Cardiotoxicity in HER2-positive breast cancer patients.

Due to the recent advances in diagnosis and management of patients with HER2-positive breast cancer, especially through novel HER2-targeted agents, cardiotoxicity becomes an emerging problem. Although chemotherapy significantly increases survival, the risk of cardiovascular disease development is high and still underestimated and could imply treatment discontinuation. Frequently, due to lack of rigorous diagnosis strategies, cardiotoxicity assessment is delayed, and, moreover, the efficacy of current therapy options in restoring heart function is questionable. For a comprehensive risk assessment, it is vital to characterize the clinical spectrum of HER2-targeted agents and anthracyclines, as well as their pathogenic pathways involved in cardiotoxicity. Advanced cardiovascular multimodal imaging and circulating biomarkers plays primary roles in early assessing cardiotoxicity and also in guiding specific preventive measures. Even though the knowledge in this field is rapidly expanding, there are still questions that arise regarding the optimal approach in terms of timing and methods. The aim of the current review aims to providean overview of currently available data.

Automatic Detection of Colorectal Polyps Using Transfer Learning.

Colorectal cancer is the second leading cause of cancer death and ranks third worldwide in diagnosed malignant pathologies (1.36 million new cases annually). An increase in the diversity of treatment options as well as a rising population require novel diagnostic tools. Current diagnostics involve critical human thinking, but the decisional process loses accuracy due to the increased number of modulatory factors involved. The proposed computer-aided diagnosis system analyses each colonoscopy and provides predictions that will help the clinician to make the right decisions. Artificial intelligence is included in the system both offline and online image processing tools. Aiming to improve the diagnostic process of colon cancer patients, an application was built that allows the easiest and most intuitive interaction between medical staff and the proposed diagnosis system. The developed tool uses two networks. The first, a convolutional neural network, is capable of classifying eight classes of tissue with a sensitivity of 98.13% and an F1 score of 98.14%, while the second network, based on semantic segmentation, can identify the malignant areas with a Jaccard index of 75.18%. The results could have a direct impact on personalised medicine combining clinical knowledge with the computing power of intelligent algorithms.

Recent Advances in Nanoparticle-Mediated Diagnosis and the Treatment of Pancreatic Cancer.

Pancreatic cancer (PC), one of the most lethal solid tumors in humans, has a five-year survival rate of only 4%. Surgical treatment is the only accepted therapy with curative intent because the vast majority of these tumors are chemoresistant. Unfortunately, due to the aggressive nature of these tumors, fewer than 20% are resectable when the first symptoms occur. Novel therapies are required to overcome all these therapeutic issues, and the development of active nanocarriers represents an exciting opportunity to improve PC outcomes. The present review focuses on recent advances in the field of nanotechnology with application in PC treatment.

Carbon nanotubes as anti-bacterial agents.

Multidrug-resistant bacterial infections that have evolved via natural selection have increased alarmingly at a global level. Thus, there is a strong need for the development of novel antibiotics for the treatment of these infections. Functionalized carbon nanotubes through their unique properties hold great promise in the fight against multidrug-resistant bacterial infections. This new family of nanovectors for therapeutic delivery proved to be innovative and efficient for the transport and cellular translocation of therapeutic molecules. The current review examines the latest progress in the antibacterial activity of carbon nanotubes and their composites.

An Attempt to Build a National Prospective Electronic Database for Pancreaticoduodenectomies in Romania - Preliminary Results of the First Year Enrollment.

Introduction: National databases for pancreaticoduodenectomies (PD) have contributed to better postoperative outcomes after such complex surgical procedure because the multicentre collection of data allowed more reliable analyses with quality assessment and further improvement of technical issues and perioperative management. The current practice and outcomes after PD are poorly known in Romania because there was no national database for these patients. Thus, in 2016 a national-intent electronic registry for PD was proposed for all Romanian surgical centers. The study aims to present the preliminary results of this national-intent registry for PD after one-year enrollment. Patients Methods: The database was started on October 1st, 2016. Data were prospectively collected with an electronic online form including 102 items for each patient. The registry was opened to all the Departments of Surgery from Romania performing PD, with no restriction. Results: During the first year of enrollment were collected the data of 181 patients with PD performed by 24 surgeons from four surgical centers. The age of patients was 64 years (28 - 81 years), with slightly male predominance (61.3%). Computed tomography was the main preoperative imaging investigation (84.5%). All the PDs were performed by an open approach. The Whipple technique was used in 53% of patients, and a venous resection was required in 14.3% of cases. A posterior approach PD was considered in 16.6% of patients. The stomach was used to treat the distal remnant pancreas in 50.1% of patients. The operative time was 285 min (110 - 615 min), and the estimated blood loss was 400 ml (80 - 3000 ml). The overall morbidity rate was 55.8%, with severe (i.e., grade III-IV Dindo-Clavien) morbidity rate of 10%, and 3.9% in-hospital mortality rate. The overall pancreatic fistula, delayed gastric emptying and hemorrhage rates were 19.9%, 39.8% and 15.5%. Periampullary malignancies were the main indications for PD (78.9%), with pancreatic cancer on the top (48%). Conclusions: To build a prospective electronic online database for PD in Romania appears to be a feasible project and a useful tool to know the current practice and outcomes after PD in our country. However, improvements are still required to encourage a larger number of surgical centers to introduce the data of patients with PD.

