Search

Your search keyword '"Jansen, Marnix"' showing total 438 results
Start Over Author "Jansen, Marnix"
438 results on '"Jansen, Marnix"'

152. Undifferentiated Sarcomas Develop Through Distinct Evolutionary Pathways

Author

Steele, Christopher D., primary, Tarabichi, Maxime, additional, Alexandrov, Ludmil B., additional, Oukrif, Dahmane, additional, Ye, Hongtao, additional, Fittall, Matthew, additional, Lombard, Patrick, additional, Martincorena, Inigo, additional, Tarpey, Patrick S., additional, Collord, Grace, additional, Strauss, Sandra J., additional, Berisha, Fitim, additional, Jansen, Marnix, additional, Behjati, Sam, additional, Amary, M Fernanda, additional, Tirabosco, Roberto, additional, Campbell, Peter J., additional, Van Loo, Peter, additional, Flanagan, Adrienne M., additional, and Pillay, Nischalan, additional

Published
2018
Full Text
View/download PDF

153. Robust RNA-based in situ mutation detection delineates colorectal cancer subclonal evolution

Author

Baker, Ann-Marie, primary, Huang, Weini, additional, Wang, Xiao-Ming Mindy, additional, Jansen, Marnix, additional, Ma, Xiao-Jun, additional, Kim, Jeffrey, additional, Anderson, Courtney M., additional, Wu, Xingyong, additional, Pan, Liuliu, additional, Su, Nan, additional, Luo, Yuling, additional, Domingo, Enric, additional, Heide, Timon, additional, Sottoriva, Andrea, additional, Lewis, Annabelle, additional, Beggs, Andrew D., additional, Wright, Nicholas A., additional, Rodriguez-Justo, Manuel, additional, Park, Emily, additional, Tomlinson, Ian, additional, and Graham, Trevor A., additional

Published
2017
Full Text
View/download PDF

154. Analysis of clonal expansions through the normal and premalignant human breast epithelium reveals the presence of luminal stem cells

Author

Cereser, Biancastella, primary, Jansen, Marnix, additional, Austin, Emily, additional, Elia, George, additional, McFarlane, Taneisha, additional, van Deurzen, Carolien HM, additional, Sieuwerts, Anieta M, additional, Daidone, Maria G, additional, Tadrous, Paul J, additional, Wright, Nicholas A, additional, Jones, Louise, additional, and McDonald, Stuart AC, additional

Published
2017
Full Text
View/download PDF

155. Vitamin D3 suppresses morphological evolution of the cribriform cancerous phenotype

Author

Deevi, Ravi K., McClements, Jane, McCloskey, Karen D., Fatehullah, Aliya, Tkocz, Dorota, Javadi, Arman, Higginson, Robyn, Marsh Durban, Victoria, Jansen, Marnix, Clarke, Alan, Loughrey, Maurice B., and Campbell, Frederick C.

Subjects
RC0254
Abstract

Development of cribriform morphology (CM) heralds malignant change in human colon but lack of mechanistic understanding hampers preventive therapy. This study investigated CM pathobiology in three-dimensional (3D) Caco-2 culture models of colorectal glandular architecture, assessed translational relevance and tested effects of 1,25(OH)2D3, the active form of vitamin D. CM evolution was driven by oncogenic perturbation of the apical polarity (AP) complex comprising PTEN, CDC42 and PRKCZ (phosphatase and tensin homolog, cell division cycle 42 and protein kinase C zeta). Suppression of AP genes initiated a spatiotemporal cascade of mitotic spindle misorientation, apical membrane misalignment and aberrant epithelial configuration. Collectively, these events promoted “Swiss cheese-like” cribriform morphology (CM) comprising multiple abnormal “back to back” lumens surrounded by atypical stratified epithelium, in 3D colorectal gland models. Intestinal cancer driven purely by PTEN-deficiency in transgenic mice developed CM and in human CRC, CM associated with PTEN and PRKCZ readouts. Treatment of PTEN-deficient 3D cultures with 1,25(OH)2D3 upregulated PTEN, rapidly activated CDC42 and PRKCZ, corrected mitotic spindle alignment and suppressed CM development. Conversely, mutationally-activated KRAS blocked 1,25(OH)2D3 rescue of glandular architecture. We conclude that 1,25(OH)2D3 upregulates AP signalling to reverse CM in a KRAS wild type (wt), clinically predictive CRC model system. Vitamin D could be developed as therapy to suppress inception or progression of a subset of colorectal tumors.

