Helicobacter pylori patří stále mezi celosvětově nejčastější bakteriální infekce, a to i přes pokles v posledních čtyřech dekádách (v současné době činí cca 40–50 %). Infekce je častější v rozvojových zemích ve srovnání se zeměmi vyspělými. Intenzivní výzkum této chronické infekce objasnil patogenezi řady chorob žaludku i onemocnění extragastrických, včetně karcinomu. Tento článek přináší přehled poznatků o roli Helicobacter pylori u různých maligních chorob žaludku. Chronická infekce Helicobacter pylori je etiologickým faktorem karcinomu žaludku distálně od kardie (non-cardia gastric cancer) a většiny případů žaludečního MALT-lymfomu nízkého stupně. Byla ale popsána inverzní asociace helikobakterové infekce s ostatními žaludečními malignitami, jako jsou karcinom kardie nebo vzácný hereditární syndrom GAPPS (gastric adenocarcinoma and proximal polyposis of the stomach). Dosud nebyla definitivně zodpovězena klíčová otázka, zda časná eradikace infekce Helicobacter pylori je účinnou prevencí vzniku karcinomu žaludku v budoucnosti. S jistou mírou spolehlivosti je možno konstatovat, že cílené vyšetřování a eradikace Helicobacter pylori snižuje incidenci a mortalitu karcinomu žaludku asijské populace. Tato zjištění dosud nelze beze zbytku aplikovat na populaci evropskou nebo americkou. Indikace eradikace Helicobacter pylori musí být zvažována uvážlivě, v souladu s principy personalizované medicíny.

Helicobacter pylori belongs to the most common bacterial infections worldwide; despite its decreasing prevalence during the past four decades (currently ~ 40–50%), it is more prevalent in developing countries compared to developed ones. Intensive research of chronic Helicobacter pylori infection clarified the pathogenesis of several gastric and extragastric diseases, including different cancers. This review pointed out the role of Helicobacter pylori in different gastric malignancies. Chronic Helicobacter pylori infection is an etiological factor in non--cardia gastric cancer and most cases of low-grade MALT lymphoma of the stomach. However, there is an inverse association of Helicobacter pylori infection with other gastric malignancies, like cardia gastric cancer or rare hereditary Gastric Adenocarcinoma and Proximal Polyposis of the Stomach syndrome (GAPPS). A crucial issue has not been definitely solved yet: whether early eradication of Helicobacter pylori could prevent sporadic gastric cancer in the future? There is moderate evidence that searching for and eradicating Helicobacter pylori reduces the incidence of gastric cancer and death from gastric cancer in healthy asymptomatic infected Asian individuals, although data cannot necessarily be extrapolated to European or US populations so far. Indication for the eradication of Helicobacter pylori must now be considered with caution, on an individual basis of personalized medicine.

• MeSH
• Helicobacter pylori * patogenita   MeSH
• infekce vyvolané Helicobacter pylori epidemiologie   farmakoterapie   komplikace   MeSH
• lidé MeSH
• lymfom z B-buněk marginální zóny etiologie   patologie   MeSH
• nádory žaludku * etiologie   patologie   prevence a kontrola   MeSH
• rizikové faktory MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• práce podpořená grantem MeSH
• přehledy MeSH

BACKGROUND: Glomus tumors (GTs) are mesenchymal neoplasms that are typically benign. Gastric GTs are uncommon and occur mainly in the upper gastrointestinal tract. Malignant gastric GTs are extremely rare, constituting less than 1% of gastric tumors. Because their features are similar to those of other tumors found in the same gastrointestinal region, such as stromal tumors, leiomyomas, lymphomas, and lipomas, the diagnosis is challenging. CASE PRESENTATION: A 52-year-old male patient presented with fatigue and melena. The initial endoscopic examination did not locate any source of bleeding. Six months later, pan-gastroscopy, performed due to progressive microcytic anemia, revealed a 40 × 30 mm polypoid lesion with deep ulcerations; histopathological analysis confirmed that it was a gastric GT with expression of alpha-actin and cadherin 17 and a Ki-67 index of 20%. The patient delayed surgical therapy until his symptoms worsened. Laparoscopic sleeve resection revealed a 65 × 45 × 25 mm tumor, and secondary immunohistochemical analysis revealed extensive spread into the mucosa and subserosa. Focally, the tumor bulged into some large veins. Genetic examination with RNA isolation further supported the histopathological diagnosis of gastric GT with uncertain malignant potential. CONCLUSIONS: This case underscores the diagnostic challenges posed by gastric GTs because they are rare and their clinical features are similar to those of other gastric tumors. Thorough histopathological and molecular analysis is essential for an accurate diagnosis. Surgical intervention remains the primary therapeutic approach. This case also emphasizes the need for long-term follow-up due to the potential for recurrence and malignancy.

