hTERT gene methylation in circulating DNA, tumor, and surrounding tissue in breast cancer: a prospective study

ABSTRACT BACKGROUND: The human telomerase reverse transcriptase (hTERT) enzyme, encoded by the hTERT gene, synthesizes protective telomeric sequences on chromosomes and plays a fundamental role in cancer formation. Methylation of the hTERT gene has an upregulatory effect, increasing hTERT enzyme synthesis and allowing continuous tumor cell division. OBJECTIVE: In a group of patients with breast cancer, we aimed to analyze the methylation status of hTERT in the tumor, surrounding tissue, and circulating free deoxyribonucleic acid (cfDNA) of blood collected on the day of mastectomy and then approximately one year later. DESIGN AND SETTING: A prospective study was conducted at a university hospital in Rio de Janeiro, Brazil. METHODS: Samples were collected from 15 women with breast cancer on the day of mastectomy and approximately one year postoperatively. cfDNA was analyzed by sodium bisulfite conversion, followed by polymerase chain reaction, electrophoresis, and silver nitrate staining. RESULTS: Methylation of hTERT was detected in the tumors and surrounding tissues of all 15 patients. Five patients displayed hTERT methylation in the cfDNA from the blood of the first collection. Of the ten patients who returned for the second collection, three showed methylation. Two patients with methylation in the first collection did not display methylation in the second collection. One patient with no methylation in the first collection displayed methylation in the second collection, and one patient had a diminished level of methylation in the second collection. CONCLUSION: Only one-third of patients displayed methylation in their cfDNA, which may be related to the success of chemotherapy.

Biomarcadores evolutivos de cáncer gástrico en Nariño / Evolutionary biomarkers of gastric cancer in Nariño

Objetivo: Dilucidar el papel de la coevolución del genoma humano y de Helicobacter pylori en la patogenesis gástrica en población de Nariño-Colombia. Materiales y Métodos: Se aisló Helicobacter pylori de biopsias gástricas obtenidas de 292 pacientes con enfermedad gástrica de Nariño. El diagnóstico histológico se realizó por la clasificación de Sydney. Se incluyeron 252 cepas de H. pylori para el análisis MLST, que las asignó a poblaciones ancestrales (hpAfrica1, hpAfrica2, hpEurope, hpEAsia). Para los análisis evolutivos humanos se utilizó Immunochip y el software ESTRUCTURE para determinar proporciones de ascendencia por comparación con 712 secuencias globales de base MLST de H. pylori (http://pubmlst.org/helicobacter). Resultados: Las cepas de H. pylori en Nariño se derivan de cuatro poblaciones ancestrales: Africa (AA1), Europea (AE1 y AE2) y Asia Oriental (AEA). Los aislamientos contenían fracciones sustanciales de ancestría africana AA1 en la costa, y europea, AE2 en la región montañosa. Debido a que la población de montaña tenía un mínimo de ancestría africana del huésped, nos preguntamos si AA1 aumentaba la gravedad de las lesiones gástricas en los sujetos con baja ancestría africana. Tal escenario podría significar una coadaptación interrumpida: disrupción de la coevolución humano-H. pylori. Cuando consideramos a las 56 personas con menos del 17,6% de ancestria africana, encontramos que todas las personas que portaban H. pylori con >19,8% de ancestría africana AA1, n = 20 tenían lesiones severas. Conclusión: Las relaciones coevolutivas humano-H. pylori son biomarcadores importantes de enfermedad gástrica, y la interrupción de estas relaciones desenlazan lesiones gástricas mas avanzadas en Nariño.

Objective: To elucidate the role of the coevolution of the human genome and Helicobacter pylori in gastric pathogenesis in a population from Nariño-Colombia. Materials and Methods: Helicobacter pylori was isolated from gastric biopsies obtained from 292 patients with Nariño gastric disease. The histological diagnosis was made by the Sydney classification. 252 H. pylori isolates were included for MLST analysis, which assigned them to ancestral populations (hpAfrica1, hpAfrica2, hpEurope, hpEAsia). Immunochip was used for human evolutionary analyses. STRUCTURE software to determine ancestry proportions by comparison with 712 global H. pylori MLST base sequences (http://pubmlst.org/helicobacter). Results: The H. pylori strains in Nariño derive from four ancestral populations: African (AA1), European (AE1 and AE2), and East Asian (AEA). The isolates contained substantial fractions of AA1 African ancestry on the coast, and AE2 European ancestry in the mountains. Because the mountain population had minimal African ancestry of the host, we wondered if AA1 increased the severity of gastric lesions in subjects of low African ancestry. Such a scenario could signify disrupted coadaptation: disruption of human-H. pylori coevolution. When we considered the 56 individuals with less than 17.6% African ancestry, we found that all individuals carrying H. pylori with >19.8% AA1 African ancestry, (n = 20) had severe lesions. Conclusion: Human and H. pylori coevolutionary relationships are important biomarkers of gastric disease, and disruption of these relationships results in more advanced gastric lesions in Nariño-Colombia.

