Real-world efficacy of sofosbuvir plus velpatasvir therapy for patients with hepatitis C virus-related decompensated cirrhosis.

AIM: Combination therapy with sofosbuvir (SOF) plus velpatasvir (VEL) is approved for patients with hepatitis C virus (HCV)-related decompensated cirrhosis. We analyzed the real-world efficacy of SOF/VEL therapy. METHODS: Thirty-three patients with HCV-related decompensated cirrhosis (25 and eight patients with Child B and C, respectively) were treated with SOF/VEL for 12 weeks. The HCV non-structural protein (NS)5A and NS5B drug resistance-associated substitutions (RASs) were determined by direct sequencing. RESULT: Thirty-two of 33 patients completed the treatment, but the remaining patient discontinued the therapy during third week of the treatment due to aggravation of hepatic encephalopathy. Serum HCV-RNA became negative during the treatment in all patients but relapsed after the end of therapy in five patients. In total, 28 out of 33 patients (85%) achieved sustained virological response 12 weeks following completion of treatment (SVR12). The SVR12 rate was 96% in patients with Child B, but significantly lower, at 50%, in patients with Child C (P < 0.05). In genotype 1b HCV-infected patients, all eight patients without baseline NS5A RASs, but only three of seven patients with RASs, achieved SVR12. Multivariate analysis identified Child B (odds ratio, 35.8 for Child C; P = 0.045) as an independent predictor of SVR12. Median serum albumin levels significantly increased only in patients who achieved SVR12. Child-Pugh scores improved in 16 of 28 patients (57%) following achievement of SVR12. CONCLUSION: The effect of SOF/VEL therapy is lower for patients with Child C. Improvement of hepatic function is expected after viral eradication with SOF/VEL therapy in patients with decompensated cirrhosis.

Advanced liver fibrosis effects on the response to sofosbuvir-based antiviral therapies for chronic hepatitis C.

BACKGROUND: Sustained virological response (SVR) rates for the treatment of chronic hepatitis C virus (HCV)-infected patients have drastically improved with the use of direct-acting antiviral (DAA) therapies; however, a small minority of patients still fails to eradicate the virus. We analyzed factors associated with SVR in DAA therapy and the effect of age and liver fibrosis on treatment response. METHODS: Nine hundred and eighteen patients with chronic HCV infection were treated with 24 weeks of daclatasvir plus asunaprevir (DCV + ASV) or 12 weeks of sofosbuvir plus ledipasvir (SOF + LDV), ombitasvir, paritaprevir plus ritonavir (OMB + PTV + r) or sofosbuvir plus ribavirin (SOF + RBV). Multivariate logistic regression analysis was used to identify factors associated with SVR. The effect of age and liver fibrosis on SVR was analyzed. RESULTS: The overall SVR rate was 95.4% (876 of 918 patients), and rates by DAA regimen were 93.4%, 95.7%, 100%, and 95.0% in DCV + ASV-treated, SOF + LDV-treated, OMB + PTV + r-treated, and SOF + RBV-treated patients, respectively. Patients older than 75 years achieved a similar SVR rate with those aged 75 years or younger (96.4% and 94.8%, respectively). Multivariate logistic regression analysis identified absence of DAA therapy history (odds ratio [OR], 3.868 for presence; P = 0.002) and FIB-4 index of less than 3.25 (OR, 5.042 for ≥3.25; P = 0.001) as independent predictors for SVR. SVR rates were significantly lower in patients with FIB4 index of 3.25 or more compared with those with less than 3.25, especially in sofosbuvir-based therapies such as SOF + LDV-treated or SOF + RBV-treated patients. CONCLUSION: Both older and younger patients respond similarly to DAA therapy. Advanced liver fibrosis affects the virological response to sofosbuvir-based therapy.

Hepatic arterial infusion chemotherapy followed by sorafenib in patients with advanced hepatocellular carcinoma (HICS 55): an open label, non-comparative, phase II trial.