Development of nanoparticle-based optical sensors for pathogenic bacterial detection.

BACKGROUND: Pathogenic bacteria contribute to various globally important diseases, killing millions of people each year. Various fields of medicine currently benefit from or may potentially benefit from the use of nanotechnology applications, in which there is growing interest. Disease-related biomarkers can be rapidly and directly detected by nanostructures, such as nanowires, nanotubes, nanoparticles, cantilevers, microarrays, and nanoarrays, as part of an accurate process characterized by lower sample consumption and considerably higher sensitivity. There is a need for accurate techniques for pathogenic bacteria identification and detection to allow the prevention and management of pathogenic diseases and to assure food safety. CONCLUSION: The focus of this review is on the current nanoparticle-based techniques for pathogenic bacterial identification and detection using these applications.

Rational design of gold nanocarrier for the delivery of JAG-1 peptide.

BACKGROUND: Unique properties exhibited by nanoparticles makes them great candidates for applications in physics, chemistry, biology, material science and medicine. The biological applications of water-soluble gold nanoparticles range from contrast agents, delivery vehicles to therapeutics. Notch signaling is a complex network that orchestrates cell fate decisions, which involves proliferation, migration, differentiation and cell death in organisms ranging from insects to humans. Studies have showed that a correct orientation of the Jag-1 signalling protein on the substrates proves to be of great importance when promoting Jagged-1 Notch interactions, also the availability of the ligands, super cedes the importance of their concentration. RESULTS: The aim of the present study was to synthetize a Jag-1 functionalized nanocarrier, which would promote an efficient interaction between the Jag-1 peptide and the Notch receptor. To this end, two routes for gold nanoparticle-peptide assembly were investigated, and the synthetized bio-nanostructures were characterized and compared by means of UV-Vis, FT-IR, DLS and AFM techniques. CONCLUSIONS: We have obtained a stable, monodisperse, hetero-functionalized GNP-PEG-JAG-1 bio-nanostructure for Notch pathway activation applications.

Laparoscopic rectal resection versus conventional open approach for rectal cancer - a 4-year experience of a single center.

PURPOSE: This study was carried out to compare the therapeutic outcomes and complications of the laparoscopic and the conventional open surgery technique used for treating rectal cancer. Another goal was to find the fastest and most accurate method of treatment for rectal cancer, along with establishing the advantages and disadvantages of the two surgical techniques, depending on cancer location and its stage. METHODS: A total of 172 patients diagnosed with rectal cancer and hospitalized in the Department of Surgery III between January 1st 2008 and December 31st 2011 were studied. The laparoscopic approach was performed on 29 (16.8%) patients, and the remaining 143 (83.2%) underwent the conventional Miles/Lloyd-Davies abdominoperineal resection. A longitudinal study was conducted on patients with rectal resection, the used data being obtained from the database of the Department of Surgery III, hospital records, protocols and clinical charts of rectal cancer cases. RESULTS: There were no statistically significant differences regarding symptoms, gender, age, body mass index (BMI), tumor site, TNM stage, intraoperative accidents, operative time, and postoperative mortality between the two groups. The laparoscopic group presented advantages regarding antibiotic and analgesic therapy, early mobilization, hospital stay, intraoperative blood loss, resuming oral nutrition, bowel transit resumption, postoperative complications and wound complications. CONCLUSION: Laparoscopic abdominoperineal resection for rectal cancer is feasible, safe and effective. It can be safely performed by an experienced team, reducing the rate of postoperative complications, the need for blood transfusions, the adminstration of antibiotics and painkillers, allowing faster bowel transit resumption, shortening hospital stay and providing superior aesthetic results.

Role of Biofunctionalized Nanoparticles in Digestive Cancer Vaccine Development.

