Rare de novo gain-of-function missense variants in DOT1L are associated with developmental delay and congenital anomalies.

Misregulation of histone lysine methylation is associated with several human cancers and with human developmental disorders. DOT1L is an evolutionarily conserved gene encoding a lysine methyltransferase (KMT) that methylates histone 3 lysine-79 (H3K79) and was not previously associated with a Mendelian disease in OMIM. We have identified nine unrelated individuals with seven different de novo heterozygous missense variants in DOT1L through the Undiagnosed Disease Network (UDN), the SickKids Complex Care genomics project, and GeneMatcher. All probands had some degree of global developmental delay/intellectual disability, and most had one or more major congenital anomalies. To assess the pathogenicity of the DOT1L variants, functional studies were performed in Drosophila and human cells. The fruit fly DOT1L ortholog, grappa, is expressed in most cells including neurons in the central nervous system. The identified DOT1L variants behave as gain-of-function alleles in flies and lead to increased H3K79 methylation levels in flies and human cells. Our results show that human DOT1L and fly grappa are required for proper development and that de novo heterozygous variants in DOT1L are associated with a Mendelian disease.

Resonant Ultrasound Spectroscopy for Irregularly Shaped Samples and Its Application to Uranium Ditelluride.

Resonant ultrasound spectroscopy (RUS) is a powerful technique for measuring the full elastic tensor of a given material in a single experiment. Previously, this technique was practically limited to regularly shaped samples such as rectangular parallelepipeds, spheres, and cylinders [W. M. Visscher et al. J. Acoust. Soc. Am. 90, 2154 (1991)JASMAN0001-496610.1121/1.401643]. We demonstrate a new method for determining the elastic moduli of irregularly shaped samples, extending the applicability of RUS to a much larger set of materials. We apply this new approach to the recently discovered unconventional superconductor UTe_{2} and provide its elastic tensor at both 300 and 4 kelvin.

De Novo Variants in CNOT1, a Central Component of the CCR4-NOT Complex Involved in Gene Expression and RNA and Protein Stability, Cause Neurodevelopmental Delay.

CNOT1 is a member of the CCR4-NOT complex, which is a master regulator, orchestrating gene expression, RNA deadenylation, and protein ubiquitination. We report on 39 individuals with heterozygous de novo CNOT1 variants, including missense, splice site, and nonsense variants, who present with a clinical spectrum of intellectual disability, motor delay, speech delay, seizures, hypotonia, and behavioral problems. To link CNOT1 dysfunction to the neurodevelopmental phenotype observed, we generated variant-specific Drosophila models, which showed learning and memory defects upon CNOT1 knockdown. Introduction of human wild-type CNOT1 was able to rescue this phenotype, whereas mutants could not or only partially, supporting our hypothesis that CNOT1 impairment results in neurodevelopmental delay. Furthermore, the genetic interaction with autism-spectrum genes, such as ASH1L, DYRK1A, MED13, and SHANK3, was impaired in our Drosophila models. Molecular characterization of CNOT1 variants revealed normal CNOT1 expression levels, with both mutant and wild-type alleles expressed at similar levels. Analysis of protein-protein interactions with other members indicated that the CCR4-NOT complex remained intact. An integrated omics approach of patient-derived genomics and transcriptomics data suggested only minimal effects on endonucleolytic nonsense-mediated mRNA decay components, suggesting that de novo CNOT1 variants are likely haploinsufficient hypomorph or neomorph, rather than dominant negative. In summary, we provide strong evidence that de novo CNOT1 variants cause neurodevelopmental delay with a wide range of additional co-morbidities. Whereas the underlying pathophysiological mechanism warrants further analysis, our data demonstrate an essential and central role of the CCR4-NOT complex in human brain development.

Use of Temporary Abdominal Closure in Non-Trauma Surgery: A Cohort Study.

