Should primary anastomosis be considered more? A retrospective analysis of anastomotic complications in young children.

Objective: Little is known about intestinal anastomotic leakage and stenosis in young children (≤3 years of age). The purpose of this study is to answer the following questions: (1) what is the incidence of anastomotic stenosis and leakage in infants? (2) which surgical diseases entail the highest incidence of anastomotic stenosis and leakage? (3) what are perioperative factors associated with anastomotic stenosis and leakage? Methods: Patients who underwent an intestinal anastomosis during primary abdominal surgery in our tertiary referral centre between 1998 and 2018 were retrospectively included. Both general incidence and incidence per disease of anastomotic complications were determined. Technical risk factors (location and type of anastomosis, mode of suturing, and suture resorption time) were evaluated by multivariate Cox regression for anastomotic stenosis. Gender and American Society of Anaesthesiology (ASA) score of ≥III were evaluated by χ2 test for anastomotic leakage. Results: In total, 477 patients underwent an anastomosis. The most prominent diseases are intestinal atresia (30%), Hirschsprung's disease (29%), and necrotizing enterocolitis (14%). Anastomotic stenosis developed in 7% (34/468) of the patients with highest occurrence in necrotizing enterocolitis (14%, 9/65). Colonic anastomosis was associated with an increased risk of anastomotic stenosis (hazard ratio (HR) =3.6, 95% CI 1.8 to 7.5). No technical features (type of anastomosis, suture resorption time and mode of suturing) were significantly associated with stenosis development. Anastomotic leakage developed in 5% (22/477) of the patients, with the highest occurrence in patients with intestinal atresia (6%, 9/143). An ASA score of ≥III (p=0.03) and male gender (p=0.03) were significantly associated with anastomotic leakage. Conclusions: Both anastomotic stenosis and leakage are major surgical complications. Identifying more patient specific factors can result in better treatment selection, which should not solely be based on the type of disease.

Routine contrast enema prior to stoma reversal seems only required following treatment for necrotizing enterocolitis: An evaluation of the diagnostic accuracy of the contrast enema.

INTRODUCTION: Contrast enemas are often made prior to stoma reversal in order to detect distal intestinal strictures distal of the stoma. If untreated these strictures can cause obstruction which might necessitate redo-surgery. However, the value of contrast enemas is unclear. Therefore, we aim to evaluate the contrast enema's diagnostic accuracy in detecting strictures in children with a stoma. METHODS: Young children (≤3 years) treated with a stoma between 1998 and 2018 were retrospectively included. The STARD criteria were followed. Patients treated for anorectal malformations and those that died before stoma reversal were excluded. Surgical identification of strictures during reversal or redo-surgery within three months was used as gold standard. Sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) and area under the curve (AUC) reflected diagnostic accuracy. RESULTS: In 224 included children, strictures were found during reversal in 10% of which 95% in patients treated for necrotizing enterocolitis. Contrast enema was performed in 68% of all patients and detected 92% of the strictures. In the overall cohort, the sensitivity was 100%, specificity 98%, PPV 88% and NPV 100% whilst the AUC was 0.98. In patients treated for NEC, the sensitivity was 100%, specificity 97%, PPV 88% and NPV 100% whilst the AUC was 0.98. CONCLUSION: Strictures prior to stoma reversal seem to be mainly identified in patients treated for NEC and not in other diseases necessitating a stoma. Moreover, the contrast enema shows excellent diagnostic accuracy in detecting these strictures. For this reason we advise to only perform contrast enemas in patients treated for NEC. LEVEL OF EVIDENCE: II.

Age-specific and family-centered information modalities to prepare children at home for day-care surgery.

