Tumour budding as a prognostic biomarker in biopsies and resections of neoadjuvant-treated rectal adenocarcinoma.

BACKGROUND: Tumour budding (TB) is a marker of tumour aggressiveness which, when measured in rectal cancer resection specimens, predicts worse outcomes and response to neoadjuvant therapy. We investigated the utility of TB assessment in the setting of neoadjuvant treatment. METHODS AND RESULTS: A single-centre, retrospective cohort study was conducted. TB was assessed using the hot-spot International Tumour Budding Consortium (ITBCC) method and classified by the revised ITBCC criteria. Haematoxylin and eosin (H&E) and AE1/AE3 cytokeratin (CK) stains for ITB (intratumoural budding) in biopsies with PTB (peritumoural budding) and ITB (intratumoural budding) in resection specimens were compared. Logistic regression assessed budding as predictors of lymph node metastasis (LNM). Cox regression and Kaplan-Meier analyses investigated their utility as a predictor of disease-free (DFS) and overall (OS) survival. A total of 146 patients were included; 91 were male (62.3%). Thirty-seven cases (25.3%) had ITB on H&E and 79 (54.1%) had ITB on CK assessment of biopsy tissue. In univariable analysis, H&E ITB [odds (OR) = 2.709, 95% confidence interval (CI) = 1.261-5.822, P = 0.011] and CK ITB (OR = 2.165, 95% CI = 1.076-4.357, P = 0.030) predicted LNM. Biopsy-assessed H&E ITB (OR = 2.749, 95% CI = 1.258-6.528, P = 0.022) was an independent predictor of LNM. In Kaplan-Meier analysis, ITB identified on biopsy was associated with worse OS (H&E, P = 0.003, CK: P = 0.009) and DFS (H&E, P = 0.012; CK, P = 0.045). In resection specimens, CK PTB was associated with worse OS (P = 0.047), and both CK PTB and ITB with worse DFS (PTB, P = 0.014; ITB: P = 0.019). In multivariable analysis H&E ITB predicted OS (HR = 2.930, 95% CI = 1.261-6.809) and DFS (HR = 2.072, 95% CI = 1.031-4.164). CK PTB grading on resection also independently predicted OS (HR = 3.417, 95% CI = 1.45-8.053, P = 0.005). CONCLUSION: Assessment of TB using H&E and CK may be feasible in rectal cancer biopsy and post-neoadjuvant therapy-treated resection specimens and is associated with LNM and worse survival outcomes. Future management strategies for rectal cancer might be tailored to incorporate these findings.

Comprehensive Geriatric Assessment in the Emergency Department: A Prospective Cohort Study of Process, Clinical, and Patient-Reported Outcomes.

Background: This study aimed to explore the process, clinical, and patient-reported outcomes of older adults who received an interdisciplinary Comprehensive Geriatric Assessment (CGA) in the emergency department (ED) over a six-month period after their initial ED attendance. Patients and Methods: A prospective cohort study recruited older adults aged ≥65 years who presented to the ED of a university teaching hospital in Ireland. Baseline assessment data comprising a battery of demographic variables and validated indices were obtained at the index ED attendance. Telephone interviews were completed with participants at 30- and 180-day follow-up. The primary outcome was incidence of hospital admission following the index ED attendance. Secondary outcomes included participant satisfaction, incidence of functional decline, health-related quality of life, incidence of unscheduled ED re-attendance(s), hospital (re)admission(s), nursing home admission, and death. Results: A total of 133 participants (mean age 82.43 years, standard deviation = 6.89 years; 71.4% female) were recruited; 21.8% of the cohort were admitted to hospital following the index ED attendance with a significant decline in function reported at hospital discharge (Z = 2.97, p = 0.003). Incidence of 30- and 180-day unscheduled ED re-attendance was 10.5% and 24.8%, respectively. The outcome at the index ED attendance was a significant predictor of adverse outcomes whereby those who were discharged home had significantly lower odds of multiple adverse process outcomes at 30- and 180-day follow-up, and significantly higher function and health-related quality of life at 30-day follow-up. Conclusion: While this study was observational in nature, findings suggest CGA in the ED may improve outcomes by mitigating against the adverse effects of potentially avoidable hospital admissions and focusing on a longitudinal approach to healthcare delivery at the primary-secondary care interface. Future research should be underpinned by an experimental study design to address key limitations in this study.

