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1.
J Crohns Colitis ; 2024 May 14.
Artigo em Inglês | MEDLINE | ID: mdl-38741227

RESUMO

Inflammatory bowel disease (IBD) patients are at increased risk of developing colorectal neoplasia (CRN). In this review, we aim to provide an up-to-date overview and future perspectives on CRN management in IBD. Advances in endoscopic surveillance and resection techniques have resulted in a shift towards endoscopic management of neoplastic lesions in place of surgery. Endoscopic treatment is recommended for all CRN if complete resection is feasible. Standard (cold snare) polypectomy, endoscopic mucosal resection and endoscopic submucosal dissection should be performed depending on lesion complexity (size, delineation, morphology, surface architecture, submucosal fibrosis/invasion) to maximize the likelihood of complete resection. If complete resection is not feasible, surgical treatment options should be discussed by a multidisciplinary team. While (sub)total and proctocolectomy play an important role in management of endoscopically unresectable CRN, partial colectomy may be considered in a subgroup of patients in endoscopic remission with limited disease extent without other CRN risk factors. High synchronous and metachronous CRN rates warrant careful mucosal visualization with shortened intervals for at least 5 years after treatment of CRN.

2.
Eur J Cancer ; 204: 114044, 2024 Apr 07.
Artigo em Inglês | MEDLINE | ID: mdl-38636289

RESUMO

BACKGROUND: A pathological complete response (pCR) following chemoradiation (CRT) or short-course radiotherapy (scRT) leads to a favourable prognosis in patients with rectal cancer. Total neo-adjuvant therapy (TNT) doubles the pCR rate, but it is unknown whether oncological outcomes remain favourable and whether the same characteristics are associated with pCR as after CRT. METHODS: Comparison between patients with pCR in the RAPIDO trial in the experimental [EXP] (scRT, chemotherapy, surgery, as TNT) and standard-of-care treatment [STD] (CRT, surgery, postoperative chemotherapy depending on hospital policy) groups. Primary and secondary outcomes were time-to-recurrence (TTR), overall survival (OS) and association between patient, tumour, and treatment characteristics and pCR. RESULTS: Among patients with a resection within six months after preoperative treatment, 120/423 (28%) [EXP] and 57/398 (14%) [STD] achieved a pCR. Following pCR, 5-year cumulative TTR and OS rates in the EXP and STD arms were 8% vs. 7% (hazard ratio 1.04, 95%CI 0.32-3.38) and 94% vs. 93% (hazard ratio 1.41, 95%CI 0.51-3.92), respectively. Besides the EXP treatment (odds ratio 2.70, 95%CI 1.83-3.97), pre-treatment carcinoembryonic antigen (CEA) <5, pre-treatment tumour size <40 mm and cT2 were associated with pCR. Distance from the anal verge was the only characteristic with a statistically significant difference in association with pCR between the EXP and STD treatment (Pinteraction=0.042). pCR rates did not increase with prolonged treatment time. CONCLUSIONS: The doubled pCR rate of TNT compared to CRT results in similar oncological outcomes. Characteristics associated with pCR are the EXP treatment, normal CEA, and small tumour size.

