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INTRODUCTION: Pancreatic neuroendocrine tumors (pNET) exhibit a wide spectrum of clinical behavior, which makes their assessment and management quite challenging. The purpose of this study was to comprehensively assess the existing treatment landscape for patients with pNET. MATERIALS AND METHODS: The study was conducted with the support of the ESSO-EYSAC Research Academy in collaboration with the E-AHPBA. An online survey was distributed via email and social media to surgical networks across Europe and beyond (September 1-30, 2023). RESULTS: Overall, 155 complete responses were obtained. A specialized NET tumor board was present at the institutions of 94 (61 %) of the study participants. The most frequently applied guidelines were from ENETS (n = 97; 63 %), NCCN (n = 74; 48 %), and ESMO (n = 53; 34 %). For resectability, similar criteria as in pancreatic ductal adenocarcinoma were used by 111 (72 %) participants, even though 116 (75 %) participants believed that pNET/pNEC should have their own resectability criteria. Most respondents used somatostatin analogues (n = 126; 81 %) and chemotherapy (n = 85; 55 %) as neoadjuvant treatments, followed by molecularly targeted agents (n = 45; 29 %) and PRRT (n = 37; 24 %). Only 17 (11 %) participants agreed/strongly agreed that the management of pNET/pNEC is sufficiently addressed in surgical education programs. CONCLUSION: This international survey highlighted areas for improvement in the care of pNET, namely the lack of pNET-specific resectability criteria and educational programs addressing pNET management.
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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.
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BACKGROUND AND PURPOSE: Postesophagectomy anastomotic leakage occurs in up to 16% of patients and is the main cause of morbidity and mortality. The leak severity is determined by the extent of contamination and the degree of sepsis, both of which are related to the time from onset to treatment. Early prediction based on inflammatory biomarkers such as C-reactive protein (CRP) levels, white blood cell counts, albumin levels, and combined Noble-Underwood (NUn) scores can guide early management. This review aimed to determine the diagnostic accuracy of these biomarkers. METHODS: This study was designed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines and registered in the PROSPERO (International Prospective Register of Systematic Reviews) database. Two reviewers independently conducted searches across PubMed, MEDLINE, Web of Science, and Embase. Sources of bias were assessed, and a meta-analysis was performed. RESULTS: Data from 5348 patients were analyzed, and 13% experienced leakage. The diagnostic accuracy of the serum biomarkers was analyzed, and pooled cutoff values were identified. CRP levels were found to have good diagnostic accuracy on days 2 to 5. The best discrimination was identified on day 2 for a cutoff value < 222 mg/L (area under the curve = 0.824, sensitivity = 81%, specificity = 88%, positive predictive value = 38.6%, and negative predictive value = 98%). A NUn score of >10 on day 4 correlated with poor diagnostic accuracy. CONCLUSION: The NUn score failed to achieve adequate accuracy. CRP seems to be the only valuable biomarker and is a negative predictor of postesophagectomy leakage. Patients with a CRP concentration of <222 mg/L on day 2 are unlikely to develop a leak, and patients can safely proceed through their enhanced recovery after surgery protocol. Patients with a CRP concentration of <127 mg/L on day 5 can be safely discharged when clinically possible.
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Anastomotic Leak , Biomarkers , C-Reactive Protein , Esophagectomy , Humans , Anastomotic Leak/blood , Anastomotic Leak/diagnosis , Anastomotic Leak/etiology , Biomarkers/blood , C-Reactive Protein/analysis , C-Reactive Protein/metabolism , Esophageal Neoplasms/surgery , Esophageal Neoplasms/blood , Esophagectomy/adverse effects , Leukocyte Count , Predictive Value of Tests , Serum Albumin/analysis , Serum Albumin/metabolism , Systemic Inflammatory Response Syndrome/blood , Systemic Inflammatory Response Syndrome/etiology , Systemic Inflammatory Response Syndrome/diagnosisABSTRACT
BACKGROUND: The anatomical pattern of lymph nodes spread differs between young (aged 45 years or younger) and elderly (aged 80 years or older) patients with stage III colon cancer and is poorly investigated. METHODS: Two groups of patients (young and elderly) with stage III colon cancer who underwent upfront extensive (D3) lymphadenectomy at eight Japanese centres between 1998 and 2018 were retrospectively analysed. The primary endpoint was the proportion of positive central lymph nodes. The lymph nodes spreading pattern and its prognostic impact on recurrence-free survival and overall survival in the two groups were also compared. RESULTS: Two hundred and ten young patients and 348 elderly patients were identified and compared. The total number of lymph nodes harvested and the total number of invaded lymph nodes were significantly higher in younger patients compared with elderly patients (median of 31.5 (3-151) versus 21 (3-116), P < 0.001 and median of 3 (1-21) versus 2 (1-25), P < 0.001 respectively). The proportion of positive central lymph nodes were higher in younger patients than in elderly patients (9.52% (95% c.i. 6.24 to 14.2%) versus 4.59% (95% c.i. 2.84 to 7.31%), P = 0.012). In multivariate models for recurrence-free survival, central lymph nodes invasion were identified as a poor prognostic factor in younger patients (HR 5.21 (95% c.i. 1.76 to 15.39)) but not in elderly patients (HR 1.73 (95% c.i. 0.80 to 3.76)). CONCLUSION: Young patients with stage III colon cancer have a higher risk of central lymph nodes invasion, suggesting a more aggressive disease biology. The presence of central lymph nodes invasion are associated with a worse outcome in young patients.
