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INTRODUCTION: Predicted 1-year survival of children with trisomy 18 (T18) has increased to 59.3%. We aimed to systematically review the characteristics, management, and outcomes of children with T18 and hepatoblastoma. METHODS: A systematic literature review of the PubMed, Embase, Scopus, Web of Science, and Cochrane Library databases was performed according to the PRISMA 2020 statement (end-of-search date: 03/03/2024). RESULTS: Fifty studies reporting on 70 patients were included. The median age at diagnosis was 11.5 months, 85.9% were female (n = 55/64), and 15.0% had mosaic T18 (n = 6/40). Diagnosis was made during symptom evaluation (most commonly hepatomegaly or abdominal mass) in 45.5% (n = 15/33), incidentally in 24.2% (n = 8/33), during surveillance with abdominal ultrasound in 18.2% (n = 6/33), and at autopsy in 12.1% (n = 4/33). The median tumor size was 6.4 cm, 33.3% had multiple tumors (n = 14/42), and metastasis was present in one patient (3.8%; n = 1/26). Neoadjuvant chemotherapy was administered in 42.6% (n = 26/61) and adjuvant chemotherapy in 31.6% (n = 18/57). Surgical treatment was performed in 64.2% (n = 43/67). Of the patients not diagnosed on autopsy, overall mortality was 35.5% (n = 22/62) over a median follow-up of 11.0 months. Among the 26 deceased patients (including those diagnosed on autopsy), the most common causes of death were cardiopulmonary disease (38.5%, n = 10/26) and tumor progression (30.8%, n = 8/26). CONCLUSIONS: T18 does not preclude resection with curative intent for hepatoblastoma. Combination of surgery and chemotherapy should be considered in children on an individualized basis depending on tumor characteristics and underlying cardiopulmonary comorbidities. Locoregional modalities may have a role in the setting of severe comorbidities. LEVEL OF EVIDENCE: Level IV evidence.
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OBJECTIVE: To evaluate for disparities in surgical care among US children with hepatoblastoma (HB) and hepatocellular carcinoma (HCC). STUDY DESIGN: In this retrospective National Cancer Database study (2004-2015), children aged <18 years with HB or HCC were included. Multivariable mixed-effects logistic regression was used to evaluate the association of sociodemographic factors (age, sex, race and ethnicity, insurance status, income, proximity to treating hospital) with the odds of undergoing surgical treatment after adjusting for disease-related factors (tumor size, metastasis, comorbidities) and hospital-level effects. Subgroup analyses by tumor histology were performed. RESULTS: A total of 811 children were included (HB: 80.9%; HCC: 19.1%), of which 610 (75.2%) underwent surgical treatment. Following adjustment, decreased odds of undergoing surgical treatment were associated with Black race (OR: 0.46 vs White, 95% CI [95% CI]: 0.26-0.80, P = .01), and having Medicaid (OR: 0.58 vs private, 95% CI: 0.38-0.88, P = .01) or no insurance (OR: 0.33 vs private, 95% CI: 0.13-0.80, P = .02). In children with HB, Black race was associated with decreased odds of undergoing surgical treatment (OR: 0.47 vs White, 95% CI: 0.25-0.89, P = .02). In children with HCC, Medicaid (OR: 0.10 vs private, 95% CI: 0.03-0.35, P < .001), or no insurance status (OR: 0.10 vs private, 95% CI: 0.01-0.83, P = .03) were associated with decreased odds of undergoing surgical treatment. Other than metastatic disease, no additional factors were associated with likelihood of surgical treatment in any group. CONCLUSIONS: Black race and having Medicaid or no insurance are independently associated with decreased odds of surgical treatment in children with HB and HCC, respectively. These children may be less likely to undergo curative surgery for their liver cancer.
