Efficacy and safety of percutaneous transhepatic biliary radiofrequency ablation in patients with malignant obstructive jaundice

BACKGROUND Percutaneous transhepatic cholangiodrainage(PTCD)and endoscopic retrograde cholangiopancreatography/endoscopic nasobiliary drainage are the most common clinical procedures for jaundice control in patients with unresectable malignant obstructive jaundice,yet the safety and effect of endobiliary radiofrequency ablation(EB-RFA)combined PTCD is rarely reported,in this article,we report our experience of EB-RFA combined PTCD in such patients.AIM To retrospectively study the efficacy and safety of EB-RFA combined PTCD in patients with unresectable malignant obstructive jaundice.METHODS Patients with unresectable malignant obstructive jaundice treated with EB-RFA under PTCD were selected,the bile ducts of the right posterior lobe was selected as the target bile ducts in all cases.The general conditions of all patients,preoperative tumour markers,total bilirubin(TBIL),direct bilirubin(DBIL),albumin(ALB),alkaline phosphatase(ALP),and glutamyl transferase(GGT)before and on the 7th day after the procedure,as well as perioperative complications,stent patency time and patient survival were recorded.RESULTS All patients successfully completed the operation,TBIL and DBIL decreased significantly in all patients at the 7th postoperative day(P=0.009 and 0.006,respectively);the values of ALB,ALP and GGT also decreased compared with the preoperative period,but the difference was not statistically significant.Perioperative biliary bleeding occurred in 2 patients,which was improved after transfusion of blood and other conservative treatments,pancreatitis appeared in 1 patient after the operation,no serious complication and death happened after operation.Except for 3 patients with loss of visits,the stent patency rate of the remaining 14 patients was 100%71%and 29%at the 1^(st),3^(rd),and 6^(th)postoperative months respectively,with a median survival of 4 months.CONCLUSION EB-RFA under PTCD in patients with unresectable malignant obstructive jaundice has a satisfactory therapeutic effect and high safety,which is worthy of further clinical practice.

Endoscopic ultrasound-guided biliary drainage vs percutaneous transhepatic bile duct drainage in the management of malignant obstructive jaundice

BACKGROUND Malignant obstructive jaundice(MOJ)is a condition characterized by varying degrees of bile duct stenosis and obstruction,accompanied by the progressive development of malignant tumors,leading to high morbidity and mortality rates.Currently,the two most commonly employed methods for its management are percutaneous transhepatic bile duct drainage(PTBD)and endoscopic ultrasound-guided biliary drainage(EUS-BD).While both methods have demonstrated favorable outcomes,additional research needs to be performed to determine their relative efficacy.To compare the therapeutic effectiveness of EUS-BD and PTBD in treating MOJ.METHODS This retrospective analysis,conducted between September 2015 and April 2023 at The Third Affiliated Hospital of Soochow University(The First People’s Hospital of Changzhou),involved 68 patients with MOJ.The patients were divided into two groups on the basis of surgical procedure received:EUS-BD subgroup(n=33)and PTBD subgroup(n=35).Variables such as general data,preoperative and postoperative indices,blood routine,liver function indices,myocardial function indices,operative success rate,clinical effectiveness,and complication rate were analyzed and compared between the subgroups.RESULTS In the EUS-BD subgroup,hospital stay duration,bile drainage volume,effective catheter time,and clinical effect-iveness rate were superior to those in the PTBD subgroup,although the differences were not statistically significant(P>0.05).The puncture time for the EUS-BD subgroup was shorter than that for the PTBD subgroup(P<0.05).Postoperative blood routine,liver function index,and myocardial function index in the EUS-BD subgroup were significantly lower than those in the PTBD subgroup(P<0.05).Additionally,the complication rate in the EUS-BD subgroup was lower than in the PTBD subgroup(P<0.05).CONCLUSION EUS-BD may reduce the number of punctures,improve liver and myocardial functions,alleviate traumatic stress,and decrease complication rates in MOJ treatment.

