Assessment of Intraoperative Scoring Systems for Predicting Cytoreduction Outcome in Peritoneal Metastatic Disease: A Systematic Review and Meta-analysis.

BACKGROUND: Cytoreductive surgery (CRS) is a widely acknowledged treatment approach for peritoneal metastasis, showing favorable prognosis and long-term survival. Intraoperative scoring systems quantify tumoral burden before CRS and may predict complete cytoreduction (CC). This study reviews the intraoperative scoring systems for predicting CC and optimal cytoreduction (OC) and evaluates the predictive performance of the Peritoneal Cancer Index (PCI) and Predictive Index Value (PIV). METHODS: Systematic searches were conducted in Embase, MEDLINE, and Web of Science. Meta-analyses of extracted data were performed to compare the absolute predictive performances of PCI and PIV. RESULTS: Thirty-eight studies (5834 patients) focusing on gynecological (n = 34; 89.5%), gastrointestinal (n = 2; 5.3%) malignancies, and on tumors of various origins (n = 2; 5.3%) were identified. Seventy-seven models assessing the predictive performance of scoring systems (54 for CC and 23 for OC) were identified with PCI (n = 39/77) and PIV (n = 16/77) being the most common. Twenty models (26.0%) reinterpreted previous scoring systems of which ten (13%) used a modified version of PIV (reclassification). Meta-analyses of models predicting CC based on PCI (n = 21) and PIV (n = 8) provided an AUC estimate of 0.83 (95% confidence interval [CI] 0.79-0.86; Q = 119.6, p = 0.0001; I2 = 74.1%) and 0.74 (95% CI 0.68-0.81; Q = 7.2, p = 0.41; I2 = 11.0%), respectively. CONCLUSIONS: Peritoneal Cancer Index models demonstrate an excellent estimate of CC, while PIV shows an acceptable performance. There is a need for high-quality studies to address management differences, establish standardized cutoff values, and focus on non-gynecological malignancies.

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.

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.

Using an application to measure trainees' procedural knowledge before chest tube insertion.

PURPOSE OF THE STUDY: To collect validity evidence for the chest tube insertion (CTI) test mode on the medical simulation application Touch Surgery. This was done by using Messick's contemporary framework. METHODS: Novice, intermediate and experienced participants provided informed consent and demographic information. After familiarisation with the application, they completed the CTI test mode. Validity evidence was collected from four sources: content, response process, relation to other variables and consequences. A post-study questionnaire with 5-point Likert scales assessed the perceived realism, relevance and utility of the assessment. Mean scores of the three groups were compared. RESULTS: A total of 25 novices, 11 intermediates and 19 experienced participants were recruited. Content evidence was collected by an expert in CTI and was based on published literature and guidelines. All users were familiarised with the application, and received standardised instructions throughout the test. Most users rated the simulation as realistic and suitable to assess cognitive skills. Novices received significantly lower (55.9±7.5) test mode scores than intermediates (80.6±4.4) (p<0.001) and experienced participants (82.3±5.3) (p<0.001). There was no significant difference in score between intermediate and experienced participants (p=0.75). Consequences evidence was provided by establishing a pass/fail score of 71% using the contrasting groups method, which resulted in one observed false positive and no false negatives. CONCLUSION: A robust validity argument was constructed for the CTI test mode, which can be implemented in surgical curricula to assess learners' cognitive skills prior to hands-on simulation practice.

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.

Incidentally found mucinous epithelial tumors of the appendix with or without pseudomyxoma peritonei: diagnostic and therapeutic algorithms based on current evidence.

Mucinous appendiceal tumors with or without the pseudomyxoma peritonei (PMP) syndrome are rare, but often present as an incidental finding. The confusing histology and lack of large prospective trials result in a considerable diagnostic and therapeutic challenge in these patients. We propose treatment algorithms in patients with incidentally found mucinous epithelial appendiceal tumors, with or without PMP, based on the currently available evidence. The therapeutic approach should take into account the histology and grade of the primary appendix tumor, as well as those of the associated peritoneal disease.

Key components of a hepatobiliary surgery curriculum for general surgery residents: results of the FULCRUM International Delphi consensus.

