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1.
Pathology ; 56(2): 205-213, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38238239

RESUMO

Tumours of the gastrointestinal tract represent nearly a quarter of all newly diagnosed tumours diagnosed in 2019. Various treatment modalities for gastrointestinal cancers exist, some of which may be guided by biomarkers. Biomarkers act as gauges of either normal or pathogenic processes or responses to an exposure or intervention. They come in many forms. This review explores established and potential molecular/immunohistochemical (IHC) predictive and prognostic biomarkers of the gastrointestinal tract.


Assuntos
Biomarcadores Tumorais , Neoplasias Gastrointestinais , Humanos , Prognóstico , Neoplasias Gastrointestinais/diagnóstico , Neoplasias Gastrointestinais/patologia
2.
Case Rep Gastrointest Med ; 2023: 4248128, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37663588

RESUMO

Gastrointestinal stromal tumours (GISTs) are the most common mesenchymal tumours of the GI tract, usually found in the stomach, jejunum, and ileum. Typically, they are KIT or PDGFR-mutated, allowing for targetable treatments with tyrosine kinase inhibitors such as imatinib. Here, we present two KRAS-mutated wild-type gastrointestinal tumours (GISTs). Both cases occurred in the small bowel of females. Immunohistochemical studies on both tumours showed KIT and DOG-1 positivity, with SDHB retained. Molecular analysis revealed a KRAS G12D mutation and a KRAS G13D mutation, respectively. Wild-type GISTs are extremely uncommon. They typically occur in the stomach or the small bowel. KRAS is one of the genes implicated in this subset of GIST, with KRAS G12D being the most frequently encountered mutation. GIST KRAS mutations can arise alone or in conjunction with KIT, PDFRA, or BRAF mutations. Identification of these rare molecular subtypes is clinically important due to their resistance to imatinib therapy.

4.
Lab Invest ; 103(7): 100145, 2023 07.
Artigo em Inglês | MEDLINE | ID: mdl-37004911

RESUMO

The goal of this study was to develop a methylation-based droplet digital PCR to separate 2 cancer classes that do not have sensitive and specific immunohistochemical stains: gastric/esophageal and pancreatic adenocarcinomas. The assay used methylation-independent primers and methylation-dependent probes to assess a single differentially methylated CpG site; analyses of array data from The Cancer Genome Atlas network showed that high methylation at the cg06118999 probe supports the presence of cells originating from the stomach or esophagus (eg, as in gastric metastasis), whereas low methylation suggests that these cells are rare to absent (eg, pancreatic metastasis). On validation using formalin-fixed paraffin-embedded primary and metastatic samples from our institution, methylation-based droplet digital PCR targeting the corresponding CpG dinucleotide generated evaluable data for 60 of the 62 samples (97%) and correctly classified 50 of the 60 evaluable cases (83.3%), mostly adenocarcinomas from the stomach or pancreas. This ddPCR was created to be easy-to-interpret, rapid, inexpensive, and compatible with existing platforms at many clinical laboratories. We suggest that similarly accessible PCRs could be developed for other differentials in pathology that do not have sensitive and specific immunohistochemical stains.


Assuntos
Adenocarcinoma , Neoplasias Pancreáticas , Neoplasias Gástricas , Humanos , Adenocarcinoma/diagnóstico , Adenocarcinoma/genética , Neoplasias Pancreáticas/diagnóstico , Neoplasias Pancreáticas/genética , Metilação de DNA , Reação em Cadeia da Polimerase , Neoplasias Gástricas/diagnóstico , Neoplasias Gástricas/genética , Esôfago , Neoplasias Pancreáticas
5.
Neurol Neurochir Pol ; 57(1): 111-120, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36799525

