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1.
Scand J Gastroenterol ; 54(6): 733-739, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31401889

RESUMO

Background: Familial adenomatous polyposis (FAP) is characterized by the development of hundreds of colorectal adenomas in the second decade of life, and prophylactic colectomy is usually performed around age of 20. A common question is the appropriate timing of surgery and which endoscopic findings indicate surgery. Methods: All FAP patients known at Leiden University Medical Centre from 1985 onwards were included. The patients were then subdivided into those diagnosed before or after 2000. Patient information included age at diagnosis, colonic phenotype, age at surgery, pathological findings and the outcome of follow-up colonoscopies in whom surgery was postponed. Results: The 72 FAP patients identified consisted of 33 patients diagnosed before (group A) and 39 after (group B) 2000. The median age at diagnosis for patients with classical FAP was 18 in groups A and B. All patients diagnosed before 2000 underwent colorectal surgery versus 68% of those diagnosed >2000. The median age at surgery for classical FAP patients was 19 and 24 years in groups A and B, respectively. In patients with intact colon, the number of adenomas gradually increased over many years. Although most adenomas remained <5 mm, the proportion of 5-15 mm adenomas slowly increased. Only one patient developed a high-grade adenoma. None of the patients developed CRC. Conclusions: Surgery today in FAP is performed less often and at a more advanced age. Our experience also suggests that surgery can be safely postponed in selected patients. The most important endoscopic indication for surgery is substantial number of large adenomas of >5-10 mm.

2.
J Med Genet ; 56(9): 581-589, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31186341

RESUMO

BACKGROUND: The currently known breast cancer-associated single nucleotide polymorphisms (SNPs) are presently not used to guide clinical management. We explored whether a genetic test that incorporates a SNP-based polygenic risk score (PRS) is clinically meaningful in non-BRCA1/2 high-risk breast cancer families. METHODS: 101 non-BRCA1/2 high-risk breast cancer families were included; 323 cases and 262 unaffected female relatives were genotyped. The 161-SNP PRS was calculated and standardised to 327 population controls (sPRS). Association analysis was performed using a Cox-type random effect regression model adjusted by family history. Updated individualised breast cancer lifetime risk scores were derived by combining the Breast and Ovarian Analysis of Disease Incidence and Carrier Estimation Algorithm breast cancer lifetime risk with the effect of the sPRS. RESULTS: The mean sPRS for cases and their unaffected relatives was 0.70 (SD=0.9) and 0.53 (SD=0.9), respectively. A significant association was found between sPRS and breast cancer, HR=1.16, 95% CI 1.03 to 1.28, p=0.026. Addition of the sPRS to risk prediction based on family history alone changed screening recommendations in 11.5%, 14.7% and 19.8 % of the women according to breast screening guidelines from the USA (National Comprehensive Cancer Network), UK (National Institute for Health and Care Excellence and the Netherlands (Netherlands Comprehensive Cancer Organisation), respectively. CONCLUSION: Our results support the application of the PRS in risk prediction and clinical management of women from genetically unexplained breast cancer families.

3.
Fam Cancer ; 18(3): 349-352, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-31111311

RESUMO

Subtotal colectomy is usually the therapy of choice in Lynch syndrome patients diagnosed with colon cancer. In patients who develop cancer after the age of 50-60 years, segmental colectomy is considered a good alternative. Although the endoscopic treatment of early colorectal cancer in non-Lynch patients has increased in the last decades, almost all patients with a Lynch syndrome-associated colorectal malignancy undergo surgery, even if the tumour is diagnosed in a (very) early stage. One of the endoscopic treatment options for early colorectal cancer is an endoscopic full thickness resection (eFTR). This treatment modality allows optimal pathological examination of the resection specimen, as a transmural resection is performed with optimal T-staging of the tumour. We report a case of a 62 year old man, diagnosed with MSH2-Lynch syndrome, who underwent successful eFTR treatment of an early (pT1) colon cancer located in the ascending colon, with no signs of recurrence 12 months after treatment. We discuss the pros and cons of endoscopic resection of early colorectal carcinoma in Lynch syndrome patients.

