Tumor cell–derived extracellular vesicles (EVs) are being explored as circulating biomarkers, but it is unclear whether bulk measurements will allow early cancer detection. We hypothesized that a single-EV analysis (sEVA) technique could potentially improve diagnostic accuracy. Using pancreatic cancer (PDAC), we analyzed the composition of putative cancer markers in 11 model lines. In parental PDAC cells positive for KRAS ^mut and/or P53 ^mut proteins, only ~40% of EVs were also positive. In a blinded study involving 16 patients with surgically proven stage 1 PDAC, KRAS ^mut and P53 ^mut protein was detectable at much lower levels, generally in <0.1% of vesicles. These vesicles were detectable by the new sEVA approach in 15 of the 16 patients. Using a modeling approach, we estimate that the current PDAC detection limit is at ~0.1-cm ³ tumor volume, below clinical imaging capabilities. These findings establish the potential for sEVA for early cancer detection.

PURPOSE: Ostomy creation is often an integral part of the surgical management of various diseases including colorectal malignancies and inflammatory bowel disease. Stoma and peristomal complications may occur in up to 70% of patients following ostomy surgery. The aim of this scoping literature review was to synthesize evidence on the risk factors for developing complications following creation of a fecal ostomy. DESIGN: Scoping literature review. SEARCH STRATEGY: Two independent researchers completed a search of the online bibliographic databases PubMed, MEDLINE, Cochrane, Google Scholar, and EMBASE for all articles published between January 1980 and December 2018. The search comprised multiple elements including systematic literature reviews with meta-analysis of pooled findings, randomized controlled trials, cohort studies, observational studies, other types of review articles, and multiple case reports. We screened 307 unique titles and abstracts; 68 articles met our eligibility criteria for inclusion. The methodological rigor of study quality included in our scoping review was variable. FINDINGS/CONCLUSIONS: We identified 6 risk factors associated with an increased likelihood of stoma or peristomal complications (1) age more than 65 years; (2) female sex; (3) body mass index more than 25; (4) diabetes mellitus as a comorbid condition; (5) abdominal malignancy as the underlying reason for ostomy surgery; and (6) lack of preoperative stoma site marking and WOC/ostomy nurse specialist care prior to stoma surgery. We also found evidence that persons with a colostomy are at a higher risk for prolapse and parastomal hernia. IMPLICATIONS: Health care professionals should consider these risk factors when caring for patients undergoing fecal ostomy surgery and manage modifiable factors whenever possible. For example, preoperative stoma site marking by an ostomy nurse or surgeon familiar with this task, along with careful perioperative ostomy care and education of the patient by an ostomy nurse specialist, are essential to reduce the risk of modifiable risk factors related to creation of a fecal ostomy.

Radiation-induced rectovaginal fistula (RI-RVF) is a chronic and serious condition with a significant influence on quality of life. The aim of this study is to evaluate the results of surgical treatment of rectovaginal fistulas of patients previously undergoing radiotherapy.

Being one of the most common dermatological inflammatory disorders, psoriasis is a frequent subject of research. It is considered to be a T cell-dependent immune disease whose pathogenesis is influenced by cytokines, such as IL-10, IL-17A, IL-17RA, IL-23A and IL-23R. The present study examines whether the expression of selected genes is correlated with the clinical course of psoriasis, assessed by the PASI, BSA and DLQI scales. Skin biopsies and blood from 60 patients with psoriasis and 24 healthy controls were obtained for RNA isolation. These were subjected to RT-PCR for IL-10, IL-17A, IL-17RA, IL-23A and IL-23R genes. The results were presented as an RQ value. IL-17A and IL-23R expression levels were higher in psoriatic skin compared to controls, while IL-10 expression was lower. A positive correlation was also found between RQ for IL-23A and PASI index. Psoriatic skin is characterised by elevated expression of IL-17A and IL-23R and decreased expression of IL-10. This indicates that the selected cytokines may be one of the factors involved in the pathogenesis and pathomechanism of psoriasis, but more studies need to be made before we can elucidate the exact reason for the unbalance in cytokine expression levels.

Background: Tissue-engineered blood vessels (TEBV) represent an attractive approach for overcoming reconstructive problems associated with vascular diseases in humankind by providing small caliber vascular grafts. The study evaluates biocompatibility and bioaffinity of vascular prostheses made from chitosan-modified bacterial cellulose (MBC) as potential scaffolds for TEBV. Methods: During the study, acute oral toxicity, up-and-down procedure (UDP), OECD test No. 425 on 10 Imp:WIST rats, intradermal reactivity on three Imp:BN albino rabbits, and sensitization on 15 Imp:DH guinea pigs were performed. The local effects were determined 1 month after intramuscular implantation of prostheses in 30 Imp:WIST rats. Histopathological and pathomorphological studies were conducted following complete removal of implants with peri-implant tissue. Results: There were no signs of toxicity; the median lethal oral dose (LD50) was greater than 2 g/kg body weight for the rats. No allergic reactions were observed in the case of the guinea pig maximization test. Vascular grafts did not induce significant reactive changes in intradermal reactivity test (Main Irritation Index value 0.03) and do not induce inflammatory changes or hyperplasia of the muscle tissue surrounding the implant. Histopathological examination revealed ingrown vascular-connective bands. Conclusions: Tubes made of MBC offer strong potential for use in future TEBV programs for vascular surgery. Lay Summary: Currently, the number of autologous grafts for coronary artery disease and for peripheral artery disease is limited. Particularly materials that will have contact with blood must comply with certain requirements such as mechanical strength, biocompatibility, and no potential to evoke adverse reactions. Bacterial nanocellulose modified with chitosan (MBC) due to its mechanical and biological properties is a promising material for replacing small-diameter vessels grafts. Although previous studies have not shown the toxicity of nanocellulose, we want to check whether medical products based on MBC will be safe when testing in vivo. Thirty Imp:WIST rats and 15 Imp:DH guinea pigs were subject of thorough analysis of potential toxicological and sensitization effect that may develop after applying vascular prostheses made from MBC to living organism. The analysis involved also histopathological and pathomorphological studies following complete removal of implants with peri-implant tissue. The results show that MBC prostheses do not cause any allergic, intradermal reactions and finally, do not display acute toxicity towards the organism in which it is implanted. Moreover, they had not induced inflammatory changes or hyperplasia of the muscle tissue surrounding the implantation sites, thus showing good biocompatibility. Obtained results were discussed with other available studies investigating various aspects of bacterial cellulose or modified bacterial cellulose influence on cells and tissues in both in vitro and in vivo studies. This is the first study analyzing the toxicological and sensitization effect which MBC may evoke and confirm the strong potential for use in future TEBV programs for vascular surgery. Graphical