Sequential estrogen receptor determinations from primary breast cancer and at relapse: prognostic and therapeutic relevance. The International Breast Cancer Study Group (formerly Ludwig Group).

We retrospectively evaluated 401 selected patients who had estrogen receptor (ER) assays both at primary surgery and at relapse in an accessible site to determine the clinical relevance of the subsequent ER determination. The median time between ER assessments was 27 months (range: 2-122 months). The median follow-up time from diagnosis was 6 years (range: 2-12 years). For patients with ER+ tumors at primary diagnosis, 29% (76/261) had ER- tumors at relapse, while for ER- primaries, the conversion rate was 33% (46/140). Conversions from ER+ to ER- occurred more often when the time interval between assays was less than one year (p = 0.004), while conversions from ER- to ER+ tended to occur late (beyond three years; p = 0.0003). Treatments received between assays (usually adjuvant therapy) had only a slight influence on ER status conversion. Post-relapse survival was poor for patients who had the biopsy accessible recurrence within one year; an expression of the aggressive nature of the disease. Among patients whose accessible relapse was beyond one year, those with ER- primaries who converted to ER+ had a longer survival than those whose recurrence was classified again as ER- (p = 0.006). This group of patients with ER- primaries who recurred beyond one year with an ER+ tumor in an accessible site represented 29% (40/140) of all patients with ER- primaries and had an estimated overall survival rate of more than 60% at 6 years from the accessible relapse. ER determination upon relapse within one year has very little clinical relevance.(ABSTRACT TRUNCATED AT 250 WORDS)     

Management of thoracoabdominal aneurysm type IV.

BACKGROUND: Thoracoabdominal aneurysm type IV (TAA IV) represents only a minority of aortic aneurysms, but as it is an entirely abdominally located aneurysm, vascular surgeons are likely to see such aneurysms in their practice. The current surgical management of TAA IV is reviewed. METHODS: A PubMed/Medline-literature search for TAA IV. RESULTS AND CONCLUSIONS: A detailed preoperative evaluation to determine the rupture and operative risk is required. A threshold size of 5.5-6 cm is recommended for elective repair of TAA IV, which then is adjusted for age and other risk factors. Operative simplicity with the clamp and sew approach to obtain a short aortic cross-clamp time seems to have most support in the literature. The necessity of adjunct treatment to prevent visceral and spinal cord ischemia seems to be needed rarely. Uncomplicated repair has a minimal risk of neurological injury and a low risk of renal failure requiring dialysis in patients without preoperative renal dysfunction or renal artery stenosis. The role of endovascular repair of these aneurysms remains to be established.     

Is the humoral renal antihypertensive activity of the spontaneously hypertensive rat (SHR) reset to the high blood pressure?

The kidneys have a humoral antihypertensive system, located in the renal medulla and presumably antagonizing the pro-hypertensive renin-angiotensin system. Medullipin I and II and maybe platelet activating factor (PAF), seem to be the mediators of this system, known to be activated after reversal of renovascular hypertension or when the perfusion pressure to a normotensive kidney is suddenly elevated. The present study was undertaken to investigate whether this system is functioning also in the spontaneously hypertensive rat (SHR), and if it is then reset in proportion to the increased mean arterial pressure (MAP). Isolated kidneys from spontaneously hypertensive rats and from Wistar Kyoto rats (WKY) were cross-perfused in vivo from anaesthetized intact Wistar Kyoto rat 'donors'. After 30 min of perfusion at 100 mmHg the perfusion pressure to the isolated kidneys were, for 60 min, either kept unaltered at 100 mmHg or, for the Wistar Kyoto rat kidneys, increased to 150-200 mmHg and, for the spontaneously hypertensive rat kidneys, raised to 200 or 250 mmHg. The results show that the humoral antihypertensive system is present also in spontaneously hypertensive rat kidneys, but is here reset upwards to or even beyond the elevated MAP level. Furthermore, all mean arterial pressure reductions caused by high-pressure perfusion of Wistar Kyoto and spontaneously hypertensive rat kidneys were accompanied by reductions in heart rate (HR) in the 'donors', in agreement with previous observations after reversing renal hypertension and after i.v. medullipin I injection. In fact, in spontaneously hypertensive rat kidneys, the 'incretory' depressor mechanism appears to be more markedly reset upwards than is the 'excretory' depressor mechanism inherent in pressure diuresis with consequent salt-volume elimination. In conclusion spontaneously hypertensive rats, like Wistar Kyoto rats and Wistar rats, have a humoral antihypertensive system in the kidneys, but it is reset upwards even beyond the elevated mean arterial pressure level in spontaneously hypertensive rats. The combination of a depressor response and reduced heart rate in the 'donors' renders further evidence that the medullipins are the principal, though probably not the only, humoral antihypertensive factors released from the cross-circulated kidneys.     