A Physiotherapy-Led Transition to Home Intervention for Older Adults Following Emergency Department Discharge: A Pilot Feasibility Randomised Controlled Trial (ED PLUS).

Background: Older adults frequently attend the emergency department (ED) and experience high rates of subsequent adverse outcomes including functional decline, ED re-presentation and unplanned hospital admission. The development of effective interventions to prevent such outcomes is a key priority for research and service provision. Our aim was to evaluate the feasibility of a physiotherapy-led integrated care intervention for older adults discharged from the ED (ED PLUS). Patients and Methods: Older adults presenting to the ED of a university teaching hospital with undifferentiated medical complaints and discharged within 72 hours were computer randomised in a ratio of 1:1:1 to deliver usual care, Comprehensive Geriatric Assessment (CGA) in the ED, or ED PLUS. ED PLUS is an evidence-based and stakeholder-informed intervention to bridge the care transition between the ED and community by initiating a CGA in the ED and implementing a six-week, multi-component, self-management programme in the patient's home. Feasibility and acceptability were assessed quantitatively and qualitatively. All clinical and process outcomes were assessed by a research nurse blinded to group allocation. Data analyses were primarily descriptive. Results: Twenty-nine participants were recruited indicating a 67% recruitment rate. At 6 months, there was 100% retention in the usual care group, 88% in the CGA group and 90% in the ED PLUS group. ED PLUS participants expressed positive feedback, and there was a trend towards improved function and quality of life and less ED revisits and unscheduled hospitalisations in the ED PLUS group. Conclusion: ED PLUS bridges the transition of care between the index visit to the ED and the community and is feasible using systematic recruitment strategies. Despite recruitment challenges in the context of COVID-19, the intervention was successfully delivered and well received by participants. There was a lower incidence of functional decline and improved quality of life in the ED PLUS group. Trial Registration: The trial was registered in Clinical Trials Protocols and Results System as of 21st July 2021, with registration number NCT04983602.

Antipsychotic drug prescribing and mortality in people with dementia before and during the COVID-19 pandemic: a retrospective cohort study in Wales, UK.

BACKGROUND: Concerns have been raised that antipsychotic drug prescribing, which has been associated with increased mortality in people with dementia, might have increased during the COVID-19 pandemic due to social restrictions imposed to limit the spread of SARS-CoV-2. We used multisource, routinely collected health-care data from Wales, UK to investigate prescribing and mortality variations in people with dementia before and during the COVID-19 pandemic. METHODS: In this retrospective cohort study, we used individual-level, anonymised, population-scale linked health data to identify adults aged 60 years and older with a diagnosis of dementia in Wales, UK. We used the CVD-COVID-UK initiative to access Welsh routinely collected electronic health record data from the Secure Anonymised Information Linkage (SAIL) Databank. Patients who were alive and registered with a SAIL general practice on Jan 1, 2016, and who received a dementia diagnosis before the age of 60 years and before or during the study period were included. We explored antipsychotic drug prescribing rate changes over 67 months, between Jan 1, 2016, and Aug 1, 2021, overall and stratified by age and dementia subtype. We used time-series analyses to examine all-cause and myocardial infarction and stroke mortality over the study period and identified the leading causes of death in people with dementia between Jan 1, 2020, and Aug 1, 2021. FINDINGS: Of 3 106 690 participants in SAIL between Jan 1, 2016 and Aug 1, 2021, 57 396 people (35 148 [61·2%] women and 22 248 [38·8%] men) met inclusion criteria for this study and contributed 101 428 person-years of follow-up. Of the 57 396 people with dementia, 11 929 (20·8%) were prescribed an antipsychotic drug at any point during follow-up. Accounting for seasonality, antipsychotic drug prescribing increased during the second half of 2019 and throughout 2020. However, the absolute difference in prescribing rates was small, ranging from 1253 prescriptions per 10 000 person-months in March, 2019, to 1305 per 10 000 person-months in September, 2020. All-cause mortality and stroke mortality increased throughout 2020, while myocardial infarction mortality declined. From Jan 1, 2020, to Aug 1, 2021, 1286 (17·1%) of 7508 participants who died had COVID-19 recorded as the underlying cause of death. INTERPRETATION: During the COVID-19 pandemic, antipsychotic drug prescribing in people with dementia in the UK increased slightly; however, it is unlikely that this was solely related to the pandemic and this increase was unlikely to be a major factor in the substantial increase in mortality during 2020. The long-term increase in antipsychotic drug prescribing in younger people and in those with Alzheimer's disease warrants further investigation using resources with access to more granular clinical data. Although deprescribing antipsychotic medications remains an essential aspect of dementia care, the results of this study suggest that changes in prescribing and deprescribing practices as a result of the COVID-19 pandemic are not required. FUNDING: British Heart Foundation (via the British Heart Foundation Data Science Centre led by Health Data Research UK), and the Scottish Neurological Research Fund.

