INTRODUCTION: During pregnancy, acute appendicitis is responsible for about two-thirds of nontraumatic surgical emergencies. The aim of this study was to investigate whether the group of pregnant patients differs from the group of the normal population in perioperative features and whether surgery during pregnancy affects its further course. METHODS: We retrospectively analyzed a cohort of 1,054 patients who underwent surgery for signs of acute appendicitis. The cohort included 16 pregnant patients (1.5%), 6 patients (37.5%) in the first trimester, 10 patients (62.5%) in the second. Perioperative features of the groups were compared, and postoperative course of pregnancy was followed. RESULTS: We discovered that pregnant patients had a higher ratio of negative appendectomies (25% vs. 5.3%, p = 0.010) and shorter operating time (40 min vs. 51 min, p = 0.013). CONCLUSION: Based on our data, acute appendectomy in pregnancy is associated with a higher rate of negative appendectomy and shorter operating time. Due to the small number of pregnant patients in the group and the occurrence of only one first trimester miscarriage of unknown etiology, it is not possible to clearly draw conclusion about the impact of acute appendectomy on the further course of pregnancy and further investigation is needed.

• Klíčová slova
• Abdominal surgery, Acute appendicitis, Appendectomy, Pregnancy, Visceral surgery,
• Publikační typ
• časopisecké články MeSH

INTRODUCTION: Appendectomy for acute appendicitis is the most common surgical procedure performed during pregnancy. The primary treatment for acute appendicitis is emergency surgery, which can be particularly challenging due to altered anatomical conditions. Preoperative and postoperative care may require certain examinations due to pregnancy that are not standard within surgical practice or may be overlooked by the attending gynecologist. CASE PRESENTATION: A patient at 31 weeks of gestation presented to the obstetric clinic with an acute onset of acute appendicitis. After completing all necessary examinations and a thorough multidisciplinary evaluation, a successful laparoscopic appendectomy was performed. The subsequent hospitalization was complicated by the onset of uterine contractions, for which tocolysis was administered in combination with corticosteroid therapy to induce fetal lung maturity. CONCLUSION: In the presented case report, we demonstrate an example of the appropriate multidisciplinary approach with an analysis of the specific steps that should be taken to maximize the benefit for both the fetus and the mother, as well as the surgical team. In the discussion, we outline the steps that should be followed for patient benefit and forensic reasons.

• Klíčová slova
• Appendicitis, Laparoscopic surgery, Management, Minimally invasive surgery, Obstetrics, Pregnancy, Surgery,
• Publikační typ
• časopisecké články MeSH
• kazuistiky MeSH

Pleiotropic variants (i.e. genetic polymorphisms influencing more than one phenotype) are often associated with cancer risk. A scan of pleiotropic variants was successfully conducted 10 years ago in relation to pancreatic ductal adenocarcinoma susceptibility. However, in the last decade, genetic association studies performed on several human traits have greatly increased the number of known pleiotropic variants. Based on the hypothesis that variants already associated with a least one trait have a higher probability of association with other traits, 61 052 variants reported to be associated by at least one genome-wide association study with at least one human trait were tested in the present study consisting of two phases (discovery and validation), comprising a total of 16 055 pancreatic ductal adenocarcinoma (PDAC) cases and 212 149 controls. The meta-analysis of the two phases showed two loci (10q21.1-rs4948550 (P = 6.52 × 10-5) and 7q36.3-rs288762 (P = 3.03 × 10-5) potentially associated with PDAC risk. 10q21.1-rs4948550 shows a high degree of pleiotropy and it is also associated with colorectal cancer risk while 7q36.3-rs288762 is situated 28,558 base pairs upstream of the Sonic Hedgehog (SHH) gene, which is involved in the cell-differentiation process and PDAC etiopathogenesis. In conclusion, none of the single nucleotide polymorphisms (SNPs) showed a formally statistically significant association after correction for multiple testing. However, given their pleiotropic nature and association with various human traits including colorectal cancer, the two SNPs showing the best associations with PDAC risk merit further investigation through fine mapping and ad hoc functional studies.

