Smad4 restricts injury-provoked biliary proliferation and carcinogenesis.

Cholangiocarcinoma (CCA) is a deadly and heterogeneous type of cancer characterized by a spectrum of epidemiologic associations as well as genetic and epigenetic alterations. We seek to understand how these features inter-relate in the earliest phase of cancer development and through the course of disease progression. For this, we studied murine models of liver injury integrating the most commonly occurring gene mutations of CCA - including Kras, Tp53, Arid1a and Smad4 - as well as murine hepatobiliary cancer models and derived primary cell lines based on these mutations. Among commonly mutated genes in CCA, we found that Smad4 functions uniquely to restrict reactive cholangiocyte expansion to liver injury through restraint of the proliferative response. Inactivation of Smad4 accelerates carcinogenesis, provoking pre-neoplastic biliary lesions and CCA development in an injury setting. Expression analyses of Smad4-perturbed reactive cholangiocytes and CCA lines demonstrated shared enriched pathways, including cell-cycle regulation, MYC signaling and oxidative phosphorylation, suggesting that Smad4 may act via these mechanisms to regulate cholangiocyte proliferation and progression to CCA. Overall, we showed that TGFß/SMAD4 signaling serves as a critical barrier restraining cholangiocyte expansion and malignant transformation in states of biliary injury.

Comparable and Complimentary Modalities for Treatment of Small-Sized HCC: Surgical Resection, Radiofrequency Ablation, and Microwave Ablation.

BACKGROUND: Over the past decade, there has been continual improvement in both ablative and surgical technologies for the treatment of hepatocellular carcinoma (HCC). The efficacy of ablative therapy compared to surgical resection for HCC has not been thoroughly evaluated using multiple large-scale randomized controlled trials. By international consensus, if a patient is eligible, surgery is the primary curative treatment option, as it is believed to confer superior oncologic control. OBJECTIVE: to determine the efficacies of percutaneous ablative therapies and surgical resection (SR) in the treatment of HCC. Data sources, study appraisal, and synthesis methods: A meta-analysis using 5 online databases dating back to 1989 with more than 31,000 patients analyzing patient and tumor characteristics, median follow-up, overall survival, and complication rate was performed. RESULTS: Ablative therapies are suitable alternatives to surgical resection in terms of survival and complication rates for comparable patient populations. For the entire length of the study from 1989-2019, radiofrequency ablation (RFA) produced the highest 5-year survival rates (59.6%), followed by microwave ablation (MWA) (50.7%) and surgical resection (SR) (49.9%). In the most recent era from 2006 to 2019, surgical resection has produced the highest 5-year survival rate of 72.8%, followed by RFA at 61.7% and MWA at 50.6%. Conclusions and key findings: Depending on the disease state and comorbidities of the patient, one modality may offer superior overall survival rates over the other available techniques. Interventional ablative methods and surgical resection should be used in conjunction for the successful treatment of small-sized HCC.

Novel Benchmark Values for Open Major Anatomic Liver Resection in Non-cirrhotic Patients: A Multicentric Study of 44 International Expert Centers.

OBJECTIVE: This study aims at establishing benchmark values for best achievable outcomes following open major anatomic hepatectomy for liver tumors of all dignities. BACKGROUND: Outcomes after open major hepatectomies vary widely lacking reference values for comparisons among centers, indications, types of resections, and minimally invasive procedures. METHODS: A standard benchmark methodology was used covering consecutive patients, who underwent open major anatomic hepatectomy from 44 high-volume liver centers from 5 continents over a 5-year period (2016-2020). Benchmark cases were low-risk non-cirrhotic patients without significant comorbidities treated in high-volume centers (≥30 major liver resections/year). Benchmark values were set at the 75th percentile of median values of all centers. Minimum follow-up period was 1 year in each patient. RESULTS: Of 8044 patients, 2908 (36%) qualified as benchmark (low-risk) cases. Benchmark cutoffs for all indications include R0 resection ≥78%; liver failure (grade B/C) ≤10%; bile leak (grade B/C) ≤18%; complications ≥grade 3 and CCI ® ≤46% and ≤9 at 3 months, respectively. Benchmark values differed significantly between malignant and benign conditions so that reference values must be adjusted accordingly. Extended right hepatectomy (H1, 4-8 or H4-8) disclosed a higher cutoff for liver failure, while extended left (H1-5,8 or H2-5,8) were associated with higher cutoffs for bile leaks, but had superior oncologic outcomes, when compared to formal left hepatectomy (H1-4 or H2-4). The minimal follow-up for a conclusive outcome evaluation following open anatomic major resection must be 3 months. CONCLUSION: These new benchmark cutoffs for open major hepatectomy provide a powerful tool to convincingly evaluate other approaches including parenchymal-sparing procedures, laparoscopic/robotic approaches, and alternative treatments, such as ablation therapy, irradiation, or novel chemotherapy regimens.

