Klaske A. C. Booij

The human gallbladder secretes fibroblast growth factor 19 into bile: Towards defining the role of fibroblast growth factor 19 in the enterobiliary tract

Fibroblast growth factor 19 (FGF19) plays a crucial role in the negative feedback regulation of bile salt synthesis. In the postprandial state, activation of ileal farnesoid X receptor (FXR) by bile salts results in transcriptional induction of FGF19 and elevation of circulating FGF19 levels. An intestinal‐liver axis of FGF19 signaling results in down‐regulation of bile salt synthesis. The aim of this study was to explore a broader signaling activity of FGF19 in organs engaged in the enterohepatic circulation of bile salts. For this aim, FGF19 expression and aspects of FGF19 signaling were studied in surgical specimens and in cell lines of hepatobiliary and intestinal origin. FGF19 messenger RNA was found to be abundantly expressed in the human gallbladder and in the common bile duct, with only minor expression observed in the ileum. Interestingly, human gallbladder bile contains high levels of FGF19 (21.9 ± 13.3 versus 0.22 ± 0.14 ng/mL in the systemic circulation). Gallbladder explants secrete 500 times more FGF19 than FXR agonist‐stimulated ileal explants. Factors required for FGF19 signaling (i.e., FGFR4 and βKlotho) are expressed in mucosal epithelial cells of the gallbladder and small intestine. FGF19 was found to activate signaling pathways in cell lines of cholangiocytic, enteroendocrine, and enterocytic origin. Conclusion: The combined findings raise the intriguing possibility that biliary FGF19 has a signaling function in the biliary tract that differs from its established signaling function in the portal circulation. Delineation of the target cells in bile‐exposed tissues and the affected cellular pathways, as well as a possible involvement in biliary tract disorders, require further studies. (HEPATOLOGY 2012)

Mesenteric cystic lymphangioma: a congenital and an acquired anomaly? Two cases and a review of the literature

Mesenteric cystic lymphangioma is an uncommon benign abdominal mass. Two cases of mesenteric cystic lymphangioma are presented, both in combination with malrotation and intermittent volvulus. Both mesenteric cystic lymphangiomas were located near the duodenojejunal junction, the usual area of torsion in case of a volvulus. These findings suggest that mesenteric cystic lymphangioma could have evolved as a consequence of chronic intermittent volvulus. We hypothesize that in patients with malrotation and volvulus, mesenteric cystic lymphangioma may be regarded as an acquired anomaly.

Evaluation of 28 years of surgical treatment of children and young adults with familial adenomatous polyposis.

BACKGROUND In this retrospective study, 28 years of surgical treatment of children and young adults with familial adenomatous polyposis (FAP) was analyzed. METHODS Forty-three patients were operated on before the age of 26 years. Endoscopic aspects, operative data, and complications were analyzed, and the resection specimens were reevaluated. Functional outcome was assessed by telephone questionnaire. RESULTS Primary ileorectal anastomosis (IRA) was performed in 34 patients with a mean age of 16 years (range, 7-25 years). Primary ileal-pouch anal anastomosis (IPAA) was performed in 9 patients at a mean age of 19 years (range, 15-24 years). Secondary excision of the rectum was performed in 7 patients. Overall, rectal carcinoma was present in 4 patients, at the age of 35, 36, 37, and 38 years. Two patients, aged 39 and 40 years, died because of invasive carcinoma with distant metastasis. The functional outcome and postoperative complications after both procedures were similar to those described in literature for children with FAP. Most patients did not experience alterations in lifestyle, and there was no urinary incontinence. CONCLUSIONS In this retrospective study, both IRA and IPAA showed to be feasible techniques in young patients with FAP. A prospective study with a sufficient follow-up is needed to compare both techniques in this specific group of patients.

Long-term Impact of Bile Duct Injury on Morbidity, Mortality, Quality of Life, and Work Related Limitations.

