Developing a curriculum for advanced fellowship training in complex cancer for the UK.

AIM: Surgery for complex colorectal cancer is elaborate: preoperative assessment, patient selection, radiological interpretation, operative strategy, operative technical skills, operative standardization, postoperative care and management of complications are all critical components. Given this complexity, training that encompasses all these crucial aspects to generate suitably edified surgeons is essential. To date, no curriculum exists to guide training in advanced and recurrent pelvic malignancy, particularly for complex colorectal cancer. Such a curriculum would potentially offer numerous advantages, not only for individual surgeons but also for research, governance, international collaboration and benchmarking. The aim of this study was to design and develop a framework for a curriculum for fellowship training in complex colorectal cancer that encompasses pelvic exenteration surgery. METHOD: Kern described a six-step method for curriculum design that is now widely adopted in medical education. Our study utilizes steps 1-4 of Kern's method to develop a syllabus and assessment framework for curriculum development for fellowship training in complex colorectal cancer encompassing pelvic exenteration. A literature review was conducted to address step 1, followed by targeted needs assessment in step 2 by conducting focus groups with trainees, fellows and experts to identify learning needs and goals with objective setting for step 3. An expert consensus group then voted on these recommendations and developed educational strategy recommendations as step 4. For the purposes of brevity, 'pelvic exenteration' in the text is taken to also encompass extended and multivisceral resections that fall under the remit of complex [colorectal] cancer. RESULTS: Step 1 of Kern's method identified a gap in the literature on curricula in complex cancer surgery. Step 2 identified key areas regarded as learning needs by trainees, including anatomy, hands-on experience and case volume. Step 3 defined the goals and objectives of a fellowship curriculum, defined in six domains including theoretical knowledge, decision-making, technical skills, postoperative management and continuing professional development. Finally, as a prelude to stages 5 and 6, a strategy for implementation and for feedback and assessment was agreed by an expert consensus meeting that defined case volume (a minimum of 20 pelvic exenteration operations within a fellowship period) and coverage of this syllabus with derived metrics. CONCLUSIONS: Our working group has developed a curriculum framework for advanced fellowship training in complex cancer in the UK. Validation is needed through implementation, and affirmation of its utility, both nationally and internationally, must be sought.

ASPIRE for excellence in curriculum development.

The objective of the ASPIRE award programme of the International Association for Health Professions Education is to go beyond traditional accreditation processes. Working in partnership with the ASPIRE Academy, the programme aims to encourage and support excellence in health professions education, in part by showcasing and exemplifying best practices. Each year ASPIRE award applications received from institutions across the globe describe their greatest achievements in a variety of areas, one of which is curriculum development, where evaluation of applications is carried out using a framework of six domains. These are described in this paper as key elements of excellence, specifically, Organisational Structure and Curriculum Management; Underlying Educational Strategy; Content Specification and Pedagogy; Teaching and Learning Methods and Environment; Assessment, Monitoring and Evaluation; Scholarship. Using examples from the content of submissions of three medical schools from very different settings that have been successful in the past few years, achievements in education processes and outcomes of institutions around the world are highlighted in ways that are relevant to their local and societal contexts.

A SARS-CoV-2 outbreak associated with five air force bases and a nightclub following the lifting of COVID-19-related social restrictions, United Kingdom, July-to-September 2021.

We describe the management of two linked severe acute respiratory coronavirus 2 (SARS-CoV-2) outbreaks, predominantly amongst 18-35-year-olds, in a UK county in July-to-September 2021, following the lifting of national coronavirus disease 2019 (COVID-19)-associated social restrictions. One was associated with a nightclub and one with five air force bases. On week beginning 2nd August 2021, air force contact tracing teams detected 68 cases across five bases within one county; 21 (30.9%) were associated with a night-time economy venue, 13 (19.1%) with night-time economy venues in the county's main town and at least one case per base (n = 6, 8.8%) with a particular nightclub in this town, which itself had been associated with 302 cases in the previous week (coinciding with its reopening following a national lockdown). In response, Public Health England/United Kingdom Health Security Agency, air force and local authority teams collaboratively implemented communication strategies and enhanced access to SARS-CoV-2 testing and vaccination. Key challenges included attempting to encourage behaviours that reduce likelihood of transmission to a population who may have considered themselves at low risk from severe COVID-19. This report may inform future preparation for, and management of, easing of potential future pandemic-related social restrictions, and how an outbreak in this context may be addressed.

