Biomedical subjects
K Lindholm
Publications and source records attributed to K Lindholm.
Ipsilateral local recurrence in relation to therapy and morphological characteristics in patients with ductal carcinoma in situ of the breast.
METHOD AND RESULTS: A standardized histopathological protocol has been designed, in which different histological characteristics of ductal carcinoma in situ (DCIS) are reported: nuclear grade (ng), growth pattern according to Andersen et al., necrosis, size of the lesion, resection margins and focality. Using this protocol a re-evaluation of a population-based consecutive series of 306 cases of DCIS has been done as well as a thorough clinical follow-up. After a median follow-up of 63 months, 13% have developed ipsilateral local recurrences, invasive and/or in situ. Ipsilateral local recurrence-free survival (IL-RFS) was significantly better for patients operated with mastectomy (ME) or breast conserving therapy (BCT) with radiotherapy (RT) than for patients operated with BCT without RT (5-year IL-RFS 96% vs 94% vs 79%, P<0.001). In the subgroup of BCT without RT there were significant differences in IL-RFS between histopathological subgroups: ng 1 + 2 (non-high grade) vs ng 3 (high grade; P=0.014), non-high-grade without comedo-type necrosis vs non-high-grade with comedo-type necrosis vs high-grade (the Van Nuys classification system; P=0.025). Growth pattern (not diffuse vs diffuse) and margins (free vs involved or not evaluated) showed a tendency (P=0.07 and 0.05, respectively) to be associated to IL-RFS. In contrast, no significant differences in IL-RFS were found in subgroups based on mode of detection, focality or size. Ninety-four per cent of the local recurrences after BCT appeared at the previous operation site. CONCLUSIONS: In the BCT without RT group, combinations of either non-high grade and not a diffuse growth pattern or non-high grade and free margins identified groups (constituting approximately 30% of the patients) were at low risk of developing ipsilateral recurrences (6-10%), compared to a 31-37% recurrence risk in the remaining groups during the observed follow-up time. The beneficial effect of post-operative RT for these low-risk groups can be questioned, and should be studied further.
Prediction of invasiveness by aspiration cytology applied to nonpalpable breast carcinoma and tested in 300 cases.
In a retrospective study, fine-needle aspirates from 300 nonpalpable breast carcinomas, including 199 invasive tumors and 101 cases of ductal carcinoma in situ, were analyzed to assess the value of 11 features in predicting invasiveness in malignant breast lesions by aspiration cytology. Four findings appeared to be useful in this context: (1) malignant cell clusters with tubular structure, (2) cytoplasmic lumen formation in malignant cells, (3) fibroblast proliferation, and (4) fragments of elastoid stroma. When any combination of two or more of these key features was seen in a smear being diagnostic of malignancy, the positive predictive value regarding invasiveness was 96%. The accuracy of this prediction in terms of sensitivity and specificity was 48% and 96%, respectively. The clinical use of these observations is discussed.
A DNA cytometric proliferation index improves the value of the DNA ploidy pattern as a prognosticating tool in patients with carcinoma of the prostate.
OBJECTIVES: A still controversial issue is whether the results of a cytometric assessment of the DNA distribution pattern of the nuclei of the neoplastic parenchymal cells of a prostatic adenocarcinoma has additional prognostic value to that of the stage and grade of the disease. To increase the accuracy of the DNA ploidy assessments. Image cytometry (ICM) has been used and combined with the determination of an ICM proliferation index (PI) to increase its value as an additional prognosticating tool. METHODS: We investigated 96 patients, followed up since diagnosis in 1980/1981 until death or, in 11 surviving patients, for an average of 14.5 years. Survival analysis was made by the conventional Kaplan-Meier method. Fine-needle aspiration biopsy was used as the major diagnostic tool. The neoplastic cell nuclei were classified as ICM DNA diploid, tetraploid, or aneuploid by means of the ploidy-establishing peak in the ICM DNA histograms, as well as the fraction of tumor cells in the S-phase. Scattered cells to the right of the ploidy-establishing peak, the S-phase fraction, and those in the G2M area of the ICM DNA histograms were counted as percent of the total number of tumor cells; this percentage was defined as the PI. Arbitrarily, tumors with a PI less than 5% were classified as having a low proliferation rate, those with a PI greater than 10% were considered highly proliferating, and those with a PI between 5% and 10% as carcinomas with an intermediate proliferation potency. RESULTS: By univariate analyses, clinical stage, cytodiagnostic grade, cytometric DNA ploidy pattern and PI all had significant prognostic value. By multivariate analyses, the PI was found to add prognostic information to that of the ICM DNA ploidy pattern variable, giving it an increase in its statistical P value from 0.002 to 0.0005. As a consequence, the combination of these two variables was found to give rise to three new patient groups with regards to their prognosis: DNA group I had tumors with a diploid ICM DNA pattern with a low PI; DNA group II had tumors with a diploid or tetraploid ICM DNA tumor cell nuclei pattern with an intermediate PI; and DNA group III had a diploid or tetraploid ICM DNA pattern with high PI and all tumors with an aneuploid pattern. By multivariate analysis, including tumor grade and clinical stage, these new DNA groups (P = 0.0004) and M stage disease (P = 0.0006) were the only significant prognostic variables. CONCLUSIONS: A DNA cytometric PI improves the prognosticating value of DNA ploidy. Patients with prostatic adenocarcinomas, classified as DNA group I, have a low risk of death from their neoplastic disease with deferred or hormonal treatment only.
