Med Oncol (2014) 31:274 DOI 10.1007/s12032-014-0274-3
ORIGINAL PAPER
Diagnosis and treatment of intrahepatic biliary cystadenoma: experience with 14 cases in a single center Kewei Wang • Fanmin Kong • Ming Dong Jianping Zhou • Yuji Li
•
Received: 20 August 2014 / Accepted: 26 September 2014 / Published online: 7 October 2014 Ó Springer Science+Business Media New York 2014
Abstract Intrahepatic biliary cystadenoma (IHBCA) is a rare type of liver tumor. There are no specific diagnostic methods for IHBCA, so its preoperative diagnostic rate is still fairly low. The aims of this study were to evaluate the clinical manifestations, diagnosis, and treatment of IHBCA. We retrospectively analyzed data from 14 patients treated in our hospital from January 2004 to April 2014. Eleven patients (78.6 %) were female, and the average age was 48.0 years (range 16–77 years). The most common clinical symptoms were abdominal discomfort (i.e., abdominal pain), reported in seven cases (50 %), and fullness after eating, reported in two cases (14.3 %). Jaundice was a less common symptom reported in one case (7.1 %). Four patients (28.6 %) were asymptomatic. Enhanced computed tomography (CT) scan showed multilocular or internal septations in 11 cases (78.6 %) and papillary projections or mural nodules on the cyst wall in one case (7.1 %). After injection of a contrast agent, the cyst walls or septations were slightly enhanced in nine cases (64.3 %). All 14 patients underwent surgical resection. Only one case showed recurrence (2 years postoperatively); the remaining 13 patients were recurrence-free. Intrahepatic biliary cystadenoma often occurs in middleaged women. The main clinical symptoms are abdominal fullness with a sense of pain and jaundice. Enhanced CT is the main preoperative diagnostic method. Radical resection
K. Wang F. Kong M. Dong (&) J. Zhou Y. Li Department of Gastrointestinal Surgery, The First Affiliated Hospital of China Medical University, Shenyang 110001, Liaoning, China e-mail: [email protected]
is the best treatment for IHBCA and can effectively prevent recurrence. Keywords Cystadenoma Bile ducts Treatment Recurrence
Introduction Intrahepatic biliary cystadenoma (IHBCA) is a rare type of liver tumor. It accounts for less than 5 % of all cystic liver lesions [1, 2] and occurs most frequently in women older than 50 years. The course of IHBCA ranges from a few months to several years. With the current developments in radiological imaging, disease detection has significantly increased. However, as there are no specific diagnostic methods for IHBCA, its preoperative diagnostic rate is still fairly low. It is easily misdiagnosed and treatment is often delayed. With the goal of evaluating the clinical manifestations, diagnosis, and treatment of IHBCA, we performed a retrospective review of 14 consecutive IHBCA patients treated in our hospital from January 2004 to April 2014.
Materials and methods The medical records of 16 patients diagnosed with IHBCA and treated in our hospital between January 2004 and April 2014 were reviewed. Two patients were lost to follow-up. The remaining 14 patients’ clinical data were collected for analysis. Clinical data included sex, age, clinical manifestation, serum tumor markers, and radiological findings. This study was approved by the Ethics Committee of China Medical University, and all patients gave their informed consent prior to inclusion in the study.
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Table 1 Characteristics of the patients Total number of patients
Table 2 Treatment and follow-up date 14
Sex
Surgery Hepatic left lateral lobectomy
7 (50 %)
Male
3 (21.4 %)
Left hepatectomy
2 (14.3 %)
Female
11 (78.6 %)
Partial right hepatic resection
4 (28.6 %)
Nonanatomic hepatic resection
1 (7.1 %)
Age (years) Median
48
Range
16–77
Symptoms Abdominal pain
7 (50 %)
Complications Biliary fistula
1 (7.1 %)
Abdominal infection
1 (7.1 %)
Follow-up time (months)
Fullness after eating
2 (14.3 %)
Median
54
Jaundice
1 (7.1 %)
Range
4–112
Tumor location
Recurrence
Left lobe
9 (64.3 %)
Yes
1 (7.1 %)
Right lobe
4 (28.6 %)
No
13 (92.9 %)
Caudate lobe Tumor sizes (cm)
1 (7.1 %)
Median
10.43 ± 6.28
Range
2–24
were present in 11 cases (78.6 %), and papillary projections or mural nodules on the cyst wall were present in one case (7.1 %). After injection of a contrast agent, the cyst walls or septations were slightly enhanced in nine cases (64.3 %).
