Christina Harlev

Pharmacokinetic comparison of cisplatin administration via HIPEC and intravenous infusion in a porcine model

Evaluating the risk of diaphragmatic hernia following left diaphragm resections during cytoreductive surgery for ovarian cancer: a Memorial Sloan Kettering Cancer Center Team Ovary study

To determine the incidence rate and risk factors associated with the development of diaphragm hernias following left diaphragm procedures at the time of ovarian cancer cytoreduction. We retrospectively reviewed data from patients diagnosed with epithelial ovarian, fallopian tube, or primary peritoneal carcinoma who underwent any timeframe of cytoreductive surgery (primary, interval, secondary, tertiary) at our institution from December 2010 to September 2024. Patients were included if they underwent left diaphragm peritonectomy or resection as part of their cytoreductive surgery. The diagnosis of left diaphragm hernia was made by computed tomography of the chest either as an incidental finding during follow-up surveillance or during work-up for symptomatology. We utilized statistical analysis with descriptive proportions with interquartile ranges. A total of 267 patients with ovarian cancer underwent a left diaphragm peritonectomy or resection as part of their cytoreductive surgery at our institution and were included in the study. The overall median age was 62 years (interquartile range; 52-70) and body mass index 24.9 kg/m Diaphragmatic hernias occurred most often following the setting of concurrent splenectomy; however, splenectomy was not a statistically significant risk factor. These findings provide meaningful insight into the frequency and clinical context in which this complication may arise, addressing a critical knowledge gap in the surgical management of patients with ovarian cancer who require upper abdominal and thoracic procedures.

The role of hyperthermia on abdominal tissue concentrations of cisplatin during and after intraperitoneal chemotherapy – insights from a porcine model

Epithelial ovarian cancer remains a leading cause of mortality among gynecological malignancies, with a high incidence of peritoneal carcinomatosis at diagnosis. Hyperthermic intraperitoneal chemotherapy (HIPEC) has emerged as a promising treatment for advanced-stage epithelial ovarian cancer, potentially improving recurrence-free and overall survival rates. The study aimed to investigate the impact of hyperthermia on cisplatin concentrations in healthy abdominal tissues by comparing HIPEC with normothermic intraperitoneal chemotherapy (NIPEC) in a novel porcine model. Sixteen cancer-free pigs underwent cytoreductive surgery followed by either HIPEC or NIPEC, with cisplatin administered intraperitoneally. Microdialysis was used to measure local cisplatin concentrations in various abdominal tissues over a 6-h period. The analysis revealed no statistically significant or clinically relevant difference in cisplatin concentrations between the HIPEC and NIPEC groups. In both groups, cisplatin concentrations were consistently higher in the peritoneum than in other tissues, and plasma levels were significantly lower than those in abdominal tissues. Hyperthermia did not enhance cisplatin's tissue penetration, suggesting that NIPEC may be an effective alternative to HIPEC, particularly for fragile and elderly patients. Future studies should investigate whether hyperthermia improves cisplatin delivery and cytotoxicity in tumor-infiltrated peritoneal tissues.

Dynamic Assessment of Local Abdominal Tissue Concentrations of Cisplatin During a HIPEC Procedure: Insights from a Porcine Model

Abstract Background This study aimed to establish a feasible large porcine model for dynamic assessment of cisplatin concentrations in carcinomatosis-relevant abdominal tissues using microdialysis during and after HIPEC combined with cytoreductive surgery. Methods In total, eight pigs underwent open abdominal cytoreductive surgery followed by HIPEC. Microdialysis was employed for dynamic cisplatin concentration sampling in abdominal organs and tissue. Cisplatin dialysate concentrations were analyzed using the UPLC-MS/MS method. STATA (version 18.0) was used to perform a two-compartment model with a zero-order distribution to analyze pharmacokinetic parameters. Results Detectable cisplatin concentrations in the evaluated target tissues persisted for at least 6 h post-HIPEC. Higher concentrations were found in superficial tissues; however, the difference was not statistically significant. The cisplatin concentrations were comparable for the stomach, rectum, and liver but higher in the peritoneal lining of the abdominal wall, with the lowest median average peak concentration (C max) in the rectum (0.50 µg/mL) and the highest median C max in the peritoneum (2.80 µg/mL). No statistically significant differences in cisplatin area under the curve from time zero to the time of the last sample collection (AUC0–last) were found between any of the abdominal compartments except the peritoneal lining of the abdominal wall, which was significantly higher compared with most of the other abdominal tissues {smallest difference; peritoneum 1/liver 2; 1.96 [95% confidence interval (CI) 0.90; 4.26, P = 0.09] and largest difference; peritoneum 3/rectum profound; 4.60 [95% CI 1.94; 10.90, P = 0.001]}. Conclusions Our investigation revealed comparable cisplatin concentrations across abdominal organ surfaces, except higher concentrations in the peritoneal lining of the abdominal wall than in the stomach, rectum, and liver. This model holds promise for future research into HIPEC interventions and anticancer effectiveness.

A prospective comparison of resectability scores to enhance preoperative decision-making in the primary management of advanced ovarian cancer: a Memorial Sloan Kettering Cancer Center Team Ovary study

To compare cytoreductive outcomes of 2 published algorithms used to triage patients with ovarian cancer to primary debulking surgery versus diagnostic laparoscopy or neoadjuvant chemotherapy. This prospective comparative study was conducted from August 1, 2021, to January 31, 2025. All patients with suspected advanced ovarian cancer who were eligible for primary debulking surgery on initial evaluation were identified. Imaging was reviewed utilizing a standardized radiology synoptic report. Data from the synoptic report were combined with clinical factors to determine a Resectability Score using 1 of 2 algorithms, Resectability Score 1.0 (RS1.0) and Resectability Score 2.0 (RS2.0). The algorithms include different clinical and radiologic variables; both generate low- and high-risk scores, with high-risk scores indicating a greater likelihood of suboptimal primary debulking surgery. In high-risk cases, laparoscopic evaluation of resectability was recommended, but management was based on surgeon's discretion. Of 237 patients identified, 200 had primary debulking surgery with final pathology confirming epithelial ovarian carcinoma. Of 144 patients (72%) who underwent laparotomy and primary debulking surgery, 110 (76%) were triaged directly to surgery and 34 (24%) first underwent diagnostic laparoscopy; 120 (83%) had complete gross resection, 135 (94%) had residual disease ≤1 cm, and 9 (6%) had residual disease >1 cm. Of 56 patients (28%) who underwent neoadjuvant chemotherapy, 43 (77%) first underwent diagnostic laparoscopy, and 13 (23%) were triaged directly to chemotherapy. Among all patients, 44 (22%) had high-risk scores using RS1.0 and 54 (27%) using RS2.0. RS2.0 more frequently predicted the ability to and inability to achieve complete gross resection (p > .05). RS2.0 more accurately identified high-risk disease warranting neoadjuvant chemotherapy (p = .035). Most surgeons (73%) preferred RS2.0, citing ease of use and faster calculation time. RS2.0 demonstrated favorable predictive accuracy for complete gross resection and was preferred among surgeons. The favorable complete gross resection rate (83%) highlights the value of individualized preoperative triage for primary debulking surgery versus neoadjuvant chemotherapy.