It is proximal adenomas in hereditary nonpolyposis colorectal cancer that are prone to a fast malignant transformation

Rijcken, Fleur Em; Hollema, Harry; Kleibeuker, Jan H.

doi:10.1016/s0016-5085(08)83689-x

Cited by 4 publications

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“…Colonoscopic screening at 3-year intervals is reported to decline the risk of colorectal cancer, preventing cancer deaths, and decreasing overall mortality by approximately 65% in Lynch families (19). The high incidence of colorectal cancers within 3 years of colonoscopy is reported to be an evidence that transformation from adenoma to carcinoma might be accelerated in LS (20). On the other hand, as a result of the diagnosis of advanced colorectal cancers with this screening prothocol, Lynch and some other authors recommend colonoscopy annually or at least in every 2 years (21).…”

Section: Discussionmentioning

confidence: 99%

Lynch Syndrome; A Tale of Two Cases Sharing The Same Destiny with Metachronous Tumor Development

Çakmak¹,

Gençoğlu²,

Sever³

et al. 2017

MJWBS

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Lynch syndrome (LS), is an autosomal dominant disease, accounts for approximately 1 to 2 percent of all colorectal cancers. Individuals with LS tend to develop cancers at a relatively young age and are at risk of multiple synchronous and metachronous malignancies. Several clinical criteria have been identified to assist in diagnosing LS. Subtotal or total colectomy is the procedure of choice for these patients as a result of high risk of multiplicity of lesions and metachronous tumors in time and colonoscopic surveillance is strictly recommended. Nevertheless, when the diagnosis of LS is neglected and the cancer is regarded as sporadic and treated accordingly, patients experience insufficient surgical interventions associated with metachronous malignancies, just like these two cases we report herein. The exact identification of the cases might decrease the number of misdiagnosis in this way and might decline the metachronous tumor development, with resulting in decreased morbidity, increased life quality, and improved survival. The article herein aimed to underline the importance of basic medical examination and colonoscopic surveillance that all of the clinicians dealing with cancer treatment should be aware of and the responsibility of surgical education centers on teaching the principles of cancer management to forthcoming surgeons during residancy. © 2017 Bulent Ecevit University All rights reserved. Gönderilme Tarihi: 20.11.2016 Düzeltme 02.01.2017 Kabul: 05.03.2017 Lynch Sendromu (LS) otozomal dominant bir hastalık olup tüm kolorektal kanserlerin %1-2' sini oluşturmaktadır. LS'li bireyler göreceli olarak genç yaşta kanser gelişimine yatkındır ve multipl senkron ve metakron malignite gelişme riski altındalardır. LS tanısı koymaya yardımcı birkaç klinik kriter tanımlanmıştır. Multipl lezyonlar ve metakron tümörlerin zamanla yüksek risk olması nedeniyle bu hastalar için prosedür seçimi total ya da subtotal kolektomidir ve kolonoskopik takip şiddetle önerilmektedir. Fakat LS tanısı atlandığında ve kanser sporadik olarak addedilip buna göre tedavi edildiğinde, bu sunumdaki vakalarda olduğu gibi, hastalar metakron malignitelerle ilişkili olarak yetersiz cerrahi girişimleri deneyimlemektedirler. Vakaların kesin olarak tanımlanması; bu yolla yanlış tanıların sayısını azaltacak; azalmış mortalite, artmış hayat kalitesi ve geliştirilmiş hayat beklentisi ile sonuçlanacak olan metakron tümör gelişimini azaltacaktır. Bu makalede temel muayene ve kolonoskopik takibin öneminin kanser tedavisi ile ilgilenen tüm klinisyenlerin farkında olması; ayrıca ihtisas sürecindeki cerrahlara eğitim altındayken kanser yönetiminin prensiplerini öğreten cerrahi eğitim merkezlerinin sorumluluğunun öneminin altının çizilmesi hedeflemiştir.

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Section: Discussionmentioning

confidence: 99%

Lynch Syndrome; A Tale of Two Cases Sharing The Same Destiny with Metachronous Tumor Development

Çakmak¹,

Gençoğlu²,

Sever³

et al. 2017

MJWBS

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“…Despite the efficacy of current colonoscopy, small and especially right-sided flat or serrated adenomas are notoriously difficult to detect, resulting in substantial polyp detection miss-rates of 20%-26% (2,3). Missed lesions are a main risk factor for the occurrence of interval cancers, particularly in high-risk patients such as patients with Lynch syndrome (LS) (4)(5)(6). Advanced endoscopic imaging modalities, such as narrow-band imaging, autofluorescence imaging, and chromoendoscopy, have been extensively investigated but did not show significant improvement in adenoma detection rates (7)(8)(9).…”

