Ten-year follow-up of skin-sparing mastectomy followed by immediate breast reconstruction.

BACKGROUND: The oncological safety of skin-sparing mastectomy (SSM) followed by immediate breast reconstruction (IBR) is debated owing to a presumed compromise in the completeness of mastectomy. Current evidence is poor as it is based mostly on short-term follow-up data from highly selected patients. METHODS: A prospectively maintained institutional database was searched to identify patients who underwent SSM and IBR between 1995 and 2000. A retrospective review of medical records was carried out, including only patients with ductal carcinoma in situ and invasive breast cancer. During this time all patients treated with mastectomy were offered IBR regardless of tumour stage. RESULTS: Follow-up data from 253 consecutive patients with IBR were reviewed. Patients with incomplete follow-up data and those undergoing SSM for recurrent disease following previous lumpectomy were disregarded, leaving 207 for analysis. Offering IBR to all women requiring mastectomy resulted in a large proportion of patients with advanced disease. During a median follow-up of 119 months, 17 (8·2 per cent) locoregional, six (2·9 per cent) local and 22 (10·6 per cent) distant recurrences were detected; the overall recurrence rate was 39 (18·8 per cent). Overall recurrence rate was associated with axillary lymph node metastasis (P = 0·009), higher stage (P < 0·001) and higher tumour grade (P = 0·031). The breast cancer-specific survival rate was 90·8 per cent (19 of 207 women died from recurrence). CONCLUSION: Based on these long-term follow-up data, SSM combined with IBR is an oncologically safe treatment option regardless of tumour stage.

Impact of national guidelines on family history breast cancer surveillance.

The breast cancer risk of women already under family history surveillance was accurately assessed according to national guidelines in an attempt to rationalize the service. Women attending two breast units in Glasgow between November 2003 and February 2005 were included. One thousand and five women under annual surveillance were assessed and had their relatives diagnoses verified. Four hundred and ninety-seven women were at significantly increased risk and eligible for follow-up. Five hundred and eight (50%) women attending were not eligible for family history surveillance, and 498 (98%) of these women accepted discharge. In conclusion, national guidelines have helped to more clearly define women who should undergo surveillance. This avoids unnecessary and potentially harmful routine investigations, and the service has been improved.

Glycoproteomic profiling of serum peptides in canine lymphoma and transitional cell carcinoma.

Differential expression of fucosylated glycoproteins has been correlated with malignancy and metastatic potential in various types of neoplasia. Utilizing glycoproteomics techniques, changes in fucosylated serum peptides associated with naturally occurring canine lymphoma and transitional cell carcinoma (TCC) have been evaluated. In both types of neoplasia, the majority of the fucosylated peptides that changed increased with the cancer. In one lymphoma case that was examined over the course of the disease, the same fucosylated peptides that increased during pre-chemotherapy decreased during post-chemotherapy, and then subsequently increased upon recurrence of the lymphoma. When comparing all the fucosylated peptides that increased in both types of cancer, there were only two peptides in common allowing discrimination between lymphoma and TCC based on their peptide profiles. These results emphasize the prospect of glycopeptide profiling in proteomics for use in discovering a panel of non-invasive, diagnostic or prognostic biomarkers of cancer.

Immediate breast reconstruction does not lead to a delay in the delivery of adjuvant chemotherapy.

Immediate breast reconstruction (IBR) has been considered by some to lead to a delay in the delivery of adjuvant chemotherapy. Our aim was to determine whether IBR led to a delay when compared to conservation surgery and non-reconstructive mastectomy. Ninety-five cases of IBR receiving chemotherapy were reviewed. These were compared to 95 consecutively treated patients undergoing conservation surgery and 95 undergoing non-reconstructive mastectomy. Our data shows that IBR does not lead to a delay in the delivery of adjuvant chemotherapy when compared to standard non-reconstructive surgery and should not adversely affect breast cancer outcome.

Calcitonin gene-related peptide is not essential for the development of pressure overload-induced hypertrophy in vivo.