BACKGROUND: Damage control surgery in trauma is widely used but the evidence for the use of laparostomy in non-trauma abdominal emergencies is limited. This study aimed to characterise outcomes in emergency abdominal surgery by comparing laparostomy to one-stage laparotomy for patients of similar illness severity. METHODS: A retrospective study of adult patients requiring emergency abdominal surgery and post-operative intensive care stay was performed between 2016 and 2020 at a major Australian metropolitan hospital. Case selection was from a prospectively maintained database, and case notes were reviewed. Patients having delayed abdominal closure were compared with those having one-stage abdominal closure. The primary outcome was odds of in-hospital mortality. The secondary outcomes included intensive care unit length of stay (LOS), overall hospital LOS, definitive stoma rate and discharge destination. Multivariable logistic regression analysis was performed to adjust for potentially confounding variables. RESULTS: Two hundred and eighteen patients met inclusion criteria (80 laparostomy and 138 non-laparostomy). The most common indications for laparostomy were bowel ischaemia (41.3%), sepsis (26.3%) and physiological instability (22.5%). There was no evidence of difference in odds of in-hospital mortality between groups (adjusted OR = 1.67, CI: 0.85-3.28; p = 0.138). Patients requiring laparostomy had a slightly longer median ICU LOS (4 vs. 3 days; p < 0.001), similar median hospital LOS (19 vs. 14 days, p = 0.245) and similar discharge destination. There was no difference in stoma rate (35.0% vs. 35.5%). CONCLUSION: Compared with standard one-stage laparotomy, laparostomy resulted in similar odds of in-hospital mortality in emergency abdominal surgery patients requiring intensive care.

Novel PPP1R13L variant expands the phenotype of a rare cardiocutaneous syndrome.

PPP1R13L-associated cardiocutaneous syndrome is an autosomal recessive condition that presents with life-threatening dilated cardiomyopathy in early childhood, with or without features of inflammation on cardiac histology. There is also a variably expressed ectodermal phenotype.

Further characterization of Borjeson-Forssman-Lehmann syndrome in females due to de novo variants in PHF6.

While inherited hemizygous variants in PHF6 cause X-linked recessive Borjeson-Forssman-Lehmann syndrome (BFLS) in males, de novo heterozygous variants in females are associated with an overlapping but distinct phenotype, including moderate to severe intellectual disability, characteristic facial dysmorphism, dental, finger and toe anomalies, and linear skin pigmentation. By personal communication with colleagues, we assembled 11 additional females with BFLS due to variants in PHF6. We confirm the distinct phenotype to include variable intellectual disability, recognizable facial dysmorphism and other anomalies. We observed skewed X-inactivation in blood and streaky skin pigmentation compatible with functional mosaicism. Variants occurred de novo in 10 individuals, of whom one was only mildly affected and transmitted it to her more severely affected daughter. The mutational spectrum comprises a two-exon deletion, five truncating, one splice-site and three missense variants, the latter all located in the PHD2 domain and predicted to severely destabilize the domain structure. This observation supports the hypothesis of more severe variants in females contributing to gender-specific phenotypes in addition to or in combination with effects of X-inactivation and functional mosaicism. Therefore, our findings further delineate the clinical and mutational spectrum of female BFLS and provide further insights into possible genotype-phenotype correlations between females and males.

Is increasing nodal count associated with improved recurrence-free and overall survival following standard right hemicolectomy for colon cancer?

BACKGROUND AND OBJECTIVES: Increasing lymph node harvest for right-sided colon cancer is associated with improved overall survival (OS), but most relevant studies failed to report the extent of resection. We examined the association between increasing lymph node count with standard right hemicolectomy according to nodal status and prognostic outcomes in right-sided tumors. METHODS: Retrospective analysis of prospectively collected clinical data from patients with proximal colonic adenocarcinomas (n = 1390) following right hemicolectomy. Associations between lymph node counts (0-12 vs. 13-15, 16-20, and >20) and recurrence-free survival (RFS) and OS were examined using multivariate Cox modeling adjusted for confounders. RESULTS: We found no association between increasing nodal count and RFS, regardless of nodal status. In the absence of nodal metastases, increasing nodal count (16-20 and >20 vs. 0-12 nodes) was associated with 57% (95% confidence interval [CI]: 0.21-0.89) and 52% (95% CI: 0.24-0.95) improved OS, respectively. In the presence of nodal metastases, increasing nodal count was not associated with OS. Adjuvant chemotherapy did not modify this effect. CONCLUSION: Increasing nodal count (>15 nodes) with right hemicolectomy was not associated with improved RFS. Improved OS was only found for node-negative tumors, casting some doubt on the benefits of resecting more lymph nodes in the presence of nodal metastases.

T-stage downstaging of locally advanced rectal cancer after neoadjuvant chemoradiotherapy is not associated with reduced recurrence after adjusting for tumour characteristics.