Ancestros de Helicobacter pylori de una zona de Nariño con alto riesgo de cáncer gástrico / Helicobacter pylori ancestors from an area of Nariño with high risk of gastric cancer

Objetivo: Determinar la ancestría de Helicobacter pylori aislado de pacientes provenientes de una zona de alto riesgo de cáncer gástrico del departamento de Nariño. Materiales y Métodos: Se incluyeron 16 pacientes con síntomas de dispepsia e infectados con Helicobacter pylori. Se utilizaron biopsias gástricas para el cultivo de Helicobacter pylori y subsecuente secuenciación del genoma total por Illumina MiSeq, 2x300 pb. El ensamblaje y anotación de los genomas se procedió mediante el uso de los algoritmos SPAdes y RASTtk. Las proporciones ancestrales de Helicobacter pylori se determinaron por STRUCTURE con el modelo de mezcla. Las diferencias entre estas proporciones se establecieron con las pruebas H de Kruskal Wallis y post hoc. Resultados: La estructura de la población de Helicobacter pylori deriva de cuatro poblaciones ancestrales: Ancestral Europa (AE) (61.2%), Ancestral Africa1 (AA1) (35.7%), Ancestral Este de Asia (AEA) (3%) y Ancestral Africa2 (AA2) (0.1%), siendo significativas las diferencias entre las proporciones de los ancestros de Helicobacter pylori (p<0.05). Se identificaron diferencias estadísticamente significativas entre: AA2 y AEA (p=0.022); AA2 y AA1 (p<0.05); AA2 y AE (p<0.05); AEA y AA1 (p=0.014) y AEA con AE (p<0.05), sin embargo, no se encontró diferencias significativas entre AA1 y AE (p=0.098), evaluadas por post hoc. Conclusión: Helicobacter pylori que coloniza la mucosa gástrica de una población de alto riesgo de cáncer gástrico en Nariño, deriva su acervo genético principalmente de ancestros europeos y africanos, confiriéndole a la bacteria alta capacidad competitiva asociada al desarrollo de lesiones severas en nichos gástricos amerindios.

Objective: To determine the ancestry of Helicobacter pylori isolated from patients from a high-risk area for gastric cancer in the department of Nariño. Materials and Methods: Sixteen patients with dyspepsia symptoms and infected with Helicobacter pylori were included. Gastric biopsies were used for Helicobacter pylori culture and subsequent whole genome sequencing by Illumina MiSeq, 2x300 bp. Genome assembly and annotation proceeded by using the SPAdes and RASTtk algorithms. The ancestral proportions of Helicobacter pylori were determined by STRUCTURE with the mixture model. Differences between these proportions were established with Kruskal Wallis and post hoc H-tests. Results: The population structure of Helicobacter pylori derived from four ancestral populations: Ancestral Europe (AE) (61.2%), Ancestral Africa1 (AA1) (35.7%), Ancestral East Asia (AEA) (3%) and Ancestral Africa2 (AA2) (0.1%), with differences between the proportions of Helicobacter pylori ancestors being significant (p<0.05). Statistically significant differences were identified between: AA2 and AEA (p=0.022); AA2 and AA1 (p<0.05); AA2 and AE (p<0.05); AEA and AA1 (p=0.014) and AEA with AE (p<0.05), however, no significant differences were found between AA1 and AE (p=0.098), evaluated by post hoc. Conclusion: Helicobacter pylori colonizing the gastric mucosa of a population at high risk of gastric cancer in Nariño, derives its gene pool mainly from European and African ancestors, giving the bacterium highly competitive capacity associated with the development of severe lesions in Amerindian gastric niches.

Diagnostic usefulness of triple biopsies (Skin, Muscle and Nerve) in clinically suspected cases of vasculitis in a tertiary care hospital in Gujarat

Introduction: The term vasculitis refers to a heterogeneous group of diseases, all characterized by inflammation and destruction of blood vessel walls leading to ischemic, thrombotic, and hemorrhagic damage to tissues of central and peripheral nervous system. The main indication for triple biopsy (skin, muscle and nerve) is to rule out peripheral vasculitis neuropathy. However, the drawback is that any systemic inflammatory process may show changes in a skin biopsy and hence these changes need to be interpreted with caution. The aim of this study is to establish the diagnostic yield and the usefulness of the triple biopsies in clinically suspected cases of vasculitis. Material and Methods: The present study was conducted in the Department of General Pathology, SBKS MI & RC, Vadodara over a period of one year (1/1/2022 to 31/12/2022). All the clinically suspected cases of vasculitis received at OPD were included in the study. Any case with either muscle, nerve or skin biopsy reported as inadequate were excluded from the study. Results: On evaluation the usefulness of triple biopsies for vasculitis, we found a very low diagnostic yield with only 3.3% of peripheral nerve biopsy and 0.8% of muscle and nerve biopsy showed definite vasculitis. In case of suspected peripheral/systemic vasculitic neuropathy, nerve biopsy was sufficient in the majority of case and has the diagnostic armamentarium for the evaluation of vasculitis. Conclusion: In conclusion, nerve biopsies provide the best yield for the diagnosis of vasculitis, as opposed to muscle and skin biopsies. The role of triple biopsies as a routine protocol for the evaluation of vasculitis is questionable.

