The appendix "mucocoele" misnomer: radiological terminology of "likely appendix mucinous neoplasm" better reflects pathology findings.

AIM: To review the radiological terminology used to describe dilated mucin-containing appendiceal lesions with correlation to the histopathological diagnosis. MATERIALS AND METHODS: Radiology and histopathology reports for all patients with an abnormally dilated appendix referred to a tertiary peritoneal malignancy centre, between January 2021 and December 2021, were reviewed. RESULTS: Overall, 213 patients were included with a median appendiceal diameter of 25.5 mm (range 10-125 mm). Peritoneal disease was present in 109 patients, with the remaining 104 cases demonstrating a dilated appendix only. Local radiology reports were available for 201 cases with the appendix described in 168 cases as appendiceal mucocoele (n=104), appendiceal neoplasm (n=40), appendicitis (n=18), and dilated appendix (n=6). The appendix was not mentioned in 33/201 (15%), either misinterpreted as other pathology (n=15) or not reported (n=18). Peritoneal malignancy histopathology reports were available in 188 cases and reported as low-grade appendix mucinous neoplasm (LAMN, n=144), high-grade appendix mucinous neoplasm (HAMN, n=13), LAMN with foci of HAMN (n=2), LAMN with neuroendocrine tumour (n=2), LAMN with goblet cell adenocarcinoma (n=1), goblet cell adenocarcinoma (n=8), mucinous adenocarcinoma (n=14), non-mucinous adenocarcinoma (n=1), and benign histology (n=3). Only one case of a true inflammatory "mucocoele"/retention cyst was reported. CONCLUSION: In this cohort of patients, the overwhelming majority of dilated, mucin-filled appendices contained malignant cells and benign mucin-filled appendices were rare. The present authors advocate that the term "likely appendix mucinous neoplasm" should replace "appendix mucocoele" to represent the most likely pathology and facilitate less ambiguous interpretation in management decisions.

Evaluating the effects of grass management technologies on the physical, environmental, and financial performance of Irish pasture-based dairy farms.

Grass management technologies (grass measuring devices and grassland management decision support tools) have been identified as important tools to improve the performance of pasture-based dairy farms. They have the potential to significantly improve the efficiency and sustainability of dairy systems by increasing milk production through enhanced pasture growth and utilization, which would reduce the need for supplementary feeds, along with increased output, therefore increasing farm profitability and environmental sustainability. Despite the several potential benefits of grass management technologies, there is a lack of empirical research around the effects of these technologies on the performance of pasture-based dairy systems. The current study aimed to fill this knowledge gap by using a 2018 nationally representative survey of Irish dairy farms and a propensity score matching approach to determine the effects of adopting grass management technologies on the physical, environmental, and financial performance of Irish pasture-based dairy farms. The findings showed that dairy farms utilizing grass management technologies had, on average, higher farm physical, environmental, and financial performance (in terms of grazed pasture use, total pasture use, length of the grazing season, milk yield, milk solids, greenhouse gas emissions per kilogram of fat- and protein-corrected milk, gross output, and gross margin) compared with dairy farms not utilizing these technologies. However, when controlling for selection bias, we can only attribute a positive causal effect of grass management technology adoption on the use of grazed pasture per cow, grazing season length, milk yield per cow, and milk solids per cow. This might be due to dairy farmers not yet using the technologies to their full potential, 2018 being an unusual year in terms of weather (and therefore not being able to capture the full range of farm performance benefits), or because grass management technologies need to be adopted in association with other technologies and practices to achieve their expected performance outcomes. Future research should include updated farm-level data to capture the weather and learning effects and so be able to determine the impact of grass management technologies on a wider range of performance indicators.

Factors associated with intensity of technology adoption and with the adoption of 4 clusters of precision livestock farming technologies in Irish pasture-based dairy systems.

