Effects of obstructive jaundice on neutrophil production and acquisition of chemotactic activity in the bone marrow

Background and Aims:  Increased numbers and enhanced functions of peripheral neutrophils have been observed in obstructive jaundice. However, the effects of obstructive jaundice on the bone marrow, that is neutrophil production and acquisition of neutrophil chemotactic activity, have been poorly understood. In the present study, differentials of bone marrow cells and chemotactic activity of bone marrow neutrophils were evaluated in bile duct-obstructed rats.
Methods:  Male Wistar rats underwent either bile duct obstruction for 10 days or bile duct obstruction for 4 days followed by 6 days' internal biliary drainage. Differentials of peripheral blood and bone marrow cells were sequentially determined. Chemotactic activity of peripheral and bone marrow neutrophils was evaluated with a modified Boyden method using interleukin-8 (recombinant rat Gro-β) as a chemoattractant.
Results:  Numbers of peripheral neutrophils significantly increased after bile duct obstruction. Significant increases in the myeloid/erythroid (M/E) ratio of bone marrow cells were observed after bile duct obstruction. The neutrophil proliferative pool (promyelocytes and myelocytes) increased initially, followed by an increased neutrophil storage pool (metamyelocytes, bands, and segmented neutrophils). The M/E ratio as well as the neutrophil proliferative and storage pools normalized after internal biliary drainage. Chemotactic activity was enhanced in both peripheral and bone marrow neutrophils after bile duct obstruction, and enhanced chemotaxis was alleviated with internal biliary drainage.
Conclusion:  The present results strongly suggest the principal role of the bone marrow in increasing the number of neutrophils and their chemotactic activity during obstructive jaundice.     

Effects of obstructive jaundice on neutrophil production and acquisition of chemotactic activity in the bone marrow

BACKGROUND AND AIMS: Increased numbers and enhanced functions of peripheral neutrophils have been observed in obstructive jaundice. However, the effects of obstructive jaundice on the bone marrow, that is neutrophil production and acquisition of neutrophil chemotactic activity, have been poorly understood. In the present study, differentials of bone marrow cells and chemotactic activity of bone marrow neutrophils were evaluated in bile duct-obstructed rats. METHODS: Male Wistar rats underwent either bile duct obstruction for 10 days or bile duct obstruction for 4 days followed by 6 days' internal biliary drainage. Differentials of peripheral blood and bone marrow cells were sequentially determined. Chemotactic activity of peripheral and bone marrow neutrophils was evaluated with a modified Boyden method using interleukin-8 (recombinant rat Gro-beta) as a chemoattractant. RESULTS: Numbers of peripheral neutrophils significantly increased after bile duct obstruction. Significant increases in the myeloid/erythroid (M/E) ratio of bone marrow cells were observed after bile duct obstruction. The neutrophil proliferative pool (promyelocytes and myelocytes) increased initially, followed by an increased neutrophil storage pool (metamyelocytes, bands, and segmented neutrophils). The M/E ratio as well as the neutrophil proliferative and storage pools normalized after internal biliary drainage. Chemotactic activity was enhanced in both peripheral and bone marrow neutrophils after bile duct obstruction, and enhanced chemotaxis was alleviated with internal biliary drainage. CONCLUSION: The present results strongly suggest the principal role of the bone marrow in increasing the number of neutrophils and their chemotactic activity during obstructive jaundice.     

Effect of biliary obstruction and internal biliary drainage on hepatic cytochrome P450 isozymes in rats

AIM： To investigate the total cytochrome P450 （CYP） content, microsomal mixed-function oxidase （MFO） activity, and expression of mRNAs for various CYP isozymes in a simple rat model of reversible obstructive jaundice. METHODS： Obstructive jaundice was created in male rats by causing bile duct obstruction with polyester tape. In another group of rats, bile duct obstruction was followed by internal biliary drainage after releasing the tape. The expression of various CYP isozyme mRNAs was semi-quantitatively assessed by competitive RT- PCR. RESULTS： The total CYP content and microsomal MFO activity showed a significant decrease after biliary obstruction, but returned to respective control levels after biliary drainage. A marked reduction in the expression of CYP1A2, 2B1/2, 2C11, 2E1, 3A1, and 3A2 mRNA was detected during biliary obstruction, while expression increased significantly toward the control level after biliary drainage. Although expression of CYP4A1 mRNA showed no reduction during biliary obstruction, it still increased significantly after biliary drainage. CONCLUSION： These results suggest that not only obstructive jaundice, but also the subsequent internal biliary drainage may affect regulatory medications of the synthesis of individual CYP isozymes differently.     

