Ilaria Benzoni

This study addresses a joint nuclear magnetic resonance (NMR) and electron paramagnetic resonance (EPR) spectroscopy approach to provide a platform for dynamic assessment of kidney viability and metabolism. On porcine kidney models, ROS production, oxidative damage kinetics, and metabolic changes occurring both during the period between organ retrieval and implantation and after kidney graft were examined. The ¹H-NMR metabolic profile—valine, alanine, acetate, trimetylamine-N-oxide, glutathione, lactate, and the EPR oxidative stress—resulting from ischemia/reperfusion injury after preservation (8 h) by static cold storage (SCS) and ex vivo machine perfusion (HMP) methods were monitored. The functional recovery after transplantation (14 days) was evaluated by serum creatinine (SCr), oxidative stress (ROS), and damage (thiobarbituric-acid-reactive substances and protein carbonyl enzymatic) assessments. At 8 h of preservation storage, a significantly (p < 0.0001) higher ROS production was measured in the SCS vs. HMP group. Significantly higher concentration data (p < 0.05–0.0001) in HMP vs. SCS for all the monitored metabolites were found as well. The HMP group showed a better function recovery. The comparison of the areas under the SCr curves (AUC) returned a significantly smaller (−12.5 %) AUC in the HMP vs. SCS. EPR-ROS concentration (μmol·g⁻¹) from bioptic kidney tissue samples were significantly lower in HMP vs. SCS. The same result was found for the NMR monitored metabolites: lactate: −59.76%, alanine: −43.17%; valine: −58.56%; and TMAO: −77.96%. No changes were observed in either group under light microscopy. In conclusion, a better and more rapid normalization of oxidative stress and functional recovery after transplantation were observed by HMP utilization.

Background: The management of rectal cancer is multimodal and involves a multidisciplinary team of cancer specialists with expertise in medical oncology, surgical oncology, radiation oncology and radiology. It is crucial for highly specialized centers to collaborate via networks that aim to maintain uniformity in every aspect of treatment and rigorously gather patients’ data, from the first clinical evaluation to the last follow-up visit. The Advanced International Mini-Invasive Surgery (AIMS) academy clinical research network aims to create a rectal cancer registry. This will prospectively collect the data of patients operated on for non-metastatic rectal cancer in high volume colorectal surgical units through a well design pre-fashioned database for non-metastatic rectal cancer, in order to take all multidisciplinary aspects into consideration. Methods/Design: The protocol describes a multicenter prospective observational cohort study, investigating demographics, frailty, cancer-related features, surgical and radiological parameters, and oncological outcomes among patients with non-metastatic rectal cancer who are candidates for surgery with curative intent. Patients enrolled in the present registry will be followed up for 5 years after surgery. Discussion: Standardization and centralization of data collection for neoplastic diseases is a virtuous process for patient care. The creation of a register will allow the control of the quality of treatments provided and permit prospective and retrospective studies to be carried out on complete and reliable high quality data. Establishing data collection in a prospective and systematic fashion is the only possibility to preserve the enormous resource that each patient represents.

Thermosensitive chitosan/glycerophosphate (C/GP) solutions exhibiting sol-gel transition around body temperature were prepared to develop a class of injectable hydrogel platforms for the imaging and loco-regional treatment of hepatocellular carcinoma (HCC). Indocyanine green (ICG) was loaded in the thermosensitive solutions in order to assess their potential for the detection of tumor nodules by fluorescence. The gel formation of these formulations as well as their gelling time, injectability, compactness and resistance of gel structure, gelling temperature, storage conditions, biodegradability, and in vitro dye release behavior were investigated. Ex vivo studies were carried out for preliminary evaluation using an isolated bovine liver. Gel strengths and gelation rates increased with the cross-link density between C and GP. These behaviors are more evident for C/GP solutions, which displayed a gel-like precipitation at 4°C. Furthermore, formulations with the lowest cross-link density between C and GP exhibited the best injectability due to a lower resistance to flow. The loading of the dye did not influence the gelation rate. ICG was not released from the hydrogels because of a strong electrostatic interaction between C and ICG. Ex vivo preliminary studies revealed that these injectable formulations remain in correspondence of the injected site. The developed ICG-loaded hydrogels have the potential for intraoperative fluorescence imaging and local therapy of HCC as embolic agents. They form in situ compact gels and have a good potential for filling vessels and/or body cavities.

Kidney transplantation is the only potentially curative treatment for patient facing end-stage renal disease, and it is now routinely used. Its use is mainly limited by the supply of transplantable donor organs, which far exceeds the demand. Regenerative medicine and tissue engineering offer promising means for overcoming this shortage. In the present study, we developed and validated a protocol for producing acellular rat renal scaffolds. Left kidneys were removed from 26 male Lewis rats (weights: 250–350 g) and decellularized by means of aortic anterograde perfusion with ionic and anionic detergents (Triton X-100 1% and SDS 1%, respectively). 19 scaffolds thus obtained (and contralateral native kidneys as controls) were deeply characterized in order to evaluate the decellularization quality, the preservation of extracellular matrix components and resultant micro-angioarchitecture structure. The other 7 were transplanted into 7 recipient rats that had undergone unilateral nephrectomy. Recipients were sacrificed on post-transplantation day 7 and the scaffolds subjected to histologic studies. The dual-detergent protocol showed, with only 5 h of perfusion per organ, to obtain thoroughly decellularized renal scaffolds consisting almost exclusively of extracellular matrix. Finally the macro- and the microarchitecture of the renal parenchyma were well preserved, and the grafts were implanted with ease. Seven days after transplant, the scaffolds were morphologically intact although all vascular structures were obstructed with thrombi. Production and implantation of acellular rat renal scaffolds is a suitable platform for further studies on regenerative medicine and tissue engineering.