SF-CORNER (splenic flexure colorectal cancer): an international survey of operative approaches and outcomes for cancers of the splenic flexure.

AIM: The optimum surgical approach to splenic flexure cancers (SFCs) remains uncertain. The aim of this survey was to explore the opinions of an international surgical community on the management and outcomes of SFC. METHOD: A questionnaire was constructed comprising five sections (information about respondents; definition and prognosis of SFC; operative approach; approach in specific scenarios; outcomes) and circulated through an international dissemination committee and social media. RESULTS: The survey received 576 responses over 4 weeks across 50 countries. There was no consensus regarding the definition of the splenic flexure, whilst the proportion of respondents who did and did not think that patients with SFC had a worse outcome was equal. The overall preferred operative approach was left hemicolectomy [203 (35.2%)], followed by segmental resection [167 (29%)], extended right hemicolectomy [126 (21.9%)] and subtotal colectomy [7 (12%)]. The stated pedicles for ligation varied between resection types and also within the same resection. One hundred and sixty-six (28.8%) respondents thought a segmental resection was associated with the worst survival and 190 (33%) thought it was associated with the best quality of life. CONCLUSION: This survey confirms a lack of consensus across all aspects SFC treatment. The differing approaches described are likely to represent different beliefs around the variable anatomy of this region and the associated lymphatic drainage. Future studies are required to address such inconsistencies and identify the optimum surgical strategy, whilst also incorporating quality-of-life metrics and patient-reported outcomes. A one-size-fits-all approach is probably not appropriate with SFC, and a more bespoke approach is required.

Evaluating the potential utility of three-dimensional printed models in preoperative planning and patient consent in gastrointestinal cancer surgery.

INTRODUCTION: The Future of Surgery report from the Royal College of Surgeons of England acknowledges the important role that three-dimensional imaging will play in support of personalised surgical interventions. One component of this is preoperative planning. We investigated surgeons' and patients' perceptions of this evolving technology. MATERIALS AND METHODS: Ethical approval was obtained. From a normal computed tomography scan, three-dimensional models of the stomach, pancreas and rectum were rendered and printed on an Ultimaker™ three-dimensional printer. Semi-structured interviews were performed with surgeons and patients to explore perceived model effectiveness and utility. Likert scales were used to grade responses (1 = strongly disagree; 10 = strongly agree) and qualitative responses recorded. RESULTS: A total of 26 surgeons (9 rectal, 9 oesophagogastric, 8 pancreatic) and 30 patients (median age 62 years, interquartile range, IQR, 68-72 years; 57% male) were recruited. Median surgeon scores were effectiveness for preoperative planning, 6 (IQR 3-7), authenticity, 5 (IQR 3-6), likability, 6 (IQR 4-7), promoting learning, 7 (IQR 5-8), utility, 6 (IQR 5-7) and helping patients, 7 (IQR 5-8). Median patient scores were usefulness to the surgeon, 8 (IQR 7-9), authenticity, 8 (IQR 6-8), likability, 8 (IQR 7-8), helping understanding of condition, 8 (IQR 8-9), helping understanding of surgery, 8 (IQR 7-9) and feeling uncomfortable, 1 (IQR 1-4). Median overall decisional conflict score (0 = no; 100 = high) was 22 (IQR 19-28) and decision effectiveness was 25 (IQR 19-30). DISCUSSION: Overall, patients and surgeons considered that three-dimensional printed models were effective and had potential utility in education and, to a lesser extent, preoperative planning. Patient decisional conflict and effectiveness scores were weighted towards certainty in decision making but had room for improvement, which three-dimensional models may help to facilitate.

Metformin as a radiosensitiser for pelvic malignancy: A systematic review of the literature.

