Publications by authors named "Paul J Finan"

24 Publications

  • Page 1 of 1

Impact of the COVID-19 pandemic on the detection and management of colorectal cancer in England: a population-based study.

Lancet Gastroenterol Hepatol 2021 03 15;6(3):199-208. Epub 2021 Jan 15.

Clinical Trial Service Unit and Epidemiological Studies Unit, Nuffield Department of Population Health, University of Oxford, Oxford, UK; Medical Research Council Population Health Research Unit, Nuffield Department of Population Health, University of Oxford, Oxford, UK; Big Data Institute, University of Oxford, Oxford, UK.

Background: There are concerns that the COVID-19 pandemic has had a negative effect on cancer care but there is little direct evidence to quantify any effect. This study aims to investigate the impact of the COVID-19 pandemic on the detection and management of colorectal cancer in England.

Methods: Data were extracted from four population-based datasets spanning NHS England (the National Cancer Cancer Waiting Time Monitoring, Monthly Diagnostic, Secondary Uses Service Admitted Patient Care and the National Radiotherapy datasets) for all referrals, colonoscopies, surgical procedures, and courses of rectal radiotherapy from Jan 1, 2019, to Oct 31, 2020, related to colorectal cancer in England. Differences in patterns of care were investigated between 2019 and 2020. Percentage reductions in monthly numbers and proportions were calculated.

Findings: As compared to the monthly average in 2019, in April, 2020, there was a 63% (95% CI 53-71) reduction (from 36 274 to 13 440) in the monthly number of 2-week referrals for suspected cancer and a 92% (95% CI 89-95) reduction in the number of colonoscopies (from 46 441 to 3484). Numbers had just recovered by October, 2020. This resulted in a 22% (95% CI 8-34) relative reduction in the number of cases referred for treatment (from a monthly average of 2781 in 2019 to 2158 referrals in April, 2020). By October, 2020, the monthly rate had returned to 2019 levels but did not exceed it, suggesting that, from April to October, 2020, over 3500 fewer people had been diagnosed and treated for colorectal cancer in England than would have been expected. There was also a 31% (95% CI 19-42) relative reduction in the numbers receiving surgery in April, 2020, and a lower proportion of laparoscopic and a greater proportion of stoma-forming procedures, relative to the monthly average in 2019. By October, 2020, laparoscopic surgery and stoma rates were similar to 2019 levels. For rectal cancer, there was a 44% (95% CI 17-76) relative increase in the use of neoadjuvant radiotherapy in April, 2020, relative to the monthly average in 2019, due to greater use of short-course regimens. Although in June, 2020, there was a drop in the use of short-course regimens, rates remained above 2019 levels until October, 2020.

Interpretation: The COVID-19 pandemic has led to a sustained reduction in the number of people referred, diagnosed, and treated for colorectal cancer. By October, 2020, achievement of care pathway targets had returned to 2019 levels, albeit with smaller volumes of patients and with modifications to usual practice. As pressure grows in the NHS due to the second wave of COVID-19, urgent action is needed to address the growing burden of undetected and untreated colorectal cancer in England.

Funding: Cancer Research UK, the Medical Research Council, Public Health England, Health Data Research UK, NHS Digital, and the National Institute for Health Research Oxford Biomedical Research Centre.
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March 2021

National variation in pulmonary metastasectomy for colorectal cancer.

Colorectal Dis 2020 Dec 25. Epub 2020 Dec 25.

Nuffield Department of Population Health, Big Data Institute, University of Oxford, Oxford, UK.

Aim: Evidence on patterns of use of pulmonary metastasectomy in colorectal cancer patients is limited. This population-based study aims to investigate the use of pulmonary metastasectomy in the colorectal cancer population across the English National Health Service (NHS) and quantify the extent of any variations in practice and outcome.

Methods: All adults who underwent a major resection for colorectal cancer in an NHS hospital between 2005 and 2013 were identified in the COloRECTal cancer data Repository (CORECT-R). All inpatient episodes corresponding to pulmonary metastasectomy, occurring within 3 years of the initial colorectal resection, were identified. Multi-level logistic regression was used to determine patient and organizational factors associated with the use of pulmonary metastasectomy for colorectal cancer, and Kaplan-Meier and Cox models were used to assess survival following pulmonary metastasectomy.

Results: In all, 173 354 individuals had a major colorectal resection over the study period, with 3434 (2.0%) undergoing pulmonary resection within 3 years. The frequency of pulmonary metastasectomy increased from 1.2% of patients undergoing major colorectal resection in 2005 to 2.3% in 2013. Significant variation was observed across hospital providers in the risk-adjusted rates of pulmonary metastasectomy (0.0%-6.8% of patients). Overall 5-year survival following pulmonary resection was 50.8%, with 30-day and 90-day mortality of 0.6% and 1.2% respectively.

Conclusions: This study shows significant variation in the rates of pulmonary metastasectomy for colorectal cancer across the English NHS.
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December 2020

Improving outcome prediction in individuals with colorectal cancer and diabetes by accurate assessment of vascular complications: Implications for clinical practice.

Eur J Surg Oncol 2020 Nov 3. Epub 2020 Nov 3.

Nuffield Department of Population Health, Big Data Institute, Old Road Campus, University of Oxford, Headington, Oxford, OX3 7LF, UK.

Background: Diabetes is considered a risk factor for mortality following a diagnosis of cancer. We hypothesised that the risk will vary due to the heterogeneous nature of the population and accurate classification of vascular complications will improve prediction of clinical outcomes.

