Emergency delivery in case of suspected placenta accreta spectrum: Can it be predicted?

INTRODUCTION: The main goal of placenta accreta spectrum (PAS) screening is to enable delivery in an expert center in the presence of an experienced team at an appropriate time. Our study aimed to identify independent risk factors for emergency deliveries within the IS-PAS 2.0 database cohort and establish a multivariate predictive model. MATERIAL AND METHODS: A retrospective analysis of prospectively collected PAS cases from the IS-PAS database between January 2020 and June 2022 by 23 international expert centers was performed. All PAS cases (singleton and multiple pregnancies) managed according to local protocols were included. Individuals with emergent delivery were identified and compared to those with scheduled delivery. A multivariate analysis was conducted to identify the possible risk factors for emergency delivery and was used to establish a predictive model. Maternal outcomes were compared. RESULTS: Overall, 315 women were included in the study. Of these, 182 participants (89 with emergent and 93 with scheduled delivery) were included in the final analysis after exclusion of those with unsuspected PAS antenatally or who lacked information about the urgency of delivery. Gestational age at delivery was higher in the scheduled group (34.7 vs. 32.9, p < 0.001). Antenatal bleeding (OR 2.9, p = 0.02) and a placenta located over a uterine scar (OR 0.38, p = 0.001) were the independent predictive factors for emergent delivery (AUC 0.68). Ultrasound (US) markers: loss of clear zone (p = 0.001), placental lacunae (p = 0.01), placental bulge (p = 0.02), and presence of bridging vessels (p = 0.02) were more frequently documented in the scheduled group. None of these markers improved the predictive values of the model. Higher PAS grades were identified in the scheduled group (p = 0.01). There were no significant differences in maternal outcomes. CONCLUSIONS: Antenatal bleeding and the placental location away from the uterine scar remained the most significant predictors for emergent delivery among patients with PAS, even when combining more predictive risk factors, including US markers. Based on these results, patients who bleed antenatally may benefit from transfer to an expert center, as we found no differences in maternal outcomes between groups delivered in expert centers. Earlier-scheduled delivery is not supported due to the low predictive value of our model.

Efficacy of locoregional analgesic techniques after laparotomy for gynecologic cancer: a systematic review.

OBJECTIVE: To determine which locoregional techniques are effective in managing post-operative pain in major open oncologic gynecologic surgery in terms of pain scores and opioid consumption when epidural analgesia is not a feasible option. METHODS: A systematic review of the literature, based on the Preferred Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines, was conducted. The ROB-2 assessment was used to assess bias. The primary outcomes were opioid consumption and post-operative pain scores. Secondary outcomes included post-operative markers such as time to mobilization and bowel movement. RESULTS: A total of nine studies (n=714) were included in the analysis. Eight studies had a low risk of bias. Five different forms of locoregional analgesia were described. Eight studies compared with placebo and one study compared rectus sheath block with epidural analgesia. Three of the five studies investigating transversus abdominis plane (TAP) blocks showed an improvement in pain scores and opioid consumption when compared with the placebo group. One study investigating rectus sheath blocks and another investigating paravertebral blocks demonstrated significantly less opioid consumption and improved pain scores at certain time points. The studies investigating continuous wound infiltration and superior hypogastric plexus block found no significant effect. No adverse effects of locoregional anesthesia were found. CONCLUSION: Our study showed that TAP blocks, rectus sheath blocks, and paravertebral blocks may decrease opioid consumption and improve pain scores in patients undergoing open abdominal surgery for gynecologic cancer. Additionally, these techniques might serve as a viable alternative for patients with contraindications to epidural analgesia.

Prevalence of fetal anomalies, stillbirth, neonatal morbidity, or mortality in pregnancies complicated by placenta accreta spectrum disorders.

