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The purpose of this article is to investigate and analyze the practices of scientific management within the County Departments of Sports and Youth (CDSY) in Romania. Conducted through a comprehensive research endeavor spanning from January to June 2022, the study utilized a standardized questionnaire as its primary instrument for data collection, distributed among CDSY directors. A notable finding from the study indicates that a significant proportion of respondents (44.9%) perceive notable disparities in the normative-functional elements governing the National Sports System in Romania compared to international standards. Moreover, the majority (51%) consistently adhere to regulatory acts, while a substantial portion (69.4%) underscore the importance of strict adherence to internal regulations in strategy formulation. Furthermore, an overwhelming majority (88.9%) acknowledge the substantial influence of available resources on strategy development, with collaboration with authorities primarily occurring through direct communication channels. Respondents prioritize multiple objectives (44.9%), affirm the necessity of various competencies (53.1%), and identify a lack of human and financial resources (59.2%) as the most significant obstacle. Notable achievements highlighted in the study include the improvement of the county's sports performance (53.1%). Respondents also believe that setting clear and realistic objectives (38.8%) is pivotal to enhancing CDSY management, while considerations in formulating strategies emphasize trends in the sports domain (42.9%) and the specific needs of the local sports community (42.9%). Overall, this research contributes to the understanding and promotion of more efficient practices in managing sports and youth departments within Romania's counties. [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]

An editorial discusses the readiness of Romania's Colorectal Cancer Screening Program (ROCCAS) for national implementation. It highlight the global impact of colorectal cancer (CRC) and the significance of screening programs. It emphasizes key aspects, including the involvement of family doctors, program objectives, and performance indicators, showcasing the potential positive impact on CRC mortality.

Background. Endoscopic ultrasound (EUS) in association with fine needle aspiration (FNA) it is considered to be the standard of pancreatic mass lesions diagnosis. Our aim was to determine which ultrasound features, including a particular hypoechoic rim aspect can predict a pancreatic neuroendocrine tumor (pNET) diagnosis. Methods. The EUS examinations performed for solid pancreatic lesions from 2015 to 2019 in a Tertiary Gastroenterology Center were evaluated in a prospective study. There were 175 cases analyzed, out of which pNET diagnosis was established by FNA in n= 19 (10.8%). Mean age of patients with pNETs was 56.1 ± 10.3 years, significantly lower than all cases in the study group and 52.7% of which were females. We studied the following EUS characteristics by univariate and multivariate analysis: well defined margins, hypoechoic EUS aspect, homogeneous pattern, the presence of internal vascularization, stiff elastographic appearance, the presence of multiple lesions, the internalization of large vessels, Wirsung duct dilation and the presence of a hypoechoic rim delimiting the interior margin of the lesion. Results. The following EUS features were significantly associated with EUS diagnosis of pNET: well defined margins (63.1% vs 35.7% p=0.02), homogeneous pattern (36.8% vs 16.9%, p=0.03), the presence of internal vascularisation (63.1% vs 24.3%, p=0.0004), blue on elastography (89.4% vs 64.2%, p=0.03) and the presence of a hypoechoic rim (47.3% vs 2.5%, P< 0.0001). In the multivariate logistic regression analysis only the presence of a hypoechoic rim was independently associated with the pNET diagnosis (p< 0.0001). Conclusions. EUS appearance can suggest the diagnosis of a pNET. The presence of a hypoechoic rim delimiting the interior margin of the lesion is an independent predictor of pNET diagnosis. [ABSTRACT FROM AUTHOR]

It is imperative to comprehend the determinants shaping entrepreneurial intent, especially during pivotal junctures when individuals are navigating career decisions. This research endeavors to scrutinize the entrepreneurial intent of university students, with a specific focus on the sports domain, and examine the potential impact of their involvement in sports activities on said entrepreneurial intent. The participants comprised 415 students from the academic sports domain in four cities in Romania (Pitesti, Alba-Iulia, Cluj-Napoca, and Sibiu). They were administered a 35-item questionnaire and subsequently categorized into four groups based on their sports background: individuals and team sports participants with a competitive history, amateur athletes, and non-practitioners. The questionnaire demonstrated strong internal consistency (Cronbach's alpha coefficient = 0.755). A test of homogeneity across criteria such as competitive sports involvement, type of competitive sports, and engagement in amateur sports revealed significant differences in five out of 45 comparisons. Furthermore, this study employs an explanatory approach to elucidate the distinctions among athletes, amateur, and non-athlete students in academic sports programs regarding: comfort and security in workplace stability, embracing risk-taking for gains, proactive problem-solving, expectations from superiors, work ethic and goal orientation, workload and productivity relationship, task completion and challenge acceptance, work avoidance and problem management, work-life balance prioritization, openness to personal development, parallels between sports and business strategies, taking initiative and responsibility, entrepreneurial determination, comfort zone preference and adaptation after sports career. [ABSTRACT FROM AUTHOR]

