Longitudinal associations of plasma kynurenines and ratios with fatigue and quality of life in colorectal cancer survivors up to 12 months post-treatment.

Fatigue is prevalent in colorectal cancer (CRC) survivors, impacting their health-related quality of life (HRQoL). Inflammation-induced activation of the kynurenine pathway may play a role in cancer-related fatigue and HRQoL, but evidence is scarce. Therefore, we aimed to investigate longitudinal associations of plasma tryptophan, kynurenines, and ratios with fatigue and HRQoL in CRC survivors up to 12 months post-treatment. Repeated measurements at 6 weeks, 6 months, and 12 months post-treatment were performed in 249 stage I-III CRC survivors. Plasma tryptophan and eight kynurenines were analyzed using liquid chromatography-tandem mass spectrometry (LC/MS-MS). Fatigue and HRQoL outcomes were evaluated using validated questionnaires. Confounder-adjusted linear mixed models were conducted to analyze longitudinal associations, with false discovery rate (FDR) correction. Higher tryptophan (Trp), kynurenic acid (KA), and xanthurenic acid (XA) concentrations, as well as a higher kynurenic acid-to-quinolinic acid ratio (KA/QA), were associated with less fatigue and better functioning, while a higher kynurenine-to-tryptophan ratio (KTR) and 3-hydroxykynurenine ratio (HKr) were associated with more fatigue and worse functioning. Finally, higher KA and XA concentrations and a higher KA/QA ratio were associated with a higher overall HRQoL summary score, while a higher HKr was associated with a lower overall HRQoL summary score. In conclusion, we observed that tryptophan and several kynurenines were longitudinally associated with fatigue and HRQoL in CRC survivors up to 12 months post-treatment. Future research is needed to validate our findings and explore the potential of the kynurenine pathway as intervention target for reducing fatigue and enhancing HRQoL after CRC treatment.

Sacral Neuromodulation Versus Conservative Treatment for Refractory Idiopathic Slow-transit Constipation: The Randomized Clinical No.2-Trial.

OBJECTIVE: Assess the effectiveness of sacral neuromodulation (SNM) versus personalized conservative treatment (PCT) in patients with refractory idiopathic slow-transit constipation (STC). BACKGROUND: Evidence on SNM for idiopathic STC is conflicting and of suboptimal methodological quality. METHODS: The No.2-Trial was a multicenter, open-label, pragmatic, randomized trial performed in 2 Dutch hospitals. Sixty-seven patients with idiopathic STC, a defecation frequency <3 per week and refractory (ie, unresponsive) to maximal conservative (nonoperative) treatment were included. Exclusion criteria included outlet obstruction, rectal prolapse, and previous colon surgery. Patients were randomized (3:2) to SNM (n=41) or PCT (n=26) with randomization minimization between February 21, 2017 and March 12, 2020. In SNM patients, an implantable pulse generator was implanted after a successful 4-week test stimulation. PCT patients received conservative treatment such as laxatives or retrograde colonic irrigation. The primary outcome was treatment success (defined as average defecation frequency ≥3 per week) after 6 months. Secondary outcomes included constipation severity, fatigue, quality of life, and adverse events. Analysis was according to intention-to-treat. RESULTS: After 6 months, 22 (53.7%) patients were successfully treated with SNM versus 1 (3.8%) patient with PCT (odds ratio 36.4, 95% CI 3.4-387.5, P =0.003). At 6 months, SNM patients reported lower constipation severity and fatigue scores ( P <0.001) and improved quality of life compared with PCT ( P <0.001). Eight serious adverse events (6 SNM, 2 PCT) and 78 adverse events (68 SNM, 10 PCT) were reported. CONCLUSIONS: SNM is a promising surgical treatment option in a homogeneous group of adults and adolescents with refractory idiopathic STC. No.2-Trial registered at ClinicalTrials.gov NCT02961582.

Longitudinal associations of diurnal rest-activity rhythms with fatigue, insomnia, and health-related quality of life in survivors of colorectal cancer up to 5 years post-treatment.

