Tissue engineering and regenerative medicine approaches in colorectal surgery.

Tissue engineering and regenerative medicine (TERM) is an emerging field that has provided new therapeutic opportunities by delivering innovative solutions. The development of nontraditional therapies for previously unsolvable diseases and conditions has brought hope and excitement to countless individuals globally. Many regenerative medicine therapies have been developed and delivered to patients clinically. The technology platforms developed in regenerative medicine have been expanded to various medical areas; however, their applications in colorectal surgery remain limited. Applying TERM technologies to engineer biological tissue and organ substitutes may address the current therapeutic challenges and overcome some complications in colorectal surgery, such as inflammatory bowel diseases, short bowel syndrome, and diseases of motility and neuromuscular function. This review provides a comprehensive overview of TERM applications in colorectal surgery, highlighting the current state of the art, including preclinical and clinical studies, current challenges, and future perspectives. This article synthesizes the latest findings, providing a valuable resource for clinicians and researchers aiming to integrate TERM into colorectal surgical practice.

Does the Timing of Surgical Intervention Impact Outcomes in Necrotizing Enterocolitis?

OBJECTIVES: The optimal time for intervention in surgical necrotizing enterocolitis (sNEC) remains to be elucidated. Surgical management varies between peritoneal drain (PD), laparotomy (LAP), and PD with subsequent LAP (PD + LAP). We propose that some infants with surgical NEC benefit from late (>48 h) operative intervention to allow for resuscitation. METHODS: A retrospective comparison of clinical information in infants with sNEC from 2012 to 2022 was performed. Early intervention was defined as less than 48 hours from time of NEC diagnosis to surgical intervention. RESULTS: 118 infants were identified, 92 underwent early intervention (62 LAP; 22 PD; 8 PD + LAP) and 26 underwent late intervention (20 LAP; 2 PD; 4 PD + LAP). Infants with early intervention were diagnosed younger (DOL 8 [6, 15] vs 20 [11, 26]; P=< .05) with more pneumoperitoneum (76% vs 23%; P=< .05). The early intervention group had a higher mortality (35% vs 15%; P=< .05). When excluding infants with pneumoperitoneum, the early intervention group had a higher mortality rate (10/22 (45%), 4/26 (15%); P < .05) and had more bowel resected (29 ± 17 cm vs 9 ± 8 cm; P < .05), with the same number of patients scoring above 3 on the MD7 criteria. CONCLUSION: Infants with NEC who underwent early surgical intervention had a higher mortality and more bowel resected. While this study has a provocative finding, it is severely limited by the non-specific 48-hour cut off. However, our data suggests that a period of medical optimization may improve outcomes in infants with sNEC and thus more in-depth studies are needed.

Clinical Correlates of Cholestasis in Preterm Infants with Surgical Necrotizing Enterocolitis.

Background: We sought to investigate the clinical determinants and outcomes of cholestasis in preterm infants with surgical necrotizing enterocolitis (sNEC). Methods: Retrospective comparison of clinical information in preterm infants who developed cholestasis vs those who did not. Results: Sixty-two (62/91, 68.1%) infants with NEC developed cholestasis at any time following the onset of illness. Cholestasis was seen more frequently in those who had received ionotropic support at 24 hours following sNEC diagnosis (87.1% vs 58.6%; p = 0.002), had higher mean C-reactive protein levels 2 weeks after NEC diagnosis (p = 0.009), had blood culture-positive sepsis [25 (40.3%) vs 4 (13.8%); p = 0.011], received parenteral nutrition (PN) for longer durations (108.4 ± 56.63 days vs 97.56 ± 56.05 days; p = 0.007), had higher weight-for-length z scores at 36 weeks' postmenstrual age [-1.0 (-1.73, -0.12) vs -1.32 (-1.76, -0.76); p = 0.025], had a longer length of hospital stay (153.7 ± 77.57 days vs 112.51 ± 85.22 days; p = 0.024), had intestinal failure more often (61% vs 25.0%, p = 0.003), had more surgical complications (50% vs 27.6%; p = 0.044), and had >1 complication (21% vs 3.4%; p = 0.031). Using linear regression, the number of days after surgery when feeds could be started [OR 15.4; confidence interval (CI) 3.71, 27.13; p = 0.009] and the postoperative ileus duration (OR 11.9, CI 1.1, 22.8; p = 0.03) were independently associated with direct bilirubin between 2 and 5 mg/dL (mild-moderate cholestasis) at 2 months of age. The duration of PN was independently associated with direct bilirubin >5 mg/dL (severe cholestasis) at 2 months of age in these patients. Conclusion: Cholestasis was seen in 68% of infants following surgical NEC. The most likely contributive factors are intestinal failure and subsequent PN dependence for longer periods. Our data suggest that identification and prevention of risk factors such as sepsis and surgical complications and early feeds following NEC surgery may improve outcomes.

