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World J Gastroenterol. Feb 28, 2008; 14(8): 1248–1251.
Published online Feb 28, 2008. doi:  10.3748/wjg.14.1248
PMCID: PMC2690674

Pre-operative hypoalbuminemia is a major risk factor for postoperative complications following rectal cancer surgery

Abstract

AIM: To determine the relationship between pre-operative hypoalbuminemia and the development of complications following rectal cancer surgery, as well as postoperative bowel function and hospital stay.

METHODS: The medical records of 244 patients undergoing elective oncological resection for rectal adenocarcinoma at Siriraj Hospital during 2003 and 2006 were reviewed. The patients had pre-operative serum albumin assessment. Albumin less than 35 g/L was recognized as hypoalbuminemia. Postoperative outcomes, including mortality, complications, time to first bowel movement, time to first defecation, time to resumption of normal diet and length of hospital stay, were analyzed.

RESULTS: The patients were 139 males (57%) and 105 females (43%) with mean age of 62 years. Fifty-six patients (23%) had hypoalbuminemia. Hypoalbuminemic patients had a significantly larger tumor size and lower body mass index compared with non-hypoalbuminemic patients (5.5 vs 4.3 cm; P < 0.001 and 21.9 vs 23.2 kg/m2; P = 0.02, respectively). Thirty day postoperative mortality was 1.2%. Overall complication rate was 25%. Hypoalbuminemic patients had a significantly higher rate of postoperative complications (37.5% vs 21.3%; P = 0.014). In univariate analysis, hypoalbuminemia and ASA status were two risk factors for postoperative complications. In multivariate analysis, hypoalbuminemia was the only significant risk factor (odds ratio 2.22, 95% CI 1.17-4.23; P < 0.015). Hospitalization in hypoalbuminemic patients was significantly longer than that in non-hypoalbuminemic patients (13 vs 10 d, P = 0.034), but the parameters of postoperative bowel function were not significantly different between the two groups.

CONCLUSION: Pre-operative hypoalbuminemia is an independent risk factor for postoperative complications following rectal cancer surgery.

Keywords: Hypoalbuminemia, Rectal cancer, Outcomes, Morbidity, Postoperative bowel function

INTRODUCTION

Malnutrition is a common problem in gastrointestinal cancer patients that adversely affects surgical outcomes[13]. There are many tools to assess patients’ nutritional status. Serum albumin is a good and simple predictor of surgical risk and has a close correlation with the degree of malnutrition[4]. Hypoalbuminemia is a predictor of delayed recovery of bowel function and is strongly associated with postoperative complications after right hemicolectomy for right-sided colon cancer[5], or following other major gastrointestinal surgery[68]. However, there is little information regarding the effect of hypoalbuminemia on the development of postoperative complications after rectal cancer surgery, and the results remain controversial[911].

The aims of this study were to determine the relationship between pre-operative hypoalbuminemia and the development of complications following rectal cancer surgery, and to evaluate the effect of hypoalbuminemia on postoperative bowel function and hospital stay.

MATERIALS AND METHODS

Patients and data collection

After obtaining approval from the Institutional Ethics Committee, we carried out a retrospective analysis of patients undergoing elective oncological resection for rectal adenocarcinoma between January 2003 and December 2006 at the Department of Surgery, Faculty of Medicine Siriraj Hospital, Bangkok, Thailand. Rectal cancer was defined as a tumor with the lower edge located within 15 cm of the anal verge, as measured by rigid sigmoidoscopy. Patients were excluded if they had pelvic exenteration, or had had operations for recurrent tumors or acute complicated conditions such as colonic obstruction.

Each patient had a pre-operative serum albumin assessment. Serum albumin less than 35 g/L was recognized as hypoalbuminemia. Every patient underwent pre-operative mechanical bowel preparation. Standard oncological resection of the rectum was performed by either a laparoscopic or open approach. In case of sphincter-saving operation, colorectal anastomosis was performed without colonic pouch formation or protective stoma. In the case of abdominoperineal resection, primary closure of the perineal wound was performed after a pelvic drain had been placed. A nasogastric tube was inserted at the surgeon’s discretion.

