OBJECTIVES: Despite increasing interest, prospective data on the use of degradable starch microsphere-transarterial chemoembolization (DSM-TACE) in the management of patients with unresectable HCC are still scarce. The objective of the HepaStar study was to collect prospective safety and effectiveness data in a prospective multicenter observational study. MATERIALS AND METHODS: Between January 2017 and December 2022, consecutive participants with unresectable or recurrent HCC treated with DSM-TACE as standard of care at 6 participating centers in Europe were enrolled. Tumor response was evaluated according to the mRECIST criteria. Overall survival (OS), progression-free survival (PFS), and adverse events (AEs) were assessed by using Kaplan-Meier analysis and Common Terminology Criteria for Adverse Events, version 5. Liver function deterioration was assessed by monitoring changes in liver blood tests during the follow-up. RESULTS: Seventy-nine participants (median age, 69 years (IQR, 51-87 years); 67 men (85%)) were enrolled and treated. The median follow-up time was 18 months (IQR 9.5-38.0 months). The estimated median OS and PFS for the entire cohort was 32 months (CI, 95% 21-NaN) and 9 months (CI, 95% 7-NaN), respectively. Eleven (13.9%) participants experienced at least one grade 3 or 4 AE. The most frequent grade 3-4 AE was elevated bilirubin (2.2%, 5 of 79). Deterioration of bilirubin, AST, ALT, and albumin were observed in 24.1%, 23.7%, 19%, and 24% of participants, respectively. CONCLUSION: DSM-TACE achieves promising survival in patients with unresectable or recurrent HCC. This technique shows a favorable safety profile both in terms of treatment-related AEs and liver function deterioration. KEY POINTS: Question Although degradable starch microspheres transarterial chemoembolization is widely used in clinical practice across Europe, prospective data on its application in hepatocellular carcinoma patients remains limited. Findings Degradable starch microspheres transarterial chemoembolization results in promising survival rates, good tumor response rates, and low rates of treatment-related adverse events. Clinical relevance In patients with unresectable hepatocellular carcinoma, degradable starch microspheres transarterial chemoembolization represents a safe and effective alternative to more well-established chemoembolization techniques like conventional transarterial chemoembolization and drug-eluting beads transarterial chemoembolization.
- Klíčová slova
- Chemoembolization, Embolization, Hepatocellular carcinoma, Liver cancer,
- MeSH
- chemoembolizace * metody MeSH
- hepatocelulární karcinom * terapie mortalita MeSH
- lidé středního věku MeSH
- lidé MeSH
- mikrosféry MeSH
- nádory jater * terapie mortalita MeSH
- prospektivní studie MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- škrob * aplikace a dávkování MeSH
- výsledek terapie MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- multicentrická studie MeSH
- pozorovací studie MeSH
- Názvy látek
- degradable starch microspheres MeSH Prohlížeč
- škrob * MeSH
Biliary drainage is then one of the necessary procedures to help patients suffering from icterus to reduce serum bilirubin levels and relieve symptoms. The aim of this study was identifying risk factors for survival in patients with cholangiocarcinoma (CCA) treated with percutaneous transhepatic biliary drainage (PTBD) and to develop a simple scoring system predicting survival from PTBD insertion. This single-centre retrospective study included 175 consecutive patients undergoing PTBD for extrahepatic CCA (perihilar and distal). Prognostic factors affecting survival of patients with CCA treated with PTBD were analysed. A multivariate analysis showed that mass forming tumor with mass larger than 5 cm and presence of metastasis at the time of PTBD served as a negative prognostic factor (p = 0.002), better survival was associated with lower preprocedural bilirubin and lower CRP (p = 0.003). Multivariate analysis identified two significant risk factors for 3-month mortality: mass-forming tumors and bilirubin levels exceeding 185 µmol/L. A simple scoring system was developed to predict 3-month mortality after PTBD in patients with advanced CCA, demonstrating 86.3% negative predictive value and 43.2% positive predictive value.
