Relation between the internal anal sphincter and defecation disorders in patients with anorectal malformations.

OBJECTIVES: To investigate associations between the rectoanal inhibitory reflex (RAIR), type of congenital anorectal malformations (ARMs), type of operation that patients with ARM had undergone, and objectively measured fecal incontinence and defecation problems. METHODS: We retrospectively included 69 pediatric patients with ARM. All underwent anorectal function tests at the University Medical Center of Groningen during the last 10 years. We assessed anorectal physiology using the Rome IV criteria and anorectal function tests. RESULTS: We found the reflex in 67% of patients and all types of ARMs. All patients who had not been operated on, and those who had undergone less extensive surgery possessed the reflex. In contrast, patients who underwent posterior sagittal anorectoplasty, 44% possessed it. We found no difference between mean rectal volumes in patients with and without the reflex (251 mL vs. 325 mL, respectively, p = 0.266). We found that over time, patients without the reflex seemed to develop significantly higher rectal volumes than patients who had it. We did not find a significant difference between the reflex and fecal incontinence; however, it seems that the absence of the reflex, resting anal sphincter pressure, and fecal incontinence are related. CONCLUSION: The RAIR seems present in patients with ARM irrespective of their malformation type. Corrective surgery, however, may impair this reflex. Seemingly, its absence results in constipation with enlarged rectal volumes and fecal incontinence. Every effort should be made to preserve this reflex during surgery and to use extensive surgical procedures as sparingly as possible.

PARK7/DJ-1 deficiency impairs microglial activation in response to LPS-induced inflammation.

BACKGROUND: Specific microglia responses are thought to contribute to the development and progression of neurodegenerative diseases, including Parkinson's disease (PD). However, the phenotypic acquisition of microglial cells and their role during the underlying neuroinflammatory processes remain largely elusive. Here, according to the multiple-hit hypothesis, which stipulates that PD etiology is determined by a combination of genetics and various environmental risk factors, we investigate microglial transcriptional programs and morphological adaptations under PARK7/DJ-1 deficiency, a genetic cause of PD, during lipopolysaccharide (LPS)-induced inflammation. METHODS: Using a combination of single-cell RNA-sequencing, bulk RNA-sequencing, multicolor flow cytometry and immunofluorescence analyses, we comprehensively compared microglial cell phenotypic characteristics in PARK7/DJ-1 knock-out (KO) with wildtype littermate mice following 6- or 24-h intraperitoneal injection with LPS. For translational perspectives, we conducted corresponding analyses in human PARK7/DJ-1 mutant induced pluripotent stem cell (iPSC)-derived microglia and murine bone marrow-derived macrophages (BMDMs). RESULTS: By excluding the contribution of other immune brain resident and peripheral cells, we show that microglia acutely isolated from PARK7/DJ-1 KO mice display a distinct phenotype, specially related to type II interferon and DNA damage response signaling, when compared with wildtype microglia, in response to LPS. We also detected discrete signatures in human PARK7/DJ-1 mutant iPSC-derived microglia and BMDMs from PARK7/DJ-1 KO mice. These specific transcriptional signatures were reflected at the morphological level, with microglia in LPS-treated PARK7/DJ-1 KO mice showing a less amoeboid cell shape compared to wildtype mice, both at 6 and 24 h after acute inflammation, as also observed in BMDMs. CONCLUSIONS: Taken together, our results show that, under inflammatory conditions, PARK7/DJ-1 deficiency skews microglia towards a distinct phenotype characterized by downregulation of genes involved in type II interferon signaling and a less prominent amoeboid morphology compared to wildtype microglia. These findings suggest that the underlying oxidative stress associated with the lack of PARK7/DJ-1 affects microglia neuroinflammatory responses, which may play a causative role in PD onset and progression.

Association of Constipation with Modes of Delivery: A Retrospective Questionnaire-based Study.

INTRODUCTION AND HYPOTHESIS: Pelvic floor damage can contribute to pelvic floor dysfunction, including constipation. Most studies focus on constipation during pregnancy, whereas information regarding the mode of delivery in relation to constipation is limited. We hypothesise that women with a history of vaginal delivery report constipation more often than women with a history of caesarean section. METHODS: This was a retrospective cross-sectional multicentre study conducted in the Netherlands. All included patients (n = 2,643) completed the Groningen Defecation and Fecal Continence questionnaire to assess bowel problems of the last 6 months. Parametric tests, Chi-squared, univariable and multivariable regression analyses were performed. RESULTS: Among 2,643 parous women, 2,248 delivered vaginally (85.1%) and 395 (14.9%) by caesarean section. Altogether, 649 women (24.6%) suffered from constipation. Women in the vaginal delivery group were constipated more often than women in the caesarean section group (25.5% versus 19.0%, p = 0.005). For women who had delivered vaginally, multivariable regression analysis showed an odds ratio for constipation of 1.47 (95% confidence interval, 1.109-1.938, p = 0.007). The odds ratio for constipation in women with a spontaneous perineal tear was 1.4 times higher than in women with an intact perineum (p = 0.030). Furthermore, the vaginal delivery group reported difficulties regarding bowel emptying (p = 0.048), straining (p = 0.027), incomplete defecation (p = 0.043), not able to defecate daily (p = 0.018), manually assisted defecation (p = 0.015) and had higher Renzi scores (p = 0.043) more often. CONCLUSIONS: Women in the vaginal delivery group have higher prevalences and odds ratios for constipation. Furthermore, a perineal tear during vaginal delivery increases the odds ratio for constipation.