• Klíčová slova
• genetic susceptibility, pancreatic cancer, pleiotropy, single nucleotide polymorphism,
• MeSH
• celogenomová asociační studie MeSH
• duktální karcinom slinivky břišní * genetika   MeSH
• genetická pleiotropie * MeSH
• genetická predispozice k nemoci * MeSH
• jednonukleotidový polymorfismus MeSH
• lidé MeSH
• nádory slinivky břišní * genetika   MeSH
• studie případů a kontrol MeSH
• Check Tag
• lidé MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• metaanalýza MeSH

BACKGROUND AND OBJECTIVE: Undifferentiated carcinoma of the pancreas with osteoclast-like giant cells (UCOGC) is a rare variant of malignant pancreatic tumor. There is still no standardized treatment for this uncommon subtype, as surgical resection with lymphadenectomy is the only potentially curative treatment so far. In this paper, we describe the current knowledge of this very rare specific subtype of pancreatic cancer (PC) as a narrative review. METHODS: For this review, we did not specify the time range of studies referred to due to limited data availability. Our inclusion criteria comprised previous studies, which specifically focused on the rare UCOGC subtype of PC as a confirmed histopathology, either pure or present together with other subtypes. We disregarded the studies involving any other PC subtype but not UCOGC, including undifferentiated and anaplastic carcinomas without osteoclast-like giant cell components. KEY CONTENT AND FINDINGS: The limited available data precludes a definitive assessment of the efficacy of both neoadjuvant and adjuvant chemotherapy in the treatment of UCOGC. Monoclonal antibody pembrolizumab has been proven to be effective in metastatic cases. Multiple cases demonstrate a better overall survival rate for patients with UCOGC only versus those having UCOGC as a component with a pancreatic ductal adenocarcinoma (PDAC) histopathological subtype. The same conclusion can be also drawn comparing the survival rate of patients having pure UCOGC versus UCOGC with associated PDAC. Programmed cell death ligand-1 expression has been shown to be an important determinant, which shortens the survival period of patients diagnosed with UCOGC. CONCLUSIONS: The rarity of UCOGC limits data for clinical courses and treatment plans. We need more data to better understand the relationship between pathogenic mutations, histological subtypes, and prognosis in PC, including UCOGC. Understanding UCOGC's molecular, clinical, radiological, and pathological characteristics can lead to earlier, more accurate diagnoses and better management.

• Klíčová slova
• Pancreatic neoplasms, carcinoma, undifferentiated, review, therapeutics,
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH

Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal cancers with patients having unresectable or metastatic disease at diagnosis, with poor prognosis and very short survival. Given that genetic variation within autophagy-related genes influences autophagic flux and susceptibility to solid cancers, we decided to investigate whether 55,583 single nucleotide polymorphisms (SNPs) within 234 autophagy-related genes could influence the risk of developing PDAC in three large independent cohorts of European ancestry including 12,754 PDAC cases and 324,926 controls. The meta-analysis of these populations identified, for the first time, the association of the BIDrs9604789 variant with an increased risk of developing the disease (ORMeta = 1.31, p = 9.67 × 10-6). We also confirmed the association of TP63rs1515496 and TP63rs35389543 variants with PDAC risk (OR = 0.89, p = 6.27 × 10-8 and OR = 1.16, p = 2.74 × 10-5). Although it is known that BID induces autophagy and TP63 promotes cell growth, cell motility and invasion, we also found that carriers of the TP63rs1515496G allele had increased numbers of FOXP3+ Helios+ T regulatory cells and CD45RA+ T regulatory cells (p = 7.67 × 10-4 and p = 1.56 × 10-3), but also decreased levels of CD4+ T regulatory cells (p = 7.86 × 10-4). These results were in agreement with research suggesting that the TP63rs1515496 variant alters binding sites for FOXA1 and CTCF, which are transcription factors involved in modulating specific subsets of regulatory T cells. In conclusion, this study identifies BID as new susceptibility locus for PDAC and confirms previous studies suggesting that the TP63 gene is involved in the development of PDAC. This study also suggests new pathogenic mechanisms of the TP63 locus in PDAC.

