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J Lindholm

Publications and source records attributed to J Lindholm.

At least 37 records · Page 2Linked to original sources

Cytological diagnosis of bone tumours.

We evaluated the diagnostic accuracy of fine-needle aspiration biopsy in a prospective study of 300 patients with previously undiagnosed bone lesions. Patients with suspected local recurrence of a primary bone tumour or a metastatic lesion of a previously diagnosed malignancy were excluded. Fine-needle aspiration biopsy was performed under radiological control as an outpatient procedure. The series was grouped into three major categories: 1) benign bone lesions including infections; 2) primary malignant bone tumours; and 3) metastases including lymphomas and myelomas. We compared the cytological diagnosis with the final diagnosis as assessed by histological examination and/or the clinical and radiological features. Material considered conclusive for cytological diagnosis was obtained from 251 of the 300 patients. Of the 49 failures, there were 24 aspirates with insufficient cellular yield and 25 in which a diagnosis could not be made although the cytological material was adequate in quantity. Most of the inconclusive aspirates (36/49) were obtained from benign bone lesions. The diagnosis was correct in 239 (95%) of the 251 cases providing adequate cytological material. There were eight (3%) falsely benign diagnoses, one (0.3%) falsely malignant, and three cases in which we were unable to differentiate between sarcoma and a metastasis. Chondrosarcoma (2/12) gave the greatest diagnostic difficulty and Ewing's sarcoma the least (0/9). There were no decisive errors of treatment. All falsely benign or malignant diagnoses were questioned, and led to open biopsy since they did not correlate with the clinical and radiological features. Our study suggests that fine-needle aspiration biopsy is a valid option for the diagnosis of bone tumours. It is a simple outpatient procedure which gives sufficient cytological material for the correct diagnosis in 80% of cases. As with histological analysis of material from open biopsy, the cytological assessment must agree with the clinical and radiological findings.

Adolescent↗

Reproducibility of subjective immunoscoring of steroid receptors in breast cancer.

OBJECTIVE: To evaluate the reproducibility of subjective immunoscoring of steroid receptors in breast cancer by inexperienced observers after brief training by one experienced observer. STUDY DESIGN: Thirteen inexperienced observers were trained for a few minutes semiquantitatively (0-4) to score tumor nuclei in two breast cancer frozen sections immunohistochemically stained each for estrogen or progesterone receptors. Then, the fractions of 0, 1, 2, 3 and 4 "stained" nuclei were estimated individually. Thereafter, the experienced observer pointed out the nuclei one by one, and the participants scored these nuclei individually. From these data, histoscores were calculated. RESULTS: When comparing individual scorings (n = 1,320) with the gold standard, discrepancies occurred mainly between scores 2 and 3, and the best concordance was achieved for the scores 0 and 4. For the histoscores, coefficients of variations for the estimated scores (7.3-33.7, mean 17.2) were systematically higher than those derived from nucleus-by-nucleus scoring (2.6-15.4, mean 10.3). CONCLUSION: Inexperienced observers can be trained quickly to arrive at fairly reproducible histoscores for immunohistochemically stained estrogen and progesterone receptors in breast cancer frozen sections. Nucleus-by-nucleus scoring seems to be more reproducible than estimating fractions of nuclei with certain positivity and should be recommended in cases of values close to the decision threshold.

Breast Neoplasms↗

Combined use of nuclear morphometry and DNA ploidy as prognostic indicators in nonresectable adenocarcinoma of the pancreas.

