Multiple gut-liver axis abnormalities in children with obesity with and without hepatic involvement.

BACKGROUND: Gut-liver axis (GLA) dysfunction appears to play a role in obesity and obesity-related hepatic complications. OBJECTIVES: This study sought to concurrently explore several GLA components in a paediatric obese population with/without liver disease. METHODS: Thirty-two children (mean age 11.2 years) were enrolled: nine controls with normal weight and 23 patients with obesity (OB+). Of the 23 patients OB(+), 12 had not steatosis (ST-), and 11 had steatosis (ST+) (associated [n = 8] or not [n = 3] with hypertransaminasaemia [ALT +/-]). Subjects were characterized by using auxologic, ultrasonographic and laboratory parameters. A glucose hydrogen breath test was performed to test for small intestinal bacterial overgrowth, a urinary lactulose/mannitol ratio (LMR) was obtained to assess intestinal permeability, and tests for transaminases, blood endogenous ethanol, endotoxin and faecal calprotectin were also conducted. RESULTS: Eleven out of 23 patients OB(+) (p < 0.05) exhibited pathological (>90th percentile of the control group values) LMR, with values paralleling the grade of liver involvement (normal weight < OB[+] < OB[+]ST[+]ALT[-] < OB[+)]ST[+]ALT[+] [p < 0.05]). LMR significantly correlated with ethanolaemia (r = 0.38, p = 0.05) and endotoxaemia (r = 0.48, p = 0.015) concentrations. Increased permeability was a risk factor for the development of steatosis (p < 0.002). SIBO was present only in patients with obesity. Faecal calprotectin concentrations were within normal limits in all subjects. CONCLUSIONS: Increased permeability, endogenous ethanol and systemic endotoxin concentrations reflect some GLA dysfunction in obesity and its hepatic complications. Pending further results to establish their potential causative roles, the modulation of the GLA appears to represent a possible target for the prevention and treatment of these conditions.

Imaging detection of new HCCs in cirrhotic patients treated with different techniques: Comparison of conventional US, spiral CT, and 3-dimensional contrast-enhanced US with the Navigator technique (Nav 3D CEUS)().

INTRODUCTION: The commercially available Navigator system(©) (Esaote, Italy) allows easy 3D reconstruction of a single 2D acquisition of contrast-enhanced US (CEUS) imaging of the whole liver (with volumetric correction provided by the electromagnetic device of the Navigator(©)). The aim of our study was to compare the efficacy of this panoramic technique (Nav 3D CEUS) with that of conventional US and spiral CT in the detection of new hepatic lesions in patients treated for hepatocellular carcinoma (HCC). MATERIALS AND METHODS: From November 2006 to May 2007, we performed conventional US, Nav 3D CEUS, and spiral CT on 72 cirrhotic patients previously treated for 1 or more HCCs (M/F: 38/34; all HCV-positive; Child: A/B 58/14) (1 examination: 48 patients; 2 examinations: 20 patients; 3 examinations: 4 patients). Nav 3D CEUS was performed with SonoVue(©) (Bracco, Milan, Italy) as a contrast agent and Technos MPX(©) scanner (Esaote, Genoa, Italy). Sensitivity, specificity, diagnostic accuracy, and positive and negative predictive values (PPV and NPV, respectively) were evaluated. Differences between the techniques were assessed with the chi-square test (SPSS release-15). RESULTS: Definitive diagnoses (based on spiral CT and additional follow-up) were: 6 cases of local recurrence (LocRecs) in 4 patients, 49 new nodules >2 cm from a treated nodule (NewNods) in 34 patients, and 10 cases of multinodular recurrence consisting of 4 or more nodules (NewMulti). The remaining 24 patients (22 treated for 1-3 nodules, 2 treated for >3 nodules) remained recurrence-free. Conventional US correctly detected 29/49 NewNods, 9/10 NewMultis, and 3/6 LocRecs (sensitivity: 59.2%; specificity: 100%; diagnostic accuracy: 73.6%; PPV: 100%; NPV: 70.1%). Spiral CT detected 42/49 NewNods plus 1 that was a false positive, 9/10 NewMultis, and all 6 LocRecs (sensitivity: 85.7%; specificity: 95.7%; diagnostic accuracy: 90.9%; PPV: 97.7%; NPV: 75.9%). 3D NAV results were: 46N (+9 multinodularN and 6 LR), 3 false-negatives, and one false-positive (sensitivity: 93.9; specificity: 97.9%; diagnostic accuracy: 95.6; PPV: 97.9; NPV: 93.9). CONCLUSIONS: 3D Nav CEUS is significantly better than US and very similar to spiral CT for detection of new HCCs. This technique revealed the presence of lesions that could not be visualized with spiral CT.

