Multiple-needle insertion method in percutaneous ethanol injection therapy for liver neoplasms

One of the shortcomings of percutaneous ethanol injection therapy (PEIT) is that many sessions are necessary to accomplish the treatment. In order to reduce the number of treatment sessions, we inserted two or three needles before injection of ethanol was begun. Using the multiple-needle insertion method, we markedly reduced the number of treatment sessions. Histopathologic examination, imaging techniques, and serum alpha-fetoprotein levels showed efficacy of PEIT using the multiple-needle insertion method. No serious complication occurred. Levels of transient pain, fever, and the feeling of intoxication did not seem to be different from those occurring with the conventional method. Multiple-needle insertion method may be valuable as a method for reducing the number of treatment sessions necessary and thus shortening the treatment period.     

An overview of gastrointestinal and hepatobiliary diseases in Thailand

This review article discusses the present state of gastrointestinal and hepatobiliary diseases in Thailand. Comparisons are made with Western countries and more specific diseases such as hepatoma, cholangiocarcinoma and liver abscesses are also described.     

Local injection therapy for hepatocellular carcinoma

BACKGROUND: Hepatocellular carcinoma (HCC) is one of the most common malignant tumors in the world and ranks the third most common cause of cancer-related death. Surgical resection, liver transplantation and percutaneous ablation are generally considered the only curative treatment for early stage HCC. Besides the limitations of insufficient organ donors and a long waiting time for liver transplantation, however, resection is applied only to patients with good hepatic reserve and localized tumors, with a resectability of 30%. DATA SOURCES: Local ablation therapy, which is minimally invasive but contributes to the significant improvement of survival in patients with unresectable tumor, hasbeen widely used in treating small HCC. Among the techniques of local therapy, percutaneous ethanol injection (PEI) with a complete response in 80% of HCCs less than 3 cm has been accepted as an alternative to surgery in patients with small HCC. Moreover, percutaneous hepatic quantified ethanol injection (PHQEI) or PEI according to the standard criteria has been confirmed to benefit patients with HCC, especially when quantified ethanol is given at a short interval (QESI, the interval was 2-3 days). RESULT: Several limitations related to local percutaneous methods may result in incomplete therapeutic effect in case of larger HCC nodules (>3 cm). CONCLUSION: The combined use of different methods according to the clinical status of patients or tumors may be essential to the effective treatment of HCC.     

HCV and HBV coexist in HBsAg-negative patients with HCV viraemia: Possibility of coinfection in these patients must be considered in HBV-high endemic area

Hepatocellular carcinoma (HCC) is one of the most common cancers and is highly associated with hepatitis B virus (HBV) infection in Korea. The role of HBV and hepatitis C virus (HCV) in HCC patients who are negative for hepatitis B surface antigens (HBsAg) remains poorly defined. It has been suggested that HCV core protein may impair the polymerase activity of HBV in vitro, potentially lowering HBV titre in coinfected patients. Therefore, routine enzyme immunoassay may not detect HBV, in spite of the presence of HBV viraemia in low titres. The aim of this study was to confirm the coexistence of HBV viraemia in hepatitis C-infected patients with HCC who have apparent HBsAg seronegativity and to establish the need for clinical reinterpretation of enzyme immunoassay (EIA) serological tests of HBsAg in patients with HCV viraemia and HCC. The serological profiles of HBV and HCV in 616 patients with HCC were analysed and the coinfection rate of HCV and HBV investigated. Sera were obtained from 16 patients who were both anti-HCV and HCV-RNA positive but HBsAg negative, and tested for HBV by polymerase chain reaction (PCR). Eleven non-A and non-B chronic hepatitis patients without HCC who had the same profiles of anti-HCV, HCV-RNA, and HBsAg were tested for HBV by PCR. As a control group, sera were obtained from 15 patients with HCC and 30 non-A and non-B chronic hepatitis patients without HCC; both were anti-HCV, HCV-RNA, and HBsAg negative and tested for HBV PCR. Of the 616 patients with HCC, 450 (73.1%) had current HBV infection, 48 (7.8%) had anti-HCV antibodies, and nine (1.5%) had viral markers of both HCV and HBV by serological profiles. Of the 27 patients with HCV viraemia and HBsAg seronegativity (16 with HCC; 11 with non-A non-B chronic hepatitis), 14 (51.9%) showed HBV viraemia by PCR. In contrast, of the 75 patients in the control group (45 with HCC; 30 with non-A and non-B chronic hepatitis) who were both HCV PCR negative and HBsAg negative, five (11.1%) showed HBV viraemia by PCR. The PCR for HBV revealed coexistent HBV viraemia in HCV viraemia patients, despite HBsAg negativity by EIA. In HBV-endemic areas, the possibility of coinfection of HBV in HBsAg-negative patients with HCV viraemia should be considered and molecular analysis for HBV-DNA performed.     