3.
Hum Pathol ; 145: 34-41, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38367815

RESUMO

The biological mechanisms and potential clinical impact of heterotopic ossification (HO) in colorectal neoplasms are not fully understood. This study investigates the clinicopathological characteristics of colorectal neoplasms associated with HO and examines the potential role of the bone morphogenetic protein (BMP) pathway in development of HO. An artificial intelligence (AI) based classification of colorectal cancers (CRC) exhibiting HO and their association with consensus molecular subtypes (CMS) is performed. The study included 77 cases via the Dutch nationwide Pathology databank. Immunohistochemistry for BMP2, SMAD4, and Osterix was performed. An AI algorithm assessed the tumour-stroma ratio to approximate the CMS. A literature search yielded 96 case reports, which were analysed and compared with our cases for clinicopathological parameters. HO was more frequently observed in our cohort in traditional serrated adenomas (25%), tubulovillous adenomas (25%) and juvenile polyps (25%), while in the literature it was most often seen in juvenile polyps (38.2%) and inflammatory polyps (29.4%). In both cohorts, carcinomas were mostly conventional (>60%) followed by mucinous and serrated adenocarcinomas. Higher expression of BMP2, SMAD4, and Osterix was observed in tumour and/or stromal cells directly surrounding bone, indicating activation of the BMP pathway. The tumour-stroma analysis appointed >50% of the cases to the mesenchymal subtype (CMS4) (59%). HO has a predilection for serrated and juvenile/inflammatory polyps, mucinous and serrated adenocarcinomas. BMP signalling is activated and seems to play a role in formation of HO in colorectal neoplasms. In line with TGFß/BMP pathway activation associated with CMS4 CRC, HO seems associated with CMS4.


Assuntos
Adenocarcinoma , Adenoma , Carcinoma , Pólipos do Colo , Neoplasias Colorretais , Ossificação Heterotópica , Humanos , Pólipos do Colo/patologia , Inteligência Artificial , Adenoma/patologia , Neoplasias Colorretais/patologia , Pólipos Intestinais
4.
Histopathology ; 84(6): 935-946, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38192084

RESUMO

AIMS: Lymph node metastases (LNM) are one of the most important prognostic indicators in solid tumours and a major component of cancer staging. Neoadjuvant therapy might influence nodal status by induction of regression. Our aim is to determine the prevalence and role of regression of LNM on outcomes in patients with rectal cancer. METHODS AND RESULTS: Four independent study populations of rectal cancer patients treated with similar regimens of chemoradiotherapy were pooled together to obtain a total cohort of 469 patients. Post-treatment nodal status (ypN) and signs of tumour regression (Reg) were incorporated to form three-tiered (ypN- Reg+, ypN- Reg- and ypN+) and four-tiered (ypN- Reg+, ypN- Reg-, ypN+ Reg+ and ypN+ Reg-) classifications. In our cohort, 31% of patients presented with ypN+ rectal cancer. As expected, we found significantly worse overall survival (OS) in ypN+ patients compared to ypN- patients (P = 0.002). The percentage of ypN- patients with lymph nodes with complete regression was 20% in our cohort. While node-negative patients with and without regression had similar OS (P = 0.09), disease-free survival (DFS) was significantly better in node-negative patients with regression (P = 0.009). CONCLUSIONS: Regression in lymph nodes is frequent, and node-negative patients with evidence of lymph node regression have better DFS compared to node-negative patients without such evidence.


Assuntos
Terapia Neoadjuvante , Neoplasias Retais , Humanos , Terapia Neoadjuvante/métodos , Linfonodos/patologia , Neoplasias Retais/patologia , Prognóstico , Estadiamento de Neoplasias , Quimiorradioterapia/métodos , Intervalo Livre de Doença , Metástase Linfática/patologia , Estudos Retrospectivos
5.
Histopathology ; 84(6): 1056-1060, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38275207

RESUMO

AIM: Currently, screening of colorectal cancers (CRC) by assessing mismatch repair deficiency (dMMR) or microsatellite instability (MSI) is used to identify Lynch syndrome (LS) patients. Advanced adenomas are considered immediate precursor lesions of CRC. In this study we investigate the relevance of screening of advanced adenomas for LS in population screening. METHODS AND RESULTS: Advanced adenomas (n = 1572) were selected from the Dutch colorectal cancer population screening programme, based on one or more of the criteria: tubulovillous (n = 848, 54%) or villous adenoma (n = 118, 7.5%), diameter ≥ 1 cm (n = 1286, 82%) and/or high-grade dysplasia (n = 176, 11%). In 86 cases (5%), all three criteria were fulfilled at the same time. MMR-IHC and/or MSI analyses were performed on all cases. Only five advanced adenomas (0.3%) showed dMMR and MSI, including two cases with hypermethylation. In at least two patients a germline event was suspected based on allelic frequencies. No pathogenic explanation was found in the last case. CONCLUSION: Timely testing of precursor lesions would be preferable to detect new LS patients before CRC development. However, standard assessment of dMMR of advanced adenomas from the population screening is not effective.


