Publications by authors named "Chie-Hee Cho"

25 Publications

  • Page 1 of 1

Temperatures in Pigs During 3 T MRI Temperatures, Heart Rates, and Breathing Rates of Pigs During RF Power Deposition in a 3 T (128 MHz) Body Coil.

Bioelectromagnetics 2021 Jan 20;42(1):37-50. Epub 2020 Dec 20.

Institute for Medical Statistics, Programming and Data Science, University Clinic Jena, Jena, Germany.

Exposure to radiofrequency (RF) power deposition during magnetic resonance imaging (MRI) induces elevated body-tissue temperatures and may cause changes in heart and breathing rates, disturbing thermoregulation. Eleven temperature sensors were placed in muscle tissue and one sensor in the rectum (measured in 10 cm depth) of 20 free-breathing anesthetized pigs to verify temperature curves during RF exposure. Tissue temperatures and heart and breathing rates were measured before, during, and after RF exposure. Pigs were placed into a 60-cm diameter whole-body resonator of a 3 T MRI system. Nineteen anesthetized pigs were divided into four RF exposure groups: sham (0 W/kg), low-exposure (2.7 W/kg, mean exposure time 56 min), moderate-exposure (4.8 W/kg, mean exposure time 31 min), and high-exposure (4.4 W/kg, mean exposure time 61 min). One pig was exposed to a whole-body specific absorption rate (wbSAR) of 11.4 W/kg (extreme-exposure). Hotspot temperatures, measured by sensor 2, increased by mean 5.0 ± 0.9°C, min 3.9; max 6.3 (low), 7.0 ± 2.3°C, min 4.6; max 9.9 (moderate), and 9.2 ± 4.4°C, min 6.1, max 17.9 (high) compared with 0.3 ± 0.3°C in the sham-exposure group (min 0.1, max 0.6). Four time-temperature curves were identified: sinusoidal, parabolic, plateau, and linear. These curve shapes did not correlate with RF intensity, rectal temperature, breathing rate, or heart rate. In all pigs, rectal temperatures increased (2.1 ± 0.9°C) during and even after RF exposure, while hotspot temperatures decreased after exposure. When rectal temperature increased by 1°C, hotspot temperature increased up to 42.8°C within 37 min (low-exposure) or up to 43.8°C within 24 min (high-exposure). Global wbSAR did not correlate with maximum hotspot. Bioelectromagnetics. 2021;42:37-50. © 2020 The Authors. Bioelectromagnetics published by Wiley Periodicals LLC on behalf of Bioelectromagnetics Society.
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http://dx.doi.org/10.1002/bem.22311DOI Listing
January 2021

Insight Into the Ontogeny of GnRH Neurons From Patients Born Without a Nose.

J Clin Endocrinol Metab 2020 05;105(5)

Clinical Research Branch, National Institute of Environmental Health Sciences, Durham, North Carolina.

Context: The reproductive axis is controlled by a network of gonadotropin-releasing hormone (GnRH) neurons born in the primitive nose that migrate to the hypothalamus alongside axons of the olfactory system. The observation that congenital anosmia (inability to smell) is often associated with GnRH deficiency in humans led to the prevailing view that GnRH neurons depend on olfactory structures to reach the brain, but this hypothesis has not been confirmed.

Objective: The objective of this work is to determine the potential for normal reproductive function in the setting of completely absent internal and external olfactory structures.

Methods: We conducted comprehensive phenotyping studies in 11 patients with congenital arhinia. These studies were augmented by review of medical records and study questionnaires in another 40 international patients.

Results: All male patients demonstrated clinical and/or biochemical signs of GnRH deficiency, and the 5 men studied in person had no luteinizing hormone (LH) pulses, suggesting absent GnRH activity. The 6 women studied in person also had apulsatile LH profiles, yet 3 had spontaneous breast development and 2 women (studied from afar) had normal breast development and menstrual cycles, suggesting a fully intact reproductive axis. Administration of pulsatile GnRH to 2 GnRH-deficient patients revealed normal pituitary responsiveness but gonadal failure in the male patient.

Conclusions: Patients with arhinia teach us that the GnRH neuron, a key gatekeeper of the reproductive axis, is associated with but may not depend on olfactory structures for normal migration and function, and more broadly, illustrate the power of extreme human phenotypes in answering fundamental questions about human embryology.
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http://dx.doi.org/10.1210/clinem/dgaa065DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7108682PMC
May 2020

Cephalad dislocation of PICCs under different upper limb positions: influence of age, gender, BMI, number of lumens.

J Vasc Access 2018 Mar 19;19(2):141-145. Epub 2018 Feb 19.