Human neutrophil functions in obstructive jaundice

BACKGROUND/AIMS: The effect of obstructive jaundice on neutrophil function has not been extensively studied. Therefore, the present study aimed at evaluating the effect of obstructive jaundice on human neutrophils. METHODOLOGY: Twelve patients with obstructive jaundice due to common bile duct obstruction underwent endoscopic biliary drainage. Neutrophil functions (chemotaxis and superoxide anion generation) were evaluated before and 7 days after drainage. RESULTS: Neutrophil chemotaxis in response to FMLP (formyl-methionyl-leucyl-phenylalanine) or interleukin-8 was abnormally increased before drainage, and was normalized after drainage. Similarly, enhanced superoxide anion generation in response to FMLP or phorbol myristate acetate before drainage was alleviated after drainage. CONCLUSIONS: The results suggest neutrophil overactivity in patients with obstructive jaundice. The ameliorating effect of biliary drainage on neutrophil overactivity might play a role in the prevention of postoperative complications.     

Primary Gastrointestinal Lymphoma Complicated by Common Bile Duct Obstruction: Report of Two Cases

This report describes two cases, a case of primary small intestinal lymphoma and a case of gastroduodenal lymphoma both producing obstructive jaundice due to invasion of the common bile duct. Oesophagogastroduodenoscopy revealed the lesions and the endoscopic biopsies confirmed the diagnosis of lymphoma in both the cases. Ultrasound examination of the biliary system, followed by percutaneous transhepatic cholangiography, delineated the dilated biliary tree with distal obstruction of the common bile ducts. While radiotherapy alone was sufficient in the case of primary small intestinal lymphoma; drainage procedures were required in the case of gastroduodenal lymphoma to relieve the obstruction of the common bile duct.     

A rare case report of obstructive jaundice caused by mucus-producing cholangiocarcinoma

Rationale:Cholangiocarcinoma is a common cause of obstructive jaundice but is mainly associated with solid mass and not semisolid secretion. In this report, the patient was admitted to the hospital with obstructive jaundice; however, no solid mass was found to lead to jaundice.Patient concerns:The patient developed symptoms of obstructive jaundice for 10 days, including fatigue and yellow skin staining.Diagnoses:Postoperative pathological examination of the bile duct wall revealed cholangioadenocarcinoma, and the jelly like contents were inflammatory secretions.Interventions:The patient underwent laparotomy and was diagnosed with obstructive jaundice. An exploratory laparotomy revealed that the content in the biliary duct tree was a jelly like inflammatory secretion.Outcomes:Follow-up data revealed that the levels of total bilirubin and aminotransferase were normal, and a computed tomography scan showed no tumor mass.Lessons:There are very few reports about obstructive jaundice caused by inflammatory secretion that almost filled up the biliary tree. Internal drainage of the cholestatic bile can be achieved through endoscopic retrograde cholangiopancreatograpy, or external drainage can be achieved through percutaneous transhepatic biliary drainage, which can relieve the symptoms of biliary obstruction and improve the patient''s quality of life.     