Human papilloma virus types in routine cytological screening and at colposcopic examinations.
Certain types of human papillomaviruses (HPV) play a crucial role in the development of anogenital cellular dysplasia and cancer. We have searched for a broad spectrum of HPV-types by PCR in cervical cell samples from 230 women aged 20-29 years enrolled at routine gynecological health control and 506 women referred to colposcopy due to suspected cytological changes. Thirteen percent of the health control women had HPV DNA of identified types. Half of the colposcopy patients showed benign histology with corresponding HPV DNA prevalence of 18%, while among the patients with cervical intraepithelial neoplasia between 61% and 78% had HPV DNA. Among both women with normal cytology or histology and those with various degrees of cervical dysplasia, cancer-related HPV types represented about 85% of the types found. The strong correlation between HPV infections and development of cervical dysplasia is an argument for HPV DNA testing of certain patient groups.
Genital HPV infection not a local but a regional infection: experience from a female teenage group.
OBJECTIVES: To investigate the prevalence of human papillomavirus (HPV) infections in a group of female teenagers, and to analyse to what extent HPV DNA was also detectable, in urethra and cervix samples among the patients with macroscopic genital warts compared with those without. DESIGN: The patients were interviewed about their sexual habits and history of venereal diseases. They underwent a gynaecological health control examination, including macroscopic inspection for genital warts and collection of a cytological vaginal smear (Pap smear). Cell samples were also taken from endocervix and urethra and from vulva lesions, when found. These samples were tested for HPV DNA of the types 6, 11, 16, 18 and 33 using the polymerase chain reaction (PCR) technique. SETTING: An adolescence out-patient clinic in Malmö, Sweden. SUBJECTS: Forty-nine female teenagers consulting for gynaecological complaints, some of them for genital warts. RESULTS: Twenty patients had present and four had a history of genital warts (group A). The other 25 patients had no visible lesions (group B). In the first group (A) 18 of the 24 patients were positive for HPV DNA in one or more of the three locations studied. More patients were positive in urethra (17) than in cervix (15). In group B four of the 25 patients were positive for HPV DNA in urethra, three of these also in cervix. In the two groups 11 and four patients, respectively, showed pathological Pap smears. CONCLUSIONS: The finding of HPV DNA in urethra, both from women with and without visible genital warts, indicates that there is a high probability that the infection is also present in cervix, suggesting that the genital HPV infections are multifocal. Thus, patients with genital warts are most likely to have cervical HPV infections and will more often have pathological Pap smears than patients without warts.
Plexiform fibrohistiocytic tumor. Report of a case involving preoperative aspiration cytology and immunohistochemical and ultrastructural analysis of surgical specimens.
A typical case of plexiform fibrohistiocytic tumor (Enzinger and Zhang) occurring in the skin and subcutis of the abdominal wall in a 7-year-old girl is reported. Preoperative fine-needle aspiration cytology revealed a benign lesion with fibroblastic-histiocytic features which also contained bi- and multinucleated giant cells. The surgical specimen showed a tumor with multiple small nodules within fibrous septa; these nodules were composed of spindle cells and epithelioid cells and contained scattered multinucleated osteoclast-like cells. The tumor cells showed ultrastructural and immunohistochemical features of myofibroblasts and histiocyte-like cells. Thus, there was an abundance of lysosomes, prominent filopodia and bundles of thin cytofilaments along the cytoplasmic border, as well as immunoreactivity for alpha-smooth-muscle-specific actin, alpha-1-antitrypsin and alpha-1-antichymotrypsin. Ultrastructurally there were tumor cells exhibiting features of histiocytes which also contained bundles of actin of smooth muscle type. The presented case of plexiform fibrohistiocytic tumor appears to be composed of a rather peculiar cell form, somewhere between myofibroblasts and histiocytes.
Herpes simplex virus--the most frequently isolated pathogen in the lungs of patients with severe respiratory distress.
