Molecular Profiling of EGFR Status to Identify Skin Toxicity in Colorectal Cancer: A Clinicopathological Review.

Colorectal cancer (CRC) represents an important health problem, being the third most common type of cancer. In Romania, the CRC incidence has doubled over the years. Both environmental factors and genetic susceptibility are very important for the pathogenesis of CRC. The epidermal growth factor receptor (EGFR) plays an extremely important role in CRC tumorigenesis. Overexpression or dysregulation of EGFR pathway molecules are frequently associated with tumor aggressiveness and patient response to treatment. Based on these considerations, EGFR became one of the first targets of molecular therapies used in CRC. At present, cetuximab and panitumumab are considered to be essential in the treatment of patients with metastatic colorectal cancer expressing the KRAS wild-type gene and EGFR. The main adverse effect for both cetuximab and panitumumab is skin toxicity, present in approximately 80% of patients. The risk of secondary infections, in particular of bacterial infections, is also increased. Cases of staphylococcal infection associated with skin peeling, cellulite, erysipelas, and even Staphylococcus sepsis, were reported. For a long time cutaneous toxicity has been a positive predictor in the efficacy of anti-EGFR treatment, but compliance with treatment and the quality of life of patients with metastatic CRC decreases in the presence of these skin reactions. That is why we emphasize the necessity and importance of using a modern method (molecular analysis of gene polymorphisms possibly supplemented by targeted confocal laser endomicroscopy) to identify a molecular diagnosis, in order to foresee and prevent the appearance of skin reactions and to manage skin toxicity.

The Significance of Right Ventricle in Young Subjects with Diabetes Mellitus Type 1. An echocardiographyic study.

BACKGROUND: Diabetes mellitus type 1 (DM1) is associated with high risk for cardiovascular disease and early detection of myocardial dysfunction is very important for the prevention of cardiac complications. Although the functionality of right ventricule is important in a lot of disease affecting long time prognosis and progression, in diabetic type 1 patients has not been studied in depth yet. OBJECTIVES: To evaluate the right ventricular function by using both conventional echocardiography as well as speckle tracking echocardiography (STE) in young adults with diabetes mellitus type 1. METHODS: We included 60 young asymptomatic adults diagnosed with diabetes mellitus type 1 (mean interval from diagnosis 9±6 years) and 90 healthy controls. Conventional and STE Echocardiography was acquired using the GE Vivid S60 equipment. The longitudinal right ventricular strain 6 segments (RV GLS global) and 3 segments (RVFW GLS) of right ventricle (RV GLSbazal, RV GLSmid, RV GLSapex) as well were obtained using the EchoPAC BT13 workstation. RESULTS: No significant intergroup differences in EF were noted. Conventional echocardiographic parameters revealed lower tricuspid annular velocities Et, At and Et/At ratio compared to controls suggesting a diastolic disfunction in diabetes group. RV speckle tracking strain measurements showed no significant difference between the groups. CONCLUSIONS: Young adults with type 1 diabetes mellitus and without known heart disease have diastolic right ventricular dysfunction. The subclinical myocardial systolic function is preserved in early stages.

No Interval Cancers in Endoscopic Practice.

Colonoscopy is long time the most preferred method for CRC screening along with diagnosis and treatment for a range of colon diseases. Based on its difficulty in visualizing precursor CRC lesions, mostly those located on the right colon, this method can be subject of improvement. The colonoscopy quality can be influenced by many factors such as colon preparation, retraction time, the colonoscopists medical training and knowledges as well as the performance of endoscopy equipment. The bad quality of colonoscopy will result in the emergence of interval cancers defined, based on the author, as cancers that appear at 3-5 years up to 10 years from the colonoscopy procedure. Interval cancers have predominantly incriminated both the colonoscopy quality and the clinician competences and less the tumor biology. Subsequently there were set quality indicators of colonoscopy in order to raise the quality of the exploration. Among the important indicators, proving their utility in studies, the ADR (adenoma detection rate) is most commonly used along with PDR (polyp detection rate) and APC (adenoma per colonoscopy). Following the purpose of obtaining a higher colonoscopy quality the medical units should keep in check all indicators. Furthermore, there should be an active involvement in an additional training of non-conforming medical personnel or even restrain of practice, given the medical legal actions that have interval cancers as a main cause.