- Klíčová slova
- Biliary malignancy, Biliary stenosis, Metal stent, Percutaneous transhepatic biliary drainage, Prognostic factors, Scoring system,
- MeSH
- bilirubin krev MeSH
- cholangiokarcinom * mortalita patologie terapie chirurgie MeSH
- dospělí MeSH
- drenáž * metody MeSH
- lidé středního věku MeSH
- lidé MeSH
- nádory žlučových cest * mortalita patologie terapie chirurgie MeSH
- prognóza MeSH
- retrospektivní studie MeSH
- rizikové faktory 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
- práce podpořená grantem MeSH
- Názvy látek
- bilirubin MeSH
PURPOSE: TACE induces variable systemic effects by producing factors that promote inflammation, oncogenesis, and angiogenesis. Here we compare concentrations of microRNAs (miR-21, miR-210 and miR-34a) and vascular endothelial growth factor (VEGF) in hepatocellular carcinoma (HCC) patients undergoing TACE with degradable (DSM) and nondegradable (DEB) particles and potential use of these biomarker changes for prediction of patient outcomes. MATERIALS AND METHODS: Overall, 52 patients with HCC treated with DSM TACE (24 patients) and DEB TACE (28 patients) were included in this prospective study. Concentrations of studied biomarkers were measured from blood plasma preprocedurally, immediately (< 90 min) postprocedurally, and 24-h after TACE. Levels were compared between DSM and DEB TACE and correlated with treatment response six and 12 months after the first TACE. RESULTS: Both DSM and DEB TACE elevated plasma levels of miR-21, miR-34a, and miR-210 at 24 h post-procedure compared to baseline levels (FC 1.25-4.0). MiR-34a elevation immediately after TACE was significantly associated with nonprogressive disease compared to those with progressive disease at both six months (FCa: p = 0.014) and 12 months (FCa: p = 0.029) post-TACE. No significant biomarker changes were found between the embolization particle groups. However, VEGF levels showed a decrease only in the DSM TACE group (FC24: p = < 0.001). CONCLUSION: Embolization particle type did not significantly impact miRNA or VEGF changes post-TACE. However, miR-34a elevation immediately after the procedure predicts better patient outcome and may prove useful as a biomarkers for the monitoring of clinical outcomes. LEVEL OF EVIDENCE: Level 3 Prospective cohort study.
- Klíčová slova
- Degradable and nondegradable particles, Hepatocellular carcinoma, Hypoxia, MicroRNA and vascular endothelial growth factor, Transarterial chemoembolization, Tumor suppressor,
- MeSH
- biologické markery krev MeSH
- chemoembolizace * metody MeSH
- hepatocelulární karcinom * terapie krev genetika MeSH
- lidé středního věku MeSH
- lidé MeSH
- mikro RNA * krev MeSH
- nádorové biomarkery * krev MeSH
- nádory jater * terapie genetika krev MeSH
- prospektivní studie MeSH
- senioři MeSH
- vaskulární endoteliální růstový faktor A * krev MeSH
- výsledek terapie MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- biologické markery MeSH
- mikro RNA * MeSH
- MIRN21 microRNA, human MeSH Prohlížeč
- MIRN34 microRNA, human MeSH Prohlížeč
- nádorové biomarkery * MeSH
- vaskulární endoteliální růstový faktor A * MeSH
PURPOSE: To demonstrate advantages of spectral dual-layer computed tomography (CT) in diagnosing pulmonary embolism (PE). To compare D-dimer values in patients with PE and concomitant COVID-19 pneumonia to those in patients without PE and COVID-19 pneumonia. To compare D-dimer values in cases of minor versus extensive PE. METHODS: A monocentric retrospective study of 1500 CT pulmonary angiographies (CTPAs). Three groups of 500 consecutive examinations: 1) using conventional multidetector CT (CTC), 2) using spectral dual-layer CT (CTS), and 3) of COVID-19 pneumonia patients using spectral dual-layer CT (COV). Only patients with known D-dimer levels were enrolled in the study. RESULTS: Prevalence of inconclusive PE findings differed significantly between CTS and CTC (0.8 % vs. 5.4 %, p < 0.001). In all groups, D-dimer levels were significantly higher in PE positive patients than in patients without PE (CTC, 8.04 vs. 3.05 mg/L; CTS, 6.92 vs. 2.57 mg/L; COV, 10.26 vs. 2.72 mg/L, p < 0.001). There were also statistically significant differences in D-dimer values between minor and extensive PE in the groups negative for COVID-19 (CTC, 5.16 vs. 8.98 mg/L; CTS 3.52 vs. 9.27 mg/L, p < 0.001). The lowest recorded D-dimer value for proven PE in patients with COVID-19 pneumonia was 1.19 mg/L. CONCLUSION: CTPAs using spectral dual-layer CT reduce the number of inconclusive PE findings. Plasma D-dimer concentration increases with extent of PE. Cut-off value of D-dimer with 100 % sensitivity for patients with COVID-19 pneumonia could be doubled to 1.0 mg/L. This threshold would have saved 110 (22 %) examinations in our cohort.