Precision livestock farming (PLF) technologies have been widely promoted as important tools to improve the sustainability of dairy systems due to perceived economic, social, and environmental benefits. However, there is still limited information about the level of adoption of PLF technologies (percentage of farms with a PLF technology) and the factors (farm and farmer characteristics) associated with PLF technology adoption in pasture-based dairy systems. The current research aimed to address this knowledge gap by using a representative survey of Irish pasture-based dairy farms from 2018. First, we established the levels of adoption of 9 PLF technologies (individual cow activity sensors, rising plate meters, automatic washers, automatic cluster removers, automatic calf feeders, automatic parlor feeders, automatic drafting gates, milk meters, and a grassland management decision-support tool) and grouped them into 4 PLF technology clusters according to the level of association with each other and the area of dairy farm management in which they are used. The PLF technology clusters were reproductive management technologies, grass management technologies, milking management technologies, and calf management technologies. Additionally, we classified farms into 3 categories of intensity of technology adoption based on the number of PLF technologies they have adopted (nonadoption, low intensity of adoption, and high intensity of adoption). Second, we determined the factors associated with the intensity of technology adoption and with the adoption of the PLF technology clusters. A multinomial logistic regression model and 4 logistic regressions were used to determine the factors associated with intensity of adoption (low and high intensity of adoption compared with nonadoption) and with the adoption of the 4 PLF technology clusters, respectively. Adoption levels varied depending on PLF technology, with the most adopted PLF technologies being those related to the milking process (e.g., automatic parlor feeders and milk meters). The results of the multinomial logistic regression suggest that herd size, proportion of hired labor, agricultural education, and discussion group membership were positively associated with a high intensity of adoption, whereas age of farmer and number of household members were negatively associated with high intensity of adoption. However, when analyzing PLF technology clusters, the magnitude and direction of the influence of the factors in technology adoption varied depending on the PLF technology cluster being investigated. By identifying the PLF technologies in which pasture-based dairy farmers are investing more and by detecting potential drivers and barriers for the adoption of PLF technologies, the current study could allow PLF technology companies, practitioners, and researchers to develop and target strategies that improve future adoption of PLF technologies in pasture-based dairy settings.

Colorectal cancer outcomes determined by mode of presentation: analysis of population data in England between 2010 and 2014.

BACKGROUND: The purpose of this study was to investigate associations between mode of presentation; categorized as emergency, suspected cancer outpatient referral pathway (2-week wait or 2WW pathway), non-cancer suspected outpatient referral (non-2-week wait pathway) or following screening, and stage of diagnosis and survival in patients with colorectal cancer in England. METHODS: This was a retrospective cohort observational study of patients diagnosed with colorectal cancer between January 2010 and December 2014 in England using data from Public Health England collated from regional cancer registries. RESULTS: The most common route to diagnosis among 167,501 patients diagnosed with colorectal cancer was via the non-cancer suspect (non-2WW) outpatient referral pathway (35.1%) followed by the suspected cancer (2WW) referral pathway (31.6%), emergency presentation (22.8%) and most infrequently following screening (10.6%) (p < 0.01). Screening confers the greatest likelihood of early-stage diagnosis (61.6%) compared to other modes of presentation. The 5-year overall survival was 81.8%, 53.3%, 53.0% and 27.6% in those diagnosed via screening, 2WW, non-2WW pathway and emergency presentation, respectively. Patients from most deprived regions were more likely to be diagnosed following emergency presentation (27.7 vs 19.7%, p < 0.01) and less likely via screening (8.1 vs 12%, p < 0.01). CONCLUSIONS: Asymptomatic individuals diagnosed following screening have earlier stage cancers and better survival, the opposite was observed in those diagnosed following emergency presentation. Patients referred via the 2WW pathway do not have better survival outcomes when compared to those referred via the non-2WW pathway. In addition, this study has identified socio-economic groups that need to be targeted with public health campaigns to improve screening uptake.

The role of infiltrating lymphocytes in the neo-adjuvant treatment of women with HER2-positive breast cancer.

BACKGROUND: Pre-treatment tumour-associated lymphocytes (TILs) and stromal lymphocytes (SLs) are independent predictive markers of future pathological complete response (pCR) in HER2-positive breast cancer. Whilst studies have correlated baseline lymphocyte levels with subsequent pCR, few have studied the impact of neoadjuvant therapy on the immune environment. METHODS: We performed TIL analysis and T-cell analysis by IHC on the pretreatment and 'On-treatment' samples from patients recruited on the Phase-II TCHL (NCT01485926) clinical trial. Data were analysed using the Wilcoxon signed-rank test and the Spearman rank correlation. RESULTS: In our sample cohort (n = 66), patients who achieved a pCR at surgery, post-chemotherapy, had significantly higher counts of TILs (p = 0.05) but not SLs (p = 0.08) in their pre-treatment tumour samples. Patients who achieved a subsequent pCR after completing neo-adjuvant chemotherapy had significantly higher SLs (p = 9.09 × 10-3) but not TILs (p = 0.1) in their 'On-treatment' tumour biopsies. In a small cohort of samples (n = 16), infiltrating lymphocyte counts increased after 1 cycle of neo-adjuvant chemotherapy only in those tumours of patients who did not achieve a subsequent pCR. Finally, reduced CD3 + (p = 0.04, rho = 0.60) and CD4 + (p = 0.01, rho = 0.72) T-cell counts in 'On-treatment' biopsies were associated with decreased residual tumour content post-1 cycle of treatment; the latter being significantly associated with increased likelihood of subsequent pCR (p < 0.01). CONCLUSIONS: The immune system may be 'primed' prior to neoadjuvant treatment in those patients who subsequently achieve a pCR. In those patients who achieve a pCR, their immune response may return to baseline after only 1 cycle of treatment. However, in those who did not achieve a pCR, neo-adjuvant treatment may stimulate lymphocyte influx into the tumour.

