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Purpose: To study the effect of various dose-volume parameters on the severity of vaginal stricture (VS) and the correlation of the latter with the posterior-inferior border of symphysis (PIBS) points in locally advanced cervical cancer patients treated with concurrent chemoradiation and brachytherapy., Methods and Materials: A prospective study was done on 45 histologically proven locally advanced cervical cancer patients between January 2020 and March 2021. All of them were treated with concurrent chemoradiation with 6 MV photon linear accelerator to a dose of 45 Gy/25 fractions in 5 weeks. Twenty-three patients were treated with intracavitary brachytherapy with a dose of 7 Gy/fraction/week for three fractions. Twenty-two patients were treated with interstitial brachytherapy, with 6 Gy/fraction for four fractions, each fraction 6 h apart. Grading of VS was done as per Common Terminology Criteria for Adverse Events version 5., Results: The median followup was 21.5 months. About 37.8% of patients had VS with a median duration of 8.0 months (4.0-12 months). About 22.2% had Grade 1, 6.7% had Grade 2, and 8.9% had Grade 3 toxicity. Doses at PIBS and PIBS-2 points had no correlation with vaginal toxicity, however, the dose at PIBS+2 was significantly associated with VS (p = 0.004). The treated length of the vagina at the time of brachytherapy (p = 0.001), initial tumor volume (p = 0.009), and vaginal involvement after completion of external beam radiotherapy (EBRT) (p = 0.01) were also statistically significant with the development of VS of Grade 2 or more., Conclusions: Dose at PIBS + 2, treated length of the vagina with brachytherapy, initial tumor volume, and post-EBRT vaginal involvement are strong predictors for the severity of VS., (Copyright © 2023 American Brachytherapy Society. Published by Elsevier Inc. All rights reserved.)

Background: An arteriovenous fistula (AVF) is the preferred vascular access for hemodialysis treatment. After creation many of the AVFs will never mature or if functioning will need an intervention within 1 year due to an AVF stenosis. Studies investigating possible therapies that improves the AVF maturation and survival are scarce. Far infrared therapy (FIR) has shown promising results. In minor single centre and industry supported trials FIR has shown improved AVF maturation and survival. There is a need of a randomized multicentre controlled trial to examine the effect of FIR on the AVF maturation and survival and to explore the possible AVF protective mechanism induced by the FIR treatment., Methods: This investigator initiated, randomized, controlled, open-labeled, multicenter clinical trial will examine the effect of FIR on AVF maturation in patients with a newly created AVF (incident) and AVF patency rate after 1 year of treatment in patients with an existing AVF (prevalent) compared to a control group. The intervention group will receive FIR to the skin above their AVF three times a week for 1 year. The control group will be observed without any treatment. The primary outcome for incident AVFs is the time from surgically creation of the AVF to successful cannulation. The primary outcome for the prevalent AVFs is the difference in number of AVFs without intervention and still functioning in the treatment and control group after 12 months. Furthermore, the acute changes in inflammatory and vasodilating factors during FIR will be explored. Arterial stiffness as a marker of long term AVF patency will also be examined., Discussion: FIR is a promising new treatment modality that may potentially lead to improved AVF maturation and survival. This randomized controlled open-labelled trial will investigate the effect of FIR and its possible mechanisms., Trial Registration: Clinicaltrialsgov NCT04011072 (7th of July 2019)., (© 2021. The Author(s).)

Purpose: Guidelines for the care of women undergoing pelvic radiation therapy (RT) recommend vaginal dilator therapy (VDT) to prevent radiation-induced vaginal stenosis (VS); however, no standard protocol exists. This review seeks to update our current state of knowledge concerning VS and VDT in radiation oncology., Methods and Materials: A comprehensive literature review (1972-2017) was conducted using search terms "vaginal stenosis," "radiation," and "vaginal dilator." Information was organized by key concepts including VS definition, time course, pathophysiology, risk factors, and interventions., Results: VS is a well-described consequence of pelvic RT, with early manifestations and late changes evolving over several years. Strong risk factors for VS include RT dose and volume of vagina irradiated. Resultant vaginal changes can interfere with sexual function and correlational studies support the use of preventive VDT. The complexity of factors that drive noncompliance with VDT is well recognized. There are no prospective data to guide optimal duration of VDT, and the consistency with which radiation oncologists monitor VS and manage its consequences is unknown., Conclusions: This review provides information concerning VS definition, pathophysiology, and risk factors and identifies domains of VDT practice that are understudied. Prospective efforts to monitor and measure outcomes of patients who are prescribed VDT are needed to guide practice., (Copyright © 2019 American Society for Radiation Oncology. All rights reserved.)

Objective: To explore the clinical value of endoscopic interventional therapy for locally recurrent primary lung adenoid cystic carcinoma (ACC). Methods: The clinical data of 42 patients with locally recurrent ACC were retrospectively analyzed, and the differences of tracheal and bronchial diameter, airway scoring grade and airway obstruction degree before and after treatment were compared among three treatment methods: bronchoscopic interventional therapy + palliative radiotherapy, interventional therapy alone, and non-interventional therapy. Log rank test and Cox proportional risk model multi-factor analysis were used to determine the prognostic factors of ACC patients with local recurrence, and the long-term effect of bronchoscopic interventional therapy on ACC with local recurrence was determined. Results: The median overall survival of 42 patients was 59 months and 5-year survival rate was 54.2%.Univariate analysis showed that vascularized cancer, pleural invasion, pulmonary atelectasis, incisal margin, microscopic classification, tumor diameter, initial TNM stage, ki-67 index, and treatment after local recurrence were associated with long-term survival of ACC patients with local recurrence (all P <0.05). Cox multivariate regression analysis showed that margin status ( RR =0.272, P =0.011), tumor diameter ( RR =2.586, P =0.005), initial TNM staging ( RR =0.369, P =0.035), ki-67 index ( RR =3.569, P <0.001), and treatment methods after local recurrence ( RR =0.126, P <0.001) were independent factors influencing the prognosis of ACC patients with local recurrence. After three months of treatment, the tracheal bronchus diameters, rating of shortness of breath, and degree of airway obstruction were all improved significantly (all P <0.05), both in the interventional therapy + palliative radiotherapy group [(14.5±2.8 mm, 0.86±0.45, (14.50±10.67)%, respectively], and the interventional therapy alone group [(13.7±2.3) mm, 0.97±0.25, (15.38±12.02)%, respectively]. Meanwhile, the difference before and after non-interventional therapy was not statistically significant (all P >0.05). 5-year overall survival rates were 55.8%, 46.6% and 42.6% for patients undergoing interventional therapy+ palliative radiotherapy, interventional therapy alone, and non-interventional therapy after recurrence, with statistically significant differences ( P =0.015). Patients underwent bronchial endoscopic interventional therapy and palliative radiotherapy had the best efficacy of treatment. Conclusion: Endoscopic interventional therapy plus palliative radiotherapy is an effective local palliative treatment for locally recurrent ACC patients, which can rapidly relieve airway stenosis, improve the quality of life of patients and prolong the survival time of patients.

