Axillary lymph node status,but not tumor size,predicts locoregional recurrence and overall survival after mastectomy for breast cancer

OBJECTIVE: To assess the significance of axillary lymph node status and tumor size for predicting locoregional recurrence (LRR) and overall survival after mastectomy for breast cancer and to discuss the utility of postmastectomy radiation therapy. SUMMARY BACKGROUND DATA: Patients with locally advanced breast cancer require multimodality treatment combining chemotherapy (and/or hormonal therapy), surgery, and radiation. Randomized trials have demonstrated that postmastectomy radiation reduces LRR, but no overall survival benefit has been established. METHODS: Criteria for accrual to the Alabama Breast Cancer Project (1975-1978) were female gender and T2-3 breast cancer with M0 status. Patients underwent a radical or a modified radical mastectomy. Node-positive patients received adjuvant cyclophosphamide, methotrexate, and fluorouracil chemotherapy or adjuvant melphalan. Patients were evaluated for LRR and overall survival based on the number of positive axillary lymph nodes and (in N0 patients) pathologic tumor size. Significance was determined using chi-square analysis. Survival curves were generated using the Kaplan-Meier method and were compared by log-rank analysis. RESULTS: After median follow-up of 15 years, neither type of surgery nor chemotherapy was shown to affect locoregional disease-free or overall survival. LRR rates were higher and overall survival rates were lower in patients with nodal involvement, while tumor size was not shown to significantly affect these rates. CONCLUSIONS: Patients with axillary lymph node metastases may benefit from postmastectomy radiation, but the use of postmastectomy radiation in N0 patients is not supported when it is based on tumor size alone.     

Results of long-term follow-up for transanal excision for rectal cancer

Low anterior resection and abdominoperineal resection are the surgical techniques used most frequently in the treatment of rectal cancer. It is our hypothesis that selected patients with early T stage, well or moderate grade of differentiation, and small tumor size are good candidates for transanal excision in terms of minimal morbidity, low recurrence rate, and sphincter preservation. From January 1993 until August 2001 30 patients underwent transanal excision; three patients were excluded because they had histology other than adenocarcinoma. Factors analyzed included those related to the patient [age (years), gender, race, body mass index, and anal tone], tumor [size (cm), distance from the anal verge (cm), differentiation, and American Joint Committee on Cancer stage], and additional treatment. Median follow-up of the group was 40.7 months (range 0.6-99) and the primary end points were local and distant recurrence. Data are presented as mean (range). The median age of the group was 58.9 years (range 27-94); 52 per cent were female and 48 per cent were male. The mean body mass index was 25.9 (range 22.7-36.7). Preoperatively 81, 11, and 4 per cent of the patients had stage I, II, and III/IV cancer, respectively. Preoperative size of the tumor was 2.0 cm (1-3 cm), and distance from the anal verge was 5.0 cm (3-15 cm). Blood loss was 50 cm3 (5-200 cm3), and there were no operative complications. Tumor differentiation levels were well (37%) and moderate (63%). All patients had negative margins. Additional treatment consisted of radiation therapy in seven patients (six postoperative and one preoperative). Chemotherapy was given to seven patients (six postoperative and one preoperative). The local recurrence rate was 7.4 per cent (two patients), and 3.7 per cent recurred distantly (one patient). Transanal excision of low rectal cancer in selected patients is an acceptable alternative to formal resection. Important selection criteria include early T stage, well or moderate differentiation, relatively small tumor size, and negative microscopic margins. The roles of radiation and chemotherapy remain controversial.     

Administration of milrinone before ischemia, in the presence of beta-blockade, to treat metabolic impairment and myocardial stunning in pigs

Background: We examined effects of phosphodiesterase type III inhibition on regional myocardial metabolism and global left ventricular function, during ischemia, in the presence of β-blockade.
Methods: Twenty-three pigs were randomized and studied to completion in four groups: C, did not receive drugs; M, received 50 μg/kg milrinone; E, received esmolol (150 μg/kg/min); E+M, received both. The left anterior descending artery (LADa) was then occluded for 15 min, followed by a 60-min reperfusion. Left ventricular (LV) function data obtained included LV pressures, cardiac output (CO), slope of end-systolic pressure–volume relationship (Emax), and dP/dT. Blood lactate concentrations were obtained from the aorta, LADa, and vein at baseline, end of occlusion, and during early (5 min) and late (1 h) reperfusion.
Results: During ischemia, occlusion produced significant depression in LV dP/dT, Emax and concomitant elevation of LVEDP that persisted over early reperfusion in groups not treated with milrinone. After ischemia, measurements of CO were higher, with lower LVEDP and SVR; LV dP/dT and the Emax were higher, with lower LVEDP in the E+M group vs. the E group. Ischemic region lactate extraction during ischemia was better with E group vs. C group. Esmolol without or with milrinone was associated with nonsignificant lactate ischemic production during early reperfusion from baseline values.
Conclusion: We demonstrated that the pre-emptive administration of milrinone before ischemia was associated with less ischemic hemodynamic effects, without worsening the ischemic metabolic process. The combination E+M diminished ischemic metabolic impairment, and preserved left ventricular function and baseline hemodynamics.     