Dimethyl fumarate modulates the Treg-Th17 cell axis in patients with psoriasis.

BACKGROUND: Dimethyl fumarate (DMF) is the active ingredient of Skilarence™ and Tecfidera™, which are used for the treatment of psoriasis and multiple sclerosis, respectively. Various immunomodulatory mechanisms of action have been identified for DMF; however, it is still unclear what effects DMF exerts in vivo in patients with psoriasis. OBJECTIVES: In this study we examined the effects of DMF, both in vivo and in vitro, on T cells, which play a key role in the pathogenesis of psoriasis. METHODS: The frequency of T-cell subsets was examined by flow cytometry in untreated patients with psoriasis or those treated with DMF. The effects of DMF in vitro on T-cell survival, activation and proliferation, and cell-surface thiols were assessed by flow cytometry. RESULTS: In patients with psoriasis treated with DMF we observed an increase in the frequency of T regulatory (Treg) cells and a decrease in T helper (Th)17 lineage cells and the associated cytokines interleukin-17, interleukin-22 and granulocyte-macrophage colony-stimulating factor. T cells cultured in vitro with DMF exhibited reduced viability, and inhibition of activation and proliferation in response to stimulation due to the oxidative effects of DMF. However, the frequency of Treg cells increased in the presence of DMF due to their heightened ability to resist DMF-induced oxidative stress. CONCLUSIONS: DMF enhanced the ratio of Treg cells to Th17 cells in patients with psoriasis, in patients with multiple sclerosis and in vitro. Furthermore, our data suggest that this is at least in part as a result of the differential effects of DMF on Treg cells compared with conventional T cells.

IL-17 in inflammatory skin diseases psoriasis and hidradenitis suppurativa.

The skin is one of the most important organs in the body, providing integrity and acting as a barrier to exclude microbes, allergens and chemicals. However, chronic skin inflammation can result when barrier function is defective and immune responses are dysregulated or misdirected against harmless or self-antigens. During the last 15 years interleukin (IL)-17 cytokines have emerged as key players in multiple inflammatory disorders, and they appear to be especially prominent in skin inflammation. IL-17 cytokines produced by T cells and other cell types potently activate keratinocytes to promote inflammation in a feed-forward loop. Given this key pathogenic role of the IL-17 pathway in autoimmune and inflammatory disease, it has been the focus of intense efforts to target therapeutically. The inflammatory effects of IL-17 can be targeted directly by blocking the cytokine or its receptor, or indirectly by blocking cytokines upstream of IL-17-producing cells. Psoriasis has been the major success story for anti-IL-17 drugs, where they have proven more effective than in other indications. Hidradenitis suppurativa (HS) is another inflammatory skin disease which, despite carrying a higher burden than psoriasis, is poorly recognized and under-diagnosed, and current treatment options are inadequate. Recently, a key role for the IL-17 pathway in the pathogenesis of HS has emerged, prompting clinical trials with a variety of IL-17 inhibitors. In this review, we discuss the roles of IL-17A, IL-17F and IL-17C in psoriasis and HS and the strategies taken to target the IL-17 pathway therapeutically.

Dysregulation of the interleukin-17A pathway in endometrial tissue from women with unexplained infertility affects pregnancy outcome following assisted reproductive treatment.

