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Biomedical subjects

S Lazzaroni

Publications and source records attributed to S Lazzaroni.

At least 19 recordsLinked to original sources

WLIP and tolaasin I, lipodepsipeptides from Pseudomonas reactans and Pseudomonas tolaasii, permeabilise model membranes.

The activity of the White Line Inducing Principle (WLIP) and tolaasin I, produced by virulent strains of Pseudomonas reactans and Pseudomonas tolaasii, respectively, was comparatively evaluated on lipid membranes. Both lipodepsipeptides were able to induce the release of calcein from large unilamellar vesicles. Their activity was dependent on the toxin concentration and liposome composition and in particular it increased with the sphingomyelin content of the membrane. Studies of dynamic light scattering suggested a detergent-like activity for WLIP at high concentration (> 27 microM). This effect was not detected for tolaasin I at the concentrations tested (< 28 microM). Differences were also observed in lipodepsipeptides secondary structure. In particular, the conformation of the smaller WLIP changed slightly when it passed from the buffer solution to the lipid environment. On the contrary, we observed a valuable increment in the helical content of tolaasin I which was inserted in the membrane core and oriented parallel to the lipid acyl chains.

Amino Acid Sequence↗

Risk of tumour seeding after percutaneous radiofrequency ablation for hepatocellular carcinoma.

BACKGROUND: A recent small study reported a high rate of neoplastic seeding after cooled-tip radiofrequency ablation (RFA) for hepatocellular carcinoma (HCC) in patients who had undergone previous needle biopsy. Tumour seeding was associated with subcapsular tumour location, poorly differentiated tumours and a high alpha-fetoprotein (AFP) level. The aim of the present study was to determine the rate of neoplastic seeding after RFA in a large series of unselected patients with HCC who had a long follow-up. METHODS: A total of 1314 patients with 2542 nodules were treated in three centres. Median follow-up was 37 months. Needle biopsy had been performed before RFA in 241 patients (18.3 per cent). The influence of subcapsular location, high AFP level and previous biopsy on risk of tumour seeding was assessed. RESULTS: Neoplastic seeding was identified in 12 patients (0.9 per cent); the rate was comparable at the three centres (0.9, 0.7 and 1.4 per cent). Only previous biopsy was significantly associated with tumour seeding (P = 0.004). CONCLUSION: RFA with a cooled-tip needle was associated with a low risk of neoplastic seeding, even in unselected patients. The use of biopsy before RFA is to be discouraged, particularly when liver transplantation is a possibility at a later date.

Carcinoma, Hepatocellular↗

Percutaneous ethanol injection: single session treatment.

OBJECTIVE: Percutaneous ethanol injection (PEI) has become one of the most widely used procedures for treating hepatocellular carcinoma (HCC) in patients with cirrhosis. PEI spread rapidly thanks to its ease of execution, safety, low resection cost, repeatability, therapeutic efficacy, and survival rates comparable to those of surgical resection. A new version of the procedure known as "single session" PEI, designed for treatment of large HCC under general anesthesia, was proposed in 1993. MATERIALS AND METHODS: In our study of 108 patients with HCC>5 cm in diameter, 24 patients (Group A), were treated for a single and encapsulated lesions measuring from 5-8.5 cm, 63 patients (Group B), had a single and infiltrating lesions measuring from 5-10 cm or multiple HCC; and 21 patients (Group C), had advanced disease. RESULTS: In Group A, complete necrosis was achieved in 58.3% of lesions, in Group B complete necrosis was achieved only in encapsulated lesions. In infiltrating lesions of Group B and C, complete necrosis was never obtained. Survival of patients at 3 years with encapsulated HCC was 57%, in infiltrating or multiple HCC 42%, and in advanced HCC 0%. One death due to bleeding of esophageal varices occurred in a Child's C patient. Major complications included intraperitoneal hemorrhage, an important hepatic decompensation, a transitory renal insufficiency, and two infarction of adiacent segment. CONCLUSION: Single session PEI is as effective in inducing liver tumor necrosis as traditional PEI. Its advantage are shorter treatment time and the capability of treating larger and multiple HCC. The One-shot technique proved a more aggressive therapeutic modality than traditional PEI.

Carcinoma, Hepatocellular↗

Radiofrequency thermal ablation of hepatocellular carcinoma.