Methods: The COloRECTal cancer data Repository (CORECT-R) was used to identify individuals with primary colorectal cancer, who underwent surgical resection in England (2005-2016). Diabetes was recorded using ICD10 codes (E10-E14) during inpatient hospital admission in the six years preceding cancer diagnosis, complication status was determined using the adapted Diabetes Complications Severity Index (aDCSI). Survival and post-operative outcomes were compared between groups.

Results: Of 232,367 individuals, 28,642 (12.3%) were recorded as having diabetes, 49.2% of whom had complications according to the aDCSI. Patients with diabetes complications had increased incidence of adverse post-operative outcomes (90-day post-operative mortality (6.6% versus 3.2%) and death during the surgical episode (7.9% versus 3.6%)), compared to those without diabetes. Those without complications had rates comparable to the population without diabetes. The odds of death within a year of diagnosis were higher for those with complicated diabetes compared to those without diabetes [OR 1.58 (95%CI 1.51-1.66) p < 0.01], but no difference was observed between those with uncomplicated diabetes and those without diabetes [OR 1.05 (95%CI 0.99-1.11) p = 0.10].

Conclusions: Prediction of outcome following surgery in colorectal cancer patients with diabetes relies on the accurate assessment of complications. This study suggests that the poor post-operative outcomes in diabetes patients may be associated with diabetes complication rather than diabetes itself.
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November 2020

Thirty years of the Association of Coloproctology of Great Britain and Ireland.

Colorectal Dis 2020 Oct 13. Epub 2020 Oct 13.

Association of Coloproctology of Great Britain and Ireland, Lincolns Inn Fields, London, UK.

This is a summary of the history of the Association of Coloproctology of Great Britain and Ireland from its inception in the late 1980s to the present day.
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October 2020

Variation in post-colonoscopy colorectal cancer across colonoscopy providers in English National Health Service: population based cohort study.

BMJ 2019 11 13;367:l6090. Epub 2019 Nov 13.

Cancer Epidemiology Group, Institute of Cancer and Pathology and Institute of Data Analytics, University of Leeds, Leeds LS2 9JT, UK.

Objectives: To quantify post-colonoscopy colorectal cancer (PCCRC) rates in England by using recent World Endoscopy Organisation guidelines, compare incidence among colonoscopy providers, and explore associated factors that could benefit from quality improvement initiatives.

Design: Population based cohort study.

Setting: National Health Service in England between 2005 and 2013.

Population: All people undergoing colonoscopy and subsequently diagnosed as having colorectal cancer up to three years after their investigation (PCCRC-3yr).

Main Outcome Measures: National trends in incidence of PCCRC (within 6-36 months of colonoscopy), univariable and multivariable analyses to explore factors associated with occurrence, and funnel plots to measure variation among providers.

Results: The overall unadjusted PCCRC-3yr rate was 7.4% (9317/126 152), which decreased from 9.0% in 2005 to 6.5% in 2013 (P<0.01). Rates were lower for colonoscopies performed under the NHS bowel cancer screening programme (593/16 640, 3.6%), while they were higher for those conducted by non-NHS providers (187/2009, 9.3%). Rates were higher in women, in older age groups, and in people with inflammatory bowel disease or diverticular disease, in those with higher comorbidity scores, and in people with previous cancers. Substantial variation in rates among colonoscopy providers remained after adjustment for case mix.

Conclusions: Wide variation exists in PCCRC-3yr rates across NHS colonoscopy providers in England. The lowest incidence was seen in colonoscopies performed under the NHS bowel cancer screening programme. Quality improvement initiatives are needed to address this variation in rates and prevent colorectal cancer by enabling earlier diagnosis, removing premalignant polyps, and therefore improving outcomes.
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November 2019

Variation in the Use of Resection for Colorectal Cancer Liver Metastases.

Ann Surg 2019 11;270(5):892-898

Cancer Epidemiology Group, Leeds Institute for Data Analytics, University of Leeds, Leeds, UK.

Objective: The aim of this study was to investigate variation in the frequency of resections for colorectal cancer liver metastases across the English NHS.

Background: Previous research has shown significant variation in access to liver resection surgery across the English NHS. This study uses more recent data to identify whether inequalities in access to liver resection still persist.

Methods: All adults who underwent a major resection for colorectal cancer in an NHS hospital between 2005 and 2012 were identified in the COloRECTal cancer data Repository (CORECT-R). All episodes of care, occurring within 3 years of the initial bowel operation, corresponding to liver resection were identified.

Result: During the study period 157,383 patients were identified as undergoing major resection for a colorectal tumor, of whom 7423 (4.7%) underwent ≥1 liver resections. The resection rate increased from 4.1% in 2005, reaching a plateau around 5% by 2012. There was significant variation in the rate of liver resection across hospitals (2.1%-12.2%). Patients with synchronous metastases who have their primary colorectal resection in a hospital with an onsite specialist hepatobiliary team were more likely to receive a liver resection (odds ratio 1.22; 95% confidence interval, 1.10-1.35) than those treated in one without. This effect was absent in resection for metachronous metastases.

Conclusions: This study presents the largest reported population-based analysis of liver resection rates in colorectal cancer patients. Significant variation has been observed in patient and hospital characteristics and the likelihood of patients receiving a liver resection, with the data showing that proximity to a liver resection service is as important a factor as deprivation.
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November 2019

Understanding the impact of socioeconomic differences in colorectal cancer survival: potential gain in life-years.