Published
2016

158. Abstract 3953: Visualization of treatment resistant subclones in colorectal cancer by mutation specific RNA in situ hybridization

Author

Baker, Ann-Marie, primary, Wang, Mindy, additional, Ma, Xiao-Jun, additional, Anderson, Courtney, additional, Huang, Weini, additional, Domingo, Enric, additional, Lewis, Annabelle, additional, Bridgewater, John, additional, Jansen, Marnix, additional, Wright, Nicholas A., additional, Rodriguez-Justo, Manuel, additional, Park, Emily, additional, Tomlinson, Ian, additional, and Graham, Trevor A., additional

Published
2017
Full Text
View/download PDF

160. Multi-Region Exome Sequencing Reveals the Clonal Evolution of Colitis-Associated Colorectal Cancer

Author

Baker, Ann-Marie, primary, Choi, Chang Ho R., additional, Davis, Hayley, additional, Al-Bakir, Ibrahim, additional, Martinez, Pierre, additional, Temko, Daniel, additional, Cross, William, additional, Williams, Marc, additional, Biswas, Sujata, additional, McDonald, Stuart A., additional, Wright, Nicholas A., additional, Tomlinson, Ian, additional, Moorghen, Morgan, additional, Hayes, Stephen, additional, Rodriguez-Justo, Manuel, additional, Silver, Andrew, additional, Wang, Lai Mun, additional, Jansen, Marnix, additional, Hart, Ailsa, additional, Leedham, Simon, additional, and Graham, Trevor A., additional

Published
2017
Full Text
View/download PDF

161. Practical and Robust Identification of Molecular Subtypes in Colorectal Cancer by Immunohistochemistry

Author

Trinh, Anne, primary, Trumpi, Kari, additional, De Sousa E Melo, Felipe, additional, Wang, Xin, additional, de Jong, Joan H., additional, Fessler, Evelyn, additional, Kuppen, Peter J.K., additional, Reimers, Marlies S., additional, Swets, Marloes, additional, Koopman, Miriam, additional, Nagtegaal, Iris D., additional, Jansen, Marnix, additional, Hooijer, Gerrit K.J., additional, Offerhaus, George J.A., additional, Kranenburg, Onno, additional, Punt, Cornelis J., additional, Medema, Jan Paul, additional, Markowetz, Florian, additional, and Vermeulen, Louis, additional

Published
2017
Full Text
View/download PDF

164. TGFβ signaling directs serrated adenomas to the mesenchymal colorectal cancer subtype

Author

Fessler, Evelyn, primary, Drost, Jarno, additional, Hooff, Sander R, additional, Linnekamp, Janneke F, additional, Wang, Xin, additional, Jansen, Marnix, additional, De Sousa E Melo, Felipe, additional, Prasetyanti, Pramudita R, additional, IJspeert, Joep EG, additional, Franitza, Marek, additional, Nürnberg, Peter, additional, Noesel, Carel JM, additional, Dekker, Evelien, additional, Vermeulen, Louis, additional, Clevers, Hans, additional, and Medema, Jan Paul, additional

Published
2016
Full Text
View/download PDF

165. Bcl-2 is a critical mediator of intestinal transformation

Author

van der Heijden, Maartje, primary, Zimberlin, Cheryl D., additional, Nicholson, Anna M., additional, Colak, Selcuk, additional, Kemp, Richard, additional, Meijer, Sybren L., additional, Medema, Jan Paul, additional, Greten, Florian R., additional, Jansen, Marnix, additional, Winton, Douglas J., additional, and Vermeulen, Louis, additional

Published
2016
Full Text
View/download PDF

167. Evolutionary history of human colitis-associated colorectal cancer

Author

Baker, Ann-Marie, Cross, William, Curtius, Kit, Al Bakir, Ibrahim, Choi, Chang-Ho Ryan, Davis, Hayley Louise, Temko, Daniel, Biswas, Sujata, Martinez, Pierre, Williams, Marc J, Lindsay, James O, Feakins, Roger, Vega, Roser, Hayes, Stephen J, Tomlinson, Ian P M, McDonald, Stuart A C, Moorghen, Morgan, Silver, Andrew, East, James E, Wright, Nicholas A, Wang, Lai Mun, Rodriguez-Justo, Manuel, Jansen, Marnix, Hart, Ailsa L, Leedham, Simon J, and Graham, Trevor A

Abstract

ObjectiveIBD confers an increased lifetime risk of developing colorectal cancer (CRC), and colitis-associated CRC (CA-CRC) is molecularly distinct from sporadic CRC (S-CRC). Here we have dissected the evolutionary history of CA-CRC using multiregion sequencing.DesignExome sequencing was performed on fresh-frozen multiple regions of carcinoma, adjacent non-cancerous mucosa and blood from 12 patients with CA-CRC (n=55 exomes), and key variants were validated with orthogonal methods. Genome-wide copy number profiling was performed using single nucleotide polymorphism arrays and low-pass whole genome sequencing on archival non-dysplastic mucosa (n=9), low-grade dysplasia (LGD; n=30), high-grade dysplasia (HGD; n=13), mixed LGD/HGD (n=7) and CA-CRC (n=19). Phylogenetic trees were reconstructed, and evolutionary analysis used to reveal the temporal sequence of events leading to CA-CRC.Results10/12 tumours were microsatellite stable with a median mutation burden of 3.0 single nucleotide alterations (SNA) per Mb, ~20% higher than S-CRC (2.5 SNAs/Mb), and consistent with elevated ageing-associated mutational processes. Non-dysplastic mucosa had considerable mutation burden (median 47 SNAs), including mutations shared with the neighbouring CA-CRC, indicating a precancer mutational field. CA-CRCs were often near triploid (40%) or near tetraploid (20%) and phylogenetic analysis revealed that copy number alterations (CNAs) began to accrue in non-dysplastic bowel, but the LGD/HGD transition often involved a punctuated ‘catastrophic’ CNA increase.ConclusionsEvolutionary genomic analysis revealed precancer clones bearing extensive SNAs and CNAs, with progression to cancer involving a dramatic accrual of CNAs at HGD. Detection of the cancerised field is an encouraging prospect for surveillance, but punctuated evolution may limit the window for early detection.