Results
Treatment and complications
Clinical characteristics
All patients underwent surgical treatment, which consisted of left lateral hepatic lobectomy in seven cases, left hepatectomy in two cases, partial right hepatic resection in four cases, and nonanatomic resection in one case. One patient experienced ascites due to hypoalbuminemia along with a secondary abdominal infection after surgery. This patient was cured after adequate drainage, anti-inflammatories, and other nonsurgical treatment. Biliary fistula occurred in one case but was cured by drainage without a secondary operation. No abdominal bleeding, liver failure, other severe complications, or death occurred (Table 2).
Eleven patients (78.6 %) were female and three (21.4 %) were male. Their mean age was 48 years (range 16–77 years). The most common symptoms were abdominal discomfort (i.e., abdominal pain), reported in seven patients (50 %), and fullness after eating, reported in two patients (14.3 %). Jaundice was a less common symptom reported in one patient (7.1 %). Four patients were asymptomatic (28.6 %). On physical examination, a palpable mass was identified in the right upper quadrant or under the xiphoid in three cases (21.4 %), and abdominal tenderness was present in five cases (35.7 %). Physical examination was negative in the other six cases (42.9 %). Twelve patients underwent serum tumor marker examination, including carbohydrate antigen (CA19-9) and carcinoembryonic antigen (CEA). Serum CA19-9 concentration was elevated in four of the 12 cases (33.3 %), and serum CEA concentration was elevated in two of the 12 cases (16.7 %). On preoperative radiological examination, the tumor was located in the left lobe of the liver in nine cases (64.3 %), the right lobe of the liver in four cases (28.6 %), and the caudate lobe in one case (7.1 %). The mean maximum IHBCA lesion diameter was 10.43 ± 6.28 cm, with a range of 2–24 cm (Table 1). All patients underwent an enhanced CT scan; multilocular or internal septations
123
Pathological examination Histopathologic examination revealed IHBCA in 13 cases; the remaining case was considered to be a cystadenoma that had undergone malignant transformation because the epithelial cells of the cyst showed a high degree of atypia and infiltrative growth. The specimens showed clear tumor boundaries, multiple cysts, and septations between two cysts. The color of the cystic fluid varied; it was yellowish in seven cases, brown in four cases, and colorless in three cases. Intraoperatively, the common bile duct of the patient with jaundice was found to be filled with jelly-like mucus. Ovarian-like mesenchymal stroma was observed in seven cases.
Med Oncol (2014) 31:274
Follow-up data The patients were followed for a median of 54 months (range 4–112 months). Only the case with malignant transformation showed recurrence, which occurred 2 years after the initial operation. After a secondary operation, the patient was cured and has survived for 37 months postoperatively to date. The other 13 cases were recurrencefree.
