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Biomedical subjects

F Izzo

Publications and source records attributed to F Izzo.

At least 37 records · Page 2Linked to original sources
PubMed1999

Soluble interleukin-2 receptor levels in hepatocellular cancer: a more sensitive marker than alfa fetoprotein.

BACKGROUND: Worldwide, the majority of cases of hepatocellular cancer (HCC) arise in individuals with chronic hepatitis B or C virus infections. Early detection of HCC in these patients provides the best chance for curative treatment, but serum alfa fetoprotein (AFP) levels are frequently normal in patients with small HCCs. The purpose of this study was to determine: (1) whether soluble interleukin-2 receptor (sIL-2R) levels are elevated more frequently than AFP levels in HCC patients and (2) whether sIL-2R levels are useful as a marker of successful treatment and recurrence of disease. PATIENTS AND METHODS: We are performing a prospective screening program with high-risk, chronic hepatitis virus-infected patients to detect HCC. Patients are screened by using abdominal ultrasonography, serum AFP measurements, and serum sIL-2R measurements. Normal serum sIL-2R levels were established using results from 174 healthy volunteers with no evidence of hepatitis virus infection or HCC. RESULTS: HCC has been diagnosed in 99 patients from a cohort of 1520 screened patients. Serum AFP levels were elevated in 79 patients (80%), whereas sIL-2R levels were elevated in 98 of the 99 patients (99%, P < .01, chi2 test). For 27 of the 99 patients (27%), HCC was diagnosed at an early stage and complete resection or ablation was performed. Serum sIL-2R levels returned to normal in all 27 patients after treatment, whereas AFP levels remained slightly elevated in 5 of the 27 (18%). Among the 16 patients in this group of 27 who developed recurrent HCC, sIL-2R levels became elevated in all 16, whereas AFP levels were elevated at diagnosis of recurrence for only 10 (P < .05). CONCLUSIONS: This study with chronic hepatitis B or C virus-infected patients indicates that (1) serum sIL-2R levels are abnormal in patients with HCC with a significantly greater frequency, compared with AFP levels, and (2) sIL-2R levels are a more sensitive marker of successful treatment and recurrence of HCC. Based on these findings, we now use serum sIL-2R measurements both to screen high-risk patients and to monitor treatment responses in patients with hepatitis who develop HCC.

Adult↗
PubMed1999

Intraoperative radiofrequency ablation or cryoablation for hepatic malignancies.

BACKGROUND: The majority of patients with primary or metastatic malignancies confined to the liver are not candidates for resection because of tumor size, location, multifocality, or inadequate functional hepatic reserve. Cryoablation has become a common treatment in select groups of these patients with unresectable liver tumors. However, hepatic cryoablation is associated with significant morbidity. Radiofrequency ablation (RFA) is a technique that destroys liver tumors in situ by localized application of heat to produce coagulative necrosis. In this study, we compared the complication and early local recurrence rates in patients with unresectable malignant liver tumors treated with either cryoablation or RFA. PATIENTS AND METHODS: Patients with hepatic malignancies were entered into two consecutive prospective, nonrandomized trials. The liver tumors were treated intraoperatively with cryoablation or RFA; intraoperative ultrasonography was used to guide placement of cryoprobes or RFA needles. All patients were followed up postoperatively to assess complications, treatment response, and local recurrence of malignant disease. RESULTS: Cryoablation was performed on 88 tumors in 54 patients, and RFA was used to treat 138 tumors in 92 patients. Treatment-related complications, including 1 postoperative death, occurred in 22 of the 54 patients treated with cryoablation (40.7% complication rate). In contrast, there were no treatment-related deaths and only 3 complications after RFA (3.3% complication rate, P<0.001). With a median follow-up of 15 months in both patient groups, tumor has recurred in 3 of 138 lesions treated with RFA (2.2%), versus 12 of 88 tumors treated with cryoablation (13.6%, P<0.01). CONCLUSIONS: RFA is a safe, well-tolerated treatment for patients with unresectable hepatic malignancies. This study indicates that (1) complications occur much less frequently following RFA of liver tumors compared with cryoablation of liver tumors, and (2) early local tumor recurrence is infrequent following RFA.

