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Biomedical subjects

S Guadagni

Publications and source records attributed to S Guadagni.

At least 19 recordsLinked to original sources
PubMed2006

Hypoxic abdominal stop-flow perfusion in the treatment of advanced pancreatic cancer: a phase II evaluation/trial.

In the past decade, some authors have reported objective responses and prolonged median survival times using hypoxic abdominal perfusion (HAP) for the treatment of advanced pancreatic cancer. However, these promising results have not been confirmed by others, making it difficult to define the effectiveness of this loco-regional chemotherapy. The aim of this study, therefore, was to evaluate the response rate, time to disease progression and overall survival following HAP treatment of 22 consecutive patients with advanced pancreatic tumors. Within the period from 1999 to 2003, 22 patients with histological diagnosis of unresectable stage III/IV pancreatic cancer, not responsive to systemic chemotherapy, were treated with mitomycin C 30mg/m(2) and cisplatin 60mg/m(2) by HAP (stop flow technique). Immediately after perfusion, hemofiltration was performed to reduce systemic side toxic effects. Responses were assessed by CT-scan 30days from the end of treatment. Minor or partial responses were confirmed by a second CT-scan 4weeks later. Following 26 treatment cycles no death or technical complications were recorded; four patients (18.2%) achieved a partial response, 2 (9.1%) a minimal response and 13 (59.1%) stable disease. The remaining 3 patients (13.6%) showed progression of the disease. The median time to disease progression was 3 months (range 1-10). The median survival time from the start of regional chemotherapy was 6 months (range 1.9-16), with a 1-year survival rate of 9%. Our data show that HAP is a relatively effective second-line treatment for advanced stage pancreatic cancer with a low complication rate. We do not concur with the opinion of others that HAP is an inactive treatment approach. However, taking into account the invasiveness of this procedure, and associated morbidity and cost, HAP would not appear to be preferable to less invasive loco-regional chemotherapeutic alternatives.

Aged↗
PubMed2004

Hemodynamic variations during thoracic and abdominal stop-flow regional chemotherapy.

AIMS: The aim of this study was to study hemodynamic modifications during thoracic and abdominal stop-flow regional chemotherapy and to evaluate the need for routine hemodynamic monitoring during such kind of procedures. METHODS: Thirty patients, aged 17-67 years, ASA physical status II-III, scheduled for thoracic (group A, n = 15), and abdominal (group B, n = 15) stop-flow regional chemotherapy were enrolled. Heart rate (HR), electrocardiogram lead I and V(5), end tidal carbon dioxide (ETCO(2)), arterial oxygen saturation (SaO(2)), systolic, diastolic and mean arterial pressure (SBP, DBP, MAP), mean pulmonary arterial pressure (MPAP), pulmonary capillary wedge pressure (PCWP), central venous pressure (CVP), cardiac output (CO), stroke volume (SV), stroke index (SI), systemic vascular resistance (SVR), pulmonary vascular resistance (PVR), left cardiac work (LCW), right cardiac work (RCW), left cardiac work index (LCWI), right cardiac work index (RCWI), cardiac index (CI), and body O(2) consumption (VO(2)) were recorded. RESULTS: After aortic and inferior vena cava endovascular occlusion (T(1)), a significant reduction of CO and SV, associated with an increase of CVP, MAP, PAPM and PCWP were observed. A concomitant reduction of CI and increase of SVR and PVR were registered. The VO(2) was significantly reduced compared to basal values in both groups. After deflating aortic and vena cava balloons (T(2)), CO, SV and CI increased with respect to basal value p < 0.05) whereas MAP, CVP, PAPM, PCWP and calculated parameters (SVR, PVR) showed a significant reduction compared to T(1). The oxygen consumption was significantly higher than that of basal values p < 0.05. After hemofiltration (T(3)), all hemodynamic variables were comparable with the basal values. Modifications of direct and calculated parameters, during the stop-flow period, showed a similar trend in both study groups, without any statistically significant difference. No ST modifications at ECG were noted during all perioperative period. CONCLUSIONS: The results of this study have confirmed in both groups, the safety of stop-flow regional chemotherapy procedure, despite endovascular occlusion of the aorta and inferior cava vein. The hemodynamic and oxygenation changes are reversible and did not produce any ST modifications at ECG during all perioperative period. Routine pulmonary artery catheterization is thus unnecessary, except in high cardiac risk patients.

