Anorexia and malnutrition in patients with obstructive jaundice

Anorexia and malnutrition in patients with obstructive jaundice

NUTRITION SUPPORT IN SPECIFIC SURGICAL CONDITIONS Anorexia and Malnutrition in Patients With Obstructive Jaundice F. J. Padillo, B. Andicoberry, C. P...

65KB Sizes 0 Downloads 66 Views

NUTRITION SUPPORT IN SPECIFIC SURGICAL CONDITIONS

Anorexia and Malnutrition in Patients With Obstructive Jaundice F. J. Padillo, B. Andicoberry, C. Pera-Madrazo, and A. Sitges-Serra From the Department of Surgery and the Department of Nutrition, Hospital Universitario Reina Sofı´a, Co´rdoba, Spain; and the Department of Surgery, Hospital Universitari del Mar, Barcelona, Spain INTRODUCTION Obstructive jaundice may be due to benign conditions (most often, common bile duct stones, Mirizzi’s syndrome, or chronic pancreatitis) or malignant tumors. Patients with malignant obstructive jaundice may have severe weight loss and malnutrition, but the role of the tumor per se in the pathophysiology of nutrition derangements associated with biliary obstruction may be difficult to differentiate from that of jaundice alone.1–3 In patients with biliary tract obstruction, surgery is often indicated. Controlled observational studies have suggested that preoperative identification and treatment of nutritional deficiencies may improve the outcome of surgery.4 – 6 Therefore, it seems important to analyze the severity and type of malnutrition in benign and malignant biliary obstructions and to identify the factors associated with nutrition derangements in these conditions.

NUTRITION STATUS AND FOOD INTAKE ALTERATIONS IN OBSTRUCTIVE JAUNDICE More than 50% of patients with biliary obstruction may present nutrition disorders. The majority of patients suffer from mild to moderate protein-calorie malnutrition, with fewer than 10% presenting with severe undernutrition. Severe undernutrition is seen mostly in patients with malignant obstruction in whom nutrition risk scores are greater than in patients with benign conditions. The severity of malnutrition also seems to be associated with the intensity and the duration of jaundice.7,8 According to Chang’s criteria,9 malnutrition is predominantly of the kwashiorkor type in benign biliary obstruction, whereas more than 30% of patients with obstructive jaundice secondary to malignant disease present a mixed type of malnutrition.7 Thus it may be hypothesized that, in addition to the nutrition deficiencies associated with malignant neoplasms, patients with obstruction of the biliary tract might suffer from poor nutrient intake related to the exclusion of bile from intestine. Further, an inflammatory response to low grade infection may be present and lead to visceral protein depletion. Clinical10 –12 and experimental13 studies have shown that bile duct obstruction leads to hypodipsia and hypophagia. When the prevalence of anorexia was investigated at admission in patients with biliary obstruction, over two-thirds had a spontaneous food intake below their calorie requirements.12 There were no significant differences between patients with benign or malignant conditions.

Correspondence to: F. J. Padillo, Departamento de Cirugı´a, Hospital Universitario Reina Sofı´a, Menendez Pidal s/n, 14004 Co´rdoba, Spain. E-mail: [email protected] Nutrition 18:987–990, 2002 ©Elsevier Science Inc., 2002. Printed in the United States. All rights reserved.

Thus, a proper nutrition assessment is justified in patients with obstructive jaundice to detect those at high nutritional risk in whom an intensive nutrition support or early biliary drainage might be necessary, especially if surgery is indicated.

