Publications by authors named "Chris Cunningham"

100 Publications

Response to the comments on 'Minimally invasive organ-preserving approaches in the management of mesh erosion after laparoscopic ventral mesh rectopexy'.

Colorectal Dis 2021 Feb 1. Epub 2021 Feb 1.

Oxford University Hospitals NHS Foundation Trust, Oxford, UK.

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http://dx.doi.org/10.1111/codi.15551DOI Listing
February 2021

Study Protocol of a Randomized Controlled Trial of Home Modification to Prevent Home Fall Injuries in Houses with Māori Occupants.

Methods Protoc 2020 Oct 23;3(4). Epub 2020 Oct 23.

Research Centre for Hauora & Health, Massey University, Wellington 6021, New Zealand.

Worldwide, injuries due to falls in the home impose a substantial burden and merit considerable effort to find effective prevention measures. The current study is one of very few randomized controlled trials that assess the effectiveness of home modification for preventing falls. It is the first carried out with a minority or indigenous community and focused on reducing inequities. Just over 250 households in Aotearoa, New Zealand, with Māori occupants were recruited in two strata, 150 from the Wellington region and 100 from the Taranaki region. These were randomly allocated to equally sized treatment and control groups within the respective regions, the treatment group receiving a package of home modifications designed to prevent falls at the start of the study, and the control group receiving the package at the end of the study. Injury data came from the Accident Compensation Corporation, a state-owned no-fault injury insurer. This provided coverage of virtually all unintentional injuries requiring medical treatment. Matched injury claims were made available for analysis once all identifying fields had been removed. These data will be pooled with data for Māori households from the already-conducted Home Injury Prevention Intervention (HIPI) study, which tested an identical intervention on the general population. In the analysis, the primary outcome measure will be fall injury rates over time, comparing treatment and control households, adjusting for the stratum and prior falls in the household. A secondary measure will be the rates of specific injuries, which are most likely to be prevented by the package of modifications tested. We anticipate that the findings will provide robust evidence for effective injury prevention measures that can reduce an important contributor to health inequities for indigenous populations such as the Māori.
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http://dx.doi.org/10.3390/mps3040071DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7712143PMC
October 2020

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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http://dx.doi.org/10.1016/S2468-1253(21)00005-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7808901PMC
March 2021

Maintaining Standards in Colorectal Cancer Surgery During the Global Pandemic: A Cohort Study.

World J Surg 2021 03 9;45(3):655-661. Epub 2021 Jan 9.

Department of Colorectal Surgery, Oxford University Hospitals NHS Trust, Oxford, UK.

Aim: Cancer surgery in the COVID-19 pandemic presents many new challenges. For each patient, the risk of contracting COVID-19 during the perioperative period, with the potential for life-threatening sequelae (1), has to be weighed against the risk of delaying treatment. We assessed the response and short-term outcomes from elective colorectal cancer surgery during the pandemic at our institution.

Method: We report a prospective cohort study of all elective colorectal surgery cases performed at our Trust during the 11 weeks following the national UK lockdown on 23rd March 2020, compared with the same time period in 2019.

Results: Eighty-five colorectal operations were performed during the 2020 (COVID) time period, and 179 performed in the 2019 (non-COVID) time period. A significantly higher proportion of cases during the COVID period were cancer-related (66% vs 26%, p < 0.00001). There was no difference in length of hospital stay, complications or readmissions. There were no mortalities in either cohort. Among the cancer patients, there were no differences in TMN staging, R1 resection rate or lymph node yields. No elective patient tested positive for COVID-19 during the perioperative period.

Conclusion: At the height of the COVID pandemic, we maintained delivery the of high-quality elective colorectal cancer surgery, with no worsening of short-term outcomes and no compromise in the quality of cancer resections. Ongoing monitoring of this cohort is essential. The risks associated with COVID-19 will continue for some time, necessitating adaptive responses to maintain high-quality cancer services.
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http://dx.doi.org/10.1007/s00268-020-05928-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7796814PMC
March 2021

Local excision after (near) complete response of rectal cancer to neoadjuvant radiation: does it add value?

Int J Colorectal Dis 2021 Jan 6. Epub 2021 Jan 6.

Department of Colorectal Surgery, Oxford University Hospitals NHS Foundation Trust, Oxford, UK.

Purpose: Neoadjuvant radiotherapy is commonly used in rectal cancer. When used prior to radical surgery in locally advanced disease, up to one-quarter of patients have no residual cancer at surgery suggesting that radical surgery was unnecessary; those with complete clinical response may be managed on a rectal-preserving 'watch-and-wait' pathway. In those receiving radiotherapy for early stage cancer, local excision of small volume residual or recurrent tumour is possible, but its value is unclear.

Methods: Data were collected from two institutions (UK and Denmark) which maintain prospective databases on all patients undergoing local excision by transanal endoscopic microsurgery (TEM). The study group was all patients who had TEM after neoadjuvant radiation for rectal cancer over an 11-year period.

Results: Forty-five patients had TEM after neoadjuvant radiation, 18 after short course radiotherapy (SCRT) and 27 after chemoradiotherapy (CRT). Local recurrence occurred in 13 (29%) and distant metastases in 11 (24%). Complete pathological response was noted in 10 (22%), 28% after SCRT and 19% after CRT, p = 0.02. However, local recurrence still occurred in 60% of those with ypT0 after SCRT. The recurrence rate may be higher in those with residual disease at TEM compared with complete responders (40 vs 30%).

Conclusion: If complete response can be determined clinically, local excision of the scar does not confer benefit, but follow-up should be maintained. If there is regrowth or residual tumour at TEM, further recurrence is common, and the benefits of TEM may not outweigh the risks, except in those unsuitable for radical surgery.
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http://dx.doi.org/10.1007/s00384-020-03813-6DOI Listing
January 2021

Spatiotemporal analysis of human intestinal development at single-cell resolution.

Cell 2021 Feb 5;184(3):810-826.e23. Epub 2021 Jan 5.

Medical Research Council (MRC) Human Immunology Unit, MRC Weatherall Institute of Molecular Medicine (WIMM), John Radcliffe Hospital, University of Oxford, Oxford OX3 9DS, UK; Translational Gastroenterology Unit, John Radcliffe Hospital, Oxford OX3 9DU, UK. Electronic address:

Development of the human intestine is not well understood. Here, we link single-cell RNA sequencing and spatial transcriptomics to characterize intestinal morphogenesis through time. We identify 101 cell states including epithelial and mesenchymal progenitor populations and programs linked to key morphogenetic milestones. We describe principles of crypt-villus axis formation; neural, vascular, mesenchymal morphogenesis, and immune population of the developing gut. We identify the differentiation hierarchies of developing fibroblast and myofibroblast subtypes and describe diverse functions for these including as vascular niche cells. We pinpoint the origins of Peyer's patches and gut-associated lymphoid tissue (GALT) and describe location-specific immune programs. We use our resource to present an unbiased analysis of morphogen gradients that direct sequential waves of cellular differentiation and define cells and locations linked to rare developmental intestinal disorders. We compile a publicly available online resource, spatio-temporal analysis resource of fetal intestinal development (STAR-FINDer), to facilitate further work.
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http://dx.doi.org/10.1016/j.cell.2020.12.016DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7864098PMC
February 2021

Transition rates to cirrhosis and liver cancer by age, gender, disease and treatment status in Asian chronic hepatitis B patients.

