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54 Remnant Pancreatic Cancer After Surgical Resection forPancreatic Cancer
403
local recurrence after second resection was comparable to that of patients with unresectable RPC or patients with extra­pancreatic recurrence.

54.1.2 Designations

In previous reports, various designations were used to describe RPC, including ‘remnant pancreatic cancer’ [10,
28, 32], ‘pancreatic cancer (ductal adenocarcinoma) in the
remnant pancreas’ [22, 27], ‘pancreatic cancer arising in the remnant pancreas’ [26], ‘carcinoma developing in the rem­nant pancreas’ [7, 11, 18], ‘metachronous pancreatic cancer’ [12], ‘second primary pancreatic ductal carcinoma’ [24], ‘recurrent peancreatic cancer’ [31, 34], ‘(isolated) local recurrence in the remnant pancreas’ [29, 30, 33], and ‘high­risk lesions in the remnant pancreas’ [21]. The use of differ­ent designations for RPC may be attributable to the fact that this malignancy was recently recognized and it includes lesions with different developmental mechanisms. For fur­ther research on this pathology, unication of the designation is desirable.

54.1.3 Incidence

According to previous cohort studies, the proportions of patient who developed RPC among those who underwent pancreatic resection for PC ranged 0.7–26.7% (Table54.1). Ishida etal. [24] calculated the cumulative incidence rates of RPC using the Kaplan–Meier method and reported a 5-year cumulative incidence rate of 17.7%. Although the propor­tions of patients with RPC were less than 6% in most studies,
two studies of early-stage PC reported much higher propor­tions (26.7% and 15.5%) [23, 25]. Our recent study found that the cumulative incidence of RPC after pancreatic resection was comparable between patients with early- and advanced-stage PC, whereas proportion of patients who developed RPC were signicantly higher in early-stage PC than advanced-stage PC [28]. It is suggested that the higher proportion of patients who developed RPC after early-stage PC was attributable to the higher number of long-term survi­vors in this cohort. Therefore, it is expected that the number of patients who develop RPC after surgical resection for PC will further increase if further improvements in the prognosis of PC are achieved.
The interval between the initial resection of PC and devel­opment of RPC ranged from 6 to 240months (Table54.1). It is suggested that RPC can develop more than 5years after the initial resection of PC.

54.1.4 Predictive Factors

Identication of the predictive factors of RPC may facilitate the early detection of RPC and assist in the creation of post­operative surveillance schedules. Matsuda etal. analyzed the long-term outcomes of 379 patients who underwent partial pancreatectomy for pancreatic ductal adenocarcinoma (PDAC) and identied 14 patients (3.96%) who developed RPC [27]. According to multivariate analysis, concomitant IPMN was an independent predictive factor for RPC after partial pancreatic resection for PDAC. In addition, they microscopically compared background pancreatic paren­chyma between patients with PDAC concomitant with IPMN and those with PDAC without IPMN, observing that the den-
Table 54.1 Cohort studies of the development of remnant pancreatic cancer after resection for pancreatic cancer
Number of Number of cases of initial pancreatic resection for
Author Year Thomas etal. [33] 2012 700 5 0.7 NA 68 (7–81) 5 Miyazaki etal. [29] 2014 284 11 3.9 9/2 32 (7–89) 11 Hashimoto etal.
[22] Shima etal. [31] 2015 185 6 3.2 6/0 25 (12–60) 6 Ishida etal. [24] 2016 130 6 4.6 6/0 43.5 (14–60) 4 Suzuki etal. [32] 2016 826 23 2.8 23/0 53.6 (15–240) 12 Nakayama etal. [30] Ikemoto etal. [23] 2018 30 8 26.7 NA 56.5 (16–85) 5 Kanno etal. [25] 2018 200 31 15.5 NA NA NA Gotoh etal. [21] 2019 411 22 5.4 NA NA 12 Matsuda etal. [27] 2020 379 14 3.7 12/2 42.5 (20–160) 10 Miyasaka etal. [28]
pancreatic cancer
2014 227 8 3.5 7/1 23.5 (17–39) 6
2018 194 11 5.7 11/0 24 (6–41) 11
2020 321 19 5.9 17/2 51 (20–160) 13
cases of
remnant
pancreatic
cancer
Proportion of cases with remnant pancreatic cancer (%)
Margin status of the initial resection (R0/ R1)
Median interval (range) between the initial resection and appearance of remnant pancreatic lesions (months)
Number of cases of resection for remnant pancreatic cancer
404
Y. Miyasaka and M. Nakamura
sity of pancreatic intraepithelial neoplasia was signicantly higher in patients with PDAC and concomitant IPMN.Careful postoperative surveillance focusing on the development of RPC is recommended for patients who undergo partial pan­createctomy for PDAC concomitant with IPMN.

