Introducing Colorectal Cancer Screening in Romania - Preliminary Results from the Regional Pilot Programs (ROCCAS).

BACKGROUND AND AIMS: Colorectal cancer (CRC) is the third cause of cancer-related death worldwide. Screening programs can reduce CRC mortality rates by up to 60%. In line with the European Union recommendations, Romania started the first four regional pilot screening programs in 2020 (the ROCCAS II projects). This study reports the interim screening performance indicators. METHODS: People aged 50 to 74 years were invited to the screening program. General practitioners (GPs) evaluated CRC risk based on a survey. High-risk or symptomatic individuals were referred directly to colonoscopy. The average risk participants received a fecal immunochemical test (FIT). Positive cases were invited to colonoscopy. Three regions were screened using the OC-SENSOR® (South-Muntenia, Bucharest-Ilfov, South-East) and one region (South-West) used the FOB GOLD®. The data was collected in the ROCCAS screening electronic registry. The following FIT parameters were evaluated: rates of return, invalidity, positivity, and colonoscopy acceptance rate according to age group, gender, region of provenience, and vulnerability status. RESULTS: We included all cases screened between January 1, 2022 and September 30, 2023. In total, 168,958 people received the FIT test within the projects. The global FIT return rate was 90%. Factors associated with a higher return rate were female gender (90.77% vs 88.83%, p<0.0001), vulnerable status (91.23% vs 88.83%; p<0.00001), and rural residence (91.84% vs 88.42%, p<0.00001). The overall positivity rate was 5.75%. It was higher in males (7.64% vs 4.57% in females, p<0.00001) and progressively increased with the age group. The total invalid FIT rate was 5.87%, significantly lower for OC-SENSOR® (2.24%) than for the FOB GOLD® (13.6%). The overall acceptability rate for colonoscopy was 51.3%. CONCLUSIONS: According to our preliminary data, GP's participation in the pilot programs ensured adequate adherence to screening through FIT. The rate for FIT return and positivity were acceptable for both tests, while the invalid rate was much higher in FOB GOLD® compared to the OC-SENSOR®. Moreover, colonoscopy acceptance needs to be improved. Our preliminary analysis revealed the screening performance indicators meet the EU recommendations and fulfill the premises for national-level expansion of the program starting in 2024.

Tissue and Circulating MicroRNA-31, MicroRNA-200b, and MicroRNA-200c Reflects Disease Activity in Crohn's Disease Patients: Results from the BIOMIR Study.

BACKGROUND AND AIMS: MicroRNAs (miR) have altered expression in multiple autoimmune disorders including inflammatory bowel disease. The aim of the study was to assess the tissue and circulating miR-31, miR-200b, and miR-200c expression levels as potential biomarkers for intestinal disease activity in patients with Crohn's disease (CD). METHODS: The study included 45 patients with histopathological confirmed CD and active disease (defined as fecal calprotectin >50 µg/g and Simple Endoscopic Score (SES) of CD >3), and 21 subjects as controls for the validation cohort. Demographic and clinical data, biomarkers (fecal calprotectin), endoscopy data, the expression levels of miR-31, miR-200b, and miR-200c in tissue and serum were assessed (by RT-PCR). Receiver operating characteristic analysis was performed to assess the miR-31, miR-200b, and miR-200c expression levels as potential biomarkers for active CD. RESULTS: Mean fecal calprotectin was 1540±890 µg/g. Mean SES-CD was 8.9±4.2. Tissue and circulating miR- 31 were significantly correlated with fecal calprotectin (r=0.81, r=0.83, p<0.01) and with SES-CD (r=0.82, r=0.79, p<0.01). The expression level of miR-31 was significantly upregulated in CD tissue cases compared to the control tissue samples (6.24±1.57 vs. 3.70±1.44; p <0.01). Similarly, serum miR-31 expression levels in CD patients were significantly upregulated compared to the control serum samples (0.78±0.42 vs. -2.07±1.00; p<0.01). The expression levels of tissue miR-200b and miR-200c were significantly upregulated in CD tissue cases compared to the control tissue samples (-5.25±0.93 vs. -4.69±0.80, p=0.03 for miR-200b, and -0.86±0.96 vs. 0.39±0.66, p<0.01 for miR-200c). Similarly, serum miR-200b and miR-200c expression levels in CD patients were significantly upregulated compared to the control serum samples (p < 0.05). Receiver operating characteristic analysis revealed that the expression levels of the selected miRNAs could help to discriminate active CD patients from healthy controls with very good specificity and sensitivity. CONCLUSIONS: Tissue and circulating miR-31, miR-200b, and miR-200c reflect disease activity in CD patients and can be used as biomarkers for active disease.

