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Últimos avances en el tratamiento neoadyuvante de cáncer de vejiga
No full textCisplatin-based neoadjuvant therapy has shown clear benefits in clinical stage II or IIIA muscle invasive bladder cancer (MIBC), achieving an impact in progression-free survival and overall survival. This updated review focuses on neoadjuvant therapy for MIBC, including the current recommendations from international and/or local practice guidelines, as well as studies of new therapeutic agents (immunotherapy, targeted therapy), on top of research on potential biomarkers that may predict response to immunotherapy. © 2022 Acta Medica Peruana. All rights reserved
The Senologic International Society Survey on Ductal Carcinoma In Situ: Present and Future
No full textObjective: Therapeutic management of ductal carcinoma in situ (DCIS) is heterogeneous among countries worldwide, and some treatment indications are still controversial. To investigate DCIS management in different countriesidentify both consensual practices and controversial topicsand survey opinions about the future management of DCIS. Materials and Methods: The Senologic International Society network members participated to an online survey using a questionnaire, between November 2021 and February 2022. Results: Twenty-two responses from 20 different countries showed that organized breast cancer screening programs were present for 87% participants, and DCIS cases represented 13.7% of all breast cancers. Most participants used the grade classification (100%), the morphological classification (78%) and performed immunohistochemistry assays (73%). In case of conservative treatment, the mean re-excision rate was 10.3% and clear margins of mean 2.5 mm were considered healthy. Radical mastectomy rate was 35.5% with a breast reconstruction rate of 53%. Tumor bed boost indications were heterogeneous, and 73% of participants indicated hormone therapy for hormone-positive DCIS. Surgery and radiotherapy omission for some low-risk DCIS were considered by 73% of participants. Multigene assays were used by 43% of participants. Concerning future changes in DCIS management, participants mostly answered surgical de-escalation (48%), radiotherapy de-escalation (35) and/or active surveillance for some cases (22%). Conclusion: This survey provided an overview of the current practices of DCIS management worldwide. It showed that some areas are rather consensual: incidence increases over time, treatment in young women, pathological classifications, definition of healthy margins, the skin-sparing mastectomy and immediate breast reconstruction. However, some topics are still debated and result in heterogeneous practices, such as evolution in the age of diagnosis, the benefit of de-escalation in low-risk DCIS among elderly women, indications for hormone therapy, radiotherapy omission, or multigene assays. Further evidence is needed to reach consensus on these points, and innovative approaches are still under evaluation in clinical trials. The International Senologic Society, by its members, encourages precision medicine and personalized treatments for DCIS, to avoid overtreatment and overdiagnosis, and provide better healthcare to women with DCIS
First Isolates of OXA-48-Like Carbapenemase-Producing Enterobacteriaceae in A Specialized Cancer Center
No full textBackground: OXA-48-like carbapenemases have been found in a growing and varied number of carbapenemase-producing Enterobacteriaceae (CPE) isolates, and they are spreading to several countries. Although this oxacillinase leads to weak resistance to carbapenems without affecting broad-spectrum cephalosporin activity, when they are associated with other resistance mechanisms, the level of resistance to these antibiotics may be significantly higher. This weak resistance against carbapenems and cephalosporins, along with the absence of other resistance mechanisms, could render OXA-48-like harboring isolates undetected in the laboratory routine. In addition, the lack of a specific screening test for this enzyme complicates the detection of these isolates. This report characterizes the first isolates of OXA-48-like CPE detected in our laboratory. Materials and Methods: The study was carried out at the Instituto Nacional de Enfermedades Neoplasicas, Lima - Peru, between March and December 2021. OXA-48-like CPE isolates