Age-specific reference scores for the PISQ-12 on female sexual functioning in the Netherlands: a retrospective population-based survey.

BACKGROUND: Female sexual dysfunction is common in the general population, with age emerging as a significant determinant of sexual activity and functioning. AIM: To establish age-specific reference scores for the Pelvic Organ Prolapse/Urinary Incontinence Sexual Questionnaire (PISQ-12) in the general Dutch female population. METHODS: A retrospective, cross-sectional, questionnaire-based study was conducted in the Netherlands. The study population comprised 2518 Dutch-speaking women aged ≥18 years, representing a cross section of the general Dutch population. The PISQ-12 was used to assess sexual functioning in heterosexual women. The Groningen Defecation and Fecal Continence questionnaire was utilized to demonstrate demographic factors. OUTCOMES: We established age-specific reference scores for the PISQ-12 in the general Dutch population. RESULTS: Of the 2518 women, 1592 (63.2%) were sexually active and 926 (36.8%) were not. Further analysis focused on the sexually active group: we found a decrease in mean total PISQ scores, ranging from 38.34 among 18- to 34-year-olds to 36.98 among ≥65-year-olds. Older women scored lower in the behavior domain, specifically pertaining to sexual desire (P < .001) and sexual excitement (P < .001). They also had lower scores in the partner-related domain regarding partner problems of erection (P < .001) and orgasm perception (P < .001). With increasing age, negative emotional reaction scores were higher (P < .001). In the physical domain, we observed significantly different scores for pain during sexual intercourse (P < .001) and restrictions in sexual activity due to fear of urinary leakage (P < .001), with the lowest scores in the youngest group. CLINICAL IMPLICATIONS: These age-specific references scores of the PISQ-12 provide an overview of sexual functioning of a general population, which enables caregivers to assess and interpret patients' individual scores more accurately. STRENGTHS AND LIMITATIONS: We included only sexually active women in our subanalyses, potentially introducing selection bias for older women with better physical conditions. The study's strength lies in its extensive sample size, representing a cross section of the general Dutch population. Furthermore, the self-administered questionnaire approach helped minimize embarrassment and obtain realistic responses. CONCLUSION: Our study demonstrated age-specific PISQ-12 reference scores and highlighted associations between aging and diminishing scores of sexual desire, sexual excitement, erection problems, and orgasm perception, while women aged 18 to 34 years reported the lowest scores for pain during intercourse and limited sexual activity due to fear of urinary leakage.

Alpha-synuclein pathology is associated with astrocyte senescence in a midbrain organoid model of familial Parkinson's disease.

Parkinson's disease (PD) is a complex, progressive neurodegenerative disease characterized by the loss of dopaminergic neurons in the substantia nigra pars compacta in the midbrain. Despite extensive research efforts, the molecular and cellular changes that precede neurodegeneration in PD are poorly understood. To address this, here we describe the use of patient specific human midbrain organoids harboring the SNCA triplication to investigate mechanisms underlying dopaminergic degeneration. Our midbrain organoid model recapitulates key pathological hallmarks of PD, including the aggregation of α-synuclein and the progressive loss of dopaminergic neurons. We found that these pathological hallmarks are associated with an increase in senescence associated cellular phenotypes in astrocytes including nuclear lamina defects, the presence of senescence associated heterochromatin foci, and the upregulation of cell cycle arrest genes. These results suggest a role of pathological α-synuclein in inducing astrosenescence which may, in turn, increase the vulnerability of dopaminergic neurons to degeneration.

The Severity of Fecal Problems Is Negatively Associated With Quality of Life in a Dutch Population Without Bowel Function Comorbidities.

