Showing papers in "Expert Review of Gastroenterology & Hepatology in 2021"

Recent advances of immunotherapy for biliary tract cancer.

Abstract: Introduction: Biliary tract cancer (BTC) is a heterogeneous group of aggressive malignancies comprising intrahepatic cholangiocarcinoma, extrahepatic cholangiocarcinoma, gallbladder cancer, and ampulla of Vater cancer. Although recent years have witnessed the emergence of novel treatment targets, medical therapy remains a compelling challenge in these hepatobiliary malignancies. In order to provide more effective treatment options, immune checkpoint inhibitors (ICIs) are currently under investigation in advanced BTC, with controversial results reported so far.Areas covered: This review provides an overview regarding current scenario of ICIs and immune-based combinations in advanced BTC, where several novel treatments are currently being developed, some of which have suggested interesting efficacy in recent clinical trials. In addition, we provide a report of ongoing Phase I to III clinical trials assessing ICIs and new immunotherapeutic strategies for advanced BTC.Expert opinion: Although immunotherapy has revolutionized the treatment landscape of several hematological and solid tumors, the role of ICIs and immune-based combinations in advanced BTC is still unclear. Despite ICI monotherapy has reported limited efficacy in this setting, the durable responses observed in sporadic cases suggest that testing patients for MMR, MSI, TMB, and PD-L1 expression is warranted. Results of currently ongoing trials are highly awaited.

First-line immune checkpoint inhibitor-based combinations in unresectable hepatocellular carcinoma: current management and future challenges.

Abstract: Introduction Immunotherapy has recently taken on an extremely important role in medical oncology, as first- or later-line treatment in several tumor types, and recent years have seen the emerging of clinical trials assessing immune checkpoint inhibitors (ICIs) in unresectable hepatocellular carcinoma (HCC). Areas covered Herein, we provide an overview of recently published studies exploring the dual immune checkpoint blockade or the combination of ICIs plus biological treatments as first-line treatment in HCC patients with advanced disease, especially focusing on the biological rationale behind these therapeutic strategies, and ongoing active and recruiting clinical trials. Expert opinion Results of studies on monotherapy with ICIs have suggested that this strategy could be beneficial only in a minority of patients; conversely, the recently published IMbrave150 study has reported an overall survival benefit in HCC receiving the combination of atezolizumab plus bevacizumab compared to sorafenib as first-line treatment. A wide number of clinical trials is evaluating ICI-based combinations in advanced HCC, a strategy which is supported by robust preclinical and early-phase clinical data, and results of these studies are highly awaited.

Current epidemiology in hepatocellular carcinoma.

Abstract: IntroductionHepatocellular carcinoma (HCC) is the sixth most common cancer and the third-leading cause of cancer-related mortality in the world.Areas coveredThis review will discuss risk factors, demographic differences, global trends, and the economic burden of HCC. Viral hepatitis, particularly hepatitis B virus (HBV) infection, is the most common underlying liver disease leading to HCC in those with cirrhosis. Other important risk factors include alcoholic liver disease, nonalcoholic fatty liver disease, metabolic syndrome, etc. With the introduction of direct-acting antiviral agents for hepatitis C virus infection, routine vaccination against HBV, and increasing support for robust public screening programs, the incidence rates for HCC due to viral hepatitis is falling in many countries. Meanwhile, the prevalence of obesity and metabolic syndrome are on the rise, as is NAFLD-related HCC incidence. Asia and Africa have the highest incidence rates of HCC. In multiethnic countries, racial and ethnic minorities experience disparities in HCC incidence as well as mortality, representing an essential area for improvement in terms of healthcare inequity.Expert opinionInterventions to minimize the global burden of HCC aim to reduce rates of the most common risk factors and implement effective treatment of underlying etiology and comprehensive screening programs for HCC.

Pitfalls, challenges, and updates in adjuvant systemic treatment for resected biliary tract cancer.