Association of tumor budding in preoperative biopsies with clinicopathological characteristics and prognosis of colorectal cancer / 临床与实验病理学杂志

Purpose To explore the association of tumor budding in preoperative biopsies with the clinicopathological characteristics of colorectal cancer(CRC),and its effects on the prognosis.Methods A total of 144 preoperative biopsies and corresponding radical resection specimens of colorectal ade-nocarcinoma were collected.Tumor budding was evaluated by HE staining and EnVision immunohistochemical staining,to an-alyze the association of tumor budding with the clinicopathologi-cal characteristics and prognosis in biopsies.Results The de-tection rate of intra-tumoral budding(ITB)in biopsy specimens was 39.6%(57/144),and peritumoural budding(PTB)in surgical specimens was 64.6%(93/144);ITB was significantly correlated with PTB(r =0.510,P<0.05).The proportion of patients with lymph node metastasis,pTNM stage,differentiated degree,vascular invasion and nerve recidivism in the tumor bud-ding group of biopsies was significantly higher than that in no tumor budding group(P<0.05).Kaplan-Meier survival analy-sis showed that ITB significantly affected the overall survival and progression free survival of CRC(P<0.05).Conclusion The presence of ITB in biopsies tissue may be an important indicator of invasive behavior and poor prognosis in CRC.

Pathological Characteristics of Multiple Site Small Intestinal Biopsies in Adults With Celiac Disease / 胃肠病学

Background:Celiac disease is an autoimmune enteropathy which can present with patchy mucosal lesions.Therefore,the diagnosis of the disease requires histological evaluation of multiple site biopsies.Aims:To analyze the pathological characteristics of multiple site small intestinal biopsies in adult patients with celiac disease and provide reference for early identification and diagnosis of celiac disease.Methods:The pathological data of 22 adult patients who were newly diagnosed as having celiac disease at the People's Hospital of Xinjiang Uygur Autonomous Region from August 2019 to April 2022 were collected retrospectively.All patients were positive for serum anti-tissue transglutaminase antibody IgA,and biopsies of duodenal bulb,descending part of the duodenum and terminal ileum were obtained under endoscopy.Histological examination was performed by experienced pathologists according to the modified Marsh grading system.Results:The most common pathological grade of duodenal bulb(50.0%)and descending part of the duodenum(45.5%)was Marsh Ⅲc,while those of terminal ileum was Marsh Ⅲa(63.6%).All of the bulb biopsies,95.5%of the descending part and 72.7%of the terminal ileum biopsies showed characteristic histological changes of celiac disease.Mucosal pathology was patchy in 7 patients,of which one patient was duodenal bulb and terminal ileum involved,and 6 were duodenum involved only.Fifteen patients had diffuse small intestinal mucosal pathology involving duodenal bulb,descending part and terminal ileum,of which 4 patients showed concordant histology(the same Marsh grade in duodenal bulb,descending part and terminal ileum)and 11 patients showed discordant histology.In 18 patients(81.8%),duodenum was the only affected site or duodenum showed more serious mucosal lesions compared with terminal ileum.Conclusions:Adult celiac disease may affect the whole small intestine,and the mucosal involvement may be patchy,which highlights the importance of taking small intestinal biopsies from multiple sites repeatedly in the diagnostic work-up of celiac disease.

Mapping of SARS-CoV-2 in Waldeyer's lymphatic ring and visceral biopsies: the age and the illness duration's impact

Abstract Objective: To study the impact of age and the interval between disease diagnosis and death on the organotropism of SARS-CoV-2. Method: Patients underwent post-mortem biopsies from lungs, Waldeyer ring, heart, liver, kidneys and bone marrow between 2020-2021. SARS-CoV-2 organotropism was mapped by using molecular RT-PCR analyses for SARS-CoV2 targeting the Envelope gene (E), the RNA Polymerase Gene (RdRp), and the Nucleocapsid gene (N). Statistical and linear regression analysis was performed to study the impact of age and illness duration in SARS-CoV-2 organotropism. Results: We performed 158 postmortem biopsies in 21 patients, with a mean age of 76 years old. The mean interval between the diagnosis of the infection to the death was 23 days. The RNA of the SARS-CoV-2 was detected in 100% of lung biopsies, 76%-82% of Waldeyer's ring biopsies, 55% of heart biopsies, 40% of kidney biopsies, 33% of liver and 25% of bone marrow biopsies. Patients who died before the day 9, presented extensive visceral dissemination of SARS-CoV-2 RNA. Most of the patients older than 80 years (90%) presented visceral dissemination of SARS-CoV-2 RNA, while among younger patients, only 3/11 patients presented visceral dissemination of the virus. The relationship between "age" and "illness duration" and multitropism of the virus was statistically significant (p< 0.001). Conclusion: Disease interval and age were factors that were significantly associated with RT-PCR positive results in multiple organs. Critical COVID-19 patients have multiorganic viral dissemination in early stages. In the critical older patients, multiorganic viral dissemination is the rule. Level of evidence: 4. Case Series.

Histopathological finding of vesiculobullous lesions of skin in relation to their clinical presentation: Prospective study from a tertiary care center

Background: Vesiculobullous disorders (VBDs) are extant with diverse clinical manifestations. Vesicles and bullae are fluid-filled cavities present within or beneath the epidermis. They are autoimmune blistering disorders in which autoantibodies are directed against target antigens present in the epidermis and dermo-epidermal junction. Objective: Evaluation of the various clinicodemographic profile of patients with a pattern of distribution (subtypes) of VBDs of the skin and assess the association between clinical aspects and histological changes in vesiculobullous lesions of the skin. Materials and Methods: The study material constituted 93 cases of VBDs out of 936 skin biopsies reported over two and a half years (January 2016 to June 2018) from the tertiary care center. A detailed history of the patients was taken, and a complete physical and dermatological examination with findings including clinical diagnosis was recorded. Histopathological examination (incisional/excisional/punch biopsy) was done in each case. The clinico-demographic evaluation was done and the results were correlated with histopathological findings. Results: Vesiculobullous lesions constituted 10.06% of all skin biopsies. The majority of cases were of pemphigus vulgaris (PV) 30 (32.25%) followed by 16 (17.2%) of bullous pemphigoid. In 83 cases (89.24%) histopathology findings were consistent with clinical diagnosis. Out of 34 cases that were diagnosed clinically as PV , the histopathological study proved 30 cases (88.23%) as PV. Conclusion: Vesiculobullous lesions of the skin are a heterogeneous group of disorders. It is essential to differentiate each pattern of subtype based on clinical examination and histopathological findings. Histopathological diagnosis with clinical correlation plays a major role in arriving at the diagnosis.

