Gregg Nelson

Mode of Minimally Invasive Surgery Associated with Venous Thromboembolism Incidence in Gynecologic Cancer Patients

Postoperative venous thromboembolism (VTE) after minimally invasive surgery (MIS) for gynecologic malignancy is uncommon. Our objective was to characterize the rates and identify risk factors of postoperative VTE. A retrospective cohort study of patients undergoing MIS for gynecologic malignancy at three Canadian institutions from 2014 to 2020 was performed. The primary outcome was incidence of VTE within 90 days post-operatively. Descriptive statistics were used for clinicopathologic factors, and univariate analysis compared differences between groups. Rate and 95% confidence interval for VTE per 1000 surgeries were calculated. A total of 1786 patients met inclusion criteria, 85.3% uterine, 11.5% cervical, and 2.3% had ovarian cancer. Modes of surgery included robotic (49.4%), laparoscopic (20.7%), or combined laparoscopic/vaginal (29.9%). There were 15 VTE events at 90 days post-operatively (0.84%). Rates of VTE were lowest in patients who underwent robotic surgery, followed by combined laparoscopic/vaginal, and highest in a laparoscopic approach (p = 0.047). Pelvic lymphadenectomy (p = 0.038) and adjuvant chemotherapy (p = 0.022) were the only significant factors associated with risk of VTE. The incidence of VTE after MIS for gynecologic malignancy is low. Robotic surgery was associated with a lower incidence, although event rates are low, and further research is warranted.

Risk factors for second primary cancer in a prospective cohort of endometrial cancer survivors: an Alberta Endometrial Cancer Cohort Study

Abstract We examined associations between modifiable and nonmodifiable cancer-related risk factors measured at endometrial cancer diagnosis and during early survivorship (~3 years postdiagnosis) with second primary cancer (SPC) risk among 533 endometrial cancer survivors in the Alberta Endometrial Cancer Cohort using Fine and Gray subdistribution hazard models. During a median follow-up of 16.7 years (IQR, 12.2-17.9), 89 (17%) participants developed an SPC; breast (29%), colorectal (13%), and lung (12%) cancers were the most common. Dietary glycemic load before endometrial cancer diagnosis (≥90.4 vs < 90.4 g/day: subhazard ratio [sHR] = 1.71; 95% CI, 1.09-2.69), as well as older age (≥60 vs < 60 years: sHR = 2.48; 95% CI, 1.34-4.62) and alcohol intake (≥2 drinks/week vs none: sHR = 3.81; 95% CI, 1.55-9.31) during early survivorship, were associated with increased SPC risk. Additionally, reductions in alcohol consumption from prediagnosis to early survivorship significantly reduced SPC risk (sHR = 0.34; 95% CI, 0.14-0.82). With 1 in 6 survivors developing an SPC, further investigation of SPC risk factors and targeted surveillance options for high-risk survivors could improve long-term health outcomes in this population. Reductions in dietary glycemic load and alcohol intake from prediagnosis to early survivorship showed promising risk reductions for SPCs and could be important modifiable risk factors to target among endometrial cancer survivors. This article is part of a Special Collection on Gynecological Cancer.

Cervical cancer screening outcomes among First Nations and non‐First Nations women in Alberta, Canada

Cervical cancer disproportionately affects First Nations women in Canada but there is limited information on their participation in organized cervical cancer screening programs. This co-led retrospective cohort study linked population-based Alberta Cervical Cancer Screening Program point of care data with First Nations identifiers. This Screening Program database includes cervical cancer screening history, screen test results, colposcopy procedure findings, and pathology results for all women in Alberta. First Nations identifiers were obtained from Alberta Health who steward these data on their behalf. Data were available from 2012 to 2018 for women 25 - 69 years of age who were age eligible to participate in cervical cancer screening. Screening participation and retention rates, and screening outcomes were compared between First Nations and non- First Nations women using descriptive statistics with trends estimated using joinpoint models. Age standardized screening participation and retention rates of First Nations women were lower than those for the non-First Nations women, with an average difference of 13.9 % lower for participation rates (95 % confidence interval = 12.9-14.8 %; P <.0001) and 7.2 % for retention rates (95 % confidence interval = 2.2 % to 12.72; P = 0.013). First Nations women consistently had higher percentages of high risk (high-grade squamous intraepithelial lesion, atypical glandular cells, atypical squamous cells where HSIL cannot be excluded, Carcinoma in situ) abnormal cytology tests than non-First Nations women. Identifying where inequities were found in cervical cancer screening participation and retention in this study is the first step to reduce the disproportionate burden of cervical cancer for First Nations women in Canada.

