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1.
EXCLI J ; 22: 862-866, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37780938

RESUMEN

Dieulafoy's lesion is a life-threatening and rare vascular malformation of the submucosal vessel that protrudes to the mucosa of the gastrointestinal tract. The vessel is abnormally dilated, and if it ruptures, it can cause severe acute gastrointestinal bleeding. We report an upper GI bleeding case due to Dieulafoy's lesion in the gastric fundus of the stomach in a 76-year-old female. The patient presented with hematemesis and melena associated with anemia. An esophagogastroduodenoscopy (OGD) was performed which showed profuse pulsatile bleeding at the gastric fundus. Following that, gastrotomy confirmed the diagnosis of Dieulafoy's lesion. Endoscopy is the main diagnostic and therapeutic tool for Dieulafoy's lesion. Endoscopic treatment includes injective, ablative and mechanical therapies. The majority of cases are treated endoscopically, while in some cases, surgical intervention is deemed to be necessary as it is currently the only definitive treatment of Dieulafoy's lesion.

2.
Ann Surg ; 278(5): 642-646, 2023 11 01.
Artículo en Inglés | MEDLINE | ID: mdl-37796749

RESUMEN

This paper summarizes the proceedings of the joint European Surgical Association ESA/American Surgical Association symposium on Surgical Education that took place in Bordeaux, France, as part of the celebrations for 30 years of ESA scientific meetings. Three presentations on the use of quantitative metrics to understand technical decisions, coaching during training and beyond, and entrustable professional activities were presented by American Surgical Association members and discussed by ESA members in a symposium attended by members of both associations.


Asunto(s)
Tutoría , Humanos , Estados Unidos , Escolaridad , Francia
3.
Ann Surg ; 278(5): 655-661, 2023 11 01.
Artículo en Inglés | MEDLINE | ID: mdl-37465982

RESUMEN

INTRODUCTION: Over the past 2 decades, physicians' wellbeing has become a topic of interest. It is currently unclear what the current needs are of early career academic surgeons (ECAS). METHODS: Consensus statements on academic needs were developed during a Delphi process, including all presenters from the previous European Surgical Association (ESA) meetings (2018-2022). The Delphi involved (1) a literature review, (2) Delphi form generation, and (3) an accelerated Delphi process. The Delphi form was generated by a steering group that discussed findings identified within the literature. The modified accelerated e-consensus approach included 3 rounds over a 4-week period. Consensus was defined as >80% agreement in any round. RESULTS: Forty respondents completed all 3 rounds of the Delphi. Median age was 37 years (interquartile range 5), and 53% were female. Majority were consultant/attending (52.5%), followed by PhD (22.5%), fellowship (15%), and residency (10%). ECAS was defined as a surgeon in 'development' years of clinical and academic practice relative to their career goals (87.9% agreement). Access to split academic and clinical contracts is desirable (87.5%). Consensus on the factors contributing to ECAS underperformance included: burnout (94.6%), lack of funding (80%), lack of mentorship (80%), and excessive clinical commitments (80%). Desirable factors to support ECAS development included: access to e-learning (90.9%), face-to-face networking opportunities (95%), support for research team development (100%), and specific formal mentorship (93.9%). CONCLUSION: The evolving role and responsibilities of ECAS require increasing strategic support, mentorship, and guidance on structured career planning. This will facilitate workforce sustainability in academic surgery in the future.


Asunto(s)
Internado y Residencia , Cirujanos , Humanos , Femenino , Adulto , Masculino , Evaluación de Necesidades , Consenso , Técnica Delphi
4.
Cureus ; 15(5): e39088, 2023 May.
Artículo en Inglés | MEDLINE | ID: mdl-37332466

