Biallelic TLR4 deficiency in humans.

BACKGROUND: Toll-like receptors (TLRs) mediate functions for host defense and inflammatory responses. TLR4 recognizes LPS, a component of gram-negative bacteria as well as host-derived endogenous ligands such as S100A8 and S100A9 proteins. OBJECTIVE: We sought to report phenotype and cellular function of individuals with complete TLR4 deficiency. METHODS: We performed genome sequencing and investigated exome and genome sequencing databases. Cellular responses were studied on primary monocytes, macrophages, and neutrophils, as well as cell lines using flow cytometry, reporter, and cytokine assays. RESULTS: We identified 2 individuals in a family of Qatari origin carrying a homozygous stop codon variant p.Q188X in TLR4 presenting with a variable phenotype (asymptomatic and inflammatory bowel disease consistent with severe perianal Crohn disease). A third individual with homozygous p.Y794X was identified in a population database. In contrast to hypomorphic polymorphisms p.D299G and p.T399I, the variants p.Q188X and p.Y794X completely abrogated LPS-induced cytokine responses whereas TLR2 response was normal. TLR4 deficiency causes a neutrophil CD62L shedding defect, whereas antimicrobial activity toward intracellular Salmonella was intact. CONCLUSIONS: Biallelic TLR4 deficiency in humans causes an inborn error of immunity in responding to LPS. This complements the spectrum of known primary immunodeficiencies, in particular myeloid differentiation primary response 88 (MYD88) or the IL-1 receptor-associated kinase 4 (IRAK4) deficiency that are downstream of TLR4 and TLR2 signaling.

Early management of acute severe UC in the biologics era: development and international validation of a prognostic clinical index to predict steroid response.

OBJECTIVES: We aimed to determine whether changes in acute severe colitis (ASC) management have translated to improved outcomes and to develop a simple model predicting steroid non-response on admission. DESIGN: Outcomes of 131 adult ASC admissions (117 patients) in Oxford, UK between 2015 and 2019 were compared with data from 1992 to 1993. All patients received standard treatment with intravenous corticosteroids and endoscopic disease activity scoring (Ulcerative Colitis Endoscopic Index of Severity (UCEIS)). Steroid non-response was defined as receiving medical rescue therapy or surgery. A predictive model developed in the Oxford cohort was validated in Australia and India (Gold Coast University Hospital 2015-2020, n=110; All India Institute of Medical Sciences, New Delhi 2018-2020, n=62). RESULTS: In the 2015-2019 Oxford cohort, 15% required colectomy during admission vs 29% in 1992-1993 (p=0.033), while 71 (54%) patients received medical rescue therapy (27% ciclosporin, 27% anti-tumour necrosis factor, compared with 27% ciclosporin in 1992-1993 (p=0.0015). Admission C reactive protein (CRP) (false discovery rate, p=0.00066), albumin (0.0066) and UCEIS scores (0.015) predicted steroid non-response. A four-point model was developed involving CRP of ≥100 mg/L (one point), albumin of ≤25 g/L (one point), and UCEIS score of ≥4 (1 point) or ≥7 (2 points). Patients scoring 0, 1, 2, 3 and 4 in the validation cohorts had steroid response rates of 100, 75.0%, 54.9%, 18.2% and 0%, respectively. Scoring of ≥3 was 84% (95% CI 0.70 to 0.98) predictive of steroid failure (OR 11.9, 95% CI 10.8 to 13.0). Colectomy rates in the validation cohorts were were 8%-11%. CONCLUSIONS: Emergency colectomy rates for ASC have halved in 25 years to 8%-15% worldwide. Patients who will not respond to corticosteroids are readily identified on admission and may be prioritised for early intensification of therapy.

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

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.

Does Smoking Cessation Reduce Surgical Recurrence After Primary Ileocolic Resection for Crohn's Disease?

