Influence of neoadjuvant treatment strategy on perioperative outcomes in locally advanced rectal cancer.

AIM: Neoadjuvant chemoradiotherapy (nCRT) in locally advanced rectal cancer facilitates tumour downstaging and complete pathological response (pCR). The goal of neoadjuvant systemic chemotherapy (total neoadjuvant chemotherapy, TNT) is to further improve local and systemic control. While some patients forgo surgery, total mesorectal excision (TME) remains the standard of care. While TNT appears to be noninferior to nCRT with respect to short-term oncological outcomes few data exist on perioperative outcomes. Perioperative morbidity including anastomotic leaks is associated with a negative effect on oncological outcomes, probably due to a delay in proceeding to adjuvant therapy. Thus, we aimed to compare conversion rates, rates of sphincter-preserving surgery and anastomosis formation rates in patients undergoing rectal resection after either TNT or standard nCRT. METHODS: An institutional colorectal oncology database was searched from January 2018 to July 2023. Inclusion criteria comprised patients with histologically confirmed rectal cancer who had undergone neoadjuvant therapy and TME. Exclusion criteria comprised patients with a noncolorectal primary, those operated on emergently or who had local excision only. Outcomes evaluated included rates of conversion to open, sphincter-preserving surgery, anastomosis formation and anastomotic leak. RESULTS: A total of 119 patients were eligible for inclusion (60 with standard nCRT, 59 with TNT). There were no differences in rates of sphincter preservation or primary anastomosis formation between the groups. However, a significant increase in conversion to open (p = 0.03) and anastomotic leak (p = 0.03) was observed in the TNT cohort. CONCLUSION: In this series TNT appears to be associated with higher rates of conversion to open surgery and higher anastomotic leak rates. While larger studies will be required to confirm these findings, these factors should be considered alongside oncological benefits when selecting treatment strategies.

Evaluating the oncological safety of neoadjuvant chemotherapy in locally advanced colon carcinoma: a systematic review and meta-analysis of randomised clinical trials and propensity-matched studies.

PURPOSE: Use of neoadjuvant chemotherapy (NAC) for locally advanced colon cancer (LACC) remains controversial. An integrated analysis of data from high-quality studies may inform the long-term safety of NAC for this cohort. Our aim was to perform a systematic review and meta-analysis of randomised clinical trials (RCTs) and propensity-matched studies to assess the oncological safety of NAC in patients with LACC. METHODS: A systematic review was performed as per preferred reporting items for systematic reviews and meta-analyses (PRISMA) guidelines. Survival was expressed as hazard ratios using time-to-effect generic inverse variance methodology, while surgical outcomes were expressed as odds ratios (ORs) using the Mantel-Haenszel method. Data analysis was performed using Review Manager version 5.4. RESULTS: Eight studies (4 RCTs and 4 retrospective studies) including 31,047 patients with LACC were included. Mean age was 61.0 years (range: 19-93 years) and mean follow-up was 47.6 months (range: 2-133 months). Of those receiving NAC, 4.6% achieved a pathological complete response and 90.6% achieved R0 resection (versus 85.9%, P < 0.001). At 3 years, patients receiving NAC had improved disease-free survival (DFS) (OR: 1.28, 95% confidence interval (CI): 1.02-1.60, P = 0.030) and overall survival (OS) (OR: 1.76, 95% CI: 1.10-2.81, P = 0.020). When using time-to-effect modelling, a non-significant difference was observed for DFS (HR: 0.79, 95% CI: 0.57-1.09, P = 0.150) while a significant difference in favour of NAC was observed for OS (HR: 0.75, 95% CI: 0.58-0.98, P = 0.030). CONCLUSION: This study highlights the oncological safety of NAC for patients being treated with curative intent for LACC using RCT and propensity-matched studies only. These results refute current management guidelines which do not advocate for NAC to improve surgical and oncological outcomes in patients with LACC. TRIAL REGISTRATION: International Prospective Register of Systematic Review (PROSPERO) registration: CRD4202341723.

Comparison of triamcinolone and methylprednisolone efficacy and steroid flare reaction rates after shoulder corticosteroid injection: a prospective interrupted time series study.

