Current status of preoperative drainage for distal biliary obstruction

Preoperative biliary drainage (PBD) was developed to improve obstructive jaundice, which affects a number of organs and physiological mechanisms in patients waiting for surgery. However, its role in patients who will undergo pancreaticoduodenectomy for biliary obstruction remains controversial. This article aims to review the current status of the use of preoperative drainage for distal biliary obstruction. Relevant articles published from 1980 to 2015 were identified by searching MEDLINE and PubMed using the keywords “PBD”, “pancreaticoduodenectomy”, and “obstructive jaundice”. Additional papers were identified by a manual search of the references from key articles. Current studies have demonstrated that PBD should not be routinely performed because of the postoperative complications. PBD should only be considered in carefully selected patients, particularly in cases where surgery had to be delayed. PBD may be needed in patients with severe jaundice, concomitant cholangitis, or severe malnutrition. The optimal method of biliary drainage has yet to be confirmed. PBD should be performed by endoscopic routes rather than by percutaneous routes to avoid metastatic tumor seeding. Endoscopic stenting or nasobiliary drainage can be selected. Although more expensive, the use of metallic stents remains a viable option to achieve effective drainage without cholangitis and reintervention.     

Preoperative biliary drainage for malignant biliary obstruction: results from a national database

Background

The impact of preoperative biliary drainage (PBD) on postoperative morbidity and mortality in patients with malignant biliary obstruction is still unclear. We examined short‐term surgical outcomes among drained and non‐drained patients.

Methods

Patients who underwent surgical resection for their malignancies with biliary obstruction were identified using the American College of Surgeons National Surgical Quality Improvement Program Participant Use Files from 2014 to 2015. Mortality and morbidity were compared among patients who had PBD to those who did not undergo biliary drainage prior to surgery.

Results

A total of 2,306 patients were included; of these 1,803 (77.8%) had PBD. The postoperative mortality was 3.0% and 2.2% among direct surgery (DS) group and PBD group, respectively (P = 0.3). Postoperative complications were higher in the PBD group compared to the DS group (27.1% vs. 19.5%; P = 0.0005). Patients in the PBD group had higher risk of sepsis (13.5% vs. 7.2%; P = 0.0001), wound infections (16.5% vs. 10.9%; P = 0.002) and pancreatic fistula (17.5% vs. 12.4%; P = 0.006) compared to the DS group.

Conclusion

Preoperative biliary drainage is associated with increased risk of sepsis and wound infections, but does not impact the postoperative mortality of patients undergoing PBD.     

Endoscopic ultrasound-guided biliary drainage with placement of a fully covered metal stent for malignant biliary obstruction

AIM: To determine the utility of endoscopic ultrasound-guided biliary drainage (EUS-BD) with a fully covered self-expandable metal stent for managing malignant biliary stricture.METHODS: We collected data from 13 patients who presented with malignant biliary obstruction and underwent EUS-BD with a nitinol fully covered self-expandable metal stent when endoscopic retrograde cholangiopancreatography (ERCP) fails. EUS-guided choledochoduodenostomy (EUS-CD) and EUS-guided hepaticogastrostomy (EUS-HG) was performed in 9 patients and 4 patients, respectively.RESULTS: The technical and functional success rate was 92.3% (12/13) and 91.7% (11/12), respectively. Using an intrahepatic approach (EUS-HG, n = 4), there was mild peritonitis (n = 1) and migration of the metal stent to the stomach (n = 1). With an extrahepatic approach (EUS-CD, n = 10), there was pneumoperitoneum (n = 2), migration (n = 2), and mild peritonitis (n = 1). All patients were managed conservatively with antibiotics. During follow-up (range, 1-12 mo), there was re-intervention (4/13 cases, 30.7%) necessitated by stent migration (n = 2) and stent occlusion (n = 2).CONCLUSION: EUS-BD with a nitinol fully covered self-expandable metal stent may be a feasible and effective treatment option in patients with malignant biliary obstruction when ERCP fails.     

