Browsing by Author "Ruiz, E"

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A preoperative risk score based on early recurrence for estimating outcomes after resection of hepatocellular carcinoma in the non-cirrhotic liver
(Elsevier B.V., 2024) Ruiz, E; Honles, J; Fernández, R; Uribe, K; Cerapio, JP; Cancino, K; Contreras-Mancilla, J; Casavilca-Zambrano, S; Berrospi, F; Pineau, P; Bertani, S
Background: Liver resection is the mainstay treatment option for patients with hepatocellular carcinoma in the non-cirrhotic liver (NCL-HCC), but almost half of these patients will experience a recurrence within five years of surgery. Therefore, we aimed to develop a rationale-based risk evaluation tool to assist surgeons in recurrence-related treatment planning for NCL-HCC. Methods: We analyzed single-center data from 263 patients who underwent liver resection for NCL-HCC. Using machine learning modeling, we first determined an optimal cut-off point to discriminate early versus late relapses based on time to recurrence. We then constructed a risk score based on preoperative variables to forecast outcomes according to recurrence-free survival. Results: We computed an optimal cut-off point for early recurrence at 12 months post-surgery. We identified macroscopic vascular invasion, multifocal tumor, and spontaneous tumor rupture as predictor variables of outcomes associated with early recurrence and integrated them into a scoring system. We thus stratified, with high concordance, three groups of patients on a graduated scale of recurrence-related survival. Conclusion: We constructed a preoperative risk score to estimate outcomes after liver resection in NCL-HCC patients. Hence, this score makes it possible to rationally stratify patients based on recurrence risk assessment for better treatment planning.
Association between Helicobacter pylori infection, mismatch repair, HER2 and tumor-infiltrating lymphocytes in gastric cancer
(Baishideng Publishing Group Inc, 2024) Castaneda, CA; Castillo, M; Bernabe, LA; Sanchez, J; Fassan, M; Tello, K; Wistuba, II; Passiuri, IC; Ruiz, E; Sanchez, J; Barreda, F; Valdivia, D; Bazan, Y; Abad-Licham, M; Mengoa, C; Fuentes, H; Montenegro, P; Poquioma, E; Alatrista, R; Flores, CJ; Taxa, L
BACKGROUND The influence of Helicobacter-pylori (H. pylori) infection and the characteristics of gastric cancer (GC) on tumor-infiltrating lymphocyte (TIL) levels has not been extensively studied. Analysis of infiltrating-immune-cell subtypes as well as survival is necessary to obtain comprehensive information. AIM To determine the rates of deficient mismatch-repair (dMMR), HER2-status and H. pylori infection and their association with TIL levels in GC. METHODS Samples from 503 resected GC tumors were included and TIL levels were evaluated following the international-TILs-working-group recommendations with assessment of the intratumoral (IT), stromal (ST) and invasive-border (IB) compartments. The density of CD3, CD8 and CD163 immune cells, and dMMR and HER2-status were determined by immunohistochemistry (IHC). H. pylori infection was evaluated by routine histology and quantitative PCR (qPCR) in a subset of samples. RESULTS dMMR was found in 34.4%, HER2+ in 5% and H. pylori-positive in 55.7% of samples. High IT-TIL was associated with grade-3 (P = 0.038), while ST-TIL with grade-1 (P < 0.001), intestinal-histology (P < 0.001) and no-recurrence (P = 0.003). dMMR was associated with high TIL levels in the ST (P = 0.019) and IB (P = 0.01) compartments, and STCD3 (P = 0.049) and ST-CD8 (P = 0.05) densities. HER2-was associated with high IT-CD8 (P = 0.009). H. pylorinegative was associated with high IT-TIL levels (P = 0.009) when assessed by routine-histology, and with high TIL levels in the 3 compartments (P = 0.002-0.047) and CD8 density in the IT and ST compartments (P = 0.001) when assessed by qPCR. A longer overall survival was associated with low IT-CD163 (P = 0.003) and CD8/CD3 (P = 0.001 in IT and P = 0.002 in ST) and high IT-CD3 (P = 0.021), ST-CD3 (P = 0.003) and CD3/CD163 (P = 0.002). CONCLUSION TIL levels were related to dMMR and H. pylori-negativity. Low CD8/CD3 and high CD163/CD3 were associated with lower recurrence and longer survival.