Background: The purpose of this study is to investigate the clinical effectiveness of staging radioactive particle implantation guided by computed tomography (CT) and fiber-optic bronchoscopy in treating cancerous large airway stenosis., Methods: A total of 102 patients were included; 57 had undergone staging radioactive particle implantation guided by CT and fiber bronchoscopy and 45 did not. Patients were evaluated by CT and fiber-optic bronchoscopy to determine the feasibility of the implantation of radioactive seeds for the treatment of cancerous large airway stenosis. The treatment planning system (TPS) was used to plan the doses. Radioactive seeds were implanted using fiber-optic bronchoscopy. One week later, CT-guided implantation of radioactive seeds was performed., Results: The clinical evaluation showed complete, partial, slight, and non-response in 38, 14, 5, and 0 patients, respectively. None of the patients were found with serious complications. The diameter of the affected airway, Karnofsky score, dyspnea index, survival, and quality of life of the patients in both groups was significantly higher and significantly different after the treatment (P < 0.05). The dyspnea index was significantly lower in the treatment group as compared with the control group (P < 0.001)., Conclusion: CT- and fiber bronchoscopy-guided staging radioactive particle implantation has definite treatment effectiveness in treating cancerous large airway stenosis. It should be widely used in clinical practices.

For LDR-brachytherapy, a limited number of implant geometries and materials are available. To avoid wound healing related hyper-proliferation (stenosis, keloids) a novel radioactive foil system was developed based on beta emitting (32)P, which can be easily integrated in existing implants such as urethral catheters or bile duct stents. As substrate material for these foils PEEK (polyetherethercetone) was chosen because of its radiation hardness during neutron activation of (32)P. The activity was determined by liquid scintillation counting and gamma spectroscopy, dose distributions were measured with scintillation detectors and radiochromic films. The correlation between activity and dose was checked by Monte-Carlo-simulations (Geant4). Prototypes of the (32)P-implants have shown in wash-out tests the required tightness for sealed radioactive sources. In animal tests on urethra and bile duct, the uncomplicated and save application of (32)P-foils mounted on standard implants has been demonstrated, which is almost unchanged due to the simple radiation protection with plexiglass. This concept of radioactive implants with integrated (32)P-foils could extend essentially the application possibilities of LDR-brachytherapy., (Copyright © 2012. Published by Elsevier GmbH.)

Purpose: To determine optimal timing of assessing postradiation radiographic response on magnetic resonance imaging (MRI) scans in pediatric patients with diffuse intrinsic pontine glioma (DIPG)., Methods and Materials: Patients were treated on a prospective study at the National Cancer Institute (Protocol #06-C-0219) evaluating the effects of radiotherapy (RT). Standard RT was administered in standard fractionation over 6 weeks. Postradiation MRI scans were performed at 2 and 6-8 weeks., Results: Eleven patients with DIPG were evaluated. Median age was 6 years (range, 4-13 years). Patients were treated with external-beam RT to 55.8 Gy (n = 10) or 54 Gy (n = 1), with a gross tumor volume to planning target volume expansion of 1.8-2.0 cm. All patients received prescribed dose and underwent posttreatment MRI scans at 2 and 6-8 weeks. Pretreatment imaging revealed compression of fourth ventricle (n = 11); basilar artery encasement (n = 9); tumor extension outside the pons (n = 11); and tumor hemorrhage (n = 2). At the 2-week scan, basilar artery encasement improved in 7 of 9 patients, and extent of tumor was reduced in 5 of 11 patients. Fourth ventricle compression improved in 6 of 11 patients but worsened in 3 of 11 patients. Presumed necrosis was observed in 5 of 11 patients at 2 weeks and in 1 additional patient at 6-8 weeks. There was no significant difference in mean anteroposterior and transverse diameters of tumor between the 2- and 6-8-week time points. Six of 11 patients had increasing ventricular size, with no evidence of obstruction., Conclusions: There is no significant difference in tumor size of DIPG patients who have received standard RT when measured at 2 weeks vs. 6-8 weeks after RT. The majority of patients had the largest change in tumor size at the 2-week post-RT scan, with evolving changes documented on the 6-8-week scan. Six of 11 patients had progressive ventriculomegaly without obstruction, suggestive of communicating hydrocephalus. To the best of our knowledge, this is the first documentation of this phenomenon in this cohort of patients., (Published by Elsevier Inc.)

Purpose: The aim of this work is to compare the results of various treatment protocols used in palliative HDRBT with the view of analyzing differences in survival and diminishing breathing difficulties., Material and Methods: A total of 648 patients with advanced lung cancer were divided into two groups according to their clinical stage and the Zubrod-ECOG-WHO score. 303 (46.8%) patients received a total dose of 22.5 Gy in 3 fractions once a week, and 345 (53.2%) patients received a single fraction of 10 Gy. They were under clinical and endobronchial observation taking into consideration survival rates, local remission and duration of symptom relief such as dyspnoea, breathing, cough and haemoptysis., Results: There was no difference in the length of survival time between the two groups of patients (log-rank test, p=0.055). Patients showing improvement (objective response) survived longer than those who showed no change or progression (F Cox, p=0.000001). In multivariate analysis the other statistically important prognostic factors were: clinical stage of primary tumor (F Cox, p=0.000002), Zubrod-ECOG-WHO score (F Cox, p=0.002) and age of patients (F Cox, p=0.004)., Conclusions: The two treatment protocols showed similar efficiency in overcoming difficulties in breathing. Prognostic factors that significantly correlated with survival length were: grade of remission after treatment, clinical stage and performance status.

Purpose: Benign endobronchial granulation tissue causes airway obstruction in up to 20% of patients after lung transplantation or stent placement. High-dose-rate endobronchial brachytherapy (HDR-EB) has been successful in some cases refractory to standard bronchoscopic interventions., Methods and Materials: Between September 2004 and May 2005, 8 patients with refractory benign airway obstruction were treated with HDR-EB, using one to two fractions of Ir-192 prescribed to 7.1 Gy at a radius of 1 cm. Charts were retrospectively reviewed to evaluate subjective clinical response, forced expiratory volume in 1 second (FEV(1)), and frequency of therapeutic bronchoscopies over 6-month periods before and after HDR-EB., Results: The median follow-up was 14.6 months, and median survival was 10.5 months. The mean number of bronchoscopic interventions improved from 3.1 procedures in the 6-month pretreatment period to 1.8 after HDR-EB. Mean FEV(1) improved from 36% predicted to 46% predicted. Six patients had a good-to-excellent subjective early response, but only one maintained this response beyond 6 months, and this was the only patient treated with HDR-EB within 24 h from the most recent bronchoscopic intervention. Five patients have expired from causes related to their chronic pulmonary disease, including one from hemoptysis resulting from a bronchoarterial fistula., Conclusion: High-dose-rate-EB may be an effective treatment for select patients with refractory hyperplastic granulation tissue causing recurrent airway stenosis. Performing HDR-EB within 24-48 h after excision of obstructive granulation tissue could further improve outcomes. Careful patient selection is important to maximize therapeutic benefit and minimize toxicity. The optimal patient population, dose, and timing of HDR-EB should be investigated prospectively.

