Colorectal liver metastases (CRLM) are a major indication for liver surgery in Europe, highlighting the need for standardized knowledge and training in surgical oncology. The European Society of Surgical Oncology (ESSO) has updated its core curriculum to provide a structured framework for education. Previous publications have addressed pancreatic, hepatocellular, and biliary tract cancers to support candidates preparing for the European Board of Surgery Qualification (EBSQ) exams in Surgical Oncology and Hepato-Pancreato-Biliary Surgery. However, a dedicated guide for CRLM remains absent. This article aims to fill that gap by offering a structured reference on CRLM, covering epidemiology, staging, genetics, and diagnosis of metastatic colorectal cancer. It also outlines multidisciplinary treatment strategies, including systemic, surgical, interventional, and palliative approaches. A structured literature review was conducted using PubMed to identify the most updated (inter)national management guidelines, prioritizing recent multicentre studies, systematic reviews, and meta-analyses published from January 2020 to January 2025. By bridging the gap between the ESSO core curriculum and detailed subspecialty training, this guide provides an essential resource for hepatobiliary surgeons and surgical oncologists. It serves as a valuable tool for those preparing for board examinations while promoting a standardized approach to CRLM education and management across Europe.
- Klíčová slova
- Colorectal cancer, Core curriculum, ESSO, Liver metastases, Surgical oncology, UEMS,
- MeSH
- chirurgická onkologie * výchova MeSH
- hepatektomie výchova MeSH
- kolorektální nádory * patologie MeSH
- kurikulum * MeSH
- lidé MeSH
- nádory jater * sekundární terapie diagnóza chirurgie epidemiologie genetika MeSH
- společnosti lékařské MeSH
- staging nádorů MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
- Geografické názvy
- Evropa MeSH
Colorectal cancer is a leading malignancy, with synchronous colorectal liver metastases (CRLM) presenting in 20 % of patients. Resection remains the gold standard treatment for CRLMs, significantly improving survival outcomes. However, the optimal timing of resection of these synchronous lesions - simultaneous versus staged - remains controversial. This systematic review and meta-analysis synthesises data exclusively from propensity-score-matched and prospective studies. A comprehensive search of five databases identified 11 eligible studies, encompassing 2884 patients. Of these, 1453 underwent simultaneous resection, and 1431 underwent staged procedures. The primary outcome was 5-year overall survival (OS), with secondary outcomes including disease-free survival (DFS), surgical morbidity, operating time, and length of hospital stay. Meta-analysis demonstrated no significant difference in 5-year OS between simultaneous and staged resection groups (odds ratio [OR] 1.10, 95 % CI 0.75-1.61; p = 0.83). However, simultaneous resection was associated with significantly higher 3-year DFS (OR 1.67, 95 % CI 1.28-2.17; p = 0.0001) but also increased major surgical complications (Clavien-Dindo ≥ III: OR 1.32, 95 % CI 1.03-1.68; p = 0.03). This review highlights a lack of oncological advantage for simultaneous resection, coupled with higher morbidity, suggesting its use should be limited to select patients with low surgical risk. The findings underscore the need for well-powered, randomised trials to confirm these conclusions, as well as assess quality of life and economic outcomes, however delivering such trials in this patient cohort brings unique challenges. Until such data are available, clinical decision-making should remain individualised, guided by multidisciplinary discussion and available local expertise.
- Klíčová slova
- Colorectal cancer, Liver metastases, Meta-analysis, Simultaneous resection, Staged resection, Synchronous metastases,
- MeSH
- časové faktory MeSH
- délka operace MeSH
- délka pobytu MeSH
- hepatektomie * metody MeSH
- kolorektální nádory * patologie MeSH
- lidé MeSH
- míra přežití MeSH
- nádory jater * chirurgie sekundární MeSH
- pooperační komplikace epidemiologie MeSH
- přežití bez známek nemoci MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- metaanalýza MeSH
- systematický přehled MeSH
Prognostic value of T-cells between primary colorectal cancer (pCRC) and its paired synchronous and metachronous liver metastasis (LM) is underinvestigated and is the subject of the present study. We enrolled into this retrospective cohort study patients, who underwent resection of both pCRC and synchronous LM (N = 55) or metachronous LM (N = 44). After immunohistochemical staining for CD3+, CD8+, and CD45R0+ whole slides were scanned and T-cell densities were quantified using QuPath software in tumor center (TC), inner margin (IM), outer margin (OM), and peritumor zone (PT) of pCRC and LM. High densities of CD8+ T-cells in TC, OM and PT of synchronous LM were associated with longer disease-free survival (DFS). Greater densities of CD3+ T-cells in IM and PT and CD8+ T-cells in IM, OM and PT in synchronous LM over pCRC were associated with longer DFS. Greater densities of CD8+ T-cells in the TC and IM and CD3+ T-cells in the IM of pCRC were found in the metachronous over synchronous group. The first novel finding demonstrated that high density of CD8+ T cells in synchronous LM were associated with favorable outcome. The second finding of high CD8+ cell density in pCRC in metachronous over synchronous CRC may provide a mechanistic basis for the delay of metastatic spread. Both findings could be applied clinically with own reference values.