TCF7L2, CASC8, and GREM1 polymorphism and colorectal cancer in south-eastern Romanian population.

Colorectal cancer (CRC) is a heterogeneous disease with an increasing trend and with multiple epigenetic alterations and different molecular features, a major cause of mortality and morbidity. The Wnt/ß-Catenin pathway is involved in multiple aspects of cell dynamics, architecture of developing gastrointestinal tissues, and intestinal tissue homeostasis in adults, but its aberrant activity plays an important role in every aspect of colorectal carcinogenesis. The aim of our study was to investigate the association of the TCF7L2 rs7903146, CASC8 rs6983267, and Gremlin1 (GREM1) rs16969681 polymorphism in patients with CRC without other pathologies. A case-control study conducted on 31 patients diagnosed with CRC and 30 healthy controls age and sex-matched with the patients. Real time PCR was used to determine the genotypes of rs7903146, rs698267, rs1696981. We observed no association between rs6983267 and rs16969681 polymorphism and risk of CRC and low association between TCF7L2, rs7903146, polymorphism and risk of CRC. The recessive model of the TCF7L2 rs7903146 had an OR of 1.6 (95% CI 0.058-4.414, P < .05) which means that TT genotype increased the risk and possibility of development of CRC. Our study did not confirm a significant association between TCF7L2 rs7903146, CASC8 rs6983267, and GREM1 rs16969681 with CRC, but emphasizes the possibility of existence of a high risk of CRC development in patients with TT genotype of rs7903146.

The Clinicopathological Differences of Colon Cancer in Young Adults Versus Older Adults.

Purpose: Colon cancer is the third-most common and fatal cancer, with a mean age of onset >65 years. In recent years, there has been an increase in the number of cases of colon cancer in young (CCY) patients. This study investigates the biological behavior and epidemiological features of CCY and older adults in our area. Methods: Eighty-one patients (19 young adults <40 years old and 62 older adults ≥40 years old) were admitted to the General Surgery Clinic of the Constanta Emergency Hospital for colon cancer between January and December 2018. The biological behavior and epidemiological characteristics of the two groups were compared. Results: The group of young patients was characterized by finding the diagnosis on an average of 6-9 months after the onset of the first symptom, in a more advanced stage of the disease (73.69%); the onset of symptoms being nonspecific (diarrhea 26.32%, weight loss 21.05%, constipation 21.05%, and bloating 21.05%) and initially treated in a benign context, without the recommendation of additional specific explorations. The time between the onset of symptoms and the diagnosis established in the category of patients ≥40 years of age was on an average of 3-6 months, with most patients being diagnosed in the early stages of the disease (62.9%). Conclusions: Improving health education through colon cancer information programs should be implemented with information on alert symptoms and indications on the steps that a symptomatic patient should follow and no longer ignore his or her symptoms, because health is not necessarily the prerogative of youth.

KRAS, NRAS, BRAF, PIK3CA, and AKT1 signatures in colorectal cancer patients in south-eastern Romania.

