Comparison of total and endometrial circulating cell-free DNA in women with and without endometriosis.

RESEARCH QUESTION: Do women with laparoscopically confirmed endometriosis have higher plasma concentrations of circulating cell-free DNA (cirDNA) than those without endometriosis? DESIGN: Prospective study of women aged 18-45 years undergoing benign gynaecological laparoscopy at two tertiary hospitals. Venous blood was collected immediately before surgery, and women were allocated to the endometriosis or control groups based on surgical findings. Total plasma cirDNA and cirDNA integrity were measured by quantitative polymerase chain reaction (qPCR) targeting short (115 bases) and long (247 bases) ALU segments. Endometrial-derived cirDNA was measured by qPCR of bisulfite-treated cirDNA using primers selective for a FAM101A sequence uniquely unmethylated in endometrial tissue. Five cirDNA parameters were compared between the control and endometriosis cohorts: total cirDNA concentration, long-stranded cirDNA concentration, integrity ratio, endometrial cirDNA concentration and endometrial cirDNA proportion. RESULTS: Twenty-eight endometriosis and 15 control samples were included. Women with and without endometriosis had cirDNA concentrations of 2.24 ± 0.89 ng/ml and 2.56 ± 0.92 ng/ml, respectively. Analysis by phenotype of endometriosis revealed a significantly higher endometrial cirDNA concentration in women with superficial disease (n = 10) compared with deep endometriosis (n = 18) (mean difference 0.14 ng/ml; 95% CI 0.15 to 0.26; P = 0.025), but not with controls. CONCLUSIONS: No significant differences were found in any of the cirDNA parameters between women with and without endometriosis. The low statistical power and heterogenous pelvic pathology in the control group render it difficult to determine whether the negative results reflect a true lack of increase in cirDNA in endometriosis.

A Double-blinded, Randomized, Placebo-controlled Trial of Antibiotic Prophylaxis in Elective Non-hysterectomy Laparoscopic Surgery for Benign Gynecologic Conditions: A Pilot Study.

STUDY OBJECTIVE: To determine the feasibility of a double-blinded randomized, placebo-controlled study in determining the efficacy of antibiotic prophylaxis in preventing postoperative infections (POIs) in elective nonhysterectomy laparoscopic procedures for benign gynecologic conditions. DESIGN: Double-blinded, randomized, placebo-controlled trial. SETTING: University-affiliated tertiary referral hospital in Sydney, Australia. PATIENTS: Women older than 18 years undergoing elective nonhysterectomy laparoscopic procedures for benign gynecologic conditions were eligible for the study and approached. INTERVENTIONS: Before surgery, participants were randomized to receive either 2-g cephazolin or placebo (10-mL normal saline) administered by the anesthetist. Participants and other research staff were blinded to group allocation. MEASUREMENTS AND MAIN RESULTS: The primary outcome was study feasibility measured by recruitment rates, compliance rates of drug administration, compliance rates of delivery, maintenance of double blinding, and follow-up rates. Secondary outcomes included rate of POIs, length of hospitalization, readmission to hospital, unscheduled presentations to healthcare facilities, and antibiotic-related reactions. Between February 2019 and March 2021, 170 patients were approached with 117 participants (68.8%) recruited and randomized. The study had a high compliance rate of trial drug delivery (95.7%) and a high follow-up rate (99.1%). CONCLUSION: This pilot study has demonstrated feasibility of a large-scale study with a recruitment rate of 68% of patients approached and excellent trial drug delivery and follow-up rates. As anticipated, it is underpowered for identifying clinically significant findings for POI rates. A large-scale study is appropriate and essential to determine the health-related risks of antibiotic prophylaxis with an emphasis on antimicrobial stewardship. The sample size for a large-scale study is 1678 participants based on infection rates in this pilot study.

A review of gynaecological surgical practices for trainees and certified specialists in Australia by volume using MBS and AIHW databases.

BACKGROUND: There is a finite volume of surgery performed annually by trainees and certified specialists alike. The detailed assessment of this surgical substrate is important, since it guides true exposure in gynaecological surgical training and practice after fellowship. AIMS: This study quantifies the volume and profile of major gynaecological surgical procedures performed in Australia within a specified five-year period and discusses the implications for training and practice. MATERIALS AND METHODS: Australian Institute of Health and Welfare data were examined to quantify the total number of major gynaecological procedures performed between 2013 and 2018. Medicare data were analysed to quantify the number of billed procedures. These data were compared with published Australian RANZCOG trainees and operative gynaecologists, to estimate the potential annual average exposure for each procedure. RESULTS: Major open, laparoscopic and vaginal surgeries constitute less than 27% of the 600 000 gynaecological procedures performed annually in Australia. Most major gynaecological surgeries are performed at rates lower than 12 cases per year for both trainees and specialists. Over the study period, laparotomies, vaginal hysterectomies and continence procedures decreased, and operative laparoscopies and laparoscopic hysterectomies increased. CONCLUSIONS: The volume of available major gynaecological procedures in Australia may not allow sufficient exposure for optimal training and practice for all trainees and specialists in operative gynaecology. This shortfall may compromise the ability to obtain and maintain proficiency in some core gynaecological operative procedures.

