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.

A systematic review and meta-analysis assessing the use of tranexamic acid (TXA) in acute gastrointestinal bleeding.

INTRODUCTION: Gastrointestinal bleeding results in significant morbidity, cost and mortality. TXA, an antifibrinolytic agent, has been proposed to reduce mortality; however, many studies report conflicting results. METHODS: The aim of the study was to perform the first systematic review and meta-analysis of RCTs to evaluate the efficacy TXA for both upper and lower gastrointestinal bleeding. This was performed per PRISMA guidelines. PubMed, EMBASE, Cochrane and Scopus databases were searched for RCTs. Dichotomous variables were pooled as risk ratios (RR) with 95% confidence intervals (CI) using the MH method with random effects modelling. RESULTS: Fourteen RCTs were identified with 14,338 patients and mean age of 58.4 years. 34.9% (n = 5008) were female and 65.1% (n = 9330) male. There was no significant difference in mortality between TXA and placebo (RR 0.86 95% CI (0.74 to 1.00), P: 0.05). The secondary outcomes, similarly, did not yield significant results. These included rebleeding, need for surgical intervention (RR: 0.75 95% CI (0.53, 1.07)), endoscopic intervention (RR: 0.92 95% CI (0.70, 1.22)), transfusion requirement (RR: 1.01 95% CI (0.94, 10.7)) and length of stay (RR: 0.03 95% CI (- 0.03, 0.08)). There was no increased risk of VTE, RR: 1.29 95% CI (0.53, 3.16). One trial (n = 12,009) reported an increased risk of seizure in the TXA group, RR: 1.73 95% CI (1.03-2.93). CONCLUSION: TXA does not reduce mortality in patients with acute upper or lower gastrointestinal bleeding and may confer an increased risk of seizures. The authors do not recommend the use of TXA in acute gastrointestinal bleeding.

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.

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.

Failure to take-up public healthcare entitlements: Evidence from the Medical Card system in Ireland.

While population health and welfare can be improved through the provision of non-cash benefits, such as free healthcare, many welfare improving schemes have low rates of take up amongst those eligible for such a benefit. One interesting example of this is the Medical Card scheme in Ireland. Medical Cards are a non-cash benefit that provide free primary, community, and hospital care, as well as heavily subsidised prescriptions drugs, for those below specific income means-test threshold. However, despite the significant benefits afforded by a Medical Card, many people forego entitlement. While this has been of concern to policymakers, the prevalence of, and reason for, non-take up, have to date not been examined in-depth. Using detailed household demographic, healthcare, income and expenditure data, this paper estimates the Medical Card take-up rate, examines the reasons for non-take, and estimates the additional healthcare cost burden to individuals due to non-take-up. The paper estimates that 31% of eligible individuals do not take up a Medical Card. Private health insurance coverage, receipt of social welfare, employment status and health status are all strongly correlated with take up. Results suggest that of a lack of information about eligibility status and social stigma are key factors driving non take up. The paper estimates that families who forego their entitled Medical Card typically spend an additional €202 annually on healthcare. Furthermore, as a consequence of higher purchase rates of, perhaps unnecessary, private health insurance, families not taking up their entitlement spend an additional €489 per annum on PHI premia. Welfare losses are likely to be even higher if forgoing medical care due to cost results in future negative health outcomes.

Biofilm-sealed perforation of the gastric body: a rare sequela of gastric band erosion.

Laparoscopic Adjustable Gastric Banding is one of the cardinal bariatric interventions and due to its early safety profile, became the mainstay. Major long-term complications of gastric banding include pouch-herniation-dilation and gastric erosion. A 59-year-old female presented to the emergency department with a 2-week history of progressive central abdominal pain and distention on a background history of a laparoscopic adjustable band insertion 11 years previously. Subsequent computed tomography demonstrated an intragastric band erosion. An exploratory laparotomy demonstrated a gastric band eroded through the stomach sealed by a biofilm. Secondary findings included small bowel ischemia and portal vein thrombosis. The gastric band was extracted, and the stomach was repaired. The ischemic small bowel was resected with primary anastomosis. The patient recovered uneventfully. Gastric band erosion should be considered in all patients presenting with abdominal pain and previous weight loss surgery. Prompt recognition may avoid fatal consequences.

