Human Fetal TNF-α-Cytokine-Producing CD4+ Effector Memory T Cells Promote Intestinal Development and Mediate Inflammation Early in Life.

Although the fetal immune system is considered tolerogenic, preterm infants can suffer from severe intestinal inflammation, including necrotizing enterocolitis (NEC). Here, we demonstrate that human fetal intestines predominantly contain tumor necrosis factor-α (TNF-α)+CD4+CD69+ T effector memory (Tem) cells. Single-cell RNA sequencing of fetal intestinal CD4+ T cells showed a T helper 1 phenotype and expression of genes mediating epithelial growth and cell cycling. Organoid co-cultures revealed a dose-dependent, TNF-α-mediated effect of fetal intestinal CD4+ T cells on intestinal stem cell (ISC) development, in which low T cell numbers supported epithelial development, whereas high numbers abrogated ISC proliferation. CD4+ Tem cell frequencies were higher in inflamed intestines from preterm infants with NEC than in healthy infant intestines and showed enhanced TNF signaling. These findings reveal a distinct population of TNF-α-producing CD4+ T cells that promote mucosal development in fetal intestines but can also mediate inflammation upon preterm birth.

Long-term oncological outcomes of follicular thyroid cancer in adolescents and young adults: A nationwide population-based study.

BACKGROUND: Follicular thyroid carcinoma (FTC) in adolescents and young adults (AYAs) is rare and data on long-term oncological outcomes are scarce. This study aimed to describe the long-term recurrence and survival rates of AYAs with FTC, and identify risk factors for recurrence. METHODS: This is a retrospective cohort study combining two national databases, including all patients aged 15-39 years, diagnosed with FTC in The Netherlands between 2000 and 2016. Age, sex, tumor size, focality, positive margins, angioinvasion, pT-stage, and pN-stage were included in a Cox proportional hazard model to identify risk factors for recurrence. RESULTS: We included 192 patients. Median age was 31.0 years (IQR 24.7-36.3) and the male to female ratio was 1:4.1. Most patients presented with a minimally invasive FTC (MI-FTC) (95%). Five patients presented with synchronous metastases (2.6%), including two with locoregional metastases (1%) and three with distant metastases (1.6%). During a median follow-up of 12.0 years, three patients developed a recurrence (1.6%), of which one patient developed a local recurrence (33%), and two patients a distant recurrence (67%). Five patients died during follow-up (2.6%). Cause of death was not captured. A Cox proportional hazard model could not be performed due to the low number of recurrences. CONCLUSIONS: FTC in AYAs is generally characterized as a low-risk tumor, as it exhibits a very low recurrence rate, a high overall survival, and it typically presents as MI-FTC without synchronous metastases. These findings underscore the favorable long-term oncological prognosis of FTC in AYAs.

Experimental evaluation of laparoscopic laser speckle contrast imaging to visualize perfusion deficits during intestinal surgery.

BACKGROUND: Ischemia at the site of an intestinal anastomosis is one of the most important risk factors for anastomotic leakage (AL). Consequently, adequate intestinal microperfusion is essential for optimal tissue oxygenation and anastomotic healing. As visual inspection of tissue viability does not guarantee an adequate objective evaluation of intestinal microperfusion, surgeons are in dire need of supportive tools to decrease anastomotic leakage after colorectal surgery. METHODS: In this feasibility study, laparoscopic laser speckle contrast imaging (LSCI) was used to evaluate intestinal microperfusion in an experimental ischemic bowel loop model. Both large and small ischemic loops were created from the small intestine of a pig; each loop was divided into 5 regions of interest (ROI) with varying levels of ischemia. Speckle contrast and local capillary lactate (LCL) was measured in all ROIs. RESULTS: Both real-time visualization of intestinal microperfusion and induced perfusion deficits was achieved in all bowel loops. As a result, the emergence of regions of intestinal ischemia could be predicted directly after iatrogenic perfusion limitation, whereas without LSCI signs of decreased intestinal viability could only be seen after 30 minutes. Additionally, a significant relation was found between LCL and LSCI. CONCLUSION: In conclusion, LSCI can achieve real-time intraoperative visualization of intestinal microperfusion deficits, allowing for accurate prediction of long-term postoperative ischemic complications. With this revealing capacity, LSCI could potentially facilitate surgical decision-making when constructing intestinal anastomoses in order to mitigate ischemia-related complications such as AL.