SPECIFIC CONSIDERATIONS OF NUTRITION ASSESSMENT IN PATIENTS WITH BILIARY OBSTRUCTION There is no general agreement on the best approach for the nutrition assessment of individual patients.14 –20 Parameters used for the evaluation of nutrition status of hospitalized patients may be altered by disease and are not specific markers of malnutrition. Serum albumin concentrations, the only biochemical “nutrition index” routinely available for many clinicians, are often in the lower limit of normal in patients with benign obstruction, whereas they are often severely depleted in patients with malignant tumors. The low frequency of severe hypoalbuminemia in benign obstructive jaundice may contribute to the underestimation of the nutritional problems of such patients. It should be emphasized that close to 50% of patients with normal values of serum albumin may have malnutrition as defined by other criteria.7 This can be explained by a reduced extracellular water and plasma volume present in these patients,21–23 which may, at least in part, be responsible for the loss of weight and the spuriously normal albumin concentrations. As suggested by others17,24 in different clinical settings, the concentration of plasma proteins with short half-lives, such as transferrin or prealbumin, may be helpful to properly assess the nutrition status in patients with obstructive jaundice. Retinolbinding protein, however, offers no clear indication on the nutrition status in these patients because it is highly sensitive to the slightest stress25 and its clearance is impaired by renal dysfunction, which is found so often in patients with obstructive jaundice.26 According to these observations, a combined nutrition assessment, including biochemical, anthropometric, and functional evaluations, should be done for a proper evaluation of nutrition derangements in patients with biliary tract obstruction.

FACTORS ASSOCIATED WITH ANOREXIA AND MALNUTRITION Etiology of Obstruction Although malnutrition is common with benign or malignant obstruction, weight loss and hypoalbuminemia are more common and severe in patients with malignant obstructions. This may be de to a chronic reduction of food intake and an acute-phase response secondary to the activity of tumor necrosis factor-␣ and other proinflammatory cytokines that may downregulate albumin syn0899-9007/02/$22.00 PII S0899-9007(02)00982-6

988

Padillo et al.

FIG. 1. Correlation between plasma concentration of CCK (pM/L) and caloric intake (%; r ⫽ ⫺0.7, P ⬍ 0.001) in 62 patients with obstructive jaundice. From Padillo et al.12 CCK, cholecystokinin.

thesis and induce an increase of the energy expenditure.27–29 Tumor necrosis factor-␣ is a cytokine that acts as a cachectin associated with cancer and endotoxemic status.30 –32 Several studies have shown that levels of tumor necrosis factor-␣ are increased in patients with prolonged malignant biliary obstruction with severe malnutrition in whom a positive acute-phase response is present.33,34 The acute-phase response in patients with cancer or biliary infections may result from a defensive immune response of the host or from the production of cytokines by the tumor itself or macrophages. This has been associated with increased mortality.28,35 In a sustained scenario of increased endotoxin and acutephase response, protein-calorie depletion is enhanced, thus contributing to the worsening of the patient’s condition; this could be crucial in patients with biliary tract obstruction when surgery is required.30,32,36,37 Mediators of Anorexia The prevalence of malnutrition is associated with the intensity of biliary obstruction. This finding suggested that absence of bile into the duodenum may induce stimulation of anorexia mediators. Clinical38 – 40 and experimental41,42 studies have linked regulation of plasma cholecystokinin (CCK) levels closely to the presence of bile acids (in particular chenodeoxycholic acid) in the duodenal lumen, to the proper digestion of dietary fats,43 and to the presence of protease within the duodenum.44 The presence of bile in the gut exerts a negative feedback on CCK secretion. In contrast, in patients with biliary tract obstruction, the absence of bile within the duodenum and the consequent accumulation of bile components in the blood is accompanied by increased plasma CCK levels. CCK is involved in biliopancreatic physiology by stimulating the secretion of bile and pancreatic enzymes. Several studies have shown that CCK has considerable anorectic properties.45,46 CCK acts as a neuropeptide, in the central nucleus of satiety through the “brain– gut axis,” and in the digestive tract by decreasing gastric contractions, thus slowing down the rate of gastric emptying.47,48 Experimental studies49 have shown that the use of a specific CCK receptor antagonist (L-364, 718) in rats with bile duct ligation caused an increase in food intake when compared with controls. In addition, CCK plasma levels closely correlates with food intake alterations12 (Fig. 1) and with the nutrition status of jaundiced patients.8 Although CCK seems to be an excellent candidate molecule for mediating anorexia, the final proof of its role should come from studies in which its effects could be blocked by a specific CCK receptor antagonist administered to patients with obstructive jaundice.