Subject(s)
Carcinoma, Hepatocellular , Healthcare Disparities , Hepatoblastoma , Liver Neoplasms , Humans , Hepatoblastoma/surgery , Carcinoma, Hepatocellular/surgery , Liver Neoplasms/surgery , Liver Neoplasms/pathology , Male , Female , Child , Retrospective Studies , Child, Preschool , Infant , United States , Healthcare Disparities/statistics & numerical data , Healthcare Disparities/ethnology , Adolescent , Sociodemographic Factors , Medicaid/statistics & numerical data , Socioeconomic Factors , Databases, FactualABSTRACT
INTRODUCTION: Gastrostomy tube (GT) placement is common in infants following repair of congenital heart defects. We aimed to determine rate of operative complications and predictors of short-term GT use to counsel parents regarding the risks and benefits of GT placement. METHODS: We reviewed infants aged <1 y with congenital heart disease who underwent GT placement after cardiac surgery between 2018 and 2021. Demographics and clinical data were collected and analyzed. Comparisons were made between infants who required the GT for more than 1 y and those who required the GT for less than 1 y. RESULTS: One hundred thirty three infants were included; 35 (26%) suffered one or more complication including wound infection (4, 3%), granulation tissue (3, 2%), tube dislodgement (10), leakage from the tube (9), unplanned emergency department visit (15), and unplanned readmission (1). Thirty-four infants used the GT for feeds for 1 y or less (26%) including 17 (13%) who used it for 3 mo or less. Fifty-six infants had their GT removed during the study period (42%), 20 of whom required gastrocutaneous fistula closure (36%). Thirty-three infants had a GT placed on or before day of life 30, 17 (52%) used the GT for less than 1 y, and 10 (31%) used it for 3 mo or less. CONCLUSIONS: GT placement is associated with a relatively high complication and reoperation rate. GT placement in infants aged less than 30 d is associated with shorter duration of use. Risks, benefits, and alternatives such as nasogastric tube feeds should be discussed in the shared decision-making process for selected infants.
Subject(s)
Cardiac Surgical Procedures , Gastric Fistula , Infant , Humans , Gastrostomy/adverse effects , Gastric Fistula/etiology , Cardiac Surgical Procedures/adverse effects , Patient Readmission , Intubation, Gastrointestinal/adverse effects , Retrospective StudiesABSTRACT
INTRODUCTION: Children may require durable central venous catheters (CVCs) for various reasons. CVC-related integrity complications are common and can often be repaired at the bedside to increase lifetime. Variability in repair techniques can lead to complications, including the need for repeat repair and Central Line Associated Blood Stream Infection (CLABSI). METHODS: The impact of an educational curriculum to standardize tunneled CVC repairs for trainees on a pediatric surgery service was studied, focusing on comfort level with tunneled CVC repair and to determine the impact on complication rates. Rotating trainees studied a dedicated audiovisual educational curriculum comprised of a video, educational slides, and a practical component from November 2020 through January 2022. Experience and comfort level with tunneled CVC repairs were assessed before and after the rotation. CVCs repaired during the duration of the study were evaluated and compared to the period prior. RESULTS: Forty-nine individuals completed the pre- and post-training survey. Respondents (34.7%, n = 17) most commonly reported one year of surgical experience, and (79.6%, n = 39) had never observed or assisted in a repair previously. Following training, respondents felt more comfortable with all aspects of the CVC repair process (p < 0.001). There were no statistically significant differences in re-repair rates or CLABSI rates following the implementation of the curriculum. CONCLUSIONS: Tunneled CVC procedural repair variability can be standardized with a dedicated educational curriculum for rotating trainees, which improves knowledge and comfort with such procedures.
Subject(s)
Catheter-Related Infections , Catheterization, Central Venous , Central Venous Catheters , Child , Humans , Central Venous Catheters/adverse effects , Catheter-Related Infections/prevention & control , Retrospective Studies , Catheterization, Central Venous/adverse effects , CurriculumABSTRACT
As the transgender population in the United States grows, gender-affirming care is becoming increasingly relevant to the practice of pediatric surgery. Medical care for the transgender and gender diverse population is a politically charged topic with significant complexity and opportunities for clarification. It is important for providers to better understand this population's unique health and social needs. This review aims to debunk long-standing myths regarding gender-affirming care and highlight the current therapeutic and legislative landscapes within the scope of pediatric surgical practice. LEVEL OF EVIDENCE: IV.