BACKGROUND: There is a growing population of survivors of colorectal cancer (CRC). Fatigue and insomnia are common symptoms after CRC, negatively influencing health-related quality of life (HRQoL). Besides increasing physical activity and decreasing sedentary behavior, the timing and patterns of physical activity and rest over the 24-h day (i.e. diurnal rest-activity rhythms) could also play a role in alleviating these symptoms and improving HRQoL. We investigated longitudinal associations of the diurnal rest-activity rhythm (RAR) with fatigue, insomnia, and HRQoL in survivors of CRC. METHODS: In a prospective cohort study among survivors of stage I-III CRC, 5 repeated measurements were performed from 6 weeks up to 5 years post-treatment. Parameters of RAR, including mesor, amplitude, acrophase, circadian quotient, dichotomy index, and 24-h autocorrelation coefficient, were assessed by a custom MATLAB program using data from tri-axial accelerometers worn on the upper thigh for 7 consecutive days. Fatigue, insomnia, and HRQoL were measured by validated questionnaires. Confounder-adjusted linear mixed models were applied to analyze longitudinal associations of RAR with fatigue, insomnia, and HRQoL from 6 weeks until 5 years post-treatment. Additionally, intra-individual and inter-individual associations over time were separated. RESULTS: Data were available from 289 survivors of CRC. All RAR parameters except for 24-h autocorrelation increased from 6 weeks to 6 months post-treatment, after which they remained relatively stable. A higher mesor, amplitude, circadian quotient, dichotomy index, and 24-h autocorrelation were statistically significantly associated with less fatigue and better HRQoL over time. A higher amplitude and circadian quotient were associated with lower insomnia. Most of these associations appeared driven by both within-person changes over time and between-person differences in RAR parameters. No significant associations were observed for acrophase. CONCLUSIONS: In the first five years after CRC treatment, adhering to a generally more active (mesor) and consistent (24-h autocorrelation) RAR, with a pronounced peak activity (amplitude) and a marked difference between daytime and nighttime activity (dichotomy index) was found to be associated with lower fatigue, lower insomnia, and a better HRQoL. Future intervention studies are needed to investigate if restoring RAR among survivors of CRC could help to alleviate symptoms of fatigue and insomnia while enhancing their HRQoL. TRIAL REGISTRATION: EnCoRe study NL6904 ( https://www.onderzoekmetmensen.nl/ ).

Impact of Anastomotic Leakage After Colorectal Cancer Surgery on Quality of Life: A Systematic Review.

BACKGROUND: Colorectal anastomotic leakage remains one of the most frequent and dreaded postoperative complications following colorectal resection. However, limited research has been conducted on the impact of this complication on quality of life of patients undergoing colorectal cancer surgery. OBJECTIVE: The aim of this systematic review was to identify, appraise and synthesize the available evidence regarding quality of life in patients with anastomotic leakage following oncological colorectal resections in order to inform clinical decision-making. DATA SOURCES AND STUDY SELECTION: PubMed, Embase, and the Cochrane library were searched for studies reporting on quality of life using validated questionnaires in patients with anastomotic leakage after oncological colorectal resections. The literature search was performed systematically and according to PRISMA guidelines. OUTCOMES: Outcomes of quality of life questionnaire scores of patients with and without anastomotic leakage were analyzed. RESULTS: Thirteen articles reporting on 4618 individual patients were included, among which 527 patients developed anastomotic leakage. Quality of life was evaluated utilizing ten distinct questionnaires administered at various postoperative time points, ranging from 1 month to 14 years. Quality of life outcomes differed across studies and timepoints, but overall scores were most negatively affected by anastomotic leakage up to 12 months postoperatively. LIMITATIONS: There was a high heterogeneity between the included studies based on used questionnaires and time of assessment. CONCLUSION: The published evidence suggests that anastomotic leakage following oncologic colorectal resection is associated with impaired quality of life, especially within the first postoperative year. The impact of anastomotic leakage on quality of life warrants further evaluation and discussion with patients.

Longitudinal associations of circadian eating patterns with sleep quality, fatigue and inflammation in colorectal cancer survivors up to 24 months post-treatment.