Changes over time in treatment for obstructive jaundice

This editorial discusses an article by Peng et al.This study reviewed the efficacy and safety of a new approach for treating obstructive jaundice.Although the pathophysiology of obstructive jaundice has not yet been fully elucidated,pro-gress has been made in its management.There are two aspects of obstructive jaundice:Cholestatic status and absence of bile in the intestinal lumen.Internal biliary drainage resolved both the conditions.Clinically,endoscopic retrograde biliary drainage(ERBD)has replaced percutaneous transhepatic biliary drainage,and ERBD is transitioning to endoscopic ultrasound guided biliary drainage.This editorial briefly explains the mechanism and treatment of obstructive jaundice and the prospects of this new internal biliary drainage technique.

Pathophysiological consequences and treatment strategy of obstructive jaundice

Obstructive jaundice(OJ)is a common problem in daily clinical practice.However,completely understanding the pathophysiological changes in OJ remains a challenge for planning current and future management.The effects of OJ are widespread,affecting the biliary tree,hepatic cells,liver function,and causing systemic complications.The lack of bile in the intestine,destruction of the intestinal mucosal barrier,and increased absorption of endotoxins can lead to endotoxemia,production of proinflammatory cytokines,and induce systemic inflammatory response syndrome,ultimately leading to multiple organ dysfunction syndrome.Proper management of OJ includes adequate water supply and electrolyte replacement,nutritional support,preventive antibiotics,pain relief,and itching relief.The surgical treatment of OJ depends on the cause,location,and severity of the obstruction.Biliary drainage,surgery,and endoscopic intervention are potential treatment options depending on the patient's condition.In addition to modern medical treatments,Traditional Chinese medicine may offer therapeutic benefits for OJ.A comprehensive search was conducted on PubMed for relevant articles published up to August 1970.This review discusses in detail the pathophysiological changes associated with OJ and presents effective strategies for managing the condition.

Application of endoscopic retrograde cholangiopancreatography for treatment of obstructive jaundice after hepatoblastoma surgery:A case report

BACKGROUND We aimed to investigate the effectiveness of endoscopic retrograde cholangiopan-creatography(ERCP)for treating obstructive jaundice(OJ)post hepatoblastoma(HB)surgery(post-HB OJ)by analyzing the data of a case and performing a literature review.CASE SUMMARY Clinical data of one patient with post-HB OJ treated by ERCP were retrospectively analyzed.Furthermore,clinical characteristics and insights into the diagnosis and treatment of post-HB OJ in children were summarized via searching various databases and platforms,such as China National Knowledge Infrastructure,Wanfang database,CQVIP database,PubMed,Ringer Link,and Google Scholar.The patient reported herein underwent five chemotherapy sessions after the diagnosis of HB and right hemihepatectomy after tumor size reduction;these were followed by two postoperative chemotherapy sessions.Three months postoperatively,the patient developed icteric sclera,strong tea-colored urine,and clay-like stools,and showed signs of skin itchiness;blood analysis showed significantly an increased conjugated bilirubin(CB)level(200.3μmol/L).Following the poor efficacy of anti-jaundice and hepatoprotective treatments,the patient underwent ERCP.Intraoperative imaging showed a dilated bile duct in the porta hepatis with significant distal stenosis.A 5 Fr nasopancreatic tube was placed in the dilated area through the stricture for external drainage,and the patient was extubated on postoperative day 6.Postoperatively,the patient’s stool turned yellow,and the CB level decreased to 78.2μmol/L.Fifteen days later,ERCP was repeated due to unrelieved jaundice symptoms,wherein a 7 Fr naso-biliary drainage tube was successfully placed.Three months post-ERCP,the jaundice symptoms resolved,and the CB level was reduced to 33.2μmol/L.A follow-up examination one year postoperatively revealed no jaundice symptoms and normal CB level.CONCLUSION Post-HB OJ is rare.Compared to biliary tract reconstruction,ERCP is less invasive and has a better therapeutic effect.

