PubMed HealthSearch

Biomedical subjects

C Ingvar

Publications and source records attributed to C Ingvar.

16 recordsLinked to original sources

Stapling in thyroid surgery. A prospective study.

In a prospective study, resection of the thyroid gland by means of a linear stapling device was compared with the conventional resection technique in 12 consecutive patients with thyreotoxicosis. The median time for resection of the stapled lobe was shorter than for the conventionally resected right lobe, although the difference was not statistically significant. The median preoperative bleeding during resection of the stapled left lobe was 42 ml (range 15-126 ml), compared with 78 ml (range 34-247 ml) during the conventional resection of the right lobe (P less than 0.05). Median postoperative bleeding was somewhat less from the stapled side compared with the conventionally resected side, but did not reach statistical significance. The study thus demonstrates the feasibility of carrying out resection of the thyroid gland with a linear stapling device. The technique minimizes peroperative bleeding. It could therefore be used in thyroid surgery.

Adult

Left handedness is uncommon in breast cancer patients.

Left handedness was found to be significantly less common among patients with breast cancer in southern Sweden (1.5%) than among a female referent population (5%) (P less than 0.0025). The findings lend support to theories suggesting that hormonal factors in early life are of importance both for handedness and for the risk of breast cancer.

Adolescent

Regional hyperthermic perfusion with melphalan after surgery for recurrent malignant melanoma of the extremities. Swedish Melanoma Study Group.

A prospective randomized trial testing regional hyperthermic perfusion with melphalan has been conducted. Sixty-nine patients with recurrent malignant melanoma of the extremities were randomly allocated to surgery (36 patients) or surgery plus regional perfusion (33 patients). Prognostic variables concerning primary tumor as well as the recurrent disease were evenly distributed in the groups, excluding any bias in the randomization. Median tumor-free survival after randomization was 17 months in the perfusion group and 10 months in the control group. There were 15 locoregional recurrences in the perfusion group and 24 in the control group. The tumor-free survival curve was significantly (P = .044) better for the perfusion group than for the control group. Median survival time after randomization was 57 months in the perfusion group and 35 months in the control group. This difference was not significant. One patient died within 1 month after perfusion of pulmonary embolism. Regional hyperthermic perfusion after surgery of recurrent malignant melanoma should only be recommended in prospective and controlled trials, until its value has been proven in several randomized studies.

Adult

Tumour uptake of monoclonal antibody after regional intraarterial injection. Biokinetics in the nude rat heterotransplanted with malignant melanoma.

Nude rats were heterotransplanted with human melanoma metastases on both thighs. Ten days later a bolus of 125I-labelled monoclonal antibody (MAb) 96.5 was injected through a catheter in the common femoral artery. The femoral vein was clamped for 15 min to obstruct the venous outflow from the injected leg. The specific tissue uptake (%/g) in the tumour on the injected side compared to the non-injected side showed initially higher uptake (ratio 7.2 at 3 h). After 24 h there were no side differences. The tumour to muscle ratio was 2.8 at 3 h when injected and control sides were compared. Intravenous or subcutaneous injection gave similar specific tissue uptake as regional arterial injection after 24 h. Tissue to plasma ratios were similar after intravenous and subcutaneous injection of monoclonal antibodies. Intraarterial injection of a bolus of labelled monoclonal antibodies and obstructing the venous outflow thus increased the tumour uptake during a short period of time during which the contrast enhancement was three-fold.

Animals

Radio-iodinated and internally labelled (35S) IgM monoclonal antibodies in a syngenic rat model.

To simulate the human situation concerning human monoclonal antibodies (MAbs), we have introduced a new syngenic rat model with an implanted rat colon carcinoma. Rat IgM MAbs (10B12), labelled by the chloramine-T method with 125I or internally with 35S, were injected intravenously into the rats and the biodistribution was studied for 8 days. The radioactivity uptake in the tumours of the 35S label was higher than that of the 125I label and the retention of 35S in the tumours gave tumour/blood ratios 8 times higher than those of 125I at 48 and 96 h after injection. In this model we have shown that dehalogenation of iodinated IgM MAbs is a serious problem. We therefore suggest that internally labelled MAbs should be used and that further investigations should be carried out in a syngenic rat model, since this probably reflects the clinical situation better than the nude mouse model.

