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.

Children and Adolescents Diagnosed With Inflammatory Bowel Disease Are at Increased Risk of Developing Diseases With a Possible Autoimmune Pathogenesis.

BACKGROUND: The development of diseases with a possible autoimmune pathogenesis is common in adults with inflammatory bowel disease (IBD). In early onset IBD, it may differ but the evidence is sparse. We aimed to investigate the risk and time span from IBD diagnosis to outcomes with different associated disorders with possible autoimmune pathogenesis. METHODS: A register-based study included all Danish patients with early onset of IBD (≤18 years) between 1980 and 2021 and 50 matched references without IBD for each case. We examined the risk of type 1 and type 2 diabetes, celiac disease, thyroid disease, rheumatoid arthritis, psoriatic arthritis, and spondyloarthritis in Cox regression models. RESULTS: In total, 6822 patients with IBD were identified, and 337 728 matched references. The median age at the time of IBD diagnosis or index date for the matched references was 16 years (25-75 percentile: 13-18 years), and the median age at the time of an outcome or at the end of follow-up was 28.1 years (25-75 percentile: 21.5-37.0 years). According to the cumulative incidence plots psoriatic arthritis, and spondyloarthritis was diagnosed approximately 10 years after the IBD onset, and the remaining outcomes later. The adjusted hazard ratio after full follow-up was 4.72 (95% CI, 3.85-5.80) for psoriatic arthritis, 5.21 (95% CI, 4.17-6.50) for spondyloarthritis, 2.77 (95% CI, 1.92-4.00) for celiac disease, 2.15 (95% CI, 1.54-3.01) for rheumatoid arthritis, 1.69 (95% CI, 1.23-2.32) and 1.64 (95% CI, 1.21-2.21) for type 1 and type 2 diabetes, respectively. For thyroid disease, it was 1.16 (95% CI, 0.97-1.40). CONCLUSIONS: The risk estimates were significantly increased for all outcomes at the end of follow-up, except for thyroid disease, but according to the cumulative incidence plots, only psoriatic arthritis and spondyloarthritis occurred earlier in the IBD cohort than in the matched references.

Children and adolescents diagnosed with inflammatory bowel disease are at increased risk of developing several diseases with possible autoimmune pathogenesis compared with a matched reference group. Cumulative incidence curves showed that psoriatic arthritis and spondyloarthritis debut in young adulthood when compared with a matched reference group without IBD.

Poly-ϵ-caprolactone scaffold as staple-line reinforcement of rectal anastomosis: an experimental piglet study.

PURPOSE: Rectal anastomoses have a persisting high incidence of anastomotic leakage. This study aimed to assess whether the use of a poly-ϵ-caprolactone (PCL) scaffold as reinforcement of a circular stapled rectal anastomosis could increase tensile strength and improve healing compared to a control in a piglet model. METHOD: Twenty weaned female piglets received a stapled rectal anastomosis and were randomised to either reinforcement with PCL scaffold (intervention) or no reinforcement (control). On postoperative day five the anastomosis was subjected to a tensile strength test followed by a histological examination to evaluate the wound healing according to the Verhofstad scoring. RESULTS: The tensile strength test showed no significant difference between the two groups, but histological evaluation revealed significant impaired wound healing in the intervention group. CONCLUSION: The incorporation of a PCL scaffold into a circular stapled rectal anastomosis did not increase anastomotic tensile strength in piglets and indicated an impaired histologically assessed wound healing.

Translation and validation of the Hirschsprung and anorectal malformation quality of life (HAQL) questionnaire in a Danish Hirschsprung population.

