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IntroductionIn pancreatic cancer, preoperative biliary drainage (PBD) increases complications compared with surgery without PBD, demonstrated by a recent randomised controlled trial (RCT). This outcome might be related to the plastic endoprosthesis used. Metal stents may reduce the PBD-related complications risk.MethodsA prospective multicentre cohort study was performed including patients with obstructive jaundice due to pancreatic cancer, scheduled to undergo PBD before surgery. This cohort was added to the earlier RCT (ISRCTN31939699). The RCT protocol was adhered to, except PBD was performed with a fully covered self-expandable metal stent (FCSEMS). This FCSEMS cohort was compared with the RCT’s plastic stent cohort. PBD-related complications were the primary outcome. Three-group comparison of overall complications including early surgery patients was performed.Results53 patients underwent PBD with FCSEMS compared with 102 patients treated with plastic stents. Patients’ characteristics did not differ. PBD-related complication rates were 24% in the FCSEMS group vs 46% in the plastic stent group (relative risk of plastic stent use 1.9, 95% CI 1.1 to 3.2, p=0.011). Stent-related complications (occlusion and exchange) were 6% vs 31%. Surgical complications did not differ, 40% vs 47%. Overall complication rates for the FCSEMS, plastic stent and early surgery groups were 51% vs 74% vs 39%.ConclusionsFor PBD in pancreatic cancer, FCSEMS yield a better outcome compared with plastic stents. Although early surgery without PBD remains the treatment of choice, FCSEMS should be preferred over plastic stents whenever PBD is indicated.Trial registration number:Dutch Trial Registry (NTR3142).

Preoperative biliary drainage is often performed in patients with obstructive jaundice caused by cancer of the pancreatic head, but the benefit of the procedure is unclear. This randomized trial compared 4 to 6 weeks of preoperative biliary drainage, followed by surgery, with immediate surgery alone for cancer of the pancreatic head. The drainage procedure increased morbidity and did not decrease the rate of surgical complications. This randomized trial compared 4 to 6 weeks of preoperative biliary drainage, followed by surgery, with immediate surgery alone for cancer of the pancreatic head. The drainage procedure increased morbidity and did not decrease the rate of surgical complications. Obstructive jaundice is the most common symptom in patients with periampullary cancer (located near the ampulla of Vater) or cancer of the pancreatic head. For patients with a resectable tumor who have no radiologic evidence of metastasis, surgical resection is the only option for cure. 1 – 3 Since surgery in patients with jaundice is thought to increase the risk of postoperative complications, preoperative biliary drainage was introduced to improve the postoperative outcome. 4 In several experimental studies and retrospective case series, preoperative biliary drainage reduced morbidity and mortality after surgery. 4 – 7 However, two meta-analyses of randomized trials and a systematic review of . . .

To evaluate the utility and safety of a short-type double-balloon endoscope (DBE) in the treatment of biliary disease in patients with surgically altered gastrointestinal (GI) anatomy. This study was conducted as a multicenter, single-arm, prospective trial at five tertiary academic care centers and three community-based hospitals in Japan. Consecutive patients with biliary disease with altered GI anatomy were prospectively included in this study. A total of 311 patients underwent double-balloon endoscopic retrograde cholangiography (ERC). The success rate of reaching the target site, the primary end point, was 97.7% (95% confidence interval (CI): 95.4-99.1). The success rate of biliary cannulation and contrast injection of the targeted duct, the secondary end point, was 96.4% (95% CI: 93.6-98.2), and the therapeutic success rate was 97.9% (95% CI: 95.4-99.2). Adverse events occurred in 33 patients (10.6%, 95% CI: 7.1-14.0) and were managed conservatively in all patients with the exception of 1 in whom a perforation developed, requiring emergency surgery. ERC using a short-type DBE resulted in an excellent therapeutic success rate and a low rate of adverse events. This treatment can be a first-line treatment for biliary disease in patients with surgically altered GI anatomy.

Background It is well known that obstructive jaundice could affect the pharmacodynamics of some anesthetics, and the sensitivity of some anesthetics would increase among icteric patients. Remimazolam is a new ultra-short-acting intravenous benzodiazepine sedative/anesthetic, which is a high-selective and affinity ligand for the benzodiazepine site on the GABAA receptor. However, no study has reported the pharmacodynamics of remimazolam in patients with obstructive jaundice. We hypothesize that obstructive jaundice affects the pharmacodynamics of remimazolam, and the sensitivity of remimazolam increases among icteric patients. Methods/design The study will be performed as a prospective, controlled, multicenter trial. The study design is a comparison of remimazolam requirements to reach a bispectral index of 50 in patients with obstructive jaundice versus non-jaundiced patients with chronic cholecystitisor intrahepatic bile duct stones. Remimazolam was infused at 6 mg/kg/h until this endpoint was reached. Discussion Remimazolam could be suitable for anesthesia of patients with obstructive jaundice, because remimazolam is not biotransformed in the liver. Hyperbilirubinemia has been well-described to have toxic effects on the brain, which causes the increasing of sensitivity to some anesthetics, such as desflurane, isoflurane, and etomidate. Furthermore, remimazolam and etomidate have the same mechanism of action when exerting an anesthetic effect. We aim to demonstrate that obstructive jaundice affects the pharmacodynamics of remimazolam, and the dose of remimazolam when administered to patients with obstructive jaundice should be modified. Trial registration Chinese Clinical Trial Registry ChiCTR2100043585 . Registered on 23 February 2021

