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D Civalleri

Publications and source records attributed to D Civalleri.

At least 19 recordsLinked to original sources

Anterior tension-free repair under local anesthesia of abdominal wall hernias in continuous ambulatory peritoneal dialysis patients.

BACKGROUND: A 10-year experience of abdominal wall hernia repair performed with anterior tension-free mesh or plug technique under local anesthesia in end-stage renal failure patients submitted to continuous ambulatory peritoneal dialysis (CAPD) is described in order to assess the safety and effectiveness of this approach. METHODS: Between January 1993 and December 2002, 18 hernia repairs were performed under local anesthesia in 16 patients (14 males and two females) with a mean age of 70 years (48-78). One umbilical and three unilateral inguinal hernias were observed and repaired before starting peritoneal dialysis (PD), while two umbilical, eight unilateral, and two bilateral groin hernias developed and were then treated during PD. Repairs were performed electively in all but one case, which was an emergency operation for strangulation. An ipsilateral scrotal swelling was also present in two indirect unilateral inguinal hernias. In these cases, the hernia sac was ligated before entering, while in the others it was simply dissected and inverted. RESULTS: Patients were discharged the same day or the day after surgery. No local or general immediate or late complications occurred. CAPD in subjects operated on during PD treatment was resumed the same day of surgery. In no instance was hernia recurrence or leak of dialysis solution observed at follow-up examinations. CONCLUSIONS: The absence of surgical and general complications and the nearly immediate resumption of PD indicate the anterior tension-free repair under local anesthesia as a safe and effective technique for CAPD patients even in an ambulatory or day-surgery setting.

Aged↗

Intraperitoneal mitoxantrone: a feasibility and pharmacokinetic study.

Fractionated doses have been advocated to prevent chemoperitonitis after intraperitoneal infusion of mitoxantrone. Patients with peritoneal carcinomatosis of various origin underwent surgery, including intestinal resections, with minimal residual disease. Peritoneal mitoxantrone in 1000 ml/m(2) saline was planned on the first post-operative day in groups of four patients (5 mg/m(2) for 3 and 5 days, 7.5 mg/m(2) for 3 and 4 days, 10 mg/m(2) for 2-4 days, if possible). Due to dose-limiting myelosuppression, only one and three patients received the 7.5-mg 4-day and 10-mg 3-day regimens, respectively. A total of 20 patients were consequently treated. Neither major complications nor severe pain were observed. Pharmacokinetics were completed on the 1st day in five 5-mg and five 10-mg patients, on the 5th day in three 5-mg patients, and on the 3rd day in one 10-mg patient. On the 1st day, mean peritoneal peak concentrations of mitoxantrone resulted 1.45 +/-0.56 (range 0.48-1.9) and 1.9+/-0.85 (range 1.27-3.13) microg/ml in the 5-mg and 10-mg patients, respectively. Mean dialysate/plasma exposure (AUC) ratio was 115. Even in patients with sutures, early post-operative fractionated intraperitoneal mitoxantrone appears feasible and safe, with a high local advantage, for up to 5 days of treatment and a maximum tolerated total dose of 20-25 mg/m(2).

Adult↗

Reduction of cisplatin nephrotoxicity by procainamide: does the formation of a cisplatin-procainamide complex play a role?

