MCM9 Is Required for Mammalian DNA Mismatch Repair.

DNA mismatch repair (MMR) is an evolutionarily conserved process that corrects DNA polymerase errors during replication to maintain genomic integrity. In E. coli, the DNA helicase UvrD is implicated in MMR, yet an analogous helicase activity has not been identified in eukaryotes. Here, we show that mammalian MCM9, a protein involved in replication and homologous recombination, forms a complex with MMR initiation proteins (MSH2, MSH3, MLH1, PMS1, and the clamp loader RFC) and is essential for MMR. Mcm9-/- cells display microsatellite instability and MMR deficiency. The MCM9 complex has a helicase activity that is required for efficient MMR since wild-type but not helicase-dead MCM9 restores MMR activity in Mcm9-/- cells. Moreover, MCM9 loading onto chromatin is MSH2-dependent, and in turn MCM9 stimulates the recruitment of MLH1 to chromatin. Our results reveal a role for MCM9 and its helicase activity in mammalian MMR.

Using Machine Learning to Predict Remission in Patients With Major Depressive Disorder Treated With Desvenlafaxine.

BACKGROUND: Major depressive disorder (MDD) is a common and burdensome condition that has low rates of treatment success for each individual treatment. This means that many patients require several medication switches to achieve remission; selecting an effective antidepressant is typically a sequential trial-and-error process. Machine learning techniques may be able to learn models that can predict whether a specific patient will respond to a given treatment, before it is administered. This study uses baseline clinical data to create a machine-learned model that accurately predicts remission status for a patient after desvenlafaxine (DVS) treatment. METHODS: We applied machine learning algorithms to data from 3,399 MDD patients (90% of the 3,776 subjects in 11 phase-III/IV clinical trials, each described using 92 features), to produce a model that uses 26 of these features to predict symptom remission, defined as an 8-week Hamilton Depression Rating Scale score of 7 or below. We evaluated that learned model on the remaining held-out 10% of the data (n = 377). RESULTS: Our resulting classifier, a trained linear support vector machine, had a holdout set accuracy of 69.0%, significantly greater than the probability of classifying a patient correctly by chance. We demonstrate that this learning process is stable by repeatedly sampling part of the training dataset and running the learner on this sample, then evaluating the learned model on the held-out instances of the training set; these runs had an average accuracy of 67.0% ± 1.8%. CONCLUSIONS: Our model, based on 26 clinical features, proved sufficient to predict DVS remission significantly better than chance. This may allow more accurate use of DVS without waiting 8 weeks to determine treatment outcome, and may serve as a first step toward changing psychiatric care by incorporating clinical assistive technologies using machine-learned models.

St Georg Sled medial unicompartmental arthroplasty: survivorship analysis and function at 20 years follow up.

PURPOSE: The peri-operative and short-term benefits of unicompartmental knee arthroplasty (UKA) are well supported in the literature. However, there remains concern regarding the higher revision rate when compared with total knee replacement. This manuscript reports the functional outcome and survivorship of a large series of fixed bearing, medial unicompartmental replacements (St Georg Sled), with a minimum of 20 years follow-up. METHODS: Between 1974 and 1994, 399 patients (496 knees) underwent a medial fixed-bearing UKA. Prospective data were collected pre-operatively and at regular intervals post-operatively using the Bristol Knee Score (BKS), Oxford Knee (OKS) and Western Ontario MacMaster (WOMAC) scores. Kaplan-Meier survival analysis was used to determine survivorship, with revision or need for revision as end point, and differences assessed using Mantel-Cox log rank test. RESULTS: Functional knee scores improved post-operatively, but demonstrated a slight decline from 10 years of follow-up onwards. Survivorship is estimated as 86% at 10 years, 80% at 15 years, and 78% at 20 years. Sixty knees were revised, with progression of disease in another compartment the commonest reason. Eighty eight percent were revised using a primary prosthesis. For patients over the age of 65 years at the time of index procedure, 93% died with a functioning prosthesis in situ. CONCLUSION: Medial UKA demonstrates good long-term function and survivorship, and represents an excellent surgical option for patients aged over 65 years of age, where few patients will require a revision procedure. LEVEL OF EVIDENCE: IV.