Menstrual cycle and timing of breast surgery in premenopausal node-positive breast cancer: Results of the International Breast Cancer Study Group (IBCSG) Trial VI

Purpose: It has been postulated that breast cancer surgery performedduring the follicular phase of the menstrual cycle is associated with pooreroutcome.Patients and methods: We tested this hypothesis by evaluatingdisease-free survival (DFS) for 1033 premenopausal patients who receiveddefinitive surgery either during the follicular phase (n = 358) or theluteal phase (n = 675). All patients were enrolled in a randomized trialconducted between July 1986 and April 1993. All had node positive breastcancer and randomization was stratified by estrogen receptor (ER) status.All patients received at least three cycles of adjuvant cyclophosphamide,methotrexate, and 5-fluorouracil (CMF). The median follow-up was 60 months.Results: Patients who underwent definitive surgery for breast cancer inthe follicular phase had a slightly worse disease-free survival than thoseoperated on during the luteal phase (five-year DFS percentage: 53%versus 58%; hazard ratio, 1.13; 95% confidence interval (CI),0.94–1.38; P = 0.20). The effect was significantly greater for thesubpopulation of 300 patients with ER-negative primaries (P = 0.02interaction effect; five-year DFS percentages 42% vs. 59%;hazard ratio 1.60; 95% CI, 1.12–2.25; P = 0.008). The effect oftiming of surgery diminished for analyses based on lesser surgicalprocedures, e.g., excisional biopsies. In particular, no effect of timingwas observed for fine needle aspiration procedures.Conclusions: Surgical procedures which are more extensive than a fineneedle aspiration biopsy might be associated with worse prognosis if conductedduring the follicular phase of the menstrual cycle. This phenomenon was seenpredominantly for high risk breast cancer with low levels or no estrogenreceptors in the primary tumor.     

Interventional treatment of children with portal hypertension secondary to portal vein occlusion.

PURPOSE: To present methods and results of interventional treatment of children with portal hypertension (PH) secondary to portal vein occlusion (PVO). MATERIAL AND METHODS: Five children, four boys and one girl, 8 - 14 years old, with symptomatic PH secondary to PVO were treated. All children had one or more episodes of bleeding from oesophageal varices, enlarged spleen and thrombocytopenia. Partial embolisation of the spleen was performed in four children. Attempts to recanalize the occluded part of the portal vein were done in all children using transjugular (n = 4), transhepatic (n = 4) and transsplenic (n = 3) approaches. RESULTS: All procedures were carried out without serious complications and were followed by normalisation of the platelet count, decrease in splenic size and disappearance of bleeding. Recanalisation of the occluded portal vein with a stent was possible in one child and partial stent recanalisation was possible in another child. Transjugular intrahepatic portosystemic shunt (TIPS) with partly extrahepatic, intraperitoneal route was created in one patient. All children were scheduled for follow-up. During the observation time of 22 months (5 - 46 months), additional balloon dilation and placement of new stents were necessary in two children. CONCLUSION: Interventional procedures are valuable in the treatment of children with symptoms secondary to PVO. Treatment should be customized and scheduled follow-ups of the patients are necessary.     

The human epidermis models EpiSkin, SkinEthic and EpiDerm: an evaluation of morphology and their suitability for testing phototoxicity, irritancy, corrosivity, and substance transport.

