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Biomedical subjects

C Ingvar

Publications and source records attributed to C Ingvar.

At least 55 records · Page 3Linked to original sources

Frequency and morphologic characteristics of invasive melanomas lacking specific surface microscopic features.

OBJECTIVES: To create a simple diagnostic method for invasive melanoma with in vivo cutaneous surface microscopy (epiluminescence microscopy, dermoscopy, dermatoscopy) and to analyze the incidence and characteristics of those invasive melanomas that had no diagnostic features by means of hand-held surface microscopes. DESIGN: Pigmented skin lesions were photographed in vivo with the use of immersion oil. All were excised and reviewed for histological diagnosis. A training set of 62 invasive melanomas and 159 atypical nonmelanomas and a test set of 45 invasive melanomas and 119 atypical non-melanomas were used. Images from the training set were scored for 72 surface microscopic features. Those features with a low sensitivity (0%) and high specificity (> 85%) were used to create a simple diagnostic model for invasive melanoma. SETTING: All patients were recruited from the Sydney (Australia) Melanoma Unit (a primary case and referral center). PATIENTS: A random sample of patients whose lesions were excised, selected from a larger database. MAIN OUTCOME MEASURES: Sensitivity and specificity of the model for diagnosis of invasive melanona. RESULTS: The model gave a sensitivity of 92% (98/107) and specificity of 71%. Of the 9 "featureless" melanomas the model failed to detect, 6 were pigmented and thin and had a pigment network. The other 3 were thicker, hypomelanotic lesions lacking a pigment network, some with prominent telangiectases, and all with only small areas of pigment. All featureless melanomas noted by the patients had a history of change in color, shape, or size. CONCLUSIONS: Surface microscopy does not allow 100% sensitivity in diagnosing invasive melanoma and therefore cannot be used as the sole indicator for excision. Clinical history is an important consideration when featureless lesions are diagnosed.

Algorithms↗

Chromosome analysis of 97 primary breast carcinomas: identification of eight karyotypic subgroups.

Chromosome banding analysis of 97 short-term cultured primary breast carcinomas revealed clonal aberrations in 79 tumors, whereas 18 were karyotypically normal. In 34 of the 79 tumors with abnormalities, two to eight clones per case were detected; unrelated clones were present in 27 (34%) cases, whereas only related clones were found in seven. These findings indicate that a substantial proportion of breast carcinomas are of polyclonal origin. Altogether eight abnormalities were repeatedly identified both as sole chromosomal anomalies and as part of more complex karyotypes: the structural rearrangements i(1)(q10), der(1:16)(q10;p10), del(1)(q11-12), del(3)(p12-13p14-21), and del(6)(q21-22) and the numerical aberrations +7, +18, and +20. At least one of these changes was found in 41 (52%) of the karyotypically abnormal tumors. They identify a minimum number of cytogenetic subgroups in breast cancer and are likely to represent primary chromosome anomalies in this type of neoplasia. Other candidates for such a role are translocations of 3p12-13 and 4q21 with various partner chromosomes and inversions of chromosome 7, which also were seen repeatedly. Additional chromosomal aberrations that give the impression of occurring nonrandomly in breast carcinomas include structural rearrangements leading to partial monosomies for 1p, 8p, 11p, 11q, 15p, 17p, 19p, and 19q and losses of one copy of chromosomes X, 8, 9, 13, 14, 17, and 22. The latter changes were seen consistently only in complex karyotypes, however, and we therefore interpret them as being secondary anomalies acquired during clonal evolution.

Breast Neoplasms↗

Is the use of sunscreens a risk factor for malignant melanoma?

The relation between use of sunscreens, different host factors and malignant melanoma was investigated in a population-based, matched case-control study of malignant melanoma in the South Swedish Health Care Region, which has the highest risk for melanoma in Sweden, between 1 July 1988 and 30 June 1990. In total, 400 melanoma patients and 640 healthy controls aged 15-75 years answered a comprehensive questionnaire regarding different epidemiologic variables, including questions on use of sunscreens and different constitutional factors. The use of sunscreens was not found to protect against developing malignant melanoma. Instead, an unexpected relation between the use of sunscreens and the risk of developing malignant melanoma was seen (odds ratio (OR) 1.8 for almost always vs never using sunscreens). A tentative dose-response relation was found. Virtually the same ORs were seen in both sexes. Furthermore, persons younger than 50 years had a higher OR than persons older than 50 years. When different melanoma presentation sites were considered, lesions of the trunk were associated with sunscreen use in females (adjusted OR = 3.7 for almost always vs never using sunscreens), while lesions of the extremity or head and neck were associated with sunscreen use in males (adjusted OR = 3.2 for almost always vs never using sunscreens). Raised naevi on the left arm and freckling were shown to be the major constitutional risk factors (OR = 3.9 for more than three naevi vs none and OR = 1.4, respectively). The results were essentially unaltered in a histopathologically re-examined material. Further investigations are needed in order to form a basis for melanoma prevention.