Published
2019
Full Text
View/download PDF

169. Stromal Indian Hedgehog Signaling Is Required for Intestinal Adenoma Formation in Mice

Author

Büller, Nikè V.J.A., primary, Rosekrans, Sanne L., additional, Metcalfe, Ciara, additional, Heijmans, Jarom, additional, van Dop, Willemijn A., additional, Fessler, Evelyn, additional, Jansen, Marnix, additional, Ahn, Christina, additional, Vermeulen, Jacqueline L.M., additional, Westendorp, B. Florien, additional, Robanus-Maandag, Els C., additional, Offerhaus, G. Johan, additional, Medema, Jan Paul, additional, D’Haens, Geert R.A.M., additional, Wildenberg, Manon E., additional, de Sauvage, Frederic J., additional, Muncan, Vanesa, additional, and van den Brink, Gijs R., additional

Published
2015
Full Text
View/download PDF

170. Is it justified to ablate flat-type esophageal squamous cancer? An analysis of endoscopic submucosal dissection specimens of lesions meeting the selection criteria of radiofrequency studies

Author

Jansen, Marnix, primary, Schölvinck, Dirk W., additional, Kushima, Ryoji, additional, Sekine, Shigeki, additional, Weusten, Bas L.A.M., additional, Wang, Guiqi Q., additional, Fleischer, David E., additional, Yoshinaga, Shigetaka, additional, Dawsey, Sanford M., additional, Meijer, Sybren L., additional, Bergman, Jacques J.G.H.M., additional, and Oda, Ichiro, additional

Published
2014
Full Text
View/download PDF

173. Tu1833 - Multi-Region Exome Sequencing Reveals the Clonal Evolution of Colitis-Associated Colorectal Cancer

Author

Baker, Ann-Marie, Choi, Chang Ho R., Davis, Hayley, Al-Bakir, Ibrahim, Martinez, Pierre, Temko, Daniel, Cross, William, Williams, Marc, Biswas, Sujata, McDonald, Stuart A., Wright, Nicholas A., Tomlinson, Ian, Moorghen, Morgan, Hayes, Stephen, Rodriguez-Justo, Manuel, Silver, Andrew, Wang, Lai Mun, Jansen, Marnix, Hart, Ailsa, Leedham, Simon, and Graham, Trevor A.

Published
2017
Full Text
View/download PDF

175. Quantification of Crypt and Stem Cell Evolution in the Normal and Neoplastic Human Colon

Author

Baker, Ann-Marie, primary, Cereser, Biancastella, additional, Melton, Samuel, additional, Fletcher, Alexander G., additional, Rodriguez-Justo, Manuel, additional, Tadrous, Paul J., additional, Humphries, Adam, additional, Elia, George, additional, McDonald, Stuart A.C., additional, Wright, Nicholas A., additional, Simons, Benjamin D., additional, Jansen, Marnix, additional, and Graham, Trevor A., additional

Published
2014
Full Text
View/download PDF

176. Tu1321 Is It Justified to Ablate Flat Type Esophageal Squamous Cancer? an Analysis of Endoscopic Submucosal Dissection Specimens of Lesions Meeting the Selection Criteria of Radiofrequency Studies

Author

SchöLvinck, Dirk, primary, Jansen, Marnix, additional, Kushima, Ryoji, additional, Sekine, Shigeki, additional, Weusten, Bas L., additional, Wang, Guiqi, additional, Fleischer, David E., additional, Yoshinaga, Shigetaka, additional, Dawsey, Sanford M., additional, Meijer, Sybren L., additional, Bergman, Jacques J., additional, and ODA, Ichiro, additional

Published
2014
Full Text
View/download PDF

177. 279 The Stem Cell Organization, and the Proliferative and Gene Expression Profile of Barrett's Epithelium, Indicates Its Origin From Gastric Glands

Author

Lavery, Danielle L., primary, Nicholson, Anna M., additional, Barr, Hugh, additional, Gay, Laura J., additional, Jeffery, Rosemary, additional, Poulsom, Richard, additional, Harrison, Rebecca F., additional, Jankowski, Janusz A., additional, Jansen, Marnix, additional, Novelli, Marco, additional, McDonald, Stuart A., additional, Rodriguez-Justo, Manuel, additional, Shepherd, Neil A., additional, and Wright, Nicholas A., additional