54.1.5 Treatment

Similar to initial PC, surgery, chemotherapy, and radiother­apy are used to treat RPC.For lesions restricted to the rem­nant pancreas, surgical resection is often performed. Although surgery for RPC may be difcult because of adhe­sion and anatomical changes and RPC possibility of recur­rence of the initial cancer, it has been reported that the short- and long-term outcomes of surgical resection for RPC after initial resection for PC were relatively favorable. Yamada etal. [34] conducted a multicenter study of patients who developed RPC after pancreatic resection for PC.Among the 90 patients who underwent surgical resection for RPC, postoperative complications (Clavien–Dindo classication III or greater) were observed in eight patients (9%), and the 30- and 90-day mortality rates were 0 and 1%, respectively. Zhou etal. [45] performed a pooled analysis of 19 studies of second pancreatectomy for RPC and found no perioperative mortality. Several authors compared the prognosis of patients who underwent resection for RPC with that of patients who underwent nonsurgical treatment and observed signicantly better prognosis among patients who underwent resection [27, 29, 30, 32, 34]. Suzuki etal. [32] reviewed publications on RPC and collected data for 49 patients who underwent completion pancreatectomy for RPC after resection for ini­tial PC.According to their analysis, the median survival time after resection for RPC was 32months. A pooled analysis by Zhou et al. [45] reported a 5-year overall survival rate of
40.6% for patients after second pancreatectomy. Although surgery for RPC was performed in selected patients, their outcomes appeared to be more favorable than those of patients who underwent initial pancreatic resection for PC.The most common surgical procedure for RPC is total remnant pancreatectomy (completion pancreatectomy). The long-term outcomes of total pancreatectomy including total remnant pancreatectomy have been improved by progress in the management of endocrine and exocrine insufciency [4648]. Hashimoto etal. reported that total remnant pancre­atectomy after distal pancreatectomy was linked to a longer operative time and greater blood loss than total remnant pan­createctomy after pancreaticoduodenectomy [49]. In addi­tion, several reports described laparoscopic and robotic total remnant pancreatectomy [5052].
Adjuvant chemotherapy after resection for PC became
a standard treatment after several studies highlighted its
efficacy [35]. However, the efficacy of adjuvant chemo­therapy after surgery for RPC is not certain. Nakayama et al. [30] analyzed 11 patients with resected RPC and found that patients who underwent adjuvant chemother­apy exhibited significantly longer survival than their counterparts. Conversely, a pooled analysis by Zhou et al. [45] reported that adjuvant chemotherapy did not have a significant effect on overall survival. Although neoadjuvant therapy was also performed for RPC in some cases, detailed analysis of its efficacy was not performed. Similar to primary PC, chemotherapy or chemoradiother­apy is indicated for locally advanced or metastatic RPC [22, 24, 32, 53].

54.2 Conclusion

To date, attention has been paid to the development of local recurrence or metastasis during postoperative surveillance after surgery for PC.Although most cases of recurrence or metastasis occur within 5 years after the resection of PC, RPC can develop a long time after surgery. Surgeons should pay attention to this condition and provide life-long surveil­lance for patients who undergo partial pancreatic resection for PC.

