Abstract
Background: Colorectal cancer is predominantly a disease of the elderly in whom the incidence of malnutrition has been estimated at about 5-6% between the ages of 70 and 80 and 8-12% over the age of 80. Most patients with colorectal cancer admitted for elective surgery appear well nourished on admission but leave hospital looking under-nourished. We attempt to quantify this in an effort to understand which direction further studies and even clinical intervention might take.
Study design: Case notes of fifty patients who have undergone resection surgery for colorectal cancer at The James Cook University Hospital over a five year period were reviewed and data extracted. The prevalence of malnutrition and the effects of preoperative BMI and serum albumin on length of hospital stay, days off food and complications were studied.
Results: The prevalence of malnutrition (BMI < 20kg/m2) was 6.0%. More patients were obese/overweight (48%) than were malnourished. There was no correlation between BMI on admission and length of hospital stay (P = 0.88).
Conclusion: There were more overweight/obese than undernourished patients on admission. The BMI on admission did not affect the length of hospital stay. The drop in albumin concentration had a negative correlation with the number days off food. Hypoalbuminaemia did not increase the rate of wound infection.
Introduction
A 40% prevalence of malnutrition (body mass index (BMI) < 20 kg/m2) has been reported amongst hospitalised patients on admission1. About two-thirds of these patients lose weight whilst in hospital, protein calorie malnutrition (PCM) being the most prevalent amongst surgical patients2. Colorectal cancer patients are susceptible to protein calorie malnutrition and may be malnourished at the time of presentation as a result of poor nutrient intake and increased nutrient requirement as part of the cancer cachexia syndrome or develop malnutrition in course of treatment although some may even paradoxically appear overweight.3, 4. Serum albumin and body weight are the most commonly measured indices of nutritional assessment. The body mass index [BMI = Weight (kg)/height (m2)] or percentage weight loss are simple and sensitive clinical measures of gross nutritional status5. The ideal BMI is 20-25 kg/m2. A BMI of less than 20 kg/m2 indicates the possibility of undernutrition while a BMI of less than 18 kg/m2 is suggestive of undernutrition.5 Pre-treatment serum albumin level has been shown to be an independent prognostic factor in a number of malignant diseases6, 7. Reinhardt et al demonstrated a linear correlation between the degree of hypoalbuminaemia and the thirty-day mortality in hospitalised patients. They found a thirty day mortality rate of 24.6% in hypoalbuminaemic (albumin < 3.4gm/dl) patients compared with 1.7% in patients with normal albumin. They showed that a one gram drop in serum albumin level (3.5 to 2.5 gm/dl) translated into a 35% increase in mortality8. Serum albumin level is said to probably be the best indicator of survival in cancer patients9. Traditionally, serum albumin has been used as an index of nutritional assessment10, 11, 12, 13. and is useful if estimated serially14. Serum albumin concentrations are influenced by numerous factors including the state of hydration of the patients, its distribution between extra-cellular and intra-cellular fluid compartments, rate of synthesis and breakdown. Nutrient intake (total calories and specific amino acids) is the primary determinant of the rate of synthesis. The oncotic pressure of the hepatocytes also influence albumin synthesis – a decrease in pressure increasing rate of albumin synthesis. Synthesis is decreased during periods of decreased food intake15. Thirty gram per litre (30gm/litre) is the level below which it is said to indicate nutritional deficiency. However its rate of fall is said to be a determinant of the nature the nature of the illness and its outcome16. The main criticism of albumin as a nutritional marker is its long life of twenty one days. This makes it not a very sensitive indicator of early protein deficiency and therefore said to be inappropriate as a marker of nutritional status in short-term starvation. Nevertheless, it still remains a reliable common biochemical parameter in nutritional assessment11. Hypoalbuminaemia is a poor prognostic sign in cancer patients17. Hermann et al studied serum albumin levels within 48 hours of hospitalisation for acute illness to predict in hospital death, length of hospitalisation and re-admission rate in 15,511 patients older than forty years. Patients with serum albumin less than 34g/l (21% of the study population), were more likely to die (in hospital mortality of 14%), stayed longer in hospital when compared with those with normal serum albumin (in hospital mortality of 4%). They concluded that serum albumin level was independent for age and was a stronger predictor of outcome than age or other laboratory indices18. Surgery in the undernourished results in impairment of wound healing19, 20 increases wound infection rate21, 22, increased incidence of anastomotic dehiscence23 and delays recovery.
Patients and Methods
The aim of this retrospective study was to establish the effect of pre-operative serum albumin and body mass index on post-operative outcome, including morbidity, mortality and hospital stay in colorectal cancer patients who have undergone resection surgery.
Medical notes of fifty patients who had undergone resection colorectal surgery for a five year period from 1994 to 1999 for colorectal cancer with histological confirmation, grading and staging were studied and the data in table 1 were extracted.
Patients operated upon for benign colorectal conditions such as polyps with severe dysplasia, diverticular disease, Crohn’s, ulcerative colitis and patients with intercurrent medical conditions - diabetes mellitus and pre-existing chronic renal failure were excluded from the study as these patients already had impaired metabolism and patients who had emergency operations were excluded from the study .
