J Ped Surg Case Reports 4 (2016) 17e21

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Journal of Pediatric Surgery CASE REPORTS

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Cholecysto-appendicostomy as partial internal biliary drainage in Progressive Familial Intrahepatic Type 1: A case report and review of literature

Yee Ian Yik a,*, Mohd Yusran Othman a,b, Ruey Terng Ng c, Way Seah Lee c,d a Division of Paediatric and Neonatal Surgery, Department of Surgery, Faculty of Medicine, University of Malaya, 50603 Kuala Lumpur, Malaysia b Department of Paediatric Surgery, Institute of Paediatrics, Hospital Kuala Lumpur, 50586 Kuala Lumpur, Malaysia c and Unit, Department of Paediatrics, Faculty of Medicine, University of Malaya, 50603 Kuala Lumpur, Malaysia d University of Malaya Paediatrics and Child Health Research Group, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia article info abstract

Article history: Intractable pruritus secondary to salts retention in Progressive Familial Intrahepatic Cholestasis Received 26 September 2015 (PFIC) can be relieved surgically by diverting bile drainage from to reduce bile salts reabsorption Received in revised form into entero-hepatic circulation. We are reporting on the successful biliary diversion in a child with PFIC, 18 November 2015 with the use of the as a conduit to drain bile from to the colon (cholecysto- Accepted 18 November 2015 appendicostomy). Ó 2016 The Authors. Published by Elsevier Inc. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). Key words: Biliary diversion Cholecysto-appendicostomy Intractable pruritus Liver transplant Progressive familial intrahepatic cholestasis

Progressive Familial Intrahepatic Cholestasis (PFIC) is an drainage, PIBD) in a child with PFIC and reviewed the literature autosomal recessive disorder, typically presented during infancy of BD surgery. with jaundice, pruritus and failure to thrive [1]. It is charac- terized by impaired bile acid metabolism and excretion causing 1. Case report intrahepatic cholestasis [1,2]. The concentrated biliary com- pounds lead to disabling pruritus and hepatocellular damage, A 7-year-old girl presented with jaundice and failure to thrive subsequently progresses to and death in early since the age of 10 months old. She was born at term with a birth childhood or adolescence [2,3].MutationintheATP8B1 gene, a weight of 2.25 kg. She had neonatal jaundice but did not require regulator of intestinal bile acid absorption, has been identified admission or phototherapy. Her parents were healthy and unre- in PFIC Type 1, also known as Byler [4]. Before 1990, lated, and there was no family history of . She was liver transplant (LTX) was the only treatment option for PFIC admitted at the age of 10 months old for acute but [2]. However, in the past 2 decades, surgical intervention with found to be jaundiced and her weight was 4.6 kg (below 3rd cen- biliary diversion (BD) had been considered for symptomatic tile). Liver function test (LFT) showed raised levels of Aspartate relief and was found to curtail liver impairment, and delaying Aminotransferase (AST) and Alkaline Phosphatase (ALP) but with the need for LTX [2,3]. In this report, we share our experience normal level of Gamma-Glutamyl Transpeptidase (GGT, 5 U/L). She of cholecysto-appendicostomy (CA, a partial internal biliary had conjugated hyperbilirubinemia (82 umol/L). Hepatobiliary ul- trasound showed no evidence of biliary obstruction or focal liver disease. Additionally, screenings of her thyroid function, immu- nology and inborn error of metabolism were all normal. Percuta- * Corresponding author. Tel.: þ60 3 79492070; fax: þ60 3 79586360. neous liver biopsy was reported with paucity of intrahepatic bile E-mail address: [email protected] (Y.I. Yik). ducts. Subsequent assessments for Alagille syndrome included

2213-5766/Ó 2016 The Authors. Published by Elsevier Inc. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). http://dx.doi.org/10.1016/j.epsc.2015.11.009 18 Y.I. Yik et al. / J Ped Surg Case Reports 4 (2016) 17e21

