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Biomedical subjects

B Daniele

Publications and source records attributed to B Daniele.

At least 19 recordsLinked to original sources
PubMed2002

Tamoxifen in the treatment of hepatocellular carcinoma: 5-year results of the CLIP-1 multicentre randomised controlled trial.

BACKGROUND: In 1998, when data of a meta-analysis on tamoxifen in the treatment of hepatocellular carcinoma (HCC) had suggested a little advantage for this treatment, we published the results of a multicenter randomised controlled trial, that showed no survival benefit for tamoxifen vs. control. Here we report an updated analysis of the study results 4.5 years after the closure of enrollment. METHODS: The study had a planned sample size of 480 patients. Patients with any stage HCC were eligible, irrespective of locoregional treatment. Tamoxifen was given orally, 40 mg/die, from randomisation until death. RESULTS: 496 patients were randomised by 30 Institutions from January 1995 to January 1997. Information was available for 477 patients. As of July 2001, 374 deaths (78%) were recorded, and median survival times were 16 and 15 months (p=0.54), in the control and tamoxifen arm. Data were further analysed separately for advanced patients and for those eligible to potentially curative locoregional treatments: relative hazard of death for patients receiving tamoxifen was equal to 0.98 (95% CI 0.76-1.25) for the former group and 1.38 (95% CI 0.95-2.01) for the latter. The prognostic score recently devised by our group (CLIP score) was, as expected, strictly correlated (p<0.0001) to the locoregional treatment received and strongly correlated with prognosis. CONCLUSIONS: the update of the present study confirms that tamoxifen is not effective in prolonging survivals, both in advanced patients and in those potentially curable and that the CLIP score is able to predict prognosis.

Carcinoma, Hepatocellular↗
PubMed2001

Survival and quality of life in gastrointestinal tumors: two different end points?

BACKGROUND: In gastrointestinal tumors, the traditional end point of medical treatment was represented mainly by survival. In the last few years, however, there has been an increasing awareness about the role of quality of life. DESIGN: This paper seeks to discuss these two important end points and their relationship in colorectal, gastric, pancreatic and liver cancers. RESULTS: Chemotherapy has doubled survival in comparison with best supportive care in gastrointestinal tumors. A subjective response, represented by a decrease in cancer-related symptoms is expected in about half of the symptomatic patients in colorectal and gastric cancer. In pancreatic cancer, the positive results in terms of clinical benefit helped define the role of chemotherapy. Although clinical benefit does not represent a validated tool to measure quality of life, it can be a first step in the definition of new, simpler tools to assess this end point. The frequent presence of a serious concomitant disease, liver cirrhosis, in patients with hepatocellular carcinoma (HCC) usually prevents the use of chemotherapy in these tumors, which are often treated with locoregional treatments. Unfortunately, their impact on the survival and quality of life of these patients has never been adequately assessed. CONCLUSIONS: In many gastrointestinal cancers, chemotherapy can produce a survival gain and an improvement in the quality of life. Further studies assessing new drugs and/or combinations should focus on these aspects and their relationships. In particular, the impact of treatments of HCC on both survival and quality of life must be investigated by well-designed prospective trials. When assessing the value of a particular anticancer treatment, it is important to consider the impact it may have not only on survival but also on quality of life. This is particularly so for cancer patients, whose life expectancy may be short.

Carcinoma, Hepatocellular↗
PubMed2001

Effect of chemotherapy with 5-fluorouracil on intestinal permeability and absorption in patients with advanced colorectal cancer.

5-Fluorouracil (5-FU), in association with leucovorin (LV), is the most used chemotherapy agent in the treatment of colorectal cancer. Response rate, as well as side-effect incidence, increases with the dose intensity of regimens that are used. The most common dose-limiting toxicity for 5-FU/LV modulation is diarrhea. To assess the modification of small intestinal function, we investigated the changes in intestinal permeability (IP) and intestinal absorption (IA) in 41 chemo-naive patients (21 men and 22 women; mean age, 61 +/- 9 years) with advanced colorectal cancer after treatment with the association of folinic acid and 5-FU. After chemotherapy administration, we found a marked increase in IP and a reduction in IA, measured as cellobiose-mannitol (CE-MA) ratio (p < 0.0001) and D-xylose absorption (p = 0.0001), respectively. Patients who experienced diarrhea have an increase in CE-MA ratio and a reduction in D-xylose absorption values, both statistically significant. Cellobiose-mannitol ratio and D-xylose absorption tests can be used for the assessment of toxic effect of 5-FU on mature intestinal epithelium and also for evaluating the role of cytoprotective agents.

