Thinking and suggestion on the definition, classification and Chinese nomenclature of carcinoma of the bile ducts / 中华外科杂志

At present, the classification, nomenclature, and definition of carcinoma of the bile ducts are controversial. Moreover, there is no uniformity between China and aboard, which has brought confusion to clinical practice. It needs to clarify regarding tumor naming principles, anatomical location, tumor origin, pathological classification, biological characteristics, clinical manifestations, treatment methods, etc. Additionally, the WHO tumor classification, UICC staging, ICD disease classification, relevant Chinese regulations, EASL, AJCC staging, and NCCN guidelines were also needed to be referred. After investigating the above-mentioned latest authoritative literature, based on the existing problems, combined with clinical practice in China, the author reevaluated the definition, classification, and nomenclature of cholangiocarcinoma, and proposes updated suggestions. Hoping to standardize and unify clinical practice for classification and nomenclature of cholangiocarcinoma in China.

Colangiocarcinoma, diagnóstico, tratamiento y evolución clínica. Presentación de un caso con sobrevida 5 años / Cholangiocarcinoma: diagnosis, treatment and clinical evolution. Presentation of a case with five-year survival

RESUMEN El colangiocarcinoma es un tumor maligno originado en el epitelio de los conductos biliares intra o extrahepáticos. En el cuadro clínico destacan el dolor en hipocondrio derecho, ictericia y baja de peso. Actualmente, el diagnóstico se ha facilitado por la disponibilidad de variados procedimientos imagenológicos y endoscópicos. Se presentó un caso al que se le realizó el diagnóstico de este tipo de tumor. Se sometió a tratamiento endoscópico, quirúrgico y oncológico con Gemcitabina, Cisplatino y Oxaliplatino. Fue seguido por equipo multidisciplinario y evolucionó con sobrevida de 5 años (AU).

ABSTRACT Cholangiocarcinoma is a malignant tumor originated in the epithelium of the intra or extra hepatic biliary ducts. Pain in the right hypochondrium, jaundice and low weight are the main clinical features. Currently, the diagnosis has been facilitated by the availability of different imaging and endoscopic procedures. The authors presented a case diagnosed with this kind of tumor. The patient underwent surgical, endoscopic and oncologic treatment with gemcitabine, cisplatine and oxaliplatine. He was followed up by a multidisciplinary team and evolved with five-year survival (AU).

Expression of epidermal growth factor receptor (EGFR) in cholangiocarcinomas: predictive factors and survival / Expressão do receptor do fator de crescimento epitelial (EGFR) em colangiocarcinomas: fatores preditivos e sobrevida

ABSTRACT Objective: to evaluate the expression of the epithelial growth factor receptor (EGFR) by immunohistochemistry, and to verify its association with prognostic factors and survival of patients operated by cholangiocarcinoma. Methods: we verified the immunohistochemical expression of EGFR in 35 surgical specimens of cholangiocarcinoma (CCA). We obtained survival curves with the Kaplan-Meier method. Results: we found significant EGFR expression in ten (28.6%) of the 35 CCAs, eight with score 3 and two with score 2. Advanced stages (III and IV) presented higher EGFR expression (p=0.07). The clinical characteristics that were most associated with positive EGFR expression were female gender (p=0.06) and absence of comorbidities (p=0.06). Overall survival at 12, 24, 36 and 48 months was 100%, 82.5%, 59% and 44.2%, respectively. The survival of EGFR positive patients at 12, 24, 36 and 48 months was 100%, 75%, 50% and 0%, whereas for negative EGFR patients it was 100%, 87.5%, 65.6% and 65.6%, respectively. Conclusion: EGFR expression occurred in 28.6% of the cases studied and was associated with lower survival.