BACKGROUND: A corticosteroid flare reaction is a well-described phenomenon that causes significant pain and dysfunction. The paucity of literature impedes decision making regarding which corticosteroid to use for shoulder injection. The purpose of this study was to compare methylprednisolone acetate (MPA) and triamcinolone acetonide (TA) injections in the glenohumeral joint and/or subacromial space in terms of efficacy and the incidence of steroid flare reactions. METHODS: In this prospective, interrupted time series, parallel study, patients received injections in the glenohumeral joint and/or subacromial space. MPA and TA were used during 2 discrete 3-month periods. The injections consisted of 2 mL of lidocaine, 2 mL of bupivacaine, and 80 mg of either MPA or TA. Visual analog scale (VAS) pain scores were recorded immediately before injection; 1-7 days after injection; and 3, 6, and 12 months after injection. The primary outcome was the incidence of a steroid flare reaction, defined as a post-injection increase in the VAS score by ≥2 points. The secondary outcome was injection failure, defined as a post-injection VAS score greater than the baseline score or the need for another intervention. We used linear mixed models with a patient-level random intercept to identify the mean VAS score change for TA injections in the first week after injection. RESULTS: MPA or TA shoulder injections were administered in 421 patients; of these patients, 15 received bilateral-joint injections whereas 406 received a single-joint injection, for a total of 436 injections (209 MPA and 227 TA injections). Pain scores in the first week after injection were available for 193 MPA and 199 TA injections. Significantly more patients in the MPA cohort reported flare reactions compared with the TA cohort (22.8% vs. 4.0%, P < .001) during the first week after injection. In the first week after injection, the mean VAS score of patients receiving TA injections was 1.05 (95% confidence interval, 0.47-1.63) lower than that of patients receiving MPA injections when adjusted for age, sex, race, pain type, surgeon type, and injection site. At 3 months, surveys for 169 MPA and 172 TA injections were completed, with no significant difference in the rate of injection failure for MPA vs. TA (42.6% vs. 36.1%, P = .224). Treatment failure rates were significantly higher for MPA than for TA at 6 months (78.44% vs. 62.5%, P < .001) but not at 12 months (81.18% vs. 81.42%, P = .531.) CONCLUSION: TA injections resulted in a >5-fold reduction in steroid flare reactions, with statistically superior 6-month efficacy rates, compared with MPA injections. This study supports TA as a more viable corticosteroid option for shoulder injection.

Impact of the 12-gene recurrence score in influencing adjuvant chemotherapy prescription in mismatch repair proficient stage II/III colonic carcinoma-a systematic review and meta-analysis.

INTRODUCTION: The 12-gene recurrence score (RS) is a clinically validated assay which predicts recurrence risk in patients with stage II/III colon cancer. Decisions regarding adjuvant chemotherapy may be guided using this assay or based on the judgement of tumour board. AIMS: To assess the concordance between the RS and MDT decisions regarding adjuvant chemotherapy in colon cancer. METHODS: A systematic review was performed in accordance with PRISMA guidelines. Meta-analyses were performed using the Mantel-Haenszel method using the Review Manager version 5.4 software. RESULTS: Four studies including 855 patients with a mean age of 68 years (range: 25-90 years) met inclusion criteria. Overall, 79.2% had stage II disease (677/855) and 20.8% had stage III disease (178/855). For the entire cohort, concordant results between the 12-gene assay and MDT were more likely than discordant (odds ratio (OR): 0.38, 95% confidence interval (CI): 0.25-0.56, P < 0.001). Patients were more likely to have chemotherapy omitted than escalated when using the RS (OR: 9.76, 95% CI: 6.72-14.18, P < 0.001). For those with stage II disease, concordant results between the 12-gene assay and MDT were more likely than discordant (OR: 0.30, 95% CI: 0.17-0.53, P < 0.001). In stage II disease, patients were more likely to have chemotherapy omitted than escalated when using the RS (OR: 7.39, 95% CI: 4.85-11.26, P < 0.001). CONCLUSIONS: The use of the 12-gene signature refutes the decision of tumour board in 25% of cases, with 75% of discordant decisions resulting in omission of adjuvant chemotherapy. Therefore, it is possible that a proportion of such patients are being overtreated when relying on tumour board decisions alone.

Efficacy of Postoperative Oral Antibiotics in Foot and Ankle Surgery.

