Background Resection of hepatocellular carcinoma is associatedwith high rates of morbidity and mortality. Since intensivenutritional support can reduce the catabolic response and improveprotein synthesis and liver regeneration, we performed a prospectivestudy to investigate whether perioperative nutritional supportcould improve outcome in patients undergoing hepatectomy forhepatocellular carcinoma.
Methods We studied 124 patients undergoing resection of hepatocellularcarcinoma. Sixty-four patients (39 with cirrhosis, 18 with chronicactive hepatitis, and 7 with no associated liver disease) wererandomly assigned to receive perioperative intravenous nutritionalsupport in addition to their oral diet, and 60 patients (33with cirrhosis, 12 with chronic active hepatitis, and 15 withno associated liver disease) were randomly assigned to a controlgroup. The perioperative nutritional therapy consisted of asolution enriched with 35 percent branched-chain amino acids,dextrose, and lipid emulsion (50 percent medium-chain triglycerides)given intravenously for 14 days perioperatively.
Results There was a reduction in the overall postoperative morbidityrate in the perioperative-nutrition group as compared with thecontrol group (34 percent vs. 55 percent; relative risk, 0.66;95 percent confidence interval, 0.45 to 0.96), predominantlybecause of fewer septic complications (17 percent vs. 37 percent;relative risk, 0.57; 95 percent confidence interval, 0.34 to0.96). There were also a reduction in the requirement for diureticagents to control ascites (25 percent vs. 50 percent; relativerisk, 0.57; 95 percent confidence interval, 0.37 to 0.87), lessweight loss after hepatectomy (median loss, 0 kg vs. 1.4 kg;P = 0.01), and less deterioration of liver function as measuredby the change in the rate of clearance of indocyanine green(-2.8 percent vs. -4.8 percent at 20 minutes, P = 0.05). Thesebenefits were seen predominantly in the patients with underlyingcirrhosis who underwent major hepatectomy. There were five deathsduring hospitalization in the perioperative-nutrition group,and nine in the control group (P not significant).
Conclusions Perioperative nutritional support can reduce complicationsafter major hepatectomy for hepatocellular carcinoma associatedwith cirrhosis.
Resection of hepatocellular carcinoma is associated with highrates of morbidity and mortality1,2,3. This is because the majorityof patients have cirrhosis, and hepatectomy causes further deteriorationof liver function4 due to the loss of functioning liver mass.Postoperative sepsis is the other main cause of morbidity andmortality and may be due in part to an enhanced catabolic responseto surgery, increased proteolysis, and decreased immunocompetencein patients with cirrhosis who are already hypercatabolic,5,6malnourished, and immunocompromised7. Since intensive nutritionaltherapy can reduce the net catabolic response to surgery,8 improveprotein synthesis (which is critical for maintaining muscular,respiratory, metabolic, and immunologic function), and promoteliver regeneration,9,10 we performed a prospective study toinvestigate whether perioperative nutritional support couldreduce postoperative morbidity and mortality in patients undergoinghepatectomy for hepatocellular carcinoma.
Methods
Randomization
From September 1990 through June 1993, 150 consecutive patientswhose hepatocellular carcinoma was considered to be resectableon the basis of radiologic studies and hepatic-function testswere randomly assigned to receive either perioperative intravenousnutritional support in addition to their usual oral diet (theperioperative-nutrition group, 75 patients) or no additionaltherapy (the control group, 75 patients). The principal hepatic-functiontest used in this study was the indocyanine green clearancetest. Indocyanine green is a dye that is rapidly eliminatedby a normal liver after intravenous administration. It can beused as a sensitive and dynamic measurement of liver function11.Retention of more than 10 percent of the administered dose ofindocyanine green 15 minutes after intravenous injection isan indication of reduced hepatic functional reserve and hasbeen considered by some surgeons to be a contraindication tomajor hepatectomy12. However, in this study we included suchpatients as surgical candidates.
Sixty-four patients in the perioperative-nutrition group and60 patients in the control group underwent hepatectomy. Theother patients did not undergo hepatectomy because metastaticlesions were discovered in the abdominal cavity. Only the patientsundergoing hepatectomy were studied and their data analyzed.Major hepatectomy was defined as the resection of two or moreliver segments. Minor hepatectomy was defined as the resectionof only one segment. The study protocol was approved by theethics committee of the University of Hong Kong. Informed consentwas obtained from all the patients included in the study.
