Review article: Asia-Pacific consensus recommendations on endoscopic tissue acquisition for biliary strictures.

BACKGROUND: Pre-operative tissue diagnosis for suspected malignant biliary strictures remains challenging. AIM: To develop evidence-based consensus statements on endoscopic tissue acquisition for biliary strictures. METHODS: The initial draft of statements was prepared following a systematic literature review. A committee of 20 experts from Asia-Pacific region then reviewed, discussed, and modified the statements. Two rounds of independent voting were conducted to reach a final version. Consensus was considered to be achieved when 80% or more of voting members voted "agree completely" or "agree with some reservation." RESULTS: Eleven statements achieved consensus. The choice of tissue sampling modalities for biliary strictures depends on the clinical setting, the location of lesion, and availability of expertise. Detailed radiological and endoscopic evaluation is useful to guide the selection of appropriate tissue acquisition technique. Standard intraductal biliary brushing and/or forceps biopsy is the first option when endoscopic biliary drainage is required with an overall (range) sensitivity and specificity of 45% (26%-72%) and 99% (98%-100%), and 48% (15%-100%) and 99% (97%-100%), respectively, in diagnosing malignant biliary strictures. Probe-based confocal laser endomicroscopy and fluorescence in situ hybridisation using 4 fluorescent-labelled probes targeting chromosomes 3, 7, 17 and 9p21 locus may be added to improve the diagnostic yield. Cholangioscopy-guided biopsy and EUS-guided tissue acquisition can be considered after prior negative conventional tissue sampling with an overall (range) sensitivity and specificity of 60% (38%-88%) and 98% (83%-100%), and 80% (46%-100%) and 97% (92%-100%), respectively, in diagnosing malignant biliary strictures. CONCLUSION: These consensus statements provide evidence-based recommendations for endoscopic tissue acquisition of biliary strictures.

Ledipasvir and sofosbuvir for treatment of post- renal transplant hepatitis C infection: A case report with review of literature.

Liver disease due to hepatitis C infection in renal transplant recipients is difficult to treat and often associated with reduced patient survival. A 43-year-old male, a renal allograft recipient, presented at 6 years follow-up with significant weight loss over 3 months. He was detected to have new onset diabetes mellitus together with hepatitis C virus (HCV) infection (genotype 1). His HCV load remained high despite the change of immuno-suppression from tacrolimus to cyclosporine. A decision to treat with a new anti-viral combination of ledipasvir and sofosbuvir for 12 weeks was taken. Within 3 weeks, his raised serum transaminases levels normalized and viral load became undetectable. At the end of 16 weeks, he continues to do well with normal renal function, has sustained remission from hepatitis C infection and resolution of diabetes.

Endoscopic treatment of chronic pancreatitis: European Society of Gastrointestinal Endoscopy (ESGE) Clinical Guideline.

BACKGROUND AND AIMS: Clarification of the position of the European Society of Gastrointestinal Endoscopy (ESGE) regarding the interventional options available for treating patients with chronic pancreatitis. METHODS: Systematic literature search to answer explicit key questions with levels of evidence serving to determine recommendation grades. The ESGE funded development of the Guideline. SUMMARY OF SELECTED RECOMMENDATIONS: For treating painful uncomplicated chronic pancreatitis, the ESGE recommends extracorporeal shockwave lithotripsy/endoscopic retrograde cholangiopancreatography as the first-line interventional option. The clinical response should be evaluated at 6 - 8 weeks; if it appears unsatisfactory, the patient's case should be discussed again in a multidisciplinary team. Surgical options should be considered, in particular in patients with a predicted poor outcome following endoscopic therapy (Recommendation grade B). For treating chronic pancreatitis associated with radiopaque stones ≥ 5 mm that obstruct the main pancreatic duct, the ESGE recommends extracorporeal shockwave lithotripsy as a first step, combined or not with endoscopic extraction of stone fragments depending on the expertise of the center (Recommendation grade B). For treating chronic pancreatitis associated with a dominant stricture of the main pancreatic duct, the ESGE recommends inserting a single 10-Fr plastic stent, with stent exchange planned within 1 year (Recommendation grade C). In patients with ductal strictures persisting after 12 months of single plastic stenting, the ESGE recommends that available options (e. g., endoscopic placement of multiple pancreatic stents, surgery) be discussed in a multidisciplinary team (Recommendation grade D).For treating uncomplicated chronic pancreatic pseudocysts that are within endoscopic reach, the ESGE recommends endoscopic drainage as a first-line therapy (Recommendation grade A).For treating chronic pancreatitis-related biliary strictures, the choice between endoscopic and surgical therapy should rely on local expertise, patient co-morbidities and expected patient compliance with repeat endoscopic procedures (Recommendation grade D). If endoscopy is elected, the ESGE recommends temporary placement of multiple, side-by-side, plastic biliary stents (Recommendation grade A).