- Klíčová slova
- colorectal cancer, survival, synchronous and metachronous liver metastases, tumor‐infiltrating lymphocytes,
- MeSH
- CD8-pozitivní T-lymfocyty * imunologie patologie MeSH
- dospělí MeSH
- kolorektální nádory * patologie imunologie mortalita chirurgie MeSH
- lidé středního věku MeSH
- lidé MeSH
- mnohočetné primární nádory * patologie imunologie MeSH
- nádory jater * sekundární imunologie mortalita MeSH
- prognóza MeSH
- retrospektivní studie MeSH
- sekundární malignity * imunologie patologie MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- T-lymfocyty * imunologie patologie 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
INTRODUCTION: Pancreatic cancer is one of the most aggressive tumors diagnosed in local-ly advanced or metastatic stage in more than half of the cases. The standard of care is a systemic chemotherapy but the prognosis of metastatic patients remains extremely poor with a median overall survival less than one year. However, there is increasing evidence of surgery treatment benefit in a carefully selected oligometastatic cases. -Because oligometastatic pancreatic cancer is rare, there is a lack of robust clinical trials defining strategy, efficacy and safety of this procedure. PATIENT CONCERNS: A 77-year-old man presented with a mass in the tail of the pancreas and solitary liver metastasis. After four cycles of chemotherapy, distal pancreatectomy with liver metastasectomy was performed, and the tissues were histologically examined. The complete pathological response was found in the primary tumor and residual adenocarcinoma in liver metastasis. OUTCOMES: The patient is alive without recurrency more than two years from the diagnosis.
- Klíčová slova
- Pancreas, cancer, carcinoma, oligometastatic, pancreas, resection,
- MeSH
- adenokarcinom sekundární farmakoterapie chirurgie MeSH
- lidé MeSH
- metastázektomie MeSH
- nádory jater * sekundární farmakoterapie chirurgie MeSH
- nádory slinivky břišní * patologie farmakoterapie chirurgie sekundární MeSH
- neoadjuvantní terapie * MeSH
- pankreatektomie * MeSH
- protokoly protinádorové kombinované chemoterapie terapeutické užití MeSH
- senioři MeSH
- Check Tag
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- Publikační typ
- časopisecké články MeSH
- kazuistiky MeSH
Chronic diarrhea is a significant challenge in clinical practice because of its high prevalence and various causes. Comprehensive clinical assessment and stepwise laboratory approach are crucial for an accurate diagnosis. This report presents a case of an adult woman who experienced chronic watery diarrhea, complicated by renal impairment and multiple electrolyte imbalances, including hypokalemia, hypophosphatemia, and metabolic acidosis. The diagnosis of a vasoactive intestinal polypeptide-secreting tumor (VIPoma) with liver metastases was confirmed by elevated serum levels of a vasoactive intestinal polypeptide (VIP) and imaging findings of a pancreatic mass with multiple hepatic lesions. Preoperative management, including fluid rehydration, electrolyte correction, and somatostatin analog therapy, significantly improved her clinical symptoms. Subsequent surgical tumor removal and radiofrequency ablation of the hepatic lesions resulted in complete resolution of symptoms and normalized VIP levels. This case emphasizes the importance of early recognition of this rare tumor in patients with chronic diarrhea to improve clinical outcomes.