The association between bacterobilia and the risk of postoperative complications following pancreaticoduodenectomy.

BACKGROUND: Pre-operative biliary bacterial colonisation (bacterobilia) is considered a risk factor for infectious complications after pancreaticoduodenectomy (PD). This study aimed to investigate the role of the PD biliary microbiome grown in the development of post-PD complications. METHODS: In a retrospective study of 162 consecutive patients undergoing PD (2008-2018), intra-operative bile cultures were analyzed and sensitivities compared to pre-anesthetic antibiotics and thirty-day post-surgery complications. RESULTS: Bacterobilia was present in 136 patients (84%). Most bile cultures grew bacteria resistant to pre-operative antibiotics (n = 112, 82%). Patients with bacterobilia had significantly higher rates of major complication than patients without (P = 0.017), as well as higher rates of surgical-site infections (SSI) (P = 0.010). Patients with negative bile cultures (n = 26) had significantly lower rates of major complication and SSI than those growing sensitive (n = 24) or non-sensitive (n = 112) bacteria (major complication P = 0.029 and SSI P = 0.011). CONCLUSION: Positive bile cultures were associated with a higher incidence of major complications and SSI. Patients with sterile bile cultures had the lowest risk of post-operative complications and efforts to reduce rates of bacterobilia, such as limitation of biliary instrumentation, should be considered. Sensitivity to antibiotics had no effect upon the rate of post-operative complications, but this may reflect low cohort numbers.

COVID-19 and food systems in Pacific Island Countries, Papua New Guinea, and Timor-Leste: Opportunities for actions towards the sustainable development goals.

Context: The COVID-19 pandemic has impacted global food systems. This has led to different strategies by communities, governments, and businesses involved in food systems to mitigate and adapt to the unfolding pandemic. Small Island Developing States are particularly exposed to the conflation of risks from COVID-19 disease, economic downturns, underlying climate vulnerabilities and biosecurity risks. Objective: Our study aimed to identify the food systems vulnerabilities, impacts, and opportunities for supporting resilience and sustainable development in selected Pacific Island countries, Papua New Guinea, and Timor-Leste. The study focused on the impacts from the first six months of the pandemic (February-July 2020), with remote data collection and analysis done between May and July 2020. Methods: We conducted 67 interviews, and triangulated information with desktop and news sources emerging at the time. We present results on the effect on smallholder livelihoods, supply chains, governance, communities and employment. Overall, the major impacts of COVID-19 have been on economies, posing risks to future food security and further hampering progress towards key Sustainable Development Goals. Results and conclusions: We found that unemployment and economic contraction have been the most severe effects to date, with long-term consequences for food value chains and smallholder farmers. Disruptions to tourism, labour migration, and remittances have led to varying socio-economic impacts throughout the region. Vulnerable groups, notably women, urban poor, and youth, have been disproportionately affected by unemployment. Timor-Leste has had some social protection measures, whereas in Pacific Countries these have been varied. The lockdowns and State of Emergency initially influenced the distribution and marketing of food, but local food economies are starting to stabilise. The continued functioning of international food supply chains reduced the risk of food insecurity in high import dependent nations, notably import dependent countries like Tuvalu and Kiribati. Significance: The results have significance for three recovery pathways. The first recovery pathway relates to revisiting value chains in light of restricted travel. The second recovery pathway exists through leveraging the adaptive capacities of communities to stimulate innovative agriculture that also integrates climate adaptation and nutrition. The third recovery pathway relates to addressing the structural challenges that perpetuate inequalities and poverty while finding new ways of implementing inclusive policies and research. Our study presents a set of comparative examples of managing a food system shock that can inform future systems-oriented research and policy for sustainable development.