Hepatol Int 2021 Feb 4;15(1):71-81. Epub 2021 Jan 4.

Division of Gastroenterology and Hepatology, Stanford University Medical Center, 780 Welch Road, CJ250K, Palo Alto, CA, 94304, USA.

Background: Increasing hepatitis-related mortality has reignited interest to fulfill the World Health Organization's goal of viral hepatitis elimination by 2030. However, economic barriers have enabled only 28% of countries to implement countermeasures. Given the high disease burden among Asians, we aimed to present age, sex, disease activity and treatment-specific annual progression rates among Asian chronic hepatitis B (CHB) patients to inform health economic modeling efforts and cost-effective public health interventions.

Methods: We analyzed 18,056 CHB patients from 36 centers across the U.S. and seven countries/regions of Asia Pacific (9530 treated; 8526 untreated). We used Kaplan-Meier methods to estimate annual incidence of cirrhosis and hepatocellular carcinoma (HCC). Active disease was defined by meeting the APASL treatment guideline criteria.

Results: Over a median follow-up of 8.55 years, there were 1178 incidences of cirrhosis and 1212 incidences of HCC (297 without cirrhosis, 915 with cirrhosis). Among the 8526 untreated patients (7977 inactive, 549 active), the annual cirrhosis and HCC incidence ranged from 0.26% to 1.30% and 0.04% to 3.80% in inactive patients, and 0.55 to 4.05% and 0.19 to 6.03% in active patients, respectively. Of the 9530 treated patients, the annual HCC rates ranged 0.03-1.57% among noncirrhotic males and 2.57-6.93% among cirrhotic males, with lower rates for females. Generally, transition rates increased with age, male sex, the presence of fibrosis/cirrhosis, and active disease and/or antiviral treatment.

Conclusion: Using data from a large and diverse real-world cohort of Asian CHB patients, the study provided detailed annual transition rates to inform practice, research and public health planning.
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http://dx.doi.org/10.1007/s12072-020-10113-2DOI Listing
February 2021

Local excision after polypectomy for rectal polyp cancer: when is it worthwhile?

Colorectal Dis 2020 Dec 11. Epub 2020 Dec 11.

Department of Colorectal Surgery, Oxford University Hospitals NHS Foundation Trust, Oxford, UK.

Aim: The optimal management of a polyp cancer that has been removed endoscopically is unclear. Further local excision is often advocated to remove the polyp stalk or scar or to ensure clear margins, but the benefit of this is unclear. The aim of this paper is to determine whether the indications for further local excision can be better defined.

Method: Data were collected from two institutions (in UK and Denmark) which maintain prospective databases to collect information on all patients undergoing transanal endoscopic microsurgery (TEM). The study group was all patients who had a TEM after macroscopically complete polypectomy for rectal cancer. Data covering an 11-year period were analysed.

Results: Sixty three patients had TEM with no residual cancer after macroscopically complete polypectomy. Residual adenoma was found in 23 (37%). A postpolypectomy endoscopy had not detected the residual adenoma in three. Malignant local recurrence occurred in five patients (8%) and distant metastases in another two (3%). Recurrence occurred in 4/23 (17%) when there was residual adenoma in the TEM specimen and in 3/40 (7.5%) where there was scar only, although this did not reach significance. In two instances recurrence was around 10 years after TEM. Those with residual adenoma at TEM tended to have poorer survival.

Conclusion: Further local excision often reveals no residual cancer despite microscopically involved polypectomy margins. Careful endoscopy is required to assess the polypectomy site as residual tumour can be missed. In the absence of residual adenoma, TEM does not appear to be of benefit, although a small risk of recurrence exists.
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http://dx.doi.org/10.1111/codi.15480DOI Listing
December 2020

Patients' Perception of Long-term Outcome after Laparoscopic Ventral Mesh Rectopexy; Single Tertiary Center Experience.

Ann Surg 2020 Nov 9. Epub 2020 Nov 9.

Department of Colorectal Surgery, Oxford University Hospitals NHS Foundation Trust, Oxford, United Kingdom.

Objective: To assess patients' long-term outcome and satisfaction after laparoscopic ventral mesh rectopexy (LVMR).

Summary Background Data: Data on the long-term outcome and satisfaction of patients undergoing LVMR are limited.

Methods: Patients who underwent LVMR between 2004 and 2017 were identified from a prospectively maintained database. We attempted to contact all patients by telephone for an interview using a standardized questionnaire to record pre-LVMR symptoms, long-term outcome, and overall satisfaction.

Results: Total number of patients who underwent LVMR was 848 and 99(12%) were deceased at follow-up (FU). In the end, 544(64%) patients were contacted successfully and 478(56%) were able to complete the questionnaire. Median time elapsed since surgery was 7 years and mean age was 62 years. Patients' reported pre-operative symptoms were obstructed defecation syndrome (ODS) in 40%, fecal incontinence (FI) in 22%, combination of ODS and FI in 21% and other conditions in 17%. Bowel symptoms were reported as improved by 69% of patients and worse by 12%. Pelvic pain was reported to be improved in 47% of the patients after LVMR but new onset of pelvic pain appeared in 15%. Sexual function was reported to be better and worse with equal frequency. Overall, 63% of the patients were satisfied with the outcome and 76% would recommend this procedure to others with similar symptoms.

Conclusion: LVMR offers acceptable long-term outcomes and satisfaction. There is a mixed impact on pelvic pain and sexual function which requires careful consideration in counselling patients for this procedure.
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http://dx.doi.org/10.1097/SLA.0000000000004559DOI Listing
November 2020

A routine third trimester growth ultrasound in the obese pregnant woman does not reliably identify fetal growth abnormalities: A retrospective cohort study.

Aust N Z J Obstet Gynaecol 2021 02 24;61(1):116-122. Epub 2020 Oct 24.

Women's and Children's Division, Joan Kirner Women's and Children's at Sunshine Hospital, Western Health, Melbourne, Victoria, Australia.

Background: In response to the challenges of assessing fetal growth in obese women, guidelines recommend routine third trimester ultrasound scans.

Aim: The aim of this study was to assess the diagnostic performance of this routine scan in obese women (body mass index (BMI) ≥ 35 kg/m ).

