Role of perfusion CT in the evaluation of metastatic nodal tumor response after radiochemotherapy in head and neck cancer: preliminary findings

OBJECTIVE: To assess changes of CT perfusion parameters (ΔPCTp) of cervical lymph node metastases from head and neck cancer (HNC) before and after radiochemotherapy (RT-CT) and their association with nodal tumor persistence. PATIENTS AND METHODS: Eligibility criteria included HNC (Stage III-IV) candidates for RT-CT. Patients underwent perfusion CT (PCT) at baseline 3 weeks and 3 months after RT-CT. Blood volume (BV), blood flow (BF), mean transit time (MTT) and permeability surface (PS) were calculated. PET/CT examination was also performed at baseline and 3 months after treatment for metabolic assessment. RESULTS: Between July 2012 and May 2016, 27 patients were evaluated. Overall, only 3 patients (11%) experienced tumor persistence in the largest metastatic lymph node. A significant reduction of all PCTp values (p<0.0001), except MTT (from 6.3 to 5.7 s; p=0.089), was observed at 3 weeks post-RT-CT compared to baseline. All PCTp values including MTT were significantly lower at 3-month follow-up compared to baseline (p<0.05). Moreover, a statistical significant association was observed between nodal tumor persistence and high BF values (p=0.045) at 3 months after treatment that did not occur for the other parameters. CONCLUSIONS: Our preliminary findings show that all PCTp except MTT are significantly reduced after RT-CT. High BF values at 3 months post-RTCT are predictive of nodal tumor persistence

Multimodal approach of advanced gastric cancer: Based therapeutic algorithm

Gastric cancer (GC) is the third leading cause of cancer death in both sexes worldwide, with the highest estimated mortality rates in Eastern Asia and the lowest in Northern America. However, the availability of modern treatment has improved the survival and the prognosis is often poor due to biological characteristics of the disease. In oncology, we are living in the "Era" of target treatment and, to know biological aspects, prognostic factors and predictive response informations to therapy in GC is mandatory to apply the best strategy of treatment. The purpose of this review, according to the recently published English literature, is to summarize existing data on prognostic aspects and predictive factors to response to therapy in GC and to analyze also others therapeutic approaches (surgery and radiotherapy) in locally, locally advanced and advanced GC. Moreover, the multidisciplinary approach (chemotherapy, surgery and radiotherapy) can improve the prognosis of GC

Use of complementary and alternative medicine (CAM) in cancer patients. An italian multicenter survey

INTRODUCTION: Complementary and Alternative Medicine (CAM) include a wide range of products (herbs, vitamins, minerals, and probiotics) and medical practices, developed outside of the mainstream Western medicine. Patients with cancer are more likely to resort to CAM first or then in their disease history; the potential side effects as well as the costs of such practices are largely underestimated. PATIENTS AND METHOD: We conducted a descriptive survey in five Italian hospitals involving 468 patients with different malignancies. The survey consisted of a forty-two question questionnaire, patients were eligible if they were Italian-speaking and receiving an anticancer treatment at the time of the survey or had received an anticancer treatment no more than three years before participating in the survey. RESULTS: Of our patients, 48.9% said they use or have recently used CAM. The univariate analysis showed that female gender, high education, receiving treatment in a highly specialized institute and receiving chemotherapy are associated with CAM use; at the multivariate analysis high education (Odds Ratio, (OR): 1.96 95% Confidence Interval, CI, 1.27-3.05) and receiving treatment in a specialized cancer center (OR: 2.75 95% CI, 1.53-4.94) were confirmed as risk factors for CAM use. CONCLUSION: Roughly half of our patients receiving treatment for cancer use CAM. It is necessary that health professional explore the use of CAM with their cancer patients, educate them about potentially beneficial therapies in light of the limited available evidence of effectiveness, and work towards an integrated model of health-care provision

Electrospun PHEA-PLA/PCL Scaffold for Vascular Regeneration: A Preliminary in\ua0Vivo Evaluation