Liver transplantation for unresectable colorectal liver metastasis.

PURPOSE OF REVIEW: To summarize the current state of liver transplantation (LT) for unresectable colorectal liver metastases (uCRLM), and to address future directions. RECENT FINDINGS: The Norwegian secondary cancer (SECA) I and SECA II studies demonstrated that after LT the 5-year survival of a highly selected group of patients with uCRLM could be as high as 60% and 83%, respectively. After long-term follow-up, the 5- and 10-year survival was shown to be 43% and 26%, respectively. Furthermore, data has accumulated in other countries and a North American study reported a 1.5-year survival of 100%. In addition, steady growth has been demonstrated in the US, with 46 patients transplanted to date and 19 centers enrolling patients for this indication. Lastly, although recurrence is almost universal in patients with a high tumor burden, it has not been an accurate surrogate for survival, reflecting the relatively indolent nature of recurrence after LT. SUMMARY: Growing evidence has shown that excellent survival and even cure can be achieved in highly selected patients with uCRLM, with survival rates far superior than in patients treated with chemotherapy. The next step is to create national registries to standardize selection criteria and establish the optimal approach and best practices for incorporating LT for uCRLM into the treatment armamentarium.

The High Incidence of Occult Carcinoma in Total Hepatectomy Specimens of Patients Treated for Unresectable Colorectal Liver Metastases With Liver Transplant.

OBJECTIVE: To describe the rate of occult carcinoma deposits in total hepatectomy specimens from patients treated with liver transplant (LT) for colorectal liver metastases (CRLM). BACKGROUND: Previous studies have shown that patients with CRLM treated with systemic therapy demonstrate a high rate of complete radiographic response or may have disappearing liver metastases. However, this does not necessarily translate into a complete pathologic response, and residual invasive cancer may be found in up to 80% of the disappearing tumors after resection. METHODS: Retrospective review of 14 patients who underwent LT for CRLM, at 2 centers. Radiographic and pathologic correlation of the number of tumors and their viability before and after LT was performed. RESULTS: The median (interquartile range) number of tumors at diagnosis was 11 (4-23). The median number of chemotherapy cycles was 24 (16-37). Hepatic artery infusion was used in 5 patients (35.7%); 6 (42.9%) underwent surgical resection, and 5 (35.7%) received locoregional therapy. The indication for LT was unresectability in 8 patients (57.1%) and liver failure secondary to oncologic treatment in the remaining 6 (42.9%). Before LT, 7 patients (50%) demonstrated fluorodeoxyglucose-avid tumors and 7 (50%) had a complete radiographic response. Histopathologically, 11 patients (78.6%) had a viable tumor. Nine (64.2%) of the 14 patients were found to have undiagnosed metastases on explant pathology, with at least 22 unaccounted viable tumors before LT. Furthermore, 4 (57.1%) of the 7 patients who demonstrated complete radiographic response harbored viable carcinoma on explant pathology. CONCLUSIONS: A complete radiographic response does not reliably predict a complete pathologic response. In patients with unresectable CRLM, total hepatectomy and LT represent a promising treatment options to prevent indolent disease progression from disappearing CRLM.

The Current State of Liver Transplantation for Colorectal Liver Metastases in the United States: A Call for Standardized Reporting.