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Colonic Neoplasms , Lymph Node Excision , Lymph Nodes , Lymphatic Metastasis , Neoplasm Staging , Humans , Colonic Neoplasms/pathology , Colonic Neoplasms/mortality , Colonic Neoplasms/surgery , Female , Male , Middle Aged , Retrospective Studies , Aged, 80 and over , Lymphatic Metastasis/pathology , Lymph Nodes/pathology , Aged , Age Factors , Adult , Prognosis , Japan/epidemiology , Disease-Free SurvivalSubject(s)
Cisplatin , Hyperthermia, Induced , Ovarian Neoplasms , Peritoneal Neoplasms , Humans , Female , Ovarian Neoplasms/genetics , Ovarian Neoplasms/pathology , Cisplatin/therapeutic use , Peritoneal Neoplasms/secondary , Peritoneal Neoplasms/genetics , Peritoneal Neoplasms/drug therapy , Hyperthermia, Induced/methods , Antineoplastic Agents/therapeutic use , Hyperthermic Intraperitoneal Chemotherapy , Gene Expression , Combined Modality TherapyABSTRACT
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.
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Aerosols , Consensus , Delphi Technique , Patient Selection , Peritoneal Neoplasms , Humans , Peritoneal Neoplasms/drug therapy , Peritoneal Neoplasms/secondary , Antineoplastic Agents/administration & dosage , Infusions, Parenteral , Eligibility DeterminationABSTRACT
Background: Elevated tumor tissue interstitial fluid pressure (IFP) is an adverse biomechanical biomarker that predicts poor therapy response and an aggressive phenotype. Advances in functional imaging have opened the prospect of measuring IFP non-invasively. Image-based estimation of the IFP requires knowledge of the tissue hydraulic conductivity (K), a measure for the ease of bulk flow through the interstitium. However, data on the magnitude of K in human cancer tissue are not available. Methods: We measured the hydraulic conductivity of tumor tissue using modified Ussing chambers in surgical resection specimens. The effect of the tumor microenvironment (TME) on K was investigated by quantifying the collagen content, cell density, and fibroblast density of the tested samples using quantitative immune histochemistry. Also, we developed a computational fluid dynamics (CFD) model to evaluate the role of K on interstitial fluid flow and drug transport in solid tumors. Results: The results show that the hydraulic conductivity of human tumor tissues is very limited, ranging from approximately 10-15 to 10-14 m2/Paâs. Moreover, K values varied significantly between tumor types and between different samples from the same tumor. A significant inverse correlation was found between collagen fiber density and hydraulic conductivity values. However, no correlation was detected between K and cancer cell or fibroblast densities. The computational model demonstrated the impact of K on the interstitial fluid flow and the drug concentration profile: higher K values led to a lower IFP and deeper drug penetration. Conclusions: Human tumor tissue is characterized by a very limited hydraulic conductivity, representing a barrier to effective drug transport. The results of this study can inform the development of realistic computational models, facilitate non-invasive IFP estimation, and contribute to stromal targeting anticancer therapies.
