Effect of exercise on mobility, balance, and health-related quality of life in osteoporotic women with a history of vertebral fracture: a randomized, controlled trial.

UNLABELLED: The aim of this randomized controlled trial was to evaluate the effect of a 3-month course of exercises on mobility, balance, disease-specific, and generic health-related quality of life (HRQOL) for women with osteoporosis and a history of vertebral fractures. Our results showed that exercises improved their mobility, balance, and HRQOL. INTRODUCTION: The aim was to evaluate the effect of a 3-month course of circuit exercises plus a 3-h lesson on how to cope with osteoporosis on mobility, balance, and the HRQOL for postmenopausal women (60-84 years) with osteoporosis and a history of vertebral fracture. Our hypothesis was that a 3-month course would have a significantly positive effect on the women's mobility and balance as well as on their HRQOL. METHODS: The participants (89) were randomized to an intervention group (IT) or a control group (CT) and assessed at baseline at 3 months and at 12 months with measurement of maximum walking speed (MWS), Timed Up and GO (TUG), Functional Reach (FR), the Quality of Life Questionnaire issued by the European Foundation for Osteoporosis ('QUALEFFO-41') and the General Health Questionnaire (GHQ-20). The sample size was calculated with reference to walking speed (primary outcome), and the statistical approaches used were Student's t test or the chi-square test. RESULTS: At 3 months, better results were registered on the primary outcome, MWS as well as TUG, FR, sum score of GHQ-20, and "QUALEFFO-41: mental function" in the IT compared with the CT. At 12 months, those in the IT had a better result on the primary outcome, MWS as well as TUG, "QUALEFFO-41: total score" "QUALEFFO-41: mental function", "QUALEFFO-41: physical function", and "QULEFFO-41: pain" compared with CT. CONCLUSION: Circuit exercises will improve mobility and health-related quality of life of elderly women with osteoporosis and a history of vertebral fractures.

CYP17 and breast cancer risk: the polymorphism in the 5' flanking area of the gene does not influence binding to Sp-1.

The ability of a motif of the CYP17 5' untranslated region, created by a polymorphic T to C substitution, to bind to the human transcription factor Sp-1 was investigated. No binding of any of the polymorphic alleles was observed in electromobility shift assay. No other sequence within +1 to +100 of each of the CYP17 alleles formed complex with the Sp-1 or enhanced binding to the polymorphic CACC box. Genotyping of 510 breast cancer patients and 201 controls revealed no difference in genotype frequencies. Age at onset, tumor grade, lymph node status and distant metastases, stage, and estrogen and progesterone receptor status were not associated with the CYP17 genotype.

Genetic variants of CYP19 (aromatase) and breast cancer risk.

The effect of a SNP in exon 10 of CYP19 on tumor mRNA levels and splice variants were studied and correlated with clinical parameters and risk of breast cancer. In the vast majority of breast cancers, the estrogen levels modulate the tumor growth and depend on the activity of CYP19. Patients (n=481) and controls (n=236) were genotyped by T-tracks in a single sequencing reaction (SSR). The frequency of TT genotypes was significantly higher in patients versus controls (P=0.007) particularly among those with stage III and IV disease (P=0.004) and with tumors larger than 5 cm (P=0.001). A significant association between presence of the T allele and the level of aromatase mRNA in the tumors was observed (P=0.018), as well as with a switch from adipose promoter to ovary promoter (P=0. 004). Previously, we reported a rare polymorphic allele of CYP19 (repeat (TTTA)12) to be significantly more frequent in breast cancer patients than in controls. Here we describe another polymorphism, a C - T substitution in exon 10 of the CYP19 gene which is in strong linkage disequilibrium with the (TTTA)n polymorphism but with higher frequency of the variant allele. Our data suggest that the T-allele of the CYP19 gene is associated with a 'high activity' phenotype. Oncogene (2000) 19, 1329 - 1333.

Detection of isolated tumor cells in bone marrow is an independent prognostic factor in breast cancer.

