Rare primary squamous cell carcinoma of the intrahepatic bile duct: A case report and review of literature

BACKGROUND Cholangiocarcinoma is the most common malignancy of the biliary tree and has a poor prognosis.Adenocarcinoma is the most common pathological type of cho-langiocarcinomas,but rare squamous,adenosquamous,and mucinous variants have been reported without adequate clinical data.CASE SUMMARY This report describes a rare case of primary squamous cell carcinoma(SCC)of the intrahepatic bile duct.The patient was admitted with a tumor in the hepatic caudate lobe with no obvious clinical symptoms.Examination revealed hepatitis B surface antigen positivity,a slight increase in alfa-fetoprotein to 16.34 ng/mL,and an irregular slightly heterogeneous enhancing lesion in the hepatic caudate lobe,which was initially thought to be hepatocellular carcinoma.Laparoscopic re-section was performed,and the final pathology suggested a rare primary SCC of the intrahepatic bile duct.Immunohistochemistry indicated positivity for villin,partial positivity for p63,and negativity for hepatocyte,CK7,CK8,CK19,and CK20.The Ki-67 index was approximately 60%.The patient received six cycles of Tegio chemotherapy.A new lesion was detected in the liver after 15 months.The surgery was performed,and the patient was followed-up at a local hospital.To date,no new lesions have been observed.CONCLUSION Surgery is the first choice for resectable lesions,and combined chemotherapy based on pathology is essential for increasing overall survival.

Removal of intrahepatic bile duct stone could reduce the risk of cholangiocarcinoma: A single-center retrospective study in South Korea

BACKGROUND Intrahepatic duct(IHD)stones are among the most important risk factors for cholangiocarcinoma(CCC).Approximately 10%of patients with IHD stones develop CCC;however,there are limited studies regarding the effect of IHD stone removal on CCC development.AIM To investigate the association between IHD stone removal and CCC development.METHODS We retrospectively analyzed 397 patients with IHD stones at a tertiary referral center between January 2011 and December 2020.RESULTS CCC occurred in 36 of the 397 enrolled patients.In univariate analysis,chronic hepatitis B infection(11.1%vs 3.0%,P=0.03),carbohydrate antigen 19-9(CA19-9,176.00 vs 11.96 II/mL,P=0.010),stone located in left or both lobes(86.1%vs 70.1%,P=0.042),focal atrophy(52.8%vs 26.9%,P=0.001),duct stricture(47.2%vs 24.9%,P=0.004),and removal status of IHD stone(33.3%vs 63.2%,P<0.001)were significantly different between IHD stone patients with and without CCC.In the multivariate analysis,CA19-9>upper normal limit,carcinoembryonic antigen>upper normal limit,stones located in the left or both lobes,focal atrophy,and complete removal of IHD stones without recurrence were independent factors influencing CCC development.However,the type of removal method was not associated with CCC risk.CONCLUSION Complete removal of IHD stones without recurrence could reduce CCC risk.

Diagnosis of bile duct hepatocellular carcinoma thrombus without obvious intrahepatic mass

AIM:To study the diagnosis of hepatocellular carcinoma(HCC)presenting as bile duct tumor thrombus with no detectable intrahepatic mass.METHODS:Six patients with pathologically proven bile duct HCC thrombi but no intrahepatic mass demonstrated on the preoperative imaging or palpated intrahepatic mass during operative exploration,were collected.Their clinical and imaging data were retrospectively analyzed.The major findings or signs on comprehensive imaging were correlated with the surgical and pathologic findings.RESULTS:Jaundice was the major clinical symptom of the patients.The elevated serum total bilirubin,direct bilirubin and alanine aminotransferase levels were in concordance with obstructive jaundice and the underlying liver disease.Of the 6 patients showing evidence of viral hepatitis,5 were positive for serum alpha fetoprotein and carbohydrate antigen 19-9,and 1 was positive for serum carcinoembryonic antigen.No patient was correctly diagnosed by ultrasound.The main features of patients on comprehensive imaging were filling defects with cup-shaped ends of the bile duct,with large filling defects presenting as casting moulds in the expanded bile duct,hypervascular intraluminal nodules,debris or blood clots in the bile duct.No obvious circular thickening of the bile duct walls was observed.CONCLUSION:Even with no detectable intrahepatic tumor,bile duct HCC thrombus should be considered in patients predisposed to HCC,and some imaging signs are indicative of its diagnosis.