• Klíčová slova
• autophagy, functional characterization, genetic variants, pancreatic cancer, polymorphisms, susceptibility,
• MeSH
• autofagie * genetika   MeSH
• běloši genetika   MeSH
• duktální karcinom slinivky břišní * genetika   patologie   MeSH
• forkhead transkripční faktory MeSH
• genetická predispozice k nemoci * MeSH
• hepatocytární jaderný faktor 3-alfa genetika   metabolismus   MeSH
• jednonukleotidový polymorfismus * MeSH
• kohortové studie MeSH
• lidé MeSH
• nádorové biomarkery * genetika   MeSH
• nádorové supresorové proteiny * genetika   MeSH
• nádory slinivky břišní * genetika   patologie   MeSH
• studie případů a kontrol MeSH
• transkripční faktory genetika   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• metaanalýza MeSH
• Názvy látek
• forkhead transkripční faktory MeSH
• FOXA1 protein, human MeSH Prohlížeč
• FOXP3 protein, human MeSH Prohlížeč
• hepatocytární jaderný faktor 3-alfa MeSH
• nádorové biomarkery * MeSH
• nádorové supresorové proteiny * MeSH
• TP63 protein, human MeSH Prohlížeč
• transkripční faktory MeSH

Patient-derived organoids (PDOs) and xenografts (PDXs) are powerful tools for personalized medicine in pancreatic cancer (PC) research. This study explores the complementary strengths of PDOs and PDXs in terms of practicality, genetic fidelity, cost, and labor considerations. Among other models like 2D cell cultures, spheroids, cancer-on-chip systems, cell line-derived xenografts (CDX), and genetically engineered mouse models (GEMMs), PDOs and PDXs uniquely balance genetic fidelity and personalized medicine potential, offering distinct advantages over the simplicity of 2D cultures and the advanced, but often resource-intensive, GEMMs and cancer-on-chip systems. PDOs excel in high-throughput drug screening due to their ease of use, lower cost, and shorter experimental timelines. However, they lack a complete tumor microenvironment. Conversely, PDXs offer a more complex microenvironment that closely reflects patient tumors, potentially leading to more clinically relevant results. Despite limitations in size, number of specimens, and engraftment success, PDXs demonstrate significant concordance with patient responses to treatment, highlighting their value in personalized medicine. Both models exhibit significant genetic fidelity, making them suitable for drug sensitivity testing. The choice between PDOs and PDXs depends on the research focus, resource availability, and desired level of microenvironment complexity. PDOs are advantageous for high-throughput screening of a diverse array of potential therapeutic agents due to their relative ease of culture and scalability. PDXs, on the other hand, offer a more physiologically relevant model, allowing for a comprehensive evaluation of drug efficacy and mechanisms of action.

• Klíčová slova
• Adjuvant, Animal, Chemotherapy, Heterografts, Models, Organoids, Pancreatic neoplasms,
• MeSH
• individualizovaná medicína * metody   MeSH
• lidé MeSH
• myši MeSH
• nádorové mikroprostředí účinky léků   MeSH
• nádory slinivky břišní * farmakoterapie   patologie   genetika   MeSH
• organoidy * účinky léků   patologie   MeSH
• protinádorové látky farmakologie   terapeutické užití   MeSH
• screeningové testy protinádorových léčiv metody   MeSH
• xenogenní modely - testy protinádorové aktivity * metody   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH
• Názvy látek
• protinádorové látky MeSH

