Eloy Ruiz

A peculiar mutation spectrum emerging from young peruvian patients with hepatocellular carcinoma

Hepatocellular carcinoma usually afflicts individuals in their later years following longstanding liver disease. In Peru, hepatocellular carcinoma exists in a unique clinical presentation, which affects patients around age 25 with a normal, healthy liver. In order to deepen our understanding of the molecular processes ongoing in Peruvian liver tumors, mutation spectrum analysis was carried out on hepatocellular carcinomas from 80 Peruvian patients. Sequencing analysis focused on nine genes typically altered during liver carcinogenesis, i.e. ARID2, AXIN1, BRAF, CTNNB1, NFE2L2, H/K/N-RAS, and TP53. We also assessed the transcription level of factors involved in the control of the alpha-fetoprotein expression and the Hippo signaling pathway that controls contact inhibition in metazoans. The mutation spectrum of Peruvian patients was unique with a major class of alterations represented by Insertions/Deletions. There were no changes at hepatocellular carcinoma-associated mutation hotspots in more than half of the specimens analyzed. Furthermore, our findings support the theory of a consistent collapse in the Hippo axis, as well as an expression of the stemness factor NANOG in high alpha-fetoprotein-expressing hepatocellular carcinomas. These results confirm the specificity of Peruvian hepatocellular carcinoma at the molecular genetic level. The present study emphasizes the necessity to widen cancer research to include historically neglected patients from South America, and more broadly the Global South, where cancer genetics and tumor presentation are divergent from canonical neoplasms.

An Atypical Age-Specific Pattern of Hepatocellular Carcinoma in Peru: A Threat for Andean Populations

Background In South America, the highest incidence of primary liver cancer is observed in Peru. However, national estimations on hepatocellular carcinoma incidence and mortality are approximated using aggregated data from surrounding countries. Thus, there is a lack of tangible information from Peru that impairs an accurate description of the local incidence, presentation, and outcomes of hepatocellular carcinoma. The present study attempts to fill this gap and assesses the clinical epidemiology of hepatocellular carcinoma in this country. Methods A retrospective cohort study was conducted by analysing the medical charts of 1,541 patients with hepatocellular carcinoma admitted between 1997 and 2010 at the Peruvian national institute for cancer. The medical records including liver function, serologic status, and tumor pathology and stage were monitored. Statistical analyses were performed in order to characterize tumor presentation according to demographic features, risk factors, and regional origin. Results Surprisingly, the age distribution of the patient population displayed bimodality corresponding to two distinct age-based subpopulations. While an older group was in keeping with the age range observed for hepatocellular carcinoma around the world, a younger population displayed an abnormally juvenile mean age of 25.5 years old. In addition, each subpopulation displayed age-specific pathophysiological and clinical characteristics. Conclusions The analysis suggests two different age-specific natural histories of hepatocellular carcinoma in the Peruvian patient population. This otherwise unusual tumor process that is ongoing in younger patients leads to the hypothesis that there may be a Peru-endemic risk factor driving hepatocarcinogenesis in the local population.

Hepatocellular carcinoma surgery outcomes in the developing world: A 20-year retrospective cohort study at the National Cancer Institute of Peru.

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.

A 13-Year Retrospective Study on Primary Liver Cancer in Cambodia: A Strikingly High Hepatitis C Occurrence among Hepatocellular Carcinoma Cases

Objectives: Hepatocellular carcinoma (HCC) is the main type of primary liver cancer (PLC) worldwide, but cholangiocarcinoma (CCA) may be predominant in some specific regions of Southeast Asia. The aim of the present study was to delineate a pattern of Cambodian PLC patients attending the Calmette Hospital in the Cambodian capital Phnom Penh. Materials and Methods: A total of 553 medical charts diagnosing PLCs from January 2003 to May 2015 were obtained from both the Oncology and Hepato-Gastroenterology Departments of the Calmette Hospital. Results: HCC was the predominant type of PLC recorded, with 511 cases (92.4%), whereas CCA represented merely 7.6% (42 cases) of the overall series. Hepatitis B virus (HBV; 44.3%) and hepatitis C virus (HCV; 43%) infection rates were similar among the HCC patients, while small subsets of CCA patients were infected with HBV (15.4%) or HCV (11.5%). Most HCC (84%) and CCA (73.8%) patients received palliative treatment only. Conclusion: The present study indicates that HCC is the main form of primary hepatic neoplasm among PLC patients attending a hospital in Cambodia. HBV and HCV infections represented equivalent burdens and major contributing factors to HCC. Therefore, the implementation of prevention programs for these infectious agents should become a priority for health policy makers in the country.