RESUMEN

For individuals suffering from severe refractory ulcerative colitis (UC) who are unresponsive to medical treatment, a total proctocolectomy and ileal pouch-anal anastomosis (IPAA) surgery is the gold-standard treatment. However, its complications include anastomotic leaks, pelvic or perianal abscesses, and rare complications such as pouch volvulus. To our knowledge, there is a scarcity of case reports on patients with, specifically, a recurrent pouch volvulus. We present a case of a 57-year-old female with refractory UC who had undergone this treatment with no initial complications; 15 years later, she presented with intermittent bouts of obstruction. An exploratory laparotomy was performed; however, no adhesions or necrosis were found. Following investigations, pouch volvulus was confirmed. She subsequently underwent four endoscopic decompressions in the same year and ultimately received an enteropexy of the pouch. The volvulus reoccurred and, ultimately, the decision was made to perform a loop ileostomy. The patient, to date, is alive and doing well with her permanent ileostomy.

5.
Dis Colon Rectum ; 65(12): 1415-1417, 2022 12 01.
Artículo en Inglés | MEDLINE | ID: mdl-36102875
6.
Ann Surg ; 276(5): 743-745, 2022 11 01.
Artículo en Inglés | MEDLINE | ID: mdl-35861354
7.
Dis Colon Rectum ; 65(2): 284-294, 2022 02 01.
Artículo en Inglés | MEDLINE | ID: mdl-34990427

RESUMEN

BACKGROUND: Changes in anorectal sensation have been reported in patients with fecal incontinence, and there is limited evidence that sacral nerve stimulation can restore normal sensation. OBJECTIVE: The aims of the present study were to investigate changes in the transmission of sensory anorectal stimuli in a rodent model of fecal incontinence and to study the effects of sacral nerve stimulation on defecation behavior. DESIGN: An established model of fecal incontinence was utilized for this study. INTERVENTION: Pudendal nerve stretch and compression were used in 16 adult female Wistar rats and were monitored for 3 weeks: 6 rats received sacral nerve stimulation for 1 week by using an implantable neurostimulator and 10 rats had nonfunctioning "dummy" devices inserted. Five additional rats were sham operated. Anorectal cortical evoked potentials were used as a surrogate marker for anorectal sensory function. MAIN OUTCOME MEASURES: The primary outcomes measured were fecal incontinence index, evoked potential amplitude, and latency. RESULTS: Fifty percent of rats showed behavioral signs of fecal incontinence measured by the Fecal Incontinence Index (>0.20), calculated by using the pellet distribution outside the cage's latrine area. Anorectal evoked potential amplitude was reduced in rats with a Fecal Incontinence Index >0.20 (p = 0.019). The amplitude of forepaw evoked potentials recorded as a control was not different between groups. Chronic sacral nerve stimulation using the fully implantable device and custom rodent lead was safe and stable during this chronic prospective study. Incontinent rats (n = 3) that received sacral nerve stimulation showed an improvement of Fecal Incontinence Index and an increase of evoked potential amplitude to anorectal stimulation compared with the dummy implant controls (n = 5). LIMITATIONS: The main limitation is the small number of animals that received sacral nerve stimulation. CONCLUSIONS: Chronic sacral nerve stimulation is feasible in rats when miniature telemetric devices are used. Behavioral signs of fecal incontinence were positively correlated with the latency of anorectal evoked potentials. See Video Abstract at http://links.lww.com/DCR/B712.RELACIÓN ENTRE LA ACTIVACIÓN CORTICAL EN RESPUESTA A LOS ESTÍMULOS ANORRECTALES Y EL COMPORTAMIENTO DE CONTINENCIA EN RATAS QUE SE COMPORTAN LIBREMENTE ANTES Y DESPUÉS DE LA APLICACIÓN DE ESTIMULACIÓN DEL NERVIO SACRO. ANTECEDENTES: Se han informado cambios en la sensación anorrectal en pacientes con incontinencia fecal y hay evidencia limitada de que la estimulación del nervio sacro puede restaurar la sensación normal. OBJETIVO: Los objetivos del presente estudio fueron investigar los cambios en la transmisión de estímulos anorrectales sensoriales en un modelo de roedor de incontinencia fecal y estudiar los efectos de la estimulación del nervio sacro en la conducta de defecación. DISEO: Un modelo establecido de incontinencia fecal. INTERVENCIN: Se utilizó estiramiento y compresión del nervio pudendo en 16 ratas Wistar hembras adultas y se les realizó un seguimiento durante 3 semanas: seis ratas recibieron estimulación del nervio sacro durante 1 semana utilizando un neuroestimulador implantable y diez ratas tuvieron insertados dispositivos "ficticios" no funcionantes. Se operaron simuladamente cinco ratas adicionales. Los potenciales evocados corticales anorrectales se utilizaron como marcador subrogado de la función sensorial anorrectal. PRINCIPALES MEDIDAS DE RESULTADO: Índice de incontinencia fecal, amplitud de potenciales evocados y latencia. RESULTADOS: El cincuenta por ciento de las ratas mostró signos de comportamiento de incontinencia fecal medidos por el Índice de incontinencia fecal (> 0.20), calculado utilizando la distribución de heces fuera del área de la letrina de la jaula. La amplitud del potencial evocado anorrectal se redujo en ratas con un índice de incontinencia fecal >0.20 (p = 0.019). La amplitud de los potenciales evocados de la pata delantera registrados como control no fue diferente entre los grupos. La estimulación crónica del nervio sacro utilizando un dispositivo totalmente implantable y un cable de roedor personalizado fue segura y estable durante este estudio prospectivo crónico. Las ratas con incontinencia (N = 3) que recibieron estimulación del nervio sacro mostraron una mejora del índice de incontinencia fecal y un aumento de la amplitud del potencial evocado a la estimulación anorrectal en comparación con los controles de implante ficticio (N = 5). LIMITACIONES: La principal limitación es el pequeño número de animales que recibieron estimulación del nervio sacro. CONCLUSIONES: La estimulación crónica del nervio sacro es factible en ratas cuando se utilizan dispositivos telemétricos en miniatura. Los signos conductuales de incontinencia fecal se correlacionaron positivamente con la latencia de los potenciales evocados anorrectales. Consulte Video Resumen en http://links.lww.com/DCR/B712. (Traducción-Dr. Jorge Silva Velazco).


