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1.
Eur J Hum Genet ; 2019 Sep 16.
Artigo em Inglês | MEDLINE | ID: mdl-31527860

RESUMO

This study aimed to determine the prevalence of APC-associated familial adenomatous polyposis (FAP) and MUTYH-associated polyposis (MAP) in a large cohort, taking into account factors as adenoma count and year of diagnosis. All application forms used to send patients in for APC and MUTYH variant analysis between 1992 and 2017 were collected (n = 2082). Using the data provided on the application form, the APC and biallelic MUTYH prevalence was determined and possible predictive factors were examined using multivariate multinomial logistic regression analysis in SPSS. The prevalence of disease causing variants in the APC gene significantly increases with adenoma count while MAP shows a peak prevalence in individuals with 50-99 adenomas. Logistic regression analysis shows significant odds ratios for adenoma count, age at diagnosis, and, interestingly, a decline in the chance of finding a variant in either gene over time. Moreover, in 22% (43/200) of patients with FAP-related extracolonic manifestations a variant was identified. The overall detection rates are above 10% for patients with >10 adenomas aged <60 and >20 adenomas aged <70. Patients with variants outside these criteria had FAP-related extracolonic manifestations, colorectal cancer aged <40, somatic KRAS c.34G > T variant in the tumor or a first-degree relative with >10 adenomas. Therefore, APC and MUTYH testing in patients with >10 adenomas aged <60 and with >20 adenomas aged <70 is advised. Almost all FAP and MAP patients not meeting these criteria showed other characteristics that can be used as an indication to prompt genetic testing.

2.
Eur J Endocrinol ; 181(3): P1-P19, 2019 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-31176307

RESUMO

PARAT, a new European Society of Endocrinology program, aims to identify unmet scientific and educational needs of parathyroid disorders, such as primary hyperparathyroidism (PHPT), including parathyroid cancer (PC), and hypoparathyroidism (HypoPT). The discussions and consensus statements from the first PARAT workshop (September 2018) are reviewed. PHPT has a high prevalence in Western communities, PHPT has a high prevalence in Western communities, yet evidence is sparse concerning the natural history and whether morbidity and long-term outcomes are related to hypercalcemia or plasma PTH concentrations, or both. Cardiovascular mortality and prevalence of low energy fractures are increased, whereas Quality of Life is decreased, although their reversibility by treatment of PHPT has not been convincingly demonstrated. PC is a rare cause of PHPT, with an increasing incidence, and international collaborative studies are required to advance knowledge of the genetic mechanisms, biomarkers for disease activity, and optimal treatments. For example, ~20% of PCs demonstrate high mutational burden, and identifying targetable DNA variations, gene amplifications and gene fusions may facilitate personalized care, such as different forms of immunotherapy or targeted therapy. HypoPT, a designated orphan disease, is associated with a high risk of symptoms and complications. Most cases are secondary to neck surgery. However, there is a need to better understand the relation between disease biomarkers and intellectual function, and to establish the role of PTH in target tissues, as these may facilitate the appropriate use of PTH substitution therapy. Management of parathyroid disorders is challenging, and PARAT has highlighted the need for international transdisciplinary scientific and educational studies in advancing in this field.


Assuntos
Educação/métodos , Endocrinologia/educação , Endocrinologia/métodos , Doenças das Paratireoides/tratamento farmacológico , Sociedades Médicas , Europa (Continente)/epidemiologia , Humanos , Hiperparatireoidismo Primário/diagnóstico , Hiperparatireoidismo Primário/tratamento farmacológico , Hiperparatireoidismo Primário/metabolismo , Doenças das Paratireoides/diagnóstico , Doenças das Paratireoides/metabolismo , Hormônio Paratireóideo/uso terapêutico , Neoplasias das Paratireoides/diagnóstico , Neoplasias das Paratireoides/tratamento farmacológico , Neoplasias das Paratireoides/metabolismo
4.
Fam Cancer ; 18(3): 343-348, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-31114938