Routine postoperative care was provided to each patient. Time to first bowel movement (passing flatus) was recorded by nursing staffs. The patients were allowed to have oral fluid if passing flatus. Resumption of a normal diet was decided by surgeons with patients’ compliance. Patients were discharged from the hospital if the drain was removed and they had no fever, good appetite and good ambulation. All patients were scheduled for follow-up at 30 d postoperatively.

Data recorded included patient demographic, tumor characteristics, operative details and postoperative outcomes. Patient-related factors included age, gender, American Society of Anesthesiologist (ASA) status, obesity (body mass index over 30 kg/m2), anemia (pre-operative hematocrit less than 30%), hypoalbuminemia and neoadjuvant chemoradiation. Tumor-related factors included location, size and TNM stage. Operation-related factors included the type of operation and requirement of blood transfusion. Postoperative outcomes, including mortality, complications, time to first bowel movement, time to first defecation, time to resumption of normal diet and length of hospital stay, were analyzed.

Statistical analysis

All data were prepared and analyzed using Statistical Package for the Social Sciences program version 11.0 for Windows (SPSS®, SPSS Inc., Chicago, IL). The Kolmogorov-Smirnov test was used to test for a normal pattern of data distribution. Unpaired t-tests were used to compare data between the two groups when they showed a normal distribution pattern. The Mann-Whitney U test was used when this was not the case. Pearson’s Chi-square test and Fisher’s exact test were used when the data were quantitative. Stepwise regression analysis was used for multivariate analysis in order to determine any confounding factors. A P-value of less than 0.05 was considered statistically significant.

RESULTS

Two hundred and forty four patients were studied. There were 139 males (57%) and 105 females (43%) with a mean age of 62 years (range 23-87). Fifty-six patients (23%) had hypoalbuminemia. Patients with hypoalbuminemia had a significantly larger size of the tumors and lower body mass index (BMI), compared with those without hypoalbuminemia (5.5 vs 4.3 cm; P < 0.001 and 21.9 vs 23.2 kg/m2; P = 0.02, respectively). Gender and tumor staging were not statistically different between the two groups (Table (Table11).

Table 1
Demographic data on non-hypoalbuminemic and hypoalbuminemic patients

Thirty day postoperative mortality was 1.2% (3 patients died; one massive pelvic hemorrhage, one perioperative myocardial infarction, and one anastomotic leakage with respiratory failure). Overall complication rate was 25%. Infectious complications were diagnosed in 59 patients (24%); 42 surgical site infections, 13 anastomotic leakage, 2 urinary tract infection and 2 pneumonia. Two patients (1%) developed noninfectious complications during hospitalization (one acute respiratory failure and one perioperative myocardial infarction). Hypoalbuminemic patients had a significantly higher rate of postoperative complication (37.5% vs 21.3%, P = 0.014).

Univariate analysis revealed hypoalbuminemia and ASA status as two risk factors for the development of postoperative complications (Table (Table2).2). In multivariate analysis, hypoalbuminemia was the only significant risk factor for postoperative complications (odds ratio 2.22, 95% CI 1.17-4.23; P < 0.015). Length of hospital stay in hypoalbuminemic patients was significantly longer than that in non-hypoalbuminemic patients (13.0 vs 10.4 d, P = 0.034), but time to first bowel movement, time to first defecation and time to resumption of normal diet were not significantly different between the two groups (Table (Table33).

Table 2
The relationship between the clinical characteristics of the patients and the development of postoperative complications analyzed using a univariate model
Table 3
Univariate analysis of clinical outcomes (mean ± SD)

DISCUSSION

Patients with rectal cancer are at risk of malnutrition due to cancer-induced higher metabolism, dietary intake reduction, and cancer cachexia[1214]. Tumor necrosis factor-alpha is considered to be the main mediator of cancer cachexia as it is responsible for different metabolic alterations and leads to impairment of hepatic protein synthesis[15]. Cancer patients also have increased whole protein turnover and subsequent body nitrogen loss[16]. Albumin has a long half-life of 20 d, so that metabolic effects on its concentration reflect prolonged malnourishment, as in cancer patients. Hypoalbuminemia is widely accepted to be a good indicator for malnutrition in many national cancer studies[7,11,17]. It is remarkable that tumor size, but not the stage, is relevant to hypoalbuminemia. The clear explanation of this association remains unknown. It is possible that large tumors cause more gastrointestinal symptoms, leading to poor intake and partial gut obstruction.

