Contemporary perioperative outcomes after total abdominal colectomy for ulcerative colitis in a tertiary referral centre.

OBJECTIVE: Colectomy for ulcerative colitis (UC) is common despite therapeutic advances. Post-operative morbidity and mortality demonstrate an association between hospital volumes and outcomes. This single-centre retrospective study examines outcomes after emergency colectomy for UC. METHODS: Patient demographics, perioperative variables and outcomes were collected in Beaumont Hospital between 2010 and 2023. Univariant analysis was used to assess relationships between perioperative variables and morbidity and length of stay (LOS). RESULTS: A total of 115 patients underwent total abdominal colectomy with end ileostomy for UC, 8.7 (±3.8) per annum. Indications were refractory acute severe colitis (88.7%), toxic megacolon (6.1%), perforation (4.3%), or obstruction (0.9%). Over 80% of cases were performed laparoscopically. Pre-operative steroid (93%) and biologic (77.4%) use was common. Median post-operative LOS was 8 days (interquartile range 6-12). There were no 30-day mortalities, and 30-day post-operative morbidity was 38.3%. There was no association between time to colectomy ( P  = 0.85) or biologic use ( P  = 0.24) and morbidity. Increasing age was associated with prolonged LOS ( P  = 0.01). Laparoscopic approach (7 vs. 12 days P  =0.01, 36.8% vs. 45% P  = 0.66) was associated with reduced LOS and morbidity. CONCLUSION: This study highlights contemporary outcomes after emergency colectomy for UC at a specialist high-volume, tertiary referral centre, and superior outcomes after laparoscopic surgery in the biologic era.

Collating evidence to support the validation of a simulated laparotomy incision and closure-training model.

BACKGROUND: It is essential to evaluate the functionality of surgical simulation models, in order to determine whether they perform as intended. In this study, we assessed the use of a simulated laparotomy incision and closure-training model by collating validity evidence to determine its utility as well as pre and post-test interval data. METHOD: This was a quantitative study design, informed by Messick's unified validity framework. In total, 93 participants (surgical trainees â€‹= â€‹80, experts â€‹= â€‹13) participated in this study. Evaluation of content validity and the models' relationships with other variables was conducted, along with a pre and post-test confidence assessment. RESULTS: The model was deemed realistic and useful as a teaching tool, providing strong content validity evidence. In assessment of relationships with other variables, the expert group out-performed the novice group conclusively. Pre and post-test evaluation reported a statistically significant increase in confidence levels. CONCLUSION: We present strong validity evidence of a novel laparotomy incision and closure simulation-training model.

A meta-analysis of laparoscopic versus ultrasound-guided transversus abdominis plane block in laparoscopic colorectal surgery.

BACKGROUND: Enhanced recovery programmes in laparoscopic colorectal surgery (LCS) employ combined approaches to achieve postoperative analgesia. Transversus abdominis plane (TAP) block is a locoregional anaesthetic technique that may reduce postoperative pain. AIMS: To perform a systematic review and meta-analysis to compare the effectiveness of laparoscopic- versus ultrasound-guided TAP block in LCS. METHODS: Databases were searched for relevant articles from inception until March 2022. All randomised controlled trials (RCTs) that compared laparoscopic (LTB) versus ultrasound-guided (UTB) TAP blocks in LCS were included. The primary outcome was narcotic consumption at 24 h postoperatively, whilst secondary outcomes included pain scores at 24 h postoperatively, operative time, postoperative nausea and vomiting (PONV) and complication rates. Random effects models were used to calculate pooled effect size estimates. RESULTS: Three RCTs were included capturing 219 patients. Studies were clinically heterogenous. On random effects analysis, LTB was associated with significantly lower narcotic consumption (SMD - 0.30 mg, 95% CI = - 0.57 to - 0.03, p = 0.03) and pain scores (SMD - 0.29, 95% CI = - 0.56 to - 0.03, p = 0.03) at 24 h. However, there were no differences in operative time (SMD - 0.09 min, 95% CI = - 0.40 to 0.22, p = 0.56), PONV (OR = 0.97, 95% CI = 0.36 to 2.65, p = 0.96) or complication (OR = 1.30, 95% CI = 0.64 to 2.64, p = 0.47) rates. CONCLUSIONS: LTB is associated with significantly less narcotic usage and pain at 24 h postoperatively but similar PONV, operative time and complication rates, compared to UTB. However, the data were inconsistent, and our findings require further investigation. LTB obviates the need for ultrasound devices whilst also decreasing procedure logistical complexity.