Discussion Biliary cystadenoma mainly occurs in the intrahepatic bile duct and only rarely in the extrahepatic bile ducts or gallbladder [3, 4]. Its cyst walls are covered by cubic or columnar epithelial cells with secretory function. Intrahepatic biliary cystadenoma can be divided into mucinous and serous subtypes. More than 80 % of cases occur in women, and more than 80 % of patients are older than 30 years [5]; the most common age at onset is approximately 50 years [6]. In our study, 11 of the patients were female, making up 78.6 % of the total. The mean age was 48 years old, with a range of 16–77 years. At present, the youngest reported age at onset is 1.5 years [7]. Intrahepatic biliary cystadenoma grows slowly, but it has a tendency toward malignant transformation; its malignant transformation rate is as high as 30 %. The origin of the tumor tissue and cause of the disease are not yet clear, and there are several possibilities according to the literature [8]: IHBCA may arise from ectopic embryonic gallbladder tissue, from a Luschka bile duct created by embryonic developmental abnormalities, or from ectopic ovarian tissue, and its development may be related to oral contraceptive use. Symptoms of IHBCA are usually atypical and include abdominal pain, a palpable mass, a sense of fullness, nausea, and occasionally jaundice or other symptoms depending on the location of the tumor [9]. In some cases, jelly-like mucus secreted by the tumor may block the common bile duct and lead to obstructive jaundice. Jelly-like mucus may even flow into the gastrointestinal tract through a biliary-duodenal fistula caused by tumor invasion [10]. Serum tumor markers with good sensitivity and specificity are considered useful diagnostic tools for neoplasms, but until now, none have been specifically assigned to IHBCA. Carbohydrate antigen 19-9 (CA19-9) has sometimes been regarded as a tumor marker for IHBCA because it has been shown to be elevated in patients with IHBCA [11, 12] and to decrease after surgery [13]. However, patients with IHBCA present with normal serum levels of CA19-9 in many cases [14]. In our study, only four of the 12 cases with measured CA19-9 levels (33.3 %) had
Page 3 of 4 274
elevated serum concentrations of CA19-9 and two of the 12 cases (16.7 %) had elevated serum concentrations of CEA; the other cases had normal levels. It has been reported that the CA19-9 level of the cystic fluid might be of diagnostic use [15]. However, definite diagnostic criteria have not been established for CA19-9 levels in cystic fluid; the published data are largely limited to reports of increased levels in small numbers of IHBCA patients, and statistically robust comparisons with CA19-9 levels in simple cysts are lacking. Koffron et al. [16] compared the levels of CEA and CA19-9 in the cystic fluid of 22 IHBCA patients with the levels found in four patients with simple cysts and four patients with polycystic liver disease. All eight control cases had normal levels; in contrast, CA19-9 was markedly increased in all IHBCA patients, and there were mild to marked increases in CEA as well. These authors concluded that cystic fluid levels of CA19-9 and CEA were more useful than serum levels. However, other studies have not found cystic fluid levels of CA19-9 and CEA to be useful in the differential diagnosis of biliary cystadenoma (BCA) and hepatic simple cysts (HSCs) [17]. The role of cystic fluid tumor marker levels has not yet been established by a study with a large sample size. The diagnosis of IHBCA mainly depends on radiological findings and typically involves the use of ultrasound, CT, or MRI. On CT, IHBCA is typically characterized as a low-density cystic mass in the liver with single or multicystic change, a thin wall, and a CT enhancement value less than 30 HU. There may be septations between two cysts, and the CT enhancement value may differ between septations. The septations or cyst walls may exhibit calcification. On enhanced CT scan, the cyst walls or septations demonstrate enhancement [18]. Buelow et al. [19] reported that the tumor components or septations enhanced as early as the arterial phase and demonstrated continued enhancement in the portal venous phase or delayed phase. In our study, all of the patients underwent enhanced CT scan; nine lesions were located in the left hepatic lobe (64.3 %), four in the right hepatic lobe (28.6 %), and one in the caudate lobe (7.1 %). The left lobe was a much more common site than the right lobe, which is in accordance with the reports by Regev et al. [20] and Wang et al. [21]. Multilocular or internal septations were observed in 11 cases (78.6 %). After injection of a contrast agent, the cyst walls or septations were slightly enhanced in nine cases (64.3 %). Computed tomography cannot fully distinguish intrahepatic biliary cystadenocarcinoma from intrahepatic biliary cystadenoma, but thickening or calcification of septations and mural nodules or papillae on cyst walls raise the consideration for intrahepatic biliary cystadenocarcinoma. In this study, only one patient’s CT scan showed mural nodules on cyst walls with coarse calcifications and a different degree of enhancement. The postoperative
123
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Med Oncol (2014) 31:274
pathological diagnosis was local malignant transformation of a cystadenoma in this case. Intrahepatic biliary cystadenoma is a precancerous cystadenocarcinoma lesion, so radical resection is recommended when this disease is suspected [22–24]. All 14 patients in this study underwent complete surgical resection; the resection margins were at least 2 cm from the tumor. When recurrences develop following the surgical resection of IHBCA, a secondary surgical resection is necessary. In this study, only the case with malignant cystadenoma transformation showed recurrence, which occurred 2 years after the initial operation. After a secondary operation, the patient was cured and has survived for 37 months postoperatively to date. The other 13 cases were recurrence-free. Recently, good treatment effects were reported with laparoscopic cystectomy [16, 25]. With incomplete resections, such as fine needle aspiration, fenestration, internal drainage, or partial cyst wall resection, recurrence rates as high as 90 % have been reported [3, 4]. In contrast, only 10 % of patients developed recurrences after radical IHBCA resection in a previous study [14]. Therefore, radical tumor resection is the best treatment for IHBCA and can effectively prevent its recurrence.