Astler and Coller’s modification24 of Dukes’ classification was routinely used by the pathology department for staging and tumours were graded as well, moderately or poorly differentiated. Patients were grouped into four groups based on their BMI on admission (Table 2).
Definition Of Malnutrition: For the purpose of this study, malnutrition was defined as BMI < 20kg/m2, (1.,5) or serum albumin concentration < 35gm/l25. BMI >25kg/m2 was defined as overweight/obese.
Major complications were defined as untoward events that threatened life or prolonged hospital stay3.
1. Postoperative septicaemia was defined as body temperature > 37.5°C with a positive blood culture, leucocytosis or leucopenia,
2. Intra-abdominal sepsis as intra-abdominal purulent collection requiring ultrasound or CT guided or open drainage.
3. A fistula was defined as an enterocutaneous or colocutaneous connection confirmed radiologically,
4. pneumonia as chest infection with positive sputum culture with an abnormal chest X-ray requiring antibiotic treatment.
5. Wound infection was defined as purulent wound discharge with positive swab culture and was scored using the ASEPSIS scoring system26
6. Post operative ileus as abnormal bowel function with or without vomiting requiring nasogastric intubation and cessation of oral fluids,
7. Urinary tract infection (UTI) as significant bacteriuria (105),
8. Pseudomembranous colitis as post-operative diarrhoea with isolation of Clostridium diffcille with or without endoscopic confirmation,
9. Sinus as a connection of skin or any epithelial surface to a deep seated abscess and
10. Post operative mortality as death that occurs following operation in patients who have been hospitalised continually or discharged home since operation until thirty days.
Statistical analysis: The Statistical Package for Social Science (SPSS,Chicago,Illinois,USA) software was used for data analysis. Normally distributed (parametric) data such as albumin concentration were calculated as mean (SD, standard deviation) and 95% confidence interval of the mean (CI) and analysed using variance (ANOVA). Continuous non-parametric data such as days in hospital were calculated as medians and analysed with Kruskal Wallis test. T-test and Paired T-test were used to test difference in means were appropriate. The effects of hypoalbuminaemia on length of hospital stay were analysed with Mann-Whitney test and Fisher’s test was used to test effects of hypoalbuminaemia on wound infection. Wound infection scores were analysed with Chi square test. T – test and paired T- tests were used to test differences in mean were appropriate. Statistical difference was set at P < 0.05.
Results
There were 33 males and 17 females (male: female ratio of 1.9: 1) with a mean age of 68.4±9.8 years (range 40-88 years).
BMI At Presentation: The mean BMI at presentation was 25.5(± 4.1, range 17.3-35.4)kg/m2. (Table 2) See Illustration 2
Albumin On Admission: The mean albumin on admission and discharge were 42.8gm/l (SD 4.9, range 30-52gm/dl) and 35.1(SD5.3, range 21-44) gm/l respectively. Four patients (8%) presented with albumin of <35gm/l) (Two with 33 and one each with 30 and 32gm/l). All four patients had normal body mass index at presentation. Twenty four (48%) patients were discharged with serum albumin concentration of < 35g/l. The mean drop in albumin concentration between admission and discharge was 7.7 (± 4.2, range 0.0 to 17.0) gm/l. The drop had a significant negative correlation with the number of days off food after surgery (P = 0.04). The longer the length of hospital stay and length of postoperative starvation, the larger the drop in albumin concentration.
Days In Hospital and Days Off Food:
See Illustration 3
The BMI on admission did not affect the length of hospital stay (P=0.88) or the median days off food after surgery (P=0.69)
Complications: 11 of 24 patients (45.8%) with BMI of 20-25 kg/m2 developed a total of 27 complications, 6 of 17 patients (35%) of those with BMI of 25-30kg/m2 developed a total of 10 complications while 4 of 6 patients (66.7%) of patients with BMI > 30 developed 7 complications. 1 of 3 patients with BMI < 20kg/m2 developed a total of 2 complications. Two patients presented with normal serum albumin and BMI < 20kg/m2. One patient developed pseudomembranous colitis (antibiotic associated colitis) while the second patient developed no complications. Two other patients presented who with low serum albumin but BMI > 30kg/m2. Both developed wound infection, wound dehiscence and oedema post-operatively (Table 4).
Deaths: There were two deaths (4%) one in the nourished group (BMI 20-25kg/m2) and the other in obese group (BMI > 30kg/m2). One of the deaths was an 82 year old male with a BMI of 23.1 kg/m2 with a pre-admission albumin of 44gm/dl who developed faecal peritonitis from anastomotic leak and pneumonia. Re-laparatomy showed ischaemic segment of bowel at the anastomotic site. He was fed parenterally on the 13th post-operative day and died four days later in the Intensive Care Unit. The second death was a 72-year- old female who presented with a BMI of 33.5kg/m2 and a serum albumin of 30gm/dl. She developed wound dehiscence, vomiting, sepsis, wound infection, hypoproteinaemia, hypoalbuminaemia and oedema and died ten days post surgery.
