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Venous thromboembolic events (VTE) are common in patients with colorectal cancer (CRC) and represent a significant contributor to morbidity and mortality. Risk stratification is paramount in deciding the initiation of thromboprophylaxis and is calculated using scores that include tumor location, laboratory values, patient clinical characteristics, and tumor burden. Commonly used risk scores do not include the presence of molecular aberrations as a variable. This retrospective study aims to confirm the link between KRAS-activating mutations and the development of VTE in CRC. A total of 166 patients were included in this study. They were split into two cohorts based on KRAS mutational status. We evaluated the frequency and mean time to VTE development stratified by the presence of KRAS mutations. Patients with mutant KRAS had an odds ratio (OR) of 2.758 for VTE compared to KRAS wild-type patients, with an increased risk of thrombosis being maintained in KRAS mutant patients even after adjusting for other known VTE risk factors. Taking into account the results of this study, KRAS mutation represents an independent risk factor for VTE. [ABSTRACT FROM AUTHOR]

The Golgi apparatus plays a central role in protein sorting, modification and trafficking within cells; its dysregulation has been implicated in various cancers including those affecting the GI tract. This review highlights two Golgi target proteins, namely GOLPH3 and GOLGA proteins, from this apparatus as they relate to gastroenterological cancers. GOLPH3—a highly conserved protein of the trans-Golgi network—has become a key player in cancer biology. Abnormal expression of GOLPH3 has been detected in various gastrointestinal cancers including gastric, colorectal and pancreatic cancers. GOLPH3 promotes tumor cell proliferation, survival, migration and invasion via various mechanisms including activating the PI3K/Akt/mTOR signaling pathway as well as altering Golgi morphology and vesicular trafficking. GOLGA family proteins such as GOLGA1 (golgin-97) and GOLGA7 (golgin-84) have also been implicated in gastroenterological cancers. GOLGA1 plays an essential role in protein trafficking within the Golgi apparatus and has been associated with poor patient survival rates and increased invasiveness; GOLGA7 maintains Golgi structure while having been shown to affect protein glycosylation processes. GOLPH3 and GOLGA proteins play a pivotal role in gastroenterological cancer, helping researchers unlock molecular mechanisms and identify therapeutic targets. Their dysregulation affects various cellular processes including signal transduction, vesicular trafficking and protein glycosylation, all contributing to tumor aggressiveness and progression. [ABSTRACT FROM AUTHOR]

The identification of obvious, large, suggestive lesions no longer poses a challenge to endoscopist, especially since early stage cure requires the diagnosis of neoplastic lesions in early neoplastic stages or in situ neoplasia. Thus, new techniques have been developed to highlight the characteristics of the mucosa that do not show obvious lesions on ordinary endoscopy. Beginning with magnification endoscopy, aided by coloring techniques (initially with contrast agents and then virtual chromoendoscopy), technology has advanced to the development of techniques based on tissue fluorescence and autofluorescence, endocytoscopy, optic coherence tomography, confocal laser endomicroscopy, biomolecular endoscopy. The concept of optical biopsy includes all the methods by which cell surface and subepithelial tissue can be evaluated, providing in vivo and in situ diagnosis, with the possibility of real-time diagnosis, which were so far possible only ex vivo, by biopsy and histological or cytologic examination. [ABSTRACT FROM AUTHOR]

Pancreatic cysts are a heterogeneous group of lesions, being categorized, in general, into non-neoplastic (for example pseudocysts) and neoplastic cystic lesions. They are usually identified incidentally, when abdominal imaging is performed for some other indication. Although most of the pancreatic cysts are benign, considering its potential of malignancy, patients should be submitted to a rigorous evaluation protocol. High-resolution computed tomography or resonance imaging /magnetic resonance cholangiopancreatography allows a characterisation of the lesion and may provide a presumptive diagnosis if characteristic features are present. Patients with more than one high-risk feature for malignancy on cross-sectional imaging should undergo endoscopic ultrasonography and endoscopic ultrasonographic guided fine needle aspiration, with characterization of the contents of the cystic fluid. Another essential aspect is selecting the cases that should be referred for pancreatic surgery, which is encumbered with substantial morbidity and mortality, particularly in the aging population and, therefore, should be restricted to the cases that are expected to benefit the most of it. This review discusses the challenges the clinician faces in evaluating pancreatic cysts, and the evidence-based medical decision of such cases in the light of existing data. [ABSTRACT FROM AUTHOR]

Background: In patients with chronic hepatitis C (CHC), obesity is involved in the pathogenesis of insulin resistance, fatty liver disease and progression of fibrosis. The objective of this study was to compare a normoglucidic low-calorie diet (NGLCD) with a low-fat diet (LFD) among participants with CHC. Aimed to measure the impact of dietary changes in reduction of insulin resistance, obesity but also in steatosis and fibrosis. Methods: Randomized, controlled trial in three medical centers with assessments at baseline, 6 months and 12 months. Participants were patients over 35 years with chronic hepatitis C (n = 120) with BMI over 25 kg/m2 We evaluated the effects of NGLCD vs. LFD in weight management and metabolic improvement. The primary endpoint was to measure the impact of dietary changes through nutritional intervention in reversibility of insulin resistance, obesity, steatosis, and fibrosis. We performed anthropometric measurements, fasting glucose profile, serum lipids, liver profile, blood count at baseline, 6 and 12 months. Steatosis was evaluated using ultrasonographic criteria. Liver fibrosis was non-invasively assessed. Results: After 6 and 12 months of intervention, both groups had a significant decrease in caloric consumption. At 6 months, weight loss was greater in the NGLCD group (-5.02 ± 3.43 kg vs. -4.1 ± 2.6 kg; p = 0.002) compared to the LFD group. At 1 -year, however, weight loss was similar in both groups (-3.9 ± 3.3 kg vs. -3.1 ± 2.6 kg; p = 0.139). At 12 months, fasting plasma glucose, fasting plasma insulin, and HOMA-IR had significant improvements in both groups. With both diets aspartate aminotransferase (AST), alanine aminotransferase (ALT), gamma-glutamyl transpeptidase (GGT) decreased with significant differences; also there were significant improvements in AST/ALT ratio, Forns fibrosis index. The two diets were associated with reduction of both the prevalence and the severity of steatosis (all p < 0.001). At 12 months, total cholesterol, HDL-cholesterol, triglycerides improved in both groups (all p < 0.05). Conclusions: The present study establishes the benefits of low-calorie diet and low-fat diet in management of patients with hepatitis C regarding improvement of insulin resistance, steatosis and also fibrosis. Overweight or obese patients with CHC undergoing a lifestyle intervention (specific dietary intervention and physical activity) for 1-year had significant improvements in body weight, lipid and hepatic profile. [ABSTRACT FROM AUTHOR]

