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ORIGINAL ARTICLE
Year : 2022  |  Volume : 25  |  Issue : 7  |  Page : 1102-1106

Does preoperative anaemia have an effect on the perioperative period in colorectal cancer surgery?


University of Health Science, Istanbul Kartal Dr. Lutfi Kirdar City Hospital, General Surgery Clinic, Istanbul, Turkey

Date of Submission09-Jul-2021
Date of Acceptance06-May-2022
Date of Web Publication20-Jul-2022

Correspondence Address:
Dr. M M Altintas
University of Health Science, Istanbul Kartal Dr. Lutfi Kirdar City Hospital, General Surgery Clinic, Istanbul
Turkey
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/njcp.njcp_1664_21

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   Abstract 


Background: Colorectal cancer (CRC) is the second most frequently diagnosed cancer in women and the third in men. Anaemia is a common condition in patients with CRC. Aim: In this study, we aimed to retrospectively analyse the relationship between preoperative anaemia (POA) and postoperative complications in patients with colorectal cancer (CRC) that underwent elective surgery. Patients and Methods: The data of patients who underwent elective curative surgery for CRC between January 2015 and December 2020 and had pathologically-proven cancer were evaluated retrospectively. We examined the effect of demographic characteristics of patients, preoperative haemoglobin, cancer localization (colon/rectum), American Society of Anaesthesiologist (ASA) classification, preoperative co-morbidity, surgical method (laparoscopic/open), stoma status, tumor stage, presence of preoperative anaemia on surgical site infection, pulmonary complications, renal complications, anastomotic leaks, and need for intensive care and re-operation in the postoperative period. Results: Of the 352 patients who underwent curative resection for CRC, 177 (50.3%) were diagnosed with POA. The median haemoglobin value was 10.7 g/dl in POA patients while it was 13.6 g/dl in the non-POA group. Regarding the localization of tumor, the patients with tumors on the right colon were more statistically significant in terms of POA (p < 0.05). Patients with POA had a higher rate of hypertension and coronary artery disease compared to patients without POA (p < 0.05). In patients with POA, surgical site infection and need for intensive care were statistically significant in the postoperative period compared to patients without POA (p < 0.05, P < 0.01, respectively). However, there was no significant difference between the two groups regarding pulmonary complications, renal complications, anastomotic leaks, and need for re-operation in the postoperative period. Conclusion: We believe that POA should be corrected prior to surgery to reduce not only the need for intensive care but also surgical site infection in patients undergoing elective curative surgery for CRC.

Keywords: Blood transfusion, colorectal cancer, preoperative anaemia


How to cite this article:
Altintas M M, Kaya S, Kocaoglu A E, Mulkut F. Does preoperative anaemia have an effect on the perioperative period in colorectal cancer surgery?. Niger J Clin Pract 2022;25:1102-6

How to cite this URL:
Altintas M M, Kaya S, Kocaoglu A E, Mulkut F. Does preoperative anaemia have an effect on the perioperative period in colorectal cancer surgery?. Niger J Clin Pract [serial online] 2022 [cited 2022 Aug 19];25:1102-6. Available from: https://www.njcponline.com/text.asp?2022/25/7/1102/351455




   Introduction Top


Colorectal cancer (CRC) is the second most frequently diagnosed cancer in women and the third in men, causing more than 1.4 million new cases and approximately 694,000 deaths worldwide each year.[1] Anaemia is a common condition in patients with CRC. The rate of anaemia is 40% in patients with early stage CRC and 80% in patients with advanced stage CRC.[2] Studies have shown that anaemia and many factors related to the patient and the disease are associated with increased postoperative morbidity and mortality.[3],[4] Anaemia is a decrease in circulating red blood cell count or circulating haemoglobin concentration.[5] There are several studies reporting association between anaemia and adverse postoperative outcomes. On the other hand, discussions regarding the treatment of POA are going on. As a matter of fact, although there is no conclusive evidence, it is thought that iron therapy may worsen the prognosis of CRC by triggering tumor growth and increasing the metastasis potential. Nevertheless, to this end, it is recommended to use iron therapy to correct POA and reduce the need for blood transfusion.[6] Iron replacement therapies, such as oral iron therapy, are associated with harmful side effects including abdominal pain, constipation, and diarrhoea. It has been reported that the rates of non-compliance with treatment attributed to such side effects are around 40%.[7]