Prognostic accuracy of factors associated with poor outcome in prenatally diagnosed sacrococcygeal teratoma: A systematic review and meta-analysis.

Several factors associated with poor outcome in patients with prenatally diagnosed sacrococcygeal teratoma (SCT) have been found. However, the prognostic accuracy of these factors has not been well established. Therefore, we aimed to systematically review the prognostic accuracy of factors associated with poor outcome in these patients. We queried Search Premier, COCHRANE Library, EMCARE, EMBASE, PubMed, ScienceDirect, and Web of Science databases to identify studies regarding patients with prenatally diagnosed SCT. Poor outcome was defined as termination of pregnancy (TOP), intrauterine fetal death (IUFD), or perinatal death. We estimated the odds ratio of factors associated with poor outcome. Eleven studies (447 patients) were included. Overall mortality, including TOP, was 34.9%. Factors associated with poor outcome in fetuses with prenatally diagnosed SCT were cardiomegaly, hypervascular tumor, solid tumor morphology, fetal hydrops, and placentomegaly. A tumor volume to fetal weight ratio (TFR) of >0.12 before a gestational age of 24 weeks is predictive of poor outcome. The prognostic accuracy of factors associated with poor outcome in fetuses prenatally diagnosed with SCT seems promising. Factors associated with cardiac failure such as cardiomegaly, hypervascular tumor, solid tumor morphology, fetal hydrops, placentomegaly, and TFR >0.12 were found to be predictive of poor outcome.

Diagnostic accuracy of ultrasonography to distinguish thyroglossal duct cysts from dermoid cysts in children with a midline neck swelling.

INTRODUCTION: Midline neck swellings are very common in children and mostly caused by thyroglossal duct cysts (TGDCs) or dermoid cysts (DCs). Since DCs can undergo simple excision, whilst TGDCs demand more thorough resection via Sistrunk procedure, it is important to differentiate between both pre-operatively. Previous studies have suggested an ultrasound-score (SIST) based on presence of septae, wall irregularity and solid components could do so. This study aims to evaluate the diagnostic accuracy of this score. METHODS: All patients (≤18 years) undergoing surgery between 2006 and 2018 for a midline neck mass at our tertiary centre with a histopathological diagnosis of TGDC or DC were retrospectively included. The pre-operative ultrasound was evaluated by an experienced radiologist and the SIST as well as location, tract, echogenicity, margin and multilocularity were scored. RESULTS: We included 97 children, of whom 67 (69 %) with TGDCs. The SIST showed a sensitivity of 37 %, specificity of 97 %, a positive predictive value of 96 % and a negative predictive value of 35 % for the SIST-score in detecting TGDCs, which resulted in an AUC of 0.67. In addition, internal echogenicity (P < 0.01) and margin definition (P < 0.01) were significantly associated to TGDC diagnosis whilst location and multilocularity were deemed insignificant following Bonferroni correction. CONCLUSION: We conclude that the SIST-score seems very capable to rule in TGDC. However, the SIST-score is far from making a clear distinction between DC and TGDCs preoperatively. The addition of other ultrasound variables, such as margin definition and echogenicity, might increase the diagnostic accuracy and demands further research.

Cardiac anomalies in children with congenital duodenal obstruction: a systematic review with meta-analysis.