The introduction of combined modality treatment has only marginally affected the prognosis in nonresectable pancreatic carcinoma. Evaluation of easily accessible prognostic variables could be of clinical importance when selecting patients for proper therapy. DNA ploidy and morphometric variables were chosen as prognostic markers and assessed on cytologic material obtained by fine-needle aspiration biopsy (FNAB) from 128 patients with pancreatic carcinoma. The nuclear DNA content was measured by image cytometry. Patients were categorized as short-term (< or = 6 mo) and long-term survivors (> 6 mo). Ninety-eight of 116 nonresectable patients were possible to evaluate. There were significant differences between short- and long-term survivors with regard to DNA ploidy (p < 0.01) and the morphonuclear variable anisokaryosis (p < 0.001). In patients with either DNA aneuploid tumors or anisokaryosis > or = 0.6, the survival time was 6 mo or less in 85 and 93%, respectively. When both these criteria were fulfilled, only 5% survived for more than 6 mo. Thus, DNA ploidy and morphometry, separately or in combination, may provide prognostic information in nonresectable pancreatic carcinoma.

Adenocarcinoma↗

Near-haploidy in two malignant fibrous histiocytomas.

Cytogenetic analysis of two malignant fibrous histiocytomas (MFH) revealed near-haploid clones in both tumors. One tumor had only 23 chromosomes, the lowest chromosome number so far detected in human neoplasia, and showed several structural rearrangements: 23, X, der(1)t(1;?;8)(q42;?;q13), +del(7)(p11),der(8)t(8;13)(q13;q12), inv(9)(p24q21), r(10)(p15q26), -13, der(14)t(14;22)(p13;q11), -15, +r. The other MFH had only numerical changes: 28,X, +5, +18, +20, +21, +22/56, idemx2. With the present two cases, four of 78 MFHs studied in our laboratory have been near-haploid, suggesting that this otherwise rare phenomenon in neoplasia may be relatively common in MFH.

Female↗

Low risk of recurrence of enchondroma and low-grade chondrosarcoma in extremities. 80 patients followed for 2-25 years.

We analyzed the clinical course in 40 patients with enchondroma and 40 with low-grade chondrosarcoma of the extremities after a median follow-up of 7 years. 13 patients with enchondroma and 2 with chondrosarcoma had only open biopsy and they had no signs of further progression of the lesions. Among 23 patients with enchondroma and 23 with chondrosarcoma who were treated by intralesional curettage, 3 had local recurrences. The 10-year local recurrence rate was 0.04 in the enchondroma group and 0.09 in the chondrosarcoma group. There were no metastases. The results imply that enchondroma and low-grade chondrosarcoma of the extremities should be treated with limited surgery. The morbidity associated with en bloc resection and reconstruction can apparently be obviated without jeopardizing the limb or survival.

Adolescent↗

Nuclear DNA content, proliferating-cell nuclear antigen (PCNA) and p53 immunostaining in predicting progression of laryngeal cancer in situ lesions.

Squamous epithelial cancer in situ (CIS) of the upper aerodigastric tract is a histopathologically well-defined condition. However, in clinical practice, morphological grading of dysplasia is difficult and shows large variability. The biology of CIS remains enigmatic, and there is yet no reliable way to predict whether a CIS lesion will progress to invasive cancer, remain stable or regress. In the search for markers able to foretell clinical outcome, we performed image DNA cytometry (ICM) and immunohistochemical staining for PCNA as well as p53 in 38 laryngeal CIS lesions, of which 9 progressed to invasive cancer. The majority of the CIS lesions displayed high-grade DNA aberration, a high PCNA-positive rate, and every third lesion was p53-positive by immunostaining. The lesions which progressed to invasive cancer showed a clear tendency towards more pronounced DNA aberration, a higher percentage of intense PCNA staining and more frequent p53 positivity. By combining the results from the analyses of DNA, PCNA and p53 in a prognostic index for each individual case, we correctly classified 82% of the lesions as progressors or non-progressors.

Adult↗

Clonal structural chromosome aberrations in fibrous dysplasia.

Cytogenetic analysis of short-term cultures from a case of monostotic fibrous dysplasia in a 14-year-old girl revealed multiple clonal structural rearrangements with evidence of clonal evolution. The karyotype was 46,XX,del(3)(q27),add(10)(q22),add(12)(p13)/46,idem,t(3;8)(p21;q13 ),add(10) (q26),der(15)del(15)del(15)(q15q22)ins(15;?) q15;?)/46,id em,-X,+2,t(3;8),add(10),der(15). The finding of clonal structural aberrations suggests that fibrous dysplasia is a neoplastic lesion which develops as the result of somatic mutations.

