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Biomedical subjects

K Sandelin

Publications and source records attributed to K Sandelin.

At least 37 records · Page 2Linked to original sources
PubMed1998

Management, morbidity, and oncologic aspects in 100 consecutive patients with immediate breast reconstruction.

BACKGROUND: Immediate breast reconstruction (IBR) is indicated when breast-conserving surgery is inappropriate and the patient refuses mastectomy as the sole procedure. METHODS: Management, morbidity, and oncologic aspects were studied in 100 consecutive patients treated between 1990 and 1994 with a minimum follow-up time of 2 years. Indications for mastectomy and IBR always were discussed within a multidisciplinary group. Eighty-four patients had primary breast cancer, 12 patients underwent salvage mastectomy for an ipsilateral breast tumor recurrence, two patients had benign breast disease, and two patients underwent prophylactic mastectomy because of familial breast cancer. RESULTS: Saline and silicone gel-filled implants were used predominantly (88%), but free and pedicled TRAM flaps were performed in 12 patients (12%). The overall complication rate was 16%. Seven patients lost their implants, three of whom had been irradiated to the chest wall. Sixty-five patients completed breast reconstruction (nipple and areola) within a median time of 418 days (range 40 to 1471 days). At follow-up, eight patients had locoregional recurrences after a median time of 7.2 months (range 1 to 23 months), and nine patients had died from disseminated breast cancer. CONCLUSION: IBR is time-consuming, but it is well tolerated and does not interfere with oncologic adjuvant treatment. IBR can be performed with low morbidity by a dedicated multidisciplinary team.

Abdominal Muscles↗
PubMed1998

Outcome of treatment for ipsilateral breast tumor recurrence in early-stage breast cancer.

INTRODUCTION: The aims of the study were to assess the outcome among patients with early breast cancer operated on with wide local excision who developed a subsequent ipsilateral breast tumor recurrence, and to identify risk factors for uncontrolled local disease. Uncontrolled local disease (ULD) was defined as the appearance of clinically manifest invasive adenocarcinoma in the remaining breast or on the ipsilateral chest wall which could not be eradicated with salvage treatment during the period of follow-up (2-18 years). PATIENTS AND METHODS: Eighty-five patients in a cohort of 759 patients, treated for invasive Stage I-II breast cancer with breast-conserving surgery 1976-1985 in Stockholm, with a subsequent ipsilateral breast tumor recurrence (IBTR) were reviewed retrospectively. The majority of the patients were premenopausal (58%), node negative (72%), and had received postoperative radiotherapy (79%). Median follow-up time following breast-conserving surgery was 13 (9-19) years. Multivariate Cox's hazard regression was used in the statistical analysis to identify prognostic factors for ULD. RESULTS: The majority (n = 61) of the IBTR's were located in the original tumor quadrant and showed the same histopathological features as the primary tumor. Salvage mastectomy (n = 65) or reexcision (n = 14) were performed in 79 (93%) of the patients. Twenty-one patients developed ULD. Five years following the diagnosis of IBTR the disease-free survival was 59%, the cumulative incidence for ULD was 24%, and for death in breast cancer 34%. In the cohort of 759 patients, patients who received radiotherapy following the primary breast-conserving surgery had 1% cumulative incidence of ULD following the diagnosis of IBTR compared to 4% among patients that received no postoperative radiotherapy. The cumulative incidence at 5 years of ULD following salvage mastectomy was 12% compared to 33% after salvage reexcision. Patients operated on with breast-conserving surgery with an original tumor size < 15 mm, who were treated with salvage mastectomy for IBTR, had in multivariate analysis the lowest relative risk for ULD. Adjuvant chemotherapy following IBTR treatment did not seem to improve local tumor control. Following the diagnosis of IBTR, 78% (n = 21) of the patients with ULD and/or regional recurrence (n = 27), died of a disseminated breast cancer in contrast to 10% (n = 6) among the remaining 58 patients. CONCLUSION: Uncontrolled local disease is an important outcome measure following breast-conserving surgery. In this cohort, salvage mastectomy provided a superior local control rate compared to salvage reexcision. A higher although not statistically significant rate of ULD was also seen in patients who had not received postoperative radiotherapy as part of their primary treatment.

