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Background: Liver cells represent an attractive source of cells for autologous regenerative medicine. The present study assesses the liver cells’ stability during in vitro expansion, as a prerequisite for therapeutic use. Results: The human liver cell cultures in this study were propagated efficiently in vitro for at least 12 passages. No significant changes in morphology, intracellular ultrastructures and characteristic markers expression were found during in vitro expansion of cells from all analyzed donors. However, expanded cells derived from male donors of >60 years old, lost the Y chromosome. Conclusion: Liver-derived cell cultures adopt a proliferative, stable mesenchymal phenotype, through an epithelial to mesenchymal transition process. The molecular and phenotypic changes of the cells during propagation are uniform, despite the heterogeneity of the different donors. Loss of Y chromosome occurs after cells’ propagation in elder male donors.

Background and Aims: Inflammatory bowel diseases (IBD) patients management has been challenging during the ongoing coronavirus disease 2019 (COVID-19) pandemic, due to lockdowns, limitation of access to medical facilities and new recommendations regarding patient management. The implications of the COVID-19 pandemic on IBD patients’ management were assessed in our Tertiary Gastroenterology Center in Bucharest, Romania. Methods: Medical records of IBD patients admitted between 15th of March and 15th of August 2020 were retrospectively reviewed and compared to a control cohort of consecutive IBD patients admitted to our unit during the corresponding period of 2019. Results: There was a highly significant shift towards one-day hospitalization during the referral period in 2020 for IBD cases (91% in 2020 vs 82.2% in 2019, p=0.0001). There was no statistically significant difference between the distribution of patient’s gender, IBD phenotype or newly diagnosed IBD cases. A significantly lower proportion of admitted patients received 5-aminosalicylic acid (29% vs 41.2%, p=0.0001), whereas a substantially higher number of patients were prescribed biological therapy in 2020 in comparison to the corresponding 2019-time frame (79.5% vs 57.9%, p

Background and Aims: Bowel ultrasound (BU) is a non-invasive, inexpensive, widely available tool, valuable for inflammatory bowel disease (IBD) assessment. The aim of the present study was to investigate the clinical utility of BU to predict the need to intensify therapy in IBD patients. Methods: One hundred seventeen IBD patients (89 Crohn’s disease, and 28 ulcerative colitis) diagnosis established at least 6 months before enrolment, undergoing maintenance therapy were prospectively included in the study. Bowel ultrasound investigated the following parameters: the bowel wall thickness (BWT), loss of wall stratification, the presence of the bowel wall Doppler signal, the visible lymph nodes, the mucosal hyperechoic spots, and the irregular external bowel wall. The patients were followed-up for 6 months, registering the need to escalate the treatment regimen. Subgroup analyses were conducted for patients requiring immediate treatment intensification (37 subjects), due to active disease at baseline and patients with subsequent treatment intensification, in the 6 months follow-up period (21 cases) in comparison to patients that required no therapeutic optimization (59). Results: During the follow-up, 49.6% of patients needed treatment escalation. All the investigated BU variables were significantly associated with the main outcome. In the multivariate analysis, the mean BWT (p0.91) when compared to traditional biomarkers of active inflammation, such as C reactive protein or fecal calprotectin. Conclusion: Bowel ultrasound could be used as a non-invasive, easy to use diagnostic tool to predict the need to intensify therapy in patients with IBD.