Fatigue and insomnia, potentially induced by inflammation, are distressing symptoms experienced by colorectal cancer (CRC) survivors. Emerging evidence suggests that besides the nutritional quality and quantity, also the timing, frequency and regularity of dietary intake (chrono-nutrition) could be important for alleviating these symptoms. We investigated longitudinal associations of circadian eating patterns with sleep quality, fatigue and inflammation in CRC survivors. In a prospective cohort of 459 stage I-III CRC survivors, four repeated measurements were performed between 6 weeks and 24 months post-treatment. Chrono-nutrition variables included meal energy contribution, frequency (a maximum of six meals could be reported each day), irregularity and time window (TW) of energetic intake, operationalised based on 7-d dietary records. Outcomes included sleep quality, fatigue and plasma concentrations of inflammatory markers. Longitudinal associations of chrono-nutrition variables with outcomes from 6 weeks until 24 months post-treatment were analysed by confounder-adjusted linear mixed models, including hybrid models to disentangle intra-individual changes from inter-individual differences over time. An hour longer TW of energetic intake between individuals was associated with less fatigue (ß: -6·1; 95 % CI (-8·8, -3·3)) and insomnia (ß: -4·8; 95 % CI (-7·4, -2·1)). A higher meal frequency of on average 0·6 meals/d between individuals was associated with less fatigue (ß: -3·7; 95 % CI (-6·6, -0·8)). An hour increase in TW of energetic intake within individuals was associated with less insomnia (ß: -3·0; 95 % CI (-5·2, -0·8)) and inflammation (ß: -0·1; 95 % CI (-0·1, 0·0)). Our results suggest that longer TWs of energetic intake and higher meal frequencies may be associated with less fatigue, insomnia and inflammation among CRC survivors. Future studies with larger contrasts in chrono-nutrition variables are needed to confirm these findings.

Toward a core outcome set for faecal incontinence-A systematic review of outcomes reported in the literature.

AIM: Faecal incontinence (FI) is a prevalent issue which can have a detrimental impact on the patient's quality of life. Current international guidelines lack strong treatment recommendations due to few studies in the field, in combination with the heterogeneity in outcome reporting. To address this, a core outcome set (COS) is proposed to standardize outcome reporting in FI studies, facilitating meta-analyses and enhancing therapeutic recommendations. Through several steps outlined by COMET 'what' to measure will be determined prior to determining 'how' to measure these outcomes. This systematic review aims to identify 'what' outcomes have been used in FI intervention studies so far in adult patients as a starting phase for the development of a future COS for FI. METHOD: Medline, Embase and the Cochrane library were searched to identify all outcomes reported in comparative effectiveness trials assessing one or more treatment option in adult patients suffering from FI. The outcomes were categorized according to the Core Outcome Measurement in Effectiveness Trials (COMET) taxonomy to standardize outcome terminology, assess completeness, and inform subsequent steps in COS development. RESULTS: A total of 109 studies were included, which revealed 51 unique outcomes classified into 38 domains within four core areas. On average four outcomes were reported per study (range 1-11). The most commonly reported outcomes were "severity of FI" (83%), "quality of life" (64%), "number of FI episodes" (40%), "anorectal motor function" (39%), and "frequency of bowel movements" (16%). CONCLUSION: This systematic review offers an overview of outcomes reported in FI studies, highlighting the heterogeneity between studies. This heterogeneity emphasizes the need for standardizing outcome reporting which can be established through the creation of a COS.

Effectiveness, safety and cost-effectiveness of sacral neuromodulation for idiopathic slow-transit constipation: a systematic review.

AIM: Sacral neuromodulation (SNM) is a minimally invasive treatment option for functional constipation. Evidence regarding its effectiveness is contradictory, driven by heterogeneous study populations and designs. The aim of this study was to assess the effectiveness, safety and cost-effectiveness of SNM in children and adults with refractory idiopathic slow-transit constipation (STC). METHOD: OVID Medline, OVID Embase, Cochrane Library, the KSR Evidence Database, the NHS Economic Evaluation Database and the International HTA Database were searched up to 25 May 2023. For effectiveness outcomes, randomized controlled trials (RCTs) were selected. For safety outcomes, all study designs were selected. For cost-effectiveness outcomes, trial- and model-based economic evaluations were selected for review. Study selection, risk of bias and quality assessment, and data extraction were independently performed by two reviewers. For the intervention 'sacral neuromodulation' effectiveness outcomes included defaecation frequency and constipation severity. Safety and cost-effectiveness outcomes were, respectively, adverse events and incremental cost-effectiveness ratios. RESULTS: Of 1390 records reviewed, 67 studies were selected for full-text screening. For effectiveness, one cross-over and one parallel-group RCT was included, showing contradictory results. Eleven studies on safety were included (four RCTs, three prospective cohort studies and four retrospective cohort studies). Overall infection rates varied between 0% and 22%, whereas reoperation rates varied between 0% and 29%. One trial-based economic evaluation was included, which concluded that SNM was not cost-effective compared with personalized conservative treatment at a time horizon of 6 months. The review findings are limited by the small number of available studies and the heterogeneity in terms of study populations, definitions of refractory idiopathic STC and study designs. CONCLUSION: Evidence for the (cost-)effectiveness of SNM in children and adults with refractory idiopathic STC is inconclusive. Reoperation rates of up to 29% were reported.