BACKGROUND: In general surgery residency, hepatobiliary training varies significantly across the world. The aim of this study was to establish an international consensus among hepatobiliary surgeons on components of a hepatobiliary curriculum for general surgery residents. METHODS: A three-round modified Delphi technique was employed. Fifty-two hepatobiliary surgeons involved in general surgery training programs were invited. An initial questionnaire was developed by a group of experts in hepatobiliary and educational research after a systematic literature review. It comprised 90 statements about knowledge, technical skills, attitudes, and postoperative care. Panelists could add or alter items. The survey was delivered electronically and the panel was instructed to score the items based on 5-point Likert scale. Consensus was reached when at least 80% of panelists agreed on a statement with Cronbach's alpha value >0.8. RESULTS: Forty-one (79%) experts have participated. Sixteen panelists are based in Asia, 14 in Europe, and 11 in the Americas. Eighty percent of all proposed skills (81/101) were considered fundamental including knowledge (39/43), technical skills (16/32), attitude (15/15), and postoperative care (11/11). CONCLUSION: An international consensus was achieved on components of a hepatobiliary curriculum. Acquiring broad knowledge is fundamental during residency. Advanced liver resection techniques require specialized hepatobiliary training.

Establishment of a rat ovarian peritoneal metastasis model to study pressurized intraperitoneal aerosol chemotherapy (PIPAC).

BACKGROUND: pressurized intraperitoneal aerosol chemotherapy (PIPAC), with or without electrostatic precipitation (ePIPAC), was recently introduced in the treatment of peritoneal metastases (PM) from ovarian cancer (OC). Preliminary clinical data are promising, but several methodological issues as well the anticancer efficacy of PIPAC remain unaddressed. Here, we propose a rat ePIPAC model that allows to study these issues in a clinically relevant, reproducible, and high throughput model. METHODS: laparoscopy and PIPAC were established in healthy Wistar rats. Aerosol properties were measured using laser diffraction spectrometry based granulometric analyses. Electrostatic precipitation was accomplished using a commercially available generator (Ultravision™). A xenograft model of ovarian PM was created in athymic rats using intraperitoneal (IP) injection of SKOV-3 luciferase positive cells. Tumor growth was monitored weekly by in vivo bioluminescence imaging. RESULTS: PIPAC and electrostatic precipitation were well tolerated using a capnoperitoneum of 8 mmHg. All rats survived the (e)PIPAC procedure and no gas or aerosol leakage was observed over the entire procedure. With an injection pressure of 20 bar, granulometry showed a mean droplet diameter (D(v,0.5)) of 47 µm with a flow rate of 0.5 mL/s, and a significantly lower diameter (30 µm) when a flow rate of 0.8 mL/s was used. Experiments using IP injection of SKOV-3 luciferase positive cells showed that after IP injection of 20 × 106 cells, miliary PM was observed in all animals. PIPAC was feasible and well supported in these tumor bearing animals. CONCLUSIONS: we propose a reproducible and efficient rodent model to study PIPAC and ePIPAC in OC xenografts with widespread PM. This model allows to characterize and optimize pharmacokinetic and biophysical parameters, and to evaluate the anti-cancer efficacy of (e)PIPAC treatment.

High Pressure Nebulization (PIPAC) Versus Injection for the Intraperitoneal Administration of mRNA Complexes.

PURPOSE: Pressurized intraperitoneal aerosol chemotherapy (PIPAC) is a novel technique delivering drugs into the abdominal cavity as an aerosol under high pressure. It is hypothesized to have advantages such as enhancing tissue uptake, distributing drugs homogeneously within the closed and expanded abdominal cavity and higher local concentration of drugs in the peritoneal cavity. However, the clinical trials of PIPAC so far are limited to liquid chemotherapeutic solution, and the applicability of biomolecules (such as mRNA, siRNA and oligonucleotide) is not known. We aimed to investigate the feasibility of administrating mRNA lipoplexes to the peritoneal cavity via high pressure nebulization. METHODS: We firstly investigated the influences of nebulization on physicochemical properties and in vitro transfection efficiency of mRNA lipoplexes. Then, mRNA lipoplexes were delivered to healthy rats through intravenous injection, intraperitoneal injection and PIPAC, respectively. RESULTS: mRNA lipoplexes can withstand the high pressure applied during the PIPAC procedure in vitro. Bioluminescence localized to the peritoneal cavity of rats after administration by IP injection and nebulization, while intravenous injection mainly induced protein expression in the spleen. CONCLUSION: This study demonstrated that local nebulization is feasible to apply mRNA complexes in the peritoneal cavity during a PIPAC procedure.

