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Fibrolamellar carcinoma (FLC) is a rare, lethal, early-onset liver cancer with a critical need for new therapeutics. The primary driver in FLC is the fusion oncoprotein, DNAJ-PKAc, which remains challenging to target therapeutically. It is critical, therefore, to expand understanding of the FLC molecular landscape to identify druggable pathways/targets. Here, we perform the most comprehensive integrative proteo-metabolomic analysis of FLC. We also conduct nutrient manipulation, respirometry analyses, as well as key loss-of-function assays in FLC tumor tissue slices from patients. We propose a model of cellular energetics in FLC pointing to proline anabolism being mediated by ornithine aminotransferase hyperactivity and ornithine transcarbamylase hypoactivity with serine and glutamine catabolism fueling the process. We highlight FLC's potential dependency on voltage-dependent anion channel (VDAC), a mitochondrial gatekeeper for anions including pyruvate. The metabolic rewiring in FLC that we propose in our model, with an emphasis on mitochondria, can be exploited for therapeutic vulnerabilities.
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Aminoácidos , Carcinoma Hepatocelular , Metabolômica , Mitocôndrias , Humanos , Mitocôndrias/metabolismo , Carcinoma Hepatocelular/metabolismo , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/patologia , Metabolômica/métodos , Aminoácidos/metabolismo , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/patologia , Canais de Ânion Dependentes de Voltagem/metabolismo , Canais de Ânion Dependentes de Voltagem/genética , Proteômica/métodos , FemininoRESUMO
Fibrolamellar hepatocellular carcinoma (FLC) is a rare form of primary liver cancer that predominantly affects adolescents and young adults with no history of cirrhosis. Surgical resection is a potentially curative treatment option, but the optimal duration of surveillance after a potentially curative surgical resection is not known. Here, we present a case of a patient with FLC who developed a recurrence of FLC nearly two decades after resection of the primary tumor. Although the optimal duration of imaging surveillance for FLC is not known, this case report provides initial evidence that long-term surveillance in patients with FLC who have received curative intent surgery is warranted.
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BACKGROUND: Robotic surgery has emerged as a promising approach for managing complex hepatic malignancies. This report presents a case of a single-port robotic liver resection for a patient with recurrent hepatocellular carcinoma (HCC) and metastases, focusing on the surgical technique and outcomes. METHOD: An 18-year-old female with a history of left hepatectomy for fibrolamellar HCC underwent robotic liver resection using the Da Vinci SP Surgical System. The procedure entailed excising a 30 mm tumor in liver segment 4 (Sg4) along with peritoneal metastases in the superior pole of the spleen and cardiophrenic lymph node metastasis. Surgical techniques comprised adhesiolysis, resection of the peritoneal nodule, Sg4 partial liver resection, and excision of the cardiophrenic lymph node. RESULTS: The operative time was 310 min, with a blood loss of 37 mL. The patient experienced an uneventful postoperative course and was discharged home after 8 days. Partial liver resection of Sg4 revealed a moderately differentiated HCC with negative resection margins. Additionally, excision of peritoneal metastases in the superior pole of the spleen and cardiophrenic lymph nodes, consistent with metastasis, was performed. Notably, the Da Vinci SP system's relocation function proved useful in this case, particularly in slender patients with multiple distant metastases. CONCLUSION: This case underscores the importance of technological advancements in robotic surgery. The Da Vinci SP system, with its advantageous features, shows promise in challenging clinical scenarios. Its ability to facilitate precise navigation and manipulation within the patient's restricted abdominal cavity contributed to the observed successful outcome.
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Carcinoma Hepatocelular , Hepatectomia , Neoplasias Hepáticas , Metastasectomia , Recidiva Local de Neoplasia , Procedimentos Cirúrgicos Robóticos , Humanos , Carcinoma Hepatocelular/cirurgia , Carcinoma Hepatocelular/patologia , Carcinoma Hepatocelular/secundário , Feminino , Procedimentos Cirúrgicos Robóticos/métodos , Neoplasias Hepáticas/cirurgia , Neoplasias Hepáticas/secundário , Neoplasias Hepáticas/patologia , Adolescente , Hepatectomia/métodos , Metastasectomia/métodos , Recidiva Local de Neoplasia/cirurgia , Recidiva Local de Neoplasia/patologia , Prognóstico , Neoplasias Peritoneais/secundário , Neoplasias Peritoneais/cirurgia , Metástase LinfáticaRESUMO
Fibrolamellar carcinoma is a rare liver tumor, with most cases arising in people younger than 40 years of age. We present a case series of five patients with histological confirmation of fibrolamellar carcinoma who had liver resection as the primary treatment. The median age of diagnosis was 24 years with nonspecific clinical manifestations in otherwise healthy patients. Alpha-fetoprotein levels were widely variable. Patients had classical imaging, macroscopic, and microscopic findings. Most of our patients underwent a hemihepatectomy and 60% recurred after the first year.
