Ağustos 2014

46-50

Gülten CAN SEZGİN¹ , Alper YURCİ ¹, Eylem SEVİNÇ ² , Kemal DENİZ ³ , Derya KARADEMİR ⁴ , Zeki YILMAZ ⁵

Departments of ¹ Gastroenterology, ² Pediatric Gastroenterology, ³ Pathology, ⁴ Internal Medicine, and ⁵ General Surgery, Erciyes Univercity Hospital, Kayseri

Koledok kistleri safra kanallarının doğuştan dilatasyonudur ve aralıklı safra tıkanıklığına neden olabilir. Erken tanı ve tedavi edilmediğinde safra akı-mının bozulmasına; kronik karaciğer hasarı, fibrozis ve sonuçta biliyer siroza neden olabilir. Genellikle pediatrik popülasyonda tanısı konulmasına rağmen, %20-30 oranında erişkin yaş grubunda tespit edilebilir. Kadınlarda daha sık görülmektedir. Rezeke edilmeyen koledok kistlerinde kolanjiyokarsinom riski artmıştır. Tedavi koledok kistinin çıkarılması ve bilioenterik anastomozu içerir. Bu makalede rezeke edilmemiş koledok kistine bağlı geli-şen kolanjiyokarsinomlu iki olgu bildirildi.

Kolanjiokarsinom, koledok kisti, sarılık

Choledochal cysts are congenital dilations of the biliary ducts, which can cause progressive biliary obstruction and biliary cirrhosis. Cylindrical and spherical cysts of the extrahepatic ducts are the most common types (1). Choledochal cysts are more prevalent in Asia than in Western countries, and approximately 33-50% of reported cases are from Japan. They occur more often in women, with a male to female ratio of 1:3 to 4 (2,3). Cholangitis, rupture, pancreatitis, and gallstones are important complications of choledochal cysts and may occur even in early infancy, whereas chronic cholecystitis and cholangiocarcinoma may be long-term complications if the cyst is not fully removed (4). The incidence of malignant transformation is reported to be 2.5?26%. The malignant change occurs mainly within the choledochal cyst, but may occur in the gallbladder, pancreatic duct, and intrahepatic bile ducts. Multiple malignant transformations are also reported (5).

