Overexpression of proteasome 26S subunit non-ATPase 6 protein and its clinicopathological significance in intrahepatic cholangiocarcinoma

BACKGROUND Currently,intrahepatic cholangiocarcinoma(ICC)poses a continuing,significant health challenge,but the relationship has yet to be established between ICC and the proteasome 26S subunit non-ATPase 6(PSMD6).AIM To investigate the protein expression and clinicopathological significance of PSMD6 in ICC.METHODS The potential impact of the PSMD6 gene on the growth of ICC cell lines was analyzed using clustered regularly interspaced short palindromic repeat knockout screening technology.Forty-two paired specimens of ICC and adjacent noncancerous tissues were collected.PSMD6 protein expression was determined by immunohistochemistry.Receiver operating characteristic curve analysis was performed to validate PSMD6 expression level,and its association with ICC patients’various clinicopathological characteristics was investigated.RESULTS The PSMD6 gene was found to be essential for the growth of ICC cell lines.PSMD6 protein was significantly overexpressed in ICC tissues(P<0.001),but showed no significant association with patient age,gender,pathological grade,or tumor-node-metastasis stage(P>0.05).CONCLUSION PSMD6 can promote the growth of ICC cells,thus playing a pro-oncogenic role.

Combined hepatocellular cholangiocarcinoma: A clinicopathological update

Combined hepatocellular-cholangiocarcinoma(cHCC-CCA)is a rare primary liver cancer associated with an appalling prognosis.The diagnosis and manage-ment of this entity have been challenging to physicians,radiologists,surgeons,pathologists,and oncologists alike.The diagnostic and prognostic value of biomarkers such as the immunohistochemical expression of nestin,a progenitor cell marker,have been explored recently.With a better understanding of biology and the clinical course of cHCC-CCA,newer treatment modalities like immune checkpoint inhibitors are being tried to improve the survival of patients with this rare disease.In this review,we give an account of the recent developments in the pathology,diagnostic approach,and management of cHCC-CCA.

Pathological aspects of so called "hilar cholangiocarcinoma"

Cholangiocarcinoma(CC) arising from the large intrahepatic bile ducts and extrahepatic hilar bile ducts share clinicopathological features and have been called hilar and perihilar CC as a group.However,"hilar and perihilar CC" are also used to refer exclusively to the intrahepatic hilar type CC or,more commonly,the extrahepatic hilar CC.Grossly,a major distinction can be made between papillary and non-papillary tumors.Histologically,most hilar CCs are well to moderately differentiated conventional type(biliary) carcinomas.Immunohistochemically,CK7,CK20,CEA and MUC1 are normally expressed,being MUC2 positive in less than 50% of cases.Two main premalignant lesions are known:biliary intraepithelial neoplasia(BilIN) and intraductal papillary neoplasm of the biliary tract(IPNB).IPNB includes the lesions previously named biliary papillomatosis and papillary carcinoma.A series of 29 resected hilar CC from our archives is reviewed.Most(82.8%) were conventional type adenocarcinomas,mostly well to moderately differentiated,although with a broad morphological spectrum;three cases exhibited a poorly differentiated cell component resembling signet ring cells.IPNB was observed in 5(17.2%),four of them with an associated invasive carcinoma.A clear cell type carcinoma,an adenosquamous carcinoma and two gastric foveolar type carcinomas were observed.

Pathological classification of intrahepatic cholangiocarcinoma based on a new concept

Intrahepatic cholangiocarcinoma (ICC) arises from the lining epithelium and peribiliary glands of the intrahepatic biliary tree and shows variable cholangiocytic dif-f-e-re-ntiation. To date-,ICC was large-ly classifie-d into adenocarcinoma and rare variants. Herein,we propose to subclassify the former,based on recent progress in the-study of-ICC including the-gross classification and hepatic progenitor/stem cells and on the pathological similarities between biliary and pancreatic neoplasms. That is,ICC is classifiable into the conventional (bile duct) type,the bile ductular type,the intraductal neoplasm type and rare variants. The conventional type is further divided into the small duct type (peripheral type) and large bile duct type (perihilar type). The former is a tubular or micropapillary adenocarcinoma while the latter involves the intrahepatic large bile duct. Bile ductular type resembles proliferated bile ductules and shows a replacing growth of the hepatic parenchyma.Hepatic progenitor cell or stem cell phenotypes such as neural cell adhesion molecule expression are frequently expressed in the bile ductular type. Intraductal type includes papillary and tubular neoplasms of the bile duct (IPNBs and ITNBs) and a superficial spreading type. IPNB and ITNB show a spectrum from a preneoplastic borderline lesion to carcinoma and may have pancreatic counterparts. At invasive sites,IPNB is associated with the conventional bile duct ICC and mucinous carcinoma. Biliary mucinous cystic neoplasm with ovarian-like stroma in its wall is different from IPNB,particularly IPNB showing cystic dilatation of the affected ducts. Rare variants of ICC include squamous/adenosquamous cell carcinoma,mucinous/signet ring cell carcinoma,clear cell type,undifferentiated type,neuroendocrine carcinoma and so on. This classification of-ICC may ope-n up a ne-w fie-ld of-re-se-arch of-ICC and contribute-to the-clini cal approach to ICC.