Background: Coeliac disease (CD), due to its protean clinical manifestation, is still very under diagnosed in adults and delays in diagnosis may take years and even decades. Simple tools to find cases in primary care may help to identify patients for further diagnostic tests. We have evaluated the usefulness of an on site rapid fingertip whole blood point-of-care test (POCT) for such a purpose. Methods: As CD is known to run within families, we tested 148 healthy relatives of 70 Romanian index cases with biopsy-proven CD (87% of all first-degree family members, median age 36 years) for the presence of circulating autoantibodies. In addition to performing the POCT (which measures blood erythrocyte self-TG2-autoantibody complexes) on site, blood was drawn for later evaluations of serum IgA-class endomysial antibodies (EMA). EMA-positive sera were further tested for transglutaminase 2 antibodies (TG2-IgA). All serological parameters were analyzed blindly in a centralized laboratory that had no knowledge of the on site POCT result. Endoscopic small intestinal biopsies was recommended for all POCT- or EMA-test positive subjects. Results: In on site testing the POCT was positive in 12/148 first-degree relatives (8%) and all these subjects were also serum EMA-positive. A positive EMA test was found only in one other subject. All remaining 135 healthy first-degree relatives were negative for both POCT and EMA. Four subjects positive for both POCT and EMA were negative for TG2-IgA. Ten out of thirteen of the antibody-positive subjects agreed to undergo endoscopy. The POCT was found to be positive in 8/9 first-degree relatives having coeliac-type mucosal lesions of grade Marsh 2 (n = 3) or Marsh 3 (n = 6). The three POCT-positive subjects not agreeing to undergo endoscopy were also both EMA- and TG2-IgA-positive. Conclusion: The fingertip whole blood rapid POCT might fulfill the unmet need for a simple and cheap case-finding biomarker for early detection and presumptive diagnosis of CD. Confirmatory studies are warranted in adult case-finding in specialized outpatient clinics and in primary care. [ABSTRACT FROM AUTHOR]

Abstract: Portopulmonary hypertension is a form of pulmonary arterial hypertension that has gained interest in recent years with the development of liver transplantation techniques and new pulmonary vasodilator therapies. Portopulmonary hypertension is defined as pulmonary artery hypertension associated with portal hypertension with or without advanced hepatic disease. Echocardiography plays a major role in screening for portopulmonary hypertension but right heart catheterization remains the gold standard for diagnosis. The treatment of patients with portopulmonary hypertension consists of general measures that apply to all patients that carry the diagnosis of pulmonary hypertension and specific vasodilator therapies. These new therapies showed encouraging results in patients who would otherwise have a contraindication for liver transplantation. The review presents a summary of the current knowledge on the epidemiology, diagnosis, treatment and prognosis of patients with portopulmonary hypertension. [Copyright &y& Elsevier]

Pancreatic cystic lesions (PCL) are frequently encountered in clinical practice and some are referred to surgery due to their neoplastic risk or malignant transformation. The management of PCL involves complex decision-making, with postoperative surveillance being a key component for long-term outcomes, due to the potential for recurrence and postoperative morbidity. Unfortunately, the follow-up of resected patients is far from being optimal and there is a lack of consensus on recommendations with regard to timing and methods of surveillance. Here, we summarize the current knowledge on the postoperative surveillance of neoplastic pancreatic cysts, focusing on the mechanisms and risk factors for recurrence, the recurrence rates according to the initial indication for surgery, the final result of the surgical specimen and neoplastic risk in the remaining pancreas, as well as the postsurgical morbidity comprising pancreatic exocrine insufficiency, metabolic dysfunction and diabetes after resection, according to the type of surgery performed. We analyze postsurgical recurrence rates and morbidity profiles, as influenced by different surgical techniques, to better delineate at-risk patients, and highlight the need for tailored surveillance strategies adapted to preoperative and operative factors with an impact on outcomes. [ABSTRACT FROM AUTHOR]

Non-alcoholic fatty liver disease (NAFLD) is the predominant cause of chronic liver conditions, and its progression is marked by evolution to non-alcoholic steatosis, steatohepatitis, cirrhosis related to non-alcoholic steatohepatitis, and the potential occurrence of hepatocellular carcinoma. In our systematic review, we searched two databases, Medline (via Pubmed Central) and Scopus, from inception to 5 February 2024, and included 73 types of research (nine clinical studies and 64 pre-clinical studies) from 2854 published papers. Our extensive research highlights the impact of Berberine on NAFLD pathophysiology mechanisms, such as Adenosine Monophosphate-Activated Protein Kinase (AMPK), gut dysbiosis, peroxisome proliferator-activated receptor (PPAR), Sirtuins, and inflammasome. Studies involving human subjects showed a measurable reduction of liver fat in addition to improved profiles of serum lipids and hepatic enzymes. While current drugs for NAFLD treatment are either scarce or still in development or launch phases, Berberine presents a promising profile. However, improvements in its formulation are necessary to enhance the bioavailability of this natural substance. [ABSTRACT FROM AUTHOR]

Background & 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. [ABSTRACT FROM AUTHOR]

Background & Aims: Real-world assessments of efficacy and safety of advanced therapies used for inflammatory bowel disease (IBD) patients are limited. We aimed to report safety, efficacy and treatment persistence of new molecules (infliximab, adalimumab, vedolizumab, tofacitinib, ustekinumab) in a retrospective multicentric national Romanian analysis. Methods: We conducted a nationwide, retrospective observational multicentric study. Data were collected retrospectively from electronic and paper files. Patients who started on one of the five investigated molecules during December 2019-December 2021 were included. The main outcome measures were clinical remission, endoscopic healing, persistence on treatment and safety data. Results: A total of 678 adult patients from 24 Romanian IBD centers with a diagnosis of ulcerative colitis or Crohn's disease were included. Participants had previously failure to one (268, 39.5%), two (108, 15%) or more treatment lines and only 38% (259) were biologic naïve. In the 24 months study period, most patients were started on vedolizumab (192, 28%), followed by adalimumab, infliximab, ustekinumab and tofacitinib. In biologic-naïve patients, most physicians (72%) preferred anti-TNF treatment as first line biologic (93 patients started on infliximab, 92 on adalimumab), followed by vedolizumab, ustekinumab and tofacitinib. During follow-up, 71% (470, p=0.05) of patients achieved clinical remission and 36% (134, p=0.03) achieved mucosal healing. The 6 months milestone for persistence was reached in 78% (530) of cases. Almost half of patients (47%, 316 patients) persisted on their current treatment for over 12 months. Overall, an adverse reaction was reported for 67 (10.4%) patients, with no lethal events. Conclusions: Population of biologic-experienced IBD patients in Romania is increasing and is becoming more difficult to achieve long-term disease control. Discontinuation rates for advanced therapies are high. [ABSTRACT FROM AUTHOR]

Introduction: Despite being one of the most frequent chronic digestive diseases worldwide, with a prevalence of 1%, celiac disease (CD) remains severely underdiagnosed. Among the instruments used to improve its diagnostic rate, hematologic parameters have been proposed as screening tests to select patients with an increased probability of having CD. Assessment of coagulation is included in routine check-ups, and CD has been reported to be associated with coagulopathy. We aimed to assess if subtle changes in coagulation tests could be used in clinical practice to prompt testing for CD. Methods: We retrospectively recruited all patients with clinical suspicion for CD during a study period of 7 years (between 2015 and 2022), who were tested using IgA tissue transglutaminase (tTG) serology and serum total IgA (IgG tTG in case of IgA deficiency) and who underwent upper gastrointestinal endoscopy with multiple biopsy sampling of the duodenal bulb and distal duodenum. We stratified patients into three groups: newly diagnosed CD, gluten-free diet-treated CD, and non-CD controls. Results: Altogether, there were 133 CD patients (71 newly diagnosed, 62 GFD-treated) and 57 non-CD controls. Mean age and gender distribution were similar among the three groups: 43.3 years for newly diagnosed CD, 41.6 years for non-CD controls, and 44 years for GFD-treated CD patients, with a male gender distribution of 21.1%, 28%, and 24.1%, respectively. Among the included newly diagnosed CD patients, 14% had a prolonged INR. The mean INR was slightly higher in newly diagnosed CD patients, compared to GFD-treated CD patients and non-CD controls: 1.12 ± 0.30, 1.02 ± 0.83, and 1.00 ± 0.08, respectively (p = 0.009). Consequently, prothrombin activity was slightly lower in newly diagnosed CD patients, compared to GFD-treated CD and non-CD controls: 94.9 ± 19.3%, 102.3 ± 12.8%, and 101.9 ± 15.15, respectively. Interestingly, after GFD, the mean INR and prothrombin activity of CD individuals reached a value similar to that of non-CD controls. Conclusions: Subtle changes in INR, defined as a value within the normal range, but closer to the upper limit, could be an indicator of probability for CD. [ABSTRACT FROM AUTHOR]