Role of Immunohistochemistry and serology in subclassifying the Inflammatory Bowel Disease cases diagnosed as Inflammatory Bowel Diseases-unclassified on colonic biopsies

Background: Inflammatory bowel diseases (IBDs) mainly consist of Crohn's Disease (CD) and Ulcerative Colitis (UC). These two categories have overlapping histopathological features and sometimes it is difficult to diagnose them into distinct category and such biopsies are categorised as Inflammatory Bowel Disease (IBD-U). Recently, there has been an increase in interest to discover new biomarkers of IBD to differentiate UC and CD and predict their prognosis. Method: In the present study, 273 non-neoplastic colonic biopsies with clinicoendoscopic features of IBD were studied and categorized into UC (88; 32.3%) and CD (03; 1.1%) but a major chunk remained in category of IBD-U (182; 66.6%). 161 (58.9%) of these biopsies were then subjected to IHC for RB protein and ?-catenin and Serology for pANCA and ASCA was done in only 85 (31.13%) of these selected cases for identification of UC and CD on colonic biopsies. Result: 161 biopsies that were subjected to IHC analysis included 57 cases of UC, 03 cases of CD, and rest 101 cases of IBD-U. Out of 101 cases of IBD-U, 87 (86.13%) cases were reclassified as UC (61; 60.3%) and CD (14; 13.86%) on the basis of results of IHC and Serology. Conclusion: The two major tools IHC for ?-catenin and RB protein and the assay of serum ASCA and p-ANCA along with proper history and clinical presentation can act as a good adjunct to conventional H and E in subclassifying cases of IBD-U into UC and CD.

Forms of non-neoplastic colonic biopsies: Histopathological Interpretation of five years observation.

Colorectal troubles are frequently common in medical practice ranging from mild nonspecific complaints to serious suffering. Colonic mucosal biopsies are considering one of the diagnostic tool in the evaluation of patients with colorectal pathologies. The objectives of this study are focusing for interpretation various spectrum of colonoscopic biopsies and to provide a guide to the plan of management strategy. This retrospective study was including 250 colonoscopic biopsies collected during the from December 2015 through January 2020. Among them 160 cases were of the Non-Inflammatory Bowel Disease Colitis (NIBDC) entities whereas, remaining 90 cases were Inflammatory Bowel Disease (IBD). Among the first one, 100 (40%) cases were Non-specific colitis, 13 (5.2%) bacterial colitis, 2 (0.8%) collagenous colitis, 15 (6%) hyperplastic polyp, 5 (2%) Peutz-Jeuger's polyps, 5 (2%) solitary rectal ulcer, 4 (1.6%) eosinophilic colitis, 3 (1.2%) Juvenile polyp, and 3 (1.2%) were melanosis coli, and remaining 10 (4%) cases were unremarkable. In regard to the IBD, 60 cases (24%) were ulcerative colitis and 30 (12%) Crohn disease. Majority of colonic troubles are linked to non-specific pathologies whereas, IBD is considering the second detectable colonic lesions in our study.

Analysis of the detection of non-caseating granuloma under endoscopy in 199 patients with Crohn′s disease / 中华消化杂志