Abstract: Introduction: Unfortunately, potentially curative surgical resection is possible in approximately the 25% of biliary tract cancer (BTC) patients at diagnosis, and even following radical surgery, re

BILCAP trial and adjuvant capecitabine in resectable biliary tract cancer: reflections on a standard of care.

Abstract: Biliary tract cancer (BTC) is a heterogeneous group of aggressive malignancies comprising ampulla of Vater cancer, gallbladder cancer, extrahepatic cholangiocarcinoma, and intrahepatic cholangiocarcinoma; unfortunately, the incidence of distant and locoregional recurrence remains high in resected BTCs, with approximately 60-70% of the patients who will experience disease relapse. Until a few years ago, adjuvant treatment was mainly based on the results of a meta-analysis including heterogeneous retrospective studies and showing a survival benefit in the selected populations of resected BTC patients with node-positive disease and/or R1 resection. More recently, the results of several prospective randomized clinical trials have been presented and published. Among these, although the randomized phase III BILCAP trial comparing adjuvant capecitabine versus placebo failed to meet its primary endpoint by intention-to-treat analysis, the preplanned sensitivity analysis highlighted a survival benefit, leading to the wide adoption of capecitabine as adjuvant treatment. However, several unanswered questions remain, including the following: may standard capecitabine represent the effective, real standard of care in this setting? Herein, we discuss the results of the BILCAP study, with a particular focus on the impact the trial had in everyday clinical practice worldwide.

A single-letter change in an acronym: signals, reasons, promises, challenges, and steps ahead for moving from NAFLD to MAFLD.

Abstract: Introduction: We are currently at the dawn of a revolution in the field of fatty liver diseases. Recently, a consensus recommended ‘metabolic (dysfunction) associated fatty liver disease’ (MAFLD) a...

Contrast-enhanced harmonic endoscopic ultrasound-guided fine-needle aspiration versus standard fine-needle aspiration in pancreatic masses: a meta-analysis.

Abstract: It is still unclear whether endoscopic ultrasound (EUS) contrast-enhanced fine-needle aspiration (CH-EUS-FNA) determines superior results in comparison to standard EUS-FNA in tissue acquisition of ...

Angiogenesis in the progression from liver fibrosis to cirrhosis and hepatocelluar carcinoma.

Abstract: Introduction: Persistent inflammation and hypoxia are strong stimulus for pathological angiogenesis and vascular remodeling, and are also the most important elements resulting in liver fibrosis. Sustained inflammatory process stimulates fibrosis to the end-point of cirrhosis and sinusoidal portal hypertension is an important feature of cirrhosis. Neovascularization plays a pivotal role in collateral circulation formation of portal vein, mesenteric congestion, and high perfusion. Imbalance of hepatic artery and portal vein blood flow leads to the increase of hepatic artery inflow, which is beneficial to the formation of nodules. Angiogenesis contributes to progression from liver fibrosis to cirrhosis and hepatocellular carcinoma (HCC) and anti-angiogenesis therapy can improve liver fibrosis, reduce portal pressure, and prolong overall survival of patients with HCC. Areas covers: This paper will try to address the difference of the morphological characteristics and mechanisms of neovascularization in the process from liver fibrosis to cirrhosis and HCC and further compare the different efficacy of anti-angiogenesis therapy in these three stages. Expert opinion: More in-depth understanding of the role of angiogenesis factors and the relationship between angiogenesis and other aspects of the pathogenesis and transformation may be the key to enabling future progress in the treatment of patients with liver fibrosis, cirrhosis, and HCC.

Gastrointestinal involvement of autism spectrum disorder: focus on gut microbiota.

Abstract: Autism spectrum disorder (ASD) is a neurodevelopmental disorder typical of early age, characterized by impaired communication, social interaction, and repetitive behaviors. ASD patients frequently ...

Burden of comorbid anxiety and depression in patients with inflammatory bowel disease: a systematic literature review.

