Effect of internal biliary drainage on plasma levels of endotoxin,cytokines, and C-reactive protein in patients with obstructive jaundice

Preoperative biliary drainage may improve the cytokine and acute-phase response derangements observed in patients with obstructive jaundice. We conducted a prospective longitudinal, before-after trial in our 600-bed teaching hospital. Twenty-four patients with obstructive jaundice were investigated, 11 with benign obstruction and 13 with malignant disease. Endoscopic internal biliary drainage was performed in all patients (7 by papillotomy and 17 by endoprostheses). Endotoxin, tumor necrosis factor alpha (TNF-a), interleukin-6 (IL-6), nitric oxide production, and C-reactive protein (CRP) were determined at admission and on days 2 and 7 after internal biliary drainage was accomplished. Bile cultures were obtained before and at the time of drainage. Endotoxin, IL-6, TNF-a, and CRP were significantly higher in patients with cancer. After internal drainage, endotoxin (11.4 vs. 2 EU/L; p <0.05), TNF-a (87.5 vs. 48 pg/ml; p = 0.03), and IL-6 (324 vs. 232 pg/ml; p <0.05) plasma levels decreased significantly in the early postdrainage period in patients with cancer. Endotoxin, cytokines, as well as the CRP plasma values, however, increased again on day 7 after drainage. This trend was less marked in patients with benign obstruction. Patients with positive bile cultures after drainage displayed higher levels of CRP (115 vs. 62 mg/L; p = 0.03), IL-6 (598 vs. 330 pg/ml; p = 0.04), and endotoxin (10.6 vs. 4.8 EU/L; p = 0.02) than those with negative bile cultures. Biliary tract obstruction is associated with an increase in endotoxin levels, a positive acute-phase response, and plasma cytokine elevation. After biliary drainage a transitory improvement of these alterations was observed, although values remained high 1 week postdrainage. These findings were associated with positive bile cultures.     

Complement in local biliary tract defense: dissociation between bile complement and acute phase reactants in cholecystitis

Biliary complement concentrations and activity are lower in patients with infected bile than in those with sterile bile in cholecystitis. Plasma complement is increased during the acute phase response to inflammation. To determine whether low biliary complement in infected bile is a specific response to biliary tract infection or part of a general systemic reaction, we analyzed bile complement proteins (C3 and C4) and activity (C4H50) and acute phase reactants fibronectin, C-reactive protein, and alpha 1-antitrypsin concentrations in acute and chronic cholecystitis. Results were correlated with bile cultures and gallbladder histology using the Wilcoxon rank sum test. While biliary C3, C4, and C4H50 were significantly lower in infected bile than in sterile bile, none of the acute phase reactants were different. The biliary acute phase reactants were all significantly higher in acute cholecystitis than in chronic disease, but there was no difference in the biliary C3, C4, or C4H50 levels. There was no clear relationship between plasma levels of complement and the acute phase reactants. The dissociation between biliary complement and acute phase reactants indicates that bile complement is not a reflection of a systemic reaction to inflammation. We propose that biliary complement is a specific host defense mechanism against bacterial infection in the biliary tract.     

Bacterial contamination of the biliary tree after choledochostomy

Secondary exogenous contamination of bile after choledochostomy could be an important cause of long-term morbidity if infection persists after removal of the T tube. Surprisingly, documentation of the frequency of conversion of sterile to infected bile after choledochostomy has rarely been recorded. Patients undergoing exploration and T-tube drainage of the common bile duct between July 1966 and January 1975, in whom intraoperative and postoperative cultures of bile were available, were studied. Postoperative cultures were obtained from five to forty days after operation. Of ninety-five patients available for study, contamination developed postoperatively in previously sterile bile in 44 per cent. The common duct bile contained bacteria at operation in 42 per cent and remained sterile throughout in 14 per cent. The most common secondary contaminants were klebsiella group and Escherichia coli. The fate of the contaminating organisms in a biliary tree without anatomic abnormalities is unknown. Two cases are presented which suggest that persistent infection may linger in the biliary tree for many years and give rise to pigment calculi. Since bacterial cannot be eradicated so long as a foreign body remains in the common duct and because such bacteria may cause symptoms even in an anatomically normal biliary tree, we suggest that a closed system of biliary drainage be employed and that appropriate antibiotic therapy be instituted for seven to ten days after removal of the T tubes.     

