Objective: The choice of the Helicobacter pylori (H. pylori) eradication regimen should depend on the antibiotic resistance of this major gastric pathogen. In Latvia, resistance patterns of H. pylori strains have not been described in the general population. The aim of the study is to evaluate the primary susceptibility of H. pylori to antibiotics used in recommended eradication regimens for the middle-aged population in Latvia. Materials and Methods: H. pylori antibiotic resistance was assessed in asymptomatic individuals aged 40-64 years, recruited as part of the GISTAR pilot study. H. pylori culture was recovered from initially frozen biopsies taken during the endoscopic examinations. Antimicrobial susceptibility to metronidazole, clarithromycin, amoxicillin, tetracycline, rifampicin, and levofloxacin was successfully determined in 89 isolates using the Epsilomer test (E-test, BioMerieux, France), and interpreted according to EUCAST clinical breakpoint standard. Results: Among the 89 tested isolates, 49 isolates (55%) were resistant to at least one of the tested antibiotics. Resistance to metronidazole was detected in 31 cases (34.8%; 95% CI: 25.2-45.7), followed by rifampicin in nine cases (10.1%; 95% CI: 5.0-18.8%), clarithromycin in five (5.6%; 95% CI: 2.1-13.2) and to levofloxacin in four cases (4.5%; 95% CI: 1.5-11.8). None of the cultures displayed resistance to tetracycline or amoxicillin. Eight resistance patterns were detected: 34 participants had resistance to one of the tested antibiotics; six participants had double resistance, and one participant had resistance to metronidazole, clarithromycin, and levofloxacin. Conclusions: H. pylori’s primary resistance to clarithromycin is still low; therefore, the use of standard clarithromycin-based triple therapies may be justified as the first-line therapy for H. pylori eradication in the middle-aged population in Latvia.

BACKGROUND:Inflammation plays an important albeit dual role in carcinogenesis. Survival studies have highlighted the prognostic significance of peritumorous inflammation. Currently, the theoretical background allows inflammation, epithelial mesenchymal transition (EMT) and the closely associated stem cell differentiation in colorectal carcinoma (CRC) to be linked. However, there is scarce direct morphological evidence. PURPOSE AND METHODS:The aim of our study was to investigate the role of inflammation in cancer growth and invasion by analyzing the association between inflammation and known morphological prognostic features of colorectal cancer, EMT, stemness and mismatch repair (MMR) protein expression. The study was designed as a retrospective morphological and immunohistochemical assessment of 553 consecutive cases of surgically treated primary CRC. RESULTS:There were statistically significant associations between high-grade inflammation and lower pT (p = 0.002), absence of lymph node metastases (p < 0.001) and less frequent lymphatic (p = 0.003), venous (p = 0.017), arterial (p = 0.012), perineural (p = 0.001) and intraneural (p = 0.01) invasion. In contrast, Crohn's like reaction (CLR) by density of lymphoid follicles in the invasive front lacked significant differences in regard to pT, pN, tumor invasion into surrounding structures (blood or lymphatic vessels, nerves), grade or necrosis (all p > 0.05). The expression of E-cadherin, CD44 and MMR proteins yielded no statistically significant associations with peritumorous inflammation by Klintrup-Mäkinen score or the density of lymphoid follicles. Nevertheless, E-cadherin levels were significantly associated with the density of eosinophils (p = 0.007). CONCLUSION:High-grade peritumorous inflammation is associated with beneficial morphologic CRC features, including less frequent manifestations of invasion, and is not secondary to tissue damage and necrosis. CLR is not associated with cancer spread by pTN; this finding indirectly suggests an independent role of CLR in carcinogenesis. Further, inflammation by Klintrup-Mäkinen grade and CLR is not dependent on epithelial-mesenchymal transition and stem cell differentiation. Our study highlights the complex associations between inflammation, tumor morphology, EMT, stemness and MMR protein expression in human CRC tissues.

Abstract Gliomas are among the most common and aggressive primary brain tumours with dismal prognosis. A lot of research has been directed towards elucidating the molecular basis of these tumours, but few reliable prognostic markers are known. It is necessary to continue to study possible molecular factors that may be involved in development of gliomas or have a prognostic role. CD44 is a marker of neural stem cells and is involved in invasiveness of different tumours. In addition, IDH1 R132H mutant protein is expressed in secondary glioblastomas (GBMs) with much better prognosis. The goal of this study was to evaluate the expression and prognostic role of CD44 and IDH1 R132H in gliomas by immunohistochemistry. In this study, we found that CD44 expression was more prominent in glioblastomas than diffuse astrocytomas and it was not correlated with IDH1 mutational status. CD44 was not found to have a prognostic role in gliomas, in contrast with IDH1 R132H positive status, which was associated with better prognosis. Interestingly, higher CD44 expression values were associated with smaller size of GBMs and female gender indicating that the glioma stem cell population may be altered by gender specific factors and the growth rate of the tumour.

Background. Colorectal cancer (CRC) is the third most common cancer in the world. The cornerstone of CRC treatment is surgical resection. However, patients in the same TNM stage show different recurrence rates and survival. Of patients with a local disease without lymph node or a distant metastasis, 20–25% still develop recurrence. There is evidence that inflammatory reaction is one of the key elements in tumour development. Materials and methods. We reviewed literature on colorectal cancer and its relationships with the immune system, with special focus on local and systemic inflammatory reaction. The Pubmed and ClinicalKey databases were searched using the key words colorectal cancer, local inflammation, systemic inflammation, markers of inflammation. The relevant literature was reviewed and included in the article. Results. The immune system has two-sided relationships with cancer, so it not only performs anti-tumour activities, but can also promote tumour growth and spread. Research has shown that signs of local inflammation are associated with a better prognosis in CRC. Systemic inflammation has been associated with more aggressive behaviour and a worse prognosis for patients with several cancers, including CRC. Conclusions. Recent findings in tumour biology have improved our understanding of colorectal cancer and of the natural course of this disease. Several markers of local and systemic inflammatory reaction have been identified. The next step is to find the most accurate and applicable marker, so that this promising tool can be used in clinical practice and aid in decision making.