BACKGROUND: Preoperative oral antibiotic use in patients undergoing foot and ankle surgery is standard practice, but no consensus has been reached regarding the efficacy of postoperative oral antibiotics. The purpose of this study was to determine whether postoperative oral antibiotics reduce the rate of surgical site infections (SSIs) in patients, with and without comorbidities, undergoing foot and ankle surgery. METHODS: A retrospective chart review was conducted identifying patients who underwent foot and ankle surgery by 4 fellowship-trained, foot and ankle orthopaedic surgeons between January 1, 2015, and January 1, 2019. Patients were divided into 2 groups: those who received postoperative oral antibiotics (group 1) and those who did not (group 2). Two surgeons routinely prescribed postoperative oral antibiotics, and 2 did not. Demographics, comorbidities, and procedure complexity based on surgical site and Current Procedural Terminology code were recorded from the charts. The primary outcome was postoperative infection (superficial or deep) within 6 months after surgery. Patients with antibiotic use prior to surgery, preoperative infection, or lack of follow-up >6 weeks were excluded. Multivariate logistic regression modeling was used to analyze differences in infection rate and severity. RESULTS: Chart review identified 3631 patients, 1227 of whom did not receive postoperative oral antibiotics whereas 2394 patients did. Routine postoperative oral antibiotic use did not significantly affect postoperative infection rates or severity. However, all covariates studied (diabetes, hypertension, obesity, tobacco use, alcohol use, rheumatoid conditions, and age) influenced postoperative infection rates and severity. CONCLUSION: The results of this study indicate that postoperative oral antibiotics are not associated with differences in infection rates or severity. We do not recommend routine use in foot and ankle surgery.

Opioid-sparing pain management protocol after shoulder arthroplasty results in less opioid consumption and higher satisfaction: a prospective, randomized controlled trial.

BACKGROUND: The opioid epidemic has become a central focus in health care. In an effort to reduce opioid use, orthopedic surgeons use multimodal strategies to control postoperative pain. However, no clear consensus exists on ideal pain management strategies after shoulder arthroplasty, and most protocols are opioid-driven. This study sought to determine if patients undergoing shoulder arthroplasty using a postoperative opioid-sparing pain-control regimen would have equivalent pain scores and satisfaction as patients using a traditional opioid-based regimen. METHODS: Patients undergoing primary anatomic or reverse total shoulder arthroplasty were prospectively enrolled and randomized into an opioid-sparing (OS) or a traditional opioid-based (OB) postoperative pain protocol. Both groups received opioid education, periarticular injection with liposomal bupivacaine, and preoperative and postoperative multimodal management (acetaminophen, celecoxib, and gabapentin). The OB group was discharged with 40 oxycodone tablets and standard icing, whereas the OS group received ketorolac during admission, continuous cryotherapy, and discharged with 10 oxycodone tablets for rescue. Patients were queried regarding levels of pain and opioid consumption at days 1-7 and at 2, 6, and 12 weeks postoperatively. Patient satisfaction was recorded at 1, 2, 6, and 12 weeks. Range of motion (ROM), American Shoulder and Elbow Surgeons Standardized Shoulder Assessment Form (ASES), and Single Assessment Numerical Evaluation (SANE) scores were assessed preoperatively and at 12 weeks postoperatively. Complications, readmissions, and reoperations were recorded. RESULTS: In 78 patients, no difference in VAS pain scores were seen at any time between groups. The OS group consumed less oral morphine equivalents (OME) from inpatient hospitalization to 12 weeks postoperatively (P < .05). Total OME consumption was reduced by 213% for the OS vs. the OB group (112 vs. 239; P < .0001). The OS group consumed fewer opioid pills at all time points (P < .05). A 395% reduction in number of opioid pills consumed in the first 12 weeks postoperatively was seen in the OS vs. the OB group (4.3 vs. 17.0; P < .0001). Significantly more patients in the OS group discontinued opioids by 2 weeks postoperatively (86.1% vs. 58.5%; P = .011), and 94.4% in the OS group discontinued opioids by 6 weeks postoperatively. The OS group was more satisfied with pain management at 1 and 6 weeks (P = .05). No difference in ROM, ASES or SANE scores, complications, readmissions, or reoperations were seen between groups. CONCLUSIONS: This study demonstrated a nearly 4-fold reduction in opioid pain pill consumption and earlier cessation of opioids with an OS pain management protocol. Patients also reported higher satisfaction with this pain management strategy.