Methods: A retrospective cohort study of 1008 pregnancies with maternal BMI ≥ 35 kg/m born after 37 weeks gestation at a Victorian hospital from 2015 to 2017. Multiple pregnancies and those affected by diabetes were excluded. Growth ultrasounds were performed between 34 + 0 and 36 + 6 weeks gestation. Sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) for the detection of large for gestational age (LGA > 90%) and small for gestational age (SGA < 10%) were calculated using ultrasound estimated fetal weight (EFW) or abdominal circumference (AC) and compared with gestational age and gender-based birthweight percentiles.

Results: Using EFW, sensitivity for detecting SGA at birth was 8.1% (six of 74) with a PPV of 100%. Sensitivity for detecting LGA at birth was 61.0% (119 of 195), PPV 54.8%. Sensitivity, specificity, PPV and NPV percentages were all lower using AC. Only 40% of actual birthweight percentiles (405/1008) were within ±10 percentiles of their growth ultrasound EFW percentile.

Conclusion: The performance of a routine third trimester ultrasound in women with BMI ≥ 35 kg/m suggests limited utility in helping identify aberrant fetal growth. This has important implications for the management of obese pregnant women.
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http://dx.doi.org/10.1111/ajo.13256DOI Listing
February 2021

Incidence, Factors, and Patient-Level Data for Spontaneous HBsAg Seroclearance: A Cohort Study of 11,264 Patients.

Clin Transl Gastroenterol 2020 Sep;11(9):e00196

1Department of Medicine, Stanford University Medical Center, Palo Alto, California, USA; 2Division of Gastroenterology and Hepatology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan; 3Department of Hepatology, Toranomon Hospital, Tokyo, Japan; 4Research Centre for Maori Health and Development, Massey University, Wellington, New Zealand; 5The Hepatitis Foundation of New Zealand, Whakatane, New Zealand; 6Department of Medicine, The University of Hong Kong, Hong Kong, China; 7Division of Translational Research, Taipei Veterans General Hospital, Taipei City, Taiwan; 8Department of Internal Medicine and Liver Research Institute, Seoul National University Hospital, Seoul, Korea; 9San Jose Gastroenterology, San Jose, California, USA; 10Faculty of Medicine and Public Health, HRH Princess Chulabhorn College of Medical Science, Chulabhorn Royal Academy, Bangkok, Thailand; 11Hepatobiliary Section, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan; 12Center for Liver Research, School of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan; 13Center for Cancer Research, Kaohsiung Medical University, Kaohsiung, Taiwan; 14Research Institute for Hepatology, Toranomon Hospital, Tokyo, Japan; 15Palo Alto Medical Foundation, Mountain View Division, Palo Alto, California, USA; 16Chinese Hospital, San Francisco, California, USA; 17School of Nursing, University of California, San Francisco, San Francisco, California, USA; 18Department of Medicine, Faculty of Medicine, Siriraj Hospital, Mahidol University, Bangkok, Thailand; 19New Zealand Liver Transplant Unit, Auckland City Hospital, Auckland, New Zealand; 20Department of Medicine, University of Auckland, Auckland, New Zealand; 21Division of Gastroenterology and Hepatology, Veterans Affairs Palo Alto Health Care System, Palo Alto, California, USA; 22College of Public Health, China Medical University, Taichung, Taiwan; 23Division of Gastroenterology and Hepatology, University of Michigan, Ann Arbor, Michigan, USA; 24Graduate Institute of Clinical Medicine, College of Medicine, National Taiwan University, Taipei, Taiwan; 25Genomics Research Center, Academia Sinica, Taipei, Taiwan; 26Institute of Clinical Medicine, National Yang-Ming University, Taipei, Taiwan.

Introduction: Spontaneous hepatitis B surface antigen (HBsAg) seroclearance, the functional cure of hepatitis B infection, occurs rarely. Prior original studies are limited by insufficient sample size and/or follow-up, and recent meta-analyses are limited by inclusion of only study-level data and lack of adjustment for confounders to investigate HBsAg seroclearance rates in most relevant subgroups. Using a cohort with detailed individual patient data, we estimated spontaneous HBsAg seroclearance rates through patient and virologic characteristics.

Methods: We analyzed 11,264 untreated patients with chronic hepatitis B with serial HBsAg data from 4 North American and 8 Asian Pacific centers, with 1,393 patients with HBsAg seroclearance (≥2 undetectable HBsAg ≥6 months apart) during 106,192 person-years. The annual seroclearance rate with detailed categorization by infection phase, further stratified by hepatitis B e antigen (HBeAg) status, sex, age, and quantitative HBsAg (qHBsAg), was performed.

Results: The annual seroclearance rate was 1.31% (95% confidence interval: 1.25-1.38) and over 7% in immune inactive patients aged ≥55 years and with qHBsAg <100 IU/mL. The 5-, 10-, 15-, and 20-year cumulative rates were 4.74%, 10.72%, 18.80%, and 24.79%, respectively. On multivariable analysis, male (adjusted hazard ratio [aHR] = 1.66), older age (41-55 years: aHR = 1.16; >55 years: aHR = 1.21), negative HBeAg (aHR = 6.34), and genotype C (aHR = 1.82) predicted higher seroclearance rates, as did lower hepatitis B virus DNA and lower qHBsAg (P < 0.05 for all), and inactive carrier state.

Discussion: The spontaneous annual HBsAg seroclearance rate was 1.31%, but varied from close to zero to about 5% among most chronic hepatitis B subgroups, with older, male, HBeAg-negative, and genotype C patients with lower alanine aminotransferase and hepatitis B virus DNA, and qHBsAg independently associated with higher rates (see Visual Abstract, Supplementary Digital Content 2, http://links.lww.com/CTG/A367).
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http://dx.doi.org/10.14309/ctg.0000000000000196DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7494149PMC
September 2020

Laparoscopic Colorectal Surgery Outcomes Improved After National Training Program (LAPCO) for Specialists in England.

Ann Surg 2020 Oct 19. Epub 2020 Oct 19.

Department of Colorectal Surgery, Plymouth Hospitals NHS Trust, Plymouth.

Objective: To examine the impact of The National Training Programme for Laparoscopic Colorectal Surgery (Lapco) on the rate of laparoscopic surgery and clinical outcomes of cases performed by Lapco surgeons after completion of training.

Summery Background Data: Lapco provided competency-based supervised clinical training for specialist colorectal surgeons in England.

Methods: We compared the rate of laparoscopic surgery, mortality and morbidity for colorectal cancer resections by Lapco delegates and non-Lapco surgeons in 3-year periods preceding and following Lapco using difference in differences analysis. The changes in the rate of post-Lapco laparoscopic surgery with the Lapco sign-off competency assessment and in-training global assessment scores were examined using risk-adjusted cumulative sum to determine their predictive clinical validity with predefined competent scores of 3 and 5 respectively.

