Prognostic factors in patients with middle and distal bile duct cancers

AIM: To identify the influence of the surgery type and prognostic factors in middle and distal bile duct cancers.

Effect of preoperative biliary drainage on surgical results after pancreaticoduodenectomy in patients with distal common bile duct cancer:Focused on the rate of decrease in serum bilirubin

AIM: To examine if the rate of decrease in serum bilirubin after preoperative biliary drainagecan be used as a predicting factor for surgical complications and postoperative recovery after pancreaticoduodenectomy in patients with distal common bile duct cancer.METHODS: A retrospective study was performed in 49 consecutive patients who underwent pancrea-ticoduodenectomy for distal common bile duct cancer. Potential risk factors were compared between the complicated and uncomplicated groups. Also, the rates of decrease in serum bilirubin were compared pre- and postoperatively. RESULTS: Preoperative biliary drainage (PBD) was performed in 40 patients (81.6%). Postoperative morbidity and mortality rates were 46.9% (23/49) and 6.1% (3/49), respectively. The presence or absence of PBD was not different between the complicated and uncomplicated groups. In patients with PBD, neither the absolute level nor the rate of decrease in serum bilirubin was significantly different. Patients with rapid decrease preoperatively showed faster decrease during the first postoperative week (5.5 ± 4.4 μmol/L vs -1.7 ± 9.9 μmol/L, P = 0.004).CONCLUSION: PBD does not affect the surgical outcome of pancreaticoduodenectomy in patients with distal common bile duct cancer. There is a certain group of patients with a compromised hepatic excretory function, which is represented by the slow rate of decrease in serum bilirubin after PBD.

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 Review of Type 1 and Type 2 Intraductal Papillary Neoplasms of the Bile Duct

Intraductal papillary neoplasm of the bile duct(IPNB)is a heterogeneous disease similar to intraductal papillary mucinous neoplasm of the pancreas.These lesions have been recognized as one of the three major precancerous lesions in the biliary tract since 2010.In 2018,Japanese and Korean pathologists reached a consensus,classifying IPNBs into type l and type 2 IPNBs.IPNBs are more prevalent in male patients in East Asia and are closely related to diseases such as cholelithiasis and schistosomiasis.From a molecular genetic perspective,IPNBs exhibit early genetic variations,and different molecular pathways may be involved in the tumorigenesis of type 1 and type 2 IPNBs.The histological subtypes of IPNBs include gastric,intestinal,pancreaticobiliary,or oncocytic subtypes,but type 1 IPNBs typically exhibit more regular and well-organized histological features than type 2 IPNBs and are more commonly found in the intrahepatic bile ducts with abundant mucin.Due to the rarity of these lesions and the absence of specific clinical and laboratory features,imaging is crucial for the preoperative diagnosis of IPNB,with local bile duct dilation and growth along the bile ducts being the main imaging features.Surgical resection remains the optimal treatment for IPNBs,but negative bile duct margins and the removal of lymph nodes in the hepatic hilum significantly improve the postoperative survival rates for patients with IPNBs.

Endoscopic ultrasound-guided vs endoscopic retrograde cholangiopancreatography biliary drainage for obstructed distal malignant biliary strictures: A systematic review and meta-analysis

