Citations

Vascular events that occur in the brain also occur in the eye, giving rise to different ophthalmologic manifestations that range from amaurosis fugax to complete blindness due to central retinal artery occlusion. The objective of this study was to ascertain the relative frequency and predictive value of ocular findings suggestive of carotid occlusive disease in patients being investigated for carotid endarterectomy. The charts of 366 patients undergoing carotid angiography for evaluation of cerebrovascular or visual symptoms over a 5-year period were reviewed. The presence of eye symptoms, neurologic symptoms, cervical bruits, and ophthalmologic findings on admission was recorded and correlated with the presence of significant carotid artery stenosis (? 50%). Positive eye findings included retinal plaques, rubeosis iridis, neovascular glaucoma, venous stasis retinopathy, central and branch retinal artery occlusion, ischemic optic neuropathy, and asymmetric hypertensive retinopathy. Seventy-five patients (21%) presented with amaurosis fugax; 41 patients (11%) were found to have one or more ocular findings consistent with carotid artery disease. All patients with positive eye findings were diagnosed by ophthalmologists, who were consulted in 94 cases. Of these 41 patients, 29 (70.3%) were subsequently shown to have greater than 50% stenosis of the common or internal carotid artery. Ten patients had amaurosis fugax, a carotid bruit, and positive eye findings. All were shown to have a significant carotid stenosis. This study shows that ocular pathology, if diagnosed, is correlated with carotid stenosis, especially if other contributing history and physical findings are also considered.

Previous results following subfascial endoscopic perforator vein surgery were reported to be worse in post-thrombotic syndrome than in limbs with primary valvular incompetence. This report comprises a larger patient cohort with longer follow-up. The goal of this study was to determine if subfascial endoscopic perforator vein surgery is justified in patients with postthrombotic venous insufficiency. The clinical data of 91 consecutive patients who underwent subfascial endoscopic perforator vein surgery with or without superficial reflux ablation over a 7-year period from May 1993 to June 2000 were retrospectively analyzed. Fifty-four females and 37 males (median age, 53 years; range, 20-77) underwent 103 subfascial endoscopic perforator vein surgery procedures. Forty-two limbs were classified as C6 (active ulcer), 34 as C5 (healed ulcer), and 24 as C4 (lipodermatosclerosis). Thirty procedures were performed in post-thrombotic limbs. Concomitant superficial reflux ablation was performed in 74 limbs (72%); saphenous vein stripping had been previously performed in 29 (28%). Deep venous incompetence was present in 89% of limbs; 13% had venous outflow obstruction on plethysmography. Cumulative ulcer healing in post-thrombotic limbs was not significantly different from limbs with primary valvular incompetence; 30-, 60-, and 90-day healing rates were 44%, 72%, and 72% vs 39%, 70%, and 87%, respectively (p = 0.35). On univariate analysis, the presence of ulcer greater than 2 cm in diameter was associated with delayed ulcer healing (p = 0.02). Cumulative ulcer recurrence in all limbs was 4%, 20%, and 27% at 1, 3, and 5 years, respectively. Ulcer recurrence in post-thrombotic limbs was higher than in limbs with primary valvular incompetence at 1, 3, and 5 years; 16%, 47%, and 56% vs 0%, 8%, and 15%, respectively (p = 0.001). Recurrent ulcers were small, superficial, and easier to heal. Clinical improvement was significant even in post-thrombotic limbs; median clinical score decreased from 9.5 to 3 (p=0.001), and median outcome score was +2 (mean 1.9; range, -I to 3). Median clinical score in patients with primary valvular incompetence improved from 6 to 1.5 (p = 0.0001). Subfascial endoscopic perforator vein surgery with superficial reflux ablation promoted ulcer healing, improved clinical outcome, and resulted in a low long-term ulcer recurrence rate in limbs with primary valvular incompetence. Despite good clinical outcome in post-thrombotic limbs, ulcer recurrence was high. These results imply that the role of subfascial endoscopic perforator vein surgery with superficial reflux ablation in patients with post-thrombotic limbs continues to be controversial.