Results: 108 Lapco delegates performed 4586 elective colorectal resections pre-Lapco and 5115 post-Lapco while non-Lapco surgeons performed 72930 matched cases. Lapco delegates had a 37.8% increase in laparoscopic surgery which was greater than non-Lapco surgeons by 20.9% (95% CI, 18.5 to 23.3, p<0.001) with a relative decrease in 30-day mortality by -1.6% (95% CI, -3.4 to -0.2, p = 0.039) and 90-day mortality by -2.3% (95% CI, -4.3 to -0.4, p = 0.018). The change point of risk-adjusted cumulative sum was 3.12 for competency assessment tool and 4.74 for global assessment score whereas laparoscopic rate increased from 44% to 66% and 40% to 56% respectively.

Conclusions: Lapco increased the rate of laparoscopic colorectal cancer surgery and reduced mortality and morbidity in England. In-training competency assessment tools predicted clinical performance after training.
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http://dx.doi.org/10.1097/SLA.0000000000004584DOI Listing
October 2020

Chronic hepatitis B infection-an unmet medical need in New Zealand 35 years after universal neonatal vaccination.

N Z Med J 2020 07 31;133(1519):70-80. Epub 2020 Jul 31.

Research Centre for Māori Health & Development, Massey University, Wellington.

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July 2020

Quality of life after rectal-preserving treatment of rectal cancer.

Eur J Surg Oncol 2020 11 22;46(11):2050-2056. Epub 2020 Jul 22.

Department of Colorectal Surgery, Oxford University Hospitals NHS Foundation Trust, UK.

Aim: Rectal-preserving strategies for managing rectal cancer are becoming more common for selected groups of patients. Oncological outcomes are similar, so long as patients are closely followed, and any local recurrence detected and managed promptly. Functional outcomes are now of increasing importance so patients can be appropriately counselled prior to treatment. We examine functional outcomes in patients managed by multimodal organ-preservation approaches allowing comparison of the full range of strategies.

Materials And Methods: Patients attending for surveillance after any of four rectal-preserving treatments for rectal cancer (radiotherapy [RT], local excision [LE], RT then LE or LE then RT) were asked to complete a questionnaire assessing general quality of life and bowel, urinary and sexual function.

Results: 100 patients completed questionnaires: 34 managed by neoadjuvant RT followed by 'watch and wait', 40 by LE, and 26 who had composite treatment (18 LE + RT and eight RT + LE). Questionnaires were completed a median of 10 months (IQ range 6-33) following treatment. The LE only group tended to have better bowel function, while the composite groups fared worse; significant differences were noted in LARS and some bowel symptoms scores.

Conclusion: Bowel function appears better after LE alone compared with treatment strategies involving RT, and composite treatments have an additive effect on outcome impairment. Overall quality of life outcomes are good, despite the ongoing requirement for surveillance. As these treatments become more common it is important that patients can be better informed before deciding on a management pathway.
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http://dx.doi.org/10.1016/j.ejso.2020.07.018DOI Listing
November 2020

Correction to: Comparison of two invitation-based methods for human papillomavirus (HPV) self-sampling with usual care among un- and under-screened Māori, Pacific and Asian women: study protocol for a randomised controlled community trial to examine the effect of self-sampling on participation in cervical-cancer screening.

BMC Cancer 2020 02 27;20(1):163. Epub 2020 Feb 27.

Centre for Public Health Research, Massey University, Wellington, New Zealand.

Following publication of the original article [1], the authors reported an error in the authorship list associated with the paper. Georgina McPherson has therefore been added.
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http://dx.doi.org/10.1186/s12885-020-6671-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7047358PMC
February 2020

Comparison of two invitation-based methods for human papillomavirus (HPV) self-sampling with usual care among un- and under-screened Māori, Pacific and Asian women: study protocol for a randomised controlled community trial to examine the effect of self-sampling on participation in cervical-cancer screening.

BMC Cancer 2019 12 9;19(1):1198. Epub 2019 Dec 9.

Centre for Public Health Research, Massey University, Wellington, New Zealand.

Background: Māori, Pacific and Asian women in New Zealand have lower cervical-cancer screening rates than European women, and there are persistent inequities in cervical cancer outcomes for Māori and Pacific women. Innovative ways to address access barriers are required. New Zealand is transitioning to screening with human papillomavirus (HPV) DNA testing, which could allow women themselves, rather than a clinician, to take the sample. Internationally, self-sampling has been found to increase screening participation rates. The aim of this open-label community-based randomised controlled trial is to investigate whether self-sampling increases screening participation among un- and under-screened Māori, Pacific and Asian women in New Zealand.

Methods/design: We aim to invite at least 3550 un- or under-screened (≥5 years overdue) Māori, Pacific and Asian women (1050, 1250, 1250 respectively), aged 30-69 years, for screening. The three study arms are: usual care in which women are invited to attend a clinic for a standard clinician-collected cytology test; clinic-based self-sampling in which women are invited to take a self-sample at their usual general practice; and mail-out self-sampling in which women are mailed a kit and invited to take a self-sample at home. Women will be randomised 3:3:1 to the clinic and mail-out self-sampling groups, and usual care. There is also a nested sub-study in which non-responding women in all allocation groups, when they subsequently present to the clinic for other reasons, are offered clinic or home-kit self-sampling. The primary outcome will be the proportion of women who participate (by taking a self-sample or cytology test).

Discussion: This trial is the first to evaluate the effectiveness of mailed self-sampling in New Zealand and will be one of the first internationally to evaluate the effectiveness of opportunistic in-clinic invitations for self-sampling. The trial will provide robust evidence on the impact on participation proportions from different invitation approaches for HPV self-sampling in New Zealand un- and under-screened Māori, Pacific and Asian women.

Trial Registration: ANZCTR Identifier: ACTRN12618000367246 (date registered 12/3/2018) https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=371741&isReview=true; UTN: U1111-1189-0531.
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http://dx.doi.org/10.1186/s12885-019-6401-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6902319PMC
December 2019

Impact of Suture Type on Erosion Rate After Laparoscopic Ventral Mesh Rectopexy: A Case-Matched Study.

Dis Colon Rectum 2019 12;62(12):1512-1517

Department of Colorectal Surgery, Churchill Hospital, University Hospitals of Oxford, Oxford, United Kingdom.

Background: There has been increasing concern and scrutiny in the use of mesh for certain pelvic organ prolapse procedures. However, mesh erosion was often associated with sites of suture fixation of the mesh to the rectum or vagina. Thus, in response to this finding, we replaced our suture material with absorbable monofilament suture.

Objective: The purpose of this study was to compare the rates of mesh-related complications after laparoscopic ventral mesh rectopexy, according to the type of suture used in fixation of mesh.

Design: This was retrospective cohort study.