Assuntos
Adenoma , Neoplasias Encefálicas , Neoplasias Colorretais Hereditárias sem Polipose , Neoplasias Colorretais , Síndromes Neoplásicas Hereditárias , Humanos , Reparo de Erro de Pareamento de DNA/genética , Detecção Precoce de Câncer , Neoplasias Colorretais/diagnóstico , Neoplasias Colorretais/genética , Neoplasias Colorretais Hereditárias sem Polipose/diagnóstico , Neoplasias Colorretais Hereditárias sem Polipose/genética , Neoplasias Colorretais Hereditárias sem Polipose/patologia , Adenoma/diagnóstico , Adenoma/genética , Instabilidade de Microssatélites
6.
United European Gastroenterol J ; 12(3): 299-308, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38193866

RESUMO

BACKGROUND: The International Collaboration on Cancer Reporting proposes histological tumour type, lymphovascular invasion, tumour grade, perineural invasion, extent, and dimensions of invasion as risk factors for lymph node metastases and tumour progression in completely endoscopically resected pT1 colorectal cancer (CRC). OBJECTIVE: The aim of the study was to propose a predictive and reliable score to optimise the clinical management of endoscopically resected pT1 CRC patients. METHODS: This multi-centric, retrospective International Budding Consortium (IBC) study included an international pT1 CRC cohort of 565 patients. All cases were reviewed by eight expert gastrointestinal pathologists. All risk factors were reported according to international guidelines. Tumour budding and immune response (CD8+ T-cells) were assessed with automated models using artificial intelligence. We used the information on risk factors and least absolute shrinkage and selection operator logistic regression to develop a prediction model and generate a score to predict the occurrence of lymph node metastasis or cancer recurrence. RESULTS: The IBC prediction score included the following parameters: lymphovascular invasion, tumour buds, infiltration depth and tumour grade. The score has an acceptable discrimination power (area under the curve of 0.68 [95% confidence intervals (CI) 0.61-0.75]; 0.64 [95% CI 0.57-0.71] after internal validation). At a cut-off of 6.8 points to discriminate high-and low-risk patients, the score had a sensitivity and specificity of 0.9 [95% CI 0.8-0.95] and 0.26 [95% 0.22, 0.3], respectively. CONCLUSION: The IBC score is based on well-established risk factors and is a promising tool with clinical utility to support the management of pT1 CRC patients.


Assuntos
Inteligência Artificial , Neoplasias Colorretais , Humanos , Estudos Retrospectivos , Metástase Linfática , Neoplasias Colorretais/cirurgia , Neoplasias Colorretais/patologia , Recidiva Local de Neoplasia/epidemiologia
8.
BJU Int ; 133(3): 305-313, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-37877215

RESUMO

OBJECTIVES: To perform a retrospective cohort analysis for metastatic tumours in the testes to explore the timing, presentation and prognosis of this particular type of metastases and the factors that influence outcome. PATIENTS AND METHODS: A nationwide retrospective review of pathology reports of patients with pathologically confirmed metastases to the testis between 1991 and 2021 was performed. Data were collected from the Dutch nationwide pathology databank (PALGA) and the Netherlands Cancer Registry. Log-rank testing and Kaplan-Meier analyses were used to assess overall survival (OS), and Cox proportional hazard models were used for multivariate survival analysis. RESULTS: A total of 175 patients with a testicular metastasis were included. The median (range) age at diagnosis of testicular metastasis was 67 (3-88) years. Testicular metastases originated from a variety of primary tumours, although most frequently from the prostate (40.6%), kidney (13.7%), colon (10.3%), bladder (7.4%) and skin (5.7%). Synchronous testicular metastasis was detected in 53 cases, while 114 metachronous lesions were found after a median (interquartile range) interval of 22 (1-53) months after the original cancer diagnosis. OS after the diagnosis of a testicular metastasis was poor, with a median survival of 14.2 months (95% confidence interval 10.2-18.3). Primary tumour origin was an independent factor for survival, with worst survival for patients with primary skin, bladder and colon cancer. CONCLUSION: Testicular metastases are very uncommon and arise mainly from primary tumours anatomically close to the testes. Most patients develop metachronous testicular metastasis at an oligometastatic disease stage. These metastases are invariably associated with poor survival.


