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Richard ES, Hrycyshyn A, Salman N, Remtulla Tharani A, Abbruzzino A, Smith J, Kachura JJ, Sholzberg M, Mosko JD, Chadi SA, Burkes RL, Pankiw M, Brezden-Masley C. Iron Surveillance and Management in Gastro-Intestinal Oncology Patients: A National Physician Survey. Curr Oncol 2023; 30:9836-9848. [PMID: 37999134 PMCID: PMC10670404 DOI: 10.3390/curroncol30110714] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/27/2023] [Revised: 10/10/2023] [Accepted: 11/02/2023] [Indexed: 11/25/2023] Open
Abstract
PURPOSE Iron deficiency (ID) is a complication of gastrointestinal (GI) cancers that may manifest as iron deficiency anemia (IDA). Serum ferritin monitoring and oral iron supplementation have the limitations of being falsely elevated and poorly absorbed, respectively. This study aims to assess the discordance in surveillance, treatment practices, and awareness of ID/IDA in GI cancer patients by Canadian physicians treating these patients. METHODS From February 2020 to September 2021, a 22-question electronic survey was sent to medical oncologists (MOs), surgical oncologists (SOs), and gastroenterologists (GEs). The survey collected information about four domains: physician demographics, surveillance practices, treatment practices, and awareness of ID/IDA in GI cancer patients and ASCO/ASH guidelines. RESULTS A total of 108 (34 MOs, 19 SOs, and 55 GEs) of the 872 (12.4%) invited physicians completed the survey. Of these, 26.5% of MOs, 36.8% of SOs, and 70.9% of GEs measured baseline iron parameters, with few continuing surveillance throughout treatment. Ferritin was widely measured by MOs (88.9%), SOs (100%), and GEs (91.4%). Iron was supplemented if ID/IDA was identified pre-treatment by 66.7% of MOs, 85.7% of SOs, and 94.2% of GEs. Parenteral iron was prescribed by SOs (100%), while oral iron was prescribed by MOs (83.3%) and GEs (87.9%). Only 18.6% of physicians were aware of the ASCO/ASH guidelines regarding erythropoiesis-stimulating agents with parenteral iron for treating chemotherapy-induced anemia. CONCLUSION Results illustrate variations in practice patterns for IDA management across the different physician specialties. Moreover, there appeared to be gaps in the knowledge and care surrounding evidence-based IDA management principles which may contribute to poor clinical outcomes.
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Affiliation(s)
- Emilie S. Richard
- Department of Medicine, Mount Sinai Hospital, Sinai Health, Toronto, ON M5G 1X5, Canada
| | - Adriyan Hrycyshyn
- Department of Medicine, Mount Sinai Hospital, Sinai Health, Toronto, ON M5G 1X5, Canada
| | - Noor Salman
- Department of Medicine, Mount Sinai Hospital, Sinai Health, Toronto, ON M5G 1X5, Canada
| | | | - Alexandria Abbruzzino
- Department of Medicine, Mount Sinai Hospital, Sinai Health, Toronto, ON M5G 1X5, Canada
| | - Janet Smith
- Department of Medicine, Mount Sinai Hospital, Sinai Health, Toronto, ON M5G 1X5, Canada
| | - Jacob J. Kachura
- Department of Medicine, Mount Sinai Hospital, Sinai Health, Toronto, ON M5G 1X5, Canada
| | - Michelle Sholzberg
- Department of Medicine, Division of Oncology/Hematology, St. Michael’s Hospital, Unity Health Toronto, Toronto, ON M5B 1W8, Canada
- Department of Medicine, Temerty Faculty of Medicine, University of Toronto, Toronto, ON M5S 3H2, Canada
| | - Jeffrey D. Mosko
- Department of Medicine, Temerty Faculty of Medicine, University of Toronto, Toronto, ON M5S 3H2, Canada
- Department of Medicine, Division of Gastroenterology, St. Michael’s Hospital, Unity Health Toronto, Toronto, ON M5B 1W8, Canada
| | - Sami A. Chadi
- Sprott Department of Surgery, Division of General Surgery, Toronto General Hospital, University Health Network, Toronto, ON M5G 2C4, Canada
- Department of Surgery, University of Toronto, Toronto, ON M5T 1P5, Canada
| | - Ronald L. Burkes
- Department of Medicine, Mount Sinai Hospital, Sinai Health, Toronto, ON M5G 1X5, Canada
- Department of Medicine, Temerty Faculty of Medicine, University of Toronto, Toronto, ON M5S 3H2, Canada
| | - Maya Pankiw
- Department of Medicine, Mount Sinai Hospital, Sinai Health, Toronto, ON M5G 1X5, Canada
| | - Christine Brezden-Masley
- Department of Medicine, Mount Sinai Hospital, Sinai Health, Toronto, ON M5G 1X5, Canada
- Department of Medicine, Temerty Faculty of Medicine, University of Toronto, Toronto, ON M5S 3H2, Canada
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Talboom K, Borstlap WAA, Roodbeen SX, Bruns ERJ, Buskens CJ, Hompes R, Tytgat KMAJ, Tuynman JB, Consten ECJ, Heuff G, Kuiper T, van Geloven AAW, Veldhuis GJ, van der Hoeven JAB, Gerhards MF, Sietses C, Spinelli A, van de Ven AWH, van der Zaag ES, Westerterp M, van Westreenen HL, Dijkgraaf ML, Juffermans NP, Bemelman WA, Hess D, Swank HA, Scholten L, van der Bilt JDW, Jansen MA, van Duijvendijk P, Bezuur D, Carvello M, Foppa C, de Vos tot Nederveen Cappel WH, Geitenbeek RTJ, van Woensel L, De Castro SMM, Wientjes C, van Oostendorp S. 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. Lancet Haematol 2023; 10:e250-e260. [PMID: 36863386 DOI: 10.1016/s2352-3026(22)00402-1] [Citation(s) in RCA: 22] [Impact Index Per Article: 11.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/01/2022] [Revised: 11/17/2022] [Accepted: 12/08/2022] [Indexed: 03/03/2023]
Abstract
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<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.
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Affiliation(s)
- Kevin Talboom
- Department of Surgery, Amsterdam UMC, Location AMC, Amsterdam, Netherlands
| | | | - Sapho X Roodbeen
- Department of Surgery, Amsterdam UMC, Location AMC, Amsterdam, Netherlands
| | - Emma R J Bruns
- Department of Surgery, Amsterdam UMC, Location AMC, Amsterdam, Netherlands
| | | | - Roel Hompes
- Department of Surgery, Amsterdam UMC, Location AMC, Amsterdam, Netherlands
| | | | - Jurriaan B Tuynman
- Department of Surgery, Amsterdam UMC, Location VUmc, Amsterdam, Netherlands
| | - Esther C J Consten
- Department of Surgery, Meander Medical Centre, Amersfoort, Netherlands; Department of Surgery, University Medical Centre Groningen, Groningen, Netherlands
| | - Gijsbert Heuff
- Department of Surgery, Spaarne Gasthuis, Hoofddorp, Netherlands
| | - Teaco Kuiper
- Department of Gastroenterology, Amstelland Hospital, Amstelveen, Netherlands
| | | | - Gerrit J Veldhuis
- Department of Internal Medicine, Antonius Hospital, Sneek, Netherlands
| | | | - Michael F Gerhards
- Department of Surgery, Onze Lieve Vrouwe Gasthuis, Amsterdam, Netherlands
| | - Colin Sietses
- Department of Surgery, Hospital Gelderse Vallei, Ede, Netherlands
| | - Antonino Spinelli
- Department of Biomedical Sciences, Humanitas University, Pieve Emanuele, Milan, Italy; Division of Colon and Rectal Surgery, IRCCS Humanitas Research Hospital, Rozzano, Milan, Italy
| | | | | | | | | | - Marcel L Dijkgraaf
- Epidemiology and Data Science, Amsterdam UMC, location University of Amsterdam, Amsterdam, Netherlands; Amsterdam Public Health Methodology, Amsterdam, Netherlands
| | - Nicole P Juffermans
- Department of Internal Medicine, Amsterdam UMC, Location AMC, Amsterdam, Netherlands
| | - Wilhelmus A Bemelman
- Department of Surgery, Amsterdam UMC, Location AMC, Amsterdam, Netherlands; IBD Unit, Gastroenterology and Endoscopy, IRCCS Ospedale San Raffaele and University Vita Salute San Raffaele, Milan, Italy.