Nanotechnology has provided an opportunity for unparalleled development of the treatment of various severe diseases. The unique properties of nanoparticles offer a promising strategy for enhancing antitumor immunity by enhancing immunogenicity and presentation of tumor autoantigens for cancer immunotherapy. Polymeric, liposomal, carbon or silica-based nanoparticles are among those with major immunomodulatory roles in various cancer treatments. Cancer vaccines, in particular digestive cancer vaccines, have been researched and developed on nanotechnological platforms. Due to their safety, controlled release, targeting of dendritic cells (DCs) and improved antigen uptake, as well as enhanced immunogenicity, nanoparticles have been used as carriers, as adjuvants for increased effect at the tumor level, for their immunomodulating effect, or for targeting the tumor microenvironment, thereby increasing tumor immunogenicity and reducing tumor inflammatory response. This review looks at digestive cancer vaccines developed on nanoparticle platforms and the impact nanoparticles have on the effects of these vaccines.

In vitro photothermal therapy of pancreatic cancer mediated by immunoglobulin G-functionalized silver nanoparticles.

Pancreatic cancer is one of the most aggressive forms of cancer, and treatment options are limited. One therapeutic approach is to use nanoparticles to deliver the active agent directly to pancreatic cancer cells. Nanoparticles can be designed to specifically target cancer cells, minimizing damage to healthy tissues. Silver nanoparticles have the unique ability to absorb light, especially in the near-infrared (NIR) region. In this study, silver nanoparticles functionalized with IgG molecules were synthesized and administered to pancreatic cancer cell lines. Subsequently, the cells were photo-excited using a 2 W 808 nm laser and further examined in PANC-1 pancreatic cancer cell lines. Flow cytometry and confocal microscopy combined with immunochemical staining were used to examine the interaction between photo-excited silver nanoparticles and pancreatic cancer cells. The photothermal therapy based on IgG-functionalized silver nanoparticles in pancreatic cancer induces dysfunction in the Golgi apparatus, leading to the activation of the caspase-3 apoptotic pathway and ultimately resulting in cellular apoptosis. These findings suggest that our proposed IgG nanoparticle laser treatment could emerge as a novel approach for the therapy of pancreatic cancer.

Open or laparoscopic treatment for hydatid disease of the liver? A 10-year single-institution experience.

BACKGROUND: Selection of the most appropriate treatment to obtain the lowest morbidity, mortality, and recurrence rates is mandatory for hydatid disease of the liver. This study evaluated the results of laparoscopic treatment (compared with the open approach) in the context of a 10-year single-institution experience. METHODS: Between January 1998 and January 2008, 333 patients with hydatid disease of the liver underwent surgery in the authors' department. Only the following aspects were considered as selection criteria for laparoscopic surgery: liver cyst not located in segment 1 or 7, with corticalization on the surface and no evidence of intrabiliary rupture. Of 62 patients who underwent laparoscopic treatment, 3 required conversion to open surgery. The remaining 59 patients (group 1) were analyzed. During the same period, 271 patients with hepatic hydatid disease underwent conventional surgery, but only 172 records were compatible with the criteria for the laparoscopic approach and the respective patients were retrospectively reviewed (group 2). RESULTS: Conversion to open surgery occurred in three cases (4.84 %). The mean cyst diameter was 6.62 cm (range, 2-15 cm) in group 1 and 7.23 cm (range, 2-18 cm) in group 2 (p = 0.699). The mean operative time was 72 min (range, 45-140 min) in group 1 and 65 min (range, 35-120 min) in group 2 (p < 0.001). The general complication rate and abdominal wound complication rate were respectively 0 % and 0 % in group 1 (p = 0.023) compared with 5.23 and 8.72 % in group 2 (p = 0.015). The mean hospital stay was 6.42 days (range, 1-21 days) in group 1 and 11.7 days (range, 4-80 days) in group 2 (p < 0.001). The mean follow-up period was 24.2 months (range, 6-32 months) in group 1 and 28.4 months (range, 6-40 months) in group 2. No recurrences were observed in either group during this period. CONCLUSION: Laparoscopic surgery provides a safe and efficacious approach for almost all types of hepatic hydatid cysts. Large, prospective, randomized trials are needed to confirm its superiority.

Ethinylestradiol30µg-drospirenone and metformin: could this combination improve endothelial dysfunction in polycystic ovary syndrome?

