Hyperthermic intraperitoneal chemotherapy (HIPEC) is increasingly recognized as an effective addition to cytoreductive surgery in advanced ovarian cancer, particularly in patients who respond to platinum-based chemotherapy.A systematic review of phase III randomized controlled trials testing the role of HIPEC in ovarian cancer was performed, according to the PRISMA guidelines.Seven randomized controlled trials were included. Data of 1252 patients with ovarian cancer were examined: 630 and 622 having surgery plus HIPEC and surgery alone, respectively. This review critically evaluates the role of HIPEC in various clinical scenarios, including primary and interval debulking surgery and secondary cytoreduction. Evidence from key clinical trials is summarized, focusing on its effects on progression-free and overall survival. Important factors such as patient selection, chemotherapy regimens, technical procedures, and perioperative care are examined. Potential side effects (including renal toxicity, gastrointestinal injury, and delayed recovery) are discussed. The review also assesses cost-effectiveness and integration of HIPEC into multidisciplinary treatment plans. Emerging approaches, such as combining HIPEC with targeted therapies and personalized treatment strategies, are explored.While HIPEC offers a promising therapeutic advance, further high-quality studies are needed to refine its use and assess its role in earlier stages of disease. This review aims to inform clinical decisions and support future research in the evolving management of ovarian cancer.Copyright © 2025 Elsevier Inc. All rights reserved.

Peritoneal metastases (PM), frequently observed in malignancies such as ovarian, colorectal, pancreatic, and gastric cancers, present a significant therapeutic challenge due to poor prognosis and limited effectiveness to systemic chemotherapy. The peritoneal-plasma barrier reduces effective drug transfer from plasma to the peritoneal cavity, reducing cytotoxic effects on PM. Intraperitoneal (IP) chemotherapy offers a locoregional approach, enabling high local drug concentrations that can enhance therapeutic efficacy while limiting systemic toxicity. The three major methods for IP administration-hyperthermic intraperitoneal chemotherapy (HIPEC), pressurized intraperitoneal aerosol chemotherapy (PIPAC), and catheter-based IP (CBIP) chemotherapy-each provide unique pharmacokinetic (PK) advantages for PM treatment. This review provides a comprehensive update on the pharmacological rationale of IP chemotherapy, focusing on drug characteristics that support extended IP retention and effective tumor targeting. The effects of administration variables are discussed, highlighting their role in optimizing IP drug exposure. Additionally, recent PK data on commonly used drugs in IP therapy, including platinum-based agents, taxanes, and novel nanoparticle formulations, will be evaluated. While PK rationale supports the administration of IP chemotherapy, further efficacy results from ongoing clinical trials are still awaited. Innovations in nanoparticle-based formulations and controlled-release systems offer substantial potential for improving both drug retention and targeted delivery, enhancing treatment precision and minimizing systemic toxicity. Continued exploration in these areas, along with optimization of IP administration protocols, is vital for advancing patient outcomes, refining therapeutic strategies, and maximizing the benefits of IP chemotherapy in clinical practice.© 2025. The Author(s).

Ovarian cancer is the leading cause of death among gynecological malignancies [...]

In 2024, two randomized controlled trials (RCTs) were published, providing new high-quality evidence on HIPEC in epithelial ovarian cancer (EOC). Updating data on progression-free survival (PFS) and adverse events could offer a clearer understanding of the benefits and risks of HIPEC combined with cytoreductive surgery (CRS), with or without prior neoadjuvant chemotherapy (NACT).An electronic search was conducted using PubMed, Web of Science, EBSCO, and CENTRAL up to 23 November 2024. We only included RCTs reporting PFS and adverse events of interval or secondary CRS, with or without HIPEC, in newly diagnosed or recurrent EOC.The meta-analysis included six RCTs. The addition of HIPEC to surgery significantly improved PFS in patients with newly diagnosed advanced-stage EOC who received NACT (HR 0.59; 95% CI 0.39-0.88; p = 0.01). No significant difference in PFS was observed between secondary CRS plus HIPEC and CRS alone in recurrent ovarian cancer without prior NACT (HR 1.22; 95% CI 0.82-1.83; p = 0.32). Regarding adverse events, a decrease in platelet count of any grade was more frequent in the HIPEC group (p = 0.03). The overall risk of acute kidney failure (AKF) was 10.6%, with a significantly higher incidence compared with CRS alone (p = 0.003).The addition of HIPEC to CRS significantly improved PFS compared with surgery alone in patients with advanced EOC who received NACT. However, the treatment was associated with a higher incidence of AKF, which occurred in 10.6% of patients who underwent HIPEC.© 2025. The Author(s).

