Early-stage T1b adenocarcinoma arising in the remnant cystic duct after laparoscopic cholecystectomy: a case report and literature review
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The cystic duct has been included in the staging classification scheme for gallbladder cancer since the 2010 publication of the AJCC Cancer Staging Manual (7th edition). To our knowledge, only seven other cases of adenocarcinoma arising in the remnant cystic duct following cholecystectomy have been reported in the English-language literature, and none has been reported as primary early-stage T1b remnant cystic duct cancer (CDC). We report, herein, a case of primary adenocarcinoma arising in the remnant cystic duct in a patient with history of laparoscopic cholecystectomy for gallstone disease.
An 81-year-old female presented with abdominal pain. Her medical history included a laparoscopic cholecystectomy for cholecystolithiasis two years prior. Jaundice was observed; imaging studies suggested that this was caused by choledocholithiasis. Blood chemistry findings showed severe liver dysfunction. Endoscopic retrograde cholangiography revealed haemobilia from the common bile duct with no evidence of choledocholithiasis. A bile sample showed Papanicolaou class IV cytology. As the extent of tumour spread was undetermined by abdominal ultrasonography and endoscopic ultrasonography, peroral cholangioscopy (POCS) was performed, which revealed tiny papillary lesions within the confluence of cystic duct, and fine granular lesions in the centre of bile ducts, signifying early-stage remnant CDC. Extrahepatic bile duct resection with regional lymphadenectomy was done. Histopathological findings revealed a 42-mm tubular adenocarcinoma originating from the remnant cystic duct with the considerable shallow spread across the extrahepatic bile ducts. It invaded the fibromuscular layer, with no lymphovascular or perineural invasion, no lymph node metastasis (13 nodes examined), and uninvolved surgical resection margin (R0 resection), and was staged as pT1bN0M0, Stage I.
Primary early-stage T1b remnant CDC is an uncommon condition for which early diagnosis is challenging; if intraoperatively recognized, it can complicate surgery. Our experience of this case and an overview of the English literature suggest that POCS is an efficient tool to diagnosis this tumour and assess its spread along the extrahepatic bile ducts.
KeywordsGallbladder neoplasms Remnant cystic duct cancer Adenocarcinoma Early-stage Haemobilia Peroral cholangioscopy Surgery
American Joint Committee on Cancer
Cystic duct cancer
Endoscopic retrograde cholangiopancreatography
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 . 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.
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 ; 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 . Sakurai et al.  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 . 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 . The perimuscular connective tissue has more substantial lymphatic vessels than do the shallower layers . 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 . 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 . We previously reported that POCS is an efficient diagnostic option for early detection of biliary tract cancer . 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.
Cause of prior cholecystectomy
Histopathology and extent of tumor spread
Kuwayti et al. 
Phillips et al. 
Amputation of tumor mass, T-tube drainage
Dixon et al. 
Open biopsy, T-tube drainage
Involvement of the PV and RHA
Gabata et al. 
Involvement of the pancreatic duct
Noji et al. 
ERH, BD, Co
pT3N2M0 Involvement of the transverse colon
Eum et al. 
Involvement of the duodenum, pN0
Do et al. 
Acute cholecystitis with gallstone
WR, BD after removal of the remnant cystic duct
Chronic cholecystitis with gallstone
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.
We appreciate the contributions of all the surgeons, co-workers, and friends involved in this study and thank the editors and reviewers for their help with this manuscript.
Conception and design by TW, JS and YH; data collected by KM, KY, YH, KT, and TW; establishment of study materials or enrolment of patients by KM, KY, KT, KM, MN, TK, KN, AN; data scrutiny, analysis and clarification by KM, JS, PP, AN, YH and TW; manuscript writing by KM, PP, JS, YH and TW. All authors read and agreed with the final manuscript.
There are no resources of funding to be reported or declared.
Ethics approval and consent to participate
This study was approved by the Institutional Review Board of the Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan (2018–0137).
Consent for publication
Written informed consent was obtained from the patient‘s next of kin for publication of this case report and any accompanying images. A copy of the written consent is available for review by the Editor-in-Chief of this journal.
The authors declare that they have no competing interests.
- 1.Edge SB, Byrd DR, Compton CC, Fritz AG, Greene FL, Trotti A. American joint committee on Cancer staging manual. 7th ed. New York: Springer; 2010. p. 211–7.Google Scholar
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