Päivi Kannisto

Tertiary lymphoid structures in high-grade serous tubo-ovarian carcinoma: anatomical site matters

Abstract Tertiary lymphoid structures (TLS) in the tumor microenvironment are prognostically beneficial in many solid cancer types. Reports on TLS in high-grade serous tubo-ovarian carcinoma (HGSC) are few, and the prognostic impact is unclear. We investigated mature TLS (mTLS), immature TLS (iTLS) and lymphoid aggregates (LA) in primary adnexal tumors (PTs) and synchronous omental/peritoneal metastases (pMets) of HGSC. Whole H&E slides were scrutinized for mTLS and LA in a population-based cohort of 130 cases with stage III-IV HGSC. The immune cell tumor infiltration was evaluated with single chromogenic immunohistochemistry (IHC) on a tissue microarray (TMA) from the same cases. Selected whole slides (PT n = 11, pMet n = 10) of the cases most abundant in mTLS and LA were further investigated with multiplex IHC and immunofluorescence using digital image analysis (QuPath), to confirm TLS status and map the T and B lymphocyte subtypes. The results showed that mTLS were more common in pMets than in PTs but did not have an independent prognostic impact on overall or progression-free survival. The presence of mTLS correlated with intratumoral infiltration of CD8+ cytotoxic T cells, FOXP3+ regulatory T cells and PD-1+ lymphocytes in pMets only. Although overall mTLS cell composition was similar between PTs and pMets, the outer zones of mTLS in PTs were more immune cell-rich. In conclusion, our results indicate differences in TLS presence and cellular elements between primary adnexal tumors and synchronous peritoneal metastases, which are important to consider when conducting studies of the immune environment in HGSC.

Safe to save blood in ovarian cancer surgery – time to change transfusion habits

Background: Patients with advanced ovarian cancer (AOC) undergoing surgery are often subjected to red blood cell (RBC) transfusions. Both anemia and RBC transfusion are associated with increased morbidity. The aim was to evaluate patient recovery after the implementation of patient blood management (PBM) strategies. Methods: This retrospective cohort study included 354 patients with AOC undergoing surgery at Skane University Hospital Lund, Sweden, between January 2016 and December 2021. The gradual implementation of PBM strategies included restrictive RBC transfusion, tranexamic acid as standard medication before laparotomies and intravenous iron administered to patients with iron deficiency. Severe complications were defined as Clavien-Dindo (CD) grade ≥ 3a. Logistic and linear regression analyses were used to evaluate the differences between three consecutive periods. Results: After the implementation of new strategies, 52% of the patients had at least one transfusion compared to 83% at baseline (p < 0.001). There was no difference in the rate of severe complications (CD ≥ 3a) between the groups, adjusted odds ratio 0.55 (95% CI 0.26–1.17). The mean difference in hemoglobin before chemotherapy was -1.32 g/L (95% CI -3.04 to -0.22) when adjusted for blood loss and days from surgery to chemotherapy. The length of stay (LOS) decreased from 8.5 days to 7.5 days (p 0.002). Interpretation: The number of patients transfused were reduced by 31%. Despite a slight increase in anemia rate, severe complications (CD ≥ 3a) remained stable. The LOS was reduced, and chemotherapy was given without delay, indicating that PBM is feasible and without causing major severe effects on short-term recovery.

Ovarian tumor frozen section, a multidisciplinary affair

Ovarian Cancer (OC) constitute the eighth most common cancers among women worldwide. Surgery remains the cornerstone in the management of OC. Intraoperative frozen section (FS) diagnosis is widely used to decide the surgery course. We aimed to assess the reliability of intraoperative FS diagnosis for treatment planning of patients with suspected OC from a multidisciplinary perspective. The clinical consequences of reclassification and the multidisciplinary management of the therapy plan, is the secondary aim of this study. To our knowledge, this information is sparely investigated. A single-center, retrospective population-based study of patients who underwent surgery for suspected OC between 2018 and 2020. Histopathological outcomes were classified as benign, borderline, or malignant. The FS diagnosis was the diagnostic test, and the final histopathology report was the gold standard. Diagnostic capability for treatment planning was assessed, and modifications made possible by overall clinical knowledge were discussed. A total of 358 patients were identified, of whom 187 were included in the FS group. Overall accuracy was 89.8%, and 19 patients were reclassified; the malignancy grade of 15 tumors was underestimated. Prevalence, sensitivity, specificity, positive predictive value, and negative predictive value for invasive malignancies on FS were 54.0% (CI 46.6-61.3%), 88.1% (CI 80.2-93.7%), 98.8% (CI 93.7-99.9%), 98.9% (CI 92.7-99.8%), and 87.6% (CI 80.6-92.4%), respectively. Tumors incorrectly graded by FS tended to be of borderline-related. The reliability of the FS methodology was an accurate test to help perform appropriate surgery and plan swift oncological treatment. FS is a reliable method to diagnose invasive malignancies and benign pathology. The communication between the pathologist, surgeon, and medical oncologist is highly important for both intraoperative decision-making and postoperative patient care.

Perioperative trajectories of acute-phase proteins and their association with major postoperative complications in advanced ovarian cancer

Acute-phase proteins (APPs) reflect systemic inflammation and nutritional status, yet their perioperative trajectories and clinical utility as biomarkers of outcome in advanced ovarian cancer (aEOC) remain unclear. We aimed to characterise perioperative APP fluctuations and assess their associations with postoperative complications. This observational study included patients undergoing cytoreductive surgery for aEOC across two prospective studies (n = 274). Serial serum albumin, transthyretin, C-reactive protein (CRP), fibrinogen, and procalcitonin were measured preoperatively and on postoperative days (PoD) 1, 3, and 5. Associations between APP levels and major postoperative complications, classified by Clavien-Dindo (CD ≥ III), were examined using multivariable logistic regression. Length of stay (LOS) was evaluated for biomarkers showing significant associations. Predictive thresholds were derived by ROC analysis. Positive APPs peaked postoperatively (CRP and fibrinogen on PoD 3; procalcitonin on PoD 1), while negative APPs reached nadirs on PoD 3. Neither preoperative albumin (>35 g/L) nor transthyretin (>0.2 g/L) predicted major postoperative complications. In contrast, elevated CRP measured on PoD 3 was associated with both major postoperative complications, OR 2.78 (95% CI 1.45-5.48) and prolonged LOS (>7 days) OR 3.0 (95% CI 1.67-5.47), with optimal cut-offs of ≥287 mg/L and ≥322 mg/L respectively (AUC 0.80). Preoperative APPs were not associated with postoperative outcomes in this cohort. CRP measured on postoperative day 3 was the most informative biomarker associated with major postoperative complications and prolonged hospital stay after cytoreductive surgery for advanced ovarian cancer and may support postoperative surveillance and recovery assessment when interpreted alongside clinical findings.