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.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/m 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.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).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.Dutch Cancer Foundation (KWF Kankerbestrijding).Copyright © 2023 Elsevier Ltd. All rights reserved.

Emerging evidence suggests that hyperthermic intraperitoneal chemotherapy (HIPEC) with cytoreductive surgery (CRS) shows a survival benefit over CRS alone for patients with epithelial ovarian carcinoma (EOC). This systematic review and meta-analysis will assess the safety and efficacy of HIPEC with CRS for EOC.Searches of five databases from inception to 17/02/15 was performed. Clinical outcomes were synthesised, with full tabulation of results.A total of 9 comparative studies and 28 studies examining HIPEC + CRS for primary and/or recurrent EOC were included. Meta-analysis of the comparative studies showed HIPEC + CRS + chemotherapy had significantly better 1-year survival compared with CRS + chemotherapy alone (OR: 3.76, 95% CI 1.81-7.82). The benefit of HIPEC + CRS continued for 2-, 3-, 4-, 5- and 8-year survival compared to CRS alone (OR: 2.76, 95% CI 1.71-4.26; OR: 5.04, 95% CI 3.24-7.85; OR: 3.51, 95% CI 2.00-6.17; OR: 3.46 95% CI 2.19-5.48; OR: 2.42, 95% 1.38-4.24, respectively). Morbidity and mortality rates were similar. Pooled analysis of all studies showed that among patients with primary EOC, the median, 1-, 3-, and 5-year overall survival rates are 46.1 months, 88.2%, 62.7% and 51%. For recurrent EOC, the median, 1-, 3-, and 5-year overall survival rates are 34.9 months, 88.6%, 64.8% and 46.3%. A step-wise positive correlation between completeness of cytoreduction and survival was found.The addition of HIPEC to CRS and chemotherapy improves overall survival rates for both primary and recurrent EOC.Copyright © 2015 Elsevier Ltd. All rights reserved.

The current treatment of ovarian cancer consists of cytoreductive surgery (CRS) and systemic chemotherapy. The aim of this study was to examine if hyperthermic intraperitoneal chemotherapy (HIPEC) is an alternative modality to treat this category of patients along with a second attempt of surgical resection and second- or third-line systemic chemotherapy afterward.In an 8-year period (2006-2013), 120 women with advanced ovarian cancer (International Federation of Gynecology and Obstetrics [FIGO] IIIc and IV) who experienced disease recurrence after initial treatment with conservative or debulking surgery and systemic chemotherapy were randomized into two groups. Group A comprised 60 patients treated with CRS followed by HIPEC and then systemic chemotherapy. Group B comprised 60 patients treated with CRS only and systemic chemotherapy.The mean survival for group A was 26.7 versus 13.4 months in group B (p < 0.006). Three-year survival was 75 % for group A versus 18 % for group B (p < 0.01). In the HIPEC group, the mean survival was not different between patients with platinum-resistant disease versus platinum-sensitive disease (26.6 vs. 26.8 months). On the other hand, in the non-HIPEC group, there was a statistically significant difference between platinum-sensitive versus platinum-resistant disease (15.2 vs. 10.2 months, p < 0.002). Complete cytoreduction was associated with longer survival. Patients with a peritoneal cancer index score of <15 appeared also to have longer survival.The use of HIPEC along with the extent of the disease and the extent of cytoreduction play an important role in the survival of patients with recurrence in an initially advanced ovarian cancer.