Hepatocellular adenomas are benign endothelial tumors of the liver, mostly associated with female individual users of estrogen-containing medications. However, the precise factors underlying the selective development of hepatic adenomas in certain females remain elusive. Additionally, the conventional profile of individuals prone to hepatic adenoma is changing. Notably, male patients exhibit a higher risk of malignant progression of hepatocellular adenomas, and there are instances where hepatic adenomas have no identifiable cause. In this paper, we theorize the role of the human gastrointestinal microbiota, specifically, of bacterial species producing β-glucuronidase enzymes, in the development of hepatic adenomas through the estrogen recycling pathway. Furthermore, we aim to address some of the existing gaps in our knowledge of pathophysiological pathways which are not yet subject to research or need to be studied further. As microbial β-glucuronidases proteins recycle estrogen and facilitate the conversion of inactive estrogen into its active form, this process results in elevated levels of unbound plasmatic estrogen, leading to extended exposure to estrogen. We suggest that an imbalance in the estrobolome could contribute to sex hormone disease evolution and, consequently, to the advancement of hepatocellular adenomas, which are estrogen related. [ABSTRACT FROM AUTHOR]

Despite the extensive recent development of different techniques for endoscopic evaluation for both diagnostic and therapeutic reasons, the small bowel remains quite difficult to visualize. Capsule endoscopy and device assisted enteroscopy are presently considered the best diagnostic tools for examination of small bowel disorders, assessing diverse pathologies such as obscure gastrointestinal bleeding, iron deficiency anemia, Crohn disease, small bowel tumors and polyposis syndromes. Like any other imagistic method, it has specific indications, and contraindications, and possibly it is more important to consider limitations. In order to obtain a better result, it is necessary to respect the procedural quality indicators. Among them the use of prokinetics - diverse pharmacological substances increasing the success rate of capsule endoscopy have raised debates. Capsule endoscopy small bowel evaluation is a reliable, non-invasive and safe with many advantages and minimum risks, with a proper selection of patients, and can be used as first line investigation. [ABSTRACT FROM AUTHOR]

Celiac disease (CD) is a lifelong chronic autoimmune systemic disease that primarily affects the small bowel of genetically susceptible individuals. The diagnostics of adult CD currently rely on specific serology and the histological assessment of duodenal mucosa on samples taken by upper digestive endoscopy. Because of several pitfalls associated with duodenal biopsy sampling and histopathology, and considering the pediatric no-biopsy diagnostic criteria, a biopsy-avoiding strategy has been proposed for adult CD diagnosis also. Several endoscopic changes have been reported in the duodenum of CD patients, as markers of villous atrophy (VA), with good correlation with serology. In this setting, an opportunity lies in the automated detection of these endoscopic markers, during routine endoscopy examinations, as potential case-finding of unsuspected CD. We collected duodenal endoscopy images from 18 CD newly diagnosed CD patients and 16 non-CD controls and applied machine learning (ML) and deep learning (DL) algorithms on image patches for the detection of VA. Using histology as standard, high diagnostic accuracy was seen for all algorithms tested, with the layered convolutional neural network (CNN) having the best performance, with 99.67% sensitivity and 98.07% positive predictive value. In this pilot study, we provide an accurate algorithm for automated detection of mucosal changes associated with VA in CD patients, compared to normally appearing non-atrophic mucosa in non-CD controls, using histology as a reference. [ABSTRACT FROM AUTHOR]

Background and Objectives: Glucose metabolism alterations are very common in solid pancreatic lesions, particularly in pancreatic cancer. Similarly, diabetes and especially new-onset diabetes (NOD) have been associated with the malignant transformation of pancreatic cysts. We aimed to assess the prevalence and relevant associations of glycemic abnormalities in pancreatic cystic lesions (PCLs) in a retrospective analysis. Materials and Methods: We retrospectively recruited all patients who underwent endoscopic ultrasound for a PCL over a period of 36 months (January 2018 to December 2021). Final diagnosis was set by means of tissue acquisition, surgery, followup, or board decision. Demographic and clinical data, laboratory workup, and imaging features were extracted from the patients' charts according to a predefined protocol. We considered fasting blood glucose (FBG) and HbA1c values and stratified the patients as nondiabetic (FBG ≤ 99 mg/dL, HbA1c ≤ 5.6%, no history of glycemic abnormalities), prediabetic (FBG 100-125 mg/dL, HbA1c 5.7-6.4%), or diabetic (long-lasting diabetes or NOD). Results: Altogether, 81 patients were included, with a median age of 66 years, and 54.3% of them were male. The overall prevalence of fasting hyperglycemia was 54.3%, comprising 34.6% prediabetes and 22.2% diabetes, of which 16.7% had NOD. The mean FBG and HbA1c levels were higher in malignant and premalignant PCLs (intraductal papillary mucinous neoplasm (IPMN), mucinous cystic neoplasm (MCN), cystadenocarcinoma, and cystic neuroendocrine tumor) compared to the benign lesions (pseudocysts, walled-off necrosis, and serous cystadenoma): 117.0 mg/dL vs. 108.3 mg/dL and 6.1% vs. 5.5%, respectively. Conclusions: Hyperglycemia and diabetes are common in PCLs, with a high prevalence in premalignant and malignant cysts. Screening and follow-up for glycemic abnormalities should be routinely conducted for PCLs, as they can contribute to a tailored risk assessment of cysts. [ABSTRACT FROM AUTHOR]

Background & 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. [ABSTRACT FROM AUTHOR]

Metastasis to the pancreas represents a small proportion of all pancreatic malignancies. Among primary tumors that metastasize to the pancreas, renal cell carcinoma (RCC) is one of the most common causes of metastatic pancreatic lesions. We herein report a case series of three patients with pancreatic metastasis from RCC. The first is a 54-year-old male with a history of left nephrectomy for RCC, in whom an isthmic pancreatic mass suggestive of a neuroendocrine lesion was found during oncological follow-up. Endoscopic ultrasound (EUS)-guided fine needle biopsy (FNB) identified pancreatic metastasis of RCC and the patient was referred for surgery. The second case is a 61-year-old male, hypertensive, diabetic, with left nephrectomy for RCC six years previously, who complained of weight loss and was found with a hyperenhancing mass in the head of the pancreas and a lesion with a similar pattern in the gallbladder. EUS-FNB from the pancreas proved to be a metastatic pancreatic lesion. Cholecystectomy and treatment with tyrosine kinase inhibitors were recommended. The third case is a 68-year-old dialysis patient referred for evaluation of a pancreatic mass, also confirmed by EUS-FNB, who was started on sunitinib treatment. We report a literature summary on epidemiology and clinical features, diagnosis and differential diagnosis and treatment and outcomes in pancreatic metastasis of RCC. [ABSTRACT FROM AUTHOR]

