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Biomedical subjects

K Sandelin

Publications and source records attributed to K Sandelin.

At least 19 recordsLinked to original sources

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↗

Expression of Syndecan-1 in histologically normal breast tissue from postmenopausal women with breast cancer according to mammographic density.

OBJECTIVE: To analyze the expression of Syndecan-1 in dense and non-dense human breast tissue. METHODS: Specimens of histologically normal tissue were obtained from postmenopausal women undergoing surgery for breast cancer. Each tissue block was subject to radiological examination and pair-wise samples of dense and non-dense tissue were collected. Semi-quantitative assessment of immunohistochemical staining intensity for Syndecan-1 and estrogen receptor subtypes was performed. RESULTS: The expression of Syndecan-1 in all tissue compartments was significantly higher in dense than in non-dense specimens. The strongest staining was recorded in stromal tissue. There was a strong correlation between epithelial estrogen receptor alpha and stromal cell Syndecan-1 expression in dense tissue (rs = 0.7; p = 0.02). This association was absent in non-dense tissue. CONCLUSION: An increase of Syndecan-1 in all tissue compartments and a redistribution from epithelium to stroma may be a characteristic feature for dense breast tissue.

Breast↗

Analgesic efficacy of diclofenac in combination with morphine and paracetamol after mastectomy and immediate breast reconstruction.

BACKGROUND: Breast cancer treatment with mastectomy and immediate breast reconstruction (IBR) is associated with intense pain in the primary post-operative period. The present prospective, placebo-controlled and double-blind study aimed to evaluate the analgesic efficacy of diclofenac, a non-steroid anti-inflammatory drug (NSAID), in combination with paracetamol and opioids. This was done by 64-h assessment of post-operative pain intensity, opioid consumption, blood loss, nausea and tiredness. METHODS: Fifty women selected for mastectomy and IBR with submuscular implants with or without axillary lymph node dissection (ALND) were randomized to receive diclofenac 50 mg x 3 or placebo rectally in addition to oral paracetamol and intravenous opioids delivered using a patient-controlled analgesia (PCA) technique. RESULTS: During the first 20 h post-surgery, patients who received diclofenac experienced significantly less pain when resting than those who received placebo. When moving, a non-significant estimated difference in pain in favour of diclofenac was also noted. Opioid consumption during the first 6 h post-operatively was 34% less with diclofenac than with placebo. Means (SD) were 16.9 (10.3) mg and 25.6 (10.2) mg, respectively (P = 0.007). After 64 h, the difference was no longer statistically significant. Post-operative bleeding was significantly higher with diclofenac than with placebo (P < 0.01). Nausea and tiredness did not differ between the groups. CONCLUSIONS: The addition of NSAID to paracetamol and opioid-PCA reduced opioid consumption and improved pain relief during the first 20 h at rest but was not convincingly effective during mobilization. Post-operative blood loss was higher with diclofenac.

Acetaminophen↗

Oncological outcome after immediate breast reconstruction for invasive breast cancer: a long-term study.

Immediate breast reconstruction (IBR) was implemented in 1990. Patients operated on for invasive breast cancer were assessed for oncological outcome after a minimum of 5-year follow-up. The study had a form of a retrospective analysis of 203 consecutive patients. The indications for IBR were always discussed in multidisciplinary case conferences. The pectoralis major fascia was left in place. The implant technique dominated. The break down by tumor stage was T1 tumors in 122 cases, T2 in 72, and T3 tumors in nine. Preoperative chemotherapy was given to 21 patients for tumors > 4 cm. Thirteen patients, or 6.5%, developed a local recurrence and seven are still alive with their reconstructed breast after excisions, chemo- and radiation therapy. Most (11) of the 13 recurrences occurred within 24 months after IBR. The recurrence rate remained low with this surgery plus reconstruction approach and IBR is therefore considered a safe procedure when implemented by a multidisciplinary team. Most recurrences appear within 2 years after reconstruction.

Adult↗

Preoperative psychological reactions and quality of life among women with an increased risk of breast cancer who are considering a prophylactic mastectomy.

A consecutive sample of 56 women with a familial risk for breast cancer who were considering a prophylactic mastectomy (PM) completed questionnaires preoperatively concerning risk perception, expectations with regard to surgery, anxiety and depressive symptoms (the Hospital Anxiety and Depression Scale (HAD) scale) and quality of life (The Swedish SF-36 Health Survey). 16 had had a previous breast cancer (Group BC) and 40 had not (Group R). They were compared with normative data from an age-matched random sample of the Swedish population and with a reference sample of women with breast cancer. Most women estimated their breast cancer risk accurately. No statistically significant differences were found between Group BC and the normative sample on the HAD scale and SF-36, but Group R reported better physical functioning, emotional role functioning and mental health than the reference sample with breast cancer. Group BC scored closer to them than to the normative sample. Levels of emotional problems and quality of life were comparable to normative values among women considering PM. All women in the present study had previous genetic counselling and our results suggest that their interest in PM was not due to an overestimation of their personal risk.

