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.

Management Strategies for Malignant Left-Sided Colonic Obstruction: A Systematic Review and Network Meta-analysis of Randomized Controlled Trials and Propensity Score Matching Studies.

BACKGROUND: The optimal treatment strategy for left-sided malignant colonic obstruction remains controversial. Emergency colonic resection has been the standard of care; however, self-expanding metallic stenting as a bridge to surgery may offer short-term advantages, although oncological concerns exist. Decompressing stoma may provide a valid alternative, with limited evidence. OBJECTIVE: To perform a systematic review and Bayesian arm random-effects model network meta-analysis comparing the approaches for management of malignant left-sided colonic obstruction. DATA SOURCES: A systematic review of PubMed, Embase, Cochrane Library, and Google Scholar databases was conducted from inception to August 22, 2023. STUDY SELECTION: Randomized controlled trials and propensity score-matched studies. INTERVENTIONS: Emergency colonic resection, self-expanding metallic stent, and decompressing stoma. MAIN OUTCOME MEASURES: Oncologic efficacy, morbidity, successful minimally invasive surgery, primary anastomosis, and permanent stoma rates. RESULTS: Nineteen of 5225 articles identified met our inclusion criteria. Stenting (risk ratio 0.57; 95% credible interval, 0.33-0.79) and decompressing stomas (risk ratio 0.46, 95% credible interval: 0.18-0.92) resulted in a significant reduction in the permanent stoma rate. Stenting facilitated minimally invasive surgery more frequently (risk ratio 4.10; 95% credible interval, 1.45-13.13) and had lower overall morbidity (risk ratio 0.58; 95% credible interval, 0.35-0.86). A pairwise analysis of primary anastomosis rates showed increased stenting (risk ratio 1.40; 95% credible interval, 1.31-1.49) compared with emergency resection. There was a significant decrease in the 90-day mortality with stenting (risk ratio 0.63; 95% credible interval, 0.41-0.95) compared with resection. There were no differences in disease-free and overall survival rates, respectively. LIMITATIONS: There is a lack of randomized controlled trials and propensity score matching data comparing short-term and long-term outcomes for diverting stomas compared to self-expanding metallic stents. Two trials compared self-expanding metallic stents and diverting stomas in left-sided malignant colonic obstruction. CONCLUSIONS: This study provides high-level evidence that a bridge-to-surgery strategy is safe for the management of left-sided malignant colonic obstruction and may facilitate minimally invasive surgery, increase primary anastomosis rates, and reduce permanent stoma rates and postoperative morbidity compared with emergency colonic resection.

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.

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.

Long-term survival in patients with node-positive breast cancer who undergo sentinel lymph node biopsy alone after neoadjuvant chemotherapy: meta-analysis.

BACKGROUND: Sentinel lymph node biopsy (SLNB) after neoadjuvant chemotherapy (NACT) in patients with breast cancer who are initially node-positive but convert to clinically/radiologically node-negative remains controversial. The primary aim was to assess pooled 5-year disease-free (DFS) and overall (OS) survival for patients who are initially node-positive but have a negative SLNB after NACT, and do not proceed to axillary lymph node dissection (ALND). METHODS: The study was performed using PRISMA guidelines. A systematic literature search of relevant databases was conducted. The Der Simonian-Laird and Cochran-Mantel-Haenszel methods were used to calculate weighted pooled estimates for OS and DFS for this group compared with patients who had NACT and proceeded to ALND after a negative or positive SLNB. RESULTS: Seven studies involving 915 patients who had a negative SLNB after NACT were included. Pooled estimates of 5-year DFS and OS in patients with a negative SLNB after NACT were 86 (95 per cent c.i. 82.1 to 90.3) and 93.1 (87.8 to 97.0) per cent respectively. Patients with a positive SLNB who underwent ALND had reduced 5-year DFS (OR 0.49, 95 per cent c.i. 0.35 to 0.69; P < 0.001) and OS (OR 0.41, 0.16 to 1.02; P = 0.06) compared with those who had a negative SLNB after NACT. There were no differences in DFS for patients who had a negative SLNB only compared with those undergoing ALND with a pCR (OR 1.65, 0.71 to 3.79; P = 0.24). CONCLUSION: Patients who are initially node-positive and who achieve a complete clinical/radiological axillary response after NACT with a subsequent negative SLNB have high rates of DFS and OS after 5 years. Patients with residual disease have significantly reduced DFS and further axillary treatment may still be warranted.

