The clinical value of serum GPC3 level in predicting recurrence of patients with primary hepatocellular carcinoma / 中华预防医学杂志

Objective: To investigate the clinical value of serum glypican-3 (GPC3) detection in predicting recurrence of primary hepatocellular carcinoma (HCC). Methods: Through univariate and multivariate logistic regression analysis, the patients pathologically diagnosed with HCC in our hospital from March 2019 to January 2021 were enrolled as the experimental group (n=113), and patients with follow-up time longer than 6 months were included in the prognosis group(n=64). At the same time,20 healthy individuals and 20 individuals with benign liver disease from the physical examination center were enrolled by simple random sampling as control group (n=40). The serum GPC3 and alpha-fetoprotein (AFP) levels were respectively detected by ELISA and chemiluminescence. Then, the study explored the influential factors of the recurrence in HCC patients and constructed the HCC-GPC3 recurrence predicting model by logistic regression. Results: In the research, the sensitivity of GPC3 for the diagnosis of HCC was 61.95% (70/113) and AFP was 52.21% (59/113), meanwhile, the specificity of GPC3 could reach 87.50% (35/40) and AFP was 90.00% (36/40),respectively; The serum GPC3 levels of HCC patients with progressive stage, tumor size≥3 cm, vascular cancer thrombosis and portal venous thromboembolism were significantly higher than that of HCC patients with early stage, tumor size<3 cm, vascular cancer thrombosis and portal venous thromboembolism (Z=2.677, 2.848, 2.995, 2.252, P<0.05), independent of different ages, presence or absence of ascites, peritoneal metastasis, cirrhosis, intrahepatic metastasis (Z=-1.535, 1.011, 0.963, 0.394, 1.510, P>0.05), respectively. Univariate analysis showed that there were no statistically significant differences between the recurrence group and the non-recurrence group in terms of different age, tumor size, presence or absence of vascular cancer thrombosis, ascites, peritoneal metastasis, cirrhosis and AFP levels (χ2=2.012, 0.119, 2.363, 1.041, 0.318, 0.360, Z=0.748, P>0.05); The ratio of those with the progressive stage, portal venous thromboembolism and intrahepatic metastasis and GPC3 levels were all higher in the recurrence group than in the non-recurrence group (χ2=4.338, 11.90, 4.338, Z=2.805, P<0.05).Including the above risk factors in the logistic regression model, the logistic regression analysis showed that the stage, the presence of portal venous thromboembolism,intrahepatic metastasis and GPC3 levels were correlated with the prognosis recurrence of HCC patients (Wald χ2 =4.421, 5.681, 4.995, 4.319, P<0.05), and the HCC-GPC3 recurrence model was obtained as: OcScore=-2.858+1.563×[stage]+1.664×[intrahepatic metastasis]+2.942×[ portal venous thromboembolism]+0.776×[GPC3]. According to the receiver operating characteristic curve(ROC), the area under the curve(AUC)of the HCC-GPC3 prognostic model was 0.862, which was better than that of GPC3 alone (AUC=0.704). The cut-off value of model SCORE was 0.699 (the cut-off value of GPC3 was 0.257 mg/L), furthermore, the total sensitivity and specificity of model were 83.3% and 82.4%, which were better than those of GPC3(60.0% and 79.4%).Kaplan-Meier showed that the median PFS was significantly shorter in HCC patients with high GPC3 levels (≥0.257 mg/L) and high values of the model SCORE (≥0.700) (χ2=12.73, 28.16, P<0.05). Conclusion: Besides diagnosing of HCC, GPC3 can may be an independent risk indicator for the recurrence of HCC and can more efficiently predicting the recurrence of HCC patients when combined with the stage, the presence or absence of intrahepatic metastasis and portal venous thromboembolism.

Hemangioendotelioma hepático infantil: presentación de un caso clínico / Infantile hepatic hemangioendothelioma: a clinical case

El hemangioendotelioma hepático del lactante es una patología rara y más aún que su forma de presentación tenga complicaciones graves y el paciente fallezca. Se presenta el caso clínico de una lactante menor de 3 meses de edad que ingresó al Servicio Desconcentrado Hospital Pediátrico Dr. Agustín Zubillaga con diagnóstico de intoxicación herbácea (hierbabuena) e íleo metabólico. La hepatomegalia fue el signo más llamativo en la exploración clínica asociado a valores elevados de alfafetoproteína sérica. Los hallazgos ecosonográficos y tomográficos reportaron múltiples lesiones redondeadas que impresionaron metástasis hepáticas. La paciente fallece a los 23 días de iniciada la enfermedad actual siendo el diagnóstico postmortem hemangioendotelioma cavernoso gigante hepático, Se concluye que en general el diagnóstico de esta enfermedad se puede plantear sin una confirmación histológica, particularmente en lactantes menores, cuando los hallazgos clínicos, analíticos e imagenológicos son muy sugestivos aun cuando hay excepciones como lo presentado en este caso clínico(AU)