Adult↗

A randomised study of axillary drainage and pectoral fascia preservation after mastectomy for breast cancer.

BACKGROUND: To reduce the risk of seroma after modified radical mastectomy in breast cancer patients, the use of suction axillary drainage is a standard procedure. The optimal time to remove the drain is not established. Whether the removal or preservation of the pectoral fascia influences the risk of seroma formation or loco-regional recurrence rate remains unclear. METHOD: The trial included 247 patients with breast cancer who underwent modified radical mastectomy in five Swedish hospitals 1993-1997. The median follow-up time was 6 years. One hundred and twenty-two and 125 patients, respectively, were randomised between removal versus preservation of the pectoral fascia. Of these 247 patients a total of 198 patients were also randomised to have the drain removed 24 h postoperatively or to keep the drain in until discharge had decreased to less than 40 ml/24 h. RESULTS: Early removal of the axillary drain was associated with significantly more seromas and a shorter average postoperative hospital stay. There were no differences between the two groups regarding the rate of wound infections and/or hematoma formation. Removal or preservation of the pectoral fascia did not influence the formation of seroma or the amount of peroperative bleeding. A trend towards an increased risk for chest wall recurrence was observed in patients with preserved pectoral fascia (16/125 compared with 8/122; hazard ratio=2.0, 95% confidence interval=0.9-4.7). CONCLUSION: Early removal of axillary drain shortened the duration of hospital stay without any increase in wound complications. However, it yielded a significantly higher incidence of seroma. Seroma formation and the chest wall recurrence rate was not significantly influenced by the preservation of the pectoral fascia or not.

Aged↗

Immediate reconstruction in breast cancer surgery requires intensive post-operative pain treatment but the effects of axillary dissection may be more predictive of chronic pain.

The aim of this study was to investigate post-operative pain intensity, analgesic consumption and the incidence of chronic pain in women after different types of breast cancer surgery. Patients were randomized to either patient-controlled analgesia or nurse-administered analgesia. Opioid-consumption was registered for 24 h. A division of the patient-material into four subgroups was performed: (1) mastectomy; (2) mastectomy and axillary lymph node dissection; (3) mastectomy and reconstruction; and (4) mastectomy, reconstruction and axillary lymph node dissection. Visual analogue scale was used to measure pain intensity. Four years after surgery, a questionnaire regarding persistent pain was completed. Patients undergoing reconstruction scored higher pain levels than the others. Patient-controlled analgesia provided better pain relief but also considerably higher consumption of opioids by the women who underwent breast reconstruction. The incidence of remaining pain was 25% after 3-4 years. Immediate breast reconstruction causes severe post-operative pain that can respond poorly to opioids. Chronic pain after breast cancer surgery is common and should be further analysed aiming at better prevention and treatment options.

Clinical Trial↗

Breast Surgery International--breast cancer in developing countries.

Breast Surgery International (BSI) was formed in 1999 as an integrated society within the International Surgical Society ISS/SIC. One goal is to promote breast surgery world wide and focus on the situation in the developing countries. An edited summary of a symposium on locally advanced breast cancer (LABC) and the current situation in two African countries and in Malaysia is reported. Diagnosis, management and treatment options differ from recommendations that prevail due to lack of resources, lack of access to facilities and cultural and socioeconomic barriers. Younger age at onset, more men are affected and locally advanced breast cancer dominates the clinical panorama. A rational treatment plan for LABC should have chemotherapy, surgery, radiotherapy and hormonal therapy as armaments. A unique opportunity exists for international interchange within a professional organization such as BSI, for providing training opportunities, for clinical and experimental studies of the world' s most common female malignancy.

Breast Neoplasms↗

Trace elements in two pulverized coal-fired power stations.