Antineoplastic Agents, Hormonal↗
PubMed1998

Decreased expression of calcium-sensing receptor messenger ribonucleic acids in parathyroid adenomas.

BACKGROUND: The set point for parathyroid hormone (PTH) secretion is increased in patients with primary hyperparathyroidism, possibly because of receptor defect(s). A decreased expression of calcium receptor (CaR) messenger ribonucleic acid (mRNA) and protein and a decreased expression of the putative calcium-sensing CAS (gp330/megalin) protein have been demonstrated in parathyroid adenomas. METHODS: Expression of CAS mRNA was studied in matched pairs of adenomas and adenoma-associated biopsy specimens from normal parathyroid glands from 15 patients with sporadic primary hyperparathyroidism. Cryostat sections were hybridized with an oligonucleotide complementary to CAS mRNA, rinsed, air dried, and exposed to x-ray film for semiquantification of radioactivity. RESULTS: Expression of CAS mRNA in the adenomas was lowered significantly to 25% (median; range 9% to 80%) of that of the corresponding biopsy specimens of normal parathyroid glands. No correlation was seen between CAS mRNA in the adenoma and preoperative serum calcium levels, PTH level, or weight of the adenoma. The levels of CAS mRNA were significantly lower than those observed previously for CaR mRNA. There was no significant correlation between the levels of CAS and CaR mRNA. CONCLUSIONS: Lowered levels of receptors sensing extracellular calcium (CaR and CAS) probably contribute to the increased set point for PTH secretion in primary hyperparathyroidism.

Adenoma↗
PubMed1998

Technical aspects of immediate breast reconstruction--two year follow-up of 100 patients treated consecutively.

We report the technical aspects of immediate breast reconstruction of the first 100 consecutive patients done at the Karolinska Hospital. Two patients had bilateral cancer. Preoperative chemotherapy had been given to five patients and postoperative chemotherapy to 13 patients. In 96 patients the indication was breast carcinoma. Mean tumour size was 13.1 mm and always less than 100.0 mm. Radiotherapy had been given preoperatively in nine patients and postoperatively in 10 patients. Mean operation time was 127 minutes, and median operating time 100 minutes. Hospital stay was five days. Breast reconstructions were performed with permanent prostheses in 22, expanders in 66, pedicled TRAM flaps in eight, and free TRAM flaps in four patients. To complete the breast reconstruction one major and 1.4 minor operations were needed. Total time to reconstruction was 461 days. The overall complication rate was 16%, with 13 local complications. Three developed haematomas, seven lost their implants, two developed partial necroses of pedicled TRAM flaps, and one developed abdominal bulging after a free TRAM flap. Patients were followed up after 2.0-5.7 years. The capsular contracture rate in the implant group was 24%.

Adult↗
PubMed1998

Familial isolated hyperparathyroidism maps to the hyperparathyroidism-jaw tumor locus in 1q21-q32 in a subset of families.

Approximately 70 families with familial isolated hyperparathyroidism (FIHP) have been reported. Whether it is a separate entity or a variant of multiple endocrine neoplasia type 1 (MEN1 at 11q13) or hyperparathyroidism-jaw tumor (HPT-JT or HRPT2 at 1q21-32) syndrome is not known. We describe here 3 unreported families with familial primary hyperparathyroidism and evaluate their clinical, pathological, and genetic profiles. Biochemical and radiological screenings for MEN1 were negative for all families. In 2 families with a total of 10 affected cases and 3 female obligate carriers, there is no evidence of jaw or renal lesions despite careful radiological investigations. In both families the disease was linked to the 1q21-q32 region with the maximum logarithm of the odds (lod) scores of 3.10 and 3.43 for markers D1S222 and D1S249 respectively, at recombination fraction of 0. In 1 family 2 types of parathyroid pathology were found: 3 of chief cell type and 1 of oxyphil/oncocytic cell type. Two chief cell tumors and 1 oxyphil tumor were found to have loss of heterozygosity (LOH) involving loss of the wild-type alleles for chromosome 1q markers. In the third family, with 4 affected siblings, a parathyroid carcinoma and 2 cases of polycystic kidney disease were found. The parathyroid carcinoma also showed loss of heterozygosity in the 1q region. In conclusion, we found that the hyperparathyroidism traits in a subset of FIHP families are linked to the 1q21-32 markers in the HRPT2 region. We describe the spectrum of parathyroid disease in 1q-linked families involving 3 different types of pathology and demonstrate for the first time loss of wild-type alleles in these parathyroid tumors. Taken together, the results suggest that some of the FIHP are a variant of HPT-JT and that the gene involved is a tumor suppressor gene.