Asunto(s)
Excitabilidad Cortical/fisiología , Terapia por Estimulación Eléctrica/instrumentación , Conducta Excretoria Animal/fisiología , Incontinencia Fecal/fisiopatología , Incontinencia Fecal/terapia , Nervios Espinales , Animales , Modelos Animales de Enfermedad , Incontinencia Fecal/psicología , Femenino , Neuroestimuladores Implantables , Ratas , Ratas Wistar
8.
Colorectal Dis ; 23(9): 2228-2285, 2021 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-34060715

RESUMEN

This is a comprehensive and rigorous review of currently available data on the use of mesh in the pelvis in colorectal surgery. This guideline outlines the limitations of available data and the challenges of interpretation, followed by best possible recommendations.


Asunto(s)
Cirugía Colorrectal , Procedimientos Quirúrgicos del Sistema Digestivo , Humanos , Pelvis/cirugía , Prótesis e Implantes , Mallas Quirúrgicas
9.
Sci Rep ; 11(1): 7262, 2021 03 31.
Artículo en Inglés | MEDLINE | ID: mdl-33790336

RESUMEN

Butyrate is the primary energy source for colonocytes and is essential for mucosal integrity and repair. Butyrate deficiency as a result of colonic dysbiosis is a putative factor in ulcerative colitis (UC). Commensal microbes are butyrogenic, while others may inhibit butyrate, through hydrogenotropic activity. The aim of this study was to quantify butyrogenic and hydrogenotropic species and determine their relationship with inflammation within the colonic mucus gel layer (MGL). Mucosal brushings were obtained from 20 healthy controls (HC), 20 patients with active colitis (AC) and 14 with quiescent colitis (QUC). Abundance of each species was determined by RT-PCR. Inflammatory scores were available for each patient. Statistical analyses were performed using Mann-Whitney-U and Kruskall-Wallis tests. Butyrogenic R. hominis was more abundant in health than UC (p < 0.005), prior to normalisation against total bacteria. Hydrogenotropic B. wadsworthia was reduced in AC compared to HC and QUC (p < 0.005). An inverse correlation existed between inflammation and R. hominis (ρ - 0.460, p < 0.005) and B. wadsworthia (ρ - 0.646, p < 0.005). Other hydrogenotropic species did not widely colonise the MGL. These data support a role for butyrogenic bacteria in UC. Butyrate deficiency in UC may be related to reduced microbial production, rather than inhibition by microbial by-products.


