Metformin is a metabolic modulator and radiosensitiser in rectal cancer.

Resistance to neoadjuvant chemoradiation therapy, is a major challenge in the management of rectal cancer. Increasing evidence supports a role for altered energy metabolism in the resistance of tumours to anti-cancer therapy, suggesting that targeting tumour metabolism may have potential as a novel therapeutic strategy to boost treatment response. In this study, the impact of metformin on the radiosensitivity of colorectal cancer cells, and the potential mechanisms of action of metformin-mediated radiosensitisation were investigated. Metformin treatment was demonstrated to significantly radiosensitise both radiosensitive and radioresistant colorectal cancer cells in vitro. Transcriptomic and functional analysis demonstrated metformin-mediated alterations to energy metabolism, mitochondrial function, cell cycle distribution and progression, cell death and antioxidant levels in colorectal cancer cells. Using ex vivo models, metformin treatment significantly inhibited oxidative phosphorylation and glycolysis in treatment naïve rectal cancer biopsies, without affecting the real-time metabolic profile of non-cancer rectal tissue. Importantly, metformin treatment differentially altered the protein secretome of rectal cancer tissue when compared to non-cancer rectal tissue. Together these data highlight the potential utility of metformin as an anti-metabolic radiosensitiser in rectal cancer.

Attitudes and access of Irish general surgery trainees to robotic surgical training.

Background: Although the use of robotic-assisted surgery is now mainstream for procedures such as robotic prostatectomy and hysterectomy, its role in general surgery is less well established. Access to training in robotics for general surgery trainees in the Republic of Ireland is variable. Further, there are no data on specific attitudes of Irish trainees toward the role of robotics. We aimed to establish attitudes of Irish general surgery trainees toward the perceived utility of robotic surgery as well as access and satisfaction with training. Methods: A survey was disseminated to trainees in the Republic of Ireland enrolled in a General Surgery training scheme via email and social media. Data collected included stage of training, intended subspecialty, interest in developing robotic skills, previous exposure to robotic surgery, satisfaction with current access to robotic training, and opinion on formally incorporating training in robotics into the general surgery curriculum. Results: The response rate was 53.8%. Of these, 83% reported interest in training in robotics and 66% anticipated using the technology regularly in consultant practice. Previous exposure to robotic-assisted surgery was significantly predictive of interest in developing the skillset (P = .014). More than 71% of trainees reported that they were not satisfied with access to robotic training. Of those satisfied with access, 40% felt there was a role for incorporating robotic training into the curriculum compared to 68% of those dissatisfied. Conclusion: Irish general surgery trainees perceive robotic-assisted surgery to be highly relevant to their future practice. There is an unmet need to provide additional training in the skillset.

Robotic versus laparoscopic anterior resections for rectal and rectosigmoid cancer: an institutional experience.

INTRODUCTION: Colorectal surgery has evolved with the advent of laparoscopic techniques and now robotic-assisted surgery. There is significant literature supporting the use of laparoscopic techniques over open surgery with evidence of enhanced post-operative recovery, reduced use of opioids, smaller incisions and equivalent oncological outcomes. Robotic minimally invasive surgery addresses some of the limitations of laparoscopic surgery, providing surgical precision and improvements in perception and dexterity with a resulting decrease in tissue damage. METHODS: We retrospectively reviewed the medical records of patients who underwent robotic-assisted anterior resection for cancer of the rectum or rectosigmoid junction in our institution since our robotic programme began in 2017. Patient demographics were identified via electronic databases and patient charts. A matched cohort of laparoscopic cases was identified. RESULTS: A total of 51 consecutive robotic-assisted anterior resections were identified and case matched with laparoscopic resections for comparison. Robotic-assisted surgery was associated with a shorter length of stay (p = 0.04), reduced initial post-operative analgesia requirements (p < 0.01) and no significant difference in time to bowel movement or stoma functioning (p = 0.84). All patients had an R0 resection, and there was no statistical difference in lymph node yield between the groups (p = 0.14). Robotic surgery was associated with a longer operative duration (p < 0.001). CONCLUSION: In this early experience, robotic surgery has proven feasible and safe and is comparable to laparoscopic surgery in terms of completeness of resection and recovery. As costs and operating times decline and as technology progresses, robotic surgery may one day replace traditional laparoscopic techniques.

Diffuse large B-cell lymphoma of the rectum in a patient with Crohn's disease.