Patient and multidisciplinary team perspectives on watch and wait in rectal cancer.

This article adopts a multidisciplinary approach, including surgery, oncology, radiology and patient perspectives, to discuss the key points of debate surrounding a watch and wait approach. In an era of shared decision-making, discussion of watch and wait as an option in the context of complete clinical response is appropriate, although it is not the gold standard treatment. Key challenges are the difficulty in assessing for a complete clinical response, prediction of recurrence and access to timely diagnostics for surveillance. Salvage surgery has good results if regrowth is detected early but does have imperfect outcomes, with only a 90% salvage rate. Good communication with patients about the risks and alternatives is essential. Patients undergoing watch and wait should ideally be enrolled in prospective registries or clinical trials.

Pancreaticoduodenectomy with right hemicolectomy for advanced malignancy: a single UK hepatopancreaticobiliary centre experience.

AIM: Locally advanced intestinal neoplasms including colon cancer may require radical en bloc pancreaticoduodenectomy and right hemicolectomy (PD-RC) to achieve curative, margin-negative resection, but the safety and benefit of this uncommon procedure has not been established. The Association of Coloproctology of Great Britain and Ireland IMPACT initiative has also highlighted a lack of awareness about current services available within the UK for patients with advanced colorectal cancer and concerns about low-volume centres managing complex cases. Thus, we aimed to review the feasibility, safety and long-term outcomes of this procedure at a single high-volume hepatopancreaticobiliary surgery unit in the UK. METHOD: A retrospective cohort study was performed using a database of all consecutive patients with intestinal cancer who had been referred to our regional advanced multidisciplinary team and undergone PD-RC in a 7-year period (2013-2020). Clinico-pathological and outcome data were reviewed. RESULTS: Ten patients (mean age 54 ± 13, 8/10 men) were identified. Final histology revealed the primary tumour sites were colon (n = 7) and duodenum (n = 3). R0 resection was achieved in all cases. The major complication rate (Clavien-Dindo ≥ 3) was 10% (1/10) with no deaths within 90 days of surgery. The Kaplan-Meier estimated 5-year overall survival was 83.3% (95% CI 58.3%-100%). Univariate survival analysis identified perineural invasion and extra-colonic origin as predictors of poor survival (log-rank P < 0.05). CONCLUSION: En bloc PD-RC for locally advanced intestinal cancer can be performed safely with a high proportion of margin-negative resections and resultant long-term survival in carefully selected patients.

Protective ileostomy creation after anterior resection of the rectum: Shared decision-making or still subjective?

AIM: The choice of whether to perform protective ileostomy (PI) after anterior resection (AR) is mainly guided by risk factors (RFs) responsible for the development of anastomotic leakage (AL). However, clear guidelines about PI creation are still lacking in the literature and this is often decided according to the surgeon's preferences, experiences or feelings. This qualitative study aims to investigate, by an open-ended question survey, the individual surgeon's decision-making process regarding PI creation after elective AR. METHOD: Fifty four colorectal surgeons took part in an electronic survey to answer the questions and describe what usually led their decision to perform PI. A content analysis was used to code the answers. To classify answers, five dichotomous categories (In favour/Against PI, Listed/Unlisted RFs, Typical/Atypical, Emotions/Non-emotions, Personal experience/No personal experience) have been developed. RESULTS: Overall, 76% of surgeons were in favour of PI creation and 88% considered listed RFs in the question of whether to perform PI. Atypical answers were reported in 10% of cases. Emotions and personal experience influenced surgeons' decision-making process in 22% and 49% of cases, respectively. The most frequently considered RFs were the distance of the anastomosis from the anal verge (96%), neoadjuvant chemoradiotherapy (88%), a positive intraoperative leak test (65%), blood loss (37%) and immunosuppression therapy (35%). CONCLUSION: The indications to perform PI following rectal cancer surgery lack standardization and evidence-based guidelines are required to inform practice. Until then, expert opinion can be helpful to assist the decision-making process in patients who have undergone AR for adenocarcinoma.

