Variations in the definition and perceived importance of positive resection margins in patients with colorectal cancer - an EYSAC international survey.

INTRODUCTION: Microscopically positive resection margins (R1) are associated with poorer outcomes in patients with colorectal cancer. However, different definitions of R1 margins exist. It is unclear to what extent the definitions used in everyday clinical practice differ within and between nations. This study sought to investigate variations in the definition of R1 margins in colorectal cancer and the importance of margin status in clinical decision-making. MATERIALS AND METHODS: A 14-point survey was developed by members of The European Society of Surgical Oncology (ESSO) Youngs Surgeons and Alumni Club (EYSAC) Research Academy targeting all members of the multidisciplinary team (MDT) treating patients with colorectal cancer. The survey was distributed on social media, in ESSO's monthly newsletter and via national societies. RESULTS: In total, 137 responses were received. Most respondents were from Europe (89.7%), with the majority from Denmark (56.9%). Less than 2/3 of respondents defined R1 margins as the presence of viable cancer cells ≤1 mm of the margin. Only 60% reported that subdivisions of R1 margins (primary tumour vs tumour deposit vs metastatic lymph node) are routinely available. More than 20% of respondents reported that pathology reports are not routinely reviewed at MDT meetings. Less than half of respondents considered margin status in decision-making for type and duration of adjuvant chemotherapy in Stage III colon cancer. CONCLUSION: The definitions and perceived clinical importance of microscopically positive margins in patients with colorectal cancer appear to vary. Adoption of an international dataset for pathology reporting may help to standardise current practices.

Like Frying Multiple Eggs in One Pan: a Qualitative Study Exploring the Understanding of Inter-speciality Training in Cancer Care.

H igh-quality cancer care is a key priority worldwide. Caring for people affected by cancer requires a range of specific knowledge, skills and experience to deliver the complex care regimens both within the hospital and within the community environment. In June 2022, the European Cancer Organisation along with 33 European cancer societies began working together to develop a curriculum for inter-speciality training for healthcare professionals across Europe. As part of the project, this research consisted of a qualitative survey distributed to the European Union societies via email. The aim of this paper is to disseminate the qualitative findings from healthcare professionals across Europe. Questionnaires were sent out to a convenience sample of 219 healthcare professionals and patient advocates with a response rate of 55% (n = 115). The findings identified that there were four key themes: 'What is inter-speciality training?', 'Barriers and challenges', 'Support throughout the cancer journey' and 'New ways of working'. These results are part of a larger needs analysis and scoping review to inform the development of a core competency framework which will be part of an inter-speciality curriculum for specialist cancer doctors, nurses and other healthcare professionals across Europe. Healthcare professionals will be able to access education and training through the virtual learning environment and workshops and by clinical rotations to other specialties.

UNGAP best practice for improving solubility data quality of orally administered drugs.

An important goal of the European Cooperation in Science and Technology (COST) Action UNGAP (UNderstanding Gastrointestinal Absorption-related Processes, www.ungap.eu) is to improve standardization of methods relating to the study of oral drug absorption. Solubility is a general term that refers to the maximum achievable concentration of a compound dissolved in a liquid medium. For orally administered drugs, relevant information on drug properties is crucial during drug (product) development and at the regulatory level. Collection of reliable and reproducible solubility data requires careful application and understanding of the limitations of the selected experimental method. In addition, the purity of a compound and its solid state form, as well as experimental parameters such as temperature of experimentation, media related factors, and sample handling procedures can affect data quality. In this paper, an international consensus developed by the COST UNGAP network on recommendations for collecting high quality solubility data for the development of orally administered drugs is proposed.

Effect of oxaliplatin-based chemotherapy on chemosensitivity in patients with peritoneal metastasis from colorectal cancer treated with cytoreductive surgery and hyperthermic intraperitoneal chemotherapy: proof-of-concept study.