A new partially covered nitinol stent for palliative treatment of malignant bile duct obstruction: a multicenter single-arm prospective study.

BACKGROUND AND STUDY AIMS: Covered self-expanding metal stents (SEMSs) have proven effective for managing malignant bile duct strictures and may reduce risk of tumor ingrowth. A new nitinol partially covered biliary SEMS was prospectively evaluated. PATIENTS AND METHODS: 70 patients with inoperable extrahepatic biliary obstructions were enrolled in a prospective multicenter trial, and followed up to 6 months or death, whichever came first. Primary endpoint was adequate palliation defined as absence of recurrent biliary obstruction from partly covered SEMS placement to end of follow-up. RESULTS: Mean age of the patients was 69 years and 52 % were men. Pancreatic carcinoma was present in 68 %. One stent was placed in 67 patients, two patients received two, and in one patient a guide wire could not traverse the stricture. In 55 % of patients the SEMS was inserted de novo and in 45 % for exchange with a plastic stent. Technical success was 97 %. At 6 months, 62 % of patients were free of obstructive symptoms; compared with baseline the mean number of symptoms per patient was significantly reduced (3.1 at baseline, 0.6 at 6 months; P < 0.0001) and total bilirubin levels dropped by 73 %. There were four cases of recurrent biliary obstruction, due to stent migration (2), tumor overgrowth (1), and sludge formation (1). Device-related complications included cholecystitis (3), right upper quadrant pain (1), and moderate pancreatitis (1). No tumor ingrowth was reported. CONCLUSIONS: This new partially covered nitinol SEMS is easily inserted, and safe and effective in the palliation of biliary obstruction secondary to malignant bile duct strictures.

Clinical trial: a randomized trial comparing fluoroscopy guided percutaneous technique vs. endoscopic ultrasound guided technique of coeliac plexus block for treatment of pain in chronic pancreatitis.

BACKGROUND: Coeliac plexus block (CPB) is a management option for pain control in chronic pancreatitis. CPB is conventionally performed by percutaneous technique with fluoroscopic guidance (PCFG). Endoscopic ultrasound (EUS) is increasingly used for CPB as it offers a better visualization of the plexus. There are limited data comparing the two modalities. AIM: To compare the pain relief in chronic pancreatitis among patients undergoing CPB either by PCFG technique or by EUS guided technique. METHODS: Chronic pancreatitis patients with abdominal pain requiring daily analgesics for more than 4 weeks were included. Fifty six consecutive patients (41 males, 15 females) participated in the study. EUSG-CPB was performed in 27 and PCFG-CPB in 29 patients. In both the groups, 10 mL of Bupivacaine (0.25%) and 3 mL of Triamcinolone (40 mg) were given on both sides of the coeliac artery through separate punctures. RESULTS: Pre and post procedure pain scores were obtained using a 0-10 visual analogue scale. Improvement in pain scores was seen in 70% of subjects undergoing EUS-CPB and 30% in Percutaneous- block group (P = 0.044). CONCLUSIONS: EUS-guided coeliac block appears to be better than PCFG-CPB for controlling abdominal pain in patients with chronic pancreatitis.