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Huang L, Li W, Lu Y, Ju Q, Ouyang M. Iron metabolism in colorectal cancer. Front Oncol 2023; 13:1098501. [PMID: 36910614 PMCID: PMC9992732 DOI: 10.3389/fonc.2023.1098501] [Citation(s) in RCA: 9] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/15/2022] [Accepted: 02/09/2023] [Indexed: 02/25/2023] Open
Abstract
Iron, as one of the essential trace elements in the human body, is involved in a wide range of critical biochemical reactions and physiological processes, including the maintenance of the normal cell cycle, mitochondrial function, nucleotide metabolism, and immune response. In this context, iron is naturally associated with cancer occurrence. Cellular iron deficiency can induce apoptosis, however, iron can also engage in potentially harmful reactions that produce free radicals because of its capacity to gain and lose electrons. Studies suggest that dietary iron, particularly heme iron, may be one of the leading causes of colorectal cancer (CRC). Moreover, patients with CRC have abnormal iron absorption, storage, utilization, and exportation. Therefore, iron is crucial for the development and progression of CRC. Elaborating on the alterations in iron metabolism during the onset and advancement of CRC would help to further explain the role and mechanism of iron inside the body. Thus, we reviewed the alterations in numerous iron metabolism-related molecules and their roles in CRC, which may provide new clues between iron metabolism and CRC.
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Affiliation(s)
- Luji Huang
- Department of Gastrointestinal Surgery, Shunde Hospital, Southern Medical University (The First People's Hospital of Shunde Foshan), Foshan, Guangdong, China.,The Second School of Clinical Medicine, Southern Medical University, Guangzhou, Guangdong, China
| | - Wangji Li
- Department of Gastrointestinal Surgery, Shunde Hospital, Southern Medical University (The First People's Hospital of Shunde Foshan), Foshan, Guangdong, China.,The Second School of Clinical Medicine, Southern Medical University, Guangzhou, Guangdong, China
| | - Yan Lu
- Good Clinical Practice (GCP) Center, Shunde Hospital, Southern Medical University (The First People's Hospital of Shunde Foshan), Guangdong, China
| | - Qinuo Ju
- Guangdong Country Garden School, Shunde, Foshan, Guangdong, China
| | - Manzhao Ouyang
- Department of Gastrointestinal Surgery, Shunde Hospital, Southern Medical University (The First People's Hospital of Shunde Foshan), Foshan, Guangdong, China
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Decruyenaere A, Kortbeek K, Delanghe S, Rottey S, Denys H, Lapeire L. Incidence, evolution and risk factors of hypophosphatemia in patients with solid tumors receiving ferric carboxymaltose: a retrospective cohort study. Acta Clin Belg 2022:1-10. [DOI: 10.1080/17843286.2022.2153465] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
Affiliation(s)
- Alexander Decruyenaere
- Department of Internal Medicine and Pediatrics, Ghent University, Ghent, Belgium
- Department of Medical Oncology, Ghent University Hospital, Ghent, Belgium
| | - Koen Kortbeek
- Department of Medical Oncology, University Hospital Brussels, Brussels, Belgium
| | - Sigurd Delanghe
- Department of Internal Medicine and Pediatrics, Ghent University, Ghent, Belgium
- Department of Nephrology, Ghent University Hospital, Ghent, Belgium
| | - Sylvie Rottey
- Department of Internal Medicine and Pediatrics, Ghent University, Ghent, Belgium
- Department of Medical Oncology, Ghent University Hospital, Ghent, Belgium
| | - Hannelore Denys
- Department of Internal Medicine and Pediatrics, Ghent University, Ghent, Belgium
- Department of Medical Oncology, Ghent University Hospital, Ghent, Belgium
| | - Lore Lapeire
- Department of Internal Medicine and Pediatrics, Ghent University, Ghent, Belgium
- Department of Medical Oncology, Ghent University Hospital, Ghent, Belgium
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Waterland JL, Ismail H, Granger CL, Patrick C, Denehy L, Riedel B. Prehabilitation in high-risk patients scheduled for major abdominal cancer surgery: a feasibility study. Perioper Med (Lond) 2022; 11:32. [PMID: 35996196 PMCID: PMC9396890 DOI: 10.1186/s13741-022-00263-2] [Citation(s) in RCA: 10] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/08/2021] [Accepted: 05/15/2022] [Indexed: 11/17/2022] Open
Abstract
Background Patients presenting for major surgery with low cardiorespiratory fitness (deconditioning) and other modifiable risk factors are at increased risk of postoperative complications. This study investigated the feasibility of delivering prehabilitation in high-risk patients scheduled for major abdominal cancer surgery. Methods Eligible patients in this single-center cohort study included patients with poor fitness (objectively assessed by cardiopulmonary exercise testing, CPET) scheduled for elective major abdominal cancer surgery. Patients were recruited to participate in a prehabilitation program that spanned up to 6 weeks pre-operatively and comprised aerobic and resistance exercise training, breathing exercise, and nutritional support. The primary outcome assessed pre-specified feasibility targets: recruitment >70%, retention >85%, and intervention adherence >70%. Secondary outcomes were assessed for improved pre-operative functional status and health-related quality of life and for postoperative complications. Results Eighty-two (34%) out of 238 patients screened between April 2018 and December 2019 were eligible for recruitment. Fifty (61%) patients (52% males) with a median age of 71 (IQR, 63–77) years participated in the study. Baseline oxygen consumption the at anaerobic threshold and at peak exercise (mean±SD: 9.8±1.8 and 14.0±2.9 mL/kg/min, respectively) confirmed the deconditioned state of the study cohort. The retention rate within the prehabilitation program was 84%, with 42 participants returning for repeat CPET testing. While >60% of participants preferred to do home-based prehabilitation, adherence to the intervention was low—with only 12 (28%) and 15 (35%) of patients having self-reported compliance >70% with their exercise prescriptions. Conclusion Our prehabilitation program in high-risk cancer surgery patients did not achieve pre-specified targets for recruitment, retention, and self-reported program adherence. These findings underpin the importance of implementation research and strategies for the prehabilitation programs in major surgery. Trial registration Australian New Zealand Clinical Trials Registry (ACTRN12620000073909) retrospectively registered. Supplementary Information The online version contains supplementary material available at 10.1186/s13741-022-00263-2.
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Affiliation(s)
- Jamie L Waterland
- Peter MacCallum Cancer Centre, Department of Anaesthesia, Perioperative and Pain Medicine, Melbourne, Australia. .,Department of Physiotherapy, The University of Melbourne, Melbourne, Australia. .,Peter MacCallum Cancer Centre, Division of Allied Health, Melbourne, Australia.
| | - Hilmy Ismail
- Peter MacCallum Cancer Centre, Department of Anaesthesia, Perioperative and Pain Medicine, Melbourne, Australia.,The University of Melbourne, Centre for Integrated Critical Care, Melbourne, Australia
| | - Catherine L Granger
- Department of Physiotherapy, The University of Melbourne, Melbourne, Australia.,Physiotherapy Department, The Royal Melbourne Hospital, Melbourne, Australia
| | - Cameron Patrick
- The University of Melbourne, Statistical Consulting Centre, School of Mathematics and Statistics, Melbourne, Australia
| | - Linda Denehy
- Department of Physiotherapy, The University of Melbourne, Melbourne, Australia.,Peter MacCallum Cancer Centre, Division of Allied Health, Melbourne, Australia
| | - Bernhard Riedel
- Peter MacCallum Cancer Centre, Department of Anaesthesia, Perioperative and Pain Medicine, Melbourne, Australia.,The University of Melbourne, Centre for Integrated Critical Care, Melbourne, Australia.,The Sir Peter MacCallum Department of Oncology, University of Melbourne, Melbourne, Australia
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Meyer J, Cirocchi R, Di Saverio S, Ris F, Wheeler J, Davies RJ. Pre-operative iron increases haemoglobin concentration before abdominal surgery: a systematic review and meta-analysis of randomized controlled trials. Sci Rep 2022; 12:2158. [PMID: 35140245 PMCID: PMC8828750 DOI: 10.1038/s41598-022-05283-y] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/26/2021] [Accepted: 12/08/2021] [Indexed: 11/09/2022] Open
Abstract
Professional surgical societies recommend the identification and treatment of pre-operative anaemia in patients scheduled for abdominal surgery. Our aim was to determine if pre-operative iron allows correction of haemoglobin concentration and decreased incidence of peri-operative blood transfusion in patients undergoing major abdominal surgery. MEDLINE, Embase and CENTRAL were searched for RCTs written in English and assessing the effect of pre-operative iron on the incidence of peri-operative allogeneic blood transfusion in patients undergoing major abdominal surgery. Pooled relative risk (RR), risk difference (RD) and mean difference (MD) were obtained using models with random effects. Heterogeneity was assessed using the Q-test and quantified using the I2 value. Four RCTs were retained for analysis out of 285 eligible articles. MD in haemoglobin concentration between patients with pre-operative iron and patients without pre-operative iron was of 0.81 g/dl (3 RCTs, 95% CI 0.30 to 1.33, I2: 60%, p = 0.002). Pre-operative iron did not lead to reduction in the incidence of peri-operative blood transfusion in terms of RD (4 RCTs, RD: - 0.13, 95% CI - 0.27 to 0.01, I2: 65%, p = 0.07) or RR (4 RCTs, RR: 0.57, 95% CI 0.30 to 1.09, I2: 64%, p = 0.09). To conclude, pre-operative iron significantly increases haemoglobin concentration by 0.81 g/dl before abdominal surgery but does not reduce the need for peri-operative blood transfusion. Important heterogeneity exists between existing RCTs in terms of populations and interventions. Future trials should target patients suffering from iron-deficiency anaemia and assess the effect of intervention on anaemia-related complications.