STUDY QUESTION: Which transcriptomic alterations in mid-luteal endometrial scratch biopsies, taken prior to the assisted reproductive treatment (ART) treatment cycle are associated with unsuccessful pregnancy? SUMMARY ANSWER: Dysregulated interleukin-17 (IL-17) pathway components are demonstrated in women who fail to become pregnant after ART. WHAT IS KNOWN ALREADY: Implantation failure is now recognised as a critical factor in unexplained infertility and may be an important component of failed ART. STUDY DESIGN, SIZE, DURATION: Using a prospective longitudinal study design, 29 nulliparous women with unexplained infertility undergoing ART were recruited between October 2016 and February 2018. Mid-luteal stage endometrium and matched serum samples were collected, and patients underwent a single embryo transfer in the subsequent cycle. RNA-seq analysis of endometrial biopsies was performed on the discovery cohort (n = 20). PARTICIPANTS/MATERIALS, SETTING, METHODS: Gene set enrichment analysis of the differentially expressed genes (DEGs) was performed. Endometrium and serum were then prepared for IL-17A analysis by ELISA. MAIN RESULTS AND THE ROLE OF CHANCE: There were 204 differentially expressed protein-coding genes identified in tissue from women who became pregnant (n = 9) compared with tissue from women who failed to become pregnant (n = 11) (false discovery rate; P < 0.05). Of the 204 DEGs, 166 were decreased while 38 were increased in the pregnant compared to the non-pregnant groups. Gene set enrichment analysis of the DEGs identified an over-representation of IL-17 and Pl3K-Akt signalling pathways. All the DEGs within the IL-17 signalling pathway (MMP3, MMP1, IL1ß, LCN2, S100A9 and FOSL1) demonstrated decreased expression in the pregnant group. Serum IL-17 protein levels were increased in the non-pregnant discovery cohort (n = 11) and these findings were confirmed a validation cohort (n = 9). LIMITATIONS, REASONS FOR CAUTION: Limitations of our study include the cohort size and the lack of aneuploidy data for the embryos; however, all embryos transferred were single good or top-quality blastocysts. WIDER IMPLICATIONS OF THE FINDINGS: These findings demonstrate dysregulated IL-17 pathway components in women who fail to become pregnant after ART. Elevated serum levels of the pro-inflammatory cytokine IL-17 may predict failure of ART in women with unexplained infertility. Future trials of anti-IL-17 therapies in this cohort warrant further investigation. STUDY FUNDING/COMPETING INTEREST(S): Funding from the UCD Wellcome Institutional Strategic Support Fund, which was financed jointly by University College Dublin and the SFI-HRB-Wellcome Biomedical Research Partnership (ref 204844/Z/16/Z), is acknowledged. The authors have no competing interests. TRIAL REGISTRATION NUMBER: NA.

Hartmann's procedure versus intersphincteric abdominoperineal excision (HiP Study): a multicentre prospective cohort study.

AIM: In patients with low rectal cancer it is occasionally necessary to avoid a low coloanal anastomosis due to patient frailty or poor function. In such situations there are two alternative approaches: Hartmann's procedure (HP) or intersphincteric abdominoperineal excision (IAPE). There are few data to guide surgeons as to which of these two procedures is the safest. The aim of this study was to determine the surgical complication rates associated with each procedure. METHOD: This was a multicentre, nonrandomized prospective cohort study of patients undergoing either HP or IAPE. The primary objective was to determine surgical complication rates. Secondary objectives included length of stay, time to adjuvant therapy and quality of life at 90 days. RESULTS: One hundred and seventy nine patients were recruited between April 2016 and June 2019; approximately two thirds of patients underwent HP and one third IAPE. The overall complication rate was high in both groups (54% for the HP group and 52% for the IAPE group). Surgery-specific complication rates were also high, but not significantly different: 43% for HP and 48% for IAPE. The pelvic abscess rate in HP was 11% and was significantly higher in patients with a palpable staple line (15% vs 2%). There was a higher incidence of serious medical complications following IAPE (16% vs 5%), along with a reduction in 90-day quality of life scores. CONCLUSION: This is the largest prospective study to compare HP and IAPE in patients undergoing rectal cancer surgery where primary anastomosis is not deemed appropriate. With similar complication rates, these data support the ongoing use of either HP or IAPE in this patient group.

Ex vivo specimen MRI and pathology confirm a rectosigmoid mesenteric waist at the junction of the mesorectum and mesocolon.

AIM: Continuity of the mesentery has recently been established and may provide an anatomical basis for optimal colorectal resectional surgery. Preliminary data from operative specimen measurements suggest there is a tapering in the mesentery of the distal sigmoid. A mesenteric waist in this area may be a risk factor for local recurrence of colorectal cancer. This study aimed to investigate the anatomical characteristics of the mesentery at the colorectal junction. METHOD: In this cross-sectional study, 20 patients were recruited. After planned colorectal resection, the surgical specimens were scanned in a MRI system and subsequently dissected and photographed as per national pathology guidelines. Mesenteric surface area and linear measurements were compared between MRI and pathology to establish the presence and location of a mesenteric waist. RESULTS: Specimen analysis confirmed that a narrowing in the mesenteric surface area was consistently apparent at the rectosigmoid junction. Above the anterior peritoneal reflection, the surface area and posterior distance of the mesentery of the upper rectum initially decreased before increasing as the mesentery of the sigmoid colon. These anatomical properties created the appearance of a mesenteric 'waist' at the rectosigmoid junction. Using the anterior reflection as a reference landmark, the rectosigmoid waist occurred at a mean height of 23.6 and 21.7 mm on MRI and pathology, respectively. CONCLUSION: A rectosigmoid waist occurs at the junction of the mesorectum and mesocolon, and is a mesenteric landmark for the rectum that is present on both radiology and pathology.

