Multidisciplinary molecular tumor boards (MTB) are already well established in many comprehensive cancer centers and play an important role in the individual treatment planning for cancer patients. Comprehensive genomic profiling of tumor tissue based on next-generation sequencing is currently performed for diagnostic and mainly predictive testing. If somatic genomic variants are identified, which are suspected to be pathogenic germline variants (PGVs), MTB propose genetic counseling and germline DNA testing. Commonly used comprehensive genomic profiling approaches of tumor tissue do not include a matched germline DNA control. Therefore, the detection of PGVs could be only predicted based on the content of tumor cells (CTC) in selected tumor area (%) and variant allele frequency score (%). For conclusion, the role of a medical geneticist is essential in these cases. The overall prevalence of PGVs in patients with pancreatic ductal adenocarcinoma (PDAC) and colorectal cancer (CRC) is approximately 10%. In this single-center study, we present 37 patients with PDAC and 48 patients with CRC who were presented at MTB and tested using the large combined DNA/RNA sequencing panel. Content of tumor cells and variant allele frequency scores were evaluated in all tested patients. In case of suspicion of PGV and no previous genetic testing based on the standard guidelines, genetic counseling was recommended regardless of age, sex, and family history. In the PDAC subgroup, five patients were recommended by MTB for genetic counseling based on suspicious genetic findings. Based on a medical geneticist's decision, germline DNA sequencing was performed in four of these cases, and all of them tested positive for PGV in the following genes: ATM, ATM, BRCA1, and BRCA2. In the CRC subgroup, no PGV was confirmed in the two patients genetically tested based on the MTB recommendations. Furthermore, we present data from our center's registry of patients with PDAC and CRC who underwent genetic counseling and germline DNA testing based on the standard screening criteria. Our data confirm that comprehensive genomic profiling of tumor tissue can identify patients with hereditary forms of PDAC, who could remain unidentified by standard screening for hereditary forms of cancer.

• Klíčová slova
• colorectal cancer, germline variants, next-generation sequencing, pancreatic cancer, somatic variants,
• MeSH
• dospělí MeSH
• duktální karcinom slinivky břišní * genetika   MeSH
• frekvence genu MeSH
• genetické poradenství MeSH
• genetické testování MeSH
• genomika metody   MeSH
• kolorektální nádory * genetika   patologie   MeSH
• lidé středního věku MeSH
• lidé MeSH
• nádory slinivky břišní * genetika   patologie   MeSH
• náhodný nález * MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• vysoce účinné nukleotidové sekvenování MeSH
• zárodečné mutace * 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

BACKGROUND: Pancreaticoduodenectomy is associated with an incidence of postoperative complications of approximately 41%. One of the most severe complications is a postoperative pancreatic fistula. The exact cause of postoperative fistula development is still unknown, but it appears to be multifactorial. Proper perfusion of pancreatic remnant is essential for the healing of pancreaticojejunostomy. To date, there is no method to reliably evaluate the vascular supply of the remnant. One of the methods for the assessment of organ perfusion is the indocyanine green fluorescence. This study aims to determine if indocyanine green fluorescence is a reliable method to measure the perfusion of the post-resection pancreatic remnant. The secondary outcome is to determine if intraoperative evaluation of the vascular supply of the post-resection remnant may predict the increased risk of postoperative pancreatic fistula development. METHODS: This study is designed as a prospective, observational study. All consecutive patients undergoing open or robotic pancreaticoduodenectomies at our department during the 1st May 2024-31st December 2026 period will be enrolled. The exclusion criteria are an allergy to indocyanine green and refusal by the patient. The adequacy of the vascular supply of the post-resection pancreatic remnant will be intraoperatively evaluated using a fluorescence detector. Patients will be divided into two groups: Those with high risk of pancreatic fistula development and those with low risk. The incidence of pancreatic fistulas in both groups is to be compared. Postoperative data including morbidity, mortality, hospital stay, intensive care unit stay and postoperative fistula development will be collected. DISCUSSION: If an intraoperative assessment of the perfusion of post-resection pancreatic remnant using indocyanine green is proven to be a suitable method to estimate the increased risk of the pancreatic fistula, the list of the existing known risk factors could be expanded. In the most high-risk patients the modification of the surgical procedure could be considered. TRIAL REGISTRATION: Number: NCT06198400 ClinicalTrials.Gov. Date 08.01.2024.