Altered Kupffer cell function in biliary obstruction

BACKGROUND: An altered Kupffer cell (KC) response is thought to be responsible for the characteristic phenotype observed after biliary obstruction: a phenotype marked by a defect in the hepatic reticuloendothelial system and a hypersensitivity to endotoxin. Few studies, however, have directly examined KC function. We have sought to define the specific alterations in function and phenotype that occur in the KC after biliary obstruction. METHODS: KCs were isolated from female C57BL/6 mice 4 days after a sham or common bile duct ligation (CBDL) operation. Phagocytosis, oxidative burst potential, and intracellular bacterial killing were measured as markers of reticuloendothelial system function. The KC response to endotoxin was assessed by measuring tumor necrosis factor alpha and interleukin 6 levels in the media after stimulation with lipopolysaccharide (LPS) or with LPS plus LPS-binding protein (LBP). RESULTS: CBDL KCs demonstrated a significant increase in phagocytic ability and significantly decreased baseline oxidative stress, compared with Shams. The oxidative burst potential, however, was equivalent or higher for CBDL KCs. CBDL KCs also demonstrated increased numbers of viable intracellular bacteria after infection; however, it is unclear if this finding represents impaired intracellular bacterial killing or increased phagocytosis of bacteria. With respect to the KC response to endotoxin, CBDL KCs were found to be less sensitive to the stimulatory effects of LPS alone but were exquisitely sensitive to the effects of LBP. LBP levels were found to be significantly elevated in CBDL animals, and CBDL KCs demonstrated a dose-dependent, exaggerated tumor necrosis factor alpha and interleukin 6 response to LPS administered with LBP. CONCLUSIONS: KC function is clearly altered after biliary obstruction. Phagocytic ability is actually increased, although the ability of CBDL KCs to kill bacteria within the phagosome remains ill defined. CBDL KCs are exquisitely sensitive to the effects of LBP, and LBP levels are elevated after biliary obstruction. LBP may be responsible for the increased proinflammatory response observed after endotoxin challenge in animals with biliary obstruction.     

胆汁转流性外引流术对恶性梗阻性黄疸血内毒素水平的影响

目的 :探讨外引流术体外转流胆汁对恶性梗阻性黄疸病人血内毒素水平的影响。方法 :对 14例肿瘤手术不能切除的恶性梗阻性黄疸病人行胆汁转流性外引流术 ,与同期施行的 15例内引流术、2 0例外引流术病人进行手术前后外周血内毒素水平比较。结果 :术前 3组内毒素水平差别无显著性意义 (P>0 .0 5 )。单纯外引流组手术后内毒素水平略高于术前 (P >0 .0 5 ) ;内引流组术后第 2天内毒素水平反而高于术前 (P <0 .0 5 ) ,第 7天、第 14天显著降低 (P <0 .0 5 ,P <0 .0 1) ;体外转流组术后内毒素水平逐渐降低 ,与内引流术组变化基本相同。结论 :胆汁转流性外引流术可降低恶性梗阻性黄疸病人外周血内毒素水平。     

Single-daily-dose treatment of ceftriaxone for biliary tract infections and bacterial counts in bile

To evaluate the effects of ceftriaxone (CTRX) administered once daily, the biliary concentration of CTRX and daily changes in the bacterial count in bile from an indwelling T-tube were measured concomitantly. The effects on prophylaxis of postoperative infections after biliary tract surgery were also examined mainly due to clinical symptoms. The biliary CTRX levels increased rapidly and were sustained as high as 92.5-219 micrograms/ml in all patients even 24 hours after 2 g of CTRX was infused intravenously once daily. Five of 7 patients whose bile samples were positive for bacteria showed high CTRX levels in bile and almost no bacteria present after treatment. CTRX-sensitive bacteria eliminated 1 or 2 hours after the administration in response to the increase of biliary CTRX levels. The changes in bacteria count of bile may be closely related to CTRX antibiotic activity. As an antibiotic prophylaxis, other 18 patients with biliary diseases received intravenous infusion of 2 g of CTRX once daily for 5-7 days (mean 5.9 days). Thus, once-daily dose treatment of CTRX 2 g may have antibiotic effects on biliary infection and postoperative prophylaxis of biliary infections and it is indicated that the prolonged biliary levels of CTRX are essential for its efficacy.     