Introduction. It is well known that portal vein thrombosis (PVT) can accelerate liver decompensation, reducing overall survival. In the literature, the topic whether PVT is a risk (1) factor for variceal bleeding or it influences the effectiveness of variceal band ligation (VBL) remains of great interest The aim of this study was to assess if VBL is a potential risk factor for PVT development. An observational and retrospective study was conducted in a single tertiary center from 2010 to 2021 and included data from 285 patients with liver cirrhosis. Results. Of the 285 patients, gender distribution described 47.32% female (n =135) and 52.8% male (n =150) with a mean age of 55 years (range =23-79). The average MELD score was 12.5 (range 7-27). Of the total number of patients, 48.8% (n=139) had previous VBL: 20% (n=57) underwent primary prophylactic VBL and 34.7% (n=99) underwent secondary prophylaxis. Thus, 285 VBL procedures had been performed and the average number of VBL session was 2 (range 1-10) The mean time follow up was 92.55 months (range 22-230. During the follow up period PVT was diagnosed in 41.4% of patients (n =118) of which 67.77% (n =80) had at least one previous session of VBL: 33% of patients (n =39) had performed primary prophylaxis and 34.74% (n =41) secondary. A logistic regression was conducted to assess if VBL (primary and/or secondary prophylaxis) are risk factors for PVT development. The model was significant for primary prophylaxis (p =0.002, OR 3.28, CI 1.53-7.02) resulting that the risk of PVT is increasing around 3 times after primary prophylactic VBL. Conclusion. Our study showed a certain predisposition for cirrhotic patients to develop PVT after VBL performed as primary prophylaxis thus raising the question: does VBL impact the occurrence of PVT in cirrhotic patients? Furthermore, to our knowledge, this is the first study in the literature that focuses on this topic. More studies should be performed to evaluate and describe the relationship between VBL and the risk of PVT. [ABSTRACT FROM AUTHOR]

Purpose: Idiopathic clubfoot affects approximately 1/1000 alive-born infants, of whom 80–91% are born in low- or middle-income countries (LMICs). This retrospective study aimed to evaluate the morphological, functional, and social outcomes in patients with neglected clubfoot in rural Bangladesh, after receiving surgical treatment. Methods: Patients received a posteromedial release (PMR) with or without an additional soft tissue intervention (group 1), a PMR with an additional bony intervention (group 2), or a triple arthrodesis (group 3) according to our surgical algorithm. Patients were followed until two year post-intervention. Evaluation was done using a modified International Clubfoot Study Group Outcome evaluation score and the Laaveg-Ponseti score. Results: Twenty-two patients with 32 neglected clubfeet (ages 2–24 years) received surgical treatment. Nineteen patients with 29 clubfeet attended follow-up. At two year follow-up an excellent, good, or fair Laaveg-Ponseti score was obtained in 81% (group 1), 80% (group 2), and 0% (group 3) of the patients (p value 0.0038). Age at intervention is inversely correlated with the Laaveg-Ponseti score at two year follow-up (p < 0.0001). All patients attended school or work and were able to wear normal shoes. Conclusion: Our treatment algorithm is in line with other surgical algorithms used in LMICs. Our data reconfirms that excellent results can be obtained with a PMR regardless of age. Our algorithm follows a pragmatic approach that takes into account the reality on the ground in many LMICs. Good functional outcomes can be achieved with PMR for neglected clubfoot. Further research is needed to investigate the possible role of triple arthrodesis. [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]

Circulating cell-free DNA (ccfDNA) quantity correlates with the clinical characteristics and prognosis of various cancer types. We investigated whether ccfDNA levels and the neutrophil-to-lymphocyte ratio (NLR) have prognostic value in patients with pancreatic ductal adenocarcinoma (PDAC). Peripheral blood was collected from 82 patients with PDAC prior to any diagnostic procedure or the administration of chemotherapy. Plasma DNA was isolated, and ccfDNA concentration and NLR were determined. We found that ccfDNA levels were correlated with age and tumor burden. Moreover, higher values of NLR (≥3.31) were linked with worse overall survival (OS) (4 vs. 10 months; log rank p = 0.011), and an elevated ccfDNA concentration (≥25.79 ng/mL) was strongly associated with shorter OS (4 vs. 8 months; log rank p = 0.009). According to the results of the multivariable Cox regression analysis, the baseline concentration of ccfDNA was an independent prognostic factor for OS (HR 0.45, 95% CI 0.21–0.97, p = 0.041). Furthermore, the combination of ccfDNA levels with NLR greatly enhanced the prognostic accuracy of PDAC patients. Our study demonstrates that ccfDNA concentration and NLR are independent predictors of survival in PDAC. Subsequent studies should validate this combination as a prognostic indicator in PDAC patients and assess its utility for guiding therapeutic decisions. [ABSTRACT FROM AUTHOR]