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.
HPB (Oxford) ; 2019 Mar 22.
Artigo em Inglês | MEDLINE | ID: mdl-30910317

RESUMO

BACKGROUND: MRI surveillance in a cohort of CDKN2A-p16-Leiden mutation carriers with a 20% lifetime risk of PDAC led to increased resection rates and improved survival. Patients with screen-detected PDAC were evaluated for main pancreatic duct (MPD) abnormalities in this retrospective review. METHODS: Since 2000 annual MRI and optional EUS was performed in mutation carriers. Data of patients with screen-detected PDAC was collected on gender, age at diagnosis, site of tumor, size, outcome of surgery, pathology findings and survival. All MRIs were re-evaluated for MPD abnormalities. RESULTS: 23 PDAC were detected in 22 (10%) of 217 mutation carriers, 10 (45%) males and 12 (55%) females. The mean age at diagnosis was 59.8 years (range 39.2-74.3 years). Revision of the MRI/MRCP revealed a lesion and dilatation of the MPD in 8 of the 22 patients. In 5 of 7 patients with PDAC detected during follow-up, the previous MRI showed MPD dilatation without evidence of tumor. The mean size of PDAC was 12.3 mm (range 5-19 mm). All tumors were resectable. CONCLUSION: MPD dilation is common in patients with screen-detected PDAC. Abnormalities on MRI during surveillance of high-risk individuals requires intense follow-up or prompt treatment, as early treatment results in a better prognosis.

7.
J Clin Oncol ; 36(29): 2961-2968, 2018 Oct 10.
Artigo em Inglês | MEDLINE | ID: mdl-30161022

RESUMO

PURPOSE: Lynch syndrome due to pathogenic variants in the DNA mismatch repair genes MLH1, MSH2, and MSH6 is predominantly associated with colorectal and endometrial cancer, although extracolonic cancers have been described within the Lynch tumor spectrum. However, the age-specific cumulative risk (penetrance) of these cancers is still poorly defined for PMS2-associated Lynch syndrome. Using a large data set from a worldwide collaboration, our aim was to determine accurate penetrance measures of cancers for carriers of heterozygous pathogenic PMS2 variants. METHODS: A modified segregation analysis was conducted that incorporated both genotyped and nongenotyped relatives, with conditioning for ascertainment to estimates corrected for bias. Hazard ratios (HRs) and corresponding 95% CIs were estimated for each cancer site for mutation carriers compared with the general population, followed by estimation of penetrance. RESULTS: In total, 284 families consisting of 4,878 first- and second-degree family members were included in the analysis. PMS2 mutation carriers were at increased risk for colorectal cancer (cumulative risk to age 80 years of 13% [95% CI, 7.9% to 22%] for males and 12% [95% CI, 6.7% to 21%] for females) and endometrial cancer (13% [95% CI, 7.0%-24%]), compared with the general population (6.6%, 4.7%, and 2.4%, respectively). There was no clear evidence of an increased risk of ovarian, gastric, hepatobiliary, bladder, renal, brain, breast, prostate, or small bowel cancer. CONCLUSION: Heterozygous PMS2 mutation carriers were at small increased risk for colorectal and endometrial cancer but not for any other Lynch syndrome-associated cancer. This finding justifies that PMS2-specific screening protocols could be restricted to colonoscopies. The role of risk-reducing hysterectomy and bilateral salpingo-oophorectomy for PMS2 mutation carriers needs further discussion.

8.
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.

9.
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.

10.
J Med Genet ; 55(10): 661-668, 2018 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-29661971

RESUMO

BACKGROUND: Several factors have been reported that influence the probability of a germline CDKN2A mutation in a melanoma family. Our goal was to create a scoring system to estimate this probability, based on a set of clinical features present in the patient and his or her family. METHODS: Five clinical features and their association with CDKN2A mutations were investigated in a training cohort of 1227 Dutch melanoma families (13.7% with CDKN2A mutation) using multivariate logistic regression. Predefined features included number of family members with melanoma and with multiple primary melanomas, median age at diagnosis and presence of pancreatic cancer or upper airway cancer in a family member. Based on these five features, a scoring system (CDKN2A Mutation(CM)-Score) was developed and subsequently validated in a combined Swedish and Dutch familial melanoma cohort (n=421 families; 9.0% with CDKN2A mutation). RESULTS: All five features were significantly associated (p<0.05) with a CDKN2A mutation. At a CM-Score of 16 out of 49 possible points, the threshold of 10% mutation probability is approximated (9.9%; 95% CI 9.8 to 10.1). This probability further increased to >90% for families with ≥36 points. A CM-Score under 16 points was associated with a low mutation probability (≤4%). CM-Score performed well in both the training cohort (area under the curve (AUC) 0.89; 95% CI 0.86 to 0.92) and the external validation cohort (AUC 0.94; 95% CI 0.90 to 0.98). CONCLUSION: We developed a practical scoring system to predict CDKN2A mutation status among melanoma-prone families. We suggest that CDKN2A analysis should be recommended to families with a CM-Score of ≥16 points.

