Trastornos de la coagulación: factor V Leiden, panorama biológico, clínico y epidemiológico / Coagulation Disorders: Factor V Leiden, Biological, Clinical, and Epidemiological Overview

Resumen El sistema de coagulación mantiene la sangre en estado fluido en todo momento y, por tanto, está incesantemente activa durante toda la vida. Sin embargo, en el momento en que ocurre una lesión del sistema vascular, el sistema de coagulación inmediatamente gira 180° y transforma la sangre en un cuerpo sólido perfectamente localizado, al que llamamos coágulo. Este proceso, mediante el cual se forma un coágulo, se conoce como hemostasia, que es uno de los componentes del sistema de coagulación. La importancia de la mutación Leiden del factor V se basa en lo siguiente: el factor V de la coagulación es una proteína que se sintetiza en el hígado y el gen que lo codifica está situado en la región 23 del brazo largo del cromosoma 1, este factor circula en sangre periférica de manera inactiva hasta que interactúa con el factor X activado, formando un complejo que convierte al factor II (protrombina) en trombina, que va a tener su acción sobre el fibrinógeno convirtiéndolo en fibrina. La regulación del factor V activado se da por la actividad de la proteína C activada, cuando el factor V tiene una mutación (nombrada Leiden) que es ocasionada por el cambio de una adenina por una guanina en el nucleótido 1691 del factor V (G1691A), que causa que se sustituya una arginina por una glutamina en el residuo 506 de la proteína factor V; la proteína resultante es un factor V anómalo, mismo que no puede inactivarse por la proteína C activada, por lo que el factor V continúa activado y no puede impedir que el proceso de coagulación se detenga. En nuestro país (considerando varias afecciones) se ha descrito en diversas publicaciones de investigadores mexicanos que las mutaciones Leiden del factor V y la G20210A de la protrombina no son frecuentes, como lo son en los países europeos.

Abstract The coagulation system always keeps the blood in a fluid state and is therefore incessantly active throughout life. However, the moment an injury to the vascular system occurs, the coagulation system immediately rotates 180° and transforms the blood into a perfectly localized solid body, which we call a clot. This process, by which a clot forms, is known as hemostasis, which is one of the components of the coagulation system. The importance of the Leiden mutation of factor V is based on the following: coagulation factor V is a protein that is synthesized in the liver and the gene that encodes it is located in region 23 of the long arm of chromosome 1, this factor circulates in peripheral blood inactively until it interacts with activated factor X forming a complex that converts factor II (prothrombin) into thrombin, which will have its action on fibrinogen turning it into fibrin. The regulation of activated factor V is given by the activity of activated protein C, when factor V has a mutation (named Leiden) that is caused by the exchange of an adenine for a guanine in the nucleotide 1691 of factor V (G1691A), which causes arginine to be replaced by a glutamine in the 506 residue of the factor V protein, the resulting protein is an abnormal factor V, which cannot be inactivated by activated protein C, so factor V remains activated and cannot prevent the clotting process from stopping. In our country (considering several conditions) it has been described in various publications of Mexican researchers that Leiden mutations of factor V and G20210A of prothrombin are not frequent, as they are in European countries.

Metastatic papillary renal cell carcinoma with portal vein tumor thrombosis confirmed on blind liver biopsy

Portal vein tumor thrombosis (PVTT) is an uncommon condition in which tumor cells expand into the vessels, causing blood clot formation in the portal vein. PVTT is mainly associated with hepatocellular carcinoma, leading to an unfavorable prognosis; however, it can also develop in patients with other cancer types. Herein, we report a case of metastatic renal cell carcinoma diagnosed by a blind liver biopsy in a patient with dynamic computed tomography-confirmed portal vein thrombosis and cholangiopathy. This case illustrates the importance of systematic surveillance with routine laboratory tests and contrast-enhanced imaging studies on patients with cancer to detect potential liver infiltration of metastatic cancer.

Extrapulmonary manifestations and complications of severe acute respiratory syndrome coronavirus-2 infection: a systematic review

