Adjuvant capecitabine versus nihil in older patients with node-positive/high-risk node-negative early breast cancer receiving ibandronate - The ICE randomized clinical trial.

AIM OF THE STUDY: Evaluation of the impact of a de-escaleted chemotherapy regimen consisting of capecitabine (Cap) on invasive disease-free survival (iDFS) in patients ≥65 years with node-positive/high-risk node-negative early breast cancer (BC) receiving ibandronate (Ib). METHODS: ICE (Ib with or without Cap in Elderly patients with early breast cancer) was a multicentre phase 3 clinical trial with a 2020 update of long-term follow-up for overall survival enroling node-positive/high-risk node-negative patients ≥65 years with early BC. Patients were randomised to Cap 2000 mg/m² day 1-14 q3w for 6 cycles plus Ib (50 mg p.o. daily or alternatively 6 mg intravenous q4w) or Ib alone for 2 years. Endocrine therapy was recommended for hormone receptor (HR)-positive patients. The primary endpoint was iDFS analysed using Cox proportional hazards regression and log-rank analysis. RESULTS: 1358 (96.4%) of 1409 randomised patients started treatment. 564 (83.4%) completed 6 cycles of Cap. 513 (77.7%) and 516 (78.8%) completed Ib in the Cap+Ib and Ib alone arm, respectively. Median age was 71 (range 64-88) years, 1099 (81%) were HR-positive, 705 (51.9%) node-negative. At a median follow-up of 61.3 months, 5-year iDFS was 78.8% for Cap+Ib versus 75.0% for Ib alone (p = 0.80). Effects were independent of age, nodal, and HR status. The addition of Cap caused significantly higher skin and gastrointestinal toxicity. CONCLUSIONS: The adjuvant combination of Cap+Ib did not show significantly better iDFS than Ib alone in node-positive/high-risk node-negative older BC patients, of whom HR-positive patients were also treated with endocrine therapy. TRIAL REGISTRATION: Study in elderly patients with early breast cancer (ICE), NCT00196859, https://clinicaltrials.gov/ct2/show/NCT00196859?term=NCT00196859.

Avoiding insufficient therapies and overdosing with co-reporting eGFRs (estimated glomerular filtration rate) for personalized drug therapy and improved outcomes - a simulation of the financial benefits.

Patients with impaired renal function are at high risk for morbidity and mortality. Chronic kidney disease (CKD) even in the early stages can be associated with significant side effects of drug therapy, longer length of stay, and high costs. Correct assessment of renal function in the hospital is important to detect CKD, to avoid further damage to the kidneys, and to optimize pharmacological therapy. Current protocols for renal function testing in drug dosing are only creatinine based, are not robust enough, and can wrongly classify certain patients. Goal of our simulation study is to optimize noninvasive renal function estimates and to allow for optimal dosing of pharmacological treatment without further renal damage. Co-reporting of creatinine- and of cystatin C-derived estimated glomerular filtration rates (eGFR) allows a personalized approach for patients with large discrepancies in eGFR and it enabled us in detecting patients at high risk for side effects due to incorrect drug dosing. This approach might be highly effective for patients as well as for clinicians. In addition, we simulated the efficiency by estimating savings for the hospital administration and the payor with a benefit cost ratio of 58 to 1.

Gene Expression-Based Prediction of Neoadjuvant Chemotherapy Response in Early Breast Cancer: Results of the Prospective Multicenter EXPRESSION Trial.