IntroductionSarcopenia, malnutrition, physical deconditioning, and frailty contribute to a significantly altered quality of life (QoL) in patients with cirrhosis and sarcopenia.AimTo investigate the sarcopenia-linked alterations of QoL by SarQoL® questionnaire in patients with end-stage liver disease.MethodsConsecutive patients with liver cirrhosis, admitted to our department between May and August 2021, completed the SarQoL® questionnaire by themselves. They were evaluated for sarcopenia according to the 2019 European Working Group on Sarcopenia in Older People (EWGSOP) definition [hand grip cut-offs and skeletal muscle index (SMI) calculation at CT scan].ResultsA total of 71 patients with liver cirrhosis were included in the study, with a median age of 54 years. Sarcopenia was present in 31.2% of patients with Child-Pugh class A, in 58.3% with class B, and in 93.5% with class C. The SarQoL® score was statistically significant and lower in Child-Pugh class C vs. class B and class A (70.2 vs. 66.5 vs. 52.5 points, p = 0.0002). The SarQoL® score was evaluated according to different complications of cirrhosis, with statistically significant lower scores in patients with sarcopenia (p < 0.0001), in patients with ascites requiring paracentesis (p = 0.0006), and in patients with hepatic encephalopathy (p < 0.0001). A cut-off level of 75.9 points for SarQoL® score can accurately detect sarcopenia in patients with end-stage liver disease [area under the receiver operating characteristic (AUROC) curve of.823, SE of 92.1%, SP of 45.5%, positive predictive value (PPV) and negative predictive value (NPV) of 66 and 83.3%, respectively, correctly classified 73.2% of cirrhotic patients with sarcopenia].ConclusionsThe use of SarQoL® questionnaire in cirrhotic patients can, at the same time, evaluate the quality of life and identify subjects with sarcopenia and altered QoL.

Background An accelerated course of hepatic fibrosis may occur in liver transplantation (LT) patients despite normal or slightly abnormal liver blood tests. Aim To identify screening tools based on blood biomarkers to predict late allograft dysfunction in LT recipients. Methods 174 LT recipients were enrolled. Liver biopsy, liver functional tests, cytokine quantitation in serum, as well as soluble MHC class I polypeptide-related sequence A and B (sMICA/sMICB) and soluble UL16 binding protein 2 (sULBP2) were performed. Results Patients with late graft dysfunction had a significantly higher donor age, lower albumin level, higher alanine (ALT) and aspartate aminotransferase (AST), gamma-glutamyl transpeptidase (GGT), total bilirubin and alkaline phosphatase (ALP), higher sMICA, sULBP2, higher interleukin (IL) 6, interferon γ and lower IL10 in serum as compared to recipients without allograft dysfunction. In order to provide a better statistical accuracy for discriminating 5-year allograft dysfunction from other less progressive subtype of allograft injury, we established a predictive model, based on 7 parameters (serum ALP, ALT, AST, GGT, sMICA, IL6 and albumin) which provided an Area Under the Receiver Operating Characteristics (AUROC) curve of 0.905. Conclusions Blood-based biomarkers can significantly improve prediction of late liver allograft outcome in LT patients. The new developed score comprising serum parameters, with an excellent AUROC, can be reliably used for diagnosing late allograft dysfunction in transplanted patients.

Background: Nowadays, interferon-free therapy using new direct-acting antivirals (DAA) has dramatically increased the cure rate across different HCV-infected patient populations, including groups traditionally viewed as difficult-to-treat (patients with co-infections, cirrhosis and liver transplant – LT recipients) with marked improvement in safety and tolerability.Aim: To present our experience with DAA therapy in LT recipients, as well as to compare pre- and posttreatment liver stiffness (LS) and noninvasive fibrosis scores.Methods: Our cohort consisted of 89 patients with genotype 1 (GT1) recurrent hepatitis C after LT.Seventy six patients received ombitasvir/paritaprevir/ritonavir+dasabuvir+ribavirin and 13 sofosbuvir/ ledipasvir±ribavirin. Fibroscan®, FIB4 and APRI scores were performed in all patients before and 12 weeks after DAA therapy.Results: We analyzed 45 (50.5%) males and 44 (49.5%) females with a mean age of 55±7.7 years. Median time since LT was 20.9 months. At baseline, 53 (59.6%) of patients had severe necroinflammation at Fibromax®; advanced fibrosis (F3, F4) was encountered in 35 (39.4%) and grade 3 steatosis in 33 (37.1%) of LT recipients.End of therapy (EOT) virological response (VR) was 100%. Sustained virological response 12 weeks after therapy (SVR12) was 97.7% in the intention-to-treat analysis and 100% in per protocol analysis. There was a significant improvement in LS between antiviral therapy initiation and SVR12: 11.9±1.05kPa vs 8.8±0.6kPa (p