INTRODUCTION: Placenta accreta spectrum disorders (PAS) lead to major complications in pregnancy. While the maternal morbidity associated with PAS is well known, there is less information regarding neonatal morbidity in this setting. The aim of this study is to describe the neonatal outcomes (fetal malformations, neonatal morbidity, twin births, stillbirth, and neonatal death), using an international multicenter database of PAS cases. MATERIAL AND METHODS: This was a prospective, multicenter cohort study based on prospectively collected cases, using the international multicenter database of the International Society for PAS, carried out between January 2020 and June 2022 by 23 centers with experience in PAS care. All PAS cases were included, regardless of whether singleton or multiple pregnancies and were managed in each center according to their own protocols. Data were collected via chart review. Local Ethical Committee approval and Data Use Agreements were obtained according to local policies. RESULTS: There were 315 pregnancies eligible for inclusion, with 12 twin pregnancies, comprising 329 fetuses/newborns; 2 cases were excluded due to inconsistency of data regarding fetal abnormalities. For the calculation of neonatal morbidity and mortality, all elective pregnancy terminations were excluded, hence 311 pregnancies with 323 newborns were analyzed. In our cohort, 3 neonates (0.93%) were stillborn; of the 320 newborns delivered, there were 10 cases (3.13%) of neonatal death. The prevalence of major congenital malformations was 4.64% (15/323 newborns), most commonly, cardiovascular, central nervous system, and gastrointestinal tract malformations. The overall prevalence of major neonatal morbidity in pregnancies complicated by PAS was 47/311 (15.1%). There were no stillbirths, neonatal deaths, or fetal malformations in reported twin gestations. CONCLUSIONS: Although some outcomes may be too rare to detect within our cohort and data should be interpreted with caution, our observational data supports reassuring neonatal outcomes for women with PAS.

Unraveling Differences in Molecular Mechanisms and Immunological Contrasts between Squamous Cell Carcinoma and Adenocarcinoma of the Cervix.

This study aims to refine our understanding of the inherent heterogeneity in cervical cancer by exploring differential gene expression profiles, immune cell infiltration dynamics, and implicated signaling pathways in the two predominant histological types of cervix carcinoma, Squamous Cell Carcinoma (SCC) and Adenocarcinoma (ADC). Targeted gene expression data that were previously generated from samples of primary cervical cancer were re-analyzed. The samples were grouped based on their histopathology, comparing SCC to ADC. Each tumor in the study was confirmed to be high risk human papilloma virus (hrHPV) positive. A total of 21 cervical cancer samples were included, with 11 cases of SCC and 10 of ADC. Data analysis revealed a total of 26 differentially expressed genes, with 19 genes being overexpressed in SCC compared to ADC (Benjamini-Hochberg (BH)-adjusted p-value < 0.05). Importantly, the immune checkpoint markers CD274 and CTLA4 demonstrated significantly higher expression in SCC compared to ADC. In addition, SCC showed a higher infiltration of immune cells, including B and T cells, and cytotoxic cells. Higher activation of a variety of pathways was found in SCC samples including cytotoxicity, interferon signaling, metabolic stress, lymphoid compartment, hypoxia, PI3k-AKT, hedgehog signaling and Notch signaling pathways. Our findings show distinctive gene expression patterns, signaling pathway activations, and trends in immune cell infiltration between SCC and ADC in cervical cancer. This study underscores the heterogeneity within primary cervical cancer, emphasizing the potential benefits of subdividing these tumours based on histological and molecular differences.

Hormone Receptor Expression and Activity for Different Tumour Locations in Patients with Advanced and Recurrent Endometrial Carcinoma.

BACKGROUND: Response to hormonal therapy in advanced and recurrent endometrial cancer (EC) can be predicted by oestrogen and progesterone receptor immunohistochemical (ER/PR-IHC) expression, with response rates of 60% in PR-IHC > 50% cases. ER/PR-IHC can vary by tumour location and is frequently lost with tumour progression. Therefore, we explored the relationship between ER/PR-IHC expression and tumour location in EC. METHODS: Pre-treatment tumour biopsies from 6 different sites of 80 cases treated with hormonal therapy were analysed for ER/PR-IHC expression and classified into categories 0-10%, 10-50%, and >50%. The ER pathway activity score (ERPAS) was determined based on mRNA levels of ER-related target genes, reflecting the actual activity of the ER receptor. RESULTS: There was a trend towards lower PR-IHC (33% had PR > 50%) and ERPAS (27% had ERPAS > 15) in lymphogenic metastases compared to other locations (p = 0.074). Hematogenous and intra-abdominal metastases appeared to have high ER/PR-IHC and ERPAS (85% and 89% ER-IHC > 50%; 64% and 78% PR-IHC > 50%; 60% and 71% ERPAS > 15, not significant). Tumour grade and previous radiotherapy did not affect ER/PR-IHC or ERPAS. CONCLUSIONS: A trend towards lower PR-IHC and ERPAS was observed in lymphogenic sites. Verification in larger cohorts is needed to confirm these findings, which may have implications for the use of hormonal therapy in the future.