Hepatocellular carcinoma with sarcomatous change arising in primary biliary cirrhosis

We report an autopsy case of hepatocellular carcinoma (HCC) with sarcomatous change arising in the context of primary biliary cirrhosis (PBC) in a 79-year-old man. Primary biliary cirrhosis was diagnosed (stage I according to Scheuer's classification) by findings on blood biochemical analysis, laparoscopy, and liver biopsy at age 69 years. Five years later, (at age 74 years), a mass lesion was detected in the S₆ region of the liver by abdominal ultrasonography, and target biopsy revealed well differentiated HCC. Blood biochemistry, ultrasonography, and computed tomography findings showed that the PBC had progressed to stage IV (cirrhotic stage). Percutaneous ethanol injection therapy (PEIT) was administered to the HCC several times over a 5-year period; however, the patient died of liver failure in February, 1994 (at age 79 years). Viral markers for hepatitis B and C were negative during the course, and hepatitis C virus RNA was not detected by polymerase chain reaction. Autopsy findings showed liver cirrhosis and diffuse involvement of spindle-shaped sarcomatoid cells in the liver, particularly in the S₆ region, associated with several nodules of trabecular HCC cells. A zone of transition between the sarcomatoid cells and the trabecular hepatocellular carcinoma cells was observed. The sarcomatoid cells were diffusely disseminated in the peritoneal cavity and had metastasized to multiple organs. Immunohistochemically, the cells were positive for fibrinogen, as were the coexisting trabecular hepatocellular carcinoma cells. The HCC had been treated several times with PEIT. Of interest, PEIT may be an important factor in this type of tumor progression.     

Intra-arterial carbon dioxide-enhanced ultrasonogram of hepatocellular carcinoma treated by transcatheter arterial embolization and percutaneous ethanol injection therapy

The purpose of this study was to investigate the value of carbon dioxide-enhanced ultrasonography (CO₂-US) in the evaluation of viable hepatocellular carcinomas (HCC) which were treated by transcatheter arterial embolization (TAE), percutaneous ethanol injection (PEI), or a combination treatment (TAE and PEI). Forty-one patients with 66 HCC were included in the study. They underwent CO₂-US and angiography were performed in all tumours after they were treated by TAE, PEI or a combination treatment. Forty-six tumours were positively enhanced by CO₂-US and 40 of them were positive by angiography. These 46 tumours were proved to be viable tumours either by biopsy or by follow-up studies. The positive predictive value was 100% for CO₂-US and 87.8% in angiography. Twenty tumours were negative by CO₂-US and these were also negative by angiography. Carbon dioxide-enhanced ultrasonography is a more reliable method for detecting the viable portion of the treated HCC compared with conventional angiography.     

Persistent retention of acetic acid is associated with complete tumour necrosis in patients with hepatocellular carcinoma undergoing percutaneous acetic acid injection