BACKGROUND: Tobacco smoking is a known risk factor for recurrence of Crohn's disease after surgical resection. OBJECTIVE: This study assessed the effect of smoking cessation on long-term surgical recurrence after primary ileocolic resection for Crohn's disease. DESIGN: A retrospective review of a prospectively maintained database was conducted. SETTINGS: Patient demographic data and medical and surgical details were combined from 2 specialist centers. After ethical approval, patients were contacted in case of missing data regarding smoking habit. PATIENTS: All patients undergoing ileocolic resection between 2000 and 2012 for histologically confirmed Crohn's disease were included. Those with previous intestinal resection, strictureplasty for Crohn's disease, leak after ileocolic resection, or who were never reversed were excluded. MAIN OUTCOME MEASURES: The primary end point was surgical recurrence measured by Kaplan-Meier survival analysis and secondary medical therapy at time of follow-up. RESULTS: Over a 12-year period, 290 patients underwent ileocolic resection. Full smoking data were available for 242 (83%) of 290 patients. There were 169 nonsmokers (70%; group 1), 42 active smokers at the time of ileocolic resection who continued smoking up to last follow-up (17%; group 2), and 31 (13%) who quit smoking after ileocolic resection (group 3). The median time of smoking exposure after ileocolic resection for group 3 was 3 years (interquartile range, 0-6 y), and median follow-up time for the whole group was 112 months (9 mo; interquartile range, 84-148 mo). Kaplan-Meier survival analysis showed a significantly higher surgical recurrence rate for group 2 compared with group 3 (16/42 (38%) vs 3/31 (10%); p = 0.02; risk ratio = 3.9 (95% CI, 1-12)). In addition, significantly more patients in group 2 without surgical recurrence received immunomodulatory maintenance therapy compared with group 3 (12/26 (46%) vs 4/28 (14%); p = 0.01; risk ratio = 3.2 (95% CI, 1-9)). LIMITATIONS: The study was limited by its retrospective design and small number of patients. CONCLUSIONS: Smoking cessation after primary ileocolic resection for Crohn's disease may significantly reduce long-term risk of surgical recurrence and is associated with less use of maintenance therapy. See Video Abstract at http://links.lww.com/DCR/B86. ¿DEJAR DE FUMAR REDUCE LA RECURRENCIA QUIRÚRGICA DESPUÉS DE LA RESECCIÓN ILEOCÓLICA PRIMARIA PARA LA ENFERMEDAD DE CROHN?: Fumar tabaco es un factor de riesgo conocido para la recurrencia de la enfermedad de Crohn después de la resección quirúrgica.Evaluar el efecto de dejar de fumar en la recurrencia quirúrgica a largo plazo después de la resección ileocólica primaria para la enfermedad de Crohn.Revisión retrospectiva de una base de datos mantenida prospectivamente.Se combinaron datos demográficos del paciente, así como detalles médicos y quirúrgicos de dos centros especializados. Después de la aprobación ética, se contactó a los pacientes en caso de falta de datos sobre el hábito de fumar.Todos los pacientes sometidos a resección ileocólica entre 2000 y 2012 por enfermedad de Crohn confirmada histológicamente. Se excluyeron aquellos con resección intestinal previa, estenosis por enfermedad de Crohn, fuga después de resección ileocólica o que nunca se revirtieron.La principal variable fue la recurrencia quirúrgica medida por análisis de supervivencia de Kaplan-Meier, terapia médica secundaria en el momento del seguimiento.Durante un período de 12 años, 290 pacientes fueron sometidos a resección ileocólica. Se dispuso de datos completos sobre el tabaquismo para 242/290 (83%). Hubo 169 no fumadores (70%) (grupo 1), 42 (17%) fumadores activos en el momento de la resección ileocólica que continuaron fumando hasta el último seguimiento (grupo 2) y 31 (13%) que dejaron de fumar después de resección ileocólica (grupo 3). La mediana del tiempo de exposición al tabaquismo después de la resección ileocólica para el grupo 3 fue de 3 años (IQR 0-6) y la mediana del tiempo de seguimiento para todo el grupo fue de 112 meses (9 años) (IQR 84-148). El análisis de supervivencia de Kaplan-Meier mostró una tasa de recurrencia quirúrgica significativamente mayor para el grupo 2 en comparación con el grupo 3 (16/42 (38%) frente a 3/31 (10%), p = 0.02; razón de riesgo 3.9 (IC 95% 1-12)). Además, un número significativamente mayor de pacientes del grupo 2 sin recurrencia quirúrgica recibieron terapia de mantenimiento inmunomoduladora en comparación con el grupo 3 (12/26 (46%) frente a 4/28 (14%), p = 0.01; razón de riesgo 3.2 (IC 95% 1-9)).Diseño retrospectivo y pequeño número de pacientes.Dejar de fumar después de la resección ileocólica primaria para la enfermedad de Crohn puede reducir significativamente el riesgo a largo plazo de recurrencia quirúrgica y se asocia con un menor uso del tratamiento de mantenimiento. Consulte Video Resumen en http://links.lww.com/DCR/B86. (Traducción-Dr. Gonzalo Federico Hagerman).

