A systematic review and network meta-analysis of randomised controlled trials comparing neoadjuvant treatment strategies for stage II and III rectal cancer.

AIM: Multiple neoadjuvant therapy strategies have been used and compared for rectal cancer and there has been no true consensus as to the optimal neoadjuvant therapy regimen. The aim is to identify and compare the neoadjuvant therapies available for stage II and III rectal cancer. DESIGN: A systematic literature review was performed, from inception to August 2022, of the following databases: MEDLINE, EMBASE, Science Citation Index Expanded, Cochrane Library. Only randomized controlled trials comparing neoadjuvant therapies for stage II and III rectal cancer were considered. Stata was used to draw network plots, and a Bayesian network meta-analysis was conducted through models utilizing the Markov Chain Monte Carlo method in WinBUGS. RESULTS: A total of 58 articles were included based on 41 randomised controlled trials, reporting on 12,404 participants that underwent 15 neoadjuvant treatment regimens. No significant difference was identified between treatments for major or total postoperative complications, anastomotic leak rates, or sphincter-saving surgery. Straight to surgery (STS) ranked as best treatment for preoperative toxicity but ranked worst treatment for positive resection margins and complete response. STS had significantly increased positive resection margins compared to long-course chemoradiotherapy with short-wait (LCCRT-SW) or long-wait (LCCRT-LW) to surgery, or short-course radiotherapy with short-wait (SCRT-SW) or immediate surgery (SCRT-IS). LCCRT-SW or LCCRT-LW resulted in significantly increased complete response rates compared to STS. LCCRT-LW significantly improved 2-year overall survival compared to STS, SCRT-IS, SCRT-SW. Total neoadjuvant therapy regimes with short-course radiotherapy followed by consolidation chemotherapy (SCRT-CT-SW), induction chemotherapy followed by long-course chemoradiotherapy (CT-LCCRT-S), long-course chemoradiotherapy followed by consolidation chemotherapy (LCCRT-CT-S), significantly improved positive resection margins, complete response, and disease-free survival compared to STS. Chemotherapy with monoclonal antibodies followed by long-course chemoradiotherapy (CT+MAB-LCCRT+MAB-S) significantly improved complete response and positive resection margins compared to STS, and 2-year disease-free survival compared to STS, SCRT-IS, SCRT-SW, SCRT-CT-SW, LCCRT-SW, LCCRT-LW. CT+MAB-LCCRT+MAB-S ranked as best treatment for disease-free survival and overall survival. CONCLUSIONS: Conventional neoadjuvant therapies with short-course radiation or long-course chemoradiotherapy have oncological benefits compared to no neoadjuvant therapy without increasing perioperative complication rates. Prolonged wait to surgery may improve oncological outcomes. Total neoadjuvant therapies provide additional benefits in terms of complete response, positive resection margins, and disease-free survival. Monoclonal antibody therapy may further improve oncological outcomes but currently is only applicable to a small subgroup of patients and requires further validation.

A systematic review and meta-analysis assessing the impact of body mass index on long-term survival outcomes after surgery for colorectal cancer.