• Klíčová slova
• ICG, Minimal invasive surgery, Pancreatic cancer, Pancreatic perfusion, Pancreatic surgery, Prospective study,
• MeSH
• fluorescence MeSH
• indokyanová zeleň * MeSH
• lidé MeSH
• pankreas krevní zásobení   chirurgie   MeSH
• pankreatická píštěl * etiologie   epidemiologie   MeSH
• pankreatoduodenektomie * škodlivé účinky   metody   MeSH
• pooperační komplikace * etiologie   diagnóza   MeSH
• pozorovací studie jako téma MeSH
• prospektivní studie MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• protokol klinické studie MeSH
• Názvy látek
• indokyanová zeleň * MeSH

Photodynamic therapy (PDT) has the potential to cure pancreatic cancer with minimal side effects. Visible wavelengths are primarily used to activate hydrophobic photosensitizers, but in clinical practice, these wavelengths do not sufficiently penetrate deeper localized tumor cells. In this work, NaYF4:Yb3+,Er3+,Fe2+ upconversion nanoparticles (UCNPs) were coated with polymer and labeled with meta-tetra(hydroxyphenyl)chlorin (mTHPC; temoporfin) to enable near-infrared light (NIR)-triggered PDT of pancreatic cancer. The coating consisted of alendronate-terminated poly[N,N-dimethylacrylamide-co-2-aminoethylacrylamide]-graft-poly(ethylene glycol) [P(DMA-AEM)-PEG-Ale] to ensure the chemical and colloidal stability of the particles in aqueous physiological fluids, thereby also improving the therapeutic efficacy. The designed particles were well tolerated by the human pancreatic adenocarcinoma cell lines CAPAN-2, PANC-1, and PA-TU-8902. After intratumoral injection of mTHPC-conjugated polymer-coated UCNPs and subsequent exposure to 980 nm NIR light, excellent PDT efficacy was achieved in tumor-bearing mice.

• MeSH
• akrylamidy chemie   MeSH
• fotochemoterapie * metody   MeSH
• fotosenzibilizující látky * chemie   farmakologie   MeSH
• infračervené záření MeSH
• koloidy chemie   MeSH
• lidé MeSH
• mesoporfyriny * chemie   farmakologie   MeSH
• myši inbrední BALB C MeSH
• myši nahé MeSH
• myši MeSH
• nádorové buněčné linie MeSH
• nádory slinivky břišní * farmakoterapie   patologie   MeSH
• nanočástice chemie   MeSH
• polyethylenglykoly * chemie   MeSH
• polymery chemie   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• akrylamidy MeSH
• fotosenzibilizující látky * MeSH
• koloidy MeSH
• mesoporfyriny * MeSH
• polyethylenglykoly * MeSH
• polymery MeSH
• temoporfin MeSH Prohlížeč

Gastrointestinal cancers continue to pose a significant global health challenge, with millions of new cases diagnosed each year. Despite advancements in treatment, the prognosis for many patients remains poor. This article explores the potential of garcinol, a polyisoprenylated benzophenone found in various Garcinia species, as a therapeutic agent against gastrointestinal malignancies. The objective is to review recent research on garcinol's anticancer properties, its mechanisms of action, and safety aspects. Garcinol exhibits anticancer effects in esophageal, gastric, colorectal, pancreatic, and liver cancers by inhibiting metastasis, inducing apoptosis, and targeting key molecular pathways in cancer progression. Nanotechnology is explored as a means to enhance garcinol delivery and efficacy. Safety assessments suggest a promising toxicity profile. Garcinol shows significant potential as a natural therapeutic agent for gastrointestinal cancers, and future research is needed on optimizing its delivery, exploring synergistic combinations, and conducting clinical trials to validate its efficacy and safety for clinical applications.