BACKGROUND: Hirschsprung's disease (HD) may result in an impaired quality of life (QoL) due to bowel problems, postoperative complications and other health-related issues. The Hirschsprung and Anorectal Malformation Quality of Life (HAQL) questionnaire is a disease-specific instrument developed in the Netherlands to measure the QoL in patients with HD and anorectal malformations. The aim of this study was to translate, culturally adapt and validate HAQL in a Danish Hirschsprung population. MATERIAL AND METHODS: Translation and cultural adaptation were performed according to international guidelines. Invitations to participate in the validation were sent to 401 patients operated for HD during the period from 1985 to 2012. A total of 156 patients completed the translated and culturally adapted Danish versions of HAQL and 35 parents of children and adolescents completed the corresponding parent questionnaire. Reliability was evaluated in terms of internal consistency using Cronbach's α and test-retest reliability using Intraclass Correlation Coefficient for the retest step. Known groups comparison was performed with comparison of mild HD (defined as recto-sigmoidal HD) and serious HD (defined as more proximal disease). RESULTS: The internal consistency of the dimensions was overall satisfactory for adults and adolescents but more problematic for children, where Cronbach's α was less than 0.7 in 60% of the dimensions. For both children and adolescents, the α-value was unsatisfactory for social functioning, emotional functioning, and body image. The test-retest reliability was overall good. The known groups comparison was only able to demonstrate a significant difference between mild and severe HD within one dimension. CONCLUSIONS: The translated version of the HAQL questionnaires provides an overall reliable instrument for evaluating disease-specific QoL in a Danish HD population, but it is important to acknowledge the limitations of the questionnaire, especially in children and adolescents.

Does Surgery Before Pregnancy in Women With Inflammatory Bowel Disease Increase the Risk of Adverse Maternal and Fetal Outcomes? A Danish National Cohort Study.

INTRODUCTION: Up to 15% of women with Crohn's disease (CD) or ulcerative colitis (UC) undergo bowel surgery before pregnancy, and there is little data on pregnancy outcomes in this population. We aimed to assess maternal/fetal outcomes in women with CD or UC who underwent surgeries before pregnancy. METHODS: In this nationwide study, we included all pregnancies in women with CD or UC from 1997 to 2022 and examined 6 categories of CD and UC surgeries before pregnancy. We used multilevel logistic regression to compute crude and adjusted odds ratios (aOR) with 95% confidence intervals (95% CI) for the risk of pregnancy and offspring complications in women who did, vs did not, undergo surgery before pregnancy. RESULTS: There were 833 UC and 3,150 CD pregnancies with prior surgery and 12,883 UC and CD 6,972 pregnancies without surgery. For UC, prior surgery was associated with Cesarian section (C-section) (ileoanal pouch: aOR: 20.03 [95% CI 10.33-38.83]; functional ileostomy: aOR:8.55 [6.10-11.98]; diverting ileostomy: aOR: 38.96 [17.05-89.01]) and preterm birth (aOR: 2.25 [1.48-3.75]; 3.25 [2.31-4.59]; and 2.17 [1.17-4.00]) respectively. For CD and prior intestinal surgery, the risks of C-section (aOR: 1.94 [1.66-2.27]), preterm birth (aOR: 1.30 [1.04-1.61]), and low 5-minute Apgar (aOR: 1.95 [95% CI 1.07-3.54]) increased and premature rupture of membranes (aOR: 0.68 [0.52-0.89]) decreased. For CD with only prior perianal surgery, the risk of C-section (aOR: 3.02 [2.31-3.95]) increased and risk of gestational hypertension/preeclampsia/eclampsia (aOR: 0.52 [0.30-0.89]) decreased. DISCUSSION: Providers should be aware there is an increased likelihood of C-section and certain perinatal complications in patients with CD or UC surgery before pregnancy.

Implication of Inflammatory Bowel Disease Diagnosed Before the Age of 18 for Achieving an Upper Secondary Education: A Nationwide Population-Based Cohort Study.

BACKGROUND: Educational achievement may be adversely affected by chronic conditions in childhood and adolescence. This study aimed to examine the effect of being diagnosed with IBD on achievement of an upper secondary education and the influence of disease severity and psychiatric comorbidity. METHODS: This cohort study was based on nationwide Danish administrative registries. We compared a cohort of patients with IBD with a matched population-based cohort. The IBD cohort included patients born between 1970 and 1994 who were diagnosed with IBD (age <18 years). The outcome was achieving an upper secondary education and was analyzed using Cox regression. The impact of disease severity (expressed by surgery or corticosteroid prescriptions) or psychiatric comorbidity within the IBD cohort was assessed using Poisson regression. RESULTS: We identified 3178 patients with IBD (Crohn's disease [CD] n = 1344, ulcerative colitis [UC] n = 1834) and matched them with 28 204 references. The hazard ratio of achieving an upper secondary education was 1.14 (95% confidence interval, 1.07-1.21) for CD and 1.16 (95% confidence interval, 1.10-1.23) for UC. In the IBD cohort, having surgery, a steroid prescription, or a comorbid psychiatric condition was associated with a lower chance of achieving an upper secondary education. CONCLUSION: Being diagnosed with IBD before 18 years of age increased the chance of achieving an upper secondary education. However, patients with more severe disease or psychiatric comorbidity were at higher risk of not achieving an upper secondary education than patients with milder disease.