Primary signet-ring cell carcinoma of the extrahepatic bile duct:A case report

BACKGROUND Signet ring cell carcinoma(SRCC)is a specific type of mucinous secretory adenocarcinoma,which contains abundant mucus in the cytoplasm and pushes the nucleus to one side of the cell membrane,forming a round or oval,and the nuclear deviations give the cells a signet ring-like appearance.SRCC often originates in the gastrointestinal tract,especially in the stomach.However,primary SRCC of the extrahepatic bile duct is extremely rare.Therefore,little is known about its epidemiology,treatment,and prognosis.CASE SUMMARY An 82-year-old female was admitted with abdominal pain,jaundice,and skin pruritus for 2 mo.She had no specific family history.Physical examination presented normal vital signs,icteric sclera,visible jaundice,and mild tenderness in the right upper abdominal quadrant.Tumor-related cell markers were within normal values.Contrast-enhanced computed tomography revealed a thickened wall of the common bile duct,strengthened with intrahepatic bile duct dilation and multiple round-like lesions in the liver.In addition,the lymph nodes in the hepatic hilum area,the pancreatic head area,and around the abdominal aorta were enlarged.Thus,a preoperative diagnosis of cholangiocarcinoma was established.To alleviate jaundice and prolong the overall survival,percutaneous transhepatic cholangiopancreatic drainage(PTCD)was performed.During the operation,segmental stenosis of the extrahepatic bile duct and a vine-like expansion of the intrahepatic bile duct was observed.Furthermore,a biliary biopsy was performed under fluoroscopy to determine the nature and origin of the lesion.The pathological diagnosis of the biopsy was SRCC.Finally,a diagnosis of primary SRCC of extrahepatic bile duct with distant lymph node metastasis and multiple liver metastases was made based on the radiographic,PTCD,and pathological characteristics.The tumor was diagnosed as T3N1M1 stage IV.Despite our aggressive approach,the patient died of liver failure after 1 mo.CONCLUSION This is the only case report on primary SRCC of the extrahepatic bile duct with distant organ metastasis to date.

Endoscopic diagnosis of extrahepatic bile duct carcinoma:Advances and current limitations

The accurate diagnosis of extrahepatic bile duct carcinoma is difficult,even now.When ultrasonography(US)shows dilatation of the bile duct,magnetic resonance cholangiopancreatography followed by endoscopic US(EUS)is the next step.When US or EUS shows localized bile duct wall thickening,endoscopic retrograde cholangiopancreatography should be conducted with intraductal US(IDUS)and forceps biopsy.Fluorescence in situ hybridization increases the sensitivity of brush cytology with similar specificity.In patients with papillary type bile duct carcinoma,three biopsies are sufficient.In patients with nodular or infiltrating-type bile duct carcinoma,multiple biopsies are warranted,and IDUS can compensate for the limitations of biopsies.In preoperative staging,the combination of dynamic multidetector low computed tomography(MDCT)and IDUS is useful for evaluating vascular invasion and cancer depth infiltration.However,assessment of lymph nodes metastases is difficult.In resectable cases,assessment of longitudinal cancer spread is important.The combination of IDUS and MDCT is useful for revealing submucosal cancer extension,which is common in hilar cholangiocarcinoma.To estimate the mucosal extenextension,which is common in extrahepatic bile duct carcinoma,the combination of IDUS and cholangioscopy is required.The utility of current peroral cholangioscopy is limited by the maneuverability of the“baby scope”.A new baby scope(10 Fr),called“SpyGlass”has potential,if the image quality can be improved.Since extrahepatic bile duct carcinoma is common in the Far East,many researchers in Japan and Korea contributed these studies,especially,in the evaluation of longitudinal cancer extension.