Subject(s)
Specialties, Surgical , Surgeons , Transgender Persons , Child , Humans , United States , Gender IdentityABSTRACT
BACKGROUND: Acute arterial thrombosis can be life- and limb-threatening. Most pediatric patients with iliofemoral arterial thrombosis are treated successfully with medical therapy; however, expert consensus is limited, and many recommendations are based on the extrapolation of adult data. We aim to understand treatment patterns and long-term outcomes after pediatric acute iliofemoral arterial thrombosis, from which management recommendations can be informed. METHODS: A single-institution retrospective study of pediatric patients diagnosed with iliofemoral arterial thrombosis from 2009 to 2018 was performed. Multiple parameters of management and follow-up were evaluated. Children anticoagulated for ≤28 days versus >28 days were compared. Data analysis used Fisher exact and Mann-Whitney U tests. RESULTS: Two hundred thirty-six children were included. Median age at diagnosis was 65 days (interquartile range 17-163), with 207 diagnosed as infants, 15 diagnosed between 1 to 2 years, and 14 diagnosed between 2 to 16 years. The median treatment duration was 28 days (interquartile range 13-42); patients treated for >28 days had a longer time for thrombus resolution, and more follow-up ultrasounds were performed. Limb length discrepancy did not differ between the groups (1.0% vs 6.3%, P = .06), and no patients were documented to have developed peripheral arterial disease over a median 6.5-year follow-up. Multiple treatment strategies were employed, the most common being heparin bridged to enoxaparin (25.0%) and enoxaparin monotherapy (21.6%). Eight patients (3.4%) underwent surgical intervention. CONCLUSION: Pediatric iliofemoral arterial thrombosis is primarily a disease of infants treated adequately with heparin or enoxaparin, infrequently requires surgical intervention, and is rarely associated with long-term complications. When guided by thrombus resolution on ultrasound, a four-week or shorter course of anticoagulation does not increase the need for surgical intervention or long-term complications.
Subject(s)
Enoxaparin , Thrombosis , Adult , Infant , Humans , Child , Retrospective Studies , Thrombosis/diagnosis , Thrombosis/etiology , Thrombosis/therapy , Heparin , Blood Coagulation , Treatment OutcomeABSTRACT
INTRODUCTION: Appendicitis is the most common indication for emergency general surgery in the pediatric population. Computed tomography (CT) or magnetic resonance imaging (MRI) may be used for diagnosis when ultrasound findings are equivocal. However, CT involves unnecessary radiation exposure if MRI is available. After introducing a rapid sequence MRI (rsMRI) appendicitis protocol at our institution, CT was still preferentially used. We therefore implemented a quality improvement (QI) campaign to reduce the rate of CTs and increase the rate of rsMRI. Here, we assess the effectiveness of the QI campaign while evaluating potential barriers to using rsMRI. METHODS: We conducted a mixed methods study, first performing stakeholder interviews which informed the design of a QI campaign initiated in May 2021 and a midway feedback survey in December 2021. A retrospective cohort study was then performed of children evaluated for appendicitis at our institution between January 1, 2016, and April 30, 2022. CT and rsMRI rates were compared before and after QI campaign implementation. RESULTS: There was a significant decrease in rate of CTs and increase in rate of rsMRIs performed following the initiation of the QI campaign (p < 0.0001). The rate of CT scans decreased by a factor of 0.4 while the rate of rsMRI increased by a factor of 9.5. CONCLUSION: A successful QI campaign was initiated at our institution, resulting in decreased utilization of CT and increased use of rsMRI for the evaluation of suspected appendicitis. These results highlight the potential impact of QI projects. LEVEL OF EVIDENCE: III.
