Locally advanced hepatocellular carcinoma (HCC) with portal vein thrombosis carries a 1-year survival rate <10%. Localized concurrent chemoradiotherapy (CCRT), followed by hepatic arterial infusion chemotherapy (HAIC), was recently introduced in this setting. Here, we report our early experience with living donor liver transplantation (LDLT) in such patients after successful down-staging of HCC through CCRT and HAIC. Between December 2011 and September 2012, eight patients with locally advanced HCC at initial diagnosis were given CCRT, followed by HAIC, and underwent LDLT at the Severance Hospital, Seoul, Korea. CCRT [45 Gy over 5 weeks with 5-fluorouracil (5-FU) as HAIC] was followed by HAIC (5-FU/cisplatin combination every 4 weeks for 3-12 months), adjusted for tumor response. Down-staging succeeded in all eight patients, leaving no viable tumor thrombi in major vessels, although three patients first underwent hepatic resections. Due to deteriorating liver function, transplantation was the sole therapeutic option and offered a chance for cure. The 1-year disease-free survival rate was 87.5%. There were three instances of post-transplantation tumor recurrence during follow-up monitoring (median, 17 months; range, 10-22 months), but no deaths occurred. Median survival time from initial diagnosis was 33 months. Four postoperative complications recorded in three patients (anastomotic strictures: portal vein, 2; bile duct, 2) were resolved through radiologic interventions. Using an intensive tumor down-staging protocol of CCRT followed by HAIC, LDLT may be a therapeutic option for selected patients with locally advanced HCC and portal vein tumor thrombosis.
Adult ; Carcinoma, Hepatocellular/complications/drug therapy/surgery/*therapy ; *Chemoradiotherapy ; Cisplatin/therapeutic use ; Disease-Free Survival ; Female ; Fluorouracil/therapeutic use ; Humans ; Liver Neoplasms/complications/drug therapy/surgery/*therapy ; *Liver Transplantation ; *Living Donors ; Male ; Middle Aged ; Neoplasm Recurrence, Local ; *Portal Vein ; Venous Thrombosis/*complications

BACKGROUND/AIMS: Treating hepatocellular carcinoma (HCC) with portal vein tumor thrombosis (PVTT) remains controversial. We compared the outcomes of hepatic resection (HR), transarterial chemoembolization (TACE), and sorafenib therapy as treatments for HCC with PVTT. METHODS: Patients diagnosed as HCC with PVTT between January 2000 and December 2011 who received treatment with sorafenib, HR, or TACE were included. Patients with main PVTT, superior mesenteric vein tumor thrombosis, or Child-Turcotte-Pugh (CTP) class C were excluded. The records of 172 patients were analyzed retrospectively. HR, TACE, and sorafenib treatment were performed is 40, 80, and 52 patients respectively. PVTT was classified as either involving the segmental branch (type I) or extending to involve the right or left portal vein (type II). RESULTS: The median survival time was significantly longer in the HR group (19.9 months) than in the TACE and sorafenib groups (6.6 and 6.2 months, respectively; both p<0.001), and did not differ significantly between the latter two groups (p=0.698). Among patients with CTP class A, type I PVTT or unilobar-involved HCC, the median survival time was longer in the HR group than in the TACE and sorafenib groups (p=0.006). In univariate analyses, the initial treatment method, tumor size, PVTT type, involved lobe, CTP class, and presence of cirrhosis or ascites were correlated with overall survival. The significant prognostic factors for overall survival in Cox proportional-hazards regression analysis were initial treatment method (HR vs. TACE: hazard ratio=1.750, p=0.036; HR vs. sorafenib: hazard ratio=2.262, p=0.006), involved lobe (hazard ratio=1.705, p=0.008), PVTT type (hazard ratio=1.617, p=0.013), and CTP class (hazard ratio=1.712, p=0.012). CONCLUSIONS: Compared with TACE or sorafenib, HR may prolong the survival of patients with HCC in cases of CTP class A, type I PVTT or unilobar-involved HCC.
Adult ; Aged ; Antineoplastic Agents/*therapeutic use ; Carcinoma, Hepatocellular/complications/drug therapy/*therapy ; Chemoembolization, Therapeutic ; Combined Modality Therapy ; Female ; Follow-Up Studies ; Humans ; Liver Neoplasms/complications/drug therapy/*therapy ; Male ; Middle Aged ; Niacinamide/*analogs & derivatives/therapeutic use ; Phenylurea Compounds/*therapeutic use ; Portal Vein ; Proportional Hazards Models ; Retrospective Studies ; Severity of Illness Index ; Survival Rate ; Treatment Outcome ; Venous Thrombosis/*complications