Effect of preoperative biliary drainage on malignant obstructive jaundice:A meta-analysis

AIM: To evaluate the effect of preoperative biliary drainage (PBD) on obstructive jaundice resulting from malignant tumors. METHODS: According to the requirements of Cochrane systematic review, studies in the English language were retrieved from MEDLINE and Embase databases from 1995 to 2009 with the key word "preoperative biliary drainage". Two reviewers independently screened the eligible studies, evaluated their academic level and extracted the data from the eligible studies confirmed by cross-checking. Data about patients with and without PBD after resection of malignant tumors were processed for meta-analysis using the Stata 9.2 software, including postoperative mortality, incidence of postoperative pancreatic and bile leakage, abdominal abscess, delayed gastric emptying and incision infection.RESULTS: Fourteen retrospective cohort studies involving 1826 patients with malignant obstructive jaundice accorded with our inclusion criteria, and were included in meta-analysis. Their baseline characteristics were comparable in all the studies. No significant difference was found in combined risk ratio (RR) of postoperative mortality and incidence of pancreatic and bile leakage, abdominal abscess, delayed gastric emptying between patients with and without PBD. However, the combined RR for the incidence of postoperative incision infection was improved better in patients with PBD than in those without PBD (P < 0.05). CONCLUSION: PBD cannot significantly reduce the post-operative mortality and complications of malignant obstructive jaundice, and therefore should not be used as a preoperative routine procedure for malignant obstructive jaundice.

Effect of postoperative early enteral nutrition on clinical outcomes and immune function of cholangiocarcinoma patients with malignant obstructive jaundice

BACKGROUND Most cholangiocarcinoma patients with malignant obstructive jaundice(MOJ)have varying degrees of malnutrition and immunodeficiency preoperatively.Therefore,perioperative nutritional support has important clinical significance in the treatment of cholangiocarcinoma.AIM To investigate the effects of postoperative early enteral nutrition(EEN)on immunity function and clinical outcomes of cholangiocarcinoma patients with MOJ.METHODS This prospective clinical study included 60 cholangiocarcinoma patients with MOJ who underwent surgery.The patients were randomly divided into an experimental group and a control group according to the nutrition support modes.The control group received postoperative total parenteral nutrition(TPN),whereas the experimental group received postoperative EEN and parenteral nutrition(PN;EEN+PN).The clinical outcomes,postoperative immune function,incidences of surgical site infection and bile leakage,intestinal function recovery time,average hospitalization days,and hospitalization expenses of the two groups were assessed on postoperative days(PODs)1,3,and 7.RESULTS The CD3+T,CD4+T,CD8+T,and CD4+T/CD8+T cell count and the immunoglobulin(Ig)G,IgM,and IgA levels in the EEN+PN group were significantly higher than those in the TPN group on PODs 3 and 7(P<0.05),whereas no significant differences in the CD3+T,CD4+T,CD8+T,and CD4+T/CD8+T cell counts and IgG,IgM,and IgA levels before operation and on POD 1 were found between the two groups(P>0.05).The intestinal function recovery time and postoperative hospital stay were shorter(P<0.001 for both)in the EEN+PN group than in the TPN group.The hospitalization expenses of the EEN+PN group were lower than those of the TPN group(P<0.001).However,the incidence of abdominal distension was higher than in the EEN+PN group than in the TPN group(P<0.05).The incidence rates of biliary leakage and surgical site infection were not significantly different between the two groups(P>0.05).CONCLUSION A postoperative EEN program could reduce the incidence of postoperative complications and improve the clinical outcomes and immune functions of cholangiocarcinoma patients with MOJ and is thus beneficial to patient recovery.

Surgical mortality in patients with malignant obstructive jaundice: a multivariate discriminant analysis

OBJECTIVE: To estimate the operative mortality in patients with malignant obstructive jaundice. METHODS: Twelve risk factors were analyzed using multivariate discriminant analysis in 90 patients who had been operated on. RESULTS: Operative mortality was significantly related to the following factors: age, duration of jaundice, packed RBC volume, white blood cell count and concentration of blood urine nitrogen; it was not significantly related to diseases and types of operation. The following formula was obtained: packed RBC volume×0.09954-age×0. 04018-blood urine nitrogen×0. 23693-duration of jaundice× 2. 07388-WBC count×0. 21118+5. 26593. With this formula, an operative mortality of 77. 8% was predicted. CONCLUSION: With a positive value from the formula, the patient should be operated on; otherwise non-operative treatment is advocated.