Conclusion Intrahepatic biliary cystadenoma often occurs in middleaged women. The main clinical symptoms are abdominal fullness with a sense of pain and jaundice. Enhanced CT is the main preoperative diagnostic method. Radical IHBCA resection is the best treatment and can effectively prevent recurrence. Conflict of interest
None.
References 1. Kazama S, Hiramatsu T, Kuriyama S, et al. Giant intrahepatic biliary cystadenoma in a male: a case report, immunohistopathological analysis, and review of the literature. Dig Dis Sci. 2005;50:1384–9. 2. Teoh AY, Ng SS, Lee KF, et al. Biliary cystadenoma and other complicated cystic lesions of the liver: diagnostic and therapeutic challenges. World J Surg. 2006;30:1560–6. 3. Florman SS, Slakey DP. Giant biliary cystadenoma: case report and literature review. Am Surg. 2001;67:727–32. 4. Rooney TB, Schofer JM, Stanley MD, Banks SL. Biliary cystadenoma of the gallbladder. AJR Am J Roentgenol. 2005;185: 1571–2.
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5. Pojchamarnwiputh S, Na Chiangmai W, Chotirosniramit A, et al. Computed tomography of biliary cystadenoma and biliary cystadenocarcinoma. Singap Med J. 2008;49:392–6. 6. Del Poggio P, Buonocore M. Cystic tumors of the liver: a practical approach. World J Gastroenterol. 2008;14:3616–20. 7. Senyu¨z OF, Numan F, Erog˘lu E, et al. Hepatobiliary mucinous cystadenoma in a child. J Pediatr Surg. 2004;39:E6–8. 8. Vogt DP, Henderson JM, Chmielewski E. Cystadenoma and cystadenocarcinoma of the liver: a single center experience. J Am Coll Surg. 2005;200:727–33. 9. Preetha M, Chung AY, Lim-Tan SK, et al. Intrahepatic biliary cystadenoma presenting with obstructive jaundice. Asian J Surg. 2004;27:243–5. 10. Ohtsubo K, Ohta H, Sakai J, et al. Mucin-producing biliary papillomatosis associated with gastrobiliary fistula. J Gastroenterol. 1999;34:141–4. 11. Thomas JA, Scriven MW, Puntis MC, et al. Elevated serum CA 19-9 levels in hepatobiliary cystadenoma with mesenchymal stroma. Two case reports with immunohistochemical confirmation. Cancer. 1992;70:1841–6. 12. Delis SG, Touloumis Z, Bakoyiannis A, et al. Intrahepatic biliary cystadenoma: a need for radical resection. Eur J Gastroenterol Hepatol. 2008;20:10–4. 13. Schoonbroodt D, Horsmans Y, Gigot JF, et al. Biliary cystadenoma of the liver with elevated CA19-9. Liver. 1994;14:320–2. 14. Thomas KT, Welch D, Trueblood A, et al. Effective treatment of biliary cystadenoma. Ann Surg. 2005;241:769–75. 15. Horsmans Y, Laka A, Gigot JF, et al. Serum and cystic fluid CA 19-9 determinations as a diagnostic help in liver cysts of uncertain nature. Liver. 1996;16:255–7. 16. Koffron A, Ferrario M, Rao S, et al. Intrahepatic biliary cystadenoma (IBC): role of cyst fluid analysis and surgical management in the laparoscopic era. Surgery. 2004;136:926–36. 17. Choi HK, Lee JK, Lee KH, et al. Differential diagnosis for intrahepatic biliary cystadenoma and hepatic simple cyst significance of cystic fluid analysis and radiologic findings. J Clin Gastroenterol. 2010;44:289–93. 18. Choi BI, Lim JH, Han MC, et al. Biliary cystadenoma and cystadenocarcinoma: CT and sonographic findings. Radiology. 1989;171:57–61. 19. Buetow PC, Buck JL, Pantongrag-Brown L, et al. Biliary cystadenoma and cystadenocarcinoma: clinical-imaging-pathologic correlation with emphasis on the importance of ovarian stroma. Radiology. 1995;196:805–10. 20. Regev A, Reddy KR, Berho M, et al. Large cystic lesions of the liver in adults: 15-year experience in a tertiary center. J Am Coll Surg. 2001;193:36–45. 