BACKGROUND AND OBJECTIVES: Prior studies examining prognostic outcomes of locally advanced rectal adenocarcinomas achieving a complete pathological response following neoadjuvant chemoradiotherapy (nCRT) did not adjust for adverse prognostic factors in multivariate analyses and account for magnetic resonance imaging tumour staging inaccuracy pre-nCRT. We aimed to clarify prognostic outcomes in mT3 rectal adenocarcinomas with ypT-downstaging post-nCRT in robust adjusted analyses. METHODS: Retrospective analysis of prospectively-collected clinical data from 528 mT3 rectal adenocarcinomas ≤12 cm from the anal verge, any N-stage, no metastases, post-nCRT following total mesorectal excision (TME). Recurrence outcomes (local and distant combined) of tumours with complete ypT-downstaging (ypT0) post-nCRT before TME compared with no ypT-downstaging (≥ypT3) were examined using multivariate Cox regression, adjusting for confounders and accounting for pre-nCRT mT3-staging inaccuracy using bootstrapping. RESULTS: Complete ypT-downstaging was achieved in of 17.6% tumours and correlated strongly with complete pathological response. Complete ypT-downstaging was not associated with reduced recurrence hazards compared with no ypT-downstaging (hazard ratio = 0.60; 95% confidence interval [CI]: 0.23-1.56; p = 0.30). Lymphovascular invasion (LVI) and ypN+ve increased recurrence hazards by 1.8-fold (95% CI: 1.10-2.79; p = 0.02) and 2.3-fold (95% CI: 1.48-3.54; p = 0.0002), respectively. CONCLUSION: Complete ypT-downstaging was not associated with reduced recurrence after adjusting for confounders and accounting for mT3-staging inaccuracy, even in the absence of adverse prognostic factors (ypN+, LVI).

Hospital Acquired Infections in Surgical Patients: Impact of COVID-19-Related Infection Prevention Measures.

BACKGROUND: Hospital acquired infections are common, costly, and potentially preventable adverse events. This study aimed to determine the effect of the COVID-19 pandemic-related escalation in infection prevention and control measures on the incidence of hospital acquired infection in surgical patients in a low COVID-19 environment in Australia. METHOD: This was a retrospective cohort study in a tertiary institution. All patients undergoing a surgical procedure from 1 April 2020 to 30 June 2020 (COVID-19 pandemic period) were compared to patients pre-pandemic (1 April 2019-30 June 2019). The primary outcome investigated was odds of overall hospital acquired infection. The secondary outcome was patterns of involved microorganisms. Univariable and multivariable logistic regression analysis was performed to assess odds of hospital acquired infection. RESULTS: There were 5945 admission episodes included in this study, 224 (6.6%) episodes had hospital acquired infections in 2019 and 179 (7.1%) in 2020. Univariable logistic regression analysis demonstrated no evidence of change in odds of having a hospital acquired infection between cohorts (OR 1.08, 95% CI 0.88-1.33, P = 0.434). The multivariable regression analysis adjusting for potentially confounding co-variables also demonstrated no evidence of change in odds of hospital acquired infection (OR 0.93, 95% CI 0.74-1.16, P = 0.530). CONCLUSION: Increased infection prevention and control measures did not affect the incidence of hospital acquired infection in surgical patients in our institution, suggesting that there may be a plateau effect with these measures in a system with a pre-existing high baseline of practice.

Delayed ileostomy closure increases the odds of Clostridium difficile infection.

AIM: A diverting ileostomy is typically performed to divert intestinal contents in high-risk colorectal anastomoses. Ileostomy closure is associated with high rates of postoperative Clostridium difficile infection (CDI). Risk factors for the development of CDI are unclear; however, a correlation has been observed with delayed closure. This study aimed to assess the odds of developing CDI in patients who had a delay to reversal of ileostomy, compared to those who had no delay. METHODS: A retrospective cohort study was conducted of patients undergoing reversal of ileostomy between 2010 and 2019 at a single tertiary centre. A delay to reversal of ileostomy was defined if the procedure was performed at >365 days following the index procedure. CDI was defined as the presence of Clostridium difficile toxin associated with diarrhoea. Univariable logistic regression analysis was performed to estimate odds of CDI for each covariable, comparing patients who had a delay to reversal of ileostomy with those who did not. Multivariable logistic regression analysis was used to adjust for the potential confounding effects of covariables. RESULTS: Of 195 patients, 11 (5.6%), developed postoperative CDI. Multivariable analysis showed that delay to reversal of ileostomy was associated with a nearly 7-fold increase in odds of CDI (OR = 6.95, CI: 1.06-81.6; p-value = 0.03). CONCLUSION: A delay to reversal of ileostomy of >365 days was associated with a higher incidence of CDI postoperatively. Careful consideration should be given to the timing of reversal and appropriate preoperative counselling of patients.