Background: Ultrasound (US)‐guided percutaneous acetic acid injection therapy (PAIT) is effective for patients with hepatocellular carcinoma (HCC). This study aimed to determine the occurrence and predictive value of persistent intra‐tumoral retention of acetic acid after PAIT. Methods: We prospectively studied 60 (52 M, mean age 68?±?10 years) patients with 72 HCC nodules (45?≤?3?cm) treated with PAIT. The presence of post‐treatment persistent retention of acetic acid, defined as a homogeneous and highly hyperechoid mass in US appearance 3 days after completion of the treatment, was correlated with the treatment response. Results: The mean size of the treated tumour was 2.9?±?1.0?cm (range 1.5–5?cm). Thirty (42%) HCC nodules showed complete tumour necrosis demonstrated by contrast‐enhanced dynamic CT. Complete response was found in 22 (69%) of 32 nodules showing persistent intra‐tumoral retention of acetic acid (P?P?=?0.001). There were no significant differences of the injection volume and treatment sessions between those with and without complete tumour necrosis in either small or large (>3?cm) HCC (P?>?0.1). Multivariate logistic regression analysis showed that persistent retention of acetic acid (odds ratio (OR) 10.4, 95% confidence interval (CI) 3.1–34.7; P?P?=?0.002) were independent factors predicting complete tumour necrosis. Conclusions: The presence of persistent retention of acetic acid is associated with a favourable response and may predict complete tumour necrosis after PAIT.     

Percutaneous ethanol injection for the treatment of small hepatocellular carcinoma. Study of 95 patients

Percutaneous ethanol injection (PEI) was applied to 120 lesions in 95 patients with hepatocellular carcinomas (HCC) smaller than 3 cm in the past 6 years. All main target tumours, in 67 patients who had been followed by sonography for more than 6 months after PEI, decreased in size; 28 tumours (41.8%) became undetectable and have remained so until now. The 1-, 2-, 3-, 4- and 5-year survival rates calculated by the Kaplan-Meier method were 93%, 81%, 65%, 52% and 28% respectively. These survival rates were better than those of patients with HCC smaller than 3 cm who did not receive anticancer treatment (P less than 0.01). The survival of patients of the Child's A or Child's B status was better than that of those with Child's C disease. Recurrence occurred in areas within the liver different from the original lesion in 34% in one year, 61% in two years and 66% in three years after PEI. PEI was then repeated in 61% of such patients.     

Altered biliary epithelial cell and monocyte responses to lipopolysaccharide as a TLR ligand in patients with primary biliary cirrhosis

Objective. Many reports indicate the importance of active treatment for hepatocellular carcinoma (HCC), but there are few studies available that address the impact of delayed therapy on survival or take the lead-time bias into account. The objective of this study was to investigate whether patients with delayed locoregional therapy for HCC truly have a shortened survival from the time of diagnosis. Material and methods. Survival rates were compared between 48 HCC patients with treatment delay and 96 age- and gender-matched controls without delay. All patients underwent transarterial chemoembolization or percutaneous ethanol or acetic acid injection for HCC. Treatment delay was defined as a >2 months’ time interval between diagnosis and treatment. Results. Baseline comparison showed that patients with treatment delay had higher scores in the model for endstage liver disease compared with those of patients without delay (12.3±1.8 versus 11.1±2.5, p=0.01). In the Cox multivariate model, advanced cancer stage (relative risk (RR): 2.66, p=0.001), Child-Turcotte-Pugh class B (RR: 3.81, p<0.001), tumor size >5 cm (RR: 2.02, p=0.011) and treatment delay (RR: 2.91, p=0.001) were independent poor prognostic predictors. Among patients with treatment delay, disease progression was registered in 30 (63%) patients. Patients with prolonged treatment delay (>3 months) were more likely to have tumor progression (p=0.013). In the Cox model, a treatment delay of >3 months independently predicted a poor rate of survival (RR: 3.67, p=0.002). Conclusions. Delayed HCC treatment is linked with shortened overall survival unrelated to the lead-time bias in patients undergoing locoregional therapy. Prolonged treatment delay of more than 3 months in these patients may worsen the long-term outcome.     