Percutaneous radiofrequency ablation of small hepatocellular carcinoma: long-term results.

The aim of this study was to evaluate the effectiveness and the safety of percutaneous radiofrequency (RF) thermal ablation of hepatocellular carcinoma (HCC) in 88 patients with a long follow-up, and to compare conventional electrodes and expandable electrodes. Eighty-eight patients with 101 hepatocellular carcinoma nodules (< or = 3.5 cm in diameter) underwent RF thermal ablation by means of either conventional electrodes or an expandable electrode. Therapeutic efficacy was evaluated with dynamic contrast CT, serum alpha-feto protein level, US examination at the end of the treatment, and during follow-up. Complete necrosis was obtained in all tumor nodules in a mean number of 3.3 sessions (tumor treated by conventional electrodes) or 1.5 sessions (tumor treated by expandable electrode). The mean follow-up was 34 months; overall survival rate was 33% at 5 years. Disease-free survival at 5 years was 3%; local recurrence rate was 29% in patients treated with conventional electrodes; 14% in patients treated with the expandable electrode. Two major complications and 14 minor complications were observed. Radiofrequency thermal ablation in small HCC is very effective with a low percentage of major complications. The use of an expandable electrode substantially reduced the number of treatment sessions but did not modify the overall survival rate and the disease-free survival rate.

Peroxynitrite-dependent activation of src tyrosine kinases lyn and hck in erythrocytes is under mechanistically different pathways of redox control.

Peroxynitrite, the product of superoxide and nitric oxide radicals, is considered one of the major oxidants formed in vivo under intense oxidative stress. We have previously reported the upregulation by peroxynitrite of src kinase activity in red blood cells. In this study, we investigated the mechanisms of peroxynitrite action and we demonstrate that two src kinases (lyn and hck) are activated through different pathways involving cysteine-dependent or -independent oxidations. Activation of hck by peroxynitrite or by hydrogen peroxide could be explained by reversible SH redox changes, whereas lyn was unaffected by hydrogen peroxide and its direct activation by peroxynitrite occurred through a still unknown modification(s) not reverted by SH reduction or inhibited by SH alkylation. Moreover, lyn could be activated also downstream by peroxynitrite-activated hck. The cross talk between lyn and hck was selective, since activated hck did not activate the non-src kinase syk. This study illustrates the complexity of redox-dependent src regulation and suggests that one reason for src heterogeneity may be a peculiar difference in their sensitivity to physiological oxidants. Irrespectively of the activation pathway, the final effect of peroxynitrite is the amplification of tyrosine-dependent signaling, a finding of general interest in nitric oxide-related pathophysiology.

Long-term survival of stage I multiple myeloma given chemotherapy just after diagnosis or at progression of the disease: a multicentre randomized study. Cooperative Group of Study and Treatment of Multiple Myeloma.

We conducted a randomized trial to evaluate whether melphalan-prednisone (MPH-P) treatment administered just after diagnosis improves survival of stage I multiple myeloma (MM). Between January 1987 and March 1993, 145 consecutive previously untreated patients with stage I MM were randomized between treatment with MPH-P (administered for 4 days every 6 weeks) just after diagnosis and treatment only at disease progression. Survival was not influenced by MPH-P treatment either administered just after diagnosis or at disease progression (64 vs 71 months respectively). Comparing the first with the second group the odds ratio of death is 1.17 (95% confidence interval 0.57-2.42; P = 0.64). Disease progression occurred within a year in about 50% of patients who were initially untreated. Response rate was similar in both groups, but duration of response was shorter in patients who were treated at disease progression (48 vs 79 months, P = 0.044). Patients actually treated at disease progression (34/70) survived shorter than those who had neither disease progression nor treatment (56 vs > 92 months; P = 0.005). Starting MPH-P just after diagnosis does not improve survival and response rate in stage I MM, with respect to deferring therapy until disease progression. However, patients with stage I MM randomized to have treatment delayed and who actually progressed and were treated had shorter survival than those with stable disease and no treatment. Biologic or other disease features could identify these subgroups of patients.

