[Cystic duct carcinoma in a patient with a history of cholecystectomy: a case report].

An 83-year-old Japanese man who underwent cholecystectomy for cholecystolithiasis 17 years ago visited our hospital owing to epigastric pain. He was initially diagnosed with choledocholithiasis and acute cholangitis following white blood cell, C-reactive protein, total bilirubin, alkaline phosphatase, and γ-glutamyltranspeptidase level elevations along with common bile duct stones on computed tomography (CT). Moreover, CT, magnetic resonance imaging, endoscopic retrograde cholangiography (ERC), and endoscopic ultrasonography (EUS) also revealed a 2-cm-diameter mass arising from the remnant cystic duct. The cytology of the bile at the time of ERC was not conclusive. However, EUS-assisted fine needle aspiration (EUS-FNA) of the mass confirmed the diagnosis of adenocarcinoma of the remnant cystic duct. The patient underwent extrahepatic bile duct resection. Cystic duct carcinoma following cholecystectomy is rare. We report a case diagnosed by EUS-FNA.

Clinical implication of the geometric location (fundal end versus cystic ductal end) of gallbladder cancer.

BACKGROUND: Management of early-stage gallbladder cancer is becoming more important as the rate of early detection is increasing. Although there have been many studies about the clinical implication of the invasion depth or peritoneal/hepatic location of gallbladder cancers, there is no study on the clinical implication of the geometric location of cancer along the longitudinal length of the gallbladder. METHODS: The location of gallbladder cancer was defined as the geometric center of the primary site of a tumour, which lies on the longitudinal diameter of the surgical specimens. We compared the oncologic outcomes following surgery between gallbladder cancers located on the fundal end and those located on the cystic ductal end. We also analysed patients with stage 1 gallbladder cancer who recurred after surgery. RESULTS: A total of 575 patients with gallbladder cancer were included in this study. Patients with gallbladder cancer on the cystic ductal end had significantly lower rates of recurrence-free survival (P = 0.016) and overall survival (P = 0.023) compared to those with gallbladder cancer on the fundal end. Among 90 patients with stage 1 gallbladder cancer, three patients had a recurrence, all of whom had cystic ductal end gallbladder cancer and showed cystic duct invasion or concomitant xanthogranulomatous cholecystitis in permanent pathology. CONCLUSIONS: Gallbladder cancers on the cystic ductal end had worse postoperative oncologic outcomes compared with those on the fundal end.

High-grade dysplasia of the cystic duct margin: how should this be managed?

High-grade dysplasia (HGD) in the cystic duct is a rare epithelial lesion that may lead to biliary tract malignancy. Due to its association with aggressive multifocal cholangiocarcinoma, it is important to investigate for concurrent malignancy, remove all areas of HGD and monitor for recurrence or metastasis.We present a case of a woman in her 60s with cholecystitis who underwent a laparoscopic cholecystectomy. On histopathology, the patient was found to have incidental HGD involving the cystic duct margin. After ensuring the absence of concurrent malignancy on cross-sectional imaging, she underwent further resection until the margins were clear of dysplasia. In the absence of clear follow-up guidelines, the patient was closely monitored with outpatient scans for up to 5 years.

The Significance of Tumor Locations in Patients with Gallbladder Carcinoma After Curative-Intent Resection.

OBJECTIVE: To evaluate the significance of tumor locations in patients with resected gallbladder carcinoma (GBC) and to supply the indication of extra-hepatic bile duct resection (EHBDR) according to tumor locations. METHODS: Patients with resected GBC from 2010 to 2020 in our hospital were retrospectively analyzed. Comparative analyses and a meta-analysis were performed according to different tumor locations (body/fundus/neck/cystic duct). RESULTS: Article: A total of 259 patients were identified (neck: 71; cystic: 29; body: 51; fundus: 108). Patients with proximal tumors (neck/cystic duct) were often in a more advanced stage and had more aggressive tumor biological features as well as a worse prognosis compared with those with distal tumors (fundus/body). Moreover, the observation was even more obvious between cystic duct and non-cystic duct tumors. Cystic duct tumor was an independent prognostic factor for overall survival (P = 0.01). EHBDR provided no survival advantage even in those with cystic duct tumor. META-ANALYSIS: With our own cohort incorporated, five studies with 204 patients with proximal tumors and 5167 patients with distal tumors were identified. Pooled results revealed that proximal tumors indicated worse tumor biological features and prognosis versus distal tumors. CONCLUSION: Proximal GBC had more aggressive tumor biological features, and a worse prognosis versus distal GBC and cystic duct tumor can be regarded as an independent prognostic factor. EHBDR had no obvious survival advantage even in those with cystic duct tumor and was even harmful in those with distal tumors. Upcoming more powerful well-designed studies are required for further validation.