BACKGROUND: The impact of body mass index (BMI) on long-term survival outcomes after colorectal cancer surgery is debated. DESIGN: A systematic literature review and meta-analysis was performed to compare long-term survival outcomes of patients of different BMI categories after colorectal cancer surgery. RESULTS: Of the 2588 articles screened, 56 articles met the inclusion criteria, reporting on 72,582 participants. Patients with BMI <18.5 had significantly worse overall survival [hazard ratio (HR) 1.91; P < 0.0001], cancer-specific survival (HR = 1.91; P < 0.0001), disease-free survival (HR = 1.50; P < 0.0001) and recurrence-free survival (HR = 1.13; P = 0.007) compared to patients with a BMI of 18.5-25. There was no significant difference between those with BMI 25-30 and 18.5-25 in overall survival, cancer-specific survival, disease-free survival and recurrence-free survival, except for the subgroup of patients with colon cancer where patients with BMI 25-30 had significantly improved overall survival (HR = 0.90; P = 0.05) and disease-free survival (HR = 0.90; P = 0.04). Patients with BMI >30 had significantly worse disease-free survival (HR = 1.05; P = 0.03) compared to patients with a BMI of 18.5-25, but no significant difference in overall survival, cancer-specific survival and recurrence-free survival. Patients with BMI >35 compared to 18.5-25 had significantly worse overall survival (HR = 1.24; P = 0.02), cancer-specific survival (HR = 1.36; P = 0.01), disease-free survival (HR = 1.15; P = 0.03) and recurrence-free survival for colon (HR = 1.11; P = 0.04) and rectal (HR = 4.10; P = 0.04) cancer. CONCLUSIONS: Being underweight (BMI < 18.5) or class II/III obese (BMI > 35) at the time of colorectal cancer surgery may result in worse long-term survival outcomes, whereas being overweight (BMI 25-30) may improve survival in a subgroup of patients with colon cancer. Optimising BMI may preoperatively improve long-term survival after surgery for colorectal cancer.

Primary Tumor Resection in Patients with Incurable Localized or Metastatic Colorectal Cancer: A Systematic Review and Meta-analysis.

BACKGROUND: To assess the impact of primary tumor resection (PTR) on survival and morbidity in incurable colorectal cancer. METHODS: Systematic literature review and meta-analysis to compare PTR versus primary tumor intact (PTI). RESULTS: Seventy-seven studies were included, reporting on 159,991 participants (94,745 PTR; 65,246 PTI). PTR improved overall survival (hazard ratio [HR] 0.59, P < 0.0001; mean difference [MD] 7.27 months, P < 0.0001), cancer-specific survival (HR 0.47, MD 10.80), and progression-free survival (HR 0.76, MD 1.67). Overall survival remained significantly improved during subgroup analysis of asymptomatic patients (HR 0.69, MD 3.86), elderly patients (HR 0.46, MD 7.71), patients diagnosed after 2000 (HR 0.62, MD 7.29), patients with colon (HR 0.58, MD 6.31) or rectal (HR 0.54, MD 6.88) primary tumor, patients undergoing resection of primary tumor versus non-resectional surgery (NRS) to treat primary tumor complications (HR 0.56, MD 8.72), and of studies with propensity score analysis (HR 0.65, MD 5.68). Overall survival per treatment strategy was: [PTI/chemotherapy] 14.30 months, [PTI/bevacizumab] 17.27 months, [PTR/chemotherapy] 21.52 months, [PTR/bevacizumab] 27.52 months. PTR resulted in 4.5% perioperative mortality and 22.4% morbidity (major adverse events 10.2%, minor 18.5%, reoperation 2.5%, intraabdominal collection/sepsis 2.2%). PTI had 21.7% morbidity (obstruction 14.4%, anemia 11.0%, hemorrhage 1.5%, perforation 0.6%, adverse events requiring surgery 15.8%). NRS resulted in 10.6% perioperative mortality and 21.7% morbidity (major 7.9%, minor 21.7%, reoperation 0.1%). CONCLUSIONS: PTR in patients with incurable colorectal cancer results in a limited improvement of survival without a significant increase in morbidity. PTR should be considered by the multidisciplinary team on an individual patient basis.

Hydrolysed formula and risk of allergic or autoimmune disease: systematic review and meta-analysis.