In this study we assessed whether gliomas could be subdivided into different molecular subtypes by immunohistochemistry (IHC) reminiscent of those first described by Verhaak et al. in 2010 (classical, proneural, mesenchymal and neural). We also evaluated the prognostic significance of single molecular factors and searched for significant correlations between markers. In this study, we included 146 patients with glioblastomas (GBMs) and 26 with diffuse astrocytomas (DAs). The glioma samples were tested for PDGFRA, IDH1 R132H, CD44, p53, Ki-67, p21 and p27 expression. We found that gliomas could be subdivided into molecular subtypes by IHC. Fifty per cent of GBMs were of the proneural subtype, 18.5% of mesenchymal subtype and 31.5% were not otherwise classified. However, most of the DAs (92.3%) belonged to the proneural subtype. No prognostic role was found for the molecular subtypes, but predictive roles were noted. Both proneural and mesenchymal molecular subtypes showed a benefit from the addition of chemotherapy and radiotherapy; however, the mesenchymal subtype showed a greater response. Interestingly, the mesenchymal subtype did not receive any benefit from the addition of radiotherapy compared with palliative management and surgery alone. Regarding single molecular markers, only IDH1 R132H was found to have a prognostic role for GBMs. There was a trend towards better survival in tumours with lower PDGFRA expression (p = 0.066). In DAs, PDGFRA and Ki-67 expression had prognostic roles. The following statistically significant correlations were found in GBMs: Ki-67/p53, Ki-67/p27 and p53/PDGFRA; in DAs: p53/PDGFRA, CD44/PDGFRA, and p21/PDGFRA.

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.

Thyroid cancer is a comparatively rare tumor, which affects 1–5% of women and approximately 2% of men, although it is the most common endocrine malignancy worldwide. Furthermore, the incidence of thyroid cancer has been increasing remarkably in the last decades. Currently, diagnosis of thyroid cancer mainly is based on cytological criteria. Although fine needle aspiration is a minimally invasive procedure, complications can occur. Correct diagnosis is mandatory to select patients for surgical intervention and to determine appropriate extent of operation. Overdiagnosis and the associated unnecessary surgery should be avoided as it might also lead to complications. Therefore it is important to practice noninvasive methods not only for early diagnosis of thyroid cancer but also for estimation of prognosis. Liquid biopsy is a promising, noninvasive method that can provide detection of circulating tumor cells (CTCs) as well as circulating nucleic acids such as DNA, mRNA, and microRNA in a blood sample. The aim of the chapter is to highlight the efficacy of liquid biopsy for diagnosis and prognosis of thyroid cancer. The chapter will represent a comprehensive literature review based on recent PubMed publications (mainly 2012–2018).

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.

Pancreatic ductal adenocarcinoma induces systemic inflammatory response (SIR), which can be assessed either by ratios between blood cell counts (neutrophil to lymphocyte ratio, NLR; platelet to lymphocyte ratio, PLR) or concentrations of acute phase proteins, clotting factors and albumins.These tests are biologically justified by multiple 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 assessment of SIR is widely available, patient-friendly and economically feasible.In this chapter, we present a review on NLR, PLR, Glasgow prognostic score and fibrinogen, recently reported to have a prognostic role regarding overall survival, cancer/progression free and cancer-specific survival in early and advanced pancreatic ductal adenocarcinoma.Practical consequences abound, including preference for surgical or combined, active or sparing treatment, as well as prediction of non-resectability or chemotherapy response.In this chapter, we also scrutinise the main controversies including different cut-off levels, hypothetic correlation with tumour burden and morphology, negative findings and discussions on the best marker.Future developments should include elaboration of complex scores as will be described here.

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.

Thyroid nodules are frequent in general population, found in 3.7–7% of people by palpation and 42–67% by ultrasonography (US). The differential diagnosis ranges from papillary (PC), follicular (FC) and medullary (MC) carcinomas to follicular adenoma (FA) and colloid goitre. Cancer risk in thyroid nodules varies: 5% in masses found by palpation, 1.6–15% by US, 3.9–11.3% by computed tomography (CT), 5–6% by magnetic resonance imaging (MRI) and 30–50% by positron emission tomography (PET). The final diagnosis depends on fine needle aspiration (FNA) findings and histopathology. The recent WHO classification (2017) is based on classic morphology, including assessment of invasion and nuclei. New entities are defined to designate tumours with doubtful invasion or controversial nuclear features. By immunohistochemistry, PC expresses HBME-1, TROP2, CITED1 and CK19. Notably, PC can stain for CD20. MC is recognised by neuroendocrine differentiation. To distinguish FA vs. FC, evaluation of HBME-1, p27 and galectin has been suggested. Regarding miRNAs, miR-146b, miR-222, miR-221 and miR-181b are upregulated, while miR-145, miR-451, miR-613 and miR-137 are downregulated in PC. FC features downregulated miR-199a-5p and upregulated miR-197 and miR-346. In MC, miR-21 and miR-129-5p are downregulated. In addition, increased systemic inflammatory reaction can be poor prognostic factor in thyroid cancer. The aim of this chapter is to review classic and innovative histopathology of thyroid nodules for diagnostic pathology practice and research in multidisciplinary thyroid teams.

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.

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.