• MeSH
• gastrointestinální krvácení * etiologie   chirurgie   patologie   MeSH
• gastroskopie MeSH
• glomangiom * patologie   chirurgie   komplikace   diagnóza   MeSH
• lidé středního věku MeSH
• lidé MeSH
• nádory žaludku * patologie   komplikace   chirurgie   MeSH
• prognóza MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• kazuistiky MeSH

The asymmetrical distribution of the cellular organelles inside the cell is maintained by a group of cell polarity proteins. The maintenance of polarity is one of the vital host defense mechanisms against pathogens, and the loss of it contributes to infection facilitation and cancer progression. Studies have suggested that infection of viruses and bacteria alters cell polarity. Helicobacter pylori and Epstein-Barr virus are group I carcinogens involved in the progression of multiple clinical conditions besides gastric cancer (GC) and Burkitt's lymphoma, respectively. Moreover, the coinfection of both these pathogens contributes to a highly aggressive form of GC. H. pylori and EBV target the host cell polarity complexes for their pathogenesis. H. pylori-associated proteins like CagA, VacA OipA, and urease were shown to imbalance the cellular homeostasis by altering the cell polarity. Similarly, EBV-associated genes LMP1, LMP2A, LMP2B, EBNA3C, and EBNA1 also contribute to altered cell asymmetry. This review summarized all the possible mechanisms involved in cell polarity deformation in H. pylori and EBV-infected epithelial cells. We have also discussed deregulated molecular pathways like NF-κB, TGF-β/SMAD, and β-catenin in H. pylori, EBV, and their coinfection that further modulate PAR, SCRIB, or CRB polarity complexes in epithelial cells.

• MeSH
• Helicobacter pylori * genetika   MeSH
• infekce virem Epsteina-Barrové * mikrobiologie   patologie   MeSH
• infekce vyvolané Helicobacter pylori * mikrobiologie   MeSH
• koinfekce * mikrobiologie   MeSH
• lidé MeSH
• nádory žaludku * genetika   mikrobiologie   patologie   MeSH
• polarita buněk MeSH
• virové proteiny MeSH
• virus Epsteinův-Barrové genetika   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH

Východiska: V literatuře nejsou žádné zmínky o souběžné chemoradioterapii při karcinomu žaludku s peritoneálními oligometastázami. Popis případu: Muž ve věku 70 let s karcinomem žaludku a peritoneálními oligometastázami byl léčen adaptivní radioterapií a souběžně perorálně podávaným S-1. Po radioterapii bylo podávání S-1 přerušeno a o 2 roky později byla zaznamenána kompletní regrese tumoru bez rekurence metastáz v průběhu 6 let po radioterapii. Závěr: Karcinom žaludku s peritoneálními metastázami je možné léčit souběžně adaptivní radioterapií a perorálně podávaným S-1 s kurativním záměrem.

Background: There are no reports of concurrent chemoradiotherapy for gastric cancer with peritoneal oligometastases. Case description: A 70-year-old man with gastric cancer and peritoneal oligometastases received concurrent adaptive radiotherapy and oral S-1. After radiotherapy, S-1 was discontinued, and 2 years later the tumor had completely regressed, with no recurrence or metastasis 6 years after radiotherapy. Conclusion: Peritoneal oligometastatic gastric cancer may be a candidate for curative treatment with concurrent adaptive radiotherapy and oral S-1.

