Imaging with 131I-labeled monoclonal antibodies to a high-molecular-weight melanoma-associated antigen in patients with melanoma: efficacy of whole immunoglobulin and its F(ab')2 fragments.

In vitro experiments selected optimal conditions to radiolabel with 131I the whole immunoglobulin and F(ab')2 fragments of the monoclonal antibody (MoAb) 225.28S to a high-molecular-weight melanoma-associated antigen (HMW-MAA). Injection of the radiolabeled whole immunoglobulin and F(ab')2 fragments of the MoAb 225.28S into eight patients with melanoma resulted in the accumulation of radioactivity in 10 of 18 metastases. This localization is specific because of the close relationship between detection of HMW-MAA in lesions by immunohistochemical techniques and outcome of immunoscintigraphy and because of the different distribution in tumors and adjacent tissues of radiolabeled F(ab')2 fragments of MoAb 225.28S compared with 99mTc-pertechnetate and with radiolabeled F(ab')2 fragments of MoAb 4C4 to hepatitis B surface antigen. F(ab')2 fragments are superior to whole immunoglobulins to perform immunoscintigraphy, since they markedly reduce the background in bone marrow, liver, and spleen. The sensitivity of the procedure allows the detection of lesions with a diameter of at least 1.5 cm and is influenced by the level of the HMW-MAA in lesions and by their anatomical site.

Safety of absorbable suture for sternal closure after pulmonary or mediastinal resection.

The reliability of polyglyconate monofilament (Maxon) suture for sternal closure was tested on 216 consecutive sternotomies, performed on 208 patients in our department from January 1986 to December 1990. The reason of sternotomy was primary lung cancer in 34 cases (16%), lung metastases in 127 (59%), and disorders of the thymus in 55 (25%). Mean age was 38 years (range 3 to 78 years); multiple lung resections were performed in 102 patients (average 7 lesions, range 2 to 30); maximum extent of the operation was pneumonectomy in 2 cases, lobectomy in 53, segmentectomy in 27, and wedge resection in 74. Prior chemotherapy had been administered in 75 cases (35%). A second sternotomy was performed in 8 cases. No cases of sternal dehiscence, sternal infection, or empyema were observed, after a median follow-up of 27 months. Overall perioperative mortality was 0.9% (2/216). Our series demonstrates the safety of polyglyconate monofilament (Maxon) suture for sternal closure. Absorbable sutures appear to be a safe alternative to steel wire closure in patients undergoing extended pulmonary or mediastinal resection.

Pathogenesis and predictability of central venous catheter sepsis.

The purposes of this study were to analyze the causes and routes of infection of indwelling central venous catheters and to improve the diagnosis of catheter sepsis before the removal of the cannula. One hundred forty catheter tips were prospectively studies; also, cultures of 52 proximal segments of catheters, 44 swabs of the subcutaneous segment, 195 skin entry sites, 181 infusional fluids, 208 blood samples, and 106 infected distant sites were examined. The catheter sepsis rate was 7.6%, but this sepsis was primary in only 3.4%, because in 4.2% prior isolation of organisms from the wound, urine, throat, or sputum was possible, indicating that the catheter was not primarily responsible for the infection. Primary infection always disappears with removal of the cannula (with or without antibiotics), whereas the course of the secondary infection is related to the gravity of the infected foci and the involved microorganisms. Contamination of the infusional fluid, the skin entry site, and some distant foci carry a real risk of seeding the catheter (from 5.8% to 19.5%). The cultures of the skin entry sites, infusional fluids, distant foci, and the subcutaneous segment of the catheter did not prove useful in predicting the infection. Only the blood cultures were a reliable diagnostic tool: a positive blood culture meant colonization of the catheter tip in 44% of cases and sepsis in 36%. Although the potential colonization varied greatly for different microorganisms, the growth of microorganisms in the blood was a strong indication for removing the cannula.

Central venous catheter sepsis: prognosis and treatment.

The purpose of this study was to evaluate the prognosis of patients with central venous catheter (CVC) sepsis, with particular reference to two therapeutic procedures, 1) CVC exchange over a guide wire and 2) removal of the catheter An evaluation was made of the clinical records of 22 cancer patients receiving total parenteral nutrition because of severe malnutrition and of 27 CVC-related septic episodes defined as growth of the same microorganism on the CVC and in peripheral blood. Bacteriological findings included Candidae n = 17, S albus n = 4, E Cloacae n = 4, Enterococcus n = 1 and P aeruginosa n = 1. In 22 cases the CVC was exchanged and in five cases it was removed on the clinical suspicion of CVC-related sepsis. Nineteen of the 22 patients had their blood culture rendered negative with CVC exchange and in three of the other five patients it was resolved bacteriologically after removal of the CVC. There was no clear effect of the CVC sepsis on the final outcome of the patients' illness. In fact, seven patients eventually died because of reasons apparently unrelated to the CVC sepsis-which had bacteriologically and clinically resolved-and seven patients recovered and were discharged in good condition despite the initial failure of CVC manipulation. The conclusion reached was that death should not occur as a result of CVC sepsis, provided this is properly identified and adequately treated. Since CVC change allows earlier recognition of the complication and effective treatment, it may be considered the therapy of choice in the management of suspected CVC sepsis.