Radiofrequency (RF) ablation resulted in a higher complete necrosis than percutaneous ethanol injection (PEI), above all in infiltrating lesions, and requires fewer treatment sessions in the treatment of small size tumors. We achieved 90% of complete necrosis in hepatocellular carcinoma (HCC)<3 cm, 71% in medium (3-5 cm) and 45% in large (5.1-9 cm) HCC. However, near complete necrosis was obtained in the majority of the remaining tumors. PEI is preferable in lesions at risk with RF, i.e. adjacent to main biliary ducts or to intestinal loops. Our current 3-yr survival in child A patient with single HCC<5 cm is 85%.

Animals↗

Purification and characterization of novel antifungal compounds from the sourdough Lactobacillus plantarum strain 21B.

Sourdough lactic acid bacteria were selected for antifungal activity by a conidial germination assay. The 10-fold-concentrated culture filtrate of Lactobacillus plantarum 21B grown in wheat flour hydrolysate almost completely inhibited Eurotium repens IBT18000, Eurotium rubrum FTDC3228, Penicillium corylophilum IBT6978, Penicillium roqueforti IBT18687, Penicillium expansum IDM/FS2, Endomyces fibuliger IBT605 and IDM3812, Aspergillus niger FTDC3227 and IDM1, Aspergillus flavus FTDC3226, Monilia sitophila IDM/FS5, and Fusarium graminearum IDM623. The nonconcentrated culture filtrate of L. plantarum 21B grown in whole wheat flour hydrolysate had similar inhibitory activity. The activity was fungicidal. Calcium propionate at 3 mg ml(-1) was not effective under the same assay conditions, while sodium benzoate caused inhibition similar to L. plantarum 21B. After extraction with ethyl acetate, preparative silica gel thin-layer chromatography, and chromatographic and spectroscopic analyses, novel antifungal compounds such as phenyllactic and 4-hydroxy-phenyllactic acids were identified in the culture filtrate of L. plantarum 21B. Phenyllactic acid was contained at the highest concentration in the bacterial culture filtrate and had the highest activity. It inhibited all the fungi tested at a concentration of 50 mg ml(-1) except for P. roqueforti IBT18687 and P. corylophilum IBT6978 (inhibitory concentration, 166 mg ml(-1)). L. plantarum 20B, which showed high antimold activity, was also selected. Preliminary studies showed that phenyllactic and 4-hydroxy-phenyllactic acids were also contained in the bacterial culture filtrate of strain 20B. Growth of A. niger FTDC3227 occurred after 2 days in breads started with Saccharomyces cerevisiae 141 alone or with S. cerevisiae and Lactobacillus brevis 1D, an unselected but acidifying lactic acid bacterium, while the onset of fungal growth was delayed for 7 days in bread started with S. cerevisiae and selected L. plantarum 21B.

Antifungal Agents↗

Hepatocellular carcinoma: radio-frequency ablation of medium and large lesions.

PURPOSE: To study local therapeutic efficacy, side effects, and complications of radio-frequency (RF) ablation in the treatment of medium and large hepatocellular carcinoma (HCC) lesions in patients with cirrhosis or chronic hepatitis. MATERIALS AND METHODS: One-hundred fourteen patients who were under conscious sedation or general anesthesia had 126 HCCs greater than 3.0 cm in diameter treated with RF by using an internally cooled electrode. Eighty tumors were medium (3.1-5.0 cm), and 46 were large (5.1-9.5 cm). The mean diameter for all tumors was 5.4 cm. At imaging, 75 tumors were considered noninfiltrating, and 51 were considered infiltrating. RESULTS: Complete necrosis was attained in 60 lesions (47.6%), nearly complete (90%-99%) necrosis in 40 lesions (31.7%), and partial (50%-89%) necrosis in the remaining 26 lesions (20.6%). Medium and/or noninfiltrating tumors were treated successfully significantly more often than large and/or infiltrating tumors. Two major complications (death, hemorrhage requiring laparotomy) and five minor complications (self-limited hemorrhage, persistent pain) were observed. The single death was due to a break in sterile technique rather than to the RF procedure itself. CONCLUSION: RF ablation appears to be an effective, safe, and relatively simple procedure for the treatment of medium and large HCCs.

Aged↗

Antioxidant drugs combined with alpha-interferon in chronic hepatitis C not responsive to alpha-interferon alone: a randomized, multicentre study.

