DTI of Opioid-Exposed Fetuses Using ComBat Harmonization: A Bi-Institutional Study.

BACKGROUND AND PURPOSE: The underlying mechanisms leading to altered cognitive, behavioral, and vision outcomes in children with prenatal opioid exposure are yet to be fully understood. Some studies suggest WM alterations in infants and children with prenatal opioid exposure; however, the time course of WM changes is unknown. We aimed to evaluate differences in diffusion tensor imaging MRI parameters in the brain between opioid exposed fetuses and normal controls. MATERIALS AND METHODS: This is a pilot, prospective cohort study in which subjects in the third trimester of pregnancy underwent fetal DTI of the brain with 20 noncolinear diffusion directions and a b-value of 500 s/mm2 at 2.5-mm isotropic resolution. RESULTS: The study included a total of 26 fetuses, 11 opioid-exposed (mean gestational age, 32.61 [SD, 2.35] weeks) and 15 unexposed controls (mean gestational age, 31.77 [SD, 1.68] weeks). After we adjusted for gestational age, fractional anisotropy values were significantly higher in opioid-exposed fetuses relative to controls in 8 WM tracts: the bilateral lemniscus (left: P = .017; right: P = .020), middle cerebellar peduncle (P = .027), left inferior cerebellar peduncle (P = .026), right sagittal stratum (P = .040), right fornix stria terminalis (P = .022), right inferior fronto-occipital fasciculus (P = .011), and the right uncinate fasciculus (P = .033). Significant alteration was also identified in other DTI indices involving a series of brain regions. CONCLUSIONS: Our data demonstrate initial evidence of cerebral WM microstructural differences between opioid-exposed fetuses and unexposed controls. Further studies in larger patient populations will be needed to fully understand these findings.

Preoperative intravenous iron therapy and survival after colorectal cancer surgery: long-term results from the IVICA randomised controlled trial.

AIM: Preoperative iron is frequently used for the correction of anaemia in colorectal cancer surgery. However, enteral iron intake may promote tumour growth and progression which could influence cancer recurrence and patient survival. We explore the long-term outcomes of patients receiving either oral or intravenous iron replacement therapy as part of a previous randomized controlled trial. METHODS: The IVICA trial randomized anaemic colorectal cancer patients to receive either oral (OI, control) or intravenous (IVI, treatment) iron prior to their elective operation. Follow-up analysis of all patients recruited to this multicentre trial who underwent surgical resection with curative intent was performed. Kaplan-Meier survival estimates and Cox proportional hazard models were used to compare groups. A pooled group multivariable analysis comparing patients who achieved resolution of anaemia preoperatively to those who did not was also undertaken. RESULTS: In all, 110 of the 116 patients previously enrolled were eligible for analysis (OI n = 56, IVI n = 54). Median overall follow-up duration was 61 months (interquartile range 46-67). No significant difference in 5-year overall survival (hazard ratio (HR) 1.22, 95% CI 0.65-2.28, P = 0.522) or disease-free survival (HR 1.08, 95% CI 0.61-1.92, P = 0.79) was observed between OI and IVI. A pooled analysis of treatment groups found that preoperative resolution of anaemia led to improved 5-year overall survival on multivariable analysis (HR 3.38, 95% CI 1.07-11.56, P = 0.044). CONCLUSION: We recommend IVI for the preoperative correction of anaemia. Route of iron therapy did not significantly influence survival. Preoperative anaemia correction may lead to an overall survival advantage following elective colorectal cancer surgery.

The impact of pre-operative intravenous iron on quality of life after colorectal cancer surgery: outcomes from the intravenous iron in colorectal cancer-associated anaemia (IVICA) trial.