Clinicopathologic features, diagnosis and surgical treatment of intrahepatic cholangiocarcinoma in 104 patients

BACKGROUND: The outcome of surgical treatment of pa- tients with intrahepatic cholangiocarcinoma (ICC) is poor. This study was designed to analyze the relationship between clinicopathologic features and the survival time after opera- tion. METHODS: The operation was performed in 104 patients with mass-forming type ICC at our hospital between No- vember 1996 and May 2000. Seventy-nine patients (76.0%) were followed up successfully. Sixteen clinicopathological variables including age, sex, history of chronic liver di- sease , HBsAg, operation, adjuvant therapy, ascites, lymph node metastasis, invasion of adjacent organs, tumor size, necrosis of tumor, envelope, intrahepatic metastasis, Inter- national Union Against Cancer (UICC) TNM staging, his- tology, and cirrhosis were selected for univariate and multi- variate analyses to evaluate their influence on the prognosis. RESULTS: The accumulative 1-, 3-, 5-year survival rates of the 79 patients were 49.4%, 17.3%, 9.6% respectively. Univariate analysis revealed that sex (P=0.0221), HBsAg (P=0.0115), operation (P=0.0042), adjuvant therapy (P= 0.0389), ascites (P=0.0001), invasion (P=0.0220), intra- hepatic metastasis (P=0.0000) and TNM stage (P= 0.0001) were related to survival time. Multivariate analysis revealed that HBsAg, ascites and TNM stage were signifi- cantly related to prognosis. CONCLUSION: Early diagnosis and treatment and major hepatectomy are essential to improving the results of surgi- cal treatment of ICC patients.

Clinicopathological features and prognosis of combined hepatocellular carcinoma and cholangiocarcinoma after surgery

BACKGROUND： Combined hepatocellular carcinoma and cholangiocarcinoma （cHCC-CC） is a rare subtype of primary liver cancer consisting of both hepatocellular carcinoma （HCC） and cholangiocarcinoma （CC）. Because of the rarity of this tumor, its feature is poorly understood. The present study aimed to evaluate the clinicopathological features and long-term prognosis of patients with cHCC-CC after surgery and to compare with those of the patients with stage-matched HCC and CC. METHODS： The dinicopathological features of the patients who underwent surgery for cHCC-CC at our center during the period of 2001-2010 were retrospectively analyzed and compared with those of stage-matched HCC and CC patients. Cancer staging was performed according to the AJCC Cancer Staging Manual （6th ed.）. Overall survival and disease-free survival were compared among the groups and prognostic factors of cHCC-CC were evaluated. RESULTS： Significant differences were observed in clinico- pathological features among 42 patients with cHCC-CC, 90 patients with HCC and 45 patients with CC. Similar to HCC patients, cHCC-CC patients had frequent hepatitis B virus antigen positivity, microscopic vessel invasion, cirrhosis and high level of serum alpha-fetoprotein. Similar to CC patients, cHCC-CC patients showed increased bile duct invasion and decreased capsule. The 1-, 3-, and 5-year overall survival and disease- free survival of patients with cHCC-CC were not significantly different from those with stage-matched patients with CC;but significantly poorer than those with HCC. In subanalysis of patients with stage Ⅱ, the overall survival in patients with cHCC-CC or CC was significantly poorer than that in patients with HCC. We did not find the difference in patients with other stages. Univariate analysis of overall and disease-free survival of patients with cHCC-CC showed that the vascular invasion and intrahepatic metastasis were the significant predictive factors. CONCLUSION： Patients with cHCC-CC showed similar dinico- pathological features as those with HCC or CC, and patients with cHCC-CC or CC had a poorer prognosis compared with those with HCC, especially at matched stage Ⅱ.