Assuntos
Segunda Neoplasia Primária , Neoplasias Testiculares , Masculino , Humanos , Idoso , Idoso de 80 Anos ou mais , Estudos Retrospectivos , Prognóstico , Análise de Sobrevida , Segunda Neoplasia Primária/patologia
9.
Endoscopy ; 56(1): 5-13, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37935373

RESUMO

BACKGROUND: Screen-detected colorectal cancers (CRCs) are often treated less invasively than stage-matched non-screen-detected CRCs, but the reasons for this are not fully understood. This study evaluated the treatment of stage I CRCs detected within and outside of the screening program in the Netherlands. METHODS : Data from the Netherlands Cancer Registry for all stage I CRCs diagnosed between January 1, 2008 and December 31, 2020 were analyzed, comparing patient, tumor, and treatment characteristics of screen-detected and non-screen-detected stage I CRCs. Multivariable logistic regression was used to assess the association between treatment (local excision only vs. surgical oncologic resection) and patient and tumor characteristics, stratified for T stage and tumor location. RESULTS: Screen-detected stage I CRCs were relatively more often T1 than T2 compared with non-screen-detected stage I CRCs (66.9 % vs. 53.3 %; P < 0.001). When only T1 tumors were considered, both screen-detected colon and rectal cancers were more often treated with local excision only than non-screen-detected T1 cancers (odds ratio [OR] 2.19, 95 %CI 1.93-2.49; and OR 1.29, 95 %CI 1.05-1.59, respectively), adjusted for sex, tumor location, lymphovascular invasion (LVI) status, and tumor differentiation. CONCLUSIONS : Less invasive treatment of screen-detected stage I CRC is partly explained by the higher rate of T1 cancers compared with non-screen-detected stage I CRCs. T1 stage I screen-detected CRCs were also more likely to undergo less invasive treatment than non-screen-detected CRCs, adjusted for risk factors such as LVI and tumor differentiation. Future research should investigate whether the choice of local excision was related to unidentified cancer-related factors or the expertise of the endoscopists.


Assuntos
Neoplasias Colorretais , Neoplasias Retais , Humanos , Detecção Precoce de Câncer/métodos , Neoplasias Colorretais/diagnóstico , Neoplasias Colorretais/cirurgia , Neoplasias Colorretais/patologia , Fatores de Risco , Colonoscopia
10.
Mod Pathol ; 37(1): 100376, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37926423

RESUMO

The current stratification of tumor nodules in colorectal cancer (CRC) staging is subjective and leads to high interobserver variability. In this study, the objective assessment of the shape of lymph node metastases (LNMs), extranodal extension (ENE), and tumor deposits (TDs) was correlated with outcomes. A test cohort and a validation cohort were included from 2 different institutions. The test cohort consisted of 190 cases of stage III CRC. Slides with LNMs and TDs were annotated and processed using a segmentation algorithm to determine their shape. The complexity ratio was calculated for every shape and correlated with outcomes. A cohort of 160 stage III CRC cases was used to validate findings. TDs showed significantly more complex shapes than LNMs with ENE, which were more complex than LNMs without ENE (P < .001). In the test cohort, patients with the highest sum of complexity ratios had significantly lower disease-free survival (P < .01). When only the nodule with the highest complexity was considered, this effect was even stronger (P < .001). This maximum complexity ratio per patient was identified as an independent prognostic factor in the multivariate analysis (hazard ratio, 2.47; P < .05). The trends in the validation cohort confirmed the results. More complex nodules in stage III CRC were correlated with significantly worse disease-free survival, even if only based on the most complex nodule. These results suggest that more complex nodules reflect more invasive tumor biology. As most of the more complex nodules were diagnosed as TDs, we suggest providing a more prominent role for TDs in the nodal stage and include an objective complexity measure in their definition.


