Mikael Railo

The prognostic value of insulin-like growth factor-I in breast cancer patients. Results of a follow-up study on 126 patients

The insulin-like growth factor-I is an important mitogen and has a growth promoting property, especially in breast cancer. This work analyses the prognostic value of the insulin-like growth factor receptor-I (IGFR-I), which belongs to the group of membrane receptors for growth factors. The study included 126 patients. 49 patients (39%) were IGFR positive (> or = 4.0%). There was a significant correlation between IGFR and oestrogen receptor (ER) status (P = 0.001), but not between IGFR and progesterone receptor status (PR; P = 0.07). There was no correlation between node status and IGFR. The expression of IGFR had a strong significance in the disease-free analysis (P = 0.0108). The IGFR status was not of predictive value in the node-negative subgroup (64 patients). Within the ER-negative group, the disease-free analysis further stratified with IGFR revealed that patients with IGFR-positive and ER-negative cancers are in a worse situation than IGFR-negative ER-negative cancer patients (P = 0.01).

Prognostic value of Ki-67 immunolabelling in primary operable breast cancer

The prognostic value of Ki-67 immunohistochemical labelling was evaluated in 327 operable primary carcinomas of the breast. The follow-up time was up to 4 years (mean 2.7 years). The disease-free survival in Ki-67 positive patients was shorter than in Ki-67 negative patients (P < 0.005). By combining the Ki-67 expression with ER receptors and stage, subgroups with a different disease-free survival were identified. In stage II patients there was a significant difference (P < 0.005) in disease-free survival between Ki-67 positive/ER negative and Ki-67 negative/ER positive patients. In node negative patients there was no such difference. The disease-free survival according to different prognostic factors, stage, ER and node status, were separately examined using a Coxs proportional hazards model. ER (P < 0.0001), the Ki-67 (P < 0.02), tumour size (P < 0.0001) and nodal status (P < 0.006) were independent prognostic factors. We conclude that the potential value of Ki-67 labelling for prognostic evaluation of patients with breast carcinoma is good.

N-acetylcysteine for the prevention of kidney injury in abdominal aortic surgery: a randomized, double-blind, placebo-controlled trial.

In this prospective, randomized, placebo-controlled, double-blind trial we studied the effects of IV N-acetylcysteine for prevention of renal injury in patients undergoing abdominal aortic surgery. Seventy patients without previously documented renal dysfunction were randomly allocated to receive either N-acetylcysteine (150 mg/kg mixed in 250 mL of 5% dextrose infused in 20 min, followed by an infusion of 150 mg/kg in 250 mL of 5% dextrose over 24 h) or placebo. The infusion was started after the induction of anesthesia. The primary outcome measure was renal injury as measured by the increases in urinary N-acetyl-β-d-glucosaminidase (NAG)/creatinine ratio (indicator of renal tubular injury) and urinary albumin/creatinine ratio (indicator of glomerular injury). Renal function was assessed by measuring plasma creatinine and serum cystatin C concentrations. The urinary NAG/creatinine ratio increased significantly from baseline to before crossclamp and remained increased on day 5 in both groups. The urinary albumin/creatinine ratio increased significantly from baseline to 6 h after declamping in the N-acetylcysteine group. However, the changes in the NAG/creatinine ratio and the albumin/creatinine ratio were not significantly different between the two groups. Plasma creatinine and serum cystatin C values remained unchanged during the study period in both groups. In conclusion, N-acetylcysteine did not offer any significant protection from renal injury during elective aortic operation in patients with normal preoperative renal function, and some degree of tubular injury seems to occur before aortic crossclamp.

