European Reference Network eUROGEN Guidelines on the Management of Anorectal Malformations, Part II: Treatment.

INTRODUCTION: Anorectal malformations (ARMs) are rare birth defects affecting the anorectum and oftentimes the genitourinary region. The management of ARM patients is complex and requires highly specialized surgical and medical care. The European Reference Network eUROGEN for rare and complex urogenital conditions aimed to develop comprehensive guidelines for the management of ARM applicable on a European level. METHODS: The Dutch Quality Standard for ARM served as the basis for the development of guidelines. Literature was searched in Medline, Embase, and Cochrane. The ADAPTE method was utilized to incorporate the newest available evidence. A panel of 15 experts from seven European countries assessed currency, acceptability, and applicability of recommendations. Recommendations from the Dutch Quality Standard were adapted, adopted, or rejected and recommendations were formed considering the current evidence, expert opinion, and the European context. RESULTS: Surgical and medical treatment of ARM, postoperative instructions, toilet training, and management of fecal and urinary incontinence were addressed. Seven new studies were identified. The panel adapted 23 recommendations, adopted 3, and developed 8 de novo. The overall level of newly found evidence was considered low. CONCLUSION: Treatment of ARM patients requires a multidisciplinary team and expertise about anatomical and surgical aspects of the disease, as well as long-term follow-up. This guideline offers recommendations for surgical and medical treatment of ARM and associated complications, according to the best available evidence and applicable on a European level.

ERN eUROGEN Guidelines on the Management of Anorectal Malformations Part III: Lifelong Follow-up and Transition of Care.

INTRODUCTION: Anorectal malformations (ARMs) are complex congenital anomalies of the anorectal region, oftentimes also affecting the genitourinary system. Although successful surgical correction can often be achieved in the neonatal period, many children will experience functional problems in the long term. The European Reference Network for rare and complex urogenital conditions (eUROGEN) assembled a panel of experts to address these challenges and develop comprehensive guidelines for the management of ARM. METHODS: The Dutch Quality Standard for ARM served as the foundation for the development of guidelines applicable on a European level. Literature was searched in Medline, Embase, and Cochrane. The ADAPTE method was utilized to incorporate the newest available evidence. A panel of 15 experts from 7 European countries assessed currency, acceptability, and applicability of recommendations. Recommendations from the Dutch Quality Standard were adapted, adopted, or rejected and recommendations were formed considering the current evidence and/or expert consensus. RESULTS: Lifelong follow-up, integration, and transition of care were assessed. A total of eight new studies were identified. The panel adapted 18 recommendations, adopted 6, and developed 6 de novo. Overall, the level of evidence was considered low. CONCLUSION: Successful lifelong follow-up and transition of care require a dedicated team of pediatric and adult specialist and an individually tailored patient-centered approach. This guideline summarizes the best available evidence on follow-up of ARM patients and provides guidance for the development of structured transition programs.

Transcatheter arterial embolization for small-bowel bleeding: technical and clinical outcomes and risk factors for early recurrent bleeding.

Background: This study evaluated the technical and clinical outcomes of transcatheter arterial embolization (TAE) in patients with acute small-bowel bleeding (SBB) and aimed to identify potential risk factors for early recurrent bleeding after TAE. Methods: Thirty-one patients with SBB managed with TAE between January 2006 and December 2021 were included. Technical and clinical success was defined as angiographic occlusion of the bleeding artery and disappearance of clinical or laboratory signs of persistent bleeding without major complications. Complications were classified according to the Society of Interventional Radiology's guidelines. Kaplan-Meier estimates assessed overall survival, and logistic regression models determined risk factors for clinical success and early rebleeding. Results: Technical and clinical success were achieved in 30/31 (97%) and 19 (61%), respectively. Early recurrent bleeding was present in 9 (29%) patients, and was treated by repeat embolization in 4 patients, conversion to surgery in 4, and comfort therapy in 1 patient. TAE-related small bowel ischemia requiring surgery was found in 2 (6.5%) patients. Thirty-day and in-hospital mortality were 19% (6/31) and 23% (7/31), respectively; overall 5-year estimated survival was 60%. Thrombocytopenia and elevated prothrombin time (PT)/activated partial thromboplastin time (aPTT) levels prior to TAE were identified as risk factors for clinical failure (P=0.0026 and P=0.027, respectively), and for residual or early recurrent bleeding (P<0.001 and P=0.01, respectively). Conclusions: TAE is safe and effective for managing severe SBB; however, early recurrent bleeding was found in nearly one third of patients. Thrombocytopenia and elevated PT/aPTT levels were risk factors for early recurrent bleeding.