Asunto(s)
Bilophila/metabolismo , Clostridiales/metabolismo , Colitis Ulcerosa/microbiología , Colon/microbiología , Mucosa Intestinal/microbiología , Adulto , Anciano , Butiratos/metabolismo , Femenino , Humanos , Masculino , Persona de Mediana Edad
10.
Neurogastroenterol Motil ; 33(7): e14070, 2021 07.
Artículo en Inglés | MEDLINE | ID: mdl-33522079

RESUMEN

BACKGROUND: Chronic constipation is a prevalent disorder that affects quality of life of patients and consumes resources in healthcare systems worldwide. In clinical practice, it is still considered a challenge as clinicians frequently are unsure as to which treatments to use and when. Over a decade ago, a Neurogastroenterology and Motility journal supplement devoted to the investigation and management of constipation was published (Neurogastroenterol Motil 2009;21(Suppl 2):1). In October 2018, the 3rd London Masterclass, entitled "Contemporary management of constipation" was held. The faculty members of this symposium were invited to write two reviews to present a collective synthesis of talks presented and discussions held during this meeting. The first review addresses epidemiology, diagnosis, clinical associations, pathophysiology, and investigation. PURPOSE: The present is the second of these reviews, providing contemporary perspectives and clinical challenges regarding behavioral, conservative, medical, and surgical treatments for patients presenting with constipation. It includes a management algorithm to guide clinical practice.


Asunto(s)
Estreñimiento/terapia , Adulto , Técnicas de Apoyo para la Decisión , Femenino , Humanos , Masculino
11.
Int J Colorectal Dis ; 36(6): 1175-1180, 2021 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-33438108

RESUMEN

PURPOSE: To compare the current clinical scoring systems used to quantify the severity of symptoms of faecal incontinence (FI) to patients' subjective scoring of parameters of psychosocial well-being. METHODS: Patients referred to six European centres for investigation or treatment of symptoms of FI between June 2017 and September 2019 completed a questionnaire that captured patient demographics, incontinence symptoms using St. Mark's Incontinence score (SMIS) and ICIQ-B, psychological well-being (HADS, Hospital Anxiety and Depression Scale), and social interaction (a three-item loneliness scale). RESULTS: Three hundred eighteen patients completed questionnaires (62 men, mean age 58.7). Sixty percent of the respondents were aged under 65. Median SMIS was 15 (11-18), ICIQ-B bowel pattern was 8 (6-11) and bowel control was 17 (13-22), similar across all demographic groups; however, younger patients were more likely to experience symptoms of depression and anxiety (HADS score > 10, 65.2% of patients age < 65 vs 54.9% of those ages > = 65, p = 0.03) with lower quality of life (ICIQ-B QoL, median score 19 (14-23)) vs age > = 65 (16 (11-21) (p < 0.005)). On loneliness score 25.5% reported often feeling isolated from others. One of the most significant concerns by patients was the fear and embarrassment related to unpredictable episodes of incontinence. CONCLUSION: The SMIS remains a useful tool for quantifying incontinence symptoms but may underestimate the psychosocial morbidity associated with unpredictable episodes of incontinence. Interventions aimed at decreasing anxiety and to address feelings of disgust may be helpful for a significant number of patients requiring treatment for FI.