Laparotomy was performed via a right upper transverse mus- cle-cutting incision. Operative cholangiogram showed patent biliary tree with grossly distended and elongated gallbladder (Fig. 1). The appendix was identified, mobilized and brought up close to the gallbladder via a small mesenteric defect created medial to caecum/ascending colon to facilitate a tension-free, non-kinking (Fig. 2). Liver biopsy was obtained. The surgery was uneventful and her postoperative recovery was excellent. At recent follow-ups, she reported markedly reduced pruritus, with improved quality of life. Moreover, her parents observed less intense scratching at home and she had better quality of sleep. Clinically, she was less jaundice and her skin was less lichenified. Although her liver enzymes recorded minimal improvement but her bilirubin level has markedly reduced (Fig. 3). Her liver biopsy only showed evidence of chronic with fibrosis. She remained well 8 months after surgery with no symptoms to suggest progression of liver impairment.

2. Discussion

Intractable pruritus is one of the most disturbing and disabling symptom of PFIC [2,5], with persistent scratching leading to social and sleep disturbances, and skin lichenification. Medical therapy Fig. 1. Operative cholangiogram showed a distended, elongated gallbladder and patent biliary tree. with cholestyramine, phenobarbital, rifampin or ursodeoxycholic acid may relieve symptoms in 60% of patients [4,6]. LTX was the only surgical intervention until the late 1980s when surgery for BD spine x-rays, echocardiogram and ophthalmology examination was introduced and considered. BD involves diversion of biliary were normal. Importantly, genetic study found mutation in ATP8B1 drainage, bypassing the ileum to reduce bile salts reabsorption into gene, diagnostic for PFIC Type 1. entero-hepatic circulation and thus increases the elimination of bile She is under close follow-ups by the paediatrics gastroenter- acids from the body [2]. ology and hepatology team, together with the dietician. She has Various techniques of BD have been reported (Table 1). In 1988, persistent hyperbilirubinaemia with deranged liver enzymes Whitington and Whitington introduced partial external biliary (raised ALT and ALP). During her disease course, she developed drainage (PEBD): was used as a conduit to drain bile from severe skin pruritus, disturbing her social activity and sleep, and her gallbladder to an external stoma (cholecysto-jejuno-cutaneos- skin became lichenified due to persistent scratching. Despite tomy), with very encouraging short-term outcomes [7]. Successful treatment with antihistamines, ursodeoxycholic acid and chole- PEBDs were further reported but issues related to stoma or external styramine, her pruritus persisted and surgical referral was made for biliary fistula, such as stoma prolapse and high output stoma losses consideration of BD at the age of 7 years old. were documented, respectively [5,9]. In 2005, Metzelder et al.

Fig. 2. A e Illustrative diagram of cholecysto-appendicostomy. B e Intra-operative image showed end-to-end anastomosis with interrupted sutures (cholecysto-appendicostomy). Y.I. Yik et al. / J Ped Surg Case Reports 4 (2016) 17e21 19

Fig. 3. Progression of bilirubin levels before and after surgery. Marked reduction in bilirubin level was recorded after surgery.

Table 1 Various techniques of biliary diversion and the procedure-related outcomes.