In this present study, univariate analysis showed that hypoalbuminemia and ASA status were significant risk factors for postoperative complications following rectal cancer surgery. However, hypoalbuminemia was the only independent factor for postoperative morbidity after multivariate analysis. Our finding is consistent with those of two large population-based prospective studies in France[7] and the United States[11]. Gibbs et al [11] reported that a decrease in serum albumin from concentrations greater than 46 g/L to less than 21 g/L was associated with an exponential increase in mortality rates from less than 1% to 29% and in morbidity rates from 10% to 65% following non-cardiac surgery. Moreover, hypoalbuminemia was a better predictor of some types of morbidity, especially sepsis and major infections. Ryan et al[18] showed decreased serum albumin concentration on the first postoperative day was also an independent predictor of poor surgical outcome following gastrointestinal cancer surgery.

Hypoalbuminemia was associated with poor tissue healing, decreased collagen synthesis in the surgical wounds or at the anastomosis[1921], and impairment of immune responses, such as macrophage activation and granuloma formation[22,23]. Therefore, in hypoalbuminemic patients, wound infection, remote infections such as pneumonia, and anastomotic leakage, were commonly found.

According to the present study, a tendency towards delayed recovery of postoperative bowel function has also been found in hypoalbuminemic patients, although this effect did not reach statistical significance. This may be because such patients develop more complications, including intra-abdominal sepsis, and because lower serum albumin causes swelling and edema of the intestine[24], resulting in paralytic ileus. Clearly, there would be other factors contributing to postoperative bowel function, such as narcotics administration and electrolyte status[2527]. Prolonged hospitalization in hypoalbuminemic patients may be the result of higher rates of postoperative complication and delayed bowel recovery.

With regard to the treatment of pre-existing hypoalbuminemia, no published studies have been able to demonstrate any advantage of albumin infusion on morbidity and mortality[28,29]. This may be because of insufficient albumin replacement or increased leakage of synthetic albumin into the extravascular spaces. However, a recent prospective randomized study reported the admini-stration of a supplemented diet before and after surgery was beneficial to outcomes in malnourished patients with gastrointestinal cancer[30].

In conclusion, pre-operative hypoalbuminemia is an independent risk factor for postoperative complications following rectal cancer surgery. Hypoalbuminemic patients also have a nonstatistically significant tendency to delayed recovery of postoperative bowel function. Low serum albumin may be used as a simple and low-cost prognostic tool to predict the risk of adverse surgical outcomes.

COMMENTS

Background

Malnutrition is a common problem in gastrointestinal cancer patients that adversely affects surgical outcomes. There are many tools to assess patients’ nutritional status. Serum albumin is a good and simple predictor of surgical risk and has a close correlation with the degree of malnutrition. Hypoalbuminemia is a predictor of delayed recovery of bowel function and is strongly associated with postoperative complications in colon cancer surgery.

Research frontiers

There is little information regarding the effect of hypoalbuminemia on the development of postoperative complications after rectal cancer surgery, and the results remain controversial.

Innovations and breakthroughs

The present study clearly demonstrates hypoalbuminemia is associated with an increased rate of complications, and has a negative impact on postoperative recovery following rectal cancer surgery.

Applications

Pre-operative assessment of patients with rectal cancer may routinely include serum albumin levels. Patients with pre-operative hypoalbuminemia should be informed about the higher rate of complications after rectal cancer surgery. Every effort to improve patients’ pre-operative malnourishment without delayed surgical treatment should be encouraged. Further research might focus on the effect of hypoalbuminemia on long-term surgical outcomes and cancer survival.