ANKLE BRACHIAL INDEX MEASUREMENTS IN CRITICAL LEG ISCHAEMIA - THE INFLUENCE OF EXPERIENCE ON REPRODUCIBILITY

Background and Aims: While the use of ankle brachial indices (ABI) in the screening for peripheral arterial obstructive disease is widely accepted, the applicability of ABI in the identification of critical leg ischaemia (CLI) is far from settled. The aim was to assess inter-observer variability of ABI measurements in patients with CLI. Material and Methods: The study was conducted in two parts. In both parts a handheld 9.5 MHz Doppler device was used. Part A: ABI was measured by 7 measurers with variable measurement experience in 22 limbs of patients admitted to the surgical ward because of CLI. The agreement between the measurements was assessed. Part B: Inter-observer agreement in measuring ABI was assessed between 2 trained vascular technicians measuring 33 limbs in patients with CLI on the vascular outpatient clinic. Results and Conclusions: Part A: 16 % of the ABI-values differed 0.15 or more from the median and the mean coefficient of variation was 56.1. Part B: The difference between measurements did not exceed 0.14 with a mean coefficient of variation of 3.2. To obtain reproducible and quantitative measurement values the measurements have to be performed by trained personnel. Measurements performed by untrained personnel can only be regarded as qualitative.

Ki-67, p53, Er-Receptors, Ploidy and S-Phase as Prognostic Factors in T1 Node Negative Breast Cancer

The prognostic value of Ki-67, p53 and ER immunohistochemical labelling and flow-cytometric S-phase fraction and ploidy was evaluated in 212 pT1N0M0 breast carcinomas. The mean follow-up time was 8.3 years. Patients with breast carcinomas with high Ki-67 expression (> or = 10%) had a less favourable disease-free survival than those with low Ki-67 expression (< 10%) (p = 0.008). A positive p53 staining and high SPF were associated with a less favourable disease-free survival although it did not reach statistical significance. The subset of patients with ER negative, Ki-67 > or = 10% and p53 > or = 20% tumours, had a shorter disease-free survival compared with that of all the other patients (p = 0.03). We conclude that the potential value of Ki-67 labelling for prognostic evaluation of T1N0M0 breast carcinoma is good.

Preoperative assessment of proliferative activity and hormonal receptor status in carcinoma of the breast: A comparison of needle aspiration and needle-core biopsies to the surgical specimen

The applicability and reliability of estimates of proliferative activity in breast carcinomas using fine‐needle aspiration (FNA) and needle‐core biopsies (NC) was evaluated in 98 breast carcinoma patients. The Ki‐67, Estrogen receptor (ER), and progesterone receptor (PR) immunolabelling of FNA and NC was compared with that of the surgical specimen. A statistically significant consistency between labelling was found in the Ki‐67‐NC (κ=0.474), ER‐FNA (κ=0.318), ER‐NC (κ=0.518), and PR‐FNA (κ=0.404) groups. The consistency in the Ki‐67‐FNA group was less significant (κ=0.182), and there was no consistency in the PR‐NC group (κ=0.062). There was a positive correlation of Ki‐67 labelling in FNA and NC biopsies (Spearman rank, p=0.4; P=0.0007), and also in ER labeling (Spearman rank p=0.6; P=0.0001. These results indicate that NC and FNA can be used for preoperative assessment of proliferative activity and hormonal status in breast carcinoma. Diagn Cytopathol 1996; 15:205–210.

Ki-67, p53, ER Receptors, Ploidy and S Phase as Long-Term Prognostic Factors in T1 Node-Negative Breast Cancer

Background: The aim of the present study was to evaluate a series of biomarkers with regard to long-term prognostic value in patients with T1 (≤2 cm) node-negative breast cancer. Method: The prognostic value of Ki-67, p53, oestrogen receptor (ER) immunohistochemical labelling, flow-cytometric S phase fraction and ploidy was evaluated in 212 patients with pT1N0M0 breast cancer. The median follow-up time was 15.9 years (range 0.2–27.2 years). Results: In an analysis of breast cancer-specific survival up to 5 years, high Ki-67 (≧10%; p = 0.002), high p53 (≧20%; p = 0.01), negative ER (<30%; p = 0.01) as well as aneuploidy of the tumour (p = 0.02) were significant prognostic factors. When the follow-up was extended to 10 years, only Ki-67 (p = 0.03) was significantly associated with outcome and beyond 15 years none of the studied markers provided significant prognostic information when analyzed separately. There was a weak but significant difference in long-term survival when patients with a combination of high Ki-67 (≧10%), high SPF (>3%) and high p53 (≧20%) were compared to patients with other combinations (p = 0.03). Conclusion: According to the results of our series, it seems that several prognostic markers which are associated with short-term survival (≤5 years) in pT1N0M0 breast cancer may not be significant predictors of long-term (>15 years) breast cancer-specific survival.

