Search

Aims: Cancer staging is routinely done in a multidisciplinary team meeting (MDM). There is however no established quality assurance (QA) for MDM-recorded cancer staging. Conversely, radiotherapy peer review is a recommended QA process. This study aimed to compare the cancer staging of the multiprofessional radiotherapy peer review (with radiologists) against the referring MDMs., Materials and Methods: All head and neck intensity-modulated radiotherapy (IMRT) cases discussed in peer review between May 2023 to April 2024 were prospectively evaluated. Any radiological disease progression (PD) on IMRT-planning scan since the diagnostic scans, and patients' cancer staging, were prospectively recorded. These were compared with the MDM-recorded outcomes data., Results: A total of 235 IMRT cases were peer-reviewed: 166 definitive, 63 post-operative and 6 palliatives. Of the analysable definitive cases, 44/150 (29%) were found to have PD, with a mean interval from diagnostic to IMRT-planning scan of 51 days (Standard Deviation SD = 25), compared to 38 days (SD = 21) in the cohort without PD (p < 0.01). After the exclusion of 28 patients with the most advanced non-metastatic stage, 35 (30%) were upstaged with a mean interval from diagnostic to IMRT-planning of 49 days (SD = 26), compared to 39 days (SD = 23) in the cohort without upstage (p = 0.05). Twenty (57%) upstaged patients had evidence of PD, while the other 15 (43%) were upstaged despite the absence of PD. Two MDM-recorded T3-category larynx cancers were subsequently recommended for a primary laryngectomy due to T4a-category at peer review, and both were proven T4a pathologically. Three upstaged patients were recommended concomitant chemotherapy. The peer review recommended IMRT volume changes to 156 (66%) patients., Conclusion: Discrepancies in MDM staging can occur, and a protracted diagnosis and treatment pathway too can affect final cancer staging. Routine radiologist input in peer review can provide crucial post-MDM outcome assurance and the recommended clinical management., Competing Interests: Conflict of Interest The authors declare no conflict of interest., (Crown Copyright © 2024. Published by Elsevier Ltd. All rights reserved.)

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., Competing Interests: Declaration of Competing Interest None., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Background: The aim of this meta-analysis was to assess the impact of operative blood loss on short and long-term outcomes following colorectal cancer surgery., Methods: A systematic literature review and meta-analysis were performed, from inception to the 10th of August 2020. A comprehensive literature search was performed on the 10th of August 2020 of PubMed MEDLINE, Embase, Science Citation Index Expanded, and Cochrane Central Register of Controlled Trials. Only studies reporting on operative blood loss and postoperative short term or long-term outcomes in colorectal cancer surgery were considered for inclusion., Results: Forty-three studies were included, reporting on 59,813 patients. Increased operative blood loss was associated with higher morbidity, for blood loss greater than 150-350 ml (odds ratio [OR] 2.09, p < 0.001) and > 500 ml (OR 2.29, p = 0.007). Anastomotic leak occurred more frequently for blood loss above a range of 50-100 ml (OR 1.14, p = 0.007), 250-300 ml (OR 2.06, p < 0.001), and 400-500 ml (OR 3.15, p < 0.001). Postoperative ileus rate was higher for blood loss > 100-200 ml (OR 1.90, p = 0.02). Surgical site infections were more frequent above 200-500 ml (OR 1.96, p = 0.04). Hospital stay was increased for blood loss > 150-200 ml (OR 1.63, p = 0.04). Operative blood loss was significantly higher in patients that suffered morbidity (mean difference [MD] 133.16 ml, p < 0.001) or anastomotic leak (MD 69.56 ml, p = 0.02). In the long term, increased operative blood loss was associated with worse overall survival above a range of 200-500 ml (hazard ratio [HR] 1.15, p < 0.001), and worse recurrence-free survival above 200-400 ml (HR 1.33, p = 0.01). Increased blood loss was associated with small bowel obstruction caused by colorectal cancer recurrence for blood loss higher than 400 ml (HR 1.97, p = 0.03) and 800 ml (HR 3.78, p = 0.02)., Conclusions: Increased operative blood loss may adversely impact short term and long-term postoperative outcomes. Measures should be taken to minimize operative blood loss during colorectal cancer surgery. Due to the uncertainty of evidence identified, further research, with standardised methodology, is required on this important subject., (© 2022. Springer Nature Switzerland AG.)