Clinicopathological characteristics of 15 patients with combined hepatocellular carcinoma and cholangiocarcinoma

BACKGROUND: Combined hepatocellular carcinoma and cholangiocarcinoma (cHCC-CC) is a rare subtype of primary liver cancer, and clinicopathological features of cHCC-CC have seldom been reported in detail. This study was undertaken to explore the diagnosis and clinicopathological characteristics of cHCC-CC in comparison with hepatocellular carcinoma (HCC) and cholangiocarcinoma (CC), respectively. METHODS: The clinical data from 15 patients with cHCC-CC, 132 patients with HCC and 44 patients with CC who had undergone hepatic resection were analyzed retrospectively. Clinicopathological characteristics of cHCC-CC, HCC and CC such as hepatitis B viral infection, serum hepatitis C virus (HCV) antibody, serum alpha-fetoprotein (AFP) level, cirrhosis, vascular invasion, lymph node metastasis, surgical procedure and adjuvant treatment were also analyzed. Follow up was carried out in the patients, and their 1-, 3-, and 5-year survival rates were calculated. RESULTS: Two patients with cHCC-CC were correctly diagnosed by enhanced CT before operation, the other 13 patients were diagnosed by histology and immunohistochemistry after operation. Radical (8/15) and conservative hepatectomy (7/15) for cHCC-CC was similar to that for HCC and CC (P > 0.05). Pathologically cHCC-CC showed more significantly vascular invasion and lymph node metastasis than HCC (P < 0.05), and a similarity to CC (P > 0.05). Hepatitis B viral infection, serum HCV antibody, cirrhosis, and serum AFP level of cHCC-CC patients were similar to those of HCC patients (P > 0.05) but different from CC patients (P < 0.05). The cumulative 1-, 3-, and 5-year survival rates in patients with cHCC-CC were poorer than in patients with HCC or CC (P < 0.05). CONCLUSIONS: Patients with cHCC-CC are seldom diagnosed before operation. The progression of cHCC-CC is more rapid than that of HCC or CC. Survival rate of patients with cHCC-CC after hepatic resection is poorer than that of patients with HCC or CC.

Clinicopathological analysis of 14 patients with combined hepatocellular carcinoma and cholangiocarcinoma

BACKGROUND:Combined hepatocellular carcinoma and cholangiocarcinoma (cHCC-CC) is an uncommon subtype of primary hepatic carcinoma,and its prognosis is poor.This study was undertaken to investigate the prognosis and the clinicopathological characteristics of cHCC-CC,including their possible cellular origin.METHODS:Among 852 patients with a primary hepatic carcinoma who underwent hepatectomy from January 1998 to April 2008 at our hospital,cHCC-CC was identified in 14 patients The clinicopathological characteristics of the 14 patients were analyzed retrospectively.The expression of the liver stem cell markers (c-kit,CD90,CD133 and CK19) in the tumor tissue was detected by immunohistochemistry,and the Kaplan-Meier method was used to evaluate survival.RESULTS:Among the 14 patients,9 presented with abdominal pain,3 with anorexia and debilitation,and the remaining two patients were asymptomatic.The mean age was 53.6±3.0 (range 38-74) years.Among the included patients,11 had an elevated serum alpha-fetoprotein level,13 were infected with hepatitis B virus,9 had vascular invasion and 1 had lymph node metastasis The average diameter of the tumors was 9.9±1.1 (range 5.0-16.0) cm.The median overall survival time was 7.9±1.0 months In addition,the presence of the liver stem cell markers,c-kit CD90,CD133 and CK19 was 71.4%,85.7%,92.9% and 78.6% respectively.All four markers were simultaneously expressed in eight cases.CONCLUSIONS:cHCC-CC has aggressive characteristics and the prognosis is extremely dismal.The high expression of liver stem cell markers in the tumor tissue suggests that these tumors may derive from liver stem cells.