经皮肝穿刺胆道内支架植入治疗恶性胆道梗阻64例

目的：总结经皮肝穿刺胆道内支架植入治疗恶性梗阻性黄疸的经验，探讨其临床疗效及价值。方法：64例患者均采用X线透视下经皮肝穿刺胆道内支架植入术治疗恶性梗阻性黄疽。根据梗阻部位的不同解剖决定放置支架的方式。结果：64例患者中，50例植入单支支架于肝总管或(和)胆总管，14例植入2支以上支架于总管和分支胆管，其中2例肝内胆管支架的桥接通过肝实质。58例患者2周内血清胆红素降低75％以上。结论：经皮肝穿刺刺内支架植入是治疗恶性胆道梗阻性的有效方法。     

选择性胆管外引流对梗阻性黄疸大鼠肝切除术后肝再生的影响

90%以上肝门部胆管癌合并有不同程度的梗阻性黄疸,且多为完全梗阻性.术前多采取经皮经肝胆管引流(PTBD)以降低胆红素水平.肝门胆管癌PTBD与其他引起梗阻性黄疸的疾病有所不同:技术上困难,需多支肝管引流;引流的肝叶有可能是切除的肝叶;导管并发症发病率高等.     

术前胆道引流对低位恶性胆道梗阻患者行胰十二指肠切除术后的影响

目的 评价术前胆道引流(PBD)对低位恶性胆道梗阻性黄接受胰十二指肠切除术(PD)后的并发症、死亡率及住院时间的影响.方法 回顾性总结分析2001年1月至2010年12月期间接受PD术的71例低位恶性胆道梗阻患者的临床资料.术前胆道引流方法包括经皮肝穿刺胆道引流(PTCD)、逆行胰胆管造影术(ERCP)及胆囊造瘘术,71例中行PBD患者19例(26.8%),未行PBD患者52例(73.2%).结果 PBD组总胆红素(TBIL)在引流前为(424.9±129.9)μmol/L,引流后下降为(77.7±48.6)μmol/L,差异具有统计学意义(t=11.1,P＜0.001).PBD组直接胆红素(DBIL)在引流前为(300.7±98.1)μmol/L,引流后下降为(60.0±34.5)μmol/L,差异具有统计学意义(t=10.7,P＜0.001).PBD组谷丙转氨酶(ALT)在引流前为(227.9±275.8)U/L,引流后下降为(90.3±66.5)U/L,差异具有统计学意义(t=2.5,P=0.023).PBD组术中输血量为(589±93)ml,非PBD组为(603±71)ml,差异无统计学意义(t=-110,P=0.913).PBD组术后并发症发生率为52.6%(10/19),非PBD组为55.8%(29/52),差异无统计学意义(P＞0.05).PBD组术后住院时间为(33±3)d,非PBD组为(25±2)d,差异无统计学意义(P＞0.05).结论 对黄疸较重、肝功能严重受损的患者,行PBD可有效改善患者的一般状况,但并未降低PD术后并发症发生率及死亡率,也未减少术后的住院时间.     

Endoscopic ultrasound‐guided biliary drainage of hilar biliary obstruction

Only 20–30% of patients with hilar cholangiocarcinoma (CC) are candidates for potentially curative resection. However, even after curative (R0) resection, these patients have a disease recurrence rate of up to 76%. The prognosis of hilar cholangiocarcinoma (CC) is limited by tumor spread along the biliary tree leading to obstructive jaundice, cholangitis, and liver failure. Therefore, palliative biliary drainage may be a major goal for patients with hilar CC. Endoscopic retrograde cholangiopancreatography (ERCP) with stent placement is an established method for palliation of patients with malignant biliary obstruction. However, there are patients for whom endoscopic stent placement is not possible because of failed biliary cannulation or tumor infiltration that limits transpapillary access. In this situation, percutaneous transhepatic biliary drainage (PTBD) is an alternative method. However, PTBD has a relatively high rate of complications and is frequently associated with patient discomfort related to external drainage. Endoscopic ultrasound‐guided biliary drainage has therefore been introduced as an alternative to PTBD in cases of biliary obstruction when ERCP is unsuccessful. In this review, the indications, technical tips, outcomes, and the future role of EUS‐guided intrahepatic biliary drainage, such as hepaticogastrostomy or hepaticoduodenostomy, for hilar biliary obstruction will be summarized.     

