Biliary Tree Cysts and Surgical Treatment: Outcomes in a Multicentric Study

Abstract

Background:

Biliary tree cysts (BTCs) represent an either localized or multifocal abnormal dilatation of the biliary tree, which entails an increased risk of acute cholangitis and cholangiocarcinoma (2.5%–16%). Its incidence in Western countries is ∼1/100.000–1/150.000, being more frequent in Asia (1/1.000). These cysts are usually classified according to Todani classification, which is based on site and morphology of cysts.

Patients and Methods:

This is a retrospective multicentric descriptive study of patients surgically treated for BTCs. From 2005 to 2018, 25 cases were collected between Hospital de la Santa Creu i Sant Pau (Barcelona, Spain) and Ospedale San Paolo (Savona, Italy). Clinical presentation was characterized by abdominal pain, jaundice, fever, and sometimes weight loss. Eight patients presented Todani type I, 1 patient Todani type II, 3 patients Todani III, 1 patient Todani type IV, and 12 patients Todani type V.

Results:

Among the 25 surgically treated patients, 12 patients underwent liver resection, 7 patients underwent resection of the extrahepatic biliary tree, 3 patients underwent BTC removal through a duodenotomy, 1 patient underwent resection of the extrahepatic biliary tree and liver resection, and 2 patients underwent pancreatoduodenectomy. Overall 30-day morbidity rate was 20%, and 90-day mortality was 0%. Pathologic examination confirmed diagnosis of cholangiocarcinoma in 5 patients (20%). After a median follow-up of 59 months, 20 patients are alive and in good conditions, whereas 50% of patients with cholangiocarcinoma died for disease progression.

Conclusions:

Surgical treatment for BTCs is associated with acceptable postoperative outcomes, with moderate morbidity and null mortality rates. Moreover, the risk of developing cholangiocarcinoma is still high that prompts surgical treatment once diagnosis is made.

Introduction

Biliary tree cysts (BTCs) represent a rare disease that affects the morphology of the extrahepatic and intrahepatic biliary ducts, which appear ectatic due to isolated or combined dilatations of the biliary tree.¹ They are often diagnosed in childhood (80%), but a small number of individuals are incidentally diagnosed in adult age.^1,2

This disease was first described by Vater and Ezler in 1723, and later classified into five categories by Todani et al. in 1977 according to the location of cystic dilation.³

Type I involves the entire common bile duct (CBD), type II involves the extrahepatic biliary tree with a diverticular morphology, type III involves the intraduodenal portion of CBD with cystic dilatation, type IV involves both the intrahepatic and extrahepatic biliary tree with multiple cysts, and type V (also known as Caroli disease) involves the intrahepatic biliary tree with isolated dilatations.

Owing to biliary stasis, patients with BTCs have a higher incidence of biliary disorders such as cholangitis and pancreatitis.⁴ Moreover, BTC seems to be associated with an increased risk of developing malignant lesions and is currently seen as a premalignant lesion, probably as a result of a chronic inflammation of the biliary tree.⁵ The incidence of invasive carcinoma associated with BTC is around 2.5%–16% (mostly cholangiocarcinoma, 10% gallbladder cancer).^1,6,7 For these reasons, BTC is currently an indication for surgical treatment.

The objective of this study is to analyze operative, postoperative, and long-term oncological outcomes in patients in a large series of patients with BTCs surgically treated.

Patients and Methods

This is a multicenter descriptive study of patients surgically treated for BTCs. Patients were collected in a prospective register and were reviewed retrospectively.

From 2005 to 2018, we recruited all consecutive patients who were diagnosed with BTCs at Hospital de la Santa Creu i Sant Pau (Barcelona, Spain) and Ospedale San Paolo (Savona, Italy).

Exclusion criteria were patients not surgically treated and lost follow-up cases.

The study protocol followed the ethical guidelines of the 1975 Declaration of Helsinki (as revised in Brazil 2013).

Results are reported according to the principles of Strengthening the Reporting of Observational Studies in Epidemiology.⁸

We reviewed data for all patients from medical record available on hospital databases.

Preoperatory features were collected: gender, age, body mass index, comorbidities, Todani staging based on colangio MRI images, measurement of maximum diameter of cysts, and blood tests assessing liver functionality. Intraoperative features were operative time, technical complications, blood loss, use of Pringle maneuver, use of laparoscopy, and eventual conversion.

The procedures were performed by four surgeons trained in Hepato-Pancreato-Biliary (HPB) surgery.

Postoperative complications were classified using Clavien–Dindo classification.

A standard evaluation of the surgical specimen was carried out by a trained pathologist. In patients with pathology findings of cholanciocarcinoma, adjuvant treatment was proposed.

All the patients were followed at least for 5 years. Patients were checked up to 3 months intervals during the first 2 years. Routine postoperative controls included physical examination, blood carcinoembryonic antigen and carbohydrate antigen 19-9 (CA 19-9) levels, abdominopelvic computed tomography, or magnetic resonance imaging scan.

Categorical variables were compared using chi-square test; continuous variables are presented as media ± standard deviation (SD) and were compared using t-tests. Survival outcomes were analyzed by performing Kaplan–Meier curves.