Multidisciplinary inpatient rehabilitation for older adults with COVID-19: a systematic review and meta-analysis of clinical and process outcomes.

BACKGROUND: Older adults are at increased risk for disease severity and poorer prognosis following COVID-19 infection. The aim of this systematic review and meta-analysis is to explore the impact of multidisciplinary rehabilitation in the acute or post-acute hospital setting for older adults with COVID-19. METHODS: The Cochrane library, EMBASE, Cinahl and Medline (via EBSCO), PubMed, and Web of Science were systematically searched in June 2022 and a repeat search was completed in March 2023. Screening, data extraction and quality appraisal were conducted independently by two reviewers. Studies reporting outcomes for older adults following multidisciplinary rehabilitation (provided by two or more Health and Social Care Professionals) were included. Both observational and experimental study designs were included. The primary outcome was functional ability. Secondary outcomes included discharge disposition, acute hospital and rehabilitation unit length of stay, mortality, primary and secondary healthcare utilisation, and long-term effects of COVID-19. RESULTS: Twelve studies met the inclusion criteria, comprising a total of 570 older adults. Where reported, older adults stayed in the acute hospital for a mean of 18 days (95%CI, 13.35- 23.13 days) and in rehabilitation units for 19 days (95%CI, 15.88-21.79 days). There was a significant improvement in functional ability among older adults with COVID-19 who received multidisciplinary rehabilitation (REM, SMD = 1.46, 95% CI 0.94 to 1.98). The proportion of older adults who were discharged directly home following rehabilitation ranged from 62 to 97%. Two studies reported a 2% inpatient mortality rate of older persons during rehabilitative care. No study followed up patients after the point of discharge and no study reported on long term effects of COVID-19. CONCLUSIONS: Multidisciplinary rehabilitation may result in improved functional outcomes on discharge from rehabilitation units/centres for older adults with COVID-19. Findings also highlight the need for further research into the long-term effect of rehabilitation for older adults following COVID-19. Future research should comprehensively describe multidisciplinary rehabilitation in terms of disciplines involved and the intervention provided.

The Gender-Specific Relationship between Nutritional Status, Physical Activity and Functional Mobility in Irish Community-Dwelling Older Adults.

Research suggests that both nutrition and physical activity can protect mobility in older adults, but it is yet to be determined whether these relationships are affected by gender. Thus, we investigated the gender-specific relationship between nutritional status, physical activity level and functional mobility in Irish older adults. A cross-sectional study was undertaken in 176 community-dwelling older adults (73.6 ± 6.61 years) living in Cork, Ireland. Nutritional status was measured using the Mini Nutritional Assessment-Short Form (MNA-SF) and physical activity was assessed via the Physical Activity Scale for the Elderly (PASE). Functional mobility was measured using the Timed Up and Go (TUG) test. The gender-stratified relationship between variables was assessed using Pearson's correlations and multiple linear regression. Partial correlations (p < 0.05) were observed for TUG with PASE score in both genders, and with MNA-SF score in females, only. Multiple regression showed that physical activity was a predictor of TUG in both genders (ß = 0.257 for males, ß = 0.209 for females, p < 0.05), while nutritional status was a predictor of TUG in females, only (ß = -0.168, p = 0.030). Our results suggest that physical activity is associated with functional mobility in both genders, while the relationship between nutritional status and mobility may be specific to older females. These findings may be of interest for the design of functional preservation strategies.