Published
2013
Full Text
View/download PDF

178. Inflammation Aggravates Disease Severity in Marfan Syndrome Patients

Author

Radonic, Teodora, primary, de Witte, Piet, additional, Groenink, Maarten, additional, de Waard, Vivian, additional, Lutter, Rene, additional, van Eijk, Marco, additional, Jansen, Marnix, additional, Timmermans, Janneke, additional, Kempers, Marlies, additional, Scholte, Arthur J., additional, Hilhorst-Hofstee, Yvonne, additional, van den Berg, Maarten P., additional, van Tintelen, J. Peter, additional, Pals, Gerard, additional, Baars, Marieke J. H., additional, Mulder, Barbara J. M., additional, and Zwinderman, Aeilko H., additional

Published
2012
Full Text
View/download PDF

179. Aberrant intestinal stem cell lineage dynamics in Peutz–Jeghers syndrome and familial adenomatous polyposis consistent with protracted clonal evolution in the crypt

Author

Langeveld, Danielle, primary, Jansen, Marnix, additional, de Boer, D V, additional, van Sprundel, Mariska, additional, Brosens, Lodewijk A A, additional, Morsink, Folkert H, additional, Giardiello, Francis M, additional, Offerhaus, G Johan A, additional, and de Leng, Wendy W J, additional

Published
2011
Full Text
View/download PDF

180. Diversity Counts

Author

Langeveld, Danielle, primary, Jansen, Marnix, additional, Brosens, Lodewijk, additional, Morsink, Folkert, additional, Offerhaus, G. Johan, additional, and de Leng, Wendy, additional

Published
2011
Full Text
View/download PDF

187. Barrett oesophagus: lessons on its origins from the lesion itself

Author

McDonald, Stuart A. C., Lavery, Danielle, Wright, Nicholas A., and Jansen, Marnix

Abstract

Barrett oesophagus develops when the lower oesophageal squamous epithelium is replaced with columnar epithelium, which shows both intestinal and gastric differentiation. No consensus has been reached on the origin of Barrett oesophagus. Theories include a direct origin from the oesophageal-stratified squamous epithelium, or by proximal migration of the gastric cardiac epithelium with subsequent intestinalization. Variations of this theory suggest the origin is a distinctive cell at the squamocolumnar junction, the oesophageal gland ducts, or circulating bone-marrow-derived cells. Much of the supporting evidence comes from experimental models and not from studies of Barrett mucosa. In this Perspectives article, we look at the Barrett lesion itself: at its phenotype, its complexity, its clonal architecture and its stem cell organization. We conclude that Barrett glands are unique structures, but share many similarities with gastric glands undergoing the process of intestinal metaplasia. We conclude that current evidence most strongly supports an origin from stem cells in the cardia.

Published
2015
Full Text
View/download PDF

188. Aberrant intestinal stem cell lineage dynamics in PeutzeJeghers syndrome and familial adenomatous polyposis consistent with protracted clonal evolution in the crypt.

Author

Langeveld, Danielle, Jansen, Marnix, de Boer, D. V., van Sprundel, Mariska, Brosens, Lodewijk A. A., Morsink, Folkert H., Giardiello, Francis M., Offerhaus, G. Johan A., and de Leng, Wendy W. J.

Subjects
*GENETIC disorders, *INTESTINAL physiology, *ECTOPIC tissue, *STEM cells, *DISEASE susceptibility, *CANCER genetics, *HOMEOBOX genes, *METHYLATION
Abstract

Objective Genetic predisposition to cancer in PeutzeJeghers syndrome (PJS) and the role of germline serineethreonine kinase (LKB1) mutations are poorly understood. The authors studied the effect of germline LKB1 mutations on intestinal stem cell dynamics in unaffected flat PJS mucosa. Recent research has documented that the intestinal crypt houses multiple equipotent stem cell lineages. Lineages continuously compete through random drifts, while somatically inherited methylation patterns record clonal diversity. Design To study the effect of germline LKB1 mutations on clonal expansion, the authors performed quantitative analyses of cardiac-specific homeobox methylation pattern diversity in crypts isolated from unaffected colonic mucosa obtained from archival PJS patient material. The authors compared methylation density and methylation pattern diversity in patients with PJS to those in patients with familial adenomatous polyposis and age-matched controls. Results The percentage of total methylation is comparable between groups, but the number of unique methylation patterns is significantly increased for patients with familial adenomatous polyposis and patients with PJS compared to control subjects. Conclusions Monoallelic LKB1 loss is not silent and provokes a protracted clonal evolution in the crypt. The increased methylation pattern diversity observed in unaffected PJS mucosa predicts that premalignant lesions will arise at an accelerated pace compared to the general population. INSET: Significance of this study. [ABSTRACT FROM AUTHOR]

Published
2012
Full Text
View/download PDF

189. LKB1 as the ghostwriter of crypt history.

Author

Jansen, Marnix, Langeveld, Danielle, Leng, Wendy, Milne, Anya, Giardiello, Francis, and Offerhaus, G.