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Affiliation(s)
- Jeremy Meyer
- Colorectal Unit, Addenbrooke's Hospital, Cambridge NHS Foundation Trust, Cambridge, UK.
- Division of Digestive Surgery, University Hospitals of Geneva, Geneva, Switzerland.
- Medical School, University of Geneva, Geneva, Switzerland.
| | | | | | - Frédéric Ris
- Division of Digestive Surgery, University Hospitals of Geneva, Geneva, Switzerland
- Medical School, University of Geneva, Geneva, Switzerland
| | - James Wheeler
- Colorectal Unit, Addenbrooke's Hospital, Cambridge NHS Foundation Trust, Cambridge, UK
| | - Richard Justin Davies
- Colorectal Unit, Addenbrooke's Hospital, Cambridge NHS Foundation Trust, Cambridge, UK
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Bojesen RD, Eriksen JR, Vogelsang RP, Grube C, Forman JL, Gogenür I. The dynamic effects of preoperative intravenous iron in anaemic patients undergoing surgery for colorectal cancer. Colorectal Dis 2021; 23:2550-2558. [PMID: 34166572 DOI: 10.1111/codi.15789] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/13/2021] [Revised: 06/02/2021] [Accepted: 06/18/2021] [Indexed: 12/21/2022]
Abstract
AIM The aim of this study was to describe the dynamic changes in blood work following individual adjusted dosage of intravenously administered iron(III) isomaltoside in a 4-week period prior to surgery in patients with colorectal cancer. METHODS This was a single-centre, observational cohort study with prospectively collected data, including patients with colorectal cancer receiving preoperative treatment with iron(III) isomaltoside. Blood samples were taken at baseline, 1 week, 2 weeks and 4 weeks after initial treatment. Sixty-two patients were included in the study. RESULTS Sixty-two patients were included for final analysis. The mean increase in haemoglobin was 0.77 g/dl (95% CI 0.52-1.03 g/dl, P < 0.0001) at week 1, 1.5 g/dl (95% CI 1.21-1.80 g/dl, P < 0.0001) at week 2 and 2.13 g/dl (95% CI 1.71-2.55 g/dl, P < 0.0001) at week 4. Patients with severe anaemia (<9.02 g/dl) showed the largest increase in haemoglobin during the treatment course (2.92 g/dl, 95% CI 2.27-3.58 g/dl, P < 0.0001). Patients with mild anaemia (>10.31 g/dl) did not show a significant increase (0.66 g/dl, 95% CI -0.29-1.61 g/dl, P = 0.17). The mean of transferrin saturation after 4 weeks was 8% (95% CI 6%-10%, P < 0.0001). CONCLUSIONS After intravenously administered iron, patients with severe anaemia had the most substantial increase in haemoglobin, and the increase was largest after 4 weeks. Patients with mild anaemia did not have an increase in haemoglobin during the treatment course. The vast majority of patients still had iron deficiency at surgery 4 weeks after the initial treatment.
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Affiliation(s)
- Rasmus Dahlin Bojesen
- Department of Surgery, Slagelse Hospital, Slagelse, Denmark.,Centre for Surgical Science, Zealand University Hospital, Køge, Denmark
| | | | | | - Camilla Grube
- Department of Surgery, Slagelse Hospital, Slagelse, Denmark.,Centre for Surgical Science, Zealand University Hospital, Køge, Denmark
| | - Julie Lyng Forman
- Section of Biostatistics, Department of Public Health, University of Copenhagen, Copenhagen, Denmark
| | - Ismail Gogenür
- Centre for Surgical Science, Zealand University Hospital, Køge, Denmark
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Abstract
Excessive gut luminal iron contributes to the initiation and progression of colorectal cancer. However, emerging evidence suggests that reduced iron intake and low systemic iron levels are also associated with the pathogenesis of colorectal cancer. This is important because patients with colorectal cancer often present with iron deficiency. Iron is necessary for appropriate immunological functions; hence, iron deficiency may hinder cancer immunosurveillance and potentially modify the tumor immune microenvironment, both of which may assist cancer development. This is supported by studies showing that patients with colorectal cancer with iron deficiency have inferior outcomes and reduced response to therapy. Here, we provide an overview of the immunological consequences of iron deficiency and suggest ensuring adequate iron therapy to limit these outcomes.
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Affiliation(s)
- Oliver Phipps
- O. Phipps, M.J. Brookes, and H.O. Al-Hassi are with the Research Institute in Healthcare Science, Faculty of Science and Engineering, University of Wolverhampton, Wolverhampton, United Kingdom
| | - Matthew J Brookes
- O. Phipps, M.J. Brookes, and H.O. Al-Hassi are with the Research Institute in Healthcare Science, Faculty of Science and Engineering, University of Wolverhampton, Wolverhampton, United Kingdom.,Royal Wolverhampton Hospitals NHS Trust, Gastroenterology Unit Wolverhampton, Wolverhampton, United Kingdom
| | - Hafid O Al-Hassi
- O. Phipps, M.J. Brookes, and H.O. Al-Hassi are with the Research Institute in Healthcare Science, Faculty of Science and Engineering, University of Wolverhampton, Wolverhampton, United Kingdom
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9
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Effectiveness of Iron Supplementation With or Without Erythropoiesis-Stimulating Agents on Red Blood Cell Utilization in Patients With Preoperative Anaemia Undergoing Elective Surgery: A Systematic Review and Meta-Analysis. Transfus Med Rev 2021; 35:103-124. [PMID: 33965294 DOI: 10.1016/j.tmrv.2021.03.004] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/06/2020] [Revised: 03/24/2021] [Accepted: 03/30/2021] [Indexed: 02/07/2023]
Abstract
Patient Blood Management (PBM) is an evidence-based, multidisciplinary, patient-centred approach to optimizing the care of patients who might need a blood transfusion. This systematic review aimed to collect the best available evidence on the effectiveness of preoperative iron supplementation with or without erythropoiesis-stimulating agents (ESAs) on red blood cell (RBC) utilization in all-cause anaemic patients scheduled for elective surgery. Five databases and two trial registries were screened. Primary outcomes were the number of patients and the number of RBC units transfused. Effect estimates were synthesized by conducting meta-analyses. GRADE (Grades of Recommendation, Assessment, Development and Evaluation) was used to assess the certainty of evidence. We identified 29 randomized controlled trials (RCTs) and 2 non-RCTs comparing the effectiveness of preoperative iron monotherapy, or iron + ESAs, to control (no treatment, usual care, placebo). We found that: (1) IV and/or oral iron monotherapy may not result in a reduced number of units transfused and IV iron may not reduce the number of patients transfused (low-certainty evidence); (2) uncertainty exists whether the administration route of iron therapy (IV vs oral) differentially affects RBC utilization (very low-certainty evidence); (3) IV ferric carboxymaltose monotherapy may not result in a different number of patients transfused compared to IV iron sucrose monotherapy (low-certainty evidence); (4) oral iron + ESAs probably results in a reduced number of patients transfused and number of units transfused (moderate-certainty evidence); (5) IV iron + ESAs may result in a reduced number of patients transfused (low-certainty evidence); (6) oral and/or IV iron + ESAs probably results in a reduced number of RBC units transfused in transfused patients (moderate-certainty evidence); (7) uncertainty exists about the effect of oral and/or IV iron + ESAs on the number of patients requiring transfusion of multiple units (very low-certainty evidence). Effect estimates of different haematological parameters and length of stay were synthesized as secondary outcomes. In conclusion, in patients with anaemia of any cause scheduled for elective surgery, the preoperative administration of iron monotherapy may not result in a reduced number of patients or units transfused (low-certainty evidence). Iron supplementation in addition to ESAs probably results in a reduced RBC utilization (moderate-certainty evidence).