Complex surgery and optimal consent: A variety of opinions exist among healthcare professionals.

BACKGROUND: Establishing healthcare professional's views on optimal consent in complex surgery could guide tailored consent policy, improving the process in challenging scenarios. To date, no studies have established if professionals of differing specialities agree on major aspects of consent in areas such as emergency surgery and cancer surgery. METHODS: An anonymous web based survey was distributed to a variety of disciplines in a tertiary referral centre. Questions regarding optimal methods and timing of consent in emergency and cancer surgery were posed. Comparative analyses of quantitative data were performed using chi-squared test. RESULTS: 57 responses were received from doctors and nurses of varying disciplines. Differences were found between doctors of separate specialities and nurses in opinion of optimal timing of consent (p = 0.02), consent validity over time (p < 0.001) and the utility of introducing more specific consent policy (p = 0.01). Almost all respondents agreed that healthcare professionals have differing ideas of what consent is. CONCLUSIONS: This study demonstrates differences in opinion regarding optimal consent for cancer and emergency surgery. Consideration should be given to developing consensus among healthcare professionals regarding what consent for complex surgery constitutes.

Optimal management of functional anorectal pain: a systematic review and network meta-analysis.

Functional anorectal is idiopathic and characterised by severe and potentially intractable anorectal pain. The current review aims to appraise available evidence for the management of functional anorectal pain and synthesise reported outcomes using network meta-analysis. PubMed, CENTRAL and Web of Science databases were searched for studies investigating treatments for functional anorectal pain. The primary outcome was clinical improvement of symptoms and the secondary outcome was pain scores reported during follow-up. A Bayesian network meta-analysis of interventions was performed. A total of 1538 patients were included from 27 studies. Intramuscular injection of triamcinolone, sacral neuromodulation (SNM) and biofeedback were most likely to be associated with improvement in symptoms [SUCRA (triamcinolone) = 0.79; SUCRA (SNM) = 0.74; SUCRA (Biofeedback) = 0.61]. Electrogalvanic stimulation (EGS), injection of botulinum toxin A and topical glyceryl trinitrate (GTN) were less likely to produce clinical improvement [SUCRA (EGS) = 0.53; SUCRA (Botox) = 0.30; SUCRA (GTN) = 0.27]. SNM and biofeedback were associated with the largest reductions in pain scores [mean difference, range (SNM) = 4.6-8.2; (Biofeedback) = 4.6-6]. As biofeedback is noninvasive and may address underlying pathophysiology, it is a reasonable first-line choice in patients with high resting pressures or defecation symptoms. In patients with normal resting pressures, SNM or EGS are additional options. Although SNM is more likely to produce a meaningful response compared to EGS, EGS is noninvasive and has less morbidity. Whilst triamcinolone injection is associated with symptomatic clinical improvement, the magnitude of pain reduction is less.

Pragmatic use of short-course radiotherapy, chemotherapy and surgery for stage IV rectal cancer with locally advanced or symptomatic primary tumours.

INTRODUCTION: We assessed management of patients with de novo metastatic rectal cancer, referred for radiotherapy to the rectum, who were candidates for short-course radiotherapy (SCRT) and chemotherapy, followed by resection of all disease. We assessed surgical outcomes, overall survival (OS) and progression-free survival (PFS). METHODS: Retrospective review of patients meeting criteria: (i) treatment with SCRT to rectum; (ii) locally advanced primary rectal cancer; and (iii) resectable distant metastases at diagnosis. Data were collected from charts, correspondence and electronic patient records. OS and PFS were calculated using the Kaplan-Meier method. RESULTS: Between 2016 and 2020, 48 patients with stage IV rectal cancer at diagnosis were treated with SCRT. Only 15 patients (31%) had resectable metastatic disease and were intended for SCRT (25 Gy/5#), then chemotherapy, followed by resection of all sites of disease and are included in our study. 12 of the 15 surgical candidates (80%) had rectal surgery as planned, and 11 of the 15 (73%) had resection of the rectal primary and all metastatic disease. One patient had a pathological complete response (pCR), and 50% of surgical patients had a Mandard TRG of 1 or 2. Median PFS and OS for the 15 surgical candidates were 12.6 and 25.2 months, respectively, with a median FU of 21.2 months. CONCLUSION: For this cohort of patients, our treatment paradigm is pragmatic and results in excellent pathological response. However, the effectiveness of this approach should be the subject of future prospective studies.

