First clinical experience with a high-capacity implantable infusion pump for continuous intravenous chemotherapy.

PURPOSE: To evaluate the efficiency of a new high-capacity pump for systemic venous chemotherapy and to verify the quality of implantation by interventional radiology staff. METHODS: A total of 47 infusion pumps with a 60-ml reservoir and variable flow rates (2, 6, 8, or 12 ml/24 hr) were implanted by radiologists in 46 patients with solid tumor metastases requiring treatment with a single, continuously infused cytostatic agent. The reservoir was refilled transcutaneously, usually once weekly. The flow accuracy of the pump was assessed from actual drug delivery recorded on 34 patients over a minimum observation period of 180 days. RESULTS: No early complications occurred in any of the 47 implants in 46 patients. A total of 12 (25.53%) complications occurred between 3 and 24 months after implantation. Seven (14.90%) of these were due to the external design of the pump, while five (10.63%) were related to the central venous catheter. In the 34 patients available for pump evaluation (follow-up of at least 180 days), the system was used for a total of 14,191 days (range 180-911 days, mean 417.38 days), giving an overall complication rate of 0.84 per 1000 days of operation. The mean flow rate accuracy was 90.26%. CONCLUSION: The new implantable pump showed good flow rate accuracy and reliable operation. The pump-related complications were related to its external design and have now been corrected by appropriate modifications. From a radiologic and surgical viewpoint, the venous implantation procedure is identical to that of conventional vascular access devices and can be performed by radiologists familiar with these techniques. The current limitations lie in the high cost of the pump and, for certain drugs, the short time between refills.

Morbidity and mortality after hepatic resection of metastases from colorectal cancer.

A review was carried out of morbidity and mortality after hepatic resection for metastatic colorectal cancer in 208 consecutive patients who underwent this procedure between 1980 and 1992. Overall postoperative morbidity and mortality rates were 35 and 2.4 per cent respectively. The major morbidity rate was 18 per cent, the main complications being intra-abdominal sepsis, biliary fistula and haemorrhage. Of the different factors examined, morbidity was significantly related to the extent of liver resection (53 versus 21 per cent after major and minor resections respectively), amount of blood transfused (18 versus 52 per cent for no transfusion and more than 300 ml transfused respectively) and the date of the operation (53 versus 24 per cent before and after 1986 respectively). Multivariate analysis showed that only the extent of hepatic resection and the period at which surgery was performed retained their statistical significance. These data support the opinion that surgical treatment of hepatic metastases from colorectal cancer is an effective procedure with acceptable mortality and morbidity rates. An extensive experience of hepatic surgery is, however, necessary to optimize results.

Continuous infusion with implantable pumps: expanding the radiologist's role.

Drug infusion systems attract increasing attention as biomedical technology offers miniaturized devices for targeted delivery of therapeutic substances on an outpatient basis. We have used a totally implantable, subcutaneous pump, externally programmable by radiofrequency link, learning the technique of implantation and management and using various imaging modalities for the diagnosis and control of complications. The procedure for implanting systems for continuous intrathecal analgesia and systemic intravenous chemotherapy is described. Our experience of the latter is made up of 296 implants in 290 patients. The selected infusion pump proved reliable and acceptable to patients and the quality of life, given the reduced drug toxicity, more than good. The complications were few both in frequency and in severity. The setting-up of a long-term infusion system, when major surgery is not needed, can fall within the interventional radiologist's field, partly because of a good cost-benefit ratio.

CT-fluoroscopy link-up (CTF): potential for special procedures.

Some interventional radiological procedures call for unrestricted axial vision and monoplanar fluoroscopy at different angles. We have mounted a fluoroscopic image intensifier in front of the gantry of a CT scanner to assess whether the combination would be useful. This link-up has been tested in a variety of situations and, even with the shortcomings of makeshift equipment, the combination filled some gaps in our vision of what is going on inside the patient, especially before an invasive procedure. It also proved useful in the planning of multiple procedures in a single session, especially when they had to be performed under general anesthesia in children or in the management of critical cases. We feel that the possibilities afforded by CTF (computed tomography plus fluoroscopy) need further exploration prior to the construction of purpose-built equipment. The interim information supplied suggests that it will be worth developing.

Circadian continuous chemotherapy of renal cell carcinoma with an implantable, programmable infusion pump.

The authors treated 42 metastatic renal cell carcinoma (RCC) patients who had received no previous chemotherapy or radiation therapy with circadian venous continuous infusion of 5-fluoro-2-deoxyuridine (FUDR). The drug was delivered by Medtronic Synchromed implantable pump (Medtronic, Inc., Minneapolis, MN) in 14-day cycles alternating with 14-day intervals of heparinized physiologic saline infusion. In the course of 24 months 444 cycles of therapy have been given for a total of 12449 days of pump function. Of the patients observed for at least 3 months (range, 3 to 23 months; median, 7 months) three showed complete response (7%; 95% confidence interval, 0% to 15%), three partial response (7%; confidence interval, 0% to 15%), 18 stable disease, and 18 showed progression. Eighteen patients, all with advanced disease at the time of implantation, were living 6 months after treatment started. Circadian continuous central venous infusion of FUDR is minimally toxic. The FUDR can be delivered safely and conveniently in this way for long spans. This therapy is as active as any currently available treatment, is administered in an entirely outpatient setting, and is associated with a normal quality of life.