Algorithms↗
PubMed1999

Radiofrequency ablation of unresectable primary and metastatic hepatic malignancies: results in 123 patients.

OBJECTIVE: To describe the safety and efficacy of radiofrequency ablation (RFA) to treat unresectable malignant hepatic tumors in 123 patients. BACKGROUND: The majority of patients with primary or metastatic malignancies confined to the liver are not candidates for resection because of tumor size, location, or multifocality or inadequate functional hepatic reserve. Local application of heat is tumoricidal; therefore, the authors investigated a novel RFA system to treat patients with unresectable hepatic cancer. PATIENTS AND METHODS: Patients with hepatic malignancies were entered into a prospective, nonrandomized trial. The liver tumors were treated percutaneously or during surgery under ultrasound guidance using a novel LeVeen monopolar array needle electrode and an RF 2000 generator. All patients were followed to assess complications, treatment response, and recurrence of malignant disease. RESULTS: RFA was used to treat 169 tumors (median diameter 3.4 cm, range 0.5 to 12 cm) in 123 patients. Primary liver cancer was treated in 48 patients (39.1%), and metastatic liver tumors were treated in 75 patients (60.9%). Percutaneous and intraoperative RFA was performed in 31 patients (35.2%) and 92 patients (74.8%), respectively. There were no treatment-related deaths, and the complication rate after RFA was 2.4%. All treated tumors were completely necrotic on imaging studies after completion of RFA treatments. With a median follow-up of 15 months, tumor has recurred in 3 of 169 treated lesions (1.8%), but metastatic disease has developed at other sites in 34 patients (27.6%). CONCLUSIONS: RFA is a safe, well-tolerated, and effective treatment to achieve tumor destruction in patients with unresectable hepatic malignancies. Because patients are at risk for the development of new metastatic disease after RFA, multimodality treatment approaches that include RFA should be investigated.

Adult↗
PubMed1998

Outcome of 67 patients with hepatocellular cancer detected during screening of 1125 patients with chronic hepatitis.

OBJECTIVE: We performed this prospective screening trial in chronic hepatitis virus-infected patients to determine the incidence of hepatocellular cancer (HCC) and the resectability and long-term survival rates of these HCC patients. SUMMARY BACKGROUND DATA: Chronic hepatitis B or C virus infection is a major etiologic factor in human HCC. It is not clear if routine screening of chronic viral hepatitis patients improves the survival of patients who develop HCC. METHODS: Screening for HCC was offered to patients chronically seropositive (>5 years) for hepatitis B or C infection. All patients underwent percutaneous core liver biopsy to assess the histologic severity of chronic liver injury. Patients were screened initially and every 3 months thereafter with serum alpha-fetoprotein and transabdominal ultrasound evaluations; HCC was confirmed by needle biopsy of liver tumors. RESULTS: Screening was performed on 1125 hepatitis-positive patients (804 with hepatitis C, 290 with hepatitis B, 31 with both). On liver biopsy, 800 patients had mild chronic active hepatitis and 325 had severe chronic active hepatitis, cirrhosis, or both. Initial screening detected HCC in 61 patients. HCC was detected in six more patients during follow-up; thus, the incidence of HCC was 5.9% (67/1125). However, 66 of the 67 HCC cases (98.5%) arose in the 325 patients with severe chronic active hepatitis or cirrhosis (66/325 [20.3%] vs. 1/800 [0.1%], p < 0.0001 [Wilcoxon signed rank]). Median follow-up of the 67 HCC patients was 24 months. Locally advanced or metastatic, unresectable HCC occurred in 43 patients (64.2%); 24 patients (35.8%), including the 6 patients detected during follow-up screening, underwent margin-negative resection. The median survival for the 24 resected patients was 26 months, compared to 6 months for the 43 patients with unresectable cancer (p < 0.0001, Wilcoxon signed rank). CONCLUSIONS: HCC was found to arise in 20.3% of patients with chronic hepatitis B or C infection and severe liver injury. Initial screening detected resectable lesions in less than half the HCC patients. Routine screening of chronic hepatitis B or C virus-infected patients with ultrasound and alpha-fetoprotein determination should be reserved for patients with severe chronic active hepatitis, cirrhosis, or both.