The rectal remnant after total colectomy for colitis - intra-operative,post-operative and longer-term considerations.

OBJECTIVES: Acute severe colitis requires surgery in around 30% of the cases. Total colectomy with ileostomy is the standard procedure with distinct advantages to a laparoscopic approach. Less agreement exists regarding the formation or configuration of the retained rectal stump and its short-term and long-term management. In this review, aspects of management of the rectal remnant, including perioperative considerations, potential complications, medical treatment, surveillance and implications for proctectomy and reconstructive surgery are explored. METHODS: A thorough literature review exploring the PubMed and EMBASE databases was undertaken to clarify the evidence base surrounding areas of controversy in the surgical approach to acute severe colitis. In particular, focus was given to evidence surrounding management of the rectal remnant. RESULTS: There is a paucity of high quality evidence for optimal management of the rectal stump following colectomy, and randomised trials are lacking. Establishment of laparoscopic colectomy has been associated with distinct advantages as well as the emergence of unique considerations, including those specific to rectal remnant management. CONCLUSIONS: Early surgical involvement and a multidisciplinary approach to the management of acute severe colitis are advocated. Laparoscopic subtotal colectomy and ileostomy should be the operation of choice, with division of the rectum at the pelvic brim leaving a closed intraperitoneal remnant. If the rectum is severely inflamed, a mucus fistula may be useful, and an indwelling rectal catheter is probably advantageous to reduce the complications associated with stump dehiscence. Patients electing not to proceed to proctectomy should undergo surveillance for dysplasia of the rectum.

Methylene blue fluorescence of the ureter during colorectal surgery.

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.

Surgery versus surveillance in ulcerative colitis patients with endoscopically invisible low-grade dysplasia: a cost-effectiveness analysis.

BACKGROUND AND AIMS: There is uncertainty regarding the optimal management of endoscopically invisible (flat) low-grade dysplasia in ulcerative colitis. Such a finding does not currently provide an automatic indication for colectomy; however, a recommendation of surveillance instead of surgery is controversial. The aim of this study was to determine the clinical and cost-effectiveness of colonoscopic surveillance versus colectomy for endoscopically invisible low-grade dysplasia of the colon in ulcerative colitis. METHODS: A Markov model was used to evaluate the costs and health outcomes of surveillance and surgery over a 20-year timeframe. Outcomes evaluated were life years gained and quality-adjusted life years (QALYs). Cohorts of patients aged 25 to 75 were modeled, including estimates from a validated surgical risk calculator and considering none, 1, or both of 2 key comorbidities: heart failure and obstructive airway disease. RESULTS: Surveillance is associated with more life years and QALYs compared with surgery from age 61 for those with no comorbidities, age 51 for those with 1 comorbidity and age 25 for those with 2 comorbidities. At the current United Kingdom National Institute for Health and Care Excellence threshold of $25,800 per QALY, ongoing surveillance was cost-effective at age 65 in those without comorbidities and at age 60 in those with either 1 or more comorbidities. CONCLUSIONS: Surveillance can be recommended from age 65 for those with no comorbidities; however, in younger patients with typical postsurgical quality of life, colectomy may be more effective clinically and more cost-effective. The results were sensitive to the colorectal cancer incidence rate in patients under surveillance and to quality of life after surgery.

