Review
Oncology
Lauriane Onfroy-Roy, Dimitri Hamel, Laurent Malaquin, Audrey Ferrand
Summary: Colorectal cancer (CRC) is the third most common cause of cancer-related death. Patients with inflammatory bowel disease have an increased risk of CRC. The interactions between fibroblasts and ISCs in the colon may play a crucial role in the initiation of CRC due to chronic inflammation. Despite improvements in CRC treatment, including better detection and drug strategies, CRC remains a public health concern.
Article
Cell Biology
Helen J. S. Jones, Chris Cunningham, Hanne A. Askautrud, Havard E. Danielsen, David J. Kerr, Enric Domingo, Tim Maughan, Simon J. Leedham, Viktor H. Koelzer
Summary: After local excision of early rectal cancer, accurate assessment of recurrence risk is crucial. Current measures are suboptimal, so this study assessed three measures of tumor stromal content in a cohort of rectal cancer patients without prior radiotherapy. The ratio of desmoplastic to inflamed stroma determined by a deep neural network was found to be the most powerful predictor of disease recurrence.
Article
Engineering, Biomedical
Xiaobei Luo, Eliza Li Shan Fong, Chaojun Zhu, Quy Xiao Xuan Lin, Man Xiong, Aimin Li, Tingting Li, Touati Benoukraf, Hanry Yu, Side Liu
Summary: This study developed a comprehensive three-dimensional model by establishing in vitro conditions for co-culturing colorectal cancer PDO and patient-derived CAFs, which helps to maintain the characteristics of tumor cells. Ultimately, this model is suitable for evaluating standard-of-care drugs and potentially useful for personalized cancer medicine.
ACTA BIOMATERIALIA
(2021)
Review
Biochemistry & Molecular Biology
Natalie Geyer, Marco Gerling
Summary: The Hedgehog (Hh) signaling pathway plays a diverse role in colorectal cancer, with the canonical pathway acting as a tumor suppressor while non-canonical activation may promote tumor growth in certain cells. Researchers suggest that a more detailed understanding of the Hh signaling pathway could lead to the development of new cancer therapies in the future, despite discouraging results from previous clinical trials.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Oncology
Chun-Chi Lin, Te-Hung Chen, Yu-Chung Wu, Chuan-Yin Fang, Jaw-Yuan Wang, Chou-Pin Chen, Kai-Wen Huang, Jeng-Kai Jiang
Summary: Taiwan has seen a rise in colorectal cancer cases, with 40-60% of them metastasizing. Continuous updating of cytoreductive strategies in metastatic CRC has improved overall survival to 40 months. A group of experts from TSCRS in Taiwan established evidence-based recommendations for defining resectability criteria in mCRC through consultations and discussions. The final consensus includes eight recommendations regarding metastasis resection criteria, local control treatment in liver resectable patients, synchronous liver metastases management, peritoneal metastasis approach, resection in multiple-organ metastasis, and general resectability criteria. Patients undergoing R0 resection have the greatest survival advantage, and MDTs play a key role in providing rapid and safe treatment. The TSCRS consensus statement aims to enhance clinical capacity within MDTs and optimize healthcare resources.
ANNALS OF SURGICAL ONCOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Adam R. Markowski, Agnieszka U. Blachnio-Zabielska, Karolina Pogodzinska, Anna J. Markowska, Piotr Zabielski
Summary: Colorectal cancer is a heterogeneous group of tumors with varied clinical and pathological features based on anatomical location. Sphingolipids play a role in cancer formation and progression, and their changes are important in carcinogenesis. This study analyzed the sphingolipid profile in colorectal cancer and found differences in cellular sphingolipid amounts between rectal and colonic cancer. The study also revealed qualitative and quantitative disturbances in sphingolipid metabolism in colorectal cancer, indicating the complexity of changes during cancer development depending on the tumor's location.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Review
Oncology
Jinlai Gao, Zhangguo Shen, Zaixing Deng, Lina Mei
Summary: Tumor-stroma ratio (TSR) is a promising prognostic indicator for colorectal cancer (CRC) patients, with low TSR associated with worse prognosis in terms of disease-free survival (DFS) and overall survival (OS). The study found significantly higher hazard ratios for patients with low TSR in stage II CRC, stage III CRC, and mixed stage CRC, suggesting a predictive relevance for poor outcomes in these patients.