BACKGROUND: Constipation and fecal incontinence negatively influence quality of life. The association between the severity of fecal problems and quality of life has not been investigated in the general population without bowel function comorbidities. OBJECTIVE: To investigate the association between the severity of constipation and fecal incontinence and quality of life in patients without comorbidities influencing bowel function. DESIGN: A population-based, cross-sectional study. SETTINGS: The study involved 3668 Dutch study participants. PATIENTS: A survey company conducted a population-wide study of the general Dutch population. Altogether, 5000 Dutch citizens completed the Groningen Defecation and Fecal Continence and Short Form-36 questionnaires. The data on 3668 respondents without comorbidities that could influence bowel function were included for analysis (study group). MAIN OUTCOME MEASURES: The severity of constipation (Agachan score) and fecal incontinence (Wexner score) in relation to the quality-of-life scores. RESULTS: In the study group (n = 3668), 487 had constipation (13.3%), 116 had fecal incontinence (3.2%), and 64 had 2 coexisting fecal problems (1.7%). In the multivariable analysis, all quality-of-life domains were negatively associated with the severity of constipation and fecal incontinence. The associations between the severity of constipation and quality of life were stronger (highest: ß = -2.413; 95% CI, -2.681 to -2.145; p < 0.001) than those of fecal incontinence (highest: ß = -1.280; 95% CI, -1.681 to -.880; p < 0.001). We also found that a longer duration of bowel complaints coincided with higher severity scores, especially for constipation. Respondents mostly rated their defecation health as positive, regardless of the severity of their fecal problems. LIMITATIONS: Cross-sectional design. CONCLUSIONS: The severity of constipation and fecal incontinence is significantly associated with reduced quality of life, with the severity of constipation having stronger associations than fecal incontinence. Given respondents' unawareness of their fecal problems and the progressive character, timely intervention is advocated. See Video Abstract . LA GRAVEDAD DE LOS PROBLEMAS FECALES SE ASOCIA NEGATIVAMENTE CON LA CALIDAD DE VIDA EN UNA POBLACIN HOLANDESA SIN COMORBILIDADES DE LA FUNCIN INTESTINAL: ANTECEDENTES:El estreñimiento y la incontinencia fecal influyen negativamente en la calidad de vida. La asociación entre la gravedad de los problemas fecales y la calidad de vida no se ha investigado en la población general sin comorbilidades de la función intestinal.OBJETIVO:Investigar la asociación entre la gravedad del estreñimiento y la incontinencia fecal y la calidad de vida en la población holandesa general sin comorbilidades que influyan en la función intestinal.DISEÑO:Estudio transversal de base poblacional.ENTORNO CLINICO:El estudio involucró a 3668 participantes holandeses.PACIENTES:Una empresa de encuestas realizó un estudio poblacional de la población holandesa en general. En total, 5.000 ciudadanos holandeses completaron los cuestionarios Groningen Defecation and Fecal Continence y Short-Form 36. Se incluyeron para el análisis los datos de 3668 encuestados sin comorbilidades que pudieran influir en la función intestinal (grupo de estudio).PRINCIPALES MEDIDAS DE RESULTADO:La gravedad del estreñimiento (puntuación de Agachan) y la incontinencia fecal (puntuación de Wexner) en relación con las puntuaciones de calidad de vida.RESULTADOS:En el grupo de estudio (n = 3668), 487 tenían estreñimiento (13,3%), 116 tenían incontinencia fecal (3,2%) y 64 tenían 2 problemas fecales coexistentes (1,7%). En el análisis multivariable, todos los dominios de calidad de vida se asociaron negativamente con la gravedad del estreñimiento y la incontinencia fecal. Las asociaciones entre la gravedad del estreñimiento y la calidad de vida fueron más fuertes (más alta: ß = -2,413; IC del 95 %, -2,681 a -2,145; p < 0,001) que las de la incontinencia fecal (más alta: ß = -1,280; 95 IC %: -1,681 a -0,880; p < 0,001). También encontramos que una mayor duración de las molestias intestinales coincidió con puntuaciones de gravedad más altas, especialmente para el estreñimiento. La mayoría de los encuestados calificaron su salud en la defecación como positiva, independientemente de la gravedad de sus problemas fecales.LIMITACIONES:Diseño transversal.CONCLUSIONES:La gravedad del estreñimiento y la incontinencia fecal se asocia significativamente con una calidad de vida reducida; la gravedad del estreñimiento tiene asociaciones más fuertes que la incontinencia fecal. Dado el desconocimiento de los encuestados sobre sus problemas fecales y el carácter progresivo, se recomienda una intervención oportuna. (Traducción- Dr. Francisco M. Abarca-Rendon ).

The Effect of a Temporary Stoma on Long-term Functional Outcomes Following Surgery for Rectal Cancer.

