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Objectives The Peritoneal Surface Oncology Group International (PSOGI) consensus subdivided pseudomyxoma peritonei (PMP) into four groups according to histopathological features. The aim of this paper is to report survival outcomes after cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) from a national referral centre and to correlate the PSOGI classification with survival. Methods A retrospective study of a prospectively maintained database was performed. Consecutive patients treated with CRS + HIPEC for PMP of appendiceal origin were included (September-2013 to December-2021). Pathological features of the peritoneal disease were used to classify patients into the four groups proposed by PSOGI. Survival analysis was performed to evaluate the correlation of pathology on overall survival (OS) and disease-free survival (DFS). Results Overall, 104 patients were identified; 29.6 % were reclassified as acellular mucin (AM), 43.9 % as low-grade mucinous carcinoma peritonei (LGMCP), 22.4 % as high-grade MCP (HGMCP) and 4.1 % as HGMCP with signet ring cells (HGMCP-SRC). Median PCI and rate of optimal cytoreduction were 19 and 82.7 %, respectively. Median OS and DFS were not reached, 5-year OS and DFS were 88.6(SD 0.04) % and 61.6(SD 0.06) %, respectively. Log-Rank test revealed significant differences in terms of OS and DFS across the different histological subgroups (p Conclusions Survival outcomes after CRS + HIPEC for PMP are excellent. The PSOGI pathological classification correlates with OS and DFS, but differences were not significant at multivariate analysis when adjusted for other prognostic factors.

Introduction Indocyanine green (ICG) quantification and assessment by machine learning (ML) could discriminate tissue types through perfusion characterisation, including delineation of malignancy. Here, we detail the important challenges overcome before effective clinical validation of such capability in a prospective patient series of quantitative fluorescence angiograms regarding primary and secondary colorectal neoplasia. Methods ICG perfusion videos from 50 patients (37 with benign (13) and malignant (24) rectal tumours and 13 with colorectal liver metastases) of between 2- and 15-min duration following intravenously administered ICG were formally studied (clinicaltrials.gov: NCT04220242). Video quality with respect to interpretative ML reliability was studied observing practical, technical and technological aspects of fluorescence signal acquisition. Investigated parameters included ICG dosing and administration, distance–intensity fluorescent signal variation, tissue and camera movement (including real-time camera tracking) as well as sampling issues with user-selected digital tissue biopsy. Attenuating strategies for the identified problems were developed, applied and evaluated. ML methods to classify extracted data, including datasets with interrupted time-series lengths with inference simulated data were also evaluated. Results Definable, remediable challenges arose across both rectal and liver cohorts. Varying ICG dose by tissue type was identified as an important feature of real-time fluorescence quantification. Multi-region sampling within a lesion mitigated representation issues whilst distance–intensity relationships, as well as movement-instability issues, were demonstrated and ameliorated with post-processing techniques including normalisation and smoothing of extracted time–fluorescence curves. ML methods (automated feature extraction and classification) enabled ML algorithms glean excellent pathological categorisation results (AUC-ROC > 0.9, 37 rectal lesions) with imputation proving a robust method of compensation for interrupted time-series data with duration discrepancies. Conclusion Purposeful clinical and data-processing protocols enable powerful pathological characterisation with existing clinical systems. Video analysis as shown can inform iterative and definitive clinical validation studies on how to close the translation gap between research applications and real-world, real-time clinical utility.

Surgical resection remains the cornerstone of ovarian cancer management. In 2017, the authors implemented a multi-disciplinary surgical team comprising gynecologic oncologists as well as colorectal, hepatobiliary, and upper gastrointestinal (GI) surgeons to increase gross macroscopic resection rates. This report aims to describe changes in complete cytoreduction rates and morbidity after the implementation of a multi-disciplinary surgical team comprising gynecologic oncologists as well as colorectal, hepatobiliary, and upper GI surgeons in a tertiary gynecologic oncology unit. The study used two cohorts. Cohort A was a retrospectively collated cohort from 2006 to 2015. Cohort B was a prospectively collated cohort of patients initiated in 2017. A multidisciplinary approach to preoperative medical optimization, intraoperative management, and postoperative care was implemented in 2017. The patients in cohort B with upper abdominal disease were offered primary cytoreduction with or without hyperthermic intraperitoneal chemotherapy (HIPEC). Before 2017, the patients with upper abdominal disease received neoadjuvant chemotherapy (cohort A). This study included 146 patients in cohort A (2006–2015) and 93 patients in cohort B (2017–2019) with stages 3 or 4 ovarian cancer. The overall complete macroscopic resection rate (CC0) increased from 58.9 in cohort A to 67.7% in cohort B. The rate of primary cytoreductive surgery (CRS) increased from 38 (55/146) in cohort A to 42% (39/93) in cohort B. The CC0 rate for the patients who underwent primary CRS increased from 49 in cohort A to 77% in cohort B. Major morbidity remained stable throughout both study periods (2006–2019). The study data demonstrate that implementation of a multidisciplinary team intraoperative approach and a meticulous approach to preoperative optimization resulted in significantly improved complete resection rates, particularly for women offered primary CRS.

With increasing subspecialised experience in radical cytoreductive surgery and intra-abdominal chemotherapy for peritoneal malignancy, outcomes have improved significantly in selected patients. The surgery and the treatment regimens are radical and therefore correct patient selection is critical. The radiologist plays a central role in this process by estimating, as precisely as possible, the pre-treatment disease burden. Because of the nature of the disease process, accurate staging is not an easy task. Tumour deposits may be very small and in locations where they are very difficult to detect. It must be acknowledged that no form of modern day imaging has the capability of detecting the smallest peritoneal nodules, which may only be visible to direct inspection or histopathological evaluation. Nonetheless, it behoves the radiologist to be as exact and precise as possible in the reporting of this disease process. This is both to select patients who are likely to benefit from radical treatment, and just as importantly, to identify patients who are unlikely to achieve adequate cytoreductive outcomes. In this review, we outline the patterns of spread of disease and the anatomic basis for this, as well as the essential aspects of reporting abdominal studies in this patient group. We provide an evidence-based update on the relative strengths and limitations of our available multimodality imaging techniques namely CT, MRI and positron emission tomography/CT.

