RESUMEN
Pancreatic ductal adenocarcinoma (PDAC) is the fourth leading cause of cancer-related death in the Western world. The number of diagnosed cases and the mortality rate are almost equal as the majority of patients present with advanced disease at diagnosis. Between 4 and 10% of pancreatic cancer cases have an apparent hereditary background, known as hereditary pancreatic cancer (HPC) and familial pancreatic cancer (FPC), when the genetic basis is unknown. Surveillance of high-risk individuals (HRI) from these families by imaging aims to detect PDAC at an early stage to improve prognosis. However, the genetic basis is unknown in the majority of HRIs, with only around 10-13% of families carrying known pathogenic germline mutations. The aim of this study was to assess an individual's genetic cancer risk based on sex and personal and family history of cancer. The Best Linear Unbiased Prediction (BLUP) methodology was used to estimate an individual's predicted risk of developing cancer during their lifetime. The model uses different demographic factors in order to estimate heritability. A reliable estimation of heritability for pancreatic cancer of 0.27 on the liability scale, and 0.07 at the observed data scale as obtained, which is different from zero, indicating a polygenic inheritance pattern of PDAC. BLUP was able to correctly discriminate PDAC cases from healthy individuals and those with other cancer types. Thus, providing an additional tool to assess PDAC risk HRI with an assumed genetic predisposition in the absence of known pathogenic germline mutations.
Asunto(s)
Carcinoma Ductal Pancreático , Predisposición Genética a la Enfermedad , Mutación de Línea Germinal , Neoplasias Pancreáticas , Humanos , Carcinoma Ductal Pancreático/genética , Neoplasias Pancreáticas/genética , Femenino , Masculino , Persona de Mediana Edad , Adulto , Anciano , Medición de Riesgo/métodos , CarcinomaRESUMEN
The Spanish Familial Pancreatic Cancer Registry (PANGENFAM) was established in 2009 and aims to characterize the genotype and phenotype of familial pancreatic cancer (FPC). Furthermore, an early detection screening program for pancreatic ductal adenocarcinoma (PDAC) is provided to healthy high-risk individuals from FPC and hereditary pancreatic cancer families (first-degree relatives). This article describes our experience over the last 10 years in high-risk screening. Hereditary and familial pancreatic cancer families were identified through the oncology and gastroenterology units. High-risk individuals underwent annual screening with endoscopic ultrasound (EUS) and magnetic resonance (MRI) from age 40 or 10 years younger than the youngest affected family member. Results: PANGENFAM has enrolled 290 individuals from 143 families, including 52 PDAC cases and 238 high-risk individuals. All high-risk individuals eligible for screening were offered to enter the surveillance program, with 143 currently participating. Pancreatic abnormalities were detected in 94 individuals (median age 53 years (29-83), with common findings including cystic lesions and inhomogeneous parenchyma. Imaging test concordance was 66%. Surgical intervention was performed in 4 high-risk individuals following highly suspicious lesions detected by imaging. PANGENFAM is a valuable resource for science innovation, such as biobanking, with clinical and imaging data available for analysis. For high-risk families, it may offer a potential for early diagnosis. Collaboration with other national and international registries is needed to increase our understanding of the disease biology and to standardize criteria for inclusion and follow-up, optimizing cost-effectiveness and efficacy.