Procainamide protects mice bearing P388 leukemic cells against the toxicity of cisplatin without diminishing antitumor activity. The mechanism of action of procainamide protection was investigated both in vitro and in vivo. HPLC studies showed that procainamide forms a complex with cisplatin in vitro that has a UV spectrum similar to that of DPR, a triamine platinum complex that contains procaine as ligand. We report here the effect of the reaction product of cisplatin and procainamide on both cisplatin-induced DNA interstrand cross-links (ISCLs) and on the total DNA platination of isolated DNA. Total DNA platination in vitro of isolated DNA was increased by 113% (P <.01) and 17% (P <.05) after incubation times of 1.75 and 6 h, respectively, compared with products from the reaction of cisplatin with water. Furthermore, the reaction product of cisplatin and procainamide was bound to DNA to a significantly greater extent than was cisplatin itself. ISCLs were decreased by 41% when this drug combination was incubated with DNA for 1.75 h, but no changes were observed after incubation for 6 h. We also examined the influence of the time interval between administration of cisplatin and procainamide on normal kidney injury, the renal distribution and urinary excretion of platinum, and the formation of cisplatin-DNA adducts in renal tissue of Sprague-Dawley rats after i.p. administration of 7.5 mg/kg cisplatin either with or without procainamide. The plasma concentrations of urea and creatinine and kidney histology demonstrated that procainamide provided effective protection in vivo in the rat when administered either simultaneously or at 0.5 and 1 h before or after cisplatin. The protection was accompanied by both higher renal levels of platinum and cisplatin-DNA adducts and by an increase in the formation of ISCLs. Moreover, a dose-dependent reduction of urinary excretion and concentration of platinum was also observed. We propose that procainamide, after accumulation in the kidney, may coordinate with cisplatin to form a less toxic DPR-like complex that renders rats less susceptible to cisplatin-induced toxicity.

Animals↗

Pleural space perfusion with cisplatin in the multimodality treatment of malignant mesothelioma: a feasibility and pharmacokinetic study.

INTRODUCTION: Malignant pleural mesothelioma is an ideal model for testing new locoregional multimodality approaches because of its aggressive local behavior. METHODS: This study was planned to investigate the feasibility, safety, and pharmacokinetics of a multimodality therapy including an operation, pleural space perfusion (60 minutes) with cisplatin (100 mg/m2), hyperthermia (41. 5 degrees C), and postoperative radiotherapy (55 Gy to chest wall incisions). The effects of the extent of resection and perfusion temperature on cisplatin pharmacokinetics were evaluated. Ten patients with epithelial or mixed, stage I or II, malignant pleural mesothelioma underwent the following procedures: group A (3 patients), pleurectomy/decortication and normothermic pleural space antineoplastic perfusion; group B (3 patients), pleurectomy/decortication and hyperthermic perfusion; and group C (4 patients), pleuropneumonectomy and hyperthermic perfusion. Operations were selectively applied depending on tumor extent. Platinum levels were serially measured by atomic absorption in systemic blood, perfusate, lung, and endothoracic fascia. RESULTS: The overall procedure was completed in every case, without any death or toxicity. No lung damage was demonstrated after treatment. Major complications included 1 wound infection and 1 diaphragmatic prosthesis displacement. The mean peak platinum plasma levels were reached within 45 to 60 minutes after perfusion was started. Systemic drug concentrations were greater after pleurectomy/decortication than after pleuropneumonectomy (P =.006). The local tissue/perfusate ratio of platinum concentrations tended to be higher after hyperthermic perfusion rather than normothermic perfusion. CONCLUSION: This multimodality approach is feasible, pharmacokinetically advantageous, and safe enough to undergo further clinical investigations.

Adult↗

Differential device performances for hepatic arterial chemotherapy: a technical report on totally implantable pumps and ports for both continuous and bolus infusion.

Performances of totally implantable infusion systems were analyzed in patients with colorectal liver metastases undergoing intra-arterial treatment. It consisted of 14-day continuous infusion of 5-fluor-2'deoxyuridine with pumps (pump14, 44 patients) or ports fed by external pumps (port14, 34 patients), or bolus infusion of cisplatin (port21, 57 patients) or epirubicin (port7, 22 patients) every 3rd week and weekly, respectively. Toxicity and disease progression were the most common causes of treatment interruption. System failure occurred in 2 pump14, 9 port14, 6 port21 and 2 port7 cases. Pocket problems were most frequent in the pump14 group (30%), whereas catheter- and infusion-related problems were mostly observed in the port14 group (109%). The devices were still functional after 12 months in 92% of pump14, 24% of port14, 65% of port21 and in 78% of port7 patients. Although implantable ports allow adequate infusion periods, in most cases they appear especially suitable for bolus infusions.