Beside major pollutants (particulates, carbon, sulfur, and nitrogen oxides), coal combustion generates emissions of potentially toxic trace elements. The current work focuses on predicting the fate of eight trace elements (As, Cd, Hg, Ni, Pb, Se, V, and Zn) in power stations that fire pulverized coal and are equipped with flue gas scrubbers. The core of the study is global equilibrium analysis carried out with the aid of three extensive databases. The first set of equilibrium constants describes conditions prevailing in the furnace and the flue gas duct, while the second set describes reactions in the flue gas scrubber. Melting behavior of ash and solubility of trace elements within the slag are described as a third set of data. To test the modeling approach taken in this paper, the predicted overall partitioning of trace elements is compared with measured data from two full-scale facilities. The results of the study indicate that As, Cd, Ni, Pb, V, and Zn are captured in the fly ash, and that the fate of these element correlates with the overall particle capture of the power plants. Calculations for the flue gas scrubber facilities show that nonvolatile trace elements are likely to dissolve in the scrubber solution, and that capture of these elements likewise is correlated with the overall particulate behavior. Theoretical predictions of the melting behavior indicate that As, Ni, Zn, and to some extent Pb are likely to dissolve in the molten ash.

Air Pollutants↗

Flow cytometric enumeration of micronucleated reticulocytes: high transferability among 14 laboratories.

This laboratory previously described a single-laser flow cytometric method, which effectively resolves micronucleated erythrocyte populations in rodent peripheral blood samples. Even so, the rarity and variable size of micronuclei make it difficult to configure instrument settings consistently and define analysis regions rationally to enumerate the cell populations of interest. Murine erythrocytes from animals infected with the malaria parasite Plasmodium berghei contain a high prevalence of erythrocytes with a uniform DNA content. This biological model for micronucleated erythrocytes offers a means by which the micronucleus analysis regions can be rationally defined, and a means for controlling interexperimental variation. The experiments described herein were performed to extend these studies by testing whether malaria-infected erythrocytes could also be used to enhance the transferability of the method, as well as control intra- and interlaboratory variation. For these studies, blood samples from mice infected with malaria, or treated with vehicle or the clastogen methyl methanesulfonate, were fixed and shipped to collaborating laboratories for analysis. After configuring instrumentation parameters and guiding the position of analysis regions with the malaria-infected blood samples, micronucleated reticulocyte frequencies were measured (20,000 reticulocytes per sample). To evaluate both intra- and interlaboratory variation, five replicates were analyzed per day, and these analyses were repeated on up to five separate days. The data of 14 laboratories presented herein indicate that transferability of this flow cytometric technique is high when instrumentation is guided by the biological standard Plasmodium berghei.

Animals↗

Patterns of chromosomal imbalances in parathyroid carcinomas.

In this study we have characterized chromosomal imbalances in a panel of 29 parathyroid carcinomas using comparative genomic hybridization (CGH). The most frequently detected imbalances were losses of 1p and 13q that were seen in >40% of the cases. The commonly occurring regions of loss were assigned to 1p21-p22 (41%), 13q14-q31 (41%), 9p21-pter (28%), 6q22-q24 (24%), and 4q24 (21%), whereas gains preferentially involved 19p (45%), Xc-q13 (28%), 9q33-qter (24%), 1q31-q32 (21%) and 16p (21%). The distribution of CGH alterations supports the idea of a progression of genetic events in the development of parathyroid carcinoma, where gains of Xq and 1q would represent relatively early events that are followed by loss of 13q, 9p, and 1p, and by gain of 19p. A sex-dependent distribution was also evident for two of the common alterations with preferential gain of 1q in female cases and of Xq in male cases. When the CGH profiles for the 29 carcinomas were compared with our previously published results for sporadic parathyroid adenomas, highly significant differences were revealed. Loss of 1p, 4q, and 13q as well as gains of 1q, 9q, 16p, 19p and Xq were significantly more common in the carcinomas than in the adenomas. In contrast, loss of the 11q13 region, which is the most common CGH abnormality in sporadic adenomas, was not detected in any of the carcinomas. Taken together, the findings identify several candidate locations for tumor suppressor genes and oncogenes that are potentially involved in parathyroid carcinogenesis.

Adenoma↗

Initial experiences of women from hereditary breast cancer families after bilateral prophylactic mastectomy: a retrospective study.

BACKGROUND: Women from families with breast and/or ovarian cancers seek advice and counselling for risk assessment, but they also want information about preventive measures that might reduce their risk of developing these neoplasms. PATIENTS AND METHODS: This study was undertaken in order to assess 15 women's experience with the decision-making process prior to undergoing prophylactic bilateral mastectomy (PM) and immediate breast reconstruction (IBR). It was also designed to determine the degree of the women's satisfaction with the information delivered by the different caregivers, and whether the women felt that their need for psychosocial support was appropriately met. An additional goal was to learn about the patients>> satisfaction with the operations. RESULTS: The women found it difficult to translate the genetic information transmitted to them, although they were satisfied by the way it was given. At some stage during the pre-operative and post-operative period nearly all women stated that they lacked psychological support from the different caregivers. No woman regretted her choice to undergo PM and IBR. By far, the most important issue was the actual risk reduction. However, the result exceeded all patients' initial expectations. When performing PM and IBR, a multidisciplinary team approach, including a psychologist, seems mandatory. It will facilitate the overall management of this group of women.