Management of hilar cholangiocarcinoma in the North of England: Pathology, treatment, and outcome

AIM: To assess the management and outcome of hilar cholangiocarcinoma (Klatskin tumor) in a single tertiary referral center.METHODS: The notes of all patients with a diagnosis of hilar cholangiocarcinoma referred to our unit for over an 8-year period were identified and retrospectively reviewed. Presentation, management and outcome were assessed.RESULTS: Seventy-five patients were identified. The median age was 64 years (range 34-84 years). Male to female ratio was 1:1. Eighty-nine percent of patients presented with jaundice. Most patients referred were under Bismuth classification 3a, 3b or 4. Seventy patients required biliary drainage, 65 patients required 152percutaneous drainage procedures, and 25 had other complications. Forty-one patients had 51 endoscopic drainage procedures performed (15 failed). Of these,36 subsequently required percutaneous drainage. The median number of drainage procedures for all patients was three, 18 patients underwent resection (24%), nine had major complications and three died post-operatively.The 5-year survival rate was 4.2% for all patients, 21%for resected patients and 0% for those who did not undergo resection (P = 0.0021). The median number of admissions after diagnosis in resected patients was two and three in non-resected patients (P＜0.05).Twelve patients had external-beam radiotherapy, seven brachytherapy, and eight chemotherapy. There was no significant benefit in terms of survival (P = 0.46) or hospital admissions.CONCLUSION: Resection increases survival but carries the risk of significant morbidity and mortality.Percutaneous biliary drainage is almost always necessary and endoscopic drainage should be avoided if possible.

Clinicopathological and prognostic analysis of 429 patients with intrahepatic cholangiocarcinoma

AIM:To understand the clinicopathological characteristics and treatment selections and improve survival and provide valuable information for patients with intrahepatic cholangiocarcinoma(ICC). METHODS:We retrospectively evaluated 5311 liver cancer patients who received resection between October 1999 and December 2003.Of these,429(8.1%)patients were diagnosed with ICC,and their clinicopathological, surgical,and survival characteristics were analyzed. RESULTS:Upper abdominal discomfort or pain(65.0%), no symptoms(12.1%),and hypodynamia(8.2%)were the major causes for medical attention.Laboratory tests showed 198(46.4%)patients were HBsAg positive, 90(21.3%)hadα-fetoprotein>20μg/L,50(11.9%) carcinoembryonic antigen>10μg/L,and 242(57.5%) carbohydrate antigen 19-9(CA19-9)>37 U/mL.Survival data was available for 329(76.7%)patients and their mean survival time was 12.4 mo.The overall survival of the patients with R0,R1 resection and punching exploration were 18.3,6.6 and 5.6 mo,respectively. Additionally,CA19-9>37 U/mL was associated with lymph node metastases,but inversely associated withcirrhosis.Multivariate analysis indicated that radical resection,lymph node metastases,macroscopic tumor thrombi and size,and CA19-9 were associated with prognosis. CONCLUSION:Surgical radical resection is still the most effective means to cure ICC.Certain laboratory tests(such as CA19-9)can effectively predict the survival of the patients with ICC.

Etiological and clinicopathologic characteristics of intrahepatic cholangiocarcinoma in young patients

AIM:To investigate the prevalence,risk factors,and clinicopathologic characteristics of intrahepatic cholangiocarcinoma(ICC)in young patients.METHODS:A retrospective analysis was performed in ICC patients referred to the Eastern Hepatobiliary Surgery Hospital in Shanghai,China.Among 317 consecutively enrolled patients,40 patients were aged ≤40 years(12.61%).We compared the risk factors and clinicopathologic characteristics of these patients(groupⅠ:n=40)with those aged>40 years(group Ⅱ:n=277).RESULTS:Group I had distinct features compared with groupⅡ,including a low frequency of hepatolithiasis(P=0.000);a high positive rate of serum hepatitis B surface antigen(P=0.000)and hepatitis B virus(HBV)associated cirrhosis(P=0.038);a high frequency ofα-fetoprotein(>400μg/L)(P=0.011);a low frequency of carbohydrate antigen 19-9(>37 U/mL)(P=0.017);and a high frequency of liver histological inflammation(P=0.002).Although there was no significant difference between the two groups in regards to hepatic schistosomiasis,alcohol-associated cirrhosis and cirrhosis due to other causes(P>0.05),they only occurred in the elderly group.CONCLUSION:The risk factors are significantly different between young and elderly ICC patients.HBV and HBV-associated cirrhosis are the most important risk factors for young ICC patients.