Asunto(s)
Incontinencia Fecal , Incontinencia Urinaria , Anciano , Ansiedad , Humanos , Masculino , Persona de Mediana Edad , Calidad de Vida , Índice de Severidad de la Enfermedad , Encuestas y Cuestionarios
12.
Neurogastroenterol Motil ; 32(1): e13679, 2020 01.
Artículo en Inglés | MEDLINE | ID: mdl-31407463

RESUMEN

BACKGROUND: This manuscript summarizes consensus reached by the International Anorectal Physiology Working Group (IAPWG) for the performance, terminology used, and interpretation of anorectal function testing including anorectal manometry (focused on high-resolution manometry), the rectal sensory test, and the balloon expulsion test. Based on these measurements, a classification system for disorders of anorectal function is proposed. METHODS: Twenty-nine working group members (clinicians/academics in the field of gastroenterology, coloproctology, and gastrointestinal physiology) were invited to six face-to-face and three remote meetings to derive consensus between 2014 and 2018. KEY RECOMMENDATIONS: The IAPWG protocol for the performance of anorectal function testing recommends a standardized sequence of maneuvers to test rectoanal reflexes, anal tone and contractility, rectoanal coordination, and rectal sensation. Major findings not seen in healthy controls defined by the classification are as follows: rectoanal areflexia, anal hypotension and hypocontractility, rectal hyposensitivity, and hypersensitivity. Minor and inconclusive findings that can be present in health and require additional information prior to diagnosis include anal hypertension and dyssynergia. CONCLUSIONS AND INFERENCES: This framework introduces the IAPWG protocol and the London classification for disorders of anorectal function based on objective physiological measurement. The use of a common language to describe results of diagnostic tests, standard operating procedures, and a consensus classification system is designed to bring much-needed standardization to these techniques.


Asunto(s)
Gastroenterología/normas , Enfermedades Intestinales/clasificación , Enfermedades Intestinales/diagnóstico , Canal Anal/fisiopatología , Humanos , Manometría/métodos
13.
Sci Rep ; 9(1): 15683, 2019 10 30.
Artículo en Inglés | MEDLINE | ID: mdl-31666581

RESUMEN

Akkermansia muciniphila utilises colonic mucin as its substrate. Abundance is reduced in ulcerative colitis (UC), as is the relative proportion of sulphated mucin in the mucus gel layer (MGL). It is unknown if these phenomena are related, however reduced sulphated mucins could contribute to reduced abundance, owing to a lack of substrate. The aim of this study was to quantify A. muciniphila within the MGL and to relate these findings with markers of inflammation and the relative proportion of sulphomucin present. Colonic biopsies and mucus brushings were obtained from 20 patients with active UC (AC), 14 with quiescent UC (QUC) and 20 healthy controls (HC). A. muciniphila abundance was determined by RT-PCR. High iron diamine alcian-blue staining was performed for histological analysis. Patients with AC had reduced abundance of A. muciniphila compared to HC and QUC. A positive association was found between A. muciniphila abundance and higher percentage of sulphated mucin (ρ 0.546, p = 0.000). Lower abundances of A. muciniphila correlated with higher inflammatory scores (ρ = 0.294 (p = 0.001)). This study confirms an inverse relationship between A. muciniphila and inflammation and a positive association between A. muciniphila abundance and percentage of sulfated mucin in the MGL.


Asunto(s)
Colitis Ulcerosa/microbiología , Inflamación/genética , Mucinas/metabolismo , Verrucomicrobia/metabolismo , Adolescente , Adulto , Akkermansia , Biopsia , Colitis Ulcerosa/metabolismo , Colitis Ulcerosa/patología , Colon/metabolismo , Colon/microbiología , Femenino , Voluntarios Sanos , Humanos , Inflamación/metabolismo , Inflamación/microbiología , Mucosa Intestinal/metabolismo , Mucosa Intestinal/microbiología , Intestinos/microbiología , Masculino , Persona de Mediana Edad , Mucinas/aislamiento & purificación , Moco/metabolismo , Moco/microbiología , Verrucomicrobia/patogenicidad , Adulto Joven
14.
Neurogastroenterol Motil ; 31(12): e13709, 2019 12.
Artículo en Inglés | MEDLINE | ID: mdl-31452314