BACKGROUND For palliation of malignant biliary obstruction(MBO), the gold-standard method of biliary drainage is endoscopic retrograde cholangiopancreatography(ERCP)with the placement of metallic stents. Endoscopic ultrasound(EUS)-guided drainage is an alternative that is typically reserved for cases of ERCP failure.Recently, however, there have been robust randomized clinical trials(RCTs)comparing EUS-guided drainage and ERCP as primary approaches to MBO.AIM To compare EUS guidance and ERCP in terms of their effectiveness and safety in palliative biliary drainage for MBO.METHODS This was a systematic review and meta-analysis, in which we searched the MEDLINE, Excerpta Medica, and Cochrane Central Register of Controlled Trials databases. Only RCTs comparing EUS and ERCP for primary drainage of MBO were eligible. All of the studies selected provided data regarding the rates of technical and clinical success, as well as the duration of the procedure, adverse events, and stent patency. We assessed the risk of biases using the Jadad score and the quality of evidence using the Grading of Recommendations Assessment,Development and Evaluation criteria.RESULTS The database searches yielded 5920 records, from which we selected 3 RCTs involving a total of 222 patients(112 submitted to EUS and 110 submitted to ERCP). In the EUS and ERCP groups, the rate of technical success was 91.96%n and 91.81%, respectively, with a risk difference(RD) of 0.00%(95%CI:-0.07, 0.07;P = 0.97; I^2 = 0%). The clinical success was 84.81% and 85.53% in the EUS and ERCP groups, respectively, with an RD of-0.01%(95%CI:-0.12, 0.10; P = 0.90; I^2 =0%). The mean difference(MD) for the duration of the procedure was-0.12%(95%CI:-8.20, 7.97; P = 0.98; I^2 = 84%). In the EUS and ERCP groups, there were14 and 25 adverse events, respectively, with an RD of-0.06%(95%CI:-0.23, 0.12; P= 0.54; I^2 = 77%). The MD for stent patency was 9.32%(95%CI:-4.53, 23.18; P =0.19; I^2 = 44%). The stent dysfunction rate was significantly lower in the EUS t group(MD =-0.22%; 95 CI:-0.35,-0.08; P = 0.001; I^2 = 0%).CONCLUSION EUS represents an interesting alternative to ERCP for MBO drainage,demonstrating lower stent dysfunction rates compared with ERCP. Technical and clinical success, duration, adverse events and patency rates were similar.

Effectiveness of a new approach to minimally invasive surgery in palliative treatment of patients with distal malignant biliary obstruction

BACKGROUND Palliative endoscopic biliary drainage is the primary treatment option for the management of patients with jaundice which results from distal malignant biliary obstruction(DMBO).In this group of patients,decompression of the bile duct(BD)allows for pain reduction,symptom relief,chemotherapy administration,improved quality of life,and increased survival rate.To reduce the unfavorable effects of BD decompression,minimally invasive surgical techniques require continuous improvement.AIM To develop a technique for internal-external biliary-jejunal drainage(IEBJD)and assess its effectiveness in comparison to other minimally invasive procedures in the palliative treatment of patients with DMBO.METHODS A retrospective analysis of prospectively collected data was performed,which included 134 patients with DMBO who underwent palliative BD decompression.Biliary-jejunal drainage was developed to divert bile from the BD directly into the initial loops of the small intestine to prevent duodeno-biliary reflux.IEBJD was carried out using percutaneous transhepatic access.Percutaneous transhepatic biliary drainage(PTBD),endoscopic retrograde biliary stenting(ERBS),and internal-external transpapillary biliary drainage (IETBD) were used for the treatment of studypatients. Endpoints of the study were the clinical success of the procedure, the frequency andnature of complications, and the cumulative survival rate.RESULTSThere were no significant differences in the frequency of minor complications between the studygroups. Significant complications occurred in 5 (17.2%) patients in the IEBJD group, in 16 (64.0%)in the ERBS group, in 9 (47.4%) in the IETBD group, and in 12 (17.4%) in the PTBD group.Cholangitis was the most common severe complication. In the IEBJD group, the course ofcholangitis was characterized by a delayed onset and shorter duration as compared to other studygroups. The cumulative survival rate of patients who underwent IEBJD was 2.6 times higher incomparison to those of the PTBD and IETBD groups and 20% higher in comparison to that of theERBS group.CONCLUSIONIEBJD has advantages over other minimally invasive BD decompression techniques and can berecommended for the palliative treatment of patients with DMBO.

Percutaneous transhepatic cholangioscopy-assisted biliary polypectomy for local palliative treatment of intraductal papillary neoplasm of the bile duct

