Browsing by Author "Cano, L"

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A preoperative nomogram for predicting long-term survival after resection of large hepatocellular carcinoma (>10 cm)
(Elsevier B.V., 2022) Ruiz-Figueroa, E; Pineau, P; Flores, C; Fernández, R; Cano, L; Cerapio, JP; Casavilca-Zambrano, S; Berrospi, F; Chávez, I; Roche, B; Bertani, S
Background: It has previously been demonstrated that a fraction of patients with hepatocellular carcinoma (HCC) > 10 cm can benefit from liver resection. However, there is still a lack of effective decision-making tools to inform intervention in these patients. Methods: We analysed a comprehensive set of clinical data from 234 patients who underwent liver resection for HCC >10 cm at the National Cancer Institute of Peru between 1990 and 2015, monitored their survival, and constructed a nomogram to predict the surgical outcome based on preoperative variables. Results: We identified cirrhosis, multifocality, macroscopic vascular invasion, and spontaneous tumour rupture as independent predictors of survival and integrated them into a nomogram model. The nomogram's ability to forecast survival at 1, 3, and 5 years was subsequently confirmed with high concordance using an internal validation. Through applying this nomogram, we stratified three groups of patients with different survival probabilities. Conclusion: We constructed a preoperative nomogram to predict long-term survival in patients with HCC >10 cm. This nomogram is useful in determining whether a patient with large HCC might truly benefit from liver resection, which is paramount in low- and middle-income countries where HCC is often diagnosed at advanced stages. © 2021 The Author(s)
Early-onset liver cancer in South America associates with low hepatitis B virus DNA burden
(Nature Publishing Group, 2018) Marchio, A; Cerapio, JP; Ruiz, E; Cano, L; Casavilca-Sambrano, S; Terris, B; Deharo, E; Dejean, A; Bertani, S; Pineau, P
In Peru, hepatocellular carcinoma (HCC) arises in young non-cirrhotic patients. Hepatitis B virus (HBV) is suspected to be the prominent etiological agent. We thus performed a comprehensive molecular study of HBV infection in 65 Peruvian HCC patients. Only 51% were considered as persistently infected at the onset. HBV DNA was found by PCR in the tumor and/or matched non-tumor liver tissues in more than 80% of cases (n = 53/65). HBV DNA was significantly more abundant in livers of younger patients than in those of the older ones. We consistently observed low viral DNA burden (0.1-6.5 copies for 100 cells), with viral genomes in younger patients displaying higher proportion of mutations at di-pyrimidines (TpT and CpC, P = 0.006). A drastic activation of multiple DNA repair pathways in tumors of younger patients was observed. Our observations clearly challenge the current vision that associates high HBV DNA load with earlier tumor development. We concluded that in Peru, and maybe in other populations with Americas' indigenous ancestry, HBV-associated liver tumorigenesis might differ significantly from that generally observed in the rest of the world. Procedures used to screen for HCC development in subjects at risk should be adapted to the local situation.
Global DNA hypermethylation pattern and unique gene expression signature in liver cancer from patients with Indigenous American ancestry
(Impact Journals LLC, 2021) Cerapio, JP; Marchio, A; Cano, L; López, I; Fournié, JJ; Régnault, B; Casavilca-Zambrano, S; Ruiz, E; Dejean, A; Bertani, S; Pineau, P
Hepatocellular carcinoma (HCC) usually afflicts individuals in their maturity after a protracted liver disease. Contrasting with this pattern, the age structure of HCC in Andean people displays a bimodal distribution with half of the patients developing HCC in adolescence and early adulthood. To deepen our understanding of the molecular determinants of the disease in this population, we conducted an integrative analysis of gene expression and DNA methylation in HCC developed by 74 Peruvian patients, including 39 adolescents and young adults. While genome-wide hypomethylation is considered as a paradigm in human HCCs, our analysis revealed that Peruvian tumors are associated with a global DNA hypermethylation. Moreover, pathway enrichment analysis of transcriptome data characterized an original combination of signatures. Peruvian HCC forgoes canonical activations of IGF2, Notch, Ras/MAPK, and TGF-β signals to depend instead on Hippo/YAP1, MYC, and Wnt/β-catenin pathways. These signatures delineate a homogeneous subtype of liver tumors at the interface of the proliferative and non-proliferative classes of HCCs. Remarkably, the development of this HCC subtype occurs in patients with one of the four Native American mitochondrial haplogroups A-D. Finally, integrative characterization revealed that Peruvian HCC is apparently controlled by the PRC2 complex that mediates cell reprogramming with massive DNA methylation modulating gene expression and pinpointed retinoid signaling as a potential target for epigenetic therapy.
