Novel digital tissue phenotypic signatures of distant metastasis in colorectal cancer
Korsuk Sirinukunwattana, David Snead, David Epstein, Zia Aftab, Imaad Mujeeb, Yee Wah Tsang, Ian Cree, and Nasir Rajpoot
[no publication details given]
Abstract
Distant metastasis is the major cause of death in colorectal cancer (CRC). Patients at high risk of developing distant metastasis could benefit from appropriate adjuvant and follow-up treatments if stratified accurately at an early stage of the disease. Studies have increasingly recognized the role of diverse cellular components within the tumor microenvironment in the development and progression of CRC tumors. In this paper, we show that a new method of automated analysis of digitized images from colorectal cancer tissue slides can provide important estimates of distant metastasis-free survival (DMFS, the time before metastasis is first observed) on the basis of details of the microenvironment. Specifically, we determine what cell types are found in the vicinity of other cell types, and in what numbers, rather than concentrating exclusively on the cancerous cells. We then extract novel tissue phenotypic signatures using statistical measurements about tissue composition. Such signatures can underpin clinical decisions about the advisability of various types of adjuvant therapy.
PDF full text available at https://arxiv.org/pdf/1801.07451.pdf
Showing posts with label colorectal. Show all posts
Showing posts with label colorectal. Show all posts
Monday, 11 December 2017
Glandular Morphometrics for Objective Grading of Colorectal Adenocarcinoma Histology Images
Scientific reports Vol. 7, Iss. 1, (December 4, 2017): 16852.
Determining the grade of colon cancer from tissue slides is a routine part of the pathological analysis. In the case of colorectal adenocarcinoma (CRA), grading is partly determined by morphology and degree of formation of glandular structures. Achieving consistency between pathologists is difficult due to the subjective nature of grading assessment. An objective grading using computer algorithms will be more consistent, and will be able to analyse images in more detail. In this paper, we measure the shape of glands with a novel metric that we call the Best Alignment Metric (BAM). We show a strong correlation between a novel measure of glandular shape and grade of the tumour. We used shape specific parameters to perform a two-class classification of images into normal or cancerous tissue and a three-class classification into normal, low grade cancer, and high grade cancer. The task of detecting gland boundaries, which is a prerequisite of shape-based analysis, was carried out using a deep convolutional neural network designed for segmentation of glandular structures. A support vector machine (SVM) classifier was trained using shape features derived from BAM. Through cross-validation, we achieved an accuracy of 97% for the two-class and 91% for three-class classification.
UHCW Research: Snead, David
Determining the grade of colon cancer from tissue slides is a routine part of the pathological analysis. In the case of colorectal adenocarcinoma (CRA), grading is partly determined by morphology and degree of formation of glandular structures. Achieving consistency between pathologists is difficult due to the subjective nature of grading assessment. An objective grading using computer algorithms will be more consistent, and will be able to analyse images in more detail. In this paper, we measure the shape of glands with a novel metric that we call the Best Alignment Metric (BAM). We show a strong correlation between a novel measure of glandular shape and grade of the tumour. We used shape specific parameters to perform a two-class classification of images into normal or cancerous tissue and a three-class classification into normal, low grade cancer, and high grade cancer. The task of detecting gland boundaries, which is a prerequisite of shape-based analysis, was carried out using a deep convolutional neural network designed for segmentation of glandular structures. A support vector machine (SVM) classifier was trained using shape features derived from BAM. Through cross-validation, we achieved an accuracy of 97% for the two-class and 91% for three-class classification.
UHCW Research: Snead, David
Tuesday, 10 October 2017
NIHR Signal New evidence confirms three-yearly surveillance interval for people at intermediate risk of bowel cancer
From the NIHR Dissemination Centre
People with benign growths (adenomas), who are at intermediate risk of bowel cancer, benefit from follow-up colonoscopy . However, some people at the lower end of risk in this intermediate category may not benefit from this further follow-up. At higher risk, a three-yearly colonoscopy is thought to be sufficient.
This NIHR-funded cohort study reviewed data for 11,944 intermediate-risk patients from UK hospitals and screening trials. Within this group, particular features were identified which placed them at higher risk, such as the presence of larger or highly abnormal adenomas or incomplete colonoscopy. These patients had half the risk of developing cancer if they attended one follow-up colonoscopy three years later, and two-thirds the risk if they attended a second after another three years. For people without these features, the benefits of ongoing surveillance were less clear.
This large-scale study showed that all intermediate-risk patients had increased chance of cancerous growths if the interval since initial screening exceeded three years. This supports the current UK screening schedule.