Nutrition Volume 18, Number 11/12, 2002 Secretin, a hormone related to the biliopancreatic physiology, which also might be involved in inducing satiety by slowing down the rate of gastric emptying, also has been evaluated as an anorectic factor in patients with biliary obstruction.12 However, we found no association between secretin levels and anorexia in that study. Moreover, no changes in plasma secretin concentrations were found in jaundiced patients when compared with healthy subjects.12 Leptin, a protein released from adipocytes, has been identified recently as a potent circulating satiety factor. Proopiomelanocortin and neuropeptide Y types of neurons in the arcuate nucleus of the hypothalamus are principal sites of leptin receptor expression and the source of potent neuropeptide modulators, melanocortins, and neuropeptide Y, which exert opposing effects on feeding and metabolism.50 In an experimental study, leptin production was significantly increased early after biliary obstruction but reduced after prolonged biliary obstruction.51 As suggested by the investigators, the increased circulating leptin levels may contribute to the profound anorexia observed early after biliary obstruction in rats but appears not to mediate the anorexia observed during more chronic experimental biliary obstruction. There are no data, however, concerning the potential role of leptin in food intake alterations in patients with biliary obstruction. Liver Dysfunction Obstruction of the biliary tract usually leads to a moderate impairment of liver function. Prolonged increased in cytokines levels also may alter liver metabolism by blocking the synthesis and expression of the cytochrome P450s in human hepatocytes and the transcription of negative acute-phase proteins (such as albumin) in these cells.52 Malnutrition is more frequent in patients with marked liver dysfunction and low anabolic capacity.53 Jaundiced patients with malnutrition criteria show higher levels of alanine aminotransferase than do those without malnutrition. Moreover, as observed by the investigators, alanine aminotransferase plasma determination might be used as prognostic factor for malnutrition in patients with biliary tract obstruction.8

EFFECT OF BILIARY DRAINAGE ON ANOREXIA AND NUTRITION MARKERS Prospective54 –56 and retrospective10,57,58 studies have examined the impact of biliary drainage on various pathogenic aspects of obstructive jaundice. Most of these, however, used external drainage, which has yielded poorer results than internal drainage because it involves partial or total diversion of bile away from the duodenum. Studies of percutaneous biliary drainage, apart from requiring external or mixed drainage for 24 to 48 h, may yield worse nutrition results because of the pain caused by the continued presence of percutaneous catheters that may interfere with return to normal eating. Studies performed using internal biliary drainage found that, 10 d after successful drainage, nutrition markers improved significantly, mainly associated with an improvement in short half-life protein concentration.56 The prognostic nutrition index, which also included visceral proteins with short half-lives, proved to be extremely sensitive in detecting changes in nutrition status during the first 10 d after biliary drainage. There was an overall increase in the prognostic nutrition index, although only patients with benign obstruction had values close to normal, whereas those with malignant obstruction continued to be at high nutrition risk 10 d after bile flow restoration. The improvement of oral intake and nutrition state of patients with obstructive jaundice after biliary drainage may be linked to increased appetite.10,12 Spontaneous food intake improves signif-

Nutrition Volume 18, Number 11/12, 2002

FIG. 2. Improvement of food intake (kcal/d) after internal biliary drainage in benign obstruction (squares; P ⬍ 0.01) and malignant (circles; P ⬍ 0.05) tumors. From Padillo et al.12

icantly after biliary drainage in patients with benign or malignant obstruction (Fig. 2). However, more than 50% of patients with cancer maintained food intakes below the estimated calorie requirements 1 wk after internal biliary drainage.12 These findings suggested that, regardless of the degree of anorexia associated with malignancy, obstruction of the bile duct per se causes significant changes in food intake that revert after biliary decompression. Moreover, once bile flow to the duodenum is re-established after endoscopic internal drainage, plasma CCK levels decrease dramatically and promptly.12 This agrees with clinical and experimental studies closely linking regulation of plasma CCK levels to the presence of bile acids in the duodenum.38 – 42 Conversely, cytokines and liver function markers that are related to food intake also decrease after biliary drainage, thus contributing to nutritional recovery.