308 consecutive patients with severe or complicated respiratory tract infections underwent fiber-optic bronchoscopy in the search for a microbiological etiology. Protected brush specimens were used for bacterial cultures and bronchoalveolar lavage (BAL) for virus isolation and cytological examination. Herpes simplex virus (HSV) was the most commonly found pathogen and was isolated in 37 patients. 20 (54%) of them also had serological and/or cytological signs of HSV infection. 132 patients required assisted ventilation (AV) and in this group 34 (92%) of the 37 HSV positive patients were found. Isolation of HSV was significantly (p less than 0.001) associated with AV compared to patients not requiring AV. Of all patients treated with AV 26% had positive HSV isolation in conjunction with suspected acute lower respiratory infection. Coinfection with HSV and bacteria occurred in only 8 (22%) patients. HSV was more common in patients with burns (47%) compared to other patient groups such as patients with AIDS (3%) or other immunodeficiencies (9%).
Invasive lobular carcinoma: mammographic findings in a 10-year experience.
From January 1, 1976 to December 30, 1985, 1,966 cases of breast carcinoma were diagnosed and treated at Malmo General Hospital, Malmo, Sweden. Of these cases, 185 (9.4%) involved invasive lobular carcinoma (ILC). Mammography in 137 cases demonstrated the following findings: spiculated opacity (53%), architectural distortion (16%), poorly defined opacity (7%), normal or benign findings (16%), and parenchymal asymmetry (4%). Radiographic definition of the ILC lesion varied greatly with projection: The craniocaudal view demonstrated significant findings more frequently than either the oblique or lateral views. Secondary radiographic findings were present in 31%, microcalcifications were rare, and physical findings were present in 89%. Because of its diffuse growth pattern and tendency to form lesions with opacity equal to or less than that of the parenchyma, ILC can be extremely difficult to detect mammographically. Therefore, the radiologist must be alert for subtle mammographic signs of malignancy and highly suspicious of any abnormal physical findings regardless of the mammographic appearance.
Stereotactic, X-ray guided, fine needle aspiration biopsy of nonpalpable breast lesions: comparison with the coordinate grid localization technique.
Explore the source record for details and available documents.
Stereotactic fine-needle aspiration for cytologic diagnosis of nonpalpable breast lesions.
Fine-needle aspiration for cytologic diagnosis was performed on 219 nonpalpable breast lesions by using a stereotactic localization technique. Cytologic results were correlated with mammographic findings, and therapeutic decisions were based on the results of both procedures. Representative cytologic material was obtained in 74% of the lesions. Strict criteria of representativeness were observed. If only cases with representative cytologic yield are considered, the sensitivity was 93% and the specificity was 97%. The predictive values were high except for the predictive value of a negative cytologic finding in a spiculated lesion (50%). Sampling errors caused by abundant fibrosis, needle deviation, and difficulty in defining the lesion on the stereoscopic views are discussed. Another source of sampling error may be the mixed nature of some lesions consisting of benign and malignant components. Fine-needle aspiration of 219 nonpalpable breast lesions by using a stereotactic localization device yielded representative cytologic samples in 74% of the lesions.
Intravesical mitomycin C for carcinoma in situ of the urinary bladder.
Mitomycin C was given intravesically over periods of 2-32 months to 34 patients with carcinoma in situ of the urinary bladder. Initial complete response was obtained in 17 patients, 14 of whom remained without evidence of disease during follow-up averaging 28 months from cessation of mitomycin therapy. In three responding patients malignant cells reappeared in the urine during follow-up, although no recurrence of carcinoma could be proven in bladder biopsy specimens. In eight of the 17 non-responders, muscle invasion and/or metastatic disease developed during or after mitomycin treatment. The prostatic urethra was involved in five cases. Chemotherapy had to be discontinued because of chemical cystitis in three cases. Mitomycin C appears to be effective for intravesical treatment of carcinoma in situ of the urinary bladder. Close surveillance of these patients is mandatory, however, and must include monitoring not only of the bladder, but also of the prostatic urethra and the upper urinary tract.
Flow DNA analysis in the characterization of carcinoma of the renal pelvis and ureter.
A prospective study comprised operative specimens from 11 patients with transitional cell carcinoma of the renal pelvis or ureter. DNA analysis of the primary tumor and of multiple biopsy specimens from preselected sites of the surrounding urothelium was performed with flow cytometry. All Grade 3 tumors and 50% of the Grade 2 tumors were aneuploid, and the remainder were Grade 2 and diploid. All invasive tumors were aneuploid. Carcinoma in situ was found in some of the preselected biopsy specimens, all of which were aneuploid, from two patients. Close correlation thus was observed between aneuploidy and tumor invasiveness, whereas diploidy was seen only in noninvasive tumors with lower malignancy grade. Aneuploidy was also associated with increased risk of carcinoma in situ. The study indicated that DNA analysis may be useful for defining the malignant potential of urothelial tumors of the upper urinary tract more fully than conventional grading and staging permit.
Radical radiotherapy in prostatic carcinoma.