The purpose of this study was to examine the technical aspects of intraoperative duplex ultrasound (DUS) following carotid endarterectomy (CEA), suggest criteria to differentiate significant lesions requiring immediate surgical revision from normal or benign defects, and evaluate how frequently intraoperative DUS provides useful or unsuspected information. A retrospective study was performed on all patients who had both CEA and intraoperative carotid DUS between January 1,1990. and January 1,1995. A total of 155 DUS examinations were performed in 149 patients. Findings were grouped into three categories: normal; minor/insignificant lesions; and hemodynamically significant lesions based on the presence or absence of elevated peak systolic velocities, visible stenosis/thrombus, or intimal flap/dissection. Postoperative status was correlated with intraoperative DUS findings. Ninety-one (59%) examinations performed on 87 patients produced normal findings. Forty-seven (30%) examinations performed on 45 patients showed minor abnormalities consisting of insignificant residual plaque, residual external carotid artery stenoses, small intimal flaps, elevated velocities with no associated anatomic lesion, or an arterial kink. Fourteen patients (9%) had significant findings requiring immediate surgical revision. These consisted of large intimal flaps or dissection in six patients, marked residual plaque and significant stenosis in five patients, thrombus in two patients, and a kink in one patient. Three additional patients ( 2 %) had significant findings but were not revised for various reasons. No significant difference was identified in morbidity or mortality rates between those patients with normal findings, those patients with minor technical defects, and those patients with significant abnormalities undergoing immediate surgical revision. However, two of three patients who had significant abnormalities within the common carotid artery that were not revised suffered perioperative ipsilateral strokes. Intraoperative DUS is a safe and accurate method to assess the technical adequacy of CEA. Intraoperative DUS showed significant lesions in 11% of patients. Identification and immediate repair of significant technical defects may decrease perioperative complication rate and long-term restenosis rate.

The objective of this study was to assess the usefulness of a comparison of clinical failure and restenosis rates of endovascular procedures at 1 year in patients with peripheral arterial disease. The resulting comparison is presented as “clinical failure/restenosis coordinate.” The authors screened 171 papers describing the outcome of lower extremity angioplasty or stent placement. In 20 of them, authors reported detailed outcomes of interest, including baseline demographic measurements, location of arterial occlusive lesions, a measure of restenosis (measured by ankle-brachial indices, ultrasonography, or angiography), and clinical outcomes (mortality, repeat percutaneous transluminal angioplasty, or amputation). An overview of these 20 angioplasty papers was performed. Besides the usual meta-analyses of each end point separately, data were also plotted as coordinates of clinical failure versus restenosis. The clinical failure-to-restenosis coordinate was calculated and reported for percutaneous transluminal angioplasty of the aortoiliac and femoropopliteal distributions. Clinically reported outcomes in the literature were used to calculate the clinical failure/restenosis coordinate. This value was significantly different for various locations of the angioplasty and various baseline angiographic characteristics. A numeric coordinate pair of clinical failure and restenosis is identifiable in patients undergoing endovascular treatment of peripheral arterial disease. The varying coordinates may be important in elucidating the incidence and mechanisms of clinical failure after endovascular treatment. The coordinate reported in this article is hypothesis-generating about mechanisms of endovascular treatment failure. This coordinate is important in determining the role of restenosis in the clinical failure of endovascular therapy of peripheral arterial disease.

Abstract Purpose: To detect insulin-like growth factor-IR (IGF-IR) on circulating tumor cells (CTC) as a biomarker in the clinical development of a monoclonal human antibody, CP-751,871, targeting IGF-IR. Experimental Design: An automated sample preparation and analysis system for enumerating CTCs (CellTracks) was adapted for detecting IGF-IR–positive CTCs with a diagnostic antibody targeting a different IGF-IR epitope to CP-751,871. This assay was used in three phase I trials of CP-751,871 as a single agent or with chemotherapy and was validated using cell lines and blood samples from healthy volunteers and patients with metastatic carcinoma. Results: There was no interference between the analytic and therapeutic antibodies. Eighty patients were enrolled on phase I studies of CP-751,871, with 47 (59%) patients having CTCs detected during the study. Before treatment, 26 patients (33%) had CTCs, with 23 having detectable IGF-IR–positive CTCs. CP-751,871 alone, and CP-751,871 with cytotoxic chemotherapy, decreased CTCs and IGF-IR–positive CTCs; these increased toward the end of the 21-day cycle in some patients, falling again with retreatment. CTCs were commonest in advanced hormone refractory prostate cancer (11 of 20). Detectable IGF-IR expression on CTCs before treatment with CP-751,871 and docetaxel was associated with a higher frequency of prostate-specific antigen decline by >50% (6 of 10 versus 2 of 8 patients). A relationship was observed between sustained decreases in CTC counts and prostate-specific antigen declines by >50%. Conclusions: IGF-IR expression is detectable by immunofluorescence on CTCs. These data support the further evaluation of CTCs in pharmacodynamic studies and patient selection, particularly in advanced prostate cancer.