11.
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
13.
Gut ; 67(7): 1306-1316, 2018 07.
Artigo em Inglês | MEDLINE | ID: mdl-28754778

RESUMO

BACKGROUND: Most patients with path_MMR gene variants (Lynch syndrome (LS)) now survive both their first and subsequent cancers, resulting in a growing number of older patients with LS for whom limited information exists with respect to cancer risk and survival. OBJECTIVE AND DESIGN: This observational, international, multicentre study aimed to determine prospectively observed incidences of cancers and survival in path_MMR carriers up to 75 years of age. RESULTS: 3119 patients were followed for a total of 24 475 years. Cumulative incidences at 75 years (risks) for colorectal cancer were 46%, 43% and 15% in path_MLH1, path_MSH2 and path_MSH6 carriers; for endometrial cancer 43%, 57% and 46%; for ovarian cancer 10%, 17% and 13%; for upper gastrointestinal (gastric, duodenal, bile duct or pancreatic) cancers 21%, 10% and 7%; for urinary tract cancers 8%, 25% and 11%; for prostate cancer 17%, 32% and 18%; and for brain tumours 1%, 5% and 1%, respectively. Ovarian cancer occurred mainly premenopausally. By contrast, upper gastrointestinal, urinary tract and prostate cancers occurred predominantly at older ages. Overall 5-year survival for prostate cancer was 100%, urinary bladder 93%, ureter 85%, duodenum 67%, stomach 61%, bile duct 29%, brain 22% and pancreas 0%. Path_PMS2 carriers had lower risk for cancer. CONCLUSION: Carriers of different path_MMR variants exhibit distinct patterns of cancer risk and survival as they age. Risk estimates for counselling and planning of surveillance and treatment should be tailored to each patient's age, gender and path_MMR variant. We have updated our open-access website www.lscarisk.org to facilitate this.


Assuntos
Neoplasias do Colo/epidemiologia , Neoplasias Colorretais Hereditárias sem Polipose/complicações , Neoplasias Colorretais Hereditárias sem Polipose/mortalidade , Neoplasias Pancreáticas/epidemiologia , Neoplasias Urogenitais/epidemiologia , Fatores Etários , Idoso , Neoplasias Colorretais Hereditárias sem Polipose/patologia , Bases de Dados Factuais , Feminino , Humanos , Incidência , Masculino , Estudos Prospectivos
14.
Endosc Int Open ; 5(7): E622-E626, 2017 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-28691043

RESUMO

BACKGROUND AND STUDY AIMS : Lynch syndrome (LS) patients have an increased risk of small bowel cancer. The question is whether surveillance will lead to early detection of (pre)malignant lesions. We recently reported on prevalence of small bowel neoplasia (SBN) in LS patients as assessed by video capsule endoscopy (VCE). The aim of this prospective study was to determine the incidence of SBN. PATIENTS AND METHODS : Asymptomatic LS patients who underwent a VCE were invited to undergo a second VCE procedure 2 years later. If abnormalities or polypoid lesions larger than 1 cm were detected, subsequent endoscopic procedures were performed. RESULTS : A total of 155 (78 %) of the initial 200 patients underwent a second VCE procedure after a mean of 2.2 (range 1 - 6) years. In 17 of the 155 (11 %) patients possibly significant lesions were detected, which required further investigation by means of gastroduodenoscopy (n = 8) or balloon-assisted endoscopy (n = 9). These procedures revealed no SBN. CONCLUSION : No SBN was found after 2 years. Surveillance of the small bowel by VCE does not seem to be warranted in asymptomatic LS patients.

