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BACKGROUND AND AIMS: Assessment of recurrence risk after liver resection (LR) is critical in hepatocellular carcinoma (HCC), particularly with the advent of effective adjuvant therapy. The aim of the study was to analyze the clinical and pathological factors associated with recurrence, aggressive recurrence, and survival after LR. METHOD: Retrospective study in which all single HCC (BCLC-0/A) patients treated with LR between February 2000 and November 2020 were included. The main clinical variables were recorded. Histological features were blindly evaluated by two independent pathologists. Aggressive recurrence was defined as those that exceeded the Milan criteria at 1st recurrence. RESULTS: A total of 218 patients were included (30% BCLC 0 and 70% BCLC A), median (IQR) tumor size of 28 (19-42mm). The prevalence of microvascular invasion and/or satellitosis (mVI/S) was 39%, with a kappa-index between both pathologists of 0.8. After a median follow-up of 49 (23-85) months, 61/218 (28%) patients died, 32/218 (15%) underwent LT, 127 (58%) developed HCC recurrence. The prevalence of aggressive recurrence was 35% (44/127 Milan-out, with 20 cases at advanced stage), and the 5-year survival was 81%. The presence of mVI/S was the only independent predictor of recurrence [HR:1.83 (1.28-2.61), p<0.001], aggressive recurrence [HR:3.31(1.74-6.29), p<0.001] and mortality [HR:2.23(1.27- 3.91), p:0.005]. The presence of MTM was significantly associated with a higher prevalence of mVI/S, Edmonson Steiner grade III-IV, AFP values and vessels that encapsulate tumor clusters, but MTM was not significantly associated with recurrence, aggressive recurrence, or OS. CONCLUSION: The presence of mVI/S was the only independent risk factor for aggressive recurrence and mortality. This has important implications for early-stage patient management, especially in the setting of adjuvant immunotherapy or ab initio LT.
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BACKGROUND & AIMS: Recognition of non-characterized liver nodules (NCLN) prior to direct-acting antivirals (DAAs) is associated with increased hepatocellular carcinoma (HCC) risk in patients with HCV. The risk of HCC has not been defined in F3/F4 patients in whom NCLN have been ruled-out before starting DAAs and at sustained virological response (SVR). This study aimed to estimate HCC incidence in this population. METHODS: We performed a prospective study including HCV-infected patients with F3/F4 fibrosis, without a history of HCC, and who achieved SVR after DAAs. Patients were only included if they had undergone ultrasound imaging that excluded the presence of HCC/NCLN within 30 days after SVR. All patients were evaluated every 6 months until developing primary liver cancer, death or withdrawal of informed consent. HCC incidence was expressed per 100 patient-years (/100PY). Adherence to screening program was calculated every 6 months for the first 48 months. RESULTS: A total of 185 patients (63/122, F3/F4) were included. Among those with cirrhosis, 92% were Child-Pugh A and 42.7% had clinically significant portal hypertension (CSPH). Albumin-bilirubin score was 1 in 84.9% and 2 in 15.1% of patients, respectively. The median clinical and radiologic follow-up was 52.4 months and 48 months, respectively. Ten patients developed HCC: HCC incidence was 1.46/100PY (95% CI 0.79-2.71) in the whole cohort, 2.24/100PY (95% CI 1.21-4.17) in F4 only and 3.63/100PY (95% CI 1.95-6.74) in patients with CSPH. No HCC was registered in patients with F3. Median time between SVR and HCC occurrence was 28.1 months; 12 non-primary liver cancers were also identified. CONCLUSIONS: Patients with cirrhosis without NCLN at SVR remain at risk of HCC development. The absence of HCC in patients with F3 reinforces their marginal cancer risk, but prospective studies are needed to exclude them from screening programs. LAY SUMMARY: Patients with HCV-related cirrhosis, without non-characterized liver nodules at sustained virologic response, remain at risk of hepatocellular carcinoma despite viral cure. However, the cancer risk after successful direct-acting antiviral treatment is marginal in patients with F3 fibrosis without non-characterized liver nodules. If confirmed in larger prospective studies, current screening recommendations may need to be revisited in this group of patients.