Outcome of transarterial chemoembolization monotherapy, and in combination with percutaneous ethanol injection, or radiofrequency ablation therapy for hepatocellular carcinoma

Aim:  Hepatocellular carcinoma (HCC) is one of the most commonly occurring malignances worldwide. Curative therapies such as resection, percutaneous ethanol injection (PEI) and radiofrequency ablation (RFA) have been applied to patients with early-stage HCC. Patients with more advanced cancers require local or systemic therapies. We present the results of our retrospective review conducted to evaluate whether transarterial chemoembolization (TACE) alone and combined TACE with percutaneous ablation for HCC exhibited superior efficacy to palliative treatment.
Methods:  The effects of TACE and of the combined therapies (TACE + PEI or TACE + RFA) on the long-term survival rates were evaluated in 268 untreated HCC patients by various statistical analyses.
Results:  The cumulative survival rates in the TACE alone group were significantly superior to those in the palliative treatment group. Further, the cumulative survival rates in the combined TACE + PEI/RFA group were significantly superior to those in the TACE alone group. When the comparison among the groups was restricted to patients with two or three tumors fulfilling the Milan criteria, significantly greater prolongation of survival was observed in the combined TACE + PEI/RFA group than in the PEI/RFA alone group.
Conclusions:  The aforementioned treatment modalities yielded greater improvements of the survival rate and survival duration as compared to palliative treatment in HCC patients. Furthermore, in terms of the effect on the survival period, combined TACE + PEI/RFA therapy was more effective than TACE monotherapy, and also more effective than PEI or RFA monotherapy in cases with multiple tumors fulfilling the Milan criteria.     

An enormous hepatitis B virus‐related liver disease burden projected in Vietnam by 2025

Background: Hepatitis B virus (HBV) is the major cause of chronic liver disease in Vietnam. This study aimed to estimate and project chronic HBV prevalence and HBV‐related liver cirrhosis (LC) and hepatocellular carcinoma (HCC) for the period 1990–2025. Method: The Vietnamese population for the period 1990–1999 was derived from census data to 1999 and from 2000 to 2025 based on projection data from the United States Census Bureau. Population chronic HBV prevalence for males and females was estimated based on age‐specific HBV prevalence from Vietnamese community‐based studies. Universal infant HBV vaccination from 2003 was assumed to reduce HBV infection by 90% in subsequent birth cohorts. Incidences of HBV‐related LC and HCC by HBV DNA levels from the Taiwanese REVEAL studies were applied to the chronic HBV population to estimate and project HBV‐related liver disease burden. Results: Estimated chronic HBV prevalence increased from 6.4 million cases in 1990 to around 8.4 million cases in 2005 and was projected to decrease to 8.0 million by 2025. Estimated HBV‐related LC and HCC incidence increased linearly from 21 900 and 9400 in 1990 to 58 650 and 25 000 in 2025. Estimated HBV‐related mortality increased from 12 600 in 1990 to 40 000 in 2025. Conclusion: Over the next two decades, universal infant HBV vaccination will reduce chronic HBV prevalence in Vietnam but HBV‐related liver disease burden will continue to rise. A national HBV strategy is required to address this expanding burden of liver disease.     

循环miRNA在肝胆疾病诊断中的研究进展

微小核糖核酸(microRNA),简称miRNA,参与着生命活动的病理生理过程,在人体血清、血浆等体液中存在丰富而稳定的循环miRNA。简述了循环miRNA与病毒性肝炎、肝纤维化、肝硬化、肝癌、药物性肝炎等肝胆疾病或疾病不同阶段的表达谱存在明显差异性,其中一些循环miRNA可作为相关疾病早期诊断、病情进展和预后评估的新型无创性生物标志。本文就循环miRNA在肝胆疾病诊断研究中的最新进展作一综述。     

中西医结合治疗常见肝胆胰疾病的现状与展望

目前中西医结合诊疗形式主要是中医药治疗或中药与西药联合使用两种状态,均用现代诊断和疗效评价,虽缺乏理论突破,但在临床、科研实践中有了更多共识和创新。归纳和评述近10年来常见肝胆胰疾病治疗领域的临床、科研现状,采纳临床有明确疾病诊断且经过重大科研课题或有循证医学证据的疗效、成果,以及在核心期刊发表的论文。力求客观反映当前中西医结合治疗肝胆胰疾病的优效和研究热点,以期对本领域临床和科研有所启发。     