Objective: We wanted to evaluate the effectiveness of intraluminal irradiation with Holmium-166 ((166)Ho) for reducing the pseudointimal hyperplasia (PIH) in the transjugular intrahepatic portosystemic shunt (TIPS) tract in a swine model., Materials and Methods: TIPS was performed in 12 domestic pigs, after the creation of portal hypertension by intraportal injection of a mixture of N-butyl-2-cyanoacrylate (NBCA) and lipiodol. Five pigs first underwent intraluminal irradiation (30 Gy) in the parenchymal tract with using a (166)Ho solution-filled balloon catheter, and this was followed by the placement of a nitinol stent in the TIPS tract. For the seven control pigs, the balloon was filled with saline and contrast media mixture. Two weeks later, follow-up portography and histological analysis were performed., Results: TIPS was successfully performed in all twelve pigs with achieving artificially induced portal hypertension. Portography performed two weeks after TIPS showed the patent tracts in the TIPS tracts that were irradiated with (166)Ho (5/5, 100%), whereas either completely (5/6, 83.3%) or partially (1/6, 16.7%) occluded TIPS were seen in the seven pigs of the nonirradiated control group, except in one pig that experienced periprocedural death due to bleeding. Histological analysis showed a statistically significant difference for the maximal PIH (irradiated: 32.8%, nonirradiated: 76.0%, p < 0.001) between the two groups., Conclusion: Intraluminal irradiation with 30 Gy of (166)Ho for TIPS significantly improved the TIPS patency in a swine model of portal hypertension during a 2-week period of follow-up.

Linear polarized near-infrared light created with linear polarized near-infrared light therapy equipment (Super Lizer HA-550, Tokyo Iken Co, Ltd, Tokyo, Japan) has been used for the treatment of various painful disorders in Japan. Irradiation near the stellate ganglion with a Super Lizer (ISGL) is an especially notable therapeutic method used with stellate ganglion block (SGB) or substitutes for SGB. ISGL is a safe, simple, well-tolerated, and effective treatment. We examined the effects of irradiation with a Super Lizer applied to an area near the lumbar sympathetic ganglia on the ligated side in a chronic constriction injury (CCI) model, which is believed to be an animal model of complex regional pain syndrome (CRPS). Rats showing thermal hyperalgesia in a radiant heat test 1 wk postoperatively were used in Experiments 1 and 2: (1) Thermal hyperalgesia of irradiation group (n = 11) was less than that of the control or nonirradiation (n = 11) group at 1, 3, and 8 h after irradiation; however, the effect disappeared 12 h after irradiation. (2) Daily irradiation (n = 16) and 1 wk (n = 14) from 7 days after nerve ligation significantly shortened the interval from thermal hyperalgesia until recovery. Rats showing mechanical hyperalgesia in the von Frey hair test 1 wk postoperatively were used in Experiment 3: 1 wk irradiation beginning 7 days after nerve ligation (n = 9) did not promote the recovery from mechanical hyperalgesia. We speculate that repeated ISGL may be more effective than a single ISGL in alleviating pain in CRPS patients. We cannot explain the discrepancy between the results obtained in Experiments 2 and 3. We believe the results of this study are relevant to the effect of ISGL for patients with upper-limb CRPS: irradiation near the lumbar sympathetic ganglia of the rat is effective for thermal but not mechanical pain in CCI.

Purpose: To describe the outcome of intraluminal high-dose-rate (HDR) brachytherapy with metallic stenting in patients with obstructing extrahepatic cholangiocarcinoma., Materials and Methods: Eight patients with inoperable and/or unresectable extrahepatic bile duct carcinomas were treated with intraluminal brachytherapy (ILBT) followed by self-expandable metallic stent placement. Following percutaneous transhepatic drainage, ILBT was delivered by an HDR-Ir-192 source using the Micro-Selectron afterloading device. Two treatments were planned one week apart, with each treatment consisting of a single 10 Gy fraction. Biliary patency and palliative effect were assessed by serial labs (including bilirubin/alkaline phosphatase), symptomatic improvement, and/or cholangiography., Results: All eight patients tolerated the first application of ILBT well, and five of them completed two-intraluminal treatments. Six of eight had satisfactory control of jaundice until death. Pain relief was observed in four of five (80%) and pruritus in six of seven (86%) patients experiencing such symptoms. The mean and median times of stent patency were 6.9 and 5 months (range, 4-14), respectively. Gastrointestinal bleeding and/or cholangitis occurred in three patients., Conclusion: HDR ILBT with metallic stenting for patients with obstructive jaundice from extrahepatic bile duct carcinoma appears to be feasible and associated with acceptable toxicity. These treatments may lead to an improved quality of life in these patients.

Purpose: Early restenosis is one of the major complications after successful percutaneous transluminal angioplasty (PTA), in main, as well as peripheral, arteries. The effectiveness of hypofractionated external beam radiotherapy (EBRT) as a prophylaxis for restenosis was examined in a prospective, randomized, double-blind, clinical trial., Methods and Materials: Forty-eight patients underwent sham RT and 47 were treated with daily RT in 3-Gy fractions, to a total dose of 21 Gy. The follow-up lasted for 12 months, and the examinations included pressure measurements and calculations of the ankle-brachial index or duplex sonography ("peak velocity ratio"). If restenosis was suspected, additional angiography was performed., Results: No statistically significant difference was found between the treatment groups: sham RT 16 failures (33.3%) and EBRT group 21 failures (45.7%; p = 0.292). EBRT also showed no substantial effects on subgroups classified by the specific length of the lesion or in diabetic patients., Conclusion: External beam radiotherapy does not prevent restenosis. A reduction in the failure rate >8% using fractionated EBRT with doses aimed at keloid prevention can be ruled out with a probability of 97.5%. Endovascular brachytherapy remains the preferred therapeutic method for achieving restenosis prophylaxis through RT.

Objective: The aim of this study was to assess the impact of the diverticular disease (DD) on function and on postoperative complications of the colonic J-pouch (CJP) with pouch-anal anastomosis., Methods: Patients who underwent a CJP between December 1990 and August 2001, were retrospectively reviewed. The presence of DD in the CJP was assessed on pouchogram prior to ileostomy closure. A questionnaire designed to evaluate the degree of continence (total incontinence score (IS): 0 = worst, 20 = best) and pouch evacuation (total evacuation score (ES): 0 = worst, 28 = best) was used for comparison between patients with DD and those without DD (NDD)., Results: Sixty-six patients (47 males; 19 females) with a median age of 68 years (range 28-87 years) were included. The median follow-up period was 22 months (range 2-106 months). Twenty-four patients comprised the DD group and 42 were in the NDD group. The two groups were comparable for age, gender and time from ileostomy closure; all patients with postoperative chemoradiation therapy were in the NDD group. The total ES and IS total did not significantly differ between the two groups with a P-value of 0.11 and 0.09 respectively. Furthermore, there was no significant difference in the total incidence of pouch complications between the two groups (3 strictures, 1 leak, 1 fistula in the NDD group vs. 1 pelvic sepsis in the DD group; P = 0.4)., Conclusions: The presence of DD in a CJP does not seem to impact pouch function or the postoperative complication rate.