Objective:To explore the detection rate of non-caseating granuloma under endoscopy in patients with Crohn′s disease and its influencing factors, in order to improve the pathological diagnosis rate of Crohn′s disease.Methods:From July 2016 to April 2021, at the First Affiliated Hospital of Soochow University, 199 patients who met the clinical diagnostic criteria for Crohn′s disease and underwent endoscopic biopsy were collected. The detection rates of non-caseating granulomas in all patients with Crohn′s disease, in different types (primary and recurrent) and whether the biopsy site included the colon were analyzed. According to whether non-caseating granulomas were detected by endoscopic biopsy, the patients were divided into the detected group and the undetected group. The clinical data of the two groups of patients were compared, which included gender, age, course of disease, body mass index, smoking status, clinical manifestations (abdominal pain, diarrhea, gastrointestinal bleeding, perianal lesions, weight loss, fever, intestinal obstruction), therapeutic medication (5-aminosalicylic acid, immunosuppressants, glucocorticoid, biological agents, exclusive enteral nutrition), history of bowel surgery, laboratory examination results (hemoglobin, platelet count, neutrophil count, C-reactive protein, erythrocyte sedimentation rate, albumin), endoscopic manifestation (ulcer, fistula, stricture), simplified Crohn′s disease activity index (CDAI), total number of biopsy samples, and site of biopsy. Chi-square test, continuity correction chi-square test, Mann-Whitney U test and Fisher exact test were used for statistical analysis, and logistic regression analysis was used to analyzed the influencing factors of detection of non-caseating granulomas under endoscopy. Results:Among the 199 patients with Crohn′s disease, 67 cases were detected with non-caseating granuloma (detected group), and the overall detection rate was 33.7% (67/199); 132 cases were not detected with non-caseating granuloma (undetected group). The detection rate of non-caseating granulomas in patients with primary Crohn′s disease was higher than that of recurrent patients (39.9%, 59/148 vs. 15.7%, 8/51), and the detection rate of non-caseating granulomas in patients with Crohn′s disease whose biopsy site included the colon was higher than that of patients whose biopsy site did not include colon (64.1%, 25/39 vs. 26.3%, 42/160), and the differences were statistically significant ( χ2=9.93 and 20.12 , P=0.002 and <0.001). The age of patients in the detected group was younger than that of the undetected group; the course of disease of the detected group was shorter than that of the undetected group; the proportions of patients with abdominal pain and history of biological treatment in the detected group were lower than those of the undetected group; the simplified CDAI score of the detected group was higher than that of the undetected group; and the total number of biopsy samples of the detected group was more than that of the undetected group (30.0 years old (25.0 years old, 37.00 years old) vs. 32.0 years old (28.0 years old, 41.0 years old); 1.0 year (0.0 year, 3.0 years) vs. 2.0 years (0.0 year, 5.0 years), 61.2%, 41/67 vs. 75.8%, 100/132; 0, 0/67 vs. 10.6%, 14/132; 5.00 (2.00, 7.00) vs. 4.00 (2.00, 6.00); 10 (8, 12) vs. 6 (3, 9)), and the differences were statistically significant ( Z=-2.29, -1.99, χ2=4.56, corrected χ2=6.11, Z=-2.05, -5.64, all P<0.05). The case number of biopsy location in terminal ileum, colon, ileocolon, upper gastrointestinal tract, terminal ileum+ upper gastrointestinal tract, ileocolon+ upper gastrointestinal tract in the detected group was 36, 4, 18, 1, 5 and 3, respectively, compared with those of undetected group (94, 4, 8, 11, 13 and 2), the difference was statistically significant (Fisher′s exact test, P<0.001). The results of multivariate logistic regression analysis suggested that the total number of biopsy samples, whether the biopsy site included the colon and disease type were independent influencing factors for the detection of non-caseating granulomas under endoscopy in patients with Crohn′s disease (regression coefficients=0.157, 0.979 and -0.960, OR=1.171, 2.662 and 0.383; 95% confidence interval 1.067 to 1.284, 1.140 to 6.214, 0.158 to 0.929; P=0.001, 0.024 and 0.034). Conclusions:For endoscopic examination in patients with suspected Crohn′s disease, the total number of biopsy samles should be increased as much as possible, and biopsy should be performed at the colonic lesions, in order to improve the detection rate of non-caseating granulomas under endoscopy thereby providing more pathological evidence for the diagnosis of Crohn′s disease.

Histopathological pattern of Orbito-Ocular Lesions, a retrospective hospital-based study spanning 15 years

Background: Many previous studies on orbito-ocular lesions are skewed in favour of the neoplastic lesions in general and the malignant lesions in particular. This, therefore, creates a vacuum on the spectrum of these lesions, thus may result in problematic diagnostic bias by the ophthalmologist and pathologist. Objective: To give the spectrum and relative frequencies of orbito-ocular biopsies and by extension orbito-ocular lesions/diseases at the University of Benin Teaching Hospital (UBTH). Materials and Methods: A retrospective descriptive study of all cases of orbito-ocular biopsies with histopathologic diagnosis. Results: There were 236 orbito-ocular biopsies. The male to female ratio was slightly in favour of the females. Orbito-ocular biopsies had a wide age range that spanned from the 1st to 10th decade, mean age in the 3rd decade (20-29years) and a peak age in the 1st decade (0-9 years). The neoplastic lesions were the prevalent indication for orbito-ocular biopsies (63.72%) while the conjunctiva (58.10%) was the most common site for orbito-ocular biopsies. Conclusion: This study noted a wide array of orbito-ocular lesions for which biopsies were done for histopathological diagnosis. This we hope will in no small measure increase the diagnostic precision of the ophthalmologist and the pathologists in our own environment

Guillain-Barre syndrome related to COVID-19: muscle and nerve biopsy findings

BACKGROUND: the involvement of the peripheral nervous system (PNS) in COVID-19 is rare and, to date, morphological aspects from muscle and nerve biopsies have not been reported. Here, we describe a case of Guillain-Barré Syndrome (GBS) related to COVID-19 and demonstrate findings from peripheral nerve and skeletal muscle biopsies. A 79-year-old man presented with progressive weakness in both legs over one-week, evolving to both arms and urinary retention within 6 days. Four days earlier, he had a cough, febrile sensation and mild respiratory discomfort. On admission, his was afebrile, and without respiratory distress. A neurological examination disclosed asymmetric proximal weakness, diminished reflexes and no sensitive abnormalities. Three days later, the patient presented with bilateral facial weakness and proximal muscle strength worsened. Deep tendon reflexes and plantar responses were absent. Both superficial and profound sensitivity were decreased. From this point, oxygen saturation worsened, and the patient was placed on mechanical ventilation. CSF testing revealed one cell and protein 185 mg/dl. A chest CT showed the presence of ground-glass opacities and RT-PCR for SARS-CoV-2 was positive. The muscle biopsy revealed moderate neuromyopathic findings with positive expression for MHC-class I, C5b9, CD8 and CD68. The nerve biopsy showed inflammatory infiltrates predominantly with endoneurial compound formed by CD45 and CD68. The patient was treated with Oseltamivir for 9 days followed by IVIG for 5 days and died three days later of septic shock. DISCUSSION: this is the first documented case of GBS associated with COVID-19 with a muscle and nerve anatomopathological study. A systematic review about neurological complications caused by COVID-19 described 11 patients with GBS. The morphological features reported in our patient showed signs of involvement of the immune system, suggesting that direct viral invasion could have played a role in the pathogenesis of peripheral nerve injury. Hereafter, further research will be necessary to understand the triggers for these cells migrating into the peripheral nerve.