A rapid assessment framework for food system shocks: Lessons learned from COVID-19 in the Indo-Pacific region.

The frequency and severity of shocks to food systems is accelerating globally, exemplified by the current COVID-19 outbreak. In low- and middle-income countries, the impacts have exacerbated existing food system vulnerabilities and poverty. Governments and donors must respond quickly, but few tools are available that identify interventions to build food system resilience, or emerging opportunities for transformation. In this paper we reflect on the application of a systems-based rapid assessment which we applied across 11 Indo-Pacific countries in May-July 2020. Our approach was shaped by three design parameters: the integration of key informants' perspectives engaged remotely within the countries, applicability to diverse food systems and COVID-19 experiences across the region, and the consideration of food systems as complex systems. For the rapid assessment we adopted an analytical framework proposed by Allen and Prosperi (2016). To include a development lens, we added the analysis of vulnerable groups and their exposure, impacts, recovery potential and resilience, and pro-poor interventions. We concluded that the framework and approach facilitated integration and triangulation of disparate knowledge types and data to identify priority interventions and was sufficiently flexible to be applied across food systems, at both national, sub-national and commodity scales. The step-wise method was simple and enabled structured inquiry and reporting. Although the systems concepts appeared more easily transferrable to key informants in some countries than others, potentially transformational interventions were identified, and also some risks of maladaptation. We present a refined framework that emphasises analysis of political, economic and institutional drivers of exposure and vulnerability, the constraints that they pose for building recovery potential and resilience, and trade-offs amongst winners and losers inherent in proposed interventions.

Scavenging in the Anthropocene: Human impact drives vertebrate scavenger species richness at a global scale.

Understanding the distribution of biodiversity across the Earth is one of the most challenging questions in biology. Much research has been directed at explaining the species latitudinal pattern showing that communities are richer in tropical areas; however, despite decades of research, a general consensus has not yet emerged. In addition, global biodiversity patterns are being rapidly altered by human activities. Here, we aim to describe large-scale patterns of species richness and diversity in terrestrial vertebrate scavenger (carrion-consuming) assemblages, which provide key ecosystem functions and services. We used a worldwide dataset comprising 43 sites, where vertebrate scavenger assemblages were identified using 2,485 carcasses monitored between 1991 and 2018. First, we evaluated how scavenger richness (number of species) and diversity (Shannon diversity index) varied among seasons (cold vs. warm, wet vs. dry). Then, we studied the potential effects of human impact and a set of macroecological variables related to climatic conditions on the scavenger assemblages. Vertebrate scavenger richness ranged from species-poor to species rich assemblages (4-30 species). Both scavenger richness and diversity also showed some seasonal variation. However, in general, climatic variables did not drive latitudinal patterns, as scavenger richness and diversity were not affected by temperature or rainfall. Rainfall seasonality slightly increased the number of species in the community, but its effect was weak. Instead, the human impact index included in our study was the main predictor of scavenger richness. Scavenger assemblages in highly human-impacted areas sustained the smallest number of scavenger species, suggesting human activity may be overriding other macroecological processes in shaping scavenger communities. Our results highlight the effect of human impact at a global scale. As species-rich assemblages tend to be more functional, we warn about possible reductions in ecosystem functions and the services provided by scavengers in human-dominated landscapes in the Anthropocene.

Extracting order from heterogeneity: A report on the EpiGeneSys workshop "Single Cell Epigenetics" in Montpellier, June 11-12, 2015.

Understanding epigenetic modifications to chromatin that regulate gene expression and cell-fate decisions is now possible in single cells thanks to recent technological advances. As interdisciplinary approaches are required to derive biological principles, this workshop brought together some of Europe's leading researchers in single-cell epigenetics to share technologies and biological insights.

Towards appropriate mainstreaming of "Theory of Change" approaches into agricultural research for development: Challenges and opportunities.