It may be possible to reduce the frequency of screening in a subgroup of patients at low-intermediate risk. A study of more recent data will be necessary to validate this finding.
People with benign growths (adenomas), who are at intermediate risk of bowel cancer, benefit from follow-up colonoscopy . However, some people at the lower end of risk in this intermediate category may not benefit from this further follow-up. At higher risk, a three-yearly colonoscopy is thought to be sufficient.
This NIHR-funded cohort study reviewed data for 11,944 intermediate-risk patients from UK hospitals and screening trials. Within this group, particular features were identified which placed them at higher risk, such as the presence of larger or highly abnormal adenomas or incomplete colonoscopy. These patients had half the risk of developing cancer if they attended one follow-up colonoscopy three years later, and two-thirds the risk if they attended a second after another three years. For people without these features, the benefits of ongoing surveillance were less clear.
This large-scale study showed that all intermediate-risk patients had increased chance of cancerous growths if the interval since initial screening exceeded three years. This supports the current UK screening schedule.
It may be possible to reduce the frequency of screening in a subgroup of patients at low-intermediate risk. A study of more recent data will be necessary to validate this finding.
Wednesday, 4 October 2017
Caecal cancer presenting as leg erythema and a lung opacity
Necrotising infection of the lower limb is a rare presentation for colorectal malignancy. We report a case of a perforated caecal adenocarcinoma presenting with right leg erythema, pain and swelling in the presence of a right lower lobe lung opacity. Following initial debridement and washout, CT imaging demonstrated a thickened terminal ileum, caecum and appendix, in keeping with primary malignancy. This fed the right-sided lower limb sepsis tracking down from the medial aspect of the psoas muscle to give rise to the multiloculated collection seen in the adductor compartment. The lung lesion measured 16 mm and was metastatic. The patient was successfully managed with a subtotal colectomy and an end ileostomy. The biopsy confirmed an adenocarcinoma (T4N1M1). We highlight the importance of perforated colonic carcinoma as a leading differential for lower limb abscesses. Suspicions should be raised further if accompanied by rounded opacifications on plain film radiography of the lungs.
UHCW Research: Archik Das, Khalid Hureibi, Muhammad Tayyab, Peter McCullough
Tuesday, 26 September 2017
Evidence-based recommendations on cetuximab (Erbitux) and panitumumab (Vectibix) for previously untreated RAS wild-type metastatic colorectal cancer in adults.
This guidance replaces NICE technology appraisal guidance on cetuximab for the first-line treatment of metastatic colorectal cancer (TA176).
This guidance partially updates the terminated NICE technology appraisal on panitumumab in combination with chemotherapy for the treatment of metastatic colorectal cancer (TA240).
In September 2017, this guidance was amended after a change to the commercial arrangements in August 2017. This change does not affect the cost effectiveness of cetuximab. Sections 1.3, 2 and 5.5 have been updated.
This guidance partially updates the terminated NICE technology appraisal on panitumumab in combination with chemotherapy for the treatment of metastatic colorectal cancer (TA240).
In September 2017, this guidance was amended after a change to the commercial arrangements in August 2017. This change does not affect the cost effectiveness of cetuximab. Sections 1.3, 2 and 5.5 have been updated.
Role of tissue microenvironment resident adipocytes in colon cancer
World journal of gastroenterology 23.32: 5829-5835. (August 28, 2017)
Colorectal cancer (CRC) is a multifactorial disease characterized by several genetic and epigenetic alterations occurring in epithelial cells. It is increasingly recognized that tumour progression is also regulated by tumour microenvironment (TME). The bidirectional cross-talk between tumour resident adipocytes and cancer cells within TME has been proposed as active contributor to carcinogenesis. Tumour resident adipocytes exhibit an activated phenotype characterized by increased secretion of pro-tumorigenic factors (angiogenic/inflammatory/immune) which contribute to cancer cell proliferation, invasion, neoangiogenesis, evasion of immune surveillance and therapy resistance. Furthermore, adipocytes represent a fuel rich source for increasing energy demand of rapidly proliferating tumour cells. Interestingly, a relationship between obesity and molecular variants in CRC has recently been identified. Whether adipose tissue promotes cancer progression in subsets of molecular phenotypes or whether local tissue adipocytes are involved in inactivation of tumour suppressor genes and/or activation of oncogenes still needs to be explored. This editorial highlights the major findings related to cross-talk between adipocytes and colon cancer cells and how local paracrine interactions may promote cancer progression. Furthermore, we provide future strategies in studying colonic TME which could provide insights in bidirectional cross-talk mechanisms between adipocytes and colonic epithelial cells. This could enable to decipher critical signalling pathways of both early colonic carcinogenesis and cancer progression.