Br J Cancer 2019 05 1;120(11):1052-1058. Epub 2019 May 1.

Biostatistics Research Group, Department of Health Sciences, University of Leicester, University Road, LE1 7RH, Leicester, UK.

Background: Colorectal cancer prognosis varies substantially with socioeconomic status. We investigated differences in life expectancy between socioeconomic groups and estimated the potential gain in life-years if cancer-related survival differences could be eliminated.

Methods: This population-based study included 470,000 individuals diagnosed with colon and rectal cancers between 1998 and 2013 in England. Using flexible parametric survival models, we obtained a range of life expectancy measures by deprivation status. The number of life-years that could be gained if differences in cancer-related survival between the least and most deprived groups were removed was also estimated.

Results: We observed up to 10% points differences in 5-year relative survival between the least and most deprived. If these differences had been eliminated for colon and rectal cancers diagnosed in 2013 then almost 8231 and 7295 life-years would have been gained respectively. This results for instance in more than 1-year gain for each colon cancer male patient in the most deprived group on average. Cancer-related differences are more profound earlier on, as conditioning on 1-year survival the main reason for socioeconomic differences were factors other than cancer.

Conclusion: This study highlights the importance of policies to eliminate socioeconomic differences in cancer survival as in this way many life-years could be gained.
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May 2019

Rectal cancer in old age -is it appropriately managed? Evidence from population-based analysis of routine data across the English national health service.

Eur J Surg Oncol 2019 Jul 7;45(7):1196-1204. Epub 2019 Jan 7.

Cancer Epidemiology Group, Leeds Institute for Data Analytics, Worsley Building, University of Leeds, LS2 9NL, UK.

Background: There is significant debate as to where to draw the line between undertreating older rectal cancer patients and minimising treatment risks. This study sought to examine the use of radical rectal cancer treatments and associated outcomes in relation to age across the English NHS.

Methods: Patient, tumour and treatment characteristics for all patients diagnosed with a first primary rectal cancer in England between 1st April 2009 and 31st December 2014 were obtained from the CORECT-R data repository. Descriptive analyses and adjusted logistic regression models were undertaken to examine any association between age and the use of major resection and post-surgical outcomes. Funnel plots were used to show variation in adjusted rates of major resection.

Results: The proportion of patients who underwent a major surgical resection fell from 66.5% to 31.7%, amongst those aged <70 and aged ≥80 respectively. After adjustment, 30-day post-operative mortality, failure to rescue and prolonged length of stay were significantly higher among the oldest group when compared to the youngest. Patient reported outcomes were not significantly worse amongst older patients. Significant variation was observed in adjusted surgical resection rates in the oldest patients between NHS Trusts. The probability of death due to cancer was comparable across all age groups.

Conclusions: Older patients who are selected for surgery have good outcomes, often comparable to their younger counterparts. Significant variation in the treatment of older patients could not be explained by differences in measured characteristics and required further investigation.
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July 2019

Functional Outcomes and Health-Related Quality of Life After Curative Treatment for Rectal Cancer: A Population-Level Study in England.

Int J Radiat Oncol Biol Phys 2019 04 13;103(5):1132-1142. Epub 2018 Dec 13.

Leeds Institute of Medical Research at St James's, University of Leeds, Leeds, UK.

Purpose: There is a growing population of cancer survivors at risk of treatment-related morbidity. This study investigated how potentially curative rectal cancer treatment influences subsequent function and health-related quality of life using data from a large-scale survey of patient-reported outcomes.

Methods And Materials: All individuals 12 to 36 months after receiving a diagnosis of colorectal cancer in England were sent a survey in January 2013. The survey responses were linked with cancer registration, hospital admissions, and radiation therapy data through the National Cancer Registration and Analysis Service. Outcome measures were cancer specific (Functional Assessment of Cancer Therapy and Social Difficulties Inventory items related to fecal incontinence, urinary incontinence, and sexual difficulties) and generic (EuroQol EQ-5D).

Results: Surveys were returned by 6713 (64.2%) of 10,452 patients with rectal cancer. Of these, 3998 patients were in remission after a major resection and formed the final analysis sample. Compared with those who had surgery alone, patients who received preoperative radiation therapy had higher odds of reporting poor bowel control (43.6% vs 33.0%; odds ratio [OR] = 1.55; 95% confidence interval [CI], 1.26-1.91), severe urinary leakage (7.2% vs 3.5%; OR = 1.69; 95% CI, 1.18-2.43), and severe sexual difficulties (34.4% vs 18.3%; OR = 1.73; 95% CI, 1.43-2.11). Patients who received long-course chemoradiotherapy reported significantly better bowel control than those who had short-course radiation therapy, with no difference for other outcomes. Respondents with a stoma present reported significantly higher levels of severe sexual difficulties and worse health-related quality of life than those who had never had a stoma or had undergone stoma reversal.

Conclusions: This study demonstrated the feasibility of a large-scale assessment of patient-reported outcomes and provided "real-world" data regarding the effect of rectal cancer treatment. The results show that patients who receive preoperative radiation therapy reported poorer outcomes, particularly for bowel and sexual function, and highlighted the negative impact of a stoma. We hope that our experience will encourage researchers to perform similar studies in other healthcare systems.
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April 2019

A retrospective observational study of length of stay in hospital after colorectal cancer surgery in England (1998-2010).

