Initial clinical experience with durvalumab plus tremelimumab in patients with unresectable hepatocellular carcinoma in real­world practice.

Although durvalumab plus tremelimumab (Dur/Tre) has been approved as first-line therapy for patients with unresectable hepatocellular carcinoma (u-HCC), its outcomes in real-world clinical practice are unclear. The present study aimed to evaluate the efficacy and safety of Dur/Tre treatment. This multicenter study was conducted between March 2023 and January 2024, and included 120 patients with u-HCC treated with Dur/Tre. Among the patients, 44 had no history of systemic treatment. Progression-free survival (PFS), therapeutic response and adverse events (AEs) were assessed. The objective response rate (ORR) and disease control rates (DCR) were 15.8 and 53.3%, respectively. The median PFS was 3.9 months. The incidence rates of AEs of any grade and those grade 3 or higher were 83.3 and 36.7%, respectively. Liver injury was the most frequent AE of any grade and grade 3 or higher. Although there was no significant difference in ORR and PFS between the first and later line groups (ORR 15.8 vs. 15.7%, P=0.986; PFS 4.5 vs. 3.6 months, P=0.213), there was a significant difference in DCR between the two groups (65.8 vs. 45.9%, P=0.034). No significant differences were noted between the first- and later-line treatment groups regarding the incidence rate of AEs. Decision tree analysis revealed that poor liver function and advanced age were significant variables for discontinuation owing to AEs. In conclusion, Dur/Tre as first-line therapy had better disease control responses compared with later-line therapy; however, this regimen should be carefully administered to patients with deteriorating hepatic function or advanced age.

Metabolic management after sustained virologic response in elderly patients with hepatitis C virus: A multicenter study.

AIMS: Hepatocellular carcinoma (HCC) develops even in patients with hepatitis C virus (HCV) eradication by direct-acting antiviral agents. Fatty liver and metabolic dysfunction are becoming major etiologies of HCC. We aimed to evaluate the impact of metabolic dysfunction-associated steatotic liver disease (MASLD), a new definition of steatotic liver disease, on the development of HCC after HCV eradication. METHODS: We enrolled 1280 elderly patients with HCV eradication and no history of HCC. We evaluated α-fetoprotein (AFP), Fibrosis-4 index and MASLD after 24 weeks of sustained virological response. Decision tree analysis was used to investigate factors associated with HCC development after HCV eradication. RESULTS: A total of 86 patients (6.7%) developed HCC during the follow-up period (35.8 ± 23.7 months). On multivariate analysis, serum AFP level (HR 1.08, CI 1.04-1.11, P = 0.0008), Fibrosis-4 index (HR 1.17, CI 1.08-1.26, P = 0.0007), and MASLD (HR 3.04, CI 1.40-6.58, P = 0.0125) at 24 weeks of sustained virological response were independent factors associated with HCC development. In decision tree analysis, the initial classifier for HCC development was AFP ≥7 ng/mL. However, in patients with AFP <7 ng/mL, MASLD, rather than Fibrosis-4 index, was the classifier for HCC development. No significant difference was observed in the cumulative incidence of HCC between patients with AFP ≥7 ng/mL and patients with AFP <7 ng/mL and MASLD. CONCLUSION: MASLD at 24 weeks of sustained virological response is a risk factor for HCC development in elderly patients with HCV eradication. Additionally, decision tree analysis revealed that MASLD was associated with HCC development, even in patients with serum AFP levels <7 ng/mL.

The impact of curative conversion therapy aimed at a cancer-free state in patients with hepatocellular carcinoma treated with atezolizumab plus bevacizumab.