Laparoscopic Liver Surgery Training Course on Thiel-Embalmed Human Cadavers: Program Evaluation, Trainer's Long-Term Feedback and Steps Forward.

OBJECTIVES: The purpose of this study was to evaluate the feedback of participants upon laparoscopic liver surgery (LLS) course on Thiel-embalmed human bodies. METHODS: From 2010 to 2017, ten LLS masterclasses have been organized by the Department of Hepatobiliary Surgery at Ghent University Hospital. A 23-question anonymous survey was electronically sent to 119 participants between November 2017 and January 2018, exploring their characteristics and asking for evaluation of the course. The obstacles for implementing LLS in their centers have been assessed. RESULTS: Sixty-four surgeons (53.8%) responded to the survey; 42 (65.6%) were employed at a university hospital; and 39 (60.9%) were in the first decade of their practice as a consultant surgeon. Forty-three (67.2%) surgeons reported an increased percentage of LLS cases afterward. Training on Thiel cadavers was considered superior (49.2%) to other training options including proctoring in the operating room (34.9%), virtual reality (6.3%), video training (4.8%) and practicing on pigs (4.8%). Obstacles identified contained inadequate training, patient's referral pattern, financial issues, lack of dedicated surgical team and time constrains. CONCLUSIONS: This survey revealed that a structured short-time program incorporating interactive discussion, live operations and hands-on training on human bodies under proctorship may enhance efficient training in laparoscopic liver surgery. In a step forward for upcoming courses, the importance of team building has to be addressed.

Biology-Based Surgery: The Extent of Lymphadenectomy in Cancer of the Colon.

The progression of colon cancer (CC) involves hematogenous and lymphatic spread to locoregional lymph nodes (LN), distant LN, and metastatic sites including the liver. The biological mechanisms that govern CC progression remain elusive. The Halsted model assumes an orderly, stepwise progression from the primary tumor to nearby nodes, henceforth to anatomically more distant nodes, and ultimately to distant organs. The Fisher model, on the other hand, regards the release of metastatic cells as early and essentially random events. The underlying biology has important implications for the ideal extent of surgery: when the Fisher model is correct, efforts to remove apical (central), extramesenteric, or para-aortic LN are unlikely to affect the oncological outcome. Recent data from phylogenetic studies suggest that cancer cell populations differ genetically among different LN stations and from distant metastases. Circulating tumor cells and other liquid biomarkers can be detected in the circulation of patients with early-stage disease. Local recurrence in CC is uncommon, and it is associated with a high risk of systemic progression and poor survival. Clinical studies comparing standard colectomy with extensive surgery (high ligation of the inferior mesenteric artery, complete mesocolic excision, D3 dissection, and para-aortic or extramesenteric node dissection) show that these techniques increase the LN count, while any beneficial effect on the risk of local recurrence or disease-free survival is at present uncertain due to the lack of controlled trials. Ongoing randomized trials comparing extensive vs. standard surgery for CC will generate important answers.

Systematic review of surgical training on reperfused human cadavers.

BACKGROUND: The role of reperfused human cadavers in surgical training has not been established. METHODS: Reports describing reperfused human cadaver models in terms of simulated surgeries, the use of tools to assess technical competency and skills transfer to patients, cadaver status and reperfusion techniques were included. RESULTS: Thirty-five reports were included. Most participants practised vascular (n = 27), flap (n = 6) and trauma (n = 4) procedures. Training progression was evaluated objectively in only two studies. In two publications, flap techniques were practised on cadavers and repeated successfully in patients. Eighteen studies employed whole bodies. Fresh and embalmed cadavers were both used in 17 publications. Most embalmed cadavers were formalin-fixed (n = 10), resulting in stiffness. Few trainings were offered on soft Thiel-embalmed cadavers (n = 5). Only arteries were reperfused in 20 studies, while in 13 publications, the arteries and veins were filled. Arteries and/or veins were mostly pressurized (n = 21) and arterial flow was generated in 14 studies. CONCLUSIONS: Various reperfused human cadaver models exist, enabling practise of mainly vascular procedures. Preservation method determines the level of simulation fidelity. Thorough evaluation of these models as surgical training tools and transfer effectiveness is still lacking.

