We have evaluated the clinical outcomes of patients after transarterial chemoembolization (TACE) and 3-dimensional conformal radiotherapy for hepatocellular carcinoma (HCC) with portal vein tumor ...thrombosis (PVTT).
A registry database of 412 patients treated with TACE and three-dimensional conformal radiotherapy for HCC with PVTT between August 2002 and August 2008 were analyzed retrospectively. The radiotherapy volume included the PVTT, with a 2- to 3-cm margin to cover adjacent HCC. Intrahepatic primary HCC was managed by TACE before or after radiotherapy.
Median patient age was 52 years old, and 88.1% of patients were male. Main or bilateral PVTT was observed in 200 (48.5%) patients. Median radiation dose was 40 Gy (range, 21-60 Gy) delivered in 2- to 5-Gy fractions. We found that 3.6% of patients achieved a complete response and that 24.3% of patients achieved a partial response. The response and progression-free rates of PVTT were 39.6% and 85.6%, respectively. Median patient survival was 10.6 months, and the 1- and 2-year survival rates were 42.5% and 22.8%, respectively. Significant independent variables associated with overall survival included advanced tumor stage, alpha-fetoprotein level, degree of PVTT, and response to radiotherapy. Forty-one patients (10.0%) showed grade 3-4 hepatic toxicity during or 3 months after completion of radiotherapy. Grades 2-3 gastroduodenal complications were observed in 15 patients (3.6%).
Radiotherapy is a safe and effective treatment for PVTT in patients with HCC. These results suggested that the combination of TACE and radiotherapy is a treatment option for relieving and/or stabilizing PVTT in patients with advanced HCC.
Background & Aims
As surrogate markers for autoimmune hepatitis (AIH), serum alanine aminotransferase (ALT) and immunoglobulin G (IgG) are convenient to measure under immunosuppression. However, the ...long‐term prognosis of patients who achieve complete biochemical remission (CBR) in comparison with patients who achieve only biochemical remission (BR) is uncertain.
Methods
A total of 291 patients (89.7% female) diagnosed with AIH were retrospectively reviewed. CBR was defined as normal ALT and IgG levels with immunosuppression, while BR was defined as normal ALT levels. CBR was further divided into early CBR (<1year) and late CBR (≥1year) by the timing of remission. Liver‐related adverse outcomes including liver‐related death, liver transplantation and hepatocellular carcinoma were evaluated.
Results
With immunosuppressive treatment, 222 (76.3%) patients achieved CBR (early CBR: 168 and late CBR: 54). BR was achieved in 55 (18.9%) patients and 14 (4.8%) patients remained non‐remission. With a median follow‐up duration of 6.6 years, the risk of liver‐related mortality was the lowest in patients with CBR, followed by patients with late CBR, BR and non‐response. The cumulative risk of liver‐related adverse outcomes was the highest in patients with non‐response (8.51/100 person‐years PYs), followed by BR (1.95/100 PYs), late CBR (1.89/100 PYs) and early CBR (0.75/100 PYs). By multivariable analysis, age, cirrhosis and treatment responses were independently associated with liver‐related adverse outcomes.
Conclusions
Patients with CBR within 1 year after treatment initiation had the lowest risk of liver‐related adverse outcomes. Patients with late CBR and those with only BR had a comparable risk of long‐term outcomes.
Even with early stage hepatocellular carcinoma (HCC), patients are often ineligible for surgical resection, transplantation, or local ablation due to advanced cirrhosis, donor shortage, or difficult ...location. Stereotactic body radiation therapy (SBRT) has been established as a standard treatment option for patients with stage I lung cancer, who are not eligible for surgery, and may be a promising alternative treatment for patients with small HCC who are not eligible for curative treatment.
A registry database of 93 patients who were treated with SBRT for HCC between 2007 and 2009 was analyzed. A dose of 10-20 Gy per fraction was given over 3-4 consecutive days, resulting in a total dose of 30-60 Gy. The tumor response was determined using dynamic computed tomography or magnetic resonance imaging, which was performed 3 months after completion of SBRT.