RESUMO Objetivo: avaliar a expressão do receptor do fator de crescimento epitelial (EGFR) por meio de imuno-histoquímica, e verificar sua associação com fatores prognósticos e com a sobrevida dos pacientes operados por colangiocarcinoma. Métodos: a expressão imuno-histoquímica de EGFR foi verificada em 35 peças cirúrgicas de colangiocarcinomas (CCA). Curvas de sobrevida foram obtidas pelo método de Kaplan-Meier. Resultados: expressão significativa de EGFR foi encontrada em dez (28,6%) de 35 CCA, oito com escore 3 e dois com escore 2. Estágios avançados (III e IV) apresentaram maior expressão de EGFR (p=0,07). As características clínicas que mais estiveram associadas com a expressão positiva de EGFR foram o sexo feminino (p=0,06) e ausência de comorbidades (p=0,06). A sobrevida global aos 12, 24, 36 e 48 meses foi de 100%, 82,5%, 59% e 44,2%, respectivamente. A sobrevida de pacientes EGFR positivos aos 12, 24, 36 e 48 meses foi de 100%, 75%, 50% e 0%, enquanto que para EGFR negativos foi de 100%, 87,5%, 65,6% e 65,6%, respectivamente. Conclusão: a expressão do EGFR ocorreu em 28,6% dos casos estudados e esteve associada a menor sobrevida.

Intrahepatic, Perihilar and Distal Cholangiocarcinoma: Management and Outcomes

Abstract: Introduction and aims. Cholangiocarcinomas are a heterogeneous group of tumors that can be classified into three clinically distinct types of cancers, intrahepatic, perihilar and distal cholangiocarcinoma. The inconsistent use of nomenclature for these cancers has obscured a true knowledge of the epidemiology, natural history and response to therapy of these cancers. Our aims were to define demographic characteristics, management and outcomes of these three distinct cancer types. Materials and methods. A retrospective study of patients enrolled in an institutional cancer registry from 1992 to 2010. Median survival was compared between different treatment modalities over three time periods for the three types of cholangiocarcinoma at different stages of the disease using Kaplan Meyer analysis. Results. 242 patients were identified. All cases were reviewed and classified into intrahepatic (90 patients), distal (48 patients) or perihilar (104 patients) cholangiocarcinomas. These cancers differed in median age of onset, gender distribution, median survival and stage. 13.8% of patients presented with stage I, 5.8% with stage II, 9.6% with stage III, 28% with stage IV, with 41.8% having unknown stage. The overall median survival was 15.8 months, and was 23, 25, 14, and 4.5 months for stages I, II, III, and IV respectively. Surgery improved survival in both early and advanced stages. Multimodality therapies further improved outcomes, particularly for perihilar cholangiocarcinoma. Conclusion. Perihilar, distal and intrahepatic cholangiocarcinoma vary in their presentation, natural history and therapeutic approach to management. A consistently applied classification is essential for meaningful interpretation of studies of these cancers.

Salinomycin enhances doxorubicin sensitivity through reversing the epithelial-mesenchymal transition of cholangiocarcinoma cells by regulating ARK5

Chemotherapy response rates in patients with cholangiocarcinoma remain low, primarily due to the development of drug resistance. Epithelial-mesenchymal transition (EMT) of cancer cells is widely accepted to be important for metastasis and progression, but it has also been linked to the development of chemoresistance. Salinomycin (an antibiotic) has shown some potential as a chemotherapeutic agent as it selectively kills cancer stem cells, and has been hypothesized to block the EMT process. In this study, we investigated whether salinomycin could reverse the chemoresistance of cholangiocarcinoma cells to the chemotherapy drug doxorubicin. We found that combined salinomycin with doxorubicin treatment resulted in a significant decrease in cell viability compared with doxorubicin or salinomycin treatment alone in two cholangiocarcinoma cell lines (RBE and Huh-28). The dosages of both drugs that were required to produce a cytotoxic effect decreased, indicating that these two drugs have a synergistic effect. In terms of mechanism, salinomycin reversed doxorubicin-induced EMT of cholangiocarcinoma cells, as shown morphologically and through the detection of EMT markers. Moreover, we showed that salinomycin treatment downregulated the AMP-activated protein kinase family member 5 (ARK5) expression, which regulates the EMT process of cholangiocarcinoma. Our results indicated that salinomycin reversed the EMT process in cholangiocarcinoma cells by inhibiting ARK5 expression and enhanced the chemosensitivity of cholangiocarcinoma cells to doxorubicin. Therefore, a combined treatment of salinomycin with doxorubicin could be used to enhance doxorubicin sensitivity in patients with cholangiocarcinoma.