Animals

Subcutaneous injection of monoclonal antibody 96.5. Biokinetics in the nude rat heterotransplanted with malignant melanoma.

Nude rats heterotransplanted with human melanoma metastasis were injected subcutaneously on the hind paw with 125I-labelled monoclonal antibody 96.5 and with control antibody 131I-OKT3. The elimination from the injection site followed a biexponential function. The uptake in the inguinal lymph nodes on the side of the injection was initially high, but after 90 h it equalled the control side. The uptake in the tumour was slower than after i.v. injection but higher than in other tissues except blood. More than 80% of the activity in the dissected liver represented circulating blood. The uptake ratio of 96.5/OKT3 was c.3 in the tumours but c. 1 in all other tissues including blood. The capillary filtration coefficient was proportional to the uptake in organs like liver, lungs and muscle. It is concluded that subcutaneously injected radiolabelled monoclonal antibodies are initially transported via the lymph but then mainly distributed via the blood reaching the different tissues including tumours.

Animals

Palliative surgery for brain metastases of malignant melanoma.

Forty patients with melanoma brain metastases were treated by surgery. Single brain metastases were found in 32 cases and multiple in eight. The most frequent tumor location was the frontal and frontoparietal lobes. Neurological improvement was observed in 25 patients and surgical mortality rate was less than 5%. The median survival time for all patients was 8 months. When patients with multiple cerebral metastases were excluded the median survival time was 13 months. The 3- and 5-year survival was 25% and 15%, respectively. Seventeen patients with extracerebral metastases received treatment and were without known extracerebral tumor at the time of brain metastases diagnosis. These patients had a median survival time that did not significantly differ from those without occurrence of extracerebral metastases. Quality of life as judged by Karnofsky index was improved after surgery and maintained on an acceptable level for the remaining time of survival.

Adult

Biokinetics of radiolabeled monoclonal antibodies in heterotransplanted nude rats: evaluation of corrected specific tissue uptake.

A tumor model is presented to study the biokinetics and localization of radiolabeled monoclonal antibodies (MAb) in the nude rat (Rowett RNu/RNu) heterotransplanted with human melanoma metastases. The nude rat is larger, less sensitive, and lives longer than the nude mouse. It is, therefore, well suited for in vivo studies of tumor localization with radiolabeled monoclonal antibodies. The tumor-to-host weight ratio was closer to the human situation for the nude rat than for the mouse, and quantitative imaging could be performed with a parallel hole collimator. We followed the antibody biokinetics for as long as 8 days, with repeated blood sampling and imaging. Specific uptake of MAb was higher in tumor tissue than in all other tissues except blood. Initial high uptake was also recorded in the bone marrow. The lymph glands showed a slow uptake of specific and control antibody. A simple in vitro correction procedure is described to calculate the corrected specific tissue uptake (STUcorr) that takes the blood activity into account. Thus it was shown that 80% of the tissue uptake in the dissected liver at 30 hr was due to labeled antibodies circulating in the blood. The specific tissue uptake ratio of antibodies 96.5 and OKT3 (nonspecific control) was unity for all other organs except for tumor tissue, where the ratio was greater than two and even higher when correction for blood content of labeled antibody was made.

Animals

Tourniquet infusion chemotherapy of the lower extremities--clinical and pharmacokinetic results.

A prospective analysis of tourniquet infusion chemotherapy is reported. Twelve patients with recurrent malignant melanoma and one patient with Kaposi's sarcoma on the lower extremities were treated. An objective tumor response (CR + PR) was noted in 4/8 patients with DTIC and in 1/5 with Adriamycin. Stable disease was registered in 2/8 and 2/5 when respective drugs were used. No major side effects were observed. Pharmacolkinetical analysis of Adriamycin were performed in five patients after two to three treatments. The plasma concentration time-curves of Adriamycin were in most cases described by an open three-compartment model. The AUC (area under the curve) values for Adriamycin were 3.4 (median value 95% CI 2.9-5.1) times higher than for Adriamycinol. The reproducibility of the intra-arterial techniques was established by the repeated pharmacokinetic analysis. This technique seems to give lower AUC (mg/m2) when compared with earlier published intravenous data. The results indicate that tourniquet infusion chemotherapy produces a reasonable response, and that further evaluation with other drugs and comparison with isolation hyperthermic drug perfusion will be of interest.