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PURPOSE: Hepatocellular carcinoma (HCC), the second most common pediatric malignant liver tumor after hepatoblastoma, represents 1% of all pediatric tumors. METHODS: A retrospective study was conducted on children with HCC treated at our center from March 2002 to October 2022, excluding those with inadequate follow-up or records. Demographic data, initial complaints, alpha-fetoprotein (AFP) values, underlying disease, size and histopathological features of the masses, chemotherapy, and long-term outcomes were analyzed. RESULTS: Fifteen patients (8 boys, 7 girls) with a mean age of 11.4 ± 4.1 years (0.8-16.4 years) were analyzed. The majority presented with abdominal pain, with a median AFP of 3.9 ng/mL. Hepatitis B cirrhosis in one patient (6.6%) and metabolic disease (tyrosinemia type 1) in two patients (13.3%) were the underlying diseases. Histopathological diagnoses were fibrolamellar HCC (n:8; 53.3%), HCC (n:6; 40%). Four of the 15 patients underwent liver transplantation, and 9 underwent surgical resection. Due to late diagnosis, two patients were considered inoperable (13.3%). The survival rate for the four patients who underwent liver transplantation was found to be 75%. CONCLUSION: Surgical treatment of various variants of HCC can be safely performed in experienced centers with a multidisciplinary approach, and outcomes are better than in adults.
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Carcinoma Hepatocelular , Neoplasias Hepáticas , Transplante de Fígado , Humanos , Masculino , Neoplasias Hepáticas/cirurgia , Carcinoma Hepatocelular/cirurgia , Feminino , Estudos Retrospectivos , Criança , Adolescente , Pré-Escolar , Lactente , Resultado do Tratamento , Hepatectomia/métodos , Taxa de Sobrevida , SeguimentosRESUMO
An 11-year-old boy presented with vomiting and abdominal pain. Ultrasonography and blood tests revealed no abnormalities. He was diagnosed with viral gastroenteritis; however, the following morning, he was found dead in bed. Postmortem examination revealed that a 1,900 mL hemorrhage with strong coagulation from the diaphragm was the cause of death. He had no traumatic episodes, injuries, or a medical history of hemorrhagic diathesis. The presence of a fibrin-like clot indicated coagulation activation; however, most criteria for disseminated intravascular coagulation were not observed. Fibrolamellar carcinoma, a rare hepatocellular carcinoma, was found; however, liver disorder was not estimated based on the pathological findings. In conclusion, the mechanism of hemorrhage could not be explained. Although we were unable to identify the cause of the hemorrhage, we could not completely rule out the possibility that fibrolamellar carcinoma had an unknown influence on the hemorrhage. Given the limited number of studies on fibrolamellar carcinoma, we present a case of a boy with undiagnosed fibrolamellar carcinoma who died due to severe hemorrhage.
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Fibrolamellar hepatocellular carcinoma (FLHCC) is a rare and distinct subtype of liver cancer, predominantly affecting younger patients without underlying liver diseases. This case report discusses a unique presentation of FLHCC in a 38-year-old male with a past medical history of a well-controlled seizure disorder. The patient presented with nausea, vomiting, and abdominal pain following a fatty meal. Laboratory tests revealed elevated liver enzymes and anemia, and imaging showed a large hepatic lesion. Initial management included a septic workup and broad-spectrum antibiotics. However, a liver biopsy performed subsequently revealed the presence of FLHCC. The patient underwent a successful open right hepatectomy and was managed postoperatively with consideration of his seizure disorder. Follow-up at six months showed a stable postoperative condition without any evidence of recurrence. The diagnosis of FLHCC is challenging due to its rarity and nonspecific presentation. The case emphasizes the importance of considering FLHCC in the differential diagnosis of hepatic lesions, particularly in young patients. Surgical resection remains the primary treatment modality. This case underscores the importance of a thorough evaluation of hepatic lesions, especially in younger patients. It also illustrates the complexities in managing patients with FLHCC, requiring a multidisciplinary approach for optimal outcomes. Further research is necessary to better understand the pathogenesis of FLHCC and to develop more effective treatment strategies.