Riding the waves: the ongoing impact of COVID-19 on a national surgical training cohort.

BACKGROUND: The World Health Organisation declared a global pandemic on the 11 March 2020 resulting in implementation of methods to contain viral spread, including curtailment of all elective and non-emergent interventions. Many institutions have experienced changes in rostering practices and redeployment of trainees to non-surgical services. Examinations, study days, courses, and conferences have been cancelled. These changes have the potential to significantly impact the education and training of surgical trainees. AIM: To investigate the impact of the COVID-19 pandemic on training, educational, and operative experiences of Irish surgical trainees. METHODS: Surgical trainees were surveyed anonymously regarding changes in working and educational practices since the declaration of the COVID-19 pandemic on 11 March 2020. The survey was circulated in May 2020 to both core and higher RCSI surgical trainees, when restrictions were at level five. Questions included previous and current access to operative sessions as well as operative cases, previous and current educational activities, access to senior-led training, and access to simulation-/practical-based training methods. A repeat survey was carried out in October 2020 when restrictions were at level two. RESULTS: Overall, primary and secondary survey response rates were 29% (n = 98/340) and 19.1% (n = 65/340), respectively. At the time of circulation of the second survey, the number of operative sessions attended and cases performed had significantly improved to numbers experienced pre-pandemic (p < 0.0001). Exposure to formal teaching and education sessions returned to pre-COVID levels (p < 0.0001). Initially, 23% of trainees had an examination cancelled; 53% of these trainees have subsequently sat these examinations. Of note 27.7% had courses cancelled, and 97% of these had not been rescheduled. CONCLUSION: Surgical training and education have been significantly impacted in light of COVID-19. This is likely to continue to fluctuate in line with subsequent waves. Significant efforts have to be made to enable trainees to meet educational and operative targets.

Reliability Testing of the Mayo Elbow Performance Score in Post-operative Patients.

This study aimed to determine intra-observer and inter-observer reliability of the Mayo Elbow Performance Score (MEPS). Patients undergoing elbow surgery completed a MEPS questionnaire initially and another 2-3 weeks later. During the second interview, patients completed the Oxford Elbow Score (OES) for comparison. Intraclass correlation coefficients (ICC) and Pearson correlation coefficients (PCC) > 0.80 indicated substantial agreement. In 42 patients who had elbow surgery, the average MEPS score initially was 78 (range, 5-100, SD 22.4) and 77 (range, 5-100, SD 21.5) at second interview. The average normalized OES score was 79 (range, 17-100, SD 23.6). The ICC for MEPS scores at the two time points was 0.90, and the PCC between the MEPS and OES scores was 0.87, indicating substantial agreement. The MEPS has strong intra-observer reliability at different time points and strong inter-observer reliability when compared with the OES, validating the MEPS as an outcome measure of elbow surgery. (Journal of Surgical Orthopaedic Advances 31(4):229-232, 2022).

The use of radiomic analysis of magnetic resonance imaging in predicting distant metastases of rectal carcinoma following surgical resection: A systematic review and meta-analysis.

AIM: Estimating prognosis in rectal carcinoma (RC) is challenging, with distant recurrence (DR) occurring in up to 30% of cases. Radiomics is a novel field using diagnostic imaging to investigate the tumour heterogeneity of cancers and may have the potential to predict DR. The aim of the study was to perform a systematic review of the current literature evaluating the use of radiomics in predicting DR in patients with resected RC. METHODS: A systematic review was performed as per PRISMA guidelines to identify studies reporting radiomic analysis of magnetic resonance imaging (MRI) to predict DR in patients diagnosed with RC. Sensitivity and specificity of radiomic analyses were included for meta-analysis. RESULTS: A total of seven studies including 1497 patients (998 males) were included, seven, five and one of whom reported radiomics, respectively. The overall pooled rate of DR from all included studies was 17.1% (256/1497), with 15.6% (236/1497), 1.3% (19/1497) and 0.2% (3/1497) of patients having hepatic, pulmonary and peritoneal metastases. Meta-analysis demonstrated that radiomics correctly predicted DR with pooled sensitivities and specificities of MRI 0.76 (95% CI: 0.73, 0.78) and 0.85 (95% CI: 0.83, 0.88), respectively. CONCLUSION: This systematic review suggests the benefit of radiomic analysis of preoperative MRI in identifying patients with resected RC at an increased risk of DR. Our findings warrant validation in larger prospective studies as modalities to predict DR is a significant unmet need in RC. Radiomics may allow for tailored therapeutic strategies for high-risk groups.