Settings: This study was performed at a high-volume, tertiary care center. It was conducted using a prospective database including patients who underwent laparoscopic ventral mesh rectopexy over a 7-year period.

Patients: A total of 495 cases were included; 296 (60%) laparoscopic ventral mesh rectopexies were performed using a nonabsorbable suture compared with 199 (40%) with an absorbable suture in a case-matched analysis. In addition, 151 cases of laparoscopic ventral mesh rectopexy with nonabsorbable were matched based on age, sex, and time of follow-up, with an equal number of patients using absorbable monofilament suture.

Main Outcomes Measures: Primary outcome was symptomatic mesh erosion after rectopexy. Secondary outcomes included other mesh-related complications and/or reoperations.

Results: The erosion rate was 2% (6/495) in the nonabsorbable suture group, including 4 erosions into the rectum and 2 into the vagina. There was no erosion in the group with absorbable suture. This difference was maintained after matching: after a median follow-up of 6 (12) months, there was no erosion in the absorbable suture group versus 3.3% erosion (n = 5) in the nonabsorbable suture group (p = 0.03).

Limitations: This study was limited by its retrospective design.

Conclusions: Mesh-related complications are reduced using absorbable sutures compared with nonabsorbable sutures when performing laparoscopic ventral mesh rectopexy with synthetic mesh without an increase in rectopexy failures. See Video Abstract at http://links.lww.com/DCR/B49. IMPACTO DEL TIPO DE SUTURA EN LA TASA DE EROSIóN DESPUéS DE LA RECTOPEXIA VENTRAL LAPAROSCóPICA CON MALLA: UN ESTUDIO DE CASOS EMPAREJADOS: Ha habido una creciente preocupación y escrutinio en el uso de la malla para ciertos procedimientos de prolapso de órganos pélvicos. Sin embargo, la erosión de la malla a menudo se asoció con sitios de fijación de sutura de la malla al recto o la vagina. Por lo tanto, en respuesta a este hallazgo, reemplazamos nuestro material de sutura con sutura de monofilamento absorbible.Comparar las tasas de complicaciones relacionadas con la malla después de la rectopexia laparoscópica de malla ventral, de acuerdo al tipo de sutura utilizada en la fijación de la malla.Este fue un estudio de cohorte retrospectivo.Este estudio se realizó en un centro de atención de tercer nivel de alto volumen. Se realizó utilizando una base de datos prospectiva que incluía pacientes que se sometieron a una rectopexia de malla ventral laparoscópica durante un período de 7 años.Se incluyeron un total de 495 casos; 296 (60%) rectopexias de malla ventral laparoscópica utilizando una sutura no reabsorbible en comparación con 199 (40%) con una sutura absorbible en un análisis de casos emparejados. Además, 151 casos de rectopexia ventral laparoscópica con malla no absorbible se emparejaron según la edad, el sexo y el tiempo de seguimiento con un número igual de pacientes que usaban sutura de monofilamento absorbible.La medida de resultado primaria fue la erosión sintomática de la malla después de la rectopexia. La medida de resultado secundarias incluyeron otras complicaciones y/o reoperaciones relacionadas con la malla.La tasa de erosión fue del 2% (6/495) en el grupo de sutura no absorbible; 4 erosiones en el recto y 2 en la vagina. No hubo erosión en el grupo con sutura absorbible. Esta diferencia se mantuvo después del emparejamiento: después de una mediana de seguimiento de 6 (12) meses, no hubo erosión en el grupo de sutura absorbible versus 3.3% de erosión (n = 5) en el grupo de sutura no absorbible (p = 0.03).Este estudio estuvo limitado por su diseño retrospectivo.Las complicaciones relacionadas con la malla se reducen utilizando suturas absorbibles en comparación con las suturas no absorbibles cuando se realiza la rectopexia de malla ventral laparoscópica con malla sintética, sin un aumento en los fracasos de rectopexia. Vea el Resumen del Video en http://links.lww.com/DCR/B49.
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http://dx.doi.org/10.1097/DCR.0000000000001510DOI Listing
December 2019

Exploiting differential Wnt target gene expression to generate a molecular biomarker for colorectal cancer stratification.

Gut 2020 06 28;69(6):1092-1103. Epub 2019 Sep 28.

Intestinal Stem Cell Biology Lab, Wellcome Trust Centre Human Genetics, University of Oxford, Oxford, UK

Objective: Pathological Wnt pathway activation is a conserved hallmark of colorectal cancer. Wnt-activating mutations can be divided into: i) ligand-independent (LI) alterations in intracellular signal transduction proteins (, β-catenin), causing constitutive pathway activation and ii) ligand-dependent (LD) mutations affecting the synergistic R-Spondin axis (, -fusions) acting through amplification of endogenous Wnt signal transmembrane transduction. Our aim was to exploit differential Wnt target gene expression to generate a mutation-agnostic biomarker for LD tumours.

Design: We undertook harmonised multi-omic analysis of discovery (n=684) and validation cohorts (n=578) of colorectal tumours collated from publicly available data and the Stratification in Colorectal Cancer Consortium. We used mutation data to establish molecular ground truth and subdivide lesions into LI/LD tumour subsets. We contrasted transcriptional, methylation, morphological and clinical characteristics between groups.

Results: Wnt disrupting mutations were mutually exclusive. Desmoplastic stromal upregulation of may compensate for absence of epithelial mutation in a subset of stromal-rich tumours. Key Wnt negative regulator genes were differentially expressed between LD/LI tumours, with targeted hypermethylation of some genes (, ) occurring even in CIMP-negative LD cancers. mRNA expression was used as a discriminatory molecular biomarker to distinguish LD/LI tumours (area under the curve >0.93).

Conclusions: Epigenetic suppression of appropriate Wnt negative feedback loops is selectively advantageous in LD tumours and differential expression in LD/LI lesions can be exploited as a molecular biomarker. Distinguishing between LD/LI tumour types is important; patients with LD tumours retain sensitivity to Wnt ligand inhibition and may be stratified at diagnosis to clinical trials of Porcupine inhibitors.
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http://dx.doi.org/10.1136/gutjnl-2019-319126DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7212029PMC
June 2020

Measured collagen fibril response to arterial inflation using SAXS.

Int J Biol Macromol 2019 Sep 8;137:1020-1029. Epub 2019 Jul 8.