Gastroschisis for the Gastroenterologist: Updates on Epidemiology, Management, and Outcomes.

Gastroschisis is a common congenital abdominal wall defect, likely influenced by environmental factors in utero, with increasing prevalence in the United States. Early detection of gastroschisis in utero has become the standard with improved prenatal care and screening. There are multiple surgical management techniques, though sutureless closure is being used more frequently. Postoperative feeding difficulty is common and requires vigilance for complications, such as necrotizing enterocolitis. Infants with simple gastroschisis are expected to have eventual catch-up growth and normal development, while those with complex gastroschisis have higher morbidity and mortality. Management requires collaboration amongst several perinatal disciplines, including obstetrics, maternal fetal medicine, neonatology, pediatric surgery, and pediatric gastroenterology for optimal care and long-term outcomes.

Toll Like Receptor 4 Mediated Lymphocyte Imbalance Induces Nec-Induced Lung Injury.

Necrotizing enterocolitis (NEC) is the leading cause of death from gastrointestinal disease in premature infants, and is associated with the development of severe lung inflammation. The pathogenesis of NEC-induced lung injury remains unknown, yet infiltrating immune cells may play a role. In support of this possibility, we now show that NEC in mice and humans was associated with the development of profound lung injury that was characterized by an influx of Th17 cells and a reduction in T regulatory lymphocytes (Tregs). Importantly, the adoptive transfer of CD4 T cells isolated from lungs of mice with NEC into the lungs of immune incompetent mice (Rag1 mice) induced profound inflammation in the lung, while the depletion of Tregs exacerbated NEC induced lung injury, demonstrating that imbalance of Th17/Treg in the lung is required for the induction of injury. In seeking to define the mechanisms involved, the selective deletion of toll-like receptor 4 (TLR4) from the Sftpc1 pulmonary epithelial cells reversed lung injury, while TLR4 activation induced the Th17 recruiting chemokine (C-C motif) ligand 25 (CCL25) in the lungs of mice with NEC. Strikingly, the aerosolized inhibition of both CCL25 and TLR4 and the administration of all trans retinoic acid restored Tregs attenuated NEC-induced lung injury. In summary, we show that TLR4 activation in Surfactant protein C-1 (Sftpc1) cells disrupts the Treg/Th17 balance in the lung via CCL25 leading to lung injury after NEC and reveal that inhibition of TLR4 and stabilization of Th17/Treg balance in the neonatal lung may prevent this devastating complication of NEC.

Evaluation of Anemia and Nutritional Status on Children Undergoing Resection of Primary Liver Tumors.