Diagnostic usefulness of SpyGlass in intracholecystic papillary neoplasm with pancreaticobiliary maljunction: a case report and comparison with conventional gallbladder cancer with pancreaticobiliary maljunction.

BACKGROUND: Intracholecystic papillary neoplasm (ICPN) is one of the precursors of gallbladder cancer defined in the 2010 World Health Organization classification of tumors. We herein report ICPN with pancreaticobiliary maljunction (PBM), which is a high-risk factor for biliary cancer. CASE PRESENTATION: A 57-year-old female presented with abdominal pain. Computed tomography showed a swollen appendix and gallbladder nodules with bile duct dilatation. Endoscopic ultrasonography revealed a gallbladder tumor spreading into the cystic duct confluence accompanying PBM. Based on papillary tumors around the cystic duct detected using the SpyGlass DS II Direct Visualization System (SpyGlass DS), ICPN was suspected. We performed extended cholecystectomy, extrahepatic bile duct resection, and appendectomy with a diagnosis of ICPN and PBM. The pathological diagnosis was ICPN (90 × 50 mm) with high-grade dysplasia spreading into the common bile duct. The absence of residual cancer in the resected specimen was pathologically confirmed. P53 staining was totally negative in both the tumor and normal epithelium. The overexpression of CTNNB1 was not observed. CONCLUSIONS: We encountered a patient with a very rare gallbladder tumor, ICPN with PBM. SpyGlass DS contributed to a precise assessment of the extent of the tumor as well as a qualitative diagnosis.

Polypoid-Type Adenomyomatous Lesion of the Cystic Duct: Report of a Case and Review of Literature.

Adenomyomatous hyperplasia, a common non-neoplastic lesion in the gallbladder, is rarely identified in the extrahepatic bile duct. Typically, these lesions appear as a nodule or mural thickening/elevation. However, in exceptional circumstances, pedunculated/polypoid adenomyomatous lesion occurs in the biliary tract; two cases in the gallbladder and only one case in the common bile duct have been reported. Despite their benign nature, adenomyomatous lesions, especially those with a polypoid appearance, are clinically difficult to exclude a possibility of malignant neoplasms. We describe a case of polypoid-type adenomyomatous lesion of the cystic duct in a 72-year-old man, which was considered as a cystic duct neoplasm preoperatively. Gross examination of the resected specimen revealed that the 9 mm-sized cystic duct polyp. Histologically, the polypoid lesion consisted of glands without atypia, fibrous stroma, smooth muscle bundles, and accompanying stromal inflammation, leading to the diagnosis of benign adenomyomatous lesion. The lesion might be considered as adenomyomatous hyperplasia arising in the valve of Heister, while true nature of the lesion is uncertain. Recognition and accumulating for this rare disease will contribute to better clinical management in the future.

Perivascular epithelioid cell tumor (PEComa) of the cystic duct.

Perivascular epithelioid cell tumors, also known as PEComas, are rare mesenchymal tumors composed mainly of epithelioid cells found in perivascular tissue. PEComas occur most frequently in the kidney, uterus, the gastrointestinal tract, liver, and retroperitoneum; those originating in the biliary tree are extremely rare. We report a case of benign PEComa of the cystic duct with positive TFE3 staining on immunohistochemistry.A 66-year-old woman was referred for a 20 mm mass adjacent to the common bile duct discovered incidentally on abdominal ultrasound. Laboratory data including tumor markers were unremarkable. The tumor appeared to arise from the cystic duct, showed early enhancement, and compressed the common bile duct on imaging studies. Endoscopic ultrasound-guided fine-needle aspiration revealed round- and spindle-shaped atypical cells with eosinophilic cytoplasm and brown deposits suggestive of melanin granules. Histological examination of the resected specimen revealed a tumor consisting of epithelioid cells forming an alveolar structure, with melanin pigmentation. Immunohistochemistry was positive for HMB-45 and TFE3, consistent with benign pigmented PEComa of the cystic duct. Melanotic, myogenic, and TFE3 staining are helpful when diagnosing PEComas arising in unusual locations.