BACKGROUND: Current success in transplant oncology for select liver tumors, such as hepatocellular carcinoma, has ignited international interest in liver transplantation (LT) as a therapeutic option for nonresectable colorectal liver metastases (CRLM). In the United States, the CRLM LT experience is limited to reports from a handful of centers. This study was designed to summarize donor, recipient, and transplant center characteristics and posttransplant outcomes for the indication of CRLM. METHODS: Adult, primary LT patients listed between December 2017 and March 2022 were identified by using United Network Organ Sharing database. LT for CRLM was identified from variables: "DIAG_OSTXT"; "DGN_OSTXT_TCR"; "DGN2_OSTXT_TCR"; and "MALIG_TY_OSTXT." RESULTS: During this study period, 64 patients were listed, and 46 received LT for CRLM in 15 centers. Of 46 patients who underwent LT for CRLM, 26 patients (56.5%) received LTs using living donor LT (LDLT), and 20 patients received LT using deceased donor (DDLT) (43.5%). The median laboratory MELD-Na score at the time of listing was statistically similar between the LDLT and DDLT groups (8 vs. 9, P = 0.14). This persisted at the time of LT (8 vs. 12, P = 0.06). The 1-, 2-, and 3-year, disease-free, survival rates were 75.1, 53.7, and 53.7%. Overall survival rates were 89.0, 60.4, and 60.4%, respectively. CONCLUSIONS: This first comprehensive U.S. analysis of LT for CRLM suggests a burgeoning interest in high-volume U.S. transplant centers. Strategies to optimize patient selection are limited by the scarce oncologic history provided in UNOS data, warranting a separate registry to study LT in CRLM.

Social Determinants of Health are Associated With Postoperative Outcomes in Children With Complicated Appendicitis.

INTRODUCTION: Socioeconomic disadvantage has been associated with increased complicated appendicitis rates. Our purpose was to analyze the complex interactions between social determinants of health (SDOH) and postoperative outcomes in pediatric appendicitis. MATERIALS AND METHODS: Children who underwent appendectomy at our institution (1/2015-12/2020) were retrospectively reviewed. We used home addresses to determine composite measures of neighborhood/area-level socioeconomic advantage (Area Deprivation Index [ADI] and Social Deprivation Index [SDI]), and other area-level indicators. We created a novel, composite outcome score computed as a weighted average of eight outcome measures. Feature selection and exploratory factor analysis were used to create a multivariate model predictive of outcomes. RESULTS: Of 1117 children with appendicitis, 20.59% had complicated (perforated) appendicitis. Factor analysis identified two multivariate latent factors; Factor 1 contained SDI, ADI, and % unemployed in the population, and Factor 2 contained % Hispanic and % foreign-born in the population. Low Factor 2 scores (communities with more Hispanic/foreign-born residents) were associated with increased length of stay, more frequent postoperative percutaneous drainage, and increased postoperative imaging. CONCLUSIONS: Interactions between SDOH and pediatric surgical care go beyond the individual patient and suggest that vulnerable populations are exposed to contextual conditions that may impact outcomes. Specifically, neighborhood-level factors, including the prevalence of Hispanic ethnicity and foreign-born individuals, are associated with outcomes in pediatric patients with complicated appendicitis. Reducing disparities in complicated appendicitis outcomes may involve addressing neighborhood-level SDOH through strategic reallocation of healthcare resources and developing targeted interventions to improve access to pediatric surgical care in underserved communities.

Inferior Survival Is Associated With Socioeconomic Deprivation in Hepatocellular Carcinoma.

INTRODUCTION: Pernicious health disparities have been reported in patients with hepatocellular carcinoma (HCC). Few tools exist to screen patients in order to facilitate educational and outreach initiatives. We hypothesize that neighborhood-level socioeconomic metrics such as the Area Deprivation Index (ADI) can predict inferior outcomes in patients with early-stage HCC. METHODS: A single institution's retrospective review of patients with Surveillance, Epidemiology, and End Results Stage I HCC between 2000 and 2020 was conducted. Univariate and multivariate models were constructed to identify clinical and socioeconomic variables correlated with treatment-specific survival. Kaplan-Meier analysis was performed to compare survival differences between cohorts. RESULTS: A total of 558 patients were included in this study with newly diagnosed Surveillance, Epidemiology, and End Results Stage I HCC. Multivariate models demonstrated native model of end-stage liver disease, largest tumor size, insurance type, the distance to our transplant center, and the ADI score, a validated metric for a patient's socioeconomic status, are independent risk factors for worse overall survival (all P-values < 0.05). Concerningly, despite similar maximal tumor size, number of tumors, and native model of end-stage liver disease scores, patients from high ADI neighborhoods are 20% less likely to receive surgical treatment, especially liver transplantation. CONCLUSIONS: The ADI is a useful tool for identifying patients at the time of presentation who are at risk for inferior treatment for early stage HCC, and the ADI should be incorporated as a social vital sign.

Recipient and Donor Outcomes After Living-Donor Liver Transplant for Unresectable Colorectal Liver Metastases.

