Current status and future perspectives on the methods of prognosis evaluation for intrahepatic cholangiocarcinoma / 中华外科杂志

Intrahepatic cholangiocarcinoma (ICC) is the second most common primary malignant tumor in the liver after hepatocellular carcinoma. Its incidence and mortality rates have increased worldwide in recent years. Surgical resection is the best treatment modality for ICC;however,the overall prognosis remains poor. Accurate evaluation of post operative prognosis allows personalized treatment and improved long-term outcomes of ICC. The American Joint Commission on Cancer TNM staging manual is the basis for the standardized diagnosis and treatment of ICC;however,the contents of stage T and stage N need to be improved. The nomogram model or scoring system established in the analysis of commonly used clinicopathological parameters can provide individualized prognostic evaluation and improve prediction accuracy;however,more studies are needed to validate the results before clinical use. Meanwhile,imaging features exhibit great potential to establish the post operative prognosis evaluation system for ICC. Molecular-based classification provides an accurate guarantee for prognostic assessment as well as selection of populations that are sensitive to targeted therapy or immunotherapy. Therefore,the establishment of a prognosis evaluation system,based on clinical and pathological characteristics and centered on the combination of multidisciplinary and multi-omics,will be conducive to improving the long-term outcomes of ICC after surgical resection in the context of big medical data.

Excerpt from the 2022 American Association for the Study of Liver Diseases clinical practice guideline: management of primary sclerosing cholangitis and cholangiocarcinoma / 中华肝脏病杂志

What are the new contents of the guideline since 2010?A.Patients with primary and non-primary sclerosing cholangitis (PSC) are included in these guidelines for the diagnosis and management of cholangiocarcinoma.B.Define "related stricture" as any biliary or hepatic duct stricture accompanied by the signs or symptoms of obstructive cholestasis and/or bacterial cholangitis.C.Patients who have had an inconclusive report from MRI and cholangiopancreatography should be reexamined by high-quality MRI/cholangiopancreatography for diagnostic purposes. Endoscopic retrograde cholangiopancreatography should be avoided for the diagnosis of PSC.D. Patients with PSC and unknown inflammatory bowel disease (IBD) should undergo diagnostic colonoscopic histological sampling, with follow-up examination every five years until IBD is detected.E. PSC patients with IBD should begin colon cancer monitoring at 15 years of age.F. Individual incidence rates should be interpreted with caution when using the new clinical risk tool for PSC for risk stratification.G. All patients with PSC should be considered for clinical trials; however, if ursodeoxycholic acid (13-23 mg/kg/day) is well tolerated and after 12 months of treatment, alkaline phosphatase (γ- Glutamyltransferase in children) and/or symptoms are significantly improved, it can be considered to continue to be used.H. Endoscopic retrograde cholangiopancreatography with cholangiocytology brushing and fluorescence in situ hybridization analysis should be performed on all patients suspected of having hilar or distal cholangiocarcinoma.I.Patients with PSC and recurrent cholangitis are now included in the new unified network organ sharing policy for the end-stage liver disease model standard.J. Liver transplantation is recommended after neoadjuvant therapy for patients with unresectable hilar cholangiocarcinoma with diameter < 3 cm or combined with PSC and no intrahepatic (extrahepatic) metastases.

Urgent liver retransplantation due to transmission of intrahepatic cholangiocarcinoma by donor: the first report in the literature / Retransplante de fígado urgente devido à transmissão de colangiocarcinoma intra-hepático pelo doador: o primeiro relato da literatura

ABSTRACT BACKGROUND: Liver transplantation represents the best therapeutic modality in end-stage chronic liver disease, severe acute hepatitis, and selected cases of liver tumors. AIMS: To describe a double retransplant in a male patient diagnosed with Crohn's disease and complicated with primary sclerosing cholangitis, severe portal hypertension, and cholangiocarcinoma diagnosed in the transplanted liver. METHODS: A 48-year-old male patient diagnosed with Crohn's disease 25 years ago, complicated with primary sclerosing cholangitis and severe portal hypertension. He underwent a liver transplantation in 2018 due to secondary biliary cirrhosis. In 2021, a primary sclerosing cholangitis recurrence was diagnosed and a liver retransplantation was indicated. Recipient's hepatectomy was very difficult by reason of complex portal vein thrombosis requiring extensive thromboendovenectomy. Intraoperative ultrasound with liver doppler evaluation was performed. Two suspicious nodules were incidentally diagnosed in the donor's liver and immediately removed for anatomopathological evaluation. RESULTS: After pathological confirmation of carcinoma, probable cholangiocarcinoma, at frozen section, the patient was re-listed as national priority and a new liver transplantation was performed within 24 hours. The patient was discharged after 2 weeks. CONCLUSIONS: The screening for neoplasms in donated organs should be part of our strict daily diagnostic arsenal. Moreover, we argue that, for the benefit of an adequate diagnosis and the feasibility of a safer procedure, the adoption of imaging tests routine for the liver donor is essential, allowing a reduction of the costs and some potential risks of liver transplant procedure.