Food insecurity persists in many parts of Africa and Asia, despite ongoing agricultural research for development (AR4D) interventions. This is resulting in a growing demand for alternative approaches to designing and evaluating interventions in complex systems. Theory of Change (ToC) is an approach which may be useful because it enables stakeholders to present and test their theories and assumptions about why and how impact may occur, ideally within an environment conducive to iterative reflection and learning. However, ToC is yet to be appropriately mainstreamed into development by donors, researchers and practitioners. We carried out a literature review, triangulated by interviews with 26 experts in African and Asian food security, consisting of researchers, advisors to programs, and donors. Although 17 (65%) of the experts had adopted ToC, their responses and the literature revealed four challenges to mainstreaming: (i) different interpretations of ToC; (ii) incoherence in relationships among the constituent concepts of ToC; (iii) confused relationships between ToC and project "logframes"; and (iv) limitations in necessary skills and commitment for enacting ToC. A case study of the evolution of a ToC in a West African AR4D project over 4 years which exemplified these challenges is presented. Five recommendations arise to assist the mainstreaming of ToC: (i) select a type of ToC suited to the relative complexity of the problem and focal system of interest; (ii) state a theory or hypotheses to be tested as the intervention progresses; (iii) articulate the relationship between the ToC and parallel approaches (e.g. logframe); (iv) accept that a ToC is a process, and (v) allow time and resources for implementers and researchers to develop ToC thinking within projects. Finally, we suggest that communities of practice should be established among AR4D and donor organisations to test, evaluate and improve the contribution that ToCs can make to sustainable food security and agricultural development.

Community motivations to engage in conservation behavior to conserve the Sumatran orangutan.

Community-based conservation programs in developing countries are often based on the assumption that heteronomous motivation (e.g., extrinsic incentives such as economic rewards and pressure or coercion to act) will incite local communities to adopt conservation behaviors. However, this may not be as effective or sustainable as autonomous motivations (e.g., an intrinsic desire to act due to inherent enjoyment or self-identification with a behavior and through freedom of choice). We analyzed the comparative effectiveness of heteronomous versus autonomous approaches to community-based conservation programs through a case study of Sumatran orangutan (Pongo abelii) conservation in 3 villages in Indonesia. Each village had a different conservation program design. We surveyed people (n = 240) to determine their motivations for and behavior changes relative to orangutan and orangutan habitat (forest) protection. Heteronomous motivations (e.g., income from tourism) led to greater self-reporting of behavior change toward orangutan protection. However, they did not change self-reported behavior toward forest (i.e., orangutan habitat) protection. The most effective approach to creating self-reported behavior change throughout the community was a combination of autonomous and heteronomous motivations. Individuals who were heteronomously motivated to protect the orangutan were more likely to have changed attitudes than to have changed their self-reported behavior. These findings demonstrate that the current paradigm of motivating communities in developing countries to adopt conservation behaviors primarily through monetary incentives and rewards should consider integrating autonomous motivational techniques that promote the intrinsic values of conservation. Such a combination has a greater potential to achieve sustainable and cost-effective conservation outcomes. Our results highlight the importance of using in-depth sociopsychological analyses to inform the design and implementation of community-based conservation programs.

Does immediate elbow mobilization after distal biceps tendon repair carry the risk of wound breakdown, failure of repair, or patient dissatisfaction?