CONCLUSION In summary, protein-calorie malnutrition is often observed in patients with obstructive jaundice. Despite the potential metabolic interference of the tumor in patients with malignant disease, bile duct obstruction per se is associated with significant changes in food intake. Anorexia and malnutrition seem to be related to the intensity of biliary obstruction, liver injury, and anorectic endocrine mediators such as CCK and leptin. The restoration of bile flow into the duodenum after internal drainage determines early improvement in food intake alterations that is accompanied by a slow improvement in nutrition markers.

REFERENCES 1. Ishida Y, Nagao T, Uchida H. Nutritional and immunological assessment in patients with malignant obstructive jaundice—the influence of preoperative biliary decompression and abdominal surgery. Nippon Geka Gakkai Zasshi 1994; 95:71 2. Sherlock S. Diseases of the liver and biliary system. Boston: Blackwell Scientific Publications, 1989:248 3. Rege RV. Adverse effects of biliary obstruction: implications for treatment of patients with obstructive jaundice. AJR 1995;164:287 4. Padillo FJ, Canis M, Rufia´ n S, et al. The palliative treatment of pancreatic cancer: percutaneous drainage versus surgical diversion. Rev Esp Enf Digest 1992;81: 337 5. Mullen JL, Buzby GP, Mattews DC. Reduction of operative morbidity and mortality by combined preoperative and postoperative nutritional support. Ann Surg 1981;192:604