Percutaneous radiofrequency thermal ablation combined with transcatheter arterial embolization in the treatment of large hepatocellular carcinoma.

PURPOSE: To evaluate whether the combination of hepatic segmental transcatheter arterial embolization (TAE) with percutaneous radiofrequency (RF) ablation can increase the volume of coagulation necrosis to treat patients with large hepatocellular carcinoma (HCC). METHOD: Fourteen patients with cirrhosis and HCC whose greatest diameter ranged from 3.8 to 6.8 cm (mean, 5.2 cm) underwent segmental TAE followed within 3 days by RF interstitial thermal ablation with an expandable needle electrode inserted into the tumour under sonographic guidance, after local anesthesia. We made one or more needle electrode insertions depending on tumor shape. Posttreatment necrosis was evaluated by ultrasonography, dynamic computed tomography (CT) and alpha-fetoprotein dosage in all cases, repeated every three to four months. RESULTS: Tumor ablation was obtained in one session in 11 (78%) patients (with one needle electrode insertion in 8 patients), in two sessions in 1, in three sessions in 2. In a mean follow-up of 13.2 months (range 6-23) two patients died from unrelated causes; one patient showed multinodular HCC 6 months after the treatment; 4 patients developed new lesions, treated by a new course of RF ablation (3 cases) or by surgery (1 case); therefore 11/12 patients still in follow-up were disease-free. No fatal complications were observed. One month after the treatment, fluid collection at the site of the ablated tumor was observed in one patient which was percutaneously drained. CONCLUSIONS: Percutaneous RF thermal ablation performed after TAE effectively treated HCCs larger than tumors suitable for segmental TAE or RF application alone; the result was achieved in two thirds of the cases in a single session with only one needle electrode insertion.

Ultrasound-guided fine needle biopsy of pancreatic masses: results of a multicenter study.

OBJECTIVE: The aim of this study was to investigate the results of ultrasound-guided fine needle biopsy of pancreatic masses in a large multicenter series. METHODS: This study collected the data of 510 patients who had a final diagnosis available and who had undergone ultrasound-guided fine needle biopsy of the pancreas. Retrieval rate, sensitivity, specificity, and overall diagnostic accuracy of the whole series, by three different bioptic procedures (cytology, histology, and cytology plus histology) were evaluated. The reliability of ultrasound-guided fine needle biopsy to allow a correct diagnosis in the different pancreatic pathologies was calculated. Finally, any complications were collected. RESULTS: For cytology, histology, and cytology plus histology, retrieval rate values were: 94%, 96%, and 97%; sensitivity was: 87%, 94%, and 94%, specificity: 100%; and diagnostic accuracy: 91%, 90%, and 95%, respectively. Ultrasound-guided fine-needle biopsy correctly diagnosed all the cases of pancreatic metastases or non-Hodgkin's lymphoma (23 of 510 cases as 5%; in eight of 23 it led to the first diagnosis of the primary tumor) and all the cases of abscesses, 97% of the cases of pseudocysts, 86% of pancreatic adenocarcinomas, 62% of cystic neoplasms, 35% of the cases of chronic pancreatitis (in this case, the bioptic procedures were reviewed), and 33% of neuroendocrine tumors. There were complications in one case of asymptomatic peripancreatic hematoma, three cases of vaso-vagal reactions, and 21 cases of pain. CONCLUSION: Ultrasound-guided fine needle biopsy of the pancreas is efficacious, without any difference between the various bioptic modalities (with the exception of chronic pancreatitis, in which histology is better). The technique is safe. Moreover, the procedure allows the identification of patients affected by pancreatic tumors other than adenocarcinoma (in our survey 5% of the total); in about one third of these patients it leads to the diagnosis of the primary tumor, thus avoiding inappropriate treatments.