Adult↗
PubMed1998

Alterations of the MEN1 gene in sporadic parathyroid tumors.

Primary hyperparathyroidism is a common endocrine disease that also occurs in a number of inherited disorders, including multiple endocrine neoplasia type 1 (MEN1). Loss of heterozygosity (LOH) in the MEN1 region on chromosome 11q13 has been found in 30% of sporadic parathyroid tumors, making the recently cloned MEN1 gene a prime candidate for involvement in parathyroid tumorigenesis. Using LOH and single strand conformation analysis, we screened 45 sporadic tumors from 40 patients for alterations involving the MEN1 gene. Thirteen tumors showed LOH at 11q13, and in 6 of these cases, somatic mutation of the MEN1 gene was detected. In tumors without LOH, no mutations were detected. The mutations consisted of 3 small deletions, 1 insertion, and 2 missense mutations that had not been reported in MEN1 patients or parathyroid tumors previously. Using messenger ribonucleic acid in situ hybridization, the expression of the MEN1 gene was studied. There was no difference in expression between normal and tumor tissue. In conclusion, the findings of inactivating mutation in tumors with LOH at 11q13 confirm the role of the MEN1 tumor suppressor gene in a subset of sporadic parathyroid tumors.

Adult↗
PubMed1997

A screening for BRCA1 mutations in breast and breast-ovarian cancer families from the Stockholm region.

To identify BRCA1 germ-line mutations in the breast and breast-ovarian cancer families in the Stockholm region, a total of 127 families were screened. DNA from 174 patients from these families were studied using various mutation screening techniques, followed by direct DNA sequencing. Mutations were identified in 7 of 20 families with breast and ovarian cancer and in one family with ovarian cancer only, whereas only 1 family of 106 with breast cancer showed a mutation. Thus, germ-line mutations in BRCA1 were found in one-third of the families with both breast and ovarian cancer, but in only 1% of the breast cancer families. The low frequency of germ-line mutations in the site-specific breast cancer families means that other genes are likely to segregate in these families.

Breast Neoplasms↗
PubMed1997

Differential loss of heterozygosity in familial, sporadic, and uremic hyperparathyroidism.

Various genetic loci harboring oncogenes, tumor suppressor genes, and genes for calcium receptors have been implicated in the development of parathyroid tumors. We have carried out loss of heterozygosity (LOH) studies in chromosomes 1p, 1q, 3q, 6q, 11q, 13q, 15q, and X in a total of 89 benign parathyroid tumors. Of these, 28 were sporadic parathyroid adenomas from patients with no family history of the disease, 41 were secondary parathyroid tumors, 5 were from patients with a history of previous irradiation to the neck, 12 were from patients with a family history of hyperparathyroidism, and 3 were parathyroid tumors related to multiple endocrine neoplasia type 1 (MEN1). In addition, we determined the chromosomal localization of a second putative calcium-sensing receptor, CaS, for inclusion in the LOH studies. Based on analysis of somatic cell hybrids and fluorescent in situ hybridization to metaphase chromsomes, the gene for CaS was mapped to chromosomal region 2q21-q22. The following results were obtained from the LOH studies: (1) out of the 24 tumors that showed LOH, only 4 had more than one chromosomal region involved, (2) in the tumors from uremic patients, LOH of chromosome 3q was detected in a subset of the tumors, (3) LOH of the MEN1 region at 11q13 was the most common abnormality found in both MEN1-related and sporadic parathyroid tumours but was not a feature of the other forms of parathyroid tumors, (4) LOH in 1p and 6q was not as frequent as previously reported, and (5) tumor suppressor genes in 1q and X might have played a role, particularly on the X chromosome, in the case of familial parathyroid adenomas. We therefore conclude that the tumorigenesis of familial, sporadic, and uremic hyperparathyroidism involves different genetic triggers in a non-progressive pattern.