1 Institute for Diagnostic and Interventional Radiology, University Clinic Jena, Jena - Germany.

Purpose: To evaluate parameters that influence the amount of movement of peripherally inserted central catheter (PICC) tips regarding upper limb movement.

Methods: In a prospective 12-month observational study, 200 PICCs were implanted in 162 patients (mean age 56.8 ± 15.2 years) by interventional radiologists into the basilic vein of the mid-aspect of the upper arm. Three PICC tip positions were documented with a chest x-ray: patient supine with an abducted (90°), an adducted arm, and in an upright position with an adducted arm. Multivariable analyses were performed, based on the three positions: body mass index (BMI), number of lumens, age, gender, side of the implantation, and brand.

Results: Up to 88% of the PICCs dislocated in a mean of 19 mm cephalad when the patient was positioned from a supine in an upright position. The greatest influence upon dislocation was the position change from supine to upright. The side of the implanted PICC (left vs. right) had no influence.

Conclusions: Cephalad dislocations of mean 19 mm regularly occur in the upright position induced by gravity. This needs to be taken in account and the PICC should be safely positioned one vertebra lower in the superior vena cava superior with a last confirmation of the PICC placement in an upright position.
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http://dx.doi.org/10.5301/jva.5000809DOI Listing
March 2018

Corrigendum: SMCHD1 mutations associated with a rare muscular dystrophy can also cause isolated arhinia and Bosma arhinia microphthalmia syndrome.

Nat Genet 2017 05;49(6):969

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http://dx.doi.org/10.1038/ng0617-969cDOI Listing
May 2017

SMCHD1 mutations associated with a rare muscular dystrophy can also cause isolated arhinia and Bosma arhinia microphthalmia syndrome.

Nat Genet 2017 Feb 9;49(2):238-248. Epub 2017 Jan 9.

Molecular Neurogenetics Unit and Psychiatric and Neurodevelopmental Genetics Unit, Center for Human Genetic Research, Massachusetts General Hospital, Boston, Massachusetts, USA.

Arhinia, or absence of the nose, is a rare malformation of unknown etiology that is often accompanied by ocular and reproductive defects. Sequencing of 40 people with arhinia revealed that 84% of probands harbor a missense mutation localized to a constrained region of SMCHD1 encompassing the ATPase domain. SMCHD1 mutations cause facioscapulohumeral muscular dystrophy type 2 (FSHD2) via a trans-acting loss-of-function epigenetic mechanism. We discovered shared mutations and comparable DNA hypomethylation patterning between these distinct disorders. CRISPR/Cas9-mediated alteration of smchd1 in zebrafish yielded arhinia-relevant phenotypes. Transcriptome and protein analyses in arhinia probands and controls showed no differences in SMCHD1 mRNA or protein abundance but revealed regulatory changes in genes and pathways associated with craniofacial patterning. Mutations in SMCHD1 thus contribute to distinct phenotypic spectra, from craniofacial malformation and reproductive disorders to muscular dystrophy, which we speculate to be consistent with oligogenic mechanisms resulting in pleiotropic outcomes.
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http://dx.doi.org/10.1038/ng.3743DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5473428PMC
February 2017

Analysis of the periimplant tissue of craniofacial implants by sulcus fluid flow rate (SFFR).

J Prosthet Dent 2011 Aug;106(2):87-94

Institute for Diagnostic and Interventional Radiology, University Clinic Jena, Friedrich-Schiller-University, Germany.

Statement Of Problem: The tissue surrounding craniofacial implants is prone to inflammation; however, no adequate instrument is currently available to measure this objectively.

Purpose: The purpose of this study was to describe the parameters influencing the sulcus fluid flow rate in the extraoral periimplant tissue environment.

Material And Methods: Thirty-four patients with 112 craniofacial implants participated. The sulcus fluid flow rate (SFFR) was measured with standardized paper strips. The influence of cleansing liquids, implant location, presence of purulent exudates, smoking habits, depth of crevice, and previous irradiation on the sulcus fluid flow rate were evaluated with covariate adjusted finite mixture models.

Results: Two latent subgroups of SFFR were identified based on a mixed model. The majority (95.5%) had a mean value of 1.44 mm, and the smaller subgroup (4.5%) had a mean value of 10.4 mm. The SFFR values were increased when purulent exudates were present (regression coefficient 1.41), 95% CI (0.67, 2.16). The depth of the crevice influenced the SFFR per unit depth (regression coefficient 0.37), 95% CI (0.22, 0.53). Additional covariates, such as the implant location, history of smoking, and prior irradiation, had no statistical effect on SFFR.

Conclusions: SFFR can be measured objectively in the extraoral periimplant tissue.
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http://dx.doi.org/10.1016/S0022-3913(11)60101-7DOI Listing
August 2011

Long term combination treatment with bevacizumab, pegylated liposomal doxorubicin and regional abdominal hyperthermia in platinum refractory ovarian cancer: a case report and review of the literature.

