Background

The cystic duct has been included in the staging classification scheme for gallbladder cancer since the 2010 publication of the American Joint Committee on Cancer (AJCC) Cancer Staging Manual,7th edition [1]. Early diagnosis of cystic duct cancer (CDC) is difficult, and when discovered intraoperatively, this tumour can add to the surgeon’s challenge. The development of adenocarcinoma in the remnant cystic duct following cholecystectomy is uncommon, with only seven cases reported in the English-language literature (PubMed, National Library of Medicine, Bethesda, MD, USA), Google Scholar, Web of Science and Scopus up to March 2019 [2,3,4,5,6,7,8]. Here, we report an instance of primary adenocarcinoma developing within a remnant cystic duct and evaluate the eight documented cases (including the present case) to characterize the clinicopathological attributes of this rare tumour.

Case presentation

An 81-year-old female presented with acute abdominal pain. Her medical history included laparoscopic cholecystectomy for cholecystolithiasis two years prior. The histopathological report of the resected gallbladder specimen revealed chronic cholecystitis with no evidence of malignancy. The patient was jaundiced, and imaging studies suggested that it was caused by choledocholithiasis. Abdominal ultrasonography (US) revealed no dilatation of the intrahepatic bile ducts. Blood chemistry findings revealed significantly elevated transaminases and biliary enzymes, which indicated severe liver dysfunction (glutamic oxaloacetic transaminase: 2328 IU/L; glutamic pyruvic transaminase: 2454 IU/L; alkaline phosphatase: 475 IU/L; lactate dehydrogenase: 3348 IU/L; total bilirubin: 3.5 mg/dL). Serum tumour markers were all within normal limits (carcinoembryonic antigen: 1.7 ng/mL; carbohydrate antigen 19–9: 19 U/mL). Endoscopic retrograde cholangiopancreatography (ERCP) revealed haemobilia from the orifice of ampulla of Vater (Fig. 1) with no evidence of choledocholithiasis, suggesting that the jaundice was caused by haemobilia. She was discharged from hospital.

Fig. 1
figure 1

Endoscopic retrograde cholangiopancreatography shows haemobilia from the orifice of ampulla of Vater. (From Nakamura A, Yagi K, Sekine A, Nihei K, Oyamatsu M, Tamiya Y. An early cystic duct carcinoma with hemobilia: Report of a Case. Journal of Gastroenterological Imaging [in Japanese] 2002;4(5):593–7; with permission)

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At the outpatient department, 4 months after discharge, abdominal US found a 1-cm mass lesion at the union of cystic and common hepatic ducts. ERCP revealed a filling defect at the cystic duct (Fig. 2). Endoscopic US (EUS) discovered a lesion in the remnant cystic duct (Fig. 3). Bile samples taken during ERCP revealed Papanicolaou class IV cytology. The extent of tumour spread was undetermined by abdominal US and EUS, but peroral cholangioscopy (POCS) revealed tiny papillary lesions within the confluence of the cystic duct (Fig. 4) and fine granular lesions in the middle bile duct, which signified early-stage remnant CDC. She underwent an extrahepatic bile duct resection with regional lymphadenectomy; no residual tumour was found. A retrocolic Roux-en-Y loop of the jejunum was brought up and was anastomosed to the exposed right and left hepatic ducts separately (hepaticojejunostomy). Macroscopically, the cause of haemobilia was bleeding from the remnant cystic duct tumour (Fig. 5a). Histological inspection showed a well-differentiated tubular adenocarcinoma originating from the remnant cystic duct with the considerable shallow spread across the extrahepatic bile ducts (Fig. 5b), 42 × 40 mm in size, that had invaded the fibromuscular layer (Fig. 6), but showed no lymphovascular or perineural invasion, no lymph node metastasis (13 examined lymph nodes), and uninvolved surgical resection margin (R0 resection), and was classified as pT1bN0M0, Stage I, based on the AJCC Cancer Staging Manual, 8th edition [9]. The patient had an uneventful recovery and was discharged. She died of another cause (colon cancer) with no evidence of recurrent CDC, 4 years after the surgery for remnant CDC.

Fig. 2
figure 2

Endoscopic retrograde cholangiography depicts filling defect at the cystic duct. (From Nakamura A, Yagi K, Sekine A, Nihei K, Oyamatsu M, Tamiya Y. An early cystic duct carcinoma with hemobilia: Report of a Case. Journal of Gastroenterological Imaging [in Japanese] 2002;4(5):593–7; with permission)

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Fig. 3
figure 3

Endoscopic ultrasonography shows mass lesion in the remnant cystic duct. (From Nakamura A, Yagi K, Sekine A, Nihei K, Oyamatsu M, Tamiya Y. An early cystic duct carcinoma with hemobilia: Report of a Case. Journal of Gastroenterological Imaging [in Japanese] 2002;4(5):593–7; with permission)

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Fig. 4
figure 4

Peroral cholangioscopy depicts tiny papillary lesions (arrowheads) around the confluence of the cystic duct and bleeding point from tumour itself (*). (From Nakamura A, Yagi K, Sekine A, Nihei K, Oyamatsu M, Tamiya Y. An early cystic duct carcinoma with hemobilia: Report of a Case. Journal of Gastroenterological Imaging [in Japanese] 2002;4(5):593–7; with permission)