Epithelial ovarian carcinoma is the main cause of death from gynaecological cancers in the western world. The initial response rate to the frontline therapy is high. However, the prognosis of persistent and recurrent disease remains poor. During the two past decades, a new therapeutic approach to peritoneal carcinomatosis has been developed, combining maximal cytoreductive effort with hyperthermic intraperitoneal chemotherapy (HIPEC).A retrospective, multicentric study of 246 patients with recurrent or persistent ovarian cancer, treated by cytoreductive surgery and HIPEC in two French centers between 1991 and 2008, was performed.An optimal cytoreductive surgery was possible in 92.2 % of patients. Mortality and morbidity rates were 0.37 % and 11.6 %, respectively. The overall median survival was 48.9 months. There was no significant difference in overall survival in patients with persistent or recurrent disease. In multivariate analysis, performance status was a significant prognostic factor in patients with extensive peritoneal carcinomatosis (peritoneal cancer index >10).Salvage therapy combining optimal cytoreductive surgery and HIPEC is feasible and may achieve long-term survival in highly selected patients with recurrent ovarian carcinoma, including those with platinum resistant disease, with acceptable morbidity.

Women 65 years of age or older with epithelial ovarian cancer (EOC) are thought to have a worse prognosis than younger patients. However, no consensus exists concerning the best treatment for ovarian cancer in this age group. This report presents outcomes for patients treated with cytoreductive surgery (CRS) plus hyperthermic intraperitoneal chemotherapy (HIPEC).A prospective database of EOC patients treated with CRS/HIPEC (1998-2019) was analyzed. Perioperative variables were compared by treatment including upfront CRS/HIPEC, neoadjuvant chemotherapy plus CRS/HIPEC (NACT + CRS/HIPEC), and salvage CRS/HIPEC, and by age at surgery (< 65 and ≥ 65 years). Survival analysis was performed, and outcomes were compared.Of the 148 patients identified, 42 received upfront CRS/HIPEC, 48 received NACT + CRS/HIPEC, and 58 received salvage CRS/HIPEC. Each group was subdivided by age groups (< 65 and ≥ 65 years). The median overall survival (OS) after the upfront CRS/HIPEC was 69.2 months for the patients < 65 years of age versus 69.3 months for those ≥ 65 years of age. The OS after NACT + CRS/HIPEC was 26.9 months for the patients < 65 years of age versus 32.9 months for those ≥ 65 years of age, and the OS after salvage CRS/HIPEC was 45.6 months for the patients < 65 years of age versus 23.9 months for those ≥ 65 years of age. The median progression-free survival (PFS) after upfront CRS/HIPEC was 41.3 months for the patients < 65 years of age versus 45.4 months for those ≥ 65 years of age. The PFS after NACT + CRS/HIPEC was 16.2 months for the patients < 65 years of age versus 11.2 months for those ≥ 65 years of age, and the PFS after salvage CRS/HIPEC was 18.7 months for the patients < 65 years of age versus 10 months for those ≥ 65 years of age. The median follow-up period for the entire cohort was 44.6 months [95% confidence interval (CI) 34.7-60.6 months].Age and feasibility of complete cytoreduction should be considered when treatment methods are selected for elderly patients. A carefully selected elderly population can benefit significantly from aggressive treatment methods.