Ileal pouch-anal anastomosis (IPAA) can restore bowel continuity for patients with ulcerative colitis (UC) who have needed total colectomy with end ileostomy. Internationally, this surgery is recommended for centralisation focussing reflection on Irish outcomes. Retrospective study examining patient outcomes after IPAA in our institution over a 15-year period using data from inflammatory bowel disease database, HIPE codes and clinical charts review between January 2002 and January 2018. Cohorts were analysed overall and in 5-year cohorts as well as by access modality of pouch operation. Contextualising Irish data were identified from published literature review. Thirty-four patients (average age 34.8, 21/64% male) had IPAA for UC locally with 64-month mean follow-up. Overall laparoscopic procedure rate was 39.4% (85% 2013–17) being associated with lower lengths of stay (10.6 ± 8 vs 12.7 ± 6.5 days open access). The mean total duration of ileostomy was 27.3 ± 22.5 months, being longest most recently and with an open index procedure. Overall pouchitis affected 53% (n = 18) with rates at 1, 5, 10 and 15 years being 17.6%, 38.2, 50.0% and 52.9%, respectively. Pouch failure rates at 1, 5 and 10 years were 2.9%, 11.8% and 17.6%. Outcomes were similar with other centres publishing from Ireland although none met modern criteria for high-volume practice. Overall outcomes and practice in this study are consistent with previously published studies on IPAA nationally and internationally. While acceptable, the opportunity from surgical centre collaboration outside of the National Cancer and Acute Surgery Strategies is to offer still better outcomes for our patients.

Highlights • Cisplatin chemotherapy is highly nephrotoxic and is a dose limiting side effect. • The OVIHIPEC-1 trial employed sodium thiosulphate (ST) as a renal protectant. • We analyse the implementation of HIPEC for EOC in a peritoneal malignancy centre. • One acute kidney injury (AKI) event was noted when ST was not used with HIPEC. • No AKI was observed when sodium thiosulphate was used with cisplatin at 100 mg/m2., Cisplatin based hyperthermic intraperitoneal chemotherapy (HIPEC) has been shown to prolong recurrence free and overall survival of women with ovarian cancer who have responded to neoadjuvant chemotherapy. The aim of this study was to assess the impact of cytoreductive surgery with or without the addition of HIPEC on renal function. Method This is a retrospective case-controlled study at a tertiary teaching hospital in Dublin, Ireland. All patients who had interval cytoreductive surgery (CRS) and HIPEC from October 2017 to October 2020 were included. A cohort of patients who had interval CRS without HIPEC were included as a control. Sodium thiosulphate (ST) was added to the HIPEC protocol in 2019. In order to assess the impact of ST as a renal protectant, renal function and post-operative outcomes were compared between the groups. Results Sixty patients who had interval CRS were included, thirty of whom received cisplatin-based HIPEC. Seven received cisplatin 50 mg/m2 without the addition of ST. Twenty three patients received cisplatin 100 mg/m2 and ST. There were no statistically differences in age, body mass index BMI, American society of anaesthesia score, estimated blood loss or peritoneal cancer index between the cohorts (p > 0.05). The only episode of acute kidney injury (AKI) was within the HIPEC cohort, after cisplatin 50 mg/m2 (without ST) and this was sustained at three months. In contrast, no patients within the CRS cohort or cisplatin 100 mg/m2 that received the addition of ST, sustained a renal injury and all had a creatinine within the normal range at three days post operatively. Conclusion The renal toxicity associated with cisplatin HIPEC and major abdominal surgery can be minimised with careful preoperative optimisation, intra operative fluid management and attention to renal function. The addition of sodium thiosulphate is a safe and effective method to minimise toxicity and should be added to any cisplatin HIPEC protocol.

Background: Cytoreductive surgery (CRS) and hyperthermic intra-peritoneal chemotherapy (HIPEC) is a complex surgical intervention with associated risks. Central venous catheter (CVC) line ...

Background Inflammatory markers are measured following colorectal surgery to detect postoperative complications. However, the association of these markers preoperatively with subsequent postoperative course has not yet been usefully studied. Aim The aim of this study is to assess the ability of preoperative C-reactive protein (CRP) and other inflammatory marker measurements in the prediction of postoperative morbidity after elective colorectal surgery. Methods This is a retrospective study which catalogs 218 patients undergoing elective, potentially curative surgery for colorectal neoplasia. Preoperative laboratory results of the full blood count (FBC), C-reactive protein (CRP) and carcinoembryonic antigen (CEA) were recorded. Multivariable analysis was performed to examine preoperative variables against 30-day postoperative complications by type and grade (Clavien-Dindo (CD)), adjusting for age, sex, BMI, smoking status, medical history, open versus laparoscopic operation, and tumor characteristics. Results Elevated preoperative CRP (≥ 5 mg/L) was significantly predictive of all-cause mortality, with an OR of 17.0 (p < 0.001) and was the strongest factor to predict a CD morbidity grade ≥ 3 (OR 41.9, p < 0.001). Other factors predictive of CD morbidity grade ≥ 3 included smoking, elevated preoperative platelet count and elevated preoperative neutrophil-lymphocyte ratio (OR 15.6, 8.6, and 6.3 respectively, all p < 0.05). CRP values above 5.5 mg/L were indicative of all-cause morbidity (AUC = 0.871), and values above 17.5 mg/L predicted severe complications (AUC = 0.934). Conclusions Elevated preoperative CRP predicts increased postoperative morbidity in this patient cohort. The results herein aid risk and resource stratification and encourage preoperative assessment of inflammatory propensity besides simple sepsis exclusion.