BACKGROUND: Patients with rectal cancer may undergo surgical resection with or without a temporary stoma. OBJECTIVE: This study primarily aimed to compare long-term functional outcomes between patients with and without a temporary stoma after surgery for rectal cancer. The secondary aim was to investigate the effect of time to stoma reversal on functional outcomes. DESIGN: This was a multicenter, cross-sectional study. SETTINGS: This study was conducted at 7 Dutch hospitals. PATIENTS: Included were patients who had undergone rectal cancer surgery (2009-2015). Excluded were deceased patients, who were deceased, had a permanent stoma, or had intellectual disability. MAIN OUTCOME MEASURES: Functional outcomes were measured using the Rome IV criteria for constipation and fecal incontinence and the low anterior resection syndrome score. RESULTS: Of 656 patients, 32% received a temporary ileostomy and 20% a temporary colostomy (86% response). Follow-up was at 56 (interquartile range, 38.5-79) months. Patients who had a temporary ileostomy experienced less constipation, more fecal incontinence, and more major low anterior resection syndrome than those without a temporary stoma. Patients who had a temporary colostomy experienced more major low anterior resection syndrome than those without a temporary stoma. A temporary ileostomy or colostomy was not associated with constipation or fecal incontinence after correction for confounding factors (eg, anastomotic height, anastomotic leakage, radiotherapy). Time to stoma reversal was not associated with constipation, fecal incontinence, or major low anterior resection syndrome. LIMITATIONS: Cross-sectional design. CONCLUSIONS: Although patients with a temporary ileostomy or colostomy have worse functional outcomes in the long term, it seems that the reason for creating a temporary stoma, rather than the stoma itself, underlies this phenomenon. Time to reversal of a temporary stoma does not influence functional outcomes. See Video Abstract . EL EFECTO DEL ESTOMA TEMPORAL SOBRE LOS RESULTADOS FUNCIONALES A LARGO PLAZO DESPUS DE LA CIRUGA POR CNCER DE RECTO: ANTECEDENTES:Los pacientes con cáncer de recto pueden someterse a resección quirúrgica con o sin un estoma temporal.OBJETIVO:El objetivo principal de este estudio fue comparar los resultados funcionales a largo plazo entre pacientes con y sin estoma temporal después de cirugía por cáncer de recto. El objetivo secundario fue investigar el efecto del tiempo transcurrido hasta la reversión del estoma sobre los resultados funcionales.DISEÑO:Este fue un estudio transversal multicéntrico.ESCENARIO:Este estudio se llevó a cabo en siete hospitales holandeses.PACIENTES:Se incluyeron pacientes sometidos a cirugía de cáncer de recto (2009-2015). Se excluyeron pacientes fallecidos, pacientes con estoma permanente o discapacidad intelectual.PRINCIPALES MEDIDAS DE RESULTADO:Los resultados funcionales se midieron utilizando los criterios de Roma IV para el estreñimiento y la incontinencia fecal y la puntuación del síndrome de resección anterior baja (LARS).RESULTADOS:De 656 pacientes, el 32% recibió una ileostomía temporal y el 20% una colostomía temporal (respuesta del 86%). El seguimiento fue de 56.0 (RIQ 38.5-79.0) meses. Los pacientes a los que se les realizó una ileostomía temporal experimentaron menos estreñimiento, más incontinencia fecal y más LARS mayor que los pacientes sin un estoma temporal. Los pacientes que tuvieron una colostomía temporal experimentaron más LARS mayor que los pacientes sin un estoma temporal. Una ileostomía o colostomía temporal no se asoció con estreñimiento o incontinencia fecal después de la corrección de factores de confusión (p. ej., altura anastomótica, fuga anastomótica, radioterapia). El tiempo hasta la reversión del estoma no se asoció con estreñimiento, incontinencia fecal o LARS mayor.LIMITACIONES:El presente estudio está limitado por su diseño transversal.CONCLUSIONES:Aunque los pacientes con una ileostomía o colostomía temporal tienen peores resultados funcionales a largo plazo, parece que la razón para crear un estoma temporal, más que el estoma en sí, se asocia a este fenómeno. El tiempo hasta la reversión de un estoma temporal no influye en los resultados funcionales. (Traducción-Dr. Jorge Silva Velazco ).

Inter-observer variability in library plan selection on iterative CBCT and synthetic CT images of cervical cancer patients.

INTRODUCTION: In the Library-of-Plans (LoP) approach, correct plan selection is essential for delivering radiotherapy treatment accurately. However, poor image quality of the cone-beam computed tomography (CBCT) may introduce inter-observer variability and thereby hamper accurate plan selection. In this study, we investigated whether new techniques to improve the CBCT image quality and improve consistency in plan selection, affects the accuracy of LoP selection in cervical cancer patients. MATERIALS AND METHODS: CBCT images of 12 patients were used to investigate the inter-observer variability of plan selection based on different CBCT image types. Six observers were asked to individually select a plan based on clinical X-ray Volumetric Imaging (XVI) CBCT, iterative reconstructed CBCT (iCBCT) and synthetic CTs (sCT). Selections were performed before and after a consensus meeting with the entire group, in which guidelines were created. A scoring by all observers on the image quality and plan selection procedure was also included. For plan selection, Fleiss' kappa (κ) statistical test was used to determine the inter-observer variability within one image type. RESULTS: The agreement between observers was significantly higher on sCT compared to CBCT. The consensus meeting improved the duration and inter-observer variability. In this manuscript, the guidelines attributed the overall results in the plan selection. Before the meeting, the gold standard was selected in 76% of the cases on XVI CBCT, 74% on iCBCT, and 76% on sCT. After the meeting, the gold standard was selected in 83% of the cases on XVI CBCT, 81% on iCBCT, and 90% on sCT. CONCLUSION: The use of sCTs can increase the agreement of plan selection among observers and the gold standard was indicated to be selected more often. It is important that clear guidelines for plan selection are implemented in order to benefit from the increased image quality, accurate selection, and decrease inter-observer variability.