A Preoperative Diagnosis of Advanced Cystic Duct Carcinoma Using SpyGlass DS Cholangioscopy: A Report of Two Cases.

Primary cystic duct carcinoma is a rare tumor. The curative treatment of cystic duct carcinoma is complete surgical resection, for which the evaluation of local extension is important. We herein report two cases of cystic duct carcinoma in which a preoperative examination was performed using per-oral cholangioscopy (POCS). Both patients underwent POCS due to suspicion of cystic duct carcinoma based on imaging findings. A visual analysis and biopsy were performed to evaluate local extension, which led to surgery. These cases suggest that POCS is useful for the preoperative assessment of local extension in advanced cystic duct carcinoma.

[Squamous cell carcinoma of the gallbladder complicating a cystic dilation of the cystic duct and common bile duct: a case report]. / Carcinome épidermoïde de la vésicule biliaire compliquant une dilatation kystique de la voie biliaire principale (VBP) et du canal cystique: à propos d´un cas.

Congenital cystic disease of the biliary tree is a known risk factor for gallbladder cancer. We here report a case of squamous cell carcinoma of the bile duct (BD) complicating a cystic dilatation of the bile ducts in a 54-year-old woman hospitalized for biliary pancreatitis. Abdominal scanner showed nodular thickening of the fundus of the gallbladder and fusiform dilation of the cystic duct and the main bile duct (VBP) with lesion of the tail of the pancreas, initially suggesting mucinous cystadenoma. Extended cholecystectomy involving the gallbladder fossa with resection of the distal biliary tract, choledocoduodenal anastomosis with caudal splenopancreatectomy + drainage were performed. Histopathological examination of the gallbladder mass revealed moderately differentiated invasive squamous cell carcinoma without infiltration of the hepatic parenchyma. The patient underwent adjuvant chemotherapy. The patient did not have the common symptoms of gallbladder cancer. Then radiology was necessary to make a diagnosis. Surgery is the best therapeutic option for early-stage gallbladder cancer, but adjuvant chemo-radiation may also be useful in treating these patients. Cholecystectomy with resection of cystic dilatation of the bile duct in high-risk patients are the most effective means of prevention.

Applicability of sentinel lymph node oriented treatment strategy for gallbladder cancer.

BACKGROUND: Utility of the sentinel lymph node (SLN) biopsy in some malignancies has been reported, however, research on that of gallbladder cancer (GBC) is rare. The aim of this study is to investigate whether the concept of SLN is applicable to T2/3 GBC. METHODS: A total of 80 patients who underwent resection for gallbladder cancer were enrolled in this study. Patients with GBC were stratified into two groups based on the location of tumor, peritoneal-side (T2p or 3p) and hepatic-side (T2h or 3h) groups. We evaluated the relationship between cystic duct node (CDN) and downstream lymph node (LN) status. CDN was defined as a SLN in this study. RESULTS: Thirty-eight patients were classified into T2, including T2p (n = 18) and T2h (n = 20), and 42 patients into T3, including T3p (n = 22) andT3h (n = 20). The incidence of LN metastasis was significantly higher in hepatic-side than peritoneal-side in both T2 and T3 (P = 0.036 and 0.009, respectively). In T2, 14 T2p had negative CDN and downstream LN, however, three T2h had negative CDN and positive downstream LNs (defined as a skipped LN metastasis) (P = 0.043). In T3, patients with skipped LN metastasis were significantly higher in T3h (n = 11) than those in T3p (n = 2) (P<0.001). There was no recurrence of the local lymph node. Disease-free survival in the T2p and T3p were significantly better than those in the T2h and T3h (P = 0.005 and 0.025, respectively). CONCLUSION: The concept of SLN can be applicable to T2p GBC, where the downstream LNs dissection can be omitted.

Dilation of the cystic duct confluence in laparoscopic common bile duct exploration and stone extraction in patients with secondary choledocholithiasis.