Infra‐inguinal Percutaneous Transluminal Angioplasty for Limb Salvage: A Retrospective Analysis in a Single Center

Purpose: To review the feasibility of infra‐inguinal angioplasty in the management of critical limb ischemia (CLI). Material and Methods: Data on 221 patients with 230 critically ischemic limbs, treated with consecutive percutaneous transluminal angioplasty (PTA) at Helsinki University Central Hospital between January 2000 and December 2002 were collected and analyzed retrospectively. Patency, limb salvage, and survival rates were calculated on an intention‐to‐treat basis. Comparisons were done with univariate (Kaplan‐Meier) and multivariate analysis (Cox regression). Results: Overall primary patency, secondary patency, limb salvage, and survival rates were 47%, 59%, 92%, and 76%, respectively, at 12 months. In the multivariate analysis, low toe pressure (⩽30 mmHg) was a significant risk factor for poor patency. Uremia with hemodialysis, low toe pressure (⩽30 mmHg), and hemodynamic failure of the endovascular procedure were found to increase significantly the risk of amputation. Uremia with hemodialysis, coronary artery disease, tissue loss as indication for PTA (Fontaine stage IV), and age over 70 years were all found to increase significantly the risk of death. Conclusion: Infra‐inguinal PTA is feasible in patients with CLI and resulted in good limb salvage.

Are Adverse Events after Carotid Endarterectomy Reported Comparable in Different Registries

OBJECTIVES To assess the extent of discrepancies between different vascular registries, at various levels of validation, and to investigate whether such differences might alter the morbidity and mortality rates obtained from the gold standard dataset for carotid endarterectomy (CEA). METHODS All CEA operations in Helsinki University Central Hospital from 2000-2005 were retrieved from the local vascular registry (HUSVASC) and the Hospital Discharge Registry (HILMO). Both registries were validated at different levels to form the final dataset. Total and indication-specific perioperative morbidity and mortality rates were estimated from each level of validation and compared with those from the final dataset and with pooled rates from systematic reviews. RESULTS Initial search provided 675 and 681 CEAs from HUSVASC and HILMO, respectively, decreasing to 636 (94%) and 614 (90%) when using the specific operative codes for thrombendarterectomy and patch angioplasty. Manual verification of initial HUSVASC results proved that 655 (97%) operations were true CEAs. 18 further proven CEAs, registered only in HILMO, were added to form the final CEA dataset (n=673). The peri-operative morbidity and combined morbidity and mortality rates were 2.23% and 2.67%, respectively. Comparable rates were obtained from both registries, irrespective the level of verification. CONCLUSION Registry data do not appear to be biased by random loss of some operations and thus they are reliable for decision-making. However, further research is still needed to estimate the permissible volume of omissions in a registry for the data-base to remain trustworthy.

The Prognostic Value of Epidermal Growth Factor Receptor (EGFR) in Breast Cancer Patients: Results of a follow-up study on 149 patients

The expression of epidermal growth factor receptor (EGFR) in breast cancer patients was correlated to the disease-free survival. The study included 149 breast cancer patients. The mean follow-up time was 4.2 years. There was an inverse correlation between EGFR and estrogen receptor (p < 0.003) and progesterone receptor (p < 0.013). Subdivision of EGFR showed that patients with EGFR > or = 0.60%, regarded as EGFR positive, had a worse prognosis than patients with EGFR binding < 0.60%, regarded as EGFR negative (p = 0.004). In the ER negative group, EGFR positive patients had a shorter relapse-free time than patients with EGFR negative cancer (p < 0.009). The same subdivision among ER positive patients showed no statistically significant difference.