Adolescent↗
PubMed2004

Thoracic stop-flow perfusion in the treatment of refractory non small cell lung cancer.

This study was undertaken to determine the survival of patients with unresectable and refractory non small cell lung cancer (NSCLC) submitted to thoracic stop-flow perfusion (TSP). Forty-five patients with NSCLC confined to thoracic region entered the study. All 45 patients had been pretreated with some form of chemotherapy and had progression of disease. The cytostatic regimen was mitomycin 10 mg/m2, navelbine 25 mg/m2 and cisplatin 60 mg/m2. In 39/45 patients, immediately after TSP, hemofiltration was performed to reduce systemic side effects There were 16/45 responses to the first TSP (CR 0; PR 16): a response rate of 35.6%. Median time to progression was 4 months. Median survival was 7.5 months.1-year survival rate was 36.4%, 2-year survival rate was 14%, and 3-year survival rate was 5.7%.

Adult↗
PubMed2004

Hepatic intra-arterial chemotherapy (HIAC) of high dose mitomycin and epirubicin combined with caval chemofiltration versus prolonged low doses in liver metastases from colorectal cancer: a prospective randomized clinical study.

A multicenter randomized study comparing high dose of mitomycin and epirubicin given as hepatic intra-arterial chemotherapy (HIAC) combined with caval chemofiltration (CF) versus low doses of the same drugs in unresectable liver metastases from colorectal cancer showed a significant improvement in the survival rate of the 20 patients treated with high dose compared to the 22 patients treated with low doses with a 1 year survival of 69% vs 39%. The median survival was 17 vs 11 months and the responses were 65% vs 33%. Toxicity was colangitis in 50% of patients considered. The extrahepatic progression was similar in the two groups (7/20 vs 8/22).

Antineoplastic Combined Chemotherapy Protocols↗
PubMed2004

Intra-arterial hepatic chemoembolization in liver metastases from neuroendocrine tumors: a phase II study.

Neuroendocrine tumors, particularly those of gastrointestinal tract origin, have a predisposition for metastasizing to the liver, causing parenchymal substitution and paraneoplastic syndrome. Lipiodol embolization combined with anticancer drugs is a recent tool in regional therapy. It has been proven that chemoembolization reduces tumor bulk and hormone levels, and that it palliates the symptoms of many patients with liver-dominant neuroendocrine metastases. Beginning in December 1988, ten patients with unresectable and chemotherapy-refractory liver metastatic neuroendocrine tumors were treated with chemoembolization based on a mixture of lipiodol, mitomycin, cisplatin, epirubicin, followed by gelfoam powder and contrast media. Toxicity encountered included: upper right quadrant pain requiring narcotics, elevation of lactate dehydrogenase, alkaline phosphatase, and transaminases. One patient had liver abscess and persistent fever for 2 weeks. We obtained two complete remissions lasting 12 and 34 months and 5 partial remissions. The median survival was 22 months. Four patients had urinary elevation of 5-hydroxyindolacetic acid (5-HIAA). They showed more than a 75% decrease in urinary secretion after treatment. In a patient with transplanted liver we noticed a partial response lasting 7 months. We conclude that chemoembolization will improve the clinical condition of a significant percentage of patients with liver metastases, that future therapy of carcinoid tumors will be based on specific tumor biology and that treatment will be customized for each individual patient combining the use of cytoreductive procedures including radiofrequency ablation, laser treatment and chemoembolization.

Adult↗
PubMed2003

Loco-regional perfusions (stop-flow techniques): state of art and future.

The treatment of primary advanced or unresectable recurrent cancers is still one of the main medical challenges. The Stop-flow perfusion has been used as loco-regional chemotherapy based on blood supply blockage of the tumour-bearing area. The aim of the present paper is to report the personal experience in the clinical use of stop-flow perfusions and discuss about future perspectives of research. Since December 1997 more than 400 Stop-flow perfusions have been performed at University of L'Aquila. The following types of indication have been selected: recurrent unresectable rectal cancer, advanced pancreatic cancer, thoracic lymphomas, recurrent non-small cell lung cancer, recurrent pelvic and limb melanoma, and recurrent limb melanoma. In this paper results are presented in terms of median survival. For recurrent rectal cancer median survival was 12.2 months, for advanced pancreatic cancer 9.6 months, for thoracic lymphomas 16 months, for recurrent non-small cell lung cancer 21 months, for recurrent pelvic and limb melanoma 34.4 months, for recurrent limb melanoma 23.8 months. Based on these encouraging results, Stop-flow perfusion should be considered an effective approach to locally advanced cancers. Future fields of research include personalized chemotherapy and perfusion under hyperthermic conditions.