Statistical analysis was performed using SPSS 25 (SPSS, Inc., Chicago, IL).

The study was approved by the local ethics committee who deemed that formal approval was not required owing to the retrospective, observational, and anonymous nature of this study.

Results

Demographics

We summarized demographic characteristics in Table 1. A total of 25 patients were treated: 19 females (76%) and 6 males (24%). Mean age was 58 years with a range of 23–88 years.

Table 1.

Population Characteristics

	Gender	Age	Jaundice	Todani type	Symptoms	Surgery	Laparoscopic	Post-operative complications
01	F	40	Yes	I	Yes (abdominal pain)	Biliary tree resection	No	No
02	F	44	No	I	Yes (abdominal pain)	Biliary tree resection	Yes	No
03	F	71	No	I	No	Biliary tree resection	No	No
04	F	82	No	I	No	Biliary tree resection	No	Yes (Wound infection and postoperative ileus)
05	M	73	Yes	I	Yes (unpainful jaundice)	PD	No	No
06	M	36	Yes	I	Yes (abdominal pain)	PD	Yes	No
07	F	78	No	I	Yes (cholangitis)	Biliary tree resection	No	No
08	F	23	No	I	Yes (astenia, weight loss)	Biliary tree resection	Yes	No
09	F	30	Yes	II	Yes (abdominal pain)	Biliary tree resection	Yes	Yes (recovery in ICU for PE)
10	F	72	No	III	Yes (abdominal pain)	BTC resection through a duodenotomy	Yes	Yes (wound infection and postoperative ileus)
11	F	24	Yes	III	Yes (cholangitis)	BTC resection through a duodenotomy	No	No
12	F	76	No	III	No	BTC resection through a duodenotomy	Yes	No
13	F	88	No	IV	Yes (abdominal pain)	Extrahepatic biliary tree resection and liver resection	No	No
14	M	52	No	V	Yes (cholangitis)	Hepatic lobectomy	Yes	No
15	F	57	No	V	Yes (cholangitis)	Hepatic lobectomy	Yes	No
16	F	67	No	V	Yes (cholangitis)	Left hepatectomy	Yes	No
17	M	75	No	V	Yes (abdominal pain)	Hepatic lobectomy	No	Yes (wound infection and postoperative ileus)
18	F	72	No	V	Yes (weight loss and abdominal pain)	Left hepatectomy	No	No
19	F	69	No	V	Yes (abdominal pain)	Hepatic lobectomy	Yes	No
20	M	53	Yes	V	Yes (abdominal pain)	Hepatic segmentectomy	Yes	Yes (intra-abdominal abscess percutaneously drained)
21	M	64	No	V	Yes (acute pancreatitis)	Left hepatectomy	No	No
22	F	44	Yes	V	Yes (abdominal pain)	Right hepatectomy	Yes	No
23	F	69	No	V	No	Hepatic lobectomy	No	No
24	F	74	No	V	No	Hepatic lobectomy	No	No
25	F	66	No	V	Yes (weight loss and abdominal pain)	Left hepatectomy	No	No

BTCs, biliary tree cysts; PE, pulmonary embolism; PD, pancreatoduodenectomy.

Patients' cysts were categorized using Todani classification: 48% of patients presented Todani type V followed by Todani type I detected in 32% of patients (Table 1).

Majority of patients presented symptoms (80%) with a median duration of 1.47 months from beginning of symptomatology to diagnosis (range 0.06–190.06 months). The main symptomatology (48%) was upper right abdominal pain and 7 patients had jaundice (28%).

Treatment

Table 1 shows specific treatments for patients with BTCs according to Todani classification. Twelve patients underwent liver resection, 7 patients underwent resection of the extrahepatic biliary tree, 3 patients underwent BTC removal through a duodenotomy, 1 patient underwent resection of the extrahepatic biliary tree and liver resection, and 2 patients underwent pancreatoduodenectomy (Table 1).

Laparoscopic approach was used for 48% of our population (12 patients).

Outcomes

Mean length of stay was 13 days with a range of 6–39 days.

Postoperative complications (Table 1) occurred in 5 patients (20%): 3 patients had complication type II (wound infection and postoperative ileus), 1 patient had complication type IIIa (intrabdominal abscess percutaneously drained), and 1 patient had complication type IVa (acute pulmonary embolism) following Clavien–Dindo classification. Postoperative (30 days) mortality was 0%.

No significant increase in postoperative complications was observed in a given subgroup of patients according to the Todani classification.

Pathological examination showed cholangiocarcinoma in 5 patients (20%) (Table 2): 3 patients with type V cyst or Caroli's disease and 2 patients with type I cyst. The mean age of patients with cancer was 69 years with a range of 40–74 years.

Table 2.