INTRODUCTION@#We aimed to describe the extrapulmonary manifestations of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection, including their frequency, onset with respect to respiratory symptoms, pathogenesis and association with disease severity.@*METHODS@#We searched the MEDLINE and Embase databases for SARS-CoV-2-related studies. Meta-analysis, observational studies, case series and case reports published in English or Chinese between 1 January 2020 and 1 May 2020 were included. Reports with only paediatric or obstetric cases were excluded.@*RESULTS@#169 articles were included. Early manifestations (preceding respiratory symptoms until Day 6 of onset) included olfactory and gustatory disturbance (self-reported in up to 68% and 85% of cases, respectively), gastrointestinal symptoms (up to 65.9%) and rash (up to 20.4%). From Day 7 onwards, hypercytokinaemia, paralleled multi-organ complications including acute cardiac injury (pooled incidence of 17.7% in 1,412 patients, mostly with severe disease and 17.4% mortality), kidney and liver injury (up to 17% and 33%, respectively) and thrombocytopenia (up to 30%). Hypercoagulability resulted in venous thromboembolic events in up to 31% of all patients. Uncommon disease presentation and complications comprised Guillain-Barré syndrome, rhabdomyolysis, otitis media, meningoencephalitis and spontaneous pneumomediastinum.@*CONCLUSION@#Although the systemic manifestations of SARS-CoV-2 infection are variegated, they are deeply interwoven by shared mechanisms. Two phases of extrapulmonary disease were identified: (a) an early phase with possible gastrointestinal, ocular and cutaneous involvement; and (b) a late phase characterised by multiorgan dysfunction and clinical deterioration. A clear, multidisciplinary consensus to define and approach thromboinflammation and cytokine release syndrome in SARS-CoV-2 is needed.

SpyGlass in Diagnosis of Hepatocellular Carcinoma with Right Hepatic Duct Tumor Thrombus Hemorrhage: A Case Report / 中国医学科学杂志(英文版)

Hepatocelluar carcinoma presenting as a biliary duct tumor thrombus is a relatively rare entity, with poor prognosis. The primary clinical manifestation of this disease is obstructive jaundice, which can often be misdiagnosed. A 59-year-old female patient was admitted with sudden onset of abdominal pain. Laboratory tests suggested obstructive jaundice, and enhanced magnetic resonance imaging of the upper abdomen did not show obvious biliary dilatation. Endoscopic ultrasound and endoscopic retrograde cholangiopancreatography suggested an occupying lesion in the upper bile duct. SpyGlass and biopsy finally confirmed hepatocellular carcinoma with right hepatic duct tumor thrombus hemorrhage. The SpyGlass Direct Visualization System, as an advanced biliary cholangioscopy device, showed the advantages of single-person operation as well as easy access to and visualization of the lesion.

A case report of Budd-Chiari syndrome with cardiac complications and low SPO2 successfully managed by an integrated-approach

Budd-Chiari syndrome [BCS] is a rare, potentially life-threatening condition characterized by the triad of abdominal pain, ascites, and hepatomegaly (with or without jaundice). There will be an underlying disorder in most cases. The diagnosis, as well as management of the case, requires a multidisciplinary approach. The treatment should aim at reducing the presenting symptoms as well as removing the underlying pathology. Here we explain a case report of a 21-year-old male patient in the subacute stage of BCS with its complications and considered as a candidate for liver transplantation. His liver enzymes, PT/INR, D- dimer, and homocysteine values were above normal levels. The arterial oxygen saturation level was subnormal, and he was on supportive oxygen supplement. Inferior venacava [IVC] Doppler revealed a non-obstructive intrahepatic thrombus. The patient was treated with Homoeopathic medicine Arsenicum album and Arnica montana, given as an adjuvant to conventional treatment.

Application of argatroban in patients receiving extracorporeal membrane oxygenation support: a case-control study / 中华危重病急救医学