Treatment
All patients in the perioperative-nutrition group had Broviaccatheters implanted in the superior vena cava by surgical cutdownof the external jugular vein for parenteral nutrition. The parenteralnutrition was given 12 hours a night for seven nights beforehepatectomy and was continued around the clock for seven daysimmediately after hepatectomy. The nutritional therapy consistedof a solution enriched with 35 percent branched-chain aminoacids, at a dosage of approximately 1.5 g of amino acid perkilogram of body weight per day, and dextrose and lipid emulsion(50 percent medium-chain triglycerides) providing 30 kcal perkilogram per day. Vitamins and trace minerals were added tothe parenteral-nutrition fluid daily. The total volume of parenteral-nutritionfluid was limited to 1.75 liters per day.
The patients in the control group had their usual oral dietpreoperatively. In the postoperative period, they received 5percent dextrose and normal saline with a volume and sodiumcontent approximately equal to those of the fluid given to thepatients in the perioperative-nutrition group.
All the patients received 2 g of cefotaxime at the time of theinduction of general anesthesia. Postoperatively, all patientsreceived 2 g of cefotaxime intravenously every 12 hours forthree days and 25 g of albumin intravenously daily for fivedays. They were encouraged to resume oral feeding as soon asbowel function returned. Fluid balance and body weights weremeasured daily to avoid fluid overload.
The surgical treatment was standardized. Hepatectomy was performedby two surgeons using the same technique -- i.e., preliminarycontrol of vascular inflow and outflow, followed by transectionof the liver parenchyma. All resected specimens were examinedhistologically to determine the stage of the disease and todiagnose cirrhosis and chronic active hepatitis.
Assessment
Before randomization, three types of measurement were made.First, an anthropometric assessment included measurements ofbody weight, triceps skin-fold thickness, midarm circumference,and grip strength. Second, a liver biochemical assessment includedmeasurements of serum bilirubin and liver enzymes; prothrombintime; serum concentrations of albumin, transferrin, prealbumin,and retinol-binding protein; plasma glucose; and indocyaninegreen clearance, which was expressed as the percentage of thedose that was retained in the blood 15 and 20 minutes afterthe intravenous administration of dye. Finally, an immunologicassessment included measurements of the response of lymphocytesto stimulation with phytohemagglutinin and serum immunoglobulinlevels.
Serum bilirubin and liver enzymes were measured daily for eightdays after hepatectomy. Serum concentrations of transferrin,prealbumin, and retinol-binding protein were measured on postoperativedays 1, 4, 6, and 8. Anthropometric measurements, the indocyaninegreen clearance test, determinations of serum immunoglobulins,and tests of the lymphocyte response to phytohemagglutinin wererepeated on postoperative day 8.
The assessment of outcome was based on mortality in the hospital,overall postoperative morbidity, changes in anthropometric measurements,and liver and immunologic function. Mortality in the hospitalwas defined as death during the hospital admission for surgery.Postoperative morbidity was determined by independent observersand defined as follows. Pulmonary infection was defined as thepresence of pneumonic or atelectatic changes on radiographsassociated with a positive sputum culture. Wound infection wasdefined as erythema and induration of a wound associated withpurulent discharge that was positive on bacterial culture. Asubphrenic abscess was defined as a collection of pus with orwithout necrotic material associated with a positive bacterialculture. Central-line sepsis was defined as a positive cultureof the catheter tip in the presence of a febrile episode. Pleuraleffusion was considered a complication when the collection offluid caused dyspnea and tapping was required for relief. Asciteswas considered a complication when the accumulation was massive,leading to dyspnea or leakage through the abdominal wound, anda diuretic agent was needed for control. The diuretic agentswere prescribed by medical staff members who were not involvedin the study. Renal failure was defined as an elevation of thepostoperative serum creatinine to more than two times the upperlimit of normal.
Statistical Analysis
The overall rate of postoperative morbidity associated withhepatectomy for hepatocellular carcinoma was 47 percent in HongKong3. A reduction of the rate by half was considered necessaryto indicate the efficacy of perioperative nutritional support.To detect a difference of this magnitude at a level of statisticalsignificance of 0.05 and a power of 0.80, 60 patients were requiredin each group13.
The Mann-Whitney U test was used to compare continuous variables.The chi-square test (with Yates' correction if there were morethan 10 cells) was used to compare discrete variables. All Pvalues of 0.05 or less were considered to indicate statisticalsignificance (by the two-tailed test). Calculations were madewith SPSS computer software (SPSS, Chicago). The important endpoints are presented as relative risks and 95 percent confidenceintervals, which were calculated with Epi Info 6 computer software(World Health Organization, Geneva).