- Klíčová slova
- COVID-19, D-dimer, Dual-energy CT, Pulmonary embolism, Spectral CT,
- Publikační typ
- časopisecké články MeSH
Image-guided radiofrequency ablation (RFA) is used to treat focal tumors in the liver and other organs. Despite potential advantages over surgery, hepatic RFA can promote local and distant tumor growth by activating pro-tumorigenic growth factor and cytokines. Thus, strategies to identify and suppress pro-oncogenic effects of RFA are urgently required to further improve the therapeutic effect. Here, the proliferative effect of plasma of Hepatocellular carcinoma or colorectal carcinoma patients 90 min post-RFA was tested on HCC cell lines, demonstrating significant cellular proliferation compared to baseline plasma. Multiplex ELISA screening demonstrated increased plasma pro-tumorigenic growth factors and cytokines including the FGF protein family which uniquely and selectively activated HepG2. Primary mouse and immortalized human hepatocytes were then subjected to moderate hyperthermia in-vitro, mimicking thermal stress induced during ablation in the peri-ablational normal tissue. Resultant culture medium induced proliferation of multiple cancer cell lines. Subsequent non-biased protein array revealed that these hepatocytes subjected to moderate hyperthermia also excrete a similar wide spectrum of growth factors. Recombinant FGF-2 activated multiple cell lines. FGFR inhibitor significantly reduced liver tumor load post-RFA in MDR2-KO inflammation-induced HCC mouse model. Thus, Liver RFA can induce tumorigenesis via the FGF signaling pathway, and its inhibition suppresses HCC development.
- MeSH
- cytokiny MeSH
- fibroblastové růstové faktory MeSH
- hepatocelulární karcinom * patologie MeSH
- indukovaná hypertermie * MeSH
- karcinogeneze MeSH
- katetrizační ablace * MeSH
- lidé MeSH
- myši MeSH
- nádory jater * patologie MeSH
- radiofrekvenční ablace * škodlivé účinky MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- myši MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Research Support, N.I.H., Extramural MeSH
- Názvy látek
- cytokiny MeSH
- fibroblastové růstové faktory MeSH
Developmental cysts are pathological epithelial-lined cavities arising in various organs as a result of systemic or hereditary diseases. Molecular mechanisms involved in the formation of developmental odontogenic cysts (OCs) are not fully understood yet; the cystogenesis of renal cysts originating from the autosomal dominant polycystic kidney disease (ADPKD) has been, however, explored in much greater detail. This narrative review aimed i) to summarize molecular and cellular processes involved in the formation and growth of developmental OCs, especially dentigerous cysts (DCs) and odontogenic keratocysts (OKCs), ii) to find if there are any similarities in their cystogenesis to ADPKD cysts, and, based on that, iii) to suggest potential factors, candidate molecules, and mechanisms that could be involved in the DC formation, thus proposing further research directions. Here we suggest a possible association of developmental OCs with primary cilia disruption and with hypoxia, which have been previously linked with cyst formation in ADPKD patients. This is illustrated on the imagery of tissues from an ADPKD patient (renal cyst) and from developmental OCs, supporting the similarities in cell proliferation, apoptosis, and primary cilia distribution in DC/OKC/ADPKD tissues. Based on all that, we propose a novel hypothesis of OCs formation suggesting a crucial role of mutations associated with the signaling pathways of primary cilia (in particular, Sonic Hedgehog). These can lead to excessive proliferation and formation of cell agglomerates, which is followed by hypoxia-driven apoptosis in the centers of such agglomerates (controlled by molecules such as Hypoxia-inducible factor-1 alpha), leading to cavity formation and, finally, the OCs development. Based on this, we propose future perspectives in the investigation of OC pathogenesis.
- Klíčová slova
- Dentigerous cyst, Developmental odontogenic cyst, Odontogenic keratocyst, Polycystic kidney disease, Polycystin, Primary cilia, Sonic hedgehog pathway,
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
BACKGROUND/AIM: To evaluate the prognostic value of Response Evaluation Criteria In Solid Tumors (RECIST), modified RECIST and volumetric analysis in patients with hepatocellular carcinoma (HCC) treated by transarterial chemoembolization (TACE). PATIENTS AND METHODS: This single-center prospective cohort study included a total of 61 patients with HCC treated by transarterial chemoembolization (TACE). The response of TACE was evaluated on preprocedural and postprocedural CT by two radiologists using RECIST/mRECIST and volumetric response to treatment. Each response assessment method was used to classify the response as progressive disease, stable disease, partial response and complete response. Kaplan-Meier analysis with log-rank test was performed for each method to evaluate its ability to help predict overall survival and progression free survival. Interobserver variability and reproducibility was determined by the Pearson and Spearman correlation coefficients. RESULTS: The median overall survival was 17.1 months and the median progression-free survival was 11.1 months. Volumetric assessment was proved to be a prognostic factor for overall survival (p<0.01) and progression-free survival (p<0.001), contrasting with RECIST and mRECIST. All three methods featured very small interobserver variability (p<0.001 for Pearson and Spearman correlation coefficients). The patients classified as having stable disease had a 3.8-fold higher risk of death than the patients classified as having a complete/partial response (HR=3.82; 95% Confidence Interval (CI)=1.32-11.02; p=0.013) and a 4.5-fold higher risk of progression (HR=4.46; 95% CI=1.72-11.61; p=0.002). CONCLUSION: The prognostic value of volumetric analysis in patients with HCC treated by TACE appears to be superior to RECIST and mRECIST, with a real impact in everyday practice.
