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AIMS: Inflammatory myofibroblastic tumour (IMT) is a rare mesenchymal neoplasm of intermediate malignant potential, occurring at any age and at multiple sites. Epithelioid inflammatory myofibroblastic sarcoma (EIMS) is an aggressive subtype of IMT, typically involving the abdomen. Most IMTs harbour kinase gene fusions, especially involving ALK and ROS1, but 20-30% of IMTs show no detectable translocations. The aim of this study is to further delineate clinicopathological and molecular characteristics of abdominal IMT and discover potential new therapeutic targets. METHODS AND RESULTS: In 20 IMTs, including four EIMS, RNA fusion analysis was performed, followed by multiplex DNA analysis if no ALK or ROS1 fusion was detected. Fourteen IMTs (70.0%) had an ALK translocation and the fusion partner was identified in 11, including a RRBP1::ALK fusion, not previously described in classical (non-EIMS) IMT. RANBP2::ALK fusion was demonstrated in all EIMS. One IMT had a ROS1 fusion. In all ALK/ROS1 translocation-negative IMTs mutations or fusions - as yet unreported in primary IMT - were found in genes related to the receptor tyrosine kinase (RTK)/PI3K/AKT pathway. Three of four patients with EIMS died of disease [mean survival 8 months (4-15 months)], whereas only one of 14 classical IMT patients succumbed to disease [mean follow-up time 52 months (2-204 months); P < 0.01]. CONCLUSION: This study shows the wide clinical spectrum of abdominal IMTs and affirms the poor prognosis of EIMS, raising discussion about its status as IMT subtype. Furthermore, the newly detected alterations of the RTK/PI3K/AKT pathway expand the molecular landscape of IMTs and provide potential therapeutic targets.
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Proteínas Tirosina Quinasas , Sarcoma , Humanos , Quinasa de Linfoma Anaplásico/genética , Proteínas Tirosina Quinasas/genética , Fosfatidilinositol 3-Quinasas , Proteínas Proto-Oncogénicas c-akt , Proteínas Proto-Oncogénicas/genética , Proteínas Tirosina Quinasas Receptoras/genética , Sarcoma/genéticaRESUMEN
Bronchial stenosis is an uncommon but potentially life-threatening complication of granulomatosis with polyangiitis (GPA). The development of lower respiratory tract stenoses in patients with GPA is thought to be the result of persistent inflammation of the cartilaginous tissue. New assessment methods for this severe GPA complication are highly needed. Herein, we show the value of 18F-fluorodeoxyglycose positron emission tomography/computed tomography (18F-FDG-PET/CT) in the diagnosis, prediction of progression to bronchial stenosis and response to treatment of endobronchial involvement in a patient with GPA.
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Fluorodesoxiglucosa F18 , Granulomatosis con Poliangitis , Humanos , Tomografía Computarizada por Tomografía de Emisión de Positrones , Granulomatosis con Poliangitis/complicaciones , Granulomatosis con Poliangitis/diagnóstico por imagen , Constricción Patológica/complicaciones , Tomografía de Emisión de PositronesRESUMEN
Background and study aims Neuroendocrine neoplasms (NEN) account for a small number of colorectal neoplasms. Endoscopic detection is essential for diagnosis, treatment and follow-up. Little is known about incidence of NENs in colonoscopy populations or the relationship between clinical, endoscopic and histopathologic features. We evaluated epidemiology, endoscopic and clinical characteristics of colorectal NENs in a population-based cohort. Patients and methods Medical records of NEN cases were cross-linked with the national pathology database from January 2001 to December 2015, in South Limburg County, the Netherlands, covering four endoscopy units. Senior pathologists reviewed and classified NENs using World Health Organization 5th edition (2019) guidelines. Results The number of colorectal NEN diagnoses was stable over time with 0.6 NEN per 1,000 patients. A total of NENs were detected in 85 patients: 65 neuroendocrine tumors (NETs) and 20 poorly differentiated neuroendocrine carcinomas (NECs). Rectal NETs were usually small sessile/submucosal lesions with yellowish (lipoma-like) color. Colonic NETs were larger sessile/submucosal lesions with darker color compared to background. Colorectal NECs presented as large, dark-colored lesions with ulcerated/necrotizing areas. Conclusions Our population-based data point to a stable and low incidence of 0.6 NEN per 1,000 patients in the Netherlands. Rectal NETs mainly present as small sessile yellowish lesions. Colonic NETs present as larger and darker lesions than background mucosa and NECs as darker lesions than background with ulceration/necrosis. Standardized endoscopic characterization of colorectal NENs is necessary to improve recognition of these lesions and provide a basis for evidence-based treatment and surveillance recommendations.