Co-occurrence of fecal incontinence with constipation or irritable bowel syndrome indicates the need for personalized treatment.

BACKGROUND: This study aimed to compare the prevalence and symptoms of fecal incontinence (FI) in relation to irritable bowel syndrome (IBS-associated FI), constipation (constipation-associated FI), and isolation (isolated FI). METHODS: Data were analyzed from 3145 respondents without organic comorbidities known to influence defecation function from the general Chinese population who filled in the online Groningen Defecation and Fecal Continence questionnaire. FI, IBS, and constipation were evaluated with the Rome IV criteria. KEY RESULTS: The prevalence of FI was 10.5% (n = 329) in the non-comorbidity group. After multivariable logistic regression analysis, IBS (odds ratio [OR]: 12.55, 95% confidence interval [CI]: 9.06-17.36) and constipation (OR: 4.38, 95% CI: 3.27-5.85) were the most significant factors contributing to FI. Based on this finding, 106/329 (32.2%) had IBS-associated FI, 119/329 (36.2%) had constipation-associated FI, and 104/329 (31.6%) had isolated FI. Among the 329 FI respondents, there was a high prevalence of IBS and constipation-related symptoms, including abdominal pain (81.5%) and abdominal bloating (77.8%) for IBS and straining during defecation (75.4%), incomplete defecation (72.3%), defecation blockage (63.2%), anal pain during defecation (59.3%), and hard stools (24%) for constipation. The patients with IBS-associated FI asked for specialists' help less frequently than those with isolated FI. Interestingly, among the patients with constipation-associated FI, 56.3% used anti-diarrhea medicine. CONCLUSIONS AND INFERENCES: The prevalence of IBS-associated FI, constipation-associated FI, and isolated FI is comparably high. It is important to diagnose and target the cause of FI to provide personalized and cause-targeting care instead of treating only the FI symptoms.

Validation of the Chinese DeFeC questionnaire: a comprehensive screening tool for symptoms and causes of constipation and incontinence.

BACKGROUND: Currently, the diagnosis of defecation disorders in China is usually based on varied and ambiguous criteria. We aimed to translate the Groningen Defecation and Fecal Continence (DeFeC) questionnaire to Chinese and test its reproducibility and feasibility in the general Chinese population. METHODS: The Groningen Defecation Questionnaire was translated into Chinese according to the COnsensus-based Standards for the selection of health Measurement Instruments (COSMIN). The feasibility and reproducibility were evaluated by performing a test-retest online survey and calculating the Cohen's kappa (κ) coefficient [or intraclass correlation coefficient (ICC)], with 0.01-0.20 considered slight agreement; 0.21-0.40, fair agreement; 0.41-0.60, moderate agreement; 0.61-0.80, substantial agreement; and 0.81-1.00, almost perfect agreement. RESULTS: In total, 130 respondents completed the questionnaire twice, with a mean age of 47.08±12.46 years. No remarks were made that indicted that the questions were difficult to understand. The median time to complete the questionnaire was 20.78 min [interquartile range (IQR), 14.83-29.20 min] for the first time. The κ coefficient of all defecation function-related domains ranged between 0.25 and 0.71, with an average value of 0.53. The constipation and fecal incontinence-related domains showed a substantial and moderate agreement level, as indicated by κ of 0.65 and 0.52, respectively. The Agachan constipation score and Wexner incontinence score showed perfect and substantial agreement, as indicated by an ICC of 0.88 and 0.74, respectively. CONCLUSIONS: The Chinese version of the Groningen DeFeC questionnaire is highly feasible and reproducible and can be applied in clinical and research activities for the Chinese population.

The Prevalence of Bowel and Bladder Function During Early Childhood: A Population-Based Study.

OBJECTIVES: Our primary aim was to determine bowel and bladder function in children aged 1 month to 7 years in the general Dutch population. Second, we aimed to identify demographic factors associated with the presence of bowel and bladder dysfunction, and their coexistence. METHODS: For this cross-sectional, population-based study, parents/caregivers of children aged from 1 month to 7 years were asked to complete the Early Pediatric Groningen Defecation and Fecal Continence questionnaire. Different parameters of bowel and bladder function were assessed using validated scoring systems such as the Rome IV criteria. RESULTS: The mean age of the study population (N = 791) was 3.9 ± 2.2 years. The mean age at which parents/caregivers considered their child fully toilet-trained was 5.1 ± 1.5 years. Prevalence of fecal incontinence among toilet-trained children was 12%. Overall prevalence of constipation was 14%, with a constant probability and severity at all ages. We found significant associations between fecal incontinence and constipation [odds ratio (OR) = 3.88, 95% CI: 2.06-7.30], fecal incontinence and urinary incontinence (OR = 5.26, 95% CI: 2.78-9.98), and constipation and urinary incontinence (OR = 2.06, 95% CI: 1.24-3.42). CONCLUSIONS: Even though most children are fully toilet-trained at 5 years, fecal incontinence is common. Constipation appears to be common in infants, toddlers, and older children. Fecal incontinence and constipation frequently coexist and are often accompanied by urinary incontinence. Increased awareness of bowel and bladder dysfunction in infants, toddlers, and young children is required to prevent these problems from continuing at older ages.