Somatic mutations in the oncogenes of the epidermal growth factor receptor signaling pathway play vital roles in colorectal carcinogenesis and have been closely linked with clinical resistance to monoclonal therapy. In this study, we have analyzed the mutation frequencies of 5 genes and compared the genetic findings with clinicopathological variables in order to determine diagnostically relevant alterations and compare these findings with those of other studies In our Sanger sequencings, KRAS (exons 2, 3, and 4), NRAS (exons 2, 3, and 4), PIK3CA (exons 9 and 20), BRAF (exon 15), AKT1 (exon 2) genes, and microsatellite instability (MSI) status were analyzed using an ABI 3500 analyzer in a cohort of 58 Romanian colorectal cancer (CRC) patients who underwent surgical resection at Emergency County Clinical Hospital in Constanța, Romania. In our series, mutation rates of KRAS, BRAF, PIK3CA, and AKT1 genes were 39.63%, 8.62%, 6.88%, and 3.44%, respectively. By contrast, we did not find any tumor harboring mutation in the NRAS gene. Notably, the KRAS and PIK3CA mutations were not mutually exclusive, 1 patient harbored 2 mutations in exon2, codon 12 (Gly12Val) of KRAS and exon 20, codon 1047 (His1047Arg) of PIK3CA. The finding of our study are generally consistent with data found in the literature. Regarding to clinicopathological variables, mutation of KRAS was associated with distant metastasis at the time of diagnosis, while mutation of BRAF was significantly associated with MSI-H in contrast with MSI-L/MSS tumors. Moreover, PIK3CA mutation tends to be located in the proximal segment of the colon and to be well/moderately differentiated compared to wild-type tumors. In conclusion, the assessment of these mutations suggests that CRC patients from southeast Romania exhibit a mutation profile similar to other populations. These results could contribute to creating a better method of qualifying patients for molecularly targeted therapies and obtaining better screening strategies.

Influence of type II diabetes mellitus on postoperative complications following colorectal cancer surgery.

Diabetes mellitus (DM) promotes colorectal cancer (CRC) carcinogenesis through complex processes and is considered as an independent risk factor for cancer in general and for CRC in particular. Diabetic patients have complications in the postoperative period following CRC surgery. The aim of the present study was to explore the effect of type II DM (T2DM) on postoperative outcomes for CRC compared with non-diabetic patients. The present study analyzed the data from patients admitted to the General Surgery Department, Emergency Hospital of Constanța (Romania) diagnosed with CRC and DM compared with a control group (patients with CRC, without DM, recruited in the same period and frequency matched to cases by number, sex and age) analyzing patient comorbidities and postoperative complications. A total of 61 patients had undergone surgery for CRC and met the inclusion criteria in the present study conducted during September 2020-2021. A total of 30 patients associated T2DM. Diabetic patients have been associated with more comorbidities than non-diabetics; the age-adjusted Charlson comorbidity index score ≥6 was identified in 90% of diabetic patients compared with 45.2% of controls. Grade III Clavien-Dindo classification was observed in 13.3% diabetic patients compared with 3.2% of non-diabetic patients. Additionally, a higher rate of urinary and pulmonary complications (6.7 vs. 3.2% in controls respectively) in patients with diabetes was found. Postoperative hospitalization was prolonged in diabetic patients (P=0.042). Univariate and multivariate analyses revealed that the laparoscopic approach for diabetic patients was found to be associated with

Design, Characterization, and Anticancer and Antimicrobial Activities of Mucoadhesive Oral Patches Loaded with Usnea barbata (L.) F. H. Wigg Ethanol Extract F-UBE-HPMC.

The oral cavity's common pathologies are tooth decay, periodontal disease, and oral cancer; oral squamous cell carcinoma (OSCC) is the most frequent oral malignancy, with a high mortality rate. Our study aims to formulate, develop, characterize, and pharmacologically investigate the oral mucoadhesive patches (F-UBE-HPMC) loaded with Usnea barbata (L.) F.H. Wigg dry ethanol extract (UBE), using HPMC K100 as a film-forming polymer. Each patch contains 312 µg UBE, with a total phenolic content (TPC) of 178.849 µg and 33.924 µg usnic acid. Scanning electron microscopy (SEM) and atomic force microscopy (AFM) were performed for their morphological characterization, followed by Fourier transform infrared spectroscopy (FTIR), X-ray diffraction (XRD), and thermogravimetric analysis (TGA). Pharmacotechnical evaluation involved the measurement of the specific parameters for mucoadhesive oral patches as follows: weight uniformity, thickness, folding endurance, tensile strength, elongation, moisture content, pH, disintegration time, swelling rate, and ex vivo mucoadhesion time. Thus, each F-UBE-HPMC has 104 ± 4.31 mg, a pH = 7.05 ± 0.04, a disintegration time of 130 ± 4.14 s, a swelling ratio of 272 ± 6.31% after 6 h, and a mucoadhesion time of 102 ± 3.22 min. Then, F-UBE-HPMCs pharmacological effects were investigated using brine shrimp lethality assay (BSL assay) as a cytotoxicity prescreening test, followed by complex flow cytometry analyses on blood cell cultures and oral epithelial squamous cell carcinoma CLS-354 cell line. The results revealed significant anticancer effects by considerably increasing oxidative stress and blocking DNA synthesis in CLS-354 cancer cells. The antimicrobial potential against Staphylococcus aureus ATCC 25923, Pseudomonas aeruginosa ATCC 27353, Candida albicans ATCC 10231, and Candida parapsilosis ATCC 22019 was assessed by a Resazurin-based 96-well plate microdilution method. The patches moderately inhibited both bacteria strains growing and displayed a significant antifungal effect, higher on C. albicans than on C. parapsilosis. All these properties lead to considering F-UBE-HPMC suitable for oral disease prevention and therapy.