The nutritional status and dietary intake of free-living seniors: A cross-sectional study.

BACKGROUND AND AIMS: Older adults are a population group at risk of inadequate nutrition due to reduced appetite, malabsorption, taste alterations and social factors. Yet, dietary investigations in Irish older adults are scarce. The aim of this study was to analyse the nutritional status and dietary intake of a sample of community-dwelling Irish elderly, in addition to the effect of age and gender on dietary intake in this age group. METHODS: A cross-sectional study was performed in 162 (n = 91 female, n = 71 male, age 73.8 ± 6.8 years) adults aged 65 years and over in a region of Southern Ireland. Nutritional status was measured using the Mini Nutritional Assessment - Short Form (MNA-SF). Dietary intake was assessed using a semi-quantitative food frequency questionnaire (FFQ). RESULTS: 21.0% and 1.2% of the study population were at risk of malnutrition and malnourished, respectively. A high prevalence of dietary insufficiencies was observed. The most common insufficiencies reported were energy (54.9%), fibre (82.7%), calcium (58.6%), magnesium (62.3%), iron (54.9%), folate (66.0%), vitamin D (93.2%) and vitamin E (61.1%). Increasing age did not significantly influence nutrient intakes in males, while vitamin C and vitamin D intakes decreased with age in females, and the incidence of dietary folate insufficiency was higher in the oldest females. Gender differences in dietary intake were evident, with a higher prevalence of dietary inadequacy in male subjects. Excessive intake of sugars, snacks and fats was observed, particularly in males, while dairy recommendations were not being met. Dietary supplement use was rare (27.2%). CONCLUSIONS: The poor dietary quality of this cohort may have significant health implications. Public health strategies to improve the diets of older adults are warranted, with a particular focus on increasing micronutrient intakes.

Applications of Circulating Tumor DNA in a Cohort of Phase I Solid Tumor Patients Treated With Immunotherapy.

Background: The correlation between blood-based tumor mutation burden (bTMB) and tissue-based tumor mutation burden(tTMB) has not been broadly tested in a multicancer cohort. Here, we assess the correlation between bTMB with tTMB in phase I trial patients treated with immunotherapy. As an exploratory analysis, we evaluated circulating tumor DNA (ctDNA) dynamics in responders. Methods: Patients treated with immunotherapy at the Princess Margaret phase I trials unit were enrolled. Pretreatment plasma ctDNA and matched normal blood controls were collected. Available archival tissue formalin-fixed paraffin-embedded (FFPE) samples were analyzed. A 425-gene panel was used to sequence both ctDNA and FFPE samples. Samples with TMB within the highest tertile were considered as high TMB. Results: Thirty-eight patients were accrued from 25 different trials, 86.8% of which involved an anti-PD-1/PD-L1 agent. Thirty patients (78.9%) had detectable mutations in ctDNA, of which the median (range) bTMB was 5 (1-53) mutations per megabase (mut/Mb). Of the 22 patients with available FFPE samples, mutations were detected in 21 (95.4%); the median (range) tTMB was 6 (2-124) mut/Mb. Among the 16 patients with detectable mutations in both FFPE and ctDNA, a statistically significant correlation between bTMB and tTMB was observed (ρ = 0.71; P = .002). High TMB was not associated with better survival. All 3 responders had a decrease in the variant allele frequency of mutations detected in ctDNA at a second timepoint relative to baseline, indicating a potential early marker of response. Conclusions: In this small series, bTMB correlated with tTMB. An on-treatment decrease in VAF of mutations detected in ctDNA at baseline was observed in responders. Larger studies to verify our findings are warranted.

Associations between Food Group Intake and Physical Frailty in Irish Community-Dwelling Older Adults.