Incidence of contralateral metachronous inguinal hernia on long term follow-up after unilateral inguinal hernia repair: a systematic review and meta-analysis.

BACKGROUND: The repair of inguinal hernias is a common surgical procedure. Some patients will need a second operation after developing a metachronous contralateral inguinal hernia (MCIH). The suggestion has been made to strengthen the contralateral side at the same time as primary unilateral surgery. In this systematic review we aim to determine how many adult patients with a unilateral inguinal hernia will develop a MCIH. METHODS: This review was reported in line with PRISMA guidelines. We performed a literature review in PubMed Publisher, Embase, Google Scholar and Cochrane Library until May 2021, including articles reporting MCIH after unilateral inguinal hernia repair in adults. As outcome measure, the number of patients diagnosed with a MCIH was registered. RESULTS: A total of 19 articles with a total of 277,288 patients were included. The combined estimate for MCIH after meta-analysis equaled 8.3% (95% CI 7.1%-9.5%), with a high index of heterogeneity (I2 = 97.9%). A random-effects meta-regression was performed to obtain the percentage of MCIH as a function of median follow-up time. The percentage of MCIH at 3, 5 and 10 years was estimated at 5.2%, 8.0% and 17.1%, respectively. CONCLUSION: We suggest that there is insufficient clinical evidence to support prophylactic contralateral repair in all patients. We propose a patient-specific approach in the decision to perform prophylactic repair, taking into account potential risk factors for hernia development, type of surgical approach, and general risk factors for chronic postoperative inguinal pain. More long-term prospective data are needed to guide the decision for prophylactic contralateral mesh placement.

Ernica Clinical Consensus Statements on Total Colonic and Intestinal Aganglionosis.

BACKGROUND: Hirschsprung disease is a congenital intestinal motility disorder characterized by an absence of enteric ganglion cells. Total colonic aganglionosis and near total or total intestinal aganglionosis, defined as absence of ganglion cells in the entire colon and with variable length of small bowel involved, are life-threatening conditions which affect less than 10 % of all patients with Hirschsprung disease. The aim of this project was to develop clinical consensus statements within ERNICA, the European Reference Network for rare congenital digestive diseases, on four major topics: Surgical treatment of total colonic aganglionosis, surgical treatment of total intestinal aganglionosis, management of poor bowel function in total colonic and/or intestinal aganglionosis and long-term management in total colonic and or intestinal aganglionosis. METHODS: A multidisciplinary panel of representatives from ERNICA centers was invited to participate. Literature was searched, using specified search terms, in Medline (ALL), Embase and Google Scholar. Abstracts were screened and full text publications were selected. The panel was divided in four groups that extracted data from the full text publications and suggested draft statements for each of the major topics. A modified Delphi process was used to refine and agree on the statements. RESULTS: The consensus statement was conducted by a multidisciplinary panel of 24 participants from 10 European countries, 45 statements reached consensus after 3 Delphi-rounds. The availability of high-quality clinical evidence was limited, and most statements were based on expert opinion. Another 25 statements did not reach consensus. CONCLUSIONS: Total colonic and total intestinal aganglionosis are rare variants of Hirschsprung disease, with very limited availability of high-quality clinical evidence. This consensus statement provides statements on the surgical treatment, management of poor bowel function and long-term management for these rare patients. The expert panel agreed that patients benefit from multidisciplinary and personalized care, preferably in an expert center. TYPE OF STUDY: Clinical consensus statement. LEVEL OF EVIDENCE: 3a.

Expression of intestinal drug transporter proteins and metabolic enzymes in neonatal and pediatric patients.