Opportunities for, and barriers to, uterus-preserving surgical techniques for placenta accreta spectrum.

INTRODUCTION: Placenta accreta spectrum (PAS) can lead to major peripartum morbidity. Appropriate management approaches depend on the clinical severity, each individual's preference, and the treating team's expertise. Peripartum hysterectomy is the most frequently used treatment option. However, it can impact psychological well-being and fertility. We investigated whether conservative treatment with focal resection or leaving the placenta in situ is associated with comparable or lower maternal morbidity than hysterectomy in centers of excellence within the International Society for placenta accreta spectrum (IS-PAS). Furthermore, a survey was conducted to explore potential barriers to conservative management in antenatal counseling and intraoperative decision-making. MATERIAL AND METHODS: Confirmed PAS cases in the prospective IS-PAS database from 22 registered centers between January 2020 and June 2022 were included in the analysis. A separate online survey with 21 questions was answered by the IS-PAS center experts about indications, diagnostic criteria, patient counseling, surgical practice, changes from the preoperative treatment plan, and why conservative management may not be offered. RESULTS: A total of 234 cases were included in the analysis: 186 women received hysterectomy and 38 women were treated by focal resection, and 10 by leaving the placenta in situ. Blood loss was lower in the focal resection group and in the placenta in situ group compared to the hysterectomy group (p = 0.04). 46.4% of the women initially planned for focal resection, and 35.7% of those initially planned for leaving the placenta in situ were ultimately treated by hysterectomy. Our survey showed that the IS-PAS centers preferred hysterectomy according to a woman's wishes (64%) and when they expected less blood loss and morbidity (41%). Eighteen percent of centers did not offer focal resection at all due to a lack of experience with this technique. Reasons for not offering to leave the placenta in situ were avoidance of unexpected reoperation (36%), puerperal infection (32%), or skepticism about the method (23%). CONCLUSIONS: Uterus-preserving treatment strategies such as focal resection appear to be safe alternatives to peripartum hysterectomy. However, less than half of the IS-PAS centers perform them. Acceptance of conservative treatments could be increased by standardized criteria for their implementation and by systematic training for PAS experts.

Survival of Women with Advanced Stage Cervical Cancer: Neo-Adjuvant Chemotherapy Followed by Radiotherapy and Hyperthermia versus Chemoradiotherapy.

AIM: To investigate and compare overall survival (OS), disease-free survival (DFS) and toxicity of women who underwent either chemoradiotherapy with or without prior lymph node debulking or upfront chemotherapy followed by radiotherapy and hyperthermia (triple therapy) for locally advanced cervical cancer (LACC) to identify a potential role for triple therapy. METHODS: Women with histologically proven LACC and with International Federation of Gynecology and Obstetrics (FIGO) 2009 stage IB2 and IIA2 to IVA were included. Cox regression analyses were used for calculating hazard ratios and to adjust for confounding variables. A multivariable logistic regression analysis was used to examine the influence of covariates on toxicity. RESULTS: A total of 370 patients were included of whom 58% (n = 213) received chemoradiotherapy (CRT), 18% (n = 66) received node-debulking followed by chemoradiotherapy (LND-CRT) and 25% (n = 91) received triple therapy (TT). Five-year OS was comparable between the three treatment groups, with 53% (95% confidence interval 46-59%) in the CRT group, 45% (33-56%) in the LND-CRT group and 53% (40-64%) in the TT group (p = 0.472). In the adjusted analysis, 5-year OS and DFS were comparable between the three treatment groups. No chemotherapy-related differences in toxicity were observed. CONCLUSION: This study suggests that the toxicity and survival of TT is similar to CRT or LND-CRT.

Transabdominal and transvaginal ultrasound findings help to guide the clinical management of placenta accreta spectrum cases.