INTRODUÇÃO: O envolvimento do sistema nervoso periférico (SNP) na COVID-19 é raro e, até o momento, os aspectos morfológicos de biópsias de músculo e nervo não foram relatados. Descrevemos um caso de Síndrome de Guillain-Barré (SGB) na vigência de COVID-19 destacando os achados na biopsia de músculo e nervo. Um homem de 79 anos apresentou fraqueza progressiva em ambas as pernas ao longo de uma semana, evoluindo para ambos os braços e retenção urinária em 6 dias. Quatro dias antes, apresentou tosse, sensação febril e leve desconforto respiratório. Na admissão, apresentava-se afebril e sem alteração respiratória. O exame neurológico mostrou fraqueza proximal assimétrica, reflexos diminuídos e sensibilidade preservada. Três dias após, o paciente evoluiu com fraqueza facial bilateral e piora da força muscular proximal. Reflexos tendinosos profundos e cutâneo plantar ausentes bilateralmente. A sensibilidade superficial e profunda estavam diminuídas. Evoluiu com piora na saturação de oxigênio sendo colocado sob ventilação mecânica. O exame de liquor revelou uma célula e aumento de proteína (185 mg / dl). A TC de tórax revelou a presença de opacidades em vidro fosco e o RT-PCR para SARS-CoV-2 foi positivo. A biópsia muscular mostrou achados neuromiopáticos moderados com imunoexpressão positiva para MHC classe I, C5b9, CD8 e CD68. A biópsia de nervo revelou infiltrado inflamatório inflamatórios predominantemente endoneural composto por CD45 e CD68. O paciente foi tratado com Oseltamivir por 9 dias seguido de IVIG por 5 dias indo a óbito após três dias por choque séptico. DISCUSSÃO: Este é o primeiro caso documentado de SGB associada a COVID-19 com estudo anatomopatológico de músculo e nervo. Uma revisão sistemática de complicações neurológicas associadas à COVID-19 descreveu 11 pacientes com SGB. As características morfológicas em nosso paciente mostrando sinais de envolvimento do sistema imunológico sugere que a invasão viral direta pode ter colaborado no processo patogênico da lesão neuromuscular. A partir daí, mais pesquisas serão necessárias para entender os gatilhos para essas células migrarem para o nervo periférico.

Elastografía cuantitativa en la evaluación de nódulos tiroideos / Quantitative Elastography in the Evaluation of Thyroid Nodules

Resumen: Objetivo. Evaluar retrospectivamente la capacidad diagnóstica de la elastografía cuantitativa para determinar la posibilidad de malignidad o benignidad de los nódulos tiroideos benignos y malignos, y determinar su utilidad para así decidir qué nódulos deberán ser sometidos a punción aspirativa con aguja fina (PAAF). Pacientes y métodos. Se analizaron 203 nódulos tiroideos de 195 pacientes remitidos por el Servicio de Endocrinología para estudio citológico durante el año 2018. A todos ellos se les realizó ecografía convencional, elastografía cuantitativa y PAAF. Se realizó un análisis estadístico mediante regresión logística, que pone en relación la probabilidad de que un nódulo sea sospecho de malignidad y el valor de la elasticidad medido en kilopascales (kPa) y el ratio elastográfico. Resultados. Existe una relación significativa y positiva entre el resultado citológico de Bethesda V/VI y los kPas/ratio elastográfico. Se recomienda realizar PAAF a aquellos nódulos con valores superiores a 25kPa y/o ratio elastográfico superior a 1,5. Conclusión. La elastografía cuantitativa es una herramienta útil que, junto a otros parámetros ecográficos, ayudaría a predecir o sospechar la malignidad de un nódulo tiroideo y a una mejor selección para la PAAF.

Abstract: Objective. To retrospectively assess the diagnostic capacity of quantitative elastography to determine the odds between benign and malignant thyroid nodules, and determine its usefulness in deciding which nodules should be subjected to fine needle aspiration puncture (FNA). Patients and methods. 203 thyroid nodules from 195 patients referred by the Endocrinology Service for cytological study during the year 2018 were analyzed. All of them underwent conventional ultrasound, quantitative elastography and FNA. A statistical analysis was performed using logistic regression that relates the probability that a nodule is suspected of malignancy and the elasticity value measured inkilopascals (kPa) and the elastographic ratio. Results. There is a significant and positive relationship between the cytological result of Bethesda V / VI and the kPas / elastographic ratio. FNA is recommended for those nodules with values greater than 25kPa and / or elastographic ratio greater than 1.5. Conclusion. Quantitative elastography is a useful tool that, together with other ultrasound parameters, would help to predict the malignancy of a thyroid nodule and to better select for FNA.