The development of pediatric oral drugs is hampered by a lack of predictive simulation tools. These tools, in turn, require data on the physiological variables that influence oral drug absorption, including the expression of drug transporter proteins (DTPs) and drug-metabolizing enzymes (DMEs) in the intestinal tract. The expression of hepatic DTPs and DMEs shows age-related changes, but there are few data on protein levels in the intestine of children. In this study, tissue was collected from different regions of the small and large intestine from neonates (i.e., surgically removed tissue) and from pediatric patients (i.e., gastroscopic duodenal biopsies). The protein expression of clinically relevant DTPs and DMEs was determined using a targeted mass spectrometry approach. The regional distribution of DTPs and DMEs was similar to adults. Most DTPs, with the exception of MRP3, MCT1, and OCT3, and all DMEs showed the highest protein expression in the proximal small intestine. Several proteins (i.e., P-gp, ASBT, CYP3A4, CYP3A5, CYP2C9, CYP2C19, and UGT1A1) showed an increase with age. Such increase appeared to be even more pronounced for DMEs. This exploratory study highlights the developmental changes in DTPs and DMEs in the intestinal tract of the pediatric population. Additional evaluation of protein function in this population would elucidate the implications of the presented changes in protein expression on absorption of orally administered drugs in neonates and pediatric patients.

European reference network for rare inherited congenital anomalies (ERNICA) evidence based guideline on the management of gastroschisis.

BACKGROUND: The European Reference Network for rare Inherited Congenital Anomalies, ERNICA, guidelines for gastroschisis cover perinatal period to help teams to improve care. METHOD: A systematic literature search including 136 publications was conducted. Research findings were assessed following the GRADE methodology. The evidence to decision framework was used to determine the strength and direction of recommendations. RESULTS: The mode or timing of delivery do not impact neonatal mortality, risk of NEC or time on parenteral nutrition (PN). Intra or extra abdominal bowel dilatation predict complex gastroschisis and longer length of hospital stay but not increased perinatal mortality. Outcomes after Bianchi procedure and primary fascia closure under anesthesia are similar. Sutureless closure decreases the rate of surgical site infections and duration of ventilation compared to surgical closure. Silo-staged closure with or without intubation results in similar outcomes. Outcomes of complex gastroschisis (CG) undergoing early or delayed surgical repair are similar. Early enteral feeds starting within 14 days is associated with lower risk of surgical site infection. RECOMMENDATIONS: The panel suggests vaginal birth between 37 and 39 w in cases of uncomplicated gastroschisis. Bianchi's approach is an option in simple gastroschisis. Sutureless closure is suggested when general anesthesia can be avoided, sutured closure. If anesthesia is required. Silo treatment without ventilation and general anesthesia can be considered. In CG with atresia primary intestinal repair can be attempted if the condition of patient and intestine allows. Enteral feeds for simple gastroschisis should start within 14 days.

Incidence and risk factors of metachronous contralateral inguinal hernia development up to 25 years after unilateral inguinal hernia repair: a single-centre retrospective cohort study.

BACKGROUND: Patients undergoing unilateral inguinal hernia repair (IHR) are at risk of metachronous contralateral inguinal hernia (MCIH) development. We evaluated incidence and risk factors of MCIH development up to 25 years after unilateral IHR to determine possible indications for concomitant prophylactic surgery of the contralateral groin at the time of primary surgery. METHODS: Patients between 18 and 70 years of age undergoing elective unilateral IHR in the University Hospital of Leuven from 1995 to 1999 were studied retrospectively using the electronic health records and prospectively via phone calls. Study aims were MCIH incidence and risk factor determination. Kaplan-Meier curves were constructed and univariable and multivariable Cox regressions were performed. RESULTS: 758 patients were included (91% male, median age 53 years). Median follow-up time was 21.75 years. The incidence of operated MCIH after 5 years was 5.6%, after 15 years 16.1%, and after 25 years 24.7%. The incidence of both operated and non-operated MCIH after 5 years was 5.9%, after 15 years 16.7%, and after 25 years 29.0%. MCIH risk increased with older age and decreased in primary right-sided IHR and higher BMI at primary surgery. CONCLUSION: The overall incidence of MCIH after 25-year follow-up is 29.0%. Potential risk factors for the development of a MCIH are primary left-sided inguinal hernia repair, lower BMI, and older age. When considering prophylactic repair, we suggest a patient-specific approach taking into account these risk factors, the surgical approach and the risk factors for chronic postoperative inguinal pain.

