Updates in Diagnosis and Endoscopic Management of Cholangiocarcinoma.

Cholangiocarcinoma (CCA) is an adenocarcinoma originating from the epithelial cells of the bile ducts/hepatocytes or peribiliary glands. There are three types of cholangiocarcinoma: intrahepatic, perihilar and distal. CCA represents approximately 3% of the gastrointestinal malignancies. The incidence of CCA is higher in regions of the Eastern world compared to the Western countries. There are multiple risk factors associated with cholangiocarcinoma such as liver fluke, primary sclerosing cholangitis, chronic hepatitis B, liver cirrhosis and non-alcoholic fatty liver disease. Endoscopy plays an important role in the diagnosis and management of cholangiocarcinoma. The main endoscopic methods used for diagnosis, biliary drainage and delivering intrabiliary local therapies are endoscopic retrograde cholangiopancreatography and endoscopic ultrasound. The purpose of this review is to analyze the current data found in literature about cholangiocarcinoma, with a focus on the actual diagnostic tools and endoscopic management options.

Exceptional Liver Transplant Indications: Unveiling the Uncommon Landscape.

Liver transplantation represents the definitive intervention for various etiologies of liver failure and encompasses a spectrum of rare indications crucial to understanding the diverse landscape of end-stage liver disease, with significantly improved survival rates over the past three decades. Apart from commonly encountered liver transplant indications such as decompensated cirrhosis and liver cancer, several rare diseases can lead to transplantation. Recognition of these rare indications is essential, providing a lifeline to individuals facing complex liver disorders where conventional treatments fail. Collaborative efforts among healthcare experts lead not only to timely interventions but also to the continuous refinement of transplant protocols. This continued evolution in transplant medicine promises hope for those facing diverse and rare liver diseases, marking a paradigm shift in the landscape of liver disease management.

Considering Histologic Remission in Ulcerative Colitis as a Long-Term Target.

Monitoring disease activity in inflammatory bowel disease (IBD) is challenging since clinical manifestations do not represent reliable surrogates for an accurate reflection of the inflammatory burden. Endoscopic remission had been the most significant endpoint target in the last years; nevertheless, a remarkable proportion of patients continue to relapse despite a normal-appearing mucosa, highlighting that endoscopy may underestimate the true extent of the disease. A subtle hint of the importance that histology plays in the long-term course of the disease has been endorsed by the STRIDE-II consensus, which recommends considering histologic healing for ulcerative colitis (UC), even though it is not stated to be a compulsory formal target. It is a continuum-changing paradigm, and it is almost a certainty that in the near future, histologic healing may become the new formal target for ulcerative colitis. It must be emphasized that there is great heterogeneity in defining histological remission, and the main criteria or cut-off values for inflammatory markers are still in an ill-defined area. The complexity of some histologic scores is a source of confusion among clinicians and pathologists, leading to low adherence in clinical practice when it comes to a homogenous histopathological report. Therefore, a standardized and more practical approach is urgently needed.

Recombinant Tissue Plasminogen Activator: The New Concept for Dissolving Septae in Loculated Peri-pancreatic Fluid Collection prior to Endoscopic Drainage. A Case Report.

Peri-pancreatic fluid collections are late complications of acute pancreatitis. Loculated peri-pancreatic fluid collections, even rare, remain the "black sheep" in terms of drainage, due to difficulty to puncture all compartments, thus prohibiting proper drainage of all compartments. Recombined tissue plasminogen activator (r-tPA) has been advocated as treatment of the loculated collections, due to its ability to dissolve the fibrinous strands and thus facilitate proper drainage. We report the case of a 58 years-old male presenting with a painful loculated peri-pancreatic fluid collection secondary to acute pancreatitis. We performed Alteplase injection, followed by successful endosonographic drainage with lumen apposing metal stent of the collection after 48 hours. Our observation suggests that r-tPA could be a new strategy for loculated collections management, ensuring better drainage and limiting the indication for surgical treatment.

Duodenal Gangliocytic Paragangliomas-Case Series and Literature Review.