Developing a coordinate-based strategy to support cognitive targeted prostate biopsies and correlative spatial-histopathological outcome analysis / 亚洲男科学杂志(英文版)

Lack of investment for magnetic resonance (MR) fusion systems is an obstacle to deliver targeted prostate biopsies within the prostate cancer diagnostic pathway. We developed a coordinate-based method to support cognitive targeted prostate biopsies and then performed an audit on cancer detection and the location of lesions. In each patient, the prostate is considered as two separate hemiprostates, and each hemiprostate is divided into 4 × 4 × 4 units. Each unit is therefore defined by a three-dimensional coordinate. We prospectively applied our coordinates approach to target 106 prostatic lesions in 93 men. Among 45 (of 106; 42.5%) lesions positive for cancer, 27 lesions (60.0%) harbored clinically significant disease. PSA density was significantly higher in patients with proven cancer (median: 0.264 ng ml

Radical prostatectomy on a 66-year-old patient with a positive 18F-PSMA uptake: Potential application for multiple negative prostate biopsy results

@#The decision to proceed with radical prostatectomy has to be supported with biopsy-proven prostate cancer. However, when a patient has persistently multiple negative prostate biopsies and a high PSA, a serious diagnostic and therapeutic dilemma arises. The PIRADS score generated by the multiparametric-MRI of the prostate provides a guide for a template biopsy using MRI-ultrasound fusion technology, with the hope of minimizing a false negative result. Fluorine-18 Prostate-Specific Membrane Antigen (18F-PSMA) PET CT scan, on the other hand, is used mainly for staging prostate cancer after biochemical recurrence. The use of 18F-PSMA PET CT in the primary clinical diagnosis of prostate cancer has never been reported.The authors performed radical prostatectomy on a 66-year-old HIV-positive male with suspicious lesion on 18F-PSMA, PIRADS 5 on mp-MRI, and a persistently elevated PSA >100 despite multiple negative biopsies. The final histopathological analysis confirmed the presence of adenocarcinoma of the prostate, Gleason 7 (3+4), with negative margins. There were no intraoperative complications, and the patient was discharged in good condition. On follow-up, he had a nadir PSA of 0.058 ng/ml, has partial incontinence, and decreased erectile function and was advised phosphodiesterase inhibitors. 18F-PSMA may be utilized in the decision process for patients who are highly suspected with malignancy but have no preoperatively biopsy-proven cancer after multiple negative biopsies.

The common histopathological findings of colon biopsies in Northern Saudi Arabia

Background: Colorectal cancer is considered as the most prevalent cancer among men and the third mostfrequent cancer among women in Saudi Arabia. Consequently, we aimed to assess the commonhistopathological findings of colon biopsies in Northern Saudi Arabia. Methodology: This study hasinvestigated the histopathological diagnosis of 88 patients subjected for colon and small intestine biopsies, theirages ranging from 18 to 99 years with a mean age of 48 years old at the Department of Pathology at KingKhalid Hospital, Hail, Northern Saudi Arabia. Results: Out of the 88 patients, 53(60.2%) were males and35(39.8%) were females. Diagnoses were reached in 77/88(87.5%) of the patients and could not be ascertainedin 11/88(12.5%). Adenocarcinoma was diagnosed in 10/77(13%) of the patients (9/10(90%) in colon-site and1/9(10%) in the small intestine. Conclusion: Colorectal precancerous and cancerous lesions are relativelyprevalent among patients referred to colorectal diagnostic biopsy. There is a substantial percentage ofinflammatory bowel cases among those referred to colorectal biopsies in Saudi Arabia.

Development status and clinical applications of precision detection technology in the times of precision oncology / 中国肿瘤生物治疗杂志

@#Precision detection techniques have promoted the development of individualized diagnosis and treatment of tumors in the era of precision medicine. At the same time, clinical demands of precision treatments have further driven the development and application of precision detection techniques. In recent years, precision medical detection techniques realized rapid transformations from low-throughput to high-throughput genomic sequencing, from tissue biopsies to liquid biopsies, and from multicell promiscuous detection to single cell precision sequencing. All these changes have promoted the emergence and development of new technologies, new targets, and new drugs in the era of precision oncology medicine. In the future, multi-dimensional combined detection could help to improve the accuracy of precision medicine; ctDNA methylation detection analysis could broaden the research field of precision medicine; and the transformation of clinical trial design could also contribute to promote the in-depth development of precision medicine.

Tumor filodes de la mama: experiencia en el diagnóstico, tratamiento y seguimiento de 28 casos en Colombia / Phyllodes tumor of the breast: experience in the diagnosis, treatment and follow-up of 28 cases in Colombia

