Search

Autoimmune pancreatitis (AIP) is a rare entity that is extremely uncommon in children. Its diagnosis is also a clinical challenge. This form of chronic pancreatitis often presents itself with obstructive jaundice and/or a pancreatic mass and it is sometimes misdiagnosed as pancreatic cancer. We describe the case of a 13-year-old boy with obstructive jaundice and a 4 cm mass in the head of the pancreas that was diagnosed as AIP with associated ulcerative colitis., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2018. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Obstructive jaundice (OJ) patients with cholangitis are prone to sepsis; however, the underlying mechanisms are still not clear and need to be clarified., Methods: Analyzing all available published data related to the title of this article., Results: OJ leads to absence of gut luminal bile and accumulation of hepatic and circulating bile acids. Absence of gut luminal bile deprives the gut from its antiinflammatory, endotoxin-binding, bacteriostatic, mucosal-trophic, epithelial tight-junction maintaining, and gut motility-regulating effects, leading to gut bacterial overgrowth, mucosal atrophy, mucosal tight-junction loss, and gut motility dysfunction. These alterations promote intestinal endotoxin and bacterial translocation (BT) into portal and systemic circulation. Gut BT triggers systemic inflammation, which can lead to multiple organ dysfunctions in OJ. The accumulation of hepatic and circulating bile acids kills/damages hepatocyte and Kupffer cells, and it also significantly decreases the number of liver natural killer T-cells in OJ. This results in impaired hepatic and systemic immune function, which facilitates BT. In addition, neutralizing bile HMGB1 can reverse endotoxemic bile-induced gut BT and mucosal injury in mice, suggesting that bile HMGB1 in OJ patients can be responsible for internal drainage-related clinical complications. Moreover, the elevated circulating HMGB1 level may contribute to multiple organ injuries, and it might also mediate gut BT in OJ., Conclusions: HMGB1 may significantly contribute to systemic inflammation and multiple organ dysfunctions in OJ., (Copyright © 2018 Elsevier Inc. All rights reserved.)

BACKGROUND Obstructive jaundice is a serious, life-threatening condition that can lead to death as a result of sepsis and multiorgan failure due to bacterial translocation. Treatment should be started as soon as possible after diagnosis. MATERIAL AND METHODS Forty 24-week-old male Sprague Dawley rats, with an average weight of 250 g to 300 g, were included in this study. The rats were randomly placed into five groups, each group consisted of eight rats. The sham group underwent only common bile duct (CBD) dissection and no ligation was performed. CBD ligation was applied to the other groups. After the operation, one CBD group was fed with rat chow only, the others were fed with rat chow supplemented with honey, or immunonutrients, or honey plus immunonutrients. After 10 to 12 days, all rats were sacrificed; blood and tissue samples were collected for biochemical, microbiological, and histopathological evaluation. RESULTS In the groups that were fed with honey and immunonutrients, alanine aminotransferase (ALT) levels were decreased significantly compared to the other groups. Statistically significant differences were detected in terms of bacterial translocation (BT) rates among liver and spleen samples, and laboratory values of serum, except for MLNs of the BDL+HI group, when compared to other groups. We found mean mucosal thickness of ileum samples have been improved notably in the BDL+HI group compared to the other groups, especially compared to the C/BDL group. CONCLUSIONS Immunonutrition applied with honey had immunostimulant effects, decreased BT due to an additive effect, and had positive effects on intestinal mucosa.

Objective: To evaluate the correlation between the change of immune system function before and after the treatment of malignant obstructive type jaundice (MOJ) treated with a biliary stent., Patients and Methods: 148 patients who were admitted to the Department of Digestive System for malignant obstructive jaundice were selected according to the standardized criterion. Amongst the total sample size, 78 were male patients and 70 were female patients, with an average age of (43.6 ± 5.5) years. After admission, the patients completed the blood routine examination and received biliary stent treatment to relieve the sign and symptoms of jaundice. Follow-up observation included total white blood cells, CD4+T cell count, CD8+T cell count, the ratio of CD4+/CD8, neutrophil counts neutrophils percentage, total bilirubin, free bilirubin, alanine aminotransferase (ALT), and inflammatory factors., Results: After three weeks of follow-up visit, CD4+T lymphocyte absolute value of patients markedly increased compared with that of pre-operation, and the difference had statistical significance (p < 0.05). The total bilirubin, free bilirubin, ALT, and inflammatory factors, such as hs-CRP, TNF-α in plasma of patients was significantly lower than that before the operation and the difference was statistically significant (p < 0.05). After six weeks of follow-up visit, the ratio of CD4+/CD8+ increased and the difference had statistical significance (p < 0.05) compared with that before biliary stent implantation. However, the white blood cell and neutrophil granulocyte did not improve significantly. It was found that CD4+/CD8+T lymphocyte had relation with the level of hs-CRP., Conclusions: The patients with the (MOJ) treated with implanted biliary stent revealed relive in the obstruction of the biliary tract, which will further significantly improve the cholestasis. The ratio of CD4+/CD8+T lymphocyte increased, which will improve the immune system function of the patients, decreases the possibility of infection, and improves the overall survival quality.

This prospective observational study investigated monocyte cytokine responses to lipopolysaccharide (LPS) in patients with obstructive jaundice (OJ) before and after endoscopic biliary drainage. Dendritic cell (DC) subsets and their expression of co-stimulatory molecules were also studied. Forty patients with OJ and ten non-jaundiced patients with normal gastroscopy findings were recruited. Ten healthy volunteers provided control blood samples for immunological assays. Patients with OJ had blood and duodenal mucosa sampled at the time of endoscopic retrograde cholangiopancreatography (ERCP) and further blood sampled during the recovery phase. Monocyte cytokine responses to LPS, DC subsets and co-stimulatory molecule expression were compared with controls. Duodenal morphology and occludin expression were also assessed. Monocytes obtained before ERCP from jaundiced patients demonstrated reduced cytokine responses to endotoxin compared with controls (IL-1β: 2678 compared with 4631 pg/ml, P=0.04 and IL-6: 3442 compared with 6157 pg/ml, P=0.002). Monocytes from patients with malignancy had poorer responses to endotoxin than from those with benign OJ (IL-1β: 2025 compared with 3332 pg/ml, P=0.001). After ERCP, the secretion of inflammatory cytokines by monocytes obtained from jaundiced patients increased (IL-1β: 2150 compared with 2520 pg/ml, P=0.03 and IL-6: 2488 compared with 3250 pg/ml, P=0.01). Occludin expression (85 compared with 95%, P=0.004) and mean duodenal villus height (334 compared with 404 μm, P=0.03) were lower in jaundiced patients. Before biliary drainage, patients with OJ had a higher percentage of myeloid dendritic cells (mDCs) and greater mDC expression of CD40 (P=0.04) and CD86 (P=0.04). Monocytes from patients with OJ had lower proinflammatory cytokine secretion in response to LPS, an effect reversed following biliary drainage., (© 2016 The Author(s).)

