Systematic review and meta-analysis of survival outcomes in T2a and T2b gallbladder cancers.

BACKGROUND: The 8th edition of AJCC TNM staging of Gallbladder cancer subdivided T2 stage into T2a and T2b based on tumour location. This meta-analysis aimed to investigate the long-term outcomes in T2a and T2b gallbladder cancers. METHODS: Literature search of Medline, Web of science, Embase and Cochrane databases was performed. Study characteristics, survival and recurrence data were extracted for meta-analysis of effect estimates and of individual patient data. RESULTS: Fifteen retrospective studies (2531 patients, T2a = 1332, T2b = 199) were included in the meta-analysis. Overall survival (OS) was significantly worse in patients with T2b compared to T2a tumours (HR 2.18, 95% CI 1.67-2.86, p < 0.0001). Meta-analysis of individual patient data (n = 629) showed similar results (HR 1.92, 95% CI 1.43-2.58, p < 0.00001). Patients with T2b tumours had higher risk of recurrence compared to T2a (OR 3.19, 95% CI 1.40-7.28, p = 0.006) and were more likely to receive adjuvant chemotherapy (OR 1.76, 95% CI 1.12-2.84, p = 0.014). Liver resection improved OS in T2b tumours (HR 2.99, CI 1.73-5.16, p < 0.0001). CONCLUSION: T2b gallbladder tumours have worse overall survival and increase risk of recurrence compared to T2a. Liver resection appears to improve OS in patients with T2b tumours. However, high quality multicenter data is required to confirm these results.

Effect of anastomotic leaks on long-term survival after oesophagectomy for oesophageal cancer: systematic review and meta-analysis.

INTRODUCTION: Long-term survival after curative surgery for oesophageal cancer surgery remains poor, and the prognostic impact of anastomotic leak (AL) remains unknown. A meta-analysis was conducted to investigate the impact of AL on long-term survival. METHODS: A systematic electronic search for articles was performed for studies published between 2001 and 2020 evaluating the long-term oncological impact of AL. Meta-analysis was performed using the DerSimonian-Laird random-effects model to compute hazard ratios and 95% confidence intervals. RESULTS: Nineteen studies met the inclusion criteria, yielding a total of 9885 patients. Long-term survival was significantly reduced after AL (HR: 1.79, 95% CI: 1.33-2.43). AL was associated with significantly reduced overall survival in studies within hospital volume Quintile 1 (HR: 1.35, 95% CI: 1.12-1.63) and Quintile 2 (HR: 1.83, 95% CI: 1.35-2.47). However, no significant association was found for studies within Quintile 3 (HR: 2.24, 95% CI: 0.85-5.88), Quintile 4 (HR: 2.59, 95% CI: 0.67-10.07), and Quintile 5 (HR: 1.29, 95% CI: 0.92-1.81). AL was significantly associated with poor long-term survival in patients with associated overall Clavien Dindo Grades 1-5 (HR: 2.17, 95% CI: 1.31-3.59) and severe Clavien Dindo Grades 3-5 (HR: 1.42, 95% CI: 1.14-1.78) complications. CONCLUSIONS: AL has a negative prognostic impact on long-term survival after restorative resection of oesophageal cancers, particularly in low-volume centers. Future efforts must be focused on strategies to minimize the septic and immunological response to AL with early recognition and treatment thus reducing the impact on long-term survival.

Long-term survival after minimally invasive resection versus open pancreaticoduodenectomy for periampullary cancers: a systematic review, meta-analysis and meta-regression.