The regulatory neuropeptide calcitonin-gene related peptide (CGRP) has been shown to evoke a hypertrophic response in isolated cardiomyocytes in vitro, an effect which was attributed to PKC activation. Activation of PKC has previously been implicated in the development of cardiac hypertrophy. We therefore investigated the role of CGRP in pressure overload-induced hypertrophy in vivo, which has not previously been reported. Constriction of the ascending aorta of rats resulted in an increase in the heart weight to body weight ratio, increased myocyte diameter, re-expression of the fetal genes ANF, MHCbeta and skeletal alpha-actin, and decreased expression of the adult genes GLUT4 and SERCA2a. Treatment of neonatal rat pups (1-2 days old) with capsaicin (50 mg/kg), resulted in the permanent de-afferentation of small-diameter unmyelinated CGRP-containing sensory C-fibres. Such treatment caused a 68% decrease in the CGRP-like immunoreactivity of hearts isolated from 10 week old rats (p < 0.001). Contrary to expectations, aortic constriction of capsaicin treated rats had no effect on the development of hypertrophy at the trophic, morphometric or gene expression levels. The results suggest that the development of pressure overload-induced hypertrophy in vivo does not require the regulatory neuropeptide CGRP.

Expression of Ku70 correlates with survival in carcinoma of the cervix.

Cervical carcinoma affects around 3400 women in the UK each year and advanced disease is routinely treated with radiation. As part of a programme to establish rapid and convenient methods of predicting tumour and patient responses to radiotherapy, we have examined the relationship between the pre-treatment expression of the Ku components of the DNA damage recognition complex DNA-PK and patient survival in cervical carcinoma. Using immunohistochemistry of formalin-fixed sections of tumour biopsies, antibodies to Ku70 and Ku80 stained identical regions of tumour and there was a high degree of correlation between the mean number of cells stained positive for the two components in 77 tumours (r = 0.82, P<0.001). In 53 tumours there was a borderline significant correlation between measurements of tumour radiosensitivity (surviving fraction at 2 gray: SF2) and Ku70 expression (r = 0.26, P = 0.057) and no correlation for Ku80 (r = 0.18, P = 0.19). However, all tumours with a low number of Ku70 or Ku80 positive cells were radiosensitive. Furthermore, using log-rank analysis there was significantly higher survival in the patients whose tumours had a low Ku70 expression (P = 0.046). This difference was also reflected with Ku80, but did not reach statistical significance (P = 0.087). The study suggests that lack of Ku protein leads to radiosensitivity in some tumours and that other factors are responsible for radiosensitive tumours with high Ku expression. It is likely that the most accurate prediction of treatment outcome will lie in assessing the expression of several proteins involved in the recognition and repair of DNA damage, one of which will be Ku.

Mammalian recombination-repair genes XRCC2 and XRCC3 promote correct chromosome segregation.

Growth and development are dependent on the faithful duplication of cells. Duplication requires accurate genome replication, the repair of any DNA damage, and the precise segregation of chromosomes at mitosis; molecular checkpoints ensure the proper progression and fidelity of each stage. Loss of any of these highly conserved functions may result in genetic instability and proneness to cancer. Here we show that highly significant increases in chromosome missegregation occur in cell lines lacking the RAD51-like genes XRCC2 and XRCC3. This increased missegregation is associated with fragmentation of the centrosome, a component of the mitotic spindle, and not with loss of the spindle checkpoint. Our results show that unresolved DNA damage triggers this instability, and that XRCC2 and XRCC3 are potential tumour-suppressor genes in mammals.

Multiphase hepatic CT with a multirow detector CT scanner.

OBJECTIVE: The aim of this study was to evaluate a new injection-acquisition technique performed using a multirow detector CT scanner for separation of three distinct hepatic circulatory phases (hepatic artery, portal venous inflow, hepatic venous) and to determine which of these phases is optimal for detecting hypervascular neoplasm. MATERIALS AND METHODS: Two sequential acquisitions were performed during a single breath-hold followed by a third acquisition beginning 60 sec after injection. Injection-to-scan delay for the first acquisition was the individual patient's circulation time, which was determined by a preliminary mini bolus. The mean attenuation of the upper abdominal aorta, portal vein, and hepatic parenchyma were determined for each imaging pass in 20 patients with cirrhosis and 20 patients without cirrhosis. Tumor-to-liver contrast for hypervascular primary and metastatic neoplasm was evaluated in a different set of 16 cirrhotic patients and nine noncirrhotic patients. Three-dimensional CT arteriograms were obtained from first-pass data. RESULTS: Three distinct circulatory phases (hepatic artery, portal vein inflow or late arterial, and hepatic venous) were seen in cirrhotic and noncirrhotic patients. Maximum tumor-to-liver contrast for hypervascular primary and metastatic neoplasm occurred during the second pass for both cirrhotic (p < 0.006) and noncirrhotic (p < 0. 001) patients. A three-dimensional hepatic-mesenteric CT arteriogram of normal or anomalous hepatic vessels without venous overlay was obtained from first-pass data in all patients. CONCLUSION: Rapid-sequence hepatic helical CT allows selection of the optimal time interval for hypervascular tumor detection. A new paradigm for rapid hepatic CT acquisition-namely, hepatic arterial, portal vein inflow, and hepatic venous phases-is recommended to replace hepatic artery dominant and portal venous phases.

