Is routine admission to a critical care setting following hyperthermic intraperitoneal chemotherapy for ovarian cancer necessary?

INTRODUCTION: Hyperthermic intraperitoneal chemotherapy (HIPEC) is increasingly being used in patients with stage III ovarian cancer undergoing interval cytoreductive surgery (CRS). It is uncertain whether routine postoperative admission to a critical care setting after CRS-HIPEC is necessary. This study aims to estimate the incidence of patients requiring critical care, and to create a prediction model to identify patients who may forego admission to a critical care setting. METHODS: We analyzed 154 patients with primary ovarian cancer undergoing interval CRS-HIPEC at two Dutch centers between 2007 and 2021. Patients were routinely admitted to a critical care setting for 12-24 h. Patients that received critical support as defined by pre-specified definitions were retrospectively identified. Logistic regression analysis with backward selection was used to predict the need for critical care and the model was validated using bootstrapping. RESULTS: Thirty-eight percent of patients received postoperative critical care, consisting mainly of hemodynamic interventions. Independent predictors of critical care were blood loss, norepinephrine dose during surgery, and age (bootstrapped AUC = 0.76). Using a probability cut-off of 20%, one-third of patients are defined as low-risk for requiring critical care, with a negative predictive value of 0.88. CONCLUSIONS: The majority of patients,primarily undergoing low to intermediate complexity surgeries, did not receive critical care interventions after CRS-HIPEC. Selective admission to a critical care setting may be warranted and its feasibility and safety needs to be evaluated prospectively. Our prediction model can help identify patients in whom admission to a critical care setting may be omitted. Hospital costs and burden on critical care units will benefit from patient selection.

Cytoreductive surgery with or without hyperthermic intraperitoneal chemotherapy in patients with advanced ovarian cancer (OVHIPEC-1): final survival analysis of a randomised, controlled, phase 3 trial.

BACKGROUND: The OVHIPEC-1 trial previously showed that the addition of hyperthermic intraperitoneal chemotherapy (HIPEC) to interval cytoreductive surgery resulted in improved progression-free and overall survival compared with cytoreductive surgery alone at 4·7 years of follow-up in patients with stage III epithelial ovarian cancer who were ineligible for primary cytoreduction. We report the final survival outcomes after 10 years of follow-up. METHODS: In this open-label, randomised, controlled, phase 3 trial, patients with primary epithelial stage III ovarian cancer were recruited at eight HIPEC centres in the Netherlands and Belgium. Patients were eligible if they were aged 18-76 years, had not progressed during at least three cycles of neoadjuvant carboplatin plus paclitaxel, had a WHO performance status score of 0-2, normal blood counts, and adequate renal function. Patients were randomly assigned (1:1) to undergo interval cytoreductive surgery without HIPEC (surgery group) or with HIPEC (100 mg/m2 cisplatin; surgery-plus-HIPEC group). Randomisation was done centrally by minimisation with a masked web-based allocation procedure at the time of surgery when residual disease smaller than 10 mm diameter was anticipated, and was stratified by institution, previous suboptimal cytoreductive surgery, and number of abdominal regions involved. The primary endpoint was progression-free survival and a secondary endpoint was overall survival, analysed in the intention-to-treat population (ie, all randomly assigned patients). This study is registered with ClinicalTrials.gov, NCT00426257, and is closed. FINDINGS: Between April 1, 2007, and April 30, 2016, 245 patients were enrolled and followed up for a median of 10·1 years (95% CI 8·4-12·9) in the surgery group (n=123) and 10·4 years (95% CI 9·5-13·3) in the surgery-plus-HIPEC group (n=122). Recurrence, progression, or death occurred in 114 (93%) patients in the surgery group (median progression-free survival 10·7 months [95% CI 9·6-12·0]) and 109 (89%) patients in the surgery-plus-HIPEC group (14·3 months [12·0-18·5]; hazard ratio [HR] 0·63 [95% CI 0·48-0·83], stratified log-rank p=0·0008). Death occurred in 108 (88%) patients in the surgery group (median overall survival 33·3 months [95% CI 29·0-39·1]) and 100 (82%) patients in the surgery-plus-HIPEC group (44·9 months [95% CI 38·6-55·1]; HR 0·70 [95% CI 0·53-0·92], stratified log-rank p=0·011). INTERPRETATION: These updated survival results confirm the long-term survival benefit of HIPEC in patients with primary stage III epithelial ovarian cancer undergoing interval cytoreductive surgery. FUNDING: Dutch Cancer Foundation (KWF Kankerbestrijding).

Translational and pharmacological principles of hyperthermic intraperitoneal chemotherapy for ovarian cancer.

The long-term survival of advanced-stage ovarian cancer patients remains poor, despite extensive cytoreductive surgery, chemotherapy, and the recent addition of poly (ADP-ribose) polymerase inhibitors (PARPi). Hyperthermic intraperitoneal chemotherapy (HIPEC) has shown survival benefit by specifically targeting peritoneal metastases, the primary site of disease recurrence. Different aspects of how HIPEC exerts its effect remain poorly understood. Improved understanding of the effects of hyperthermia on ovarian cancer cells, the synergy of hyperthermia with intraperitoneal chemotherapy, and the pharmacological and pharmacokinetic properties of intraperitoneally administered cisplatin may help identify ways to optimize the efficacy of HIPEC. This review provides an overview of these translational and pharmacological principles of HIPEC and aims to expose knowledge gaps that may direct further research to optimize the HIPEC procedure and ultimately improve survival for women with advanced ovarian cancer.

Large primary vaginal stone in a woman with multiple sclerosis.

Vaginal stones are rare and therefore a delay in accurate diagnosis often occurs. We present a 54-year old woman with multiple sclerosis who was diagnosed with a primary vaginal stone. Initially, she presented with recurring urinary tract infections (UTI) and macroscopic haematuria to the urologist. A cystoscopy showed no abnormalities. Because of persistent bleeding, she was referred to the gynaecologist, and on gynaecological examination, a vaginal stone was revealed. Stone formation was likely to be the result of urinary pooling due to incontinence, which was caused by a neurogenic bladder. Other contributing factors were prolonged recumbency, threads of an intrauterine device and a UTI. The presence of a vesicovaginal fistula was excluded by testing with methylene blue. The stone was surgically removed and composed of 70% struvite and 30% apatite. The patient was treated for decubitus ulcerations of the vaginal wall with estriol (Synapause-E3). Follow-up was uneventful.