Full-Thickness Rectal Biopsy in Children Suspected of Having Hirschsprung's Disease: The Inconclusive Biopsy.

The diagnosis of Hirschsprung's disease relies on histologically proven aganglionosis and nerve trunk hypertrophy in rectal biopsies. Although the frequency of inconclusive biopsies is relatively low, it is a relevant clinical problem. The aim of the present study was to investigate whether a re-evaluation of archived full-thickness biopsies (FTBs) stained with hematoxylin and eosin (HE), together with immune histochemical (IHC) staining, would be diagnostic in biopsies otherwise deemed inconclusive at initial examination with HE only. A total of 34 inconclusive biopsies in 31 patients were identified. From each tissue block, three slices were cut and stained with HE, S100 and calretinin. A blinded pathologist examined the tissue samples. At re-evaluation, one patient was found positive for HD and 11 negative for HD with both HE and IHC staining, respectively. In all 12 cases, the result was confirmed by the final diagnosis at a 5-year follow-up. The rest of the cases were deemed inconclusive. A re-evaluation of the remaining tissue from the biobank might have saved one third of the children from a re-biopsy. The value of adding IHC to conventional HE staining is dubious.

Preoperative intravenous iron treatment - a cohort study on colorectal cancer recurrence.

Background: Intravenous (i.v.) iron treatment has been speculated to increase the malignant potential of colorectal malignancies but also to enhance the immune systems potential to fight the invasive tumor. Clinical data however is very limited. We investigate if preoperative i.v. iron treatment is associated with colorectal cancer (CRC) recurrence. Methods: Retrospective cohort study on surgical CRC patients with iron deficiency anemia (1st March 2013 - 31st December 2019). Patients were grouped based on whether they had received preoperative treatment with i.v. iron. Local data was combined with data from the National Danish Health registries to identify recurrences, death, and emigration. Survival analysis, including Kaplan-Meyer curves and multivariate competing risk analysis adjusting for sex, age, ASA-group, tumor stage, surgical radicality, and miss match repair status was performed. Results: Of 1228 patients, 125 were available for analysis. 89 patients had received preoperative i.v. iron and 36 had not. The two groups were comparable on baseline and surgical characteristics. Median follow-up times were 4.74 in iron treated patients and 5 years in patients not receiving iron treatment. Five-year rate of non-recurrence was 85 % (0.74-0.91) in the i.v. iron treated group vs. 82 % (0.64-0.91) in the control group, non-significant difference. Multivariate survival analysis did not find iron treatment to be associated with recurrence rates (Hazard Ratio 0.88 (95 % ci; 0.31-2.51). Conclusion: No association between preoperative i.v. iron treatment and the five-year cancer recurrence rate in iron deficient anemic CRC patients was found.

Primary anastomosis and suturing combined with vacuum-assisted abdominal closure in patients with secondary peritonitis due to perforation of the small intestine: a retrospective study.

BACKGROUND: Intestinal resection and a proximal stoma is the preferred surgical approach in patients with severe secondary peritonitis due to perforation of the small intestine. However, proximal stomas may result in significant nutritional problems and long-term parenteral nutrition. This study aimed to assess whether primary anastomosis or suturing of small intestine perforation is feasible and safe using the open abdomen principle with vacuum-assisted abdominal closure (VAC). METHODS: Between January 2005 and June 2018, we performed a retrospective chart review of 20 patients (> 18 years) with diffuse faecal peritonitis caused by small intestinal perforation and treated with primary anastomosis/suturing and subsequent open abdomen with VAC. RESULTS: The median age was 65 years (range: 23-90 years). Twelve patients were female (60%). Simple suturing of the small intestinal perforation was performed in three cases and intestinal resection with primary anastomosis in 17 cases. Four patients (20%) died within 90-days postoperatively. Leakage occurred in five cases (25%), and three patients developed an enteroatmospheric fistula (15%). Thirteen of 16 patients (83%) who survived were discharged without a stoma. The rest had a permanent stoma. CONCLUSIONS: Primary suturing or resection with anastomosis and open abdomen with VAC in small intestinal perforation with severe faecal peritonitis is associated with a high rate of leakage and enteroatmospheric fistula formation. TRIAL REGISTRATION: The study was approved by the Danish Patient Safety Authority (case number 3-3013-1555/1) and the Danish Data Protection Agency (file number 18/28,404). No funding was received.

