Genetic screening of liver cancer: State of the art.

Liver cancer, primarily hepatocellular carcinoma, remains a global health challenge with rising incidence and limited therapeutic options. Genetic factors play a pivotal role in the development and progression of liver cancer. This state-of-the-art paper provides a comprehensive review of the current landscape of genetic screening strategies for liver cancer. We discuss the genetic underpinnings of liver cancer, emphasizing the critical role of risk-associated genetic variants, somatic mutations, and epigenetic alterations. We also explore the intricate interplay between environmental factors and genetics, highlighting how genetic screening can aid in risk stratification and early detection via using liquid biopsy, and advancements in high-throughput sequencing technologies. By synthesizing the latest research findings, we aim to provide a comprehensive overview of the state-of-the-art genetic screening methods for liver cancer, shedding light on their potential to revolutionize early detection, risk assessment, and targeted therapies in the fight against this devastating disease.

New strategies in the diagnosis and treatment of immune-checkpoint inhibitor-mediated colitis.

Immune-checkpoint inhibitor-mediated colitis (IMC) is an increasingly recognized adverse event in cancer immunotherapy, particularly associated with immune checkpoint inhibitors (ICIs) such as anti-cytotoxic T-lymphocyte antigen-4 and anti-programmed cell death protein-1 antibodies. As this revolutionary immunotherapy gains prominence in cancer treatment, understanding, diagnosing, and effectively managing IMC becomes paramount. IMC represents a unique challenge due to its immune-mediated nature and potential for severe complications. However, a precise picture of IMC pathophysiology is currently unavailable. Therefore, we aimed to summarize the existing data while acknowledging the need for further research. This comprehensive review explores the mechanisms underlying ICIs, gastrointestinal adverse effects, and, in particular, IMC's incidence, prevalence, and features. Our review also emphasizes the importance of recognizing IMC's distinct clinical and histopathological features to differentiate it from other forms of colitis. Furthermore, this paper highlights the urgent need for evolving diagnostic methods, therapeutic strategies, and a multidisciplinary approach to effectively manage IMC.

Long-term effectiveness, outcomes and complications of bariatric surgery.

Dietary imbalance and overeating can lead to an increasingly widespread disease - obesity. Aesthetic considerations aside, obesity is defined as an excess of adipose tissue that can lead to serious health problems and can predispose to a number of pathological changes and clinical diseases, including diabetes; hypertension; atherosclerosis; coronary artery disease and stroke; obstructive sleep apnea; depression; weight-related arthropathies and endometrial and breast cancer. A body weight 20% above ideal for age, gender and height is a severe health risk. Bariatric surgery is a set of surgical methods to treat morbid obesity when other treatments such as diet, increased physical activity, behavioral changes and drugs have failed. The two most common procedures currently used are sleeve gastrectomy and gastric bypass. This procedure has gained popularity recently and is generally considered safe and effective. Although current data show that perioperative mortality is low and better control of comorbidities and short-term complications is achieved, more randomized trials are needed to evaluate the long-term outcomes of bariatric procedures. This review aims to synthesize and summarize the growing evidence on the long-term effectiveness, outcomes and complications of bariatric surgery.

Synchronous manifestation of colorectal cancer and intraductal papillary mucinous neoplasms.

High rates of extrapancreatic malignancies, in particular colorectal cancer (CRC), have been detected in patients with intraductal papillary mucinous neoplasm (IPMN). So far, there is no distinct explanation in the literature for the development of secondary or synchronous malignancies in patients with IPMN. In the past few years, some data related to common genetic alterations in IPMN and other affiliated cancers have been published. This review elucidated the association between IPMN and CRC, shedding light on the most relevant genetic alterations that may explain the possible relationship between these entities. In keeping with our findings, we suggested that once the diagnosis of IPMN is made, special consideration of CRC should be undertaken. Presently, there are no specific guidelines regarding colorectal screening programs for patients with IPMN. We recommend that patients with IPMNs are at high-risk for CRC, and a more rigorous colorectal surveillance program should be implemented.

Gut Microbiome Composition and Its Metabolites Are a Key Regulating Factor for Malignant Transformation, Metastasis and Antitumor Immunity.