RESUMO

INTRODUCTION: Previous studies on the prognostic role of sex in post-COVID-associated brain fog have yielded divergent results. Moreover, limited evidence exists regarding the evolution of brain fog symptoms over time, especially in ambulatory patients and separately for women and men. Therefore, the aim of the current study was to assess brain fog symptoms in nonhospitalised patients with COVID-19, according to their sex. MATERIAL AND METHODS: We created a neuropsychological questionnaire including eight questions on the presence of brain fog symptoms in the following four time periods: before COVID-19, and 0-4, 4-12, and > 12 weeks post-infection. The validity and reliability of the questionnaire were assessed. In this cross-sectional study, questionnaires were filled out anonymously and retrospectively once only by patients or through a survey link posted online. Included were patients ≥ 18 years, with > 3 months since the SARS-CoV-2 infection onset confirmed by RT-PCR from a nasopharyngeal swab. RESULTS: The study included 303 patients (79.53% women, 47.52% medical personnel). Median time between COVID-19 onset and questionnaire completion was 208 (IQR 161-248) days. Women, compared to men, reported a higher prevalence of problems with writing, reading, and counting (< 4 weeks, OR 3.05, 95% CI: 1.38-6.72; 4-12 weeks, OR 2.51, 95% CI: 1.02-6.14; > 12 weeks, OR 3.74, 95% CI: 1.12-12.56) and thoughts communication (< 4 weeks, OR 2.53, 95% CI: 1.41-4.54; 4-12 weeks, OR 3.74, 95% CI: 1.93-7.24; > 12 weeks, OR 2.00, 95% CI: 1.01-3.99). The difference between the two sexes in answering questions in an understandable/unambiguous manner was statistically significant between four and 12 weeks after infection (OR 2.63, 95% CI: 1.36-5.10), while a sex difference in recalling new information was found below 12 weeks (OR 2.54, 95% CI: 1.44-4.48 and OR 2.43, 95% CI: 1.37-4.31 for < 4 and 4-12 weeks, respectively). No sex differences in reporting problems with multitasking, remembering information from the past, determining the current date, or field orientation were noted. CONCLUSIONS: Non-hospitalised women and men retrospectively report a different course of COVID-19-associated brain fog.


Assuntos
COVID-19 , Masculino , Humanos , Feminino , COVID-19/epidemiologia , SARS-CoV-2 , Estudos Retrospectivos , Estudos Transversais , Reprodutibilidade dos Testes , Medidas de Resultados Relatados pelo Paciente , Encéfalo
6.
J Clin Pathol ; 76(2): 73-75, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-36600573

RESUMO

The partner and localiser of BRCA2 (PALB2) gene, located on chromosome 16, functions as a tumour suppressor that plays a critical role in homologous recombination repair after DNA double-strand breaks. It encodes proteins involved in the BRCA2 and BRCA1, and RAD51 pathways. Heterozygous germline mutations in PALB2 have been implicated in the development of breast, pancreatic and ovarian cancers. Whereas biallelic mutations of PALB2 have been associated with Fanconi anaaemia. Currently, 604 distinct PALB2 variants have been discovered. However, only 140 variants are thought to be pathogenic and approximately 400 are variants of unknown significance. Further studies are needed before the presence of PLAB2 mutations can be implemented as a routine clinical biomarker.


Assuntos
Neoplasias da Mama , Proteínas Supressoras de Tumor , Feminino , Humanos , Proteínas Supressoras de Tumor/genética , Proteínas Supressoras de Tumor/metabolismo , Proteínas Nucleares/genética , Proteína do Grupo de Complementação N da Anemia de Fanconi/genética , Proteína do Grupo de Complementação N da Anemia de Fanconi/metabolismo , Proteína BRCA2/genética , Proteína BRCA2/metabolismo , Proteína BRCA1/genética , Reparo do DNA , Mutação , Neoplasias da Mama/genética , Predisposição Genética para Doença
7.
Front Neurol ; 13: 913283, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35775049