21. Wang C, Miao R, Liu H, et al. Intrahepatic biliary cystadenoma and cystadenocarcinoma: an experience of 30 cases. Dig Liver Dis. 2012;44:426–31. 22. Limongelli P, Pai M, Damrah O, et al. Cystic tumors of the biliary tract: a complete excision is crucial. Int Surg. 2009;94:136–40. 23. Wu JM, Wu YM, Ho MC, et al. Surgical treatment of biliary cystadenomas. Int Surg. 2008;93:373–6. 24. Zhou J, Dong M, Kong F, et al. Giant mucinous biliary cystadenoma: a case report. Hepatobiliary Pancreat Dis Int. 2007;6:101–3. 25. Veroux M, Fiamingo P, Cillo U, et al. Cystadenoma and laparoscopic surgery for hepatic cystic disease: a need for laparotomy? Surg Endosc. 2005;19:1077–81.
ORIGINAL PAPER
Diagnosis and treatment of intrahepatic biliary cystadenoma: experience with 14 cases in a single center Kewei Wang • Fanmin Kong • Ming Dong Jianping Zhou • Yuji Li
•
Received: 20 August 2014 / Accepted: 26 September 2014 / Published online: 7 October 2014 Ó Springer Science+Business Media New York 2014
Abstract Intrahepatic biliary cystadenoma (IHBCA) is a rare type of liver tumor. There are no specific diagnostic methods for IHBCA, so its preoperative diagnostic rate is still fairly low. The aims of this study were to evaluate the clinical manifestations, diagnosis, and treatment of IHBCA. We retrospectively analyzed data from 14 patients treated in our hospital from January 2004 to April 2014. Eleven patients (78.6 %) were female, and the average age was 48.0 years (range 16–77 years). The most common clinical symptoms were abdominal discomfort (i.e., abdominal pain), reported in seven cases (50 %), and fullness after eating, reported in two cases (14.3 %). Jaundice was a less common symptom reported in one case (7.1 %). Four patients (28.6 %) were asymptomatic. Enhanced computed tomography (CT) scan showed multilocular or internal septations in 11 cases (78.6 %) and papillary projections or mural nodules on the cyst wall in one case (7.1 %). After injection of a contrast agent, the cyst walls or septations were slightly enhanced in nine cases (64.3 %). All 14 patients underwent surgical resection. Only one case showed recurrence (2 years postoperatively); the remaining 13 patients were recurrence-free. Intrahepatic biliary cystadenoma often occurs in middleaged women. The main clinical symptoms are abdominal fullness with a sense of pain and jaundice. Enhanced CT is the main preoperative diagnostic method. Radical resection
K. Wang F. Kong M. Dong (&) J. Zhou Y. Li Department of Gastrointestinal Surgery, The First Affiliated Hospital of China Medical University, Shenyang 110001, Liaoning, China e-mail: [email protected]
is the best treatment for IHBCA and can effectively prevent recurrence. Keywords Cystadenoma Bile ducts Treatment Recurrence
Introduction Intrahepatic biliary cystadenoma (IHBCA) is a rare type of liver tumor. It accounts for less than 5 % of all cystic liver lesions [1, 2] and occurs most frequently in women older than 50 years. The course of IHBCA ranges from a few months to several years. With the current developments in radiological imaging, disease detection has significantly increased. However, as there are no specific diagnostic methods for IHBCA, its preoperative diagnostic rate is still fairly low. It is easily misdiagnosed and treatment is often delayed. With the goal of evaluating the clinical manifestations, diagnosis, and treatment of IHBCA, we performed a retrospective review of 14 consecutive IHBCA patients treated in our hospital from January 2004 to April 2014.