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.

National early warning score (NEWS) - evaluation in surgery.

PURPOSE: The purpose of this paper is to evaluate staff opinion on the impact of the National Early Warning Score (NEWS) system on surgical wards. In 2012, the NEWS system was introduced to Irish hospitals on a phased basis as part of a national clinical programme in acute care. DESIGN/METHODOLOGY/APPROACH: A modified established questionnaire was given to surgical nursing staff, surgical registrars, surgical senior house officers and surgical interns for completion six months following the introduction of the NEWS system into an Irish university hospital. FINDINGS: Amongst the registrars, 89 per cent were unsure if the NEWS system would improve patient care. Less than half of staff felt consultants and surgical registrars supported the NEWS system. Staff felt the NEWS did not correlate well clinically with patients within the first 24 hours (Day zero) post-operatively. Furthermore, 78-85 per cent of nurses and registrars felt a rapid response team should be part of the escalation protocol. RESEARCH LIMITATIONS/IMPLICATIONS: Senior medical staff were not convinced that the NEWS system may improve patient care. Appropriate audit proving a beneficial impact of the NEWS system on patient outcome may be essential in gaining support from senior doctors. Deficiencies with the system were also observed including the absence of a rapid response team as part of the escalation protocol and a lack of concordance of the NEWS in patients Day zero post-operatively. These issues should be addressed moving forward. ORIGINALITY/VALUE: Appropriate audit of the impact of the NEWS system on patient outcome may be pertinent to obtain the support from senior doctors. Deficiencies with the system were also observed including the absence of a rapid response team as part of the escalation protocol and a lack of concordance of the NEWS in patients Day zero post-operatively. These issues should be addressed moving forward.

Early post-operative removal of urethral catheter in patients undergoing colorectal surgery with epidural analgesia ­ a prospective pilot clinical study.

BACKGROUND: Urethral catheter (UC) removal is often delayed following colorectal resection due to the perceived increased risk of post-operative urinary retention (POUR) in patients with post-operative epidural analgesia (POEA). We aimed to determine if UC removal at 48 h, irrespective of ongoing POEA use, altered the risk of POUR and other morbidities associated with urethral catheterisation and immobility. METHODS: We performed a prospective randomised controlled pilot clinical study. Eligible patients were randomised to an experimental arm, SG1 (UC removal 48 h post-operatively), or a control arm, SG2 (UC removed following cessation of POEA). Rates of POUR, urinary tract infection (UTI), pulmonary complications and surgical site infection (SSI) were recorded. Forty-four patients were recruited (SG1: n = 22; SG2: n = 22). RESULTS: No females developed POUR, while it occurred in three males (20%) in SG1 and 2 males (22.2%) in SG2. All patients who developed POUR had undergone rectal resection. Males in SG1 were not at significantly increased risk of POUR compared to those in SG2 (R.R 0.875, p = 1). No patient developed UTI post-operatively. The rate of pulmonary complications (SG1: n = 2; SG2: n = 3, p = 0.229) and SSI (SG1: n = 5; SG2: n = 2, p = 0.146) were similar between both study arms. DISCUSSION: Males undergoing rectal surgery appear to be at increased risk of developing POUR in the presence of epidural analgesia, independent of the timing of UC removal. CONCLUSIONS: All female patients undergoing colorectal resection and male patients undergoing colonic resection may have their urethral catheter removed at 48 h irrespective of use of POEA. CLINICAL TRIALS REGISTRATION NUMBER: NCT01508767 (http://www.clinicaltrials.gov).

Awareness and uptake of family screening in patients diagnosed with colorectal cancer at a young age.