BACKGROUND: Chemosensitivity testing, including collagen gel droplet-embedded culture drug sensitivity test, has proven to be a useful tool in therapeutic decision-making. This retrospective analysis investigated chemosensitivity testing of peritoneal metastases collected during cytoreductive surgery (CRS), and its impact on survival in patients with colorectal cancer. METHODS: All patients with peritoneal metastasis from colorectal cancer who underwent CRS with or without hyperthermic intraperitoneal chemotherapy (HIPEC) between November 2008 and October 2014 were included. The growth inhibition rate was expressed as the ratio between the image density after treatment (T) and that before treatment (control, C). Tumours with a reduction in T/C ratio of less than 20 per cent were defined as resistant and those with a reduction of 20 per cent or more as sensitive. Groups were compared for overall (OS) and disease-free (DFS) survival. RESULTS: Of 84 eligible patients, 81 received neoadjuvant chemotherapy (NACT), including 56 patients with an oxaliplatin-based regimen. Mean(s.d.) follow-up was 23·4(22·9) months. The median overall survival of all patients was 19·0 (i.q.r. 5·7-36·1) months, with a progression-free survival time of 10·1 (4·5-17·0) months. Patients who received oxaliplatin-based NACT had significantly altered chemosensitivity to oxaliplatin; only 20 of 51 such patients showed chemosensitivity to oxaliplatin compared with 16 of 24 who did not undergo oxaliplatin-based NACT (P = 0·046). However, patients who showed chemoresistance to oxaliplatin had similar OS to those with chemosensitivity (18·8 versus 18·1 months; P = 0·835). The choice of HIPEC agents in patients who received oxaliplatin-based NACT did not significantly influence survival (oxaliplatin versus mitomycin C: median OS 20·6 (10·9-24·8) versus 19·0 (10·5-34·6) months, P = 0·811; DFS 6·6 (2·8-25·7) versus 9·3 (4·1-13·9) months, P = 0·191). CONCLUSION: Patients who had oxaliplatin-based NACT showed a higher rate of chemoresistance to oxaliplatin at the time of CRS and HIPEC. The impact of chemosensitivity testing on OS remains unclear and needs further investigation.

Clinical and surgical outcomes of patients with peritoneal mesothelioma discussed at a monthly national multidisciplinary team video-conference meeting.

BACKGROUND: Peritoneal mesothelioma (PM) is a rare primary neoplasm of the peritoneum with an increasing incidence worldwide. Cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC) has shown promise as a treatment strategy. A national PM multidisciplinary team (national PM MDT) video-conference meeting was established in the UK and Ireland in March 2016, aiming to plan optimal treatment, record outcomes and provide evidence for the benefits of centralization. This article reports on the activities and outcomes of the first 2·5 years. METHODS: Between March 2016 and December 2018, patients with PM, referred to peritoneal malignancy centres in Basingstoke, Birmingham, Manchester and Dublin, were discussed by the national PM MDT via video-conference. The MDT was composed of surgeons, radiologists, specialist nurses and pathologists. Patients were considered for CRS and HIPEC if considered fit for surgery and if radiological imaging suggested that complete surgical cytoreduction could be achieved. Morbidity and mortality following surgery were analysed. Survival analysis following MDT discussion was conducted. RESULTS: A total of 155 patients (M : F ratio 0·96) with a mean(s.d.) age of 57(17) years were discussed. To date, 22 (14·2 per cent) have had CRS and HIPEC; the median Peritoneal Cancer Index for the surgical group was 17·0. Complete cytoreduction was achieved in 19 patients. Clavien-Dindo grade I-II complications occurred in 16 patients; there was no grade III-IV morbidity or 30-day in-hospital mortality. The median follow-up for the whole cohort was 18·7 months, and the 2-year survival rate from time of first review at the national PM MDT was 68·3 per cent. CONCLUSION: The centralized national PM MDT was effective at selecting patients suitable for CRS and HIPEC, reporting a good outcome from patient selection.

