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Biomedical subjects

D Civalleri

Publications and source records attributed to D Civalleri.

At least 91 records · Page 5Linked to original sources
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Intrahepatic epidoxorubicin in metastatic and primary liver tumours: a phase II study.

Primary and metastatic gastrointestinal tumours in the liver have been treated by intrahepatic artery infusion of chemotherapeutic drugs in an attempt to increase the efficacy of the administered agents. Among the several active agents, 4' epidoxorubicin, an anthracycline analogue, was selected for this study because of the therapeutic level reached in the liver by this drug. Seven patients with primary hepatic carcinoma and twenty with metastatic adenocarcinoma of the colon to the liver received intraarterial hepatic infusion of epidoxorubicin at the dosage of 30 mg weekly. No haematological or gastrointestinal grade 3-4 toxicity was recorded, only one patient experienced transient cardiac toxicity. No objective response was observed in primary hepatic carcinoma and six objective responses, 1 complete and 5 partial (30%), were achieved in metastatic colorectal cancer patients. This results is not far from those reported with FUDR, but does not justify epidoxorubicin in colorectal cancer patients as first line intraarterial treatment.

Blood Cell Count↗
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Effect of normal saline on cisplatin pharmacokinetics and antitumor activity in mice bearing P388 leukemia.

The effect of normal saline (NS) on the antitumor activity, toxicity and pharmacokinetic of cisplatin (DDP) was investigated in BDF1 mice bearing P388 leukemia. Tumor-bearing mice received 8 or 16 mg/Kg of DDP dissolved in NS or distilled water (DW) intraperitoneally. Control animals were treated with DW or NS alone. The administration of 8 mg/Kg of DDP+NS produced a significantly better survival (P less than 0.05) compared to that observed in mice receiving DDP+DW. The proportion of long-term survivors was 3.5 times higher in the DDP+NS group (39%) compared to the DDP+DW group (11%). The administration of 16 mg/kg DDP+DW was highly toxic, resulting in early deaths (MST = 5 days) and no long-term survivors. NS protected from DDP toxicity without further improving the survival achieved following the injection of 8 mg/kg DDP+NS. Investigation of platinum pharmacokinetics showed that NS significantly decreases both plasma and tissue concentrations of total platinum, mainly through a decrease in the amount of platinum bound to high molecular weight plasma proteins. HPLC studies indicated that mice receiving 8 mg/kg DDP+NS or DDP+DW fail to show clear differences both in the total ultrafilterable platinum and unchanged DDP in plasma ultrafiltrate. Conversely, mice treated with DDP+NS had higher concentrations of platinum-species in plasma ultrafiltrate than mice receiving DDP+DW. These latter results, together with the observation that NS decreases the amount of platinum bound to plasma proteins, suggest that the effect of NS does not solely depend in vivo on the ability of the chloride ion concentration to stabilize the DDP molecule and suppress the formation of DDP metabolites, but also on its ability to prevent DDP toxicity by reducing the protein binding of DDP aquated products.

Animals↗
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[Behavior of serum proteins and lipids after jejuno-ileal bypass for obesity].

Variations in body weight, behaviour of lipidaemic fractions proteinaemia, uricaemia and uricuria, and lipid and protein absorption were studied preoperatively and at varying times following operation in five subjects who had undergone jejuno-ileal bypass for obesity. The results showed high serous NEFA and a definite, early and persistent reduction in all lipidaemic fractions after operation. The post-operative levels of serous proteins, particularly albumin, which were reduced in all subjects, reached pathological levels in two patients where proteic malnutrition following on the operation was associated with serious liver disease. The results agree with reported data. The variations in lipidic and proteic malabsorption proved to be in agreement with weight drop and the serous parameters considered. The reduction in uricaemia encountered in the five patients studied failed to agree with data reported in the Anglo-Saxon literature. This may be explained by alimentary and racial differences between the two populations of patients.

Adult↗
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Serum, urine and peritoneal fluid levels of 5-FU following intraperitoneal administration.

Seven patients with advanced colon cancer, refractory to conventional chemotherapy, and malignant disease confined to the intra-abdominal space received a total of 24 consecutive courses of ip 5-Fluorouracil (5-FU). 5-FU 1000 mg was administered in 2 L of warm (37 degrees C) dialysate daily for five consecutive days every 28 days. 5-FU concentrations in serum, peritoneal fluid and urine were measured by high pressure liquid chromatography (HPLC). The mean disappearance half-life of 5-FU from the peritoneal fluid was 1.6 hours with a mean permeability area product (PA) of 22.4 ml/min. The mean peritoneal AUC was 450 +/- 165 times greater than the mean serum AUC. Ip 5-FU treatment is well tolerated, can be safely administered on an outpatient basis and produces a significant pharmacological advantage over conventional routes of administration.