BACKGROUND AND AIMS: We aimed to validate the predictive factors for tumor response and the prognostic impact of conversion therapy aimed at cancer- and drug-free states in patients with unresectable hepatocellular carcinoma (u-HCC) undergoing atezolizumab plus bevacizumab (Atez/Bev) therapy. METHODS: This retrospective study enrolled 156 patients who were Child-Pugh class A with u-HCC treated using Atez/Beva. The profile of objective response was investigated using decision-tree analysis. Progression-free, recurrence-free, and overall survival were assessed. RESULTS: The progression-free and overall survival were 6.1 and 18.0 months, respectively. Objective response and disease control rates were 32.0% and 84.0%, respectively. Decision-tree analysis revealed that neutrophil-to-lymphocyte ratio (NLR) <3, modified albumin-bilirubin grade (m-ALBI) 1 or 2a, and age < 75 were sequential splitting variables for the objective response, respectively. In the multivariate analysis, NLR <3 and m-ALBI grade 1 or 2a were identified as predictive factors for objective response. We successfully achieved eligibility for conversion therapy in 17 patients after Atez/Bev therapy significant response. Following conversion therapy, the curative therapy group, including surgical resection or radiofrequency ablation (RFA), had significantly higher recurrence-free survival than did the transcatheter arterial chemoembolization (TACE) and Atez/Bev discontinuation (surgical resection or RFA; not reached vs. TACE; 5.3 months, p = 0.008, Atez/Bev discontinuation; 3.9 months, p = 0.048, respectively) groups. CONCLUSIONS: NLR <3 and m-ALBI grade 1 or 2a were predictive factors for conversion therapy, leading to cancer- and drug-free states in patients with u-HCC undergoing Atez/Bev therapy. Moreover, surgery or RFA may be suitable for conversion therapy for cancer-free status.

Deterioration of liver function and aging disturb sequential systemic therapy for unresectable hepatocellular carcinoma.

This study aimed to investigate the clinical characteristics of patients with unresectable hepatocellular carcinoma (HCC), who were eligible for sequential systemic therapy. We evaluated 365 patients with HCC who underwent systemic therapy after 2017. The overall survival (OS) was 13.7 months, 19.2 months, and 35.6 months in the first-line, second-line, and third-line or later therapy groups, respectively. Multivariate analysis revealed that the modified-albumin-bilirubin (m-ALBI) grade, macrovascular invasion, extrahepatic spread, discontinuation due to adverse events (AEs), and sequential therapy were independent factors for OS. At the end of each therapy, the ALBI score was significantly worse among patients with discontinuation due to AEs than among those without. The conversion rate to second-line and third-line therapy among patients with discontinuation due to AEs was significantly lower than that among patients without (30.4% vs. 69.2%, p < 0.001; 6.7% vs. 58.3%; p < 0.001, respectively). In the decision tree analysis, m-ALBI grade 1 or 2a and non-advanced age were selected splitting variables, respectively, for sequential systemic therapy. In conclusion, sequential therapy prolonged the OS of unresectable HCC. Additionally, good hepatic function and non-advanced age were clinically eligible characteristics for sequential systemic therapy.

Association between Adverse Events and Prognosis in Patients with Hepatocellular Carcinoma Treated with Atezolizumab Plus Bevacizumab: A Multicenter Retrospective Study.

This study aimed to evaluate the correlation between adverse events (AEs) and overall survival (OS) in patients with unresectable hepatocellular carcinoma treated with atezolizumab plus bevacizumab (atezo/beva). This was a multicenter study in which 130 patients were enrolled. Hypertension and skin disorders had a significant correlation with longer survival (median survival time (MST): not reached vs. 14.3 months and not reached vs. 14.8 months, p = 0.001 and p = 0.047, respectively). In contrast, liver injuries were significantly correlated with shorter survival (MST: 14.7 months vs. not reached, p = 0.036), and the median development time was 21 days. In a logistic regression analysis, fatigue ≥ grade 2, liver injury ≥ grade 3, and modified albumin-bilirubin grade 2b were identified as independent factors for discontinuation due to AEs. The OS in the no discontinuation due to AE group was significantly longer than that in the discontinuation due to AEs group (MST not reached vs. 11.2 months, p = 0.001). We concluded that the development of liver injury was a negative factor for OS and that we should be vigilant in monitoring AE during atezo/beva treatments.

Potential efficacy of hepatic arterial infusion chemotherapy using gemcitabine, cisplatin, and 5-fluorouracil for intrahepatic cholangiocarcinoma.