Importance: Colorectal cancer is a leading cause of cancer-related death, and nearly 70% of patients with this cancer have unresectable colorectal cancer liver metastases (CRLMs). Compared with chemotherapy, liver transplant has been reported to improve survival in patients with CRLMs, but in North America, liver allograft shortages make the use of deceased-donor allografts for this indication problematic. Objective: To examine survival outcomes of living-donor liver transplant (LDLT) for unresectable, liver-confined CRLMs. Design, Setting, and Participants: This prospective cohort study included patients at 3 North American liver transplant centers with established LDLT programs, 2 in the US and 1 in Canada. Patients with liver-confined, unresectable CRLMs who had demonstrated sustained disease control on oncologic therapy met the inclusion criteria for LDLT. Patients included in this study underwent an LDLT between July 2017 and October 2020 and were followed up until May 1, 2021. Exposures: Living-donor liver transplant. Main Outcomes and Measures: Perioperative morbidity and mortality of treated patients and donors, assessed by univariate statistics, and 1.5-year Kaplan-Meier estimates of recurrence-free and overall survival for transplant recipients. Results: Of 91 evaluated patients, 10 (11%) underwent LDLT (6 [60%] male; median age, 45 years [range, 35-58 years]). Among the 10 living donors, 7 (70%) were male, and the median age was 40.5 years (range, 27-50 years). Kaplan-Meier estimates for recurrence-free and overall survival at 1.5 years after LDLT were 62% and 100%, respectively. Perioperative morbidity for both donors and recipients was consistent with established standards (Clavien-Dindo complications among recipients: 3 [10%] had none, 3 [30%] had grade II, and 4 [40%] had grade III; donors: 5 [50%] had none, 4 [40%] had grade I, and 1 had grade III). Conclusions and Relevance: This study's findings of recurrence-free and overall survival rates suggest that select patients with unresectable, liver-confined CRLMs may benefit from total hepatectomy and LDLT.

Early postoperative ERAS compliance predicts decreased length of stay and complications following liver resection.

BACKGROUND: Enhanced recovery after surgery (ERAS) components for liver resection lack standardization and compliance. We evaluated our ERAS protocol and describe the association of postoperative ERAS compliance with length of stay (LOS) and complications. METHODS: We retrospectively reviewed patients undergoing liver resection at our institution from 2016 to 2020. Pre- and post-ERAS outcomes and compliance at 72 h were compared with LOS and complications. LOS beyond 72 h was defined as LOS72. RESULTS: 210 patients were included. Post-ERAS patients had significantly shorter LOS (5.1 vs. 7.3 days, p = 0.0014) with no difference in 30-day mortality, morbidity, or readmissions. ERAS components associated with shorter LOS72 were regular diet (HR 1.73), fluid discontinuation (HR 1.63), drain removal (HR 1.94), multimodal and oral analgesia (HR 1.51), and ambulation >100 ft (HR 2.23). LOS72 was 1-day for ≥9 ERAS component compliance, 4-days for 6-8 components, and 6-days for <6 components. 30-day complication rates for patients with ≥9 components by postoperative day 3 (POD3) were significantly lower than those with 6-8 (12 vs 32%). CONCLUSION: ERAS decreases LOS after liver resection. Nutritional advancement, drain discontinuation, multimodal and oral analgesia, and ambulation >100 ft by POD3 are associated with decreased LOS72. Achieving ≥6 components by POD3 predicts decreased LOS72 and complications.

GM-CSF drives myelopoiesis, recruitment and polarisation of tumour-associated macrophages in cholangiocarcinoma and systemic blockade facilitates antitumour immunity.

OBJECTIVE: Intrahepatic cholangiocarcinoma (iCCA) is rising in incidence, and at present, there are limited effective systemic therapies. iCCA tumours are infiltrated by stromal cells, with high prevalence of suppressive myeloid populations including tumour-associated macrophages (TAMs) and myeloid-derived suppressor cells (MDSCs). Here, we show that tumour-derived granulocyte-macrophage colony-stimulating factor (GM-CSF) and the host bone marrow is central for monopoiesis and potentiation of TAMs, and abrogation of this signalling axis facilitates antitumour immunity in a novel model of iCCA. METHODS: Blood and tumours were analysed from iCCA patients and controls. Treatment and correlative studies were performed in mice with autochthonous and established orthotopic iCCA tumours treated with anti-GM-CSF monoclonal antibody. RESULTS: Systemic elevation in circulating myeloid cells correlates with poor prognosis in patients with iCCA, and patients who undergo resection have a worse overall survival if tumours are more infiltrated with CD68+ TAMs. Mice with spontaneous iCCA demonstrate significant elevation of monocytic myeloid cells in the tumour microenvironment and immune compartments, and tumours overexpress GM-CSF. Blockade of GM-CSF with a monoclonal antibody decreased tumour growth and spread. Mice bearing orthotopic tumours treated with anti-GM-CSF demonstrate repolarisation of immunosuppressive TAMs and MDSCs, facilitating T cell response and tumour regression. GM-CSF blockade dampened inflammatory gene networks in tumours and TAMs. Human tumours with decreased GM-CSF expression exhibit improved overall survival after resection. CONCLUSIONS: iCCA uses the GM-CSF-bone marrow axis to establish an immunosuppressive tumour microenvironment. Blockade of the GM-CSF axis promotes antitumour T cell immunity.