were detected as part of the routine microbiological study, and clinical data were obtained by reviewing medical records. The automated microbiological system provides the bacterial identification and antimicrobial susceptibility profile by the dilution method. Additionally, the column chromatography test is used to detect carbapenemase enzymes, including OXA-48-like. Finally, the molecular identification of the OXA-48-like enzyme was carried out by Polymerase Chain Reaction PCR amplification for the blaOXA-48-like. Results: Seven OXA-48-like CPE strains were isolated. Notably, in all cases, the automated system issued a minimum inhibitory concentration (MIC) of ≥1 ug/mL for ertapenem and a MIC of >64/4 ug/mL for piperacillin/tazobactam. In addition, resistance category to imipenem and meropenem was found (2/7), at least one indeterminate category for any of these carbapenems (5/7), and other serine β-lactamases such as Extended-spectrum beta-lactamases (3/7) and AmpC (3/7). The immunochromatographic study confirmed the presence of the OXA-48-like enzyme in all isolates, while class A and class B were ruled out for them. Finally, the multiplex PCR, for the five isolates that could be recovered, showed amplification for carbapenemase OXA-48-like, while none of the other carpabemases was amplified for class A or class B carbapenemase genes. Conclusion: We confirm the emergence of OXA-48-like CPE isolates in our cancer center and highlight the need to implement surveillance and detection measures of these strains, for controlling their dissemination. We found practical and inexpensive methodologies for the detection of OXA-48-like CPE: (1) the finding of resistance to ertapenem and piperacillin/ tazobactam in the antibiogram in the absence of class A and B carbapenemases, for screening and (2) immunochromatographic study, for confirmation
Gene Expression Signatures for the Accurate Diagnosis of Peripheral T-Cell Lymphoma Entities in the Routine Clinical Practice
No full textPURPOSE Peripheral T-cell lymphoma (PTCL) includes heterogeneous clinicopathologic entities with numerous diagnostic and treatment challenges. We previously defined robust transcriptomic signatures that distinguish common PTCL entities and identified two novel biologic and prognostic PTCL-not otherwise specified subtypes (PTCL-TBX21 and PTCL-GATA3). We aimed to consolidate a gene expression-based subclassification using formalin-fixed, paraffin-embedded (FFPE) tissues to improve the accuracy and precision in PTCL diagnosis. MATERIALS AND METHODS We assembled a well-characterized PTCL training cohort (n = 105) with gene expression profiling data to derive a diagnostic signature using fresh-frozen tissue on the HG-U133plus2.0 platform (Affymetrix, Inc, Santa Clara, CA) subsequently validated using matched FFPE tissues in a digital gene expression profiling platform (nCounter, NanoString Technologies, Inc, Seattle, WA). Statistical filtering approaches were applied to refine the transcriptomic signatures and then validated in another PTCL cohort (n = 140) with rigorous pathology review and ancillary assays. RESULTS In the training cohort, the refined transcriptomic classifier in FFPE tissues showed high sensitivity (> 80%), specificity (> 95%), and accuracy (> 94%) for PTCL subclassification compared with the fresh-frozen-derived diagnostic model and showed high reproducibility between three independent laboratories. In the validation cohort, the transcriptional classifier matched the pathology diagnosis rendered by three expert hematopathologists in 85% (n = 119) of the cases, showed borderline association with the molecular signatures in 6% (n = 8), and disagreed in 8% (n = 11). The classifier improved the pathology diagnosis in two cases, validated by clinical findings. Of the 11 cases with disagreements, four had a molecular classification that may provide an improvement over pathology diagnosis on the basis of overall transcriptomic and morphological features. The molecular subclassification provided a comprehensive molecular characterization of PTCL subtypes, including viral etiologic factors and translocation partners. CONCLUSION We developed a novel transcriptomic approach for PTCL subclassification that facilitates translation into clinical practice with higher precision and uniformity than conventional pathology diagnosis