Watchful Waiting After Radiological Guided Drainage of Intra-abdominal Abscess in Patients With Crohn's Disease Might Be Associated With Increased Rates of Stoma Construction.

Background: Management of spontaneous intra-abdominal abscess (IAA) in patients with Crohn's disease (CD) with radiologically guided percutaneous drainage (PD) was debated. Methods: This is a secondary analysis from a multicenter, retrospective cohort study of all the patients with CD who underwent PD followed by surgery at 19 international tertiary centers. Results: Seventeen patients (4.8%) who did not undergo surgery after PD were compared to those who had PD followed by surgical intervention 335/352 (95.2%). Patients who had PD without surgery were those with longer disease duration, more frequently had previous surgery for CD (laparotomies/laparoscopies), enteric fistula, on steroid treatment before and continue to have it after PD. Patients who had PD without subsequent surgical resection had a higher risk of stoma construction at later stages 8/17 (47.1%) versus 90/326 (27.6%) (P < .01). Patients with PD with no subsequent surgery had numerically higher rates of abscess recurrence 5/17 (29.4%) compared to those who had PD followed by surgery 45/335 (13.4%) the difference was not statistically significant (P = .07). Conclusions: Even with the low number of patients enrolled in this study who had PD of IAA without subsequent surgery, the findings indicate a markedly worse prognosis in terms of recurrence, length of stay, readmission, and stoma construction. Watchful waiting after PD to treat patients with spontaneous IAA might be indicated in selected patients with poor health status or poor prognostic factors.

A population-based nationwide study on total colectomy for ulcerative colitis and risk of ten prevalent inflammatory or autoimmune diseases.

BACKGROUND: There is growing evidence to support a role of the gut microbiome in the development of chronic inflammatory and autoimmune disease (IAD). We used total colectomy (TC) for ulcerative colitis (UC) as a model for a significant disruption in gut microbiome to explore an association with subsequent risk of IAD. METHODS: We identified all patients with UC and no diagnosis of IAD prior to their UC diagnosis in Denmark from 1988 to 2015. Patients were followed from the date of UC to a diagnosis of IAD, death or end of follow-up, whichever occurred first. We used Cox regression to estimate hazard ratios (HRs) of IAD associated with TC, adjusting for age, sex, Charlson Comorbidity Index, and calendar year of UC diagnosis. RESULTS: 30,507 patients with UC (3,155 with TC and 27,352 without) were identified from the Danish National Patient Registry. During 43,266 person-years of follow-up, 2733 patients were diagnosed with an IAD. The risk of any IAD was higher for patients with TC compared to patients without (adjusted HR [aHR] 1.39 (95% CI: 1.24-1.57)). When the analyses were adjusted for exposure to antibiotics, immunomodulatory medicine and biologics (covering 2005-2018), the risk of IAD was still higher for patients with total colectomy (aHR = 1.41 (95% CI: 1.09;1.83)). Disease-specific analyses were weakened by a low number of outcomes. CONCLUSIONS: The risk of IAD was higher for patients who underwent TC for UC compared to patients who did not.KEY MESSAGESWhat is already known?o The gut microbiome plays an important role in host immune homeostasis, and changes in gut bacterial diversity and composition may change the individual's risk of inflammatory and autoimmune disease (IAD).What is new here?o Patients with ulcerative colitis who undergo total colectomy have a higher risk of being diagnosed with IAD, compared to patients with ulcerative colitis who do not undergo total colectomy.How can this study help patient care?o Future research can help uncover the mechanisms responsible for the higher risk of certain IADs after total colectomy. If the microbiome plays a role, modifying the gut microbiome could prove a viable therapeutic strategy to reduce the risk of developing IADs.