Assessment of the Quality of Outpatient Endoscopic Procedures by Using a Patient Satisfaction Questionnaire.

INTRODUCTION: Endoscopic procedures represent an important part of daily practice, both for gastroenterologists and nurses, enabling diagnosis and treatment of digestive diseases. An optimal level of quality needs to be obtained for endoscopic procedures to be efficient, which is reflected directly by patient satisfaction. The Gastrointestinal Endoscopy Satisfaction Questionnaire (GESQ) has already been validated in a multicenter trial as an efficient method for measuring patient satisfaction. Aim The aim of our study was to evaluate the quality of endoscopic procedures and patient satisfaction by applying a modified version of the GESQ in an outpatient facility, with or without deep sedation performed under the supervision of an anesthesiologist. MATERIAL AND METHODS: Our study included 552 patients undergoing diagnostic and therapeutic upper and lower GI endoscopies, including endoscopic ultrasound procedures (EUS) performed under propofol sedation, from September 2015 to February 2016. Consecutive patients examined during these 6 months received the questionnaire which was handed by the endoscopy nurse two hours after procedure. The GESQ was modified to include different sections for: 1) communication skills with questions regarding the quantity and clarity of the information delivered to the patient before and after the procedures; 2) pain and discomfort related to the examination with an added question about the specific procedure the patient had undergone; 3) staff manners; 4) physician's technical skills; 5) facility organization (waiting time, comfort in the recovery room, good facilities and equipment) and 6) overall satisfaction. The questionnaire did not include personal data, while answers were analyzed in a confidential manner. RESULTS: A total number of 552 patients agreed to answer our questionnaire, 192 (34,7%) underwent gastroscopies, 288 (52,1%) colonoscopies and 72 (13,2%) EUS examinations. Regarding the overall level of satisfaction (assessed on a five-point scale), 476 (86,2%) were very satisfied or satisfied, 69 (12,5%) dissatisfied and the remainder 7 (1,3%) were indifferently. For the communication section 16 (3%) patients were not satisfied with the explanations received before the procedure or with the answers to their questions. Pain and discomfort were mentioned by 29 (5,2%) of the patients, usually related to colonoscopies or EUS examinations. 13 (2,3%) of the patients considered the comfort or intimacy of the recovery room to be poor, and 11 (2%) patients were not satisfied with the waiting time before the procedure. CONCLUSION: Our modified questionnaire showed good overall patient satisfaction with our endoscopy unit, while also suggesting some areas in need of improvement, such as staff communication skills, better time management and reorganization of the recovery area. Our study demonstrates the importance of such questionnaires in providing feedback information meant to improve standards in endoscopy, including staff skills and organization.

Recent Developments in Tele-Ultrasonography.

A long-standing trend that will continue to grow in healthcare is providing high quality services for all the patient, no matter the distance and no matter the place. One approach currently being used to increase population access to healthcare services is telemedicine. This narrative review presents one branch of e-health, in particular the use of teleultrasonography (TUS) in clinical practice, the challenges and barriers encountered. Current advances in ultrasound technology, including the growth of portable and small ultrasound devices have increased the range of applications of TUS, from traumatic patients in emergency medicine, maternal ultrasound and even for monitoring and screening for chronic illnesses. Even though some barriers are still looking for a solution, like standardized training and protocols, errors in data acquisition, the lack of trained professionals to operate in remote areas, TUS has the potential to redesign future health care systems.

A Diagnostic Challenge: Pancreatic Cancer or Autoimmune Pancreatitis?

We report a rare case of seronegative autoimmune pancreatitis (AIP) that presented as a pancreatic focal lesion and was considered to be pancreatic cancer based on the clinical presentation and imaging findings. The endoscopic ultrasound-guided biopsies of the pancreatic mass revealed no malignant cells and the pancreatic swelling had become diffuse on repeat imaging. AIP was suspected and a trial of steroids was considered as a diagnostic and therapeutic method. The patient responded dramatically to corticosteroid treatment with resolution of symptoms and normal imagining and laboratory parameters. This case highlights the challenge in the diagnostic approach of a pancreatic mass.