Adult↗
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[2 cases of death caused by hepatic insufficiency after jejuno-ileal bypass for obesity].

Reference is made to 2 cases of fatal liver failure following jejuno-ileal by-pass for obesity, in which necropsy shown micronodular and the rarer fragmentary necrosis, in addition to serious steatosis. Liver alterations following by-pass are usually reversible and respond to the infusion of medicaments. The indication for surgical re-establishment of continuity, in which, if timely, leads to normalisation of liver shape and function, must be chosen without hesitation when changes, albeit reversible, appear to threaten life and resist treatment, and in all cases where biopsy points to progression towards irreversible sclerosis.

Adult↗
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[Intestinal transit time in bilio-pancreatic bypass].

Transit times were evaluated in 23 obese subjects before and 1,4 and 12 months after biliopancreatic by-pass. A modified version of the method of Hinton et al. was used to determine emptying of the stomach and partial and total transit times. Emptying of the stomach was normal preoperatively. After surgery, it was almost immediate, except in two subjects with stomitis. Both transit times were virtually unchanged. Since the segment between the stomach and the ileocaecal valve is only half as long as in the normal subject, the results show that the by-pass leads to a slowing of transit that concerns the small intestine only, is quickly established, and does not change in the course of time. Evaluation of the altered anatomical and functional situation, and the absence of a correlation between the long-term behaviour of transit times on one hand and of lipid malabsorption and weight loss on the other-hand, suggest that a slower transit time must not be regarded as a compensation mechanism, except insofar as it restricts the degree of malabsorption set up immediately after surgery. Preliminary studies of enterohormonal changes following the by-pass indicate that increased glucagon and decreased motiline values are mainly responsible for slower transit times.

Adult↗
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[Isolated hyperthermic antiblastic perfusion in recurrent melanoma of the extremities].

Twenty-two patients with recurrent melanoma of the limbs, underwent Hyperthermic Antiblastic Perfusion (HAP). HAP lasted 60 min, with maximal local temperature of 40.5-42 degrees C and melphalan 10 mg/L limb volume as antiblastic agent. Fourteen patients had in-transit metastases and 8 local recurrences. Regional nodes were involved in 6 patients. Systemic leakage monitored with 125I or 99Tc ranged between 5 and 30% (mean 19%). No operative mortality nor major complications occurred. Local toxicity scored Wieberdink grade I in 6 patients, grade II in 11 and III in 5. Response rate (UICC) in the 9 patients treated with unexcised lesions was 88% (55% complete responses). After a median follow-up of 27 months (1-92) 9 patients relapsed after a median time of 17 months, and 15 patients are currently disease free, 4 of them being re-excised and one reperfused. Actuarial 5 year survival is 67%, with 45% disease free to the first relapse. Our results are consistent with the literature indicating HAP as a safe procedure with a high evidence of clinical responses.

Adult↗
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Malignant tumors in the head of the pancreas and the periampullary region. Diagnostic and prognostic aspects.

This paper analyzes the value of ultrasonography (US), computerized tomography (CT) and endoscopic retrograde cholangiopancreatography (ERCP) to establish the location, nature and resectability of carcinomas of the pancreatic head and of the periampullary region. The prognostic importance of certain pathological factors in relation to survival was also evaluated. As regards the site of origin, 112 cases with carcinoma were classified as follows: 56 pancreatic, 32 ampullary, 10 common bile duct, and 14 undefined. Papillary tumors were more accurately defined by ERCP compared to CT+US (p = 0.033), whereas CT was less accurate than US+ERCP (p = 0.05). No significant differences were found in pancreatic and common bile duct tumors. Pathological confirmation was obtained with ERCP in 54 cases (46% pancreatic, 69% papillary and 50% common bile duct). In the remaining 58 patients (including 1 chronic pancreatitis) the diagnosis was confirmed with percutaneous or intraoperative biopsy. Tumor extent was better defined by US+CT. In 42 resected patients the final pathological examination revealed an error of preoperative staging in 79% pancreatic, 59% papillary, and 83% common bile duct tumors. Tumor size, nodal status, perivascular, capsular and portal vein infiltration proved to be significant prognostic factors for pancreatic tumors. Stepwise regression identified tumor size, capsular infiltration and perivascular invasion as the most important covariates for survival. Ulceration, papillary histotype, pancreas and Oddi muscle infiltration, grading, perineural, lymphatic and vascular involvement were found to be significant in papillary tumors. The Cox proportional hazard model showed that pancreatic, Oddi muscle, perineural infiltration, and histologic type respectively represent a relative risk of 5.93, 107.36, 21.31, 20.61. The limited number of cases of common bile duct primary did not allow us to carry out statistical analysis on these tumors.