Author Year Procedure Number of Follow-up Complications Remarks patient (n) duration Partial External Biliary Drainage (PEBD) Whitington et al. [7] 1988 Cholecysto-jejunostomy 63e8 years Postoperative hemorrhage from ostomy The reported (with a cutaneous end stoma) (n ¼ 1), postoperative bowel 6 cases include obstruction and acquired acute cholangitis 4 patients with (in 1 patient with underlying progressive arteriohepatic dysplasia) intrahepatic cholestasis and 2 patients with arteriohepatic dysplasia Metzelder et al. [8] 2005 Laparoscopic 4 1.5e2.5 months None mentioned Faster recovery time and cholecysto-jejunostomy minimal abdominal scar (with a cutaneous end stoma) Arnell et al. [9] 2008 Cholecysto-jejunostomy 13 11e21 months Stomal leakage and prolapse (n ¼ 1) (with a cutaneous end stoma) Hyponatremia due to excessive losses of bile fluid (n ¼ 5) Halaweish & Chwals [4] 2010 Hepatico-jejunostomy or 7 6 months 4 patients had stoma related complications cholecysto-jejunostomy (3 prolapse & 1 persistent (with a cutaneous loop stoma) efferent loop stomal reflux) 2 had high stoma output and died from gastroenteritis-related dehydration Sharma et al. [10] 2010 Cholecysto-appendicostomy 1 6 months None mentioned Less extensive bowel (with a cutaneous end stoma) resection Appendicular stoma had better cosmesis Clifton et al. [11] 2011 Button cholecystostomy 3 1e2.5 years Button dislodgement but easily replaced On 12e14 h drainage period per day Avoided enteric anastomosis Schukfeh et al. [12] 2014 Laparoscopic button 2 6 months None mentioned cholecystostomy Ileal exclusion (IE) Hollands et al. [6] 1998 Ileo-colonic anastomosis 5 6e22 months Bleeding from stappled anastomosis Reported late recurrence requiring re-operation (n ¼ 1) of symptoms in up to 60% of patients probably secondary to gradual adaptation of the ileum to the 15% resection [13] Ricca et al. [14] 2014 Ileo-cecostomy 1 7 months Ileocolic intussusception of the (100 cm of ileum bypassed) excluded ileum causing symptoms recurrence within 7 days. Ischemic intussusceptum resected leaving 10 cm terminal ileum intact, ileocolostomy taken down and had ileo-ileostomy (no bypassed segment) Partial Internal Biliary Drainage (PIBD) Bustorff-Silva et al. [2] 2007 Cholecysto-jejuno-colonic 2 NA Transient increase in number of bowel 1 patient had anastomosis movement in 1 patient internalization of PEBD (cholecysto-jejuno- cutaneoustomy) to a cholecysto-jejuno-colonic anastomosis (continued on next page) 20 Y.I. Yik et al. / J Ped Surg Case Reports 4 (2016) 17e21

Table 1 (continued )

Author Year Procedure Number of Follow-up Complications Remarks patient (n) duration Ganesh et al. [15] 2010 Cholecysto-jejuno-colonic 1 2 years Intermittent anastomosis Gun et al. [5] 2010 Cholecysto-jejuno-colonic 4 NA Diarrhea in 1 patient anastomosis (responded to cholestyramine) Mochizuki et al. [16] 2012 Cholecysto-jejuno-colonic 1 7 months HPE of colonic mucosa at 7 anastomosis months post-surgery showed foam cell infiltration similar to cholesterosis of gallbladder Diao et al. [17] 2013 Laparoscopic 20 12e104 months None reported to have anastomotic 85% success rate, cholecysto-colostomy stricture, cholangitis, younger age group (with antireflux Y-loop) diarrhea or intrahepatic reflux compared to other PIBD or PEBD series (median 1.47 years) Mousavi & Karami [3] 2014 Cholecysto-appendicostomy 1 9 months Stricture post (then convert to cholecysto-appendicostomy (symptoms cholecysto-jejuno-colonic recurred after 15 days post-surgery). anastomosis) Redo surgery done after a month, then Our case 2015 Cholecysto-appendicostomy 1 8 months None (so far) Single anastomosis Less extensive dissection No external biliary fistula