Bio-based Algae Oil: an oxidation and structural analysis.

OBJECTIVE: In search of natural components, vegetal oils are increasingly becoming more popular in cosmetics. However, high oxidation instability, presence of potential allergens and synthetic anti-oxidants have limited their applications so far. Therefore, a need exists for a natural emollient with high oxidation stability. In this work, we report on a novel sustainably produced triglyceride containing primarily three monounsaturated oleic acid chains, dubbed 'Bio-Based Algae Oil' hereafter, as a natural emollient for cosmetic formulations. To produce Bio-Based Algae Oil, simple sugars are converted into triglyceride oils using microalgae fermentation with minimal environmental impact. METHODS: Bio-Based Algae Oil was compared to other commonly used triglyceride-based emollients in the skincare industry in terms of thermal/oxidation stability, composition and moisturizing properties. Oxidation stability of emollients was compared using Rancimat and pressurized differential scanning calorimetry (PDSC) techniques. Fatty acid composition of each oil was analysed using proton nuclear magnetic resonance (1 H-NMR) and gas chromatography (GC) techniques to correlate unsaturation level of each oil to its oxidation stability. We also conducted an in vivo moisturizing study in which skin hydration level of human subjects was compared before and after application of emollient up to 24 h. RESULTS: Results showed that Bio-Based Algae Oil was the most stable emollient in thermal and oxidation stability studies given its low unsaturation and high anti-oxidant content determined by 1 H-NMR and GC techniques. It also provided the highest skin hydration level when applied on skin demonstrating its efficacy as a moisturizing emollient in cosmetic formulations. CONCLUSIONS: Compositional analysis of Bio-Based Algae revealed that it is a triglyceride containing primarily three monounsaturated oleic acid chains with very low polyunsaturated fatty acid content resulting in high oxidation stability and consequently prolonged shelf-life. Given its sustainability, high oxidation stability and skin health benefits such as moisturization demonstrated during an in vivo study, we envision to utilize Bio-Based Algae Oil in many cosmetic formulations across skincare, suncare and bath and shower markets.

OBJECTIF: Dans la quête de composants naturels, les huiles végétales deviennent de plus en plus prisées en cosmétique. Toutefois, la forte instabilité à l'oxydation, la présence d'allergènes potentiels et d'antioxydants synthétiques ont contribué à la réduction de leurs demandes jusqu'ici. Par conséquent, il existe un besoin en émollient naturel doté d'une stabilité à l'oxydation élevée. Dans le cadre de ces travaux, nous présentons un nouveau triglycéride produit de manière durable contenant principalement trois chaînes d'acide oléique mono-insaturées, appelé « Huile d'algues d'origine biologique ¼ comme étant un émollient naturel pour les produits cosmétiques. Pour obtenir de l'Huile d'algues d'origine biologique, des sucres rapides sont transformés en huiles triglycérides par fermentation de microalgues avec un impact environnemental minimal. MÉTHODES: L'huile d'algues d'origine biologique a été comparée à d'autres émollients à base de triglycérides fréquemment utilisés dans l'industrie des soins de la peau en matière de stabilité thermique ou d'oxydation, de composition et de propriétés hydratantes. Stabilité thermique ou oxydation, composition et propriétés hydratantes. La stabilité à l'oxydation des émollients a été comparée grâce au Rancimat et à des techniques de calorimétrie différentielle à balayage haute pression (PDSC). La composition des acides gras de chaque huile a été analysée grâce aux techniques de résonance magnétique nucléaire du proton (1 H-NMR) et de chromatographie en phase gazeuse (CPG) afin de créer une corrélation entre le taux d'insaturation de chaque huile et sa stabilité à l'oxydation. Nous avons également procédé à une étude in vivo de l'hydratation au cours de laquelle le niveau d'hydratation de la peau des patients humains a été comparé avant et après l'utilisation de l'émollient sur une période allant jusqu'à 24 h. RÉSULTATS: Les résultats ont démontré que l'huile d'algues d'origine biologique était l'émollient le plus stable lors des études sur la stabilité thermique et la stabilité à l'oxydation, en raison de sa faible insaturation et de sa teneur élevée en antioxydants déterminés par les techniques 1 H-NMR et GC. Elle a également produit le taux d'hydratation de la peau le plus élévé, lorsqu'appliqué à la peau, ce qui démontre son efficacité comme émollient hydratant dans les produits cosmétiques. CONCLUSIONS: L'analyse de la composition de l'huile d'algues d'origine biologique a révélé qu'il s'agit d'un triglycéride contenant principalement trois chaînes d'acide oléique mono-insaturées avec une très faible teneur en acides gras polyinsaturés, ce qui entraîne une stabilité à l'oxydation élevée et par conséquent une durée de vie prolongée. Compte tenu de sa durabilité, sa stabilité à l'oxydation élevée et ses bienfaits pour la santé de la peau, notamment l'hydratation démontrée au cours d'une étude in vivo, nous envisageons d'utiliser l'huile d'algues d'origine biologique dans de nombreuses formulations cosmétiques présentes sur le marché des soins de la peau, des produits solaires et des bains et douches.