A randomized controlled trial on use of propofol alone versus propofol with midazolam, ketamine, and pentazocine "sedato-analgesic cocktail" for sedation during ERCP.

BACKGROUND AND AIMS: Endoscopic retrograde cholangiopancreatography (ERCP) requires adequate patient sedation in order to carry out the procedure successfully. Propofol sedation is being increasingly used during ERCP. There are limited data to evaluate the efficacy of synergistic agents with propofol for sedation during ERCP. The aims of the current study were: (i) to compare patient sedation and tolerance during ERCP using either propofol alone or a "sedato-analgesic cocktail" for induction, along with propofol for maintenance, and (ii) to prospectively compare complications related to both sedation regimens. PATIENTS AND METHODS: This was a double-blind, randomized controlled trial with patients receiving either intravenous propofol alone (Group A) or a sedato-analgesic cocktail (midazolam, ketamine, and pentazocine plus propofol) (Group B) for induction; all patients received propofol for maintenance. Patient sedation and tolerance were assessed using 100-mm visual analog scales (VAS). RESULTS: A total of 199 patients undergoing ERCP were randomized (Group A, n = 104 vs. Group B, n = 95). Clinical characteristics were similar in both groups. Patient tolerance VAS scores were higher in Group B when assessed independently by both endoscopist ( P = 0.002) and anesthetist ( P = 0.001). The differences in scores occurred predominantly in younger patients. The mean propofol requirement was 192 mg in Group A and 131 mg in Group B; the mean difference was 61 mg (95%CI 40-82 mg). Patients reported equivalent levels of satisfaction with both sedation regimens. On multivariate analysis, "cocktail" use ( P = 0.013) and increasing age ( P = 0.027) significantly improved patient tolerance during ERCP. Caution during "cocktail" induction is required as transient oxygen desaturation occurs. CONCLUSION: During ERCP, propofol with a sedato-analgesic cocktail for induction results in improved patient tolerance compared with propofol alone, particularly in younger patients. Generalizations from this study to the Western world and to different cultural groups require further study.

Granulocyte macrophage colony stimulating factor (GM-CSF) induced sero-protection in end stage renal failure patients to hepatitis B in vaccine non-responders.

Hepatitis B (HB) virus infection is a major health problem in dialysis dependent end stage renal failure (ESRF) patients. The sero-conversion rate after recombinant HB vaccine in ESRF patients is poor. Adjuvants like Granulocyte Macrophage-Colony Stimulating Factor (GM-CSF) have been found to improve response rate to vaccines. This study was conducted to evaluate the efficacy of GM-CSF as an adjuvant to HB vaccine in ESRF patients who were non-responders to the usual three double dose vaccinations (primary non-responders). Fifty consecutive HBsAg negative and anti-HBs negative ESRF patients on hemodialysis over thirty months were prospectively included (Jan. 96-June 98). All received 40 microg of recombinant HB vaccine at 0, 1, 2 month interval. Anti-HBs titres were subsequently tested after four weeks of the third dose. There were 19 (38%) primary non-responders (antiHBs negative). Twelve (Group I) of primary non-responders were given an additional dose of HB vaccine with 300 microg (5-6 microg/kg) of GM-CSF (Leucomax) and the remaining seven (Group II) received only an additional dose of HB vaccine. Anti-HBs was determined by Abbott's ELISA kit, and titre above 10 mIU/mL was considered as protective. In Group I, sero-protective titres were obtained in 11 out of 12 (91.6%) patients, whereas in Group II none of the patients achieved sero-protection (p < 0.001). The sero-conversion rate improved from initial 62% (31/50) to overall 84% (42/150) after the use of GM-CSF. There were no adverse events noted with the use of GM-CSF. At one year, 24 out of 32 (75%) who were sero-protected earlier continued to remain sero-protected. This study indicates that GM-CSF is a potent HB vaccine adjuvant for sero-conversion in primary non-responders.

