Transitional Care for Patients with Congenital Colorectal Diseases: An EUPSA Network Office, ERNICA, and eUROGEN Joint Venture.

BACKGROUND: Transition of care (TOC; from childhood into adulthood) of patients with anorectal malformations (ARM) and Hirschsprung disease (HD) ensures continuation of care for these patients. The aim of this international study was to assess the current status of TOC and adult care (AC) programs for patients with ARM and HD. METHODS: A survey was developed by members of EUPSA, ERN eUROGEN, and ERNICA, including patient representatives (ePAGs), comprising of four domains: general information, general questions about transition to adulthood, and disease-specific questions regarding TOC and AC programs. Recruitment of centres was done by the ERNs and EUPSA, using mailing lists and social media accounts. Only descriptive statistics were reported. RESULTS: In total, 82 centres from 21 different countries entered the survey. Approximately half of them were ERN network members. Seventy-two centres (87.8%) had a self-reported area of expertise for both ARM and HD. Specific TOC programs were installed in 44% of the centres and AC programs in 31% of these centres. When comparing centres, wide variation was observed in the content of the programs. CONCLUSION: Despite the awareness of the importance of TOC and AC programs, these programs were installed in less than 50% of the participating centres. Various transition and AC programs were applied, with considerable heterogeneity in implementation, content and responsible caregivers involved. Sharing best practice examples and taking into account local and National Health Care Programs might lead to a better continuation of care in the future. LEVEL OF EVIDENCE: III.

The Transition of Care for Patients with Anorectal Malformations and Hirschsprung Disease: A European Survey.

This study aimed at evaluating how transition of care is currently being organized in the European Reference Networks (ERNs) health care providers (HCPs) in pediatric areas and in the Anorectal Malformation Network (ARM-Net) Consortium hospitals. An online questionnaire was sent to a total of 80 surgeons, members of or affiliated members of three networks: ARM-Net Consortium, ERN eUROGEN, and ERN ERNICA. Complete information were obtained for 45 HCPs, most of which deal with transition and still see a few adult patients (ca. 10%). Gynecological, gastroenterological, urological, colorectal, and continence issues were the major problems described by adult patients to their physicians, and in line with these prevalent complaints, they are referred to the appropriate adult specialists. Forty percent of patients complain about sexual and fertility problems, but the percentage of andrologists and sexologists involved in the caring of adult patients with ARM/Hirschsprung's disease is low, just above 10.9%. Most hospitals deal with transition, but three basic criteria (i.e., presence of: [1] an official written transitional program, [2] a transitional coordinator, and [3] written information on transition to be handled to patients) are jointly met only by six HCPs. According to the responders, the most important issue requiring improvement is the lack of interest and of specific preparation by adult specialists. The overall results of this exploratory survey confirm the need for the development of comprehensive programs for transition in these rare and complex diseases, and identify the hospitals that, in collaboration with the networks, could share best practices in organizing structured transitional pathways and well follow-ups.

Genome-wide identification of disease-causing copy number variations in 450 individuals with anorectal malformations.

Anorectal malformations (ARM) represent a spectrum of rare malformations originating from a perturbated development of the embryonic hindgut. Approximately 60% occur as a part of a defined genetic syndrome or within the spectrum of additional congenital anomalies. Rare copy number variations (CNVs) have been associated with both syndromic and non-syndromic forms. The present study represents the largest study to date to explore the contribution of CNVs to the expression of ARMs. SNP-array-based molecular karyotyping was applied in 450 individuals with ARM and 4392 healthy controls. CNVs were identified from raw intensity data using PennCNV. Overlapping CNVs between cases and controls were discarded. Remaining CNVs were filtered using a stringent filter algorithm of nine filter steps. Prioritized CNVs were confirmed using qPCR. Filtering prioritized and qPCR confirmed four microscopic chromosomal anomalies and nine submicroscopic CNVs comprising seven microdeletions (del2p13.2, del4p16.2, del7q31.33, del9p24.1, del16q12.1, del18q32, del22q11.21) and two microduplications (dup2p13.2, dup17q12) in 14 individuals (12 singletons and one affected sib-pair). Within these CNVs, based on their embryonic expression data and function, we suggest FOXK2, LPP, and SALL3 as putative candidate genes. Overall, our CNV analysis identified putative microscopic and submicroscopic chromosomal rearrangements in 3% of cases. Functional characterization and re-sequencing of suggested candidate genes is warranted.

Urinary and Fecal Continence in Adolescent and Adult Patients With Cloacal Exstrophy.