Adult↗
PubMed1997

Activation of human Kupffer cells by thymostimulin (TP-1) to produce cytotoxicity against human hepatocellular cancer.

BACKGROUND: In a small pilot study, thymostimulin (TP-1) produced tumor regression in almost 50% of patients with hepatocellular cancer (HCC) who were treated with TP-1 alone. However, the mechanism of the TP-1-mediated antitumor effect against HCC is unknown. METHODS: Human hepatocytes and Kupffer cells were isolated from liver biopsy specimens by collagenase infusion and counterflow elutriation. Hepatocytes and Kupffer cells were incubated in vitro with clinically relevant doses of TP-1. Cell-free supernatant levels for a panel of growth factors and monokines were determined by enzyme-linked immunosorbent assay. The cytotoxic activity of TP-1 alone of TP-1-stimulated hepatocyte and Kupffer cell supernatants against Hep G2 and Hep 3B human HCC cells in vitro was measured by MIT assay. RESULTS: Doses of TP-1 up to 100 micrograms/ml produced no cytotoxicity against Hep G2 or Hep 3B cells. Furthermore, supernatants from TP-1-treated hepatocytes produced no cytotoxicity against Hep G2 or Hep 3B cells, and TP-1 did not stimulate the release of transforming growth factor (TGF)-alpha, TGF-beta, or hepatocyte growth factor. TP-1-treated Kupffer cell supernatants produced significant cytotoxicity against Hep G2 cells but produced no cytotoxicity against Hep 3B cells. Kupffer cells stimulated by TP-1 released significant amounts of tumor necrosis factor-alpha (TNF-alpha), interleukin (IL)-1 alpha, and IL-6 compared with control Kupffer cells (p < 0.01). The activity of TP-1-treated Kupffer cell supernatants against Hep G2 cells was blocked by anti-TNF-alpha antibodies, whereas neither anti-IL-1 alpha nor anti-IL-6 antibodies blocked cytotoxicity. CONCLUSIONS: These results demonstrate that TP-1 cytotoxicity against human HCC cells is not mediated directly or through hepatocytes, but occurs through activation of Kupffer cells and release of TNF-alpha. Understanding the mechanism of TP-1 cytotoxicity against human HCC has been used to plan a phase 1 trial of TP-1 combined with regional infusion of doxorubicin to treat unresectable HCC.

Adjuvants, Immunologic↗
PubMed1997

Laparoscopically guided bipolar radiofrequency ablation of areas of porcine liver.

BACKGROUND: Bipolar radiofrequency ablation (BRFA) is a promising technique with which to treat unresectable primary and metastatic liver tumors. Its effects on normal liver tissue and postoperative liver function, however, are unknown. We performed this study to determine (1) the feasibility of using laparoscopic ultrasound to guide placement of BRFA needle electrodes in the liver and (2) the histopathologic, hepatic biochemical, and systemic hemodynamic responses to BRFA. METHODS: Two BRFA lesions were created in the liver of adult domestic pigs to ablate 8-10% of the normal liver volume. Laparoscopic ultrasound was used to guide creation of one peripheral liver lesion and one central liver lesion (with a major hepatic or portal venous vein branch in the center of the BRFA lesions) in each animal. BRFA of liver tissue was performed by passing 12 W of RF power for 16 min across two 16-gauge active-needle electrodes placed 3 cm apart. RESULTS: All animals survived the procedure without significant hemodynamic alterations during or after BRFA. All animals had a transient elevation in serum transaminase levels that returned to normal within 1 week of the BRFA of liver tissue. Gross and microscopic histopathology of the BRFA lesions revealed 2.0-2.5-cm zones of complete coagulative necrosis around and between the BRFA needle tracks without destruction of major blood vessel walls. CONCLUSIONS: This study demonstrates (1) that laparoscopic ultrasound can be used to guide placement of BRFA needles in the liver and (2) that BRFA produces focal destruction of liver without significant systemic hemodynamic responses or alterations in liver function. Further studies of this technique to ablate malignant liver tumors are ongoing.