Infantile hemangioendothelioma is a rare, usually benign, disease. We present a case of a 3-month-old infant who was admitted in the Servicio Desconcentrado Hospital Pediátrico Dr. Agustín Zubillaga with the diagnosis of herbaceous poisoning (peppermint) and metabolic ileus. Hepatomegaly was the most characteristic sign in clinical examination and was associated with elevated levels of alpha-fetoprotein. Echographic and tomographic findings revealed multiple rounded lesions that impressed liver metastases. The patient died 23 days after admission and the postmortem diagnosis showed giant hepatic cavernous hemangioendothelioma. Diagnosis of hemangioendothelioma usually can be done without histopathological confirmation, especially in infants, when clinical, laboratory and imaging features are very suggestive of this disease, however there are exceptions as the one presented in this case(AU)

Testicular mixed germ cell tumor presenting with seizure as the initial symptom: a case report and literature review

Abstract Most patients with testicular germ cell tumor present with a painless scrotal mass. We report a 19-year-old patient who presented with neurological complains. Rapid clinical progression to coma was noted during the staging work up. A diagnosis of testicular mixed germ cell tumor with multiorgan metastasis (lymph node, lung, liver and brain) was made. Patients with brain metastasis should receive chemotherapy alone or combined with surgery or radiotherapy. Because the clinical symptoms deteriorated quickly, surgery was used upfront followed by chemotherapy and radiotherapy for the brain tumor. After the first stage of treatment, the clinical symptoms, tumor markers and imaging findings were improved. The residual brain tumor was eliminated by chemotherapy, and only sparse degenerated tumor cells were noted in the brain tissue. Longer follow up is required to assess the impact of our treatment strategy.

Rendimiento diagnóstico de marcadores tumorales séricos convencionales en pacientes con sospecha clínica de cáncer primario metastásico a hígado / Conventional serum tumor markers in liver cancer. Retrospective analysis of 118 patients

Background: Conventional serum tumor markers (CSTM) are widely used for monitoring patients with cancer. However, their usefulness as a diagnostic tool is controversial in primary or metastatic liver cancer (PMLC). Aim: To evaluate the diagnostic performance of the most commonly requested CSTM in the diagnostic approach of PMLC. Material and Methods: Review of medical records of patients aged over 18 years with a liver biopsy, attended from 2005 to 2017 in a tertiary hospital and a regional cancer center in Colombia. The results of liver biopsies were compared with tumor markers such as carcinoembryonic antigen (CEA), alpha-fetoprotein (AFP), CA 19-9, CA 125 and prostate specific antigen (PSA) using a receiver operating characteristic (ROC) curve analysis. Results: We reviewed 2063 medical records and retrieved 118 eligible patients (59 cases and 59 controls, 70% males). Thirty percent had obstructive jaundice. There was heterogeneity in the amount of tumor markers requested according to medical criteria. Only CA 19-9 showed discriminative capacity (> 17.6 U/m), with a cut-off point lower than that reported in the literature and a sensitivity of 69.5%, specificity of 91.6%, a positive likelihood ratio (LR) of 8.32, and a negative LR of 0.33. Conclusions: Except for CA 19-9, tumor markers were not useful for the initial diagnostic approach in patients with suspected primary or metastatic malignant liver tumors.

Coriocarcinoma gástrico primario: reporte de caso / Primary gastric choriocarcinoma: case report

El coriocarcinoma gástrico primario (CGP) es un tumor extremadamente raro, altamente invasivo y de rápida diseminación hematógena. Presentamos el caso de una paciente de 57 años que inicia con cuadro de hematemesis y, progresivamente, se le suman episodios de melena, baja de peso y epigastralgia. Es derivada al Instituto Nacional de Enfermedades Neoplásicas en donde se le realizan gastroscopía y biopsia. Así, el análisis histológico reportó patrón sugestivo para CGP; el cual se confirmó al realizarle a la paciente los estudios por imágenes necesarios y llevar a cabo el análisis inmunohistoquímico para gonadotrofina coriónica humana y alfa feto proteína. Posteriormente, a la paciente se le realiza una gastrectomía radical D2 con preservación esplénica y de cola de páncreas. Lamentablemente, su evolución no fue favorable y fallece por la progresión de la enfermedad.