OBJECTIVE: To evaluate the prevalence of urinary (UI) and fecal incontinence (FI) and the incontinence-related quality of life (QoL) in adolescent and adult patients with cloacal exstrophy (CE) in Germany. PATIENTS AND METHODS: CE-patients of a tertiary care center and the German support group for anorectal malformations (SoMA e.V.) were included (October 2015 until September 2020). Data were assessed using a composed questionnaire consisting of 18 self-generated questions and two validated German questionnaires (King's health questionnaire, Questionnaire on Quality of Life in Fecal Incontinence (FLQAI)). RESULTS: Out of 23 included patients, 19 had continent and 3 incontinent urinary diversions (UD), 1 was unspecified; 2/23 were on dialysis. 73.7% (14/19) had undergone bladder augmentation, 4/19 had a pouch, 1/19 a neobladder. 94.7% (18/19) had a continent cutaneous channel and performed intermittent self-catheterization. UI was common (71.4%, 15/21). Neither the UD nor the involuntary loss of urine itself had a significant impact on QoL. Comparing the King's health questionnaire results, UI-related QoL of CE-patients was significantly lower than in a published reference group. 78.3% (18/23) had a bowel stoma. 34.8% (8/23) reported involuntary stool-soiling. Neither the way of bowel-emptying nor involuntary stool-soiling itself showed significant influence on FI-related QoL in the FLQAI. FLQAI items showed significant differences only for one of two published reference groups. CONCLUSION: Long-term incontinence rates in adolescent and adult CE-patients are high. Incontinence-related QoL was reduced compared to published reference groups but was minimally influenced by incontinence itself, the type of UD or the way of bowel-emptying, respectively.

Importance of education and the role of the patient and family in the care of anorectal malformations.

During this early part of the 21st century online technology has prompted many major advances in medical care. In this section we argue that this is particularly evident in the treatment and care of patients born with Anorectal Malformation (ARM) and Hirschsprung's Disease (HD). Our stories show that anyone born with these complex colorectal conditions in the 20th century was destined to a life of isolation and stigma. Here we explore the lack of understanding and recognition of the psychological effects on children and families which has characterised this period. We show that advances in clinical practice has been supported by developing social media platforms. There has been a rapid creation of online support groups for patients and families which has enabled survivors' greater access to patient and parent organizations across the globe and thereby stimulated a sense of belonging and solidarity. Online technology and social media platforms have also opened up the opportunity for pediatric medical professionals to provide a greater level of patient education. There is no doubt families have become much more aware of the complexities of ARM & HD and achieved greater comfort and understanding of their needs. We have generated "lightbulb moments" for pediatric providers with adult ARM & HD patients, enabling them to share their lived experiences in a therapeutic exchange. In the past survivors felt they were abandoned by the adult healthcare system. We are seeing evidence-based research of major psychosocial issues experienced by adult patients and, as a result, improved understanding of how to treat ARM & HD survivors across their whole of life journey. The winds of change continue to direct our cohorts to a mature approach based on improving levels of interactive communication and education. We argue that this maturity has mostly been facilitated by the use of online technology and the ensuing collaboration between providers and patient and parent organizations.

A Genetics-First Approach Revealed Monogenic Disorders in Patients With ARM and VACTERL Anomalies.

Background: The VATER/VACTERL association (VACTERL) is defined as the non-random occurrence of the following congenital anomalies: Vertebral, Anal, Cardiac, Tracheal-Esophageal, Renal, and Limb anomalies. As no unequivocal candidate gene has been identified yet, patients are diagnosed phenotypically. The aims of this study were to identify patients with monogenic disorders using a genetics-first approach, and to study whether variants in candidate genes are involved in the etiology of VACTERL or the individual features of VACTERL: Anorectal malformation (ARM) or esophageal atresia with or without trachea-esophageal fistula (EA/TEF). Methods: Using molecular inversion probes, a candidate gene panel of 56 genes was sequenced in three patient groups: VACTERL (n = 211), ARM (n = 204), and EA/TEF (n = 95). Loss-of-function (LoF) and additional likely pathogenic missense variants, were prioritized and validated using Sanger sequencing. Validated variants were tested for segregation and patients were clinically re-evaluated. Results: In 7 out of the 510 patients (1.4%), pathogenic or likely pathogenic variants were identified in SALL1, SALL4, and MID1, genes that are associated with Townes-Brocks, Duane-radial-ray, and Opitz-G/BBB syndrome. These syndromes always include ARM or EA/TEF, in combination with at least two other VACTERL features. We did not identify LoF variants in the remaining candidate genes. Conclusions: None of the other candidate genes were identified as novel unequivocal disease genes for VACTERL. However, a genetics-first approach allowed refinement of the clinical diagnosis in seven patients, in whom an alternative molecular-based diagnosis was found with important implications for the counseling of the families.