RESUMO RACIONAL: O transplante de fígado representa a melhor modalidade terapêutica na doença hepática crônica terminal, hepatite aguda grave e casos selecionados de tumores hepáticos. OBJETIVOS: Descrever um retransplante duplo em paciente do sexo masculino, diagnosticado com doença de Crohn e complicado com colangite esclerosante primária, hipertensão portal grave e colangiocarcinoma diagnosticado no fígado transplantado. MÉTODOS: Paciente do sexo masculino, 48 anos, diagnosticado com doença de Crohn há 25 anos e complicado com colangite esclerosante primária e hipertensão portal grave. Foi submetido a um transplante de fígado em 2018 devido a cirrose biliar secundária. Em 2021, foi diagnosticada recidiva de colangite esclerosante primária e indicado retransplante hepático. A hepatectomia do receptor foi de alta complexidade devido à trombose complexa da veia porta, exigindo extensa tromboendovenectomia. Foi realizada ultrassonografia intraoperatória com doppler hepático. Dois nódulos suspeitos foram diagnosticados incidentalmente no fígado do doador e imediatamente removidos para avaliação anatomopatológica. RESULTADOS: Após confirmação patológica de carcinoma, provável colangiocarcinoma, pela congelação, o paciente foi relistado como prioridade nacional, e novo transplante hepático foi realizado em 24 horas. O paciente teve alta após 2 semanas. CONCLUSÕES: O rastreamento de neoplasias em órgãos doados deve fazer parte de nosso estrito arsenal diagnóstico diário. Além disso, defendemos que, em benefício de um diagnóstico correto e da viabilidade de um procedimento mais seguro, a adoção de uma rotina de exames de imagem é essencial em doadores hepáticos, permitindo a redução dos custos e alguns riscos potenciais do procedimento de transplante hepático.

Colangiocarcinoma y hepatocolangiocarcinoma combinado en pacientes con cirrosis / Cholangiocarcinoma and combined hepatocellular-cholangiocarcinoma in cirrhotic patients

Background: Cholangiocarcinoma (CCA) is a primary hepatic tumor, frequently found in patients with liver cirrhosis and biliary tract diseases. Its varieties include isolated CCA or "combined hepatocellular-cholangiocarcinoma" (cHCC-CCA). The latter is uncommon, with poorly defined diagnostic criteria and natural history. Aim: To characterize patients with cirrhosis with a pathological diagnosis of CCA and cHCC-CCA. Material and Methods: Forty-nine liver biopsies with a pathological diagnosis of CCA were reviewed. The clinical records of patients were reviewed to fetch demographic variables, etiology of cirrhosis and clinical presentation. Results: Eight of the 49 patients had cirrhosis (16% of CCA biopsies reviewed). Their median age was 64 (27-71) years and five were females. Four patients had CCA, three patients cHCC-CCA and one had a bifocal tumor. Patients in the CCA group were more commonly symptomatic. Alpha-fetoprotein and CA 19-9 levels were elevated in one of eight and four of six patients, respectively. Within 12 months from diagnosis, five of eight patients died. Conclusions: In most of these cases, the diagnosis of cHCC-CCA and CCA was made in the liver explant study without previous imaging diagnosis. This reinforces the usefulness of the histological study, in specific cases, prior to liver transplantation and emphasizes the importance of systematic explant exploration in these cases.

Neoplasia papilar intraductal de la vía biliar / Intraductal papillary neoplasm of the bile duct / Neoplasia papilar intraductal da via biliar

La neoplasia papilar intraductal de la vía biliar (NPIVB) es una entidad infrecuente caracterizada por el crecimiento exofítico papilar del epitelio biliar hacia la luz ductal. Previamente incluida en el grupo de tumores del mismo nombre de localización pancreática, presenta diferencias evidentes con ellos y desde 2010 se considera una entidad propia con demostrado potencial de malignización hacia colangiocarcinoma.

Papillary intraductal neoplasia of the bile duct (NPIVB) is a rare entity characterized by exophytic papillary growth of the biliary epithelium towards the ductal lumen. Previously included in the group of tumors of the same name in pancreatic location, it presents obvious differences with them and since 2010 it has been considered a separate entity with demonstrated potential for malignancy towards cholangiocarcinoma.

O neoplasma papilar intraductal da via biliar (NPIVB) é uma entidade infrequente por el creciento exofítico papilar do epitélio biliar hacia la luz ductal. Obviamente incluído no grupo de tumores do mismo nombre de localização pancreática, apresenta diferenças evidentes com ellos e desde 2010 se considerar uma entidade propia com potencial demonstrado de malignización hacia cholangiocarcinoma.

Nuevos avances en cirugía hepática: evaluación y planificación preoperatoria (Parte 1) / New advances in liver surgery: evaluation and preoperative planning

Resumen Los avances en la cirugía hepática de los últimos años han permitido resecciones hepáticas más extensa y complejas para el tratamiento de diferentes patologías del hígado sin un aumento excesivo de la morbimortalidad perioperatoria. El desarrollo de diferentes técnicas, tecnologías y herramientas para la evaluación preoperatoria han mejorado la planificación quirúrgica con el uso por ejemplo de las tecnologías audiovisuales e impresión de modelos en 3 dimensiones (3D) de alta fidelidad. Otros avances, han permitido realizar una mejor evaluación funcional del parénquima hepático y una caracterización más precisa de las lesiones con el uso por ejemplo de verde de indocianina, cintigrafía hepática y resonancia magnética con contraste hepatoespecífico. Este artículo describe algunos de los nuevos avances en la evaluación y planificación preoperatoria en cirugía hepática.