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Benign Biliary Diseases

AbdelHadiS.Al Breizat, SalamS.Daradkeh, andAliA.Al-Sarira
55
Abstract
Most of the benign biliary diseases are consequences of cholelithiasis and its treatment. Weight reduction inter­ventions have increased the incidence and added a new category of patients. Biliary injuries and strictures remain a big challenge and become more challenging because of liver transplant biliary complications. Different diagnos­tic modalities are used including intraoperative color Doppler ultrasound, intraoperative contrast studies, and uorescence using indocyanine green to delineate the biliary and vascular anatomy. Liver transplant is increas­ingly used to treat primary sclerosing cholangitis. One-stage laparoscopic management of cholelithiasis and choledocholithiasis decreased the likelihood of complications resulting from interventions on sphincter of Oddi. Total excision of choledochal cysts with hepaticojejunostomy presenting in adults withstood the proof of time.
Multidisciplinary team approach including surgeon, radiologist, and endoscopist with properly timed usage of different diagnostic and therapeutic modalities in a spe­cialized centers is the key for successful management.
patients. Biliary injuries and strictures remain a big chal­lenge and become more challenging because of liver trans­plant biliary complications. Different diagnostic modalities are used including intraoperative color Doppler ultrasound, intraoperative contrast studies, and uorescence using indocyanine green to delineate the biliary and vascular anatomy. Liver transplant is increasingly used to treat pri­mary sclerosing cholangitis. One-stage laparoscopic man­agement of cholecystolithiasis and choledocholithiasis decreased the likelihood of complications resulting from interventions on sphincter of Oddi. Total excision of chole­dochal cysts with hepaticojejunostomy presenting in adults withstood the proof of time. Multidisciplinary team approach including surgeon, radiologist, and endoscopist with properly timed usage of different diagnostic and thera­peutic modalities in a specialized center is the key for suc­cessful management.

55.2 Congenital Anomalies

55.2.1 Biliary Atresia

Biliary atresia (BA) is a neonatal disease with progressive

55.1 Introduction

Most of benign biliary diseases are consequences of chole­lithiasis and its treatment. Weight reduction interventions have increased the incidence and added a new category of
A. H. S. Al Breizat (*) HPB unit-Surgical Department-AL Bashir Hospital MOH, Amman, Jordan
S. S. Daradkeh The University of Jordan, Amman, Jordan e-mail: daradkeh@ju.edu.jo
A.A. Al-Sarira Royal Hospital, Amman, Jordan e-mail: ali.al-sarira@royalhospital.jo
© The Author(s), under exclusive license to Springer Nature Singapore Pte Ltd. 2022 M. Makuuchi et al. (eds.), The IASGO Textbook of Multi-Disciplinary Management of Hepato-Pancreato-Biliary Diseases,
https://doi.org/10.1007/978-981-19-0063-1_55
obstructive cholangiopathy of the extrahepatic biliary tree as well as brosis of the liver parenchyma that occurs in 1 per 10,000 live births. Although the etiology and pathogen­esis remain unknown, there is experimental evidence for a primary perinatal infection as well as cellular and humoral autoimmunity. Presentation is usually in the early neonatal period with prolongation of neonatal jaundice. Kasai hepa­toportoenterostomy (HPE) achieves restoration of bile ow in about 50%–70% of infants depending on the age at time of surgery. Successful HPE is not curative but it is neces­sary for transplant free survival [1]. BA remains the leading indication for liver transplant in pediatric recipients accounting for 32.3% of pediatric liver transplants. Better outcomes reported following maternal liver-related liver transplantation [2].
407
408
A. H. S. Al Breizat et al.

55.2.2 Choledochal Cyst

Choledochal cyst (CC) is believed to be congenital cystic dilatation of the biliary tree with a frequency of 1in 150,000in western countries and has a female to male ratio of 4:1. Pathogenesis of CC is unknown. However, anomalous pan­creaticobiliary junction (APBJ) leading to chronic pancreato­biliary reux may explain it as 70% of patients with CC have APBJ [3]. While children usually have symptoms and signs, adults tend to be asymptomatic. The classical triad of presen­tation (jaundice, abdominal pain, and mass) is rare to be pres­ent all together and most cases still diagnosed incidentally. According to the rened Todani classication, Type I and Type IV are the most common and frequently associated with APBJ,whereas Types II, III, and V are less frequent [4].