Resumen: OBJETIVO: Describir la experiencia en el diagnóstico, tratamiento y seguimiento de pacientes con tumor filodes que consultaron en dos instituciones de Bogotá, en un periodo de 6 años. MATERIALES Y MÉTODOS: Estudio descriptivo, de serie de casos. Se revisaron las historias clínicas y los reportes de patología quirúrgica de pacientes con diagnóstico de tumor filodes que asistieron a la consulta de Mastología del Hospital de San José y Hospital Infantil Universitario de San José entre los meses de enero de 2013 a junio de 2019. Se analizaron los estudios imagenológicos, biopsias preoperatorias, tratamiento quirúrgico, reporte final de Patología y el seguimiento posterior al tratamiento. Toda la información se guardó en una base de datos con las características sociodemográficas y clínicas de interés. RESULTADOS: Se reportaron 15 de 28 casos benignos, 7 de 28 malignos y 6 de 28 fronterizos; la mediana de edad fue de 49.3 años (rango intercuartil: 43.5 -57), la biopsia trucut identificó a 18 de 28 casos con tumor filodes. Los estudios ecográficos se reportaron como BI-RADS 4 en 18 de 28 pacientes. El tratamiento quirúrgico fue cuadrantectomía y mastectomía, según el tamaño de la lesión. No se reportaron muertes. CONCLUSIONES: El tumor filodes es de crecimiento rápido, baja incidencia, frecuente en mujeres entre la quinta y sexta décadas de la vida, aunque se registran casos en edades extremas (15 y 74 años). El síntoma principal es una masa palpable; en estudios de imágenes se manifiesta como lesión sugerente de malignidad (BI-RADS 4). El tratamiento quirúrgico es la base de la conducta terapéutica.

Abstract: OBJECTIVE: Describe the experience of diagnosis, treatment and follow-up of patients with phyllodes tumor who consulted in two institutions in Bogotá, in a period of 6 years. MATERIALS AND METHODS: A descriptive case series study was carried out, where clinical histories and reports of surgical pathology of patients with a diagnosis of PT who attended a mastology consultation at the San José Hospital and San José University Children's Hospital in January were reviewed. from 2013 to June 2019. Imaging studies, preoperative biopsies, surgical management, final pathology report and post-treatment follow-up were analyzed. A database with sociodemographic and clinical characteristics of interest was tabulated. RESULTS: 15 of 28 benign cases, 7 of 28 malignant cases and 6 of 28 borderline cases were reported, the median age was 49.3 years (RIC 43.5 -57), Trucut biopsy identified 18/28 of phyllodes tumor. Ultrasound studies were reported as BIRADS 4 in 18/28. The surgical management was quadrantectomy and mastectomy according to the size of the lesion. No deaths were reported. CONCLUSIONS: Phyllodes tumor is a tumor of rapid growth, low incidence, frequent in the fifth and sixth decade of life, however, cases are recorded at extreme ages (15-74 years). Its main symptom is palpable mass and in imaging studies it manifests itself as suggestive lesions of malignancy (BIRADS 4). Surgical management is considered as the treatment pillar.

Diagnóstico genético preimplantacional no invasivo; datos preliminares en México / Non-invasive preimplantation genetic diagnosis; preliminary data in Mexico

Resumen: OBJETIVO: Analizar las tasas de concordancia, falsos positivos y negativos entre el ADN embrionario circulante en medio de cultivo y su relación con los reportes de la biopsia de trofoectodermo. MATERIALES Y MÉTODOS: Estudio observacional, prospectivo y comparativo, llevado a cabo en el Centro de Reproducción Arcos Nascere en noviembre 2018. Criterios: de inclusión: parejas en esquema de fertilización in vitro, con diagnóstico genético preimplantacional de aneuploidias. Criterios de exclusión: pacientes con anomalías estructurales o enfermedades monogénicas. Criterio de eliminación: blastocistos con eclosión asistida. Variables de respuesta: tasa de concordancia, falsos positivos y negativos entre las biopsias de trofoectodermo y los medios de cultivo. El análisis estadístico se realizó con SPSS 25.0, con pruebas t de Student y χ2 con valor de p < 0.05 significativa. RESULTADOS: Se analizaron 20 blastocistos de 5 parejas y se obtuvieron resultados informativos de 17 (amplificación global exitosa); 70% en día 5 y 100% en día 6. La tasa general de concordancia entre las biopsias de trofoectodermo y los medios de cultivo fue de 68.7% (42.8% en día 5 y 88.8% en día 6). En cuanto a las discrepancias, solo se observaron 2 falsos negativos en los medios de cultivo vs la biopsia de trofoectodermo (14.2% en día 5 y 11.11% en día 6); hubo 3 casos de falsos positivos (la mitad en día 5 y ninguno en día 6-7). CONCLUSIONES: Con la prueba genética no invasiva de aneuploidias se alcanzaron altas tasas de concordancia, sobre todo en embriones en día 6.

Abstract: OBJECTIVE: Analyze the concordance, false positive and false negative rates between circulating free DNA of the culture media compared to the results of the trophectoderm biopsy. MATERIALS AND METHODS: Observational, prospective and comparative study, conducted at Arcos Reproduction Center S.C. Nascere in november 2018. Couples with indication of preimplantation genetic diagnosis of aneuploidies undergoing In vitro Fertilization were included; carriers of structural anomalies or monogenic diseases were excluded and blastocysts with assisted hatching were eliminated. The response variables were the concordance, false positives and false negatives rates between trophoctoctoderm biopsies and culture media. Statistical analysis was performed with SPSS 25.0, using t-Student and chi-square tests with a value of p <0.05 significant. RESULTS: Informative results were obtained in 17 of the 20 culture media (85% successful global amplification); 70% on day 5 and 100% on day 6. The general concordance rate between trophectoderm biopsies and culture media was 68.7% (42.8% on day 5 and 88.8% on day 6). Regarding discrepancies, only 2 false negatives were observed in the culture media compared to the trophectoderm biopsy (14.2% on day 5 and 11.1% on day 6). There were 3 cases false positives (42.8% on day 5 and 0% on day 6). CONCLUSIONS: High rates of concordance were reached with the non-invasive genetic aneuploidy test, mainly in embryos on day 6.