FRONTIERS IN ONCOLOGY
(2021)
Article
Medicine, General & Internal
Dan Jiang, Tarjei S. Hveem, Mark Glaire, David N. Church, David J. Kerr, Li Yang, Havard E. Danielsen
Summary: This study demonstrates the prognostic value of combined T-lymphocyte and stroma fractions in early colorectal cancer. Low stroma fraction and high stroma fraction can identify low-risk and high-risk subgroups, respectively, providing valuable guidance for patient treatment strategies.
Article
Oncology
Satoru Furuhashi, Matias A. Bustos, Shodai Mizuno, Suyeon Ryu, Yalda Naeini, Anton J. Bilchik, Dave S. B. Hoon
Summary: The incidence of sporadic early-onset colon cancer (EOCC) has increased worldwide, but the molecular mechanisms in the tumor and tumor microenvironment (TME) are not fully understood. This study reveals the unique transcriptomic and proteomic profiles in tumor epithelial cells and cancer-associated fibroblasts (CAFs) in EOCC, and identifies the association between FAP(+) CAFs with upregulated WNT signaling and higher FGF20 levels at the tumor invasive margin.
NPJ PRECISION ONCOLOGY
(2023)
Article
Oncology
Kai M. Brown, Aiqun Xue, Ross C. Smith, Jaswinder S. Samra, Anthony J. Gill, Thomas J. Hugh
Summary: This study validated the prognostic significance of stromal protein biomarkers in primary CRC and CRLM, and identified key differences in stromal gene expression between paired primary CRC and CRLM, as well as several targetable biomarkers and transcriptomic pathways.
Article
Chemistry, Multidisciplinary
Chenglei Li, Zhaohuan Li, Xue Gong, Jianhao Liu, Tingyue Zheng, Fangqing Wang, Jingliang Wu, Bo Zhang
Summary: Cancer-associated fibroblasts (CAFs) are crucial in tumor invasion and metastasis within the tumor microenvironment (TME). A novel TME acid-responsive liposome co-delivering IRI and 398 was developed, showing decreased CAF activation, increased cytotoxicity, enhanced drug accumulation, superior anti-tumor activity in mice, and anti-metastatic efficiency. This combinational approach offers promising prospects for cancer therapy.
Article
Oncology
Sanne ten Hoorn, Cynthia Waasdorp, Martijn G. H. van Oijen, Helene Damhofer, Anne Trinh, Lan Zhao, Lisanne J. H. Smits, Sanne Bootsma, Gabi W. van Pelt, Wilma E. Mesker, Linda Mol, Kaitlyn K. H. Goey, Miriam Koopman, Jan Paul Medema, Jurriaan B. Tuynman, Inti Zlobec, Cornelis J. A. Punt, Louis Vermeulen, Maarten F. Bijlsma
Summary: This study identifies ADAM12 as a serum marker for stromal activation in colorectal cancer, especially in the case of primary cancers located in the rectum. ADAM12 levels were found to be prognostic, particularly in metastatic rectal cancer and mesenchymal subtype tumors. Additionally, ADAM12 showed potential for predicting recurrence in non-metastatic rectal cancer.
Article
Oncology
Li-Chun Chang, Chia-Tung Shun, Been-Ren Lin, Silvia Sanduleanu, Weng-Feng Hsu, Ming-Shiang Wu, Han-Mo Chiu
Summary: A study conducted at the National Taiwan University Hospital from 2005 to 2014 compared the disease-free survival of T1 cancer arising from the rectum versus the colon. The results showed that T1 rectal cancer had a higher risk of recurrence compared to T1 colon cancer, with rectal location being an independent risk factor for recurrence. Further research is needed to explore whether adjuvant therapy or closer surveillance can reduce the risk of recurrence in T1 rectal cancer.