Primary gastric choriocarcinoma (PGC) is an extremely rare and highly invasive tumor with rapid hematogenous spread. We present the case of a 57-year-old female patient who started with hematemesis and progressive episodes of melena, weight loss and epigastralgia. It is derived from the National Institute of Neoplastic Diseases where gastroscopy and biopsy are performed. Histological analysis reported pattern suggestive of PGC; that was confirmed by immunohistochemical analysis for human chorionic gonadotrophin and fetal alpha protein. Subsequently, the patient underwent a radical D2 gastrectomy with splenic preservation and tail of the pancreas preservation. Unfortunately, her evolution was not favorable and died due to the progression of the disease.

Yolk sac primary tumor of mediastino: a rare case in a young adult / Tumor de saco vitelínico primário do mediastino: raro caso em um adulto jovem

ABSTRACT Germ cell tumors are rare neoplasms that mostly occur in the gonads, although they can also affect other body sites, especially the anterior mediastinum (50 to 70% of all extragonadal germ cell tumors). We report a case of a primary mediastinal yolk sac tumor, a rare and aggressive germ cell tumors subtype. This was a 38-year-old man who was admitted to Hospital do Servidor Público Estadual "Francisco Morato de Oliveira", complaining about dyspnea and dry cough for 1 year. The computed tomography scan of his chest revealed a large mass in the anterior mediastinum with heterogeneous enhancement to the contrast associated with pleural effusion. There were also high serum levels of alpha-fetoprotein. After neoadjuvant chemotherapy, the patient underwent surgical resection of the mass, followed by pathological examination, which confirmed a primary mediastinal yolk sac tumor, a nonseminomatous subtype of germ cell tumors. Primary mediastinal yolk sac tumors have poor prognosis, despite advances in therapy with surgical resection and cisplatin-based chemotherapy. This poor prognosis is due to the degree of invasion and unresectability in most patients by the time of the diagnosis.

RESUMO Os tumores de células germinativas são neoplasias raras que acometem mais frequentemente as gônadas, embora possam também ocorrer em outras localizações do corpo, destacando-se o mediastino anterior (50 a 70% de todos os tumores de células germinativas extragonadais). No presente artigo, relatamos um caso de tumor de saco vitelínico mediastinal primário, de subtipo raro e agressivo de tumor de células germinativas. Tratava-se de um homem, 38 anos, admitido no Hospital do Servidor Público Estadual "Francisco Morato de Oliveira", com quadro de dispneia e tosse seca há 1 ano. Na investigação clínica, foi solicitada tomografia computadorizada de tórax, que mostrou volumosa massa no mediastino anterior com realce heterogêneo ao meio de contraste associada a derrame pleural. Havia ainda aumento dos níveis séricos da alfafetoproteína. Após quimioterapia neoadjuvante pré-operatória, o paciente foi submetido à ressecção cirúrgica, seguida de estudo anatomopatológico da peça, no qual demonstrou tratar-se de um tumor de saco vitelínico primário do mediastino. Os tumores de saco vitelínicos primários do mediastino têm prognóstico reservado, apesar do avanço na terapêutica com a ressecção cirúrgica e a quimioterapia à base de cisplatina. Isto se deve ao grau de invasão e de irressecabilidade na maioria dos pacientes no momento do diagnóstico.

Is resection of hepatocellular carcinoma in the era of liver transplantation worthwile? A single center experience / Ressecção de carcinoma hepatocelular na era do transplante de fígado: vale a pena? Experiência de um único centro

ABSTRACT Background - Liver resection for hepatocellular carcinoma is a potentially curative therapeutic procedure that can be performed readily after its indication, without the need of a long waiting time and lower costs when compared to liver transplantation, being a good alternative in patients with preserved/good liver function. Objective - Evaluate long-term results of liver resection from a high volume single center for selected patients with hepatocellular carcinoma in a context of a long waiting list for liver transplant. Methods - One hundred and one patients with hepatocellular carcinoma, with a mean age of 63.1 years, and preserved liver function were submitted to liver resection. Clinical and pathological data were evaluated as prognostic factors. Mean follow-up was 39.3 months. Results - All patients had a single nodule and 57 (58.2%) patients were within the Milan criteria. The size of the nodule ranged from 1 to 24 cm in diameter. In 74 patients, liver resection was performed with the open approach and in 27 (26.7%) was done laparoscopically. Postoperative morbidity was 55.3% being 75.5% of the complications classified as Dindo-Clavien I and II and operative mortality was 6.9%. Five-year overall and disease free survival rates were 49.9% and 40.7%, respectively.After a log-rank univariate analysis, the levels of preoperative alpha-fetoprotein (P=0.043), CA19-9 (P=0.028), capsule invasion (P=0.03), positive margin (R1-R2) (P=0.004) and Dindo-Claviens' morbidity classification IV (P=0.001) were the only parameters that had a significant negative impact on overall survival. On the odds-ratio evaluation, the only significant factors for survival were high levels of alpha-fetoprotein (P=0.037), and absence of free margins (P=0.008). Conclusion - Resection, for selected cases, is a potentially curative treatment with acceptable morbidity and mortality and, in a context of a long waiting list for transplant, plays an important role for the treatment of hepatocellular carcinoma.