Animals↗
PubMed1996

Alternating floxuridine and 5-fluorouracil hepatic arterial chemotherapy for colorectal liver metastases minimizes biliary toxicity.

BACKGROUND: The goals of this study of a hepatic arterial infusion (HAI) regimen of alternating floxuridine and 5-fluorouracil were to evaluate the treatment-related toxic effects, the antitumor response rate, and patient survival. METHODS: Fifty-seven consecutive patients were treated with implanted HAI pumps and received a regimen of alternating floxuridine (0.1 mg/kg/day continuous HAI for 7 days) followed by a weekly HAI pump bolus of 5-fluorouracil (15 mg/kg for 3 weeks). Any changes in treatment plan because of toxicity, antitumor response, and survival were recorded. RESULTS: Thirty-one (54.4%) patients responded to this HAI regimen; 14 (24.5% )patients had stable disease, and 12 (21.1%) progressed during treatment. Responders or patients with stable disease had a significantly (P < 0.05) improved survival rate (19 months median) compared with patients in whom disease progressed (12 months median). Two (3.5%) patients developed biliary sclerosis and 12 (21.1%) had mild transient liver function abnormalities. The liver alone or in combination with another area was the site of first progression of disease in 40 (70.2%) patients. CONCLUSIONS: This regimen had reversible or no hepatobiliary toxicity in more than 95% of patients. Tumor reduction or stabilization of disease was observed in 79% of the patients, who had a median survival of 19 months. Reduced toxicity and more effective chemotherapeutic regimens may increase the likelihood of survival after HAI chemotherapy for unresectable colorectal liver metastases.

Adult↗
PubMed1996

Correlation of soluble interleukin-2 receptor levels with severity of chronic hepatitis C virus liver injury and development of hepatocellular cancer.

BACKGROUND: Patients with acute and chronic hepatitis B virus infection have elevated serum levels of soluble interleukin-2 receptor. This study examined patients with chronic hepatitis C virus infection to determine whether serum soluble interleukin-2 receptor levels were elevated and whether the degree of these elevations in serum levels correlated with histologic severity of hepatitis-related liver injury. METHODS: Percutaneous liver biopsies were performed on 123 patients with chronic hepatitis C virus infection. Serum levels of soluble interleukin-2 receptor in these 123 patients were measured by means of specific enzyme-linked immunoassay and were compared with levels in 174 subjects in a hepatitis-free control group. RESULTS: Soluble interleukin-2 receptor levels were significantly higher in the patients with hepatitis C than in subjects in a control group (p < 0.0001). A progressive and significant increase occurred in soluble interleukin-2 receptor levels with increasing severity of liver injury (p < 0.001). The highest levels of soluble interleukin-2 receptor occurred in patients who had hepatocellular cancer. CONCLUSIONS: Soluble interleukin-2 receptor levels correlate with the histologic severity of liver damage in patients with chronic hepatitis C virus infection and may be useful as a marker in patients at high risk of getting hepatocellular cancer.

Adolescent↗
PubMed1996

Survival factors in 186 patients younger than 40 years old with colorectal adenocarcinoma.

BACKGROUND: We sought to determine the clinical factors and tumor characteristics associated with the reported poor prognosis in young patients with carcinoma of the colon and rectum. STUDY DESIGN: A retrospective review was performed of 186 patients younger than 40 years of age who were treated for primary colorectal adenocarcinoma. The median age was 34.3 years, and the median follow-up period was 9.4 years. Clinical and tumor histopathologic parameters were analyzed. RESULTS: Regional lymph node metastases, distant metastases, or both, were seen at first examination in 65.6 percent of young patients. Histopathologic indicators of more aggressive tumor biology were present at a significantly higher frequency in young patients compared with patients older than 40 years (p < 0.001). Poorly differentiated tumor grade was present in 41.0 percent, signet-ring cell tumors were found in 11.1 percent, and infiltrating tumor leading edges were present in 69.0 percent of young patients. Among young patients with stage II disease, vascular invasion was a significant negative prognostic variable (p < 0.05). CONCLUSIONS: We have demonstrated an increased incidence of three biological indicators of aggressive and potentially metastatic tumor biology in 186 young patients with carcinoma of the colon and rectum: signet-ring cell carcinoma, infiltrating tumor edges, and aggressive histologic grade in the primary adenocarcinoma. The increased incidence of these three histologic measures of more aggressive carcinoma of the colon and rectum in part accounts for the higher rate of advanced disease at presentation in patients younger than 40.