The commercially available reconstructed human epidermis models EpiSkin, SkinEthic and EpiDerm demonstrate reasonable similarities to the native human tissue in terms of morphology, lipid composition and biochemical markers. These models have been identified as useful tools for the testing of phototoxicity, corrosivity and irritancy, and test protocols have been developed for such applications. For acceptance of these tests by the authorities, prevalidation or validation studies are currently in progress. Furthermore, first results also indicate their suitability for transport experiments of drugs and other xenobiotics across skin. Still, however, the barrier function of these reconstructed human epidermis models appears to be much less developed compared to native skin. Further adaptation of the models to the human epidermis, especially concerning the barrier function, therefore remains an important challenge in this area of research.     

Timing of CMF chemotherapy in combination with tamoxifen in postmenopausal women with breast cancer: role of endocrine responsiveness of the tumor.

BACKGROUND: Controversy persists about whether chemotherapy benefits all breast cancer patients. PATIENTS AND METHODS: In the International Breast Cancer Study Group (IBCSG) trial VII, 1212 postmenopausal patients with node-positive disease were randomized to receive tamoxifen for 5 years or tamoxifen plus three concurrent courses of cyclophosphamide, methotrexate and 5-fluorouracil ('classical' CMF) chemotherapy, either early, delayed or both. In IBCSG trial IX, 1669 postmenopausal patients with node-negative disease were randomized to receive either tamoxifen alone or three courses of adjuvant classical CMF prior to tamoxifen. Results were assessed according to estrogen receptor (ER) content of the primary tumor. RESULTS: For patients with node-positive, ER-positive disease, adding CMF either early, delayed or both reduced the risk of relapse by 21% (P=0.06), 26% (P=0.02) and 25% (P=0.02), respectively, compared with tamoxifen alone. There was no difference in disease-free survival when CMF was given prior to tamoxifen in patients with node-negative, ER-positive tumors. CONCLUSIONS: CMF given concurrently (early, delayed or both) with tamoxifen was more effective than tamoxifen alone for patients with node-positive, endocrine-responsive breast cancer, supporting late administration of chemotherapy even after commencement of tamoxifen. In contrast, sequential CMF and tamoxifen for patients with node-negative, endocrine-responsive disease was ineffective.     

Regional renal haemodynamics of angiotensin II infusion under prostaglandin, kinin or converting enzyme inhibition in the Wistar rat

AIMS: Renal medullary blood flow is important in blood pressure regulation and is surprisingly unaffected by the vasoconstrictor action of angiotensin II (Ang II). This study tested if the effect of Ang II on the renal papillary circulation is modulated by bradykinins, prostaglandins or NO (NO). In anaesthetised Wistar rats, total renal blood flow (RBF) was measured, as was cortical (CBF) and papillary (PBF) blood flow, using the laser-Doppler technique, in responses to Ang II (30 ng kg(-1) min(-1)) alone and after ACE inhibition (enalapril) or bradykinin/prostaglandin synthesis inhibition (ketoprofen, aprotinin). PBF was also measured after blockade of NO formation with or without pretreatment with an Ang II receptor antagonist (losartan). MAJOR FINDINGS: (i) PBF did not change in response to Ang II infusion but MAP increased (+ 10%) and RBF and CBF decreased. (ii) Treatment with aprotinin and ketoprofen left MAP, RBF and CBF unchanged but decreased PBF. Ang II did not decrease PBF further but a significant increase in MAP was seen. (iii) Enalapril treatment left PBF unchanged but decreased MAP and increased RBF and CBF. When Ang II was infused PBF and MAP increased markedly. (iv) L-NAME reduced PBF independently of losartan treatment. PRINCIPAL CONCLUSION: Bradykinin and prostaglandins do not appear to cause the lack of renal papillary vasoconstriction to Ang II. However, the increase in PBF to Ang II seen after enalapril treatment suggests that enalapril treatment, possibly via its effects on kinin breakdown and subsequent NO formation, might affect the sensitivity of renal papillary autoregulation. This may be an important aspect of the blood pressure lowering effect of ACE inhibitors.