RESUMO Contexto - A ressecção do carcinoma hepatocelular é um procedimento terapêutico potencialmente curativo que pode ser realizado imediatamente após sua indicação, sem a necessidade de longo tempo de espera e com custos mais baixos quando comparado com o transplante hepático, sendo uma boa alternativa em pacientes com função hepática preservada. Objetivo - Avaliar os resultados a longo prazo da ressecção hepática em centro de alto volume cirúrgico para pacientes selecionados com carcinoma hepatocelular em um contexto de uma longa lista de espera para transplante de fígado. Métodos - Cento e um pacientes com carcinoma hepatocelular, com idade média de 63,1 anos, e função hepática preservada foram submetidos à ressecção hepática. Os dados clínicos e patológicos foram avaliados como fatores prognósticos. O seguimento médio foi de 39,3 meses. Resultados - Todos os pacientes apresentavam um único nódulo e 57 (58,2%) estavam dentro dos critérios de Milão. O tamanho do nódulo variou de 1 a 24 cm de diâmetro. Em 74 pacientes, a ressecção hepática foi realizada com a abordagem aberta e em 27 (26,7%) através de laparoscopia.A morbidade pós-operatória foi de 55,3%, sendo 75,5% das complicações classificadas como Dindo-Clavien I e II e a mortalidade operatória foi de 6,9%. As sobrevida global e livre de doença em 5 anos foram 49,9% e 40,7%, respectivamente. Depois de análise univariada log-rank, os níveis de alfa-fetoproteína no pré-operatório (P=0,043), CA19-9 (P=0,028), invasão de cápsula (P=0,03), margem positiva (R1-R2) (P=0,004) e classificação de morbidade de Dindo-Claviens tipo IV (P=0,001) foram os únicos parâmetros que tiveram um impacto negativo significativo na sobrevida global. Na avaliação de risco relativo (odds-ratio), os únicos fatores importantes para a sobrevivência foram altos níveis de alfa-fetoproteína (P=0,037), e ausência de margens livres (P=0,008). Conclusão - A ressecção hepática em casos seleccionados, é um tratamento potencialmente curativo com morbilidade e mortalidade aceitáveis e, num contexto de uma longa lista de espera para transplante, tem um papel importante para o tratamento do carcinoma hepatocelular.

Glypican-3 level assessed by the enzyme-linked immunosorbent assay is inferior to alpha-fetoprotein level for hepatocellular carcinoma diagnosis

BACKGROUND/AIMS: Glypican-3 (GPC3) protein is highly expressed in hepatocellular carcinoma (HCC) tissue. It has been suggested as a diagnostic biomarker, but its inconsistent performance means that it requires further assessment. We therefore investigated the diagnostic value of the plasma GPC3 level compared to the alpha-fetoprotein (AFP) level as a diagnostic biomarker of HCC. METHODS: We enrolled 157 consecutive patients with newly diagnosed HCC and 156 patients with liver cirrhosis (LC) as the control group. GPC3 plasma levels were measured using two commercially available enzyme-linked immunosorbent assays (ELISAs, named as Assay 1 and 2), and AFP levels were measured using an enzyme-linked chemiluminescent immunoassay. The diagnostic accuracy was analyzed using the receiver operating characteristics (ROC) curve. RESULTS: Plasma GPC3 levels in HCC patients were very low (0–3.09 ng/mL) in Assay 1, while only 3 of the 157 patients (1.9%) showed detectable GPC3 levels in Assay 2. The median GPC3 level was not significantly elevated in the HCC group (0.80 ng/mL) compared with the LC group (0.60 ng/mL). The area under the ROC curve (AUC) for GPC3 was 0.559 in Assay 1. In contrast, the median AFP level was significantly higher in HCC (27.72 ng/mL) than in LC (4.74 ng/mL), with an AUC of 0.729. CONCLUSION: The plasma level of GPC3 is a poor diagnostic marker for HCC, being far inferior to AFP. The development of a consistent detection system for the blood level of GPC3 is warranted.