Percutaneous biliary stent combined with brachytherapy using 125I seeds for treatment of unresectable malignant obstructive jaundice:A meta-analysis

BACKGROUND Malignant obstructive jaundice(MOJ)is a common pathologic manifestation of malignant biliary obstruction.Recently,several clinical trials have explored the clinical effectiveness of intraluminal^(125)I seed-based brachytherapy for MOJ patients,and various outcomes have been reported.AIM To assess the efficacy and safety of percutaneous biliary stents with^(125)I seeds compared to conventional metal stents in patients with unresectable MOJ.METHODS A systematic search of English-language databases(PubMed,Embase,Cochrane Library,and Web of Science)was performed to identify studies published prior to June 2020 that compared stents with or without^(125)I seeds in the treatment of unresectable MOJ.The outcomes analyzed included primary outcomes(stent patency and overall survival)and secondary outcomes(complications and liver function parameters).RESULTS Six randomized controlled trials and four retrospective studies involving 875 patients were eligible for the analysis.Of the 875 included patients,404 were treated with^(125)I seed stents,while 471 were treated with conventional stents.Unadjusted pooled analysis demonstrated that compared to conventional stents,^(125)I seed stents extended the stent patency time[hazard ratio(HR)=0.36,95%confidence interval(CI)=0.28-0.45,P<0.0001]and overall survival period(HR=0.52,95%CI=0.42–0.64,P<0.00001).Subgroup analyses based on the type of^(125)I seed stent and type of study design showed consistent results.However,there were no significant differences in the occurrence of total complications[odds ratio(OR)=1.12,95%CI=0.75-1.67,P=0.57],hemobilia(OR=1.02,95%CI=0.45-2.3,P=0.96),pancreatitis(OR=1.79,95%CI=0.42-7.53,P=0.43),cholangitis(OR=1.13,95%CI=0.60-2.13,P=0.71),or pain(OR=0.67,95%CI=0.22-2,P=0.47).In addition,there were no reductions in the levels of serum indices,including total bilirubin[mean difference(MD)=10.96,95%CI=-3.56-25.49,P=0.14],direct bilirubin(MD=7.37,95%CI=-9.76-24.5,P=0.4),alanine aminotransferase(MD=7.52,95%CI=-0.71-15.74,P=0.07),and aspartate aminotransferase(MD=-4.77,95%CI=-19.98-10.44,P=0.54),after treatment.Publication bias was detected regarding the outcome overall survival;however,the conclusions were not changed after the adjustment.CONCLUSION Placement of stents combined with brachytherapy using^(125)I seeds contributes to a longer stent patency and higher overall survival than placement of conventional stents without extra complications or severe liver damage.Thus,it can be considered an effective and safe treatment for unresectable MOJ.

Effects of Lactobacillus plantarum on gut barrier function in experimental obstructive jaundice

AIM:To investigate the mechanisms of Lactobacillus plantarum(L.plantarum)action on gut barrier in preoperative and postoperative experimental obstructive jaundice in rats.METHODS:Forty rats were randomly divided into groups of sham-operation,bile duct ligation(BDL),BDL +L.plantarum,BDL+internal biliary drainage(IBD),and BDL+IBD+L.plantarum.Ten days after L.plantarum administration,blood and ileal samples were collected from the rats for morphological examination,and intestinal barrier function,liver function,intestinal oxidative stress and protein kinase C(PKC)activity measurement.The distribution and expression of the PKC and tight junction(TJ)proteins,such as occludin,zonula occludens-1,claudin-1,claudin-4,junction adhesion molecule-A and F-actin,were examined by confocal laser scanning microscopy,immunohistochemistry,Western blotting,real-time fluorescent quantitative polymerase chain reaction assay.RESULTS:L.plantarum administration substantially restored gut barrier,decreased enterocyte apoptosis,improved intestinal oxidative stress,promoted the activity and expression of protein kinase(BDL vs BDL+L.plantarum,0.295±0.007 vs 0.349±0.003,P<0.05;BDL+IBD vs BDL+IBD+L.plantarum,0.407±0.046 vs 0.465±0.135,P<0.05),and particularly enhanced the expression and phosphorylation of TJ proteins in the experimental obstructive jaundice(BDL vs BDL+L.plantarum,0.266±0.118 vs 0.326±0.009,P<0.05).The protective effect of L.plantarum was more prominent after internal biliary drainage(BDL+IBD vs BDL +IBD+L.plantarum,0.415±0.105 vs 0.494±0.145,P<0.05).CONCLUSION:L.plantarum can decrease intestinal epithelial cell apoptosis,reduce oxidative stress,and prevent TJ disruption in biliary obstruction by activating the PKC pathway.

