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.

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.

Diagnostic accuracy of a new tumor serologic marker, CA 19-9: comparison with CEA.

Two hundred and twenty-one hospitalized patients underwent serum determination of CA 19-9, a recently developed tumor marker assay, and CEA. Among these, 53 had a gastrointestinal (GI) cancer, 59 a GI benign disease, 52 a non-GI cancer, and 57 a non-GI benign disease. CA 19-9 assay was more accurate than CEA to detect malignancy, especially of GI source (69.8% sensitivity vs. 24.5% in GI patients); when a cutoff level of 41 ng/ml for CA 19-9 was considered, only 6 false-positive cases were found and both markers showed excellent specificity (94.9% for CEA and 89.9% for CA 19-9 in gastric, hepatobiliary and pancreatic cancer). We conclude that CA 19-9 is a useful GI tumor marker and it seems to be better than CEA in some pathologic situations.

T-cell subsets defined by monoclonal antibodies in monoclonal gammopathy of undetermined significance (MGUS).

Peripheral T lymphocytes from 31 patients with monoclonal gammopathy of undetermined significance (MGUS), and from a group of controls of the same age range, were stained using monoclonal antibodies of the OKT series. The absolute number and the percentage of OKT3+ cells did not differ in patients compared with the controls. The percentage and absolute number of T-cell subsets with helper/inducer OKT4+ and suppressor/cytotoxic OKT8+ phenotype were not different from those of the controls, thus the OKT4/OKT8 ratio in the patients with MGUS was normal (1.60 versus 1.57 in normal controls). These results suggest that MGUS is a B-cell disorder without imbalance of peripheral T-cell subsets unlike B-cell malignancies such as multiple myeloma and B-cell chronic lymphocytic leukemia.

Acute myelocytic leukemia and chronic myelomonocytic leukemia simultaneously with resectable breast cancer: a report of two cases.

This report describes 2 patients who developed acute myelocytic leukemia (AML) type M2 and chronic myelomonocytic leukemia (CMML) of the FAB classification, respectively 2 months and 2 weeks after diagnosis of operable breast cancer. The patient with AML showed pancytopenia 2 months before the diagnosis of AML, had a normal karyotype, and showed a good response to chemotherapy. The patient with CMML had a normal karyotype, and she was treated with hydroxyurea and supportive therapy. The 2 patients had no previous exposure to irradiation or cytotoxic therapy. These cases show that breast cancer and either leukemia or myelodysplastic syndrome may be associated even without previous irradiation or combination chemotherapy.

Value of rapid staining and assessment of ultrasound-guided fine needle aspiration biopsies.

In a series of 160 ultrasonically guided fine needle aspiration (FNA) biopsies, immediate cytologic evaluation of each specimen's adequacy was performed using a rapid staining method. The number of passes was thus limited to what was strictly necessary in order to obtain sufficient material; the average number of passes was only 1.27 per patient. The total series of FNA biopsies had a sensitivity of 95.6%, a specificity of 100% and an overall accuracy of 97.3%. In addition, the cumulative accuracy after each pass was calculated. A significant increase in diagnostic accuracy was found only after the second pass; the third and the fourth passes gave little further improvement. The results indicate that a rapid evaluation of the aspirated material during ultrasound-guided FNA biopsy can reduce the number of punctures needed per case, resulting in less discomfort and, probably, a reduced likelihood of complications for the patient. The results also suggest that a maximum of two punctures will probably yield adequate diagnostic material in most cases.

Simultaneous relapse of liver cell carcinoma and non-Hodgkin's lymphoma in the liver. Report of a case with diagnosis by ultrasonically guided fine needle aspiration biopsy.

A 50-year-old man was diagnosed with non-Hodgkin's lymphoma (NHL) in 1980; he was treated with chemotherapy and achieved complete remission. Six years later he reported upper abdominal pain. Ultrasound (US) showed a 3-cm mass in the right lobe of the liver. Needle aspiration showed hepatocellular carcinoma (HCC). The patient was treated with radical resection of the tumor. Three years later (June 1989), abdominal US showed two lesions in the right lobe of the liver. Needle aspiration and tissue core biopsy showed NHL in one lesion and HCC in the other. The lymphomatous lesion resolved after chemotherapy. The patient died 30 months later (January 1992) from a gastrointestinal hemorrhage; the NHL was in complete remission. This case of the simultaneous presence of HCC and hepatic lymphoma is, to our knowledge, the first diagnosed in vivo.

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.

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.

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.

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 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.

Ultrasonically guided percutaneous drainage of abdominal fluid collections: a long-term study of its therapeutic efficacy.

Fifty patients underwent ultrasonically guided percutaneous drainage (US-GPD) either with needle aspiration or catheter drainage. The procedures resulted in 70% complete recovery, 20% partial success and 10% of failures. The same patients were followed with clinical examination and sonography for a mean time of 36.3 months (minimum follow-up: 12 months). During the follow up period, 10 relapses occurred and one patient, considered for surgery after partial percutaneous treatment of a pyogenic liver abscess, recovered completely under conservative treatment. An analysis of the factors potentially related to the recurrence was made. It was found that one-step needle aspiration of abdominal abscesses and percutaneous treatment of chronic pancreatic pseudocysts are more prone to relapses. We conclude that US-GPD is an efficacious therapy for abdominal fluid collections, but an adequate drainage technique and a careful selection of the patients is crucial to avoid the possibility of relapse.

Vascular signals from pleura-based lung lesions studied with pulsed Doppler ultrasonography.

Vascular signals arising from pleura-based lung lesions were studied in 50 patients using pulsed Doppler ultrasonography. Twenty-seven had malignant lesions and 23 benign lesions. In 24/27 of the malignant masses, we observed no Doppler signals: in 2 cases, a low-velocity, turbulent, pulsatile flow was demonstrated; in 1 case pulsed Doppler ultrasonography showed only a low-velocity, continuous flow. In 20/23 of the benign lesions, we found 2 types of Doppler signal waveforms: an irregularly pulsatile, venous-like signal, and a regularly pulsatile, arterial-like waveform. The last 8 patients of our series underwent color Doppler ultrasound examination, which demonstrated the presence of arterial and venous vessels in 4 benign lesions and the absence of blood flow in 4 malignant masses. To our knowledge, we report for the first time the ability of obtaining Doppler signals from a variety of lung lesions. The actual clinical relevance of this application requires further studies.

Diagnostic aspects and follow-up of 174 cases of hepatocellular carcinoma. Second report.

From June 1981 to June 1989 we diagnosed 174 cases of hepatocellular carcinoma (HCC) at our institution (Piacenza, Northern Italy). Average age was 65.6 years; male to female ratio 3.4. 149 patients were cirrhotic (85.6%); alcohol abuse was present in 88/169 (52.1%); in 53/145 patients all hepatitis B virus markers were negative. Alpha-fetoprotein showed a low diagnostic sensitivity (values above 500 ng only in 49/169 or 29.0%). We used ultrasound (US) examination with a very high identification rate in all cases; pathological diagnosis was achieved by US guided fine-needle aspiration biopsy in 135 patients; in 13, by laparoscopy-histology. Metastases were found in 24/169 cases (14.2%); a second malignancy was diagnosed in 13/169 (7.7%): the most common association was HCC-non-Hodgkin lymphoma. Only 14 patients could be referred to surgery, which significantly improved prognosis.

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.