Background & Aims: Non‐selective β‐blockers (NSBBs) and endoscopic variceal‐ligation (EVL) have similar efficacy preventing first variceal bleeding. Compensated and decompensated cirrhosis are markedly different stages, which may impact treatment outcomes. We aimed to assess the efficacy of NSBBs vs EVL on survival in patients with high‐risk varices without previous bleeding, stratifying risk according to compensated/decompensated stage of cirrhosis. Methods: By systematic review, we identified RCTs comparing NSBBs vs EVL, in monotherapy or combined, for primary bleeding prevention. We performed a competing‐risk, time‐to‐event meta‐analysis, using individual patient data (IPD) obtained from principal investigators of RCTs. Analyses were stratified according to previous decompensation of cirrhosis. Results: Of 25 RCTs eligible, 14 failed to provide IPD and 11 were included, comprising 1400 patients (656 compensated, 744 decompensated), treated with NSBBs (N = 625), EVL (N = 546) or NSBB+EVL (N = 229). Baseline characteristics were similar between groups. Overall, mortality risk was similar with EVL vs. NSBBs (subdistribution hazard‐ratio (sHR) = 1.05, 95% CI = 0.75–1.49) and with EVL + NSBBs vs either monotherapy, with low heterogeneity (I2 = 28.7%). In compensated patients, mortality risk was higher with EVL vs NSBBs (sHR = 1.76, 95% CI = 1.11–2.77) and not significantly lower with NSBBs+EVL vs NSBBs, without heterogeneity (I2 = 0%). In decompensated patients, mortality risk was similar with EVL vs. NSBBs and with NSBBs+EVL vs. either monotherapy. Conclusions: In patients with compensated cirrhosis and high‐risk varices on primary prophylaxis, NSBBs significantly improved survival vs EVL, with no additional benefit noted adding EVL to NSBBs. In decompensated patients, survival was similar with both therapies. The study suggests that NSBBs are preferable when advising preventive therapy in compensated patients. [ABSTRACT FROM AUTHOR]

Introduction. Crohn's disease (CD) and ulcerative colitis (UC), can resemble similarities regarding endoscopic/histologic aspects, which carry different outcomes. The definitive diagnosis of IBD requires corroboration of multiple datas, upper and lower endoscopy playing an important role for the positive diagnostic and for excluding other causes of diarrhea. Study objective: This work is a single-center study with retrospective recruitment of patients with first diagnosis of IBD and its primary objective is to analyze whether or not there is a relationship between the macroscopic diagnosis and the histopathological one. As secondary objectives we analized epidemiological data, symptoms, macroscopic appearence of the lessions and the existence of microscopic lessions and we calculated histopathological scores (GHAS for CD and Geboes for UC). Materials and Methods. A retrospective recruitment of patients newly diagnosed with IBD has been made, within 4 years. 174 patients were eligible and were distributed into two groups: 80 patients with exclusive colonic CD and 94 patients with pancolitis. Patients with ileal involvement, fistulizing pattern, or who were already diagnosticated and treated were excluded. Results. We had a slightly male preponderance (52.9% versus 47.1%) with a mean age of disease onset of 38.0 years; we had 68.7% patients with CD inflammatory pattern, respectively 31.3% with stenosing one. Most of the patients had moderate disease (34 -CD and 57-UC). Most commonly reported macroscopic appearance was erythema and oedema in both groups: 76.4% (CD) and 87.4% (UC). In terms of histological severity, severe forms (translated by Geboes score >3.1 and GHAS > 10) are overwhelmingly found in both groups. Conclusions. The concordance between the macroscopic appearance reported by the endoscopist and the microscopic appearance concluded by the pathologist, correlated positively with the degree of chronic inflammation for patients with UC, but we did not obtain similar results for those with CD, partialy reflecting the discontinuous nature of the lessions. The results of the correlation between Mayo score and Geboes score demonstrated that any increase in the degree of chronic inflammation, architectural changes, presence of eosinophils or neutrophils in the lamina propria, or erosions/ulcerations were associated with an increase in Mayo score. Concerning a possible correlation between the severity of CD and histopathological appearance, we had a striking observation, namely that no statistically significant association between predictors and the degree of severity of CD was evident. In conclusion, we hypothesized that a possible influence of histopathological lesions on disease severity is small. [ABSTRACT FROM AUTHOR]