PURPOSE: This study was performed to disclose the clinical impact of isolated tumor cell (ITC) detection in bone marrow (BM) in breast cancer. PATIENTS AND METHODS: BM aspirates were collected from 817 patients at primary surgery. Tumor cells in BM were detected by immunocytochemistry using anticytokeratin antibodies (AE1/AE3). Analyses of the primary tumor included histologic grading, vascular invasion, and immunohistochemical detection of c-erbB-2, cathepsin D, p53, and estrogen receptor (ER)/progesterone receptor (PgR) expression. These analyses were compared with clinical outcome. The median follow-up was 49 months. RESULTS: ITC were detected in 13.2% of the patients. The detection rate rose with increasing tumor size (P =.011) and lymph node involvement (P <.001). Systemic relapse and death from breast cancer occurred in 31.7% and 26.9% of the BM-positive patients versus 13.7% and 10.9% of BM-negative patients, respectively (P <.001). Analyzing node-positive and node-negative patients separately, ITC positivity was associated with poor prognosis in the node-positive group and in node-negative patients not receiving adjuvant therapy (T1N0). In multivariate analysis, ITC in BM was an independent prognostic factor together with node, tumor, and ER/PgR status, histologic grade, and vascular invasion. In separate analysis of the T1N0 patients, histologic grade was independently associated with both distant disease-free survival (DDFS) and breast cancer-specific survival (BCSS), ITC detection was associated with BCSS, and vascular invasion was associated with DDFS. CONCLUSION: ITC in BM is an independent predictor of DDFS and BCSS. An unfavorable prognosis was observed for node-positive patients and for node-negative patients not receiving systemic therapy. A combination of several independent prognostic factors can classify subgroups of patients into excellent and high-risk prognosis groups.

Detection of isolated tumor cells in bone marrow in early-stage breast carcinoma patients: comparison with preoperative clinical parameters and primary tumor characteristics.

UNLABELLED: PURPOSE/EXPERIMENTAL DESIGN: The importance of detection of disseminated isolated tumor cells (ITCs) in bone marrow (BM) is still not settled. BM aspirates from 920 patients with primary breast cancer were analyzed for tumor cells by standardized direct immunocytochemical analysis (ICC) of 2 x 10(6) mononuclear cells (MNCs) using anticytokeratin monoclonal antibody (AE1/AE3). Samples (637) were analyzed by negative immunomagnetic enrichment (IMS) followed by ICC (10 x 10(6) MNCs). Analyses of the primary tumor specimens have been performed, including histomorphology, tumor-node-metastasis (TNM) staging, grading, and immunohistochemical analyses. RESULTS: Of the patients with infiltrating carcinoma, 63% were node negative (N0) and 33%, node positive (N+). The results show the presence of tumor cells in 13.4% of the evaluable patients after direct ICC analysis. The presence of tumor cells correlated to the nodal- and tumor stage, showing BM positivity in 9.9% of the N0 cases and 20.6% in the N+ group (P < 0.0005), 11.2% of the stage T(1) were positive, and 15.0% and 22.6% were positive in the T(2) and T(3/4) groups, respectively (P = 0.013). No correlation between detection of ITC and detection of p53 and cathepsin D expression was found. Vascular invasion and c-erbB2 expression were associated with ITCs in BM (P = 0.045 and P = 0.024, respectively). Node-negative patients with estrogen receptor (ER)+ and/or progesterone receptor (PgR)+ tumors had lower frequency of ITCs than ER-/PgR- (P = 0.004). The use of negative IMS increased the frequency of positive BM by 63% (P < 0.0005). CONCLUSIONS: The direct ICC detection of ITCs in BM correlated with primary tumor stage, nodal stage, vascular invasion, c-erbB2 expression, and ER/PgR status. Analysis of larger BM samples by negative IMS resulted in increased number of ITC-positive patients.

Expression of E-cadherin and its relation to the p53 protein status in human breast carcinomas.

In breast carcinomas the TP53 gene is altered in 10-30% of cases. Alteration of the gene may lead to a general genomic instability, detected as deletions and/or amplifications at the gene level, and as altered expression at the mRNA and protein level. We have demonstrated a strong association between down-regulation of E-cadherin protein expression and alterations of the p53 protein, detected as TP53 gene mutation and/or protein accumulation in tumour samples from 210 patients with breast carcinomas (P < 0.001). Investigation of allelic imbalance using microsatellite markers located near the E-cadherin locus was also performed. A higher frequency of loss of heterozygosity in the microsatellite marker closest to the E-cadherin locus was observed in samples with down-regulation of E-cadherin protein expression. A higher frequency of down-regulation of the E-cadherin protein expression was found in invasive lobular carcinomas than in invasive ductal carcinomas, although this difference was of borderline significant (P = 0.084). Cases in the present series were also immunostained for cerB-2 protein overexpression. A significant association between p53 protein accumulation and cerbB-2 protein overexpression was seen (P = 0.036). The results of the present study indicate that p53 protein may play a role in regulation of E-cadherin protein expression.