Subtotal colectomy in ulcerative colitis-long term considerations for the rectal stump.

BACKGROUND: The initial operation of choice in many patients presenting as an emergency with ulcerative colitis is a subtotal colectomy with end ileostomy. A percentage of patients do not proceed to completion proctectomy with ileal pouch anal anastomosis. AIM: To review the existing literature in relation to the significant long-term complic-ations associated with the rectal stump, to provide an overview of options for the surgical management of remnant rectum and anal canal and to form a consolidated guideline on endoscopic screening recommendations in this cohort. METHODS: A systematic review was carried out in accordance with PRISMA guidelines for papers containing recommendations for endoscopy surveillance in rectal remnants in ulcerative colitis. A secondary narrative review was carried out exploring the medical and surgical management options for the retained rectum. RESULTS: For rectal stump surveillance guidelines, 20% recommended an interval of 6 mo to a year, 50% recommended yearly surveillance 10% recommended 2 yearly surveillance and the remaining 30% recommended risk stratification of patients and different screening intervals based on this. All studies agreed surveillance should be carried out via endoscopy and biopsy. Increased vigilance is needed in endoscopy in these patients. Literature review revealed a number of options for surgical management of the remnant rectum. CONCLUSION: The retained rectal stump needs to be surveyed endoscopically according to risk stratification. Great care must be taken to avoid rectal perforation and pelvic sepsis at time of endoscopy. If completion proctectomy is indicated the authors favour removal of the anal canal using an intersphincteric dissection technique.

Evaluation of a Novel Ostomy Barrier Ring with Assisted Flow for Individuals with an Ileostomy.

OBJECTIVE: To determine the performance and user experience of a novel ostomy barrier ring over a 4-week period. METHODS: This single-arm investigation conducted across three clinical sites included 25 adult participants with an ileostomy for 3 months or longer. The participants used their standard ostomy pouching appliance along with a novel barrier ring for a period of 4 weeks. Skin condition was assessed using the Ostomy Skin Tool. Change in skin condition over the study period was recorded for each participant. The participants' experience in using the novel barrier ring was measured using a five-point Likert-type scale. RESULTS: Twenty of the 25 participants (80%) completed the trial. Of those participants, the median Ostomy Skin Tool score at both the beginning (range, 0-8) and end was 0 (range, 0-6). In terms of skin condition, 7 participants experienced an improvement in skin condition, 11 experienced no change, and 2 got worse. A median score of 5 out of 5 was recorded for all questions relating to user experience. CONCLUSIONS: Although not statistically significant, there was a clear trend toward improvements in peristomal skin condition using the novel barrier ring, even for participants who were already using a barrier ring. User feedback was positive with respect to comfort, device handling, and the perception of the device's ability to protect the skin. Further, most participants who already used a barrier ring indicated that the novel barrier ring would result in a longer wear time.

The road to consultancy: an epidemiological study.

BACKGROUND: Modern medical and surgical training pathways have developed globally in response to changing expectations and requirements for trainees. AIMS: To determine the demographic, educational, and training characteristics of consultants in a model 4 teaching hospital, and to evaluate the requirements met by consultant physicians and surgeons prior to their appointment to consultancy. METHOD: A single-centre study conducted by prospectively distributing written questionnaires. Data was collected and analysed using Microsoft Excel and SPSS. RESULTS: This questionnaire was offered to 166 consultants, 110 of whom responded (66.0%). The vast majority were Irish (91.8%) and 70.9% male. The mean age to appointment was 35.7 ± 2.6 years. Radiology was the specialty with the youngest mean age at appointment: 34.4 ± 2.6 years, while surgery had the oldest: 36.7 ± 2.7 (P = 0.035). Overall, 80.9% trained via Higher Specialist Training (HST) schemes (89/110) and 68.2% completed a higher degree (75/110). Geriatric medicine and dermatology had the highest rate of completed higher degrees (100.0%, 3/3 and 3/3 respectively), followed by surgeons (92.3%; 24/26) and cardiologists (71.4%; 5/7). The overall duration of HST varied greatly; the mean surgical, medical and anaesthesiology durations were 6.7 ± 1.8 years, 6.6 ± 1.7 years, and 5.3 ± 2.0 years. A total of 75.4% of consultants completed fellowship (83/110). CONCLUSION: This study highlights variations in postgraduate Irish medical training pathways and discrepancies in training requirements expected in each specialty. The establishment of a modern guideline for young trainees working towards consultancy may be imperative in ensuring trainees have insight into training requirements expected in their specialty.