Pancreaticoduodenectomy for periampullary malignancies: the effect of bile colonization on the postoperative outcome

Objectives The presence of bacteria in the bile of patients undergoing biliary tract surgery has been proposed as associated to an increased incidence of postoperative complications. The present study was designed to determine whether colonization of the bile has an adverse effect in terms of postoperative infectious or noninfectious complications and mortality in a homogenous population of patients suffering from periampullary region malignancies, who all underwent resectional (curative) procedures. Materials and methods Between January 1997 and December 2002, 115 patients (n = 115) suffering from periampullary region malignancies underwent resectional procedures. Fifty-two of the above patients were referred having undergone preoperative internal biliary drainage. During the operation, bile was routinely isolated from the common bile duct and was sent for culture and sensitivity. Based on the bile culture results, the patients were divided in sterile and colonized group and were retrospectively compared in terms of postoperative outcome and mortality. Results Of the 115 bile cultures, 67 were colonized with bacteria and 48 were sterile. Postoperatively, 40 patients developed 35 noninfectious and 21 infectious complications. Univariate analysis did not disclose statistically significant differences in overall, noninfectious or infectious morbidity and mortality between the two groups of patients. Although not statistically significant, a higher incidence (22 vs 10%) of postoperative leaks in the colonized group of patients was noticed. Multiple regression analysis disclosed that colonized bile was independently related to the advanced age, preoperative biliary drainage presence, elevated preoperative serum bilirubin levels and low preoperative serum albumin levels but did not predispose to an increased postoperative morbidity, mortality, or reoperation rate. Conclusion The present study did not conclude in any statistically significant differences in the postoperative infectious and noninfectious morbidity as well as mortality, between colonized and sterile groups of patients who underwent resectional procedures for malignancies of the periampullary region. Although internal biliary drainage introduces microorganisms into the biliary tree, this colonization does not increase the risk of either infectious or noninfectious complications or postoperative death. Thus, the likelihood of bacterobilia should not contraindicate the procedure in selected cases.     

不同胆汁引流方式对梗阻性黄疸兔血清内毒素与免疫功能的影响

目的:探讨不同胆汁引流方式对梗阻性黄疸兔血清内毒素与免疫功能的影响。方法:将36只新西兰白兔随机均分为假手术组、外引流组、内引流组。外引流组与内引流组先建立可逆型梗阻性黄疸模型,7 d后解除梗阻,分别行胆汁外引流与内引流;假手术组按相同时间间隔行2次假手术。各组分别于造模前、造模后7 d、引流术后7 d采血,检测肝功能指标、血清内毒素水平、血中CD4+CD25+调节性T细胞的比例。结果:假手术组各时间点各项指标均无明显变化(均P0.05);造模后7 d,外引流组与内引流组血清胆红素、转氨酶、内毒素水平均较造模前明显升高,血CD4+CD25+调节性T细胞比例较造模前明显降低(均P0.05);行引流术7 d后,外引流组与内引流组肝功能指标、内毒素水平、CD4+CD25+调节性T细胞比例均较造模后7 d明显恢复,但内引流组后两项指标的恢复程度均明显优于外引流组(均P0.05)。结论:胆汁内引流较胆汁外引流更有利于梗阻性黄疸内毒素清除与机体免疫功能快速恢复。     

Endotoxemia during percutaneous manipulation of the obstructed biliary tree

Fourteen patients undergoing percutaneous biliary manipulation were studied on 21 occasions. Using a chromogenic limulus-based assay technique, peripheral endotoxin concentration prior to the procedure was found to be 6.1 +/- 9 pg/ml, increasing to 30.7 +/- 26 pg/ml after the procedure (p less than 0.001). Fourteen of 21 bile cultures and only 1 of 21 blood cultures drawn during the procedure were positive for bacterial growth. There was a clinically modest but statistically significant decrease in blood pressure (p less than 0.05), an increase in temperature (p less than 0.01), and an increase in creatinine concentration (p less than 0.05) before and after biliary manipulation. The presence of infected bile and the preprocedure bilirubin level predicted development of endotoxemia.     