Peri-Transplant Change in AFP Level: a Useful Predictor of Hepatocellular Carcinoma Recurrence Following Liver Transplantation

Pretransplant alpha-fetoprotein (AFP) is a useful tumor marker predicting recurrence of hepatocellular carcinoma (HCC). Little is known, however, about the relationship between changes in AFP concentration and prognosis. This study investigated the clinical significance of change in peri-transplant AFP level as a predictor of HCC recurrence. Data from 125 HCC patients with elevated pretransplant AFP level who underwent liver transplantation (LT) between February 2000 and December 2010 were retrospectively reviewed. Patients with AFP normalization within 1 month after LT were classified into the rapid normalization group (n = 97), with all other patients classified into the non-rapid normalization group (n = 28). Tumor recurrence was observed in 17 of the 97 patients (17.5%) with rapid normalization; of these, 11 patients had high AFP levels and six had normal levels at recurrence. In contrast, tumor recurrence was observed in 24 of the 28 patients (85.7%) without rapid normalization, with all 24 having high AFP levels at recurrence. Multivariate analysis showed that non-rapid normalization (harzard ratio [HR], 4.41, P < 0.001), sex (HR, 3.26, P = 0.03), tumor size (HR, 1.15, P = 0.001), and microvascular invasion (HR, 2.65, P = 0.005) were independent risk factors for recurrence. In conclusion, rapid normalization of post-LT AFP level at 1 month is a useful clinical marker for HCC recurrence. Therefore, an adjuvant strategy and/or intensive screening are needed for patients who do not show rapid normalization.

Transarterial chemoembolization versus resection for intermediate-stage (BCLC B) hepatocellular carcinoma

BACKGROUND/AIMS: Several studies have suggested that surgical resection (SR) can provide a survival benefit over transarterial chemoembolization (TACE) for hepatocellular carcinoma (HCC) at the intermediate stage according to the Barcelona Clinic Liver Cancer (BCLC) staging system. However, the criteria for SR remain to be determined. This study compared the long-term outcome of intermediate-stage HCC patients treated by either TACE or SR as a primary treatment modality, with the aim of identifying the patient subgroup that gained a survival benefit by either modality. METHODS: In total, 277 BCLC intermediate-stage HCC patients treated by either TACE (N=225) or SR (N=52) were analyzed. RESULTS: The overall median survival time was significantly better for SR than TACE (61 vs. 30 months, P=0.002). Decision-tree analysis divided patients into seven nodes based on tumor size and number, serum alpha-fetoprotein (AFP) level, and Child-Pugh score, and these were then simplified into four subgroups (B1-B4) based on similarities in the overall hazard rate. SR provided a significant survival benefit in subgroup B2, characterized by ‘oligo' (2-4) nodules of intermediate size (5-10 cm) when the AFP levels was <400 ng/ml, or ‘oligo' (2-4) nodules of small to intermediate size (<10 cm) plus a Child-Pugh score of 5 when the AFP level was ≥400 ng/mL (median survival 73 vs. 28 months for SR vs. TACE respectively; P=0.014). The survival rate did not differ significantly between SR and TACE in the other subgroups (B1 and B3). CONCLUSIONS: SR provided a survival benefit over TACE in intermediate-stage HCC, especially for patients meeting certain criteria. Re-establishing the criteria for optimal treatment modalities in this stage of HCC is needed to improve survival rates.

Bone marrow metastasis presenting as bicytopenia originating from hepatocellular carcinoma

The bone is a common site for metastasis in hepatocellular carcinoma (HCC). However, bone marrow metastasis from HCC is rarely reported, and its frequency is unclear. Here we report a rare case of bone marrow metastasis that presented as bicytopenia originating from HCC without bone metastasis. A 58-year-old man was admitted for investigation of a liver mass with extensive lymph node enlargement that was detected when examining his general weakness and weight loss. Laboratory findings revealed anemia, thrombocytopenia, mild elevated liver enzymes, normal prothrombin time percentage and high levels of tumor markers (α-fetoprotein and des-γ-carboxyprothrombin). Abdominal computed tomography showed multiple enhanced masses in the liver and multiple enlarged lymph nodes in the abdomen. A bone marrow biopsy revealed only a few normal hematopoietic cells and abundant tumor cells. Despite its rarity, bone marrow metastasis should always be suspected in HCC patients even if accompanied by cirrhosis.