Intraductal papillary neoplasm of the bile duct in liver cirrhosis with hepatocellular carcinoma

A case of intraductal papillary neoplasm of the bile duct (IPNB) arising in a patient with hepatitis B-related liver cirrhosis with hepatocellular carcinoma (HCC) is reported. A 76-year-old man was admitted to our hospital with recurrent HCC. Laboratory data showed that levels of carcinoembryonic antigen and carbohydrate antigen 19-9 were elevated. He died of progressive hepatic failure. At autopsy,in addition to HCCs,an intraductal papillary proliferation of malignant cholangiocytes with fibrovascular cores was found in the dilated large bile ducts in the left lobe,and this papillary carcinoma was associated with an invasive mucinous carcinoma (invasive IPNB). Interestingly,extensive intraductal spread of the cholangiocarcinoma was found from the reactive bile ductular level to the interlobular bile ducts and septal bile ducts and to the large bile ducts in the left lobe. Neural cell adhesion molecule,a hepatic progenitor cell marker,was detected in IPNB cells. It seems possible in this case that hepatic progenitor cells located in reactive bile ductules in liver cirrhosis may have been responsible for the development of the cholangiocarcinoma and HCC,and that the former could have spread in the intrahepatic bile ducts and eventually formed grossly visible IPNB.

Neuroendocrine carcinoma of the common hepatic duct coexisting with distal cholangiocarcinoma:A case report and review of literature

BACKGROUND Neuroendocrine carcinoma(NEC)of the extrahepatic bile duct is very rare,and the treatment and prognosis are unclear.Herein,we report the case of a middleaged female with primary large cell NEC(LCNEC)of the common hepatic duct combined with distal cholangiocarcinoma(dCCA).Additionally,after a review of the relevant literature,we summarize and compare mixed neuroendocrine-nonneuroendocrine neoplasm(MiNEN)and pure NEC to provide a reference for selecting the appropriate treatment and predicting the prognosis of this rare disease.CASE SUMMARY A 62-year-old female presented to the hospital due to recurrent abdominal pain for 2 months.Physical examination showed mild tenderness in the upper abdomen and a positive Courvoisier sign.Blood tests showed elevated liver transaminase and carbohydrate antigen 199 levels.Imaging examination revealed node dissection was performed,and hepatic duct tumours were unexpectedly found during surgery.Pathology suggested poorly differentiated LCNEC(approximately 0.5 cm×0.5 cm×0.4 cm),Ki-67(50%),synaptophysin+,and chromogranin A+.dCCA pathology suggested moderately differentiated adenocarcinoma.The patient eventually developed lymph node metastasis in the liver,bone,peritoneum,and abdominal cavity and died 24 months after surgery.Gene sequencing methods were used to compare gene mutations in the two primary bile duct tumours.CONCLUSION The prognosis of MiNEN and pure NEC alone is different,and the selection of treatment options needs to be differentiated.

A case of peribiliary cysts accompanying bile duct carcinoma

A rare case of peribiliary cysts accompaying bile duct carcinoma is presented. A 54-year-old man was diagnosed as having lower bile duct carcinoma and peribiliary cysts by diagnostic imaging. He underwent pylorus preserving pancreatoduodenectomy. As for the peribiliary cysts, a course of observation was taken. Over surgery due to misdiagnosis of patients with biliary malignancy accompanied by peribiliary cysts should be avoided.

Concomitant adenosquamous carcinoma and cystadenocarcinoma of the extrahepatic bile duct: A case report

BACKGROUND Infiltrative adenosquamous carcinoma(ASC) of the extrahepatic bile duct is reported infrequently, which is an unusual variant of the ordinary adenocarcinoma. The simultaneous development of ASC and cystadenocarcinoma in the extrahepatic biliary tree is rare. In addition, the accurate preoperative diagnosis of concomitant carcinoma in the multiple biliary trees at an early stage is often difficult. Thus, awareness of the risk of the multiplicity of biliary tumors is perhaps the most important factor in identifying these cases.CASE SUMMARY Here, we report a case of a 63-year-old female with jaundice, who was referred to Shuguang Hospital because of abdominal pain for 1 mo. An abdominal contrastenhanced computed tomography revealed a type I choledochal cyst and intraluminal masses suggestive of adenoma of the common bile duct. In addition,a preoperative diagnosis of a concomitant Klatskin tumor and type I choledochal cyst was made. The patient underwent anti-inflammatory therapy, followed by radical surgery due to hilar cholangiocarcinoma and resection of the choledochal cyst. Examination of the surgical specimen revealed a papillary tumor of the common bile duct, which arose from the malignant transformation of a preexisting cystadenoma. Histologic examination confirmed a special type of cholangiocarcinoma; the tumor in the hilar bile duct was an ASC, whereas the tumor in the common bile duct was a moderately differentiated cystadenocarcinoma. The patient showed rapid deterioration 8 mo after surgery.CONCLUSION Although concomitant ASC and cystadenocarcinoma of the extrahepatic bile duct is difficult to diagnose before surgery, and the prognosis is poor after surgery,surgical resection is still the preferred treatment.