Intrahepatic cholangiocarcinoma (ICC) has a poor prognosis, as the resectability rate is low due to its diagnosis at a late/advanced stage. Moreover, most patients with resected ICC eventually relapse. Hepatic arterial infusion chemotherapy (HAIC) has been indicated only by a few reports to be effective in patients with advanced ICC; thus, its efficacy for these patients remains unclear. This study aimed to evaluate the efficacy of HAIC using gemcitabine, cisplatin, and 5-fluorouracil in patients with advanced ICC. A total of 18 patients who underwent HAIC were retrospectively investigated. The patients received gemcitabine, cisplatin, and 5-fluorouracil through one artery. In patients who received gemcitabine plus cisplatin (n = 10), the response and disease control rates were 0% and 80.0%, respectively; the median overall survival (OS) and progression-free survival (PFS) after treatment initiation were 6.3 and 3.7 months, respectively. In patients who never received chemotherapy (n = 8), the response and disease control rates were 37.5% and 75%, respectively; the median OS and PFS were 20.6 and 8.1 months, respectively. Moreover, we compared the patients who received HAIC using gemcitabine, cisplatin, and 5-fluorouracil to patients whose tumors were refractory to systemic gemcitabine and cisplatin therapy. The OS of the patients who received HAIC was better than that of the patients who received standard chemotherapy cohort since the gemcitabine plus cisplatin combination therapy-refractory response and disease onset (P = 0.045, 0.006). HAIC using gemcitabine, cisplatin, and 5-fluorouracil may be effective as a therapeutic option for patients with advanced ICC.

Efficacy and Safety of Arterial Infusion Chemotherapy in Patients with Advanced Hepatocellular Carcinoma and Child-Pugh Class B: A Retrospective Cohort Study.

INTRODUCTION: Although many treatment options are available for patients with advanced hepatocellular carcinoma (HCC) and Child-Pugh (CP) class A, those for patients with CP class B remain limited. We aimed to assess the safety and efficacy of hepatic arterial infusion chemotherapy (HAIC) using 5-fluorouracil and cisplatin in patients with advanced HCC and CP class B. METHODS: Sixty patients who received HAIC with 5-fluorouracil and cisplatin at Kurume Chuo Hospital between April 2012 and March 2021 were recruited. Cisplatin (30 mg administered over 2 h) and 5-fluorouracil (1,250 mg, 72-h constant infusion) were administered to the tumor-feeding artery every 2 weeks. The primary endpoint was overall survival (OS), while the secondary endpoints were progression-free survival and adverse effects. RESULTS: Among the 60 patients, CP class A and class B were noted in 30 patients each. OS did not significantly differ between the two classes. After 4 weeks of HAIC with 5-fluorouracil and cisplatin, 12 patients in the class B group exhibited improved CP scores (CPSs) relative to those at the start of treatment. There was a significant difference in OS between patients whose CPSs had improved and those whose scores remained unchanged or had worsened. CONCLUSIONS: HAIC using 5-fluorouracil and cisplatin is effective and safe for patients with CP class B, and improvements in CPSs after 4 weeks of this therapy may represent a predictive marker of treatment efficacy regardless of pretreatment CPS in patients with CP class B.

Feasibility and safety of a novel indwelling catheter system via the femoral artery for intermittent transarterial therapy for treating malignant liver tumors.

PURPOSE: An indwelling arterial access system via the brachial artery, System-i, has been previously reported. We have modified the technique for the femoral artery approach. This study aimed to evaluate the feasibility and safety of the modified System-i for patients with malignant liver tumors. MATERIALS AND METHODS: The modified System-i is an indwelling catheter that provides vascular access for inserting a microcatheter without repeated punctures to the femoral artery. Between 2018 and 2020, the system was implanted for 50 patients with malignant liver tumors. We used the system for patients with difficulty in inserting the conventional indwelling catheter system. To place the system, a side-holed catheter was implanted in the femoral artery, and the tip of the catheter was placed in the superficial femoral artery through the contralateral iliac artery. Using this system, transcatheter arterial chemoembolization or hepatic arterial infusion chemotherapy was performed. A shaped high-flow microcatheter and a non-tapered microcatheter were used with the system. The technical aspects and outcomes of the system were also assessed. RESULTS: Implantation of the system was successful in all patients. The median implantation time was 40 min. The main reason for implantation was obstruction or stenosis of the hepatic artery. Among the 50 patients, 11 (22%) showed complications, of which four had major complications/class C based on the SIR criteria. CONCLUSION: The modified System-i is a safe system that can be a feasible repeated interventional radiological treatment via the femoral approach. We need to evaluate the efficacy of this system in the treatment of advanced cancers in the future. The modified System-i is a novel indwelling catheter system that allows vascular access to perform intermittent transarterial therapy, such as transcatheter arterial chemoembolization and hepatic arterial infusion chemotherapy via the femoral approach. In this study, we report the technical details and safety of the system.