The results of surgical treatment of 137 patients, suffering obturation jaundice of non-tumoral etiology, were analyzed. In all the patients the cause of obturation jaundice was choledocholithiasis. Roncoleukin was infused intravenously additionally in a complex of therapy. A degree of hepatic dysfunction was determined, taking into account the cholestasis markers. In 23 patients purulent cholangitis have occurred on background of obturation jaundice. Concentration of cytokins TNF-α, IFN-γ, IL-1, IL-2, IL-4, IL-6, IL-10 in sera were determined, using immunoassay analysis. The cytokins dysbalance severity preoperatively and dynamics of its changes have depended upon the hepatic dysbalance degree and presence of purulent cholangitis; a dysbalance is deeper, when the hepatic dysfunction is higher. Application of pathogenetically substantiated purposeful cytokinotherapy, including roncoleukin, have promoted the cytokins dysbalance elimination and improvement of the patients treatment results.

The article analyzed the results of surgical treatment of 137 patients with obstructive jaundice of benign genesis. An immune status was studied in serum in dynamics before surgery. The rates of CD3, CD4, CD8, CD19, Ig A, M, G were determined on the first, third, seventh and fourteenth days after operation. The levels of TNFα, IFNγ, IL-2, IL-6, IL-4, IL-10 were investigated in serum and at the same time TNFα, IL-4, IL-6 were noted in the bile duct and IL-6 - in urine. Obstructive jaundice of cholelithiс genesis is characterized by disbalance of immune and cytokine status. The depth of disbalance depends on the degree of hepatic dysfunction and presence of purulent cholangitis. The directed cytokine therapy by ronkoleykin influenced positively on elimination of disbalance in immune and cytokine status and this therapy improved results of surgery in postoperative period.

Efficacy of the ozonotherapy application as an important component of complex treatment in purulent cholangitis (PCH) was studied. In choledocholithiasis (without infectioning of bile) ozonotherapy may be prescribed as additional component at complex treatment. In PCH ozonotherapy application have promoted the improvement of laboratory indices in 6.6 times, comparing with such, occurring after basic therapy.

Immunoglobulin G4 related disease (IgG4-RD) has been recognized since early 2000s as an entity comprising a set of inflammatory diseases with common histopathological features. The disease may affect almost all organs and tissues, and often occurs in a subacute fashion in males over 50 years as a mass or diffuse enlargement of affected organs. The histopathological appearance is characterized by a lymphoplasmacytic infiltration with predominantly IgG4-positive plasma cells and progressive fibrosis. Its clinical and radiological features can make the distinction with a malignancy difficult. The disease responds well to systemic glucocorticoids however with a high rate of recurrence after treatment discontinuation.

Aim: To observe the protective effect of glucagon-like peptide-2 (GLP-2) on the intestinal barrier of rats with obstructive jaundice and determine the possible mechanisms of action involved in the protective effect., Methods: Thirty-six Sprague-Dawley rats were randomly divided into a sham operation group, an obstructive jaundice group, and a GLP-2 group; each group consisted of 12 rats. The GLP-2 group was treated with GLP-2 after the day of surgery, whereas the other two groups were treated with the same concentration of normal saline. Alanine aminotransferase (ALT), total bilirubin, and endotoxin levels were recorded at 1, 3, 7, 10 and 14 d. Furthermore, on the 14(th) day, body weight, the wet weight of the small intestine, pathological changes of the small intestine and the immunoglobulin A (IgA) expressed by plasma cells located in the small intestinal lamina propria were recorded for each group., Results: In the rat model, jaundice was obvious, and the rats' activity decreased 4-6 d post bile duct ligation. Compared with the sham operation group, the obstructive jaundice group displayed increased yellow staining of abdominal visceral serosa, decreased small intestine wet weight, thinning of the intestinal muscle layer and villi, villous atrophy, uneven height, fusion, partial villous epithelial cell shedding, substantial inflammatory cell infiltration and significantly reduced IgA expression. However, no significant gross changes were noted between the GLP-2 and sham groups. With time, the levels of ALT, endotoxin and bilirubin in the GLP-2 group were significantly increased compared with the sham group (P < 0.01). The increasing levels of the aforementioned markers were more significant in the obstructive jaundice group than in the GLP-2 group (P < 0.01)., Conclusion: GLP-2 reduces intestinal mucosal injuries in obstructive jaundice rats, which might be attributed to increased intestinal IgA and reduced bilirubin and endotoxin.

Background: Although preoperative biliary drainage in jaundiced patients is controversial, external biliary drainage (EBD) is beneficial for infection control in patients with biliary cancers. When EBD is performed, additional bile replacement (BR) has the benefit of improving impaired intestinal barrier function, but the detailed mechanism remains unknown. We examined the effect of bile replacement on immune functions over the duration of BR in jaundiced patients., Methods: Fifteen patients were enrolled into this prospective study. BR was started soon after the total serum bilirubin concentration reached 5.0 mg/dl and was continued for 14 days. Drained bile was given two times orally (2 × 100 ml/day). Concanavalin A (Con A)- and phytohemagglutinin (PHA)-stimulated lymphocyte proliferation and serum diamine oxidase (DAO) activity were measured before starting and during BR. Twenty patients with EBD and no BR were analyzed as a control group., Results: Serum liver enzymes, prothrombin time-international normalized ratio (PT-INR), and responses to Con A and PHA gradually improved over the 14 days of BR, but percentages of lymphocytes and DAO levels did not. PT-INR, and Con A and PHA responses did not improve during EBD in the control group. PT-INR significantly decreased in patients with a greater fraction of their drained bile replaced., Conclusions: Our results indicate that preoperative BR using as large a quantity of bile as possible is useful for improving blood coagulability and cellular immunity in patients with EBD.

Abdominal tuberculosis manifesting as isolated lymphadenopathy is rare, particularly in children. Tuberculous involvement of the pancreatic head and peripancreatic area can simulate a neoplasm of the pancreatic head. To our knowledge, obstructive jaundice caused by tuberculous lymphadenopathy has not been reported in children or adolescents. Here we present radiologic findings in a case of tuberculous lymphadenopathy that mimicked malignancy of the pancreatic head and caused obstructive jaundice in an immunocompetent adolescent.