In this nationwide Danish cohort study of all Danish UC patients diagnosed in the period from 1988 to 2015, the risk of being diagnosed with inflammatory and autoimmune disease is higher for patients who underwent total colectomy compared to UC patients without total colectomy.

Whole genome sequencing and disease pattern in patients with juvenile polyposis syndrome: a nationwide study.

Juvenile polyposis syndrome (JPS) is a hereditary hamartomatous polyposis syndrome characterized by gastrointestinal juvenile polyps and increased risk of gastrointestinal cancer. Germline pathogenic variants are detected in SMAD4 or BMPR1A, however in a significant number of patients with JPS, the etiology is unknown. From Danish registers, and genetic department and laboratories, we identified all patients in Denmark with a clinical diagnosis of JPS and/or a pathogenic variant in BMPR1A or SMAD4. In patients where no variant had been detected, we performed genetic analysis, including whole genome sequencing. We collected clinical information on all patients to investigate the phenotypic spectrum. Sixty-six patients (mean age 40 years) were included of whom the pathogenic variant was unknown in seven patients. We detected a pathogenic variant in SMAD4 or PTEN in additional three patients and thus ≈ 95% of patients had a pathogenic germline variant. Endoscopic information was available in fifty-two patients (79%) and of these 31 (60%) fulfilled the clinical criteria of JPS. In 41 patients (79%), other types of polyps than juvenile had been removed. Our results suggest that almost all patients with a clinical diagnosis of JPS has a pathogenic variant in mainly BMPR1A, SMAD4, and more rarely PTEN. However, not all patients with a pathogenic variant fulfil the clinical criteria of JPS. We also demonstrated a wide clinical spectrum, and that the histopathology of removed polyps varied.

Early versus late reversal of diverting loop ileostomy in rectal cancer surgery: a multicentre randomized controlled trial.

Diverting loop ileostomy has become routine in low anterior resection (LAR) for rectal cancer. The optimal time for stoma reversal is controversial. The aim of the present study was to compare the results after planned early (within 8-12 days) versus late (> 3 months) stoma reversal. The primary outcomes were morbidity and mortality, as measured by the Comprehensive Complication Index (CCI) within 30 days after stoma reversal, and the secondary outcomes were morbidity and mortality within 90 days after LAR. This was a multicentre trial including all patients scheduled for anterior low resection for rectal cancer with curative intent. Inclusion period was from April 2011 to December 2018. All patients were randomized 1:1 prior to surgery. Among 257 consecutive and eligible patients, a total of 214 patients were randomized: 107 patients to early stoma reversal and 107 to late reversal. A total of 68 patients were excluded for various reasons, and 146 patients completed the study, with 77 in the early reversal group and 69 in the late reversal group. The patients were asked to complete the Gastrointestinal Quality of Life Index before surgery (baseline) and at 6 and 12 months after LAR. Ostomy-related complications were evaluated by dedicated ostomy staff using the validated DET score. ClinicalTrials Identifier: NCT01865071. Fifty-three patients (69%) in the early reversal group and 60 patients (87%) in the late reversal group received the intended treatment. There were no significant differences in CCI within 90 days after index surgery with the LAR and within 30 days after stoma reversal between the two groups. There were no differences in patient-reported quality of life but significantly more stoma-related complications in the late reversal group. A total of 5 patients experienced anastomotic leakage (AL) after stoma reversal, 4 in the early reversal group and one in the late reversal group. Early and late stoma reversal showed similar outcomes in terms of overall complications and quality of life. The risk of developing anastomotic leakage after early ostomy reversal is a concern.

Survival, surveillance, and genetics in patients with Peutz-Jeghers syndrome: A nationwide study.

Peutz-Jeghers syndrome (PJS) is an autosomal dominant hereditary polyposis syndrome causing increased morbidity and mortality due to complications of polyposis and the development of cancer. STK11 is the only gene known to be associated with PJS, although in 10%-15% of patients fulfilling the diagnostic criteria no pathogenic variant (PV) is identified. The primary aim of this study was to identify the genetic etiology in all known PJS patients in Denmark and to estimate the risk of cancer, effect of surveillance and overall survival. We identified 56 patients (2-83 years old) with PJS. The detection rate of PVs was 96%, including three cases of mosaicism (6%). In two patients a variant was not detected. At the age of 40 years, the probabilities of cancer and death were 21% and 16%, respectively; at the age of 70 years these probabilities were 71% and 69%. Most cases of cancer (92%) were identified between the scheduled examinations in the surveillance program. These observations emphasize that PJS should be regarded as a general cancer predisposition syndrome, where improvement of clinical care is needed.