BACKGROUND Intraductal papillary neoplasm of the bile duct(IPNB)is a premalignant biliarytype epithelial neoplasm with intraductal papillary or villous growth.Currently reported local palliative therapeutic modalities,including endoscopic nasobiliary drainage,stenting and biliary curettage,endoscopic biliary polypectomy,percutaneous biliary drainage,laser ablation,argon plasma coagulation,photodynamic therapy,and radiofrequency ablation to relieve mechanical obstruction are limited with weaknesses and disadvantages.We have applied percutaneous transhepatic cholangioscopy(PTCS)-assisted biliary polypectomy(PTCS-BP)technique for the management of IPNB including mucin-hypersecreting cast-like and polypoid type tumors since 2010.AIM To assess the technical feasibility,efficacy,and safety of PTCS-BP for local palliative treatment of IPNB.METHODS Patients with mucin-hypersecreting cast-like or polypoid type IPNB and receiving PTCS-BP between September 2010 and December 2019 were included.PTCS-BP was performed by using a half-moon type snare with a soft stainless-steel wire,and the tumor was snared and resected with electrocautery.The primary outcome was its feasibility,indicated by technical success.The secondary outcomes were efficacy,including therapeutic success,curative resection,and clinical success,and safety.RESULTS Five patients(four with mucin-hypersecreting cast-like type and one with polypoid type IPNB)were included.Low-and high-grade intraepithelial neoplasia(HGIN)and recurrent IPNB with invasive carcinoma were observed in one,two,and two patients,respectively.Repeated cholangitis and/or obstructive jaundice were presented in all four patients with mucin-hypersecreting cast-like type IPNB.All five patients achieved technical success of PTCS-BP.Four patients(three with mucin-hypersecreting cast-like type and one with polypoid type IPNB)obtained therapeutic success;one with mucin-hypersecreting cast-like type tumors in the intrahepatic small bile duct and HGIN had residual tumors.All four patients with mucin-hypersecreting IPNB achieved clinical success.The patient with polypoid type IPNB achieved curative resection.There were no PTCS-BP-related serious adverse events.CONCLUSION PTCS-BP appears to be feasible,efficacious,and safe for local palliative treatment of both mucin-hypersecreting cast-like and polypoid type IPNB.

Simultaneous intraductal papillary neoplasms of the bile duct and pancreas treated with chemoradiotherapy

Some authors have suggested that intraductal papillary mucinous neoplasms of the bile duct(IPMN-B) could be the the biliary counterpart of IPMN of the pancreas(IPMN-P) since they share several clinical-pathological features.These include prominent intraductal papil-lary proliferation pattern,a gastrointestinal phenotype,frequent mucin hyper-secretion and progression to mu-cinous carcinoma.To date there are just four reported cases of patients with synchronous IPMN-B and IPMN-P all of which were treated surgically.We hereby report the case of a 76-year-old woman who was incidentally diagnosed with both an asymptomatic 3 cm bulky uid lesion obstructing the bile duct lumen,diagnosed as a malignant IPMN-B,and synchronous multiple pancreatic cystic lesions(10-13 mm) communicating with an irreg-ular Wirsung,diagnosed as branch duct IPMN-P.Since surgery was ruled-out because of the patient's age and preferences,she underwent a conservative manage-ment regimen comprising both chemotherapy and radio-therapy.This was effective in decreasing the mass size and in resolving subsequent jaundice.This is also the f irst reported case of IPMN-B successfully treated with chemoradiotherapy.Clinicians should consider medical treatment as an option in this clinical scenario,in pa-tients who may be unf it for surgery.

Gd-EOB-DTPA-enhanced magnetic resonance imaging for bile duct intraductal papillary mucinous neoplasms

AIM: To investigate gadolinium-ethoxybenzyldiethylenetriamine-pentaacetic acid(Gd-EOB-DTPA)-enhanced magnetic resonance imaging(MRI) of intraductal papillary mucinous neoplasms of the bile duct(IPMN-B). METHODS: The imaging findings of five cases of IPMN-B which were pathologically confirmed at our hospital between March 2012 and May 2013 were retrospectively analyzed. Three of these cases were diagnosed by duodenal endoscopy and biopsy pathology, and two cases were diagnosed by surgical pathology. All five patients underwent enhanced and non-enhanced computed tomography(CT), magnetic resonance cholangiopancreatography, and Gd-EOB-DTPA-enhanced MRI; one case underwent both Gd-EOB-DTPA-enhanced MRI and positron emission tomography-CT. The clinical data and imaging results for these cases were compared and are presented.RESULTS: Conventional imaging showed diffusedilatation of bile ducts and multiple intraductal polypoid and papillary neoplasms or serrated changes along the bile ducts. In two cases, Gd-EOB-DTPA-enhanced MRI revealed dilated biliary ducts and intraductal tumors, as well as filling defects caused by mucin in the dilated bile ducts in the hepatobiliary phase. GdEOB-DTPA-enhanced MRI in one case clearly showed a low-signal tumor in the hepatobiliary phase, similar to what was seen by positron emission tomographyCT. In two patients, routine inspection was unable to discern whether the lesions were inflammation or tumors. However, Gd-EOB-DTPA-enhanced MRI revealed a pattern of gradual enhancement during the hepatobiliary phase, and the signal intensity of the lesions was lower than the surrounding liver parenchyma, suggesting tissue inflammation in both cases, which were confirmed by surgical pathology. CONCLUSION: Gd-EOB-DTPA-enhanced MRI reveals the intraductal mucin component of IPMN-B in some cases and the extent of tumor infiltration beyond the bile ducts in invasive cases.