First-line sorafenib sequential therapy and liver disease etiology for unresectable hepatocellular carcinoma using inverse probability weighting: A multicenter retrospective study.

BACKGROUND AND AIMS: Sequential therapy with molecular-targeted agents (MTAs) is considered effective for unresectable hepatocellular carcinoma (HCC) patients. This study purposed to evaluate the efficacy of sequential therapy with sorafenib (SORA) as a first-line therapy and to investigate the therapeutic impact of SORA in nonalcoholic fatty liver disease (NAFLD) or nonalcoholic steato hepatitis (NASH)-related HCC. METHODS: We evaluated 504 HCC patients treated with SORA (Study-1). The times of administration for sorafenib from 2009 to 2015, 2016 to 2017, and 2018 and later were defined as the early-, mid-, and late-term periods, respectively. Among them, 180 HCC patients treated with SORA in addition to MTAs in the mid- and late-term periods were divided into groups based on disease etiology (NAFLD or NASH [n = 37] and viral or alcohol [n = 143]), and outcomes were compared after inverse probability weighting (IPW) (Study-2). RESULTS: Overall survival (OS) of HCC patients who received sequential MTA therapy after first-line SORA was significantly longer. The median survival times (MST) were 12.6 versus 17.6 versus 17.4 months in the early-term group, mid-term group, and the later-time group (early vs. mid, p = 0.014, early vs. later. p = 0.045), respectively. (Study-1). In Study-2, there was no significant differences in OS between the Virus/alcohol group and the NAFLD/NASH group in patients who received sequential therapy (MST was 23.4 and 27.0 months p = 0.173, respectively). The NAFLD or NASH, female sex, albumin-bilirubin (ALBI) grade 2b, and major Vp (Vp3/Vp4) were significant factors for OS treated with SORA. CONCLUSIONS: Sequential therapy with SORA as the first-line treatment improved the prognosis of unresectable HCC patients and was effective regardless of HCC etiology.

Initial Experience of Atezolizumab Plus Bevacizumab for Unresectable Hepatocellular Carcinoma in Real-World Clinical Practice.

BACKGROUND: Atezolizumab plus bevacizumab was approved for patients with hepatocellular carcinoma (HCC). Although clinical trials have revealed its efficacy, the outcomes in the real-world clinical practice are unclear. We retrospectively evaluated the efficacy and safety of atezolizumab plus bevacizumab for HCC. MATERIALS AND METHODS: This is a multicenter study conducted between November 2020 and March 2021. Among the 61 patients, 51 were assessed for progression-free survival (PFS), therapeutic response, and adverse events (AEs). RESULTS: The median PFS was 5.4 months. The objective response rate (ORR) was 35.3%. The disease control rate (DCR) was 86.3%. The incidence rates of AEs at any grade and grade >3 were 98.0% and 29.4%, respectively. The most frequent AE at any grade and grade >3 was hepatic disorder. In patients with a previous history of molecular targeted agent (MTA) or the degree of albumin-bilirubin (ALBI) grade, there were no significant differences in the PFS, ORR, DCR, and incidence rates of AEs. CONCLUSION: The study demonstrated that atezolizumab plus bevacizumab was effective and safe for patients with HCC even in the real-world setting including patients with a previous MTA history or other than ALBI grade 1.

Survival Benefit of Hepatic Arterial Infusion Chemotherapy over Sorafenib in the Treatment of Locally Progressed Hepatocellular Carcinoma.