Prospective randomized study of routine intraoperative cholangiography during open cholecystectomy: long-term follow-up and multivariate analysis of predictors of choledocholithiasis.

A prospective randomized study was performed to assess the value of routine intraoperative cholangiography (IOC) during cholecystectomy for gallstone disease. Four hundred and fifty-seven consecutive patients were screened for the presence of 11 predefined clinical criteria assumed to indicate choledocholithiasis. Two hundred and eighty patients who had no positive criteria and in whom preoperative endoscopic retrograde cholangiography had not been performed were randomized at the operating table to the IOC or no-IOC group. Follow-up was performed 6 to 8 years after the operation with a questionnaire and by use of clinical, biochemical, and radiologic investigations as indicated. Multivariate analysis was used to identify independent predictors of choledocholithiasis and the combination of criteria having the best predictive ability. The frequency of common bile duct calculi at operation was significantly correlated with age and with all clinical criteria except recent or present pancreatitis. However, only serum bilirubin level, cystic duct diameter, demonstration of common bile duct calculi on preoperative imaging or intraoperative palpation, and age at operation were independent predictors of choledocholithiasis. The overall best subset of clinical indicators contained all criteria with the exception of pancreatitis and alkaline phosphatase level. Negative predictive ability of the set of criteria was 100% for patients up to 60 years of age and 97% for patients older than 60 years at the time of operation. No case of residual common bile duct calculi was present in the IOC and no-IOC groups at follow-up. Our data strongly support a policy of performing IOC during cholecystectomy only when clinical criteria suggest the presence of common bile duct abnormalities or to clarify ductal anatomy.

Screening for breast cancer is associated with a low degree of psychological distress.

Psychological distress was measured among women on the day of recall after mammography in an official screening programme, and 4 weeks after the diagnosis was given. The Hospital Anxiety and Depression Scale (HADS) and a questionnaire to assess reactions to the examination were completed by 213 (97%) women aged 50-69 years. Among those without cancer, there were 45 (24.3%) who were anxiety cases and eight (4.3%) depression cases (HADS) on the day of recall mammography and 12 (7.3%) and three (1.8%) respectively after 4 weeks (P<0.001). Among those with cancer, the corresponding figures were seven (28.0%) and one (4.8%) before and six (24.0%) and three (12%) after screening (n.s.). A total of 194 (97%) women were definitely satisfied with the screening programme, and 195 (98%) would recommend others to participate. In conclusion, recall after mammography is associated with transiently increased levels of anxiety and depression in women without cancer. For those with cancer, the psychological distress continues. The women were almost unanimously content with participating in the screening programme.

Micrometastasis to axillary lymph nodes and bone marrow in breast cancer patients.

The axillary lymph nodes of 100 lymph node-negative breast cancer patients with known bone marrow status have been re-examined to explore the presence of micrometastasis in lymph nodes and the covariance of micrometastasis to bone marrow and lymph nodes. Nodes were serially sectioned at three intervals of 100 microm, followed by immunohistological (two sections) and haematoxylin-eosin staining (one section). Tumours were mainly T1 and T2, and the patients had on average 13 (4-22) lymph nodes removed. In two patients, micrometastasis was detected in one node. Another 25 patients possessed single positive immunostained cells mimicking tumour cells. These cells have been shown to be false positive cells by Perl and melanin staining. One patient had metastasis to several nodes missed by the original examination. Immunocytochemical detection of micrometastasis in bone marrow revealed 11 marrow-positive patients. This study has identified a low frequency of micrometastasis to lymph nodes, and no covariance with micrometastasis in the bone marrow was seen. Bone marrow micrometastasis may be an independent prognostic variable, separate from axillary node status.

Do women newly diagnosed with breast cancer and consulting surgeon assess decision-making equally?

This study assesses the perception of the decision-making process of 25 surgeons and 194 patients (aged 21-81 years) who had newly diagnosed breast cancer and had to undergo mastectomy or breast-conserving surgery (BCS). The majority of women wanted to participate in decision-making. When it was medically possible to give a choice between BCS and mastectomy, only 59% of women received a choice. The main reason that 11% of the women went against surgeon's recommendations was fear of cancer recurrence. The most influential factors for women were the surgeon's recommendation, and fear of cancer recurrence. Medical assessment and the cosmetic result were the most influential factors for the surgeons. Female surgeons were more influenced by their assessment of the women's need for security, than male. In conclusion, not all women who are eligible for BCS receive an option. Women and surgeons emphasize influencing factors differently. The surgeon's gender was found to influence recommendation given.