Surgically treating a rare and asymptomatic intraductal papillary neoplasm of the bile duct:A case report

BACKGROUND Intraductal papillary neoplasms of the bile duct(IPNBs)are rare and characterized by papillary growth within the bile duct lumen.IPNB is similar to obstructive biliary pathology.In this report,we present an unexpected case of asymptomatic IPNB and consolidate our findings with the relevant literature to augment our understanding of this condition.Integrating relevant literature contributes to a more comprehensive understanding of the disease.CASE SUMMARY A 66-year-old Chinese male patient was admitted to our hospital for surgical intervention after gallstones were discovered during a routine physical examination.Preoperative imaging revealed a lesion on the left side of the liver,which raised the suspicion of IPNB.A laparoscopic left hemihepatectomy was performed,and subsequent histopathological examination confirmed the diagnosis of IPNB.At the 3-mo postoperative follow-up,the patient reported good recovery and no metastasis.IPNB can manifest both latently and asymptomatically.Radical surgical resection is the most effective treatment for IPNB.CONCLUSION Hepatic and biliary masses,should be considered to diagnose IPNB.Prompt surgery and vigilant follow-up are crucial in determining prognosis.

Epidemiology and outcome of individuals with intraductal papillary neoplasms of the bile duct

BACKGROUND Intraductal papillary neoplasm of the bile duct(IPNB)is a rare distinct subtype of precursor lesions of biliary carcinoma.IPNB is considered to originate from luminal biliary epithelial cells,typically displays mucin-hypersecretion or a papillary growth pattern,and results in cystic dilatation[1].IPNB develops anywhere in the intrahepatic and extrahepatic biliary tracts,and can occur in various pathological stages from low-grade dysplasia to invasive carcinoma.IPNBs have similar phenotypic changes in the occurrence and development of all subtypes,and the prognosis is significantly better than that of traditional(nonpapillary)cholangiocarcinoma.AIM To evaluate the clinicopathological features of IPNB to provide evidence-based guidance for treatment.METHODS Invasive IPNB,invasive intraductal papillary mucinous neoplasm of the pancreas(IPMN),and traditional cholangiocarcinoma data for affected individuals from 1975 to 2016 were obtained from the Surveillance,Epidemiology,and End Results(SEER)database.Annual percentage changes(APCs)in the incidence and incidence-based(IB)mortality were calculated.We identified the independent predictors of overall survival(OS)and cancer-specific survival(CSS)in indivi duals with invasive IPNB.RESULTS The incidence and IB mortality of invasive IPNB showed sustained decreases,with an APC of-4.5%(95%CI:-5.1%to-3.8%)and-3.3%(95%CI:-4.1%to-2.6%)(P<0.001),respectively.Similar decreases in incidence and IB mortality were seen for invasive IPMN but not for traditional cholangiocarcinoma.Both OS and CSS for invasive IPNB were better than for invasive IPMN and traditional cholangiocarcinoma.A total of 1635 individuals with invasive IPNB were included in our prognosis analysis.The most common tumor sites were the pancreaticobiliary ampulla(47.9%)and perihilar tract(36.7%),but the mucin-related subtype of invasive IPNB was the main type,intrahepatically(approximately 90%).In the univariate and multivariate Cox regression analysis,age,tumor site,grade and stage,subtype,surgery,and chemotherapy were associated with OS and CSS(P<0.05).CONCLUSION Incidence and IB mortality of invasive IPNB trended steadily downward.The heterogeneity of IPNB comprises site and the tumor’s mucin-producing status.

Simultaneous liver mucinous cystic and intraductal papillary mucinous neoplasms of the bile duct:A case report

Cystic hepatic neoplasms are rare tumors,and are classified into two separate entities:mucinous cystic neoplasms(MCNs)and intraductal papillary mucinous neoplasms of the bile duct(IPMN-B).We report the case of a 56-year-old woman who presented with abdominal pain and jaundice due to the presence of a large hepatic multilocular cystic tumor associated with an intraductal tumor.Partial hepatectomy with resection of extrahepatic bile ducts demonstrated an intrahepatic MCN and an intraductal IPMN-B.This is the first report of the simultaneous occurrence of these two histologically distinct entities in the liver.