Early Pre- and Postoperative Enteral Nutrition and Growth in Infants with Symptomatic Congenital Diaphragmatic Hernia.

OBJECTIVES: Nutritional support during the neonatal and postoperative period in congenital diaphragmatic hernia (CDH) is challenging and controversial. We aimed to report on early enteral nutritional support in symptomatic CDH patients during the pre- and postoperative period, including feasibility, associated factors with established full enteral nutrition, and weight at birth, discharge, and 18 months. METHODS: We retrospectively collected data on nutrition: type and volume of enteral nutrition and parental support. Enteral feeding was introduced preoperatively from day 1 after birth, increased step-wised (breastmilk preferred), and resumed after CDH repair on the first postoperative day. Baseline data were available from our CDH database. RESULTS: From 2011 to 2020, we identified 45 CDH infants. Twenty-two were girls (51.1%), 35 left sided (77.8%), and 40 underwent CDH repair (88.9%). Median (interquartile range) length of stay in the pediatric intensive care unit was 14.6 days (6.0-26.5), and 1-year mortality was 17.8%.Postoperatively, 120 and 160 mL/kg/d of enteral nutrition was achieved after a median of 6.5 (3.6-12.6) and 10.6 (7.6-21.7) days, respectively. In total, 31 (68.9%) needed supplemental parenteral nutrition in a median period of 8 days (5-18), and of those 11 had parenteral nutrition initiated before CDH repair. No complications to enteral feeding were reported. CONCLUSION: Early enteral nutrition in CDH infants is feasible and may have the potential to reduce the need for parental nutrition and reduce time to full enteral nutrition in the postoperative period.

Bowel Control, Bladder Function, and Quality of Life in Children with Cloacal Malformations.

INTRODUCTION: Long-term outcomes of cloacal malformations remain unclear. We evaluated postoperative bowel control, bladder function and quality of life in patients under 18 years of age with cloaca. MATERIALS AND METHODS: This was a multi-center cross-sectional observational study accomplished by the Nordic Pediatric Surgery Research Consortium. Patients with a cloacal malformation, 4-17 years of age, were eligible. Data including patient characteristics, surgical procedures, and complications were retrieved from case records. Established questionnaires with normative control values evaluating bowel function, bladder function, and health-related quality of life (HRQoL) were sent to the patients and their caregivers. The study was approved by the participating center's Ethics Review Authorities. RESULTS: Twenty-six (67%) of 39 eligible patients with median age 9.5 (range, 4-17) years responded. Twenty-one (81%) patients had a common channel ≤3 cm. Imaging confirmed sacral anomalies in 11 patients and spinal cord abnormalities in nine. Excluding patients with stoma (n = 5), median bowel function score was 12 [7-19], and 5 patients (20%) reported a bowel function score ≥17, approaching normal bowel control level. Bowel management increased proportion of socially continent school-aged children to 52%. Six (23%) patients had a permanent urinary diversion or used clean intermittent catheterization (CIC), while majority (70%) of the remaining patients were urinary continent. The reported HRQoL was comparable to healthy Swedish children. CONCLUSION: Whilst well-preserved spontaneous bowel control was rare, a majority of patients were dry for urine without any additional procedures. Few patients experienced social problems or negative impact on HRQoL due to bladder or bowel dysfunction. LEVEL OF EVIDENCE: Level IV.

Anastomotic perfusion assessment with indocyanine green in robot-assisted low-anterior resection, a multicenter study of interobserver variation.