Roux-en-Y choledochojejunostomy using novel magnetic compressive anastomats in canine model of obstructive jaundice

BACKGROUND:The traditional hand-sewn Roux-en-Y choledochojejunostomy is technically complicated,and the incidence of postoperative complications has remained high.A set of novel magnetic compressive anastomats was introduced to facilitate choledochojejunostomy and improve the prognosis of patients.METHODS:After ligating the common bile duct for 7 days,16 dogs were randomly divided into two groups (n=8 per group).Anastomats were used in the study group,and the traditional hand-sewn method was used in the control group for standard Roux-en-Y choledochojejunostomy.We compared the operation time,incidence of complications,gross appearance,and pathological disparity in stoma between the two groups in 1-month and 3-month follow-up examinations.RESULTS:The time spent on constructing the anastomosis for the study group was significantly shortened.Although no anastomotic stenosis occurred in the two groups,the narrowing rate of biliary-enteric anastomosis was much higher in the control group.There was one case of bile leakage in the control group,whereas no bile leakage occurred in the study group.A smoother surface,an improved layer apposition,and a lower local inflammatory response were identified in the anastomosis of the study group.CONCLUSION:The structures of the novel magnetic compressive anastomats are simple,and they are time-saving,safe and efficient for performing Roux-en-Y choledocho- jejunostomy procedures in a canine model of obstructive jaundice.

Pathophysiological consequences of obstructive jaundice and perioperative management

Background: Obstructive jaundice is a common problem in daily clinical practice. Understanding completely the pathophysiological changes in obstructive jaundice remains a challenge for planning current and future management.Data sources: A Pub Med was searched for relevant articles published up to August 2016. The effect of obstructive jaundice on proinflammatory cytokines, coagulation status, hemodynamics and organ functions were evaluated.Results: The effects of obstructive jaundice included biliary tree, the hepatic cell and liver function as well as systemic complications. The lack of bile in the gut, the disruption of the intestinal mucosal barrier,the increased absorption of endotoxin and the subsequent endotoxemia cause proinflammatory cytokine production(TNF-α, IL-6). Bilirubin induces systemic inflammatory response syndrome which may lead to multiple organ dysfunction syndrome. The principal clinical manifestations include hemodynamic instability and acute renal failure, cardiovascular suppression, immune compromise, coagulation disorders,nutritional impairment, and wound healing defect. The proper management includes full replacement of water and electrolyte deficiency, prophylactic antibiotics, lactulose, vitamin K and fresh frozen plasma,albumin and dopamine. The preoperative biliary drainage has not been indicated in overall, but only in a few selected cases.Conclusion: The perioperative management is an essential measure in improving the outcome after the appropriate surgical operation in jaundiced patients especially those with malignancy.