BACKGROUND: In patients with advanced hepatocellular carcinoma (HCC), evidence is unclear as to whether hepatic arterial infusion chemotherapy (HAIC) or sorafenib is superior. We performed a prospective, open-label, non-comparative phase II study to assess survival with HAIC or HAIC converted to sorafenib. METHODS: Fifty-five patients were prospectively enrolled. Patients received HAIC as a second course if they had complete response, partial response, or stable disease (SD) with an alpha fetoprotein (AFP) ratio < 1 or a des-γ-carboxy prothrombin (DCP) ratio < 1. Patients were switched to sorafenib if they had SD with an AFP ratio > 1 and a DCP ratio > 1 or disease progression. The primary endpoint was the 1-year survival rate. Secondary endpoints were the 2-year survival rate, HAIC response, survival rate among HAIC responders, progression-free survival, and adverse events. RESULTS: Of the 55 patients in the intent-to-treat population, the 1-year and 2-year survival rates were 64.0 and 48.3%, respectively. After the first course of HAIC, one (1.8%) patient showed complete response, 13 (23.6%) showed partial response, 30 (54.5%) had SD, and 10 (18.1%) patients had progressive disease. Twenty-three patients (41.8%) had SD with AFP ratios < 1 or DCP ratios < 1, and 7 (12.7%) had SD with AFP ratios > 1 and DCP ratios > 1. Thirty-seven patients (68.5%) were responders and 17 (30.9%) were non-responders to HAIC. In responders, the 1-year and 2-year survival rates were 78 and 62%, respectively. CONCLUSION: Given the results of this study, this protocol deserves consideration for patients with advanced HCC. This trial was registered prospectively from December 12. 2012 to September 1. 2016.

A trial of the use of patency capsules in combination with overnight capsule endoscopy.

BACKGROUND: The PillCam® patency capsule (PPC) was developed to minimize the risk of capsule retention during capsule endoscopy (CE). Typically, the use of patency capsules prior to CE requires patients to be monitored over a period of time. To reduce the need for frequent outpatient visits during PPC examination and CE, we developed the overnight CE (ON-CE) procedure. METHODS: Between October 2012 and January 2014, a total of 19 patients (15 males and 4 females, mean age 48.4 years) were administered PPC to assess the patency of the small intestine prior to ON-CE at JA Onomichi General Hospital in Hiroshima, Japan. RESULTS: PPC confirmed patency of the small intestine in 15 of the 19 patients. Of these 15 patients, 14 proceeded to ON-CE. The CE was cancelled in 1 patient and the cecal intubation time exceeded 8 h in another patient. For the remaining 12 patients, the mean small intestine observation coverage was 92.3% and the mean cecal intubation time was 325 min. There were no adverse events and the discharge of the capsule was confirmed in all cases. CONCLUSION: When patency of the gastrointestinal tract was confirmed with the PPC, ON-CE was performed safely and effectively.

Safety and Effectiveness of Lenvatinib in Patients with Unresectable Hepatocellular Carcinoma in Real-World Clinical Practice: An Observational Post-Marketing Study in Japan.

BACKGROUND: Lenvatinib was approved for use in unresectable hepatocellular carcinoma (uHCC) in Japan in 2018. Patients with diverse clinical characteristics receive lenvatinib treatment in clinical practice. Thus, it is crucial to evaluate the safety and effectiveness of lenvatinib in real-world clinical settings. OBJECTIVE: This study aimed to evaluate the real-world safety and effectiveness of lenvatinib for uHCC in clinical practice in Japan. PATIENTS AND METHODS: Between July 2018 and January 2019, patients with uHCC who were administered lenvatinib for the first time were enrolled in this prospective, multicenter, observational post-marketing study (NCT03663114). Patients were orally administered lenvatinib and followed up for 12 months. For safety, adverse drug reactions (ADRs) were evaluated. For effectiveness, the objective response rate (ORR) was calculated to evaluate tumor response. Overall survival (OS) was estimated using the Kaplan-Meier method. RESULTS: Data of 703 patients (median age, 73 years; 80.2% males) were analyzed. The median (range) treatment duration was 25.3 (0.3-68.9) weeks. The mean ± standard deviation initial dose was 7.37 ± 1.65 mg in patients with body weight < 60 kg and 10.43 ± 2.49 mg in those with body weight ≥ 60 kg. ADRs (any grade) were reported in 84.9% of the patients, with Grade ≥ 3 ADRs reported in 42.5% of the patients. The most common ADRs (> 10%) were decreased appetite, fatigue, hypertension, proteinuria, palmar-plantar erythrodysesthesia, hypothyroidism, and diarrhea. The median OS of the 703 patients was 498.0 days. In 494 patients assessed using the modified Response Evaluation Criteria in Solid Tumors (mRECIST), the ORR was 39.5% (95% confidence interval: 35.1-43.9%). Patients with better liver or renal function at baseline achieved significantly higher ORR than those with worse liver or renal function. CONCLUSIONS: In patients with uHCC in real-world clinical practice in Japan, treatment with lenvatinib was generally well tolerated, and no new safety concerns were identified. The ORR and median OS were similar to or better than the results of the Japanese subset of the global Phase III REFLECT trial. Our results demonstrated that clinically meaningful treatment responses were achieved with lenvatinib in real-world clinical practice.