Tumor miofibroblástico primario gástrico en un adulto en el Perú: reporte de caso y revisión de la literatura
No full textPrimary gastric inflammatory myofibroblastic tumor is a rare neoplasm developed from mesen-chymal stem cells, infrequently discussed in the scientific literature. Clinical diagnosis through endoscopy and pathology is challenging for the medical team. We report the case of a female patient with gastric obstruction syndrome due to a 10 cm tumor diagnosed with this disease by histology and immunohistochemistry
Twelve-month observational study of children with cancer in 41 countries during the COVID-19 pandemic
No full textIntroduction Childhood cancer is a leading cause of death. It is unclear whether the COVID-19 pandemic has impacted childhood cancer mortality. In this study, we aimed to establish all-cause mortality rates for childhood cancers during the COVID-19 pandemic and determine the factors associated with mortality. Methods Prospective cohort study in 109 institutions in 41 countries. Inclusion criteria: children <18 years who were newly diagnosed with or undergoing active treatment for acute lymphoblastic leukaemia, non-Hodgkin's lymphoma, Hodgkin lymphoma, retinoblastoma, Wilms tumour, glioma, osteosarcoma, Ewing sarcoma, rhabdomyosarcoma, medulloblastoma and neuroblastoma. Of 2327 cases, 2118 patients were included in the study. The primary outcome measure was all-cause mortality at 30 days, 90 days and 12 months. Results All-cause mortality was 3.4% (n=71/2084) at 30-day follow-up, 5.7% (n=113/1969) at 90-day follow-up and 13.0% (n=206/1581) at 12-month follow-up. The median time from diagnosis to multidisciplinary team (MDT) plan was longest in low-income countries (7 days, IQR 3-11). Multivariable analysis revealed several factors associated with 12-month mortality, including low-income (OR 6.99 (95% CI 2.49 to 19.68)p<0.001), lower middle income (OR 3.32 (95% CI 1.96 to 5.61)p<0.001) and upper middle income (OR 3.49 (95% CI 2.02 to 6.03)p<0.001) country status and chemotherapy (OR 0.55 (95% CI 0.36 to 0.86)p=0.008) and immunotherapy (OR 0.27 (95% CI 0.08 to 0.91)p=0.035) within 30 days from MDT plan. Multivariable analysis revealed laboratory-confirmed SARS-CoV-2 infection (OR 5.33 (95% CI 1.19 to 23.84)p=0.029) was associated with 30-day mortality. Conclusions Children with cancer are more likely to die within 30 days if infected with SARS-CoV-2. However, timely treatment reduced odds of death. This report provides crucial information to balance the benefits of providing anticancer therapy against the risks of SARS-CoV-2 infection in children with cancer. © 2022 BMJ Publishing Group. All rights reserved
Comparative Profiling of Circulating Exosomal Small RNAs Derived From Peruvian Patients With Tuberculosis and Pulmonary Adenocarcinoma
No full textTuberculosis (TB) is one of the most fatal infectious diseases, caused by the aerobic bacteria Mycobacterium tuberculosis. It is estimated that one-third of the world’s population is infected with the latent (LTB) version of this disease, with only 5-10% of infected individuals developing its active (ATB) form. Pulmonary adenocarcinoma (PA) is the most common and diverse form of primary lung carcinoma. The simultaneous or sequential occurrence of TB and lung cancer in patients has been widely reported and is known to be an issue for diagnosis and surgical treatment. Raising evidence shows that patients cured of TB represent a group at risk for developing PA. In this work, using sRNA-sequencing, we evaluated the expression patterns of circulating small RNAs available in exosomes extracted from blood samples of Peruvian patients affected by latent tuberculosis, active tuberculosis, or pulmonary adenocarcinoma. Differential expression analysis revealed a set of 24 microRNAs perturbed in these diseases, revealing potential biomarker candidates for the Peruvian population. Most of these miRNAs are normally expressed in healthy lung tissue and are potential regulators of different shared and unique KEGG pathways related to cancers, infectious diseases, and immunology
GATA-3 is a proto-oncogene in T-cell lymphoproliferative neoplasms