Antineoplastic Agents↗
PubMed2001

Hypoxic pelvic perfusion with mitomycin C using a simplified balloon-occlusion technique in the treatment of patients with unresectable locally recurrent rectal cancer.

HYPOTHESIS: To evaluate the role of hypoxic pelvic perfusion in providing therapeutic options for palliation without relevant complications in a homogeneous group of patients with unresectable locally recurrent rectal cancer who are nonresponders or have disease progression after the standard treatments. DESIGN: Nonrandomized and noncontrolled phase II experimental study. SETTING: University hospital, L'Aquila, and the National Cancer Institute, Naples and Milan, Italy. PATIENTS: Eleven patients had symptomatic unresectable pelvic recurrent rectal cancer. The mean +/- SD product of the 2 maximum perpendicular diameters of the recurrent cancer was 24.2 +/- 11.0 cm(2) (range, 10-48 cm(2)). Tumor fixation to the pelvic side walls or proximal sacrum were the main criteria for unresectability. All patients were free from extrapelvic disease and had a life expectancy longer than 3 months. INTERVENTION: Patients were submitted to one course of pelvic perfusion with mitomycin C (MMC) (25 mg/m(2)) by means of a simplified balloon occlusion technique. A pharmacokinetic evaluation of the procedure was also performed. MAIN OUTCOME MEASURES: Response rate and time to disease progression were the primary endpoints; overall survival was the secondary endpoint. RESULTS: Mean +/- SD value of the ratios of pelvic MMC area under the plasma concentration curve (0 to 20 minutes) (AUC(0-20)) to systemic MMC AUC(0-20) was 13.30 +/- 6.52. During the procedures there were no technical, hemodynamic, or vascular complications, and no deaths occurred during surgery or in the postoperative period. The response rate was 36.3% (95% confidence interval [CI], 6.5%-66.1%). Pain response rate was 45.4% (95% CI, 16.6%-76.2%). Median survival was 12.2 months (range, 5.7-19.5 months). Median time to disease progression was 6 months (range, 3-8 months). Two-year overall survival was 9.1%. CONCLUSIONS: Hypoxic pelvic perfusion with MMC is a safe and good palliative treatment for patients with unresectable locally recurrent rectal cancer. Further studies are necessary to establish if a different sequence in the multimodular treatment of these patients could be more useful.

Antibiotics, Antineoplastic↗
PubMed2001

Regional plus systemic chemotherapy: an effective treatment in recurrent non-small cell lung cancer.

AIMS: This study was undertaken to determine the activity and toxicity of regional chemotherapy using an isolated thoracic perfusion (ITP) technique as second-line treatment for patients with advanced and recurrent non-small cell lung cancer (NSCLC). METHODS: Eighteen patients with relapsed NSCLC confined to the thoracic region entered the study and received regional chemotherapy using ITP plus low-dose systemic chemotherapy. All 18 patients had been pre-treated with some form of chemotherapy, surgery and/or radiotherapy. The cytostatic regimen had two components: (1) ITP using mitomycin 10 mg/m(2), navelbine 25 mg/m(2)and cisplatin 30 mg/m(2)on day 1; (2) systemic chemotherapy with 5-fluorouracil 250 mg/m(2)and cisplatin 20 mg/m(2)given as a continuous infusion over 24 h on days 1-4. RESULTS: All 18 patients were assessable for toxicity, tumour response and survival. There were 10/18 responses (CR 0; PR 10): a response rate of 56%. Side-effects were transient and acceptable. No treatment-related death occurred. Median survival was 21 months and the 1-year survival rate was 75%. CONCLUSIONS: Regional chemotherapy using ITP plus low-dose systemic chemotherapy is effective in recurrent advanced NSCLC, with an encouraging survival outcome.