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10
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Phipps O, Al-Hassi HO, Quraishi MN, Kumar A, Brookes MJ. Influence of Iron on the Gut Microbiota in Colorectal Cancer. Nutrients 2020; 12:nu12092512. [PMID: 32825236 PMCID: PMC7551435 DOI: 10.3390/nu12092512] [Citation(s) in RCA: 27] [Impact Index Per Article: 5.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/09/2020] [Revised: 08/07/2020] [Accepted: 08/14/2020] [Indexed: 12/11/2022] Open
Abstract
Perturbations of the colonic microbiota can contribute to the initiation and progression of colorectal cancer, leading to an increase in pathogenic bacteria at the expense of protective bacteria. This can contribute to disease through increasing carcinogenic metabolite/toxin production, inducing inflammation, and activating oncogenic signaling. To limit disease progression, external factors that may influence the colonic microbiota need to be considered in patients with colorectal cancer. One major factor that can influence the colonic microbiota is iron. Iron is an essential micronutrient that is required by both prokaryotes and eukaryotes for cellular function. Most pathogenic bacteria have heightened iron acquisition mechanisms and therefore tend to outcompete protective bacteria for free iron. Colorectal cancer patients often present with anemia due to iron deficiency, and thus they require iron therapy. Depending upon the route of administration, iron therapy has the potential to contribute to a procarciongenic microbiota. Orally administered iron is the common treatment for anemia in these patients but can lead to an increased gut iron concentration. This suggests the need to reassess the route of iron therapy in these patients. Currently, this has only been assessed in murine studies, with human trials being necessary to unravel the potential microbial outcomes of iron therapy.
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Affiliation(s)
- Oliver Phipps
- Research Institute in Healthcare Science, Faculty of Science and Engineering, University of Wolverhampton, Wolverhampton WV1 1LY, UK; (H.O.A.-H.); (A.K.); (M.J.B.)
- Correspondence:
| | - Hafid O. Al-Hassi
- Research Institute in Healthcare Science, Faculty of Science and Engineering, University of Wolverhampton, Wolverhampton WV1 1LY, UK; (H.O.A.-H.); (A.K.); (M.J.B.)
| | - Mohammed N. Quraishi
- Institute of Cancer and Genomic Sciences, University of Birmingham, Birmingham B15 2TT, UK;
| | - Aditi Kumar
- Research Institute in Healthcare Science, Faculty of Science and Engineering, University of Wolverhampton, Wolverhampton WV1 1LY, UK; (H.O.A.-H.); (A.K.); (M.J.B.)
- Royal Wolverhampton Hospitals NHS Trust, Gastroenterology Unit, Wolverhampton WV10 0QP, UK
| | - Matthew J. Brookes
- Research Institute in Healthcare Science, Faculty of Science and Engineering, University of Wolverhampton, Wolverhampton WV1 1LY, UK; (H.O.A.-H.); (A.K.); (M.J.B.)
- Royal Wolverhampton Hospitals NHS Trust, Gastroenterology Unit, Wolverhampton WV10 0QP, UK
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Postoperative ERAS Interventions Have the Greatest Impact on Optimal Recovery: Experience With Implementation of ERAS Across Multiple Hospitals. Ann Surg 2019; 267:992-997. [PMID: 29303803 DOI: 10.1097/sla.0000000000002632] [Citation(s) in RCA: 126] [Impact Index Per Article: 21.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
BACKGROUND Enhanced recovery after surgery (ERAS) programs incorporate evidence-based practices to minimize perioperative stress, gut dysfunction, and promote early recovery. However, it is unknown which components have the greatest impact. OBJECTIVE This study aims to determine which components of ERAS programs have the largest impact on recovery for patients undergoing colorectal surgery. METHODS An iERAS program was implemented in 15 academic hospitals. Data were collected prospectively. Patients were considered compliant if >75% of the preoperative, intraoperative, and postoperative predefined interventions were adhered to. Optimal recovery was defined as discharge within 5 days of surgery with no major complications, no readmission to hospital, and no mortality. Multivariable analysis was used to model the impact of compliance and technique on optimal recovery. RESULTS Overall, 2876 patients were enrolled. Colon resections were performed in 64.7% of patients and 52.9% had a laparoscopic procedure. Only 20.1% of patients were compliant with all phases of the pathway. The poorest compliance rate was for postoperative interventions (40.3%) which was independently associated with an increase in optimal recovery (RR = 2.12, 95% CI 1.81-2.47). Compliance with ERAS interventions remained associated with improved outcomes whether surgery was performed laparoscopically (RR = 1.55, 95% CI 1.23-1.96) or open (RR = 2.29, 95% CI 1.68-3.13). However, the impact of ERAS compliance was significantly greater in the open group (P < 0.001). CONCLUSIONS Postoperative compliance is the most difficult to achieve but is most strongly associated with optimal recovery. Although our data support that ERAS has more effect in patients undergoing open surgery, it also showed a significant impact on patients treated with a laparoscopic approach.
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Ferrer‐Barceló L, Sanchis Artero L, Sempere García‐Argüelles J, Canelles Gamir P, P. Gisbert J, Ferrer‐Arranz LM, Monzó Gallego A, Plana Campos L, Huguet Malavés JM, Luján Sanchis M, Ruiz Sánchez L, Barceló Cerdá S, Medina Chuliá E. Randomised clinical trial: intravenous vs oral iron for the treatment of anaemia after acute gastrointestinal bleeding. Aliment Pharmacol Ther 2019; 50:258-268. [PMID: 31197861 PMCID: PMC6771644 DOI: 10.1111/apt.15327] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/09/2019] [Revised: 01/15/2019] [Accepted: 05/08/2019] [Indexed: 12/13/2022]
Abstract
BACKGROUND Acute gastrointestinal bleeding is prevalent condition and iron deficiency anaemia is a common comorbidity, yet anaemia treatment guidelines for affected patients are lacking. AIM To compare efficacy and safety of intravenous ferric carboxymaltose (FCM) and oral ferrous sulphate (FeSulf) in patients with anaemia secondary to non-variceal gastrointestinal bleeding METHODS: A prospective 42-day study randomised 61 patients with haemoglobin <10 g/dL upon discharge (Day 0) to receive FCM (n = 29; Day 0: 1000 mg, Day 7: 500 or 1000 mg; per label) or FeSulf (n = 32; 325 mg/12 hours for 6 weeks). Outcome measures were assessed on Days 0 (baseline), 7, 21 and 42. The primary outcome was complete response (haemoglobin ≥12 g/dL [women], ≥13 g/dL [men]) after 6 weeks. RESULTS A higher proportion of complete response was observed in the FCM vs the FeSulf group at Days 21 (85.7% vs 45.2%; P = 0.001) and 42 (100% vs 61.3%; P < 0.001). Additionally, the percentage of patients with partial response (haemoglobin increment ≥2 g/dL from baseline) was significantly higher in the FCM vs the FeSulf group (Day 21:100% vs 67.7%; P = 0.001, Day 42:100% vs 74.2%; P = 0.003). At Day 42, normalisation of transferrin saturation to 25% or greater was observed in 76.9% of FCM vs 24.1% of FeSulf-treated patients (P < 0.001). No patient in the FCM group reported any adverse event vs 10 patients in the FeSulf group. CONCLUSION FCM provided greater and faster Hb increase and iron repletion, and was better tolerated than FeSulf in patients with iron deficiency anaemia secondary to non-variceal acute gastrointestinal bleeding.
