The KORE-INNOVATION trial, a prospective controlled multi-site clinical study to implement and assess the effects of an innovative peri-operative care pathway for patients with ovarian cancer: rationale, methods and trial design.

BACKGROUND: Advanced ovarian cancer is managed by extensive surgery, which could be associated with high morbidity. A personalized pre-habilitation strategy combined with an 'enhanced recovery after surgery' (ERAS) pathway may decrease post-operative morbidity. PRIMARY OBJECTIVE: To analyze the effects of a combined multi-modal pre-habilitation and ERAS strategy on severe post-operative morbidity for patients with ovarian cancer (primary diagnosis or first recurrence) undergoing cytoreductive surgery. STUDY HYPOTHESIS: A personalized multi-modal pre-habilitation algorithm entailing a physical fitness intervention, nutritional and psycho-oncological support, completed by an ERAS pathway, reduces post-operative morbidity. TRIAL DESIGN: This is a prospective, controlled, non-randomized, open, interventional two-center clinical study. Endpoints will be compared with a three-fold control: (a) historic control group (data from institutional ovarian cancer databases); (b) prospective control group (assessed before implementing the intervention); and (c) matched health insurance controls. INCLUSION CRITERIA: Patients with ovarian, fallopian, or primary peritoneal cancer undergoing primary surgical treatment (primary ovarian cancer or first recurrence) can be included. The intervention group receives an additional multi-level study treatment: (1) standardized frailty assessment followed by (2) a personalized tri-modal pre-habilitation program and (3) peri-operative care according to an ERAS pathway. EXCLUSION CRITERIA: Inoperable disease or neoadjuvant chemotherapy, simultaneous diagnosis of simultaneous primary tumors, in case of interference with the overall prognosis (except for breast cancer); dementia or other conditions that impair compliance or prognosis. PRIMARY ENDPOINT: Reduction of severe post-operative complications (according to Clavien- Dindo Classification (CDC) III-V) within 30 days after surgery. SAMPLE SIZE: Intervention group (n=414, of which approximately 20% insure with the participating health insurance); historic control group (n=198); prospective control group (n=50), health insurance controls (for those intervention patients who are members of the participating health insurance). ESTIMATED DATES FOR COMPLETING ACCRUAL AND PRESENTING RESULTS: The intervention phase started in December 2021 and will continue until June 2023. As of March 2023, 280 patients have been enrolled in the intervention group. The expected completion of the entire study is September 2024. TRIAL REGISTRATION: NCT05256576.

Placenta Accreta Spectrum Part I: anesthesia considerations based on an extended review of the literature.

"Placenta Accreta Spectrum" (PAS) describes abnormal placental adherence to the uterine wall without spontaneous separation at delivery. Though relatively rare, PAS presents a particular challenge to anesthesiologists, as it is associated with massive peripartum hemorrhage and high maternal morbidity and mortality. Standardized evidence-based PAS management strategies are currently evolving and emphasize: "PAS centers of excellence", multidisciplinary teams, novel diagnostics/pharmaceuticals (especially regarding hemostasis, hemostatic agents, point-of-care diagnostics), and novel operative/interventional approaches (expectant management, balloon occlusion, embolization). Though available data are heterogeneous, these developments affect anesthetic management and must be considered in planed anesthetic approaches. This two-part review provides a critical overview of the current evidence and offers structured evidence-based recommendations to help anesthesiologists improve outcomes for women with PAS. This first part discusses PAS management in centers of excellence, multidisciplinary care team, anesthetic approach and monitoring, surgical approaches, patient safety checklists, temperature management, interventional radiology, postoperative care and pain therapy. The diagnosis and treatment of hemostatic disturbances and preoperative prepartum anemia, blood loss, transfusion management and postpartum venous thromboembolism will be addressed in the second part of this series.

Placenta Accreta Spectrum Part II: hemostatic considerations based on an extended review of the literature.

"Placenta Accreta Spectrum" (PAS) is a rare but serious pregnancy condition where the placenta abnormally adheres to the uterine wall and fails to spontaneously release after delivery. When it occurs, PAS is associated with high maternal morbidity and mortality - as PAS management can be particularly challenging. This two-part review summarizes current evidence in PAS management, identifies its most challenging aspects, and offers evidence-based recommendations to improve management strategies and PAS outcomes. The first part of this two-part review highlighted the general anesthetic approach, surgical and interventional management strategies, specialized "centers of excellence," and multidisciplinary PAS treatment teams. The high rates of PAS morbidity and mortality are often provoked by PAS-associated coagulopathies and peripartal hemorrhage (PPH). Anesthesiologists need to be prepared for massive blood loss, transfusion, and to manage potential coagulopathies. In this second part of this two-part review, we specifically reviewed the current literature pertaining to hemostatic changes, blood loss, transfusion management, and postpartum venous thromboembolism prophylaxis in PAS patients. Taken together, the two parts of this review provide a comprehensive survey of challenging aspects in PAS management for anesthesiologists.