Article
Biochemistry & Molecular Biology
Kathleen M. McAndrews, Karina Vazquez-Arreguin, Changsoo Kwak, Hikaru Sugimoto, Xiaofeng Zheng, Bingrui Li, Michelle L. Kirtley, Valerie S. LeBleu, Raghu Kalluri
Summary: The study demonstrates that alpha SMA(+) CAFs in CRC exert tumor-restraining functions via BMP4/TGF beta 1 paracrine signaling that serves to suppress Lgr5(+) CSCs and promote anti-tumor immunity, ultimately limiting CRC progression.
Article
Pathology
Silvia Miller, Svenja Bauer, Matthias Schrempf, Gerhard Schenkirsch, Andreas Probst, Bruno Markl, Benedikt Martin
Summary: Based on the investigation of 253 cases of pT3 and pT4 colorectal adenocarcinomas, the study confirmed that a low tumor proportion is associated with an adverse prognosis, while the previous assumption that a high tumor proportion might also be a risk factor for metastasis was not confirmed. Furthermore, the study showed that the semiautomatic technique used was not superior to the established method, suggesting the need for continued improvement in prognostic techniques.
PATHOLOGY RESEARCH AND PRACTICE
(2021)
Article
Pathology
Susan D. Richman, Gemma Hemmings, Helen Roberts, Niall Gallop, Rachel Dodds, Lyndsay Wilkinson, Jonathan Davis, Rhian White, Emma Yates, Bharat Jasani, Louise Brown, Tim S. Maughan, Rachel Butler, Philip Quirke, Richard Adams
Summary: FOCUS4 trial is a successful umbrella trial for patients with advanced colorectal cancer, using molecular profiling for biomarker analysis.
JOURNAL OF CLINICAL PATHOLOGY
(2023)
Article
Respiratory System
Rebecca J. Birch, Daniel Peckham, Henry M. Wood, Philip Quirke, Rob Konstant-Hambling, Keith Brownlee, Rebecca Cosgriff, Nicholas Burr, Amy Downing
Summary: It has been found that individuals with Cystic Fibrosis (CF) have a higher risk of developing colorectal cancer (CRC), and carriers of cystic fibrosis transmembrane conductance regulator (CFTR) mutations may also face an increased risk. With the increasing life expectancy of CF patients, more individuals are at risk of developing CRC.
JOURNAL OF CYSTIC FIBROSIS
(2023)
Article
Oncology
Dion Morton, Matthew Seymour, Laura Magill, Kelly Handley, James Glasbey, Bengt Glimelius, Andy Palmer, Jenny Seligmann, Soren Laurberg, Keigo Murakami, Nick West, Philip Quirke, Richard Gray, FOxTROT Collaborative Grp
Summary: Neoadjuvant chemotherapy shows potential benefits for locally advanced colon cancer compared to postoperative chemotherapy. In this study, patients with radiologically staged T3-4, N0-2, M0 colon cancer were randomly assigned to receive 6 weeks of preoperative oxaliplatin-fluoropyrimidine chemotherapy followed by either 18 or 24 weeks postoperatively. Results indicate that neoadjuvant chemotherapy results in marked downstaging of tumors and lower rates of incomplete resections and disease recurrence within 2 years.
JOURNAL OF CLINICAL ONCOLOGY
(2023)
Review
Gastroenterology & Hepatology
Hideki Ueno, Iris D. Nagtegaal, Philip Quirke, Kenichi Sugihara, Yoichi Ajioka
Summary: Tumor deposits (TDs), discontinuous tumor spread, negatively impact survival in approximately 20% of colorectal cancer patients. Revisions on TD definition and categorization in the TNM system have been partially successful, but alternative staging methods, such as the counting method, have shown superior prognostic and diagnostic value. An international discussion on optimal TD treatment is needed to ensure patients receive the best possible adjuvant treatment.