Results
The two groups of patients were similar in terms of age, sex,the amount of weight lost, the results of the preoperative assessment(Table 1), the incidence of underlying cirrhosis, the stage17of disease according to the tumor-node-metastasis (TNM) classificationsystem, and the proportion of patients undergoing major hepatectomy(Table 2). There were more patients in the perioperative-nutritiongroup who retained more than 10 percent of the dose of indocyaninegreen at 15 minutes than in the control group (67 percent vs.47 percent, P = 0.03). Among the patients undergoing major hepatectomy,the proportion who retained more than 10 percent of the doseat 15 minutes was also higher in the perioperative-nutritiongroup (64 percent vs. 43 percent, P = 0.048).
Table 2. Intraoperative Data on Patients Receiving Perioperative Nutrition and Control Patients.
Overall, 22 of 64 patients in the perioperative-nutrition group(34 percent) had postoperative morbidity, as compared with 33of 60 patients in the control group (55 percent; relative risk,0.66; 95 percent confidence interval, 0.45 to 0.96) (Table 3).The difference was mainly due to a reduction in the incidenceof septic complications in the perioperative-nutrition group(11 patients [17 percent] vs. 22 patients [37 percent]; relativerisk, 0.57; 95 percent confidence interval, 0.34 to 0.96). Theneed for diuretic therapy to control ascites was significantlylower in the perioperative-nutrition group than in the controlgroup (16 patients [25 percent] vs. 30 patients [50 percent];relative risk, 0.57; 95 percent confidence interval, 0.37 to0.87). Hospital mortality was 8 percent in the perioperative-nutritiongroup and 15 percent in the control group (P = 0.30).
Table 3. Overall Postoperative Morbidity and Hospital Mortality.
In the postoperative period, there was no significant differencebetween the two groups in prothrombin time, serum bilirubinmeasurements, or liver-enzyme levels, except for serum aspartateaminotransferase (Table 4). Plasma glucose, serum urea, serumtransferrin, serum prealbumin, and serum retinol-binding proteinlevels were significantly higher in the perioperative-nutritiongroup than in the control group on most of the postoperativedays (Table 4).
Table 4. Postoperative Serum Biochemical Data on Patients Receiving Perioperative Nutrition and Control Patients.
On postoperative day 8, the anthropometric measurements weresimilar in the two groups (Table 5). However, a comparison ofweight loss after hepatectomy (measured as the preoperativevalue minus the postoperative value for individual patients)indicated that the patients in the perioperative-nutrition grouplost less weight (median, 0 kg; range, -6.5 to 10) than thepatients in the control group (median, 1.4 kg; range, -1.7 to7.0; P =0.01).
Table 5. Postoperative Data on Patients Receiving Perioperative Nutrition and Control Patients.
Nearly all the patients had a deterioration in indocyanine greenclearance after hepatectomy, but the patients in the perioperative-nutritiongroup had less deterioration than the control patients. Themedian change in indocyanine green retention at 15 minutes (measuredas the preoperative value minus the postoperative value forindividual patients) was -4.4 percent (range, 8.0 to -50.8)in the perioperative-nutrition group and -7.2 percent (range,15.8 to -44.8) in the control group (P = 0.07). The median changein indocyanine green retention at 20 minutes was -2.8 percent(range, 7.3 to -50.5) in the perioperative-nutrition group and-4.8 percent (range, 9.9 to -44.3) in the control group (P =0.05). Measurements of serum immunoglobulins and of the lymphocyteresponse to stimulation with phytohemagglutinin on postoperativeday 8 revealed no significant difference between the two groups(Table 5).
The data were further analyzed to determine whether patientswith underlying chronic liver disease benefited more from perioperativenutritional support than patients with normal livers. Patientswith cirrhosis who received perioperative nutritional supporthad better outcomes than control patients with cirrhosis inthat the overall rate of postoperative morbidity and the needfor diuretic therapy to control ascites were reduced and weightloss was also less severe (Table 6). Patients with no associatedliver disease who received perioperative nutritional supporthad a lower overall rate of postoperative morbidity than controlpatients, but the other benefits were not obvious.
Table 6. Comparison of Outcomes between Subgroups According to Histologic Features of Uninvolved Liver and Extent of Hepatectomy.