Cirrhosis can occur with the development of portal vein thrombosis (PVT). PVT may aggravate portal hypertension, and it can lead to hepatic decompensation. The international guideline recommends for anticoagulation treatment to be maintained for at least 3 months in all patients with acute PVT. Low-molecular-weight-heparin and changing to warfarin is the usual anticoagulation treatment. However, warfarin therapy is problematic due to a narrow therapeutic window and the requirement for frequent dose adjustment, which has prompted the development of novel oral anticoagulants for overcoming these problems. We report a 63-year-old female who experienced complete resolution of recurrent acute PVT in liver cirrhosis after treatment with rivaroxaban.
Administration, Oral ; Factor Xa Inhibitors/*therapeutic use ; Female ; Humans ; Liver Cirrhosis/*complications/diagnosis ; Middle Aged ; Portal Vein ; Recurrence ; Rivaroxaban/*therapeutic use ; Tomography, X-Ray Computed ; Venous Thrombosis/complications/diagnostic imaging/*drug therapy

BACKGROUND: Currently, the hypertension (HTN) patients undergo appropriate medical treatment, and traditional risk factors are highly controlled. Therefore, potential risk factors of atherosclerotic vascular diseases (AVD) and venous thromboembolisms (VTE) in HTN should be reconsidered. We investigated thrombophilic genetic mutations and existing biomarkers for AVD or VTE in HTN patients receiving treatment. METHODS: A total of 183 patients were enrolled: AVD with HTN (group A, n=45), VTE with HTN (group B, n=62), and HTN patients without any vascular diseases (group C, n=76). The lipid profile, homocysteine (Hcy) levels, D-dimers, fibrinogen, antithrombin, lupus anticoagulant, and anti-cardiolipin antibody (aCL) were evaluated. Prothrombin G20210A, Factor V G1691A, and methylenetetrahydrofolate reductase (MTHFR) C677T and A1298C were analyzed. RESULTS: All patients revealed wild type prothrombin G20210A and Factor V G1691A polymorphisms. The frequency of MTHFR polymorphisms was 677CT (n=84, 45.9%); 677TT (n=46, 25.1%); 1298AC (n=46, 25.1%); and 1298CC (n=2, 1.1%). The MTHFR 677TT genotype tended to increase the odds ratio (OR) to AVD events in HTN patients (OR 2.648, confidence interval 0.982-7.143, P=0.05). The group A demonstrated significantly higher Hcy levels (P=0.009), fibrinogen (P=0.004), and platelet counts (P=0.04) than group C. Group B had significantly higher levels of D-dimers (P=0.0001), platelet count (P=0.0002), and aCL (P=0.02) frequency than group C. CONCLUSIONS: The MTHFR 677TT genotype and Hcy level could be potential risk factors associated with development of AVD in HTN patients receiving treatment. D-dimer and aCL might be useful to estimate the occurrence of VTE in them.
Adult ; Aged ; Antihypertensive Agents/therapeutic use ; DNA/analysis ; Factor V/genetics ; Female ; Fibrin Fibrinogen Degradation Products/analysis ; Genotype ; Homocysteine/blood ; Humans ; Hypertension/*complications/drug therapy ; Lipids/blood ; Male ; Methylenetetrahydrofolate Reductase (NADPH2)/genetics ; Middle Aged ; Odds Ratio ; Platelet Count ; Polymorphism, Single Nucleotide ; Prothrombin/genetics ; Real-Time Polymerase Chain Reaction ; Republic of Korea ; Risk Factors ; Vascular Diseases/*etiology/genetics ; Venous Thrombosis/*etiology/genetics