胆汁内外引流术对梗阻性黄疸大鼠肝脏Kupffer细胞CD14表达的影响

目的探讨胆汁内外引流术对梗阻性黄疸大鼠肝脏Kupffer细胞CD14表达的影响。方法将60只成年SD雄性大鼠随机分为4组,梗阻性黄疸组(OJ组)、胆汁内引流术组(ID组)、胆汁外引流术组(ED组)及假手术组(SH组)并分别建立模型;采用免疫组织化学染色及半定量分析的方法测定各组大鼠肝脏Kupffer细胞CD14的表达情况。结果 OJ组大鼠肝脏Kupffer细胞CD14表达明显强于SH组(P0.01),ID组与OJ组比较表达明显降低(P0.01),ED组与OJ组比较无显著性差异(P=0.5907)。结论梗阻性黄疸时胆汁内引流术在改善Kupffer细胞CD14表达方面优于胆汁外引流术,提示胆汁内引流术优于外引流术的机制可能与肝脏Kupffer细胞CD14表达过程有关。     

Technical tips and troubleshooting of endoscopic biliary drainage for unresectable malignant hilar biliary obstruction

Unresectable malignant hilar biliary obstruction (MHBO) occurs in various diseases, such as cholangiocarcinoma, gallbladder carcinoma, hepatocellular carcinoma, pancreatic cancer, and lymph node metastasis of the hilum of the liver. The majority of patients with advanced MHBO are not candidates for surgical resection because of the tumor location in the hepatic hilum and adjacent areas, advanced tumor stage, or comorbidities. Therefore, these patients often have a poor prognosis in terms of survival and quality of life. Most of these patients will require non‐surgical, palliative biliary drainage. To date, various biliary drainage techniques for unresectable MHBO (UMHBO) have been reported. Of these techniques, endoscopic biliary drainage is currently considered to be the most safe and minimally invasive procedure. However, endoscopic biliary drainage for UMHBO is still not standardized regarding the optimal stent, drainage area, stenting method, and reintervention technique. Recently, towards standardization of this technique for UMHBO, clinical research and trials including randomized controlled trials have been performed. In this article, we reviewed the most important issues regarding endoscopic biliary drainage for UMHBO, focusing on prospective studies. We also described in detail the techniques and future perspectives of endoscopic biliary drainage in patients with UMHBO.     

非酒精性脂肪肝大鼠肝细胞色素P450 1A1基因及表达变化的意义

目的研究非酒精性脂肪肝大鼠肝细胞色素P450 1A1基因和表达变化及其意义.方法雄性Wistar大鼠40只,随机分为两组,正常对照组8只,高脂饮食组2、4、8、12各8只,紫外分光光度计法检测P450 1A1活性(7-乙氧异恶唑0-脱乙基酶,EROD);免疫组织化学和Western blot方法测定肝细胞色素P450 1A1表达变化,逆转录聚合酶链反应测定肝细胞色素P450 1A1 mRNA表达变化.结果脂肪肝2、4、8和12周EROD活性分别为325.07±59.68、345.25±49.28、468.95±55.28和548.68±43.25 nmol·mg-1·min-1,与正常对照组260.42±35.32 nmol·mg-1·min-1比较明显增高(P＜0.01),肝细胞色素P450 1A1基因及蛋白表达随着脂肪肝程度的加重明显增强.结论非酒精性脂肪肝大鼠肝细胞色素P450 1A1基因和表达变化与脂肪肝引起的肝脏损害程度密切相关.     

经内镜放置胆管金属支架联合鼻胆管引流治疗恶性胆管梗阻

目的探讨经内镜放置胆管金属支架联合鼻胆管引流对恶性胆管梗阻的治疗效果。方法 115例失去手术机会的恶性胆管梗阻患者行经内镜逆行胰胆管造影下放置胆管支架,其中48例行胆管塑料支架引流术,30例行胆管金属支架引流术,37例行胆管金属支架联合鼻胆管引流术;分析各组引流效果、成功率、早期并发症和胆管再堵塞发生情况。结果塑料支架组、金属支架组及金属支架联合鼻胆管组的谷丙转氨酶(ALT)、总胆红素(TBIL)、直接胆红素(DBIL)和碱性磷酸酶(AKP)在手术后均有明显降低(P0.05);手术后1周金属支架联合鼻胆管组的TBIL和DBIL明显低于塑料支架组、金属支架组(P0.05),塑料支架组和金属支架组相比,差异无统计学意义(P0.05);术后3个月内金属支架组和金属支架联合鼻胆管组再堵塞的发生率明显低于塑料支架组(P0.05),金属支架组和金属支架联合鼻胆管组相比,差异无统计学意义(P0.05);塑料支架组的手术成功率与金属支架组及金属支架联合鼻胆管组相比,差异无统计学意义(P0.05),塑料支架组的早期并发症发生率明显高于金属支架联合鼻胆管组,差异有统计学意义(P0.05)。结论经内镜逆行胰胆管造影下放置胆管金属支架联合鼻胆管对于恶性胆管梗阻有确切的引流效果。     