Background & Aims: Evaluation of severity and extension of gastric atrophy and intestinal metaplasia is recommended to identify subjects with a high risk for gastric cancer. The inter-observer agreement for the assessment of gastric atrophy is reported to be low. The aim of the study was to evaluate the inter-observer agreement for the assessment of severity and extension of gastric atrophy using oriented and unoriented gastric biopsy samples. Furthermore, the quality of biopsy specimens in oriented and unoriented samples was analyzed.Methods: A total of 35 subjects with dyspeptic symptoms addressed for gastrointestinal endoscopy that agreed to enter the study were prospectively enrolled. The OLGA/OLGIM gastric biopsies protocol was used. From each subject two sets of biopsies were obtained (four from the antrum, two oriented and two unoriented, two from the gastric incisure, one oriented and one unoriented, four from the gastric body, two oriented and two unoriented). The orientation of the biopsy samples was completed using nitrocellulose filters (Endokit®, BioOptica, Milan, Italy). The samples were blindly examined by two experienced pathologists. Inter-observer agreement was evaluated using kappa statistic for inter-rater agreement. The quality of histopathology specimens taking into account the identification of lamina propria was analyzed in oriented vs. unoriented samples. The samples with detectable lamina propria mucosae were defined as good quality specimens. Categorical data was analyzed using chi-square test and a two-sided p value

Background The IBD patients management has been challenging during the ongoing COVID-19 pandemic, due to lockdowns, limitation of access to medical facilities and new recommendations regarding patient management. The implications of the COVID-19 pandemic on IBD patient’s management were assessed in our Tertiary Gastroenterology Centre in Bucharest, Romania. Methods Using the hospital’s medical system, records of IBD patients admitted between 15th of March and 15th of August 2020 have been retrospectively reviewed and compared to a control cohort of consecutive IBD patients admitted to our unit during the corresponding period of 2019, registering the epidemiological features, patient management and the incidence of COVID-19 infection. Results 410 individual IBD cases were managed in our unit in 2020 compared to 532 in 2019, with a significant shift towards one-day hospitalization: 1059 admissions (9% ward hospitalizations, 91% one-day hospitalizations) compared to 1327 cases in the corresponding period of 2019 (17.8% ward hospitalizations, 82.2% one day hospitalizations). There was no statistically significant difference between the distribution of patient’s gender, IBD phenotype or newly diagnosed IBD cases between the two periods. A significantly lower proportion of admitted patients received 5-aminosalicylic acid (29% vs. 41.2%, p=0.0001), whereas a substantially higher number pf patients were prescribed biological therapy in 2020 in comparison to the corresponding 2019-time frame (79.5% vs 57.9%, p0.05). Moreover, from our previously diagnosed patients, 7.1% needed the initiation of biological therapy due to disease flare-up (vs. 4.3% in 2019, p=0.003). During the study period in 2020, seven IBD patients (1.7%) were diagnosed with severe acute respiratory syndrome coronavirus 2 (SARS-Cov2) infection, all of them with mild symptoms without impact on the IBD course. Conclusion The COVID-19 pandemic led to reorganizing medical care, restricting the hospital admissions in favour of severe IBD cases, favouring telemedicine for mild disease and optimization of treatment for moderate to severe IBD with an increased use of biologicals aimed to maximize the risk/benefit ratio. Incidence of SARS-Cov2 infection during the first wave of COVID-19 infection in our study group was 1.7% and did not adversely impact the IBD disease course.

Background & Aims: Ombitasvir/Paritaprevir/ritonavir/Dasabuvir (OBV/PTV/r+DSV) is one of the elective direct-acting antivirals (DAAs) recommended by international guidelines and the only one covered by the National Insurance System in Romania until November 2016. Our aim was to present the first prospective Romanian cohort evaluating the effectiveness and safety in clinical practice of this 3DAA combination in patients with HCV genotype-1b Child A liver cirrhosis.Methods: 681 patients received OBV/PTV/r+DSV+RBV for 12 weeks and were assessed clinically and biologically at baseline, week 4, 8, 12 (end of treatment, EOT), and 12 weeks after therapy (sustained viral response, SVR).Results: Per protocol, EOT virological response was 99.8% and SVR12 rate was 99.4%. Adverse events were present in 36.4% of patients. Permanent discontinuation of 3DAA regimen due to side effects was reported in 11 patients (1.6%). In 47.6% (185/389) of patients, Transient Elastography values were >20kPa (defined as clinically significant portal hypertension, CSPH) at baseline. Independent variables associated with CSPH were: baseline cholesterol level (p=0.003), platelet count