School of Engineering and Advanced Technology, Massey University, Palmerston North 4472, New Zealand. Electronic address:

Arteries are elastic structures containing both elastin and collagen. While the high content of elastin is understood to be important for the elasticity of arteries with systolic and diastolic pressure pulses, the role of collagen in the elastic properties of arteries is less understood. Here we use small angle X-ray scattering to investigate the changes in arrangement of collagen fibrils and the strain experienced by collagen fibrils as arteries are inflated. Collagen fibrils re-orient to become more aligned in both the annular direction and radially as arteries inflate. With arterial pressures up to 32 kPa there is no observable increase in D-spacing of the collagen fibrils (<0.1%) indicating that there is no extension of straightened fibrils and therefore no change in stress on the collagen fibrils. This is in contrast to tissue such as skin where stress of the tissue may induce strains in collagen fibrils of >6%. In arteries the collagen fibril elasticity (strain at the scale of fibrils) is not the main elastic component of the arterial walls. This indicates that wall elasticity is dominated by other factors such as the structural arrangement of the collagen fibers.
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http://dx.doi.org/10.1016/j.ijbiomac.2019.07.061DOI Listing
September 2019

Lateral Nodal Features on Restaging Magnetic Resonance Imaging Associated With Lateral Local Recurrence in Low Rectal Cancer After Neoadjuvant Chemoradiotherapy or Radiotherapy.

JAMA Surg 2019 09 18;154(9):e192172. Epub 2019 Sep 18.

Department of Surgery, Amsterdam University Medical Centers, location VUmc, Amsterdam, the Netherlands.

Importance: Previously, it was shown in patients with low rectal cancer that a short-axis (SA) lateral node size of 7 mm or greater on primary magnetic resonance imaging (MRI) resulted in a high lateral local recurrence (LLR) rate after chemoradiotherapy or radiotherapy ([C]RT) with total mesorectal excision (TME) and that this risk was lowered by a lateral lymph node dissection (LLND). The role of restaging MRI after (C)RT with regard to LLR risk and which specific patients might benefit from an LLND is not fully understood.

Objective: To determine the factors on primary and restaging MRI that are associated with LLR in low rectal cancer after (C)RT and to formulate specific guidelines on which patients might benefit from an LLND.

Design, Setting, And Participants: In this retrospective, multicenter, pooled cohort study, patients who underwent surgery for cT3 or cT4 low rectal cancer with a curative intent from 12 centers in 7 countries from January 2009 to December 2013 were included. All patients' MRIs were rereviewed according to a standardized protocol, with specific attention to lateral nodal features. The original cohort included 1216 patients. For this study, patients who underwent (C)RT and had a restaging MRI were selected, leaving 741 for analyses across 10 institutions, including 651 who underwent (C)RT with TME and 90 who underwent (C)RT with TME and LLND.

Main Outcomes And Measures: The main purpose was to identify the factors on primary and restaging MRI associated with LLR after (C)RT with TME. Whether high-risk patients might benefit in terms of LLR reduction from an LLND was also studied.

Results: Of the 741 included patients, 480 (64.8%) were male, and the mean (SD) age was 60.4 (12.0) years. An SA lateral node size of 7 mm or greater on primary MRI resulted in a 5-year LLR rate of 17.9% after (C)RT with TME. At 3 years, there were no LLRs in 28 patients (29.2%) with lateral nodes that were 4 mm or less on restaging MRI. Nodes that were 7 mm or greater on primary MRI and greater than 4 mm on restaging MRI in the internal iliac compartment resulted in a 5-year LLR rate of 52.3%, significantly higher compared with nodes in the obturator compartment of that size (9.5%; hazard ratio, 5.8; 95% CI, 1.6-21.3; P = .003). Compared with (C)RT with TME alone, treatment with (C)RT with TME and LLND in these unresponsive internal nodes resulted in a significantly lower LLR rate of 8.7% (hazard ratio, 6.2; 95% CI, 1.4-28.5; P = .007).

Conclusions And Relevance: Restaging MRI is important in clinical decision making in lateral nodal disease. In patients with shrinkage of lateral nodes from an SA node size of 7 mm or greater on primary MRI to an SA node size of 4 mm or less on restaging MRI, which occurs in about 30% of cases, LLND can be avoided. However, persistently enlarged nodes in the internal iliac compartment indicate an extremely high risk of LLR, and an LLND lowered LLR in these cases.
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http://dx.doi.org/10.1001/jamasurg.2019.2172DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6613303PMC
September 2019

Carbon Dioxide Embolism Associated With Transanal Total Mesorectal Excision Surgery: A Report From the International Registries.

Dis Colon Rectum 2019 07;62(7):794-801

Department of Surgery, Oncologic and Lower GI Surgery, Amsterdam University Medical Centers, University of Amsterdam, Amsterdam, the Netherlands.

Background: Carbon dioxide embolus has been reported as a rare but clinically important risk associated with transanal total mesorectal excision surgery. To date, there exists limited data describing the incidence, risk factors, and management of carbon dioxide embolus in transanal total mesorectal excision.

Objective: This study aimed to obtain data from the transanal total mesorectal excision registries to identify trends and potential risk factors for carbon dioxide embolus specific to this surgical technique.

Design: Contributors to both the LOREC and OSTRiCh transanal total mesorectal excision registries were invited to report their incidence of carbon dioxide embolus. Case report forms were collected detailing the patient-specific and technical factors of each event.

Settings: The study was conducted at the collaborating centers from the international transanal total mesorectal excision registries.

Main Outcome Measures: Characteristics and outcomes of patients with carbon dioxide embolus associated with transanal mesorectal excision were measured.

Results: Twenty-five cases were reported. The incidence of carbon dioxide embolus during transanal total mesorectal excision is estimated to be ≈0.4% (25/6375 cases). A fall in end tidal carbon dioxide was noted as the initial feature in 22 cases, with 13 (52%) developing signs of hemodynamic compromise. All of the events occurred in the transanal component of dissection, with mean (range) insufflation pressures of 15 mm Hg (12-20 mm Hg). Patients were predominantly (68%) in a Trendelenburg position, between 30° and 45°. Venous bleeding was reported in 20 cases at the time of carbon dioxide embolus, with periprostatic veins documented as the most common site (40%). After carbon dioxide embolus, 84% of cases were completed after hemodynamic stabilization. Two patients required cardiopulmonary resuscitation because of cardiovascular collapse. There were no deaths.

Limitations: This is a retrospective study surveying reported outcomes by surgeons and anesthetists.

Conclusions: Surgeons undertaking transanal total mesorectal excision must be aware of the possibility of carbon dioxide embolus and its potential risk factors, including venous bleeding (wrong plane surgery), high insufflation pressures, and patient positioning. Prompt recognition and management can limit the clinical impact of such events. See Video Abstract at http://links.lww.com/DCR/A961.
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http://dx.doi.org/10.1097/DCR.0000000000001410DOI Listing
July 2019

Role of nerve block as a diagnostic tool in pudendal nerve entrapment.

ANZ J Surg 2019 06 15;89(6):695-699. Epub 2019 May 15.

Department of Colorectal Surgery, Oxford University Hospital NHS Trust, Oxford, UK.