A Primary Retroperitoneal Diffuse Large B-Cell Lymphoma: A Challenging Diagnosis.

Although quite rare, retroperitoneum can harbour malignant limphomas. On the grounds that the anatomical location is uncommon and the symptoms are scarce, the diagnosis is usually late and challenging. Imaging methods such as magnetic resonance imaging, computed tomography (CT) and positron emission tomography-computed tomography (PET-CT), can characterize and locate the tumor while endoscopic ultrasound fine needle aspiration (EUS-FNA) may provide pathological confirmation. We present the clinical case of a fifty-five-year-old female that is admitted to our hospital with epigastric discomfort, nausea and vomiting. CT showed a homogenously enhancing mass lesion that encased the pancreas, in contact with the portal vein, inferior vena cava, invading splenomesenteric confluence. To investigate further, EUS-FNA was decided and it revealed lymphocyte proliferation suggestive for the diagnosis of lymphoma. Hereinafter, surgical intervention was performed and immunohistochemical analysis and sub classification of lymphoma was obtained. The final diagnosis was non-Hodgkin lymphoma, Diffuse Large B-Cell Lymphoma (DLBCL). Poly-chemotherapy with R-CHOP was initiated. At the end of the treatment fluorodeoxyglucose positron emission tomography (FDG-PET) was performed and no pathological findings were found. A brief review of literature is also provided.

Periprocedural Role of Nurses During Interventional Endoscopic Procedures Under Deep Sedation.

BACKGROUND: Most of endoscopic procedures, either diagnostic or therapeutic, are nowadays performed under sedation, used as a standard practice in most of the centers. Consequently, the number and complexity of endoscopic procedures has increased as sedation diminishes anxiety and discomfort for patients, also improving the quality of endoscopic examinations, and outcomes in therapeutic endoscopy. Compared to standard diagnostic upper or lower GI endoscopy, endoscopic ultrasound (EUS) and endoscopic retrograde cholangiopancreatography (ERCP) are often longer and more complicated procedures, thus requiring higher doses of sedatives. Sedation levels and medication types depend on a variety of factors, related both to patient characteristics (age, comorbidities, preference, etc.), and procedure types (simple diagnostic endoscopy or more complex therapeutic procedures). Propofol has become undoubtedly the induction agent of choice as it is easy to administer, enables prompt awakening, and has fewer side effects. AIM: The aim of this paper is to outline the role and efficacy of the endoscopy nurse in the peri-procedural care of patients undergoing complex therapeutic interventions (EUS-guided and/or ERCP) under propofol sedation. METHODS: At our institution, the Research Centre of Gastroenterology and Hepatology Craiova, 192 patients underwent interventional endoscopic procedures between January 2014-December 2014 (130 EUS and 62 ERCP) under sedation with propofol. We included 110 patients in our study that were followed-up between 4 to 6 hours after the procedures. The GI nurse was responsible that the patients and/or their accompanying persons receive proper information in both written and spoken form regarding their procedure and potential adverse events after sedation. After the procedures the side effects related to anesthesia were marked down by the GI nurse based on a standard questionnaire. RESULTS: The patients mean age was 53.5 years old, with 46 (41.8%) women and 64 (58.2%) men. Most of the patients, that is 90 (81.8%), presented no adverse events. The other 20 patients (18.2%) had the following side effects from sedation: drowsiness in 5 (4.5%) of the cases, nausea in 3 cases (2.8%), vomiting in one case (0.9%), 2 (1.8%) of the patients presented dizziness, 2 (1.8%) headache, 3 (2.8%) coughing, only one patient (0.9%) had an injection site reaction, one (0.9%) had shivers, and 2 patients (1.8%) presented bradycardia. Patients that had side effects were mainly of advanced age and with associated diseases which included chronic kidney disease, cardio-vascular diseases. The nurse responsible with the follow-up of patients was able to rapidly assess their complaints and intervene to the benefit of the patient, before serious adverse events could occur. CONCLUSIONS: Although propofol sedations is generally considered safe, potential side effects should be held in mind. The GI nurse has a valuable role in monitoring patients and assessing their response to sedation after the procedure, as well as in timely stepping in where necessary to prevent further complications.

Staging with computed tomography of patients with colon cancer.