PURPOSE: Expression-based classifiers to predict pathologic complete response (pCR) after neoadjuvant chemotherapy (NACT) are not routinely used in the clinic. We aimed to build and validate a classifier for pCR after NACT. PATIENTS AND METHODS: We performed a prospective multicenter study (EXPRESSION) including 114 patients treated with anthracycline/taxane-based NACT. Pretreatment core needle biopsies from 91 patients were used for gene expression analysis and classifier construction, followed by validation in five external cohorts (n = 619). RESULTS: A 20-gene classifier established in the EXPRESSION cohort using a Youden index-based cut-off point predicted pCR in the validation cohorts with an accuracy, AUC, negative predictive value (NPV), positive predictive value, sensitivity, and specificity of 0.811, 0.768, 0.829, 0.587, 0.216, and 0.962, respectively. Alternatively, aiming for a high NPV by defining the cut-off point for classification based on the complete responder with the lowest predicted probability of pCR in the EXPRESSION cohort led to an NPV of 0.960 upon external validation. With this extreme-low cut-off point, a recommendation to not treat with anthracycline/taxane-based NACT would be possible for 121 of 619 unselected patients (19.5%) and 112 of 322 patients with luminal breast cancer (34.8%). The analysis of the molecular subtypes showed that the identification of patients who do not achieve a pCR by the 20-gene classifier was particularly relevant in luminal breast cancer. CONCLUSIONS: The novel 20-gene classifier reliably identifies patients who do not achieve a pCR in about one third of luminal breast cancers in both the EXPRESSION and combined validation cohorts.

Physical basis of the 'magnification rule' for standardized Immunohistochemical scoring of HER2 in breast and gastric cancer.

BACKGROUND: Detection of HER2/neu receptor overexpression and/or amplification is a prerequisite for efficient anti-HER2 treatment of breast and gastric carcinomas. Immunohistochemistry (IHC) of the HER2 protein is the most common screening test, thus precise and reproducible IHC-scoring is of utmost importance. Interobserver variance still is a problem; in particular in gastric carcinomas the reliable differentiation of IHC scores 2+ and 1+ is challenging. Herein we describe the physical basis of what we called the 'magnification rule': Different microscope objectives are employed to reproducibly subdivide the continuous spectrum of IHC staining intensities into distinct categories (1+, 2+, 3+). METHODS: HER2-IHC was performed on 120 breast cancer biopsy specimens (n = 40 per category). Width and color-intensity of membranous DAB chromogen precipitates were measured by whole-slide scanning and digital morphometry. Image-analysis data were related to semi-quantitative manual scoring according to the magnification rule and to the optical properties of the employed microscope objectives. RESULTS: The semi-quantitative manual HER2-IHC scores are correlated to color-intensity measured by image-analysis and to the width of DAB-precipitates. The mean widths ±standard deviations of precipitates were: IHC-score 1+, 0.64 ± 0.1 µm; score 2+, 1.0 ± 0.23 µm; score 3+, 2.14 ± 0.4 µm. The width of precipitates per category matched the optical resolution of the employed microscope objective lenses: Approximately 0.4 µm (40×), 1.0 µm (10×) and 2.0 µm (5×). CONCLUSIONS: Perceived intensity, width of the DAB chromogen precipitate, and absolute color-intensity determined by image-analysis are linked. These interrelations form the physical basis of the 'magnification rule': 2+ precipitates are too narrow to be observed with 5× microscope objectives, 1+ precipitates are too narrow for 10× objectives. Thus, the rule uses the optical resolution windows of standard diagnostic microscope objectives to derive the width of the DAB-precipitates. The width is in turn correlated with color-intensity. Hereby, the more or less subjective estimation of IHC scores based only on the staining-intensity is replaced by a quasi-morphometric measurement. The principle seems universally applicable to immunohistochemical stainings of membrane-bound biomarkers that require an intensity-dependent scoring.

3D Printing Gets a Boost and Opportunities with Polymer Materials.

3D printing has recently gained much attention from media and the scientific community, touted as a replacement for traditional manufacturing and a potential to change the way we develop, produce, market, and distribute all sorts of products. With a short introduction to the general idea and initial development of rapid prototyping, we have a look at the prevalent technologies which are now summarized as 3D printing, each with its specific properties and reliance on the materials adapted to the automated application process. Polymers in various forms, reactive, liquid solutions, or as thermoplastic melts, play a key role in many applications and the further expansion toward manufacturing robust, real end use products.

Reinforcement of stereolithographic resins for rapid prototyping with cellulose nanocrystals.