Introduction We assessed management of patients with de novo metastatic rectal cancer, referred for radiotherapy to the rectum, who were candidates for short-course radiotherapy (SCRT) and chemotherapy, followed by resection of all disease. We assessed surgical outcomes, overall survival (OS) and progression-free survival (PFS). Methods Retrospective review of patients meeting criteria: (i) treatment with SCRT to rectum; (ii) locally advanced primary rectal cancer; and (iii) resectable distant metastases at diagnosis. Data were collected from charts, correspondence and electronic patient records. OS and PFS were calculated using the Kaplan-Meier method. Results Between 2016 and 2020, 48 patients with stage IV rectal cancer at diagnosis were treated with SCRT. Only 15 patients (31%) had resectable metastatic disease and were intended for SCRT (25 Gy/5#), then chemotherapy, followed by resection of all sites of disease and are included in our study. 12 of the 15 surgical candidates (80%) had rectal surgery as planned, and 11 of the 15 (73%) had resection of the rectal primary and all metastatic disease. One patient had a pathological complete response (pCR), and 50% of surgical patients had a Mandard TRG of 1 or 2. Median PFS and OS for the 15 surgical candidates were 12.6 and 25.2 months, respectively, with a median FU of 21.2 months. Conclusion For this cohort of patients, our treatment paradigm is pragmatic and results in excellent pathological response. However, the effectiveness of this approach should be the subject of future prospective studies.

Cytoreductive Surgery (CRS) combined with hyperthermic intraperitoneal chemotherapy (HIPEC) is increasingly accepted as the optimal management of selected patients with peritoneal malignancy. There is limited published evidence on outcomes in older patients treated by this complex therapeutic strategy.A retrospective review of a prospective database of all patients who underwent CRS with HIPEC in a single institution over seven years. A comparative analysis of outcomes in patients under 65 undergoing CRS and HIPEC with patients ≥65 years was performed. The key endpoints were morbidity, mortality, reintervention rate and length of stay in the high dependency/intensive care (HDU/ICU) units.Overall, 245 patients underwent CRS and HIPEC during the study period, with 76/245 (31%) ≥65 years at the time of intervention. Tumour burden measured by the peritoneal carcinomatosis index (PCI) score was a median of 11 for both groups. Median length of hospital stay in the ≥65-year-old group was 14.5 days versus 13 days in the65-year-old group (∗p = 0.01). Patients aged ≥65-years spent a median of one more day in the critical care unit ∗(p = 0.001). Significant morbidity (Clavien-Dindo ≥ Grade IIIa) was higher in the ≥65-year than the65-year group (18.4% versus 11.2%). There were no perioperative deaths in the ≥65-year group.This study demonstrates higher perioperative major morbidity in ≥65-year group, but with low mortality in patients undergoing CRS/HIPEC for disseminated intraperitoneal malignancy. This increased morbidity does not translate into higher rates of re-interventions and highlights the importance of optimal patient selection.

Objective The aim of this paper is to report on changes in complete cytoreduction rates and morbidity following the implementation of a multi-disciplinary surgical team including gynaecological oncologists, colorectal and upper GI surgeons in a tertiary gynaecological oncology unit. In 2017 we implemented a multi-disciplinary surgical team including gynaecological oncologists, colorectal, hepatobiliary and upper GI surgeons to increase gross macroscopic resection rates. Methods Two cohorts were used. Cohort A was a retrospectively collated cohort from 2006–2015. Cohort B was a prospectively collated cohort of patients initiated in 2017. A multidisciplinary approach to preoperative medical optimisation, intra operative management and postoperative care was implemented in 2017. Patients in cohort B with upper abdominal disease were offered primary cytoreduction ± HIPEC. Prior to 2017 patients with upper abdominal disease received neoadjuvant chemotherapy. Results This study include 146 patients in cohort A (2006–2015) and 93 patients in cohort B (2017–2019) with stage III/IV ovarian cancer. The overall complete macroscopic resection rate (CC-0) increased from 58.9% in cohort A to 67.7% in cohort B. The rate of primary CRS increased from 38% (55/146) in cohort A to 42% (39/93) in cohort B. The CC-0 rate in those who had primary CRS increased from 49% in Cohort A to 77% in Cohort B. Major morbidity remained stable throughout both study periods. Conclusions Our data demonstrates that the implementation of multidisciplinary team intraoperative approach and a meticulous approach to preoperative optimisation has resulted in an significant improvement in complete resection rates particularly in women offered primary CRS.

TPS237 Background: Molecular characterisation of colorectal cancer (CRC) has demonstrated the regulatory role of epigenetic alterations, such as DNA methylation, in CRC tumorigenesis(1). Robust molecular profiling of CRC has the potential to provide critical diagnostic and prognostic information. The establishment of 4 consensus molecular subtypes (CMSs), developed initially for primary CRC tumours, resulted in the evolving framework for molecularly targeted interventions; the molecular genetic profile characterising mCRC is less well defined(3, 4). Previous pilot work identified a unique tumour-specific methylation sequence, at 376 sites within the DNA of mCRC cells(5). This study will assess whether this methylation sequence drives mCRC pathogenesis and underpins disease phenotype. The primary aim of this study is validation of the diagnostic utility of this novel enhancer signature and identification of key enhancers with the potential to direct targeted treatment development. Secondary aims include CRISPR knockdown library development targeting the enhancers in CRC cells in vitro, evaluating the impact of the knockdown on phenotype in vitro, and identifying the mechanisms by which methylation-sensitive enhancers regulate the mCRC phenotype. Methods: This is a retrospective, non-interventional, single-centre clinical study, including patients > 18 years, with (group A) de novo mCRC (n = 100), (group B) stage III colorectal cancer that subsequently relapsed (n = 100) or (group C) stage III colorectal cancer without radiological evidence of relapse at study enrolment (n = 100). Formalin-fixed, paraffin-embedded ( FFPE) tissue obtained at diagnosis will be analysed. Additionally, 50 stage III patients who have relapsed (group B) will have blood samples collected prospectively at time of consent to enable assessment for the presence of the methylation signature on ctDNA. The presence or absence of the novel methylation signature will be evaluated via the application of a targeted bisulfite sequencing panel consisting of the previously identified differentially methylated enhancer (DME) signature to both tissue and plasma samples; results will be correlated with conventional histological parameters, systemic therapy, and overall survival. Quantitative statistical analysis will be performed using SPSS with linear regression analysis for survival data. Ethical approval was obtained from the MMUH Institutional Review Board; reference 1/378/2188. This study is open and recruiting. Clinical trial information: 1/378/2188.