What To Do With Lateral Nodal Disease in Low Locally Advanced Rectal Cancer? A Call for Further Reflection and Research.

BACKGROUND: There remains a lack of international consensus on the appropriate management of lateral nodal disease. Although the East manages this more aggressively with lateral lymph node dissections, the West aims to eradicate small-volume disease with neoadjuvant chemoradiotherapy and lateral nodal disease is not considered for routine surgical treatment. However, recent studies have shown that, despite neoadjuvant treatment, a significant number of patients with lateral nodal disease develop local recurrence in the lateral compartment after total mesorectal excision. OBJECTIVE: The aim of this study is to assess the role of the pretreatment features of lateral nodes on MRI in regard to local recurrence. DESIGN: All patients operated on for low locally advanced rectal cancer over a 5-year period were evaluated retrospectively. SETTINGS: This study was conducted at a single expert center. PATIENTS: The MRIs of a total of 313 patients were reviewed, and only those with rectal cancers up to 8 cm from the anorectal junction, measured on MRI, were selected. This left 185 patients; of these, 58 patients had clinical T1 or T2 tumors as assessed on MRI, identifying 127 patients who had cT3/T4 tumors that were included in this study. MAIN OUTCOME MEASURES: The primary outcomes measured were lateral local recurrence and multivariate analyses. RESULTS: The lateral local recurrence rate was significantly higher (33.3% 4-year rate) in patients with nodes larger than 10 mm than in patients with smaller nodes (10.1%, p = 0.03), despite patients being irradiated in the lateral compartment. LIMITATIONS: Because this is a relatively uncommon disease, patient numbers are low, and a multicenter study is needed to further address lateral nodal disease in low rectal cancer. CONCLUSIONS: Chemoradiotherapy with total mesorectal excision might not be sufficient in a selected group of patients. Further research is needed about which pretreatment features of the lateral nodes predict local recurrence and what is needed to prevent these from developing. See Video Abstract at http://links.lww.com/DCR/A338.

Management of Tumors of the Ischiorectal Fossa: The Role of Percutaneous Biopsy.

BACKGROUND: Noninflammatory masses in the ischiorectal fossa are rare. OBJECTIVE: This study aimed to review our experience with ischiorectal fossa tumors and to address the question of whether percutaneous biopsy should be undertaken. DESIGN: This is a retrospective study. SETTINGS: This study was conducted at a tertiary institution. PATIENTS: From April 2007 to November 2014, all consecutive ischiorectal fossa masses treated in a referral center were retrospectively reviewed. They were all presented and discussed in a multidisciplinary team meeting. Magnetic resonance imaging was performed in all the patients. Inflammatory pathologies, such as abscess, were excluded from the analysis. INTERVENTIONS: Percutaneous biopsy and surgical excision of ischiorectal fossa tumors were reviewed. MAIN OUTCOME MEASURES: Perioperative, pathological, and oncological outcomes were measured. RESULTS: Eleven patients were identified (8 female; median age, 50 years; range, 25-90). Percutaneous biopsy was undertaken in 8 patients. All biopsies were diagnostic and altered preoperative management in 3 cases (aggressive angiomyxoma (n = 2), desmoid fibromatosis (n = 1)). Overall final diagnosis was benign in 3 patients, locally aggressive neoplasm in 3, and malignant in 5 cases (leiomyosarcomas (n = 2), liposarcomas (n = 2), and angiomyosarcoma (n = 1)). Surgical approaches were perineal in 8 patients, abdominoperineal in 1 patient, and totally abdominal in 1 patient. One patient (age 90 years) was managed nonsurgically. After resection, 2 positive margins were observed (R1 rate, 20%). After a mean follow-up of 24.3 months, 3 patients have experienced local recurrence, which required further surgery in 2 cases. LIMITATIONS: This study is limited by the small number of patients. CONCLUSIONS: Noninflammatory masses in the ischiorectal fossa are rare, but they are commonly malignant and should be imaged by MRI. Unless the radiological appearances are diagnostic, percutaneous biopsy is recommended and alters management in about one-third of cases.