Anatomical evaluation of deep-learning synthetic computed tomography images generated from male pelvis cone-beam computed tomography.

Background and purpose: To improve cone-beam computed tomography (CBCT), deep-learning (DL)-models are being explored to generate synthetic CTs (sCT). The sCT evaluation is mainly focused on image quality and CT number accuracy. However, correct representation of daily anatomy of the CBCT is also important for sCTs in adaptive radiotherapy. The aim of this study was to emphasize the importance of anatomical correctness by quantitatively assessing sCT scans generated from CBCT scans using different paired and unpaired dl-models. Materials and methods: Planning CTs (pCT) and CBCTs of 56 prostate cancer patients were included to generate sCTs. Three different dl-models, Dual-UNet, Single-UNet and Cycle-consistent Generative Adversarial Network (CycleGAN), were evaluated on image quality and anatomical correctness. The image quality was assessed using image metrics, such as Mean Absolute Error (MAE). The anatomical correctness between sCT and CBCT was quantified using organs-at-risk volumes and average surface distances (ASD). Results: MAE was 24 Hounsfield Unit (HU) [range:19-30 HU] for Dual-UNet, 40 HU [range:34-56 HU] for Single-UNet and 41HU [range:37-46 HU] for CycleGAN. Bladder ASD was 4.5 mm [range:1.6-12.3 mm] for Dual-UNet, 0.7 mm [range:0.4-1.2 mm] for Single-UNet and 0.9 mm [range:0.4-1.1 mm] CycleGAN. Conclusions: Although Dual-UNet performed best in standard image quality measures, such as MAE, the contour based anatomical feature comparison with the CBCT showed that Dual-UNet performed worst on anatomical comparison. This emphasizes the importance of adding anatomy based evaluation of sCTs generated by dl-models. For applications in the pelvic area, direct anatomical comparison with the CBCT may provide a useful method to assess the clinical applicability of dl-based sCT generation methods.

Long-Term Outcomes After Chemoradiotherapy and Surgery for Superior Sulcus Tumors.

Introduction: Superior sulcus tumors (SSTs) are uncommon, and their anatomical location can make treatment challenging. We analyzed late outcomes of patients with SST treated with concurrent chemoradiotherapy followed by surgical resection (trimodality) in a single tertiary institution. Methods: Patients with non-small cell SSTs, who underwent trimodality therapy between 2002 and 2017, were selected from a prospective institutional surgical database. Patients were uniformly staged with 18F-fluorodeoxyglucose-positron emission tomography, computed tomography scan of the chest and upper abdomen, and brain imaging. Patients undergoing resection of the lung plus chest wall were grouped as limited SST and those needing extensive resections (e.g., including the vertebral body) as extended SST. Kaplan-Meier survival analysis was performed to determine difference in survival. Multivariate Cox regression was used to identify prognostic factors. Results: A total of 123 patients were identified with a median follow-up of 4.9 years (interquartile range: 1.6-8.9 y). The 90-day postoperative mortality and morbidity (Clavien-Dindo grades III-V) were 6.5% and 21.1%, respectively. Patients with a radical resection (R0: 92.7%) had better survival (p = 0.002), as did those who had major pathologic response (73%) (p = 0.001). Ten-year overall survival (OS) and disease-free survival were 48.1% and 42.6%, respectively. There were no differences in 90-day mortality (p = 0.31) and OS (p = 0.79) between extended SST and limited SST patients. Conclusions: In patients with SST, trimodality resulted in a 10-year estimated OS and disease-free survival of 48.1% and 42.6%, respectively, which were improved after radical resection (R0) and major pathologic response. Survival for limited and extended resections was comparable, and distant relapse was the main pattern of failure. Better systemic treatments are therefore needed.

A possible physiological mechanism of rectocele formation in women.

