Management of early oesophageal cancer: An overview.

The incidence of esophageal cancer, namely the adenocarcinoma subtype, continues to increase exponentially on an annual basis. The indolent nature of the disease renders a significant proportion inoperable at first presentation, however, with the increased utilisation of endoscopy, many early lesions are now being identified which are suitable for endotherapeutic approaches. This article details the options available for dealing with early esophageal cancer by endoscopic mean obviating the need for surgery thereby avoiding the potential morbidity and mortality of such intervention.

The use of radiomic analysis of magnetic resonance imaging findings in predicting features of early osteoarthritis of the knee-a systematic review and meta-analysis.

The primary aim of this study was to systematically review current literature evaluating the use of radiomics in establishing the role of magnetic resonance imaging (MRI) findings in native knees in predicting features of osteoarthritis (OA). A systematic review was performed with respect to PRISMA guidelines in search of studies reporting radiomic analysis of magnetic resonance imaging (MRI) to analyse patients with native knee OA. Sensitivity and specificity of radiomic analyses were included for meta-analysis. Following our initial literature search of 1271 studies, only 5 studies met our inclusion criteria. This included 1730 patients (71.5% females) with a mean age of 55.4 ± 15.6 years (range 24-66). The mean RQS of included studies was 16.6 (11-21). Meta-analysis demonstrated the pooled sensitivity and specificity for MRI in predicting features of OA in patients with native knees were 0.74 (95% CI 0.71, 0.78) and 0.85 (95% CI 0.83, 0.87), respectively. The results of this systematic review suggest that the high sensitivities and specificity of MRI-based radiomics may represent potential biomarker in the early identification and classification of native knee OA. Such analysis may inform surgeons to facilitate earlier non-operative management of knee OA in the select pre-symptomatic patients, prior to clinical or radiological evidence of degenerative change.

Tumour budding as a prognostic biomarker in biopsies and resections of neoadjuvant-treated rectal adenocarcinoma.

BACKGROUND: Tumour budding (TB) is a marker of tumour aggressiveness which, when measured in rectal cancer resection specimens, predicts worse outcomes and response to neoadjuvant therapy. We investigated the utility of TB assessment in the setting of neoadjuvant treatment. METHODS AND RESULTS: A single-centre, retrospective cohort study was conducted. TB was assessed using the hot-spot International Tumour Budding Consortium (ITBCC) method and classified by the revised ITBCC criteria. Haematoxylin and eosin (H&E) and AE1/AE3 cytokeratin (CK) stains for ITB (intratumoural budding) in biopsies with PTB (peritumoural budding) and ITB (intratumoural budding) in resection specimens were compared. Logistic regression assessed budding as predictors of lymph node metastasis (LNM). Cox regression and Kaplan-Meier analyses investigated their utility as a predictor of disease-free (DFS) and overall (OS) survival. A total of 146 patients were included; 91 were male (62.3%). Thirty-seven cases (25.3%) had ITB on H&E and 79 (54.1%) had ITB on CK assessment of biopsy tissue. In univariable analysis, H&E ITB [odds (OR) = 2.709, 95% confidence interval (CI) = 1.261-5.822, P = 0.011] and CK ITB (OR = 2.165, 95% CI = 1.076-4.357, P = 0.030) predicted LNM. Biopsy-assessed H&E ITB (OR = 2.749, 95% CI = 1.258-6.528, P = 0.022) was an independent predictor of LNM. In Kaplan-Meier analysis, ITB identified on biopsy was associated with worse OS (H&E, P = 0.003, CK: P = 0.009) and DFS (H&E, P = 0.012; CK, P = 0.045). In resection specimens, CK PTB was associated with worse OS (P = 0.047), and both CK PTB and ITB with worse DFS (PTB, P = 0.014; ITB: P = 0.019). In multivariable analysis H&E ITB predicted OS (HR = 2.930, 95% CI = 1.261-6.809) and DFS (HR = 2.072, 95% CI = 1.031-4.164). CK PTB grading on resection also independently predicted OS (HR = 3.417, 95% CI = 1.45-8.053, P = 0.005). CONCLUSION: Assessment of TB using H&E and CK may be feasible in rectal cancer biopsy and post-neoadjuvant therapy-treated resection specimens and is associated with LNM and worse survival outcomes. Future management strategies for rectal cancer might be tailored to incorporate these findings.