Objective: Migration of vascular smooth muscle cells (SMCs) into the subintimal space, and their proliferation and resultant deposition of extracellular matrix are key processes in the development of intimal hyperplasia, leading to vascular recurrent stenosis. The purpose of this study was to investigate the effects of clinically administered doses of gamma-radiation on SMCs and extracellular matrix proteins in vitro, to better understand how it impinges on cellular and extracellular components of recurrent stenosis., Methods: The effects of gamma-irradiation (10, 20 Gy) on SMC migration into three-dimensional collagen matrix gels was quantitated by calibrated light microscopy, and the release of metalloproteinases into conditioned media was investigated with an enzyme-linked immunosorbent assay and zymography. Collagen production was assayed with [(3)H]-proline incorporation, and SMC phenotype changes with confocal microscopy with a fluorescent alpha-actin antibody. The effect of gamma-irradiation on extracellular matrix was investigated by quantitating untreated SMC proliferation ((3)H-thymidine incorporation) on irradiated endothelial cell-derived matrix and by assessing structural collagen matrix changes with sodium dodecylsulfate polyacrylamide gel electrophoresis. All groups were compared with nonirradiated control groups., Results: SMC vertical migration was significantly decreased by gamma-irradiation (48% and 55%, respectively; P <.0001). Irradiation did not generate measurable matrix protein crosslinks, nor did it alter the production of metalloproteinases or collagen synthesis. However, gamma-irradiation decreased the ability of extracellular matrix to induce nonirradiated SMC proliferation (15% reduction; P =.0028). Moreover, gamma-irradiation reversed the secretory phenotype of cultured SMCs to a contractile type., Conclusions: The gamma-irradiation-induced reduction of cellular migration, changes in SMC phenotype, and functional activity of matrix-bound factors, and no measurable effects on the production of extracellular matrix proteins, may in part explain the diverse effects of gamma-irradiation on the restenotic response.

In recent years there has been intensive research on the use of ionizing radiation for inhibition of intimal hyperplasia (IH). Results have clearly established that beta ionizing radiation delivered from an endoluminal source after angioplasty inhibits intimal restenosis. This effect has been confirmed by recent multicenter clinical trials in patients undergoing coronary dilatation. The purpose of this study was to determine if gamma radiation therapy delivered superficially from an external source also reduced smooth muscle cell proliferation in two animals models-the first involving experimentally induced restenosis and the second involving anastomosis between a prosthesis and artery. Ultimately we hope to develop a therapeutic application for patients undergoing peripheral anastomoses, especially in the lower extremities. Two different animal models were used in this two-stage study. The first-stage rabbit model (model 1) involved balloon injury of the aorta to validate the dose effect of external beam irradiation. The second-stage porcine model (model 2) involved aortic bypass followed by external beam irradiation of the distal anastomosis site. In model 1 a total of 56 rabbits were studied. They were divided into five groups including one control group in which external radiation was not applied after balloon injury and four test groups in which external radiation was applied in a single fraction on day 0 at four different doses: 10 grays, 15 grays, 20 grays, and 25 grays. In model 2, a total of 24 pigs underwent aortic bypass with a 6-mm PTFE graft followed by irradiation of the distal end-to-side anastomosis at a dose of 20 grays on day 0. In both models specimens were harvested after 6 weeks and studied histologically after staining with HES and orcein, histomorphometrically by measuring intimal hyperplasia, and immunohistochemically using actin and factor VIII/von Willebrand factor (F VIII/vWF). The zones of study on the anastomosis were separated into base of the artery to the tip and heel of the anastomosis and the edge of the arteriotomy. Measurements were compared using the Mann Whitney test. In the first-stage model designed to study IH in rabbits, mean intimal and medial thickness values and the intima-to-media ratio showed no difference between the control group and the groups irradiated at doses of 10 grays and 15 grays (p = 0.111, p = 0.405, and p = 0.14); (p = 0.301, p = 0.206, and p = 0.199). Conversely, there was a significant difference between the control group and the groups irradiated at 20 grays and 25 grays (p < 0.0001, p = 0.107 and p = 0.008; p = 0.008, p = 0.155, and p = 0.008). Histological examination demonstrated extensive changes in the wall with high-grade fibrosis after application of ionizing radiation. In the second-stage swine model, irradiation significantly inhibited development of IH at the level of anastomosis both at the base of the artery (p < 0.01) (tip 0.06 vs. 0.27 mm and heel 0.04 vs. 0.36) and at the level of the arteriotomy at the suture site (p < 0.001) (0.13 vs. 0.86 mm). Immunochemical analysis of the thickened zones showed a positive reaction of endothelial cells to smooth muscle actin and F VII/vWF. Like irradiation applied using an endoluminal source, superficial gamma ionizing radiation from an external source inhibits IH. Analysis of the dose effect showed that the overall dose must be between 15 and 20 grays. External radiation also reduces overall IH at the anastomosis between a prosthesis and artery. Although these experimental data are promising, further study will probably be necessary before attempting to undertake clinical trials using external beam radiation therapy for patients undergoing peripheral anastomoses.

The study included 52 patients after gastrectomy for carcinoma of the proximal part of the stomach. Endoscopic laser therapy was made in 32 patients to reduce inflammation in the anastomosis zone 2-3 weeks after surgery. Drug therapy was made in 20 patients within the same time period. Histochemical study of the biopsy material of esophageal and intestinal part of the anastomosis was carried out. It is revealed that application of copper vapor laser early after surgery reduces edema and inflammation in the anastomosis zone for 2 weeks as well as accelerates the growth of granulation tissue forming a delicate scar thus preventing formation of scar stenosis.

Purpose: Trains of multiple 192Ir seeds are used in many clinical trials for intravascular brachytherapy. 192Ir source is commonly considered as a gamma emitter, despite the understanding that this radionuclide also emits a wide range of electron and beta energies, with a similar range of energy. The high dose from betas and electrons in the submillimeter range due to unsealed ends of seed sources should be precisely quantified to fully understand the backdrop for complications associated with 192Ir coronary artery brachytherapy., Methods and Materials: Monte Carlo simulations (MCNP4C code) were performed for a model 5-seed 192Ir train used in SCRIPPS, GAMMA, and the Washington Radiation for In-Stent Restenosis (WRIST) randomized clinical trials. A stack of radiochromic films was also used to measure the dose distributions for an actual 6-seed train., Results: In the submillimeter range very close to the source, Monte Carlo results show that betas and electrons deposit a higher dose than 192Ir photons (gamma and X-rays) over the interseed gap. A high luminal dose from the combined effects of betas, electrons, and photons emitted from 192Ir can be deposited, particularly between seeds. When prescribing 15 Gy at 2 mm, the combined dose can be as high as 160 Gy at 0.5 mm. Different peak doses near the interseed gaps were noted, which may be due to variability of seed-end surfaces and nonuniformity of seed activity within a real multiseed train. Dose-volume histograms (DVH) of lumen surfaces were evaluated for an eccentric seed train. The DVH parameters indicating the extent of hot spots in the lumen wall, DV(10), DV(5), DV(2), and DV(1) (dose received by 10, 5, 2, 1% respectively of the total lumen surface), can be as high as 55, 76, 81, and 155 Gy for a lumen with 3-mm diameter, and 75, 80, 110, and 158 Gy for a narrow 2-mm lumen., Conclusion: 192Ir multiple seed trains used in the SCRIPPS, GAMMA, and WRIST trials can deposit a very high dose to the luminal wall. A particularly high electron and beta dose can be delivered near the interseed gap if the source is not centered in the catheter and lumen. The dose from 192Ir betas and electrons may partially explain adverse outcomes reported from 192Ir multiseed clinical trials. Improvement of the encapsulation design to filter out the betas and electrons should be seriously considered.