Quality of life and functional outcome of rectal cancer patients: A prospective cohort study.

AIM: In the last decade, the Netherlands has implemented various diagnostic and treatment strategies to enhance rectal cancer outcomes. This study, using data from the Prospective Dutch ColoRectal Cancer (PLCRC) cohort, investigates whether these multidisciplinary advancements have translated into improved health-related quality of life (HRQoL) and functional outcomes for the general Dutch rectal cancer population. METHODS: Patients with Stage I-III rectal cancer enrolled in the PLCRC cohort were included. HRQoL and functional outcomes were assessed 1 and 2 years after diagnosis using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30), EORTC QLQ Colorectal Cancer 29 and the Low Anterior Resection Syndrome score. HRQoL and functional outcomes were compared based on year of diagnosis (2014-2019). RESULTS: A total of 1294 patients were included. Two years after diagnosis, patients diagnosed in 2019 (n = 392) had a clinically relevant higher score on physical (8.2, 95% CI 4.1-12.3), role (13.5, 95% CI 7.3-19.7) and social functioning (5.8, 95% CI 0.3-11.2) compared to those diagnosed in 2014 (n = 65). Additionally, patients diagnosed in 2019 experienced less fatigue 2 years after diagnosis compared to those diagnosed in 2014 (-8.6, 95% CI -14.1 to -3.0). The Low Anterior Resection Syndrome score showed no differences. CONCLUSION: The findings of this study suggest that over the past decade rectal cancer patients in the Netherlands have witnessed improvements in HRQoL across various domains. Most probably, the improvement is due to a combination of implementation of population screening, a more restrictive neoadjuvant radiotherapy policy and advances in minimally invasive surgery and organ preserving treatment options.

European Society of Coloproctology: Guidelines for diagnosis and treatment of cryptoglandular anal fistula.

AIM: The primary aim of the European Society of Coloproctology (ESCP) Guideline Development Group (GDG) was to produce high-quality, evidence-based guidelines for the management of cryptoglandular anal fistula with input from a multidisciplinary group and using transparent, reproducible methodology. METHODS: Previously published methodology in guideline development by the ESCP has been replicated in this project. The guideline development process followed the requirements of the AGREE-S tool kit. Six phases can be identified in the methodology. Phase one sets the scope of the guideline, which addresses the diagnostic and therapeutic management of perianal abscess and cryptoglandular anal fistula in adult patients presenting to secondary care. The target population for this guideline are healthcare practitioners in secondary care and patients interested in understanding the clinical evidence available for various surgical interventions for anal fistula. Phase two involved formulation of the GDG. The GDG consisted of 21 coloproctologists, three research fellows, a radiologist and a methodologist. Stakeholders were chosen for their clinical and academic involvement in the management of anal fistula as well as being representative of the geographical variation among the ESCP membership. Five patients were recruited from patient groups to review the draft guideline. These patients attended two virtual meetings to discuss the evidence and suggest amendments. In phase three, patient/population, intervention, comparison and outcomes questions were formulated by the GDG. The GDG ratified 250 questions and chose 45 for inclusion in the guideline. In phase four, critical and important outcomes were confirmed for inclusion. Important outcomes were pain and wound healing. Critical outcomes were fistula healing, fistula recurrence and incontinence. These outcomes formed part of the inclusion criteria for the literature search. In phase five, a literature search was performed of MEDLINE (Ovid), PubMed, Embase (Ovid) and the Cochrane Database of Systematic Reviews by eight teams of the GDG. Data were extracted and submitted for review by the GDG in a draft guideline. The most recent systematic reviews were prioritized for inclusion. Studies published since the most recent systematic review were included in our analysis by conducting a new meta-analysis using Review manager. In phase six, recommendations were formulated, using grading of recommendations, assessment, development, and evaluations, in three virtual meetings of the GDG. RESULTS: In seven sections covering the diagnostic and therapeutic management of perianal abscess and cryptoglandular anal fistula, there are 42 recommendations. CONCLUSION: This is an up-to-date international guideline on the management of cryptoglandular anal fistula using methodology prescribed by the AGREE enterprise.