ANTECEDENTES: El mesotelioma peritoneal (peritoneal mesothelioma, PM) es una neoplasia primaria del peritoneo muy poco frecuente, con una incidencia creciente en todo el mundo. La cirugía citorreductora (cytoreductive surgery, CRS) con quimioterapia intraperitoneal hipertérmica (hyperthermic intraperitoneal chemotherapy, HIPEC) se ha mostrado prometedora como estrategia de tratamiento. En marzo de 2016, se organizó una reunión por videoconferencia del equipo multidisciplinar nacional de PM (national PM multi-Disciplinary Team, MDT) en el Reino Unido e Irlanda, con el objetivo de planificar un tratamiento óptimo, registrar los resultados y proporcionar evidencia de los beneficios de la centralización. Este manuscrito presenta las actividades y los resultados de los primeros 2,5 años. MÉTODOS: Entre marzo de 2016 y diciembre de 2018, 155 pacientes con PM, remitidos a centros de cirugía oncológica peritoneal en Basingstoke, Good Hope Hospital en Birmingham, Christie Hospital en Manchester y Mater Misericordiae en Dublín, fueron discutidos en el National PM MDT a través de una videoconferencia. El MDT estaba compuesto por cirujanos, radiólogos, enfermeras especializadas y patólogos. Los pacientes fueron considerados para CRS e HIPEC si se determinaba que eran aptos para la cirugía y si las imágenes radiológicas sugerían que se podía lograr una citorreducción quirúrgica completa. Se analizó la morbilidad y mortalidad después de la cirugía. Se realizó un análisis de supervivencia tras la discusión en el MDT. RESULTADOS: En total, se discutieron 155 pacientes (tasa varón/mujer 0,96) con una edad media de 57 ± 17 años. Hasta el momento, 22 (14,2%) habían sido sometidos a CRS y HIPEC y la mediana de PCI en el grupo quirúrgico fue de 17,0. La citorreducción completa se logró en 19 (86,4%), las complicaciones de Clavien-Dindo grado I/II ocurrieron en 16/22, sin morbilidad de grado III/IV, ni mortalidad a los 30 días. La mediana de seguimiento fue de 15,0 meses y la supervivencia a los 2 años desde el momento de la revisión en el National PM MDT fue del 66,7%. CONCLUSIÓN: El National PM MDT centralizado fue eficaz en la selección de pacientes adecuados para CRS e HIPEC, presentando un buen resultado a partir de dicha selección.

A Radon Background-subtraction Algorithm for Electronic Personal Dosimeters.

Many first responders are outfitted with electronic personal dosimeters to recognize and be alerted to radiological hazards during their response operations. These dosimeters provide invaluable measurement data for force protection, allowing the first responder to assess a response situation and take protective measures for themselves and other individuals involved based on instrument readings of dose rate or cumulative dose. However, capabilities of common electronic personal dosimeters to identify and distinguish various contributions to the instrument reading, in particular from natural radiological sources, are rather limited. An algorithm has been developed for two-channel electronic personal dosimeters that quantifies the signal contribution from radon progeny and allows for background subtraction from radon and radon progeny in the instrument reading. This algorithm will be particularly useful in operational scenarios where first responders may be subject to rapidly changing levels of natural background radiation, which could mimic the presence of anthropogenic sources of ionizing radiation.

Optimization of Spectral String Data Analysis Using a Binomial Discriminator for Weak-source Detection Decisions.

Operational health physics applications, such as radiological and nuclear monitoring and detection for homeland security or radiation protection purposes, generate time sequences of independent individual measurement data. Statistical algorithms have been developed that use the analysis of patterns in the data strings to enhance the test statistic for the decision on the absence or presence of a radiation source. These hypothesis test procedures have been applied to spectral data and have been optimized for the highest rate of correct identification of a weak Cs source at constant false positive detection rates. Optimization of correct detection decisions was investigated for various string data sequence lengths and for the regions of interest in the gamma spectrum. The highest correct source identification is achieved for string data analyses of the spectral contributions that maximize a [INCREMENT]µ/σ criterion, including energy regions around and containing the photopeak, but potentially also regions in the gamma spectrum other than those photopeak energies.

Low-Fidelity Spectral Analysis Utilizing a Binomial Discriminator for Weak-Source Detection Decisions.