To evaluate the impact of frailty on postoperative complications following cytoreductive surgery (CRS) with hyperthermic intra-peritoneal chemotherapy (HIPEC) in women with advanced or recurrent gynecologic cancer.An IRB-approved single-institution prospective registry was queried for women who underwent CRS with HIPEC for advanced or recurrent gynecologic cancer from 1/1/2014-12/31/2020. Frailty was defined as a modified Frailty Index (mFI) score of ≥2. Logistic regression was used to assess the impact of mFI upon the rate of moderate or higher (≥ grade 2) Accordion postoperative complications.Of 141 women, 81.6% (n = 115) were non-frail with mFI of 0-1 and 18.4% (n = 26) were frail with mFI ≥2. The incidence of ≥ grade 2 complications was 21.2% (n = 14) for mFI = 0, 26.5% (n = 13) for mFI = 1, 64.7% (n = 11) for mFI = 2 and 100.0% (n = 9) for patients with mFI ≥3. The incidence of re-operation (1.7% vs. 11.5%, p = 0.044), ICU admission (13.2% vs. 34.6%, p = 0.018), acute kidney injury (6.3% vs. 30.8%, p = 0.001), and respiratory failure (0.9% vs. 19.2%, p < 0.001) were significantly lower amongst non-frail vs. frail women. On multivariable analysis, mFI ≥2 was associated with significantly increased ≥ grade 2 complications versus mFI of 0-1 (OR 9.4, 95% CI 3.3, 26.4, p < 0.001). Age (OR 1.04, 95% CI 1.00, 1.09, p = 0.07), surgical indication (recurrent vs. primary) (OR 0.71, 95% CI 0.30, 1.7, p = 0.44) and Surgical Complexity Score of Intermediate or High vs. Low (OR 1.5, 95% CI 0.67, 3.5, p = 0.31) were not associated with ≥grade 2 complications.Frailty, defined by the modified frailty index, is predictive of ≥grade 2 postoperative complications following CRS with HIPEC in women with gynecologic cancer. Frailty screening before CRS with HIPEC may assist patient selection and improve postoperative outcomes.Copyright © 2021. Published by Elsevier Inc.

The safety and efficacy of hyperthermic intrathoracic chemotherapy (HITHOC) as an adjunct to cytoreductive surgery (CRS) in pleural malignancies has been well demonstrated. This is most often described in cases of mesothelioma, thymoma, or other secondary pleural metastases. The utilization of a direct cytotoxic agent with increased penetration secondary to a hyperthermic environment is especially beneficial in pleural malignancy as a microscopic resection remains immensely challenging. Despite favorable outcomes with a limited associated risk profile, there persists a variety in utilization and technique of HITHOC described in current literature. National Comprehensive Cancer Network (NCCN) guidelines state that though intraoperative adjuvant therapies such as HITHOC have been studied, they remain of unclear benefit and definitive recommendations do not currently exist. This ambiguity limits the standardization of HITHOC, thus hindering its further application in a patient population with exceedingly poor outcomes within current guideline-based therapy. As the prevalence of pleural malignancies necessitating CRS with adjuvant HITHOC remains quite low, we believe a task force initiative to further investigate the role of HITHOC in surgical management of pleural malignancies would enable wider utility of this promising technique. Additionally, we propose that the creation of a pleural cancer index could aid in standardization of HITHOC in those with pleural malignancy.2023 Journal of Thoracic Disease. All rights reserved.

Safe implementation and thorough evaluation of new treatments require prospective data monitoring and standardization of treatments. Pressurized intraperitoneal aerosol chemotherapy (PIPAC) is a promising alternative for the treatment of patients with peritoneal disease with an increasing number of suggested drug regimens. The aim was to reach expert consensus on current PIPAC treatment protocols and to define the most important research topics.The expert panel included the most active PIPAC centers, organizers of PIPAC courses and principal investigators of prospective studies on PIPAC. A comprehensive literature review served as base for a two-day hybrid consensus meeting which was accompanied by a modified three-round Delphi process. Consensus bar was set at 70% for combined (strong and weak) positive or negative votes according to GRADE. Research questions were prioritized from 0 to 10 (highest importance).Twenty-two out of 26 invited experts completed the entire consensus process. Consensus was reached for 10/10 final questions. The combination of doxorubicin (2.1 mg/m) and cisplatin (10.5 mg/m) was endorsed by 20/22 experts (90.9%). 16/22 (72.7%) supported oxaliplatin at 120 with potential reduction to 90 mg/m (frail patients), and 77.2% suggested PIPAC-Ox in combination with 5-FU. Mitomycin-C and Nab-paclitaxel were favoured as alternative regimens. The most important research questions concerned PIPAC conditions (n=3), standard (n=4) and alternative regimens (n=5) and efficacy of PIPAC treatment (n=2); 8/14 were given a priority of ≥8/10.The current consensus should help to limit heterogeneity of treatment protocols but underlines the utmost importance of further research.© 2022 Olivia Sgarbura et al., published by De Gruyter, Berlin/Boston.