Management of colon-invading renal cell carcinoma: Operative technique and systematic review.

Invasion into adjacent organs by non-metastatic renal cell carcinoma (RCC) occurs in 1% of patients suitable for resection. Colonic invasion is rare and presents technical challenges. No prospective data exists to guide management of these patients. We present the first reported case of a colon-invading RCC managed with simultaneous open right radical nephrectomy and extended right hemicolectomy. PubMed, Scopus and EMBASE databases were searched for relevant case reports reporting management of colon-invading renal cell carcinoma. Case reports, case series and cohort studies were eligible. A chart review was performed on a patient who presented with right-sided colon-invading RCC. Four previously reported cases were identified. The current case was managed with simultaneous open radical nephrectomy and extended right hemicolectomy. The patient remains well six months postoperatively with no evidence of disease recurrence. Histopathological evaluation of the resected specimen confirmed a T4 clear cell RCC with sarcomatoid differentiation. Colon-invading RCC is rare. This is the first reported case of right-sided, colon-invading RCC treated with radical resection. The current case confirms radical resection is a feasible management strategy for similar presentations. En bloc resection of involved organs remains the only potentially curative option for locally advanced disease.

Impact of the COVID-19 pandemic on management and outcomes in acute appendicitis: Should these new practices be the norm?

BACKGROUND: In early 2020, the COVID-19 pandemic significantly altered management of surgical patients globally. International guidelines recommended that non-operative management be implemented wherever possible (e.g. in proven uncomplicated appendicitis) to reduce pressure on healthcare services and reduce risk of peri-operative viral transmission. We sought to compare our management and outcomes of appendicitis during lockdown vs a non-pandemic period. METHODS: All presentations to our department with a clinical diagnosis of acute appendicitis between 12/03/2020 and 30/06/2020 were compared to the same 110-day period in 2019. Quantity and severity of presentations, use of radiological investigations, rate of operative intervention and histopathological findings were variables collected for comparison. RESULTS: There was a reduction in appendicitis presentations (from 74 to 56 cases), and an increase in radiological imaging (from 70.27% to 89.29%) (P = 0.007) from 2019 to 2020. In 2019, 93.24% of patients had appendicectomy, compared to 71.42% in 2020(P < 0.001). This decrease was most pronounced in uncomplicated cases, whose operative rates dropped from 90.32% to 62.5% (P = 0.009). Post-operative histology confirmed appendicitis in 73.9% in 2019, compared to 97.5% in 2020 (P = 0.001). Normal appendiceal pathology was reported for 17 cases (24.64%) in 2019, compared to none in 2020 (P < 0.001) - a 0% negative appendicectomy rate (NAR). DISCUSSION: The 0% NAR in 2020 is due to a combination of increased CT imaging, a higher threshold to operate, and is impacted by increased disease severity due to delayed patient presentation. This study adds to growing literature promoting routine use of radiological imaging to confirm appendicitis diagnosis. As we enter a second lockdown, patients should be encouraged to avoid late presentations, and surgical departments should continue using radiological imaging more liberally in guiding appendicitis management.

A Randomized Clinical Trial Evaluating the Efficacy and Quality of Life of Antibiotic-only Treatment of Acute Uncomplicated Appendicitis: Results of the COMMA Trial.