Advances in liver surgery in recent years have made it possible to achieve more extensive and complex liver resections for the treatment of different liver diseases without an excessive increase in perioperative morbidity and mortality. The development of different techniques, technologies and tools for preoperative evaluation have improved surgical planning with the use, for example, of audiovisual technologies and printing of high-fidelity 3-dimensional (3D) models. Other advances have allowed a better functional evaluation of the liver parenchyma and a more precise characterization of the lesions with the use, for example of indocyanine green or liver scintigraphy and magnetic resonance with hepatospecific contrast. This article describes some of the new advances in preoperative evaluation and planning in liver surgery.

The effect of prealbumin on the long-term prognosis of hilar cholangiocarcinoma following radical surgery / 中华外科杂志

Objective: To investigate the association between prealbumin and the long-term prognosis of patients with hilar cholangiocarcinoma(HCCA) following radical surgery. Methods: The clinical data of 262 HCCA patients who underwent radical surgery admitted from January 2010 to January 2017 at the First Affiliated Hospital of Army Medical University were collected,retrospectively. There were 158 males and 104 females; aged (57.6±9.9)years old(range:32 to 78 years). According to the preoperative serum prealbumin level(170 mg/L),the patients were divided into low prealbumin group(n=143) and normal prealbumin group(n=119). Follow-up until September 2020,the main research indicator was overall survival(OS), and the secondary research indicator was recurrence-free survival(RFS). The measurement data conforming to the normal distribution adopted the t test,the measurement data not conforming to the normal distribution adopted the Mann-Whitney U test,and the count data adopted the χ2 test. The Kaplan-Meier method was used to calculate the cumulative survival rate. The Log-rank test was used for univariate analysis of the cumulative survival rate. Variables with P<0.10 in univariate analysis were included in the Cox proportional hazards model for multivariate analysis. Results: The 1-, 3-, and 5-year OS rate of the 262 patients was 73.4%, 32.1%, and 24.0%, respectively, and the 1-, 3-, and 5-year RFS rate was 54.6%, 25.2%, and 16.2%, respectively. Median OS and RFS were 21 months and 12 months for patients with low prealbumin and 25 months and 19 months for patients with normal prealbumin. The OS rate and RFS rate of patients in the low prealbumin group were lower than those in the normal prealbumin group, and the difference was statistically significant (both P<0.05). The results of univariate analysis indicated that low prealbumin, CA19-9>150 U/L, tumor infiltration length>3 cm, preoperative jaundice, macrovascular invasion, microvascular invasion, lymph node metastasis, and poor differentiation maybe the risk factors of OS,and low prealbumin,tumor invasion length>3 cm,macrovascular invasion, microvascular invasion,lymph node metastasis,and poor differentiation maybe the risk factors of RFS for postoperative for radical resection in patients with HCCA (all P<0.10). Multivariate results suggested that low prealbumin,tumor invasion length>3 cm,microvascular invasion,lymph node metastasis,and poor differentiation were independent risk factors affecting OS and RFS in patients with HCCA after radical operation (all P<0.05). Conclusion: Preoperative prealbumin level can predict the long-term prognosis of patients with hilar cholangiocarcinoma following radical surgery.

A novel nomogram for individualized preoperative prediction of lymph node metastasis in patients with intrahepatic cholangiocarcinoma / 中华外科杂志

Objective: Constructing and validating a nomogram model for preoperative prediction of intrahepatic cholangiocarcinoma (ICC) lymph node metastasis to assist decision making during surgery. Methods: Retrospectively collecting the clinical and pathological data of 1 031 ICC patients who underwent partial hepatectomy at Eastern Hepatobiliary Surgery Hospital of Naval Military Medical University,General Hospital of Eastern Theater Command,or Zhongda Hospital Southeast University from January 2003 to January 2014. There were 682 males and 349 females; mean age was 54.7 years(range:18 to 82 years). There were 562 patients who underwent lymph node dissection and 469 patients who did not. Among the patients in the dissection group,Lasso regression method was used to filtrate preoperative variables related to lymph node metastasis and establish a nomogram. Bootstrap method was used to internally validate the discrimination of the nomogram,and the accuracy of the nomogram was assessed by using calibration curves. Patients were divided into low-moderate and high-risk groups based on model prediction probability. Propensity score matching(PSM) was used to analyze the overall survival (OS) and recurrence-free survival (RFS) of patients with and without lymph node dissection in the two groups,and to judge the importance of lymph node dissection in the two groups. Results: Six factors related to ICC lymph node metastasis were determined by Lasso regression,including hepatitis B surface antigen,CA19-9,age,lymphadenopathy,carcinoembryo antigen and maximum tumor diameter. These factors were integrated into a nomogram to predict ICC lymph node metastasis. The aera under curve value was 0.764,and the C-index was 0.754. Stratified analysis showed that OS and RFS in the high-risk group of lymph node metastasis were significantly lower than those in the low-medium risk group(median OS:14.6 months vs. 27.0 months,P<0.01; median RFS:9.1 months vs. 15.5 months,P<0.01). In the high-risk group,the median OS was 16.7 months and 6.3 months(Log-rank test: P=0.187;Wilcoxon test:P=0.046),and the median RFS was 11.0 months and 4.8 months(P=0.403),respectively in the lymph node dissection group and undissected group after PSM. In the low-medium-risk group,the median OS was 22.7 months and 26.7 months(P=0.288),and the median RFS was 13.0 months and 14.5 months(P=0.306),respectively in the lymph node dissection group and undissected group after PSM. Conclusions: The nomogram could be used for preoperative prediction of lymph node metastasis and prognostic stratification in patients with ICC. For patients with high risk of lymph node metastasis predicted by the model,active dissection should be performed. For patients predicted to be at low-moderate risk,lymph node dissection might be optional in some specific cases.