Adult

Southern travelling habits with special reference to tumour site in Swedish melanoma patients.

Southern travelling habits were recorded for 127 melanoma patients from southern parts of Sweden (the 56th latitude), 55 thyroid cancer patients, 100 non-Hodgkin's patients and 794 healthy controls from the same region. Melanoma patients were found to travel significantly more often south of the 45th latitude, as compared with patients with non-Hodgkin's lymphoma or thyroid carcinoma (RR = 2.2 for a difference of + 10 trips), and with the healthy controls (RR = 1.4 for a difference of + 10 trips). Considering men and women separately, the difference was significant only for men. Patients with melanoma had a higher educational level than the tumour controls and the healthy controls (p < 0.001 and p < 0.001 respectively). There was a significant correlation between high travelling frequency and high education. An increased risk related to southern travelling was present for patients with melanoma on the extremities and head and neck, as well as for patients with truncal melanoma. These findings support the concept that acute exposure to sunburn may be a risk factor for malignant melanoma.

Adult

Phase II study of high dose toremifene in advanced breast cancer progressing during tamoxifene treatment.

Thirty-five (34 evaluable) consecutive postmenopausal women with estrogen receptor positive (greater than or equal to 10 fmol/mg) or unknown advanced breast cancer were treated with high dose toremifene in a phase II study. All patients had progressed during prior adjuvant or palliativ antiestrogen treatment. The dose of toremifene was 240 mg per day. No complete or partial responders were registered. Nine patients (26%) were considered to have stable disease (NC). The time to progression for these patients was 5-27+ months with a mean time of twelve months and median time of eight months. Two patients are still on treatment after twelve and 24 months respectively. There seems to be a relationship with receptor value; however, there are two few patients for a safe statistical analysis. The side effects were insignificant. The conclusion is that the efficiency of toremifene as second line hormonal treatment is restricted, although it may be one additional choice.

Antineoplastic Agents

Tumour antigen heterogeneity within melanoma metastases--an evaluation by immunohistochemistry.

Fifty-eight metastases of malignant melanoma in 27 consecutive patients were evaluated by immunohistochemistry using monoclonal antibodies (MAb) 96.5, 48.7 and 4.2, all with a high specificity for melanoma tumour associated antigens. MAb OKT3 directed to human T-lymphocytes was used as control and normal mouse serum as background. Different degrees and patterns of staining were recorded using a scale of 0 to 4. 85% of the metastases were positive (score greater than +2) to 96.5 or 48.7 and 78% to antibody 4.2. All metastases were positive for at least one of the three antibodies, 93% for two, and 59% for all three antibodies. No substantial heterogeneity (more than +1 difference) was found in two sections approximately 5 mm apart within the same metastasis (one out of 39 metastases). In 15 patients in whom more than one tumour was examined, heterogeneity between individual metastases was found in one patient for antibody 96.5, three for 48.7 and none for 4.2. The existence of immunological heterogeneity in melanoma metastases must be taken into account when designing techniques for radioimmunoimaging and radioimmunotherapy.

Antibodies, Monoclonal

Estrogen receptor and binding site for estramustine in metastatic malignant melanoma.

Enzyme immuno assay (EIA) of estrogen receptor (ER) has confirmed the results of earlier investigations using steroid binding techniques, namely that ER is present at very low concentrations in samples from metastatic melanoma. Thirty-four of 61 samples (56%) were ER positive with EIA. The corresponding figures using isoelectric focusing (IF) for the steroid binding assay were 16 of these 61 samples (26%). The difference between the methods may be due to difficulties in the interpretation of analytical results for IF at low ER concentration levels or to interference from other 3H-estradiol binding components. Estramustine binding site (EMBS) has been found in samples from 15 of 77 patients (20%) with IF in polyacrylamide gels. Estramustine is, together with estramustine, the cytotoxic metabolite of estramustine phosphate (Estracyt). In analogy to the previously suggested therapeutic significance of estramustine binding protein in the treatment of prostatic cancer, the clinical importance of estramustine phosphate should also be studied in metastatic malignant melanoma in correlation with EMBS status.

Adolescent