Standardizing eligibility and patient selection for Pressurized Intraperitoneal Aerosol Chemotherapy: A Delphi consensus statement.

INTRODUCTION: Pressurized Intraperitoneal Aerosol Chemotherapy (PIPAC) is a procedure for minimally invasive drug administration in patients with peritoneal metastasis. Previous studies have emphasized the importance of uniformity in treatment protocols and standardization of this practice. This study aimed to reach a consensus on eligibility, patient selection, and choice of chemotherapy for PIPAC. METHODS: A three-round modified Delphi study was conducted. A steering group formulated a list of baseline statements, addressing the objectives. The steering group consisted of seven expert surgical and medical oncologists. Available evidence and published key opinions were critically reviewed. An international expert panel scored those statements on a 4-point Likert scale. The statements were submitted electronically and anonymously. Consensus was reached if the agreement rate was ≥75%. A minimum Cronbach's alpha of >0.8 was set. RESULTS: Forty-five (45/58; 77.6%) experts participated and completed all rounds. Experts were digestive surgeons (n = 28), surgical oncologists (n = 7), gynecologists (n = 5), medical oncologists (n = 4), and one clinical researcher. Their assessment of 81 preliminary statements in the first round resulted in 41 consolidated statements. In round two, consensus was reached on 40 statements (40/41; 97.6%) with a consensus of ≥80% for each individual statement. In the third round, 40 statements were unanimously approved as definitive. The choice of first- and second-line chemotherapy remained controversial and could not reach consensus. CONCLUSIONS: This International Delphi study provides practical guidance on eligibility and patient selection for PIPAC. Ongoing trial data and long-term results that could contribute to the further standardization of PIPAC are eagerly awaited.

Anatomical knowledge enhancement through echocardiography and videos, with a spotlight on cognitive load, self-efficacy, and motivation.

In recent years, there has been a growing recognition of the importance of integrating ultrasound into undergraduate medical curricula. However, empirical evidence is lacking as to its effect on anatomy learning and related student cognition. Therefore, the present study compared the impact of echocardiography-based instruction with narrated videos on students' understanding of anatomical relationships, as well as the interaction with students' autonomous motivation, self-efficacy beliefs, mental load, and attitudes. Second-year medical students were given the opportunity to enroll in a supplementary booster course about cardiac anatomy. On the base of a randomized controlled trial with a cross-over design, we studied the effect of taking this course on spatial anatomical knowledge. After completing a pre-test (T0), students were allocated randomly to either the echocardiography-based teaching condition (cohort A) or the narrated anatomy video condition (cohort B). Next, participants were crossed over to the alternative intervention. Immediately after each phase in the intervention, students were asked to rate their mental load. Additionally, a spatial anatomical knowledge test, an autonomous motivation scale, and a self-efficacy scale were administered before (T0) and after the first intervention (T1) and at the end of the study (T2). Finally, each student completed a perception-based survey. The study design allowed a comparative evaluation of both interventions at T1, while the cross-over design facilitated the assessment of the most optimal sequencing in the interventions at T2. A total of 206 students participated (cohort A: n = 99, cohort B: n = 107). At T1, no significant differences in the knowledge test and the autonomous motivation scale were observed between cohorts A and B. However, cohort A showed higher self-efficacy beliefs compared to cohort B (p = 0.043). Moreover, cohort A reported higher levels of perceived mental load (p < 0.001). At T2, the results showed that neither sequence of interventions resulted in significant differences in anatomy scores, autonomous motivation, or self-efficacy. However, a significant difference in mental load was found again, with students in cohort B reporting a higher level of mental load (p < 0.001). Finally, based on the perception-based survey, students reported favorably on the echocardiography experience. In conclusion, the hands-on echocardiography sessions were highly appreciated by the medical students. After participating in the ultrasound sessions, they reported higher levels of self-efficacy beliefs compared to the video-based condition. However, despite embodied cognition principles, students in the echocardiography condition did not outperform students in the narrated anatomy video condition. The reported levels of mental load in the ultrasound condition could explain these findings.

Global surgery education in Belgium: Student's knowledge, attitudes and exposure.

