Ultrasound-guided lymph node sampling: accuracy of FNAC, end-cutting (Franseen), and side-cutting (Temno) needle biopsy techniques.

AIM: To compare technical success, diagnostic accuracy, and histological yield of fine-needle aspiration cytology (FNAC), side-cutting (Temno) needle biopsy, and end-cutting (Franseen) needle biopsy for ultrasound-guided sampling of groin and axillary lymph nodes. MATERIALS AND METHODS: A total of 270 abnormal groin and axillary nodes were sampled using one of the three techniques. Nodes with a maximum length of <2.5 cm underwent FNAC or Franseen biopsy, while nodes >2.5 cm underwent Temno biopsy. Mean size of nodes sampled by FNAC (21.2 mm) and Franseen (19.7 mm) were similar while nodes sampled by Temno were larger (34.4 mm, p<0.0001). RESULTS: Technical success rates of FNAC (82/93, 88%), Franseen (105/111, 95%), and Temno (59/66, 89%) biopsies were similar (p>0.05 for all). Lymphoid tissue yield by FNAC (mean total area 1.51 mm2) was less than that by Franseen (7.14 mm2, p=0.002) or Temno biopsy (19.44 mm2, p<0.0001). Diagnostic accuracy for malignancy was lower for FNAC (22/30, 73%) than Franseen (25/26, 96%, p=0.02) or Temno biopsy (32/32, 100%, p=0.002). For malignant nodes, determining the likely organ of origin was also lower for FNAC (7/30, 23%) than Franseen (19/26, 73%, p=0.0002) or Temno biopsy (29/32, 91%, p<0.0001), with a similar pattern observed in the identification of lymphoma. CONCLUSION: For similarly sized nodes, Franseen biopsy provided more lymphoid material, a higher diagnostic accuracy for malignancy including lymphoma, and better identification of the likely organ of origin than FNAC. Routine use of Franseen biopsy is advocated rather than FNAC for percutaneous sampling of lymph nodes not suitable for side-cutting needle biopsy.

PET/CT Is Complementary to Fine-Needle Aspiration Cytology in Assessment of Irradiated Neck in Head and Neck Cancers.

Background. Accurate assessment of irradiated neck in squamous cell carcinoma of the head and neck (HNSCC) is essential. Fine-needle aspiration cytology is often performed for suspicious lesions but it is limited by its low negative predictive value (NPV). We postulated that F-18 fluorodeoxyglucose (FDG) positron emission tomography combined with computed tomography (PET/CT) can overcome this limitation by its high NPV value and allow for a more accurate assessment of irradiated neck in HNSCC. Methods. Fifty-four HNSCC patients were included for the study. They all received previous irradiation to the neck. Clinical characteristics, details of radiotherapy, PET/CT results, follow-up findings, and final histological diagnosis were analyzed. Results. The sensitivity, specificity, positive predictive value (PPV), and NPV were 95.8%, 96.7%, 95.8%, and 96.7%, respectively. Age, sex, radiation dose, interval between PET/CT and radiotherapy completion, nature of radiotherapy, and use of second course of radiotherapy were not found to affect diagnostic accuracy of PET/CT. A new algorithm for investigation of masses in irradiated neck is proposed. Conclusions. PET/CT is an effective diagnostic tool and has a complementary role to FNAC in the management of irradiated neck in head and neck cancers, particularly in cases where suspicious lesions were identified but FNAC showed negative results.

Deltopectoral flap in the era of microsurgery.

Background. Our study aimed to review the role of deltopectoral (DP) flap as a reconstructive option for defects in the head and neck region in the microvascular era. Methods. All patients who received DP flap reconstruction surgery at the Department of Surgery, Queen Mary Hospital, between 1999 and 2011 were recruited. Demographic data, indications for surgery, defect for reconstruction, and surgical outcomes were analyzed. Results. Fifty-four patients were included. All but two patients were operated for reconstruction after tumour resection. The remaining two patients were operated for necrotizing fasciitis and osteoradionecrosis. The majority of DP flaps were used to cover neck skin defect (63.0%). Other reconstructed defects included posterior pharyngeal wall (22.2%), facial skin defect (11.1%), and tracheal wall (3.7%). All donor sites were covered with partial thickness skin graft. Two patients developed partial flap necrosis at the tip and were managed conservatively. The overall flap survival rate was 96.3%. Conclusions. Albeit the technical advancements in microvascular surgery, DP still possesses multiple advantages (technical simplicity, reliable axial blood supply, large size, thinness, and pliability) which allows it to remain as a useful, reliable, and versatile surgical option for head and neck reconstruction.

