Faculty Bibliography

Klotho was first discovered as an anti-ageing protein linked to a number of age-related disease processes, including cardiovascular, renal, musculoskeletal, and neurodegenerative conditions. Emerging research has also demonstrated a potential therapeutic role for Klotho in cancer biology, which is perhaps unsurprising given that cancer and ageing share similar molecular hallmarks. In addition to functioning as a tumour suppressor in numerous solid tumours and haematological malignancies, Klotho represents a candidate therapeutic target for patients with these diseases, the majority of whom have limited treatment options. Here, we examine contemporary evidence evaluating the anti-neoplastic effects of Klotho and describe the modulation of downstream oncogenic signalling pathways, including Wnt/β-catenin, FGF, IGF1, PIK3K/AKT, TGFβ, and the Unfolded Protein Response. We also discuss possible approaches to developing therapeutic Klotho and consider technological advances that may facilitate the delivery of Klotho through gene therapy.

BACKGROUND:Polypoid endometriosis (PE) is a rare and uncommon variant of endometriosis that may present as a polypoid mass that simulates a malignant neoplasm. Typically, PE develops locally as a large benign pelvic mass. However, it may sometimes conceal a malignant disease in its context. CASE PRESENTATION/METHODS:A 53 years old, nulliparous lady, had been treated over a 10-year period for recurrent and symptomatic polypoid endometriosis of the pelvis. During this time, she underwent four surgical resections, the final one being a total pelvic exenteration, with histology demonstrating the presence of a rare myxoid low grade Endometrial Stromal Sarcoma (ESS) that had arisen in PE. CONCLUSION/CONCLUSIONS:PE is a rare variant growth pattern of endometriosis which may involve different pelvic organs and can mimic a malignant mass in the pelvis. It mostly affects women in their peri- or post-menopausal age and it is not always related to hormonal therapy. Malignances, such as Endometrial Stromal Sarcoma in this case, can arise in the context of PE and their diagnosis can be challenging. Surgical excision may constitute radical multi-organ resection, particularly for recurrent and symptomatic cases. However, the recurrence rates after surgery can be significant.

BACKGROUND:Healthcare systems and general surgeons are being challenged by the current pandemic. The European Association for Endoscopic Surgery (EAES) aimed to evaluate surgeons' experiences and perspectives, to identify gaps in knowledge, to record shortcomings in resources and to register research priorities. METHODS:An ad hoc web-based survey of EAES members and affiliates was developed by the EAES Research Committee. The questionnaire consisted of 69 items divided into the following sections: (Ι) demographics, (II) institutional burdens and management strategies, and (III) analysis of resource, knowledge, and evidence gaps. Descriptive statistics were summarized as frequencies, medians, ranges,, and interquartile ranges, as appropriate. RESULTS:The survey took place between March 25th and April 16th with a total of 550 surgeons from 79 countries. Eighty-one percent had to postpone elective cases or suspend their practice and 35% assumed roles not related to their primary expertise. One-fourth of respondents reported having encountered abdominal pathologies in COVID-19-positive patients, most frequently acute appendicitis (47% of respondents). The effect of protective measures in surgical or endoscopic procedures on infected patients, the effect of endoscopic surgery on infected patients, and the infectivity of positive patients undergoing laparoscopic surgery were prioritized as knowledge gaps and research priorities. CONCLUSIONS:Perspectives and priorities of EAES members in the era of the pandemic are hereto summarized. Research evidence is urgently needed to effectively respond to challenges arisen from the pandemic.

BACKGROUND:Digital rectal examination is a difficult examination to learn and teach because of limited opportunities for practice; however, the main challenge is that students and tutors cannot see the finger when it is palpating the anal canal and prostate gland inside the patients. OBJECTIVE:This paper presents an augmented reality system to be used with benchtop models commonly available in medical schools with the aim of addressing the problem of lack of visualization. The system enables visualization of the examining finger, as well as of the internal organs when performing digital rectal examinations. Magnetic tracking sensors are used to track the movement of the finger, and a pressure sensor is used to monitor the applied pressure. By overlaying a virtual finger on the real finger and a virtual model on the benchtop model, students can see through the examination and finger maneuvers. METHODS:The system was implemented in the Unity game engine (Unity Technologies) and uses a first-generation HoloLens (Microsoft Inc) as an augmented reality device. To evaluate the system, 19 participants (9 clinicians who routinely performed digital rectal examinations and 10 medical students) were asked to use the system and answer 12 questions regarding the usefulness of the system. RESULTS:The system showed the movement of an examining finger in real time with a frame rate of 60 fps on the HoloLens and accurately aligned the virtual and real models with a mean error of 3.9 mm. Users found the movement of the finger was realistic (mean 3.9, SD 1.2); moreover, they found the visualization of the finger and internal organs were useful for teaching, learning, and assessment of digital rectal examinations (finger: mean 4.1, SD 1.1; organs: mean 4.6, SD 0.8), mainly targeting a novice group. CONCLUSIONS:The proposed augmented reality system was designed to improve teaching and learning of digital rectal examination skills by providing visualization of the finger and internal organs. The initial user study proved its applicability and usefulness.