Anorexia, Malnutrition, and Jaundice

989

6. Buzby GP, Williford WO, Peterson O. A randomized clinical trial of TPN in malnourished surgical patients: the rationale and impact of previous clinical trials and pilot study on the protocol design. Am J Clin Nutr 1988;47:357 7. Padillo FJ, Rodriguez M, Hervas A, et al. Nutritional assessment of patients with benign and malignant obstructions of the biliary tract. Rev Esp Enferm Dig 1999;91:622 8. Padillo FJ, Andicoberry B, Muntane´ J, et al. Factors predicting nutritional derangements in patients with obstructive jaundice: a multivariate analysis. World J Surg 2001;25:67 9. Chang RWS. Nutritional assessment using a microcomputer. 1. Programme design. Clin Nutr 1984;3:67 10. Ballinger AB, McHugh M, Catnach SM, Alstead EM, Clark ML. Symptom relief and quality of life after stenting for malignant bile duct obstruction. Gut 1994; 35:467 11. Andicoberry B, Padillo FJ, Go´ mez-Alvarez M, et al. Evaluation of anorexia in patients with bile duct obstruction. Nutr Hosp 1999;14:38 12. Padillo FJ, Andicoberry B, Naranjo A, et al. Anorexia and the effect of internal biliary drainage on food intake in patients with obstructive jaundice. J Am Coll Surg 2001;192:584 13. Valverde J, Martı´nez-Ro´ denas F, Pereira JA, et al. Rapid increase in plasma levels of atrial natriuretic peptide after common bile duct ligation in the rabbit. Ann Surg 1992;216:554 14. Sitges-Serra A, Franch G. Nutrition assessment. In: Payne-James J, Grimble G, Silk D, eds. Artificial nutritional support in clinical practice. Sevenoaks, UK: Edward Arnold, 1995 15. Frisancho AR. Triceps skinfold and upper arm size norms for assessment of nutritional status. Am J Clin Nutr 1974;27:1052 16. Durning JVGA, Rahaman MM. The assessment of the amount of fat in the human body measurements of skinfold thickness. Br J Nutr 1967;21:681 17. Young GA, Hill GL. Assessment of protein calorie malnutrition in surgical patients from plasma proteins and anthropometric measurements. Am J Clin Nutr 1972;31:429 18. Jensen TG, Englert DM, Dudrick SJ. Nutritional assessment: a manual for practitioners. Norwalk, CT: Appleton-Century-Crofts, 1983 19. Tuten MB, Wogt S, Dasse F, Leider Z. Utilization of prealbumin as a nutritional parameter. JPEN 1983;9:709 20. Dempsey DT, Mullen JL, Buzby GP. The link between nutritional status and clinical outcome: can nutritional intervention modify it? Am J Clin Nutr 1988; 47:352 21. Sitges-Serra A, Carulla X, Piera C, et al. Body water compartments in patients with obstructive jaundice. Br J Surg 1992;79:553 22. Gallardo JM, Padillo FJ, Martı´n-Malo A, et al. Increased plasma levels of atrial natriuretic peptide and endocrine markers of volume depletion in patients with obstructive jaundice. Br J Surg 1998;85:28 23. Padillo FJ, Rodrı´guez M, Gallardo JM, et al. Preoperative assessment of body fluid disturbances in patients with obstructive jaundice. World J Surg 1999;23: 681 24. Mullen JL, Gertner MH, Buzby GP, Goodhart SL, Rosato EF. Implications of malnutrition in the surgical patients. Arch Surg 1979;114:121 25. Inoue Y, Okada A, Nezu R. Rapid turnover protein as index of nutritional status in benign diseases. Nutrition 1990;7:45 26. Grant JP, Custer PB, Thurloiw J. Current techniques of nutritional assessment. Surg Clin North Am 1981;61:437 27. Kowalski-Saunders PWJ, Winwood PJ, Arthur MJP, Wright R. Reversible inhibition of albumin production by rat hepatocytes maintained in a laminin-rich gel (Engdbroh-Holm-Susarm) in response to secretory products of Kupffer cells and cytokines. Hepatology 1992;16:733 28. Falconer JS, Fearon KCH, Plester CE, Ross JA, Carter DC. Cytokines, the acute-phase response and resting energy expenditure in cachectic patients with pancreatic cancer. Ann Surg 1994;219:325 29. Fearon KCH, Falconer JS, Slater C, et al. Albumin synthesis rates are not decreased in hypoalbuminemic cachectic cancer patients with an ongoing acutephase protein response. Ann Surg 1998;227:249 30. Santi G, Ilyin SE, Plata-Salaman CR. Anorexia induced by cytokine interaction at pathophysiological concentrations. Am J Physiol 1996;270:1394 31. Plata-Salaman CR. Anorexia induced by activators of the signal transducer gp130. Neuroreport 1996;7:841 32. Sanaf P, Frederich RC, Turner EM, et al. Multiple cytokines and acute inflammation raise mouse leptin levels: potential role in inflammatory anorexia. J Exp Med 1997;185:171 33. Puntis MC, Jiang WG. Plasma cytokine levels and monocyte activation in patients with obstructive jaundice. J Gastroenterol Hepatol 1996;11:7 34. Padillo FJ, Andicoberry B, Muntane´ J, et al. Cytokines and acute-phase response markers derangements in patients with obstructive jaundice. Hepatogastroenterology 2001;48:378

990

Padillo et al.