Terminology

Pre-operative hypoalbuminemia is an independent risk factor for postoperative complications following rectal cancer surgery.

Peer review

This is an interesting paper showing that hypoalbuminemia will have an impact on postoperative recovery and complication. It is well known that malnourished patients do worse than those with a good nutrition status in the postoperative course. It is well written, the data is excellent and references timely.

Acknowledgments

The authors are grateful to Mr. Suthipol Udompunturak (Clinical Epidemiology Unit, Office for Research and Development, Faculty of Medicine Siriraj Hospital, Mahidol University) for his excellent support in statistical analysis.

Peer reviewers: Lars A Pahlman, Professor, Department of Surgery, Colorectal Unit, University Hospital, SE 751 85, Uppsala, Sweden; Walter E Longo, Professor, Department of Surgery, Yale University School of Medicine, 205 Cedar Street, New Haven 06510, United States

S- Editor Zhu LH L- Editor Kerr C E- Editor Liu Y

References

1. Sungurtekin H, Sungurtekin U, Balci C, Zencir M, Erdem E. The influence of nutritional status on complications after major intraabdominal surgery. J Am Coll Nutr. 2004;23:227–232. [PubMed]
2. Miner TJ, Brennan MF, Jaques DP. A prospective, symptom related, outcomes analysis of 1022 palliative procedures for advanced cancer. Ann Surg. 2004;240:719–726; discussion 726-727. [PMC free article] [PubMed]
3. Inoue Y, Miki C, Kusunoki M. Nutritional status and cytokine-related protein breakdown in elderly patients with gastrointestinal malignancies. J Surg Oncol. 2004;86:91–98. [PubMed]
4. Fuhrman MP, Charney P, Mueller CM. Hepatic proteins and nutrition assessment. J Am Diet Assoc. 2004;104:1258–1264. [PubMed]
5. Lohsiriwat V, Chinswangwatanakul V, Lohsiriwat S, Akaraviputh T, Boonnuch W, Methasade A, Lohsiriwat D. Hypoalbuminemia is a predictor of delayed postoperative bowel function and poor surgical outcomes in right-sided colon cancer patients. Asia Pac J Clin Nutr. 2007;16:213–217. [PubMed]
6. Kudsk KA, Tolley EA, DeWitt RC, Janu PG, Blackwell AP, Yeary S, King BK. Preoperative albumin and surgical site identify surgical risk for major postoperative complications. JPEN J Parenter Enteral Nutr. 2003;27:1–9. [PubMed]
7. Kuzu MA, Terzioglu H, Genc V, Erkek AB, Ozban M, Sonyurek P, Elhan AH, Torun N. Preoperative nutritional risk assessment in predicting postoperative outcome in patients undergoing major surgery. World J Surg. 2006;30:378–390. [PubMed]
8. Shaw-Stiffel TA, Zarny LA, Pleban WE, Rosman DD, Rudolph RA, Bernstein LH. Effect of nutrition status and other factors on length of hospital stay after major gastrointestinal surgery. Nutrition. 1993;9:140–145. [PubMed]
9. Alves A, Panis Y, Mathieu P, Mantion G, Kwiatkowski F, Slim K. Postoperative mortality and morbidity in French patients undergoing colorectal surgery: results of a prospective multicenter study. Arch Surg. 2005;140:278–283, discussion 284. [PubMed]
10. Makela JT, Kiviniemi H, Laitinen S. Risk factors for anastomotic leakage after left-sided colorectal resection with rectal anastomosis. Dis Colon Rectum. 2003;46:653–660. [PubMed]
11. Gibbs J, Cull W, Henderson W, Daley J, Hur K, Khuri SF. Preoperative serum albumin level as a predictor of operative mortality and morbidity: results from the National VA Surgical Risk Study. Arch Surg. 1999;134:36–42. [PubMed]