BACKGROUND: Cardiac anomalies occur frequently in patients with congenital duodenal obstruction (DO). However, the exact occurrence and the type of associated anomalies remain unknown. Therefore, the aim of this systematic review is to aggregate the available literatures on cardiac anomalies in patients with DO. METHODS: In July 2022, a search was performed in PubMed and Embase.com. Studies describing cardiac anomalies in patients with congenital DO were considered eligible. Primary outcome was the pooled percentage of cardiac anomalies in patients with DO. Secondary outcomes were the pooled percentages of the types of cardiac anomalies, type of DO, and trisomy 21. A meta-analysis was performed to pool the reported data. RESULTS: In total, 99 publications met our eligibility data, representing 6725 patients. The pooled percentage of cardiac anomalies was 29% (95% CI 0.26-0.32). The most common cardiac anomalies were persistent foramen ovale 35% (95% CI 0.20-0.54), ventricular septal defect 33% (95% CI 0.24-0.43), and atrial septal defect 33% (95% CI 0.26-0.41). The most prevalent type of obstruction was type 3 (complete atresias), with a pooled percentage of 54% (95% CI 0.48-0.60). The pooled percentage of Trisomy 21 in patients with DO was 28% (95% CI 0.26-0.31). CONCLUSION: This review shows cardiac anomalies are found in one-third of the patients with DO regardless of the presence of trisomy 21. Therefore, we recommend that patients with DO should receive preoperative cardiac screening. LEVEL OF EVIDENCE: II.

Did Age at Surgery Influence Outcome in Patients With Hirschsprung Disease? A Nationwide Cohort Study in the Netherlands.

OBJECTIVES: Hirschsprung disease (HD) requires surgical resection of affected bowel, but the current evidence is inconclusive regarding the optimal age for resection. The aim of this study was to assess whether age at resection of the aganglionic segment is a determinant for surgical outcomes. METHODS: A cross-sectional cohort study was done including all consecutive patients with HD between 1957 and 2015, aged 8 years or older (n = 830), who were treated in 1 of the 6 pediatric surgical centers in the Netherlands. Outcome measures were mortality, postoperative complications, stoma rate and redo surgery rate, retrieved from the medical records. Additionally, constipation and fecal incontinence rate in long term were assessed with the Defecation and Continence Questionnaire (DeFeC and P-DeFeC). RESULTS: The medical records of 830 patients were reviewed, and 346 of the 619 eligible patients responded to the follow-up questionnaires (56%). There was a small increase in the risk of a permanent stoma [odds ratio (OR) 1.01 (95% confidence interval {CI}: 1.00-1.02); P = 0.019] and a temporary stoma [OR 1.01 (95% CI: 1.00-1.01); P = 0.022] with increasing age at surgery, regardless of the length of the aganglionic segment and operation technique. Both adjusted and unadjusted for operation technique, length of disease, and temporary stoma, age at surgery was not associated with the probability and the severity of constipation and fecal incontinence in long term. CONCLUSIONS: In this study, we found no evidence that the age at surgery influences surgical outcomes, thus no optimal timing for surgery for HD could be determined.

Predictive factors for surgical treatment in preterm neonates with necrotizing enterocolitis: a multicenter case-control study.

Necrotizing enterocolitis (NEC) is one of the most common and lethal gastrointestinal diseases in preterm infants. Early recognition of infants in need for surgical intervention might enable early intervention. In this multicenter case-control study, performed in nine neonatal intensive care units, preterm born infants (< 30 weeks of gestation) diagnosed with NEC (stage ≥ IIA) between October 2014 and August 2017 were divided into two groups: (1) medical (conservative treatment) and (2) surgical NEC (sNEC). Perinatal, clinical, and laboratory parameters were collected daily up to clinical onset of NEC. Univariate and multivariate logistic regression analyses were applied to identify potential predictors for sNEC. In total, 73 preterm infants with NEC (41 surgical and 32 medical NEC) were included. A low gestational age (p value, adjusted odds ratio [95%CI]; 0.001, 0.91 [0.86-0.96]), no maternal corticosteroid administration (0.025, 0.19 [0.04-0.82]), early onset of NEC (0.003, 0.85 [0.77-0.95]), low serum bicarbonate (0.009, 0.85 [0.76-0.96]), and a hemodynamically significant patent ductus arteriosus for which ibuprofen was administered (0.003, 7.60 [2.03-28.47]) were identified as independent risk factors for sNEC.Conclusions: Our findings may support the clinician to identify infants with increased risk for sNEC, which may facilitate early decisive management and consequently could result in improved prognosis. What is Known: • In 27-52% of the infants with NEC, a surgical intervention is indicated during its disease course. • Absolute indication for surgical intervention is bowel perforation, whereas fixed bowel loop or clinical deterioration highly suggestive of bowel perforation or necrosi, is a relative indication. What is New: • Lower gestational age, early clinical onset, and no maternal corticosteroids administration are predictors for surgical NEC. • Low serum bicarbonate in the 3 days prior clinical onset and patent ductus arteriosus for which ibuprofen was administered predict surgical NEC.