INTRODUCTION: The clinical management of placenta accreta spectrum (PAS) depends on placental topography and vascular involvement. Our aim was to determine whether transabdominal and transvaginal ultrasound signs can predict PAS management. MATERIAL AND METHODS: We conducted a retrospective cohort study of consecutive prenatally suspected PAS cases in a single tertiary-care PAS center between January 2021 and July 2022. When PAS was confirmed during surgery, abdominal and transvaginal ultrasound scans were analyzed in relation to PAS management. The preferred surgical approach of PAS was one-step conservative surgery (OSCS). Massive blood loss and PAS topography in the lower bladder trigone necessitated cesarean hysterectomy. Transvaginal ultrasound-diagnosed intracervical hypervascularity was split into three categories based on their quantity. Anatomically, the internal cervical os is located at the level of the bladder trigone and was used as landmark for upper and lower bladder trigone PAS. RESULTS: Ninety-one women underwent OSCS and 35 women underwent cesarean hysterectomy (total 126 women with PAS). Abdominal and transvaginal ultrasound features differed significantly between women that underwent OSCS and cesarean hysterectomy: decreased myometrial thickness (<1 mm), 82.4% vs. 100%, p = 0.006; placental bulge, 51.6% vs. 94.3%, p < 0.001; bladder wall interruption, 62.6% vs. 97.1%, p < 0.001; abnormal placental lacunae, 75.8% vs. 100%, p < 0.001; hypervascularity (large lacunae feeding vessels, 57.8% vs. 94.6%, p < 0.001; parametrial hypervascularity, 15.4% vs. 60%, p < 0.001; the rail sign, 6.6% vs. 28.6%, p = 0.003; three-dimensional Doppler intra-placental hypervascularity, 81.3% vs. 100%, p < 0.001; intracervical hypervascularity 60.4% vs. 94.3%, p < 0.001); and cervical length 2.5 ± 0.94 vs. 2.2 ± 0.73, p = 0.038. Other ultrasound signs were not significantly different. The results of multivariable logistic regression showed placental bulge (odds ratio [OR] 9.3; 95% CI 1.9-44.3; p = 0.005), parametrial hypervascularity (OR 4.1; 95% CI 1.541-11.085; p = 0.005), and intracervical hypervascularity (OR 9.2; 95% CI 1.905-44.056; p = 0.006) were weak predictors of OSCS. Intracervical hypervascularity Grade 1 (vascularity <50% of cervical tissue) was more present in OSCS than higher gradings two and three (91% vs. 27.6% vs. 14.3%; p < 0.001). CONCLUSIONS: Cesarean hysterectomy is associated with the PAS signs of placental bulge and Grade 2 and 3 intracervical hypervascularity. OSCS is associated with intracervical hypervascularity Grade 1 on transvaginal ultrasound. Prospective validation is required to formulate predictors for PAS management.

Cytoreductive Surgery with the PlasmaJet Improved Quality-of-Life for Advanced Stage Ovarian Cancer Patients.

BACKGROUND: Knowledge of quality-of-life after cytoreductive surgery is important to counsel patients with advanced-stage epithelial ovarian cancer prior to surgery. The aim of this study was to determine whether the use of the PlasmaJet Surgical device during cytoreductive surgery has an effect on the quality-of-life of patients with advanced epithelial ovarian cancer. METHODS: Data included in this prospective observational study were derived from the PlaComOv study, in which patients with advanced epithelial ovarian cancer were randomly assigned to have cytoreductive surgery with or without adjuvant use of the PlasmaJet. Quality-of-life was measured before surgery and one, six, 12, and 24 months after surgery with three questionnaires: the EORTC QLQ-C30, QLQ-OV28, and EQ-5D-5L. RESULTS: Between 2018 and 2020, 326 patients were enrolled in the trial. The overall response rate was high, with the lowest response rate at 24 months of 77%. At 6 months, quality-of-life was higher in the intervention group (95%CI 0.009; 0.081, p = 0.045). At 12 months, quality-of-life was higher in the intervention group with fewer symptoms of fatigue, appetite loss, and diarrhea (95%CI 0.6; 10,0, p = 0.027); similarly, patients in the intervention group reported a better body image (95%CI -14.2; -3.0, p = 0.003) and a higher score on the visual analog scale (95%CI 1.99; 11.15, p = 0.005). At 24 months postoperatively, no further difference was found between the two groups except for pain (95%CI -12.9; -0.8, p = 0.027) and body image (95%CI -13.808; -0.733, p = 0.029). A higher quality-of-life in the intervention group was partially explained by the mediator 'surgery outcome'. CONCLUSIONS: This study demonstrated knowledge of patients' quality-of-life until two years after cytoreductive surgery. The use of the PlasmaJet Surgical device during cytoreductive surgery leads to a higher quality-of-life than conventional surgery with electrocoagulation alone. Even after adjustment for the mediator of surgical outcome, a higher quality-of-life was seen in patients who had surgery with the use of the PlasmaJet device.