Evidence-based medicine in the treatment of hepatocellular carcinoma

The incidence of hepatocellular carcinoma is increasing worldwide. Diagnosis at early stage is crucial to allow the application of curative treatments, that are the sole hope to increase their life expectancy. Surgical resection and liver transplantation are considered the first line options for early tumors, although there is no agreement on which is the best treatment approach. Resection achieves excellent results in patients with single tumors, absence of portal hypertension and normal bilirubin, but is limited by the high recurrence rate. Liver transplantation also achieves excellent results in patients with single tumors smaller than 5 cm or even three nodules smaller than 3 cm. However, this procedure is hampered by the shortage of donors and the increasing waiting times that have reduced their intention-to-treat outcomes. Treatment while waiting for a donor is controversial, but radical antitumoral therapies seem cost-effective in long waiting times. Percutaneous therapies are reserved for patients with single non-surgical tumors. More than 60 randomized clinical trials have been published to assess treatments for patients with advanced tumors, but there is no definitive evidence of survival benefits. A recent randomized trial reported that chemoembolization may benefit HCC patients in terms of survival, but additional studies to confirm this data are recommended.     

Management of inoperable hepatocellular carcinoma

Abstract   Hepatocellular carcinoma (HCC) is a common and difficult-to-treat malignant tumor. Surgical interventions are feasible in only a small proportion of patients, and non-surgical therapy has been frequently administered to patients with inoperable HCC. Various modalities of loco-regional therapy have gained much interest during the past decade. Among them, transarterial chemoembolization (TACE), percutaneous injection of ethanol (PEI) or acetic acid (PAI), radiofrequency ablation (RFA) and microwave coagulation therapy (MCT) are effective treatment options. TACE can target multiple hypervascular tumors but has the potential risk of inducing hepatic or renal failure. PEI is a well-established method for small (< 3 cm) HCC, and PAI has the advantage over PEI as being more effective with fewer treatment sessions. RFA has excellent tumor ablation ability, and has been extended to treat medium- or large-sized HCC. However, the overall complication rate may be higher than previously assumed. MCT is similar to RFA in its clinical application and adverse effects. Although combination therapy often achieves a higher response rate, the side-effects may also be additive. Other therapies, such as injection of hot saline or yttrium-90 microspheres, interstitial laser photocoagulation and cryoablation are seldom used nowadays. Thalidomide may be useful in a minority of HCC patients, whereas radiotherapy, chemotherapy and tamoxifen are generally ineffective. In conclusion, although long-term survival in patients with inoperable HCC is possible in selected patients, the overall prognosis remains unsatisfactory, especially in those with aggressive tumor behavior. Newer antitumor therapy with better treatment efficacy is urgently needed. Information of the design for a more comprehensive approach using the existing therapeutic options may help refine the treatment strategy.     

Radiofrequency ablation versus ethanol injection for early hepatocellular carcinoma: A randomized controlled trial

Objective. To compare percutaneous ethanol injection (PEI), the standard approach which has been used for many years to treat early non-surgical hepatocellular carcinoma (HCC) in cirrhotic patients, and radiofrequency ablation (RFA), which has become an interesting alternative. Material and methods. A randomized trial was carried out on 139 cirrhotic patients in Child-Pugh classes A/B with 1–3 nodes of HCC (diameter 15–30 mm), for a total of 177 lesions. Patients were randomized to receive RFA (n=70) or PEI (n=69). The primary end-point was complete response (CR) 1 year after the percutaneous ablation of all HCC nodes identified at baseline. Secondary end-points were: early (30–50 days) CR, complications, survival and costs. Results. In an intention-to-treat analysis, 1-year CR was achieved in 46/70 (65.7%) and in 25/69 (36.2%) patients treated by RFA and PEI, respectively (p=0.0005). For lesions >20 mm in diameter, there was a larger CR rate in the RFA group (68.1% versus 26.3%). An early CR was obtained in 67/70 (95.7%) patients treated by RFA compared with 42/64 (65.6%) patients treated by PEI (p=0.0001). Complications occurred in 10 and 12 patients treated by RFA and PEI, respectively. The overall survival rate was not significantly different in the RFA versus PEI arm (adjusted hazard ratio=0.88, 95% CI: 0.50–1.53). There was an incremental health-care cost of 8286 € for each additional patient successfully treated by RFA. Conclusions. The 1-year CR rate after percutaneous treatment of early HCC was significantly better with RFA than with PEI but did not provide a clear survival advantage in cirrhotic patients.     

