- Keywords
- durvalumab,
- MeSH
- Cholangiocarcinoma drug therapy MeSH
- Carcinoma, Hepatocellular drug therapy MeSH
- Antibodies, Monoclonal, Humanized pharmacology therapeutic use MeSH
- Immunotherapy * methods MeSH
- Immune Checkpoint Inhibitors * administration & dosage pharmacology classification therapeutic use MeSH
- Clinical Studies as Topic MeSH
- Humans MeSH
- Carcinoma, Non-Small-Cell Lung drug therapy MeSH
- Check Tag
- Humans MeSH
- Publication type
- Review MeSH
- Keywords
- durvalumab,
- MeSH
- Cholangiocarcinoma drug therapy MeSH
- Immune Checkpoint Inhibitors * administration & dosage pharmacology classification therapeutic use MeSH
- Humans MeSH
- Carcinoma, Non-Small-Cell Lung drug therapy MeSH
- Check Tag
- Humans MeSH
- Publication type
- Practice Guideline MeSH
BACKGROUND: Extended liver resection is the only treatment option for perihilar cholangiocarcinoma (pCCA). Bile salts and the gut hormone FGF19, both promoters of liver regeneration (LR), have not been investigated in patients undergoing resection for pCCA. We aimed to evaluate the bile salt-FGF19 axis perioperatively in pCCA and study its effects on LR. METHODS: Plasma bile salts, FGF19, and C4 (bile salt synthesis marker) were assessed in patients with pCCA and controls (colorectal liver metastases), before and after resection on postoperative days (PODs) 1, 3, and 7. Hepatic bile salts were determined in intraoperative liver biopsies. RESULTS: Partial liver resection in pCCA elicited a sharp decline in bile salt and FGF19 plasma levels on POD 1 and remained low thereafter, unlike in controls, where bile salts rose gradually. Preoperatively, suppressed C4 in pCCA normalized postoperatively to levels similar to those in the controls. The remnant liver volume and postoperative bilirubin levels were negatively associated with postoperative C4 levels. Furthermore, patients who developed postoperative liver failure had nearly undetectable C4 levels on POD 7. Hepatic bile salts strongly predicted hyperbilirubinemia on POD 7 in both groups. Finally, postoperative bile salt levels on day 7 were an independent predictor of LR. CONCLUSIONS: Partial liver resection alters the bile salt-FGF19 axis, but its derailment is unrelated to LR in pCCA. Postoperative monitoring of circulating bile salts and their production may be useful for monitoring LR.
- MeSH
- Fibroblast Growth Factors * blood MeSH
- Hepatectomy * MeSH
- Liver metabolism surgery MeSH
- Klatskin Tumor * surgery pathology blood MeSH
- Middle Aged MeSH
- Humans MeSH
- Bile Duct Neoplasms * surgery pathology blood MeSH
- Liver Regeneration * physiology MeSH
- Aged MeSH
- Case-Control Studies MeSH
- Bile Acids and Salts * blood metabolism MeSH
- Check Tag
- Middle Aged MeSH
- Humans MeSH
- Male MeSH
- Aged MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
Fosfor je jedním z tzv. makroprvků a najdeme jej ve všech živých buňkách. Při vyšetření elektrolytů bývá fosfát často přehlížen a vyšetřován je spíše v podezření na tzv. syndrom nádorového rozpadu, kdy bývá typicky zvýšen. Hypofosfatemie je ovšem naproti tomu často podceňována. Fosfát hraje přitom důležitou roli v těle při tvorbě energie (ve formě ATP - adenosin trifosfátu), výstavbě kostí a svou úlohu má i v regulaci afinity hemoglobinu ke kyslíku jako 2,3-difosfoglycerát. S následující kazuistikou z německé kliniky bych chtěl upozornit na význam měření fosfatemie a benefit případné substituce pro naše pacienty.
Phosphorus is one of the so-called macronutrients and is found in all living cells. Phosphate is often overlooked during electrolyte testing and is more likely to be examined in suspected cases of Tumor lysis syndrome (TLS), where it is typically elevated. However, hypophosphatemia is often underestimated. Yet phosphate plays an important role in the body in energy production (in the form of ATP - adenosine triphosphate), bone building and also has a role in regulating the affinity of haemoglobin for oxygen as 2,3-bisphosphoglycerate. With the following case report, I would like to highlight the importance of measuring phosphatemia and the benefit of possible substitution for our patients.
