Biomedical subjects

A Ringberg

Publications and source records attributed to A Ringberg.

At least 19 recordsLinked to original sources

PubMed2006

Histopathological risk factors for ipsilateral breast events after breast conserving treatment for ductal carcinoma in situ of the breast--results from the Swedish randomised trial.

AIM: The primary aims were to study risk factors for an ipsilateral breast event (IBE) after sector resection for ductal carcinoma in situ of the breast (DCIS) in a trial comparing adjuvant radiotherapy to no therapy and to assess predictive factors for response to radiotherapy. Secondary aims were to analyse reproducibility of the histopathological evaluation and to estimate correctness of diagnosis in the trial. SETTING: A randomised trial in Sweden (the SweDCIS trial), including 1046 women with a median of 5.2 years of follow-up in a population, offered routine mammographic screening. METHODS: A case-cohort design with a total of 161 cases of IBE (42 of those being members of the subcohort) and 284 sampled for the sub-cohort. Ninety five percent of the participants' slides could be retrieved and were re-evaluated by three experienced pathologists. RESULTS: Low nuclear grade (NG 1-2) and absence of necrosis halves the risk of IBE in both irradiated and non-irradiated patients. Lesion size, margins of excision and age at diagnosis did not modify these associations. The presence of necrosis modified the effect of radiotherapy: relative risk was 0.40 with necrosis present and 0.07 with necrosis absent (p-value for interaction 0.068). In all subsets of prognostic factors, radiotherapy conferred a substantial benefit. The risk factors for in situ and invasive IBE were similar. The agreement between pathologists was moderate (kappa=0.486). Correctness of diagnosis in the subcohort of SweDCIS was 84.8%. CONCLUSION: Although nuclear grade and necrosis carry prognostic information, we could not define a group with very low risk after sector resection alone. Radiotherapy has a protective effect in all substrata of risk factors studied. The interaction between the presence of necrosis and radiotherapy is a clinically and biologically relevant research area.

Breast Neoplasms↗

PubMed2003

Tissue microarray analyses of G1/S-regulatory proteins in ductal carcinoma in situ of the breast indicate that low cyclin D1 is associated with local recurrence.

Ductal carcinoma in situ (DCIS) of the breast constitutes about 10% of all diagnosed breast cancers and, despite surgical removal, it may recur, either as DCIS or invasive breast cancer. Nuclear grade and growth pattern according to Andersen et al as well as surgical margins are factors that have been used to predict local recurrence, but ideally a set of tumour-specific factors should be identified and used as prognostic markers. Many cell cycle regulatory gene products have been shown to be involved in the formation of tumours and are either oncogenes or suppressor genes and involved in key processes in the transformation. We therefore characterised the cell cycle regulators cyclin E, cyclin D1, p27 and p16 in a material of DCIS cases arranged in a tissue microarray. With a manual tissue arrayer, 52% of the initial 177 DCIS samples were successfully targeted allowing immunohistochemical analyses of all four proteins in 92 cases of DCIS. As also observed in invasive breast cancer, there was a trend indicating that DCIS cases with high cyclin D1 were cyclin E low and oestrogen receptor-positive, whereas cyclin E high DCIS cases were cyclin D1 low and oestrogen receptor-negative. For the 64 patients that did not receive postoperative radiotherapy, there were 16 local recurrences (eight DCIS and eight invasive breast cancer) during a mean follow-up time of 63 months. Cyclin E, p27 or p16 were not associated with local recurrence, but interestingly cyclin D1 was significantly and inversely associated with local recurrence, both using univariate and multivariate analyses. In summary, using a tissue array approach we have shown that cyclin D1, besides growth pattern, is a prognostic marker for local recurrence in DCIS.

Biomarkers, Tumor↗

PubMed2003

Are cellular polarisation and mitotic frequency prognostic factors for local recurrence in patients with ductal carcinoma in situ of the breast?