Choledochal cysts are considered to be rare biliary tract disorders with a high mortality rate due to their late diagnosis. They are defined as congenital anomalies of the biliary tract, characterized by varying degree of cystic dilatation in various segments of the biliary tract, with extrahepatic or intrahepatic divisions (6). Our cases are among the rare examples of choledochal cysts with cholangiocarcinoma resulting in the deaths of the patients due to the late symptoms and treatment, which confirm the findings of the earlier literature. This report intends to document these examples and highlight the importance of early diagnosis and treatment. Regarding the frequency of choledochal cysts, the disease is observed in about 1 in 15,000 live births in Western countries, while the ratio is as high as 1 in 1000 live births in Japan (7). Unfortunately, the ratio of the disease is not extensively reported in Turkey. These two cases in our hospital were seen between 2006 and 2012. The literature indicates that the disease is typically more common among women, but there has been an increase recently in the number of male patients. Our study included one male and one female. Extrahepatic bile duct cysts were first classified by Alenso-Lej et al. in 1959, and revised by Todani et al., who described a system of classification of these cysts into five discrete types (Table 2). The most common are types I and IVA, whereas types II and V are generally rare (8,9). The more common type I and type IVA cysts are associated with an abnormal pancreaticobiliary duct junction, and a long common channel, as well as mixing of pancreatic and biliary juice, leading to mucosal breakdown and dilatation. Type I cysts relate to an abnormal arrangement of the pancreatobiliary ducts, also known as ?common channel,? which is seen in up to 92% of the patients with choledochal cysts. This can present in childhood with high grade reflux or later in adulthood with low grade reflux (10-12). Our cases both belong to type I. Choledochal cysts can be present at any age, and both the pediatric and adult populations presented most commonly with abdominal pain, nausea, vomiting, and jaundice (13). The type of symptoms depends largely on the age at presentation. Abdominal pain has been reported to be the most frequent symptom at presentation and is the main symptom in adults, whereas jaundice is reportedly the main presenting symptom in infants (14). It should be noted that both of the patients in this study were diagnosed with cholangiocarcinoma after their admission to the hospital with complaints of abdominal pain and weight loss, yet neither of them showed previous symptoms like abdominal pain or jaundice that would indicate choledochal cysts. Once a preliminary diagnosis is made using ultrasound (US) scanning, other supportive studies may be ordered, including abdominal computed tomography (CT) scans, magnetic resonance imaging (MRI) studies, or MRCP examinations. US has been the imaging modality of choice in children, whereas ERCP was used most commonly in adults. Percutaneous liver biopsy is contraindicated because of the risks of biliary injury and peritonitis (11,15,16). Treatment of choledochal cysts is complete surgical excision of the cyst mucosa, with a Roux-en-Y choledochojejunostomy proximal to the most distal lesion (17). Each of these drainage techniques retained the wall of the cyst with its abnormal mucosa. Poor drainage leading to stasis and persistent cyst inflammation resulted in stricture formation, biliary lithiasis, and an increased risk of malignant evolution within the cyst wall (18). Clinically, the common complications of congenital choledochal cyst were recurrent cholangitis, recurrent pancreatitis, rupture, stone formation, and malignant transformation (19,20). Of these, the most serious complication is malignant transformation. Both cases indicated no complication or clinical complaints before the development of the cholangiocarcinoma related to choledochal cysts. Although the disease is typically observed in the 5th-7th decades, cases in this study were in their forties. For cholangiocarcinoma patients diagnosed at an early age, primarily ulcerative colitis, and later primary sclerosing cholangitis, parasitic diseases and choledochal cysts should be considered. In both cases, type I choledochal cysts were detected as a risk factor. Therefore, any patient with a history of a choledochal cyst is a candidate for life-long follow-up. The incidence of malignant transformation is reported as 2.5?26% (21). Cholangiocarcinoma is the second most common primary hepatic malignancy after hepatocellular cancer. Cholangiocarcinoma accounts for approximately 10-25% of all hepatobiliary malignancies. The risk of cholangiocarcinoma increases with age. The malignant change occurs mainly within the choledochal cyst, but may occur in the gallbladder, pancreatic duct, or intrahepatic bile ducts (22). The risk of cholangiocarcinoma remains high when an internal drainage procedure has been performed and the cyst has been partially resected or left unresected (15). Nodular wall thickening and/or an enhancing mass in a choledochal cyst are highly suspicious of malignant change (23,24). In these high-risk patients, fluorodeoxyglucose positron emission tomography/CT (FDG PET/ CT) may detect early tumors and reveal unsuspected distant metastases, and thus impact management (25). The typical malignancy is adenocarcinoma of the bile duct or gallbladder, and less commonly squamous cell carcinoma (26-28). Results of the pathological examinations in our cases reported adenocarcinoma on choledochal cysts. Cholangiocarcinoma is classified in accordance with the location of the primary lesion, as intrahepatic, hilar, and distal (29). Surgery and radiation therapy are the two most common treatments for cholangiocarcinoma. Palliative resections and aggressive surgical approach in the presence of regional positive lymph nodes have a relevant beneficial impact on the outcome of patients with distal and hilar cholangiocarcinoma. Cholecystectomy and Roux-en-Y choledochojejunostomy and non-surgical stenting are the first choices of palliative biliary drainage for patients with hilar cholangiocarcinoma, and for those with distal cholangiocarcinoma and short life expectancy. In both our cases with lymph invasion, cholecystectomy and Roux-en-Y choledochojejunostomy were applied. The patients were scheduled for chemoradiotherapy later. The prognosis for patients with cholangiocarcinoma arising in choledochal cysts is as grim as that for cholangiocarcinoma in general, with a median survival reported in the range of 6-21 months (30). Our patients in this study died one and three years, respectively, after the diagnosis. In conclusion, choledochal cysts are rare cystic transformations of the biliary tree. The morbidities associated with choledochal cysts depend on the age of the patient at the time of presentation. Children may develop pancreatitis and cholangitis, whereas adults may develop severe complications, such as cholangiocarcinoma, cirrhosis, and portal hypertension. Early diagnosis and treatment of the disease in such cases would prevent cholangiocarcinoma and reduce the high mortality rate.