BACKGROUND: Securing sufficient blood perfusion to the anastomotic area after low-anterior resection is a crucial factor in preventing anastomotic leakage (AL). Intra-operative indocyanine green fluorescent imaging (ICG-FI) has been suggested as a tool to assess perfusion. However, knowledge of inter-observer variation among surgeons in the interpretation of ICG-FI is sparse. Our primary objective was to evaluate inter-observer variation among surgeons in the interpretation of bowel blood-perfusion assessed visually by ICG-FI. Our secondary objective was to compare the results both from the visual assessment of ICG and from computer-based quantitative analyses of ICG-FI between patients with and without the development of AL. METHOD: A multicenter study, including patients undergoing robot-assisted low anterior resection with stapled anastomosis. ICG-FI was evaluated visually by the surgeon intra-operatively. Postoperatively, recorded videos were anonymized and exchanged between centers for inter-observer evaluation. Time to visibility (TTV), time to maximum visibility (TMV), and time to wash-out (TWO) were visually assessed. In addition, the ICG-FI video-recordings were analyzed using validated pixel analysis software to quantify blood perfusion. RESULTS: Fifty-five patients were included, and five developed clinical AL. Bland-Altman plots (BA plots) demonstrated wide inter-observer variation for visually assessed fluorescence on all parameters (TTV, TMV, and TWO). Comparing leak-group with no-leak group, we found no significant differences for TTV: Hazard Ratio; HR = 0.82 (CI 0.32; 2.08), TMV: HR = 0.62 (CI 0.24; 1.59), or TWO: HR = 1.11 (CI 0.40; 3.11). In the quantitative pixel analysis, a lower slope of the fluorescence time-curve was found in patients with a subsequent leak: median 0.08 (0.07;0.10) compared with non-leak patients: median 0.13 (0.10;0.17) (p = 0.04). CONCLUSION: The surgeon's visual assessment of the ICG-FI demonstrated wide inter-observer variation, there were no differences between patients with and without AL. However, quantitative pixel analysis showed a significant difference between groups. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04766060.

Extended Right-Sided Colon Resection Does Not Reduce the Risk of Colon Cancer Local-Regional Recurrence: Nationwide Population-Based Study From Danish Colorectal Cancer Group Database.