Effect of abdominopelvic sepsis on cancer outcome in patients undergoing sphincter saving surgery for rectal cancer.

BACKGROUND: In rectal cancer, the significance of abdominopelvic sepsis (APS) on metastatic tumor growth remains uncertain. We aimed to analyze the effect of abdominopelvic sepsis on long-term survival in patients undergoing restorative rectal cancer surgery. METHODS: Data were used from the Belgian PROCARE rectal cancer registry. The effect of abdominopelvic infection on survival was assessed in uni- and multivariable Cox regression models. The effect of clinical and pathological covariates was controlled by propensity score-based matching of cases with controls. The effect of abdominopelvic sepsis on the rate of local and metastatic recurrence was evaluated using crosstabulation and the Pearson χ2 test. RESULTS: In univariable analysis, the presence of APS was associated with significantly worse overall survival (HR 1.3, P = 0.025). After propensity score matching including age, BMI, tumor level, pTstage, pN stage, CRM, tumor grade, number of lymph nodes, and presence of lymphovascular invasion, the association of APS with OS was no longer significant (HR 1.26, 95%CI 0.92-1.74, P = 0.15). No differences were observed in the risk of local or metastatic recurrence (3.6% vs 2.9% and 13% vs 16.5%). CONCLUSIONS: In this analysis APS after rectal cancer resection was not significantly associated with OS, metastatic, or local recurrence.

Effect of Neoadjuvant Radiation Dose and Schedule on Nodal Count and Its Prognostic Impact in Stage II-III Rectal Cancer.

BACKGROUND: It is unknown how neoadjuvant treatment schedule affects lymph node count (LNC) and lymph node ratio (LNR) and how these correlate with overall survival (OS) in rectal cancer (RC). METHODS: Data were used from the Belgian PROCARE rectal cancer registry on RC patients treated with surgery alone, short-term radiotherapy with immediate surgery (SRT), or chemoradiation with deferred surgery (CRT). The effect of neoadjuvant therapy on LNC was examined using Poisson log-linear analysis. The association of LNC and LNR with overall survival (OS) was studied using Cox proportional hazards models. RESULTS: Data from 4037 patients were available. Compared with surgery alone, LNC was reduced by 12.3 % after SRT and by 31.3 % after CRT (p < 0.001). In patients with surgery alone, the probability of finding node-positive disease increased with LNC, while after SRT and CRT no increase was noted for more than 12 and 18 examined nodes, respectively. Per node examined, we found a decrease in hazard of death of 2.7 % after surgery alone and 1.5 % after SRT, but no effect after CRT. In stage III patients, the LNR but not (y)pN stage was significantly correlated with OS regardless of neoadjuvant therapy. Specifically, a LNR > 0.4 was associated with a significantly worse outcome. CONCLUSIONS: Nodal counts are reduced in a schedule-dependent manner by neoadjuvant treatment in RC. After chemoradiation, the LNC does not confer any prognostic information. A LNR of >0.4 is associated with a significantly worse outcome in stage III disease, regardless of neoadjuvant therapy type.

Lifelike Vascular Reperfusion of a Thiel-Embalmed Pig Model and Evaluation as a Surgical Training Tool.