Assessment of the 2020 NICE criteria for preoperative radiotherapy in patients with rectal cancer treated by surgery alone in comparison with proven MRI prognostic factors: a retrospective cohort study.

BACKGROUND: Selection of patients for preoperative treatment in rectal cancer is controversial. The new 2020 National Institute for Health and Care Excellence (NICE) guidelines, consistent with the National Comprehensive Cancer Network guidelines, recommend preoperative radiotherapy for all patients except for those with radiologically staged T1-T2, N0 tumours. We aimed to assess outcomes in non-irradiated patients with rectal cancer and to stratify results on the basis of NICE criteria, compared with known MRI prognostic factors now omitted by NICE. METHODS: For this retrospective cohort study, we identified patients undergoing primary resectional surgery for rectal cancer, without preoperative radiotherapy, at Basingstoke Hospital (Basingstoke, UK) between Jan 1, 2011, and Dec 31, 2016, and at St Marks Hospital (London, UK) between Jan 1, 2007, and Dec 31, 2017. Patients with MRI-detected extramural venous invasion, MRI-detected tumour deposits, and MRI-detected circumferential resection margin involvement were categorised as MRI high-risk for recurrence (local or distant), and their outcomes (disease-free survival, overall survival, and recurrence) were compared with patients defined as high-risk according to NICE criteria (MRI-detected T3+ or MRI-detected N+ status). Kaplan-Meier and Cox proportional hazards analyses were used to compare the groups. FINDINGS: 378 patients were evaluated, with a median of 66 months (IQR 44-95) of follow up. 22 (6%) of 378 patients had local recurrence and 68 (18%) of 378 patients had distant recurrence. 248 (66%) of 378 were classified as high-risk according to NICE criteria, compared with 121 (32%) of 378 according to MRI criteria. On Kaplan-Meier analysis, NICE high-risk patients had poorer 5-year disease-free survival compared with NICE low-risk patients (76% [95% CI 70-81] vs 87% [80-92]; hazard ratio [HR] 1·91 [95% CI 1·20-3·03]; p=0·0051) but not 5-year overall survival (80% [74-84] vs 88% [81-92]; 1·55 [0·94-2·53]; p=0·077). MRI criteria separated patients into high-risk versus low-risk groups that predicted 5-year disease-free survival (66% [95% CI 57-74] vs 88% [83-91]; HR 3·01 [95% CI 2·02-4·47]; p<0·0001) and 5-year overall survival (71% [62-78] vs 89% [84-92]; 2·59 [1·62-3·88]; p<0·0001). On multivariable analysis, NICE risk assessment was not associated with either disease-free survival or overall survival, whereas MRI criteria predicted disease-free survival (HR 2·74 [95% CI 1·80-4·17]; p<0·0001) and overall survival (HR 2·44 [95% CI 1·51-3·95]; p=0·00027). 139 NICE high-risk patients who were defined as low-risk based on MRI criteria had similar disease-free survival as 118 NICE low-risk patients; therefore, 37% (139 of 378) of patients in this study cohort would have been overtreated with NICE 2020 guidelines. Of the 130 patients defined as low-risk by NICE guidelines, 12 were defined as high-risk on MRI risk stratification and would have potentially been missed for treatment. INTERPRETATION: Compared to previous guidelines, implementation of the 2020 NICE guidelines will result in significantly more patients receiving preoperative radiotherapy. High-quality MRI selects patients with good outcomes (particularly low local recurrence) without radiotherapy, with little margin for improvement. Overuse of radiotherapy could occur with this unselective approach. The high-risk group, with the most chance of benefiting from preoperative radiotherapy, is not well selected on the basis of NICE 2020 criteria and is better identified with proven MRI prognostic factors (extramural venous invasion, tumour deposits, and circumferential resection margin). FUNDING: None.