Duodenal gangliocytic paragangliomas are rare neuroendocrine tumors primarily localized in the periampullary area. Though mostly asymptomatic, they can present with various symptoms, most often jaundice, anemia and abdominal pain. The present paper is a case series report, describing our personal experience with patients presenting to the Emergency Unit with different symptoms due to duodenal gangliocytic paraganglioma. Endoscopic resection is safe and indicated in most of the cases, being also associated with lower medical costs. EUS plays a central role in the pre-resection management and in surveillance, and immunostaining is decisive to ascertain the tumor histologic origin. In addition to reporting our experience, we researched the literature regarding these rare tumors and performed a comprehensive review.

Artificial Intelligence-The Rising Star in the Field of Gastroenterology and Hepatology.

Artificial intelligence (AI) is a term that covers a multitude of techniques that are used in a manner that tries to reproduce human intelligence. AI is helpful in various medical specialties that use imaging for diagnostic purposes, and gastroenterology is no exception. In this field, AI has several applications, such as detecting and classifying polyps, detecting the malignancy in polyps, diagnosing Helicobacter pylori infection, gastritis, inflammatory bowel disease, gastric cancer, esophageal neoplasia, and pancreatic and hepatic lesions. The aim of this mini-review is to analyze the currently available studies regarding AI in the field of gastroenterology and hepatology and to discuss its main applications as well as its main limitations.

Surgery for Inflammatory Bowel Disease in the Era of Biologic Therapy: A Multicenter Experience from Romania.

Background and Objectives: Biologic therapy has fundamentally changed the opportunity of medical treatment to induce and maintain remission in inflammatory bowel disease (IBD). Nevertheless, the rate of surgery is still at a very high rate, profoundly affecting the quality of life. We aimed to analyze surgical cases at three major IBD units in order to identify the main risk factors and the impact of biologic therapy on pre- and postsurgical outcomes. Material and Methods: This was a multicenter retrospective cohort study that included 56 patients with IBD-related surgical interventions from 3 tertiary care hospitals in Bucharest, Romania. The study was conducted between January 2017 and June 2021. All data were retrospectively collected from the medical records of the patients and included the age at diagnosis, age at the time of surgery, IBD type and phenotype, biologic therapy before or/and after surgery, timing of biologic therapy initiation, extraintestinal manifestations, type of surgery (elective/emergency), early and long-term postoperative complications and a history of smoking. Results: A low rate of surgical interventions was noted in our cohort (10.3%), but half of these occurred in the first year after the IBD diagnosis. A total of 48% of the surgical interventions had been performed in an emergency setting, which seemed to be associated with a high rate of long-term postoperative complications. We found no statistically significant differences between IBD patients undergoing treatments with biologics before surgery and patients who did not receive biologics before the surgical intervention in terms of the IBD phenotype, type of surgery and postoperative complications. Conclusion: Our study showed that biologics initiated before the surgical intervention did not influence the postoperative complications. Moreover, we demonstrated that patients with Crohn's disease and no biologics were the most susceptible to having to undergo surgery. Conclusion: In conclusion, the management of patients with IBD requires a multidisciplinary approach that considers an unpredictable evolution.

Efficacy of Endobiliary Radiofrequency Ablation in Preserving Survival, Performance Status and Chemotherapy Eligibility of Patients with Unresectable Distal Cholangiocarcinoma: A Case-Control Study.