OBJECTIVE: Evaluate the efficacy and quality of life associated with conservative treatment of acute uncomplicated appendicitis. SUMMARY BACKGROUND DATA: Conservative management with antibiotics only has emerged as a potential treatment option for acute uncomplicated appendicitis. However the reported failure rates are highly variable and there is a paucity of data in relation to quality of life. METHODS: Symptomatic patients with radiological evidence of acute, uncomplicated appendicitis were randomized to either intravenous antibiotics only or undergo appendectomy. RESULTS: One hundred eighty-six patients underwent randomization. In the antibiotic-only group, 23 patients (25.3%) experienced a recurrence within 1 year following randomization. There was a significantly better EQ-VAS quality of life score in the surgery group compared with the antibiotic-only group at 3 months (94.3 vs 91.0, P < 0.001) and 12 months postintervention (94.5 vs 90.4, P < 0.001). The EQ-5D-3L quality-of-life score was significantly higher in the surgery group indicating a better quality of life (0.976 vs 0.888, P < 0.001). The accumulated 12-month sickness days was 3.6 days shorter for the antibiotics only group (5.3 vs 8.9 days; P < 0.01). The mean length of stay in both groups was not significantly different (2.3 vs 2.8 days, P = 0.13). The mean total cost in the surgery group was significantly higher than antibiotics only group (€4,816 vs €3,077, P < 0.001). CONCLUSIONS: Patients with acute, uncomplicated appendicitis treated with antibiotics only experience high recurrence rates and an inferior quality of life. Surgery should remain the mainstay of treatment for this commonly encountered acute surgical condition.

Impact of service delivery factors on patient outcomes in emergency general surgery.

BACKGROUND: Emergency general surgery (EGS) is a high-risk process and is associated with poor outcomes and high mortality. This study aimed to evaluate the service delivery factors in a tertiary referral centre which may influence patient outcomes in emergency general surgery. METHODS: Data on consecutive patients undergoing emergency laparotomy in a tertiary referral centre were prospectively collected from July 2017-July 2018. An extensive review of patient charts and IT systems was performed to extract demographic, clinical and care pathway data. Transfers for surgery from within the institution or within the centralised hospital network were recorded. RESULTS: The unadjusted 30-day mortality rate in 163 patients undergoing emergency laparotomy was 13%. On multivariate analysis, 30-day mortality was significantly associated with p-POSSUM predicted mortality (p = 0.003), p-POSSUM predicted morbidity (p = 0.01), SORT mortality (p = 0.004), ICU admission (p = 0.02), ASA grade (p < 0.001) and transfer from non-surgical services (p < 0.001). 19.2% of patients were transferred from a referring hospital for emergency laparotomy. There was no association between inter-hospital transfer and 30-day mortality while increased mortality was observed in patients admitted to non-surgical services who required laparotomy (p < 0.001). CONCLUSION: Inter-hospital transfer for emergency laparotomy was not associated with increased mortality. Increased mortality was observed in patients admitted to non-surgical services who subsequently required emergency laparotomy. Configuration of emergency general surgery services must accommodate safe and effective transfer of patients, both between and within hospitals.

Gastrointestinal stromal tumor metastases to the pituitary: a rare entity.

Gastrointestinal stromal tumors (GISTs) are rare, but represent the most common mesenchymal tumor of the gastrointestinal tract. The paucity of intracranial metastasis makes treatment strategies difficult. This manuscript presents the first documented case report of a GIST that presented clinically with pituitary symptoms due to a pituitary metastasis.

Mucinous Rectal Adenocarcinoma Is Associated with a Poor Response to Neoadjuvant Chemoradiotherapy: A Systematic Review and Meta-analysis.