ANNALS OF GASTROENTEROLOGICAL SURGERY
(2023)
Article
Microbiology
Mayilvahanan Bose, Henry Wood, Caroline Young, Philip Quirke, Ramakrishan Ayloor Seshadri
Summary: It has been found that changes in the gut microbiome can be either a cause or a correlation of colorectal cancer. Most of this research has been conducted in developed countries with high incidence of CRC, and it is unknown if lower incidence countries like India have similar microbial associations. This study collected and sequenced microbial samples from 46 Indian CRC patients and 43 healthy volunteers, demonstrating similarities to other Asian samples and a global CRC microbiome, but also highlighting regional variation and the importance of developing protocols and infrastructure for microbiome research in different countries.
Article
Cell Biology
Jan Moritz Niehues, Philip Quirke, Nicholas P. West, Heike I. Grabsch, Marko van Treeck, Yoni Schirris, Gregory P. Veldhuizen, Gordon G. A. Hutchins, Susan D. Richman, Sebastian Foersch, Titus J. Brinker, Junya Fukuoka, Andrey Bychkov, Wataru Uegami, Daniel Truhn, Hermann Brenner, Alexander Brobeil, Michael Hoffmeister, Jakob Nikolas Kather
Summary: Deep learning can predict microsatellite instability (MSI) from routine histopathology slides of colorectal cancer (CRC). It is unclear whether DL can also predict other biomarkers with high performance and whether DL predictions generalize to external patient populations.
CELL REPORTS MEDICINE
(2023)
Article
Oncology
Sophia J. Wagner, Daniel Reisenbuechler, Nicholas P. West, Jan Moritz Niehues, Jiefu Zhu, Sebastian Foersch, Gregory Patrick Veldhuizen, Philip Quirke, Heike I. Grabsch, Piet A. van den Brandt, Gordon G. A. Hutchins, Susan D. Richman, Tanwei Yuan, Rupert Langer, Josien C. A. Jenniskens, Kelly Offermans, Wolfram Mueller, Richard Gray, Stephen B. Gruber, Joel K. Greenson, Gad Rennert, Joseph D. Bonner, Daniel Schmolze, Jitendra Jonnagaddala, Nicholas J. Hawkins, Robyn L. Ward, Dion Morton, Matthew Seymour, Laura Magill, Marta Nowak, Jennifer Hay, Viktor H. Koelzer, David N. Church, Christian Matek, Carol Geppert, Chaolong Peng, Cheng Zhi, Xiaoming Ouyang, Jacqueline A. James, Maurice B. Loughrey, Manuel Salto-Tellez, Hermann Brenner, Michael Hoffmeister, Daniel Truhn, Julia A. Schnabel, Melanie Boxberg, Tingying Peng, Jakob Nikolas Kather
Summary: This study develops a new transformer-based pipeline for predicting prognostic biomarkers from colorectal cancer pathology slides. The results show that this approach significantly improves performance, generalizability, data efficiency, and interpretability compared to current algorithms. The method also solves a longstanding diagnostic problem by achieving clinical-grade performance on endoscopic biopsy tissue.
Letter
Oncology
Richard Gray, Matt Seymour, Laura Magill, Kelly Handley, Philip Quirke, Nick West, Dion Morton
JOURNAL OF CLINICAL ONCOLOGY
(2023)
Article
Surgery
Morten F. S. Hartwig, Mustafa Bulut, Jens Ravn-Eriksen, Lasse B. Hansen, Rasmus D. Bojesen, Mads Falk Klein, Henrik L. Jakobsen, Morten Rasmussen, Bo Rud, Jens-Ole Eriksen, Susanne Eiholm, Anne-Marie K. Fiehn, Phil Quirke, Ismail Gogenur
Summary: The study aimed to assess the feasibility of Combined Endoscopic and Laparoscopic Surgery (CELS) in high-risk patients with early colon cancer. The results showed that CELS resection was feasible in selected patients and could spare some patients from undergoing large bowel resection.