Objective:To evaluate the safety and efficacy of argatroban applied as alternative anticoagulant in critical illness patients underwent extracorporeal membrane oxygenation (ECMO) with contraindications of unfractionated heparin (UFH), and to further explore the effective dose of argatroban.Methods:From July 1, 2013 to February 28, 2022, there were 14 patients who admitted in the respiratory intensive care unit (RICU) of Beijing Chao-Yang Hospital received ECMO and used argatroban for anticoagulation (argatroban group). Two of them received argatroban as the initial anticoagulant. The remaining 12 patients used UFH at first, and then switched to argatroban. UFH group included 28 patients who received UFH for anticoagulation after matching the demographic characteristics. Primary endpoint was the prevalence of ECMO-related thrombotic events. Secondary endpoints included the type of thrombotic events, prevalence of ECMO-related major bleeding events, bleeding sites, ICU mortality, mortality during ECMO, liver and kidney function, thrombelastogram, blood transfusion, dosage of argatroban, the dynamic changes of coagulation variables 4 days before and 7 days after argatroban treatment.Results:In argatroban group, there were 8 patients received veno-venous ECMO (VV-ECMO), 2 patients with veno-arterial ECMO (VA-ECMO), and 4 patients with veno-arterio-venous ECMO (VAV-ECMO). In UFH group, VV-ECMO was applied in 23 patients, VA-ECMO and VAV ECMO was established in 3 patients and 2 patients, respectively. In endpoint events, the incidence of ECMO related thrombotic events in argatroban group was slightly higher than that in UFH group (28.6% vs. 21.4%). The ECMO running time in argatroban group was slightly longer than that in UFH group [days: 16 (7, 21) vs. 13 (8, 17)]. The incidence of ECMO-related bleeding events (28.6% vs. 32.1%) and mortality during ECMO (35.7% vs. 46.4%) in argatroban group were slightly lower than those in UFH group. However, the differences were not statistically significant (all P < 0.05). The platelet transfusion in argatroban group was significantly higher than that in UFH group [U: 7.7 (0, 10.0) vs. 0.8 (0, 1.0)]. The coagulation reaction time (R value) in thrombelastography in argatroban group was significantly longer than that in UFH group [minutes: 9.3 (7.2, 10.8) vs. 8.8 (6.3, 9.7)]. The maximum width value [MA value, mm: 48.4 (40.7, 57.9) vs. 52.6 (45.4, 61.5)] and blood clot generation rate [α-Angle (deg): 54.1 (45.4, 62.0) vs. 57.9 (50.2, 69.0)] in the argatroban group were significantly lower than those in the UFH group (all P < 0.05). The activated partial thromboplastin time (APTT) was prolonged after changing from UFH to argatroban in the argatroban group [seconds: 63.5 (58.4, 70.6) vs. 56.7 (53.1, 60.9)]. The PLT level showed a decreasing trend during UFH anticoagulation therapy, and gradually increased after changing to argatroban. D-dimer level was 19.1 (7.0, 28.7) mg/L after switching to argatroban, and then no longer showed an increasing trend. The level of fibrinogen (FIB) showed a decreasing trend during the anticoagulant therapy of UFH (the lowest was 23.6 g/L), and fluctuated between 16.8 and 26.2 g/L after changing to argatroban. The median initial dose of argatroban was 0.049 (0.029, 0.103) μg·kg -1·min -1, which the highest dose was in VV-ECMO patients of [0.092 (0.049, 0.165) μg·kg -1·min -1]. The initial dose of VAV-ECMO was the lowest [0.026 (0.013, 0.041) μg·kg -1·min -1], but without significant difference ( P > 0.05). The maintenance dose of argatroban was 0.033 (0.014, 0.090) μg·kg -1·min -1, VV-ECMO patients was significantly higher than those in VA-ECMO and VAV-ECMO patients [μg·kg -1·min -1: 0.102 (0.059, 0.127) vs. 0.036 (0.026, 0.060), 0.013 (0.004, 0.022), both P < 0.05]. Conclusion:Argatroban appears to be a feasible, effective and safety alternative anticoagulant for patients with contraindications to UFH who undergoing ECMO support.

Role of thromboelastography in assessing the risk of spontaneous bleeding in patients with liver cirrhosis / 临床肝胆病杂志

ObjectiveTo investigate the association between thromboelastography (TEG) parameters and bleeding in patients with liver cirrhosis and whether TEG can be used to predict the risk of spontaneous bleeding in patients with liver cirrhosis, and to provide a basis for its preventive treatment. MethodsA retrospective analysis was performed for the clinical data of 174 patients with liver cirrhosis who attended Huadu People’s Hospital from May 2018 to April 2020 and did not receive invasive procedure, and according to the condition of bleeding, they were divided into non-bleeding group(n=64), gastrointestinal bleeding group(n=61), and mucocutaneous/oronasal bleeding group(n=49). The medical record system and laboratory information system were used to collect related information and laboratory test results for statistical analysis. The t-test was used for comparison of normally distributed continuous data between two groups; an analysis of variance was used for comparison between multiple groups, and the least significant difference t-test was used for further comparison between two groups. The Mann-Whitney U test was used for comparison of non-normally distributed continuous data between two groups, and the Kruskal-Wallis H test was used for comparison between multiple groups. MedCalc software was used for receiver operating characteristic (ROC) curve analysis, and the area under the ROC curve (AUC) was calculated for commonly used coagulation markers and TEG parameters in predicting the risk of bleeding in patients with liver cirrhosis. Cut-off value, sensitivity, specificity, positive predictive value, and negative predictive value were determined, and the Z test was used for comparison of indices in predicting mucocutaneous/oronasal bleeding. ResultsOf all 174 patients, 110 (63.2%) experienced spontaneous bleeding, among whom 61 (55.5%) had gastrointestinal bleeding and 49 (44.5%) had mucocutaneous/oronasal bleeding. There were significant differences in maximum amplitude (MA) and K between the bleeding group and the non-bleeding group (t=2.241 and -2.605, both P＜0.05). There were significant differences between the mucocutaneous/oronasal bleeding group and the non-bleeding/gastrointestinal bleeding groups in platelet count (PLT) and the TEG parameters of clot formation time, a-angle, MA, and coagulation index (CI) (F=3.947, H=12.867, F=4.007, F=8.498, F=5.420, all P＜0.05). Among the TEG parameters, reaction time and Lys30 were generally within the normal range, while there was a prolonged kinetics (K) time and reductions in a-angle, MA, and CI. PLT ≤40×109/L, MA ≤357 mm, K time ＞4.2 minutes, a-angle ≤51.6, and CI ≤-5.9 could be used to predict spontaneous mucocutaneous/oronasal bleeding in patients with liver cirrhosis (all AUC ＞0.7), with positive predictive values of 82.4, 88.9, 81.0, 72.7, and 73.7, respectively, and negative predictive values of 68.3, 72.5, 73.0, 69.4, and 66.7, respectively. ConclusionPLT and the TEG parameters of K time, a-angle, MA, and CI can predict spontaneous bleeding caused by abnormal coagulation in liver cirrhosis, while conventional coagulation parameters prothrombin time and activated partial thromboplastin time cannot predict such bleeding, which provides a basis for the treatment of coagulation disorder and transfusion of blood components for patients with liver cirrhosis.