Association of TCF7L2, CASC8 and GREM1 Polymorphisms in Patients with Colorectal Cancer and Type II Diabetes Mellitus.

BACKGROUND: The aim of the study is to explore the association between the TCF7L2 rs7903146, CASC8 rs6983267 and GREM1 rs16969681 polymorphisms in patients diagnosed with type 2 diabetes mellitus (T2DM) and colorectal cancer. METHODS: Sixty individuals were enrolled in this case-control study: thirty with colorectal cancer and type II diabetes mellitus (T2DM) and thirty healthy control individuals. Real-time PCR was used to determine the genotypes of TCF7L2 rs7903146, CASC8 rs 6983267 and GREM1 rs16969681 in patients with CRC and T2DM and in patients without T2DM and CRC. The Hardy-Weinberg equilibrium was determined in the control group for the genotype distribution of every polymorphism. RESULTS: People carrying the TT genotype of rs7903146, rs6983267 and rs1696981 had a significant association with T2DM and CRC. Moreover, the people with the TT genotype of rs1696981 had a greater risk for T2DM and CRC (OR = 7, CI 0.397-23.347). CONCLUSIONS: TCF7L2 rs7903146, CASC8 rs6983267 and GREM1 rs16969681 could be risk factors for the association of T2DM with CRC.

Extended Lymphadenectomy for Proximal Transverse Colon Cancer: Is There a Place for Standardization?

Background and Objectives: Complete mesocolon excision and high vascular ligation have become a standard procedure in the treatment of colon cancer. The transverse colon has certain embryological and anatomical particularities which require special attention in case of oncological surgeries. Proximal transverse colon cancer (TCC) can metastasize to the lymph nodes in the gastrocolic ligament. The aim of this study is to assess the tumor involvement of these lymph nodes and to determine the applicability of gastrocolic ligament lymph nodes dissection as the standard approach for proximal transverse colon cancer. Materials and Methods: this study analyzes the cases of patients admitted to the Surgery Department, diagnosed with proximal transverse colon cancer, with tumor invasion ≥ T2 and for which complete mesocolon excision with high vascular ligation and lymphadenectomy of the gastrocolic ligament (No. 204, 206, 214v) were performed. Results: A total of 43 cases operated during 2015−2020 were included in the study. The median total number of retrieved central lymph nodes was 23 (range, 12−38), that had tumor involvement in 22 cases (51.2%). Gastrocolic ligament tumor involvement was found in 5 cases (11.6%). The median operation time was 180 min, while the median blood loss was 115 mL (range 0−210). The median time of hospitalization was 6 days (range, 5−11). Grade IIIA in the Clavien-Dindo classification was noticed in 3 patients, with no mortality. Upon Kaplan−Meier analysis, tumors > T3 (p < 0.016) and lymph node ratio < 0.05 (p < 0.025) were statistically significant. Conclusions: lymph node dissection of the gastrocolic ligament in patients with advanced proximal transverse colon cancer may improve the oncological outcome in T3/T4 tumors, and therefore standardization could be feasible

Risk Factors for Extraintestinal Manifestations in Inflammatory Bowel Diseases - Data from the Romanian National Registry.