Predictors of restenosis after carotid endarterectomy: 17-year experience in a tertiary referral vascular center.

INTRODUCTION: Carotid endarterectomy (CEA) is a well-established surgical technique in stroke prophylaxis. Long-term follow-up data on restenosis or recurrent neurological symptoms in Oriental patients are unclear. METHODS: Patients' notes from 1994 to 2011 were retrospectively reviewed and analyzed. A total of 301 cases of CEA were identified. RESULTS: A lower restenosis rate was associated with the use of patch and never smokers in both univariate and multivariate analysis. Use of patch and never smokers were also found to be significantly associated with longer restenosis-free survival. Use of patch and postoperative use of statin were associated with better overall survival in both univariate and multivariate analysis. CONCLUSION: Use of patch and lack of smoking history are associated with less restenosis and longer restenosis-free survival. Use of patch and use of postoperative statin improves overall survival. Although restenosis after CEA is relatively common, reintervention was rarely necessary.

Risk of osteonecrosis in patients taking bisphosphonates for prevention of osteoporosis: a systematic review and meta-analysis.

SUMMARY: We aimed to systematically review observational studies evaluating use of bisphosphonates (BPs) and risk of osteonecrosis of jaw (ONJ) or other sites among non-cancer patients. INTRODUCTION: PubMed, EMBASE, and Cochrane Library were screened from database inception to Dec 2012. METHODS: Two reviewers independently identified cohort and case-control studies evaluating the use of oral or intravenous (IV) BPs and the risk of ONJ and extracted the characteristics of the studies and risk estimates. Pooled estimates of odds ratios and 95 % confidence intervals (CI) were derived by random effects meta-analysis. Subgroup analyses were carried according to patients' characteristics and route of BP use. RESULTS: We identified 12 studies, including 2,652 cases and 1,571,997 controls. Use of BPs was associated with a significantly increased risk of ONJ or ON of other sites [odds ratio (OR) 2.32; 95 % CI 1.38-3.91; I (2) = 91 %]. The summary OR was 2.91 (95 % CI 1.62-5.22; I (2) = 85.9 %) for adjusted studies. Use of BPs were associated with higher risk on ONJ (OR 2.57; 95 % CI 1.37-4.84; I (2) = 92.2 %) than ON of other sites (OR 1.79; 95 % CI 0.71-4.47; I (2) = 83.3 %). Meta-regression analysis did not find design characteristics or outcome definitions to be significant sources of heterogeneity. CONCLUSION: The available evidence suggests that use of BPs in cancer patients is associated with a substantial risk for ONJ. Patients receiving IV BP are at highest risk.

Effects of unilateral internal jugular vein removal on intraocular pressure.

PURPOSE: To investigate the intraocular pressure (IOP) and retinal nerve fibre layer (RNFL) thickness after ipsilateral neck dissection with internal jugular vein (IJV) removal for head and neck tumours. METHODS: A computer search was performed to identify all patients who were treated with neck dissection with unilateral IJV removal from 2005 to 2012. All patients underwent a complete ophthalmological examination including measurement of IOP by Goldmann applanation tonometry and the average RNFL thickness using a Spectralis optical coherence tomography. The following analyses were made between the eyes on the side of the IJV removal versus the eye on the contralateral side: gonioscopy, IOP, vertical cup-disc ratio (VCDR) and peripapillary RNFL. Correlation analysis between the year of operation and IOP was done using the Pearson correlation coefficient. RESULTS: This prospective cross-sectional study recruited 38 patients. The median age at operation was 59.5 years (range 33-87 years). There were 26 males and 12 females. Exactly half of the patients had left IJV removal and the remaining half had right IJV removal. The median interval from neck dissection to eye assessment was 46.5 months (range 11-97 months). There was no significant difference between the ipsilateral and contralateral side in terms of gonioscopy, IOP, VCDR, and RNFL. There was no significant correlation between the duration of IJV removal and IOP (p=0.8). CONCLUSIONS: Ipsilateral IJV removal after neck dissection did not result in any significant differences in the average peripapillary RNFL thickness or IOP compared to the contralateral eye at a mean of 46.5 months postoperatively.

