Does the Overall Survival of the Resectable Periampullary Carcinomas Correlate with High Expression of p53 and ki67?

Introduction: Periampullary carcinomas represent a group of tumors that develop in a complex area, implying different anatomical structures. The most common histological type of periampullary carcinomas is the adenocarcinoma. The pancreatic type of periampullary adenocarcinomas has the worst prognosis. Immunohistochemical markers, such as ki-67 and p53, can be used in predicting survival. Material and method: we selected the patients with periampullary adenocarcinomas, intestinal or biliopancreatic type, with resectable tumors, and we performed immunohistochemical stains for ki-67 and p53 markers. The overall survival was analyzed according to the expression of immunohistochemical markers, TNM staging, tumor grade and perineural invasion. Results: Sixty-seven patients were included in the study. The median overall survival for the whole cohort was 12 months, with a 2-year survival rate of 25%. High rate of tumor proliferation (ki67 more than 80%) was significantly associated with shorter overall survival (median survival 3 months compared with 17 months for the group with ki67 index less than 80%). A high expression of p53 protein has been associated with low overall survival. The low survival was associated with poorly differentiated tumor grade and lymph node status. Conclusion: Both immunohistochemical expression of ki67 and p53 can be used as prognostic and predictive factors for overall survival of patients with resectable periampullary adenocarcinomas.

Accuracy of a no-biopsy approach for the diagnosis of coeliac disease across different adult cohorts.

OBJECTIVE: We aimed to determine the predictive capacity and diagnostic yield of a 10-fold increase in serum IgA antitissue transglutaminase (tTG) antibody levels for detecting small intestinal injury diagnostic of coeliac disease (CD) in adult patients. DESIGN: The study comprised three adult cohorts. Cohort 1: 740 patients assessed in the specialist CD clinic at a UK centre; cohort 2: 532 patients with low suspicion for CD referred for upper GI endoscopy at a UK centre; cohort 3: 145 patients with raised tTG titres from multiple international sites. Marsh 3 histology was used as a reference standard against which we determined the performance characteristics of an IgA tTG titre of ≥10×ULN for a diagnosis of CD. RESULTS: Cohort 1: the sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) for IgA tTG levels of ≥10×ULN at identifying individuals with Marsh 3 lesions were 54.0%, 90.0%, 98.7% and 12.5%, respectively. Cohort 2: the sensitivity, specificity, PPV and NPV for IgA tTG levels of ≥10×ULN at identifying individuals with Marsh 3 lesions were 50.0%, 100.0%, 100.0% and 98.3%, respectively. Cohort 3: the sensitivity, specificity, PPV and NPV for IgA tTG levels of ≥10×ULN at identifying individuals with Marsh 3 lesions were 30.0%, 83.0%, 95.2% and 9.5%, respectively. CONCLUSION: Our results show that IgA tTG titres of ≥10×ULN have a strong predictive value at identifying adults with intestinal changes diagnostic of CD. This study supports the use of a no-biopsy approach for the diagnosis of adult CD.

New Chimeric Groin Flap: Experimental Model in Rats.

AIM: Increased emphasis is on using tissue substitutes and stem cells to improve flap applicability and survival rates. To accomplish this, the first step is to have a versatile experimental flap, easy to harvest and use as a template. We sought to develop a reliable experimental chimeric groin flap with free mobility and reliable bloods supply that can be twisted, relocated, and integrated easily with other materials. MATERIALS AND METHODS: Ten male Wistar rats were included. The flap consists of a 2.5-cm skin paddle centered on the medial branch of the inferior epigastric artery and a 4.5/2-cm fat pad supplied by the lateral branch of the inferior epigastric artery. After being raised, flaps were resutured in their anatomical position. Flaps were followed up for 15 days. At the end of the study, the viability of flaps was analyzed by ultrahigh-frequency ultrasound, nontargeted contrast study, and histology assessment. RESULTS: All flaps survived without significant complications. Nontargeted microbubbles spread evenly in both the superficial and deep flap. Ultrasound assessment at day 15 showed no significant areas of necrosis or edema. Histology examination of 3 random flaps confirmed vessel patency and flap viability. CONCLUSION: We propose a simple, easy to harvest and reliable experimental flap which offers a main advantage of all-around mobility through its chimeric design. It is a suitable model for bioengineering studies as it can be used as a template for integration of tissue substitutes or stem cells, between its 2 components.