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Recommendations in Barrett's esophagus (BE) guidelines are mainly based on male patients. We aimed to evaluate sex differences in BE patients in (1) probability of and (2) time to neoplastic progression, and (3) differences in the stage distribution of neoplasia. We conducted a multicenter prospective cohort study including 868 BE patients. Cox regression modeling and accelerated failure time modeling were used to estimate the sex differences. Neoplastic progression was defined as high-grade dysplasia (HGD) and/or esophageal adenocarcinoma (EAC). Among the 639 (74%) males and 229 females that were included (median follow-up 7.1 years), 61 (7.0%) developed HGD/EAC. Neoplastic progression risk was estimated to be twice as high among males (HR 2.26, 95% CI 1.11-4.62) than females. The risk of HGD was found to be higher in males (HR 3.76, 95% CI 1.33-10.6). Time to HGD/EAC (AR 0.52, 95% CI 0.29-0.95) and HGD (AR 0.40, 95% CI 0.19-0.86) was shorter in males. Females had proportionally more EAC than HGD and tended to have higher stages of neoplasia at diagnosis. In conclusion, both the risk of and time to neoplastic progression were higher in males. However, females were proportionally more often diagnosed with (advanced) EAC. We should strive for improved neoplastic risk stratification per individual BE patient, incorporating sex disparities into new prediction models.
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BACKGROUND: Microscopic colitis (MC) is a common cause of chronic watery diarrhea. Biopsies with characteristic histological features are crucial for establishing the diagnosis. The two main subtypes are collagenous colitis (CC) and lymphocytic colitis (LC) but incomplete forms exist. The disease course remains unpredictable varying from spontaneous remission to a relapsing course. AIM: To identify possible histological predictors of course of disease. METHODS: Sixty patients from the European prospective MC registry (PRO-MC Collaboration) were included. Digitised histological slides stained with CD3 and Van Gieson were available for all patients. Total cell density and proportion of CD3 positive lymphocytes in lamina propria and surface epithelium were estimated by automated image analysis, and measurement of the subepithelial collagenous band was performed. Histopathological features were correlated to the number of daily stools and daily watery stools at time of endoscopy and at baseline as well as the clinical disease course (quiescent, achieved remission after treatment, relapsing or chronic active) at 1-year follow-up. RESULTS: Neither total cell density in lamina propria, proportion of CD3 positive lymphocytes in lamina propria or surface epithelium, or thickness of collagenous band showed significant correlation to the number of daily stools or daily watery stools at any point of time. None of the assessed histological parameters at initial diagnosis were able to predict clinical disease course at 1-year follow-up. CONCLUSIONS: Our data indicate that the evaluated histological parameters were neither markers of disease activity at the time of diagnosis nor predictors of disease course.