55.3 Diagnosis

Liver function tests may be useful but not specic. Abdominal ultrasound is a useful preliminary test. Endoscopic ultraso­nography (EUS) helps to differentiate between choledochal and pancreatic cysts. Computed tomography (CT) detects CC and associated malignancy with an accuracy >90%. Magnetic resonance cholangiopancreatography (MRCP) is the most sensitive and specic (90–100%) noninvasive modality [5]. Endoscopic retrograde cholangiopancreatogra­phy (ERCP) is the gold standard but it is reserved for delin­eating biliary anatomy when MRCP fails or for relieving biliary obstruction [5].

55.4 Complications

Adult patients may develop the following complications: hepatic abscesses, cirrhosis, portal hypertension, recurrent pancreatitis, cystolithiasis, hepatolithiasis, and cholelithia­sis. There is an increased risk of biliary tract malignancy in patients with CC (10–20%) which increases signicantly with age and presence of APBJ [4, 6]. Malignancy occur not only in the cyst wall but also in the remainder of the hepatobiliary and pancreatic tree with gallbladder cancer being reported more frequently (67%) in patients with CC [4]. Risk of malignancy is higher for types I and IV CCs, whereas it is negligible for other types [6].

55.5 Management

Surgery is the mainstay, not only because of the risk of malignancy but also to prevent recurrent complications. Complete excision of the extrahepatic biliary tree to the level of the pancreaticobiliary junction with cholecystectomy and
Roux-en-Y hepaticojejunostomy is the standard therapy in Types I and IV [6]. Type II CC is treated with simple cyst excision and primary repair. Small type III CC can be man­aged effectively with endoscopic sphincterotomy, while lesions >3 cm need surgical excision. For type V, partial hepatectomy is indicated for conned CC or liver transplant if the entire intrahepatic biliary tree involved. In the absence of malignancy, the 5-year overall survival is more than 90%. But it is poor if malignancy coexists [6]. Patients need life­long follow-up as the rest of the pancreaticobiliary tree is still at risk of subsequent cancer development (about 11%) 25 years post resection and for early detection of anasto­motic stricture [7].

55.5.1 Gallstones

Gallstones (GS) affect 10–20% of adult Caucasians with variable prevalence throughout the world. The highest preva­lence is in North American Indians, whereas it is the lowest among Asia and sub-Saharan Africa. In addition to ethnicity, female sex, increasing age, and overnutrition are the main risk factors. Only 1–2% develop GS related complications requiring surgery. The prevalence overall was 7.9% of men and 16.6% of women [8].

55.6 Pathogenesis

Gallstones are classied as cholesterol (80–85%) that forms mainly in the gallbladder or pigment stones. The mecha­nisms contributing to the formation of cholesterol gallblad­der stones are cholesterol supersaturation of bile, gallbladder hypomotility, and destabilization of bile by kinetic protein factors [9]. Stasis of bile in the gallbladder favors stone for­mation, as indicated by stone formation during pregnancy, rapid weight loss, or total parenteral nutrition. Gallbladder hypomotility is probably due to absorption of cholesterol from supersaturated bile by the gallbladder wall that paralyz­ing gallbladder contractile function [9].
Black pigment stones consist mainly of polymerized cal­cium bilirubinate. Hemolytic anemias or ineffective eryth­ropoiesis are the most common sources of excess unconjugated bilirubin. Another pathway involves ileal dis­ease or resection causing spillage of bile salts into the colon that results in increased enterohepatic cycling and biliary secretion of bilirubin [9].
Brown pigment stones are mostly formed within the bile ducts as a consequence of bacterial infection and hydrolysis of glucuronic acid from bilirubin by bacterial b- glucuronidase. Intrahepatic brown pigment stones are related to infestation with the parasites Clonorchis sinensis and Ascaris lumbri- coides [9].
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55.7 Natural History ofGallstones
Over 80% of GS are asymptomatic [9]. Around 30% of peo­ple with asymptomatic GS will require surgical intervention in their lifetime [10]. So, prophylactic cholecystectomy is not recommended for this group of asymptomatic patients [8].
Biliary pain “colic” is a constant dull aching pain in the epigastrium or right upper quadrant for more than half an hour radiating to the back or right shoulder that might be associated with nausea and vomiting but not fever [11]. GS can also cause nonspecic abdominal symptoms [8]. Abdominal ultrasonography is the imaging method of choice with diagnostic accuracy for the detection of GS exceeds 95% [8]. EUS or MRCP can detect microlithiasis [9].