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Fibrolamellar carcinoma (FLC) is a liver tumor with a high mortality burden and few treatment options. A promising therapeutic vulnerability in FLC is its driver mutation, a conserved DNAJB1-PRKACA gene fusion that could be an ideal target neoantigen for immunotherapy. In this study, we aim to define endogenous CD8 T cell responses to this fusion in FLC patients and evaluate fusion-specific T cell receptors (TCRs) for use in cellular immunotherapies. We observe that fusion-specific CD8 T cells are rare and that FLC patient TCR repertoires lack large clusters of related TCR sequences characteristic of potent antigen-specific responses, potentially explaining why endogenous immune responses are insufficient to clear FLC tumors. Nevertheless, we define two functional fusion-specific TCRs, one of which has strong anti-tumor activity in vivo. Together, our results provide insights into the fragmented nature of neoantigen-specific repertoires in humans and indicate routes for clinical development of successful immunotherapies for FLC.
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Carcinoma Hepatocelular , Humanos , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/terapia , Carcinoma Hepatocelular/patologia , Receptores de Antígenos de Linfócitos T/genética , Linfócitos T/patologia , Terapia Baseada em Transplante de Células e Tecidos , Proteínas de Choque Térmico HSP40/genética , Subunidades Catalíticas da Proteína Quinase Dependente de AMP Cíclico/genéticaRESUMO
Aim The aim of this study is to define genomic variations between fibrolamellar hepatocellular carcinoma (FL-HCC) and conventional hepatocellular carcinoma (HCC) Methods This study used the American Association for Cancer Research (AACR) Project GENIE data as a foundational element. Specifically, information about both fibrolamellar and conventional hepatocellular carcinoma was retrieved from this database. Results A total of 719 patients diagnosed with HCC and 52 individuals presenting with FL-HCC underwent thorough analysis. Notably, distinct variances in gene alterations were observed between the two cohorts. Predominantly, the HCC group exhibited frequent occurrences of mutations within the TP53 and CTNNB1 genes. Conversely, DNAJB1 fusion was uniquely identified in FL-HCC cases. Conclusion This study significantly broadens our understanding of the genetic makeup associated with FL-HCC and HCC. It is particularly notable because it reveals clear disparities in gene modifications between FL-HCC and HCC. Further investigation is essential to unravel the functional consequences of these genetic variances. This exploration will aid in the development of targeted therapeutic approaches to enhance the prognosis of patients diagnosed with diverse subtypes of HCC.
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Purpose: Fibrolamellar hepatocellular carcinoma (FLHCC) is a rare primary liver malignancy often diagnosed at advanced stages. While there are limited data on the efficacy of specific agents, we aim to report outcomes of patients treated with systemic therapies and explore prognostic factors. Patients and Methods: Medical records of patients treated between 2010 and 2022 were reviewed. Treatments were defined after multidisciplinary assessment. Descriptive statistics were used for baseline demographics. Time-to-event outcomes were estimated using the Kaplan-Meier method, compared by log-rank and adjusted by a regression model. Radiomic features (including size, shape, and texture) of the primary lesion were extracted and dimensionality reduced. An unsupervised Gaussian Mixture Model (GMM) clustering was performed, and survival was compared between clusters. Results: We identified 23 patients: 12 males, with a median age of 23.6 years. At diagnosis, 82.6% had metastases, most frequently to the lungs (39.1%), lymph nodes (39.1%), and peritoneum (21.7%). Patients received a median of three lines (1-8) of treatment, including different regimens. Sorafenib (39.1%), capecitabine (30.4%), and capecitabine/interferon (13%) were the most used first-line regimens. The median time-to-failure was 3.8 months (95% CI: 3.2-8.7). Capecitabine + interferon (42.1%) and platinum combinations (39.1%) were the most used second-line regimens, with a time-to-failure of 3.5 months (95% CI: 1.5-11.6). Median overall survival was 26.7 months (95% CI: 15.1-40.4). A high baseline neutrophil-to-lymphocyte ratio (NLR) was associated with worse survival (p=0.02). Radiomic features identified three clusters, with one cluster (n=6) having better survival (40.4 vs 22.6 months, p=0.039). Tumor sphericity in the arterial phase was the most relevant characteristic associated with a better prognosis (accuracy=0.93). Conclusion: FLHCC has unique features compared to conventional HCC, including young onset, gender balance, and absence of hepatopathy. Systemic therapies can provide encouraging survival, but lack of uniformity precludes defining a preferable regimen. Radiomics and NLR were suggested to correlate with prognosis and warrant further validation.