Serous endometrial intra-epithelial carcinoma: an observational study.

BACKGROUND: Serous endometrial intra-epithelial carcinoma is described as a malignant, superficial spreading lesion with risk of extra-uterine spread at time of diagnosis, and poor outcome. OBJECTIVE: To evaluate the surgical management of patients with serous endometrial intra-epithelial carcinoma and its impact on oncologic outcomes and complications. METHODS: This Dutch observational retrospective cohort study evaluated all patients diagnosed with pure serous endometrial intra-epithelial carcinoma in the Netherlands, between January 2012 and July 2020. The pathological examination was reviewed by two pathologists with expertise in gynecological oncology. Clinical data were obtained when the diagnosis was confirmed. Primary outcome is progression-free survival, secondary outcomes are duration of follow-up, adverse events related to surgery, and overall survival. RESULTS: A total of 23 patients from 13 medical centers were included, of whom 15 (65.2%) presented with post-menopausal blood loss. In 17 patients (73.9%) the intra-epithelial lesion was present in an endometrial polyp. All patients underwent hysterectomy, of whom 12 patients (52.2%) were surgically staged. None of the staged patients showed extra-uterine disease. Two patients received adjuvant brachytherapy. There were no recurrences of disease (median follow-up duration of 35.6 months (range 1.0-108.6) and no disease-related deaths in this cohort. CONCLUSION: In patients with serous endometrial intra-epithelial carcinoma, median progression-free survival reached nearly 3 years and no recurrences have been reported. Our results do not endorse World Health Organization 2014 advice to treat serous endometrial intra-epithelial carcinoma as high-grade, high-risk endometrial carcinoma. Full surgical staging might possibly lead to overtreatment.

Pelvic lymph node dissection for cervical or bladder cancer: embedding residual fat tissue offers no added value.

Diagnosis of lymph node metastases in pelvic lymph node dissection (PLND) is important for staging and treatment. Standard practice is to submit visible or palpable lymph nodes for histology. We assessed the added value of embedding all residual fatty tissue.Patients (n = 85) who underwent PLND for cervical (n = 50) or bladder cancer (n = 35) between 2017 and 2019 were included. Study approval was obtained (MEC-2022-0156, 18.03.2022, retrospectively registered).The median lymph node yield with conventional pathological dissection was 21 nodes (Interquartile range (IQR) 18-28). This led to discovery of positive lymph nodes in 17 (20%) patients. Extended pathological assessment found 7 (IQR 3-12) additional nodes, but did not result in identification of more node metastases.Histopathological analysis of residual fatty tissue harvested at PLND resulted in an increased lymph node yield, but not in the detection of additional lymph node metastases.

Patient-Reported Mobility, Physical Activity, and Bicycle Use after Vulvar Carcinoma Surgery.

Patients treated for vulvar carcinoma may experience losses in mobility and physical activity. In this study, we assess the prevalence and severity of mobility problems using patient-reported outcomes of three questionnaires: EQ-5D-5L to estimate QoL and perceived health; SQUASH to estimate habitual physical activity; and a problem-specific questionnaire on bicycling. Patients treated for vulvar carcinoma between 2018 and 2021 were recruited, and 84 (62.7%) responded. The mean age was 68 ± 12 years (mean ± standard deviation). Self-reported QoL and perceived health were 0.832 ± 0.224 and 75.6 ± 20.0, respectively. Dutch physical activity guidelines were met by 34.2% of participants. Compared to baseline values, the times spent walking, bicycling, and participating in sports were all reduced. During bicycling, patients experienced moderate or severe pain in the skin of the vulva (24.5%), pain in the sit bones (23.2%), chafing (25.5%), or itching (8.9%). Overall, 40.3% experienced moderate or severe bicycling problems or could not bicycle, 34.9% felt that their vulva impeded bicycling, and 57.1% wished to make more or longer bicycling journeys. To conclude, vulvar carcinoma and its treatment reduce self-reported health, mobility, and physical activity. This motivates us to investigate ways to reduce discomfort during physical activities, and help women regain their mobility and self-reliance.