BACKGROUND: Surgery induced stress and anxiety in children and parents can be reduced by providing preoperative information adapted to their needs. Aim of this study was to evaluate the effects of three different information modalities (coloring page, mobile application and videos) to prepare children and their parents for day-care surgery on preoperative anxiety and postoperative pain experienced by the child, and preoperative anxiety and satisfaction of parents. METHODS: Prospective observational study including children and their parents that were offered specifically developed information modalities to prepare for day-care surgery. Results were compared between children and their parents that used none (i.e., control group) versus one or more information modalities (i.e., intervention group). Primary outcomes were preoperative anxiety measured using PROMIS v2.0 Anxiety and postoperative pain in children. Secondary outcomes were preoperative parental anxiety (STAI questionnaire) and family satisfaction with information and communication (modified PedsQL Healthcare Satisfaction questionnaire). Subgroup analyses were performed between preschoolers (0-5 years) and school-aged (≥5) children. RESULTS: 93 patients (male 53%) were included in the intervention (n=56) and control group (n=37). Levels of children's preoperative anxiety and postoperative pain, and parental anxiety did not differ between both groups. Families of prepared children were more satisfied with information and communication about preoperative surgical information (8 vs. 6.6, p=0.004) and satisfaction with how parents (7 vs 8, p=0.019) and children (8 vs 6, p=0.018) were prepared for surgery. CONCLUSIONS: Preoperative anxiety did not differ between prepared and unprepared children. The use of specifically developed family-centered and age-appropriate information modalities to prepare children for day-care surgery at home results in superior family satisfaction. LEVEL OF EVIDENCE: III.

Diagnostic accuracy of palpation and ultrasonography for diagnosing infantile hypertrophic pyloric stenosis: a systematic review and meta-analysis.

OBJECTIVE: Although infantile hypertrophic pyloric stenosis (IHPS) is a well-known disease, there is no systematic review regarding the optimal diagnostic strategy. We conducted a systematic review and meta-analysis to obtain diagnostic accuracy of all methods to diagnose IHPS. METHODS: According to the Preferred Reported Items for Systematic Reviews and Meta-Analysis guidelines, we searched MEDLINE and Embase to identify studies reporting sensitivity and specificity of all methods used to diagnose IHPS. Inclusion criteria were infants with suspicion of/or diagnosed with IHPS who underwent pyloromyotomy or had clinical follow-up. A random-effects model was used to obtain pooled estimates of sensitivity, specificity and area under the receiver operating characteristic curve. RESULTS: After screening 5364 studies, we included 43 studies with in total 6085 infants (n = 4241 IHPS; n = 1844 controls). The diagnostic sensitivity of palpation ranged from 10.0 to 93.4% and decreased over time. Different parameters for ultrasonography were found. Most used parameters were pyloric muscle thickness (PMT) ≥ 3 mm (pooled sensitivity 97.6% and specificity 98.8%), PMT ≥ 4 mm (pooled sensitivity 94.0% and specificity 98.0%) or a combination of PMT ≥ 4 mm and/or pyloric canal length ≥16 mm (pooled sensitivity 94.0% and specificity 91.7%). The AUC showed high diagnostic accuracy (0.997, 0.966 and 0.981 respectively), but large heterogeneity exists. Due to the large differences in cut-off values no meta-analysis could be conducted for pyloric canal length and pyloric diameter. CONCLUSION: Palpation has limited sensitivity in diagnosing IHPS. We showed that ultrasonography has highest diagnostic accuracy to diagnose IHPS and we advise to use PMT ≥ 3 mm as cut-off. ADVANCES IN KNOWLEDGE: This is the first systematic review and meta-analysis on diagnosing IHPS, which summarizes the available literature and may be used as a guideline.

Generic and disease-specific health-related quality of life in patients with Hirschsprung disease: A systematic review and meta-analysis.