Common bile duct lesions-how cholangioscopy helps rule out intraductal papillary neoplasms of the bile duct:A case report

BACKGROUND Intraductal papillary neoplasm of the bile duct(IPNB)is a rare variant of bile duct tumors,characterized by an exophytic growth exhibiting a papillary mass within the bile duct lumen and it can be localized anywhere along the biliary tree,with morphological variations and occasional invasion.CASE SUMMARY We present a patient with obstructive jaundice who was diagnosed with IPNB using cholangioscopy during endoscopic retrograde cholangio-pancreatography.Using the SpyGlass DS Ⅱ technology,we were able to define tumor extension and obtain targeted Spy-byte biopsies.After multidisciplinary evaluation,the patient was scheduled for surgical resection of the tumor,which was radically removed.CONCLUSION Cholangioscopy appears to be crucial for the rapid and clear diagnosis of lesions in the bile duct to achieve radical surgical resection.

Successful endoscopic treatment of an intraductal papillary neoplasm of the bile duct

We present a case of a 76-year-old man with right upper quadrant abdominal pain and weight loss,who was found to have an intraductal papillary neoplasm of the bile duct(IPNB)of the pancreaticobiliary subtype,deemed curatively resectable.The patient declined surgery and opted for endoscopic therapy.He underwent two sessions of endoscopic retrograde cholangiopancreatography(ERCP)-guided radiofrequency ablation(RFA).Ten months later,no evidence of recurrence was identified on repeat ERCP.To our knowledge,this is the first reported case of successful use of RFA as a primary treatment modality for resectable IPNB.

Intraductal papillary neoplasm of the bile duct:The new frontier of biliary pathology

Intraductal papillary neoplasms of the bile duct(IPNBs)represent a rare variant of biliary tumors characterized by a papillary growth within the bile duct lumen.Since their first description in 2001,several classifications have been proposed,mainly based on histopathological,radiological and clinical features,although no specific guidelines addressing their management have been developed.Bile duct neoplasms generally develop through a multistep process,involving different precursor pathways,ranging from the initial lesion,detectable only microscopically,i.e.biliary intraepithelial neoplasia,to the distinctive grades of IPNB until the final stage represented by invasive cholangiocarcinoma.Complex and advanced investigations,mainly relying on magnetic resonance imaging(MRI)and cholangioscopy,are required to reach a correct diagnosis and to define an adequate bile duct mapping,which supports proper treatment.The recently introduced subclassifications of types 1 and 2 highlight the histopathological and clinical aspects of IPNB,as well as their natural evolution with a particular focus on prognosis and survival.Aggressive surgical resection,including hepatectomy,pancreaticoduodenectomy or both,represents the treatment of choice,yielding optimal results in terms of survival,although several endoscopic approaches have been described.IPNBs are newly recognized preinvasive neoplasms of the bile duct with high malignant potential.The novel subclassification of types 1 and 2 defines the histological and clinical aspects,prognosis and survival.Diagnosis is mainly based on MRI and cholangioscopy.Surgical resection represents the mainstay of treatment,although endoscopic resection is currently applied to nonsurgically fit patients.New frontiers in genetic research have identified the processes underlying the carcinogenesis of IPNB,to identify targeted therapies.

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.

Study on variou operations and prognosis extrahepatic bile duct cance

AIMS To evaluate clinically the surgical procedures and their in- fluence on the prognosis of extrahepatic bile duct cancer. METHODS A total of 55 patients with pathologically and clini- cally verified extrahepatic bile duct cancer treated in our depart- ment between January 1984 and December 1993 were retrospec- tively analyzed.Clinical courses with respect to the surgical pro- cedures employed and the survival period of these patients were followed up and compared. RESLUTS Of these patients,24 involved the upper third of ex- trahepatic biliary tract,12 the middle third,and 19 the lower third.Diagnosis of bile duct cancer was confirmed histopatholo- gically in 42 patients,with a clear predominance of adenocarcino- ma(97.6 percent).Eleven(26.2 percent)patients received cu- rative resection;30 received palliative procedures,i.e.,biliary- enteric bypass(n=14)and external drainage(n=16);6 re- ceived permanent PTCD alone and 8 received exploratory laparo- tomy only or conservative treatment.Forty-eight patients(87.3 percent)were followedup.The overall mean survival period was 10.8±9.7months(±s);patients with curative resection had the longest survival period(21.4±16.7 months,±s,P<0. 01)and highest survival rate(P<0.05);a significant survival difference was observed in patients with biliary-enteric anastomo- sis compared with those with external drainage,ect.(P<0. 05);but there was no significant difference in survival period be- tween patients having PTCD(n=23)and not(n=26)prior to surgery(P>0.05). CONCLUSIONS Curactive resection is the treatment of choice for suitable patients with extrahepatic bile duct cancer;biliary-en- teric anastomosis is preferable in those with unresectable tumor in order to improve the prognosis and quality of life.