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OBJECTIVE: The incidence and significance of pneumatosis intestinalis (PI) in children with a diagnosis of intestinal failure is not well understood. The aim of this study was to identify clinical and anatomical factors associated with the imaging findings of PI in patients with intestinal failure. METHODS: We performed a retrospective review of all children with a diagnosis of intestinal failure at Children's Hospital Colorado between January 2019 and April 2022. Patients were stratified and compared based on the incidence of PI on abdominal imaging. Differences were compared using 2-sample Wilcoxon tests, chi-square, or Fisher exact tests. RESULTS: There were 111 patients identified with a diagnosis of intestinal failure and 30.6% (34) developed at least 1 instance of PI. There were no differences in etiology of intestinal failure or anatomy between those who developed PI and those who did not. Patients who developed PI, were less likely to be on total parental nutrition (60.6% vs 98.6%, P < 0.001) and more likely to be receiving any form of enteral feeds (87.9% vs 66.2%, P = 0.035) or tube feeds (75.8% vs 44.2%, P = 0.0045). Of the children with PI, 30.3% (10) were undergoing an enteral feed advancement at time of PI development. Three patients with PI underwent laparotomy for PI treatment, 2 of which were negative laparotomies. CONCLUSIONS: The development of PI in children with intestinal failure is likely a benign finding. It is associated with enteral feeding and may be due to increased intestinal stress.
Subject(s)
Intestinal Failure , Pneumatosis Cystoides Intestinalis , Humans , Child , Enteral Nutrition/adverse effects , Enteral Nutrition/methods , Intestines , Retrospective Studies , Colorado , Pneumatosis Cystoides Intestinalis/diagnostic imaging , Pneumatosis Cystoides Intestinalis/etiologyABSTRACT
INTRODUCTION: Bias and discrimination remain pervasive in the medical field and increase the risk of burnout, mental health disorders, and medical errors. The experiences of APSA members with bias and discrimination are unknown, therefore the APSA committee on Diversity, Equity and Inclusion conducted a survey to characterize the prevalence of bias and discrimination. METHODS: 1558 APSA members were sent an anonymous survey, of which 423 (27%) responded. Respondents were asked about their demographics, knowledge of implicit bias, and experience of bias and discrimination within their primary workplace, APSA, and APSA committees. Data were analyzed using Fisher's Exact test, Kruskal-Wallis test, and multivariable logistic regression as appropriate with significance defined as p<0.05. RESULTS: Discrimination was reported across all levels of practice, academic appointments, race, ethnicity, and gender identities. On multivariable analysis, surgical trainees (OR 3.6) as well as Asian American and Pacific Islander (OR 4.8), Black (OR 5.2), Hispanic (OR 8.2) and women (OR 8.7) surgeons were more likely to experience bias and discrimination in the workplace. Community practice surgeons were more likely to experience discrimination within APSA committees (OR 3.6). Members identifying as Asian (OR 0.4), or women (OR 0.6) were less likely to express comfort reporting instances of bias and discrimination. CONCLUSION: Workplace discrimination exists across all training levels, academic appointments, and racial and gender identities. Trainees and racial- and gender-minority surgeons report disproportionately high prevalence of bias and discrimination. Improving reporting mechanisms and implicit bias training are possible initiatives in addressing these findings.
Subject(s)
Burnout, Professional , Surgeons , Humans , Female , Ethnicity , Surveys and Questionnaires , Hispanic or LatinoABSTRACT
INTRODUCTION: There are existing healthcare disparities in pediatric surgery today. Identity and racial incongruity between patients and providers contribute to systemic healthcare inequities and negatively impacts health outcomes of minoritized populations. Understanding the current demographics of the American Pediatric Surgical Association and therefore the cognitive diversity represented will help inform how best to strategically build the organization to optimize disparity solutions and improve patient care. METHODS: 1558 APSA members were sent an anonymous electronic survey. Comparative data was collected from the US Census Bureau and the Association of American Medical Colleges. Results were analyzed using standard statistical tests. RESULTS: Of 423 respondents (response rate 27%), the race and ethnicity composition were 68% non Hispanic White, 12% Asian American and Pacific Islander, 6% Hispanic, 5% multiracial, and 4% Black/African American. Respondents were 35% women, 63% men, and 1% transgender, androgyne, or uncertain. Distribution of sexual identity was 97% heterosexual and 3% LGBTQIA. Religious identity was 50% Christian, 22% Agnostic/Atheist, 11% Jewish, 3% Hindu, and 2% Muslim. 32% of respondents were first-generation Americans. Twenty-four different primary languages were spoken, and 46% of respondents were conversational in a second language. These findings differ in meaningful ways from the overall American population and from the population of matriculants in American medical schools. CONCLUSION: There are substantial differences in the racial, gender, and sexual identity composition of APSA members compared with the overall population in the United States. To achieve excellence in patient care and innovate solutions to existing disparities, representation, particularly in leadership is essential. TYPE OF STUDY: Survey; original research. LEVEL OF EVIDENCE: Level IV.