A 62-year-old man presented to our institute with diarrhoea and dysuria on a background of subtotal colectomy and end ileostomy and biological therapy for Crohn's disease. He was diagnosed with urinary tract infection and acute kidney injury (AKI). Renal ultrasound suggested left hydronephrosis, with renal protocol computed tomography (CT) showing a large pelvic mass. Magnetic resonance imaging (MRI) of the pelvis demonstrated a rectal tumour invading the bladder and compressing both ureters. He underwent cystoscopy, flexible sigmoidoscopy and positron emission tomography-CT and was diagnosed with stage IV non-Hodgkin's diffuse large B-cell lymphoma. He was treated primarily with rituximab, cyclophosphamide, hydroxydaunomycin, oncovin and prednisolone chemotherapy regimen. He had ongoing urosepsis before admission for pelvic exenteration. He underwent cystoprostatectomy, excision of rectal stump and formation of ileal conduit. Histology showed no signs of residual malignancy. One year later, the patient was admitted to the intensive care unit with aspiration pneumonia, urosepsis and AKI. Despite maximal therapy, he developed multiorgan failure and passed away.

Safe adoption of robotic colorectal surgery using structured training: early Irish experience.

Robotic surgery enhances the precision of minimally invasive surgery through improved three-dimensional views and articulated instruments. There has been increasing interest in adopting this technology to colorectal surgery and this has recently been introduced to the Irish health system. This paper gives an account of our early institutional experience with adoption of robotic colorectal surgery using structured training. Analysis was conducted of a prospectively maintained database of our first 55 consecutive robotic colorectal cases, performed by four colorectal surgeons, each at the beginning of his robotic surgery experience, using the Da Vinci Si® system and undergoing training as per the European Academy of Robotic Colorectal Surgery (EARCS) programme. Overall surgical and oncological outcomes were interrogated. Fifty-five patients underwent robotic surgery between January 2017 and January 2018, M:F 34:21, median age (range) 60 (35-87) years. Thirty-three patients had colorectal cancer and 22 had benign pathologies. Eleven rectal cancer patients had neoadjuvant chemoradiotherapy. BMI was > 30 in 21.8% of patients and 56.4% of patients had previous abdominal surgery. Operative procedures performed were low anterior resection (n = 19), sigmoid colectomy (n = 9), right colectomy (n = 22), ventral mesh rectopexy (n = 3), abdominoperineal resection (n = 1) and reversal of Hartmann's procedure (n = 1). Median blood loss was 40 ml (range 0-400). Mean operative time (minutes) was 233 (SD 79) for right colectomy and 368 (SD 105) for anterior resection. Median length of hospital stay was 6 days (IQR 5-7). There was no 30-day mortality, intraoperative complications, conversion to laparoscopic or open, or anastomotic leakage. Median lymph nodes harvest was 15 in non-neoadjuvant cases (range 7-23) and 8 in neoadjuvant cases (2-14). Our early results demonstrate that colorectal robotic surgery can be adopted safely for both benign and neoplastic conditions using a structured training programme without compromising clinical or oncological outcomes. The early learning curve can be time intensive.

Development and evaluation of a simulator-based laparoscopic training program for surgical novices.

BACKGROUND: The use of simulation to train novice surgeons in laparoscopic skills is becoming increasingly popular. To maximize benefit from simulation, training needs to be delivered and assessed in a structured manner. This study aimed to define performance goals, demonstrate construct validity of the training program, and evaluate whether novice surgeons could reach the preset performance goals. METHODS: Nine expert laparoscopic surgeons established performance goals for three basic modules of an augmented-reality laparoscopic simulator. The three laparoscopic modules were used by 40 novice surgeons and 40 surgical trainees (postgraduate years [PGYs] 1-4). The performance outcomes were analyzed across the different groups (novice, PGYs 1 and 2, PGYs 3 and 4, expert) to determine construct validity. Then 26 recruited novices trained on the three modules with the aim of reaching the performance goals. RESULTS: The results demonstrated a significant difference in performance between all levels of experience for time (p < 0.001), motion analysis (p < 0.001), and error score (p < 0.001), thus demonstrating construct validity. All 26 novice surgeons significantly improved in performance with repetition for the metrics of time (p < 0.001) and motion analysis (p < 0.001). For two of the modules, the proficiency goals were reached in fewer than 10 trials by 80% of the study participants. CONCLUSION: Basic skills in laparoscopic surgery can be learned and improved using proficiency-based simulation training. It is possible for novice surgeons to achieve predefined performance goals in a reasonable time frame.

Laparoscopic surgery for rectal cancer: a single-centre experience of 120 cases.