OBJECTIVE: After non-response to the initial course of therapy, retreatment with alpha-interferon is not effective. The aim of this study was to ascertain whether the administration of N-acetyl cysteine and vitamin E could increase the response rate to retreatment with alpha-interferon. DESIGN: Prospective, multicentre clinical trial. SETTING: Twelve hospitals in Lombardy, Italy. PARTICIPANTS: 120 consecutive patients affected by biopsy-proven chronic hepatitis C who had been non-responders to a previous course of alpha-interferon, administered at the dosage of 3-6 million units (MU) three times a week (tiw) for 6 months. INTERVENTIONS: The patients were randomly assigned to one of two groups of treatment: group A, natural interferon-alphaN3, 6 or 9 MU tiw, when the body weight was < 60 kg or > or = 60 kg, respectively; group B, the same dosage of natural interferon-alphaN3 in association with oral administration of N-acetyl cysteine 1200 mg/day and vitamin E 600 mg/day. The period of treatment was 6 months in both groups. RESULTS: Neither end-therapy biochemical response nor sustained biochemical response rates were improved by the combination treatment, and in no case was clearance of the virus from serum observed. CONCLUSIONS: In this randomized study carried out on 120 patients with chronic hepatitis C not responsive to alpha-interferon, oral supplementation with N-acetyl cysteine and vitamin E did not improve the poor efficacy of retreatment with alpha-interferon alone.

Acetylcysteine↗

Small hepatocellular carcinoma: treatment with radio-frequency ablation versus ethanol injection.

PURPOSE: To compare the effectiveness of radio-frequency (RF) ablation with that of percutaneous ethanol injection in the treatment of small hepatocellular carcinoma (HCC). MATERIALS AND METHODS: Eighty-six patients with 112 small (< or = 3-cm-diameter) HCCs underwent RF ablation (42 patients with 52 tumors) or percutaneous ethanol injection (44 patients with 60 tumors). Therapeutic efficacy was evaluated with dual-phase spiral computed tomography performed at least 4 months after treatment. RESULTS: Complete necrosis was achieved in 47 of 52 tumors with RF ablation (90%) and in 48 of 60 tumors with percutaneous ethanol injection (80%). These results were obtained with an average of 1.2 sessions per tumor with RF ablation and 4.8 sessions per tumor with percutaneous ethanol injection. One major complication (hemothorax that required drainage) and four minor complications (intraperitoneal bleeding, hemobilia, pleural effusion, cholecystitis) occurred in patients treated with RF ablation; no complications occurred in patients treated with percutaneous ethanol injection. CONCLUSION: RF ablation results in a higher rate of complete necrosis and requires fewer treatment sessions than percutaneous ethanol injection. However, the complication rate is higher with RF ablation than with percutaneous ethanol injection. RF ablation is the treatment of choice for most patients with HCC.

Aged↗

Long term results of single session percutaneous ethanol injection in patients with large hepatocellular carcinoma.

BACKGROUND: The objective of this study was to evaluate the indications for percutaneous ethanol injection (PEI) performed in a single session under general anesthesia for treating patients with cirrhosis and large (tumors > 5 cm) hepatocellular carcinoma (HCC), and relevant survival curves. METHODS: Between November 1991 and November 1996, 108 patients were treated (a total of 128 procedures). They fell into 3 groups: 24 patients with single, encapsulated HCC measuring from 5-8.5 cm (Group A); 63 patients with single, infiltrating HCC measuring from 5-10 cm or multiple HCC (Group B); and 21 patients with advanced disease, either hepatic (Child's Class C) or neoplastic (symptomatic HCC or with portal thrombosis) type (Group C). The mean amount of ethanol injected was 62 mL. The average hospital stay was 3.8 days. The mean follow-up time was 40 months. RESULTS: The 1-, 2-, 3-, and 4-year survival rates were: 72%, 65%, 57%, and 44%, respectively, for Group A; 73%, 60%, 42%, and 18%, respectively, for Group B; and 46%, 25%, and 0%, respectively, for Group C. Mortality was 0.7% (bleeding from esophageal varices in a Child's Class C patient). The rate of major complications was 4.6% (1 case of peritoneal hemorrhage, 1 case of severe liver failure, 1 case of transient renal insufficiency, 1 case of peritoneal seeding, and 2 cases of infarctions of a segment adjacent to the tumor). CONCLUSIONS: Single session PEI has been proven to be a valid alternative in patients otherwise treated surgically or with transcatheter arterial chemoembolization who present with adverse prognostic factors or risks for these therapies, and may be an option for selected patients with advanced disease previously excluded from any therapy. Risk conditions are marked portal or pulmonary hypertension or esophageal varices at risk of bleeding, superficial tumors with severe coagulation disorders, hyperfibrinolysis, chronic renal insufficiency, and obstructive jaundice.