\n Recurrent, platin-resistant ovarian cancer (rPROC) has a poor survival. Even with the AURELIA trial, which is the best available treatment today, progression-free survival (PFS) is still only 6.7 months from the start of the second-line chemotherapy. Innovative, effective therapies are urgently needed. Pressurized Intra-Peritoneal Aerosol Chemotherapy (PIPAC) is a novel drug delivery system for administering drugs into the abdomen. PIPAC with cisplatin and doxorubicin (PIPAC C/D) may be safely used at an intraperitoneal dose of 10.5 mg/m\n 2\n and 2.1 mg/m\n 2\n, respectively. Systemic toxicity of this therapy is low. In a phase II trial with 53 women, 62 % patients had an objective tumor response. Tumor regression on histology was observed in 76 % patients who underwent all three PIPACs. Randomized phase III studies are now required to evaluate the effect of PIPAC C/D compared to other standard treatments (sequential or simultaneous applications with systemic chemotherapy).\n

We aimed to investigate the therapeutic efficacy and safety of Pressurized IntraPeritoneal Aerosol Chemotherapy (PIPAC) in platinum-resistant recurrence of ovarian cancer and peritoneal carcinomatosis, while our secondary endpoint was to establish any changes in quality of life estimated via the EORTC QLQ-30 and QLQ-OV28 questionnaires.In this monocentric, single-arm, phase II trial, women were prospectively recruited and every 28-42 days underwent courses of PIPAC with doxorubicin 2.1 mg/m followed by cisplatin 10.5 mg/m via sequential laparoscopy.Overall, 98 PIPAC procedures were performed on 43 women from January 2016 to January 2020; three procedures were aborted due to extensive intra-abdominal adhesions. The clinical benefit rate (CBR) was reached in 82% of women. Three cycles of PIPAC were completed in 18 women (45%), and 13 (32.5%) and 9 (22.5%) patients were subjected to one and two cycles, respectively. During two PIPAC procedures, patients experienced an intraoperative intestinal perforation. There were no treatment-related deaths. Nineteen patients showed no response according to the Peritoneal Regression Grading Score (PRGS) and 8 patients showed minor response according to the PRGS. Median time from ovarian cancer relapse to disease progression was 12 months (95% confidence interval [CI] 6.483-17.517), while the median overall survival was 27 months (95% CI 20.337-33.663). The EORTC QLQ-28 and EORTC QLQ-30 scores did not worsen during therapy.PIPAC seems a feasible approach for the treatment of this subset of patients, without any impact on their quality of life. Since this study had a small sample size and a single-center design, future research is mandatory, such as its application in addition to systemic chemotherapy.© 2023. The Author(s).