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 &lt;18.5 had significantly worse overall survival [hazard ratio (HR) 1.91; P &lt; 0.0001], cancer-specific survival (HR = 1.91; P &lt; 0.0001), disease-free survival (HR = 1.50; P &lt; 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 &gt;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 &gt;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 &lt; 18.5) or class II/III obese (BMI &gt; 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., Competing Interests: Conflict of interest statement The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Background: The aim of this study was to compare energy devices used for intraoperative hemostasis during colorectal surgery., Methods: A systematic literature review and Bayesian network meta-analysis performed. MEDLINE, EMBASE, Science Citation Index Expanded, and Cochrane were searched from inception to August 11th 2021. Intraoperative outcomes were operative blood loss, operative time, conversion to open, conversion to another energy source. Postoperative outcomes were mortality, overall complications, minor complications and major complications, wound complications, postoperative ileus, anastomotic leak, time to first defecation, day 1 and 3 drainage volume, duration of hospital stay., Results: Seven randomized controlled trials (RCTs) were included, reporting on 680 participants, comparing conventional hemostasis, LigaSure™, Thunderbeat ® and Harmonic ® . Harmonic ® had fewer overall complications compared to conventional hemostasis. Operative blood loss was less with LigaSure™ (mean difference [MD] = 24.1 ml; 95% confidence interval [CI] - 46.54 to - 1.58 ml) or Harmonic ® (MD = 24.6 ml; 95% CI - 42.4 to - 6.7 ml) compared to conventional techniques. Conventional hemostasis ranked worst for operative blood loss with high probability (p = 0.98). LigaSure™, Harmonic ® or Thunderbeat ® resulted in a significantly shorter mean operative time by 42.8 min (95% CI - 53.9 to - 31.5 min), 28.3 min (95% CI - 33.6 to - 22.6 min) and 26.1 min (95% CI - 46 to - 6 min), respectively compared to conventional electrosurgery. LigaSure™ resulted in a significantly shorter mean operative time than Harmonic ® by 14.5 min (95% CI 1.9-27 min) and ranked first for operative time with high probability (p = 0.97). LigaSure™ and Harmonic ® resulted in a significantly shorter mean duration of hospital stay compared to conventional electrosurgery of 1.3 days (95% CI - 2.2 to - 0.4) and 0.5 days (95% CI - 1 to - 0.1), respectively. LigaSure™ ranked as best for hospital stay with high probability (p = 0.97). Conventional hemostasis was associated with more wound complications than Harmonic ® (odds ratio [OR] = 0.27; CI 0.08-0.92). Harmonic ® ranked best with highest probability (p = 0.99) for wound complications. No significant differences between energy devices were identified for the remaining outcomes., Conclusions: LigaSure™, Thunderbeat ® and Harmonic ® may be advantageous for reducing operative blood loss, operative time, overall complications, wound complications, and duration of hospital stay compared to conventional techniques. The energy devices result in comparable perioperative outcomes and no device is superior overall. However, included RCTs were limited in number and size, and data were not available to compare all energy devices for all outcomes of interest., (© 2022. Springer Nature Switzerland AG.)

Aim: The aim was to assess the benefit of adjuvant chemotherapy in high-risk Stage II colorectal cancer., Method: A systematic literature review and meta-analysis was performed comparing survival in patients with resected Stage II colorectal cancer and high-risk features having postoperative chemotherapy vs no chemotherapy., Results: Of 1031 articles screened, 29 were included, reporting on 183 749 participants. Adjuvant chemotherapy significantly improved overall survival [hazard ratio (HR) 0.61, P < 0.0001], disease-specific survival (HR = 0.73, P = 0.05) and disease-free survival (HR = 0.59, P < 0.0001) compared to no chemotherapy. Adjuvant chemotherapy significantly increased 5-year overall survival (OR = 0.53, P = 0.0008) and 5-year disease-free survival (OR = 0.50, P = 0.001). Overall survival and disease-free survival remained significantly prolonged during subgroup analysis of studies published from 2015 onwards (HR = 0.60, P < 0.0001; HR = 0.65, P = 0.0001; respectively), in patients with two or more high-risk features (HR = 0.59, P = 0.0001; HR = 0.70, P = 0.03; respectively) and in colon cancer (HR = 0.61, P < 0.0001; HR = 0.51, P = 0.0001; respectively). Overall survival, disease-specific survival and disease-free survival during subgroup analysis of individual high-risk features were T4 tumour (HR = 0.58, P < 0.0001; HR = 0.50, P = 0.003; HR = 0.75, P = 0.05), < 12 lymph nodes harvested (HR = 0.67, P = 0.0002; HR = 0.80, P = 0.17; HR = 0.72, P = 0.02), poor differentiation (HR = 0.84, P = 0.35; HR = 0.85, P = 0.23; HR = 0.61, P = 0.41), lymphovascular or perineural invasion (HR = 0.55, P = 0.05; HR = 0.59, P = 0.11; HR = 0.76, P = 0.05) and emergency surgery (HR = 0.60, P = 0.02; HR = 0.68, P = 0.19)., Conclusion: Adjuvant chemotherapy in high-risk Stage II colorectal cancer results in a modest survival improvement and should be considered on an individual patient basis. Due to potential heterogeneity and selection bias of the included studies, and lack of separate rectal cancer data, further large randomized trials with predefined inclusion criteria and standardized chemotherapy regimens are required., (Colorectal Disease © 2020 The Association of Coloproctology of Great Britain and Ireland.)

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.

Aim: There is no consensus as to which ileoanal pouch design provides better outcomes after restorative proctocolectomy. This study compares different pouch designs., Method: A systematic review of the literature was performed. A random effects meta-analytical model was used to compare adverse events and functional outcome., Results: Thirty comparative studies comparing J, W, S and K pouch designs were included. No significant differences were identified between the different pouch designs with regard to anastomotic dehiscence, anastomotic stricture, pelvic sepsis, wound infection, pouch fistula, pouch ischaemia, perioperative haemorrhage, small bowel obstruction, pouchitis and sexual dysfunction. The W and K designs resulted in fewer cases of pouch failure compared with the J and S designs. J pouch construction resulted in a smaller maximum pouch volume compared with W and K pouches. Stool frequency per 24 h and during daytime was higher following a J pouch than W, S or K constructions. The J design resulted in increased faecal urgency and seepage during daytime compared with the K design. The use of protective pads during daytime and night-time was greater with a J pouch compared to S or K. The use of antidiarrhoeal medication was greater after a J reservoir than a W reservoir. Difficulty in pouch evacuation requiring intubation was higher with an S pouch than with W or J pouches., Conclusion: Despite its ease of construction and comparable complication rates, the J pouch is associated with higher pouch failure rates and worse function. Patient characteristics, technical factors and surgical expertise should be considered when choosing pouch design., (Colorectal Disease © 2018 The Association of Coloproctology of Great Britain and Ireland.)

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., (Copyright © 2016 Elsevier Inc. All rights reserved.)

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., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.)

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.