Purpose: To investigate the effect of aortic bifurcation and iliac geometry on centered endovascular irradiation (CEI) of femoropopliteal arteries and evaluate procedure-related complications., Materials and Methods: In an experimental tubing model, crossover delivery of the dummy wire by an afterloader using different sheaths (Type I: noncrossover; Type II: crossover, length 40 cm; Type III: crossover, length 65 cm) was examined at simulated angles between 20 degrees -100 degrees (aortic bifurcation) and 0 degrees -100 degrees (iliac vessels). In the clinical phase, 28 heparin-anticoagulated patients underwent percutaneous transluminal angioplasty (PTA) for femoropopliteal stenoses followed by CEI (192-iridium, 14 Gray at 2 mm depth of the vessel wall) delivered with the centering catheter (crossover from contralateral leg using a 65-cm-long 8F sheath in 13 patients, noncrossover from ipsilateral leg using a 10-cm 8F sheath in 15 patients). Measurement of the aortic bifurcation angle before advancement of the crossover sheath and rating of iliac artery tortuosity on both sides was retrospectively performed on angiograms. Fifteen controls received no post-PTA CEI., Results: Experimental delivery of the dummy wire was not possible at aortic angles less than 40 degrees with Type I, 60 degrees with Type II, and 30 degrees with Type III sheaths. Advancement of the centering catheter was possible in all patients. CEI failed in two patients with crossover (aortic angle <40 degrees ) and in one obese patient with antegrade approach because advancement of the dummy wire was impossible. Thromboembolism rate was 4.6% during irradiation (2.3% after PTA alone)., Conclusions: CEI in femoropopliteal arteries has a risk of procedure-related thromboembolic complications. Efficacy is affected by vessel geometry.

Purpose: To evaluate the technical feasibility and efficacy of endovascular brachytherapy for prophylaxis of restenosis after femoropopliteal percutaneous transluminal angioplasty (PTA)., Materials and Methods: Ten patients with recurrence of stenosis in the femoropopliteal region underwent PTA followed by endovascular irradiation with Iridium-192 a high-dose rate after-loading technique. We used a single fraction of dose 12 Gy given in 3 mm from the source axis in the stenotic vessel segment., Results: During follow-up of 59-580 days restenosis occurred in four patients 111, 460, 472 and 580 days after irradiation. All other patients are without restenosis. No radiation-associated side effects were observed., Conclusions: Endovascular brachytherapy of restenosis in the femoropopliteal region is technically feasible, and may be done as a part of the PTA. These encouraging results open the possibility of reduction of restenosis by the present method.

Purpose: The stenosis or occlusion of transjugular intrahepatic portosystemic shunt (TIPS) occurs in up to 75% of patients within 12 months after treatment. The aim of our investigation was to evaluate the feasibility, safety and efficacy of intraluminal high-dose rate brachytherapy (HDRBT) with Iridium-192 following TIPS revision to prevent restenosis due to pseudointimal hyperplasia., Materials and Methods: Between September and November 1996, intraluminal BT was performed in five patients after TIPS revision. The indications for initial TIPS were a Budd-Chiari syndrome in two female patients and recurrent variceal bleeding by alcoholic liver cirrhosis in three male patients. TIPS was created with Wallstents (10 mm diameter in four patients) and Palmaz stent (10 mm diameter in one patient). The re-dilatation was done in all five patients 6 months after first stenting because of restenosis (>50% stent lumen reduction) or occlusion of the stent. A 5-French closed-tip, noncentered BT delivery catheter was used for subsequent radiotherapy. The whole length of the stent and performed dilatation (interventional length - IL) was taken as clinical target length (CTL). A 10-mm safety margin was added proximal and distal to the CTL due to uncertainties of BT source positioning, so forming the planning target length (PTL). To ensure that prescribed dose covers the whole PTL, the active source length (ASL) was 5 mm longer proximal and distal than PTL, so forming the reference isodose length (RIL). A dose of 12 Gy was prescribed in 3 mm distance from the source axis in the mid-plane of the applicator for three patients and in 5 mm distance for two patients., Results: A normal patency (<50% lumen reduction) of the stent was achieved at 44 months follow-up (duplex sonography+portography) in all three patients with liver cirrhosis, whereas further revisions were necessary in two patients with Budd-Chiari syndrome (after 5.5 and 18 months). No acute, subacute or late brachytherapy (BT)-related side effects were seen until now., Conclusions: HDRBT following TIPS revision was safe and feasible in all patients. The exact impact of BT on the TIPS patency should be evaluated in larger clinical trials. Moderate dose escalation and use of today's commercially available centering radiation catheters seem to be necessary.

Purpose: The aim of the Vienna-2-trial was to compare the restenosis rate of femoropopliteal arteries after percutaneous transluminal angioplasty (PTA) with or without intraarterial high-dose-rate (HDR) brachytherapy (BT) using an (192)Ir source., Materials and Methods: A prospective, randomized trial was conducted from 11/96 to 8/98. A total of 113 patients (63 men, 50 women), with a mean age of 71 years (range, 43-89 years) were included. Inclusion criteria were (1) claudication or critical limb ischemia, (2) de-novo stenosis of 5 cm or more, (3) restenosis after former PTA of any length, and (4) no stent implantation. Patients were randomized after successful PTA for BT vs. no further treatment. A well-balanced patient distribution was achieved for the criteria used for stratification, as there were "de-novo stenosis vs. restenosis after former PTA," "stenosis vs. occlusion," "claudication vs. critical limb ischemia" and above these for "diabetes vs. nondiabetes." PTA length was not well balanced between the treatment arms: a PTA length of 4-10 cm was seen in 19 patients in the PTA alone group and in 11 patients in the PTA+BT group, whereas a PTA length of greater than 10 cm was seen in 35 patients and 42 patients, respectively. A dose of 12 Gy was prescribed in 3-mm distance from the source axis. According to AAPM recommendations, the dose was 6.8 Gy in 5-mm distance (vessel radius + 2 mm). Primary endpoint of the study was femoropopliteal patency after 6 months., Results: PTA and additional BT were feasible and well tolerated by all 57 pts in this treatment arm. No acute, subacute, and late adverse side effects related to BT were seen after a mean follow up of 12 months (6-24 months) in 107 patients (PTA n = 54; PTA+ BT n = 53). Crude restenosis rate at 6 months was in the PTA arm 54% vs. 28% in the PTA + BT arm (chi(2) test; p < 0.013). Actuarial estimate of the patency rate was at 6 months 45% vs. 72% (p < 0.004). Comparison of restenosis rates for the different subgroups with risk factors (restenosis after former PTA, occlusion and PTA length >10 cm) showed significant decrease of the restenosis rate, if BT was added. Significant reduction was not achieved in diabetes patients., Conclusion: BT after femoropopliteal PTA is feasible and a safe therapeutic option. No BT related morbidity was observed. A significant reduction of the restenosis rate was obtained in the PTA+BT arm. Subgroup analysis showed significant decrease of restenosis rate in the subgroups with restenosis after former PTA, occlusion and PTA length of greater than 10 cm. With dose escalation and reduction of dose variation by a centering device a further significant decrease of restenosis rate can be expected.