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BACKGROUND: Fibrolamellar hepatocellular carcinoma (HCC) (FL-HCC) is rare in Japan. FL-HCC develops in young patients with no history of cirrhosis and tends to manifest lymphatic metastasis with clinical features similar to those of HCC. We present a case of FL-HCC in a young male patient. CASE PRESENTATION: A 14-year-old male patient underwent abdominal computed tomography (CT) to diagnose appendicitis, wherein a hepatic tumor was detected. Dynamic enhanced CT revealed a 35-mm solid tumor, which contrasted at the early phase of dynamic enhanced study of the right hepatic segments, with occlusion of the right portal vein. We performed right hepatectomy for these lesions. The patient experienced a single lymphatic recurrence on the hepatoduodenal ligament 12 months after the initial surgery. We performed lymphadenectomy for the recurrent tumor. We performed RNA sequencing (RNA-seq) and targeted DNA sequencing of the resected specimens (primary tumor, lymphatic metastasis, and normal liver). RNA-seq detected DNAJB1-PRKACA in both primary and metastatic lesions as previously reported. Furthermore, The Cancer Genome Atlas (TCGA) database was used to compare other gene expressions in this case with those of previously reported cases of FL-HCC and HCC in young patients. Principal component analysis of differentially expressed genes in the top 10% revealed that the gene expression in our case was similar to that of previous FL-HCC cases but was a different cluster from that in HCC cases in young patients. Mutational analysis did not detect any somatic mutations associated with carcinogenesis, including previously reported mutations (Kastenhuber et al. in Proc Natl Acad Sci USA 114: 13076-84, 2017). CONCLUSION: We encountered a case of FL-HCC, a rare hepatic tumor in an adolescent patient, and evaluated the genetic background. Our findings could contribute to the elucidation of the mechanisms underlying carcinogenesis and progression in patients with FL-HCC and thereby contribute to the development of new therapeutic strategies in the future that may improve patient prognosis.
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BACKGROUND: Fibrolamellar carcinoma (FLC) is a rare type of liver cancer that primarily affects adolescents and young adults without prior liver disease or viral infections. Patients with FLC generally have non-specific symptoms, are often diagnosed at a later stage, and experience a higher frequency of metastases compared to patients with other liver cancers. A fusion transcript of DNAJB1 and PRKACA, which can lead to increased activity of PKA and cellular proliferation, has been identified in all FLC patients, but the exact mechanism through which FLC develops remains unclear. In this study, we investigated common lncRNA profiles in various FLC samples using bioinformatics analyses. METHODS: We analyzed differentially expressed (DE) lncRNAs from three RNA sequencing datasets. Using lncRNAs and DE mRNAs, we predicted potential lncRNA target genes and performed Gene Ontology (GO) and KEGG analyses with the DE lncRNA target genes. Moreover, we screened for small-molecule compounds that could act as therapeutic targets for FLC. RESULTS: We identified 308 DE lncRNAs from the RNA sequencing datasets. In addition, we performed a trans-target prediction analysis and identified 454 co-expressed pairs in FLC. The GO analysis showed that the lncRNA-related up-regulated mRNAs were enriched in the regulation of protein kinase C signaling and cAMP catabolic processes, while lncRNA-related down-regulated mRNAs were enriched in steroid, retinol, cholesterol, and xenobiotic metabolic processes. The analysis of small-molecule compounds for FLC treatment identified vitexin, chlorthalidone, triamterene, and amiloride, among other compounds. CONCLUSIONS: We identified potential therapeutic targets for FLC, including lncRNA target genes as well as small-molecule compounds that could potentially be used as treatments. Our findings could contribute to furthering our understanding of FLC and providing potential avenues for diagnosis and treatment.