Adenocarcinoma↗
PubMed1995

Collagen matrix cisplatin prevents local tumor growth after margin-positive resection.

The extent of a tumor, sometimes combined with its anatomic location, can compromise the surgeon's ability to obtain clear margins of resection. Regional recurrence of a tumor in the resection bed frequently produces significant local morbidity and limits patient survival time and quality of life. A positive margin resection model was created by induction of perinephric VX-2 tumors in New Zealand white rabbits followed by unilateral nephrectomy with grossly positive margins in the retroperitoneum. Resection bed injection of a novel collagen matrix with cisplatin (CDDP) and epinephrine prevented tumor recurrence in all treated animals. In contrast, control animals treated with CDDP alone, CDDP and epinephrine alone, or the collagen matrix with epinephrine had bulky tumor recurrence in the resection bed. Resection bed tissue levels of platinum were determined by flameless absorption spectrophotometry at 1, 4, and 7 days following nephrectomy and injection of the collagen matrix, CDDP, and epinephrine or CDDP and epinephrine without the collagen matrix. Significantly higher resection bed drug levels of platinum were achieved through the use of the novel collagen matrix than through the use of CDDP and epinephrine alone (P < 0.05). The results of this study indicate that tumor bed treatment with CDDP and a unique collagen matrix drug-delivery vehicle produces prolonged high resection bed levels of platinum and prevents local tumor recurrence.

Animals↗
PubMed1995

Identification and screening of 416 patients with chronic hepatitis at high risk to develop hepatocellular cancer.

OBJECTIVE: The authors performed a prospective trial to screen patients with chronic hepatitis B or C virus (HBV, HCV) infections to (1) determine the incidence of asymptomatic hepatocellular cancer and (2) identify the subgroups at highest risk to develop hepatocellular cancer. METHODS: Four hundred sixteen patients with chronic hepatitis of more than 5 years' duration were evaluated (340 HCV, 69 HBV, 7 both). All underwent hepatic ultrasound and measurement of serum alpha-fetoprotein every 3 months. Liver biopsy was performed on entry into the study to determine the severity of hepatitis-related liver injury. RESULTS: Initial screening identified asymptomatic hepatocellular cancer in 33 patients (7.9%). Three additional liver cancers were detected during the 1st year of follow-up, bringing the overall incidence to 8.6%. Treatment with curative intent was possible in 22 of these patients (61.1%), whereas 14 (38.9%) had advanced disease. Thirty-five of these hepatocellular cancers occurred in a subset of 140 patients (25% incidence) with liver biopsies showing severe chronic active hepatitis, cirrhosis, or both, and one hepatocellular cancer occurred among the 276 patients (0.4%) with histologically less severe liver injury (p < 0.0001, chi square test). CONCLUSIONS: This screening study in patients with chronic HBV or HCV infection demonstrates (1) that the yield of asymptomatic hepatocellular cancer on initial screening is 7.9% and (2) that patients with severe chronic active hepatitis, cirrhosis, or both are at extremely high risk to develop hepatocellular cancer (25%). On the basis of these results and the finding of a significant number of small; treatable hepatocellular cancers (61.1%), the authors recommend hepatocellular cancer screening every 3 months for the subset of high-risk patients.

Adult↗
PubMed1995

[Stapling reconstruction after gastric resection. Proposed technical variation].

The authors, considering their experience in the use of stapler, suggests a technical modification of the typical gastroenteral anastomosis, to avoid some surgical complications of the mechanical anastomosis. This new technique, using two GIA 80, reproduces an handmade anastomosis. This suture is easy and fast, physiologic and safe.

Anastomosis, Surgical↗