BACKROUND: Not all patients with hepatocellular carcinoma (HCC) benefit from treatment with molecular targeted agents such as sorafenib. We investigated whether New-FP (fine-powder cisplatin and 5-fluorouracil), a hepatic arterial infusion chemotherapy regimen, is more favorable than sorafenib as an initial treatment for locally progressed HCC. METHODS: To avoid selection bias, we corrected the data from different facilities that did or did not perform New-FP therapy. In total, 1709 consecutive patients with HCC initially treated with New-FP or sorafenib; 1624 (New-FP, n = 644; sorafenib n = 980) were assessed. After propensity score matching (PSM), overall survival (OS) and prognostic factors were assessed (n = 344 each). Additionally, the patients were categorized into four groups: cohort-1 [(without macrovascular invasion (MVI) and extrahepatic spread (EHS)], cohort-2 (with MVI), cohort-3 (with EHS), and cohort-4 (with MVI and EHS) to clarify the efficacy of each treatment. RESULTS: New-FP prolonged OS than sorafenib after PSM (New-FP, 12 months; sorafenib, 7.9 months; p < 0.001). Sorafenib treatment, and severe MVI and EHS were poor prognostic factors. In the subgroup analyses, the OS was significantly longer the New-FP group in cohort-2. CONCLUSIONS: Local treatment using New-FP is a potentially superior initial treatment compared with sorafenib as a multidisciplinary treatment in locally progressed HCC without EHS.

Factors associated with advanced hepatic fibrosis in patients with various internal diseases: A multicenter community-based survey.

BACKGROUND AND AIMS: Advanced hepatic fibrosis can occur in patients with various diseases, including diabetes mellitus and hypertension. We aimed to investigate the prevalence and risk factors of advanced hepatic fibrosis in patients with various internal diseases. PATIENTS AND METHODS: We performed a community-based survey in which 1012 patients were enrolled (mean age, 63.1 ± 10.8 years; female/male, 505/507). Hepatic fibrosis was evaluated by Fib-4 index and patients were classified into high and low Fib-4 groups. Independent factors for the high Fib-4 group were analyzed using logistic regression and decision tree analysis. RESULTS: A high prevalence of high Fib-4 index was observed in patients with cardiovascular diseases; 37.1% of patients with hypertension belonged to the high Fib-4 group. Independent factors associated with the high Fib-4 group were BMI (OR 0.95, 95%CI 0.918-0.989, P < 0.01), male sex (OR 1.35, 95%CI 1.03-1.78, P < 0.05), and hypertension (OR 1.41, 95%CI 1.03-1.92, P < 0.05). In patients with hypertension, a decision tree algorithm revealed three profiles for Fib-4 index: 1) creatinine level < 0.76 mg/dL (high Fib-4; 30.0%), 2) creatinine level ≥ 0.76 mg/dL without sodium-glucose cotransporter 2 inhibitor (SGLT2i) treatment (high Fib-4; 48.2%), and 3) creatinine level ≥ 0.76 mg/dL with SGLT2i treatment (high Fib-4; 23.5%). CONCLUSIONS: A high prevalence of advanced hepatic fibrosis was observed in patients with hypertension. Hypertension was an independent risk factor, and creatinine level and SGLT2i were divergence variables for advanced hepatic fibrosis. Thus, hypertension with chronic kidney injury may exacerbate hepatic fibrosis, while SGLT2i treatment may ameliorate hepatic fibrosis.

Intermittent transcatheter therapy through a new indwelling catheter system for patients with hepatocellular carcinoma.

PURPOSE: This paper describes the technical details of the new indwelling catheter system, which we refer to as System-i, and provides an overview of our experience with this system at our institution. MATERIALS AND METHODS: The system is implanted via the left brachial artery. The feeding artery of the tumor is catheterized at each treatment, and the system can be used for multiple treatments via more than one feeding artery. Between January 2004 and January 2013, System-i was used to administer 398 treatments in 30 patients with hepatocellular carcinoma (HCC). The technical aspects and outcomes of treatment procedures were evaluated. RESULTS: Implantation was successful in all cases. System-i was used for a median number of 11 treatments per patient over a median period of 5.7 months, and 71.6 % of all treatments were administered on an outpatient basis. CONCLUSION: System-i provides an effective and safe method for selective catheterization of feeding arteries for administration of transcatheter arterial chemoembolization or infusion in patients with HCC. Treatment regimens can be individualized without limiting the number of treatments or treatment locations, and patients can be treated on an outpatient basis.

Significance of glucose intolerance and SHIP2 expression in hepatocellular carcinoma patients with HCV infection.