BACKGROUND: We aimed to determine the anorectal physiological factors associated with rectocele formation. METHODS: Female patients (N = 32) with severe constipation, fecal incontinence, or suspicion of rectocele, who had undergone magnetic resonance defecography and anorectal function tests between 2015 and 2021, were retrospectively included for analysis. The anorectal function tests were used to measure pressure in the anorectum during defecation. Rectocele characteristics and pelvic floor anatomy were determined with magnetic resonance defecography. Constipation severity was determined with the Agachan score. Information regarding constipation-related symptoms was collected. RESULTS: Mean rectocele size during defecation was 2.14 ± 0.88 cm. During defecation, the mean anal sphincter pressure just before defecation was 123.70 ± 67.37 mm Hg and was associated with rectocele size (P = 0.041). The Agachan constipation score was moderately correlated with anal sphincter pressure just before defecation (r = 0.465, P = 0.022), but not with rectocele size (r = 0.276, P = 0.191). During defecation, increased anal sphincter pressure just before defecation correlated moderately and positively with straining maneuvers (r = 0.539, P = 0.007) and defecation blockage (r = 0.532, P = 0.007). Rectocele size correlated moderately and positively with the distance between the pubococcygeal line and perineum (r = 0.446, P = 0.011). CONCLUSION: Increased anal sphincter pressure just before defecation is correlated with the rectocele size. Based on these results, it seems important to first treat the increased anal canal pressure before considering surgical rectocele repair to enhance patient outcomes.

Anastomotic Height Is a Valuable Indicator of Long-term Bowel Function Following Surgery for Rectal Cancer.

BACKGROUND: The exact relation between anastomotic height after rectal cancer surgery and postoperative bowel function problems has not been investigated in the long term, resulting in ineffective treatment. OBJECTIVE: The goal of this study was to determine the effect of anastomotic height on long-term bowel function and generic quality of life. DESIGN: This was a multicenter, cross-sectional study. SETTINGS: Seven hospitals in the north of the Netherlands participated. PATIENTS: All patients who underwent rectal cancer surgery between 2009 and 2015 in participating hospitals received the validated Defecation and Fecal Continence and Short-Form 36 questionnaires. Deceased patients, patients with a permanent stoma or an anastomosis >15 cm from the anal verge, patients with intellectual disability, and patients living abroad were excluded. MAIN OUTCOME MEASURES: Primary outcomes were constipation (Rome IV), fecal incontinence (Rome IV), and major low anterior resection syndrome. Secondary outcomes were the generic quality of life scores. RESULTS: The study population ( n = 630) had a median follow-up of 58.0 months. In multivariable analysis, constipation (OR = 1.08; 95% CI, 1.02-1.15; p = 0.011), fecal incontinence (OR = 0.91; 95% CI, 0.84-0.97; p = 0.006), and major low anterior resection syndrome (OR = 0.93; 95% CI, 0.87-0.99; p = 0.027), were significantly associated with anastomotic height. The curves illustrating the probability of constipation and fecal incontinence crossed at an anastomotic height of 7 cm, with 95% CIs overlapping between 4.5 and 9.5 cm. There was no relation between quality-of-life scores and anastomotic height. LIMITATIONS: The study is limited by its cross-sectional design. CONCLUSIONS: This study might serve as a guide for the clinician to effectively screen and treat fecal incontinence and constipation during patient follow-up after rectal cancer surgery. More attention should be paid to fecal incontinence in patients with an anastomosis below 4.5 cm and toward constipation in patients with an anastomosis above 9.5 cm. See Video Abstract at http://links.lww.com/DCR/B858 . LA ALTURA ANASTOMTICA ES UN INDICADOR VALIOSO DE LA FUNCIN INTESTINAL A LARGO PLAZO DESPUS DE LA CIRUGA PARA EL CNCER DE RECTO: ANTECEDENTES:La relación exacta entre la altura anastomótica después de la cirugía de cáncer de recto y los problemas posoperatorios de la función intestinal no se ha investigado a largo plazo, lo que causa un tratamiento ineficaz.OBJETIVO:Determinar el efecto de la altura anastomótica sobre la función intestinal a largo plazo y la calidad de vida genérica.DISEÑO:Estudio multicéntrico transversal.DISEÑO DEL ESTUDIO:Participaron siete hospitales holandeses en el norte de los Países Bajos.PACIENTES:Todos los pacientes que se sometieron a cirugía de cáncer de recto entre 2009 y 2015 en los hospitales participantes recibieron los cuestionarios validados de Defecación y Continencia Fecal y Short-Form 36. Se excluyeron pacientes fallecidos, pacientes con estoma permanente o anastomosis > 15 cm del borde anal, discapacidad intelectual o residentes en el extranjero.PRINCIPALES MEDIDAS DE RESULTADO:Los resultados primarios fueron estreñimiento (Roma IV), incontinencia fecal (Roma IV) y síndrome de resección anterior baja mayor. Los resultados secundarios fueron las puntuaciones genéricas de calidad de vida.RESULTADOS:La población de estudio (N = 630) tuvo una mediana de seguimiento de 58.0 meses. En el análisis multivariable el estreñimiento (OR = 1,08, IC del 95%, 1,02-1,15, p = 0,011), incontinencia fecal (OR = 0,91, IC del 95%, 0,84-0,97, p = 0,006) y síndrome de resección anterior baja mayor (OR = 0,93, IC del 95%, 0,87-0,99, p = 0,027) se asociaron significativamente con la altura anastomótica. Las curvas que ilustran la probabilidad de estreñimiento e incontinencia fecal se cruzaron a una altura anastomótica de 7 cm, con IC del 95% superpuestos entre 4,5 y 9,5 cm. No hubo relación entre las puntuaciones de calidad de vida y la altura anastomótica.LIMITACIONES:El estudio está limitado por su diseño transversal.CONCLUSIONES:Este estudio podría servir como una guía para que el médico evalúe y trate eficazmente la incontinencia fecal y el estreñimiento durante el seguimiento de los pacientes después de la cirugía de cáncer de recto. Se debe prestar más atención a la incontinencia fecal en pacientes con anastomosis por debajo de 4,5 cm y al estreñimiento en pacientes con anastomosis por encima de 9,5 cm. Consulte Video Resumen en http://links.lww.com/DCR/B858 . (Traducción-Dr. Yazmin Berrones-Medina ).