Materials and methods The medical records of 16 patients diagnosed with IHBCA and treated in our hospital between January 2004 and April 2014 were reviewed. Two patients were lost to follow-up. The remaining 14 patients’ clinical data were collected for analysis. Clinical data included sex, age, clinical manifestation, serum tumor markers, and radiological findings. This study was approved by the Ethics Committee of China Medical University, and all patients gave their informed consent prior to inclusion in the study.
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Table 1 Characteristics of the patients Total number of patients
Table 2 Treatment and follow-up date 14
Sex
Surgery Hepatic left lateral lobectomy
7 (50 %)
Male
3 (21.4 %)
Left hepatectomy
2 (14.3 %)
Female
11 (78.6 %)
Partial right hepatic resection
4 (28.6 %)
Nonanatomic hepatic resection
1 (7.1 %)
Age (years) Median
48
Range
16–77
Symptoms Abdominal pain
7 (50 %)
Complications Biliary fistula
1 (7.1 %)
Abdominal infection
1 (7.1 %)
Follow-up time (months)
Fullness after eating
2 (14.3 %)
Median
54
Jaundice
1 (7.1 %)
Range
4–112
Tumor location
Recurrence
Left lobe
9 (64.3 %)
Yes
1 (7.1 %)
Right lobe
4 (28.6 %)
No
13 (92.9 %)
Caudate lobe Tumor sizes (cm)
1 (7.1 %)
Median
10.43 ± 6.28
Range
2–24
were present in 11 cases (78.6 %), and papillary projections or mural nodules on the cyst wall were present in one case (7.1 %). After injection of a contrast agent, the cyst walls or septations were slightly enhanced in nine cases (64.3 %).
Results
Treatment and complications
Clinical characteristics
All patients underwent surgical treatment, which consisted of left lateral hepatic lobectomy in seven cases, left hepatectomy in two cases, partial right hepatic resection in four cases, and nonanatomic resection in one case. One patient experienced ascites due to hypoalbuminemia along with a secondary abdominal infection after surgery. This patient was cured after adequate drainage, anti-inflammatories, and other nonsurgical treatment. Biliary fistula occurred in one case but was cured by drainage without a secondary operation. No abdominal bleeding, liver failure, other severe complications, or death occurred (Table 2).
Eleven patients (78.6 %) were female and three (21.4 %) were male. Their mean age was 48 years (range 16–77 years). The most common symptoms were abdominal discomfort (i.e., abdominal pain), reported in seven patients (50 %), and fullness after eating, reported in two patients (14.3 %). Jaundice was a less common symptom reported in one patient (7.1 %). Four patients were asymptomatic (28.6 %). On physical examination, a palpable mass was identified in the right upper quadrant or under the xiphoid in three cases (21.4 %), and abdominal tenderness was present in five cases (35.7 %). Physical examination was negative in the other six cases (42.9 %). Twelve patients underwent serum tumor marker examination, including carbohydrate antigen (CA19-9) and carcinoembryonic antigen (CEA). Serum CA19-9 concentration was elevated in four of the 12 cases (33.3 %), and serum CEA concentration was elevated in two of the 12 cases (16.7 %). On preoperative radiological examination, the tumor was located in the left lobe of the liver in nine cases (64.3 %), the right lobe of the liver in four cases (28.6 %), and the caudate lobe in one case (7.1 %). The mean maximum IHBCA lesion diameter was 10.43 ± 6.28 cm, with a range of 2–24 cm (Table 1). All patients underwent an enhanced CT scan; multilocular or internal septations
123
Pathological examination Histopathologic examination revealed IHBCA in 13 cases; the remaining case was considered to be a cystadenoma that had undergone malignant transformation because the epithelial cells of the cyst showed a high degree of atypia and infiltrative growth. The specimens showed clear tumor boundaries, multiple cysts, and septations between two cysts. The color of the cystic fluid varied; it was yellowish in seven cases, brown in four cases, and colorless in three cases. Intraoperatively, the common bile duct of the patient with jaundice was found to be filled with jelly-like mucus. Ovarian-like mesenchymal stroma was observed in seven cases.