Impact of adjuvant chemotherapy on prognosis in intrahepatic cholangiocarcinoma patients underwent radical resection / 中华外科杂志

Objectives: To investigate the clinical value of adjuvant chemotherapy(ACT) in patients with intrahepatic cholangiocarcinoma(ICC) who underwent radical resection and to explore the optimal population that can benefit from ACT. Methods: A retrospective cohort study method was adopted. The clinical and pathological data of 685 patients with ICC who underwent curative intent resection in 10 Chinese hepatobiliary surgery centers from January 2010 to December 2018 were collected;There were 355 males and 330 females. The age(M(IQR)) was 58(14) years (range: 22 to 83 years). Propensity score matching(PSM) was applied to balance the differences between the adjuvant and non-adjuvant chemotherapy groups. Log-rank test was used to compare the prognosis of the two groups of patients. A Bayesian network recurrence-free survival(RFS) prediction model was constructed using the median RFS time (14 months) as the target variable, and the importance of the relevant prognostic factors was ranked according to the multistate Birnbaum importance calculation. A survival prognostic prediction table was established to analyze the population benefiting from adjuvant chemotherapy. Results: Among 685 patients,214 received ACT and 471 did not receive ACT. A total of 124 pairs of patients were included after PSM, and patients in the ACT group had better overall survival (OS) and RFS than those in the non-ACT group(OS: 32.2 months vs. 18.0 months,P=0.003;RFS:18.0 months vs. 10.0 months,P=0.001). The area under the curve of the Bayesian network RFS prediction model was 0.7124. The results of the prognostic factors in order of importance were microvascular invasion (0.158 2),perineural invasion (0.158 2),N stage (0.155 8),T stage (0.120 9), hepatic envelope invasion (0.090 3),adjuvant chemotherapy (0.072 1), tumor location (0.057 5), age (0.042 3), pathological differentiation (0.034 0), sex (0.029 3), alpha-fetoprotein (0.028 9) and preoperative jaundice (0.008 5). A survival prediction table based on the variables with importance greater than 0.1 (microvascular invasion,perineural invasion,N stage,T staging) and ACT showed that all patients benefited from ACT (increase in the probability of RFS≥14 months from 2.21% to 7.68%), with a more significant increase in the probability of RFS≥14 months after ACT in early-stage patients. Conclusion: ACT after radical resection in patients with ICC significantly prolongs the OS and RFS of patients, and the benefit of ACT is greater in early patients.

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.

Value of albumin RNAscope in situ hybridization in diagnosis and differential diagnosis of hepatocellular carcinoma / 中华病理学杂志

Objective: To investigate the utility of albumin RNAscope in situ hybridization in the diagnosis and differential diagnosis of hepatocellular carcinoma and its mimics. Methods: One hundred and fifty-two cases of hepatocellular carcinoma and its mimics and 33 cases of normal tissue were selected from the pathology database of the Department of Pathology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine from January 2013 to December 2019. Tissue microarrays were constructed and RNAscope in situ hybridization was performed to detect the expression of albumin mRNA. Results: No albumin mRNA expression was detected in normal tissues except for the liver. All hepatocellular carcinoma regardless of its degree of differentiation and primary or metastatic nature had detectable albumin mRNA, with strong and diffuse staining in 90.7% (49/54) of cases. While the positive rate of HepPar-1, Arg-1 or one of them by immunohistochemistry was 87.0% (47/54), 85.2% (46/54) and 92.6% (50/54) respectively. The positive rates of albumin mRNA in intrahepatic cholangiocarcinoma and biphenotypic hepatocellular carcinoma were 7/15 and 9/10, respectively. The former showed focal or heterogeneous staining, while the latter showed strong and diffuse staining. The positive rate of hepatoid adenocarcinoma was 8/19, and the albumin expression could be diffuse or focal. Sporadic cases of poorly differentiated gastric adenocarcinoma and metastatic colon adenocarcinoma showed focal staining of albumin mRNA. Conclusions: Detection of albumin mRNA by RNAscope in situ hybridization is of great value for the diagnosis and differential diagnosis of HCC, and the sensitivity may be improved by combining with HepPar-1 and Arg-1. It also offers different diagnostic clues according to different expression patterns.