Factors associated with poor outcome in fetuses prenatally diagnosed with sacrococcygeal teratoma.

AIM OF THE STUDY: Outcome of fetuses, prenatally diagnosed with sacrococcygeal teratoma (SCT), is still poorly documented. This study assesses the incidence and prenatal predictors of outcome in all fetuses prenatally diagnosed with SCT. METHODS: This is a retrospective study on all fetuses prenatally diagnosed with SCT from 1998 to 2018 in the Netherlands. Poor outcome was defined as terminations of pregnancy (TOP) because of expected unfavorable outcome, intrauterine fetal death, or early neonatal death. Potential risk factors for poor outcome were analyzed. MAIN RESULTS: Eighty-four fetuses were included. Sixteen (19.0%) TOPs were excluded from statistical analysis. Eleven of the remaining 68 fetuses had poor outcome. Overall mortality was 32.1%, with a mortality excluding TOPs of 13.1%. Thirteen fetal interventions were performed in 11 (13.1%) fetuses. Potential risk factors for poor outcome were the presence of fetal hydrops (OR: 21.0, CI: 2.6-275.1, p = 0.012) and cardiomegaly (OR: 10.3, CI: 1.9-55.8, p = 0.011). CONCLUSIONS: The overall mortality of fetuses prenatally diagnosed with SCTs including tTOP was 32.1%. This high mortality rate was mainly due to termination of pregnancy. Mortality excluding TOP was 13.1%. Potential risk factors for poor outcome were fetal hydrops and cardiomegaly.

Females Are More Resistant to Ischemia-Reperfusion-induced Intestinal Injury Than Males: A Human Study.

BACKGROUND AND OBJECTIVE: Sex differences in responses to intestinal ischemia-reperfusion (IR) have been recognized in animal studies. We aimed to investigate sexual dimorphism in human small intestinal mucosal responses to IR. METHODS: In 16 patients (8 men and 8 women) undergoing pancreaticoduodenectomy, an isolated part of jejunum was subjected to IR. In each patient, intestinal tissue and blood was collected directly after 45 minutes of ischemia without reperfusion (45I-0R), after 30 minutes of reperfusion (45I-30R), and after 120 minutes of reperfusion (45I-120R), as well as a control sample not exposed to IR, to assess epithelial damage, unfolded protein response (UPR) activation, and inflammation. RESULTS: More extensive intestinal epithelial damage was observed in males compared to females. Intestinal fatty acid binding protein (I-FABP) arteriovenous (V-A) concentrations differences were significantly higher in males compared to females at 45I-0R (159.0 [41.0-570.5] ng/mL vs 46.9 [0.3-149.9] ng/mL). Male intestine showed significantly higher levels of UPR activation than female intestine, as well as higher number of apoptotic Paneth cells per crypt at 45I-30R (16.4% [7.1-32.1] vs 10.6% [0.0-25.4]). The inflammatory response in male intestine was significantly higher compared to females, with a higher influx of neutrophils per villus at 45I-30R (4.9 [3.1-12.0] vs 3.3 [0.2-4.5]) and a higher gene expression of TNF-α and IL-10 at 45I-120R. CONCLUSION: The human female small intestine seems less susceptible to IR-induced tissue injury than the male small intestine. Recognition of such differences could lead to the development of novel therapeutic strategies to reduce IR-associated morbidity and mortality.

Management of appendiceal mass and abscess in children; early appendectomy or initial non-operative treatment? A systematic review and meta-analysis.