Med Oncol (2014) 31:274
Follow-up data The patients were followed for a median of 54 months (range 4–112 months). Only the case with malignant transformation showed recurrence, which occurred 2 years after the initial operation. After a secondary operation, the patient was cured and has survived for 37 months postoperatively to date. The other 13 cases were recurrencefree.
Discussion Biliary cystadenoma mainly occurs in the intrahepatic bile duct and only rarely in the extrahepatic bile ducts or gallbladder [3, 4]. Its cyst walls are covered by cubic or columnar epithelial cells with secretory function. Intrahepatic biliary cystadenoma can be divided into mucinous and serous subtypes. More than 80 % of cases occur in women, and more than 80 % of patients are older than 30 years [5]; the most common age at onset is approximately 50 years [6]. In our study, 11 of the patients were female, making up 78.6 % of the total. The mean age was 48 years old, with a range of 16–77 years. At present, the youngest reported age at onset is 1.5 years [7]. Intrahepatic biliary cystadenoma grows slowly, but it has a tendency toward malignant transformation; its malignant transformation rate is as high as 30 %. The origin of the tumor tissue and cause of the disease are not yet clear, and there are several possibilities according to the literature [8]: IHBCA may arise from ectopic embryonic gallbladder tissue, from a Luschka bile duct created by embryonic developmental abnormalities, or from ectopic ovarian tissue, and its development may be related to oral contraceptive use. Symptoms of IHBCA are usually atypical and include abdominal pain, a palpable mass, a sense of fullness, nausea, and occasionally jaundice or other symptoms depending on the location of the tumor [9]. In some cases, jelly-like mucus secreted by the tumor may block the common bile duct and lead to obstructive jaundice. Jelly-like mucus may even flow into the gastrointestinal tract through a biliary-duodenal fistula caused by tumor invasion [10]. Serum tumor markers with good sensitivity and specificity are considered useful diagnostic tools for neoplasms, but until now, none have been specifically assigned to IHBCA. Carbohydrate antigen 19-9 (CA19-9) has sometimes been regarded as a tumor marker for IHBCA because it has been shown to be elevated in patients with IHBCA [11, 12] and to decrease after surgery [13]. However, patients with IHBCA present with normal serum levels of CA19-9 in many cases [14]. In our study, only four of the 12 cases with measured CA19-9 levels (33.3 %) had
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elevated serum concentrations of CA19-9 and two of the 12 cases (16.7 %) had elevated serum concentrations of CEA; the other cases had normal levels. It has been reported that the CA19-9 level of the cystic fluid might be of diagnostic use [15]. However, definite diagnostic criteria have not been established for CA19-9 levels in cystic fluid; the published data are largely limited to reports of increased levels in small numbers of IHBCA patients, and statistically robust comparisons with CA19-9 levels in simple cysts are lacking. Koffron et al. [16] compared the levels of CEA and CA19-9 in the cystic fluid of 22 IHBCA patients with the levels found in four patients with simple cysts and four patients with polycystic liver disease. All eight control cases had normal levels; in contrast, CA19-9 was markedly increased in all IHBCA patients, and there were mild to marked increases in CEA as well. These authors concluded that cystic fluid levels of CA19-9 and CEA were more useful than serum levels. However, other studies have not found cystic fluid levels of CA19-9 and CEA to be useful in the differential diagnosis of biliary cystadenoma (BCA) and hepatic simple cysts (HSCs) [17]. The role of cystic fluid tumor marker levels has not yet been established by a study with a large sample size. The diagnosis of IHBCA mainly depends on radiological