Total neoadjuvant therapy versus standard neoadjuvant treatment strategies for the management of locally advanced rectal cancer: network meta-analysis of randomized clinical trials.

BACKGROUND: This study compared the advantages and disadvantages of total neoadjuvant therapy (TNT) strategies for patients with locally advanced rectal cancer, compared with the more traditional multimodal neoadjuvant management strategies of long-course chemoradiotherapy (LCRT) or short-course radiotherapy (SCRT). METHODS: A systematic review and network meta-analysis of exclusively RCTs was undertaken, comparing survival, recurrence, pathological, radiological, and oncological outcomes. The last date of the search was 14 December 2022. RESULTS: In total, 15 RCTs involving 4602 patients with locally advanced rectal cancer, conducted between 2004 and 2022, were included. TNT improved overall survival compared with LCRT (HR 0.73, 95 per cent credible interval 0.60 to 0.92) and SCRT (HR 0.67, 0.47 to 0.95). TNT also improved rates of distant metastasis compared with LCRT (HR 0.81, 0.69 to 0.97). Reduced overall recurrence was observed for TNT compared with LCRT (HR 0.87, 0.76 to 0.99). TNT showed an improved pCR compared with both LCRT (risk ratio (RR) 1.60, 1.36 to 1.90) and SCRT (RR 11.32, 5.00 to 30.73). TNT also showed an improvement in cCR compared with LCRT (RR 1.68, 1.08 to 2.64). There was no difference between treatments in disease-free survival, local recurrence, R0 resection, treatment toxicity or treatment compliance. CONCLUSION: This study provides further evidence that TNT has improved survival and recurrence benefits compared with current standards of care, and may increase the number of patients suitable for organ preservation, without negatively influencing treatment toxicity or compliance.

Relevance of shrinkage versus fragmented response patterns in rectal cancer.

AIMS: Partial response to neoadjuvant chemoradiotherapy (CRT) presents with one of two main response patterns: shrinkage or fragmentation. This study investigated the relevance of these response patterns in rectal cancer, correlation with other response indicators, and outcome. METHODS AND RESULTS: The study included a test (n = 197) and a validation cohort (n = 218) of post-CRT patients with rectal adenocarcinoma not otherwise specified and a partial response. Response patterns were scored by two independent observers using a previously developed three-step flowchart. Tumour regression grading (TRG) was established according to both the College of American Pathologists (CAP) and Dworak classifications. In both cohorts, the predominant response pattern was fragmentation (70% and 74%), and the scoring interobserver agreement was excellent (k = 0.85). Patients with a fragmented pattern presented with significantly higher pathological stage (ypTNM II-IV, 78% versus 35%; P < 0.001), less tumour regression with Dworak (P = 0.004), and CAP TRG (P = 0.005) compared to patients with a shrinkage pattern. As a predictor of prognosis, the shrinkage pattern outperformed the TRG classification and stratified patients better in overall (fragmented pattern, hazard ratio [HR] 2.04, 95% confidence interval [CI] 1.19-3.50, P = 0.008) and disease-free survival (DFS; fragmented pattern, HR 2.50, 95% CI 1.23-5.10, P = 0.011) in the combined cohorts. The multivariable regression analyses revealed pathological stage as the only independent predictor of DFS. CONCLUSIONS: The heterogeneous nature of tumour response following CRT is reflected in fragmentation and shrinkage. In rectal cancer there is a predominance of the fragmented pattern, which is associated with advanced stage and less tumour regression. While not independently associated with survival, these reproducible patterns give insights into the biology of tumour response.

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.

Comparing surgical outcomes of approaches to adrenalectomy - a systematic review and network meta-analysis of randomised clinical trials.