55.8 Complications

Complications of gallstone disease include: acute cholecysti­tis, Mirizzi syndrome, biliary pancreatitis, acute ascending cholangitis, and gallstone ileus.

55.9 Bile Duct Stones

Common bile duct stones (CBDS) are estimated to be pres­ent in 10–20% of patients with symptomatic GS [11]. Symptoms of CBDS are mainly epigastric and/or right upper quadrant abdominal pain and obstructive jaundice can be the presentation [9]. CBDS are usually characterized by eleva­tion of liver enzymes and dilatation of the diameter of the common bile duct. The most reliable method of diagnosis is MRCP or EUS [11].

55.11 Intrahepatic Stones

Prevalent but decreasing in south east Asia, rare in the west, represent a challenging problem because usually associated with biliary stricture, recurrent cholangitis, secondary biliary cirrhosis and may progress to cholangiocarcinoma. Four fac­tors seem to contribute to its pathogenesis (stasis, infection, anatomic biliary variation, and bile metabolic defect). Liver resection is the ideal treatment for isolated unilateral disease. Minimally invasive procedures like percutaneous or endo­scopic lithotripsy may be the ideal treatment for diffuse bilateral disease [12].
55.12 Gallstones inPregnancy
Cholecystitis is considered the second most common surgi­cal emergency in pregnancy that ranges from 0.05–0.8%. Conservative management versus LC has the same morbid­ity and mortality on the mother and fetus. LC proved its safety in all trimesters of pregnancy, but if possible, to be done during the second trimester [13, 14].
55.13 Gallbladder Stones andBiliary Cancer
Evidence from cohort studies suggest an increased incidence of gallbladder cancer and intra and extrahepatic cholangiocarcinoma in patients with GS, this risk diminishes several years after cholecystectomy [15].

55.13.1 Benign Biliary Strictures (BBS)

55.10 Management

Symptomatic GBS are managed by laparoscopic cholecys­tectomy (LC) which represents the gold standard. Asymptomatic GS should be observed and until now there are no randomized controlled trials performed on whether asymptomatic GS should be managed in the general popu­lation [9].
Symptomatic CBDS represent around 10% [11]. ERCP with endoscopic sphincterotomy and extraction of the stone is one option of treatment although there is a risk of compli­cations like acute pancreatitis, bleeding, and perforation. Open or laparoscopic common bile duct exploration depend­ing on the experience of the surgeon is performed when ERCP is failed. There is strong evidence in the literature now that laparoscopic one-stage surgery for both the GBS and CBDS is the preferred treatment [11].
BBS most often arise from postoperative or inammatory etiologies. Surgery-related BBS most frequently results from LC (0.4–0.6%), bile duct surgery, and liver transplant [16,
17]. BBS are iatrogenic (80%) related to LC while chronic
pancreatitis-related are the most common nonsurgical BBS (13–21%) [18].