Adult↗
PubMed2000

Evaluation of the Maruyama computer program accuracy for preoperative estimation of lymph node metastases from gastric cancer.

Controversy still exists about the optimal lymph node (LN) dissection for potentially curable gastric cancer. For rational LN dissection it is important to know the incidence of metastasis at each LN station. For this purpose a computer program was developed using data from 4302 primary gastric cancers treated at the National Cancer Center Hospital in Tokyo between 1969 and 1989. To evaluate the accuracy of the computer program, the differences between the individual reports generated by the computer and the stored data were investigated in 282 Italian patients submitted to curative gastrectomy and D2 or more extended LN dissections for gastric cancer. Receiver operating characteristic (ROC) analysis was used to assess the sensitivity and specificity of the program for predicting LN metastases in each of the 16 regional LN stations. The computer program showed good predictive ability for LN metastases in most of the 16 LN stations, as the areas under the curve ranged from 0.741 (station 15) to 0.944 (station 8), with a mean of 0.856. A critical cutoff point of 18% of the program's expected percentage was the value maximizing the validity of the prediction. Using an "absolute" cutoff point of 0%, the overall rate of false-negative (FN) predictions in 176 N+ patients was 11.9%; of these, 11 (6.2%) were absolute FNs, in which the program totally failed to estimate LN metastases; the remaining 10 cases (5.7%) were relative FNs because the specific prediction was positive for a different depth of stomach invasion. The low number of D3/D4 lymph-adenectomies in the historical database may affect the low estimate of metastases to N3/N4 nodes generated by the program. Based on these data, the program predicts with good accuracy the extent of LN metastases from gastric cancer, but it is not recommended for directing the surgeon to perform more extensive lymphadenectomy.

Chi-Square Distribution↗
PubMed2000

Intra-arterial chemotherapy for unresectable pancreatic cancer.

BACKGROUND: A phase II trial of a new intra-arterial chemotherapy regimen for unresectable pancreatic cancer (UPC). PATIENTS AND METHODS: Ninety-six patients with UPC were treated with intra-arterial chemotherapy at three-weekly intervals. The schedule used was FLEC: 5-fluorouracil 1000 mg/m2, folinic acid 100 mg/m2, carboplatin 300 mg/m2; epirubicin 60 mg/m2. RESULTS: The overall response rates by CT-scan evaluation were: 15% partial response (PR), 44% stable disease (SD), 17% progressive disease (PD). The overall median survival was 9.9 months, and 10.6 and 6.8 for UICC stage III and IV, respectively. Pain reduction occurred in 42% of patients. A weight gain > 7% from baseline occurred in 8% of patients. A total of 341 courses of FLEC were administered. Grade 3-4 hematological toxicity was seen in 25% of patients; ematemesis in 4%; grade 3 gastrointestinal toxicity in 3%; and grade 3 alopecia in 16%. One sudden death, a pre-infarction angina, and a transitory ischemic attack were observed. The only complication related to the angiographic procedure was an intimal dissection of the iliac artery. CONCLUSIONS: The intra-arterial FLEC regimen was well tolerated and active. It requires only one day of hospitalization. Efficacy could only be assessed in a randomized study against a gemcitabine containing regimen.

Adenocarcinoma↗
PubMed2000

Significance of duplex/colour Doppler sonography in hepatic arterial chemotherapy for patients with liver metastases from colorectal carcinoma.