Role of Ultrahigh Frequency Ultrasound in Evaluating Experimental Flaps.

BACKGROUND: Experimental flap follow-up needs faster, safer, and less invasive techniques that can be easily correlated to clinical procedures. For this reason, we aimed to test the role of ultrahigh frequency ultrasound in follow-up of flap viability. Further on, we aimed to analyze if the chimeric groin flap can be mobilized in a sandwiched position without affecting its vascular supply by twisting its pedicle. METHODS: A total of 12 male Wistar rats, split into three groups, were used. Group A (n = 4) had the chimeric groin flap repositioned in a sandwich position on the anterior abdominal wall and underwent ultrahigh frequency ultrasound follow-up at days 10 and 14. Group B (n = 4) also had the flaps sandwiched, however, at day 14 the vascularity of flaps was proven by infusion of nontargeted ultrasound contrast agents, after which flaps were sent for histological analysis. Group C (C1 n = 2, C2 n = 2) was the control group. In C1 the chimeric groin flap was harvested and sent for histology on day 0, acting as a histological benchmark of flap viability, and in C2 the chimeric groin flap was re-sutured in its anatomical position and after 14 days, flaps were harvested and sent for histological analysis, acting as a direct control for Group B. RESULTS: Ultrasound showed constant vascular flow in both adipose and skin flaps in the sandwiched position. Microbubble study showed diffuse perfusion within flaps. Ultrasound measurements of flow velocity, flap volume, and percentage of vascularity showed a decrease in flap volume and increase in vascularity over 14 days. Histology showed similar viability in both groups. CONCLUSION: Ultrahigh frequency ultrasound may be a valuable tool for postoperative flap assessment, while the chimeric flap can be moved freely in a sandwich position making it suitable for adding tissue substitutes within its components.

Insight into Potential Biomedical Application of Mesoporous Materials.

The physicochemical properties of many drugs have a decisive impact on their bioavailability, as well as the pharmacokinetic efficiency in various disease therapeutics. That is why mesoporous materials have attracted a special interest in the drug delivery field, facilitating the loading of drugs into their pores due to their high surface area and porosity. The interfacial interactions established with drug molecules represent the driving force for efficient drug loading and controlled release kinetics. Moreover, these materials offer an optimal design for implantable local-delivery devices or for improving the accuracy of imaging techniques in clinical diagnosis. Their use is validated by improvements in therapeutic outcome and prevention of side effects. This review discusses the role of mesoporous materials in different biomedical applications.

Transcutaneous Drug Delivery Systems Based on Collagen/Polyurethane Composites Reinforced with Cellulose.

Designing composites based on natural polymers has attracted attention for more than a decade due to the possibility to manufacture medical devices which are biocompatible with the human body. Herein, we present some biomaterials made up of collagen, polyurethane, and cellulose doped with lignin and lignin-metal complex, which served as transcutaneous drug delivery systems. Compared with base material, the compressive strength and the elastic modulus of biocomposites comprising lignin or lignin-metal complex were significantly enhanced; thus, the compressive strength increased from 61.37 to 186.5 kPa, while the elastic modulus increased from 0.828 to 1.928 MPa. The release of ketokonazole from the polymer matrix follows a Korsmeyer-Peppas type kinetics with a Fickian diffusion. All materials tested were shown to be active against pathogenic microorganisms. The mucoadhesiveness, bioadhesiveness, mechanical resistance, release kinetic, and antimicrobial activity make these biocomposites to be candidates as potential systems for controlled drug release.