RESUMO

A high colorectal cancer (CRC) incidence is observed in Tunisia, with a relatively high proportion of patients developing CRC before the age of 40. While this suggests a genetic susceptibility, only a few Tunisian Lynch Syndrome families have been described. In this study we aimed to identify the underlying genetic cause in 32 patients with early onset CRC and/or a positive family history. Of twenty-four patients' tumor or biopsies could be analyzed with immunohistochemical staining to detect loss of expression of one of the MMR proteins. Ten tumors showed loss of expression, of which one tumor was from a patient where a germline pathogenic MSH2 variant was detected previously with Sanger sequencing. Next generation sequencing of the MMR, POLE and POLD1 genes was performed in leukocyte and tumor DNA of the remaining nine patients, as well as in two patients with MMR-proficient tumors, but with severe family history. In six of 11 patients a germline variant was detected in MLH1 (n = 5) or MSH2 (n = 1). Two of six patients were from the same family and both were found to carry a novel in-frame MLH1 deletion, predicted to affect MLH1 function. All MLH1 variant carriers had loss of heterozygosity with retention of the variant in the tumors, while a somatic pathogenic variant was detected in the patient with the germline MSH2 variant.

5.
Mol Genet Genomic Med ; 7(4): e00603, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30827058

RESUMO

BACKGROUND: Germline mutations affecting the exonuclease domains of POLE and POLD1 predispose to colorectal adenomas and carcinoma. Here, we aimed to screen the exonuclease domains to find the genetic causes of multiple colorectal polyps in unexplained cases. METHODS: Using a custom next-generation sequencing panel, we sequenced the exonuclease domains of POLE and POLD1 in 332 index patients diagnosed with multiple colorectal polyps without germline alteration in colorectal polyposis predisposing genes. RESULTS: We identified two variants of unknown significance. One germline POLD1 c.961G>A, p.(Gly321Ser) variant was found in two cases. The first patient was diagnosed with multiple polyps at age 35 and colorectal cancer (CRC) at age 37, with no known family history of CRC. The second patient was diagnosed with CRC at age 44 and cumulatively developed multiple polyps; this patient had two sisters with endometrial cancer who did not carry the variant. Furthermore, we identified a novel POLD1 c.955 T>G, p.(Cys319Gly) variant in a patient diagnosed with multiple colorectal adenomas at age 40. Co-segregation analysis showed that one sister who cumulatively developed multiple adenomas from age 34, and another sister who developed CRC at age 38 did not carry the variant. We did not identify pathogenic variants in POLE and POLD1. CONCLUSION: This study confirms the low frequency of causal variants in these genes in the predisposition for multiple colorectal polyps, and also establishes that these genes are a rare cause of the disease.


Assuntos
Pólipos do Colo/genética , Neoplasias Colorretais/genética , DNA Polimerase III/genética , DNA Polimerase II/genética , Taxa de Mutação , Proteínas de Ligação a Poli-ADP-Ribose/genética , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Domínio Catalítico , DNA Polimerase II/química , DNA Polimerase III/química , Feminino , Mutação em Linhagem Germinativa , Humanos , Masculino , Pessoa de Meia-Idade , Mutação de Sentido Incorreto , Proteínas de Ligação a Poli-ADP-Ribose/química
6.
Br J Cancer ; 120(8): 815-818, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30862951

RESUMO

In colorectal cancer (CRC), T-cell checkpoint blockade is only effective in patients diagnosed with mismatch repair-deficient (MMR-d) cancers. However, defects in Human Leukocyte Antigen (HLA) class I expression were reported to occur in most MMR-d CRCs, which would preclude antigen presentation in these tumours, considered essential for the clinical activity of this immunotherapeutic modality. We revisited this paradox by characterising HLA class I expression in two independent cohorts of CRC. We determined that loss of HLA class I expression occurred in the majority (73-78%) of MMR-d cases. This phenotype was rare in CRC liver metastases, irrespective of MMR status, whereas weak, inducible expression of HLA class I molecules was frequent in liver lesions. We propose that HLA class I is an important determinant of metastatic homing in CRCs. This observation is paramount to understand CRC carcinogenesis and for the application of immunotherapies in the metastatic setting.

7.
Cancer Cell ; 35(2): 256-266.e5, 2019 Feb 11.
Artigo em Inglês | MEDLINE | ID: mdl-30753826

RESUMO

Biallelic germline mutations affecting NTHL1 predispose carriers to adenomatous polyposis and colorectal cancer, but the complete phenotype is unknown. We describe 29 individuals carrying biallelic germline NTHL1 mutations from 17 families, of which 26 developed one (n = 10) or multiple (n = 16) malignancies in 14 different tissues. An unexpected high breast cancer incidence was observed in female carriers (60%). Mutational signature analysis of 14 tumors from 7 organs revealed that NTHL1 deficiency underlies the main mutational process in all but one of the tumors (93%). These results reveal NTHL1 as a multi-tumor predisposition gene with a high lifetime risk for extracolonic cancers and a typical mutational signature observed across tumor types, which can assist in the recognition of this syndrome.