There is still no generally accepted histopathological classification system for ductal carcinoma in situ (DCIS) of the breast. Nuclear grade, with or without other histopathological parameters (i.e. comedo-type necrosis and cellular polarisation), has been demonstrated to yield prognostic information. A detailed method for the evaluation of the mitotic frequency in DCIS, based on an approach by Contesso, was used in this study. We also investigated if cellular polarisation and mitotic frequency were important for the ipsilateral local recurrence-free interval (IL-RFI) in 121 DCIS patients who had been operated upon with breast-conserving treatment (BCT) without radiotherapy. Both cellular polarisation and the mitotic frequency were associated with histopathological and cellular biological factors (in previous evaluations), and were of borderline significance for IL-RFI in the univariate analyses. However, when nuclear grade was included in the multivariate analyses (with or without the growth pattern), neither cellular polarisation nor the mitotic frequency were of any independent prognostic value.

Adult↗

PubMed2001

Cell biological factors in ductal carcinoma in situ (DCIS) of the breast-relationship to ipsilateral local recurrence and histopathological characteristics.

All cases of ductal carcinoma in situ (DCIS) diagnosed from 1987 to 1991 in the Southern Health Care Region of Sweden, and operated upon with breast conserving treatment (BCT) with (n=66) or without (n=121) postoperative radiation (RT) were clinically followed, morphologically re-evaluated and analysed for cell biological factors (immunohistochemical assays or DNA flow cytometry). Median age at diagnosis was 58 years (range 29--83 years) and median follow-up was 62 months. Oestrogen (ER)- and progesterone receptor (PR)-negativity, c-erbB-2 overexpression, low bcl-2 expression, p53 accumulation, DNA non-diploidy and high Ki67, were strongly associated with high grade DCIS, and comedo-type necrosis. In contrast, significant associations to growth pattern (not diffuse versus diffuse) were seen only for c-erbB-2 and PgR. There was also a strong relationship between the cell biological factors, and a summary cell biological index based on principal component analysis was introduced (CBI-7). In the group that had not received postoperative RT, 31 ipsilateral local recurrences occurred (13 invasive, 18 DCIS). Ipsilateral recurrence-free interval (IL-RFI) was in univariate analyses significantly, or almost significantly, shorter for patients showing p53 accumulation, high Ki67 or low bcl-2, compared with patients with normal p53, low Ki67 and high bcl-2. The prognostic importance of the remaining cell biological factors was less pronounced. On the other hand, the index CBI-7, was a strong predictor for recurrence.

Adult↗

PubMed2001

Histopathological and cell biological factors of ductal carcinoma in situ before and after the introduction of mammographic screening.

With the introduction of mammographic screening the incidence of ductal carcinoma in situ (DCIS) has increased to 10-15% of all breast cancers. The aim of this study was to investigate whether there were any morphological and cell biological differences between DCIS detected during the pre-screening (n = 39) as opposed to the screening period (n = 120). We could not demonstrate any statistically significant differences between the pre-screening and the screening period with regard to nuclear grade, presence of necrosis, the Van Nuys classification system, growth pattern, or cell biological factors (estrogen and progesterone receptors, c-erbB-2, p53, DNA ploidy status, Ki67, and Auer classes). These findings suggest that DCIS tumors detected during the two time periods have a similar malignant potential. DCIS detected during the screening period was further divided into the prevalence period versus the period thereafter, and symptomatic versus screening-detected asymptomatic cases. More cases with diffuse growth patterns were seen during the prevalence period than after the prevalence period, and screening-detected asymptomatic DCISs were more often 15 mm or smaller in diameter than DCISs detected symptomatically.

Biomarkers, Tumor↗

PubMed2001

Self-reported symptoms among women after cosmetic breast implant and breast reduction surgery.