35. DeWys WD, Eastern Co-operative Oncology Group. Prognostic effect of weight loss prior to chemotherapy in cancer patients. Am J Med 1980;69:491 36. Espat NJ, Lopeland EM, Moldawer LL. Tumor necrosis factor and cachexia: a current perspective. Surg Oncol 1994;3:255 37. Tompkins RG. The role of proinflammatory cytokines in inflammatory metabolic responses. Ann Surg 1997;225:243 38. Koop J, Koop H, Gerhardt C, Schafmayer A, Arnold R. Do bile acids exert a negative feedback control of cholecystokinin release? Scand J Gastroenterol 1989;24:315 39. Koop I. Role of bile acids in the control of pancreatic secretion and CCK release. Eur J Clin Invest 1990;20:51 40. Schmidt WE, Creutzfeldt W, Hocker M, et al. Cholecystokinin receptor antagonist loxiglumide modulates plasma levels of gastro-entero-pancreatic hormones in man. Feedback control of cholecystokinin and gastrin secretion. Eur J Clin Invest 1991;21:501 41. Nakamura R, Miyasaka K, Kuyama Y, Kitami K. Luminal bile regulates cholecystokinin release in conscious rats. Dig Dis Sci 1990;35:55 42. Izukura M, Hashimoto T, Gomez G, et al. Intracolonic infusion of bile salt stimulates release of peptide YY and inhibits cholecystokinin-stimulated pancreatic exocrine secretion in conscious dogs. Pancreas 1991;6:427 43. Hildebrand P, Petrig C, Burckhardt B, et al. Hydrolysis of dietary fat by pancreatic lipase stimulates cholecystokinin release. Gastroenterology 1998;114: 123 44. Thimister PWL, Hopman WPM, Sloots CEJ, et al. Role of intraduodenal proteases in plasma cholecystokinin and pancreaticobiliary responses to protein and amino acids. Gastroenterology 1996;110:567 45. Reidelberger RD, Varga G, Liehr RM, et al. Cholecystokinin suppresses food intake by a nonendocrine mechanism in rats. Am J Physiol 1994;267:901 46. Zittel TT, von Elm B, Teichmann RK, Rabould HE, Becker HD. Cholecystokinin is partly responsible for reduced food intake and body weight loss after total gastrectomy in rats. Am J Surg 1995;169:265

Nutrition Volume 18, Number 11/12, 2002 47. Crawley JN, Kiss J. Paraventricular nucleus lesions abolish the inhibition of feeding induced by systematic cholecystokinin. Peptides 1985;6:927 48. Higham A, Vaillant C, Yegen B, Thompson DG, Dockray GJ. Relation between cholecystokinin and antral innervation in the control of gastric emptying in the rat. Gut 1997;41:24 49. Tangoku A, Doi R, Chowdhury P, et al. Use of a specific cholecystokinin receptor antagonist (L-364,718) to determine the role of cholecystokinin on feeding and body weight in rats with obstructive jaundice. J Assoc Acad Minor Phys 1992; 2:38 50. Cowley MA, Smart JL, Rubinstein M, et al. Leptin activates anorexigenic POMC neurons through a neural network in the arcuate nucleus. Nature 2001;411:480 51. Rioux KP, Beck PL, Hoppin AG, et al. Differential leptin responses to acute and chronic biliary obstruction in rats. J Hepatol 2000;33:19 52. Muntane-Relat J, Ourlin JC, Domergue J, Maurel P. Differential effects of cytokines on the inducible expression of CYP1A1, CYP1A2 and CYP3A4 in human hepatocytes in primary culture. Hepatology 1995;22:1143 53. Herrera JL. Abnormal liver enzyme levels. The spectrum of causes. Postgrad Med J 1993;93:113 54. McPherson GAD, Benjamin LS, Habib NA, Bowley NB, Blumgart LH. Percutaneous transhepatic drainage in obstructive jaundice: advantages and problems. Br J Surg 1982;69:261 55. Pitt HA, Gomes AS, Lois JF, et al. Does preoperative percutaneous biliary drainage reduce operative risk or increase hospital cost? Ann Surg 1985;201:545 56. Padillo FJ, Gallardo JM, Naranjo A, et al. Changes in the pattern of visceral proteins after internal biliary drainage in patients with obstructive jaundice. Eur J Surg 1999;165:550 57. Denning DA, Ellison EC, Carey LE. Preoperative percutaneous transhepatic biliary decompression lowers operative morbidity in patients with obstructive jaundice. Am J Surg 1981;141:61 58. Norlander A, Kalin B, Sundblad R. Effect of percutaneous transhepatic drainage upon liver function and postoperative mortality. Surg Gynecol Obstet 1982;155: 161