Differential Expression of Long Non-coding RNA Cancer Susceptibility Candidate 2 and Imprinted Gene H19 in Extrahepatic Cholangiocarcinoma / 中国医学科学院学报

Objective To investigate the expression and the potential roles of long non-coding RNA(lncRNA)cancer susceptibility candidate 2(CASC2)and imprinted gene H19 in extrahepatic cholangiocarcinoma(ECC). Methods Four samples from patients with ECC were collected for high-throughput sequencing which was conducted to reveal the transcriptomic profiles of lncRNA CASC2 and H19.Bioinformatics tools were employed to predict the potential roles of the two genes.Another 22 ECC tissue samples and the cholangiocarcinoma cell lines(RBE,QBC939,HuH-28,and HuCCT1)with different degrees of differentiation were selected for validation.The para-carcinoma tissue and normal human intrahepatic biliary epithelial cell(HIBEC)were used as the control groups.The expression levels of lncRNA CASC2 and H19 in carcinoma tissue,para-carcinoma tissue,and cell lines were determined by real-time quantitative polymerase chain reaction(qRT-PCR).The correlation analysis was carried out for the clinical indicators of patients with the expression levels of the target genes. Results The two target genes showed significantly different expression between carcinoma tissue and para-carcinoma tissue(all P<0.05).Specifically,CASC2 had higher expression level in the carcinoma tissue than in the para-carcinoma tissue(t=1.262,P=0.025),whereas the expression of H19 showed an opposite trend(t=1.285,P=0.005).The expression levels of CASC2 in QBC939(t=8.114,P=0.015)and HuH-28(t=9.202,P=0.012)cells were significantly higher than that in the control group.The expression levels of H19 were significantly lower in RBE(t=-10.244,P<0.001),QBC939(t=-10.476,P<0.001),HuH-28(t=-19.798,P<0.001),and HuCCT1(t=-16.193,P=0.004)cells than in the control group.Bioinformatics analysis showed that CASC2 was mainly involved in the metabolic process and H19 in the development of multicellular organisms.Both CASC2 and H19 were related to catalytic activity.The expression level of lncRNA CASC2 was correlated with pathological differentiation(χ 2=6.222,P=0.022)and lymph node metastasis(χ2=5.455,P=0.020),and that of lncRNA H19 with pathological differentiation(χ2=1.174,P=0.029)and tumor size(χ2=-0.507,P=0.037). Conclusions In the case of ECC,lncRNA CASC2 and H19 have transcription disorders.lncRNA CASC2 is generally up-regulated in the carcinoma tissue,while H19 is down-regulated.Both genes have the potential to become new molecular markers for ECC.

Aneurisma de la aorta abdominal asociado a íctero / Aneurysm of the abdominal aorta associated with icterus

El aneurisma de la aorta abdominal como causa de íctero obstructivo es una situación de excepción en la clínica. El objetivo de esta presentación fue exponer la coexistencia del aneurisma de la aorta abdominal y el íctero. Una asociación muy poco frecuente y de difícil diagnóstico, que coloca al cirujano vascular en la toma de una especial conducta terapéutica. La cuidadosa revisión de los antecedentes patológicos y el análisis del comportamiento clínico del paciente permitieron la solución terapéutica adecuada. Se logró demostrar que el íctero obedecía a una lesión maligna de vías biliares conocida como colangiocarcinoma, que concomitó con la existencia de un aneurisma del V segmento aórtico y no fue el resultado de una compresión extrínseca de la dilatación de la aorta, sobre las vías biliares. La conducta quirúrgica, encaminada a erradicar el íctero y evitar la ruptura aneurismática con resección del aneurisma y colocación de prótesis, no resultó posible por lo avanzado de la lesión tumoral y el grado de metástasis ya establecidos. Solo se realizó resección de la vesícula biliar y seguimiento posterior por oncología(AU)

Abdominal aortic aneurysm as a cause of obstructive icterus is an exceptional situation in the clinic. The aim of this presentation was to expose the coexistence of abdominal aortic aneurysm and icterus. A very rare and difficult to diagnose association, which places the vascular surgeon in a special therapeutic approach. The careful review of the pathological history and the analysis of the patient's clinical behavior allowed the appropriate therapeutic solution. It was possible to demonstrate that the icterus was due to a malignant lesion of the biliary tract known as cholangiocarcinoma, which concomitated with the existence of an aneurysm of the V aortic segment and was not the result of extrinsic compression of the dilatation of the aorta on the biliary tract. The surgical procedure, aimed at eradicating the icterus and avoiding aneurysmal rupture with aneurysm resection and prosthesis placement, was not possible due to the advanced tumor lesion and the degree of metastasis already established. Only gallbladder resection was performed and subsequent follow-up by oncology(AU)

Protocol for liver transplantation in hilar cholangiocarcinoma / Protocolo de transplante hepático para colangiocarcinoma hilar

ABSTRACT Background: Hilar cholangiocarcinoma represents more than half of all cholangiocarcinoma cases, having poor prognosis and presenting a median overall survival after diagnosis of 12-24 months. In patients who have unresectable tumors with a better prognosis, the proposal to perform liver transplantation emerged for expanding the possibility of free margins by performing total hepatectomy. Aim: To provide a Brazilian protocol for liver transplantation in patients with hilar cholangiocarcinoma. Method: The protocol was carried out by two Brazilian institutions which perform a large volume of resections and liver transplantations, based on the study carried out at the Mayo Clinic. The elaboration of the protocol was conducted in four stages. Result: A protocol proposal for this disease is presented, which needs to be validated for clinical use. Conclusion: The development of a liver transplantation protocol for cholangiocarcinoma aims not only to standardize the treatment, but also enable a better assessment of the surgical results in the future.