Background & Aims: Chronic liver disease is characterized by fibrosis that may progress to cirrhosis. Nucleotide oligomerization domain 2 (Nod2), a member of the Nod-like receptor (NLR) family of intracellular immune receptors, plays an important role in the defense against bacterial infection through binding to the ligand muramyl dipeptide (MDP). Here, we investigated the role of Nod2 in the development of liver fibrosis., Methods: We studied experimental cholestatic liver disease induced by bile duct ligation or toxic liver disease induced by carbon tetrachloride in wild type and Nod2(-/-) mice., Results: Nod2 deficiency protected mice from cholestatic but not toxin-induced liver injury and fibrosis. Most notably, the hepatic bile acid concentration was lower in Nod2(-/-) mice than wild type mice following bile duct ligation for 3 weeks. In contrast to wild type mice, Nod2(-/-) mice had increased urinary excretion of bile acids, including sulfated bile acids, and an upregulation of the bile acid efflux transporters MRP2 and MRP4 in tubular epithelial cells of the kidney. MRP2 and MRP4 were downregulated by IL-1β in a Nod2 dependent fashion., Conclusions: Our findings indicate that Nod2 deficiency protects mice from cholestatic liver injury and fibrosis through enhancing renal excretion of bile acids that in turn contributes to decreased concentration of bile acids in the hepatocyte., (Copyright © 2014 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.)

We describe a 42-year-old man who presented with painless obstructive jaundice, organomegaly and lymphadenopathy. Biopsy of the ampulla of Vater revealed the presence of increased populations of plasma cells which stained positively for immunoglobulin G4. He was treated with prednisolone and demonstrated significant clinical improvement 1 month later. A further case is described and a review of the literature is also provided., (© 2013 The Authors International Journal of Rheumatic Diseases © 2013 Asia Pacific League of Associations for Rheumatology and Wiley Publishing Asia Pty Ltd.)

Obstructive jaundice (OJ) increases the risk of liver injury and sepsis, leading to increased mortality. Cholestatic liver injury is associated with a downregulation of hepcidin expression levels. In fact, hepcidin has an important antimicrobial effect, especially against Escherichia coli. It is unknown whether supplementing recombinant hepcidin is effective in alleviating cholestasis-induced liver injury and mortality in mice with superimposed sepsis. A mouse model of cholestasis was developed using extrahepatic bile duct ligation for 3 days. In addition, sepsis due to E. coli 0111:B4 lipopolysaccharide (LPS) was induced in the model. The serum levels of total bilirubin, AST, ALT, and LDH and the mRNA levels of IL-1β, TNF-α, and MCP-1 in the liver were significantly higher in the OJ mice receiving LPS than in the sham-operated mice receiving LPS. Compared to the OJ mice receiving LPS, the hepcidin-pretreated OJ mice receiving LPS showed a significant decrease in the above mentioned parameters, as well as a reversal in the downregulation of LC3B-II and upregulation of cleaved caspase-3; this, in turn, led to significantly decreased lethality in 24h. In conclusion, these results indicate that hepcidin pretreatment significantly reduced hepatic proinflammatory cytokine expression and liver injury, leading to reduced early lethality in OJ mice receiving LPS. Enhanced autophagy and reduced apoptosis may account for the protective effects of hepcidin., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Although obstructive jaundice has been associated with a predisposition toward infections, the effects of bile duct ligation (BDL) on bulk intrahepatic T cells have not been clearly defined. The aim of this study was to determine the consequences of BDL on liver T cell phenotype and function. After BDL in mice, we found that bulk liver T cells were less responsive to allogeneic or syngeneic Ag-loaded dendritic cells. Spleen T cell function was not affected, and the viability of liver T cells was preserved. BDL expanded the number of CD4(+)CD25(+)Foxp3(+) regulatory T cells (Treg), which were anergic to direct CD3 stimulation and mediated T cell suppression in vitro. Adoptively transferred CD4(+)CD25(-) T cells were converted into Treg within the liver after BDL. In vivo depletion of Treg after BDL restored bulk liver T cell function but exacerbated the degrees of inflammatory cytokine production, cholestasis, and hepatic fibrosis. Thus, BDL expands liver Treg, which reduce the function of bulk intrahepatic T cells yet limit liver injury.

History and Admission Findings: One month after a first manifestation of a hepatitis A infection and transaminases had become normal, a 44-year-old woman again became jaundiced with accompanied by weakness, nausea and nocturnal sweating., Investigations: Laboratory tests again showed features of hepatitis with decreased synthetic liver function and hyperbilirubinemia, changes which persisted for 12 weeks. Serological and virological studies revealed a positive test for anti-hepatitis A virus (HAV) IgM and HAV-RNA was detected in the stool., Diagnosis, Treatment and Course: These tests demonstrated two rare features of hepatitis A, namely a prolonged biphasic course combined with cholestasis form. In addition a hemolytic anaemia developed., Conclusion: The severity of a relapse of hepatitis A varies: in this case it was more severe than the initial manifestation. The reasons for the different courses of hepatitis A infection remain unclear., (© Georg Thieme Verlag KG Stuttgart · New York.)

Introduction: Cholemia and bacterial translocation with portal endotoxemia are integral in the pathogenesis of obstructive jaundice (OJ). There is sufficient experimental data about hemodynamic and histopathological consequences of OJ. In contrast, pathological information of renal changes in patients with OJ is still lacking. Therefore; the primary objective of this prospective study is to show the specific histopathological changes in kidneys of patients with short-term biliary tract obstruction receiving a standard perioperative medical treatment protocol., Materials and Methods: Twenty consecutive patients with biliary obstruction were included in the study. Fluid replacement, prevention of biliary sepsis, and portal endotoxemia were mainstays of the perioperative treatment protocol. Fluid and electrolyte balance was maintained by twice daily body weight calculations, central venous pressure, and mean arterial pressure monitoring. Renal function was assessed by glomerular filtration rate estimation by modification of diet in renal disease-7 formula. Kidney biopsy evaluation was focused on tubular changes, thrombotic microangiopathy, endothelial damage, and peritubular capillary (PTC) dilatation with or without C4d staining. Fresh frozen sections were evaluated with immunofluorescence microscopy for glomerular IgG, IgA, IgM, C3, and C1q staining., Results: The mean duration of OJ was 15.5 ± 1.4 days. Body weight increased before surgery through volume expansion (P = 0.001). All patients have shown mean arterial pressure ≥ 70 and ≤ 120 mmHg and renal function was very well preserved in all but one subject during the perioperative period. Despite those favorable figures, dilatation of peritubular venules and acute tubular necrosis were shown synchronously in all cases. C4d staining in PTC and arterioles and thrombotic microangiopathy were entirely absent in the study group. Immune complex deposits in PTCs and in glomeruli were not detected. Three patients had isolated glomerular C4d deposition without accompanying thrombotic microangiopathy and IgG, IgA, IgM, C3, and C1q staining of glomerular capillaries in I immunofluorescence microscopy., Discussion: This study is the first in the literature to address the histopathological changes that occur in humans with short-term biliary obstruction. Acute tubular necrosis and venous dilatation was observed in all biopsies, without exception, despite the maintenance of strict volume control in all patients. The adequacy of volume control may not be implicated in those results; rather a possible mechanism related to untrapped endotoxin in the gut lumen or systemic circulation might lead to prolonged PTC dilatation and hypoperfusion with synchronous acute tubular necrosis. Absolute recovery of renal function in all patients and the demonstration of solitary acute tubular necrosis with no microvascular-glomerular-interstitial inflammation or injury, suggests that the perioperative treatment regime in this study is fairly efficacious in short-term OJ.