PURPOSE: Accurate staging of colonic cancer is important for patient stratification. We aimed to correlate the diagnostic accuracy of preoperative computed tomography (CT) with final histopathology as reference standard. METHODS: Data was collected retrospectively on 615 consecutive patients operated for colonic cancer. Evaluation was based upon T-stage. Patients were stratified into high-risk and low-risk groups, based on the extent of tumor invasion beyond the proper muscle layer of more or less than 5 mm. The Kendall tau correlation coefficient was used to calculate concordance between radiological (r)T-stage obtained at CT imaging and pathological (p)T-stage from the final pathology. RESULTS: In total, 501 patients were included. We found no significant differences in the Kendall tau values for diagnostic measures between the groups at the 95% confidence interval (CI) level: 49% (95% CI, 43-55) for all individuals, 48% (95% CI, 40-56) for screened individuals, and 47% (95% CI, 37-56) for non-screened individuals. The overall sensitivity and specificity for all individuals in identifying high-risk tumors on CT was 65% (95% CI, 56-73) and 89% (95% CI, 85-92). The risk of ending up in the high-risk group due to overstaging among all individuals was calculated as the number needed to harm 11.7 (95% CI, 9-16). CONCLUSIONS: There is basis for improvement of CT-based preoperative staging of patients with colorectal cancer. Supplementary modalities may be needed for correct staging of patients preoperatively, especially in relation to stratification of patients into neoadjuvant treatments or tailored therapy in patients with early cancers.

Endoscopic ultrasonography and computed tomography scanning for preoperative staging of colonic cancer.

PURPOSE: With an increasing demand for more accurate preoperative staging methods for colon cancer, we aimed to compare preoperative tumour (T)- and nodal (N)-stage in patients with left-sided colon cancer by endoscopic ultrasonography (EUS) and computed tomography (CT) with post-operative histology as gold standard. METHODS: A total of 44 patients were prospectively recruited at Herlev and Roskilde University Hospitals during November 2014-January 2016. Thirty-five patients were included in the final analysis and underwent EUS, CT and surgery within 2 weeks. Diagnostic values were evaluated for "low risk" (T1+T2+T3 with ≤5 mm extramural invasion) and "high risk" (T3 with >5 mm of extramural spread + T4) colonic cancer. RESULTS: Sensitivity and specificity in "low risk" colonic cancer evaluated with EUS was 0.90 [0.74;0.98] and 0.75 [0.19;0.99] and with CT 0.96 [0.80;0.99] and 0.25 [<0.01;0.81]. EUS and CT were poor in predicting N0 or N+ disease. CONCLUSIONS: The sensitivity of EUS and CT were good and comparable regarding T-stage evaluation, while EUS had a significantly higher specificity in the evaluation of "low risk" tumours. The results obtained for "high risk" colonic cancer were difficult to evaluate due to small patient numbers. EUS could be considered as a supplement to CT scans in selecting patients for neoadjuvant therapies, or local transmural treatment, in the future. TRIAL REGISTRATION: NCT02324023.

Which is the Best Imaging Method in Pancreatic Adenocarcinoma Diagnosis and Staging - CT, MRI or EUS?

INTRODUCTION: Imaging has a decisive role in the diagnosis and staging of pancreatic cancer, the most used imaging methods being computed tomography, magnetic resonance imaging and endoscopic ultrasonography. MATERIAL AND METHOD: They were studied retrospectively over a 3 years period, 140 patients with pancreatic cancer. AIM OF THE STUDY: This study aims to determine the effectiveness of CT, MRI and EUS in diagnosis and staging of panceatic cancer. RESULTS: CT showed a diagnostic accuracy of 83.3%, with sensitivity and specificity of 81.4% and 43% respectively. MRI showed superior diagnostic accuracy compared to CT (89,1%). However, EUS demonstrated the best diagnostic value in PC (accuracy of 92,7%). Concerning the locoregional staging, the 3 diagnostic methods showed similar result. There were no significant differences concerning the diagnosis of intra-abdominal metastases. Differences have appeared in the case of extra-abdominal. Thus, there were 4 cases of lung metastases which have been identified only on CT and MRI. CONCLUSION: EUS is the most effective technique used in the diagnosis of pancreatic cancer, the present study demonstrating an accuracy of 92.7%. Moreover, EUS offers the possibility to collect samples for cytological examination by EUS guided fine needle aspiration. However, there are some limitations of EUS in identifying extra-abdominal metastases. Thus, the assessment of tumor extension must be completing by performing CT or MRI.