Adolescent↗

Morphometric, DNA, and proliferating cell nuclear antigen measurements in benign melanocytic lesions and cutaneous malignant melanoma.

Morphometric, DNA, and proliferating cell nuclear antigen (PCNA) measurements were taken of benign melanocytic tumors and malignant melanomas. Significant differences between lesion groups according to Krushell-Wallis analysis were found in terms of mean nuclear area, coefficient of variation (cv) of nuclear area, cv of nuclear shape nuclear contour index (NCI), mean and cv of nucleolar area, DNA 2.5 c and 5 c exceeding rates, and PCNA positivity. A logistic regression analysis with respect to banal nevi versus primary malignant melanoma showed that the cv of nuclear area and the DNA 2.5 c exceeding rate were significant independent predictors. Nuclear polymorphism, i.e., the cv of nuclear shape NCI, was larger in metastasizing primary melanomas than in thin nonmetastasizing primary melanomas. PCNA positivity was occasionally increased in keratinocytes adjacent to nevi or melanomas. Larger values for nuclear area, DNA aneuploidy, and PCNA positivity were found in thick malignant melanomas and melanoma metastases than in benign melanocytic lesions and thin malignant melanomas. Morphometry, DNA content, and PCNA positivity thus seem to reflect different stages in tumor progression of malignant melanoma.

Adolescent↗

The ratio between serum levels of insulin-like growth factor (IGF)-I and the IGF binding proteins (IGFBP-1, 2 and 3) decreases with age in healthy adults and is increased in acromegalic patients.

OBJECTIVE: Several in-vitro studies have suggested that the biological actions of IGF-I can be modified by the presence of specific IGF binding proteins. In man, the 24-hour serum levels of IGF-I and IGFBP-3 remain constant, but short-term changes in the IGF-I/IGFBP-3 ratio have been described following GH administration. Serum levels of IGF-I and IGFBP-3 decrease with age in normal adults and are elevated in active acromegaly due to excessive GH secretion. However, the individual ratios between serum levels of IGF-I and IGFBP-3 in acromegalic and healthy adults have not been described previously. METHODS AND MATERIALS: We studied this ratio in 198 healthy adults and in 56 acromegalic patients, grouped according to their serum GH levels (group I GH < 2mIU/l II GH 2-10 mIU/l; III GH > 10 mIU/l). In all subjects a single blood sample was drawn for IGF-I, IGF-II, IGFBP-1, IGFBP-2, IGFBP-3 and GH measurements by specific RIAs. In 38 of the patients a 24-hour urinary collection was performed for GH determination. RESULTS: In healthy adults serum levels of IGF-I and IGFBP-3 decreased with increasing age (r = -0.52 and r = -0.34, respectively, P < 0.0001). In addition, the molar IGF-I/IGFBP-3 ratio declined with increasing age (r = -0.44, P = 0.0001). In patients with acromegaly and high serum GH levels (group III), circulating IGF-I was increased 7.97 standard deviations (SDS) and IGFBP-3 was increased 4.20 SDS (P < 0.0001). Serum levels of IGF-II were normal in all three groups (588 +/- 240 micrograms/l) whereas IGFBP-1 and IGFBP-2 levels were low and IGFBP-2 levels decreased significantly with increasing serum GH levels (P < 0.0001). The molar IGF-I/IGFBP-3 ratio in the acromegalic patients was significantly higher than in the controls (P < 0.0001) and correlated significantly with urinary GH excretion (r = 0.67, P < 0.0001) as well as with serum GH levels (r = 0.73, P < 0.0001). CONCLUSION: We demonstrated a decreasing molar IGF-I/IGFBP-3 ratio with increasing age in healthy adults and an increased ratio between serum IGF-I and IGFBP-3 levels in acromegalic patients. As IGF-II is normal and IGFBP-1 and IGFBP-2 are inversely correlated to the serum GH levels in the acromegalic patients, we speculate that the molar ratio between IGF-I and IGFBP-3 reflects free (biologically active) IGF-I and is dependent on GH levels.