Background: Pudendal nerve entrapment is a disabling condition which is difficult to diagnose and treat. Nantes criteria include the requirement of positive anaesthetic pudendal nerve block that is widely used to allow identification of patients likely to benefit from the definitive but invasive pudendal nerve release. This study aimed to determine if pudendal nerve blockade under general anaesthesia could diagnose and temporarily treat pudendal nerve entrapment in patients suffering from chronic pelvic/perineal pain and/or organ dysfunction.

Methods: This retrospective analysis of a prospectively maintained database examined the outcomes of all recipients of diagnostic pudendal nerve block in a quaternary referral centre between 2012 and 2017. Primary outcome was relief of perineal pain (transient or permanent). Secondary outcomes were demographics, referral patterns for definitive procedure and complication rates. Statistical analysis was performed using SPSS v 24.

Results: A total of 77 patients were included in the study. Mean age was 57.27 ± 13.55 years. Majority were females (n = 62, 80.5%). Relief of pain was experienced by 47 of 76 (68.1%) patients after initial injection. Complication rate of injection was 3.9% (n = 3) which in all cases was unilateral lower limb paraesthesia. Of the 37 patients (52.9%) referred, 20 underwent surgical decompression with 12 (60%) being successful.

Conclusion: Pudendal nerve injection is a safe and simple procedure that can provide accurate diagnosis and transient relief from this chronic and debilitating problem. This technique helps to isolate patients suitable for pudendal nerve decompression which offers high success rates.
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http://dx.doi.org/10.1111/ans.15275DOI Listing
June 2019

Accelerating the elimination of viral hepatitis for Indigenous peoples.

Authors:
Chris Cunningham

Lancet Gastroenterol Hepatol 2019 02;4(2):93-94

Research Centre for Maori Health and Development, Massey University, Wellington, New Zealand; The Hepatitis Foundation of New Zealand, Whakatane, New Zealand. Electronic address:

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http://dx.doi.org/10.1016/S2468-1253(18)30412-6DOI Listing
February 2019

Neoadjuvant (Chemo)radiotherapy With Total Mesorectal Excision Only Is Not Sufficient to Prevent Lateral Local Recurrence in Enlarged Nodes: Results of the Multicenter Lateral Node Study of Patients With Low cT3/4 Rectal Cancer.

J Clin Oncol 2019 01 7;37(1):33-43. Epub 2018 Nov 7.

12 Catharina Hospital, Eindhoven, the Netherlands.

Purpose: Improvements in magnetic resonance imaging (MRI), total mesorectal excision (TME) surgery, and the use of (chemo)radiotherapy ([C]RT) have improved local control of rectal cancer; however, we have been unable to eradicate local recurrence (LR). Even in the face of TME and negative resection margins (R0), a significant proportion of patients with enlarged lateral lymph nodes (LLNs) suffer from lateral LR (LLR). Japanese studies suggest that the addition of an LLN dissection (LLND) could reduce LLR. This multicenter pooled analysis aims to ascertain whether LLNs actually pose a problem and whether LLND results in fewer LLRs.

Patients And Methods: Data from 1,216 consecutive patients with cT3/T4 rectal cancers up to 8 cm from the anal verge who underwent surgery in a 5-year period were collected. LLND was performed in 142 patients (12%). MRIs were re-evaluated with a standardized protocol to assess LLN features.

Results: On pretreatment MRI, 703 patients (58%) had visible LLN, and 192 (16%) had a short axis of at least 7 mm. One hundred eight patients developed LR (5-year LR rate, 10.0%), of which 59 (54%) were LLRs (5-year LLR rate, 5.5%). After multivariable analyses, LLNs with a short axis of at least 7 mm resulted in a significantly higher risk of LLR (hazard ratio, 2.060; P = .045) compared with LLNs of less than 7 mm. In patients with LLNs at least 7 mm, (C)RT plus TME plus LLND resulted in a 5-year LLR of 5.7%, which was significantly lower than that in patients who underwent (C)RT plus TME (5-year LLR, 19.5%; P = .042).

Conclusion: LLR is still a significant problem after (C)RT plus TME in LLNs with a short axis at least 7 mm on pretreatment MRI. The addition of LLND results in a significantly lower LLR rate.
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http://dx.doi.org/10.1200/JCO.18.00032DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6366816PMC
January 2019

Transanal total mesorectal excision (TaTME) versus laparoscopic TME for MRI-defined low rectal cancer: a propensity score-matched analysis of oncological outcomes.

Surg Endosc 2019 08 22;33(8):2459-2467. Epub 2018 Oct 22.

Department Surgery, Amsterdam University Medical Centers, University of Amsterdam, Meibergdreef 9, 1105 AZ, Amsterdam, The Netherlands.

Background: While a shift to minimally invasive techniques in rectal cancer surgery has occurred, non-inferiority of laparoscopy in terms of oncological outcomes has not been definitely demonstrated. Transanal total mesorectal excision (TaTME) has been pioneered to potentially overcome difficulties experienced when operating with a pure abdominal approach deep down in the pelvis. This study aimed to compare short-term oncological results of TaTME versus laparoscopic TME (lapTME), based on a strict anatomical definition for low rectal cancer on MRI.

Methods: From June 2013, all consecutive TaTME cases were included and compared to lapTME in a single institution. Propensity score-matching was performed for nine relevant factors. Primary outcome was resection margin involvement (R1), secondary outcomes included intra- and post-operative outcomes.

Results: After matching, forty-one patients were included in each group; no significant differences were observed in patient and tumor characteristics. The resection margin was involved in 5 cases (12.2%) in the laparoscopic group, versus 2 (4.9%) TaTME cases (P = 0.432). The TME specimen quality was complete in 84.0% of the laparoscopic cases and in 92.7% of the TaTME cases (P = 0.266). Median distance to the circumferential resection margin (CRM) was 5 mm in lapTME and 10 mm in TaTME (P = 0.065). Significantly more conversions took place in the laparoscopic group, 9 (22.0%) compared to none in the TaTME group (P < 0.001). Other clinical outcomes did not show any significant differences between the two groups.

Conclusion: This is the first study to compare results of TaTME with lapTME in a highly selected patient group with MRI-defined low rectal tumors. A significant decrease in R1 rate could not be demonstrated, although conversion rate was significantly lower in this TaTME cohort.
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http://dx.doi.org/10.1007/s00464-018-6530-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6647375PMC
August 2019

Aiming for the elimination of viral hepatitis in Australia, New Zealand, and the Pacific Islands and Territories: Where are we now and barriers to meeting World Health Organization targets by 2030.

J Gastroenterol Hepatol 2019 Jan 27;34(1):40-48. Epub 2018 Sep 27.

Disease Elimination, Burnet Institute, Melbourne, Victoria, Australia.