BACKGROUND AND AIMS: Identifying the risk factors for extraintestinal manifestations (EIMs) in inflammatory bowel diseases (IBD) may optimize the therapeutic decision. We aimed to assess the prevalence of EIMs in IBD patients in Romania and to determine the risk factors. METHODS: We analyzed 2,626 patients registered in the Romanian IBD Prospect National Registry. We performed a descriptive cross-sectional study to assess the point prevalence of EIMs, calculating global prevalence and analyzing the different types of EIMs and their respective frequencies were carried out. Demographic and clinical risk factors were researched as possible predictors for EIMs development, based on the results of the univariate and multivariate logistic regression analysis. RESULTS: The overall point prevalence of EIMs was 16.3%. A significantly higher frequency of EIMs in Crohn's disease (CD) was noted in comparison to ulcerative colitis (UC) and IBD unclassified (IBDU) (23.2% vs 11.3% and 16.3%, respectively, p<0.001). The most frequent type of EIM was peripheral arthropathy (8.3%), significantly associated with CD (p<0.001). Univariate analysis highlighted the significant independent common predictive risk factors for EIMs, in both CD and UC patients: female gender, patient's urban area of origin, anemia, hypoalbuminemia, and high level of C-reactive protein (CRP), while significant independent IBD phenotype-related risk factors were ileocolonic location and concomitant involvement of upper gastrointestinal tract for CD, non-smoker status and both moderate and severe disease activity for UC (p<0.05). Multivariate analysis determined that female CD patients with moderate or severe disease activity, with other than isolated ileal disease, and female UC patients with moderate or severe extensive colitis are the most likely to develop EIMs. CONCLUSIONS: IBD patients are experiencing EIMs in a large proportion, with higher rates for CD. As EIMs negatively affect patient outcomes, foreseeing the risk by identifying independent and associated predictive factors could be a first step to optimal work-up and treatment.

A plea for a unified approach to sedation in gastrointestinal endoscopy in Romania: results from a prospective multicentric trial.

Background. Adequate sedation is a prerequisite for quality endoscopic examination of the digestive tract. We aimed to evaluate the current practices and safety profile of sedation for gastrointestinal endoscopy in Romania and its impact on the technical success of the procedure and procedure-related adverse events. Methods. We conducted a prospective, multicentric, observational study including all patients undergoing digestive endoscopic procedures under various degrees of sedation. We collected data regarding the endoscopic procedure, type and degree of sedation, drug regimens, personnel in charge of sedation, and relevant patient related information. The main study outcome was the rate of sedation-related adverse events; secondary study outcomes included procedure-related adverse events and the impact of sedation on procedure success. Results. 1,043 consecutive endoscopic procedures from eight Romanian endoscopy units were included in our study. Sedation regimens were highly variable between participating centers, with 566 (54%) of procedures being performed under sedation provided by an anaesthesiologist. Sedation-related adverse events occurred in 40 cases (3.8%), most of them were mild respiratory and cardiovascular events and all reversed spontaneously. On multivariate analysis, male gender, procedure type (endoscopic ultrasound and endoscopic retrograde cholangiopancreatography) and deep sedation were risk factors for complications. The endoscopy unit, ASA status, age and type of sedative did not influence the complication rate. Conclusion. In conclusion, sedation for endoscopic procedures is generally safe, despite a high variability in sedation practices between centers in Romania. Establishing a national guideline on sedation for gastrointestinal endoscopy will ensure consistent and safe practice for these procedures.

Does rifaximin offer any promise in Crohn's disease in remission and concurrent irritable bowel syndrome-like symptoms?

