Routine preoperative biliary drainage in patients undergoing surgery for cancer of the pancreatic head increases the rate of complications. (Current Controlled Trials number, ISRCTN31939699.)

Fibroblast growth factor 19 (FGF19) is an endocrine factor produced by the small intestine in response to uptake of luminal bile salts. In the liver, FGF19 binds to FGF receptor-4, resulting in down-regulation of cytochrome P (CYP) 7A1 and reduced bile salt synthesis. Down-regulation of CYP7A1 under cholestatic conditions has been attributed to bile salt-mediated induction of the transcriptional repressor short heterodimer partner (SHP), because the interrupted enterohepatic cycle of bile salts is thought to abrogate intestinal FGF19 production and thus result in lowering of plasma FGF19 levels. Unexpectedly, we observed marked elevation of plasma FGF19 in patients with extrahepatic cholestasis caused by a pancreatic tumor (2.3 ؎ 2.3 in cholestatic versus 0.40 ؎ 0.25 ng/mL and 0.29 ؎ 0.12 ng/mL in postcholestatic patients who received preoperative drainage by biliary stenting, P ‫؍‬ 0.004, and noncholestatic control patients, P ‫؍‬ 0.04, respectively). Although FGF19 messenger RNA (mRNA) is virtually absent in normal liver, FGF19 mRNA was strongly increased (31-fold to 374-fold, P < 0.001) in the liver of cholestatic patients in comparison with drained and control patients. In the absence of changes in SHP mRNA, CYP7A1 mRNA was strongly reduced (7.2-fold to 24-fold, P < 0. B ecause they are potent detergents, synthesis of bile salts is subject to rigorous regulation. 1,2 The principal target for control of bile salt synthesis is the cytochrome P (CYP) 7A1 gene, which encodes the ratedetermining enzyme in the dominant biosynthetic pathway. Regulation of CYP7A1 occurs primarily at the transcriptional level and involves several nuclear hormone receptors. Among these ligand-activated transcription factors, the bile salt receptor FXR (farnesoid-X receptor) plays a key role in bile salt-mediated repression of CYP7A1. 2-4 Activation of hepatic FXR induces expression of short heterodimer partner (SHP), a transcriptional repressor that diminishes the transactivation potential of several transcription factors required for efficient CYP7A1 expression. [3][4][5] Activation of intestinal FXR by reabsorbed bile salts induces expression and portal release of FGF19 (fibroblast growth factor 19, termed Fgf15 in rodents). 6,7 Binding of FGF19/ Fgf15 to the cell surface receptor FGFR4 results in activation of mitogen-activated protein kinase pathways and downregulation of CYP7A1. 7,8 Studies in mice with intestine-specific or liver-specific disruption of the Fxr gene revealed that administration of a synthetic FXR agonist failed to repress Cyp7a1 in animals deficient in intestinal Fxr. 9 This study thus implied an important role for intestinal Fgf15 in regulation of bile salt synthesis.

Introduction Controversy exists over the preferred technique of preoperative biliary drainage (PBD) in patients with hilar cholangiocarcinoma (HCCA) requiring major liver resection. The current study compared outcomes of endoscopic biliary drainage (EBD) and percutaneous transhepatic biliary drainage (PTBD) in patients with resectable HCCA. Methods One hundred fifteen consecutive patients were explored for HCCA between 2001 and July 2008 and assigned by initial PBD procedure to either EBD or PTBD. Results Of these patients, 101 (88%) underwent PBD; 90 patients underwent EBD as primary procedure, and 11 PTBD. The technical success rate of initial drainage was 81% in the EBD versus 100% in the PTBD group (P=0.20). Stent dislocation was similar in the EBD and PTBD groups (23% vs. 20%, P=0.70). Infectious complications were significantly more common in the endoscopic group (48% vs. 9%, P<0.05). Patients in the EBD group underwent more drainage procedures (2.8 vs. 1.4, P<0.01) and had a significantly longer drainage period until laparotomy (mean 15 weeks vs. 11 weeks in the PTBD group; P<0.05). In 30 patients, EBD was converted to PTBD due to failure of the endoscopic approach. Conclusions Preoperative percutaneous drainage could outperform endoscopic stent placement in patients with resectable HCCA, showing fewer infectious complications, using less procedures.

Dutch Trial Registry (NTR3142).

The actuarial 5-year overall survival rate following pancreatic surgery for RCC metastases was 72.6 per cent, as determined by pooled analysis from published series. Extrapancreatic disease was an independent risk factor for recurrence, but had no significant impact on overall survival.

Rationale Preoperative biliary drainage (PBD) has been introduced to improve outcome after surgery in patients suffering from obstructive jaundice due to a potentially resectable proximal or distal bile duct/pancreatic head lesion. In experimental models, PBD is almost exclusively associated with beneficial results: improved liver function and nutritional status; reduction of systemic endotoxemia; cytokine release; and, as a result, an improved immune response. Mortality was significantly reduced in these animal models. Human studies show conflicting results. Findings For distal obstruction, currently the "best-evidence" available clearly shows that routine PBD does not yield the appreciated improvement in postoperative morbidity and mortality in patients undergoing resection. Moreover, PBD harbors its own complications. However, most of the available data are outdated or suffer from methodological deficits. Conclusion The highest level of evidence for PBD to be performed in proximal obstruction, as well as over the preferred mode, is lacking but, nevertheless, assimilated in the treatment algorithm for many centers. Logistics and waiting lists, although sometimes inevitable, could be factors that might influence the decision to opt for PBD, as well as an extended diagnostic workup with laparoscopy (on indication) or scheduled preoperative chemotherapy.

In patients with pancreatic head cancer, the delay in surgery associated with PBD does not impair or benefit survival rate.

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