BACKGROUND: We are hereby investigating for the first time the effect of the association ethinylestradiol30µg-drospirenone 3mg (DRP/EE30µg) plus metformin and weight loss on endothelial status and C-reactive protein (hsCRP) levels in polycystic ovary syndrome (PCOS). METHODS: 25 young women with PCOS (mean age 22.76 ± 0.83 years, body mass index (BMI): 28.44 ± 6.23) who completed the study were prospectively evaluated. The oral contraceptive- DRP/EE30µg (21 days/month) and metformin (1700 mg daily) were administered for 6 months to the PCOS group. Additionally, the 15 overweight and obese patients (BMI > 25 kg/m2) were instructed in a diet of no more than 1500 cal daily. Primary outcome measures were surrogate markers of cardiovascular disease and included endothelial function, i.e. flow-mediated dilatation (FMD) on the brachial artery and endothelin-1 levels, as well as hsCRP concentrations, body composition (measured by whole-body dual-energy X-ray-absorptiometry) and insulin resistance. Variables were assessed at baseline, as well as after our medical intervention. RESULTS: The combination between DRP/EE30µg plus metformin combined with weight loss triggered a significant improvement in the FMD values (FMD-PCOSbasal 3.48 ± 1.00 vs FMD-PCOS6 months7.43 ± 1.04, p = 0.033), as well as body composition and insulin insensitivity (p < 0.05). Regarding hsCRP levels, there was no significant intragroup (PCOS6months - PCOSbasal) difference. CONCLUSION: A 6-month course of metformin- DRP/EE30µg (associated with weight loss) improves the endothelial dysfunction in PCOS and shows neutral effects on hsCRP concentrations as an inflammation marker. These data demand for reevaluation of the medical therapy in PCOS, particularly in women with additional metabolic and cardiovascular risk factors (ClinicalTrials.gov Identifier: NCT01459445).

Laparoscopic low anterior resection with total mesorectal excision for rectal cancer.

Rectal resections are the only treatment with curative intent currently accepted world wide. When performed in elective circumstances, laparoscopic rectal excision is technically feasible in surgical approach of mid-rectal cancer in a considerable number of patients. There are many benefits of the laparoscopic approach to rectal resection such as short hospitalization, less pain, less postoperative complications and improved quality of life. However, one mandatory condition in laparoscopic resection of rectum includes complete excision of the rectum and mesorectum, generally ensuring a minimal distal margin of 2cm and circumferential radial clearance before performing a coloanal anastomosis. Here, we present a laparoscopic approach for rectal cancer treatment consisting in a wide resection of the rectum, including the entire fascia with the enclosed mesentery of the rectum.

Thoracoscopic and laparoscopic esophagectomy with cervical manual anastomosis for esophageal cancer.

Evidence on the benefits of minimally invasive approach over traditional open procedure in gastrointestinal surgery is continuing to accumulate. This is also the case for esophageal surgery.Although laparoscopic esophageal surgery was initially reserved for benign pathology, the technical development, increasing experience with laparoscopic and thoracoscopic techniques and the theoretical advantages of minimally invasive surgery have widened the scope of minimally invasive approach to esophageal cancer. The surgical treatment of esophageal cancer often requires extensive procedures and is therefore, considered one of the most challenging and invasive procedure of gastrointestinal surgery. While transhiatal and transthoracic esophagectomy are common approaches for esophageal resection, data regarding the combined thoracoscopic and laparoscopic approach to esophagectomy are limited. The minimally invasive technique of esophagectomy to be described consists of three phases: thoracoscopic esophageal mobilization and mediastinal lymphadenectomy followed by laparoscopic gastric mobilization, abdominal lymphadenectomy and gastric conduit formation and finally retrieval of the resection specimen followed by an esophagogastric anastomosis via a left cervical incision.

Carbon Nanotubes-Based Assays for Cancer Detection and Screening.

Carbon nanotubes (CNTs) were considered a potential cargo for cancer therapy and diagnosis following researchers' shared goal of finding a new delivery system to enhance the pharmacological performance of the administered drugs. To date, several excellent reviews have focused on the role of CNTs as drug delivery systems, although there is currently no existing study that gathers all the advances in research-connected carbon nanotubes-based assay development for the early detection of cancer. In this review article, we will focus on the emerging role of CNTs as anticancer detection agents.

Surgical Management of Gastric Cancer: A Systematic Review.