ABSTRACT: Microbiota plays an important role in many diseases including inflammatory bowel diseases. Inflammatory bowel disease patients can have concurrent irritable bowel syndrome symptoms similar to those associated with a flare. The potential role of gut dysbiosis in the pathogenesis of inflammatory bowel disease provides a rationale for treating such patients with rifaximin. This study aimed to assess the efficacy of rifaximin in the management of irritable bowel syndrome-like symptoms (bloating, abdominal pain, stool consistency) and quality of life in patients with Crohn's disease in remission.The present study included 86 patients with Crohn's disease in remission (fecal calprotectin <50 µg/g, C-reactive protein <0.5 mg/dL, simple endoscopic score for Crohn's disease <2) and associated irritable bowel syndrome-like symptoms (bloating, abdominal pain, diarrhea). These patients were randomly assigned to rifaximin treatment group (44 patients) and the control group (42 patients). Besides the baseline inflammatory bowel disease treatment and antispasmodics (as needed), patients in the rifaximin treatment group received 3 repeated courses of treatment, each course being represented by 1200 mg/d of rifaximin for 10 days and 20 days free of treatment (3 months consecutively); patients in the control group also received antispamodics as needed and were observed for 3 months.Monthly analyses of bloating score, abdominal pain score, stool consistency score, and quality of life score showed significant improvement after treatment in the rifaximin group in contrast with control group. Significantly more patients in the rifaximin group than in the control group met the criteria for adequate improvement of bloating score after 3 months of treatment (59.09% vs 19.04%, P = .01), adequate improvement of abdominal pain score (54.5% vs 21.4%, P = .04), stool consistency score (34.09% vs 14.2%, P = .03), and quality of life score (70.4% vs 21.4%, P < .001).Rifaximin in a dose of 1200 mg/d, 10 d/mo, 3 months consecutively is an effective medication for concurrent irritable bowel syndrome-like symptoms in patients with Crohn's disease in remission.

Molecular profiling of the colon cancer in South-Eastern Romania: Results from the MERCUR study.

ABSTRACT: Colorectal cancer is a heterogeneous disease with multiple epigenetic alterations and different molecular features. The molecular classification is based on 2 major distinct pathways: microsatellite stable pathway and the microsatellite instability pathway. Molecular profiling of colorectal cancer provides important information regarding treatment and prognosis. Aim of the study was to assess the frequency of microsatellite instability in colon cancer and the clinicopathological characteristics of the tumors with high level of microsatellite instability (MSI-H) in our region. The secondary outcome was to assess the frequency of v-raf murine sarcoma viral oncogene homolog B1 (BRAF) mutations in colon cancer.The study included 129 patients with colon cancer fit for surgery. Demographic data, clinical and pathological data, immunohistochemistry staining pattern (4 mismatch repair proteins were investigated), and BRAF gene mutations were assessed. According to microsatellite instability status by polymerase chain reaction, patients were divided into 3 groups: microsatellite stable (MSS) = 108 patients, high level of microsatellite instability (MSI-H) = 15 patients and low level of microsatellite instability (MSI-L) = 6 patients. Different clinicopathological comparisons between MSS and MSI-H patients, and between MSS and MSI-L patients were performed.Microsatellite instability was found in 16.3% patients: 11.6% had MSI-H and 4.7% had MSI-L. Significantly more patients in the MSI-H group than in the MSS group were female (P = .01) and had a family history of colon cancer (P < .001). MSI-H and MSI-L groups were associated with the ascending colon location of the tumors, were mostly type G3, T2, and stage I whereas MSS tumors were mostly G2, pT3, and stage III. Overall, BRAF mutations were identified in 18/129 patients (13.9%). BRAF mutant tumors were predominantly associated with MSI-H and MSI-L tumors. Immunohistochemistry had a sensitivity of 76% and a specificity of 89% in detecting MSI tumors and an accuracy of 87.6%.The frequency of microsatellite instability in our study was 16.3%. MSI-H is a distinct molecular phenotype of colon cancer with particular features: female gender, family history of colorectal cancer, a predilection for the ascending colon, poorly differentiated, predominantly T2, and stage I. The frequency of BRAF mutations was 13.9% and mutations were more often present in the MSI tumors.

The diagnostic value of miR-92a, -143, and -145 expression levels in patients with colorectal adenocarcinoma from Romania.