Microbiología de 26 casos de peritonitis secundaria de origen no traumático / Microbiology of 26 case of secondary peritonitis of non traumatic origin

Se realizó un estudio clínico prospectivo desde julio 1995 a octubre 1996 incluyendo un total de 26 pacientes que fueron intervenidos quirúrgicamente en el Servicio de Cirugía II del Hospital Vargas de Caracas con el diagnóstico de peritonitis secundaria de origen no traumático penetrante. Se tomó muestra para cultivo de la fuente de infección, en quirófano antes de iniciar la antibioticoterapia. Las patologías que más frecuentemente originaron peritonitis fueron: ulcus péptico perforado, apendicitis aguda perforada y absceso tuboovárico roto. Se obtuvo crecimiento bacteriano en el 73 por ciento de los casos. Se aislaron un total de 30 gérmenes patógenos de las muestras intraabdominales correspondiendo el 50 por ciento de gram negativos; el 13,4 por ciento a gram positivos, el 16,6 por ciento a anaerobios y el 20 por ciento restante a hongos (candida albicans). En el 36,8 por ciento de los casos se aisló más de un gérmen. La antibioticoterapia inicial en los casos de peritonitis secundaria es empírica, utilizando agentes de amplio espectro. Se ha cuestionado la utilidad del cultivo en estos casos por su elevado costo y relativa poca utilidad en la escogencia del antibiótico

Percutaneous treatment of small hepatic tumors by an expandable RF needle electrode.

OBJECTIVE: The aim of this study was to evaluate the usefulness of expandable RF needle electrodes in the treatment of hepatic cancer. SUBJECTS AND METHODS: Thirty-seven patients, 23 of whom had 26 hepatocellular carcinoma nodules and 14 of whom had 19 hepatic metastatic nodules, underwent treatment by RF interstitial thermal ablation with expandable needle electrodes. Forty-five tumor nodules were treated in 64 RF interstitial thermal ablation sessions with 83 needle electrode insertions. The mean diameter of the tumor nodules was 2.5 cm (range, 1.1-3.5 cm). Immediate posttreatment tumor necrosis was evaluated by dynamic CT in all cases. Two patients with hepatocellular carcinoma and three patients with metastases underwent surgical resection 20-60 days after RF treatment. The remaining 32 patients were followed up clinically. RESULTS: The mean number of RF interstitial thermal ablation sessions to complete tumor nodule treatment was 1.4. Mean number of needle electrode insertions was 1.8. No complications were observed. Posttreatment dynamic CT showed a completely nonenhancing area in the site of the treated tumor in 44 of 45 cases. The remaining patient with metastatic disease had persistent enhancing tissue. Histology showed complete necrosis in four treated tumor nodules and residual viable cancer in one. Twenty-one patients with hepatocellular carcinoma were followed up for 6-19 months (mean, 10 months). Of these patients, six showed recurrences and 15 remained apparently disease-free. Two patients died, one from advanced cancer and one from other causes. Eleven patients with hepatic metastases were followed up for 7-20 months (mean, 12 months). Of these patients, nine showed recurrent disease and only two remained apparently disease-free. Two patients died from disseminated disease. CONCLUSION: RF interstitial thermal ablation of hepatic tumor by expandable needle electrodes is a safe and effective technique. Local ablation of tumors not exceeding 3.5 cm in diameter is achieved in a short time without complications.

Relevance of age on survival of 341 patients with multiple myeloma treated with conventional chemotherapy: updated results of the MM87 prospective randomized protocol. Cooperative Group of Study and Treatment of Multiple Myeloma.