BACKGROUND: Many options exist for the management of cholelithiasis and secondary choledocholithiasis. Among them, laparoscopic common bile duct exploration (LCBDE) with choledocotomy followed by laparoscopic cholecystectomy has gained popularity. However, efforts should be made to ensure minimally invasive or noninvasive management of the common bile duct (CBD). The purpose of this study was to explore the clinical experience of non-invasive surgical modality, i.e., laparoscopic transcystic dilation of the cystic duct confluence in CBD exploration (LTD-CBDE), including feasibility, safety, adverse events, and incidence. METHODS: In this retrospective analysis, 68 patients were offered the LTD-CBDE technique from December 2015 to April 2018 based on patient's own intention. During the surgery, the cystic duct confluence was dilated with separation forceps and/or a columnar dilation balloon. Subsequently, CBD exploration and stone extraction were performed with a choledochoscope. The entrance of the CBD was covered with a cystic duct stump wall and was subjected to primary closure at the end of surgery. RESULTS: Forty-nine females and 19 males with cholelithiasis and secondary choledocholithiasis were included. The mean age was 53 years old (18 to 72 year). Of these patients, 62 (91.2%) were successfully treated with the LTD-CBDE technique, and bile leakage was observed in 3 patients (4.4%). The mean operation time was 106 min, and the mean hospital stay was 5.9 days. Among the other 6 patients, 3 were converted to open cholecystectomy due to severe fibrosis, unclear anatomical structure at Calot's triangle (n = 2) or Mirizze syndrome (n = 1); LCBDE was performed in 3 patients due to cystic duct atresia (n = 2) and low level of flow from the gallbladder duct into the CBD (n = 1). These patients had a smooth postoperative course. In total, 43/68 of the patients presented no radiological evidence of retained CBD stones at the postoperative follow-up (40 patients treated with LTD-CBDE) 1 year later. CONCLUSIONS: The current work suggests that LTD-CBDE for the management of cholelithiasis and secondary choledocholithiasis is a feasible, safe and effective technique with a low complication rate. LTD-CBDE offers another alternative for surgeons to treat patients in similar scenarios. However, additional randomized, controlled studies are needed to demonstrate its efficacy, safety, and impact on CBD stenosis.

Clinicopathologic and Prognostic Significance of Gallbladder and Cystic Duct Invasion in Distal Bile Duct Carcinoma.

CONTEXT.­: The roles of the gallbladder and cystic duct (CD) invasions in distal bile duct carcinoma (DBDC) have not been well elucidated. OBJECTIVE.­: To define the characteristics and prognostic significance of gallbladder or CD invasions in patients with DBDC. DESIGN.­: Organ invasion patterns with clinicopathologic features were assessed in 258 resected DBDCs. RESULTS.­: CD invasions (N = 31) were associated with frequent concomitant pancreatic and/or duodenal invasions (23 of 31, 74%) and showed stromal infiltration (16 of 31, 52%) and intraductal cancerization (15 of 31, 48%) patterns. In only 2 cases, invasions with intraductal cancerization were observed in the gallbladder neck. Conversely, all pancreatic (N = 175) and duodenal (83) invasions developed through stromal infiltration. CD invasions were associated with larger tumor size (P = .001), bile duct margin positivity (P = .001), perineural invasions (P = .04), and higher N categories (P = .007). Patients with pancreatic or duodenal invasions had significantly lower survival rates than those without pancreatic (median, 31.0 versus 93.9 months) or duodenal (27.5 versus 56.8 months, P < .001, both) invasions. However, those with gallbladder or CD invasions did not have different survival times (P = .13). Patients with concomitant gallbladder/CD and pancreatic/duodenal invasions demonstrated significantly lower survival rates than those without organ invasions (P < .001). CONCLUSIONS.­: Gallbladder invasions were rare in DBDCs as neck invasions with intraductal cancerization. CD invasions occurred by stromal infiltrations and intraductal cancerization, whereas all pancreatic and duodenal invasions had stromal infiltration patterns. Gallbladder and/or CD invasions did not affect survival rates of patients with DBDC, while pancreatic and duodenal invasions affected survival rates. Therefore, these differences in survival rates may originate from the different invasive patterns of DBDCs.