A retrospective cohort study was performed in Sweden to evaluate the possibility that an individual symptom or constellation of illness symptoms related to silicone occurs in women after breast implant surgery. A random sample (n = 2500) of all women in the Swedish national implant registry who underwent breast augmentation surgery with alloplastic breast implants during the years 1965 through 1993 was compared with a sample (n = 3500) of women who underwent breast reduction surgery during the same period, frequency matched to the implant patients for age and calendar year at the time of surgery. In total, 65 percent of the breast implant patients (n = 1546) and 72 percent of the breast reduction patients (n = 2496) completed a self-administered questionnaire covering 28 rheumatologic and other symptoms and lifestyle and demographic factors. Practically all of the 28 symptoms inquired about were reported more often by women in the breast implant cohort, with 16 (57 percent) significantly more common in breast implant recipients. In contrast, few significant differences or consistent patterns were observed in the length of time since the implant and in the type (silicone or saline) or volume of the implant. Although women with breast implants report a multitude of symptoms more often than women who have breast reduction surgery, the lack of specificity and absence of dose-response relationships suggest that the excess of reported symptoms is not causally related to cosmetic implants.

Adult↗

PubMed2000

Accrual rate-limiting factors in a Swedish randomised ductal carcinoma in situ (DCIS) trial - a demographic study.

In the last two decades the introduction of mammographic screening in the Western world has increased the number of diagnosed ductal carcinomas in situ (DCIS) considerably. In situ carcinoma of the breast is considered a heterogeneous disease, the natural history of which is not well known. Thus, appropriate treatment needs to be established. For this reason, a randomised trial studying the effect of breast conserving operation with or without postoperative radiotherapy was instituted in Southern Sweden in 1987. The aim of the present study was to assess patient accrual, identify limiting factors, and evaluate possible ways to influence these factors in order to increase patient accrual. Between 1987 and 1992, 331 patients had been registered with DCIS in the Regional Tumour Registry, 96 of which had been randomised. All 331 were subjected to chart review studying clinical data, mammography reports, cytology and pathology reports to identify inclusion and exclusion criteria according to the design of the trial. It was found that 5% (18/331) had an incorrect diagnosis of DCIS. According to the trial protocol 52% were not eligible (162/313). Fifty-eight per cent (n=88) of the 151 eligible patients had been correctly randomised. The most common reason for exclusion was lesion size. In 21% (66/313) the lesion was 'too large'. Several other limiting factors were identified such as in cytological and pathological definitions and reports, lack of information/awareness in certain physicians, patient reluctance to participate, which in turn may be influenced by the previous factor. With increased information to participating hospitals and considering the above given facts it should be possible to increase accrual from the 28% noted in the present consecutive demographic study to at least one-third of the diagnosed cases of DCIS.

Breast Neoplasms↗

PubMed2000

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.

Adult↗

PubMed2000

Histologic grading in breast cancer--reproducibility between seven pathologic departments. South Sweden Breast Cancer Group.

Histologic grade, including tubular formations, nuclear grade, and mitotic activity, is a well-documented prognostic factor in breast cancer. In comparison with other prognostic parameters, the evaluation of histologic grade is cheap and can be performed, in principle, in all cases of breast cancer. One possible disadvantage is that the evaluation may vary between different pathological departments. The aim of the present work was therefore to study the reproducibility of the histologic grading system by distributing haematoxylin-erythrosin-stained slides from 93 invasive breast cancers to the seven pathology departments within the southern healthcare region of Sweden. The evaluation was performed blindly and without any knowledge of other clinical parameters. In 31% of the cases the same histologic grade was obtained for all departments. The overall mean kappa was 0.54, indicating a moderate reproducibility. Of the three factors included in histologic grade, the agreement was best for tubular formations and poorest for nuclear grade and mitotic activity. The overall moderate reproducibility should be considered when the clinical usefulness of histologic grading is compared with other prognostic instruments.

Adult↗

PubMed1999

Immediate breast reconstruction after mastectomy for cancer.