The value of C-reactive protein, leucocytes and vital signs in detecting major complications after oncological colorectal surgery.

PURPOSE: To assess the association of postoperative C-reactive protein (CRP), leucocytes and vital signs in the first three postoperative days (PODs) with major complications after oncological colorectal resections in a tertiary referral centre for colorectal cancer in The Netherlands. METHODS: A retrospective cohort study, including 594 consecutive patients who underwent an oncological colorectal resection at Maastricht University Medical Centre between January 2016 and December 2020. Descriptive analyses of patient characteristics were performed. Logistic regression models were used to assess associations of leucocytes, CRP and Modified Early Warning Score (MEWS) at PODs 1-3 with major complications. Receiver operating characteristic curve analyses were used to establish cut-off values for CRP. RESULTS: A total of 364 (61.3%) patients have recovered without any postoperative complications, 134 (22.6%) patients have encountered minor complications and 96 (16.2%) developed major complications. CRP levels reached their peak on POD 2, with a mean value of 155 mg/L. This peak was significantly higher in patients with more advanced stages of disease and patients undergoing open procedures, regardless of complications. A cut-off value of 170 mg/L was established for CRP on POD 2 and 152 mg/L on POD 3. Leucocytes and MEWS also demonstrated a peak on POD 2 for patients with major complications. CONCLUSIONS: Statistically significant associations were found for CRP, Δ CRP, Δ leucocytes and MEWS with major complications on POD 2. Patients with CRP levels ≥ 170 mg/L on POD 2 should be carefully evaluated, as this may indicate an increased risk of developing major complications.

Longitudinal associations of plasma metabolites with persistent fatigue among colorectal cancer survivors up to 2 years after treatment.

The underlying biological mechanisms causing persistent fatigue complaints after colorectal cancer treatment need further investigation. We investigated longitudinal associations of circulating concentrations of 138 metabolites with total fatigue and subdomains of fatigue between 6 weeks and 2 years after colorectal cancer treatment. Among stage I-III colorectal cancer survivors (n = 252), blood samples were obtained at 6 weeks, and 6, 12 and 24 months posttreatment. Total fatigue and fatigue subdomains were measured using a validated questionnaire. Tandem mass spectrometry was applied to measure metabolite concentrations (BIOCRATES AbsoluteIDQp180 kit). Confounder-adjusted longitudinal associations were analyzed using linear mixed models, with false discovery rate (FDR) correction. We assessed interindividual (between-participant differences) and intraindividual longitudinal associations (within-participant changes over time). In the overall longitudinal analysis, statistically significant associations were observed for 12, 32, 17 and three metabolites with total fatigue and the subscales "fatigue severity," "reduced motivation" and "reduced activity," respectively. Specifically, higher concentrations of several amino acids, lysophosphatidylcholines, diacylphosphatidylcholines, acyl-alkylphosphatidylcholines and sphingomyelins were associated with less fatigue, while higher concentrations of acylcarnitines were associated with more fatigue. For "fatigue severity," associations appeared mainly driven by intraindividual associations, while for "reduced motivation" stronger interindividual associations were found. We observed longitudinal associations of several metabolites with total fatigue and fatigue subscales, and that intraindividual changes in metabolites over time were associated with fatigue severity. These findings point toward inflammation and an impaired energy metabolism due to mitochondrial dysfunction as underlying mechanisms. Mechanistic studies are necessary to determine whether these metabolites could be targets for intervention.

Longitudinal associations of fast foods, red and processed meat, alcohol and sugar-sweetened drinks with quality of life and symptoms in colorectal cancer survivors up to 24 months post-treatment.