Assuntos
Neoplasias Colorretais , Humanos , Prognóstico , Estadiamento de Neoplasias , Neoplasias Colorretais/patologia , Intervalo Livre de Doença , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Linfonodos/patologia
11.
Breast Cancer ; 31(2): 263-271, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38133738

RESUMO

BACKGROUND: Metastatic spread is characterized by considerable heterogeneity in most cancers. With increasing treatment options for patients with metastatic disease, there is a need for insight into metastatic patterns of spread in breast cancer patients using large-scale studies. METHODS: Records of 2622 metastatic breast cancer patients who underwent autopsy (1974-2010) were retrieved from the nationwide Dutch pathology databank (PALGA). Natural language processing (NLP) and manual information extraction (IE) were applied to identify the tumors, patient characteristics, and locations of metastases. RESULTS: The accuracy (0.90) and recall (0.94) of the NLP model outperformed manual IE (on 132 randomly selected patients). Adenocarcinoma no special type more frequently metastasizes to the lung (55.7%) and liver (51.8%), whereas, invasive lobular carcinoma mostly spread to the bone (54.4%) and liver (43.8%), respectively. Patients with tumor grade III had a higher chance of developing bone metastases (61.6%). In a subgroup of patients, we found that ER+/HER2+ patients were more likely to metastasize to the liver and bone, compared to ER-/HER2+ patients. CONCLUSION: This is the first large-scale study that demonstrates that artificial intelligence methods are efficient for IE from Dutch databanks. Different histological subtypes show different frequencies and combinations of metastatic sites which may reflect the underlying biology of metastatic breast cancer.


Assuntos
Neoplasias Ósseas , Neoplasias da Mama , Humanos , Feminino , Neoplasias da Mama/patologia , Inteligência Artificial , Neoplasias Ósseas/secundário , Autopsia , Receptor ErbB-2
13.
J Pathol ; 261(4): 401-412, 2023 12.
Artigo em Inglês | MEDLINE | ID: mdl-37792663

RESUMO

Both lymph node metastases (LNMs) and tumour deposits (TDs) are included in colorectal cancer (CRC) staging, although knowledge regarding their biological background is lacking. This study aimed to compare the biology of these prognostic features, which is essential for a better understanding of their role in CRC spread. Spatially resolved transcriptomic analysis using digital spatial profiling was performed on TDs and LNMs from 10 CRC patients using 1,388 RNA targets, for the tumour cells and tumour microenvironment. Shotgun proteomics identified 5,578 proteins in 12 different patients. Differences in RNA and protein expression were analysed, and spatial deconvolution was performed. Image-based consensus molecular subtype (imCMS) analysis was performed on all TDs and LNMs included in the study. Transcriptome and proteome profiles identified distinct clusters for TDs and LNMs in both the tumour and tumour microenvironment segment, with upregulation of matrix remodelling, cell adhesion/motility, and epithelial-mesenchymal transition (EMT) in TDs (all p < 0.05). Spatial deconvolution showed a significantly increased abundance of fibroblasts, macrophages, and regulatory T-cells (p < 0.05) in TDs. Consistent with a higher fibroblast and EMT component, imCMS classified 62% of TDs as poor prognosis subtype CMS4 compared to 36% of LNMs (p < 0.05). Compared to LNMs, TDs have a more invasive state involving a distinct tumour microenvironment and upregulation of EMT, which are reflected in a more frequent histological classification of TDs as CMS4. These results emphasise the heterogeneity of locoregional spread and the fact that TDs should merit more attention both in future research and during staging. © 2023 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.