Background Bowel ultrasonography (BUS) is an accurate imaging method for detecting and monitoring inflammatory bowel disease (IBD) patients. This technique is recommended by current guidelines besides gold standard endoscopic assessment in managing IBD patients. Several BUS characteristics strongly correlate with biological markers of inflammation suggesting that these tests could be used in monitoring IBD patients but is yet unknown how these features predict the patient’s evolution. Methods Our study included 95 consecutive IBD patients (24 diagnosed with ulcerative colitis, 71 with Crohn’s disease) with both active and inactive disease at presentation. IBD diagnosis was established endoscopically and histologically. Patients with superimposed infection (viral or bacterial) and patients that had solely rectal involvement of the disease were excluded. BUS was conducted at baseline by one skilled examiner blinded to biological data. Biological markers were evaluated at baseline and all cases were prospectively followed-up for the need of therapy escalation during the next 6 months. The following BUS characteristics were registered in every patient: bowel wall thickness, alteration of wall structure, thickened mucosa or submucosa, presence of hyperechoic spots in the mucosal wall, irregularity of the external wall, Doppler signal, presence of mesenteric hypertrophy, presence of lymph nodes, and an overall assessment of the examination. No special preparation was needed before BUS. Results Of all the monitored sonographic features, the following characteristics correlated with the need of increasing treatment in the following 6 months: bowel wall thickness, altered structure of the wall, hypertrophic mucosa, Doppler signal, and the overall assessment of the examination (p < 0.001). The presence of the lymph nodes, hyperechoic spots in the mucosa, thickened submucosa and the irregularity of the external wall were not statistically significant correlated with the need for treatment escalation. The strongest correlation with the need for increasing treatment was documented for a mean bowel wall thickness > 5 mm and for Doppler signal presence in the bowel wall (p < 0.00001). In the multivariate analysis, Doppler signal presence was the only independent predictor for the need treatment escalation during a 6-month follow-up. Conclusion The most important sonographic features with an impact on therapeutic decision making in IBD patients are: bowel wall thickness, Doppler signal, altered stratification of the wall and mesenteric hypertrophy. In our analysis, the Doppler signal was the only independent predictor for the need for step-up therapy.

Background and objective: The incidence of inflammatory bowel disease (IBD) over the past years in Romania has been on the rise, but epidemiologic data are lacking. The aim of this study was to define the characteristics of IBD, the trends and phenotype among IBD patients in Romania. Material and methods: We conducted a prospective study over a period of 12 years, from 2006 to 2017. All patients diagnosed with IBD on clinical, radiological, endoscopic and histological features were included. We divided the country into eight regions: west (W), north-east (NE), north-west (NW), south-east (SE), south-west (SW), south (S), central (C) and Bucharest-Ilfov (B), and data were analyzed accordingly. Results: A total of 2724 patients were included in this database, but only 2248 were included in the final analysis, with all data available. Of the 2248 patients, 935 were Crohn&rsquo, s disease (CD), 1263 were ulcerative colitis (UC) and 50 were IBD-undetermined. In UC phenotypes we observed more frequent left-sided colitis (50.5%, p &lt, 0.0001), and in CD phenotype we observed more frequent colonic and ileo-colonic localization (37.8% and 37.6%, p &lt, 0.0001). The region with the most IBD cases was NE (25.1%) and with the least IBD cases was SW (4.9%). UC was found more frequently in NE (32%), while CD was found more frequently in Bucharest (28.6%). Conclusions: In Romania, ulcerative colitis is more frequent than CD. UC is predominant in the northern part of Romania, while CD has become predominant in the southern part of the country. IBD occurs more in the male population, and in urban and industrialized areas. There are differences between the regions in Romania regarding IBD phenotypes, gender distributions, age distribution, treatment, smoking status and complications.