Objective: Assessment of long-term comprehensive outcome of multimodality treatment of bile duct injury (BDI) in terms of morbidity, mortality, quality of life (QoL), survival, and work related limitations. Background: The impact of BDI on work ability is scarcely investigated. Methods: BDI patients referred to a tertiary center after BDI were included (n = 800). QoL and work related limitations (HLQ) were compared with 175 control patients after uncomplicated laparoscopic cholecystectomy. Results: The mean survival after BDI was 17.6 years (95% confidence interval, CI, 17.2–18.0 years). BDI related mortality was 3.5% (28/800). Corrected for sex, ASA classification, treatment and type of injury, survival is worse in male patients (hazard ratio, HR 1.50, 95% CI 1.01–2.33) and progressively worse with higher ASA classification (ASA2: 5.25 (2.94–9.37), ASA3: 18.1 (9.79–33.3). Patients treated surgically had a significantly better survival (HR: 0.45 (95% CI: 0.25–0.80). BDI patients reported a significantly worse physical QoL compared with the control group and worse disease specific QoL. Loss of productivity of work was significantly higher among BDI patients. There also was a significant hindrance in unpaid work. A higher number of bile duct injury patients were receiving disability benefits after long-term follow-up (34.9% vs 19.6%, P = 0.004). Conclusions: Reconstructive surgery in BDI patients is associated with improved survival. Although the clinical outcome of multidisciplinary treatment of bile duct injury is good, it is associated with a significant decrease in QoL, loss of productivity in both paid and unpaid work and high rates of disability benefits use.

Prevention and Treatment of Major Complications After Cholecystectomy

Annually, over 19.000 patients undergo a cholecystectomy in the Netherlands, of which approximately 16.500 are performed laparoscopically. The complication rate after laparoscopic cholecystectomy (LC) is 2–12 % and the mortality rate about 0.2 %. General complications include wound infection, intra-abdominal abscess formation, and postoperative bleeding from the cystic artery which occurs in about 0.05 % and usually presents within a few hours after surgery. Laparoscopy-induced “access injuries” are visceral and vascular injuries that are mostly related to the puncture technique. Although the incidence of these complications is low, ranging from 0 to 0.05 % for the open technique versus 0.044 to 0.07 % for the closed technique, the overall mortality rate is high, ranging from 13 to 21 %. The most specific and devastating complication after cholecystectomy is bile duct injury (BDI). This complication is, especially in combination with vascular injury, accompanied by substantial morbidity, mortality, and a decrease in the life expectancy and long-term quality of life. The incidence reported in literature is dependent on its definition, study design, and study population and ranges from 0.16 to 1.5 % after LC versus 0.0 to 0.9 % after open cholecystectomy (OC). After the introduction of LC, initially there seemed to be an increase in the number of BDI. Go et al. evaluated the incidence of BDI after the introduction of LC in the Netherlands in 1990 until 1992 by using a written questionnaire which was sent to all 138 Dutch surgical institutions and reported an incidence of BDI of 0.86 %. Gouma et al. studied the incidence of BDI in 1991 using a questionnaire to all Dutch surgical departments to analyze the number of surgical reconstructions for BDI and therefore the true incidence of severe BDI and reported an incidence of 1.09 % after LC and 0.51 % BDI after OC. The higher incidence of BDI after LC in those days was mostly related to technical difficulties, unfamiliarity with the procedure, and the “learning curve” effect. A Cochrane systematic review from Keus et al. in 2006 suggests that the incidence of BDI has been stabilized since they found no difference in complications after LC or OC, with BDI occurring in 0.2 % in both groups. Nevertheless, annually 40–45 patients are still referred to the Academic Medical Center, without any sign of decrease in recent years. This suggests a higher incidence of BDI in the Netherlands than reported in the literature. As stated before, initially inexperience probably contributed to the high incidence of BDI, but other factors such as anatomical variation and techniques without using the critical view of safety (CVS) of Strasberg as the standard of care seem to be responsible for the current incidence of BDI. Furthermore, there appears to be a lack of knowledge of escape techniques in difficult cholecystectomies to prevent BDI. Buddingh et al. recently conducted a nationwide survey in which 97.6 % of Dutch surgeons reported to use the technique of CVS. Hereby the incidence of BDI in the Netherlands might decline in the future.