- Klíčová slova
- VIPoma, WDHA syndrome, chronic watery diarrhea, functional neuroendocrine tumor, vasoactive intestinal polypeptide,
- MeSH
- chronická nemoc MeSH
- diareogenní nádor * komplikace diagnóza MeSH
- lidé středního věku MeSH
- lidé MeSH
- nádory jater sekundární komplikace MeSH
- nádory slinivky břišní * komplikace MeSH
- průjem * etiologie MeSH
- vazoaktivní intestinální peptid krev MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- kazuistiky MeSH
- Názvy látek
- vazoaktivní intestinální peptid MeSH
It is estimated that only 0.02% of disseminated tumour cells are able to seed overt metastases1. While this suggests the presence of environmental constraints to metastatic seeding, the landscape of host factors controlling this process remains largely unclear. Here, combining transposon technology2 and fluorescence niche labelling3, we developed an in vivo CRISPR activation screen to systematically investigate the interactions between hepatocytes and metastatic cells. We identify plexin B2 as a critical host-derived regulator of liver colonization in colorectal and pancreatic cancer and melanoma syngeneic mouse models. We dissect a mechanism through which plexin B2 interacts with class IV semaphorins on tumour cells, leading to KLF4 upregulation and thereby promoting the acquisition of epithelial traits. Our results highlight the essential role of signals from the liver parenchyma for the seeding of disseminated tumour cells before the establishment of a growth-promoting niche. Our findings further suggest that epithelialization is required for the adaptation of CRC metastases to their new tissue environment. Blocking the plexin-B2-semaphorin axis abolishes metastatic colonization of the liver and therefore represents a therapeutic strategy for the prevention of hepatic metastases. Finally, our screening approach, which evaluates host-derived extrinsic signals rather than tumour-intrinsic factors for their ability to promote metastatic seeding, is broadly applicable and lays a framework for the screening of environmental constraints to metastasis in other organs and cancer types.
- MeSH
- CRISPR-Cas systémy * genetika MeSH
- fluorescence MeSH
- hepatocyty * metabolismus cytologie patologie MeSH
- játra * cytologie metabolismus patologie MeSH
- kolorektální nádory patologie metabolismus MeSH
- Krüppel-like faktor 4 metabolismus MeSH
- lidé MeSH
- melanom metabolismus patologie MeSH
- metastázy nádorů * farmakoterapie patologie prevence a kontrola MeSH
- modely nemocí na zvířatech MeSH
- myši MeSH
- nádorové buněčné linie MeSH
- nádory jater * farmakoterapie metabolismus patologie prevence a kontrola sekundární MeSH
- nádory slinivky břišní metabolismus patologie MeSH
- proteiny nervové tkáně * antagonisté a inhibitory metabolismus MeSH
- semaforiny antagonisté a inhibitory metabolismus MeSH
- transpozibilní elementy DNA MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- mužské pohlaví MeSH
- myši MeSH
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- KLF4 protein, human MeSH Prohlížeč
- Klf4 protein, mouse MeSH Prohlížeč
- Krüppel-like faktor 4 MeSH
- PLXNB2 protein, human MeSH Prohlížeč
- Plxnb2 protein, mouse MeSH Prohlížeč
- proteiny nervové tkáně * MeSH
- semaforiny MeSH
- transpozibilní elementy DNA MeSH
BACKGROUND: Uveal melanoma is a rare cancer, in which metastases occur in approximately one half of cases. In metastatic disease, the prognosis is unfavorable and the median of survival does not exceed 6 months. Effective treatment options were very limited up to date. Tebentafusp is a bispecific fusion protein, which as the first drug proved efficacy in uveal melanoma. CASE: The patient was referred for suspected uveal melanoma of the left eye. She was treated for Hodgkin's disease in the past. Primarily, the tumor was treated by radiosurgery with radiotherapy of a small lesion of the vertebral body. However, later the patient had to undergo bulbus enucleation with confirmation of a large tumor category pT4b. PET/CT revealed metastases of the bones and the liver; simultaneously, haplotype A*02: 01 was confirmed. The patient underwent radiotherapy of the sternum and later, after confirmation of payment from the health insurance company, she started treatment with tebentafusp. The first three doses were administered during admission to the hospital, with a need to treat cytokine release syndrome by corticosteroids. Later, the administration was performed in an out-patient regimen, without complications, except for a transient elevation of transaminases. The first CT restaging confirmed stable disease; however, the second restaging confirmed a new osteolytic lesion in the processus of Th11. Because of progression, the treatment with tebentafusp was withdrawn after 6 months. Unfortunately, the lesion could not be treated by radiotherapy. Two months later, the patient was urgently admitted to the hospital because of right-sided hemiplegia; MRI revealed bleeding metastatic lesion in the brain stem. CONCLUSION: In this case report, we present the case of the first patient treated with this drug in the Czech Republic.