Background & Aims: Prevalence of malnutrition in inflammatory bowel diseases (IBD) varies between 16% and 75%. Data on the nutritional status at initial diagnosis of ulcerative colitis (UC) or Crohn’s Disease (CD) are scarce. It is believed that more than 50% of IBD patients suffer significant weight loss prior to diagnosis. The aims of our study were to assess malnutrition in patients recently diagnosed with IBD and to determine its predictive factors. Methods: We retrospectively included 625 IBD patients registered in the Romanian “IBD Prospect” database between January 2006 and July 2017. All patients were diagnosed within 6 months prior to registration. We defined malnutrition as weight loss of more than 5% of the initial weight during the 3 months prior to registration. Results: There were 361 new cases of UC, 241 CD and 23 cases of unclassified IBD. There was a slight male predominance (M/F=1.2). Prevalence of overall malnutrition was 36.3%. It was significantly more frequent in CD than in UC patients (41.1% vs. 32.4%, p=0.031). In multivariate analysis, malnutrition in UC patients was associated with male gender (p=0.001), more severe disease (p

Background Inflammatory bowel diseases (IBD) are chronic conditions that require multiple endoscopic and imaging assessments. Recent guidelines recommend bowel ultrasonography (BUS) as a complimentary imaging technique to assess transmural and extraintestinal lesions. The aim of the present study was to evaluate the accuracy of BUS in predicting the need to step-up therapy in IBD patients. Methods 117 IBD patients were included in the study (28 diagnosed with ulcerative colitis, 89 with Crohn’s disease). Following bowel ultrasound features bowel ultrasound features have been investigated: bowel wall thickness, loss of wall stratification, presence of bowel wall Doppler signal, the presence of hyperechoic spots inside the bowel wall, the irregularity of the external layer of the wall, the presence of creeping fat (mesenteric hypertrophy), the presence of visible lymph nodes. Patients were followed up for the next 6 months and data regarding their therapy was noted. Results During follow-up, therapeutic step-up, or biological treatment intensification (study outcome) were considered in 49.5% of cases in our study group. In a univariate analysis all the studied bowel ultrasound features but not the disease phenotype were significantly associated with the outcome. In the multivariate analysis only mean bowel wall thickness ( Conclusion As the “treat to target concept” is the currently accepted novel treatment paradigm, incorporating BUS in IBD patients monitoring (BU score) provides an easy-to-use and readily available tool to stratify patients in need for therapeutic intensification.

Acute on chronic liver failure (ACLF) is a dynamic syndrome, but frequently associated with a high 1 month mortality rate. This is the first study applying the new European Association for the Study of the Liver- chronic liver failure consortium criteria to explore mortality on the waiting list (WL) and early after liver transplantation (LT) in a cohort of Romanian cirrhotic patients that improved or recovered after an episode of ACLF. To assess frequency and waitlist mortality for different grades of ACLF. An observational study was conducted; 257 patients with liver cirrhosis included on the WL between 2015 and 2017 were analyzed. The cumulative incidence of waitlist mortality or removal was calculated for combination of competing events using multivariable competing risks regression. ACLF-1 occurred in 12.07%, ACLF-2 in 7.39% and ACLF-3 in 8.56% of patients. Median Model for End Stage Liver Diseases (MELD) score at the moment of ACLF was 29. The main event while on the WL was death, followed by ACLF; patients with ACLF-3 had a significantly greater subhazard ratio for mortality of 2.25 (1.55–3.26) compared to patients with ACLF-1 or 2. LT proved to be associated with a significantly lower risk of death on the WL at 6 months after inclusion. One and 12 months post-transplant survival of patients with or without ACLF was similar (P = .77). Occurrence of an ACLF episode while on the WL is associated with a significantly high mortality rate, as well as MELD score at inclusion on the WL, renal and liver failure, presence of hepatic encephalopathy. Overall patient short and long term survival after LT is similar to non-ACLF patients in good selected cases.