BACKGROUND: No randomised clinical trials (RCTs) have simultaneously compared the safety of open (OA), transperitoneal laparoscopic (TLA), posterior retroperitoneal (PRA), and robotic adrenalectomy (RA) for resecting adrenal tumours. AIM: To evaluate outcomes for OA, TLA, PRA, and RA from RCTs. METHODS: A NMA was performed according to PRISMA-NMA guidelines. Analysis was performed using R packages and Shiny. RESULTS: Eight RCTs with 488 patients were included (mean age: 48.9 years). Overall, 44.5% of patients underwent TLA (217/488), 37.3% underwent PRA (182/488), 16.4% underwent RA (80/488), and just 1.8% patients underwent OA (9/488). The mean tumour size was 35 mm in largest diameter with mean sizes of 44.3 mm for RA, 40.9 mm for OA, 35.5 mm for TLA, and 34.4 mm for PRA (P < 0.001). TLA had the lowest blood loss (mean: 50.6 ml), complication rates (12.4%, 14/113), and conversion to open rates (1.3%, 2/157), while PRA had the shortest intra-operative duration (mean: 94 min), length of hospital stay (mean: 3.7 days), lowest visual analogue scale pain scores post-operatively (mean: 3.7), and was most cost-effective (mean: 1728 euros per case). At NMA, there was a significant increase in blood loss for OA (mean difference (MD): 117.00 ml (95% confidence interval (CI): 1.41-230.00)) with similar blood loss observed for PRA (MD: - 10.50 (95% CI: - 83.40-65.90)) compared to TLA. CONCLUSION: LTA and PRA are important contemporary options in achieving favourable outcomes following adrenalectomy. The next generation of RCTs may be more insightful for comparison surgical outcomes following RA, as this approach is likely to play a future role in minimally invasive adrenalectomy. PROSPERO REGISTRATION: CRD42022301005.

What works best in hiatus hernia repair, sutures alone, absorbable mesh or non-absorbable mesh? A systematic review and network meta-analysis of randomized clinical trials.

Laparoscopic hiatal hernia repair (HHR) and fundoplication is a common low risk procedure providing excellent control of gastro-oesophageal reflux disease and restoring of normal anatomy at the hiatus. HHR may fail, however, resulting in hiatus hernia (HH) recurrence, and the use of tension-free mesh-augmented hernioplasty has been proposed to reduce recurrence. Previous research on this topic has been heterogeneous, including study methods, mesh type used and technique performed. A systematic review and network meta-analysis were carried out. An electronic systematic research was carried out using 'PUBMED', 'EMBASE', 'Medline (OVID)' and 'Web of Science', of articles identifying HHR with suture cruroplasty, non-absorbable mesh (NAM) and absorbable mesh (AM) reinforcement. Eight RCTs with 766 patients were evaluated. NAM had significantly (P < 0.05) lower early recurrence rates (OR: 0.225, 95% CI 0.0342, 0.871) compared with suture repair alone; however, no differences in late recurrences were evident. For AM, no difference in early (0.508, 95% CI 0.0605, 4.81) or late (1.07. 95% CI 0.116, 11.4) recurrence rates were evident compared with the suture only group. Major complication rates were similar in all groups. NAM reinforcement significantly reduced early HH recurrence when compared with sutured cruroplasty alone; however, late recurrence rates were similar with all techniques. Given the limited data in comparing AM with NAM, this study was unable to conclude which composition was significant. We emphasize caution when interpreting small sample size RCTs, and recommend more research with larger randomized studies.

Outcomes of Saphenous Vein Intervention in the Management of Superficial Venous Incompetence: A Systematic Review and Network Meta-analysis.