BDNF and TNF-α polymorphisms in memory.

Here, we investigate the genetic basis of human memory in healthy individuals and the potential role of two polymorphisms, previously implicated in memory function. We have explored aspects of retrospective and prospective memory including semantic, short term, working and long-term memory in conjunction with brain derived neurotrophic factor (BDNF) and tumor necrosis factor-alpha (TNF-α). The memory scores for healthy individuals in the population were obtained for each memory type and the population was genotyped via restriction fragment length polymorphism for the BDNF rs6265 (Val66Met) SNP and via pyrosequencing for the TNF-α rs113325588 SNP. Using univariate ANOVA, a significant association of the BDNF polymorphism with visual and spatial memory retention and a significant association of the TNF-α polymorphism was observed with spatial memory retention. In addition, a significant interactive effect between BDNF and TNF-α polymorphisms was observed in spatial memory retention. In practice visual memory involves spatial information and the two memory systems work together, however our data demonstrate that individuals with the Val/Val BDNF genotype have poorer visual memory but higher spatial memory retention, indicating a level of interaction between TNF-α and BDNF in spatial memory retention. This is the first study to use genetic analysis to determine the interaction between BDNF and TNF-α in relation to memory in normal adults and provides important information regarding the effect of genetic determinants and gene interactions on human memory.

Tuberculosis is associated with increased lung cancer mortality.

SETTING: Elderly persons living in the community in Hong Kong. OBJECTIVE: To examine the association between tuberculosis (TB) and lung cancer. DESIGN: Elderly clients enrolled in a health programme from 2000 to 2003 were retrospectively cross-matched with the territory-wide TB notification registry for TB before enrolment. The cohort was followed up prospectively through linkage with the territory-wide death registry for cause of death until 31 December 2011. All subjects with suspected malignancy or recent weight loss (≥5%) at enrolment and deaths within the first 2 years of follow-up were excluded. RESULTS: Of the 61,239 subjects included, 516 had TB before enrolment. After 490,258 person-years of follow-up, respectively 1344, 910 and 2003 deaths were caused by lung cancer, other tobacco-related malignancies and non-tobacco-related malignancies. TB before enrolment was associated with death due to lung cancer (Mantel-Haenszel weighted relative risk 2.61, 95%CI 1.82-3.74, P < 0.001) but not other malignancies after stratification by sex. TB remained an independent predictor of lung cancer death (adjusted hazard ratio 2.01, 95%CI 1.40-2.90; P < 0.001), after adjustment for multiple potential confounders. CONCLUSIONS: TB was independently associated with subsequent mortality due to lung cancer. This finding calls for intensification of tobacco control and better targeting of lung cancer screening in high TB burden areas.

Free-flap harvesting from paralytic limbs of poliomyelitis patients--a safe and feasible option.

BACKGROUND: Many patients who had childhood poliomyelitis are still suffering from the late sequalae of the condition. Free-flap harvesting from the paralytic limbs from these patients is a logical approach for functional preservation. However, concerns have been raised regarding its safety due to its hypoplastic vascular system and potential donor site healing problems. CASE REPORT: A 53-year-old man with known childhood poliomyelitis presented with left facial sarcoma. After wide excision, the defect was reconstructed with a dual-island fasciocutaneous-free anterolateral thigh flap harvested from his paralytic limb. The pedicle and perforators were found to be no different from those in normal limbs. His recovery was smooth without complications. CONCLUSIONS: On the basis of our experience and current evidence in the literature, we believe that free-flap harvesting from the paralytic lower limb in poliomyelitis patients is a safe option that incurs no additional risk and allows maximal function preservation.