Multi-detector computed tomography in coronary artery bypass graft assessment: a meta-analysis

Multi-detector computed tomography (MDCT) has become an alternative to coronary angiography in diagnosis of graft occlusion and stenosis after coronary artery bypass. A literature search was performed for studies comparing angiography to 8-slice, 16-slice, and 64-slice MDCT in the assessment of coronary grafts. In assessing occlusion, 14 studies produced pooled sensitivity of 97.6%, specificity of 98.5%, diagnostic odds ratio of 934.2, area under the curve of 0.996, and Q* of 0.977. Ninety-six percent of all grafts were visualized for occlusion assessment. Beta blockers, symptomatic status, and postoperative period did not significantly affect diagnostic performance. Stenosis assessment produced sensitivity of 88.7% and specificity of 97.4%. Eighty-eight percent of patent grafts could be assessed for stenosis. The diagnostic accuracy of MDCT approaches angiography for diagnosing graft occlusion and stenosis in patients with venous and arterial coronary bypass grafts. Our findings show that cardiac surgeons will need to interpret MDCT images of both native and grafted vessels soon in preparation for primary or re-do coronary bypass grafting procedures.     

Arteriovenous malformation mimicking a renal-cell carcinoma

We describe a renal arteriovenous malformation in a patient with a 1-month history of flank pain. Imaging studies were interpreted as being consistent with renal-cell carcinoma. However, Doppler ultrasonography demonstrated turbulent blood flow, and selective renal angiography confirmed the diagnosis of an arteriovenous malformation. Embolization relieved the pain. This case calls attention to the need to consider arteriovenous malformations in the differential diagnosis of central homogenously enhancing renal lesions.     

Retinal input to the suprachiasmatic nucleus before and after puberty in Djungarian hamsters

Retinal projections to the suprachiasmatic nucleus (SCN) mediate the effect of photoperiod to entrain circadian rhythms and to control reproductive maturation in the Djungarian hamster. To determine whether the retinal innervation of the SCN had fully developed by the onset of puberty in this hamster species, prepubertal and postpubertal hamsters received an intraocular unilateral injection of horseradish peroxidase (HRP), and after 24 h, the anterograde transport of HRP to the SCN was studied. In prepubertal hamsters, the retinohypothalamic tract (RHT) was found to project to the medial and caudal SCN, principally the ventrolateral regions and, to an extent, the dorsomedial portion of the nucleus. RHT innervation was asymmetric; the SCN contralateral to the monocular injection received the dominant projection. A similar pattern of retinal projections was found postpubertally; however, the ipsilateral SCN was less extensively labelled with HRP and smaller as determined by Nissl counterstain compared to that in prepubertal hamsters. These findings indicate that modifications in the retinal innervation of the SCN occur as late as puberty, and may be part of a developmental change in the mechanism which processes photoperiodic information during sexual maturation.     

Interleukin-4 enhances the survival of severe combined immunodeficient mice engrafted with human B-cell precursor leukemia

Human interleukin-4 (huIL-4) has been shown to inhibit the growth in vitro of cells from patients with acute lymphoblastic leukemia (ALL). With the aim of determining whether this cytokine might be useful in the treatment of patients with ALL, the effects of huIL-4 on human B- cell precursor ALL engrafted in severe combined immunodeficient (SCID) mice were examined. The inhibition of [3H] thymidine uptake of primary ALL cells by huIL-4 was maintained following engraftment and passage of leukemia in SCID mice. Five of seven xenograft leukemias showed significant inhibition in vitro by huIL-4 at concentrations as low as 0.5 ng/mL; furthermore, huIL-4 counteracted the proliferative effects of IL-7. When used to treat two human leukemias engrafted in SCID mice, huIL-4 200 microgram/kg/d, as a continuous 14-day subcutaneous infusion, suppressed the appearance of circulating lymphoblasts and extended survival of mice by 39% and 108%, respectively, the first demonstration of IL-4 activity against human leukemia in vivo. The mean steady-state huIL-4 level in mouse plasma during the infusion was 1.46 ng/mL (SEM +/- 0.14 ng/mL), which was similar to concentrations found to be effective in vitro. ALL cells obtained from mice relapsing after huIL-4 treatment continued to show inhibition by the cytokine in vitro. These data suggest that IL-4 may be useful in the treatment of patients with ALL.     

Factor VIII-induced superaggregation of human platelets

High concentrations of bovine factor VIII cause clumping of platelets into a few very large aggregates. This response is termed superaggregation. It is distinct from factor-VIII-induced agglutination but is also independent of both extracellular calcium ions and platelet energy metabolism. Neither agglutinating lectins nor aggregating agents, including thrombin, ADP, the ionophore A23187, and U46619, a prostaglandin analog, can induce superaggregation, even at very high concentrations. Washed platelets undergo superaggregation, and superaggregation does not increase the amounts of fibrinogen or albumin trapped by agglutinated platelets. It is not inhibited by membrane- stabilizing drugs or by colchicine or cytochalasin-B. Formaldehyde and glutaraldehyde prevent superaggregation without affecting the binding of radiolabeled factor VIII to the platelets. Superaggregated platelets are separated by approximately 50 nm and are not shape-changed or degranulated. In adenosine diphosphate (ADP) induced aggregation, the platelets are distorted and only 30 nm apart. Superaggregation is reversed by dextran sulfate, and the dispersed platelets are still able to respond to ADP. Our observations are consistent with the binding of high molecular weight multimers of bovine factor VIII to more than one receptor on each platelet, with superaggregation occurring through recruitment of additional receptors. This process may be interrupted by protein crosslinking reagents, such as formaldehyde and glutaraldehyde.