BACKGROUND: Rehabilitation protocols after distal biceps repair are highly variable, with many surgeons favoring at least 2 weeks of immobilization. Is this conservative approach necessary to protect the repair? METHODS: This was a consecutive series of 22 distal biceps tendon repairs in which a cortical button system was used. Patients were encouraged to mobilize their elbow actively from the day of surgery. Physiotherapy commenced at 3 weeks, with strengthening exercises when full range of movement (ROM) was achieved. The primary outcome measured was the clinical integrity of the repaired tendon. Secondary outcomes comprised wound or nerve complication, elbow ROM, and patient-reported outcome measures (the 11-item version of the Disabilities of Arm, Shoulder and Hand, Mayo Elbow Performance Index, and Oxford Elbow Score). RESULTS: All patients were male, and the dominant arm was repaired in 60%. Mean age was 40.6 years (range, 27-62 years), and mean time to surgery was 17 days (range, 5-99 days). Mean follow-up was 16.6 months (range, 3.8-29 months). All tendons were clinically intact at time of review. No wound breakdown occurred. Mean extension was -6° (range, -10° to 10°), and flexion was 144° (range, 135°-150°). All patients achieved full pronosupination. ROM was equivalent to the uninjured arm (P = .7). The mean 11-item version of the Disabilities of Arm, Shoulder and Hand score was 2.7 (range, 0-15.9), the Mayo Elbow Performance Index was 97.8 (range, 70-100), and the Oxford Elbow Score was 46.9 (range, 43-48) at the latest follow-up. One-third of patients experienced a transient sensory neurapraxia. CONCLUSION: Immediate mobilization after biceps tendon repair with a cortical button is possible, and in this series was not associated with failure of the repair, wound breakdown, or patient dissatisfaction. However, this series emphasizes the high incidence of nerve complication that can be associated with the single transverse incision technique.

The effect of renin angiotensin system genetic variants in acute pancreatitis.

OBJECTIVES: We sought association of genetic variants in the renin-angiotensin system (RAS) and vitamin D system with acute pancreatitis (AP) development and severity. BACKGROUND: The endocrine RAS is involved in circulatory homeostasis through the pressor action of angiotensin II at its AT1 receptor. However, local RAS regulate growth and inflammation in diverse cells and tissues, and their activity may be suppressed by vitamin D. Intrapancreatic angiotensin II generation has been implicated in the development of AP. METHODS: Five hundred forty-four white patients with AP from 3 countries (United Kingdom, 22; Germany, 136; and The Netherlands 386) and 8487 control subjects (United Kingdom 7833, The Netherlands 717) were genotyped for 8 polymorphisms of the RAS/vitamin D systems, chosen on the basis of likely functionality. RESULTS: The angiotensin-converting enzyme I (rather than D) allele was significantly associated with alcohol-related AP when all cohorts were combined (P = 0.03). The renin rs5707 G (rather than A) allele was associated with AP (P = 0.002), infected necrosis (P = 0.025) and mortality (P = 0.046). CONCLUSIONS: The association of 2 RAS polymorphisms with AP suggests the need for further detailed analysis of the role of RAS/vitamin D in the genesis or severity of AP, particularly given the ready potential for pharmacological manipulation of this system using existing marketed agents. However, further replication studies will be required before any such association is considered robust, particularly given the significant heterogeneity of AP causation and clinical course.

The role of colonoscopic screening in acromegaly revisited: review of current literature and practice guidelines.

INTRODUCTION: Acromegaly is a chronic, debilitating and disfiguring condition with a significantly increased morbidity and mortality due to cardiovascular, as well as respiratory complications. Patients with acromegaly are usually diagnosed at the age of 40, however, the duration of symptoms can vary from 5 to 10 years before the formal diagnosis is confirmed. Recent advances in the field of acromegaly have improved survival significantly. A strong association between acromegaly and premalignant colonic lesions and colon cancer has been highlighted. Furthermore, patients with acromegaly have a greater lifetime risk of malignant transformation and a far worse overall prognosis from colorectal cancer, which is now considered a major disease related complication. MATERIALS AND METHODS: A comprehensive search strategy was applied for the Medline/PubMed electronic database from its inception until April 2014. We considered all human research articles published in English, not classified as case report, editorial, comment, letter, or news. CONCLUSION: Specific recommendations for large bowel endoscopic screening in patients with acromegaly have been proposed. In this comprehensive review we discuss the current state of knowledge and evidence on colonoscopic screening in patients with acromegaly illustrated by a case of aggressive colorectal cancer presenting late in a young woman with difficult to control acromegaly.

