Mihaela Asp

Iron deficiency restrains short-term recovery in patients undergoing surgery for advanced ovarian cancer

Patients with advanced ovarian cancer (AOC) who undergo primary and interval debulking surgery are often anemic at diagnosis, with iron deficiency being the most common cause. The aim was to investigate whether preoperative anemia and iron deficiency impact short-term recovery. This retrospective cohort study included 262 patients with AOC who underwent surgery at Skane University Hospital Lund, Sweden, between January 2020 and December 2023. Patients were divided into four groups, according to preoperative anemia and iron deficiency. Iron deficiency was defined as transferrin saturation (TSAT) < 0.20. Severe complications were defined as Clavien-Dindo (CD) grade ≥3. Logistic regression analyses were used to investigate the difference between patients with and without iron deficiency. Among patients with iron deficiency anemia, 24 % of patients had more than 1 cm of residual tumor at the end of surgery, compared to 6-8 % of patients with no anemia and/or no iron deficiency, (p 0.005). The rate of severe complications (CD ≥ 3) was higher for patients with iron deficiency, odds ratio 2.47 (95 % CI 1.11-5.50), than for patients with no iron deficiency, adjusted for the Aletti score, operating time and hemoglobin (Hb) level. There was no difference between groups regarding length of hospital stay. Patients with iron deficiency anemia, were less likely to undergo radical or optimal surgery. Severe postoperative complications were more common in patients with iron deficiency, with or without anemia. These analyses indicate that iron deficiency is associated with more advanced disease and complex surgical procedures.

Prospective Assessment of Clinically Relevant Fluid Balance Thresholds Associated With Postoperative Complications in Advanced Ovarian Cancer

ABSTRACTBackgroundReliable data on optimal fluid management in the perioperative period for patients with advanced ovarian cancer undergoing cytoreductive surgery is limited. These patients often present with malignant ascites and are prone to significant fluid shifts perioperatively. For this reason, our objective was to define clinical targets for optimal fluid balance and determine whether initial ascites should be included in fluid‐loss calculations by examining the association between perioperative fluid balance and major postoperative complications.MethodsThis prospective, observational study conducted in a centralized and public healthcare system setting in Sweden between 2020 and 2023 included patients with advanced ovarian cancer, &gt; 18 years of age, scheduled for upfront cytoreductive surgery, an ASA physical status I–III with no speech/language issues. The primary outcome was major postoperative complication within 30 days of surgery. The measurements of fluid input and output, cut‐offs for fluid balance, perioperative time, and postoperative complications were defined a priori. The association between fluid balance and major postoperative complications was assessed by multivariable regression, adjusted for predefined covariates, yielding odds ratios (OR) with 95% confidence intervals (CI).ResultsOf 175 enrolled patients, 162 were included in the final analysis. In the adjusted analysis, there was a significant association between fluid balance of 1750–2700 mL, OR 3.40 (95% CI 1.06–10.9; p = 0.04) and &gt; 2700 mL, OR 3.91 (95% CI 1.33–11.5; p = 0.01) and major postoperative complications. When including initial ascites as fluid loss, a balance of &gt; 2700 mL was associated with major postoperative complications, OR 2.59 (95% CI 1.01–6.66, p = 0.047).ConclusionAn optimal target for perioperative fluid balance to decrease the odds of major postoperative complications is suggested to be &lt; 1750 mL. If initial ascites is included as loss in the calculation of balance, the optimal target of fluid balance is suggested to be &lt; 2700 mL. These results provide practical clinical reference values that may assist anesthesiologists and surgical teams in optimizing perioperative fluid management in advanced ovarian cancer.Editorial CommentThis secondary analysis of a trial ovarian cancer operative cohort assessed the relation of the estimated fluid balance over the operative day 24 h to major postoperative complications. The findings showed that the groups where the fluid balance was in the categories higher and also most positive had higher odds for having a major complication compared to the group with lowest fluid balance. Ascities fluid was an issue in this cohort, which was managed in the analysis.Trial Registration: ClinicalTrials.gov: NCT04065009

Effect of intraperitoneal ropivacaine during and after cytoreductive surgery on time-interval to adjuvant chemotherapy in advanced ovarian cancer: a randomised, double-blind phase III trial

In a previous phase II trial, intraperitoneal local anaesthetics shortened the time interval between surgery and adjuvant chemotherapy, an endpoint associated with improved survival in advanced ovarian cancer. Our objective was to test this in a phase III trial. A double-blind, phase III parallel superiority trial was conducted at two university hospitals in Sweden, within a public and centralised healthcare system. Women >18 yr with advanced ovarian cancer scheduled for cytoreductive surgery, an ASA physical status of 1-3 with no speech/language issues, were eligible. Participants were randomly assigned using a central computerised system to receive either ropivacaine 0.2% or saline 0.9% (placebo) intraperitoneally during and after surgery. The primary endpoint was time to return to intended oncologic therapy (RIOT), analysed using t-test and linear regression adjusted for centre. Of the 225 women randomised between August 2020 and December 2023 (ropivacaine n=113; placebo n=112), 175 were included in the modified intention-to-treat analysis (ropivacaine n=86; placebo n=89). Median age: ropivacaine group 64 yr (56-73 yr), placebo group: 66 yr (57-74 yr). The mean RIOT in the ropivacaine group was 26.5 days vs 25.8 days in the placebo group, with a mean difference of 0.7 days (-2.2 to 3.4 days; P=0.65). Per-protocol analysis of 166 women yielded similar results, mean difference of 0.5 days (-2.4 to 3.4 days; P=0.74) days. There were no differences in short-term recovery or postoperative morbidity. Intraperitoneal local anaesthetic did not shorten the time to RIOT among women undergoing surgery for advanced ovarian cancer in this trial. ClinicalTrials.gov (NCT04065009), European Union Clinical Trials Register (2019-003299-38/SE).