Anticancer Res 2011 Aug;31(8):2675-7

Department of Gynecology, Charité University Medicine of Berlin, Berlin, Germany.

Background: Platinum resistance constitutes a therapeutic challenge in the treatment of ovarian cancer, with overall unsatisfactory response rates to standard chemotherapy and correspondingly low survival. Regional abdominal hyperthermia and bevacizumab are treatment options that have both shown the capacity to improve the results of standard chemotherapy in the platinum-resistant situation, when added to the treatment schedule.

Case Report: We report on a 29-year-old patient with primary platinum-refractory ovarian cancer, who was treated with a combination of pegylated liposomal doxorubicin, regional abdominal hyperthermia and bevacizumab in a four-week cycle over a long-term period of 38 months. Due to an excellent clinical and radiologic response resulting in stable disease, with a concomitant mild toxicity profile consisting only of intermitted diarrhoea and mild fatigue [corrected] , the treatment was continued in an ambulatory setting.

Discussion: To our knowledge we describe the first experience with combination treatment of pegylated liposomal doxorubicin with regional abdominal hyperthermia and bevacizumab in a long term setting of almost 2 years. Excellent response with comparably low toxicity was demonstrated. Further evaluation as a therapeutic option in this heavily pretreated and highly palliative patient population is warranted.
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August 2011

Percutaneous push-through gastrostomy by applying a CT-guided gastropexy.

J Vasc Interv Radiol 2011 Aug 8;22(8):1149-52. Epub 2011 May 8.

Department of Radiology, Charité University Hospital Berlin, Campus Charité Mitte, Charitéplatz 1, D-10115 Berlin, Germany.

Purpose: To evaluate the feasibility and complications of percutaneous push-through gastrostomy via a computed tomography (CT)--guided gastropexy.

Materials And Methods: From January 2005 to March 2008, 14 patients in whom an oropharyngeal passage with an endoscope was impossible received a gastrostomy using the push-through technique. To attach the stomach against the abdominal wall, a CT-guided gastropexy was performed in all patients before the gastrostomy. The initial gastric tube was replaced with a short, low-profile gastric tube 2 weeks after the gastrostomy procedure. Patients were monitored for complications and survival for 6 months.

Results: The CT-guided dual gastropexy and percutaneous push-through gastrostomy was successfully inserted in all patients. Six months follow-up of the patients revealed only minor complications: one gastrostomy leakage and two local wounds.

Conclusions: CT-guided dual gastropexy combined with the push-type gastrostomy technique is practical and safe in patients in whom an oropharyngeal passage with an endoscope is impossible and represents an alternative method of gastric fixation for radiologically placed gastrostomy tubes.
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http://dx.doi.org/10.1016/j.jvir.2011.02.037DOI Listing
August 2011

Double-lumen central venous port catheters: simultaneous application for chemotherapy and parenteral nutrition in cancer patients.

J Vasc Access 2010 Oct-Dec;11(4):335-41

Department of Radiology, Charité University Medicine, Berlin, Germany.

Purpose: This study was designed to evaluate the clinical benefit of low-profile double-lumen port catheters in patients receiving simultaneous chemotherapy and parenteral nutrition (PN). Potential advantages, complications, and the durations of simultaneous and single use of the catheter were assessed.

Methods: At a university teaching hospital, 10 patients received a double-lumen port catheter (5 men, 5 women; mean age 61.5 ± 12 years). All port implantations were performed under ultrasonographic and fluoroscopic guidance in the radiologic interventional suite. Procedure-related immediate, early, and late complications were recorded until removal of the device, patient's death, or completion of follow-up period. Application times and durations for chemotherapy or PN were determined.

Results: No immediate complications were observed. First use of the port system for chemotherapy was within 12 days (± 25 days, range 0-84 days) and within 17 hours (± 22 hours, range 0-72 hours) for PN on average. During the application of PN, no delay or interruption of chemotherapy was observed. The port catheter was used for the simultaneous application of chemotherapy and PN for a total of 1,216 hours. One port catheter was removed after 30 days due to suspected port infection.

Conclusion: Central venous double-lumen port systems as a therapeutic option in patients requiring chemotherapy and PN can increase safety during those simultaneous applications, while offering improved patient comfort.
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http://dx.doi.org/10.5301/jva.2010.5812DOI Listing
May 2011

Regional abdominal hyperthermia combined with systemic chemotherapy for the treatment of patients with ovarian cancer relapse: Results of a pilot study.

Int J Hyperthermia 2010 ;26(2):118-26

Department of Gynaecology, University Hospital, Berlin, Germany.