8.
Endocr Relat Cancer ; 2018 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-30576283

RESUMO

In their back-to-back published articles "Integrated Genomic Analysis of Hürthle Cell Cancer Reveals Oncogenic Drivers, Recurrent Mitochondrial Mutations, and Unique Chromosomal Landscapes" and "Widespread Chromosomal Losses and Mitochondrial DNA Alterations as Genetic Drivers in Hürthle Cell Carcinoma" Ganly and co-workers (Ganly, et al. 2018) and Gopal and co-workers (Gopal, et al. 2018), respectively, defined alterations in oncogenic drivers and mitochondrial DNA mutations complex I (mtDNA), including the widespread whole-chromosome losses in oncocytic or Hürthle cell thyroid carcinoma (HCC). This comprehensive analysis further unravels the unique features of HCC, either minimal or widely invasive in character and confirms previous work published on mtDNA mutations as well as the widespread loss of entire chromosomes (Bonora, et al. 2006; Corver, et al. 2012; Corver, et al. 2014; Gasparre, et al. 2007).

9.
Artigo em Inglês | MEDLINE | ID: mdl-30260442

RESUMO

Context: The DICER1 syndrome is a rare, autosomal dominant inherited disorder that predisposes to a variety of cancerous and noncancerous tumors of mostly pediatric- and adolescent-onset, including differentiated thyroid carcinoma (DTC). DICER1-related DTC has been hypothesized to arise secondary to the increased prevalence of pre-malignant lesions, i.e. thyroid hyperplastic nodules. Objective: To determine somatic alterations in DICER1-associated differentiated thyroid cancer and to study patient outcomes. Design: Retrospective series. Setting: Tertiary referral centers. Patients: Ten patients with germline pathogenic DICER1 variants and early-onset DTC. Investigation: Somatic DICER1 mutation analysis and extensive somatic DNA variant and gene fusion analyses on all tumors. Results: Median age at DTC diagnosis was 13.5 years and no patients developed recurrent or metastatic disease (median follow-up 8 years). All thyroid specimens showed diffuse nodular hyperplasia with at least one focus suspect for DTC, but without infiltrative growth, extra-thyroidal extension, vascular invasion, or lymph node metastasis. Distinct somatic DICER1 RNase IIIb domain variants were identified in most presumed-malignant (and benign) nodules tested from each patient's tumor, suggestive of multiple distinct poly-clonal tumors. Furthermore, 9 of 10 DICER1-related DTC lacked well known oncogenic driver DNA variants and gene rearrangements. Conclusions: On the basis of our clinical, histological and molecular data, we consider that the majority of DICER1-related DTCs form a low-risk subgroup. As these tumors may arise from one of many benign polyclonal nodules, hemi- or more likely total thyroidectomy may be often required, but radioiodine treatment may be unnecessary, given the patients age and their low propensity for metastases.

10.
Oncotarget ; 9(59): 31502-31515, 2018 Jul 31.
Artigo em Inglês | MEDLINE | ID: mdl-30140386

RESUMO

The tumor microenvironment is a dominant determinant of cancer cell behavior. Reactive tumor stroma is associated with poor outcome perspective. The tumor-stroma ratio (TSR) is a strong independent prognostic factor in colorectal cancer and is easily assessed using conventional hematoxylin and eosin (H&E) stained paraffin sections at the invasive margin of the tumor. We aim to understand the biology of the tumor stroma in colorectal cancer by investigating the transcriptomic profiles of tumors classified by the TSR method. The TSR was assessed in a cohort of 71 colorectal cancer patients undergoing surgery without (neo)adjuvant therapy. In the cohort, stroma-high tumors were distinguished from stroma-low tumors at gene expression level in the upregulation of biological pathways related to extracellular matrix (ECM) remodeling and myogenesis. The activated microenvironment in stroma-high tumors overexpressed different types of collagen genes, THBS2 and 4 as well as INHBA, COX71A and LGALS1/galectin-1. The upregulation of THBS2, COX7A1 and LGALS1/galectin-1. The upregulation of THBS2, COX7A1 and LGALS1/galectin-1 in stroma-high tumors was validated in The Cancer Genome Atlas. In conclusion, the gene expression data reflects the high stromal content of tumors assessed based on the histological method, the TSR. The composition of the microenvironment suggests an altered proteolysis resulting in ECM remodeling and invasive capacity of tumor cells.