NA ¼ not available. introduced laparoscopic PEBD and documented shorter recovery without short-term complications, as reported by Mousavi and time with minimal abdominal scar [8]. Sharma et al., in 2010 re- Karami. Our technique is similar to the one reported by Mousavi ported a modification of PEBD using appendix as a successful and Karami but without additional myotomy on the appendix, and conduit (cholecysto-appendico-cutaneostomy), with less extensive we performed end-to-end anastomosis (fundus of the gallbladder bowel resection and anastomosis, and with better cosmesis [10]. to the spatulated tip of appendix), contrary to the end-to-side Button cholecystostomy as PEBD was reported by Clifton et al., in anastomosis. The appendix was brought through a surgically 2011 [11] and its laparoscopic approach was later introduced by created mesenteric defect, affixed with sutures before anastomosed Schukfeh et al., in 2013 [12]. Both authors considered their tech- to the gallbladder in a tension-free, non-kinking manner. Contin- niques as a much simpler approach with adequate bile drainage to uous bile drainage was evidenced by clinical improvement of her relieve symptoms. symptoms (less intense pruritus and better quality of sleep), further An alternative approach described by Hollands et al. for BD supported by the biochemical improvement of her LFT, with called Ileal Exclusion (IE) or Ileal Bypass [6]. In this technique, there marked reduction of bilirubin (by 8 folds). was no external stoma, with an ileo-colonic anastomosis bypassing approximately 15% of the ileum proximal to the ileocecal valve. 3. Conclusion Short-term outcome was promising but it failed to show long-term improvement, likely due to ileal adaptation and accommodation to In our case, cholecysto-appendicostomy shows good medium- re-absorb bile salts [13]. The bypassed ileum can lead to intussus- term outcome for intractable pruritus in PFIC. It avoids external ception, as reported by Ricca et al. [14]. biliary fistula (as in PEBD) and involves only a single anastomosis of PIBD was considered an attractive surgical option with post- appendix to the gallbladder. It is a promising surgical option for BD. diversion outcome as good as PEBD without an external biliary Long-term follow-up is required to determine the successful fistula [2]. In 2007, Bustorff-Silva et al. reported a new PIBD tech- outcome of this procedure. nique by the creation of an intestinal conduit between gallbladder and ascending colon [2], with the use of 15e20 cm of mid-jejunum, Conflicts of interest and it involved 3 anastomoses, which was a major disadvantage of All authors agreed and declared that no potential financial and this technique [2,3]. In 2013, Diao et al. described their technique of non-financial conflicts of interest. laparoscopic cholecysto-colostomy, whereby the gallbladder was anastomosed to descending colon with an antireflux Y-loop; the success rate recorded was 85% with minimal morbidity [17] Acknowledgments (Table 1). Mousavi and Karami in 2014 reported on the use of appendix as a conduit for PIBD, with an end-to-side cholecysto- The authors would like to acknowledge the assistance by appendicostomy. Additionally, they performed longitudinal myot- Professor Huey Ling Chen from Department of Paediatrics, National omy along the appendix with a wider anastomosis to the Taiwan University, College of Medicine and NTU Children’s Hospital, gallbladder in their attempt to prevent stricture [3]. The immediate for the work in mutational analysis of the patient. outcome was good, but symptoms recurred within 15 days and anastomotic stricture was confirmed at re-operation. A redo biliary diversion was performed with the technique as described by References Bustorrff-Silva et al. [1] Lee WS, Chai PF, Looi LM. Progressive familial intrahepatic cholestasis in In 2009, Lee et al. reported 5 cases of PFIC with poor outcome Malaysian patients-a report of five cases. Med J Malaysia 2009;64(3):216e9. because LTX and BD surgery were not widely practiced in Malaysia [2] Bustorff-Silva J, Neto LS, Olímpio H, de Alcantara RV, Matsushima E, De [1]. Our case will be the first successful PIBD operation performed in Tommaso AM, et al. Partial internal biliary diversion through a chol- ecystojejunocolonic anastomosis-a novel surgical approach for patients with Malaysia, and perhaps the second case of cholecysto-appendicos- progressive familial intrahepatic cholestasis: a preliminary report. J Pediatr tomy in the literature, with good medium-term outcome, and Surg 2007;42(8):1337e40. Y.I. Yik et al. / J Ped Surg Case Reports 4 (2016) 17e21 21

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