The effect of Emdogain and platelet-derived growth factor on the osteoinductive potential of hydroxyapatite tricalcium phosphate.

The aim of this study was to determine whether hydroxyapatite ß-tricalcium phosphate (HA-TCP) either alone or coated with Emdogain (EMD) or recombinant human platelet-derived growth factor-BB (rhPDGF-BB) becomes osteoinductive in the murine thigh muscle model for osteoinduction. Twenty CD1 adult male mice had gelatin capsules implanted into the thigh muscle of both hind limbs. The capsules were either empty or contained one of the following: uncoated particulate HA-TCP, EMD-coated HA-TCP or rhPDGF-BB-coated HA-TCP. The implant sites were assessed histologically at 4 and 8 weeks. A semi-quantitative histological examination was performed to assess the inflammatory changes, reparative processes and osteoinduction within the graft site. At both 4 and 8 weeks, histological analysis failed to demonstrate any osteoinductive activity in any of the specimens from the experimental groups. A minimal chronic inflammatory response and foreign body reaction around the implanted materials was seen which reduced over time. The HA-TCP particles were embedded within fibrous connective tissue and were encapsulated by a dense cellular layer consisting of active fibroblasts and occasional macrophages with the thickness of this layer decreasing over time. The results of this study suggest that the use of commercially available HA-TCP alone or in combination with EMD or rhPDGF-BB is biocompatible but not osteoinductive in the murine thigh muscle model of osteoinduction. Coating HA-TCP with EMD or rhPDGF-BB does not enhance its osteoinductive potential.

Characterization of the atherosclerotic carotid bifurcation using MRI, finite element modeling, and histology.

Atherogenesis is known to be associated with the stresses that act on or within the arterial wall. Still, the uneven distribution of atherosclerotic lesions and the impact of vessel remodeling on disease progression are poorly understood. A methodology is proposed to study the correlations between fluid dynamic parameters and histological markers of atherosclerosis. Trends suggested by preliminary data from four patients with advanced carotid bifurcation arterial disease are examined and compared to hypotheses in the literature. Four patients were scanned using MRI and ultrasound, and subsequently underwent carotid endarterectomy. For each patient. a geometric model and a numerical mesh were constructed from MR data, and velocity boundary conditions established. Computations yield values for average wall shear stress (WSS), maximum wall shear stress temporal gradient (WSSTG), and Oscillatory Shear Index (OSI). Following surgery, the excised plaques were sectioned, stained for smooth muscle cells (SMC), macrophages (M phi), lipid (LIP), and collagen (COL), and analyzed quantitatively. Correlations attempted between the various fluid dynamic variables and the biological markers were interesting but inconclusive. Tendencies of WSSTG and WSS to correlate negatively with M phi and LIP, and positively with COL and SMC, as well as tendencies of OSI to correlate positively with Mphi and LIP and negatively with COL and SMC, were observed. These trends agree with hypotheses in the literature, which are based on ex vivo and in vitro experimental studies.

Transduction of dendritic cells with recombinant adenovirus encoding HCA661 activates autologous cytotoxic T lymphocytes to target hepatoma cells.

Transduction of recombinant adenovirus into dendritic cells (DCs) is a promising new tool for cancer vaccine development. Here, we report that an adenovirus vector carrying hepatocellular carcinoma (HCC) antigen HCA661 and infected into DCs generates T-cell immunity against hepatoma cells. HCA661 is a novel cancer/testis (CT) antigen screened by SEREX from sera of an HCC patient. We constructed a recombinant adenovirus expressing the full-length cDNA of HCA661 gene and then transduced immature DCs, which had been generated with GM-CSF and IL-4 from peripheral blood mononuclear cell of HLA-A2(+) healthy donors. The resulting adenovirus-transduced DCs differentiated in the presence of monocyte-conditioned medium and poly [I] : poly [C], expressing the surface markers of mature DCs, including CD83, CD80, CD86 and HLA-DR. After maturation, the transduced DCs transcribed HCA661 mRNA and were able to prime the naïve T cells to become cytotoxic T lymphocytes (CTLs). Intracellular flow cytometry and enzyme-linked immunospot assay showed that these CTLs were able to target a hepatoma cell line, HepG2, which is HLA-A2 and HCA661 positive. In summary, we found that this recombinant adenovirus can help to induce DC maturation and these mature DCs can activate T cells to target hepatoma cells. Therefore, this recombinant adenovirus may have potential for use in liver cancer immunotherapy.