Purpose: Due to the poor prognosis of patients with ovarian cancer relapse (OCR), newer strategies are warranted to improve the therapeutic index. We performed a prospective phase I/II-study of regional abdominal hyperthermia (RHT) combined with systemic chemotherapy in OCR patients in order to evaluate outcome, efficacy and tolerance.

Materials And Methods: OCR patients with an Eastern Cooperative Oncology Group status <2, without any thromboembolic disease or severe cardiovascular co-morbidities, and pre-treated with at least one systemic chemotherapy regimen due to epithelial ovarian cancer were enrolled into the present study. RHT was applied using a SIGMA 60 applicator and a Hybrid-System SIGMA-Eye/MRT composed of a 1.5T-MRT and a Sigma-Eye-applicator.

Results: Overall, 36 OCR patients were enrolled. The majority of the patients (>80%) were classified as platinum resistant. The most common chemotherapeutic agent applied was pegylated-liposomal-doxorubicin (47.2%) followed by carboplatin (16.6%) and topotecan (13.9%). One patient (2.8%) achieved a complete remission (CR), 12 patients (33.3%) yielded a partial remission (PR) and 16 patients (44.4%) developed a progressive disease (PD). In platinum-sensitive patients we observed higher response (57.1% versus 31%) and lower progression rates (28.6% versus 48.3%) than in platinum-resistant patients. Eleven patients (30.5%) discontinued treatment due to toxicity. The main toxicity was a haematological one with grade 3/4 anaemia, leucopenia and thrombocytopenia occurring in 13.9%, 5.6% and 8.3%, respectively. Median overall survival was 12 months (range: 1-48), while median progression-free survival was 5 months (range: 0.5-34).

Conclusions: Our results demonstrate the feasibility of RHT combined with systemic treatment. Prospective phase III trials are warranted to evaluate the benefit and efficacy in heavily pre-treated patients with OCR.
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http://dx.doi.org/10.3109/02656730903369200DOI Listing
April 2010

A comparison of clinical outcomes with regular- and low-profile totally implanted central venous port systems.

Cardiovasc Intervent Radiol 2009 Sep 16;32(5):975-9. Epub 2008 Dec 16.

Department of Radiology, Charité Campus Mitte, Charitéplatz 1, Berlin, Germany.

The purpose of this study was to evaluate whether low-profile totally implanted central venous port systems can reduce the late complication of skin perforation. Forty patients (age, 57 +/- 13 years; 22 females, 18 males) were randomized for the implantation of a low-profile port system, and another 40 patients (age, 61 +/- 14 years; 24 females, 16 males) received a regular port system as control group. Indications for port catheter implantation were malignant disease requiring chemotherapy. All port implantations were performed in the angiography suite using sonographically guided central venous puncture and fluoroscopic guidance of the catheter placement. Procedure time, number of complications (procedure-related immediate, early, and late complications), and number of explantations were assessed. Follow-up was performed for 6 months. All port implantations were successfully completed in both study groups. There were two incidents of skin perforation observed in the control group. One skin perforation occurred 13 weeks and the other 16 weeks after port implantation (incidence, 5%) in patients with regular-profile port systems. Two infections were observed, one port infection in each study group. Both infections were characterized as catheter-related infections (infection rate: 0.15 catheter-related infections per 1000 catheter days). In conclusion, low-profile port systems can be placed as safely as traditional chest ports and reduce the risk of developing skin perforations, which occurs when the port system is too tight within the port pocket.
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http://dx.doi.org/10.1007/s00270-008-9477-3DOI Listing
September 2009

Amelanotic metastasis of melanoma mimicking ovarian cancer: a case report and review of the literature.

Anticancer Res 2008 Jan-Feb;28(1B):563-6

Department of Gynecology and Obstetrics, Charité/Campus Virchow-Klinikum, University Medicine of Berlin, Augustenburger Platz 1, 13353 Berlin, Germany.

Ovarian manifestation of metastatic amelanotic melanoma is exceptionally rare and can lead to the clinical and even histological misdiagnosis of ovarian cancer. We report on a 35-year-old female patient who presented with bilateral adnexal masses, as well as massive ascites. She underwent laparascopy and multiple biopsies were taken. She was histologically diagnosed with malignant ovarian tumour and was referred for radical surgery. Postoperative final histological examination and immunohistochemical staining of the tumour revealed an amelanotic epithelioid melanoma. Despite the variety of this case, clinicians should be aware of this differential diagnosis when treating ovarian cancer. This report discusses the differential diagnosis and clinical management of both metastatic amelanotic malignant melanoma of the ovary and epithelial ovarian cancer.
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April 2008

Postimplantation analysis enables improvement of dose-volume histograms and reduction of toxicity for permanent seed implantation.