• MeSH
• chemoradioterapie metody   MeSH
• ftorafur aplikace a dávkování   terapeutické užití   MeSH
• kyselina oxonová aplikace a dávkování   terapeutické užití   MeSH
• lidé MeSH
• metastázy nádorů terapie   MeSH
• nádory žaludku * diagnóza   patologie   terapie   MeSH
• peritoneální nádory sekundární   terapie   MeSH
• protokoly protinádorové léčby MeSH
• senioři MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• Publikační typ
• kazuistiky MeSH

Lymphocytes, which are highly sensitive to radiation, play a crucial role in the body's defense against tumors. Radiation-induced lymphopenia has been associated with poorer outcomes in different cancer types. Despite being the largest secondary lymphoid organ, the spleen has not been officially designated as an organ at risk. This study hypothesizes a connection between spleen irradiation and lymphopenia and seeks to establish evidence-based dosage limits for the spleen. We retrospectively analyzed data from 96 patients with locally advanced gastric cancer who received postoperative chemoradiotherapy (CRT) between May 2010 and May 2017. Complete blood counts were collected before, during and after CRT. We established a model for predicting the minimum absolute lymphocyte count (Min ALC) and to investigate potential associations between spleen dosimetric variables and Min ALC. The median follow-up was 60 months. The 5-year overall survival (OS) and disease-free survival (DFS) were 65.2% and 56.8%, respectively. The median values of pre-treatment ALC, Min ALC and post-treatment ALC were 1.40 × 109, 0.23 × 109 and 0.28 × 109/L, respectively. Regression analysis confirmed that the primary tumor location, number of fractions and spleen V5 were significant predictors of Min ALC during radiation therapy. Changes in ALC (ΔALC) were identified as an independent predictor of both OS and DFS. Spleen V5 is an independent predictor for Min ALC, and the maximum dose of the spleen is associated with an increased risk of severe lymphopenia. Therefore, these doses should be restricted in clinical practice. Additionally, ΔALC can serve as a prognostic indicator for adjuvant radiotherapy in gastric cancer.

• MeSH
• celková dávka radioterapie MeSH
• chemoradioterapie MeSH
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• lymfopenie * etiologie   MeSH
• nádory žaludku * radioterapie   patologie   MeSH
• počet lymfocytů MeSH
• přežití po terapii bez příznaků nemoci MeSH
• retrospektivní studie MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• slezina * účinky záření   patologie   MeSH
• vztah dávky záření a odpovědi MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH

• MeSH
• karcinogeneze MeSH
• lidé MeSH
• metformin farmakologie   MeSH
• nádory žaludku patologie   terapie   MeSH
• resveratrol farmakologie   MeSH
• sirtuiny * metabolismus   MeSH
• Check Tag
• lidé MeSH

PURPOSE: Open-label phase II study (RELATIVITY-060) to investigate the efficacy and safety of first-line nivolumab, a PD-1-blocking antibody, plus relatlimab, a lymphocyte-activation gene 3 (LAG-3)-blocking antibody, plus chemotherapy in patients with previously untreated advanced gastric cancer (GC) or gastroesophageal junction cancer (GEJC). METHODS: Patients with unresectable, locally advanced or metastatic GC/GEJC were randomly assigned 1:1 to nivolumab + relatlimab (fixed-dose combination) + chemotherapy or nivolumab + chemotherapy. The primary end point was objective response rate (ORR; per RECIST v1.1 by blinded independent central review [BICR]) in patients whose tumors had LAG-3 expression ≥1%. RESULTS: Of 274 patients, 138 were randomly assigned to nivolumab + relatlimab + chemotherapy and 136 to nivolumab + chemotherapy. Median follow-up was 11.9 months. In patients with LAG-3 expression ≥1%, BICR-assessed ORR (95% CI) was 48% (38 to 59) in the nivolumab + relatlimab + chemotherapy arm and 61% (51 to 71) in the nivolumab + chemotherapy arm; median progression-free survival (95% CI) by BICR was 7.0 months (5.8 to 8.4) versus 8.3 months (6.9 to 12.1; hazard ratio [HR], 1.41 [95% CI, 0.97 to 2.05]), and median overall survival (95% CI) was 13.5 months (11.9 to 19.1) versus 16.0 months (10.9 to not estimable; HR, 1.04 [95% CI, 0.70 to 1.54]), respectively. Grade 3 or 4 treatment-related adverse events (TRAEs) occurred in 69% and 61% of all treated patients, and 42% and 36% of patients discontinued because of any-grade TRAEs in the nivolumab + relatlimab + chemotherapy and nivolumab + chemotherapy arms, respectively. CONCLUSION: RELATIVITY-060 did not meet its primary end point of improved ORR in patients with LAG-3 expression ≥1% when relatlimab was added to nivolumab + chemotherapy compared with nivolumab + chemotherapy. Further studies are needed to address whether adding anti-LAG-3 to anti-PD-1 plus chemotherapy can benefit specific GC/GEJC patient subgroups.