Extrahepatic intraductal ectopic hepatocellular carcinoma:bile duct filling defect

BACKGROUND:Obstructive jaundice caused by an intraductal hepatocellular carcinoma is a rare initial symptom.We report a rare case of an extrahepatic icteric type hepatocellular carcinoma.METHODS:A 75-year-old patient was admitted to our hospital because of obstructive jaundice 3 months after resection of multilocular hepatocellular carcinoma.A postoperative bile leakage was treated by placement of a decompressing stent in the common bile duct.Endoscopic retrograde choledochoscopy showed extended blood clots filling the bile duct system and computed tomography revealed a local swelling in the common extrahepatic bile duct.The level of alpha-fetoprotein(AFP)was only slightly elevated but that of CA19-9 was dramatically increased.Cholangiography showed an intraductal filling defect typical of a cholangiocellular carcinoma.RESULTS:Bile duct brushing cytology showed no cholangiocellular carcinoma but hepatocellular carcinoma cells in the extrahepatic bile duct.An extrahepatic bile duct resection was performed.Histological examination confirmed the diagnosis of extrahepatic intraductal growth of hepatocellular carcinoma.CONCLUSION:Ectopic hepatocellular carcinoma is a rare but important differentially diagnosed of extrahepatic bile duct filling defect.

Prognosis of hepatocellular carcinoma with bile duct tumor thrombus after R0 resection:a matched study

BACKGROUND： Hepatocellular carcinoma （HCC） with bile duct tumor thrombus （BDTT） is rare. The present study aimed to determine post-surgical prognoses in HCC patients with BDTT, as outcomes are currently unclear. METHODS： We compared the prognoses of 110 HCC patients without BDTT （group A） to 22 cases with BDTT （group B）. The two groups were matched in age, gender, tumor etiology, size, number, portal vascular invasion, and TNM stage. Additionally, 28 HCC patients with BDTT were analyzed to identify prognostic risk factors. RESULTS： The 1-, 3-, and 5-year overall survival rates were 90.9%, 66.9%, and 55.9% for group A and 81.8%, 50.0%, and 37.5% for group B, respectively. The median survival time in groups A and B was 68.8 and 31.4 months, respectively （P=0.043）. The patients for group B showed higher levels of serum total bilirubin, alanine aminotransferase and gammaglutamyl transferase, a larger hepatectomy range, and a higher rate of anatomical resection. In subgroup analyses of patients with BDTT who underwent R0 resection, TNM stage Ⅲ-Ⅳ was an independent risk factor for overall survival; these patients had worse prognoses than those with TNM stage Ⅰ-Ⅱ after R0 resection （hazard ratio=6.056, P=0.014）. Besides, univariate and multivariate analyses revealed that non-R0 resection and TNM stage Ⅲ-Ⅳ were independent risk factors for both disease-free survival and overall survival of 28 HCC patients with BDTT. The median overall survival time of patients with BDTT who underwent R0 resection was longer than that of patients who did not undergo R0 resection （31.0 vs 4.0 months, P=0.007）.CONCLUSIONS： R0 resection prolonged survival time in HCC patients with BDTT, although prognosis remains poor. For such patients, R0 resection is an important treatment that determines long-term survival.