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Colitis Colagenosa , Colitis Linfocítica , Colitis Microscópica , Colitis , Colitis Colagenosa/diagnóstico , Colitis Linfocítica/diagnóstico , Colitis Microscópica/diagnóstico , Humanos , Pronóstico , Estudios ProspectivosRESUMEN
BACKGROUND AND AIMS: Crohn's disease [CD] is characterised by a heterogeneous disease course. Patient stratification at diagnosis using clinical, serological, or genetic markers does not predict disease course sufficiently to facilitate clinical decision making. The current study aimed to investigate the additive predictive value of histopathological features to discriminate between a long-term mild and severe disease course. METHODS: Diagnostic biopsies from treatment-naïve CD patients with mild or severe disease courses in the first 10 years after diagnosis were reviewed by two gastrointestinal pathologists after developing a standardised form comprising 15 histopathological features. Multivariable logistic regression models were built to identify predictive features and compute receiver operating characteristic [ROC] curves. Models were internally validated using bootstrapping to obtain optimism-corrected performance estimates. RESULTS: In total, 817 biopsies from 137 patients [64 mild, 73 severe cases] were included. Using clinical baseline characteristics, disease course could only moderately be predicted (area under receiver operating characteristic curve [AUROC]: 0.738 [optimism 0.018], 95% confidence interval [CI] 0.65-0.83, sensitivity 83.6%, specificity 53.1%). When adding histopathological features, in colonic biopsies a combination of [1] basal plasmacytosis, [2] severe lymphocyte infiltration in lamina propria, [3] Paneth cell metaplasia, and [4] absence of ulcers were identified and resulted in significantly better prediction of a severe course (AUROC: 0.883 [optimism 0.033], 95% CI 0.82-0.94, sensitivity 80.4%, specificity 84.2%). CONCLUSIONS: In this first study investigating the additive predictive value of histopathological features in biopsies at CD diagnosis, we found that certain features of chronic inflammation in colonic biopsies contributed to prediction of a severe disease course, thereby presenting a novel approach to improving stratification and facilitating clinical decision making.
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Biopsia/métodos , Colon/patología , Enfermedad de Crohn/diagnóstico , Adulto , Estudios de Cohortes , Colon/fisiopatología , Enfermedad de Crohn/epidemiología , Enfermedad de Crohn/fisiopatología , Progresión de la Enfermedad , Humanos , Modelos Logísticos , Masculino , Persona de Mediana Edad , Curva ROC , Estudios Retrospectivos , Índice de Severidad de la EnfermedadRESUMEN
Microscopic colitis (MC) is the umbrella term for the conditions termed lymphocytic colitis (LC) and collagenous colitis (CC). LC with thickening of the subepithelial collagen band or CC with increased number of intraepithelial T- lymphocytes (IELs) is often seen in MC and may lead to difficulties in correct histological classification. We investigated the extent of overlapping features of CC and LC in 60 cases of MC by measuring the exact thickness of the subepithelial collagen band in Van Gieson stained slides and quantifying number of IELs in CD3 stained slides by digital image analysis. A thickened collagen band was observed in nine out of 29 cases with LC (31%) and an increased number of IELs in all 23 cases of CC (100%). There was no correlation between the thickness of the collagen band and number of IELs. Due to the increased number of IELs in all cases of CC we consider the lymphocytic inflammatory infiltration of the mucosa to be the essential histopathological feature of MC. However, although LC and CC are related due to the lymphocytic inflammation, the non-linear correlation of number of IELs and thickness of the collagenous band indicate differences in their pathogenesis.
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Colitis Colagenosa/patología , Colitis Linfocítica/patología , Colitis Microscópica/patología , Colágeno/metabolismo , Linfocitos Intraepiteliales/patología , Colitis Colagenosa/metabolismo , Colitis Linfocítica/metabolismo , Colitis Microscópica/metabolismo , Humanos , Procesamiento de Imagen Asistido por Computador/métodos , Linfocitos Intraepiteliales/metabolismo , Linfocitos Intraepiteliales/ultraestructura , Linfocitos/patología , Variaciones Dependientes del ObservadorRESUMEN
BACKGROUND: Laterally spreading tumours represent a major challenge for endoscopic detection and resection. OBJECTIVE: To examine synchronous and metachronous neoplasms in patients with laterally spreading tumours. METHODS: We prospectively collected colonoscopy and histopathology data from patients who underwent colonoscopy in our centre at up to 6 years' follow-up. Post-resection surveillance outcomes between laterally spreading tumours, flat colorectal neoplasms 10 mm or greater, and large polypoid colorectal neoplasms, polypoid colorectal neoplasms 10 mm or greater, were compared. RESULTS: Between 2008 and 2012, 8120 patients underwent colonoscopy for symptoms (84.6%), screening (6.7%) or surveillance (8.7%). At baseline, 151 patients had adenomatous laterally spreading tumours and 566 patients had adenomatous large polypoid colorectal neoplasms. Laterally spreading tumour patients had more synchronous colorectal neoplasms than large polypoid colorectal neoplasm patients (mean 3.34 vs. 2.34, p < 0.001). Laterally spreading tumour patients significantly more often developed metachronous colorectal neoplasms (71.6% vs. 54.2%, p = 0.0498) and colorectal neoplasms with high grade dysplasia/submucosal invasion than large polypoid colorectal neoplasm patients (36.4% vs. 15.8%, p < 0.001). After correction for age and gender, laterally spreading tumour patients were more likely than large polypoid colorectal neoplasm patients to develop a colorectal neoplasm with high grade dysplasia or submucosal invasion (hazard ratio 2.9, 95% confidence interval 1.8-4.6). The risk of metachronous colorectal cancer was not significantly different in laterally spreading tumours compared to large polypoid colorectal neoplasm patients. CONCLUSION: Patients with laterally spreading tumours developed more metachronous colorectal neoplasms with high grade dysplasia/submucosal invasion than large polypoid colorectal neoplasm patients. Based on these findings endoscopic treatment and surveillance recommendations for patients with laterally spreading tumours should be optimised.