Unhealthy dietary habits can contribute to the development of colorectal cancer (CRC). Such habits may also be associated with post-treatment symptoms experienced by CRC survivors. Therefore, we aimed to assess longitudinal associations of post-treatment unhealthy dietary habits, i.e. intake of ultra-processed foods (UPF), red and processed meat, alcohol and sugar-sweetened drinks, with health-related quality of life (HRQoL), fatigue and chemotherapy-induced peripheral neuropathy (CIPN) in CRC survivors from 6 weeks up to 24 months post-treatment. In a prospective cohort among stage I-III CRC survivors (n 396), five repeated home visits from diagnosis up to 24 months post-treatment were executed. Dietary intake was measured by 7-d dietary records to quantify consumption of UPF, red and processed meat, alcohol and sugar-sweetened drinks. HRQoL, fatigue and CIPN were measured by validated questionnaires. We applied confounder-adjusted linear mixed models to analyse longitudinal associations from 6 weeks until 24 months post-treatment. We applied a post hoc time-lag analysis for alcohol to explore the directionality. Results showed that higher post-treatment intake of UPF and sugar-sweetened drinks was longitudinally associated with worsened HRQoL and more fatigue, while higher intake of UPF and processed meat was associated with increased CIPN symptoms. In contrast, post-treatment increases in alcohol intake were longitudinally associated with better HRQoL and less fatigue; however, time-lag analysis attenuated these associations. In conclusion, unhealthy dietary habits are longitudinally associated with lower HRQoL and more symptoms, except for alcohol. Results from time-lag analysis suggest no biological effect of alcohol; hence, the longitudinal association for alcohol should be interpreted with caution.

Replacement Adaptor 09106 for patients with a dynamic graciloplasty or patients with sacral neuromodulation and abdominal implantable pulse generators: a retrospective, single centre, Stage 2a/2b development IDEAL case series.

AIM: Due to the introduction of a new implantable pulse generator (IPG), the Interstim II, patients with either a dynamic graciloplasty or an abdominally placed IPG for sacral neuromodulation could not undergo surgery to replace their IPG in the case of end of battery life. For these patients, the Medtronic Replacement Adaptor 09106 was created. This retrospective case series aims to study safety and feasibility of the Medtronic Replacement Adaptor 09106 in patients with abdominally placed IPGs. METHODS: Seventeen patients (11 women, six men) received a replacement adaptor with a follow-up of 6 months. Outcome measures consisted of a bowel habit diary. Adverse events were classified using the Clavien-Dindo classification. RESULTS: Outcome measures in the bowel habit diaries after replacement (feasibility) did not differ significantly from outcome measures before replacement. Adverse events occurred in four out of 17 patients (24%): two patients initially showed pocket site pain (Clavien-Dindo Grade I), which resolved without intervention. One patient suffered from poor wound closure (Clavien-Dindo Grade II) and one patient had persisting pocket pain (Clavien-Dindo Grade IIIa) for which a pocket revision was performed. Statistical analyses were performed making paired comparisons using a Wilcoxon signed rank test. CONCLUSION: The Medtronic Replacement Adaptor 09106 is a valuable option for patients with dynamic graciloplasty or sacral neuromodulation and abdominal IPG and has complication rates similar to replacement of the Interstim without Replacement Adaptor 09106.

English translation and cross-cultural validation of the patient-reported outcome measurement-haemorrhoidal impact and satisfaction score (PROM-HISS).

AIM: The aim of this study was to translate the Dutch patient-reported outcome measure-haemorrhoidal impact and satisfaction score (PROM-HISS) to English and perform a cross-cultural validation. METHOD: The ISPOR good practice guidelines for the cross-cultural validation of PROMs were followed and included two steps: (1) Two forward and two backward translations. The forward translation concerned the translation from the source language (Dutch) to the target language (English), performed by two independent English speakers, one medical doctor and one nonmedical. Subsequently, a discussion about discrepancies in the reconciled version was performed by a stakeholder group. (2) Cognitive interviews were held with patients with haemorrhoidal disease (HD), probing the comprehensibility and comprehensiveness of the PROM-HISS. RESULTS: Discrepancies in the reconciled forward translation concerned the terminology of HD symptoms. Furthermore, special attention was paid to the response options, ranging from "not at all", indicating minor symptoms, to "a lot", implying many symptoms. Consensus among the stakeholder group about the final version of the translated PROM-HISS was reached. Interviews were conducted with 10 native English-speaking HD patients (30% female), with a mean age of 44 years (24-83) and primarily diagnosed with grade II HD (80%). The mean time to complete the PROM-HISS was 1 min 43 s. Patients showed a good understanding of the questions and response options, found all items relevant and did not miss important symptoms or topics. CONCLUSION: The translated English language PROM-HISS is a valid tool to assess symptoms of HD, its impact on daily activities and patient satisfaction with HD treatment.

Responsiveness of the Patient-Reported Outcome Measure-Haemorrhoidal Impact and Satisfaction Score in patients with haemorrhoidal disease.