The genetic and metabolomic abundance of the microbiome exemplifies that the microbiome comprises a more extensive set of genes than the entire human genome, which justifies the numerous metabolic and immunological interactions between the gut microbiota, macroorganisms and immune processes. These interactions have local and systemic impacts that can influence the pathological process of carcinogenesis. The latter can be promoted, enhanced or inhibited by the interactions between the microbiota and the host. This review aimed to present evidence that interactions between the host and the gut microbiota might be a significant exogenic factor for cancer predisposition. It is beyond doubt that the cross-talk between microbiota and the host cells in terms of epigenetic modifications can regulate gene expression patterns and influence cell fate in both beneficial and adverse directions for the host's health. Furthermore, bacterial metabolites could shift pro- and anti-tumor processes in one direction or another. However, the exact mechanisms behind these interactions are elusive and require large-scale omics studies to better understand and possibly discover new therapeutic approaches for cancer.

Specific Immunoglobulin E and G to Common Food Antigens and Increased Serum Zonulin in IBS Patients: A Single-Center Bulgarian Study.

Irritable bowel syndrome (IBS) is a common functional gastrointestinal disorder whose pathogenesis is considered multifactorial, including abnormal gut motility, visceral hyperreactivity, psychological factors, disturbances in the brain-gut axis, leaky gut, oxidative stress, etc. We aimed to investigate serum levels of specific immunoglobulin E and G to common food antigens and zonulin and to assess their use in clinical practice for patients with IBS. Material and methods. We included 23 participants, 15 with IBS (diagnosed according to the Rome IV criteria) and 8 healthy controls. We investigated serum levels of specific IgG antibodies to 24 food antigens, specific IgE antibodies to 20 food antigens, anti-celiac antibodies, fecal calprotectin and serum zonulin by ELISA. Results. Food-specific positive IgG antibodies were significantly higher in patients with IBS than in controls (p = 0.007). IgE-mediated allergic reactions were found in five patients with IBS; no one had anti-TG antibodies. One-third of IBS patients demonstrated a low degree of chronic inflammation (positive fecal calprotectin test > 50 ng/mL) without specific bacterial infection. Serum levels of zonulin in IBS patients were higher than in healthy controls (0.378 ± 0.13 vs. 0.250 ± 0.14 ng/mL, p = 0.0315). However, no correlations between clinical symptoms and zonulin levels were found. Conclusion. The mechanisms of IgG hypersensitivity and low degree inflammation in IBS and elevated zonulin may contribute to multifactor pathogenesis in IBS.

Factors affecting complications development and mortality after single lung transplant.

Lung transplantation (LT) is a life-saving therapeutic procedure that prolongs survival in patients with end-stage lung disease. Furthermore, as a therapeutic option for high-risk candidates, single LT (SLT) can be feasible because the immediate morbidity and mortality after transplantation are lower compared to sequential single (double) LT (SSLTx). Still, the long-term overall survival is, in general, better for SSLTx. Despite the great success over the years, the early post-SLT period remains a perilous time for these patients. Patients who undergo SLT are predisposed to evolving early or late postoperative complications. This review emphasizes factors leading to post-SLT complications in the early and late periods including primary graft dysfunction and chronic lung allograft dysfunction, native lung complications, anastomosis complications, infections, cardiovascular, gastrointestinal, renal, and metabolite complications, and their association with morbidity and mortality in these patients. Furthermore, we discuss the incidence of malignancy after SLT and their correlation with immunosuppression therapy.

Antibiotic-Related Changes in Microbiome: The Hidden Villain behind Colorectal Carcinoma Immunotherapy Failure.

The interplay between drugs and microbiota is critical for successful treatment. An accumulating amount of evidence has identified the significant impact of intestinal microbiota composition on cancer treatment response, particularly immunotherapy. The possible molecular pathways of the interaction between immune checkpoint inhibitors (ICIs) and the microbiome can be used to reverse immunotherapy tolerance in cancer by using various kinds of interventions on the intestinal bacteria. This paper aimed to review the data available on how the antibiotic-related changes in human microbiota during colorectal cancer (CRC) treatment can affect and determine ICI treatment outcomes. We also covered the data that support the potential intimate mechanisms of both local and systemic immune responses induced by changes in the intestinal microbiota. However, further better-powered studies are needed to thoroughly assess the clinical significance of antibiotic-induced alteration of the gut microbiota and its impact on CRC treatment by direct observations of patients receiving antibiotic treatment.

What could microRNA expression tell us more about colorectal serrated pathway carcinogenesis?