BACKGROUND: Appendiceal mass and abscess and its treatment are associated with significant morbidity and high costs. Still, the optimal treatment strategy is the point of debate. Therefore, this systematic review and meta-analysis aimed to compare overall complications between initial non-operative treatment (NOT) and early appendectomy (EA) in children with appendiceal mass and/or abscess. METHODS: Pubmed and Embase were searched. Only randomized controlled trials and prospective or historical cohort studies that compared NOT with EA in children with appendiceal mass or abscess in terms of complications were eligible for inclusion. Risk of bias was assessed. Primary outcome was the overall complication rate. Secondary, length of stay and readmission rate were investigated. A meta-analysis of overall complications associated with both treatment strategies was performed. RESULTS: 14 of 7083 screened studies were selected, including 1022 children in the NOT group and 333 in the EA group. Duration of follow-up ranged between four weeks and 12 years. Risk of bias was moderate in four and serious in 10 studies. NOT was associated with a lower overall complication rate (risk ratio (RR) 0.37 [95% confidence interval (CI) 0.21-0.65]). However, NOT led to increased length of stay (mean difference varied between 0.2 and 8.4 days) and higher readmission rate (RR 1.75 [95%CI 0.79-3.89]), although not significantly. Interval appendectomy after NOT was performed as a routine procedure in all but one study. This study found a recurrence rate of 34% in a group of 38 patients during a follow-up period of 3.4 ± 1.7 years. CONCLUSION: NOT may reduce the overall complication rate compared to EA, but the evidence is very uncertain. As evidence is scarce, and of low level, and heterogeneity between studies is substantial, the results should be interpreted with caution. Large prospective studies are needed to determine the optimal treatment strategy for children with appendiceal mass and/or abscess.

Perioperative apnea in infants with hypertrophic pyloric stenosis: A systematic review.

BACKGROUND: Infantile hypertrophic pyloric stenosis (IHPS) leads to excessive vomiting and metabolic alkalosis, which may subsequently cause apnea. Although it is generally assumed that metabolic derangements should be corrected prior to surgery to prevent apnea, the exact incidence of perioperative apneas in infants with IHPS and the association with metabolic alkalosis are unknown. We performed this systematic review to assess the incidence of apnea in infants with IHPS and to verify the possible association between apnea and metabolic alkalosis. METHODS: We searched MEDLINE, Embase, and Cochrane library to identify studies regarding infants with metabolic alkalosis, respiratory problems, and hypertrophic pyloric stenosis. We conducted a descriptive synthesis of the findings of the included studies. RESULTS: Thirteen studies were included for analysis. Six studies described preoperative apnea, three studies described postoperative apnea, and four studies described both. All studies were of low quality or had other research questions. We found an incidence of 27% of preoperative and 0.2%-16% of postoperative apnea, respectively. None of the studies examined the association between apnea and metabolic alkalosis in infants with IHPS. CONCLUSIONS: Infants with IHPS may have a risk to develop perioperative apnea. However, the incidence rates should be interpreted with caution because of the low quality and quantity of the studies. Therefore, further studies are required to determine the incidence of perioperative apnea in infants with IHPS. The precise underlying mechanism of apnea in these infants is still unknown, and the role of metabolic alkalosis should be further evaluated.

Redo surgery with longitudinal resection for dilated bowel in Hirschsprung disease: an illustrative case series.

PURPOSE: Patients with Hirschsprung disease (HD) can have persistent obstructive symptoms after resection of the aganglionic segment. If obstructive symptoms are treated inadequately, this may lead to recurrent faecal stasis and impaction, and may result in severe distension of the bowel. A permanently distended bowel which not responds to conservative treatment may be an indication for redo surgery. The aim of this study is to describe our experiences and the short-term results of a novel technique: longitudinal antimesenteric resection with a longitudinal anastomosis. METHODS: We reviewed the medical records of our three patients who underwent longitudinal resection of severe distended bowel. This technique aims to improve defecation by improving faecal passage and is characterized by resection of the antimesenteric side of the distended intestinal segment, followed by plication with a longitudinal anastomosis. In this paper, this novel technique is described in detail, as well as short-term outcomes. RESULTS: All patients had an uneventful recovery after longitudinal antimesenteric resection. During follow-up, the functional outcomes were excellent, with a large improvement of bowel function. All patients were continent for faeces, and treated with low-dose laxatives or occasional preventive irrigation in one patient. There were no more complaints of persistent constipation or soiling. CONCLUSION: Longitudinal resection is a surgical redo-procedure offering large benefits for patients with Hirschsprung disease with distended bowel after primary surgery.