RESUMEN

BACKGROUND: The rat has served usefully as a model for fecal incontinence and exploration of the mechanism of action of sacral neuromodulation. However, there is a gap in knowledge concerning representation(s) on the primary sensory cortex of this anatomical region. METHODS: Multi-electrode array (32 channels) and intrinsic optical signal (IOS) processing were used to map cortical activation sites following anorectal electrical stimulation in the rat. A simple method for expanding a 32-electrode array to a virtual 2700 array was refined. KEY RESULTS: The IOS method identified activation of parietal cortex following anorectal or first sacral nerve root (S1) stimulation; however, the signal was poorly localized and large spontaneous vasomotion was observed in pial vessels. In contrast, the resulting high-density maps showed two anatomically distinct cortical activation sites to anorectal stimulation. CONCLUSIONS & INFERENCES: There are two distinct sites of activation on the parietal cortex following anorectal stimulation in the rat. The implications for sacral neuromodulation as a therapy for fecal incontinence are discussed.


Asunto(s)
Canal Anal/inervación , Mapeo Encefálico/métodos , Potenciales Evocados Somatosensoriales , Ratas/anatomía & histología , Recto/inervación , Corteza Somatosensorial/fisiología , Vías Aferentes/anatomía & histología , Animales , Estimulación Eléctrica , Electrodos , Femenino , Piamadre/irrigación sanguínea , Ratas Wistar , Raíces Nerviosas Espinales/anatomía & histología , Raíces Nerviosas Espinales/fisiología , Sistema Vasomotor/anatomía & histología , Sistema Vasomotor/fisiología
15.
Trials ; 19(1): 336, 2018 Jun 26.
Artículo en Inglés | MEDLINE | ID: mdl-29941019

RESUMEN

BACKGROUND: Faecal incontinence (FI) is a substantial health problem with a prevalence of approximately 8% in community-dwelling populations. Sacral neuromodulation (SNM) is considered the first-line surgical treatment option in adults with FI in whom conservative therapies have failed. The clinical efficacy of SNM has never been rigorously determined in a trial setting and the underlying mechanism of action remains unclear. METHODS/DESIGN: The design encompasses a multicentre, randomised, double-blind crossover trial and cohort follow-up study. Ninety participants will be randomised to one of two groups (SNM/SHAM or SHAM/SNM) in an allocation ratio of 1:1. The main inclusion criteria will be adults aged 18-75 years meeting Rome III and ICI definitions of FI, who have failed non-surgical treatments to the UK standard, who have a minimum of eight FI episodes in a 4-week screening period, and who are clinically suitable for SNM. The primary objective is to estimate the clinical efficacy of sub-sensory SNM vs. SHAM at 32 weeks based on the primary outcome of frequency of FI episodes using a 4-week paper diary, using mixed Poisson regression analysis on the intention-to-treat principle. The study is powered (0.9) to detect a 30% reduction in frequency of FI episodes between sub-sensory SNM and SHAM stimulation over a 32-week crossover period. Secondary objectives include: measurement of established and new clinical outcomes after 1 year of therapy using new (2017 published) optimised therapy (with standardised SNM-lead placement); validation of new electronic outcome measures (events) and a device to record them, and identification of potential biological effects of SNM on underlying anorectal afferent neuronal pathophysiology (hypothesis: SNM leads to increased frequency of perceived transient anal sphincter relaxations; improved conscious sensation of defaecatory urge and cortical/subcortical changes in afferent responses to anorectal electrical stimulation (main techniques: high-resolution anorectal manometry and magnetoencephalography). DISCUSSION: This trial will determine clinical effect size for sub-sensory chronic electrical stimulation of the sacral innervation. It will provide experimental evidence of modifiable afferent neurophysiology that may aid future patient selection as well as a basic understanding of the pathophysiology of FI. TRIAL REGISTRATION: International Standard Randomised Controlled Trial Number: ISRCTN98760715 . Registered on 15 September 2017.