Patients with Cancer Association

	Gender	Age	TB levels Umol/L	Carbohydrate antigen 19-9 (CA 19-9)	Cyst dimension cm	Todani type	Symptoms	Surgery	Postoperativecomplications	Recurrence	OS (months)	Mortality at last follow-up
01	F	40	75	990	8	I	Yes (abdominal pain)	Biliary tree resection	No	Yes	120	No
02	F	69	2	38,829	nn	V	No	Hepatic lobectomy	No	No	19.5	Yes
03	F	74	5	NEG	nn	V	No	Hepatic lobectomy	No	No	127.4	No
04	F	66	8.55	573	4	V	Yes (weight loss and abdominal pain)	Left hepatectomy	No	No	12.6	Yes
05	M	73	176	11,993	4.3	I	Yes (unpainful jaundice)	PD	No	No	5.8	No

NEG, nnegative; OS, overall survival; TB, total bilirubin.

Of these patients, only 2 patients presented with jaundice, both with Todani type I (Table 2).

Two patients died for cancer progression, both patients with Caroli's disease.

After a median follow-up of 59 months, 19 patients are alive, 4 patients died for other reasons, and 2 patients died for cancer evolution from BTCs.

Kaplan–Meyer curves for overall survival are shown in Figure 1.

FIG. 1.

OS curve (months). OS, overall survival.

Discussion

BTCs are a congenital rare disease that can be diagnosed incidentally, although BTCs should be thought of patients with an anamnesis characterized by several episodes of acute inflammation or several infections of gallbladder or biliary tree.

Wang et al.⁹ analyzed a series of 30 patients with Caroli's disease and only 13% of patients were completely asymptomatic, and diagnosis was made during examination conducted for other reasons, and likewise Wiseman et al.¹⁰ analyzed a series of 51 patients with choledochal cysts: 88% of them presented abdominal pain as first symptom and 37% of patients had recurrent episodes of cholangitis in anamnesis. Authors divided population by geographic origin in Caucasian and Asian patients and compared between the two groups of symptoms but there were no significant differences in presentation of BTCs.

Abdominal pain was the predominant symptom in our series (32%) and it was mostly correlated with Todani type V. Jaundice rates were 24% in preoperatory symptoms of our population. Edil et al.¹¹ analyzed a population of 92 patients comparing children and adults with choledochal cyst, jaundice was seen in 34% of overall population and it was statistically more frequent in the pediatric group. On the contrary, right upper quadrant pain was recorded as the more frequent symptom in the adult population than in the children group and this result was statistically significant.

Preoperatory jaundice was 21.6% in a Korean series¹² that enrolled 204 adult patients and this result is comparable with ours. Jaundice was associated with type III cyst (100%), type I (74%) and type V (25%) from our series, this result can be explained by anatomical predisposition in morphological anomalies involving CBD.

Malignancy is a well-known complication of BTCs. In our series, 5 patients (20%) were diagnosed of cholangiocarcinoma after pathological evaluation. Wiseman et al.¹⁰ evaluated jaundice association with patients with cancer development and patients without malignancy, and this correlation resulted statistically significant in the malignant correlated group (P < .05). Association between malignancy and jaundice was not statistically significant in our series.

A recent meta-analysis demonstrated that incidence of cancer on BTCs is still high (11%) and it is more associated with Todani type I and type IV.⁶ In our series, cancer was associated with Todani type I (2 patients) and Caroli disease (3 patients), 40% of them died for metastatic progression despite undergoing radical surgery. Furthermore, it seems to be a direct relationship between age and malignant transformation.¹³ In our series, mean age of patients with cancer was 69 years with a range of 40–74 years and there was no significant association between malignant degeneration and older patients.

Surgical treatment with complete excision of cyst based on Todani type plays a protective role to cancer transformation as seen in several series with a large number of patients enrolled.^14–16 Moreover, it is demonstrated that cystic drainage increases risk of malignant development compared with surgical excision.⁶ Lipsett et al.¹⁷ showed that surgery in young patients with BTCs was associated with a minimization of malignant evolution. From our series, the impact of surgery was acceptable: 90 days mortality was 0% and postoperative complications with Clavien–Dindo grade III–IV were recorded only in 2 patients (8%).

A Korean multicenter survey¹⁸ enrolled 808 patients surgically treated for BTCs. Ninety days mortality rate was low (0.2%) and postoperative morbidity was 12.9%; these results indicated how surgery still remains the best therapeutic option with few postoperative outcomes. Association with biliary malignant tumor was 9.9% and it was higher in older patients. Five years overall survival of patients with gallbladder or bile duct cancer was, respectively, 61.2% and 39.9%.

From our results, 5-year overall survival is 76% and 5-year overall survival in cancer group with BTCs was 60%; it is clear that surgical treatment for BTCs is a safe approach with low postoperative complication rates and minimizes the development of malignancy, which is higher in this group of disease and worst the prognosis.

Conclusions

BTCs are a heterogeneous group of anatomic alterations in biliary ducts that are associated with developing severe inflammatory processes such as cholangitis and pancreatitis. Moreover, there is a clear association with biliary malignancy. Despite the low incidence and the lack of specificity in symptoms, we have to consider them in patients with repeated biliary infections. Surgical treatment represents the treatment of choice and the only curative approach to these disorders and can be accomplished with a low mortality and morbidity rates.

Footnotes

Disclosure Statement

No competing financial interests exist.

Funding Information

The authors received no financial support for the research, authorship, and/or publication of this article.

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