SM22 a Plasma Biomarker for Human Transmural Intestinal Ischemia.

OBJECTIVE: To evaluate the diagnostic potential of smooth muscle protein of 22 kDa (SM22) as plasma biomarker for the detection of transmural intestinal ischemia. BACKGROUND: Acute mesenteric ischemia is an abdominal emergency requiring rapid diagnosis and treatment. Especially, detection of transmural damage is imperative because it mandates emergency surgery. Since early clinical and radiological signs are nonspecific, there is an urgent need for accurate biomarkers. SM22 is a potential marker for transmural damage because of its abundant expression in intestinal smooth muscles. METHODS: SM22 concentrations were measured using a newly built enzyme-linked immunosorbent assay. SM22 release was assessed in plasma and intestinal tissue of rats subjected to intestinal ischemia. Blood and tissue were sampled at baseline and followed up to 24 hours of ischemia. Next, organ-specific SM22 arteriovenous concentration differences were studied in both rats and patients. Finally, plasma from patients with intestinal ischemia, other acute abdominal complaints, and healthy volunteers were tested for SM22. RESULTS: SM22 concentrations were significantly elevated in rats from 4 hours of ischemia onwards. Furthermore, SM22 plasma concentrations closely paralleled the histological increasing degree of intestinal smooth muscle damage. Arteriovenous calculations showed that SM22 was specifically released by the intestines and renally cleared. First data of SM22 release in man demonstrated that patients with transmural intestinal ischemia had significantly higher plasma SM22 levels than patients with only ischemic mucosal injury, other acute abdominal diseases, or healthy controls. CONCLUSIONS: This study shows that SM22 is released into the circulation upon severe ischemia of the intestinal muscle layers. Plasma levels of SM22 are potentially useful for the detection of transmural intestinal damage.

Cyclooxygenase-2 Is Essential for Colorectal Anastomotic Healing.

OBJECTIVE: To study the effects of COX-2 on colonic surgical wound healing. BACKGROUND: Cyclooxygenase-2 (COX-2) is a key enzyme in gastrointestinal homeostasis. COX-2 inhibitors have been associated with colonic anastomotic leakage. METHODS: Wildtype, COX-2 knockout and COX-2 heterozygous mice were subjected to a model of colonic anastomotic leakage, and were treated with vehicle, diclofenac, or prostaglandin E2 (PGE2), the most important COX-2 product in the intestine. We assessed anastomotic leakage, mortality, angiogenesis, and inflammation. Furthermore, we investigated the association between anastomotic leakage and a human polymorphism of the COX-2 gene resulting in low COX-2 levels. RESULTS: Diclofenac, a nonsteroidal anti-inflammatory drug inhibiting COX-2, increased anastomotic leakage compared to vehicle-treated mice (100% vs 25%, respectively). Similarly, 92% of COX-2-deficient mice developed anastomotic leakage (P = 0.003) compared to WT. PGE2 partly rescued this severe phenotype because only 46% of PGE2-administered COX-2 knockout mice developed anastomotic leakage (P = 0.02). This may be related to decreased neovascularization, because decreased CD31 staining, indicating less blood vessels, was observed in COX-2 mice (2 vessels/mm vs 6 vessels/mm in controls (P = 0.03)). This effect could partly be reversed by administration of PGE2 to COX-2 mice. No significant differences in inflammation were found. PTGS2-765G>C polymorphism in humans, associated with reduced COX-2 expression, was associated with higher anastomotic leakage rates. CONCLUSIONS: COX-2-induced PGE2 production is essential for intestinal wound healing after colonic surgery, possibly via its effects on angiogenesis. These data emphasize that COX-2 inhibitors should be avoided after colonic surgery, and administration of PGE2 might be favorable for a selection of patients.

Patient-Reported Defecation and Micturition Problems Among Adults Treated for Sacrococcygeal Teratoma During Childhood--The Need for New Surveillance Strategies.