Objectives Patients with obstruction jaundice are at a high risk of hypotension and need high volume of fluids and a high dose of catecholamine to maintain organ perfusion during operation procedure. All these likely contribute to high perioperative morbidity and mortality. The aim of the study is to evaluate the effects of methylene blue on the hemodynamics in patients undergoing surgeries associated with obstructive jaundice. Design A prospective, randomized, and controlled clinical study. Setting The enrolled patients randomly received 2 mg/kg of methylene blue in saline or saline (50 ml) before anesthesia induction. The primary outcome was the frequency and dose of noradrenaline administration to maintain mean arterial blood pressure over 65 mmHg or > 80% of baseline, and systemic vascular resistance (SVR) over 800 dyne/s/cm 5 during operation. The secondary outcomes were liver and kidney functions, and ICU stay. Patients Seventy patients were enrolled in the study and randomly assigned to receive either methylene blue or control ( n  = 35/group). Results Fewer patients received noradrenaline in the methylene blue group when compared with the control group (13/35 vs 23/35, P  = 0.017), and the noradrenaline dose administrated during operation was reduced in the methylene blue group when compared with the control group (0.32 ± 0.57 mg vs 1.787 ± 3.51 mg, P  = 0.018). The blood level of creatinine, glutamic oxalacetic transaminase, and glutamic–pyruvic transaminase after the operation was reduced in the methylene blue group when compared with the control group. Conclusions Prophylactic administration of methylene blue before operation associated with obstructive jaundice improves hemodynamic stability and short-term prognosis. Question Methylene blue use prevented refractory hypotension during cardiac surgery, sepsis, or anaphylactic shock. It is still unknown that methylene blue on the vascular hypo-tone associated with obstructive jaundice. Findings Prophylactic administration with methylene blue improved peri-operative hemodynamic stability, and hepatic and kidney function on the patients with obstructive jaundice. Meanings Methylene blue is a promising and recommended drug for the patients undergoing the surgeries of relief obstructive jaundice during peri-operation management.

Dexmedetomidine, a highly selective central α2-agonist, undergoes mainly biotransformation in the liver. The pharmacokinetics of dexmedetomidine were significantly affected by hepatic insufficiency. The clearance of dexmedetomidine in patients with severe hepatic failure decreased by 50% compared with controls. We tested the hypothesis that the pharmacokinetics of dexmedetomidine would be affected by obstructive jaundice. The prospective registration number of clinical trial is ChiCTR-IPR-15007572. 18 patients with obstructive jaundice and 12 non-jaundiced patient controls received dexmedetomidine, 1 μg/kg, over 10 min. Arterial blood samples were drawn before, during, and up to 5 h after the infusion. Plasma dexmedetomidine concentrations were determined by 1290 infinity high performance liquid chromatography coupled with 6470 tandem mass spectrometry. The relevant pharmacokinetic parameters were calculated by non-compartmental analysis using Phoenix WinNonlin 7.0. Plasma clearance of dexmedetomidine was decreased by 33.3% in the obstructive jaundice group as compared with the control group (0.0068±0.0017 vs. 0.0102±0.0033 L/kg/min; P = 0.002). Volume of distribution was decreased by 29.2% in the obstructive jaundice group as compared with the control group (1.43±0.58 vs. 2.02±0.84 L/kg; P = 0.041). This study demonstrates that the clearance and distribution volume of dexmedetomidine were decreased in patients with obstructive jaundice. It may be advisable to adjust the dose of dexmedetomidine in those patients.