Anaemia is associated with a reduction in quality of life, and is common in patients with colorectal cancer . We recently reported the findings of the intravenous iron in colorectal cancer-associated anaemia (IVICA) trial comparing haemoglobin levels and transfusion requirements following intravenous or oral iron replacement in anaemic colorectal cancer patients undergoing elective surgery. In this follow-up study, we compared the efficacy of intravenous and oral iron at improving quality of life in this patient group. We conducted a multicentre, open-label randomised controlled trial. Anaemic colorectal cancer patients were randomly allocated at least two weeks pre-operatively, to receive either oral (ferrous sulphate) or intravenous (ferric carboxymaltose) iron. We assessed haemoglobin and quality of life scores at recruitment, immediately before surgery and at outpatient review approximately three months postoperatively, using the Short Form 36, EuroQoL 5-dimension 5-level and Functional Assessment of Cancer Therapy - Anaemia questionnaires. We recruited 116 anaemic patients across seven UK centres (oral iron n = 61 (53%), and intravenous iron n = 55 (47%)). Eleven quality of life components increased by a clinically significant margin in the intravenous iron group between recruitment and surgery compared with one component for oral iron. Median (IQR [range]) visual analogue scores were significantly higher with intravenous iron at a three month outpatient review (oral iron 70, (60-85 [20-95]); intravenous iron 90 (80-90 [50-100]), p = 0.001). The Functional Assessment of Cancer Therapy - Anaemia score comprises of subscales related to cancer, fatigue and non-fatigue items relevant to anaemia. Median outpatient scores were higher, and hence favourable, for intravenous iron on the Functional Assessment of Cancer Therapy - Anaemia subscale (oral iron 66 (55-72 [23-80]); intravenous iron 71 (66-77 [46-80]); p = 0.002), Functional Assessment of Cancer Therapy - Anaemia trial outcome index (oral iron 108 (90-123 [35-135]); intravenous iron 121 (113-124 [81-135]); p = 0.003) and Functional Assessment of Cancer Therapy - Anaemia total score (oral iron 151 (132-170 [69-183]); intravenous iron 168 (160-174 [125-186]); p = 0.005). These findings indicate that intravenous iron is more efficacious at improving quality of life scores than oral iron in anaemic colorectal cancer patients.

The Association of Coloproctology of Great Britain and Ireland consensus guidelines in surgery for inflammatory bowel disease.

AIM: There is a requirement of an expansive and up to date review of surgical management of inflammatory bowel disease (IBD) that can dovetail with the medical guidelines produced by the British Society of Gastroenterology. METHODS: Surgeons who are members of the ACPGBI with a recognised interest in IBD were invited to contribute various sections of the guidelines. They were directed to produce a procedure based document using literature searches that were systematic, comprehensible, transparent and reproducible. Levels of evidence were graded. An editorial board was convened to ensure consistency of style, presentation and quality. Each author was asked to provide a set of recommendations which were evidence based and unambiguous. These recommendations were submitted to the whole guideline group and scored. They were then refined and submitted to a second vote. Only those that achieved >80% consensus at level 5 (strongly agree) or level 4 (agree) after 2 votes were included in the guidelines. RESULTS: All aspects of surgical care for IBD have been included along with 157 recommendations for management. CONCLUSION: These guidelines provide an up to date and evidence based summary of the current surgical knowledge in the management of IBD and will serve as a useful practical text for clinicians performing this type of surgery.

Closure of the perineal defect after abdominoperineal excision for rectal adenocarcinoma - ACPGBI Position Statement.

BACKGROUND: Perineal wound morbidity is common following abdominoperineal excision of the rectum (APE). There is no consensus on the optimum perineal reconstruction method after APE, and in particular 'extra-levator APE' (ELAPE). METHODS: A systematic review of the PubMed, Embase and Cochrane databases was performed. This position statement formulated clinical questions and graded the evidence to make recommendations. RESULTS: Perineal wound complications may be higher following ELAPE compared to 'conventional APE (cAPE)' however there is insufficient evidence to recommend cAPE over ELAPE with regards to the impact upon perineal wound healing. The majority of cAPE studies have used primary closure with varying complication rates reported. Where concerns regarding perineal wound healing exist, myocutaneous flap closure may be considered as an alternative method. There is minimal available evidence on perineal mesh reconstruction following cAPE. Primary closure, mesh use and myocutaneous flap reconstruction following ELAPE has been reported although variations in definitions and low-quality of available evidence limit comparison. There is insufficient evidence to recommend one particular method of perineal closure after ELAPE. Primary perineal closure is likely to have a higher risk of perineal herniation. Myocutaneous flaps and biological mesh have been effectively used in ELAPE closure. There is insufficient evidence to support one particular type of flap or mesh. Perineal wound complication rates are significantly increased when neo-adjuvant radiotherapy is delivered, regardless of surgical technique. There is no evidence that laparoscopy reduces APE perineal wound complications. CONCLUSION: This position statement updates clinicians on current evidence around perineal closure after APE surgery.

An international consensus statement on the management of postoperative anaemia after major surgical procedures.