Portal vein thrombosis is an uncommon but an important cause of portal hypertension. The most common etiological factors of portal vein thrombosis are liver cirrhosis and malignancy. Albeit rare, portal vein thrombosis can also occur in the presence of local infection and inflammation such as pancreatitis or cholecystitis. A 52-year-old male was admitted because of general weakness and poor oral intake. He had an operation for colon cancer 18 months ago. However, colonic stent had to be inserted afterwards because stricture developed at anastomosis site. Computed tomography taken at admission revealed portal vein thrombosis and inflammation at colonic stent insertion site. Blood culture was positive for Escherichia coli. After antibiotic therapy, portal vein thrombosis resolved. Herein, we report a case of portal vein thrombosis with sepsis caused by inflammation at colonic stent insertion site which was successfully treated with antibiotics.
Anti-Bacterial Agents/therapeutic use ; Cholecystitis/etiology ; Colonic Neoplasms/pathology/therapy ; Escherichia coli/isolation & purification ; Escherichia coli Infections/drug therapy/etiology ; Humans ; Inflammation/*etiology ; Liver/diagnostic imaging ; Male ; Middle Aged ; Pancreatitis/etiology ; Portal Vein ; Sepsis/*diagnosis/drug therapy/microbiology ; Sigmoidoscopy ; Stents/*adverse effects ; Tomography, X-Ray Computed ; Venous Thrombosis/complications/*diagnosis

PURPOSETo compare the effects and side-effects of fondaparinux sodium and low molecular weight heparin in patients with hypercoagulability accompanied with traumatic infection.

METHODSThirty-six patients with post-traumatic infections in our hospital intensive care center were diagnosed with hypercoagulability from February 2012 to February 2013. These patients were randomly divided into 2 groups. In group F (18 patients), the patients were treated with fondaparinux sodium, 2.5 mg, 1/d for 11 d. In group L (18 patients), the patients were treated with low molecular weight heparin, 4100 U, 1/12 h for 11 d. The incidence of deep vein thrombosis, bleeding events and multiple organ dysfunction syndrome (MODS) and mortality of two groups after anticoagulation therapy were analyzed. Fibrinogen, D-dimer level and activity of antithrombin III were measured by the coagulation analyzer.

RESULTSThe incidence of deep vein thrombosis, MODS incidence and mortality were not significantly different between the two groups. The rate of bleeding evens in group F was lower than group L (p < 0.05). Antithrombin III got an upward trend after anticoagulant therapy, in which it was higher in group F than in group L on the 5th d and 11th d (p<0.05). Fibrinogen levels were gradually increased, and there was no significant difference between two groups (p>0.05). D-dimer was significantly decreased after anticoagulant therapy for 5 d (p<0.01), and there were significant differences between two groups on the 5th d and 7th d (p<0.05). It showed no significant difference on the 11th d (p>0.05).

CONCLUSIONFondaparinux sodium and low molecular weight heparin can effectively improve coagulopathy in patients with traumatic infection. Compared with low molecular weight heparin, fondaparinux sodium may reduce the risk of bleeding events in patients with hypercoagulability accompanied by traumatic infection.

Adult ; Aged ; Female ; Fibrin Fibrinogen Degradation Products ; analysis ; Heparin, Low-Molecular-Weight ; therapeutic use ; Humans ; Infection ; complications ; Male ; Middle Aged ; Multiple Organ Failure ; epidemiology ; Polysaccharides ; therapeutic use ; Thrombophilia ; drug therapy ; Venous Thrombosis ; epidemiology ; Wounds and Injuries ; complications