Administration, Cutaneous↗

Saline-enhanced radio-frequency tissue ablation in the treatment of liver metastases.

PURPOSE: To assess the effect of intraparenchymal saline injection on the results of radio-frequency (RF) tissue ablation. MATERIALS AND METHODS: Ex vivo and in vivo animal RF ablation was performed with and without intraparenchymal saline injection. Initially, saline was injected as a bolus (1-20 mL) before RF application. For subsequent in vivo studies, saline was injected as a bolus before RF application or continuously (1 mL/min) during RF application. Finally, 14 patients with liver metastases and one patient with primary cholangiocarcinoma were treated with the continuous infusion technique. A single RF electrode (tip exposure, 1-3 cm) was used with various ablation parameters. RESULTS: With pretreatment bolus injection of saline, lesions measured 1.4 cm +/- 0.1, 1.6 cm +/- 0.2, and 1.2 cm +/- 0.1 in ex vivo liver, in vivo animal muscle, and in vivo animal liver, respectively. Without saline enhancement, lesion sizes were 1.0 +/- 0.2, 1.2 +/- 0.2, and 0.8 +/- 0.1 cm, respectively. With continuous saline injection in in vivo pig liver, lesion size was 1.8 - 4.1 cm in diameter. In human tumors, necrosis volume was variable, but complete necrosis was seen in 13 of 25 lesions (diameter, 1.2-3.9 cm). Partial necrosis greater than 50% was seen in 12 lesions (diameter, 1.5-4.5 cm). CONCLUSION: Saline-enhanced RF ablation might permit percutaneous destruction of large liver lesions.

Adult↗

Hepatocellular carcinoma and cirrhosis in 746 patients: long-term results of percutaneous ethanol injection.

PURPOSE: To define indications for percutaneous ethanol injection (PEI) in patients with hepatocellular carcinoma (HCC) and cirrhosis. MATERIALS AND METHODS: Survival rates were determined in 746 patients who had undergone PEI (567 men, 179 women; mean age, 64.3 years; mean follow-up, 36 months). RESULTS: In patients with Child A (n = 293), B (n = 149), or C (n = 20) cirrhosis and single HCCs 5 cm or smaller, the 3-5 year survival rate was 47%-79%, 29%-63%, and 0%-12%, respectively. In patients with Child A cirrhosis, it was 36%-68% for multiple HCCs (n = 121), 30%-53% for single HCCs larger than 5 cm (n = 28), and 0%-16% for advanced HCC (n = 16). Treatment was associated with a 1.7% rate of severe complications and a 0.1% mortality rate. CONCLUSION: PEI proved safe, effective, and repeatable and had a low cost. Survival after PEI was comparable to that after surgery, probably because of a balancing between greater radicality of surgery and absence of early mortality and liver damage of PEI.

Administration, Cutaneous↗

Percutaneous ethanol injection of hepatic tumors: single-session therapy with general anesthesia.

OBJECTIVE: We studied the feasibility and the effectiveness of percutaneous ethanol injection, performed with general anesthesia in a single session, for treating malignant hepatic lesions. SUBJECTS AND METHODS: We treated 30 patients with sonographically guided percutaneous injection of ethanol. Twenty had hepatocellular carcinoma and cirrhosis, and 10 had hepatic metastases, principally from colon cancer. The mean volume of ethanol injected was 57 ml (range, 6-165 ml). RESULTS: CT showed complete necrosis (up to 8.2 cm) in seven of 10 patients with encapsulated hepatocellular carcinoma and about 90% necrosis in the remaining three patients. In four of these patients, the alpha-fetoprotein level fell from more than 200 ng/ml to less than 20 ng/ml during treatment. In 10 patients with infiltrating hepatocellular carcinoma, about 70-90% necrosis was achieved; in six of these patients, the alpha-fetoprotein level, which had been more than 200 ng/ml, decreased during treatment. In the 10 patients with metastases, more than 50% necrosis was always achieved. Levels of carcinoembryonic antigen decreased after treatment in all patients. In three patients who had cirrhosis with superficial hepatocellular carcinoma, peritoneal hemorrhage occurred but did not require transfusion. CONCLUSION: Our results show that percutaneous injection of ethanol in a single session with general anesthesia is feasible and effective and has several advantages over multisession therapy. These include shorter treatment time and the ability to treat larger and more numerous lesions.