Abstract

Familial cancer syndromes present rare insights into malignant tumor development. The molecular background of polyp formation and the cancer prone state in Peutz-Jeghers syndrome remain enigmatic to this day. Previously, we proposed that Peutz-Jeghers polyps are not pre-malignant lesions, but an epiphenomenon to the malignant condition. However, Peutz-Jeghers polyp formation and the cancer-prone state must both be accounted for by the same molecular mechanism. Our contribution focuses on the histopathology of the characteristic Peutz-Jeghers polyp and recent research on stem cell dynamics and how these concepts relate to Peutz-Jeghers polyposis. We discuss a protracted clonal evolution scenario in Peutz-Jeghers syndrome due to a germline LKB1 mutation. Peutz-Jeghers polyp formation and malignant transformation are separately mediated through the same molecular mechanism played out on different timescales. Thus, a single mechanism accounts for the development of benign Peutz-Jeghers polyps and for malignant transformation in Peutz-Jeghers syndrome. [ABSTRACT FROM AUTHOR]

Published
2011
Full Text
View/download PDF

191. Extension of early esophageal squamous cell neoplasia into ducts and submucosal glands and the role of endoscopic ablation therapy.

Author

Overwater, Anouk, van Munster, Sanne N., Offerhaus, G. Johan A., Seldenrijk, Cees A., Raicu, G. Mihaela, Koch, Arjun D., Bergman, Jacques J.G. H.M., Pouw, Roos E., Brosens, Lodewijk A.A., Jansen, Marnix, and Weusten, Bas L.A. M.

Abstract

Early esophageal squamous cell neoplasia (ESCN) is preferably treated with en-bloc endoscopic resection. Ablation might be an alternative for flat ESCN, but ESCN extension along the epithelial lining of ducts and submucosal glands (SMGs) might jeopardize ablation efficacy. Clinical studies suggest that local recurrence might arise from such buried ESCN niches after ablation. We studied human endoscopic resection specimens of ESCN to quantify ESCN extension into ducts/SMGs and performed a prospective porcine study to evaluate the depth of radiofrequency ablation (RFA) and CryoBalloon ablation (CBA) into ducts/SMGs. Endoscopic submucosal dissection specimens of flat-type ESCN from a Japanese (n = 65) and Dutch cohort (n = 14) were evaluated for presence and neoplastic involvement of ducts/SMGs. Twenty-seven pigs were treated with circumferential RFA (c-RFA; n = 4), focal CBA (n = 20), and focal RFA (n = 3) with 4, 60, and 9 treatment areas, respectively. After prespecified survival periods (0 hours, 8 hours, 2 days, 5 days, and 28 days), treatment areas were evaluated for uniformity and depth of ablation and affected SMGs. Neoplastic extension in ducts/SMGs was observed in most lesions: 58% (38/65) in the Japanese and 64% (9/14) in the Dutch cohort. In the animal study, 33% of SMGs (95% confidence interval, 28-50) were not affected after c-RFA, although the overlying epithelium was ablated. Focal RFA and CBA resulted in uniform ablations with effective treatment of all SMGs. ESCN extends into ducts/SMGs in most patients. In an animal model, focal RFA and CBA effectively ablated SMGs, whereas c-RFA inadequately ablated SMGs. Given this potential reason for recurrence, endoscopic resection should remain the standard of care. [ABSTRACT FROM AUTHOR]

Published
2021
Full Text
View/download PDF

193. Epithelial-Specific Loss of PTENResults in Colorectal Juvenile Polyp Formation and Invasive Cancer

Author

Marsh Durban, Victoria, Jansen, Marnix, Davies, Emma J., Morsink, Folkert H., Offerhaus, G. Johan A., and Clarke, Alan R.

Abstract

Cowden syndrome (CS) is a rare autosomal dominant cancer-prone disorder caused by germ-line mutation of the phosphatase and tensin homolog mutated on chromosome 10 (PTEN) tumor-suppressor gene. Affected patients commonly develop juvenile polyps, and show an elevated risk of developing colorectal cancers. The etiology of these peculiar polyps remains unclear, although previous work has suggested somatic PTENalterations in the stroma of juvenile polyps. After a long latency period, we find epithelial-specific PTENdeletion to cause formation of juvenile polyps in the colorectum without stromal PTENloss. More important, we find that these lesions closely recapitulate all of the characteristic histopathological features of juvenile polyps seen in patients with CS, including stromal alterations and dysplastic transformation to colorectal carcinoma. The stromal alterations we identify after epithelial-specific PTENloss suggest that PTENmay be involved in altered epithelial-mesenchymal cross talk, which, in turn, predisposes to colorectal neoplasia and polyposis. Our transgenic model is the first to recapitulate colorectal juvenile polyposis in patients with CS. We conclude that stromal PTENloss is not a prerequisite for the formation of juvenile polyps, and that colorectal juvenile polyps in CS are bona fide neoplastic precursor lesions.

