Barium defecography can assess structural and functional abnormalities in patients with chronic constipation.
The purpose of this study was to determine the prevalence of individual and overlapping ...defecographic findings in this setting.
This was a cross-sectional study.
The study was conducted at a university hospital tertiary GI physiology department.
Consecutive examinations of 827 consecutive patients presenting over a 30-month period with well-defined symptom severity (≥12 points on the Cleveland Clinic Constipation score) were included. Systematic evaluation of images with results stratified by sex is described.
Six individual functional or anatomic (intussusception, rectocele, enterocele, megarectum, excessive dynamic perineal descent) defecographic observations were defined a priori, thus permitting 26 possible combinations of findings (ie, 63 abnormal types + 1 normal).
Patients with constipation (mean symptom score = 19) were predominantly female (88%), with median age of 49 years (range, 17-98 y) . All 6 individual radiologic findings were identified with a total of 43 combinations found in the cohort; the 14 most prevalent of these accounted for >85% of patients. Only 136 patients (16.4%) had a normal defecography (34.3% males vs 13.9% females; p < 0.0001). Overall, 612 patients (74.0%) had structural (n = 508 (61.4%)) or functional (n=104 (12.6%)) abnormalities in isolation, with 79 (9.6%) others exhibiting combinations of both. Functional abnormalities in isolation were more common in males compared with females (22.5% vs11.2%; p = 0.025) as opposed to structural abnormalities (57.8% vs 85.7%; p < 0.0001). Expulsion time was longer in females compared with males (110 s (60-120 s) vs 90 s (60-120 s); p = 0.049).
The study was limited by its lack of multiorgan opacification.
These results provide a contemporary atlas of defecographic findings in constipation. Several individual structural and functional features have been systematically classified, with overlap greater than previously acknowledged and profound differences among sexes that carry implications for tailoring management. See Video Abstract at http://links.lww.com/DCR/B552.
ANTECEDENTES:La defecografía con bario puede evaluar anomalías estructurales y funcionales en pacientes con estreñimiento crónico.OBJETIVO:Determinar la prevalencia de hallazgos defecográficos individuales y superpuestos en este entorno.DISEÑO:Transversal.ENTORNO CLINICO:Hospital Universitario de tercer nivel, departamento de fisiología gastrointestinal.PACIENTES:Exploraciones consecutivas de 827 pacientes consecutivos que se presentaron durante un período de 30 meses con una gravedad de los síntomas bien definida (≥12 puntos en la escala de estreñimiento de la Cleveland Clinic): evaluación sistemática de imágenes con resultados estratificados por sexo.PRINCIPALES MEDIDAS DE VALORACION:Se definieron a priori seis observaciones defecográficas individuales, funcionales o anatómicas (intususcepción, rectocele, enterocele, megarecto, descenso perineal dinámico excesivo), lo que permitió 26 combinaciones posibles de hallazgos (es decir, 63 tipos anormales + 1 normal).RESULTADOS:Los pacientes con estreñimiento (puntuación media de síntomas, 19) eran predominantemente mujeres (88%) con una edad mediana de 49 (17-98) años. Se identificaron 6 hallazgos radiológicos individuales con un total de 43 combinaciones encontradas en la cohorte; los 14 más predominantes de éstos representaron >85% de los pacientes.Solo 136 (16,4%) pacientes tuvieron una defecografía normal (34,3% hombres vs. 13,9% mujeres; P < 0,0001). En general, 612 (74,0%) pacientes tenían anomalías estructurales (n = 508 61,4%) o funcionales (n = 104 12,6%) de forma aislada, y otros 79 (9,6%) presentaban combinaciones de ambas. Las anomalías funcionales aisladas fueron más comunes en los hombres en comparación con las mujeres (22,5% vs. 11,2%, P = 0,025) en comparación con las anomalías estructurales (57,8 vs. 85,7%, P < 0,0001). El tiempo de expulsión fue mayor en las mujeres en comparación con los hombres (110 60-120 vs. 90 60-120 segundos; P = 0,049).LIMITACIONES:Falta de opacificación multiorgánica.CONCLUSIONES:Estos resultados proporcionan un atlas contemporáneo de hallazgos defecográficos en estreñimiento. Varias características individuales, estructurales y funcionales; se han clasificado sistemáticamente, con una superposición mayor que la reconocida anteriormente y con grandes diferencias entre los sexos que tienen implicaciones para adaptar su tratamiento. Consulte Video Resumen en http://links.lww.com/DCR/B552.