Resultados del tratamiento quirúrgico del colangiocarcinoma intrahepático / Intrahepatic cholangiocarcinoma: experience in 30 operated patients

background: Intrahepatic cholangiocarcinoma (ICC) corresponds to 10% of liver primary malignant tumors. Aim: To show the results of surgical treatment of ICC in a biliary surgery center. material and methods: Review of a prospective database of operated patients at a surgical service of a clinical hospital. Thirty operated patients with an ICC, aged 25 to 83 years (20 women), were identified. Results: Twenty six patients had symptoms, 12 of 19 had high levels of CA19-9 and in four the tumor was non resectable. Twenty four patients underwent major hepatectomy and two, a minor hepatectomy. Combined resections were performed in three patients. Lymphadenectomy was performed in 14 patients and five had lymph node metastases. Surgical time was 272 minutes, mean intensive care unit stay was 10 days and mean ventilatory support use was five days. Surgical mortality was 19% and complications appeared in 53% of patients. Tumors were stage I, II, III and IV in 11, 5, 3 and 11 patients respectively. Overall survival was 16 months. Survival in tumors stage I and II was 50% at five years. In stages III and IV, it was 11.2 months. Conclusions: Surgery for ICC has an acceptable mortality and complications rate with a five years survival of 25%.

Introducción: El colangiocarcinoma intrahepático (CCIH), corresponde al segundo cáncer primario hepático, representando alrededor del 10% de los cánceres primarios del hígado; el tratamiento es la hepatectomía. Objetivo: Mostrar los resultados del tratamiento quirúrgico de pacientes con CCIH en Chile en un centro de cirugía hepatobiliar. Pacientes y métodos: Análisis prospectivo de los pacientes con CCIH operados en nuestro centro entre 2005 y 2015. Resultados: 30 pacientes, 20 mujeres (67%), 10 hombres (33%). Edad promedio: 60 años (rango 25-83 ), 26 pacientes sintomáticos (87%), CA19-9 elevado en 12 (63,2%), 4 pacientes (13%) irresecables, 24 pacientes (80%) hepatectomías mayores y 2 resecciones menores. Resecciones combinadas en 3, linfadenectomía en 14 pacientes (47%), metástasis linfonodales en 5 (17%). Tiempo promedio quirúrgico 272 min (rango 45-480). UCI, mediana 10 días, ventilación mecánica mediana 5 días. Hospitalización, mediana 10 días y 7 días postoperatorio. Morbilidad 53%, mortalidad 19%. R0 en 19 pacientes (64%), R1 en 7 pacientes (23%) y R2 en 4 pacientes (13%). Estadio I en 11 pacientes, estadio II en 5 pacientes, estadio III en 3 pacientes, estadio IV en 11 pacientes. Sobrevida general de 16 meses. Sobrevida estadio I 58,4 meses, estadio II 31,1 meses, estadio III 5,9 meses y estadio IV 11,8 meses, p = 0,06. Sobrevida R0 16 meses, R1: 31,1 meses y R2: 9,25 meses, p = 0,53. Sobrevida estadios I y II 50% a 5 años, estadios III-IV 11,2 meses, p < 0,01. Discusión: Este es el primer reporte nacional de una serie importante de pacientes con CCIH, con morbilidad y mortalidad aceptables. Sobrevida de 25% a 5 años.