OBJECTIVE: To determine the most effective modality of intervention to treat saphenous vein insufficiency. SUMMARY OF BACKGROUND DATA: Endovenous therapies have instigated a paradigm shift in the management of superficial venous incompetence. When compared with open surgery, endovenous interventions (foam sclerotherapy, radiofrequency ablation, endovenous laser ablation (EVLA), mechanochemical ablation, and CAE closure) potentially offer reduced morbidity with similar procedural efficacy. METHODS: A systematic review and series of network meta-analyses of randomized controlled trials were performed assessing risks of procedural failure (within 6-weeks) and recurrence (6-weeks to 5-years), defined by ultrasound, between the different modalities of intervention for superficial venous incompetence. Treatment comparisons addressing risks of common adverse events, venous clinical severity score, and pain were also performed. RESULTS: A systematic search identified 51 articles, describing 36 randomized controlled trials, incorporating 7576 limbs. Outcome data on 10 modalities of intervention were analyzed up to 5-year follow-up. CAE resulted in the lowest risk of procedural failure within 6-weeks. Foam sclerotherapy had the highest risk of recurrence while high ligation with stripping (HLS) and Conservatrice Hemodynamique de l'Insuffisance Veineuse en Ambulatoire were ranked best to reduce long-term recurrence. No intervention increased risks of venous thromboembolism and there was minimal difference in morbidity between treatments. All interventions improved venous clinical severity score (range -1.02 to -4.95), however, radiofrequency ablation demonstrated the greatest improvement, followed by EVLA and HLS between 2 to 5-years. EVLA was associated with the highest risk of pain, while mechanochemical ablation offered the least. CONCLUSIONS: Although CAE offered the lowest risk of initial procedural failure, HLS resulted in lower rates of long-term recurrence without considerably increasing morbidity when compared with other endovenous options.

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.

Clinicopathological correlates, oncological impact, and validation of Oncotype DX™ in a European Tertiary Referral Centre.

Oncotype DX™ (ODX) score estimates prognosis and predicts breast cancer recurrence. It also individualizes patient adjuvant chemotherapy prescription in breast cancer. This assay relies on genetic and molecular markers; the clinicopathological phenotype of which are tested routinely. The aim of this study was determine whether clinicopathological and immunohistochemical information predicts ODX recurrence score (RS). Secondly, to assess the impact on adjuvant chemotherapy (AC) and oncological outcome of ODX testing in patients in a European tertiary referral center. Estrogen receptor positive (ER+), human epidermal growth factor receptor-2 negative (HER2-), lymph node negative (LN-), and female breast cancer patients with ODX testing performed between 2007 and 2015 were categorized into low- (<11), intermediate- (11-25), and high-risk (>25) groups. Clinicopathological and immunohistochemical correlates of RS were determined. Predictors of RS were assessed using binary logistic regression. Oncological outcome was assessed using Kaplan-Meier and Cox regression analyses. ODX was performed in 400 consecutive ER+LN- patients. Median follow-up was 74.1 months (3.0-144.4). Low grade (odds ratio [OR]:2.39; 95% confidence interval [CI]:1.04-5.51, p = 0.041) independently predicted low ODX, while high grade (OR:2.04; 95% CI: 1.19-3.49, p = 0.009) and reduced progesterone receptor (PgR) expression (OR: 2.57, 95% CI: 1.42-4.65, p = 0.002) independently predicted high ODX. Omission of AC in intermediate- (p = 0.159) and high-risk (p = 0.702) groups did not negatively impact survival. In conclusion, tumor grade independently predicts low and high RS, while PgR negativity predicts high RS. ODX reduced AC prescription without compromising oncological outcome.

The histopathological and molecular features of breast carcinoma with tumour budding-a systematic review and meta-analysis.

PURPOSE: Tumour budding (TB) is an adverse histological feature in many epithelial cancers. It is thought to represent epithelial-mesenchymal transition, a key step in the metastatic process. The significance of TB in breast carcinoma (BC) remains unclear. The aim of this study is to investigate the relationship between TB and other histological and molecular features of BC. METHODS: A systematic search was performed to identify studies that compared features of BC based on the presence or absence of high-grade TB. Dichotomous variables were pooled as odds ratios (OR) using the Der Simonian-Laird method. Quality assessment of the included studies was performed using the Newcastle-Ottawa scale (NOS). RESULTS: Seven studies with a total of 1040 patients (high-grade TB n = 519, 49.9%; low-grade/absent TB n = 521, 50.1%) were included. A moderate to high risk of bias was noted. The median NOS was 7 (range 6-8). High-grade TB was significantly associated with lymph node metastasis (OR 2.32, 95% c.i. 1.77 to 3.03, P < 0.001) and lymphovascular invasion (OR 3.08, 95% c.i. 2.13 to 4.47, P < 0.001). With regard to molecular subtypes, there was an increased likelihood of high-grade TB in oestrogen (OR 1.66, 95% c.i. 1.21 to 2.29, P = 0.002) and progesterone receptor-positive (OR 1.48, 95% c.i. 1.09 to 2.02, P = 0.01) tumours. In contrast, triple-negative breast cancer had a reduced incidence of high-grade TB (OR 0.46, 95% c.i. 0.30 to 0.72, P = 0.0006). CONCLUSION: High-grade TB is enriched in hormone receptor-positive BC and is associated with known adverse prognostic variables. TB may offer new insights into the metastatic process of BC.