Multimodal therapy incorporating cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) improve survival for selected patients with colorectal peritoneal metastases (CPMs). Many countries have centralised management of these patients, aiming to improve outcomes. There is ongoing debate on the need for and complications associated with HIPEC administration. We report indications and outcomes after CRS/HIPEC treated in a national centre in the modern era. A retrospective review of all CPM patients who underwent CRS and HIPEC since the initiation of an Irish national program in 2013. The primary endpoint was the overall survival associated with CRS/HIPEC. During the study period (April 2013–June 2020), 123 patients proceeded to planned CRS/HIPEC for CPM. Median age was 58 (IQR 47–67) and 55 patients (44.7%) were male. In 65 patients (52.8%), CPM was synchronous. In 7/123 (5.8%), disease was unresectable. The median peritoneal cancer index (PCI) was 10 (IQR 5–17). Overall, 104/123 (84.5%) underwent a complete cytoreduction (CC0/CC1). Thirteen out of 123 (10.5%) patients also had a synchronous liver resection. Forty out of 123 (32.5%) patients had adverse pathological features (poorly differentiated or signet ring cells). The median survival in patients after CC0, CC1 and CC2/3 resection was 50, 18 and 11 months respectively (*p =

Surgical resection remains the cornerstone of ovarian cancer management. In 2017, the authors implemented a multi-disciplinary surgical team comprising gynecologic oncologists as well as colorectal, hepatobiliary, and upper gastrointestinal (GI) surgeons to increase gross macroscopic resection rates. This report aims to describe changes in complete cytoreduction rates and morbidity after the implementation of a multi-disciplinary surgical team comprising gynecologic oncologists as well as colorectal, hepatobiliary, and upper GI surgeons in a tertiary gynecologic oncology unit.The study used two cohorts. Cohort A was a retrospectively collated cohort from 2006 to 2015. Cohort B was a prospectively collated cohort of patients initiated in 2017. A multidisciplinary approach to preoperative medical optimization, intraoperative management, and postoperative care was implemented in 2017. The patients in cohort B with upper abdominal disease were offered primary cytoreduction with or without hyperthermic intraperitoneal chemotherapy (HIPEC). Before 2017, the patients with upper abdominal disease received neoadjuvant chemotherapy (cohort A).This study included 146 patients in cohort A (2006-2015) and 93 patients in cohort B (2017-2019) with stages 3 or 4 ovarian cancer. The overall complete macroscopic resection rate (CC0) increased from 58.9 in cohort A to 67.7% in cohort B. The rate of primary cytoreductive surgery (CRS) increased from 38 (55/146) in cohort A to 42% (39/93) in cohort B. The CC0 rate for the patients who underwent primary CRS increased from 49 in cohort A to 77% in cohort B. Major morbidity remained stable throughout both study periods (2006-2019).The study data demonstrate that implementation of a multidisciplinary team intraoperative approach and a meticulous approach to preoperative optimization resulted in significantly improved complete resection rates, particularly for women offered primary CRS.

Ileal pouch-anal anastomosis (IPAA) can restore bowel continuity for patients with ulcerative colitis (UC) who have needed total colectomy with end ileostomy. Internationally, this surgery is recommended for centralisation focussing reflection on Irish outcomes.Retrospective study examining patient outcomes after IPAA in our institution over a 15-year period using data from inflammatory bowel disease database, HIPE codes and clinical charts review between January 2002 and January 2018. Cohorts were analysed overall and in 5-year cohorts as well as by access modality of pouch operation. Contextualising Irish data were identified from published literature review.Thirty-four patients (average age 34.8, 21/64% male) had IPAA for UC locally with 64-month mean follow-up. Overall laparoscopic procedure rate was 39.4% (85% 2013-17) being associated with lower lengths of stay (10.6 ± 8 vs 12.7 ± 6.5 days open access). The mean total duration of ileostomy was 27.3 ± 22.5 months, being longest most recently and with an open index procedure. Overall pouchitis affected 53% (n = 18) with rates at 1, 5, 10 and 15 years being 17.6%, 38.2, 50.0% and 52.9%, respectively. Pouch failure rates at 1, 5 and 10 years were 2.9%, 11.8% and 17.6%. Outcomes were similar with other centres publishing from Ireland although none met modern criteria for high-volume practice.Overall outcomes and practice in this study are consistent with previously published studies on IPAA nationally and internationally. While acceptable, the opportunity from surgical centre collaboration outside of the National Cancer and Acute Surgery Strategies is to offer still better outcomes for our patients.

Introduction/Background HIPEC improves overall survival in patients with stage III epithelial ovarian cancer after neoadjuvant therapy compared to interval cytoreductive surgery (CRS) alone. The immediate impact of HIPEC on the systemic immune response has not been well characterised. We sought to document the impact of cisplatin-based HIPEC on the systemic immune response. Methodology Longitudinal analysis of neutrophil to lymphocyte ratio (NLR) and monocyte to neutrophil ratio (MLR) results in 22 age and stage matched patients with stage IIIc EOC were examined. Flow cytometric analysis (FACs) was performed on intra-operative PBMCs before and after HIPEC in 3 patients. Independent sample t test and one way ANOVA was used to analyse results using SPPS version 24. Results 9 patients had primary CRS, 8 had interval CRS+ cisplatin HPEC (50 mg/m2 at 40°C for 60 min), and 5 had interval CRS with no HIPEC. All patients had aggressive CRS and an CC0 resection. The interval CRS (no HIPEC) group had a significantly lower day 1 NLR compared to interval CRS HIPEC group (p=0.047). The NLR of all groups was similar by day 4. The MLR in the three groups was similar at all time points. FACs of peripheral CD3+ T Cells demonstrated that HIPEC increased circulating CD8+ T Cells and reduced expression of the immune checkpoint protein TIGIT (p Conclusion Cisplatin-based HIPEC causes an rapid and short-lived change in the systemic immune response. Our initial findings that HIPEC alters the expression of immune checkpoint proteins on CD8+ T cells suggests that further investigations of the combination of HIPEC and immunotherapy may be warranted. Disclosure Nothing to disclose.