\n Cytoreductive surgery (CRS) combined with hyperthermic intraperitoneal chemotherapy (HIPEC) is associated with improved survival in recurrent ovarian cancer (ROC) but carries a high risk of postoperative complications. Accurate perioperative risk stratification remains an unmet need. To develop and internally validate a perioperative risk model for postoperative complications in ROC patients using information available by the end of surgery (pre- and intra-operative data), and to compare logistic regression (LR) and artificial neural networks (ANN) as possible predictive models. A retrospective analysis of 71 patients treated with CRS and HIPEC between 2011 and 2022 was performed. Clinical, surgical, and perioperative variables were analysed. Predictors were restricted to variables available at or before the end of the index operation, which prevents information leakage by using only data available at prediction time. LR and ANN models were developed and assessed with cross-validation. Performance reporting followed TRIPOD (Type b) and TRIPOD + AI, with Brier score, and calibration slope/intercept from out‑of‑fold (OOF) predictions. Thresholded metrics (accuracy, precision, recall, F1 score, and the area under the receiver operating characteristic curve, AUC) were summarised at a prespecified probability cut-off. Exploratory univariate odds ratio analyses with Holm-adjusted p-values were used to explore procedure–complication associations. Postoperative complications occurred in 45% of patients. LR identified blood loss (\n p\n = 0.005) and number of procedures (\n p\n = 0.042) as significant predictors of complications. The LR model achieved an accuracy of 66.2%, precision of 64.3%, recall of 56.2%, F1 score of 60.0%, and AUC of 0.700. The ANN model achieved an accuracy of 97.2%, precision of 94.3%, recall of 100%, F1 score of 97.1%, and AUC of 0.967. Hysterectomy with adnexa (OR = 11.67,\n p\n = 0.035) and metastasectomy (OR = 7.42,\n p\n = 0.042) were significantly associated with higher postoperative complication rates. ANN demonstrated superior predictive performance compared to LR in identifying postoperative complications after CRS and HIPEC, as indicated by ROC analysis. Combining traditional statistical modelling with modern machine learning may enhance ROC for perioperative risk stratification after CRS with HIPEC. A well-calibrated, interpretable LR model together with a highly discriminative ANN could enable more tailored allocation of intensive care resources and earlier identification of high-risk patients, potentially improving the safety of this demanding but beneficial treatment. However, external multicentre validation is required before clinical implementation.\n

Acute kidney injury (AKI) following hyperthermic intraperitoneal chemotherapy (HIPEC) is common. Identifying patients at risk could have implications for surgical and anesthetic management. We aimed to develop a predictive model that could predict AKI based on patients' preoperative characteristics and intraperitoneal chemotherapy regimen. We retrospectively gathered data of adult patients undergoing HIPEC at our health system between November 2013 and April 2022. Next, we developed a model predicting postoperative AKI using multivariable logistic regression and calculated the performance of the model (area under the receiver operating characteristics curve [AUC]) via tenfold cross-validation. A total of 412 patients were included, of which 36 (8.7%) developed postoperative AKI. Based on our multivariable logistic regression model, multiple preoperative and intraoperative characteristics were associated with AKI. We included the total intraoperative cisplatin dose, body mass index, male sex, and preoperative hemoglobin level in the final model. The mean area under the receiver operating characteristics curve value was 0.82 (95% confidence interval 0.71-0.93). Our risk model predicted AKI with high accuracy in patients undergoing HIPEC in our institution. The external validity of our model should now be tested in independent and prospective patient cohorts.© 2024. The Author(s).

Hyperthermic intraperitoneal chemotherapy (HIPEC) with cisplatin confers a survival benefit in epithelial ovarian cancer (EOC) but is associated with renal toxicity. Sodium thiosulfate (ST) is used for nephroprotection for HIPEC with cisplatin, but standard HIPEC practices vary.