AIMS: The aim of the study was to evaluate the importance of duplex/colour Doppler ultrasound in a protocol of hepatic regional chemotherapy, by measuring the blood flow in the hepatic artery, portal vein, hepatic veins, and inferior caval vein of patients with unresectable liver metastases from colorectal carcinoma. METHODS: Thirty-nine consecutive subjects were selected for this study, including 21 patients who had unresectable histologically confirmed liver metastases from colorectal carcinoma (Group A), and 18 asymptomatic volunteers as normal controls (Group B). All subjects of Groups A and B were examined using duplex/colour Doppler sonography. After the ultrasound study, all patients of Group A were submitted to the administration of high dose mitomycin C into the hepatic artery, with concomitant detoxication of post-hepatic venous blood. RESULTS: The mean value of the hepatic artery blood flow was significantly higher (P=0.0009) in liver metastases patients (361 ml/min, SEM=24 ml/min) than in normal controls (245 ml/min, SEM=20 ml/min). Also, the mean Doppler perfusion index was higher in liver metastases patients than in normal controls. For each patient of Group A, the total dose of mitomycin C to be infused was calculated based on the blood flow in the hepatic artery. In this way the concentration of mitomycin C in the hepatic artery was always greater than 3 microg/ml. The duration of detoxication was calculated based on the blood flow in the inferior caval vein. For two patients only, the blood flow was lower than 1000 ml/min, with the necessity to protract the duration of detoxication over 2 hours. CONCLUSIONS: The measurement of the blood flow in hepatic vessels of patients with liver metastases seems to be very important in establishing the total dose of drug which has to be infused in hepatic arterial chemotherapy, and to determine the duration of concomitant detoxication of post-hepatic venous blood.

Adult↗
PubMed1999

Chronic lymphocytic leukaemia and neuroendocrine cancer.

We report a unique association between neuroendocrine cancer and chronic lymphocytic leukaemia (CLL) in a 63-year-old man. Neuroendocrine cancer was resistant to various conventional treatments and following locoregional progression we treated the patient with hypoxic pelvic perfusion of cisplatin 100 mg/m2 plus mitomycin 40 mg/m2, using the stopflow method, for three cycles: a dramatic and surprising reduction of > 75% in the evaluable lesions was observed. The cumulative effect of treatment produced a complete response from CLL. At cytogenetic examination the neuroendocrine cells were diploid, whereas CLL cells showed trisomy 12. Moreover, deletion of the short arm of chromosome 3 was found in both neoplastic populations. Whether the abnormality seen on chromosome 3 in the two diseases represents a critical event is not known.

Chromosome Deletion↗
PubMed1999

Combination of granulocyte-macrophage colony-stimulating factor (GM-CSF) anf erythropoietin (EPO) for the treatment of advanced non-responsive chronic lymphocytic leukemia.

We report the use of a colony-stimulating granulocyte-macrophage factor (GM/CSF) and erythropoietin (EPO) combination as salvage treatment in four heavily-pretreated patients with refractory/ recurrent B-CLL. Induction therapy was subcutaneous GM-CSF 2.5 microg/ kg, and EPO, 150 units/kg both daily for the first 14 d. Maintenance therapy was GM-CSF on days 1, 3 and 5 and Epo on days 2, 4 and 6 at the same doses with weekly recycling. All the patients responded favourably. A significant reduction of lymphocytosis, lymphoadenomegaly, and organomegaly was obtained within one month of therapy. The number of infections and transfusional requirement decreased dramatically. The hemoglobin increased to over 11 g/dl in 3 out of 4 patients. With a median follow-up of 11 months (range 5-13) we observed 4 partial responses (NCI/IWCLL) and only one progression after a 10-month partial response. This combination regimen seems very active, safe and easy to administer. It may represent a promising therapeutical option in heavily pretreated patients. Further clinical and biological studies on a larger cohort of patients are needed to confirm these preliminary data, to clarify the hypothetical interactions between these cytokines and B-CLL cell proliferation pathways, and to establish if this therapy may have an impact on survival.

Administration, Cutaneous↗
PubMed1998

Pharmacokinetics of mitomycin C in pelvic stopflow infusion and hypoxic pelvic perfusion with and without hemofiltration: a pilot study of patients with recurrent unresectable rectal cancer.

This pilot study was conducted to evaluate the advantage in drug delivery for regional chemotherapy in patients with unresectable recurrent rectal carcinoma by different methods. For this research, the pharmacokinetic advantages of mitomycin C delivery by four different methods were compared: intraaortic infusion with aortic stopflow; intraaortic infusion with inferior vena cava stopflow; intraaortic infusion with aortic and inferior caval vein stopflow (hypoxic pelvic perfusion); and hypoxic pelvic perfusion with hemofiltration. The results of this study indicate that pelvic stopflow infusion followed by hypoxic pelvic perfusion significantly increases mitomycin C concentrations in the blood coming from the tumor site. Also, use of hemofiltration reduces mitomycin C levels in peripheral blood after high-dose regional chemotherapy. Further investigations involving more patients should be carried out in the future to validate these results.

Algorithms↗