Hepatocellular carcinoma surgery outcomes in the developing world: A 20-year retrospective cohort study at the National Cancer Institute of Peru
(Elsevier BV, 2016) Ruiz, E; Rojas Rojas, T; Berrospi, F; Chávez, I; Luque, C; Cano, L; Doimi, F; Pineau, P; Deharo, E; Bertani, S
In the developing world, most patients with hepatocellular carcinoma present with advanced-stage disease, considered to be incurable based on current therapeutic algorithms. Here, we demonstrate that curative liver resection is achievable in a portion of Peruvian patients not addressed by these treatment algorithms. We conducted a retrospective cohort study of 253 hepatocellular carcinoma patients that underwent a curative hepatectomy between 1991 and 2011 at the National Cancer Institute of Peru. The median age of the cohort was 36 years, and merely 15.4% of the patients displayed cirrhosis. The average tumor size was over 14 cm in diameter, resulting in 76.3% of major hepatectomies performed. The 5- and 10-year survival probability estimates were 37.5% and 26.2%, respectively. Age (>44 vs. ≤44 years old; P = 0.005), tumor size (>10 cm vs. ≤10 cm in diameter; P = 0.009), cirrhosis (P < 0.001), satellite lesions (P < 0.001), macroscopic vascular invasion (P < 0.001), allogeneic blood transfusion (P = 0.011), and spontaneous rupture of the tumor (P = 0.006) were independent predictive factors for prognosis. Hepatocellular carcinomas in Peru are characterized by a distinct clinical presentation with notable features compared with those typically described throughout relevant literature. Despite a large number of advanced-stage hepatocellular carcinomas, the outcomes of liver resection observed in the present study were in good standing with the results previously described in other series. It thus appears that staging systems and associated therapeutic algorithms designed for use in the developed world remain inadequate in certain populations, especially in the context of Peruvian patients. Our findings suggest that clinicians in the developing world should reconsider management guidelines pertaining to hepatocellular carcinoma. Indeed, we hypothesize that, in developing countries, a strict adherence to these therapeutic algorithms might create a selection bias resulting in the dismissal of patients who could eventually be treated. Keywords: Cancer; Health sciences; Pathobiology of cancer; Treatment of cancer.
Liver clear cell foci and viral infection are associated with non-cirrhotic, non-fibrolamellar hepatocellular carcinoma in young patients from South America
(Nature Publishing Group, 2018) Cano, L; Cerapio, JP; Ruiz, E; Marchio, A; Turlin, B; Casavilca-Sambrano, S; Taxa-Rojas Luis; Marti, G; Deharo, E; Pineau, P; Bertani, S
We previously described a divergent clinical and molecular presentation of hepatocellular carcinoma (HCC) in Peru. The present study aimed to further characterize the tissue features associated with this singular nosological form of HCC in order to gain insight into the natural history of the disease. We performed an exploratory analysis of the histology of both tumor and non-tumor liver (NTL) tissues from 50 Peruvian HCC patients, and compared with that of 75 individuals with non-HCC liver tumor or benign liver lesions as a baseline for NTL features. We complemented this approach with a transcriptome analysis in a subset of NTL tissue samples and also performed an ultra-sensitive hepatitis B virus (HBV) detection in liver tissues of the patients. Overall, results highlighted the low rate of liver parenchymal alterations in a young patient cohort (median age: 40 years old), despite a strong prevalence of underlying HBV infection (c. 67%). Withal, liver clear cell foci of cellular alteration were genuinely associated with HCC and appended to some changes in immune and G protein-coupled receptor gene expression ontologies. Our findings confirm the occurrence of a particular setting of HCC in South America, a region where the pathophysiology of liver cancer remains largely unexplored.