BACKGROUND: To evaluate defecation and micturition complaints in adults treated for sacrococcygeal teratoma (SCT) during childhood and to identify risk factors for soiling, urinary incontinence, and constipation beyond childhood. PROCEDURE: Records of patients aged ≥18 treated for SCT during infancy in the Netherlands were retrospectively reviewed. Frequency and severity of soiling, constipation, and urinary incontinence were evaluated using questionnaires designed in line with the Krickenbeck classification. Problems during childhood were compared to outcomes at adult age in part of the cohort. Associations between patient- and disease-related factors with complaints beyond childhood were analyzed with the chi-square test or Fisher's exact test, when appropriate. RESULTS: Of 47 included patients (mean age 26.2 years, SD ±6.5), 49% reported at least one defecation or micturition complaint. Urinary incontinence was present in 30% and had a greater negative impact than soiling (24%). Ten patients (21%) reported constipation; five found this severely bothering. Three patients reported social restrictions due to defecation or micturition complaints (6.4%). While sex and tumor histology were not identified as risk factors, a tumor diameter of >10 cm and Altman type I or type II SCT were associated with constipation during adulthood. CONCLUSIONS: One-third of the patients treated for SCT during childhood reported urinary and defecation problems beyond childhood. In only a minority of cases, these led to social restrictions. A greater tumor diameter was associated with a higher risk of constipation during adulthood. Prolonged surveillance strategies are advised for all patients with SCT.

International consensus statement regarding the use of animal models for research on anastomoses in the lower gastrointestinal tract.

PURPOSE: This project aimed to reach consensus on the most appropriate animal models and outcome measures in research on anastomoses in the lower gastrointestinal tract (GIT). The physiology of anastomotic healing remains an important research topic in gastrointestinal surgery. Recent results from experimental studies are limited with regard to comparability and clinical translation. METHODS: PubMed and EMBASE were searched for experimental studies investigating anastomotic healing in the lower GIT published between January 1, 2000 and December 31, 2014 to assess currently used models. All corresponding authors were invited for a Delphi-based analysis that consisted of two online survey rounds followed by a final online recommendation survey to reach consensus on the discussed topics. RESULTS: Two hundred seventy-seven original articles were retrieved and 167 articles were included in the systematic review. Mice, rats, rabbits, pigs, and dogs are currently being used as animal models, with a large variety in surgical techniques and outcome measures. Forty-four corresponding authors participated in the Delphi analysis. In the first two rounds, 39/44 and 35/39 participants completed the survey. In the final meeting, 35 experts reached consensus on 76/122 items in six categories. Mouse, rat, and pig are considered appropriate animal models; rabbit and dog should be abandoned in research regarding bowel anastomoses. ARRIVE guidelines should be followed more strictly. CONCLUSIONS: Consensus was reached on several recommendations for the use of animal models and outcome measurements in research on anastomoses of the lower GIT. Future research should take these suggestions into account to facilitate comparison and clinical translation of results.

Evaluation of chemotherapeutic sequelae and quality of life in survivors of malignant sacrococcygeal teratoma.

PURPOSE: The impact of chemotherapeutic sequelae on long-term quality of life (QoL) for survivors of malignant sacrococcygeal teratoma (SCT) is unknown. The incidence of chemotherapeutic toxicity in patients treated for malignant SCT and possible effects on the QoL were analyzed. METHODS: Retrospective chart review of patients ≥18 years treated for SCT in the Netherlands was performed. Present QoL was evaluated using the SF-36 questionnaire. The results of survivors of malignant SCT were compared to those of patients treated for benign SCT. RESULTS: Fifty-one of 76 traceable patients consented to participate. The results of 47 (92.2 %), 9 men and 38 women (median age 25.4 years, range 18.3-41.2), were analyzed. Eleven had been treated for malignancy; 63.6 % suffered from at least one chemotherapeutic sequel with hearing loss as the most common one. Results for both groups were similar on all but one SF-36 subcategory; those treated for malignant tumor scored significantly lower on the subcategory physical functioning (p = 0.02). CONCLUSION: Despite the high incidence of chemotherapeutic sequelae among survivors of malignant SCT, their QoL does not differ from that of those treated for benign SCT. Even though their physical functioning is restricted, daily activities and psychosocial functioning of survivors of malignant SCT are not restricted.