Rectal cancer is common with a 60% 5-year survival rate. Treatment usually involves surgery with or without neoadjuvant chemoradiotherapy or adjuvant chemotherapy. Sphincter saving curative treatment ...can result in debilitating changes to bowel function known as low anterior resection syndrome (LARS). There are currently no clear guidelines on the management of LARS with only limited evidence for different treatment modalities.
Patients who have undergone an anterior resection for rectal cancer in the last 10 years will be approached for the study. The feasibility trial will take place in four centres with a 9-month recruitment window and 12 months follow-up period. The primary objective is to assess the feasibility of recruitment to the POLARiS trial which will be achieved through assessment of recruitment, retainment and follow-up rates as well as the prevalence of major LARS.Feasibility outcomes will be analysed descriptively through the estimation of proportions with confidence intervals. Longitudinal patient reported outcome measures will be analysed according to scoring manuals and presented descriptively with reporting graphically over time.
Ethical approval has been granted by Wales REC1; Reference 22/WA/0025. The feasibility study is in the process of set up. The results of the feasibility trial will feed into the design of an expanded, international trial.
CT05319054.
Skeletal muscle-derived cells (SMDC) hold tremendous potential for replenishing dysfunctional muscle lost due to disease or trauma. Current therapeutic usage of SMDC relies on harvesting autologous ...cells from muscle biopsies that are subsequently expanded in vitro before re-implantation into the patient. Heterogeneity can arise from multiple factors including quality of the starting biopsy, age and comorbidity affecting the processed SMDC. Quality attributes intended for clinical use often focus on minimum levels of myogenic cell marker expression. Such approaches do not evaluate the likelihood of SMDC to differentiate and form myofibres when implanted in vivo, which ultimately determines the likelihood of muscle regeneration. Predicting the therapeutic potency of SMDC in vitro prior to implantation is key to developing successful therapeutics in regenerative medicine and reducing implementation costs. Here, we report on the development of a novel SMDC profiling tool to examine populations of cells in vitro derived from different donors. We developed an image-based pipeline to quantify morphological features and extracted cell shape descriptors. We investigated whether these could predict heterogeneity in the formation of myotubes and correlate with the myogenic fusion index. Several of the early cell shape characteristics were found to negatively correlate with the fusion index. These included total area occupied by cells, area shape, bounding box area, compactness, equivalent diameter, minimum ferret diameter, minor axis length and perimeter of SMDC at 24 h after initiating culture. The information extracted with our approach indicates live cell imaging can detect a range of cell phenotypes based on cell-shape alone and preserving cell integrity could be used to predict propensity to form myotubes in vitro and functional tissue in vivo.
Guidelines on histopathological techniques and reporting for adult and paediatric gastrointestinal neuromuscular pathology have been produced recently by an international working group (IWG). These ...addressed the important but relatively neglected areas of histopathological practice of the general pathologist, including suction rectal biopsy and full-thickness intestinal tissue. Recommendations were presented for the indications, safe acquisition of tissue, histological techniques, reporting and referral of such histological material.
Consensual processes undertaken by the IWG and following established guideline decision group methodologies.
This report presents a contemporary and structured classification of gastrointestinal neuromuscular pathology based on defined histopathological criteria derived from the existing guidelines. In recognition of its origins and first presentation in London at the World Congress of Gastroenterology 2009, this has been named 'The London Classification'. The implementation of this classification should allow some diagnostic standardisation, but should necessarily be viewed as a starting point for future modification as new data become available.
Background
In this prospective cohort study, we evaluated features of “adult‐onset megacolon with focal hypoganglionosis.”
Methods
We assessed the radiologic, endoscopic, and histopathologic ...phenotyping and treatment outcomes of 29 patients between 2017 and 2020. Data from community controls, consisting of 19,948 adults undergoing health screenings, were analyzed to identify risk factors. Experts reviewed clinical features and pathological specimens according to the London Classification for gastrointestinal neuromuscular pathology.
Key results
The median age of the patients with adult‐onset megacolon with focal hypoganglionosis at symptom onset was 59 years (range, 32.0–74.9 years), with mean symptom onset only 1 year before diagnosis. All patients had focal stenotic regions with proximal bowel dilatation (mean diameter, 78.8 mm; 95% confidence interval CI, 72–86). The comparison with community controls showed no obvious risk factors. Ten patients underwent surgery, and all exhibited significant hypoganglionosis: 5.4 myenteric ganglion cells/cm (interquartile range IQR, 3.7–16.4) in the stenotic regions compared to 278 cells/cm (IQR, 190–338) in the proximal and 95 cells/cm (IQR, 45–213) in the distal colon. Hypoganglionosis was associated with CD3+ T cells along the myenteric plexus. Colectomy was associated with significant symptom improvement compared to medical treatment change in the Global Bowel Satisfaction score, −5.4 points (surgery) vs. ‐0.3 points (medical treatment); p < 0.001.