Adult↗

[Performance and complications of totally implantable port device in bolus hepatic intra-arterial chemotherapy].

The performances of totally implantable ports were analyzed in patients with colorectal metastases undergoing intraarterial treatment. Seventy-nine patients received bolus infusion of Cisplatin (DDP, 57 cases) or Epirubicin (EPI, 22 cases) every 21 and 7 days, respectively. Disease progression or toxicity were the most common causes of interruption of treatment, whereas failure of ports occurred in six and two patients out of DDP and EPI groups, respectively. The incidence of single problems for each port was 65% in DDP group and 64% in EPI group, whereas rate of complications for each patient was 30% and 32%, respectively. The 12-months device duration rate in the two groups was 65% (median 17 months) in DDP group and 78% (median 18 months) in EPI group. The implantable ports employed for bolus arterial infusion, allowed adequate treatment periods in most cases, without any difference as far as intervals between cycles is concerned.

Aged↗

[Effects of adjuvant hyaluronidase in tumors refractory to chemotherapy. Review of the literature and pharmacokinetics of cisplatin after regional administration in animals and humans].

Several clinical studies have recently suggested that topical or systemic adjuvant hyaluronidase may increase the therapeutic index of anticancer drugs. In cases of disease progression, further objective responses have been observed after the association of hyaluronidase to the previously employed drugs. Some evidences suggest that hyaluronidase improves local diffusion as well as tissue and tumor uptake of the associated drugs. Hence, plasma and tissue concentrations of platinum following administration of cisplatin alone and associated with hyaluronidase have been investigated in 20 rats after intraperitoneal injection and in 10 patients with colorectal liver metastases and local progression of the disease after regional and systemic chemotherapy with intraarterial cisplatin and intravenous 5-fluorouracil. Three out of six refractory patients treated with hepatic intraarterial cisplatin + hyaluronidase showed one minor response and two stable diseases, respectively, without any apparent increase of treatment related toxicity. In turn, adjuvant hyaluronidase increased both the extent distribution and lasting time of cisplatin in the body and reduced plasma levels of total and free platinum originating from cisplatin, without any modification of either unbound fraction of platinum or total body clearance. Hence, adjuvant hyaluronidase seems to increase tissue extraction of cisplatin and, particularly, liver extraction after intraarterial administration in man. These results encourage further studies aimed to determine the clinical role of adjuvant hyaluronidase in patients refractory to regional chemotherapy.

Animals↗

[Severe infections after orthotopic hepatic transplant].

METHODS: The authors analysed severe infections in 43 consecutive patients undergoing orthotopic liver transplant. Prophylaxis and full anti-infection monitoring was performed in all cases. Immunosuppressive therapy was administered in the form of primary cyclosporine in 27 cases and primary OKT3 in 16 cases. RESULTS: Twenty-seven patients are still alive (median 8 months, range 2-40) and 16 died (median 22 days, range 10-92) of whom 4 without and 12 with infection, including two deaths owing to non-correlated causes with infection after recovery. Twenty-three patients underwent 33 episodes of severe infection (plus four with inconclusive positive cultures) without any case of protozoal or viral infection. All episodes occurred within two months of surgery and affected the lung (10), abdomen (7), lung + abdomen (1), urinary tract (1), lung + urinary tract (1), as well as two diffused cases and 7 cases of isolated bacteremia deriving from the donor (1), venous catheters (3), mild otorhinolaryngeal infection (1) and two unknown sources (2). Eighteen infective agents were identified in 45 cases. The bacteria involved in single-agent episodes were: 11 Gram+, 9 Gram- and five fungi. Polymicrobic and bacterial/fungal episodes were repeatedly observed in two and two cases. Postoperative renal insufficiency significantly influenced both the incidence of and mortality due to infection. Overall mortality was also influenced by early graft function, postoperative complications and reoperations, and the incidence of infections by the portal clamping stage, reject and prolonged coma. CONCLUSIONS: The absence of severe viral infections and the gradual reduction of mortality caused by infection appear to be parallel to the aggressive antiviral prophylaxis, the gradual improvement of intra- and postoperative management and primary immunosuppression with OKT3.