Impact of progesterone receptor status on response to neoadjuvant chemotherapy in estrogen receptor-positive breast cancer patients.

INTRODUCTION: Breast cancer patients respond differently to neoadjuvant chemotherapy(NAC) based on receptor subtype. The aim of this study was to assess the impact of progesterone receptor (PgR) status on response to neoadjuvant chemotherapy (NAC) in estrogen receptor (ER)+, human epidermal growth factor receptor (HER)- breast cancer patients. METHODS: ER+ and HER- patients receiving NAC over a 7-year period (2011-2017) were identified. The primary outcome was breast complete pathological response (pCR) rate. Secondary outcomes included axillary pCR, axillary/breast pCR and complete radiological response (cRR). RESULTS: A total of 203 patients were identified (149 in the ER+, PgR+, and HER- group and 54 in the ER+, PgR-, and HER- group). Compared with the PgR+ group, PgR- patients were significantly associated with breast pCR (31.5% vs 7.4%; χ² test; P < .01). In multivariable analysis, PgR- status (odds ratio [OR], 4.58; 95% confidence interval [CI]: 1.58,13.28; P = .005), radiological size >50 mm (OR, 5.38; 95% CI: 1.07,27.04; P = .04) and grade (OR, 3.52;95% CI: 1.21,10.23;P = .02) were significant predictors of breast pCR. Only PgR- status was a significant predictor of cRR (OR, 6.234; 95% CI: 2.531, 15.355; P < .001). In node positive patients, PgR negativity was associated with a trend towards breast/axillary nodal pCR (22% vs 12.7%; χ² test; P = .055). CONCLUSION: Over 30% of ER+, PgR-, and HER- patients will have a breast pCR after NAC. PgR- is the only significant predictor of breast pCR/cRR in this tumor subtype. ER+, PgR-, and HER- patients should be considered for NAC.

Concomitant vs. Staged Treatment of Varicose Tributaries as an Adjunct to Endovenous Ablation: A Systematic Review and Meta-Analysis.

OBJECTIVE: This review compares the outcomes of both concomitant and staged superficial varicose tributary (SVT) interventions as an adjunct to endovenous truncal ablation. METHODS: A systematic search of Medline through Pubmed, Embase, and the Cochrane Central Register of Controlled Trials was last performed in November 2019. All studies comparing the outcomes of both concomitant and staged treatments for SVT as an adjunct to endovenous truncal ablation were included. Each included study was subject to an evaluation of methodological quality using the Downs and Black assessment tool. Outcomes assessed included rates of re-intervention, complications, and thrombotic events. Quality of life (QOL) and disease severity were also analysed. Data were pooled with a random effects model. RESULTS: Fifteen studies (6 915 limbs) were included for analysis. Included studies were of reasonable methodological quality. Re-intervention rates were significantly lower in the concomitant group (6.3% vs. 36.1%) when compared with staged intervention (relative risk [RR] 0.21 [95% CI 0.07-0.62], p = .004, I2 = 90%, p ≤ .001). Reported complications (RR 1.14 [95% CI 0.67-1.93], p = .64) and rates of deep venous thrombosis (RR 1.41 [95% CI 0.72-2.77] p = .31) were similar in each group. Overall disease severity (Venous Clinical Severity Score) was lower in the concomitant group (-1.16 [95% CI, -1.97- -0.35] p = .005), while QOL, assessed using the Aberdeen Varicose Vein Questionnaire, favoured concomitant treatment when measured at less than three months (weighted mean difference [WMD] -3.6 [95% CI, -7.17- -0.03] p = .050) and between three and 12 months (WMD -1.61 [95% CI, -2.99- -0.23] p = .020). CONCLUSION: Concomitant and staged treatments are safe and effective. Improvements in early disease severity and QOL scores were better in the concomitant group. While meta-analysis suggests that concomitant intervention offers significantly lower rates of re-intervention, studies assessing its merits are subject to some biases. This benefit was not reflected by the randomised trial subgroup analysis, which identified no difference in re-intervention.