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Anastomotic leakage (AL) remains the main cause of post-esophagectomy morbidity and mortality. Early detection can avoid sepsis and reduce morbidity and mortality. This study evaluates the diagnostic accuracy of the Nun score and its components as early detectors of AL. This single-center observational cohort study included all esophagectomies from 2010 to 2020. C-reactive protein (CRP), albumin (Alb), and white cell count (WCC) were analyzed and NUn scores were calculated. The area under the curve statistic (AUC) was used to assess their predictive accuracy. A total of 74 of the 668 patients (11%) developed an AL. CRP and the NUn-score proved to be good diagnostic accuracy tests on postoperative day (POD) 2 (CRP AUC: 0.859; NUn score AUC: 0.869) and POD 4 (CRP AUC: 0.924; NUn score AUC: 0.948). A 182 mg/L CRP cut-off on POD 4 yielded a 87% sensitivity, 88% specificity, a negative predictive value (NPV) of 98%, and a positive predictive value (PPV) of 47.7%. A NUn score cut-off > 10 resulted in 92% sensitivity, 95% specificity, 99% NPV, and 68% PPV. Albumin and WCC have limited value in the detection of post-esophagectomy AL. Elevated CRP and a high NUn score on POD 4 provide high accuracy in predicting AL after esophageal cancer surgery. Their high negative predictive value allows to select patients who can safely proceed with enhanced recovery protocols.
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Background: Epithelial ovarian cancer is associated with high mortality due to diagnosis at later stages associated with peritoneal involvement. Several trials have evaluated the effect of intraperitoneal treatment. In this preclinical study, we report the efficacy, pharmacokinetics and pharmacodynamics of intraperitoneal treatment with two approved nanomolecular formulations of paclitaxel (nab-PTX and mic-PTX) in a murine ovarian cancer xenograft model. Methods: IC50 was determined in vitro on three ovarian cancer cell lines (OVCAR-3, SK-OV-3 and SK-OV-3-Luc IP1). EOC xenografts were achieved using a modified subperitoneal implantation technique. Drug treatment was initiated 2 weeks after engraftment, and tumor volume and survival were assessed. Pharmacokinetics and drug distribution effects were assessed using UHPLC-MS/MS and MALDI imaging mass spectrometry, respectively. Pharmacodynamic effects were analyzed using immunohistochemistry and transmission electron microscopy using standard protocols. Results: We demonstrated sub-micromolar IC50 concentrations for both formulations on three EOC cancer cell lines in vitro. Furthermore, IP administration of nab-PTX or mic-PTX lead to more than 2-fold longer survival compared to a control treatment of IP saline administration (30 days in controls, 66 days in nab-PTX treated animals, and 76 days in mic-PTX animals, respectively). We observed higher tissue uptake of drug following nab-PTX administration when compared to mic-PTX, with highest uptake after 4 hours post-treatment, and confirmed this lower uptake of mic-PTX using HPLC on digested tumor samples. Furthermore, apoptosis was not increased in tumor implants up to 24h post-treatment. Conclusion: Intraperitoneal administration of both nab-PTX and mic-PTX results in a significant anticancer efficacy and survival benefit in a mouse OC xenograft model.
Subject(s)
Ovarian Neoplasms , Humans , Animals , Female , Mice , Ovarian Neoplasms/drug therapy , Paclitaxel/pharmacology , Heterografts , Apoptosis , Tandem Mass Spectrometry , Cell Line, Tumor , Disease Models, AnimalABSTRACT
Irinotecan (CPT-11), an antineoplastic drug, is used for the treatment of colorectal and pancreatic cancer due to its topoisomerase I inhibitory activity. CPT-11 is a prodrug which is converted to its active metabolite SN-38 by carboxylesterases. SN-38 is further metabolized to its inactive metabolite SN-38 glucuronide. When evaluating the pharmacokinetic properties of CPT-11 and its metabolites, it is important to accurately assess the concentrations in both plasma as well as tumor tissues. Therefore, the aim of the current study was to develop and validate a robust and sensitive ultra-high performance liquid chromatography-tandem mass spectrometry method to quantify the concentration of CPT-11 and its metabolites (SN-38 and SN-38 glucuronide) in human plasma and peritoneal tumor tissue. The sample preparation of plasma and tumor tissue consisted of protein precipitation and enzymatic digestion/liquid-liquid extraction, respectively. Chromatographic separation was achieved with an Acquity UPLC BEH C18 column combined with a VanGuard pre-column. The mobile phases consisted of water +0.1 % formic acid (mobile phase A) and acetonitrile +0.1 % formic acid (mobile phase B). Mass analysis was performed using a Xevo TQS tandem mass spectrometer in the positive electrospray ionization mode. Method validation was successfully performed by assessing linearity, precision and accuracy, lower limit of quantification, carry over, selectivity, matrix effect and stability according to the following guidelines: "Committee for Medicinal Products for Human use, Guideline on Bioanalytical Method Validation". A cross-validation of the developed method was performed in a pilot pharmacokinetic study, demonstrating the usefulness of the current method to quantify CPT-11 and its metabolites in the different matrices.