Medicine (Baltimore) 2016 Nov;95(47):e5064

Cancer Epidemiology Group, Section of Epidemiology and Biostatistics, Leeds Institute of Cancer & Pathology, University of Leeds Knowledge and Intelligence Team (Northern & Yorkshire) National Cancer Registration Service (Northern & Yorkshire), Public Health England Leeds Institute of Cancer & Pathology, University of Leeds, St James's University Hospital, Leeds, UK.

The National Health Service (NHS) is facing financial constraints and thus there is considerable interest in ensuring the shortest but optimal hospital stays possible. The aim of this study was to investigate patterns of postoperative length of stay (LOS) stay across the English NHS and to identify factors that significantly influence both optimal and prolonged LOS.Data were obtained from the National Cancer Data Repository (NCDR). National patterns of LOS were examined and multilevel mixed effects logistic regression was used to study factors associated with an "ideal" (≤5 days) or a prolonged (≥21 days) LOS in hospital after major resection. Funnel plots were used to examine variation across hospitals in both risk-adjusted and unadjusted LOS.All 240,873 individuals who underwent major resection for colorectal cancer were diagnosed between 1998 and 2010 in the English NHS. The overall median LOS was 10 (interquartile range [IQR] 7-14 days) days, but it fell over time from 11 (IQR 9-15) days in 1998 to 7 (IQR 5-12) days in 2010. The proportion of people experiencing "ideal" LOS increased dramatically from 4.9% in 1998 to 34.2% in 2010, but the decrease in the proportion of patients who experienced a prolonged LOS was less marked falling from 11.2% to 8.4%, respectively. Control charts showed that there was significant variation in short and prolonged LOS across NHS trusts even after adjustment for case-mix.Significant variation in LOS existed between NHS hospitals in England throughout period 1998 to 2010. Understanding the underlying causes of this variation between surgical providers will make it possible to identify and spread best practice, improve services, and ultimately reduce LOS following colorectal cancer surgery.
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November 2016

High hospital research participation and improved colorectal cancer survival outcomes: a population-based study.

Gut 2017 01 19;66(1):89-96. Epub 2016 Oct 19.

Leeds Institute of Cancer and Pathology, University of Leeds, St James's University Hospital, Leeds, UK.

Objective: In 2001, the National Institute for Health Research Cancer Research Network (NCRN) was established, leading to a rapid increase in clinical research activity across the English NHS. Using colorectal cancer (CRC) as an example, we test the hypothesis that high, sustained hospital-level participation in interventional clinical trials improves outcomes for all patients with CRC managed in those research-intensive hospitals.

Design: Data for patients diagnosed with CRC in England in 2001-2008 (n=209 968) were linked with data on accrual to NCRN CRC studies (n=30 998). Hospital Trusts were categorised by the proportion of patients accrued to interventional studies annually. Multivariable models investigated the relationship between 30-day postoperative mortality and 5-year survival and the level and duration of study participation.

Results: Most of the Trusts achieving high participation were district general hospitals and the effects were not limited to cancer 'centres of excellence', although such centres do make substantial contributions. Patients treated in Trusts with high research participation (≥16%) in their year of diagnosis had lower postoperative mortality (p<0.001) and improved survival (p<0.001) after adjustment for casemix and hospital-level variables. The effects increased with sustained research participation, with a reduction in postoperative mortality of 1.5% (6.5%-5%, p<2.2×10) and an improvement in survival (p<10; 5-year difference: 3.8% (41.0%-44.8%)) comparing high participation for ≥4 years with 0 years.

Conclusions: There is a strong independent association between survival and participation in interventional clinical studies for all patients with CRC treated in the hospital study participants. Improvement precedes and increases with the level and years of sustained participation.
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January 2017

Post-colonoscopy colorectal cancer (PCCRC) rates vary considerably depending on the method used to calculate them: a retrospective observational population-based study of PCCRC in the English National Health Service.

Gut 2015 Aug 21;64(8):1248-56. Epub 2014 Nov 21.

Gloucestershire Hospitals NHS Foundation Trust, Gloucester, UK.

Objective: Post-colonoscopy colorectal cancer (PCCRC) is a key quality indicator of colonoscopy. This study compares methods for defining PCCRC rates, proposes a new method of calculating them and quantifies them across the English National Health Service (NHS).

Design: This retrospective observational population-based study involved all individuals with a first primary diagnosis of colorectal cancer made between 2001 and 2010 and treated in the English NHS. Previously published methods for deriving PCCRC rates were applied to the linked routine health data for this population to investigate the effect on the rate. A new method, based on the year of the colonoscopy rather than colorectal cancer diagnosis, was then used to calculate PCCRC rates.

Results: Of 297,956 individuals diagnosed with colorectal cancer, a total of 94,648 underwent a colonoscopy in the 3 years prior to their diagnosis. The application of the published methods and exclusion criteria to the dataset produced significantly different PCCRC rates from 2.5% to 7.7%. The new method demonstrates that PCCRC rates within 3 years of colonoscopy (without exclusions) decreased in the English NHS over 8 years, falling from 10.6% to 7.3% for colonoscopies performed in 2001 and 2007 respectively.

Conclusions: The method used to determine PCCRC rates significantly affects findings with potential to substantially underestimate rates. To enable international benchmarking there needs to be a standardised method for defining PCCRC. This study proposes a new methodology using colonoscopy as a denominator and between 2001 and 2007 this method indicated an 8.6% PCCRC rate across the English NHS. It also demonstrated PCCRC rates have fallen over time.
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August 2015

Thirty-day postoperative mortality after colorectal cancer surgery in England.