Clinical, laboratory and anatomopathological study of caudal vena cava thrombosis in cattle / Estudo clínico, laboratorial e anatomopatológico da trombose da veia cava caudal em bovinos

This paper aimed to describe the main clinico-epidemiological, laboratory, and anatomopathological findings in 10 cattle affected with caudal vena cava thrombosis. The main clinical signs observed were decreased milk production, reduced appetite, apathy, impairment of ruminal motility, cardiorespiratory disorders (tachycardia and tachypnea), epistaxis, hemoptysis, and ascites. Intercurrent diseases such as mastitis, metritis, and phlebitis were verified. The hematological findings were mild anemia, leukocytosis due to neutrophilia with regenerative left shift, and hyperfibrinogenemia. The pathological exams revealed thrombi in the caudal vena cava, hepatomegaly, ascites, liver abscesses, pulmonary edema and emphysema, and abscesses in the lungs. The association of epidemiological information, clinical signs such as respiratory distress, epistaxis or hemoptysis, in addition to anemia and leukocytosis due to neutrophilia, as well as the occurrence of thrombus in the caudal vena cava as pathological findings, are indicative elements of the clinical picture of vena cava thrombosis in cattle. It is reiterated that this disease has an unfavorable prognosis and, when diagnosed, the animal must be culled.(AU)

Este trabalho teve por objetivo descrever os principais achados clínico-epidemiológicos, laboratoriais e anatomopatológicos de 10 bovinos diagnosticados com trombose da veia cava caudal. Os principais achados clínicos foram redução da produção leiteira, diminuição do apetite, apatia, comprometimento da dinâmica ruminal, alterações cardio-respiratórias (taquicardia e taquipnéia), epistaxe, hemoptise e ascite. Foi constatada a ocorrência de doenças intercorrentes como mastite, metrite e flebite. O hemograma revelou discreta anemia, leucocitose por neutrofilia com desvio para esquerda regenerativo e hiperfibrinogenemia. No exame anatomopatológico revelou trombos localizados na veia cava caudal, hepatomegalia, ascite e abscessos hepáticos; além de abscessos, enfisema e edema pulmonares. A associação de informações epidemiológicas, sinais clínicos como desconforto respiratório, epistaxe ou hemoptise, além de anemia e leucocitose por neutrofilia, bem como a ocorrência de trombo na veia cava caudal como achados patológicos são elementos indicativos do quadro clínico de trombose de veia cava em bovinos. Reitera-se que essa doença tem prognóstico desfavorável e, quando diagnosticada, o animal deve ser abatido.(AU)

Effects of Highly Active Antiretroviral Treatment on Liver and Kidney Functions

Aim:This study assesses the effects of HAART on liver and renal functions in HIV infected individuals on HAART.Study Design:Cross sectional study.Place and Methods:This study was conducted in Tamale, Ghana from August, 2015 to November 2017. Original Research Article Methodology:A total of 300 HIV infected participants with ages ranging from 19 to 79 years who have been administered with HAART for at least 6 months were recruited. Pre-HAART administration (baseline) demographic and clinical information, with initial liver and renal function test results were retrieved from the medical records of the participants present at the ART center. Post HAART administration blood sample (5mLs) was taken from each participant into a gel separated vacutainer tube, allowed to clot and spun at 3000rpm for 3 minutes to produce serum. The product (serum) was used for liver and renal function test analysis using a fully automated chemistry analyser (Vital Scientific Selectra Flexor XL). Results: Of the study population, 72% were administered with AZT/3TC/EFV, 13% with AZT/3TC/NVP, 6.7% with TDF/3TC/LPV/r and TDF/3TC/NVP, 1% with AZT/3TC/EFV while 0.7% were administered with TDF/FTC/EFV. The following parameters were significantly increased post HAART administration; ALT (25.53 ± 16.90 to 30.87 ± 19.28 U/L), ALP (163.7 ± 141.0 to 215.2 ± 143.4 U/L), GGT (37.27 ± 25.21 to 53.19 ± 41.71 U/L), Total protein (73.97 ± 17.08 to 82.31 ± 11.62 g/L), Albumin (38.02 ±9.331 to 41.01 ± 7.471 g/L), Globulin 38.02 ± 15.71 to 42.79 ± 25.20 (g/L). There were however significant reductions in Total bilirubin (12.13 ± 10.85 to 9.434 ± 4.560 μmol/L), Direct bilirubin (6.616 ± 5.770 to 4.184 ± 2.806 μmol/L), (Creatinine 73.19 ±36.13 to 63.14 ± 27.14 μmol/L) and Urea (3.515 ± 2.552 to 3.011±1.274 mmol/L).Conclusion: HAART improves renal function, induces elevation in liver enzymes, stimulates the production of plasma proteins and reduces serum bilirubin concentration

Contained rupture of a large right hepatic artery aneurysm: the ticking bomb within!

