Use of 3D Prototypes for Complex Surgical Oncologic Cases

Introduction: Physical 3D models known by the industry as rapid prototyping involve the creation of a physical model from a 3D computer version. In recent years, there has been an increasing number of reports on the use of 3D models in medicine. Printing such 3D models with different materials integrating the many components of human anatomy is technically challenging. In this article, we report our technological developments along with our clinical implementation experience using high-fidelity 3D prototypes of tumors encasing major vessels in anatomically sensitive areas. Methods: Three patients with tumors encasing major vessels that implied complex surgery were selected for surgical planning using 3D prototypes. 3D virtual models were obtained from routine CT and MRI images. The models, with all their anatomical relations, were created by an expert pediatric radiologist and a surgeon, image by image, along with a computerized-aided design engineer. Results: Surgeons had the opportunity to practice on the model before the surgery. This allowed questions regarding surgical approach; feasibility and potential complications to be raised in advance of the actual procedure. All patients then successfully underwent surgery as planned. Conclusion: Having a tumor physically printed in its different main component parts with its anatomical relationships is technically feasible. Since a gross total resection is prognostic in a significant percentage of tumor types, refinements in planning may help achieve greater and safer resections therefore contributing to improve surgical management of complex tumors. In this early experience, 3D prototyping helped significantly in the many aspects of surgical oncology planning

Developing tuneable viscoelastic silicone gel-based inks for precise 3D printing of clinical phantoms

Tissue and organ phantoms with realistic anatomical features are becoming increasingly popular in the medical field due to their potential to revolutionize surgical planning and practice. Despite advancements in the production technology using 3D printing and development of materials, the availability of 3D printable materials that accurately replicate human organs’ mechanical properties is limited. Therefore, we developed a family of silicone gel-based inks that can be 3D printed using direct ink writing (DIW) with tuneable viscoelastic properties that mimic a wide range of soft tissues. The control over viscoelastic properties is achieved by fine tuning of silicone formulations with a rheology modifier to promote the encapsulating silicone oil. This strategy not only allows for the recreation of the viscoelastic behaviour profile of a wide range of soft tissues through amplitude and frequency sweeps but also is entirely compatible with DIW printing for medical model manufacturing. Thus, this study stands as one of the few in the literature presenting a DIW printing technology enabling the printing of silicone with such precise control over viscoelastic properties that it allows for different sensations to be experienced by the evaluating medical team.Peer ReviewedPostprint (published version

Cysteine and Folate metabolism are targetable vulnerabilities of metastatic colorectal cancer

With most cancer-related deaths resulting from metastasis, the development of new therapeutic approaches against metastatic colorectal cancer (mCRC) is essential to increasing patient survival. The metabolic adaptations that support mCRC remain undefined and their elucidation is crucial to identify potential therapeutic targets. Here, we employed a strategy for the rational identification of targetable metabolic vulnerabilities. This strategy involved first a thorough metabolic characterisation of same-patient-derived cell lines from primary colon adenocarcinoma (SW480), its lymph node metastasis (SW620) and a liver metastatic derivative (SW620-LiM2), and second, using a novel multi-omics integration workflow, identification of metabolic vulnerabilities specific to the metastatic cell lines. We discovered that the metastatic cell lines are selectively vulnerable to the inhibition of cystine import and folate metabolism, two key pathways in redox homeostasis. Specifically, we identified the system xCT and MTHFD1 genes as potential therapeutic targets, both individually and combined, for combating mCRC

Effects of a paediatric antimicrobial stewardship program on antimicrobial use and quality of prescriptions in patients with appendix-related intraabdominal infections

