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First workshop on cervix cancer surgery in Latin America: A hands-on experience from Lima, Perú
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A Novel Variant in SQSTM1 Gene Causing Neurodegeneration with Ataxia, Dystonia, and Gaze Palsy in a Peruvian Family
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Biofilm formation and increased mortality among cancer patients with candidemia in a Peruvian reference center
No full textBackground: Candidemia is an invasive mycosis with an increasing global incidence and high mortality rates in cancer patients. The production of biofilms by some strains of Candida constitutes a mechanism that limits the action of antifungal agents; however, there is limited and conflicting evidence about its role in the risk of death. This study aimed to determine whether biofilm formation is associated with mortality in cancer patients with candidemia. Methods: This retrospective cohort study included patients treated at Peru’s oncologic reference center between June 2015 and October 2017. Data were collected by monitoring patients for 30 days from the diagnosis of candidemia until the date of death or hospital discharge. Statistical analyses evaluated the association between biofilm production determined by XTT reduction and mortality, adjusting for demographic, clinical, and microbiological factors assessed by the hospital routinary activities. Survival analysis and bivariate and multivariate Cox regression were used, estimating the hazard ratio (HR) as a measure of association with a significance level of p < 0.05. Results: A total of 140 patients with candidemia were included in the study. The high mortality observed on the first day of post-diagnosis follow-up (81.0%) among 21 patients who were not treated with either antifungal or antimicrobial drugs led to stratification of the analyses according to whether they received treatment. In untreated patients, there was a mortality gradient in patients infected with non-biofilm-forming strains vs. low/medium and high-level biofilm-forming strains (25.0%, 66.7% and 82.3%, respectively, p = 0.049). In treated patients, a high level of biofilm formation was associated with increased mortality (HR, 3.92; 95% p = 0.022), and this association persisted after adjusting for age, comorbidities, and hospital emergency admission (HR, 6.59; CI: 1.87–23.24, p = 0.003). Conclusions: The association between candidemia with in vitro biofilm formation and an increased risk of death consistently observed both in patients with and without treatment, provides another level of evidence for a possible causal association. The presence of comorbidities and the origin of the hospital emergency, which reflect the fragile clinical condition of the patients, and increasing age above 15 years were associated with a higher risk of death
Somatic Mutations in Latin American Breast Cancer Patients: A Systematic Review and Meta-Analysis
No full text(1) Background: Somatic mutations may be connected to the exposome, potentially playing a role in breast cancer’s development and clinical outcomes. There needs to be information regarding Latin American women specifically, as they are underrepresented in clinical trials and have limited access to somatic analysis in their countries. This study aims to systematically investigate somatic mutations in breast cancer patients from Latin America to gain a better understanding of tumor biology in the region. (2) Methods: We realize a systematic review of studies on breast cancer in 21 Latin American countries using various databases such as PubMed, Google Scholar, Web of Science, RedAlyc, Dianlet, and Biblioteca Virtual en Salud. Of 392 articles that fit the criteria, 10 studies have clinical data which can be used to create a database containing clinical and genetic information. We compared mutation frequencies across different breast cancer subtypes using statistical analyses and meta-analyses of proportions. Furthermore, we identified overexpressed biological processes and canonical pathways through functional enrichment analysis. (3) Results: 342 mutations were found in six Latin American countries, with the TP53 and PIK3CA genes being the most studied mutations. The most common PIK3CA mutation was H1047R. Functional analysis provided insights into tumor biology and potential therapies. (4) Conclusion: evaluating specific somatic mutations in the Latin American population is crucial for understanding tumor biology and determining appropriate treatment options. Combining targeted therapies may improve clinical outcomes in breast cancer. Moreover, implementing healthy lifestyle strategies in Latin America could enhance therapy effectiveness and clinical outcomes
Epithelial Expressed B7-H4 Drives Differential Immunotherapy Response in Murine and Human Breast Cancer