No full textNeoplasms originating from thymic T-cell progenitors and post-thymic mature T-cell subsets account for a minority of lymphoproliferative neoplasms. These T-cell derived neoplasms, while molecularly and genetically heterogeneous, exploit transcription factors and signaling pathways that are critically important in normal T-cell biology, including those implicated in antigen-, costimulatory-, and cytokine-receptor signaling. The transcription factor GATA-3 regulates the growth and proliferation of both immature and mature T cells and has recently been implicated in T-cell neoplasms, including the most common mature T-cell lymphoma observed in much of the Western world. Here we show that GATA-3 is a proto-oncogene across the spectrum of T-cell neoplasms, including those derived from T-cell progenitors and their mature progeny, and further define the transcriptional programs that are GATA-3 dependent, which include therapeutically targetable gene products. The discovery that p300-dependent acetylation regulates GATA-3 mediated transcription by attenuating DNA binding has novel therapeutic implications. As most patients afflicted with GATA-3 driven T-cell neoplasms will succumb to their disease within a few years of diagnosis, these findings suggest opportunities to improve outcomes for these patients
Gastric collision tumour with probable ectopic pancreatic origin
No full textIntroduction: Mixed histology tumours are rarely found in the stomach. Of these, collision tumours are mainly composed of adenocarcinomas and sarcomas or lymphomas. This is the seventh case reported in the literature of an acinar cell carcinoma arising from an ectopic pancreas located in the stomach and the first described within a collision tumour. Clinical case: We present the case of a 58-year-old female patient diagnosed with gastric cancer who, after undergoing a total gastrectomy, presented with a pathology report describing findings compatible with gastric collision tumour with components of tubular adenocarcinoma and acinar cell carcinoma of probable pancreatic ectopic aetiology. Discussion: At the beginning of the 20th century, collision tumours were rarely described. Those located in the stomach are an infrequent pathology and are rarely diagnosed preoperatively. A collision tumour is composed of two independent neoplastic tissue with tumour areas separated in two different histological patterns and, in case of metastasis, this separation must also be clearly identified. There are different theories about its carcinogenesis and the debate regarding the ideal treatment is still ongoing. Conclusion: This is the first report of a malignant gastric tumour with probable heterotopic pancreatic origin that collides with gastric adenocarcinoma. Copyright: © 2022 the authorslicensee ecancermedicalscience
Factors influencing outcomes of older children with medulloblastoma over 15 years in Peru, a resource-limited setting
No full textBackground: Medulloblastoma is the most common malignant brain tumor in children. While survival has improved in high-income countries (HIC), the outcomes for patients in low-to-middle-income countries (LMIC) are unclear. Therefore, we sought to determine the survival of children with medulloblastoma at the Instituto Nacional de Enfermedades Neoplasicas (INEN) between 1997 and 2013 in Peru. Methods: Between 1997 and 2013, data from 103 children older than 3 years with medulloblastoma were analyzed. Fourteen patients were excluded. The patients were split into two distinct cohorts, 1997–2008 and 2009–2013, corresponding with chemotherapy regimen changes. Event-free (EFS) and overall survival (OS) were calculated using the Kaplan–Meier method, whereas prognostic factors were determined by univariate analysis (log-rank test). Results: Eighty-nine patients were includedmedian age was 8.1 years (range: 3–13.9 years). The 5-year OS was 62% (95% CI: 53%–74%), while EFS was 57% (95% CI: 48%–69%). The variables adversely affecting survival were anaplastic histology (compared to desmoplasticOS: HR = 3.4, p =.03), metastasis (OS: HR = 3.5, p =.01EFS: HR = 4.3, p =.004), delay in radiation therapy of 31–60 days (compared to ≤30 daysEFS: HR = 2.1, p =.04), and treatment 2009–2013 cohort (OS: HR = 2.2, p =.02EFS: HR = 2.0, p =.03). Conclusions: Outcomes for medulloblastoma at INEN were low compared with HIC. Anaplastic subtype, metastasis at diagnosis, delay in radiation therapy, and treatment in the period 2009–2013 negatively affected the outcomes in our study. Multidisciplinary teamwork, timely delivery of treatment, and partnerships with loco-regional groups and colleagues in HIC is likely beneficial