• MeSH
• adenokarcinom * farmakoterapie   patologie   mortalita   MeSH
• doba přežití bez progrese choroby MeSH
• dospělí MeSH
• gastroezofageální junkce * patologie   MeSH
• lidé středního věku MeSH
• lidé MeSH
• nádory jícnu * farmakoterapie   patologie   mortalita   MeSH
• nádory žaludku * farmakoterapie   patologie   mortalita   MeSH
• nivolumab * terapeutické užití   aplikace a dávkování   škodlivé účinky   MeSH
• protein genu 3 aktivace lymfocytů * MeSH
• protokoly antitumorózní kombinované chemoterapie * terapeutické užití   škodlivé účinky   MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• klinické zkoušky, fáze II MeSH
• multicentrická studie MeSH
• randomizované kontrolované studie MeSH

INTRODUCTION: The OligoMetastatic Esophagogastric Cancer (OMEC) project aims to provide clinical practice guidelines for the definition, diagnosis, and treatment of esophagogastric oligometastatic disease (OMD). METHODS: Guidelines were developed according to AGREE II and GRADE principles. Guidelines were based on a systematic review (OMEC-1), clinical case discussions (OMEC-2), and a Delphi consensus study (OMEC-3) by 49 European expert centers for esophagogastric cancer. OMEC identified patients for whom the term OMD is considered or could be considered. Disease-free interval (DFI) was defined as the time between primary tumor treatment and detection of OMD. RESULTS: Moderate to high quality of evidence was found (i.e. 1 randomized and 4 non-randomized phase II trials) resulting in moderate recommendations. OMD is considered in esophagogastric cancer patients with 1 organ with ≤ 3 metastases or 1 involved extra-regional lymph node station. In addition, OMD continues to be considered in patients with OMD without progression in number of metastases after systemic therapy. 18F-FDG PET/CT imaging is recommended for baseline staging and for restaging after systemic therapy when local treatment is considered. For patients with synchronous OMD or metachronous OMD and a DFI ≤ 2 years, recommended treatment consists of systemic therapy followed by restaging to assess suitability for local treatment. For patients with metachronous OMD and DFI > 2 years, upfront local treatment is additionally recommended. DISCUSSION: These multidisciplinary European clinical practice guidelines for the uniform definition, diagnosis and treatment of esophagogastric OMD can be used to standardize inclusion criteria in future clinical trials and to reduce variation in treatment.

• MeSH
• delfská metoda MeSH
• konsensus MeSH
• lidé MeSH
• metastázy nádorů MeSH
• nádory jícnu * terapie   patologie   diagnóza   MeSH
• nádory žaludku * terapie   patologie   diagnóza   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• směrnice pro lékařskou praxi MeSH
• systematický přehled MeSH
• Geografické názvy
• Evropa MeSH