ERNICA guidelines for the management of rectosigmoid Hirschsprung's disease.

BACKGROUND: Hirschsprung's disease (HSCR) is a serious congenital bowel disorder with a prevalence of 1/5000. Currently, there is a lack of systematically developed guidelines to assist clinical decision-making regarding diagnostics and management. AIMS: This guideline aims to cover the diagnostics and management of rectosigmoid HSCR up to adulthood. It aims to describe the preferred approach of ERNICA, the European Reference Network for rare inherited and congenital digestive disorders. METHODS: Recommendations within key topics covering the care pathway for rectosigmoid HSCR were developed by an international workgroup of experts from 8 European countries within ERNICA European Reference Network from the disciplines of surgery, medicine, histopathology, microbiology, genetics, and patient organization representatives. Recommendation statements were based on a comprehensive review of the available literature and expert consensus. AGREE II and GRADE approaches were used during development. Evidence levels and levels of agreement are noted. RESULTS: Thirty-three statements within 9 key areas were generated. Most recommendations were based on expert opinion. CONCLUSION: In rare or low-prevalence diseases such as HSCR, there remains limited availability of high-quality clinical evidence. Consensus-based guidelines for care are presented.

What do pediatric surgeons think about sexual issues in dealing with patients with anorectal malformations? The ARM-Net consortium members' opinion.

PURPOSE: Since pediatric surgeons aim to follow their patients with anorectal malformations (ARM) into adulthood the aim of this study was to investigate how pediatric surgeons deal with sexual issues related to ARM. METHODS: In 2018, a questionnaire was developed by the working group "Follow-up and sexuality" of the ARM-Net consortium and sent to all consortium-linked pediatric surgeons from 31 European pediatric surgical centers. Obtained data were statistically analyzed. RESULTS: Twenty-eight of 37 pediatric surgeons (18 males/10 females) answered the questionnaire. The majority of pediatric surgeons (82%) think they should talk about sexual issues with their patient. More than 50% of pediatric surgeons do not feel at all or only moderately confident discussing the topic of sexuality. Most pediatric surgeons require more support (96%) and wish to be trained in sexuality and sexual issues (78%) to feel confident towards their ARM-patients/parents. For optimal care, sexual issues with ARM-patients should be managed by a multidisciplinary team. CONCLUSIONS: Pediatric surgeons feel that sexuality is an important issue for their ARM-patients, which they are primarily responsible of but should be managed in concert with a multidisciplinary team. A training in sexuality is wished to feel more confident about this specific issue.

Needs Assessment in Care of Adults With Anorectal Malformations and Exstrophy-Epispadias Complex in Germany.

Introduction: Medical needs of adults with anorectal malformations (ARM) and the exstrophy-epispadias complex (EEC) are not fully understood. Therefore, the aim of the study was to evaluate how affected individuals get along with the current national medical care and what their medical or social long-term requirements are. Patients and Methods: Between 11/2014-07/2016 all adult members (≥18 years, ARM n = 113, EEC n = 126) of the German self-help organizations SoMA e.V. and Blasenekstrophie/Epispadie e.V. were contacted via email or post and asked to fill out an anonymous online questionnaire regarding medical requirements, treatment satisfaction, daily life impairment and expectations regarding physicians soft skills. The results were compared between both groups and male and female participants. Results: 56 participants with ARM (median age 26 years, IQR 19-38) and 52 participants with EEC (median age 31 years, IQR 22-37) filled in the questionnaire completely. Forty-five percent of the ARM and 67% of the EEC participants contacted an urologist. A general surgeon was visited by 23% of the ARM individuals, a peadiatric surgeon by 20%. Although 60% of the females with ARM and 82% of the females with EEC assessed gynecological counseling as helpful or neutral, a small subgroup of ARM females (n = 6, 16%; 70% non-isolated ARM or ARM with Hirschsprung disease and additional associated anomalies) were not satisfied. The majority of both groups reported no or only minor daily life impairment (p = 0.38). Professional knowledge, paying attention to patients' concerns, having empathy and taking enough time was important for over 90% of all participants. Thirty-eight percent of the ARM and 27% of the EEC individuals needed psychological support. Most medical consultations were judged to be helpful. Conclusion: Although adults with ARM and EEC being a self-help organization member and thus well informed and generally cope well, participants expressed their wish for expert counseling regarding family planning, reconstructive procedures, continence management, urological care and social welfare issues. Furthermore, specific expert consultations for gynecological issues in a subgroup of ARM females, mainly non-isolated, might be required. Actual needs of adults with rare conditions must be better clarified to improve medical care beyond childhood and adolescence.