BACKGROUND: Patients with Hirschsprung disease (HD) are at risk of persistent constipation, fecal incontinence or recurrent enterocolitis after surgical treatment, which in turn may impact physical and psychosocial functioning. Generic health-related quality of life (HRQoL) and disease-specific health-related quality of life are relevant outcome measures to assess the impact of HD on the QoL of these patients. AIM: To summarize all available evidence on HRQoL of patients with HD after surgery and the impact of possible moderating factors. METHODS: Pubmed, Web of Sciences, PsycInfo and Embase were searched with search terms related to 'Hirschsprung disease', 'Pediatrics' and 'Quality of life'. Mean and standard deviation of generic HRQoL overall and domain scores were extracted from each study, as well as data describing potential factors associated with QoL. Random effect models were used for meta-analytic aggregation of generic HRQoL scores. Meta-regression was used to assess the relationship between patient and clinical characteristics and generic HRQoL. Disease-specific HRQoL outcomes of patients with HD were systematically reviewed. RESULTS: Seventeen articles were included in the systematic review (n = 1137 patients) and 15 in the quantitative meta-analysis (n = 1024 patients). Four studies reported disease-specific HRQoL. Patient's age ranged between 0 and 21 years. Meta-analytic aggregation showed a non-significantly impaired generic HRQoL (d = -0.168 [95%CI: -0.481; 0.145], P = 0.293, I 2 = 94.9) in patients with HD compared to healthy controls. Physical (d = -0.042 [95%CI: -0.419; 0.335], P = 0.829, I 2 = 95.1), psychosocial (d = -0.159 [95%CI: -0.458; 0.141], P = 0.299, I 2 = 93.6) and social HRQoL (d = -0.092 [95%CI: -0.642; 0.457], P = 0.742, I² = 92.3) were also not significantly lower compared to healthy controls. There was no relation between health-related outcomes and the sex of the patients and whether generic HRQoL was measured by parental proxy or self-report. Disease-specific complaints of patients with HD impaired physical HRQoL, but not psychosocial and social HRQoL. CONCLUSION: In this systematic review and meta-analysis, no evidence was found for impaired generic HRQoL in patients with HD compared to healthy controls, neither for moderating effects of sex, parental proxy or self-report.

Adhesive small bowel obstruction following abdominal surgery in young children (≤ 3 years): A retrospective analysis of incidence and risk factors using multivariate cox regression.

BACKGROUND: Adhesions following abdominal surgery can cause small bowel obstruction (SBO) necessitating surgery. Whilst some studies have addressed SBO in children, the incidence of SBO, the diseases that are of increased risk as well as risk factors in young children remain unclear. Therefore, this study aims to determine; (1) the general incidence of SBO in young children, (2) which diseases entail highest incidence of SBO and (3) risk factors for SBO in young children. STUDY DESIGN: Young children (≤ 3 years of age) who underwent abdominal surgery in our tertiary referral centre between 1998-2018 were retrospectively included. Both general incidence and incidence per disease of SBO were determined. Independent risk factors for SBO were identified using cox-regression. RESULTS: The incidence of SBO was 5% (N = 88/1931) in our cohort. Five of the SBOs developed following laparoscopic treatment. Patients treated for gastroschisis (17%,N = 9/53), necrotizing enterocolitis (8%,N = 15/188) and intestinal atresia (7%,N = 13/177) were at high risk of experiencing SBO. Diaphragmatic hernia (28%,N = 7/25) and meconium ileus (28%,N = 7/25) also showed high SBO proportions. Having a history of stoma (HR:3.2, 95%-CI:2.0-5.2), undergoing emergency surgery (HR:2.2, 95%-CI:1.3-3.7) and postoperative infections (HR:1.9, 95%-CI:1.2-3.1) were general risk factors for the development of SBO. CONCLUSION: The incidence of SBO in young children seems higher than what has previously been reported in older children, which is why they should be studied separately. The incidence of SBO differs between diseases. Having a history of a stoma, emergency surgery and postoperative infections were independent risk factors for SBO development. Although less at risk, SBOs do develop after laparoscopies, which is why they should be included in more long-term follow-up studies. LEVEL OF EVIDENCE: II.

Treatment of jejunoileal atresia by primary anastomosis or enterostomy: Double the operations, double the risk of complications.