Partial Liver Resection because of Bile Duct Injury

Aim: To analyze the outcome of partial liver resection (PHx) after bile duct injury (BDI) in patients after multimodality treatment. Methods: Between 1990 and 2012, 800 BDI patients were referred to our tertiary center. Patient characteristics and long-term outcomes were described. Results: PHx was performed in 11 patients (1.4%), mean age 48.3 years (range 29.3-83.5 years), mainly because of complex injury [Amsterdam classification type D (n = 10, 91%), Strasberg type E (n = 7, 64%) and Bismuth type IV (n = 8, 73%)]. In 7 patients (64%), concomitant vasculobiliary injury had occurred in the right hepatic artery (n = 3), proper hepatic artery (n = 1), portal vein (PV; n = 2) and the right hepatic artery and PV simultaneously (n = 1). Early PHx was performed in 2 patients and delayed resection in 9 patients after a median of 57.8 months (range 3.9-183.4 months). The in-hospital mortality was 18% (n = 2) and long-term mortality 9% (n = 1). There were no significant differences in postoperative complications between early and late resection. Conclusions: Indications for PHx after BDI in patients referred to a tertiary center are relatively low (1.4%) and generally apply to vasculobiliary injury. The implications for treatment are important, so it is worthwhile to classify vascular injuries in the management of BDI.

Percutaneous-endoscopic rendezvous procedure for the management of bile duct injuries after cholecystectomy: short- and long-term outcomes

BACKGROUND Bile duct injury (BDI) remains a daunting complication of laparoscopic cholecystectomy. In patients with complex BDI, a percutaneous-endoscopic rendezvous procedure may be required to establish bile duct continuity. The aim of this study was to assess short- and long-term outcomes of the rendezvous procedure. METHODS All consecutive patients with BDI referred to our tertiary referral center between 1995 and 2016 were analyzed. A rendezvous procedure was performed when endoscopic or radiologic intervention failed, and when deemed feasible by a dedicated multidisciplinary team including hepatopancreaticobiliary surgeons, gastrointestinal endoscopists, and interventional radiologists. Classification of BDI, technical success of the rendezvous procedure, procedure-related adverse events, and outcomes were assessed. RESULTS Among a total of 812 patients, rendezvous was performed in 47 (6 %), 31 (66 %) of whom were diagnosed with complete transection of the bile duct (Amsterdam type D/Strasberg type E injury). The primary success rate of rendezvous was 94 % (44 /47 patients). Overall morbidity was 18 % (10 /55 procedures). No life-threatening adverse events or 90-day mortality occurred. After a median follow-up of 40 months (interquartile range 23 - 54 months), rendezvous was the final successful treatment in 26 /47 patients (55 %). In 14 /47 patients (30 %), rendezvous acted as a bridge to surgery, with hepaticojejunostomy being chosen either primarily or secondarily to treat refractory or relapsing stenosis. CONCLUSIONS In experienced hands, rendezvous was a safe procedure, with a long-term success rate of 55 %. When endoscopic or transhepatic interventions fail to restore bile duct continuity in patients with BDI, rendezvous should be considered, either as definitive treatment or as a bridge to elective surgery.

Long-term follow-up and risk factors for strictures after hepaticojejunostomy for bile duct injury: An analysis of surgical and percutaneous treatment in a tertiary center

Background: Hepaticojejunostomy is commonly indicated for major bile duct injury after cholecystectomy. The debate about the timing of hepaticojejunostomy for bile duct injury persists since data on postoperative outcomes, including postoperative strictures, are lacking. The aim of this study was to analyze short‐ and long‐term outcomes of hepaticojejunostomy for bile duct injury, including risk factors for strictures. Method: Analysis of outcome of hepaticojejunostomy in bile duct injury patients referred to a multidisciplinary team. Results: Between the years1991 and 2016, 281 patients underwent hepaticojejunostomy for bile duct injury. Clavien‐Dindo grade III complications occurred in 31 patients (11%) and 90‐day mortality occurred in 2 patients (0.7%). After a median follow‐up of 10.5 years (interquartile range 6.7–14.8 years), clinically relevant strictures were found in 37 patients (13.2%). Strictures were treated with percutaneous dilatation in 33 patients (89.2%), and 4 patients (1.4%) were reoperated. The stricture rate in patients undergoing hepaticojejunostomy <14 days, between 14–90 days, and >90 days after bile duct injury was 15.8%, 18.7%, and 9.9%, respectively. The stricture rate for early versus intermediate and late repair did not differ (P = 0.766 and 0.431, respectively). The stricture rate for repair after 14–90 days, however, was higher compared with repair >90 days after bile duct injury (P = 0.045). In multivariable analysis male gender was the only independent variable associated with stricture formation (OR 6.7, 95% CI 1.8–25.4, P = 0.005). Conclusion: Hepaticojejunostomy is a relatively safe treatment of bile duct injury. Timing of surgery and intermediate repair affect long‐term stricture rate; most anastomotic strictures can be treated successfully with percutaneous dilation.