UHCW Research: Tabuso, Maria and Arasaradnam, Ramesh P.
UHCW Research: Tabuso, Maria and Arasaradnam, Ramesh P.
Tuesday, 19 September 2017
British Society of Gastroenterology position statement on serrated polyps in the colon and rectum
Serrated polyps have been recognised in the last decade
as important premalignant lesions accounting for
between 15% and 30% of colorectal cancers. There is
therefore a clinical need for guidance on how to manage
these lesions; however, the evidence base is limited.
The scope of the position statement was wide-ranging and included: evidence that serrated lesions have premalignant potential; detection and resection of serrated lesions; surveillance strategies after detection of serrated lesions; special situations—serrated polyposis syndrome (including surgery) and serrated lesions in colitis; education, audit and benchmarks and research questions.
Key recommendation: we suggest that until further evidence on the efficacy or otherwise of surveillance are published, patients with sessile serrated lesions (SSLs) that appear associated with a higher risk of future neoplasia or colorectal cancer (SSLs ≥10 mm or serrated lesions harbouring dysplasia including traditional serrated adenomas) should be offered a one-off colonoscopic surveillance examination at 3 years (weak recommendation, low quality evidence, 90% agreement)
The scope of the position statement was wide-ranging and included: evidence that serrated lesions have premalignant potential; detection and resection of serrated lesions; surveillance strategies after detection of serrated lesions; special situations—serrated polyposis syndrome (including surgery) and serrated lesions in colitis; education, audit and benchmarks and research questions.
Key recommendation: we suggest that until further evidence on the efficacy or otherwise of surveillance are published, patients with sessile serrated lesions (SSLs) that appear associated with a higher risk of future neoplasia or colorectal cancer (SSLs ≥10 mm or serrated lesions harbouring dysplasia including traditional serrated adenomas) should be offered a one-off colonoscopic surveillance examination at 3 years (weak recommendation, low quality evidence, 90% agreement)
Tuesday, 5 September 2017
Preoperative chemoradiation with capecitabine, irinotecan and cetuximab in rectal cancer: significance of pre-treatment and post-resection RAS mutations
Br J Cancer. 2017 Aug 31. doi: 10.1038/bjc.2017.294. [Epub ahead of print]
In a prospective phase II trial (EXCITE), patients with magnetic resonance imaging (MRI)-defined non-metastatic rectal adenocarinoma threatening/involving the surgical resection plane received pelvic radiotherapy with concurrent capecitabine, irinotecan and cetuximab. Resection was recommended 8 weeks later. The primary endpoint was histopathologically clear (R0) resection margin. Pre-planned retrospective DNA pyrosequencing (PS) and next generation sequencing (NGS) of KRAS, NRAS, PIK3CA and BRAF was performed on the pre-treatment biopsy and resected specimen.
This regimen was feasible and the primary study endpoint was met. For the first time using pre-operative rectal CRT, emergence of clinically important new resection mutations is described, likely reflecting intratumoural heterogeneity manifesting either as treatment-driven selective clonal expansion or a geographical biopsy sampling miss.
UHCW Research: J. Worlding
In a prospective phase II trial (EXCITE), patients with magnetic resonance imaging (MRI)-defined non-metastatic rectal adenocarinoma threatening/involving the surgical resection plane received pelvic radiotherapy with concurrent capecitabine, irinotecan and cetuximab. Resection was recommended 8 weeks later. The primary endpoint was histopathologically clear (R0) resection margin. Pre-planned retrospective DNA pyrosequencing (PS) and next generation sequencing (NGS) of KRAS, NRAS, PIK3CA and BRAF was performed on the pre-treatment biopsy and resected specimen.
This regimen was feasible and the primary study endpoint was met. For the first time using pre-operative rectal CRT, emergence of clinically important new resection mutations is described, likely reflecting intratumoural heterogeneity manifesting either as treatment-driven selective clonal expansion or a geographical biopsy sampling miss.
UHCW Research: J. Worlding
Thursday, 24 August 2017
Radiofrequency treatment for haemorrhoids [IPG589]
Radiofrequency treatment for haemorrhoids Current evidence on the safety and efficacy of radiofrequency treatment for haemorrhoids is inadequate in quantity and quality. Therefore, this procedure should only be used with special arrangements for clinical governance, consent and audit or research.
Clinicians wishing to do radiofrequency treatment for haemorrhoids should: Inform the clinical governance leads in their NHS trusts.