Asunto(s)
Defecación , Incontinencia Fecal/terapia , Plexo Lumbosacro , Estimulación Eléctrica Transcutánea del Nervio/métodos , Adolescente , Adulto , Anciano , Estudios Cruzados , Método Doble Ciego , Incontinencia Fecal/diagnóstico , Incontinencia Fecal/fisiopatología , Femenino , Alemania , Humanos , Irlanda , Masculino , Persona de Mediana Edad , Estudios Multicéntricos como Asunto , Ensayos Clínicos Controlados Aleatorios como Asunto , Recuperación de la Función , Factores de Tiempo , Resultado del Tratamiento , Reino Unido , Adulto Joven
16.
Clin Exp Gastroenterol ; 11: 29-37, 2018.
Artículo en Inglés | MEDLINE | ID: mdl-29391821

RESUMEN

AIM: The epithelial layer within the colon represents a physical barrier between the luminal contents and its underlying mucosa. It plays a pivotal role in mucosal homeostasis, and both tolerance and anti-pathogenic immune responses. Identifying signals of inflammation initiation and responses to stimuli from within the epithelial layer is critical to understanding the molecular pathways underlying disease pathology. This study validated a method to isolate and analyze epithelial populations, enabling investigations of epithelial function and response in a variety of disease setting. MATERIALS AND METHODS: Epithelial cells were isolated from whole mucosal biopsies harvested from healthy controls and patients with active ulcerative colitis by calcium chelation. The purity of isolated cells was assessed by flow cytometry. The expression profiles of a panel of epithelial functional genes were investigated by reverse transcription-polymerase chain reaction (PCR) in isolated epithelial cells and corresponding mucosal biopsies. The expression profiles of isolated cells and corresponding mucosal biopsies were evaluated and compared between healthy and inflamed colonic tissue. RESULTS: Flow cytometry identified 97% of cells isolated as intestinal epithelial cells (IECs). Comparisons of gene expression profiles between the mucosal biopsies and isolated IECs demonstrated clear differences in the gene expression signatures. Sixty percent of the examined genes showed contrasting trends of expression between sample types. CONCLUSION: The calcium chelation isolation method provided a reliable method for the isolation of a pure population of cells with preservation of epithelial cell-specific gene expression. This demonstrates the importance of sample choice when investigating functions directly affecting the colonic epithelial layer.

17.
Am J Surg Pathol ; 42(1): 60-68, 2018 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-29112018

RESUMEN

Mismatch repair deficient (dMMR) colorectal cancer (CRC) despite its association with poor histologic grade often has improved prognosis compared with MMR proficient CRC. Tumor budding and poorly differentiated clusters (PDCs) may predict metastatic potential of colorectal adenocarcinoma (CRC). In addition, their assessment may be more reproducible than the evaluation of other histopathologic parameters. Therefore, we wished to determine their potential as prognostic indicators in a cohort of dMMR CRC patients relative to histologic grade. We investigated the predictive value of conventional WHO grade, budding, PDC grade and other histopathologic parameters on the presence of lymph node metastasis (LNM) and clinical outcome in 238 dMMR CRCs. MMR status was determined by immunohistochemistry for the mismatch repair proteins hMLH1, hMSH2, hMSH6, and hPMS2. Tumor budding and PDCs were highly correlated (r=0.701; P<0.000). Both budding and PDC grade were associated with WHO grade, perineural invasion, lympho-vascular invasion, and extramural vascular invasion, and the presence of LNM in dMMR CRC (P<0.009). Independent predictors of LNM were PDC grade (odds ratio, 4.12; 95% confidence interval [CI], 1.69-10.04; P=0.011) and EMVI (odds ratio, 3.81; 95% CI, 1.56-9.19; P<0.000). Only pTstage (hazard ratio [HR], 4.11; 95% CI, 1.48-11.36; P=0.007) and tumor budding (HR, 2.99; 95% CI, 1.72-5.19; P<0.000) were independently associated with worse disease-free survival (DFS). If tumor budding was excluded from the model, PDC grade became significant for DFS (HR, 2.34; 95% CI, 1.34-4.09; P=0.003). WHO Grade does not independently correlate with clinical outcome in dMMR CRC. PDC grade and extramural vascular invasion are independent predictors of LNM. Tumor budding and pTstage are the best predictors of DFS. If tumor budding cannot be assessed, PDC grade may be used as a prognostic surrogate.