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Neoplasias del Colon/patología , Neoplasias Primarias Múltiples/patología , Neoplasias Primarias Secundarias/patología , Adenoma/epidemiología , Adenoma/patología , Adenoma/cirugía , Anciano , Neoplasias del Colon/epidemiología , Neoplasias del Colon/cirugía , Colonoscopía/estadística & datos numéricos , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Clasificación del Tumor , Invasividad Neoplásica , Neoplasias Primarias Múltiples/epidemiología , Neoplasias Primarias Secundarias/epidemiología , Prevalencia , Estudios ProspectivosRESUMEN
The diagnosis of microscopic colitis (MC) relies on specific histopathological findings in colon biopsies. The number of biopsies needed to diagnose MC remains disputed. The aim of the study was to determine the number and site of biopsies necessary for the diagnosis and the effect of perpendicular orientation when embedding the biopsies. This retrospective multicenter European study included 42 patients with a consensus diagnosis of collagenous colitis (CC), 51 patients with lymphocytic colitis (LC), and three patients with incomplete LC (LCi). The number of individual diagnostic biopsies from each patient was determined. The diagnostic rate of 744 individual biopsies from 96 patients with MC was 69.5% for the specific MC subgroup, 79.4% for MC and 93.4% for MC plus incomplete MC (MCi). The risk of missing a diagnosis of the specific subgroup of MC when analyzing four biopsies was 0.87%, decreasing to 0.18% for MC and 0.0019% for MC plus MCi. More biopsies from the right colon were diagnostic of the specific MC subgroup (76.3% vs. 64.0%, p = 0.0014). Perpendicular orientation of biopsies increased the diagnostic rate of the specific MC subgroup (73.1% vs. 65.0%, p = 0.0201). Histological changes diagnostic of MC were present in almost all biopsies from the right colon, with orientated biopsies more often being diagnostic of the specific MC subgroup. The results of this study indicate that four biopsies from the colon, rectum excluded, are sufficient to diagnose MC.
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Biopsia/métodos , Colitis Microscópica/diagnóstico , Colitis Microscópica/patología , Adhesión en Parafina/métodos , Humanos , Estudios RetrospectivosRESUMEN
Microscopic colitis (MC) comprising lymphocytic colitis (LC), collagenous colitis (CC) and the incomplete forms of microscopic colitis (MCi) are frequent causes of chronic watery diarrhea. The diagnosis is based on specific histological features in colonic biopsies. Especially regarding MCi, the histological features may be subtle. The PRO-MC collaboration was established in 2016 with the aims to systematically describe the disease course and to validate the diagnostic criteria of MC. In the present study, we analysed pathologists' initial approach to diagnose MC. Five pathologists with expertise in gastro-intestinal pathology reviewed the first 10 cases enrolled in the PRO-MC registry in six of the participating centres. Despite considerable differences in strategies in biopsy sampling, in choice of stains and in minimum number of biopsies and segments required for diagnosing MC, inter-observer agreement between the participating centres and expert pathologists as well as among the latter was substantial. Disagreed cases most often related to difficulties in distinguishing between MC subgroups. We recommend that pathologists as well as clinicians reach consensus in their diagnostic approach to MC, which is a prerequisite to compare MC cohorts internationally and to facilitate clinical MC trials and follow-up studies.