During the years 1978-1986 111 fairly elderly patients with prostatic carcinoma in clinical stages B, C, or D, and usually having tumours that were poorly differentiated, received radical radiotherapy to the prostate and bladder and to the adjacent lymph node regions. The side effects were comparable to those reported in the literature. During the follow-up 72% of the patients sooner or later (actuarial analysis) developed local recurrence or distant metastases. The projected survival rate at 8 years was 25%, and should be compared with the 65% expected for an age-matched Swedish male population. After 3 years the two survival curves became rather parallel, indicating a 'cure' rate of the order of 49%. There was a significant difference in survival between patients clinically judged to have only intracapsular carcinoma and those considered to have extracapsular carcinoma. The relatively modest survival figures in the present series reflect the malignant nature of poorly differentiated carcinoma of the prostate.
Mammographic screening and mortality from breast cancer: the Malmö mammographic screening trial.
STUDY OBJECTIVE: To determine whether mortality from breast cancer could be reduced by repeated mammographic screening. DESIGN: Birth year cohorts of city population separately randomised into study and control groups. SETTING: Screening clinic outside main hospital. PATIENTS: Women aged over 45; 21,088 invited for screening and 21,195 in control group. INTERVENTIONS: Women in the study group were invited to attend for mammographic screening at intervals of 18-24 months. Five rounds of screening were completed. Breast cancer was treated according to stage at diagnosis. END POINT: Mortality from breast cancer. MEASUREMENTS AND MAIN RESULTS: All women were followed up and classed at end point as alive without breast cancer, alive with breast cancer, dead from breast cancer, or dead from other causes. Cause of death was taken from national mortality registry and for patients with breast cancer was validated independently. Mean follow up was 8.8 years. Altogether 588 cases of breast cancer were diagnosed in the study group and 447 in the control group; 99 v 94 women died of all causes and 63 v 66 women died of breast cancer (no significant difference; relative risk 0.96 (95% confidence interval 0.68 to 1.35)). In the study group 29% more women aged less than 55 died of breast cancer (28 v 22; relative risk 1.29 (0.74 to 2.25)). More women in the study group died from breast cancer in the first seven years; after that the trend reversed, especially in women aged greater than or equal to 55 at entry. Overall, women in the study group aged greater than or equal to 55 had a 20% reduction in mortality from breast cancer (35 v 44; relative risk 0.79 (0.51 to 1.24)). OTHER FINDINGS: In the study group 100 (17%) cancers appeared in intervals between screenings and 107 (18%) in non-attenders; 51 of these women died from breast cancer. Cancers classed as stages II-IV comprised 33% (190/579) of cancers in the study group and 52% (231/443) in the control group. CONCLUSIONS: Invitation to mammographic screening may lead to reduced mortality from breast cancer, at least in women aged 55 or over.
X-ray guided fine-needle aspiration for the cytologic diagnosis of nonpalpable breast lesions.
X-ray guided localization of 215 nonpalpable, mammographically detected, breast lesions for fine-needle aspiration biopsy was performed using a two-dimensional coordinate grid. Representative material was obtained in 64% of the lesions. Very strict criteria of representativity were observed. The sensitivity of the cytologic procedure was 92%, the specificity 95%, the predictive value of positive cytologic diagnosis 88%, and the predictive value of a negative cytologic diagnosis 97%. Potential pitfalls in the localization and aspiration procedures are discussed. The results of cytologic examination should always be correlated with the mammographic findings, and further diagnostic and therapeutic decisions should be based on both modalities. In this setting, x-ray guided fine-needle aspiration cytologic study is a highly valuable diagnostic tool.
Needle-tract seeding after percutaneous fine-needle biopsy of pancreatic carcinoma. Case report.
Needle-tract seeding is a rare complication following percutaneous fine-needle biopsy of intra-abdominal tumours and only a few cases have been reported. Two cases of cutaneous implantation of a tumour in the needle-tract after biopsy of pancreatic carcinomas are presented. In experimental studies, seeding of malignant cells in the needle-tracts is common and the discrepancy between experimental and clinical findings is discussed.
Salivary immunoglobulin concentrations in predentate and edentulous mouths.
The concentrations of IgA, IgG and IgM in whole saliva of predentate babies, dentate adults, and edentulous old people, and the salivary IgG concentration of dentate old people, were determined using a solid phase radioimmunoassay. A highly significant difference in IgG concentrations was found between toothless and dentate people. The average IgG concentration in the saliva of edentulous old people was 5.2 mg/1, which was about 20% of that of dentate old people. The salivary IgG content of babies was only 1.7 mg/1, which was in concordance with the low postnatal serum IgG values. The salivary IgA level in this age group was also low. The edentulous old people tended to have decreased IgM values, and the predentate babies tended to have increased IgM values compared with the dentate adults.