Expanding the genotypic and phenotypic spectrum of severe serine biosynthesis disorders.

Serine biosynthesis disorders comprise a spectrum of very rare autosomal recessive inborn errors of metabolism with wide phenotypic variability. Neu-Laxova syndrome represents the most severe expression and is characterized by multiple congenital anomalies and pre- or perinatal lethality. Here, we present the mutation spectrum and a detailed phenotypic analysis in 15 unrelated families with severe types of serine biosynthesis disorders. We identified likely disease-causing variants in the PHGDH and PSAT1 genes, several of which have not been reported previously. Phenotype analysis and a comprehensive review of the literature corroborates the evidence that serine biosynthesis disorders represent a continuum with varying degrees of phenotypic expression and suggest that even gradual differences at the severe end of the spectrum may be correlated with particular genotypes. We postulate that the individual residual enzyme activity of mutant proteins is the major determinant of the phenotypic variability, but further functional studies are needed to explore effects at the enzyme protein level.

Neoadjuvant Chemoradiotherapy and Tumor Recurrence in Patients with Early T-Stage Cancer of the Lower Rectum.

BACKGROUND: The role neoadjuvant chemoradiotherapy (nCRT) plays in oncological outcomes in early T-stage rectal cancer is uncertain. The present work aims to clarify prognostic outcomes by estimating the effect of nCRT on tumor recurrence prior to major surgery compared with major surgery alone. PATIENTS AND METHODS: Prospectively collected data were retrospectively analyzed for patients diagnosed with localized rectal adenocarcinoma ≤ 8 cm from the anal verge, with final histopathology ≤ T2 (≤ ypT2/≤ pT2), regardless of magnetic resonance imaging staging, between 1990 and 2017. As the effect of nCRT on recurrence varied over time, thereby violating the Cox proportional hazards assumption, the effect of nCRT on recurrence hazards was estimated using a time-varying multivariate Cox model over two separate time intervals (≤ 1 year and > 1 year postsurgery) by nCRT. RESULTS: Long-course nCRT was associated with a 5.6-fold increase in the hazard of recurrence ≤ 1 year postsurgery [hazard ratio (HR) 5.6; 95% confidence interval (CI) 1.2-24.9; P = 0.02], but there was no increase in recurrence hazards > 1 year (HR 0.84; 95% CI 0.4-2.0; P = 0.70). In subgroup analysis restricted to ≤ mrT2/≤ ypT2 and ≤ pT2 tumors (omitting > mrT2 tumors), the effect of nCRT on recurrence no longer varied over time, indicating that tumor heterogeneity was responsible for the observed increased recurrence hazards ≤ 1 year postsurgery; That is, > mrT2 tumors that were downstaged to ≤ ypT2 after nCRT were responsible for the time-varying effects of nCRT and increased recurrence hazards ≤ 1 year postsurgery. Subsequently, no difference was found in prognostic outcomes either with or without nCRT before surgery in the homogeneous population of ≤ mrT2/≤ ypT2 and ≤ pT2 tumors. CONCLUSIONS: No evidence was found to indicate that nCRT prior to surgery reduces tumor recurrence in early T-stage lower rectal cancer compared with surgery alone.

Laparoscopic Compared With Open Resection for Colorectal Cancer and Long-term Incidence of Adhesional Intestinal Obstruction and Incisional Hernia: A Systematic Review and Meta-analysis.