Antimetabolites, Antineoplastic↗
PubMed2001

Ischemic colitis associated with paclitaxel.

Systemic chemotherapy can be complicated by colonic toxicity, which usually determines the onset of pseudomembranous colitis and, rarely, of ischemic colitis in patients with cancer. This report describes the case of a 49-year-old woman with liver metastases from a neuroendocrine tumor of unknown origin who developed mild ischemic colitis after chemotherapy with carboplatin and paclitaxel. The patient developed symptoms of gastrointestinal toxicity with abdominal pain and bloody diarrhea, which resolved in about 10 days. She had a normal white blood cell count throughout her illness; the assay of stool specimens for Clostridium difficile toxins and the stool cultures were both negative. A sigmoidoscopy showed a mild, transient ischemic colitis, which was confirmed by pathologic examination of the biopsy specimens. Although carboplatin is not related to severe colonic cytotoxicity, it has been previously reported that paclitaxel induces necrosis of the gastrointestinal mucosa and inhibits angiogenesis. Pseudomembranous colitis is the most frequent complication in patients with cancer who undergo paclitaxel-based chemotherapy and develop gastrointestinal toxicity. Once C. difficile infection has been excluded, a diagnosis of ischemic colitis should be considered, especially in patients with cancer who have normal white blood cell counts.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed2001

Oral glutamine in the prevention of fluorouracil induced intestinal toxicity: a double blind, placebo controlled, randomised trial.

BACKGROUND: 5-Fluorouracil (FU) in association with folinic acid (FA) is the most frequently used chemotherapeutic agent in colorectal cancer but it often causes diarrhoea. Animal and human studies suggest that glutamine stimulates intestinal mucosal growth. AIM: To determine if oral glutamine prevents changes in intestinal absorption (IA) and permeability (IP) induced by FU/FA. METHODS: Seventy chemotherapy naive patients with colorectal cancer were randomly assigned to oral glutamine (18 g/day) or placebo before the first cycle of FU (450 mg/m(2)) and FA (100 mg/m(2)) administered intravenously for five days. Treatment was continued for 15 days, starting five days before the beginning of chemotherapy. IA (D-xylose urinary excretion) and IP (cellobiose-mannitol test) were assessed at baseline and four and five days after the end of the first cycle of chemotherapy, respectively. Patients kept a daily record of diarrhoea, scored using the classification system of the National Cancer Institute (Bethesda, Maryland, USA). Duration of diarrhoea was recorded and the area under the curve (AUC) was calculated for each patient. RESULTS: Baseline patient characteristics and basal values of IP and IA tests were similar in the two arms. After one cycle of chemotherapy, the reduction in IA (D-xylose absorption) was more marked in the placebo arm (7.1% v 3. 8%; p=0.02); reduction of IP to mannitol was higher in the placebo arm (9.2% v 4.5%; p=0.02); and urinary recovery of cellobiose was not different between the study arms (p=0.60). Accordingly, the cellobiose-mannitol ratio increased more in the placebo arm (0.037 v 0.012; p=0.04). Average AUC of diarrhoea (1.9 v 4.5; p=0.09) and average number of loperamide tablets taken (0.4 v 2.6; p=0.002) were reduced in the glutamine arm. CONCLUSIONS: Glutamine reduces changes in IA and IP induced by FU and may have a protective effect on FU induced diarrhoea.

Administration, Oral↗
PubMed2001

Prognostic value of serum biological markers in patients with hepatocellular carcinoma.