BACKGROUND: Cholangiocarcinoma is the most common malignancy of the bile ducts causing intrahepatic, hilar, or distal bile duct obstruction. Most jaundiced patients are diagnosed with unresectable tumors in need for palliative bile duct drainage and chemotherapy. Endobiliary radiofrequency ablation (RFA) is an adjuvant technique that may be applied prior to biliary stenting. The aim of our study was to assess the efficacy of endobiliary RFA prior to stent insertion in patients with unresectable distal cholangiocarcinomas. METHODS: Twenty-five patients (eight treated with RFA and stenting and 17 treated with stenting alone) were included in a case-controlled study. We prospectively assessed the impact of RFA on the survival rate, the patient performance status, and the preservation of eligibility for chemotherapy based on the patient laboratory profile. RESULTS: Patients treated with RFA prior to stenting proved to have a significantly longer survival interval (19 vs. 16 months, p = 0.04, 95% CI) and significantly better performance status. Moreover, the laboratory profiles of patients treated with RFA has been proven superior in terms of total bilirubin, liver enzymes, and kidney function, thus making patients likely eligible for palliative chemotherapy. Post-ERCP adverse events were scarce in both the study group and the control group. CONCLUSION: Given the isolated adverse events and the impact on the patient survival, performance, and laboratory profile, RFA can be considered safe and efficient in the management of patients with unresectable distal cholangiocarcinomas.

Endoscopic Management of Biliary Strictures after Orthotopic Liver Transplantation: A Single Center Experience Study.

Background and Aim. Endoscopic therapy is the method of choice in the management of biliary strictures after orthotopic liver transplantation (OLT). Even though the mainstay approach for OLT stricture complications is represented by consecutive procedures of multiple plastic stents (MPS) insertion, a valuable alternative is the use of fully covered self-expandable metal stents (FCSEMS). The aim of the study was to compare MPS with FCSEMS used in the management of OLT biliary strictures, in terms of clinical outcomes and complications. Material and Methods. This is a retrospective, single-center study conducted between February 2014 and November 2019 in the Clinical Emergency Hospital of Bucharest, Romania. We enrolled all consecutive patients who developed biliary strictures after OLT and were treated by endoscopic retrograde cholangiopancreatography (ERCP) either with MPS or FCSEMS. Results. Thirty-six patients were included in the study, 27 patients had MPS and nine patients had FCSEMS. 106 ERCP procedures were performed and 159 stents were inserted. The mean number of ERCP procedures required per patient was significantly higher for MPS than for FCSEMS (3.34 ± 1.46 vs. 2.11 ± 0.33, p < 0.001). In the FCSEMS group only one patient had three procedures, due to stent migration. Difficult cannulation was encountered in 22 patients, 18 patients from MPS group and four patients from FCSEMS group. Dilation was performed in 20 (77%) MPS patients and in four FCSEMS patients (44%). Overall, we used 159 stents for stricture resolution, 149 plastic stents and 10 FCSEMS. Mean number of stents inserted was significantly lower in the FCSEMS group compared to MPS group (1.16 ± 0.40 vs. 5.73 ± 2.64, p < 0.001). Conclusions. Stricture resolution using FCSEMS is comparable to MPS and even has some advantages. In line with prior studies, FCSEMS are effective, with fewer complications and similar outcome compared to plastic stents. Other particular aspects should be further assessed, especially long-term follow up of FCSEMS and their cost efficiency.

The Prevalence and Predictors of Restless Legs Syndrome in Patients with Liver Cirrhosis.

INTRODUCTION AND AIM: Sleep disorders are highly prevalent in patients with liver cirrhosis. The aim of this study was to investigate the prevalence of restless legs syndrome (RLS), as well as its risk factors and possible predictors, in a cohort of patients with liver cirrhosis. MATERIAL AND METHODS: We performed a cross-sectional prospective study over a period of 14 months and enrolled 69 patients with liver cirrhosis, after applying the inclusion and exclusion criteria. The cases of RLS were assessed according to the International Restless Legs Syndrome Study Group (IRLSSG) criteria and severity scale. RESULTS: Out of the total number of patients, 55% fulfilled the criteria for RLS. Age, diabetes, severity of cirrhosis, serum creatinine, glomerular filtration rate (GFR), and mean hemoglobin were associated with the presence of RLS. Moreover, there was a significantly higher prevalence of RLS among patients with decompensated cirrhosis. From all the risk factors introduced into the multivariate analysis, only the GFR could predict the presence of RLS. CONCLUSIONS: This research shows that patients with liver cirrhosis have a high risk of RLS. Even though there are multiple risk factors associated with RLS, only the GFR could predict its occurrence in our cohort.

The Prevalence and Association of Cognitive Impairment with Sleep Disturbances in Patients with Chronic Liver Disease.