Total parenteral nutrition prevents further nutritional deterioration in patients with cancer cachexia.

The effects of total parenteral nutrition (TPN) on some nutritional variables were prospectively investigated in 12 severely cachectic patients with advanced cancer. The following variables were determined before and at 5-day intervals during the 20-day administration of TPN: anthropometric indices (body weight, arm circumference, triceps skinfold, arm muscle circumference, arm muscle area, arm fat area, total body muscle mass); biochemical indices (total protein, albumin, cholinesterase, total iron binding capacity, thyroxin-binding prealbumin, retinol binding protein, urinary 3-methylhistidine and creatinine excretion, nitrogen balance); and peripheral lymphocyte count. TPN was delivered at 49.5 nonprotein kcal/kg-1/day-1 (80% as dextrose and 20% as fat) and amino acids 1.9 g/kg-1/day-1. A significant increase was obtained in body weight, triceps skinfold, arm fat area, and retinol binding protein. All remaining anthropometric and biochemical parameters did not show any significant positive or negative change, although nitrogen balance remained positive. No significant liver toxicity was apparent after the TPN period. It was concluded that although TPN is unable to completely reverse some nutrition-related variables in cachectic patients with cancer, most patients were kept within a normal range and some improved. Therefore, further deterioration of the nutritional state, which is characteristic of this phase of disease, was at least prevented.

Interventional radiology with venous port (chemotherapy and infusional support).

A completely portable permanent central venous access, consisting of a steel capsule sealed with a silicone membrane and connected to a silicone catheter (Port-a-Cath), was implanted in the subcutaneous tissue of 36 patients, most of whom no longer had accessible peripheral veins and needed to continue chemotherapy or undergo total parenteral nutrition. The access vessel was mostly the subclavian vein and the capsule was sutured to the pectoral fascia. Total subcutaneous implantation seems to afford optimum safety from infection and freedom for personal hygiene, produced no noteworthy complications and proved relatively simple to maintain.

"Nutritional" markers as prognostic indicators of postoperative sepsis in cancer patients.

A study was undertaken to identify the nutritional parameters associated with a high risk of postoperative sepsis. The nutritional status of 162 cancer patients subjected to clean or clean-contaminated elective surgery was preoperatively evaluated according to the following parameters: percentage weight loss, arm circumference, triceps skinfold, arm muscle circumference, creatinine-height index, total serum protein, serum albumin, total iron-binding capacity, cholinesterase, peripheral lymphocytes, complement C3-C4 components, and skin tests. Patients were followed postoperatively according to a precise protocol to classify them as infected or noninfected. Postoperative sepsis was present in 40 patients who had significantly different mean values for four nutritional parameters from those of 114 patients with no complications, ie, total serum protein, 6.60 vs 6.99 g/dl, p = 0.008; serum albumin, 3.39 vs 3.66 g/dl, p = 0.001; total iron-binding capacity 301.32 vs 337.17 mmg/dl, p = 0.006; and cholinesterase, 2389.77 vs 2770.10 mU/ml, p = 0.005. Moreover, the relative risk and the attributable risk for these variables were evaluated and the significance was tested by the chi 2 test. By using multiple logistic analysis it appeared that only total serum protein and total iron-binding capacity gave an independent contribution to the risk of postoperative sepsis, while serum albumin disappeared and cholinesterase became non significant when the contribution of the first two variables was accounted for. It was also possible to identify, in a small number of patients, combinations of two variables that were associated with a very high risk of postoperative sepsis.(ABSTRACT TRUNCATED AT 250 WORDS)

Subclavian venous thrombosis due to indwelling catheters: a prospective study on 52 patients.

Clinical occurrence of subclavian venous thrombosis due to indwelling catheters is rare, but there is some evidence that subclinical thrombosis frequently occurs. It is purpose of this study to report the results of a prospective investigation in patients with subclavian vein catheters. Fifty-two patients admitted to the Istituto Nazionale Tumori of Milan and candidate to infraclavicular percutaneous catheterization of the subclavian vein were evaluated. There were 26 polyvinyl chloride and 26 rubber silicone catheters, which were correctly positioned in the superior vena cava-atrium. Average duration of the intravenous stay was 12.8 days. Asymptomatic thrombosis was venographically demonstrated in 46.1% of the polyvinyl chloride catheters and in 11.5% of the silicone ones (p = 0.005). The average age of catheters with or without thrombosis was 10.8 and 13.8 days, respectively. Addition of heparin to the infusate (1 U/ml) did not reduce the thrombosis rate in polyvinyl chloride or in silicone catheters, but risk of thrombosis was significantly higher (p = 0.03) in polyvinyl chloride catheters without heparin in comparison to the silicone ones. Osmolarity of the infusional fluid, manipulation during the cannulation, colonization of the catheter tip, and duration of the intravenous stay of the catheter apparently did not influence the rate of thrombosis. Since the natural history of the thrombotic subclavian veins is not known, some caution must be paid to repeat the percutaneous cannulation of the same vein and the change the catheter over a guidewire.