Concurrent RB1 Loss and BRCA Deficiency Predicts Enhanced Immunologic Response and Long-term Survival in Tubo-ovarian High-grade Serous Carcinoma

Abstract Purpose: The purpose of this study was to evaluate RB1 expression and survival across ovarian carcinoma histotypes and how co-occurrence of BRCA1 or BRCA2 (BRCA) alterations and RB1 loss influences survival in tubo-ovarian high-grade serous carcinoma (HGSC). Experimental Design: RB1 protein expression was classified by immunohistochemistry in ovarian carcinomas of 7,436 patients from the Ovarian Tumor Tissue Analysis consortium. We examined RB1 expression and germline BRCA status in a subset of 1,134 HGSC, and related genotype to overall survival (OS), tumor-infiltrating CD8+ lymphocytes, and transcriptomic subtypes. Using CRISPR-Cas9, we deleted RB1 in HGSC cells with and without BRCA1 alterations to model co-loss with treatment response. We performed whole-genome and transcriptome data analyses on 126 patients with primary HGSC to characterize tumors with concurrent BRCA deficiency and RB1 loss. Results: RB1 loss was associated with longer OS in HGSC but with poorer prognosis in endometrioid ovarian carcinoma. Patients with HGSC harboring both RB1 loss and pathogenic germline BRCA variants had superior OS compared with patients with either alteration alone, and their median OS was three times longer than those without pathogenic BRCA variants and retained RB1 expression (9.3 vs. 3.1 years). Enhanced sensitivity to cisplatin and paclitaxel was seen in BRCA1-altered cells with RB1 knockout. Combined RB1 loss and BRCA deficiency correlated with transcriptional markers of enhanced IFN response, cell-cycle deregulation, and reduced epithelial–mesenchymal transition. CD8+ lymphocytes were most prevalent in BRCA-deficient HGSC with co-loss of RB1. Conclusions: Co-occurrence of RB1 loss and BRCA deficiency was associated with exceptionally long survival in patients with HGSC, potentially due to better treatment response and immune stimulation.

Safety of vaginal surgery for early-stage cervical cancer: A retrospective multicenter cohort study.

Abdominal Radical hysterectomy (ARH) with pelvic lymph node assessment is considered the standard treatment for early-stage cervical cancer. Accepted routes have previously included laparoscopic or robotic approaches (LRH). Laparoscopy-assisted vaginal or vaginal radical hysterectomy (LVRH) are performed in some centers. The objective of this study is to compare surgical and oncological outcomes of LVRH, to laparoscopic and abdominal approaches. A retrospective multicenter analysis of consecutive cervical cancer cases who underwent a radical hysterectomy between 2007 and 2017 in eleven regional cancer centers across Canada. A comparison of patients stratified by surgical technique was undertaken. T-test, Wilcoxon rank-sum and chi-square were used to compare patient characteristics. Log-rank tests and Cox proportional hazards models were employed to compare recurrence and survival across surgical groups. A total of 1071 patients with cervical cancer stage IA1 with lymphovascular invasion to stage IIIC (FIGO 2018) <4 cm were identified. Postoperative complication rate was lowest for women undergoing LVRH (9.1 %, vs 18.3 % and 22.1 % for minimally invasive and open respectively). During follow up, 114 women recurred, and 70 women died. 5-year recurrence-free survival was 85.4 % for LRH, 89.4 % for ARH and 92.2 % for LVRH. LVRH was not found to be associated with a higher risk of recurrence or death than ARH on multivariable analysis (aHR for recurrence 0.62, CI 0.21-1.77; aHR for death 0.63, CI 0.14-2.77) CONCLUSION: In this retrospective study, vaginal or laparoscopy-assisted vaginal radical hysterectomy for cervical cancer was associated with favorable perioperative and oncological outcomes.

Feasibility of ERAS guidelines for cytoreductive surgery with or without hyperthermic intraperitoneal chemotherapy (CRS-HIPEC): An international multicenter study

Enhanced Recovery After Surgery (ERAS) protocols aim to optimize perioperative care and improve recovery after major surgery. While ERAS pathways are well established in several oncologic disciplines, their feasibility and consistency in the setting of cytoreductive surgery, with or without hyperthermic intraperitoneal chemotherapy (CRS ± HIPEC), remain uncertain due to the complexity and heterogeneity of these procedures. A prospective multicenter observational study was conducted across 10 expert CRS-HIPEC centers to assess the feasibility and real-world implementation of the ERAS Society guidelines for cytoreductive surgery, with or without hyperthermic intraperitoneal chemotherapy. Perioperative practices were compared before (PRE-ERAS) and after (POST-ERAS) structured ERAS guideline implementation. ERAS adherence, clinical outcomes, and predictors of 90-day postoperative complications and prolonged length of stay were analyzed using multivariable logistic regression models. In addition, a predefined subgroup analysis compared outcomes between ovarian and non-ovarian primary tumors. Between 2021 and 2022, 497 patients were included (PRE-ERAS: 288; POST-ERAS: 209). Baseline characteristics were similar except for more ovarian primaries in POST-ERAS (26.4% vs 44%, p = 0.004). POST-ERAS patients showed higher adherence to anemia screening (60% vs 69%, p = 0.042), carbohydrate loading (4% vs 30%, p 70% ERAS adherence (OR 0.19, 95% CI 0.06-0.54, p = 0.003) predicted fewer complications. Ovarian primary (OR 0.50, 95% CI 0.28-0.87, p = 0.016), >70% adherence (OR 0.33, 95% CI 0.12-0.82, p = 0.025), and POST-ERAS status (OR 0.61, 95% CI 0.37-0.99, p = 0.046) correlated with shorter LOS. ERAS implementation for CRS ± HIPEC shortened hospital stay but remained incomplete and was associated with increased readmissions, without reducing complication rates. These findings highlight the need to focus on a pragmatic set of high-impact ERAS elements to improve feasibility in complex cytoreductive surgery.