Further analyses were performed to determine how the extentof hepatectomy influenced the outcome. Patients who underwentmajor hepatectomy had a lower overall rate of postoperativemorbidity, less deterioration in the clearance of indocyaninegreen, a reduced need for diuretics, and less weight loss afterhepatectomy (Table 6). These benefits were not seen in patientswho underwent minor hepatectomy. An additional analysis of theinfluence of the extent of hepatectomy in the patients withcirrhosis demonstrated only that patients with cirrhosis whounderwent major hepatectomy benefited from perioperative nutritionalsupport; those who underwent minor hepatectomy did not (Table 6).
Two patients had preoperative complications related to nutritionaltherapy (one had catheter sepsis and the other a badly positionedcatheter), and two had postoperative complications (hyperglycemiaand diuresis in the absence of a history of diabetes mellitus).None of the patients died for reasons related to nutritionalsupport.
Discussion
Modern surgical techniques have reduced the operative morbidityand mortality associated with the resection of hepatocellularcarcinoma, but only in patients without underlying liver disease18,19and those with cirrhosis undergoing minor hepatectomy for smalltumors20. When major hepatectomy was carried out in patientswith underlying cirrhosis, the operative mortality ranged from26 to 50 percent18,19,21,22. Major hepatectomy has thereforebeen considered to be contraindicated23,24 in patients withcirrhosis, especially if they retained more than 10 percentof a dose of indocyanine green 15 minutes after intravenousadministration12. In Hong Kong, many patients with hepatocellularcarcinoma present with large tumors associated with cirrhosis,and there is a policy of performing major hepatectomy in thesepatients. We have shown that perioperative nutritional supportoffers a benefit in terms of better protein synthesis, preservedliver function, and reduced morbidity. The benefit was mostevident in patients undergoing major hepatectomy, even thoughthe proportion who retained more than 10 percent of the doseof indocyanine green at 15 minutes was higher than that in thecontrol group.
Perioperative nutritional support has been shown to be usefulin reducing the rate of postoperative complications in severelymalnourished patients25. In our study, the incidence of malnutrition(defined as the loss of more than 10 percent of usual body weight26)was 15 percent, indicating that many patients with normal nutritionalstatus were included. This is because many patients with hepatocellularcarcinoma do not lose substantial amounts of weight at the stagewhen their tumors are resectable. Moreover, hepatectomy is amajor operation that induces a severe catabolic response, evenin patients with normal nutritional status. Therefore, the degreeof malnutrition was not an important consideration in the criteriafor inclusion. Since many of our patients were not cachectic,preoperative nutritional support was given at night to allowpatients to be fully ambulatory during the day and to compensatefor the lack of nutritional intake when they underwent preoperativeinvestigation.
A solution enriched with branched-chain amino acids was chosenfor this study because it is anticatabolic,27 promotes hepatic,muscle, and plasma protein synthesis in patients with chronicliver diseases,28,29 and accelerates liver regeneration in animals30.Since patients with cirrhosis often have glucose intoleranceand insulin resistance,31 branched-chain amino acids may alsobe useful in providing energy to the liver and peripheral tissues,32especially in the immediate postoperative period, when liverfunction is abnormal and oral intake is lacking.
To avert glucose intolerance, a lipid emulsion was includedin the regimen. However, the usual preparation of lipid emulsionconsists of long-chain triglycerides, which are considered inadvisablefor patients with cirrhosis who have impaired synthesis of apoproteinC-II,33 albumin, hepatic triglyceride lipase,34 and carnitine35.Medium-chain triglycerides, which have a reduced dependenceon albumin and apoprotein C-II for breakdown36 and on carnitinefor intracellular metabolism,37 were therefore included. Anadditional advantage of medium-chain triglycerides is that theyare readily oxidized by all body tissues and little is depositedin the liver37. We also demonstrated previously that the mixtureof long-chain and medium-chain triglycerides could be rapidlyeliminated from the blood in patients with cirrhosis38.
There have been few reports of perioperative nutritional supportfor patients undergoing hepatectomy. Reilly et al.39 showedthat postoperative nutritional therapy could improve musclefunction in patients undergoing liver transplantation, allowingearly weaning from respirators. However, Kanematsu et al.40showed that the postoperative administration of a solution enrichedwith branched-chain amino acids did not reduce the incidenceof hepatic coma. In that study, the possible benefits of sucha solution on nutritional variables were not evaluated. In thepresent study, we demonstrated that perioperative nutritionalsupport could lead to less weight loss and to higher serum concentrationsof proteins with a short half-life as well as to higher concentrationsof glucose and urea. The patients' skin-fold thickness, midarmcircumference, and grip strength were not altered by the nutritionalsupport. Probably these measurements were insensitive to short-termchanges. Like Kanematsu et al.,40 we found the incidence offatal hepatic coma to be the same between the two groups ofpatients. We identified the cause of hepatic coma as an errorin surgical technique that led to massive hemorrhage. In thissituation, hepatic coma progressed rapidly and was not reversedby nutritional support.