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confidence: 99%

Molecular Fluorescence Endoscopy Targeting Vascular Endothelial Growth Factor A for Improved Colorectal Polyp Detection

et al. 2015

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Small and flat adenomas are known to carry a high miss-rate during standard white-light endoscopy. Increased detection rate may be achieved by molecular fluorescence endoscopy with targeted nearinfrared (NIR) fluorescent tracers. The aim of this study was to validate vascular endothelial growth factor A (VEGF-A) and epidermal growth factor receptor (EGFR)-targeted fluorescent tracers during ex vivo colonoscopy with an NIR endoscopy platform. Methods: VEGF-A and EGFR expression was determined by immunohistochemistry on a large subset of human colorectal tissue samples-48 sessile serrated adenomas/polyps, 70 sporadic high-grade dysplastic adenomas, and 19 hyperplastic polyps-and tissue derived from patients with Lynch syndrome-78 low-grade dysplastic adenomas, 57 high-grade dysplastic adenomas, and 31 colon cancer samples. To perform an ex vivo colonoscopy procedure, 14 mice with small intraperitoneal EGFR-positive HCT116 luc tumors received intravenous bevacizumab-800CW (anti-VEGF-A), cetuximab-800CW (anti-EGFR), control tracer IgG-800CW, or sodium chloride. Three days later, 8 resected HCT116 luc tumors (2-5 mm) were stitched into 1 freshly resected human colon specimen and followed by an ex vivo molecular fluorescence colonoscopy procedure. Results: Immunohistochemistry showed high VEGF-A expression in 79%-96% and high EGFR expression in 51%-69% of the colorectal lesions. Both targets were significantly overexpressed in the colorectal lesions, compared with the adjacent normal colon crypts. During ex vivo molecular fluorescence endoscopy, all tumors could clearly be delineated for both bevacizumab-800CW and cetuximab-800CW tracers. Specific tumor uptake was confirmed with fluorescent microscopy showing, respectively, stromal and cell membrane fluorescence. Conclusion: VEGF-A is a promising target for molecular fluorescence endoscopy because it showed a high protein expression, especially in sessile serrated adenomas/polyps and Lynch syndrome. We demonstrated the feasibility to visualize small tumors in real time during colonoscopy using a NIR fluorescence endoscopy platform, providing the endoscopist a wide-field redflag technique for adenoma detection. Clinical studies are currently being performed in order to provide in-human evaluation of our approach.

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“…Considera-se uma lesão apresentando alto grau de instabilidade (MSI-H) se dois ou mais marcadores demonstrarem instabilidade. Tanto os adenomas quanto os pólipos hiperplásicos podem apresentar MSI (MSI-H ou MSI-L) em casos esporádicos, no contexto do HNPCC ou em pacientes com pólipos hiperplásicos (Samowitz e Slattery, 1997;Iino et al, 1999;Hawkins et al, 2000;Iino et al, 2000;Jass et al, 2000;Rashid et al, 2000;Hawkins e Ward, 2001;Rijcken, 2002;Ricciardiello et al, 2003). A instabilidade de microssatélite de alto grau (MSI-H) é rara na ausência de displasia de alto grau, sugerindo ser provável que isso seja um evento tardio, ocorrendo na transição de adenoma para carcinoma.…”

Section: Cox-2unclassified

“…Portadores da mutação do HNPCC desenvolvem seus primeiros adenomas com idade média de 42 a 43 anos (Jarvinen et al, 2000;Lindgren et al, 2002;De Jong et al, 2004). Em comparação com adenomas esporádicos, os adenomas do HNPCC são tipicamente proximais (50% vs. 26%) e apresentam mais displasia de alto grau (Rijcken et al, 2002;De Jong et al, 2004). No estudo de Rijcken (2002), 60% dos adenomas de pacientes com HNPCC são portadores de mutação com perda da expressão do hMLH1 ou hMSH2 e os adenomas que preservam as expressões dos genes são de baixo grau de displasia.…”

Section: Cox-2unclassified

“…A progressão para displasia de alto grau é mais freqüente no cólon proximal do que no distal, indicando rápida transformação para o câncer. A mutação no MMR provavelmente não inicia o desenvolvimento do adenoma, mas está presente nos estágios iniciais da tumorogênese (Rijcken et al, 2002). Alguns adenomas no HNPCC, com diâmetro de até 0,7 cm, apresentam perda da expressão da proteína do MMR, mas com displasia de baixo grau (De Jong et al, 2004) .…”

Section: Cox-2unclassified

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Estudo imunohistoquímico das expressões: hMLH1, hMSH2 e Cox-2 em pólipos do cólon

Balbinotti¹

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2007Dedico este trabalho a minha amada Silvana e aos meus adorados filhos Gabriel, Rafael, Miguel e Fernanda. AGRADECIMENTOSAo PROF. DR. PAULO SAKAI, exemplo de inspiração na minha formação médica, pelo estímulo à pesquisa, pelos ensinamentos indispensáveis, pela dedicação e amizade que sempre demonstrou em todos os momentos de nosso convívio.Ao PROF. DR. ULYSSES RIBEIRO JR. pelo seu dinamismo, seus ensinamentos no decorrer deste projeto, atuando como co-orientador sem medir esforços, sempre disponível com seu ânimo contagiante que ficaria impossível a conclusão deste estudo sem sua participação inestimável.

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It is proximal adenomas in hereditary nonpolyposis colorectal cancer that are prone to a fast malignant transformation

Cited by 4 publications

References 0 publications

Lynch Syndrome; A Tale of Two Cases Sharing The Same Destiny with Metachronous Tumor Development

Lynch Syndrome; A Tale of Two Cases Sharing The Same Destiny with Metachronous Tumor Development

Molecular Fluorescence Endoscopy Targeting Vascular Endothelial Growth Factor A for Improved Colorectal Polyp Detection

Estudo imunohistoquímico das expressões: hMLH1, hMSH2 e Cox-2 em pólipos do cólon

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