RESUMO Racional: O colangiocarcinoma hilar representa mais da metade de todos os casos de colangiocarcinoma; tem prognóstico reservado e sobrevida global mediana de 12- 24 meses após o diagnóstico. A proposta de realizar transplante hepático surgiu para ampliar a possibilidade de margens livres através de hepatectomia total nos portadores de tumoresirressecáveis com melhor prognóstico. Objetivo: Apresentar protocolo brasileiro para realização de transplante hepático em pacientes com colangiocarcinoma hilar. Método: O protocolo foi realizado por duas instituições com grande volume de ressecções e transplantes hepáticos no Brasil, baseado no trabalho realizado pela MayoClinic. A elaboração foi dividida em quatro etapas. Resultado: É apresentada proposta de protocolo para esta doença a ser validada na aplicação clínica. Conclusão: Foi possível elaborar protocolo de transplante hepático para colangiocarcinoma a fim de uniformizar o tratamento e melhor avaliar os resultados cirúrgicos.

Elementos etiopatogénicos y diagnósticos del tumor de Klatskin o colangiocarcinoma hiliar / Etiopathogenetic and Diagnostic Elements of Klatskin's Tumor or Hilar Cholangiocarcinoma

RESUMEN Introducción: El colangiocarcinoma hiliar es un tumor poco frecuente, de mal pronóstico y elevada mortalidad; con un curso silente hasta la fase avanzada de la enfermedad. Objetivo: Describir la etiopatogenia y el diagnóstico por imágenes del colangiocarcinoma hiliar. Métodos: De las bases datos PubMed, SciELO y Latindex, se seleccionaron artículos publicados desde 2005 hasta mayo de 2020, relacionados con el colangiocarcinoma hiliar/ perihiliar: etiopatogenia, diagnóstico clínico, estudios de laboratorio y estudios imaginológicos. Desarrollo: Ictericia obstructiva (90 por ciento), pérdida de peso (60 - 75 por ciento) y dolor abdominal (40 por ciento) constituyen los síntomas de presentación más frecuentes. Los factores predisponentes, genéticos y ambientales, desencadenan respuesta inflamatoria crónica que lesionan el DNA de las células ductales provocando diferenciación celular anómala con el desarrollo de colangiocarcinoma. Las infecciones parasitarias y enfermedad litiásica de las vías biliares, en países orientales y la colangitis esclerosante primaria, en occidente, constituyen los principales factores predisponentes. El trípode para el diagnóstico lo conforman: la ecografía, tomografía axial computarizada y la resonancia magnética nuclear. Conclusiones: El colangiocarcinoma hiliar es una causa de colestasis poco frecuente en la población general, con un predominio sexta década de la vida y en el sexo masculino, siendo la ictericia el motivo de consulta de estos pacientes, donde la ecografía y la tomografía axial computarizada juegan el papel más importante en su diagnóstico y donde la clasificación de Bismuth-Corlette y TNM son esenciales para la correcta planificación del tratamiento(AU)

ABSTRACT Introduction: Hilar cholangiocarcinoma is a rare tumor, with poor prognosis and high mortality, with a silent course until the advanced stage of the disease. Objective: To describe the etiopathogenesis and imaging diagnosis of hilar cholangiocarcinoma. Methods: From the PubMed, SciELO and Latindex databases, articles published from 2005 to May 2020 were selected, insofar they were related to hilar/perihilar cholangiocarcinoma: etiopathogenesis, clinical diagnosis, laboratory studies and imaging studies. Development: Obstructive jaundice (90 percent), weight loss (60-75 percent) and abdominal pain (40 percent) are the most frequent presenting symptoms. Predisposing factors, either genetic and environmental, trigger chronic inflammatory responses that damage the DNA of ductal cells, causing abnormal cell differentiation with the development of cholangiocarcinoma. Parasitic infections and bile duct stone disease in Eastern countries and primary sclerosing cholangitis in the West are the main predisposing factors. The tripod for diagnosis is made up of ultrasound, computerized axial tomography and nuclear magnetic resonance. Conclusions: Hilar cholangiocarcinoma is a rare cause of cholestasis among the general population, with a predominance during the sixth decade of life and among males, jaundice being the reason for consultation of these patients, in which ultrasound and computerized axial tomography play the most important elements for its diagnosis, while the TNM and Bismuth-Corlette classification are essential for the correct planning of treatment(AU)

Intraductal papillary neoplasia of the bile duct (IPNB): case report and literature review

ABSTRACT Intraductal papillary neoplasm of the bile duct (IPNB) is a rare premalignant condition, defined as an epithelial neoplasm of the bile duct with exophytic papillary growth that can develop in any segment of the biliary tree. This pathology, with the highest prevalence in Asia, has been associated with the presence of hepatolithiasis and eastern liver infection (clonorchiasis). The diagnosis will depend on the clinical suspicion against the findings evidenced in the different diagnostic supports (invasive and non-invasive). Curative resection with negative margins is the treatment of choice in patients candidates for surgical management. In the event that the patient is not a candidate for curative resection, palliative treatment includes chemotherapy, percutaneous and endoscopic drainage, laser cholangioscopy ablation and intraluminal therapy with iridium 192. We present two cases of two patients with a diagnosis of IPNB confirmed by histology treated at our institution. The first case in an 86-year- old patient had a history of recurrent obstructive biliary syndrome and clinical suspicion of a new episode of cholangitis, and the second case in a 73-year-old patient who had a disseminated infectious process (spondylodiscitis, pelvic and intra-abdominal abscesses), and with the clinical suspicion of presenting a primary hepatobiliary focus. Both patients underwent single-operator cholangioscopy plus biopsy, confirming the diagnosis by histology. The first case was managed with palliative intent, indicating endoscopic diversion of the bile duct, while surgical management was indicated in the second case.