BACKGROUND: It remains unclear whether minimally invasive pancreaticoduodenectomy (MIPD) and open pancreaticoduodenectomy (OPD) influences long-term survival in periampullary cancers. This review aims evaluate long-term survival between MIPD and OPD for periampullary cancers. METHODS: A systematic review was performed to identify studies comparing long-term survival after MIPD and OPD. The I2 test was used to test for statistical heterogeneity and publication bias using Egger test. Random-effects meta-analysis was performed for all-cause 5-year (main outcome) and 3-year survival, and disease-specific 5-year and 3-year survival. Meta-regression was performed for the 5-year and 3-year survival outcomes with adjustment for study (region, design, case matching), hospital (centre volume), patient (ASA grade, gender, age), and tumor (stage, neoadjuvant therapy, subtype (i.e. ampullary, distal bile duct, duodenal, pancreatic)). Sensitivity analyses performed on studies including pancreatic ductal adenocarcinoma (PDAC) only. RESULTS: The review identified 31 relevant studies. Among all 58,622 patients, 8716 (14.9%) underwent MIPD and 49,875 (85.1%) underwent OPD. Pooled analysis revealed similar 5-year overall survival after MIPD compared with OPD (HR: 0.78, 95% CI 0.50-1.22, p = 0.2). Meta-regression indicated case matching, and ASA Grade II and III as confounding covariates. The statistical heterogeneity was limited (I2 = 12, χ2 = 0.26) and the funnel plot was symmetrical both according to visual and statistical testing (Egger test = 0.32). Sensitivity subset analyses for PDAC demonstrated similar 5-year overall survival after MIPD compared with OPD (HR 0.69, 95% CI: 0.32-1.50, p = 0.3). CONCLUSION: Long-term survival after MIPD is non-inferior to OPD. Thus, MIPD can be recommended as a standard surgical approach for periampullary cancers.

Does minimally invasive liver resection improve long-term survival compared to open resection for hepatocellular carcinoma? A systematic review and meta-analysis.

INTRODUCTION: Minimally invasive liver surgery for hepatocellular carcinoma has gained widespread interest as an alternative to conventional open liver surgery. However, long-term survival benefits of this approach seem unclear. This meta-analysis was conducted to investigate long-term survival following minimally invasive liver surgery. METHOD: A systematic review was performed to identify studies comparing long-term survival after minimally invasive liver surgery and open liver surgery until January 2020. The I2 test was used to test for statistical heterogeneity and publication bias was assessed using Egger test. Random-effects meta-analysis was performed for all-cause 5-year (main outcome) and 3-year mortality, and disease-specific 5-year and 3-year mortality. Meta-regression was performed for the 5-year and 3-year survival outcomes with adjustment for study factors (region, design), annual center volume, patient factors (American Society of Anesthesiologists (ASA) grade, gender, age, body mass index, cirrhosis, tumor size, and number), and resection extent. Sensitivity analyses were performed on studies by study year, region, annual center volume, and resection type. RESULT: The review identified 50 relevant studies including 13,731 patients undergoing liver resection for hepatocellular carcinoma of which 4071 (25.8%) underwent minimally invasive liver surgery. Pooled analysis revealed similar all-cause (odds ratio: 0.83, 95% confidence interval: 0.70-1.11, p = 0.3) and disease-specific (odds ratio: 0.93, 95% confidence interval: 0.80-1.09, p = 0.4) 5-year mortality after minimally invasive liver surgery compared with open liver surgery. Sensitivity analysis of published studies from 2010 to 2019 demonstrated a significantly lower disease-specific 3-year mortality (odds ratio: 0.75, 95% confidence interval: 0.59-0.96, p = 0.022) and all-cause 5-year mortality (odds ratio: 0.63, 95% confidence interval: 0.50-0.81, p = 0.002). Meta-regression identified no confounding factors in all analyses. CONCLUSIONS: Improvement in minimally invasive liver surgery techniques over the past decade appears to demonstrate superior disease-specific mortality with minimally invasive liver surgery compared to open liver surgery. Therefore, minimally invasive liver surgery can be recommended as an alternative surgical approach for hepatocellular carcinoma.

Clinical utility of clonal origin determination in managing recurrent hepatocellular carcinoma.

INTRODUCTION: Recurrence is the driving factor for reduced long-term survival in patients following resected hepatocellular carcinoma (HCC). Extensive research efforts have been conducted to understand the molecular processes precipitating disease recurrence. Modern genomic techniques have identified two distinct mechanisms for recurrent HCC (RHCC): Intrahepatic metastasis (IM-HCC); and multicentric origin (MO-HCC). Medline, EMBASE and Cochrane library were methodically searched for primary research articles in English with the aim of appraising existing literature on the identification of clonal origin of RHCC and its potential clinical utility. AREAS COVERED: Molecular and next-generation sequencing techniques, when applied to clonal origin identification, yield superior accuracy than traditional clinicopathological criteria. Despite various treatment modalities, no optimal therapy has yet been identified for treating clonally differentiated RHCC. Patients with MO-HCC appear to experience improved long-term survival following re-treatment compared to their IM-HCC counterparts (91.7% vs 22.9% 5-year survival, p < 0.001). However, cautious interpretation is advised as heterogeneous classification criteria and small sample sizes restrict the generalizability of such findings. EXPERT OPINION: Improved identification of clonal origin in RHCC may facilitate further research on RHCC treatment strategies and enable the development of novel therapeutic targets, potentially leading to individualized treatment approaches in the future.