Blood culture as a guide for the diagnosis of central venous catheter sepsis.

The purpose of this study was to evaluate the predictability of peripheral (PBC) and central blood cultures (CBC) in the diagnosis of central venous catheter (CVC) sepsis (growth of the same microorganism in the peripheral blood and on the catheter tip). The contamination and sepsis rate of 256 CVCs and the relationship with PBC and CBC was evaluated in a series of cancer patients included in a prospective protocol on CVC infections at the Istituto Nazionale Tumori of Milan. Overall CVC contamination was 10.5% and sepsis rate was 3.1%. The positive predictive value for CVC sepsis was 46.7% for positive PBC + CBC, 38.1% for positive PBC and 16.6% for positive CBC. The small gain in the predictive positive value obtained with the use of PBC and CBC and the slight increase in the specificity does not justify, in our opinion, the use of both these parameters for the diagnosis of CVC sepsis.

Management of lymphatic fistulas by total parenteral nutrition.

Lymphatic fistula is a rare surgical complication, which mainly occurs after cervical or retroperitoneal lymph node dissection and which frequently requires a surgical repair. A small series of nine postoperative lymphatic fistulas treated conservatively with total parenteral nutrition (TPN) is reported. All the patients were malnourished at the beginning of the TPN, and all exhibited an objective improvement of their nutritional status after completion of the treatment. Due to the interruption of the enteral alimentation or to the nutritional repletion, spontaneous closure of the fistula was achieved in eight of nine patients treated with TPN longer than 1 week. The authors conclude that whenever the immediate surgical repair is not recommended, or it is not successful, a 2- to 3-week course of TPN may be used with the chance of spontaneous healing. In any case, patients conservatively treated by TPN can undergo a delayed operation with minimal risk because of the improved nutritional status.

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.

Hypocupremia in patients receiving total parenteral nutrition.

Although hypocupremia is a well-known consequence of long-term total parenteral nutrition (TPN), its incidence as well as the duration of TPN necessary to induce it are still unsettled. The purpose of this study is to review the changes in serum copper level in 25 patients receiving TPN for a period longer than 2 wk (mean duration 6 wk) at the Istituto Nazionale Tumori of Milan and to evaluate the possible relationship of cupremia with the basic disease. Main indications for TPN included enterocutaneous fistulas (11 patients), cancer cachexia (10 patients), radiation enteropathy (two patients), and severe postoperative stricture following esophagogastric resection (two patients). Mean value of serum copper at the beginning of the study was 143 micrograms/100 ml (normal value 65-165 micrograms/100 ml), and the regression analysis showed a mean fall of 5.64 micrograms/100 ml/wk. Hypocupremia occurred in four patients (three with intestinal fistulas and one with radiation obstructive enteritis) at 5th, 6th, 9th, and 6th wk of TPN, respectively. No patient with cancer cachexia developed hypocupremia. No patient with hypocupremia had clinical evidence of a copper deficiency syndrome. We conclude that 1) hypocupremia does not occur within the first month of TPN; 2) its incidence is about 16% in patients intravenously fed for period longer than 2 wk; 3) it is more frequent in patients with enterocutaneous fistulas, whereas it never occurs in patients with cancer cachexia, and 4) it is not necessarily associated to a clinicometabolic syndrome of copper deficiency. Finally, the "nutritional" meaning of serum copper should be questioned in cancer patients since it could represent a "tumor marker."

"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)

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.

Evaluation of toxic effects following administration of monoclonal antibody MBr1 in patients with breast cancer.

Twelve patients with disseminated breast cancer were injected with monoclonal antibody MBr1 at the National Cancer Institute of Milan, Italy, from January 1983 to March 1985. The first seven patients had advanced disease and the remaining five operable breast cancer. In the first seven patients the initial dosage of MBr1 was 0.5 mg and was doubled in the next patient up to 16 mg. The last five women received 10 mg of MBr1. No general side effects such as bronchospasm, hypotension, immediate or delayed allergic reactions were observed. Four patients who were injected with 10 mg or more experienced fever, shudder and vague abdominal and articular pain. The following tests were monitored: R.B.C., W.B.C., percentage of lymphocytes, blood glucose, urea nitrogen and creatinine, serum levels of Na+, K+, Cl-, total proteins levels, albumins and globulins, bilirubin, GOT, GPT, alkaline phosphatase, LDH, amylase, gamma GT and CPK. No major modifications were observed: a limited increase of the transaminases, LDH and gamma GT was evident at the last check. An early temporary alteration of CPK was observed in the four patients who had symptoms. Serum levels of MBr1 are detectable immediately after injection starting from 4 mg, and all sera were negative 48 hours later. It is concluded that the scanty toxicity allows to continue clinical investigations to verify the linkage between MBr1 and Ca-MBr1 "in vivo" after a single injection of no more than 16 mg of the MoAb. The increase of this dosage as well as multiple injections do not seem safe at present.