When the bowel meets the bladder: Optimal management of colorectal pathology with urological involvement.

Fistulae between the gastrointestinal and urinary systems are rare but becoming increasingly more common in current surgical practice. They are a heterogeneous group of pathological entities that are uncommon complications of both benign and malignant processes. As the incidence of complicated diverticular disease and colorectal malignancy increases, so too does the extent of fistulous connections between the gastrointestinal and urinary systems. These complex problems will be more common as a factor of an aging population with increased life expectancy. Diverticular disease is the most commonly encountered aetiology, accounting for up to 80% of cases, followed by colorectal malignancy in up to 20%. A high index of suspicion is required in order to make the diagnosis, with ever improving imaging techniques playing an important role in the diagnostic algorithm. Management strategies vary, with most surgeons now advocating for a single-stage approach to enterovesical fistulae, particularly in the elective setting. Concomitant bladder management techniques are also disputed. Traditionally, open techniques were the standard; however, increased experience and advances in surgical technology have contributed to refined and improved laparoscopic management. Unfortunately, due to the relative rarity of these entities, no randomised studies have been performed to ascertain the most appropriate management strategy. Rectourinary fistulae have dramatically increased in incidence with advances in the non-operative management of prostate cancer. With radiotherapy being a major contributing factor in the development of these complex fistulae, optimum surgical approach and exposure has changed accordingly to optimise their management. Conservative management in the form of diversion therapy is effective in temporising the situation and allowing for the diversion of faecal contents if there is associated soiling, macerated tissues or associated co-morbidities. One may plan for definitive surgical intervention at a later stage. Less contaminated cases with no fibrosis may proceed directly to definitive surgery if the appropriate expertise is available. An abdominal approach with direct repair and omentum interposition between the repaired tissues has been well described. In low lying fistulae, a transperineal approach with the patient in a prone-jack knife position provides optimum exposure and allows for the use of interposition muscle grafts. According to recent literature, it offers a high success rate in complex cases.

Neoadjuvant radiotherapy for rectal cancer management.

Thirty per cent of all colorectal tumours develop in the rectum. The location of the rectum within the bony pelvis and its proximity to vital structures presents significant therapeutic challenges when considering neoadjuvant options and surgical interventions. Most patients with early rectal cancer can be adequately managed by surgery alone. However, a significant proportion of patients with rectal cancer present with locally advanced disease and will potentially benefit from down staging prior to surgery. Neoadjuvant therapy involves a variety of options including radiotherapy, chemotherapy used alone or in combination. Neoadjuvant radiotherapy in rectal cancer has been shown to be effective in reducing tumour burden in advance of curative surgery. The gold standard surgical rectal cancer management aims to achieve surgical removal of the tumour and all draining lymph nodes, within an intact mesorectal package, in order to minimise local recurrence. It is critically important that all rectal cancer cases are discussed at a multidisciplinary meeting represented by all relevant specialties. Pre-operative staging including CT thorax, abdomen, pelvis to assess for distal disease and magnetic resonance imaging to assess local involvement is essential. Staging radiology and MDT discussion are integral in identifying patients who require neoadjuvant radiotherapy. While Neoadjuvant radiotherapy is potentially beneficial it may also result in morbidity and thus should be reserved for those patients who are at a high risk of local failure, which includes patients with nodal involvement, extramural venous invasion and threatened circumferential margin. The aim of this review is to discuss the role of neoadjuvant radiotherapy in the management of rectal cancer.

Peptoid microsphere coatings: The effects of helicity, temperature, pH, and ionic strength.