Adolescent↗

Induction of primary antigen-specific immune reponses in SCID-hu-PBL by coupled T-B epitopes.

Adoptive transfer of human lymphoid cells into immunodeficient (SCID) mice lacking the ability to functionally rearrange T- and B-cell receptor genes constitutes a unique model to study and manipulate human immunocytes. We have investigated this model for the purpose of generating an antigen-specific primary humoral immune response. Peripheral blood lymphocytes (PBL) derived from blood donors were used to repopulate SCID mice, which subsequently were immunized with different B-cell epitopes coupled to either tetanus toxoid (TT), or to a promiscuous helper epitope of TT, or by incorporating the antigens into a liposome construct. By recruiting the necessary T-cell help found in the T-cell memory compartment against TT, primary immune responses were obtained against the hapten dinitrophenyl (DNP), the V3 loop peptide derived from glycoprotein (gp120) (HIV-1), the melanoma-associated GD2 ganglioside and ovine submaxillary mucin. The primary immune response against the GD2 ganglioside was induced by incapsulating TT into GD2-containing liposomes. These liposome constructs also allowed us to induce a high human IgG serotitre (3000-4000) against this normally not very immunogenic ganglioside.

Animals↗

Dynamic Octreotide scintigraphy in neuroendocrine tumours.

The purpose of the present study was to investigate the optimal time for scintigraphy after injection of the radio-labelled somatostatin analogue, Octreotide. A secondary purpose was to evaluate the value of SPECT. One SPECT study and up to 4 whole body scans were performed in 22 patients with neuroendocrine tumours 0.5, 5, 24 and 48 hours after an injection of 110 MBq In-DTPA Octreotide. A total of 98 scintigrams were studied. A pathological uptake was found in 19 of the 22 patients. In 3 cases, early scintigrams (0.5 and 5 hours after injection) were of the most value whereas late scintigrams (24 and 48 hours) were the best in 4 cases. SPECT was found to be of value in 13 of 21 cases. For correct interpretation of Octreotide scintigraphy it is necessary to obtain both early and late scintigrams as well as a SPECT study.

Adult↗

Use of sunbeds or sunlamps and malignant melanoma in southern Sweden.

In a population-based, matched case-control study from the South Swedish Health Care Region, which has the highest risk for melanoma in Sweden, the relation between the use of sunbeds or sunlamps and malignant melanoma was investigated. Between July 1, 1988, and June 30, 1990, a total of 400 melanoma patients and 640 healthy controls aged 15-75 years answered a comprehensive questionnaire containing different epidemiologic variables. Questions regarding the use of sunbeds or sunlamps were included. The odds ratio for developing malignant melanoma after ever having used sunbeds or sunlamps was 1.3. Considering all age groups, the odds ratio was significantly elevated after exposure more than 10 times a year to sunbeds or sunlamps (odds ratio (OR) = 1.8). When the study was restricted to patients and controls younger than age 30 years because the use of tanning devices is much more common among young persons, the odds ratio was higher (OR = 7.7 for more than 10 times a year vs. none). These findings were independent of constitutional factors and factors regarding sun exposure. A dose-response relation was evident. Furthermore, among melanoma patients in this young age group, the ratio of females to males was significantly higher than in older patients. When different melanoma presentation sites were considered, only lesions of the trunk were significantly associated with sunbed or sunlamp use (OR = 4.2 for more than 10 times a year vs. none).

Adolescent↗

Cutaneous malignant melanoma in south Sweden 1965, 1975, and 1985. A histopathologic review.