PURPOSE: Prognosis of patients with hepatocellular carcinoma (HCC) is assessed by using indexes based on clinical and instrumental parameters. The Cancer of the Liver Italian Program (CLIP) staging system combines the Child-Pugh classification with tumor size, portal invasion, and alpha-fetoprotein and predicts the outcome of HCC patients more precisely than the Okuda staging system. Serum levels of a number of biological variables have been found to be increased in patients with HCC and are associated with different outcomes. Our aims in this study were to test the prognostic role of the serum levels of soluble intercellular adhesion molecule-1 (sICAM-1), soluble interleukin-2 receptor (sIL-2R), interleukin 6 (IL-6), and anti-p53 and to assess whether the addition of any of the above serum markers could further improve the predictive ability of the CLIP score. EXPERIMENTAL DESIGN: Serum levels of sICAM-1, sIL-2R, IL-6, and anti-p53 were assayed in 80 patients with HCC and correlated with their outcomes. Nonparametric procedures were applied to test correlations between serum sICAM-1, sIL-2R, IL-6, anti-p53, and other prognostic factors. For survival analyses, the product-limit method, log-rank test, and Cox proportional hazards model were applied. RESULTS: Only serum levels of sIL-2R correlated with survival, which was longer for patients with lower values (< or =950 units/ml). However, with multivariate analysis sIL-2R did not confirm its predictive role when tested with the CLIP score as a covariate, with a hazard of death of 1.51 (95% confidence interval, 0.76-3.01). CONCLUSIONS: Serum levels of sICAM-1, sIL-2R, IL-6, and anti-p53 are not useful as prognostic factors for HCC in clinical practice. They do not improve the predictive ability of the CLIP score.

Aged↗
PubMed2001

Carotid endarterectomy: a retrospective analysis. Microendarterectomy and transcranial Doppler ultrasound monitoring.

BACKGROUND: Analyses of the results obtained following our protocol for the surgical therapy of carotid artery stenosis is the aim of this study. METHODS: Ninety-one procedures were performed on 84 patients by the same surgical team. Indications for carotid endarterectomy (CEA) were 50-70% internal carotid artery (ICA) stenosis in 8% of the patients (100% symptomatic), 70-90% stenosis in 67% (64% symptomatic) and 90-99% ICA stenosis in 25% of our patients (33% symptomatic). Carotid shunt during arterial cross-clamp was only used in 4 cases (4.4%) following trans-cranial Doppler ultrasound (TCD) intraoperative monitoring findings. Operative microscope or surgical loupes were used for the complete removal of atheroma and the direct suture of the arteriotomy. Heparin was only antagonised in selected cases. RESULTS: No mortality and no permanent deficit related to ischemic events were present in our patients; a transient neurological deficit occurred in 1 case (1.1%). Two patients died (2.2%): 1 due to myocardial infarction and the second one to bronchopneumonia. Transient peripheral nerve deficits were noted in 2 cases. CONCLUSIONS: In order to reduce to a minimum ischemic risks during CEA, our preliminary experience advises microsurgical technique for the complete removal of the atheroma and suture, TCD evaluation of collateral reserve during cross-clamping, and the use of randomised multicenter studies guidelines for the selection of patients. More attention must also be given to postoperative care, since hemodynamic instability represents the main risk for our patients. Overnight intensive care unit (ICU) surveillance in all patients may help to avoid fatal complications.

Aged↗
PubMed2000

Originality, benefits and difficulties of clinical research performed by cooperative groups: the experience of an Italian Lung Cancer Study Group.

In the past years, clinical research performed by cooperative groups achieved important results. The trials of adjuvant chemotherapy in breast and colorectal cancer or neoadjuvant treatment in osteosarcoma are cornerstones in the history of medical oncology and highlight the importance of research performed by cooperative groups. However, there are many difficulties for the functioning of cooperative groups: financial support, slow enrollment of patients in clinical trials, insurance related problems and quality control of clinical research. In the last few years, our group focused its interest on lung cancer, both small cell and non-small cell. The group is composed of experts from various disciplines in oncology. The clinical interest of the group has focused on two aspects of lung cancer: quality of life and treatment of elderly patients. Our group is giving significant contributions to the field of lung cancer. Today, large controlled clinical trials are ongoing.

Aged↗
PubMed2000

The role of chemotherapy in the management of gastric cancer.

Despite a marked decline in the incidence of gastric carcinoma in Western countries, the majority of patients presents with advanced inoperable tumors. In this setting, usually the aim of therapy is palliation, with the exception of chemotherapy administered in the attempt to downstage the tumor and to facilitate potentially curative surgery in patients with locally advanced nonmetastatic disease. This review will focus on the use of chemotherapy for advanced gastric cancer and after curative surgery, providing an overview of future directions for clinical research: preoperative (neoadjuvant) systemic chemotherapy, intraperitoneal treatment, and newer drugs.