No full textCombinations of immune checkpoint inhibitors (ICI, including anti-PD-1/PD-L1) and chemotherapy have been FDA approved for metastatic and early-stage triple-negative breast cancer (TNBC), but most patients do not benefit. B7-H4 is a B7 family ligand with proposed immunosuppressive functions being explored as a cancer immunotherapy target and may be associated with anti-PD-L1 resistance. However, little is known about its regulation and effect on immune cell function in breast cancers. We assessed murine and human breast cancer cells to identify regulation mechanisms of B7-H4 in vitro. We used an immunocompetent anti-PD-L1–sensitive orthotopic mammary cancer model and induced ectopic expression of B7-H4. We assessed therapy response and transcriptional changes at baseline and under treatment with anti-PD-L1. We observed B7-H4 was highly associated with epithelial cell status and transcription factors and found to be regulated by PI3K activity. EMT6 tumors with cell-surface B7-H4 expression were more resistant to immunotherapy. In addition, tumor-infiltrating immune cells had reduced immune activation signaling based on transcriptomic analysis. Paradoxically, in human breast cancer, B7-H4 expression was associated with survival benefit for patients with metastatic TNBC treated with carboplatin plus anti-PD-L1 and was associated with no change in response or survival for patients with early breast cancer receiving chemotherapy plus anti-PD-1. While B7-H4 induces tumor resistance to anti-PD-L1 in murine models, there are alternative mechanisms of signaling and function in human cancers. In addition, the strong correlation of B7-H4 to epithelial cell markers suggests a potential regulatory mechanism of B7-H4 independent of PD-L1. Significance: This translational study confirms the association of B7-H4 expression with a cold immune microenvironment in breast cancer and offers preclinical studies demonstrating a potential role for B7-H4 in suppressing response to checkpoint therapy. However, analysis of two clinical trials with checkpoint inhibitors in the early and metastatic settings argue against B7-H4 as being a mechanism of clinical resistance to checkpoints, with clear implications for its candidacy as a therapeutic target. © 2024 The Authors; Published by the American Association for Cancer Research
Lesiones premalignas y cáncer de cuello uterino no relacionados al virus del papiloma humano
No full textCervical cancer is the second most common malignancy in Peruvian women. The new WHO classification divides cervical epithelial neoplasms according to the presence or absence of human papillomavirus (HPV) for both squamous and glandular types. Much has been studied on HPV-related cervical cancer and little in HPV-negative cervical cancer, which, although representing a minority group, is of different behavior and worse prognosis. This review represents an overview of this pathological with emphasis on molecular aspects. Undoubtedly, with the research of this pathology group and mainly molecular development, more specific treatments are expected. © 2024 Peruvian Society of Obstetrics and Gynecology. All rights reserved
Improved Risk Prediction in Human Papillomavirus-Associated Endocervical Adenocarcinoma Through Assessment of Binary Silva Pattern-based Classification: An International Multicenter Retrospective Observational Study Led by the International Society of Gynecological Pathologists (ISGyP)
No full textEndocervical adenocarcinomas (EACs) are a group of malignant neoplasms associated with diverse pathogenesis, morphology, and clinical behavior. As a component of the International Society of Gynecological Pathologists International Endocervical Adenocarcinoma Project, a large international retrospective cohort of EACs was generated in an effort to study potential clinicopathological features with prognostic significance that may guide treatment in these patients. In this study, we endeavored to develop a robust human papillomavirus (HPV)-associated EAC prognostic model for surgically treated International Federation of Gynecology and Obstetrics (FIGO) stage IA2 to IB3 adenocarcinomas incorporating patient age, lymphovascular space invasion (LVSI) status, FIGO stage, and pattern of invasion according to the Silva system (traditionally a 3-tier system). Recently, a 2-tier/binary Silva pattern of invasion system has been proposed whereby adenocarcinomas are classified into low-risk (pattern A/pattern B without LVSI) and high-risk (pattern B with LVSI/pattern C) categories. Our cohort comprised 792 patients with HPV-associated EAC. Multivariate analysis showed that a binary Silva pattern of invasion classification was associated with recurrence-free and disease-specific survival (P < 0.05) whereas FIGO 2018 stage I substages were not. Evaluation of the current 3-tiered system showed that disease-specific survival for those patients with pattern B tumors did not significantly differ from that for those patients with pattern C tumors, in contrast to that for those patients with pattern A tumors. These findings underscore the need for prospective studies to further investigate the prognostic significance of stage I HPV-associated EAC substaging and the inclusion of the binary Silva pattern of invasion classification (which includes LVSI status) as a component of treatment recommendations. Copyright © 2024 by the International Society of Gynecological Pathologists