Background. One-fifth of people who develop colorectal cancer (CRC) have a first-degree relative (FDR) also affected. There is a large disparity in guidelines for screening of relatives of patients with CRC. Herein we address awareness and uptake of family screening amongst patients diagnosed with CRC under age 60 and compare guidelines for screening. Study Design. Patients under age 60 who received surgical management for CRC between June 2009 and May 2012 were identified using pathology records and theatre logbooks. A telephone questionnaire was carried out to investigate family history and screening uptake among FDRs. Results. Of 317 patients surgically managed for CRC over the study period, 65 were under age 60 at diagnosis (8 deceased). The mean age was 51 (30-59). 66% had node positive disease. 25% had a family history of colorectal cancer in a FDR. While American and Canadian guidelines identified 100% of these patients as requiring screening, British guidelines advocated screening for only 40%. Of 324 FDRs, only 40.9% had been screened as a result of patient's diagnosis. Conclusions. Uptake of screening in FDRs of young patients with CRC is low. Increased education and uniformity of guidelines may improve screening uptake in this high-risk population.

Modulation of gut barrier function in patients with obstructive jaundice using probiotic LP299v.

OBJECTIVES: This study aimed to determine the effect of LP229v on intestinal permeability and tumour necrosis factor (TNF) p55 receptor concentrations in patients with obstructive jaundice undergoing biliary drainage. PATIENTS AND METHODS: Patients undergoing biliary drainage were recruited and randomized into three groups to receive Lactobacillus plantarum 299v (LP299v), inactivated LP299v (placebo) or water. These were administered daily at noon until 7 days after biliary drainage. Intestinal permeability was measured using the lactulose/mannitol (L/M) dual sugar absorption test on admission, the day before biliary drainage and on days 1 and 7 after biliary drainage. Blood and urine were collected to determine the L/M ratio and the TNF p55 receptor levels at each time point. RESULTS: A total of 25 patients were recruited; 12 had choledocholithiasis and nine had a periampullary tumour. Open surgical biliary drainage was performed in nine patients, endoscopic retrograde cholangiopancreatography in 12 and percutaneous transhepatic cholangiography in two. Five patients received LP299v, five received placebo and seven, water. The median L/M ratio was 0.035 (0.018-0.065) at baseline. No difference existed between the groups on admission, before drainage and on day 7 after drainage (P=0.59, 0.175 and 0.61, respectively). The L/M ratio was lower in the LP299v group on day 1 after drainage [0.01 (0.01) vs. 0.18 (0.03-0.3) and 0.11 (0.07-0.14); P=0.37]. Although the TNF p55 receptor levels were lower on day 1 after drainage in the LP299v group (15.3 vs. 30.9 vs. 82.7 ng/ml; P=0.43), the concentration at the four time points was similar (P=0.24, 0.96, 0.43 and 0.68). CONCLUSION: Pretreatment with probiotic LP299v improves intestinal permeability after biliary drainage and attenuates the inflammatory response. However, a larger multicentre trial is required to determine the effect on clinical outcome.

MicroRNA signature analysis in colorectal cancer: identification of expression profiles in stage II tumors associated with aggressive disease.

PURPOSE: Colorectal cancer (CRC) is a clinically diverse disease whose molecular etiology remains poorly understood. The purpose of this study was to identify miRNA expression patterns predictive of CRC tumor status and to investigate associations between microRNA (miRNA) expression and clinicopathological parameters. METHODS: Expression profiling of 380 miRNAs was performed on 20 paired stage II tumor and normal tissues. Artificial neural network (ANN) analysis was applied to identify miRNAs predictive of tumor status. The validation of specific miRNAs was performed on 102 tissue specimens of varying stages. RESULTS: Thirty-three miRNAs were identified as differentially expressed in tumor versus normal tissues. ANN analysis identified three miRNAs (miR-139-5p, miR-31, and miR-17-92 cluster) predictive of tumor status in stage II disease. Elevated expression of miR-31 (p = 0.004) and miR-139-5p (p < 0.001) and reduced expression of miR-143 (p = 0.016) were associated with aggressive mucinous phenotype. Increased expression of miR-10b was also associated with mucinous tumors (p = 0.004). Furthermore, progressively increasing levels of miR-10b expression were observed from T1 to T4 lesions and from stage I to IV disease. CONCLUSION: Association of specific miRNAs with clinicopathological features indicates their biological relevance and highlights the power of ANN to reliably predict clinically relevant miRNA biomarkers, which it is hoped will better stratify patients to guide adjuvant therapy.