[Parenteral hyperalimentation in patients with advanced neoplastic disease (author's transl)]. / Iperalimentazione parenterale nei pazienti con neoplasia avanzata

Two groups of patients suffering from advanced neoplastic disease were fed parenterally for a period ranging from 1 to 16 weeks. The parameters considered were: weight change, serum albumin level, lymphocyte transformation test and serum immunoglobulin level. There were 23 patients in one group and 21 patients in the other. Regimens included for group I: saline solution (1000-1500 ml), glucose (100-150 g) and amino acids (15-30 g) per day; for group 2: 40-50 Cal/kg per day (dextrose about 15 g/kg per day), about 2 g of amino acids/kg/day and about 40-50 ml water/kg/day. In addition, 13 patients underwent both treatments sequentially. All the Group I patients lost weight (1.3 kg/week); while out of 23 patients in Group 2, 15 gained weight, 2 remained unchanged and 6 continued to lose weight, but to a lesser rate than before hyperalimentation (the average weight gain was 1.1 kg/week). Serum albumin levels decreased in 19 out of 25 patients in Group I and increased in 14 out of 26 patients of Group 2. Initial values of the lymphocyte blast transformation test were very low in both groups of patients, and an increase was observed only in patients treated by hyperalimentation. The increase was more evident in patients who were not under antiblastic treatment. Changes in serum immunoglobulin levels were not significant. The authors conclude that malnutrition plays a very important role in neoplastic cachexia and can be improved by parenteral hyperalimentation. Although it is possible that in the near future hyperalimentation and conventional neoplastic therapies will play complementary roles in treatment of advanced neoplastic disease, malnutrition is still the specific indication for intravenous hyperalimentation.

Anti-melanoma monoclonal antibody 225-28S: evaluation of toxicity in man.

To investigate possible undesirable effects due to the intravenous administration of a reagent of a xenogenic nature (monoclonal antibody 225-28S) in man, a toxicologic study was carried out on 85 patients with metastatic cutaneous melanoma. Two reagents were tested in this study: purified monoclonal antibody (MoAb) 225-28S and its F(ab')2 fragment. Purified MoAb was labelled with 131I and F(ab')2 fragment with 131I, or 123I, or 111In or 99Tc. The quantity of MoAb or F(ab')2 injected ranged from 14 to 750 micrograms, and the specific activity from 37.0 to 2116.4 MBq/mg. The total radioactivity injected varied from 25.9 to 891.7 MBq/mg. In addition to a careful clinical examination, the following tests were done to monitor possible adverse effects: blood glucose, azotemia, RBC, WBC, platelet count, serum creatinine, creatinine clearance, plasma electrolyte levels, serum proteins, albumin/globulin ratio, serum bilirubin, SGOT, SGPT, gamma GT, and CPK. These tests were done before the injection and on days 7 and 14. No patient experienced adverse general effects like fever, nausea, vomiting or allergic reactions. None of the aforementioned hematometric and biochemical tests showed significant variations compared with the initial values. It is concluded that a single injection of these reagents at the dosages tested is completely atoxic.

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.

Restatement of lymphography in childhood: experience with 413 consecutive patients in ten years.

From January 1969 to June 1978, 413 children under 15 years of age underwent lymphography at the Istituto Nazionale Tumori of Milan. Successful lymphatic cannulation was accomplished in 97.7% (769/787) of the sites where it was attempted. No major or permanent complications were encountered. In those children undergoing biopsy of opacified lymph nodes, the lymphographic-histologic correlation was 94.5% (104/110). This study has shown that lymphography in childhood can be as readily performed as in the adult and that its diagnostic accuracy is acceptable. As in adults, it is useful in treatment planning, evaluating results of therapy, and detecting a recurrent tumor.

Lymphography in childhood: six years experience with 242 cases.

From January, 1969 - December, 1974, 242 children less than 15 years of age underwent lymphography at the National Cancer Institute, Milan. Successful lymphatic cannulation was accomplished in 97% (440/463) of the sites where it was attempted. No major or permanent complications were encountered, although minor untoward effects might not have been recorded. In those children undergoing biopsy of opacified lymph nodes, lymphographic-histologic correlation was 98% (45/46). Nonspecific reactive hyperplasia lymphographic patterns were encountered in 36% of all studies, confirming its high incidence in the pediatric age group. This study has shown that lymphography in childhood can be as readily performed as in the adult and that its diagnostic accuracy is acceptable. As in adults, it is useful in treatment planning, evaluating results of therapy, and detecting recurrent tumor. The frequent occurrence of nonspecific reactive hyperplasia in the pediatric lymphogram should not be mistaken for evidence of tumor, particularly lymphoma.