Adult↗

Screening study of abdominal aortic aneurysm in a general population: lipid parameters.

The level of blood lipids and apolipoproteins in subjects being screened for abdominal aortic aneurysms have been investigated. As part of an ultrasound screening programme in a population of 65- to 75-year-olds, blood samples were collected from 1460 of 1504 subjects with a normal aorta (97.1%) and 69 of 70 patients with an abdominal aortic aneurysm > 29 mm (99%). Samples were also taken from 22 of 27 patients (81%) with an ectatic aorta (26-29 mm). Total cholesterol, HDL-cholesterol, LDL-cholesterol, Apo-AI and Apo-B levels were significantly higher in women than in men (P < 0.01). Levels of HDL-cholesterol and Apo-AI were significantly lower in patients with an abdominal aortic aneurysm than in normal subjects (P < 0.001). The mean(s.d.) body mass index was 25.1(3.9) in women and 25.5(3.2) in men with aneurysms and not significantly greater than that of normal subjects (25.2(3.61) and 25.2(3.38) respectively).

Aged↗

Isolated lung perfusion with platinum in the treatment of pulmonary metastases from soft tissue sarcomas.

A multimodality approach including operation and isolated lung perfusion with platinum was used in six patients with lung metastases from soft tissue sarcomas. Staged thoracotomies were used in two patients with bilateral lesions. The inclusion criteria generally applied for surgical excision were adopted in this study. The pulmonary artery and a portion of the left atrium were isolated from systemic circulation and cannulated. The cannulas were then connected to a perfusion circuit and normothermic isolated lung perfusion was done for 60 minutes. The lung was then flushed and metastasectomy was done. Serial blood (systemic and pulmonary), tissue (normal lung and tumor), and urine samples were obtained for platinum content measurement by flameless atomic absorption spectroscopy. Lung damage was assessed by light and electron microscopy examination and by serial respiratory tests. Isolated lung perfusion was accomplished in all patients without any death, operative complication, or systemic toxicity. After operation, interstitial and alveolar edema developed in two patients (48 hours after treatment), necessitating respiratory support in one case. Total platinum concentrations in pulmonary plasma were about 43 times greater than those in systemic plasma. No differences in platinum concentrations between normal lung and metastatic tissue were found. Thus the proposed isolated lung perfusion technique is feasible and safe enough to be offered as a valid model to study combined chemosurgical approaches in the treatment of lung metastases.

Adult↗

Helical CT for the study of abdominal aortic aneurysms in patients undergoing conventional surgical repair.

OBJECTIVES: To evaluate the reliability of helical computed tomography (CT) as sole preoperative diagnostic technique for abdominal aortic aneurysms (AAA) and to compare these results with the surgical findings. MATERIALS: Thirty-three patients undergoing elective surgical repair. METHODS: Helical CT, Doppler exam of lower limbs, digital angiography, in case of peripheral vascular disease, and intraoperative evaluation. RESULTS: Helical CT correctly detected, in all cases, the proximal and distal extent of the AAA. The coeliac axis and its branches, the superior mesenteric artery and renal vessels as well as the inferior vena cava were always clearly depicted, showing anatomical variants or pathological involvement in 14 patients (42.4%). CONCLUSIONS: Helical CT can be used as the sole method for preoperative imaging of AAA. It allows a complete and precise evaluation of size, extent and relationship of the AAA, the surrounding vessels and other abdominal structures.

Aged↗

Pharmacological control of intimal hyperplasia in small diameter polytetrafluoroethylene grafts. An experimental study.