Asunto(s)
Adenocarcinoma/diagnóstico , Adenocarcinoma/patología , Neoplasias Colorrectales/diagnóstico , Neoplasias Colorrectales/patología , Reparación de la Incompatibilidad de ADN , Adenocarcinoma/genética , Adenocarcinoma/mortalidad , Adulto , Anciano , Anciano de 80 o más Años , Biomarcadores de Tumor/genética , Neoplasias Colorrectales/genética , Neoplasias Colorrectales/mortalidad , Femenino , Estudios de Seguimiento , Humanos , Inmunohistoquímica , Modelos Logísticos , Metástasis Linfática , Masculino , Persona de Mediana Edad , Clasificación del Tumor , Estadificación de Neoplasias , Pronóstico , Estudios Retrospectivos , Análisis de Supervivencia
18.
Dis Colon Rectum ; 60(6): 614-626, 2017 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-28481856

RESUMEN

BACKGROUND: Fecal incontinence is a common disorder, but its pathophysiology is not completely understood. OBJECTIVE: The aim of this review is to present animal models that have a place in the study of fecal incontinence. DATA SOURCES: A literature review following Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines performed in August 2016 revealed 50 articles of interest. Search terms included fecal/faecal incontinence and animal model or specific species. STUDY SELECTION: Articles not describing an animal model, in vitro studies, veterinary literature, reviews, and non-English articles were excluded. MAIN OUTCOME MEASURES: The articles described models in rats (n = 31), dogs (n = 8), rabbits (n = 7), and pigs (n = 4). RESULTS: Different fecal incontinence etiologies were modeled, including anal sphincter lesions (33 articles) ranging from a single anal sphincter cut to destruction of 50% of the anal sphincter by sharp dissection, electrocautery, or diathermy. Neuropathic fecal incontinence (12 articles) was achieved by complete or incomplete pudendal, pelvic, or inferior rectal nerve damage. Mixed fecal incontinence (5 articles) was modeled either by the inflation of pelvic balloons or an array of several lesions including nervous and muscular damage. Anal fistulas (2 articles), anal sphincter resection (3 articles), and diabetic neuropathy (2 articles) were studied to a lesser extent. LIMITATIONS: Bias may have arisen from the authors' own work on fecal incontinence and the absence of blinding to the origins of articles. CONCLUSIONS: Validated animal models representing the main etiologies of fecal incontinence exist, but no animal model to date represents the whole pathophysiology of fecal incontinence. Therefore, the individual research questions still dictate the choice of model and species.


Asunto(s)
Modelos Animales de Enfermedad , Incontinencia Fecal/etiología , Canal Anal/lesiones , Canal Anal/cirugía , Animales , Neuropatías Diabéticas/complicaciones , Perros , Nervio Pudendo/lesiones , Conejos , Ratas , Fístula Rectal/complicaciones , Porcinos
20.
Gut Microbes ; 7(5): 435-42, 2016 09 02.
Artículo en Inglés | MEDLINE | ID: mdl-27662587

RESUMEN

The relevance of biogeography to the distal gut microbiota has been investigated in both health and inflammatory bowel disease (IBD), however multiple factors, including sample type and methodology, microbiota characterization and interpersonal variability make the construction of a core model of colonic biogeography challenging. In addition, how phylogenetic classification relates to immunogenicity and whether consistent alterations in the microbiota are associated with ulcerative colitis (UC) remain open questions. This addendum seeks to review the human colonic microbiota in health and UC as currently understood, in the broader context of the human microbiome.


Asunto(s)
Bacterias/aislamiento & purificación , Colitis Ulcerosa/microbiología , Colon/microbiología , Microbioma Gastrointestinal , Animales , Bacterias/clasificación , Bacterias/genética , Colitis Ulcerosa/inmunología , Colon/inmunología , Salud , Humanos , Filogenia
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