BACKGROUND: The treatment of pelvic malignancies has continued to improve over recent years, with neoadjuvant radiotherapy often considered the gold standard to downstage disease. Radiosensitisers are routinely employed in an attempt to improve response of cancers to radiotherapy. Previous preclinical evidence has suggested a role for metformin, a commonly used drug for type 2 diabetes. METHOD: A literature search was performed for published full text articles using the PubMed, Cochrane and Scopus databases using the search criteria string 'Metformin' AND ('Radiosensitivity' OR 'radiosensitising' OR 'radiosensitising'). Additional papers were detected by scanning the references of relevant papers. Data were extracted from each study by two authors onto a dedicated proforma. The review was registered on the PROSPERO database (ID: CRD42020199066). RESULTS: A total of 242 papers were identified, 11 of which were included in this review; an additional 5 papers were obtained from reference searches. Metformin has been demonstrated to reduce cell-viability post-radiotherapy in both rectal and prostate cancer cell lines, with an enhanced effect in tumours with a p53 mutation and increased apoptosis post-radiotherapy for cervical cancer. Clinical trials demonstrate improved tumour and nodal downstaging and pCR rates for rectal cancer using metformin as a radiosensitiser. CONCLUSION: With an increasing understanding of the underlying mechanism of the effects on metformin prospective studies are required to assess the effect of routine use on cancer related outcomes. Progressive future studies may be better served by the use of predictive biomarker guided treatment to enable identification of the appropriate cohort to target.

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.

Does tamoxifen have a therapeutic role outside of breast cancer? A systematic review of the evidence.

INTRODUCTION: Tamoxifen is a widely used hormonal based therapy for breast cancer in the adjuvant and metastatic setting, prolonging overall and recurrence-free survival. There has been increasing interest in the potential for novel "off-target" effects of tamoxifen and its metabolite N-desmethyltamoxifen across a number of cancer types. We aim to review the current literature regarding the potential use of tamoxifen in other primary malignancies. METHOD: A qualitative systematic review was performed according to the PRISMA guidelines using pre-set search criteria across the PubMed, Cochrane and Scopus databases from 1985 to 2019. Additional results were generated from included papers references. RESULTS: A total of 324 papers were identified, of which 47 were included; a further 29 articles were obtained from additional referencing to give a total of 76 articles. Clinical trials have demonstrated benefits with the use of tamoxifen in isolation and combination, specifically in patients with advanced non-resectable malignancy, however results are not consistent across the literature. In vivo data consistently suggests that off target effects of tamoxifen are mediated through the ceramide pathway or through inhibition of protein kinase C (PKC). CONCLUSIONS: With increased focus upon the potential of repurposing drugs, tamoxifen may be a candidate for repurposing in the wider cancer setting. There is evidence to suggest that the ceramide or PKC pathway could act as a therapeutic target for tamoxifen or alternative chemotherapeutics and merits further investigation.

A systematic review and meta-analysis of baseline risk factors for the development of postoperative ileus in patients undergoing gastrointestinal surgery.

INTRODUCTION: Postoperative ileus occurs frequently following abdominal surgery. Identification of groups at high risk of developing ileus before surgery may allow targeted interventions. This review aimed to identify baseline risk factors for ileus. METHODS: A systematic review was conducted with reference to PRISMA and MOOSE guidelines. It was registered on PROSPERO (CRD42017068697). Searches of MEDLINE, EMBASE and CENTRAL were undertaken. Studies reporting baseline risk factors for the development of postoperative ileus based on cohort or trial data and published in English were eligible for inclusion. Dual screening of abstracts and full texts was undertaken. Independent dual extraction was performed. Bias assessment was undertaken using the quality in prognostic studies tool. Meta-analysis using a random effects model was undertaken where two or more studies assessed the same variable. FINDINGS: Searches identified 2,430 papers, of which 28 were included in qualitative analysis and 12 in quantitative analysis. Definitions and incidence of ileus varied between studies. No consistent significant effect was found for association between prior abdominal surgery, age, body mass index, medical comorbidities or smoking status. Male sex was associated with ileus on meta-analysis (odds ratio 1.12, 95% confidence interval 1.02-1.23), although this may reflect unmeasured factors. The literature shows inconsistent effects of baseline factors on the development of postoperative ileus. A large cohort study using consistent definitions of ileus and factors should be undertaken.

Sphingolipids and acid ceramidase as therapeutic targets in cancer therapy.