Carcinoma hepatocelular en Perú: una descripción molecular de un cuadro clínico atípico
(Asociacion Mexicana de Gastroenterologia, 2024) Contreras-Mancilla, J; Cerapio, JP; Ruiz, E; Fernández, R; Casavilca-Zambrano, S; Machicado, C; Fournié, JJ; Pineau, P; Bertani, S
Introduction: Hepatocellular carcinoma (HCC) is the third most frequent cancer of digestive tract tumors in Peru, with a high mortality rate of 17.7 per 100,000 inhabitants. A significant number of HCC cases in Peru do not follow the classic clinical epidemiology of the disease described in other parts of the world. Those patients present with a distinct transcriptome profile and a singular tumor process, suggesting a particular type of hepatocarcinogenesis in a portion of the Peruvian population. Aim: Our aim was to understand the clinical and biologic involvement of the epigenetic profile (methylation) and gene expression (transcriptome) of HCC in Peruvian patients. Methods: HCC and liver transcriptome and DNA methylation profiles were evaluated in 74 Peruvian patients. Results: When grouped by age, there was greater DNA methylation in younger patients with HCC but no differences with respect to the transcriptomic profile. A high prevalence of the hepatitis B virus (HBV) (> 90%) was also observed in the younger patients with HCC. Enrichment analyses in both molecular profiles pinpointed PRC2 as an important molecular effector of that liver tumor process in Peruvian patients. Conclusion: HCC in Peruvian patients has a unique molecular profile, associated with the presence of HBV, as well as overall DNA hypermethylation related to undifferentiated liver cells or cellular reprogramming.
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.
On the risk of further excluding outcast patient populations in South America
(Elsevier Espana S.L.U, 2023) Ruiz, E; Fernández, R; Berrospi, F; Casavilca-Zambrano, S; Contreras-Mancilla, J; Cerapio, JP; Pineau, P; Bertani, S
It is with great interest that we read the article by Farah and colleagues on the epidemiological transition at work regarding risk factors for hepatocellular carcinoma (HCC) in South America [1]. In this study, the authors compiled data from 339 patients seen between 2019 and 2021 in six countries of the region, with Peruvian patients accounting for the most significant proportion, i.e., 125 HCC cases (37%) collected at one general services hospital.
Prevalence of Helicobacter pylori Infection, Its Virulent Genotypes, and Epstein-Barr Virus in Peruvian Patients With Chronic Gastritis and Gastric Cancer
(American Society of Clinical Oncology, 2019) Castaneda, Carlos; Castillo, Miluska; Chavez, I; Barreda, F; Suarez, N; Nieves, J; Bernabe, LA; Valdivia, D; Ruiz, E; Dias-Neto, E; Landa-Baella, MP; Bazan, Y; Rengifo, CA; Montenegro, P
Purpose: Helicobacter pylori (HP) and Epstein Barr virus (EBV) infections induce chronic gastritis (CG) and are accepted carcinogenics of gastric cancer (GC). Our objective for this study was to determine the prevalence of these agents and clinicopathological features of GC and CG associated with the infection. Patients and methods: A single-center cohort of 375 Peruvian patients with GC and 165 control subjects with CG were analyzed. Evaluation of HP and EBV genes was performed through quantitative polymerase chain reaction. Results: Prevalence of HP was 62.9% in the whole population and 60.8% in the GC subset. The cagA gene was detected in 79.9%; vacAs1 and vacAm1 alleles in 41.6% and 60.7%, respectively; and concurrent expression of vacAs1 and vacAm1 in 30.4% of infected patients in the whole series. The prevalence of EBV was 14.1% in the whole population and was higher in GC (P < .001). Coinfection of HP and EBV was found in 7.8% and was also higher in GC in univariate (P < .001) and multivariate (P = .011) analyses. Infection rates of HP and EBV were not associated with a geographic location in the whole series. Few clinicopathological features have been associated with infectious status. Conclusion: Prevalence of HP infection and virulent strains are high in the Peruvian population. Infection by EBV was more frequent in patients with GC.
Surgical Technique Left gastric vein to adrenal vein anastomosis: intraoperative solution for gastric venous congestion following extended distal pancreatectomy
(Oxford University Press, 2024) Fernández-Placencia, RM; Vásquez, CL-V; Belón-Supo, J; Ruiz, E; Berrospi, F; Celis-Zapata, J
Extended distal pancreatectomy often requires resection of vascular structures and adjacent organs, potentially leading to gastric venous congestion. This case report describes a 49-year-old female who underwent radical antegrade modular pancreatosplenectomy for pancreatic ductal adenocarcinoma. During the procedure, segmental gastric venous congestion was observed and resolved by anastomosing the left gastric vein to the left adrenal vein. The in-hospital postoperative recovery was initially uneventful; however, the patient was readmitted because of intra-abdominal fluid collection that was managed with antibiotics. Pathological examination confirmed moderately differentiated ductal adenocarcinoma with lymphovascular invasion. The patient received adjuvant mFOLFIRINOX therapy and remains disease-free 12 months after surgery with adequate patency of the anastomosis. This case highlights the importance of recognizing and addressing gastric venous congestion during radical antegrade modular pancreatosplenectomy to prevent complications, such as delayed gastric emptying or gastric necrosis, and proposes left gastric vein to left adrenal vein anastomosis as an effective intraoperative solution.