Abstract only
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Background: The role of bisphosphonates when added to the neoadjuvant treatment of BC in enhancing the efficacy of therapy is still unknown. Methods: NEOZOTAC is a national, ...multicenter, randomized study comparing the efficacy of TAC (docetaxel, Adriamycin and cyclophosphamide i.v.) CT followed by G-CSF on day 2 with or without ZA 4 mg i.v. ,q 3 weeks in patients (pts) with stage II/III, measurable, HER2-negative BC and absence of prior bisphosphonate usage. The primary endpoint is the pathologic complete response (pCR) rate in the resection specimen and positive lymph nodes. 228 pts are needed to show an improvement of the pCR rates from 17% to 34% in the experimental arm using a 5% significance level based on the two-sided Fisher’s exact test with a power of 80%. Randomization was done by using the Pocock’s minimisation technique stratified by cT, cN and estrogen receptor status. pCR rate was analyzed using the Cochran-Mantel-Haenszel test, adjusting for the stratification factors. Analysis was based on intent-to-treat. An unplanned subgroup analysis of postmenopausal women (PMW; FSH >20 and estradiol <110) and baseline vitamin D levels was performed. Results: From July 2010 to April 2012, 250 patients from 25 participating sites were randomized. Pathologic response data of 228 patients are currently available. pCR rate did not differ between the two study arms (17% vs 16%, p = 0.81). However, a trend in benefit in favor of ZA was observed in PMW (18% vs 11%, OR 1.90, 95% C.I. 0.52 – 6.88). Patients with severe vitamin D insufficiency (<25 nmol/L) seemed to respond worse to CT numerically (6% vs. 18%). At ASCO pCR and clinical response data of all patients will be reported. Conclusions: Previously, we have shown that adding ZA to neoadjuvant CT is safe with good compliance.In this study, treatment with ZA did not result in a pCR benefit in the total study population. However our findings suggest that addition of ZA to neoadjuvant CT might be effective for enhancing response in PMW with BC. Clinical trial information: NCT01099436.
To compare digital subtraction angiography with three-dimensional phase-contrast magnetic resonance (MR) angiography in detection of significant renal artery stenosis.
Sixteen patients underwent ...digital subtraction angiography and systolically gated three-dimensional phase-contrast MR angiography within 1 week. Scoring of stenosis on MR angiograms was based on presence and length of a flow void and quality of flow signal intensity in the distal part of the artery. Intraarterial pressure measurement was the reference standard for hemodynamically significant renal artery stenosis.
MR angiography depicted two of five patent accessory arteries. Comparison of digital subtraction angiography and MR angiography with intraarterial pressure measurements was possible in 25 main renal arteries. In 13 arteries, a pressure gradient of more than 15 mm Hg was found. Digital subtraction angiography depicted 10 of these stenoses (sensitivity, 77%; specificity, 92%). A flow void was present at MR angiography in eight stenoses (sensitivity, 62%; specificity, 83%). In 12 of the stenosed vessels, distal flow signal intensity was impaired at MR angiography (sensitivity, 92%; specificity, 75%). There was no difference between the two modalities (P > .05) in grading hemodynamic significance of renal artery stenosis.
Systolically gated MR angiography and digital subtraction angiography are equally effective in depicting hemodynamically significant stenoses in the main renal arteries. MR angiography, however, is not adequate in depiction of accessory renal arteries.
Chronic splanchnic ischaemia van Bockel, J.Hajo; Geelkerken, Robert H.; Wasser, Martin N.
Baillière's best practice & research. Clinical gastroenterology,
02/2001, Letnik:
15, Številka:
1
Journal Article
Recenzirano
Chronic splanchnic ischaemia is a relatively unusual clinical entity consisting of pain and/or weight loss and caused by chronic splanchnic disease (i.e. stenosis and/or occlusion of the coeliac and ...superior mesenteric artery). The occlusive disease is usually caused by atherosclerosis and is in itself not rare in older individuals. Extensive collateral circulation can develop between the three splanchnic arteries and may compensate for the decreased splanchnic perfusion over time. The pathophysiology of chronic splanchnic ischaemia has still not been completely elucidated.
A reliable diagnosis of chronic splanchnic ischaemia, based on a proven causal relationship between the occlusive disease and the symptoms, can be very difficult. Traditionally, tests for evaluating the haemodynamic consequences of the vascular stenoses were not available. Important improvements in establishing a more reliable diagnosis have been achieved with duplex ultrasound and magnetic resonance evaluation of the splanchnic circulation. Tonometry is another promising functional test that may prove useful not only for gaining greater insight into the pathophysiology of chronic splanchnic ischaemia but also for the clinical evaluation of this syndrome.
The natural history of chronic splanchnic disease suggests that progressive disease may result in acute mesenteric ischaemia. Surgical reconstruction of the coeliac and/or the superior mesenteric artery is the therapeutic standard with excellent short and long-term results. Satisfactory early results using angioplasty with or without stent suggest that this type of intervention may relieve symptoms in selected patients with a higher surgical risk.
RATIONALE AND OBJECTIVESTo evaluate 4 doses of gadobenate dimeglumine (Gd-BOPTA) for contrast-enhanced magnetic resonance angiography (CE-MRA) of the pelvic arteries and to compare CE-MRA with ...unenhanced time-of-flight MRA (2D-TOF-MRA).
METHODSA multicenter Phase II dose-finding study was performed in 136 patients with Gd-BOPTA doses of 0.025, 0.05, 0.1, and 0.2 mmol/kg bodyweight. Evaluation of CE-MRA images and comparison with 2D-TOF-MRA images was performed onsite and by 2 blinded offsite reviewers in terms of subjective image quality, number of lesions detected, and confidence in lesion characterization.