The identification of radiological sources by analysis of a gamma spectrum usually relies on the location of the set of radionuclide-specific electron energies corresponding to the incident photons interacting by photoelectric absorption in the detection medium. The challenge in low-level detection applications is the identification of these "photopeaks" above the background counts registered in the detector from the natural radiation environment and system noise. For source detection decisions, regions of the gamma spectrum other than at the photopeak energies may provide additional information about the presence of a source and allow for a higher rate of correct identification of a weak source. A statistical algorithm utilizing low-fidelity spectral data partitioned into three distinct regions and employing a binomial discriminator was tested in a laboratory setting against the traditional approach of source identification by exceeding a decision threshold within the photopeak region of interest. For an unshielded Cs source with no significant scatter between the source and the detector, the traditional peak identification method performs as well or better than most algorithm settings for various source strengths. However, an algorithm which also includes information in the energy range of Compton scattered photons provides improved detection capabilities for shielded weak sources. Such algorithms, including higher-fidelity developments, could be deployed to improve current tools for the search for orphan radiological sources and in the characterization of low-level environmental contamination.

Gamma and Beta Absorbed Dose Conversion Coefficients in the Range from 10 keV to 10 MeV for Accidental Exposures From Point Sources Placed in Clothing in Proximity to the Body.

Retrospective dose assessment following acute radiation exposures during radiological incidents can be difficult and inaccurate due to the large uncertainties associated with dose estimation. However, rapid and accurate dose assessment is critical following an incident so that appropriate treatment can be provided to the patient as early as possible. Incident dose assessment relies heavily on biological dosimetry with corresponding large uncertainties for inhomogeneous exposures, resulting from the estimates of whole-body doses, while the assessment of absorbed doses to individual tissues might actually be more appropriate for acute radiation exposures. Incident exposure scenarios for orphan sources placed in a breast or back pants pocket were modeled using the International Commission on Radiological Protection computational reference male and female and the Monte Carlo N-particle code MCNP6 to compute absorbed dose conversion coefficients for organs of interest for monoenergetic photon and beta sources. The absorbed dose conversion coefficients are intended for use in conjunction with source information to rapidly estimate absorbed doses to organs of interest from radiological sources in one of the two pocket geometries. Absorbed dose conversion coefficients also have been calculated specifically for Co, Cs, and Ir. Those absorbed dose conversion coefficients were applied to data from a radiological incident in Yanango, Peru, for comparison with published dose assessments; the results agree within 20%. The conversion coefficients are expected to provide an accurate tool for assessing doses for the modeled geometries, provided uncertainties due to the exact source-body geometry and exposure time are considered.

[Tips and technical issues for performing transoral endoscopic thyroidectomy with vestibular approach (TOETVA): a novel scarless technique for neck surgery]. / Tipps und technische Aspekte zur Durchführung der transoralen endoskopischen Thyreoidektomie mit vestibulärem Zugang (TOETVA): eine neue narbenlose Technik für die Halschirurgie.

BACKGROUND: Nowadays, minimally invasive thyroid and parathyroid gland resections for both benign and malignant tumors are rarely performed. Recently, promising new endoscopic transoral approaches to the anterior neck have been described with good results and few complications. This study describes the first clinical series in Germany using transoral endoscopic thyroidectomy-vestibular approach (TOETVA) and identifies technical issues and solutions. METHODS: The technique is indicated for hemithyroidectomy in patients without pre-existing neck operations. The technical steps consist of a 10 mm incision at the center of the oral vestibule, followed by subplatysmal hydrodissection. A blunt dissector stick is inserted creating a space below the platysma to the anterior neck and the infrahyoid muscles then three trocars are inserted in the vestibular area. After separation of the infrahyoid muscles, the thyroid isthmus is transected. Anatomical structures, such as the superior thyroid artery, parathyroid glands and the recurrent laryngeal nerve can be easily identified with magnification. Intraoperative neuromonitoring is used routinely, adding safety in avoiding nerve damage. RESULTS: An optimal operative field due to subplatysmal dissection enables exposure of the thyroid and parathyroid glands. Several critical steps and suitable solutions were identified in the study. 1 Positioning of the team and technical improvements using the a 4K laparoscopic tower allowing enhanced view of the anatomy especially for dissection of the recurrent laryngeal nerve. 2. Lateral and upper positioning of lateral trocars avoiding mental nerve injury. 3. Initial hydrodissection of the subplatysmal space. 4. Use of one dissector progressively creating the operative space in the anterior cervical region. 5. Using internal-external sutures to retract the infrahyoid muscles. 6. Intraoperative neuromonitoring used routinely through the trocars or percutaneously through a 1 mm incision. 7. Extraction of the specimen through a recovery bag. 8. Drainages are possible, but can be avoided in small operative fields. CONCLUSION: The new TOETVA technique for thyroid surgery is a promising option for selected patients to enable transoral thyroid and parathyroid surgery through the vestibular approach. Further studies in clinical series, especially regarding safety are needed to evaluate the indications of the technique.