BACKGROUND: Certain nutrients have shown protective effects against frailty, but less is known about the influence of individual food groups. Thus, this study aimed to investigate the relationship between the intake of different food groups and physical frailty in a cohort of community-dwelling older adults in Cork, Ireland. METHODS: One hundred and forty-two (n = 81 females, n = 61 males, age 74.1 ± 6.80 years) Irish community-dwelling volunteers aged ⩾65 years participated in this cross-sectional study. Dietary intake was assessed using a validated food frequency questionnaire (FFQ). Frailty was identified as having 3 or more of the following criteria: weight loss, exhaustion, weakness, slow walking speed and low physical activity. Relationships between intakes of food groups and frailty score were determined using Spearman's rank (and partial rank) correlations and ordinal logistic regression analysis. RESULTS: Negative Spearman's rank correlations were observed between frailty score and fish and fish products, fruit and vegetables and nuts and seeds, while positive correlations were found between frailty score and potatoes, fats and oils and sugars, preserves and snacks (P < .05). After adjustment for confounders, partial rank correlations remained statistically significant (P < .05) for all of the above dietary variables, with the exception of nuts and seeds (P > .05). Following ordinal logistic regression, the odds ratios (ORs) (95%CI) for frailty incidence for those in the lowest tertile of food group intake compared to the highest were; 3.04 (1.09-8.85) for fish and fish products, 4.34 (1.54-13.13) for fruit and vegetables, 1.52 (0.58-4.15) for nuts and seeds, 0.54 (0.19-1.51) for potatoes, 0.58 (0.17-1.95) for fats and oils and 0.49 (0.16-1.47) for sugars, preserves and snacks. CONCLUSION: This study suggests that intakes of selected food groups are independently associated with frailty. These findings may hold significant relevance for the development of future frailty prevention strategies.

Identifying dietary patterns in Irish schoolchildren and their association with nutritional knowledge and markers of health before and after intervention.

The aim of the study was to identify dietary patterns (DP) and examine differences in anthropometric measures, blood pressure (BP), cardiorespiratory fitness and nutritional knowledge of 6- and 10-year-old children at baseline and following a nutrition and physical activity intervention, with respect to DP and treatment group. This is a longitudinal study. Food diary, nutritional knowledge questionnaire and 550-m walk/run test measured dietary intake, nutritional knowledge and cardiorespiratory fitness, respectively. BP, weight, height and waist circumference were also measured and BMI and waist-to-height ratio (WHtR) were derived. All measurements were performed at baseline and following intervention. Two primary schools (one intervention, one control) in Cork, Ireland, were selected. Participants were 6- (n 39, age 5·9 (sd 0·6) years) and 10- (n 49, age 9·8 (sd 0·5) years)-year-olds. Two DP were identified, using k-means cluster analysis, for both 6- (unhealthy and nutrient-dense) and 10-year-olds (processed and Western diet) at baseline. DP derived post-intervention were (1) plant-based and (2) processed foods for 6-year-olds and (1) nutrient-dense and (2) unhealthy for 10-year-olds. There was no statistically significant difference in DP for 6- and 10-year-olds at baseline and post-intervention (P > 0·05). Following the intervention, a multivariate ANOVA showed there were no statistically significant differences in nutritional knowledge, BMI, WHtR, cardiorespiratory fitness and BP based on DP and intervention/control group for both age groups (P > 0·05). Three out of four dietary patterns identified for 6- and 10-year-olds were unfavourable. While no statistically significant evidence of intervention impact was found on DP, a positive trend was emerging among 10-year-olds.

Dietary protein considerations for muscle protein synthesis and muscle mass preservation in older adults.