Additionally, absorption pathways and access to oral iron supplementation may be impaired in patients with malignancies.[8] New iron preparations for intravenous application have been developed that are recommended for safer, better tolerated and more effective treatment of iron deficiency anaemia.[9],[10] Contrary to studies recommending the use of iron preparations in POA, another study reported that iron preparations would be too slow to treat anaemia and the treatment might even last more than one year in some patients.[11] Moreover, most CRC patients will need adjuvant therapy after surgery. To start chemotherapy, a haemoglobin value greater than 9 g/dl is requested.[11] For these reasons, RBC transfusion is applied to correct anaemia in patients with CRC. It was reported in a meta-analysis that POA caused a 2.9-fold increase in postoperative mortality, a 3.75-fold increase in the risk of acute renal failure, and a 1.93-fold increase in postoperative infection risk in major surgeries.[12] POA increases postoperative mortality in cardiac, orthopaedic, gastric, and oesophageal surgery.[12] However, there is not adequate data on whether POA is a risk factor for complications that may develop after elective CRC surgery. In this study, we aimed to retrospectively analyse the relationship between POA and postoperative complications in patients with CRC that underwent elective surgery.


   Patients and Methods Top


The data of patients who underwent elective curative surgery for CRC between January 2015 and December 2020 and had pathologically proven cancer were evaluated retrospectively. This study was approved by our hospital's ethics committee with decision number 514/194/31 dated January 27, 2021 Patients with metastasis, a previous history of other organ malignancy, patients who could not undergo curative resection, patients with obstructed/perforated CRC who underwent emergency surgery, patients with systemic diseases (such as leukaemia, lymphoma), and those who had blood replacement 1 month before the surgery were excluded from the study. POA was defined as a haemoglobin level below 12 g/dl.[13] In line with our clinical protocol, patients were given intravenous ceftriaxone + metronidazole before the operation and antibiotherapy was maintained for 72 hours. If there were signs of infection in the postoperative clinical observation or laboratory examinations, the current treatment was extended or a different antibiotherapy was administered depending on the recommendation of the infectious diseases specialist. All patients underwent mechanical bowel preparation before surgery. Curative resection was performed in all patients in accordance with oncological principles (lymph node dissection, total mesocolic/mesorectal excision, R0 resection). Either laparoscopic or open surgery was performed depending on the surgeon's preference. Again, depending on the surgeon's preference, a protective stoma was opened. All surgeries were performed by colorectal surgeons. We examined the effect of demographic characteristics of patients, preoperative haemoglobin, cancer localization (colon/rectum), American Society of Anaesthesiologist (ASA) classification, preoperative co-morbidity, surgical method (laparoscopic/open), stoma status, tumor stage, presence of preoperative anaemia on surgical site infection, pulmonary complications, renal complications, anastomotic leaks, and need for intensive care and re-operation in the postoperative period.

Statistical analysis

Statistical analysis was performed with the Statistical Package for Social Sciences (SPSS) for Windows 20.0. Data were summarized in average ± standard deviation, numbers (n) and percentages (%). Categorical variables were compared using the Chi-square test or the Fisher's exact test. All statistical calculations were two-way and P < 0.05 was considered statistically significance at the 95% confidence interval.


   Results Top


Of the 352 patients who underwent curative resection for CRC, 177 (50.3%) were diagnosed with POA. No significant difference was detected between the two groups regarding gender and age. The median haemoglobin value was 10.7 (6.1-11.9) g/dl in POA patients while it was 13.6 (12-18) g/dl in the non-POA group. In the POA group, an average of 2.9 (2-4) units of blood was transfused to 56 (31.6%) patients with a haemoglobin value below 10 g/dl in the preoperative period. Regarding the localization of tumor, the patients with tumors on the right colon were more statistically significant in terms of POA (p < 0.05). There was no significant difference between the two groups in terms of ASA score, presence of ostomy and tumor stage. However, it was observed that conventional approach rather than laparoscopic surgery was preferred for patients with POA (p < 0.05) [Table 1]. Patients with POA had a higher rate of hypertension and coronary artery disease compared to patients without POA (p < 0.05) [Table 2]. In patients with POA, surgical site infection and need for intensive care were statistically significant in the postoperative period compared to patients without POA (p < 0.05, P < 0.01, respectively). However, there was no significant difference between the two groups regarding pulmonary complications, renal complications, anastomotic leaks, and need for re-operation in the postoperative period [Table 3].
Table 1: Demographic and clinical characteristics of patients