We report on the mechanical properties of optically curable stereolithographic resins (SLRs) which were reinforced through the addition of small amounts of cellulose nanocrystals (CNCs). The resin/filler mixtures are readily accessible via simple mixing processes. A detailed rheological investigation of such mixtures and the successful processing of these materials on a commercial SLR machine show that at low filler concentrations (below 5%) the processability of the materials is barely impacted. The storage modulus, E', increased steadily with increasing CNC content in the regimes below and above the glass transition. A remarkable modulus enhancement was observed in the rubbery regime, where E' increased by 166, 233, and 587% for CNC/SLR nanocomposites with 0.5, 1.0, and 5.0% w/w CNC, respectively. The modulus increase was less pronounced in the glassy state, where E' increased by 21, 32 and 57%, for the same compositions. The increase in tensile strength was of similar magnitude. In comparison to previously reported CNC and carbon-nanofiller based nanocomposites, the presently investigated nanocomposites display a comparably large increase of stiffness and strength, which appear to originate from the high level of dispersion and the intimate contact of the CNCs with the SLR matrix. Through the fabrication of 3-dimensional parts, it was shown that the CNC-filled resins can be processed with standard equipment in a stereolithographic process that is widely used for rapid prototyping and rapid manufacturing.

HER2 testing in gastric cancer: a practical approach.

Trastuzumab in combination with capecitabine or 5-fluorouracil and cisplatin is approved by the European Medicines Agency for the treatment of patients with human epidermal growth factor receptor 2 (HER2)-positive (immunohistochemistry 3+ or immunohistochemistry 2+/fluorescence in situ hybridization-positive or immunohistochemistry 2+/silver in situ hybridization-positive) metastatic adenocarcinoma of the stomach or gastro-esophageal junction. Approvals are underway in other countries, with recent approvals granted in the United States and Japan. Experience and data from trastuzumab use in breast cancer have highlighted the importance of quality HER2 testing and scoring to ensure accurate identification of patients eligible for treatment. HER2 testing in gastric cancer differs from testing in breast cancer due to inherent differences in tumor biology; gastric cancer more frequently shows HER2 heterogeneity (focal staining) and incomplete membrane staining. Consequently, gastric cancer-specific HER2 testing protocols have been developed and standardized and it is imperative that these recommendations be adhered to. Given the predictive value of HER2 protein levels with response in the trastuzumab for GAstric cancer study (ToGA), immunohistochemistry should be the initial testing methodology and fluorescence in situ hybridization or silver in situ hybridization should be used to retest immunohistochemistry 2+ samples. Wherever possible, bright-field methodologies should be used as these are considered to be superior to fluorescent methodologies at identifying heterogeneous staining. Specific training is required before embarking on HER2 testing in gastric cancer, irrespective of the experience of HER2 testing in breast cancer. This paper provides the most up-to-date practical guidance on HER2 testing and scoring in patients with gastric and gastro-esophageal junction cancer, as agreed by a panel of expert pathologists with extensive experience of HER2 testing particularly reflecting the European Medicines Agency-approved indication. It is anticipated that these recommendations should ensure accurate and consistent HER2 testing, which will allow appropriate selection of patients eligible for treatment with trastuzumab.

Chromogenic in situ hybridisation for the assessment of HER2 status in breast cancer: an international validation ring study.

INTRODUCTION: Before any new methodology can be introduced into the routine diagnostic setting it must be technically validated against the established standards. To this end, a ring study involving five international pathology laboratories was initiated to validate chromogenic in situ hybridisation (CISH) against fluorescence in situ hybridisation (FISH) and immunohistochemistry (IHC) as a test for assessing human epidermal growth factor receptor 2 (HER2) status in breast cancer. METHODS: Each laboratory performed CISH, FISH and IHC on its own samples. Unstained sections from each case were also sent to another participating laboratory for blinded retesting by CISH ('outside CISH'). RESULTS: A total of 211 invasive breast carcinoma cases were tested. In 76 cases with high amplification (HER2/CEP17 ratio >4.0) by FISH, 73 cases (96%) scored positive (scores >or= 6) by 'outside CISH'. For FISH-negative cases (HER2/CEP17 ratio <2.0), 94 of 100 cases (94%) had CISH scores indicating no amplification (score or= 6. CISH intra-laboratory concordance with IHC was 92% for IHC-negative cases (IHC 0/1+) and 91% for IHC 3+ cases. Among IHC 2+ cases, CISH was 100% concordant with samples showing high amplification by FISH, and 94% concordant with FISH-negative samples. CONCLUSION: These results show that CISH inter- and intra-laboratory concordance to FISH and IHC is very high, even in equivocal IHC 2+ cases. Therefore, we conclude that CISH is a methodology that is a viable alternative to FISH in the HER2 testing algorithm.