One of the most intriguing developments in recent years towards prevention of restenosis after angioplasty is the use of ionizing radiation. The background for the use of radiation treatment for this application is sound, since radiation is used not only to treat malignant cancerous growths but also is used for treatment of benign hyperplastic disorders such as post-surgical keloid formation and recurrence of pterygium after surgical removal. Restenosis can be considered a form of overexuberant wound healing triggered by angioplasty. Ionizing radiation inhibits serum-stimulated proliferation of many cell types including fibroblasts and smooth muscle cells in vitro and also suppresses the synthesis of collagen by cultured fibroblasts. Liermann who showed inhibition of post-stent restenosis first used ionizing radiation for restenosis prevention clinically in iliac and iliofemoral arteries. Subsequently, extensive animal studies in various restenosis models have shown a profound inhibitory effect of catheter-based radiation (endovascular brachytherapy) on neointima formation and overall vessel shrinkage (negative remodeling). Based on these results clinical trials have been initiated with several types of devices and isotopes. Among these are 192Ir, 32P, 90Y, 90Sr/Y and 188Re. Additionally, radioactive stents have been developed; devices for clinical use are made radioactive at the microCi level by surface implantation of 32P ions. Results from early clinical trials are encouraging and brachytherapy appears safe for clinical use and at an appropriate dose, may be highly effective for restenosis prevention.

Purpose: Ionizing radiation has been shown to be a powerful inhibitor of neointimal hyperplasia following arterial injury in several animal models of post-percutaneous transluminal coronary angioplasty (post-PTCA) restenosis. This was previously shown to be associated with a reduction in smooth muscle cell (SMC) mitotic activity. This study evaluated the effect of intraarterial beta irradiation on the arterial wall SMC density and apoptosis., Methods and Materials: Twenty-five carotid and 7 iliac arteries of hypercholesterolemic New Zealand white rabbits were injured using the Baumgartner technique. The impact of an 18 Gy beta radiation dose administered after balloon injury was studied and compared to a nonirradiated injured control group. The medial SMC density as well as the percentage of apoptotic cells were determined at 8 days, 21 days, and 6 weeks after injury using an automated computer-based software. Apoptotic cells were identified using in situ end-labeling of fragmented DNA., Results: The values for medial apoptosis in control vs. irradiated arteries were: 0.014 +/- 0.023 vs. 0.23 +/- 0.28%, p = NS, at 8 days; 0.012 +/- 0.018 vs. 0.07 +/- 0.07%, p = 0.05, at 21 days; and 0 +/- 0 vs. 0.16 +/- 0.11%, p = 0.03, at 6 weeks. The overall incidence of medial apoptotic cells at all time points was 0.01 +/- 0.017 vs. 0.13 +/- 0.14% in controls and irradiated arteries respectively, p = 0.004. Medial SMC density was significantly decreased in irradiated arteries in comparison with controls (p < 0.01 at all time-points)., Conclusions: Intraarterial beta irradiation stimulates medial SMC apoptosis in balloon-injured arteries. This, together with a decrease in SMC mitotic activity, contributes to a decrease in the arterial wall cellularity.

Purpose: In catheter-based intravascular brachytherapy, either photon or beta emitters are often used in a linear arrangement so that blood vessels of 10-30 mm lengths can be treated. With a line source, the dose gradient in the radial direction and longitudinal direction depend on the type of radionuclides used in the treatment. The purpose of this study was to investigate the dose fall-off at the edges of a linear source in a blood vessel for different types of photon and beta emitters., Materials/methods: Dose distributions were calculated on cylindrical blood vessels of various radii. Radioactive sources of 192Ir, 125I, 103Pd, 188Re, 32P, and 90Y/Sr were studied. All the sources were assumed to be in the form of a line. The dose rate at a point in space produced by a radioactive source was computed by integrating the point dose rate kernel of the corresponding radionuclide over the radioactive line. The point dose rate kernel was computed with Monte Carlo simulation of radiation transport. The edge effects were characterized with three newly defined quantities: longitudinal dose uniformity (LDU), effective coverage length (ECL), and margin length (ML). LDU was defined as the ratio of dose at a distance along the long axis of the vessel to the dose at center. ECL was defined as the length over which the LDU was greater than 0.95. ML was defined as half of the length difference between source length L and ECL, which is essentially the length segment at each edge that is covered by the source physical length but is being underdosed., Results: All beta emitters provided more uniform dose distributions and covered a larger portion of blood vessels longitudinally than photon emitters. Typical MLs were 2-3 mm for beta emitters and 4-6 mm for gamma emitters. As the radial depth of the point of interest increased, both the LDU and ECL decreased and ML increased. The ML increased from 2 to 3 mm for beta emitters and from 4 to 6 mm for photon emitters when the radial depth of the point of interest increased from 1.5 to 2.5 mm (typical proximal and distal media points for a 3-mm diameter lumen). The ML increased with increasing source length for all radionuclides. For beta emitters the ML increased initially from 1.5 mm to more than 2.5 mm as source length increased from 5 to 10 mm. When the source length was longer than 15 mm, the ML remains nearly constant, about 3 mm. For photon emitters, ML increased continuously from 1.5 mm to more than 6.0 mm, as source length increased from 5 to 50 mm., Conclusions: A formalism to quantify the dose uniformity along the length of a blood vessel undergoing catheter-based intravascular brachytherapy has been developed. This formalism was used to study the edge effects at the ends of several beta and photon sources. The results indicated that for a centered source the ML at each end due to penumbra effects was about 2 to 3 mm for beta emitters; about 4-6 mm for photon emitters. The ML increases as the radial depth of point of interest in the vessel increases. The ML increases also with increasing source length, especially for photon sources.