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Table 2: Patients' Comorbidities

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Table 3: Patients' postoperative complications

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   Discussion Top


CRC is often associated with anaemia, and it has been reported that approximately 40% of newly diagnosed cases are anaemic and that the incidence of anaemia is higher in patients with advanced CRC.[14] The cause of such anaemia is generally iron deficiency secondary to chronic blood loss or iron deficiency due to impaired utilization of iron stores following iron sequestration and functional iron deficiency.[10],[15] Anaemia has been shown to be a risk factor for postoperative complications and extended hospital stays in CRC patients.[16] POA is associated with postoperative complications and particularly with surgical wound site infection after major surgeries.[8],[17]

Anaemia is closely associated with deterioration in long-term disease-free survival and overall survival in cancer patients.[18] However, there is not enough data in the literature regarding the effects of POA after CRC surgery. Our study aimed to retrospectively analyse the relationship between POA and postoperative complications in patients with CRC that underwent elective surgery. More than half of patients with CRC are anaemic on their first admission to hospital, and two-thirds of them have moderate to severe anaemia.

There are various factors that play a role in the formation of anaemia in patients with CRC. Chronic blood loss and the resulting iron deficiency are the most significant factors for anaemia.[16] Other factors include advanced age, gender, and localization, size and grade of the tumor. Patients with colon cancer present with higher rate of POA than patients with rectal cancer. In our study, half of our patients were anaemic, which is consistent with the literature. However, we did not identify a statistically significant difference in the incidence of anaemia for age, gender and advanced grade.

Additionally, in our study, conventional surgery was preferred over laparoscopic surgery in patients with POA. It may take too much time, even more than a year, to cure anaemia with iron preparations in some patients. Moreover, most CRC patients will need adjuvant therapy after surgery. To start chemotherapy, a haemoglobin value greater than 9 g/dL[11] is requested. For these reasons, RBC transfusion is applied to correct anaemia in patients with CRC. There are only a few studies addressing possible long-term effects of iron preparations including disease-free survival and overall survival rather than short-term effects aiming to increase haemoglobin levels in patients with colorectal cancer. Since anaemia of inflammation is considered a natural defence mechanism of the human body triggered to slow the growth of tumor cells, these long-term effects of iron preparations are of interest.[19]

The rate of POA is higher in patients with cancer in the proximal colon than in patients with cancer in the distal colon and rectum.[20] In Dunne et al.,[21] the authors reported the rate of POA to be 47% of tumors located in the right colon, 34% in tumors located in the left colon, and 19% in tumors of the rectum. In our study, POA was found to be statistically significant only in patients with colon cancer located in the right colon compared to patients who were non-anaemic.

Although studies provide information about the negative effects of POA in the postoperative period,[12],[22] it does still remain unclear. Experimental studies have proven that due to anaemia, there is a decrease in the distribution of oxygen carried to the organs leading to the development of organ dysfunction as a result of hypoxia of organs, especially the brain and the kidneys.[23],[24],[25] In our study, the patients with POA had a higher rate of hypertension and coronary artery disease compared to those without POA. It has been reported that there is an increase in postoperative surgical site infections due to acute kidney injury and impaired tissue oxygenation caused by anaemia.[12],[25] In Liu et al., the rate of surgical site infection was found to be 2.44 times higher in CRC patients with POA as compared to non-anaemic patients. However, Liu et al.[13] stated that there was no relation between POA and anastomotic leak. This study indicated that surgical site infection and need for intensive care were statistically significant in the postoperative period in patients with POA compared to those without POA (p < 0.05, P < 0.01, respectively). However, there was no significant difference between the two groups regarding pulmonary complications, renal complications, anastomotic leaks, and need for re-operation in the postoperative period.

In conclusion, we may interpret from the results of this study that POA should be corrected prior to surgery to reduce not only the need for intensive care but also surgical site infection in the perioperative period in patients undergoing elective curative surgery for CRC.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
   References Top

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Gustafsson UO, Scott MJ, Hubner M, Nygren J, Demartines N, Francis N, et al. Guidelines for perioperative care in elective colorectal surgery: Enhanced Recovery After Surgery Society recommendations. World J Surg 2018;43:659-95.  Back to cited text no. 8
    
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Bernard AC, Davenport DL, Chang PK, Vaughan TB, Zwischenberger JB. Intraoperative transfusion of 1 U to 2 U packed red blood cells is associated with increased 30-day mortality, surgical-site infection, pneumonia, and sepsis in general surgery patients. J Am Coll Surg 2009;208:931-7, 937e1-2; discussion 938-9.  Back to cited text no. 9
    