Introduction. Acute pancreatitis (AP) is among the most common causes of emergency admissions in gastroenterology departments. Although AP etiology comprises mainly gallstones, alcohol abuse, and hyperlipidemia, there is a strong, bidirectional association between AP and pancreatic cancer (PC). Case presentation. We present the case of a 76-year-old woman, smoker (15 pack-years), nondrinker, without relevant personal/family medical history, admitted in another unit for intense epigastric pain irradiated to the back, nausea and vomiting for 10 days prior to hospitalization. She also reported unintentional weight loss - 10 kilograms in six months. At that time - there were no remarkable clinical findings, the blood tests showed high amylase (2 times the upper normal limit(2xULN)), moderate inflammation, mild hyperglycemia, normal liver function tests, and triglycerides. She was diagnosed with acute pancreatitis (AP). The supportive treatment (hydration, pain killers) lead to symptoms decrease. One week afterward a contrast enhanced abdominal CT (CECT) scan was performed revealing a pancreatic head mass (55 mm), invading the duodenum, lesser gastric curvature, in contact with the superior mesenteric artery (SMA), also common bile duct and Wirsung duct dilation and small fluid pericefalic collections. She was referred to our hospital for further investigations. At admission (one month after symptoms onset) the pain persisted, the blood test showed - high - amylase (2xUN) and lipase (5xULN), cholestasis (GGT-5xUNL, ALP - 1.5xUNL, normal BB), moderate inflammation, hyposideremia (22ug/dL). Endoscopic ultrasound (EUS) was performed describing a voluminous pancreatic head cystic lesion compressing the gastric wall - drainage was considered unsafe. She was further referred to abdominal MRI performed 3 months after disease onset that showed a locally advanced pancreatic head tumor, complete regression of the pseudocyst. The patient became jaundiced (total BB of 7 mg/dL) and continued to lose weight. EUS tissue acquisition (EUS-TA) was performed. The pathology results established the diagnosis of high-grade pancreatic adenocarcinoma. Discussion. This was a case of AP caused by PC diagnosed at 2 months after AP onset by EUS-TA after AP remission. The tumor had otherwise a typical course with weight loss, abdominal pain, and jaundice A biliary stent will be placed and chemotherapy will be started. Conclusion: Although rare clinicians must be aware of the PC etiology of AP - especially in older patients, with presumably idiopathic AP etiology, weight loss, and concomitant new-onset diabetes. To this end, a follow-up CECT must be performed during the first year after AP in selected cases. [ABSTRACT FROM AUTHOR]

Simple Summary: The available chemotherapeutic regimens for metastatic pancreatic ductal adenocarcinoma (mPDAC) in Romania include FOLFIRINOX (FFX), gemcitabine-based regimens (GB), and gemcitabine monotherapy (Gem). The purpose of our study was to compare the efficacy of FFX, GB, and Gem in patients with mPDAC in real-world scenarios. Our research revealed that the overall survival (OS) of patients receiving FFX or GB was comparable, twice as long as that of patients receiving Gem, and the progression-free survival (PFS) was highest for patients receiving FFX as first-line chemotherapy (L1). Male gender, Eastern Cooperative Oncology Group Performance (ECOG-PS) 0/1, the FFX regimen, and neutrophil-to-lymphocyte ratio (NLR) > 4.15 were all independently linked to a longer OS. L1 with FFX improved both OS and PFS for second-line chemotherapy (L2). Purpose: To assess the efficacy of FOLFIRINOX(FFX), gemcitabine-based regimens (GB), and gemcitabine monotherapy (Gem) in patients with metastatic pancreatic ductal adenocarcinoma (mPDAC). Methods: This is a retrospective study that included 83 patients with mPDAC treated with first-line chemotherapy (L1) with either FFX, GB or Gem between 2015 and 2017. Progression-free survival (PFS) for L1 and second-line chemotherapy (L2) (PFS-L1 and PFS-L2) and overall survival (OS) were estimated using the Kaplan–Meier method. Results: Median PFS-L1 for FFX, GB and Gem groups was 9 months (95% (Confidence Interval) CI 2.76–15.24), 5 months (95%CI 3.44–6.56), and 5 months (95%CI 3.76–6.24), respectively (p = 0.04). OS was 14 months (95%CI 11.16–16.85), 12 months (95%CI: 9.44–11.56), and 7 months (95%CI: 5.7–8.3) for patients treated with FFX, GB, and Gem, respectively (p = 0.0001). ECOG-PS (0/1) (Hazard Ratio (HR) 6.74, p = 0.002), age > 70 years (HR 0.25, p = 0.04), body tumors (HR 2.8, p = 0.048), CA19–9 > 39 U/mL (HR 0.26, p = 0.02), and neutrophil-to-lymphocyte ratio (NLR) > 4.15 (HR 6.76, p = 0.001) were independent prognostic factors for PFS-L1. Male gender (HR 3.02, p = 0.026), ECOG-PS (0/1) (HR 4.21, p = 0.003), L1 with FFX (HR 0.255, p = 0.007), and NLR > 4.15 (HR 2.65, p = 0.04) were independent prognostic factors of OS. PFS-L2 (HR 6.91, p = 0.013) and OS-L2 (HR 6.95, p = 0.037) were significantly higher in patients first treated with FFX. Conclusions: The OS of patients who receive FFX or GB is comparable. The best PFS-L1 belongs to the FFX group. Male gender, ECOG-PS 0/1, the FFX regimen, and NLR > 4.15 were independent predictors of OS. PFS-L2 and OS-L2 were favorably impacted by L1 with FFX. [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]

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]

Background & 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 cases). 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 (p<0.0001), and the presence of the bowel wall Doppler signal (p=0.007) were independent predictors of the main outcome. For the subgroup analyses: mean BWT (p=0.0001) and the presence of the bowel wall Doppler signal (p=0.01) were independent predictors for immediate treatment intensification (active disease at baseline) and mean BWT (p=0.0003) and the lack of bowel wall stratification (p=0.05) were independent predictors for the need of subsequent therapeutic optimization. Logistic regression prediction models and prediction scores (BU score) had the best AUROC values (>0.91) 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. [ABSTRACT FROM AUTHOR]