Ensure that patients understand the uncertainty about the procedure's safety and efficacy and provide them with clear written information. In addition, the use of NICE's information for the public is recommended.
Audit and review clinical outcomes of all patients having radiofrequency treatment for haemorrhoids (see section 7.1).
Clinicians wishing to do radiofrequency treatment for haemorrhoids should: Inform the clinical governance leads in their NHS trusts.
Ensure that patients understand the uncertainty about the procedure's safety and efficacy and provide them with clear written information. In addition, the use of NICE's information for the public is recommended.
Audit and review clinical outcomes of all patients having radiofrequency treatment for haemorrhoids (see section 7.1).
Thursday, 10 August 2017
Atezolizumab (Tecentriq) and Cobimetinib (Cotellic) for advanced/metastatic colorectal cancer - third line
The combination of atezolizumab (Tecentriq), given by injection, and cobimetinib (Cotellic), given orally, is being developed to increase the options available for the treatment of mCRC. This treatment combination will target people that have received at least two previous treatments and did not show any improvements or who initially benefitted but whose disease has since progressed. It is thought that this treatment combination will increase the survival rates for people with mCRC.
From the NIHR Innovation Observatory
Quantitative faecal immunochemical tests to guide referral for colorectal cancer in primary care - guidance (DG30)
New diagnostics guidance from NICE on quantitative faecal immunochemical tests (OC Sensor, HM-JACKarc and FOB Gold) to guide GP referral for colorectal cancer.
The OC Sensor, HM‑JACKarc and FOB Gold quantitative faecal immunochemical tests are recommended for adoption in primary care to guide referral for suspected colorectal cancer in people without rectal bleeding who have unexplained symptoms but do not meet the criteria for a suspected cancer pathway referral outlined in NICE's guideline on suspected cancer (recommendations 1.3.1 to 1.3.3).
Results should be reported using a threshold of 10 micrograms of haemoglobin per gram of faeces. Companies should provide advice about the performance characteristics of the assays to laboratories, and ensure standardisation of results
The OC Sensor, HM‑JACKarc and FOB Gold quantitative faecal immunochemical tests are recommended for adoption in primary care to guide referral for suspected colorectal cancer in people without rectal bleeding who have unexplained symptoms but do not meet the criteria for a suspected cancer pathway referral outlined in NICE's guideline on suspected cancer (recommendations 1.3.1 to 1.3.3).
Results should be reported using a threshold of 10 micrograms of haemoglobin per gram of faeces. Companies should provide advice about the performance characteristics of the assays to laboratories, and ensure standardisation of results
Thursday, 20 July 2017
Understanding of a negative bowel screening result and potential impact on future symptom appraisal and help-seeking behaviour: a focus group study
Health Expectations. Volume 20, Issue 4. August 2017. Pages 584–592
Colorectal cancer (CRC) screening using a faecal occult blood test (FOBt) has the potential to reduce cancer-related mortality. Symptom vigilance remains crucial as a proportion of cancers will be diagnosed between screening rounds. A negative FOBt has the potential to influence how participants respond to future symptoms of CRC.
Participants recognized that reassurance from a negative FOBt could lead to a short-term delay in help-seeking if symptoms developed. Screening programmes should seek to emphasize the importance of the temporal nature of FOBt results with key messages about symptom recognition and prompt help-seeking behaviour
UHCW Research: Steve Smith
Colorectal cancer (CRC) screening using a faecal occult blood test (FOBt) has the potential to reduce cancer-related mortality. Symptom vigilance remains crucial as a proportion of cancers will be diagnosed between screening rounds. A negative FOBt has the potential to influence how participants respond to future symptoms of CRC.
Participants recognized that reassurance from a negative FOBt could lead to a short-term delay in help-seeking if symptoms developed. Screening programmes should seek to emphasize the importance of the temporal nature of FOBt results with key messages about symptom recognition and prompt help-seeking behaviour
UHCW Research: Steve Smith
Monday, 10 July 2017
Locality Sensitive Deep Learning for Detection and Classification of Nuclei in Routine Colon Cancer Histology Images
IEEE Transactions on Medical Imaging ( Volume: 35, Issue: 5, May 2016 )
Detection and classification of cell nuclei in histopathology images of cancerous tissue stained with the standard hematoxylin and eosin stain is a challenging task due to cellular heterogeneity. Deep learning approaches have been shown to produce encouraging results on histopathology images in various studies. In this paper, we propose a Spatially Constrained Convolutional Neural Network (SC-CNN) to perform nucleus detection. SC-CNN regresses the likelihood of a pixel being the center of a nucleus, where high probability values are spatially constrained to locate in the vicinity of the centers of nuclei. For classification of nuclei, we propose a novel Neighboring Ensemble Predictor (NEP) coupled with CNN to more accurately predict the class label of detected cell nuclei. The proposed approaches for detection and classification do not require segmentation of nuclei. We have evaluated them on a large dataset of colorectal adenocarcinoma images, consisting of more than 20,000 annotated nuclei belonging to four different classes. Our results show that the joint detection and classification of the proposed SC-CNN and NEP produces the highest average F1 score as compared to other recently published approaches. Prospectively, the proposed methods could offer benefit to pathology practice in terms of quantitative analysis of tissue constituents in whole-slide images, and potentially lead to a better understanding of cancer.
