Enhanced recovery after surgery (ERAS®) society guidelines for gynecologic oncology: Addressing implementation challenges - 2023 update.

BACKGROUND: Despite evidence supporting its use, many Enhanced Recovery After Surgery (ERAS) recommendations remain poorly adhered to and barriers to ERAS implementation persist. In this second updated ERAS® Society guideline, a consensus for optimal perioperative care in gynecologic oncology surgery is presented, with a specific emphasis on implementation challenges. METHODS: Based on the gaps identified by clinician stakeholder groups, nine implementation challenge topics were prioritized for review. A database search of publications using Embase and PubMed was performed (2018-2023). Studies on each topic were selected with emphasis on meta-analyses, randomized controlled trials, and large prospective cohort studies. These studies were then reviewed and graded by an international panel according to the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) system. RESULTS: All recommendations on ERAS implementation challenge topics are based on best available evidence. The level of evidence for each item is presented accordingly. CONCLUSIONS: The updated evidence base and recommendations for stakeholder derived ERAS implementation challenges in gynecologic oncology are presented by the ERAS® Society in this consensus review.

Outcomes of enhanced recovery after surgery (ERAS) in gynecologic oncology - A systematic review and meta-analysis.

OBJECTIVE: To assess the benefit of Enhanced Recovery After Surgery (ERAS) on length of stay (LOS), postoperative complications, 30-day readmission, and cost in gynecologic oncology. METHODS: A systematic literature search was performed in MEDLINE, EMBASE, Cochrane Register of Controlled Trials, and Web of Science for all peer-reviewed cohort studies and controlled trials on ERAS involving gynecologic oncology patients. Abstracts, commentaries, non-controlled studies, and studies without specific data on gynecologic oncology patients were excluded. Meta-analysis was performed on the primary endpoint of LOS. Subgroup analyses were performed based on risk of bias of the studies included, number of ERAS elements, and ERAS compliance. Secondary endpoints were readmission rate, complications, and cost. RESULTS: A total of 31 studies (6703 patients) were included: 5 randomized controlled trials, and 26 cohort studies. Meta-analysis of 27 studies (6345 patients) demonstrated a decrease in LOS of 1.6 days (95% confidence interval, CI 1.2-2.1) with ERAS implementation. Meta-analysis of 21 studies (4974 patients) demonstrated a 32% reduction in complications (OR 0.68, 95% CI 0.55-0.83) and a 20% reduction in readmission (OR 0.80, 95% CI 0.64-0.99) for ERAS patients. There was no difference in 30-day postoperative mortality (OR 0.61, 95% CI 0.23-1.6) for ERAS patients compared to controls. No difference in the odds of complications or reduction in LOS was observed based on number of included ERAS elements or reported compliance with ERAS interventions. The mean cost savings for ERAS patients was $2129 USD (95% CI $712 - $3544). CONCLUSIONS: ERAS protocols decrease LOS, complications, and cost without increasing rates of readmission or mortality in gynecologic oncology surgery. This evidence supports implementation of ERAS as standard of care in gynecologic oncology.

Patterns of genomic loss of heterozygosity predict homologous recombination repair defects in epithelial ovarian cancer.

BACKGROUND: Defects in BRCA1, BRCA2, and other members of the homologous recombination pathway have potential therapeutic relevance when used to support agents that introduce or exploit double-stranded DNA breaks. This study examines the association between homologous recombination defects and genomic patterns of loss of heterozygosity (LOH). METHODS: Ovarian tumours from two independent data sets were characterised for defects in BRCA1, BRCA2, and RAD51C, and LOH profiles were generated. Publically available data were downloaded for a third independent data set. The same analyses were performed on 57 cancer cell lines. RESULTS: Loss of heterozygosity regions of intermediate size were observed more frequently in tumours with defective BRCA1 or BRCA2 (P=10(-11)). The homologous recombination deficiency (HRD) score was defined as the number of these regions observed in a tumour sample. The association between HRD score and BRCA deficiency was validated in two independent ovarian cancer data sets (P=10(-5) and 10(-29)), and identified breast and pancreatic cell lines with BRCA defects. CONCLUSION: The HRD score appears capable of detecting homologous recombination defects regardless of aetiology or mechanism. This score could facilitate the use of PARP inhibitors and platinum in breast, ovarian, and other cancers.

The role of the polymorphonuclear leukocyte in the induction of corneal edema.