Not all abdominal masses after colorectal cancer surgery are malignant: intra-abdominal fibromatosis masquerading as recurrence.

AIM: Intra-abdominal fibromatosis is an unusual mesenchymal tumour that can be locally aggressive without any metastatic potential. Fibromatosis may simulate cancer recurrence on imaging surveillance for colorectal cancer follow-up. The optimal treatment of recurrent peritoneal malignancy is cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC). Confirmatory biopsy of lesions suspicious for colorectal cancer recurrence may not be feasible, thereby rendering surgery the safest option. Our aim was to determine the incidence of fibromatosis in a cohort of patients undergoing CRS and HIPEC for suspected colorectal cancer recurrence. METHODS: One hundred and seventy-one CRS and HIPEC cases were performed at our Peritoneal Malignancy Institute between February 2007 and October 2018 for colorectal peritoneal metastases and were included in a prospectively maintained database. RESULTS: A total of 49 (29%) of 171 cases were performed for primary colorectal cancer with peritoneal metastases, whereas 122 (71%) of 171 cases were performed for suspected colorectal cancer recurrence detected on surveillance imaging after primary colorectal cancer resection. On histological analysis of the resected specimen, five (4.1%) of 122 cases undergoing CRS and HIPEC for colorectal recurrence had fibromatosis. CONCLUSION: Fibromatosis can masquerade as colorectal cancer recurrence. In this series it occurred with an incidence of 4.1% among a cohort of patients undergoing CRS and HIPEC for probable recurrence. Surgical resection may be the only option to confirm the diagnosis and rule out malignancy.

Session 4: Trying to augment response with chemotherapy: a triumph of hope over experience?

As part of an approach to improve tumour regression and increase the proportion of patients with complete clinical and radiological response, Dr Perez reviews the methods and evidence base for augmenting therapy and thus augmenting response rates preoperatively. Much of the data reviewed were in the context of patients undergoing a watch-and-wait approach for rectal cancer after initial treatment with chemoradiotherapy.

Session 4: Shaping radiotherapy for rectal cancer: should this be personalized?

Preoperative radiotherapy continues to be widely used in patients with operable rectal cancer. However, the indications and goals for such treatment are evolving. Professor Marijnen reviews the historic and current evidence base for the use of preoperative neoadjuvant radiotherapy and the future challenges in tailoring the therapy according to the patients' needs and tumour stage.

Impact of ovarian metastases on survival in patients treated with cytoreductive surgery and hyperthermic intraperitoneal chemotherapy for peritoneal malignancy originating from appendiceal and colorectal cancer.

AIM: Ovarian metastases from gastrointestinal tract malignancies have been considered an ominous finding with poor prognosis. The aim of this project was to determine the impact on survival, and potential cure, when cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) are combined to treat peritoneal malignancy in women with Krukenberg tumours. METHOD: A retrospective analysis of prospectively collected data between January 2010 and July 2015. Female patients undergoing complete CRS (macroscopic tumour removal) and HIPEC for pseudomyxoma peritonei (PMP) of appendiceal origin, or colorectal peritoneal metastases (CPM) were included. Survival was estimated using the Kaplan-Meier method and survival rates compared using the log-rank test. RESULTS: In total, 889 patients underwent surgery for peritoneal malignancy, of whom 551 were female. Of these, 504/551 (91%) underwent complete CRS and HIPEC. Overall, 405/504 (80%) had at least one involved ovary removed either during CRS and HIPEC or at their index prereferral operation. Three hundred and fifty-two patients (87%) had an appendiceal tumour and 53 (13%) had CPM. At a median follow up of 40 months, overall survival (OS) did not differ significantly between patients with or without ovarian involvement in women with a primary low-grade appendiceal tumour or CPM. In women with high-grade primary appendiceal pathology, OS was significantly lower in patients with ovarian metastases compared with those without ovarian involvement. CONCLUSION: Women with ovarian metastases from low-grade appendiceal tumours or colorectal cancer treated with CRS and HIPEC have similar survival rates to patients without ovarian metastases. Long-term survival and cure is feasible in patients amenable to complete tumour removal.