PURPOSE: Understanding how medical students perceive global surgery will be essential in strengthening the global surgery workforce by 2030. This study investigated the knowledge, attitudes and exposure of Belgian medical students towards global surgery and identified avenues for medical institutions to include meaningful educational opportunities. METHODS: An online survey was distributed to first to final year medical students across Belgian universities using social media. Data were collected on demographics, exposure, knowledge and attitudes towards global surgery. Odds ratios with 95% confidence intervals were calculated. RESULTS: A total of 304 medical students participated from four Belgian universities. A minority reported having exposure to global surgery (24.7%), and most wanted more exposure (75.3%). Almost all respondents agreed (94.4%) that it is a relevant topic for medical students, and most agreed (71%) more compulsory education on the topic is needed. Only 13 to 44% of students could correctly answer questions testing global surgery knowledge. Personal/family responsibilities were the most important barrier to pursuing global surgery careers. CONCLUSIONS: Global surgery knowledge and exposure is limited among Belgian medical students despite interest in the field. These results advocate for the inclusion of decolonised global surgery education alongside equitable international clinical internships in medical education worldwide.

Assessing Chest Tube Insertion Skills Using a Porcine Rib Model-A Validity Study.

INTRODUCTION: Assessments require sufficient validity evidence before their use. The Assessment for Competence in Chest Tube Insertion (ACTION) tool evaluates proficiency in chest tube insertion (CTI), combining a rating scale and an error checklist. The aim of this study was to collect validity evidence for the ACTION tool on a porcine rib model according to the Messick framework. METHODS: A rib model, consisting of a porcine hemithorax that was placed in a wooden frame, was used as simulator. Participants were recruited from the departments of surgery, pulmonology, and emergency medicine. After familiarization with the rib model and the equipment, standardized instructions and clinical context were provided. They performed 2 CTIs while being scored with the ACTION tool. All performances were assessed live by 1 rater and by 3 blinded raters using video recordings. Generalizability-analysis was performed and mean scores and errors of both groups on the first performance were compared. A pass/fail score was established using the contrasting groups' method. RESULTS: Nine novice and 8 experienced participants completed the study. Generalizability coefficients where high for the rating scale (0.92) and the error checklist (0.87). In the first CTI, novices scored lower than the experienced group (38.1/68 vs. 47.1/68, P = 0.042), but no difference was observed on the error checklist. A pass/fail score of 44/68 was established. CONCLUSION: A solid validity argument for the ACTION tool's rating scale on a porcine rib model is presented, allowing formative and summative assessment of procedural skills during training before patient contact.

Descriptive review of current practices and prognostic factors in patients with ovarian cancer treated by pressurized intraperitoneal aerosol chemotherapy (PIPAC): a multicentric, retrospective, cohort of 234 patients.

Introduction: Ovarian cancer (OC) is the primary cause of mortality in women diagnosed with gynecological cancer. Our study assessed pressurized intraperitoneal aerosol chemotherapy (PIPAC) as treatment for peritoneal surface metastases (PSM) from recurrent or progressive OC and conducted survival analyses to identify prognostic factors. Material and methods: This retrospective cohort study, conducted across 18 international centers, analyzed the clinical practices of patients receiving palliative treatment for PSM from OC who underwent PIPAC. All patients were initially treated appropriately outside any clinical trial setting. Feasibility, safety, and morbidity were evaluated along with objective endpoints of oncological response. Multivariate analysis identified prognostic factors for OS and PFS. Results: From 2015-2020, 234 consecutive patients were studied, from which 192 patients were included and stratified by platinum sensitivity for analysis. Patients with early recurrence, within one postoperative month, were excluded. Baseline characteristics were similar between the groups regarding platinum sensitivity (platinum sensitive (PS) and resistant (PR)), but chemotherapy frequency differed, as did PCI before PIPAC. Median PCI decreased in both groups after three cycles of PIPAC (PS 16 vs. 12, p < 0.001; PR 24 vs. 20, p = 0.009). Overall morbidity was 22%, with few severe complications (4-8%) or mortality (0-3%). Higher pathological response and longer OS (22 vs. 11m, p = 0.012) and PFS (12 vs. 7m, p = 0.033) were observed in the PS group. Multivariate analysis (OS/PFS) identified ascites (HR 4.02, p < 0.001/5.22, p < 0.001), positive cytology at first PIPAC (HR 3.91, p = 0.002/1.96, p = 0.035), and ≥ 3 PIPACs (HR 0.30, p = 0.002/0.48, p = 0.017) as independent prognostic factors of overall survival/progression-free survival. Conclusions: With low morbidity and mortality rates, PIPAC is a safe option for palliative treatment of advanced ovarian cancer. Promising results were observed after 3 PIPAC, which did improve the peritoneal burden. However, further research is needed to evaluate the potential role of PIPAC as an independent prognostic factor.