Int J Radiat Oncol Biol Phys 2008 May 26;71(1):28-35. Epub 2007 Nov 26.

Department of Radiation Oncology, Charité Universitätsmedizin Berlin, Berlin, Germany.

Purpose: To demonstrate how postimplantation analysis is useful for improving permanent seed implantation and reducing toxicity.

Patients And Methods: We evaluated 197 questionnaires completed by patients after permanent seed implantation (monotherapy between 1999 and 2003). For 70% of these patients, a computed tomography was available to perform postimplantation analysis. The index doses and volumes of the dose-volume histograms (DVHs) were determined and categorized with respect to the date of implantation. Differences in symptom scores relative to pretherapeutic status were analyzed with regard to follow-up times and DVH descriptors. Acute and subacute toxicities in a control group of 117 patients from an earlier study (June 1999 to September 2001) by Wust et al. (2004) were compared with a matched subgroup from this study equaling 110 patients treated between October 2001 and August 2003.

Results: Improved performance, identifying a characteristic time dependency of DVH parameters (after implantation) and toxicity scores, was demonstrated. Although coverage (volume covered by 100% of the prescription dose of the prostate) increased slightly, high-dose regions decreased with the growing experience of the users. Improvement in the DVH and a reduction of toxicities were found in the patient group implanted in the later period. A decline in symptoms with follow-up time counteracts this gain of experience and must be considered. Urinary and sexual discomfort was enhanced by dose heterogeneities (e.g., dose covering 10% of the prostate volume, volume covered by 200% of prescription dose). In contrast, rectal toxicities correlated with exposed rectal volumes, especially the rectal volume covered by 100% of the prescription dose.

Conclusion: The typical side effects occurring after permanent seed implantation can be reduced by improving the dose distributions. An improvement in dose distributions and a reduction of toxicities were identified with elapsed time between 1999 and 2003.
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http://dx.doi.org/10.1016/j.ijrobp.2007.09.011DOI Listing
May 2008

[Thermal therapy of prostate cancer using magnetic nanoparticles].

Actas Urol Esp 2007 Jun;31(6):660-7

Department of Urology, Campus Mitte, Charité-Universitätsmedizin Berlin, Alemania.

A novel method of interstitial heating using magnetic nanoparticles and a direct injection technique has been evaluated in human cancers in recent clinical trials. In prostate cancer, this approach was investigated in two separate phase-I-studies, employing magnetic nanoparticle thermotherapy alone and in combination with permanent seed brachytherapy. The feasibility and good tolerability was shown in both trials, using the first prototype of a magnetic field applicator. As with any other heating technique, this novel approach requires specific tools for planning, quality control and thermal monitoring, based on appropriate imaging and modelling techniques. In these first clinical trials, a newly developed method for planning and non-invasive calculations of the 3-dimensional temperature distribution based on computed tomography could be validated. Limiting factors of this approach at present are patient discomfort at high magnetic field strengths and suboptimal intratumoral distribution of nanoparticles. Until these limitations will be overcome and thermal ablation can safely be applied as a monotherapy, this treatment modality is being evaluated in combination with irradiation in patients with localized prostate cancer.
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http://dx.doi.org/10.1016/s0210-4806(07)73703-8DOI Listing
June 2007

Simulation of different applicator positions for treatment of a presacral tumour.

Int J Hyperthermia 2007 Feb;23(1):37-47

Clinic for Radiation Medicine, Charité Medical School, Campus Berlin Buch, Lindenberger Weg 80, 13125 Berlin, Germany.

Introduction: Proximally located presacral recurrences of rectal carcinomas are known to be difficult to heat due to the complex anatomy of the pelvis, which reflect, shield and diffract the power. This study is to clarify whether a change of position of the Sigma-Eye applicator in this region can improve the heating.

Material And Methods: Finite element (FE) planning calculations were made for a phantom model with a proximal presacral tumour using a fixed 100 MHz radiofrequency radiation. Shifts of the applicator were simulated in 1 cm steps in x-(lateral), y-(posterior) and z-(longitudinal) direction. Computations also considered the network effects of the Sigma-Eye applicator. Optimisation of the phases and amplitudes for all positions were performed after solving the bioheat-transfer-equation. The parameters T90, T50, sensitivity, hot spot volume and total deposited power have been sampled for every applicator position with optimised plans and a standard plan.

Results: The ability to heat a presacral tumour clearly depends on the applicator position, for standard antenna adjustment and also for optimised steering of the Sigma-Eye applicator. The gamma-direction (anterior-posterior) is very sensitive. Using optimised steering for each position, in z-direction (longitudinal), we found an unexpected additional optimum at 8 cm cranial from the middle position of the phantom. The x-direction (lateral) is in a clinical setting less important and shows only smaller changes of T90 with an expected optimum in the central position. A positioning of the applicator in the axial and anterior position of the mid-pubic symphysis should be avoided for treatment of the presacral region, regardless of the used adjustment. Use of amplitude and phase optimisation yields better T90 values than plans optimised only by phases, but they are much more sensitive for small variations of phases and amplitudes during a treatment, and the total power of the Sigma-Eye applicator can be restricted by the treatment software.