The reduction in postoperative morbidity in this study did notshorten the hospital stay. Although there was a significantdifference between study groups in the incidence of septic complications,there was no major difference in postoperative immunologic measures.The majority of the septic complications were due to pulmonaryinfection.
In conclusion, perioperative nutritional support in the formof a solution enriched with branched-chain amino acids, dextrose,and medium-chain triglycerides is beneficial in reducing postoperativemorbidity. It is indicated in patients undergoing major hepatectomy,especially when the liver is cirrhotic.
Supported by the Croucher Foundation, Hong Kong.
Source Information
From the Department of Surgery, University of Hong Kong, Queen Mary Hospital, Hong Kong, where reprint requests should be addressed to Professor Fan.
References
Nagao T, Inoue S, Goto S, et al. Hepatic resection for hepatocellular carcinoma: clinical features and long-term prognosis. Ann Surg 1987;205:33-40. [Medline]
Lim RC Jr, Bongard FS. Hepatocellular carcinoma: changing concepts in diagnosis and management. Arch Surg 1984;119:637-642. [Free Full Text]
Choi TK, Lai Edward CS, Fan ST, Mok Francis PT, Wong J. Results of surgical resection for hepatocellular carcinoma. Hepatogastroenterology 1990;37:172-175. [Medline]
Almersjo O, Bengmark S, Hafstrom LO, Olsson R. Enzyme and function changes after extensive liver resection in man. Ann Surg 1969;169:111-119. [Medline]
Shanbhogue RLK, Bistrian BR, Jenkins RL, Jones C, Benotti P, Blackburn GL. Resting energy expenditure in patients with end-stage liver disease and in normal population. JPEN J Parenter Enteral Nutr 1987;11:305-308. [Free Full Text]
Marchesini G, Zoli M, Angiolini A, Dondi C, Bianchi FB, Pisi E. Muscle protein breakdown in liver cirrhosis and the role of altered carbohydrate metabolism. Hepatology 1981;1:294-299. [CrossRef][Medline]
O'Keefe SJ, El-Zayadi AR, Carraher TE, Davis M, Williams R. Malnutrition and immuno-incompetence in patients with liver disease. Lancet 1980;2:615-617. [Medline]
Douglas RG, Shaw JHF. Metabolic response to sepsis and trauma. Br J Surg 1989;76:115-122. [Medline]
Chiba T, Kawai K, Ikenaka K, et al. Effect of an exogenous energy source and amino acids on DNA synthesis in regenerating rat liver. Biochim Biophys Acta 1983;755:420-427. [Medline]
McGowan J, Atryzek V, Fausto N. Effects of protein-deprivation on the regeneration of rat liver after partial hepatectomy. Biochem J 1979;180:25-35. [Medline]
Caesar J, Shaldon S, Chiandussi L, Guevara L, Sherlock S. The use of indocyanine green in the measurement of hepatic blood flow and as a test of hepatic function. Clin Sci 1961;21:43-57.
Hasegawa H, Yamazaki S, Makuuchi M, Shimamura Y. The surgery of hepatocellular carcinoma associated with cirrhosis, with special reference to surgical techniques and pre-, peri-, post-operative care. In: Gozzetti G, Barbara L, Bellusci R, Cavallari A, Gasbarrini G, Mazziotti A, eds. I tumori del fegato. Bologna, Italy: Editrice Compositori, 1985:155-66.
Feinstein AR. Clinical biostatistics. St. Louis: C.V. Mosby, 1977.
Ward RE, Randall HT. Normal blood, plasma, and serum values. In: American College of Surgeons, Committee on Pre and Postoperative Care. Manual of preoperative and postoperative care. 3rd ed. Philadelphia: W.B. Saunders, 1983:757-99.