Ghrelin and its role in gastrointestinal tract tumors (Review).

Ghrelin, an orexigenic hormone, is a peptide that binds to the growth hormone secretagogue receptor; it is secreted mainly by enteroendocrine cells in the oxyntic glands of the stomach. Ghrelin serves a role in both local and systemic physiological processes, and is implicated in various pathologies, including neoplasia, with tissue expression in several types of malignancies in both in vitro and in vivo studies. However, the precise implications of the ghrelin axis in metastasis, invasion and cancer progression regulation has yet to be established. In the case of gastrointestinal (GI) tract malignancies, ghrelin has shown potential to become a prognostic factor or even a therapeutic target, although data in the literature are inconsistent and unsystematic, with reports untailored to a specific histological subtype of cancer or a particular localization. The evaluation of immunohistochemical expression shows a limited outlook owing to the low number of cases analyzed, and in vivo analyses have conflicting data regarding differences in ghrelin serum levels in patients with cancer. The aim of this review was to examine the relationship between ghrelin and GI tract malignancies to demonstrate the inconsistencies in current results and to highlight its clinical significance in the outcome of these patients.

GIST and Ghrelin: To Be or Not to Be?

BACKGROUND: Ghrelin is the orexigenic hormone secreted mainly by the stomach. Its involvement in neoplastic development has been studied in gastrointestinal adenocarcinomas. Our paper aims to evaluate the influence of the ghrelin axis in gastrointestinal stromal tumors (GISTs). MATERIALS AND METHODS: The study design included two groups of patients, 46 with gastric GISTs and 30 with obesity. Archived tissue samples were evaluated for the presence of gastritis and H. pylori. Immunohistochemical expression of ghrelin and its receptor (GHS-R) was assessed. RESULTS: All GISTs showed absent immunohistochemical expression for ghrelin, while GHS-R displayed a particular pattern, with notable differences in intensity (p = 0.0256) and percentage of stained cells (p < 0.00001) in the periphery vs. core of tumors. Positive ghrelin expression was lower in the gastric mucosa of the first group compared to the second group (p < 0.001). CONCLUSION: The ghrelin axis can influence GISTs carcinogenesis through activation of GHS-R. A previously described direct autocrine/paracrine mechanism is not supported by our findings.

Protective or Risk Factors for Postoperative Pancreatic Fistulas in Malignant Pathology.

INTRODUCTION: Malignant tumors are associated with a low incidence of postoperative pancreatic fistulas. The presence of peritumoral fibrosis is considered the protective factor for the development of postoperative pancreatic fistulas after pancreatic resections for pancreatic ductal adenocarcinomas. METHODS: We analyzed a series of 109 consecutive patients with pancreatic resections for malignant pathology: pancreatic ductal adenocarcinomas and periampullary adenocarcinomas. The incidence of postoperative pancreatic fistulas has been reported in tumor histological type, in the presence of peritumoral fibrosis, and in the association between adenocarcinomas and areas of acute pancreatitis. The data obtained were processed with the statistical analysis program SPSS, and statistically significant p were considered at a value <0.05. RESULTS: For the entire study group, the incidence of postoperative pancreatic fistulas was 11.01%. The lowest incidence was observed in the group of patients with pancreatic ductal adenocarcinomas (4.06% vs. 25.72% in the group with periampullary adenocarcinoma), with a p = 0.002. The presence of peritumoral fibrous tissue was observed in 49.31% of cases without pancreatic fistulas, and in 54.54% of cases that developed this postoperative complication (p = 0.5). Also, the peritumoral fibrous tissue had a uniform distribution depending on the main diagnosis (56.14% in pancreatic ductal adenocarcinoma group vs. 37.04% in periampullary adenocarcinoma group, with a p = 0.08). In the group of patients who associated areas of acute pancreatitis on the resections, the incidence of postoperative pancreatic fistulas was 7.8 times higher (30% vs. 3.8%, p = 0.026). CONCLUSIONS: Peritumoral fibrous tissue was not a factor involved in the developing of postoperative pancreatic fistulas. The association of adenocarciomas with areas of acute pancreatitis has led to a significant increase in postoperative pancreatic fistulas, which is a significant and independent risk factor.