Acute necrotic disorder of the small intestine post-coronavirus disease-2019 vaccination.

The Pfizer-BioNTech coronavirus disease 2019 (COVID-19) vaccine is extensively used worldwide, and its safety has been proven. Herein, we report a case of an acute necrotic disorder in the small intestine post-COVID-19 vaccination. The patient developed severe abdominal pain the day after the first vaccination. Contrast-enhanced computed tomography showed extensive ileum wall thickening and ascites. Colonoscopy revealed a ring-shaped ulcer and stricture in the terminal ileum. Ileocecal resection was performed, and the patient did not have further episodes of a necrotic disorder in the small intestine. Although it is unknown if this event is associated with vaccination, and this occurrence also does not outweigh the efficacy and safety of the Pfizer-BioNTech COVID-19 vaccine, gastroenterologists need to be aware of this rare case, given its noteworthy timing.

Achievement of sustained viral response after switching treatment from pegylated interferon α-2b to α-2a and ribavirin in patients with recurrence of hepatitis C virus genotype 1 infection after liver transplantation: a case report.

We report a case in which sustained viral response was achieved after switching treatment from pegylated interferon (PEG-IFN) α-2b to α-2a and ribavirin (RBV) in patients with recurrence of hepatitis C virus (HCV) infection after living donor liver transplantation. The patient was a 62-year-old man with liver cirrhosis due to HCV genotype 1b infection. The patient had 8 amino acid (aa) substitutions in the interferon sensitivity-determining region, and had substitutions for mutant and wild-type at aa70 and aa91, respectively, in the core region. The patient had minor genotype (GG) IL28B single nucleotide polymorphisms (rs8099917). He had initially received interferon α-2b and RBV for 2 years, and later developed hepatocellular carcinoma (HCC). After surgical resection of HCC, he subsequently received PEG-IFN α-2b and RBV for 1.5 years, without undetectable viremia during the treatment course. Due to recurrence of HCC, the patient received a living donor liver transplantation. Later on, hepatitis C relapsed. For the management of relapse, he received another course of PEG-IFN α-2b and RBV. However, breakthrough viremia occurred. PEG-IFN was thus switched from α-2b to α-2a and RBV for another 17 months. The patient eventually achieved a sustained viral response.

Long-term outcomes of hepatic arterial port implantation using a coaxial microcatheter system in 176 patients with hepatocellular carcinoma.

The purpose of this study is to evaluate the feasibility of hepatic arterial port implantation using a 2.9-Fr coaxial microcatheter for hepatic arterial infusion chemotherapy (HAIC) in patients with unresectable hepatocellular carcinoma (HCC) in the long-term follow-up period. Our study subjects were 176 patients with unresectable HCC who underwent hepatic arterial port implantation using a 2.9-Fr coaxial microcatheter via the femoral approach. A 2.9-Fr microcatheter with a side hole was introduced into the hepatic artery through a 5-Fr catheter. We determined the possible length of HAIC, starting with hepatic arterial port implantation and ending with the manifestation of technical difficulties or patient death. We also recorded the technical success rate, the time required for the procedure, and the complications encountered. The median duration of HAIC was 4.3 months (range 0.4-51.6 months) and the predictable cumulative rate of hepatic arterial port functioning at 6-, 12-, and 24 months was 75.1%, 60.9%, and 44.6%, respectively. Our technical success rate was 99.4% (175/176), and the mean time required for the procedure was 121 min. Complications were migration of the infusion hole (8.6%, 15/175), hepatic artery damage (5.7%, 10/175), port-catheter system occlusion (5.7%, 10/175), and problems involving the port or the puncture site (8.0%, 14/175). Our study demonstrates that the technical success rate of hepatic arterial port implantation using a coaxial microcatheter was high but that the incidence of port-catheter system occlusion and catheter dislocation was higher than in conventional methods. Our technique is another option to treat patients with HCC for whom conventional techniques cannot be used.