Hyperthermic intraperitoneal chemotherapy (HIPEC) is delivered after cytoreductive surgery (CRS) in selected patients with peritoneal carcinomatosis. The closed-abdomen technique, preferred by many centers, prevents heat loss and drug spillage, but does not warrant homogeneous distribution of the perfusion fluid (PF). The hypothesized formation of intra-abdominal adhesions during the closed-abdomen perfusion period has never been described.From March 2014 to April 2016, 10 consecutive patients with peritoneal carcinomatosis, selected for CRS, underwent the Laparoscopy-Enhanced HIPEC technique to explore the abdominal cavity during the perfusion. The aim of the study was to investigate the incidence and the extent of intra-abdominal adhesions that are formed after CRS during the perfusion period of closed-abdomen HIPEC.During the perfusion, adhesions developed in 70% of the patients. Adhesions developed mainly in the period between the closure of the abdomen and the subsequent filling of the abdomen with the PF. After their first division, during the following perfusion period, adhesions between the bowel and the abdominal wall reformed in 3 patients (30%).Intra-abdominal adhesions are frequently formed during closed-abdomen HIPEC and can hamper the adequate circulation of the PF. The Laparoscopy-Enhanced technique enables the early detection and the division of any intra-abdominal adhesions.

Small-bowel obstruction (SBO) after cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS/HIPEC) is a common complication associated with re-admission that may alter patients' outcomes. Our aim was to characterize and investigate the impact of bowel obstruction on patients' prognosis.This was a retrospective analysis of patients with SBO after CRS/HIPEC (n = 392). We analyzed patients' demographics, operative and perioperative details, SBO re-admission data, and long-term oncological outcomes.Out of 366 patients, 73 (19.9%) were re-admitted with SBO. The cause was adhesive in 42 (57.5%) and malignant (MBO) in 31 (42.5%). The median time to obstruction was 7.7 months (range, 0.5-60.9). Surgical intervention was required in 21/73 (28.7%) patients. Obstruction eventually resolved (spontaneous or by surgical intervention) in 56/73 (76.7%) patients. Univariant analysis identified intraperitoneal chemotherapy agents: mitomycin C (MMC) (HR 3.2, p = 0.003), cisplatin (HR 0.3, p = 0.03), and doxorubicin (HR 0.25, p = 0.018) to be associated with obstruction-free survival (OFS). Postoperative complications such as surgical site infection (SSI), (HR 2.2, p = 0.001) and collection (HR 2.07, p = 0.015) were associated with worse OFS. Multivariate analysis maintained MMC (HR 2.9, p = 0.006), SSI (HR 1.19, p = 0.001), and intra-abdominal collection (HR 2.19, p = 0.009) as independently associated with OFS. While disease-free survival was similar between the groups, overall survival (OS) was better in the non-obstruction group compared with the obstruction group (p = 0.03).SBO after CRS/HIPEC is common and complex in management. Although conservative management was successful in most patients, surgery was required more frequently in patients with MBO. Patients with SBO demonstrate decreased survival.© 2022. Society of Surgical Oncology.

Background: Encapsulating peritoneal sclerosis (EPS) is a rare surgical complication that can occur after intraperitoneal treatment. It is also a serious and potentially fatal complication of continuous ambulatory peritoneal dialysis. The present report describes a case of surgically treated EPS that probably occurred as a complication of hyperthermic intraperitonal chemotherapy (HIPEC). Case presentation: A 39-year-old man required sigmoidectomy for serosal invasive advanced sigmoid colon cancer. HIPEC with oxaliplatin, 5-fluorouracil and mitomycin C were given as adjuvant therapy. Subsequently, intestinal obstruction developed at 15 months postoperatively, and the patient was hospitalized. Abdominal computed tomography showed a dilated small intestine enveloped by a thickened membrane. We found no evidence of peritoneal recurrence, but exploratory surgery revealed EPS, probably caused by HIPEC. We peeled the capsule off of the intestine. The patient's postoperative course was uneventful, and sufficient nutritional intake after surgery was noted. Seven months after surgery, he is well with no recurrence. Conclusion: The surgical treatment via peritonectomy and enterolysis for postoperative EPS appears safe and effective. A diagnosis of EPS should be considered when intestinal obstruction does not show improvement with conservative treatment in patients who have undergone HIPEC, provided the possibility of peritoneal cancer recurrence is excluded.