Transition of care in patients with anorectal malformations: Consensus by the ARM-net consortium.

OBJECTIVES: To develop the first consensus to standardize the management of patients with Anorectal Malformations (ARMs) transitioning from childhood to adulthood. METHODS: A dedicated task force of experts performed an extensive literature review and multiple meetings to define the most important aspects of transition of care. The findings were discussed with all ARM-net consortium members and a set of practical recommendations agreed upon at the annual meeting in 2016. RESULT: We defined seven domains that are essential to provide an effective and practical transition process. Within each domain we have developed a set of key recommendations that are important to be considered for ARM patients entering the age of transition. CONCLUSIONS: It is crucial that transition begins at an early age with regular and well-structured follow-up. Cooperation with a selected multidisciplinary team of pediatric and adult practitioners is required to prepare patients and families for effective transition to adult care and to reduce long term morbidity. TYPE OF STUDY: Review/Consensus paper. LEVEL OF EVIDENCE: III.

The Challenges of the European Anorectal Malformations-Net Registry.

Anorectal malformations (ARM) have a low prevalence, patients need specialized surgical care, and in many cases, patients born with ARM even need life-long aftercare. Due to its low prevalence most patients are still treated in low-volume pediatric surgical centers without any adequate monitoring of the outcome. Data on prevalence, comparison of different surgical techniques, and prospective outcome measurements are still scarce and difficult to interpret. In 2010, a consortium was founded (ARM-Net consortium) including several European pediatric surgical centers to collaborate more in research and share knowledge on ARM. One of the structures started by the consortium was an ARM-Net registry for the inclusion of all future patients treated in these centers. With this review, we report the structure of the ARM-Net registry, some of the results, and discuss the challenges we faced and still face after its introduction in 2010.

First results of a European multi-center registry of patients with anorectal malformations.

BACKGROUND: The European consortium on anorectal malformations (ARM-NET) was established to improve the health care of patients and to identify genetic and environmental risk factors. The aim of the present study was to present the first results on clinical data of a large European cohort of ARM patients based on our registry. METHODS: In 2010, the registry was established including patient characteristics and data on diagnosis, surgical therapy, and outcome regarding complications. Patients born between 2007 and 2012 were retrospectively added. A descriptive analysis of this cohort was performed. RESULTS: Two hundred and three ARM patients were included. Syndromes or chromosomal abnormalities were present in 9%. Perineal fistulas were seen most in boys (42%) and girls (29%). Rare forms of ARM were found in 4% of the male and in 14% of the female patients. Forty-five percent of the patients had additional urogenital abnormalities. However, 32% of the patients were never screened for bladder abnormalities. Eight percent were never screened for renal malformations. In the majority of patients (79%), a PSARP was performed for the definitive reconstruction. CONCLUSION: This collaborative effort provides a representative basis to estimate incidence of ARM types, to discuss differences and similarities in treatment, and health consequences throughout Europe.

Assisted reproductive techniques and the risk of anorectal malformations: a German case-control study.

BACKGROUND: The use of assisted reproductive techniques (ART) for treatment of infertility is increasing rapidly worldwide. However, various health effects have been reported including a higher risk of congenital malformations. Therefore, we assessed the risk of anorectal malformations (ARM) after in-vitro fertilization (IVF) and intracytoplasmic sperm injection (ICSI). METHODS: Data of the German Network for Congenital Uro-REctal malformations (CURE-Net) were compared to nationwide data of the German IVF register and the Federal Statistical Office (DESTATIS). Odds ratios (95% confidence intervals) were determined to quantify associations using multivariable logistic regression accounting for potential confounding or interaction by plurality of births. RESULTS: In total, 295 ARM patients born between 1997 and 2011 in Germany, who were recruited through participating pediatric surgeries from all over Germany and the German self-help organisation SoMA, were included. Controls were all German live-births (n = 10,069,986) born between 1997 and 2010. Overall, 30 cases (10%) and 129,982 controls (1%) were born after IVF or ICSI, which translates to an odds ratio (95% confidence interval) of 8.7 (5.9-12.6) between ART and ARM in bivariate analyses. Separate analyses showed a significantly increased risk for ARM after IVF (OR, 10.9; 95% CI, 6.2-19.0; P < 0.0001) as well as after ICSI (OR, 7.5; 95% CI, 4.6-12.2; P < 0.0001). Furthermore, separate analyses of patients with isolated ARM, ARM with associated anomalies and those with a VATER/VACTERL association showed strong associations with ART (ORs 4.9, 11.9 and 7.9, respectively). After stratification for plurality of birth, the corresponding odds ratios (95% confidence intervals) were 7.7 (4.6-12.7) for singletons and 4.9 (2.4-10.1) for multiple births. CONCLUSIONS: There is a strongly increased risk for ARM among children born after ART. Elevations of risk were seen after both IVF and ICSI. Further, separate analyses of patients with isolated ARM, ARM with associated anomalies and those with a VATER/VACTERL association showed increased risks in each group. An increased risk of ARM was also seen among both singletons and multiple births.