A first case of hepatic angiosarcoma treated with recombinant interleukin-2.

A 60 year-old woman was admitted to our hospital because of management of multiple liver tumors. According to image findings and liver biopsy, she was diagnosed as having epithelioid hemangioendothelioma of the liver accompanied by metastases in the spleen, lungs and bones. Based on the spread of the liver tumors and the extensive systemic metastases, she was considered inoperable. Instead, she received hepatic arterial infusion therapy using recombinant interleukin-2. However, she died due to liver failure about two months after admission. Autopsy revealed that the liver tumor was angiosarcoma. It is difficult to differentiate angiosarcoma from epithelioid hemangioendothelioma based on the image findings and pathological findings of percutaneous liver biopsy. Many cases are diagnosed as angiosarcoma at autopsy. There is no established effective treatment for hepatic angiosarcoma, because the tumor stage at the time of diagnosis is often progressive. To date, immunotherapy with recombinant interleukin-2 has been reported to be effective clinically for cutaneous angiosarcoma, such as of the scalp and facial skin. To our knowledge, there have been no reported cases of hepatic angiosarcoma treated with recombinant interleukin-2. Our case is important should recombinant interleukin-2 be considered effective for hepatic angiosarcoma in the future.

[Significant regression of a cavernous hepatic hemangioma to a sclerosed hemangioma over 12 years: a case study].

A sixties woman was found to have diagnosed by abdominal ultrasonography with a tumor in the left lobe of the liver and was referred to our institution in 1998. Abdominal magnetic resonance imaging (MRI) showed a typical, 70×45 mm cavernous hemangioma, which was followed up by annual MRI. In 2006, 8 years after the initial diagnosis, the MRI showed that the tumor had reduced to 30×15 mm. Although atypical of hemangioma, review of the annual observations indicated a diagnosis of regressive hemangioma, which also accorded with clinical observations. In 2009, a liver biopsy was performed by laparotomy during gastrectomy for gastric cancer. Pathological examination of the biopsy revealed sclerosed hemangioma tissue, confirming the diagnosis of regression of a cavernous hemangioma to a sclerosed hemangioma over 12 years.

Hypersensitivity reactions to transcatheter chemoembolization with cisplatin and Lipiodol suspension for unresectable hepatocellular carcinoma.

PURPOSE: To assess the predictors of hypersensitivity reaction to chemoembolization procedures with cisplatin and Lipiodol suspension for the treatment of hepatocellular carcinoma (HCC). MATERIALS AND METHODS: Between February 2005 and December 2008, 434 patients with HCC were treated with chemoembolization with a cisplatin and Lipiodol suspension. This retrospective cohort study analyzed the incidence of hypersensitivity reactions as an adverse effect and their predictors by multivariate logistic regression analyses. RESULTS: In total, 847 chemoembolization procedures were carried out in 434 patients. The median number of procedures per patient was 2 (range, 1-12). Mean dose of cisplatin per chemoembolization session was 27 mg (range, 15.0-80.0 mg), and the median total dose of cisplatin per patient was 55 mg (range, 5.0-560.0 mg). Hypersensitivity reactions occurred in 14 patients (1.7%). The median number of chemoembolization procedures in these patients was 7 (range, 3-10). Mean dose of cisplatin per session was 22 mg (range, 9.2-35.7 mg), and the median total dose of cisplatin was 134 mg (range, 37-286 mg). On multivariate analysis, the only parameter that showed an independent association with hypersensitivity reactions was the performance of 3 or more than three chemoembolization procedures. CONCLUSIONS: Performance of more than three chemoembolization procedures with a cisplatin and Lipiodol suspension was found to be independently associated with hypersensitivity reactions. Patients undergoing repeated chemoembolization procedures with cisplatin and Lipiodol suspension may experience hypersensitivity reactions as an adverse effect.

Prolongation of interferon therapy for recurrent hepatitis C after living donor liver transplantation: analysis of predictive factors of sustained virological response, including amino acid sequence of the core and NS5A regions of hepatitis C virus.