Optimal cytoreductive surgery (CRS), followed by adjuvant chemotherapy, is a major predictor of oncological outcome in patients with advanced epithelial ovarian carcinoma (EOC). It is not clear if a delayed start of adjuvant chemotherapy negatively impacts on the oncological outcome.

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.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/m 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.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).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.Dutch Cancer Foundation (KWF Kankerbestrijding).Copyright © 2023 Elsevier Ltd. All rights reserved.

Imaging plays an integral role in the management of patients undergoing hyperthermic intraperitoneal chemotherapy, enabling accurate patient selection, estimation of the peritoneal carcinomatosis index and completeness of cytoreduction score, and evaluation of postprocedural complications.

To determine the effect of hyperthermic intraperitoneal chemotherapy (HIPEC) with carboplatin on the transcriptomic profiles of normal and ovarian cancer (OC) tissues.Normal and tumor samples from four OCs were prospectively collected pre- and immediately post-HIPEC treatment and subjected to RNA-sequencing. Differential gene expression, gene ontology enrichment and pathway analyses were performed. Heat shock protein and immune-response protein expression was assessed using protein arrays and western blotting.RNA-sequencing revealed 4231 and 322 genes significantly differentially expressed between pre- and post-treatment normal and OC tissues, respectively (both adjusted p-value <0.05). Gene enrichment analyses demonstrated that the most significantly upregulated genes in normal tissues played a role in immune as well as heat shock response (both adjusted p < 0.001). In contrast, HIPEC induced an increased expression of primarily heat shock response and protein folding-related genes in tumor tissues (both adjusted p < 0.001). HIPEC-induced heat shock protein (HSP) expression changes, including in HSP90, HSP40, HSP60, and HSP70, were also observed at the protein level in both normal and tumor tissues.HIPEC with carboplatin resulted in an upregulation of heat shock-related genes in both normal and tumor tissue, with an additional immune response gene induction in normal and protein folding in tumor tissue. The findings of our exploratory study provide evidence to suggest that HIPEC administration may suffice to induce gene expression changes in residual tumor cells and raises a biological basis for the consideration of combinatorial treatments with HSP inhibitors.Copyright © 2022 Elsevier Inc. All rights reserved.

To determine peri-operative outcomes in women with advanced epithelial ovarian cancer (EOC) undergoing interval debulking surgery (IDS) with hyperthermic intraperitoneal chemotherapy (HIPEC) via minimally invasive interval debulking surgery (MIS) or laparotomy (LAP).A single institution, retrospective cohort study was performed in women with EOC who underwent IDS with HIPEC from 2017 to 2019 via MIS or LAP. Peri-operative outcomes were compared using univariate analysis.In total, 50 eligible women were identified; ten (20.0%) underwent MIS + HIPEC and 40 (80.0%) LAP + HIPEC. The median age of patients in the MIS group was 71.1 vs. 64.2 years in LAP (p = 0.031). There was no significant difference in pre-operative complete radiographic response following NACT (p = 0.18). Notably, there was no difference in the rate of R0 resection (70.0% vs. 77.5%; p = 0.39). There was no significant difference in ICU admission, estimated blood loss, operative time, or use of vasopressors between the cohorts. Similarly, there was no difference in 30-day adverse events for MIS vs. LAP, but length of stay was decreased for those who underwent minimally invasive procedures (3 vs. 4 days, p = 0.016). Time to initiation of chemotherapy following surgery was not significantly different between groups (26.2 days vs 32.0 days, p = 0.090). With median follow-up of 15.1 months, there was no difference in recurrence free survival (median 15.0 vs 17.2 months log-rank, p = 0.30) for MIS vs. LAP.In this retrospective cohort study, we demonstrate that in women with advanced EOC, HIPEC with MIS at the time of IDS following NACT is feasible. Our institutional experience demonstrates similar rates of R0 cytoreduction, compared to LAP. An MIS approach should not prevent surgeons from utilizing HIPEC where indicated for management of advanced EOC.Copyright © 2020 Elsevier Inc. All rights reserved.