and plasma membrane within 30 minutes of L-cell stimulation was also observed at this time-point. Loss of Stxbp1 in vitro and in vivo led to reduced stimulated GLP-1 secretion at the peak time-point of circadian release, and impaired GLP-1 secretion ex vivo. In conclusion, Stxbp1 is a circadian regulated exocytotic protein in the intestinal L-cell that is an essential regulatory component of GLP-1 secretion.

Insulin-like growth factor-binding protein-4 inhibits epithelial growth and proliferation in the rodent intestine.

Insulin-like growth factor-binding protein-4 (IGFBP-4) is a binding protein that modulates the action of insulin-like growth factor-1 (IGF-1), a growth factor whose presence is required for the intestinotrophic effects of glucagon-like peptide-2 (GLP-2). GLP-2 is a gut hormone that uses both IGF-1 and epidermal growth factor (EGF) as intermediary factors to promote intestinal growth. Therefore, to elucidate the mechanism through which IGFBP-4 regulates IGF-1 activity in the intestine, proliferation assays were conducted using rat intestinal epithelial cells (IEC-6). IGF-1 and EGF synergistically enhanced proliferation, an effect that was dose-dependently decreased by IGFBP-4 ( P < 0.05-0.001) in an IGF-1 receptor (R)- and MEK1/2- but not a phosphatidylinositol 3-kinase-dependent manner ( P > 0.05 for IGFBP-4 effects with IGF-1R and MEK1/2 inhibitors). Intestinal organoids derived from IGFBP-4 knockout mice demonstrated significantly greater Ki-67 expression and an enhanced surface area increase in response to IGF-1 treatment, compared with organoids from control mice ( P < 0.05-0.01). GLP-2 is also known to increase the mucosal expression of IGFBP-4 mRNA. To investigate whether this occurs through the actions of its intermediaries, IGF-1 and EGF, inducible intestinal epithelial-IGF-1R knockout and control mice were treated for 10 days with and without the pan-ErbB inhibitor, CI-1033. However, no differences in mucosal IGFBP-4 mRNA expression were found for any of the treatment groups ( P > 0.05). Consistently, IEC-6 cells treated with IGF-1 and/or EGF displayed no alteration in IGFBP-4 mRNA or in cellular and secreted IGFBP-4 protein ( P > 0.05). Overall, this study establishes that endogenous IGFBP-4 plays an important role in inhibiting IGF-1-induced intestinal epithelial proliferation and that mucosal IGFBP-4 expression is independent of IGF-1 and EGF. NEW & NOTEWORTHY This study demonstrates, for the first time, the inhibitory role of locally expressed insulin-like growth factor-binding protein-4 (IGFBP-4) on the intestinal proliferative actions of IGF-1 and supports the notion of the synergistic roles of IGF-1 and EGF in promoting intestinal epithelial growth. In turn, intestinal IGFBP-4 expression was not found to be regulated by IGF-1 and/or EGF.