15.
Fam Cancer ; 16(1): 111-115, 2017 01.
Artigo em Inglês | MEDLINE | ID: mdl-27406244

RESUMO

In 3-5 % of all cases of pancreatic ductal adenocarcinoma (PDAC), hereditary factors influence etiology. While surveillance of high-risk individuals may improve the prognosis, this study describes two very different outcomes in patients with screen-detected lesions. In 2000, a surveillance program of carriers of a CDKN2A/p16-Leiden-mutation consisting of annual MRI was initiated. Patients with a suspected pancreatic lesion undergo CT-scan and Endoscopic Ultrasound, and surgery is offered when a lesion is confirmed. In 2015, two patients with a screen-detected solid lesion were identified. In both patients, lesions were visible on MRI and CT scan, while the EUS was unremarkable. Surgical resection of the head of the pancreas resulted in nearly fatal complications in the first patient. This patient was shown to have a benign lesion. In contrast, timely identification of an early cancer in the second patient was accompanied by an uneventful postoperative course. These cases underline the risks inherent to a PDAC prevention program. All patients should be fully informed about the possible outcomes before joining a surveillance program.


Assuntos
Carcinoma Ductal Pancreático/diagnóstico por imagem , Neoplasias Pancreáticas/diagnóstico por imagem , Carcinoma Ductal Pancreático/genética , Carcinoma Ductal Pancreático/patologia , Inibidor de Quinase Dependente de Ciclina p18/genética , Heterozigoto , Humanos , Imagem por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Neoplasias Pancreáticas/genética , Neoplasias Pancreáticas/patologia , Tomografia Computadorizada por Raios X
16.
J Clin Pathol ; 70(2): 174-178, 2017 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-27672215

RESUMO

To improve the diagnostic value of fine-needle aspiration (FNA)-derived material, we perform targeted next-generation sequencing (NGS) in patients with a suspect lesion of the pancreas. The NGS analysis can lead to a change in the treatment plan or supports inconclusive or uncertain cytology results. We describe the advantages of NGS using one particular patient with a recurrent pancreatic lesion 7 years after resection of a pancreatic ductal adenocarcinoma (PDAC). Our NGS analysis revealed the presence of a presumed second primary cancer in the pancreatic remnant, which led to a change in treatment: resection with curative intend instead of palliation. Additionally, NGS identified an unexpected germline CDKN2A 19-base pair deletion, which predisposed the patient to developing PDAC. Preoperative NGS analysis of FNA-derived DNA can help identify patients at risk for developing PDAC and define future therapeutic options.


Assuntos
Carcinoma Ductal Pancreático/patologia , Neoplasias Pancreáticas/patologia , Biópsia por Agulha Fina , Carcinoma Ductal Pancreático/metabolismo , Carcinoma Ductal Pancreático/cirurgia , DNA , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias Pancreáticas/metabolismo , Neoplasias Pancreáticas/cirurgia , Análise de Sequência de DNA , Resultado do Tratamento
18.
Br J Cancer ; 115(10): 1174-1178, 2016 Nov 08.
Artigo em Inglês | MEDLINE | ID: mdl-27755534

RESUMO

BACKGROUND: It is unknown whether a history of breast cancer (BC) affects the outcome of BRCA1/2-associated epithelial ovarian cancer (EOC). This was investigated in the current analysis. METHODS: We included 386 BRCA1/2-associated EOC patients diagnosed between 1980 and 2015. Progression-free survival (PFS), progression-free interval (PFI), overall survival (OS) and ovarian cancer-specific survival (OCSS) were compared between EOC patients with and without previous BC. RESULTS: BRCA-associated EOC patients with, vs without, a BC history had a significantly worse PFS and PFI (multivariate hazard ratio (HRmult) 1.47; 95% confidence interval (CI) 1.03-2.08 and HRmult 1.43; 95% CI 1.01-2.03), and a non-significantly worse OS (HRmult 1.15; 95% CI 0.84-1.57) and OCSS (HRmult 1.18; 95% CI 0.85-1.62). Ovarian cancer-specific survival was significantly worse for the subgroup treated with adjuvant chemotherapy for BC (HRmult 1.99; 95% CI 1.21-3.31). CONCLUSIONS: Our results suggest that BRCA1/2-associated EOC patients with a previous BC have a worse outcome than EOC patients without BC, especially when treated with adjuvant chemotherapy.