Acromegaly↗

Morphometric characteristics in adenocarcinoma of the pancreas and chronic pancreatitis.

BACKGROUND: Morphometric analysis whereby size and form of cellular nuclei are transformed into quantities has previously been shown to be a valuable adjunct to the histopathologic differential diagnosis between chronic pancreatitis and pancreatic carcinoma. The present study aims to assess the clinical value of morphometry performed on cytologic material from benign and malignant pancreatic lesions. METHODS: Cytologic specimens from 100 patients with the diagnosis of pancreatic carcinoma and 15 patients with chronic pancreatitis were evaluated by interactive morphometry using a digital image analyzer system. RESULTS: There were significant differences (p < 0.001) for all morphometric variables between the malignant and benign groups (mean area p 50, 135.41 microns 2 versus 69.66 microns 2; anisokaryosis, 0.74 versus 0.41; and polymorphism, 0.13 versus 0.09). CONCLUSIONS: Morphometry may be used as a complementary tool in the cytologic diagnosis of pancreatic carcinoma.

Adenocarcinoma↗

Adjuvant interferon treatment in human osteosarcoma.

An update of the adjuvant trial on osteosarcoma in Sweden comparing patients receiving natural interferon (IFN) alpha with a high-dose chemotherapy group and a nonadjuvant group is presented. The overall survival for the IFN group is 49%, for the chemotherapy group 54%, and for the nonadjuvant group 35%. Trial evaluation was complicated by group differences with respect to various clinicopathologic features of prognostic significance. The role of IFN in the treatment of osteosarcoma can still not be established.

Bone Neoplasms↗

Morphometric, DNA and PCNA in thin malignant melanomas.

Morphometric assessment of nuclear area, shape and density, nucleolar area, analysis of DNA content and expression of proliferating cell nuclear antigen (PCNA) was performed in a case control study of 72 malignant melanomas, thickness < or = 0.8 mm and Clark level II-III. Twenty-four thin metastasizing melanomas (TMM) were individually compared to two thin non-metastasizing melanomas (TNM) after individual matching for site of primary tumor, tumor thickness, level of invasion, tumor regression and duration of follow-up. Conditional logistic regression analysis with maximum likelihood estimates showed significant differences between TMM and TNM with regard to the nuclear correlation coefficient (p = 0.005), standard deviation of nuclear shape NCI (p = 0.017), and nuclear density (p = 0.030), indicating that thin melanomas with pleomorphic and possibly densely packed nuclei are associated with recurrence. No significant differences were found regarding nuclear or nucleolar area, mean nuclear shape NCI, nuclear DNA content or expression of PCNA.

Antigens, Neoplasm↗

Proliferating cell nuclear antigen (PCNA) expression and nuclear DNA content in predicting recurrence after radiotherapy of early glottic cancer.

Proliferating cell nuclear antigen (PCNA) is a DNA replication protein maximally elevated in late G1 and S phases of the cell cycle. By using monoclonal antibodies, the expression of PCNA can be quantified and the rate of tumour cell proliferation estimated. The degree of DNA aberration in a tumour cell population reflects its genetic instability and has been implicated as a prognostic factor in an increasing number of solid tumours. The nuclear DNA content can be assessed by densitometric image cytometry DNA analysis. Both PCNA and DNA analysis can be performed on histological sections from paraffin embedded biopsies. In search of efficient and reproducible methods to identify early glottic cancers with increased risk for recurrence after radiotherapy, the PCNA expression as well as the DNA content of the diagnostic biopsies from 28 T1N0M0 glottic cancers were assessed. The group of tumours which recurred locally after radiotherapy displayed lower PCNA expression and higher DNA aberration than the group of tumours which were cured. Moreover, a combination of both parameters improved the possibility to discriminate the two groups. For T1 glottic cancer displaying high grade of genetic instability or low grade of proliferation, treatment regimes other than radiotherapy and closer follow-ups could be considered.