INTRODUCTION: Complete tumor resection of primary malignant liver tumors offers the best chance of survival. However, many of these children may experience anemia and failure to thrive. This study analyzes the association of preoperative anemia and nutritional support with outcomes in children undergoing major resection of primary malignant liver tumors. METHODS: Using the National Surgical Quality Improvement Program Pediatric database from 2012 to 2015, children undergoing major liver resections for primary malignant hepatic tumors were selected. Patient demographics, comorbidities, and 30-d outcomes were compared with respect to the presence of preoperative anemia and the need for nutritional support. Outcomes included 30-d postoperative complications, perioperative blood transfusions, and hospital readmissions. Propensity score matching was performed to control for significant confounders. RESULTS: One hundred ten children were included, 76 (69.1%) with preoperative anemia, and 36 (32.7%) receiving nutritional support. Anemia was associated with preoperative chemotherapy (P = 0.02) and steroids (P = 0.03). Nutritional support was associated with cardiac (P = 0.01), respiratory (P < 0.01), neurologic (P < 0.01), and hematologic comorbidities (P = 0.02). There were 20 (18.2%) postoperative complications and 6 (5.5%) hospital readmissions. After propensity score matching, there was no difference in complications between anemic and nonanemic patients (P = 0.13). Preoperative nutritional support was associated with an increased rate of complications (P < 0.01). Neither anemia (P = 1.00) nor nutritional support (P = 0.49) were associated with readmissions. CONCLUSIONS: The need for nutritional support is common in children undergoing resection of primary malignant hepatic tumors. Anemia was not significantly associated with postoperative complications. In this study, nutritional support was associated with an increased risk of postoperative complications. The need for nutritional support may warrant special attention to the patient's overall conditioning during operative planning.

Analysis of risk factors for morbidity in children undergoing the Kasai procedure for biliary atresia.

OBJECTIVE: To evaluate the perioperative risk factors for 30-day complications of the Kasai procedure in a large, cross-institutional, modern dataset. STUDY DESIGN: The 2012-2015 National Surgical Quality Improvement Program Pediatric database was used to identify patients undergoing the Kasai procedure. Patients' characteristics were compared by perioperative blood transfusions and 30-day outcomes, including complications, reoperations, and readmissions. Multivariable logistic regression was used to identify risk factors predictive of outcomes. Propensity matching was performed for perioperative blood transfusions to evaluate its effect on outcomes. RESULTS: 190 children were included with average age of 62 days. Major cardiac risk factors were seen in 6.3%. Perioperative blood transfusions occurred in 32.1%. The 30-day post-operative complication rate was 15.8%, reoperation 6.8%, and readmission 15.3%. After multivariate analysis, perioperative blood transfusions (OR 3.94; p < 0.01) and major cardiac risk factors (OR 7.82; p < 0.01) were found to increase the risk of a complication. Perioperative blood transfusion (OR 4.71; p = 0.01) was associated with an increased risk of reoperation. Readmission risk was increased by prematurity (OR 3.88; p = 0.04) and 30-day complication event (OR 4.09; p = 0.01). After propensity matching, perioperative blood transfusion was associated with an increase in complications (p < 0.01) and length of stay (p < 0.01). CONCLUSION: Major cardiac risk factors and perioperative blood transfusions increase the risk of post-operative complications in children undergoing the Kasai procedure. Further research is warranted in the perioperative use of blood transfusions in this population. LEVEL OF EVIDENCE: IV.

Process measures facilitate maturation of pediatric enhanced recovery protocols.

BACKGROUND/PURPOSE: The role of process measures used to predict quality in pediatric colorectal surgery enhanced recovery protocols has not been described. The purpose of this study was to demonstrate the feasibility of abstracting and monitoring process measures over protocol improvement iteration. METHODS: Patients enrolled in the Pediatric Colorectal Enhanced Recovery After Surgery pathway at our institution were grouped by stage of implementation. We used a quality improvement database to compare multistage enhanced recovery process measures and 30-day patient outcomes. RESULTS: We identified 58 surgical patients with 28(48%) cases enrolled in the pathway. There was increased use of regional anesthesia techniques in pathway patients (83% versus 20%, p < 0.001). All preoperative process measures clinically improved between early and full implementation. Improvements included a dramatic increase in formal preoperative education (56% versus 0%, p = 0.004) and administration of preoperative medication (p = 0.025). Overall, 12 (21%) patients experienced postoperative complications, which were similarly distributed between implementation groups. Readmissions were highest during the early implementation phase (40%, p = 0.029). Children in the late implementation group experienced fewer complications, which clinically correlated with process measure adherence. CONCLUSIONS: Process measures complement outcome measures in assessing quality and effectiveness of a pediatric colorectal recovery protocol. Adherence to processes may reduce complications. LEVEL OF EVIDENCE: Treatment study, Level III.