Effect of biliary drainage on inducible nitric oxide synthase, CD14 and TGR5 expression in obstructive jaundice rats

AIM: To investigate the effect of biliary drainage on inducible nitric oxide synthase (iNOS), CD14 and TGR5 expression in rats with obstructive jaundice (OJ). METHODS: Male adult Sprague-Dawley rats were randomly assigned to four groups: OJ, sham operation (SH), internal biliary drainage (ID) and external biliary drainage (ED). Rat models were successfully established by two operations and succumbed for extraction of Kupffer cells (KCs) and liver tissue collection on the 8 th and 15 th day. KCs were isolated by in situ hepatic perfusion and digested with collagen Ⅳ, density gradient centrifuged by percoll reagent and purified by cell culture attachment. The isolated KCs were cultured with the endotoxin lipopolysaccharide (LPS) with and without the addition of ursodeoxycholic acid (UDCA). The expression of iNOS, CD14 and bile acid receptor-TGR5 protein in rat liver tissues was determined by immunohistochemistry. The expression of iNOS and CD14 messenger RNA (mRNA) on the isolated KCs was detected by reverse transcription polymerase chain reaction (PCR) and the TGR5 mRNA level in KCs was measured by real-time quantitative PCR. RESULTS: The iNOS protein was markedly expressed in the liver of OJ rats, but rare expressed in SH rats. After relief of OJ, the iNOS expression was decidedly suppressed in the ID group (ID vs OJ, P < 0.01), but obviously increased in rats of ED (ED vs OJ, P=0.004). When interfered only with LPS, the expression of iNOS mRNA by KCs was increased in the OJ group compared with the SH group (P=0.004). After relief of biliary obstruction, the iNOS mRNA expression showed slight changes in the ED group (ED vs OJ, P=0.71), but dropped in the ID group (ID vs OJ, P=0.001). Compared with the simple intervention with LPS, the expressions of iNOS mRNA were significantly inhibited in all four groups after interfered with both LPS and UDCA (P < 0.01, respectively). After bile duct ligation, the CD14 protein expression in rat liver was significantly strengthened (OJ vs SH, P < 0.01), but the CD14 mRNA level by KCs was not up-regulated (OJ vs SH, P=0.822). After relieving the OJ, the expression of CD14 protein was reduced in the ID group (ID vs OJ, P < 0.01), but not reduced in ED group (ED vs OJ, P=0.591). And then the CD14 mRNA expression was aggravated by ED (ED vs OJ, P < 0.01), but was not significantly different between the ID group and the SH and OJ groups (ID vs SH, P=0.944; ID vs OJ, P=0.513, respectively). The expression of TGR5 protein and mRNA increased significantly in OJ rats (OJ vs SH, P=0.001, respectively). After relief of OJ, ID could reduce the expression of TGR5 protein and mRNA to the levels of SH group (ID vs SH, P=0.22 and P=0.354, respectively), but ED could not (ED vs SH, P=0.001, respectively).CONCLUSION: ID could be attributed to the regulatory function of activation of KCs and release of inflammatory mediators.

Biliary drainage for obstructive jaundice caused by unresectable hepatocellular carcinoma: the endoscopic versus percutaneous approach

BACKGROUND: For palliative treatment of the obstructive jaundice associated with unresectable hepatocellular carcinoma (HCC), percutaneous transhepatic biliary drainage (PTBD) or endoscopic retrograde biliary drainage (ERBD) has been performed. PTBD is preferred as an initial procedure. Little is known about the better option for patients with obstructive jaundice caused by unresectable HCC. METHODS: Sixty patients who had received ERBD or PTBD for the palliative treatment of obstructive jaundice caused by unresectable HCC between January 2006 and May 2010 were included in this retrospective study. Successful drainage, drainage patency, and the overall survival of patients were evaluated. RESULTS: Univariate analysis revealed that the overall frequency of successful drainage was higher in the ERBD group (22/29, 75.9%) than in the PTBD group (15/31, 48.4%) (P=0.029); but multivariate analysis showed marginal significance (P=0.057). The duration of drainage patency was longer in the ERBD group than in the PTBD group (82 vs 37 days, respectively, P=0.020). Regardless of what procedure was performed, the median survival time of patients who had a successful drainage was much longer than that of the patients who did not have a successful drainage (143 vs 38 days, respectively, P<0.001).CONCLUSION: Besides PTBD, ERBD may be used as the initial treatment option to improve obstructive jaundice in patients with unresectable HCC if there is a longer duration of drainage patency after a successful drainage.

