Dzeina Mezale

By Dzeina Mezale, Ilze Strumfa, Andrejs Vanags, Matiss Mezals, Ilze Fridrihsone, Boriss Strumfs and Dainis Balodis

Non-alcoholic steatohepatitis (NASH) is growing into global problem, mainly due to NASH-induced cirrhosis and hepatocellular carcinoma (HCC), that can develop either subsequently to cirrhosis or preceding it. In addition, NASH-induced cirrhosis constitutes a significant fraction of cases diagnosed as cryptogenic cirrhosis. Thus, there is a need for deeper understanding of the molecular basis, leading to liver steatosis, then—to the associated inflammation seen in NASH, loss of liver architecture and cirrhosis, followed or paralleled by carcinogenesis and HCC. Insulin resistance, increased hepatic iron level, and certain cytokines, including TNF-α and IL-6 derived from extrahepatic adipose tissues, can trigger the chain of events. The imbalance between leptin and adiponectin is important as well. These markers remain important during the whole course from NASH through liver cirrhosis to HCC. The molecular pathogenesis substantiates treatment: hypertriglyceridemia can be lowered by low calorie diet; mTOR complex can become inhibited by physical activity and metformin; cholesterol synthesis, RAF/MAPK1/ERK and p21 pathway by statins; inflammation by pentoxyfillin, and kinases (in HCC) by sorafenib. Bidirectional regulation of telomere attrition, senescence and p21 pathway, restoration of wild-type p53 activity and regulation of miRNA network represent attractive future treatment options. Focusing on relevant molecular pathways allows deeper understanding of NASH pathogenesis, leading to identification of predictive markers and treatment targets.

Part of the book: Liver Cirrhosis

By Ilze Strumfa, Tatjana Bogdanova, Arturs Kalva, Boriss Strumfs, Roberts Rumba, Andrejs Vanags, Inese Drike, Dzeina Mezale, Arnis Abolins, Arvids Jakovlevs, Dainis Balodis and Janis Gardovskis

Gastric cancer induces systemic inflammatory reaction (SIR) manifesting with changes in counts of white blood cell fractions and concentrations of acute phase proteins, clotting factors and albumins. Thus, protein-based scores or blood cell ratios (neutrophil to lymphocyte ratio (NLR); platelet to lymphocyte ratio (PLR)) are used to evaluate SIR. SIR tests are biologically justified by multiple clinically important and fascinating events including bone marrow activation, development of immune-suppressing immature myeloid cells, generation of pre-metastatic niches and neutrophil extracellular trap formation from externalised DNA network in bidirectional association with platelet activation. Despite biological complexity, clinical SIR assessment is widely available, patient-friendly and economically feasible. Here we present concise review on NLR, PLR, Glasgow prognostic score and fibrinogen – parameters that have prognostic role regarding overall, cancer-free and cancer-specific survival in early and advanced cases. Tumour burden can be predicted helping in preoperative detection of serosal or lymph node involvement. Practical consequences abound, including selection of surgical approach in respect to tumour burden, adjustments in treatment intensity by prognosis or evaluation of chemotherapy response. The chapter also scrutinises main controversies including different cut-off levels. Future developments should include elaboration of complex scores as described here. SIR parameters should be wisely incorporated in patients’ treatment.

Part of the book: Gastric Cancer

By Roberts Rumba, Andrejs Vanags, Arturs Kalva, Tatjana Bogdanova, Inese Drike, Dzeina Mezale, Marta Vitola, Janis Gardovskis and Ilze Strumfa

Gastric cancer is one of the most common gastrointestinal malignancies, known also for its dismal prognosis, except early cases. Despite the advances in systemic therapy, surgery remains the cornerstone of treatment. The majority of gastric cancers are carcinomas, while neuroendocrine tumours and gastrointestinal stromal tumours (GISTs) rank next by frequency. Tumour biology, disease course and prognosis differ amongst the aforementioned gastric cancers; thus, surgical treatment has to be adjusted as well. Accumulation of evidence ensures an individualised approach in all aspects of surgical treatment. Specific criteria are set to choose the best surgical treatment while maintaining postoperative function and acceptable life quality. Minimally invasive techniques continue to gain acceptance, while usage is still highly variable. Endoscopic resection is suitable for very early adenocarcinomas, whereas more advanced tumours require standard gastrectomy. Despite the initial concerns, subtotal gastrectomy (SG) is feasible and safe, especially for distal adenocarcinomas. In recent years, D2 lymphadenectomies have become more frequent in Western countries, and evidence supports this tendency. Surgery for gastric neuroendocrine tumours is type-specific and will be discussed in detail. Gastrointestinal stromal tumours are treated by local resection without wide margins or extensive lymph node dissection. Novel targeted therapy can aid surgical treatment by downstaging larger GISTs.