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Affiliation(s)
- Luis Ferrer‐Barceló
- Hospital General Universitario de ValenciaServicio de Patología DigestivaValenciaSpain
| | - Laura Sanchis Artero
- Hospital General Universitario de ValenciaServicio de Patología DigestivaValenciaSpain
| | | | - Pilar Canelles Gamir
- Hospital General Universitario de ValenciaServicio de Patología DigestivaValenciaSpain
| | - Javier P. Gisbert
- Hospital Universitario de La Princesa, Instituto de Investigación Sanitaria Princesa (IIS‐IP) y Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd)MadridSpain
| | | | - Ana Monzó Gallego
- Hospital General Universitario de ValenciaServicio de Patología DigestivaValenciaSpain
| | - Lydia Plana Campos
- Hospital General Universitario de ValenciaServicio de Patología DigestivaValenciaSpain
| | | | - Marisol Luján Sanchis
- Hospital General Universitario de ValenciaServicio de Patología DigestivaValenciaSpain
| | - Lucía Ruiz Sánchez
- Hospital General Universitario de ValenciaServicio de Patología DigestivaValenciaSpain
| | - Susana Barceló Cerdá
- Departamento de Estadística e Investigación Operativa y CalidadUniversitat Politècnica de ValènciaValenciaSpain
| | - Enrique Medina Chuliá
- Hospital General Universitario de ValenciaServicio de Patología DigestivaValenciaSpain
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The Association of Preoperative Anemia and the Postoperative Course and Oncological Outcome in Patients Undergoing Rectal Cancer Surgery: A Multicenter Snapshot Study. Dis Colon Rectum 2019; 62:823-831. [PMID: 31188183 DOI: 10.1097/dcr.0000000000001360] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
Abstract
BACKGROUND There is still controversy about the relationship between preoperative anemia and outcomes after rectal cancer surgery. OBJECTIVE The aim of this study was to analyze the association between preoperative anemia and postoperative complications and the survival of patients undergoing surgery for rectal cancer in the era of laparoscopic surgery and modern perioperative care. DESIGN This was a cohort study. SETTINGS Data were gathered from 71 hospitals in The Netherlands. PATIENTS Patients who underwent resection for rectal cancer in 2011, for whom preoperative hemoglobin level was registered, were included. INTERVENTIONS(S) There were no interventions. MAIN OUTCOME MEASURES Short-term outcome parameters were any postoperative complication or mortality within 30 days postoperatively, and pelvic infectious complications defined as anastomotic leakage and presacral abscess. Long-term outcomes were chronic sinus diagnosed at any time during 3-year follow-up, 3-year local and distant recurrence rates, and 3-year overall survival. RESULTS Of 2095 patients, 1857 had a registered preoperative hemoglobin level; 576 (31%) of these patients anemic and 1281 (69%) were nonanemic. Preoperative anemia was not independently associated with postoperative complications (HR, 1.1; 95% CI, 0.9-1.4; p = 0·24) or 30-day mortality (HR, 1.4, 95% CI, 0.7-2.8; p = 0·29). Preoperative anemia was associated with 3-year overall survival (HR, 2.1; 95% CI, 1.7-2.5; p < 0.0001), after multivariable analysis (HR, 1.4; 95% CI, 1.1-1.8; p = 0·008), and with local recurrence rate (HR, 1.6; 95% CI, 1.1-2.4; p = 0.026), but not with distant recurrence rate (HR, 1.2; 95% CI, 1.0-1.5; p = 0.054). LIMITATIONS Preoperative anemia appeared to have only limited association with postoperative and disease-specific outcome after rectal cancer surgery in contrast to published meta-analysis of small historical series. CONCLUSIONS Anemia is associated with overall survival. It might be considered as one of the warning signs in identifying high-risk patients. See Video Abstract at http://links.lww.com/DCR/A913.
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Intravenous iron versus oral iron or observation for gastrointestinal malignancies: a systematic review. Eur J Gastroenterol Hepatol 2019; 31:799-808. [PMID: 31082997 DOI: 10.1097/meg.0000000000001433] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/29/2022]
Abstract
BACKGROUND Anemia is a common condition in patients with gastrointestinal cancer. Current evidence for the use of intravenous compared with oral iron in this clinical setting is inconclusive. A systematic review was performed to assess evidence on the efficacy of intravenous iron versus oral/observation in gastrointestinal cancer patients in the preoperative and postoperative setting. MATERIALS AND METHODS We searched Medline and Embase from inception until December 2017 with no language restrictions. Outcomes included hemoglobin response, red blood cell transfusion, and adverse events. Screening, data abstraction, and risk of bias appraisal were performed by two independent reviewers. The risk of bias was assessed using the Cochrane tools for randomized and nonrandomized studies. RESULTS A total of 10 studies (three randomized-controlled trials and seven nonrandomized studies) were included. Of the six preoperative studies, five reported that hemoglobin was significantly higher in the intravenous group compared with oral iron/observation. Among the four postoperative studies, three studies suggested that hemoglobin was significantly higher in the intravenous group compared with oral iron/observation. The overall risk of bias for all randomized-controlled trials was low. Quality assessments for nonrandomized studies found the risk of bias to be moderate for four studies and critical for three studies. CONCLUSION Despite the limitations of the current body of evidence, there is a likely benefit to the use of intravenous iron in this patient population. Further confirmatory research is needed to draw empirical conclusions.
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Wilson MJ, Koopman-van Gemert AW, Harlaar JJ, Jeekel J, Zwaginga JJ, Schipperus M. Patient blood management in colorectal cancer patients: a survey among Dutch gastroenterologists, surgeons, and anesthesiologists. Transfusion 2018; 58:2345-2351. [DOI: 10.1111/trf.14807] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/01/2018] [Revised: 04/25/2018] [Accepted: 04/27/2018] [Indexed: 12/15/2022]
Affiliation(s)
- Michael J. Wilson
- TRIP Hemovigilance and Biovigilance Office; Leiden The Netherlands
- Department of Surgery, Erasmus University Medical Center; Rotterdam The Netherlands
| | | | - Joris J. Harlaar
- Department of Surgery; VU Medical Center; Amsterdam The Netherlands
- Department of Surgery; Westfries Gasthuis; Hoorn The Netherlands
| | - Johannes Jeekel
- Department of Neuroscience; Erasmus University Medical Center; Rotterdam The Netherlands
| | - Jaap Jan Zwaginga
- Center for Clinical Transfusion Research; Sanquin Research
- Department of Immunohematology and Blood Transfusion; Leiden University Medical Center; Leiden The Netherlands
| | - Martin Schipperus
- TRIP Hemovigilance and Biovigilance Office; Leiden The Netherlands
- Department of Hematology; Haga Teaching Hospital; The Hague The Netherlands
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Bhandari S, Pereira DIA, Chappell HF, Drakesmith H. Intravenous Irons: From Basic Science to Clinical Practice. Pharmaceuticals (Basel) 2018; 11:E82. [PMID: 30150598 PMCID: PMC6161004 DOI: 10.3390/ph11030082] [Citation(s) in RCA: 48] [Impact Index Per Article: 6.9] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/01/2018] [Revised: 08/22/2018] [Accepted: 08/23/2018] [Indexed: 02/07/2023] Open
Abstract
Iron is an essential trace mineral necessary for life, and iron deficiency anaemia (IDA) is one of the most common haematological problems worldwide, affecting a sixth of the global population. Principally linked to poverty, malnutrition and infection in developing countries, in Western countries the pathophysiology of IDA is primarily linked to blood loss, malabsorption and chronic disease. Oral iron replacement therapy is a simple, inexpensive treatment, but is limited by gastrointestinal side effects that are not inconsequential to some patients and are of minimal efficacy in others. Third generation intravenous (IV) iron therapies allow rapid and complete replacement dosing without the toxicity issues inherent with older iron preparations. Their characteristic, strongly-bound iron-carbohydrate complexes exist as colloidal suspensions of iron oxide nanoparticles with a polynuclear Fe(III)-oxyhydroxide/oxide core surrounded by a carbohydrate ligand. The physicochemical differences between the IV irons include mineral composition, crystalline structure, conformation, size and molecular weight, but the most important difference is the carbohydrate ligand, which influences complex stability, iron release and immunogenicity, and which is a unique feature of each drug. Recent studies have highlighted different adverse event profiles associated with third-generation IV irons that reflect their different structures. The increasing clinical evidence base has allayed safety concerns linked to older IV irons and widened their clinical use. This review considers the properties of the different IV irons, and how differences might impact current and future clinical practice.
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Affiliation(s)
- Sunil Bhandari
- Hull and East Yorkshire Hospitals NHS Trust and Hull York Medical School, Hull HU3 2JZ, UK.
| | - Dora I A Pereira
- Department of Pathology, University of Cambridge, Cambridge CB2 1QP, UK.