BACKGROUND: Sphingolipids have been shown to play a key part in cancer cell growth and death and have increasingly become the subject of novel anti-cancer therapies. Acid ceramidase, a sphingolipid enzyme, has an important role in the regulation of apoptosis. In this review we aim to assess the current evidence supporting the role of sphingolipids in cancer and the potential role that acid ceramidase may play in cancer treatment. METHODS: A literature search was performed for published full text articles using the PubMed, Cochrane and Scopus databases using the search criteria string "acid ceramidase", "sphingolipid", "cancer". Additional papers were detected by scanning the references of relevant papers. A summary of the evidence for each cancer subgroup was then formed. Given the nature of the data extracted, no meta-analysis was performed. RESULTS: Over expression of acid ceramidase has been demonstrated in a number of human cancers. In vitro data demonstrate that manipulation of acid ceramidase may present a useful therapeutic target. In the clinical setting, a number of drugs have been investigated with the ability to target acid ceramidase, with the most promising of those being small molecular inhibitors, such as LCL521. CONCLUSION: The role of the sphingolipid pathway in cancer is becoming very clearly established by promoting ceramide accumulation in response to cancer or cellular stress. Acid ceramidase is over expressed in a variety of cancers and has a role as a potential target for inhibition by novel specific inhibitors or off-target effects of traditional anti-cancer agents. Further work is required to develop acid ceramidase inhibitors safe for progression to clinical trials.

Awareness of surgical expenditure amongst UK trainees and consultants: A questionnaire study.

INTRODUCTION: Limited knowledge of surgical device and service costs restricts a surgeon's ability to make cost efficient choices and contribute to the efficiency savings required by the NHS to reduce the financial deficit. This study aims to assess how aware surgeons are of surgical equipment and regularly used services. METHODS: A single sided hard copy questionnaire asking for the estimate cost of 24 surgical devices/services was handed out to individuals at two separate UK annual conferences. Items and services which are regularly used and/or clinically significant were selected and, where possible, alternatives to those items were included for comparison. Participants were also asked for their grade and specialty. An estimate was deemed correct if it was within 20% of the actual cost. Planned subgroup analyses for grade and specialty were performed. RESULTS: The 143 participants consisted of 23 (16%) consultants, 39 (27%) registrars, 33 (23%) SHOs and 48 (34%) foundation doctors. Of the 95 participants who were SHO grade or more senior, 67 (71%) work within general surgery. Across all items, only 9.6% of estimates were correct. There was no statistically significant difference between training levels (consultant 11.5%, registrar 10.1%, SHO 8.6%, foundation 8.9%; p = 0.253). Participants were significantly less successful in correctly estimating the cost of high value (>£150 [USD $198; EUR €175]) items (8.5% vs. 11.1%); p = 0.011, and the cost of devices as compared to the cost of services (7.4% vs. 15.0%); p = 0.001. CONCLUSION: Surgeons across all grades and specialties have poor knowledge of device and service costs. It is important that this improves in order to allow surgeons to make a meaningful contribution to NHS efficiency savings by making informed decisions about their use of devices and services.

Evaluating unmet needs in patients undergoing surgery for colorectal cancer: a patient reported outcome measures study.

AIM: Patient reported outcome measures (PROMs) are self-reported measures of patients' health status or health-related quality of life at a single point in time. We aimed to evaluate the use of a colorectal PROM and conducted a focus group to further explore this and other unmet needs in our patient population treated surgically for colorectal cancer. METHOD: A multidisciplinary research group consisting of colorectal surgeons, nurse specialists, psychologists, sociologists and patient representatives devised a composite tool of new and existing outcome measures which was piloted in our local population (n = 35). Participants were subsequently invited to attend a semi-structured focus group during which the PROM was reviewed and an unmet needs analysis was performed. Thematic analysis of focus group transcripts was undertaken for emergent themes. RESULTS: Initial consensus was for a tool including the EQ-5D, Functional Assessment of Cancer Therapy - Colorectal (FACT-C), the distress thermometer, a validated measure of stigma, an unmet needs analysis, and questions assessing the psychological impact of cancer. Median and interquartile range values suggested that all metrics were discriminatory with the exception of FACT-C. All participants agreed that the tool was acceptable and reflected the current state of their health and emotions. Thematic analysis of focus group transcripts identified four major themes: physical symptoms, emotional response, information provision and coping mechanisms. CONCLUSION: Through expert consensus, local piloting and patient focus groups we have evaluated a novel PROM for colorectal cancer. Furthermore, through our direct engagement with patients we have identified several unmet needs which we are currently exploring within the clinical service.