BACKGROUND: There is an increase in the incidence of cutaneous malignant melanoma (CMM) among white people throughout the world. In Sweden, a fivefold increase has been recorded since 1960, but the mortality is rising at a much lower rate. Tumor thickness is the single most important prognostic factor for primary melanoma. This study aimed to clarify whether the thickness of the tumor in invasive CMM decreased during the period 1965-1985. METHODS: This population-based study identified 574 cases of CMM, both invasive and noninvasive, in the South Swedish Health Care Region in 1965, 1975, and 1985. Twenty-six cases were excluded because the collection or evaluation of the material was not possible. The remaining 548 cases were reviewed histopathologically, and a diagnosis of invasive CMM was rejected in 71 cases. Eventually, 467 cases of invasive melanoma remained in our study (70 in 1965, 124 in 1975, and 273 in 1985). The level of invasion, tumor thickness, regression, ulceration, presence of inflammatory cells, benign naevus cells, and the site of presentation were studied. RESULTS: The study found neither a significant decrease of tumor thickness of invasive CMM nor changes in the level of invasion or proportion of ulcerated melanoma. A significantly higher proportion of melanoma tumors containing benign naevus cells was seen throughout the years (P < 0.05). Women had significantly fewer inflammatory cells in their tumors than did men (P < 0.01). As expected, the anatomical site of presentation showed a significant sex-related difference, with more tumors on the legs of female patients and more on the trunk of male patients (P < 0.001). CONCLUSIONS: There is a divergence between the rapidly increasing incidence and the slower increase in mortality of CMM. This cannot be explained by a removal of the melanoma at a thinner thickness. Differences between the sexes according to the tumor site and the increasing rate of CMM containing benign naevus cells could implicate changes in the tumor biology. Public education in Sweden concerning ultraviolet radiation and the connection with melanoma is fairly new and might not have any influence on this time period. Additional investigation is needed to clarify this matter.

Adolescent↗

At what age do sunburn episodes play a crucial role for the development of malignant melanoma.

The age relationship between sunburns and malignant melanoma was investigated in a population-based, matched, case-control study from the South Swedish Health Care Region (the highest risk area for melanoma in Sweden). Between 1988 and 1990, a total of 400 patients with a first diagnosis of malignant melanoma and 640 healthy controls aged 15-75 years answered a comprehensive questionnaire including questions regarding ultraviolet radiation exposure. In addition, a literature review was performed. The average number of episodes of sunburn per year was significantly associated with malignant melanoma (relative risk, RR = 1.9 for > or = three episodes per year versus never). Outdoor employment during the summer was associated with a decreased risk for the development of malignant melanoma (RR = 0.8). Data from case-control studies and migration studies concerning age relationship between sunburns and melanoma are inconsistent. From our own data, we did not find a higher risk of melanoma developed in individuals who had experienced severe sunburns in childhood. Instead, a significantly increased risk was associated with sunburns after age 19 years, RR = 2.2 for a history of more than five times versus never. Even if the hypothesis is biologically plausible, that episodes of sunburn early in life are associated with a higher risk of melanoma, so far epidemiological evidence is scarce. There is a need for better prospective epidemiological studies addressing this issue.

Adolescent↗

Maximizing efficacy and minimizing toxicity in isolated limb perfusion for melanoma.

Isolated limb perfusion (ILP) with melphalan is an effective treatment for recurrent melanoma, but complete remission is achieved only in about 40% of patients. Regional toxicity is common, causing short-term disability and occasional longterm incapacity. Methods to maximize the efficacy and minimize the toxicity were investigated in 210 ILPs undertaken at the Sydney Melanoma Unit. Toxicity was found to be related to peak melphalan concentration, as well as to the area under the curve and maximum temperature. A dye dilution technique has been developed to measure perfusion circuit volume, so that a drug dose can be given to achieve an appropriate concentration. ILP with cisplatin was less effective and produced greater toxicity than ILP with melphalan; other drugs and drug combinations warrant investigation. Prophylactic ondansetron successfully controlled post-operative nausea and vomiting in most patients. Daily measurement of serum creatine phosphokinase (CPK) allowed early recognition of impending severe toxicity, with the greatest risk if CPK exceeded 1000 IU/l after the first post-perfusion day. Isolated limb 'infusion' (ILI) with melphalan, using percutaneously inserted catheters, is a much simpler procedure than ILP and has been found to be effective and easily repeated. The morbidity of ILP and ILI may be minimized by excluding the foot or hand with a rubber bandage.

Chemotherapy, Cancer, Regional Perfusion↗

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↗