Part of the book: Gastric Cancer

By Dzeina Mezale, Ilze Strumfa, Andrejs Vanags, Arturs Kalva, Dainis Balodis, Boriss Strumfs, Ilze Fridrihsone, Arnis Abolins and Janis Gardovskis

In the global cancer statistics, hepatocellular carcinoma (HCC) ranges sixth by incidence and second by oncological mortality. The risk factors comprise hepatitis B and C virus infection, non-alcoholic steatohepatitis, as well as long-lasting peroral exposure to alcohol or aflatoxins. Liver cirrhosis is the most important single predisposing factor. Ultrasonography once per 6 months is recommended for surveillance in cirrhotic patients. Computed tomography (CT) and magnetic resonance imaging (MRI) represent the gold standard of non-invasive diagnostics while core biopsy and/or immunohistochemistry (IHC) are indicated for controversial and non-cirrhotic HCC cases. Molecular classification is under development. At present, classics of HCC diagnostics is based on evaluation of risk factors, surveillance in cirrhotic patients, preference for CT or MRI-confirmed non-invasive diagnosis and biopsy proof in equivocal cases. Diffusion-weighted imaging and hepatobiliary phase contrasting represent significant recent developments in MRI. Contrast-enhanced ultrasonography is recommended by some but not all guidelines. Positron emission tomography is advocated before liver transplantation to detect extrahepatic metastases but has limited role in the initial diagnostic evaluation of liver nodule. Innovations are expected in the field of molecular diagnostics, including IHC panels and novel antigens, e.g. clathrin and bile salt export pump protein, and development of molecular classification.

Part of the book: Hepatocellular Carcinoma

By Dzeina Mezale, Ilze Strumfa, Andrejs Vanags, Guntis Bahs, Boriss Strumfs, Arturs Silovs, Reinis Riekstins and Janis Gardovskis

Mucinous cystic neoplasms of the liver and extrahepatic biliary tree have recently been re-defined by WHO as epithelial cystic tumours with ovarian-type mesenchymal stroma. Correct recognition of these tumours can be difficult because of their rarity and, consequently, lack of awareness by the medical team. Radiological evaluation, including ultrasonography, computed tomography, magnetic resonance imaging and, upon necessity, positron emission tomography, can yield the correct diagnosis. Radical surgical resection with tumour-free margins is the mainstay of treatment. Adequate treatment approach can be very rewarding, bringing prolonged survival. Here we discuss the up-to-date concepts of definition and classification, theoretical views on tumour origin along with practical issues of clinical presentation, diagnostics, treatment and prognosis.

Part of the book: Topics in the Surgery of the Biliary Tree

By Ilze Strumfa, Dzeina Mezale, Boriss Strumfs, Andrejs Vanags, Arturs Kalva, Dainis Balodis, Ilze Fridrihsone, Arnis Abolins and Janis Gardovskis

Hepatocellular carcinoma (HCC) is an aggressive tumour associated with dismal prognosis. To improve the outcome, early diagnostics is important. At present, classical HCC diagnostics is based on evaluation of risk factors, surveillance in cirrhotic patients, preference for non-invasive diagnosis by computed tomography or magnetic resonance imaging and biopsy confirmation in controversial cases. However, ambiguous radiological presentation, biopsy-related complications or insufficient representation of the pathology in the tissue core are well-known problems. Panel assessment of microRNAs has diagnostic and prognostic value; thus, in future, microRNA-based liquid biopsy could partially reduce the need for core biopsies. Systemic inflammatory reaction (SIR), characterised mainly by neutrophil-to-lymphocyte ratio, platelet-to-lymphocyte ratio and Glasgow prognostic score, may have prognostic value and can be incorporated in criteria for certain treatment approaches, e.g., becoming an adjunct to Milan criteria. Thus, innovations in HCC diagnostics are expected in the field of miRNA-based liquid biopsy for diagnosis/prognosis and SIR for prognosis/selection of treatment.

Part of the book: Hepatocellular Carcinoma

By Arets Paeglis, Boriss Strumfs, Dzeina Mezale and Ilze Fridrihsone

For more than a decade, machine learning (ML) and deep learning (DL) techniques have been a mainstay in the toolset for the analysis of large amounts of weakly correlated or high-dimensional data. As new technologies for detecting and measuring biochemical markers from bodily fluid samples (e.g., microfluidics and labs-on-a-chip) revolutionise the industry of diagnostics and precision medicine, the heterogeneity and complexity of the acquired data present a growing challenge to their interpretation and usage. In this chapter, we attempt to review the state of ML and DL fields as applied to the analysis of liquid biopsy data and summarise the available corpus of techniques and methodologies.

Part of the book: Liquid Biopsy