The effectiveness of antimicrobial stewardship programs (ASP) in reducing antimicrobial use (AU) in children has been proved. Many interventions have been described suitable for different institution sizes, priorities, and patients, with surgical wards being one of the areas that may benefit the most. We aimed to describe the results on AU and length of stay (LOS) in a pre-post study during the three years before (2014-2016) and the three years after (2017-2019) implementation of an ASP based on postprescription review with feedback in children and adolescents admitted for appendix-related intraabdominal infections (AR-IAI) in a European Referral Paediatric University Hospital. In the postintervention period, the quality of prescriptions (QP) was also evaluated. Overall, 2021 AR-IAIs admissions were included. Global AU, measured both as days of therapy/100 patient days (DOT/100PD) and length of therapy (LOT), and global LOS remained unchanged in the postintervention period. Phlegmonous appendicitis LOS (p = 0.003) and LOT (p < 0.001) significantly decreased, but not those of other AR-IAI diagnoses. The use of piperacillin-tazobactam decreased by 96% (p = 0.044), with no rebound in the use of other Gram-negative broad-spectrum antimicrobials. A quasisignificant (p = 0.052) increase in QP was observed upon ASP implementation. Readmission and case fatality rates remained stable. ASP interventions were safe, and they reduced LOS and LOT of phlegmonous appendicitis and the use of selected broad-spectrum antimicrobials, while increasing QP in children with AR-IAI

Effects of pre-operative isolation on postoperative pulmonary complications after elective surgery: an international prospective cohort study

We aimed to determine the impact of pre-operative isolation on postoperative pulmonary complications after elective surgery during the global SARS-CoV-2 pandemic. We performed an international prospective cohort study including patients undergoing elective surgery in October 2020. Isolation was defined as the period before surgery during which patients did not leave their house or receive visitors from outside their household. The primary outcome was postoperative pulmonary complications, adjusted in multivariable models for measured confounders. Pre-defined sub-group analyses were performed for the primary outcome. A total of 96,454 patients from 114 countries were included and overall, 26,948 (27.9%) patients isolated before surgery. Postoperative pulmonary complications were recorded in 1947 (2.0%) patients of which 227 (11.7%) were associated with SARS-CoV-2 infection. Patients who isolated pre-operatively were older, had more respiratory comorbidities and were more commonly from areas of high SARS-CoV-2 incidence and high-income countries. Although the overall rates of postoperative pulmonary complications were similar in those that isolated and those that did not (2.1% vs 2.0%, respectively), isolation was associated with higher rates of postoperative pulmonary complications after adjustment (adjusted OR 1.20, 95%CI 1.05-1.36, p = 0.005). Sensitivity analyses revealed no further differences when patients were categorised by: pre-operative testing; use of COVID-19-free pathways; or community SARS-CoV-2 prevalence. The rate of postoperative pulmonary complications increased with periods of isolation longer than 3 days, with an OR (95%CI) at 4-7 days or ≥ 8 days of 1.25 (1.04-1.48), p = 0.015 and 1.31 (1.11-1.55), p = 0.001, respectively. Isolation before elective surgery might be associated with a small but clinically important increased risk of postoperative pulmonary complications. Longer periods of isolation showed no reduction in the risk of postoperative pulmonary complications. These findings have significant implications for global provision of elective surgical care

Mortality from gastrointestinal congenital anomalies at 264 hospitals in 74 low-income, middle-income, and high-income countries: a multicentre, international, prospective cohort study