Functional compromise reflected by sarcopenia, frailty, and nutritional depletion predicts adverse postoperative outcome after colorectal cancer surgery.

OBJECTIVE: To determine the association of sarcopenia with postoperative morbidity and mortality after colorectal surgery. BACKGROUND: Functional compromise in elderly colorectal surgical patients is considered as a significant factor of impaired postoperative recovery. Therefore, the predictive value of preoperative functional compromise assessment was investigated. Sarcopenia is a hallmark of functional compromise. METHODS: A total of 310 consecutive patients who underwent oncologic colorectal surgery were included in a prospective digital database. Sarcopenia was assessed using the L3 muscle index utilizing Osirix on preoperative computed tomography. Groningen Frailty Indicator and Short Nutritional Assessment Questionnaire scores were used to assess frailty and nutritional compromise. Predictors for anastomotic leakage, sepsis, and mortality were analyzed by logistic regression analysis. RESULTS: Age was an independent predictor of mortality [P = 0.04; odds ratio, 1.17; 95% confidence interval (CI), 1.01-1.37]. Thirty-day/in-hospital mortality rate in sarcopenic patients was 8.8% versus 0.7% in nonsarcopenic patients (P = 0.001; odds ratio, 15.5; 95% CI, 2.00-120). Sarcopenia was not predictive for anastomotic leakage or sepsis. Combination of high Short Nutritional Assessment Questionnaire score, high Groningen Frailty Indicator score, and sarcopenia strongly predicted sepsis (P = 0.001; odds ratio, 25.1; 95% CI, 5.11-123), sensitivity, 46%; specificity, 97%; positive likelihood ratio, 13 (95% CI, 4.4-38); negative likelihood ratio, 0.57 (95% CI, 0.33-0.97). CONCLUSIONS: Functional compromise in colorectal cancer surgery is associated with adverse postoperative outcome. Assessment of functional compromise by means of a nutritional questionnaire (Short Nutritional Assessment Questionnaire), a frailty questionnaire (Groningen Frailty Indicator), and sarcopenia measurement (L3 muscle index) can accurately predict postoperative sepsis.

Loss of Skeletal Muscle Mass During Neoadjuvant Chemoradiotherapy Predicts Postoperative Mortality in Esophageal Cancer Surgery.

BACKGROUND: Esophageal surgery is associated with complications and mortality. It is highly important to develop tools predicting unfavorable postoperative outcome. Esophageal cancer and neoadjuvant chemoradiotherapy (CRT) induce skeletal muscle wasting, which leads to diminished physiologic reserves. The purpose of this study was to investigate whether the degree of muscle mass lost during neoadjuvant CRT predicts postoperative mortality. METHODS: A total of 123 consecutive patients undergoing surgery for esophageal malignancy in the period 2008-2012 were included, of whom 114 received neoadjuvant CRT. Skeletal muscle mass was measured on routinely performed CT scans by assessing L3 muscle index (according to the Prado method) before and after neoadjuvant CRT, and the amount of muscle mass lost during neoadjuvant CRT (muscle loss index) was calculated. It was investigated whether this amount was associated with postoperative 30-day or in-hospital mortality and morbidity. RESULTS: In the complete cohort, no significant association between loss of muscle mass and mortality was found. However, skeletal muscle mass was significantly lower in patients with stage III-IV tumors compared with stage I-II tumors, prior to neoadjuvant CRT. In the stage III-IV subgroup, the amount of muscle mass lost during neoadjuvant CRT was predictive of postoperative mortality: -13.5 % (standard deviation 6.2 %) in patients who died postoperatively compared with -5.0 % (standard deviation 8.3 %) in surviving patients, p = 0.02. CONCLUSIONS: Measurement of muscle mass loss during neoadjuvant chemoradiotherapy may provide a readily available and inexpensive assessment to identify patients at risk for developing unfavorable postoperative outcome after resection of esophageal malignancies, especially in patients with stage III-IV tumors.