RESUMO

Background and Objectives: Since vaccination against COVID-19 is available for over a year and the population of immunized individuals with autoimmune disorders is higher than several months before, an evaluation of safety and registered adverse events can be made. We conducted a large study of side effects following the COVID-19 vaccine among patients with multiple (MS) sclerosis treated with disease-modifying therapies (DMTs) and analyzed factors predisposing for particular adverse events. Methods: We gathered data of individuals with MS treated with DMTs from 19 Polish MS Centers, who reported at least one adverse event following COVID-19 vaccination. The information was obtained by neurologists using a questionnaire. The same questionnaire was used at all MS Centers. To assess the relevance of reported adverse events, we used Fisher's exact test, t-test, and U-Menn-Whutney test. Results: A total of 1,668 patients with MS and reports of adverse events after COVID-19 vaccination were finally included in the study. Besides one case marked as "red flag", all adverse events were classified as mild. Pain at the injection site was the most common adverse event, with a greater frequency after the first dose. Pain at the injection site was significantly more frequent after the first dose among individuals with a lower disability (EDSS ≤2). The reported adverse events following immunization did not differ over sex. According to age, pain at the injection site was more common among individuals between 30 and 40 years old, only after the first vaccination dose. None of the DMTs predisposed for particular side effects. Conclusions: According to our findings, vaccination against COVID-19 among patients with MS treated with DMTs is safe. Our study can contribute to reducing hesitancy toward vaccination among patients with MS.

8.
Transplant Proc ; 54(4): 1109-1114, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-35654636

RESUMO

BACKGROUND: Lung transplantation (LTx) is the only effective method of treatment for patients with end-stage lung diseases; LTx prolongs and increases the quality of life (QoL). An important aspect of QoL that changes in the course of severe diseases is the quality of sex life. This aspect is yet to be discussed in relationship to LTx. We aim to compare patients' quality of sex life at the qualification process with patients' who underwent LTx. METHODS: The studied group consisted of 100 patients (24 women before and 16 after LTx, 39 men before and 21 after LTX) who were admitted to the lung transplantology department for qualification or to control the function after LTx. To assess the patients' quality of sex life, we used The Changes in Sexual Functioning Questionnaire (CSFQ) and World Health Organization (WHO) QoL-BREF. To assess lung function, patients underwent a 6-Minute-Walk-Test (6MWT). RESULTS: Patients after LTx obtained higher results-compared to patients qualified for LTx-in the WHO QoL-BREF in every domain (somatic, psychological, social, and environment). Men after LTx got more points in every domain and better total score (53 ± 5.62 vs 44.23 ± 10.28 point; P < .05) in CSFQ. Women before and after LTx obtained comparable results in CSFQ. Results of 6-Minute-Walk-Test were better among patients after LTx than in qualified patients (523.62 ± 95.71 vs 333.14 ± 145.38 and 524.12 ± 56.17 vs 317.20 ± 141.6, respectively for men and women). CONCLUSIONS: Patients after LTx show better pulmonary function and quality of sex life than qualified. Preliminary results encourage us to conduct research on a larger group.


Assuntos
Transplante de Pulmão , Qualidade de Vida , Feminino , Humanos , Pulmão , Transplante de Pulmão/efeitos adversos , Transplante de Pulmão/métodos , Masculino , Inquéritos e Questionários , Teste de Caminhada
9.
J Clin Pathol ; 75(9): 577-580, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-35738886

RESUMO

The ERG gene belongs to the erythroblastosis transformation specific family of transcription factors and encodes for the transcription regulator protein ERG. It is located on chromosome 22q22 and is a nuclear transcription factor. In normal physiology, ERG protein is expressed in endothelial cells and is involved in processes including, but not limited to, angiogenesis and haematopoiesis. Of diagnostic value in clinical practice, ERG immunohistochemistry is a useful marker of endothelial differentiation for both benign and malignant vascular lesions. It is also reliable for identifying ERG gene translocated malignancies such as EWS/FUS::ERG Ewing's sarcoma and TMPSSR2::ERG prostatic carcinoma.


Assuntos
Células Endoteliais , Sarcoma de Ewing , Células Endoteliais/metabolismo , Humanos , Proteínas de Fusão Oncogênica/genética , Proteínas de Fusão Oncogênica/metabolismo , Proteína EWS de Ligação a RNA/metabolismo , Sarcoma de Ewing/genética , Sarcoma de Ewing/patologia , Fatores de Transcrição/genética , Regulador Transcricional ERG/genética , Regulador Transcricional ERG/metabolismo
10.
Front Hum Neurosci ; 16: 852981, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35620154