Intraductal neoplasm of the intrahepatic bile duct: Clinicopathological study of 24 cases

AIM: To investigate the clinicopathological features of intraductal neoplasm of the intrahepatic bile duct (INihB). METHODS: Clinicopathological features of 24 cases of INihB, which were previously diagnosed as biliary papillomatosis or intraductal growth of intrahepatic biliary neoplasm, were reviewed. Mucin immunohistochemistry was performed for mucin (MUC)1, MUC2, MUC5AC and MUC6. Ki-67, P53 and β-catenin immunoreactivity were also examined. We categorized each tumor as adenoma (low grade), borderline (intermediate grade), and malignant (carcinoma in situ , high grade including tumors with microinvasion). RESULTS: Among 24 cases of INihB, we identified 24 tumors. Twenty of 24 tumors (83%) were composed of a papillary structure; the same feature observed in intraductal papillary neoplasm of the bile duct (IPNB). In contrast, the remaining four tumors (17%) showed both tubular and papillary structures. In three of the four tumors (75%), macroscopic mucin secretion was limited but microscopic intracellular mucin was evident. Histologically, 16 tumors (67%) were malignant, three (12%) were borderline, and five (21%) were adenoma. Microinvasion was found in four cases (17%). Immunohistochemical analysis revealed that MUC1 was not expressed in the borderline/adenoma group but was expressed only in malignant lesions (P = 0.0095). Ki-67 labeling index (LI) was significantly higher in the malignant group than in the borderline/adenoma group (22.2 ± 15.5 vs 7.5 ± 6.3, P < 0.01). In the 16 malignant cases, expression of MUC5AC showed borderline significant association with high Ki-67 LI (P = 0.0622). Nuclear expression of β-catenin was observed in two (8%) of the 24 tumors, and these two tumors also showed MUC1 expression. P53 was negative in all tumors. CONCLUSION: Some cases of INihB have a tubular structure, and are subcategorized as IPNB with tubular structure. MUC1 expression in INihB correlates positively with degree of malignancy.

Detection of hepatitis C virus NS5 protein and genome in Chinese carcinoma of the extrahepatic bile duct and its significance

AIM To investigate the hepatitis C virus(HCV)infection in the tissues of carcinoma ofextrahepatic bile duct and study theircorrelation.METHODS HCV NS5 protein and HCV RNA weredetected by labeled streptavidin biotin(LSAB)method and in situ reverse transcriptionpolymerase chain reaction(IS-RT-PCR)insections of 51 cases of carcinoma ofextrahepatic bile duct and 34 cases of controlgroup(without malignant biliary disease).RESULTS In 51 cases of carcinoma ofextrahepatic bile duct,HCV NS5 protein wasdetected in 14(27.5%),which was clearlystained in the cytoplasm of cancer cell but not inthe nucleus or cell membrane.HCV RNA wasdetected in 18(35.4%),which was located inthe nucleus of cancer cell in 12 cases and in thecytoplasm in 6 cases.HCV NS5 protein and RNAcoexistence was found in 2 cases.In 34 cases ofcontrol group,HCV RNA was detected in 2(5.9%).HCV NS5 protein and RNA positive cellswere found either scattered or in clusters.CONCLUSION The prevalence of hepatitis C viral infection in the tissues of carcinoma ofextrahepatic bile duct was significantly higherthan in control group(X^2=9.808,P=0.002).The findings suggest a correlation between HCVinfection and carcinoma of extrahepatic bileduct,which is different from the traditionalviewpoint.HCV infection might be involved inthe development of carcinoma of extrahepaticbile duct.

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.