Gynaecological and IVF procedures billed through the Medicare Benefits Schedule (MBS) during the COVID-19 pandemic.

BACKGROUND: In response to the COVID-19 pandemic in Australia, restrictions to elective surgeries were implemented nationwide. AIMS: To investigate the response to these restrictions in elective gynaecological and In vitro fertilisation (IVF) procedures during the first wave of the COVID-19 pandemic. MATERIALS AND METHODS: We analysed the Medicare Item Reports for the number of elective gynaecological (labioplasty, vulvoplasty; prolapse and continence; operative hysteroscopy; hysterectomy; fertility) and IVF procedures claimed in Australia between January-June 2020 and compared these to January-June 2019. RESULTS: The number of included gynaecological and IVF procedures performed in January-June 2020 decreased by -13.71% and -12.56%, respectively, compared to January-June 2019. The greatest reductions were in May 2020 (gynaecology -43.71%; IVF -51.63% compared to May 2019), while April 2020 reported decreases of -37.69% and -31.42% in gynaecological and IVF procedures, respectively. In April 2020, 1963 IVF cycle initiations (-45.20% compared to April 2019), 2453 oocyte retrievals (-26.99%) and 3136 embryo transfers (-22.95%) were billed. The procedures with greatest paired monthly decrease were prolapse and continence surgeries in April (676 procedures; -51.85%) and May 2020 (704 procedures; -60.05%), and oocyte retrievals in May 2020 (1637 procedures; -56.70%). CONCLUSIONS: While we observed a decrease in procedural volumes, elective gynaecological and IVF procedures continued in considerable numbers during the restricted timeframes. In the event of future overwhelming biological threat, careful consideration must be given to more effective measures of limiting access for non-emergency procedures to conserve essential resources and reduce risk to both the public and healthcare staff.

Sodium thiosulfate during cisplatin-based hyperthermic intraperitoneal chemotherapy is associated with transient hypernatraemia without clinical sequelae.

Objectives: Cisplatin is commonly used during intraperitoneal chemotherapy however has well-established nephrotoxic side-effects. Sodium thiosulfate is often added to cisplatin-based hyperthermic intraperitoneal chemotherapy (HIPEC) protocols to mitigate this, however evidence regarding risk of hypernatraemia is scarce as of yet. Methods: We retrospectively identified patients undergoing cytoreductive surgery (CRS) for peritoneal surface malignancies of any origin at a single high-volume unit between April 2018 and December 2020. Patients were included if they received cisplatin-based HIPEC with intravenous sodium thiosulfate. Blood tests were collected pre-surgery and then daily during admission. Hypernatraemia was defined as serum sodium >145 mmol/L. Renal impairment was defined using the RIFLE criteria. Results: Eleven CRSs met inclusion criteria, the majority of which were indicated for ovarian cancer (72.7%). One (9.1%) patient with mesothelioma received mitomycin C as an additional chemotherapy agent. The incidence of hypernatraemia was 100% but all cases were transient, with no clinical sequelae observed. The rate of AKI was 36.4%, with three (27.3%) patients classified as risk and one (9.1%) instance of failure. No long-term renal impairment was observed. Conclusions: Despite biochemical evidence of mild hypernatraemia but with the absence of clinical sequelae, sodium thiosulfate appears to be safe when used in adjunct to cisplatin-based HIPEC during CRS. These findings should be evaluated with further comparative studies. When describing renal impairment, it is important that standardisation in reporting occurs, with the RIFLE and Acute Kidney Injury Network criteria now the preferred consensus definitions.

Risk factors and clinical outcomes in patients undergoing cytoreductive surgery with concomitant ureteric reimplantation.

OBJECTIVES: There are currently scarce data exploring ureteric reimplantation (UR) during cytoreductive surgery (CRS). METHODS: We identified patients undergoing CRS for peritoneal surface malignancies (PSM) of any origin at a single high-volume unit. UR was defined as ureteroureterostomy, transureterouretostomy, ureteroneocystostomy, ureterosigmoidostomy or ileal conduit performed during CRS. Peri-operative outcomes, long-term survival and risk factors for requiring UR were analysed. RESULTS: Seven hundred and sixty-seven CRSs were identified. Twenty-three (3.0%) procedures involved UR. Bladder resection and colorectal cancer (CRC) were associated with increased risk of UR (bladder resection: OR 12.90, 95% CI 4.91-33.90, p<0.001; CRC: OR 2.51, 95% CI 1.05-6.01, p=0.038). UR did not increase the risk of Grade III-IV morbidity or mortality. The rate of ureteric leak was 3/23 (13.0%) in the UR group. Mean survival was equivocal in patients with CRC (58.14 vs. 34.25 months, p=0.441) but significantly lower in those with high-grade appendiceal mucinous neoplasm (HAMN) undergoing UR (73.98 vs. 30.90 months, p=0.029). CONCLUSIONS: UR during CRS does not increase major morbidity or mortality for carefully selected patients, and is associated with low rates of urologic complications. Whilst decreased survival was apparent in patients with HAMN undergoing UR, it is unclear whether this relationship is causal.