Four-year results after brachytherapy for diffuse coronary in-stent restenosis: will coronary radiation therapy survive?

BACKGROUND: Prior to the introduction of drug-eluting stents (DES), diffuse coronary in-stent restenosis (ISR) was mainly treated by brachytherapy (BT), with good short-term and mid-term results. However, there exist limited data on the long-term effects of BT that justify its continuous use. MATERIALS AND METHODS: Two hundred patients with diffuse ISR treated with intravascular BT were retrospectively followed over 4 years. Group A (n=134) was treated with the noncentered (90)Sr/Y BetaCath radiation system, whereas Group B (n=66) was treated with the centered 32P Galileo source wire system. Primary endpoints after 4 years were target lesion restenosis (TLS) and target lesion revascularization (TLR). Secondary endpoints were target vessel revascularization (TVR) and nontarget vessel revascularization (NTVR), as well as major adverse cardiac events (MACE). RESULTS: Follow-up at 4 years yielded a TLS rate of 37.6% (Group A, 40.8%; Group B, 31.1%; P=.48). TLR was performed in 34.8% of patients (37.5% in Group A vs. 29.5% in Group B; P=.55). Ten percent of patients underwent coronary bypass surgery. Percutaneous coronary intervention was performed more often in Group A (27.5%) than in Group B (19.7%), while TVR was less frequent in Group A (10.0%) than in Group B (18.0%). NTVR was undertaken in 25.0% of Group A patients versus 21.3% of Group B patients, and MACE occurred in 1.7% of Group A patients versus 3.3% of Group B patients. These differences were not statistically significant (P>.05). CONCLUSIONS: While excellent short-term and mid-term results after coronary BT are widely accepted, a high TLS rate can be observed after 4 years. The potential superiority of DES to BT will depend on the availability of long-term clinical data.

Initial clinical experience with the Protégé EverFlex long self-expanding nitinol stent in the superficial femoral artery.

AIMS: Clinical results following stent implantation in the superficial femoral artery (SFA) are limited due to restenosis, often caused by stent fractures. Therefore new stent devices are desirable. The present study details our initial experience with the routine use of the novel Protégé EverFlex long self-expanding nitinol stent for treatment of long SFA total occlusions or stenoses. METHODS AND RESULTS: Between February and March 2006 a total of 15 EverFlex nitinol stents were implanted in 12 patients with either total SFA occlusions (n = 9) or long stenoses (n = 3), mean lesion length 14.9 cm (+/- 10.4 cm). All patients presented with claudication stage Fontaine IIb (Rutherford category 3). Stent lengths were 10 cm (n = 6), 12 cm (n = 1), or 15 cm (n = 8), stent diameters were 6 mm (n = 14) and 7 mm (n = 1). Access was gained either by the crossover (n = 9), antegrade (n = 2), or popliteal approach (n = 1). After predilatation, stent placement and postdilatation were performed with 100% technical success. Clinical and apparative follow-up after 6-8 weeks indicated the absence of restenosis or reocclusion in all cases. CONCLUSION: The novel long self-expanding EverFlex nitinol stent (10 cm/12 cm/15 cm in length) exhibits excellent technical handling characteristics with good short-term clinical results. Mid-term and long-term clinical results as well as potential stent fractures need to be further examined.

One-year clinical outcomes after complete arterial coronary revascularization.