[Surgical treatment of peritoneal metastases of gastric cancer]. / Chirurgische Therapie beim peritoneal metastasierten Magenkarzinom.

BACKGROUND: Up to 17% of all patients with gastric cancer are diagnosed with the presence of peritoneal metastases, which is associated with a poor prognosis. The most promising results were shown with multimodal treatment regimens including systemic chemotherapy and cytoreductive surgery (CRS). A subsequent hyperthermic intraperitoneal chemotherapy (HIPEC).possibly has a positive effect and is currently being tested. OBJECTIVES: This manuscript highlights the key role of CRS and HIPEC in patients with peritoneal metastases of gastric cancer and illustrates which patients benefit from this intensive therapy. METHODS: We performed a comprehensive review of the literature to demonstrate relevant aspects in the treatment of peritoneal metastases in gastric cancer. RESULTS: The use of CRS and HIPEC improves the overall survival to 11 months compared to best supportive care in selected patients. Patients who present with low volume peritoneal disease (peritoneal cancer index ≤6) have the best prognosis. This intensive treatment is associated with a relatively high morbidity (15-50%) and mortality (1-10%). Complete cytoreduction, i.e. a complete macroscopic absence of tumor tissue after resection is the most important prognostic factor. CONCLUSION: The CRS and HIPEC procedures have a proven survival benefit in selected patients. Due to the relatively high morbidity and mortality, the evaluation should be performed by an experienced team including a surgical oncologist, medical oncologist and intensive care physician, to achieve the highest rate of complete cytoreduction in combination with low morbidity; however, the effect of HIPEC has to be proven and the results of the randomized GASTRIPEC trial are awaited.

Enhancing Test Statistics by Utilizing Data Patterns in Sequential Measurement Strings in Radiation Detection.

Operational health physics applications, such as radiological and nuclear monitoring and detection for homeland security or radiation protection purposes, generate time sequences of independent individual measurement data. Statistical algorithms have been developed that utilize the analysis of patterns in data strings to enhance the test statistic for the decision on the absence or presence of a radiological source. Theoretical expectations have been verified in laboratory measurements for various lengths of data strings. Null hypothesis test performance and source detection efficacy have been shown to improve compared to the traditional method of achieving a detection decision by the comparison of a measured value to a fixed decision threshold.

JAM-A as a prognostic factor and new therapeutic target in multiple myeloma.

Cell adhesion in the multiple myeloma (MM) microenvironment has been recognized as a major mechanism of MM cell survival and the development of drug resistance. Here we addressed the hypothesis that the protein junctional adhesion molecule-A (JAM-A) may represent a novel target and a clinical biomarker in MM. We evaluated JAM-A expression in MM cell lines and in 147 MM patient bone marrow aspirates and biopsies at different disease stages. Elevated JAM-A levels in patient-derived plasma cells were correlated with poor prognosis. Moreover, circulating soluble JAM-A (sJAM-A) levels were significantly increased in MM patients as compared with controls. Notably, in vitro JAM-A inhibition impaired MM migration, colony formation, chemotaxis, proliferation and viability. In vivo treatment with an anti-JAM-A monoclonal antibody (αJAM-A moAb) impaired tumor progression in a murine xenograft MM model. These results demonstrate that therapeutic targeting of JAM-A has the potential to prevent MM progression, and lead us to propose JAM-A as a biomarker in MM, and sJAM-A as a serum-based marker for clinical stratification.

Pan-Raf co-operates with PI3K-dependent signalling and critically contributes to myeloma cell survival independently of mutated RAS.