Subject(s)
Camptothecin/analogs & derivatives , Formates , Glucuronides , Peritoneal Neoplasms , Humans , Irinotecan , Tandem Mass Spectrometry/methods , Chromatography, Liquid/methods , Liquid Chromatography-Mass Spectrometry , Chromatography, High Pressure Liquid/methods , Reproducibility of ResultsABSTRACT
BACKGROUND: Long-term drug evaluation heavily relies upon rodent models. Drug discovery methods to reduce animal models in oncology may include three-dimensional (3D) cellular systems that take into account tumor microenvironment (TME) cell types and biomechanical properties. METHODS: In this study we reconstructed a 3D tumor using an elastic polymer (acrylate-endcapped urethane-based poly(ethylene glycol) (AUPPEG)) with clinical relevant stiffness. Single cell suspensions from low-grade serous ovarian cancer (LGSOC) patient-derived early passage cultures of cancer cells and cancer-associated fibroblasts (CAF) embedded in a collagen gel were introduced to the AUPPEG scaffold. After self-organization in to a 3D tumor, this model was evaluated by a long-term (> 40 days) exposure to a drug combination of MEK and HSP90 inhibitors. The drug-response results from this long-term in vitro model are compared with drug responses in an orthotopic LGSOC xenograft mouse model. RESULTS: The in vitro 3D scaffold LGSOC model mimics the growth ratio and spatial organization of the LGSOC. The AUPPEG scaffold approach allows to test new targeted treatments and monitor long-term drug responses. The results correlate with those of the orthotopic LGSOC xenograft mouse model. CONCLUSIONS: The mechanically-tunable scaffolds colonized by a three-dimensional LGSOC allow long-term drug evaluation and can be considered as a valid alternative to reduce, replace and refine animal models in drug discovery.
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Because peritoneal metastasis (PM) from ovarian cancer is characterized by non-specific symptoms, it is often diagnosed at advanced stages. Pressurized intraperitoneal aerosol chemotherapy (PIPAC) can be considered a promising drug delivery method for unresectable PM. Currently, the efficacy of intraperitoneal (IP) drug delivery is limited by the off-label use of IV chemotherapeutic solutions, which are rapidly cleared from the IP cavity. Hence, this research aimed to improve PM treatment by evaluating a nanoparticle-loaded, pH-switchable supramolecular polymer hydrogel as a controlled release drug delivery system that can be IP nebulized. Moreover, a multidirectional nozzle was developed to allow nebulization of viscous materials such as hydrogels and to reach an even IP gel deposition. We demonstrated that acidification of the nebulized hydrogelator solution by carbon dioxide, used to inflate the IP cavity during laparoscopic surgery, stimulated the in situ gelation, which prolonged the IP hydrogel retention. In vitro experiments indicated that paclitaxel nanocrystals were gradually released from the hydrogel depot formed, which sustained the cytotoxicity of the formulation for 10 days. Finally, after aerosolization of this material in a xenograft model of PM, tumor progression could successfully be delayed, while the overall survival time was significantly increased compared to non-treated animals.
Subject(s)
Carbon Dioxide , Peritoneal Neoplasms , Animals , Humans , Peritoneal Neoplasms/drug therapy , Hydrogels/chemistry , Polymers/chemistry , Hydrogen-Ion ConcentrationABSTRACT
Hyperthermia combined with intraperitoneal (IP) drug delivery is increasingly used in the treatment of peritoneal metastases (PM). Hyperthermia enhances tumor perfusion and increases drug penetration after IP delivery. The peritoneum is increasingly recognized as an immune-privileged organ with its own distinct immune microenvironment. Here, we review the immune landscape of the healthy peritoneal cavity and immune contexture of peritoneal metastases. Next, we review the potential benefits and unwanted tumor-promoting effects of hyperthermia and the associated heat shock response on the tumor immune microenvironment. We highlight the potential modulating effect of hyperthermia on the biomechanical properties of tumor tissue and the consequences for immune cell infiltration. Data from translational and clinical studies are reviewed. We conclude that (mild) hyperthermia and HIPEC have the potential to enhance antitumor immunity, but detailed further studies are required to distinguish beneficial from tumor-promoting effects.
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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.