The epidemiology of inflammatory bowel disease [IBD] in Eastern Europe is poorly understood, particularly with regard to diagnostic delay. Here we investigated the factors leading to delayed diagnosis and the effect of the delay on several disease progression and outcome measures.A total of 1196 IBD cases [682 ulcerative colitis [UC], 478 Crohn's disease [CD], 36 indeterminate colitis] from the Romanian national registry IBDPROSPECT were reviewed. Standard clinical and demographic factors were evaluated as predictors of a long diagnostic delay in both CD and UC. Diagnostic delay was subsequently evaluated as a potential risk factor for bowel stenoses, bowel fistulas, perianal fistulas, perianal surgery, and intestinal surgery in CD patients.The median diagnostic delay was significantly longer in CD [5 months] than in UC [1 month] patients [p0.001]. Compared with 5 months for UC patients, 75% of CD patients were diagnosed within 18 months of symptom onset. In CD patients, extra-ileal location was a protective factor (odds ratio [OR], 0.5; p = 0.03), whereas being an active smoker [OR, 2.09; p = 0.01] and symptom onset during summer [OR, 3.35; p0.001] were independent risk factors for a long diagnostic delay [18 months]. In UC patients, an age40 years was a protective factor [OR, 0.68; p = 0.04] for a long delay. Regarding outcomes, a long diagnostic delay in CD patients positively correlated with bowel stenoses [OR, 3.38; p0.01] and any IBD-related surgery [OR, 1.95; p = 0.03] and had a positive trend for intestinal fistulas [OR, 2.64; p = 0.08] and perianal fistulas [OR, 2.9; p = 0.07]. Disease duration since diagnosis positively correlated with bowel stenoses [OR, 1.04; p = 0.04], any IBD-related surgery [OR, 1.04; p = 0.02], and intestinal surgery [OR, 1.07; p0.01].A long diagnostic delay in IBD correlates with an increased frequency of bowel stenoses and need for IBD-related surgery.

Background and aims Cytokines and their receptors play a critical role in the pathogenesis of the inflammatory bowel disease (IBD). The aim of this study was to investigate the expression profiles of inflammatory genes in inflamed and non-inflamed colonic tissue samples in patients with Crohn's disease (CD) and ulcerative colitis (UC), and to identify molecular signatures for different IBD phenotypes. Methods Seventy-one patients diagnosed with IBD (38 CD, 33 UC) and 15 non-IBD controls have been included in the study. For each patient, biopsy samples were obtained during colonoscopy from inflamed (L) and healthy (N) mucosa. We investigated by commercially available reverse-transcriptase multiplex ligation-dependent probe amplification (RT-MLPA) kit the mRNA expression of a set of 40 genes involved in inflammation: cytokines, chemokines, receptors, signal transduction molecules and transcription factors. Results In L biopsies from patients with CD, higher expression levels were found for IL-4 (p = 0.009) and IL-12p35 (p = 0.0005), whereas in L biopsy samples from patients with UC higher expression levels were found for IL-8 (p = 0.03), chemokines SCYA3 (p = 0.05), SCYA4 (p = 0.01) and glutathione S-transferase P1 (p = 0.01). In N biopsies of patients with CD higher expression levels were found for IL-1R (p = 0.01) and IL-12p35 (p = 0.007), whereas in N biopsies of patients with UC higher expression levels were found for IL-15 (p = 0.009) and SCYA8 (p = 0.001). The logistic regression analysis has indicated that low expression levels of IL-2 and IL-10, together with higher ASCA IgG titers were independently associated with penetrating/stricturing CD. Conclusions RT-MLPA is a sensitive and effective method for the evaluation of the profiles of inflammatory genes in IBD, with potential future applications for diagnosis, phenotypic stratification and targeted therapy.

We present the case of a 63-year-old man that was admitted for melena and severe anemia. Upper GI endoscopy and colonoscopy failed to identify the lesion responsible for bleeding, and enteroCT scan was also non-contributive to the diagnosis. Capsule endoscopy indicated possible jejunal bleeding but could not indicate the source of bleeding, recommending anterograde enteroscopy. Single balloon enteroscopy identified a 2 cm submucosal tumour in the distal part of the jejunum, with a macroscopic appearance suggesting a gastrointestinal stromal tumour (GIST). The tumor location was marked using SPOT tattoo and subsequently easily identified by the surgeon and resected via minimally invasive laparoscopic-assisted approach. Histological and immunohistochemical analysis indicated a low risk GIST.The unusual small size of the GIST as a modality of presentation, with digestive bleeding and anemia and the ability to use VCE/enteroscopy to identify and mark the lesion prior to minimally invasive surgery, represent the particularities of the presented case. Abbreviations: CA19-9: cancer antigen 19-9; CEA: carcinoembryonic antigen; GI: gastrointestinal; GIST: gastrointestinal stromal tumor; Hb: hemoglobin; HPF: high power field; MCH: mean corpuscular hemoglobin; MCV: mean corpuscular volume; VCE: videocapsule endoscopy.