Guideline for the management of bile duct cancers by the brazilian gastrointestinal tumor group

ABSTRACT The Brazilian Gastrointestinal Tumor Group developed guidelines for the surgical and clinical management of patients with billiary cancers. The multidisciplinary panel was composed of experts in the field of radiology, medical oncology, surgical oncology, radiotherapy, endoscopy and pathology. The panel utilized the most recent literature to develop a series of evidence-based recommendations on different treatment and diagnostic strategies for cholangiocarcinomas and gallbladder cancers.

RESUMO O Grupo Brasileiro de Tumores Gastrointestinais desenvolveu diretrizes de tratamento cirúrgico e clínico de pacientes com tumores de vias biliares. O painel multidisciplinar foi composto de especialistas nas áreas radiologia, oncologia, cirurgia, radioterapia, endoscopia e anatomia patológica. O painel utilizou literatura atual para desenvolver recomendações baseadas em evidência científica para as diferentes estratégias terapêuticas e diagnósticas dos colangiocarcinomas e tumores de vesícula biliar.

Histopathology of a benign bile duct lesion in the liver: Morphologic mimicker or precursor of intrahepatic cholangiocarcinoma

A bile duct lesion originating from intrahepatic bile ducts is generally regarded as an incidental pathologic finding in liver specimens. However, a recent study on the molecular classification of intrahepatic cholangiocarcinoma has focused on the heterogeneity of this carcinoma and has suggested that the cells of different origins present in the biliary tree may have a major role in the mechanism of oncogenesis. In this review, benign intrahepatic bile duct lesions—regarded in the past as reactive changes or remnant developmental anomalies and now noted to have potential for developing precursor lesions of intrahepatic cholangiocarcinoma—are discussed by focusing on the histopathologic features and its implications in clinical practice.

TGF-ß1 expression is associated with invasion and metastasis of intrahepatic cholangiocarcinoma

BACKGROUND: Transforming growth factor (TGF)-ß is involved in many physiologic processes, it often promotes metastasis, and its high expression is correlated with poor prognosis. In the present study, we analyzed the correlation between transforming growth factor beta 1 (TGF-ß1) expression and prognosis in intrahepatic cholangiocarcinoma RESULTS: We examined the expression of TGF-ß1 in 78 intrahepatic cholangiocarcinomas by immunohistochemistry and correlated the expression with clinicopathological parameters. TGF-ß1 was expressed in 37 of 78 (47.4 %) intrahepatic cholangiocarcinomas. The expression of TGF-ß1 was significantly correlated with lymph node metastasis, distant metastasis, and tumour recurrence. Patients with TGF-ß1-positive tumours had significantly shorter survival time. In a multivariant analysis, the expression of TGF-ß1 and the tumour stage were independent prognostic factors CONCLUSIONS: Our data suggest that expression of TGF-ß1 is a novel prognostic marker for intrahepatic cholangiocarcinoma.

Cancer Stem Cells in Primary Liver Cancers: Pathological Concepts and Imaging Findings

There is accumulating evidence that cancer stem cells (CSCs) play an integral role in the initiation of hepatocarcinogenesis and the maintaining of tumor growth. Liver CSCs derived from hepatic stem/progenitor cells have the potential to differentiate into either hepatocytes or cholangiocytes. Primary liver cancers originating from CSCs constitute a heterogeneous histopathologic spectrum, including hepatocellular carcinoma, combined hepatocellular-cholangiocarcinoma, and intrahepatic cholangiocarcinoma with various radiologic manifestations. In this article, we reviewed the recent concepts of CSCs in the development of primary liver cancers, focusing on their pathological and radiological findings. Awareness of the pathological concepts and imaging findings of primary liver cancers with features of CSCs is critical for accurate diagnosis, prediction of outcome, and appropriate treatment options for patients.