OBJECTIVE: The efficacy of a postoperative treatment with Low molecular weight heparin (LMWH) vs Ticlopidine in controlling early thrombosis, intimal hyperplasia and growth of true endothelial cells in small prosthetic expanded polytetrafluoroethylene (ePTFE) grafts (4 mm) interposed in the carotid artery of sheep has been evaluated. EXPERIMENTAL DESIGN: Thirty animals were randomized into three different groups: control group (CTRL); ticlopidine hydrochloride (TICL) 250 mg/b.d. by month for 4 weeks from day 1; LMWH 3,085 IU AXa s.c. preoperatively and once a day for the same period. RESULTS: Complete thrombosis of the graft occurred in 7 sheep in the CTRL group and 5 in the TICL group while 2 partial thrombosis were observed in the LMWH group (n.s.). In all the evaluable cases, hyperplasia was observed in both anastomotic areas and did not involve the middle portion of the graft. The mean +/- SD intimal thickness was 603 +/- 20 micron in the CTRL group, 356 +/- 10 in the TICL group and 152 +/- 17 in the LMWH group (p < 0.001) compared to the 60 +/- 12 of the normal intima. True endothlial cells were found mainly in the LMWH group close to the arterial anastomosis. CONCLUSIONS: The postoperative use of LMWH seems to inhibit intimal hyperplasia, with interesting results also on patency and cellular coverage. Further studies are necessary to support this promising trend.

Animals↗

Gemfibrozil and Mediterranean diet for patients with high plasma levels of lipoprotein [Lp(a)] and cholesterol--pilot study.

Plasma levels of lipoprotein-a [Lp(a)] > 30 mg/dl represent an independent risk factor for cardiovascular diseases with both proatherosclerotic and prothrombotic activity. The results of dietary or pharmacological treatment are not encouraging and are often controversial. We have evaluated a combination of medical treatment with Gemfibrozil (600 mg bid) and a Mediterranean diet for 2 months in 15 patients with both hypercholesterolemia (> 240 mg/dl) and high levels of Lp(a) (> 30 mg/dl). Three patients dropped out within the first 2 weeks, complaining of epigastric pain and burning; the remainder (5 females and 7 males, mean age 70 years) completed the treatment without any side effects. The median values of Lp(a) decreased from 36.5 to 8.4 mg/dl (p < 0.0002) and total cholesterol from 254.5 to 208.0 mg/dl (p < 0.0001). The small number of patients does not permit any definitive conclusion on effectiveness to be drawn, but the results indicate further randomized studies might prove worthwhile.

Aged↗

[Prevention of vascular intimal hyperplasia in small caliber prostheses. Preliminary results].

Intimal hyperplasia is one of the main risk factors for the patency of small diameter bypass grafts. The standard unfractioned heparin (UH) is able to control this phenomenon but the clinical use is not fit for long term treatment; on the other hand the antiplatelet drugs have an anti-thrombotic effect but they seem to be unable to control intimal hyperplasia. Low molecular weight heparins (LMWH) have an anti-thrombotic effect superimposable to that of UH with minimal side-effects and might inhibit intimal hyperplasia too. Based on these criteria, we carried out an experimental study on sheep with the aim of evaluating the efficacy of postoperative treatment with LMWH versus an anti-platelet drug in controlling intimal hyperplasia and growth of true endothelial cells in small prosthetic ePTFE grafts (4 mm) interposed in the carotid artery. At the operation, 30 sheep were randomly located in 3 groups: A = control group, no treatment; B = Ticlopidine hydrochloride 250 mg/bid by mouth for 4 weeks; C = LMWH 3.075 IU AXa (0.3 ml) sc preoperatively and then once a day for the same period. Complete thrombosis of the graft occurred in 7 sheep of group A, 5 in B and 2 partial in group C. The intimal hyperplasia was moderate-severe in group A, mild-moderate in group B and no-mild in group C. True endothelial cells were found mainly in the LMWH group; in the other groups and in other portions of the grafts the cellular coverage was accomplished almost completely by fibroblasts. The study is still in progress with 6 further sheep treated with LMWH.

Animals↗

Treatment of patients with irresectable liver metastases from colorectal cancer by chemo-occlusion with degradable starch microspheres.