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Colitis/diagnóstico , Patología Clínica/métodos , Patología Clínica/normas , Europa (Continente) , Humanos , Variaciones Dependientes del Observador , Patólogos , Pautas de la Práctica en Medicina/normasRESUMEN
OBJECTIVE: In selected rectal cancer patients with residual local disease following neoadjuvant chemoradiation (CRT) and the preference of an organ preservation pathway, additional treatment with dose escalation by endoluminal radiotherapy (RT) may ultimately result in a clinical complete response. To date, the widespread introduction of selective endoluminal radiation techniques is hampered by a lack of evidence-based guidelines that describe the radiation treatment volume in relation to the residual tumor mass. In order to convert an incomplete response into a complete one with additional treatment such as dose-escalation with endoluminal RT from a theoretical perspective, it seems important to treat all remaining microscopic tumor cells after CRT. In this setting, residual tumor extension beneath normal appearing mucosa (microscopic intramural spread - MIS) becomes relevant for accurate tumor volume and margin estimation. With the goal of providing evidence-based guidelines that define an appropriate treatment volume and patient selection, we present results from a meta-analysis based on individual patient data of studies that have assessed the extent or range of MIS of rectal cancers after neoadjuvant CRT. This meta-analysis should provide an estimate of the residual tumor volume/extension that needs to be targeted by any additional radiation therapy boost in order to achieve complete tumor eradication after initial incomplete or near-complete response following standard CRT. METHODS AND MATERIALS: A PubMed search was performed. Additional articles were selected based on identification from reference lists. Papers were eligible when reporting MIS in patients who were treated by total mesorectal excision or local excision/transanal endoscopic microsurgery (TEM) after neo-adjuvant long-course CRT. The mean MIS was calculated for the entire group along with the 70th until 95th percentiles. Additional exploratory subgroup analyses were performed. RESULTS: Individual patient data from 349 patients with residual disease from five studies were analyzed. 80% of tumors showed no MIS. In order to appropriately treat MIS in 95% of rectal cancer patients after CRT, a margin of 5.5â¯mm around the macroscopic tumor would suffice. An exploratory subgroup analysis showed that T-stage after CRT (ypT) and time interval between neoadjuvant CRT and surgery are significant factors predicting the extent of MIS (pâ¯<â¯0.001.) The group of ypT1 had the smallest MIS, followed by the ypT3-4 group, while the ypT2 group had the largest MIS (pâ¯<â¯0.001). Regarding time interval between CRT and surgery, a statistically significant difference was seen when comparing the three time-interval groups (less than 8â¯weeks, 8-12â¯weeks, and more than 12â¯weeks), where waiting more than 12â¯weeks after CRT resulted in the largest MIS (pâ¯<â¯0.0001). CONCLUSION: Based on this meta-analysis, in order to treat the MIS for 95% of rectal cancer patients after CRT, a Clinical Target Volume (CTV) margin of 5.5â¯mm from the lateral most edge of the macroscopic tumor would suffice. 80% of tumors showed no MIS and would not require an extra CTV margin for treatment. These findings support the feasibility of localized radiotherapy boosts for dose-escalation to improve response among patients with incomplete response after standard CRT and can also be applied in the surgical setting.