Studying Translesion DNA Synthesis Using Xenopus In Vitro Systems.

Cell-free extracts derived from Xenopus eggs have been widely used to decipher molecular pathways involved in several cellular processes including DNA synthesis, the DNA damage response, and genome integrity maintenance. We set out assays using Xenopus cell-free extracts to study translesion DNA synthesis (TLS), a branch of the DNA damage tolerance pathway that allows replication of damaged DNA. Using this system, we were able to recapitulate TLS activities that occur naturally in vivo during early embryogenesis. This chapter describes protocols to detect chromatin-bound TLS factors by western blotting and immunofluorescence microscopy upon induction of DNA damage by UV irradiation, monitor TLS-dependent mutagenesis, and perform proteomic screening.

Bridging evidence-to-care gaps with mHealth: Designing a symptom checker for parents accessing knowledge translation resources on acute children's illnesses in a smartphone application.

Background: Smartphone applications offer a novel platform for delivering health information to parents. This study created and evaluated an app-based symptom checker that recommends educational tools to parents based on their child's symptoms. Methods: Symptoms extracted from 23 knowledge translation (KT) tools for 10 children's illnesses comprised a set of plain-language symptoms. The symptom checker works by producing confusion matrices evaluating a child's reported symptoms against possible illnesses, comparing precision scores to examine how well each illness matched reported symptoms, and ordering possible illnesses by performance score. Performance was evaluated by extracting symptoms from 8 clinical vignettes, and examining correct first-try matches. Results: We created a final list of 54 plain-language symptoms. Visualizations of the symptom set creation process and logic mapping are presented, as well as images of the working symptom checker. The symptom checker matched 100% (8/8) of tested clinical vignettes to the appropriate illness resource. Discussion: Symptom checkers are a potentially useful tool to integrate into apps that parents use for their children's health. The design of these systems has the potential to change parents' relationship with technology, affecting both their adoption and acceptance of symptom checkers. Our design choices contribute to addressing current barriers to the adoption of symptom checkers, reducing functional, critical, and interactive literacy requirements for parents.

Microtubule assembly by the Apc protein is regulated by importin-beta--RanGTP.

Mutations in the tumour suppressor Adenomatous polyposis coli (Apc) initiate most sporadic colorectal cancers. Apc is implicated in regulating microtubule (MT) dynamics in interphase and mitosis. However, little is known about the underlying mechanism or regulation of this Apc function. We identified importin-beta as a binding partner of Apc that regulates its effect on MTs. Apc binds importin-beta in vitro and in Xenopus egg extracts, and RanGTP inhibits this interaction. The armadillo-like repeat domain of importin-beta binds to the middle of Apc, where it can compete with beta-catenin. In addition, two independent sites in the C terminus of Apc bind the N-terminal region of importin-beta. Binding to importin-beta reduces the ability of Apc to assemble and bundle MTs in vitro and to promote assembly of microtubule asters in Xenopus egg extracts, but does not affect the binding of Apc to MTs or to EB1. Depletion of Apc decreases the formation of cold-stable spindles in Xenopus egg extracts. Importantly, the ability of purified Apc to rescue this phenotype was reduced when it was constitutively bound to importin-beta. Thus, importin-beta binds to Apc and negatively regulates the MT-assembly and spindle-promoting activity of Apc in a Ran-regulatable manner.

An observational study to determine the effect of delayed admission to the intensive care unit on patient outcome.