The median follow-up period was 25.6 months. Median size of tumors was 2 cm (range: 1-6 cm). Overall patients' survival rates at 1 and 3 years were 86.0% and 53.8%, respectively. Complete and partial tumor response were achieved in 15.5% and 45.7% of patients, respectively. Local recurrence-free survival rate was 92.1% at 3 years. Most local failures were found in patients with HCCs > 3 cm, and local control rate at 3 years was 76.3% in patients with HCC > 3 cm, 93.3% in patients with tumors between 2.1-3 cm, and 100% in patients with tumors ≤ 2 cm, respectively. Out-of-field intrahepatic recurrence-free survival rates at 1 and 3 years were 51.9% and 32.4%, respectively. Grade ≥ 3 hepatic toxicity was observed in 6 (6.5%).
SBRT was effective in local control of small HCC. SBRT may be a promising alternative treatment for patients with small HCC which is unsuitable for other curative therapy.
In clinical practice, transarterial chemoembolization (TACE) has been widely used for the treatment of hepatocellular carcinoma (HCC) beyond as well as within guideline recommendations. Here we aimed ...to verify whether two consecutive non-responses could be an optimal criterion for creating a rule to stop TACE being performed on these patients.
This study evaluated 200 patients with HCC beyond the Milan criteria, initially treated with TACE. TACE response was determined using the mRECIST criteria via dynamic CT or MRI. Median follow-up duration was 23.9 months.
Within the 200 patients analyzed, 183 (91.5%) were male, with a total median age of 59.8 years. The mean size of the largest tumor was 6.8 cm, with 80 (40.0%) patients with ≥4 tumors. After the first TACE procedure, complete response, partial response, stable disease, or progressive disease were observed in 48 (24.0%), 87 (43.5%), 59 (29.5%) and 6 (3.0%) of patients, respectively. 45 (22.5%) patients showed no objective response (OR) following two consecutive TACE sessions. Of these, 28 received a subsequent TACE, with a 10.7% OR rate. Patients without OR showed poorer survival when compared to patients who achieved OR after repeated TACE. Multivariable analysis showed that size of the largest tumor >5cm and high alpha-fetoprotein of >200 ng/mL were significant factors associated with failure of OR to two consecutive TACE sessions.
Patients showing no OR to two consecutive TACE sessions will present a poor OR to subsequent TACE procedures. Early transition to systemic therapy may be advocated in such cases.
Background & Aims The effect of entecavir (ETV) therapy on viral suppression and hepatic function in hepatitis B virus (HBV) patients with decompensated cirrhosis has not been established. We ...evaluated ETV as first-line monotherapy in these patients. Methods We consecutively enrolled 70 HBV-infected patients with decompensated cirrhosis primarily treated with 0.5 mg/day ETV, and evaluated the clinical outcomes by intention-to-treat analyses. We also compared the virological responses of 55 patients treated for ⩾12 months (decompensated group) with those of 144 chronic hepatitis or compensated cirrhosis patients (compensated group). Results The cumulative transplantation-free survival was 87.1% at 1 year. ETV treatment for 12 months resulted in improved Child–Turcotte–Pugh (CTP) and model for end-stage liver disease (MELD) scores. Sixty-six percent (36/55) of patients achieved CTP class A and 49% (27/55) showed improvement in the CTP score of ⩾2 points after 12 months of ETV. The 1-year cumulative rates of HBV DNA negativity and HBeAg loss were 92.3% and 54.0%, respectively, by intention-to-treat analysis. The rates of HBV DNA negativity, HBeAg seroconversion/loss and ALT normalization at month 12 were similar for the decompensated and compensated groups. Cox regression analysis showed that pretreatment HBeAg seropositivity was a negative predictor of HBV DNA clearance during ETV therapy (hazard ratio, 0.514; 95% confidence interval 0.367–0.719; p < 0.001). Conclusions One-year initial ETV therapy was similarly effective in both compensated and decompensated liver disease HBV patients. In addition, it improved underlying liver function in decompensated patients.
We hypothesized that portal vein tumor thrombosis (PVTT) in hepatocellular carcinoma (HCC) increases portal pressure and causes esophageal varices and variceal bleedings. We examined the incidence of ...high-risk varices and variceal bleeding and determined the indications for variceal screening and prophylaxis.