Conclusions and inferences
Adult‐onset megacolon with focal hypoganglionosis has distinct features characterized by hypoganglionosis due to inflammation. Bowel resection appears to benefit these patients.
In patients with segmental megacolon with a focally narrowed colonic segment connecting the proximally dilated and distally non‐dilated segments, the focally narrowed segment showed hypoganglionosis. Patients who underwent colectomy showed significant improvements in global bowel satisfaction (GBS) score and bowel frequency per week. Bowel resection appears to benefit these patients.
Human colonic neuromuscular functions decline among the elderly. The aim was to explore the involvement of senescence. A preliminary PCR study looked for age-dependent differences in expression of
...CDKN1A
(encoding the senescence-related p21 protein) and
CDKN2A
(encoding p16 and p14) in human ascending and descending colon (without mucosa) from 39 (approximately 50: 50 male: female) adult (aged 27–60 years) and elderly donors (70–89 years). Other genes from different aging pathways (e.g., inflammation, oxidative stress, autophagy) and cell-types (e.g., neurons, neuron axonal transport) were also examined. Unlike
CDKN1A, CDKN2A
(using primers for p16 and p14 but not when using p14-specific primers) was upregulated in both regions of colon. Compared with the number of genes appearing to upregulate in association with temporal age, more genes positively associated with increased
CDKN2A
expression (respectively, 16 and five of 44 genes studied for ascending and descending colon). Confirmation of increased expression of
CDKN2A
was sought by immunostaining for p16 in the myenteric plexus of colon from 52 patients, using a semi-automated software protocol. The results showed increased staining not within the glial cells (S100 stained), but in the cytoplasm of myenteric nerve cell bodies (MAP2 stained, with identified nucleus) of ascending, but not descending colon of the elderly, and not in the cell nucleus of either region or age group (5,710 neurons analyzed:
n
= 12–14 for each group). It was concluded that increased p16 staining within the cytoplasm of myenteric nerve cell bodies of elderly ascending (but not descending) colon, suggests a region-dependent, post-mitotic cellular senescence-like activity, perhaps involved with aging of enteric neurons within the colon.
The Joint Hypermobility Syndrome (JHS) is a common connective tissue disorder characterized by joint hyperflexibility, dysautonomia, and chronic pain. Gastrointestinal (GI) symptoms are reported in ...JHS patients attending rheumatology clinics, but the prevalence and symptom pattern of previously undiagnosed JHS in GI clinics are unknown.
By using validated questionnaires, a prospective cross-sectional study in secondary care GI clinics estimated the prevalence of JHS in new consecutively referred patients, compared GI symptoms in patients with and without JHS, and by using multiple regression determined whether the burden of GI symptoms in JHS patients was dependent on chronic pain, autonomic, psychological, and medication related factors. A positive control group consisted of JHS patients referred from rheumatology clinics with GI symptoms (JHS-Rh).
From 552 patients recruited, 180 (33%) had JHS (JHS-G) and 372 did not (non-JHS-G). Forty-four JHS-Rh patients were included. JHS-G patients were more likely to be younger, female with poorer quality of life (P = .02) than non-JHS-G patients. After age and sex matching, heartburn (odds ratio OR, 1.66; confidence interval CI, 1.1-2.5; P = .01), water brash (OR, 2.02; CI, 1.3-3.1; P = .001), and postprandial fullness (OR, 1.74; CI, 1.2-2.6; P = .006) were more common in JHS-G vs non-JHS-G. Many upper and lower GI symptoms increased with increasing severity of JHS phenotype. Upper GI symptoms were dependent on autonomic and chronic pain factors.
JHS is common in GI clinics, with increased burden of upper GI and extraintestinal symptoms and poorer quality of life. Recognition of JHS will facilitate multidisciplinary management of GI and extra-GI manifestations.
To present methods and baseline results for an online screening tool to identify increased risk for Parkinson's disease (PD) in the UK population.