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

OBJECTIVE: To examine the impact of The National Training Program for Lapco on the rate of laparoscopic surgery and clinical outcomes of cases performed by Lapco surgeons after completion of training. SUMMARY OF 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: One hundred eight Lapco delegates performed 4586 elective colo-rectal resections pre-Lapco and 5115 post-Lapco while non-Lapco surgeons performed 72,930 matched cases. Lapco delegates had a 37.8% increase in laparoscopic surgery which was greater than non-Lapco surgeons by 20.9% [95% confidence interval (CI), 18.5-23.3, 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.

Altered immunity to microbiota, B cell activation and depleted γδ/resident memory T cells in colorectal cancer.

The role of microbiota:immune system dysregulation in the etiology of colorectal cancer (CRC) is poorly understood. CRC develops in gut epithelium, accompanied by low level inflammatory signaling, intestinal microbial dysbiosis and immune dysfunction. We examined populations of intraepithelial lymphocytes in non-affected colonic mucosa of CRC and healthy donors and circulating immune memory to commensal bacterial species and yeasts. γδ T cells and resident memory T cells, populations with a regulatory CD39-expressing phenotype, were found at lower frequencies in the colonic tissue of CRC donors compared to healthy controls. Patterns of T cell proliferative responses to a panel of commensal bacteria were distinct in CRC, while B cell memory responses to several bacteria/yeast were significantly increased, accompanied by increased proportions of effector memory B cells, transitional B cells and plasmablasts in blood. IgA responses to mucosal microbes were unchanged. Our data describe a novel immune signature with similarities to and differences from that of inflammatory bowel disease. They implicate B cell dysregulation as a potential contributor to parainflammation and identify pathways of weakened barrier function and tumor surveillance in CRC-susceptible individuals.

Benchmarks in colorectal surgery: multinational study to define quality thresholds in high and low anterior resection.

BACKGROUND: Benchmark comparisons in surgery allow identification of gaps in the quality of care provided. The aim of this study was to determine quality thresholds for high (HAR) and low (LAR) anterior resections in colorectal cancer surgery by applying the concept of benchmarking. METHODS: This 5-year multinational retrospective study included patients who underwent anterior resection for cancer in 19 high-volume centres on five continents. Benchmarks were defined for 11 relevant postoperative variables at discharge, 3 months, and 6 months (for LAR). Benchmarks were calculated for two separate cohorts: patients without (ideal) and those with (non-ideal) outcome-relevant co-morbidities. Benchmark cut-offs were defined as the 75th percentile of each centre's median value. RESULTS: A total of 3903 patients who underwent HAR and 3726 who had LAR for cancer were analysed. After 3 months' follow-up, the mortality benchmark in HAR for ideal and non-ideal patients was 0.0 versus 3.0 per cent, and in LAR it was 0.0 versus 2.2 per cent. Benchmark results for anastomotic leakage were 5.0 versus 6.9 per cent for HAR, and 13.6 versus 11.8 per cent for LAR. The overall morbidity benchmark in HAR was a Comprehensive Complication Index (CCI®) score of 8.6 versus 14.7, and that for LAR was CCI® score 11.9 versus 18.3. CONCLUSION: Regular comparison of individual-surgeon or -unit outcome data against benchmark thresholds may identify gaps in care quality that can improve patient outcome.