• Klíčová slova
• Apoptosis, Garcinol, Gastrointestinal cancers, Pharmacokinetics, Targeted therapy,
• MeSH
• fytogenní protinádorové látky terapeutické užití   farmakologie   MeSH
• gastrointestinální nádory * prevence a kontrola   farmakoterapie   MeSH
• lidé MeSH
• terpeny * terapeutické užití   farmakologie   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH
• Názvy látek
• fytogenní protinádorové látky MeSH
• garcinol MeSH Prohlížeč
• terpeny * MeSH

BACKGROUND: Pancreatic ductal adenocarcinoma remains one of the most lethal malignancies, with few treatment options. NAPOLI 3 aimed to compare the efficacy and safety of NALIRIFOX versus nab-paclitaxel and gemcitabine as first-line therapy for metastatic pancreatic ductal adenocarcinoma (mPDAC). METHODS: NAPOLI 3 was a randomised, open-label, phase 3 study conducted at 187 community and academic sites in 18 countries worldwide across Europe, North America, South America, Asia, and Australia. Patients with mPDAC and Eastern Cooperative Oncology Group performance status score 0 or 1 were randomly assigned (1:1) to receive NALIRIFOX (liposomal irinotecan 50 mg/m2, oxaliplatin 60 mg/m2, leucovorin 400 mg/m2, and fluorouracil 2400 mg/m2, administered sequentially as a continuous intravenous infusion over 46 h) on days 1 and 15 of a 28-day cycle or nab-paclitaxel 125 mg/m2 and gemcitabine 1000 mg/m2, administered intravenously, on days 1, 8, and 15 of a 28-day cycle. Balanced block randomisation was stratified by geographical region, performance status, and liver metastases, managed through an interactive web response system. The primary endpoint was overall survival in the intention-to-treat population, evaluated when at least 543 events were observed across the two treatment groups. Safety was evaluated in all patients who received at least one dose of study treatment. This completed trial is registered with ClinicalTrials.gov, NCT04083235. FINDINGS: Between Feb 19, 2020 and Aug 17, 2021, 770 patients were randomly assigned (NALIRIFOX, 383; nab-paclitaxel-gemcitabine, 387; median follow-up 16·1 months [IQR 13·4-19·1]). Median overall survival was 11·1 months (95% CI 10·0-12·1) with NALIRIFOX versus 9·2 months (8·3-10·6) with nab-paclitaxel-gemcitabine (hazard ratio 0·83; 95% CI 0·70-0·99; p=0·036). Grade 3 or higher treatment-emergent adverse events occurred in 322 (87%) of 370 patients receiving NALIRIFOX and 326 (86%) of 379 patients receiving nab-paclitaxel-gemcitabine; treatment-related deaths occurred in six (2%) patients in the NALIRIFOX group and eight (2%) patients in the nab-paclitaxel-gemcitabine group. INTERPRETATION: Our findings support use of the NALIRIFOX regimen as a possible reference regimen for first-line treatment of mPDAC. FUNDING: Ipsen. TRANSLATION: For the plain language summary see Supplementary Materials section.