Autoimmune or immunoglobulin G subtype (IgG4) pancreatitis is a newly recognised clinical entity and is an important differential diagnosis for patients presenting with obstructive jaundice. Knowledge of autoimmune pancreatitis (AIP) continues to evolve both for pathogenesis and management; however diagnosis is often not straightforward or even considered, therefore a high index of suspicion remains an important tool for the treating physician. The six cases presented illustrate both the difficulties in diagnosis as well as management of this condition.

Autoimmune pancreatitis (ALP) represents a distinct form of chronic pancreatitis initially described in Japan but now reported worldwide. AIP often presents with obstructive jaundice/pancreatic mass as well as pancreatic exocrine and endocrine insufficiency. Histologically, it is characterised by a lymphoplasmacytic infiltrate with fibrosis. The disease responds readily to steroids in 70-80% of cases. Given the absence of unified diagnostic criteria, the diagnosis of AIP proves difficult. In particular, distinguishing ALP from pancreatic or biliary cancer remains a challenging task. In order to avoid unnecessary resections for an otherwise benign and easily treatable condition, it is urgent to refine diagnostic criteria and to reach an international consensus.

Autoimmune pancreatitis (AIP) has been extensively reported from Japan, Europe, and the United States. Whereas the descriptions of AIP from Japan have predominantly been based on the presence of a distinct clinical phenotype, reports from Europe and the United States describe at least 2 histopathologic patterns in patients' condition currently diagnosed as AIP, viz, lymphoplasmacytic sclerosing pancreatitis (LPSP) and idiopathic duct centric pancreatitis (IDCP) or granulocyte epithelial lesion (GEL)-positive pancreatitis. Although the 2 entities share common histopathologic features (periductal lymphoplasmacytic infiltration and peculiar periductal fibrosis), expert pathologists can accurately distinguish them based on other unique histopathologic features. Clinically, the 2 entities have similar clinical presentation (obstructive jaundice/pancreatic mass and a dramatic response to steroids) but differ significantly in their demography, serological characteristics, other organ involvement, and disease relapse. While LPSP is associated with elevation in titers of nonspecific autoantibodies and serum IgG4 levels, IDCP does not have definitive serological autoimmune markers. All experts agreed that the clinical phenotypes associated with LPSP and IDCP should be nosologically distinguished; however, their terminology was debated. Whereas most experts agreed that the entities should be referred to as type 1 and type 2 AIP, respectively, others had concerns regarding use of the term "autoimmune" to describe IDCP.

Background: Ringer's ethyl pyruvate solution (REPS) has been shown to ameliorate liver injury in a murine model of extrahepatic cholestasis. The goal of the present investigation was to gain additional information about whether infusing REPS instead of Ringer's lactate solution (RLS) after inducing obstructive jaundice would be beneficial to intestinal barrier function, inflammatory response, and oxidative stress., Methods: Male Sprague Dawley rats were divided into three groups: Group Sham (n=6), sham-treated controls; Group RLS (n=9), common bile duct ligation (CBDL) plus RLS; and Group REPS (n=9), CBDL plus REPS. On 14 d after BDL, the rats were sacrificed and intestinal permeability was analyzed. Ileal IL-6 and TNF-alpha levels, malondialdehyde (MDA), glutathione (GSH), myeloperoxidase (MPO), and NF-kappaB activity were determined. Histologic examination and apoptosis of ileum were also examined., Results: Relative to sham-treated controls, CBDL in RLS-treated rats were associated with increased intestinal permeability to FITC-labeled dextran (4.51+/-0.85 versus 0.44+/-0.18, P<0.01), histopathologic damage and apoptosis (68.4+/-13.4 versus 6.7+/-1.9 pre-1000 villi cells, P<0.01). IL-6 and TNF-alpha level, MDA, MPO, and NF-kappaB activity in ileal tissues were also promoted, along with decreased GSH levels. Treatment with REPS significantly decreased intestinal permeability (3.37+/-0.71, P<0.01) and apoptosis (42.8+/-14.3 pre-1000 villi cells, P<0.01). Other changes were also significantly attenuated by treatment with REPS after CBDL., Conclusions: The present study demonstrates that administration of REPS, but not RLS, maintains intestinal barrier function and reduces intestinal oxidative damage, inflammatory response, and apoptosis in cholestatic rats. This effect of ethyl pyruvate may be useful for preventing intestinal injury in patients with biliary obstruction., (Crown Copyright (c) 2010. Published by Elsevier Inc. All rights reserved.)

Although patients with obstructive jaundice are susceptible to bacterial infections and cancers, the mechanisms remain to be elucidated. In the present study, liver mononuclear cells (MNCs) of bile duct-ligated (BDL) mice were immunologically assessed. Liver natural killer T cells were greatly decreased within 24 h after BDL. Upon injection of Escherichia coli (E. coli; 10 colony-forming units) at 7 days after the procedure, all BDL mice had died, but no sham mice died. Consistently, an overgrowth of E. coli was seen in the livers of BDL mice. Although the serum IL-12 and IL-18 levels after E. coli challenge in BDL mice were higher than those in sham mice, the IFN-gamma level was greatly suppressed. However, exogenous IFN-gamma injection significantly increased BDL mouse survival after E. coli challenge. Furthermore, liver MNC of BDL mice exhibited a lower cytotoxic activity against tumors, and BDL mice intravenously injected with liver metastatic EL-4 cells showed markedly increased EL-4 metastases. The total bile acids, as well as the bile acid fractions, increased in the sera and liver. IFN-gamma production by liver MNC from normal mice stimulated with LPS in vitro was inhibited by the addition of bile acids, whereas, conversely, the production of IL-12 and IL-18 increased. In conclusion, liver natural killer T cells were diminished in BDL mice, and the function of liver MNC (IFN-gamma production) was also impaired presumably due to increased bile acids. This may partly explain the increased susceptibility of BDL mice to bacterial infections and tumor metastasis.