RESULTSSignificant (P < 0.05) improvements over unenhanced findings were observed for CE-MRA at all dose levels. For reviewer 1 and the onsite investigators, the overall image quality increased up to a dose of 0.1 mmol/kg and then plateaued. For reviewer 2, increased image quality was noted up to a dose of 0.2 mmol/kg. Significant (P < 0.005) increases in diagnostic confidence on CE-MRA versus unenhanced MRA was observed for all dose groups by reviewer 1 and the onsite investigators and for the 0.1 and 0.2 mmol/kg dose groups by reviewer 2. No serious adverse events were recorded that were attributable to the study drug and no trends in laboratory parameters, vital signs, or electrocardiogram recordings were observed.
CONCLUSIONSGadobenate dimeglumine-enhanced MRA is safe and significantly more effective than unenhanced 2D-TOF-MRA for imaging the pelvic arteries. A dose of 0.1 mmol/kg appears the most appropriate dose for subsequent Phase III clinical evaluation.
To test the hypothesis that increased blood flow in the superior mesenteric artery (SMA) reflects disease activity in patients with Crohn disease.
Duplex Doppler sonographic measurements of SMA blood ...flow volume were obtained in 10 patients with active Crohn disease, 10 patients with chronic inactive Crohn disease, and 10 healthy volunteers. Disease activity was determined with clinical and laboratory indicators.
Interstudy reproducibility of repeated SMA flow volume measurements was good (r = .98). A marked increase in SMA flow volume was noted in patients with active disease compared with patients with inactive disease and healthy volunteers: 1,588 mL/min +/- 576 versus 288 mL/min +/- 113 and 417 mL/min +/- 147, respectively (P < .05 for both comparisons).
Activity of Crohn disease causes a substantial increase in SMA flow volume. Measurement of SMA blood flow may be an important noninvasive, readily available, inexpensive tool that can be used to monitor Crohn disease objectively.
Our goal was to assess the value of MRA for detecting stenoses in the celiac (CA) and superior mesenteric (SMA) arteries in patients suspected of having chronic mesenteric ischemia, using an ...optimized systolically gated 3D phase contrast technique.
In an initial study in 24 patients who underwent conventional angiography of the abdominal vessels for different clinical indications, a 3D phase contrast MRA technique (3D-PCA) was evaluated and optimized to image the CAs and SMAs. Subsequently, a prospective study was performed to assess the value of systolically gated 3D-PCA in evaluation of the mesenteric arteries in 10 patients with signs and symptoms of chronic mesenteric ischemia. Intraarterial digital subtraction angiography and surgical findings were used as the reference standard.
In the initial study, systolic gating appeared to be essential in imaging the SMA on 3D-PCA. In 10 patients suspected of mesenteric ischemia, systolically gated 3D-PCA identified significant proximal disease in the two mesenteric vessels in 4 patients. These patients underwent sucessful reconstruction of their stenotic vessels.
Cardiac-gated MRA may become a useful tool in selection of patients suspected of having mesenteric ischemia who may benefit from surgery.
AMG 531 is a novel platelet-stimulating peptibody that targets the TPO receptor, resulting in increased production of platelets. This ongoing, open-label study assessed the safety and efficacy of ...long-term AMG 531 dosing in ITP patients. Eligible patients have completed a previous AMG 531 study in ITP, are ≥18 years of age, have a baseline platelet count ≤50 x 109/L, with no recent significant change in medical history. The AMG 531 starting dose is 1μg/kg by SC injection with dose adjustment to an original maximum of 30μg/kg, since reduced to 15μg/kg. Patients are treated weekly unless the platelet count is >400x109/L. Concurrent corticosteroids can be tapered when the platelet count is ≥50x109/L. Preliminary data are available for 26 patients treated for up to 24 weeks: 17 women and 9 men; mean age, 48.4±11.6 (SD) years; mean baseline platelet count, 18.5±12.3 (SD) x109/L. Twenty-one patients (80.8%) had undergone a splenectomy before study entry; 6 (23.1%) were receiving concurrent corticosteroids for ITP. Twenty-one of 26 patients (80.8%) had a protocol-defined platelet response to AMG 531 (doubling of the baseline platelet count and ≥50x109/L). The mean AMG 531 dose at the first response was 3.7±2.7 (SD) μg/kg (at median 5 weeks); the mean dose at week 24 was 7.2±4.2 (SD) μg/kg. Twelve of 26 patients (46.2%) had a durable platelet response (doubling of the baseline count and ≥50x109/L at 6 or more of weeks 17–24). Twenty patients (76.9%) had a platelet count ≥100x109/L at least once; 7 (26.9%) had a platelet count ≥400x109/L. Of 6 patients on concurrent corticosteroids, 3 discontinued treatment and 2 had a ≥25% dose reduction. At least 1 serious adverse event was reported in 4 patients: anal fistula (unrelated to treatment), adverse drug reaction (unrelated), multiple sclerosis relapse (unrelated), bone pain (related), and diffuse reticulin formation in the bone marrow reported as myelofibrosis (related). Reticulin formation is hypothesized as due to excessive accumulation of megakaryocytes in the bone marrow. AMG 531 was discontinued, and a bone marrow 3 months later showed improvement. One patient experienced adverse events (musculoskeletal pain and headache) resulting in withdrawal from the study. No neutralizing antibodies have been detected to date. In summary, repeated exposure to AMG 531 has been generally well tolerated in this ongoing study. A total 80.8% of patients achieved a platelet response, defined as doubling of the baseline count and ≥50x109/L. Individualized weekly doses of AMG 531 may provide a therapeutic option in ITP, potentially enabling patients to taper off long-term corticosteroid therapy.