胆道感染与胆汁粘度变化关系的探讨

目的了解胆道感染时胆汁粘度的动态变化,为胆结石成因提供线索,为临床提供更合理的治疗计划。方法３０例Ｔ管引流的连续病员,用ＮＸ３型毛细玻管粘度计测定相对粘度,并对胆汁作需氧、厌氧培养和菌落计数。结果有菌胆汁粘度明显高于无菌胆汁,但与细菌量的多少无关。有菌胆汁中粘度明显大于术后各天,后随引流时间而逐渐下降,至６天后趋于稳定并接近正常。有菌胆汁菌落量在术后２周内不随引流时间增加而变化,直到术后第３周菌落量才有显著减少。结论有菌胆汁粘度升高,但细菌并非直接因素。胆汁中的细菌和粘度升高在胆管结石形成中起协同作用。Ｔ管引流能有效地降低胆汁粘度,而胆汁中细菌量在引流术后第３周才有显著减少,临床２周时拨除Ｔ管细菌可潜伏下来,对胆管炎和胆管结石的复发可能起作用。     

Biliary tract surgery: a bacteriologic and epidemiologic study

The sources and routes of postoperative wound infections were prospectively studied in 440 patients undergoing biliary tract surgery. The overall infection rate was 7.3%. Specimens for culture were taken peroperatively from bile, liver bed and subcutaneous fat in 402 patients and also from skin in 64. Of the 126 patients with positive bile culture (31%), all but one had bacteria in the other intraoperative cultures, with high counts of bile bacteria in liver bed and transfer of such bacteria to subcutaneous fat in 81.2%. The wound infection rate in this group was 12.8%. Of the 276 patients with sterile bile, more than 90% had bacteria in the other intraoperative cultures. The degree of contamination was low, with dominance of typical skin bacteria, and the group wound infection rate was 3.2%. In 19 postoperative wound infections intraoperative cultures were available for comparison. Eleven of these infections were classified as endogenous, six as exogenous and two as of uncertain origin. S. aureus was uncommon in bile and intraoperative wound cultures, but was almost as common as E. coli in the etiology of postoperative wound infections, indicating high pathogenicity.     

Routine drainage in cholecystectomy. A bacteriologic and clinical assessment.

A prospective study was carried out to determine the possible role of exogenous and endogenous bacteria in the development of postoperative complications in patients in whom drainage was routinely employed after cholecystectomy. In 100 patients undergoing cholecystectomy because of cholelithiasis, cultures were made of specimens taken from the bile during operation and from the drains. Bile cultures were positive in thirty-eight patients. Drain cultures were positive in thirty-five patients, with most of the bacteria cultured being from an exogenous source (in most cases staphylococcus). The rate of postoperative complications was found to be significantly higher in the group with positive bile cultures (of endogenous origin) than in the group with positive drain cultures (of exogenous origin) or sterile cultures. In the patients with positive bile cultures, the rate of wound infection was 31 per cent, whereas in those with positive drain cultures it was 5.7 per cent, and in those with sterile drains only 4 per cent. These findings indicate that if the bile is not infected, the risk of wound infection is considerably reduced and that the bacteria of exogenous source do not play a prominent role in the development of postoperative complications. In consideration of this as well as the fact that the use of a drain may obviate the need for reexploration in patients in whom there is postoperative leakage of bile or blood, routine drainage should not be rejected categorically in “clean” abdominal operations.     