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 &lt; 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.

Radiologically enlarged cardiophrenic lymph nodes and CA-125 in relation to diaphragmatic carcinomatosis, surgical outcome, and overall survival in advanced ovarian cancer

We primarily aimed to determine whether the presence of enlarged cardiophrenic lymph nodes (CPLNs), visualized by computed tomography (CT), and CA-125 can be used to assess diaphragmatic carcinomatosis and residual disease (RD) in advanced ovarian cancer (AOC) patients treated with upfront surgery. The secondary aim was to determine the prognostic role of CT-CPLNs in overall survival (OS). A single-center, retrospective, population-based study was conducted of patients who underwent surgery for AOC from January 1, 2014-December 31, 2018. Suspicious CT-CPLNs were defined as having a short axis ≥5 mm. The median survival and rate of survival were calculated with the Kaplan-Meier method using multivariate Cox regression analyses, including comparisons of complete cytoreductive surgery (CCS; defined as the complete removal of all intra-abdominal tumor) versus noncomplete cytoreductive surgery (non-CCS) and analyses related to CT-CPLN status and preoperative CA-125 values. We included 208 patients. CT-CPLNs correlated with both diaphragmatic carcinomatosis (OR 3.59, 95% CI 1.81-7.16, Enlarged CPLNs on CT scans and CA-125 levels correlate with diaphragmatic carcinomatosis and RD at the end of the surgery. The strongest prognostic factor for OS remains CCS, regardless of the CT-CPLN status.

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.

The role of computed tomography in the assessment of tumour extent and the risk of residual disease after upfront surgery in advanced ovarian cancer (AOC)

Abstract Purpose Epithelial ovarian cancer is usually diagnosed in the advanced stages. To choose the best therapeutic approach, an accurate preoperative assessment of the tumour extent is crucial. This study aimed to determine whether the peritoneal cancer index (PCI), the amount of ascites, and the presence of cardiophrenic nodes (CPLNs) visualized by computed tomography (CT) can assess the tumour extent (S-PCI) and residual disease (RD) for advanced ovarian cancer (AOC) patients treated with upfront surgery. Methods In total, 118 AOC cases were included between January 2016 and December 2018 at Skåne University Hospital, Lund, Sweden. Linear regression and interclass correlation (ICC) analyses were used to determine the relationship between CT-PCI and S-PCI. The patients were stratified in complete cytoreductive surgery (CCS) with no RD or to non-CCS with RD of any size. The amount of ascites on CT (CT-ascites), CA-125 and the presence of radiological enlarged CPLNs (CT-CPLN) were analysed to evaluate their impact on estimating RD. Results CT-PCI correlated well with S-PCI (0.397; 95% CI 0.252–0.541; p &lt; 0.001). The risk of RD was also related to CT-PCI (OR 1.069 (1.009–1.131), p &lt; 0.023) with a cut-off of 21 for CT-PCI (0.715, p = 0.000). The sensitivity, specificity, positive predictive value and negative predictive value were 58.5, 70.3, 52.2 and 75.4%, respectively. CT-ascites above 1000 ml predicted RD (OR 3.510 (1.298–9.491) p &lt; 0.013). Conclusion CT is a reliable tool to assess the extent of the disease in advanced ovarian cancer. Higher CT-PCI scores and large volumes of ascites estimated on CT predicted RD of any size.

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.

The IPLA-OVCA Trial, Intra-Peritoneal Local Anaesthetics in Ovarian Cancer

Surgery and chemotherapy combined constitute first line treatment in women with advanced ovarian cancer. The aim of surgery apart from staging is cytoreduction, i.e. surgical resection of tumour. Radical resection of all tumour visible by the naked eye followed by adjuvant chemotherapy is associated with best chance of prolonged survival. However, because of tumour dissemination in the peritoneal cavity, radical surgery is often very extensive with surgery in all quadrants of the abdomen and multi-organ resection with substantial risk of postoperative severe complications and subsequent delay in administration of adjuvant chemotherapy. Longer time-interval between surgery to start of adjuvant chemotherapy has been associated with decrease in survival. Surgery presents opportunities not only for eradicating tumours but, paradoxically, also for proliferation and invasion of residual cancer cells. It increases the shedding of malignant cells into the blood and lymphatic circulations, inhibits their apoptosis and potentiates their invasion capacity. Additionally, the immune system, the inflammatory system and the neuroendocrine system react to surgery with important changes, which have been proven to promote progression of cancer. Several anaesthesia-related factors play an important role in perioperative tumorigenesis such as inhalational anaesthetics, opiate analgesics, local anaesthetics and regional anaesthesia, all of which may impact short-term morbidity and long-term mortality. A previous randomized placebo-controlled pilot study suggests that women who receive local anesthetics intraperitoneally preoperatively have a significantly decreased time-interval to initiation of adjuvant chemotherapy. In a prospective, randomised, multi-centre study, we plan to further assess if intraperitoneal local anaesthetics administered perioperatively during 72 h leads to early start of chemotherapy compared to placebo in patients undergoing cytoreductive surgery for FIGO stage III-IV ovarian cancer.