Malnutrition increases the risk of 30-day complications after surgery in pediatric patients with Crohn disease.

BACKGROUND: Pediatric patients with Crohn disease (CD) are frequently malnourished, yet how this affects surgical outcomes has not been evaluated. This study aims to determine the effects of malnourishment in children with CD on 30-day outcomes after surgery. STUDY DESIGN: The ACS NSQIP-Pediatric database from 2012 to 2015 was used to select children aged 5-18 with CD who underwent bowel surgery. BMI-for-age Z-scores were calculated based on CDC growth charts and 2015 guidelines of pediatric malnutrition were applied to categorize severity of malnutrition into none, mild, moderate, or severe. Malnutrition's effects on 30-day complications. Propensity weighted multivariable regression was used to determine the effect of malnutrition on complications were evaluated. RESULTS: 516 patients were included: 349 (67.6%) without malnutrition, 97 (18.8%) with mild, 49 (9.5%) with moderate, and 21 (4.1%) with severe malnutrition. There were no differences in demographics, ASA class, or elective/urgent case type. Overall complication rate was 13.6% with malnutrition correlating to higher rates: none 9.7%, mild 18.6%, moderate 20.4%, and severe 28.6% (p < 0.01). In propensity-matched, multivariable analysis, malnutrition corresponded with increased odds of complications in mild and severely malnourished patients (mild OR = 2.1 [p = 0.04], severe OR 3.26 [p = 0.03]). CONCLUSION: Worsening degrees of malnutrition directly correlate with increasing risk of 30-day complications in children with CD undergoing major bowel surgery. These findings support BMI for-age z scores as an important screening tool for preoperatively identifying pediatric CD patients at increased risk for postoperative complications. Moreover, these scores can guide nutritional optimization efforts prior to elective surgery. LEVEL OF EVIDENCE: IV.

Who was Dr. William C. Baum?

The first discovery of primary hyperaldosteronism secondary to an aldosterone-secreting adrenal adenoma has been credited solely to Dr. Jerome Conn, an endocrinologist at the University of Michigan and for whom, Conn syndrome was named. Dr. William Baum, a urologist at the University of Michigan, however, was instrumental in the appropriate operation and historical aldosteronoma resection. Despite Dr. Baum's important role in this discovery, he was never included as an author in any of the subsequent papers describing Conn syndrome and, few today would recognize his name. So, who was Dr. Baum and what happened? This historical article aims to revisit the history surrounding the discovery of aldosteronoma as a cause of Conn's syndrome and to catalog the life and involvement of Dr. William C. Baum in that discovery.

Survey of the American Pediatric Surgical Association on cannulation practices in pediatric ECMO.

AIMS: Extracorporeal membrane oxygenation (ECMO) is a commonly used modality of life support for children with cardiopulmonary failure. Consensus on pediatric cannulation strategies and management does not currently exist. The goal of this study was to investigate individual surgeon approaches towards ECMO cannulations in children. METHODS: A 21-question online survey was developed and disseminated to the American Pediatric Surgical Association (APSA) membership. Participant responses were summarized as counts and percentages. Effect of ECMO volume and surgeon experience on responses was assessed. RESULTS: There were 252 APSA members who participated in this study for a response rate of 21%, with 225 (89.3%) performing ECMO. Sixty respondents (28.3%) reported using neck vessels exclusively for cannulation regardless of age or weight of the patient. After neck decannulation, 13 (6.6%) repaired the carotid artery for all patients, and 21 (10.7%) repaired only for children older than 5years. Of those performing femoral cannulation, 56 (26.4%) would perform at 5years or older and 66 (31.1%) at 12years. The most common challenge for femoral cannulation was the need for distal perfusion (n=119; 59.8%). Assistance from vascular surgery was requested by 32 (16.4%) for distal perfusion catheter placement, and by 79 (40.5%) for decannulation. Regarding femoral cannulation, lack of training was more likely to be a challenge if performing <5 cannulations per year (25.2% vs 12.5%; p=0.03). Surgeons with <10years of experience were more likely to consult vascular surgery compared to those with >10years of experience (18.5% vs 8%; p=0.03). CONCLUSION: Considerable variation exists in individual surgeon cannulation practices in pediatric ECMO, in particular in the management of school age and adolescent VA ECMO. Mixed approaches across several ECMO management case study questions indicate that further work is needed to evaluate specific risks with cannulations in children. LEVEL OF EVIDENCE: IV.