Direct therapeutic targeting of oncogenic RAS is currently still impossible due to lack of suitable pharmacological inhibitors. Because specific blockade of druggable RAS effectors might represent an alternative treatment approach, we evaluated the role of the Raf complex for multiple myeloma (MM) pathobiology. We found frequent overexpression of the Raf isoforms (A-, B- and C-Raf) and downstream activation of MEK1,2/ERK1,2 in MM cells. Concomitant inhibition of all Raf isoforms (pan-Raf inhibition) by RNAi or pharmacological inhibitors was required to strongly induce apoptosis in human MM cell lines (HMCLs), in primary MM cells in vitro, and in a syngeneic MM mouse model in vivo. The anti-MM effect of pan-Raf inhibition did not correlate with the RAS mutation status, and functionally appeared to involve both MEK-dependent and -independent mechanisms. Furthermore, transcriptome analyses revealed that pan-Raf activity affects PI3K-dependent signalling, thus highlighting a functional link between the RAS/Raf and PI3K/mTOR/Akt pro-survival pathways. Accordingly, pharmacological inhibition of PI3K strongly enhanced the anti-MM effect of pan-Raf inhibition in MM cell lines and in primary MM cells in vitro and in vivo. Concomitant pan-Raf/PI3K inhibition was also effective in carfilzomib- and lenalidomide-resistant MM models underscoring that this attractive therapeutic anti-MM strategy is suitable for immediate clinical translation.

Towards the rational design of novel drugs based on solubility, partitioning/distribution, biomimetic permeability and biological activity exemplified by 1,2,4-thiadiazole derivatives.

Novel 1,2,4-thiadiazole derivatives as potent neuroprotectors were synthesized and identified. Their ability to inhibit the glutamate stimulated Ca2+ uptake was investigated. The solubility of thiadiazoles was measured in a buffer solution (pH 7.4) at 298 K. The distribution coefficients in 1-octanol/buffer (pH 7.4) and 1-hexane/buffer (pH 7.4) immiscible phases as model systems imitating the gastrointestinal tract epithelium and the blood-brain barrier were determined. Permeation experiments the new Permeapad™ barrier using Franz diffusion cells were conducted and the apparent permeability coefficients were obtained. The influence of the compound structure on the physicochemical properties determining the bioavailability of drug-like substances was revealed. Solubility-permeability interplay has been assessed to evaluate potential bioavailability of the compounds studied.

Transanal drainage tube reduces rate and severity of anastomotic leakage in patients with colorectal anastomosis: A case controlled study.

BACKGROUND AND AIMS: The aim of this study was to investigate the clinical usefulness of the placement of a transanal drainage tube to prevent anastomotic leakage in colorectal anastomoses. MATERIAL AND METHODS: This single-center retrospective trial included all patients treated with surgery for benign or malign colorectal disease between January 2009 and December 2012. The transanal drainage tube was immediately placed after colorectal anastomosis until day five and was routinely used since 2010. Patients treated with a transanal drainage tube were compared with the control group. Statistical analysis was performed using Fisher's exact or Chi-square tests for group comparison and a linear regression model for multivariate analysis. RESULTS: This study included 242 patients (46% female; median age 63 years; range 18-93); 34% of the patients underwent a laparoscopic procedure, and 57% of the patients received a placement of a transanal drainage tube. Anastomotic leakage occurred in 19 patients (7.9%). Univariate analysis showed a higher rate of anastomotic leakage in patients with an ASA score 4 (p = 0.02) and a lower rate in patients with transanal drainage placement (3.6% vs. 13.6%; p = 0.007). The grading of the complication of anastomotic leakage was reduced with transanal drainage (e.g., Dindo â‰§ 3b: 20.0% vs. 92.9%; p = 0.006), and the hospital stay was shortened (17.6 ± 12.5 vs. 22.1 ± 17.6 days; p = 0.02). Multivariate analysis revealed that transanal drainage was the only significant factor (HR = -2.90; -0.168 to -0.032; p = 0.007) affecting anastomotic leakage. CONCLUSIONS: Placement of a transanal drainage tube in patients with colorectal anastomoses is a safe and simple technique to perform and reduces anastomotic leakage, the severity of the complication and hospital stay.

Chitosan based micro- and nanoparticles for colon-targeted delivery of vancomycin prepared by alternative processing methods.