Peptoids are peptidomimetic oligomers that predominantly harness similarities to peptides for biomimetic functionality. They have potential for use in biomedical applications and biosensors due to resistance to proteolytic degradation and low immunogenicity. The incorporation of chiral, aromatic side chains in the peptoid sequence allows for the formation of distinct secondary structures and self-assembly into supramolecular assemblies, including microspheres. Peptoid microspheres can be coated onto substrates for potential use in biosensor technologies, tissue engineering platforms, and drug-delivery systems. In order to be useful for these applications, the peptoid coatings must be robust under physiological conditions. In this study, we report the effects of various conditions on the peptoid microsphere coatings, including (i) helicity, (ii) temperature, (iii) pH, and (iv) ionic strength. These studies show that microsphere size decreases with increasing peptoid helicity and the positively charged side chains are positioned on the outside of the microspheres. The peptoid microsphere coatings are robust under physiological conditions but degrade in acidic conditions (pH < 7) and at low ionic strengths (<150 µM).

Anal advancement flap versus lateral internal sphincterotomy for chronic anal fissure- a systematic review and meta-analysis.

BACKGROUND: Chronic anal fissures (CAF) are common and associated with reduced quality of life. Lateral internal sphincterotomy (LIS) is frequently carried out but carries a significant risk of anal incontinence. Anal advancement flap (AAF) has been advocated as an alternative, 'sphincter-preserving' procedure. We aimed to perform a systematic review and meta-analysis to compare the efficacy of both techniques in the treatment of CAF. METHODS: The online databases of PubMed/Medline, CINAHL, EMBASE and Cochrane Central Register of Controlled Trials were searched from inception to January 2017. All studies that investigated and reported outcomes of LIS and AAF for treatment of CAF were included. The primary outcome measure was anal incontinence while secondary outcomes included unhealed fissure and wound complication rates. Random effects models were used to calculate pooled effect size estimates. RESULTS: Four studies (2 randomized controlled trials and 2 retrospective studies) describing 300 patients (150 LIS, 150 AAF) fulfilled our inclusion criteria. There was significant clinical heterogeneity among the trials. On random effects analysis, AAF was associated with a significantly lower rate of anal incontinence compared to LIS (OR = 0.06, 95% CI = 0.01 to 0.36, p = .002). However, there were no statistically significant differences in unhealed fissure (OR = 2.21, 95% CI = 0.25 to 19.33, p = .47) or wound complication rates (OR = 1.41, 95% CI = 0.50 to 4.99 p = .51) between AAF and LIS. CONCLUSIONS: AAF is associated with less incontinence, but similar wound complications as well as a similar rate of unhealed fissures compared to LIS. However, further well-executed, multi-centre randomized trials are required to provide stronger evidence.

Oral versus topical calcium channel blockers for chronic anal fissure-a systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: Chemical sphincterotomy with pharmacological agents is recommended as first line therapy for chronic anal fissures (CAF). Calcium channel blockers (CCB) are associated with similar efficacy but fewer side effects compared to nitrates. However, the optimal formulation (oral versus topical) is unknown. We aimed to perform a systematic review and meta-analysis to compare the effectiveness of oral and topical CCB in the treatment of CAF. METHODS: PubMed and Embase online databases were searched for relevant articles. Two independent reviewers performed methodological assessment and data extraction. Random effects models were used to calculate pooled effect size estimates. A sensitivity analysis was also carried out. RESULTS: Four randomized controlled trials describing 279 patients (138 in oral, 141 in topical group) were examined. There was significant heterogeneity among studies. On random effects analysis, topical CCB were associated with a significantly lower rate of unhealed fissure (21.3% vs. 38.4%; OR = 2.65, 95% CI = 1.50 to 4.69, p = 0.0008) when compared to oral therapy. However, there were no significant differences in fissure recurrence (5.4% vs. 5.5%; OR = 1.01, 95% CI = 0.31 to 3.33, p = 0.98) or side effects (15.6% vs. 39.1%; OR = 4.54, 95% CI = 0.46 to 44.3, p = 0.19) between topical and oral CCB. On sensitivity analysis, having excluded the most heavily biased trial, topical CCB were associated with significantly fewer side effects compared to oral therapy (4.3% vs. 38.0%; OR = 13.16, 95% CI = 5.05 to 34.3, p < 0.00001). CONCLUSIONS: Topical CCB are associated with better healing and fewer side effects when compared to oral therapy but there is no difference in recurrence rates.

Completion Proctectomy for Crohn's Colitis: Lessons Learned.