Early anastomotic complications in colorectal surgery: a systematic review of techniques for endoscopic salvage.

BACKGROUND: Anastomotic complications following colorectal surgery are associated with significant morbidity and mortality. For patients in whom systemic sepsis is absent or well controlled, minimal access techniques, such as endoscopic therapies, are being increasingly employed to reduce the morbidity of surgical re-intervention. In this review, we aim to assess the utility of endoscopic management in the acute setting of colorectal anastomotic complications, focusing on anastomotic leak. METHOD: A literature search was performed for published full text articles using the PubMed, Cochrane and Scopus databases using the search criteria string "colorectal anastomotic ("leak" OR "bleed"), "endoscopy", endoscopic management". Additional papers were detected by scanning the references of relevant papers. Data were extracted from each study by two authors onto a dedicated pro-forma. Given the nature of the data extracted, no meta-analysis was performed. RESULTS: A total of 89 papers were identified, 16 of which were included in this review; an additional 14 papers were obtained from reference searches. In patients who are not physiologically compromised, there are promising data regarding the salvage rate of stents, over-the-scope endoscopic clips, vacuum therapy and fibrin glue in the early management of colorectal anastomotic leak. There is no consensus regarding the optimal approach, and data to assist the physician in patient selection are lacking. Whilst data on salvage (i.e. healing and avoidance of surgery) are well understood, no data on functional outcomes are reported. CONCLUSION: Endoscopic therapy in the management of stable patients with colorectal anastomotic leaks appears safe and in selected patients is associated with high rates of technical success. Challenges remain in selecting the most appropriate strategy, patient selection, and understanding the functional and long-term sequelae of this approach. Further evidence from large prospective cohort studies are needed to further evaluate the role of these novel strategies.

Systematic review of treatment intensification using novel agents for chemoradiotherapy in rectal cancer.

BACKGROUND: With the well established shift to neoadjuvant treatment for locally advanced rectal cancer, there is increasing focus on the use of radiosensitizers to improve the efficacy and tolerability of radiotherapy. There currently exist few randomized data exploring novel radiosensitizers to improve response and it is unclear what the clinical endpoints of such trials should be. METHODS: A qualitative systematic review was performed according to the PRISMA guidelines using preset search criteria across the PubMed, Cochrane and Scopus databases from 1990 to 2017. Additional results were generated from the reference lists of included papers. RESULTS: A total of 123 papers were identified, of which 37 were included; a further 60 articles were obtained from additional referencing to give a total of 97 articles. Neoadjuvant radiosensitization for locally advanced rectal cancer using fluoropyrimidine-based chemotherapy remains the standard of treatment. The oral derivative capecitabine has practical advantages over 5-fluorouracil, with equal efficacy, but the addition of a second chemotherapeutic agent has yet to show a consistent significant efficacy benefit in randomized clinical assessment. Preclinical and early-phase trials are progressing with promising novel agents, such as small molecular inhibitors and nanoparticles. CONCLUSION: Despite extensive research and promising preclinical studies, a definite further agent in addition to fluoropyrimidines that consistently improves response rate has yet to be found.

Proteomic profiling of rectal cancer reveals acid ceramidase is implicated in radiation response.