INTRODUCTION: For colorectal surgeons, laparoscopic rectal cancer surgery poses a new challenge. The defence of the questionable oncological safety tempered by the impracticality of the long learning curve is rapidly fading. As a unit specialising in minimally invasive surgery, we have routinely undertaken rectal cancer surgery laparoscopically since 2005. METHODS: Patients undergoing surgery for rectal cancer between June 2005 and February 2010 were retrospectively reviewed from a prospectively maintained colorectal cancer database. RESULTS: One hundred and thirty patients underwent surgery for rectal cancer during the study period. One hundred and twenty patients had a laparoscopic resection, six were converted to open (conversion rate 5%) and 10 had a planned primary open procedure. Fifty four were low rectal tumours and 76 were upper rectal tumours. One hundred and thirteen patients had an anterior resection (87%), 17 patients an abdomino-perineal resection (13%) and 62 of the 130 patients (47.6%) had neoadjuvant radiotherapy. The median lymph node retrieval rate was 12 (9-14), five patients (3.8%) had a positive circumferential margin and the clinical anastomotic leak rate was 3.8% (n = 5 patients). There was no significant difference in the stated parameters for neoadjuvant versus non-neoadjuvant patients and for upper versus lower rectal tumours. Ninety three percent of mesorectal excision specimens were complete on pathological assessment. CONCLUSIONS: During the study period, 92% of rectal cancers underwent a laparoscopic resection with low rates of morbidity and acceptable short-term oncological outcomes. This data supports the view that laparoscopic surgery for rectal cancer can be safely delivered in mid-volume centres by surgeons who have completed the learning curve for laparoscopic colorectal surgery.

Laparoscopic resection for low rectal cancer: evaluation of oncological efficacy.

INTRODUCTION: Laparoscopic resection of low rectal cancer poses significant technical difficulties for the surgeon. There is a lack of published follow-up data in relation to the surgical, oncological and survival outcomes in these patients. AIM: The aim of this study is to evaluate the surgical, oncological and survival outcomes in all patients undergoing laparoscopic resection for low rectal cancer. METHODS: Consecutive patients undergoing laparoscopic resection for low rectal cancers were included in the study. Clinical, pathological and follow-up data were recorded over a 4-year period. The mean follow-up was 25 months RESULTS: A total of 53 patients were included in the study, 30 of whom were males. The mean age was 64.14 years (range, 34-86 years). The mean hospital stay was 8.2 days (range, 4-42 days). Fifty were completed laparoscopically and three were converted to an open procedure. Thirty-eight were anterior resections and 15 were abdominoperineal resections. Twenty-four patients received neoadjuvant chemoradiotherapy. The total mesorectal excision was optimal in 51 (98%) cases. There were no anastomotic sequelae and no surgical mortality. There was no local recurrence detected. The overall survival (mean follow-up, 25 months) was 93.5%. CONCLUSION: Laparoscopic resection for low rectal cancers permits optimum oncological control. In our series, this technical approach is associated with excellent 4-year survival and clinical outcomes.

The benefit of an enhanced recovery programme following elective laparoscopic sigmoid colectomy.

BACKGROUND: Enhanced recovery programmes (ERPs) have demonstrated reduced morbidity and length of hospital stay in patients undergoing open elective colorectal resections. The application of laparoscopic techniques to colorectal surgery is associated with shorter length of stay and morbidity compared to open resections. In the setting of laparoscopic surgery, it is unclear whether there is an additive effect on length of stay and morbidity by combining these. The current study addresses the benefit of an ERP (RAPID protocol) in a cohort of matched patients undergoing laparoscopic sigmoid colon resection MATERIALS AND METHODS: Consecutive patients over a 40-month period who underwent laparoscopic sigmoid colon resection were assigned either to the RAPID protocol (group 1) or traditional post operative care (group 2) in a non-randomised manner. Analysis was on an "intention to treat" basis. Primary and secondary endpoints were identified; primary endpoints included length of hospital stay and readmission rate. Secondary endpoints included morbidity and mortality rate. RESULTS: Seventy-three consecutive patients were included. Group 1 included 37 patients. Group 2 included 36 patients. Median length of hospital stay in groups 1 and 2 was 5 and 8 days, respectively (p = 0.01). Readmission rate in groups 1 and 2 was 8.1% and 8.3%, respectively (p = 0.98). Morbidity rate in groups 1 and 2 was 30% and 22%, respectively (p = 0.61); there was one mortality in each group. CONCLUSION: The application of the ERP (RAPID) to patients undergoing laparoscopic sigmoid colon resection results in a significant improvement in length of hospital stay, with comparable morbidity and readmission rates.

Inflammatory myofibroblastic tumor with ALK/TPM3 fusion presenting as ileocolic intussusception: an unusual presentation of an unusual neoplasm.

Inflammatory myofibroblastic tumor is a rare spindle cell lesion of indeterminate malignant potential occurring in both pulmonary and extrapulmonary tissues. This report describes an unusual presentation of an unusual tumor at an unusual location: an intramural ileal case of inflammatory myofibroblastic tumor presenting with intussusception in a 29-year-old woman. We characterize this tumor through microscopic and ultrastructural analysis, extensive immunohistochemical analysis, ploidy analysis, and Epstein-Barr virus in situ hybridization, and we report the finding of an ALK/TPM3 fusion using fluorescence in situ hybridization.