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Keeler BD, Simpson JA, Ng O, Padmanabhan H, Brookes MJ, Acheson AG; IVICA Trial Group. Randomized clinical trial of preoperative oral versus intravenous iron in anaemic patients with colorectal cancer. Br J Surg 2017;104:214-21.  Back to cited text no. 10
    
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Fowler AJ, Ahmad T, Phull MK, Allard S, Gillies MA, Pearse RM. Meta-analysis of the association between preoperative anaemia and mortality after surgery. Br J Surg 2015;102:1314-24.  Back to cited text no. 12
    
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Liu L, Liu L, Liang LC, Zhu ZQ, Wan X, Dai HB, et al. Impact of preoperative anemia on perioperative outcomes in patients undergoing elective colorectal surgery. Gastroenterol Res Pract 2018;2018:2417028.  Back to cited text no. 13
    
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Shander A, Van Aken H, Colomina MJ, Gombotz H, Hofmann A, Krauspe R, et al. Patient blood management in Europe. Br J Anaesth 2012;109:55-68.  Back to cited text no. 14
    
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Acheson AG, Brookes MJ, Spahn DR. Effects of allogeneic red blood cell transfusions on clinical outcomes in patients undergoing colorectal cancer surgery: A systematic review and meta-analysis. Ann Surg 2012;256:235-44.  Back to cited text no. 15
    
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Ristescu I, Pintilie G, Filip D, Jitca M, Fecheta R, Florescu I, et al. Perioperative anemia and transfusion in colorectal cancer patients. Chirurgia (Bucur) 2019;114:234-42.  Back to cited text no. 16
    
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Greenky M, Gandhi K, Pulido L, Restrepo C, Parvizi J. Preoperative anemia in total joint arthroplasty: Is it associated with periprosthetic joint infection? Clin Orthop Relat Res 2012;470:2695-701.  Back to cited text no. 17
    
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Wilson MJ, van Haaren M, Harlaar JJ, Park HC, Bonjer HJ, Jeekel J, et al. Long-term prognostic value of preoperative anemia in patients with colorectal cancer: A systematic review and metaanalysis. Surg Oncol 2017;26:96-104.  Back to cited text no. 18
    
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Toby R, Ravishankar RB, Ben C, Anna B, Sandy A, Marisa C, et al. Preoperative intravenous iron to treat anaemia before major abdominal surgery: A randomised, double-blind, controlled trial. Lancet 2020;396:1353-61.  Back to cited text no. 19
    
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Väyrynen JP, Tuomisto A, Väyrynen SA, Klintrup K, Karhu T, Mäkelä J, et al. Preoperative anemia in colorectal cancer: Relationships with tumor characteristics, systemic inflammation, and survival. Sci Rep 2018;8:1126.  Back to cited text no. 20
    
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Dunne JR, Gannon CJ, Osborn TM, Taylor MD, Malone DL, Napolitano LM. Preoperative anemia in colon cancer: Assessment of risk factors. Am Surg 2002;68:582-7.  Back to cited text no. 21
    
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Cladellas M, Bruguera J, Comín J, Vila J, de Jaime E, Martí J, et al. Is pre-operative anaemia a risk marker for in-hospital mortality and morbidity after valve replacement? Eur Heart J 2006;27:1093-9.  Back to cited text no. 22
    
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Li M, Bertout JA, Ratcliffe SJ, Eckenhoff MF, Simon MC, Floyd TF. Acute anemia elicits cognitive dysfunction and evidence of cerebral cellular hypoxia in older rats with systemic hypertension. Anesthesiology 2010;113:845-58.  Back to cited text no. 23
    
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Darby PJ, Kim N, Hare GM, Tsui A, Wang Z, Harrington A, et al. Anemia increases the risk of renal cortical and medullary hypoxia during cardiopulmonary bypass. Perfusion 2013;28:504-11.  Back to cited text no. 24
    
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Pierre YH, Maxime D, Jean J, Carla C, Emmanuel D, Gregory H. Impact of preoperative anemia on outcomes of enhanced recovery program after colorectal surgery: A monocentric retrospective study. World J Surg 2021;45:2326-36.  Back to cited text no. 25
    



 
 
    Tables

  [Table 1], [Table 2], [Table 3]



 

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