Gastric cancer is the fifth most common cancer worldwide, and it is responsible for 7.7% of all cancer deaths. Despite advances in the field of oncology, where radiotherapy, neo and adjuvant chemotherapy may improve the outcome, the only treatment with curative intent is represented by surgery as part of a multimodal therapy. Two concepts may be adopted in appropriate cases, neoadjuvant treatment before gastrectomy (G) or primary surgical resection followed by chemotherapy. Such an approach, combined with early detection and better screening, has led to a decrease in the overall incidence of gastric cancer. Unfortunately, malignant tumors of the stomach are often diagnosed in locally advanced or metastatic stages when the median overall survival remains poor. Surgical care in these cases must be provided by a multidisciplinary team in a high-volume center. Important surgical aspects such as optimum resection margins, surgical technique, and number of harvested lymph nodes are important factors for patient outcomes. The standardization of surgical treatment of gastric cancer in accordance with the patient's profile is of decisive importance for a better outcome. This review aims to summarize the current standards in the surgical treatment of gastric cancer.

Artificial Intelligence in Colorectal Cancer Diagnosis Using Clinical Data: Non-Invasive Approach.

Colorectal cancer is the third most common and second most lethal tumor globally, causing 900,000 deaths annually. In this research, a computer aided diagnosis system was designed that detects colorectal cancer, using an innovative dataset composing of both numeric (blood and urine analysis) and qualitative data (living environment of the patient, tumor position, T, N, M, Dukes classification, associated pathology, technical approach, complications, incidents, ultrasonography-dimensions as well as localization). The intelligent computer aided colorectal cancer diagnosis system was designed using different machine learning techniques, such as classification and shallow and deep neural networks. The maximum accuracy obtained from solving the binary classification problem with traditional machine learning algorithms was 77.8%. However, the regression problem solved with deep neural networks yielded with significantly better performance in terms of mean squared error minimization, reaching the value of 0.0000529.

Modelling in Synthesis and Optimization of Active Vaccinal Components.

Cancer is the second leading cause of mortality worldwide, behind heart diseases, accounting for 10 million deaths each year. This study focusses on adenocarcinoma, which is a target of a number of anticancer therapies presently being tested in medical and pharmaceutical studies. The innovative study for a therapeutic vaccine comprises the investigation of gold nanoparticles and their influence on the immune response for the annihilation of cancer cells. The model is intended to be realized using Quantitative-Structure Activity Relationship (QSAR) methods, explicitly artificial neural networks combined with fuzzy rules, to enhance automated properties of neural nets with human perception characteristics. Image processing techniques such as morphological transformations and watershed segmentation are used to extract and calculate certain molecular characteristics from hyperspectral images. The quantification of single-cell properties is one of the key resolutions, representing the treatment efficiency in therapy of colon and rectum cancerous conditions. This was accomplished by using manually counted cells as a reference point for comparing segmentation results. The early findings acquired are conclusive for further study; thus, the extracted features will be used in the feature optimization process first, followed by neural network building of the required model.

Biomarkers in Pancreatic Cancer as Analytic Targets for Nanomediated Imaging and Therapy.

As the increase in therapeutic and imaging technologies is swiftly improving survival chances for cancer patients, pancreatic cancer (PC) still has a grim prognosis and a rising incidence. Practically everything distinguishing for this type of malignancy makes it challenging to treat: no approved method for early detection, extended asymptomatic state, limited treatment options, poor chemotherapy response and dense tumor stroma that impedes drug delivery. We provide a narrative review of our main findings in the field of nanoparticle directed treatment for PC, with a focus on biomarker targeted delivery. By reducing drug toxicity, increasing their tumor accumulation, ability to modulate tumor microenvironment and even improve imaging contrast, it seems that nanotechnology may one day give hope for better outcome in pancreatic cancer. Further conjugating nanoparticles with biomarkers that are overexpressed amplifies the benefits mentioned, with potential increase in survival and treatment response.

Cytotoxicity and biological effects of functional nanomaterials delivered to various cell lines.

Functional nanomaterials that included gold, silver nanoparticles and single wall carbon nanotubes were delivered to two cell lines (MLO-Y4 osteocytic cells and HeLa cervical cancer cells) in various concentrations. The cells were found to uptake the nanomaterials in a relatively short time, a process that significantly affected the shape and the size of the cells. The percentage of cellular death, due to the delivery of these nanomaterials, was found to be the highest for carbon nanotubes and increased gradually with the concentration of these nanostructures. Moreover, when the nanomaterials were delivered to the cells combined with commonly used chemotherapeutic agents such as etoposide or dexamethasone, the number of the cells that died increased significantly (100-300%) as compared with the case when only the nanomaterials or the chemotherapeutic agents were delivered. The experimental results were confirmed by Caspase 3 studies, indicating a strong interaction between the nanomaterials used in this study and the protein structure of the cells, which allowed a more effective action of the apoptotic agents. These findings could be the foundation of a new class of cancer therapies that are composed of both chemotherapeutic agents and nanomaterials.