Plasma Device Functions and Tissue Effects in the Female Pelvis-A Systematic Review.

Medical use of (non-)thermal plasmas is an emerging field in gynaecology. However, data on plasma energy dispersion remain limited. This systematic review presents an overview of plasma devices, fields of effective application, and impact of use factors and device settings on tissues in the female pelvis, including the uterus, ovaries, cervix, vagina, vulva, colon, omentum, mesenterium, and peritoneum. A search of the literature was performed on 4 January 2023 in the Medline Ovid, Embase, Cochrane, Web of Science, and Google Scholar databases. Devices were classified as plasma-assisted electrosurgery (ES) using electrothermal energy, neutral argon plasma (NAP) using kinetic particle energy, or cold atmospheric plasma (CAP) using non-thermal biochemical reactions. In total, 8958 articles were identified, of which 310 were scanned, and 14 were included due to containing quantitative data on depths or volumes of tissues reached. Plasma-assisted ES devices produce a thermal effects depth of <2.4 mm. In turn, NAP effects remained superficial, <1.0 mm. So far, the depth and uniformity of CAP effects are insufficiently understood. These data are crucial to achieve complete treatment, reduce recurrence, and limit damage to healthy tissues (e.g., prevent perforations or preserve parenchyma). Upcoming and potentially high-gain applications are discussed, and deficits in current evidence are identified.

Clinical validation and comparison of the Comprehensive Complication Index and Clavien-Dindo classification in predicting post-operative outcomes after cytoreductive surgery in advanced ovarian cancer.

OBJECTIVE: The Comprehensive Complication Index (CCI) is an instrument used to measure cumulative post-operative complications. Our study aimed to validate the CCI after cytoreductive surgery for primary advanced-stage epithelial ovarian cancer, and to compare its diagnostic performance with the Clavien-Dindo classification. METHODS: This prospective cohort study classified post-operative complications according to the Clavien-Dindo classification and the CCI. Logistic regression was used to determine the association between both classifications with intensive care unit admission, prolonged length of hospital stay (defined as stays longer than the 75th percentile of all stays in this study), 30-day readmission, and time to initiating chemotherapy after surgery >42 days. Area under the receiver operating characteristic curves (AUC) were used to assess the discriminative performance of each classification. RESULTS: A total of 300 patients were included in the analysis. Most patients (n=255, 85%) underwent interval cytoreductive surgery. Complete cytoreduction was achieved in 235 (78%) patients. Overall, 30-day post-operative complications classified by the Clavien-Dindo classification occurred in 147 (49%) patients. Severe complications (grade ≥3a) occurred in 51 (17%) patients. Approximately 30% (n=82) had multiple complications. The CCI showed an excellent correlation with the Clavien-Dindo classification (r=0.906, p<0.001). In comparison with the Clavien-Dindo classification, the proportion of patients classified with severe complications increased from 17% to 30% when stratified with the CCI, and 20% of patients were diagnosed with a CCI score that correlated with a higher Clavien-Dindo classification grade. On regression analysis, both Clavien-Dindo classification and CCI had associations with intensive care unit admission, prolonged length of hospital stay, 30-day readmission, and time to chemotherapy >42 days (all p<0.05). AUC demonstrated that CCI (0.842, 95% CI 0.792 to 0.893) and Clavien-Dindo classification (0.813, 95% CI 0.762 to 0.864, p<0.001) had a good diagnostic performance for prolonged length of hospital stay. CONCLUSIONS: Both the Clavien-Dindo classification and CCI showed significant associations with all surgical outcomes. However, the cumulative complications score of the CCI demonstrated a more superior discriminative performance than the Clavien-Dindo classification for prolonged length of hospital stay in advanced-stage epithelial ovarian cancer.

The effects of neutral argon plasma versus electrocoagulation on tissue in advanced-stage ovarian cancer: a case series.