Fan ST, Lo CM, Lai ECS, Yu WC, Wong J. T lymphocyte function in patients with malignant biliary obstruction. J Gastroenterol Hepatol 1994;9:391-395. [CrossRef][Medline]
The Liver Cancer Study Group of Japan. The general rules for the clinical and pathological study of primary liver cancer. Jpn J Surg 1989;19:98-129. [CrossRef][Medline]
Iwatsuki S, Starzl TE. Personal experience with 411 hepatic resections. Ann Surg 1988;208:421-434. [Medline]
Tsuzuki T, Sugioka A, Ueda M, et al. Hepatic resection for hepatocellular carcinoma. Surgery 1990;107:511-520. [Medline]
Matsumata T, Kanematsu T, Shirabe K, Sonoda T, Furuta T, Sugimachi K. Decreased morbidity and mortality rates in surgical patients with hepatocellular carcinoma. Br J Surg 1990;77:677-680. [Medline]
Gozzetti G, Mazziotti A, Cavallari A, et al. Clinical experience with hepatic resections for hepatocellular carcinoma in patients with cirrhosis. Surg Gynecol Obstet 1988;166:503-510. [Medline]
Nagasue N, Kohno H, Chang YC, et al. Liver resection for hepatocellular carcinoma: results of 229 consecutive patients during 11 years. Ann Surg 1993;217:375-384. [Medline]
Lee CS, Sung JL, Hwang LY, et al. Surgical treatment of 109 patients with symptomatic and asymptomatic hepatocellular carcinoma. Surgery 1986;99:481-490. [Medline]
Smith GW. Techniques of liver resection. In: Shackelford RT, Zuidema GD, eds. Surgery of the alimentary tract. Philadelphia: W.B. Saunders, 1983:447-64.
The Veterans Affairs Total Parenteral Nutrition Cooperative Study Group. Perioperative total parenteral nutrition in surgical patients. N Engl J Med 1991;325:525-532. [Abstract]
Grant JP, Custer PB, Thurlow J. Current techniques of nutritional assessment. Surg Clin North Am 1981;61:437-463. [Medline]
Marchesini G, Zoli M, Dondi C, Bianchi G, Cirulli M, Pisi E. Anticatabolic effect of branched-chain amino acid-enriched solutions in patients with liver cirrhosis. Hepatology 1982;2:420-425. [Medline]
Blackburn GL, Moldawer LL, Usui S, Bothe A Jr, O'Keefe SJ, Bistrian BR. Branched chain amino acid administration and metabolism during starvation, injury, and infection. Surgery 1979;86:307-315. [Medline]
O'Keefe SJD, Ogden J, Dicker J. Enteral and parenteral branched chain amino acid-supplemented nutritional support in patients with encephalopathy due to alcoholic liver disease. JPEN J Parenter Enteral Nutr 1987;11:447-453. [Abstract]
Rigotti P, Peters JC, Tranberg KG, Fischer JE. Effects of amino acid infusions on liver regeneration after partial hepatectomy in the rat. JPEN J Parenter Enteral Nutr 1986;10:17-20. [Free Full Text]
Mezey E. Liver disease and nutrition. Gastroenterology 1978;74:770-783. [Medline]
Muscaritoli M, Cangiano C, Cascino A, et al. Exogenous lipid clearance in compensated liver cirrhosis. JPEN J Parenter Enteral Nutr 1986;10:599-603. [Free Full Text]
Bolzano K, Krempler F, Sandhofer F. "Hepatic" and "extrahepatic" triglyceride lipase activity in post-heparin plasma of normals and patients with cirrhosis of the liver. Horm Metab Res 1975;7:238-241. [CrossRef]
Wolfram G. Die Bedeutung von Karnitin im Fettstoffwechsel. In: Eckart J, Wolfram G, eds. Fett in der parenteralen Ernahrung, 2. Munich, Germany: W. Zuckschwerdt, 1982:28-43.
Deckelbaum RJ, Carpentier Y, Olivecrona T, Moser A. Hydrolysis of medium vs. long chain triglycerides in pure and mixed intravenous lipid emulsions by purified lipoprotein lipases in vitro. Clin Nutr 1986;5:Suppl:54-54.abstract
Bach AC, Babayan VK. Medium-chain triglycerides: an update. Am J Clin Nutr 1982;36:950-962. [Free Full Text]
Fan ST, Wong J. Metabolic clearance of a fat emulsion containing medium-chain triglycerides in cirrhotic patients. JPEN J Parenter Enteral Nutr 1992;16:279-283. [Free Full Text]
Reilly J, Mehta R, Teperman L, et al. Nutritional support after liver transplantation: a randomized prospective study. JPEN J Parenter Enteral Nutr 1990;14:386-391. [Free Full Text]
Kanematsu T, Koyanagi N, Matsumata T, Kitano S, Takenaka K, Sugimachi K. Lack of preventive effect of branched-chain amino acid solution on postoperative hepatic encephalopathy in patients with cirrhosis: a randomized, prospective trial. Surgery 1988;104:482-488. [Medline]
August, D. A., Huhmann, M. B., the American Society for Parenteral and Enteral Nu,
(2009). A.S.P.E.N. Clinical Guidelines: Nutrition Support Therapy During Adult Anticancer Treatment and in Hematopoietic Cell Transplantation. JPEN J Parenter Enteral Nutr
33: 472-500
[Full Text]
Huhmann, M. B., August, D. A.