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Carcinoma Hepatocelular , Neoplasias Hepáticas , RNA Longo não Codificante , Adolescente , Adulto Jovem , Humanos , RNA Longo não Codificante/genética , Sequência de Bases , Carcinoma Hepatocelular/tratamento farmacológico , Carcinoma Hepatocelular/genética , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/genética , RNA Mensageiro/genética , Proteínas de Choque Térmico HSP40RESUMO
BACKGROUND/AIM: Fibrolamellar hepatocellular carcinoma (FLHCC) is a rare tumor presenting in younger patients without chronic liver disease. Up to 80-100% develop recurrent disease, necessitating additional surgery or systemic treatment. Systemic options and pre-clinical treatment studies are lacking. We previously described patient-derived xenograft (PDX) development, allowing for pre-clinical studies. Herein, we develop FLHCC PDX models and utilize these to define tumor characteristics and determine the efficacy of systemic agents. MATERIALS AND METHODS: Primary and lymph node metastatic tumor tissues were obtained at the time of FLHCC resection in two patients. Tumor lysates were screened for protein upregulation. Cell lines were generated from metastatic and primary tumor tissue. The viability of the cell lines was assessed after treatment with temsirolimus, gemcitabine/oxaliplatin, and FOLFIRINOX. Two PDX models were developed from metastatic tissue. For in vivo studies, tumor-bearing mice were treated with temsirolimus, FOLFIRINOX, and Gemcitabine/oxaliplatin. RESULTS: PDX models were successfully generated from metastatic FLHCC, which closely recapitulated the original tumor. Upregulation of mTOR was seen in metastatic tissue compared to primary tumors. Cell lines from metastatic tissue demonstrated significant sensitivity to temsirolimus. In vivo testing of PDX models demonstrated a significant response to single-agent temsirolimus with minimal toxicity. CONCLUSION: Herein, we demonstrate the feasibility of developing PDX models that closely recapitulate FLHCC. Upregulation of mTOR was seen in metastatic tissue compared to primary tissue. The efficacy of mTOR inhibition with temsirolimus treatment suggests that the upregulation of the mTOR pathway may be a significant mechanism for growth in metastatic lesions and a potential target for therapeutics.
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Carcinoma Hepatocelular , Neoplasias Hepáticas , Neoplasias Pancreáticas , Humanos , Animais , Camundongos , Carcinoma Hepatocelular/tratamento farmacológico , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/metabolismo , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Hepáticas/patologia , Oxaliplatina , Serina-Treonina Quinases TOR/metabolismoRESUMO
Fibrolamellar carcinomas (FLCs), lethal tumors occurring in children to young adults, have genetic signatures implicating derivation from biliary tree stem cell (BTSC) subpopulations, co-hepato/pancreatic stem cells, involved in hepatic and pancreatic regeneration. FLCs and BTSCs express pluripotency genes, endodermal transcription factors, and stem cell surface, cytoplasmic and proliferation biomarkers. The FLC-PDX model, FLC-TD-2010, is driven ex vivo to express pancreatic acinar traits, hypothesized responsible for this model's propensity for enzymatic degradation of cultures. A stable ex vivo model of FLC-TD-2010 was achieved using organoids in serum-free Kubota's Medium (KM) supplemented with 0.1% hyaluronans (KM/HA). Heparins (10 ng/ml) caused slow expansion of organoids with doubling times of â¼7-9 days. Spheroids, organoids depleted of mesenchymal cells, survived indefinitely in KM/HA in a state of growth arrest for more than 2 months. Expansion was restored with FLCs co-cultured with mesenchymal cell precursors in a ratio of 3:7, implicating paracrine signaling. Signals identified included FGFs, VEGFs, EGFs, Wnts, and others, produced by associated stellate and endothelial cell precursors. Fifty-three, unique heparan sulfate (HS) oligosaccharides were synthesized, assessed for formation of high affinity complexes with paracrine signals, and each complex screened for biological activity(ies) on organoids. Ten distinct HS-oligosaccharides, all 10-12 mers or larger, and in specific paracrine signal complexes elicited particular biological responses. Of note, complexes of paracrine signals and 3-O sulfated HS-oligosaccharides elicited slowed growth, and with Wnt3a, elicited growth arrest of organoids for months. If future efforts are used to prepare HS-oligosaccharides resistant to breakdown in vivo, then [paracrine signal-HS-oligosaccharide] complexes are potential therapeutic agents for clinical treatments of FLCs, an exciting prospect for a deadly disease.