Abstract: INTRODUCTION Patients with inflammatory bowel disease (IBD), including Crohn's disease and ulcerative colitis, often have comorbid anxiety and depression that affects their quality of life (QoL) and management of their IBD. AREAS COVERED A systematic literature review (SLR) was conducted to identify articles and conference abstracts on comorbid anxiety and depression in IBD patients using MEDLINE® and Embase® (January 2003 - June 2018). The impact of these psychological comorbidities on QoL and economic burden was examined. Non-pharmacologic interventions and disease-specific unmet clinical needs associated with these comorbidities were also evaluated. EXPERT OPINION There is evidence that individual and group-based cognitive behavioral therapy can reduce rates of anxiety and depression in adults and adolescents with IBD. Patients with IBD and anxiety or depression had an increased risk of hospitalization, emergency department visits, readmission, and used outpatient services more often than people without these conditions. Several disease-specific unmet clinical needs for IBD patients were identified. These included lack of reimbursement for mental-health care, inconsistent screening for psychological comorbidities and patients not consulting mental-health professionals when needed. IBD patients may benefit from integrated medical and psychological treatment, and should be considered for behavioral treatment.Plain Language Summary. BACKGROUND People with IBD may have mental-health conditions, such as anxiety and depression. These conditions can affect people's quality of life and how they manage their IBD. WHAT DID THIS REVIEW LOOK AT? We found 79 publications on anxiety or depression in people with IBD, published between January 2003 and June 2018. In people with IBD and anxiety or depression, researchers looked at: the impact on health-related quality of life and healthcare utilization, including access to and reimbursement for mental-health services how effective interventions that do not involve the use of medicines were (known as non-pharmacologic therapy). WHAT WERE THE MAIN FINDINGS FROM THIS REVIEW? People with IBD and anxiety or depression were more likely to be admitted to hospital and visit emergency departments than people without these conditions. Access to mental-health care varied and some people with IBD were not screened for depression.Individual and group-based talking therapy (known as cognitive behavioral therapy) reduced rates of anxiety and depression in some people with IBD. WHAT WERE THE MAIN CONCLUSIONS FROM THIS REVIEW? We found evidence that people with IBD and anxiety or depression may benefit from certain non-pharmacologic interventions. However, many people with IBD and anxiety or depression did not have access to mental-health services. Healthcare professionals should address gaps in patient care to improve outcomes in people with IBD and anxiety or depression.See Additional file 1 for an infographic plain language summary.

Gastrointestinal Coronavirus disease 2019: epidemiology, clinical features, pathogenesis, prevention and management

Abstract: The new Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) is the etiologic agent of coronavirus disease 2019. Some authors reported pieces of evidence that patients with SARS-CoV-2 infec...

Capsule endoscopy - Recent developments and future directions.

Abstract: Capsule endoscopy (CE) is an established modality in the diagnostic algorithm of small bowel (SB) pathology. Its use has expanded for investigation of upper and lower gastrointestinal diseases with...

Cross-talk between immune system and microbiota in COVID-19.

Abstract: Introduction Human gut microbiota plays a crucial role in providing protective responses against pathogens, particularly by regulating immune system homeostasis. There is a reciprocal interaction between the gut and lung microbiota, called the gut-lung axis (GLA). Any alteration in the gut microbiota or their metabolites can cause immune dysregulation, which can impair the antiviral activity of the immune system against respiratory viruses such as severe acute respiratory syndrome coronavirus (SARS-CoV) and SARS-CoV-2. Areas covered This narrative review mainly outlines emerging data on the mechanisms underlying the interactions between the immune system and intestinal microbial dysbiosis, which is caused by an imbalance in the levels of essential metabolites. The authors will also discuss the role of probiotics in restoring the balance of the gut microbiota and modulation of cytokine storm. Expert opinion Microbiota-derived signals regulate the immune system and protect different tissues during severe viral respiratory infections. The GLA's equilibration could help manage the mortality and morbidity rates associated with SARS-CoV-2 infection.