Monopolar diathermy versus a vessel-sealing device for reducing postoperative drain output after simple mastectomy: randomized clinical trial.

BACKGROUND: Electrosurgical devices are commonly used during mastectomy for simultaneous dissection and haemostasis, and can provide potential benefits regarding vessel and lymphatic ligation. The aim of this prospective RCT was to assess whether using a vessel-sealing device (LigaSure™) improves perioperative outcomes compared with monopolar diathermy when performing simple mastectomy. METHODS: Patients were recruited prospectively and randomized in a 1 : 1 manner to undergo simple mastectomy using either LigaSure™ or conventional monopolar diathermy at a single centre. The primary outcome was the number of days the drain remained in situ after surgery. Secondary outcomes of interest included operating time and complications. RESULTS: A total of 86 patients were recruited (42 were randomized to the monopolar diathermy group and 44 were randomized to the LigaSure™ group). There was no significant difference in the mean number of days the drain remained in situ between the monopolar diathermy group and the LigaSure™ group (7.75 days versus 8.23 days; P = 0.613) and there was no significant difference in the mean total drain output between the monopolar diathermy group and the LigaSure™ group (523.50 ml versus 572.80 ml; P = 0.694). In addition, there was no significant difference in the mean operating time between the groups, for simple mastectomy alone (88.25 min for the monopolar diathermy group versus 107.20 min for the LigaSure™ group; P = 0.078) and simple mastectomy with sentinel lymph node biopsy (107.20 min for the monopolar diathermy group versus 114.40 min for the LigaSure™ group; P = 0.440). CONCLUSION: In this double-blinded single-centre RCT, there was no difference in the total drain output or the number of days the drain remained in situ between the monopolar diathermy group and the LigaSure™ group. REGISTRATION NUMBER: EudraCT 2018-003191-13 BEAUMONT HOSPITAL REC 18/66.

Primary splenic abscess in an adult female patient: a case report.

BACKGROUND: Primary splenic abscess is rare and typically presents in patients who are immunocompromised. We present a case of a 47-year-old apparently immunocompetent female patient who was diagnosed with primary splenic abscess from a Salmonella Typhimurium infection following emergency laparotomy. CASE PRESENTATION: A 47-year-old female patient presented with subjective fever and severe epigastric and left flank pain. She was treated empirically with intravenous piperacillin/tazobactam and gentamicin and was resuscitated with intravenous crystalloid infusion. A radiological diagnosis of splenic infarct secondary to splenic artery aneurysm superimposed with splenic abscess was presumed, however at emergency laparotomy, primary splenic abscess was identified. This abscess had eroded the left hemidiaphragm and had ruptured the splenic capsule leading to intra-abdominal pus in the pelvis which on culture grew Salmonella Typhimurium. A splenectomy and primary repair of the left hemidiaphragm were performed, with postoperative pancreatitis diagnosed following the procedure. After intensive care treatment, this patient made a full recovery. CONCLUSION: This case of primary splenic abscess was treated successfully with a combination of surgery (i.e.: splenectomy and surgical drainage), prolonged antimicrobial therapy, and intensive care in the perioperative period.

Evaluating the Impact of Enhanced Recovery After Surgery Protocols on Surgical Outcomes Following Bariatric Surgery-A Systematic Review and Meta-analysis of Randomised Clinical Trials.