BACKGROUND/AIM: Inflammation-based prognostic scores have shown prognostic significance and have been associated with clinical outcomes in various types of cancer. Inflammation is known to promote tumor progression leading to reduced survival. In pancreatic cancer, systemic inflammation is common and contributes to its dismal prognosis. Although the prognosis of pancreatic cancer is improving with the introduction of new drugs, the prognostic indicators are still poorly understood. The present study aimed to evaluate inflammation-based prognostic scores in patients with metastatic pancreatic cancer receiving first-line chemotherapy. PATIENTS AND METHODS: A total of 43 patients with metastatic pancreatic cancer undergoing first-line chemotherapy (gemcitabine+nab-paclitaxel and mFOLFIRINOX) in our institution were analyzed. Baseline clinicopathological and pre-treatment laboratory data were collected. Survival was estimated using the Kaplan-Meier method and survival differences were evaluated using the log-rank test. RESULTS: In the whole cohort, we identified lymphocyte-to-monocyte ratio ≥3, systemic inflammatory response index <2.3, carcinoembryonic antigen <2.5, neutrophil-to-lymphocyte ratio <5, Memorial Sloane Kettering score <2, and prognostic index <2 as prognostic markers associated with improved overall survival in patients receiving first-line chemotherapy. CONCLUSION: The current analysis showed an association between inflammatory-based prognostic markers and overall survival in patients with metastatic pancreatic cancer treated in a real-world setting at a single institution.

• Klíčová slova
• Metastatic pancreatic cancer, inflammation-based prognostic markers, overall survival, palliative chemotherapy, real-world data,
• MeSH
• albuminy aplikace a dávkování   MeSH
• deoxycytidin analogy a deriváty   aplikace a dávkování   terapeutické užití   MeSH
• dospělí MeSH
• fluoruracil aplikace a dávkování   terapeutické užití   MeSH
• gemcitabin MeSH
• irinotekan aplikace a dávkování   terapeutické užití   MeSH
• Kaplanův-Meierův odhad MeSH
• leukovorin aplikace a dávkování   terapeutické užití   MeSH
• lidé středního věku MeSH
• lidé MeSH
• nádory slinivky břišní * farmakoterapie   mortalita   patologie   MeSH
• neutrofily patologie   MeSH
• oxaliplatin aplikace a dávkování   terapeutické užití   MeSH
• paclitaxel aplikace a dávkování   MeSH
• paliativní péče * metody   MeSH
• prognóza MeSH
• protokoly protinádorové kombinované chemoterapie * terapeutické užití   MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• zánět * patologie   farmakoterapie   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
• Názvy látek
• 130-nm albumin-bound paclitaxel MeSH Prohlížeč
• albuminy MeSH
• deoxycytidin MeSH
• fluoruracil MeSH
• folfirinox MeSH Prohlížeč
• gemcitabin MeSH
• irinotekan MeSH
• leukovorin MeSH
• oxaliplatin MeSH
• paclitaxel MeSH

Correlated regions of systemic interindividual variation (CoRSIV) represent a small proportion of the human genome showing DNA methylation patterns that are the same in all human tissues, are different among individuals, and are partially regulated by genetic variants in cis. In this study we aimed at investigating single-nucleotide polymorphisms (SNPs) within CoRSIVs and their involvement with pancreatic ductal adenocarcinoma (PDAC) risk. We analyzed 29,099 CoRSIV-SNPs and 133,615 CoRSIV-mQTLs in 14,394 cases and 247,022 controls of European and Asian descent. We observed that the A allele of the rs2976395 SNP was associated with increased PDAC risk in Europeans (p = 2.81 × 10-5). This SNP lies in the prostate stem cell antigen gene and is in perfect linkage disequilibrium with a variant (rs2294008) that has been reported to be associated with risk of many other cancer types. The A allele is associated with the DNA methylation level of the gene according to the PanCan-meQTL database and with overexpression according to QTLbase. The expression of the gene has been observed to be deregulated in many tumors of the gastrointestinal tract including pancreatic cancer; however, functional studies are needed to elucidate the function relevance of the association.