Portal vein thrombosis complicating hepatocellular carcinoma. Value of ultrasound-guided fine-needle biopsy of the thrombus in the therapeutic management

Abstract: During a 4-year period portal vein thrombosis was diagnosed in 20 Child class A patients with cirrhosis by means of ultrasound and ultrasound-Doppler study. Seventeen of them showed single or multiple focal liver lesions diagnosed as hepatocellular carcinoma by ultrasound-guided fine-needle biopsy and the remaining three a coarse liver echo-pattern without focal lesions. One patient was found to have developed portal vein thrombosis after the fifth ethanol injection of a single hepatocellular carcinoma lesion 17 mm in diameter. Ultrasound-guided fine-needle biopsy of the thrombus was performed on all the patients: portal vein thrombosis was neoplastic in 13 cases and non-neoplastic in seven cases (five patients with a single lesion; one with two lesions; one with coarse liver echo-pattern). Among the five patients with a single lesion, one had already been treated by percutaneous ethanol injection therapy. There were no complications related to the biopsy procedures. The diagnosis of non-neoplastic thrombosis allowed five new patients to be recruited for percutaneous ethanol injection treatment and allowed it to continue in the patient with portal vein thrombosis occurring after the fifth ethanol injection. The routine use of ultrasound-guided fine-needle biopsy of portal vein thrombosis yields an accurate diagnosis of the nature of the thrombus and can improve the selection for percutaneous ethanol injection treatment of patients with cirrhosis with hepatocellular carcinoma lesions.     

MRI在肝胆疾病中的应用及挑战

我国肝胆疾病高发,且多样化。除慢性病毒性肝炎外,非酒精性脂肪性肝病及酒精性肝病的发生率亦逐年上升。近年来,随着MRI软硬件技术的改进、参数的个性化选择、脉冲序列的变换组合、新型造影剂的使用等,MRI已成为肝胆疾病诊断不可替代的检查手段,但仍面临挑战,重点评述了MRI在肝胆脏疾病中的应用进展和研究难点,探讨进一步提高临床研究水平的发展前景。     

The Islanding effect - a special method of percutaneous peritumor ethanol injection for hepatocellular carcinoma: 15-year follow-up outcome

Percutaneous ethanol injection is a well-known ablation therapy for hepatocellular carcinoma and is well-tolerated, inexpensive, and effective with few adverse events. In this study, another type of ethanol injection was introduced in the present study.Sixty two patients with hepatocellular carcinoma received 133 percutaneous peritumor ethanol injection treatments and the 15-year follow-up outcomes were analyzed through a collected database.The technical efficiency was 89.5% (119/133 treatments) after the first percutaneous peritumor ethanol injection procedure. However, after the second repeated percutaneous peritumor ethanol injection procedure, technical efficiency increased to 98.5% (131/133 treatments). The 1 year, 3 years, 5 years, 10 years, and 15 years rates of tumor recurrence were 12.9%, 50.0%, 59.7%, 74.2%, and 74.2%, respectively. Multivariate analysis demonstrated that diabetes, Child–Pugh class B, and tumor size greater than 2 cm were significantly related to tumor recurrence. The 1 year, 3 years, 5 years, 10 years, and 15 years rates of overall survival were 98.4%, 83.6%, 61.3%, 19.4%, and 0%, respectively. Multivariate analysis demonstrated that Child–Pugh class B, tumor size greater than 2 cm, and multiple tumors were significantly related to overall survival.Compared with other ablation methods (including peritumor ethanol injection), percutaneous peritumor ethanol injection can avoid tumor ruptures, reduce tumor proliferation and metastasis, and is suitable for the treatment of small tumors. In addition, when combined with other treatment methods, percutaneous peritumor ethanol injection can form a tumor metastatic isolation zone in advance and improve the comprehensive treatment effect.