55.14 Iatrogenic Biliary Injury

Iatrogenic biliary injury occurs when surgeons fail to appro­priately avoid the main bile duct (MBD) and its blood supply during cholecystectomy [19]. It causes signicant patient morbidity, mortality, and decreased survival rate, requiring complex and costly management [20, 21].
Adequate dissection to achieve the critical view of safety described by Strasberg, Rouviere’s sulcus as the rst land­mark and using indocyanine green uorescence contrast are
410
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widely believed to decrease the risk of MBD injury in LC [2224]. Also, indication for LC and presence of anatomical variation are considered risk factors. Routine use of intraop­erative cholangiogram (IOC) does not prevent MBD injury but has the ability to intraoperatively recognize it [25].
The outcome of reconstruction depends on the type of injury, associated vascular injury, and the anatomical loca­tion. Bismuth and Strasberg classications are the most com­monly used systems to describe iatrogenic bile duct injuries [26, 27].
Injuries are recognized intraoperatively only in approxi­mately one third of patients and in 70–80% of cases with true partial injury or transection of the MBD.It should be consid­ered if more than a single duct is seen or suspected and if bile is observed to be leaking from the area of the porta hepatis and hepatoduodenal ligament [28]. A majority of these unrecognized injuries involve bile leaks from the cystic duct and rarely small ducts of Luschka and may present early with a postoperative biliary stula, symptoms of biliary peri­tonitis or jaundice but they can be vague and the diagnosis can be challenging. Ligation of the bile duct will present early with jaundice; however, later presentation may occur as a result of stricture formation from a partial injury, localized inammation, or ischemic insult [28]. In many patients there is a delay until referral and this delay is not inconsequential as the opportunity for an early repair is lost and results in poor outcome [28, 29].
Work up for patients depends on patient status. Abdominal ultrasound may visualize uid collection. Doppler imaging can aid in diagnosis of concomitant vascular injury [30]. CT scan should be done in patient with diffuse abdominal pain and tenderness. MRCP allows for conrmation and delinea­tion of the anatomy proximal and distal to the injury [31]. Although ERCP can only assess biliary tree anatomy distal to an injury, it can be of therapeutic value at the time of diag­nosis [32]. Hepatobiliary iminodiacetic acid (HIDA) scan has increased sensitivity compared with MRCP for demon­strating ongoing bile leak particularly in the early postopera­tive period [33].
Controlling biliary injury and associated sepsis is the rst treatment aim which can be achieved by: percutaneous tran­shepatic cholangiography (PTC) and drainage in case of cholangitis with MBD occlusion, percutaneous drainage in case of intra-abdominal abscess or biloma, or prompt emer­gent operative exploration in case of biliary peritonitis. Establishing bile ow from the biliary tree to the alimentary tract is the next step.
Who, when, and where? are important factors to deter­mine the outcome of the repair [34, 35]. Early referral to a tertiary care center with a multidisciplinary team manage­ment is the standard of care. Timing of repair can be chal­lenging and remains controversial [35]. Repairs performed
early, within 72hours of injury, or late, more than 6weeks after the injury with limited number of concomitant vascular injuries had signicantly fewer long-term strictures com­pared with intermediate repairs [36]. No difference in the outcome was noticed with intermediate repairs compared with late repair provided it is done by hepatobiliary surgeons. But worse outcome in all categories when repair was per­formed early by the primary surgeon [35, 37].
Nonoperative management in the form of percutaneous and ERCP therapy for biliary injury can be used as a deni­tive treatment or as a temporary management. ERCP, sphinc­terotomy, balloon dilatation, and stenting were a successful denitive treatment in about 82% of patients with bile duct injury but without transection and 80% of patients with pos­tcholecystectomy MBD stricture [32]. Denitive operative reconstruction should be performed under optimal condi­tions [21]. Operative management remains the gold standard for repair of iatrogenic biliary injury when complete MBD transections and occlusions present and injury cannot be managed with ERCP.Simple repair over a T tube is appropri­ate for non-thermal injuries involving less than 50% of the diameter of the CBD and for small lateral sidewall injuries [38]. Primary end to end tension free anastomosis is possible in case of sharp transection injury without involvement of hepatic duct conuence and no signicant tissue loss [39]. The gold standard for operative repair of iatrogenic MBD injury is a hepaticojejunostomy with 70 cm Roux limb to minimize the risk of enteric reux. Lowering the hilar plate allows easier identication of the left and right hepatic ducts [40]. Anastomotic strictures are reported in 4%–38% of patients who underwent hepaticojejunostomy with a revision rate of 20–25% [19, 29]. Liver resection and transplantation may be necessary [29]. Concomitant vasculo-biliary injury and lesions proximal to the hepatic duct conuence are the signicant risk factors for such sequalae [28].