Despite numerous guidelines on the management of anaemia in surgical patients, there is no pragmatic guidance for the diagnosis and management of anaemia and iron deficiency in the postoperative period. A number of experienced researchers and clinicians took part in a two-day expert workshop and developed the following consensus statement. After presentation of our own research data and local policies and procedures, appropriate relevant literature was reviewed and discussed. We developed a series of best-practice and evidence-based statements to advise on patient care with respect to anaemia and iron deficiency in the postoperative period. These statements include: a diagnostic approach to iron deficiency and anaemia in surgical patients; identification of patients appropriate for treatment; and advice on practical management and follow-up that is easy to implement. Available data allow the fulfilment of the requirements of Pillar 1 of Patient Blood Management. We urge national and international research funding bodies to take note of these recommendations, particularly in terms of funding large-scale prospective, randomised clinical trials that can most effectively address the important clinical questions and this clearly unmet medical need.

Review of current practice and outcomes following ileoanal pouch surgery: lessons learned from the Ileoanal Pouch Registry and the 2017 Ileoanal Pouch Report.

AIM: The second Association of Coloproctology of Great Britain and Ireland (ACPGBI) Ileoanal Pouch Registry (IPR) report was released in July 2017 following a first report in 2012. This article provides a summary of data derived from the most recent IPR report (2017 Ileoanal Pouch Report. https://www.acpgbi.org.uk/content/uploads/2016/07/Ileoanal-Pouch-Report-2017-FINAL.compressed.pdf). METHOD: The IPR is an electronic database of voluntarily submitted data including patient demographics, disease, intra-operative and postoperative factors submitted by consultant surgeons or delegates. Data up to 31 March 2017 have been analysed for this report. RESULTS: A total of 5352 pouch operations were carried out at 76 UK and four European centres by 154 surgeons over four decades. Recorded procedures have increased over time but data submission is voluntary and underestimates actual volume. Significant variation exists in institutional volume; 73 centres entered data on patients undergoing pouch surgery during the past 5 years. Of these, 44 centres have submitted ≤ 10 cases, with 10 centres submitting one patient and nine centres two cases. Since 2013, minimal access surgery has been employed in 54% of cases. Rectal dissection was undertaken in the total mesorectal excision plane in 69%. J-pouch configuration was used in 99% of cases and 90% of pouch-anal anastomoses were performed using a stapled technique. Including all years, the IPR rate of pelvic sepsis was 9.4% and the rate of pouch failure was 4.7%. CONCLUSION: The IPR holds the largest voluntary repository of data on ileoanal pouch surgery. The second report from the IPR records marked refinements in surgical technique over time but also highlights wide variation in institutional caseload and outcome across the UK.

The colorectal surgeon's personality may influence the rectal anastomotic decision.

AIM: Colorectal surgeons regularly make the decision to anastomose, defunction or form an end colostomy when performing rectal surgery. This study aimed to define personality traits of colorectal surgeons and explore any influence of such traits on the decision to perform a rectal anastomosis. METHOD: Fifty attendees of The Association of Coloproctology of Great Britain and Ireland 2016 Conference participated. After written consent, all underwent personality testing: alexithymia (inability to understand emotions), type of thinking process (intuitive versus rational) and personality traits (extraversion, agreeableness, openness, emotional stability, conscientiousness). Questions were answered regarding anastomotic decisions in various clinical scenarios and results analysed to reveal any influence of the surgeon's personality on anastomotic decision. RESULTS: Participants were: male (86%), consultants (84%) and based in England (68%). Alexithymia was low (4%) with 81% displaying intuitive thinking (reflex, fast). Participants scored higher in emotional stability (ability to remain calm) and conscientiousness (organized, methodical) compared with population norms. Personality traits influenced the next anastomotic decision if: surgeons had recently received criticism at a departmental audit meeting; were operating with an anaesthetist that was not their regular one; or there had been no anastomotic leaks in their patients for over 1 year. CONCLUSION: Colorectal surgeons have speciality relevant personalities that potentially influence the important decision to anastomose and could explain the variation in surgical practice across the UK. Future work should explore these findings in other countries and any link of personality traits to patient-related outcomes.

Anaemia as a risk stratification tool for symptomatic patients referred via the two-week wait pathway for colorectal cancer.