Discussion
Forty six percent (46%) of patients in this study presented with BMI of >25+ kg/m2 (either over weight or obese) and 6 % were under-nourished with BMI < 20kg/m2. There were more overweight/obese patients than malnourished patients.
Hickman et al3 in their series from 1958 to 1978 also found more obese/overweight patients with colorectal cancer (34%) than patients with low weight (22%) at the time of admission. Malnutrition and obesity pose problem in the post-operative period. The over weight and obese are particularly at risk if oral intake is delayed as their nutritional requirements tend to be overlooked because of their weight. They tend to burn off their muscle bulk but still appear fat and overweight27. In this study, 33.3% of patients with BMI < 20kg/m and 66.7% of patients with BMI >30kg/m developed postoperative complications. At the time of this study, patients were not routinely weighed on admission and whilst in hospital and as such inferences could not be made on weight changes or BMI changes between admission and discharge.
The prevalence of malnutrition by albumin concentration of < 35g/l was 8% on admission and 48% on discharge. Bistrian et al28 found a 44% incidence of malnutrition based on serum albumin of < 35g/l amongst 251 medical patients with varying diagnosis which included alcoholism, gastrointestinal, liver, metabolic and infectious diseases. A Scandinavian study found a 5% prevalence of protein energy malnutrition using parameters including BMI, hypoalbuminaemia in 1206 randomly selected adults29. Mullen et al30 however found 16% prevalence of malnutrition based on hypoalbuminaemia. Patients in all these studies had various diagnosis which included oesophageal and gastric cancers and had varying degrees of eating problems unlike the patients in this study none of whom had any eating problems and all had the same diagnosis.
The drop in serum albumin concentration was 7.4 ± 4.2gm/l and had a significant negative correlation with the number of days off food after surgery (P=0.04). Silkman et al31 in a randomised study of patients, who had had colonic surgery, showed that infusion of nutrient containing supplementary glucose resulted in an impressive and statistically significant increase in the rate of albumin synthesis. It has been shown that during starvation muscle proteins are broken down for gluconeogenesis and for the albumin synthesis. Albumin is normally manufactured in the liver mainly from exogenous precursors and the rate of synthesis is dependent on nutrient intake. Fasting, specifically omitting protein from the diet has also been shown to reduce albumin synthesis32. Prolonged post-operative starvation decreases albumin synthesis and nutritional supplementation in the peri-operative period is therefore crucial. Albumin concentration is however also affected by its redistribution in the body’s compartments.
One patient in each study had generalised oedema due to severe hypoalbuminaemia. Muscle protein breakdown for gluconeogenesis and reduced food intake are the main causes of hypoalbuminaemia in the cancer patient. Hypoalbuminaemia also did not influence the incidence of wound infection. Kudsk K A et al33 found a low incidence of complications for patients with colorectal cancer with the same level of albumin when compared with oesophageal or pancreatic cancer (29% versus 100%). They also found that there was a low incidence of mortality if the serum albumin levels were above 32gm/l but as the serum albumin fell below 32gm/l, the incidence of mortality progressively increased regardless of the site of the surgery.
Serum albumin levels correlate well with dietary protein intake30, therefore, delayed exogenous protein intake could explain the fall in albumin levels although it could be argued that the levels could have been affected by the state of hydration of these patients. However, all fifty patients in this study were well hydrated and had normal renal and liver functions. The change in albumin in this study correlated with the level of albumin on admission-the higher the level on admission the larger the difference on discharge. The patients with lower serum albumin on admission conserving enough serum albumin required to maintain plasma oncotic pressure necessary to sustain life
There were no significant differences in the complications in the nourished and malnourished groups. This could be explained by the small sample size. It has recently been shown that weight loss is a basic indicator of surgical risk in modern surgical patients only when it is associated with clinically obvious impairment of organ function34. None of the patients in this study showed any impairment of organ function on admission.
The change in albumin concentration could have been reduced by providing patients very early in the post-operative period with exogenous protein enterally as this reduces the period of starvation and may reduce hospital stay.
Conclusion
The prevalence of malnutrition (BMI < 20kg/m2) was 6.0%. More patients (48%) were obese/overweight (BMI >25kg/m2) than were malnourished. There was no correlation between BMI on admission and length of hospital stay (P = 0.88). The BMI on admission did not affect the length of hospital stay. The drop in albumin concentration had a negative correlation with the number days off food. Hypoalbuminaemia did not increase the rate of wound infection.
In the treatment of colorectal cancer patients, nutritional assessment should form part of the pre-assessment process. This will identify those at risk of post-operative complication even if they look physically fit or overweight. Serious thought should be given to nutritional support in the elderly and if the period of starvation exceeds five days especially in institutions where fast-track recovery is not practised after colorectal resection, as this will minimise serious complications and reduce hospital stay.
Acknowledgements
I wish to thank Mrs Vicky Whittaker of Teesside University for statistical advice and Prof R.G. Wilson MD, FRCS for giving me the opportunity to perform this study.
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