Empty pelvis syndrome: a systematic review of reconstruction techniques and their associated complications.

AIM: Empty pelvis syndrome is a major contributor to morbidity following pelvic exenteration. Several techniques for filling the pelvis have been proposed; however, there is no consensus on the best approach. We evaluated and compared the complications associated with each reconstruction technique with the aim of determining which is associated with the lowest incidence of complications related to the empty pelvis. METHOD: The systematic review protocol was prospectively registered with PROSPERO (CRD42021239307). PRISMA-P guidelines were used to present the literature. PubMed and MEDLINE were systematically searched up to 1 February 2021. A dataset containing predetermined primary and secondary outcomes was extracted. RESULTS: Eighteen studies fulfilled our criteria; these included 375 patients with mainly rectal and gynaecological cancer. Only three studies had a follow-up greater than 2 years. Six surgical interventions were identified. Mesh reconstruction and breast prosthesis were associated with low rates of small bowel obstruction (SBO), entero-cutaneous fistulas and perineal hernia. Findings for myocutaneous flaps were similar; however, they were associated with high rates of perineal wound complications. Omentoplasty was found to have a high perineal wound infection rate (40%). Obstetric balloons were found to have the highest rates of perineal wound dehiscence and SBO. Silicone expanders effectively kept small bowel out of the pelvis, although rates of pelvic collections remained high (20%). CONCLUSION: The morbidity associated with an empty pelvis remains considerable. Given the low quality of the evidence with small patient numbers, strong conclusions in favour of a certain technique and comparison of these interventions remains challenging.

Developing School-based Telehealth Programs as an Equity Strategy for Education and Health Care.

School-based telehealth programs have shown potential to address both educational and health needs of elementary students in North Carolina. A Cone Health prototype in areas of endemic poverty and low health literacy allowed for the creation of on-demand care that kept children in school, decreased early dismissals, and reduced the burden and cost of urgent health care on families.

MRI-enema for the assessment of pelvic intestinal anastomotic integrity.

AIM: Anastomotic leak causes significant morbidity for patients undergoing pelvic intestinal surgery. Fluoroscopic assessment of anastomotic integrity using water-soluble contrast enema (WSCE) is of questionable benefit over examination alone. We hypothesized that MRI-enema may be more accurate. The aim of this study was to compare MRI-enema with fluoroscopic WSCE. METHOD: Patients referred for WSCE with pelvic intestinal anastomosis and defunctioning ileostomy (including patients with suspected or known leaks) were invited to participate. WSCE and MRI-enema were undertaken within 48 h of each other. MRI sequences were performed before, during and immediately after the introduction of 400 ml of 1% gadolinium contrast solution per anus. MRI examinations were reported to protocol by two blinded gastrointestinal radiologists. A Likert-scale patient questionnaire was administered to compare patient experience. Follow-up was >12 months after ileostomy reversal. Anastomotic leak was determined by unblinded consensus of examination and radiological findings. RESULTS: Sixteen patients were recruited, with a median age of 39 years (range 22-69). Ten were men, 11 had ileoanal pouch formation and five had low anterior resection. Five patients had anastomotic leak identified by MRI and four by WSCE. The radial location of the anastomotic defect was identified in all five patients by MRI versus two on WSCE. MRI revealed additional information including contents of a widened presacral space. Patient experience was equivalent. Eleven patients eventually had ileostomy reversal without complications. CONCLUSION: MRI-enema is a feasible and tolerable alternative to WSCE and offers greater anatomical detail in the context of pelvic intestinal anastomotic leak. Larger prospective studies are required to define its potential role in the UK National Health Service.

Evolution of the management of retrorectal masses: A retrospective cohort study.