Vitamin D deficiency is one of the most common medical conditions, with approximately one billion people having low vitamin D levels. Vitamin D is associated with a pleiotropic effect (immunomodulatory, anti-inflammatory and antiviral), which can be essential for a better immune response. The aim of this research was to evaluate the prevalence of vitamin D deficiency/insufficiency in hospitalized patients focusing on demographic parameters as well as assessing the possibility of its associations with different comorbidities. Of 11,182 Romanian patients evaluated in the study over 2 years, 28.83% had vitamin D deficiency, 32.11% insufficiency and 39.05% had optimal vitamin D levels. The vitamin D deficiency was associated with cardiovascular disorders, malignancies, dysmetabolic disorders and SARS-CoV2 infection, older age and the male sex. Vitamin D deficiency was prevalent and showed pathology association, while insufficiency of vitamin D (20–30 ng/mL) had lower statistical relevance and represents a grey zone in vitamin D status. Guidelines and recommendations are necessary for homogeneity of the monitoring and management of inadequately vitamin D status in the risk categories. [ABSTRACT FROM AUTHOR]

Esophageal stroke, also known as acute esophageal necrosis or Gurvits syndrome, is an entity that has gained more and more recognition in the last two decades. It is also named "black esophagus" because of striking black discoloration of the esophageal mucosa, with an abrupt transition to normal mucosa at the gastroesophageal junction. Its most common clinical presentation is represented by upper gastrointestinal bleeding and esophagogastroduodenoscopy is the main diagnostic tool. Among the etiopathogenetic and multiple predisposing factors described are hypovolemia, shock state, ischemia, congestive heart failure, acute renal failure, infections, trauma, and diabetes mellitus. Current management of this condition consists of treating the underlying pathology, nil per os, and antacid administration in uncomplicated cases. Although most of the cases have favorable prognosis, complications such as pneumomediastinum or esophageal stricture may occur and fatal cases are a consequence of underlying comorbidities. [ABSTRACT FROM AUTHOR]

Background: In patients with chronic hepatitis C (CHC), obesity is involved in the pathogenesis of insulin resistance, fatty liver disease and progression of fibrosis. The objective of this study was to compare a normoglucidic low-calorie diet (NGLCD) with a low-fat diet (LFD) among participants with CHC. Aimed to measure the impact of dietary changes in reduction of insulin resistance, obesity but also in steatosis and fibrosis.Methods: Randomized, controlled trial in three medical centers with assessments at baseline, 6 months and 12 months. Participants were patients over 35 years with chronic hepatitis C (n = 120) with BMI over 25 kg/m². We evaluated the effects of NGLCD vs. LFD in weight management and metabolic improvement. The primary endpoint was to measure the impact of dietary changes through nutritional intervention in reversibility of insulin resistance, obesity, steatosis, and fibrosis. We performed anthropometric measurements, fasting glucose profile, serum lipids, liver profile, blood count at baseline, 6 and 12 months. Steatosis was evaluated using ultrasonographic criteria. Liver fibrosis was non-invasively assessed.Results: After 6 and 12 months of intervention, both groups had a significant decrease in caloric consumption. At 6 months, weight loss was greater in the NGLCD group (-5.02 ± 3.43 kg vs. -4.1 ± 2.6 kg; p = 0.002) compared to the LFD group. At 1-year, however, weight loss was similar in both groups (-3.9 ± 3.3 kg vs. -3.1 ± 2.6 kg; p = 0.139). At 12 months, fasting plasma glucose, fasting plasma insulin, and HOMA-IR had significant improvements in both groups. With both diets aspartate aminotransferase (AST), alanine aminotransferase (ALT), gamma-glutamyl transpeptidase (GGT) decreased with significant differences; also there were significant improvements in AST/ALT ratio, Forns fibrosis index. The two diets were associated with reduction of both the prevalence and the severity of steatosis (all p < 0.001). At 12 months, total cholesterol, HDL-cholesterol, triglycerides improved in both groups (all p < 0.05).Conclusions: The present study establishes the benefits of low-calorie diet and low-fat diet in management of patients with hepatitis C regarding improvement of insulin resistance, steatosis and also fibrosis.Overweight or obese patients with CHC undergoing a lifestyle intervention (specific dietary intervention and physical activity) for 1-year had significant improvements in body weight, lipid and hepatic profile.Trial Registration: PNCI2-3343/41008/2007. [ABSTRACT FROM AUTHOR]

Background: Coeliac disease (CD), due to its protean clinical manifestation, is still very under diagnosed in adults and delays in diagnosis may take years and even decades. Simple tools to find cases in primary care may help to identify patients for further diagnostic tests. We have evaluated the usefulness of an on site rapid fingertip whole blood point-of-care test (POCT) for such a purpose.Methods: As CD is known to run within families, we tested 148 healthy relatives of 70 Romanian index cases with biopsy-proven CD (87% of all first-degree family members, median age 36 years) for the presence of circulating autoantibodies. In addition to performing the POCT (which measures blood erythrocyte self-TG2-autoantibody complexes) on site, blood was drawn for later evaluations of serum IgA-class endomysial antibodies (EMA). EMA-positive sera were further tested for transglutaminase 2 antibodies (TG2-IgA). All serological parameters were analyzed blindly in a centralized laboratory that had no knowledge of the on site POCT result. Endoscopic small intestinal biopsies was recommended for all POCT- or EMA-test positive subjects.Results: In on site testing the POCT was positive in 12/148 first-degree relatives (8%) and all these subjects were also serum EMA-positive. A positive EMA test was found only in one other subject. All remaining 135 healthy first-degree relatives were negative for both POCT and EMA. Four subjects positive for both POCT and EMA were negative for TG2-IgA. Ten out of thirteen of the antibody-positive subjects agreed to undergo endoscopy. The POCT was found to be positive in 8/9 first-degree relatives having coeliac-type mucosal lesions of grade Marsh 2 (n = 3) or Marsh 3 (n = 6). The three POCT-positive subjects not agreeing to undergo endoscopy were also both EMA- and TG2-IgA-positive.Conclusion: The fingertip whole blood rapid POCT might fulfill the unmet need for a simple and cheap case-finding biomarker for early detection and presumptive diagnosis of CD. Confirmatory studies are warranted in adult case-finding in specialized outpatient clinics and in primary care. [ABSTRACT FROM AUTHOR]