Corneal inflammation is frequently associated with the development of corneal edema. It has been suggested the development of corneal edema might in some way be related to the presence of polymorphonuclear leukocytes (PMNLs) within inflamed corneas. In the present studies, it was found that corneal thickness markedly increased after experimental infection with Pseudomonas aeruginosa, but in guinea pigs made neutropenic by whole body irradiation, significantly less of an increase in corneal thickness occurred. Furthermore, corneas from non-neutropenic animals experimentally infected with P. aeruginosa consistently showed a greater increase in water content than did infected corneas from neutropenic animals. Over the first 48 hr of infection, the increase in corneal water was directly proportional to the corneal ingress of radiolabelled PMNLs. Corneal inflammation induced by intracorneal injection of the PMNL chemotactic agents phorbol myristate acetate (PMA) or endotoxin was also associated with a significant increase in corneal water compared with neutropenic animals. These data strongly suggest that activated PMNLs in the cornea are responsible for the induction of corneal edema in infected corneas.

Corneal endothelial morphology in the rat. Effects of aging, diabetes, and topical aldose reductase inhibitor treatment.

Increases in corneal endothelial cell polymegathism and pleomorphism are characteristic of diabetic human and dog corneas. This study investigated the rat as a model for age- and diabetes-related changes in endothelial cell morphology. As in most mammals, aging of the normal rat results in a progressive decrease in cell density as well as reduced numbers of hexagonal endothelial cells and increased coefficient of variation of cell size after age 34 weeks. Streptozotocin-induced diabetes produced an early progressive increase in the coefficient of variation of cell size and decrease in percentage of hexagonal cells so that diabetic rats were significantly different from age-matched normal rats by 24 weeks of age. Topical treatment with the aldose reductase inhibitor, AL 1576, begun immediately after diabetes induction, prevents endothelial cell changes and cataract formation. Topical aldose reductase inhibition also reverses endothelial cell changes when treatment is begun 8 weeks after streptozotocin injection. These results indicate that the rat is a good model for studying diabetes-induced corneal endothelial changes and that topical aldose reductase inhibitors may be effective in preventing or reversing diabetic corneal endothelial cell changes.

Correlation of corneal endothelial pump site density, barrier function, and morphology in wound repair.

After transcorneal freezing, physiologic function (pump and barrier) of the regenerating rabbit corneal endothelium was evaluated and compared with the morphologic differentiation that occurs during wound healing. Endothelial pump function was investigated utilizing the specific binding of tritiated ouabain to endothelial Na+/K+ ATPase (pump sites); the permeabilities of isolated de-epithelialized corneas to labeled inulin and dextran were measured to determine endothelial barrier function. Endothelial recovery after transcorneal freezing can be described as a three-stage process. Stage one is characterized by the establishment of an initial coverage of the wound by pleomorphic spindle-shaped cells which form a functional but incomplete barrier and minimal pump site density. In stage two, the cells assume a flattened configuration consisting of irregular polygons and establish nearly normal pump capacity. In stage three, a significant remodeling of the monolayer continues despite the layer's early physiologic recovery.

Copper transport and metabolism are normal in aceruloplasminemic mice.

Ceruloplasmin is an abundant serum glycoprotein containing greater than 95% of the copper found in the plasma of vertebrate species. Although this protein is known to function as an essential ferroxidase, the role of ceruloplasmin in copper transport and metabolism remains unclear. To elucidate the role of ceruloplasmin in copper metabolism, the kinetics of copper absorption, transport, distribution, and excretion were examined utilizing (64)Cu in wild-type and aceruloplasminemic mice. No differences in gastrointestinal absorption, hepatic uptake, or biliary excretion were observed in these animals. Furthermore, steady state measurements of tissue copper content utilizing (64)Cu and atomic absorption spectroscopy revealed no differences in the copper content of the brain, heart, spleen, and kidney. Consistent with these findings, the activity of copper-zinc superoxide dismutase in these tissues was equivalent in wild-type and ceruloplasmin-deficient mice. Hepatic iron was elevated 3.5-fold in aceruloplasminemic mice because of the loss of ferroxidase function. Hepatic copper content was markedly increased in aceruloplasminemic mice. As no differences were observed in copper absorption or biliary copper excretion, these data suggest that in these animals, hepatocyte copper intended for ceruloplasmin incorporation is trafficked into a compartment that is less available for biliary copper excretion. Taken together, these data reveal no essential role for ceruloplasmin in copper metabolism and suggest a previously unappreciated complexity to the subcellular distribution of this metal within the hepatocyte secretory pathway.