AIM: Retrorectal masses are abnormalities located anatomically in the retrorectal space. A significant proportion are asymptomatic with no malignant potential while others cause symptoms due to mechanical pressure or malignant infiltration. We reviewed and categorised the retrorectal masses encountered over a 30-year time period in a specialist colorectal hospital and describe our management algorithm for consideration by other multidisciplinary teams (MDT). METHODS: This was a retrospective analysis of consecutive patients referred between 1984-2019. A detailed review of clinical presentation, imaging features, postoperative histology and impact on morbidity and anorectal function is reported. RESULTS: A total of 143 patients with median age of 46 years and female preponderance (74%) were reviewed. The commonest presenting symptom was pain (46%) and all malignant cases had symptoms (n = 17). Over the last decade, more asymptomatic patients have presented with a retrorectal mass (33%, p = 0.04) and more patients are opting for surveillance rather than resection (33%, p = 0.013). Increasing age and lesion size were associated with malignancy (p < 0.05). Radiological features associated with malignancy included: solid/heterogeneous component, lobulated borders or locally invasive. Following surgery, complications included chronic pain (40%), poor wound healing (23%) and bowel dysfunction (10%). CONCLUSIONS: The management of retrorectal masses remains complex. There are features, both clinical and radiological, that can help determine the best management strategy. Management should be in a high-volume tertiary centre and preferably through a complex rectal cancer MDT. Long-term sequelae such as chronic pain must be highlighted to patients. We advocate the establishment of an international registry to further record and characterise these rare, potentially troublesome lesions.

Presentation, management and outcomes of ileoanal pouch cancer: a single-centre experience.

AIM: This study aimed to determine the clinical presentation, management and outcomes for patients with ileoanal pouch cancer. METHOD: Patients who were diagnosed with ileoanal pouch cancer were identified from our polyposis registry (1978-2019) and operative and referral records (2006-2019). Details of presentation, endoscopic surveillance, cancer staging and management were retrieved from hospital records. RESULTS: Eighteen patients were identified (12 with ulcerative colitis, one with Crohn's disease, three with familial adenomatous polyposis [FAP], two with dual diagnosis of FAP and inflammatory bowel disease). The median time from pouch formation to cancer diagnosis was 16.5 years (range 5-34 years) and the median age of the patient at pouch cancer diagnosis was 54 years (range 35-71 years). Eleven of the 18 patients were undergoing surveillance. Four of five FAP patients developed pouch cancer whilst on surveillance. Eight patients were asymptomatic at the time of pouch cancer diagnosis. Two patients had complete clinical response following chemoradiotherapy. Fourteen patients underwent pouch excision surgery (eight with exenteration). Median survival was 54 months; however, only eight patients had outcomes available beyond 24 months follow-up. CONCLUSIONS: Pouch cancer can occur in patients despite routine surveillance and without symptoms, and survival is poor. Centralization of 'high-risk' patients who require surveillance is recommended and a low threshold for referral to centres that can provide expert investigation and management is advised.

Responding to sustained poor outcomes in the management of non-communicable diseases (NCDs): an "incident control" approach is needed to improve and protect population health.

In 2017 Public Health England were asked to assist with investigating why 1-year cancer survival rates appeared lower than expected in a local area. We identified 50 premature deaths that surveillance data suggested we would not expect. These deaths highlighted a gap in recognising and responding to this kind of systematic non communicable disease (NCD) outcome variation. We hypothesise that the lack of a universally agreed systematic response to variations is not only counter-intuitive, but wholly unacceptable where non-communicable diseases (NCDs) rather than infectious diseases have become the leading causes of illness and death worldwide. In the United Kingdom (UK) alone over 89% of mortality in 2014 was attributable to NCDs. We argue that a new approach is urgently needed to turn the curve on NCD outcome variation to protect and improve the public's health. We set out a definition of an NCD "incident" and propose a phased approach that could be used to respond to local variation in NCD outcomes.Establishing parity of response for local variations in NCD outcomes and CD control is critically important. Although evidence shows that prevention and early intervention will make the biggest difference to NCD incidence, collective local whole health economy response, exploiting the wealth of surveillance data in real time, needs to be at the heart of responding to variations in NCD outcomes at a population level. We argue that local and national public health agencies should mandate a standardised 'incident' response to significant changes in outcomes from NCD to mitigate and reduce the loss of quality life.