Gut 2011 Jun 12;60(6):806-13. Epub 2011 Apr 12.

Colorectal Cancer Epidemiology Group, Centre for Epidemiology and Biostatistics, University of Leeds, St James's Institute of Oncology, St James's Hospital Leeds, Leeds, UK.

Objectives: To assess the variation in risk-adjusted 30-day postoperative mortality for patients with colorectal cancer between hospital trusts within the English NHS.

Design: Retrospective cross-sectional population-based study of data extracted from the National Cancer Data Repository.

Setting: All providers of major colorectal cancer surgery within the English NHS.

Participants: All 160,920 individuals who underwent major resection for colorectal cancer diagnosed between 1998 and 2006 in the English NHS. Main outcome measures National patterns of 30-day postoperative mortality were examined and logistic binary regression was used to study factors associated with death within 30 days of surgery. Funnel plots were used to show variation between trusts in risk-adjusted mortality.

Results: Overall 30-day mortality was 6.7% but decreased over time from 6.8% in 1998 to 5.8% in 2006. The largest reduction in mortality was seen in 2005 and 2006. Postoperative mortality increased with age (15.0% (95% CI 14.1% to 15.9%) for those aged >80 years), comorbidity (24.2% (95% CI 22.0% to 26.5%) for those with a Charlson comorbidity score ≥ 3), stage of disease (9.9% (95% CI 9.3% to 10.6%) for patients with Dukes' D disease), socioeconomic deprivation (7.8% (95% CI 7.2% to 8.4%) for residents of the most deprived quintile) and operative urgency (14.9% (95% CI 14.2% to 15.7%) for patients undergoing emergency resection). Risk-adjusted control charts showed that one trust had consistently significantly better outcomes and three had significantly worse outcomes than the population mean.

Conclusions: Significant variation in 30-day postoperative mortality following major colorectal cancer surgery existed between NHS hospitals in England throughout the period 1998-2006. Understanding the underlying causes of this variation between surgical providers will make it possible to identify and spread best practice, improve outcomes and, ultimately, reduce 30-day postoperative mortality following colorectal cancer surgery.
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June 2011

Lymphatic vessel distribution in the mucosa and submucosa and potential implications for T1 colorectal tumors.

Dis Colon Rectum 2011 Jan;54(1):35-40

The Leeds Institute of Molecular Medicine, University of Leeds, Leeds, UK.

Purpose: Colorectal cancer spreads to lymph nodes via surrounding lymphatic vasculature. Once this spread has occurred, the prognosis of the patient is significantly worse. Lymphatics are difficult to identify on hematoxylin and eosin stains and lack of specific markers has meant that little is known about their distribution in colorectal tissue. The national bowel cancer screening program has resulted in an increase in the diagnosis of T1 colorectal cancers. Patients with suitable T1 tumors can avoid bowel resections and their associated morbidity with the advances in local resection techniques. This means, however, that formal staging and lymph node assessment cannot be performed. Prognostic tools are required to predict risk of lymph node metastases. Studies assessing risk of lymph node spread in T1 tumors have found that invasion of the tumor into the deepest third of the submusosa affords a much greater risk. We hypothesized that this might be due to the quantity or characteristics of lymphatic vasculature in this third.

Methods: A specific lymphatic marker, D2-40 was applied to 5-μm sections of normal colorectal tissue from 45 patients. Slides were scanned and analyzed using Aperio's ImageScope software for PC. Analysis boxes of fixed area were placed within the mucosal layer and within each third of the submucosal layer allowing characteristics of the lymphatics in each third to be quantified individually.

Results: Lymphatic vessels were found in the mucosal layer of all samples although these were significantly smaller than the submucosal vessels (P = .0005). Lymphatics were significantly more numerous in the superficial third of the submucosa (P = .0005); however, vessel size was similar in Sm1, Sm2, and Sm3.

Conclusion: The deepest third of the submucosa contains the smallest number of lymphatic vessels despite invasion into this layer being associated with a higher risk of lymph node spread.
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January 2011

Complete mesocolic excision with central vascular ligation produces an oncologically superior specimen compared with standard surgery for carcinoma of the colon.

J Clin Oncol 2010 Jan 30;28(2):272-8. Epub 2009 Nov 30.

Pathology & Tumour Biology, Leeds Institute of Molecular Medicine, Level 4, Wellcome Trust Brenner Building, St James's University Hospital, Beckett St, Leeds, LS9 7TF, United Kingdom.

Purpose: The plane of surgery in colonic cancer has been linked to patient outcome although the optimal extent of mesenteric resection is still unclear. Surgeons in Erlangen, Germany, routinely perform complete mesocolic excision (CME) with central vascular ligation (CVL) and report 5-year survivals of higher than 89%. We aimed to further investigate the importance of CME and CVL surgery for colonic cancer by comparison with a series of standard specimens.

Methods: The fresh photographs of 49 CME and CVL specimens from Erlangen and 40 standard specimens from Leeds, United Kingdom, for primary colonic adenocarcinoma were collected. Precise tissue morphometry and grading of the plane of surgery were performed before comparison to histopathologic variables.

Results: CME and CVL surgery removed more tissue compared with standard surgery in terms of the distance between the tumor and the high vascular tie (median, 131 v 90 mm; P < .0001), the length of large bowel (median, 314 v 206 mm; P < .0001), and ileum removed (median, 83 v 63 mm; P = .003), and the area of mesentery (19,657 v 11,829 mm(2); P < .0001). In addition, CME and CVL surgery was associated with more mesocolic plane resections (92% v 40%; P < .0001) and a greater lymph node yield (median, 30 v 18; P < .0001).