12.
Cancer Prev Res (Phila) ; 11(9): 551-556, 2018 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-29991580

RESUMO

CDKN2A-p16-Leiden mutation carriers have a 20% to 25% risk of developing pancreatic ductal adenocarcinoma (PDAC). Better understanding of the natural course of PDAC might allow the surveillance protocol to be improved. The aims of the study were to evaluate the role of cystic precursor lesions in the development of PDAC and to assess the growth rate. In 2000, a surveillance program was initiated, consisting of annual MRI in carriers of a CDKN2A-p16-Leiden mutation. The study cohort included 204 (42% male) patients. Cystic precursor lesions were found in 52 (25%) of 204 mutation carriers. Five (9.7%) of 52 mutation carriers with cystic lesions and 8 (7.0%) of 114 mutation carriers without cystic lesions developed PDAC (P = 0.56). Three of 6 patients with a cystic lesion of ≥10 mm developed PDAC. The median size of all incident PDAC detected between 9 and 12 months since the previous normal MRI was 15 mm, suggesting an annual growth rate of about 15 mm/year. In conclusion, our findings show that patients with and without a cystic lesions have a similar risk of PDAC. However, cystic precursor lesions between 10 and 20 mm increase the risk of PDAC substantially. In view of the large size of the screen-detected tumors, a shorter interval of screening might be recommended for all patients. Cancer Prev Res; 11(9); 551-6. ©2018 AACR.

13.
Gastroenterology ; 155(3): 844-851, 2018 09.
Artigo em Inglês | MEDLINE | ID: mdl-29758216

RESUMO

BACKGROUND & AIMS: Germline variants in mismatch repair genes MLH1, MSH2 (EPCAM), MSH6, or PMS2 cause Lynch syndrome. Patients with these variants have an increased risk of developing colorectal cancers (CRCs) that differ from sporadic CRCs in genetic and histologic features. It has been a challenge to study CRCs associated with PMS2 variants (PMS2-associated CRCs) because these develop less frequently and in older patients than CRCs with variants in other mismatch repair genes. METHODS: We analyzed 20 CRCs associated with germline variants in PMS2, 22 sporadic CRCs, 18 CRCs with germline variants in MSH2, and 24 CRCs from patients with germline variants in MLH1. Tumor tissue blocks were collected from Dutch pathology departments in 2017. After extraction of tumor DNA, we used a platform designed to detect approximately 3,000 somatic hotspot variants in 55 genes (including KRAS, APC, CTNNB1, and TP53). Somatic variant frequencies were compared using the Fisher exact test. RESULTS: None of the PMS2-associated CRCs contained any somatic variants in the catenin-ß1 gene (CTNNB1), which encodes ß-catenin, whereas 14 of 24 MLH1-associated CRCs (58%) contained variants in CTNNB1. Half the PMS2-associated CRCs contained KRAS variants, but only 20% of these were in hotspots that encoded G12D or G13D. These hotspot variants occurred more frequently in CRCs associated with variants in MLH1 (37.5%; P = .44) and MSH2 (71.4%; P = .035) than in those associated with variants in PMS2. CONCLUSIONS: In a genetic analysis of 84 colorectal tumors, we found tumors from patients with PMS2-associated Lynch syndrome to be distinct from colorectal tumors associated with defects in other mismatch repair genes. This might account for differences in development and less frequent occurrence.


Assuntos
Neoplasias Colorretais Hereditárias sem Polipose/genética , Neoplasias Colorretais/genética , Mutação em Linhagem Germinativa , Endonuclease PMS2 de Reparo de Erro de Pareamento/genética , Adulto , Idoso , Reparo de Erro de Pareamento de DNA , Proteínas de Ligação a DNA/genética , Molécula de Adesão da Célula Epitelial/genética , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Proteína 1 Homóloga a MutL/genética , beta Catenina/genética
14.
Eur J Hum Genet ; 26(8): 1227-1229, 2018 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-29769629