Variations in the management of significant polyps and early colorectal cancer: results from a multicentre observational study of 383 patients.

AIM: The concept of significant polyps and early colorectal cancer (SPECC) encompasses complex polyps not amenable to routine snare polypectomy or where malignancy cannot be excluded. Surgical resection (SR) offers definitive treatment, but is overtreatment for the majority which are benign and amenable to less invasive endoscopic resection (ER). The aim of this study was to investigate variations in the management and outcomes of significant colorectal polyps. METHOD: This was a retrospective observational study of significant colorectal polyps, defined as nonpedunculated lesions of ≥ 20 mm size, diagnosed across nine UK hospitals in 2014. Inclusion criteria were endoscopically or histologically benign polyps at biopsy. RESULTS: A total of 383 patients were treated by primary ER (87.2%) or SR (12.8%). Overall, 108/383 (28%) polyps were detected in the Bowel Cancer Screening Programme (BCSP). Primary SR was associated with a significantly longer length of stay and major complications (P < 0.01). Of the ER polyps, 290/334 (86.8%) patients were treated without undergoing surgery. The commonest indication for secondary surgery was unexpected polyp cancer, and of these cases 60% had no residual cancer in the specimen. Incidence of unexpected cancer was 10.7% (n = 41) and was similar between ER and SR groups (P = 0.11). On multivariate analysis, a polyp size of > 30 mm and non-BCSP status were independent risk factors for primary SR [OR 2.51 (95% CI 1.08-5.82), P = 0.03]. CONCLUSION: ER is safe and feasible for treating significant colorectal polyps. Robust accreditation within the BCSP has led to improvements in management, with lower rates of SR compared with non-BCSP patients. Standardization, training in polyp assessment and treatment within a multidisciplinary team may help to select appropriate treatment strategies and improve outcomes.

A national methodology to quantify the diet of grazing dairy cows.

The unique rumen of dairy cows allows them to digest fibrous forages and feedstuffs. Surprisingly, to date few attempts have been made to develop national methods to gain an understanding on the make-up of a dairy cow's diet, despite the importance of milk production. Consumer interest is growing in purchasing milk based on the composition of the cows' diet and the time they spend grazing. The goal of this research was to develop such a methodology using the national farm survey of Ireland as a data source. The analysis was completed for a 3-yr period from 2013 to 2015 on a nationally representative sample of 275 to 318 dairy farms. Trained auditors carried out economic surveys on farms 3 to 4 times per annum. The auditors collected important additional information necessary to estimate the diet of cows including the length of the grazing season, monthly concentrate feeding, type of forage(s) conserved, and milk production. Annual cow intakes were calculated to meet net energy requirements for production, maintenance, activity, pregnancy, growth, and live weight change using survey data and published literature. Our analysis showed that the average annual cow feed intake on a fresh matter basis ranged from 22.7 t in 2013 to 24.8 t in 2015 and from 4.8 to 5 t on a dry matter basis for the same period. Forage, particularly pasture, was the largest component of the Irish cow diet, typically accounting for 96% of the diet on a fresh matter basis and 82% of dry matter intake over the 3 yr. Within the cows' forage diet, grazed pasture was the dominant component and on average contributed 74 to 77% to the average annual cow fresh matter diet over the period. The proportion of pasture in the annual cow diet as fed was also identified as a good indicator of the time cows spend grazing (e.g., coefficient of determination = 0.85). Monthly, forage was typically the main component of the cow diet, but the average contribution of concentrate was substantial for the early spring months of January and February (30 to 35% of dry matter intake). Grazed pasture was the dominant source of forage from March to October and usually contributed 95 to 97% of the diet as fed in the summer period. Overall, the national farm survey from 2013 to 2015 shows that Irish dairy farms are very reliant on forage, particularly pasture, regardless of whether it is reported on a dry matter basis or as fed. There is potential to replicate this methodology in any regions or nations where representative farm surveys are conducted.

Factors associated with profitability in pasture-based systems of milk production.