BACKGROUND: Mucinous adenocarcinoma represents a potentially poor prognostic subgroup of rectal cancer. A consensus on the effect of mucinous cancer on outcomes following neoadjuvant chemoradiotherapy and curative resection for rectal cancer has not been reached. OBJECTIVE: The aim of the current study is to use meta-analytical techniques to assess the association between mucinous histology and response to neoadjuvant chemoradiotherapy in rectal cancer. DATA SOURCES: A comprehensive literature search of PubMed, Embase, and The Cochrane Library was performed. STUDY SELECTION: All studies examining the effect of mucinous histology on chemotherapeutic response in rectal cancer were included. INTERVENTIONS: No direct interventions were performed. MAIN OUTCOME MEASURES: Outcomes of mucinous rectal adenocarcinoma were compared with nonmucinous tumors by using random-effects methods to analyze data. Data are presented as ORs with 95% CIs. The main outcomes measured were the rates of pathological complete response, tumor and nodal downstaging, positive resection margin rate, local recurrence, and overall mortality. RESULTS: Eight comparative series describing outcomes in 1724 patients were identified, 241 had mucinous tumors (14%). Mucinous tumors had a reduced rate of pathological complete response (OR, 0.078; 95% CI, 0.015-0.397; p = 0.002) and tumor downstaging (OR, 0.318; 95% CI, 0.185-0.547; p < 0.001) following neoadjuvant chemoradiotherapy with an increased rate of positive resection margin (OR, 5.018; 95% CI, 3.224-7.810; p < 0.001) and poorer overall survival (OR, 1.526; 95% CI, 1.060-2.198; p = 0.023) following resection. Mucin expression did not significantly affect nodal downstaging (OR, 0.706; 95% CI, 0.295-1.693; p = 0.435) or local recurrence (OR, 1.856; 95% CI, 0.933-3.693; p = 0.078). There was no across-study heterogeneity for any end point. LIMITATIONS: Most studies were retrospectively designed, and there were variations in patient populations and duration of follow-up. CONCLUSIONS: Mucinous rectal adenocarcinoma represents a biomarker for poor response to preoperative chemoradiotherapy and is an adverse prognostic indicator.

Calnexin, an ER stress-induced protein, is a prognostic marker and potential therapeutic target in colorectal cancer.

BACKGROUND: Colorectal cancer (CRC) is a leading cause of cancer mortality in the Western world and commonly treated with genotoxic chemotherapy. Stress in the endoplasmic reticulum (ER) was implicated to contribute to chemotherapeutic resistance. Hence, ER stress related protein may be of prognostic or therapeutic significance. METHODS: The expression levels of ER stress proteins calnexin, calreticulin, GRP78 and GRP94 were determined in n = 23 Stage II and III colon cancer fresh frozen tumour and matched normal tissue samples. Data were validated in a cohort of n = 11 rectal cancer patients treated with radiochemotherapy in the neoadjuvant setting. The calnexin gene was silenced using siRNA in HCT116 cells. RESULTS: There were no increased levels of ER stress proteins in tumour compared to matched normal tissue samples in Stage II or III CRC. However, increased calnexin protein levels were predictive of poor clinical outcome in the patient cohort. Data were validated in the rectal cancer cohort treated in the neoadjuvant setting. Calnexin gene-silencing significantly reduced cell survival and increased cancer cell susceptibility to 5FU chemotherapy. CONCLUSION: Increased tumour protein levels of calnexin may be of prognostic significance in CRC, and calnexin may represent a potential target for future therapies.

Targeting the 19S proteasomal subunit, Rpt4, for the treatment of colon cancer.

Deregulation of the ubiquitin-proteasome pathway has been frequently observed in a number of malignancies. Using quantitative Western blotting of normal and matched tumour tissue, we here identified a significant increase in the 19S proteasome subunit Rpt4 in response to chemoradiation in locally advanced rectal cancer patients with unfavourable outcome. We therefore explored the potential of Rpt4 reduction as a therapeutic strategy in colorectal cancer (CRC). Utilizing siRNA to down regulate Rpt4 expression, we show that silencing of Rpt4 reduced proteasomal activity and induced endoplasmic reticulum stress. Gene silencing of Rpt4 also inhibited cell proliferation, reduced clonogenic survival and induced apoptosis in HCT-116 colon cancer cells. We next developed a cell penetrating peptide-based nanoparticle delivery system to achieve in vivo gene silencing of Rpt4. Administration of Rpt4 siRNA nanoparticles reduced tumour growth and improved survival in a HCT-116 colon cancer xenograft tumour model in vivo. Collectively, our data suggest that inhibition of Rpt4 represents a novel strategy for the treatment of CRC.

A virtual outpatient department provides a satisfactory patient experience following endoscopy.