Tissue engineering for the treatment of short bowel syndrome in children.

Short bowel syndrome is a major cause of morbidity and mortality in children. Despite decades of experience in the management of short bowel syndrome, current therapy is primarily supportive. Definitive treatment often requires intestinal transplantation, which is associated with significant morbidity and mortality. In order to develop novel approaches to the treatment of short bowel syndrome, we and others have focused on the development of an artificial intestine, by placing intestinal stem cells on a bioscaffold that has an absorptive surface resembling native intestine, and taking advantage of neovascularization to develop a blood supply. This review will explore recent advances in biomaterials, vascularization, and progress toward development of a functional epithelium and mesenchymal niche, highlighting both success and ongoing challenges in the field.

Intraluminal Meckel's Duplication Cyst Causing Bowel Obstruction in an Infant: A Role for Laparotomy.

This report describes a two-month-old girl who presented with signs and symptoms of a distal small bowel obstruction. She underwent an abdominal ultrasound that revealed a right lower quadrant cystic mass. A Technetium-99 scan revealed increased activity in the right lower quadrant consistent with a Meckel's diverticulum. Following a nondiagnostic laparoscopic evaluation, a laparotomy was performed to allow direct palpation of the small bowel and colon. Direct palpation of the ileum revealed a soft intraluminal mass at the ileocecal valve. The child underwent an ileocecectomy and anastomosis incorporating the intraluminal mass. Pathologic analysis revealed an intraluminal enteric duplication cyst containing ectopic gastric mucosa. This case represents the first report of such an entity in an infant. A discussion of the diagnostic and therapeutic aspects of the case and enteric duplication cysts is provided.

Generation of an artificial intestine for the management of short bowel syndrome.

PURPOSE OF REVIEW: This article discusses the current state of the art in artificial intestine generation in the treatment of short bowel syndrome. RECENT FINDINGS: Short bowel syndrome defines the condition in which patients lack sufficient intestinal length to allow for adequate absorption of nutrition and fluids, and thus need parenteral support. Advances toward the development of an artificial intestine have improved dramatically since the first attempts in the 1980s, and the last decade has seen significant advances in understanding the intestinal stem cell niche, the growth of complex primary intestinal stem cells in culture, and fabrication of the biomaterials that can support the growth and differentiation of these stem cells. There has also been recent progress in understanding the role of the microbiota and the immune cells on the growth of intestinal cultures on scaffolds in animal models. Despite recent progress, there is much work to be done before the development of a functional artificial intestine for short bowel syndrome is successfully achieved. SUMMARY: Continued concerted efforts by cell biologists, bioengineers, and clinician-scientists will be required for the development of an artificial intestine as a clinical treatment modality for short bowel syndrome.

Subclavian carotid bypass of occluded common and internal carotid arteries facilitated by an anomalous branch of the internal carotid artery.

Typically, internal carotid artery (ICA) occlusion precludes carotid endarterectomy. Extracranial branches of the ICA are uncommon. If this anomaly occurs in the setting of total proximal ICA occlusion then revascularization is feasible. We describe a unique example of such a case.

Comparing the cost and outcomes of laparoscopic versus open appendectomy for perforated appendicitis in children.

