Morbidity after secondary cytoreductive surgery with or without hyperthermic intraperitoneal chemotherapy for ovarian cancer: An analysis of a randomized phase II trial.

OBJECTIVE: To assess postoperative complications after secondary cytoreductive surgery (SCS) with or without hyperthermic intraperitoneal chemotherapy (HIPEC), we conducted an exploratory analysis of patients with platinum-sensitive recurrent ovarian cancer enrolled in a randomized phase II trial. METHODS: Complications occurring within 30 days of surgery were graded using Common Terminology Criteria for Adverse Events (CTCAE) version 5.0; only hemoglobin and platelet levels were assessed. Patients were grouped by CTCAE grade ≥ 3 and < 3 complications. RESULTS: Among 83 eligible patients, 33 (40%) had grade ≥ 3 complications and 50 (60%) had grade < 3 complications; anemia and abdominal infections were the most common. There were no perioperative mortalities. Time to initiation of postoperative chemotherapy for patients with grade ≥ 3 and grade < 3 events was 34 days (range, 18-60) and 31 days (range, 21-43), respectively (P = .017). Median progression-free survival (PFS) did not significantly differ between patients with grade ≥ 3 and grade < 3 complications (11.2 months [95% CI: 9.3-14.4] vs 14.9 months [95% CI: 11.3-16.5], respectively; P = .186), nor did median overall survival (OS) (46.9 months [95% CI: 34-NE] vs 68.2 months [95% CI: 52.1-NE], respectively; P = .053). CONCLUSION: Postoperative complications following SCS with or without HIPEC were associated with slight delays in chemotherapy initiation but did not significantly impact oncologic outcomes.

Secondary Cytoreduction and Carboplatin Hyperthermic Intraperitoneal Chemotherapy for Platinum-Sensitive Recurrent Ovarian Cancer: An MSK Team Ovary Phase II Study.

PURPOSE: The purpose of this phase II study was to evaluate hyperthermic intraperitoneal chemotherapy (HIPEC) with carboplatin for recurrent ovarian cancer during secondary cytoreductive surgery. MATERIALS AND METHODS: Patients were intraoperatively randomly assigned to carboplatin HIPEC (800 mg/m2 for 90 minutes) or no HIPEC, followed by five or six cycles of postoperative IV carboplatin-based chemotherapy, respectively. Based on a binomial single-stage pick-the-winner design, an arm was considered winner if ≥ 17 of 49 patients were without disease progression at 24 months post-surgery. Secondary objectives included postoperative toxicity and HIPEC pharmacokinetics. RESULTS: Of 98 patients, 49 (50%) received HIPEC. Complete gross resection was achieved in 82% of the HIPEC patients and 94% of the standard-arm patients. Bowel resection was performed in 37% of patients in the HIPEC arm compared with 65% in the standard (P = .008). There was no perioperative mortality and no difference in use of ostomies, length of stay, or postoperative toxicity. At 24 months, eight patients (16.3%; 1-sided 90% CI, 9.7 to 100) were without progression or death in the HIPEC arm and 12 (24.5%; 1-sided 90% CI, 16.5 to 100) in the standard arm. With a medium follow-up of 39.5 months, 82 patients progressed and 37 died. The median progression-free survival in the HIPEC and standard arms were 12.3 and 15.7 months, respectively (hazard ratio, 1.54; 95% CI, 1 to 2.37; P = .05). There was no significant difference in median overall survival (52.5 v 59.7 months, respectively; hazard ratio, 1.39; 95% CI, 0.73 to 2.67; P = .31). These analyses were exploratory. CONCLUSION: HIPEC with carboplatin was well tolerated but did not result in superior clinical outcomes. This study does not support the use of HIPEC with carboplatin during secondary cytoreductive surgery for platinum-sensitive recurrent ovarian cancer.

Reducing sugar and aroma in a confectionery gel without compromising flavour through addition of air inclusions.

Sugar plays an important role in both the flavour and structure of confectionery. Targets have been set to reduce sugar; however, common strategies often result in changes in flavour and consumer rejection. In this study, an approach was developed to reduce sugar in confectionery gels by aeration, without significantly affecting perceived chewiness. Gelatine based gels with a 23% and 38% reduction in density were formulated using aeration. Mean bubble size was consistent across all gels (0.05-0.06 mm). Time-intensity sensory evaluation was carried out by a trained sensory panel (n = 10). With aeration, no significant difference in overall flavour perception was observed in the 23% and 38% reduced sugar and aroma gels. Air inclusions create a greater surface area, therefore accelerating mass transfer of volatiles and release of sucrose at the food-saliva interface. Consequently, we propose that less calorie dense products can be produced without compromising flavour by using gel aeration technologies.

Flavour distribution and release from gelatine-starch matrices.

Microstructure design of protein-polysaccharide phase separated gels has been suggested as a strategy to nutritionally improve food products. Varying the phase volumes of a phase separated matrix may affect texture and overall flavour balance of the final product, which are both important for consumer acceptance. The aims of this study were to investigate how modifying the phase volumes of a gelatine-starch biphasic mixture affected aroma release, and how addition of sucrose affects phase separation, flavour distribution and aroma release. Biphasic gels of different microstructures with the same effective concentration of gelatine and starch in each phase were developed. Microstructure significantly affected aroma release in vitro but not in vivo when panellists (n = 5) chewed and swallowed the sample. Addition of sucrose (0-60%) to the biphasic mixture significantly reduced water activity, affected the microstructure and affected aroma distribution in each phase and subsequent release rates depending on the physicochemical properties of the aroma volatile. In general, affinity for the gelatine phase for the less hydrophobic, more volatile compounds was not significantly affected by sucrose concentration. Whereas an increased affinity for the starch phase for the more hydrophobic, less volatile compounds was observed with increased sucrose as the starch phase becomes more dispersed at sucrose concentrations between 40 and 60%. The results of this study may be of interest to researchers and industry to enable prediction of how reformulation, such as reduction of sucrose, to meet nutritional guidelines may affect the overall aroma balance of a phase separated food matrix.

Anxiety Cells in a Hippocampal-Hypothalamic Circuit.

The hippocampus is traditionally thought to transmit contextual information to limbic structures where it acquires valence. Using freely moving calcium imaging and optogenetics, we show that while the dorsal CA1 subregion of the hippocampus is enriched in place cells, ventral CA1 (vCA1) is enriched in anxiety cells that are activated by anxiogenic environments and required for avoidance behavior. Imaging cells defined by their projection target revealed that anxiety cells were enriched in the vCA1 population projecting to the lateral hypothalamic area (LHA) but not to the basal amygdala (BA). Consistent with this selectivity, optogenetic activation of vCA1 terminals in LHA but not BA increased anxiety and avoidance, while activation of terminals in BA but not LHA impaired contextual fear memory. Thus, the hippocampus encodes not only neutral but also valence-related contextual information, and the vCA1-LHA pathway is a direct route by which the hippocampus can rapidly influence innate anxiety behavior.