Children undergoing early liver re-transplantation for primary non-function have improved survival.

BACKGROUND: Primary non-function (PNF) in the early post-LT period in children leads to prolonged hospitalization, high graft loss, and significant mortality. However, there is a paucity of data available on the natural history of children relisted for LT due to PNF, including those who recover graft function and survive with their original allograft. METHODS: We interrogated the United Network of Organ Sharing (UNOS) database for pediatric LT recipients who were relisted with a primary diagnosis of PNF from 2000 to 2020. Patients >21-year-old and multiple organ transplants were excluded. Logistic regression and Cox proportional hazard models were employed to identify risk factors for early re-transplantation (within 30 days of relisting) and mortality after adjusting for baseline clinical characteristics. RESULTS: One hundred and eight patients were relisted for LT for PNF during the study period. Twenty-five patients survived beyond 30 days from relisting with their original LT, 76 underwent early re-transplantation, and 7 did not survive. Having a high-risk EBV mismatch (OR 2.03, 95% CI 0.66-6.27) and an elevated donor serum creatinine (OR: 2.19, 95% CI 0.54-8.84) were associated with increased odds of a patient requiring early re-transplantation. Donor characteristics including age, final total bilirubin, final AST/ALT, and final serum sodium, as well as vasopressor use prior to procurement, were not associated with increased odds of early re-transplantation (p > 0.05). Operative characteristics including allograft type and cold-ischemia time were also not associated with early re-transplantation (p > 0.05). Patients undergoing early re-transplantation showed a trend toward improved 1-year graft survival (69% vs 55%, p = 0.24). On multivariable Cox proportional hazards modeling, early re-transplantation was associated with reduced risk of overall patient mortality compared to those who survived with their original LT (HR 0.27, 95% CI 0.12-0.67). CONCLUSION: Early re-transplantation for PNF is associated with improved patient survival compared with patients who survive with their original LT.

Estimates of number of children and adolescents without access to surgical care.

OBJECTIVE: To estimate how many children and adolescent worldwide do not have access to surgical care. METHODS: We estimated the number of children and adolescents younger than 19 years worldwide without access to safe, affordable and timely surgical care, by using population data for 2017 from the United Nations and international data on surgical access in 2015. We categorized countries by World Bank country income group and obtained the proportion of the population with no access to surgical care from a study by the Lancet Commission on Global Surgery. FINDINGS: An estimated 1.7 billion (95% credible interval: 1.6-1.8) children and adolescents worldwide did not have access to surgical care in 2017. Lack of access occurred overwhelmingly in low- and middle-income countries where children and adolescents make up a disproportionately large fraction of the population. Moreover, 453 million children younger than 5 years did not have access to basic life-saving surgical care. According to Lancet Commission on Global Surgery criteria, less than 3% of the paediatric population in low-income countries and less than 8% in lower-middle-income countries had access to surgical care. CONCLUSION: There were substantial gaps in the availability of surgical services for children worldwide, particularly in low- and middle-income countries. Future research should focus on developing specific measures for assessing paediatric surgical access, delivery and outcomes and on clarifying how limited surgical access in the poorest parts of the world affects child health, especially mortality in children younger than 5 years.

Customized Postoperative Therapy Improves Bile Drainage in Biliary Atresia: A Single Center Preliminary Report.

BACKGROUND: Controversies in management of biliary atresia (BA) after hepatoportoenterostomy (HPE) lead to variable treatment protocols. We implemented standardized medical management after HPE, customizing the use of antibiotics and corticosteroids based on patient-specific factors. METHODS: In this retrospective analysis, 20 consecutive infants underwent HPE for BA and were compared to a historical cohort. Analysis of successful biliary drainage 3 months after HPE (defined as serum total bilirubin <2 mg/dL) was the primary endpoint; survival with native liver at 2 years was the secondary endpoint. RESULTS: Sixteen of 20 (80%) infants had successful bile drainage, compared to 8 of 20 (40%) infants in the historical cohort (P = 0.0225). Sixteen of 20 patients in the new protocol have reached 2 years of age or required liver transplantation. Among the sixteen, 11 (68.8%) are alive with native livers versus 10 of 20 (50%) in the historical cohort (P = 0.0970). CONCLUSION: This preliminary report suggests the potential benefit of tailored use of postoperative antibiotics and corticosteroids in improving biliary drainage after HPE. LEVEL OF EVIDENCE: III.

Alteration of strain background and a high omega-6 fat diet induces earlier onset of pancreatic neoplasia in EL-Kras transgenic mice.