BACKGROUND:Better understanding of the impact of metachronous metastases in locally advanced and recurrent rectal cancer may improve decision-making. The aim of this study was to investigate factors influencing metachronous metastasis and its impact on survival in patients who have a beyond total mesorectal excision (bTME) operation. METHODS:This was a retrospective study of consecutive patients who had bTME surgery for locally advanced and recurrent rectal cancer at a tertiary referral centre between January 2006 and December 2016. The primary outcome was overall survival. Cox proportional hazards regression analyses were performed. The influence of metachronous metastases on survival was investigated. RESULTS:Of 220 included patients, 171 were treated for locally advanced primary tumours and 49 for recurrent rectal cancer. Some 90·0 per cent had a complete resection with negative margins. Median follow-up was 26·0 (range 1·5-119·6) months. The 5-year overall survival rate was 71·1 per cent. Local recurrence and metachronous metastasis rates were 11·8 and 22·2 per cent respectively. Patients with metachronous metastases had a worse overall survival than patients without metastases (median 52·9 months versus estimated mean 109·4 months respectively; hazard ratio (HR) 6·73, 95 per cent c.i. 3·23 to 14·00). Advancing pT category (HR 2·01, 1·35 to 2·98), pN category (HR 2·43, 1·65 to 3·59), vascular invasion (HR 2·20, 1·22 to 3·97) and increasing numbers of positive lymph nodes (HR 1·19, 1·07 to 1·16) increased the risk of metachronous metastasis. Nine of 17 patients (53 per cent) with curatively treated synchronous metastases at presentation developed metachronous metastases, compared with 40 of 203 (19·7 per cent) without synchronous metastases (P = 0·002). Corresponding median length of disease-free survival was 17·5 versus 90·8 months (P < 0·001). CONCLUSION/CONCLUSIONS:As metachronous metastases impact negatively on survival after bTME surgery, factors associated with metachronous metastases may serve as selection tools when determining suitability for treatment with curative intent.

INTRODUCTION/BACKGROUND:Acute lower gastrointestinal haemorrhage can potentially be life-threatening. We present a case of a massive rectal bleed which was managed successfully with a balloon tamponade device designed for upper gastrointestinal haemorrhage. PRESENTATION OF CASE/METHODS:A 75-year-old gentleman, with a history of human immunodeficiency virus and cirrhosis with portal hypertension, presented with bright red rectal bleeding. Investigations showed a low haemoglobin level (74 g/L) and deranged clotting. Oesophago-gastro-duodenoscopy demonstrated no fresh or altered blood. Flexible sigmoidoscopy revealed active bleeding from a varix within the anterior rectal wall 4 cm from the anal verge. Efforts to stop the bleeding, including endoscopic clips, adrenaline injection and rectal packing, were unsuccessful and the patient became haemodynamically unstable. A Sengstaken-Blakemore tube was inserted per rectum and the gastric balloon was inflated to tamponade the lower rectum. The oesophageal balloon was then inflated to hold the gastric balloon firmly in place. A computed tomography angiogram demonstrated no evidence of haemorrhage with balloon tamponade. After 36 h, the balloon was removed with no further episodes of bleeding. DISCUSSION/CONCLUSIONS:The application of a balloon tamponade device should be considered in the management algorithm for acute lower gastrointestinal bleed. Advantages include its rapid insertion, immediate results and ability to measure further bleeding after the catheter has been placed. CONCLUSION/CONCLUSIONS:Sengstaken-Blakemore tube per rectum may effectively control massive low rectal bleeding when alternative methods have been unsuccessful.

BACKGROUND:There are many options and little guiding evidence when choosing suture types with which to close the abdominal wall fascia. This network meta-analysis investigated the effect of suture materials on surgical site infection, hernia, wound dehiscence and sinus/fistula occurrence after abdominal surgery. The aim was to provide clarity on whether previous recommendations on suture choice could be followed with confidence. METHODS AND METHODS/METHODS:In February 2017, the Cochrane Central Register of Controlled Trials, Medline, EMBASE and Science Citation Index Expanded were searched for randomised controlled trials investigating the effect of suture choice on these four complications in closing the abdomen. A reference search of identified trials was performed. Prisma guidelines and the Cochrane risk of bias tool were followed in the data extraction and synthesis. Two review authors screened titles and abstracts of trials identified. A random effect model was used for the surgical site infection network based on the deviance information criterion statistics. RESULTS:Thirty-one trials were included (11,533 participants). No suture material reached the predetermined 90% probability threshold for determination of 'best treatment' for any outcome. Pairwise comparisons largely showed no differences between suture types for all outcomes measured. However, nylon demonstrated a reduction in the occurrence of incisional hernias with respect to two commonly used absorbable sutures: polyglycolic acid (odds ratio, OR 1.91; 95% confidence interval, CI, 1.01-3.63) and polyglyconate (OR 2.18; 95% CI 1.17-4.07). CONCLUSIONS:No suture type can be considered the 'best treatment' for the prevention of surgical site infection, hernia, wound dehiscence and sinus/fistula occurrence.

BACKGROUND:Colon cancer outcomes are now inferior to rectal cancer outcomes. The sigmoid colon is the most common site of colonic cancer. The aim of this review was to investigate the oncological outcomes for sigmoid cancer. METHODS:A systematic review and meta-analysis was performed. We included any study of the oncological outcomes for sigmoid cancer such as local recurrence, distant recurrence and disease free survival. A systematic search was conducted in Medline from inception to November 2016. Study quality was evaluated with the Newcastle-Ottawa Scale. The study was registered on PROSPERO (CRD42017069326). RESULTS:11.5%.). The median Newcastle-Ottawa score was 4 out of 9. R1 and R2 resections were excluded or not described in 16/17 studies. Two studies described R1 and R2 rates of 15-20%. CONCLUSION:The pooled local recurrence rate of sigmoid cancer of 10.5% is higher than contemporary rates of local recurrence of rectal cancer. A large number of papers fail to describe or include R1 resections of sigmoid cancer, which are frequently described as palliative.