- MRC Unit The Gambia at the London School of Hygiene & Tropical Medicine, Banjul, Republic of Gambia.
| | - Helen F Chappell
- School of Food Science and Nutrition, University of Leeds, Leeds LS2 9JT, UK.
| | - Hal Drakesmith
- MRC Human Immunology Unit, Weatherall Institute of Molecular Medicine, University of Oxford, Headington, Oxford OX3 9DS, UK.
- Haematology Theme Oxford Biomedical Research Centre, Oxford OX3 9DS, UK.
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The effect of intravenous iron therapy on long-term survival in anaemic colorectal cancer patients: Results from a matched cohort study. Surg Oncol 2018; 27:192-199. [DOI: 10.1016/j.suronc.2018.03.005] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/31/2017] [Revised: 03/02/2018] [Accepted: 03/26/2018] [Indexed: 12/27/2022]
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The prognostic role of perioperative allogeneic blood transfusions in gastric cancer patients undergoing curative resection: A systematic review and meta-analysis of non-randomized, adjusted studies. Eur J Surg Oncol 2018; 44:404-419. [PMID: 29398320 DOI: 10.1016/j.ejso.2018.01.006] [Citation(s) in RCA: 18] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/06/2016] [Revised: 08/25/2017] [Accepted: 01/03/2018] [Indexed: 12/18/2022] Open
Abstract
The impact of allogeneic perioperative blood transfusions (APTs) on the prognosis of gastric cancer patients undergoing curative-intent gastrectomy is still a highly debated topic. Two meta-analyses were published in 2015, and new studies report conflicting results. A literature review was conducted using PubMed, Scopus, the Cochrane Central Register of Controlled Trials and the Cochrane Database of Systematic Reviews, updated to March 1, 2016. Thirty-eight non-randomized studies reporting data on overall survival (OS), disease-free survival (DFS), disease-specific survival (DSS) and postoperative complications (PCs) were included. An inverse variance random-effects meta-analysis was conducted. APTs showed an association with worse OS, DFS, DSS and an increased number of PCs. The hazard ratio (HR) for OS was 1.49, with a 95% confidence interval (95% CI) of 1.32-1.69 (p < .00001; Q-test p = .001, I-squared = 56%). After outlier exclusion, the HR for OS was 1.34 (95% CI = 1.23-1.45, p < .00001; Q-test p = .64, I-squared = 0%). The HR for DFS was 1.48 (95% CI = 1.18-1.86, p = .0007; Q-test p = .31, I-squared = 16%), and the HR for DSS was 1.66 (95% CI = 1.5-2.19, p = .0004; Q-test p = .96, I-squared = 0%). The odds ratio for PCs was 3.33 (95% CI = 2.10-5.29, p < .00001; Q-test p = .14, I-squared = 42%). This meta-analysis showed a significant association between transfusions and OS, DFS, DSS and PCs. The quality of the evidence was low. Aggregation, selection and selective reporting bias were detected. The biases shifted the results towards significance. Further studies using accurate adjustment methods are needed. Until such additional studies are performed, caution in administering transfusions and optimization of cancer patient blood management are warranted.
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Multimodal Prehabilitation Programs as a Bundle of Care in Gastrointestinal Cancer Surgery: A Systematic Review. Dis Colon Rectum 2018; 61:124-138. [PMID: 29219922 DOI: 10.1097/dcr.0000000000000987] [Citation(s) in RCA: 98] [Impact Index Per Article: 14.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
BACKGROUND Prehabilitation reflects a proactive process of preoperative optimization undertaken between cancer diagnosis and definitive surgical treatment, with the intent of improving physiological capacity to withstand the major insult of surgery. Prehabilitation before GI cancer surgery is currently not widely adopted, and most research has focused on unimodal interventions such as exercise therapy, nutritional supplementation, and hematinic optimization. A review of the existing literature was undertaken to investigate the impact of multimodal prehabilitation programs as a "bundle of care." DATA SOURCE A systematic literature search was performed utilizing Medline, PubMed, Embase, Cinahl, Cochrane, and Google Scholar databases. STUDY SELECTION The quality of studies was assessed by using the Cochrane tool for assessing risk of bias (randomized trials) and the Newcastle-Ottawa Quality Assessment scale (cohort studies). INTERVENTION Studies were chosen that involved pre-operative optimization of patients before GI cancer surgery. MAIN OUTCOMES The primary outcome measured was the impact of prehabilitation programs on preoperative fitness and postoperative outcomes. RESULTS Of the 544 studies identified, 20 were included in the qualitative analysis. Two trials investigated the impact of multimodal prehabilitation (exercise, nutritional supplementation, anxiety management). Trials exploring prehabilitation with unimodal interventions included impact of exercise therapy (7 trials), impact of preoperative iron replacement (5 trials), nutritional optimization (5 trials), and impact of preoperative smoking cessation (2 trials). Compliance within the identified studies was variable (range: 16%-100%). LIMITATIONS There is a lack of adequately powered trials that utilize objective risk stratification and uniform end points. As such, a meta-analysis was not performed because of the heterogeneity in study design. CONCLUSION Although small studies are supportive of multimodal interventions, there are insufficient data to make a conclusion about the integration of prehabilitation in GI cancer surgery as a bundle of care. Larger, prospective trials, utilizing uniform objective risk stratification and structured interventions, with predefined clinical and health economic end points, are required before definitive value can be assigned to prehabilitation programs.
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Wilson MJ, Dekker JW, Bruns E, Borstlap W, Jeekel J, Zwaginga JJ, Schipperus M. Short-term effect of preoperative intravenous iron therapy in colorectal cancer patients with anemia: results of a cohort study. Transfusion 2017; 58:795-803. [PMID: 29250797 DOI: 10.1111/trf.14456] [Citation(s) in RCA: 27] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/18/2017] [Revised: 09/18/2017] [Accepted: 11/06/2017] [Indexed: 01/28/2023]
Abstract
BACKGROUND In the treatment of preoperative anemia, which is associated with increased postoperative morbidity, iron supplementation can replace blood transfusion and erythropoiesis-stimulating agents. The aim of this study was to assess the efficacy of preoperative intravenous (IV) iron infusion in optimizing hemoglobin (Hb) levels in anemic colorectal cancer patients. STUDY DESIGN AND METHODS A retrospective cohort study was performed on patients who underwent surgery for colorectal cancer between 2010 and 2016 in a single teaching hospital. The primary outcome measure, the change in Hb level, was assessed by comparing anemic patients receiving usual care (UC; i.e. no iron therapy and no blood transfusion) with anemic patients receiving IV iron therapy (no blood transfusion). RESULTS A total of 758 patients with colorectal cancer were eligible, of whom 318 (41.9%) had anemia. The IV and the UC groups included 52 and 153 patients with mean Hb levels at diagnosis of 6.3 and 6.9 mmol/L, respectively. In the IV group, preoperative Hb level was significantly increased compared to the UC group (0.65 mmol/L vs. 0.10 mmol/L, p < 0.001). High increase in Hb level after iron infusion was associated with initial higher transferrin and lower ferritin levels (high vs. poor responders: median transferrin 2.9 g/L vs. 2.7 g/L, median ferritin 12 µg/L vs. 27 µg/L). CONCLUSION Implementation of IV iron therapy in anemic colorectal cancer patients leads to a distinct increase of preoperative Hb level. IV iron therapy is most effective in patients presenting with more severe anemia, and with higher transferrin and lower ferritin levels, markers for an absolute iron deficiency (ID), compared to functional ID.