Published
2014
Full Text
View/download PDF

194. Risk of metastasis among patients diagnosed with high-risk T1 esophageal adenocarcinoma who underwent endoscopic follow-up.

Author

Norton, Benjamin Charles, Aslam, Nasar, Telese, Andrea, Papaefthymiou, Apostolis, Singh, Shilpi, Sehgal, Vinay, Mitchison, Miriam, Jansen, Marnix, Banks, Matthew, Graham, David, and Haidry, Rehan

Subjects
*LYMPHATIC metastasis, *PRESERVATION of organs, tissues, etc., *ENDOSCOPIC surgery, *MEDICAL records, *LYMPH nodes
Abstract

Esophagectomy and lymphadenectomy have been the standard of care for patients at high risk (HR) of lymph node metastasis following a diagnosis of early esophageal adenocarcinoma (OAC) after endoscopic resection (ER). However, recent cohorts suggest lymph node metastasis risk is lower than initially estimated, suggesting organ preservation with close endoscopic follow-up is a viable option. We report on the 3- and 5-year risk of lymph node/distant metastasis among patients diagnosed with early HR-T1 OAC undergoing endoscopic follow-up. Patients diagnosed with HR-T1a or T1b OAC following ER at a tertiary referral center were identified and retrospectively analyzed from clinical records between 2010 and 2021. Patients were included if they underwent endoscopic follow-up after resection and were divided into HR-T1a, low risk (LR)-T1b and HR-T1b cohorts. After ER, 47 patients underwent endoscopic follow-up for early HR OAC. In total, 39 patients had an R0 resection with a combined 3- and 5-year risk of LN/distant metastasis of 6.9% [95% confidence interval (CI): 1.8–25] and 10.9% (95% CI, 3.6–30.2%), respectively. There was no significant difference when stratifying by histopathological subtype (P  = 0.64). Among those without persistent luminal disease on follow-up, the 5-year risk was 4.1% (95% CI, 0.6–26.1). Two patients died secondary to OAC with an all-cause 5-year survival of 57.5% (95% CI, 39.5–71.9). The overall risk of LN/distant metastasis for early HR T1 OAC was lower than historically reported. Endoscopic surveillance can be a reasonable approach in highly selected patients with an R0 resection and complete luminal eradication, but clear, evidence-based surveillance guidelines are needed. [ABSTRACT FROM AUTHOR]

Published
2024
Full Text
View/download PDF

195. Vertical tumor-positive resection margins and the risk of residual neoplasia after endoscopic resection of Barrett's neoplasia: a nationwide cohort with pathology reassessment.

Author

van Tilburg, Laurelle, Verheij, Eva P. D., van de Ven, Steffi E. M., van Munster, Sanne N., Weusten, Bas L. A. M., Herrero, Lorenza Alvarez, Nagengast, Wouter B., Schoon, Erik J., Alkhalaf, Alaa, Bergman, Jacques J. G. H. M., Pouw, Roos E., Oudijk, Lindsey, Meijer, Sybren L., Jansen, Marnix, Doukas, Michail, Koch, Arjun D., Brosens, Lodewijk A. A., Curvers, Wouter L., Houben, Martin H. M. G., and de Jonge, Pieter Jan F.

Subjects
*ENDOSCOPIC surgery, *SURGICAL margin, *SURGICAL excision, *CANCER cells, *TUMORS
Abstract

Background This study evaluated the proportion of patients with residual neoplasia after endoscopic resection (ER) for Barrett's neoplasia with confirmed tumor-positive vertical resection margin (R1v). Methods This retrospective cohort study included patients undergoing ER for Barrett's neoplasia with histologically documented R1v since 2008 in the Dutch Barrett Expert Centers. We defined R1v as cancer cells touching vertical resection margins and Rx as nonassessable margins. Reassessment of R1v specimens was performed by experienced pathologists until consensus was reached regarding vertical margins. Results 101/110 included patients had macroscopically complete resections (17 T1a, 84 T1b), and 99/101 (98%) ER specimens were histologically reassessed, with R1v confirmed in 74 patients (75%), Rx in 16%, and R0 in 9%. Presence/absence of residual neoplasia could be assessed in 66/74 patients during endoscopic reassessment (52) and/or in the surgical resection specimen (14), and 33/66 (50%) had residual neoplasia. Residual neoplasia detected during endoscopy was always endoscopically visible and biopsies from a normal-appearing ER scar did not detect additional neoplasia. Of 25 patients who underwent endoscopic follow-up (median 37 months [interquartile range 12–50]), 4 developed local recurrence (16.0%), all detected as visible abnormalities. Conclusions After ER with R1v, 50% of patients had no residual neoplasia. Histological evaluation of ER margins appears challenging, as in this study 75% of documented R1v cases were confirmed during reassessment. Endoscopic reassessment 8–12 weeks after ER seems to accurately detect residual neoplasia and can help to determine the most appropriate strategy for patients with R1v. [ABSTRACT FROM AUTHOR]