Falciparum malaria with acute liver failure.

INTRODUCTION: Falciparum malaria occasionally presents with encephalopathy, jaundice and fever mimicking fulminant hepatic failure. PATIENTS: We recently managed seven cases (mean age 34 years, range 20-45; all men) of acute falciparum malaria presenting with a short history [mean duration 8.1 (4-15) days] of fever, jaundice, altered sensorium and oliguria. Only one patient had splenomegaly. Investigations revealed jaundice (bilirubin 1.9-30.7 mg/dl), moderate to severe anaemia (Hb 4-8 gm/dl), increased liver enzymes (2-4 times normal) and azotaemia (serum creatinine 1.6-7.4 mg/dl). Coagulation parameters were deranged in 3 with clinical bleeding in two cases. One patient without a past history of diabetes had increased blood glucose values with ketonuria. HBsAg was negative in all cases. Patients received supportive therapy along with intravenous quinine. Peritoneal dialysis was done in one patient. Three patients showed rapid recovery and four succumbed to the disease. Post-mortem liver biopsy showed Kupffer cell hyperplasia, pigment deposition, foci of steatosis and necrosis along with submassive necrosis in one case. CONCLUSIONS: In areas endemic for malaria, awareness of this entity is a must. In a patient with jaundice and altered sensorium, disproportionate anaemia, azotaemia and only mild elevation of liver enzymes should help differentiate these patients from cases of fulminant hepatic failure. The diagnosis can be confirmed by peripheral blood examination. Early institution of specific therapy may be the only life saving measure in these patients.

A comparative study of three different test diets in change in plasma total cholesterol in young healthy individuals.

The effect of single dose of three different types of high cholesterol diet on plasma total cholesterol (PTC) in 24 young healthy subjects (male:female = 1:1) aged 15 to 35 years was studied. One group (n1 = 8) was given a butter and milk diet (300 mg cholesterol and 95 g fat). In the first postprandial hour PTC level increased significantly in all but one subject (mean +/- S.D., 4.96 +/- 0.57 m mol/l to 5.61 +/- 0.60 m mol/l, P < 0.005). Second group (n2 = 8) was given a single egg diet (300 mg cholesterol and 6 g fat). In the first hour the PTC level decreased significantly in all but 2 subjects (4.82 +/- 0.58 m mol/l to 4.42 +/- 0.63 m mol/l, P < 0.02). Third group subjects (n2(3) = 8) were given a test diet consisting of crystalline cholesterol with 200 ml milk (1020 mg cholesterol and 14 g fat). The PTC level increased insignificantly. In the first hour in all but 2 subjects (4.94 +/- 0.43 m mol/l to 5.35 +/- 0.88 m mol/l, P > 0.10). In the third postprandial hour the PTC values in all the 3 groups showed a tendency to return to fasting values. Therefore, we conclude that the effect of dietary cholesterol on PTC depends not only on the amount of cholesterol content in the diet, but on the type of diet (cholesterol vehicle) as such and probably also on the fat content of the diet.

Post heparin lipoprotein lipase activity in patients of ischaemic heart disease and in controls.

A single high fat meal diet (66 gm fat) was given to 30 healthy males and 20 male patients of ischaemic heart disease (IHD). Ten minutes prior to the 4th postprandial hour, 500 units of heparin--a lipoprotein lipase (LPL) activator--was given, and its effect seen on serum triglyceride (STG) levels observed. Besides higher fasting STG levels, the decline in 4 hour post-prandial STG level was significantly lower in patients of IHD. One explanation for higher fasting STG values and prolonged postprandial lipaemia in these subjects could be deficient LPL activity.