Adenoma↗
PubMed1997

Breast conserving surgery for invasive breast cancer: risk factors for ipsilateral breast tumor recurrences.

To identify risk factors associated with an increased risk for ipsilateral breast tumor recurrence following breast-conserving surgery, a cohort of 759 women with T1-T2 tumors were studied. The majority of the patients (88%) had received postoperative radiation therapy to the breast. Median follow-up time was 10 (range: 6-17) years. There was a 1-1.5% yearly increase in ipsilateral breast tumor recurrences. For women < 50 ys the cumulative recurrence rate at 10 years was 18% and for women > or = 50 ys, 9%. Node positive women had a cumulative breast recurrence rate of 25% versus 10% for node negative women. Ten years postoperatively, irradiated patients had a cumulative recurrence rate of 11% versus 26% when no irradiation was given. The beneficial effect of radiotherapy was substantial during the first four postoperative years. The relative risk for an ipsilateral breast tumor recurrence during this period was 4.5 times higher than for non-irradiated patients. However, the protective effect of radiotherapy decreased with time. After ten years the relative risk of ipsilateral breast tumor recurrence was the same among irradiated and non-irradiated patients although the number of events during this period was low. Univariate analysis showed that seven factors were significantly associated with an increased risk of ipsilateral breast tumor recurrence, namely age < 50 ys, increasing tumor size, uncertain microscopic margins, axillary lymph node metastases, no postoperative tamoxifen treatment, premenopausal status, and no postoperative radiotherapy. Three factors remained independently significant after multivariate analysis: age < 50 ys, no postoperative radiation therapy, and positive lymph nodes. In conclusion, radiotherapy reduced the breast recurrence rate, but the effect decreased with time. Node-negative women > or = 50 were a low risk-group for ipsilateral breast tumor recurrence, with a cumulative risk at 10 years of 9% without radiation therapy and 5% with breast irradiation.

Adult↗
PubMed1997

Apoptosis and growth factors in parathyroid adenomas.

Detection of apoptotic cells and of immunoreactivity to transforming growth factor alpha (TGF-alpha) and to its ligand, epidermal growth factor receptor (EGFR), was studied in 20 cases of parathyroid adenoma. The DNA nick-end labelling method revealed that 85% of these adenomas contained apoptotic cells. Detection rates of TGF-alpha and EGFR were very high, but neither TGF-alpha nor EGFR was correlated to apoptosis. As TGF-alpha exerts its effect via EGFR, the concomitant demonstration of the two factors occurring in both the adenomatous tissue and the surrounding rim of normal tissue may reflect a significant mutual association. The markers were located mainly within the cytoplasm, indicating their important role in growth regulation, cell differentiation and cell function. The synchronous expression of TGF-alpha and EGFR in both parathyroid adenomas and normal glandular parenchyma suggests that these functions may be mediated by an autocrine mechanism.

Adenoma↗
PubMed1997

Multiple endocrine neoplasia type 1 and the search for the genetic trigger.

Multiple endocrine neoplasia type 1 (MEN-1) is characterized by primary hyperparathyroidism, endocrine pancreatic-duodenal and anterior pituitary tumors. The diagnosis is challenging and involves the exclusion of other endocrine neoplasia syndromes with overlapping features. The predisposing genetic defect was assigned to chromosomal region 11q13 based on linkage analysis. Combined tumor and pedigree genotype analysis showed that allele losses in pancreatic, parathyroid and pituitary tumors eliminated the wild-type allele at the 11q13 loci, suggesting inactivation of a tumor suppressor gene in this region. A 5-Mb integrated map of the region has been established by the European consortium on MEN-1. Based on this mapping the critical interval was restricted to 2 Mb, a region within which eight candidate genes are located.

Chromosome Mapping↗
PubMed1996

Patients' psychological and cosmetic experience after immediate breast reconstruction.