Antimetabolites, Antineoplastic↗
PubMed2000

Levovist-enhanced Doppler sonography versus spiral computed tomography to evaluate response to percutaneous ethanol injection in hepatocellular carcinoma.

The aim of the current study was to compare Levovist-enhanced power Doppler (PD) imaging with contrast-enhanced spiral computed tomography (CT) in the evaluation of intratumoral vascularity of hepatocellular carcinomas at diagnosis and after percutaneous ethanol injection (PEI). Nineteen patients with hepatocellular carcinoma (HCC) underwent PD with and without Levovist and spiral CT at diagnosis and 1 month after PEI treatment. Compared to spiral CT at baseline evaluation, the PD showed intratumoral vascularity in 36.8% of the cases; this percentage reached 78.9% after Levovist enhancement. One month after PEI, only 5 out of 19 treated HCCs appeared as hypodense areas at CT and showed no contrast enhancement. Only 3 of the 14 patients with a positive spiral CT scan were positive at the PD performed without the Levovist administration (sensitivity, 21.4%). The use of contrast-enhanced ultrasonography led to detection of residual signal in six other HCCs treated by ethanol injection (sensitivity, 64.2%). We confirm that spiral CT is the most sensitive and accurate technique in evaluating the effect of ethanol injection in HCC. It correctly identifies most cases of treatment failure as enhanced areas within the lesion. The lower rate of detection of tumoral vascularity by Doppler sonography was significantly increased by Levovist. The evidence of residual vascularity within HCC at Levovist Doppler sonography allows the targeting of additional ethanol injections.

Aged↗
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

Mucosal expression of carcinoembryonic antigen and carbohydrate antigen 19-9 in patients with gastritis and gastric cancer.

Sixty-eight patients (45 males, 23 females) were studied in order to assess the usefulness of mucosal tissue concentrations of both carcinoembryonic antigen (CEA) and carbohydrate antigen 19-9 (CA19-9) in detecting patients at high risk for gastric cancer. CEA and CA19-9 were assayed on cytosol obtained from multiple endoscopic biopsies of 41 patients with chronic superficial gastritis, 18 with chronic atrophic gastritis, and 9 with gastric cancer. Mucosal tissue concentrations of both CEA and CA19-9 increased from chronic superficial gastritis to chronic atrophic gastritis and to gastric cancer (p = 0.005 and p = 0.002, respectively). Mucosal CEA levels in patients with intestinal metaplasia (IM) were significantly higher than in nonmetaplastic mucosa (p = 0.04). Epithelial dysplasia was associated with higher, though not significant, tissue concentrations of both CEA and CA19-9 when compared with IM. Finally, a correlation between serum levels and tissue concentrations was observed only for CA19-9 (Pearson's correlation coefficient = 0.7). In conclusion, these data indicate that gastric mucosa of patients with chronic atrophic gastritis and intestinal metaplasia express high levels of both CA19-9 and CEA.

Adult↗
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

Endocrine treatment of hepatocellular carcinoma. Any evidence of benefit?

In the past 20 years, a number of studies have investigated the relationship between sex hormones and liver cancer. Experimental studies indicate that a dynamic process, with sequential modifications in the pattern of sex hormones in the serum and of sex hormone receptors in the liver, occurs progressively during hepatocarcinogenesis. Overall, it seems that both androgens and oestrogens may enhance liver carcinogenesis, while androgens may also support the growth of established liver tumours. Unfortunately, clinical studies of endocrine treatment of hepatocellular carcinoma (HCC) have not adequately tested the suggestions from biological studies. So far, no clinical trial has been performed to test the efficacy of endocrine manipulation for the chemoprevention of HCC in cirrhotic patients nor in preventing relapse after radical resection of primary HCC. Anti-oestrogens have been the most studied agents for the endocrine treatment of established HCC, although the rationale that supports their use is weaker than for anti-androgens. Studies with anti-androgens have produced prevalently negative results, due to either a lack of activity or excessive toxicity. The use of chemical castration, which theoretically could enhance the activity of antihormonal compounds, yielded no benefit at all. In summary, there is, as yet, no definitive evidence that endocrine treatment favourably affects the outcome of patients with HCC.

Animals↗