AIM: In this study we aimed to assess the responsiveness of the symptom score of the recently developed Patient-Reported Outcome Measure-Haemorrhoidal Impact and Satisfaction Score (PROM-HISS). Furthermore, the minimally relevant difference (MRD) was determined. METHOD: The responsiveness of PROM-HISS was tested using a criterion-based (i.e. anchor) and construct-based (i.e. hypotheses testing) approach. Patients with haemorrhoidal disease (HD) completed the PROM-HISS before and 1 week after treatment in hospital. A global self-assessment of change question (SCQ) was administered 1-week after treatment and functioned as the criterion. The following analyses were performed: (1) correlation between the PROM-HISS symptom score and the criterion (SCQ) and (2) hypotheses testing. The MRD was determined as change in symptoms of the subgroup reporting 'somewhat fewer complaints' on the SCQ. RESULTS: Between February and August 2022, 94 patients with grade II-IV HD from three hospitals were included. The correlation between the SCQ and a change on the PROM-HISS symptom score was 0.595 indicating that an improvement on the SCQ corresponds to an improvement on the PROM-HISS symptom score. As hypothesized, the mean change in PROM-HISS scores was significantly different between subgroups of patients based on their SCQ responses. Patients reporting a small change in HD symptoms on the SCQ corresponded to a mean change of 0.3 on the PROM-HISS symptom score. CONCLUSION: The PROM-HISS symptom score is a responsive instrument as it identifies change in HD symptoms because of treatment. The estimated MRD of 0.3 can be used to inform clinical research and practice.

Development of a standard set of PROs and generic PROMs for Dutch medical specialist care : Recommendations from the Outcome-Based Healthcare Program Working Group Generic PROMs.

PURPOSE: The added value of measuring patient-reported outcomes (PROs) for delivering patient-centered care and assessment of healthcare quality is increasingly evident. However, healthcare system wide data collection initiatives are hampered by the proliferation of patient-reported outcome measures (PROMs) and conflicting data collection standards. As part of a national initiative of the Dutch Ministry of Health, Welfare and Sport we developed a consensus-based standard set of generic PROs and PROMs to be implemented across Dutch medical specialist care. METHODS: A working group of mandated representatives of umbrella organizations involved in Dutch medical specialist care, together with PROM experts and patient organizations worked through a structured, consensus-driven co-creation process. This included literature reviews, online expert and working group meetings, and feedback from national patient- and umbrella organizations. The 'PROM-cycle' methodology was used to select feasible, valid, and reliable PROMs to obtain domain scores for each of the PROs included in the set. RESULTS: Eight PROs across different domains of health were ultimately endorsed: symptoms (pain & fatigue), functioning (physical, social/participation, mental [anxiety & depression]), and overarching (quality of life & perceived overall health). A limited number of generic PROMs was endorsed. PROMIS short forms were selected as the preferred instruments for all PROs. Several recommendations were formulated to facilitate healthcare system level adoption and implementation of the standard set. CONCLUSIONS: We developed a consensus-based standard set of Generic PROMs and a set of recommendations to facilitate healthcare system wide implementation across Dutch medical specialist care.

Sensory brain activation during rectal balloon distention: a pilot study in healthy volunteers to assess safety and feasibility at 1.5T.

OBJECTIVE: Although increasing evidence suggests a central mechanism of action for sacral neuromodulation, the exact mechanism remains unclear. We set up a scanning paradigm to measure brain activation related to various stages of rectal filling using rectal balloon distention. MATERIALS AND METHODS: Six healthy volunteers underwent rectal balloon distention during MRI scanning at a 1.5T scanner with a Tx/Rx head coil. MR images were collected at four levels of distention: empty balloon (EB), first sensation volume (FSV), desire to defecate volume (DDV), maximum tolerable volume (MTV). Data were analyzed using BrainVoyager 20.4. Whole brain and ROI-based fixed-effects general linear model analyses were performed on the fMRI time-course data from all participants. RESULTS: Rectal filling until FSV evoked the most blood-oxygen-level-dependent responses in several clusters throughout the cortex, followed by the responses evoked by rectal filling until DDV. Interestingly, rectal filling until MTV evoked negative responses compared to baseline throughout the cortex. No negative side effects were found. DISCUSSION: This study shows that a standardized paradigm for functional MRI combined with rectal filling is feasible and safe in healthy volunteers and is ready to be used in fecal incontinent patients to assess whether their brain activity differs from healthy controls.

Selected stage IV rectal cancer patients managed by the watch-and-wait approach after pelvic radiotherapy: a good alternative to total mesorectal excision surgery?