The global dairy industry needs to reappraise the systems of milk production that are operated at farm level with specific focus on enhancing technical efficiency and competitiveness of the sector. The objective of this study was to quantify the factors associated with costs of production, profitability, and pasture use, and the effects of pasture use on financial performance of dairy farms using an internationally recognized representative database over an 8-yr period (2008 to 2015) on pasture-based systems. To examine the associated effects of several farm system and management variables on specific performance measures, a series of multiple regression models were developed. Factors evaluated included pasture use [kg of dry matter/ha and stocking rate (livestock units/ha)], grazing season length, breeding season length, milk recording, herd size, dairy farm size (ha), farmer age, discussion group membership, proportion of purchased feed, protein %, fat %, kg of milk fat and protein per cow, kg of milk fat and protein per hectare, and capital investment in machinery, livestock, and buildings. Multiple regression analysis demonstrated costs of production per hectare differed by year, geographical location, soil type, level of pasture use, proportion of purchased feed, protein %, kg of fat and protein per cow, dairy farm size, breeding season length, and capital investment in machinery, livestock, and buildings per cow. The results of the analysis revealed that farm net profit per hectare was associated with pasture use per hectare, year, location, soil type, grazing season length, proportion of purchased feed, protein %, kg of fat and protein per cow, dairy farm size, and capital investment in machinery and buildings per cow. Pasture use per hectare was associated with year, location, soil type, stocking rate, dairy farm size, fat %, protein %, kg of fat and protein per cow, farmer age, capital investment in machinery and buildings per cow, breeding season length, and discussion group membership. On average, over the 8-yr period, each additional tonne of pasture dry matter used increased gross profit by €278 and net profit by €173 on dairy farms. Conversely, a 10% increase in the proportion of purchased feed in the diet resulted in a reduction in net profit per hectare by €97 and net profit by €207 per tonne of fat and protein. Results from this study, albeit in a quota limited environment, have demonstrated that the profitability of pasture-based dairy systems is significantly associated with the proportion of pasture used at the farm level, being cognizant of the levels of purchased feed.

The LOREC APE registry: operative technique, oncological outcome and perineal wound healing after abdominoperineal excision.

AIM: The Low Rectal Cancer Development programme (LOREC) perineal wound healing registry was developed to record data on abdominoperineal excision (APE) for rectal cancer in colorectal units in England between 2012 and 2014, to understand current practice in operative technique and results. METHOD: Surgeons wishing to participate received secure Web-based access to the registry. Data were collected on preoperative staging, neoadjuvant treatment, operative details, histopathology, early outcome and follow up at 12 months. RESULTS: Forty-two units entered 266 patients. Of these, 172 (65%) patients underwent extralevator APE (ELAPE) and 94 had non-ELAPE procedures. On preoperative staging, 64% were mrT3/4, and 67% received neoadjuvant treatment. For the ELAPE group the perineal wound was closed primarily with mesh in 55% of patients, without mesh in 15% and with a flap in 21%. For non-ELAPE procedures, 54% of wounds were closed primarily without mesh, 29% primarily with mesh and 5% by a flap. Wound breakdown occurred in 30% and 31% of patients in the ELAPE and non-ELAPE groups, respectively, and was more common after neoadjuvant radiotherapy. Donor-site complications occurred in 17% of patients treated with a flap. Perineal morbidity was recorded in 11% of patients at 12 months. On histopathology, the resection margin was positive in 13% of patients in the ELAPE group and in 4% of patients in the non-ELAPE group. CONCLUSION: The LOREC registry provides a picture of current APE practice in England. ELAPE was used in two-thirds of patients but does not appear to confer any additional morbidity. Primary closure with mesh appeared as effective as flap reconstruction. The prevalence of an involved resection margin was lower than reported in many historical series but still remains high in the ELAPE group.

A collaborative review of the current concepts and challenges of anastomotic leaks in colorectal surgery.

The reduction of the incidence, detection and treatment of anastomotic leakage (AL) continues to challenge the colorectal surgical community. AL is not consistently defined and reported in clinical studies, its occurrence is variably reported and its impact on longterm morbidity and health-care resources has received relatively little attention. Controversy continues regarding the best strategies to reduce the risk. Diagnostic tests lack sensitivity and specificity, resulting in delayed diagnosis and increased morbidity. Intra-operative fluorescence angiography has recently been introduced as a means of real-time assessment of anastomotic perfusion and preliminary evidence suggests that it may reduce the rate of AL. In addition, concepts are emerging about the role of the rectal mucosal microbiome in AL and the possible role of new prophylactic therapies. In January 2016 a meeting of expert colorectal surgeons and pathologists was held in London, UK, to identify the ongoing controversies surrounding AL in colorectal surgery. The outcome of the meeting is presented in the form of research challenges that need to be addressed.