BACKGROUND/AIMS: Portal-vein thrombosis (PVT) develops in 10-25% of cirrhotic patients and may aggravate portal hypertension. There are few data regarding the effects of anticoagulation on nonmalignant PVT in liver cirrhosis. The aim of this study was to elucidate the safety, efficacy, and predictors of response to anticoagulation therapy in cirrhotic patients. METHODS: Patients with liver cirrhosis and nonmalignant PVT were identified by a hospital electronic medical record system (called BESTCARE). Patients with malignant PVT, Budd-Chiari syndrome, underlying primary hematologic disorders, or preexisting extrahepatic thrombosis were excluded from the analysis. Patients were divided into two groups (treatment and nontreatment), and propensity score matching analysis was performed to identify control patients. The sizes of the thrombus and spleen were evaluated using multidetector computed tomography. RESULTS: Twenty-eight patients were enrolled in this study between 2003 and 2014: 14 patients who received warfarin for nonmalignant PVT and 14 patients who received no anticoagulation. After 112 days of treatment, 11 patients exhibited significantly higher response rates (complete in 6 and partial in 5) compared to the control patients, with decreases in thrombus size of >30%. Compared to nonresponders, the 11 responders were older, and had a thinner spleen and fewer episodes of previous endoscopic variceal ligations, whereas pretreatment liver function and changes in prothrombin time after anticoagulation did not differ significantly between the two groups. Two patients died after warfarin therapy, but the causes of death were not related to anticoagulation. CONCLUSIONS: Warfarin can be safely administered to cirrhotic patients with nonmalignant PVT. The presence of preexisting portal hypertension is a predictor of nonresponse to anticoagulation.
Aged ; Anticoagulants/*therapeutic use ; Female ; Humans ; Liver Cirrhosis/complications/*diagnosis ; Male ; Middle Aged ; Portal Vein ; Propensity Score ; Severity of Illness Index ; Tomography, X-Ray Computed ; Venous Thrombosis/complications/*drug therapy/pathology ; Warfarin/therapeutic use

Protein S (PS), a vitamin K-dependent glycoprotein, performs an important role in the anticoagulation cascade as a cofactor of protein C. Because of the presence of a pseudogene and two different forms of PS in the plasma, protein S deficiency (PSD) is one of the most difficult thrombophilias to study and a rare blood disorder associated with an increased risk of thrombosis. We describe a unusual case of previously healthy 37-year-old man diagnosed with portal-splenic-mesenteric vein thrombosis secondary to PSD. The patient was admitted to the hospital due to continuous nonspecific abdominal pain and nausea. Abdominal computed tomography revealed acute venous thrombosis from inferior mesenteric vein to left portal vein via splenic vein, and laboratory test revealed decreased PS antigen level and PS functional activity. Conventional polymerase chain reaction and direct DNA sequencing analysis of the PROS1 gene demonstrated duplication of the 166th base in exon 2 resulting in frame-shift mutation (p.Arg56Lysfs*10) which is the first description of the new PROS1 gene mutation to our knowledge. Results from other studies suggest that the inherited PSD due to a PROS1 gene mutation may cause venous thrombosis in a healthy young man without any known predisposing factor.
Adult ; Anticoagulants/therapeutic use ; Base Sequence ; Blood Proteins/*genetics ; Codon, Terminator ; Exons ; Humans ; Male ; Mesenteric Veins/radiography ; Polymorphism, Restriction Fragment Length ; Portal Vein/radiography ; Protein S Deficiency/complications/*diagnosis ; Sequence Analysis, DNA ; Splenic Vein/radiography ; Tomography, X-Ray Computed ; Venous Thrombosis/*diagnosis/drug therapy/etiology

Adult ; Humans ; Intracranial Thrombosis ; diagnosis ; drug therapy ; etiology ; Male ; Methylprednisolone ; therapeutic use ; Nephrotic Syndrome ; complications ; drug therapy ; Venous Thrombosis ; diagnosis ; drug therapy ; etiology

No abstract available.
Acute Disease ; Anti-Bacterial Agents/therapeutic use ; Anticoagulants/therapeutic use ; Brucellosis/*complications/diagnosis/drug therapy/microbiology/transmission ; Humans ; Male ; Middle Aged ; Thrombophlebitis/etiology ; Treatment Outcome ; Venous Thrombosis/diagnosis/drug therapy/*etiology