Subject(s)
Ethnicity , Hispanic or Latino , Male , Child , Humans , Female , United States , Racial Groups , Black or African American , Healthcare DisparitiesABSTRACT
BACKGROUND: Operating room (OR) costs account for 40% of hospital costs. Disposable supplies make up a portion of OR costs and are the only cost that is under control of the surgeon. There are little data to explain how surgeons select surgical supplies and what factors predict supply selection. Our goal with the current work was to assess variation in cost of disposable OR supplies at the surgeon level, hypothesizing high variability would be observed. STUDY DESIGN: Cost data were reviewed for the most common procedures performed by five surgical divisions at a single children's hospital over a six-month period in 2021. For each procedure, the average disposable OR costs for each surgeon were tabulated and compared to the median supply cost for a given procedure at the group level. RESULTS: For each procedure, the variation ranged from 149% (gastrostomy tube placement) to 758% (tonsillectomy and adenoidectomy). The median supply cost for an individual surgeon was not always above or below the median supply cost for that procedure for the group. No relationship was observed between whether the supply cost was above or below the median for a given case and a surgeon's case volume, years in practice, or operative length. There was also no relationship between surgeon volume and median cost, surgery length, and years of experience. CONCLUSION: These data demonstrate variation in the cost of disposable OR supplies at the individual surgeon level at a single institution. This variation is not explained by case volume, years in practice, or operative length.
Subject(s)
Operating Rooms , Surgeons , Humans , Child , Hospital Costs , Adenoidectomy , Hospitals, Pediatric , Disposable EquipmentABSTRACT
Organometallic complexes are the basis for homogeneous catalysis, have applications in materials science and are also active pharmaceutical ingredients. The interaction between transition metal complexes in the solid state is determining their thermodynamics and bio-availability. Non-covalent interactions such as hydrogen bonding and van der Waals are stabilizing crystals of transition metal complexes. The variation of ligand field, central metal atoms and their oxidation and spin states are determinants of the magnitude of their inter-molecular interactions. A comparison of a set of 43 manually curated experimental heats of sublimation (the new XTMC43 set) and results from periodic DFT calculations shows that an agreement to within 9% can be achieved using GGA or mGGA functionals with atom-centred Gaussian-type basis functions. The need for careful assessments of consistency, calibration and reproducibility of experimental and computational data is discussed. Results regarding the new XTMC43 benchmark set are suggested to serve as a starting point for further method development, systematic screening and crystal engineering.