Published
2024
Full Text
View/download PDF

196. Analysis of LKB1mutations and other molecular alterations in pancreatic acinar cell carcinoma

Author

de Wilde, Roeland F, Ottenhof, Niki A, Jansen, Marnix, Morsink, Folkert H M, de Leng, Wendy W J, Offerhaus, G Johan A, and Brosens, Lodewijk A A

Abstract

Acinar cell carcinoma is a rare non-ductal neoplasm of the pancreas with poorly defined molecular genetic features. Recently, biallelic inactivation of LKB1was described in an acinar cell carcinoma of a Peutz-Jeghers patient carrying a heterozygous germline LKB1mutation, and inhibition of mTOR signaling resulted in partial remission of the tumor. To explore the potential of mTOR inhibitors in sporadic acinar cell carcinoma, the LKB1gene was investigated in five sporadic acinar cell carcinomas by sequence analysis, methylation analysis and mRNA expression. In addition, microsatellite instability and methylation of a number of tumor suppressor genes were investigated and KRAS, TP53, CDKN1A, SMAD4 and CTNNB1 were studied by mutation analysis and immunohistochemistry. No mutations, deletions or promoter hypermethylation of LKB1were found in any of the sporadic acinar cell carcinomas, and mRNA expression of LKB1was not altered. Amplifications at chromosome 20q and 19p were found in 100 and 80% of the cases, respectively. In addition, hypermethylation of one or more tumor suppressor genes was found in 80% of cases. One case harbored a TP53mutation, and expression of SMAD4 and CTNNB1 was altered in one case each. No KRASmutations or microsatellite instability were found. To conclude, no evidence for a role for LKB1in tumorigenesis of sporadic pancreatic acinar cell carcinoma was found. However, copy number variations and hypermethylation were found in a majority of cases. Molecular pathways involved in acinar cell carcinoma-tumorigenesis differ from those involved in ductal pancreatic neoplasms. Further studies are needed to increase our understanding of molecular pathogenesis of acinar cell carcinoma, which may eventually result in development of new therapeutic targets.

Published
2011
Full Text
View/download PDF

197. Gastrointestinal Polyposis Syndromes

Author

A.A.Brosens, Lodewijk, Hattem, W. Arnout van, Jansen, Marnix, Leng, Wendy W.J. de, Giardiello, Francis M., and Offerhaus, G. Johan A.

Abstract

Colorectal cancer is one of the leading causes of cancer-related death in the Western society, and the incidence is rising. Rare hereditary gastrointestinal polyposis syndromes that predispose to colorectal cancer have provided a model for the investigation of cancer initiation and progression in the general population. Many insights in the molecular genetic basis of cancer have emerged from the study of these syndromes. This review discusses the genetics and clinical manifestations of the three most common syndromes with gastrointestinal polyposis and an increased risk of colorectal cancer: familial adenomatous polyposis (FAP), juvenile polyposis (JP) and Peutz- Jeghers syndrome (PJS).

Published
2007

198. Overexpression of S100A4in Pancreatic Ductal Adenocarcinomas Is Associated with Poor Differentiation and DNA Hypomethylation

Author

Rosty, Christophe, Ueki, Takashi, Argani, Pedram, Jansen, Marnix, Yeo, Charles J., Cameron, John L., Hruban, Ralph H., and Goggins, Michael

Abstract

Using the National Center for Biotechnology Information Serial Analysis of Gene Expression database, we found that S100A4, a calcium-binding protein previously implicated in metastasis, was expressed in five of seven pancreatic carcinoma libraries but not in the two normal pancreatic duct libraries. We confirmed the overexpression of S100A4 using reverse transcriptase-polymerase chain reaction, which demonstrated that 18 of 19 (95%) pancreatic carcinoma cell lines expressed S100A4. Using immunohistochemistry, we found that 57 of 61 invasive pancreatic carcinomas (93%), 3 of 18 high-grade pancreatic intraepithelial neoplasia lesions (17%), and 0 of the 69 low-grade pancreatic intraepithelial neoplasia lesions expressed S100A4 protein, whereas normal pancreatic tissue and tissue affected by chronic pancreatitis did not label. Expression of S100A4 was associated with poor differentiation of the pancreatic adenocarcinomas (P= 0.001). We found that three CpG sites in the first intron of the S100A4gene were ∼90% methylated in microdissected normal pancreatic duct cells using bisulfite-modified sequencing and in two cell lines and three primary pancreatic carcinomas with a reduced or absent expression of S100A4. In contrast, these CpGs were 100% hypomethylated in 11 of 12 pancreatic cancer cell lines by methylation-specific polymerase chain reaction. The association between the expression of S100A4 and hypomethylation of the first intron of S100A4was statistically significant (P= 0.002). These data suggest that the majority of pancreatic carcinomas undergo selection for hypomethylation and overexpression of S100A4. Because most pancreatic carcinomas express S100A4, it may be a useful target for early detection strategies.