Protective effects of intravenous anesthetics on kidney tissue in obstructive jaundice

AIM: To evaluate the protective effects on kidney tissue of frequently used intravenous anesthetics (ketamine, propofol, thiopental, and fentanyl) in rats with obstructive jaundice.

Pathophysiology of increased intestinal permeability in obstructive jaundice

Despite advances in preoperative evaluation and postoperative care, intervention, especially surgery, for relief of obstructive jaundice still carries high morbidity and mortality rates, mainly due to sepsis and renal dysfunction. The key event in the pathophysiology of obstructive jaundice-associated complications is endotoxemia of gut origin because of intestinal barrier failure. This breakage of the gut barrier in obstructive jaundice is multi-factorial, involving disruption of the immunologic, biological and mechanical barrier. Experimental and clinical studies have shown that obstructive jaundice results in increased intestinal permeability. The mechanisms implicated in this phenomenon remain unresolved, but growing research interest during the last decade has shed light in our knowledge in the field. This review summarizes the current concepts in the pathophysiology of obstructive jaundice-induced gut barrier dysfunction, analyzing pivotal factors, such as altered intestinal tight junctions expression, oxidative stress and imbalance of enterocyte proliferation and apoptosis. Clinicians handling patients with obstructive jaundice should not neglect protecting the intestinal barrier function before, during and after intervention for the relief of this condition, which may improve their patients’ outcome.

Profile of hepatocyte apoptosis and bile lakes before and after bile duct decompression in severe obstructive jaundice patients

BACKGROUND:Excessive hepatocyte apoptosis and bile lakes in severe obstructive jaundice might impair liver functions.Although decompression of the bile duct has been reported to improve liver functions in animal studies,the mechanism of obstruction differs from that in humans.This study aimed to determine the profiles of hepatocyte apoptosis and bile lakes following bile duct decompression in patients with severe obstructive jaundice in the clinical setting.METHODS:We conducted a 'before and after study' on severe obstructive jaundice patients as a model of inhibition of the excessive process by bile duct decompression.Specimens of liver biopsies were taken before and after decompression of the bile duct and then stained by terminal deoxynucleotide transferase-mediated dUTP nick end-labeling(TUNEL) to identify hepatocyte apoptosis and by hematoxilin-eosin(HE) to identify bile lakes.All measurements were independently done by 2 observers.RESULTS:Twenty-one severe obstructive jaundice patients were included.In all patients,excessive hepatocyte apoptosis and bile lakes were apparent.After decompression,the hepatocyte apoptosis index decreased from 53.1(SD 105) to 11.7(SD 13.6)(P<0.05),and the bile lakes from 23.6(SD 14.8) to 10.9(SD 6.9)(P<0.05).CONCLUSION:Bile duct decompression improves hepatocyte apoptosis and bile lakes in cases of severe obstructive jaundice,similar to the findings in animal studies.

One-step palliative treatment method for obstructive jaundice caused by unresectable malignancies by percutaneous transhepatic insertion of an expandable metallic stent

AIM： To describe a simple one-step method involving percutaneous transhepatic insertion of an expandable metal stent （EMS） used in the treatment of obstructive jaundice caused by unresectable malignancies. METHODS： Fourteen patients diagnosed with obstructive jaundice due to unresectable malignancies were included in the study. The malignancies in these patients were a result of very advanced carcinoma or old age. Percutaneous transhepatic cholangiography was performed under ultrasonographic guidance. After a catheter with an inner metallic guide was advanced into the duodenum, an EMS was placed in the common bile duct, between a point 1 cm beyond the papilla of Vater and the entrance to the hepatic hilum. In cases where it was difficult to span the distance using just a single EMS, an additional stent was positioned. A drainage catheter was left in place to act as a hemostat. The catheter was removed after resolution of cholestasis and stent patency was confirmed 2 or 3 d post-procedure. RESULTS： One-step insertion of the EMS was achieved in all patients with a procedure mean time of 24.4 min. Out of the patients who required 2 EMS, 4 needed a procedure time exceeding 30 min. The mean time for removal of the catheter post-procedure was 2.3 d. All patients died of malignancy with a mean follow-up time of 7.8 mo. No stent-related complication or stent obstruction was encountered. CONCLUSIONS： One-step percutaneous transhepaticinsertion of EMS is a simple procedure for resolving biliary obstruction and can effectively improve the patient＇s quality of life.