Hepatic artery aneurysms (HAAs) are rare and represents one fifth of visceral aneurysms. We report a case of a 75 year old female who presented to the outpatient department with complaints of abdominal pain and anorexia for 2 weeks. On examination the patient was stable, she had mild tenderness in the right hypochondrial region. Ultrasound abdomen showed an intrahepatic cystic area with both arterial and venous flow, suggesting the possibility of an intrahepatic arteriovenous malformation. Contrast-enhanced computed tomography abdomen showed a large right HAA with contained rupture and intra hepatic extension. She was posted for emergency laparotomy and was found to have a contained rupture a contained rupture of the right HAA of size 10×8 cm with intra hepatic extension. Right hepatectomy was done and the resected margin of liver showed a dilated cystic space with blood clot. Histopathological examination showed intrahepatic aneurysm with atherosclerosis and laminated luminal thrombus. Contained rupture of HAAs with intrahepatic extension are rare. Even though the prevalence of HAAs is low, the risk of rupture is reported to be as high as 20-80% and the mortality following spontaneous rupture is 40%. Hence an aggressive approach to the management of HAA is required whenever detected.

Viscoelastic coagulation test for liver transplantation

Coagulation and transfusion management in patients undergoing liver transplantation is challenging. Proper perioperative monitoring of hemostasis is essential to predict the risk of bleeding during surgery, to detect potential causes of hemorrhage in time, and to guide hemostatic therapy. The value of conventional coagulation test is questionable in the acute perioperative setting due to their long turnaround time and the inability to adequately reflect the complex changes in hemostasis in patients with liver disease. Viscoelastic coagulation tests provide simultaneous measurement of multiple aspects of whole-blood coagulation including plasmatic coagulation and fibrinolytic factors and inhibitors that reflect most aspects of hemostasis. Coagulation initiation, mechanical clot stability, and fibrinolysis can be estimated immediately using point-of-care techniques. Therefore, viscoelastic coagulation tests including ROTEM & TEG would be useful to guide patient blood management strategy during liver transplantation.

Presencia de trombosis y hallazgos anatomopatológicos post mortem en 109 pacientes con COVID-19 / Presence of thrombosis and post-mortem pathological findings in 109 patients with COVID-19

INTRODUCCIÓN: En 6 meses se notificaron más de 400 mil fallecidos por COVID-19. Han surgido múltiples investigaciones para comprender su etiopatogenia, siendo la autopsia médica uno de los mejores procedimientos para obtener información. Presentamos una revisión respecto a hallazgos post mortem publicados hasta mayo, 2020. RESULTADOS: Se recolectaron 12 estudios, de un total de 109 pacientes cuyo deceso fue por complicación respiratoria, predominó el sexo masculino, edad avanzada y con múltiples comorbilidades. El estudio PCR se realizó principalmente para diagnóstico. Se demostró ARN viral en riñón, hígado, corazón, cerebro y otros órganos. Los autores relataron presencia de micro y/o macro trombosis, en 50 de 109 casos, sobre todo a nivel pulmonar y renal, de tipo microscópica y relacionados a signos de shock. Desde la perspectiva anatomopatológica, se centra en alteraciones pulmonares y renales: daño alveolar difuso, injuria tubular aguda, microtrombos y otros signos de alteración microcirculatoria. Los estudios inmunohistoquímicos, de inmunofluoresencia y microscopía electrónica sugieren tropismo del virus por células epiteliales y estromales a nivel pulmonar y renal. En otros órganos se encuentran elementos morfológicos inespecíficos, atribuibles a patologías de base o shock. CONCLUSIÓN: El patrón histopatológico de daño alveolar difuso es frecuente, principalmente en fase exudativa o temprana. En el tejido renal destaca la injuria tubular aguda y daño microcirculatorio. El número y la descripción de muestras en otros órganos es reducida, siendo necesaria mayor casuística. La trombosis, es un trastorno prevalente en pulmones y riñones de pacientes con signos de shock. El tipo de trombo con más frecuencia descrito, es el microtrombo. Si bien se puede explicar como gatillante del fenómeno trombótico la interacción entre agente y huésped, otros factores deben ser estudiados para dilucidar la patogenia.