Summary Background Congenital anomalies are the fifth leading cause of mortality in children younger than 5 years globally. Many gastrointestinal congenital anomalies are fatal without timely access to neonatal surgical care, but few studies have been done on these conditions in low-income and middle-income countries (LMICs). We compared outcomes of the seven most common gastrointestinal congenital anomalies in low-income, middle-income, and high-income countries globally, and identified factors associated with mortality. Methods We did a multicentre, international prospective cohort study of patients younger than 16 years, presenting to hospital for the first time with oesophageal atresia, congenital diaphragmatic hernia, intestinal atresia, gastroschisis, exomphalos, anorectal malformation, and Hirschsprung’s disease. Recruitment was of consecutive patients for a minimum of 1 month between October, 2018, and April, 2019. We collected data on patient demographics, clinical status, interventions, and outcomes using the REDCap platform. Patients were followed up for 30 days after primary intervention, or 30 days after admission if they did not receive an intervention. The primary outcome was all-cause, in-hospital mortality for all conditions combined and each condition individually, stratified by country income status. We did a complete case analysis. Findings We included 3849 patients with 3975 study conditions (560 with oesophageal atresia, 448 with congenital diaphragmatic hernia, 681 with intestinal atresia, 453 with gastroschisis, 325 with exomphalos, 991 with anorectal malformation, and 517 with Hirschsprung’s disease) from 264 hospitals (89 in high-income countries, 166 in middleincome countries, and nine in low-income countries) in 74 countries. Of the 3849 patients, 2231 (58·0%) were male. Median gestational age at birth was 38 weeks (IQR 36–39) and median bodyweight at presentation was 2·8 kg (2·3–3·3). Mortality among all patients was 37 (39·8%) of 93 in low-income countries, 583 (20·4%) of 2860 in middle-income countries, and 50 (5·6%) of 896 in high-income countries (p<0·0001 between all country income groups). Gastroschisis had the greatest difference in mortality between country income strata (nine [90·0%] of ten in lowincome countries, 97 [31·9%] of 304 in middle-income countries, and two [1·4%] of 139 in high-income countries; p≤0·0001 between all country income groups). Factors significantly associated with higher mortality for all patients combined included country income status (low-income vs high-income countries, risk ratio 2·78 [95% CI 1·88–4·11], p<0·0001; middle-income vs high-income countries, 2·11 [1·59–2·79], p<0·0001), sepsis at presentation (1·20 [1·04–1·40], p=0·016), higher American Society of Anesthesiologists (ASA) score at primary intervention (ASA 4–5 vs ASA 1–2, 1·82 [1·40–2·35], p<0·0001; ASA 3 vs ASA 1–2, 1·58, [1·30–1·92], p<0·0001]), surgical safety checklist not used (1·39 [1·02–1·90], p=0·035), and ventilation or parenteral nutrition unavailable when needed (ventilation 1·96, [1·41–2·71], p=0·0001; parenteral nutrition 1·35, [1·05–1·74], p=0·018). Administration of parenteral nutrition (0·61, [0·47–0·79], p=0·0002) and use of a peripherally inserted central catheter (0·65 [0·50–0·86], p=0·0024) or percutaneous central line (0·69 [0·48–1·00], p=0·049) were associated with lower mortality. Interpretation Unacceptable differences in mortality exist for gastrointestinal congenital anomalies between lowincome, middle-income, and high-income countries. Improving access to quality neonatal surgical care in LMICs will be vital to achieve Sustainable Development Goal 3.2 of ending preventable deaths in neonates and children younger than 5 years by 2030

Correlació entre l’hemodinàmica, la morfometria, la histoquímica i l’estat neonatal en un model d’hipoplàsia pulmonar per hèrnia diafragmàtica congènita