- MeSH
- Cholangiocarcinoma complications MeSH
- Hypophosphatemia * diagnosis etiology therapy MeSH
- Humans MeSH
- Water-Electrolyte Imbalance diagnosis etiology therapy MeSH
- Check Tag
- Humans MeSH
- Female MeSH
- Publication type
- Case Reports MeSH
Cholangiocelulární karcinom, i když se nejedná o častou malignitu, představuje vzhledem k vysoké mortalitě s ním spojené závažný medicínský problém. Pacienti v časných stadiích po potenciálně kurativním chirurgickém výkonu jsou indikováni k pooperační terapii s cílem snížit riziko lokoregionálního nebo vzdáleného relapsu. Nicméně většina pacientů s cholangiocelulárním karcinomem je diagnostikována v lokoregionálním pokročilém a/nebo metastatickém stadiu. Standardem léčby pro tyto pacienty je systémová terapie. Po letech stagnace je i v této populaci pacientů posun ke zlepšení přežití s využitím imunoterapie. Současně prohlubování poznatků o molekulární biologii onemocnění umožňuje volit léčbu na míru konkrétnímu pacientovi dle přítomnosti specifické targetabilní alterace. Článek poskytuje přehled aktuálních možností terapie tohoto onemocnění.
Cholangiocellular carcinoma represents major medical issue owing to its high mortality rate, despite not being frequent malignancy. Patients diagnosed at early stages are treated with postoperative treatment after surgery with the aim to decrease rate of locoregionanal or distant relapse. Nevertheless, majority of patients are diagnosed in locoregionaly advanced and/or metastatic stage. These patients are treated with systemic treatment. After years of stagnation there is proven survival benefit with the use of immunotherapy. Moreover, due to our better understanding of molecular biology of disease, we are able to better tailor treatment based on presence of targetable alteration. We provide an overview of current treatment options for cholangiocarcinoma across stages.
- MeSH
- Cholangiocarcinoma * therapy MeSH
- Immunotherapy methods MeSH
- Humans MeSH
- Antineoplastic Combined Chemotherapy Protocols MeSH
- Randomized Controlled Trials as Topic MeSH
- Check Tag
- Humans MeSH
- Publication type
- Review MeSH
V rámci paliativní léčby cholangiocelulárního karcinomu byla donedávna široce využívána chemoterapie, zejména režimy cisplatina + gemcitabin a FOLFOX. V poslední době došlo k výraznému rozšíření možností léčby cholangiocelulárního karcinomu se specifickými mutacemi – u nádorů s fúzí genu FGFR byla prokázána účinnost tyrosinkinázového inhibitoru FGFR1–3 pemigatinibu, u nádorů s aktivační mutací IDH1 byl účinný ivosidenib a u HER2-pozitivních nádorů byl pozorován přínos anti-HER2 léčby (pertuzumab + trastuzumab, zanidatamab). Ukazuje se rovněž, že část pacientů s pokročilým cholangiocelulárním adenokarcinomem by mohla být úspěšně léčena checkpoint inhibitory (CPI): v této souvislosti přinesla robustní data studie TOPAZ-1, ve které vedlo přidání CPI durvalumabu k chemoterapii cisplatina + gemcitabin k signifikantnímu prodloužení přežití bez progrese i celkového přežití pacientů, aniž by přitom došlo k významnějšímu nárůstu toxicity léčby.
Until recently, chemotherapy has been widely used in the palliative treatment of cholangiocellular carcinoma, especially cisplatin + gemcitabine and FOLFOX regimens. Lately, there has been a significant expansion of treatment options for cholangiocellular carcinoma with specific mutations – in tumours with the FGFR gene fusion, efficacy of the FGFR1–3 tyrosine kinase inhibitor pemigatinib has been shown, in tumours with activating IDH1 mutations, ivosidenib has been beneficial, and in HER2-positive tumours, the efficacy of anti-HER2 therapy (pertuzumab + trastuzumab, zanidatamab) has been observed. It also seems, that a proportion of patients with advanced cholangiocellular adenocarcinoma could be successfully treated with checkpoint inhibitors (CPIs): in this context, the TOPAZ-1 trial provided robust data, in which the addition of the CPI durvalumab to cisplatin + gemcitabine chemotherapy led to a significant increase in progressionfree survival as well as overall survival of the patients, without a marked increase in treatment toxicity.
- MeSH
- Cholangiocarcinoma * drug therapy MeSH
- Cisplatin pharmacology therapeutic use MeSH
- Gemcitabine pharmacology therapeutic use MeSH
- Humans MeSH
- Antibodies, Monoclonal pharmacology therapeutic use MeSH
- Antineoplastic Combined Chemotherapy Protocols MeSH
- Randomized Controlled Trials as Topic MeSH
- Check Tag
- Humans MeSH
- Keywords
- mutace genu IDH1, Ivosidenib,
- MeSH
- Cholangiocarcinoma * drug therapy MeSH
- Humans MeSH
- Survival Rate MeSH
- Randomized Controlled Trials as Topic MeSH
- Check Tag
- Humans MeSH
- Keywords
- durvalumab,
- MeSH
- Cholangiocarcinoma * surgery drug therapy MeSH
- Immunotherapy MeSH
- Humans MeSH
- Check Tag
- Humans MeSH
- Publication type
- Review MeSH