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Adenocarcinoma , Neoplasias del Recto , Adenocarcinoma/patología , Quimioradioterapia Adyuvante , Humanos , Terapia Neoadyuvante , Estadificación de Neoplasias , Neoplasias del Recto/patología , Neoplasias del Recto/terapia , Resultado del TratamientoRESUMEN
BACKGROUND: Microscopic colitis (MC) is considered a multifactorial disease, strongly associated with smoking. However, little is known about the role of environmental factors such as ambient air pollution in MC pathophysiology. There is an overlap in components of cigarette smoke and ambient air pollution. Therefore, the aim of this study was to explore an independent association between ambient air quality and MC. METHODS: A case-control study was performed. MC cases in South Limburg, the Netherlands, diagnosed between 2000 and 2012, were retrieved from the national pathology registry and matched to non-MC controls from the same area based on age (±2 years) and gender. A stable residential address for ≥3 years was required. Residential land use, proximity to major road, and concentrations of air pollution compounds, were determined using a Geographic Information System (GIS). Univariate and multivariable regression analyses were corrected for age, gender and smoking status. RESULTS: In total, 345â¯MC cases (78.6% female) and 583 matched controls (77.2% female) were included. In the univariate analyses, the percentage of urban green within a 500â¯m buffer and residential proximity to the nearest highway were associated with MC (both pâ¯<â¯0.10). On the multivariable level only a higher age at diagnosis (OR 1.02, 95%-CI 1.01-1.04) and current smoking at index date (OR 4.30; 95%-CI 3.01-6.14) were significantly associated with MC. CONCLUSION: Based on the current findings, ambient air quality does not seem to be an important risk factor for MC, in contrast to the well-known risk factors age and current smoking.
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Contaminantes Atmosféricos/análisis , Contaminación del Aire/estadística & datos numéricos , Colitis Microscópica/epidemiología , Exposición a Riesgos Ambientales/estadística & datos numéricos , Sistemas de Información Geográfica , Estudios de Casos y Controles , Femenino , Humanos , Masculino , Países Bajos/epidemiología , Factores de RiesgoRESUMEN
Background: Biomarkers that can predict the prognosis of colorectal cancer (CRC) patients and that can stratify high-risk early stage patients from low-risk early stage patients are urgently needed for better management of CRC. During the last decades, a large variety of prognostic DNA methylation markers has been published in the literature. However, to date, none of these markers are used in clinical practice. Methods: To obtain an overview of the number of published prognostic methylation markers for CRC, the number of markers that was validated independently, and the current level of evidence (LoE), we conducted a systematic review of PubMed, EMBASE, and MEDLINE. In addition, we scored studies based on the REMARK guidelines that were established in order to attain more transparency and complete reporting of prognostic biomarker studies. Eighty-three studies reporting on 123 methylation markers fulfilled the study entry criteria and were scored according to REMARK. Results: Sixty-three studies investigated single methylation markers, whereas 20 studies reported combinations of methylation markers. We observed substantial variation regarding the reporting of sample sizes and patient characteristics, statistical analyses, and methodology. The median (range) REMARK score for the studies was 10.7 points (4.5 to 17.5) out of a maximum of 20 possible points. The median REMARK score was lower in studies, which reported a p value below 0.05 versus those, which did not (p = 0.005). A borderline statistically significant association was observed between the reported p value of the survival analysis and the size of the study population (p = 0.051). Only 23 out of 123 markers (17%) were investigated in two or more study series. For 12 markers, and two multimarker panels, consistent results were reported in two or more study series. For four markers, the current LoE is level II, for all other markers, the LoE is lower. Conclusion: This systematic review reflects that adequate reporting according to REMARK and validation of prognostic methylation markers is absent in the majority of CRC methylation marker studies. However, this systematic review provides a comprehensive overview of published prognostic methylation markers for CRC and highlights the most promising markers that have been published in the last two decades.
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Biomarcadores de Tumor/genética , Neoplasias Colorrectales/genética , Metilación de ADN , Islas de CpG , Epigénesis Genética , Humanos , Pronóstico , Análisis de SupervivenciaRESUMEN
BACKGROUND: The pathophysiology of microscopic colitis (MC) is not fully understood. A dysregulation of the adaptive immune response has been hypothesized, of which the maturation and function is imprinted in early life. Various other factors (e.g., hormonal factors) have also been found to be associated, sometimes, with minimal or conflicting evidence. The aims of this study were to evaluate whether an exposure to (microbial) agents in early life might be protective for MC development and to assess the role of several less well-established risk factors in one study. METHODS: A case-control study was conducted including MC cases diagnosed in the Southern part of the Netherlands between 2000 and 2012. Cases were matched to non-MC controls from the same area, based on gender and year of birth, and assigned the same index date. All subjects filled out the same study questionnaire on various risk factors. RESULTS: In total, 171 MC cases and 361 controls were included. In the multivariable logistic regression analysis, current smoking (odds ratio 6.23, 95% confidence interval, 3.10-12.49), arthrosis, and a cardiac disorder were associated with MC. No association was observed, for example, factors related to early life exposure to microbial antigens, passive smoking, rheumatoid arthritis, celiac disease, or hormonal factors. CONCLUSIONS: Early life exposure to microbial antigens and increased hormonal exposure were not found to be protective for MC. Current smoking seems to be an incontestable risk factor for MC. Therefore, exposure to environmental risk factors later may be of relevance in MC pathogenesis and warrants further investigation.