New composites based on starch/Ecoflex®/biomass wastes: Mechanical, thermal, morphological and antimicrobial properties.

Different biomass wastes were successfully blended with starch and Ecoflex® viz. poly(butylene adipate-co-terephthalate), without glycerol addition, to obtain biocomposite materials. The mechanical properties, as well as thermal and surface properties, of the developed composites were evaluated. It was found that the tensile strength and impact strength improved upon the addition of lignin, while the water uptake capacity decreased. The presence of 5% lignin determined an increase in tensile strength of 125.4% for materials comprising celery (CEL), 109.6% for materials comprising poplar seed hair fibers (PSH), 92.9% for materials comprising pomace (POM) and 127.7% for materials comprising Asclepias syriaca fibers (ASF), compared with a reference sample. The addition of lignin to all the formulations conferred good antimicrobial properties against different microorganisms, S. aureus and especially E. coli. The good mechanical properties, water resistance and antimicrobial activity against pathogens recommend these composites to be used in the manufacture of packaging materials.

Terahertz Spectroscopy and Imaging: A Cutting-Edge Method for Diagnosing Digestive Cancers.

The Terahertz's wavelength is located between the microwave and the infrared region of the electromagnetic spectrum. Because it is non-ionizing and non-invasive, Terahertz (THz)-based detection represents a very attractive tool for repeated assessments, patient monitoring, and follow-up. Cancer acts as the second leading cause of death in many regions, and current predictions estimate a continuous increasing trend. Of all types of tumors, digestive cancers represent an important percentage and their incidence is expected to increase more rapidly than other tumor types due to unhealthy lifestyle habits. Because it can precisely differentiate between different types of molecules, depending on water content, the information obtained through THz-based scanning could have several uses in the management of cancer patients and, more importantly, in the early detection of different solid tumors. The purpose of this manuscript is to offer a comprehensive overview of current data available on THz-based detection for digestive cancers. It summarizes the characteristics of THz waves and their interaction with tissues and subsequently presents available THz-based technologies (THz spectroscopy, THz-tomography, and THZ-endoscope) and their potential for future clinical use. The third part of the review is focused on highlighting current in vitro and in vivo research progress in the field, for identifying specific digestive cancers known as oral, esophageal, gastric, colonic, hepatic, and pancreatic tumors.

Role of mucosal high-risk human papillomavirus types in head and neck cancers in Romania.

BACKGROUND: Limited information is available about the involvement of human papillomavirus (HPV) in head and neck squamous cell carcinomas (HNSCCs) in Romanian patients. OBJECTIVE: To evaluate the HPV-attributable fraction in HNSCCs collected in Northeastern Romania. MATERIALS AND METHODS: In total, 189 formalin-fixed paraffin-embedded tissue samples (99 oral cavity tumors, 28 oropharynx, 48 pharynx, and 14 larynx/hypopharynx) were analyzed for HPV DNA and RNA using Luminex-based assays, and for overexpression of p16INK4a (p16) by immunohistochemistry. RESULTS: Of the 189 cases, 23 (12.2%) were HPV DNA-positive, comprising half of the oropharyngeal cases (14/28, 50.0%) and 9/161 (5.6%) of the non-oropharyngeal cases. HPV16 was the most prevalent HPV type (20/23, 86.9%), followed by HPV18 (5/23, 21.7%) and HPV39 (1/23, 4.3%). Only two (2/189, 1.1%) HNSCC cases were HPV-driven, i.e. positive for both HPV DNA and RNA. CONCLUSION: A very small subset of HNSCC cases within this cohort from Northeastern Romania appeared to be HPV-driven.