Although pancreatic cancer (PC) was considered in the past an orphan cancer type due to its low incidence, it may become in the future one of the leading causes of cancer death. Pancreatic ductal adenocarcinoma (PDAC) is the most frequent type of PC, being a highly aggressive malignancy and having a 5-year survival rate of less than 10%. Non-modifiable (family history, age, genetic susceptibility) and modifiable (smoking, alcohol, acute and chronic pancreatitis, diabetes mellitus, intestinal microbiota) risk factors are involved in PC pathogenesis. Chronic inflammation induced by various factors plays crucial roles in PC development from initiation to metastasis. In multiple malignant conditions such as PC, cytokines, chemokines, and growth factors activate the class I phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT)/mammalian target of rapamycin (mTOR) (PI3K/AKT/mTOR) signaling pathway, which plays key roles in cell growth, survival, proliferation, metabolism, and motility. Currently, mTOR, AKT, and PI3K inhibitors are used in clinical studies. Moreover, PI3K/mTOR dual inhibitors are being tested in vitro and in vivo with promising results for PC patients. The main aim of this review is to present PC incidence, risk factors, tumor microenvironment development, and PI3K/AKT/mTOR dysregulation and inhibitors used in clinical, in vivo, and in vitro studies. [ABSTRACT FROM AUTHOR]

The article describes the case of a 68-year old male patient who was diagnosed with transverse colon varices associated with ductal pancreatic adenocarcinoma. The patient underwent upper gastrointestinal endoscopy, contrast-enhanced thoracic and abdominal computed tomography. Laboratory findings showed mild inflammatory syndrome, hyperglycemia, lesion on the body and tail of the pancreas and left adrenal gland and splenic veins, multiple abdominal and pulmonary adenopathies and hepatic lesions.

The systemic inflammatory syndrome concept is one of the foundations that stand at the basis of revolutionary modern and future therapies, based on the in-depth understanding of the delicate mechanisms that govern the collaboration between the systems and organs of the human body and, at the same time, the fine balance that ensures a reproach-free operation. An interesting concept that we propose is that of the environment-inadequacy status, a concept that non-specifically incorporates all the situations of the organism's response disorders in the face of imprecisely defined situations of the environment. The correlation between these two concepts will define the future of modern medicine, along with the gene-adjustment mechanisms. Psoriasis is a clear example of an inadequate body response as a result of exposure to as of yet undefined triggers with an excessive systemic inflammatory reaction and hitherto insufficiently controllable. Modern biological therapies, such as TNF-α, IL-12 family, and IL-17 inhibitors, are intended to profoundly reshape the cytokine configuration of patients with inflammatory diseases such as psoriasis, with tremendous success in disease control. Yet, because of the important roles of cytokines in cancer promotion and control, concern was raised about the fact that the use of biologicals may alter immune surveillance and promote cancer progression. Both theoretical and practical data nevertheless showed that the treatment-induced control of cytokines may be beneficial for reducing the inflammatory milieu that promotes cancer and such have a beneficial role in maintaining health. We briefly present the intricate roles of those cytokine families on cancer control, with some debates on if their inhibition might or might not promote additional tumoral development. [ABSTRACT FROM AUTHOR]

Pancreatic exocrine and endocrine dysfunctions often come together in the course of pancreatic diseases as interdependent manifestations of the same organ. However, the mechanisms underlying the bidirectional connection of the exocrine and endocrine pancreas are not fully understood. In this review, we aimed to synthetize the current knowledge regarding the effects of several exocrine pancreatic pathologies on the homeostasis of β-cells, with a special interest in the predisposition toward diabetes mellitus (DM). We focused on the following pancreatic exocrine diseases: chronic pancreatitis, acute pancreatitis, cystic fibrosis, pancreatic cancer, pancreatic resections, and autoimmune pancreatitis. We discuss the pathophysiologic mechanisms behind the impact on β-cell function and evolution into DM, as well as the associated risk factors in progression to DM, and we describe the most relevant and statistically significant findings in the literature. An early and correct diagnosis of DM in the setting of pancreatic exocrine disorders is of paramount importance for anticipating the disease's course and its therapeutical needs. [ABSTRACT FROM AUTHOR]

Background & Aims: Gastroesophageal reflux disease (GERD) is a common condition present in daily practice with a wide range of clinical phenotypes. In this line, respiratory conditions may be associated with GERD. The Romanian Societies of Gastroenterology and Neurogastroenterology, in association with the Romanian Society of Pneumology, aimed to create a guideline regarding the epidemiology, diagnosis and treatment of respiratory conditions associated with GERD. Methods: Delphi methodology was used and eleven common working groups of experts were created. The experts reviewed the literature according to GRADE criteria and formulated 34 statements and recommendations. Consensus (>80% agreement) was reached for some of the statements after all participants voted. Results: All the statements and the literature review are presented in the paper, together with their correspondent grade of evidence and the voting results. Based on >80% voting agreement, a number of 22 recommendations were postulated regarding the diagnosis and treatment of GERD-induced respiratory symptoms. The experts considered that GERD may cause bronchial asthma and chronic cough in an important number of patients through micro-aspiration and vagal-mediated tracheobronchial reflex. GERD should be suspected in patients with asthma with suboptimal controlled or after exclusion of other causes, also in nocturnal refractory cough which needs gastroenterological investigations to confirm the diagnosis. Therapeutic test with double dose proton pump inhibitors (PPI) for 3 months is also useful. GERD induced respiratory conditions are difficult to treat; however, proton pump inhibitors and laparoscopic Nissen fundoplication are endorsed for therapy. Conclusions: This guideline could be useful for the multidisciplinary management of GERD with respiratory symptoms in current practice. [ABSTRACT FROM AUTHOR]

Majority of colorectal cancer apears through malignant transformation of adenomatous polyps, following a series of changes that start with neoplasia with different grades of displasia. Restrospective studies have shown that finding, treatting and surveilance of neoplastic lesions of colon may reduce the mortality caused by colorectal cancer. The therapeutic and surveillance decision is made based on endoscopic and morphopathologic features of the lesion. [ABSTRACT FROM AUTHOR]

The aim of this study was to investigate the perspective of Romanian patients with Sjögren syndrome (SS) on various aspects of the disease during the SARS-CoV-2 outbreak, including both the impact of COVID-19 on the disease itself as well as the effects of vaccination against SARS-CoV-2 in this group of patients. The study is an online questionnaire-based survey. We received responses from 137 SS patients. Regarding the general emotional status, 33 patients (24.0%) and 47 patients (34.3%) declared to have been sadder/depressive and more agitated/anxious during the SARS-CoV2 outbreak, respectively. During the lockdown, 49 (33.7%) patients strictly and 77 patients (56.2%) did their best to respect the home isolation measures. The income was unchanged for most of the patients (94 patients, 68.6%). Regarding access to healthcare providers, 27 patients (18.7%) postponed the consultation for fear of getting SARS-CoV2. In our study group, 31 patients (22.6%) responded that they have had COVID-19. Only one patient was completely asymptomatic, while the most frequently declared symptom was weakness (84.0%). In 17 patients among the respondents (68%) the symptoms lasted for at least 2 weeks; the most frequent long-lasting symptoms were fatigue (40.0%) and weakness (36.0%). Out of all the respondents, 53 patients (41.4%) were vaccinated against SARS-CoV2 with at least one dose. After the first dose, the most prevalent side effect was pain at the site of injection (89.2%), followed by weakness (25.0%) and myalgias (21.4%). This information will be useful for developing special programs dedicated to SARS-CoV2 infection and vaccination in patients with SS and other autoimmune diseases. [ABSTRACT FROM AUTHOR]