Background: Pancreatic cancer (PC) is usually diagnosed in the 7th decade, but cases diagnosed in younger patients are associated with a greater disease burden, through the potential years of life lost. The aim of our study was to compare the differences in risk factors, clinical presentation and treatment options between patients diagnosed with pancreatic adenocarcinoma below 45 years of age (very early onset pancreatic adenocarcinoma - VEOPC), and those diagnosed over 45 years. Methods: A retrospective study has been conducted by registering in standardized Excel Worksheets all PC cases diagnosed in our tertiary referral center between 01.01.2015 and 31.12.2017. Only patients with a documented diagnosis of pancreatic adenocarcinoma (PDAC) were included in the statistical analysis that has been conducted using the NCSS v9 Statistical Software package. Categorical data have been compared using Chi2 test or Fisher Exact as appropriate, with a statistical significance p value 0.05. Results: There were 296 patients diagnosed with pancreatic solid tumors during the study period, 183 cases with documented histology: 80.87% PDAC, 17.5% neuroendocrine tumors, 2 cases of LMNH and 1 MANEC tumor. In our study group there were 24 patients (16.22%) with VEOPC. Family history of pancreatic neoplasia (33.3% vs 1.03%, p=0.0004) and alcohol consumption (42.86% vs 5.41%, p=0.01) were significantly more prevalent in young patients. Pain, as primary symptom, was reported at higher rates in patients with VEOPC (60% vs 22.94%, p=0.006). Tumors were more frequently located in the head of the pancreas in younger patients (56.52%) and in the body of the pancreas in older patients (52.07%, p=0.02). There was no significant difference in therapy or death rate during follow-up period between the two study groups, although patients diagnosed under 45 years were more frequently subjected to a radical resection (33.3% vs 22.69%). Conclusions: Our study has identified alcohol consumption and family history of pancreatic neoplasia as risk factors for VEOPC. Pain is the primary symptom at diagnosis in young patients with PDAC. In our cohort, therapeutic options do not differ significantly in PDAC patients with age of onset.

OBJECTIVES To evaluate the frequency of cholestatic pattern in patients with autoimmune hepatitis (AIH) and to identify predictive factors associated with the development of the overlap syndrome. METHODS Eighty-two consecutive patients diagnosed with AIH at the referral centre between January 1998 and June 2002 were included in the study. The new scoring system modified by the International Autoimmune Hepatitis Group was used to classify patients as definite/probable. Overlap syndrome was considered when the patient had clinical, serological and histological characteristics of two conditions: AIH and primary biliary cirrhosis (PBC) or AIH and primary sclerosing cholangitis (PSC). RESULTS From the 82 AIH patients (76 female and six male), 84.1% presented definite AIH (> 15 points) and 15.9% probable AIH (10 - 15 points). The frequency of the overlap syndrome was 20%: 13% with PBC and 7% with PSC. In the univariate analysis the overlap syndrome was associated with male gender (P = 0.01), age < 35 years (P < 0.0001), histopathological aspect of cholestasis (P < 0.0001), suboptimal response to treatment (P < 0.0001) and probable AIH (P < 0.0001). Age < 35 years, probable AIH and the absence of anti-nuclear antibody (ANA) have been identified as independent indicators of the overlap diagnosis by the logistic regression analysis. CONCLUSION Patients with overlap syndrome between AIH and primary cholestatic liver disease are frequently diagnosed in clinical practice, representing 20% of AIH cases in our study. The independent predictive factors associated with the diagnosis of overlap syndrome are young age, ANA(-) profile, and probable diagnosis according with the scoring system for AIH.