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Fig. 5
figure 5

Resected specimen. a bleeding point (arrowhead) from the remnant cystic duct tumour. b red lines: area of T1 tumour; blue lines: area of tumour invasion of fibromuscular layer. (From Nakamura A, Yagi K, Sekine A, Nihei K, Oyamatsu M, Tamiya Y. An early cystic duct carcinoma with hemobilia: Report of a Case. Journal of Gastroenterological Imaging [in Japanese] 2002;4(5):593–7; with permission)

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Fig. 6
figure 6

Adenocarcinoma invading fibromuscular layer (arrowheads)

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Discussion and conclusions

Here, we present an uncommon entity, primary early-stage T1b adenocarcinoma arising in the remnant cystic duct following laparoscopic cholecystectomy. We reviewed the English-language literary works (PubMed, National Library of Medicine, Bethesda, MD, USA) published from January 1966 through March 2019, using the following Medical Subject Heading (MeSH) terms: “cystic duct” or [“surgery” and “gallbladder neoplasms”] in combination with “remnant cystic duct cancer”, “bile duct neoplasms”, “treatment outcome”, and/or “follow-up study.” References from the included articles were searched to identify additional cases and revealed that a total of seven patients who had undergone cholecystectomy suffered from subsequent remnant CDC following cholecystectomy [2,3,4,5,6,7,8]. To our knowledge, this is a first case in the English-language literature of primary early-stage T1b adenocarcinoma arising in the remnant cystic duct with a patient having history of laparoscopic cholecystectomy for gallstone disease.

In 1951, Farrar suggested diagnostic standards for CDC, which included (1) progression limited to within the cystic duct, (2) no neoplastic process in the gallbladder or hepatic or common bile duct, and (3) histological confirmation of malignant cells [10]; which the present case fulfils. In our case, tumour invasion was up to fibromuscular layer and limited within the remnant cystic duct (Fig. 5), the prior resected gallbladder specimen showed chronic cholecystitis with no evidence of malignancy, and histopathological findings provided a diagnosis of primary early-stage T1b adenocarcinoma arising in the remnant cystic duct.

Symptoms may appear more readily in early-stage remnant CDC than in gallbladder cancer. The cystic duct obstruction may cause symptoms like abdominal pain and jaundice as the gallbladder becomes distended, ultimately resulting in cholecystitis with fever, chills and inflammation [8]. Sakurai et al. [11] documented a case of early CDC, in which invasion was restricted to the fibromuscular layer; the papillary tumour projected into the common bile duct, remote from the junction of the cystic duct, to reach the common bile duct, causing obstructive jaundice. However, in the present case of a remnant CDC, the latter symptoms were jaundice and concomitant haemobilia, which was difficult to diagnose by conventional radiological modalities. In contrast, bleeding pseudoaneurysm of the cystic artery due to chronic cholecystitis treated by endovascular embolization and subsequent cholecystectomy have been well designated [12]. We noticed that the originating site of haemobilia was itself a tumour (Figs. 4 and 5 a). This is quite a rare phenomenon, with little published literature pertaining to this clinical feature.

Primary early-stage CDC is challenging to confirm, even in the twenty-first century. It may possibly characterize as a peril factor if it occurs as an intrusive neoplasm in the identical site. The cystic duct is pretty small and joins the gallbladder to the common bile duct. Its surfaces essentially incorporate four layers: mucosa (epithelium, lamina propria), muscle layer, perimuscular connective tissue, and serosa [1]. The perimuscular connective tissue has more substantial lymphatic vessels than do the shallower layers [13]. Due to their distinctive structure and site, carcinomas caused by the cystic duct are referred to as gallbladder carcinomas and therefore are thought to simply interfere with surrounding organs and lymph nodes [14]. Because of this, early-stage CDCs are leading-edge if they are identified. Early-stage CDC is very uncommon; documented cases account for only 0.03–0.05% of all autopsies [14]. We previously reported that POCS is an efficient diagnostic option for early detection of biliary tract cancer [15]. In the present case, POCS was useful in determining the superficial ductal spread of the cancerous area to achieve negative margins. We experienced that POCS is an efficient tool regarding diagnosis and determination of extent of tumour spread along the extrahepatic bile ducts.

Table 1 summarizes reported cases of remnant CDC. The extent of tumour spread included distant liver metastasis [3], tumours directly invading other adjacent organs, such as the pancreas [5], colon [6], and duodenum [7], and tumour invading to the main portal vein and hepatic artery [4], which indicates that detection of this tumour at later stages may lead to dismal outcomes. Do et al. [8] reported a case of adenocarcinoma, histopathologically diagnosed as pT2N0M0, that developed from the remnant cystic duct after cholecystectomy; its spread limited to the gallbladder viscus and the patient was alive 1 year after surgery with no recurrence.

Table 1 Summary of the reported cases of remnant cystic duct cancer [2,3,4,5,6,7,8]
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Appropriate surgical treatment for remnant CDC is en bloc resection of the cystic duct, common bile duct, and regional lymphadenectomy, which could be the pillar of the treatment method. Among the eight reported cases (including the present case) in Table 1, early-stage (pT1bN0M0) remnant CDC was successfully recognized in our case, and the patient survived 4 years after its en bloc resection, with no evidence of recurrence. Thus, early detection and radical resection may improve outcomes in patients with remnant CDC. Primary early-stage T1b remnant CDC is an uncommon condition that cannot be easily diagnosed in its early stages. If serendipitously recognized during surgery, this tumour may greatly increase the difficulty of a procedure. Our understanding with this case and literature review indicates that POCS is an efficient tool for diagnosing this tumour and determining the extent its spread along the extrahepatic bile ducts. Wider study from multicentre institutes is needed to validate the long-term survival outcomes.