Conclusions: Complex geometry of the human pelvis seems to be the reason for the difficulties to warm up the proximal presacral region. The assumption that every position can be balanced by a proper phase adaption, is true only in a small range. A centring of the applicator on the mid-pubic symphysis to heat this region should be avoided. From the practical point of view improved warming should be performed by optimisation of phases only.
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http://dx.doi.org/10.1080/02656730601121549DOI Listing
February 2007

Thermotherapy of prostate cancer using magnetic nanoparticles: feasibility, imaging, and three-dimensional temperature distribution.

Eur Urol 2007 Dec 17;52(6):1653-61. Epub 2006 Nov 17.

Department of Urology, Campus Mitte, Charité-Universitätsmedizin, Berlin, Germany.

Objectives: To investigate the feasibility of thermotherapy using biocompatible superparamagnetic nanoparticles in patients with locally recurrent prostate cancer and to evaluate an imaging-based approach for noninvasive calculations of the three-dimensional temperature distribution.

Methods: Ten patients with locally recurrent prostate cancer following primary therapy with curative intent were entered into a prospective phase 1 trial. The magnetic fluid was injected transperineally into the prostates according to a preplan. Patients received six thermal therapies of 60-min duration at weekly intervals using an alternating magnetic field applicator. A method of three-dimensional thermal analysis based on computed tomography (CT) of the prostates was developed and correlated with invasive and intraluminal temperature measurements. The sensitivity of nanoparticle detection by means of CT was investigated in phantoms.

Results: The median detection rate of iron oxide nanoparticles in tissue specimens using CT was 89.5% (range: 70-98%). Maximum temperatures up to 55 degrees C were achieved in the prostates. Median temperatures in 20%, 50%, and 90% of the prostates were 41.1 degrees C (range: 40.0-47.4 degrees C), 40.8 degrees C (range: 39.5-45.4 degrees C), and 40.1 degrees C (range: 38.8-43.4 degrees C), respectively. Median urethral and rectal temperatures were 40.5 degrees C (range: 38.4-43.6 degrees C) and 39.8 degrees C (range: 38.2-43.4 degrees C). The median thermal dose was 7.8 (range: 3.5-136.4) cumulative equivalent minutes at 43 degrees C in 90% of the prostates.

Conclusion: The heating technique using magnetic nanoparticles was feasible. Hyperthermic to thermoablative temperatures were achieved in the prostates at 25% of the available magnetic field strength, indicating a significant potential for higher temperatures. A noninvasive thermometry method specific for this approach could be developed, which may be used for thermal dosimetry in future studies.
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http://dx.doi.org/10.1016/j.eururo.2006.11.023DOI Listing
December 2007

Radiochemotherapy combined with regional pelvic hyperthermia induces high response and resectability rates in patients with nonresectable cervical cancer > or =FIGO IIB "bulky".

Int J Radiat Oncol Biol Phys 2006 Nov 18;66(4):1159-67. Epub 2006 Sep 18.

Clinic for Radiation Medicine, Campus Virchow-Klinikum, Charité Univesitätsmedizin, Berlin, Germany.

Purpose: To evaluate preoperative radiochemotherapy combined with regional pelvic hyperthermia in patients with nonresectable cervical cancer >/= International Federation of Gynecology and Obstetrics (FIGO) IIB "bulky" in a Phase II study.

Methods And Materials: Thirty-two patients with nonresectable FIGO IIB-IVA cervical cancer confined to the pelvis were treated with radiochemotherapy (5 x 1.8 Gy/wk, 45-50.4 Gy; cisplatin, 40 mg/m2/wk) and weekly regional pelvic hyperthermia (SIGMA-60 applicator, system BSD-2000; BSD Medical Corp., Salt Lake City, UT). Responders underwent hysterectomy if possible, whereas patients still unresectable received definitive hyperthermic radiochemotherapy. Feasibility, toxicity, as well as response and resectability, local progression free- and overall survival rates, were evaluated.

Results: Thirty of 32 patients completed treatment. Grade III/IV toxicities (National Cancer Institute-Common Toxicity Criteria) were diarrhea (n = 5), weight loss >10 kg (n = 4), and nausea (n = 2). Twenty-four of 32 patients (75%) achieved a partial remission after 45-50 Gy, and 20 patients underwent hysterectomy (18 patients, R0; 8 patients pCR). Three-year overall survival was 60%, with moderate (13%) rates of severe late toxicity. R0-resected patients had a favorable chronic toxicity profile and an excellent prognosis (3-year survival rate: 93%). Response depended on thermal parameters (vaginal reference point), whereas response, R0-resection, and FIGO stage are significant prognostic factors for survival.