BACKGROUND: Enhanced recovery after surgery (ERAS) programmes are evidence-based care improvement processes for surgical patients, which are designed to decrease the impact the anticipated negative physiological cascades following surgery. AIM: To perform a systematic review and meta-analysis of randomised clinical trials (RCTs) to evaluate the impact of ERAS protocols on outcomes following bariatric surgery compared to standard care (SC). METHODS: A systematic review was performed in accordance with PRISMA guidelines. Meta-analysis was performed using Review Manager version 5.4 RESULTS: Six RCTs including 740 patients were included. The mean age was 40.2 years, and mean body mass index was 44.1 kg/m2. Overall, 54.1% underwent Roux-en-Y gastric bypass surgery (400/740) and 45.9% sleeve gastrectomy (340/700). Overall, patients randomised to ERAS programmes had a significant reduction in nausea and vomiting (odds ratio (OR): 0.42, 95% confidence interval (CI): 0.19-0.95, P = 0.040), intraoperative time (mean difference (MD): 5.40, 95% CI: 3.05-7.77, P < 0.001), time to mobilisation (MD: - 7.78, 95% CI: - 5.46 to - 2.10, P < 0.001), intensive care unit stay (ICUS) (MD: 0.70, 95% CI: 0.13-1.27, P = 0.020), total hospital stay (THS) (MD: - 0.42, 95% CI: - 0.69 to - 0.16, P = 0.002), and functional hospital stay (FHS) (MD: - 0.60, 95% CI: - 0.98 to - 0.22, P = 0.002) compared to those who received SC. CONCLUSION: ERAS programmes reduce postoperative nausea and vomiting, intraoperative time, time to mobilisation, ICUS, THS, and FHS compared to those who received SC. Accordingly, ERAS should be implemented, where feasible, for patients indicated to undergo bariatric surgery. Trial registration International Prospective Register of Systematic Reviews (PROSPERO - CRD42023434492.

Implications of Highly Penetrant Genetic Variants on Breast Surgery.

It seems the most probable beneficiaries from the molecular era are those harboring hereditary genetic variants, which are responsible for 5% to 10% of all breast cancer diagnoses. There are several key implications of such variants on clinical practice, from expedited anticipation of primary cancer diagnoses, which can have their risk mitigated by risk reduction surgery, to pragmatism surrounding the management of male breast cancer patients. This communication discusses the implications of highly penetrant (or pathogenic) hereditary variants in contemporary breast surgery practice.

Evaluating analgesia strategies in patients who have undergone oesophagectomy-a systematic review and network meta-analysis of randomised clinical trials.

Optimal pain control following esophagectomy remains a topic of contention. The aim was to perform a systematic review and network meta-analysis (NMA) of randomized clinical trials (RCTs) evaluating the analgesia strategies post-esophagectomy. A NMA was performed according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA)-NMA guidelines. Statistical analysis was performed using Shiny and R. Fourteen RCTs which included 565 patients and assessed nine analgesia techniques were included. Relative to systemic opioids, thoracic epidural analgesia (TEA) significantly reduced static pain scores at 24 hours post-operatively (mean difference (MD): -13.73, 95% Confidence Interval (CI): -27.01-0.45) (n = 424, 12 RCTs). Intrapleural analgesia (IPA) demonstrated the best efficacy for static (MD: -36.2, 95% CI: -61.44-10.96) (n = 569, 15 RCTs) and dynamic (MD: -42.90, 95% CI: -68.42-17.38) (n = 444, 11 RCTs) pain scores at 48 hours. TEA also significantly reduced static (MD: -13.05, 95% CI: -22.74-3.36) and dynamic (MD: -18.08, 95% CI: -31.70-4.40) pain scores at 48 hours post-operatively, as well as reducing opioid consumption at 24 hours (MD: -33.20, 95% CI: -60.57-5.83) and 48 hours (MD: -42.66, 95% CI: -59.45-25.88). Moreover, TEA significantly shortened intensive care unit (ICU) stays (MD: -5.00, 95% CI: -6.82-3.18) and time to extubation (MD: -4.40, 95% CI: -5.91-2.89) while increased post-operative forced vital capacity (MD: 9.89, 95% CI: 0.91-18.87) and forced expiratory volume (MD: 13.87, 95% CI: 0.87-26.87). TEA provides optimal pain control and improved post-operative respiratory function in patients post-esophagectomy, reducing ICU stays, one of the benchmarks of improved post-operative recovery. IPA demonstrates promising results for potential implementation in the future following esophagectomy.

Evaluating the safety profile of anti-platelet therapy in patients undergoing elective inguinal hernia repair: a systematic review and meta-analysis.