Amino acid bioavailability is critical for muscle protein synthesis (MPS) and preservation of skeletal muscle mass (SMM). Ageing is associated with reduced responsiveness of MPS to essential amino acids (EAA). Further, the older adult population experiences anabolic resistance, leading to increased frailty, functional decline and depleted muscle mass preservation, which facilitates the need for increased protein intake to increase their SMM. This review focuses on the role of proteins in muscle mass preservation and examines the contribution of EAA and protein intake patterns to MPS. Leucine is the most widely studied amino acid for its role as a potent stimulator of MPS, though due to inadequate data little is yet known about the role of other EAA. Reaching a conclusion on the best pattern of protein intake has proven difficult due to conflicting studies. A mixture of animal and plant proteins can contribute to increased MPS and potentially attenuate muscle wasting conditions; however, there is limited research on the biological impact of protein blends in older adults. While there is some evidence to suggest that liquid protein foods with higher than the RDA of protein may be the best strategy for achieving high MPS rates in older adults, clinical trials are warranted to confirm an association between food form and SMM preservation. Further research is warranted before adequate recommendations and strategies for optimising SMM in the elderly population can be proposed.

Cheese as a functional food for older adults: comparing the bioactive properties of different cheese matrices following simulated gastrointestinal in vitro digestion.

Age-related changes to the gastrointestinal tract (GIT) can impact how food is digested. Studying the effects of these changes can help identify functional foods for older adults. Cheese was digested using two simulated gastrointestinal in vitro digestion (SGID) models representing adult and elderly gastro-intestinal conditions. Antioxidant capacity was measured using DPPH, FRAP and TPC assays. The ability of cheese to inhibit digestive enzymes was determined by the α-glucosidase and lipase inhibition assays. Digestive aging influenced the bioactivity of cheese, as elderly digestates had significantly lower (p < 0.05) antioxidant, α-glucosidase and lipase inhibitory properties compared to adult digestates. However, soft cheese (feta, goats', brie) demonstrated greatest potential with comparable radical scavenging properties and lipase inhibition, greatest FRAP and α-glucosidase inhibitory potential. Despite age-related changes, the bioactive properties of cheese were evident following digestion with an older adult SGID model, suggesting cheese has potential as a functional food for older adults.

A 34-Year-Old Man With a Chylothorax and Bony Pain.

CASE PRESENTATION: A 34-year-old man presented to a community hospital with sudden-onset pleuritic chest pain on a background of a 12-month indolent history of progressive exertional dyspnea. He denied cough, fevers, night sweats, or weight loss. He reported some low back pain and ache. He had a history of gastroesophageal reflux and was a current smoker with a 20-pack year history. There were no known occupational or environmental exposures and there was no family history of any lung disease.

The role of nutrition and physical activity in frailty: A review.

Frailty is a clinical syndrome with a worldwide prevalence of 5-27% among those aged over 65 years. Frailty is characterised by loss of muscle strength and impaired physical function, and is associated with increased falls, hospitalisation and death. Nutritional deficiencies and low physical activity are common in this age group due to ill health, disability and reductions in enthusiasm, food intake and therefore, energy availability. Both low physical activity and inadequate dietary intake have a significant role to play in the onset and progression of frailty, primarily through bone and muscle health implications. Frailty is, however, preventable and reversible, and several interventions have been carried out to offset and reverse the condition. This article reports the recent evidence on the role of nutrition and physical activity in the pathogenesis of frailty and provides a critical review of previously implemented interventions focussed on physical activity and nutrition to prevent and reduce frailty among older adults.

Unique MLH1 mutations in colonic adenomas in an obligate germline Lynch syndrome carrier.

BACKGROUND: An obligate germline Lynch syndrome carrier had four colonic adenomas removed. MATERIALS AND METHODS: The adenomas were evaluated for grade of dysplasia, MLH1, PMS2, MSH2 and MSH6 protein expression, microsatellite instability (MSI), BRAF, methylation status and a next-generation sequencing (NGS) panel of 52 cancer genes. RESULTS: There were four tubular or tubulovillous adenomas from the hepatic flexure, rectosigmoid and rectum; one with low-grade and high-grade dysplasia, one with high-grade dysplasia only and two with low-grade dysplasia. All four adenomas showed retention of MLH1, MHS2 and MSH6 but complete loss of PMS2 in both low-grade and high-grade dysplasia areas.Two of the four adenomas were MSI-high, BRAF V600E wild type and were not MLH1 methylated. NGS identified an MLH1 germline variant: NM_000249.3: c.1558+1 G>A, p.(?) in all tissue (adenomas and normal), which likely explains the pathophysiology of Lynch syndrome in this patient. Other variants were also detected in MLH1 and MSH6 in all four adenomas tested; these being reported previously in somatic colorectal cancers. CONCLUSION: We highlight an MLH1 variant in the colonic adenomas in an obligate Lynch syndrome carrier that resulted in PMS2 protein loss in the absence of mutations of the PMS2 gene.