BACKGROUND: Incisional hernia and adhesional intestinal obstruction are important complications of laparoscopic and open resection for colorectal cancer. This is the largest systematic review of comparative studies on this topic. OBJECTIVE: This study aimed to investigate whether laparoscopic surgery decreases the incidence of incisional hernia and adhesional intestinal obstruction compared to open surgery for colorectal cancer. DATA SOURCES: Online databases PubMed, EMBASE, and the Cochrane Library were searched. Abstracts from the annual meetings of the American Society of Colon and Rectal Surgeons and the European Society of Coloproctology were performed to cover gray literature. STUDY SELECTION: We included both randomized and nonrandomized comparative studies. INTERVENTIONS: Laparoscopic resection was compared to open resection for patients with colorectal cancer. MAIN OUTCOMES MEASURES: The primary outcomes measured were incisional hernia and adhesional intestinal obstruction. RESULTS: Fifteen studies met inclusion criteria (6 randomized comparative studies/9 nonrandomized comparative studies); 84,172 patients. Meta-analysis showed decreased odds of developing incisional hernia in the laparoscopic cohort (OR, 0.79; 95% CI, 0.66-0.95; p = 0.01) but no difference in requirement for surgery (OR, 1.07; 95% CI, 0.64-1.79; p = 0.79). Similarly, there were decreased odds of developing adhesional intestinal obstruction in the laparoscopic cohort (OR, 0.81; 95% CI, 0.72-0.92, p = 0.001), but no difference in requirement for surgery (OR, 0.84; 95% CI, 0.53-1.35; p = 0.48). LIMITATIONS: Incisional hernia and adhesional intestinal obstruction were poorly defined in many studies. CONCLUSION: Laparoscopic surgery is associated with decreased odds of incisional hernias and adhesional intestinal obstructions compared with open surgery for colorectal cancer.

A craniosynostosis massively parallel sequencing panel study in 309 Australian and New Zealand patients: findings and recommendations.

PURPOSE: The craniosynostoses are characterized by premature fusion of one or more cranial sutures. The relative contribution of previously reported genes to craniosynostosis in large cohorts is unclear. Here we report on the use of a massively parallel sequencing panel in individuals with craniosynostosis without a prior molecular diagnosis. METHODS: A 20-gene panel was designed based on the genes' association with craniosynostosis, and clinically validated through retrospective testing of an Australian and New Zealand cohort of 233 individuals with craniosynostosis in whom previous testing had not identified a causative variant within FGFR1-3 hot-spot regions or the TWIST1 gene. An additional 76 individuals were tested prospectively. RESULTS: Pathogenic or likely pathogenic variants in non-FGFR genes were identified in 43 individuals, with diagnostic yields of 14% and 15% in retrospective and prospective cohorts, respectively. Variants were identified most frequently in TCF12 (N = 22) and EFNB1 (N = 8), typically in individuals with nonsyndromic coronal craniosynostosis or TWIST1-negative clinically suspected Saethre-Chotzen syndrome. Clinically significant variants were also identified in ALX4, EFNA4, ERF, and FGF10. CONCLUSION: These findings support the clinical utility of a massively parallel sequencing panel for craniosynostosis. TCF12 and EFNB1 should be included in genetic testing for nonsyndromic coronal craniosynostosis or clinically suspected Saethre-Chotzen syndrome.

Magnetoresistance Scaling Reveals Symmetries of the Strongly Correlated Dynamics in BaFe_{2}(As_{1-x}P_{x})_{2}.

The phenomenon of T-linear resistivity commonly observed in a number of strange metals has been widely seen as evidence for the breakdown of the quasiparticle picture of metals. This study shows that a recently discovered H/T scaling relationship in the magnetoresistance of the strange metal BaFe_{2}(As_{1-x}P_{x})_{2} is independent of the relative orientations of current and magnetic field. Rather, its magnitude and form depend only on the orientation of the magnetic field with respect to a single crystallographic axis: the direction perpendicular to the magnetic iron layers. This finding suggests that the magnetotransport scaling does not originate from the conventional averaging or orbital velocity of quasiparticles as they traverse a Fermi surface, but rather from dissipation arising from two-dimensional correlations.

Imaging Anomalous Nematic Order and Strain in Optimally Doped BaFe_{2}(As,P)_{2}.

We present the strain and temperature dependence of an anomalous nematic phase in optimally doped BaFe_{2}(As,P)_{2}. Polarized ultrafast optical measurements reveal broken fourfold rotational symmetry in a temperature range above T_{c} in which bulk probes do not detect a phase transition. Using ultrafast microscopy, we find that the magnitude and sign of this nematicity vary on a 50-100 µm length scale, and the temperature at which it onsets ranges from 40 K near a domain boundary to 60 K deep within a domain. Scanning Laue microdiffraction maps of local strain at room temperature indicate that the nematic order appears most strongly in regions of weak, isotropic strain. These results indicate that nematic order arises in a genuine phase transition rather than by enhancement of local anisotropy by a strong nematic susceptibility. We interpret our results in the context of a proposed surface nematic phase.

International Variation in Emergency Operation Rates for Acute Diverticulitis: Insights into Healthcare Value.