RESUMO

CDKN2A-p16-Leiden mutation carriers have a substantial risk of developing pancreatic ductal adenocarcinoma (PDAC). One of the main clinical features of hereditary cancer is the development of multiple cancers. Since 2000, we have run a surveillance program for CDKN2A-p16-Leiden mutation carriers. The patients are offered a yearly MRI with optionally endoscopic ultrasound. In patients with a confirmed lesion, usually, a partial resection of the pancreas is recommended. A total of 18 PDAC (8.3%) were detected in 218 mutation carriers. In this report, we describe two CDKN2A-p16-Leiden patients with a synchronous and metachronous PDAC. Including two previously-reported cases, we identified four patients with multiple PDAC: two of 18 patients within the surveillance program (11%) and two patients with a proven CDKN2A-p16-Leiden mutation not participating in the surveillance program. In conclusion, this study demonstrated a high risk of developing multiple PDAC in CDKN2A-p16-Leiden mutation carriers. After detecting a primary tumor, it is very important to exclude the presence of a second synchronous tumor. Moreover, after a partial pancreatectomy for PDAC, close surveillance is necessary. In view of the current findings, offering a total pancreatectomy might be an appropriate option in patients with an early PDAC.

15.
Eur J Hum Genet ; 26(8): 1143-1150, 2018 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-29706640

RESUMO

High-throughput sequencing efforts in molecular tumour diagnostics detect increasing numbers of novel variants, including variants predicted to affect splicing. In silico prediction tools can reliably predict the effect of variant disrupting canonical splice sites; however, experimental validation is required to confirm aberrant splicing. Here, we present RNA analysis performed for 13 canonical splice site variants predicted or known to result in splicing in the cancer predisposition genes MLH1, MSH2, MSH6, APC and BRCA1. Total nucleic acid was successfully isolated for 10 variants from eight formalin-fixed paraffin-embedded (FFPE) tumour tissues and two B-cell lines. Aberrant splicing was confirmed in all six variants known to result in splicing. Of one known variant in the B-cell line, aberrant splicing could only be detected after formalin fixation, which indicated that formalin fixation could possibly inhibit RNA degradation. Aberrant splicing was concluded in three of four predicted splice variants of uncertain significance, supporting their pathogenic effect. With this assay, somatic splice variants can be easily and rapidly analysed, enabling retrospective analysis to support the pathogenicity of variants predicted to result in splicing when only FFPE material is available.

16.
Virchows Arch ; 472(4): 533-543, 2018 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-29589102

RESUMO

A pancreatoduodenectomy specimen is complex, and there is much debate on how it is best approached by the pathologist. In this review, we provide an overview of topics relevant for current clinical practice in terms of gross dissection, and macro- and microscopic assessment of the pancreatoduodenectomy specimen with a suspicion of suspected pancreatic cancer. Tumor origin, tumor size, degree of differentiation, lymph node status, and resection margin status are universally accepted as prognostic for survival. However, different guidelines diverge on important issues, such as the diagnostic criteria for evaluating the completeness of resection. The macroscopic assessment of the site of origin in periampullary tumors and cystic lesions is influenced by the grossing method. Bi-sectioning of the head of the pancreas may offer an advantage in this respect, as this method allows for optimal visualization of the periampullary area. However, a head-to-head comparison of the assessment of clinically relevant parameters, using axial slicing versus bi-sectioning, is not available yet and the gold standard to compare both techniques prospectively might be subject of debate. Further studies are required to validate the various dissection protocols used for pancreatoduodenectomy specimens and their specific value in the assessment of pathological parameters relevant for prognosis.


Assuntos
Neoplasias dos Ductos Biliares/diagnóstico , Neoplasias Duodenais/diagnóstico , Neoplasias Pancreáticas/diagnóstico , Patologia Cirúrgica/métodos , Neoplasias dos Ductos Biliares/patologia , Neoplasias Duodenais/patologia , Humanos , Neoplasias Pancreáticas/patologia , Pancreaticoduodenectomia
17.
Histopathology ; 73(2): 197-206, 2018 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-29457843

RESUMO

The tumour microenvironment consists of a complex mixture of non-neoplastic cells, including fibroblasts, immune cells and endothelial cells embedded in the proteins of the extracellular matrix. The tumour microenvironment plays an active role in tumour behaviour. By interacting with cancer cells, it influences disease progression and the metastatic capacity of the tumour. Tumours with a high amount of stroma correspond to poor patient prognosis. The tumour-stroma ratio (TSR) is a strong independent prognostic tool in colon cancer and provides additional value to the current clinically used tumour-node-metastasis classification. The TSR is assessed on conventional haematoxylin and eosin-stained paraffin sections at the invasive front of the tumour. Here we review studies demonstrating the prognostic significance of the TSR in solid epithelial tumours with a focus on colon cancer. Moreover, the biological role of the tumour microenvironment during tumour progression and invasion will be discussed, as well as the attempts to target the tumour stroma for therapeutic purposes. We suggest that the TSR can be implemented with little effort and without additional costs in current routine pathology diagnostics owing to its simplicity and reliability.