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Affiliation(s)
- Michael Jordi Wilson
- TRIP Hemovigilance and Biovigilance Office, Leiden, the Netherlands.,Department of Surgery, Rotterdam, the Netherlands
| | - Jan Willem Dekker
- Department of Surgery, Reinier de Graaf Hospital, Delft, the Netherlands
| | - Emma Bruns
- Department of Surgery, Academic Medical Center, Amsterdam, the Netherlands
| | - Wernard Borstlap
- Department of Surgery, Academic Medical Center, Amsterdam, the Netherlands
| | - Johannes Jeekel
- Department of Neuroscience, Erasmus University Medical Center, Rotterdam, the Netherlands
| | - Jaap Jan Zwaginga
- Center for Clinical Transfusion Research, Sanquin Research, Leiden.,Department of Immunohematology and Blood Transfusion, Leiden University Medical Center, Leiden, the Netherlands
| | - Martin Schipperus
- TRIP Hemovigilance and Biovigilance Office, Leiden, the Netherlands.,Department of Hematology, Haga Teaching Hospital, the Hague, the Netherlands
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Wilson MJ, Harlaar JJ, Jeekel J, Schipperus M, Zwaginga JJ. Iron therapy as treatment of anemia: A potentially detrimental and hazardous strategy in colorectal cancer patients. Med Hypotheses 2017; 110:110-113. [PMID: 29317052 DOI: 10.1016/j.mehy.2017.12.011] [Citation(s) in RCA: 18] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/13/2017] [Revised: 11/21/2017] [Accepted: 12/03/2017] [Indexed: 01/22/2023]
Abstract
In colorectal cancer patients, iron therapy, and especially intravenous iron therapy, is increasingly used to treat anemia and reduce the use of blood transfusions. However, iron has also been shown to be an essential nutrient for rapidly proliferating tissues and cells. In this respect, anemia of inflammation, characterized by limited duodenal iron uptake and sequestration of iron into the reticuloendothelial system, might be regarded as a potentially effective defense strategy of the human body against tumor growth. We therefore hypothesize that iron therapy, by supporting colorectal tumor growth and increasing the metastatic potential, may worsen tumor prognosis in colorectal cancer patients. This hypothesis is particularly supported for colorectal cancer by laboratory, epidemiological and animal studies, demonstrating the role of iron in all aspects of tumor development growth. Compared to non-malignant colon cells, tumor cells differ in the levels and activity of many iron import and export proteins, resulting in an increase in intracellular iron level and enhanced proliferation. In addition, it is demonstrated that iron is able to amplify Wnt signaling in tumors with Apc mutation, a critical mutation in the development of colorectal cancer. If our hypothesis is to be confirmed, current practice of iron administration, as treatment for anemia and as replacement of blood transfusions, can be hazardous and should be completely reconsidered.
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Affiliation(s)
- M J Wilson
- TRIP Hemovigilance and Biovigilance Office, Leiden, The Netherlands; Erasmus University Medical Center Rotterdam, Department of Surgery, The Netherlands.
| | - J J Harlaar
- VU Medical Center Amsterdam, Department of Surgery, The Netherlands
| | - J Jeekel
- Erasmus University Medical Center Rotterdam, Department of Neuroscience, The Netherlands
| | - M Schipperus
- TRIP Hemovigilance and Biovigilance Office, Leiden, The Netherlands; Haga Teaching Hospital the Hague, Department of Hematology, The Netherlands
| | - J J Zwaginga
- Center for Clinical Transfusion Research, Sanquin Research, Leiden, The Netherlands; Leiden University Medical Center, Department of Immunohematology and Blood Transfusion, The Netherlands
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Cappellini MD, Comin-Colet J, de Francisco A, Dignass A, Doehner W, Lam CS, Macdougall IC, Rogler G, Camaschella C, Kadir R, Kassebaum NJ, Spahn DR, Taher AT, Musallam KM. Iron deficiency across chronic inflammatory conditions: International expert opinion on definition, diagnosis, and management. Am J Hematol 2017; 92:1068-1078. [PMID: 28612425 PMCID: PMC5599965 DOI: 10.1002/ajh.24820] [Citation(s) in RCA: 314] [Impact Index Per Article: 39.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/12/2017] [Revised: 06/01/2017] [Accepted: 06/05/2017] [Indexed: 12/11/2022]
Abstract
Iron deficiency, even in the absence of anemia, can be debilitating, and exacerbate any underlying chronic disease, leading to increased morbidity and mortality. Iron deficiency is frequently concomitant with chronic inflammatory disease; however, iron deficiency treatment is often overlooked, partially due to the heterogeneity among clinical practice guidelines. In the absence of consistent guidance across chronic heart failure, chronic kidney disease and inflammatory bowel disease, we provide practical recommendations for iron deficiency to treating physicians: definition, diagnosis, and disease‐specific diagnostic algorithms. These recommendations should facilitate appropriate diagnosis and treatment of iron deficiency to improve quality of life and clinical outcomes.
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Affiliation(s)
- Maria Domenica Cappellini
- Rare Diseases Centre; Department of Medicine and Medical Specialties, Fondazione IRCCS Ca'Granda-Ospedale Maggiore Policlinico; Milan Italy
- Department of Clinical Sciences and Community Health; Università degli Studi di Milano; Milan Italy
| | - Josep Comin-Colet
- Community Heart Failure Program; Department of Cardiology, Bellvitge University Hospital, University of Barcelona and Biomedical Research Institut (IDIBELL), Hospitalet de Liobregat; Barcelona Spain
| | - Angel de Francisco
- Department of Nephrology; Valdecilla Universitario Hospital, University of Cantabria; Santander Spain
| | - Axel Dignass
- Department of Medicine I; Agaplesion Markus Hospital; Frankfurt Germany
| | - Wolfram Doehner
- Center for Stroke Research CSB and Department of Cardiology; Virchow Campus, Charité Universitätsmedizin Berlin; Berlin Germany
| | - Carolyn S. Lam
- Department of Cardiology; National Heart Centre Singapore and Duke-NUS Medical School; Singapore
| | - Iain C. Macdougall
- Department of Renal Medicine; King's College Hospital; London United Kingdom
| | - Gerhard Rogler
- Division of Gastroenterology and Hepatology; University of Zurich; Zurich Switzerland
| | - Clara Camaschella
- Division of Genetics and Cell Biology; San Raffaele Scientific Institute and Vita-Salute University; Milan Italy
| | - Rezan Kadir
- Department of Obstetrics & Gynaecology; Royal Free Foundation Hospital and University College Hospital; London United Kingdom
| | - Nicholas J. Kassebaum
- Institute for Health Metrics and Evaluation, University of Washington; Seattle Washington, DC
- Department of Anesthesiology and Pain Medicine; Seattle Children's Hospital, University of Washington; Seattle Washington, DC
| | - Donat R. Spahn
- Institute of Anaesthesiology, University of Zurich and University Hospital Zurich; Zurich Switzerland
| | - Ali T. Taher
- Department of Internal Medicine; American University of Beirut Medical Center; Beirut Lebanon
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Wilson MJ, Dekker JWT, Harlaar JJ, Jeekel J, Schipperus M, Zwaginga JJ. The role of preoperative iron deficiency in colorectal cancer patients: prevalence and treatment. Int J Colorectal Dis 2017; 32:1617-1624. [PMID: 28889320 PMCID: PMC5635103 DOI: 10.1007/s00384-017-2898-1] [Citation(s) in RCA: 43] [Impact Index Per Article: 5.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 08/30/2017] [Indexed: 02/04/2023]
Abstract
BACKGROUND In preoperative blood management of colorectal cancer patients, intravenous iron therapy is increasingly used to treat anaemia and prevent red blood cell transfusions. However, while iron deficiency is the most common cause of anaemia, little is known about the prevalence and namely type of iron deficiency in this population, whereas both types of iron deficiency (i.e. absolute and functional iron deficiency) are recommended to be treated differently by international cancer guidelines. OBJECTIVE The aim of present study is to investigate the prevalence and namely type of iron deficiency in colorectal cancer patients, and to assess its clinical relevance. METHODS Preoperative iron status, clinical parameters (i.e. age, ASA classification, tumour location, tumour stage) and postoperative complications were retrospectively collected for all newly diagnosed colorectal cancer patients in our institution over a 3-year period. RESULTS Iron deficiency was observed in 163 (48.1%) of 339 patients. Of these iron-deficient patients, 3.7% had an isolated absolute iron deficiency (AID) and 15.3% a functional iron deficiency (FID), while the rest had a combination of AID and FID. Anaemia was present in 66.1% of iron-deficient patients. Iron deficiency was significantly associated with an increased postoperative complication rate (univariable OR 1.94, p = 0.03, multivariable OR 1.84, p = 0.07), with right-sided tumours (p < 0.001), high ASA classification (p = 0.002), advanced tumour stage (p = 0.01) and advanced age (p = 0.04). In comparing clinical parameters between patients with AID and FID, advanced age was significantly associated with FID (p = 0.03), and the presence of anaemia with AID (p = 0.02). CONCLUSION In preoperative colorectal cancer patients, there is a high prevalence of iron deficiency, including a high percentage of patients with-a component of-functional iron deficiency, associated with the increased postoperative complication rate. As both types of iron deficiency require a different treatment strategy, our results illustrate the therapeutic potential of especially intravenous iron supplementation in patients with severe iron deficiency and stress the urgency of routinely monitoring preoperative iron status and differentiation between types of iron deficiency. As iron therapy may also be potentially harmful in respect to stimulation of tumour growth, future clinical trials assessing the long-term effect of iron therapy are necessary.