The aim of this work was to prepare chitosan (CH) based particulate formulations for colon delivery of vancomycin (VM). Chitosan microparticles (MPs) and nanoparticles (NPs) loaded with VM were prepared using different CH/tripolyphosphate (TPP) molar ratios and different technological processes. In particular, nanoparticles were prepared by ionic gelation and freeze-drying to recover these particles, or, alternatively, by spray-drying method. Microparticles were prepared using a different spray-dryer. Micro- and nanoparticles were characterized in terms of size distributions by photon correlation spectroscopy (PCS), while encapsulation and drug loading efficiencies were studied using a dialysis method. Fourier Transform Infrared Spectroscopy (FT-IR) was employed to determine the surface composition of the micro- and nanoparticles respectively, and the morphologies of the developed systems were studied by scanning electron microscopy (SEM). Water uptake as well as drug release profiles were also measured. Antibacterial activity against Staphylococcus aureus, a Gram-positive model strain, was evaluated. FT-IR results suggested an electrostatic interaction between VM and CH/TPP particles. Moreover, the particles were found to hold a positive zeta-potential, indicating the presence of CH on the particle surfaces. Particle size and encapsulation efficiency were mainly influenced by the different manufacturing processes employed. Nanoparticles obtained by spray-drying showed the best results in terms of water uptake and drug release rate. Moreover, they showed a good bactericidal activity against S. aureus.

Dynamic hydrostatic pressure enhances differentially the chondrogenesis of meniscal cells from the inner and outer zone.

This study analyses the influence of dynamic hydrostatic pressure on chondrogenesis of human meniscus-derived fibrochondrocytes and explores the differences in chondrogenic differentiation under loading conditions between cells derived from the avascular inner zone and vascularized outer region of the meniscus. Aggregates of human fibrochondrocytes with cell origin from the inner region or with cell origin from the outer region were generated. From the two groups of either cell origin, aggregates were treated with dynamic hydrostatic pressure (1Hz for 4h; 0.55-5.03MPa, cyclic sinusoidal) from day 1 to day 7. The other aggregates served as unloaded controls. At day 0, 7, 14 and 21 aggregates were harvested for evaluation including histology, immunostaining and ELISA analysis for glycosaminoglycan (GAG) and collagen II. Loaded aggregates were found to be macroscopically larger and revealed immunohistochemically enhanced chondrogenesis compared to the corresponding controls. Loaded or non-loaded meniscal cells from the outer zone showed a higher potential and earlier onset of chondrogenesis compared to the cells from the inner part of the meniscus. This study suggests that intrinsic factors like cell properties in the different areas of the meniscus and their reaction on mechanical load might play important roles in designing Tissue Engineering strategies for meniscal repair in vivo.

Incisional hernia rate after open abdomen treatment with negative pressure and delayed primary fascia closure.

PURPOSE: Various techniques for delayed primary fascia closure have been published in patients treated with open abdomen (OA) and application of negative pressure, but to date, no data are available on incisional hernia (IH) rate. The aim of this retrospective analysis was to investigate the long-term outcome of this patient population with special interest in IH development. METHODS: Two hundred and nine consecutive patients, 90(43 %) female, were treated at our institution for various abdominal emergencies involving OA from June 2006 to June 2011. Mean age was 63(16-92) years. The indication was abdominal sepsis in 155(74 %) patients, ischemia in 24(12 %) and other reasons in 30(14 %). Hospital mortality was 21 %(n = 44); and planned ventral hernia was 7 %(n = 15); and mortality until follow-up was 16 %(n = 25), and 9 %(n = 13) patients were lost to follow-up, leaving 112 patients for evaluation of IH development. RESULTS: The rate of IH for patients with OA and delayed primary fascia closure was overall 35 % at a median (range) follow-up time of 26(12-81) months. Mean time for development of a ventral hernia was 11 months; 21(57 %) patients underwent surgery for symptomatic hernia (2 emergency operations for incarceration). Kaplan-Meier estimate for 5 years gave a 66 % IH rate. BMI, small bowel as source of infection and rapid adsorbable interrupted suture were identified risk factors. CONCLUSION: The rate of IH after open abdomen treatment with delayed primary fascia closure is high with a running suture with slow absorbable suture material showing the best results.