Ferric carboxymaltose infusion versus oral iron supplementation for preoperative iron deficiency anaemia in patients with colorectal cancer (FIT):a multicentre, open-label, randomised, controlled trial

Background: A third of patients with colorectal cancer who are eligible for surgery in high-income countries have concomitant anaemia associated with adverse outcomes. We aimed to compare the efficacy of preoperative intravenous and oral iron supplementation in patients with colorectal cancer and iron deficiency anaemia. Methods: In the FIT multicentre, open-label, randomised, controlled trial, adult patients (aged 18 years or older) with M0 stage colorectal cancer scheduled for elective curative resection and iron deficiency anaemia (defined as haemoglobin level of less than 7·5 mmol/L (12 g/dL) for women and less than 8 mmol/L (13 g/dL) for men, and a transferrin saturation of less than 20%) were randomly assigned to either 1–2 g of ferric carboxymaltose intravenously or three tablets of 200 mg of oral ferrous fumarate daily. The primary endpoint was the proportion of patients with normalised haemoglobin levels before surgery (≥12 g/dL for women and ≥13 g/dL for men). An intention-to-treat analysis was done for the primary analysis. Safety was analysed in all patients who received treatment. The trial was registered at ClincalTrials.gov, NCT02243735, and has completed recruitment. Findings: Between Oct 31, 2014, and Feb 23, 2021, 202 patients were included and assigned to intravenous (n=96) or oral (n=106) iron treatment. Treatment began a median of 14 days (IQR 11–22) before surgery for intravenous iron and 19 days (IQR 13–27) for oral iron. Normalisation of haemoglobin at day of admission was reached in 14 (17%) of 84 patients treated intravenously and 15 (16%) of 97 patients treated orally (relative risk [RR] 1·08 [95% CI 0·55–2·10]; p=0·83), but the proportion of patients with normalised haemoglobin significantly increased for the intravenous treatment group at later timepoints (49 [60%] of 82 vs 18 [21%] of 88 at 30 days; RR 2·92 [95% CI 1·87–4·58]; p&lt;0·0001). The most prevalent treatment-related adverse event was discoloured faeces (grade 1) after oral iron treatment (14 [13%] of 105), and no treatment-related serious adverse events or deaths were observed in either group. No differences in other safety outcomes were seen, and the most common serious adverse events were anastomotic leakage (11 [5%] of 202), aspiration pneumonia (5 [2%] of 202), and intra-abdominal abscess (5 [2%] 202). Interpretation: Normalisation of haemoglobin before surgery was infrequent with both treatment regimens, but significantly improved at all other timepoints following intravenous iron treatment. Restoration of iron stores was feasible only with intravenous iron. In selected patients, surgery might be delayed to augment the effect of intravenous iron on haemoglobin normalisation. Funding: Vifor Pharma.</p

Genome-Wide Association Study in BRCA1 Mutation Carriers Identifies Novel Loci Associated with Breast and Ovarian Cancer Risk

BRCA1-associated breast and ovarian cancer risks can be modified by common genetic variants. To identify further cancer risk-modifying loci, we performed a multi-stage GWAS of 11,705 BRCA1 carriers (of whom 5,920 were diagnosed with breast and 1,839 were diagnosed with ovarian cancer), with a further replication in an additional sample of 2,646 BRCA1 carriers. We identified a novel breast cancer risk modifier locus at 1q32 for BRCA1 carriers (rs2290854, P = 2.7×10-8, HR = 1.14, 95% CI: 1.09-1.20). In addition, we identified two novel ovarian cancer risk modifier loci: 17q21.31 (rs17631303, P = 1.4×10-8, HR = 1.27, 95% CI: 1.17-1.38) and 4q32.3 (rs4691139, P = 3.4×10-8, HR = 1.20, 95% CI: 1.17-1.38). The 4q32.3 locus was not associated with ovarian cancer risk in the general population or BRCA2 carriers, suggesting a BRCA1-specific associat

Preoperative Assessment of Obstructive Sleep Apnea in Bariatric Patients Using Polysomnography or Polygraphy

Background: Preoperative assessment of obstructive sleep apnea (OSA) in patients scheduled for bariatric surgery can be performed by in-laboratory polysomnography (PSG) or by portable polygraphy (PP) at home. We aimed to evaluate the association between PSG/PP, OSA diagnosis, and implementation of continuous positive airway pressure (CPAP) therapy. Methods: All patients who underwent bariatric surgery from 2015 to 2017 were retrospectively reviewed. Patients underwent preoperative PSG or PP, based on prevailing protocols or at the physician’s discretion. Logistic regression analyses were performed to determine predictors of CPAP implementation. OSA-related postoperative complications were analyzed in both groups. Results: During the study period, 1464 patients were included. OSA was diagnosed in 79% of 271 patients undergoing PSG, compared to 64% of 1193 patients undergoing PP (p < 0.001), with median apnea–hypopnea index (AHI) of 15.8 and 7.7, respectively. CPAP treatment was initiated in 52% and 27% of patients, respectively, p < 0.001. Predictors (with adjusted odds ratio) in multivariate regression analysis for CPAP implementation were as follows: male gender (5.15), BMI ≥ 50 (3.85), PSG test (2.74), hypertension (2.38), and age ≥ 50 (1.87). OSA-related complications did not differ between groups (p = 0.277). Conclusion: Both PSG and PP are feasible options for preoperative OSA assessment in bariatric patients. When PP is performed, some underdiagnosis may occur as cases of mild OSA may be missed. However, clinically relevant OSA is detected by both diagnostic tools. No difference in OSA-related complications was found. PP is a safe, less invasive option and can be considered as a suitable measure for OSA assessment in this population

