The role of gastrointestinal endoscopy in Kaposi sarcoma Gonzalez-Ballesteros, Patricia; de la Mora Levy, José Guillermo; Amaya-Fragoso, Edgardo ...
Revista española de enfermedades digestivas,
12/2023, Letnik:
115, Številka:
12
Journal Article
Recenzirano
Odprti dostop
We are writing to make endoscopists aware of the paramount of a prompt diagnosis of gastrointestinal Kaposi sarcoma (GI-KS). Patients with GI involvement have a two to five times higher risk of death ...and will benefit from chemotherapy to improve their survival. However, current evidence found that one out of three patients might have a false negative result even with HHV-8 since other entities such as gastrointestinal stromal tumors, angiosarcoma, and lymphoma shared macroscopic and histopathological characteristics. These cause a delay in treatment and significantly worsen the prognosis. We observed a trend for a positive diagnosis from ulcers and nodules. To our knowledge, this is the largest cohort of patients with GI-KS in the world. Our study suggests that in cases where a complete immunochemistry panel for KS is not available, HHV-8 remains as a bare minimum. However, other gastrointestinal lesions shared histopathological characteristics. Therefore, we suggest taking biopsies from nodular and ulcer-type lesions to increase the probability to establish a histopathological diagnosis.
Historic demography changes of plant species adapted to New World arid environments could be consistent with either the Glacial Refugium Hypothesis (GRH), which posits that populations contracted to ...refuges during the cold-dry glacial and expanded in warm-humid interglacial periods, or with the Interglacial Refugium Hypothesis (IRH), which suggests that populations contracted during interglacials and expanded in glacial times. These contrasting hypotheses are developed in the present study for the giant columnar cactus Cephalocereus columna-trajani in the intertropical Mexican drylands where the effects of Late Quaternary climatic changes on phylogeography of cacti remain largely unknown. In order to determine if the historic demography and phylogeographic structure of the species are consistent with either hypothesis, sequences of the chloroplast regions psbA-trnH and trnT-trnL from 110 individuals from 10 populations comprising the full distribution range of this species were analysed. Standard estimators of genetic diversity and structure were calculated. The historic demography was analysed using a Bayesian approach and the palaeodistribution was derived from ecological niche modelling to determine if, in the arid environments of south-central Mexico, glacial-interglacial cycles drove the genetic divergence and diversification of this species. Results reveal low but statistically significant population differentiation (FST = 0.124, P < 0.001), although very clear geographic clusters are not formed. Genetic diversity, haplotype network and Approximate Bayesian Computation (ABC) demographic analyses suggest a population expansion estimated to have taken place in the Last Interglacial (123.04 kya, 95% CI 115.3-130.03). The species palaeodistribution is consistent with the ABC analyses and indicates that the potential area of palaedistribution and climatic suitability were larger during the Last Interglacial and Holocene than in the Last Glacial Maximum. Overall, these results suggest that C. columna-trajani experienced an expansion following the warm conditions of interglacials, in accordance with the GRH.
Background Recurrent genetic alterations contributing to leukemogenesis have been identified in pediatric B-cell Acute Lymphoblastic Leukemia (B-ALL), and some are useful for refining classification, ...prognosis, and treatment selection. IKZF1 plus is a complex biomarker associated with a poor prognosis. It is characterized by IKZF1 deletion coexisting with PAX5 , CDKN2A/2B , or PAR1 region deletions. The mutational spectrum and clinical impact of these alterations have scarcely been explored in Mexican pediatric patients with B-ALL. Here, we report the frequency of the IKZF1 plus profile and the mutational spectrum of IKZF1, PAX5, CDKN2A/2B , and ERG genes and evaluate their impact on overall survival (OS) in a group of patients with B-ALL. Methods A total of 206 pediatric patients with de novo B-ALL were included. DNA was obtained from bone marrow samples at diagnosis before treatment initiation. A custom-designed next-generation sequencing panel was used for mutational analysis. Kaplan-Meier analysis was used for OS estimation. Results We identified the IKZF1 plus profile in 21.8% of patients, which was higher than that previously reported in other studies. A significantly older age ( p=0.04 ), a trend toward high-risk stratification ( p=0.06 ), and a decrease in 5-year Overall Survival (OS) ( p=0.009 ) were observed, although heterogeneous treatment protocols in our cohort would have impacted OS. A mutation frequency higher than that reported was found for IKZF1 (35.9%) and CDKN2A/2B (35.9%) but lower for PAX5 (26.6%). IKZF1 MUT group was older at diagnosis ( p=0.0002 ), and most of them were classified as high-risk (73.8%, p=0.02 ), while patients with CDKN2A/2B MUT had a higher leukocyte count ( p=0.01 ) and a tendency toward a higher percentage of blasts (98.6%, >50% blasts, p=0.05 ) than the non-mutated patients. A decrease in OS was found in IKZF1 MUT and CDKN2A/2B MUT patients, but the significance was lost after IKZF1 plus was removed. Discussion Our findings demonstrated that Mexican patients with B-ALL have a higher prevalence of genetic markers associated with poor outcomes. Incorporating genomic methodologies into the diagnostic process, a significant unmet need in low- and mid-income countries, will allow a comprehensive identification of relevant alterations, improving disease classification, treatment selection, and the general outcome.