Risk estimates for future PD were derived from the ...results of a systematic review of risk factors and early features of PD. Participants aged 60-80 years without PD were recruited by self-referral. They completed an online survey (including family history, non-motor symptoms and lifestyle factors), a keyboard-tapping task and the University of Pennsylvania Smell Identification Test. Risk scores were calculated based on survey answers. Preliminary support for the validity of this algorithm was assessed by comparing those estimated to be higher risk for PD with those at lower risk using proxies, including smell loss, REM-sleep behaviour disorder and reduced tapping speed, and by assessing associations in the whole group.
1324 eligible participants completed the survey and 1146 undertook the keyboard-tapping task. Smell tests were sent to 1065 participants. Comparing the 100 highest-risk participants and 100 lowest-risk participants, median University of Pennsylvania Smell Identification Test scores were 30/40 versus 33/40 (p<0.001), mean number of key taps in 30 s were 55 versus 58 (p=0.045), and 24% versus 10% scored above cut-off for REM-sleep behaviour disorder (p=0.008). Regression analyses showed increasing risk scores were associated with worse scores in the three proxies across the whole group (p≤0.001).
PREDICT-PD is the first study to systematically combine risk factors for PD in the general population. Validity to predict risk of PD will be tested through longitudinal follow-up of incident PD diagnosis.
Autonomic nervous system dysfunction has been implicated in visceral hypersensitivity. However, the specific contribution of the parasympathetic nervous system (PNS) is unclear. We aimed to determine ...whether physiological and pharmacological manipulation of parasympathetic tone influences the development of hypersensitivity in a validated model of acid-induced oesophageal pain.
Prior to, and following, a 30-min distal oesophageal infusion of 0.15 M hydrochloric acid, pain thresholds to electrical stimulation were determined in the proximal non-acid exposed oesophagus in healthy subjects. Validated sympathetic (skin conductance response) and parasympathetic (cardiac vagal tone) parameters were measured at baseline and continuously thereafter. In study 1, 55 subjects were randomised in a pragmatic blinded crossover design to receive deep breathing or un-paced breathing during acid infusion. In study 2, 32 subjects were randomised in a blinded, crossover design to receive intravenous atropine or placebo (saline) with deep breathing during acid infusion.
Study 1: Deep breathing increased cardiac vagal tone (2.1±2.3 vs -0.3±2.3, p=0.0006) with concomitant withdrawal of skin conductance response (-0.6±4.9 vs 3±4.8, p=0.03) in comparison with un-paced breathing. Deep breathing prevented the development of acid-induced oesophageal hypersensitivity in comparison with sham breathing (p=0.0001). Study 2: Atropine, in comparison with placebo, blocked the attenuating effect of deep breathing on the development of acid-induced oesophageal hypersensitivity (p=0.046).
The development of oesophageal hyperalgesia is prevented by physiologically increasing parasympathetic tone. This effect is pharmacologically blocked with atropine, providing evidence that the PNS influences the development of oesophageal pain hypersensitivity.
In contrast to paediatric and geriatric populations, faecal incontinence and constipation in adults are generally considered separate entities. This may be incorrect.
Cross-sectional study of ...consecutive patients (18–80 years) referred to a tertiary unit (2004–2016) for investigation of refractory faecal incontinence and/or constipation and meeting Rome IV core criteria (applied post-hoc) for self-reported symptoms. We sought to determine how frequently both diagnoses coexisted, how frequently coexistent diagnoses were recognised by the referring clinician and to evaluate differences in clinical characteristics between patients with single or both diagnoses.
Study sample consisted of 4,027 patients (3,370 females 83·7%). According to Rome IV criteria, 807 (20·0%) patients self-reported faecal incontinence in isolation, 1,569 (39·0%) patients had functional constipation in isolation, and 1,651 (41·0%) met criteria for both diagnoses (coexistent symptoms). In contrast, only 331 (8·2%) patients were referred for coexistent symptoms. Of the 1,651 patients with self-reported coexistent symptoms, only 225 (13·6%) were recognised by the referrer i.e. 86·4% were missed. Coexistent symptoms were most often missed in patients referred for faecal incontinence in isolation. In this group of 1,640 patients, 765 (46·7%) had concomitant symptoms of functional constipation. Opioid usage, comorbidities, childhood bowel problems, mixed incontinence symptoms, prolapse symptoms and structural abnormalities on defaecography were associated with reclassification.
Over 40% of adults referred for anorectal physiological investigation had coexistent diagnoses of faecal incontinence and functional constipation, based on validated criteria. This overlap is overlooked by referrers, poorly documented in current literature, and may impact management.
PDF