Evaluating the effectiveness of 2 educational interventions in family practice.

BACKGROUND: Structured feedback of information can produce change in physician behaviour. The objective of this study was to assess the effectiveness of 2 educational interventions for improving the quality of care provided by family physicians in Ontario: the Practice Assessment Report (PAR) and the Continuing Medical Education Plan (CMEP) with a follow-up visit by a mentor. METHODS: The study was a randomized controlled trial. Physicians in the control group received only the PAR, whereas those in the experimental group received the PAR, CMEP and mentor interventions. The participants were 56 family physicians and general practitioners (27 in the PAR group and 29 in the CMEP group) in southern Ontario who agreed to participate in the interventions and provide data. A total of 2395 patients randomly sampled from the practices returned questionnaires and consented to have their medical records abstracted. The outcome measures were global scores in 4 areas--quality of care, charting, prevention and overall use of medications--and patient ratings of satisfaction with care and preventive practices. The measures were applied at the beginning (phase 1) and end (phase 2) of the study. RESULTS: The mean global scores at the end of the study for the PAR group were 70.1% for quality of care, 84.7% for prevention, 77.7% for charting and 82.2% for overall use of medications. The corresponding scores for the CMEP group were 68.3%, 82.1%, 76.4% and 83.2%. In the patient satisfaction component, the personal care scores at phase 2 were 93.6% for the PAR group and 94.6% for the CMEP group. Examples of the scores for prevention for the PAR group were 98.3% for children's current immunization, 96.6% for blood pressure measured within the previous 5 years, 79.4% for referral of women of the appropriate age for mammography within the previous 2 years, and 58.4% for discussion about alcohol use. The corresponding scores for the CMEP group were 95.8%, 97.6%, 77.6% and 64.6%. The changes in mean scores between phase 1 and phase 2 ranged from -1.9 to 2.3 points. There were no significant differences between the 2 groups in phase 1 or phase 2 scores or in change in scores. A total of 64.3% of the physicians rated the PAR as useful, 26.5% found the CMEP to be useful, and 41.0% considered the mentor strategy to be a useful form of continuing medical education. Although changes in practice related to the PAR, CMEP or mentor were reported by some physicians, they were not related to chart audit or patient scores. INTERPRETATION: Educational interventions based on quality-of-care assessments and directed to global improvements in quality of care did not result in improvements in the outcome measures. Educational interventions may have to be targeted to specific areas of the practice, with physicians being monitored and receiving ongoing feedback on their performance.

Unusual ligand binding at the active site domain of an engineered mutant of subtilisin BL.

As an attempt to recruit the third calcium binding site of thermitase into subtilisin BL, a Bacillus lentus alkaline protease (BLAP), the amino acid sequence from position 50 to 60 and position 92 was modified to the equivalent amino acids in thermitase. The resulting protein, designated BLAPm109, exhibited unusual biochemical features. Peptide mapping and gel electrophoresis revealed that two protein species co-purify in a ratio of about 1:1. Form 1 consisted of a single polypeptide of 269 amino acid residues. Form 2 was the same protein but with an internal peptide bond cleavage at the C-terminus of position 54. On electropherograms a dimer of Form 1 and Form 2 was also detectable. A zymogram showed that all three molecular species were catalytically active. From this protein mixture, crystals suitable for X-ray analysis were nevertheless obtained. SDS-PAGE of protein recovered from a crystal revealed that only Form 2 appears. in the crystal. The space group for this crystal was P21 with unit cell dimensions of a=42 angstroms, b=58 angstroms, c=47 angstroms and beta = 106.3 degrees. Examination of the preliminary electron density map revealed that the "thermitase loop" from 50 to 60 departs from the surface of the protein and winds through the active site of a symmetry-related copy of the asymmetric unit.