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

Pancreatic ductal adenocarcinoma (PDAC) is among the most lethal cancers. Its poor prognosis is predominantly due to the fact that most patients remain asymptomatic until the disease reaches an advanced stage, alongside the lack of early markers and screening strategies. A better understanding of PDAC risk factors is essential for the identification of groups at high risk in the population. Genome-wide association studies (GWAS) have been a powerful tool for detecting genetic variants associated with complex traits, including pancreatic cancer. By exploiting functional and GWAS data, we investigated the associations between polymorphisms affecting gene function in the pancreas (expression quantitative trait loci, eQTLs) and PDAC risk. In a two-phase approach, we analysed 13 713 PDAC cases and 43 784 controls and identified a genome-wide significant association between the A allele of the rs2035875 polymorphism and increased PDAC risk (P = 7.14 × 10−10). This allele is known to be associated with increased expression in the pancreas of the keratin genes KRT8 and KRT18 , whose increased levels have been reported to correlate with various tumour cell characteristics. Additionally, the A allele of the rs789744 variant was associated with decreased risk of developing PDAC (P = 3.56 × 10–6). This single nucleotide polymorphism is situated in the SRGAP1 gene and the A allele is associated with higher expression of the gene, which in turn inactivates the cyclin-dependent protein 42 (CDC42) gene expression, thus decreasing the risk of PDAC. In conclusion, we present here a functional-based novel PDAC risk locus and an additional strong candidate supported by significant associations and plausible biological mechanisms. [ABSTRACT FROM AUTHOR]

Introduction. Obesity, lack of physical activity and diet have been inconsistently associated with pancreatic cancer. Aim. To evaluate the prevalence of overweight, body weight change trends, diet and physical activity level in pancreatic cancer patients diagnosed between 01.2018-02.2023. Methods. Prospective observational study that included patients diagnosed with pancreatic adenocarcinoma who were interviewed about dietary habits and weight changes, and physical activity over time. Results. A total of 186 patients with pancreatic adenocarcinoma were included. Regarding weight changes, it was observed that 56% of patients were under or normal weight at diagnosis, while a BMI below 25 was observed at one year and 5 years before only in 19.35%, respectively 12.9%. Excluding the data 5 years before diagnosis, the overweight and obesity prevalence between 20-29 years old was 43.54% respectively 11%, at 30-39 years old 43.54% respectively 25.8%, at 40-49 years old 22% respectively 45,6%, and at 50-59 years old 34% respectively 52.3%. Over 50 % of patients led a sedentary life. Regarding diet more than 75% of patients consumed red meat, dairy products, bread and bakery products, fruits and vegetables regularly more than 5 times a week. The consumption of fish and nut products was generally much less frequent, maximum 2 times a week in over 80% of cases. Less than half of the patients (47%) confirmed alcohol consumption, mostly occasionally, only 17% reported drinking more than 5 times a week. The favorite alcoholic drink was liquor, followed by wine, generally homemade. Conclusions. Most of the patients in the study were obese throughout their lives, but there was a weight loss starting 5 years before diagnosis, more severe in the last year. This can be explained by the advanced degree of the disease at diagnosis associated with a possible paraneoplastic hyperanabolic syndrome, the majority not complaining of loss of appetite or early satiety in the last year. Diet studies have suggested a protective effect against pancreatic cancer of the Mediterranean diet and regular consumption of nuts, even if in small quantities. This can also be confirmed by the patients included in this study whose diet does not respect these principles. Alcohol consumption does not seem to increase the risk of pancreatic neoplasm. This has also been observed in numerous studies with inconsistent results, and can also be determined by a declarative reduced consumption, due to the stigma associated with high consumption. [ABSTRACT FROM AUTHOR]

Introduction. In the last decade, bariatric surgery has proven to be the only effective method for weight loss (WL) in patients with morbid obesity. Objective. To determine the factors that influence optimal WL after sleeve gastrectomy in patients with morbid obesity. Material and method. 72 patients with BMI >40 kg/m2 or BMI 35-39.9 kg/m2 with severe comorbidities were included in the study. The patients were evaluated clinical, biochemical, immunological, imaging and histological preoperative and postoperative (on average 8.7 months after the surgical intervention). WL were assessed by calculated the percentage of excess body mass index loss (%EBMIL) using the following formulas %EBMIL=(BMI1-BMI2) / (BMI1-25) x100; Optimal treatment response was considered a decrease in %EBMIL >50 Results. The patient had a mean age of 44.78±10.5 years, an average BMI and preoperative waist of 47.05 kg/m2 (between 33.3 and 70.1), respectively 130 cm (between 90 and 180cm). The results of our study showed a mean decrease in %EBMIL of 69.9 ± 27.6 (14.6-144.47), the value that shows an optimal response of postoperative weight loss. Using the univariate analysis we noted a negative correlation between % EBMIL and both the age and initial BMI of the patients (r=-0.438, p<0.01, r2=0.19). Patients with optimal WL have statistically significantly lower preoperative values of FG (U= 95.5, z=-2.25, p<0.05), TNFα (U=53, z=-2.5, p<0.05) and IL-6 (U=79, z=-2.3, p<0.05) compared to patients without clinical response (%EBMIL<50%). A negative correlation between %EBMIL and the presence of NASH was also found. Patients with preoperative NASH had a significantly lower %EBMIL than those with simple steatosis (U=56, z=-2.2, p<0.05). Conclusions. Sleeve gastrectomy was an effective bariatric surgery to treat obesity. Preoperative BMI, excess weight, age, TNF α, IL-6 and the presence of diabetes and steatohepatitis were predictive factors for optimal weight loss in patients with morbid obesity after sleeve gastrectomy. [ABSTRACT FROM AUTHOR]