Risk factors associated with hepatic artery thrombosis: analysis of 1050 liver transplants / Fatores de risco associados à trombose de artéria hepática: análise de 1050 transplantes de fígado

ABSTRACT Background: Hepatic artery thrombosis is an important cause of graft loss and ischemic biliary complications. The risk factors have been related to technical aspects of arterial anastomosis and non-surgical ones. Aim: To evaluate the risk factors for the development of hepatic artery thrombosis. Methods: The sample consisted of 1050 cases of liver transplant. A retrospective and cross-sectional study was carried out, and the variables studied in both donor and recipient. Results: Univariate analysis indicated that the variables related to hepatic artery thrombosis are: MELD (p=0.04) and warm time ischemia (p=0.005). In the multivariate analysis MELD=14.5 and warm ischemia time =35 min were independent risk factors for hepatic artery thrombosis. In the prevalence ratio test for analysis of the anastomosis as a variable, it was observed that patients with continuous suture had an increase in thrombosis when compared to interrupted suture. Conclusions: Prolonged warm ischemia time, calculated MELD and recipient age were independent risk factors for hepatic artery thrombosis after liver transplantation in adults. Transplanted patients with continuous suture had an increase in thrombosis when compared to interrupted suture. Re-transplantation due to hepatic artery thrombosis was associated with higher recipient mortality.

RESUMO Racional: Trombose de artéria hepática é importante causa de falência de enxerto e complicações biliares. Fatores de risco para trombose estão relacionados aos aspectos técnicos da anastomose arterial e fatores não cirúrgicos. Objetivo: Avaliar os fatores de risco para o desenvolvimento de trombose de artéria hepática. Métodos: A amostra consta de 1050 casos de transplante hepático. Foi realizado estudo retrospectivo e transversal, e as variáveis foram avaliadas em doadores e receptores. Resultados: A análise univariada mostrou que as variáveis relacionadas a trombose de artéria hepática são: MELD e tempo de isquemia quente. Na análise multivariada, o MELD=14.5 e tempo de isquemia quente =35 min foram fatores de risco independentes para trombose de artéria hepática. No teste de prevalência para avaliação do tipo de anastomose como variável, foi observado que a sutura contínua tem maior risco de trombose quando comparada com aquela em pontos separados. Conclusão: Tempo de isquemia quente prolongado, MELD calculado e idade do recipiente foram fatores de risco independentes para trombose de artéria hepática após transplante de fígado em adultos. Pacientes submetidos à anastomose com sutura contínua apresentaram mais trombose quando comparados com a em pontos separados. Retransplante por trombose está associado com maior mortalidade.

Incidental detection of microfilaria in various autopsy specimens: A study at tertiary care hospital

Background: Autopsy examinations are necessary to rule out cause of death, and simultaneously, it also detects incidental pathologies which might not be a leading cause of death. Till date, no one has reported autopsy examination utility for the detection of microfilaria burden. In this retrospective study, we analyzed cases with incidental finding of asymptomatic cases of microfilaria. Objectives: Our main aim was to highlight its burden within the region of South Gujarat where filariasis is endemic despite various government programs to control and eradicate it. Materials and Methods: We have analyzed the autopsy reporting data during the period of January 2013–December 2013 from a tertiary care hospital of South Gujarat. Along with tissue section, we also processed blood clot from heart chambers for microscopic examination to confirm diagnosis. Results: A total of 19 cases of 607 autopsy cases showed the presence of microfilaria in various organs such as heart, lung, liver, spleen, kidney, and brain without any tissue reaction. All sections from blood clot showed the presence of circulating microfilaria in positive cases. Among all organ sections, we were able to get it most commonly in the heart interstitial spaces in majority of the cases. Conclusion: This study showed 3.1% prevalence of asymptomatic circulating microfilaria cases. This can be one of the ways to measure the prevalence of microfilaria in endemic regions as routine screening and diagnostic procedure has their known limitations. The technique to find microfilaria can be also strengthened by microscopic examination of blood clot from heart chamber or heart auricles.

Tumor estromal gastrointestinal como causa infrecuente de hemoperitoneo / Gastrointestinal Stromal Tumor as a Rare Cause for Hemoperitoneum