Algorithms↗
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Carcinoembryonic antigen (CEA) in serum and bile of colorectal cancer patients with or without detectable liver metastases.

It has been suggested that bile CEA levels could represent a sensitive index for the detection of occult liver metastases in colorectal cancer (CRC) patients. We measured serum and gallbladder bile CEA concentrations in a control group, in a group of patients with benign disease of the biliary tree, and in patients with CRC at different stages. Neoplastic patients without evidence of liver metastases at the time of laparotomy, but with elevated biliary CEA levels, were selected for a follow-up study. Our results indicate that (a) bile CEA levels are falsely increased in several benign biliary diseases; (b) CRC patients with detectable liver metastases have elevated biliary CEA levels; (c) high biliary CEA levels do not represent a predictive parameter for the presence of occult liver metastases in CRC patients.

Bile↗
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Effect of para-aminobenzoic acid on the pharmacokinetics and urinary excretion of cis-diamminedichloroplatinum(II) in rats.

Para-aminobenzoic acid (PABA) has been previously reported as being an inhibitor of DDP toxicity, and its use did not result in any observable loss in antitumor activity of DDP. The following studies investigated the effect of PABA on the pharmacokinetics and urinary excretion of cis-diamminedichloroplatinum(II) (DDP) in male Sprague-Dawley rats. DDP was injected i.p. at the dose of 7.5 mg/kg in normal saline alone and with a concurrent i.p. injection of PABA (100 mg/kg). The combined treatment with PABA produced a significant increase in the plasma concentrations of total platinum, without affecting the levels of platinum species in the plasma ultrafiltrate. Similar results were also obtained in additional studies in rats receiving the same dose of DDP plus PABA through different routes of administration (i.e. DDP i.v. and PABA i.p.). Both the area under the total platinum plasma concentration-time curve (AUC) up to 60 min and AUC0-120 min were increased by PABA by an average of 113% and 66% respectively. The administration of PABA in rats was followed by a substantial reduction in total urinary excretion of platinum (P < 0.05) and by a significant (P < 0.01) lower concentration of DDP derived platinum in the urine collected during the first 4 h after treatment. The renal clearance of filterable platinum was reduced by PABA by an average of 67.5% from 1.11 to 0.36 ml/min/100 g body wt. Total 24-h urinary excretion of platinum was also decreased, although not significantly, by PABA. Urine volumes from rats treated with DDP+PABA were similar to those from animals receiving DDP alone. HPLC studies indicate that PABA reacts readily with the species generated from DDP in vitro, while the agent is essentially unreactive toward the parent DDP and does not influence its decomposition rate. The overall data of this study suggest that the protective effect exerted by PABA on DDP toxicity may be at least partially due to its ability to interact with aquated DDP as well as to alter the renal excretion of platinum.

4-Aminobenzoic Acid↗
PubMedDate not supplied

Palliative chemoembolization of hepatocellular carcinoma with mitoxantrone, Lipiodol, and Gelfoam. A phase II study.

Transcatheter chemoembolization, in conjunction with various drugs, has been widely used for palliative treatment of hepatocellular carcinoma. A phase II study was carried out on mitoxantrone chemoembolization. High risk cirrhotic patients were excluded from this study. Fourteen mg/m2 mitoxantrone and up to 20 ml Lipiodol were injected, followed by Gelfoam embolization as indicated. Thirty-seven patients (33 with cirrhosis) were treated. Sixty-nine cycles were delivered, with mean (+/-SD) Lipiodol and emulsified mitoxantrone doses of 11.3+/-3.8 ml and 11.8+/-5.2 mg, respectively. Thirteen, 16, and 8 patients received one, two, and three cycles, respectively, with time intervals of 123+/-60 days. Thirty patients received Gelfoam embolization at the first cycle, 9 at the second and 4 at the third. No treatment-related deaths occurred. Complications were mild and transient, including nausea/vomiting in most cases, fever over 38 degrees C 67%, pain 74%, ascites 8%, jaundice 3%, bleeding 3%, pancreatitis 3%, myelosuppression 44%, diarrhea 5%. Treatment response rate was 49% (including 16% minor responses) with 16% early progressions. With a median follow-up of 12 months, the 12-month response duration and survival rates were 56% and 79% respectively. Transcatheter chemoembolization with mitoxantrone appears to be a promising method for the palliation of advanced hepatocellular carcinoma, and deserves to be evaluated in well controlled randomized studies.

Antineoplastic Agents↗