AIMS: The oncological, surgical and cosmetic results, patient satisfaction and psychological morbidity of immediate breast reconstruction following mastectomy for breast cancer were evaluated. METHODS: From 1980 to 1994, 79 immediate breast reconstructions were performed in Malmö. From 1985 immediate breast reconstruction was performed in 21% of mastectomies among patients </=65 years. The most common indication for immediate reconstruction was extensive DCIS+/-multifocal invasive growth. In 61 cases permanent implants were used and in 18 expanders. The median volume in the permanent implants was 225 ml, compared with 380 ml in cases where expanders were used. RESULTS: Post-operative complications requiring re-operation occurred in 13%. After introduction of the expander technique, no necrosis requiring explanation has occurred. Of the patients receiving radiotherapy, 71% developed capsular contracture (10/14). Four patients developed locoregional recurrence. Three-quarters of the patients had an acceptable to very satisfactory cosmetic result. Eight per cent were judged to have a Baker III-IV contracture. Of the patients, 85% were satisfied with the softness of the reconstructed breast and 76% stated the result to be in accordance with their expectations. CONCLUSIONS: We find immediate breast reconstruction after mastectomy a safe operation with results comparable to those after late reconstruction and without an increased risk of recurrence. Immediate reconstruction with an implant is not recommended in cases where radiotherapy may be necessary.

Adult↗

PubMed1996

Chromosome aberrations in prophylactic mastectomies from women belonging to breast cancer families.

Short-term cultures of samples from eight prophylactic mastectomies from five unrelated women who were genetically predisposed to breast cancer were analyzed cytogenetically. Clonal chromosome abnormalities were detected in five breasts. Three samples from two women had aberrations involving the short arm of chromosome 3, with a breakpoint in 3p14 in common. Three samples from three women had rearrangements of 1q. Two of them, one of which also displayed a 3p14 rearrangement, shared a breakpoint in 1q41. Both 1q41 and, in particular, 3p14 have been reported to be rearranged frequently in malignant breast proliferations. Whether alterations of genes in these bands are essential in mammary tumorigenesis and, if so, whether they are equally important in sporadic and in hereditary cases remains to be explored.

Adult↗

PubMed1991

Breast carcinoma in situ in 167 women--incidence, mode of presentation, therapy and follow-up.

In the city of Malmö, in southern Sweden, 1693 women were diagnosed as having breast carcinoma during 1976 through 1984. Of these, 167 women had pure in situ breast carcinoma (9.9%). One hundred and thirty-two had ductal carcinoma in situ (DCIS) alone or in combination with lobular carcinoma in situ (LCIS), intracystic carcinoma and/or Paget's disease of the nipple. Thirty-three had pure LCIS and two had pure intracystic carcinomas. The incidence of breast carcinoma in situ (CIS) in women 20 years of age or older was 18.7 per 10(5) woman years with high rates of DCIS for all ages above 40, whereas a decline in incidence rate was seen for LCIS in the postmenopausal age groups. The ratio of DCIS to LCIS was 4:1. Of the 132 patients with DCIS, 46% were asymptomatic and were diagnosed by mammography, 35% presented with clinical symptoms, and 19% of the cases were incidental findings in breasts operated on for benign lesions. Mammography had been performed on all patients with DCIS and contributed to diagnosis in 75%. Sixty-one per cent of all DCIS lesions had microcalcifications suspicious for carcinoma. Eighty-nine of 132 patients with DCIS underwent fine-needle aspiration biopsy (FNAB) before surgical biopsy. FNAB was suspicious or diagnostic for carcinoma in 57/89 (64%). Of 33 cases with LCIS all but one were incidental findings. In one of 28 cases with LCIS examined by mammography there was suspicion of carcinoma. Sixteen per cent of the patients with DCIS were treated by a breast-conserving operation (BCO), the remaining patients by mastectomy (ME) (52%) or subcutaneous mastectomy (SCM) (33%) with immediate reconstruction. Thirty-three per cent of the patients with LCIS were treated by BCO, the remaining patients by ME (18%) or SCM (49%) with immediate reconstruction. Only one patient had radiotherapy postoperatively. In 60% of all CIS cases where an excisional biopsy had been performed there were further foci of CIS in the final ME/SCM specimen. After a median follow-up of 7 years for the DCIS group, three patients out of 21 treated by BCO had invasive carcinoma appearing ipsilaterally. They were alive and without symptoms of recurrent disease 2.5 to 6 years following further surgery. One patient treated by SCM died from generalized ductal breast carcinoma. In the LCIS group (median follow-up 8 years) one patient out of 11 had an invasive tubular carcinoma diagnosed 4 years after BCO. Eight years later she was alive and well after bilateral SCM.

