Consistency of patient- and doctor-assessed cosmetic outcome after conservative treatment of breast cancer

The cosmetic results of the breast (144 patients)were analysed after segmental resection and axillary dissectionwith or without postoperative radiotherapy for early low-riskbreast cancers. Cosmetic results were assessed over time(3, 9, 18, 36, 48 months respectively) bythe patient and by the physician. Patients ratedthe overall cosmetic result good or excellent in92% of cases after 3 months. The proportionof good or excellent cosmetic results decreased overtime and after four years 89% of patientsclassified themselves in this category, whereas the physicianassessed the outcome as good or excellent in91% of cases after 3 months and 75%after 4 years. The inter-observer consistency between physicianand patient in assessing the cosmetic outcome was=0.42 at the beginning and decreasedover time (=0.07 after 4 years).The intra-observer variation over time was =0.53 for the patient and =0.32for the physician.Inter-observer consistency between patient and physician was moderateimmediately following treatment but decreased over time. Thefeeling of satisfaction of the patient was relativelystable whereas the opinion of the physician becamesomewhat more critical over time. Therefore the intra-observerconsistency over time was somewhat better for thepatient than for the physician.     

Interlaboratory comparison of HER-2 oncogene amplification as detected by chromogenic and fluorescence in situ hybridization.

PURPOSE: Chromogenic in situ hybridization (CISH) is a new modification of the fluorescence in situ hybridization (FISH) technique for detection of oncogene amplification in archival tumor samples. In CISH, the oncogene probe is detected using a peroxidase reaction, allowing use of transmitted light microscopy. We compared detection of HER-2/neu amplification by CISH with a Food and Drug Administration-approved two-color FISH test in an interlaboratory setting. EXPERIMENTAL DESIGN: Formalin-fixed paraffin-embedded tumor samples from 197 breast cancers were analyzed for HER-2 amplification by CISH. Two-color FISH (PathVysion) CISH of 17 centromere was done if the observer considered it necessary to ascertain amplification status in tumors with borderline HER-2 CISH copy numbers. RESULTS: Paired CISH/FISH results were available from 192 (97%) of 197 cases, no clear difference in success rates of either method was observed. Centromere 17 CISH was considered necessary in seven tumors. CISH and two-color FISH results were concordant in 180 cases (93.8%). There were 92 and 88 tumors found HER-2 amplified and nonamplified, respectively, by both methods. Eight tumors were amplified by CISH but not by FISH, and four tumors exhibited the opposite condition (kappa coefficient 0.875). In 7 of 12 cases differences between the two methods could have related to a lack of CISH chromosome 17 information. The remaining cases were explained by difficult histology (ductal carcinoma in situ, poor representativity, dense lymphocytic infiltration, or intratumoral heterogeneity). CONCLUSIONS: These results indicate that CISH could provide an accurate and practical alternative to FISH for clinical diagnosis of HER-2/neu oncogene amplification in archival formalin-fixed breast cancer samples.     

Pre-operative serum level of tumour-associated trypsin inhibitor and residual turnour size as prognostic indicators in Stage III epithelial ovarian cancer

Objective To evaluate the use of the pre-operative tumour-associated trypsin inhibitor (TATI) level and residual tumour size at primary surgery as a prognostic indicators for patients with Stage III epithelial ovarian cancer.
Design Retrospective cohort study.
Setting Department of Obstetrics and Gynaecology, University Hospital, Helsinki, Finland.
Participants Ninety-eight women with Stage III ovarian cancer.
Methods TATI was measured by radioimmunoassay from serum samples obtained within one week before surgery. A cutoff value of 22 μg/L was used. Multivariate analysis included pre-operative TATI level, age, histologic grade and histologic type. Mantel-Cox test was used for calculating statistical significance of differences in survival between groups.
Main outcome measures Cumulative five-year survival, pre-operative serum TATI level and residual tumour size.
Results Surgery was optimal (residual tumour size ≤ 2 cm) in 55 patients and suboptimal (residual tumour size > 2 cm) in 43. Pre-operative TATI level ≤ 22 μg/L predicted better prognosis both in patients with optimal and suboptimal surgery compared with patients with pre-operative TATI level > 22 μ/L. Patients with optimal surgery and a pre-operative TATI > 22 μg/L had a twofold relative risk of death compared with those with a pre-operative TATI ≤ 22 μg/L. The cumulative survival was less than three years for patients with suboptimal surgery and pre-operative TATI > 22 μg/L.
Conclusions Pre-operative serum TATI in combination with residual tumour size may be useful in stratifying patients with Stage III ovarian cancer into different categories in randomised treatment trials.     