Ultrasound versus videos: A comparative study on the effectiveness of musculoskeletal anatomy education and student cognition.

Ultrasound imaging is a dynamic imaging technique that uses high-frequency sound waves to capture live images of the structures beneath the skin. In addition to its growing use in diagnosis and interventions, ultrasound imaging has the potential to reinforce concepts in the undergraduate medical curriculum. However, research assessing the impact of ultrasound on anatomy learning and student cognition is scarce. The purpose of this study was to compare the impact of ultrasound-based instruction versus narrated videos on students' understanding of anatomical relationships, as well as the role of intrinsic motivation, self-efficacy beliefs, and students' attitudes in this process. A booster course on anterior leg and wrist anatomy was offered to second-year medical students. A randomized controlled trial with a cross-over design allocated students to either an ultrasound-based teaching condition (cohort A) or a narrated anatomy video condition (cohort B). Next, participants were crossed to the alternative intervention. At the start of the study (T0), baseline anatomy knowledge, intrinsic motivation, self-efficacy beliefs, and spatial ability were measured. After the first intervention (T1) and at the end of the study (T2), both cohorts were administered an anatomy test, an intrinsic motivation scale, and a self-efficacy scale. In addition, each student was asked to fill out a perception survey after the ultrasound intervention. Finally, building on the cross-over design, the most optimal sequence of interventions was examined. A total of 181 students participated (cohort A: n = 82, cohort B: n = 99). Both cohorts performed comparably on the baseline anatomy knowledge test, spatial ability test, intrinsic motivation, and self-efficacy scale. At T1, cohort B outperformed cohort A on the anatomy test (p = 0.019), although only a small effect size could be detected (Cohen's d = 0.34). Intrinsic motivation and self-efficacy of both cohorts were similar at T1. At T2, the anatomy test, intrinsic motivation, and self-efficacy scale did not reflect an effect after studying either sequence of the interventions. Students reported favorably about the ultrasound experience, but also mentioned a steep learning curve. Medical students found the hands-on ultrasound sessions to be valuable, increasing their interest in musculoskeletal anatomy and ultrasound imaging. However, the addition of ultrasound did not result in superior spatial anatomy understanding compared to watching anatomy videos. In addition, ultrasound teaching did not have a major effect on student cognition. Ultrasound-based teaching of musculoskeletal anatomy is regarded as difficult to learn, and therefore it is hypothesized that too high levels of cognitive load might explain the presented results.

High-grade endometrial stromal sarcoma-like' sarcoma in male: Does it exist? A case report and review of the literature.

We report an exceptional case of an undifferentiated round and spindle cell sarcoma, occurring in the periprostatic region of a 54-year-old male, with a 'high-grade endometrial stromal sarcoma-like' (HG-ESS) morphology and harboring a ZC3H7B::BCOR gene fusion identified by RNA-based next-generation sequencing. In this report, we describe the striking overlap of morphologic, immunohistochemical and molecular features of this current case and previously reported similar cases with ZC3H7B::BCOR fusion-positive HG-ESS, and discuss the differential diagnosis and possible pathogenesis of this unusual entity.

From bones to bytes: Do manipulable 3D models have added value in osteology education compared to static images?