Feasibility of alpha-fetoprotein as a diagnostic tool for hepatocellular carcinoma in Korea

BACKGROUND/AIMS: The aim of this study was to evaluate the feasibility of alpha-fetoprotein (AFP) as a diagnostic tool for hepatocellular carcinoma (HCC) in Korean patients. METHODS: We retrospectively reviewed the medical records of HCC and cirrhosis patients at three hospitals. For each HCC patient, a cirrhosis patient matched for age, sex, etiology, and Child-Pugh classification was selected by simple random sampling. The performance of AFP in the diagnosis of HCC was determined using receiver operating characteristic curve analysis. RESULTS: A total of 732 patients with HCC or cirrhosis were selected for each case and the control groups. The mean age was 54 years, and 72.4% of patients were male. The mean serum AFP levels in the HCC group and cirrhosis group were 3,315.6 and 117.2 ng/mL, respectively (p < 0.001). The area under the receiver operating characteristic curve for all HCC patients was 0.757. The sensitivity, specificity, and positive predictive value of AFP was 50.55%, 87.70%, and 80.43%, respectively, at a cut-off of 20 ng/mL; 37.70%, 95.90%, and 90.20%, respectively, at a cut-off of 100 ng/mL, and 30.05%, 97.27%, and 91.67%, respectively, at a cut-off of 200 ng/mL. A cut-off of 100 ng/mL was more sensitive than one of 200 ng/mL with equivalent specificity and positive predictive value. CONCLUSIONS: The cut-off AFP value for early-stage HCC was 17.4 ng/mL. Our study cautiously suggests that AFP has a role in the diagnosis of HCC, and that the appropriate value of AFP for the diagnosis of HCC may be 100 ng/mL rather than 200 ng/mL.

A concise review of updated guidelines regarding the management of hepatocellular carcinoma around the world: 2010-2016

Many guidelines for hepatocellular carcinoma (HCC) have been published and updated globally. In contrast to other cancers, there is a range of treatment options for HCC involving several multidisciplinary care of the patient. Consequently, enormous heterogeneity in management trends has been observed. To support standard care for HCC, we systematically appraised 8 current guidelines for HCC around the world, including 3 guidelines from Asia, 2 from Europe, and 3 from the United States according to the selection criteria of credibility influence and multi-faceted. After a systematic appraisal, we found that these guidelines have both similarities and dissimilarities in terms of surveillance and treatment allocation recommendations due to regional differences in disease and other variables (diagnosis, staging systems) secondary to the lack of a solid, high level of evidence. In contrast to other tumors, the geographic differences in tumor biology (i.e., areas of increased hepatitis B prevalence) and available resources (organ availability for transplantation, medical technology, accessibility to treatment, health systems, and health resources) make it impractical to have an internationally universal guideline for all patients with HCC. Although Barcelona-Clinic Liver Cancer (BCLC) has long been dominant system for treatment-guiding staging of HCC, many Asia-pacific experts do not fully agree with its principle. The concepts of BCLC, for surgical resection or other locoregional therapy, are considered too conservative. Asian guidelines represent consensus about surgical resection and TACE indication for more advanced tumor.

Diagnóstico prenatal de tumor de células de la granulosa de tipo juvenil / Prenatal diagnosis of juvenile granulosa cell tumor

Presentamos un caso clínico de diagnóstico prenatal de una masa testicular. Tras el nacimiento, se realizó la exéresis del tumor y el análisis anatomopatológico determinó que se trataba de un tumor de células de la granulosa juvenil. Los tumores testiculares son raros y deben considerarse en el diagnóstico diferencial de las masas escrotales en los neonatos. El tumor de células de la granulosa juvenil es una entidad clínico-patológica poco frecuente, que representa el 5% de los tumores testiculares prepuberales. Se considera una neoplasia benigna y la orquiectomía es una técnica quirúrgica curativa.

We report a case of a prenatally diagnosed testis tumor. After delivery, it was decided to perform right radical orchiectomy which was subsequently diagnosed as a juvenile granulosa cell tumor. Neonatal testicular tumors are rare and should be considered in the differential diagnosis of newborn scrotal masses. Juvenile granulosa cell tumor is a rare benign neoplasm of the testicular stroma that accounts for 5% of all prepuberal testis tumors. As a benign neoplasm, orchiectomy is sufficient for treatment.