Gallbladder torsion: a rare cause of acute abdomen in a 12-month old child.

Background: Gallbladder torsion is a rare cause of an acute abdomen, predominantly occurring in elderly women and less frequently diagnosed in the pediatric population. The diagnosis is difficult and rarely made preoperatively. However, suspicion needs to be raised in children with acute onset of abdominal pain. Ultrasound can demonstrate different signs putting forward the diagnosis but findings are often non-specific, therefore clinical suspicion should prompt a laparoscopic exploration.Case presentation: We report a case of a 12-month old girl consulting with progressive abdominal discomfort and vomiting. Ultrasound revealed an enlarged gallbladder with thickening of the wall but without demonstrable color Doppler flow and a more horizontal orientation outside its normal anatomic fossa. Gallbladder torsion was suspected. Emergency laparoscopic exploration confirmed the diagnosis and a laparoscopic cholecystectomy was performed. The postoperative course was uneventful.Conclusions: Gallbladder torsion, although rare, should be included in the differential diagnosis of an acute abdomen in children. Early recognition is necessary for a favorable outcome. The diagnosis might be supported by ultrasound but remains difficult, which is why laparoscopic exploration should be considered when the diagnosis remains unclear.

Update of the international HerniaSurge guidelines for groin hernia management.

BACKGROUND: Groin hernia repair is one of the most common operations performed globally, with more than 20 million procedures per year. The last guidelines on groin hernia management were published in 2018 by the HerniaSurge Group. The aim of this project was to assess new evidence and update the guidelines. The guideline is intended for general and abdominal wall surgeons treating adult patients with groin hernias. METHOD: A working group of 30 international groin hernia experts and all involved stakeholders was formed and examined all new literature on groin hernia management, available until April 2022. Articles were screened for eligibility and assessed according to GRADE methodologies. New evidence was included, and chapters were rewritten. Statements and recommendations were updated or newly formulated as necessary. RESULTS: Ten chapters of the original HerniaSurge inguinal hernia guidelines were updated. In total, 39 new statements and 32 recommendations were formulated (16 strong recommendations). A modified Delphi method was used to reach consensus on all statements and recommendations among the groin hernia experts and at the European Hernia Society meeting in Manchester on October 21, 2022. CONCLUSION: The HerniaSurge Collaboration has updated the international guidelines for groin hernia management. The updated guidelines provide an overview of the best available evidence on groin hernia management and include evidence-based statements and recommendations for daily practice. Future guideline development will change according to emerging guideline methodology.

Rectal Biopsy for Hirschsprung's Disease: A Multicentre Study Involving Biopsy Technique, Pathology and Complications.

BACKGROUND: The heterogeneity of rectal biopsy techniques has encouraged us to search for a surgical and pathological standardisation of this diagnostic technique to exclude Hirschsprung's disease. The different amounts of information on the anatomopathology report prompted us to compile a template for the anatomopathology report for diagnostic rectal biopsies for surgical colleagues and pathologists working on Hirschsprung's disease. METHODS: We gathered the anonymous biopsy information and its pathology information from five hospitals for all patients in which rectal biopsies were taken to diagnose Hirschsprung's disease over two years (2020-2021). RESULTS: Of the 82 biopsies, 20 suction (24.4%), 31 punch (37.8%) and 31 open biopsies (37.8%) were taken. Of all biopsies, 69 were conclusive (84.2%), 13 were not (15.8%). In the suction biopsy group, 60% were conclusive and 40% were not; for punch biopsy, the values were 87% and 13%, respectively and for open biopsy, 97% and 3%. Inconclusive results were due to insufficient submucosa in 6/8 suction biopsies, 4/4 punch biopsies and 0/1 open biopsies. An insufficient amount of submucosa was the reason for an inconclusive result in 6/20 cases (30%) after suction biopsy, 4/31 (12.9%) cases after punch biopsy and 0 cases (0%) after open biopsy. We had one case with major postoperative bleeding post suction biopsy; there were no further adverse effects after biopsy. CONCLUSIONS: Diagnostic rectal biopsies in children are safe. Non-surgical biopsies are more likely to give inconclusive results due to smaller amounts of submucosa present in the specimen. Open biopsies are especially useful when previous non-surgical biopsies are inconclusive. An experienced pathologist is a key factor for the result. The anatomopathology report should specify the different layers present in the specimen, the presence of ganglion cells and hypertrophic nerve fibres, their description and a conclusion.