PURPOSE: No study has evaluated complication rates of the combined operations needed for temporary Enterostomy compared to primary anastomosis in the treatment of Jejunoileal Atresia. Therefore the aim of this study is: 1) to compare the occurrence of severe postoperative complications (defined as Clavien-Dindo ≥III within 30 days) and 2) to compare the occurrence of different short- and long-term complications following treatment for Jejunoileal atresia either by primary anastomosis or the combined Enterostomy procedures. METHODS: All consecutive neonates treated for Jejunoileal Atresias between January 1998 and February 2021 at our tertiary academic centres were retrospectively included. Perioperative characteristics and severity of postoperative complications (Clavien-Dindo) were extracted and evaluated, using chi-squared statistics, following each operation per treatment. RESULTS: Eighty patients were included of whom 48 (60%) received a primary anastomosis and 32 (40%) an Enterostomy. Perioperative baseline characteristics were comparable, apart from significantly more patients with a gastroschisis and significantly less patients with jejunum atresia in the Enterostomy group. Our results showed that 1) significantly (p ≤ 0.01) more CD ≥III occur following treatment by Enterostomy. 2) Both short-term (surgical site infection, wound dehiscence) and long-term (short bowel syndrome, adhesive bowel obstruction) complications occurred significantly more in those treated by Enterostomy. We showed no significant difference in anastomotic leakage/stenosis and mortality rates between both treatment strategies. CONCLUSION: Although perioperative factors might necessitate an Enterostomy, we advise a low threshold for performing a primary anastomosis when in doubt, taking into account the double risk of major complications found in patients treated with a temporary Enterostomy.

Incisional hernia after abdominal surgery in infants: A retrospective analysis of incidence and risk factors.

PURPOSE: Incisional hernia (IH) is a complication following abdominal surgery extensively studied in adults but less so in infants. This study aimed to identify the incidence, high risk diseases and risk factors of IH following abdominal surgery in infants. METHODS: Infants undergoing abdominal surgery before the age of three years in our tertiary centre between 1998 and 2018 were included. Patient demographics, peri­operative details and the course during follow up were retrospectively extracted from patient records. Multivariate logistic regression was performed to identify risk factors. RESULTS: The incidence of incisional hernia was 5.2% (107/2055). Necrotizing enterocolitis (12%), gastroschisis (19%), and omphalocele (17%) had the highest incidences of IH. Wound infection (OR: 5.3, 95%-CI:2.9-9.5), preterm birth (OR: 4.2, 95%-CI:2.6-6.7) and history of stoma (OR 1.7, 95%-CI:1.1-2.8) were significant risk factors for IH. Whilst age at surgery, surgical approach and total number of operations did not significantly influence IH development. The IH resolved in 15% (16/107) without surgery. CONCLUSION: One in twenty infants experiences IH following abdominal surgery, which is higher than previously described. Understanding the incidence of IH and associated risk factors will allow physicians to identify infants that may be at increased risk for IH and to possibly act pre-emptively.

Incisional hernia after surgical correction of abdominal congenital anomalies in infants: a systematic review with meta-analysis.

Incisional hernia (IH) in children could result in life-threatening complications, including incarceration and bowel strangulation. The incidence and risk factors of IH in infants are scarcely reported. Since IH-correction may require extensive surgery and a long recovery program, identifying infants and birth defects at risk, may lead to a different approach during the primary surgery. Therefore, the aim of this review is to systematically review the available data on the incidence of IH following surgery for congenital anomalies in infants. All studies describing IH were considered eligible. PubMed and Embase were searched and risk of bias was assessed. Primary outcome was the incidence of IH, secondary outcomes were difference in IH occurrence between disease severity (complex vs simple) and closure method (SILO vs primary closure) in gastroschisis patients. A meta-analysis was performed to pool the reported incidences in total and per congenital anomaly separately. Subgroup analysis within gastroschisis articles was performed. The 50 included studies represent 3140 patients. The pooled proportion of IH was 0.03 (95% CI 0.02-0.05; I2 = 79%, p ≤ 0.01) all anomalies combined. Gastroschisis (GS) reported highest pooled proportion 0.10 (95% CI 0.06-0.17; n = 142/1273; I2 = 86%; p ≤ 0.01). SILO closure (OR 3.09) and simple gastroschisis, i.e. without additional anomalies, (OR 0.18) were of significant influence. This review reports the incidence of IH in infants with different congenital abdominal anomalies, of which gastroschisis reported the highest risk. In GS patients, complex GS and SILO closure are risk factors for IH development.