Age could influence the prognosis of multiple myeloma patients treated with conventional chemotherapy. Between January 1987 and March 1990, 341 consecutive previously untreated patients with multiple myeloma received chemotherapy within the prospective, multicentre, randomized Protocol MM87. Survival was evaluated in patients aged > or < or = 66 years (the median age for the whole series) and in a subgroup of patients aged < 55 years. These groups were similar for main clinical characteristics, including results of cytostatic treatment. As of May 1996, 271 (79%) of the 341 patients had died, and median follow-up of the 70 (21%) living patients was 82 months. Overall, younger patients survived longer than older ones. In fact, in patients > and < or = 66 years, median survival was 31 and 44 months (P < 0.00095) and the percentage of patients surviving over 72 months was 17% and 32% (P = 0.0018) respectively; in patients < 55 years, these figures were 57 months and 35% respectively (P = 0.02 and 0.01, with respect to patients aged > 55 years). In all groups, about 50% of the patients surviving over 72 months had stage I disease. For multiple myeloma patients treated with chemotherapy, survival is favourably affected by relatively young age and early stage of disease.

Percutaneous ethanol injection in the treatment of hepatocellular carcinoma. A multicenter survey of evaluation practices and complication rates.

BACKGROUND: Percutaneous ethanol injection (PEI) has become a widely used procedure in the treatment of hepatocellular carcinoma (HCC). However, the criteria for selecting patients are not standardized, and little information is available about the complications of the procedure. METHODS: A questionnaire was sent to 11 experienced Italian centers. It investigated: the size and the number of HCC nodules suitable for treatment and the Child-Pugh risk class of the associated cirrhosis; the performance of the procedure; the number and characteristics of the patients treated; and, finally, any complications. RESULTS: Most of the centers performed PEI in single HCC nodules less than 5 cm in diameter or in multiple nodules if fewer than three, the larger being less than 3 cm. Patients in Child-Pugh's classes A, B, and C with single nodules were generally considered for PEI. A prothrombin time of less than 40% and a platelet count of less than 40,000/mm3 contraindicated PEI in most of the centers. PEI was generally performed on outpatients, using Chiba or spinal needles. One thousand and sixty-six patients (8118 sessions) were enrolled; 74% had a single HCC nodule and 26% multiple nodules. All except four had cirrhosis; 53% were in Child class A, 38% in class B, and 9% in class C. The mean number of sessions needed to destroy an HCC nodule was 6.7 (range, 2-14), with a mean alcohol injection volume of 5.0 ml per session (range, 2-20 ml). One death (0.09%) and 34 complications (3.2%) were reported. Among the complications we call attention to the hemorrhagic ones (eight cases) and tumoral seeding (seven cases). Severe pain experienced during the maneuver led to discontinuation of the procedure in 3.7% of the patients; 13.5% of the patients required analgesics and 24% had fever after PEI. CONCLUSIONS: Some procedural aspects of PEI treatment differ among the various centers a standardization is advisable. In the present survey PEI is a low-risk technique.

Hepatic vascular malformations in hereditary hemorrhagic telangiectasia: Doppler sonographic screening in a large family.

BACKGROUND/AIMS: The prevalence of hepatic vascular malformations in hereditary hemorrhagic telangiectasia has been estimated in the literature on clinical criteria, thus giving unreliable data. In our study the presence of hepatic vascular malformations in hereditary hemorrhagic telangiectasia was evaluated in a large Italian family by using Doppler sonography findings were compared to computed tomography and angiography results. Clinical features were related to the severity of hepatic vascular malformations. METHODS: Seventy-three relatives were checked for the presence of signs of hereditary hemorrhagic telangiectasia. Abdominal Doppler ultrasonography was performed in all of them. Every subject with a positive Doppler ultrasonography for hepatic vascular malformations underwent abdominal computed tomography and celiac angiography. RESULTS: Forty family members proved to be affected by hereditary hemorrhagic telangiectasia. Of these, hepatic vascular malformations were evidenced by Doppler ultrasonography in 13 females. Doppler ultrasongraphy demonstrated minimal hepatic vascular abnormalities in three subjects, moderate in three, and severe in seven. Doppler study was diagnostic for arteriovenous shunt with hepatic veins in seven cases and with portal vein in two. Computed tomography failed to demonstrate hepatic vascular malformations in two cases, while angiography confirmed the Doppler sonographic findings in all cases. Cholestasis was present in subjects with moderate and severe hepatic vascular malformations. CONCLUSIONS: Doppler sonography is the ideal imaging technique to screen hereditary hemorrhagic telangiectasia affected families for hepatic vascular malformations. These malformations do not appear to be age-dependent, but sex-dependent. Cholestasis is the main clinical sign, and it seems to correlate with the severity of hepatic vascular derangement.