Conclusion: Preoperative hyperthermic radiochemotherapy (45-50 Gy) induces high response rates and enables curative surgery in a high proportion of patients with nonresectable cervical cancer. Therefore, the use of hyperthermia in conjunction with standard chemo-/radiotherapy +/- surgery may allow for more effective tumor treatment while decreasing the risk of complications in patients with locally advanced cervical cancer.
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http://dx.doi.org/10.1016/j.ijrobp.2006.06.052DOI Listing
November 2006

Thermal monitoring: invasive, minimal-invasive and non-invasive approaches.

Int J Hyperthermia 2006 May;22(3):255-62

Clinic for Radiation Medicine, Charité Medical School, Campus Virchow Klinikum, Berlin, Germany.

Background: Thermal treatments need verification of effectiveness. Invasive intra-tumoural thermometry was established as a standard method several years ago. However, in deep heating, invasive techniques have disadvantages. Therefore, alternatives have been suggested and are under development.

Methods: In three phase II studies treating rectal cancer, cervical cancer and prostate cancer, this study replaced invasive (intra-tumoural) thermometry by tumour-related reference points or catheter sections in the rectum, vagina or urethra. Index temperatures and thermal dose parameters were determined. Two recent studies treated patients with recurrent rectal cancer and soft tissue sarcoma using non-invasive MR-thermometry employing the SIGMA-Eye applicator. The proton resonance frequency shift (PRFS) method was employed to generate MR-temperature distributions during the entire heat treatment in 10 min intervals (via phase differences). Fat correction (nulling specified regions in the fat tissue) was utilized to calibrate the method, in particular with respect to the B0-drift.

Results: Statistically significant correlations were found between response (downstaging, WHO) and thermal parameters in rectal cancer (37 patients, rectum measurement, T90, cum min T90 >or= 40.5 degrees C) and cervical cancer (30 patients, vagina, mean temperature and equ min 43 degrees C in a reference point). In prostate cancer (14 patients), a clear correlation was verified between long-term PSA control (or= 40.5 degrees C). The mean MR-temperature in the tumour at steady-state as well as the mean T90 were significantly correlated with response for recurrent rectal carcinoma regarding palliation and analgesia (15 patients) and with pathohistological regression rate in soft tissue sarcoma (nine patients).

Conclusions: For tumours in the pelvis and in the lower extremities, invasive measurements can be replaced by minimally-invasive or non-invasive techniques, which provide equivalent or even more complete information. Extending the application of these surveillance methods to abdominal tumours or liver metastases is a challenge, but strongly desirable for clinical reasons.
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http://dx.doi.org/10.1080/02656730600661149DOI Listing
May 2006

In vivo assessment of the tolerance dose of small liver volumes after single-fraction HDR irradiation.

Int J Radiat Oncol Biol Phys 2005 Jul;62(3):776-84

Klinik für Strahlenheilkunde, Charité, Campus Virchow-Klinikum, Humboldt-University Medical School, Berlin, Germany.

Purpose: To prospectively assess a dose-response relationship for small volumes of liver parenchyma after single-fraction irradiation.

Methods And Materials: Twenty-five liver metastases were treated by computed tomography (CT)-guided interstitial brachytherapy. Magnetic resonance imaging was performed 1 day before and 3 days and 6, 12, and 24 weeks after therapy. MR sequences included T1-w gradient echo (GRE) enhanced by hepatocyte-targeted gadobenate dimeglumine. All MRI data sets were merged with 3D dosimetry data and evaluated by two radiologists. The reviewers indicated the border of hyperintensity on T2-w images (edema) or hypointensity on T1-w images (loss of hepatocyte function). Based on the total 3D data, a dose-volume histogram was calculated. We estimated the threshold dose for either edema or function loss as the D(90), i.e., the dose achieved in at least 90% of the pseudolesion volume.

Results: Between 3 days and 6 weeks, the extension of the edema increased significantly from the 12.9 Gy isosurface to 9.9 Gy (standard deviation [SD], 3.3 and 2.6). No significant change was detected between 6 and 12 weeks. After 24 weeks, the edematous tissue had shrunk significantly to 14.7 Gy (SD, 4.2). Three days postbrachytherapy, the D(90) for hepatocyte function loss reached the 14.9 Gy isosurface (SD, 3.9). At 6 weeks, the respective zone had increased significantly to 9.9 Gy (SD, 2.3). After 12 and 24 weeks, the dysfunction volume had decreased significantly to the 11.9 Gy and 15.2 Gy isosurface, respectively (SD, 3 and 4.1).