Results of metal-on-metal hip resurfacing in patients 40 years old and younger

The prevalence of total hip arthroplasty in young patients is small but increasing. We analyzed the results of metal-on-metal hip resurfacing (MMHR) in patients aged 40 years or less. In total 74 operations were performed on 64 patients. Mean age at operation was 33.2 years. HHS averaged 92.3 points at latest follow-up, mean UCLA activity was 8.2. Patients with comorbidity evinced lower scores in HHS, in UCLA activity and in quality of life than patients without comorbidities. Eight revisions (10.8 %) were performed, of which seven due to adverse reaction to metal debris. Seven-year survival was 90.5 %. The functional outcome of hip resurfacing in this cohort was excellent, but overall survival was unsatisfactory. Further analysis is required to verify the role of hip resurfacing among young and active patients.     

Preconception metabolic indicators predict gestational diabetes and offspring birthweight

Pregnancy conditions such as gestational diabetes (GDM) and macrosomia lead to an increased risk of diabetes and cardiovascular disease in the offspring, perpetuating a cycle of poor health. We hypothesized that (1) pre-pregnancy indicators of metabolism would be associated with GDM and birthweight; and (2) the lipid accumulation product (LAP; incorporating waist circumference and triglycerides) and visceral adiposity index (VAI; incorporating waist circumference, triglycerides, and HDL-c) would be better predictors of GDM and birthweight than other indicators. Data from the Cardiovascular Risk in Young Finns Study were linked to the Finnish birth registry for 349 women. BMI, triglycerides, waist circumference, insulin, HOMA-IR, LAP, and VAI at the visit prior to the pregnancy were examined as predictors of GDM and large-for-gestational-age (LGA) using logistic regression with adjustment for age, parity, and smoking. Waist circumference was the strongest predictor of GDM (adjusted odds ratio [aOR] 1.66, 95% confidence interval 1.16–2.38) and LGA (aOR 1.41, 1.00–1.99). For GDM, all markers had similar discrimination; for LGA, the area under the receiver operating curve for waist circumference was significantly higher than for BMI (p?相似文献   

WOUND CLOSURE BY DERMATOTRACTION AFTER FASCIOTOMY FOR ACUTE COMPARTMENT SYNDROME

Intramuscular pressure (IMP) was measured in 16 patients during secondary wound closure by dermatotraction with external tissue extension (ETE®). Secondary wound closure was done 4-16 days after fasciotomy for acute compartment syndrome. The traction between wound edges was 2.5 N in the first six patients and 3.5 N in the following 10 patients. Mean (SD) IMP was 6.9 (3.5) mmHg before wound closure. It increased to 12.3 (1.4) mmHg in the 2.5 N group and to 24.7 (7.0) mmHg in the 3.5 N group when dermatotraction was applied. Mean (SD) leg perfusion pressure in the 2.5 N group decreased by 7% to 69.3 (10.9) mmHg and in the 3.5 N group by 23% to 62.2 (7.4) mmHg. None of the patients needed a skin graft. We conclude that dermatotraction by ETE® raises IMP intraoperatively sufficiently to preserve adequate limb perfusion pressures.     

Trastuzumab emtansine: mechanisms of action and drug resistance

Trastuzumab emtansine (T-DM1) is an antibody-drug conjugate that is effective and generally well tolerated when administered as a single agent to treat advanced breast cancer. Efficacy has now been demonstrated in randomized trials as first line, second line, and later than the second line treatment of advanced breast cancer. T-DM1 is currently being evaluated as adjuvant treatment for early breast cancer. It has several mechanisms of action consisting of the anti-tumor effects of trastuzumab and those of DM1, a cytotoxic anti-microtubule agent released within the target cells upon degradation of the human epidermal growth factor receptor-2 (HER2)-T-DM1 complex in lysosomes. The cytotoxic effect of T-DM1 likely varies depending on the intracellular concentration of DM1 accumulated in cancer cells, high intracellular levels resulting in rapid apoptosis, somewhat lower levels in impaired cellular trafficking and mitotic catastrophe, while the lowest levels lead to poor response to T-DM1. Primary resistance of HER2-positive metastatic breast cancer to T-DM1 appears to be relatively infrequent, but most patients treated with T-DM1 develop acquired drug resistance. The mechanisms of resistance are incompletely understood, but mechanisms limiting the binding of trastuzumab to cancer cells may be involved. The cytotoxic effect of T-DM1 may be impaired by inefficient internalization or enhanced recycling of the HER2-T-DM1 complex in cancer cells, or impaired lysosomal degradation of trastuzumab or intracellular trafficking of HER2. The effect of T-DM1 may also be compromised by multidrug resistance proteins that pump DM1 out of cancer cells. In this review we discuss the mechanism of action of T-DM1 and the key clinical results obtained with it, the combinations of T-DM1 with other cytotoxic agents and anti-HER drugs, and the potential resistance mechanisms and the strategies to overcome resistance to T-DM1.