Assuntos
Neoplasias Colorretais , Transcriptoma , Humanos , Metástase Linfática , Extensão Extranodal , Proteômica , Prognóstico , Neoplasias Colorretais/genética , Neoplasias Colorretais/patologia , RNA , Microambiente Tumoral
14.
Endoscopy ; 55(12): 1061-1069, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37793423

RESUMO

BACKGROUND: In the Dutch colorectal (CRC) screening program, fecal immunochemical test (FIT)-positive individuals are referred for colonoscopy. If no relevant findings are detected at colonoscopy, individuals are reinvited for FIT screening after 10 years. We aimed to assess CRC risk after a negative colonoscopy in FIT-positive individuals. METHODS: In this cross-sectional cohort study, data were extracted from the Dutch national screening information system. Participants with a positive FIT followed by a negative colonoscopy between 2014 and 2018 were included. A negative colonoscopy was defined as a colonoscopy during which no more than one nonvillous, nonproximal adenoma < 10 mm or serrated polyp < 10 mm was found. The main outcome was interval post-colonoscopy CRC (iPCCRC) risk. iPCCRC risk was reviewed against the risk of interval CRC after a negative FIT (FIT IC) with a 2-year screening interval. RESULTS: 35 052 FIT-positive participants had a negative colonoscopy and 24 iPCCRCs were diagnosed, resulting in an iPCCRC risk of 6.85 (95 %CI 4.60-10.19) per 10 000 individuals after a median follow-up of 1.4 years. After 2.5 years of follow-up, age-adjusted iPCCRC risk was approximately equal to FIT IC risk at 2 years. CONCLUSION: Risk of iPCCRC within a FIT-based CRC screening program was low during the first years after colonos-copy but, after 2.5 years, was the same as the risk in FIT-negative individuals at 2 years, when they are reinvited for screening. Colonoscopy quality may therefore require further improvement and FIT screening interval may need to be reduced after negative colonoscopy.


Assuntos
Adenoma , Neoplasias Colorretais , Humanos , Pré-Escolar , Neoplasias Colorretais/diagnóstico , Estudos Transversais , Detecção Precoce de Câncer/métodos , Colonoscopia , Adenoma/diagnóstico , Programas de Rastreamento/métodos , Sangue Oculto , Fezes
15.
Oncogene ; 42(38): 2816-2827, 2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-37587332

RESUMO

Computational pathology (CPath) algorithms detect, segment or classify cancer in whole slide images, approaching or even exceeding the accuracy of pathologists. Challenges have to be overcome before these algorithms can be used in practice. We therefore aim to explore international perspectives on the future role of CPath in oncological pathology by focusing on opinions and first experiences regarding barriers and facilitators. We conducted an international explorative eSurvey and semi-structured interviews with pathologists utilizing an implementation framework to classify potential influencing factors. The eSurvey results showed remarkable variation in opinions regarding attitude, understandability and validation of CPath. Interview results showed that barriers focused on the quality of available evidence, while most facilitators concerned strengths of CPath. A lack of consensus was present for multiple factors, such as the determination of sufficient validation using CPath, the preferred function of CPath within the digital workflow and the timing of CPath introduction in pathology education. The diversity in opinions illustrates variety in influencing factors in CPath adoption. A next step would be to quantitatively determine important factors for adoption and initiate validation studies. Both should include clear case descriptions and be conducted among a more homogenous panel of pathologists based on sub specialization.


Assuntos
Oncologia , Patologistas , Humanos , Algoritmos
16.
Histopathology ; 83(6): 870-879, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37609761

