Biliary drainage in jaundiced rats

Biliary drainage in jaundiced rats

544 SELECTED SUMMARIES (;IISTKO~;N’I‘~K(~LO(;Y some 5 abnormality is recessive and is only expressed concomitantly with the development of cancer...

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544

SELECTED

SUMMARIES

(;IISTKO~;N’I‘~K(~LO(;Y

some 5 abnormality

is recessive and is only expressed concomitantly with the development of cancer. Thus, the polyps from FPC “patients do not yet show the recessive change is consistent with data using GGPD markers which suggested that polyps were not clonal” (Science 1983;221:951-3). The data in the Solomon article are less convincing than the data on FPC. However, because of its greater potential impact, it rightly received the publicity. Solomon et al.. in evaluating chromosomal 5 defects in sporadic colon cancer tissue, did not use the cDNA probe they used in evaluating the lymphocytes of families of FPC. That probe. Cllpll. was used to more preciseI! localize the gene defect in FPC. In the case of inherited syndromes. one might postulate that the genetic defect would be consistent and specifically localized on the chromosome so that gene markers near the FPC gene would cosegregate with the phenotype. The cDNA probe Cllpll did not identify the gene for FPC but did define the area on chromosome 5 ~vhere it most likely c:ontrol of c:r,ltrn to growth resided. If the FPC gene is critical epithelium, then one can assume that colon opithelia that undergo malignant transformation would show a number of different defects in chromosome 5. any of which would have had to alter the expression of the gene for FPC. the presumed growth r.ontrol gene for colon epithelium. Thus, the work by Solomon et al. focused on markers that were more likely to detect any defect in the long arm of chromosome 5. They felt secure in stating that Zoo/,, of sporadic colon cancers showed deletion of chromosome 5, and less secure in stating the possibility that this may he as high as 40°h,. This work has opened up new and exciting approaches to the biology of colon cancer. It may also establish a more c:ritical marker for early cancerous changes. Is it possible that polyps. or tissue from ulcerative colitis, when tested for Lhromosome 5 abnormalities. would more accurately detect early cancer and indicate the need for colectomy? When the gene for FPC: is defined and it does turn out to code for an “inhibitor” specific: for colon epithelial growth (an important concept in itself]. will molecular biologv be able to synthesize new inhibitors to he used therapeuticallv? Stav tuned.

group 4. Animals that died after biliary duct ligation or the drainage procedures in the other groups were excluded from the end results. Body weight was initially the same for the animals in all four groups. However, those animals with external biliary drainage weighed less at the time of cecal ligation and perforation despite daily replacement of bile loss with subcutaneous saline injections. Serum albumin concentrations were the same for all groups initially, then fell after bile duct ligation. There was no difference in serum albumin level between the internal and external drainage group. The albumin values for both drainage groups were significantly lower than the sham group (p
BILIARY DRAINAGE

Vol. 94. No. 2

salts

are

absent

from

the

intestinal

tract.

IN JAUNDICED RATS

Goumu DJ, Coelho

JCLJ, Schlegel IF, Li YF, Moody FG of Surgery, University of Texas Medical School, Houston, Texas, and Department of Surgery, St. Annadal Hospital, University of Limburg, Maastricht, the Netherlands) The effect of preoperative internal and external biliary drainage on mortality of jaundiced rats. Arch Surg 1987;122:731-4. (Department

This study involved Sprague-Dawley rats weighing between 175 and 220 g. The animals were separated into four groups. Group 1 consisted of 15 animals who underwent bile duct ligation, followed 2 wk later by cecal ligation and puncture. Group 2 consisted of 16 animals who had bile duct ligation with a subsequent internal biliary drainage procedure, followed 2 wk later by cecal ligation and puncture. Group 3 consisted of 11 animals who had the same procedures as the animals in group 2, except the biliary drainage procedure was external rather than interwho had a sham nal. Group 4 consisted of 18 animals operation followed 2 wk later by cecal ligation and punt:ture. There was no mortality after the sham operation on