Neuroendocrine carcinoma of the extrahepatic bile duct: Case report and literature review

Neuroendocrine carcinoma (NEC) of the extrahepatic bile duct is rare, and only 22 cases have been reported. Only two of these were large-cell NEC (LCNEC); the vast majority were small-cell NEC. Here, we report a third case of LCNEC of the extrahepatic bile duct. A 76-year-old male presented to a local hospital with painless jaundice. Imaging studies revealed a tumor at the hepatic hilum. The patient underwent right hepatic lobectomy, bile duct resection, and cholecystectomy. The resection specimen showed a 5.0-cm invasive neoplasm involving the hilar bile ducts and surrounding soft tissue. Histologically, the tumor consisted of nests of medium to large cells with little intervening stroma. The tumor invaded a large portal vein branch. All four excised lymph nodes were positive for metastasis, and metastatic deposits were also present in the gallbladder wall. The tumor was diffusely positive for synaptophysin and focally positive for chromogranin A. Approximately 70%-80% of the tumor cells were positive for Ki-67, indicating strong proliferative activity. A diagnosis of LCNEC was made. A few bile ducts within and adjacent to the invasive tumor showed dysplasia of the intestinal phenotype and were focally positive for synaptophysin and chromogranin A, suggesting that the dysplastic intestinal-type epithelium played a precursor role in this case. A postoperative computer tomography scan revealed rapid enlargement of the abdominal and retroperitoneal lymph nodes. The patient died 21 d after the operation. NEC of the bile duct is an aggressive neoplasm, and its biological characteristics remain to be better defined.

Non-Epstein-Barr virus associated lymphoepithelioma-like carcinoma of the inferior common bile duct

A carcinoma displaying undifferentiated features with dense lymphoplasmacytic infiltration is defined as a lymphoepithelioma-like carcinoma(LEC),and some of LEC is associated with Epstein-Barr virus(EBV).All of the 13 previously reported cases of LEC of the biliary system were intrahepatic in location.Herein,we describe the first case of LEC of the inferior common bile duct.A 68-year-old Japanese man,who had been previously treated for hepatocellular carcinoma using microwave coagulation therapy,was found to have tumors of the common bile duct and pancreas head.Histopathological study of the resected tumor showed solid or cohesive nests of large undifferentiated cells with irregular large vesicular nuclei and nucleoli.Around the tumor cell nests,dense lymphoplasmacytic infiltration was observed.Focal glandular differentiation(approximately 5%) was also present.These histopathological features corresponded morphologically to LEC.Immunohistochemically,the tumor cells were positive for cytokeratin(CK) 7,CK 19 and CA19-9,but negative for CK 20 and Hep Par 1.In situ hybridization for Epstein Barr virus early small RNAs disclosed no nuclear signal in tumor cells.Therefore,a diagnosis of non-EBV-associated LEC of the inferior common bile duct was made.Although the prognosis of the biliary LEC is thought to be better than that of conventional cholangiocarcinoma,the differences in prognosis between EBV-positive and-negative cases have not yet been established.Therefore,additional case studies will be needed to clarify the clinicopathological features of LEC of the biliary tract.

Surgical treatment of hepatocellular carcinoma with bile duct tumor thrombi

AIM: To study the surgical treatment effect and outcome of hepatocellular carcinoma (HCC) with bile duct tumor thrombi (BDTT). METHODS: Fifty-three consecutive HCC patients with BDTT admitted in our department from July 1984 to December 2002 were reviewed retrospectively. The clinical data, diagnostic methods, surgical procedures and outcome of these patients were collected and analyzed. RESULTS: One patient rejected surgical treatment, 6 cases underwent percutaneous transhepatic cholangial drainage (PTCD) for unresectable primary disease, and the other 46 cases underwent surgical operation. The postoperative mortality was 17.6%, and the morbidity was 32.6%. Serum total bilirubin levels of these patients with obstructive jaundice decreased gradually after surgery. The survival time of six cases who underwent PTCD ranged from 2 to 7 mo (median survival of 3.7 mo). The survival time of the patients who received surgery was as follows: 2 mo for one patient who underwent laparotomy, 5-46 mo (median survival of 23.5 mo, which was the longest survival in comparison with patients who underwent other procedures, P=0.0024) for 17 cases who underwent hepatectomy, 5-17 mo (median survival of 10.0 mo) for 5 cases who underwent HACE, 3-9 mo (median survival of 6.1 mo) for 11 cases who underwent simple thrombectomy and biliary drainage, and 3-8 mo (median survival of 4.3 mo) for four cases who underwent simple biliary drainage. CONCLUSION: Jaundice caused by BDTT in HCC patients is not a contraindication for surgery. Only curative resection can result in long-term survival. Early diagnosis and surgical treatment are the key points to prolong the survival of patients.