BACKGROUND: International comparison of outcomes of surgical diseases has become a global focus because of widespread concern over surgical quality, rising costs and the value of healthcare. Acute diverticulitis is a common disease potentially amenable to optimization of strategies for operative intervention. The aim was to compare the emergency operative intervention rates for acute diverticulitis in USA, England and Australia. METHODS: Unplanned admissions for acute diverticulitis were found from an international administrative dataset between 2008 and 2014 for hospitals in USA, England and Australia. The primary outcome measured was emergency operative intervention rate. Secondary outcomes included inpatient mortality and percutaneous drainage rate. Multivariable analysis was performed after development of a weighted comorbidity scoring system. RESULTS: There were 15,150 unplanned admissions for acute diverticulitis. The emergency operative intervention rates were 16, 13 and 10% for USA, England and Australia. The percutaneous drainage rate was highest in USA at 10%, while the mortality rate was highest in England at 2.8%. The propensity for emergency operative intervention was higher in USA (OR 1.45, p < 0.001) and England (OR 1.49, p < 0.001) than in Australia. The risk of 7-day mortality was higher in England than in Australia (OR 2.79, p < 0.001). Percutaneous drainage was associated with reduced 7-day mortality risk. CONCLUSION: Australia has a lower propensity for emergency operative intervention, while England has a greater risk of mortality for acute diverticulitis. International variations raise the issue of healthcare value in terms of differing resource use and outcomes.

Clinical and genetic aspects of KBG syndrome.

KBG syndrome is characterized by short stature, distinctive facial features, and developmental/cognitive delay and is caused by mutations in ANKRD11, one of the ankyrin repeat-containing cofactors. We describe 32 KBG patients aged 2-47 years from 27 families ascertained via two pathways: targeted ANKRD11 sequencing (TS) in a group who had a clinical diagnosis of KBG and whole exome sequencing (ES) in a second group in whom the diagnosis was unknown. Speech delay and learning difficulties were almost universal and variable behavioral problems frequent. Macrodontia of permanent upper central incisors was seen in 85%. Other clinical features included short stature, conductive hearing loss, recurrent middle ear infection, palatal abnormalities, and feeding difficulties. We recognized a new feature of a wide anterior fontanelle with delayed closure in 22%. The subtle facial features of KBG syndrome were recognizable in half the patients. We identified 20 ANKRD11 mutations (18 novel: all truncating) confirmed by Sanger sequencing in 32 patients. Comparison of the two ascertainment groups demonstrated that facial/other typical features were more subtle in the ES group. There were no conclusive phenotype-genotype correlations. Our findings suggest that mutation of ANKRD11 is a common Mendelian cause of developmental delay. Affected patients may not show the characteristic KBG phenotype and the diagnosis is therefore easily missed. We propose updated diagnostic criteria/clinical recommendations for KBG syndrome and suggest that inclusion of ANKRD11 will increase the utility of gene panels designed to investigate developmental delay. © 2016 The Authors. American Journal of Medical Genetics Part A Published by Wiley Periodicals, Inc.

Total caseload of a colorectal surgical unit: baseline measurement and identification of areas for efficiency gains.

PURPOSE: Resource limitations are a concern in most modern public hospital systems. The aim of this study is to prospectively quantify the total caseload of a tertiary colorectal surgery unit to identify areas of redundancy. METHODS: Data was collected prospectively at all points of clinical care (outpatient clinic, inpatient referrals, operating theatre and endoscopy) between March 2014 and March 2015 using specifically designed templates. The final data was analysed using descriptive statistics. RESULTS: During the study period, 4012 patient episodes were recorded: 2871 in outpatient clinic, 186 as emergency patient referrals, 541 at colonoscopy and 414 at surgery. The largest component of the caseload was made up primarily of colonoscopy results follow-up, protocol review for previous cancer or polyps and post-operative review. Sixty-eight percent of these episodes did not result in any active intervention such as further tests or surgery. Most new outpatient referrals were undifferentiated, with the most common indications being minor rectal bleeding, non-specific gastrointestinal symptoms, and minor non-bleeding anorectal problems. Of the new referrals, 56 % were booked for a colonoscopy, and only 13.3 % were booked directly for elective surgery. CONCLUSION: A large component of the caseload of a tertiary colorectal surgery unit is made up of post-colonoscopy, post-operative, and surveillance protocol follow-up, with a significant proportion of patients not requiring any active intervention. The majority of new referrals are undifferentiated and result in a low rate of direct booking for operative intervention. Rationalisation of this resource using evidence-based methods could reduce redundancy, workload, and cost.