OBJECTIVE: The aim of the present retrospective study was to evaluate the therapeutic efficacy and predictive factors of prolongation of treatment with peginterferon (PEGIFN) combined with ribavirin (RBV) for recurrent hepatitis C after living donor liver transplantation (LDLT). METHODS: Fifty-three patients underwent LDLT due to HCV-related end-stage liver disease. Sixteen patients were removed from the study as a result of early death (n=14), no recurrence of HCV (n=1) and refusal of antiviral therapy (n=1). Therapy is ongoing in another 10 patients. The remaining 27 patients were available to establish the efficacy of IFN therapy. HCV genotype was 1b in 24 patients. All patients with genotype 1b were treated with IFN therapy for at least 48 weeks after HCV RNA levels had become undetectable. Amino acid substitutions in the HCV core region and NS5A region were analyzed by direct sequencing before LDLT. RESULTS: The rate of sustained virological response (SVR) was 37.0% (10/27). SVR rate in patients with genotype 1 was 29.2% (7/24) and 100% (3/3) in patients with genotype 2. Most patients with genotype 1b whose HCV RNA reached undetectable levels achieved SVR (87.5%; 7/8). However, mutation of the HCV core region and number of ISDR mutations were not associated with SVR rate in LDLT in our study. CONCLUSIONS: Prolonged IFN therapy for more than 48 weeks after HCV RNA reached undetectable levels might prevent virological relapse of HCV.

Percutaneous radiofrequency ablation as first-line treatment for small hepatocellular carcinoma: results and prognostic factors on long-term follow up.

BACKGROUND AND AIMS: We evaluated the prognosis and associated factors in patients with small hepatocellular carcinoma (HCC; up to 3 nodules, each up to 3 cm in diameter) treated with percutaneous radiofrequency ablation (RFA) as first-line treatment. METHODS: Eighty-eight consecutive patients who underwent percutaneous RFA as first-line treatment were enrolled, among whom 70 who had hypervascular HCC nodules which were treated by a combination of transcatheter arterial chemoembolization and RFA. RFA was repeated until an ablative margin was obtained. RESULTS: The rate of local tumor progression at 1 and 3 years was 4.8% and 4.8%, respectively. The rate of overall survival at 3 and 5 years was 83.0% and 70.0%, and the rate of disease-free survival at 3 and 5 years was 34.0% and 24.0%, respectively. On multivariate analysis, age (< 70 years; hazard ratio [HR] = 2.341, 95% confidence interval [CI] = 1.101-4.977, P = 0.027) and indocyanine green retention rate at 15 min (< 15%; HR = 3.621, 95% CI = 1.086-12.079, P = 0.036) were statistically significant determinants of overall survival, while tumor number (solitary, HR = 2.465, 95% CI = 1.170-5.191, P = 0.018) was identified for disease-free survival. Overall survival of patients with early recurrence after RFA was significantly worse than that of patients with late recurrence. Tumor size was the only independent risk factor of early recurrence after RFA of HCC (tumor size > 2 cm; risk ratio [RR] = 4.629, 95% CI = 1.241-17.241, P = 0.023). CONCLUSION: Percutaneous RFA under the protocol reported here has the potential to provide local tumor control for small HCC. In addition to host factors, time interval from RFA to recurrence was an important determinant of prognosis.

Intra-arterial 5-fluorouracil/interferon combination therapy for hepatocellular carcinoma with portal vein tumor thrombosis and extrahepatic metastases.

BACKGROUND AND AIMS: We investigated the efficacy of intra-arterial 5-fluorouracil (5-FU) and systemic interferon (IFN)-alpha (5-FU-IFN) in the treatment of hepatocellular carcinoma (HCC) with portal vein tumor thrombosis in the first branch or trunk (Vp3/4) and extrahepatic metastases. METHODS: We examined 17 HCC patients with Vp3/4 and extrahepatic metastases (meta group) and 31 HCC patients with Vp3/4 (non-meta group). Baseline intrahepatic tumor factors and the hepatic reserve were similar between groups. The extrahepatic metastases of the meta group were not considered prognostic factors. Following the administration of 5-FU/IFN to all patients, we compared the survival rates, response, time to progression (TTP), and safety between groups. RESULTS: For intrahepatic HCC, complete response, partial response, stable disease, progressive disease, and drop out were observed in no (0%), one (6%), seven (41%), nine (53%), and no (0%) patients of the meta group, and in five (16%), seven (23%), 13 (42%), five (16%) and one (3%) patient of the non-meta group, respectively. The response rate was significantly lower in the meta group (6% vs 39%, P = 0.018). The median TTP of intrahepatic HCC and the median survival time were significantly shorter in the meta group than in the non-meta group (1.6 vs 6.3 months, P = 0.0001, and 3.9 months vs 10.5 months, P < 0.0001, respectively). The multivariate analysis showed that the absence of extrahepatic metastases was a significant and independent determinant of both TTP of intrahepatic HCC (P < 0.001) and overall survival (P < 0.001). No patient died of extrahepatic HCC-related disease. CONCLUSIONS: The efficacy of 5-FU/IFN for advanced HCC with Vp3/4 and extrahepatic metastases was markedly limited.