Consensus on the definition of colorectal anastomotic leakage: A modified Delphi study.

BACKGROUND: Despite the emerging knowledge about colorectal anastomotic leakage (CAL) through the increasing number of clinical and experimental studies, there is no generally accepted definition of CAL. Because of the wide variety of definitions used in literature, comparison of study outcomes and quality of care is complicated. AIM: To reach consensus on the definition of CAL using a modified Delphi method. METHODS: The RAND/UCLA appropriateness method was used. The expert panel consisted of international colorectal surgeons and researchers who had published three or more articles about CAL. The consensus process consisted of two online distributed questionnaires and a third round with a recommendation. In the questionnaires participants were asked to rate the appropriateness of statements using a 1-9 Likert scale. Consensus was defined as a panel median between 1-3 or 7-9 without disagreement. In the final round a recommendation was formed regarding the definition of CAL and the expert panel was asked if they agreed or disagreed. RESULTS: Twenty-three authors participated in the first round and twenty-one finished the second round. After two rounds consensus was reached on 37 items (80%) in nine different categories. The International Study Group of Rectal Cancer definition is the most frequently advised general definition by our panel. Consensus was reached regarding the clinical symptoms of CAL, which serum markers contributes to the suspicion of CAL, which radiological and perioperative findings should be considered as CAL, which grading system is appropriate and if there should be a range of postoperative days in the definition. Eventually, 19 experts completed all three rounds of which 16 (84%) agreed with our final recommendations for the definition of CAL. CONCLUSION: A consensus-based recommendation for the definition of CAL was formed using our modified Delphi method that can be widely incorporated in the field.

Inguinal hernia in girls: A retrospective analysis of over 1000 patients.

BACKGROUND: In girls with inguinal hernia, timing of surgical repair to prevent ovarian strangulation and screening for Androgen Insensitivity Syndrome (AIS) remain controversial. This study assesses the incidence of ovarian strangulation and AIS, and its associated risk factors. METHODS: Electronic patient records were used to study girls aged 0-15 years who underwent inguinal hernia repair between 2000 and 2017. Patients with incomplete data were excluded. Risk factors were identified using logistic regression. RESULTS: This study includes 1084 girls (median (IQR) age: 133.5 (14-281) weeks) who underwent 1132 hernia repairs (1015 unilateral, 117 bilateral) within a median (IQR) time interval of 12 (6-23) days following diagnosis. Hernia sac intraoperatively contained ovary in 235 (21.7%) patients, ovary was strangulated in 14 (6%). Risk factors for ovarian strangulation were younger gestational age (OR 0.49), higher birthweight (OR 32.18), and first presentation at the emergency department (OR 13.07). However data were partly missing. Ectopic testis was found in seven (0.6%) patients. Metachronous contralateral inguinal hernia and ipsilateral recurrence developed in 6.1% and 0.3%, respectively. CONCLUSIONS: Ovarian hernia was diagnosed in 21.7%, and ovary was strangulated in 6%. No definite conclusions can be drawn regarding risk factors for strangulation and timing of surgery in girls with irreducible ovarian hernia. LEVEL OF EVIDENCE: Level III.

Botulinum toxin injections after surgery for Hirschsprung disease: Systematic review and meta-analysis.