INTRODUCTION: There remains no consensus surrounding the safety of prescribing anti-platelet therapies (APT) prior to elective inguinal hernia repair (IHR). AIMS: To perform a systematic review and meta-analysis evaluating the safety profile of APT use in patients indicated to undergo elective IHR. 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: Five studies including outcomes in 344 patients were included. Of these, 65.4% had APT discontinued (225/344), and 34.6% had APT continued (119/344). The majority of included patients were male (94.1%, 288/344). When continuing or discontinuing APT, there was no significant difference in overall haemorrhage rates (odds ratio (OR): 1.86, 95% confidence interval (CI): 0.29-11.78, P = 0.130) and in sensitivity analysis using only RCT data (OR: 0.63, 95% CI: 0.03-12.41, P = 0.760). Furthermore, there was no significant difference in reoperation rates (OR: 6.27, 95% CI: 0.72-54.60, P = 0.590); however, a significant difference was observed for readmission rates (OR: 5.67, 95% CI: 1.33-24.12, P = 0.020) when APT was continued or stopped pre-operatively. There was no significant difference in the estimated blood loss, intra-operative time, transfusion of blood products, rates of complications, cerebrovascular accidents, myocardial infarctions, or mortality observed. CONCLUSION: This study illustrates the safety of continuing APT pre-operatively in patients undergoing elective IHR, with similar rates of haemorrhage, reoperation, and readmission observed. Clinical trials with larger patient recruitment will be required to fully establish the safety profile of prescribing APT in the pre-operative setting prior to elective IHR.

Evaluating mesh fixation techniques for ventral hernia repair: A systematic review and network meta-analysis of randomised control trials.

INTRODUCTION: There is uncertainty regarding the optimal mesh fixation techniques for laparoscopic ventral and incisional hernia repair. AIM: To perform a systematic review and network meta-analysis of randomised control trials (RCTs) to investigate the advantages and disadvantages associated with absorbable tacks, non-absorbable tacks, non-absorbable sutures, non-absorbable staples, absorbable synthetic glue, absorbable sutures and non-absorbable tacks, and non-absorbable sutures and non-absorbable tacks. METHODS: A systematic review was performed as per PRISMA-NMA guidelines. Odds ratios (ORs) and mean differences (MDs) were extracted to compare the efficacy of the surgical approaches. RESULTS: Nine RCTs were included with 707 patients. Short-term pain was significantly reduced in non-absorbable staples (MD; -1.56, confidence interval (CI); -2.93 to -0.19) and non-absorbable sutures (MD; -1.00, CI; -1.60 to -0.40) relative to absorbable tacks. Recurrence, length of stay, operative time, conversion to open surgery, seroma and haematoma formation were unaffected by mesh fixation technique. CONCLUSION: Short-term post-operative pain maybe reduced by the use of non-absorbable sutures and non-absorbable staples. There is clinical equipoise between each modality in relation to recurrence, length of stay, and operative time.

Readmission rates following major colorectal surgery.

BACKGROUND: Readmissions following colorectal surgery (CRS) have negative clinical, psychological and financial implications. Identifying patients at risk of readmission remains challenging. AIMS: To determine factors predictive of those likely to require readmission at 40-days following major CRS and to identify novel strategies capable of reducing readmissions. METHODS: Consecutive patients were studied from a prospectively maintained database. All patients were operated on by a single surgeon in a high-volume centre. Where applicable, photography was recorded by patients and emailed directly to the institutional email of the consultant surgeon. Data was recorded and analysed using descriptive statistics. RESULTS: 515 patients were included over a 15-year period (2007-2022). The mean age at surgery was 64 years (18-93). The majority of patients were male (56.9%, n=293) and underwent cancer surgery (58.2%, n=299). Overall, 55 patients were readmitted within 40 days of major CRS (10.7%). Patients with pre-treatment diagnoses of heart failure (P=0.012), ischemic heart disease (P=0.002), renal impairment (P<0.001), atrial fibrillation (P=0.006), hypercholesterolemia (P=0.001), asthma (P=0.013) and hypertension (P=0.001) were more likely to require readmission. The majority of patients were readmitted for definitive management of surgical site issues (SSIs) (43.7% n=24). Other reasons included bowel obstruction (9.1%, n=5), pelvic sepsis (7.3%, n=4) and gastrointestinal upset (7.3%, n=4). CONCLUSION: This series demonstrated that patients with cardiopulmonary comorbidities were more likely to be readmitted following major CRS and most readmissions are SSI related. Readmissions for SSIs can be reduced by patients sending photography to the treating surgeon which could reduce readmissions and A&E attendances.

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 utility of robotic axillary lymph node dissection in patients with invasive breast cancer: a systematic review.