Clinicopathologic significance of slug expression in human intrahepatic cholangiocarcinoma

AIM:To explore the expression and function of slug,a transcriptional repressor,in human intrahepatic cholangiocarcinoma(IHCC)and identify its role in IHCC progression.METHODS:Expression of slug was detected in 36 cases of IHCC and 12 cases of normal intrahepatic bile ducts and liver parenchyma by immunohistochemistry.The patients were divided into low slug expression group(< 20%of carcinoma cells stained)and high slug expression group(≥20%of carcinoma cells stained).Slug expression was correlated with clinicopathological parameters of IHCC patients.The patients were defined as short-term survivors if their survival time was<12 mo and as longterm survivors if their survival time was≥12 mo.RESULTS:Slug was not expressed in normal liver epi-thelium samples,lowly expressed in 15 tissue samples (10-,5+)and highly expressed in 21 tissue samples (16++;5+++)from IHCC patients.The survival rate of patients with a low slug expression was 33.3%(n =5)and 66.7%(n=10),respectively.The survival rate of patients with a high slug expression was 61.9% (n=13)and 38.1%(n=8),respectively(P=0.02).Lymph node metastasis was found in 4(26.7%)out of the 15 patients with a low slug expression and in 14(66.7%)out of the 21 patients with a high slug expression,respectively.The incidence rate of lymph node metastasis increased with the increasing slug expression level(P=0.003),and higher in patients with a high slug expression than in those with a low slug expression.Slug expression did not significantly correlate with the tumor size and stage or histologic grade,or with the gender and age of patients.CONCLUSION:Slug expression is a novel prognostic marker for IHCC with lymph node metastasis.

Histopathological characteristics of needle core biopsy and surgical specimens from patients with solitary hepatocellular carcinoma or intrahepatic cholangiocarcinoma

BACKGROUND Pathological manifestations of hepatic tumours are often associated with prognosis. Although surgical specimens(SS) can provide more information,currently, pre-treatment needle core biopsy(NCB) is increasingly showing important value in understanding the nature of liver tumors and even in diagnosis and treatment decisions. However, the concordance of the clinicopathological characteristics and immunohistochemical(IHC) staining between NCB and SS from patients with hepatic tumours were less concerned.AIM To introduce a more accurate method for interpreting the IHC staining results in order to improve the diagnostic value of hepatic malignancy in NCB samples.METHOD A total of 208 patients who underwent both preoperative NCB and surgical resection for hepatocellular carcinoma(HCC) or intrahepatic cholangiocarcinomaRESULTS Morphologically, the presence of compact tumour nests or a cord-like structure in NCB was considered the primary cause of misdiagnosis of HCC from ICC. The kappa statistic showed a moderate agreement in histomorphology(k = 0.504) and histological grade(k = 0.488) between NCB and SS of the tumours. A 4-tier(+++,++, +, and-) scoring scheme that emphasized the focal neoplastic cell immunoreactivity of tumour cells revealed perfect concordance of CK19, GPC3 and HepPar1 between NCB and SS(k = 0.717; k = 0.768; k = 0.633). Furthermore,with the aid of a binary classification derived from the 4-tier score, a high concordance was achieved in interpreting the IHC staining of the three markers between NCB and final SS(k = 0.931; k = 0.907; k = 0.803), increasing the accuracy of NCB diagnosis C(k = 0.987; area under the curve = 0.997, 95%CI: 0.990-1.000; P< 0.001).CONCLUSION These findings imply that reasonable interpretation of IHC results in NCB is vital for improving the accuracy of tumour diagnosis. The simplified binary classification provides an easy and applicable approach.

Clinicopathologic characteristics of intrahepatic cholangiocarcinoma in patients with positive serum a-fetoprotein

AIM:To explore clinicopathologic characteristics of intrahepatic cholangiocarcinoma (ICC) in patients with positive serum a-fetoprotein (AFP). METHODS:One hundred and thirty one patients who underwent surgical dissection for pathologically confirmed ICC were divided into a positive AFP (> 20 ng/mL) group (n = 32) and a negative AFP group (n = 99), whose clinicopathologic features were analyzed and compared. RESULTS:The positive rate of HBsAg and liver cirrhosis of the positive AFP group was higher than that of the negative AFP group, while the positive rate of CA19-9 (> 37 U/mL) and the lymph node metastasis rate was lower. CONCLUSION:ICC patients with positive AFP share many clinicopathologic similarities with hepatocellular carcinoma.