Unexpected results of a nationwide, treatment-independent assessment of fecal incontinence in patients with anorectal anomalies.

PURPOSE: To determine the anorectal function in patients with anorectal malformations (ARM) in order to facilitate patient counseling and follow-up. METHODS: Data were collected by the German network for urorectal malformations (CURE-Net) according to the International Krickenbeck consensus. Questionnaires on bowel function and a defecation protocol were completed by the families/patients. The clinical findings were assessed from the patients' clinical records. RESULTS: Two hundred and ninety-seven patients with ARM were assessed, 175 patients gave complete data on continence, 52 of them were excluded due to mental retardation, age, and earlier type of pullthrough. Complete continence was found in 27 %, perineal fistula in 40 %, rectourethral/vesical in 10 %, vestibular in 24 %, cloaca in 0 %. Krickenbeck grade 1 soiling: 42 %, grade 2 and 3: 31 %. Forty-nine percent of the incontinent patients practiced bowel management, reaching continence in 19 %. The statement of constipation (67 %) was validated with the last clinical findings, showing coprostasis in 46 %, "Not suffering constipation" was confirmed in 61 % and falsified in 29 %. CONCLUSION: ARM patients in Germany, as assessed by independent researchers, show a high rate of fecal incontinence and insufficiently treated constipation. Parents should be counseled accordingly and motivated to engage in consequent follow-up. Intensified efforts in the conservative treatment of constipation and fecal incontinence are crucial to improvement.

German network for congenital uro-rectal malformations: first evaluation and interpretation of postoperative urological complications in anorectal malformations.

OBJECTIVE: The aim of the German Network for Congenital Uro-REctal Malformations is to collect data of affected patients with anorectal malformation (ARM) or extrophy-epispadias complex, and to investigate molecular causes, clinical implications, and psychosocial outcome. The current issue was to assess the postoperative sequelae related to lower urinary tract dysfunction in patients with ARM. MATERIALS AND METHODS: Two hundred and sixty-seven patients with ARM (112 females, 155 males, median age 6 years, range 0-56 years) were investigated via standardized case report forms comprising interview, analysis of medical data, and personal questionnaires. RESULTS: Thirty-two patients (12%, 23 males, 9 females) suffered from neurogenic bladder dysfunction, mainly associated with recto-urethral fistula (11 cases, 34%), and recto-vesical fistula (6 cases, 19%). Sixty-eight patients (26%, 35 males, 57 females) have experienced lifetime urinary tract infection, primarily associated with recto-urethral fistula (21 cases, 31%), and vestibular fistula (13 cases, 19%). According to type of operation, the highest number of postoperative urologic problems was reported after abdominosacroperineal pull-through. CONCLUSION: Besides reconstructing the ARM, another main goal is the preservation of lower urinary tract function. In our data, there seems to be a close correlation between operative strategies and postoperative complications.

[How could self help support patients and families with anorectal malformations?--Psychosocial help offers of SoMA eV]. / Wie kann Selbsthilfe Patienten mit anorektalen Fehlbildungen und ihre Familien unterstützen? Psychosoziale Hilfsangebote von SoMA e.V.

To be born with an anorectal malformation means to suffer from a rare disease. The afflicted viscera and the consequences e. g. incontinence border on a taboo. In most instances it is necessary to have an interdisciplinary and long-term follow up of the patients. Involved children and their families benefit in a special way from the offers of a self-help organization. The feeling not to be alone helps to cope with the strain situation, as do the presented projects and offers which come up with the special needs of the patients. The everyday experience and capacity of the patients can be used to solve problems. On the one hand, self-help represents a pool of knowledge on the other hand it shows to the attending physician or therapist the long-term results achieved. Here a network of the different specialties is crucial. Especially in the psychosocial field where self-help organizations have reached their limits--there is a need for more psychotherapeutical support.