AIM: The aim of this study was to assess the clinical and oncological outcome of a selected group of stage IV rectal cancer patients managed by the watch-and-wait approach following a (near-)complete response of the primary rectal tumour after radiotherapy. METHOD: Patients registered in the Dutch watch-and-wait registry since 2004 were selected when diagnosed with synchronous stage IV rectal cancer. Data on patient characteristics, treatment details, follow-up and survival were collected. The 2-year local regrowth rate, organ-preservation rate, colostomy-free rate, metastatic progression-free rate and 2- and 5-year overall survival were analysed. RESULTS: After a median follow-up period of 35 months, local regrowth was observed in 17 patients (40.5%). Nine patients underwent subsequent total mesorectal excision, resulting in a permanent colostomy in four patients. The 2-year local regrowth rate was 39.9%, the 2-year organ-preservation rate was 77.1%, the 2-year colostomy-free rate was 88.1%, and the 2-year metastatic progression-free rate was 46.7%. The 2- and 5-year overall survival rates were 92.0% and 67.5%. CONCLUSION: The watch-and-wait approach can be considered as an alternative to total mesorectal excision in a selected group of stage IV rectal cancer patients with a (near-)complete response following pelvic radiotherapy. Despite a relatively high regrowth rate, total mesorectal excision and a permanent colostomy can be avoided in the majority of these patients.

Patient reported outcome measure-haemorrhoidal impact and satisfaction score (PROM-HISS): Development, reliability and construct validity.

AIM: Haemorrhoidal disease (HD) is a frequently occurring disorder with a significant negative impact on a patient's quality of life. Here, we describe the development and validation of the Dutch patient reported outcome measure-haemorrhoidal impact and satisfaction score (PROM-HISS). METHODS: The development of the PROM-HISS followed recommended guidelines. Face and content validity, structural properties, reliability and construct validity were evaluated in a HD population. Reliability was tested by assessing the test-retest reliability, defined by the intraclass correlation coefficient (ICC), and internal consistency measured with Cronbach's alpha. Construct validity was evaluated using confirmatory factor analysis (CFA) and hypotheses testing. RESULTS: The PROM-HISS consists of three domains: (1) HD symptoms (blood loss; pain; prolapse; soiling; itching), (2) impact of symptoms on daily activities, and (3) satisfaction with treatment. The PROM-HISS showed good face and content validity. The PROM-HISS was completed by 102 patients (65% male), with a mean age of 58 years (23-81 years). The ICCs of the different items in the domain HD symptoms ranged between 0.56 and 0.79 and were interpreted as good. The Cronbach's alpha value was 0.80 and considered satisfactory. The CFA provided further evidence for construct validity with a good model fit. A high score on the symptoms of HD correlated with a high impact of HD on daily activities (Pearson's r = 0.632, p < 0.01) and a low degree of satisfaction (Pearson's r = 0.378, p < 0.01). CONCLUSION: The PROM-HISS is a reliable and valid instrument to evaluate symptoms of HD, impact on daily activities and satisfaction with treatment.

Living with cryptoglandular anal fistula: a qualitative investigation of the patient's experience through semi-structured patient interviews.

PURPOSE: Cryptoglandular anal fistula continues to be a subject of extensive surgical research due to the lack of effective and enduring treatments, some of which incur risks to continence and quality of life. However, the patient experience of disease has seldom been reported. The aims of this study are to understand the impact of living with a fistula and the treatment outcomes that are valued by patients. METHODS: Patients with cryptoglandular anal fistula were recruited using purposive sampling from two tertiary referral centres in the UK and the Netherlands. Patients underwent semi-structured interviews that were audio-recorded and transcribed verbatim. Dutch transcripts were translated into English and underwent independent, thematic analysis using open coding by two study team members to identify common themes and sub-themes. RESULTS: Twenty interviews were conducted before saturation was reached (11 male, median age 49, Interquartile range 39-55 years). Four broad themes emerged, covering the physical symptoms of fistula, the patient journey towards understanding the condition, life impact, and treatment. Several inter-related sub-themes were found, reflecting the extensive impact and adjustment that the disease entails. CONCLUSION: The impact of cryptoglandular anal fistula extends beyond the physical symptoms of pain and discharge, requires significant readjustment, and often negatively impacts psycho-social wellbeing. These aspects of disease should receive greater attention in future assessment of treatment and quality of life.