- Klíčová slova
- tebentafusp, treatment, type 2 diabetes, uveal melanoma,
- MeSH
- lidé MeSH
- melanom * sekundární terapie MeSH
- nádory jater sekundární terapie MeSH
- nádory kostí sekundární terapie MeSH
- nádory uvey * patologie terapie MeSH
- protinádorové látky terapeutické užití MeSH
- rekombinantní fúzní proteiny terapeutické užití MeSH
- uveální melanom MeSH
- Check Tag
- lidé MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- kazuistiky MeSH
- Geografické názvy
- Česká republika MeSH
- Názvy látek
- protinádorové látky MeSH
- rekombinantní fúzní proteiny MeSH
BACKGROUND/AIM: Patients with unresectable liver colorectal cancer metastases are treated with neoadjuvant chemotherapy often accompanied by biological therapy aimed at reducing the mass of metastases and thus increasing the chances of resectability. Bevacizumab comprises an anti-VEGF (vascular endothelial growth factor) humanized IgG monoclonal antibody that is used for biological therapy purposes. It acts to inhibit angiogenesis, thereby slowing down the growth of metastases. Due to its being administered systematically, bevacizumab also exerts an effect on the surrounding healthy liver parenchyma and potentially limits the process of neovascularization and thus regeneration of the liver. Since the remnant liver volume forms an important factor in postoperative morbidity and mortality following a major hepatectomy, we decided to study the effect of bevacizumab on vascular and biliary microarchitecture in healthy liver parenchyma and its ability to regenerate following major hepatectomy. MATERIALS AND METHODS: We performed an experiment employing a large animal model where a total of 16 piglets were divided into two groups (8 piglets in the control group and 8 piglets in the experimental group with bevacizumab). All the animals were subjected to major hepatectomy and the experimental group was given bevacizumab prior to hepatectomy. All the animals were sacrificed after 4 weeks. We performed biochemical analyses at regular time intervals during the follow-up period. Histological examination of the liver tissue was performed following sacrifice of the animals. RESULTS: No statistical difference was shown between groups in terms of the biochemical and immunohistochemical parameters. The histological examination of the regenerating liver tissue revealed the higher length density of sinusoids in the experimental group. CONCLUSION: Bevacizumab does not act to impair liver regeneration following hepatectomy.
- Klíčová slova
- Bevacizumab, anti-VEGF, hepatectomy, liver regeneration,
- MeSH
- bevacizumab farmakologie terapeutické užití MeSH
- hepatektomie MeSH
- humanizované monoklonální protilátky farmakologie terapeutické užití MeSH
- kolorektální nádory * farmakoterapie patologie chirurgie MeSH
- lidé MeSH
- modely nemocí na zvířatech MeSH
- nádory jater * farmakoterapie sekundární chirurgie MeSH
- patologická angiogeneze farmakoterapie MeSH
- prasata MeSH
- regenerace jater MeSH
- vaskulární endoteliální růstový faktor A MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- bevacizumab MeSH
- humanizované monoklonální protilátky MeSH
- vaskulární endoteliální růstový faktor A MeSH
Colorectal cancer is a prevalent disease worldwide, with more than 50% of patients developing metastases to the liver. Despite advances in improving resectability, most patients present with non-resectable colorectal liver metastases requiring palliative systemic therapy and locoregional disease control strategies. There is a growing interest in the use of liver transplantation to treat non-resectable colorectal liver metastases in well selected patients, leading to a surge in the number of studies and prospective trials worldwide, thereby fuelling the emerging field of transplant oncology. The interdisciplinary nature of this field requires domain-specific evidence and expertise to be drawn from multiple clinical specialities and the basic sciences. Importantly, the wider societal implication of liver transplantation for non-resectable colorectal liver metastases, such as the effect on the allocation of resources and national transplant waitlists, should be considered. To address the urgent need for a consensus approach, the International Hepato-Pancreato-Biliary Association commissioned the Liver Transplantation for Colorectal liver Metastases 2021 working group, consisting of international leaders in the areas of hepatobiliary surgery, colorectal oncology, liver transplantation, hepatology, and bioethics. The aim of this study was to standardise nomenclature and define management principles in five key domains: patient selection, evaluation of biological behaviour, graft selection, recipient considerations, and outcomes. An extensive literature review was done within the five domains identified. Between November, 2020, and January, 2021, a three-step modified Delphi consensus process was undertaken by the workgroup, who were further subgrouped into the Scientific Committee, Expert Panel, and Transplant Centre Representatives. A final consensus of 44 statements, standardised nomenclature, and a practical management algorithm is presented. Specific criteria for clinico-patho-radiological assessments with molecular profiling is crucial in this setting. After this, the careful evaluation of biological behaviour with bridging therapy to transplantation with an appropriate assessment of the response is required. The sequencing of treatment in synchronous metastatic disease requires special consideration and is highlighted here. Some ethical dilemmas within organ allocation for malignant indications are discussed and the role for extended criteria grafts, living donor transplantation, and machine perfusion technologies for non-resectable colorectal liver metastases are reviewed. Appropriate immunosuppressive regimens and strategies for the follow-up and treatment of recurrent disease are proposed. This consensus guideline provides a framework by which liver transplantation for non-resectable colorectal liver metastases might be safely instituted and is a meaningful step towards future evidenced-based practice for better patient selection and organ allocation to improve the survival for patients with this disease.