Background. There is increasing interest in the development of vessel substitutes, and many studies are currently focusing on the development of biodegradable scaffolds capable of fostering vascular regeneration. We tested a new biocompatible and biodegradable material with mechanical properties similar to those of blood vessels. Methods. The material used comprises a mixture of a,b-poly(N-2-hydroxyethyl)-D,L-aspartamide (PHEA) and polylactic acid (PLA), combined with polycaprolactone (PCL) by means of electrospinning technique. Low-molecular-weight heparin was also linked to the copolymer. A tubular PHEA-PLA/PCL sample was used to create an arteriovenous fistula in a pig model with the use of the external iliac vessels. The flow was assessed by means of Doppler ultrasound examination weekly, and 1 month after the implantation we removed the scaffold for histopathologic evaluation. Results. The implants showed a perfect leak-proof seal and adequate elastic tension to blood pressure. About w3 weeks after the implantation, Doppler examination revealed thrombosis of the graft, so we proceeded to its removal. Histologic examination showed chronic inflammation, with the presence of foreign body cells and marked neovascularization. The material had been largely absorbed, leaving some isolated spot residues. Conclusions. The biocompatibility of PHEA-PLA/PCL and its physical properties make it suitable for the replacement of vessels. In the future, the possibility of functionalizing the material with a variety of molecules, to modulate the inflammatory and coagulative responses, will allow obtaining devices suitable for the replacement of native vessels

Electrospun Polyhydroxyethyl-Aspartamide-Polylactic Acid Scaffold for Biliary Duct Repair: A Preliminary In\ua0Vivo Evaluation

Tissue engineering has emerged as a new approach with the potential to overcome the limitations of traditional therapies. The objective of this study was to test whether our polymeric scaffold is able to resist the corrosive action of bile and to support a cell's infiltration and neoangiogenesis with the aim of using it as a biodegradable tissue substitute for serious bile duct injuries. In particular, a resorbable electrospun polyhydroxyethyl-aspartamide-polylactic acid (90 mol% PHEA, 10 mol% PLA)/polycaprolactone (50:50 w/w) plate scaffold was implanted into rabbit gallbladder to assess the in\ua0vivo effects of the lytic action of the bile on the scaffold structure and then as a tubular scaffold to create a biliary-digestive anastomosis as well. For the above evaluation, 5 animals were used and killed after 15 days and 5 animals after 3 months. At 15-day and 3-month follow-ups, the fibrillar structure was not digested by lytic action bile. The fibers of the scaffold were organized despite being in contact with bile action. A new epithelial tissue appeared on the scaffold surface suggesting the suitability of this scaffold for future studies of the repair of biliary tract injuries with the use of resorbable copolymer on biliary injuries

The role of clinicopathologic and molecular prognostic factors in the post-mastectomy radiotherapy (PMRT): a retrospective analysis of 912 patients

OBJECTIVE: To assess the association of clinicopathologic and molecular features with loco-regional recurrence (LRR) in post-mastectomy breast cancer patients with or without adjuvant radiotherapy (PMRT). PATIENTS AND METHODS: We retrospectively reviewed data of patients undergone to mastectomy followed or not by PMRT between January 2004 and June 2013. The patients were divided according to clinicopathologic and molecular sub-classification features. LRR and Cancer Specific Survival (CSS) were calculated using the Kaplan-Meier method; the prognostic factors were compared using long-rank tests and Cox regression model. RESULTS: A total of 912 patients underwent to mastectomy of whom 269 (29.5%) followed by PMRT and 643 (70.5%) not; among the PMRT group, 77 underwent to the chest wall (CW) and 202 to the chest wall and lymphatic drainage (CWLD) irradiation. The median follow-up was 54 months (range, 3-118). No significant difference in terms of LRR and CSS was found between non-PMRT and PMRT group (p=0.175; and p=0.628). The multivariate analysis of LRR for patients who did not undergo PMRT showed a significant correlation with the presence of extracapsular extension (ECE) (p=0.049), Ki-67>30% (p=0.048) and triple negative status (p=0.001). In the PMRT group, triple negative status resulted as the only variable significantly correlated to LRR (p=0.006) at the multivariate analysis and T-stage also showed a trend to significance (p=0.073). Finally, no difference in LRR control was shown between CW and CWLD-PMRT (p=0.078). CONCLUSIONS: After mastectomy ECE, a cut off of Ki-67>30% and triple negative status werestrictly correlated with LRR regardless of clinicopathologic stage. PMRT has a positive impact in decreasing LRR in patients with this molecular profile. Besides, CW might represent a valid option for patients with one to three positive nodes

Topical application of a hyaluronic acid-based hydrogel integrated with secretome of human mesenchymal stromal cells for diabetic ulcer repair