BACKGROUND: Conventional coronary bypass surgery applies single internal mammary arteries and saphenous vein graft conduits for revascularization of occluded coronary arteries. While the use of saphenous vein grafts is limited by early graft occlusion, little data exist on clinical experiences with complete arterial revascularization. PATIENTS AND METHOD: From January 2003 to July 2004, 390 patients were transferred from Red Cross Hospital Cardiology Center to the Rotenburg Cardiovascular Center for coronary bypass operation. From these patients, 200 were selected for complete arterial revascularization. Mean age of the patients was 66.7+/- 8.0 years; 80.5% were male; 68.5% had triple-vessel disease, 31% had two-vessel disease, and 0.5% had single-vessel disease; 32% were diabetic; and 6.5% had a previous bypass operation. Left ventricular ejection fraction was >50% in 85.5% and 30-50% in 14.5%. Double internal mammary artery grafts were used in 98% and single internal mammary artery grafts in 2%. In 51%, the right internal mammary artery was connected with the left internal mammary artery as a T-graft and in 17%, it was used as a free aortocoronary graft. Radial artery grafts were used in 4%. The average number of anastomoses per patient was 3.4. RESULTS: During the primary in-hospital stay, 1.5% of the patients had to undergo reoperation, 3.5% had myocardial infarctions, 3.5% had wound healing complications, 1.0% experienced an ischemic stroke, and 1 patient died following an acute myocardial infarction. At 12 months, 1.0% underwent percutaneous reinterventions, 0.5% had to be reoperated, 0.5% had a myocardial infarction, and 1.0% died. The actuarial survival rate at 12 months was 99%. CONCLUSION: When both the internal mammary arteries are used as the preferred surgical strategy, complete arterial revascularization can be performed with excellent clinical results over 12 months.

Percutaneous saphenous vein graft interventions with and without distal filter wire protection.

BACKGROUND: Embolic protection during SVG interventions using distal balloon occlusion and aspiration has shown to reduce periprocedural complications compared to unprotected SVG interventions. A similar effect is expected from filter wires. PATIENTS AND METHODS: A total of 174 SVG interventions carried out with (group A; n=87) or without distal filter wire protection (group B; n=87) were retrospectively matched for the location of distal graft anastomosis and analyzed for baseline and procedural characteristics, for TIMI flow grade before and after PCI, for the post-procedural CK elevation, and for major adverse cardiac events at 30 days and 6 months (primary end point). Location of distal graft anastomosis was the left anterior descending artery in 19.6%, the left diagonal branch in 6.9%, the left marginal branch in 17.2%, the left posterolateral branch in 24.2%, the mid-segment of the right coronary artery in 28.7%, and the posterior descending artery in 3.4%. RESULTS: Baseline clinical demographics showed no relevant differences between both the groups. Mean age of vein grafts was 11.7+/- 4.3 years in group A versus 10.6+/- 4.9 years in group B (P=0.15). The number of stents per lesion was 1.4+/- 0.8 in group A versus 1.0+/- 0.8 in group B (P<0.01). The total length of stents was 32.2+/- 16.2 mm in group A versus 20.9+/-12.1 mm in group B (P<0.01). TIMI flow grade pre was 2.5+/-0.8 in group A versus 2.7+/- 0.6 in group B (P<0.05). TIMI flow grade post was 2.9+/- 0.3 versus 2.9+/- 0.2. Improvement of TIMI flow grade after SVG intervention was 0.4+/- 0.7 in group A versus 0.2+/- 0.6 in group B (P<0.05). Post-procedural CK-MB elevations were observed in 17 patients of group A versus 14 patients of group B (P=0.18). At 30 days, there were no myocardial infarctions (MIs) and no deaths in either group. One patient of group A had to be reoperated and four patients of group A underwent repeat PCI (4.6%) versus one patient of group B (1.2%). At 6 months, there were again no MIs and no deaths in either group. Target lesion revascularization rate was 17.3% in group A versus 11.5% in group B (P <0.02). CONCLUSION: When distal filter wire protection is used in high risk SVG lesions, the clinical outcome of percutaneous interventions may be equal to low risk SVG lesions without filter wire protection.

Comparison of a centered 32P source wire system with a noncentered 90Sr/Y brachytherapy system for intracoronary beta-radiation following PCI of diffuse in-stent restenosis.