Adult↗

PubMed1991

Bilateral and multifocal breast carcinoma. A clinical and autopsy study with special emphasis on carcinoma in situ.

Bilateral clinical breast carcinoma has been reported to appear in up to approximately 10% of patients with breast carcinoma. Increasing diagnostic activity has raised figures of bilaterality, mainly due to detection of lesions of the in situ type. Knowledge of the natural history of carcinoma in situ is incomplete and clinical implications are uncertain. In the present study bilateral lesions were analysed by extensive histological examination in the following groups of patients: (1) Forty-six women (median age 44 years) with clinical and mammographical unilateral invasive breast carcinoma, where the contralateral breast was removed at subcutaneous mastectomy (SCM) during the course of breast reconstruction, 24/46 (52%) had bilateral malignant lesions, four invasive carcinomas and 20 in situ carcinomas (two ductal carcinomas in situ /DCIS/, 15 lobular carcinomas in situ (LCIS), three both DCIS and LCIS). (2) Fifty-two women (median age 50 years) with a unilateral diagnosis of in situ carcinoma (32 DCIS, 16 LCIS, four both DCIS and LCIS), in whom both breasts were removed at SCM. 25/52 (48%) had bilateral malignant lesions, one invasive carcinoma, 24 in situ carcinomas (three DCIS, 18 LCIS, three both DCIS and LCIS). Twelve of 20 cases with LCIS (60%) were bilateral. Of 36 cases with DCIS, seven (19%) were bilateral. (3) The contralateral breast was removed at autopsy in 64 women previously unilaterally mastectomized (at median age 65) for invasive breast carcinoma. Fifteen of 64 (23%) had contralateral primary carcinoma at autopsy, four invasive carcinomas, 11 in situ carcinomas (six DCIS, five LCIS) and 8/64 (13%) had metastases in the breast. Multifocal malignant findings were also analysed in 47 SCM specimens after excisional biopsy for in situ carcinoma. In 35/47 (75%) further malignant lesions were present in spite of normal mammographic and clinical findings. Four were invasive and 31 had in situ lesions (16 DCIS, 10 LCIS, five both DCIS and LCIS): These findings may favour the hypothesis that some carcinomas in situ may remain silent or even regress. It is thus important to embark upon randomized trials to clarify the natural history of breast carcinoma in situ. Such a trial has been started in the southern region of Sweden.

Adenocarcinoma↗

PubMed1990

Mandibular-facial reconstruction with segmentally split serratus anterior composite flaps.

Oncologic or traumatic head and neck defects with missing mandible, facial skin, and oral mucosa are especially well suited to reconstruction with a composite tissue unit, based on the subscapular-thoracodorsal vessels, that carries any combination of skin, bone, and muscle to restore vascularized skeletal structures, oral lining, and skin cover. The subscapular-thoracodorsal vascular pedicles supply segmentally split units of the lower serratus muscle and ribs on which it originates. Also, one or two skin paddles for cover and lining flaps are carried either by the cutaneous scapular and parascapular branches of the circumflex scapular vessels or by surgically split segments of the latissimus dorsi musculocutaneous flap. The composite flap can be designed in a variety of combinations to meet recipient defect needs and allow retained innervated segments of the component muscles in situ for preservation of donor motor function. The common subscapular-thoracodorsal vascular pedicle can be transferred either as a microvascular free flap or by pedicle transposition through a subpectoral-subplatysmal tunnel to the mandibular-facial defect. This versatile reconstructive unit illustrates many of the refinements of contemporary flap reconstructions.