Preoperative Assessment of Obstructive Sleep Apnea in Bariatric Patients Using Polysomnography or Polygraphy

Background: Preoperative assessment of obstructive sleep apnea (OSA) in patients scheduled for bariatric surgery can be performed by in-laboratory polysomnography (PSG) or by portable polygraphy (PP) at home. We aimed to evaluate the association between PSG/PP, OSA diagnosis, and implementation of continuous positive airway pressure (CPAP) therapy. Methods: All patients who underwent bariatric surgery from 2015 to 2017 were retrospectively reviewed. Patients underwent preoperative PSG or PP, based on prevailing protocols or at the physician’s discretion. Logistic regression analyses were performed to determine predictors of CPAP implementation. OSA-related postoperative complications were analyzed in both groups. Results: During the study period, 1464 patients were included. OSA was diagnosed in 79% of 271 patients undergoing PSG, compared to 64% of 1193 patients undergoing PP (p < 0.001), with median apnea–hypopnea index (AHI) of 15.8 and 7.7, respectively. CPAP treatment was initiated in 52% and 27% of patients, respectively, p < 0.001. Predictors (with adjusted odds ratio) in multivariate regression analysis for CPAP implementation were as follows: male gender (5.15), BMI ≥ 50 (3.85), PSG test (2.74), hypertension (2.38), and age ≥ 50 (1.87). OSA-related complications did not differ between groups (p = 0.277). Conclusion: Both PSG and PP are feasible options for preoperative OSA assessment in bariatric patients. When PP is performed, some underdiagnosis may occur as cases of mild OSA may be missed. However, clinically relevant OSA is detected by both diagnostic tools. No difference in OSA-related complications was found. PP is a safe, less invasive option and can be considered as a suitable measure for OSA assessment in this population

Incidence and characteristics of chronic and lymphoplasmacytic sclerosing pancreatitis in patients scheduled to undergo a pancreatoduodenectomy

AbstractBackgroundThe determination of the exact nature of a pancreatic head mass in a patient scheduled to undergo a pancreatoduodenectomy can be very difficult. This is important as patients who suffer from benign disease such as pancreatitis do not always require surgery. The aim of the present study was to analyse the incidence of pancreatitis and the signs and symptoms associated with these tumours mistaken for pancreatic cancer and the diagnostic procedures performed.MethodsA consecutive group of patients who underwent a pancreatoduodenectomy between 1992 and 2005 with histopathologically proven pancreatic adenocarcinoma (PCA) and pancreatitis were analysed.ResultsThe incidence of pancreatitis after pancreatoduodenectomy is 63 out of 639 patients who underwent a pancreaticoduodenectomy (9.9%). Of these patients, 24 patients (38%) had lymphoplasmacytic sclerosing pancreatitis (LPSP) and 31 patients (49%) had focal chronic pancreatitis. Eight patients (13%) had an intermediate form with characteristics of both. Pancreatic adenocarcinoma occurred in 227 patients (36%). The presence of pancreatitis without a discrete mass on endoscopic ultrasonography (EUS) seemed to have clinical relevance with a positive likelihood ratio of 5.1. Mortality after resection was nil in both groups.ConclusionThe incidence of pancreatitis is 9.9% for patients scheduled to undergo a pancreatoduodenectomy. Of these patients, 38% had LPSP, 13% had a intermediate form and 49% had focal chronic pancreatitis. The determination of the exact nature of a pancreatic head mass remains difficult

Protocol of a multicentre, prospective cohort study that evaluates cost-effectiveness of two perioperative care strategies for potential obstructive sleep apnoea in morbidly obese patients undergoing bariatric surgery

Introduction Despite the high prevalence of obstructive sleep apnoea (OSA) in obese patients undergoing bariatric surgery, OSA is undiagnosed in the majority of patients and thus untreated. While untreated OSA is associated with an increased risk of preoperative and postoperative complications, no evidence-based guidelines on perioperative care for these patients are available. The aim of the POPCORN study (Post-Operative Pulse oximetry without OSA sCreening vs perioperative continuous positive airway pressure (CPAP) treatment following OSA scReeNing by polygraphy (PG)) is to evaluate which perioperative strategy is the most cost-effective for obese patients undergoing bariatric surgery without a history of OSA. Methods and analysis In this multicentre observational cohort study, data from 1380 patients who will undergo bariatric surgery will be collected. Patients will receive either postoperative care with pulse oximetry monitoring and supplemental oxygen during the first postoperative night, or care that includes preoperative PG and CPAP treatment in case of moderate or severe OSA. Local protocols for perioperative care in each participating hospital will determine into which cohort a patient is placed. The primary outcome is cost-effectiveness, which will be calculated by comparing all healthcare costs with the quality-adjusted life-years (QALYs, calculated using EQ-5D questionnaires). Secondary outcomes are mortality, complications within 30 days after surgery, readmissions, reoperations, length of stay, weight loss, generic quality of life (QOL), OSA-specific QOL, OSA symptoms and CPAP adherence. Patients will receive questionnaires before surgery and 1, 3, 6 and 12 months after surgery to report QALYs and other patient-reported outcomes. Ethics and dissemination Approval from the Medical Research Ethics Committees United was granted in accordance with the Dutch law for Medical Research Involving Human Subjects Act (WMO) (reference number W17.050). Results will be submitted for publication in peer-reviewed journals and presented at (inter)national conferences. Trial registration number NTR6991. </p