RESUMEN La neoplasia papilar intraductal de la vía biliar (NPIB) es una enfermedad premaligna poco frecuente, definida como una neoplasia epitelial de la vía biliar con crecimiento papilar exofítico que puede desarrollarse en cualquier segmento de la vía biliar. Esta patología, de mayor prevalencia en Asia, se ha asociado a la presencia de hepatolitiasis e infección hepática oriental (clonorquiasis). El diagnóstico dependerá de la sospecha clínica frente a los hallazgos evidenciados en los diferentes soportes diagnósticos (invasivos y no invasivos). La resección curativa con márgenes negativos es el tratamiento de elección en pacientes candidatos a manejo quirúrgico. En el caso de que el paciente no sea candidato a resección curativa, el tratamiento paliativo incluye quimioterapia, drenaje percutáneo y endoscópico, ablación por colangioscopia láser y terapia intraluminal con iridio 192. Presentamos dos casos de dos pacientes con diagnóstico de NPIB confirmado por histología tratado en nuestra institución. El primer caso de un paciente de 86 años con antecedentes de síndrome biliar obstructivo recurrente y cursando con un nuevo episodio y sospecha de colangitis aguda, y el segundo caso en un paciente de 73 años que presentaba un proceso infeccioso diseminado (espondilodiscitis, abscesos pélvicos e intraabdominales), con sospecha clínica de presentar un foco hepatobiliar primario. Ambos pacientes fueron sometidos a colangioscopia más biopsia, confirmando el diagnóstico por histología. El primer caso se manejó con intención paliativa, indicando derivación endoscópica de la vía biliar, mientras que en el segundo se indicó manejo quirúrgico.

Tumor de Klatskin y metástasis cerebral como presentación inusual en cáncer de mama / Klatskin tumor and brain metastasis in a breast cancer patient: Case report

Introducción: El cáncer de mama es la principal causa de muerte en mujeres a nivel mundial, se los clasifica en base a la expresión del receptor de estrógenos, de progesterona y de ERBB2. El tumor de Klatskin es infrecuente y se origina en la bifurcación del conducto biliar extrahepático. Presentación del caso: Paciente femenina de 60 años con diagnóstico de cáncer de mama estadío IIIB, que presenta hemiplejía derecha secundaria a lesión cerebral metastásica, inicialmente catalogada como neurocisticercosis. Después de 1 año 7 meses desarrolla ictericia colestásica cuya evaluación clínica permite evidenciar tumor de Klatskin mediante colangioresonancia. Discusión: El presente caso muestra una paciente con múltiples metástasis secundarias a cáncer de mama. Incluyendo, de igual manera, un tumor de Klatskin, el cual fue descubierto posterior a un síndrome colestásico. Son pocos los casos de la literatura que registran procesos metastásicos hacia conductos biliares con origen en un carcinoma ductal infiltrante. Conclusiones: Pocos casos en la literatura registran procesos metastásicos hacia las vías biliares con origen en infiltración ductal carcinoma; sin embargo, es fundamental informar para la evidencia clínica y el estudio de la literatura.

Introduction: Breast cancer is the principal cause of death in women worldwide, classi ed based on the expression of estrogen receptor, progesterone, and ERBB2. Klatskin tumor is rare and originates in the bifurcation of the extrahepatic bile duct. Case presentation: A 60 years old female patient diagnosed with stage IIIB breast cancer presents right hemiplegia secondary to metastatic brain injury, initially classi ed as neurocysticercosis. After one year and seven months, she developed cholestatic jaundice, whose clinical evaluation allows Klatskin tumor evidence through cholangioresonance. Discussion: The present case is about a patient with multiple metastases secondary to breast cancer. Including, in the same way, a Klatskin tumor, which was discovered after a cholestatic syndrome. Conclusions: Few cases in the literature register metastatic processes towards bile ducts originating from in ltrating ductal carcinoma; however, it is essential to report for clinical evidence and study of the literature.

Pathological and immunohistochemical aspects of primary hepatobiliary neoplasms in cats / Aspectos patológicos e imuno-histoquímicos de neoplasias hepatobiliares primárias em gatos

Primary hepatobiliary neoplasms (PHN) are uncommon in cats, and originate in hepatocytes, intra- and extrahepatic bile ducts, mesenchymal cells, and cells of neuroendocrine origin. The aim of this study was to determine the frequency of PHN in cats diagnosed in the metropolitan region of Porto Alegre (RS), Brazil, for a period of 17 years, determining their epidemiological, anatomopathological and immunohistochemical aspects. Necropsy reports of 2.090 cats were analyzed, 125 were diagnosed with primary hepatobiliary diseases, of which 15 were cases of PHN, representing 12% of the specific hepatobiliary conditions and 0.7% of the necropsies. All PHN were malignant, of which 93.3% had epithelial origin and 6.7% presented mesenchymal origin. Cholangiocarcinoma was the most commonly diagnosed neoplasm, followed by hepatocellular carcinoma and hemangiosarcoma. In general, cats with no defined breed were the most affected. Concerning sex, 60% were females and 40% males. Age ranged from five to 18 years, with a mean age of 10.5 years (median of ten years). Grossly, cholangiocarcinoma and hemangiosarcoma were multinodular and hepatocellular carcinoma was massive. Microscopically, cholangiocarcinomas were arranged in acini and ducts, whereas hepatocellular carcinomas were arranged in solid sheets or trabeculae. On immunohistochemistry, cholangiocarcinomas, hepatocellular carcinomas, and hemangiosarcomas were positive for the antibodies CK 7, Hep Par-1, and vimentin and von Willebrand factor, respectively.(AU)

