Session 2: Extramural vascular invasion and extranodal deposits: should they be treated the same?

Professor Nagtegaal has already highlighted that lymph nodes are probably not responsible for the development of liver metastases. If they are not, then is there another mechanism? Professor Haboubi addresses the question of extranodal deposits - their frequency and their importance in the development of metastatic disease. The experts review the evidence and discuss whether this information will alter treatment decisions and staging systems in the future.

The degree of extramural spread of T3 rectal cancer: an appeal to the American Joint Committee on Cancer.

The T3 category of the TNM classification includes over 60% of all rectal tumours and encompasses the greatest variance in cancer-specific end-points than any other T category. The most recent edition of the cancer staging handbook of the American Joint Committee on Cancer (AJCC) dated 2010 does not divide T3 tumours into subgroups which reflect cancer-specific outcome more sensitively. The original aim of the present study was to review the literature to assess the influence of the degree of extramural extent of T3 rectal cancer on local recurrence and survival. An article written by the authors was accepted for publication but was withdrawn immediately after they became aware of the publication of the 4th edition of the TNM Supplement by the Union for International Cancer Control dated 2012, which was not accessible by the search system used. This article dealt with the subdivision of the T3 category although this was not included in the most up-to-date AJCC guidelines and was stated to be 'entirely optional'. Medline, PubMed and Cochrane Library searches were performed to identify all studies that investigated the degree of extramural spread and its relationship to survival and local recurrence. Twenty-two studies were identified of which 12 assessed the degree of histopathological extramural spread measured in millimetres. In 18 of the 22 studies the degree of extramural spread was a statistically significant prognostic factor for survival and local recurrence. Analysis of the studies indicated that the subdivision of category T3 rectal cancer into two subgroups of extramural spread ≤ 5 mm or more than 5 mm resulted in markedly different survival and local recurrence rates. The data were insufficient to allow validation of any greater subdivision. Measurement of the extent of extramural spread by MRI before any treatment agreed with the histopathological measurement in the surgical specimen to within 1 mm. The extent of extramural spread in T3 rectal cancer measured in millimetres is a powerful prognostic factor. A subdivision of T3 into T3a and T3b of less than or equal to or more than 5 mm appears to give the greatest discrimination of local recurrence and survival. Preoperative T3 subdivision by MRI has the same sensitivity as histopathological examination of the resected specimen. Given the clinical need for the pretreatment classification of the T3 category for oncological management planning, the evidence strongly indicates that the subdivision of the T3 category by MRI should be formally considered as part of the TNM staging system for rectal cancer.

A collaborative review of the current concepts and challenges of anastomotic leaks in colorectal surgery.

The reduction of the incidence, detection and treatment of anastomotic leakage (AL) continues to challenge the colorectal surgical community. AL is not consistently defined and reported in clinical studies, its occurrence is variably reported and its impact on longterm morbidity and health-care resources has received relatively little attention. Controversy continues regarding the best strategies to reduce the risk. Diagnostic tests lack sensitivity and specificity, resulting in delayed diagnosis and increased morbidity. Intra-operative fluorescence angiography has recently been introduced as a means of real-time assessment of anastomotic perfusion and preliminary evidence suggests that it may reduce the rate of AL. In addition, concepts are emerging about the role of the rectal mucosal microbiome in AL and the possible role of new prophylactic therapies. In January 2016 a meeting of expert colorectal surgeons and pathologists was held in London, UK, to identify the ongoing controversies surrounding AL in colorectal surgery. The outcome of the meeting is presented in the form of research challenges that need to be addressed.

The degree of extramural spread of T3 rectal cancer: a plea to the UICC and AJCC.

The above article, published online on 15 July 2016 in Wiley Online Library (wileyonlinelibrary.com), has been retracted by agreement between the authors, the journal Editor-in-Chief, Neil Mortensen, and John Wiley & Sons Limited. After acceptance the authors were made aware of a contribution to a prior publication of the UICC, TNM Supplement: A commentary on uniform use, 4th Edition, ed. C. Wittekind (Wiley, 2012), p. 195, which renders the central argument of their article invalid. They have therefore asked for it to be withdrawn. A modified version of the paper was published in the January 2017 issue (volume 19; issue 1) with the title "The degree of extramural spread of T3 rectal cancer: an appeal to the American Joint Committee on Cancer".

Histopathological and radiological reporting in rectal cancer: concepts and controversies, facts and fantasies.