Effects of 32P radioactive stents on in-stent restenosis in a double stent injury model of the porcine coronary arteries.

BACKGROUND: The major limitation of coronary stenting remains in-stent restenosis, due to the development of neointimal proliferation. Radioactive stents have demonstrated the ability to reduce this proliferation in the healthy nonatherosclerotic porcine animal model. However, inhibition of tissue proliferation in the in-stent restenotic lesion in a porcine model is not well characterized. The objective of this study was to examine the efficacy and safety of the 32P radioactive stent for the treatment of in-stent restenosis in a double stent injury model of the porcine coronaries. METHODS AND MATERIALS: Eighteen coronary arteries in 9 pigs underwent nonradioactive stent (8 mm in length) implantation. Thirty days after the initial stent implantation, a 32P radioactive stent (18 mm in length) with an activity of 0 and 18 microCi was implanted to cover the initial stent. The swine were killed 30 days after the second stent implantation. Histomorphometric analysis was performed for vessel area (VA), stent strut area (SSA), intimal area (IA), and lumen area (LA). RESULTS: Injury scores, VA, SSA, and LA were similar among the control and radiated groups. Neointimal formation was significantly reduced after placement of radioactive stents as compared to control in both the overlapped (0.93 +/- 0.12 vs. 1.31 +/- 0.51 mm(2), p < 0.05) and nonoverlapped segments (1.14 +/- 0.21 vs. 1.91 +/- 1.04 mm(2), p < 0.05). The smooth muscle cell index in the neointima was reduced. Intimal fibrin was increased in the radiated group as compared to the control (p < 0.01 respectively). CONCLUSIONS: 32P radioactive stents may be safe and effective in reducing neointimal formation leading to in-stent restenosis. Longer follow-up will be required to examine whether these positive findings can be maintained.

Decreased adventitial neovascularization after intracoronary irradiation in swine: a time course study.

BACKGROUND: Intracoronary radiation (IR) suppresses the formation of neointima after arterial injury in swine, through mechanisms incompletely understood. Neointimal development appears related to expansion of adventitial microvessels; we therefore examined the hypothesis that IR inhibits neointima formation through an anti-angiogenic effect. METHODS AND RESULTS: Juvenile swine were treated with either 0 or 15 Gy (192)Ir (gamma-source) and euthanized 3, 7, or 14 days later or treated with 18 Gy (90)Y (beta-source) and euthanized after 14 days. Adventitial area (AA), intimal area (IA), IA corrected for medial fracture length, and adventitial vessel area were assessed in both injured and uninjured segments by computer-aided histomorphometry on Verhoeff-Von Giesson stained sections. Adventitial vessel count (AVC) was enumerated visually on hematoxylin and eosin stained sections and confirmed by anti-factor VIII-associated antigen immunostaining for endothelial cells. AA and IA were reduced in injured arteries subjected to IR as compared to controls. The AVC was significantly lower in injured irradiated arterial segments as well as all uninjured segments as compared with injured control segments. In the injured and irradiated arteries, the AVC remained unchanged at 3, 7, and 14 days. The injured segments of arteries treated with IR demonstrated a significantly lower adventitial microvessel density (AVC/AA) as compared to the injured control segments. Comparison of gamma- and beta-irradiation at 14 days did not show any differences for vessel parameters and measurements of adventitial microvessels. IA and AVC were correlated positively (R(2) = 0.63, alpha = 0.79, p < 0.01). CONCLUSION: IR induced an early and sustained anti-angiogenic effect between 3 and 14 days. The relation between IA and AVC may indicate an antiproliferative effect associated with an anti-angiogenic effect independent of the type of radiation. CONDENSED ABSTRACT: Intracoronary radiation suppresses neointima formation after arterial injury in swine, through mechanisms and with consequences that are not fully known. Reduction of angiogenesis may inhibit restenosis. In the present study, intimal area and adventitial area were reduced in the intracoronary radiation groups 3-14 days after arterial injury as compared to their respective controls, with a parallel reduction in the adventitial vessel count and adventitial vessel density. Intimal area and adventitial vessel count were correlated positively. Neointima reduction after intracoronary radiation may depend not only on an antiproliferative effect but also on an anti-angiogenic effect.