Glucose intolerance frequently is found in hepatocellular carcinoma (HCC) patients with hepatitis C virus (HCV) infection; however, the significance of glucose intolerance remains unclear. In addition, SH2 domain-containing inositol phosphatase (SHIP) 2 is a negative regulator of intracellular insulin signaling; however, changes in SHIP2 expression have not been investigated in HCC. To assess the significance of glucose intolerance, we analyzed 118 HCC patients with HCV infection. Twenty HCC specimens were used for immunoblotting and immunostaining for SHIP2. Patients were classified into two groups: a glucose intolerance group (n=39) and a normal glucose tolerance group (n=79). There was no significant difference in the disease-free survival (P=0.838) or long-term survival (P=0.091) between the groups. However, for males, the cumulative survival rate was significantly lower in the glucose intolerance group (n=22) than that in the normal glucose tolerance group (n=52) (P=0.036). In multivariate analysis, Child-Pugh class (P=0.0003) and glucose intolerance (P=0.036) were identified as statistically significant and independent prognostic factors in males. SHIP2 expression level decreased in HCC compared to that in nontumor tissues. In conclusion, this study is the first to demonstrate the significance of glucose intolerance in prognosis of male HCC patients and down-regulation of SHIP2 expression in HCC.

Hyperplastic nodular hepatic lesions following end-to-side portacaval shunting in childhood.

We describe a 48-year-old man with nodular intrahepatic lesions accompanied by communication between the inferior vena cava and portal systems as well as absence of intrahepatic portal veins. After infection with malaria in childhood, end-to-side portacaval shunting had been performed to treat upper gastrointestinal bleeding at the age of 15 years. A biopsy specimen obtained under ultrasonographic guidance showed hyperplastic nodules suggestive of focal nodular hyperplasia. The estradiol concentration in the blood was elevated (55 pg/ml). This case suggests that portacaval shunting may be associated with hyperplastic liver nodules through hyperestrogenemia and abnormal hepatic hemodynamics.

Temporary indwelling catheter system via the left brachial artery: evaluation in 83 patients with hepatic tumors.

OBJECTIVE: The purpose of our study was to evaluate retrospectively the usefulness and complications associated with a temporary indwelling catheter system through the brachial artery for patients with liver tumors. CONCLUSION: The temporary indwelling catheter system via the left brachial artery can be used not only for CO2-enhanced sonographically guided aspiration biopsy, radiofrequency ablation, and percutaneous ethanol injection, but also for short-term hepatic arterial infusion chemotherapy and transcatheter arterial chemoembolization.

Appearance-specific satiety increases appetite and quality of life in patients with metastatic liver tumor: a case report.

Loss of appetite is frequently seen and is a main factor affecting quality of life (QOL) in patients with advanced cancer. The etiology for loss of appetite in patients with cancer is multifactorial. The sensory properties of food are factors regulating appetite. Changes in taste, smell and texture of foods influence food intake. The appearance of the food is also a notable factor in sensory-specific satiety. We described a 46-year-old Japanese woman with multiple metastatic liver tumors. Although there was no obvious factor for loss of appetite, she suffered from a loss of appetite and subsequent malnutrition. In order to improve the appearance of food, we reduced the diet to 1,000 kcal/day from 1,500 kcal/day. On the new diet, the patient's appetite significantly increased and patient's nutritional status was improved. Eating whole diet was an important achievement and increased in mental aspects of QOL. Arrangement for the appearance of food may be a simple and nontoxic therapeutic strategy for patients with cancer suffering a loss of appetite.

Value of fusing PET plus CT images in hepatocellular carcinoma and combined hepatocellular and cholangiocarcinoma patients with extrahepatic metastases: preliminary findings.