SURGICAL ENDOSCOPY AND OTHER INTERVENTIONAL TECHNIQUES
(2023)
Article
Critical Care Medicine
Ahmed Abdul Hadi Harb Nasser, Rohan Prakash, Charles Handford, Khabab Osman, Govind Singh Chauhan, Rajpal Nandra, Ansar Mahmood, Varun Dewan, Jerome Davidson, Mohammed Al-Azzawi, Christian Smith, Mothana Gawad, Ioannis Palaiologos, Rory Cuthbert, Warran Wignadasan, Daniel Banks, James Archer, Abdulrahman Odeh, Thomas Moores, Muaaz Tahir, Margaret Brooks, Gurdeep Biring, Stevan Jordan, Zain Elahi, Mohammed Shaath, Manoj Veettil, Chiranjit De, Charles Handford, Mohit Bansal, Akshdeep Bawa, Ahmed Mattar, Varun Tandra, Audrina Daadipour, Ahmed Taha, Shafat Gangoo, Sriram Srinivasan, Mandishona Tarisai, Basil Budair, Krishna Subbaraman, Farrukh Khan, Austin Gomindes, Arjun Samuel, Niel Kang, Karan Kapur, Elizabeth Mainwaring, Hannah Bridgwater, Andre Lo, Usman Ahmed, Tahir Khaleeq, Ahmed El-Bakoury, Ramy Rashed, Hazem Hosny, Rathan Yarlagadda, Jonathan Keenan, Ahmed Hamed, Bryan Riemer, Arham Qureshi, Vatsal Gupta, Matthew Waites, Sabri Bleibleh, David Westacott, Jonathan Phillips, Jamie East, Daniel Huntley, Saqib Masud, Yusuf Mirza, Sandeep Mishra, David Dunlop, Mohamed Khalefa, Balakumar Balasubramanian, Mahesh Thibbaiah, Olivia Payton, James Berstock, Krisna Deano, Khaled Sarraf, Kartik Logishetty, George Lee, Hariharan Subbiah-Ponniah, Nirav Shah, Aakaash Venkatesan, James Cheseldene-Culley, Joseph Ayathamattam, Samantha Tross, Sukhwinder Randhawa, Faisal Mohammed, Ramla Ali, Jonathan Bird, Kursheed Khan, Muhammad Adeel Akhtar, Andrew Brunt, Panagiotis Roupakiotis, Padmanabhan Subramanian, Nelson Bua, Mounir Hakimi, Samer Bitar, Majed Al Najjar, Ajay Radhakrishnan, Charlie Gamble, Andrew James, Catherine Gilmore, Dan Dawson, Rajesh Sofat, Mohamed Antar, Aashish Raghu, Sam Heaton, Waleed Tawfeek, Christerlyn Charles, Henry Burnand, Sean Duffy, Luke Taylor, Laura Magill, Rita Perry, Michala Pettitt, Kelvin Okoth, Thomas Pinkney
Summary: This study aimed to explore the factors influencing the in-hospital mortality of periprosthetic fractures (PPFs) involving the hip joint. The results showed that age, sex, mental test score, pneumonia, renal failure, history of peripheral vascular disease, and deep surgical site infection were independently associated with mortality. Treatment method was not a significant predictor of mortality. The in-hospital mortality rate of PPFs around the hip exceeded 5%.
INJURY-INTERNATIONAL JOURNAL OF THE CARE OF THE INJURED
(2023)
Article
Oncology
Li Yang, Jinlin Yang, Andreas Kleppe, Havard E. Danielsen, David J. Kerr
Summary: The current standard-of-care adjuvant treatment for patients with colorectal cancer is chemotherapy selected on the basis of conventional histopathological staging criteria; however, the clinical benefit from these regimens is limited. The authors of this Perspective discuss strategies to minimize toxicity and monitor efficacy of these regimens, and propose new tools for disease staging that could enable more personalized treatment decisions.
NATURE REVIEWS CLINICAL ONCOLOGY
(2023)