Background Jaundice is a common symptom of inherited or acquired liver diseases or a manifestation of diseases involving red blood cell metabolism. Recent progress has elucidated the molecular mechanisms of bile metabolism, hepatocellular transport, bile ductular development, intestinal bile salt reabsorption, and the regulation of bile acids homeostasis. Main body The major genetic diseases causing jaundice involve disturbances of bile flow. The insufficiency of bile salts in the intestines leads to fat malabsorption and fat-soluble vitamin deficiencies. Accumulation of excessive bile acids and aberrant metabolites results in hepatocellular injury and biliary cirrhosis. Progressive familial intrahepatic cholestasis (PFIC) is the prototype of genetic liver diseases manifesting jaundice in early childhood, progressive liver fibrosis/cirrhosis, and failure to thrive. The first three types of PFICs identified (PFIC1, PFIC2, and PFIC3) represent defects in FIC1 ( ATP8B1 ), BSEP ( ABCB11 ), or MDR3 ( ABCB4 ). In the last 5 years, new genetic disorders, such as TJP2, FXR, and MYO5B defects, have been demonstrated to cause a similar PFIC phenotype. Inborn errors of bile acid metabolism also cause progressive cholestatic liver injuries. Prompt differential diagnosis is important because oral primary bile acid replacement may effectively reverse liver failure and restore liver functions. DCDC2 is a newly identified genetic disorder causing neonatal sclerosing cholangitis. Other cholestatic genetic disorders may have extra-hepatic manifestations, such as developmental disorders causing ductal plate malformation (Alagille syndrome, polycystic liver/kidney diseases), mitochondrial hepatopathy, and endocrine or chromosomal disorders. The diagnosis of genetic liver diseases has evolved from direct sequencing of a single gene to panel-based next generation sequencing. Whole exome sequencing and whole genome sequencing have been actively investigated in research and clinical studies. Current treatment modalities include medical treatment (ursodeoxycholic acid, cholic acid or chenodeoxycholic acid), surgery (partial biliary diversion and liver transplantation), symptomatic treatment for pruritus, and nutritional therapy. New drug development based on gene-specific treatments, such as apical sodium-dependent bile acid transporter (ASBT) inhibitor, for BSEP defects are underway. Short conclusion Understanding the complex pathways of jaundice and cholestasis not only enhance insights into liver pathophysiology but also elucidate many causes of genetic liver diseases and promote the development of novel treatments.

Background and Aims Amoxicillin–clavulanate (AC) is the most frequent cause of idiosyncratic drug-induced injury (DILI) in the US DILI Network (DILIN) registry. Here, we examined a large cohort of AC-DILI cases and compared features of AC-DILI to those of other drugs. Methods Subjects with suspected DILI were enrolled prospectively, and cases were adjudicated as previously described. Clinical variables and outcomes of patients with AC-DILI were compared to the overall DILIN cohort and to DILI caused by other antimicrobials. Results One hundred and seventeen subjects with AC-DILI were identified from the cohort ( n  = 1038) representing 11 % of all cases and 24 % of those due to antimicrobial agents ( n  = 479). Those with AC-DILI were older (60 vs. 48 years, P  < 0.001). AC-DILI was more frequent in men than women (62 vs. 39 %) compared to the overall cohort (40 vs. 60 %, P  < 0.001). The mean time to symptom onset was 31 days. The Tb, ALT, and ALP were 7 mg/dL, 478, and 325 U/L at onset. Nearly all liver biopsies showed prominent cholestatic features. Resolution of AC-DILI, defined by return of Tb to <2.5 mg/dL, occurred on average 55 days after the peak value. Three female subjects required liver transplantation, and none died due to DILI. Conclusion AC-DILI causes a moderately severe, mixed hepatocellular–cholestatic injury, particularly in older men, unlike DILI in general, which predominates in women. Although often protracted, eventual apparent recovery is typical, particularly for men and usually in women, but three women required liver transplantation.

The main cause of distal biliary malignant obstructive jaundice (DBMOJ) is the stricture of the extrahepatic biliary tract by malignant tumors, including pancreatic head and uncinate process cancer, low-grade cholangiocarcinoma, duodenal cancer, papillary duodenal cancer and other malignant tumors. The most effective treatment is radical pancreaticoduodenectomy. However, preoperative obstructive jaundice can affect the patient’s liver function and blood coagulation function, increase local inflammation and oedema, and make surgery more difficult. Patients with severe obstructive jaundice require preoperative biliary drainage, which can be achieved by various methods, including ultrasound endoscopic biliary drainage (EUS-EBD) and endoscopic retrograde biliary drainage (ERBD). The latter is mainly divided into endoscopic nasobiliary drainage and endoscopic biliary stent. Some patients underwent percutaneous transhepatic biliary drainage (PTBD) when ERBD and EUS-EBD failed. In this study, we aimed to identify PTBD in DBMOJ and to further investigate the role of the puncture pathway in DBMOJ. The relationship between PTBD and bile duct internal diameter was confirmed by analysing and collating clinical data. In this study, DBMOJ was grouped according to bile duct internal diameter and liver function was used as an indicator to examine the improvement in liver function with PTBD in patients undergoing DBMOJ. Analysis of puncture complications showed that PTBD puncture was safe. DBMOJ with different bile duct internal diameters had different rates of liver function improvement after PTBD. The right-side approaches had significantly lower alanine aminotransferase (ALT) and alanine transaminase (AST) than the left-side approaches. This study showed that PTBD for DBMOJ is associated with a low complication rate and good reduction of jaundice. Liver function recovery was faster in patients with DBMOJ treated with PTBD in the right-sided approach compared with the left-sided approach. PTBD is an effective tool to be used in patients who have failed ERBD and EUS-EBD.