Reduction of Pediatric Gastrostomy Tube Healthcare Utilization and Socioeconomic Disparities: Longitudinal Benefits of Quality Improvement.

BACKGROUND: Disparities in emergency department (ED) utilization after gastrostomy (G-) tube placement were previously demonstrated at our children's hospital. We aimed to reduce postoperative G-tube dislodgements and ED visits with a particular focus on socially vulnerable children. METHODS: Our improvement team implemented a G-tube care bundle (6/2018-9/2019) targeting caregiver preparedness and standardizing care in the pre-, intra-, and post-operative periods. Patients who had G tubes placed between 1/2011-8/2022 were categorized to either pre- or post-intervention groups. Primary outcomes were tracked prospectively. National area deprivation index (ADI) was assigned retrospectively and employed to evaluate social risk. Univariate comparisons were made between pre- and post-intervention groups, and between High ADI (≥80) and Low ADI (<80) subgroups in both pre- and post- intervention periods. We used statistical process control methods to further analyze change over time. RESULTS: 396 children were included (188 pre-intervention, 208 post-intervention). The post-intervention cohort demonstrated a lower rate of outpatient dislodgement at 90 days following G-tube placement (21.3 % vs 10.1 %, p = 0.002) and fewer G-tube-related ED visits per G-tube placed within one year of placement (mean 0.8 visits vs 0.6 visits, p = 0.012). Pre-intervention, children from high ADI neighborhoods had significantly greater healthcare utilization compared to those from lower ADI neighborhoods. Post-intervention, previously statistically significant disparities were no longer present. Outpatient G-tube dislodgements within 90 days were particularly mitigated. CONCLUSIONS: A longstanding quality improvement initiative has led to sustained reductions in overall G-tube-related health care utilization. Care standardization and improvement may mitigate outcome disparities related to socioeconomic advantage. TYPE OF STUDY: Retrospective Comparative Study and Prospective Quality Improvement. LEVEL OF EVIDENCE: Level III.

The Rochester Protocol for Living Donor Liver Transplantation of Unresectable Colorectal Liver Metastasis: A 5-Year Report on Selection, Approval, and Outcomes.

Living donor liver transplantation (LDLT) is a treatment option for select patients with unresectable colorectal liver metastasis (uCRLM). We describe our center's experience of patient selection, insurance approval, and outcomes after LDLT after first referral in March 2019. Of the 206 evaluated patients, twenty-three underwent LDLT. We found that patients who were referred earlier in their oncologic course were more likely to be eligible for transplantation. After completion of the Rochester Protocol for LDLT eligibility, recipients had a median delay of care of 10 days (IQR 0-36) related to insurance appeal, with six patients (30%) having a delay longer than 30 days. LDLT recipients had an overall survival proportion of 100% and 91% at 1, and 3 years; and a recurrence-free survival proportion of 100% and 40%, at 1 and 3 years, respectively. All donors underwent right hepatectomy, of which only one donor had a Clavien-Dindo IIIa complication and readmission. There was no donor mortality. We assert that multidisciplinary care and strict patient selection through the Rochester Protocol were paramount to our center's success. In the appropriately selected patient, LDLT for uCRLM may be justified, and patients should be referred to transplant oncology centers for evaluation.

Pan-lysyl oxidase inhibition disrupts fibroinflammatory tumor stroma, rendering cholangiocarcinoma susceptible to chemotherapy.