RESUMO

Background: Fatigue is one of the most common symptoms of multiple sclerosis (MS), significantly affecting the functioning of the patients. However, the neural underpinnings of physical and mental fatigue in MS are still vague. The aim of our study was to investigate the functional architecture of resting-state networks associated with fatigue in patients with MS. Methods: The sum of 107 high-functioning patients underwent a resting-state scanning session and filled out the 9-item Fatigue Severity Scale (FSS). Based on the FSS score, we identified patients with different levels of fatigue using the cluster analysis. The low-fatigue group consisted of n = 53 subjects, while the high-fatigue group n = 48. The neuroimaging data were analyzed in terms of functional connectivity (FC) between various resting-state networks as well as amplitude of low-frequency fluctuation (ALFF) and fractional amplitude of low-frequency fluctuations (fALFF). Results: Two-sample t-test revealed between-group differences in FC of posterior salience network (SN). No differences occurred in default mode network (DMN) and sensorimotor network (SMN). Moreover, differences in fALFF were shown in the right middle frontal gyrus and right superior frontal gyrus, however, no ALFF differences took place. Conclusion: Current study revealed significant functional network (FN) architecture between-group differences associated with fatigue. Present results suggest the higher level of fatigue is related to deficits in awareness as well as higher interoceptive awareness and nociception.

11.
Vaccines (Basel) ; 10(5)2022 May 12.
Artigo em Inglês | MEDLINE | ID: mdl-35632519

RESUMO

(1) Background: The present study aims to report the side effects of vaccination against coronavirus disease 2019 (COVID-19) among patients with multiple sclerosis (MS) who were being treated with disease-modifying therapies (DMTs) in Poland. (2) Methods: The study included 2261 patients with MS who were being treated with DMTs, and who were vaccinated against COVID-19 in 16 Polish MS centers. The data collected were demographic information, specific MS characteristics, current DMTs, type of vaccine, side effects after vaccination, time of side-effect symptom onset and resolution, applied treatment, relapse occurrence, and incidence of COVID-19 after vaccination. The results were presented using maximum likelihood estimates of the odds ratio, t-test, Pearson's chi-squared test, Fisher's exact p, and logistic regression. The statistical analyses were performed using STATA 15 software. (3) Of the 2261 sampled patients, 1862 (82.4%) were vaccinated with nucleoside-modified messenger RNA (mRNA) vaccines. Mild symptoms after immunization, often after the first dose, were reported in 70.6% of individuals. Symptoms included arm pain (47.5% after the first dose and 38.7% after the second dose), fever/chills/flu-like symptoms (17.1% after the first dose and 20.5% after the second dose), and fatigue (10.3% after the first dose and 11.3% after the second dose). Only one individual presented with severe side effects (pro-thrombotic complications) after vaccination. None of the DMTs in the presented cohort were predisposed to the development of side effects. Nine patients (0.4%) had a SARS-CoV-2 infection confirmed despite vaccination. (4) Conclusions: Vaccination against SARS-CoV-2 is safe for people with MS who are being treated with DMTs. Most adverse events following vaccination are mild and the acute relapse incidence is low.

12.
J Cancer Res Clin Oncol ; 148(6): 1325-1336, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-35089395

RESUMO

PURPOSE: The risk assessment classification schemes for gastrointestinal stromal tumors (GIST) include tumor site, size, mitotic count and variably tumor rupture. Heterogeneity in high-risk GIST poses limitations for current classification schemes. This study aims to demonstrate the clinical utility of risk stratification by gene expression profiling (GEP) using Nanostring technology. METHODS: Fifty-six GIST cases were analyzed using a 231 gene expression panel. GEP results were correlated with clinical and pathological data. The prognostic performance was assessed in 34 patients with available survival data using ROC curves, Kaplan-Meier survival curves and compared with traditional risk assessment schemes. Volcano plot analysis identified seven genes with significantly higher expression (FDR < .0.05) in high-risk than in non-high-risk tumors, namely TYMS, CDC2, TOP2A, CCNA2, E2F1, PCNA, and BIRC5. Together, these transcripts exhibited significantly higher expression in high-risk tumors than in intermediate (P < 0.01), low (P < 0.001), and very low (P = 0.01) risk tumors. Receiver-operating characteristic curve analysis demonstrated area under the curve (AUC) to be 0.858 for the separation of high-risk and non-high-risk tumors. Kaplan-Meier survival analysis demonstrated improved risk stratification (log-rank test P < 0.001) compared to the current risk assessment classification (P = 0.231). CONCLUSION: In addition to current clinical and histology-based risk classification for patients with GIST, gene expression may offer complementary prognostic information.