Robot-assisted axillary lymph node dissection (RALND) has been proposed to improve surgical and oncological outcomes for patients with breast cancer. To perform a systematic review of current literature evaluating RALND in patients with invasive breast cancer. A systematic search was performed in accordance with the PRISMA guidelines. Studies outlining outcomes following RALND were included. Two studies involving 92 patients were included in this review. Of these, 41 underwent RALND using the da Vinci© robotic system (44.57%), and 51 underwent conventional axillary lymph node dissection (CALND) (55.43%). There was no significant difference observed with respect to intra-operative blood loss or duration of procedure in those undergoing CALND and RALND (P > 0.050). One study reported a significant difference in lymphoedema rates in support of RALND (6.67% vs 26.67%, P = 0.038). Overall, data in relation to postoperative fat necrosis (10.00% vs 33.33%, P = 0.028), wound infection rates (3.33% vs. 20.00%, P = 0.044), and wound ≤ 40 mm in length (63.63% vs. 19.05%, P = 0.020) supported RALND. Oncological outcomes were only reported in one of the studies, which concluded that there was no local or metastatic recurrence in either group at 3-month follow-up. These provisional results support RALND as a safe alternative to CALND. Notwithstanding, the paucity of data limits the robustness of conclusions which may be drawn surrounding the adoption of RALND as the standard of care. Further high-quality studies are required to ratify these findings.

Comparing neoadjuvant therapy followed by local excision to total mesorectal excision in the treatment of early stage rectal cancer: a systematic review and meta-analysis of randomised clinical trials.

INTRODUCTION: Total mesorectal excision (TME) is the standard-of-care in early, clinical stage (cT2-3 N0 M0) rectal cancer. Local excision (LE) may be an alternative after adequate response to neoadjuvant therapy (NAT), with either long-course chemoradiotherapy (nCRT) or short-course radiotherapy (SCRT), as a means of preserving the rectum and potentially obviating the morbidity of TME. METHODS: A systematic review was performed according to PRISMA guidelines for studies that randomly assigned patients with cT2-3 N0 M0 rectal cancer to either NAT + LE or TME that reported radiologic, oncologic, surgical, and morbidity outcomes. RESULTS: A total of 4 RCTs comprise 462 patients (232 patients receiving NAT + LE; nCRT n = 205; SCRT n = 27) and 230 undergoing TME, respectively. NAT compliance was 98.86%. The rate of early completion TME in the NAT + LE group was 22.3%, while the proportion of patients achieving durable organ preservation was 75.4% at mean follow-up of 5.6 years. There was no difference in disease-free survival (DFS) (HR [hazard ratio] 1.19; 95% CI 0.95, 1.49; p = 0.13) or overall survival (OS) (HR 0.94; 95% CI 0.72, 1.23; p = 0.63]) according to the assigned treatment arm. The local recurrence rate (LRR) (HR 1.22; 95% CI 0.5-3.02; p = 0.66) and distant metastases (HR 0.92; 95% CI 0.45, 1.90; p = 0.82) were also comparable between the groups. There was a significant reduction in major (OR 0.45; 95% CI 0.21, 0.95; p = 0.04) and minor morbidity (OR 0.45; 95% CI 0.24, 0.85; p = 0.01) for patients undergoing NAT + LE. Overall stoma formation was decreased in the NAT + LE group (OR 0.03; 95% CI 0.0, 0.23; p ≤ 0.00001). CONCLUSION: NAT + LE reduces adverse effects of TME, without any compromise in oncological outcomes, and the potential for an organ preserving strategy should be discussed with patients with T2-3N0 rectal cancers prior to treatment.

Surgical management strategies for colorectal malignancies of the splenic flexure - A systematic review and network meta-analysis.