Immunoreactive glucagon and insulin C-peptide in man after resection of the pancreas and total pancreatectomy.

Pancreatic-type glucagon (PTG) has been found in the plasma of totally pancreatectomized human beings. Arginine infusion, however, caused no increase in PTG. Pancreas-resected patients had a normal response of PTG to arginine and a subnormal increase in C peptide. Gut glucagon-like immunoreactants (gut GLI) were increased in resected patients and further increased in totally pancreatectomized patients. Gut GLI showed no change during arginine stimulation.

Transhepatic endoprosthesis and surgical anastomosis in the palliative treatment of bile duct obstructions.

Ninety-six patients with non-resectable malignant tumours occluding the bile duct were treated either with a transhepatic endoprosthesis (n = 60) or a surgical biliointestinal anastomosis (n = 36). The mean survival time for patients treated with a transhepatic endoprosthesis was 5.8 months, as compared with 8,1 months for patients treated surgically. The mortality rates in the first 30 days were 18% and 17% for patients treated anastomosis, respectively. We consider that this militates in favour of an endoprosthesis rather than surgery.

Logistics of referral, diagnostic assessment and treatment of patients with breast symptoms and signs.

BACKGROUND AND AIMS: The logistics of diagnosis and treatment in a hospital with slightly above 400 new cases of breast cancer per year is analysed. MATERIALS AND METHODS: The patient flow from referral, through the diagnostic procedures and through surgical treatment is described. RESULTS AND CONCLUSIONS: The basic principle of the diagnostic assessment is the triple diagnostic procedure including mammography supplemented by ultrasonography, fine needle aspiration cytology and clinical examination. The radiologist and pathologist are working together in the breast diagnostic centre and are thus able to give a "single visit diagnosis" in most cases. The surgeon sees the patient either the same day or the next. A "consensus meeting" held each week with representatives for all specialities present has an important function in quality assurance and education. If one or more of the triple diagnostic components reach conclusion level "suspicious lesion", surgery is indicated. In hospital management is based on day surgery for all biopsies, wide excisions with or without sentinel node and some ablatio simplex mammae. For wide excision and ablation with complete axillary node clearance, the patients are transferred from the day surgery unit to a patient hotel after 3-4 hours of observation and stay till the drain can be removed. Only in rare case of high cardiopulmonary risk, beds in ordinary wards are used. This is a highly cost efficient logistic saving the hospital approximately 400,000 EUR a year compared to ordinary in hospital treatment.

A microcomputer-based structured journal system for diseases of the female mammary gland.

A medical journal system for female patients with diseases of the mammary gland is described. The system is developed in a commercial database system, and is run by microcomputer. The system has been used for almost 3 years in a department with approximately 550 new patients referred per year. Experience from daily use in patient care, and as a tool for retrieval of medical and administrative data, is reported. Further development of the system is discussed.

[Psychological, social and economic situation of women surgically treated for cancer]. / Kreftopererte kvinners psykiske, sosiale og økonomiske forhold.

INTRODUCTION: As part of an international effort, a study of the psychosocial condition of women with cancer in Norway was performed in 1997. MATERIAL AND METHODS: 851 women with breast or gynaecological cancer in 27 Norwegian hospitals were asked to fill in a multi-choice questionnaire. RESULTS: 76% of the breast cancers were detected by the women themselves, 19% by mammography and 11% by clinical examination. Similar numbers for gynaecological cancer were 59% by the women and 41% by the doctors (13% screening smear). 25% of the women were informed about the cancer diagnosis by telephone and 9% by letter. 87% were satisfied with treatment and care, 7% dissatisfied. 62% were satisfied with the availability of doctors, 20% not. In 47% of the breast cases, therapy alternatives were discussed with the patients. In 23% of gynaecological, 50% of breast, and 72% of gynaecological cancer, patients had no wish to participate in the decision. 94 of a total of 850 patients (11%) experienced financial problems after the diagnosis had been established. More than 90% of the women had a better or unchanged relation to their partner, family and friends after treatment. However, 30% of the breast and 14% of the gynaecological cancer patients had problems with their body image, and 16% and 15% felt they were less sexually attractive. 89% felt their partner coped well with the situation, 9% had problems and only 2% lost their partner. 32% of the patients had used alternative medicine, 44% of those with recurrence and 28% under primary treatment. INTERPRETATION: Women operated for breast and gynaecological cancer face a variety of psychosocial and financial problems.