BACKGROUND: We investigated the potential impact of differences in effective radiation dose between the centered Guidant 32P source wire system and the noncentered Novoste 90Sr/Y BetaCath system on clinical and angiographic outcomes of intracoronary brachytherapy for the prevention of in-stent restenosis. METHODS: From 10/00 to 05/04, a total of 400 patients underwent percutaneous coronary intervention (PCI) with brachytherapy for diffuse in-stent restenosis at our institution. Following balloon dilatation, patient Group A (n=200) was treated with the centered 32P Galileo source wire system, patient Group B (n=200) was treated with the noncentered 90Sr/Y BetaCath radiation system. In Group A, the prescribed dose of 20 Gy was applied in 1-mm depth of the vessel wall. In Group B, the prescribed dose of 18.4 Gy was applied for visual reference vessel sizes >2.7 and <3.35 mm, 23 Gy for >3.36 and <4.00 mm, and 25.3 Gy for >4.00 mm, each calculated at a distance of 2 mm from the center line of the radiation source. Patients received aspirin and clopidogrel over 12 months. Primary endpoint was target lesion revascularization (TLR) at 6 months. Secondary endpoints were the binary restenosis rate and major adverse cardiac event (MACE) at 30 days and 6 months. RESULTS: At 30 days, one patient of each group underwent PCI at a nontarget lesion (0.5%). At 6 months, MACEs were equally distributed in both groups. Target lesion revascularization at 6 months was 5.9% in Group A and 9.2% in Group B (P=.08). Binary angiographic restenosis rate at 6 months was 5.5% in Group A and 11.2% in Group B (P=.014). CONCLUSION: Intracoronary beta-radiation using the centered 32P source wire system yielded a significant reduction of recurrence rate compared to the noncentered 90S/Y BetaCath system after PCI of diffuse in-stent restenosis. There was a nonsignificant trend toward reduction of TLR among patients treated with the centered 32P source wire system.

Relationship between size of myocardial infarctions assessed by delayed contrast-enhanced MRI after primary PCI, biochemical markers, and time to intervention.

BACKGROUND: The quantitative assessment of myocardial infarctions using delayed contrast-enhanced magnetic resonance imaging (MRI) has recently been validated using postmortem histopathological animal studies. In a prospective study, we investigated the correlation between infarct size as assessed by delayed contrast-enhanced MRI, elevation of creatine kinase (CK), and c-reactive protein (CRP) as well as the time from onset of symptoms to intervention. METHODS: Four to 10 days after immediate PCI in 45 acute ST-segment elevation myocardial infarction (STEMI) patients (<24 hour) with stenting of the infarct-related artery and treatment with abciximab, we performed gadolinium contrast-enhanced three-dimensional inversion recovery gradient-echo MR sequences with complete coverage of the LV-myocardium in short-axis slices. The mass of infarcted tissue based on the volume of hyperenhanced myocardium was calculated and linear regression analysis was performed to assess the correlation between absolute size of infarctions (g) as well as relative size (LV%) with peak values of CK, CRP, and the time to PCI. RESULTS: There was a significant correlation between absolute size of infarctions (g) and peak CK values (r = 0.72; P < 0.001) as well as the relative size (LV%) and peak CK (r = 0.77; P < 0.001). No correlations were found between absolute size (r = 0.33) as well as relative size (r = 0.27) of infarctions and peak CRP. There was also no correlation between absolute (r = 0.29) as well as relative size of infarctions (r = 0.27) and the time from onset of symptoms to PCI. CONCLUSIONS: In patients with acute STEMI (<24 hour) undergoing immediate PCI with stenting and treatment with abciximab, peak CK values correlated well with infarct size as assessed by delayed contrast-enhanced MRI. There were no correlations between infarct size and peak CRP as well as the time to intervention.

Clinical experiences using everolimus-eluting stents in patients with coronary artery disease.