A novel 32P deployable balloon system inhibits formation of neointima in porcine coronary arteries after balloon-overstretching injury.

BACKGROUND: Intracoronary radiation has shown the potential to reduce formation of neointima in porcine models of restenosis. OBJECTIVE: To investigate the feasibility, safety, and efficacy of a new 'deployable-balloon' device with radioisotope 32P integrated into the balloon material. METHODS: Ten swine were subjected to balloon-overstretching injury in 20 coronary arteries and were randomly allocated to receive a radiation dose of 0, 15, or 20Gy prescribed to 1 mm from the surface of the radioactive balloon material. The animals were killed 4 weeks after the procedure. Their coronaries were perfusion fixed and stained. Vessel parameters (area of intima and length of fracture) and area of thrombus area were analyzed by computer-aided histomorphometry. RESULTS: Radiation treatment with the new 32P balloon device was performed without complications. The lengts of fracture for the three groups were similar (NS). Formation of neointima after balloon injury was less in members of the radiated groups than it was in controls (area of intima/length of fracture was 0.70 +/-0.12 mm for controls, 0.08+/-0.13mm with 15 Gy, and 0.07+/-0.17 mm with 20 Gy; P < 0.001). Vessels treated with 20 Gy had a greater total area of thrombus (0.00+/-0.00 versus 0.51+/-0.98 mm2, P< 0.01). CONCLUSIONS: Intracoronary radiation therapy using a new 32P deployable-balloon system is feasible and safe. A radiation dose of 15 Gy was sufficient to inhibit neointimal response in the porcine coronary-balloon-injury model.

Intracoronary radiation with gamma wire inhibits recurrent in-stent restenosis.

To study the safety and efficacy of intracoronary gamma radiation delivered via a new high-activity (192)Ir source wire for the treatment of in-stent restenosis. In-stent restenosis results from neointimal tissue proliferation especially in its diffused form and presents a therapeutic challenge. Gamma radiation has been shown to decrease neointima formation within stents in animal models and in initial clinical trials. A total of 26 patients with in-stent restenosis underwent successful intervention and was treated with open-label (192)Ir using a high-activity line source. The specific activity of the source wire was 372+/-51 mCi, and the dwell time was 10.8+/-1.9 min. Primary endpoints were freedom from death, myocardial infraction (MI), and repeat target lesion revascularization (TLR) at 6 months. Secondary endpoints included angiographic restenosis and intravascular ultrasound (IVUS) neointimal hyperplasia. Procedural success was high (96.2%), and in-hospital and 30-day complications were low with no deaths, MI, or requirement for repeat revascularization. At 6 months, event-free survival was 85%: one patient required repeat PTCA, one underwent bypass surgery, and two had an MI. Baseline lesion length measured 15.77 mm. Follow-up angiography was available in 21/25 (84%) patients. The binary restenosis rates were 19.0% (4/21) in-stent and 23.8% (5/21) in-lesion. Follow-up IVUS was available in 20/25 patients. There was no increase in intimal hyperplasia from postintervention to follow-up (3.11.8 vs. 3.41.8 mm(2); P=.32). Eight patients had a reduction of neointimal intimal tissue at follow-up. These results indicate that intracoronary gamma radiation with the Angiorad source wire is safe and effective in preventing in-stent restenosis.

Differential remodeling after balloon overstretch injury and either beta- or gamma-intracoronary radiation of porcine coronary arteries.