55.15 Mirizzi Syndrome (MS)

MS is a rare complication of symptomatic gallstone. It is due to impacted gallstone in the infundibulum causing com­pression on the bile duct and chronic inammation of the gallbladder wall. Type I is external compression of the bile duct only while other types are associated with cholecystobiliary stula. They present most commonly with obstructive jaundice or picture of acute cholecystitis. ERCP is the gold standard for diagnosis and therapeutic interven­tion. As it is most commonly diagnosed during surgery and carries a high risk for biliary injury (17%), conversion to open cholecystectomy is still the standard of care. For type I, classical open cholecystectomy or subtotal cholecystec­tomy is recommended. For types II and III, subtotal chole-
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cystectomy is recommended leaving a small remnant of gallbladder wall over the cholecystobiliary stula. But if the defect is large and for type IV, it is recommended to do bil­ioenteric anastomosis [41].

55.16 Liver Transplantation Related BBS

BBS after liver transplantation occurs at an incidence of 10%–40% most commonly at the anastomotic site [17]. Anastomotic strictures are typically single focal stricture and more frequently associated with living-donor livers. Endoscopic therapy is an effective rst-line treatment with high stricture resolution rate of 66.7–100%. Late-onset stric­tures (6months post transplantation) are likely to require more endoscopic interventions than those presenting in the early post-transplant period [42].
Non-anastomotic strictures are dened as those occurring 5 mm proximally to the anastomosis and are associated with ischemic events. They are characterized by multiple extrahepatic and/or intrahepatic strictures with recurrent sludge or stone formation. Late-onset non-anastomotic stric­tures (1 year post transplantation) are more resistant to endoscopic therapy than anastomotic types with higher rates of stricture recurrence [42].

55.17 Primary Sclerosing Cholangitis (PSC)

PSC is a progressive, immune-mediated, obliterative inam­matory process of intrahepatic and extrahepatic biliary ducts. Patients usually present between 35 and 47years of age, with male predilection. It is highly associated with inammatory bowel disease and highly regarded as a premalignant lesion for hepatobiliary and colorectal malignancy. The gold stan­dard for the diagnosis of PSC is cholangiography that shows short annular strictures alternating between normal and dilated intervening segments resulting in the classical appearance of “beads on a string.” MRCP is routinely recom­mended as the initial imaging study of choice while ERCP is recommended because of the likelihood of requiring inter­vention [43]. Ursodeoxycholic acid is used to treat pruritis and is associated with improvement in biochemical and his­tological appearance. Liver transplantation remains the only curative therapy at present [43].

55.17.1 Biliary Dyskinesia

Biliary dyskinesia is a functional disorder of gallbladder and biliary sphincter of Oddi (SOD). As it is a diagnosis of exclu­sion, it is recommended to follow Rome IV consensus crite­ria when investigating patients with biliary type pain to
exclude stones or microlithiasis within the gallbladder or biliary tree or any other structural abnormalities [44].
In case of functional gallbladder disorder, a low ejection fraction on gallbladder scintigraphy (<40%) is no longer required for diagnosis, but remains an important supportive criterion [50]. Cholecystectomy is considered the mainstay of management with reported symptomatic relief of (91–98%).
Functional biliary SOD is incompletely understood. In the current Rome IV criteria, the classical types of SOD (types I, II, and III) are no longer used. Previous type I (pap­illary stenosis) is a pure mechanical obstruction. The diagno­sis of SOD relies on clinical suspicion, exclusion of functional and organic mimickers. In the EPISOD trial, patients diagnosed with type III SOD (normal laboratory studies, normal bile duct) did not benet from ERCP and sphincterotomy. Also, no benet was observed in the limited number of patients with type II [45]. In view of procedure­related complications and unsatisfactory results, ERCP and sphincterotomy should only be performed for carefully selected patients at specialized centers.

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