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Enfermedad Celíaca/complicaciones , Colitis Microscópica/epidemiología , Estilo de Vida , Contaminación por Humo de Tabaco/efectos adversos , Adulto , Factores de Edad , Anciano , Estudios de Casos y Controles , Comorbilidad , Exposición a Riesgos Ambientales/efectos adversos , Femenino , Humanos , Modelos Logísticos , Masculino , Persona de Mediana Edad , Análisis Multivariante , Países Bajos/epidemiología , Factores de Riesgo , Encuestas y CuestionariosRESUMEN
The incidence of microscopic colitis (MC) in The Netherlands is increasing, yet the numbers are low compared to other countries. Awareness is likely to play a role. We describe two cases to illustrate the benefit of MC awareness among physicians and pathologists. In a 45-year-old female who presented with chronic diarrhoea, no cause could be identified despite extensive examinations in other hospitals. A biopsy revision, performed in our centre, revealed MC. Treatment with budesonide was immediately effective. A 76-year-old female with chronic diarrhoea was also diagnosed with MC. Because a relationship with NSAID use was suspected, the drug was withdrawn and the diarrhoea resolved. These cases illustrate that awareness of MC might accelerate the diagnosis of patients with chronic diarrhoea, consequently enabling the prescription of oral budesonide, a highly effective treatment. Some drugs are associated with an increased risk of MC. Withdrawal of these drugs could be another successful treatment strategy.
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Antiinflamatorios no Esteroideos/uso terapéutico , Colitis Microscópica/complicaciones , Colitis Microscópica/diagnóstico , Diarrea/etiología , Anciano , Concienciación , Biopsia , Femenino , Humanos , Incidencia , Persona de Mediana Edad , Países Bajos , Resultado del TratamientoRESUMEN
PURPOSE: Lynch syndrome colorectal cancers often lose human leukocyte antigen (HLA) class I expression. The outgrowth of clones with immune evasive phenotypes is thought to be positively selected by the action of cytotoxic T cells that target HLA class I-positive cancer cells. To investigate this hypothesis, we related the type and density of tumor lymphocytic infiltrate in Lynch colorectal cancers with their HLA class I phenotype and clinicopathologic stage. EXPERIMENTAL DESIGN: HLA class I expression was assessed by means of immunohistochemistry. Characterization of tumor-infiltrating lymphocytes was carried out by using a triple immunofluorescence procedure that allowed the simultaneous detection of CD3-, CD8-, and granzyme B (GZMB)-positive cells. Additional markers were also used for further characterization of an elusive CD3(-)/CD8(-)/GZMB(+) cell population. RESULTS: We discovered that high tumor infiltration by activated CD8(+) T cells correlated with aberrant HLA class I expression and associated with early tumor stages (P < 0.05). CD8(+) T cells were most abundant in HLA class I heterogeneous tumors (P = 0.02) and frequent in HLA class I-negative cases (P = 0.04) when compared with HLA class I-positive carcinomas. An elusive immune cell population (CD45(+)/CD8(-)/CD56(-)/GZMB(+)) was characteristic for HLA class I-negative tumors lacking lymph node metastases (P < 0.01). CONCLUSIONS: The immune system assumes an important role in counteracting the progression of Lynch colorectal cancers and in selecting abnormal HLA class I phenotypes. Our findings support the development of clinical strategies that explore the natural antitumor immune responses occurring in Lynch syndrome carriers.