Experimental obstructive jaundice alters claudin-4 expression in intestinal mucosa: Effect of bombesin and neurotensin

AIM： To investigate the influence of experimental obstructive jaundice and exogenous bombesin （BBS） and neurotensin （NT） administration on the expression of the tight junction （TJ）-protein claudin-4 in intestinal epithelium of rats. METHODS： Forty male Wistar rats were randomly divided into five groups： Ⅰ = controls, Ⅱ = sham operated,Ⅲ = bile duct ligation （BDL）,Ⅳ = BDL＋BBS （30μg/kg per d）, V = BDL＋NT （300μg/kg per d）. At the end of the experiment on d 10, endotoxin was measured in portal and aortic blood. Tissue sections of the terminal ileum were examined histologically and immunohistochemically for evaluation of claudin-4 expression in intestinal epithelium. RESULTS： Obstructive jaundice led to intestinal barrier failure demonstrated by significant portal and aortic endotoxemia. Claudin-4 expression was significantly increased in the upper third of the villi in jaundiced rats and an upregulation of its lateral distribution was noted. Administration of BBS or NT restored claudin-4 expression to the control state and significantly reduced portal and aortic endotoxemia. CONCLUSION： Experimental obstructive jaundice increases claudin-4 expression in intestinal epithelium,which may be a key factor contributing to the disruption of the mucosal barrier. Gut regulatory peptides BBS and NT can prevent this alteration and reduce portal and systemic endotoxemia.

Decreased hepatic peroxisome proliferator-activated receptor-γ contributes to increased sensitivity to endotoxin in obstructive jaundice

AIM: To investigate the role of hepatic peroxisome proliferator-activated receptor-γ (PPAR-γ) in increased susceptibility to endotoxin-induced toxicity in rats with bile duct ligation during endotoxemia.METHODS: Male Sprague-Dawley rats were subjected to bile duct ligation (BDL). Sham-operated animals served as controls. DNA binding were determined by polymerase chain reaction, Western blotting analysis,and electrophoretic mobility shift assay, respectively.BDL and sham-operated rats received a non-lethal dose of intraperitoneal lipopolysaccharide (LPS) injection (3 mg/kg, i.p.). Additionally, the potential beneficial effects of the PPAR-γ agonist rosiglitazone were determined in BDL and sham-operated rats treated with a non-lethal dose of LPS. Survival was assessed in BDL rats treated with a non-lethal dose of LPS and in sham-operatedrats treated at a lethal dose of LPS (6 mg/kg, i.p.).RESULTS: PPAR-γ activity in rats undergoing BDL wassignificantly lower than in the sham-controls. Hepatic PPAR-γ gene expression was downregulated at both them RNA and protein levels. In a parallel group, serumlevels of pro-inflammatory cytokines were nearly unde-tectable in the sham-operated rats. When challenged with a non-lethal dose of LPS (3 mg/kg), the BDL ratshad approximately a 2.4-fold increase in serum IL-6,a 2.7 fold increase in serum TNF-α, 2.2-fold increasein serum IL-1 and 4.2-fold increase in serum ALT. Thesurvival rate was significantly lower as compared with that in sham-operated group. Additionally, rosiglitazone significantly reduced the concentration of TNF-α, IL-1β, IL-6 and ALT in sham-operated rats, but not in BDL rats, in response to LPS (3 mg/kg). Also, the survival was improved by rosiglita zone in sham-operated rats challenged with a lethal dose of LPS, but not in BDL rats, even with a non-lethal dose of LPS (3 mg/kg).CONCLUSION: Obstructive jaundice downregulates hepatic PPAR-γ expression, which in turn may contributeto hypersensitivity towards endotoxin.