Natural history of focal nodular hyperplasia of the liver: an ultrasound study.

Sixteen cases of focal nodular hyperplasia (FNH) of the liver were followed by ultrasound (US) for a mean of 33 months (range 6-81). In 69% of the cases, the diagnosis was incidental. On US the lesions were single in 75% of the cases, localized in the right lobe in 75%, and subcapsular in 50%. No specific US-pattern could be identified. A central scar was found in 19% of the patients. At the end of the follow-up, the size was reduced in 7/16 cases, and in 1/16 the lesion disappeared. The spontaneous reduction of nodules in FNH must be considered in the management of this pseudotumor.

Percutaneous RF interstitial thermal ablation in the treatment of hepatic cancer.

OBJECTIVE: The aim of this study was to evaluate the usefulness of RF interstitial thermal ablation for treating hepatic cancer. SUBJECTS AND METHODS: Fifty patients, 39 who had 41 hepatocellular carcinoma nodules and 11 who had 13 hepatic metastatic nodules, underwent RF interstitial thermal ablation. In all but one, a thermal necrosis volume greater than the tumoral nodule volume was created to obtain total tumor destruction. One large tumor was treated for debulking purposes. RESULTS: Hepatocellular carcinoma nodule destruction was achieved in a mean of 3.3 sessions of RF interstitial thermal ablation. During a mean follow-up of 22.6 months (range, 3-66 months), 16 (41%) of 39 patients had recurrences; two (5%) of these patients showed local recurrences and the remaining 14 (36%) had new lesions. Nine of these 16 patients underwent further RF interstitial thermal ablation that proved effective. RF interstitial thermal ablation was also successfully repeated in four patients who had a second recurrence. With RF interstitial thermal ablation, we treated 54 hepatocellular carcinoma nodules in 39 patients. Eleven (28%) of the 39 patients died: five from hepatic failure due to advanced cancer and six from causes other than cancer. Autopsy was performed on three patients who died from causes other than cancer, one had had two new courses of RF interstitial thermal ablation for two new lesions. Gross examination failed to detect two treated tumor nodules; histologic examination of three other treated tumor nodules showed total necrosis in two nodules and a 3-mm focus of viable cancer cells in the other nodule. Cumulative survival curves showed the median survival time to be 44 months. The survival rate for the first year was 0.94, 0.86 for the second year, 0.68 for the third year, and 0.40 for the fourth and fifth years. In the patients treated for metastatic nodules, posttreatment imaging studies showed necrosis that varied from 80% to 100% in all cases. Pathologic studies performed on two patients who underwent surgery after RF interstitial thermal ablation showed 100% necrosis in one case and 80% necrosis in the other. CONCLUSION: RF interstitial thermal ablation is a useful percutaneous treatment for hepatic cancer.

Clinical presentation, diagnostic work-up and therapeutic choices in two consecutive series of patients with hepatocellular carcinoma.

In two consecutive series of patients with hepatocellular carcinoma (HCC), we compared clinico-laboratory and ultrasonographic characteristics, diagnostic work-up, survival of untreated patients and, finally, therapeutic choices. In addition of the clinical examination, we tested for blood serum alpha-fetoprotein levels, HBsAg and anti-HCV antibodies. Ultrasonography was performed in all the patients. In most cases, a pathologic diagnosis was obtained by ultrasound-guided fine-needle biopsy. As curative treatment we considered open surgery, percutaneous alcohol injection and radio frequency thermal ablation. In the second series, we observed an increased number of patients with compensated cirrhosis and with small HCCs, therefore the number of patients undergoing a potentially curative treatment was higher. The percentage of multiple tumours was comparable in two series implying the presence of two kinds of HCC, different ¿ab initio'. The survival rate of untreated patients was better in the second series.