Interleukin-8 mRNA Expression in Locally Advanced Colorectal Cancer Patients.

PURPOSE: Interleukin-8 (IL-8) has been proven to promote progression of malignant tumours and control angiogenesis processes. We aim to determine and compare interleukin-8 (IL-8) gene expression level in colorectal tumors (CCR) and peritumoral samples obtained through endoscopic biopsy. MATERIAL AND METHODS: Total mRNA was obtained from both tumoral and peritumoral tissue samples collected from patients diagnosed with colorectal cancer. Through Quantitative Real Time PCR, IL-8 gene expression was assessed in both pathologic tissue and adjacent normal mucosa. RESULTS: In our cohort, IL8 expression was higher in adjacent normal mucosa than in tumoral tissue, in all the samples. Further studies on larger groups are required to validate our results.

EFSUMB Statement on Medical Student Education in Ultrasound [long version].

The European Federation of Societies for Ultrasound in Medicine and Biology (EFSUMB) recommends that ultrasound should be used systematically as an easy accessible and instructive educational tool in the curriculum of modern medical schools. Medical students should acquire theoretical knowledge of the modality and hands-on training should be implemented and adhere to evidence-based principles. In this paper we report EFSUMB policy statements on medical student education in ultrasound that in a short version is already published in Ultraschall in der Medizin 1.

EFSUMB Guidelines on Interventional Ultrasound (INVUS), Part V - EUS-Guided Therapeutic Interventions (short version).

The fifth section of the Guidelines on Interventional Ultrasound (INVUS) of the European Federation of Societies for Ultrasound in Medicine and Biology (EFSUMB) assesses the evidence for all the categories of endoscopic ultrasound-guided treatment reported to date. Celiac plexus neurolysis and block, vascular intervention, drainage of fluid collections, drainage of biliary and pancreatic ducts, and experimental tumor ablation techniques are discussed. For each topic, all current evidence has been extensively analyzed and summarized into major recommendations for reader consultation (short version; the long version is published online).

Advanced Endoscopic Imaging Techniques for the Study of Colonic Mucosa in Patients with Inflammatory Bowel Disease.

BACKGROUND: Crohn's disease and ulcerative colitis are inflammatory bowel diseases (IBD) associated with colorectal cancer risk in long-standing diseases. In order to assess the colonic mucosa and to discover dysplastic or neoplastic lesions, advanced endoscopic techniques are needed. Such techniques are detailed in this review: chromoendoscopy, autofluorescence imaging (AFI), narrow band imaging (NBI), i-SCAN, Fujinon Intelligent Color Enhancement (FICE) and confocal laser endomicroscopy (CLE). AIM: The aim of the review is to describe and establish the clinical impact of advanced endoscopic techniques, that could be used in IBD patients'examination in order to assess mucosal healing, microscopic inflammation, dysplasia or neoplasia. MATERIALS AND METHODS: A literature research about new endoscopic approaches of patients with IBD was made. RESULTS: A lot of studies have been performed to reveal which imaging technique might be used for IBD surveillance. Regarding dysplasia or neoplasia detection and mucosal healing or inflammation assessment, CE proved to be superior to white light endoscopy (WLE), while NBI and AFI did not show an encouraging result. I-SCAN did not improve the colonoscopy quality while FICE has been used in a few studies. CLE could be used to characterize a lesion, providing the same results as conventional histology. CONCLUSION: At the moment, CE is the only technique which has been included in guidelines for IBD surveillance. CLE can be used to assess any lesion detected with WLE during surveillance, while the other imaging techniques require.more studies to determine their efficacy or inefficacy.

EFSUMB Guidelines on Interventional Ultrasound (INVUS), Part IV - EUS-guided interventions: General Aspects and EUS-guided Sampling (Short Version).