Picomets: Assessing single and few cell metastases in melanoma sentinel lymph node biopsies.

BACKGROUND: Lymph node involvement is a significant prognostic factor for melanoma. Both number of positive nodes and disease burden within a lymph node affects survival. However, the significance of few tumor cells within a single node and subsequent optimal management remains without consensus. We investigated the implications of minimal nodal disease on clinical outcomes. METHODS: We reviewed 752 patients who underwent lymph node sampling at time of primary melanoma resection at our institution over 15 years. We deemed patients who had 1 node with 1 to 4 atypical cells staining positive for either Melan-A or Sox-10 as having "picomets." We examined the initial clinicopathological features, subsequent management, and outcomes. RESULTS: Thirty-three patients (4%) met criteria for having picomets. The most common number of positively staining atypical cells was 1 (n = 13). Nodal staging at initial pathology review varied, and overall stage ranged from IA to IIIC. Four patients underwent further therapy, none of whom had recurrent disease. Of the 29 patients undergoing observation/surveillance only, 5 had disease recurrence (17%). CONCLUSION: Although patients with picomets had better outcomes than historical stage matched cohorts, a small subset had recurrent disease. Staging patients with picomets as "N0" may not reflect the true negative prognostic significance of picomets. A larger population of patients meeting picomets criteria is needed to draw further conclusions.

Narcotic Free Cervical Endocrine Surgery: A Shift in Paradigm.

BACKGROUND AND OBJECTIVE: The opioid epidemic has stimulated initiatives to reduce the number of unnecessary narcotic prescriptions. We adopted an opt-in prescription system for patients undergoing ambulatory cervical endocrine surgery (CES). We hypothesized that empowering patients to decide whether or not to receive narcotics for pain control would result in fewer unnecessary opioid prescriptions. METHODS: We enrolled all patients scheduled for outpatient CES between July 2017 and June 2018 in a narcotic opt-in program. Patient demographics, procedure characteristics, and postoperative pain scores were collected prospectively. Statistical analyses were performed to correlate clinical predictors with narcotic request. Results were compared against a historical control group. The study was approved by the University IRB. RESULTS: A total of 216 consecutive patients underwent outpatient CES following implementation of the program. Only nine (4%) requested prescription narcotic medication at discharge, and no patient called after discharge to request analgesic medications. Compared with our prior treatment paradigm, we achieved a 96.6% reduction in the number of narcotic tablets prescribed, and a 98% reduction in unconsumed tablets. Univariate analysis suggested history of substance abuse (P < 0.001), anxiety (P = 0.01), depression (P < 0.001), baseline narcotic use (P = 0.004), highest pain postoperatively (P = 0.004), and incision length (P = 0.007) as predictive for narcotic request. Multivariate analysis retained significance with incision length and history of substance abuse. CONCLUSION: By empowering patients undergoing ambulatory CES to accept or decline a prescription, we reduced the number of prescribed narcotic tablets by 96.6%. Although longer incisions and prior substance abuse predict higher likelihood of requesting pain medication on discharge, 207 of 216 patients were treated with acetaminophen alone.

Early Prediction of Length of Stay After Pancreaticoduodenectomy.