BACKGROUND: Restenosis is a consequence of both neointimal hyperplasia and vessel remodeling. Prior studies have shown that intracoronary radiation (IR) prevents neointima accumulation, but its contribution to vessel remodeling is unknown. The purpose of this study was to evaluate the effect of IR on differential vascular remodeling after balloon angioplasty in porcine coronary arteries. METHODS: A total of 20 juvenile swine (30 coronary arteries) were subjected to overstretch balloon injury (BI) followed by IR with either beta- or gamma-radiation ((90)Y or (192)Ir). After 2 weeks following treatment, serial tissue sections were perfusion fixed and stained by hematoxylin and eosin (H&E), Verhoeff von Giesson (VVG), or Masson Trichrome. Adventitial area (AA), lumen area (LA), vessel area (VA), intimal area (IA), and IA corrected for medial fracture length (IA/FL) were quantified by digital image analysis. The vessel circumference was divided into two regions containing (1) the undisrupted region (UReg) with the undisrupted arc of media and internal elastic lamina (IEL) and (2) the disrupted region (DReg) with the disrupted arc between the medial tears. Quantitative regional analysis was performed by (1) measuring the IEL to define the UReg, (2) calculating the area of the UReg with the perimeter value derived from measurement of the IEL, and (3) calculating the DReg as follows: LA+IA-UReg. Immunohistochemical smooth muscle cell alpha-actin and Masson Trichrome were quantified by digital image analysis. RESULTS: The IA/FL was significantly smaller following treatment with (90)Y or (192)Ir vs. control (P<.01). A smaller AA was obtained following IR with both beta- and gamma-sources vs. control (P<.01). The UReg calculation was smaller in the irradiated arteries as compared to control (beta: 2.3+/-0.4 mm(2), gamma: 2.1+/-0.5 mm(2), P<.01 vs. control; control: 3.6+/-0.7 mm(2)). In contrast, the DReg was increased following IR, as demonstrated by the FL and the calculated area of the injured segment (control: 2.7+/-0.5 mm(2); beta: 5.5+/-1.1 mm(2), gamma: 5.5+/-1.1 mm(2), P<.01 vs. control). Adventitial alpha-actin positive cell density (CD) was decreased after IR; however, the collagen density was similar. In contrast, the neointimal collagen density in the injured segment was significantly decreased following IR. CONCLUSION: We consider that the global arterial remodeling after IR is a heterogeneous process that includes the absence of retraction in an UReg and a positive remodeling in the DReg as shown in the porcine coronary model. These changes in adventitia and neointima appear to contribute to differential vascular remodeling caused by IR in injured vessels.

Delayed re-endothelialization and T-cell infiltration following intracoronary radiation therapy in the porcine model.

PURPOSE: To evaluate the late induction of apoptosis following intracoronary radiation (IR) and the effects of IR on inflammatory cells. METHODS AND MATERIALS: Porcine coronaries were injured by balloon overstretch followed by either 0 or 15 Gy of 192Ir prescribed to 2 mm from the center of the source. Swine were euthanized at 3, 7, and 14 days posttreatment, and arteries were stained for markers of smooth muscle cells (SMCs alpha-actin), T cells (CD3), macrophages, endothelial cells, and apoptotic nuclei (terminal uridine nick end labeling, TUNEL). Intimal area (IA) and IA corrected for medial fracture length (IA/FL) were quantified by digital image analysis, which was also used to quantify the distribution of immunostain-positive cells in the adventitia, media, and neointima, respectively. RESULTS: IA/FL was significantly reduced following treatment with 15 Gy, in association with decreased SMC density. Following injury and IR, TUNEL- and CD3-positive cell density increased significantly, and density of macrophages was increased in the adventitia and neointima. Staining for endothelial cells revealed a delay of re-endothelialization after radiation treatment. CONCLUSION: Increased T-cell infiltration at the medial tear following IR, perhaps due to incomplete re-endothelialization, may indicate incomplete healing. The elevated apoptosis of these infiltrating T cells may indicate a mechanism for the resolution of inflammation.