Chemo-occlusion of the liver increases the tumour concentration of drugs. Thirty-nine patients with colorectal liver metastases received a monthly bolus administration of mitomycin C (10 mg/m2 on day 1) plus a continuous infusion of 5-fluorouracil (500 mg/m2 daily from days 1 to 5). Drugs were given via both portal (one-third of the dose) and arterial (two-thirds) routes to control large and small metastases. Arterially administered mitomycin C was mixed with individualized doses of degradable starch microspheres. In 16 patients treatment was not started or was interrupted early because of arterial or portal catheter problems. In 23 patients who received two or more cycles of treatment the mean(s.d.) microsphere dose was 835(399) mg. Toxicity was mild, consisting mainly of pain. Five complete and five partial responses were seen, and six patients had stable disease. The median time to progression and length of survival were 6 and 16 months respectively. The relatively high rates of complete and overall response in hypovascular tumours (six of 12 lesions) may support the rationale of chemo-occlusion.

Adult↗

Pelvic perfusion in the adjuvant therapy of locally advanced rectal cancer. Feasibility trial and initial clinical experience.

PURPOSE: The increased risk of pelvic recurrence in patients with locally advanced rectal cancer seems to justify a more aggressive regional therapeutic approach. In this attempt a feasibility study has been recently activated on hyperthermochemotherapeutic pelvic wash in patients with resectable, locally advanced, cancer of the distal rectum. METHODS: Two alternative methods of hyperthermochemotherapeutic pelvic wash have been used in sequence. In the first method 3000 ml of warm (45 degrees C) saline solution containing 30 mg of mitomycin C were injected into the pelvis both intraoperatively and in the immediate postoperative period. In the second method a 60-minute perfusion of the pelvic space with 2000 ml of heated (45 degrees C) saline solution with 40 mg of mitomycin C was provided intraoperatively using an extracorporeal circuit. RESULTS: Four patients submitted to abdominoperineal amputation with pelvic lymph node dissection have been treated following one of the two methods. No complications related to the treatment occurred. Either the first or the second hyperthermochemotherapeutic pelvic wash method showed a high regional pharmacokinetic advantage with a perfusate/blood "AUCs" ratio of 576 and 374, respectively. CONCLUSIONS: The potential role of hyperthermochemotherapeutic pelvic wash as an additional regional treatment in locally advanced rectal cancer and the differences between the two methods, in our limited experience, are discussed.

Aged↗

Bolus vs. continuous hepatic arterial infusion of cisplatin plus intravenous 5-fluorouracil chemotherapy for unresectable colorectal metastases.

UNLABELLED: A multicenter, randomized Phase 2 study that compared patients, affected by colorectal liver metastases, who received intrahepatic arterial infusion with two different schedules of cisplatin, bolus vs. continuous infusion, and systemic 5-fluorouracil. PURPOSE: The aim of this study was to validate results of a previous Phase 2 trial on bolus cisplatin intrahepatic arterial infusion, which reported a 47 percent response rate and a 32 percent 4-year survival rate for Gennari's Stage 2 patients, with a high rate of neurologic, gastrointestinal, and hematologic toxicity. METHODS: One hundred nine patients were randomized in a Phase 2 study to receive cisplatin intrahepatic arterial infusion (24 mg/m2/day, 1-->5, bolus vs. continuous infusion) and systemic intravenous 5-fluorouracil (250, 375, or 500 mg/m2/day, 1-->5; escalating doses, respectively, at cycles I, II, III, and VI). To avoid neurotoxicity a maximum of six cycles was administered. RESULTS: Preliminary results for the 78 evaluable patients are similar to those of the previous study: response rate 46 percent and at a median follow-up of 16.5 months, the overall survival was 16.5 months, with 45 percent of the patients who received more than 3 cycles alive at 3 years. Toxicity, evaluable in 99 patients, showed a decreased incidence of neurotoxicity and a tolerable gastrointestinal and hematologic toxicity, lower in the cisplatin continuous infusion arm. CONCLUSION: This study clearly shows that cisplatin intrahepatic arterial infusion is able to provide a good palliative effect with a tolerable toxicity.

Antineoplastic Combined Chemotherapy Protocols↗