12. Van Cutsem E, Arends J. The causes and consequences of cancer-associated malnutrition. Eur J Oncol Nurs. 2005;9 Suppl 2:S51–S63. [PubMed]
13. Gadducci A, Cosio S, Fanucchi A, Genazzani AR. Malnutrition and cachexia in ovarian cancer patients: pathophysiology and management. Anticancer Res. 2001;21:2941–2947. [PubMed]
14. Albrecht JT, Canada TW. Cachexia and anorexia in malignancy. Hematol Oncol Clin North Am. 1996;10:791–800. [PubMed]
15. Scarfone A, Capristo E, Valentini G, Addolorato G, Ghittoni G, Giancaterini A, Mingrone G, Greco AV, Gasbarrini G. Wasting in gastrointestinal tract cancers: clinical and etiologic aspects. Minerva Gastroenterol Dietol. 1999;45:261–270. [PubMed]
16. Rivadeneira DE, Evoy D, Fahey TJ 3rd, Lieberman MD, Daly JM. Nutritional support of the cancer patient. CA Cancer J Clin. 1998;48:69–80. [PubMed]
17. Longo WE, Virgo KS, Johnson FE, Oprian CA, Vernava AM, Wade TP, Phelan MA, Henderson WG, Daley J, Khuri SF. Risk factors for morbidity and mortality after colectomy for colon cancer. Dis Colon Rectum. 2000;43:83–91. [PubMed]
18. Ryan AM, Hearty A, Prichard RS, Cunningham A, Rowley SP, Reynolds JV. Association of hypoalbuminemia on the first postoperative day and complications following esophagectomy. J Gastrointest Surg. 2007;11:1355–1360. [PubMed]
19. Irvin TT, Hunt TK. Effect of malnutrition on colonic healing. Ann Surg. 1974;180:765–772. [PMC free article] [PubMed]
20. Ward MW, Danzi M, Lewin MR, Rennie MJ, Clark CG. The effects of subclinical malnutrition and refeeding on the healing of experimental colonic anastomoses. Br J Surg. 1982;69:308–310. [PubMed]
21. Testini M, Margari A, Amoruso M, Lissidini G, Bonomo GM. The dehiscence of colorectal anastomoses: the risk factors. Ann Ital Chir. 2000;71:433–440. [PubMed]
22. Reynolds JV, Redmond HP, Ueno N, Steigman C, Ziegler MM, Daly JM, Johnston RB Jr. Impairment of macrophage activation and granuloma formation by protein deprivation in mice. Cell Immunol. 1992;139:493–504. [PubMed]
23. Rivadeneira DE, Grobmyer SR, Naama HA, Mackrell PJ, Mestre JR, Stapleton PP, Daly JM. Malnutrition-induced macrophage apoptosis. Surgery. 2001;129:617–625. [PubMed]
24. Margarson MP, Soni N. Serum albumin: touchstone or totem? Anaesthesia. 1998;53:789–803. [PubMed]
25. Bromenshenkel J, Newcomb M, Thompson J. Continuous quality improvement efforts decrease postoperative ileus rates. J Healthc Qual. 2000;22:4–7; quiz 7, 15. [PubMed]
26. Mattei P, Rombeau JL. Review of the pathophysiology and management of postoperative ileus. World J Surg. 2006;30:1382–1391. [PubMed]
27. Delaney CP. Clinical perspective on postoperative ileus and the effect of opiates. Neurogastroenterol Motil. 2004;16 Suppl 2:61–66. [PubMed]
28. Rubin H, Carlson S, DeMeo M, Ganger D, Craig RM. Randomized, double-blind study of intravenous human albumin in hypoalbuminemic patients receiving total parenteral nutrition. Crit Care Med. 1997;25:249–252. [PubMed]
29. Woods MS, Kelley H. Oncotic pressure, albumin and ileus: the effect of albumin replacement on postoperative ileus. Am Surg. 1993;59:758–763. [PubMed]
30. Moskovitz DN, Kim YI. Does perioperative immunonutrition reduce postoperative complications in patients with gastrointestinal cancer undergoing operations? Nutr Rev. 2004;62:443–447. [PubMed]

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