The treatment of peritoneal surface malignancies ranges from palliative care to full cytoreductive surgery (CRS) and Heated Intraperitoneal Chemotherapy HIPEC. Ongoing monitoring of patient recruitment and volume is usually carried out through dedicated registries. With multiple registries available worldwide, we sought to investigate the nature, extent and value of existing worldwide CRS and HIPEC registries.METHODS: A questionnaire was sent out to all known major treatment centres. The questionnaire covers: general purpose of the registry; inclusion criteria in the registry; the date the registry was first established; volume of patients in the registry and description of the data fields in the registries. Finally, the population size of the catchment area of the registry was collected.RESULTS: 27 questionnaires where returned. National databases are established in northwest European countries. There are five international general databases. Most database collect data on patients who have undergone an attempt to CRS and HIPEC. Two registries collect data on all patients with peritoneal carcinomatosis regardless the treatment. Most registries are primarily used for tracking outcomes and complications. When correlating the number of cases of CRS and HIPEC that are performed to the catchment area of the various registry, a large variation in the number of performed procedures related to the overall population was noted, ranging from 1.3 to 57 patients/million year with an average of 15 patients/1 million year.CONCLUSION: CRS and HIPEC is a well-established treatment for peritoneal surface malignancies worldwide. However, the coverage as well as the registration of treatment procedures differs widely. The most striking difference is the proportion of HIPEC procedures per capita which ranges from 1.3 to 57 patients per million. This suggests either a difference in patient selection, lack of access to HIPEC centres or lack of appropriate data collection.

OBJECTIVE. The purpose of this article is to discuss the role of the radiologist in the treatment of peritoneal cancer, with focus placed on advanced treatment options and selection of patients with resectable disease for whom complete cytoreduction can be achieved. CONCLUSION. Peritoneal cancers traditionally have been associated with significant morbidity and universal mortality; however, the management of such cancers has evolved substantially. Advanced treatment options, including cytoreductive surgery and intraperitoneal chemotherapy, are associated with significantly improved long-term patient survival. To ensure that patients benefit from aggressive multimodality treatments, the radiologist plays a pivotal role in the multidisciplinary team to ensure careful patient selection, identifying individuals with resectable disease for whom complete cytoreduction can be achieved.

Background Cytoreductive Surgery (CRS) and Hyperthermic Intraperitoneal Chemotherapy (HIPEC) are considered standard of care for pseudomyxoma peritonei (PMP) and selected patients with colorectal peritoneal metastases (CPM) or peritoneal mesothelioma. A National Peritoneal Malignancy programme was established in Ireland (population of 4.5 million) in May 2013 with mentoring and support from the Peritoneal Malignancy Institute, Basingstoke UK. This study reviews the operative and oncological outcomes for the first 50 patients who underwent CRS and HIPEC in Ireland. Methods This is a retrospective review of all patients referred, and of the subset who underwent CRS and HIPEC, for peritoneal malignancy in Ireland between May 2013 and November 2015. Results During the study period, 130 patients were referred and 50 patients were selected for CRS and HIPEC. Three patients were found to have unresectable disease at laparotomy. Of the remaining 47 patients, eight had major tumour debulking. In total, 39 underwent complete cytoreduction and 45 received HIPEC. After a median follow-up of 12.7 months, 12 patients had developed further metastatic disease. The rates of complete cytoreduction, major complication (Clavien–Dindo III/IV) and operative mortality were 83%, 0% and 0%, respectively. 32% of patients experienced grade I/II complications. Conclusions We report the successful establishment of a national peritoneal malignancy programme. Mentoring from an experienced centre may have shortened the known learning curve evident by our encouraging outcomes. The follow-up period is short, however our early results are comparable with internationally reported figures.

Background Peritoneal mesothelioma (PM) is a rare primary neoplasm of the peritoneum with an increasing incidence worldwide. Cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC) has shown promise as a treatment strategy. A national PM multidisciplinary team (national PM MDT) video‐conference meeting was established in the UK and Ireland in March 2016, aiming to plan optimal treatment, record outcomes and provide evidence for the benefits of centralization. This article reports on the activities and outcomes of the first 2·5 years. Methods Between March 2016 and December 2018, patients with PM, referred to peritoneal malignancy centres in Basingstoke, Birmingham, Manchester and Dublin, were discussed by the national PM MDT via video‐conference. The MDT was composed of surgeons, radiologists, specialist nurses and pathologists. Patients were considered for CRS and HIPEC if considered fit for surgery and if radiological imaging suggested that complete surgical cytoreduction could be achieved. Morbidity and mortality following surgery were analysed. Survival analysis following MDT discussion was conducted. Results A total of 155 patients (M : F ratio 0·96) with a mean(s.d.) age of 57(17) years were discussed. To date, 22 (14·2 per cent) have had CRS and HIPEC; the median Peritoneal Cancer Index for the surgical group was 17·0. Complete cytoreduction was achieved in 19 patients. Clavien–Dindo grade I–II complications occurred in 16 patients; there was no grade III–IV morbidity or 30‐day in‐hospital mortality. The median follow‐up for the whole cohort was 18·7 months, and the 2‐year survival rate from time of first review at the national PM MDT was 68·3 per cent. Conclusion The centralized national PM MDT was effective at selecting patients suitable for CRS and HIPEC, reporting a good outcome from patient selection., The focus of this study was to demonstrate experience in understanding, managing and treating peritoneal mesothelioma, a rare disease, and explore how this was facilitated through the establishment of a national multidisciplinary team (MDT), a model that may be useful for other rare diseases. This centralized national peritoneal mesothelioma MDT was effective at selecting patients suitable for cytoreductive surgery and hyperthermic intraperitoneal chemotherapy, and advising on the optimal treatment strategy for patients unlikely to benefit from surgery. Peritoneal mesothelioma and national MDT

BackgroundThe primary treatment for advanced ovarian cancer is aggressive cytoreductive surgery (CRS), which is associated with considerable morbidity. The aim of this meta-analysis is to compare morbidity associated with primary CRS and secondary CRS for recurrent disease.MethodsA literature search was performed using Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines for publications reporting morbidity and mortality in patients undergoing CRS in primary and recurrent ovarian malignancy. Embase, Medline, Pubmed, Pubmed Central, clinicaltrials. gov and Cochrane databases were searched. Two independent reviewers applied inclusion and exclusion criteria to select included papers. A total of 215 citations were reviewed; 6 studies comprising 641 patients were selected for the analysis.ResultsResults were reported as mean differences or pooled odds ratios (OR) with 95 % confidence intervals (95 % CI). The overall morbidity rate was 38.4 %, and this did not differ between the two groups (p=0.97). This did not change when only Clavien-Dindo grade 3 and 4 morbidities were accounted for (14 % primary CRS, 15 % recurrent, p=0.83). Compared to primary CRS, secondary CRS was associated with a similar operative time (mean 400 min, I2=79 %, p=0.45), rate of bowel resection (I2=75 %, p=0.37) and transfusion requirements (MD – 0.7 L, I2=76 %, p=0.45). The mortality rate in both groups was too low to allow for meaningful meta-analysis, with four deaths in the group undergoing primary cytoreductive surgery (1.0 %) and two deaths in the group with recurrent disease (0.9 %).ConclusionsIn conclusion, secondary CRS for recurrent ovarian cancer is a safe and feasible option in carefully pre-selected patients with comparable morbidity to primary CRS.