Near-infrared (NIR) perfusion angiography in minimally invasive colorectal surgery.

BACKGROUND: Anastomotic leakage is a devastating complication of colorectal surgery. However, there is no technology indicative of in situ perfusion of a laparoscopic colorectal anastomosis. METHODS: We detail the use of near-infrared (NIR) laparoscopy (PinPoint System, NOVADAQ, Canada) in association with fluorophore [indocyanine green (ICG), 2.5 mg/ml] injection in 30 consecutive patients who underwent elective minimally invasive colorectal resection using the simultaneous appearance of the cecum or distal ileum as positive control. RESULTS: The median (range) age of the patients was 64 (40-81) years with a median (range) BMI of 26.7 (20-35.5) kg/m(2). Twenty-four patients had left-sided resections (including six low anterior resections) and six had right-sided resections. Of the total, 25 operations were cancer resections and five were for benign disease [either diverticular strictures (n = 3) or Crohn's disease (n = 2)]. A high-quality intraoperative ICG angiogram was achieved in 29/30 patients. After ICG injection, median (range) time to perfusion fluorescence was 35 (15-45) s. Median (range) added time for the technique was 5 (3-9) min. Anastomotic perfusion was documented as satisfactory in every successful case and encouraged avoidance of defunctioning stomas in three patients with low anastomoses. There were no postoperative anastomotic leaks. CONCLUSION: Perfusion angiography of colorectal anastomosis at the time of their laparoscopic construction is feasible and readily achievable with minimal added intraoperative time. Further work is required to determine optimum sensitivity and threshold levels for assessment of perfusion sufficiency, in particular with regard to anastomotic viability.

Surgical Planning in Penetrating Abdominal Crohn's Disease.

Crohn's disease (CD) is increasing globally, and the disease location and behavior are changing toward more colonic as well as inflammatory behavior. Surgery was previously mainly performed due to ileal/ileocaecal location and stricturing behavior, why many anticipate the surgical load to decrease. There are, however, the same time data showing an increasing complexity among patients at the time of surgery with an increasing number of patients with the abdominal perforating disease, induced by the disease itself, at the time of surgery and thus a more complex surgery as well as the post-operative outcome. The other major cause of abdominal penetrating CD is secondary to surgical complications, e.g., anastomotic dehiscence or inadvertent enterotomies. To improve the care for patients with penetrating abdominal CD in general, and in the peri-operative phase in particular, the use of multidisciplinary team discussions is essential. In this study, we will try to give an overview of penetrating abdominal CD today and how this situation may be handled. Proper surgical planning will decrease the risk of surgically induced penetrating disease and improve the outcome when penetrating disease is already established. It is important to evaluate patients prior to surgery and optimize them with enteral nutrition (or parenteral if enteral nutrition is ineffective) and treat abdominal sepsis with drainage and antibiotics.

Hartmann's Reversal: Controversies of a Challenging Operation.