In rectal cancer patients, the stage of the disease, local spread and distant metastases status drive the treatment decisions to be made. Histopathology remains the gold standard, but preoperative staging, particularly magnetic resonance imaging (MRI), is pivotal for defining surgical planes and finding patients who could potentially benefit from preoperative regimes. Unfortunately, due to a lack of awareness, expertise and practise the quality of rectal cancer MRI and histopathology reporting varies among centres. This paper highlights the most important and frequently occurring radiological and histopathological discrepancies/mistakes to be aware of.

Interobserver variability amongst gastrointestinal pathologists in assessing prognostic parameters of malignant colorectal polyps: a cause for concern.

BACKGROUND: Malignant colorectal polyps (MCRP) have become a major challenge in the field of coloproctology from diagnosis to full treatment. One important facet of the challenge is the histopathological staging of the lesion and identifying various prognostic parameters. The primary aim of this study was to find the interobserver variation amongst 4 experienced gastrointestinal pathologists when assessing important parameters and staging systems (Haggitt, Kikuchi and Ueno) in MCRPs. METHODS: Four experienced gastrointestinal pathologists independently assessed 56 cases of MCRP, and each pathologist completed a pro forma for each case. The results were collated and statistically analysed. RESULTS: There was a significant variation in the assessments using the various published staging systems agreed upon on important prognostic parameters. CONCLUSIONS: None of the staging systems used is suitable for all polyp types or has good reproducibility. There is an urgent need to make pathologists' assessment of MCRPs easier and more reproducible.

The histopathological mimics of inflammatory bowel disease: a critical appraisal.

The pathological diagnosis of inflammatory bowel disease (IBD) is often difficult because biopsy material may not contain pathognomonic features, making distinction between Crohn's disease, ulcerative colitis and other forms of colitides a truly challenging exercise. The problem is further complicated as several diseases frequently mimic the histological changes seen in IBD. Successful diagnosis is reliant on careful clinicopathological correlation and recognising potential pitfalls. This is best achieved in a multidisciplinary team setting when the full clinical history, endoscopic findings, radiology and relevant serology and microbiology are available. In this review, we present an up-to-date evaluation of the histopathological mimics of IBD.

Pathology and pathogenesis of diverticular disease and patterns of colonic mucosal changes overlying the diverticula.

The aim of this article is to review the pathology of diverticular disease and draw attention to the histological changes that affect the wall and the mucosal lining of the sigmoid colon in this common condition. We were the first group to propose a histological classification for sigmoid colitis-associated diverticular disease, and in this paper we are adding another feature to our original observation.

Histological grading of tumour regression and radiation colitis in locally advanced rectal cancer following neoadjuvant therapy: a critical appraisal.

AIM: Locally advanced rectal cancer is commonly treated by neoadjuvant therapy and the resultant tumour response can be quantified histologically. This therapy may also induce radiation colitis, which also can be graded. The aim of this study was to assess the grading of tumour regression and of radiation colitis and their relationship to other prognostic parameters. METHOD: Between 2000 and 2006, 75 patients (23 women; median duration of follow up, 58 months) with rectal cancer were evaluated. Sixty-three had short-course radiotherapy and 12 had long-course radiotherapy. Tumour regression was graded histologically using the three-point Ryan system: patients with grades 1 and 2 were considered as responders and patients with grade 3 were considered as nonresponders. Radiation colitis was graded histologically as mild, moderate or severe, as described previously (J Pathol 2006; 210: P25). RESULTS: Twenty-nine patients were classified as responders and 46 as nonresponders. The former were less likely to be lymph node positive compared with the latter (P=0.001). Tumour response did not correlate with local recurrence. Responders showed a disease-free survival (not overall survival) advantage at 2 and 5 years over nonresponders. Responders showed a higher rate of postoperative abdominal complications. Histological evidence of regression was demonstrated in patients treated with short-course radiotherapy. There was no relationship between radiation colitis grade and abdominal complications. CONCLUSION: Radiation colitis grade does not correlate with postoperative complications. More abdominal complications occurred in patients receiving long-course radiotherapy.

Magnetic resonance imaging cannot predict histological tumour involvement of a circumferential surgical margin in rectal cancer.