Pilot study of systemic combination therapy with S-1, an oral fluoropyrimidine, and cisplatin for hepatocellular carcinoma with extrahepatic metastases.

BACKGROUND/AIMS: The aim of this pilot study was to elucidate the efficacy and safety of systemic combination therapy with S-1 and cisplatin (CDDP) for hepatocellular carcinoma (HCC) patients with extrahepatic metastases. METHODOLOGY: Sixteen patients were enrolled in this pilot study. Two weeks of combination therapy represented one cycle, followed by two-to-four weeks rest. In each cycle, S-1 was administrated orally at 80-120 mg (depending on body surface area) every day and cisplatin was administrated intravenously at 60 mg/m2 on day 8. Response, overall survival and adverse effects were assessed. RESULT. No patient had intrahepatic HCC and all patients had a class A Child-Pugh score. Regarding overall response, 2 (13%), 0 (0%), 5 (31%), and 9 (56%) patients showed complete response (CR), partial response (PR), stable disease (SD), and progressive disease (PD), respectively, giving an overall response rate of 13% (2/16). The overall survival rate at 12 months was 77%. With regard to NCI-CTC grade-3 adverse reactions, 2 (13%), 2 (13%), and 6 (38%) patients developed nausea, anorexia, and neutropenia, respectively. No grade-4 adverse reaction or toxicity-related death occurred. CONCLUSION; S-1/CDDP is a potentially safe and effective combination therapy for HCC patients with extrahepatic metastases.

Intrahepatic cholangiocarcinoma with clear cell type following laparoscopic curative surgery.

BACKGROUND: Intrahepatic cholangiocarcinoma (ICC) is the second most common malignancy of primary liver cancer. Among the several pathological types of ICC, only five cases of the clear cell type have been reported, including the one presented below. Here we report a unique case of clear cell type ICC following laparoscopic hepatectomy. CASE PRESENTATION: A 67-year-old woman had a history of hepatitis B virus. Computed tomography revealed a ring-like enhanced mass 35 mm in diameter at segment 7 in the early phase. The enhancement was prolonged to the late phase through the portal phase, while the shape was irregular. Ethoxybenzy magnetic resonance imaging revealed that the tumor had a low signal intensity on T1-weighted imaging and a high signal intensity on T2-weighted imaging. Diffusion-weighted images identified that the tumor had remarkably high signal intensity. Tumor enhancement was not detected throughout the tumor in the hepatocyte phase. Upon ICC diagnosis, a laparoscopic S7 subsegmentectomy was performed. The patient's postoperative course was uneventful. An immunohistochemical examination revealed that the cells tested positive for cytokeratin 7 (CK7), CK19, and CD56 and negative for CK20, CD10, α-fetoprotein, thyroid transcription factor-1. At 2 years after surgery, the patient remains alive without recurrence. CONCLUSIONS: Here we presented a case of clear cell ICC that was treated by laparoscopic hepatectomy. Immunological analysis, especially by CD56 and several CK markers, is helpful for diagnosing this disease.

Intra-arterial 5-fluorouracil/interferon combination therapy for advanced hepatocellular carcinoma with or without three-dimensional conformal radiotherapy for portal vein tumor thrombosis.