Prevalence of Burnout Syndrome in Patients Admitted with Acute Coronary Syndrome / Prevalência da Síndrome de Burnout em Pacientes Hospitalizados com Síndrome Coronariana Aguda

Background: Burnout Syndrome is the extreme emotional response to chronic occupational stress, manifesting as physical and mental exhaustion. Although associated with higher prevalence of cardiovascular risk factors, no study so far has evaluated whether the Burnout Syndrome could be a prevalent factor in non-elderly individuals active in the labor market, admitted for acute coronary syndrome (ACS). Objective: To evaluate the prevalence of the Burnout Syndrome in non-elderly, economically active patients, hospitalized with ACS. Methods: Cross-sectional study conducted in a tertiary and private cardiology center, with economically active patients aged <65 years, hospitalized with diagnosis of ACS. The Burnout Syndrome was evaluated with the Burnout Syndrome Inventory (BSI), which assesses workplace conditions and four dimensions that characterize the syndrome: emotional exhaustion (EE), emotional distancing (EmD), dehumanization (De) and professional fulfillment (PF). The Lipp’s Stress Symptoms Inventory for Adults (LSSI) was applied to evaluate global stress. Results: Of 830 patients evaluated with suspected ACS, 170 met the study criteria, 90% of which were men, overall average age was 52 years, and 40.5% had an average income above 11 minimum wages. The prevalence of the Burnout Syndrome was 4.1%. When we evaluated each dimension individually, we found high EE in 34.7%, high De in 52.4%, high EDi in 30.6%, and low PF in 5.9%. The overall prevalence of stress was 87.5%. Conclusion: We found a low prevalence of Burnout Syndrome in an economically active, non-elderly population among patients admitted for ACS in a tertiary and private hospital. .

Fundamento: Síndrome de Burnout (SB) é a resposta emocional extrema ao estresse crônico ocupacional, manifestando-se como processo de esgotamento físico e psíquico. Embora associada com maior prevalência de fatores de risco, nenhum estudo avaliou até o momento se a SB poderia ser um fator prevalente em indivíduos não idosos, ativos no mercado de trabalho, admitidos por síndrome coronária aguda (SCA). Objetivo: Avaliar a prevalência da SB em pacientes economicamente ativos, não idosos, hospitalizados com diagnóstico de SCA. Métodos: Estudo transversal realizado em um centro de cardiologia terciário e privado, com pacientes economicamente ativos, com idade < 65 anos, hospitalizados com diagnóstico de SCA. Para avaliação da SB, aplicou-se o Inventário da Síndrome de Burnout (ISB), que avalia as condições do ambiente de trabalho e as dimensões que caracterizam a SB: exaustão emocional (EE), distanciamento emocional (DEm), desumanização (Des) e realização profissional (RP). Aplicou-se ainda o Inventário de Sintomas de Stress para Adultos de Lipp (ISSL) para avaliação de estresse global. Resultados: Dos 830 pacientes avaliados com suspeita de SCA, 170 preencheram os critérios do estudo, sendo 90% homens, com idade média de 52 anos, e rendimento médio acima de 11 salários mínimos em 40,5% da amostra. A prevalência da SB foi de 4,1%. Elevada EE esteve presente em 34,7%, elevado DEm em 52,4%, elevada Des em 30,6% e baixa RP em 5,9%. A prevalência de estresse geral foi de 87,5%. Conclusão: A SB foi pouco prevalente em pacientes ativos no mercado de trabalho, não idosos, e internados por SCA nesta amostra avaliada em um hospital cardiológico privado e terciário. .

Spontaneous Neoplastic Remission of Hepatocellular Carcinoma / 대한소화기학회지

We report on a case of a 57-year-old male who underwent a curative resection for hepatocellular carcinoma (HCC) with histological confirmation of a spontaneously necrotized tumor. Initial serum AFP level was 4,778 ng/mL. A 3.7 cm hyperechoic mass in segment 6 of the liver was observed on ultrasonography and dynamic contrast-enhanced liver MRI showed a 3.7x3.1 cm sized HCC. He was scheduled to undergo curative surgical resection under the clinical diagnosis of an early stage HCC (Barcelona Clinic Liver Cancer stage A). Without treatment, the serum AFP level declined rapidly to 50 ng/mL over five weeks. He underwent curative wedge resection of segment 6 of the liver. Histology revealed complete necrosis of the mass rimmed by inflamed fibrous capsule on a background of HBV-related cirrhosis with infiltration of lymphoplasma cells. Exact pathophysiology underlying this event is unknown. Among the proposed mechanisms of spontaneous neoplastic remission of HCC, circulatory disturbance and activation of host immune response offer the most scientific explanation for the complete histologic necrosis of HCC in the resected mass seen in our patient.