Purpose: Using a radioactive solution-filled catheter for intravascular irradiation has the potential problem of chemical and radiological toxicity in the case of a balloon rupture. In order to reduce this risk, an innovative concentric balloon catheter was developed., Methods and Materials: The concentric balloon was made by inner and outer balloons filled with saline and radioactive solution, respectively. The optimal inner radius was determined by comparing the dose rate reduction vs. the volume reduction for various inner and outer radii for 188Re, 32P, and 90Y solutions., Results: For a balloon with an outer radius of 1.5 mm, there was no advantage of a concentric balloon. For balloons with outer radii of 3.0 and 5 mm, the optimal inner radius was 1.5 and 3 mm, respectively., Conclusions: With the newly designed concentric balloon, the risk of toxicity can be reduced while keeping the dose rate high enough so that the treatment times within tolerable limits are still maintained.

Purpose: To evaluate the technical feasibility and efficacy of endovascular brachytherapy with Iridium-192 in the prevention of restenosis caused by neointimal hyperplasia of transjugular intrahepatic portosystemic shunt (TIPS)., Materials and Methods: The endovascular brachytherapy with high dose rate automatic afterloading system was performed in six patients with recurrent of stenosis of TIPS. We used a single dose fraction of 12 Gy delivered at 3 millimeter (mm) from the source axis to the stenotic vessel segment in five patients with spiral Z-stent, and 15 Gy at 5 mm in one patient with Wallstent., Results: Follow-up time ranged from 148 to 639 days. In one patient, restenosis occurred in the treated vessel segment, diagnosed 71 days after endovascular brachytherapy by doppler ultrasound. All other patients were, during the follow-up time, without restenosis in the irradiated vessel segment. Radiation-associated side effects were not observed., Conclusions: Endovascular brachytherapy of TIPS is technically feasible and may be done as a part of the percutaneous revision of the shunt. This pilot study may be the largest experience of treating TIPS restenosis in humans to date. For definitive conclusions, a lot of studies are needed.

Purpose: To evaluate the ability of 32phosphorus intraluminal irradiation to reduce pseudointimal hyperplasia in a transjugular intrahepatic portosystemic shunt (TIPS)., Materials and Methods: TIPS were successfully placed in 11 swine with normal portal pressures. Six animals received 15.2 Gy intraluminal irradiation to the hepatic parenchyma and venous outflow tract at the time of TIPS placement with use of a NA32P-filled balloon angioplasty catheter. Five control animals underwent TIPS and balloon angioplasty with saline. All animals were followed up for 28 days, at which time percutaneous portography was performed, the animals were killed, and the tissue around the TIPS stent was processed for histologic analysis. Maximum pseudointimal hyperplasia as a percentage of estimated TIPS diameter was calculated for each animal., Results: At the time of euthanasia, all five control TIPS and all but one irradiated TIPS were occluded. Histologic analysis demonstrated considerable variability in the degree of pseudointimal hyperplasia within each TIPS and between animals. No statistically significant difference was found in the maximum pseudointimal hyperplasia, measured as a percentage of stent radius, between control (80.2%+/-17.4%) and irradiated animals (69.2%+/-25.2%)., Conclusions: Irradiation of TIPS with 15.2 Gy 32P delivered at the time of TIPS placement did not significantly improve TIPS patency or reduce the degree of pseudointimal hyperplasia in swine with normal portal pressures.

The most common cause of morbidity and mortality in the United States is vascular disease, which afflicts a wide spectrum of organs such as the heart (cardiovascular system), brain (cerebrovascular system), kidney (renal system), liver (hepatic system), and extremities (peripheral vascular system). The most common pathology of vascular diseases is occlusion. Percutaneous Transluminal Angioplasty (PTA) is currently the most common nonsurgical treatment for obstructive arteries. Unfortunately, the long-term effectiveness of PTA is limited by a high restenosis rate. Efforts to reduce post-PTA restenosis, including laser, mechanical atherectomy, intravascular stenting, and pharmacologic agents, have not been successful. With recent advances in the pathogenesis of restenosis, we have learned that the major problem is the intimal hyperplastic reaction in response to vessel injury. Encouraging animal data in the use of various radiotherapeutic approaches to prevent restenosis has led to a large number of multi-national, multicenter, randomized trials on coronary vascular systems. Because early results have been in favor of radiation therapy, and because the basic process of restenosis is similar for coronary and noncoronary vascular systems, many investigators extend the application of radiotherapy to the prevention of restenosis in peripheral vascular systems. However, the clinical scenarios are much different for peripheral vascular systems than for the coronary vascular system. This article discusses the current views of the pathophysiology of restenosis, major clinical trials, and perspectives on future studies. Experimental studies on animal models have documented the profound effects of endovascular brachytherapy in reducing restenosis caused by angioplasty and stenting. Early results of clinical trials are encouraging and confirm these positive results. Long-term follow-up data are needed to show that radiation does prevent, not merely delay, restenosis; Several areas of opportunity exist for both basic science research and clinical studies to enhance our knowledge of the pathophysiology. This would optimize the treatment strategy, maximizing the benefits and minimizing late complications.

Since its discovery, radiation has been used to treat numerous ailments, including many benign conditions. The most susceptible disorders have included keloids, heterotopic bone formation, and, most recently, vascular restenosis. These disorders are proliferative in nature and fall under the category of excessive wound healing or scar formation after trauma. In addition, radiation has been used for its immunosuppressive quality, eg, in organ transplantation to suppress graft rejection and in the treatment of autoimmune diseases. In this article, we have chosen keloids as an archetype for radiation use with benign conditions; the radiation inhibition of vascular restenosis will be used as a prototype to explore a paradigm for the molecular and cellular basis of radiation treatment for selected benign disorders. Vascular restenosis is currently one of the new frontiers of radiation therapy and offers opportunities to explore the role of inflammatory or immune cell responses in benign conditions that lead to excessive fibrogenesis and require treatment. The pathophysiology of surgical wound healing has not been avidly studied in the radiobiologic laboratory setting. However, the paradigm we propose for the effectiveness of radiation treatment for benign conditions is based on the model offered by Clark. He describes three phases of molecular and cellular events in which an inflammatory phase precedes the fibrogenic phase, occurs within hours of injury, and continues for weeks. We postulate that the radiosensitive targets within the vascular milieu are the monocyte/macrophages that would otherwise act as the trigger for the induced cytokine cascade, leading to the myofibroblast being recruited from a quiescent to a proliferative phase, resulting in fibrogenesis.

Intraluminal irradiation of coronary and peripheral arteries has been shown to reduce neointimal hyperplasia following balloon angioplasty, thereby inhibiting restenosis. Several irradiation techniques are being investigated, including temporary intravascular insertion of high activity gamma- or beta-emitting seeds and wires; inflation of dilatation balloon catheter with radioactive liquid or gas; insertion of miniature x-ray tubes via coronary catheters; permanent implantation of radioactive stents; and postangioplasty fractionated external beam irradiation. Unlike conventional brachytherapy, intravascular treatment of restenosis requires accurate knowledge of dose at distances of 0.5-5 mm from the radioactive source. This requirement presents special problems with regard to source calibration and dose specification, because dose gradients at such close distances from a radioactive source are extremely large. This makes it virtually impossible to define the characteristics of an ideal radiation source without some knowledge of the location and radiosensitivity of the target tissues, plus the radiotolerance of normal tissues. Hence, the current debate over whether beta or gamma sources are to be preferred. Imprecise knowledge of dose-volume effects for coronary arteries, plus uncertainties in the biological time sequencing of restenosis fuel a second debate on whether external beam treatments may be efficacious, and whether or not permanent radioactive stents may prove superior to high dose, single fraction brachytherapy. We review here the dosimetric properties of the various irradiation techniques and isotopes that have been proposed, including aspects of radiation safety, dose homogeneity, and practical aspects of source delivery.