Epidemiology, burden of disease, and unmet needs in the treatment of ulcerative colitis in Asia

Abstract: Ulcerative colitis (UC) is an idiopathic, chronic inflammatory disease of the colon, characterized by relapsing and remitting symptoms. Although traditionally viewed as a Western disease, the incid...

Ranson score to stratify severity in Acute Pancreatitis remains valid - Old is gold.

Abstract: Introduction: Acute pancreatitis (AP) is a common gastrointestinal disease with a wide spectrum of severity and associated morbidity. Developed in 1974, the Ranson score was the first scoring system to prognosticate AP. Over the past decades, while the Ranson score remains widely used, it was also identified to have certain limitations, such as having low predictive power. It has also been criticized for its 48-hour requirement for computation of the final score, which has been argued to potentially delay management. With advancements in our understanding of AP, is the Ranson score still relevant as an effective prognostication system for AP?Areas covered: This review summarises the available evidence comparing the Ranson score with other conventional and novel scoring systems, in terms of prognostic accuracy, benefits, limitations and clinical applicability. It also evaluates the effectiveness of the Ranson score with regards to the Revised Atlanta Classification.Expert Opinion: The Ranson score consistently exhibits comparable prognostic accuracy to other newer scoring systems, and the 48-hour timeframe for computing the full Ranson score is an inherent strength, not a weakness. These aspects, coupled with relative ease of use, practicality and universality of the score, advocate for the continued relevance of the Ranson score in modern clinical practice.

An update on the use of immunotherapy in patients with colorectal cancer.

Abstract: Introduction: Colorectal cancer (CRC) is the third most common malignancy worldwide, with recent trends demonstrating increasing incidence amongst younger patients. Despite multiple treatment options, metastatic disease remains incurable. A new therapeutic strategy to harness the host immune system, specifically with immune checkpoint inhibitors, now has reported results from a number of clinical trials. Areas covered: This review will discuss in detail microsatellite instability (MSI) and other biomarkers for response to immunotherapy, summarize the pivotal clinical trials of immune checkpoint inhibitors in early-stage and metastatic MSI colorectal cancer, explore strategies to induce treatment responses in MSS CRC and highlight the emerging treatments and novel immune-based therapies under investigation. Expert opinion: Immunotherapy is now a standard of care for the proportion of CRC patients with MSI. While overall survival data are still awaited, the promise of profound and durable responses is highly anticipated. The lack of efficacy in MSS CRC is disappointing and strategies to convert these 'cold' tumors are needed. Further elucidation of optimal use of treatment sequences, combinations and novel agents will improve outcomes.

Recurrence of hepatocellular carcinoma following liver transplantation

Abstract: Hepatocellular carcinoma (HCC) is an increasingly common disease with liver transplant (LT) the best long-term therapy for early stage disease. We will review the data for assessing risk and managi...

Nivolumab + Ipilimumab for patients with hepatocellular carcinoma previously treated with Sorafenib.

Abstract: The systemic treatment of advanced, unresectable hepatocellular carcinoma (HCC) has undergone an evolution in recent years. In March 2020, a combination of nivolumab and ipilimumab was approved by ...

Chronic liver disease and oxidative stress - a narrative review.

Abstract: Introduction: Oxidative stress underlies the pathophysiology of various etiologies of chronic liver disease and contributes to the development of hepatocarcinogenesis.Areas covered: This review focuses on the impact of oxidative stress in various etiologies of chronic liver disease such as alcoholic liver disease (ALD), nonalcoholic steatohepatitis (NASH), hepatitis B virus (HBV), and hepatitis C virus (HCV) infection. The efficacy of antioxidants in laboratory, animal, and clinical studies in chronic liver disease is also reviewed.Expert opinion: Currently, there are limited targeted pharmacotherapeutics for NASH and no pharmacotherapeutics for ALD and antioxidant supplementation may be useful in these conditions to improve liver function and reverse fibrosis. Antioxidants may also be used in patients with HBV or HCV infection to supplement antiviral therapies. Specific genotypes of antioxidant and prooxidant genes render patients more susceptible to liver cirrhosis and hepatocellular carcinoma while other individual characteristics like age, genotype, and metabolomic profiling can influence the efficacy of antioxidants on CLD. More research needs to be done to establish the safety, efficacy, and dosage of antioxidants and to establish the ideal patient profile that will benefit the most from antioxidant treatment.