BACKGROUND: Over the past few years, anatomy education has been revolutionized through digital media, resulting in innovative computer-based 3D models to supplement or even replace traditional learning materials. However, the added value of these models in terms of learning performance remains unclear. Multiple mechanisms may contribute to the inconclusive findings. This study focusses on the impact of active manipulation on learning performance and the influence that posttest design features may have on the outcome measurement. METHODS: Participants were randomly assigned to one of two research conditions: studying on the base of a computer-based manipulable pelvic bone model versus online static images of the same model. Pretests focused on students' baseline anatomy knowledge and spatial ability. Three knowledge posttests were administered: a test based on a physical pelvic bone model, and two computer-based tests based on static images and a manipulable model. Mental effort was measured with the Paas mental effort rating scale. RESULTS: In the static images-based posttest, significantly higher knowledge scores were attained by participants studying in the static images research condition (p = 0.043). No other significant knowledge-related differences could be observed. In the manipulable model-based posttest, spatial ability rather than the research condition seemed to have an influential role on the outcome scores (r = 0.18, p = 0.049). Mental effort scores reflected no difference between both research conditions. CONCLUSION: The research results are counter-intuitive, especially because no significant differences were found in the physical model-based posttest in students who studied with the manipulable model. Explaining the results builds on differences in anatomical models requiring less or more active manipulation to process spatial information. The pelvic bone manipulable model, and by extension osteology models, might be insufficiently complex to provide added value compared with static images. Moreover, the posttest modality should be chosen with care since spatial ability rather than anatomy knowledge may be measured.

Assessment of Treatment Response after Pressurized Intra-Peritoneal Aerosol Chemotherapy (PIPAC) for Appendiceal Peritoneal Metastases.

Background The aim of this study was to analyse survival and surrogates for oncological response after PIPAC for appendiceal tumours. Methods This retrospective cohort study included consecutive patients with appendiceal peritoneal metastases (PM) treated in experienced PIPAC centers. Primary outcome measure was overall survival (OS) from the date of diagnosis of PM and from the start of PIPAC. Predefined secondary outcome included radiological response (RECIST criteria), repeat laparoscopy and peritoneal cancer index (PCI), histological response assessed by the Peritoneal regression grading system (PRGS) and clinical response. Results Final analysis included 77 consecutive patients (208 PIPAC procedures) from 15 centres. Median OS was 30 months (23.00-46.00) from time of diagnosis and 19 months (13.00-28.00) from start of PIPAC. 35/77 patients (45%) had ≥3 procedures (pp: per protocol). Objective response at PIPAC3 was as follows: RECIST: complete response 4 (11.4%), 11 (31.4%) partial/stable; mean PRGS at PIPAC3: 1.8 ± 0.9. Median PCI: 21 (IQR 18-27) vs. 22 (IQR 17-28) at baseline (p = 0.59); 21 (60%) and 18 (51%) patients were symptomatic at baseline and PIPAC3, respectively (p = 0.873). Median OS in the pp cohort was 22.00 months (19.00-NA) from 1st PIPAC. Conclusion Patients with PM of appendiceal origin had objective treatment response after PIPAC and encouraging survival curves call for further prospective evaluation.

Structured Online Modules and Near-Peer Teaching in Neuroanatomy Stimulate Active Learning and Can Have Beneficial Effects on Medical Students' Scores.

Introduction: As a solution to a decrease in curriculum time and the continuous growth of student-staff ratio, the Ghent University uses near-peer teaching (NPT) in neuroanatomy practical sessions. To improve learning outcomes, students involved in NPT created an online module. This study evaluated the added value of the online module and investigated tutees' learning experience with NPT. Materials and Methods: A cross-sectional study was conducted on second-year medical students who followed a model trajectory. Their completion rate of the online module and results of pre- and posttests on the practical session content, the spotter test, and the theoretical exam were evaluated. Additionally, all second-year medical students were invited to complete a questionnaire on NPT and practical experience. Results: A total of 253 second year students were included. Their completion rates of the online module were moderately correlated with the spotter exam results (r = 0.37, p < 0.001). Students who completed all pretests (96.44%) scored significantly better on the spotter exam (p < 0.001). Learners who completed all posttests (50.99%) scored significantly better on the spotter test (p < 0.001). Spotter tests and theoretical exam results were moderately correlated (r = 0.50, p < 0.001). Three-quarters of 352 second year students completed the questionnaire and fully agreed on all statements that assessed NPT and the practical sessions. Conclusion: An online neuroanatomy learning module stimulates active learning and can be helpful to improve students' spotter test and neuroanatomy exam scores. NPT is a valuable teaching resource and is generally well perceived in delivering high-quality education.