BACKGROUND: It is controversial whether extensive resection of right-sided colon cancer confers oncological benefits. OBJECTIVE: The aim of this study was to evaluate short- and long-term outcomes of extended surgical removal of the mesocolon compared to the conventional approach. DESIGN: This was a retrospective population-based study. SETTING: Study is based on a prospectively maintained Danish Colorectal Cancer Group database. MAIN OUTCOME MEASURES: Primary outcome measures included local-regional recurrence in patients who underwent curative resection for right-sided colon cancer and 30-day postoperative complications. Distant metastasis, unplanned intraoperative adverse events, and 30- and 90-day postoperative mortality were also investigated. Patients who had palliative or compromised resection, emergency surgery, or neoadjuvant chemotherapy were excluded. RESULTS: Of the 12,855 patients with resection of right-sided colon cancer retrieved, 1151 underwent extended right hemicolectomy. Patients who had extended right hemicolectomy were younger males with lower ASA scores, were operated on by colorectal surgeons using a laparoscopic approach, and had a significantly higher number of harvested lymph nodes. The rate of local-regional recurrence was 1.1% (136/12,855), with no difference between conventional right hemicolectomy and extended right hemicolectomy (OR, 1.7; 95% CI, 0.63-2.18). Postoperative medical complications were significantly higher in extended right hemicolectomy even after adjusting for age, comorbidity, access to the abdomen, and other covariates (OR, 1.26; 95% CI, 1.01-1.58). No significant difference was noticed between conventional right hemicolectomy and extended right hemicolectomy in the rates of distant metastasis, unplanned intraoperative adverse events, and mortality. LIMITATIONS: Because it is a register-based study, underreporting cannot be excluded. Extended right hemicolectomy, as defined in this study, does not reflect the extent of lymphatic dissection performed during the surgery. CONCLUSIONS: This large population-based register study showed no difference in local-regional recurrence of right-sided colon cancer between conventional and extended right hemicolectomy with mesenteric resection and ligation of the middle colic vessels. Extended resection was associated with higher rates of postoperative complications. See Video Abstract at http://links.lww.com/DCR/B907 . LA RESECCIN AMPLIADA DEL COLON DERECHO NO REDUCE EL RIESGO DE RECURRENCIA LOCALREGIONAL DEL CNCER DE COLON ESTUDIO POBLACIONAL A NIVEL NACIONAL DE LA BASE DE DATOS DEL GRUPO DANS DE CNCER COLORRECTAL: ANTECEDENTES:Es aun un tema controversial si la resección ampliada del cáncer de colon del lado derecho confiere beneficios oncológicos.OBJETIVOS:El objetivo de este estudio fue examinar los resultados a corto y largo plazo de la resección quirúrgica ampliada del mesocolon en comparación con el enfoque convencional.DISEÑO:Este fue un estudio poblacional de tipo retrospectivo basado en una base de datos del Grupo Danés de Cáncer Colorrectal mantenida de manera prospectiva.AJUSTES:La medida de resultado primaria fue la recurrencia local-regional en pacientes sometidos a resección curativa por cáncer de colon del lado derecho y las medidas de resultado secundarias fueron las complicaciones posoperatorias a los 30 días. También fueron investigadas las metástasis a distancia, los eventos adversos intraoperatorios no planificados y la mortalidad posoperatoria a los 30 y 90 días. Se excluyeron los pacientes sometidos a resección paliativa o comprometida, cirugía de urgencia y quimioterapia neoadyuvante.RESULTADOS:De los 12.855 pacientes recuperados y sometidos a resección de cáncer de colon del lado derecho, 1151 fueron sometidos a hemicolectomía derecha ampliada. Los pacientes sometidos a hemicolectomía derecha ampliada fueron varones más jóvenes con puntuaciones ASA más bajas, operados por cirujanos colorrectales, utilizando la vía laparoscópica, y tuvieron un número significativamente mayor de ganglios linfáticos extraídos. La tasa de recidiva local-regional fue del 1,1% (136 / 12.855) sin diferencia entre la hemicolectomía derecha convencional y la hemicolectomía derecha ampliada (OR 1,7 IC 95% 0,63-2,18). Las complicaciones médicas post operatorias fueron significativamente mayores en la hemicolectomía derecha ampliada incluso después del ajuste por edad, comorbilidad, acceso al abdomen y otras covariables (OR 1,26; IC 95% 1,01-1,58). No se observaron diferencias significativas entre la hemicolectomía derecha convencional y la hemicolectomía derecha ampliada con respecto a las tasas de metástasis a distancia, eventos adversos intraoperatorios no planificados y mortalidad.LIMITACIONES:Es un estudio basado en registros, por lo tanto, no se puede excluir la sub notificación. La hemicolectomía derecha ampliada como se define en este estudio no refleja la extensión de la disección linfática realizada durante la cirugía.CONCLUSIONES:Este gran estudio basado en el registro poblacional no mostró diferencias en la recurrencia local-regional del cáncer de colon del lado derecho entre la hemicolectomía derecha convencional y ampliada con resección mesentérica y ligadura de los vasos cólicos medios. La resección ampliada se asoció con tasas más altas de complicaciones posoperatorias. Consulte Video Resumen en http://links.lww.com/DCR/B907 . (Traducción-Dr. Osvaldo Gauto ).

Distinct gastric phenotype in patients with pathogenic variants in SMAD4: A nationwide cross-sectional study.

Background and study aims In most patients with juvenile polyposis Syndrome, it is possible to detect a pathogenic germline variant in SMAD4 or BMPR1A . It is well known that patients with a pathogenic variant in SMAD4 have a higher risk of gastric polyposis and gastric cancer compared to BMPR1A carriers, but the natural history of gastric involvement is poorly described. We aimed to systematically review endoscopic and histopathological gastric findings in Danish patients with pathogenic variants in SMAD4. Patients and methods This was a retrospective, cross-sectional study including endoscopic and histological gastric findings in all known Danish patients with pathogenic variants in SMAD4 . The patients were identified by data from various registries as well as from clinical genetic departments and laboratories. Results We identified 41 patients (2-72 years) with a pathogenic SMAD4 variant . In 31 patients, we were able to retrieve information on upper gastrointestinal endoscopy. Eighty-seven percent had at least one gastric abnormality including erythema (72 %) and edema (72 %). Half of the patients also had vulnerability of the mucosa and 68 % had gastric polyposis. An increasing frequency of abnormalities were observed with increasing age. Gastric cancer was diagnosed in 5 % of the cases and 22 % had a gastrectomy mainly because of massive polyposis. Conclusions This study showed that most patients with pathogenic SMAD4 variants have a distinct phenotype of the gastric mucosa, and with an increasing severity in the elderly patients. These findings provide new insights into the natural history of gastric manifestations in patients with pathogenic SMAD4 variants.