In the last two decades, the vision of a unique carcinogenesis model for colorectal carcinoma (CRC) has completely changed. In addition to the adenoma to carcinoma transition, colorectal carcinogenesis can also occur via the serrated pathway. Small non-coding RNA, known as microRNAs (miRNAs), were also shown to be involved in progression towards malignancy. Furthermore, increased expression of certain miRNAs in premalignant sessile serrated lesions (SSLs) was found, emphasizing their role in the serrated pathway progression towards colon cancer. Since miRNAs function as post-transcriptional gene regulators, they have enormous potential to be used as useful biomarkers for CRC and screening in patients with SSLs particularly. In this review, we have summarized the most relevant information about the specific role of miRNAs and their relevant signaling pathways among different serrated lesions and polyps as well as in serrated adenocarcinoma. Additional focus is put on the correlation between gut immunity and miRNA expression in the serrated pathway, which remains unstudied.

ABO-nonidentical liver transplantation from a deceased donor and clinical outcomes following antibody rebound: A case report.

BACKGROUND: Although ABO-nonidentical and ABO-incompatible liver transplantation (LT) are other options for end-stage liver disease treatment, the development of antibodies against blood group antigens (anti-A/B antibodies) is still a challenge in managing and follow-up of the recipients. CASE SUMMARY: A 56-year-old male with end-stage liver disease with rapid deterioration and poor prognosis was considered to receive a deceased ABO-nonidentical liver graft. All required tests were performed according to our pre-LT diagnostic protocol. The orthotopic LT procedure involving O+ donor and A1B+ recipient was performed. Our treatment strategy to overcome the antibody-mediated rejection included a systemic triple immunosuppressive regimen: methylprednisolone, mycophenolate mofetil, and tacrolimus. The immunological desensitization consisted of the chimeric anti-CD20 monoclonal antibody rituximab and intravenous immunoglobulins. The patient was also on antibiotic treatment with amoxicillin/clavulanate, cefotaxime, and metronidazole. On the 10th postoperative day, high titers of IgG anti-A and anti-B antibodies were found in the patient's plasma. We performed a liver biopsy, which revealed histological evidence of antibody-mediated rejection, but the rejection was excluded according to the Banff classification. The therapy was continued until the titer decreased significantly on the 18th postoperative day. Despite the antibiotic, antifungal, and antiviral treatment, the patient deteriorated and developed septic shock with anuria and pancytopenia. The conservative treatment was unsuccessful, which lead to the patient's fatal outcome on the 42nd postoperative day. CONCLUSION: We present a patient who underwent ABO-nonidentical LT from a deceased donor. Even though we implemented the latest technological advancements and therapeutic approaches in the management of the patient and the initial results were promising, due to severe infectious complications, the outcome was fatal.

Surveilling Russell body Helicobacter pylori-negative gastritis: A case report and review of literature.

BACKGROUND: Russell body gastritis (RBG) is very rare type of chronic inflammation of gastric mucosa. The pathologic hallmark of the disease is Russell bodies (RB) which represent accumulation of eosinophilic cytoplasmic inclusions in endoplasmic reticulum of mature plasma cells (Mott cells). Most published cases are associated with Helicobacter pylori (H. pylori) infection because of correlation between plasma cell activation and antigenic stimulation. There are insufficient data about H. pylori-negative RBG and very little is known about the natural course of the disease. CASE SUMMARY: A 51-year-old male patient underwent endoscopic screening for mild iron deficiency anemia. Gastroscopy revealed diffuse hyperemia, edema and nodularity of the fundic and corpus mucosa. Due to non-specific endoscopic findings and iron-deficiency anemia our preliminary diagnosis was diffuse type of gastric carcinoma or gastric lymphoma. Biopsy specimens of gastric mucosa showed inflammatory infiltrate rich in Mott cells, consisting entirely of cytoplasmic RB. Absence of nuclear atypia and mitosis of the plasma cells, polyclonal pattern of the Mott cells and negative staining for cytokeratins favored diagnosis of RBG. The patient was treated with proton-pump inhibitor for 8 wk. Long-term clinical and endoscopic surveillance was scheduled. Albeit, there was no improvement in endoscopic features of the gastric mucosa in three consecutive gastroscopies, histopathological findings demonstrated that the chronic inflammatory infiltrate in the fundic mucosa is less pronounced, rich in plasma cells, with almost absent RB and Mott cells. CONCLUSION: The prognosis of this entity is uncertain, that is why these patients are subjects of continuous follow up.