The high-dose amoxicillin-proton pump inhibitor dual therapy in eradication of Helicobacter pylori infection.

Abstract: More attention has been paid to the eradication therapy of Helicobactor pylori with the enhancement of health awareness of patients. However, the increasing antibiotic resistance of H. pylori, due ...

Clinical impact of sarcopenia assessment in patients with liver cirrhosis

Abstract: Introduction: Sarcopenia is defined as loss of skeletal muscle mass, strength, and function, and it is associated with increased morbidity and mortality in patients with chronic liver disease.Areas covered: The aim of this review is to provide a detailed report on the pathophysiological mechanisms underlying sarcopenia in cirrhotic patients, the several imaging methods available for the assessment of sarcopenia and the clinical studies evaluating the prognostic role of sarcopenia presence in cirrhotic patients.Expert opinion: Sarcopenia pathogenesis is complex and multifaceted, as chronic catabolic conditions, increased energy expenditure, reduced appetite, side effects of multiple therapies, alterations in circulating levels of hormones, low protein synthesis, presence of ascites or portosystemic shunts are all factors contributing to muscle atrophy in cirrhotic patients. Computed tomography scan is the most validated method to evaluate muscle mass and quality. Sarcopenia is associated with a higher rate waitlist mortality, hepatic encephalopathy, and lower quality of life in patients with liver cirrhosis. Future studies should make an effort to unify and validate liver disease-specific cutoffs for the definition of sarcopenia.

Prevention and Treatment of Stricturing Crohn's Disease - Perspectives and Challenges

Abstract: Introduction: Fibrostenosis is a hallmark of Crohn's disease (CD), remains a challenge in today's clinical management of inflammatory bowel disease patients and represents a key event in the disease course necessitating improved preventative strategies and a multidisciplinary approach to diagnosis and management. With the advent of anti-fibrotic therapies and well-defined clinical endpoints for stricturing CD, there is promise to impact the natural history of disease.Areas covered: This review summarizes current evidence in the natural history of stricturing Crohn's disease, discusses management approaches as well as future perspectives on intestinal fibrosis.Expert opinion: Currently, there are no specific therapies to prevent progression to fibrosis or to treat it after it becomes clinically apparent. In addition to the international effort by the Stenosis Therapy and Anti-Fibrotic Research (STAR) consortium to standardize definitions and propose endpoints in the management of stricturing CD, further research to improve our understanding of mechanisms of intestinal fibrosis will help pave the way for the development of future anti-fibrotic therapies.

Biomarkers of drug-induced liver injury: a mechanistic perspective through acetaminophen hepatotoxicity.

Abstract: Introduction: Liver injury induced by drugs is a serious clinical problem. Many circulating biomarkers for identifying and predicting drug-induced liver injury (DILI) have been proposed.Areas cover...

Do combined assays of serum AFP, AFP-L3, DCP, GP73, and DKK-1 efficiently improve the clinical values of biomarkers in decision-making for hepatocellular carcinoma? A meta-analysis.

Abstract: Objectives: Serum biomarkers are valuable for clinical decision-making for patients with hepatocellular carcinoma (HCC), among which the most promising are AFP, AFP-L3, DCP, DKK-1, and GP73; howeve...

Managing cognitive symptoms and fatigue in cholestatic liver disease.