B-cell acute lymphoblastic leukemia (B-ALL) is one of the most common childhood cancers worldwide. Although most cases are sporadic, some familial forms, inherited as autosomal dominant traits with ...incomplete penetrance, have been described over the last few years. Germline pathogenic variants in transcription factors such as
, and
have been identified as causal in familial forms. The proband was a 7-year-old Mexican girl diagnosed with high-risk B-ALL at five years and 11 months of age. Family history showed that the proband's mother had high-risk B-ALL at 16 months of age. She received chemotherapy and was discharged at nine years of age without any evidence of recurrence of leukemia. The proband's father was outside the family nucleus, but no history of leukemia or cancer was present up to the last contact with the mother. We performed exome sequencing on the proband and the proband's mother and identified the
variant NM_016734.3:c.963del: p.(Ala322LeufsTer11), located in the transactivation domain of the PAX5 protein. The variant was classified as probably pathogenic according to the ACMG criteria. To the best of our knowledge, this is the first Mexican family with an inherited increased risk of childhood B-ALL caused by a novel germline pathogenic variant of
. Identifying individuals with a hereditary predisposition to cancer is essential for modern oncological practice. Individuals at high risk of leukemia would benefit from hematopoietic stem cell transplantation, but family members carrying the pathogenic variant should be excluded as hematopoietic stem cell donors.
Latin American countries are heterogeneous in terms of lung cancer incidence and exposure to potential carcinogens. We evaluated the frequency and clinical characteristics of ALK rearrangements ...(ALKr) in Latin America.
A total of 5,130 lung cancer patients from 10 Latin American countries were screened for inclusion. ALKr detection was performed by fluorescence in situ hybridization (FISH), immunohistochemistry (IHC), and real-time reverse transcriptase-polymerase chain reaction (RT-PCR) to assess method variability. Demographic and clinicopathologic characteristics were analyzed.
Among the 5,130 patients screened, 8.4% (n = 433) had nonevaluable FISH tests. Evaluable FISH analyses revealed positive ALKr in 6.8% (320/4,697) of the study population, which included patients from 9 countries. ALKr distribution for each country was: Mexico 7.6% (79/1,034), Colombia 4.1% (10/242), Argentina 6.0% (153/2,534), Costa Rica 9.5% (13/137), Panama 4.4% (5/114), Uruguay 5.4% (2/37), Chile 8.6% (16/185), Venezuela 8.9% (13/146), and Peru 10.8% (29/268). RT-PCR showed high positive (83.6%) and negative (99.7%) predictive values when compared to the gold standard FISH. In contrast, IHC only showed a high negative predictive value (94.6%).
Although there is a clear country and continental variability in terms of ALKr frequency, this difference is not significant and the overall incidence of ALKr in Latin America does not differ from the rest of the world.
•Insufficient responders presented thinner prefrontal cortexes•Full responders had a thicker right dorsolateral prefrontal cortex•Subjects with mixed features had increased odds of achieving full ...response
Valproate compositions are frequently used to treat bipolar disorder (BD); however, 87% of patients do not report full response in the long-term. There is scarce information about the clinical features and brain structural characteristics of long-term treatment response (LTTR) to this medication. In this study, we aim to evaluate the clinical characteristics and prefrontal cortical thickness (CT) of LTTR to valproate in BD. We evaluated 30 BD outpatients on valproate treatment, and 20 controls with a 3T T1-weighted 3D brain scan and Alda's scale for LTTR. An analysis of covariance was used to evaluate CT measures and a logistic regression was conducted to predict the full response (FR) using clinical features and CT measures. Patients with an insufficient response (IR) reported thinner right frontal eye fields, anterior and dorsolateral prefrontal cortexes compared with controls. FR patients presented thicker right dorsolateral prefrontal cortex than IR and no differences with controls. Patients with mixed features presented increased odds of achieving FR, while CT measures reported non-significant results. This is the first study to report mixed features as a clinical predictor of valproate LTTR. Our findings also suggest better preservation of the right prefrontal cortex of subjects with FR to valproate.
Evidence regarding long-term therapeutic outcomes and disease-specific survival (DSS) in Extramammary Paget's disease (EMPD) is limited.
To assess the DSS and outcomes of surgical and nonsurgical ...therapeutic modalities in a large cohort of EMPD patients.
Retrospective chart review of EMPD patients from 20 Spanish tertiary care hospitals.
Data on 249 patients with a median follow-up of 60 months were analyzed. The estimated 5-, 10-, and 15-year DSS was 95.9%, 92.9%, and 88.5%, respectively. A significantly lower DSS was observed in patients showing deep dermal invasion (≥1 mm) or metastatic disease (P < .05). A ≥50% reduction in EMPD lesion size was achieved in 100% and 75.3% of patients treated with surgery and topical therapies, respectively. Tumor-free resection margins were obtained in 42.4% of the patients after wide local excision (WLE). The 5-year recurrence-free survival after Mohs micrographic surgery (MMS), WLE with tumor-free margins, WLE with positive margins, radiotherapy, and topical treatments was 63.0%, 51.4%, 20.4%, 30.1%, and 20.8%, respectively.