• MeSH
• adenokarcinom * farmakoterapie   MeSH
• albuminy MeSH
• gemcitabin MeSH
• lidé MeSH
• nádory slinivky břišní * farmakoterapie   patologie   MeSH
• paclitaxel MeSH
• protokoly protinádorové kombinované chemoterapie škodlivé účinky   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• klinické zkoušky, fáze III MeSH
• randomizované kontrolované studie MeSH
• Názvy látek
• 130-nm albumin-bound paclitaxel MeSH Prohlížeč
• albuminy MeSH
• gemcitabin MeSH
• paclitaxel MeSH

Despite development in cancer treatment and prevention options during the past few years, cancer of the pancreas remains a diagnosis associated with poor prognosis and limited options for prevention. Diet has proven to be an important risk factor for development of many types of cancer, particularly for cancers of the digestive system. Still, evidence regarding its relation to pancreatic cancer remains ambiguous. To investigate the relationship between diet and pancreatic cancer, an analysis of dietary patterns in participants from the Norwegian Women and Cancer Study (n = 89,156; 305 pancreatic cancer cases) was performed. Cox regression analysis was used for studying possible associations between dietary patterns, derived from principal component analysis, and pancreatic cancer incidence. The four most prominent dietary patterns were identified and described: European pattern, animal food consumers' dietary pattern, traditional Norwegian pattern, and alcohol-abstaining dietary pattern. In analysis without adjustment for confounders, being in the highest tertile of the abstaining dietary pattern was associated with lower risk of pancreatic cancer in comparison to the lowest tertile (hazard ratios [HR]: 0.66, 95% confidence interval [CI]: 0.49-0.89). After additional adjustment for height and smoking status, no dietary pattern was associated with increased pancreatic cancer risk, nor was there any difference in effect estimates between strata of smokers and non-smokers. The results of our current analysis do not support the role of major dietary patterns in the development of pancreatic cancer.

• Klíčová slova
• Norway, Pancreatic cancer, dietary patterns, prospective cohort, women,
• Publikační typ
• časopisecké články MeSH

Pancreatic cancer (PDAC) has a poor prognosis despite surgical removal and adjuvant therapy. Additionally, the effects of postoperative analgesia with morphine and piritramide on survival among PDAC patients are unknown, as are their interactions with opioid/cannabinoid receptor gene expressions in PDAC tissue. Cancer-specific survival data for 71 PDAC patients who underwent radical surgery followed by postoperative analgesia with morphine (n = 48) or piritramide (n = 23) were therefore analyzed in conjunction with opioid/cannabinoid receptor gene expressions in the patients' tumors. Receptor gene expressions were determined using the quantitative real-time polymerase chain reaction. Patients receiving morphine had significantly longer cancer-specific survival (CSS) than those receiving piritramide postoperative analgesia (median 22.4 vs. 15 months; p = 0.038). This finding was supported by multivariate modelling (p < 0.001). The morphine and piritramide groups had similar morphine equipotent doses, receptor expression, and baseline characteristics. The opioid/cannabinoid receptor gene expression was analyzed in a group of 130 pancreatic cancer patients. Of the studied receptors, high cannabinoid receptor 2 (CB2) and opioid growth factor receptor (OGFR) gene expressions have a positive influence on the length of overall survival (OS; p = 0.029, resp. p = 0.01). Conversely, high delta opioid receptor gene expression shortened OS (p = 0.043). Multivariate modelling indicated that high CB2 and OGFR expression improved OS (HR = 0.538, p = 0.011, resp. HR = 0.435, p = 0.001), while high OPRD receptor expression shortened OS (HR = 2.264, p = 0.002). Morphine analgesia, CB2, and OGFR cancer tissue gene expression thus improved CSS resp. OS after radical PDAC surgery, whereas delta opioid receptor expression shortened OS.

• Klíčová slova
• cancer recurrence, cannabinoid receptors, morphine, opioid receptors, pancreatic cancer, pancreatic surgery, patient survival, piritramide, postoperative analgesia,
• Publikační typ
• časopisecké články MeSH