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Carcinoma Hepatocelular , Hepatite C Crônica , Hipertensão Portal , Neoplasias Hepáticas , Antivirais/uso terapêutico , Carcinoma Hepatocelular/tratamento farmacológico , Carcinoma Hepatocelular/epidemiologia , Carcinoma Hepatocelular/etiologia , Hepatite C Crônica/complicações , Hepatite C Crônica/tratamento farmacológico , Humanos , Hipertensão Portal/complicações , Cirrose Hepática/complicações , Cirrose Hepática/tratamento farmacológico , Cirrose Hepática/epidemiologia , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/epidemiologia , Neoplasias Hepáticas/etiologia , Estudos Prospectivos , Resposta Viral SustentadaRESUMO
The aims of the study were to investigate and compare the immunophenotype of tumor-infiltrating lymphocytes (TILs) and PD-L1 expression in a series of benign, intermediate and malignant Spitzoid lesions showing marked inflammatory lymphoid component, to find out its possible relation with the prognosis of these lesions. Six out of 97 Spitz nevus (SN) (6 %), five out of 26 atypical Spitz tumors (AST) (16 %) and seven out of 37 Spitzoid melanomas (SM) (19 %) showed diffuse, intense inflammatory component and were included in the study. The biological risk of the tumors was assessed in all AST through the melanoma 4 probe-FISH assay and the 9p21 locus exploration. TILs were quantitatively immunophenotyped using CD3, CD4, CD8, CD20, TIA1, FOXP3 and PD1 antibodies. PD-L1 was assessed in tumoral cells and inflammatory cells adjacent to the tumor. No significant differences of TILs immunophenotype were found between SN, AST and SM. However, the classification of tumors according to the biological risk showed that grouped SN plus low-risk AST had a significantly higher number of T-cells CD8+ and TIA-1+, as well as a lower CD4/CD8 relation and B- lymphocyte number than high-risk of progression tumors (grouped high-risk AST plus SM). Immunoregulatory T-cell markers PD1 and FOXP3 only correlated with each other and with PD-L1 expression. In conclusion, The TILs immunoprofile differences between low-risk and high-risk of progression Spitzoid tumors, especially regarding CD8 and the cytotoxic immune response, can add prognostic information about these challenging tumors and impact the clinical management of patients.
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Melanoma , Nevo de Células Epitelioides e Fusiformes , Neoplasias Cutâneas , Antígeno B7-H1/metabolismo , Fatores de Transcrição Forkhead/metabolismo , Humanos , Linfócitos do Interstício Tumoral/patologia , Melanoma/patologia , Nevo de Células Epitelioides e Fusiformes/patologia , Prognóstico , Neoplasias Cutâneas/patologiaAssuntos
Anticorpos Monoclonais Humanizados , Antineoplásicos Imunológicos , Doença Hepática Induzida por Substâncias e Drogas , Humanos , Anticorpos Monoclonais Humanizados/efeitos adversos , Doença Hepática Induzida por Substâncias e Drogas/etiologia , Doença Hepática Induzida por Substâncias e Drogas/imunologia , Doença Hepática Induzida por Substâncias e Drogas/diagnóstico , Antineoplásicos Imunológicos/efeitos adversos , Masculino , Melanoma/tratamento farmacológico , Melanoma/imunologia , Feminino , Inibidores de Checkpoint Imunológico/efeitos adversos , Fígado/patologia , Fígado/efeitos dos fármacos , Fígado/imunologia , Pessoa de Meia-Idade , IdosoRESUMO
Biliary tract cancers (BTCs) are rare and aggressive malignancies with an increasing incidence and poor prognosis. The standard systemic treatment for BTCs has evolved to include immune checkpoint inhibitors associated with gemcitabine-cisplatin as first-line therapies. However, survival rates remain low, highlighting the critical need for personalized treatment strategies based on molecular profiling. Currently, significant advancements have been made in the molecular characterization of BTCs, where genetic alterations, such as IDH1 mutations and FGFR2 fusions, provide targets for therapy. Molecular profiling is crucial early in the management process to identify potential candidates for clinical trials and guide treatment strategy. The integration of these molecular insights into clinical practice has allowed for the development of targeted therapies, although many of them are still in the phase 2 trial stage without definitive survival benefits demonstrated in phase 3 trials. This integration of comprehensive molecular profile insights with traditional treatment approaches offers a new horizon in the personalized medicine landscape for BTCs, with the aim of significantly improving patient outcomes through precision oncology.
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Neoplasias do Sistema Biliar , Medicina de Precisão , Humanos , Neoplasias do Sistema Biliar/tratamento farmacológico , Neoplasias do Sistema Biliar/genética , Neoplasias do Sistema Biliar/terapia , Medicina de Precisão/métodos , Terapia de Alvo Molecular/métodosRESUMO
BACKGROUND/AIM: Dermatological adverse events (DAE) in hepatocellular carcinoma (HCC) patients treated with sorafenib predicts better outcome. Some turn into skin lesions (SL) requiring pathology examination. We describe incidence, characteristics and molecular profile of SL in HCC patients treated with sorafenib. MATERIALS AND METHODS: SL were prospectively collected in 311 HCC patients who started sorafenib. SL from sorafenib cohort were compared to those from a control patient group selected to match SL type and demographics. HRAS, KRAS and BRAF mutations were analyzed by CAST-PCR, mutated p53 and MAPK pathway activation by immunohistochemistry and immune infiltration by hematoxylin-eosin staining. RESULTS: Eighty-eight out of 311 patients developed DAE and 7.4% SL required histological assessment. Most frequent lesions were keratoacanthomas (n = 4), squamous-cell carcinomas (SCC)(n = 5), basal-cell carcinomas (BCC)(n = 3) and seborrheic keratosis (n = 5). HRAS and KRAS mutations were detected in 4 SL, while no mutations showed in control SL. Nuclear pERK immunostaining was identified in 33.3% of cases versus 5.3% of controls. Most SL (90%) from patients with DAE were proliferative with intense immune infiltration (73%). CONCLUSIONS: The onset of SL and their molecular profile did not impact negatively on patient's prognosis, but intense proliferation of SL may reflect compensatory activation of MAPK pathway and warrants their close monitoring.