Adult↗

Urinary growth hormone excretion in acromegaly: diagnostic value in mild disease activity.

The biochemical assessment of disease activity in acromegaly still presents a problem, especially in treated patients with mild clinical symptoms. We therefore examined the diagnostic value of the measurement of urinary growth hormone (GH) excretion in seventy unselected patients with acromegaly of different activity by comparing it to serum GH, serum insulin-like growth factor I (IGF-I) and clinical activity. There were highly significant, positive correlations between urinary GH and serum GH, serum IGF-I as well as clinical activity score (p < 0.00005), although some overlap between the groups was observed. In seven patients with low serum GH values (< 2.0 micrograms/l) discordant results were found. Two of the seven patients were clinically mildly active, but only IGF-I was either elevated or within the upper normal range; in three other patients who appeared clinically cured either IGF-I (N = 1) or urinary GH (n = 2) alone were increased. In the remaining two patients elevated serum IGF-I and urinary GH as well as activity score suggested disease activity. Thus, in the majority of cases, urinary GH was significantly correlated to the other three parameters, but added little information to that obtained by serum IGF-I. In conclusion, urinary GH measurements in difficult cases may provide a more direct information on the GH status than IGF-I.

Acromegaly↗

Hyponatremia and adrenocortical function in patients with severe bacterial infections.

Hyponatremia occurs frequently in patients with severe infections though its cause has not been established. Recent studies have reported that in some patients with septicemia, adrenocortical insufficiency is present. To ascertain whether occurrence of hyponatremia and adrenocortical insufficiency might be related, we studied 40 patients with septicemia (11 in septic shock). A short corticotropin test was used for assessing the adrenocortical function. Though both adrenocortical failure (in 5 patients) and hyponatremia (serum sodium concentration < 125 mmol/l in 3 patients) occurred, there was no apparent relationship between the entities.

Adrenal Cortex↗

The prognostic value of cytometric DNA analysis in early stage tongue cancer.

In spite of a small size and seemingly localised properties T1 tongue cancer does recur after surgical treatment, locally and/or in regional lymph-nodes, in 30-40% of the patients, and 50% of patients with recurrent disease die because of their cancer. If these patients could be identified by analysis of relevant parameters on the primary biopsy reflecting the biological properties of the tumours more extensive treatment regimes could be given selectively. In 47 primary biopsy specimens from patients with T1N0M0 squamous cell carcinoma of the mobile tongue the aberration in cellular DNA content was significantly higher in the group of tumours which recurred after surgical treatment compared with the non-recurrent group. Tumours in females recurred more frequently than in males. No significant correlation between recurrence and grade of histological differentiation or tumour thickness could be found. Image cytometry DNA analysis provides an objective and reproducible assessment of the nuclear DNA content which could facilitate selection of adequate treatment strategies.

Adult↗

Morphometry and prognosis in cancer of the pancreatic head.

The histological slides of 39 cases of cancer of the pancreatic head were analysed using an interactive image analyser system. Some 14 cases were classified as periampullary, 25 as ductal pancreatic cancer. All cases had undergone radical tumor resection according to Whipple's procedure. Morphometric data, tumor size and metastatic nodal involvement were correlated to prognosis. Univariate statistical analysis showed that the classical differentiation between ductal and periampullary cancer was a weaker prognosticator than morphometric variables. In fact, multivariant statistical analysis showed that the morphometric variable irregularity was the best prognosticator (p = 0.0001). No other variable added significant prognostic information. Irregularity is a newly developed variable describing the nuclear shape corrected for roundness. We conclude that morphometry can be of essential prognostic information for the clinician in cancer of the pancreatic head.

Carcinoma, Intraductal, Noninfiltrating↗