MicroRNAs (miRNAs) refers to a small, short non-coding RNA of endogenous class. They have shown to have an increasingly altered expression in many types of cancer, including colorectal cancer (CRC).In the present study, miRNA TaqManMGB and qRT-PCR was used to quantify the expression and clinical significance of 3 mature human miRNA in 82 pairs of colorectal adenocarcinoma tissues and normal adjacent tissue samples (NATS) collected from patients of the south-east part of Romania. Differences between CRC and NATS were analyzed using Wilcoxon test, while correlations between miRNAs expression levels and clinicopathological features were examined using non-parametric tests. In addition, the ability of selected miRNAs to function as biomarkers and, as potential indicators in CRC prognosis was also examined.When the miRNA expression was compared in CRC related NATS, miR-143, and miR-145 were significantly underexpressed (4.99 ±â€Š-1.02 vs -5.66 ±â€Š-1.66, P < .001; -4.85 ±â€Š-0.59 vs -9.27 ±â€Š-1.51, P < .001, respectively), while the pattern of miR-92a was significantly overexpressed (-5.55 ±â€Š-2.83 vs -4.92 ±â€Š-2.44, P < .001). Moreover, the expression levels of selected miRNAs were identified to be correlated with gradual increases in fold change expression with the depth of tumor invasion, lymph node invasion, and maximal increases with distant metastasis. Furthermore, the receiver operating characteristic analysis demonstrated that potential diagnostic of miR-143, miR-145, and miR-92a in discriminating CRC from NATS, with the area under the curve of 0.74, 0.85, and 0.84 respectively. The Kaplan-Meier and the log-rank test showed that a high level of miR-92a and low levels of miR-143 and miR-145 predicted poor survival rate in our cohorts.In conclusion, we can summarize that miR-145 and miR-143 are decreased, while miR-92 is increased in CRC compared to NATS, and associated with different stages of CRC pathogenesis. Thus, the expression of selected miRNAs can represent potential diagnostic and prognostic tools in patients with CRC from Romania.

SRED-ARCE Recommendations for Minimally Invasive Interventions During the COVID-19 Pandemic in Romania.

The Romanian Society of Digestive Endoscopy (SRED) and the Romanian Association of Endoscopic Surgery (ARCE) have decided to establish a joint working group to elaborate specific recommendations for organizing the diagnostic and the minimally invasive interventional procedures, in the context of the COVID-19 pandemic. The recommendations are based on the guidelines of the international societies of endoscopy and gastroenterology (ESGE / BSG / ASGE / ACG / AGA), respectively endoscopic surgery (EAES SAGES) (4-8), on the experience of countries severely affected by the pandemic (Italy, France, Spain, USA, Germany, etc.) and they will be applied within the limits of measures imposed at local and governmental level by the competent authorities. On the other hand, these recommendations should have a dynamic evolution, depending on the upward or downward trend of the COVID-19 pandemic at regional and local level, but also according to the findings of professional and academic societies, requiring regular reviews based on the publica tion of further recommendations or international clinical trials. The objectives of the SRED and ARCE recommendations target the endoscopic and laparoscopic surgery activities, to support their non discriminatory used for diagnostic or therapeutic purposes, pursuing the demonstrated benefits of these procedures, in safe conditions for patients and medical staff.

Genetic Antibiotic Resistance of Helicobacter pylori in South-Eastern Romania.

BACKGROUND AND AIM: Helicobacter pylori infection is very common worldwide, and it is associated with an important gastric pathology. Treatment of this infection is difficult and consists of the combination of two or three antibiotics. However, the rate of resistance to treatment is high. Antimicrobial resistance of Helicobacter pylori is based on its cultivation in the laboratory and testing of phenotypic susceptibility, a time-consuming, laborious method. This study aimed to detect the genetic resistance to antibiotics of Helicobacter pylori in the south-eastern region of Romania. METHODS: Ninety patients with positive rapid urease test gastric biopsy samples were tested. Genetic resistance to antibiotics (fluoroquinolone and clarithromycin) was tested by GenoType HelicoDR kit (Hain Lifescience GmbH, Germany). RESULTS: Clarithromycin resistance mutations were detected in 20% of patients, the commonest mutation in our study beeing A2147G (associated with high level of clarithromycin resistance and lower cure rates). Fluoroquinolones resistance mutations were detected in 30% of patients, and the most common mutations were D91N, D91G, and N87K. There was no correlation with patients gender or age, with the exception of fluoroquinolone resistance, which was detected more frequently in females.   Conclusions. Clarithromycin and fluoroquinolone resistance of Helicobacter pylori is moderately high in our study. There is a need for monitoring Helicobacter resistance patterns in Romania to provide data that can guide empirical treatment. This is the first published study on the genetic resistance of Helicobacter pylori in Romania.