Introduction Anaemia is associated with cancer. In 2014 a new form was introduced in our department requesting a haemoglobin (Hb) result on every two-week wait referral for suspected colorectal cancer (CRC). The aim of this study was to review the impact of this intervention. In particular, the significance of any evidence of anaemia (without additional indices) was investigated. Methods A review was conducted of 1,500 consecutive suspected CRC referrals recorded prospectively over a 10-month period. Data on demographics, referral Hb, referral criteria and outcomes were analysed. Anaemia was defined according to World Health Organization criteria (Hb <120g/l for women, Hb <130g/l for men). Results Overall, 1,015 patients were eligible for inclusion in the study. Over a third (38.2%) were documented as anaemic on referral. These patients were three times more likely to be diagnosed with CRC than non-anaemic patients (odds ratio [OR]: 3.22, 95% confidence interval [CI]: 1.87-5.57). Using a more stringent threshold (Hb <100g/l for women and <110g/l for men), they were four times more likely to have CRC (OR: 4.27, 95% CI: 2.35-7.75). Almost a quarter (23.7%) were actually anaemic at the time of referral but not referred with anaemia. In this subgroup, there was a 2.8-fold increase in risk of CRC diagnosis compared with non-anaemic patients (adjusted OR: 2.77, 95% CI: 1.55-4.95). Conclusions Nearly a quarter of patients not referred with iron deficiency anaemia had evidence of anaemia and this was still associated with a higher rate of CRC detection. A full blood count alone might help to risk stratify symptoms such as change in bowel habit in patients on urgent pathways and identify those cases most likely to benefit from invasive investigation.

Variation in practice of pouch surgery in England - using SWORD data to cut to the chase and justify centralization.

AIM: Increasing scrutiny on both individual and unit outcomes after surgical procedures is now expected. In the field of inflammatory bowel disease, this is particularly pertinent for outcomes after ileoanal pouch surgery. METHOD: The Surgical Workload and Outcomes Research Database (SWORD) relies on administrative data derived from Hospital Episode Statistics collected in England. The platform was interrogated for pouch procedures undertaken in England between April 2009 and December 2016 to assess national caseload and, between April 2012 and December 2016, to assess variation in caseload and outcomes after pouch surgery. RESULTS: In England there is a suggestion that numbers of pouch procedures may be decreasing. Over 80% of Trusts offering pouch surgery do so at very low volume with less than five procedures per year. There is also a clear phenomenon of the occasional pouch surgeon with 126 surgeons undertaking just one pouch operation during the study period of almost 5 years. Laparoscopic practice varies but 60% of pouches overall were done via an open approach. Mean length of stay was 10.1 days and average 30-day readmission rates were 27.4%. Outside London there appears to be an increasing trend for higher volume units to do more adult pouch procedures and lower volume units to do fewer. CONCLUSION: Low volume units and occasional pouch surgeons present a strong argument for centralization of pouch surgery. Data from England outside London suggest that this may already be happening.

Current management of small bowel obstruction in the UK: results from the National Audit of Small Bowel Obstruction clinical practice survey.

AIM: Small bowel obstruction (SBO) is associated with high rates of morbidity and mortality. The National Audit of Small Bowel Obstruction (NASBO) is a collaboration between trainees and specialty associations to improve the care of patients with SBO through national clinical audit. The aim of this study was to define current consultant practice preferences in the management of SBO in the UK. METHOD: A survey was designed to assess practice preferences of consultant surgeons. The anonymous survey captured demographics, indications for surgery or conservative management, use of investigations including water-soluble contrast agents (WSCA), use of laparoscopy and nutritional support strategies. The questionnaire underwent two pilot rounds prior to dissemination via the NASBO network. RESULTS: A total of 384 responses were received from 131 NASBO participating units (overall response rate 29.2%). Abdominal CT and serum urea and electrolytes were considered essential initial investigations by more than 80% of consultants. Consensus was demonstrated on indications for early surgery and conservative management. Three hundred and thirty-eight (88%) respondents would consider use of WSCA; of these, 328 (97.1%) would use it in adhesive SBO. Two hundred (52.1%) consultants considered a laparoscopic approach when operating for SBO. Oral nutritional supplements were favoured in operatively managed patients by 259 (67.4%) respondents compared with conservatively managed patients (186 respondents, 48.4%). CONCLUSION: This survey demonstrates consensus on imaging requirements and indications for early surgery in the management of SBO. Significant variation exists around awareness of the need for nutritional support in patients with SBO, and on strategies to achieve this support.

The effect of acetazolamide on intra-ocular pressure after Trendelenburg positioning - a randomised double-blind crossover trial in volunteers.

Recent evidence suggests Trendelenburg positioning can produce a significant rise in intra-ocular pressure. Peri-operative vision loss in patients undergoing laparoscopic colorectal surgery has been reported with the rise in intra-ocular pressure suggested as a possible factor. Acetazolamide decreases intra-ocular pressure by reducing the formation of aqueous humour, so we aimed to investigate if it could attenuate the intra-ocular pressure rise that can occur in the Trendelenburg position. Nine healthy volunteers were recruited and randomly assigned to a double-blind crossover comparison of placebo or acetazolamide with a minimal 4 days' washout period before the second study day. One and a half hours after taking the medication, volunteers lay head-down at 17° for 4 h. Intraocular pressure measurements were repeated in both eyes every 30 min over a 4-h period. There were two males and seven female volunteers, with a mean (SD) age of 54.3 (18.5) years. The mean (SD) increase in intra-ocular pressure following 4 h in the Trendelenburg position was 3.17 (4.63) mmHg after the placebo, and 0.02 (4.01) mmHg (p = 0.02) after acetazolamide. We have shown than acetazolamide can attenuate the rise that occurs in intra-ocular pressure when in the Trendelenburg position.