Although laparoscopic appendectomy (LA) is accepted treatment for perforated appendicitis (PA) in children, concerns remain whether it has equivalent outcomes with open appendectomy (OA) and increased cost. A retrospective review was conducted of patients younger than age 17 years treated for PA over a 12.5-year period at a tertiary medical center. Patient characteristics, preoperative indices, and postoperative outcomes were analyzed for patients undergoing LA and OA. Of 289 patients meeting inclusion criteria, 86 had LA (29.8%) and 203 OA (70.2%), the two groups having equivalent patient demographics and preoperative indices. Inpatient costs were not significantly different between LA and OA. LA had a lower rate of wound infection (1.2 vs. 8.9%, P = 0.017), total parenteral nutrition use (23.3 vs. 50.7%, P < 0.0001), and length of stay (5.56 ± 2.38 days vs. 7.25 ± 3.77 days, P = 0.0001). There was no significant difference in the rate of postoperative organ space abscess, surgical re-exploration, or rehospitalization. In children with PA, LA had fewer surgical site infections and shorter lengths of hospital stay compared with OA without an increase in inpatient costs.

Computerized tomography in the workup of pediatric appendicitis: why are children scanned?

Physicians increasingly use computerized tomography (CT) for the evaluation of suspected acute appendicitis (AA) in children despite increasing awareness of the potential dangers of CT-associated radiation exposure. Many studies demonstrate the value of CT in the diagnosis of AA, but none have determined what factors influence the decision to perform a CT. We investigated factors associated with the use of CT during initial workup of children who subsequently underwent appendectomy. This is a retrospective review of all patients aged 0 to 17 years who underwent appendectomy for AA by pediatric surgeons over 11 years. Both univariate and multivariable logistic regression models were created to predict use of CT. A total of 546 children underwent appendectomy for AA, of which 293 (53%) underwent CT. In univariate analysis, seven variables were significantly associated with the use of CT: female gender, Hispanic ethnicity, initial presentation to referring hospitals, lower Alvarado scores, delays from onset of symptoms to hospital presentation, migration, and rebound tenderness. In multivariable analysis, four variables significantly independently predicted the use of CT: initial presentation to a referring hospital [odds ratio (OR) 3.50), female gender (OR 1.49), increased latency from symptom onset to presentation (OR 1.34), and the presence of rebound tenderness (OR 0.23), which had a protective effect; the overall model was statistically significant (P < 0.0001). This model is the first to define variables that significantly predict CT utilization in the pediatric population. Continued investigation will be necessary to develop effective algorithms for judicious use of CT for suspected AA.

Computerized tomography utilization in children with appendicitis-differences in referring and children's hospitals.

Increasingly, physicians rely on computerized tomography (CT) to aid in the workup of acute appendicitis (AA) in children despite the potential negative effects of CT-associated radiation exposure. Few studies have investigated the context or location in which the decision to perform CT for AA is made. We sought to determine where the decision to use CT was made during the initial workup of pediatric patients who later underwent an appendectomy. We reviewed the medical record of all patients at a children's hospital (CH) receiving appendectomy over 10.5 years. We abstracted clinical variables using an established clinical AA scoring system, demographics and outcome variables. Patients who underwent CT were compared with those who did not. Additionally, we identified the location where the CT was performed. Our children's hospital was compared with referring hospitals (RHs) with regard to utilization of CT imaging. Five hundred and forty-six patients underwent appendectomy for AA at CH. Of these, 50 per cent underwent CT. Patients who initially presented at the RHs underwent CT at a significantly higher rate than those first presenting to CH (P < 0.0001). Moreover, we found that unlike at the RHs, patients with a higher AA score underwent CT at CH less often (P < 0.0002). RHs used CT more often than CH to diagnose AA in our cohort. CH avoided CT for patients with higher Alvarado scores. Further research is needed to elucidate factors that lead healthcare providers to use CT for children with suspected AA to eliminate unnecessary CT-associated radiation exposure.