Subject(s)
Coordination Complexes , Transition Elements , Benchmarking , Reproducibility of Results , Thermodynamics , Hydrogen Bonding , Transition Elements/chemistryABSTRACT
PURPOSE: The use of lung ultrasound for diagnosis of COVID-19 has emerged during the pandemic as a beneficial diagnostic modality due to its rapid availability, bedside use, and lack of radiation. This study aimed to determine if routine ultrasound (US) imaging of the lungs of trauma patients with COVID-19 infections who undergo extended focused assessment with sonography for trauma (EFAST) correlates with computed tomography (CT) imaging and X-ray findings, as previously reported in other populations. METHODS: This was a prospective, observational feasibility study performed at two level 1 trauma centers. US, CT, and X-ray imaging were retrospectively reviewed by a surgical trainee and a board-certified radiologist to determine any correlation of imaging findings in patients with active COVID-19 infection. RESULTS: There were 53 patients with lung US images from EFAST available for evaluation and COVID-19 testing. The overall COVID-19 positivity rate was 7.5%. COVID-19 infection was accurately identified by one patient on US by the trainee, but there was a 15.1% false-positive rate for infection based on the radiologist examination. CONCLUSIONS: Evaluation of the lung during EFAST cannot be used in the trauma setting to identify patients with active COVID-19 infection or to stratify patients as high or low risk of infection. This is likely due to differences in lung imaging technique and the presence of concomitant thoracic injury.
Subject(s)
COVID-19 , Focused Assessment with Sonography for Trauma , Lung Diseases , Lung , Wounds and Injuries , COVID-19/complications , COVID-19/diagnostic imaging , COVID-19/epidemiology , False Positive Reactions , Feasibility Studies , Humans , Lung/diagnostic imaging , Lung Diseases/diagnostic imaging , Lung Diseases/etiology , Pandemics , Prospective Studies , Retrospective Studies , SARS-CoV-2 , Sensitivity and Specificity , Tomography, X-Ray Computed , Trauma Centers , Wounds and Injuries/complications , Wounds and Injuries/diagnostic imagingABSTRACT
PURPOSE: Adoption of telemedicine (TME) in surgical specialties, prior to the COVID-19 pandemic, has previously been slow. The purpose of this prospective, observational, single institution study is to evaluate surgeon and caregiver perspectives of TMEs during the pandemic. METHODS: Surveys were distributed to surgical faculty regarding perceptions of TME early during the pandemic and 2 months later. Caregivers (or patients > 18 years old) were asked after each TME to complete a survey regarding perceptions of TMEs. RESULTS: Surveys were distributed to 73 surgeons. Response rates were 71% initially and 63% at follow-up. Sixty-eight percent reported no prior TME experience. No significant differences were noted in the overall satisfaction. An inverse relationship between surgeon age and satisfaction at the follow-up survey was identified (p = 0.007). Additional surveys were distributed to 616 caregivers or patients (response rate 13%). Seventy-two percent reported no prior experience with TME and 79% described TME as similar to an in-person visit. Audiovisual satisfaction of the TME was higher in greater income households (p = 0.02). CONCLUSIONS: Pre-pandemic experience with TME was low in both groups; however, experiences were perceived as satisfactory. Positive experiences with TME may encourage increased utilization in the future, although demographic variations may impact satisfaction with TME. TRIAL REGISTRATION: Unique identifier NCT04376710 at Clinicaltrials.gov (5/6/2020).
Subject(s)
COVID-19 , Surgeons , Telemedicine , Adolescent , Caregivers , Child , Humans , Pandemics , Patient Satisfaction , Prospective Studies , SARS-CoV-2ABSTRACT
BACKGROUND: Pediatric surgeons are often asked to treat clinical problems for which little high-quality data exist. For adults with adhesive small bowel obstruction (ASBO), water soluble contrast-based protocols are used to guide management. Little is known about their utility in children. We aimed to better understand key factors in clinical decision-making processes and integration of adult based data in pediatric surgeon's approach to ASBO. METHODS: We administered a web-based survey to practicing pediatric surgeons at institutions comprising the Western Pediatric Surgery Research Consortium. RESULTS: The response rate was 69% (78/113). Over half of respondents reported using contrast protocols to guide ASBO management either routinely or occasionally (n = 47, 60%). Common themes regarding the incorporation of adult-based data into clinical practice included the need to adapt protocols for pediatric patients, the dearth of pediatric specific data, and the quality of the published adult evidence. CONCLUSIONS: Our findings demonstrate that pediatric surgeons use contrast-based protocols for the management of ASBO despite the paucity of pediatric specific data. Furthermore, our survey data help us understand how pediatric surgeons incorporate adult based evidence into their practice.