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Affiliation(s)
- M J Wilson
- TRIP Hemovigilance and Biovigilance Office, Leiden, the Netherlands.
- Department of Surgery, Erasmus University Medical Center Rotterdam, Rotterdam, the Netherlands.
| | - J W T Dekker
- Department of Surgery, Reinier de Graaf Hospital, Delft, the Netherlands
| | - J J Harlaar
- Department of Surgery, Westfriesgasthuis Hoorn, Hoorn, the Netherlands
- Department of Surgery, VU Medical Center Amsterdam, Amsterdam, the Netherlands
| | - J Jeekel
- Department of Neuroscience, Erasmus University Medical Center Rotterdam, Rotterdam, the Netherlands
| | - M Schipperus
- TRIP Hemovigilance and Biovigilance Office, Leiden, the Netherlands
- Department of Hematology, Haga Teaching Hospital, The Hague, the Netherlands
| | - J J Zwaginga
- Sanquin Research, Center for Clinical Transfusion Research, Leiden, the Netherlands
- Department of Immunohematology and Blood Transfusion, Leiden University Medical Center, Leiden, the Netherlands
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Stein J, Connor S, Virgin G, Ong DEH, Pereyra L. Anemia and iron deficiency in gastrointestinal and liver conditions. World J Gastroenterol 2016; 22:7908-7925. [PMID: 27672287 PMCID: PMC5028806 DOI: 10.3748/wjg.v22.i35.7908] [Citation(s) in RCA: 67] [Impact Index Per Article: 7.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/06/2016] [Revised: 07/18/2016] [Accepted: 08/10/2016] [Indexed: 02/06/2023] Open
Abstract
Iron deficiency anemia (IDA) is associated with a number of pathological gastrointestinal conditions other than inflammatory bowel disease, and also with liver disorders. Different factors such as chronic bleeding, malabsorption and inflammation may contribute to IDA. Although patients with symptoms of anemia are frequently referred to gastroenterologists, the approach to diagnosis and selection of treatment as well as follow-up measures is not standardized and suboptimal. Iron deficiency, even without anemia, can substantially impact physical and cognitive function and reduce quality of life. Therefore, regular iron status assessment and awareness of the clinical consequences of impaired iron status are critical. While the range of options for treatment of IDA is increasing due to the availability of effective and well-tolerated parenteral iron preparations, a comprehensive overview of IDA and its therapy in patients with gastrointestinal conditions is currently lacking. Furthermore, definitions and assessment of iron status lack harmonization and there is a paucity of expert guidelines on this topic. This review summarizes current thinking concerning IDA as a common co-morbidity in specific gastrointestinal and liver disorders, and thus encourages a more unified treatment approach to anemia and iron deficiency, while offering gastroenterologists guidance on treatment options for IDA in everyday clinical practice.
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Chang CC, Sun JT, Chen JY, Chen YT, Li PY, Lee TC, Su MJ, Wu JM, Yen TH, Chu FY. Impact of Peri-Operative Anemia and Blood Transfusions in Patients with Gastric Cancer Receiving Gastrectomy. Asian Pac J Cancer Prev 2016; 17:1427-1431. [PMID: 27039784 DOI: 10.7314/apjcp.2016.17.3.1427] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/10/2022] Open
Abstract
BACKGROUND Potential disadvantages of blood transfusion during curative gastrectomy for gastric cancer have been reported, and the role of peri-operative transfusions remains to be ascertained. Thus, the aim of our study was to survey its impact in patients with gastric cancer undergoinging gastrectomy. MATERIALS AND METHODS Clinical data of patients receiving curative gastrectomy at Far Eastern Memorial Hospital were obtained. Findings for pre-operative anemia states, pre-, peri- and post-operative transfusion of red blood cell (RBC) products as well as post-operative complication events were collected for univariate analysis. RESULTS A total of 116 patients with gastric cancer received gastrectomy at Far Eastern Memorial Hospital from 2011 to 2014. Both pre-operative and intra- and post-operative transfusion of RBC products were markedly associated with post-operative infectious events (OR: 3.70, 95% CI: 1.43-9.58, P=0.002; OR: 8.20, 95% CI: 3.11-22.62, P<0.001, respectively). In addition, peri- and post-operative RBC transfusion was significantly associated with prolonged hospital stay from admission to discharge (OR: 8.66, 95% CI: 1.73-83.00, P=0.002) and post-operative acute renal failure (OR: 19.69, 95% CI: 2.66-854.56, P<0.001). Also, the overall survival was seemingly decreased by peri-operative RBC transfusion in our gastric cancer cases (P=0.078). CONCLUSIONS Our survey indicated that peri-operative RBC transfusion could increase the risk of infectious events and acute renal failure post curative gastrectomy as well as worsen the overall survival in gastric cancer cases. Hence, unnecessary blood transfusion before, during and after curative gastrectomy should be avoided in patients with gastric cancer.
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Affiliation(s)
- Chih-Chun Chang
- Department of Clinical Pathology, Far Eastern Memorial Hospital, New Taipei, Taiwan E-mail :
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Borstlap WAA, Buskens CJ, Tytgat KMAJ, Tuynman JB, Consten ECJ, Tolboom RC, Heuff G, van Geloven AAW, van Wagensveld BA, Wientjes CACA, Gerhards MF, de Castro SMM, Jansen J, van der Ven AWH, van der Zaag E, Omloo JM, van Westreenen HL, Winter DC, Kennelly RP, Dijkgraaf MGW, Tanis PJ, Bemelman WA. Erratum to: Multicentre randomized controlled trial comparing ferric(III) carboxymaltose infusion with oral iron supplementation in the treatment of preoperative anaemia in colorectal cancer patients. BMC Surg 2015; 15:110. [PMID: 26450558 PMCID: PMC4599035 DOI: 10.1186/s12893-015-0090-5] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/07/2015] [Accepted: 09/07/2015] [Indexed: 01/22/2023] Open
Affiliation(s)
- W A A Borstlap
- Department of Surgery, Academic Medical Centre, University of Amsterdam, Amsterdam, The Netherlands.
| | - C J Buskens
- Department of Surgery, Academic Medical Centre, University of Amsterdam, Amsterdam, The Netherlands
| | - K M A J Tytgat
- Department of Gastroenterology, Academic Medical Centre, University of Amsterdam, Amsterdam, The Netherlands
| | - J B Tuynman
- Department of Surgery, VU University Medical Centre, Amsterdam, The Netherlands
| | - E C J Consten
- Department of Surgery, Meander Medical Centre, Amersfoort, The Netherlands
| | - R C Tolboom
- Department of Surgery, Meander Medical Centre, Amersfoort, The Netherlands
| | - G Heuff
- Department of Surgery, Borstlap et al. BMC Surgery (2015) 15:78 Spaarne Hospital, Hoofddorp, The Netherlands
| | | | - B A van Wagensveld
- Department of Surgery, Sint Lucas Andreas Hospital, Amsterdam, The Netherlands
| | - C A C A Wientjes
- Department of Gastroenterology, Sint Lucas Andreas Hospital, Amsterdam, The Netherlands
| | - M F Gerhards
- Department of Surgery, Onze Lieve Vrouwe Gasthuis, Amsterdam, The Netherlands
| | - S M M de Castro
- Department of Surgery, Onze Lieve Vrouwe Gasthuis, Amsterdam, The Netherlands
| | - J Jansen
- Department of Gastroenterology, Onze Lieve Vrouwe Gasthuis, Amsterdam, The Netherlands
| | | | - E van der Zaag
- Department of Surgery, Gelre Hospital, Apeldoorn, The Netherlands
| | - J M Omloo
- Department of Surgery, Gelre Hospital, Apeldoorn, The Netherlands
| | | | - D C Winter
- Department of Surgery, St. Vincent's Hospital, Dublin, Ireland
| | - R P Kennelly
- Department of Surgery, St. Vincent's Hospital, Dublin, Ireland
| | - M G W Dijkgraaf
- Clinical Research Unit, Academic Medical Centre, University of Amsterdam, Amsterdam, The Netherlands
| | - P J Tanis
- Department of Surgery, Academic Medical Centre, University of Amsterdam, Amsterdam, The Netherlands
| | - W A Bemelman
- Department of Surgery, Academic Medical Centre, University of Amsterdam, Amsterdam, The Netherlands
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