PURPOSE: The purpose of this study was to investigate telephone follow-up of post-endoscopy patients as an alternative to attendance at the outpatient department. METHODS: Access to outpatient appointments is often a target for improvement in healthcare systems. Increased outpatient clinic capacity is not feasible without investment and extra manpower in an already constrained service. Outpatient attendance was audited at a busy colorectal surgical service. A subset of patients appropriate for follow-up in a "virtual outpatient department" (VOPD) were identified. A pilot study was designed and involved telephone follow-up of low-risk endoscopic procedures. Patient satisfaction was assessed using the Medical Interview Satisfaction Scale (MISS), which is a standardised survey of patient satisfaction with healthcare experiences. This was conducted via anonymous questionnaire at the end of the study. RESULTS: Of a total of 166 patients undergoing endoscopy in the time period, 79 were prospectively recruited to VOPD follow-up based on eligibility criteria. Overall, 67 (84.8 %) were successfully followed up by telephone consultation; nine patients (11.4 %) were contacted by mail. The remaining three patients (3.8 %) were brought back to the OPD. Patients recruited were more likely to be younger (55.82 ± 14.96 versus 60.78 ± 13.97 years, P = 0.029) and to have had normal examinations (49.4 versus 31.0 %, χ (2) = 5.070, P = 0.025). Nearly three quarters of patients responded to the questionnaire. The mean scores for all four aspects of the MISS were satisfactory, and overall patients were satisfied with the VOPD experience. CONCLUSION: VOPD is a target for improved healthcare provision, with improved efficiency and a high patient satisfaction rate.

Clinical application of a systems model of apoptosis execution for the prediction of colorectal cancer therapy responses and personalisation of therapy.

OBJECTIVE: Key to the clinical management of colorectal cancer is identifying tools which aid in assessing patient prognosis and determining more effective and personalised treatment strategies. We evaluated whether an experimental systems biology strategy which analyses the susceptibility of cancer cells to undergo caspase activation can be exploited to predict patient responses to 5-fluorouracil-based chemotherapy and to case-specifically identify potential alternative targeted treatments to reactivate apoptosis. DESIGN: We quantified five essential apoptosis-regulating proteins (Pro-Caspases 3 and 9, APAF-1, SMAC and XIAP) in samples of Stage II (n = 13) and III (n=17) tumour and normal colonic (n = 8) tissue using absolute quantitative immunoblotting and employed systems simulations of apoptosis signalling to predict the susceptibility of tumour cells to execute apoptosis. Additional systems analyses assessed the efficacy of novel apoptosis-inducing therapeutics such as XIAP antagonists, proteasome inhibitors and Pro-Caspase-3-activating compounds in restoring apoptosis execution in apoptosis-incompetent tumours. RESULTS: Comparisons of caspase activity profiles demonstrated that the likelihood of colorectal tumours to undergo apoptosis decreases with advancing disease stage. Systems-level analysis correctly predicted positive or negative outcome in 85% (p=0.004) of colorectal cancer patients receiving 5-fluorouracil based chemotherapy and significantly outperformed common uni- and multi-variate statistical approaches. Modelling of individual patient responses to novel apoptosis-inducing therapeutics revealed markedly different inter-individual responses. CONCLUSIONS: Our study represents the first proof-of-concept example demonstrating the significant clinical potential of systems biology-based approaches for predicting patient outcome and responsiveness to novel targeted treatment paradigms.

Analyzing proteasomal subunit expression reveals Rpt4 as a prognostic marker in stage II colorectal cancer.

Colorectal cancer is a leading cause of cancer-related deaths worldwide. Early diagnosis and treatment of colorectal cancer is the key to improving survival rates and as such a need exists to identify patients who may benefit from adjuvant chemotherapy. The dysregulation of the ubiquitin-proteasome system (UPS) has been implicated in oncogenesis and cancer cell survival, and proteasome inhibitors are in clinical use for a number of malignancies including multiple myeloma. In our study, we examined the protein expression of several key components of the UPS in colorectal cancer using immunohistochemistry to determine expression levels of ubiquitinylated proteins and the proteasomal subunits, 20S core and Rpt4 in a cohort of 228 patients with colon cancer. Multivariate Cox analysis revealed that neither the intensity of either ubiquitinylated proteins or the 20S core was predictive in either Stage II or III colon cancer for disease free survival or overall survival. In contrast, in Stage II patients increased Rpt4 staining was significantly associated with disease free survival (Cox proportional hazard ratio 0.605; p = 0.0217). Our data suggest that Rpt4 is an independent prognostic variable for Stage II colorectal cancer and may aid in the decision of which patients undergo adjuvant chemotherapy.