Prevention and treatment of central venous catheter sepsis by exchange via a guidewire. A prospective controlled trial.

A new approach for preventing and treating sepsis due to central venous catheter (CVC) has been devised at the Istituto Nazionale Tumori of Milan. A prospective protocol has been developed that includes the weekly exchange of the CVC via a guidewire as well as its exchange when a CVC-related sepsis is suspected. Growth of microorganisms on the tip of the CVC is defined as contamination if peripheral blood culture is negative and as sepsis if it is positive for the same microorganism. Colonization simply means growth of microorganism independently of the results of peripheral blood culture. Two hundred seven CVCs (64 polyvinyl chloride and 143 rubber silicone) were evaluated in 62 patients, for a total of 170 exchanges. The incidence of colonization and sepsis was 33.8% and 4.8%, respectively, a rate which is not significantly different from the values found in 81 historical controls (30.8% and 11.1%). However, it is noteworthy that the sepsis rate was reduced strongly during the first month of observation (0% vs. 11.9%; p = 0.01), whereas in the second month, it was similar in both groups (15% vs. 7.1%). Moreover, it should be noted that three-fourths of the colonized CVCs became negative after the first exchange, and virtually all were negative at the fourth exchange. All of the episodes of sepsis resolved spontaneously with the CVC exchange. The study, therefore, concludes that this procedure: 1) is without risk for CVC cross contamination, 2) is effective in the treatment of contaminated CVCs and of septic patients without any interruption of total parenteral nutrition, and 3) can reduce the incidence of CVC sepsis during the first month of total parenteral nutrition. One must be cautious about the possible onset of pulmonary embolism in patients with subclavian venous thrombosis, since a transient pulmonary embolism occurred in one of the patients. With the use of silastic CVCs, which are less thrombogenic than polyvinyl ones, the rate of pulmonary embolism due to blind exchange (without previous venography) is estimated to be 0.1% to 0.2%.

Impact of cancer, type, site, stage and treatment on the nutritional status of patients.

This study analyzed the nutritional status of cancer patients in relation to type and site of origin of the tumor, stage of disease, and previous chemical or radiation therapy. The analysis was performed on 321 patients (280 with cancer and 41 controls). The nutritional parameters included per cent of weight loss, anthropometric indices (arm circumference, triceps skinfold, arm muscle circumference), creatinine-height index, serum protein, albumin, total iron binding capacity and cholinesterase, C3 and C4 components of complement, total peripheral lymphocytes, and skin tests. The statistical comparison between patients with different tumors and controls, between patients with different stages of the same tumor, and between patients treated with or without previous chemical or radiation therapy led to the following conclusions: 1) malnutrition is mainly related to the type and site of origin of the tumor and, in the early stages of disease, is more pronounced in patients with cancer of the esophagus and stomach; 2) except in patients with breast and cervix cancer, malnutrition gets more severe as the disease becomes advanced; 3) chemical or radiation therapy has a variable impact on the nutritional status, but in selected patients it causes a drop in body weight, arm circumference, arm muscle circumference, and peripheral lymphocytes; 4) body weight, cutaneous delayed hypersensitivity and serum albumin are the most commonly altered parameters.

Effect of supportive intravenous hyperalimentation on the nutritional status of cancer patients.

The effect of intravenous hyperalimentation on the nutritional status of 84 cancer patients treated at the Istituto Nazionale Tumori, Milan, has been evaluated. The body weight increased in 78% of patients, mid upper arm circumferance in 93%, triceps skinfold in 73%, mid upper arm-muscle circumference in 73%, creatinine/height index in 30%, serum albumin in 32%, transferrin in 35%, total peripheral lymphocytes in 38%. Lymphocyte blastogenesis increased in 74% of the patients examined and skin tests were converted from negative to positive in about 20% of patients. In addition 8 our of 18 patients responsive to IVH benefited from chemotherapy and/or radiotherapy indicating that the nutritional repletion of the host did not significantly affect the growth of the tumor. These findings support the opinion that neoplastic cachexia may depend partially on malnutrition and can be often reversed by IVH. Moreover, IVH might have an adjunctive role as potentiator of chemotherapy which however must be confirmed by clinical trials.