Diets containing omega-6 (ω-6) fat have been associated with increased tumor development in carcinogen-induced pancreatic cancer models. However, the effects of ω-6 fatty acids and background strain on the development of genetically-induced pancreatic neoplasia is unknown. We assessed the effects of a diet rich in ω-6 fat on the development of pancreatic neoplasia in elastase (EL)-Kras(G12D) (EL-Kras) mice in two different backgrounds. EL-Kras FVB mice were crossed to C57BL/6 (B6) mice to produce EL-Kras FVB6 F1 (or EL-Kras F1) and EL-Kras B6 congenic mice. Age-matched EL-Kras mice from each strain were compared to one another on a standard chow. Two cohorts of EL-Kras FVB and EL-Kras F1 mice were fed a 23% corn oil diet and compared to age-matched mice fed a standard chow. Pancreata were scored for incidence, frequency, and size of neoplastic lesions, and stained for the presence of mast cells to evaluate changes in the inflammatory milieu secondary to a high fat diet. EL-Kras F1 mice had increased incidence, frequency, and size of pancreatic neoplasia compared to EL-Kras FVB mice. The frequency and size of neoplastic lesions and the weight and pancreatic mast cell densities in EL-Kras F1 mice were increased in mice fed a high ω-6 fatty acid diet compared to mice fed a standard chow. We herein introduce the EL-Kras B6 mouse model which presents with increased frequency of pancreatic neoplasia compared to EL-Kras F1 mice. The phenotype in EL-Kras F1 and FVB mice is promoted by a diet rich in ω-6 fatty acid.

Carinal Resection and Reconstruction for an Obstructing Inflammatory Myofibroblastic Tumor in a Child.

Inflammatory myofibroblastic tumor (IMT) is a rare soft tissue tumor characterized by proliferation of fibroblastic cells associated with an inflammatory infiltrate. Inflammatory myofibroblastic tumors have a predilection for the pediatric population and are usually found in the lung parenchyma but rarely at the carina. They rarely metastasize but can be locally destructive. Surgical resection is the cornerstone of therapy, which results in excellent survival despite risk of local recurrence. We present the case of a nine-year-old girl with an IMT mass at the carina and obstructing the left main stem bronchus, requiring extensive resection and reconstruction.

A comparison of surgical complications after appendicostomy and neoappendicostomy in pediatric patients.

PURPOSE: There are limited data on neoappendicostomy complications owing to small patient populations. This study compares appendicostomy and neoappendicostomy procedures with an emphasis on major postoperative complications requiring either a surgical or interventional radiology procedure. METHOD: A single-institution retrospective review included all patients with complete medical charts in the Cincinnati Children's Colorectal Database who underwent either an appendicostomy or neoappendicostomy from August 2005 through December 2016. Demographics, details of the procedure, and major postoperative complications were evaluated. RESULTS: 261 patients (appendicostomy n = 208, neoappendicostomy n = 53) with a median follow up time of 2.5 years resulted in 84 patients (appendicostomy n = 60, neoappendicostomy n = 24) experiencing a total of 118 complications requiring surgical or radiologic intervention with a significant difference between the groups (29% vs 45%, RR = 1.79 (95% CI: 1.24-2.60), p < 0.01). Skin level stricture was the most common complication (20% appendicostomies vs 30% neoappendicostomies, p = 0.13). CONCLUSIONS: Appendicostomies and neoappendicostomies can be an effective way to manage fecal incontinence; however, 32% of our patients experienced a complication that required either a surgical or interventional radiology procedure. Patients need to be informed of the possible complications that are associated with appendicostomy and neoappendicostomy construction. TYPE OF STUDY: Single institution retrospective review. LEVEL OF EVIDENCE: IV.

Omega-3 Fatty Acids Prevent Early Pancreatic Carcinogenesis via Repression of the AKT Pathway.

Pancreatic cancer remains a daunting foe despite a vast number of accumulating molecular analyses regarding the mutation and expression status of a variety of genes. Indeed, most pancreatic cancer cases uniformly present with a mutation in the KRAS allele leading to enhanced RAS activation. Yet our understanding of the many epigenetic/environmental factors contributing to disease incidence and progression is waning. Epidemiologic data suggest that diet may be a key factor in pancreatic cancer development and potentially a means of chemoprevention at earlier stages. While diets high in ω3 fatty acids are typically associated with tumor suppression, diets high in ω6 fatty acids have been linked to increased tumor development. Thus, to better understand the contribution of these polyunsaturated fatty acids to pancreatic carcinogenesis, we modeled early stage disease by targeting mutant KRAS to the exocrine pancreas and administered diets rich in these fatty acids to assess tumor formation and altered cell-signaling pathways. We discovered that, consistent with previous reports, the ω3-enriched diet led to reduced lesion penetrance via repression of proliferation associated with reduced phosphorylated AKT (pAKT), whereas the ω6-enriched diet accelerated tumor formation. These data provide a plausible mechanism underlying previously observed effects of fatty acids and suggest that administration of ω3 fatty acids can reduce the pro-survival, pro-growth functions of pAKT. Indeed, counseling subjects at risk to increase their intake of foods containing higher amounts of ω3 fatty acids could aid in the prevention of pancreatic cancer.

Borderline resectable pancreatic cancer.

Borderline resectable pancreatic cancer (BRPC) is an evolving diagnostic entity that blurs the distinction between resectable and locally advanced pancreatic cancer (Varadhachary et al. Ann Surg Oncol 13:1035-1046, 2006). Until recently the management of this disease has been poorly defined; however, consensus guidelines have been developed regarding the proper management of this diagnostic entity. Recent studies have shown that if appropriately identified and treated, this subset of disease can have outcomes similar to pancreatic cancer that is defined as resectable (Laurence et al. J Gastrointest Surg 15:2059-2069, 2011). The aim of this review is to outline the current consensus on definitions, workup and management of BRPC, and also provide a summary of issues that require progress as defined by the International Study Group of Pancreatic Surgery (ISGPS).