Perioperative risk prediction in the era of enhanced recovery: a comparison of POSSUM, ACPGBI, and E-PASS scoring systems in major surgical procedures of the colorectal surgeon.

PURPOSE: This study aims to determine whether traditional risk models can accurately predict morbidity and mortality in patients undergoing major surgery by colorectal surgeons within an enhanced recovery program. METHODS: One thousand three hundred eighty patients undergoing surgery performed by colorectal surgeons in a single UK hospital (2008-2013) were included. Six risk models were evaluated: (1) Physiology and Operative Severity Score for the enumeration of Mortality and Morbidity (POSSUM), (2) Portsmouth POSSUM (P-POSSUM), (3) ColoRectal (CR-POSSUM), (4) Elderly POSSUM (E-POSSUM), (5) the Association of Great Britain and Ireland (ACPGBI) score, and (6) modified Estimation of Physiologic Ability and Surgical Stress Score (E-PASS). Model accuracy was assessed by observed to expected (O:E) ratios and area under Receiver Operating Characteristic curve (AUC). RESULTS: Eleven patients (0.8%) died and 143 patients (10.4%) had a major complication within 30 days of surgery. All models overpredicted mortality and had poor discrimination: POSSUM 8.5% (O:E 0.09, AUC 0.56), P-POSSUM 2.2% (O:E 0.37, AUC 0.56), CR-POSSUM 7.1% (O:E 0.11, AUC 0.61), and E-PASS 3.0% (O:E 0.27, AUC 0.46). ACPGBI overestimated mortality in patients undergoing surgery for cancer 4.4% (O:E = 0.28, AUC = 0.41). Predicted morbidity was also overestimated by POSSUM 32.7% (O:E = 0.32, AUC = 0.51). E-POSSUM overestimated mortality (3.25%, O:E 0.57 AUC = 0.54) and morbidity (37.4%, O:E 0.30 AUC = 0.53) in patients aged ≥ 70 years and over. CONCLUSION: All models overestimated mortality and morbidity. New models are required to accurately predict the risk of adverse outcome in patients undergoing major abdominal surgery taking into account the reduced physiological and operative insult of laparoscopic surgery and enhanced recovery care.

Lymphangiogenesis in rat asthma model.

Although bronchial angiogenesis has been well documented in allergic asthma, lymphangiogenesis has not been widely studied. Therefore, we evaluated changes in lung lymphatics in a rat model of allergen-induced asthma using house dust mite (Der p 1; 100 µg/challenge). Additionally, properties of isolated lung lymphatic endothelial cells (CD45-, CD141+, LYVE-1+, Prox-1+) were studied in vitro. Three weeks after the onset of intranasal allergen exposure (twice-weekly), an increase in the number of lung lymphatic vessels was measured (34% increase) by lung morphometry. New lymphatic structures were seen predominantly in the peribronchial and periarterial interstitial space but also surrounding large airways. Isolated lymphatic endothelial cells from sensitized lungs showed enhanced proliferation (% Ki67+), chemotaxis, and tube formation (number and length) compared to lymphatic endothelial cells isolated from naive rat lungs. This hyper-proliferative lymphangiogenic phenotype was preserved through multiple cell passages (2-8). Lymphatic endothelial cells isolated from naive and HDM-sensitized rats produced similar in vitro levels of VEGF-C, VEGF-D, and VEGFR3 protein, each recognized as critical lymphangiogenic factors. Inhibition with anti-VEGFR (axitinib, 0.1 µM) blocked proliferation and chemotaxis. Results suggest that in vivo sensitization causes fundamental changes to lymphatic endothelium, which are retained in vitro, and may relate to VEGFR downstream signaling.