Prepectoral and Retropectoral Breast-implant-Associated Anaplastic Large-cell Lymphoma
No full textSummary: Breast-implant-associated anaplastic large cell lymphoma (BIA-ALCL) is a non-Hodgkin lymphoma that arises in the space between the surface of a breast implant and the fibrous capsule that grows around the implant. Since its first description 20 years ago, almost 1000 cases of BIA-ALCL have been diagnosed worldwide. Nowadays, guidelines describe the diagnosis, staging, and treatment of this disease. We present the first two cases diagnosed and treated in Peru, demonstrating a wide range of aggressiveness of BIA-ALCL. © Plastic and Reconstructive Surgery - Global Open.All rights reserved
Feasibility of an environmental scan–based approach to collecting information about factors impacting cancer genetics services in Latin American countries
No full textObjective: Clinical cancer genetics services are expanding globally, but national policy and health care systems influence availability and implementation. Understanding the environmental factors within a country is required to appropriately implement, adapt, and evaluate cancer genetics service delivery models. An environmental scan (ES) is an approach used in business, public health, health care and other sectors to collect information about an environment or system for strategic decision making and program planning. An ES has been previously used to assess cancer genetics clinic-level factors to inform quality improvement efforts in the United States. We assessed the feasibility of using an ES to collect information about factors that may influence cancer genetics service delivery in the outer-most socio-ecological model environmental levels (policy, national agencies, healthcare systems, cultural considerations) in three Latin American countries. Methods: Oncology and Genetics care team members at three participating sites used publicly available sources and personal experiences to complete a data collection form (DCF) that included questions about subtopics: laws and policies, relevant agencies and regulations, health care systems and insurance, and cultural considerations. Time to complete the DCF and DCF completeness were used to measure ES feasibility. Results: Participating sites completed the DCF in 3 months, and most questions (average, 87.0%) were answered. Questions in the cultural considerations subtopic had the fewest answers (average, 77.8%). Conclusions: Overall, the ES was feasible and identified a lack of published literature related to cultural considerations impacting health care and genetics services uptake in Latin America. Environmental factors impact cancer genetics services, and identification of these factors will facilitate future collaborative research and genetics service delivery dissemination efforts
CNS Efficacy of Osimertinib With or Without Chemotherapy in Epidermal Growth Factor Receptor-Mutated Advanced Non-Small-Cell Lung Cancer
No full textPURPOSE We report CNS efficacy of first-line osimertinib plus chemotherapy versus osimertinib monotherapy in patients with epidermal growth factor receptor (EGFR)-mutated advanced non-small-cell lung cancer (NSCLC) from the phase III FLAURA2 study according to baseline CNS metastasis status. Methods Patients were randomly assigned to osimertinib plus platinum-pemetrexed (combination) or osimertinib monotherapy until disease progression or discontinuation. Brain scans were performed in all patients at baseline and progression and at scheduled assessments until progression for patients with baseline CNS metastases; scans were assessed by neuroradiologist CNS blinded independent central review (BICR). Results On the basis of baseline CNS BICR, 118 of 279 (combination) and 104 of 278 (monotherapy) randomly assigned patients had ≥one measurable and/or nonmeasurable CNS lesion and were included in the CNS full analysis set (cFAS); 40 of 118 and 38 of 104 had ≥one measurable target CNS lesion and were included in the post hoc CNS evaluable-for-response set (cEFR). In the cFAS, the hazard ratio (HR) for CNS progression or death was 0.58 (95% CI, 0.33 to 1.01). In patients without baseline CNS metastases, the HR for CNS progression or death was 0.67 (95% CI, 0.43 to 1.04). In the cFAS, CNS objective response rates (ORRs; 95% CI) were 73% (combination; 64 to 81) versus 69% (monotherapy; 59 to 78); 59% versus 43% had CNS complete response (CR). In the cEFR, CNS ORRs (95% CI) were 88% (73 to 96) versus 87% (72 to 96); 48% versus 16% had CNS CR. CONCLUSION Osimertinib plus platinum-pemetrexed demonstrated improved CNS efficacy compared with osimertinib monotherapy, including delaying CNS progression, irrespective of baseline CNS metastasis status. These data support this combination as a new first-line treatment for patients with EGFR-mutated advanced NSCLC, including those with CNS metastases