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Postoperative peritoneal adhesions occur in the majority of patients undergoing intra-abdominal surgery and are one of the leading causes of hospital re-admission. There is an unmet clinical need for effective anti-adhesive biomaterials, which can be applied evenly across the damaged tissues. We examined three different responsive hydrogel types, i.e. a thermosensitive PLGA-PEG-PLGA, a pH responsive UPy-PEG and a shear-thinning hexapeptide for this purpose. More specifically, their potential to be homogeneously distributed in the peritoneal cavity by high pressure nebulization and prevent peritoneal adhesions was evaluated. Solutions of each polymer type could be successfully nebulized while retaining their responsive gelation behavior in vitro and in vivo. Furthermore, none of the polymers caused in vitro toxicity on SKOV3-IP2 cells. Following intraperitoneal administration, both the PLGA-PEG-PLGA and the hexapeptide hydrogels resulted in local inflammation and fibrosis and failed in preventing peritoneal adhesions 7 days after adhesion induction. In contrast, the pH sensitive UPy-PEG formulation was well tolerated and could significantly reduce the formation of peritoneal adhesions, even outperforming the commercially available Hyalobarrier® as positive control. To conclude, local nebulization of the bioresponsive UPy-PEG hydrogel can be considered as a promising approach to prevent postsurgical peritoneal adhesions.
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Inadequate uptake of therapeutic agents by tumor cells is still a major barrier in clinical cancer therapy. Mathematical modeling is a powerful tool to describe and investigate the transport phenomena involved. However, current models for interstitial flow and drug delivery in solid tumors have not yet embedded the existing heterogeneity of tumor biomechanical properties. The purpose of this study is to introduce a novel and more realistic methodology for computational models of solid tumor perfusion and drug delivery accounting for these regional heterogeneities as well as lymphatic drainage effects. Several tumor geometries were studied using an advanced computational fluid dynamics (CFD) modeling approach of intratumor interstitial fluid flow and drug transport. Hereby, the following novelties were implemented: (i) the heterogeneity of tumor-specific hydraulic conductivity and capillary permeability; (ii) the effect of lymphatic drainage on interstitial fluid flow and drug penetration. Tumor size and shape both have a crucial role on the interstitial fluid flow regime as well as drug transport illustrating a direct correlation with interstitial fluid pressure (IFP) and an inverse correlation with drug penetration, except for large tumors having a diameter larger than 50 mm. The results also suggest that the interstitial fluid flow and drug penetration in small tumors depend on tumor shape. A parameter study on the necrotic core size illustrated that the core effect (i.e. fluid flow and drug penetration alteration) was only profound in small tumors. Interestingly, the impact of a necrotic core on drug penetration differs depending on the tumor shape from having no effect in ideally spherical tumors to a clear effect in elliptical tumors with a necrotic core. A realistic presence of lymphatic vessels only slightly affected tumor perfusion, having no substantial effect on drug delivery. In conclusion, our findings illustrated that our novel parametric CFD modeling strategy in combination with accurate profiling of heterogeneous tumor biophysical properties can provide a powerful tool for better insights into tumor perfusion and drug transport, enabling effective therapy planning.
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Neoplasms , Humans , Neoplasms/pathology , Biological Transport , Models, Theoretical , Drug Delivery Systems , Extracellular FluidABSTRACT
INTRODUCTION: Malnutrition is common in patients suffering from malignant diseases and has a major impact on patient outcomes. Prevention and early detection are crucial for effective treatment. This study aimed to investigate current international practice in the assessment and management of malnutrition in surgical oncology departments. MATERIAL AND METHODS: The survey was designed by European Society of Surgical Oncology (ESSO) and ESSO Young Surgeons and Alumni Club (EYSAC) Research Academy as an online questionnaire with 41 questions addressing three main areas: participant demographics, malnutrition assessment, and perioperative nutritional standards. The survey was distributed from October to November 2021 via emails, social media and the ESSO website to surgical networks focussing on surgical oncologists. Results were collected and analysed by an independent team. RESULTS: A total of 156 participants from 39 different countries answered the survey, reflecting a response rate of 1.4%. Surgeons reported treating a mean of 22.4 patients per month. 38% of all patients treated in surgical oncology departments were routinely screened for malnutrition. 52% of patients were perceived as being at risk for malnutrition. The most used screening tool was the "Malnutrition Universal Screening Tool" (MUST). 68% of participants agreed that the surgeon is responsible for assessing preoperative nutritional status. 49% of patients were routinely seen by dieticians. In cases of severe malnutrition, 56% considered postponing the operation. CONCLUSIONS: The reported rate of malnutrition screening by surgical oncologists is lower than expected (38%). This indicates a need for improved awareness of malnutrition in surgical oncology, and nutritional screening.