BACKGROUND/AIMS: This study aimed to evaluate the usefulness of (18)F-fluoro-2-deoxy-d-glucose positron emission tomography (PET) and PET plus computed tomography (CT) fusion images for the detection of extrahepatic metastases of hepatocellular carcinoma (HCC) and combined hepatocellular and cholangiocarcinoma (combined HCC/CC). METHODS: Twenty-one patients with HCC and combined HCC/CC were enrolled in the study from December 2004 to February 2005. In all patients, PET and CT of the chest to pelvis region were performed. The sensitivity of PET plus CT fusion images was compared with the sensitivity of PET, CT, and bone scintigraphy. RESULTS: In 14 patients, a total of 58 extrahepatic metastases were diagnosed. The detection rate of PET plus CT fusion images, PET, CT, and bone scintigraphy was 98.2% (57 of 58 metastases), 89.6% (52 of 58 metastases), 91.2% (52 of 57 metastases), and 68.7% (11 of 16 bone metastases), respectively. No extrahepatic metastases were detected in the other seven patients. The detection rate of PET was 10/18 (55.6%) for intrahepatic lesions of HCC and combined HCC/CC. CONCLUSIONS: The fusion of PET plus CT images is useful in detecting extrahepatic metastases in HCC and combined HCC/CC patients.

The close relationship between heparanase and cyclooxygenase-2 expressions in signet-ring cell carcinoma of the stomach.

Signet-ring cell carcinoma (SRC) of the stomach exhibits diffuse growth and invasion without forming ducts. Destruction of the surrounding basal membrane and angiogenesis appear to be required for SRC to exhibit marked invasion and growth. We recently reported that heparanase (HPA) and cyclooxygenase-2 (COX-2) were strongly correlated with microvessel density, and that COX-2 expression is up-regulated by HPA in esophageal cancer. In this study, we examined the relationship between HPA expression and that of COX-2 in SRC of the stomach. We examined HPA and COX-2 expression in 3 cell lines derived from SRC of the stomach and in 50 SRC lesions of stomach by immunohistochemistry (IHC), in situ hybridization, and reverse transcriptase-polymerase chain reaction (RT-PCR). We also examined the relationships among HPA expression, COX-2 expression, and the clinicopathologic features of SRC, mean age, sex, invasion depth, regional lymph node metastasis, lymphatic invasion, and venous blood vessel invasion. Of the 3 cell lines, 2 exhibited both HPA and COX-2 mRNA expression on RT-PCR. Of the 3 cell lines, 1 exhibited only HPA mRNA expression on RT-PCR. Heparanase expression was confirmed in 23 (46%) of 50 tumor samples by IHC. COX-2 expression was confirmed in 25 (50%) of the 50 tumor samples by IHC. In situ hybridization revealed messenger RNA expression in the same area as in that revealed by IHC. A close correlation was noted between HPA and COX-2 expressions (P < .0001). The present study thus elucidated the biologic features of SRC of the stomach related to growth and angiogenesis.

Prophylactic lamivudine administration prevents exacerbation of liver damage in HBe antigen positive patients with hepatocellular carcinoma undergoing transhepatic arterial infusion chemotherapy.

BACKGROUND AND AIMS: Exacerbation of liver damage during transhepatic arterial infusion chemotherapy (THAIC) is a critical complication in patients with hepatitis B virus (HBV) related hepatocellular carcinoma (HCC). We previously reported that HBe antigen positivity was the associating factor for the exacerbation of liver damage. In the present study, we investigated the effect of lamivudine administration for exacerbation of liver damage in such patients. PATIENTS AND METHODS: Seventeen patients with HBV-related hepatocellular carcinoma who received THAIC were reviewed. Eight of these patients received lamivudine administration. Nine patients did not receive lamivudine administration. All patients were HBe antigen positive. Liver function tests, liver enzymes, HBV-DNA levels, HBe antigen, HBe antibody, and mutation in the precore and core-promoter regions of HBV DNA were evaluated. RESULTS: In the lamivudine-treated group, HBV-DNA levels were significantly reduced and did not increase throughout chemotherapy. Lamivudine did not induce any changes in precore or core-promoter regions. Although levels of alanine aminotransferase (ALT), asparate aminotransferase (AST), total bilirubin, and prothrombin time (PT) in the lamivudine-treated group did not change, levels of ALT, AST and total bilirubin increased, and PT were prolonged in the untreated group by chemotherapy. No patients receiving lamivudine administration showed exacerbation of liver damage. Exacerbation of liver damage was detected in six patients without lamivudine administration. Of these, three patients died of progressive liver failure due to reactivation of HBV. CONCLUSION: These results indicate that prophylactic lamivudine administration reduces HBV-DNA levels and prevents exacerbation of liver damage throughout the period of chemotherapy in HBe antigen positive patients with hepatocellular carcinoma.