Pathological,molecular,and clinical characteristics of cholangiocarcinoma:A comprehensive review

Cholangiocarcinomas are a heterogeneous group of highly aggressive cancers that may arise anywhere within the biliary tree.There is a wide geographical variation with regards to its incidence,and risk-factor associations which may include liver fluke infection,primary sclerosing cholangitis,and hepatolithiasis amongst others.These tumours are classified into intrahepatic,perihilar and distal based on their anatomical location.Morphologically,intrahepatic cholangiocarcinomas are further sub-classified into small and large duct variants.Perihilar and distal cholangiocarcinomas are usually mucin-producing tubular adenocarcinomas.Cholangiocarcinomas develop through a multistep carcinogenesis and are preceded by dysplastic and in situ lesions.While clinical characteristics and management of these tumours have been extensively elucidated in literature,their ultra-structure and tumour biology remain relatively unknown.This review focuses on the current knowledge of pathological characteristics,molecular alterations of cholangiocarcinoma,and its precursor lesions(including biliary intraepithelial neoplasia,intraductal papillary neoplasms of the bile duct,intraductal tubulopapillary neoplasms and mucinous cystic neoplasm).

Reduced expression of P120 catenin in cholangiocarcinoma correlated with tumor clinicopathologic parameters

AIM： To investigate the relationship between the expression of P120 and the clinicopathologic parameters in intrahepatic cholangiocarcinoma （ICC）. METHODS： An immunohistochemical study of E-cadherin and P120 catenin was performed on 42 specimens of ICC with a Dako Envision kit. RESULTS： The expression of E-cadherin and P120 was reduced in 27 cases （64.3%） and 31 cases （73.8%）, respectively. Both E-cadherin and P120 expressions were significantly correlated with the tumor histological grade （χ^2 = 9.333, P = 009 and χ^= 11.71, P = 0.003）, TNM stage （χ^= 8.627, P = 0.035 and χ^= 13.123, P = 0.004）, intrahepatic metastasis （χ^= 7.292, P = 0.007 and χ^= 4.657, P = 0.041, respectively） and patients′ survival （χ^= 6.351, P = 0.002 and χ^= 4.023, P = 0.000, respectively）. In addition, the expression of P120 was in concordance with that of E-cadherin （χ^ = 13.797, P = 0.000）, indicating that the expression of P120 may be dependent on that of E-cadherin. Finally, only P120 expression was found to be an independent prognostic factor in Cox regression model （r = 0.088, P = 0.049）. CONCLUSION： Down-regulated expression of E-cadherin and P120 occurs frequently in ICC and contributes to the progression and development of tumor. Both of them may be valuable biologic markers for predicting tumor invasion, metastasis and patients′ survival, but only P120 is an independent prognostic factor for ICC.

CLINICOPATHOLOGIC FEATURES AND DIAGNOSISOF COMBINED HEPATOCELLULAR ANDCHOLANGIOCARCINOMA

Hepatoma cases(N=130) were analyzed through histochemical and immunohistochemical staining. There were 99 cases of hepatocellular carcinoma(HCC), 15 cholangiocarcinoma(CC), and 16 combined HCC and CC (HCC+CC). The clinical features and the cases accompanied with hepatitis and/or liver cirrhosis in the non-tumor liver tissue of HCC+CC Group were between HCC GrouP and CC Group. Histologically, there were 4 cases with trabecular, 4 with pseudoglandula, 3 with solid type in HCCWC Group. In these 11 cases, the CC area was less than 10% of the neoplasm- The cases were classified as HCCWC type I. There was no obvious stroma fibrosis. The rest 5 cases of HCC+CC showed tubular carcinoma. The CC area took up over 10% of the tumor. These cases were designed as HCC+CC type II. There was significant fibrosis in the stroma so that its CC area is indistinguishable from that of CC cases. The CC area of all HCC+CC cases was positive to mucin and EMA staining, the same to that of CC cases. Near 70% of the HCC+CC cases had intracytoplasmic glycogen in the HCC area. The HCC area was mucin and EMA negative, similar to that of HCC cases- We also observed transition areas between HCC and CC in both of the type I and type II HCC+CC cases. The areas were mucin negative but EMA positive. We concluded that HCC+CC bad HCC and CC area. with the characteristics of HCC of CC respectively. Histochemical mucin staining and immunohistochemical EMA staining were valuable in detection and diagnosis of the HCC+CC.