RESUMO

AIMS: Partial response to neoadjuvant chemoradiotherapy (CRT) presents with one of two main response patterns: shrinkage or fragmentation. This study investigated the relevance of these response patterns in rectal cancer, correlation with other response indicators, and outcome. METHODS AND RESULTS: The study included a test (n = 197) and a validation cohort (n = 218) of post-CRT patients with rectal adenocarcinoma not otherwise specified and a partial response. Response patterns were scored by two independent observers using a previously developed three-step flowchart. Tumour regression grading (TRG) was established according to both the College of American Pathologists (CAP) and Dworak classifications. In both cohorts, the predominant response pattern was fragmentation (70% and 74%), and the scoring interobserver agreement was excellent (k = 0.85). Patients with a fragmented pattern presented with significantly higher pathological stage (ypTNM II-IV, 78% versus 35%; P < 0.001), less tumour regression with Dworak (P = 0.004), and CAP TRG (P = 0.005) compared to patients with a shrinkage pattern. As a predictor of prognosis, the shrinkage pattern outperformed the TRG classification and stratified patients better in overall (fragmented pattern, hazard ratio [HR] 2.04, 95% confidence interval [CI] 1.19-3.50, P = 0.008) and disease-free survival (DFS; fragmented pattern, HR 2.50, 95% CI 1.23-5.10, P = 0.011) in the combined cohorts. The multivariable regression analyses revealed pathological stage as the only independent predictor of DFS. CONCLUSIONS: The heterogeneous nature of tumour response following CRT is reflected in fragmentation and shrinkage. In rectal cancer there is a predominance of the fragmented pattern, which is associated with advanced stage and less tumour regression. While not independently associated with survival, these reproducible patterns give insights into the biology of tumour response.


Assuntos
Quimiorradioterapia , Neoplasias Retais , Humanos , Resultado do Tratamento , Quimiorradioterapia/métodos , Prognóstico , Neoplasias Retais/patologia , Intervalo Livre de Doença , Terapia Neoadjuvante/métodos , Estadiamento de Neoplasias , Estudos Retrospectivos
17.
J Pathol ; 261(1): 19-27, 2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-37403270

RESUMO

Tumor budding (TB) is a strong biomarker of poor prognosis in colorectal cancer and other solid cancers. TB is defined as isolated single cancer cells or clusters of up to four cancer cells at the invasive tumor front. In areas with a large inflammatory response at the invasive front, single cells and cell clusters surrounding fragmented glands are observed appearing like TB. Occurrence of these small groups is referred to as pseudobudding (PsB), which arises due to external influences such as inflammation and glandular disruption. Using a combination of orthogonal approaches, we show that there are clear biological differences between TB and PsB. TB is representative of active invasion by presenting features of epithelial-mesenchymal transition and exhibiting increased deposition of extracellular matrix within the surrounding tumor microenvironment (TME), whereas PsB represents a reactive response to heavy inflammation where increased levels of granulocytes within the surrounding TME are observed. Our study provides evidence that areas with a strong inflammatory reaction should be avoided in the routine diagnostic assessment of TB. © 2023 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.


Assuntos
Neoplasias , Humanos , Transição Epitelial-Mesenquimal , Inflamação , Reino Unido , Microambiente Tumoral
18.
Eur J Cancer ; 190: 112942, 2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-37406529

RESUMO

BACKGROUND: High participation rates are essential for a screening programme to be beneficial. To reach non-participants in a targeted manner, insight in characteristics of non-participants is needed. We investigated demographic differences between participants and non-participants in the Dutch faecal immunochemical test-based colorectal cancer (CRC) screening programme. METHODS: In this population-based cohort study, we included all invitees for CRC screening in 2018 and 2019. Participation status, birth year, and sex were extracted from the Dutch national screening information system and linked to demographic characteristics from Statistics Netherlands, including migration background, level of education, socioeconomic category, household composition, and household income. A multivariable logistic regression was used to assess the association between demographic factors and participation. RESULTS: A total of 4,383,861 individuals were invited for CRC screening in 2018 and 2019, of which 3,170,349 (72.3%) participated. Individuals were less likely to participate when they were single and/or living with others (single with other residents versus couple: odds ratio [OR] 0.34, 95% confidence interval [CI]: 0.31-0.38), had a migration background (e.g. Moroccan migrant versus Dutch background: OR 0.43, 95% CI: 0.42-0.44), or had a low income (lowest versus highest quintile: OR 0.45, 95% CI: 0.44-0.45). Although to a lesser extent, non-participation was also significantly associated with being male, being younger, receiving social welfare benefits and having a low level of education. CONCLUSION: We found that individuals who were single and/or living with others, immigrants from Morocco or individuals with low income were the least likely to participate in the Dutch CRC screening programme. Targeted interventions are needed to minimise inequities in CRC screening.