BACKGROUND: A large proportion of patients with Hirschsprung disease experience persistent obstructive symptoms after corrective surgery. Persistent obstructive symptoms may result in faecal stasis that can develop into Hirschsprung-associated enterocolitis, a potential life-threatening condition. Important treatment to improve faecal passage is internal anal sphincter relaxation using botulinum toxin injections. AIM: To give an overview of all empirical evidence on the effectiveness of botulinum toxin injections in patients with Hirschsprung disease. METHODS: A systematic review and meta-analysis was done by searching PubMed, EMBASE and the Cochrane Library, using entry terms related to: (1) Hirschsprung disease; and (2) Botulinum toxin injections. 14 studies representing 278 patients met eligibility criteria. Data that were extracted were proportion of patients with improvement of obstructive symptoms or less enterocolitis after injection, proportion of patients with adverse effects and data on type botulinum toxin, mean dose, average age at first injection and patients with associated syndromes. Random-effects meta-analysis was used to aggregate effects and random-effects meta-regression was used to test for possible confounding factors. RESULTS: Botulinum toxin injections are effective in treating obstructive symptoms in on average 66% of patients [event rate (ER) = 0.66, P = 0.004, I 2 = 49.5, n = 278 patients]. Type of botulinum toxin, average dose, average age at first injections and proportion of patients with associated syndromes were not predictive for this effect. Mean 7 duration of improvement after one botulinum toxin injections was 6.4 mo and patients needed on average 2.6 procedures. There was a significant higher response rate within one month after botulinum toxin injections compared to more than one month after Botulinum toxin injections (ER = 0.79, vs ER = 0.46, Q = 19.37, P < 0.001). Botulinum toxin injections were not effective in treating enterocolitis (ER 0.58, P = 0.65, I 2 = 71.0, n = 52 patients). There were adverse effects in on average 17% of patients (ER = 0.17, P < 0.001, I 2 = 52.1, n = 187 patients), varying from temporary incontinence to mild anal pain. CONCLUSION: Findings from this systematic review and meta-analysis indicate that botulinum toxin injections are effective in treating obstructive symptoms and that adverse effects were present, but mild and temporary.

Pediatric thyroglossal duct cysts: Post-operative complications.

INTRODUCTION: Thyroglossal duct cysts (TGDCs) result from incomplete involution of the thyroglossal duct and are resected with a Sistrunk-procedure. We studied and graded severity of postoperative complications in children who underwent this procedure, with corresponding risk factors. METHODS: In our electronic health record system we reviewed the medical records of all patients aged <18 years, with surgically treated TGDC between 01-01-2005 and 31-12-2015 in two university hospitals. Risk factors (age, gender, recurrence at presentation, treatment hospital, cyst inflammation, cyst rupture, drain placement, antibiotics or postoperative infection) were studied by univariate analysis. The Clavien-Dindo surgical complication classification was used as postoperative surgical grading system. RESULTS: Of the ninety-one patients, with a mean age of 4.4 years, seven were referred from other hospitals with a recurrent TGDC. 24 patients (26.4%) had a complication. Hemorrhage and resection of thyroid cartilage were the most severe complications. Recurrence and wound infection (both n = 7, 7.7%) were most common. We could not identify risk factors for these complications. CONCLUSIONS: The treatment of children with thyroglossal duct cysts shows a considerable amount of complications. Pre-selected risk factors did not show any significant correlation with these complications.

Histopathology of human small intestinal and colonic ischemia-reperfusion: Experiences from human IR-models.

Intestinal ischemia-reperfusion (IR) injury is a frequent, but potentially life-threatening condition. Although much has been learned about its pathophysiology from animal IR models, the translation to the human setting is imperative for better understanding of its etiology. This could provide us with new insight into development of early detection and potential new therapeutic strategies. Over the past decade, we have studied the pathophysiology of human small intestinal and colonic ischemia-reperfusion (IR) in newly developed human in vivo IR models. In this review, we give an overview of new insights on the sequelae of human intestinal IR, with particular attention for the differences in histopathology between small intestinal and colonic IR.

Human small intestine is capable of restoring barrier function after short ischemic periods.