Traditional serrated adenoma: an overview of pathology and emphasis on molecular pathogenesis.

OBJECTIVE: To provide an overview of the pathology and molecular pathogenesis of traditional serrated adenomas (TSA). DESIGN: Describe the morphology and molecules that play a role in their pathogenesis. RESULTS: These exuberant polypoid lesions are typified by tall cells with deeply eosinophilic cytoplasm, elongated nuclei bearing delicate chromatin, ectopic crypt foci, deep clefting of the lining mucosa and an overall resemblance to small bowel mucosa.Broadly, TSAs arise via three mechanisms. They may be BRAF mutated and CpG island methylator phenotype (CIMP)-high: right sided, mediated through a microvesicular hyperplastic polyp or a sessile serrated adenoma, may also have RNF43 mutations and result in microsatellite stable (MSS) colorectal cancers (CRC). The second pathway that is mutually exclusive of the first is mediated through KRAS mutation with CIMP-low TSAs. These are left-sided TSAs, are not associated with another serrated polyp and result in MSS CRC. These TSAs also have RSPO3, RNF43 and p53 mutations together with aberrant nuclear localisation of ß-catenin. Third, there is a smaller group of TSAs that are BRAF and KRAS wild type and arise by as yet unknown molecular events. All TSAs show retention of mismatch repair proteins. CONCLUSION: These are characteristic unusual polyps with a complex molecular landscape.

Project Spraoi: a two-year longitudinal study on the effectiveness of a school-based nutrition and physical activity intervention on dietary intake, nutritional knowledge and markers of health of Irish schoolchildren.

OBJECTIVE: To assess the effectiveness of a nutrition and physical activity (PA) intervention on dietary intake (DI), nutritional knowledge (NK), blood pressure (BP), anthropometric measures and cardiorespiratory fitness (CRF) of schoolchildren. DESIGN: Longitudinal study. DI, NK, BMI, waist-to-height ratio (WHtR), BP and CRF were all measured/calculated prior to (October 2014) and at the end of (June 2016) intervention delivery. SETTING: Two primary schools (one intervention and one control), Cork, Ireland. PARTICIPANTS: Six-year-olds (n 49; mean age = 6·09 (sd 0·33) years) and 10-year-olds (n 52; mean age = 9·90 (sd 0·37) years). RESULTS: There was a large and a moderate statistically significant difference between the change in systolic (P = 0·005, effect size (ES) = 0·165) and diastolic BP (P = 0·023, ES = 0·116), respectively, for 10-year-olds in the intervention and control groups. There was also a large statistically significant difference between the change in WHtR (P = 0·0005, ES = 0·386) and a moderate statistically significant difference between the change in NK (P = 0·027, ES = 0·107) for 10-year-olds in the intervention and control groups. There was a large statistically significant difference between the change in percentage of energy from protein in 10-year-old females (P = 0·021, ES = 0·276) in the intervention and control groups. CONCLUSIONS: Project Spraoi is Ireland's first ever school-based intervention that has been evaluated and proven effective in improving DI, NK, WHtR and BP in older primary-school children in one intervention school.

Metastatic low-grade endometrial stromal sarcoma of uterus presenting as a primary pancreatic tumor: case presentation and literature review.