The authors have studied indices of the humoral immunity with mechanical jaundice of nonneoplastic genesis. Disorders of immune status of patients with bilious ways obturation, which were characterized by concentration increase IgG in 1,6 times, IgA--in 1,3 times and IgM--in 1,7 times of the level of circulating immune complexes--in 1,6 times and decrease in fractional index and fractional number in 2 and 1,7 times accordingly. The study has shown principle efficiency of enterosorption in patients with mechanical jaundice in restoration of indices of the humoral immunity. It was seen more considerably with application of chitin-contained active substance, mycotin. It has allowed improving functional ability of the liver, especially its synthesizing function and hydroxylation processes in hepatic cells.

Autoimmune pancreatitis (AIP) has been extensively reported from Japan, Europe and the USA. While the descriptions of AIP from Japan have predominantly been based on the presence of a distinct clinical phenotype, reports from Europe and the USA describe at least 2 histopathologic patterns in patients diagnosed with AIP, namely lymphoplasmacytic sclerosing pancreatitis (LPSP) and idiopathic duct-centric pancreatitis (IDCP) or granulocytic epithelial lesion- positive pancreatitis. While the 2 entities share common histopathologic features (periductal lymphoplasmacytic infiltration and peculiar periductal fibrosis), expert pathologists can accurately distinguish them on the basis of other unique histopathologic features. Clinically, the 2 entities have a similar presentation (obstructive jaundice/pancreatic mass and a dramatic response to steroids), but they differ significantly in their demography, serology, involvement of other organs and disease relapse rate. While LPSP is associated with elevation of titers of nonspecific autoantibodies and serum IgG4 levels, IDCP does not have definitive serologic autoimmune markers. All experts agreed that the clinical phenotypes associated with LPSP and IDCP should be nosologically distinguished; however, their terminology was controversial. While most experts agreed that the entities should be referred to as type 1 and type 2 AIP, respectively, others had concerns regarding use of the term 'autoimmune' to describe IDCP. and IAP., (Copyright © 2011 S. Karger AG, Basel.)

Background: CA19-9 is a carbohydrate tumor-associated antigen which is frequently upregulated in pancreatobiliary neoplasia. However, it may also be elevated in patients with jaundice in the absence of a tumor due to biliary obstruction, and in other non-hepato-pancreatico-biliary conditions. This study aimed to evaluate whether CA19-9 levels could accurately differentiate between benign and malignant pancreatobiliary disease., Methods: All patients referred to a single surgeon for investigation of pancreaticobiliary disease in 2003 in whom a firm diagnosis had been established were included. For malignant disease, a histological diagnosis was required but for benign disease a firm radiological diagnosis was deemed adequate. The patients were divided into 4 categories: pancreatic adenocarcinoma (PCa); cholangiocarcinoma (CCa); chronic pancreatitis (CP) and biliary calculous disease (Calc). Bilirubin and alkaline phosphatase levels corresponding to the point of assessment of CA19-9 were also noted., Results: Final diagnoses were made of pancreatic adenocarcinoma (PCa, n=73), cholangiocarcinoma (CCa, n=19), ampullary carcinoma (Amp, n=7), neuroendocrine carcinoma (Neu, n=4), duodenal carcinoma (Duo, n=3), chronic pancreatitis (CP, n=115), and biliary calculous disease (Calc, n=27). Median CA19-9 levels (U/ml) were: PCa, 653; CCa, 408; Duo, 403; Calc, 27; CP, 19; Neu, 10.5; Amp, 8 (reference range: 0-37). The CA19-9 levels were significantly greater for malignant than for benign disease, could differentiate PCa from CCa/Duo, and were significantly higher in unresectable than in resectable PCa. The sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) for CA19-9 were 84.9%, 69.7%, 67.7% and 86.1%, respectively. A ROC analysis provided an area under the curve for CA19-9 of 0.871 (0.820-0.922), giving an optimal CA19-9 of 70.5 U/ml for differentiating benign from malignant pathology. Using this cut-off, the sensitivity was 82.1%, while specificity, PPV and NPV improved to 85.9%, 81.3% and 86.5%, respectively. When standard radiology was included (US/CT/MRCP) in the decision process, the results improved to 97.2%, 88.7%, 86.6%, and 97.7%. For benign disease, the CA19-9 correlated directly with the serum bilirubin, but for malignant disease, CA19-9 levels were elevated independent of the bilirubin level., Conclusions: CA19-9 is useful in the differentiation of pancreatobiliary disease and when using an optimized cut-off and combining with routine radiology, the diagnostic yield is improved significantly, thus stressing the importance of a multi-disciplinary approach to pancreatobiliary disease.

Background: Autoimmune pancreatitis (AIP) is a relatively newly recognized type of pancreatitis that is characterized by diffuse or focal swelling of the pancreas due to lymphoplasmacytic infiltration and fibrosis of the pancreatic parenchyma., Material and Methods: A PubMed literature search was performed using the keywords "autoimmune pancreatitis". Sometimes, bibliographies were cross-referenced and related article searches were performed once an article of interest was identified., Results: Pathologically, AIP shows narrowing of the pancreatic ducts and the intrapancreatic portion of the common bile duct. Obstructive jaundice is a common symptom at presentation, and pancreatic cancer represents an important clinical differential diagnosis. In late stages of the disease, the normal pancreatic parenchyma is often replaced by large amounts of fibrosis. Histologically, there seem to be two subtypes of the disease-one showing infiltration with IgG4-positive plasma cells but lacking granulocytic epithelial lesions (GELs), the other showing GELs but lacking strong IgG4 positivity. AIP is in at least some instances the pancreatic manifestation of a clinicopathological entity of IgG4-related systemic sclerosing disease. On the basis of pancreatic imaging, together with serological measurement of IgG4 and evaluation of other organ involvement, many AIP patients can be identified. The remaining patients require further diagnostic work-up. In these patients, pancreatic core needle biopsy and, as AIP responds to steroid treatment, also a trial with steroids, can help to differentiate AIP from pancreatic cancer. OUTLOOK AND DISCUSSION: This review presents the pathological, radiologic and laboratory findings of AIP. Moreover, the treatment and pathogenesis are discussed.