Effectiveness of an immersive virtual reality environment on curricular training for complex cognitive skills in liver surgery: a multicentric crossover randomized trial.

BACKGROUND: Virtual reality (VR) is increasingly used in surgical education, but evidence of its benefits in complex cognitive training compared to conventional 3-dimensional (3D) visualization methods is lacking. The objective of this study is to assess the impact of 3D liver models rendered visible by VR or desktop interfaces (DIs) on residents' performance in clinical decision-making. METHOD: From September 2020 to April 2021, a single-blinded, crossover randomized educational intervention trial was conducted at two university hospitals in Belgium and Italy. A proficiency-based stepwise curriculum for preoperative liver surgery planning was developed for general surgery residents. After completing the training, residents were randomized in one of two assessment sequences to evaluate ten real clinical scenarios. RESULTS: Among the 50 participants, 46 (23 juniors/23 seniors) completed the training and were randomized. Forty residents (86.96%) achieved proficiency in decision-making. The accuracy of virtual surgical planning using VR was higher than that using DI in both groups A (8.43 ± 1.03 vs 6.86 ± 1.79, p < 0.001) and B (8.08 ± 0.9 vs 6.52 ± 1.37, p < 0.001). CONCLUSION: Proficiency-based curricular training for liver surgery planning successfully resulted in the acquisition of complex cognitive skills. VR was superior to DI visualization of 3D models in decision-making. GOV ID: NCT04959630.

Assessing competence in Chest Tube Insertion with the ACTION-tool: A Delphi study.

INTRO: Chest Tube Insertion (CTI) should be trained in simulated settings prior to patient contact. Feedback and certification is based on valid assessments, especially in simulation-based training. This study aimed to develop a novel assessment tool for CTI and to ensure content validity based on expert opinion collected through a structured Delphi study. METHODS: A diverse European expert panel was invited to participate. In round 1, the experts provided at least five procedural steps and three errors involved in CTI. Round 2 evaluated the level of agreement with the inclusion of each item in the assessment tool on a five-point Likert scale. In round 3, experts rated their agreement on inclusion of the procedural step with its descriptive anchors. Consensus was reached when ≥80% of participants agreed on an item's inclusion. RESULTS: Thirty-six of 105 (34%) invited surgeons (26/75, 35%), pulmonologists (8/23, 35%) and emergency physicians (2/7, 29%) participated. The overall response rate was 81% (29/36): 100% (36/36) in round 1, 83% (30/36) in round 2, and 97% (29/30) in round 3. Round 1 resulted in 23 steps and 44 errors after condensation and removal of duplicates. In round 2 consensus was achieved for 15 steps (65%) and 14 errors (32%). Nineteen steps were adapted into a rating scale with descriptive anchors and a list of 16 errors was presented to the panel. In round 3, experts reached consensus on the inclusion of 17 procedural steps (89%) with descriptive anchors and on all 16 errors. CONCLUSION: A multidisciplinary expert panel achieved consensus in the development of the ACTION (Assessment of Competence in Chest Tube Insertion) tool. This procedure-specific rating scale of 17 steps, supplemented with a checklist of 16 errors, requires further research to collect validity evidence.

Phase I study of intraperitoneal aerosolized nanoparticle albumin based paclitaxel (NAB-PTX) for unresectable peritoneal metastases.