Effect of Degradation in Small Intestinal Fluids on Mechanical Properties of Polycaprolactone and Poly-l-lactide-co-caprolactone.

Polycaprolactone and poly-l-lactide-co-caprolactone are promising degradable biomaterials for many medical applications. Their mechanical properties, especially a low elastic modulus, make them particularly interesting for implantable devices and scaffolds that target soft tissues like the small intestine. However, the specific environment and mechanical loading in the intestinal lumen pose harsh boundary conditions on the design of these devices, and little is known about the degradation of those mechanical properties in small intestinal fluids. Here, we perform tensile tests on injection molded samples of both polymers during in vitro degradation of up to 70 days in human intestinal fluids. We report on yield stress, Young's modulus, elongation at break and viscoelastic parameters describing both materials at regular time steps during the degradation. These characteristics are bench-marked against degradation studies of the same materials in other media. As a result, we offer time dependent mechanical properties that can be readily used for the development of medical devices that operate in the small intestine.

Patient Satisfaction After Inguinal Hernia Surgery: Literature Review of an Overlooked Patient-Reported Outcome Measure.

INTRODUCTION: Patient satisfaction after inguinal hernia surgery is currently underappreciated and not as well studied as other patient-reported outcome measures (PROMs) on this topic. This study aims to review the literature and summarize available data. MATERIALS AND METHODS: A literature review was conducted using Medline with focus on patient-reported satisfaction after elective, inguinal hernia surgery in adults. All inguinal hernia repair techniques were considered. Small sample sizes and short follow-up periods were excluded. The methodology and results of the remaining articles were reviewed. Due to heterogeneity of reporting between articles, only a descriptive analysis was performed. RESULTS: The available data from patient-reported outcome measures regarding satisfaction yields considerable heterogeneity and lacks validation. We found that 53% of all included studies used an asymmetrical response questionnaire. Although there is an overwhelming positive patient satisfaction, wide ranges of satisfaction were seen (78-100% more than averagely satisfied, compared to 0-15% less than averagely satisfied). The number of patients not willing to undergo inguinal hernia repair again ranges from 1-16%. CONCLUSION: Our study demonstrates that patient-reported satisfaction after inguinal hernia surgery is not uniformly surveyed and remains unvalidated. Further research on patient-reported satisfaction would benefit from the reported raw data of a standardised, validated, and symmetrical five-point Likert or 11-point NRS scale on regular intervals pre- and postoperatively.

Prevention of Incisional Hernias by Prophylactic Mesh-augmented Reinforcement of Midline Laparotomies for Abdominal Aortic Aneurysm Treatment: Five-year Follow-up of a Randomized Controlled Trial.

INTRODUCTION: The incidence of incisional hernias (IHs) after open repair of an abdominal aortic aneurysm (AAA) is high. Several randomized controlled trials have reported favorable results with the use of prophylactic mesh to prevent IHs, without increasing complications. In this analysis, we report on the results of the 60-month follow-up of the PRIMAAT trial. METHODS: In a prospective, multicenter, open-label, randomized design, patients were randomized between prophylactic retrorectus mesh reinforcement (mesh group), and primary closure of their midline laparotomy after open AAA repair (no-mesh group). This article reports on the results of clinical follow-up after 60 months. If performed, ultrasonography or computed tomography were used for the diagnosis of IHs. RESULTS: Of the 120 randomized patients, 114 were included in the intention-to-treat analysis. Thirty-three patients in the no-mesh group (33/58-56.9%) and 34 patients in the mesh group (34/56-60.7%) were evaluated after 5 years. In each treatment arm, 10 patients died between the 24-month and 60-month follow-up. The cumulative incidence of IHs in the no-mesh group was 32.9% after 24 months and 49.2% after 60 months. No IHs were diagnosed in the mesh group. In the no-mesh group, 21.7% (5/23) underwent reoperation within 5 years due to an IH. CONCLUSIONS: Prophylactic retrorectus mesh reinforcement after midline laparotomy for the treatment of AAAs safely and effectively decreases the rate of IHs. The cumulative incidence of IHs after open AAA repair, when no mesh is used, continues to increase during the first 5 years after surgery, which leads to a substantial rate of hernia repairs.