Purpose: Hartmann's reversal is a complex operation with a high morbidity rate. Minimally invasive surgery has been used to reduce the impact of surgery on fragile patients. The aim of this comparative study is to look at the results of Hartmann's reversal procedures with different approaches. Methods: All the patients who underwent Hartmann's reversal were collected retrospectively (124 cases). Sixty-four patients (50.4%) had an open operation, 6 cases (5%) were treated with a conventional laparoscopic approach, 34 patients (28.1%) underwent single incision laparoscopic surgery (SILS), and 20 (16.5%) required other additional trocars. Results: SILS operations were slightly longer than the open procedures (175 min vs 150 min), with the same rate of postoperative complications and reoperations (p = 0.83 and p = 0.42), but with a shorter hospital stay (5 days p = 0.007). Age (p = 0.03), long operative time (p = 0.01), and ASA score (p = 0.05) were identified as independent factors affecting postoperative morbidity. The grade of adhesions caused a longer operative time (p = 0.001) and a higher risk of conversion (p < 0.001), and short rectal stump increased the risk of protective loop ileostomy (p = 0.008). Patients with grade 2-3 of adhesions had a longer length of stay (p = 0.05). Conclusions: Minimally invasive procedures had a shorter hospital stay and did not show any increase in morbidity rate when compared with open cases. Age, longer operative time, and ASA score increased the risk of postoperative complications. Furthermore, patients with a short rectal stump had a higher chance of having a defunctioning ileostomy.

Influence of incorrect staging of colorectal carcinoma on oncological outcome: are we playing safely?

Accurate preoperative staging of colorectal cancers is critical in selecting patients for neoadjuvant therapy prior to resection. Inaccurate staging, particularly understaging, may lead to involved resection margins and poor oncological outcomes. Our aim is to determine preoperative imaging accuracy of colorectal cancers compared to histopathology and define the effect of inaccurate staging on patient selection for neoadjuvant treatment(NT). Staging and treatment were determined for patients undergoing colorectal resections for adenocarcinomas in a single tertiary centre(2016-2020). Data were obtained for 948 patients. The staging was correct for both T and N stage in 19.68% of colon cancer patients. T stage was under-staged in 18.58%. At resection, 23 patients (3.36%) had involved pathological margins; only 7 of which had been predicted by pre-operative staging. However, the staging was correct for both T and N stage in 53.85% of rectal cancer patients. T stage was understaged in 26.89%. Thirteen patients had involved(R1)margins; T4 had been accurately predicted in all of these cases. There was a general trend in understaging both the tumor and lymphonodal involvement (T p < 0.00001 N p < 0.00001) causing a failure in administrating NT in 0.1% of patients with colon tumor, but not with rectal cancer. Preoperative radiological staging tended to understage both colonic and rectal cancers. In colonic tumours this may lead to a misled opportunity to treat with neoadjuvant therapy, resulting in involved margins at resection.

The impact and restoration of colorectal services during the coronavirus disease 2019 pandemic: A view from Oxford.

Aim: The coronavirus pandemic has significantly disrupted the way we deliver healthcare worldwide. We have been flexible and creative in order to continue providing elective colorectal cancer operations and to restart services for benign cases during the recovery period of the pandemic. In this paper, we describe the impact of coronavirus on our elective services and how we have implemented new patient pathways to allow us to continue providing patient care. Patients and Methods: Data on major colorectal elective resections were prospectively collected in an Enhanced Recovery After Surgery (ERAS) database. Data on the number of proctology cases and telemed appointments were collected from the hospital theatre information management system and electronic patient record system, respectively. Results: During the pandemic, there was a complete shift towards cancer cases, with benign services and proctology cases being placed on hold. Hospital length of stay was reduced. We implemented earlier hospital discharge and more intense telephone follow-up after elective major surgery. This has not resulted in an increase in postoperative complications, nor any increase in readmission to hospital. During the recovery phase, we have introduced a higher proportion of telemed consultations, including one-stop telemed proctology clinics, resulting in straight to tests or investigations. Conclusion: We have created a streamlined multidisciplinary pathway to reinstate our elective colorectal services as soon as possible and to minimise potential harm caused to patients whose treatment have been delayed. We anticipate many of these changes will be permanently incorporated into our clinical practice once the pandemic is over.