Experimental study on the development of endotoxemia in biliary tract infection with special reference to lymphatic pathway at controlled biliary duct pressure

A study was made on the pathway of the endotoxin from the biliary tract into the circulation, using adult mongrel dogs divided into 10 groups primarily with or without thoracic duct drainage. The biliary duct pressure level of 25, 35, and 55 cm saline was maintained by infusing physiological saline into the bile duct. Each level was maintained for a 10-minute period following the intrabiliary infusion of endotoxin 10 mcg/kg. The endotoxin level in arterial and portal blood and in thoracic lymph increased with increment of biliary duct pressure. The endotoxin level in the thoracic lymph was more than 10 times higher than that in blood. At 35 and 55 cm saline of biliary duct pressure, the groups with or without thoracic lymph drainage did not show any significant difference in blood endotoxin level, or moreover, endotoxin shock developed in each group. These findings imply that at high biliary pressure such as 35 or 55 cm saline, endotoxin in the bile duct directly appears in the sinusoid. At low biliary pressure such as 25 cm saline, endotoxin was detected only in thoracic lymph and endotoxemia did not develop.     

Does probiotics administration decrease serum endotoxin levels in infants?

PURPOSE: The aim of this study was to examine whether administration of probiotics to infants can change the ratio of intestinal flora and thereby decrease serum endotoxin produced by potentially pathogenic microorganisms. METHODS: Nine infants including five with of biliary atresia, two with omphalocele, one each with Hirschsprung's disease and imperforate anus were studied. All patients were stable, and no antibiotics were given during this study. A probiotic mixture consisting of Streptococcus faecalis, Clostridium butyricum and Bacillus mesentericus was administered orally to each infant at 2 g/day for 2 weeks. Fecal aerobic and anaerobic bacterial cultures, serum endotoxin level, and other biochemical parameters were examined. RESULTS: In fecal cultures, anaerobic bacteria including Bifidobacterium increased significantly whereas Escherichia coli, Streptococcus, and Klebsiella tended to decrease. The ratio of anaerobic to aerobic bacteria increased five times as a result of administration of probiotics, and serum endotoxin levels decreased. CONCLUSIONS: Probiotics affect intestinal bacterial flora by increasing anaerobic bacteria and decreasing the population of potentially pathogenic microorganisms. A decrease in luminal endotoxin may result in less endotoxin translocation or bacterial translocation.     

Anorexia and the effect of internal biliary drainage on food intake in patients with obstructive jaundice

BACKGROUND: Anorexia is a frequent finding in patients with biliary obstruction (BO). This study investigates the role of biochemical and hormonal factors in the pathogenesis of reduced food intake in BO and the effects of internal biliary drainage. STUDY DESIGN: Sixty-two patients with BO were prospectively investigated. Transaminases, amylase, cholecystokinin, secretin, bile acids, tumor necrosis factor-alpha, and endotoxin were determined at admission. Caloric intake was quantified by a controlled diet. In a subset of 27 patients, studies were repeated after internal biliary drainage. RESULTS: Sixty-six percent of patients had spontaneous food intakes below the estimated caloric requirements. Serum bilirubin, alkaline phosphatase, and cholecystokinin plasma levels were independent predictor factors for calorie intake (p = 0.0001). After internal biliary drainage, cholestasis parameters and cholecystokinin concentrations decreased significantly; this was associated with an improvement of spontaneous food intake in both benign and malignant biliary obstruction (p < 0.01 and p < 0.05, respectively). CONCLUSIONS: Decreased food intake in BO was associated with the degree of obstruction and with increased cholecystokinin plasma levels. Biliary drainage improved biochemical and food intake derangements.     

Striking elevation of serum IgA, IgA-containing immune complexes, and IgA rheumatoid factor in clinically silent dermatitis herpetiformis

We describe a patient with dermatitis herpetiformis with immunoglobulin A (IgA)-containing circulating immune complexes and IgA rheumatoid factor who presented with acute renal insufficiency; a renal biopsy specimen showed IgA nephropathy. The renal function and proteinuria spontaneously returned to normal despite markedly elevated levels of IgA-containing circulating immune complexes, IgA rheumatoid factor, and IgA antibodies to some environmental antigens. IgA1 was the predominant subclass. IgA2-containing immune complexes and IgM rheumatoid factor were not detected. Cultures of peripheral blood mononuclear cells produced increased quantities of IgA and IgA rheumatoid factor spontaneously and after pokeweed mitogen stimulation. These data indicate that renal function can improve and remain normal despite the presence of increased levels of IgA-containing circulating immune complexes and IgA rheumatoid factor.     