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Carcinoma , Sulfatos , Criança , Humanos , Comunicação Parácrina , Heparitina Sulfato/metabolismo , Oligossacarídeos/farmacologia , Oligossacarídeos/metabolismoRESUMO
"Rauisuchia" is a non-monophyletic group of quadrupedal and carnivorous pseudosuchians that inhabited the entire world during the Middle-Upper Triassic period (Anisian/Ladinian-Rhaetian). In South America, "rauisuchians" reached the largest sizes among continental carnivores. Despite their important ecological role, some aspects of their palaeobiology have been poorly examined. Here, we study appendicular bones, dorsal ribs and osteoderms of two genera, the Argentinean Fasolasuchus tenax (PVL 3850, holotype) and the Brazilian Prestosuchus chiniquensis (SNSB-BSPG AS XXV) respectively. The femur of F. tenax is formed by laminar fibrolamellar bone, which is composed of non-fully monorefringent woven-fibred matrix and primary osteons; the dorsal rib has a Haversian bone composition with an external fundamental system recorded and the osteoderm is formed by well-organised parallel-fibred bone. The femur, humerus and fibula of P. chiniquensis are mostly composed of strongly arranged parallel-fibred bone and a laminar vascularisation. The minimal ages obtained correspond to 9 years for F. tenax (based on the maximum number of growth marks in the osteoderm) and 4 years for P. chiniquensis (obtained from the highest count of growth marks in the femur and in the humerus). F. tenax attained somatic and skeletal maturity, while P. chiniquensis was near to reaching skeletal and sexual maturity, but it was somatically immature. The overall rapid growth rate and the high and uniform vascularisation seems to imply that these features are common in most of "rauisuchians", except in P. chiniquensis.
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Fêmur , Costelas , Brasil , Argentina , Colorado , Fêmur/anatomia & histologia , FósseisRESUMO
BACKGROUND: The prognosis of fibrolamellar carcinoma (FLC) versus conventional hepatocellular carcinoma (HCC) remains controversial. Thus, this study aimed to compare the prognosis of FLC and HCC. METHODS: Patients with FLC and HCC in the Surveillance, Epidemiology, and End Results (SEER) database between 2000 and 2015 were included. Propensity score matching (PSM) was performed to balance the clinical characteristics between FLC and HCC. Cox regression and Kaplan-Meier analysis were applied to identify the effect of pathology in prognosis before and after match in the whole cohort, as well as in subgroups of fibrosis score, AJCC stage and therapy. RESULTS: A total of 213 patients with FLC and 33365 patients with HCC between 2000 and 2015 were identified. Before matching, the overall survival (OS) and cancer-specific survival (CSS) were significantly better in FLC than HCC. After matching, FLC patients had better OS than HCC patients, but the CSS was similar between groups. Further analyses found that in patients at early stage (AJCC I-III) and/or accepted curative therapy, the prognosis was comparable between HCC and FLC. In patients without cirrhosis (F0), the HCC patients had similar prognosis with FLC patients. Prognosis benefit of FLC was observed in subgroups of AJCC stage IV and non-curative therapy, however, the concomitant diseases may affect the results. CONCLUSIONS: The prognosis of FLC was significantly better than HCC before matching. However, after matching for clinical characteristics, the CSS was comparable between FLC and HCC.
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Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Pontuação de Propensão , Prognóstico , Estudos RetrospectivosRESUMO
Fibrolamellar carcinoma (FLC) of the liver is a rare type of liver cancer that is prevalent in children and young adults, often less than 40 years old. The etiology is unclear. It presents without underlying liver disease with distinctive histological features such as fibrous collagen bands surrounding the tumor cells. Fusion protein DNAJB1-PRKACA is found in most of the cases. The prognosis of FLC is poor. Even though curative treatment option is surgery for a certain patient population, other treatment modalities including radiation, chemotherapy are currently being used without significant improvement of overall survival. Recently, targeted therapy and immunotherapy have been studied which may provide survival advantage in the future. This review sought to compile data from clinical trials and case reports/series to outline the current state of FLC treatment.