Assuntos
Tumores do Estroma Gastrointestinal , Tumores do Estroma Gastrointestinal/genética , Tumores do Estroma Gastrointestinal/patologia , Perfilação da Expressão Gênica , Humanos , Recidiva Local de Neoplasia/patologia , Prognóstico , Estudos Retrospectivos , Medição de Risco/métodos
13.
J Clin Med ; 10(22)2021 Nov 10.
Artigo em Inglês | MEDLINE | ID: mdl-34830507

RESUMO

(1) Background: To report and analyze the presence of residual symptoms after SARS-CoV-2 infection among Polish patients with multiple sclerosis (MS) treated with different disease-modifying therapies (DMTs). (2) Methods: The study included 426 individuals with MS treated with DMTs and confirmed SARS-CoV-2 infection from 12 Polish MS centers. The data were collected through to 31 May 2021. The information included demographics, specific MS characteristics, course of SARS-CoV-2 infection, and residual (general and neurological) symptoms lasting more than four and 12 weeks after the initial infection. The results were obtained using maximum likelihood estimates for odds ratio and logistic regression. (3) Results: A total of 44.84% patients with MS reported symptoms lasting between four and 12 weeks after the initial infection; 24.41% people had symptoms that resolved up to 12 weeks, and 20.42% patients had symptoms that lasted over 12 weeks. The most common symptoms were: fatigue, disturbance of concentration, attention, and memory, cognitive complaints, and headache. None of the DMTs were predisposed to the development of residual symptoms after the initial infection. A total of 11.97% of patients had relapse three months prior or after SARS-CoV-2 infection. (4) Conclusion: Almost half of individuals with MS treated with different DMTs had residual symptoms after SARS-CoV-2 infection. None of the DMTs raised the probability of developing post-acute COVID symptoms.

14.
Neurol Neurochir Pol ; 55(3): 314-321, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34037979

RESUMO

OBJECTIVES: To evaluate the spectrum of neurological symptoms in patients with COVID-19 during the first 14 days of hospitalisation and its association with in-hospital mortality. MATERIAL AND METHODS: We included 200 patients with RT-PCR-confirmed COVID-19 admitted to University Hospital in Krakow, Poland. In 164 patients, a detailed questionnaire concerning neurological symptoms and signs was performed prospectively within 14 days of hospitalisation. In the remaining 36 patients, such questionnaires were completed retrospectively based on daily observations in the Department of Neurology. RESULTS: During hospitalisation, 169 patients (84.5%) experienced neurological symptoms; the most common were: fatigue (62.5%), decreased mood (45.5%), myalgia (43.5%), and muscle weakness (42.5%). Patients who died during hospitalisation compared to the remainder were older (79 [70.5-88.5] vs. 63.5 [51-77] years, p = 0.001), and more often had decreased level of consciousness (50.0% vs. 9.3%, p < 0.001), delirium (33.3% vs. 4.4%, p < 0.001), arterial hypotension (50.0% vs. 19.6%, p = 0.005) or stroke during (18.8% vs. 3.3%, p = 0.026) or before hospitalisation (50.0% vs. 7.1, p < 0.001), whereas those who survived more often suffered from headache (42.1% vs. 0%, p = 0.012) or decreased mood (51.7% vs. 0%, p = 0.003). CONCLUSIONS: Most hospitalised patients with COVID-19 experience neurological symptoms. Decreased level of consciousness, delirium, arterial hypotension, and stroke during or before hospitalisation increase the risk of in-hospital mortality.