AIM: Several recent studies have attempted to evaluate the accuracy of preoperative magnetic resonance imaging (MRI) in predicting the likelihood of tumour involvement of the postoperative circumferential resection margin (CRM) in rectal cancer with the intention of selecting patients who might benefit from neoadjuvant therapy and as a guide to surgery. The aim of this study was to assess whether such studies can provide a valid answer as to whether preoperative MRI can accurately predict CRM involvement by tumour. METHOD: The study design and methodology of studies on this topic were critically examined. RESULTS: Features identified as affecting the efficacy of these studies were: representativeness of patients, definition of the margin assessed by MRI and by histology, lack of blinding of surgeons and pathologists to MRI results, effect of neoadjuvant treatment, and number of patients studied. CONCLUSION: Because of methodological inadequacies in studies completed to date, there is insufficient evidence of the ability of a positive MRI result to predict an involved CRM. Although MRI may be able to identify a tumour that has extended to the mesorectal fascia and/or intersphincteric plane, logically, it cannot indicate where the surgical boundary of the resection will ultimately lie, and therefore cannot validly predict an involved CRM and should not be relied upon for this purpose.

Radiation bowel disease and its clinical implication.

Pre-operative radiotherapy may induce radiation colitis and tumour regression. Histological evaluation of radiation colitis needs to be reproducible to assess disease progression. The severity of radiation colitis can be assessed and graded according to its histological features. Increased severity of disease appears to be associated with a higher degree of cellular atypia and a lesser eosinophilic infiltrate. The severity of histological changes does not appear to be associated with post-operative complications. Tumour regression is an interesting phenomenon, the histological grading of which is of prognostic importance. Patients treated with long course radiotherapoy appear to have more incidences of postoperative complications. However, these are though to be related to the degree of tumour regression rather than to the type of radiotherapy.

Review of medical and surgical management of Clostridium difficile infection.

Clostridium difficile infection (CDI) has become an important area in our daily clinical practice. C. difficile is known to cause a broad spectrum of conditions ranging from asymptomatic carriage, through mild or moderately severe disease with watery diarrhoea, to the life-threatening pseudomembranous colitis (PMC), with toxic megacolon and ileus. Peoples who have been treated with broad-spectrum antibiotics, patients with serious underlying co-morbidities and the elderly are at greatest risk. Over 80% of CDIs reported are in people aged over 65. Due to the alarming increase in its frequency, appearance of more virulent strains and occasional need for life-saving surgical intervention, a more coherent multidisciplinary approach is needed. Combination of rapid turn round time and accurate diagnosis will result in a better management of CDI and a timely implementation of infection control measure. Discontinuation of causative agents such as antibiotic treatment is often curative. In more serious cases, oral administration of metronidazole or vancomycin is the treatment of choice. Relapses of CDI have been reported in about 20-25% of cases, this may increase to 45-60% after the first recurrence. Patients should be treated as soon as possible when the diagnosis of Clostridium difficile colitis is made to avoid sepsis or bowel perforation. Colectomy may improve the outcome of the patient with systemic or complicated Clostridium difficile colitis. This article reviews the changing epidemiological picture, microbiology, histopathology and both medical and surgical managements.

Lifestyle factors and colorectal cancer risk (2): a systematic review and meta-analysis of associations with leisure-time physical activity.

OBJECTIVE: Increased physical activity may decrease the risk of colorectal cancer. As a prerequisite to the determination of lifestyle attributable risks, we performed a systematic review and meta-analysis of prospective observational studies to quantify gender-specific risk associated with increased leisure-time physical activity (LT-PA). METHOD: We searched MEDLINE and EMBASE (to December 2007), and other sources, selecting reports based on strict inclusion criteria. We used random-effects meta-analyses to estimate summary risk ratios (RR) and 95% confidence intervals (95% CI) for uppermost vs lowermost categories of physical activity. To investigate dose-response, we explored risks ratios as a function of cumulative percentiles of physical activity distribution. RESULTS: Fifteen datasets from 14 articles, including 7873 incident cases, were identified. For colon cancer, there were inverse associations with LT-PA for men (RR: 0.80; 95% CI: 0.67-0.96) and women (0.86; 0.76-0.98). LT-PA did not influence risk of rectal cancer. The dose-response analysis was consistent with linear pattern reductions in risk of colon cancer in both genders. There was evidence of moderate between-study heterogeneity but summary estimates were broadly consistent across potential confounding factors. CONCLUSION: Increased LT-PA is associated with a modest reduction in colon but not rectal cancer risk; a risk reduction, which previously may have been overstated. LT-PA only interventions in public health cancer prevention strategies are unlikely to impact substantially on colorectal cancer incidences.