胆、肠菌群差异性与胆囊胆固醇结石形成关系

目的 基于胆囊胆固醇结石患者胆道菌群、肠道菌群差异性,探讨胆、肠菌群交互与胆囊胆固醇结石形成关系.方法 选择2020年1月至2020年6月由沧州市人民医院诊疗的胆囊胆固醇结石患者42例为研究对象,记入胆固醇结石组;胆囊炎、胆囊息肉诊治等非胆固醇结石患者40例为非胆固醇结石组.采用Illumina测序技术测序并进行细菌O...     

Anaerobes in biliary tract infection

Bile specimens from sixty-nine patients who had undergone biliary tract surgery or PTC have been subjected to bacteriological study by anaerobic and aerobic techniques. Among 50 specimens from the patients with hepatolithiasis, anaerobes were detected in 74.0%, and aerobes in 98.0%. 11 bile specimens from cholecystolithiasis, only 27.3% anaerobes and 36.4% aerobes were detected. Eight patients with biliary duct tumour had sterile bile. The most common isolated anaerobes was bacteroides and with an average of 1.7 species detected. All bile specimens are mixed infections. The incidence of bacterial infection are higher in the pigmented calcium stone than cholesterol stone. This study showed that metronidazole is the drug of choice in the treatment of anaerobic bile infection.     

胆囊与胆管胆汁细菌培养及药敏分析的比较研究

目的探讨胆道感染者胆囊与胆管胆汁中的细菌分布、细菌培养阳性率及菌群对抗生素的敏感性。方法选择2005年6月至2007年10月住院手术的273例胆道感染患者的胆汁标本进行细菌培养及药敏试验分析，对培养结果阳性胆汁的细菌分布及药敏结果进行统计分析。结果273份胆汁标本中149例培养阳性，其中胆囊胆汁17例，培养阳性率为19．8％，胆管胆汁132例，培养阳性率为61．7％。共分离出G^-杆菌127株，G^＋球菌74株，真菌0株。引起胆道感染的病原菌依次为大肠埃希氏菌、肠球菌、铜绿假单胞菌和葡萄球菌。药敏结果显示，G^-杆菌对亚胺培南、美罗培南、头孢吡肟及丁胺卡那霉素耐药率最低，对氨苄西林、哌拉西林、头孢唑啉及复方新诺明高度耐药。G^＋球菌对替考拉宁、万古霉素及氯霉素耐药最低。结论胆道感染仍以G^-杆菌占主要地位，但G^＋球菌感染呈现出明显上升势头。胆管胆汁细菌感染率较胆囊胆汁高，且细菌对临床常用抗生素的耐药性明显增加。     

Differences in biliary lipid excretion after major hepatectomy in obstructive jaundiced rats with preoperative internal,external, or no biliary drainage

Necessity of preoperative biliary drainage for patients with obstructive jaundice is still controversial. We recently reported that liver regeneration after major hepatectomy was better restored in a rat model of obstructive jaundice with preoperative internal biliary drainage than that without biliary drainage or with external biliary drainage. The aim of this study was to investigate the differences in biliary lipid excretion after hepatectomy in obstructive jaundiced rats with or without preoperative internal or external biliary drainage. After bile duct ligation for 7 days, rats were randomly divided into the three groups; obstructive jaundice-hepatectomy (OJ-Hx), internal biliary drainage-hepatectomy (ID-Hx), and external biliary drainage-hepatectomy (ED-Hx) groups. 70% hepatectomy and internal biliary drainage were carried out 7 days after biliary decompression in the latter two groups and without biliary decompression in the OJ-Hx group. On the day of and on days 1, 2, 3 and 7 after hepatectomy, the liver weight, DNA synthesis rate, biliary lipids excretion rates, and bile acid composition were determined. In the ID-Hx group, the DNA synthesis rate and relative liver weight were significantly higher than those of the OJ-Hx and ED-Hx groups. The excretion rates of biliary lipids were disturbed in the ED-Hx group compared with those in the ID-Hx group and the values in the OJ-Hx group were in-between the ID-Hx and ED-Hx group. The liver regeneration rate was significantly correlated with bile flow and excretion rates of biliary lipids. The maintenance of enterohepatic circulation of biliary lipids before hepatectomy may be important for the liver regeneration.