Assuntos
COVID-19 , Mortalidade Hospitalar , Humanos , Polônia , Estudos Retrospectivos , SARS-CoV-2
15.
J Stroke Cerebrovasc Dis ; 30(2): 105525, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33338755

RESUMO

OBJECTIVES: The impact of contracting stroke-associate infection (SAI) that requires antibiotic treatment after an acute ischemic stroke (AIS) treated with alteplase remains unclear. We studied the profiles of SAI in patients with AIS treated with alteplase toward identifying predictive factors and prognostic implications at 90 days post-stroke. METHODS: We analyzed 33 parameters readily available within 24 hours after AIS: demographics, risk factors, and several clinical and biochemical parameters. Outcome measures were mRS ≤ 2 and mortality 90 days post-stroke. RESULTS: 83 (23.6%) of 352 patients developed SAI. Multivariate logistic regression analysis showed that atrial fibrillation, mRS above 0 pre-stroke, lower delta NIHSS (the difference between NIHSS score measured upon admission and 24 hours after later), CRP≥10 mg/L, and elevated WBC count affected SAI risk (model including CRP levels and WBC count) and atrial fibrillation, mRS above 0 pre-stroke, lower delta NIHSS, HT, and elevated fibrinogen levels affected SAI risk (model excluding CRP levels and WBC count). 231 patients (74.1%) had mRS ≤ 2 at day 90. Multivariate logistic regression analysis showed that younger age, no hypertension, mRS=0 pre-stroke, higher delta NIHSS, no HT, no SAI, and CRP<10 mg/L, were associated with mRS≤2 at day 90. 54 (15.3%) patients died within 90 days. Multivariate logistic regression analysis showed that pre-stroke mRS>0, lower delta NIHSS, HT, CRP≥10 mg/L, lower triglyceride levels affected the risk of death within 90 days. CONCLUSIONS: Several markers available within 24 hours post-stroke were predictive of SAI that requires antibiotic treatment. SAI affects long-term outcome but not mortality.


Assuntos
Doenças Transmissíveis/microbiologia , Fibrinolíticos/administração & dosagem , AVC Isquêmico/tratamento farmacológico , Terapia Trombolítica , Ativador de Plasminogênio Tecidual/administração & dosagem , Idoso , Idoso de 80 Anos ou mais , Antibacterianos/uso terapêutico , Doenças Transmissíveis/diagnóstico , Doenças Transmissíveis/tratamento farmacológico , Doenças Transmissíveis/mortalidade , Bases de Dados Factuais , Feminino , Fibrinolíticos/efeitos adversos , Humanos , Infusões Intravenosas , AVC Isquêmico/complicações , AVC Isquêmico/diagnóstico , AVC Isquêmico/mortalidade , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Medição de Risco , Fatores de Risco , Terapia Trombolítica/efeitos adversos , Terapia Trombolítica/mortalidade , Fatores de Tempo , Ativador de Plasminogênio Tecidual/efeitos adversos , Resultado do Tratamento
16.
Gut ; 70(10): 1894-1903, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-32933947

RESUMO

OBJECTIVE: To describe the clinical, pathological and genomic characteristics of pancreatic cancer with DNA mismatch repair deficiency (MMRD) and proficiency (MMRP). DESIGN: We identified patients with MMRD and MMRP pancreatic cancer in a clinical cohort (N=1213, 519 with genetic testing, 53 with immunohistochemistry (IHC)) and a genomic cohort (N=288 with whole-genome sequencing (WGS)). RESULTS: 12 out of 1213 (1.0%) in the clinical cohort were MMRD by IHC or WGS. Of the 14 patients with Lynch syndrome, 3 (21.4%) had an MMRP pancreatic cancer by IHC, and 4 (28.6%) were excluded because tissue was unavailable for testing. MMRD cancers had longer overall survival after surgery (weighted HR after coarsened exact matching 0.11, 95% CI 0.02 to 0.78, p=0.001). One patient with an unresectable MMRD cancer has an ongoing partial response 3 years after starting treatment with PD-L1/CTLA-4 inhibition. This tumour showed none of the classical histopathological features of MMRD. 9 out of 288 (3.1%) tumours with WGS were MMRD. Despite markedly higher tumour mutational burden and neoantigen loads, MMRD cancers were significantly less likely to have mutations in usual pancreatic cancer driver genes like KRAS and SMAD4, but more likely to have mutations in genes that drive cancers with microsatellite instability like ACV2RA and JAK1. MMRD tumours were significantly more likely to have a basal-like transcriptional programme and elevated transcriptional markers of immunogenicity. CONCLUSIONS: MMRD pancreatic cancers have distinct clinical, pathological and genomic profiles. Patients with MMRD pancreatic cancer should be considered for basket trials targeting enhanced immunogenicity or the unique genomic drivers in these malignancies.