Diagnosing Mild Forms of Anorectal Malformation With Anorectal Manometry: A Prospective Study.

INTRODUCTION: Rectoperineal congenital anorectal malformations (CARMs) are diagnosed by examining the perineum, combined with electric stimulation (ES) of the anal sphincter performed under anesthesia. This procedure may be troublesome because it is based on the observed contractibility of the sphincter. We aimed to add 3-dimensional high-resolution anorectal manometry (3D-HRAM) to the procedure and to assess its value for diagnosing rectoperineal forms of CARM. METHODS: We prospectively included 66 patients younger than 24 months who presented with constipation and were suspected of CARM, idiopathic constipation, or Hirschsprung disease. The patients were assessed between 2015 and 2021 at University Medical Center Groningen, the Netherlands. All patients underwent 3D-HRAM, followed by the standard diagnostic procedure for either CARM or Hirschsprung disease. RESULTS: Of the 51 patients who underwent both 3D-HRAM and ES, we observed that patients with rectoperineal CARM revealed a pressure gap along the anterior part of the anal sphincter. Based on this observation, we diagnosed 35 patients with CARM. Subsequently, all 35 diagnoses were confirmed with ES. Sixteen patients were diagnosed as not having CARM, 100% of whom were in agreement with the gold standard-ES. Both the specificity and sensitivity of 3D-HRAM for diagnosing rectoperineal CARM were 100%. DISCUSSION: We consider 3D-HRAM a reliable tool for diagnosing and excluding rectoperineal CARM. Using this method in patients suspected of CARM might keep infants from undergoing unnecessary interventions requiring anesthetics, such as ES. By providing objective insight into the functional capabilities of the anal sphincter, anorectal manometry adds to the diagnosis.

Development and validation of the Early Pediatric Groningen Defecation and Fecal Continence questionnaire.

There are no compatible tools that assess bowel function in young children, older children, and adults. This precludes clinical follow-up and longitudinal scientific research. Our aim was therefore to develop and validate a bowel function questionnaire equivalent to the pediatric (8-17 years) and adult (≥ 18 years) Groningen Defecation and Fecal Continence (DeFeC) questionnaires for children from the age of 1 month to 7 years. We developed, validated, and translated the Early Pediatric Groningen DeFeC (EP-DeFeC) questionnaire according to the Consensus-based Standards for the selection of health Measurement Instruments (COSMIN). The EP-DeFeC incorporates different validated bowel function scoring systems, including the Rome IV criteria that are also included in the pediatric and adult DeFeC. We assessed feasibility and reproducibility by a test-retest survey. The study population (N = 100) consisted of the parents/caregivers of children whose median age was 4.0 (IQR 2.0-5.0) years. The mean interval between testing and retesting was 2.7 ± 1.1 months. None of the respondents commented on ambiguities regarding the questions. The overall median time taken to complete the EP-DeFeC was 8.7 min (IQR 6.8-11.8). The overall observed agreement was 78.9% with an overall kappa coefficient of 0.51, indicating moderate agreement. CONCLUSION: The EP-DeFeC is a feasible, reproducible, and validated questionnaire for assessing bowel function in children from the age of 1 month to 7 years. If used in combination with its pediatric (8-17 years) and adult (≥ 18 years) equivalents, this questionnaire enables longitudinal follow-up of bowel function from infancy to adulthood. WHAT IS KNOWN: • Bowel function problems are common among young children. • Unfortunately, there are no compatible tools that assess bowel function in young children, older children, and adults, which precludes clinical follow-up and longitudinal scientific research. WHAT IS NEW: • The Early Pediatric Groningen Defecation and Fecal Continence (EP-DeFeC) questionnaire is validated to assess bowel function in children from the age of 1 month to 7 years. • If used together with its pediatric and adult equivalents, longitudinal follow-up of bowel function from infancy to adulthood becomes possible.