(2009). Nutrition Support in Surgical Oncology. Nutr Clin Pract
24: 520-526
[Abstract][Full Text]
McClave, S. A., Martindale, R. G., Vanek, V. W., McCarthy, M., Roberts, P., Taylor, B., Ochoa, J. B., Napolitano, L., Cresci, G., the A.S.P.E.N. Board of Directors, , the American College of Critical Care Medicine,
(2009). Guidelines for the Provision and Assessment of Nutrition Support Therapy in the Adult Critically Ill Patient:: Society of Critical Care Medicine (SCCM) and American Society for Parenteral and Enteral Nutrition (A.S.P.E.N.). JPEN J Parenter Enteral Nutr
33: 277-316
[Full Text]
Waitzberg, D. L., Torrinhas, R. S., Jacintho, T. M.
(2006). New Parenteral Lipid Emulsions for Clinical Use. JPEN J Parenter Enteral Nutr
30: 351-367
[Abstract][Full Text]
Shang, E., Weiss, C., Post, S., Kaehler, G.
(2006). The Influence of Early Supplementation of Parenteral Nutrition on Quality of Life and Body Composition in Patients With Advanced Cancer. JPEN J Parenter Enteral Nutr
30: 222-230
[Abstract][Full Text]
Choudry, H. A., Pan, M., Karinch, A. M., Souba, W. W.
(2006). Branched-Chain Amino Acid-Enriched Nutritional Support in Surgical and Cancer Patients. J. Nutr.
136: 314S-318S
[Abstract][Full Text]
Compher, C. W., Spencer, C., Kinosian, B. P.
(2005). Perioperative Parenteral Nutrition: Impact on Morbidity and Mortality in Surgical Patients. Nutr Clin Pract
20: 460-467
[Full Text]
Marchesini, G., Marzocchi, R., Noia, M., Bianchi, G.
(2005). Branched-Chain Amino Acid Supplementation in Patients with Liver Diseases. J. Nutr.
135: 1596S-1601S
[Abstract][Full Text]
Hertl, M., Cosimi, A. B.
(2005). Liver Transplantation for Malignancy. The Oncologist
10: 269-281
[Abstract][Full Text]
Ryder, S D
(2003). Guidelines for the diagnosis and treatment of hepatocellular carcinoma (HCC) in adults. Gut
52: iii1-8
[Full Text]
Chan, S.-C., Liu, C.-L., Lo, C.-M., Lam, C.-M., Poon, R. T.-P., Yuen, W.-K., Fan, S.-T., Wong, J.
(2003). Value of Live Donor Liver Transplantation Experience in Major Hepatectomy for Hepatocellular Carcinoma. Arch Surg
138: 265-271
[Abstract][Full Text]
Barrera, R.
(2002). Nutritional Support in Cancer Patients. JPEN J Parenter Enteral Nutr
26: S63-S71
[Abstract]
Czauderna, P., Mackinlay, G., Perilongo, G., Brown, J., Shafford, E., Aronson, D., Pritchard, J., Chapchap, P., Keeling, J., Plaschkes, J., Otte, J.B.
(2002). Hepatocellular Carcinoma in Children: Results of the First Prospective Study of the International Society of Pediatric Oncology Group. JCO
20: 2798-2804
[Abstract][Full Text]
Kruimel, J. W., Naber, T. H., Adam van der Vliet, J., Carneheim, C., Katan, M. B., Jansen, J. B.
(2001). Parenteral Structured Triglyceride Emulsion Improves Nitrogen Balance and Is Cleared Faster from the Blood in Moderately Catabolic Patients. JPEN J Parenter Enteral Nutr
25: 237-244
[Abstract]
Bistrian, B. R.
(2001). Update on total parenteral nutrition. Am. J. Clin. Nutr.
74: 153-154
[Full Text]
Jeejeebhoy, K. N
(2001). Total parenteral nutrition: potion or poison?. Am. J. Clin. Nutr.