UHCW Research:
Detection and classification of cell nuclei in histopathology images of cancerous tissue stained with the standard hematoxylin and eosin stain is a challenging task due to cellular heterogeneity. Deep learning approaches have been shown to produce encouraging results on histopathology images in various studies. In this paper, we propose a Spatially Constrained Convolutional Neural Network (SC-CNN) to perform nucleus detection. SC-CNN regresses the likelihood of a pixel being the center of a nucleus, where high probability values are spatially constrained to locate in the vicinity of the centers of nuclei. For classification of nuclei, we propose a novel Neighboring Ensemble Predictor (NEP) coupled with CNN to more accurately predict the class label of detected cell nuclei. The proposed approaches for detection and classification do not require segmentation of nuclei. We have evaluated them on a large dataset of colorectal adenocarcinoma images, consisting of more than 20,000 annotated nuclei belonging to four different classes. Our results show that the joint detection and classification of the proposed SC-CNN and NEP produces the highest average F1 score as compared to other recently published approaches. Prospectively, the proposed methods could offer benefit to pathology practice in terms of quantitative analysis of tissue constituents in whole-slide images, and potentially lead to a better understanding of cancer.
UHCW Research:
Monday, 26 June 2017
OC-057 Undetectable faecal immunochemical test for haemoglobin excludes colorectal cancer in symptomatic patients: a prospective uk study
The diagnosis of colorectal cancer (CRC) in primary care can be challenging as symptoms are variable with poor specificity. We investigated the diagnostic accuracies of faecal immunochemical test for haemoglobin (FIT) and faecal calprotectin (FCP) in symptomatic patients referred from primary care for urgent lower gastrointestinal investigations via the two-week wait colorectal pathway.
UHCW Research: M. M. Widlak, C. L. T|homas, C. Tomkins, C. Darby, N. O'Connell, S. Wurie, L. Burns, C. Harmston, R. P. Aradaradnan, C. Evans and C. U. Nwokolo
UHCW Research: M. M. Widlak, C. L. T|homas, C. Tomkins, C. Darby, N. O'Connell, S. Wurie, L. Burns, C. Harmston, R. P. Aradaradnan, C. Evans and C. U. Nwokolo
Wednesday, 31 May 2017
Endoscopic full thickness removal of non-lifting colonic polyps
Interventional Procedures Guidance from NICE on endoscopic full thickness removal of non-lifting colonic polyps. This involves using a special device to remove the polyp and seal the bowel wall closed afterwards.
Friday, 26 May 2017
Royal College of Surgeons & Bowel Cancer UK to invest half a million pounds in bowel cancer surgical research
Bowel Cancer UK, in partnership with the Royal College of Surgeons of
England, announce £500,000 funding for bowel cancer surgical research to
establish the UK’s first Colorectal Cancer Surgical Research Chair and
establish a network of Bowel Cancer UK Colorectal Cancer Surgical
Research Fellows.
Monday, 24 April 2017
Differences in managing a 'significant polyp' which may harbour a cancer detected at bowel screening or in symptomatic patients: The significant polyp and early colorectal cancer (SPECC) program initial findings
Thursday, 30 March 2017
Cetuximab and panitumumab for previously untreated metastatic colorectal cancer
New NICE Technology Appraisal Guidance on cetuximab (Erbitux) and panitumumab (Vectibix) for previously untreated RAS wild-type metastatic colorectal cancer in adults.
Wednesday, 8 March 2017
Suction drainage after rectal cancer surgery does not reduce infection
Placing a suction drain in the pelvic cavity does not reduce the risk of pelvic infection after commonly-used surgery for rectal cancer. A French trial comparing results of surgery with and without pelvic drainage showed no difference in risk of infection within 30 days. The risk of infection was about 17%. The drainage technique is less commonly used in the UK.
From the NIHR Dissemination Centre
From the NIHR Dissemination Centre
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