findings and typically involves the use of ultrasound, CT, or MRI. On CT, IHBCA is typically characterized as a low-density cystic mass in the liver with single or multicystic change, a thin wall, and a CT enhancement value less than 30 HU. There may be septations between two cysts, and the CT enhancement value may differ between septations. The septations or cyst walls may exhibit calcification. On enhanced CT scan, the cyst walls or septations demonstrate enhancement [18]. Buelow et al. [19] reported that the tumor components or septations enhanced as early as the arterial phase and demonstrated continued enhancement in the portal venous phase or delayed phase. In our study, all of the patients underwent enhanced CT scan; nine lesions were located in the left hepatic lobe (64.3 %), four in the right hepatic lobe (28.6 %), and one in the caudate lobe (7.1 %). The left lobe was a much more common site than the right lobe, which is in accordance with the reports by Regev et al. [20] and Wang et al. [21]. Multilocular or internal septations were observed in 11 cases (78.6 %). After injection of a contrast agent, the cyst walls or septations were slightly enhanced in nine cases (64.3 %). Computed tomography cannot fully distinguish intrahepatic biliary cystadenocarcinoma from intrahepatic biliary cystadenoma, but thickening or calcification of septations and mural nodules or papillae on cyst walls raise the consideration for intrahepatic biliary cystadenocarcinoma. In this study, only one patient’s CT scan showed mural nodules on cyst walls with coarse calcifications and a different degree of enhancement. The postoperative
123
274 Page 4 of 4
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pathological diagnosis was local malignant transformation of a cystadenoma in this case. Intrahepatic biliary cystadenoma is a precancerous cystadenocarcinoma lesion, so radical resection is recommended when this disease is suspected [22–24]. All 14 patients in this study underwent complete surgical resection; the resection margins were at least 2 cm from the tumor. When recurrences develop following the surgical resection of IHBCA, a secondary surgical resection is necessary. In this study, only the case with malignant cystadenoma transformation showed recurrence, which occurred 2 years after the initial operation. After a secondary operation, the patient was cured and has survived for 37 months postoperatively to date. The other 13 cases were recurrence-free. Recently, good treatment effects were reported with laparoscopic cystectomy [16, 25]. With incomplete resections, such as fine needle aspiration, fenestration, internal drainage, or partial cyst wall resection, recurrence rates as high as 90 % have been reported [3, 4]. In contrast, only 10 % of patients developed recurrences after radical IHBCA resection in a previous study [14]. Therefore, radical tumor resection is the best treatment for IHBCA and can effectively prevent its recurrence.
Conclusion Intrahepatic biliary cystadenoma often occurs in middleaged women. The main clinical symptoms are abdominal fullness with a sense of pain and jaundice. Enhanced CT is the main preoperative diagnostic method. Radical IHBCA resection is the best treatment and can effectively prevent recurrence. Conflict of interest
None.
References 1. Kazama S, Hiramatsu T, Kuriyama S, et al. Giant intrahepatic biliary cystadenoma in a male: a case report, immunohistopathological analysis, and review of the literature. Dig Dis Sci. 2005;50:1384–9. 2. Teoh AY, Ng SS, Lee KF, et al. Biliary cystadenoma and other complicated cystic lesions of the liver: diagnostic and therapeutic challenges. World J Surg. 2006;30:1560–6. 3. Florman SS, Slakey DP. Giant biliary cystadenoma: case report and literature review. Am Surg. 2001;67:727–32. 4. Rooney TB, Schofer JM, Stanley MD, Banks SL. Biliary cystadenoma of the gallbladder. AJR Am J Roentgenol. 2005;185: 1571–2.
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