Background and aim. In spite of prolonged disease remission of IBD patients, induced by the new biological molecules, a significant number of them suffer from persistent debilitating symptoms with major impact on the quality of life. Frequently, these symptoms are due to post-inflammatory motility changes and misinterpreted as functional disorders. Our aim is to identify and characterize the anorectal motility dysfunction in IBD patients. Method. We are conducting an ongoing prospective study started in August 2019, which includes the IBD patients admitted in a Tertiary Gastroenterology Centre in Bucharest, with specific symptoms (anorectal pain, incontinence, difficult defecation). We perform high resolution anorectal manometry using Sandhill Scientific systems, the parameters being analysed using InSIGHT software. The manometric testing comprise measurements of anorectal pressure at rest, during squeeze, simulated evacuation, rectoanal inhibitory reflex (RAIR) and rectal sensory testing, in compliance with International Anorectal Physiology Working Group protocol. Results. We studied 21 patients (12 patients with Ulcerative Colitis and 9 patients with Crohn's Disease, 15 females and 6 males, mean age 40 (±11.43) years. Only 23.1% (5 patients) had rectal active involvement. Symptoms were reported by 81.0% (17) patients: pain (57.1%), anal incontinence (94.1%), difficult evacuation (29.4%), urgency (64.7%) and intolerance of rectal therapies (35.3%); rectal inflammation was not correlated with the presence of symptoms in our study group (p= 0.53). Modified manometric parameters were found in 81.0% patients and were associated with previous pelvic surgical interventions (p<0.05); although, the latter does not seem to increase the risk of incontinence (p= 0.33). In 61.9% cases the manometric measurements correlated with the symptoms. 85% of the patients with passive incontinence presented lower resting pressure and 57.1% of those with active incontinence were found with lower squeeze pressures. Changes compatible with dyssynergia were detected in 61.9% of the cases. Sensory testing revealed alterations in 46.2% of patients, and RAIR was negative in 33.3% of the cases. Conclusions. There was a considerable number of patients with anorectal motility changes. Therefore, pelvic floor investigation is an essential tool in the management of IBD patients with anorectal syptoms. [ABSTRACT FROM AUTHOR]

Introduction. Celiac disease (CD) malabsorption may provoke various extraintestinal features like neurological disorders with a powerful impact on the patient's life. Gluten enteropathy diagnosis may be delayed and therewith the cancer risk may increase. Case presentation. A 35-year old epileptic male patient was admitted with newly onset abdominal pain, vomiting, jaundice and weight loss. The abdominal ultrasonography (US) showed ductal criteria for chronic pancreatitis (CP): irregular duct contour, visible side branches, hyperechoic duct margins and dilated main duct. Besides hepatic cholestasis and cytolysis, the blood tests showed significant lipase elevation, suggesting acute pancreatitis (AP). The upper digestive endoscopy using the side-viewing endoscope revealed the loss of duodenal folds with scalloping appearance. Advancing towards the second part of the duodenum this aspect became more irregular with an infiltrative and stenosing appearance. The biopsies showed poorly differentiated duodenal adenocarcinoma with diffuse areas of signet ring cells, respectively marked villous atrophy: Corazza-Villanacci grade B2. The tTGA were positive at high titer, same as HLA DQ2. Cephalic pancreaticoduodenectomy was performed, with clear resection margins - G3, pT3N0M0. Following surgery, besides the jaundice remission, the patient's neurological status considerably improved under optimized treatment and gluten free diet (GFD). At 6 months follow-up there were no signs of tumor residue, the patient gained weight, US revealed no signs of pancreatitis and the seizures bouts were less frequent. Discussions. There is a 60-to 80-fold increased risk of small bowel carcinoma in patients with celiac disease (CD), a long-standing or refractory disease increasing even more the risk of malignancy. In this case the morbidity was higher due to development of acute pancreatitis episodes on CP, caused by the ampular obstruction. Patients with CD have an increased risk of CP and AP, but the strength of these associations as well as the implied mechanisms are not very well clarified. A Swedish retrospective study found that patients with CD had a 3-fold increased risk of developing pancreatitis, with a lower hazard ratio for gallstone related AP comparative with nongallstone related AP. We consider that the association with the neurological disorder might be only incidental since the imaging found no occipital calcifications specific to a seizure syndrome associated with CD. Conclusions. Gluten enteropathy is a complex disease associating multiple extraintestinal symptoms. An early diagnosis with early GFD reduce the risk of small bowel carcinoma and definitely can prevent other extraintestinal manifestations. [ABSTRACT FROM AUTHOR]