Effect of beta-carotene on hepatic cytochrome P-450 in ethanol-fed rats

BACKGROUND: Hepatotoxicity of ethanol is increased by beta-carotene in both rodents and nonhuman primates. Furthermore, in smokers who are also drinkers, beta-carotene increases the incidence of pulmonary cancer. The hepatotoxicity was associated with proliferation of the membranes of the smooth endoplasmic reticulum, suggesting the involvement of cytochromes P-450. Therefore, the aim of the present study was to assess the effect of beta-carotene and ethanol treatment on rodent hepatic cytochromes P-450. METHODS AND RESULTS: Weanling male Sprague-Dawley rats were pair-fed beta-carotene (56.5 mg/l of diet) for 8 weeks, with and without ethanol (Lieber-DeCarli, 1994 liquid diet). As expected, ethanol increased CYP2E1 (measured by Western blots) from 67 +/- 8 to 317 +/- 27 densitometric units (p < 0.001). Furthermore, beta-carotene potentiated the ethanol induction to 442 +/- 38 densitometric units (p < 0.01) with a significant interaction (p = 0.012). The rise was confirmed by a corresponding increase in the hydroxylation of p-nitrophenol, a specific substrate for CYP2E1, and by the inhibition with diethyl dithiocarbamate (50 microM). Beta-carotene alone also significantly induced CYP4A1 protein (328 +/- 49 vs. 158 +/- 17 densitometric units, p < 0.05). The corresponding CYP4A1 mRNA (measured by Northern blots) was also increased (p < 0.05) and there was a significant interaction of the two treatments (p = 0.015). The combination of ethanol and beta-carotene had no significant effect on either total cytochrome P-450 or CYP1A1/2, CYP2B, CYP3A, and CYP4A2/3 contents. CONCLUSIONS: Beta-carotene potentiates the CYP2E1 induction by ethanol in rat liver and also increases CYP4A1, which may, at least in part, explain the associated hepatotoxicity.     

Multiple mechanisms in indomethacin-induced impairment of hepatic cytochrome P450 enzymes in rats

BACKGROUND & AIMS: Indomethacin impairs liver microsomal monooxygenase activities mediated by cytochrome P450 (CYP). We investigated the inhibition mechanism and the isoform selectivity in vitro and in vivo. METHODS: In an in vitro study, liver microsomes from male Wistar rats were preincubated with indomethacin and a reduced nicotinamide adenine dinucleotide phosphate-generating system, followed by assay of monooxygenase activities indicative of several CYP isoforms. In an in vivo study, rats were intraperitoneally treated with indomethacin, followed by preparation of microsomes and the enzyme assays. RESULTS: The preincubation of microsomes with indomethacin and reduced nicotinamide adenine dinucleotide phosphate decreased CYP3A2 activity but not any other isoforms. Kinetic analysis showed the mechanism-based inactivation of CYP3A2. The metabolism of [14C]indomethacin resulted in covalent binding to microsomal protein, which was diminished by inhibiting CYP3A enzyme. Administration of indomethacin caused impairment of not only CYP3A2 but also other CYP isoforms. Rats were protected from the impairment of the CYP enzymes except CYP3A2 by depleting macrophages and inhibiting inducible nitric oxide synthase. CONCLUSIONS: Metabolism of indomethacin causes inactivation of CYP3A2, which is the result of the covalent binding of its metabolite, whereas partially selective in vivo impairment of CYP isoforms is suggested to be indirect inhibition by inflammatory mediators probably released from Kupffer cells.     

Histological changes at an endosonography-guided biliary drainage site： A case report

Endosonography-guided biliary drainage （ESBD） is a new method enabling internal drainage of an obstructed bile duct. However, the histological conditions associated with fistula development via the duodenum to the bile duct have not been reported. We performed ESBD 14 d preoperatively in a patient with an ampullary carcinoma and histologically confirmed changes in and around the fistula. The female patient developed no complications relevant to ESBD. Levels of serum bilirubin and hepatobiliary enzymes declined quickly, and pancreatoduodenectomy was carried out uneventfully. The resected specimen was sliced and stained with hematoxylin-eosin. Histological evaluation of the puncture site in the duodenum and bile-duct wall, and the sinus tract revealed no hematoma, bile leakage, or abscess in or around the sinus tract. Little sign of granulation, fibrosis, and inflammatory cell infiltration was observed. Although further large-scale confirmatory studies are needed, the findings here may encourage more active use of ESBD as a substitute for percutaneous transhepatic drainage in cases with failed/difficult endoscopic biliary stenting.     