Adult↗

Evaluation of retinoblastoma and Ki-67 immunostaining as diagnostic markers of benign and malignant parathyroid disease.

Assessment of the malignant potential of parathyroid tumors in the absence of metastases can be difficult using morphologic criteria alone. In this study we have examined a total of 58 parathyroid tumors (31 benign, 15 malignant, and 12 equivocal) from 54 patients using immunohistochemistry with monoclonal antibodies directed against the retinoblastoma (RB) protein and the cell cycle-associated antigen Ki-67 to evaluate their role as diagnostic markers. RB protein immunoreactivity was not useful for distinguishing between benign and malignant parathyroid tumors. Analysis of the proliferation marker Ki-67 showed that there was a trend toward more intense staining in the malignant cases. The Ki-67 labeling index was highest in the parathyroid cancers (median 33) and lowest in the sporadic primary adenomas (median 2). An observation that might have clinical implications is that tumors from patients with familial hyperparathyroidism linked to chromosome 1q showed a high Ki-67 index, indicating strong proliferative activity (median 25). This correlates well with the clinical observation of tumors with malignant potential in this syndrome. Because of the considerable overlap between groups of tumors, Ki-67 is not suitable for definitive differentiation between benign and malignant tumors. However, Ki-67 may give valuable information about which patients should be followed more closely.;1999>

Antibodies, Monoclonal↗

Expression of matrix metalloproteinase gelatinase A messenger ribonucleic acid in parathyroid carcinomas.

BACKGROUND: The incidence of parathyroid cancer in patients with hyperparathyroidism is less than 1%. However, these few cases cause diagnostic problems in the absence of clear-cut invasion of adjacent organs or metastasis. New markers are needed to increase diagnostic accuracy. METHODS: Thirty-one parathyroid tumors from patients with primary hyperparathyroidism were collected worldwide. Eighteen tumors were classified as unequivocal cancers, whereas 13 tumors were considered equivocal because of a lack of infiltrative growth or evidence of recurrence. Paraffin sections were hybridized with a 35S-labeled riboprobe complementary to gelatinase A mRNA, dipped in photographic emulsion, developed, counterstained, and then evaluated by light- and dark-field microscopy. RESULTS: Fourteen of the 18 unequivocal parathyroid cancers expressed gelatinase A, as compared with the equivocal tumors, of which only 4 of 13 showed expression. The strongest hybridization signal was seen in stromal cells at the tumor border, most likely fibroblasts and macrophages. No expression was detected in tumor cells. CONCLUSIONS: Invasive growth of many tumors is facilitated by proteolytic enzymes, such as gelatinase A. The presence of gelatinase A mRNA in parathyroid tumors strengthens the suspicion of malignancy but cannot be used as a definitive marker of malignancy.

Adult↗

Alternative genetic pathways in parathyroid tumorigenesis.

In this study 44 parathyroid tumors from 26 sporadic cases, 10 cases previously given irradiation to the neck, and 8 familial cases were screened for sequence copy number alterations by comparative genomic hybridization. In the sporadic adenomas, commonly occurring minimal regions of loss could be defined to chromosome 11 (38%), 15q15-qter (27%), and 1p34-pter (19%), whereas gains preferentially involved 19p13.2-pter (15%) and 7pter-qter (12%). Multiple aberrations were found in sporadic tumors with a somatic mutation and/or loss of heterozygosity of the MEN1 gene. The irradiation-associated tumors also showed multiple comparative genomic hybridization alterations and frequent losses of 11q (50%), and subsequent analysis of the MEN1 gene demonstrated mutations in 4 of 8 cases (50%). The adenomas from familial cases showed few alterations, and in 3 of these tumors a gain of 19p13.2-pter was seen as the only aberration. In this study numerical copy number alterations were frequently detected in sporadic and irradiation-associated parathyroid adenomas, although these tumors are benign. The majority of these alterations were found in tumors with confirmed involvement of the MEN1 gene locus in agreement with a role of the MEN1 gene in genomic stability. Furthermore, the frequent occurrence of MEN1 mutations (50%) in irradiation-associated parathyroid tumors suggests that inactivation of the MEN1 gene is an important genetic alteration involved in the development of parathyroid tumors in postirradiation patients.

Adenoma↗