Face↗

PubMed1987

Thermography after subcutaneous mastectomy and reconstruction with silicone gel prosthesis: a pilot study.

Patients with subcutaneously placed silicone gel prostheses, for reconstruction after subcutaneous mastectomies, often complain of cold breasts as well as of slow regaining of warmth after cooling. We have used thermography in 7 such women and in 7 healthy women of the same age group as controls. Thermography has also been used in 3 women after repositioning of the subcutaneously placed prostheses to a submuscular position in order to study any possible changes in temperature. In 2 cases thermography also was found to aid in the diagnosis of a suspected subcutaneous displacement of a submuscular prosthesis; the technique has an advantage over mammographic examination, since thermography is a simple, less expensive, and safer method.

Bioprosthesis↗

PubMed1987

Augmentation mammaplasty--psychiatric and psychosocial characteristics and outcome in a group of Swedish women.

Thirty-eight women undergoing augmentation mammaplasty, consecutively operated on at the Department of Plastic and Reconstructive Surgery, Malmö, Sweden, were studied preoperatively regarding medical history, personality, psychosocial and psychiatric characteristics. Thirty-six of these patients were interviewed one year postoperatively. Thirty-three age-matched women operated on with minor surgical out-patient procedures were used as a contrast group. The mammaplasty patients generally came from insecure homes with conflicts between parents and unsatisfactory emotional relations to both parents. Their educational as well as income level was significantly lower than the contrast group and they were socially isolated. Their sexual adaptation seemed to have been hampered by their sensitivity reactions towards their breasts but nonetheless most of them lived in stable heterosexual relations. Generally the augmentation mammaplasty patients were not psychiatrically abnormal apart from the negative evaluation of their physical attractiveness. The great majority of the women, 86%, were satisfied with the results of surgery. Postoperatively the patients changed their style of dressing, extended their leisure time activities and social contacts, improved their sexual life and relations to their spouse. Postoperative increase of nervous symptoms was reported by 39% of the patients, but about as many patients, 36%, reported decreased nervous symptoms. Difficulties in accepting the surgical result, sexual dysfunctions and negative mental reactions proved to be associated with specific personality characteristics. Various factors have previously been proposed as being usable in the prediction of adverse reactions after augmentation mammaplasty. None of these factors, however, proved in this study to correlate with postoperative maladaptation. A need for increased methodological stringency in predictor studies is indicated.

Adaptation, Psychological↗

PubMed1986

A prospective study of psychiatric and psychosocial sequelae of bilateral subcutaneous mastectomy.

Short- and long-term adaptation (two months and one year respectively) to bilateral subcutaneous mastectomy was studied in twenty-five consecutive patients operated upon at the Department of Plastic and Reconstructive Surgery, Malmö, Sweden. The results were related to preoperative personality and psychosocial profiles. Postoperative difficulties in accepting the surgical result, sexual dysfunctions and mental reactions with depression and anxiety were observed. Such reactions proved to be associated with specific personality characteristics.

Adaptation, Psychological↗

PubMed1985

Breast reductions: what to do with all the tissue specimens?

In order to find some guidelines for adequate examination of the often very large amount of tissue removed at reduction mammoplasties, a thorough macro- and microscopic study of a total of 400 specimens from 200 consecutive cases of bilateral breast reductions was done. The majority of patients were younger than 30 years of age. In these cases no abnormalities were found and a thorough macroscopic examination performed by an experienced pathologist is believed to be sufficient in this age group. In older women we encountered diverse findings, the most noteworthy being lobular carcinoma in situ in 8% of patients in this series who were over 40 years of age. This indicates the need for generous histological sampling in this age group. The potential value of roentgenological examination is also discussed.

Adolescent↗