胆汁内外引流术对梗阻性黄疸大鼠肺肿瘤坏死因子α、中性粒细胞弹性蛋白酶的影响

目的研究胆汁内外引流方法对梗阻性黄疸大鼠肺肿瘤坏死因子α(TNF-α)、中性粒细胞弹性蛋白酶(NE)水平的影响。方法将64只成年SD雄性大鼠随机分为4组,分别建立梗阻性黄疸(OJ)、胆汁内引流术(ID)、胆汁外引流术(ED)及假手术(SH)4组模型。于2次术后第14天留取肺组织匀浆液标本。采用双抗体夹心酶联免疫吸附法(ELISA)检测10%肺匀浆液TNF-α水平,生化法检测10%肺匀浆液NE水平。结果成功建立了大鼠梗阻性黄疸及内外引流术模型。梗阻性黄疸时大鼠肺TNF-α、NE水平较假手术对照组明显升高(100.893 pg/mL±21.271 pg/mL vs 64.091 pg/mL±13.034 pg/mL,P<0.01;50.396μg/mL±17.388μg/mL vs 39.718μg/mL±9.625μg/mL,P<0.05)。通过胆汁内引流术解除黄疸后,大鼠肺TNF-α浓度(75.141 pg/mL±15.849 pg/mL)与梗阻性黄疸组相比下降明显(P<0.01);而通过胆汁外引流术解除黄疸后,大鼠肺TNF-α浓度仍较高(112.129 pg/mL±36.886 pg/mL),与梗阻性黄疸组相比无差异(P>0.05)。行胆汁内、外引流术后,大鼠肺NE水平均降低(39.390μg/mL±12.410μg/mL、44.790μg/mL±16.681μg/mL),但与梗阻性黄疸组相比内引流明显(P<0.05)、外引流无差异(P>0.05),且内引流恢复至正常水平,与假手术对照组相比无差异(P>0.05)。结论梗阻性黄疸可导致肺组织炎症细胞因子升高,胆汁内引流术可明显改善梗阻性黄疸时肺组织炎症细胞因子水平、甚至接近正常,而胆汁外引流术没有改善肺炎症细胞因子水平,提示术前利用胆汁内引流术解除梗阻性黄疸缓解肺部炎症反应优于外引流术。     

Influence of biliary obstruction on neutrophil chemotaxis

The effect of obstructive jaundice on neutrophil chemotactic function was investigated, with a potent chemotactic factor, IL-8 (recombinant rat GRO-β), in rats that received 7-day bile duct ligation. Carrageenin or IL-8 was injected into a preformed air pouch, and exudate was collected 4 h later for measurement of myeloperoxidase activity. In vitro chemotaxis of peripheral neutrophils to IL-8 was evaluated by a modified Boyden chamber method. Both carrageenin and IL-8 induced significantly pronounced intra-air pouch neutrophil recruitment in the bile duct-ligated group compared with a sham-ligated group. In vitro neutrophil chemotaxis was significantly increased in the bile duct-ligated group compared with the sham-ligated group. The present experimental model suggests enhanced neutrophil chemotaxis to IL-8 in obstructive jaundice. (Received Sept. 10, 1997; accepted Jan. 23, 1998)     

Increased neutrophil chemotaxis in obstructive jaundice: An in vitro experiment in rats

BACKGROUND AND AIMS: Changes in neutrophil functions in obstructive jaundice have been poorly understood. An in vitro experimental study was performed to evaluate the effect of obstructive jaundice on the functions of macrophages (secretion of neutrophil chemoattractants) and neutrophils (chemotaxis and superoxide anion generation). METHODS: Obstructive jaundice was produced in rats by 7 day bile duct ligation. Peripheral neutrophils and peritoneal macrophages were harvested from either normal, sham-ligated or bile duct-ligated rats and supernatants of the monolayers of the respective macrophages were prepared after stimulation with lipopolysaccharide. Neutrophil chemotaxis was evaluated with a modified Boyden method. RESULTS: The supernatant of the bile duct-ligated rat macrophages showed a chemotactic effect on normal rat neutrophils with insignificant difference from the supernatant of the sham-ligated rat macrophages. Chemotaxis of the bile duct-ligated rat neutrophils towards the supernatant of the normal rat macrophages was significantly increased, compared with that of sham-ligated rat neutrophils. Similarly, neutrophils from bile duct-ligated rats showed significantly greater chemotaxis to formyl-methionyl-leucyl-phenylalanine than the sham-ligated rat neutrophils. Superoxide anion generation in response to formyl-methionyl-leucyl-phenylalanine or phorbol myristate acetate was significantly increased in the bile duct-ligated rats compared with the sham-ligated rats. CONCLUSIONS: The results suggest that the neutrophil is primed in terms of chemotaxis and superoxide anion generation in obstructive jaundice. How these activated neutrophils play a role in the inflammatory response to obstructive jaundice should be evaluated.     

Is preoperative biliary drainage necessary according to evidence‐based medicine?