Introduction/Aim. The aim of this study was to assess the prevalence of cognitive impairments and their association with sleep patterns in a cohort of patients diagnosed with chronic liver disease (CLD). Material and methods. The present paper is a prospective cohort study, carried out over a period of 12 months, among patients with various stages of CLD. We evaluated the cognitive function through psychometric hepatic encephalopathy score (PHES), while sleep was assessed by actigraphy and two self-reported questionnaires: Epworth Sleepiness Scale (ESS) and Pittsburgh Sleep Quality Index (PSQI). Results. Seventy-four patients with CLD were considered eligible and were enrolled between December 2020−November 2021. The prevalence of minimal hepatic encephalopathy (MHE) in the entire cohort was 41.9%, and the diagnosis was considered for PHES scores ≤ −3. Patients with cirrhosis recorded significantly lower PHES scores compared to patients with other CLDs but without cirrhosis (−3.19 ± 3.89 vs. 0.19 ± 2.92, p < 0.05). Patients who exhibited MHE suffered from poor sleep, daytime somnolence, disturbed nighttime sleep, and low overall sleep efficacy. Patients diagnosed with MHE and undergoing treatment with lactulose and/or rifaximin for prevention of overt hepatic encephalopathy (HE) showed better results in terms of sleep parameters compared to patients diagnosed with MHE but without treatment. Conclusions. This research increases awareness regarding the connection between sleep features and MHE in patients with cirrhosis and other CLDs. A deeper insight into the subclinical stages of HE and associated sleep disturbances is warranted in future studies.

Impact of biliary stenting in endoscopic ultrasound-guided tissue acquisition among patients with pancreatic cancer.

INTRODUCTION: Pancreatic malignancies represent highly fatal diseases with poor prognosis and constantly increasing incidence despite modern diagnostic and therapeutic options. Both endoscopic ultrasound (EUS) and endoscopic retrograde cholangiopancreatography (ERCP) are regarded as mainstays in pancreatic cancer management. The present study aims to evaluate whether accuracy EUS with fine-needle aspiration or biopsy (FNA or FNB) in pancreatic cancer diagnosis is influenced by prior biliary stenting or by technical or anatomical features (stent type, number of needle passes, common bile duct or Wirsung's diameter, topographical characteristics and diameter of the pancreatic tumor). MATERIALS AND METHODS: This retrospective study includes 243 patients with pancreatic cancer who underwent ERCP and EUS with fine-needle aspiration or biopsy (FNA or FNB). RESULTS AND DISCUSSION: Out of the total number of patients, 68 were stented prior to EUS. We found that the EUS-FNA diagnostic yield is not influenced either by the presence of biliary stent, nor by the type of stent (plastic or metallic). Moreover, the mean needle passes required were similar for both stented patients and not stented ones. CONCLUSIONS: Ultimately, given our results, we can state that EUS-FNA/FNB can be safely and accurately performed in the presence of biliary stents.

Risk Factors for Pancreatic Cancer: Emerging Role of Viral Hepatitis.

Pancreatic cancer is one of the most aggressive malignant neoplastic diseases. The incidence and mortality rates of this disease vary depending on geographical area, which might be explained by the different exposure to risk factors. To improve the prognosis of patients with pancreatic cancer, different approaches are needed for an earlier diagnosis. Identification of risk factors and implementation of screening strategies are essential for a better prognosis. Currently, the risk factors for pancreatic cancer fall into two broad categories, namely extrinsic and intrinsic factors. Extrinsic factors include alcohol consumption, smoking, a diet rich in saturated fats, and viral infections such as chronic infection with hepatitis B and C viruses. The pathophysiological mechanisms explaining how these hepatotropic viruses contribute to the development of pancreatic cancer are not fully elucidated. The common origin of hepatocytes and pancreatic cells in the multipotent endodermal cells, the common origin of the blood vessels and biliary ducts of the pancreas and the liver, or chronic inflammatory changes may be involved in this interaction. A careful monitoring of patients with viral liver infections may contribute to the early diagnosis of pancreatic cancer and improve the prognosis of these patients.