Elderly patients have increased perioperative morbidity and mortality from oesophagectomy for oesophageal cancer: A systematic review and meta-analysis.

BACKGROUND: Although oesophagectomy remains technically challenging and associated with high morbidity and mortality, it is now increasingly performed in an ever-ageing population with improvement in perioperative care. However, the risks in the elderly population are poorly quantified. The study aims to review the current evidence to quantify further the postoperative risk of oesophagectomy for cancer in the elderly population compared to younger patients. METHOD: A systematic literature search of PubMed, EMBASE and the Cochrane Library databases was conducted including studies reporting oesophagectomy for cancer in the elderly population. A meta-analysis was reported in accordance with the recommendations of the Cochrane Library and PRISMA guidelines. Primary outcome was overall complications and secondary outcomes were pulmonary and cardiac complications, anastomotic leaks, overall and disease-free survival. RESULTS: This review identified 37 studies incorporating 30,836 patients. Increasing age was significantly associated with increased rates of overall complications (OR 1.67, CI95%: 1.42-1.96), pulmonary complications (OR 1.87, CI95%: 1.48-2.35), and cardiac complications (OR: 2.22, CI95%: 1.95-2.53). However, there was no increased risk of anastomotic leak (OR: 0.98, CI95%: 0.85-1.18). Elderly patients were significantly more likely to have lower rates of 5-year overall survival (OR: 1.36, CI95%: 1.11-1.66) and 5-year disease-free survival (OR: 1.72, CI95%: 1.51-1.96). CONCLUSION: Elderly patients undergoing oesophagectomy for cancer are at increased risk of overall, pulmonary and cardiac complications, irrespective of age subgroups, albeit no difference in anastomotic leaks. Therefore, they represent high-risk patients warranting implementation of preoperative pathways such as prehabilitation to improve cardiopulmonary fitness prior to surgery, although benefit of prehabilitation is yet to be proven. This information will also aid future pre-operative counselling and informed consent.

Elective Cancer Surgery in COVID-19-Free Surgical Pathways During the SARS-CoV-2 Pandemic: An International, Multicenter, Comparative Cohort Study.

PURPOSE: As cancer surgery restarts after the first COVID-19 wave, health care providers urgently require data to determine where elective surgery is best performed. This study aimed to determine whether COVID-19-free surgical pathways were associated with lower postoperative pulmonary complication rates compared with hospitals with no defined pathway. PATIENTS AND METHODS: This international, multicenter cohort study included patients who underwent elective surgery for 10 solid cancer types without preoperative suspicion of SARS-CoV-2. Participating hospitals included patients from local emergence of SARS-CoV-2 until April 19, 2020. At the time of surgery, hospitals were defined as having a COVID-19-free surgical pathway (complete segregation of the operating theater, critical care, and inpatient ward areas) or no defined pathway (incomplete or no segregation, areas shared with patients with COVID-19). The primary outcome was 30-day postoperative pulmonary complications (pneumonia, acute respiratory distress syndrome, unexpected ventilation). RESULTS: Of 9,171 patients from 447 hospitals in 55 countries, 2,481 were operated on in COVID-19-free surgical pathways. Patients who underwent surgery within COVID-19-free surgical pathways were younger with fewer comorbidities than those in hospitals with no defined pathway but with similar proportions of major surgery. After adjustment, pulmonary complication rates were lower with COVID-19-free surgical pathways (2.2% v 4.9%; adjusted odds ratio [aOR], 0.62; 95% CI, 0.44 to 0.86). This was consistent in sensitivity analyses for low-risk patients (American Society of Anesthesiologists grade 1/2), propensity score-matched models, and patients with negative SARS-CoV-2 preoperative tests. The postoperative SARS-CoV-2 infection rate was also lower in COVID-19-free surgical pathways (2.1% v 3.6%; aOR, 0.53; 95% CI, 0.36 to 0.76). CONCLUSION: Within available resources, dedicated COVID-19-free surgical pathways should be established to provide safe elective cancer surgery during current and before future SARS-CoV-2 outbreaks.