Abstract: Introduction: Patients with cholestatic diseases may develop fatigue and cognitive symptoms. The impact of symptom burden may be significant in some patients. To date, there are no effective pharmacological therapies to improve cognitive symptoms or fatigue in cholestasis and we are wholly reliant on supportive approaches. Area covered: This review provides an overview of cognitive symptoms and fatigue in the cholestatic liver disease primary biliary cholangitis (PBC), including pathophysiology and our approach to the management of these symptoms. Expert opinion: The impact of fatigue and cognitive symptoms on the perceived quality of life can be profound for patients with PBC. The pathophysiology of these symptoms is complex and poorly understood, making the development of therapeutic trials of symptom-directed therapies challenging. The current recommended management for fatigue and cognitive symptoms is mainly supportive.

Defining the current role of immune checkpoint inhibitors in the treatment of mismatch repair-deficient/microsatellite stability-high colorectal cancer and shedding light on future approaches.

Abstract: Introduction: Mismatch repair deficient (MMR-D)/microsatellite instability-high (MSI-H) colorectal cancer (CRC) carries unique biologic features including high tumor mutation burden, increased amount of mutation-associated neoantigen generation, and the presence of marked tumor-infiltrating lymphocytes Immune checkpoint inhibitor (ICI) therapy has rapidly changed the treatment algorithm of MMR-D/MSI-H CRCAreas covered: In this review article, we discuss the recent data regarding the use of ICIs in metastatic MMR-D/MSI-H CRC patients We also elaborated on potential biomarkers of ICI response and innovative therapeutic approaches that may prevail resistance mechanisms for the treatment of MMR-D/MSI-H colorectal cancerExpert opinion: Pembrolizumab was recently granted approval by the FDA as first-line therapy for metastatic MMR-D/MSI-H CRC based on the results of the Keynote 177 study The combination of nivolumab and ipilimumab will also likely be a choice for the initial therapy of MMR-D/MSI-H CRC in the near future More therapeutic modalities with novel immunomodulatory agents as well as targeted therapy directed to immune resistance pathways are needed The novel approaches discussed in this review article will define potential treatment options for the management of MMR-D/MSI-H CRC patients who progress on first-line ICI therapy

Iron deficiency anemia in IBD: an overlooked comorbidity.

Abstract: Introduction: Iron Deficiency Anemia (IDA) is a leading cause of anemia in Inflammatory Bowel disease (IBD). IDA affects quality of life (QoL) and lead to developmental and cognitive abnormalities....

A comprehensive update on early gastric cancer: defining terms, etiology, and alarming risk factors.

Abstract: Early gastric cancer (EGC) is a well-defined gastric malignancy that is limited to the mucosa or submucosa, irrespective of lymph node metastasis. At an early stage, gastric cancer often does not c...

Patients with inflammatory bowel disease (IBD) prefer oral tablets over other modes of medicine administration.

Abstract: Objectives: With increasing treatment choices for inflammatory bowel disease (IBD), patients’ preferences should be considered to limit non-adherence. We explored patients’ preferences for route, f...

Updates in association of gastroesophageal reflux disease and dental erosion: systematic review.

Abstract: Introduction: Dental erosion occurs by dissolving dental apatite when exposed to non-bacterial acids One of the factors that predispose to dental erosion is gastroesophageal reflux disease (GERD) due to chronic regurgitation of gastric contents to the oropharynx Thus, in addition to other extraesophageal symptoms, individuals with GERD may have erosive dental lesionsAreas covered: The objective of this systematic review was to evaluate the association and prevalence of erosive wear in patients with GERD The bibliographic search was performed in the Pubmed and Web of Science databases, using the descriptors 'gastroesophageal reflux disease' AND 'dental erosion', considering clinical studies recently published from 2012 to 2020Expert opinion: GERD can be considered a risk factor for the development of erosive dental lesions, whose prevalence was significantly higher in this group However, several other factors can be commonly associated with the prevalence and severity of dental erosion among the world population, such as dietary habits, lifestyle, abrasion and bruxism Thus, the prevalence and distribution of erosive lesions among healthy and GERD subjects varied widely among studies, which denotes the etiological complexity of dental erosion and reinforces the importance of careful and detailed anamnesis in order to establish an accurate diagnosis