BACKGROUND: Cholangiocarcinoma (CCA) features highly desmoplastic stroma that promotes structural and functional resistance to therapy. Lysyl oxidases (LOX, LOXL1-4) catalyze collagen cross-linking, thereby increasing stromal rigidity and facilitating therapeutic resistance. Here, we evaluate the role of lysyl oxidases in stromal desmoplasia and the effects of pan-lysyl oxidase (pan-LOX) inhibition in CCA. METHODS: Resected CCA and normal liver specimens were analyzed from archival tissues. Spontaneous and orthotopic murine models of intrahepatic CCA (iCCA) were used to assess the impact of the pan-LOX inhibitor PXS-5505 in treatment and correlative studies. The functional role of pan-LOX inhibition was interrogated through in vivo and ex vivo assays. RESULTS: All 5 lysyl oxidases are upregulated in CCA and reduced lysyl oxidase expression is correlated with an improved prognosis in resected patients with CCA. Spontaneous and orthotopic murine models of intrahepatic cholangiocarcinoma upregulate all 5 lysyl oxidase isoforms. Pan-LOX inhibition reversed mechanical compression of tumor vasculature, resulting in improved chemotherapeutic penetrance and cytotoxic efficacy. The combination of chemotherapy with pan-LOX inhibition increased damage-associated molecular pattern release, which was associated with improved antitumor T-cell responses. Pan-LOX inhibition downregulated macrophage invasive signatures in vitro, rendering tumor-associated macrophages more susceptible to chemotherapy. Mice bearing orthotopic and spontaneously occurring intrahepatic cholangiocarcinoma tumors exhibited delayed tumor growth and improved survival following a combination of pan-LOX inhibition with chemotherapy. CONCLUSIONS: CCA upregulates all 5 lysyl oxidase isoforms, and pan-LOX inhibition reverses tumor-induced mechanical forces associated with chemotherapy resistance to improve chemotherapeutic efficacy and reprogram antitumor immune responses. Thus, combination therapy with pan-LOX inhibition represents an innovative therapeutic strategy in CCA.

Progression-Free Survival for Liver Transplant vs Alternative Therapy in Unresectable Colorectal Liver Metastasis.

This cohort study compares survival outcomes between patients with unresectable colorectal liver metastasis who received chemotherapy-based multimodal therapy and patients who underwent liver transplant.

High Area Deprivation Index is Associated With Discharge to Foster Care in Pediatric Patients With Non-accidental Trauma.

BACKGROUND: Outcomes after non-accidental trauma (NAT) have been shown to be impacted by social determinants of health. Our study aims to investigate the association between NAT, patient demographics, neighborhood disadvantage as measured by the Area Deprivation Index (ADI), and patient disposition. METHODS: An 8-year retrospective chart review was conducted in pediatric patients presenting to our level I trauma center with suspected NAT. Patient demographics, ADI, injury severity score (ISS), Glasgow coma scale (GCS), length of stay, and discharge disposition were analyzed using univariate and multivariate techniques to evaluate associations between patient demographics, injury severity, and patient outcomes. RESULTS: A total of 84 patients were admitted with suspected NAT. Of our study population, 45% of patients were White and 26% were Black. Black children were overrepresented in this cohort compared to general population means, while White children were underrepresented (p < 0.05). Median ADI was 6.5 (IQR 4.0-8.0). Of our cohort, 65 patients were discharged home, and 18 patients to foster care. One patient in our cohort died. An ADI >6 was the only factor significantly associated with discharge to foster care. This association held on both univariate (OR 1.4; 95% CI 1.07-1.84, p = 0.02) and multivariate (OR 1.4; 95% CI 1.05-1.86, p = 0.02) analyses. CONCLUSION: Our study found that neighborhood disadvantage, as measured by ADI, is an independent predictor of discharge to foster care. Additionally, Black children remain over-represented in the NAT population referred to our institution, including those discharged to foster care. Efforts to address healthcare disparities and community-based NAT prevention and reunification programs are necessary. TYPE OF STUDY: Prognosis Study (Retrospective Case-Control Study). LEVEL OF EVIDENCE: Level III.

Transplantation in the Pandemic Era: Perspectives on the Utilization of COVID-19 Positive Organs.

BACKGROUND: At early stages of the pandemic, most organ procurements organizations considered COVID-19 infected donors to be ineligible for organ donation. The aim of this survey is to describe the current practices of the utilization of COVID-19 positive organs donors among American Society of Transplant Surgeons (ASTS) members. METHODS: An anonymous 40-question redcap survey was emailed to ASTS members from June to August 2022. RESULTS: One hundred forty-nine surveys from 10 countries were included for analysis. The majority of the responders were men (66.7%) from North America (95%) and identified as transplant surgeons (68.5%). Most work at academic institutions (76.5%). Almost all responders (94%) were willing to accept an organ from a donor with a history of COVID-19 who tested negative at the time of donation, however, there was no consensus on the length of time after the disease was resolved. Approximately 70% indicated they accept organs from asymptomatic donors with active disease. Only 32 responders indicated they would accept an organ from an individual with a history of "severe" COVID-19 infection and less than one third of the responders would accept an organ from a donor who died from COVID-19 infection. Interestingly, 80% indicated they have protocols at their institution to guide the acceptance of such organs. DISCUSSION: Despite new evidence that the transmission of COVID-19 in non-lung organs is extremely rare, the results of this survey suggest significant heterogeneity in practice and perceptions of the use of COVID-19 positive organs across international centers. We suggest that the implementation of a standardized protocol is of paramount importance to continue safe transplant activity.