Subject(s)
Decision Making , Intestinal Obstruction , Surgeons , Adhesives , Adult , Attitude of Health Personnel , Child , Humans , Intestinal Obstruction/diagnostic imaging , Intestinal Obstruction/surgery , Surveys and Questionnaires , Tissue Adhesions/diagnostic imaging , Tissue Adhesions/surgeryABSTRACT
Infantile myofibromatosis is a rare myofibroblastic proliferative disorder characterized by firm, skin-colored to red-purple cutaneous and subcutaneous nodules; these are the most prevalent fibrous tumors observed in infancy. A premature male infant presented at birth with multiple subcutaneous firm skin-colored nodules measuring about 1-2cm each. Full body MRI and excisional biopsy of the right chest nodule confirmed the diagnosis. We review the case of infantile myofibromatosis and discuss its highly heterogeneous presentation and clinical course, as well as histopathology, genetic testing, and approaches to management.
Subject(s)
Myofibromatosis/congenital , Head and Neck Neoplasms/congenital , Head and Neck Neoplasms/pathology , Humans , Infant, Newborn , Infant, Premature , Male , Myofibromatosis/genetics , Myofibromatosis/pathology , Photography , ScalpABSTRACT
PURPOSE: Previously, we demonstrated enhanced adaptation after small bowel resection (SBR) in intestinal-specific retinoblastoma (Rb)-deficient mice along with elevated levels of insulin-like growth factor 2 (IGF2) expression within the villi. The purpose of this study was to verify that the insulin-like growth factor 1 receptor (IGF1R) plays a role in this phenomenon. METHODS: Inducible and intestinal specific Rb and IGF1R double knockout mice (iRb/IGF1R-IKO) (n=4) and Rb single knockout mice (iRb-IKO) (n=5) underwent 50% mid SBR. On post-operative day 28, mice were harvested, and structural adaptation was measured as changes in crypt depth and villus height. Rates of enterocyte proliferation were recorded. IGF2 expression within the remnant villi was measured via RT-PCR. RESULTS: Both iRb-IKO and iRb/IGF1R-IKO mice demonstrated enhanced adaptation with at least a 45% increase in both crypt depth and villus height in the proximal and distal remnant bowel. Both groups showed elevation of IGF2 expression in the remnant villi, but there were no differences between the two groups. CONCLUSION: Epithelial IGF1R is dispensable for IGF2-mediated enhanced intestinal adaptation in retinoblastoma-deficient mice. Our findings suggest that IGF2 signals for enhanced adaptation in cells outside of the epithelium. Further investigation is needed to study the IGF2/IGF1R signaling interaction within the mesenchyme. LEVEL OF EVIDENCE: Animal study - not clinical.
Subject(s)
Adaptation, Physiological , Insulin-Like Growth Factor II/metabolism , Intestinal Mucosa/metabolism , Intestine, Small/surgery , Receptor, IGF Type 1/metabolism , Retinoblastoma Protein/deficiency , Short Bowel Syndrome/metabolism , Animals , Biomarkers/metabolism , Intestinal Mucosa/physiology , Intestine, Small/metabolism , Intestine, Small/physiology , Mice , Mice, Knockout , Postoperative Period , Real-Time Polymerase Chain Reaction , Short Bowel Syndrome/physiopathologyABSTRACT
PURPOSE: Intestinal adaptation structurally represents increases in crypt depth and villus height in response to small bowel resection (SBR). Previously, we found that neither epidermal growth factor receptor (EGFR) nor insulin-like growth factor 1 receptor (IGF1R) function was individually required for normal adaptation. In this study, we sought to determine the effect of disrupting both EGFR and IGF1R expression on resection-induced adaptation. METHODS: Intestinal-specific EGFR and IGF1R double knockout mice (EGFR/IGF1R-IKO) (n=6) and wild-type (WT) control mice (n=7) underwent 50% proximal SBR. On postoperative day (POD) 7, structural adaptation was scored by measuring crypt depth and villus height. Rates of crypt cell proliferation, apoptosis, and submucosal capillary density were also compared. RESULTS: After 50% SBR, normal adaptation occurred in both WT and EGFR/IGF1R-IKO. Rates of proliferation and apoptosis were no different between the two groups. The angiogenic response was less in the EGFR/IGF1R-IKO compared to WT mice. CONCLUSION: Disrupted expression of EGFR and IGF1R in the intestinal epithelial cells does not affect resection-induced structural adaptation but attenuates angiogenesis after SBR. These findings suggest that villus growth is driven by receptors and pathways that occur outside the epithelial cell component, while angiogenic responses may be influenced by epithelial-endothelial crosstalk.