Approximately one-third of patients with Crohn's disease have a distinct fibrostenosing phenotype predisposing them to recurrent intestinal stricture formation. The intestinal fibroblast was thought to play a critical role in the abnormal wound healing which ends in stricture formation. Recognising this, a laboratory-based research study was initiated at the Mater Misericordiae Hospital and University College Dublin with the aim of investigating the key steps in intestinal fibroblast-mediated stricture pathogenesis. An in vitro model was developed using cultured fibroblasts taken from sites of stricture in patients undergoing surgery. In summary, these fibroblasts were shown to carry multiple distinct pro-fibrotic phenotypic changes which may explain the abnormal wound healing and scar formation found at their sites of origin. This paper reviews that body of work, undertaken by series of surgical researchers and scientists, and driven by the insight, guidance and mentorship of Professor Ronan O'Connell.

Introduction Peritoneal metastases (PM) are predominantly seen as a manifestation of intra-abdominal malignancy such as colorectal or ovarian cancer. However, extra-abdominal primary cancer can also metastasise to the peritoneum. Population-based data on the incidence of PM from extra-abdominal cancer is lacking. This study aims to assess the patterns and survival of patients in Ireland with PM from extra-abdominal cancers. Methods The National Cancer Registry of Ireland database was interrogated to identify patients diagnosed with PM from extra-abdominal malignancy during the period 1994–2012. Patient demographics and tumour characteristics were analysed. Results 5791 patients were diagnosed with PM during the study period. Of these, 543 (9%) had an extra-abdominal primary malignancy. Breast (40.8%), lung (25.6%) and melanoma (9.3%) were the most common extra-abdominal cancers to develop PM. The majority of patients with peritoneal metastases of breast origin (75%) were diagnosed at a long interval (median interval 59.5 months; range = 1–485) from the diagnosis of the primary. The median survival from diagnosis of PM was 5.8 months compared with 22.6 months from diagnosis of stage IV disease without peritoneal involvement. Survival in patients with lung cancer and melanoma who developed PM was very poor and similar to that in patients with stage IV disease not involving the peritoneum. Conclusion This is the first population-based study to report the incidence of PM secondary to extra-abdominal malignancy. The most common primary cancers were melanoma, breast and lung cancer. Metastatic disease to the peritoneum was uniformly associated with a poor prognosis.

Peritoneal malignancy (PM) is predominantly metastatic spread from advanced gastrointestinal or gynaecological cancer. PM is generally considered incurable and therefore has rarely been the focus of novel therapeutic strategies. This study assessed patterns and survival outcomes for patients with PM in Ireland. The National Cancer Registry Ireland database was interrogated to identify patients diagnosed with PM during the period 1994–2012. Patient and tumour characteristics were retrieved and survival outcomes calculated. 5791 patients were diagnosed during the study period. Median age at diagnosis was 68 years; females accounted for 62%. The incidence increased annually from 228 in 1994 to 401 in 2012. Primary PM accounted for 3% of cases. Colorectal (22%), ovarian (16%) and gastric (13%) cancers accounted for the majority of cases of secondary PM. Almost 75% of patients had PM at initial presentation. Almost 40% of patients (n = 2274) underwent surgical intervention, while 44% (n = 2560) had tumour directed chemotherapy. The median survival (MS) in patients with secondary PM was 6.6 months, and did not improve significantly during the study period. Outcomes were best in patients with ovarian cancer (MS 15.9 months) and colorectal cancer (MS 14.3 months) and worst in patients with lung (MS 2.4 months) and pancreas (MS 1.9 months) cancers. This is the first population-based study from Ireland to report the incidence and outcomes for PM. PM is more common than previously reported and survival remains poor. These findings highlight the need for greater clinician awareness and the need to focus on new therapeutic approaches to improve patient outcomes.

Background The optimal treatment of peritoneal carcinomatosis of colorectal origin appears to be a combination of systemic chemotherapy and complete surgical cytoreduction with synchronous intraperitoneal chemotherapy. The aim of this study was to assess the feasibility of, and outcomes following, surgical treatment and systemic chemotherapy alone. Methods Prospectively collated data from the Erlangen Registry for Colorectal Cancer were analysed for patients presenting with peritoneal carcinomatosis of colorectal origin between 1990 and 2006. Operative and adjuvant treatment, along with details of postoperative morbidity, were evaluated and correlated with survival outcomes after 5 years. Results Some 125 patients underwent surgical resection for colorectal cancer and synchronous peritoneal carcinomatosis. Two-thirds also had non-peritoneal distant metastases. R0/R1 resection was possible in 24 (59 per cent) of 41 patients with peritoneal metastases alone, and in a further seven patients with both peritoneal and distant metastases (overall R0/R1 resection rate 24·8 per cent). In-hospital morbidity and mortality rates were 32·0 and 12·0 per cent respectively. Twenty-three of the 31 patients who underwent R0/R1 resection developed recurrent disease. Median survival for the entire group was 12 months. Following R0/R1 resection median survival was 25 months and the 5-year survival rate 22 per cent. Six (4·8 per cent) of the 125 patients survived for more than 5 years. Conclusion Complete resection of all metastatic disease was associated with improved survival and was possible in almost 60 per cent of patients with peritoneal metastases alone.