Experience with poorly myelosuppressive chemotherapy schedules for advanced myeloma. The Cooperative Group of Study and Treatment of Multiple Myeloma.

In a multicentre study, 83 patients with advanced and previously uniformly treated multiple myeloma (MM) were randomised between cyclophosphamide (600 mg m-2) and epirubicin (70 mg m-2), administered every 3 weeks for three courses and both associated with prednisone and interferon-alpha2b. Both regimens were administered on an outpatient basis and had low haematological toxicity. Clinical results were similar. Overall response rate (43%) and median response and survival (5.9 and 14.1 months respectively) compare well with those obtained with more aggressive chemotherapy schedules.

Percutaneous radiofrequency interstitial thermal ablation in the treatment of small hepatocellular carcinoma.

PURPOSE: Very few patients affected by hepatocellular carcinoma can undergo surgery, though it is considered the only curative therapy. We evaluated minimally invasive, percutaneous radiofrequency interstitial thermal ablation for treatment of patients with hepatocellular carcinoma who had no surgical prospects. PATIENTS AND METHODS: Twenty-four patients (16 men and 8 women; age range, 53 to 79 years) with 25 hepatocellular carcinoma nodules of not more than 3.0-cm diameter underwent radiofrequency interstitial thermal ablation treatment with the intent to achieve a cure. In each patient, the thermal necrosis volume achieved was about double the tumor volume. RESULTS: At the end of treatment, destruction of the tumor was achieved in all but two cases in which further thermal lesions were needed. During the mean follow-up interval of 24.8 months (range, 6-64), 13 of 24 patients had recurrences, 9 of whom underwent further radiofrequency thermal ablation treatment. Radiofrequency thermal ablation was again repeated in two patients who showed a second recurrence. A total of 36 hepatocellular carcinoma nodules in 24 patients were treated. No complications were observed. Seven patients died: three due to hepatic failure with advanced cancer, three due to heart failure, and one due to pneumonia. Cumulative survival curves indicated that the median survival time was 44 months and survival rate was 0.95 the first year, 0.84 the second year, 0.67 the third year, and 0.45 the fourth and fifth years. CONCLUSIONS: Percutaneous radiofrequency thermal ablation can be considered a useful new treatment for small hepatocellular carcinoma in patients without surgical prospects. It is simple, effective, and safe, and can be repeated in case of recurrence.

Demonstration and distribution of HCV RNA sequences by in situ hybridization and HCV-related proteins by immunohistochemistry in the liver tissue of patients with chronic HCV infection.

Nonisotopic in situ cytohybridization of HCV RNA was attempted in liver specimens from 12 chronically hepatitis C virus (HCV) infected patients. Oligonucleotides deduced from 5'-noncoding and core regions of the HCV genome were labeled with digoxigenin and used on paraformaldehyde-fixed frozen liver sections. The hybrids were visualized immunohistochemically with alkaline phosphatase-conjugated anti-digoxigenin and alkaline phosphatase substrate. These findings were correlated with the results of tissue immunohistochemistry for HCV antigens identified with specific mouse monoclonal antibodies developed against c22-3 antigen (Ag), a core-encoded protein, and c100-3 Ag, a NS4-encoded protein, and histologic assessment of each liver. HCV RNA detected in the above assay was predominantly cytoplasmic; it was detected in all 12 patients and in none of the controls. Tissue HCV RNA was associated with the presence of cytoplasmic (c100-3 Ag) and membrane (c22-3 Ag) expression of viral proteins in all 9 patients with histological evidence of chronic progressive liver disease as judged by the presence of piecemeal necrosis, and lobular and portal tract inflammation. Despite the presence of abundant HCV RNA, none of 3 patients without histological evidence of chronic liver disease showed intrahepatocyte expression of viral proteins. These findings support the view that tissue HCV antigens are markers of progressive damage and demonstrate that active liver disease does not occur without such markers. It is proposed that synthesis of viral proteins and membrane accumulation of c22-3 Ag may be involved in the pathogenesis of hepatocyte injury in chronic hepatitis C infection.