Herbal Medicine Practices of Patients With Liver Cancer in Peru: A Comprehensive Study Toward Integrative Cancer Management:

Rationale: The highest burden of liver cancer occurs in developing countries, where the use of herbal medicine (HM) is still widespread. Despite this trend, few studies have been conducted to report HM practices of patients with a hepatic tumor in the developing world. Hence, this study aimed to document the use of HM among patients with liver cancer in Peru. Study Design and Methods: A comparative behavioral epidemiological survey was conducted among liver cancer patients attending the National Cancer Institute of Peru. Information was obtained by direct interviews based on a semistructured questionnaire. The use of HM in Peruvian liver cancer patients was reported, first, regarding general consumption prior to the onset of disease, and second, after the appearance of symptoms that patients would relate to their tumor. In parallel, general consumption of HM in noncancerous people was assessed as a comparative figure. A correspondence analysis was performed to reveal potential associations between the symptoms of cancer and the specific use of HM. Results: Eighty-eight patients and 117 noncancerous individuals participated in the survey. Overall, 68.3% of the people interviewed claimed to use HM on a regular basis for general health preservation. Furthermore, 56.8% of the patients turned to plants first to treat the disorders for which they later came to the cancer care center. When compared with the number of plant species used routinely (n = 78), a selection of plants was made by patients in response to the symptoms of cancer (n = 46). At least 2 plant species, Aloe vera and Morinda citrifolia, were significantly associated with the treatment of liver cancer–related symptoms in the patient group. Conclusions: The present study is the first survey on the HM practices of patients with liver cancer in Latin America and, more broadly, in the developing world. Our findings confirm that HM remains one of the principal primary health care resources in Peru, even for a severe disease like liver cancer. These traditional, complementary and alternative medicine practices should be taken into consideration in Peruvian health programs aiming to educate the population in cancer prevention and treatment, as well as integrative cancer management.

The Latin America and the Caribbean search strategy proposal

Latin America and the Caribbean’s public health literature is not widely recognized. Science in this region has even been compared to a night sky with just a few specks of light. To make those lights as reachable as possible, we developed the Latin America and the Caribbean Search Strategy (LACSS). This is a new method to utilize our region’s health promotion results within MEDLINE/PubMed. In contrast to a typical MeSH query, LACSS retrieves up to six times more publication results regarding non-communicable diseases, neglected tropical diseases, injuries and other important public health relevant topics in the region. We believe that global health promotion will be improved in this region by improving its visibility, and this search strategy will contribute to this.

Negative serology of Fasciola hepatica infection in patients with liver cancer in Peru: a preliminary report

INTRODUCTION The etiology of several hepatocellular carcinoma (HCC) cases remains largely unknown. Although Fasciola hepatica has been associated with liver fibrosis in Latin America, it has not yet been associated with HCC. This study aimed to determine the existence of specific IgG antibodies against F. hepatica in the serum samples of HCC patients. METHODS In total, 13 serum samples from 13 HCC patients were screened using Fas2-ELISA. RESULTS Fas2-ELISA demonstrated negative results in all HCC patients included in this study. CONCLUSIONS The pre-existence of F. hepatica infection in HCC patients needs to be further investigated in epidemiological and experimental studies.

Diagnostic approach to hemolytic anemias in the adult

Even though hemolytic anemias (HAs) are not very common, their diagnosis remains a big challenge for hematologists and clinicians. We hope that this summary will contribute with valuable information about a subject that has been little described in the medical literature, and will help to clarify the diagnostic approach to guide specific treatment depending on the causative condition. It is known that HAs are a group of disorders characterized by a premature red blood cell (RBC) destruction (less than 120 days), 1,2 that exceeds the compensatory capacity of the bone marrow to increase RBC production and keep up with the loss. 1–3 Usually HAs are diagnosed through laboratory tests, however, the patients history and physical examination are crucial as they provide important information about the presence of hemolysis and its probable etiology. 3,4 For example, if in addition to the classic symptoms of anemia (paleness, fatigue, dyspnea, palpitations), findings such as familial or personal history of jaundice, exposure to toxics, leg ulcers, lymphadenopathies, hepatomegaly or splenomegaly may help to elucidate the cause of the anemia. 1,3,4 Regarding the etiology, HAs can be classified as inherited or acquired and when considering the site of hemolysis, RBCs can be destroyed in the circulation (intravascular) or within macrophages in the spleen or liver (extravascular). From the clinical perspective, HAs can be acute or chronic and according to the location of the abnormality responsible for the hemoly-sis, they may be due to intrinsic (intracorpuscular) or extrinsic (extracorpuscular) defects. 2–4 It is important to mention that most intrinsic defects are inherited, and most extrinsic ones are acquired, 2 however, there are some exceptions to this rule. For example, paroxysmal nocturnal hemoglobinuria (PNH) is an acquired HA produced by an intrinsic defect 4 and glucose-6-phosphate dehydrogenase (G6PD) deficiency is an inherited intrinsic defect that is triggered by an external factor. 2 Although there are different ways of approaching the diagnosis of HAs, it is first necessary to identify the patient with HA and collect data on hemolysis. The destruction of RBCs in HAs is characterized by an increased breakdown of hemoglobin which results in unconjugated hyperbilirubinemia clinically evidenced by jaundice, increased lactate dehydrogenase (cellular destruction), and reticulocytosis, which is a normal compensatory response of the bone marrow to the RBC loss. Additionally, decreased levels of plasma haptoglobin, a marker of RBC destruction, are evidenced 1–3 regardless the site of hemolysis (intravascular or extravascular). 5 In cases …

Liver clear cell foci and viral infection are associated with non-cirrhotic, non-fibrolamellar hepatocellular carcinoma in young patients from South America

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.

Early-onset liver cancer in South America associates with low hepatitis B virus DNA burden

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.