Correlation of glycosyltransferases mRNA expression in extrahepatic bile duct carcinoma with clinical pathological characteristics

BACKGROUND: The incidence of extrahepatic bile duct carcinoma (EBDC) has been increasing, especially in aged people, but the glycobiology of the tumor is not elucida- ted. In this study we investigated the expressions of three glycosyltransferases in 35 patients with EBDC and 35 pa- tients with benign biliary duct disease (BBDD) as well as their clinicopathological significance. METHOD: The patients were divided into several sub- groups by tumor differentiation, TNM stage, and invasion by the standards recommended by UICC. Tumor samples were immediately frozen in liquid nitrogen after resection, followed by mRNA determination of enzymes in the tissue using a mRNA selective reverse trancriptase-polymerase chain reaction kit. The mRNA levels of different groups were semi-quantitatively compared. RESULTS: The mRNA levels of N-acetylglucosaminyltrans- ferase V (GnT-V) and a subtype of α2,3 sialyltransferases for N-glycans, ST3Gal- were elevated 7.75 and 5.39 times in EBDC as compared with BBDD, respectively, and they were correlated to several clinicopathological factors including tumor advancement, differentiation, metastasis, and invasiveness. The mRNA expression of another sialyl- transferase, ST6Gal- , was also 0.63-fold higher in EBDC than in BBDD, but not involved in the clinicopathological characteristics. CONCLUSION: The elevated expression of these three gly- cosyltransferases can be considered as an important molecu- lar event in the occurrence and progression of EBDC.

Impact of lymph node micrometastasis in hilar bile duct carcinoma patients

AIM- To immunohistochemicaUy examine micrometastasis and VEGF-C expression in hilar bile duct carcinoma （HBDC） and to evaluate the clinical significance of the results. METHODS： A total of 361 regional lymph nodes from 25 patients with node-negative HBDC were immunostained with an antibody against cytokeratins 8 and 18 （CAM 5.2）, and immunohistochemical staining of VEGF-C was performed in 34 primary resected tumors. RESULTS： Lymph node micrometastasis was detected in 6 （24%） of the 25 patients and 10 （2.8%） of the 361 lymph nodes. Patients with micrometastasis showed significantly poorer survival rates than those without （P= 0.025）. VEGF-C expression was positive in 17 （50%） of 34 HBDC, and significantly correlated with lymph node metastasis （P=0.042） and microscopic venous invasion （P=0.035）. CONCLUSIONS： It is suggested that immunohistochemically detected lymph node micrometastasis has an impact on the outcome of HBDC. VEGF-C expression is highly correlated with lymph node metastasis in HBDC and might therefore be a useful predictor.

Primary large cell neuroendocrine carcinoma in the common bile duct:First Asian case report

Large cell neuroendocrine carcinoma (LCNEC) in the biliary system is a poorly differentiated, high-grade neuroendocrine tumor. These tumors exhibit aggressive behavior and an increased tendency for early nodal and distant metastases. Herein, we report an unusual case of a pure primary LCNEC of the common bile duct (CBD). A 75-year-old female presented with nausea and jaundice. The patient underwent a CBD excision with lymph node dissection. Upon histological and immunohistochemical examination, the tumor exhibited pure large cell-type neuroendocrine features. Metastases were noted in two of the eight lymph nodes. The patient was administered adjuvant chemotherapy. The patient&#x02019;s cancer recurred 7 mo after surgery, and the patient died from liver failure 5 mo after recurrence. The prognosis of LCNEC of CBD remains poor despite curative resection and adjuvant chemotherapy. The role of additional therapies, such as multimodal treatment including radiation therapy, must be further studied to improve the prognoses of patients.