Strictureplasty versus bowel resection for the surgical management of fibrostenotic Crohn's disease: a systematic review and meta-analysis.

BACKGROUND: Strictureplasty (SPX) conserves bowel length and minimizes the risk of developing short bowel syndrome in patients undergoing surgery for Crohn's disease (CD). However, SPX may be associated with a higher risk of recurrence compared with bowel resection (BR). AIM: We sought to compare morbidity and recurrence following SPX and BR in patients with fibrostenotic CD. METHODS: A systematic review was performed according to PRISMA and MOOSE guidelines. Observational studies that compared outcomes of CD patients undergoing either SPX or BR were identified. Log hazard ratios (InHR) for recurrence-free survival (RFS) and their standard errors were calculated from Kaplan-Meier plots or Cox regression models and pooled using the inverse variance method. Dichotomous variables were pooled as odds ratios (OR) using the Mantel-Haenszel method. Continuous variables were pooled as weighted mean differences. RESULTS: Twelve studies of 1026 CD patients (SPX n = 444, 43.27%; BR with or without SPX n = 582, 56.72%) were eligible for inclusion. There was an increased likelihood of disease recurrence with SPX than with BR (OR 1.61; 95% CI, 1.03, 2.52; p = 0.04; I2 = 0%). Patients who had a SPX alone had a significantly reduced RFS than those who underwent BR (HR 1.47; 95% CI, 1.08, 2.01; p = 0.02; I2 = 0%). There was no difference in morbidity between the groups (OR 0.58; 95% CI, 0.26, 1.28; p = 0.18; I2 = 0%). CONCLUSION: SPX should only be performed in those patients with Crohn's strictures that are at high risk for short bowel syndrome and intestinal failure; otherwise, BR is the favored surgical technique for the management of fibrostenotic CD.

Endoscopic management versus transanal surgery for early primary or early locally recurrent rectal neoplasms-a systematic review and meta-analysis.

BACKGROUND: Both endoscopic techniques and transanal surgery are viable options that allow organ preservation for early rectal neoplasms. Whilst endoscopic approaches are less invasive and carry less morbidity, it is unclear whether they are as oncologically effective. AIM: To compare endoscopic techniques with transanal surgery in the management of early rectal neoplasms. METHODS: A systematic literature search was performed for randomised and observational studies comparing these techniques. The pre-specified main outcomes measured were en bloc and R0 resection rates and recurrence. Pair-wise meta-analysis was performed. RESULTS: This review included 1044 patients. Transanal surgery had increased R0 resection rates (odds ratio (OR) 2.66; 95% CI 1.64; 4.31; p < 0.001) versus endoscopic management. The latter was associated with higher rates of incomplete resection (OR 2.25; 95% CI 1.14, 4.46; p = 0.02) and further intervention (OR 1.78; 95% CI 1.09, 2.88; p = 0.02). There was no difference in the rates of late recurrence (OR 1.01; 95% CI 0.53, 1.91; p = 0.99) or further major surgery (OR 0.87; 95% CI 0.39, 1.94; p = 0.73) between the groups. Endoscopic treatment was associated with a shorter operating time (weighted mean difference (WMD) - 12.08; 95% CI - 18.97, - 5.19; p < 0.001) and LOS (WMD - 1.94; 95% CI - 2.43, - 1.44; p < 0.001), as well as lower rates of urinary retention post-operatively (OR 0.12; 95% CI 0.02, 0.63; p = 0.01). CONCLUSION: Endoscopic techniques should be favoured in the setting of benign early rectal neoplasms given their decreased morbidity and increased cost-effectiveness. However, where malignancy is suspected transanal surgery should be the preferred option given the superior R0 resection rate.