Abstract The ISCL/EORTC recommends revisions to the Mycosis Fungoides Cooperative Group classification and staging system for cutaneous T-cell lymphoma (CTCL). These revisions are made to incorporate advances related to tumor cell biology and diagnostic techniques as pertains to mycosis fungoides (MF) and Sézary syndrome (SS) since the 1979 publication of the original guidelines, to clarify certain variables that currently impede effective interinstitution and interinvestigator communication and/or the development of standardized clinical trials in MF and SS, and to provide a platform for tracking other variables of potential prognostic significance. Moreover, given the difference in prognosis and clinical characteristics of the non-MF/non-SS subtypes of cutaneous lymphoma, this revision pertains specifically to MF and SS. The evidence supporting the revisions is discussed as well as recommendations for evaluation and staging procedures based on these revisions.

Emerging technologies have greatly expanded our ability to detect, characterize, and treat colorectal cancer. The Coalition of Cancer Cooperative Groups convened a multidisciplinary panel, the Scientific Leadership Council in GI cancer, to discuss and advise on the priorities and opportunities to advance current and future approaches into the clinical arena to impact most rapidly the morbidity and mortality from this disease. The Council's recommendations for research priorities are the result of engagement of community and academic oncologists, patient advocacy groups, and other stakeholders including the pharmaceutical industry and governmental agencies. We detail some key prospects for investigation in the areas of colon cancer detection, prevention, and surgical and medical management. Many are in early or definitive clinical trials, and a focus on rapid accrual is urged. The implementation of biology-directed laboratory investigations, both in association with ongoing clinical trials and as a separate developmental strategy for targeted therapies, is supported as the route to individualized therapy.

Purpose MDX-060 is a human anti-CD30 immunoglobulin (Ig) G1κ monoclonal antibody that inhibits growth of CD30-expressing tumor cells in preclinical models. To determine the safety, maximum-tolerated dose (MTD), and efficacy of MDX-060 in patients with relapsed or refractory CD30+ lymphomas, sequential phase I and II studies were performed. Patients and Methods In the phase I portion, MDX-060 was administered intravenously at doses of 0.1, 1, 5, or 10 mg/kg weekly for 4 weeks to cohorts of three to six patients. Twenty-one patients—16 with Hodgkin's lymphoma (HL), three with anaplastic large-cell lymphoma (ALCL), and two with CD30+ T-cell lymphoma—were enrolled. Because of the lack of a defined MTD or dose-response correlation, the phase II portion was amended to include several dose levels. In the phase II portion, an additional 51 patients, 47 with HL and four with ALCL, were treated at doses of 1, 5, 10, and 15 mg/kg. Results MDX-060 was well tolerated, and an MTD has not been identified. Only 7% of patients experienced grade 3 or 4 treatment-related adverse events. Among the 72 patients treated, clinical responses were observed in six. Twenty-five patients had stable disease, including five who remained free from progression 1 year after treatment. Conclusion MDX-060 was well tolerated at doses up to 15 mg/kg. MDX-060 has limited activity as a single agent, but the minimal toxicity observed and the significant proportion of patients with stable disease suggests that further study of MDX-060 in combination with other therapies is warranted.

Purpose An increasing serum prostate-specific antigen (PSA) level is the initial sign of recurrent prostate cancer among patients treated with radical prostatectomy. Salvage radiation therapy (SRT) may eradicate locally recurrent cancer, but studies to distinguish local from systemic recurrence lack adequate sensitivity and specificity. We developed a nomogram to predict the probability of cancer control at 6 years after SRT for PSA-defined recurrence. Patients and Methods Using multivariable Cox regression analysis, we constructed a model to predict the probability of disease progression after SRT in a multi-institutional cohort of 1,540 patients. Results The 6-year progression-free probability was 32% (95% CI, 28% to 35%) overall. Forty-eight percent (95% CI, 40% to 56%) of patients treated with SRT alone at PSA levels of 0.50 ng/mL or lower were disease free at 6 years, including 41% (95% CI, 31% to 51%) who also had a PSA doubling time of 10 months or less or poorly differentiated (Gleason grade 8 to 10) cancer. Significant variables in the model were PSA level before SRT (P < .001), prostatectomy Gleason grade (P < .001), PSA doubling time (P < .001), surgical margins (P < .001), androgen-deprivation therapy before or during SRT (P < .001), and lymph node metastasis (P = .019). The resultant nomogram was internally validated and had a concordance index of 0.69. Conclusion Nearly half of patients with recurrent prostate cancer after radical prostatectomy have a long-term PSA response to SRT when treatment is administered at the earliest sign of recurrence. The nomogram we developed predicts the outcome of SRT and should prove valuable for medical decision making for patients with a rising PSA level.