BACKGROUND: The aim of this study was to elucidate the efficacy of intra-arterial 5-fluorouracil (5-FU) and interferon (IFN) alpha combined with three-dimensional conformal radiotherapy (3D-CRT) for portal vein tumor thrombosis (PVTT). METHODS: The study groups were 16 HCC patients with PVTT treated with 5-FU/IFN combined with 3D-CRT (RT group) and 16 matched controls treated with 5-FU/IFN alone (non-RT group). We compared the survival rate, response, time to progression (TTP), portal hypertension-related events (PREs) and safety. RESULT: Complete response (CR) of PVTT, partial response (PR), stable disease (SD) and progressive disease (PR) were noted in three (19%), nine (56%), four (25%) and zero patients of the RT group, one (6%), three (19%), seven (44%) and five (31%) patients of the non-RT group, respectively. The objective response rate of PVTT was higher in the RT group (P = 0.012). The rate of PREs (variceal rupture, worsening of esophagogastric varices and emerging of uncontrollable ascites) was lower in the RT group than in the non-RT group (P = 0.0195). The median survival time of the RT group (7.5 months) was not significantly different from that of the non-RT group (7.9 months). RT-induced liver disease was not observed. CONCLUSION: 5-FU/IFN combination with 3D-CRT for PVTT improved the response rate of PVTT and reduced the incidence of portal hypertension-related events.

Successful treatment of pulmonary metastases associated with advanced hepatocellular carcinoma by systemic 5-fluorouracil combined with interferon-alpha in a hemodialysis patient.

A 54-year-old man maintained on hemodialysis had a relapse of multiple pulmonary metastases after multimodal therapy for primary hepatocellular carcinoma (HCC). He was treated with tegafur-uracil (UFT; 400 mg/day) and interferon alfa (IFN-alpha; 5 x 10(6) units three times per week) for 4 weeks. Following this he was treated with systemic 5-fluorouracil (5-FU; 1000 mg/day, 5 days per week) and cisplatin (CDDP; 10 mg/day, 5 days per week for 2 weeks). The response to the above treatments was inadequate; pulmonary metastasis deteriorated. Finally, we selected systemic chemotherapy of 5-FU (750 mg/day, 5 days per week) and recombinant IFN-alpha-2b (3 x 10(6) units three times per week) for 2 weeks. This therapy resulted in excellent shrinkage of pulmonary metastases, without severe adverse reactions. Hemodialysis was performed three times a week. We report a case of successful treatment of pulmonary metastases by systemic combination chemotherapy of 5-FU-IFN, previously unsuccessfully treated with UFT-IFN and 5-FU-CDDP in a patient on hemodialysis. Further studies are needed to select appropriate drugs with fluoropyrimidine-based systemic chemotherapy, and to analyze the pharmacokinetics of those agents in hemodialysis patients with HCC and extrahepatic metastases.

The first Japanese case of COACH syndrome.

COACH syndrome is a disorder characterized by hypoplasia of cerebellar vermis, oligophrenia, congenital ataxia, coloboma and hepatic fibrosis, and 21 cases have been reported to date. Here we describe the first Japanese case of COACH syndrome, who was diagnosed at the age of 37 years and never progressed to liver failure. The patient was found to have delayed developmental milestones at the age of 5 months and mental retardation at the age of 7 years. She had been treated for hepatopathy of unknown origin from the age of 22 years. She was admitted to Hiroshima University Hospital at the age of 37 years after the identification of esophageal varices on a routine upper endoscopy. Computed tomography of the abdomen revealed portal hypertension and splenomegaly, and liver biopsy showed liver fibrosis. In addition, she had coordination disorder and dysarthria. Brain magnetic resonance images revealed hypoplasia of cerebellar vermis. The final diagnosis was COACH syndrome. She underwent endoscopic injection sclerotherapy for esophageal varices. From that point until her death from ovarian cancer at the age of 41 years, the liver function tests were stable without an episode of hematemesis. Physicians should be aware of COACH syndrome when they examine young patients who present with hepatopathy, portal hypertension of unknown origin and cerebellar ataxia.

[Case of double cancer of the liver, cholangiocarcinoma and hepatocellular carcinoma detected in a patient with hepatitis C 13 years after diminution of HCV-RNA by interferon treatment].

A 56-year-old man with chronic hepatitis C (HCV) was treated with interferon therapy and achieved sustained virological response (SVR) in 1993. Thirteen years later, in 2006 two liver tumors, 35-mm and 11-mm in diameter respectively, were detected in liver segment 6. Hepatic resection was performed, and pathologically one nodule was diagnosed as cholangiocellular carcinoma (CCC) and the other hepatocellular carcinoma (HCC). Continuity was not recognized between these tumors, thus, we diagnosed this case as double cancer (CCC and HCC). Here, we report a rare case of double cancer (CCC and HCC) that developed 13 years after achieving SVR for HCV infection.