Conclusion: Surgeons in Erlangen routinely practicing CME and CVL surgery remove more mesocolon and are more likely to resect in the mesocolic plane when compared with standard excisions. This, along with the associated greater lymph node yield, may partially explain the high 5-year survival rates reported in Erlangen.
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January 2010

Morphology of the mesorectum in patients with primary rectal cancer.

Dis Colon Rectum 2009 Jun;52(6):1122-9

Department of Colorectal Surgery, Leicester Royal Infirmary, Leicester, United Kingdom.

Purpose: The size and contents of the pelvis differ between the genders, and this may affect mesorectal size and shape. The aim of this prospective pilot study was to examine radiologically the applied anatomy of the mesorectum.

Methods: Fifty-eight patients (35 male, 23 female) with primary rectal cancer who had suitable high-resolution staging pelvic magnetic resonance images between November 2002 and July 2004 were studied. Ten variables of mesorectal morphology were measured on axial images at the ischial spines. The associations between morphologic variables and gender and body mass index were examined.

Results: Compared with female patients, male patients had a larger area of overall mesorectal package (3,776 mm2 vs. 2,772 mm2, P = 0.001), larger area of mesorectal fat (2,562 mm2 vs. 1,842 mm2, P = 0.001), and higher ratio of anteroposterior to transverse diameter of the mesorectal package (0.82 vs. 0.56, P < 0.001). The anterior mesorectal fat buffer was significantly thinner in females than in males (2.9 mm vs. 7.8 mm, P < 0.001). Mesorectal fat area was greater in males with a body mass index >25 than with a body mass index <25.

Conclusions: Males have a larger overall mesorectal package compared with females, mainly caused by mesorectal fat. The anterior mesorectal fat is significantly thinner in females than in males. Such morphologic differences may affect resection margin status.
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June 2009

Controversial topics in surgery: Splenic flexure mobilisation for anterior resection performed for sigmoid and rectal cancer.

Ann R Coll Surg Engl 2008 Nov;90(8):638-42

St Mark's Hospital, Harrow, Middlesex, UK.

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November 2008

Pathology grading of colon cancer surgical resection and its association with survival: a retrospective observational study.

Lancet Oncol 2008 Sep 28;9(9):857-65. Epub 2008 Jul 28.

Pathology and Tumour Biology, Leeds Institute of Molecular Medicine, University of Leeds, Leeds, UK.

Background: High-quality rectal cancer surgery is known to improve patient outcome. We aimed to assess the quality of colon cancer surgery by studying the extent of variation in the plane of surgical resection, the amount of tissue removed, and its association with survival.

Methods: All resections for primary colon adenocarcinoma done at Leeds General Infirmary (Leeds, UK) between Jan 1, 1997, and June 30, 2002, were identified. The specimens were photographed and graded according to the plane of mesocolic dissection. Tissue morphometry was done on 253 tumours. Univariate and multivariate models were used to ascertain whether there was an association with 5-year survival. The primary outcome measure was overall survival defined as death from any cause.

Findings: 521 cancers were identified, 122 were excluded because of either no photographic images or insufficient images to allow retrospective grading, leaving 399 specimens for analysis. There was marked variation in the proportion of each plane of surgery: muscularis propria in 95 of 399 (24%) specimens, intramesocolic in 177 of 399 (44%) specimens, and mesocolic in 127 of 399 (32%) specimens. Mean cross-sectional tissue area outside the muscularis propria was significantly higher with mesocolic plane surgery (mean 2181 [SD 895] mm(2)) compared with intramesocolic (mean 2109 [1273] mm(2)) and muscularis propria plane (mean 1447 [913] mm(2)) surgery (p=0.0003). There was also a significant increase in the distance from the muscularis propria to the mesocolic resection margin with mesocolic plane surgery (mean 44 [21] mm) compared with intramesocolic (mean 30 [16] mm) and muscularis propria plane (mean 21 [12] mm) surgery, which was independent of tumour site (all excisions p<0.0001). We noted a 15% (95% CI) overall survival advantage at 5 years with mesocolic plane surgery compared with surgery in the muscularis propria plane (HR 0.57 [0.38-0.85], p=0.006) in univariate analysis. However, this association was no longer significant in the multivariate model (HR 0.86 [95% CI 0.56-1.31], p=0.472), but was especially noted in patients with stage III cancers (HR 0.45 [95% CI 0.24-0.85], p=0.014; multivariate analysis). The plane of surgery and amount of mesocolon removed varied between the different sites with better planes in left-sided resections than right-sided ones, which were better than transverse resection (p<0.0001).

Interpretation: As previously shown in the rectum, we have now shown there is marked variability in the plane of surgery achieved in colon cancer. Improving the plane of dissection might improve survival, especially in patients with stage III disease. If confirmed by clinical trial data, such as from the ongoing National Cancer Research Institute Fluoropyrimidine, Oxaliplatin and Targeted Receptor pre-Operative Therapy for colon cancer (FOxTROT) trial of neoadjuvant chemotherapy in advanced resectable colon cancer, improvement of the plane of dissection might be a new cost-effective method of decreasing morbidity and mortality in patients with colon cancer.
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September 2008

Evidence of the oncologic superiority of cylindrical abdominoperineal excision for low rectal cancer.