Introduction: Systemic lupus erythematosus (SLE) is a complex autoimmune pathology that can involve any organ. Lupus-related acute pancreatitis (AP) is, together with lupus mesenteric vasculitis, an important cause of SLE-induced acute abdominal pain. Methods: A literature search was conducted using the terms "Pancreatitis" and "Lupus Erythematosus, Systemic" on PubMed/Medline and Web of Science from January 2007 to January 2020. Clinical characteristics, diagnostic approach, and treatment principles in SLE-related AP are presented in this review. Results: Mainly retrospective reports were identified. The reported incidence of SLE-associated AP ranges from 0.9 to more than 5% of patients. A total of 264 SLE patients were found in the selected research, with a net female predominance (sex ratio 9:1) and mean age of 31.4 years. Abdominal pain was virtually present in all cases. AP occurrence was more frequent in SLE patients with short disease duration, high activity scores, and multiorgan involvement. The AP definition was based on currently available guidelines and after exclusion of any other known causes (including iatrogenic, i.e. drugs), a diagnosis of "idiopathic" SLE-related AP might be sustained. Management is difficult, as there is no standardized therapeutic approach. Of note, glucocorticoid use remains still controversial as, especially for high doses, subsequent pancreatic injury may occur. Monitoring serum lipase levels after high dose steroids might be considered. One study reported beneficial prognostic effect of plasma exchange. Moreover, AP in SLE might raise awareness about macrophage activation syndrome association. Mortality up to one third of AP cases in SLE was reported. Conclusion: The SLE-related AP is a rare, but severe, life-threatening complication. Corticosteroids must be used with caution. Plasma exchange could be considered in selected cases. [ABSTRACT FROM AUTHOR]

Mucosa-associated lymphoid tissue lymphoma (MALT) is seldom considered a diagnosis hypothesis in symptomatic patients. These lymphomas present as a main risk factor for chronic gastritis due to Helicobacter pylori infection. H. pylori leads to chronic inflammation, producing lymphoid tissue in the stomach mucosa (MALT) possibly leading to malignant transformation. Even though H. pylori remains one of the most important factors in the development of MALT lymphoma, it is not mandatory in the evolution of MALT lymphoma since high-grade lymphomas present a lower prevalence of H. pylori. The prevalence of H. pylori is indirectly proportional with the progression into the gastric wall. Mucosal and submucosal MALT lymphomas have a higher prevalence of the bacteria. However, genetic factors remain a risk factor especially if eradication treatment fails. Even though a low percentage of MALT lymphomas are H. pylori-negative, some respond to antibiotic eradication treatment. This can be explained either by the immunomodulatory effect of antibiotics or by other infectious sources such as Helicobacter heilmannii and Campylobacter jejuni (small bowel lymphoma). Treatment in MALT gastric lymphoma was a breakthrough since it was the first time in oncology where tumours were cured by antibiotic therapy, leading us to wonder if MALT lymphomas are infectious disease or not? [ABSTRACT FROM AUTHOR]

Introduction. Despite being one of the most frequent chronic digestive diseases worldwide, with a prevalence of 1%, celiac disease (CD) remains severely underdiagnosed. Among the instruments used to improve its diagnostic rate, hematologic parameters have been proposed as screening tests to select patients with an increased probability of having CD. Assessment of coagulation is included in routine check-ups, and CD has been reported to be associated with coagulopathy. We aimed to assess if subtle changes in coagulation tests could be used in clinical practice to prompt testing for CD. Methods. We retrospectively recruited all patients with clinical suspicion for CD during a study period of 7 years (between 2015 and 2022), who were tested by IgA tissue transglutaminase (tTG) serology and serum total IgA (IgG tTG in case of IgA deficiency) and underwent upper gastrointestinal endoscopy with multiple biopsy sampling of the duodenal bulb and distal duodenum, in line with currently available guidelines. According to this evaluation, patients were stratified as either CD or non-CD controls. Also, we included gluten-free diet (GFD) treated CD patients, as a second control group. Routine laboratory workup including coagulation tests was performed in all patients. We excluded outliers, consisting of 2 patients with incoagulable INR and patients with other potential causes for altered coagulation tests (anticoagulants, liver impairment, etc.). Results. Altogether, there were 51 newly diagnosed CD patients, 42 non-CD (controls), and 49 GFDtreated CD patients. Mean age and gender distribution were similar among the three groups. The mean age of newly-diagnosed CD patients, GFDtreated CD patients, and controls was 43.1 years, 45.9 years, and 42.4 years, respectively, with a male gender distribution of 19.6%, 18.3%, and 28.5%. Among the included patients 13% had a prolonged INR. The mean INR was slightly higher in newly diagnosed CD patients, compared to GFD-treated CD patients and non-CD controls: 1.12, 1.01, and 0.99, respectively. Consequently, prothrombin activity was slightly lower in newly diagnosed CD patients, compared to GFD-treated CD and non-CD controls. Interestingly, after GFD, the mean INR of CD individuals reached a value similar to that of non-CD controls. Conclusions. Subtle changes in INR, defined as a value within the normal range, but closer to the upper limit, could be an indicator of probability for CD. [ABSTRACT FROM AUTHOR]

Acute pancreatitis (AP) represents an inflammatory condition,-with a wide spectrum of local and systemic complications. Early stratification of severity of pancreatitis is an important step in guiding the management of the disease and improving outcomes. Throughout the years many researchers have looked at various risk stratification parameters which could be used from the admission of patients, however current available scores are cumbersome. Our aim was to evaluate the role of biochemical and hematological parameters in the early stratification of severity of AP, regarding the length of hospitalization. We conducted an observational study which included 100 patients with AP admitted to the Gastroenterology Department over a period 18 months. AP diagnosis was set according to 2013 ACG criteria. Demographic, clinical and imaging data related to the pancreatitis flare were collected from their charts. Length of hospital stay was used as surrogate marker for severity of AP. We evaluated different biochemical and hematological parameters which influenced the length of hospitalization. Several hematological parameters and ratio did not correlate with length of hospital stay in our study cohort, however there was a significant relation of hyperglycemia and alkaline phosphatase levels with hospitalization duration. Early risk stratification in AP remains difficult with routine blood work done at admission. Glycemic control and serum level of alkaline phosphatase seems to be correlated with length of hospital stay. [ABSTRACT FROM AUTHOR]