BACKGROUND: Pressurized intraperitoneal aerosolized chemotherapy (PIPAC) is a novel method to treat patients with peritoneal metastases (PM). We aimed to study the tolerability, safety, pharmacokinetics, and tumour response of nanoparticle albumin bound paclitaxel (NAB-PTX) during PIPAC in a Phase I study. METHODS: Eligible patients with biopsy-proven PM from ovarian, breast, gastric, hepatobiliary, or pancreatic origin underwent three PIPAC treatments using NAB-PTX with a four-week interval. The dose of NAB-PTX was escalated from 35 to 140 mg/m2 using a Bayesian design to estimate the maximum tolerated dose (MTD). FINDINGS: Twenty-three patients were included; thirteen (65%) patients combined PIPAC therapy with continued systemic chemotherapy. The most frequent toxicities were liver toxicity and anaemia. Treatment resulted in seven (35%) responders, six (30%) non-responders and seven (35%) patients with stable PM. Systemic absorption of NAB-PTX was slow, with median peak plasma concentrations reached after 3 to 4 h. Median NAB-PTX tumour tissue concentrations suggested accumulation: 14.6 ng/mg, 19.2 ng/mg and 40.8 ng/mg after the first, second and third PIPAC procedure respectively. EORTC QoL and VAS scores remained stable. Overall survival after one year was 57%. INTERPRETATION: PIPAC with NAB-PTX results in a favourable PK profile and promising anticancer activity in patients with unresectable PM. The MTD and recommended Phase II clinical trial dose are 140 mg/m2. In patients with impaired hepatobiliary function, a dose of 112.5 mg/m2 is recommended. FUNDING: Kom op tegen Kanker (Flemish League against Cancer).

A clinically annotated post-mortem approach to study multi-organ somatic mutational clonality in normal tissues.

Recent research on normal human tissues identified omnipresent clones of cells, driven by somatic mutations known to be responsible for carcinogenesis (e.g., in TP53 or NOTCH1). These new insights are fundamentally changing current tumor evolution models, with broad oncological implications. Most studies are based on surgical remnant tissues, which are not available for many organs and rarely in a pan-organ setting (multiple organs from the same individual). Here, we describe an approach based on clinically annotated post-mortem tissues, derived from whole-body donors that are routinely used for educational purposes at human anatomy units. We validated this post-mortem approach using UV-exposed and unexposed epidermal skin tissues and confirm the presence of positively selected NOTCH1/2-, TP53- and FAT1-driven clones. No selection signals were detected in a set of immune genes or housekeeping genes. Additionally, we provide the first evidence for smoking-induced clonal changes in oral epithelia, likely underlying the origin of head and neck carcinogenesis. In conclusion, the whole-body donor-based approach provides a nearly unlimited healthy tissue resource to study mutational clonality and gain fundamental mutagenic insights in the presumed earliest stages of tumor evolution.

Feasibility and safety of PIPAC combined with additional surgical procedures: PLUS study.

BACKGROUND: PIPAC (Pressurized IntraPeritoneal Aerosol Chemotherapy) is a minimally invasive approach relying on physical principles for improving intraperitoneal drug delivery, including optimizing the homogeneity of drug distribution through an aerosol. Feasibility and safety of the new approach are now consolidated and data on its effectiveness are continuously increasing. Although any surgical procedure associated with PIPAC had always been discouraged due to the high risk of complications, surgical practice is constantly changing: with growing expertise, more and more surgical teams associate PIPAC with surgery. METHODS: PLUS study is part of the retrospective international cohort studies including 10 centers around the world (India, Italy, France, Germany, Belgium, Russia, Saudi Arabia, Switzerland) and 96 cases of combined approaches evaluated through a propensity score analysis. RESULTS: the procedures most frequently associated with PIPAC were not only adhesiolysis, omentectomy, adnexectomy, umbilical/inguinal hernia repairs, but also more demanding procedures such as intestinal resections, gastrectomy, splenectomy, bowel repair/stoma creation. Although the evidence is currently limited, PLUS study demonstrated that PIPAC associated with additional surgical procedures is linked to an increase of surgical time (p < 0.001), length of stay (p < 0.001) and medical complication rate (p < 0.001); the most frequently reported medical complications were mild or moderate in severity, such as abdominal pain, nausea, ileus and hyperthermia. No difference in terms of surgical complications was registered; neither reoperation or postoperative deaths were reported. CONCLUSIONS: these results suggest that PIPAC can be safely combined in expert centers with additional surgeries. Widespread change of practice should be discouraged before the results of ongoing prospective studies are available.

Digital body preservation: Technique and applications.