Introduction Anorectal melanoma is an uncommon disease constituting less than 3% of all melanomas. Due to its rarity, there are a lack of randomized control trials regarding appropriate management and current evidence is based mainly on retrospective studies. Methods In view of the controversial surgical treatment of anorectal melanoma, we review the most published literature in an attempt to elucidate its typical clinical features along with current thinking with respect to management approaches to this aggressive disease. Using the keywords "anorectal" and "malignant melanoma", a medline search of all articles in English was performed and the relevant articles procured. Additional references were retrieved by cross reference from key articles. Results Anorectal melanoma affects the elderly with a slight preponderance for females. It commonly presents disguised as benign disease with local bleeding or suspicion for haemorrhoidal disease. There is no convincing evidence to indicate that radical resection of primary anorectal melanoma is associated with improvement in local control or survival, and local excision is an acceptable treatment option. Conclusion Optimum management depends on several factors and the therapeutic goals should be to lengthen survival and preserve quality-of-life. Given that wide local excision is a more limited intervention with comparable survival it should be considered as the initial treatment choice. Unfortunately prognosis for patients with this disease remains poor despite choice of treatment strategy with overall five year disease-free survival less than twenty percent in most studies.

827 Background: The last 15 years have seen significant improvements in the outcomes of patients (pts) with CRC. More effective systemic therapy (Rx) and wider use of surgery (Sx) in stage IV disease (Dx) are key drivers of this. We evaluated the impact of intense surveillance in concert with greater use of metastasectomy and improved systemic Rx on CRC outcomes. Methods: This is a retrospective review of the clinical, radiologic and histological records for consecutive pts with CRC who were referred to the multi-disciplinary CRC team from 2003-2016. Pts with stage I/II Dx were included when referred for adjuvant Rx for high-risk features. We recorded pt characteristics, Rx received and outcomes. Survival was assessed using Kaplan-Meier analysis. Results: We identified 600 pts. Median age was 65 (22-97 years). 71.2% (n=427) of pts had left sided CRC and 25.7% (n=154) had right sided Dx. 211 pts (35.2%) had de novo metastatic Dx. 163 of 389 pts (41.9%) with stage II/III disease relapsed. Median Dx-free interval was 16 months. Of 163 relapses, 121 (74%) were detected by radiologic surveillance and 14 (9%) by rise in CEA. Symptomatic relapse occurred in 20 pts (12%). Median overall survival (OS) was significantly improved in pts with relapse detected by CT, PET/CT or CEA rise (54, 53 and 54 months respectively) vs pts with symptomatic relapse (4 months, p

Breast cancer is the most common cancer affecting European women and the leading cause of cancer-related death. A total of 15-20% of women who develop breast cancer have a family history and 5-10% a true genetic predisposition. The identification and screening of women at increased risk may allow early detection of breast cancer and improve prognosis. We established a family risk assessment clinic in May 2005 to assess and counsel women with a family history of breast cancer, to initiate surveillance, and to offer risk-reducing strategies for selected high-risk patients. Patients at medium or high risk of developing breast cancer according to NICE guidelines were accepted. Family history was determined by structured questionnaire and interview. Lifetime risk of developing breast cancer was calculated using Claus and Tyrer-Cuzick scoring. Risk of carrying a breast cancer-related gene mutation was calculated using the Manchester system. One thousand two hundred and forty-three patients have been referred. Ninety-two percent were at medium or high risk of developing breast cancer. Formal assessment of risk has been performed in 368 patients, 73% have a high lifetime risk of developing breast cancer, and 72% a Manchester score >or=16. BRCA1/2 mutations have been identified in 14 patients and breast cancer diagnosed in two. Our initial experience of family risk assessment has shown there to be a significant demand for this service. Identification of patients at increased risk of developing breast cancer allows us to provide individuals with accurate risk profiles, and enables patients to make informed choices regarding their follow-up and management

There are numerous factors which can affect the lymph node (LN) yield in colon cancer specimens. The aim of this paper was to identify both modifiable and non-modifiable factors that have been demonstrated to affect colonic resection specimen LN yield and to summarise the pertinent literature on these topics. A literature review of PubMed was performed to identify the potential factors which may influence the LN yield in colon cancer resection specimens. The terms used for the search were: LN, lymphadenectomy, LN yield, LN harvest, LN number, colon cancer and colorectal cancer. Both non-modifiable and modifiable factors were identified. The review identified fifteen non-surgical factors: (13 non-modifiable, 2 modifiable) which may influence LN yield. LN yield is frequently reduced in older, obese patients and those with male sex and increased in patients with right sided, large, and poorly differentiated tumours. Patient ethnicity and lower socioeconomic class may negatively influence LN yield. Pre-operative tumour tattooing appears to increase LN yield. There are many factors that potentially influence the LN yield, although the strength of the association between the two varies greatly. Perfecting oncological resection and pathological analysis remain the cornerstones to achieving good quality and quantity LN yields in patients with colon cancer.

BackgroundUltrastaging, by serial sectioning combined with immunohistochemical techniques, improves detection of lymph node micrometastases. Sentinel lymph node mapping and retrieval provides a representative node(s) to facilitate ultrastaging. The impact on staging of carcinoma of the colon and rectum in all series emphasizes the importance of this technique in cancer management. Now the challenge is to determine the biological relevance and prognostic implications.MethodsThe electronic literature (1966 to present) on sentinel node mapping in carcinoma of the colon and rectum was reviewed. Further references were obtained by cross-referencing from key articles.ResultsLymphatic mapping appears to be readily applicable to colorectal cancer and identifies those lymph nodes most likely to harbour metastases. Sentinel node mapping carries a false-negative rate of approximately 10 per cent in larger studies, but will also potentially upstage a proportion of patients from node negative to node positive following the detection of micrometastases. The prognostic implication of these micrometastases requires further evaluation.ConclusionFurther follow-up to assess the prognostic significance of micrometastases in colorectal cancer is required before the staging benefits of sentinel node mapping can have therapeutic implications.

The pre-operative staging of patients with peritoneal malignancy is challenging. Laparoscopy can improve the accuracy of staging compared with conventional imaging and may facilitate operative planning. This article is protected by copyright. All rights reserved.