BACKGROUND: Extended right hemicolectomy (ERHC) or left hemicolectomy (LHC) are accepted as the standard-of-care for colonic tumours of the splenic flexure. Lymphatic drainage at this site is poorly defined and subject to significant heterogeneity. Nevertheless, emerging evidence demonstrates the potential oncological safety of segmental splenic flexure colectomy (SFC). AIM: To perform a systematic review and network meta-analysis (NMA) to compare outcomes following ERHC, LHC and SFC for splenic flexure tumours (SFTs). METHODS: A systematic review was performed as per PRISMA guidelines. NMA was performed using R Shiny and Netmeta packages. RESULTS: A total of 13 studies, involving 6176 patients (ERHC n = 785; LHC n = 1527; SFC n = 3864) were included in the NMA. There was no difference in overall survival (OS) (SFC vs LHC Hazard Ratio [HR] 1.0, 95% Credible Interval [CrI] 0.76,1.34; SFC vs ERHC HR 1.18, 95% CrI 0.85,1.58) between the groups. SFC had a shorter operation time (Mean 176.37 min; Mean Difference [MD] SFC vs LHC 20.34 min 95% CrI 10.9, 29.97; SFC vs ERHC MD 22.19 95% CrI 11.09, 33.29) but also had a lower average lymph node yield (LNY) compared with ERHC (MD 7.15, 95% CrI 5.71, 8.60). ERHC had a significantly higher incidence of post-operative ileus (Odds Ratio [OR] 3.47, 95% CrI 1.11, 10.84). There was also no difference observed for minimally invasive approaches, anastomotic leak rate, perioperative mortality, reoperation rates or length of stay. CONCLUSIONS: While SFC may allow for reduced operative duration and improved bowel function postoperatively. SFC, LHC, ERHC are all acceptable approaches for curative resection of cancers of the splenic flexure, with no difference in OS observed. Thus, surgeon preference and candidate-specific factors will likely determine the management of SFTs.

The Effects of Pre-existing Mood Disorders on Patient-Reported Outcomes After Arthroscopic Rotator Cuff Repair: A Systematic Review and Meta-analysis.

BACKGROUND: The purpose of this study was to systematically review the literature to evaluate the effect of pre-existing mood disorders on patient-reported outcomes after arthroscopic rotator cuff repair (ARCR). METHODS: Two independent reviewers performed a literature search using the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines using PubMed, Embase, Cochrane Library, and Scopus databases. Only studies which grouped as either having a pre-existing mood disorder (namely anxiety and/or depression) or not and evaluated patient-reported outcomes following ARCR procedures were considered for inclusion. Meta-analysis was performed on outcomes using RevMan, with a p-value <0.05 being deemed statistically significant. RESULTS: Our search found 8 studies including 1,166 shoulders (58.9% males), with an average age of 57.7 ± 3.2 years (21-81) and mean follow-up of 20.8 ± 16.7 months (3-77) which met our inclusion criteria. There were a total of 262 patients (22.5%; mean age 59.9 ± 1.4 years) with pre-existing anxiety and/or depression and 904 patients (77.5%; mean age 59.7 ± 1.7 years) in the control group who underwent ARCR, respectively. Meta-analysis found significantly lower American Shoulder and Elbow Surgeons scores as well as Simple Shoulder Test scores in patients with pre-existing anxiety and/or depression when compared with a control (mean difference [MD] -7.92 [-9.45, -6.40], p < 0.0001, I2 = 0%; MD -1.56 [-2.54, -0.59], p = 0.002, I2 = 80%, respectively) In addition, meta-analysis demonstrated significantly higher Visual Analog Scale scores for pain in patients with pre-existing anxiety and/or depression when compared with a control (MD 0.70 [0.02, 1.38], p = 0.04, I2 = 71%). Furthermore, meta-analysis performed found that ARCR resulted in significant changes in the rates of reported anxiety and/or depression in patients with pre-existing anxiety and/or depression (MD 4.06[-2.47, 6.68], p < 0.0001, I2 = 0%). CONCLUSION: Our review found that patients with pre-existing mood disorders were significantly more likely to report higher rates of postoperative pain and poorer functional outcomes following ARCR procedures, when compared with controls without mood disorders. Therefore, the presence of pre-existing anxiety and/or depression warrants consideration in the management paradigm for patients with rotator cuff tears. More optimistically, however, ARCR resulted in significant improvements in anxiety and/or depressive symptoms postoperatively. LEVEL OF EVIDENCE: Level III; systematic review of retrospective comparative studies. See Instructions for Authors for a complete description of levels of evidence.

Biological Implications of MicroRNAs as Regulators and Biomarkers of Therapeutic Toxicities in Breast Cancer.