Background. Acute pancreatitis represents an inflammatory disease with different grades of severity, ranging from mild to severe presentation. In current practice there are a lot of biomarkers used in diagnosis and prognosis of pancreatitis. The aim of this study was to evaluate de differences between a group with acute pancreatitis and a group of healthy people regarding the neutrophil to lymphocyte ratio (NLR), thrombocyte to lymphocyte ratio (TLR), as these two could help in the evaluation of prognosis and severity of acute pancreatitis. Method. The study had two groups: group A, included 100 patients with acute pancreatitis and group B - 30 healthy people. Results. In the group A there were 65% male and 35 % female with a mean age of 58.07±15.10 years, in the group B there were 50% male and 50% female with a mean age of 48.06±15.47 years. The majority of the people included in both groups were from the urban provenience. We obtained an important difference between group A and group B regarding the neutrophil to lymphocyte ratio and thrombocyte to lymphocyte ratio with an important statistical significance (p<0.001). Conclusion. Neutrophil to lymphocyte ratio and thrombocyte to lymphocyte ratio could be promising biochemical parameters in diagnosis and prognosis of acute pancreatitis. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Recent years have brought additional data on the benefits of prebiotics and probiotics treatment in patients with atopic dermatitis. This review includes all the articles published in PubMed, Scopus, Embase and Cochrane databases until 05.06.2018. The terms used for the search were 'prebiotic', 'probiotic', 'atopic dermatitis', 'Severity Scoring of Atopic Dermatitis', and 'SCORAD'. There was an increase of the intestinal permeability reported in patients with atopic dermatitis and a reduction of the cutaneous microbiome diversity. Probiotics modulate the general microbiome and immune status by improving the intestinal barrier; these effects can be responsible for reducing allergic phenomenon and atopic dermatitis severity. We have structured the results by age groups as infants, 1–18 years, adults, and also pregnancy and lactation. Literature does not offer yet answers on the issues such as the optimal dosing, duration needed to see beneficial effects, the optimal time to start the treatment; the personalized use of probiotics according to colonic dysbiosis may be associated with better results. However, most randomized controlled trials and meta-analyzes support the administration of probiotics for at least 8 weeks in order to obtain beneficial effects in improving severity scoring of atopic dermatitis. [ABSTRACT FROM AUTHOR]

Biosimilars are new drugs, highly similar copies of biological medicines, equally effective and safe but at lower prices. The aim of this brief review is to provide the current status of biosimilars approved in the European Union for dermatological use. We used PubMed for literature search up to June 2018. The keyword 'biosimilars' was searched and 1,691 items were found. From the 1,691 studies, we included 34 articles in our review. Biologics, biosimilars and generics are different types of drugs. Biosimilars are complex molecules produced by a difficult manufacturing process, and changes in product quality may affect its safety and efficacy. Now, there are 9 biosimilar medicines approved by European Medicines Agency (EMA) for plaque psoriasis and hidradenitis suppurativa: Amgevita, Solymbic, Cyltezo, Imraldi, Benepali, Erelzi, Flixabi, Inflectra and Remsima, and the number is increasing. In 2005, EMA issued the first guidelines for approval of biosimilars. Next-generation biologics, called 'biobetters', have the same target or mechanism of action as previously approved biologics, but they have structural changes and an improved formulation. The debate over the future of biosimilars is far from being finished. The explosive development of biological therapy and the emergence of biosimilars represent a significant success in the effort to provide advanced healthcare to patients all over the world. [ABSTRACT FROM AUTHOR]

Background. Groove pancreatitis or paraduodenal pancreatitis represents a rare type of pancreatitis, and can be classified into cystic dystrophy of the duodenal wall in heterotopic pancreas, paraduodenal cyst or myoadenomatosis. Case presentation. We present a case of a 58 year old man, drinker and smoker who was admitted in the Department of Gastroenterology for abdominal pain, weight loss and nausea. From his history we have noticed frequent presentations of recurrent acute pancreatitis in the last two years. Laboratory tests have revealed cholestasis, high value of lipase and high value of amylase, with normal value of CA 19.9. The magnetic resonance from the last two years showed the same appearances: a large and edematous head of pancreas, a thickening of the wall of adjacent duodenum and an inhomogeneous area with cystic transformation in the head of the pancreas. We performed endoscopic ultrasound with fine needle aspiration. The histopathological result showed only inflammatory cells. We have established the diagnosis of groove pancreatitis. Conclusion. Groove pancreatitis represents a rare condition, with an incidence of 0.4%-14% on biopsies. Endoscopic ultrasound is the best method for diagnosis, it could evaluate also the duodenal wall. [ABSTRACT FROM AUTHOR]

Background. Colonoscopy is a common performed procedure in Gastroenterology, and it's widely used for diagnosis, treatment and surveillance of a wide range of conditions and symptoms. Properly performed, it's generally safe, more accurate than a virtual colonoscopy and well-tolerated by patients. The completion of a colonoscopy is defined by cecal intubation with the visualization of colonic mucosa and distal terminal ileum when it's possible. Patients and methods. We reviewed retrospectively all consecutive endoscopies database of the lower digestive tract, done over a period from 2014-2017 in our clinic. The recommended completion based on the latest guidelines ranges from 90-95% completion rate according to the indication. Results. 11214 consecutive colonoscopies were done. Overall cecal intubation was successful in 9456 procedures (87.3%). If we exclude the interventional procedures (414 procedures), where cecal intubation was not necessary, the main reasons of non-intubation were due to intolerance of the patients (388 patients), followed on the second place by patients with obstructive cancer (299 patients). The presence of diverticulosis, poor preparation for colonoscopy and post-surgical adhesions were significant findings in non-successful procedures. Conclusions. In normal daily practice, colonoscopy is completed in 88.01% of the procedures but we think that this result will stimulate the efforts to incorporate more quality measures and time in our endoscopy laboratory. [ABSTRACT FROM AUTHOR]

Background & Aims: Celiac disease (CD) presents with a wide spectrum of extra-digestive symptoms, including hemorrhagic manifestations. The aim of this review was to conduct an extensive analysis of the hemorrhagic events reported in adult CD patients. Methods: Case report and review of the literature. Pubmed (MEDLINE) database search from January 1970 onwards was performed using the medical subject headings [MeSH] terms "celiac disease" AND "blood coagulation disorders", "hemorrhage", "hematoma", "hematuria", "hemoptysis", "epistaxis", "hemosiderosis". Only case reports were identified on the search theme. Information on patients' characteristics, diagnostic features, coagulation parameters, symptomatology duration, and evolution under treatment were systematically collected and summarized. Results: We present the case of a 40-year-old man hospitalized for spontaneous muscular hematomas, in whom CD was diagnosed. We performed a review of the literature and summarized the published case reports of 46 CD patients, aged between 19 and 74 years, 64% of male gender. In 25% of cases, the symptomatology was present for more than 5 years prior to CD diagnosis. The clinical hemorrhagic events were as follows: 15 patients had gastrointestinal bleeding, 9 hemoptysis, 4 epistaxis, 6 hematuria, 8 cutaneous hematoma, petechia or ecchymoses, and only in 1 case hemarthrosis, hemorrhagic vesicular dermatitis, subcortical hemorrhage, or adrenal hemorrhage. Sixty percent of the patients had digestive symptoms, while the rest had only extradigestive CD involvement. The Lane Hamilton syndrome was defined in 15 patients. The evolution under a gluten-free diet was favorable in most cases. Conclusion: This review of case reports aims to increase awareness to hemorrhagic events, rare but possible life-threatening conditions, as part of the CD clinical spectrum. To the best of our knowledge, this is the first review of all types of hemorrhagic events in adult CD patients. [ABSTRACT FROM AUTHOR]

Background. The diagnosis of chronic adrenal insufficiency is more difficult than acute adrenal insufficiency. The gastrointestinal symptoms are often present and they can be associated with the severity of the insufficiency. Case report. A 28-years old man was admitted at the Gastroenterology Department for nausea and postprandial vomiting, abdominal pain and asthenia. His past medical history reveals persistent vomiting for a year. Clinical examination showed hypotension, mild skin pigmentation and painful abdomen. Laboratory analysis showed hyponatremia. The upper endoscopy revealed: esophagus - mucosal break no longer than 5 mm at the Z line, stomach-congestive folds, hyperemic mucosa near the fornix, there were taken a few biopsies; hyperemic antral mucosa presenting a few erosions; open pylorus, duodenum with normal mucosa. During the hospitalization the patient received treatment with electrolytes, but the hyponatremia was still present. We tested plasmatic cortisol and the ACTH, the obtained values being lower than normal cut-off. Also the TSH and ATPO levels were high. We based the diagnosis of primary adrenal insufficiency on anamnesis, clinical examination and laboratory parameters. Conclusions. Diagnosis of Addison disease is based on clinical orientation. The gastroenterological symptoms are often present. [ABSTRACT FROM AUTHOR]

