Improved Postoperative Pain Management Outcomes After Implementation of Enhanced Recovery After Surgery (ERAS) Protocol for Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy (CRS-HIPEC).

BACKGROUND: Cytoreductive surgery with hyperthermic intraperitoneal chemotherapy (CRS-HIPEC) for patients with peritoneal carcinomatosis is promising but has potential for significant morbidity and prolonged hospitalization. Enhanced Recovery After Surgery (ERAS) is a standardized protocol designed to optimize perioperative care. This study describes trends in epidural and opioid use after implementing ERAS for CRS-HIPEC at a tertiary academic center. METHODS: A retrospective analysis of patients undergoing CRS-HIPEC from January 2020 to September 2023 was conducted. ERAS was implemented in February 2022. Medication and outcomes data were compared before and after ERAS initiation. All opioids were converted to morphine milligram equivalents (MMEs). RESULTS: A total of 136 patients underwent CRS-HIPEC: 73 (54%) pre- and 63 (46%) post-ERAS. Epidural usage increased from 63% pre-ERAS to 87% post-ERAS (p = 0.001). Compared with those without epidurals, patients with epidurals had decreased total 7-day oral and intravenous (IV) opioid requirements (45 MME vs. 316 MME; p < 0.001). There was no difference in 7-day opioid totals between pre- and post-ERAS groups. After ERAS, more patients achieved early ambulation (83% vs. 53%; p < 0.001), early diet initiation (81% vs. 25%; p < 0.001), and early return of bowel function (86% vs. 67%; p = 0.012). CONCLUSIONS: ERAS implementation for CRS-HIPEC was associated with increased epidural use, decreased oral and IV opioid use, and earlier bowel function return. Our study demonstrates that epidural analgesia provides adequate pain control while significantly decreasing oral and IV opioid use, which may promote gastrointestinal recovery postoperatively. These findings support the implementation of an ERAS protocol for effective pain management in patients undergoing CRS-HIPEC.

Impact of Successful Implementation of an Enhanced Recovery After Surgery Protocol for Patients Undergoing Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy.

BACKGROUND: Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS/HIPEC) are complex operations for the treatment of peritoneal metastases. Enhanced recovery after surgery (ERAS) protocols are intended to standardize preoperative, intraoperative, and postoperative pathways, with the goal of improving patient care. This study describes feasibility and outcomes after implementing an ERAS protocol for CRS/HIPEC at a tertiary academic center. METHODS: A single-institution experience of CRS/HIPEC was reviewed from January 2020 to March 2023. Patients were categorized according to whether they underwent CRS/HIPEC before or after ERAS initiation. Outcomes and protocol adherence were evaluated. RESULTS: A total of 115 CRS/HIPEC operations were included-74 before and 41 after ERAS implementation. Median age was younger in the post-ERAS group, whereas sex, comorbidities, peritoneal carcinomatosis index, operation performed, and operative time were similar between groups. The most common primary cancer sites were gynecologic (40%), appendiceal (24%), and colorectal (22%). Adherence to all postoperative ERAS components was 76%. More post-ERAS patients ambulated by postoperative day (POD) 1 (90% vs. 54%; p < 0.001), tolerated liquid diet by POD 2 (88% vs. 32%; p < 0.001), and had foley removed by POD 3 (86% vs. 43%; p < 0.001). There was a trend toward decreased length of stay in the post-ERAS cohort (7 vs. 8 days; p = 0.092), with no difference in major complications, intensive care unit admission, or 30-day readmission. CONCLUSIONS: Despite the heterogeneity of CRS/HIPEC operations, implementing an ERAS protocol for our patients was feasible and resulted in postoperative outcomes and adherence comparable with that of other major abdominal surgeries. This supports the potential for success in ERAS programs for CRS/HIPEC patients.

Factors Predicting Readmission and Mortality in Patients Admitted for Malignant Bowel Obstruction.