[cat] OBJETIUS: Estudiar diversos aspectes (hemodinàmics, morfològics, histoquímics i funcionals) de la hipoplàsia pulmonar (HP) en un model animal d’hèrnia diafragmàtica congènita (HDC). DISENY: Estudi experimental en conill Neozelandès blanc. GRUPS: Hèrnia diafragmàtica (HD); Control (C). INTERVENCIONS: Cirurgia intraúter el dia 23 de gestació, practicant una HD i avaluació hemodinàmica amb eco-doppler. Reintervenció el dia 28 de gestació, amb una nova avaluació hemodinàmica. Extracció dels fetus per cesària el dia 30 de gestació (gestació completa: 31 dies), i nova avaluació hemodinàmica. Canulació de la tràquea dels nounats i col·locació sota campana d’O2 durant 1 hora. Necròpsia, extracció i processat de les mostres de pulmó. DETERMINACIONS: Hemodinàmiques: Fluxometria de l’artèria pulmonar (PI i FMBV). Morfològiques: pes pulmonar (PP); Relació Pes Pulmó/Pes Corporal (LBWR); morfometria vascular pulmonar (GPA); recompte alveolar radial (RAC). Inmunohistoquímiques: Determinació de FGF-10, TGF-β, VEGF i PDGF-A. Funcionales: SaO2 a FiO2 de 0,21 a l’hora de vida. Estadística: Proves no paramètriques de les variables quantitatives; descripció de les variables qualitatives. RESULTATS: En el grup HD tots els paràmetres hemodinàmics i morfomètrics han estat significativament pitjors que en el grup C. La mortalitat neonatal en la 1a hora va ser del 66% i 7% respectivament en els grups HD i C. Les dades hemodinàmiques es correlacionen estretament amb les morfològiques. CONCLUSIONS: 1. Aquest model d’HD és válid per a l’estudi de l’HDC ja que produeix: a) Una significativa HP segons els paràmetres morfològics (PP, LBWR i RAC). b) Una significativa alteració morfològica (GPA) de les arterioles pulmonars característica de la hipertensió pulmonar. c) Una insuficiència respiratòria neonatal que es manifesta en els paràmetres clínics (SaO2, FC, mortalitat en la 1a hora). d) La seqüència fisiopatològica esperada: hèrnia diafragmàtica, hipoplàsia pulmonar, hipertensió pulmonar amb hipoperfusió pulmonar i insuficiència respiratòria neonatal. 2. Aquest model quirúrgic d’HD permet avaluar la circulació pulmonar fetal amb eco-doppler, que és sensible per a detectar el significatiu augment de resistència vascular i disminució de la perfusió pulmonar que presenten els fetus amb HD. 3. En aquest model d’HD l’índex de pulsatilitat (PI) i la fracció de sang en moviment (FMBV) determinats per eco-doppler mesuren prenatalmente el grau d’hipoplàsia pulmonar.[eng] OBJECTIVES: To study various features (hemodynamic, morphological, hystochemical and functional) of pulmonary hypoplasia (HP) in an animal model of congenital diaphragmatic hernia (HD). DESIGN: Experimental study in New Zealand white rabbits. GROUPS: diaphragmatic hernia (HD); Control (C). SURGERY: Fetal surgery on day 23 of gestation, performing an HD and hemodynamic assessment with eco-doppler. Reoperation on day 28 of gestation, with a new hemodynamic assessment. Fetus extraction by Caesarean section on day 30 of gestation (pregnancy completes at 31 days) and hemodynamic reassessment. Cannulation of the newborn’s trachea and placement under O2 hood for 1 hour. Necropsy, extraction and processing the samples of lung tissue. DETERMINATIONS: Hemodynamic: Fluxometry of the pulmonary artery (PI: Pulsatility Index, and FMBV: Fractional Moving Blood Volume). Morphological: lung weight (PP); Lung –to-body weight ratio (LBWR); pulmonary vascular morphometry (GPA); radial alveolar count (RAC). Immunohystochemical: Determination of FGF-10, TGF-β, PDGF and VEGF-A. Functional: SaO2 with 0.21 FiO2 at one hour of life. Statistics: nonparametric tests of quantitative variables; description of qualitative variables. RESULTS: In the HD group all hemodynamic and morphometric parameters were significantly worse than in group C. The neonatal mortality in the 1st hour was 66% and 7% respectively in groups HD and C. The hemodynamic data closely correlate with morphology. CONCLUSIONS: 1. The HD model is valid for the study of HDC since it produces: a) A significant HP according to morphological parameters (PP, LBWR and RAC). b) A significant morphological change (GPA) of the pulmonary arterioles characteristic of pulmonary hypertension. c) A neonatal respiratory insufficiency proved by clinical parameters(SaO2, FC, mortality in the 1st hour). d) An expected pathophysiological sequence: diaphragmatic hernia, pulmonary hypoplasia, pulmonary hypertension with pulmonary hypoperfusion and neonatal respiratory failure. 2. This surgical model of HD enables to assess fetal pulmonary circulation with Doppler ultrasound, which is sensitive to detect a significant increase in vascular resistance and decreased pulmonary perfusion found in fetuses with HD. 3. In this HD model, the pulsatility index (PI) and the fractional moving blood volume (FMBV) determined by Doppler ultrasound measure the degree of pulmonary hypoplasia prenatally