This study included 1709 asymptomatic patients without any prior history of variceal hemorrhage or endoscopic prophylaxis who underwent upper endoscopy within 30 days before or after initial anti-HCC treatment. Of these patients, 206 had PVTT, and after 1:2 individual matching, 161 of them were matched with 309 patients without PVTT. High-risk varices were defined as large/medium varices or small varices with red-color signs and variceal bleeding. Bleeding rates from the varices were compared between matched pairs. Risk factors for variceal bleeding in the entire set of patients with PVTT were also explored.
In the matched-pair analysis, the proportion of high-risk varices at screening (23.0% vs. 13.3%; P = 0.003) and the cumulative rate of variceal bleeding (4.5% vs. 0.4% at 1 year; P = 0.009) were significantly greater in the PVTT group. Prolonged prothrombin time, lower platelet count, presence of extrahepatic metastasis, and Vp4 PVTT were independent risk factors related to high-risk varices in the total set of 206 patients with PVTT (Adjusted odds ratios 95% CIs, 1.662 1.151-2.401; 0.985 0.978-0.993; 4.240 1.783-10.084; and 3.345 1.457-7.680, respectively; Ps < 0.05). During a median follow-up of 43.2 months, 10 patients with PVTT experienced variceal bleeding episodes, 9 of whom (90%) had high-risk varices. Presence of high-risk varices and sorafenib use for HCC treatment were significant predictors of variceal bleeding in the complete set of patients with PVTT (Adjusted hazard ratios 95% CIs, 26.432 3.230-216.289; and 5.676 1.273-25.300, respectively; Ps < 0.05).
PVTT in HCC appears to increase the likelihood of high-risk varices and variceal bleeding. In HCC patients with PVTT, endoscopic prevention could be considered, at least in high-risk variceal carriers taking sorafenib.
Prior epidemiological evidences suggest that hepatitis B virus (HBV) infection is linked to cancers other than hepatocellular carcinoma. This prospective hospital registry-based case-control study ...aimed to investigate the sero-epidemiological association between chronic HBV infection and various types of cancer.
95,034 patients with first-diagnosed non-hepatocellular malignancy in a tertiary hospital between 2007 and 2014; and 118,891 non-cancer individuals as controls from a health promotion center were included. Cases and controls were compared for HBV surface antigen (HBsAg) positivity by conditional regression with adjustment for age, hypertension, diabetes, body mass index, alcohol consumption, smoking status and cholesterol level in both genders.
An analysis of matched data indicated significant associations of HBV infection with lymphoma (adjusted odds ratioAOR 1.53 95% CI 1.12-2.09 in men and 3.04 1.92-4.82 in women) and biliary cancer (2.591.98-3.39 in men and 1.711.16-2.51 in women). Cervical (1.491.11-2.00), uterine (1.691.09-2.61), breast (1.161.02-1.32), thyroid (1.491.28-1.74), and lung cancers (1.791.32-2.44) in women; and skin cancer (5.331.55-18.30) in men were also significantly related to HBV infection.
Chronic HBV infection is associated with several malignant disorders including lymphoma, and biliary, cervical, uterine, breast, thyroid, lung, and skin cancers. Our findings may offer additional insights into the development of these neoplasms and may suggest the need to consider HBV screening in cancer patients and cancer surveillance in HBV-infected subjects.
Combined hepatocellular-cholangiocarcinoma (cHCC-CC) can present as a hypervascular or peripherally enhancing tumor in dynamic imaging. We evaluated the effect of transarterial chemoembolization ...(TACE) on prognosis according to post-operative recurrence imaging patterns.
We retrospectively analyzed 42 cHCC-CC and 59 hepatocellular carcinoma (HCC-control) patients at the Asan Medical Center. We classified recurrent cHCC-CC according to enhancement pattern (globally enhancing: GE cHCC-CC, peripherally enhancing: PE cHCC-CC) and evaluated tumor response, time-to-local progression (TTPlocal), and overall survival (OS).