INTRODUCTION: Malignant bowel obstruction (MBO) is a common complication of patients with advanced malignancies and has poor prognosis. Currently, there are limited guidelines for MBO management or predicting outcomes for these patients. OBJECTIVE: To identify patient factors associated with readmission and mortality after hospital admission for MBO. PARTICIPANTS: A 5-year retrospective review was performed from 2017 to 2022 at a single tertiary institution to evaluate patients admitted for MBO. All patients had advanced cancer of gastrointestinal or gynecologic primary. Patient demographics, socioeconomic factors, tumor characteristics, and inpatient outcomes were collected. Multivariable analyses were performed to determine variables predicting hospital readmission for recurrent MBO and 90-day mortality. RESULTS: 210 patients were included. Mean age was 61 years, 28% were male, and 19% did not primarily speak English. 35% of patients lived over 50 miles from the hospital. On multivariable analysis, non-English speaking patients exhibited increased risk of readmission for MBO (OR = 2.82, P = .039). Older age was associated with decreased risk for MBO readmission (OR = .96, P = .007). Ascites was associated with increased mortality (OR = 2.17, P = .043). Earlier palliative care (PC) consultation predicted decreased readmission (OR = .24, P < .001) yet increased mortality at 90 days (OR = 3.20, P = .003). CONCLUSION: Patient age, primary language, and PC consult were predictors for MBO readmission, which may impact 90-day mortality. Given the palliative nature of MBO, modifiable factors such as PC consultation and multidisciplinary goals of care discussions should be prioritized in order to reduce readmissions and focus on quality of life (QOL) for this patient population.

Dysregulated Repeat Element Viral-like Immune Response in Hepatocellular Carcinoma.

Purpose: Dysregulation of viral-like repeat RNAs are a common feature across many malignancies that are linked with immunological response, but the characterization of these in hepatocellular carcinoma (HCC) is understudied. In this study, we performed RNA in situ hybridization (RNA-ISH) of different repeat RNAs, immunohistochemistry (IHC) for immune cell subpopulations, and spatial transcriptomics to understand the relationship of HCC repeat expression, immune response, and clinical outcomes. Experimental Design: RNA-ISH for LINE1, HERV-K, HERV-H, and HSATII repeats and IHC for T-cell, Treg, B-cell, macrophage, and immune checkpoint markers were performed on 43 resected HCC specimens. Spatial transcriptomics on tumor and vessel regions of interest was performed on 28 specimens from the same cohort. Results: High HERV-K and high LINE1 expression were both associated with worse overall survival. There was a positive correlation between LINE1 expression and FOXP3 T-regulatory cells (r = 0.51 p < 0.001) as well as expression of the TIM3 immune checkpoint (r = 0.34, p = 0.03). Spatial transcriptomic profiling of HERV-K high and LINE-1 high tumors identified elevated expression of multiple genes previously associated with epithelial mesenchymal transition, cellular proliferation, and worse overall prognosis in HCC including SSX1, MAGEC2, and SPINK1. Conclusion: Repeat RNAs may serve as useful prognostic biomarkers in HCC and may also serve as novel therapeutic targets. Additional study is needed to understand the mechanisms by which repeat RNAs impact HCC tumorigenesis.

Reverse Transcriptase Inhibition Disrupts Repeat Element Life Cycle in Colorectal Cancer.

Altered RNA expression of repetitive sequences and retrotransposition are frequently seen in colorectal cancer, implicating a functional importance of repeat activity in cancer progression. We show the nucleoside reverse transcriptase inhibitor 3TC targets activities of these repeat elements in colorectal cancer preclinical models with a preferential effect in p53-mutant cell lines linked with direct binding of p53 to repeat elements. We translate these findings to a human phase II trial of single-agent 3TC treatment in metastatic colorectal cancer with demonstration of clinical benefit in 9 of 32 patients. Analysis of 3TC effects on colorectal cancer tumorspheres demonstrates accumulation of immunogenic RNA:DNA hybrids linked with induction of interferon response genes and DNA damage response. Epigenetic and DNA-damaging agents induce repeat RNAs and have enhanced cytotoxicity with 3TC. These findings identify a vulnerability in colorectal cancer by targeting the viral mimicry of repeat elements. SIGNIFICANCE: Colorectal cancers express abundant repeat elements that have a viral-like life cycle that can be therapeutically targeted with nucleoside reverse transcriptase inhibitors (NRTI) commonly used for viral diseases. NRTIs induce DNA damage and interferon response that provide a new anticancer therapeutic strategy. This article is highlighted in the In This Issue feature, p. 1397.