74: 160-163
[Abstract][Full Text]
Maxfield, D., Geehan, D., Way, C. W. V. III
(2001). Perioperative Nutritional Support. Nutr Clin Pract
16: 69-73
van Bokhorst-de van der Schueren, M. A., Quak, J. J, von Blomberg-van der Flier, B M. E, Kuik, D. J, Langendoen, S. I, Snow, G. B, Green, C. J, van Leeuwen, P. A.
(2001). Effect of perioperative nutrition, with and without arginine supplementation, on nutritional status, immune function, postoperative morbidity, and survival in severely malnourished head and neck cancer patients. Am. J. Clin. Nutr.
73: 323-332
[Abstract][Full Text]
Fan, S.-T., Lo, C.-M., Liu, C.-L., Yong, B.-H., Chan, J. K.-F., Ng, I. O.-L.
(2000). Safety of Donors in Live Donor Liver Transplantation Using Right Lobe Grafts. Arch Surg
135: 336-340
[Abstract][Full Text]
Gianotti, L., Braga, M., Fortis, C., Soldini, L., Vignali, A., Colombo, S., Radaelli, G., Di Carlo, V.
(1999). A Prospective, Randomized Clinical Trial on Perioperative Feeding With an Arginine-, Omega-3 Fatty Acid-, and RNA-Enriched Enteral Diet: Effect on Host Response and Nutritional Status. JPEN J Parenter Enteral Nutr
23: 314-320
[Abstract]
Fan, S.-T., Ng, I. O. L., Poon, R. T. P., Lo, C.-M., Liu, C.-L., Wong, J.
(1999). Hepatectomy for Hepatocellular Carcinoma: The Surgeon's Role in Long-term Survival. Arch Surg
134: 1124-1130
[Abstract][Full Text]
Torzilli, G., Makuuchi, M., Inoue, K., Takayama, T., Sakamoto, Y., Sugawara, Y., Kubota, K., Zucchi, A.
(1999). No-Mortality Liver Resection for Hepatocellular Carcinoma in Cirrhotic and Noncirrhotic Patients: Is There a Way? A Prospective Analysis of Our Approach. Arch Surg
134: 984-992
[Abstract][Full Text]
McClave, S. A., Snider, H. L., Spain, D. A.
(1999). Preoperative Issues in Clinical Nutrition. Chest
115
: 64S-70S
[Abstract][Full Text]
Heyland, D. K., MacDonald, S., Keefe, L., Drover, J. W.
(1998). Total Parenteral Nutrition in the Critically Ill Patient: A Meta-analysis. JAMA
280: 2013-2019
[Abstract][Full Text]
Reynolds, J. V., Kanwar, S., Welsh, F. K.S., Windsor, A. C.J., Murchan, P., Barclay, G. R., Guillou, P. J.
(1997). Does the Route of Feeding Modify Gut Barrier Function and Clinical Outcome in Patients After Major Upper Gastrointestinal Surgery?. JPEN J Parenter Enteral Nutr
21: 196-201
[Abstract]
Klein, S., Kinney, J., Jeejeebhoy, K., Alpers, D., Hellerstein, M., Murray, M., Twomey, P.
(1997). Nutrition Support in Clinical Practice: Review of Published Data and Recommendations for Future Research Directions: Summary of a Conference Sponsored by the National Institutes of Health, American Society for Parenteral and Enteral Nutrition, and American Society for Clinical Nutrition. JPEN J Parenter Enteral Nutr
21: 133-156
[Abstract]
Souba, W. W.
(1997). Nutritional Support. NEJM
336: 41-48
[Full Text]
Wolfe, B. M., Mathiesen, K. A.
(1997). Clinical Practice Guidelines in Nutrition Support: Can They Be Based on Randomized Clinical Trials?. JPEN J Parenter Enteral Nutr
21: 1-6
Fischer, J. E.
(1996). 1996 Jonathan E. Rhoads Lecture. Mechanism, Mechanism, Mechanism. JPEN J Parenter Enteral Nutr
20: 319-324
Welsh, F. K.S., Farmery, S. M., Ramsden, C., Guillou, P. J., Reynolds, J. V.
(1996). Reversible Impairment in Monocyte Major Histocompatibility Complex Class II Expression in Malnourished Surgical Patients. JPEN J Parenter Enteral Nutr
20: 344-348
[Abstract]
Mealy, K., Tessari, P., Barazzoni, R., Zanetti, M., Fan, S.-T.
(1995). Perioperative Nutritional Support. NEJM
332: 1173-1173
[Full Text]
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