Andreas Kleppe

Prospective evaluation of an enhanced recovery after surgery (ERAS) pathway in a Norwegian cohort of patients with suspected or advanced ovarian cancer

This prospective cohort study evaluated the introduction of an enhanced recovery after surgery (ERAS) pathway in a tertiary gynecologic oncology referral center. Compliance and clinical outcomes were studied in two separate surgical cohorts. Patients undergoing laparotomy for suspected or verified advanced ovarian cancer at Oslo University Hospital were prospectively included in a pre- and post-implementation cohort. A priori, patients were stratified into: cohort 1, patients planned for surgery of advanced disease; and cohort 2, patients undergoing surgery for suspicious pelvic tumor. Baseline characteristics, adherence to the pathway, and clinical outcomes were assessed. Of the 439 included patients, 235 (54%) underwent surgery for advanced ovarian cancer in cohort 1 and 204 (46%) in cohort 2. In cohort 1, 53% of the patients underwent surgery with an intermediate/high Aletti complexity score. Post-ERAS, median fasting times for solids (13.1 hours post-ERAS vs 16.0 hours pre-ERAS, p<0.001) and fluids (3.7 hours post-ERAS vs 11.0 hours pre-ERAS, p<0.001) were significantly reduced. Peri-operative fluid management varied less and was reduced from median 15.8 mL/kg/hour (IQR 10.8-22.5) to 11.5 mL/kg/hour (IQR 9.0-15.4) (p<0.001). In cohort 2 only there was a statistically significant reduction in length of stay (mean (SD) 4.3±1.5 post-ERAS vs 4.6±1.2 pre-ERAS, p=0.026). Despite stable readmission rates, there were significantly more serious complications reported in cohort 1 post-ERAS. ERAS increased adherence to current standards in peri-operative management with significant reduction in fasting times for both solids and fluids, and peri-operative fluid administration. Length of stay was reduced in patients with suspicious pelvic tumor. Despite serious complications being common in patients with advanced disease undergoing debulking surgery, a causal relationship with the ERAS protocol could not be established. Implementing ERAS and continuous performance auditing are crucial to advancing peri-operative care of patients with ovarian cancer.

Prognostic value of tertiary lymphoid structures in molecular subgroups of endometrial carcinoma

Tertiary lymphoid structures, lymphoid cell clusters formed in response to cancer or chronic disease, serve as a prognostic marker in multiple cancer types, including endometrial carcinoma. We assessed the prognostic significance of tertiary lymphoid structures, using the surrogate marker L1 cell adhesion molecule (L1CAM), in 1208 endometrial carcinoma patients in all stages, histological subtypes, and risk groups. Immunohistochemical evaluation of L1CAM in 1 tissue section from each patient revealed tertiary lymphoid structure-positivity in 287 of 1208 (23.8%) cases. In univariable analyses, patients with tertiary lymphoid structure-positive tumors had significantly longer time to recurrence (HR 0.61, p < .001) and cancer-specific survival (HR 0.53, p < .001) compared to patients with tumors without tertiary lymphoid structures. In multivariable analyses with standard clinical and pathological markers as well as modern molecular classification, the presence of tertiary lymphoid structures was an independent prognostic marker for time to recurrence (HR 0.63, p < .001) and cancer-specific survival (HR 0.54, p < .001). The presence of tertiary lymphoid structures was more frequent in POLE-mutated (59.4%) and mismatch repair deficient (32.3%) compared to p53-abnormal (15.8%) and no specific molecular profile (14.7%) tumors. In patients with p53-abnormal tumors, the presence of tertiary lymphoid structures was significantly associated with better outcomes for both time to recurrence (HR 0.51, p = .014) and cancer-specific survival (HR 0.52, p = .021) in multivariable analyses. These findings suggest that the evaluation of tertiary lymphoid structures by L1CAM may enhance prognostic precision in endometrial carcinoma.