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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

Exploring high pressure nebulization of Pluronic F127 hydrogels for intraperitoneal drug delivery.

Peritoneal metastasis is an advanced cancer type which can be treated with pressurized intraperitoneal aerosol chemotherapy (PIPAC). Here, chemotherapeutics are nebulized under high pressure in the intraperitoneal (IP) cavity to obtain a better biodistribution and tumor penetration. To prevent the fast leakage of chemotherapeutics from the IP cavity, however, nebulization of controlled release formulations is of interest. In this study, the potential of the thermosensitive hydrogel Pluronic F127 to be applied by high pressure nebulization is evaluated. Therefore, aerosol formation is experimentally examined by laser diffraction and theoretically simulated by computational fluid dynamics (CFD) modelling. Furthermore, Pluronic F127 hydrogels are subjected to rheological characterization after which the release of fluorescent model nanoparticles from the hydrogels is determined. A delicate equilibrium is observed between controlled release properties and suitability for aerosolization, where denser hydrogels (20% and 25% w/v Pluronic F127) are able to sustain nanoparticle release up to 30 h, but cannot effectively be nebulized and vice versa. This is demonstrated by a growing aerosol droplet size and exponentially decreasing aerosol cone angle when Pluronic F127 concentration and viscosity increase. Novel nozzle designs or alternative controlled release formulations could move intraperitoneal drug delivery by high pressure nebulization forward.

Cytosolic delivery of gadolinium via photoporation enables improved in vivo magnetic resonance imaging of cancer cells.

Longitudinal in vivo monitoring of transplanted cells is crucial to perform cancer research or to assess the treatment outcome of cell-based therapies. While several bio-imaging techniques can be used, magnetic resonance imaging (MRI) clearly stands out in terms of high spatial resolution and excellent soft-tissue contrast. However, MRI suffers from low sensitivity, requiring cells to be labeled with high concentrations of contrast agents. An interesting option is to label cells with clinically approved gadolinium chelates which generate a hyperintense MR signal. However, spontaneous uptake of the label via pinocytosis results in its endosomal sequestration, leading to quenching of the T1-weighted relaxation. To avoid this quenching effect, delivery of gadolinium chelates directly into the cytosol via electroporation or hypotonic cell swelling have been proposed. However, these methods are also accompanied by several drawbacks such as a high cytotoxicity, and changes in gene expression and phenotype. Here, we demonstrate that nanoparticle-sensitized laser induced photoporation forms an attractive alternative to efficiently deliver the contrast agent gadobutrol into the cytosol of both HeLa and SK-OV-3 IP1 cells. After intracellular delivery by photoporation the quenching effect is clearly avoided, leading to a strong increase in the hyperintense T1-weighted MR signal. Moreover, when compared to nucleofection as a state-of-the-art electroporation platform, photoporation has much less impact on cell viability, which is extremely important for reliable cell tracking studies. Additional experiments confirm that photoporation does not induce any change in the long-term viability or the migratory capacity of the cells. Finally, we show that gadolinium 'labeled' SK-OV-3 IP1 cells can be imaged in vivo by MRI with high soft-tissue contrast and spatial resolution, revealing indications of potential tumor invasion or angiogenesis.

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.