Background Long-term results of both surgery and observation for patients with focal nodular hyperplasia (FNH) in a large single-center experience do not exist. Accordingly, the aim of this study was to compare long-term outcomes in patients with FNH who underwent either elective hepatectomy or observation alone. Methods A retrospective single-institution analysis of 185 patients with FNH, treated from 1990 to 2009, was performed. Results Seventy-eight patients underwent elective hepatectomy and 107 patients observation alone, with a median follow-up period of 113 months. There was no perioperative mortality. Postoperative complications were recorded in 12 patients, and 92% of patients reported symptomatic reductions. Among observation patients, 9 (13%) developed additional symptoms; tumor enlargement was seen in 3 patients (4%). Conclusions Elective liver resection for FNH is a safe procedure at high-volume centers. This single-center experience showed that 13% of observed patients had protracted symptoms. This justifies the therapeutic algorithm that elective surgery should be considered in symptomatic patients or in those with marked enlargement.

To assess the merits of currently available treatment options in the management of patients with low rectal cancer, a review of the medical literature pertaining to the operative and non-operative management of low rectal cancer was performed, with particular emphasis on sphincter preservation, oncological outcome, functional outcome, morbidity, quality of life, and patient preference. Low anterior resection (AR) is technically feasible in an increasing proportion of patients with low rectal cancer. The cost of sphincter preservation is the risk of morbidity and poor functional outcome in a significant proportion of patients. Transanal and endoscopic surgery are attractive options in selected patients that can provide satisfactory oncological outcomes while avoiding the morbidity and functional sequelae of open total mesorectal excision. In complete responders to neo-adjuvant chemoradiotherapy, a non-operative approach may prove to be an option. Abdominoperineal excision (APE) imposes a permanent stoma and is associated with significant incidence of perineal morbidity but avoids the risk of poor functional outcome following AR. Quality of life following AR and APE is comparable. Given the choice, most patients will choose AR over APE, however patients following APE positively appraise this option. In striving toward sphincter preservation the challenge is not only to achieve the best possible oncological outcome, but also to ensure that patients with low rectal cancer have realistic and accurate expectations of their treatment choice so that the best possible overall outcome can be obtained by each individual.

Background Fibroblasts isolated from strictures in Crohn's disease (CD) exhibit reduced responsiveness to stimulation with transforming growth factor (TGF) β1. TGF-β1, acting through the smad pathway, is critical to fibroblast-mediated intestinal fibrosis. The membrane glycoprotein, endoglin, is a negative regulator of TGF-β1. Methods Intestinal fibroblasts were cultured from seromuscular biopsies of patients undergoing intestinal resection for CD strictures or from control patients. Endoglin expression was assessed using confocal microscopy, flow cytometry and western blot. The effect of small interfering (si) RNA-mediated knockdown and plasmid-mediated overexpression of endoglin on fibroblast responsiveness to TGF-β1 was assessed by examining smad phosphorylation, smad binding element (SBE) promoter activity, connective tissue growth factor (CTGF) expression and ability to contract collagen. Results Crohn's stricture fibroblasts expressed increased constitutive cell-surface and whole-cell endoglin relative to control cells. Endoglin co-localized with filamentous actin. Fibroblasts treated with siRNA directed against endoglin exhibited enhanced TGF-β1-mediated smad-3 phosphorylation, and collagen contraction. Cells transfected with an endoglin plasmid did not respond to TGF-β1 by exhibiting SBE promoter activity or producing CTGF. Conclusion Fibroblasts from strictures in CD express increased constitutive endoglin. Endoglin is a negative regulator of TGF-β1 signalling in the intestinal fibroblast, modulating smad-3 phosphorylation, SBE promoter activity, CTGF production and collagen contraction.

Cytoreductive surgery combined with intraperitoneal chemotherapy can improve survival in appropriately selected patients with colorectal peritoneal metastases. Outcomes are best in those patients in whom a complete cytoreduction can be achieved. Unresectable disease is however encountered in approximately one-quarter of patients at laparotomy. The merits, or otherwise, of proceeding with an incomplete cytoreduction in this setting are unclear. We performed a review of published outcomes following incomplete cytoreduction for colorectal peritoneal metastases. Using the electronic databases, PubMed and MEDLINE, a systematic search of available literature published during the period January 1997 to September 2014 was conducted. Following application of exclusion criteria, 19 papers were identified and included in this review. These comprised fifteen case series, 3 case control studies and one randomised control trial. In the nineteen studies included in this review, 2790 patients underwent cytoreductive surgery with or without intraperitoneal chemotherapy for peritoneal metastases of colorectal origin. Of these, 1732 (62%) underwent a complete cytoreduction while 986 (35%) patients underwent an incomplete cytoreduction. Median survival in the complete cytoreduction group ranged from 11 to 62 mo while survival in the latter group ranged from 2.4 to 32 mo. Of the 986 patients with an incomplete cytoreduction, 331 patients received intraperitoneal chemotherapy and survival in this cohort ranged from 4.5 to 32 mo. An incomplete cytoreduction, with or without intraperitoneal chemotherapy, does not appear to confer a survival benefit. The limited available data points to a palliative benefit in a subset of patients. In the absence of high quality data, the decision as to whether or not to proceed with surgery should be made on an individual patient basis.

Introduction Over one-third of patients with Crohn's disease (CD) will develop an intestinal stricture and the great majority of these will require at least one surgical procedure. While the pathogenesis of inflammation in CD has been extensively investigated, knowledge of stricture pathogenesis remains limited. The aim of this review is to discuss the current understanding of fibrogenesis in CD and to outline potential directions in research and therapeutics. Methods The electronic literature (January 1966 to May 2006) on CD-associated fibrosis was reviewed. Further references were obtained by cross-referencing from key articles. Results CD-associated fibrosis results from chronic transmural inflammation and a complex interplay among intestinal mesenchymal cells, cytokines, and local inflammatory cells. The fibroblast is the key cell type mediating stricture formation. The cytoarchitecure of the bowel wall is altered with disruption of the muscularis mucosa, thickening of the muscularis propria, and deposition of collagen throughout. The cytokine TGF-beta appears critical in this process, acting to increase growth factor and extracellular matrix (ECM) production and dysregulate ECM turnover. Potential therapeutic interventions are likely to concentrate on modulating down-stream targets of TGF-beta. Conclusions Greater understanding of the biology of fibrostenosis is likely to yield significant advances in our ability to care for patients with stricturing CD. Potential dividends of this approach include identification of novel therapeutic targets and biomarkers useful for prognostication and therapeutic monitoring.