Background & Aims: Immunoglobulin (Ig)G4-associated cholangitis (IAC) is the biliary manifestation of a steroid-responsive multisystem fibroinflammatory disorder in which affected organs have a characteristic lymphoplasmacytic infiltrate rich in IgG4-positive cells. We describe clinical features, treatment response, and predictors of relapse in IAC and compare relapse rates in IAC with intrapancreatic vs proximal bile duct strictures., Methods: We reviewed clinical, serologic, and imaging characteristics and treatment response in 53 IAC patients., Results: IAC patients generally were older (mean age, 62 y) men (85%), presenting with obstructive jaundice (77%) associated with autoimmune pancreatitis (92%), increased serum IgG4 levels (74%), and abundant IgG4-positive cells in bile duct biopsy specimens (88%). At presentation, biliary strictures were confined to the intrapancreatic bile duct in 51%; the proximal extrahepatic/intrahepatic ducts were involved in 49%. Initial presentation was treated with steroids (n = 30; median follow-up period, 29.5 months), surgical resection (n = 18; median follow-up period, 58 months), or was conservative (n = 5; median follow-up period, 35 months). Relapses occurred in 53% after steroid withdrawal; 44% relapsed after surgery and were treated with steroids. The presence of proximal extrahepatic/intrahepatic strictures was predictive of relapse. Steroid therapy normalized liver enzyme levels in 61%; biliary stents could be removed in 17 of 18 patients. Fifteen patients treated with steroids for relapse after steroid withdrawal responded; 7 patients on additional immunomodulatory drugs remain in steroid-free remission (median follow-up period, 6 months)., Conclusions: IAC should be suspected in unexplained biliary strictures associated with increased serum IgG4 and unexplained pancreatic disease. Relapses are common after steroid withdrawal, especially with proximal strictures. The role of immunomodulatory drugs for relapses needs further study.

The aim of the article was the evaluation of the efficiency of decompression of biliary tracts and determination of optimal period of external draining. The biochemical rates of functional state of liver, dynamic of factors of humeral nonspecific defense in blood serum and bile, in 197 patients with obstructive jaundice were investigated. Concurrently, the dynamic of nonspecific defense reaction changes in infected hepatic bile, changes of amylase, pH, and bile hypertensia were studied. The obtained data are used to determine optimal period of external draining of biliary tracts. The investigation showed that early decompression of biliary tracts allows fast restore of the liver function. Restoration of natural resistance and their positive dynamic depends on the period of performance of external draining; to a lesser degree it depends on the method of performance.

Several experimental studies of obstructive jaundice (OJ) have shown the presence of immunosuppressive state associated with the rise of tumor necrosis factor-alpha (TNF-alpha) concentration in plasma. The present study evaluates the impact of anti-TNF- alpha administration or bile duct drainage on the inflammatory response, liver injury and renal insufficiency in obstructed rats. OJ was induced by the ligation of bile duct in Wistar rats. The parameters were determined at 14 and 21 days after OJ. Two additional groups of animals were treated with anti-TNF-alpha antibodies or submitted to bile duct drainage at 14 days, and sacrificed 21 days after OJ. Cholestasis decreased glucose, and enhanced urea, creatinin, bilirubin and transaminases. Cholestasis increased the number of different inflammatory cells (T and B lymphocytes, and monocytes-macrophages) but reduced the expression of the corresponding cellular activation markers. This low responsiveness of the inflammatory cells was related to a decreased free radical production and phagocytic activity of cells. Anti-TNF-alpha and bile duct drainage reduced tissue injury, and prevented the reduction of the number and activity of T lymphocytes and phagocytic cells observed at the advanced stages of cholestasis. In conclusion, anti-TNF- alpha and bile duct drainage improved cell immunodeficiency, and reduced liver injury, cholestasis and renal insufficiency in experimental OJ.

Objective: Surgery in patients with malignant obstructive jaundice is associated with increased risks for postoperative septic complications. The aim of this study was to investigate the inflammatory and the local cellular immune response in patients accepted for surgery because of tumours in the hepatic-pancreatic-biliary (HPB) tract., Material and Methods: Patients with obstructive jaundice (group HPB(+)) were compared with those without (HPB(-)). Patients undergoing surgery for benign abdominal disorders served as controls. Obstructive jaundice was present in 18 out of 33 HPB patients. Preoperatively, blood was analysed for bacteria, endotoxins and cytokines (TNF-alpha, IL-6 and IL-10). At operation, mesenteric lymph nodes (MLNs) were excised for bacterial cultures using standard microbiological techniques, and immunohistochemistry, using antibodies CD4 and CD8 (mainly staining T lymphocytes), CD68 (macrophages), and anti-caspase-3 (to determine the rate of apoptosis)., Results: Bacterial translocation was not demonstrated in any of the patients. Increased preoperative concentrations of endotoxins were found in group HPB(+). The number of macrophages and the rate of apoptosis in MLNs were increased in jaundiced patients, while the number of T lymphocytes was decreased., Conclusions: Malignant obstructive jaundice causes increased blood concentrations of endotoxins and cytokines, an increased number of macrophages in MLNs, a higher rate of apoptosis in MLNs, but a decreased number of T lymphocytes in MLNs. The lymphocyte depletion is probably due to the increased rate of apoptosis, and might reduce the ability of jaundiced patients to eradicate infection.

Background: Transforming growth factor (TGF) beta is a potent inhibitor of hepatocyte DNA synthesis and liver regeneration. TGF-beta(1) expression progressively increases in obstructive jaundice. We investigated the effect of TGF-beta(1) blockage on liver regeneration in rats induced with obstructive jaundice., Materials and Methods: Male Wistar-albino rats were divided into three groups: sham, control, and study groups. In the study and control groups, the common bile duct was ligated and divided, and 7 days later a partial hepatectomy was performed. In the study group, anti-TGF-beta(1) monoclonal antibody (10-microg single dose) was administered immediately after the 70% hepatectomy. In the control group, those rats in which obstructive jaundice was induced received normal saline after the 70% hepatectomy, and nonjaundiced rats received anti-TGF-beta(1) monoclonal antibody after the 70% hepatectomy. Rats were sacrificed after 48 or 72 h. Relative liver weight, AST, ALT, total and conjugated bilirubin, and TGF-beta(1) levels were measured. The mitotic index and proliferating cell nuclear antigen (PCNA) labeling index were evaluated as histopathologic parameters., Results: At 72 h, the TGF-beta(1) level in the study group was similar to that in the sham group, whereas TGF-beta(1) in the study group was significantly lower than that of the jaundiced control group at 48 or 72 h (P < 0.001). The relative liver weight, mitotic index, and PCNA labeling index were significantly higher in the study group than in the jaundiced control group at 48 and 72 h (P < 0.001). The AST, ALT, and TGF-beta(1) levels were significantly higher in the jaundiced control group compared to the study group after 48 and 72 h, whereas these values were significantly lower in the nonjaundiced control group (P < 0.001)., Conclusions: In obstructive jaundiced rats, TGF-beta(1) blockage with anti-TGF-beta(1) monoclonal antibody after liver resection improved liver regeneration both morphologically and functionally.