Assuntos
Adenocarcinoma/genética , Distúrbios no Reparo do DNA/genética , Neoplasias Pancreáticas/genética , Adenocarcinoma/patologia , Neoplasias Colorretais Hereditárias sem Polipose/genética , Neoplasias Colorretais Hereditárias sem Polipose/patologia , Distúrbios no Reparo do DNA/patologia , Feminino , Testes Genéticos , Genômica , Humanos , Masculino , Instabilidade de Microssatélites , Mutação , Ontário , Neoplasias Pancreáticas/patologia , Estudos Retrospectivos , Sequenciamento Completo do Genoma
17.
Semin Diagn Pathol ; 38(3): 195-198, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33288347

RESUMO

The SWItch Sucrose non-fermentable (SWI/SNF) complex is a large, multi-subunit ATP-dependent nucleosome remodeling complex that acts as a tumor suppressor by modulating transcription. Mutations of SWI/SNF subunits have been described in relation to developmental disorders, hereditary SWI/SNF deficiency syndromes, as well as malignancies. In this review we summarize the current literature in regards to SWI/SNF-deficient tumors of the luminal gastrointestinal tract (GIT) and pancreas. As a group they range from moderately to undifferentiated tumors composed of monotonous anaplastic cells, prominent macronucleoli and a variable rhabdoid cell component. Deficiency of a SWI/SNF subunit is typified by complete loss of nuclear staining by immunohistochemistry for respective subunit.


Assuntos
Neoplasias , Fatores de Transcrição , Humanos , Imuno-Histoquímica , Proteínas Nucleares , Sacarose , Fatores de Transcrição/genética
18.
Arch Pathol Lab Med ; 145(3): 365-370, 2021 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-32649836

RESUMO

CONTEXT.­: Laparoscopic sleeve gastrectomy (LSG) has quickly become the bariatric surgical procedure of choice for patients with obesity who have failed medical management. Laparoscopic sleeve gastrectomy results in a gastric remnant that is routinely subject to pathologic examination. OBJECTIVE.­: To perform a histologic and cost-benefit analysis of gastric remnants post-LSG. DESIGN.­: All LSG cases performed at University Health Network, Toronto, Ontario, Canada, between 2010 and 2019 were reviewed. Specimens that underwent routine histopathologic assessment and ancillary immunohistochemical analysis were analyzed. Baseline patient characteristics and surgical outcomes were obtained from our internal database. The total cost of specimen gross preparation, examination, sampling, and producing and reporting a hematoxylin-eosin slide was calculated. RESULTS.­: A total of 572 patients underwent LSG during the study period and had their specimens examined histologically. A mean of 4.87 blocks generating 4 hematoxylin-eosin slides was produced. The most common histologic findings reported in LSG specimens ranged from no pathologic abnormalities identified together with proton pump inhibitor-related change. A minority of cases demonstrated clinically actionable histologic findings, of which Helicobacter pylori infection was the most common. The total cost for the complete pathologic analysis of these cases amounted to CaD $66 383.10 (US $47 080.21) with a mean of CaD $116.05 (US $82.40) per case. A total of CaD $62 622.75 (US $44 413.30) was spent on full examination of cases that had no further postoperative clinical impact. CONCLUSIONS.­: There is a broad spectrum of pathologic findings in LSG specimens, ranging from clinically nonactionable to more clinically actionable. The vast majority of histologic findings had no clinical impact, with only a minority of cases being clinically significant. This study therefore recommends that LSG specimens be subject to gross pathologic examination in the vast majority of cases. However, sections should be submitted for microscopic analysis if grossly evident lesions are present and if there is a clinical/known history of clinically actionable findings.