BACKGROUND: Enhanced recovery after surgery (ERAS) is an evidence-based clinical pathway designed to standardize and optimize care. We studied the impact of ERAS and sought to identify the most important recommendations to predict shorter length of stay (LOS) after pancreaticoduodenectomy (PD). METHODS: We retrospectively reviewed all patients undergoing PD at our institution between January 2014 and June 2018. We compared clinicopathologic outcomes for patients before and after ERAS implementation. We defined "A-recommendations" as those that were graded "strong" and had "moderate" or "high" levels of evidence. We then compared outcomes of the ERAS group with adherence to "A-recommendations" and performed a subset analysis of "A-recommendations" over the first 72 h after surgery, which we termed "early factors". RESULTS: A total of 191 patients underwent PD during the study period. We excluded 87 patients who had minimally invasive PD (22), vascular reconstruction (53), or both (12). Of the 104 patients studied, 56 (54%) were pre-ERAS and 48 (46%) were ERAS. There were no differences in comorbidities or demographics between these groups, and morbidity, mortality, and readmission rates were also similar (P > 0.6). Median LOS was 3.5 d shorter in the ERAS group (7 versus 10.5 d, P < 0.001). Adherence to "A-recommendations" within ERAS was associated with a decreased LOS (r = -0.52 P = 0.0001). Patients with >5 "early factors" had a median LOS of 6 d, whereas patients with <5 "early factors" had a median LOS of 9 d (P = 0.008). CONCLUSIONS: ERAS is an effective protocol that standardizes care and reduces LOS after PD. Implementation of ERAS resulted in a 3.5-day reduction in our LOS with no change in morbidity, mortality, or readmissions. Adherence to ERAS protocol "A-recommendations" and ≥5 "early factors" may be predictive of shortened LOS.

Implementation of a gastrostomy care bundle reduces dislodgements and length of stay.

PURPOSE: Pediatric gastrostomy tubes (G-tubes) are associated with considerable utilization of healthcare resources. G-tube dislodgement can result in tract disruption and abdominal sepsis. We aimed to reduce early G-tube dislodgement by 25%. METHODS: An interdisciplinary team convened to identify key drivers of G-tube dislodgement and implement initiatives to reduce this complication. A G-tube care bundle was implemented in 2018. Rates of early G-tube dislodgement (within 90 days of insertion) were tracked. 15 months of cases after bundle implementation were compared to 20 months of cases before implementation. Length of stay (LOS, balancing measure) and bundle compliance (process measure) were tracked. RESULTS: G-tube dislodgements decreased 47% after bundle implementation. Overall, dislodgements after G-tube insertion decreased from 43% to 19% dislodgements per tube inserted, p = 0.004. Reductions were observed for dislodgements occurring in both the inpatient (14% vs. 1.5%) and outpatient (29% vs. 18%) settings. Median LOS was reduced from 15.3 to 7.1 days following implementation, p = 0.004. Process measures demonstrated 75% or greater compliance one year after implementation. CONCLUSION: An interdisciplinary team using quality improvement science methodology can significantly reduce G-tube dislodgement and improve value after pediatric gastrostomy tube insertion. TYPE OF STUDY: Longitudinal cohort study. LEVEL OF EVIDENCE: III.

Emergency department utilization following pediatric gastrostomy tube placement is driven by a small cohort of patients.

PURPOSE: Pediatric gastrostomy tubes (G-tubes) are associated with frequent postoperative problems and consumption of healthcare resources. We hypothesized that a small cohort of patients disproportionately drives healthcare resource utilization after G-tube insertion. This study aimed to characterize this population in order to implement evidence-based pathways to reduce healthcare utilization after G-tube insertion. METHODS: All surgically placed pediatric G-tubes at a quaternary care center between March 2011 and June 2018 were retrospectively reviewed. Healthcare utilization including radiographic studies, emergency department (ED) visits, hospital admissions, procedures, and diagnoses was abstracted. Encounter specific charges based on CPT codes were collected. Statistical analyses were performed with Mann Whitney U, Fisher's Exact Test, and multivariate nominal logistic regression. Institutional review board approval was obtained. RESULTS: During the study period, 189 patients underwent G-tube insertion; 24% of patients presented to the ED two or more times and accounted for 82% of ED visits. This cohort of high ED utilizers was more likely to present with G-tube dislodgement [both within the first three months (early) and after three months (late)], required more radiographic studies, and accrued significantly more charges compared to low ED utilizers. Multivariate analyses demonstrated high ED utilization was significantly associated with non-Caucasian race and the surgeon performing the procedure. CONCLUSIONS: At our institution, a significant proportion of healthcare utilization following G-tube placement is consumed by a relatively small cohort of children. Future efforts will target patients with two or more G-tube related ED visits or an early G-tube dislodgement for additional education and integration with outpatient resources. TYPE OF STUDY: Retrospective study. LEVEL OF EVIDENCE: Level II.