Clinical utility of treatment method conversion during single-session endoscopic ultrasound-guided biliary drainage

BACKGROUND Although several techniques for endoscopic ultrasound-guided biliary drainage(EUS-BD)are available at present,an optimal treatment algorithm of EUS-BD has not yet been established.AIM To evaluate the clinical utility of treatment method conversion during single endoscopic sessions for difficult cases in initially planned EUS-BD.METHODS This was a single-center retrospective analysis using a prospectively accumulated database.Patients with biliary obstruction undergoing EUS-BD between May 2008 and April 2016 were included.The primary outcome was to evaluate the improvement in EUS-BD success rates by converting the treatment methods during a single endoscopic session.Secondary outcomes were clarification of the factors leading to the conversion from the initial EUS-BD and the assessment of efficacy and safety of the conversion as judged by technical success,clinical success,and adverse events(AEs).RESULTS A total of 208 patients underwent EUS-BD during the study period.For 18.8%(39/208)of the patients,the treatment methods were converted to another EUSBD technique from the initial plan.Biliary obstruction was caused by pancreatobiliary malignancies,other malignant lesions,biliary stones,and other benign lesions in 22,11,4,and 2 patients,respectively.The reasons for the difficulty with the initial EUS-BD were classified into the following 3 procedures:Target puncture(n=13),guidewire manipulation(n=18),and puncture tract dilation(n=8).Technical success was achieved in 97.4%(38/39)of the cases and clinical success was achieved in 89.5%of patients(34/38).AEs occurred in 10.3%of patients,including bile leakage(n=2),bleeding(n=1),and cholecystitis(n=1).The puncture target and drainage technique were altered in subsequent EUSBD procedures in 25 and 14 patients,respectively.The final technical success rate with 95%CI for all 208 cases was 97.1%(95%CI:93.8%-98.9%),while that of the initially planned EUS-BD was 78.8%(95%CI:72.6%-84.2%).CONCLUSION Among multi-step procedures in EUS-BD,guidewire manipulation appeared to be the most technically challenging.When initially planned EUS-BD is technically difficult,treatment method conversion in a single endoscopic session may result in successful EUS-BD without leading to severe AEs.     

Treatment of malignant biliary obstruction by combined percutaneous transhepatic biliary drainage with local tumor treatment

AIM: To evaluate the utility of local tumor therapy combined with percutaneous transhepatic biliary drainage (PTBD) for malignant obstructive biliary disease. METHODS: A total of 233 patients with malignant biliary obstruction were treated in our hospital with PTBD by placement of metallic stents and/or plastic tubes. After PTBD, 49 patients accepted brachytherapy or extra-radiation therapy or arterial infusion chemotherapy. The patients were followed up with clinical and radiographic evaluation. The survival and stent patency rate were calculated by Kaplan-Meier survival analysis. RESULTS: Twenty-two patients underwent chemotherapy (11 cases of hepatic carcinoma, 7 cases of pancreatic carcinoma, 4 cases of metastatic lymphadenopathy), and 14 patients received radiotherapy (10 cases of cholan-giocarcinoma, 4 cases of pancreatic carcinoma), and 13 patients accepted brachytherapy (7 cases of cholangio-carcinoma, 3 cases of pancreatic carcinoma, 4 cases of metastatic lymphadenopathy). The survival rate of the local tumor treatment group at 1, 3, 6, and 12 months was 97.96%, 95.92%, 89.80%, and 32.59% respectively, longer than that of the non treatment group. The patency rate at 1, 3, 6, and 12 months was 97.96%, 93.86%, 80.93%, and 56.52% respectively. The difference of patency rate was not significant between treatment group and non treatment group. CONCLUSION: Our results suggest that local tumor therapy could prolong the survival time of patients with malignant biliary obstruction, and may improve stent patency.     

细胞色素P450基因多态性对他克莫司临床应用的影响

肝移植是终末期肝病患者最有效的治疗手段,而免疫抑制剂的应用是影响患者移植术后长期存活的关键。本文介绍了最常用的免疫抑制剂——他克莫司的作用机制,以及细胞色素P450基因多态性对他克莫司应用影响的最新研究进展。为临床上合理使用他克莫司,减少相关并发症的发生,提高肝移植患者的长期生存率提供参考。