Adult↗

Percutaneous ethanol injection in the treatment of hepatocellular carcinoma in cirrhosis. A study on 207 patients.

In 207 cirrhotic patient carriers of hepatocellular carcinoma (HCC), percutaneous ethanol injection (PEI) was administered with ultrasound guidance. The patients were classified as Child's Class A, 136; B, 54; and C, 17. Their mean age was 63.5 years, and the male-female ratio was 3.5:1. There was a single HCC less than 5 cm in diameter in 162 patients; 45 had more than one HCC. The follow-up ranged from 5 to 71 months (mean, 25 months). No noteworthy complications occurred during or after 2485 treatments. The 1-year, 2-year, and 3-year survival percentages (by the Kaplan-Meier method) for the patients with one HCC were 90%, 80%, and 63%, respectively. The corresponding percentages by Child's class were 97%, 92%, and 76% for Class A; 88%, 68%, and 42% for B; and 40%, 0%, and 0% for C. The 1-year, 2-year and 3-year survival rates for patients with more than one HCC were 90%, 67%, and 31% respectively. These results were similar to those found by others and showed that PEI was a safe, reproducible, easy-to-do, and low-cost therapeutic technique. In terms of survival, these PEI results were better than the published results of no treatment and equivalent to those of surgery. In uncontrolled series, bias can play an important role. Therefore, additional trials would be useful.

Aged↗

Liver metastases: results of percutaneous ethanol injection in 14 patients.

Percutaneous ethanol injection (PEI) was performed under ultrasound (US) guidance in the outpatient department in 14 patients with 21 metastases 1.0-3.8 cm in diameter. The primary cancer was colorectal adenocarcinoma (seven patients), adenocarcinoma of the stomach (four patients), abdominal leiomyosarcoma (one patient), gastrinoma of unknown origin (one patient), and bronchial carcinoid (one patient). The indicators of therapeutic efficacy were US, computed tomography, fine-needle biopsy, and serologic markers. No complications occurred after a total of 175 treatment sessions. Complete response was obtained in 11 lesions, nine of which were less than 2 cm in diameter, and in all endocrine metastases (four lesions in two patients) with a maximum, recurrence-free follow-up of 38 months. Carcinoembryonic antigen values decreased in all patients but one for a 2-6-month period. The natural course of metastatic disease strictly limits the applicability of PEI, a local treatment. Single, metachronous, nonoperable metastasis of adenocarcinoma and endocrine metastases seem to be the only indications for PEI.

Adolescent↗

Intralesional ethanol in the treatment of unresectable liver cancer.

Percutaneous ethanol injection (PEI) under ultrasonography guidance has been widely tried in not advanced hepatocellular carcinoma (HCC). Ten years after the introduction of PEI, some conclusions of its indications can be drawn. In our series, 210 cirrhotic patients were treated; 141 with multisession PEI in an outpatient clinic, 57 with "single session" PEI under general anesthesia, and 12 with both. The 1-, 3-, and 5-year survival rates (by Kaplan-Meier method) were 953%, 65%, and 41% for Child class A patients with single HCC < or = 5 cm, and 88%, 47%, and 33% for patients with multiple HCC up to five lesions < or = 5 cm. In these patients the local recurrence rate was 15% and the new lesion rate at the 5-year follow-up was 74%. One death due to hemorrhage from esophageal varices in a Child class C patient treated by single session PEI occurred. The large number of cirrhotic patients demand for effective, safe, repeatable, low-cost treatment that can be offered at many centers. PEI meets all these requirements. PEI is proposed as the treatment of choice for the mentioned patients, excluding candidates for liver transplantation and surgical resection according to the predictive adverse factors currently in use. "Single session" technique widened the indications of traditional PEI to larger lesions.

Aged↗