Liver transplantation as an alternative for the treatment of perihilar cholangiocarcinoma: A critical review

Background:Perihilar cholangiocarcinoma(phCCC)is a dismal malignancy.There is no consensus regard-ing the best treatment for patients with unresectable phCCC.The present review aimed to gather the current pieces of evidence for liver transplantation and liver resection as a treatment for phCCC and to build better guidance for clinical practice.Data sources:The search was conducted in PubMed,Embase,Cochrane,and LILACS.The related references were searched manually.Inclusion criteria were:reports in English or Portuguese literature that a)patients with confirmed diagnosis of phCCC;b)patients treated with a curative intent;c)patients with the outcomes of liver resection and liver transplantation.Case reports,reviews,letters,editorials,conference abstracts and papers with full-text unavailability were excluded from the analysis.Results:Most of the current literature is based on observational retrospective studies with low grades of evidence.Liver resection has better long-term outcomes than systemic chemotherapy or palliation ther-apy and liver transplantation is a good alternative for selected patients with unresectable phCCC.All candidates for resection or transplantation should be medically fit and free of intrahepatic or extrahep-atic diseases.As a general rule,patients presenting with a tumor having a longitudinal size>3 cm or extending below the cystic duct,lymph node disease,confirmed extrahepatic dissemination;intraoper-atively diagnosed metastatic disease;a history of other malignancies within the last five years,and did not complete chemoradiation regimen and were medically unfit should not be considered for transplan-tation.Some of these criteria should be individually assessed.Liver transplantation or resection should only be considered in highly experienced hepatobiliary centers,and any decision-making must be based on a multidisciplinary evaluation.Conclusions:phCCC is a complex condition with high morbidity.Surgical therapies,including hepatec-tomy and liver transplantation,are the best option for better long-term disease-free survival.

Liver transplantation as an alternative for the treatment of intrahepatic cholangiocarcinoma: Past, present, and future directions

Intrahepatic cholangiocarcinoma(iCCA)is a rare biliary tract cancer with high mortality rate.Complete resection of the iCCA lesion is the first choice of treatment,with good prognosis after margin-negative resection.Unfortunately,only 12%-40% of patients are eligible for resection at presentation due to cirrhosis,portal hypertension,or large tumor size.Liver transplantation(LT)offers margin-negative iCCA extirpation for patients with unresectable tumors.Initially,iCCA was a contraindication for LT until size-based selection criteria were introduced to identify patients with satisfied post-LT outcomes.Recent studies have shown that tumor biology-based selection can yield high post-LT survival in patients with locally advanced iCCA.Another selection criterion is the tumor response to neoadjuvant therapy.Patients with response to neoadjuvant therapy have better outcomes after LT compared with those without tumor response to neoadjuvant therapy.Another index that helps predict the treatment outcome is the biomarker.Improved survival outcomes have also opened the door for living donor LT for iCCA.Patients undergoing LT for iCCA now have statistically similar survival rates as patients undergoing resection.The combination of surgery and locoregional and systemic therapies improves the prognosis of iCCA patients.

Current interventional options for palliative care for patients with advanced-stage cholangiocarcinoma

Primary biliary tract tumors are malignancies that originate in the liver,bile ducts,or gallbladder.These tumors often present with jaundice of unknown etiology,leading to delayed diagnosis and advanced disease.Currently,several palliative treatment options are available for primary biliary tract tumors.They include percutaneous transhepatic biliary drainage(PTBD),biliary stenting,and surgical interventions such as biliary diversion.Systemic therapy is also commonly used for the palliative treatment of primary biliary tract tumors.It involves the administration of chemotherapy drugs,such as gemcitabine and cisplatin,which have shown promising results in improving overall survival in patients with advanced biliary tract tumors.PTBD is another palliative treatment option for patients with unresectable or inoperable malignant biliary obstruction.Biliary stenting can also be used as a palliative treatment option to alleviate symptoms in patients with unresectable or inoperable malignant biliary obstruction.Surgical interventions,such as biliary diversion,have traditionally been used as palliative options for primary biliary tract tumors.However,biliary diversion only provides temporary relief and does not remove the tumor.Primary biliary tract tumors often present in advanced stages,making palliative treatment the primary option for improving the quality of life of patients.