BACKGROUND: The aim of surgery for advanced-stage ovarian cancer is a complete cytoreduction, because this is the most important independent prognostic factor for prolonged survival. Yet this can be difficult to achieve when there are micrometastases on the intestinal mesentery or intestines. The PlasmaJet device is an instrument to remove these micrometastases, but little is known about the depth of damage in human tissue compared to electrocoagulation devices. METHODS: A prospective study was performed for the ex-vivo comparison of the histological depth of thermal damage of neutral argon plasma (PlasmaJet®) and electrocoagulation devices, in a series of 106 histological slides of 17 advanced-stage ovarian cancer patients. Depending on the tissue types resected during complete cytoreductive surgery, samples were collected from reproductive organs (uterus, ovaries), intestines (ileum, colon, rectum) and omentum, intestinal mesentery and peritoneum. RESULTS: Average thermal damage depth was 0.15 mm (range 0.03-0.60 mm) after use of neutral argon plasma and 0.33 mm (range 0.08-1.80 mm) after use of electrocoagulation (p < 0.001). Greater disruption of the tissue surface was often observed after electrocoagulation. CONCLUSION: Our case series suggests that the use of neutral argon plasma during cytoreductive surgery produces significantly less thermal damage than electrocoagulation treatment. It is therefore considered a thermally safe alternative, aiding in the achievement of cytoreductive surgery.

Preoperative Cancer Antigen 125 Level as Predictor for Complete Cytoreduction in Ovarian Cancer: A Prospective Cohort Study and Systematic Review.

Background: The tumor marker 'cancer antigen 125' (CA-125) plays a role in the management of women with advanced stage ovarian cancer. This study aims to describe the predictive value of pre-treatment CA-125 level and the reduction after neoadjuvant chemotherapy (NACT) on surgical outcome. Methods: A systematic review and a prospective clinical study were performed. Multiple databases were searched from database inception to April 2022. The clinical study is part of a randomized controlled trial named "PlaComOv-study". A regression analysis was performed to demonstrate correlations between preoperative CA-125 levels, CA-125 reduction after NACT, and surgical outcome. Results: Fourteen relevant articles were analyzed of which eleven reported that lower preoperative CA-125 levels were associated with a higher probability of complete cytoreduction. In the clinical study, 326 patients with FIGO stage IIIB-IV ovarian cancer who underwent CRS were enrolled from 2018 to 2020. Patients who underwent interval CRS with preoperative CA-125 levels ≤35 kU/L had higher odds of achieving complete CRS than patients with CA-125 level >35 kU/L (85% vs. 67%, OR 2.79, 95%CI 1.44−5.41, p = 0.002). In multivariable analysis with presence of ascites and peritoneal carcinomatosis, normalized preoperative CA-125 did not appear as a significant predictor for complete CRS. Conclusions: In literature, preoperative CA-125 levels ≤35 kU/L were associated with a significant higher percentage of complete CRS in univariable analysis. According to our cohort study, preoperative CA-125 level ≤35 kU/L cannot independently predict surgical outcome either for primary or interval CRS.

Cost Study of the PlasmaJet Surgical Device Versus Conventional Cytoreductive Surgery in Patients With Advanced-Stage Ovarian Cancer.

PURPOSE: Adjuvant use of Neutral Argon Plasma (PlasmaJet Surgical Device) during cytoreductive surgery (CRS) for advanced-stage epithelial ovarian cancer improves surgical outcomes. The aim of this study is to examine the costs of adjuvant use of the PlasmaJet during surgery compared with conventional CRS in advanced-stage epithelial ovarian cancer. MATERIALS AND METHODS: The patients were randomly assigned to surgery with or without the PlasmaJet. Analysis of the intra- and extramural health care costs was performed. Costs were divided into three categories: costs of the diagnostic phase (T1), inpatient care up to discharge including costs of surgery (T2), and outpatient care including chemotherapy until 6 weeks after the last cycle of chemotherapy (T3). RESULTS: Overall, 327 patients underwent CRS (surgery with PlasmaJet: n = 157; conventional surgery: n = 170). The mean total health costs were significantly higher for CRS with adjuvant use of PlasmaJet compared with conventional CRS (€19,414 v €18,165, P = .017). Costs are divided into costs of the diagnostic phase (€2,034 v €1,974, P = .890), costs of inpatient care (€10,956 v €9,556, P = .003), and costs of outpatient care (€6,417 v €6,628, P = .147). CONCLUSION: Mean total health care costs of the use of PlasmaJet in CRS were significantly higher than those for conventional CRS. This difference is fully explained by the additional surgery costs of the use of PlasmaJet. However, surgery with the use of the PlasmaJet leads to a significantly higher percentage of complete CRS and a halving of stomas. A cost-effectiveness analysis will be performed once survival data are available (funded by ZonMw, Trial Register NL62035.078.17).