BACKGROUND: Metastatic tumors to the pancreas are uncommon, accounting for approximately 2% of pancreatic malignancies. The most common primary tumors to give rise to pancreatic metastases are carcinomas. CASE PRESENTATION: A 50-year old female patient was investigated for a cause of abdominal discomfort. She had a 2-year history of menorrhagia and dysmenorrhea which was ascribed to a fibroid uterus. On imaging, she was found to have a large solid and cystic mass in the tail of the pancreas. Imaging also confirmed a fibroid uterus. A distal pancreatectomy and splenectomy showed a 9 cm circumscribed mass within, and grossly confined to, the parenchyma of the pancreatic tail. Microscopically, the pancreatic lesion was lobulated, and well-circumscribed, but focally infiltrative. It comprised sheets of uniform spindled to epithelioid cells with round to oval nuclei, coarse to vesicular chromatin, visible nucleoli, nuclear grooves and clear to eosinophilic cytoplasm. Prominent arterioles were identified. The stroma was collagenized in areas. Occasional hemosiderin-laden macrophages were seen, and focal cystic change was present. There was no evidence of nuclear pleomorphism, mitotic activity or necrosis, and there was no evidence of endometriosis despite multiple sections being taken. Immunohistochemistry showed that the tumor cells were positive for CD10, estrogen receptor (ER), progesterone receptor (PR), Wilms tumor-1 (WT-1) and smooth muscle actin (SMA). RNA sequencing detected a PHF1 rearrangement. The morphological, immunohistochemical and molecular features were of a low-grade endometrial stromal sarcoma (LG-ESS). Subsequent total hysterectomy and bilateral salpingo-oophorectomy 3 months later, showed uterine fibroids and a 5 cm low-grade endometrial stromal sarcoma confined to the uterus, with lymphatic invasion. CONCLUSIONS: To the best of our knowledge, this is the first documented case of metastatic endometrial stromal sarcoma of uterus presenting as a primary pancreatic neoplasm. An unexpected extra-uterine location and unusual presentation of ESS may make the diagnosis challenging, despite classic histological features. Morphological, immunohistochemical and molecular findings must be combined to render the correct diagnosis.

Gut-associated lymphoid tissue or so-called "dome" carcinoma of the colon: Review.

AIM: To present a comprehensive review of the etiology, clinical features, macroscopic and pathological findings, and clinical significance of Gut-associated lymphoid tissue or "dome" carcinoma of the colon. METHODS: The English language medical literature on gut- or gastrointestinal-associated lymphoid tissue (GALT) or "dome" carcinoma of the colon was searched and appraised. RESULTS: GALT/dome-type carcinomas of the colon are thought to arise from the M-cells of the lymphoglandular complex of the intestine. They are typically asymptomatic and have a characteristic endoscopic plaque- or "dome"-like appearance. Although the histology of GALT/dome-type carcinomas displays some variability, they are characterized by submucosal localization, a prominent lymphoid infiltrate with germinal center formation, tumor-infiltrating lymphocytes, absence of desmoplasia, and dilated glands lined by columnar epithelial cells with bland nuclear features and cytoplasmic eosinophilia. None of the patients reported in the literature with follow-up have developed metastatic disease or local recurrence. CONCLUSION: Increased awareness amongst histopathologists of this variant of colorectal adenocarcinoma is likely to lead to the recognition of more cases.

Neoadjuvant therapy in gynaecological malignancies: What pathologists need to know.

In recent times, there has been a growing tendency to treat advanced gynaecological malignancies with neoadjuvant chemotherapy (NACT), with the goal of reducing tumour volume and enhancing operability resulting in optimal cytoreduction. This approach is used in particular for patients with advanced high-grade serous carcinoma of the ovary, fallopian tube or peritoneum. Pathology plays a crucial role in the management of these patients, both before and after NACT. Prior to initiation of NACT, a biopsy should be performed, usually of the omental cake, to confirm that a malignancy is present, to identify the site of origin of the tumour and to type and grade the tumour. Histopathologists must be aware of the resultant morphological effects of NACT when examining specimens following interval cytoreduction surgery. Tumour typing and grading, and even the identification of residual neoplasia, are particular challenges. Immunohistochemistry, when used judiciously, can be a useful adjunct in certain scenarios. A pathological assessment of the response to chemotherapy, and the pathological stage should be provided in the pathology report, as these may inform prognosis and subsequent management. We present a comprehensive overview of the relevant clinical and pathological aspects pertaining to NACT for gynaecological malignancies for the practicing surgical pathologist.