BACKGROUND: Neoadjuvant chemoradiotherapy (CRT) is used in locally advanced rectal cancer when tumours threaten the circumferential resection margin, with varying response to treatment. This experimental study aimed to identify significantly differentially expressed proteins between patients responding and not responding to CRT, and to validate any proteins of interest. METHODS: Mass spectrometry (with isobaric tagging for relative quantification) analysis of rectal cancers pre- and post-CRT, and at resection. Validation of proteins of interest was performed by assessing tissue microarray (TMA) immunohistochemistry expression in a further 111 patients with rectal cancer. RESULTS: Proteomic data are available via ProteomeXchange with identifier PXD008436. Reduced abundance of contributing peptide ions for acid ceramidase (AC) (log fold change -1.526, p = 1.17E-02) was observed in CRT responders. Differential expression of AC was confirmed upon analysis of the TMAs. Cancer site expression of AC in stromal cells from post-CRT resection specimens was observed to be relatively low in pathological complete response (p = 0.003), and relatively high with no response to CRT (p = 0.017). CONCLUSION: AC may be implicated in the response of rectal cancer to CRT. We propose its further assessment as a novel potential biomarker and therapeutic target. SIGNIFICANCE: There is a need for biomarkers to guide the use of chemoradiotherapy in rectal cancer, as none are in routine clinical use. We have determined acid ceramidase may have a role in radiation response, based on novel proteomic profiling and validation in a wider dataset using tissue microarrays. The ability to predict or improve response would positively select those patients who will derive benefit, prevent delays in the local and systemic management of disease in non-responders, and reduce morbidity associated with chemoradiotherapy.

Exome sequencing of synchronously resected primary colorectal tumours and colorectal liver metastases to inform oncosurgical management.

BACKGROUND: Next generation sequencing technology has facilitated mapping of the colorectal cancer genotype and furthered our understanding of metastogenesis. The aim of this study was to investigate for conserved and different mutations in the exomes of synchronously resected primary colorectal tumour and liver metastases. This information could potentially be utilised to guide the treatment of advanced disease with the help of biological information from the primary tumour. METHODS: We performed exome sequencing of synchronously resected primary colorectal cancer and colorectal liver metastases as well as normal colonic mucosa and liver parenchyma, from four patients who had received neo-adjuvant chemotherapy, at a depth of 50X using the Ion Proton platform. Raw data was mapped to the reference genome prior to variant calling, annotation and downstream analysis. RESULTS: Exome sequencing identified 585 non-synonymous missense single nucleotide variants (SNVs), of which 215 (36.8%) were unique to the primary tumour, 226 (38.6%) unique to the metastasis and 81 (13.8%) present in patient matched pairs. SNVs identified in the ErbB pathway appear to be concordant between primary and metastatic tumours. CONCLUSION: Only 13.8% of the metastatic exome can be predicted by the genotype of the primary tumour. We have demonstrated concordance of a number of SNVs in the ErbB pathway, which may inform selection of therapeutic agents in advanced colorectal cancer.

Evaluation of a novel tissue stabilization gel to facilitate clinical sampling for translational research in surgical trials.

BACKGROUND: The aim was to establish the feasibility of using a tissue stabilization gel (Allprotect™) as an alternative to liquid nitrogen to facilitate collection of clinical samples for translational research. METHODS: Tumour samples from patients undergoing surgery for primary or metastatic colorectal cancer were either snap-frozen in liquid nitrogen or stored in Allprotect™ under a number of different conditions. Sample integrity was compared across different storage conditions by assessing biomolecule stability and function. DNA quality was assessed spectrophotometrically and by KRas genotyping by pyrosequencing. Total RNA retrieval was determined by nanodrop indices/RNA integrity numbers, and quality assessed by reverse transcription-PCR for two representative genes (high-mobility group box 1, HMGB1; carboxylesterase 1, CES1) and two microRNAs (miR122 and let7d). Western blot analysis of HMGB1 and CES1 was used to confirm protein expression, and the metabolic conversion of irinotecan to its active metabolite, SN-38, was used to assess function. RESULTS: Under short-term storage conditions (up to 1 week) there was no apparent difference in quality between samples stored in Allprotect™ and those snap-frozen in liquid nitrogen. Some RNA degradation became apparent in tissue archived in Allprotect™ after 1 week, and protein degradation after 2 weeks. CONCLUSION: In hospitals that do not have access to liquid nitrogen and -80°C freezers, Allprotect™ provides a suitable alternative for the acquisition and stabilization of clinical samples. Storage proved satisfactory for up to 1 week, allowing transfer of samples without the need for specialized facilities. Surgical relevance Access to clinical material is a fundamental component of translational research that requires significant infrastructure (research personnel, liquid nitrogen, specialized storage facilities). The aim was to evaluate a new-to-market tissue stabilization gel (Allprotect™), which offers a simple solution to tissue preservation without the need for complex infrastructure. Allprotect™ offers comparable DNA, RNA and protein stabilization to tissue snap-frozen in liquid nitrogen for up to 1 week. Degradation of biomolecules beyond this highlights its role as a short-term tissue preservative. Allprotect™ has the potential to increase surgeon participation in translational research and surgical trials requiring tissue collection.