Factors Predicting 30-Day Grade IIIa-V Clavien-Dindo Classification Complications and Delayed Chemotherapy Initiation after Cytoreductive Surgery for Advanced-Stage Ovarian Cancer: A Prospective Cohort Study.

Objective: The aim of this study was to evaluate factors associated with 30-day postoperative Clavien−Dindo classification (CDC) grade IIIa or greater complications and delayed initiation of chemotherapy after cytoreductive surgery (CRS) for primary advanced-stage epithelial ovarian cancer (AEOC). Methods: This was a prospective study involving 300 patients who underwent primary or interval CRS for AEOC between February 2018 and September 2020. Postoperative complications were graded according to the CDC. Logistic regression analysis was used to evaluate factors predicting CDC grade ≥IIIa and time to chemotherapy (TTC) >42 days. Results: Interval CRS was performed in 255 (85%) patients. CDC grade ≥IIIa occurred in 51 (17%) patients. In multivariable analysis, age (p = 0.036), cardiovascular comorbidity (p < 0.001), diaphragmatic surgery (p < 0.001), intraoperative urinary tract injury (p = 0.017), and upper-abdominal visceral injury (e.g., pancreas, stomach, liver, or spleen) (p = 0.012) were associated with CDC grade ≥IIIa. In 26% of cases, TTC was >42 days (median (IQR) 39 (29−50) days) in patients with CDC grade ≥IIIa versus 33 (25−41) days in patients without CDC grade ≥ IIIa (p = 0.008). The adjusted odds ratio of developing TTC >42 days was significantly higher in patients associated with WHO performance grade ≥2 (p = 0.045), intraoperative bowel injury (p = 0.043), upper-abdominal visceral injury (p = 0.008), and postoperative CDC grade ≥IIIa (p = 0.032). Conclusions: Patients with advanced age, with cardiovascular comorbidity, and who required diaphragmatic surgery had an increased adjusted odds ratio of developing CDC grade ≥IIIa complications. CDC grade ≥IIIa complications were independently associated with TTC >42 days. Proper patient selection and prevention of intraoperative injury are essential in order to prevent postoperative complications and delayed initiation of chemotherapy.

Factors predicting postoperative morbidity after cytoreductive surgery for ovarian cancer: a systematic review and meta-analysis.

OBJECTIVE: Advances in ovarian cancer cytoreductive surgery have enabled more extensive procedures to achieve maximal cytoreduction but with a consequent increase in postoperative morbidity and mortality. The aim of this study was to evaluate factors for postoperative morbidity after extensive cytoreductive surgery for primary epithelial ovarian cancer (EOC), particularly those which may be modifiable. METHODS: Electronic databases were searched. Meta-analysis was conducted using random-effects models. RESULTS: Fifteen relevant studies, involving 15,325 ovarian cancer patients, were included in this review. Severe 30-day postoperative complications occurred in 2,357 (15.4%) patients. The postoperative mortality rate was 1.92%. Meta-analysis demonstrated that patient with following risk factors; age (p<0.001), Eastern Cooperative Oncology Group score >0 (p=0.001), albumin level <3.5 g/dL (p<0.001), presence of ascites on CT scan (p=0.013), stage IV disease (p<0.001) and extensive surgical procedure (p<0.001) has a significantly increase risk of developing postoperative complications. Surgical procedures including peritonectomy (p=0.012), splenectomy (p<0.001) and colon surgery (p<0.001) were significant predictors for postoperative complications. Moreover, we found that patients who received neoadjuvant chemotherapy followed by interval debulking surgery (NACT-IDS) had a lower risk of developing severe complications compared to those who underwent primary debulking surgery (PDS) (p<0.001). CONCLUSION: Our study demonstrated that patient performance status and hypoalbuminemia were the only significant adjustable preoperative risk factors associated with postoperative complications. Patients who underwent NACT-IDS had a lower risk of developing severe complications compared to PDS. TRIAL REGISTRATION: International Prospective Register of Systematic Reviews (PROSPERO) Identifier: CRD42021282770.