Choledochal cysts are considered to be rare biliary tract disorders with a high mortality rate due to their late diagnosis. They are defined as congenital anomalies of the biliary tract, characterized by varying degree of cystic dilatation in various segments of the biliary tract, with extrahepatic or intrahepatic divisions (6). Our cases are among the rare examples of choledochal cysts with cholangiocarcinoma resulting in the deaths of the patients due to the late symptoms and treatment, which confirm the findings of the earlier literature. This report intends to document these examples and highlight the importance of early diagnosis and treatment. Regarding the frequency of choledochal cysts, the disease is observed in about 1 in 15,000 live births in Western countries, while the ratio is as high as 1 in 1000 live births in Japan (7). Unfortunately, the ratio of the disease is not extensively reported in Turkey. These two cases in our hospital were seen between 2006 and 2012. The literature indicates that the disease is typically more common among women, but there has been an increase recently in the number of male patients. Our study included one male and one female. Extrahepatic bile duct cysts were first classified by Alenso-Lej et al. in 1959, and revised by Todani et al., who described a system of classification of these cysts into five discrete types (Table 2). The most common are types I and IVA, whereas types II and V are generally rare (8,9). The more common type I and type IVA cysts are associated with an abnormal pancreaticobiliary duct junction, and a long common channel, as well as mixing of pancreatic and biliary juice, leading to mucosal breakdown and dilatation. Type I cysts relate to an abnormal arrangement of the pancreatobiliary ducts, also known as ?common channel,? which is seen in up to 92% of the patients with choledochal cysts. This can present in childhood with high grade reflux or later in adulthood with low grade reflux (10-12). Our cases both belong to type I. Choledochal cysts can be present at any age, and both the pediatric and adult populations presented most commonly with abdominal pain, nausea, vomiting, and jaundice (13). The type of symptoms depends largely on the age at presentation. Abdominal pain has been reported to be the most frequent symptom at presentation and is the main symptom in adults, whereas jaundice is reportedly the main presenting symptom in infants (14). It should be noted that both of the patients in this study were diagnosed with cholangiocarcinoma after their admission to the hospital with complaints of abdominal pain and weight loss, yet neither of them showed previous symptoms like abdominal pain or jaundice that would indicate choledochal cysts. Once a preliminary diagnosis is made using ultrasound (US) scanning, other supportive studies may be ordered, including abdominal computed tomography (CT) scans, magnetic resonance imaging (MRI) studies, or MRCP examinations. US has been the imaging modality of choice in children, whereas ERCP was used most commonly in adults. Percutaneous liver biopsy is contraindicated because of the risks of biliary injury and peritonitis (11,15,16). Treatment of choledochal cysts is complete surgical excision of the cyst mucosa, with a Roux-en-Y choledochojejunostomy proximal to the most distal lesion (17). Each of these drainage techniques retained the wall of the cyst with its abnormal mucosa. Poor drainage leading to stasis and persistent cyst inflammation resulted in stricture formation, biliary lithiasis, and an increased risk of malignant evolution within the cyst wall (18). Clinically, the common complications of congenital choledochal cyst were recurrent cholangitis, recurrent pancreatitis, rupture, stone formation, and malignant transformation (19,20). Of these, the most serious complication is malignant transformation. Both cases indicated no complication or clinical complaints before the development of the cholangiocarcinoma related to choledochal cysts. Although the disease is typically observed in the 5th-7th decades, cases in this study were in their forties. For cholangiocarcinoma patients diagnosed at an early age, primarily ulcerative colitis, and later primary sclerosing cholangitis, parasitic diseases and choledochal cysts should be considered. In both cases, type I choledochal cysts were detected as a risk factor. Therefore, any patient with a history of a choledochal cyst is a candidate for life-long follow-up. The incidence of malignant transformation is reported as 2.5?26% (21). Cholangiocarcinoma is the second most common primary hepatic malignancy after hepatocellular cancer. Cholangiocarcinoma accounts for approximately 10-25% of all hepatobiliary malignancies. The risk of cholangiocarcinoma increases with age. The malignant change occurs mainly within the choledochal cyst, but may occur in the gallbladder, pancreatic duct, or intrahepatic bile ducts (22). The risk of cholangiocarcinoma remains high when an internal drainage procedure has been performed and the cyst has been partially resected or left unresected (15). Nodular wall thickening and/or an enhancing mass in a choledochal cyst are highly suspicious of malignant change (23,24). In these high-risk patients, fluorodeoxyglucose positron emission tomography/CT (FDG PET/ CT) may detect early tumors and reveal unsuspected distant metastases, and thus impact management (25). The typical malignancy is adenocarcinoma of the bile duct or gallbladder, and less commonly squamous cell carcinoma (26-28). Results of the pathological examinations in our cases reported adenocarcinoma on choledochal cysts. Cholangiocarcinoma is classified in accordance with the location of the primary lesion, as intrahepatic, hilar, and distal (29). Surgery and radiation therapy are the two most common treatments for cholangiocarcinoma. Palliative resections and aggressive surgical approach in the presence of regional positive lymph nodes have a relevant beneficial impact on the outcome of patients with distal and hilar cholangiocarcinoma. Cholecystectomy and Roux-en-Y choledochojejunostomy and non-surgical stenting are the first choices of palliative biliary drainage for patients with hilar cholangiocarcinoma, and for those with distal cholangiocarcinoma and short life expectancy. In both our cases with lymph invasion, cholecystectomy and Roux-en-Y choledochojejunostomy were applied. The patients were scheduled for chemoradiotherapy later. The prognosis for patients with cholangiocarcinoma arising in choledochal cysts is as grim as that for cholangiocarcinoma in general, with a median survival reported in the range of 6-21 months (30). Our patients in this study died one and three years, respectively, after the diagnosis. In conclusion, choledochal cysts are rare cystic transformations of the biliary tree. The morbidities associated with choledochal cysts depend on the age of the patient at the time of presentation. Children may develop pancreatitis and cholangitis, whereas adults may develop severe complications, such as cholangiocarcinoma, cirrhosis, and portal hypertension. Early diagnosis and treatment of the disease in such cases would prevent cholangiocarcinoma and reduce the high mortality rate.

1. Mahendra SB, Hasmukh BV, Venugopal HG. Choledochal cysts: a review of literature. Saudi J Gastroenterol 2012;18:230-6.