A case of hepatoblastoma misdiagnosed as combined hepatocellular carcinoma and cholangiocarcinoma in an adult

Hepatoblastoma usually occurs in children under the age of 2 years, with very few cases reported in adults. We experienced a case of adult hepatoblastoma in a 36-year-old female with chronic hepatitis B . She had experienced sudden onset abdominal pain. Her serum alpha-fetoprotein level was markedly elevated, and abdominal CT showed a 9-cm mass with internal hemorrhage in the right hepatic lobe with hemoperitoneum, so an emergency hepatic central bisectionectomy was performed. The initial histologic examination revealed that the mass mimicked combined hepatocellular carcinoma and cholangiocarcinoma with spindle-cell metaplasia of the cholangiocarcinoma element. Follow-up abdominal CT performed 3 months later showed a 5.5-cm metastatic mass in the left subphrenic area. Laparoscopic splenectomy with mass excision was performed, and hepatoblastoma was confirmed histologically. A histologic re-examination of previously obtained surgical specimens also confirmed the presence of hepatoblastoma. Metastatic hepatoblastoma was found at multiple sites of the abdomen during follow-up, and so chemotherapy with cisplatin, 5-fluorouracil (5-FU), and vincristine was applied, followed by carboplatin and doxorubicin . Despite surgery and postoperative chemotherapy, she died 12 months after symptom onset.

Sarcomatoid cholangiocarcinoma with osteoclast-like giant cells associated with hepatolithiasis: A case report

No abstract available.

Successful Xenograft of Endoscopic Ultrasound-Guided Fine-Needle Aspiration Specimen from Human Extrahepatic Cholangiocarcinoma into an Immunodeficient Mouse

Patient-derived tumor xenograft is the transfer of primary human tumors directly into an immunodeficient mouse. Patient-derived tumor xenograft plays an important role in the development and evaluation of new chemotherapeutic agents. We succeeded in generating a patient-derived tumor xenograft of a biliary tumor obtained by endoscopic ultrasound-guided fine-needle aspiration from a patient who had an inoperable extrahepatic cholangiocarcinoma. This patient-derived tumor xenograft will be a promising tool for individualized cancer therapy and can be used in developing new chemotherapeutic agents for the treatment of biliary cancer in the future.

Cholangiolocellular carcinoma with satellite nodules showing intermediate differentiation

No abstract available.

Hep Par-1: a novel immunohistochemical marker for differentiating hepatocellular carcinoma from metastatic carcinoma

To evaluate the diagnostic utility of Hep par-1 in differentiating hepatocellular carcinoma from metastatic carcinoma taking histopathology as a gold standard. Comparative cross-sectional study. Pathology Department, Shaukat Khanum Memorial Cancer Hospital and Research Centre, Lahore, from April 2007 to February 2008. Hep par-1 immunohistochemical stain was performed on 60 cases of liver carcinoma, 30 cases each of metastatic and hepatocellular carcinoma. Information regarding patient age, gender, sign and symptoms, radiographic findings, histological grade of tumour, and expression of Hep par-1 on hepatocellular and metastatic carcinoma were recorded on proforma sheet. Sensitivity, specificity, positive and negative predictive values, and accuracy of Hep par-1 were calculated using the formulas. Hep par-1 expression was noted in 25 out of 30 cases of hepatocellular carcinoma [83%]. Out of 30 cases of metastatic carcinoma, only one case expressed staining in < 5% tumour cells and remaining 29 cases showed no reactivity. The age of the patients with hepatocellular carcinoma ranged from 40 to 76 years with a median age of 60.5 years and 40 - 75 years for metastatic carcinomas with a median age of 57.5 years. Hep par-1 is a reliable immunohistochemical marker for cases of hepatocellular carcinoma [HCC]. It can be used along with other markers in morphologically difficult cases when differential diagnosis lies between poorly differentiated HCC and metastatic carcinoma of liver

Diffuse Metastasis to the Thyroid: Unique Ultrasonographic Finding and Clinical Correlation