Comment. Even with substantial improvements in anesthesia. surgical techniques, and postoperative management. major surgical procedures in the presonco of hiliary obstruction and jaundice still have a high mortality rate. In 1935, A. 0. Whipple (Ann Surg 11135:102:7fi:(-711) tlesc.ribtrtl initial biliary bypass surgery and suhsrquent pa~~~:re~~ticoduo~l(~neLtomy. For years this two-stage surgical approach to malignant hiliary obstruction ~vas used. A rotrospec.tive study of this twostage procedure was reported by IMaki et al. (Arch Surg 1966;92: 825~3:3), with a fall in mortality from 50% to f%%. In 1978. Nakayama at Chiba tlniversiiy in Japan ((;astroentt~rology 1978:74:554-Y) described an effective pcm:utant:ous technique for preoperative biliary drainage by \yhich operative mortality was signifif:antly redurxd from 28 ‘;+,to 8% in patients with malignant hiliary obstruction. when compared to historical cnntro1s. Numf!rous

cher

retrosptxtive

trials

oi preoperative

percutane-

drainage (Am 1 Surg 1981;14 1:flG.i. Surg Dyneco1 Ohstet 1982:155:161-6) have consistrntl~~ tlemonstrated in]provement in operative mortality in the drainage patients. with a low I”oc”‘lurf:-associated morbidity and mortalitv. ‘I’hese imprrssivc: figures h,lvo not held up to prospective. randomized twaluatirrtls. One of thr first prospcctiw trials was clout: at the Hnmmrrsmith Hospital Hepatobiliary lJnit in 1982 (LanLet 1982:

ous

transhpatic.

February

1~88

SKLECTEI)

ii:896-9). This single-arm study of 37 patients, 35 of whom had malignant obstruction, demonstrated a drainage-related morbidity of 54% and a drainage-related mortality of 13.5°Ar. Other prospec:tive trials, of preoperative percutaneous drainage (Br J Surg 1984;71:3’71-5, Ann Surg 1985;201:545-5, Br J Surg 1982;69:2614) confirmed the lack of postoperative mortality reduction and the high drainage-related complication rate. Reasons for the high morbidity associated with percutaneous drainage include the manipulation of catheters through the peritoneal cavity and hepatic parenchyma, with an inherent risk of bile peritonitis and injury to intrapleural and vascular structures. Advocates of endoscopically placed biliary stents point out their high success rate (80%-90%)) and low morbidity and mortality in nonrandomized selected patients (Am J Gastroenterol 1986;81: 634-9). Another study (Radiology 1986;158:195-7) demonstrated similar placement success for endoscopic and percutaneous biliary drainage, but the endoscopic group had a lower complication rate and mortality. A randomized prospective trial of endoscopic versus percutaneous biliary drainage has recently been completed in England, but the results, which are said to favor the endoscopic route. have been published only in abstract form (Gut 1985;26:A.1135). Perhaps another reason for the lack of demonstrable mortality benefit for the percutaneous preoperative biliary drainage has less to do with procedure-related morbidity and more with the fact that the bile is usually drained externally and away from the intestinal tract. The present study lends support to this concept. Bailey, in a study of both humans and rats (Br J Surg 1976;63:774in the jaundiced human subjects 8) suggested that endotoxemia

accounted for decreased renal function postoperatively, as measured by creatinine clearance. In the animal studies that followed, he demorlstrated that the lack of normal concentrations of bile salts in the intestine allowed the absorption of endotoxin, whic:h might be prevented by feeding patients bile salts. The method of stent placement, whether endoscopic or percutaneous. may have less to do with postoperative mortality than with whether the bile is drained externally or internally. The prospective randomized trials of preoperative percutaneous biliary dr,;linage did not stratify for external or internal drainage when comparing morbidity and mortality data. In a recent, prospective randomized study from Australia (Surgery 1985;97:64161 an attempt was made to internalize all of the percutaneous stents. Those patients who were drained internally had fewer complications than those who went directly to surgery (p <0.02). This advantage was reduced when the morbidity of the percutaneous procedure was accounted for in the analysis. Endoscopic: placement of biliary stents would appear to be ideal in that the morbidity of the percutaneous technique is avoided and internal drainage is established by the very nature of the procedure. Whether or not the endoscopic approach will actually prove to be better than the percutaneous technique still awaits publication of the clinical trials. K.(:. KIJKTZ, b1.D.