Published
2002
Full Text
View/download PDF

199. STK11/LKB1Peutz-Jeghers Gene Inactivation in Intraductal Papillary-Mucinous Neoplasms of the Pancreas

Author

Sato, Norihiro, Rosty, Christophe, Jansen, Marnix, Fukushima, Noriyoshi, Ueki, Takashi, Yeo, Charles J., Cameron, John L., Iacobuzio-Donahue, Christine A., Hruban, Ralph H., and Goggins, Michael

Abstract

Despite the growing awareness of intraductal papillary-mucinous neoplasms (IPMNs) of the pancreas among clinicians, the molecular features of IPMNs have not been well characterized. Previous reports suggest that inactivation of theSTK11/LKB1, a tumor-suppressor gene responsible for Peutz-Jeghers syndrome (PJS), plays a role in the pathogenesis of gastrointestinal hamartomas as well as several cancers, including pancreatic adenocarcinoma. Using polymerase chain reaction amplification of five microsatellite markers from the 19p13.3 region harboring the STK11/LKB1gene, we analyzed DNA from 22 IPMNs for loss of heterozygosity (LOH). LOH at 19p13.3 was identified in 2 of 2 (100%) IPMNs from patients with PJS and 5 of 20 (25%) from patients lacking features of PJS (7 of 22, 32% overall). Sequencing analysis of theSTK11/LKB1gene in these IPMNs with LOH revealed a germline mutation in one IPMN that arose in a patient with PJS and a somatic mutation in 1 of the 20 sporadic IPMNs. None of the 22 IPMNs showed hypermethylation of the STK11/LKB1gene. These results suggest that the STK11/LKB1gene is involved in the pathogenesis of some IPMNs.

Published
2001
Full Text
View/download PDF

200. One-Year Morbidity Following Videoscopic Inguinal Lymphadenectomy for Stage III Melanoma.

Author

Jansen, Marnix R., Vrielink, Otis M., Faut, Marloes, Deckers, Eric A., Been, Lukas B., van Leeuwen, Barbara L., and Chen, Suzie

Subjects
*LYMPHEDEMA, *MELANOMA, *DISEASES, *METASTASIS, *CANCER patients, *SEX distribution, *QUALITY of life, *QUESTIONNAIRES, *DESCRIPTIVE statistics, *RADIOTHERAPY, *SURGICAL excision, *LYMPH node surgery
Abstract

Simple Summary: Inguinal lymphadenectomy (the removal of lymph nodes in the groin) is currently part of the treatment options for stage III melanoma patients. Surgery can be performed using one large inguinal incision (open approach) or a few smaller incisions (videoscopic approach). Previous research has already shown less severe complications and comparable oncologic outcomes after the videoscopic approach. Postoperative lymphedema following inguinal lymphadenectomy is a well-known problem which can potentially decrease quality of life. With the arrival of adjuvant systemic treatment options, less invalidating surgery is highly desirable. However, lymphedema and quality of life have only been investigated after the open approach. Therefore, we evaluated lymphedema and quality of life following videoscopic inguinal lymphadenectomy for stage III melanoma. The videoscopic inguinal lymphadenectomy is a feasible approach due to the comparable lymphedema incidence and normalization of quality of life during follow-up. Purpose: We aimed to elucidate morbidity following videoscopic inguinal lymphadenectomy for stage III melanoma. Methods: Melanoma patients who underwent a videoscopic inguinal lymphadenectomy between November 2015 and May 2019 were included. The measured outcomes were lymphedema and quality of life. Patients were reviewed one day prior to surgery and postoperatively every 3 months for one year. Results: A total number of 34 patients were included for participation; 19 (55.9%) patients underwent a concomitant iliac lymphadenectomy. Lymphedema incidence was 40% at 3 months and 50% at 12 months after surgery. Mean interlimb volume difference increased steadily from 1.8% at baseline to 6.9% at 12 months (p = 0.041). Median Lymph-ICF-LL total score increased from 0.0 at baseline to 12.0 at 3 months, and declined to 8.5 at 12 months (p = 0.007). Twelve months after surgery, Lymph-ICF-LL scores were higher for females (p = 0.021) and patients that received adjuvant radiotherapy (p = 0.013). The Median Distress Thermometer and EORTC QLQ-C30 summary score recovered to baseline at 12 months postoperatively (p = 0.747 and p = 0.203, respectively). Conclusions: The onset of lymphedema is rapid and continues to increase up to one year after videoscopic inguinal lymphadenectomy. Quality of life recovers to the baseline value. [ABSTRACT FROM AUTHOR]

Published
2021
Full Text
View/download PDF

Catalog

Books, media, physical & digital resources
See catalog results