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 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.

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.

Outcomes after Child Physical Abuse and Association with Community-Level Social Determinants of Health.

BACKGROUND: Child physical abuse is a significant cause of pediatric injury and death. Previous studies have described disparities in outcomes for physically abused children according to insurance status. We hypothesized that children treated for physical abuse would be more likely to live in neighborhoods with increased socioeconomic deprivation. STUDY DESIGN: We performed a retrospective review of children who were admitted with suspected physical abuse from 2011 to 2021. Home addresses at the time of admission were used to assign an Area Deprivation Index (ADI) of the neighborhood. Clinicopathologic and outcome variables were compared between children from neighborhoods in the top 10th and bottom 90th national neighborhood ADI percentile. Univariate and multivariate logistic models were constructed. RESULTS: One hundred eighty-four children were included for analysis. Children from the top 10th (more impoverished) ADI percentile presented with more severe injuries, had higher area injury scores in the abdomen and extremities, and required admission to the intensive care unit more often, compared with children from the bottom 90th ADI percentile (all p Values <0.05). Children from high ADI neighborhoods were more likely to be discharged to a different caretaker than children from low ADI neighborhoods (71% caretaker change vs 49% caretaker change, p = 0.005). Univariate and multivariate logistic regression demonstrated statistically significant association between the ADI score and the need for caretaker change at the time of discharge (p = 0.004). CONCLUSIONS: Community-level social determinants of health are closely associated with child physical abuse. Child abuse reduction strategies might consider increased support for families with fewer resources and social support systems.

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.

What is the optimal prophylaxis against postoperative deep vein thrombosis in the living donor to avoid complications and enhance recovery? - A systematic review of the literature and expert panel recommendations.

BACKGROUND: Deep venous thrombosis (DVT) prophylaxis is often employed to prevent the potentially serious complication of pulmonary embolism (PE). However, little data exist regarding the optimal DVT prophylaxis strategy for living donors undergoing hepatectomy for living donor liver transplantation. Here we present our consensus statement on DVT prophylaxis for living donors undergoing hepatectomy. OBJECTIVES: To identify the optimal DVT prophylaxis strategy, which reduces, risk of complications in living liver donors, and enhances recovery. METHODS: Systematic review following PRISMA guidelines and recommendations using the GRADE approach derived from an international expert panel. Of interest was the impact of DVT prophylaxis or lack of prophylaxis on living donors undergoing hepatectomy and subsequent rates of DVT, PE, and hemorrhagic complications. PROSPERO ID: CRD42021260720 RESULTS: The review of the literature identified three studies, which directly addressed thrombogenesis following living donor hepatectomy. All studies were observational in nature without randomization into treatments. The rate of DVT-PE in unscreened living donors with chemoprophylaxis was 5%. Furthermore, thromboelastography of living donors demonstrated sustained hypercoagulability for 50% of donors 10 days postoperatively. In line with CHEST (The American College of Chest Physicians) guidelines of chemoprophylaxis for surgical procedures with 3% or greater risk of DVT-PE, we conclude that a minimum of 10 days of postoperative chemoprophylaxis with unfractionated heparin or low-molecular weight heparin is recommended for patients undergoing living donor hepatectomy. The quality of evidence (QOE) for these recommendations based on the GRADE criteria is low, with a Grade of Recommendation of Strong. CONCLUSIONS: Chemoprophylaxis for DVT following living donor hepatectomy is associated with reduced adverse thrombotic events, (Quality of Evidence; Low | Grade of Recommendation; Strong).