Form March, 1991, to September, 1995, twenty-nine patients with endobronchial neoplastic stenosis were treated with high dose rate (HDR) brachytherapy at the Casa Sollievo della Sofferenza Hospital in San Giovanni Rotondo (Foggia, Italy). Fifteen patients had hemoptysis, 10 dyspnea, 6 constant cough and 6 lung atelectasis. The total dose, specified at 1 cm from the source, ranged 5 to 21 Gy and the fraction doses 5 to 15 Gy. Fourteen of 29 patients (48%) died. The mean survival is 7 months, with the follow-up ranging 1 to 22 months. Subjective responses were achieved in 78.4% of cases, with 67.6% complete and 10.8% partial remission rates. Complete remission of hemoptysis was observed in 100% of patients. Dyspnea improved in 70%, cough in 46.4% and atelectasis in 83.2%. Endoscopic findings, 1 month after the end of brachytherapy, showed a response in 79.4% of patients. The complication rate was 13.8% (1 tracheoesophageal fistula, 2 pulmonary hemorrhages and 1 cavitary necrosis). Even though the number of treated patients is small, our experience confirms the efficacy of HDR endobronchial brachytherapy in the palliation of lung cancer-related symptoms. Literature data show that brachytherapy improves the quality of life in the patients with poor prognosis who are otherwise untreatable. The HDR technique is more accurate than the LDR technique and therapy is better tolerated also because execution time is shorter. Prospective clinical trials are needed to investigate the most effective total doses and fractionations and to better define the role of brachytherapy in the curative treatment of lung cancer.

Purpose: During the evolution of lung cancer, bronchial obstruction is often noticed and is sometimes responsible for serious symptoms. Several methods of desobstruction can be proposed, including brachytherapy., Materials and Methods: One hundred forty-nine patients presenting with endobronchial brachytherapy were included into the study. Seventy-three were treated with curative intent, 47 with palliative intent and 29 with a combination of external irradiation and brachytherapy. We usually delivered a series of two 7-Gy fractions (1 cm from the catheter), the treatment being repeated one, two or three times., Results: When all symptoms were taken into account, respiratory function improvement was present in 79% of the patients. Among the 132 tumors that could be evaluated via a new endoscopy 2 months after treatment, 64 (48.5%) were in complete histological remission. The median survival was 14.4 months for the patients treated with curative intent. Eleven massive hemoptysies and 13 radiation bronchitis were observed., Conclusion: These results confirm the feasibility and good results related to endobronchial brachytherapy, though controlled studies are needed to better define its place in the therapeutic strategy of bronchial carcinomas.

Background: Intra-arterial gamma irradiation has been shown to reduce restenosis after balloon angioplasty. The use of beta emitters should allow similar effects while inducing less undue tissue irradiation radioprotection problems., Methods and Results: Flexible 90-yttrium (90Y) coils inside a centering balloon were used to allow homogeneous intraarterial dose delivery. One carotid and one iliac artery of 21 hypercholesterolemic rabbits were deendothelialized and then irradiated. Four dose schedules were studied: (1) control (dilated, nonirradiated); (2) 6 Gy; (3) 12 Gy; and (4) 18 Gy. Arterial specimens were histologically evaluated at 8 days and at 6 weeks. For all radiation doses at 8 days compared with controls, there was a significant decrease in bromodeoxyuridine-labeled cells (245 +/- 93 cells/cm in control, 42 +/- 27 in 6 Gy, 72 +/- 107 in 12 Gy, and 2 +/- 2 in 18 Gy groups; P < .001) and in total neointimal cells (891 +/- 415 cells/cm in control, 79 +/- 43 in 6 Gy, 192 +/- 264 in 12 Gy and 22 +/- 13 in 18 Gy groups; P < .0002). At 6 weeks, computer-derived histological percent area stenosis was reduced from 26 +/- 10% in the control group to 1 +/- 1.3% in the 18 Gy group (P < .0001), but lower doses had no significant effect., Conclusions: Administration of intra-arterial beta irradiation with a 90Y source is technically feasible and compatible with an ordinary catheterization laboratory environment. A dose of 18 Gy effectively induces long-term inhibition of neointimal hyperplasia.

Palliative oncological therapy attempts to maintain survival with a good quality of life in patients who cannot be cured. The aim of the treatment is in most cases the relief of agonizing or restricting symptoms. With metastases in particular, the shortest possible treatment period is desirable. The decision as to the best radiation treatment modality or technique depends on the individual needs and risks in each patient. Evaluation of the treatment results is difficult. It is worthwhile to use very specialized radiation techniques to improve the quality of life, but they should not replace supportive care and attention to the patients' psychological problems.

A case of undifferenciated carcinoma of the left lung with stenosis of the right pulmonary artery is reported. The characteristic clinical features of the systolic ejection murmur in pulmonary artery stenosis are recalled as well as the data from phonocardiographic, angiographic, and hemodynamic investigations. After radiation therapy, the grade of the systolic murmur decreased frankly although transiently. Noticeable decrease of the stenosis was substantiated by a second angiography. This improvement was still apparent 16 months later during chemotherapy.

The obstruction of the superior vena cava by tumor is recognized as an acute or subacute oncologic emergency. Rapid high-dose irradiation to the mediastinum is shown to be effective therapy for a superior vena caval obstruction. In our series 35 patients have been treated with rapid high-dose irradiation between January 1971 and July 1977. The present treatment consists of 400 rad given in a daily midplane dose for 3 days, and then slowing to 150 rad midplane per day to a total dose of 3000 rad over 15 fractions. There have been no instances of exacerbations of symptoms or severe complications from this treatment. There have been 2 failures of the 35 patients treated with this regimen. Both were shown at autopsy to have massive thrombi obstructing the superior vena cava. Six years of experience using this regimen has proven to be a safe and effective means of treatment for superior vena caval obstruction.

Fifty-six cases of bronchogenic carcinoma with mediastinal compression were analyzed retrospectively. Microscopic confirmation was obtained in 23 patients and small cell carcinoma was most frequent. Radiation treatment gave complete remission in about 70 per cent when the total tumour dose exceeded 35 Gy fractionated during 3 weeks. Addition of cyclophosphamide marginally increased the remission rate to about 85 per cent. Total tumour doses of less than 35 Gy gave obviously poorer results. The response rate was highest in small cell carcinoma.

A patient with findings of bilateral cortical blindness and a unilateral carotid bruit is reported. A persistent trigeminal artery allowed emboli from a unilateral ulcerated internal carotid plaque to affect the visual cortex bilaterally. The angiographic findings and a brief discussion of this anomalous artery are presented.