- MeSH
- adenokarcinom diagnóza sekundární chirurgie MeSH
- delfská metoda MeSH
- klinické rozhodování metody MeSH
- kolorektální nádory patologie MeSH
- lidé MeSH
- nádory jater diagnóza sekundární chirurgie MeSH
- prognóza MeSH
- transplantace jater metody normy MeSH
- výběr pacientů MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- konsensus - konference MeSH
- směrnice pro lékařskou praxi MeSH
Cholangiocarcinoma (CCA) is a liver malignancy associated with a poor prognosis. Its main subtypes are peripheral/intrahepatic and hilar/extrahepatic CCA. Several molecular, morphological and clinical similarities between hilar/extrahepatic CCA and pancreatic ductal adenocarcinoma (PDAC) have been described. FOXF1 is a transcription factor which has been described to have prognostic significance in various tumors and it is involved in the development of bile ducts. The aim of this study is to determine occurrence of nuclear expression of FOXF1 in both subtypes of CCA and metastatic PDAC and assess its potential usefulness as a diagnostic marker. Secondary aims were to investigate the use of C-reactive protein (CRP) immunohistochemistry for diagnosing intrahepatic peripheral CCA and the significance of histological features in CCA subtypes. 32 archive specimens of CCA, combined hepatocellular carcinoma-CCA (HCC-CCA) and liver metastasis of PDAC were stained by FOXF1 and CRP immunohistochemistry and evaluated to determine histological pattern. The CCAs were classified radiologically into peripheral/intrahepatic and hilar subtype. Using Fisher exact test, we identified nuclear FOXF1 as a fairly specific (87%) but insensitive (65%) marker of hilar and extrahepatic CCA and metastatic PDAC (p = 0.005). CRP immunohistochemistry was characterized by a high sensitivity and specificity, of 79% and 88%, respectively (p = 0.001). We did not identify any histomorphological features associated with either types of CCA or metastatic PDAC. As a conclusion of novel finding, FOXF1 immunohistochemistry may be regarded as a specific but insensitive marker of hilar/extrahepatic CCA and metastatic PDAC and it may help distinguish them from peripheral CCA.
- Klíčová slova
- Foxf1, cholangiocarcinoma, extrahepatic, hilar, intrahepatic cholangiocarcinoma, peripheral,
- MeSH
- dospělí MeSH
- duktální karcinom slinivky břišní metabolismus sekundární MeSH
- forkhead transkripční faktory metabolismus MeSH
- hepatocelulární karcinom metabolismus patologie MeSH
- imunohistochemie MeSH
- Klatskinův nádor metabolismus patologie MeSH
- lidé středního věku MeSH
- lidé MeSH
- míra přežití MeSH
- nádorové biomarkery metabolismus MeSH
- nádory jater metabolismus sekundární MeSH
- nádory slinivky břišní metabolismus patologie MeSH
- nádory žlučových cest metabolismus patologie MeSH
- následné studie MeSH
- prognóza 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
- Názvy látek
- forkhead transkripční faktory MeSH
- FOXF1 protein, human MeSH Prohlížeč
- nádorové biomarkery MeSH