Bowel function and associated risk factors at preschool and early childhood age in children with anorectal malformation type rectovestibular fistula: An ARM-Net consortium study.

BACKGROUND: Outcome of patients operated for anorectal malformation (ARM) type rectovestibular fistula (RVF) is generally considered to be good. However, large multi-center studies are scarce, mostly describing pooled outcome of different ARM-types, in adult patients. Therefore, counseling parents concerning the bowel function at early age is challenging. Aim of this study was to evaluate bowel function of RVF-patients at preschool/early childhood age and determine risk factors for poor functional outcome. METHODS: A multi-center cohort study was performed. Patient characteristics, associated anomalies, sacral ratio, surgical procedures, post-reconstructive complications, one-year constipation, and Bowel Function Score (BFS) at 4-7 years of follow-up were registered. Groups with below normal (BFS < 17; subgroups 'poor' ≤ 11, and 'fair' 11 < BFS < 17) and good outcome (BFS ≥ 17) were formed. Univariable analyses were performed to detect risk factors for outcome. RESULTS: The study included 111 RVF-patients. Median BFS was 16 (range 6-20). The 'below normal' group consisted of 61 patients (55.0%). Overall, we reported soiling, fecal accidents, and constipation in 64.9%, 35.1% and 70.3%, respectively. Bowel management was performed in 23.4% of patients. Risk factors for poor outcome were tethered cord and low sacral ratio, while sacral anomalies, low sacral ratio, prior enterostomy, post-reconstructive complications, and one-year constipation were for being on bowel management. CONCLUSIONS: Although median BFS at 4-7 year follow-up is nearly normal, the majority of patients suffers from some degree of soiling and constipation, and almost 25% needs bowel management. Several factors were associated with poor bowel function outcome and bowel management. LEVEL OF EVIDENCE: Level III.

Protocol to develop a core outcome set in incisional hernia surgery: the HarMoNY Project.

INTRODUCTION: Incisional hernia has an incidence of up to 20% following laparotomy and is associated with significant morbidity and impairment of quality of life. A variety of surgical strategies including techniques and mesh types are available to manage patients with incisional hernia. Previous works have reported significant heterogeneity in outcome reporting for abdominal wall herniae, including ventral and inguinal hernia. This is coupled with under-reporting of important clinical and patient-reported outcomes. The lack of standardisation in outcome reporting contributes to reporting bias, hinders evidence synthesis and adequate data comparison between studies. This project aims to develop a core outcome set (COS) of clinically important, patient-oriented outcomes to be used to guide reporting of future research in incisional hernia. METHODS: This project has been designed as an international, multicentre, mixed-methods project. Phase I will be a systematic review of current literature to examine the current clinical and patient-reported outcomes for incisional hernia and abdominal wall reconstruction. Phase II will identify the outcomes of importance to all key stakeholders through in depth qualitative interviews. Phase III will achieve consensus on outcomes of most importance and for inclusion into a COS through a Delphi process. Phase IV will achieve consensus on the outcomes that should be included in a final COS. ETHICS AND DISSEMINATION: The adoption of this COS into clinical and academic practice will be endorsed by the American, British and European Hernia Societies. Its utilisation in future clinical research will enable appropriate data synthesis and comparison and will enable better clinical interpretation and application of the current evidence base. This study has been registered with the Core Outcome Measures in Effectiveness Trials initiative. PROSPERO REGISTRATION NUMBER: CRD42018090084.