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Objective: Indolent T-lymphoblastic proliferation (iT-LBP) is a non-neoplastic disease with an indolent clinical course, manifesting as hyperplasia of immature extrathymic T-lymphoblastic cells. Isolated iT-LBP has been observed, but the majority of iT-LBP cases has been seen in conjunction with other diseases. iT-LBP is easily misdiagnosed as T-lymphoblastic lymphoma/leukemia, and understanding the disease of indolent T-lymphoblastic proliferation may prevent misdiagnosis and missed diagnosis in pathological diagnosis. Case presentation: We report a case morphology, immunophenotypic, and molecular features of iT-LBP combined with fibrolamellar hepatocellular carcinoma developed after colorectal adenocarcinoma and review relevant literature. Conclusion: iT-LBP combined with fibrolamellar hepatocellular carcinoma developed after colorectal adenocarcinoma is relatively rare and should always be considered as a differential diagnosis of T-lymphoblastic lymphoma and scirrhous hepatocellular carcinoma as the two disorders show highly similar clinical features.
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Adenocarcinoma , Carcinoma Hepatocelular , Neoplasias Colorretais , Neoplasias Hepáticas , Lesões Pré-Cancerosas , Leucemia-Linfoma Linfoblástico de Células T Precursoras , Humanos , Carcinoma Hepatocelular/patologia , Hiperplasia , Neoplasias Hepáticas/patologia , Leucemia-Linfoma Linfoblástico de Células T Precursoras/diagnóstico , Leucemia-Linfoma Linfoblástico de Células T Precursoras/patologia , Proliferação de CélulasRESUMO
Fibrolamellar hepatocellular carcinoma is a rare primary hepatic tumor that usually occurs in youth. The common presenting features are vague abdominal pain, nausea, vomiting and weight loss. We present a case report of a young male who presented with cholestatic jaundice and on evaluation was diagnosed to have fibrolamellar hepatocellular carcinoma. He underwent successful surgical resection of the tumor. In young individuals presenting with unexplained cholestasis, fibrolamellar hepatocellular carcinoma should be considered.
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Carcinoma Hepatocelular , Icterícia Obstrutiva , Neoplasias Hepáticas , Adolescente , Humanos , Masculino , Carcinoma Hepatocelular/complicações , Carcinoma Hepatocelular/diagnóstico , Carcinoma Hepatocelular/patologia , Neoplasias Hepáticas/complicações , Neoplasias Hepáticas/diagnóstico , Neoplasias Hepáticas/patologia , Icterícia Obstrutiva/diagnóstico , Icterícia Obstrutiva/etiologia , Doenças RarasRESUMO
Hyperammonemic encephalopathy is a potentially fatal condition associated with fibrolamellar hepatocellular carcinoma. The mechanism involved in hyperammonemia in patients with fibrolamellar carcinoma was unclear until a possible physiopathological pathway was recently proposed. An ornithine transcarboxylase dysfunction was suggested as a result of increased ornithine decarboxylase activity induced by c-Myc overexpression. This c-Myc overexpression resulted from Aurora kinase A overexpression derived from the activity of a chimeric kinase that is the final transcript of a deletion in chromosome 19, common to all fibrolamellar carcinomas. We performed the analysis of the expression of all enzymes involved and tested for the mutation in chromosome 19 in fresh frozen samples of fibrolamellar hepatocellular carcinoma, non-tumor liver, and hepatic adenomatosis. The specific DNAJB-PRKACA fusion protein that results from the recurrent mutation on chromosome 19 common to all fibrolamellar carcinoma was detected only in the fibrolamellar carcinoma sample. Fibrolamellar carcinoma and adenomyomatosis samples presented increased expression of Aurora kinase A, c-MYC, and ornithine decarboxylase when compared to normal liver, while ornithine transcarbamylase was decreased. The proposed physiopathological pathway is correct and that overexpression of c-Myc may also be responsible for hyperammonemia in patients with other types of rapidly growing hepatomas. This gives further evidence to apply new and adequate treatment to this severe complication.