Viral hepatitis affects more than 320 million people globally, leading to significant morbidity and mortality due to liver failure and hepatocellular carcinoma (HCC). More than 248 million people (3.2% globally) are chronically infected with hepatitis B virus (HBV), and an estimated 80 million people (1.1% globally) are chronically infected with hepatitis C virus (HCV). In 2015, more than 700 000 deaths were directly attributable to HBV, and nearly 500 000 deaths were attributable to HCV infection; 2-5% of HBV-infected people develop HCC per annum irrespective of the presence of cirrhosis, whereas 1-5% HCV-infected people with advanced fibrosis develop HCC per annum. The rapidly escalating global mortality related to HBV and HCV related viral hepatitis to be the 7th leading cause of death worldwide in 2013, from 10th leading cause in 1990. Australia, New Zealand, and Pacific Island Countries and Territories fall within the World Health Organization Western Pacific Region, which has a high prevalence of viral hepatitis and related morbidity, particularly HBV. Remarkably, in this region, HBV-related mortality is greater than for tuberculosis, HIV infection, and malaria combined. The region provides a unique contrast in viral hepatitis prevalence, health system resources, and approaches taken to achieve World Health Organization global elimination targets for HBV and HCV infection. This review highlights the latest evidence in viral hepatitis epidemiology and explores the health resources available to combat viral hepatitis, focusing on the major challenges and critical needs to achieve elimination in Australia, New Zealand, and Pacific Island Countries and Territories.
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http://dx.doi.org/10.1111/jgh.14457DOI Listing
January 2019

Traumatic Brain Injury and Firearm Use and Risk of Progressive Supranuclear Palsy Among Veterans.

Front Neurol 2018 20;9:474. Epub 2018 Jun 20.

Department of Neurosciences, University of California, San Diego, La Jolla, CA, United States.

Progressive supranuclear palsy (PSP) is a tauopathy that has a multifactorial etiology. Numerous studies that have investigated lead exposure and traumatic brain injury (TBI) as risk factors for other tauopathies, such as Alzheimer's disease, but not for PSP. We sought to investigate the role of firearm usage, as a possible indicator of lead exposure, and TBI as risk factors for PSP in a population of military veterans. We included participants from a larger case-control study who reported previous military service. Our sample included 67 PSP cases and 68 controls. Participants were administered a questionnaire to characterize firearm use in the military and occurrence of TBI. Cases were significantly less educated than controls. In unadjusted analyses, the proportion of PSP cases (80.6%) and controls (64.7%) who reported use of firearms as part of their military job was positively associated with PSP, odds ratio (OR) 2.2 (95% CI: 1-5.0). There were no significant case-control differences in mean service duration. There was only a weak association with history of TBI, OR 1.6 (95% CI: 0.8-3.4). In multivariate models, firearm usage (OR 3.7, 95% CI: 1.5, 9.8) remained significantly associated with PSP. Our findings show a positive association between firearm usage and PSP and an inverse association between education and PSP. The former suggests a possible etiologic role of lead. Further studies are needed to confirm the potential etiologic effects of metals on PSP. The study was registered in clinicaltrials.gov. ClinicalTrials.gov Identifier: NCT00431301.
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http://dx.doi.org/10.3389/fneur.2018.00474DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6020251PMC
June 2018

Methylene blue fluorescence of the ureter during colorectal surgery.

Surg Endosc 2018 09 21;32(9):4036-4043. Epub 2018 May 21.

Nuffield Department of Surgery, University of Oxford, Oxford, UK.

Background: Iatrogenic ureteric injury is a serious complication of colorectal surgery. Incidence is estimated to be between 0.3 and 1.5%. Of all ureteric injuries, 9% occur during colorectal procedures. Ureteric stents are utilised as a method to reduce the risk of injury; however, these are not without risk and do not guarantee prevention of injury. Fluorescence is a safe and effective alternative for intraoperative ureteric localisation. This proof of principle study aims to assess the use of methylene blue to fluoresce the ureter during colorectal surgery.

Method: Patients undergoing elective colorectal surgery were included in this open label, non-randomised study. Methylene blue was administered intravenously at varying doses (0.25-1 mg/kg) over 5 min, 10-15 min prior to entering 'ureteric territory.' Fluorescence was assessed using the PINPOINT Deep Red laparoscopic system at fixed time points by the surgeon and an independent observer.

Results: 42 patients received methylene blue; 2 patients were excluded from analysis. Of the 69 ureters assessed, 64 were seen under fluorescence. Of these, 14 were not visible under white light. 50 ureters were observed with both fluorescence and white light with 14 of these being seen earlier with fluorescence. In ten cases, fluorescence revealed the ureter to be in a different location than suspected.

Conclusion: Fluorescence is a promising method to allow visualisation of the ureter, where it is not identified easily under standard operative conditions, thereby improving safety and reducing operative time and difficulty.
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http://dx.doi.org/10.1007/s00464-018-6219-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6096537PMC
September 2018

Health and wellbeing of Indigenous adolescents in Australia.

Authors:
Chris Cunningham

Lancet 2018 02;391(10122):720-721

Research Centre for Maori Health and Development, Massey University, PO Box 756, Wellington 6021, New Zealand. Electronic address:

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http://dx.doi.org/10.1016/S0140-6736(18)30470-7DOI Listing
February 2018

Outcomes following completion and salvage surgery for early rectal cancer: A systematic review.

Eur J Surg Oncol 2018 01 14;44(1):15-23. Epub 2017 Nov 14.

Department of Colorectal Surgery, Oxford University Hospitals, United Kingdom.

Objectives: To establish outcomes after completion and salvage surgery following local excision in literature published since 2005, to inform decision-making when offering local excision.

Background: Local excision of early rectal cancer aims to offer cure while maintaining quality of life through organ preservation. However, some patients will require radical surgery, prompted by unexpected poor pathology or local recurrence. Consistent definition and reporting of these scenarios is poor. We propose the term "salvage surgery" for recurrence after local excision and "completion surgery" for poor pathology.

Methods: Electronic databases were searched in February 2016. Studies since 2005 describing outcomes for radical surgery following local excision of rectal cancer were included. Pooled and average values were obtained.

Results: A total of 23 studies included 262 completion and 165 salvage operations. Most completion operations were done within 4 weeks; local recurrence rate was 5% and overall disease recurrence rate was 14%. The majority of salvage operations for local recurrence were within 15 months of local excision, often following adjuvant treatment. Re-do local excision was used in 15%; APR was the most common radical procedure. Further local recurrence was uncommon (3%) but overall disease recurrence rate was 13%. Estimated 5-year survival was in the order of 50%. Heterogeneity was high among the studies.

Conclusions: Patients undergoing local excision must be informed of risks and expected outcomes, but better data on completion and salvage surgery are required to achieve this.

Systematic Review Registration Number: CRD42014014758.
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http://dx.doi.org/10.1016/j.ejso.2017.10.212DOI Listing
January 2018