Impact of pulmonary system limitations on locomotor muscle fatigue in patients with COPD.

We examined the effects of respiratory muscle work [inspiratory (W(r-insp)); expiratory (W(r-exp))] and arterial oxygenation (Sp(O(2))) on exercise-induced locomotor muscle fatigue in patients with chronic obstructive pulmonary disease (COPD). Eight patients (FEV, 48 +/- 4%) performed constant-load cycling to exhaustion (Ctrl; 9.8 +/- 1.2 min). In subsequent trials, the identical exercise was repeated with 1) proportional assist ventilation + heliox (PAV); 2) heliox (He:21% O(2)); 3) 60% O(2) inspirate (hyperoxia); or 4) hyperoxic heliox mixture (He:40% O(2)). Five age-matched healthy control subjects performed Ctrl exercise at the same relative workload but for 14.7 min ( approximately best COPD performance). Exercise-induced quadriceps fatigue was assessed via changes in quadriceps twitch force (Q(tw,pot)) from before to 10 min after exercise in response to supramaximal femoral nerve stimulation. During Ctrl, absolute workload (124 +/- 6 vs. 62 +/- 7 W), W(r-insp) (207 +/- 18 vs. 301 +/- 37 cmH(2)O x s x min(-1)), W(r-exp) (172 +/- 15 vs. 635 +/- 58 cmH(2)O x s x min(-1)), and Sp(O(2)) (96 +/- 1% vs. 87 +/- 3%) differed between control subjects and patients. Various interventions altered W(r-insp), W(r-exp), and Sp(O(2)) from Ctrl (PAV: -55 +/- 5%, -21 +/- 7%, +6 +/- 2%; He:21% O(2): -16 +/- 2%, -25 +/- 5%, +4 +/- 1%; hyperoxia: -11 +/- 2%, -17 +/- 4%, +16 +/- 4%; He:40% O(2): -22 +/- 2%, -27 +/- 6%, +15 +/- 4%). Ten minutes after Ctrl exercise, Q(tw,pot) was reduced by 25 +/- 2% (P < 0.01) in all COPD and 2 +/- 1% (P = 0.07) in healthy control subjects. In COPD, DeltaQ(tw,pot) was attenuated by one-third after each interventional trial; however, most of the exercise-induced reductions in Q(tw,pot) remained. Our findings suggest that the high susceptibility to locomotor muscle fatigue in patients with COPD is in part attributable to insufficient O(2) transport as a consequence of exaggerated arterial hypoxemia and/or excessive respiratory muscle work but also support a critical role for the well-known altered intrinsic muscle characteristics in these patients.

Cardiac compromise due to a pancreatic mediastinal pseudocyst.

Cardiac complications from a pancreatic mediastinal pseudocyst are rare. Pericardial effusions associated with pancreatitis have been reported only very occasionally. To the best of our knowledge, the direct extension of a pancreatic pseudocyst into the pericardial sac causing tamponade has not been described before. We present a case in which a pancreatic pseudocyst masquerading as a pericardial effusion dissected into the mediastinum, eroding into the pericardial sac and causing a life-threatening pericardial tamponade. A pericardial catheter was placed producing rapid symptomatic relief. Surgery was avoided by the use of octreotide as an adjuvant to ultrasound guided catheter drainage of the pseudocyst and it resolved completely within 4 weeks of admission to hospital. The importance of rapid and accurate diagnosis of this life-threatening complication is reiterated and the management of pancreatic mediastinal pseudocyst is discussed.