Long-term outcomes of patients with advanced hepatocellular carcinoma who achieved complete remission after sorafenib therapy

BACKGROUND/AIMS: Sorafenib is currently the sole molecular targeted agent that improves overall survival in advanced hepatocellular carcinoma (HCC). Despite the efficacy of sorafenib, the response rate varies in patients with advanced HCC. We retrospectively analyzed a series of Korean patients with advanced HCC with complete remission (CR) after sorafenib therapy. METHODS: In total, 523 patients with advanced HCC were treated with sorafenib in 3 large tertiary referral hospitals in Korea. A survey was conducted to collect data on patients who experienced CR after sorafenib monotherapy, and their medical records and follow-up data were analyzed. The tumor response and recurrence rates were assessed by radiologic study, based on modified response evaluation criteria in solid tumors. RESULTS: Seven patients with advanced HCC experienced CR after sorafenib therapy. The median time to tumor disappearance and the median disease-free survival time were 3 months and 9 months, respectively. HCC recurrence was identified in three cases (42.9%). Of these, two patients discontinued sorafenib before or after achieving CR and the other patient continued sorafenib after achieving CR. HCC recurred at 3, 10, and 42 months after CR in these three patients. Three patients needed dose reduction for toxicity and adverse events. CONCLUSIONS: Though CR was achieved after sorafenib therapy in patients with advanced HCC, the recurrence rate was relatively high. Subsequent strategies to reduce a chance of recurrence after sorafenib therapy are required to investigate.

Serum Dickkopf-1 as a Biomarker for the Diagnosis of Hepatocellular Carcinoma

PURPOSE: Dickkopf-1 (DKK-1) is a Wnt/beta-catenin signaling pathway inhibitor. We investigated whether DKK-1 is related to progression in hepatocellular carcinoma (HCC) cells and HCC patients. MATERIALS AND METHODS: In vitro reverse-transcription polymerase chain reaction (RT-PCR), wound healing assays, invasion assays, and ELISAs of patient serum samples were employed. The diagnostic accuracy of the serum DKK-1 ELISA was assessed using receiver operating characteristic (ROC) curves and area under ROC (AUC) analyses. RESULTS: RT-PCR showed high DKK-1 expression in Hep3B and low in 293 cells. Similarly, the secreted DKK-1 concentration in the culture media was high in Hep3B and low in 293 cells. Wound healing and invasion assays using 293, Huh7, and Hep3B cells showed that DKK-1 overexpression promoted cell migration and invasion, whereas DKK-1 knock-down inhibited them. When serum DKK-1 levels were assessed in 370 participants (217 with HCC and 153 without), it was significantly higher in HCC patients than in control groups (median 1.48 ng/mL vs. 0.90 ng/mL, p0.05). When three biomarkers were combined (DKK-1 plus AFP plus DCP), they showed significantly higher AUC (AUC=0.952) than single marker, DKK-1 plus AFP, or DKK-1 plus DCP (all p<0.001). CONCLUSION: DKK-1 might be a key regulator in HCC progression and a potential therapeutic target in HCC. Serum DKK-1 could complement the diagnostic accuracy of AFP and DCP.

Sarcomatoid hepatocellular carcinoma with mixed osteoclast-like giant cells and chondroid differentiation

No abstract available.

Impact of immunosuppressant therapy on early recurrence of hepatocellular carcinoma after liver transplantation

BACKGROUND/AIMS: The most commonly used immunosuppressant therapy after liver transplantation (LT) is a combination of tacrolimus and steroid. Basiliximab induction has recently been introduced; however, the most appropriate immunosuppression for hepatocellular carcinoma (HCC) patients after LT is still debated. METHODS: Ninety-three LT recipients with HCC who took tacrolimus and steroids as major immunosuppressants were included. Induction with basiliximab was implemented in 43 patients (46.2%). Mycophenolate mofetil (MMF) was added to reduce the tacrolimus dosage (n=28, 30.1%). The 1-year tacrolimus exposure level was 7.2 +/- 1.3 ng/mL (mean +/- SD). RESULTS: The 1- and 3-year recurrence rates of HCC were 12.9% and 19.4%, respectively. Tacrolimus exposure, cumulative steroid dosages, and MMF dosages had no impact on HCC recurrence. Induction therapy with basiliximab, high alpha fetoprotein (AFP; >400 ng/mL) and protein induced by vitamin K absence/antagonist-II (PIVKA-II; >100 mAU/mL) levels, and microvascular invasion were significant risk factors for 1-year recurrence (P<0.05). High AFP and PIVKA-II levels, and positive 18fluoro-2-deoxy-d-glucose positron-emission tomography findings were significantly associated with 3-year recurrence (P<0.05). CONCLUSIONS: Induction therapy with basiliximab, a strong immunosuppressant, may have a negative impact with respect to early HCC recurrence (i.e., within 1 year) in high-risk patients.