BACKGROUND AND OBJECTIVE: Obesity is a major lifestyle risk factor that contributes greatly to the burden of disease, including cancer. Overweight and obesity have shown association with several types of cancer. As Czechia is one of the most overweight countries in Europe, and has high cancer mortality, this study aims to investigate the country's long-term burden of obesity-related cancer. METHODS: Using the Czech National Cancer Register and the NCD Risk Factor Collaboration (NCD-RisC), standardized incidence and mortality rates were calculated for 12 types of cancer related to obesity for the years 1985-2018. Population attributable fractions (PAF) were calculated. Finally, the standardized attributable rates were calculated from the standardized incidence and mortality rates and the PAFs. RESULTS: Approximately 11.0% of selected cancer cases in the male population and 12.3% in the female population were attributable to overweight and obesity in 2018. Since the beginning of the millennium, obesity attributable cancer mortality has dropped, while incidence has remained constant. The incidence throughout the whole period was almost twice as high (18.7 cases per 100,000 population in 2018) in women than in men (10.9 cases per 100,000 population in 2018). CONCLUSION: Obesity-related cancer mortality in Czechia has declined in the last two decades, but the incidence has remained constant. Given the increasing prevalence of overweight and obesity in western countries, this issue needs to be prioritized in future healthcare and policy making.

• Klíčová slova
• Cancer, Czech Republic, Disease burden, Overweight, Population attributable fraction,
• MeSH
• lidé MeSH
• nádory * epidemiologie   MeSH
• nadváha epidemiologie   MeSH
• neinfekční nemoci * MeSH
• obezita epidemiologie   MeSH
• rizikové faktory MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• Geografické názvy
• Česká republika epidemiologie   MeSH

The advancement in molecular techniques has been attributed to the quality and significance of cancer research. Pancreatic cancer (PC) is one of the rare cancers with aggressive behavior and a high mortality rate. The asymptomatic nature of the disease until its advanced stage has resulted in late diagnosis as well as poor prognosis. The heterogeneous character of PC has complicated cancer development and progression studies. The analysis of bulk tissues of the disease was insufficient to understand the disease, hence, the introduction of the single-cell separating technique aided researchers to decipher more about the specific cell population of tumors. This review gives an overview of the Laser Capture Microdissection (LCM) technique, one of the single-cell separation methods used in PC research.

• Klíčová slova
• Laser Capture Microdissection (LCM), hypoxia, intraductal papillary mucinous neoplasm (IPMN), metastasis, pancreatic cancer, single-cell separation,
• MeSH
• duktální karcinom slinivky břišní * patologie   MeSH
• laserová záchytná mikrodisekce MeSH
• lidé MeSH
• nádory slinivky břišní * patologie   MeSH
• pankreas patologie   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH

An 11-year-old intact female Pomeranian dog was referred for jaundice, anorexia, and vomiting. The blood analysis revealed increased alanine aminotransferase, alkaline phosphatase, and gamma-glutamyl transpeptidase. The serum canine pancreatic lipase immunoreactivity was within the normal reference range. The radiography revealed no significant findings. On ultrasound, the gallbladder was enlarged with a markedly distended common bile duct (CBD) measuring up to 6 mm in diameter. The pancreas had an irregular contour, a hypoechoic peripheral rim, multiple hyperechoic foci with acoustic shadowing, and showed increased echogenicity of the adjacent mesentery. Based on these results, an extrahepatic biliary obstruction secondary to the presumed chronic pancreatitis was diagnosed. The computed tomography (CT) images showed a hypoattenuating pancreatic parenchyma compared to the liver in the early phase, as well as multiple calcifications. A laparotomy was performed to reserve the patency of the CBD. The histopathological examination of the pancreas revealed exocrine pancreatic adenocarcinoma. While various appearances of exocrine pancreatic adenocarcinoma on CT have been reported in humans, CT features of pancreatic adenocarcinoma have not been well-established in dogs. The purpose of this report is to describe the atypical imaging features of pancreatic adenocarcinoma that are similar to those of chronic pancreatitis in a dog.

• Klíčová slova
• computed tomography, exocrine pancreatic adenocarcinoma, pancreatitis, ultrasound,
• Publikační typ
• časopisecké články MeSH
• kazuistiky MeSH