J Clin Oncol 2008 Jul 9;26(21):3517-22. Epub 2008 Jun 9.

Pathology and Tumour Biology, Leeds Institute of Molecular Medicine, University of Leeds, United Kingdom.

Purpose: Abdominoperineal excision (APE) of the rectum and anus for rectal cancer continues to have greater local recurrence and poorer survival than that seen following anterior resection. Changing to an extended prone perineal dissection results in a more cylindrical specimen and should improve outcomes.

Patients And Methods: One hundred twenty-eight specimens from patients who underwent APE that was performed for potentially curable primary rectal adenocarcinoma were dissected according to standard protocol in Leeds and Stockholm between 1997 and 2007 and were studied. Tissue morphometry was performed on the cross sectional photographs of 93 patient cases.

Results: The cylindrical technique removed more tissue in the distal rectum and in all slices that contained tumor compared with the standard operation (both P < .0001). Greater distance was observed from the muscularis propria or internal sphincter to the anterior, posterior, and lateral resection margins (all P < .0001). This was associated with lower circumferential resection margin (CRM) involvement (14.8% v 40.6%; P = .013) and intraoperative perforations (3.7% v 22.8%; P = .0255). An increase in the amount of tissue removed in the distal rectum (P < .0001) was demonstrated by a single surgeon who changed from the standard to the cylindrical technique during the study period; the change was associated with a reduction in CRM positivity (from 36.2% to 12.5%) and in perforations (from 12.8% to 0.0%).

Conclusion: Cylindrical APE performed in the prone position for low rectal cancer removes more tissue around the tumor that leads to a reduction in CRM involvement and intraoperative perforations, which should reduce local disease recurrence. The cylindrical technique has the potential to improve patient outcomes substantially if appropriate surgical education programs are developed.
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July 2008

Contribution of posture to anorectal manometric measurements: are the measurements in left-lateral position physiologic?

Dis Colon Rectum 2007 Dec;50(12):2112-9

Department of Colorectal Surgery, The General Infirmary at Leeds, Leeds, West Yorkshire, United Kingdom.

Purpose: Anorectal manometry is commonly used to investigate fecal incontinence. Traditional practice dictates that measurements are performed with the patient in the left-lateral position however, episodes of fecal incontinence usually occur in the erect position. The influence of erect posture on anorectal manometry has not been studied.

Methods: We examined the contribution of posture to commonly measured variables during manometry by performing assessment in the left-lateral position and the erect posture. Maximum mean resting pressure, vector volumes, and resting pressure gradient were compared.

Results: Complete data were available for 172 patients. Median age was 55 (interquartile range, 44-65) years. Thirty-seven (22 percent) patients were continent, and 135 (78 percent) were incontinent. Both resting pressure and vector volume increased significantly in the erect position for both continent (P = 0.008 and 0.001, respectively) and incontinent (P = 0.001 for both) patients. A significant negative correlation was seen between severity of incontinence and resting pressure in the erect posture and amount of change in maximum mean resting pressure from left-lateral to erect posture (Spearman coefficients = -0.203, -0.211, and P = 0.013, 0.017, respectively) but not with maximum mean resting pressure in the left-lateral position (Spearman coefficient = -0.119; P = 0.164).

Conclusions: Our study shows significant increase in measurements of manometric variables in the erect position. The increase may be related to anal cushions, which have a significant role in this position. The measurements in erect posture are better correlated with severity of incontinence and may be a more physiologic method of performing anorectal manometry.
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December 2007

Evaluation of a protocol-based management of rectal cancer.

Dis Colon Rectum 2006 Nov;49(11):1703-9

Department of Colorectal Surgery, The General Infirmary at Leeds, Leeds, West Yorkshire, United Kingdom.

Introduction: The management of rectal cancer is multidisciplinary. We have devised and implemented a standardized protocol. This study was designed to evaluate the protocol and identify areas for improvement.

Methods: All patients with a diagnosis of rectal cancer were staged preoperatively. Magnetic resonance imaging and computed tomography were used to predict whether surgical resection would be complete (RO) or involved (R1/2). Data were collected on preoperative adjuvant therapy, surgical procedure, and subsequent pathologic stage, including circumferential resection margin status.

Results: Between January 2000 and October 2002, 163 patients were studied (107 male; median age, 70 (range, 60-77) years). One hundred and fifty seven patients underwent surgical excision for rectal cancer of whom 155 were discussed in the multidisciplinary meeting. One hundred seventeen patients (75 percent) had pelvic magnetic resonance scan and staging computed tomography of chest and abdomen, whereas 38 had computed tomography only. Seventy-seven tumors were predicted as R0 and 78 as likely R1/2. In the predicted RO group, 50 had surgery alone, 25 had short-course radiotherapy, and 2 had chemoradiotherapy. Twelve patients (15.5 percent) had involved circumferential resection margin on the histologic specimen. In the predicted R1/2 group (n = 78), 40 patients received chemoradiotherapy, 11 had short-course radiotherapy, and 27 had surgery alone. Thirty patients (38.4 percent) had involved circumferential resection margin. Circumferential margin involvement was seen in 11 of 40 patients (27.5 percent) who received chemoradiotherapy, 6 of 11 patients (54.5 percent) who received short-course preoperative radiotherapy, and 13 of 27 patients (48.1 percent) who had surgery alone.