Preoperative biliary drainage has been in use for a long time and is still being performed today in some institutions, but there has been a long-standing issue as to whether the necessity of this procedure has been proven medically. Many problems existed previously, such as systemic complications due to the difficulty in diagnosing and differentiating obstructive jaundice from jaundice left untreated for a long time, or surgeon-based problems such as a lack of surgical skill or undeveloped surgical techniques, or even inexperience in perioperative patient management. These problems, however, are being overcome with time, and the advantages of preoperative biliary drainage are now being questioned according to evidence-based medicine. Several recent controlled trials have clearly shown that preoperative biliary drainage is not necessary for lower bile duct obstruction, although it was noted that surgery after reduction of jaundice by percutaneous transhepatic cholangial drainage (PTCD) was very easily performed. It is important to understand that preoperative biliary drainage is unnecessary for lower bile duct obstruction, whether the technique follows a percutaneous approach, an endoscopic apporach, or stenting. Although it is still being debated, there have already been several reports regarding whether preoperative biliary drainage is necessary for upper bile duct obstruction, such as hilar bile duct carcinoma. This also needs to be clarified by randomized controlled trials. Aside from preoperative biliary drainage, the utilization of biliary drainage or stenting has been fully recognized as important for removing intrahepatic stones or choledochal stones, as well as for emergency drainage for acute cholangitis and for the treatment of unresectable malignant biliary stenosis. Additionally, percutaneous transhepatic cholangioscopy (PTCS), using the PTCD, or percutaneous transhepatic biliary drainage (PTBD) route, plays a major role not only in the removal of biliary stones but also in the diagnosis of cases in which it is difficult to differentiate between benign and malignant lesions.     

A case of percutaneous and transpapillary placements of expandable metallic stents in a patient with cholangiocarcinoma at the hilum of the liver

A 76-year-old woman was admitted with obstructive jaundice. US and MR cholangiopancreatography (MRCP) revealed an inoperative cholangiocarcinoma, 3 cm in diameter at the hilum of the liver, the obstruction of the hepatic duct bifurcation and the separation of bilateral hepatic bile ducts. Percutaneous transhepatic biliary drainage (PTBD) was performed from bilateral hepatic bile ducts. The right PTBD tube was spontaneously extubated. We could not succeed in performing internal biliary drainage across the hilar malignant stricture from a left hepatic bile duct, because of bad angulation. Transpapillary insertion into the common bile duct (CBD) was extremely difficult due to the collapse of the CBD. Endoscopic sphincterotomy (EST) after precutting method was performed. Although we performed the ballooned dilatation of malignant stricture and the insertion of a self-expandable metallic stent (EMS) into a right hepatic bile duct transpapillary. After dilatation of the hilar malignant stricture by the initial EMS, we inserted a guidewire into the CBD through the wire mesh of a stent from the left PTBD tube. We could insert the second EMS from a left hepatic bile duct to the CBD transhepatically, using a dilator and a dilating balloon. Finally, we performed the ballooned dilatation from bilateral hepatic bile ducts to the CBD transpapillary. She was discharged after bilateral internal biliary drainages, successfully.     

Bile duct ligation in rats induces biliary expression of cytokine-induced neutrophil chemoattractant

BACKGROUND & AIMS: Bile duct obstruction causes neutrophilic inflammation of the liver and leads to hepatic fibrosis. In obstructive liver disease, the localization of neutrophils in portal tracts suggests that cells within this region produce neutrophil chemoattractants. In this study, we investigated whether bile duct obstruction in rats induces portal expression of cytokine-induced neutrophil chemoattractant (CINC). METHODS: Rats underwent bile duct ligation for 3 hours to 8 days. CINC regulation was examined in vivo at various intervals by immunohistochemistry, ribonuclease protection, and in situ hybridization. CINC production was also investigated in cell culture, in response to putative stimuli from obstructed liver. RESULTS: Bile duct ligation caused neutrophilic infiltration of the liver within 3 hours. CINC was also rapidly induced, with specific expression identified in biliary cells. Rat intrahepatic biliary cells produced CINC constitutively in culture; when exposed to cholestatic bile, they showed a 12-fold increase in CINC secretion. The effect of bile was not attributable to toxicity or to dissolved cytokines or endotoxin. Mechanical strain, designed to mimic the stretching of biliary cells during obstruction, did not induce CINC. CONCLUSIONS: Biliary cells contribute to hepatic inflammation during cholestasis by producing neutrophil chemoattractants. A major stimulus to biliary chemoattractant production in vivo may be bile itself.     