Hepatocellular carcinoma with tumor thrombus in bile duct:A proposal of new classification according to resectability of primary lesion

BACKGROUND Hepatocellular carcinoma(HCC)with tumor thrombus in the bile duct(BDTT)is easily misdiagnosed or mistreated due to the clinicopathological diversity of the thrombus and its relationship with primary lesions.AIM To propose a new classification for HCC with BDTT in order to guide its diagnosis and treatment.METHODS A retrospective review of the diagnosis and treatment experience regarding seven typical HCC patients with BDTT between January 2010 and December 2019 was conducted.RESULTS BDTT was preoperatively confirmed by computed tomography/magnetic resonance imaging in only four patients.Three patients with recurrent HCC and one patient with first-occurring HCC had no visible intrahepatic tumors;of these,misdiagnosis occurred in two patients,and three patients died.One patient was mistreated as having common bile duct stones,and another patient with a history of multiple recurrent HCC was misdiagnosed until obvious biliary dilation could be detected.Only one patient who received hepatectomy accompanied by BDTT extraction exhibited disease-free survival during the follow-up period.A new classification was proposed for HCC with BDTT as follows:HCC with microscopic BDTT(Type Ⅰ);resectable primary or recurrent HCC mass in the liver with BDTT(Type Ⅱ);BDTT without an obvious HCC mass in the liver(Type Ⅲ)and BDTT accompanied with unresectable intra-or extrahepatic HCC lesions(Type Ⅳ).CONCLUSION We herein propose a new classification system for HCC with BDTT to reflect its pathological characteristics and emphasize the significance of primary tumor resectability in its treatment.

Neuroendocrine carcinoma of the extrahepatic bile duct: A case report

Neuroendocrine carcinoma(NEC) originating from the gastrointestinal hepatobiliary-pancreas is a rare, invasive, and progressive disease, for which the prognosis is extremely poor. The patient was a 72-year-old man referred with complaints of jaundice. He was diagnosed with middle extrahepatic cholangiocarcinoma(cT 4N1M0, c Stage Ⅳ). He underwent a right hepatectomy combined with extrahepatic bile duct and portal vein resection after percutaneous transhepatic portal vein embolization. Microscopic examination showed a large-cell neuroendocrine carcinoma according to the WHO criteria for the clinicopathologic classification of gastroenteropancreatic neuroendocrine tumors. Currently, the patient is receiving combination chemotherapy with cisplatin and etoposide for postoperative multiple liver metastases. Although NEC is difficult to diagnose preoperatively, it should be considered an uncommon alternative diagnosis.

Thermo-chemo-radiotherapy for advanced bile duct carcinoma

AIM： Complete resection of the bile duct carcinoma is sometimes difficult by subepithelial spread in the duct wall or direct invasion of adjacent blood vessels. Nonresected extrahepatic bile duct carcinoma has a dismal prognosis,with a life expectancy of about 6 mo to i year. To improve the treatment results of locally advanced bile duct carcinoma, we have been conducting a clinical trial using regional hyperthermia in combination with chemoradiation therapy.METHODS： Eight patients complaining of obstructive jaundice with advanced extrahepatic bile duct underwent thermo-chemo-radiotherapy （TCRT）. All tumors were located in the upper bile duct and involved hepatic bifurcation, and obstructed the bile duct completely.Radiofrequency capacitive hyperthermia was administered simultaneously with chemotherapeutic agents once weekly immediately following radiotherapy at 2 Gy.We administered heat to the patient for 40 rain after the tumor temperature had risen to 42℃. The chemotherapeutic agents employed were cis-platinum （CDDP,50 mg/m^2） in combination with 5-fluorouracil （5-FU,800 mg/m^2） or methotrexate （MTX, 30 mg/m^2） in combination with 5-FU （800 mg/m^2）. Number of heat treatments ranged from 2 to 8 sessions. The bile duct at autopsy was histologically examined in three patients treated with TCRT.RESULTS： In respect to resolution of the bile duct, there were three complete regression （CR）, two partial regression （PR）, and three no change （NC）. Mean survival was 13.2＋10.8 mo （mean＋SD）. Four patients survived for more than 20 too. Percutaneous transhepatic biliary drainage （PTBD） tube could be removed in placement of self-expandable metallic stent into the patency-restored bile duct after TCRT. No major side effects occurred. At autopsy, marked hyalinization or fibrosis with necrosis replaced extensively bile duct tumor and wall, in which suppressed cohesiveness of carcinoma cells and degenerative cells were sparsely observed.CONCLUSION： Although the number of cases is rather small, TCRT in the treatment of locally advanced bile duct carcinoma is promising in raising local control and thus,long-term survival.