Conclusions: Protocol-driven management of rectal cancer within the context of a multidisciplinary team has been demonstrated to work. Regular audit allows for modification and improvement of the protocol as newer management strategies evolve.
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November 2006

A randomized, double-blind trial of the effect of metronidazole on pain after closed hemorrhoidectomy.

Dis Colon Rectum 2002 Sep;45(9):1186-90; discussion 1190-1

Department of Surgery and Centre for Digestive Diseases, The General Infirmary at Leeds, United Kingdom.

Purpose: Patients consider hemorrhoidectomy to be a painful operation. Attempts to reduce the length of inpatient stay have concentrated mainly on a reduction in postoperative pain. Metronidazole has been shown to reduce pain after open hemorrhoidectomy. The aim of this study was to evaluate the effect of metronidazole after closed hemorrhoidectomy.

Methods: Thirty-eight patients undergoing closed hemorrhoidectomy were randomly allocated to receive metronidazole 400 mg (n = 18) or placebo (n = 20) three times daily for seven postoperative days. All patients received a stool softener and analgesics perioperatively. Linear analog scales were used to assess expected pain, actual pain and patient satisfaction. Time to first bowel movement, return to normal activity, complications, and use of additional analgesics were recorded.

Results: Both groups of patients experienced less pain than expected. Patients in the metronidazole group required fewer additional analgesics postoperatively (6.3 vs. 26.3 percent), and satisfaction scores in the placebo group were higher at one week (0.5 vs. 2.5), although these differences were not statistically significant. There were no differences in pain actually experienced, time to first bowel movement, return to normal activity, or complications between the two groups. Satisfaction scores at six weeks for all patients were relatively high, with no significant difference between the groups.

Conclusion: Closed hemorrhoidectomy results in high patient satisfaction and low pain scores. The use of postoperative metronidazole did not reduce postoperative pain.
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September 2002

Role of resting pressure gradient in the investigation of idiopathic fecal incontinence.

Dis Colon Rectum 2002 May;45(5):668-73

Department of Surgery, Centre for Digestive Diseases at Leeds General Infirmary, Leeds, West Yorkshire, United Kingdom.

Purpose: One-third of patients who suffer from idiopathic fecal incontinence are found to have maximum mean resting pressures within the normal range. The objective of this study was to determine whether measuring the gradient of pressure at rest throughout the anal canal is a more sensitive predictor of incontinence in these patients.

Methods: Anorectal physiology measurements were retrospectively reviewed in patients referred over an 18-month period. Two patient groups were selected for the study: Group 1, continent patients (n = 80); and Group 2, patients with idiopathic fecal incontinence (n = 47). Maximum resting pressures, vector volumes, and resting pressure gradients were all contrasted, sensitivities and specificities were calculated, and receiver operating characteristic curve analyses were performed. Reproducibility studies were also performed for the calculation of the pressure gradient.

Results: Patient demographics were similar in the two groups. The resting pressure gradient, maximum mean resting pressure, and vector volumes were significantly lower in incontinent patients compared with the normal patients (P < 0.0001, all comparisons). The sensitivity (and specificity) of resting pressure gradient, maximum mean resting pressure, and vector volumes were 89 percent (96 percent), 55 percent (98 percent), and 53 percent (88 percent), respectively.

Conclusion: The resting pressure gradient is the most accurate in detecting fecal incontinence. The authors conclude that this test is simple, reproducible, and identifies an abnormality in the majority of patients with idiopathic fecal incontinence.
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May 2002

Rates of circumferential resection margin involvement vary between surgeons and predict outcomes in rectal cancer surgery.

Ann Surg 2002 Apr;235(4):449-57

Department of Histopathology, Leeds Teaching Hospitals NHS Trust, Leeds, United Kingdom.

Objective: To analyze the potential variability in rates of circumferential resection margin (CRM) involvement between different surgeons and time periods and to determine the suitability of using CRM status as an immediate predictor of outcome after rectal cancer surgery.

Summary Background Data: After disease stage has been taken into account, survival in rectal cancer has been shown to be very variable between surgeons and institutions. One of the major factors influencing survival is local recurrence, and this in turn is strongly related to inadequate tumor excision, particularly at the CRM.

Methods: In a study involving 608 patients who underwent surgery for rectal cancer in Leeds during the 12-year period 1986 to 1997, the authors examined the role of CRM status as an immediate predictor of likely outcome, paying particular attention to its relationships with different surgeons and time periods.

Results: Of 586 patients on whom full clinical follow-up was obtained, 165 (28.2%) had CRM involvement by carcinoma on pathologic examination. Up to the end of 1998, 105 (17.9%) patients had developed local recurrence. A significantly higher proportion (38.2%) of CRM-positive patients developed local recurrence than CRM-negative ones (10.0%). Kaplan-Meier survival analysis showed significant improvements in survival for CRM-negative patients over CRM-positive patients. Survival analysis in relation to two gastrointestinal surgeons and a group of other surgeons showed survival improvements that paralleled a reduction in the rates of CRM involvement for the two gastrointestinal surgeons during the period of the study. No improvement in survival or reduction in rates of CRM involvement was seen in the group of other surgeons.

Conclusions: These results show that CRM status may be used as an immediate predictor of survival after rectal cancer surgery and serves as a useful indicator of the quality of surgery. The frequency of CRM involvement can be used both for overall surgical audit and for monitoring the value of training programs in improving rectal surgery by individual surgeons. Its use in the current MRC CR07 study is valid and the best indicator of a requirement for further local therapy.
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April 2002