Assuntos
Neoplasias Colorretais , Detecção Precoce de Câncer , Humanos , Masculino , Feminino , Estudos de Coortes , Etnicidade , Escolaridade , Neoplasias Colorretais/diagnóstico , Neoplasias Colorretais/epidemiologia , Programas de Rastreamento , Sangue Oculto
19.
Int J Surg ; 109(7): 1961-1969, 2023 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-37300890

RESUMO

BACKGROUND: Inflammatory bowel disease (IBD) patients are at increased risk of advanced neoplasia (high-grade dysplasia or colorectal cancer). The authors aimed to (1) assess synchronous and metachronous neoplasia following (sub)total or proctocolectomy, partial colectomy or endoscopic resection for advanced neoplasia in IBD, and (2) identify factors associated with treatment choice. MATERIAL AND METHODS: In this retrospective multicenter cohort study, the authors used the Dutch nationwide pathology databank (PALGA) to identify patients diagnosed with IBD and colonic advanced neoplasia (AN) between 1991 and 2020 in seven hospitals in the Netherlands. Logistic and Fine & Gray's subdistribution hazard models were used to assess adjusted subdistribution hazard ratios for metachronous neoplasia and associations with treatment choice. RESULTS: The authors included 189 patients (high-grade dysplasia n =81; colorectal cancer n =108). Patients were treated with proctocolectomy ( n =33), (sub)total colectomy ( n =45), partial colectomy ( n =56) and endoscopic resection ( n =38). Partial colectomy was more frequently performed in patients with limited disease and older age, with similar patient characteristics between Crohn's disease and ulcerative colitis. Synchronous neoplasia was found in 43 patients (25.0%; (sub)total or proctocolectomy n =22, partial colectomy n =8, endoscopic resection n =13). The authors found a metachronous neoplasia rate of 6.1, 11.5 and 13.7 per 100 patient-years after (sub)total colectomy, partial colectomy and endoscopic resection, respectively. Endoscopic resection, but not partial colectomy, was associated with an increased metachronous neoplasia risk (adjusted subdistribution hazard ratios 4.16, 95% CI 1.64-10.54, P <0.01) compared with (sub)total colectomy. CONCLUSION: After confounder adjustment, partial colectomy yielded a similar metachronous neoplasia risk compared to (sub)total colectomy. High metachronous neoplasia rates after endoscopic resection underline the importance of strict subsequent endoscopic surveillance.


Assuntos
Colite Ulcerativa , Colite , Neoplasias do Colo , Neoplasias Colorretais , Doenças Inflamatórias Intestinais , Humanos , Estudos de Coortes , Colonoscopia , Neoplasias Colorretais/patologia , Colite/etiologia , Colite/patologia , Colite/cirurgia , Colite Ulcerativa/cirurgia , Doenças Inflamatórias Intestinais/complicações , Doenças Inflamatórias Intestinais/patologia , Doenças Inflamatórias Intestinais/cirurgia , Neoplasias do Colo/cirurgia , Colectomia/efeitos adversos , Resultado do Tratamento , Estudos Retrospectivos
20.
Inflamm Bowel Dis ; 29(8): 1347-1351, 2023 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-37327081

RESUMO

Prior colorectal neoplasia is the strongest predictor of pouch neoplasia in inflammatory bowel disease, but the underlying mechanism is unknown. We observed clonality between colorectal and pouch neoplasia in 30% of patients, indicating that most pouch neoplasia develops clonally independent from prior colorectal lesions.


Assuntos
Neoplasias Colorretais , Doenças Inflamatórias Intestinais , Humanos , Estudos de Coortes , Neoplasias Colorretais/etiologia , Doenças Inflamatórias Intestinais/complicações
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