To investigate the association between chronic cholestatic jaundice, systemic immunity, and various infectious complications in patients with biliary atresia (BA), we performed a survey of the systemic immune function in 30 children with BA. Patients were divided into a jaundice group (total serum bilirubin > or = 2 mg/dL for >6 mo) and control group (total serum bilirubin <2 mg/dL for >6 mo) with comparable age. Patients were tested for serum immunoglobulin and complement levels, mitogen response, interleukin (IL)-4, IL-5, and interferon-gamma production after phytohemagglutinin (PHA) stimulation, blood cell and lymphocyte subpopulation counts, phagocytic function, and leukocyte adhesion complex. They were then followed prospectively for 6 mo, and severe infectious complications requiring hospitalization were recorded. Compared with jaundice-free patients, T-lymphocyte proliferation function, determined by PHA mitogen test was significantly lower (p = 0.02) in BA patients with chronic cholestatic jaundice after a Kasai operation. During the study period, patients with chronic cholestatic jaundice had a higher risk of severe infectious complications than their jaundice-free counterparts (risk ratio = 5.87; p = 0.001). In conclusion, BA patients with chronic cholestatic jaundice are associated with impairment of T-lymphocyte proliferation and increased incidence of severe infectious complications.

Obstructive jaundice is associated with immunologic derangements and hepatic inflammation and fibrosis. Because dendritic cells (DCs) play a major role in immune regulation, we hypothesized that the immunosuppression associated with jaundice may result from the functional impairment of liver DCs. We found that bile duct ligation (BDL) in mice expanded the myeloid subtype of liver DCs from 20 to 80% of total DCs and increased their absolute number by >15-fold. Liver myeloid DCs following BDL, but not sham laparotomy, had increased Ag uptake in vivo, high IL-6 secretion in response to LPS, and enhanced ability to activate T cells. The effects of BDL were specific to liver DCs, as spleen DCs were not affected. Expansion of liver myeloid DCs depended on Gr-1(+) cells, and we implicated monocyte chemotactic protein-1 as a potential mediator. Thus, obstructive jaundice selectively expands liver myeloid DCs that are highly functional and unlikely to be involved with impaired host immune responses.

Background: Sclerosing pancreatitis is an autoimmune condition characterized by periductal lymphocytic infiltration on histology, and elevated serum auto-antibodies and IgG4. Bile duct involvement is often associated with sclerosing pancreatitis but it is rarely the dominant feature., Case Report: We report a patient with dominant biliary stricture and obstructive jaundice associated with IgG4 negative autoimmune pancreatitis. Due to uncertainties regarding the preoperative diagnosis, the patient underwent bilio-enteric bypass with an intraoperative pancreatic and bile duct biopsy. Post operatively, due to disease recurrence, the patient was started on steroids with consequent remission of the disease., Conclusion: Sclerosing pancreatitis may sometimes present with biliary stricture due to bile duct involvement due to the inflammatory process. The condition is often recognized after surgical exploration for a suspected malignancy. Preoperative diagnosis permits treatment with steroids and endoscopic biliary decompression, and avoids unnecessary surgery.

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.

Objectives: Autoimmune pancreatitis (AIP) is a unique clinical entity that has been recently proposed, and it is frequently associated with bile duct stricture. The aim of this study was to investigate the pathophysiology of the biliary tract involvement in patients with AIP., Methods: We evaluated the clinicopathologic findings in 16 patients with AIP. Surgical resection was performed in 7 of the patients because of suspicion of a pancreatic tumor; 8 of the other patients were treated with oral prednisolone (PSL) therapy, and the remaining patient was observed clinically and not treated. The pancreas, bile duct, and gallbladder in the surgical cases were examined histologically and immunohistochemically. We also assessed the clinical manifestations and diagnostic imaging findings before and after oral PSL therapy in the 8 patients treated with PSL., Results: Stricture of the extrahepatic bile duct was detected in 88% (14/16) of the patients. Thickening of the bile duct wall was detected in 94% (15/16), and thickening of the gallbladder wall was observed in 56% (9/16). Histologically, the bile duct and gallbladder wall were characterized by diffuse lymphoplasmacytic infiltration and marked interstitial fibrosis. Immunohistochemically, the diffusely infiltrating cells consisted of predominantly CD8- or CD4-positive T lymphocytes and IgG4-positive plasma cells. These findings were the same as in the inflammatory process that was observed in the pancreas. After oral PSL therapy, the pancreatic enlargement and irregular narrowing of the main pancreatic duct improved to almost their normal size in all 8 patients; however, stricture of the extrahepatic bile duct persisted in 4 of the patients (57%, 4/7) in whom it was detected before PSL therapy., Conclusions: Based on the pathophysiologic and histologic findings and the response to PSL therapy, the biliary involvement in AIP developed by the same mechanism as the pancreatitis. CD8- and CD4-positive lymphocytes and IgG4-positive plasma cells may play an important role in the pathogenesis of AIP.

Background: Although the effect of preoperative biliary drainage in patients with obstructive jaundice is controversial, bacterial or endotoxin translocation is one of the main postoperative problem in jaundiced patients. Failure in gut barrier functions causes bacterial translocation; homing and distribution of T lymphocytes in the intestinal lamina propria are important for gut mucosal immune defense. This study was performed to examine whether bile regulates the numbers of T lymphocyte subsets or the expression of mucosal addressin cell adhesion molecule-1 (MAdCAM-1) in experimental jaundice in rats with and without external and internal biliary drainage., Methods: Four groups of Wistar rats were used: those that received a sham operation (SHAM), common bile duct ligation (CBDL), CBDL followed by external drainage (ED), and CBDL followed by internal drainage (ID). Numbers of CD4(+) and CD8(+) T lymphocytes and MAdCAM-1-positive cells in the lamina propria were counted immunohistochemically in the specimens of jejunum and ileum of each group. Bacterial translocation was examined by culturing from the mesenteric lymph node complex isolated from rats in each group., Results: A significant decrease in numbers of CD4(+) and CD8(+) T lymphocytes and MAdCAM-1-positive cells in the lamina propria was seen in obstructive jaundice, although numbers of peripheral blood lymphocytes increased in comparison with the sham-operated control. The numbers of CD4(+) and CD8(+) T lymphocytes and MAdCAM-1 expression in the lamina propria did not recover to a normal level after external drainage, but did so after internal drainage. Frequencies of bacterial translocation were high in the CBDL and ED group. In contrast, bacterial translocation was not present in any animals in the SHAM group and was at a low percentage in the ID group., Conclusions: Changes in the number of T lymphocytes and MAdCAM-1 expression are associated with the presence of bile in the gastrointestinal tract and are inversely correlated with the frequency of bacterial translocation induced by CBD ligation. MAdCAM-1 expression maintained by the presence of bile may regulate T-lymphocyte homing to the lamina propria in obstructive jaundice.