Portal biliopathy

In patients with portal hypertension, particularly with extrahepatic portal vein obstruction, portal biliopathy producing biliary ductal and gallbladder wall abnormalities are common. Portal cavernoma formation, choledochal varices and ischemic injury of the bile duct have been implicated as causes of these morphological alterations. While a majority of the patients are asymptomatic, some present with a raised alkaline phosphatase level, abdominal pain, fever and cholangitis. Choledocholithiasis may develop as a complication and manifest as obstructive jaundice with or without cholangitis. Endoscopic sphincterotomy and stone extraction can effectively treat cholangitis when jaundice is associated with common bile duct stone(s). Definitive decompressive shunt surgery is sometimes required when biliary obstruction is recurrent and progressive.     

Biliary Tract Obstruction Secondary to Malignant Lymphoma: Experience at a Referral Center

Lymphoma is a rare cause of biliary obstruction and, on cholangiography, may mimic other causes of obstructive jaundice. The optimum treatment for these patients is unclear. The aim of this study is to evaluate the incidence, clinical and imaging findings, management, and outcome of biliary obstruction caused by lymphoma. Our database was searched retrospectively for patients with biliary obstruction due to lymphoma between 1999 and 2005. Biliary obstruction secondary to lymphoma was found in 7 (0.6%) of 1123 patients with malignant biliary obstruction. One patient had benign biliary obstruction related to lymphoma. Of the eight patients (five male, three female; mean age, 34.50 ± 17.93 years), four had Hodgkin’s disease and four had non-Hodgkin’s lymphoma. Biliary obstruction occurred as part of the initial or early presentation of lymphoma in two patients. The most common cause of obstruction was compression of the biliary tract by enlarged lymph nodes (six patients). Cholangiographic appearances were diverse: narrowing of the common bile duct (six patients), splayed and narrowed common bile duct (one patient), and multiple strictures and dilatations of the intrahepatic bile ducts (one patient). Biliary drainage was performed in all patients including endoscopic stent placement in six patients, nasobiliary drainage in one, and choledochoduodenostomy in one. Hyperbilirubinemia resolved in all but one of the patients with a stent; however, none could be maintained in a stent-free condition. Five patients died within 1 year after onset of jaundice. One of the surviving patients developed a late benign stricture at the site of the earlier lymphoma. We conclude that lymphoma should be considered in the differential diagnosis of obstructive jaundice, particularly in younger patients. We suggest that biliary drainage by the endoscopic or percutaneous route is necessary for the treatment of these patients. Late benign strictures may develop. Biliary obstruction is a sign of poor prognosis in lymphoma.     

Extrahepatic Obstructive Jaundice Due to Colorectal Cancer

A prospective registry of patients with obstructive jaundice referred for percutaneous bile duct drainage found six patients with extrahepatic obstruction due to colorectal cancer in a 21-month period. This cause of jaundice in patients with colorectal cancer is not uncommon, and deserves routine diagnostic consideration, even in the presence of intrahepatic metastases. Percutaneous biliary drainage was beneficial for four of the six patients.     

肝门区转移癌所致梗阻性黄疸的内镜支架引流治疗临床效果分析

目的探讨内镜治疗肝门区转移癌所致梗阻性黄疸的临床应用价值。方法2006年开始随机选择自愿应用内镜治疗的晚期肝门区转移癌所致梗阻性黄疸患者,应用内镜胆道塑料内支架技术解除胆道梗阻,观察操作成功率、生存期等评价指标。共治疗肝门转移癌梗阻性黄疸患者38例,其中肝癌13例,胆囊癌3例,胃癌14例,食管癌2例,回肠腺癌1例,胰腺癌5例。结果所有患者治疗成功且临床黄疸完全消退,随访生存期92～521d,平均（185．42±104．41）d。随访观察5例患者更换胆道支架,更换时间3～14个月,平均（8．6±4．1）个月,其中支架移位1例,胆泥阻塞2例,肿瘤阻塞2例。结论内镜支架引流术是肝门区转移癌所致梗阻性黄疸的一种有效治疗方法,具有较高的治疗成功率,可以一定程度延长患者的生存期。     

Biliary decompression promotes Kupffer cell recovery in obstructive jaundice.