Randomized clinical trial of preoperative oral versus intravenous iron in anaemic patients with colorectal cancer.

BACKGROUND: Treatment of preoperative anaemia is recommended as part of patient blood management, aiming to minimize perioperative allogeneic red blood cell transfusion. No clear evidence exists outlining which treatment modality should be used in patients with colorectal cancer. The study aimed to compare the efficacy of preoperative intravenous and oral iron in reducing blood transfusion use in anaemic patients undergoing elective colorectal cancer surgery. METHODS: Anaemic patients with non-metastatic colorectal adenocarcinoma were recruited at least 2 weeks before surgery and randomized to receive oral (ferrous sulphate) or intravenous (ferric carboxymaltose) iron. Perioperative changes in haemoglobin, ferritin, transferrin saturation and blood transfusion use were recorded until postoperative outpatient review. RESULTS: Some 116 patients were included in the study. There was no difference in blood transfusion use from recruitment to trial completion in terms of either volume of blood administered (P = 0·841) or number of patients transfused (P = 0·470). Despite this, increases in haemoglobin after treatment were higher with intravenous iron (median 1·55 (i.q.r. 0·93-2·58) versus 0·50 (-0·13 to 1·33) g/dl; P < 0·001), which was associated with fewer anaemic patients at the time of surgery (75 versus 90 per cent; P = 0·048). Haemoglobin levels were thus higher at surgery after treatment with intravenous than with oral iron (mean 11·9 (95 per cent c.i. 11·5 to 12·3) versus 11·0 (10·6 to 11·4) g/dl respectively; P = 0·002), as were ferritin (P < 0·001) and transferrin saturation (P < 0·001) levels. CONCLUSION: Intravenous iron did not reduce the blood transfusion requirement but was more effective than oral iron at treating preoperative anaemia and iron deficiency in patients undergoing colorectal cancer surgery.

International consensus statement on the peri-operative management of anaemia and iron deficiency.

Despite current recommendations on the management of pre-operative anaemia, there is no pragmatic guidance for the diagnosis and management of anaemia and iron deficiency in surgical patients. A number of experienced researchers and clinicians took part in an expert workshop and developed the following consensus statement. After presentation of our own research data and local policies and procedures, appropriate relevant literature was reviewed and discussed. We developed a series of best-practice and evidence-based statements to advise on patient care with respect to anaemia and iron deficiency in the peri-operative period. These statements include: a diagnostic approach for anaemia and iron deficiency in surgical patients; identification of patients appropriate for treatment; and advice on practical management and follow-up. We urge anaesthetists and peri-operative physicians to embrace these recommendations, and hospital administrators to enable implementation of these concepts by allocating adequate resources.

Colorectal cancer outcomes in patients aged over 85 years.

INTRODUCTION: The prevalence of colorectal cancer is increasing in the elderly. We examined the treatment and outcomes in our institution of patients aged over 85 years with proven colorectal adenocarcinoma. METHODS: One hundred and five patients were identified and stratified by treatment received: curative surgery (CS), other treatments (OT) or best supportive care (BSC). Data on demographics, staging, treatment and survival was collected and analysed. RESULTS: Forty two patients received CS, 36 OT and 27 BSC. While the treated groups (CS and OT) were similar in terms of age (p=0.35) and staging (p=0.16), BSC patients were significantly older and had higher stage disease (p<0.01). Survival was significantly poorer among BSC patients, at a mean of 9.7 months (95% confidence interval [CI] 4.7-14.7) versus 41.6 months (95% CI 32.5-50.7) and OT 27.3 months (95% CI 20.4-34.1) for the CS and OT groups (p<0.001). There was no significant survival difference between CS and OT groups within 2 years of treatment (p=0.12). Thereafter, OT patients had a very similar 5-year survival to that of the BSC group, at 13% versus 43% in CS patients (p<0.001). CONCLUSIONS: These data suggest that, up to 2 years following treatment, the risks of resectional surgery for colorectal cancer may neutralise any benefit. However, those that survive beyond this period show improvements. The challenge of improving patient selection is most acute in the growing ageing population, and highlights the current focus on presenting all treatment options to 'a reasonable patient'.