Assuntos
Neoplasias do Colo/patologia , Microambiente Tumoral , Humanos , Prognóstico
19.
Endocr Rev ; 39(2): 154-191, 2018 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-29300866

RESUMO

Indeterminate thyroid cytology (Bethesda III and IV) corresponds to follicular-patterned benign and malignant lesions, which are particularly difficult to differentiate on cytology alone. As ~25% of these nodules harbor malignancy, diagnostic hemithyroidectomy is still custom. However, advanced preoperative diagnostics are rapidly evolving.This review provides an overview of additional molecular and imaging diagnostics for indeterminate thyroid nodules in a preoperative clinical setting, including considerations regarding cost-effectiveness, availability, and feasibility of combining techniques. Addressed diagnostics include gene mutation analysis, microRNA, immunocytochemistry, ultrasonography, elastosonography, computed tomography, sestamibi scintigraphy, [18F]-2-fluoro-2-deoxy-d-glucose positron emission tomography (FDG-PET), and diffusion-weighted magnetic resonance imaging.The best rule-out tests for malignancy were the Afirma® gene expression classifier and FDG-PET. The most accurate rule-in test was sole BRAF mutation analysis. No diagnostic had both near-perfect sensitivity and specificity, and estimated cost-effectiveness. Molecular techniques are rapidly advancing. However, given the currently available techniques, a multimodality stepwise approach likely offers the most accurate diagnosis, sequentially applying one sensitive rule-out test and one specific rule-in test. Geographical variations in cytology (e.g., Hürthle cell neoplasms) and tumor genetics strongly influence local test performance and clinical utility. Multidisciplinary collaboration and implementation studies can aid the local decision for one or more eligible diagnostics.

20.
J Clin Pathol ; 71(3): 246-252, 2018 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-28775172

RESUMO

AIMS: Radiological imaging and morphological assessment of cytology material have limitations for preoperative classification of pancreatic or periampullary lesions, often resulting in surgical resection without definitive diagnosis. Our prospective study aims to define the diagnostic value of targeted next-generation sequencing (NGS) of DNA from cytology material. METHODS: Patients with a suspect pancreatic or periampullary lesion underwent standard diagnostic evaluation including preoperative morphological cytology assessment. Treatment options for suspect lesions were surgical exploration with possible resection, follow-up or palliation. The cytology samples were analysed with NGS, in which 50 genes were sequenced for the presence of pathogenic variants. The NGS results were integrated with the clinical information during multidisciplinary team meetings, and changes in the treatment plan were scored. Diagnostic accuracy of NGS analysis (malignancy vs benign disease) was calculated. RESULTS: NGS results of the cytology samples were confirmed in the resection specimens of the first 10 included patients. The integration of the NGS results led to a change in treatment plan in 7 out of 70 patients (from exploration to follow-up, n=4; from follow-up to exploration and resection, n=2; from palliation to resection, n=1). In four patients, the NGS results were contradictory, but did not affect the treatment plan. In the remaining 59 patients, NGS analysis supported the initial treatment plan. The diagnostic accuracy of NGS analysis was 94% (sensitivity=93%; specificity=100%). CONCLUSIONS: NGS can change the treatment plan in a significant portion of patients with suspect pancreatic or periampullary lesions. Application of NGS can optimise treatment selection and diminish unnecessary surgeries.


Assuntos
Neoplasias do Ducto Colédoco/diagnóstico , Sequenciamento de Nucleotídeos em Larga Escala/métodos , Neoplasias Pancreáticas/diagnóstico , Idoso , Idoso de 80 Anos ou mais , Ampola Hepatopancreática/patologia , Estudos de Coortes , Neoplasias do Ducto Colédoco/genética , Neoplasias do Ducto Colédoco/patologia , Neoplasias do Ducto Colédoco/terapia , Citodiagnóstico , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Pâncreas/patologia , Neoplasias Pancreáticas/genética , Neoplasias Pancreáticas/patologia , Neoplasias Pancreáticas/terapia , Estudos Prospectivos , Análise de Sequência de DNA
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