Assuntos
Proteína BRCA1/genética , Proteína BRCA2/genética , Neoplasias da Mama/genética , Neoplasias da Mama/mortalidade , Mutação/genética , Neoplasias Ovarianas/genética , Neoplasias Ovarianas/mortalidade , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma Epitelial do Ovário , Intervalo Livre de Doença , Feminino , Humanos , Pessoa de Meia-Idade , Neoplasias Epiteliais e Glandulares/genética , Prognóstico , Adulto Jovem
19.
Scand J Gastroenterol ; 51(10): 1227-32, 2016 10.
Artigo em Inglês | MEDLINE | ID: mdl-27310819

RESUMO

OBJECTIVES: In 2014, a population-screening program using immuno-faecal occult blood testing (I-FOBT) has started in the Netherlands. The aims of this study were to evaluate the proportion of individuals in the Dutch screening program with a positive I-FOBT that fulfill the criteria for familial colorectal cancer (FCC) and to evaluate the proportion of participants that needs genetic counseling or colonoscopic surveillance. MATERIAL AND METHODS: This retrospective observational study was performed in two large hospitals. Individuals aged between 55 and 75 years with a positive I-FOBT that underwent colonoscopy were included. A detailed family history was obtained in all individuals. RESULTS: A total of 657 individuals with a positive I-FOBT test underwent colonoscopy. A total of 120 (18.3%) participants were found to have a positive family history for CRC, 20 (3.0%) fulfilled the FCC criteria, 4 (0.6%) the Bethesda guidelines and 1 (0.2%) participant the Amsterdam criteria. Multiple adenomas (>10) were found in 21 (3.2%) participants. No cases of serrated polyposis were identified. Based on these criteria and guidelines, a total of 35 (5.3%) required referral to the clinical geneticist and the relatives of 20 (3.0%) participants should be referred for surveillance colonoscopy. CONCLUSION: Obtaining a detailed family history at the time of intake of participants with a positive I-FOBT in the Dutch surveillance program increased the identification of participants with familial CRC.


Assuntos
Adenoma/epidemiologia , Neoplasias Colorretais Hereditárias sem Polipose/diagnóstico , Neoplasias Colorretais Hereditárias sem Polipose/epidemiologia , Idoso , Colonoscopia , Aconselhamento , Feminino , Humanos , Masculino , Programas de Rastreamento , Pessoa de Meia-Idade , Países Baixos , Sangue Oculto , Projetos Piloto , Vigilância da População , Encaminhamento e Consulta , Estudos Retrospectivos
20.
Transl Oncol ; 9(3): 242-7, 2016 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-27267843

RESUMO

BACKGROUND: Pancreatic cancer (PC) surveillance is currently offered to individuals with a genetic predisposition to PC, but routinely used radiological screening modalities are not entirely reliable in detecting early-stage PC or its precursor lesions. We recently identified a discriminating PC biomarker signature in a sporadic patient cohort. In this study, we investigated if protein profiling can accurately distinguish PC from non-PC in a pancreatic surveillance cohort of genetically predisposed individuals. METHODS: Serum samples of 66 individuals with a CDKN2A germline mutation who participated in the pancreatic surveillance program (5 cases, 61 controls) were obtained following a standardized protocol. After sample clean-up, peptide and protein profiles were obtained on an ultrahigh-resolution matrix-assisted laser desorption/ionization-Fourier transform ion cyclotron resonance mass spectrometry platform. A discriminant score for each sample was calculated with a previously designed prediction rule, and the median discriminant scores of cases and controls were compared. Individuals with precursor lesions of PC (n = 4) and individuals with a recent diagnosis of melanoma (n = 4) were also separately considered. RESULTS: Cases had a higher median discriminant score than controls (0.26 vs 0.016; P = .001). The only individual with pathologically confirmed precursor lesions of PC could also be clearly distinguished from controls, and having a (recent) medical history of melanoma did not influence the protein signatures. CONCLUSIONS: Peptide and protein signatures are able to accurately distinguish PC cases from controls in a pancreatic surveillance setting. Mass spectrometry-based protein profiling therefore seems to be a promising candidate for implementation in the pancreatic surveillance program as an additional screening modality.

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