Cases of metastases to the thyroid gland seem to be increasing in recent years. The clinical and ultrasonographic findings of diffuse metastases have been sparsely reported. Thirteen cases of diffuse metastases to the thyroid gland were documented by thyroid ultrasonography-guided fine needle aspiration cytology between 2004 and 2013. We retrospectively reviewed the patients with diffuse thyroid metastases. The most common primary site was the lung (n=9), followed by unknown origin cancers (n=2), cholangiocarcinoma (n=1), and penile cancer (n=1). Eleven patients were incidentally found to have thyroid metastases via surveillance or staging FDG-PET. Other 2 patients were diagnosed during work-up for hypothyroidism and palpable cervical lymph nodes. On ultrasonography, the echogenicity of the enlarged thyroid gland was heterogeneously hypoechoic or isoechoic, and reticular pattern internal hypoechoic lines were observed without increased vascularity found by power Doppler ultrasonography (3 right lobe, 2 left lobe, and 8 both lobes). In the 8 patients who had involvement of both lobes, 3 had hypothyroidism. In conclusion, ultrasonographic finding of diffuse metastasis is a diffusely enlarged heterogeneous thyroid with reticular pattern internal hypoechoic lines. Thyroid function testing should be performed in all patients with diffuse thyroid metastases, especially those with bilateral lobe involvement.

Diagnostic Accuracy of Brush Cytology with Direct Smear and Cell-block Techniques according to Preparation Order and Tumor Characteristics in Biliary Strictures / 대한소화기학회지

BACKGROUND/AIMS: There are few data supporting the diagnostic yield of brush cytology depending on the order of cytologic preparation method or the location or shape of tumors in biliary strictures. We investigated diagnostic yields and variations in brush cytology with direct smear and cell-block preparations according to sampling preparation sequence and tumor location and shape in biliary strictures. METHODS: Patients who had undergone ERCP with tissue sampling between August 2009 and April 2013 were analyzed retrospectively. Group A was examined using brush cytology with direct smear followed by cell-block with or without biopsy, while the reverse order was performed for group B. RESULTS: Among 138 enrolled patients, 92 patients (A: 36, B: 56) underwent both brush cytology with direct smear and cell-block preparations. No differences in sensitivity, specificity, or accuracy were observed according to the sampling preparation method and the location or shape of tumors in biliary strictures. The cellularity observed from brush cytology with direct smear was better than that from cell-block according to the location of the tumor (p<0.01). The diagnostic yield was increased in both groups with addition of an endobiliary biopsy. CONCLUSIONS: No difference in diagnostic accuracy was observed between the sequences of preparation for brush cytology with direct smear and cell-block techniques. Brush cytology showed better cellularity for diagnosis.

Intrahepatic cholangiocarcinoma arising in Caroli's disease

No abstract available.

Can combination metronomic therapy overcome chemoresistance in cholangiocarcinoma: A literature review.

Cholangiocarcinoma (CCa) is relatively resistant to chemotherapy as well as radiation therapy, and complete resection is the main curative therapy for these patients. The prognosis for patients with unresectable intrahepatic CCa (iCCa) is extremely poor. A 55‑year‑old woman presented at our hospital with abdominal pain. After evaluation, she was diagnosed to have multifocal iCCa. She did not opt for standard chemotherapy and therefore received oral metronomic therapy with a combination of celecoxib, etoposide, and cyclophosphamide for a total of 30 months. Presently, she is 57 months post diagnosis and 27 months post cessation of all treatment and continues to be in complete radiological remission. In the present report, we review the literature and discuss whether metronomic scheduling of biologic agents and anticancer drugs will be able to overcome chemoresistance and improve the outcome in cholangiocarcinoma. References for the review were identified through searches of Pubmed for the last 10 years as well as searches of the files of the authors themselves. The final list was generated on the basis of originality and relevance to this review.

Modified Retroperitoneal Access for Percutaneous Intervention after Pancreaticoduodenectomy

Percutaneous access to the surgical bed after pancreaticoduodenectomy can be a challenge, due to the post-operative anatomy alteration. However, immediate complications, such as surgical bed abscess or suspected tumor recurrence, are often best accessed percutaneously, as open surgical or endoscopic approaches are often difficult, if not impossible. We, hereby, describe a safe approach that is highly replicable, in accessing the surgical bed for percutaneous intervention, following pancreaticoduodenectomy.