BACKGROUND: Jaundiced patients undergoing surgical procedures have an increased risk of Gram negative sepsis with potential morbidity and mortality. Depressed Kupffer cell clearance capacity (KCCC) predisposes jaundiced patients to endotoxaemia and its sequelae. Biliary decompression remains the main therapeutic strategy in obstructive jaundice. AIMS: This study investigates the efficacy of internal (ID) and external biliary drainage (ED) on KCCC in an experimental model of extrahepatic biliary obstruction. METHODS: Adult male Wistar rats (250-300 g) were assigned to one of six groups: sham operated, where the bile duct was mobilised but not divided; bile duct ligation (BDL) for three weeks, and sham operated or BDL for three weeks followed by a second laparotomy and further 21 days of ID or ED, by way of choledochoduodenostomy or choledochovesical fistula respectively. KCCC was measured using an isolated hepatic perfusion technique with FITC labelled latex particles (0.75 mu) as the test probe. Plasma was assayed for bilirubin, endotoxin, and anticore glycolipid antibody (ACGA) concentrations. RESULTS: Jaundiced rats had reduced KCCC (p < 0.001), increased concentrations of ACGA (p < 0.001), and endotoxin (p < 0.001) compared with controls. Biliary drainage for three weeks produced a recovery in KCCC and normalisation of endotoxin and ACGA concentrations, however, external drainage was less effective than ID (p < 0.01). CONCLUSIONS: These data support the hypothesis that endotoxaemia and its mediated effects are integral in the pathophysiology of jaundice. Furthermore, a short period of internal biliary drainage is a useful therapeutic strategy in restoring Kupffer cell function and negating systemic endotoxaemia and consequent complications in biliary obstruction.     

Endoscopic ultrasound-guided choledochoduodenostomy for relieving malignant distal biliary obstruction

Ultrasound-guided biliary drainage is a new and effective method for relieving obstructive lesions of the biliary tract. In the hands of experienced operators, ultrasound-guided diversion of the mid portion of the common bile duct and the duodenal bulb is a feasible strategy for the relief of jaundice secondary to distal obstruction (distal bile duct tumors, pancreatic head cancer, or major duodenal papillary tumor), with low morbidity and mortality rates. The technical aspects of the procedure and its indications are reviewed herein, emphasizing its performance in institutions equipped with experienced personnel adhering to strict study protocols.     

ERCP在不明原因肝外阻塞性黄疸的临床应用

目的探讨内镜逆行胰胆管造影（ERCP）在经常规检查不明原因肝外阻塞性黄疸的临床应用价值。方法收集经B超、cT和,或MRCP检查诊断不明原因胆胰疾病或肝外胆管梗阻病人45例,男28例,女17例,年龄21—80岁,均行ERCP术。结果45例病人行ERCP术,其中42例诊断为胆道微结石（Biliary microlithiasis,BML）,42例均行乳头扩张术／EST4-胆道取石术;3例为胆总管下端炎性狭窄而行胆道内支架植入术;1例ERCP取石术后并发轻症胰腺炎,经内科保守治疗后痊愈,l例因腹痛再发行胆囊切除术,其余患者经ERCP治疗后腹痛、黄疸均缓解。结论BML是不明原因肝外阻塞性黄疸的主要原因,ERCP是不明原因肝外阻塞性黄疸安全、有效的诊断及治疗手段。     

ENDOSCOPIC ULTRASOUND‐GUIDED CHOLEDOCHODUODENOSTOMY

Endoscopic biliary drainage (EBD) may be unsuccessful in some patients, because of failed biliary cannulation or tumor infiltration, limiting endoscopic access to major papilla. The alternative method of percutaneous transhepatic biliary drainage carries a risk of complications, such as bleeding, portal vein thrombus, portal vein occlusion and intra‐ or extra‐abdominal bile leakage. Recently, endoscopic ultrasonography (EUS)‐guided biliary stent placement has been described in patients with malignant biliary obstruction. Technically, EUS‐guided biliary drainage is possible via transgastric or transduodenal routes or through the small intestine using a direct access or rendezvous technique. We describe herein a technique for direct stent insertion from the duodenal bulb for the management of patients with jaundice caused by malignant obstruction of the lower extrahepatic bile duct. We think transduodenal direct access is the best treatment in patients with jaundice caused by inoperable malignant obstruction of the lower extrahepatic bile duct when EBD fails.