Background: Alveolar hemorrhage is a potentially life-threatening condition which is usually managed by the pulmonologist. When considering its etiology, there is a rare association that sets the disease into the hands of the gastroenterologist. Case presentation: We report the case of a 48 year-old female who was admitted to the intensive care unit for severe anemia and hemoptysis. On imaging, diffuse pulmonary infiltrates suggestive of alveolar hemorrhage were detected and a diagnosis of pulmonary hemosiderosis was made. She received cortisone therapy and hematologic correction of anemia, with slow recovery. In search of an etiology for the pulmonary hemosiderosis, an extensive workup was done, and celiac disease specific serology was found positive. After confirmation of celiac disease by biopsy, a diagnosis of Lane-Hamilton syndrome was established. The patient was recommended a gluten-free diet and at 6 months follow-up, resolution of anemia and pulmonary infiltrates were observed. Conclusion: Although the association is rare, celiac disease should be considered in a patient with idiopathic pulmonary hemosiderosis. In our case, severe anemia and alveolar infiltrates markedly improved with glucocorticoids and gluten-free diet. [ABSTRACT FROM AUTHOR]

Endoscopic stenting of malignant esophageal stenosis is a very effective palliative treatment, leading to rapid control of dysphagia. This procedure meets an important goal of current oncology therapy, which is improving quality of life. Esophageal stents have evolved in almost 120 years from the rigid plastic tube used by Sir Charter Simmonds, to self-expandable metal stents mostly used nowadays. Biodegradable stents are a very promising solution for benign esophageal stenosis, but they are not suitable for malignant stenosis. Acute complications rate for self-expandable metal stents is beneath 1% for most complications (technical failure, stent dislodgment, perforation, death), but may reach 8% for bleeding (mostly insignificant) or 13% for chest pain (mostly minor pain and swiftly amenable to treatment). Also, the current guidelines recommend against concomitant chemo-radiotherapy and stent placement because of very high rate of complications. There is an interesting new approach in esophageal oncology surgery to use neoadjuvant chemo-radiotherapy and stent just prior to operation, in order to improve nutritional status. In the second part of the article I present a case of malignant stenosis and cutaneous fistula that appeared in a patient with esophageal reconstruction with gastric tube treated for esophageal adenocarcinoma. [ABSTRACT FROM AUTHOR]

Background: Once considered a disease of childhood, celiac disease (CD) is now seen quite frequently in adults also, but with different and various clinical presentation. Little data is currently available about pediatric and adult CD features in Romanian patients. Material and Methods: 38 newly-diagnosed CD patients (17 adults and 21 children) were recruited for this study. The two groups (adult and pediatric) were compared regarding demographic, clinical, serologic and histological data. Results: Regarding demographic data, female gender was predominant in both groups (71% and 67% respectively). Median age was 42 (range 23-83) in the adult CD group and 4 (1-17) in the pediatric CD group. Classic presentation was more frequently seen in children than adults (62% vs. 53%). Altered liver function tests, anemia and iron deficiency were more prevalent in the pediatric group. Children with CD also had higher titers of tTG antibodies (81% over 200 U/l, compared to 29% adults) and a higher frequency of destructive histology on small bowel biopsy (95% Marsh>3a, compared to 76% adults). Conclusion: Significant differences in pediatric and adult CD were seen in our study cohort, regarding clinical, laboratory and histological parameters. CD manifests differently in children and adults. [ABSTRACT FROM AUTHOR]

Background: Primary intestinal lymphangiectasia (Waldmann's disease) is a rare disease characterized by dilated lymphatics in the small bowel leading to an exudative enteropathy with lymphopenia, hypoalbuminemia and hypogammaglobulinemia. Case presentation: We report the case of a 23 year-old male who presented with chronic anemia and in whom primary intestinal lymphangiectasia was diagnosed. A low-fat diet along with nutritional therapy with medium-chain triglyceride supplementation improved the protein-losing enteropathy, but did not solve the anemia. Octreotide was also unsuccessful, and after attempting angiographic embolization therapy, limited small bowel resection together with antiplasmin therapy managed to correct the anemia and control the exudative enteropathy. Conclusions: Although primary intestinal lymphangiectasia is usually adequately managed by nutritional therapy, complications such as anemia can occur and can prove to be a therapeutic challenge. [ABSTRACT FROM AUTHOR]

In assessing exocrine pancreatic insufficiency (EPI), its diverse etiologies and the heterogeneous population affected should be considered. Diagnosing this condition remains a challenge in clinical practice especially for mild-to-moderate EPI, with the support of the time-consuming breath test or the coefficient of fat absorption. The fecal elastase-1 test, less precise for the diagnosis, cannot be useful for assessing treatment efficacy. Pancreatic enzyme replacement therapy (PERT) is the mainstay of treatment, whereby entericcoated mini-microspheres are taken with every meal, in progressive doses based on an individual's weight and clinical symptoms. The main indication for PERT is chronic pancreatitis, in patients who have clinically relevant steatorrhea, abnormal pancreatic function test or abnormal function tests associated with symptoms of malabsorption such as weight loss or meteorism. While enzyme replacement therapy is not recommended in the initial stages of acute pancreatitis, pancreatic exocrine function should be monitored for at least 6-18 months. In the case of unresectable pancreatic cancer, replacement enzyme therapy helps to maintain weight and improve overall quality oflife. It is also indicated in patients with celiac disease, who have chronic diarrhea (in spite of gluten-free diet), and in patients with cystic fibrosis with proven EPI. [ABSTRACT FROM AUTHOR]

Colorectal cancer (CRC) is a predominant malignancy worldwide, being the fourth most common cause of mortality and morbidity. The CRC incidence in adolescents, young adults, and adult populations is increasing every year. In the pathogenesis of CRC, various factors are involved including diet, sedentary life, smoking, excessive alcohol consumption, obesity, gut microbiota, diabetes, and genetic mutations. The CRC tumor microenvironment (TME) involves the complex cooperation between tumoral cells with stroma, immune, and endothelial cells. Cytokines and several growth factors (GFs) will sustain CRC cell proliferation, survival, motility, and invasion. Epidermal growth factor receptor (EGFR), Insulin-like growth factor -1 receptor (IGF-1R), and Vascular Endothelial Growth Factor -A (VEGF-A) are overexpressed in various human cancers including CRC. The phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT)/mammalian target of rapamycin (mTOR) and all the three major subfamilies of the mitogen-activated protein kinase (MAPK) signaling pathways may be activated by GFs and will further play key roles in CRC development. The main aim of this review is to present the CRC incidence, risk factors, pathogenesis, and the impact of GFs during its development. Moreover, the article describes the relationship between EGF, IGF, VEGF, GFs inhibitors, PI3K/AKT/mTOR-MAPK signaling pathways, and CRC. [ABSTRACT FROM AUTHOR]