Subject(s)
Adaptation, Physiological , ErbB Receptors/metabolism , Intestine, Small/physiology , Intestine, Small/surgery , Receptor, IGF Type 1/metabolism , Animals , Apoptosis , Cell Proliferation , Epithelial Cells/physiology , Intestinal Mucosa/metabolism , Intestine, Small/blood supply , Mice, Knockout , Neovascularization, PhysiologicABSTRACT
PURPOSE: Intestinal adaptation involves villus lengthening, crypt deepening, and increased capillary density following small bowel resection (SBR). Mice lacking the proangiogenic chemokine CXCL5 have normal structural adaptation but impaired angiogenesis. This work evaluates the impact of incomplete adaptive angiogenesis on the functional capacity of the intestine after SBR. METHODS: CXCL5 knockout (KO) and C57BL/6 wild-type (WT) mice underwent 50% SBR. Magnetic resonance imaging measured weekly body composition. Intestinal absorptive capacity was evaluated through fecal fat analysis. Gene expression profiles for select macronutrient transporters were measured via RT-PCR. Postoperative crypt and villus measurements were assessed for structural adaptation. Submucosal capillary density was measured through CD31 immunohistochemistry. RESULTS: Comparable postoperative weight gain occurred initially. Diminished weight gain, impaired fat absorption, and elevated steatorrhea occurred in KO mice after instituting high-fat diet. Greater postoperative upregulation of ABCA1 fat transporter occurred in WT mice, while PEPT1 protein transporter was significantly downregulated in KO mice. KO mice had impaired angiogenesis but intact structural adaptation. CONCLUSION: After SBR, KO mice display an inefficient intestinal absorption profile with perturbed macronutrient transporter expression, impaired fat absorption, and slower postoperative weight gain. In addition to longer villi and deeper crypts, an intact angiogenic response may be required to achieve functional adaptation to SBR.
Subject(s)
Adaptation, Physiological , Intestine, Small/blood supply , Intestine, Small/surgery , Neovascularization, Physiologic , Animals , Chemokine CXCL5 , Intestinal Absorption , Intestinal Mucosa/pathology , Intestine, Small/physiology , Mice, Inbred C57BL , Mice, KnockoutABSTRACT
INTRODUCTION: Short bowel syndrome (SBS) is a morbid clinical condition that results from massive small-bowel resection (SBR). After SBR, there is a dramatic weight loss in the acute postoperative period. Our aim was to determine the impact of a high-protein diet (HPD) on weight gain and body composition in mice after SBR. METHODS: C57BL/6 mice underwent 50 % proximal SBR. Postoperatively, mice were randomly selected to receive standard rodent liquid diet (LD) (n = 6) or an isocaloric HPD (n = 9) for 28 days. Mice weights were recorded daily. Body composition analyses were obtained weekly. Student's t test was used for statistical comparisons with p < 0.05 considered significant. RESULTS: Mice that were fed HPD after SBR returned to baseline weight on average at postoperative day (POD) 8 versus mice that were fed LD that returned to baseline weight on average at POD 22. Total fat mass and lean mass were significantly greater by POD 14 within the HPD group. Both groups of mice demonstrated normal structural adaptation. CONCLUSION: HPD results in greater weight gain and improved body composition in mice after SBR. This finding may be clinically important for patients with SBS since improved weight gain may reduce the time needed for parenteral nutrition.