Implementation of a new tool to improve the efficacy and safety of surgical handovers.

AIMS: Compliance with European working time regulations in surgical practice has resulted in an increase in the number of clinicians caring for individual patients and subsequently an increase in the frequency of handovers. In 2007, the Royal College of Surgeons of England produced guidelines on the minimum data-set for 'safe handover'. This audit examined compliance with these guidelines before and after adopting a more detailed electronic handover 'template' with the intention of improving handover quality and patient safety. METHODS: Pre-existing surgical 'take' electronic handover sheets were reviewed daily for two weeks to assess compliance with published guidance. A new proforma was introduced, training delivered and compliance re-audited. χ2 analysis was performed to determine statistical significance. RESULTS: The handovers of 118 patients were audited before, and 114 after, the implementation of the new proforma. Name and responsible consultant were recorded in all cases. Age (52% vs. 85%, p=<0.01), location (77% vs. 95%, p=<0.01), admission date (0% vs. 39%, p=<0.01), medical history (82% vs. 94%, p=0.01), diagnosis (55% vs. 93%, p=<0.01) and management plan (81% vs. 97%, p=<0.01) showed a statistically significant improvement with the new proforma. Presenting complaint (93% vs. 98%) and investigation (90% vs. 90%) data remained good. Review frequency (5%vs.11%) and outstanding tasks (21% vs. 27%) were poorly documented. CONCLUSIONS: Significant improvement was seen in the completeness of information handed-over following the introduction of the new proforma with likely positive implications for patient safety and standard of care. Opportunity for improvement still remains however, and more specific focussed tuition for trainees is required.

The aetiology of delay to commencement of adjuvant chemotherapy following colorectal resection.

PURPOSE: Timely administration of adjuvant chemotherapy following colorectal resection is associated with improved outcome. We aim to assess the factors which are associated with delay to adjuvant chemotherapy in patients who underwent colorectal resection as part of an enhanced recovery protocol. METHOD: A univariate and multivariate analysis of patient data collected as part of a prospectively maintained database of colorectal cancer patients between 2007 and 2012. RESULTS: 166 patients underwent colorectal resection followed by adjuvant chemotherapy. Median postoperative hospital stay was 6 days, and time to commencement of adjuvant chemotherapy was 50 days. Longer inpatient stay correlated with increased time to adjuvant chemotherapy (P = 0.05). Factors found to be independently associated with duration of hospital stay and time to commencement of adjuvant chemotherapy included stoma formation (P = 0.032), anastaomotic leak (P = 0.027), and preoperative albumin (P = 0.027). The use of laparoscopic surgery was associated with shorter time to adjuvant chemotherapy but did not reach significance (P = 0.143). CONCLUSION: A number of independent variables associated with delay to adjuvant therapy previously not described have been identified. Further work may be required to elucidate the effect that these variables have on long-term outcome.

Outcome of colorectal cancer resection in octogenarians.