INTRODUCTION: Delayed patient admission to the intensive care unit (ICU) due to lack of bed availability is a common problem, but the effect on patient outcome is not fully known. METHODS: A retrospective study was performed using departmental computerised records to determine the effect of delayed ICU admission and temporary management within the operating theatre suite on patient outcome. Emergency surgical and medical patients admitted to the ICU (2003 to 2007) were divided into delay (more than three hours from referral to admission) and no-delay (three or fewer hours from referral to admission) groups. Our primary outcome measure was length of ICU stay. Secondary outcome measures were mortality rates and duration of organ support. RESULTS: A total of 1,609 eligible patients were included and 149 (9.3%) had a delayed admission. The delay and no-delay groups had similar baseline characteristics. Median ICU stay was 5.1 days (delay) and 4.5 days (no-delay) (P = 0.55) and ICU mortality was 26.8% (delay) and 24.2% (no-delay) (P = 0.47). Following adjustment for demographic and baseline characteristics there was no difference in either length of ICU stay or mortality rates between groups. ICU admission delay was associated with both an increased requirement for advanced respiratory support (92.3% delay vs. 76.4% no-delay, P <0.01) and a longer time spent ventilated (median four days delay vs. three days no-delay, P = 0.04). CONCLUSIONS: No significant difference in length of ICU stay or mortality rate was demonstrated between the delay and no-delay cohorts. Patients within the delay group had a significantly greater requirement for advanced respiratory support and spent a longer time ventilated.

Rare presentation of Brunner's gland adenoma: another differentiation in patients with recurrent "idiopathic" pancreatitis.

BACKGROUND: Brunner's gland adenoma (BGA) is an unusual benign neoplasm arising from Brunner's glands in the duodenum. When symptomatic it presents either with duodenal obstruction or bleeding. However, pancreatitis secondary to ampullary obstruction from a BGA is very rare. METHODS: A 23-year-old female presented with recurrent episodes of "idiopathic" pancreatitis. She was extensively investigated and was found to have a large polypoid BGA, intermittently obstructing the ampulla. This created a ball-valve effect causing secondary intermittent obstruction of the pancreatic duct resulting in pancreatitis. The condition was cured surgically, through transduodenal excision of the BGA. We reviewed the surgical literature pertaining to these unusual and similar causes of obstructive pancreatitis, not related to gallstones. RESULTS: BGA of the duodenum is a rare cause of pancreatitis. Extensive investigations should be carried out in all cases of unexplained pancreatitis before classifying the condition as "idiopathic". Discovery of a lesion of this nature gives an opportunity to provide a permanent surgical cure. CONCLUSIONS: BGA adds an unusual etiology for pancreatitis. All patients with pancreatitis should undergo extensive investigations before being termed "idiopathic". Surgical excision of the BGA provides a definitive curative treatment for the adenoma and pancreatitis.

The role of 18FDG PET/CT in the management of colorectal liver metastases.

INTRODUCTION: Surgical resection remains the only potentially curative treatment for colorectal liver metastases (CLM). However, involvement of both the hepatic lobes or extrahepatic disease (EHD) can be a contra-indication for resection. The aim of the present study was to examine the addition of combined positron emission and computed tomography (PET/CT) to CLM staging to assess the effects upon staging and management. METHODS: All CLM patients referred to a single centre between January 2005 and January 2009 were prospectively included. All underwent routine staging (clinical examination and computed tomography), followed by a whole body (18) fluoro-deoxy-glucose ((18)FDG)-PET/CT scan and Fong clinical risk score calculation. RESULTS: Sixty-four patients were included [63% male with a median age of 63 years (age range 32-79 years)]. The addition of PET/CT led to disease upstaging in 20 patients (31%) and downstaging in two patients (3%). EHD was found in 24% of low-risk patients (Fong score 0-2) as compared with 44% of high-risk patients (Fong score 3-5) (P= 0.133). There was a trend towards a greater influence upon management in patients with a low score (44% vs. 17%; P= 0.080). CONCLUSION: The addition of PET/CT led to management changes in over one-third of patients but there was no correlation between alterations in staging or management and the Fong clinical risk score; suggesting that PET/CT should be utilized, where available, in the pre-operative staging of CLM patients.