Meta-analysis of early bowel resection versus initial medical therapy in patient's with ileocolonic Crohn's disease.

BACKGROUND: Early bowel resection (EBR) in ileocolonic Crohn's disease (CD) may be associated with more durable remission compared with initial medical therapy (IMT) even when biologic therapy is included. AIM: To compare the efficacy of EBR versus IMT for ileocolonic CD METHODS: A systematic search was performed to identify studies that compared EBR (performed < 1 year from initial diagnosis) or IMT for the management of ileocolonic CD. Log hazard ratios (InHR) for relapse-free survival (RFS) and their standard errors were calculated from Kaplan-Meier plots and pooled using the inverse-variance method. Dichotomous variables were pooled as odds ratios (OR). Quality assessment of the included studies was performed using the Newcastle-Ottawa (NOS) and Jadad scales. RESULTS: A total of 7 studies with 1863 CD patients (EBR n = 581, 31.2%; IMT n = 1282, 68.8%) were eligible for inclusion. There was a moderate-to-high risk of bias. The median NOS was 8 (range 7-9). There was a reduced likelihood of overall (OR, 0.53; 95% confidence interval (95% CI), 0.34, 0.83; p = 0.005) and surgical (OR, 0.47; 95% CI, 0.24, 0.91; p = 0.03) relapse with EBR. There was also a less requirement for maintenance biologic therapy (OR, 0.24; 95% CI, 0.14, 0.42; p < 0.0001). Patients who underwent EBR had a significantly improved RFS than those who underwent IMT (HR, 0.62; 95% CI, 0.52, 0.73; p < 0.001). There was no difference in morbidity (OR, 1.67; 95% CI, 0.44, 6.36; p = 0.45) between the groups. CONCLUSION: EBR may be associated with less relapse and need for maintenance biologic therapy than IMT. 'Upfront' or early resection may represent a reasonable and cost-effective alternative to biologic therapy, especially in biologic-resistant subpopulations.

Systematic review and meta-analysis comparing primary resection and anastomosis versus Hartmann's procedure for the management of acute perforated diverticulitis with generalised peritonitis.

BACKGROUND: Surgical strategies for acute perforated diverticulitis with generalised peritonitis remain controversial. This study aimed to meta-analyse trials comparing primary resection and anastomosis (PRA) to Hartmann's procedure (HP) for Hinchey III/IV diverticulitis. METHODS: A systematic literature search was conducted to identify observational studies and randomised control trials (RCTs) of patients with Hinchey III/IV diverticulitis undergoing sigmoidectomy that compared PRA to HP. The methodological quality of the included studies was assessed systematically (Newcastle-Ottawa, Jadad and Cochrane risk of bias scores) and a meta-analysis was performed. RESULTS: After removal of duplicates, 12 studies including 4 RCTs were identified. The analysis included 918 patients, of whom 367 (39.98%) underwent PRA. Both the initial stoma rate (risk ratio [RR] persistent stoma 0.43, 95% confidence interval [CI] 0.26, 0.71, p = 0.001; I2 = 99%, p < 0.0001) and the rate of permanent stoma after combining the first (emergency surgery) and second (stoma reversal) procedures were lower in the PRA group. There was no difference in in 30-day mortality; however, PRA resulted in a reduction in overall mortality as well as major complications after the initial operation (RR 0.67, 95% CI 0.46, 0.97, p = 0.03; I2 = 22%, p = 0.26), stoma reversal (RR 0.48, 95% CI 0.26, 0.92, p = 0.03; I2 = 0%, p = 0.58) and when combining both procedures (RR 0.67, 95% CI 0.51, 0.88, p = 0.005; I2 = 0%, heterogeneity p = 0.58). A subgroup analysis of stoma reversal rates using data from only RCTs were consistent (RR permanent stoma, 0.33, 95% CI 0.13, 0.85, p = 0.02; I2 = 77%, p = 0.004) with the findings of the overall analysis. CONCLUSIONS: This meta-analysis demonstrates that PRA used in the management of haemodynamically stable patients with Hinchey grade III/IV diverticulitis leads to a lower overall persistent stoma rate, with reduced morbidity compared with the traditional management.