Assuntos
Gastrectomia/economia , Infecções por Helicobacter/patologia , Helicobacter pylori/isolamento & purificação , Laparoscopia/economia , Obesidade Mórbida/patologia , Adulto , Cirurgia Bariátrica , Análise Custo-Benefício , Feminino , Infecções por Helicobacter/diagnóstico , Infecções por Helicobacter/cirurgia , Humanos , Masculino , Pessoa de Meia-Idade , Obesidade Mórbida/diagnóstico , Obesidade Mórbida/cirurgia , Ontário
19.
Neurol Neurochir Pol ; 54(6): 538-543, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33202029

RESUMO

AIM OF STUDY: Mechanical thrombectomy (MT) is one of the aetiological treatment options recommended for anticoagulated patients with acute ischaemic stroke (AIS). We analysed its long-term outcomes using the modified Rankin Score (mRS) or mortality on day 90. CLINICAL RATIONALE FOR THE STUDY: Data describing the anticoagulant efficacy and safety of MT in patients with AIS is limited. MATERIALS AND METHODS: This study included 291 patients with AIS (49% women, mean [SD] age 66 [15] years) who underwent MT in the Comprehensive Stroke Centre in Krakow, Poland. Data describing demographics, stroke risk factors, NIHSS on admission, postprocedural thrombolysis in cerebral infarction score, 24-hour postprocedural haemorrhagic transformation (ECASS-2) as seen on computed tomography, and time between stroke onset and groin puncture was collected. The outcome measure was the mRS on day 90 after stroke onset (a favourable outcome was defined as an mRS not exceeding 2 points; an unfavourable outcome was death). RESULTS: Thirty-seven patients (13%) were on therapeutic anticoagulation during MT. Univariate analysis showed that anticoagulated patients were older and more likely to have been diagnosed with hypertension, ischaemic heart disease, or atrial fibrillation. The patient groups did not differ in terms of clot location, postprocedural thrombolysis in cerebral infarction score, haemorrhagic transformation on computed tomography, or mRS on day 90. Multivariate logistic regression analysis showed that younger age, male sex, no history of diabetes mellitus, lower NIHSS score on admission, shorter time between stroke onset and groin puncture, and better recanalisation were associated with favourable outcomes at day 90, and that therapeutic anticoagulation was not (OR, 1.00; 95%CI, 0.46-2.15; p = 0.99). Anticoagulation did not affect mortality at day 90 (OR, 1.28; 95%CI, 0.56-2.92; p = 0.55). CONCLUSION AND CLINICAL IMPLICATIONS: In anticoagulated patients with AIS, MT does not affect long-term outcomes.


Assuntos
Isquemia Encefálica , AVC Isquêmico , Acidente Vascular Cerebral , Anticoagulantes/uso terapêutico , Isquemia Encefálica/tratamento farmacológico , Feminino , Humanos , Masculino , Polônia , Estudos Retrospectivos , Acidente Vascular Cerebral/tratamento farmacológico , Trombectomia , Resultado do Tratamento
20.
J Clin Pathol ; 73(10): 618-623, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32591353

RESUMO

BACKGROUND: Bariatric surgical procedures are employed when there is a failure of lifestyle modification in arresting obesity. Laparoscopic sleeve gastrectomy (LSG) is quickly becoming the bariatric surgical procedure of choice. LSG results in a gastric remnant that is subject to pathological examination. The objective of this paper is to review the literature in regard to histological findings identified in gastric remnants post-LSG and identify the most pertinent histological findings. MATERIALS AND METHODS: A literature search was performed to identify relevant case series. Data gathered from relevant case series then underwent statistical analysis. RESULTS: The most common histological findings in an LSG specimen were clinically indolent findings such as no pathological abnormalities identified followed by non-specific gastritis. A minority of cases demonstrated clinically actionable findings for which Helicobacter pylori represented the majority of these findings. CONCLUSION: There is a broad spectrum of pathological findings in LSG specimens, ranging from clinically indolent to clinically actionable. The most common histological findings are clinically indolent and only a small portion are of clinical significance and, hence, actionable.


Assuntos
Obesidade Mórbida/patologia , Obesidade Mórbida/cirurgia , Estômago/patologia , Adulto , Cirurgia Bariátrica , Feminino , Gastrectomia , Humanos , Laparoscopia , Masculino , Pessoa de Meia-Idade
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