- Klíčová slova
- Hepatocellular carcinoma, RECIST, mRECIST, transarterial chemoembolization, volumetric analysis,
- MeSH
- chemoembolizace * metody MeSH
- hepatocelulární karcinom * diagnostické zobrazování terapie MeSH
- lidé MeSH
- nádory jater * terapie MeSH
- prospektivní studie MeSH
- reprodukovatelnost výsledků MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
PURPOSE: To prove feasibility and safety of percutaneous endoluminal radiofrequency ablation (eRFA) using a monopolar approach in treatment of occluded biliary stent in malignancy. MATERIALS AND METHODS: The study included 11 patients with occluded biliary metal stent that had been implanted due to malignant biliary obstruction. All underwent metal stent recanalization by percutaneous eRFA in monopolar setting. Sixteen eRFA procedures were performed under fluoroscopic guidance with an EndoHPB 8F radiofrequency ablation catheter. The effect of stent recanalization was assessed based upon change from pre- to post-procedural diameter of the patent lumen of the metal stent (Wilcoxon test), primary and secondary stent patency (compared by log-rank test), catheter-free period, and overall survival. Adverse events were evaluated according to Common Terminology Criteria for Adverse Events (CTCEA) 4.0. RESULTS: Recanalization of the metal stent by monopolar radiofrequency ablation was successful in all 11 patients. Diameter of the patent lumen of the stent significantly widened after the eRFA inside the stent (median 2 vs. 7 mm, p = 0.003). Grade 1 complications were observed in one-third of procedures. Median stent patency after recanalization by eRFA was non-inferior to primary metal stent patency (154 vs. 161 days, p = 0.27). Median catheter-free survival and overall survival after stent recanalization were 149 and 210 days, respectively. CONCLUSION: Endoluminal radiofrequency ablation in monopolar setting was shown to be a feasible and safe method for recanalization of occluded biliary metal stents. LEVEL OF EVIDENCE: Level 4, Case Series.
- Klíčová slova
- Biliary malignancy, Biliary stenosis, Intraductal ablation, Metal stent, Monopolar technique, Radiofrequency ablation,
- MeSH
- cholestáza * diagnostické zobrazování etiologie chirurgie MeSH
- katetrizační ablace * metody MeSH
- lidé MeSH
- nádory žlučových cest * chirurgie MeSH
- radiofrekvenční ablace * MeSH
- retrospektivní studie MeSH
- stenty škodlivé účinky MeSH
- studie proveditelnosti MeSH
- výsledek terapie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
BACKGROUND: Acromegaly is a disorder associated with hypersecretion of growth hormone, most usually caused by a pituitary adenoma. Dysmotility of the gastrointestinal tract has been reported in acromegalic patients. Achalasia is a disorder characterized by aperistalsis of the oesophagus with incomplete lower oesophageal sphincter relaxation and whose aetiology remains unknown. Mutations in some genes have previously been associated with the development of acromegaly or achalasia. The study aims were to analyse mutations in selected genes in a woman having both of these diseases, to identify their aetiological factors, and to suggest explanations for the co-incidence of acromegaly and achalasia. METHODS AND RESULTS: A female patient with acromegaly, achalasia, and a multinodular thyroid gland with hyperplastic colloid nodules underwent successful treatment of achalasia via laparoscopic Heller myotomy, a thyroidectomy was performed, and the pituitary macroadenoma was surgically excised via transnasal endoscopic extirpation. Germline DNA from the leukocytes was analysed by sequencing methods for a panel of genes. No pathogenic mutation in AAAS, AIP, MEN1, CDKN1B, PRKAR1A, SDHB, GPR101, and GNAS genes was found in germline DNA. The somatic mutation c.601C>T/p.R201C in the GNAS gene was identified in DNA extracted from a tissue sample of the pituitary macroadenoma. CONCLUSIONS: We here describe the first case report to our knowledge of a patient with both acromegaly and achalasia. Association of acromegaly and soft muscle tissue hypertrophy may contribute to achalasia's development. If one of these diagnoses is determined, the other also should be considered along with increased risk of oesophageal and colorectal malignancy.
- Klíčová slova
- AAAS, GNAS, GPR101, achalasia, acromegaly, autoimmune syndrome, gene, mutation, pituitary tumour,
- MeSH
- achalázie jícnu * komplikace genetika MeSH
- akromegalie * komplikace genetika MeSH
- DNA MeSH
- incidence MeSH
- lidé MeSH
- nádory hypofýzy * genetika MeSH
- Check Tag
- lidé MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- kazuistiky MeSH
- Názvy látek
- DNA MeSH