Purpose: Bacterial translocation leading to sepsis is increased by obstructive jaundice(OJ). Antithrombin III (ATIII) mediates the promotion of prostaglandin release, an inhibitor of leucocyte activation and downregulator of many proinflammatory cytokines. We investigated the effect of ATIII on histopatology and villus morphology of small intestine., Material and Methods: We designed an experimental study with 40 rats who were divided into four groups. The first one (control, n = 10) received saline, the second (n = 10) included normal rats who received ATIII, the third group (n = 10) was rats with OJ (ligation of common bile duct), and the fourth group included OJ rats receiving AT-III. AT-III (100 UI/kg intraperitoneally) was started at the third day following bile duct ligation and repeated for 5 days. At the 8 day, rats were scarified and ileum was analysed. Histopathological assessments were performed, using a grading scheme ranging from 0 to 10 (Chui et al)., Results: Median histological score was found to be 2 in group 1, 1.71 in group 2, 5.43 in group 3 and 2.71 in group 4. The difference between group 3 and 4 was statistically significant. Mucosal thicknesses and villus lengths were found significantly lower in OJ group. Mucosal thicknesses and villus lengths were significantly preserved in jaundiced + AT-III group., Conclusion: ATIII demonstrated a salutary effect on the histopathological changes caused by the OJ and prevented the adverse effects on histopathological and morphological parameters in ileal mucosa.

The aim of this study was to investigate the relationship between the obstructive jaundice-induced cellular immune suppression and endotoxin challenge with respect to the levels of tumor necrosis factor (TNF), interleukin-10 (IL-10), and interleukin-2 (IL-2). Rats underwent either bile duct ligation or sham operation. At 21 days, all rats were challenged either with lipopolysaccharide (LPS) or saline. In the sham-operated group LPS injection significantly increased TNF levels at 90 min. The common bile duct ligated group showed a significant increase in TNF levels compared with all other groups, including the sham-operated, LPS-injected group, at 90 min. At 180 min following LPS challenge, TNF levels decreased, and there was no difference between any of the LPS-challenged groups at 180 min and any of the saline groups at either 90 or 180 min. In the sham-operated group, LPS injection significantly increased IL-10 levels at both 90 and 180 min. In the bile duct ligated group, LPS injection significantly increased IL-10 levels compared with saline injection at both 90 and 180 min. On the other hand, bile duct ligated animals had significantly less increase in IL-10 levels following LPS challenge at 90 min but not at 180 min. In common bile duct ligated rats, LPS challenge induced a significantly greater increase in IL-2 levels compared with all other groups. In conclusion, in the presence of obstructive jaundice, endotoxemia primes a more vigorous inflammatory response despite cellular immune depression.

Recently, T cells were classified into two categories: intrathymic T cells (ITCs; thymus-derived T cells) and extrathymic T cells (ETCs). ETC, localized in the liver and intestinal intraepithelium (IE), play an important immunologic role in the suppressed condition of T-cell development in the thymus. Given the fact that complications of surgery in patients with obstructive jaundice are often related to immunosuppression in the gut-liver circulation, we attempted to investigate the changes in the proportion of ETCs in mice with obstructive jaundice. Three mice models were prepared ( n = 10 per group): sham group with simple laparotomy; ligation group with common bile duct ligation; deoxycholic acid (DCA) group with an oral intake of DCA as a model of the presence of bile salts in the gut lumen. In each model, total mononuclear cells (MNCs), ITCs in the thymus, and ETCs in the liver and IE were counted using monoclonal antibodies in conjunction with a two-color immunofluorescence test by flow cytometry. In the ligation group the number of MNCs was reduced in the thymus and IE, and only those in the IE recovered after oral intake of DCA. A decrease of ITCs in the thymus and the increase in ETCs in the liver and IE occurred simultaneously during the early phase of biliary obstruction. At day 7 after biliary obstruction, ETCs in the livers of the DCA and ligation groups decreased to nearly the level in the sham group. However, on day 7 the ETCs in the IE remained significantly higher in the DCA group than in the ligation group. These results suggested that ETCs can act in place of ITCs at an early phase of obstructive jaundice, and the presence of bile in the gut lumen may be associated with the consumption of ETCs in the IE, a reaction that may bring about improved immunoreactivity.

Background/purpose: The effects of preoperative biliary drainage for obstructive jaundiced patients are controversial. Although experimental studies have proven the benefit of internal biliary drainage (ID) over external biliary drainage (ED), ID has several clinical problems, such as clogging or tube replacement. The aim of this study was to determine whether there were any differences in T-cell function, liver function, and histology, between rats in ID and ED groups in short-term experiments., Methods: Following bile duct ligation (BDL) for 14 days, rats in the ED and ID groups had 7 days of ED and 7 days of ID, respectively. Normal rats were used as negative controls (control group). For positive controls, we used a group with BDL and no drainage (BDL group). Serum bilirubin, aspartate aminotransferase (AST), alanine aminotransferase (ALT), and alkaline phosphatase (ALP) were measured, splenic T-cell proliferation was assayed to check cellular immunity, and liver histology was examined., Results: Recovery of bilirubin and ALT was similar in the ED and ID groups. Recovery of AST was worse in the ID group than in the ED group, but the difference was not statistically significant. Levels of ALP in the BDL and ID groups were significantly higher than those in the control and ED groups. Rats in the BDL group showed a significant decrease in T-cell function compared to the control group. The ED group showed better recovery of T-cell function than the ID group in the 7 days after relief of obstructive jaundice. The livers in the ID group demonstrated histologically moderate interface hepatitis with periportal inflammation and lymphocyte infiltration, which strongly suggested incomplete tube obstruction, but those in the ED group showed minimal change., Conclusions: ED is superior to ID concerning the recovery of cellular immunity and liver inflammation in the short-term after relief from biliary obstruction in this model. As the patency of the tube is well maintained in ED compared to ID, patency of the tube is essential to obtain good recovery of cellular immunity, irrespective of the drainage method., (Copyright 2004 Springer-Verlag)

Objects: To explore the roles of the protein kinase C (PKC) signal pathway in immunologic evaluation of patients with obstructive jaundice., Methods: PKC from cytosolic and membrane fractions of peripheral blood lymphocytes (PBL) was isolated and purified, then its activities were determined by radioactive isotope gamma-32P-ATP-catalyzing assay., Results: Total PKC activities in PBL in patients with obstructive jaundice were significantly (r = 0.64, P < 0.01) increased as compared to those in normal subjects. Moreover, the membrane PKC activities and their percentages of the total PKC activities were higher in the patients with obstructive jaundice than in normal subjects (r = 0.63, P < 0.05). The total PKC activities in PBL were significantly correlated with the levels of soluble IL-2 receptor (sIL-2R) (r = 0.67, P < 0.01) and the degree of jaundice (T-BIL) (r = 0.58, P < 0.01) in serum., Conclusions: The activities of the PKC signal pathway is related to the degree of T-BIL. PKC may be implicated in the activation of T-lymphocytes in patients with obstructive jaundice. It is suggested that the role of the PKC signal pathway may be important in the immune regulation and the assessment of pathosis in patients with obstructive jaundice.