Helicobacter pylori infection is a major risk factor for the development of gastric cancer. The bacteria reside in close proximity to gastric surface mucous as well as stem and progenitor cells. Here, we take advantage of wild-type and genetically engineered murine gastric organoids and organoid-derived monolayers to study the cellular targets of H. pylori-induced DNA damage and replication stress and to explore possible interactions with preexisting gastric cancer driver mutations. We find using alkaline comet assay, single-molecule DNA fiber assays, and immunofluorescence microscopy of DNA repair foci that H. pylori induces transcription-dependent DNA damage in actively replicating, Leucine-rich-repeat containing G-Protein-Coupled Receptor 5 (Lgr5)-positive antral stem and progenitor cells and their Troy-positive corpus counterparts, but not in other gastric epithelial lineages. Infection-dependent DNA damage is aggravated by Apc inactivation, but not by Trp53 or Smad4 loss, or Erbb2 overexpression. Our data suggest that H. pylori induces DNA damage in stem and progenitor cells, especially in settings of hyperproliferation due to constitutively active Wnt signaling.

• MeSH
• Helicobacter pylori * genetika   MeSH
• infekce vyvolané Helicobacter pylori * genetika   mikrobiologie   MeSH
• kmenové buňky MeSH
• lidé MeSH
• myši MeSH
• nádory žaludku * patologie   MeSH
• poškození DNA MeSH
• receptory spřažené s G-proteiny genetika   MeSH
• tumor supresorové geny MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH

Neuroendokrinní tumory představují heterogenní skupinu neoplazií vycházejících z různých anatomických lokalizací, přičemž přibližně 50 % je gastrointestinálního původu. Mezi klíčové parametry při hodnocení každého případu patří morfologie nádoru, počet mitotických buněk a index Ki-67. Smíšené adenoneuroendokrinní karcinomy (MANEC) jsou vzácné agresivní novotvary sestávající z adenokarcinomatózních i neuroendokrinních buněk, přičemž každá složka musí tvořit alespoň 30 % léze. Naším případem je 77letý polymorbidní pacient, který pro známky akutního krvácení do horní oblasti gastrointestinálního traktu s vyjádřeným anemickými syndromem podstoupil gastroskopické vyšetření s nálezem vředové léze na přední stěně žaludku na přechodu těla a antra. Při kontrolních gastroskopických vyšetřeních s odběrem biopsií byly nejdříve histologicky prokázány pouze známky chronické gastritidy při pozitivitě na Helicobacter pylori, následně nalezeny fragmenty high-grade tubulárního až tubulovilózního adenomu a struktury středně diferencovaného tubulárního adenokarcinomu. Histologickým rozborem žaludečního resekátu byl prokázán smíšený adenoneuroendokrinní karcinom s lymfangioinvazí.

Neuroendocrine tumours represent a heterogeneous group of neoplasia arising from different anatomical locations, with approximately 50% of gastrointestinal origin. Main parameters in the evaluation of each case include tumour morphology, mitotic cell count, and Ki-67 index. Mixed adeno-neuroendocrine carcinomas (MANECs) are rare aggressive neoplasms consisting of both adenocarcinomatous and neuroendocrine cells, each component constituting at least 30% of the lesion. Our case represents 77-year-old polymorbid patient who, due to signs of acute bleeding in the upper gastrointestinal tract with anaemic syndrome, underwent a gastroscopic examination for melena with the finding of an ulcer lesion on the front wall of the stomach at the junction of the body and the antrum. The control gastroscopic examinations with biopsies, at first only signs of chronic gastritis with Helicobacter pylori positivity were histologically proven, then fragments of high-grade tubular to tubulovillous adenoma and structures of moderately differentiated tubular adenocarcinoma were found. Histological analysis of the gastric resection showed mixed adeno-neuroendocrine carcinoma with lymphangioinvasion.

• MeSH
• adenokarcinom diagnóza   patologie   terapie   MeSH
• adjuvantní chemoterapie MeSH
• biopsie metody   MeSH
• diagnostické zobrazování metody   MeSH
• imunohistochemie metody   MeSH
• lidé MeSH
• nádory žaludku * diagnóza   patologie   terapie   MeSH
• neuroendokrinní karcinom diagnóza   patologie   terapie   MeSH
• senioři MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• Publikační typ
• kazuistiky MeSH