High-fidelity anatomical models can be produced with three-dimensional (3D) scanning techniques and as such be digitally preserved, archived, and subsequently rendered through various media. Here, a novel methodology-digital body preservation-is presented for combining and matching scan geometry with radiographic imaging. The technique encompasses joining layers of 3D surface scans in an anatomical correct spatial relationship. To do so, a computed tomography (CT) volume is used as template to join and merge different surface scan geometries by means of nonrigid registration into a single environment. In addition, the use and applicability of the generated 3D models in digital learning modalities is presented. Finally, as computational expense is usually the main bottleneck in extended 3D applications, the influence of mesh simplification in combination with texture mapping on the quality of 3D models was investigated. The physical fidelity of the simplified meshes was evaluated in relation to their resolution and with respect to key anatomical features. Large- and medium-scale features were well preserved despite extensive 3D mesh simplification. Subtle fine-scale features, particular in curved areas demonstrated the major limitation to extensive mesh size reduction. Depending on the local topography, workable mesh sizes ranging from 10% to 3% of the original size could be obtained, making them usable in various learning applications and environments.

Optimization of intraperitoneal aerosolized drug delivery using computational fluid dynamics (CFD) modeling.

Intraperitoneal (IP) aerosolized anticancer drug delivery was recently introduced in the treatment of patients with peritoneal metastases. However, little is known on the effect of treatment parameters on the spatial distribution of the aerosol droplets in the peritoneal cavity. Here, computational fluid dynamics (CFD) modeling was used in conjunction with experimental validation in order to investigate the effect of droplet size, liquid flow rate and viscosity, and the addition of an electrostatic field on the homogeneity of IP aerosol. We found that spatial distribution is optimal with small droplet sizes (1-5 µm). Using the current clinically used technology (droplet size of 30 µm), the optimal spatial distribution of aerosol is obtained with a liquid flow rate of 0.6 mL s-1. Compared to saline, nebulization of higher viscosity liquids results in less homogeneous aerosol distribution. The addition of electrostatic precipitation significantly improves homogeneity of aerosol distribution, but no further improvement is obtained with voltages higher than 6.5 kV. The results of the current study will allow to choose treatment parameters and settings in order to optimize spatial distribution of IP aerosolized drug, with a potential to enhance its anticancer effect.

Treatment Response After Pressurized IntraPeritoneal Aerosol Chemotherapy (PIPAC) for Peritoneal Metastases of Colorectal Originf.

The objective of this study is to analyze oncological outcomes of patients with peritoneal metastases (PM) of colorectal origin treated with Pressurized IntraPeritoneal Aerosol Chemotherapy (PIPAC). Background: PIPAC has been demonstrated to be a feasible and safe novel treatment for patients with PM of various origins. Only small series reports on survival after PIPAC by disease entity. Methods: International retrospective cohort study of consecutive patients with PM of colorectal origin. Outcome measures were overall survival (OS), radiological response according to Response Evaluation Criteria in Solid Tumors (RECIST), histological response (peritoneal regression grading score [PRGS]: complete response: 1-4: no response), change of peritoneal cancer index (PCI), and symptom control. Results: Seventeen eligible centers compiled 256 non-selected patients (mean age 61 [50.6-69.2], 43% female) and 606 procedures. Sixty-three percent were treated after 2 lines of chemotherapy, median PCI at PIPAC1 was 18 (interquartile range [IQR] = 10-27). Median OS was 19.00 months (IQR = 12.9-29.8) from diagnosis and 9.4 months (IQR = 4.5-16.8) from PIPAC1. One hundred and four of 256 patients (40.6%) had ≥3 procedures (per protocol [pp]) with the following outcomes at PIPAC3: RECIST: 59.3% partial response/stable, 40.7% progression; mean PRGS: 2.1 ± 0.9. Median PCI was 21 (IQR = 15-29) at baseline and 20 (IQR = 12-27) at PIPAC3 (P = 0.02). Fifty-six (54%) and 48 (46%) patients were symptomatic at baseline and PIPAC3, respectively (P = 0.267). Median OS for the pp cohort was 11.9 months (IQR = 10.7-15.0) from PIPAC1. Independent predictors for survival were radiological response (HR = 3.0; 95% CI = 1.6-5.7) and no symptoms (HR = 4.5, 95% CI = 2.2-9.1) at PIPAC3. Conclusions: Objective treatment response and encouraging survival were demonstrated after PIPAC for colorectal PM. Prospective registry data and comparative studies are now needed in to confirm these data.