RESUMEN El tumor estromal gastrointestinal es el tumor mesenquimático más frecuente y se caracteriza por la expresión de un receptor de factor de crecimiento tirosina kinasa, CD117 c-KIT/CD 117. Se diferencia del resto de los tumores mesenquimáticos en que no expresa esta proteína. Alrededor del 70 - 80 por ciento de estos tumores son benignos, la mayoría se localizan en estómago e intestino delgado (> 90 por ciento). Los tumores estromal gastrointestinal malignos son generalmente de gran tamaño (> 5 cm), con índice mitótico alto y pueden dar metástasis a hígado y peritoneo. El tratamiento es la resección quirúrgica. Presentamos una paciente con 65 años de edad que acudió al cuerpo de guardia por sufrir caída de sus pies y quejarse de dolor abdominal. Como datos positivos al examen físico se constató palidez cutáneo mucosa y los complementarios de urgencia. El ultrasonido y la tomografía axial computarizada informaron líquido libre en cavidad con cifras de hemoglobina en 6,4 g/L. La punción abdominal constató sangre roja que no coagulaba. Se realizó laparotomía exploratoria encontrando hemoperitoneo y gran tumoración en cara anterior del antro gástrico, con otra pequeña en la porción alta del cuerpo; se realizó resección local con bordes libres de tumor y se suturaron los bordes gástricos. El resultado de la biopsia informó tumor del estroma gastrointestinal de células fusiformes con bajo índice mitótico, que midió 13 x 8 x 8 cm, con marcada angiogénesis y zonas de calcificación(AU)

ABSTRACT Gastrointestinal stromal tumor is the most frequent mesenchymal tumor and is characterized by expression of a tyrosine kinase growth factor receptor, CD117 c-KIT/CD 117. It is different to the rest of mesenchymal tumors in that it does not express this protein. About 70-80 percent of these tumors are benign. The majority are located in the stomach and small intestine (more than 90 percent). Malignant gastrointestinal stromal tumors are usually large (over 5 cm in size), with a high mitotic index, and can metastasize to the liver and peritoneum. The treatment is surgical resection. We present a 65-year-old patient who came to the emergency room due to having fallen on her own feet and complaining of abdominal pain. As positive data to the physical examination, mucous and skin whitening and the emergency complement tests were analyzed. Ultrasound and CT scan reported free fluid in cavity with hemoglobin values at 6.4 g/L. The abdominal puncture showed red blood that did not clot. The exploratory laparotomy showed a hemoperitoneum and a large tumor in the anterior face of the gastric antrum, with a small one in the upper portion of the body; local resection with tumor-free borders was performed and the gastric borders were sutured. The result of the biopsy reported a spindle cell gastrointestinal stromal tumor with a low mitotic index, measuring 13x8x8 cm, with marked angiogenesis and areas of calcification(AU)

Comparison of Radioembolization and Sorafenib for the Treatment of Hepatocellular Carcinoma with Portal Vein Tumor Thrombosis: A Systematic Review and Meta-Analysis of Safety and Efficacy

OBJECTIVE: To compare the safety and efficacy of radioembolization with that of sorafenib for the treatment of hepatocellular carcinoma (HCC) with portal vein tumor thrombosis (PVTT). MATERIALS AND METHODS: MEDLINE, EMBASE, and Cochrane databases were searched for studies reporting outcomes in patients with HCC and PVTT treated with radioembolization or sorafenib. Meta-analyses of cumulative overall survival (OS) and Kaplan-Meier survival rates according to the time to progression (TTP) and incidence of adverse events (AEs) were performed. Subgroup analyses were conducted on 1-year OS data. RESULTS: Seventeen studies were identified (four involving radioembolization, 10 involving sorafenib, and three comparing both). Pooled OS rates were higher in the radioembolization group, notably at 6 months {76% (95% confidence interval [CI], 64–85%) vs. 54% (95% CI, 45–62%)} and 1 year (47% [95% CI, 38–57%] vs. 24% [95% CI, 18–30%]); TTP was also longer with radioembolization. In patients undergoing radioembolization, the proportion of patients with Eastern Cooperative Oncology Group status 0 (p < 0.0001), Child-Pugh A (p < 0.0001), extrahepatic metastasis (p = 0.0012), and a history of cancer treatment (p = 0.0048) was identified as a significant source of heterogeneity for the 1-year OS. Radioembolization was associated with a lower incidence of grade 3/4 AEs than sorafenib (9% [95% CI, 3–27%] vs. 28% [95% CI, 17–43%]). CONCLUSION: Compared with sorafenib, radioembolization is a safer and more effective treatment for HCC with PVTT and is associated with prolonged survival, delayed tumor progression, and fewer grade 3/4 AEs.

Cystic Degeneration of Hepatocellular Carcinoma Mimicking Mucinous Cystic Neoplasm / 대한소화기학회지

Spontaneous regression of tumors is an extremely rare event in hepatocellular carcinoma (HCC) with only a few reports available. With the accumulation of clinical information and tumor immunogenetics, several mechanisms for the cystic changes of HCC have been suggested, including arterial thrombosis, inflammation, and rapid tumor growth. This paper reports an uncommon case of the partial regression of HCC, which was initially misdiagnosed as a mucinous cystic neoplasm of the liver due to the unusual radiologic findings. A 78-year-old female with the hepatitis B virus and liver cirrhosis presented with an approximately 5 cm-sized cystic mass of the liver. From the radiologic evidence of a papillary-like projection from the cyst wall toward the inner side, the initial impression was a mucinous cystic neoplasm of the liver. The patient underwent a surgical resection and finally, cystic degeneration of HCC, in which approximately 80% necrosis was noted. This case suggests that if a cystic neoplasm of liver appears in a patient with a high risk of HCC on a hepatobiliary imaging study, it is prudent to consider the cystic degeneration of HCC in a differential diagnosis.