The GE cHCC-CC group had a significantly higher best objective response rate (complete remission + partial response) than the PE cHCC-CC group (36% vs 0%, P = 0.005), and it was comparable to that of the HCC-control group (35.6%, P = 0.97). TTPlocal in the GE cHCC-CC group was significantly shorter than in the HCC-control group (6.6 vs 27.1 months, P < 0.001), and was not significantly different from that in the PE cHCC-CC group (5.3 months, P = 0.12). OS was 12.4 months, 52.8 months, and 67.5 months in the PE cHCC-CC, GE cHCC-CC, and HCC-control groups, respectively (Ps < 0.05). The adjusted hazard ratios (HRs) for TTPlocal and OS revealed an independent association with enhancement pattern of recurrent cHCC-CC (TTPlocal: HR 2.46; 95% CI 1.10-5.46; P = 0.03; OS: HR 5.97; 95% CI 2.38-14.96; P < 0.001).
The GE cHCC-CC group showed better response and prognosis after TACE than the PE cHCC-CC group, but poorer response and prognosis than the HCC-control group. Enhancement patterns at recurrence were crucially associated with tumor response and overall survival.
The incidence of hepatocellular carcinoma (HCC) has been increasing among the elderly populations. Trans-arterial chemoembolization (TACE), a widely used first-line non-curative therapy for HCCs is ...an issue in geriatrics. We investigated the prognosis of elderly HCC patients treated with TACE and determined the factors that affect the overall survival.
We included 266 patients who were older than 65 years and had received TACE as initial treatment for HCC. We analyzed the skeletal muscle index (SMI) and visceral-to-subcutaneous fat ratio (VSR) around the third lumbar vertebrae using computed tomography scans. Muscle depletion with visceral adiposity (MDVA) was defined by falling below the median SMI and above the median VSR value sex-specifically. We evaluated the overall survival in association with MDVA and other clinical factors.
The mean age was 69.9 ± 4.5 years, and 70.3% of the patients were men. According to the Barcelona Clinic Liver Cancer (BCLC) staging system, 29, 136, and 101 patients were classified as BCLC 0, A, and B stages, respectively, and 79 (29.7%) had MDVA. During the median follow-up of 4.1 years, patients with MDVA had a shorter life expectancy than those without MDVA (P = 0.007) even though MDVA group had a higher objective response rate after the first TACE (82.3% vs. 75.9%, P = 0.035). Multivariate analysis revealed that MDVA (Hazard ratio HR 1.515) age (HR 1.057), liver function (HR 1.078), tumor size (HR 1.083), serum albumin level (HR 0.523), platelet count (HR 0.996), tumor stage (stage A, HR 1.711; stage B, HR 2.003), and treatment response after the first TACE treatment (HR 0.680) were associated with overall survival.
MDVA is a critical prognostic factor for predicting survival in the elderly patients with HCC who have undergone TACE.
Background/Aims The aim of the study was to evaluate the prevalence and risk factors of biopsy-proven non-alcoholic fatty liver disease (NAFLD) in potential living liver donors and to evaluate the ...efficacy of imaging techniques for the detection of steatosis in donors. Methods We reviewed the results of liver biopsy, ultrasonography (USG) and computed tomography (CT) and biochemical data performed in 589 consecutive potential liver donors as a pretransplantation work up from July 2004 to September 2005 at Asan Medical Centre. Results Of 589 participants, 408 (69.3%) were men, with a mean age of 31.1 ± 9.5 years. NAFLD (⩾5% steatosis in biopsy) was diagnosed in 303 (51.4%); >30% steatosis in 61 (10.4%) and non-alcoholic steatohepatitis in 13 (2.2%). The independent risk factors for >30% steatosis were age over 30 (OR = 2.223; p = 0.014), obesity (OR = 5.320; p < 0.001) and hypertriglyceridemia (OR = 2.253; p = 0.019) by multivariate analysis. The sensitivity of USG and CT for detecting >30% steatosis was 92.3% and 64.1%, and positive predictive value was only 34.5% and 45.1%, respectively. Conclusions NAFLD was highly prevalent in potential living liver donors. The independent risk factors for significant steatosis were older age, obesity and hypertriglyceridemia. USG and CT had limitations in detecting significant steatosis in liver donors.
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