Retrospective design.
EMPD is usually a chronic condition with favorable prognosis. MMS represents the therapeutic alternative with the greatest efficacy for the disease. Recurrence rates in patients with positive margins after WLE are similar to the ones observed in patients treated with topical agents.
Background
The use of Mohs micrographic surgery (MMS) for rare cutaneous tumors is poorly defined. We aim to describe the demographics, tumor presentation and topography, surgery characteristics and ...complications of MMS for rare cutaneous tumors in a national registry.
Methods
Prospective cohort study of patients treated with MMS in Spain between July 2013 and June 2018. The inclusion criteria were patients with cutaneous tumors with final diagnosis different from basal cell carcinoma, squamous cell carcinoma, dermatofibrosarcoma protuberans, or any kind of melanoma.
Results
Five thousand and ninety patients were recorded in the registry, from which only 73 tumors (1.4%) fulfilled the inclusion criteria: atypical fibroxanthoma (18), microcystic adnexal carcinoma (10), extramammary Paget's disease (7), Merkel cell carcinoma (5), dermatofibroma (4), trichilemmal carcinoma (4), desmoplastic trichoepithelioma (4), sebaceous carcinoma (3), leiomyosarcoma (2), porocarcinoma (2), angiosarcoma (2), trichoblastoma (1), superficial acral fibromyxoma (1), and others (10). No intra‐surgery morbidity was registered. Postsurgery complications appeared in six patients (9%) and were considered mild. Median follow‐up time was 0.9 years during which three Merkel cell carcinomas, one angiosarcoma, one microcystic adnexal carcinoma, and four others recurred (12.3%).
Conclusion
This national registry shows that rare cutaneous tumors represent a negligible part of the total MMS performed in our country with a low complication rate.
Abstract
Background
Chronic kidney disease (CKD) affects 10–13% of the population worldwide. CKD classification stratifies patients in five stages of risk for progressive renal disease based on ...estimated glomerular filtration rate (eGFR) by formulas and albuminuria. However, the reliability of formulas to reflect real renal function is a matter of debate. The effect of the error of formulas in the CKD classification is unclear, particularly for cystatin C–based equations.
Methods
We evaluated the reliability of a large number of cystatin C and/or creatinine-based formulas in the definition of the stages of CKD in 882 subjects with different clinical situations over a wide range of glomerular filtration rates (GFRs) (4.2–173.7 mL/min).
Results
Misclassification was a constant for all 61 formulas evaluated and averaged 50% for creatinine-based and 35% for cystatin C–based equations. Most of the cases were misclassified as one stage higher or lower. However, in 10% of the subjects, one stage was skipped and patients were classified two stages above or below their real stage. No clinically relevant improvement was observed with cystatin C–based formulas compared with those based on creatinine.
Conclusions
The error in the classification of CKD stages by formulas was extremely common. Our study questions the reliability of both cystatin C and creatinine-based formulas to correctly classify CKD stages. Thus the correct classification of CKD stages based on estimated GFR is a matter of chance. This is a strong limitation in evaluating the severity of renal disease, the risk for progression and the evolution of renal dysfunction over time.
Aims
To study programmed death ligand 1 (PD‐L1) expression, tumour‐infiltrating T lymphocytes (TILs) and the molecular context in patients with early‐stage squamous cell lung carcinomas (SCCs).
...Methods and results
The study included samples from 40 patients (discovery cohort) and 29 patients (validation cohort) diagnosed with early‐stage SCC. PD‐L1 immunohistochemistry (IHC) was performed with three commercially available clones (E1L3N, SP263 and SP142). CD8+ TILs were scored with a digital algorithm. All tumours were analysed with targeted next‐generation sequencing (NGS). Additionally, TP53 mutations were investigated with direct sequencing. In both cohorts, we observed a significant association between CD8+ TILs density and high PD‐L1 IHC expression in tumour cells (TCs). Furthermore, high SP142 PD‐L1 expression in immune cells (ICs) was also associated significantly with CD8+ TILs density. Therefore, CD8+ TILs density discriminated between patients with high versus low PD‐L1 IHC expression with excellent sensitivity and specificity. Interestingly, the highest percentages of PD‐L1‐positive TCs with the three antibodies were found in samples with cyclin‐dependent kinase 6 (CDK6) amplification, with high amplification of proto‐oncogene C‐Myc (CMYC) or with cyclin D1–PI3 kinase subunit alpha (CCND1–PIK3CA) co‐amplification. High SP142 PD‐L1 IHC expression in ICs showed a non‐significant correlation with TP53 mutations. Conversely, most cases with fibroblast growth factor receptor 1 (FGFR1) amplification were negative for all PD‐L1 clones.
Conclusions
Our preliminary results support the use of digital CD8+ TILs scoring and targeted NGS alongside PD‐L1 expression. The approach presented herein could help define patients with SCCs candidates to immune checkpoints inhibitors.
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