AIM: To assess intestinal barrier function during human intestinal ischemia and reperfusion (IR). METHODS: In a human experimental model, 6 cm of jejunum was selectively exposed to 30 min of ischemia (I) followed by 30 and 120 min of reperfusion (R). A sham procedure was also performed. Blood and tissue was sampled at all-time points. Functional barrier function was assessed using dual-sugar absorption tests with lactulose (L) and rhamnose (R). Plasma concentrations of citrulline, an amino acid described as marker for enterocyte function were measured as marker of metabolic enterocytes restoration. Damage to the epithelial lining was assessed by immunohistochemistry for tight junctions (TJs), by plasma marker for enterocytes damage (I-FABP) and analyzed by electron microscopy (EM) using lanthanum nitrate as an electrondense marker. RESULTS: Plasma L/R ratio's were significantly increased after 30 min of ischemia (30I) followed by 30 min of reperfusion (30R) compared to control (0.75 ± 0.10 vs 0.20 ± 0.09, P < 0.05). At 120 min of reperfusion (120R), ratio's normalized (0.17 ± 0.06) and were not significantly different from control. Plasma levels of I-FABP correlated with plasma L/R ratios measured at the same time points (correlation: 0.467, P < 0.01). TJs staining shows distortion of staining at 30I. An intact lining of TJs was again observed at 30I120R. Electron microscopy analysis revealed disrupted TJs after 30I with paracellular leakage of lanthanum nitrate, which restored after 30I120R. Furthermore, citrulline concentrations closely paralleled the histological perturbations during intestinal IR. CONCLUSION: This study directly correlates histological data with intestinal permeability tests, revealing that the human gut has the ability of to withstand short episodes of ischemia, with morphological and functional recovery of the intestinal barrier within 120 min of reperfusion.

Predictive Factors for Anastomotic Leakage After Colorectal Surgery: Study Protocol for a Prospective Observational Study (REVEAL Study).

BACKGROUND: Anastomotic leakage (AL) remains the most important complication following colorectal surgery, and is associated with high morbidity and mortality rates. Previous research has focused on identifying risk factors and potential biomarkers for AL, but the sensitivity of these tests remains poor. OBJECTIVE: This prospective multicenter observational study aims at combining multiple parameters to establish a diagnostic algorithm for colorectal AL. METHODS: This study aims to include 588 patients undergoing surgery for colorectal carcinoma. Patients will be eligible for inclusion when surgery includes the construction of a colorectal anastomosis. Patient characteristics will be collected upon consented inclusion, and buccal swabs, breath, stool, and blood samples will be obtained prior to surgery. These samples will allow for the collection of information regarding patients' inflammatory status, genetic predisposition, and intestinal microbiota. Additionally, breath and blood samples will be taken postoperatively and patients will be strictly observed during their in-hospital stay, and the period shortly thereafter. RESULTS: This study has been open for inclusion since August 2015. CONCLUSIONS: An estimated 8-10% of patients will develop AL following surgery, and they will be compared to non-leakage patients. The objectives of this study are twofold. The primary aim is to establish and validate a diagnostic algorithm for the pre-operative prediction of the risk of AL development using a combination of inflammatory, immune-related, and genetic parameters. Previously established risk factors and novel parameters will be incorporated into this algorithm, which will aid in the recognition of patients who are at risk for AL. Based on these results, recommendations can be made regarding the construction of an anastomosis or deviating stoma, and possible preventive strategies. Furthermore, we aim to develop a new algorithm for the post-operative diagnosis of AL at an earlier stage, which will positively reflect on short-term survival rates. TRIAL REGISTRATION: Clinicaltrials.gov: NCT02347735; https://clinicaltrials.gov/ct2/show/NCT02347735 (archived by WebCite at http://www.webcitation.org/6hm6rxCsA).

Non-invasive assessment of barrier integrity and function of the human gut.

Over the past decades evidence has been accumulating that intestinal barrier integrity loss plays a key role in the development and perpetuation of a variety of disease states including inflammatory bowel disease and celiac disease, and is a key player in the onset of sepsis and multiple organ failure in situations of intestinal hypoperfusion, including trauma and major surgery. Insight into gut barrier integrity and function loss is important to improve our knowledge on disease etiology and pathophysiology and contributes to early detection and/or secondary prevention of disease. A variety of tests have been developed to assess intestinal epithelial cell damage, intestinal tight junction status and consequences of intestinal barrier integrity loss, i.e. increased intestinal permeability. This review discusses currently available methods for evaluating loss of human intestinal barrier integrity and function.