Despite the growing use of drug-eluting stents, restenosis remains to occur especially in high risk subgroups like patients with diffuse in-stent restenosis. This observation is supporting the search for new and potentially even more effective drug eluting stent systems. Everolimus has been used in conjunction with a new bioabsorbable polymer and gave promising results in initial clinical studies. In FUTURE I, a single-center, single-blinded randomized safety and feasibility study enrolling 15 patients with bare metal stents and 27 patients with everolimus-coated stents, 30-day MACE rate was 0% in both groups. In-stent late loss at six months was 0.83 mm in the control group and 0.10 mm in the everolimus group (p < 0.0001). In FUTURE II, a randomized multi-center study, a total of 64 patients were enrolled confirming safety and feasibility. After 6 months late loss was 0.85 mm in the control group and 0.12 mm in the everolimus group (p < 0.001).

Endovascular interventions in iliac and infrainguinal occlusive artery disease.

Percutaneous endovascular procedures are increasingly applied to treat symptomatic peripheral occlusive artery disease. While the primary technical success and recanalization rates in iliac and infrainguinal interventions are high, differences in the long-term patency rates exist with respect to the anatomic localization, separating the iliac, femoropopliteal, and infrapopliteal arterial regions. In iliac arteries, even complex lesions can be recanalized with good long-term patency rates, especially when using self-expanding nitinol stents. In the infrainguinal arteries the method of choice is still under debate (e.g., balloon angioplasty vs stent implantation). A high restenosis rate represents one of the major limitations in femoropopliteal and infrapopliteal interventions. Therefore, additional methods and treatment strategies for peripheral interventions with the potential for future applications are under investigation and will be discussed such as drug-eluting stents, brachytherapy, subintimal angioplasty, laser angioplasty, atherectomy/thrombectomy, cutting balloon, polytetrafluoroethylene (PTFE)-covered stent grafts, biodegradable stents, and cryoplasty. The increasing amount of data on successful peripheral interventions supports the necessity to adapt and reevaluate the current consensus guidelines that were put together in 2000.

Long-term outcome after implantation of bare metal stents for the treatment of coronary artery disease: rationale for the clinical use of antiproliferative stent coatings.

BACKGROUND: The widespread use of drug-eluting stents in patients with coronary artery disease (CAD) is hampered by unequal regulations for reimbursement. Identification of patients with maximal benefit from this technology may be achieved by assessing long-term clinical outcome after implantation of uncoated bare metal stents. PATIENTS AND METHODS: A consecutive series of 1,000 patients with CAD treated with bare metal coronary stents of various designs from January 1995 to December 1995 was retrospectively followed over 4 years. The primary end points of the study were major adverse cardiac events. RESULTS: The mean age of patients was 62 +/- 10.3 years, 77.5% were male, and 18% were diabetic. Clinical follow-up was obtained in 821 patients (82.1%) after 4.6 +/- 1.1 years. During this period of time, 31.8% were admitted for repeat PCI, 15.1% underwent CABG operation, 3.5% had myocardial infarctions, and 3.7% died. At 4 years, 46.3% of diabetic patients survived without event versus 57.6% of nondiabetic patients (P < 0.05). Patients with CAD I survived without event in 65.3% versus 54.0% of patients with CAD II and 48.5% of patients with CAD III (P < 0.02). CONCLUSION: Implantation of uncoated stents provides the worst long-term clinical outcome in patients with diabetes and those with multivessel CAD. Both groups of patients appear to be primary candidates for the use of drug-eluting stents.

Comparison of stainless steel stents coated with turbostratic carbon and uncoated stents for percutaneous coronary interventions.