BACKGROUND: Vascular reperfusion of Thiel cadavers can aid surgical and anatomical instruction. This study investigated whether ideal embalming circumstances provide lifelike vascular flow, enabling surgical practice and enhancing anatomical reality. METHODS: Pressure-controlled pump-driven administration of blue embalming solution was assessed directly postmortem in a pig model (n = 4). Investigation of subsequent pump-driven vascular injection of red paraffinum perliquidum (PP) included assessment of flow parameters, intracorporeal distribution, anatomical alterations, and feasibility for surgical training. The microscopic distribution of PP was analyzed in pump-embalmed pig and gravity-embalmed human small intestines. RESULTS: Embalming lasted 50-105 min, and maximum arterial pressure was 65 mm Hg. During embalming, the following consecutive alterations were observed: arterial filling, organ coloration, venous perfusion, and further tissue coloration during the next weeks. Most organs were adequately preserved. PP generated low arterial pressures (<30 mm Hg) and drained through the venous cannula. Generally, realistic reperfusion and preservation of original anatomy were observed, but leakage in the pleural, abdominal, and retroperitoneal cavities occurred, and computed tomography showed edematous spleen and liver. Reduction of arterial flow rates after venous drainage is a prerequisite to prevent anatomical deformation, allowing simulation of various surgeries. In pump-embalmed pig small intestines, PP flowed from artery to vein through the capillaries without extravasation. In contrast, arterioles were blocked in gravity-embalmed human tissues. CONCLUSIONS: In a pig model, immediate postmortem pressure-controlled pump embalming generates ideal circumstances for (micro)vascular reperfusion with PP, permitting lifelike anatomy instruction and surgical training.

BEV-IP: Perioperative chemotherapy with bevacizumab in patients undergoing cytoreduction and intraperitoneal chemoperfusion for colorectal carcinomatosis.

BACKGROUND: Selected patients with peritoneal carcinomatosis (PC) from colorectal cancer (CRC) benefit from cytoreductive surgery (CRS) combined with intraperitoneal chemoperfusion (IPC). However, even after optimal cytoreduction, systemic and locoregional recurrence are common. Perioperative chemotherapy with bevacizumab (BEV) may improve the outcome of these patients. METHODS/DESIGN: The BEV-IP study is a phase II, single-arm, open-label study aimed at patients with colorectal or appendiceal adenocarcinoma with synchronous or metachronous PC. This study evaluates whether perioperative chemotherapy including BEV in combination with CRS and oxaliplatin-based IPC results in acceptable morbidity and mortality (primary composite endpoint). Secondary endpoints are treatment completion rate, chemotherapy-related toxicity, pathological response, progression free survival, and overall survival. DISCUSSION: The BEV-IP trial is the first prospective assessment of the safety and efficacy of perioperative chemotherapy combined with anti-angiogenic treatment in patients undergoing CRS and IPC for colorectal peritoneal metastases. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02399410 EudraCT number: 2015-001187-19 (registered March 9, 2015).

Intraperitoneal chemotherapy (IPC) for peritoneal carcinomatosis: review of animal models.

The development of suitable animal models is essential to experimental research on intraperitoneal chemotherapy (IPC). This review of the English literature (MEDLINE) presents a detailed analysis of current animal models and gives recommendations for future experimental research. Special consideration should be given to cytotoxic drug dose and concentration, tumor models, and outcome parameters.

Postmortem circulation: a new model for testing endovascular devices and training clinicians in their use.

The development of new medical devices, such as aortic valves, requires numerous preliminary studies on animals and training of personnel on cadavers before the devices can be used in patients. Postmortem circulation, a technique used for postmortem angiography, allows the vascular system to be reperfused in a way similar to that in living persons. This technique is used for postmortem investigations to visualize the human vascular system and to make vascular diagnoses. Specific material for reperfusing a human body was developed recently. Our aim was to investigate whether postmortem circulation that imitates in vivo conditions allows for the testing of medical materials on cadavers. We did this by delivering an aortic valve using minimally invasive methods. Postmortem circulation was established in eight corpses to recreate an environment as close as possible to in vivo conditions. Mobile fluoroscopy and a percutaneous catheterization technique were used to deliver the material to the correct place. Once the valve was implanted, the heart and primary vessels were extracted to confirm its position. Postmortem circulation proved to be essential in several of the cadavers because it helped the clinicians to deliver the material and improve their implantation techniques. Due to the intravascular circulation, sites with substantial arteriosclerotic stenosis could be bypassed, which would have been impossible without perfusion. Although originally developed for postmortem investigations, this reperfusion technique could be useful for testing new medical devices intended for living patients.