OBJECTIVE: To determine whether feeding infants with hydrolysed formula reduces their risk of allergic or autoimmune disease. DESIGN: Systematic review and meta-analysis, as part of a series of systematic reviews commissioned by the UK Food Standards Agency to inform guidelines on infant feeding. Two authors selected studies by consensus, independently extracted data, and assessed the quality of included studies using the Cochrane risk of bias tool. DATA SOURCES: Medline, Embase, Web of Science, CENTRAL, and LILACS searched between January 1946 and April 2015. ELIGIBILITY CRITERIA FOR SELECTING STUDIES: Prospective intervention trials of hydrolysed cows' milk formula compared with another hydrolysed formula, human breast milk, or a standard cows' milk formula, which reported on allergic or autoimmune disease or allergic sensitisation. RESULTS: 37 eligible intervention trials of hydrolysed formula were identified, including over 19,000 participants. There was evidence of conflict of interest and high or unclear risk of bias in most studies of allergic outcomes and evidence of publication bias for studies of eczema and wheeze. Overall there was no consistent evidence that partially or extensively hydrolysed formulas reduce risk of allergic or autoimmune outcomes in infants at high pre-existing risk of these outcomes. Odds ratios for eczema at age 0-4, compared with standard cows' milk formula, were 0.84 (95% confidence interval 0.67 to 1.07; I(2)=30%) for partially hydrolysed formula; 0.55 (0.28 to 1.09; I(2)=74%) for extensively hydrolysed casein based formula; and 1.12 (0.88 to 1.42; I(2)=0%) for extensively hydrolysed whey based formula. There was no evidence to support the health claim approved by the US Food and Drug Administration that a partially hydrolysed formula could reduce the risk of eczema nor the conclusion of the Cochrane review that hydrolysed formula could allergy to cows' milk. CONCLUSION: These findings do not support current guidelines that recommend the use of hydrolysed formula to prevent allergic disease in high risk infants. REVIEW REGISTRATION: PROSPERO CRD42013004252.

A network meta-analysis comparing perioperative outcomes of interventions aiming to decrease ischemia reperfusion injury during elective liver resection.

OBJECTIVE: This study sought to compare the perioperative outcomes of interventions aiming to decrease ischemia-reperfusion (IR) injury during elective liver resection. METHOD: A comprehensive literature search was performed to identify randomized controlled trials. A Bayesian network meta-analysis was performed using the Markov chain Monte Carlo method in WinBUGS following the guidelines of the National Institute for Health and Clinical Excellence Decision Support Unit. Odds ratios for binary outcomes and mean differences for continuous outcomes were calculated using a fixed effect model or a random effects model according to model fit. RESULTS: Forty-four trials with 2,457 patients having undergone liver resection were included and were divided into 8 classes of interventions aimed at decreasing IR injury and a control group, which was hepatectomy alone. There was no difference between the different interventions in mortality, quantity of blood transfusion, and durations of stay in an intensive therapy unit between any pairwise comparisons. Patients treated with ischemic preconditioning, cardiovascular modulators, and miscellaneous interventions had significantly fewer serious adverse events compared with patients undergoing liver resection alone. Ischemic preconditioning patients had significantly fewer transfusion proportions and shorter operative time than patients treated with steroids. Ischemic preconditioning had significantly less operative blood loss compared with all other interventions, and a lesser duration of hospital stay than hepatectomy alone. Sensitivity analysis showed that the drugs sevoflurane (a volatile anesthetic), verapamil (a calcium channel blocker), and gabexate mesilate (a thrombin inhibitor) produced fewer serious adverse events compared with hepatectomy alone. CONCLUSION: Ischemic preconditioning resulted in multiple beneficial clinical endpoints and further RCTs seem to be needed to confirm its clinical benefits.

Proteomic biomarkers of type 2 diabetes mellitus risk in women with polycystic ovary syndrome.

Women with polycystic ovary syndrome (PCOS) are at increased risk of developing insulin resistance and type 2 diabetes mellitus (T2DM). In this study, we attempted to list the proteomic biomarkers of PCOS and T2DM that have been published in the literature so far. We identified eight common biomarkers that were differentially expressed in both women with PCOS and T2DM when compared with healthy controls. These include pyruvate kinase M1/M2, apolipoprotein A-I, albumin, peroxiredoxin 2, annexin A2, α-1-B-glycoprotein, flotillin-1 and haptoglobin. These biomarkers could help improve our understanding of the links between PCOS and T2DM and could be potentially used to identify subgroups of women with PCOS at increased risk of T2DM. More studies are required to further evaluate the role these biomarkers play in women with PCOS and T2DM.