Immediate breast reconstruction was introduced in 1990 at the Karolinska Hospital. A semistructured interview with 20 patients operated on between 1991 and 1994 was undertaken to evaluate patients' degrees of satisfaction regarding pre-operative information, the need for psychological support and the opinion about the cosmetic outcome. During the pre-operative period, 18 patients felt that they were engaged in the decision-making whereas two patients felt that the surgeon alone was responsible for the decision. Regarding pre-operative information given, 7/20 were satisfied, 5/20 were mostly satisfied, 5/20 were unsatisfied and 3/20 had no opinion. During the early post-operative period (<3 months), five patients felt anxiety or depression and 10 patients felt a need of additional psychological support. Within 6 weeks 19/20 patients returned to their occupational level. During the late post-operative period (>3 months), 19/20 patients were generally satisfied with the reconstructive procedure. Eight patients thought the final result exceeded their initial expectations and 11/17 accepted the new breast as an integrated part of their body. The results confirm that immediate breast reconstruction plays an important role in the surgical management of breast cancer. The need for pre-operative information and continuous psychological support in terms of an empathetic behaviour cannot be underestimated.

Adult↗
PubMed1996

Mammographic features, predictors of early ipsilateral breast tumour recurrences?

Mammograms from 69 patients with Stage I/II breast cancer, operated on using breast-conserving surgery between 1987-1990 were blindly re-evaluated in order to predict retrospectively ipsilateral breast tumour recurrences. The study cohort was divided into two groups of 34 and 35 patients. Each group was matched according to age, the time at risk and to presence or absence of an ipsilateral breast tumour recurrence. The mammographic reinterpretation was performed by two radiologists that correctly predicted an ipsilateral breast tumour recurrence in 81%. Mammographic characteristics, such as diffuse microcalcifications, multifocality, solitary densities, especially of stellate type near the nipple and/or spicula in the vicinity of the retroareolar region were more often associated with an ipsilateral breast tumour recurrence. Data from this limited series suggest that certain mammographic features seem to correlate with the ability of the tumour to recur locally. Hence, mammography can play a prognostic role in deciding the treatment of choice in operable breast cancer.

Adult↗
PubMed1995

Undescended superior parathyroid gland: a potential cause of failed cervical exploration for hyperparathyroidism.

BACKGROUND: The undescended inferior parathyroid gland is a well-established although infrequent embryologic abnormality resulting in an ectopically located gland usually associated with thymic tissue and is found most commonly within the carotid sheath at the level of the carotid bifurcation. Embryologically undescended superior glands (either normal or enlarged), clearly above the level of the upper pole of the thyroid gland and found within or in approximation to the lateral pharyngeal wall, have not been previously described. METHODS: The locations of all parathyroid glands at the time of cervical exploration were carefully examined as to embryologic origin in a combined experience of more than 3000 patients with primary or secondary hyperparathyroidism. RESULTS: Five patients had enlarged abnormal glands located within or in close approximation to the pharyngeal wall. All were above the upper pole of the thyroid gland. Two were identified at reoperation on the basis of localization studies. One gland was found after resection of a massive concomitant cervical goiter. The other two were found after an extensive search for a superior gland. CONCLUSIONS: Undescended superior glands are extremely rare (0.08%). They are located within or in approximation to the pharynx above the level of the thyroid gland with an unusual blood supply, which supports an embryologic rather than acquired cause for their ectopic location.

Adolescent↗
PubMed1995

Peroperative adenosine infusion reduces the requirements for isoflurane and postoperative analgesics.

The aims of this study were to investigate the influence of adenosine infusion, firstly, on postoperative analgesic requirements, and secondly, on peroperative isoflurane requirements. Seventy-five women, aged 18-70 yrs, ASA grades I and II, scheduled for breast surgery, were randomly assigned to peroperatively receive a double-blind intravenous infusion of either adenosine, 80 micrograms.kg-1.min-1, or placebo, during surgery under isoflurane/N2O/O2 anesthesia. The peroperative isoflurane requirements were significantly reduced at 30 and 90 min of surgery during adenosine treatment. The number of patients reporting pain when regaining consciousness after surgery was reduced by 57% in the adenosine group, 8/31 vs 19/32 (P < 0.02). Further, the postoperative 24-h opioid requirements were reduced by 27% in the adenosine group (P < 0.03). In conclusion, we found that a peroperative infusion of a small dose of adenosine during breast surgery, reduces the peroperative anesthetic requirements, and the demand for post-operative analgesics.

Adenosine↗