Assessment of Sleep among Patients with Chronic Liver Disease: Association with Quality of Life.

The present study aims to assess the sleep characteristics and health-related quality of life (HRQOL) among patients with chronic liver diseases (CLDs), as well as the relationship between them. We conducted a prospective cross-sectional study, over a period of eight months, on patients with CLDs. Sleep was assessed by subjective tools (self-reported validated questionnaires), semi-objective methods (actigraphy), and HRQOL by using the 36-Item Short Form Survey (SF-36) and Chronic Liver Disease Questionnaire (CLDQ). The results indicated that 48.21% of patients with CLDs had a mean Pittsburgh Sleep Quality Index (PSQI) score higher than five, suggestive of poor sleep; 39.29% of patients had a mean Epworth Sleepiness Scale (ESS) score ≥11, indicative of daytime sleepiness. Actigraphy monitoring showed that patients with cirrhosis had significantly more delayed bedtime hours and get-up hours, more awakenings, and more reduced sleep efficacy when compared to pre-cirrhotics. The CLDQ and SF-36 questionnaire scores were significantly lower in cirrhotics compared to pre-cirrhotics within each domain. Moreover, we identified significant correlations between the variables from each questionnaire, referring to HRQOL and sleep parameters. In conclusion, sleep disturbances are commonly encountered among patients with CLDs and are associated with impaired HRQOL. This is the first study in Romania that assesses sleep by actigraphy in a cohort of patients with different stages of CLD.

Gastrointestinal Stromal Tumors-A Mini Review.

Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal neoplasms of the gastrointestinal tract. They are potentially malignant, and have an unpredictable evolution. The origin of these tumors is in the interstitial cells of Cajal, which are cells that are interposed between the intramural neurons and the smooth muscle cells of the digestive tract. GISTs are characterized by mutations in the gene c-Kit, but also other mutations, such as those of the platelet-derived growth factor receptor alpha. The most common locations of these tumors are the stomach and small intestine, although they can occur at any level of the digestive tract and occasionally in the omentum, mesentery and peritoneum. Most cases of GISTs are sporadic, and about 5% of cases are part of family genetic syndromes. The correct diagnosis of GIST is determined by histopathological examination and immunohistochemistry. According to histopathology, there are three main types of GISTs: spindle cell type, epithelioid type and mixed type. The therapeutic management of GIST includes surgery, endoscopic treatment and chemotherapy. The prognosis of patients with GIST varies depending on a number of factors, such as risk category, GIST stage, treatment applied and recurrence after treatment.

Comprehensive Overview of Sleep Disorders in Patients with Chronic Liver Disease.

The impact of sleep disorders (SDs) on patients with chronic liver diseases (CLD) is tremendous. SDs are frequently encountered among these patients and interfere with their quality of life. This review aims to present the data available so far about the prevalence, phenotypes, and proposed pathophysiological mechanisms of SDs in CLD. Moreover, we proposed to search the literature regarding the most reliable methods to assess SDs and the possible therapeutic options in patients with CLD. The main results of this review show that when it comes to prevalence, the percentages reported vary widely between studies performed among populations from the USA or Europe and those coming from Asian countries. Furthermore, it has been proven that SDs may also be present in the absence of neurocognitive disorders attributable to hepatic encephalopathy (HE), which contradicts traditional suppositions where SDs were considered part of the clinical scenario of HE. Currently, there are no specific recommendations or protocols to assess SDs in CLD patients and data about the therapeutic management are limited. Taking into consideration their impact, a protocol for diagnosing and managing SDs should be developed and included in the daily practice of hepatologists.

Is There a Relationship between COVID-19 and Hyponatremia?