Cystic duct cancer: Should it be deemed as a type of gallbladder cancer?

BACKGROUND: According to the latest American Joint Committee on Cancer and Union for International Cancer Control manuals, cystic duct cancer (CC) is categorized as a type of gallbladder cancer (GC), which has the worst prognosis among all types of biliary cancers. We hypothesized that this categorization could be verified by using taxonomic methods. AIM: To investigate the categorization of CC based on population-level data. METHODS: Cases of biliary cancers were identified from the Surveillance, Epidemiology, and End Results 18 registries database. Together with routinely used statistical methods, three taxonomic methods, including Fisher's discriminant, binary logistics and artificial neuron network (ANN) models, were used to clarify the categorizing problem of CC. RESULTS: The T staging system of perihilar cholangiocarcinoma [a type of extrahepatic cholangiocarcinoma (EC)] better discriminated CC prognosis than that of GC. After adjusting other covariates, the hazard ratio of CC tended to be closer to that of EC, although not reaching statistical significance. To differentiate EC from GC, three taxonomic models were built and all showed good accuracies. The ANN model had an area under the receiver operating characteristic curve of 0.902. Using the three models, the majority (75.0%-77.8%) of CC cases were categorized as EC. CONCLUSION: Our study suggested that CC should be categorized as a type of EC, not GC. Aggressive surgical attitude might be considered in CC cases, to see whether long-term prognosis could be immensely improved like the situation in EC.

Early-stage T1b adenocarcinoma arising in the remnant cystic duct after laparoscopic cholecystectomy: a case report and literature review.

BACKGROUND: 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. CASE PRESENTATION: 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. CONCLUSIONS: 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.

Incidental high-grade dysplasia of the cystic duct margin: case report and literature review.

High-grade dysplasia (HGD) of the gallbladder has been proven to be an intermediate step in the pathogenesis from normal mucosa to invasive carcinoma. There is paucity of definitive data concerning the associated risk and optimal management of isolated HGD of the gallbladder involving the cystic duct margin following cholecystectomy. A previously healthy 44-year-old man underwent laparoscopic cholecystectomy for suspected symptomatic gallstones. The gross examination of the gallbladder did not show any discrete masses or lesions, and histopathologic evaluation revealed several proximal foci of HGD with involvement of the cystic duct margin. Subsequent magnetic resonance cholangiopancreatography (MRCP) showed central intra-hepatic ductal dilation, likely post-operative, with no evidence of malignancy. Patient underwent additional surgical exploration with laparoscopic excision of the cystic duct stump and intra-operative cholangiogram. The additionally resected stump showed mild chronic inflammation and reparative fibrosis without dysplasia. A follow-up MRCP two years later showed regression of the previously described dilation and no new lesions were detected. The patient remains disease-free until the present date. Isolated HGD of the gallbladder is an uncommon occurrence but can rarely involve the cystic duct margin. These patients are to be thoroughly investigated for associated carcinoma in other parts of the gallbladder. Additional studies are needed to better understand the long-term risk associated with premalignant lesions of the gallbladder to achieve optimal care and outcome for these patients.

Intracholecystic papillary-tubular neoplasm of the gallbladder originating in the cystic duct with extensive intraepithelial progress in the common bile duct.

A 59-year-old man with anorexia who had a history of cholecystectomy was referred to our hospital. Imaging examinations revealed a contrast-enhanced tumor in the residual cystic duct and a part of the common bile duct. Endoscopic retrograde cholangiopancreatography and peroral-cholangioscopy showed a papillary tumor with movement and a change in the shape. Under a diagnosis of primary cystic duct cancer, subtotal stomach-preserving pancreaticoduodenectomy was performed. The microscopic examination of a resected specimen revealed intracholecystic papillary-tubular neoplasm located in the residual cystic duct, forming a polypoid protrusion to the common bile duct and extensive intraepithelial progress in the common bile duct.

Type VI choledochal cyst with gall bladder carcinoma.

An isolated dilatation of the cystic duct (type VI choledochal cyst (CDC)) is extremely rare with only 21 cases reported in the world literature until now. There is only one case of in situ gall bladder cancer (GBC) reported in association with type VI CDC in the literature. Here we are reporting a case of type VI CDC with papillary GBC.