The fourth part of the European Federation of Societies for Ultrasound in Medicine and Biology (EFSUMB) Guidelines on Interventional Ultrasound describes general aspects of endoscopic ultrasound-guided diagnostic and therapeutic interventions and assesses the evidence for endoscopic ultrasound-guided sampling. Endoscopic ultrasound combines the most advanced high-resolution ultrasound imaging of lesions within the wall and in the vicinity of the gastrointestinal tract and safe and effective fine needle-based tissue acquisition from these lesions. The guideline addresses the indications, contraindications, techniques, adverse events, training and clinical impact of EUS-guided sampling. Advantages and drawbacks are weighed in comparison with image-guided percutaneous biopsy. Based on the most current evidence, clinical practice recommendations are given for crucial preconditions and steps of EUS-guided sampling as well as for safe performance. Additionally, the guideline deals with the principles and reliability of cytopathological reporting in endoscopic ultrasound-guided sampling (short version; the long version is published online).

EFSUMB Guidelines on Interventional Ultrasound (INVUS), Part V.

The fifth section of the Guidelines on Interventional Ultrasound (INVUS) of the European Federation of Societies for Ultrasound in Medicine and Biology (EFSUMB) assesses the evidence for all the categories of endoscopic ultrasound-guided treatment reported to date. Celiac plexus neurolysis and block, vascular intervention, drainage of fluid collections, drainage of biliary and pancreatic ducts, and experimental tumor ablation techniques are discussed. For each topic, all current evidence has been extensively analyzed and summarized into major recommendations for reader consultation in clinical practice (long version).

Feasibility Study of a Novel Navigation System for Biopsy of Peripheral Lesions in the Lungs.

A novel system for electromagnetic navigation in bronchoscopy (ENB) to improve peripheral lesion targeting and diagnostic is currently under development, and preliminary tests on a complex phantom are presented in this paper. The system named Transbite is proving to be easy to use, accurate and useful for experienced and beginner users, with precision around 5-9 mm in reaching targets in sub-segmental bronchi where a conventional video-bronchoscope cannot extent. Transbite system consists of a planning and orientation software, a navigation and biopsy forceps, an active marker that is placed on patient chest and an electromagnetic tracking system from the market connected to a computer containing the software. Transbite can be used with any bronchoscopy system, has a short set-up procedure and learning curve.

Assessment of Oxidative Stress Genes SOD2 and SOD3 Polymorphisms Role in Human Colorectal Cancer.

PURPOSE: The aim of this study was to ascertain the oxidative stress genes SOD2 and SOD3 polymorphisms in patients with colorectal cancer and to assess the possible involvement of these polymorphisms that might increase the risk for patients to develop malignant intestinal tumors. MATERIAL AND METHODS: A total number of 306 subjects were divided into two groups (109 colorectal cancer patients as the study group and 197 normal healthy individuals as the control group).We genotyped two polymorphisms, SOD2 - 201A>G (rs4880) and SOD3 - 896C>G (rs1799895), by allelic discrimination, with TaqMan RT-PCR specific probes. RESULTS: No significant differences were found with either of the polymorphisms when comparing the association between them and an increased risk of developing colorectal tumors. CONCLUSION: In Romanian population, the risk of developing colorectal cancer is not increased by SOD2 and SOD3 polymorphisms.

In Vivo Experimental Study of an Endoscopic Ultrasound Multifunctional Radiofrequency Ablation Probe.

The aim of our study was to test the feasibility of a new developed RFA probe made especially for EUS use and also capable of injecting iron oxide nanoparticles within the targeted liver area. The procedures were performed on domestic pigs, divided in groups: A.liver RFA was performed; B -IONs were injected in the liver followed by EUS-RFA in the same area; C.local EUS-guided liver IONs injection were performed. After EUS measurements for the ablation areas, group A had a mean of 4.9 cm, while group B had a mean of 5.2 cm (Fig.3, 4). IONs exposure was on a median area of 3.1 cm. EUS imaging pointed out a regular oval shape in group A, and a slightly irregular outline on group B, with more echo bubbles around. MRI sections revealed different patterns for each group separately. In group A and B, RFA lesions were easily identified with specific liver parenchyma changes. Group B revealed few deposits of nanoparticles further away from the targeted point. The last group pointed out a large amount of IONs within the injection region and a larger amount of dispersed IONs within the liver than group B.