Treatment Outcome after Fractionated Conformal Radiotherapy for Hepatocellular Carcinoma in Patients with Child-Pugh Classification B in Korea (KROG 16-05) / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: There is limited data on radiotherapy (RT) for hepatocellular carcinoma (HCC) in patients with Child-Pugh classification B (CP-B). This study aimed to evaluate the treatment outcomes of fractionated conformal RT in HCC patients with CP-B. MATERIALS AND METHODS: We retrospectively reviewed the data of HCC patients with CP-B treated with RT between 2009 and 2014 at 13 institutions in Korea. HCC was diagnosed by the Korea guideline of 2009, and modern RT techniques were applied. Fraction size was ≤ 5 Gy and the biologically effective dose (BED) ≥ 40 Gy₁₀ (α/β = 10 Gy). A total of 184 patients were included in this study. RESULTS: Initial CP score was seven in 62.0% of patients, eight in 31.0%, and nine in 7.0%. Portal vein tumor thrombosis was present in 66.3% of patients. The BED ranged from 40.4 to 89.6 Gy₁₀ (median, 56.0 Gy₁₀). After RT completion, 48.4% of patients underwent additional treatment. The median overall survival (OS) was 9.4 months. The local progression-free survival and OS rates at 1 year were 58.9% and 39.8%, respectively. In the multivariate analysis, non-classic radiation-induced liver disease (RILD) (p < 0.001) and additional treatment (p < 0.001) were the most significant prognostic factors of OS. Among 132 evaluable patients without progressive disease, 19.7% experienced non-classic RILD. Normal liver volume was the most predictive dosimetric parameter of non-classic RILD. CONCLUSION: Fractionated conformal RT showed favorable OS with a moderate risk non-classic RILD. The individual radiotherapy for CP-B could be cautiously applied weighing the survival benefits and the RILD risks.

Liver Transplantation after Successful Downstaging with Hepatic Arterial Infusion Chemotherapy in a Patient with Hepatocellular Carcinoma with Portal Vein Tumor Thrombus

Hepatocellular carcinoma (HCC) is one of the most common cancers worldwide. The majority of patients with HCC are diagnosed at advanced disease stages with vascular invasion, where curative approaches are often not feasible. Currently, sorafenib is the only available standard therapy for HCC with portal vein tumor thrombosis (PVTT). However, in many cases, sorafenib therapy fails to achieve satisfactory results in clinical practice. We present a case of advanced HCC with PVTT that was treated with hepatic arterial infusion chemotherapy (HAIC) followed by liver transplantation. Three cycles of HAIC treatment resulted in necrotic changes in most of the tumors, and PVTT was reduced to an extent at which liver transplantation was possible. Further studies are required to determine the treatment strategies for advanced HCC with PVTT that can improve prognosis.

Analysis of risk factors for portal vein thrombosis after liver resection

PURPOSE: We evaluated the risk factors for posthepatectomy thrombosis including portal vein thrombosis (PVT) and clinical outcomes. METHODS: We retrospectively analyzed 563 patients who had undergone hepatectomy from February 2009 to December 2014. Twenty-nine patients with preoperatively confirmed thrombosis and tumor recurrence-related thrombosis were excluded. We identified the location of the thrombosis as main portal vein (MPV), peripheral portal vein (PPV) and other site such as hepatic vein or inferior vena cava. Patients with MPV thrombosis and PPV thrombosis with main portal flow disturbance were treated with anticoagulation therapy. We performed operative thrombectomy before anticoagulation therapy who did combined portal vein (PV) segmental resection. RESULTS: Of the 534 patients, 22 (4.1%) developed posthepatectomy thrombosis after hepatectomy. Among them, 19 (86.4%) had PVT. The mean duration of Pringle's maneuver was significant longer in the PVT group than the no-thrombosis group (P = 0.020). Patients who underwent combined PV segmental resection during hepatectomy were more likely to develop posthepatectomy PVT (P = 0.001). Thirteen patients who had MPV thrombosis and PPV thrombosis with main portal flow disturbance received anticoagulation therapy immediately after diagnosis and all of them were improved. Among them, 2 patients who developed PVT at the PV anastomosis site after PV segmental resection, underwent operative thrombectomy before anticoagulation therapy and both were improved. There were no patients who developed complications related to anticoagulation therapy. CONCLUSION: Long duration of Pringle's maneuver and PV segmental resection were risk factors. Anticoagulation therapy or operative thrombectomy should be considered for PVT without contraindications.