Observations on nursing home residents with a history of hip fracture.

The authors evaluated nursing home residents with a prior history of hip fracture for osteopenia and its risk factors, and attempted to learn to what extent the residents' bone status had been considered by their primary care physicians. Thirty-one hip fracture residents in the Milwaukee VA nursing home were studied to determine their status with regard to bone mineral density of the proximal femur, and the following risk factors or predictors of osteopenia: history of smoking; history of fractures; calcium and vitamin D intake; underweight; immobility; hypogonadism; and administration of drugs that may accelerate bone demineralization. Data were also collected on the evaluation and management of the post hip fracture residents in three other nursing homes. In the Milwaukee nursing home, out of 31 hip fracture survivors, 74% had sustained a hip fracture before admission to the nursing home; 29% had a history of second fracture. In 84% of patients, there was no mention of osteopenia in the active medical problem list and, therefore, there was no intervention plan in place to improve or prevent further bone loss. Thirty-two percent were underweight, 36% were currently smoking, 55% were immobile, 64% were consuming at least one medication that might increase bone loss, calcium intake was less than 1,000 mg daily in 52%, and 66% were hypogonadal (serum testosterone level less than 300 ng/dL). Chart reviews of the hip fracture survivors at three other nursing homes revealed similar findings. Approximately 5-15% of nursing home residents are hip fracture survivors. They usually have severe osteopenia and multiple risk factors for further bone loss and future fractures.(ABSTRACT TRUNCATED AT 250 WORDS)

Iodine-131 contamination from thyroid cancer patients.

High-dose radioactive iodine therapy using 131I is the treatment of choice for patients with thyroid cancer following thyroidectomy. Because of the large amount of activity which is excreted during hospitalization, contamination hazard from 131I excretion via perspiration, saliva, breath and urine may arise. In eight patients treated with doses of 131I ranging from 3.7 to 14.8 GBq (100-400 mCi), activity levels were measured in room air, from room surfaces, the toilet, the patients' exhaled breath, skin, saliva and toothbrushes, and the gloves used by medical staff. Thyroid bioassays were also performed on medical staff personnel caring for these patients both before and two days after administration of the treatment dose. Removable activity from the skin was positively correlated with treatment dose and reached a maximum at 24 hr post-therapy. Removable activity from room surfaces exceeded the level of contamination which requires clean-up in a restricted area during the patient's hospitalization. Thyroid bioassays on medical staff showed no significant uptake 2 days after treatment. The relatively high activities present in the saliva, urine and on the skin of these patients emphasizes the need for all individuals coming in contact with these patients to be made aware of the contamination hazard present.

Pseudotumor of the craniovertebral junction associated with chronic subluxation: MR imaging studies.

Masses at the craniovertebral junction generally have serious prognostic implications. However, the authors studied three patients who had chronic atlantoaxial subluxation from either degenerative disease or congenital dysplasia of the dens and who also had benign fibrous masses in this region, confirmed at surgery. The association of masses of the craniovertebral junction with chronic atlantoaxial subluxation raises the possibility that the underlying cause of the masses is chronic mechanical irritation. All patients were imaged with metrizamide myelography and adjunctive computed tomography (CT), then by magnetic resonance (MR) imaging. MR images were not only superior to myelograms and CT scans in delineating the exact extent of the lesions, they also indicated the benign, fibrous nature of the masses.

The effect of varying spatial resolution on the detectability of diffuse pulmonary nodules. Assessment with digitized conventional radiographs.

Detection and discrimination of miliary disease and small pulmonary nodules were tested at six levels of spatial resolution varying between 0.3 and 2.5 l.p./mm, and receiver operating characteristic (ROC) curves were generated. The test images were obtained by digitizing selected normal and abnormal standard film/screen radiographs. Although there was no statistically significant difference in observer performance between 0.5 and 2.5 l.p./mm, the findings may have clinical relevance. Further observer detection studies of different disease processes are planned to help formulate performance standards for an electric digital radiographic device for chest imaging.