INTRODUCTION: Octogenarians constitute a rapidly growing segment of patients undergoing colorectal cancer resection, but their outcomes remain understudied and under-reported. Our aims were to analyse outcomes of octogenarian patients undergoing curative colorectal resections compared with a similar cohort 2 decades younger. METHODS: Data from a prospectively collected database of consecutive patients undergoing colorectal resection between 2004 and 2006 were analysed. Primary endpoints were 30-day mortality and morbidity. The secondary endpoint was long-term survival. RESULTS: Eighty-one consecutive patients aged >80 years and 61 patients aged 60 - 70 years undergoing elective and emergency resections were identified. In the octogenarian group, 75.3% of resections were elective compared with 78.0% in the younger cohort (p=0.9), with pelvic procedures accounting for 34.6% and 44.3%, respectively (p=0.34). The elderly had a significantly higher median CR-Possum (performance status) score than the younger cohort (18.0 v. 14.0; p=0.001). Permanent stoma rates were similar (22% for octogenarians v. 27% for younger patients; p=0.8), as was pathological stage (p=0.24). There was 1 death within 30 days after resection in each group. Median survival in the octogenarian cohort was 73 months compared with 74 months in the younger cohort, and 5-year survival rates were 53.1% and 66.0%, respectively (p=0.2, Mantel-Cox). CR-Possum score did not affect overall survival (p=0.711, Mantel-Cox), but a higher score correlated with more postoperative complications in both groups. CONCLUSIONS: Octogenarians have poor performance status, but can undergo resection with acceptable mortality and morbidity. Overall survival in the two age groups studied was similar, with poor performance status being associated with higher postoperative complications but no long-term difference in survival.

Management of iatrogenic recto-urethral fistula by transanal rectal flap advancement.

AIM: Recto-urethral fistulas are an uncommon, but devastating complication following rectal or urinary tract surgery. Repair is often difficult, and the optimal approach is unclear. We report our recent experience using an endorectal advancement flap. METHOD: A case note review of all patients undergoing repair of recto-urethral fistula in our institution was undertaken. Data on aetiology of the fistula, patient demographics, operative procedure and outcome both clinically and radiologically were extracted. RESULTS: Between 2002 and 2008, six transanal rectal advancement flaps in five patients were carried out. Four had undergone a laparoscopic radical prostatectomy, without any radiotherapy. Two types of fistula (type 1 associated with severe intra-abdominal sepsis and type 2 associated with localized sepsis) were found, with faecal diversion being less likely with the latter. Four (80%) patients underwent successful primary repair, with one patient requiring a second procedure. Postoperative cystography confirmed closure of the fistula in all five patients, and no recurrence has been observed at a mean follow-up time of 11 months. CONCLUSION: Rectal advancement flap is a simple, effective technique for iatrogenic recto-urethral fistula with minimal morbidity.

Pancreatic cancer cells overexpress gelsolin family-capping proteins, which contribute to their cell motility.

BACKGROUND: Previously, proteomic methods were applied to characterise differentially expressed proteins in microdissected pancreatic ductal adenocarcinoma cells. AIMS: To report that CapG and a related protein, gelsolin, which have established roles in cell motility, are overexpressed in metastatic pancreatic cancer; and to describe their pattern of expression in pancreatic cancer tissue and their effect on cell motility in pancreatic cancer cell lines. METHODS: CapG was identified by mass spectrometry and immunoblotting. CapG and gelsolin expression was assessed by immunohistochemical analysis on a pancreatic cancer tissue microarray and correlated with clinical and pathological parameters. CapG and gelsolin levels were reduced using RNA interface in Suit-2, Panc-1 and MiaPaCa-2 cells. Cell motility was assessed using modified Boyden chamber or wound-healing assays. RESULTS: Multiple isoforms of CapG were detected in pancreatic cancer tissue and cell lines. Immunohistochemical analysis of benign (n = 44 patients) and malignant (n = 69) pancreatic ductal cells showed significantly higher CapG staining intensity in nuclear (p<0.001) and cytoplasmic (p<0.001) compartments of malignant cells. Similarly, gelsolin immunostaining of benign (n = 24 patients) and malignant (n = 68 patients) pancreatic ductal cells showed higher expression in both compartments (both p<0.001). High nuclear CapG was associated with increased tumour size (p = 0.001). High nuclear gelsolin was associated with reduced survival (p = 0.01). Reduction of CapG or gelsolin expression in cell lines by RNAi was accompanied by significantly impaired motility. CONCLUSIONS: Up regulation of these actin-capping proteins in pancreatic cancer and their ability to modulate cell motility in vitro suggest their potentially important role in pancreatic cancer cell motility and consequently dissemination.