Surgical management of Crohn's disease is reserved for patients refractory to medical therapy and those who develop complications alleviated by surgery. Surgical resection may be the most efficient way to restore health in patients with stricturing and or fistulizing disease of the terminal ileum / small bowel. However, decision-making in patients with Crohn's colitis is more difficult. The merits of segmental resection versus subtotal/total colectomy versus total proctocolectomy with end ileostomy are affected by a myriad of factors, including extent of colon involvement, the patient's age, and the patient's degree of desire to avoid an ileostomy. In patients undergoing a total proctocolectomy for Crohn's colitis, the anal canal should be removed. The following case highlights the potential difficulty that may arise when the anal canal is left in situ.

Screening of exosomal microRNAs from colorectal cancer cells.

BACKGROUND: Cells release extracellular membrane vesicles including microvesicles known as exosomes. Exosomes contain microRNAs (miRNAs) however the full range within colorectal cancer cell secreted exosomes is unknown. OBJECTIVE: To identify the full range of exosome encapsulated miRNAs secreted from 2 colorectal cancer cell lines and to investigate engineering of exosomes over-expressing miRNAs. METHODS: Exosomes were isolated from HCT-116 and HT-29 cell lines. RNA was extracted from exosomes and microRNA array performed. Cells were engineered to express miR-379 (HCT-116-379) or a non-targeting control (HCT-116-NTC) and functional effects were determined. Exosomes secreted by engineered cells were transferred to recipient cells and the impact examined. RESULTS: Microvesicles 40-100 nm in size secreted by cell lines were visualised and confirmed to express exosomal protein CD63. HT-29 exosomes contained 409 miRNAs, HCT-116 exosomes contained 393, and 338 were common to exosomes from both cell lines. Selected targets were validated. HCT-116-379 cells showed decreased proliferation (12-15% decrease, p < 0.001) and decreased migration (32-86% decrease, p < 0.001) compared to controls. HCT-116-379 exosomes were enriched for miR-379. Confocal microscopy visualised transfer of HCT-116-379 exosomes to recipient cells. CONCLUSIONS: Colorectal cancer cells secrete a large number of miRNAs within exosomes. miR-379 decreases cell proliferation and migration, and miR-379 enriched exosomes can be engineered.

The curative management of synchronous rectal and prostate cancer.

OBJECTIVE: Neoadjuvant "long-course" chemoradiation is considered a standard of care in locally advanced rectal cancer. In addition to prostatectomy, external beam radiotherapy and brachytherapy with or without androgen suppression (AS) are well established in prostate cancer management. A retrospective review of ten cases was completed to explore the feasibility and safety of applying these standards in patients with dual pathology. To our knowledge, this is the largest case series of synchronous rectal and prostate cancers treated with curative intent. METHODS: Eligible patients had synchronous histologically proven locally advanced rectal cancer (defined as cT3-4Nx; cTxN1-2) and non-metastatic prostate cancer (pelvic nodal disease permissible). Curative treatment was delivered to both sites simultaneously. Follow-up was as per institutional guidelines. Acute and late toxicities were reviewed, and a literature search performed. RESULTS: Pelvic external beam radiotherapy (RT) 45-50.4 Gy was delivered concurrent with 5-fluorouracil (5FU). Prostate total dose ranged from 70.0 to 79.2 Gy. No acute toxicities occurred, excluding AS-induced erectile dysfunction. Nine patients proceeded to surgery, and one was managed expectantly. Three relapsed with metastatic colorectal cancer, two with metastatic prostate cancer. Five patients have no evidence of recurrence, and four remain alive with metastatic disease. With a median follow-up of 2.2 years (range 1.2-6.3 years), two significant late toxicities occurred; G3 proctitis in a patient receiving palliative bevacizumab and a G3 anastomotic stricture precluding stoma reversal. CONCLUSION: Patients proceeding to synchronous radical treatment of both primary sites should receive 45-50.4 Gy pelvic RT with infusional 5FU. Prostate dose escalation should be given with due consideration to the potential impact of prostate cancer on patient survival, as increasing dose may result in significant late morbidity. Review of published series explores the possibility of prostate brachytherapy as an alternative method of boost delivery. Frequent use of bevacizumab in metastatic rectal cancer may compound late rectal morbidity in this cohort. ADVANCES IN KNOWLEDGE: To our knowledge, this is the largest case series of synchronous rectal and prostate cancers treated with curative intent. This article contributes to the understanding of how best to approach definitive treatment in these patients.