[Microductectomy. A simple method for excision of intraductal changes in the breast]. / Mikroduktektomi. Enkel metode for eksisjon av intraduktale forandringer i mamma.

Next to tumour and pain, discharge from the nipples is the most common reason for remitting women to a breast clinic, and comprises 3-6% of the total cause of remittance. We describe a technique for localizing a duct system, where a defect is found by galactography by injection of methylenblue/Isopaque Amin 1:1 in the duct system prior to operation. Ultrasonography can be used to localize the ectatic ducts in cases where there is no secretion on the day of the scheduled operation. The blue colour enables the surgeon to excise the defect duct very precisely. Such a microductectomy preserves breast tissue and gives a better cosmetic result than with complete central ductectomy. We discuss examination and treatment of women with discharge from the nipple.

[Breast cancer surgery in Norway 1990-95 illustrated by data from SINTEF United]. / Brystkreftkirurgi i Norge 1990-95 belyst med data fra SINTEF Unimed.

BACKGROUND: Breast-conserving therapy has been shown to be as effective as mastectomy in many cases; hence in many countries more breast cancer patients are offered this type of treatment. This study focuses on the amount and type of surgery used in Norway for breast cancer patients and the possible use of hospital discharge data to evaluate the diffusion of this surgical practice. MATERIAL AND METHODS: Data from the nationwide Register of Hospital Discharges in Norway at SINTEF Unimed for patients operated for breast cancer from 1990 to 1995 were used. RESULTS: 11,041 patients were registered with 11,727 hospital admissions for breast cancer operations from a total of 64 hospitals. The discrepancy in the number of breast cancer patients with the National Cancer Registry was 7%. Breast-conserving surgery was performed in 19.7%. An increase from 17% in 1990 to 21% in 1995 was found, but with variations according to type of hospital, county and age of patients. INTERPRETATION: The percentage of breast conserving surgery is still low in Norway; this indicates that many women are not offered this type of surgery. With some caution, the data from SINTEF Unimed can be used to reflect the clinical practice over time at Norwegian hospitals. Further improvements could be obtained if national identity numbers were added to the database.

[Follow-up of women surgically treated for breast cancer]. / Etterkontroll av kvinner operert for cancer mammae.

From May 1997, all breast cancer patients who had undergone ablatio were asked to contact their general practitioner for follow-up after six months. Evaluation of the method used was performed by means of a questionnaire sent to 148 women. At the same time report forms returned from the general practitioners were registered. 132 women returned the questionnaires (89%). Only seven women (5%) had not contacted their general practitioner. 117 women (89%) had been or were summoned to their general practitioner. This shows that general practitioners take responsibility for follow-up when the women get in touch. We received 52 (58%) report forms from the general practitioners. The reason for this low response rate among the general practitioners might be inadequate motivation.

[Content, function and structure of standardized hospital waiting lists in Norway]. / Innhold, funksjon og oppbygging ved standardiserte sykehusventelister i Norge.

Standardization of hospital waiting lists will improve the quality of information on waiting lists, allowing comparison between different hospitals and different counties, and a nationwide aggregation. Waiting lists must include all elective referrals, and will accordingly allow future planning and surveillance of the complete elective hospital activity. A current indication for evaluation/treatment in hospital is a prerequisite for waiting list registration. The registers must be continuously validated by erasing old referrals. Referrals are categorized in relation to hospital departments, sections and levels of care. Subgroups comprise medical specialties and diagnostic groups.

[Grouping and calculated measurements of standardized waiting lists in Norway. Definitions and interpretations of waiting lists]. / Gruppering og opptellingsmåter ved standardiserte ventelister i Norge. Definisjoner og tolkning av ventetider.

Waiting list parameters calculated for defined dates and time periods allow studies to determine balance between new and completed referrals. The authors discuss various sub-groupings of the waiting lists. The main waiting time parameter is mean waiting time for the various levels of care in the case of the different medical specialties and diagnostic groups. Waiting time is defined as the difference between date of first admission to hospital and the date when the patient was referred. It is possible to calculate total waiting time for patients undergoing out-patient evaluation before in-patient or day-care treatment. Aggregated waiting times should exclude control admissions and admissions postponed at the wish of the patient.