Nowadays, humanity faces one of the most serious health crises, the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic. The severity of coronavirus disease 2019 (COVID-19) pandemic is related to the high rate of interhuman transmission of the virus, variability of clinical presentation, and the absence of specific therapeutic methods. COVID-19 can manifest with non-specific symptoms and signs, especially among the elderly. In some cases, the clinical manifestations of hyponatremia may be the first to appear. The pathophysiological mechanisms of hyponatremia among patients with COVID-19 are diverse, including syndrome of inappropriate antidiuretic hormone secretion (SIADH), digestive loss of sodium ions, reduced sodium ion intake or use of diuretic therapy. Hyponatremia may also be considered a negative prognostic factor in patients diagnosed with COVID-19. We need further studies to evaluate the etiology and therapeutic management of hyponatremia in patients with COVID-19.

The non-invasive assessment of hepatic fibrosis.

Hepatic disease accounts for approximately 2 million deaths/year worldwide. Liver fibrosis, as the last stage of numerous chronic liver diseases, is one of the most relevant prognostic factors. The liver biopsy with the histopathological examination is considered to be the "gold standard" for the identification and staging of the hepatic fibrosis. However, liver biopsy is known as an invasive investigation that has multiple limitations. Research studies conducted in the last few years focused on identifying non-invasive type methods for the evaluation of hepatic fibrosis; usually, there are 2 categories of such investigations: serologic tests and imaging techniques. This narrative review presents the non-invasive investigation methods used in the liver fibrosis evaluation. New molecular perspectives on fibrogenesis and fibrosis regression, as well as the appearance of therapeutic antifibrotic agents, justify the necessity of non-invasive tools to detect and grade liver fibrosis.

What is the Impact of the Proportion of Solid Necrotic Content on the Number of Necrosectomies during EUS-Guided Drainage using Lumen-Apposing Metallic Stents of Pancreatic Walled-off Necrosis ?

BACKGROUND AND AIMS: The fully-covered, lumen apposing metal stents are designed for one step placement, facilitating the direct endoscopic necrosectomy into the walled-off pancreatic necrosis. However, the prediction of the number of necrosectomy sessions in these patients is not known. This study evaluated the association between the proportion of solid necrotic material inside walled-off necrosis, as assessed during the endosonography placement of a lumen apposing metal stent, and the number of necrosectomies subsequently required. METHODS: Patients from three tertiary medical centers with symptomatic walled off pancreatic necrosis (pain, infection, gastric/biliary obstruction) at more than 4 weeks after onset of acute pancreatitis were retrospectively analysed. Proportion of solid necrotic debris was estimated during endosonography procedure of lumen apposing metal stents placement. Necrosectomy was performed when obstruction or inflammation occurred subsequently. Lumen apposing metal stents were removed after clearance of necrotic content. RESULTS: In 46 patients with successful lumen apposing metal stents placement, necrosectomy was performed in 39 patients (72.78%). Performance of 3 or more necrosectomies was significantly associated with more than 50% pancreatic necrosis (p=0.032), but not with walled-off pancreatic necrosis size or location. Necrotic infection during lumen apposing metal stents stenting was associated with hypoalbuminemia, but not with necrosectomy requirement. Clinical success after a median follow-up of 13.37 months was 87%. CONCLUSIONS: Walled-off pancreatic necrosis with more than 50% solid necrotic content were associated with more necrosectomy procedures, requiering longer endoscopy time, intravenous sedations, and higher costs.

Early Diagnosis of Pancreatic Cancer: The Key for Survival.

Pancreatic cancer (PC) is one of the most aggressive forms of cancer. Negative prognosis is mainly due to the late diagnosis in advanced stages, when the disease is already therapeutically overcome. Studies in recent years have focused on identifying biomarkers that could play a role in early diagnosis, leading to the improvement of morbidity and mortality. Currently, the only biomarker widely used in the diagnosis of PC is carbohydrate antigen 19-9 (CA19.9), which has, however, more of a prognostic role in the follow-up of postoperative recurrence than a diagnostic role. Other biomarkers, recently identified as the methylation status of ADAMTS1 (A disintegrin and metalloproteinase with thrombospondin motifs 1) and BNC1 (zinc finger protein basonuclin-1) in cell-free deoxyribonucleic acid (DNA), may play a role in the early detection of PC. This review focuses on the diagnosis of PC in its early stages.