Reply. As summarized by Kurtz, our study showed a significant reduction in mortality by internal biliary drainage: however, no reduction was seen after external drainage. Lack of bile salts with persistent endotoxemia has been suggested. Therefore, in a second study (Am J Surg 1986;151:476-80), we evaluated whether systemic and portal endotoxemia occurred in rats with obstructive jaundice, and if there was a change in systemic and portal endotoxemia after relief of the obstruction by internal and external biliary drainage. Endotoxemia was increased after bile duct ligation compared with control values. The incidence of systemic and portal endotoxemia was significantly reduced after internal drainage (p -CO.OOl). A significantly higher incidence of portal

SLIMM.ZKIES

545

(86%) and systemic (57%) endotoxemia was found after external drainage. The persistence of endotoxemia after external drainage, when serum bilirubin levels returned to normal units, indicates that bile flow is important in controlling eodotoxemia during preoperative biliary drainage. These results suggest that the systemic endotoxemia observed after relief of obstruction by external drainage may contribute to the increased mortality. In 1982, Hunt (Am J Surg 1982:144:325-g) already reported that patients with endotoxemia carry a poor prognosis. Furthermore. bile salts, especially sodium deoxycholate, have been shown to reduce endotoxemia (Br J Surg 1983;70:590-5) and also to improve wound healing (Surg Gynecol Obstet 1984:159:207-9). Oral lactulose has recently been reported to have the same effects (Pain et al.. Br J Surg 1986;73:775-8). These authors suggest that lactulose or bile salts could be effective agents in reducing endotoxin-related complications and lead to a reduction of mortality. It is likely, however, that morbidity and mortality in obstructive jaundice are not only endotoxin-related. Obstructive jaundice is also associated with changes in nutritional status. in other studies (Am J Clin Nutr 1986;44:362-9) we found persistent hypoalbuminemia in rats with obstructive jaundice, despite a normal daily food intake. A second advantage of internal biliary drainage, as shown in that study, is improvement of these nutritional indices, which could also contribute to reduction of morbidity and mortality. The recently published randomized trial of percutaneous versus endoscopic drainage (Lancet 1987:ii:57--63) expressed, indeed, favor for the endoscopic route and strongly supported endoscopic placement of stents as first choice. Preoperative percutaneous drainage cannot be recommended any more. The above-mentioned data, however, justify a clinical randomized trial of preoperative endoscopic drainage to definitively access the role of internal biliary drainage. Theoretically, preoperative biliary drainage by endoscopic sphincterotomy for ampullary tumors should be the ideal trial, as any influence of stents can be excluded.

CHRONIC ETHANOL FEEDING DECREASES MITOCHONDRIAL GLUTATHIONE IN RATS Fernandez-Checn \C, Ookhtens M, Kaplowitz N [Liver Research Laboratory, Wadsworth Veterans Administration Hospital Center, and UCLA School of Medicine, Los Angeles, California) Effect of chronic ethanol feeding on rat hepatocytic glutathione. Compartmentation, efflux, and response to incubation with ethanol. J Clin Invest 1987;80: 57-62

(July).

Glutathione (GSH), the little ubiquitous tripeptide present in large amounts in hepatocytes, serves to protect cells from the attack of free radicals and the consequences of lipid peroxidation, to name but a few of its putative functions. Its protective action may result from its capacity to inactivate free radicals or possibly from its role as a cosubstrate for lipid peroxide-reducing GSH peroxidase. Both pathways lead to the oxidation of GSH to glutathione disulfide. Glutathione levels have been reported to increase, decrease, or not change at all in the liver after chronic exposure to ethanol. Because GSH is present in both cytoplasmic and mitochondrial pools, and mitochondria may be selectively injured by exposure to ethanol, the