• Klíčová slova
• DNA methylation, pancreatic cancer, risk factors, single‐nucleotide polymorphism,
• MeSH
• alely MeSH
• antigeny nádorové * genetika   MeSH
• Asijci genetika   MeSH
• běloši genetika   MeSH
• duktální karcinom slinivky břišní * genetika   MeSH
• genetická predispozice k nemoci MeSH
• GPI-vázané proteiny * genetika   MeSH
• jednonukleotidový polymorfismus MeSH
• lidé středního věku MeSH
• lidé MeSH
• lokus kvantitativního znaku MeSH
• metylace DNA MeSH
• nádorové proteiny * genetika   MeSH
• nádory slinivky břišní * genetika   MeSH
• studie případů a kontrol MeSH
• vazebná nerovnováha * MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• antigeny nádorové * MeSH
• GPI-vázané proteiny * MeSH
• nádorové proteiny * MeSH
• PSCA protein, human MeSH Prohlížeč

Undifferentiated carcinoma with osteoclast-like giant cells (UCOGC) of the pancreas represents a rare subtype of pancreatic ductal adenocarcinoma (PDAC). Despite a distinct morphology and specific clinical behavior, UCOGCs exhibit unexpected similarities in regard to DNA mutational profiles with conventional PDAC. Treating pancreatic ductal adenocarcinoma is particularly challenging, with limited prospects for cure. As with many other malignant neoplasms, the exploration of microRNAs (miRNAs, miRs) in regulating the biological characteristics of pancreatic cancer is undergoing extensive investigation to enhance tumor diagnostics and unveil the therapeutic possibilities. Herein, we evaluated the expression of miR-21, -96, -148a, -155, -196a, -210, and -217 in UCOGCs and poorly differentiated (grade 3, G3) PDACs. The expression of miR-21, miR-155, and miR-210 in both UCOGCs and G3 PDACs was significantly upregulated compared to the levels in normal tissue, while the levels of miR-148a and miR-217 were downregulated. We did not find any significant differences between cancerous and normal tissues for the expression of miR-96 and miR-196a in G3 PDACs, whereas miR-196a was slightly, but significantly, downregulated in UCOGCs. On the other hand, we have not observed significant differences in the expression of the majority of miRNAs between UCOGC and G3 PDAC, with the exception of miR-155. UCOGC samples demonstrated lower mean levels of miR-155 in comparison with those in G3 PDACs.

• Klíčová slova
• ductal adenocarcinoma, miRNA, pancreas, undifferentiated carcinoma with osteoclast-like giant cells,
• Publikační typ
• časopisecké články MeSH

Pancreatic cancer is a severe malignancy with increasing incidence and high mortality due to late diagnosis and low sensitivity to treatments. Search for the most appropriate drugs and therapeutic regimens is the most promising way to improve the treatment outcomes of the patients. This study aimed to compare (1) in vitro efficacy and (2) in vivo antitumor effects of conventional paclitaxel and the newly synthesized second (SB-T-1216) and third (SB-T-121605 and SB-T-121606) generation taxanes in KRAS wild type BxPC-3 and more aggressive KRAS G12V mutated Paca-44 pancreatic cancer cell line models. In vitro, paclitaxel efficacy was 27.6 ± 1.7 nM, while SB-Ts showed 1.7-7.4 times higher efficacy. Incorporation of SB-T-121605 and SB-T-121606 into in vivo therapeutic regimens containing paclitaxel was effective in suppressing tumor growth in Paca-44 tumor-bearing mice at small doses (≤3 mg/kg). SB-T-121605 and SB-T-121606 in combination with paclitaxel are promising candidates for the next phase of preclinical testing.

• Klíčová slova
• Cancer, Cell biology, Pharmacology,
• Publikační typ
• časopisecké články MeSH