Contemporary breast cancer management includes surgical resection combined with a multimodal approach, including chemotherapy, radiotherapy, endocrine therapy, and targeted therapies. Breast cancer treatment is now personalised in accordance with disease and host factors, which has translated to enhanced outcomes for the vast majority of patients. Unfortunately, the treatment of the disease involves patients developing treatment-induced toxicities, with cardiovascular and metabolic side effects having negative implications for long-term quality-of-life metrics. MicroRNAs (miRNAs) are a class of small non-coding ribonucleic acids that are 17 to 25 nucleotides in length, which have utility in modifying genetic expression by working at a post-transcriptional cellular level. miRNAs have involvement in modulating breast cancer development, which is well described, with these biomarkers acting as important regulators of disease, as well as potential diagnostic and therapeutic biomarkers. This review focuses on highlighting the role of miRNAs as regulators and biomarkers of disease, particularly in breast cancer management, with a specific mention of the potential value of miRNAs in predicting treatment-related cardiovascular toxicity.

Circulating microRNAs can predict chemotherapy-induced toxicities in patients being treated for primary breast cancer.

PURPOSE: Prescribing NAC for breast cancer is a pragmatic treatment strategy for several reasons; however, certain patients suffer chemotherapy-induced toxicities. Unfortunately, identifying patients at risk of toxicity often proves challenging. MiRNAs are small non-coding RNA molecules which modulate genetic expression. The aim of this study was to determine whether circulating miRNAs are sensitive biomarkers that can identify the patients likely to suffer treatment-related toxicities to neoadjuvant chemotherapy (NAC) for primary breast cancer. METHODS: This secondary exploratory from the prospective, multicentre translational research trial (CTRIAL ICORG10/11-NCT01722851) recruited 101 patients treated with NAC for breast cancer, from eight treatment sites across Ireland. A predetermined five miRNAs panel was quantified using RQ-PCR from patient bloods at diagnosis. MiRNA expression was correlated with chemotherapy-induced toxicities. Regression analyses was performed using SPSS v26.0. RESULTS: One hundred and one patients with median age of 55 years were recruited (range: 25-76). The mean tumour size was 36 mm and 60.4% had nodal involvement (n = 61) Overall, 33.7% of patients developed peripheral neuropathies (n = 34), 28.7% developed neutropenia (n = 29), and 5.9% developed anaemia (n = 6). Reduced miR-195 predicted patients likely to develop neutropenia (P = 0.048), while increased miR-10b predicted those likely to develop anaemia (P = 0.049). Increased miR-145 predicted those experiencing nausea and vomiting (P = 0.019), while decreased miR-21 predicted the development of mucositis (P = 0.008). CONCLUSION: This is the first study which illustrates the value of measuring circulatory miRNA to predict patient-specific toxicities to NAC. These results support the ideology that circulatory miRNAs are biomarkers with utility in predicting chemotherapy toxicity as well as treatment response.

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.

Minimally Invasive and Open Gastrectomy for Gastric Cancer: A Systematic Review and Network Meta-Analysis of Randomized Clinical Trials.

BACKGROUND AND OBJECTIVES: Optimal surgical management for gastric cancer remains controversial. We aimed to perform a network meta-analysis (NMA) of randomized clinical trials (RCTs) comparing outcomes after open gastrectomy (OG), laparoscopic-assisted gastrectomy (LAG), and robotic gastrectomy (RG) for gastric cancer. METHODS: A systematic search of electronic databases was undertaken. An NMA was performed as per the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA)-NMA guidelines. Statistical analysis was performed using R and Shiny. RESULTS: Twenty-two RCTs including 6890 patients were included. Overall, 49.6% of patients underwent LAG (3420/6890), 46.6% underwent OG (3212/6890), and 3.7% underwent RG (258/6890). At NMA, there was a no significant difference in recurrence rates following LAG (odds ratio [OR] 1.09, 95% confidence interval [CI] 0.77-1.49) compared with OG. Similarly, overall survival (OS) outcomes were identical following OG and LAG (OS: OG, 87.0% [1652/1898] vs. LAG: OG, 87.0% [1650/1896]), with no differences in OS in meta-analysis (OR 1.02, 95% CI 0.77-1.52). Importantly, patients undergoing LAG experienced reduced intraoperative blood loss, surgical incisions, distance from proximal margins, postoperative hospital stays, and morbidity post-resection. CONCLUSIONS: LAG was associated with non-inferior oncological and surgical outcomes compared with OG. Surgical outcomes following LAG and RG superseded OG, with similar outcomes observed for both LAG and RG. Given these findings, minimally invasive approaches should be considered for the resection of local gastric cancer, once surgeon and institutional expertise allows.