BACKGROUND: Stent coating with turbostratic carbon was supposed to minimize the local inflammatory response after stent implantation and to thereby also reduce the rates of restenosis and clinical events. METHODS AND RESULTS: From October, 1999 to February, 2002, a total of 329 patients with symptomatic coronary artery disease (CAD) eligible for single-lesion PCI were randomized for implantation of either a CarboStent (C; n = 168) or a stainless-steel stent (S; n = 161). The stainless-steel stents were Tristar stents in 60.2%, Tetra stents in 17.4% and Penta stents in 22.4%. Both groups showed no differences in baseline clinical and angiographic characteristics. Angiographic follow-up (FU) was obtained after 6 months in 287 patients (87.2%), clinical FU in 295 patients (89.7%). With the exception of a smaller post-procedure minimal luminal diameter (MLD) in the C group (2.59 0.43 mm versus 2.72 0.46 mm in the S group; p = 0.01), there were no significant differences between the C and S groups in lesion length (10.28 4.45 mm versus 10.37 4.79 mm, respectively), reference diameter (2.92 0.59 mm versus 2.89 0.53 mm, respectively), pre-procedure MLD (0.77 0.36 mm versus 0.84 0.36 mm, respectively), MLD at FU (1.67 0.64 mm versus 1.68 0.57 mm, respectively), late loss (0.93 0.63 mm versus 1.05 0.59 mm, respectively), late loss index (0.51 0.32 versus 0.57 0.32, respectively) and restenosis rate (18.1% versus 20.6%, respectively). There were also no significant differences regarding major adverse cardiac events (MACE) between the C and S groups, i.e., occurrence of death (0% versus 0.7%, respectively), myocardial infarction (0% versus 0.7%, respectively), coronary artery bypass graft (0.7% versus 1.4%, respectively) and target lesion revascularization (16.4% versus 21.5%, respectively). CONCLUSION: Coronary stents coated with turbostratic carbon gave no clinically relevant reduction of in-stent restenosis and MACE rates when compared to uncoated stents.

mRNA detection of tumor-rejection genes BAGE, GAGE, and MAGE in peritoneal fluid from patients with ovarian carcinoma as a potential diagnostic tool.

BACKGROUND: It has been found that the members of the BAGE, MAGE, and GAGE gene families are expressed almost exclusively in neoplastic tissues. Normal tissues, except testis and placenta, are negative. Therefore, the expression of these genes may serve as a useful diagnostic marker in detecting malignant disease. The involvement of the serous cavities by malignant neoplasms has important therapeutic and prognostic implications. Accordingly, the diagnosis of peritoneal spread of ovarian carcinoma plays an important role for both initial and second-look staging procedures. In some patients, however, a definite diagnosis cannot be established by morphologic or immunocytologic examination alone. Detection of tumor specific gene expression may be a sensitive additional tool in these settings. METHODS: The authors studied the gene expression observed in 44 ascites specimens. Gene expression was evaluated by reverse transcription-polymerase chain reaction analysis and sequencing. RESULTS: Of 44 ascites specimens, the expression of BAGE, MAGE-1, MAGE-3, and GAGE-1/2 was recognized in 17 specimens (63%), 2 specimens (7%), 8 specimens (30%), and 8 specimens (30%) with histologically proven ovarian carcinoma, respectively. Expression of the MAGE and GAGE genes was not observed in patients with nonneoplastic disease, whereas BAGE expression was seen in one patient with cirrhosis. CONCLUSIONS: These findings show that testing for BAGE, GAGE-1/2, MAGE-1, and MAGE-3 transcriptional activity in ascites specimens results in high sensitivity in diagnosing malignant ascites.

Fine needle aspiration of the thyroid: can an image processing system improve differentiation?

OBJECTIVE: To differentiate thyroid nodules by means of fine needle aspiration with subsequent computer-aided diagnosis. STUDY DESIGN: Fine needle aspiration biopsies obtained from 137 patients for whom histopathologic diagnosis was available were investigated: 16 hyperplastic nodules (12%), 39 adenomas (28%), 25 follicular thyroid carcinomas (18%), 19 follicular variants of papillary thyroid carcinoma (14%) and 38 papillary thyroid carcinomas (28%). From each stained specimen 100 cell scenes were scanned and analyzed, constituting a total of 62,325 cell images. RESULTS: All the entities described could be well discriminated from each other by automated image analysis methods. Both the diagnosis of tumor type and the differentiation between benign and malignant could be achieved with a sensitivity of .98. CONCLUSION: With only 7-10 calculated cell features (texture line analysis) and classification with decision trees, a tool for high-quality cell image diagnosis is available. Subtypes of cells characterized by the calculated features could be found in all the specimens and could be assigned to the malignancies with high statistical significance. The method increases the relevance of image processing as an additional diagnostic tool for cytologic examination of thyroid nodules.