Introduction. Patients with end-stage liver diseases, included on the waiting list (WL) for liver transplant (LT) can develop complications that increase the morbidity and mortality, due to different risk factors. The aim was to evaluate different prognostic factors for mortality in patients included on the WL for LT. Materials and Methods. We performed a singlecenter retrospective cohort study from 1 January, 2018 to 31 December, 2022, in 120 patients included on the WL for LT. We analyzed the following prognostic factors: MELD, MELD Na, MELD 3.0, ALBI, occurrence of acute-on-chronic liver failure (ACLF) from grade 1 to 3, occurrence of liver cirrhosis complications, infections, neutrophil-to-lymphocyte ratio (NLR), lymphocyte-to-monocyte ratio, plateletto-lymphocyte ratio, using univariable and multivariable Cox proportional hazards models. Results. From 120 patients included, 63.3% were males, with a median age of 55 ± 11.55 years. The most frequent etiology of the liver disease was B + delta hepatitis viral infection in 35.8%, followed by alcoholic etiology in 35% of cases. 30.8% of patients had hepatocellular carcinoma. The median MELD Na score at the inclusion on the waiting list was 17 ±7.3. During the follow-up on the waiting list, 39.2% of patients had infectious complications, such as spontaneous bacterial peritonitis (SBP), pneumonia, urinary tract infections and cellulitis. The median waiting time for all patients was 300 ± 686 days. Liver transplant was performed in 66.7% of cases, and 22.5% patients died during follow-up. Univariate analysis demonstrated that the following factors were associated with higher death rates: presence of ACLF (p<0.0001), refractory ascites (p=0.012), acute kidney injury (p=0.0007), hepatic encephalopathy (p=0.0064), infectious complications (p=0.0077), higher MELD score (p=0.043), MELD Na score (p=0.0048) and MELD 3.0 (p=0.0053), higher NLR (p=0.0011). Multivariate analysis was performed and the presence of ACLF (p=0.0051) and a higher NLR (p=0.042) were found to be independent predictors for mortality. Conclusions. In patients included on the waiting list for liver transplant, occurrence of acute-on-chronic liver failure and neutrophil-to-lymphocyte ratio can be used as predictive factors for mortality. [ABSTRACT FROM AUTHOR]

Introduction. Even if for a long time patients with IBD were considered malnourished and underweight, there is an important subgroup suffering from obesity and overweight. Aim. The aim of this study was to assess how obesity influences the response to treatment and the evolution of IBD. Materials and Methods. We perform a retrospective observational study including102 patients divided into 23 patients with obesity (BMI>30kg/m2)-22.5%, 41 overweight patients (BMI> 25kg/m2)-40.1%, 33 normal weight patients (BMI 18.5-25 kg/m2)- 32% and 5 underweight pacients (BMI <18.5)- 4.9% out of 177 patients with IBD admitted in our center during 1st Jan 2022-31 Dec 2022. Because of lack of data 75 patients were excluded from this study. We decided to organise the patients in 2 groups: G1- obese and overweight and G2- normal weight patients. Results: There were 64.7% CD patients (24.2% obese, 39.4% overweight) and 35.3% UC patients(a lower percentage of obese patients 19.4% but similar for overweight patients 41.7%). Also, obesity and overweight was more frequently identified at male patients than female patients(70.8%vs 48.6%) and it seems to be more common for people over 40 years old(67.1% of our patients). CD patients from G1 had a lower prevalence of penetrating disease 4.7% vs 21.2% from G2 patients, but higher rates of perianal disease(26.2% vs 12.1%). Obesity seems not affect the extension of UC disease as G1 and G2 patients present the most common form- pancolitis 45.5% and 61.5%. Anti-TNF medication was preferred for both categories(48.4% Infliximab and 26.5% Adalimumab for G1vs 42.4% and 24.2% for G2), with the mention that 46.9% of G1 patients vs 21.2% of G2 patients required the optimization of the dose of biological treatment, but with similar rates of switch with another biosimilar. The prior surgery was comparable for both groups(28.1% G1 vs 21.2% G2), with a preference for laparoscopic surgery 54.1% vs 35% for the last category(G2) and also a lower risk of postoperative complications (3% vs 20%). Conclusion: Patients with IBD present rates similar to the general population of obesity prevalence. Also, obesity seems to be involved in maintaining a chronic proinflammatory status of these patients, with a poor response to therapies that are not weight-based and intravenously administered, frequently requiring to escalate the treatment dose and a more difficult laparoscopic access for surgery with a higher risk of developing postoperative complications. [ABSTRACT FROM AUTHOR]