A case-control study of colorectal cancer detection by quantification of DNA isolated from directly collected exfoliated colonocytes.

This pilot study aimed to assess an original test based on the analysis of exfoliated colonocytes as a new approach to colorectal cancer (CRC) detection. DNA was isolated from exfoliated cells collected from the surface of the rectal mucosa by a standardized minimally invasive procedure in a case-control trial involving 66 patients with CRC diagnosis and 110 healthy volunteers (age 50-70). PicoGreen staining and quantitative real-time PCR (QRTPCR) were used for DNA quantification. Mean DNA scores in microg/ml obtained for the control and cancer groups were 2.1 (95% CI 1.7-2.5) and 9.0 (CI 6.7-11.2) respectively (p < 0.001) for PicoGreen and 0.8 (CI 0.6-0.9) and 3.8 (CI 1.9-5.7) respectively (p = 0.003) for QRTPCR. The PicoGreen assay better detected CRC presence. At DNA score cut-off point of 2.5 microg/ml this assay gave sensitivities of 77.8% (CI 52.4-93.6) for proximal tumours, 91.4% (CI 76.9-98.2) for distal CRC and 86.8% (CI 74.7-94.5) for all CRC with specificity at 74.0% (CI 64.0-82.4). Increasing the cut-off point to 5.0 microg/ml resulted in sensitivities of 38.9% (CI 17.3-64.3) for proximal tumours, 71.4% (CI 53.7-85.4) for distal CRC and 60.4% (CI 46.0-73.5) for all CRC. Specificity for this cut-off point increased to 94.8% (CI 88.3-98.3). The new procedure of exfoliated cell collection from the surface of the rectal mucosa is a simple, safe and well-tolerated technique providing high quality cells. These early results suggest that exfoliated cell collection in combination with DNA quantification can potentially be employed as a tool for CRC early detection.

Increased frequency of regulatory T cells in peripheral blood and tumour infiltrating lymphocytes in colorectal cancer patients.

Recent results have shown a correlation between survival and frequency of tumour infiltrating T lymphocytes in colorectal cancer patients. However, it remains unclear whether the frequency of regulatory T cells is higher in colorectal cancer as compared to normal colon. To address this question we analysed the frequency and function of regulatory T cells in the peripheral blood and tumour infiltrating lymphocytes of colorectal cancer patients. The proportion of regulatory T cells in the peripheral blood of colorectal cancer patients (mean 8%) was significantly higher than that in normal controls (mean 2.2%). There were significantly more regulatory T cells in tumour infiltrating lymphocytes (mean 19.2%) compared to lymphocytes from an autologous non-malignant portion of the colon (mean 9%). Regulatory T cells from colorectal cancer patients were FOXP3 positive and suppressed the proliferation of autologous CD4+ CD25- cells. A higher density of tumour infiltrating regulatory T cells was found in patients with advanced as compared to early disease. These results support the hypothesis that increased numbers of regulatory T cells in the blood and tumours of colorectal cancer patients may influence the immune response against cancer and suggest that strategies to overcome regulatory T cell activity may be beneficial in the treatment of human colorectal cancer.

Intestinal stem cells and intestinal homeostasis in health and in inflammation: A review.

BACKGROUND: The human intestine is a complex group of organs, highly specialized in processing food and providing nutrients to the body. It is under constant threat from microbials and toxins and has therefore developed a number of protective mechanisms. One important mechanism is the constant shedding of epithelial cells into the lumen; another is the production and maintenance of a double-layered mucous boundary in which there is continuous sampling of the luminal microbiota and a persistent presence of antimicrobial enzymes. However, the gut needs commensal bacteria to effectively break down food into absorbable nutrients, which necessitates constant communication between the luminal bacteria and the intestinal immune cells in homeostasis. Disruption of homeostasis, for whatever reason, will give rise to (chronic) inflammation. DISCUSSION: Both medical and surgical management of this disruption is discussed.