Triple Antioxidant Therapy, an Alternative for Patients with Chronic Liver Disease - A Prospective Multicenter Interventional Study.

Background: Non-alcoholic fatty liver disease (NAFLD) has increased exponentially in recent years in Western European countries, where the number of hepatitis of viral etiology has been declining, and it is thought to be the most common cause of chronic liver disease in the near future (1). Currently, NAFLD is both the second most common cause of hepatocellular carcinoma (HCC) and the second most common indication for liver transplantation (2-4). This problem is very serious, as cases of NAFLDs are increasingly in children, a population with a long life ahead, and in whom the disease has all the time to progress to cirrhosis and HCC (5, 6). Objectives: The goal of this prospective study is to determine the effect of an original formula consisting in silymarin, organic selenium and alpha lipoic acid, in reducing liver damage in patients with chronic liver disease. Material and methods: The study started in March 2018, initially with a group of patients from Bucharest, integrated in the study at St. Mary's Hospital. In October 2018 it was expanded at the national level to 1 718 patients, monitored by 145 investigating physicians from 134 centers, with an average of 11.8 patients per investigating physician. Outcomes: Taking each stage of fatty liver disease (FLD) at T0 moment (the beginning of the study), we observed that 25% of patients with grade I FLD had no sign of disease at the end of the study, 74% of those with grade II FLD recovered or improved their health, and 83% of patients with grade III FLD recovered or improved their health. There were 149 patients with no FLD detected at the end of the study (recovered). Conclusion: Based on triple antioxidant therapy, the original formula improved the evolution and prognosis of patients with chronic liver disease.

Percutaneous Endoscopic Gastrostomy with Jejunal Extension Tube for the Delivery of Levodopa Carbidopa Intestinal Gel: Clinical Practice Guidelines of the Romanian Society of Digestive Endoscopy.

Percutaneous endoscopic gastrostomy with jejunal extension (PEG/J) was first described in 1998 and has become the standard technique for fixing the tube in place for levodopa carbidopa intestinal gel (LCIG) infusion. The Romanian Society of Digestive Endoscopy (RSDE) decided to create a consensus paper to meet the needs in medical training and practice. After reviewing the available published data and existing recommendations, a consensus process was carried out involving the leaders of opinion in this field. The resulting text and recommendations were approved, after reaching expert consensus, and reflects the views of the RSDE for the best practice of PEG/J tube placement. The pull through method ("pull technique") is the prevailing PEG-tube placement procedure in Romania. The procedure can be performed with intravenous sedation combined with local anesthesia. Although minor complications are common, serious complications are infrequent, and the tube insertion procedures have a good safety record. Redo procedures are sometimes necessary and clinicians should be aware of these situations.

Gastrointestinal endoscopy in patients on direct oral anticoagulants. A consensus paper of the Romanian Society of Gastroenterology and Hepatology.

Management of patients undergoing endoscopy and under treatment with the newer direct oral anticoagulants (DOACs) is a common and a complex clinical issue that gastroenterologists have to face more and more often these days. The increasing use of DOACs in patients requiring both short- and long-term anticoagulation is mostly due to the advantages these agents offer, among which the lack of monitoring requirements and the reduced need of dose adjustments are perhaps the most important ones. Managing these patients in the peri-endoscopic period implies balancing the risk for thrombosis that a certain patient carries and the bleeding risk associated with the endoscopic procedure itself. The Romanian Society of Gastroenterology and Hepatology decided to create a consensus paper to serve to practitioners and teachers. After reviewing the available published data and existing recommendations, a Delphi consensus process was carried out involving the leaders of opinion in this field. After reaching expert consensus, we provide herein guidance for a practical approach of DOACs therapy management in patients with endoscopic interventions.