Introduction. Hereditary colorectal cancer (HCRC) syndromes represent a relatively diverse group of disorders that exhibit different patterns of inheritance. We aim to create the first registry of this type for this category of patients in order for them to have access to better healthcare and to give them a new perspective Keyword: colorectal cancer, hereditary syndromes, cancer registry Materials and Methods. We started collecting data since August 2021. We made an extensive examination consisting of personal infromation and important clinical data. All patients introduced in the study had lower and upper GI examinations performed, and also CT exams when indicated by guidelines. For Lynch Syndrome we used the Amsterdam and Bethesda criteria, while for familial adenomatous polyposis syndrome we combined the colonoscopy results with family history. We also collected family information in order to be able to perform screening testing for them depending on their respective syndrome. Results. We managed to introduce 26 patients that have either a genetic, histological or clinical diagnosis. Out of these, some are only family members that haven't been genetically tested and aren't diagnosed yet, but still have to be followed. We have 22 index patients, and are currently actively following other family members at high risk. We have 6 Lynch Syndrome families, 2 Peutz-Jeghers families, 3 Attenuated FAP Syndrome families, 2 MAP families, 7 FAP families and one Juvenile polyposis syndrome family with a sex distribution male to female of 9:17, (34.61% male, 65.39% female). Both patients with MAP have had genetic testing done, and also the Juvenile polyposis patient. Currently, family members are being introduced into the study in order to perform screening examinations according to guidelines and create an efficient timetable that can help prevent complications and diagnosis of advanced tumours. Conclusion. While challenging, it is clear that there is an urgent need for an electronic registry in order to offer this category of pacients a better life expectancy and a better quality of life. [ABSTRACT FROM AUTHOR]

Background & aims. In our country prospective studies to establish the prevalence of obesity and non-alcoholic fatty liver disease (NAFLD) are lacking. We prospectively assessed the prevalence and severity of NAFLD in a cohort of asymptomatic patients attending the national screening programme for colorectal cancer. Methods. Screening for NAFLD was performed using abdominal ultrasound and Fibroscan with CAP module. Also antropometric parameters, comorbidities like diabetes and arterial hypertension, and risk behaviours like smoking and alcohol consumption were evaluated Results. We screened 70 patients with FIT positive tests, attending for colonoscopy. The mean age was 60 ± 7.0 years, 48.5% were male, the mean BMI was 28.46 ± 4.54 kg/m2, and 37,1% were obese. The prevalence of NAFLD as evaluated as any degree of steatosis on Fibroscan with CAP module was 79.7% and the prevalence of severe steatosis was 26.6%. Significant fibrosis (F =2) was present in 13.8%. In a multivariable logistic analysis, the only factor associated with the presence of NAFLD was waist cirumference at high risk (>102 cm in men and >88 cm in women) Conclusion. The obesity and NAFLD incidence rate in asymptomatic general population is high and worrying. Abdominal obesity seems to be more predictable than BMI for the diagnosis of fatty liver. [ABSTRACT FROM AUTHOR]

The article describes the case of a 56-year old woman who was diagnosed with alpha fetoprotein (AFP)-producing colon cancer. The patient underwent blood tests, upper endoscopy, colonoscopy, computed tomography scan of the thorax, abdomen and pelvis, liver and colon biopsy. Blood test results revealed increased liver enzymes, mild cholestasis and inflammatory syndrome, while immunohistochemistry results included tubulo-papillary pattern, liver metastasis and synaptophysin positive cells.

[Display omitted] • The methods for pancreatic cancer monitoring have a latency in indicating disease progression. • Cell-free DNA is the most extensively studied type of liquid biopsy in pancreatic adenocarcinoma. • Circulant tumor DNA indicates increased aggressiveness of resectable or unresectable tumors and if detected during treatment. • Associations of KRAS mutations and prognosis in unresectable cases is to be determined. This systematic review and meta-analysis evaluated the prognostic role of cell-free DNA (cfDNA) in pancreatic ductal adenocarcinoma (PDAC). Eligible studies reported differences in overall (OS) and progression-free survival (PFS) by cfDNA status. The random effect model yielded the pooled hazard ratios (HRs) and 95 % confidence intervals (CI). Detection of circulant-tumor DNA (ctDNA), KRAS mutations and other cfDNA alterations constitute detectable cfDNA biomarkers. Altogether, 38 studies (3,318 patients) were eligible. Progression-free and overall survival were decreased with detectable ctDNA (HR = 1.92, 95 %CI:(1.29,2.86); HR = 2.25, 95 %CI:(1.73,2.92)) and KRAS mutations (HR = 1.88, CI:1.22,2.92,); HR = 1.52, 95 %CI:(1.22,1.90)) respectively, across various stages. In unresectable cases, ctDNA (HR = 2.50, 95 %CI:(1.94,3.23)), but not KRAS mutations (HR = 1.16, 95 %CI:(0.46,2.94)) signaled risk for progression. Detectable cfDNA biomarkers correlated with worse prognosis in resectable cases and if detected during treatment. In conclusion, cfDNA biomarkers indicate accelerated progression and decreased survival in PDAC. Significance of KRAS mutations detection in unresectable cases is to be determined. [ABSTRACT FROM AUTHOR]