This preclinical proof-of-concept study aimed to evaluate the effectiveness of secretome therapy in diabetic mice with pressure ulcers. We utilized a custom-made hyaluronic acid (HA)-based porous sponge, which was rehydrated either with normal culture medium or secretome derived from human mesenchymal stromal cells (MSCs) to achieve a hydrogel consistency. Following application onto skin ulcers, both the hydrogel-only and the hydrogel + secretome combination accelerated wound closure compared to the vehicle group. Notably, the presence of secretome significantly enhanced the healing effect of the hydrogel, as evidenced by a thicker epidermis and increased revascularization of the healed area compared to the vehicle group. Notably, molecular analysis of healed skin revealed significant downregulation of genes involved in delayed wound healing and abnormal inflammatory response in ulcers treated with the hydrogel + secretome combination, compared to those treated with the hydrogel only. Additionally, we found no significant differences in therapeutic outcomes when comparing the use of secretome from fetal dermal MSCs to that from umbilical cord MSCs. This observation is supported by the proteomic profile of the two secretomes, which suggests a shared molecular signature responsible of the observed therapeutic effects

Phase II evaluation of dasatinib in the treatment of recurrent or persistent epithelial ovarian or primary peritoneal carcinoma: a Gynecologic Oncology Group study.

OBJECTIVES: Preclinical data suggest an important role for the sarcoma proto-oncogene tyrosine kinase (SRC) in the oncogenesis of epithelial ovarian cancer (EOC) or primary peritoneal carcinoma (PPC). The Gynecologic Oncology Group (GOG) conducted a Phase II trial to evaluate the efficacy and safety of dasatinib, an oral SRC-family inhibitor in EOC/PPC, and explored biomarkers for possible association with clinical outcome. METHODS: Eligible women had measurable, recurrent or persistent EOC/PPC and had received one or two prior regimens which must have contained a platinum and a taxane. Patients were treated with 100mg orally daily of dasatinib continuously until progression of disease or adverse effects prevented further treatment. Primary endpoints were progression-free survival (PFS)≥6months and response rate. Serial plasma samples were assayed for multiple biomarkers. Circulating free DNA was quantified as were circulating tumor and endothelial cells. RESULTS: Thirty-five (35) patients were enrolled in a two-stage sequential design. Of the 34 eligible and evaluable patients, 20.6% (90% confidence interval: 10.1%, 35.2%) had a PFS≥6months; there were no objective responses. Grade 3-4 toxicities were gastrointestinal (mostly nausea and emesis; n=4), pulmonary (dyspnea and/or pleural effusion; n=4) and pain (n=5), and infrequent instances of anemia, malaise, insomnia, rash, and central nervous system hemorrhage. Lack of clinical activity limited any correlation of biomarkers with outcome. CONCLUSION: Dasatinib has minimal activity as a single-agent in patients with recurrent EOC/PPC

BIOCOMPATIBILITY AND BIODEGRADABILITY OF ELECTROSPUN PHEA-PLA SCAFFOLDS: OUR PRELIMINARY EXPERIENCE IN A MURINE ANIMAL MODEL

We obtained a nano-fibrillar scaffold starting from a polymeric solution which, through electrospinning, gave a biodegradable material with optimal mechanical features and the capacity to allow cell adhesion. In this paper we report the in-vivo application on a murine animal model of two electrospun biodegradable materials, specifically designed to create tubular structures. In one case PHEA-PLA was co-spun with silk fibroin (Fibro-PHEAPLA) by a parallel electrospinning process to obtain a scaffold with two different polymeric fibers. In the other case, PHEA-PLA was mixed with polycaprolactone (PCLPHEA-PLA) to obtain a hybrid fibers scaffold. The in-vitro assay showed fibroblast colonization in both materials. The scaffolds were implanted in the dorsal fascial pouch of rats to evaluate their in-vivo Biocompatibility and tissue integration. Histopathological findings showed that after implantation a neutrophilic reaction associated to colliquative necrosis was predominant, particularly for PCL-PHEA-PLA. Fibro-PCL-PHEA caused a non organized stromal reaction. Cell adhesion was confirmed at SEM scan. Both materials were totally absorbed after 40 days with an inflammatory reaction. This preliminary study showed that biocompatibility of the scaffolds needs further investigation. The capability of the materials to be functionalized could allow us to modulate the inflammatory host response