Asunto(s)
Carcinoma Ductal Pancreático , Neoplasias Pancreáticas , Sistema de Registros , Humanos , Neoplasias Pancreáticas/genética , Persona de Mediana Edad , España , Femenino , Masculino , Adulto , Anciano , Estudios de Seguimiento , Carcinoma Ductal Pancreático/genética , Carcinoma Ductal Pancreático/diagnóstico por imagen , Carcinoma Ductal Pancreático/diagnóstico , Anciano de 80 o más Años , Predisposición Genética a la Enfermedad , Detección Precoz del Cáncer/métodos , Imagen por Resonancia Magnética , Endosonografía , Factores de Riesgo , CarcinomaRESUMEN
BACKGROUND: Autoimmune pancreatitis [AIP] is rarely associated with inflammatory bowel disease [IBD]. The long-term outcomes of AIP and IBD in patients with coexisting AIP-IBD and predictors of complicated AIP course have rarely been reported. METHODS: An ECCO COllaborative Network For Exceptionally Rare case reports project [ECCO-CONFER] collected cases of AIP diagnosed in patients with IBD. Complicated AIP was defined as a composite of endocrine and/or exocrine pancreatic insufficiency, and/or pancreatic cancer. We explored factors associated with complicated AIP in IBD. RESULTS: We included 96 patients [53% males, 79% ulcerative colitis, 72% type 2 AIP, age at AIP diagnosis 35â ±â 16 years]. The majority of Crohn's disease [CD] cases [78%] had colonic/ileocolonic involvement. In 59%, IBD preceded AIP diagnosis, whereas 18% were diagnosed simultaneously. Advanced therapy to control IBD was used in 61% and 17% underwent IBD-related surgery. In total, 82% of patients were treated with steroids for AIP, the majority of whom [91%] responded to a single course of treatment. During a mean follow-up of 7 years, AIP complications occurred in 25/96 [26%] individuals. In a multivariate model, older age at AIP diagnosis was associated with a complicated AIP course (odds ratio [OR]â =â 1.05, pâ =â 0.008), whereas family history of IBD [ORâ =â 0.1, pâ =â 0.03], and CD diagnosis [ORâ =â 0.2, pâ =â 0.04] decreased the risk of AIP complications. No IBD- or AIP-related deaths occurred. CONCLUSIONS: In this large international cohort of patients with concomitant AIP-IBD, most patients have type 2 AIP and colonic IBD. AIP course is relatively benign and long-term outcomes are favourable, but one-quarter develop pancreatic complications. Age, familial history of IBD, and CD may predict uncomplicated AIP course.
Asunto(s)
Enfermedades Autoinmunes , Pancreatitis Autoinmune , Colitis Ulcerosa , Enfermedad de Crohn , Enfermedades Inflamatorias del Intestino , Pancreatitis , Masculino , Humanos , Adulto Joven , Adulto , Persona de Mediana Edad , Femenino , Pancreatitis Autoinmune/complicaciones , Pancreatitis/epidemiología , Pancreatitis/etiología , Estudios Retrospectivos , Enfermedades Autoinmunes/complicaciones , Enfermedades Autoinmunes/epidemiología , Enfermedades Inflamatorias del Intestino/complicaciones , Enfermedades Inflamatorias del Intestino/diagnóstico , Colitis Ulcerosa/complicaciones , Colitis Ulcerosa/diagnóstico , Colitis Ulcerosa/terapia , Enfermedad de Crohn/complicaciones , Enfermedad de Crohn/diagnóstico , Enfermedad de Crohn/epidemiologíaRESUMEN
BACKGROUND: Endoscopic resection (ER) is an emerging therapeutic alternative for subepithelial gastrointestinal lesions (SELs). We aimed to determine whether size, layer of origin, and histology based on endoscopic ultrasound (EUS) and EUS-guided sampling (EUS-GS) influenced the outcomes and selection of patients for ER. METHODS: We performed a retrospective review of patients who underwent EUS, EUS-GS and resection of SELs from 2012-2019. Two pathologists reviewed the histology and layer of origin of all resected specimens, serving as the criterion for EUS accuracy. RESULTS: Seventy-three patients were included, of whom 59 (81%) were gastric SELs. Per EUS, median lesion size was 21 mm (interquartile range 15-32), and 63 (86%) originated from the 4th layer. The overall accuracy of EUS and EUS-GS in predicting the layer of origin and histology was 88% (95% confidence interval [CI] 77-94%) and 96% (95%CI 87-98%), respectively. Based on EUS, 18 (25%) patients were referred for ER, 5 (7%) to laparoscopic-endoscopic cooperative surgery, and 50 (68%) to surgery. Size >20 mm was associated with the type of resection approach (P=0.005), while layer of origin and histology were not (P=0.06 and P=0.09, respectively). When SELs were inaccurately classified (n=4) there were no adverse events or revision of the resection approach. CONCLUSIONS: EUS plays an important role in the outcome of resection approach for SELs, with size significantly influencing the selection for ER. In patients undergoing ER, no revised resections were needed when EUS was inaccurate.