Neoplasias hepatobiliares primárias (NHP) são incomuns em gatos e se originam de hepatócitos, células dos ductos biliares intra e extra-hepáticos, células mesenquimais e ainda células de origem neuroendócrina. O objetivo do trabalho foi determinar a frequência das NHP em gatos diagnosticados na Região Metropolitana de Porto Alegre, no período de 17 anos, abordando seus aspectos epidemiológicos, anatomopatológicos e imuno-histoquímicos (IHQ). Foram analisados os laudos de necropsia de 2.090 gatos sendo que 125 foram diagnosticados com doenças hepatobiliares primárias, destes 15 foram casos de NHP, representando 12% das condições hepatobiliares específicas e 0,7% do total de necropsias. Todos os diagnósticos de NHP eram malignos, destes 93,3% apresentaram origem epitelial e 6,7% mesenquimal. Colangiocarcinoma foi a neoplasia mais diagnosticada, seguido do carcinoma hepatocelular e hemangiossarcoma. De uma maneira geral, os gatos sem raça definida foram os mais acometidos. Em relação ao sexo 60% eram fêmeas e 40% machos. A idade variou de cinco a 18 anos, com a idade média de 10,5 anos (mediana de 10 anos). Macroscopicamente o colangiocarcinoma e hemangiossarcoma eram multinodulares, e o carcinoma hepatocelular, maciço. À histologia, houve predomínio do arranjo acinar e ductal nos colangiocarcinomas e sólido, no carcinoma hepatocelular. Na IHQ os colangiocarcinomas foram reativos para CK 7, carcinoma hepatocelular para Hep Par-1 e hemangiossarcoma para vimentina e fator de von Willebrand.(AU)

Photodynamic therapy of extrahepatic cholangiocarcinoma using digital cholangioscopy / Terapia fotodinâmica em colangiocarcinoma extra-hepático utilizando colangioscopia digital

ABSTRACT Background: Cholangiocarcinoma is an aggressive neoplasm that usually requires palliative biliary drainage. Photodynamic therapy (PDT) has been described as a successful adjunct treatment to malignant biliary obstruction. Aim: To describe the use of digital cholangioscope to help provide laser light during biliary PDT session using locally developed light source. Method: Patient receives intravenous photosensitizer 24 h before the procedure. It starts with a regular duodenoscopy. After identification of the major papilla and retrograde cannulation, the digital cholangioscope is introduced into the common bile duct. Then, the cholangioscopic examination helps to identify the neoplastic stricture. Under direct visualization lighting catheter is advanced through the cholangioscope. Repositioning is recommended every centimeter to cover all strictured area. At the end of the procedure, a final cholangioscopy assesses the bile duct for the immediate result and adverse events. Result: This procedure was applied in one 82-year-old male due to obstructive jaundice in the last two months. EUS and ERCP revealed a severe dilation of the common bile duct associated with choledocholithiasis. Besides, was revealed dilation of hepatic duct up to a well-circumscribed hypoechoic solid mass measuring 1.8x2 cm compressing the common hepatic duct. The mass was deemed unresectable and the patient was referred for palliative treatment with PDT. He remained asymptomatic for three months. He perished due to complications 15 months after the PDT session. Conclusion: Digital cholangioscopy-guided biliary PDT is feasible and seems safe and effective as an adjunct modality in the palliation of extrahepatic cholangiocarcinoma.

RESUMO Racional: Colangiocarcinoma é neoplasia agressiva que geralmente exige drenagem biliar paliativa. A terapia fotodinâmica (TFD) tem sido descrita como tratamento adjunto bem-sucedido para tratar obstrução biliar maligna. Objetivo: Descrever o emprego do colangioscópio digital para ajudar a fornecer luz de laser durante sessão de TFD biliar usando fonte de luz desenvolvida localmente. Método: Paciente recebe fotossensibilizador intravenoso 24 h antes do procedimento que começa com duodenoscopia regular. Após a identificação da papila principal e da canulação retrógrada, o colangioscópio digital é introduzido no ducto biliar comum. Em seguida, o exame colangioscópico ajuda a identificar a estenose neoplásica. Sob visualização direta, o cateter de iluminação avança através do colangioscópio. Reposicionamento é feito a cada centímetro. Ao final colangioscopia avalia o ducto biliar quanto ao resultado imediato e a eventos adversos. Resultado: Este procedimento foi aplicado em um homem de 82 anos devido à icterícia obstrutiva nos últimos dois meses. EUS e CPRE revelaram dilatação grave do ducto biliar comum associada à coledocolitíase. Além disso, havia dilatação do ducto hepático até massa sólida hipoecóica bem circunscrita, medindo 1,8x2 cm, comprimindo o ducto hepático comum. Ela foi considerada irressecável e paciente encaminhado para tratamento paliativo com TFD que permaneceu assintomático por três meses. Morreu devido a complicações 15 meses após a sessão de TFD. Conclusão: A TFD biliar guiada por colangioscopia digital é viável e parece segura e eficaz como modalidade auxiliar na paliação de colangiocarcinoma extra-hepático.