Conclusions: The 95% interval from 7.6 to 12.2 Gy found as the minimal hepatocyte tolerance after 6 weeks accounts for the radiobiologic variations found in CT-guided brachytherapy, including heterogeneous dose rates by variable catheter arrays.
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http://dx.doi.org/10.1016/j.ijrobp.2004.11.022DOI Listing
July 2005

Liver malignancies: CT-guided interstitial brachytherapy in patients with unfavorable lesions for thermal ablation.

J Vasc Interv Radiol 2004 Nov;15(11):1279-86

Klinik für Strahlenheilkunde, Charité Virchow-Klinikum, Augustenburger Platz 1, 13353 Berlin, Germany.

Purpose: To evaluate computed tomography (CT)-guided brachytherapy in patients with very large liver malignancies or with liver tumors located adjacent to the liver hilum.

Materials And Methods: In this prospective nonrandomized phase II trial, we treated 20 patients (19 liver metastases and one cholangiocarcinoma) with CT-guided high-dose-rate (HDR) brachytherapy using a (192) Iridium source. All patients demonstrated no functional liver degradation prior to irradiation. Entry criteria were liver tumors > 5 cm (group A, n = 11, no upper limit) or liver tumors < or = 5 cm adjacent to the liver hilum (group B, n = 9). Dose planning for brachytherapy was performed with three dimensional (3D) CT data acquired after percutaneous applicator positioning. Magnetic resonance (MR) imaging follow-up was performed 6 weeks and every 3 months post intervention. Primary endpoints were complications, local tumor control (absence of tumor growth after treatment followed by shrinkage of the lesion starting at 6 months) and progression-free survival.

Results: The mean tumor diameter was 7.7 cm (range, 5.5-10.8 cm) in group A, 3.6 cm (range, 2.2-4.9 cm) in group B. On average, a minimal dose of 17 Gy in the target volume was applied (range, 12-25 Gy). Severe side effects were recorded in two patients (10%). One patient demonstrated an obstructive jaundice caused by tumor edema after irradiation of a metastasis adjacent to the bile duct bifurcation. One patient developed intra-abdominal hemorrhage that was treated by a single blood transfusion and has ceased. We frequently encountered moderate increases of liver enzymes (70% of patients) and bilirubin (50% of patients) without clinical symptoms and thus considered to be insignificant. The median follow-up was 13 months. In group A (tumors > 5 cm), primary local tumor control after 6 and 12 months was 74% and 40%, respectively; in group B, it was 100% and 71%, respectively. All but one local recurrence (in a patient with diffuse tumor progression) were successfully treated during another CT-guided brachytherapy leading to a primary assisted local control of 93% after 12 months.

Conclusion: CT-guided brachytherapy based on individual dose plans and 3D CT data sets generated encouraging results in large liver malignancies as well as in tumors located adjacent to the liver hilum.
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http://dx.doi.org/10.1097/01.RVI.0000141343.43441.06DOI Listing
November 2004

[CT-Guided brachytherapy. A novel percutaneous technique for interstitial ablation of liver metastases].

Strahlenther Onkol 2004 May;180(5):274-80

Klinik für Strahlenheilkunde, Charité Virchow-Klinikum, Humboldt-Universität zu Berlin, Berlin, Germany.

Purpose: To assess safety and efficacy of CT-guided brachytherapy of liver malignancies.

Patients And Methods: 21 patients with 21 liver malignancies (19 metastases, two primary liver tumors) were treated with interstitial CT-guided brachytherapy applying a (192)Ir source. In all patients, the use of image-guided thermal tumor ablation such as by radiofrequency or laser-induced thermotherapy (LITT) was impeded either by tumor size > or = 5 cm in seven, adjacent portal or hepatic vein in ten, or adjacent bile duct bifurcation in four patients. Dosimetry was performed using three-dimensional CT data sets acquired after CT-guided positioning of the brachytherapy catheters.

Results: The mean tumor diameter was 4.6 cm (2.5-11 cm). The mean minimal tumor dose inside the tumor margin amounted to 17 Gy (12-20 Gy). The proportion of the liver parenchyma exposed to > 5 Gy was 18% (5-39%) of total liver parenchyma minus tumor volume. Nausea and vomiting were observed in six patients after brachytherapy (28%). One patient demonstrated obstructive jaundice due to tumor edema after irradiation of a metastasis adjacent to the bile duct bifurcation. We commonly encountered asymptomatic increases of liver enzymes. Local control rates after 6 and 12 months were 87% and 70%, respectively.

Conclusion: CT-guided brachytherapy is safe and effective. This technique displays broader indications compared to image-guided thermal ablation by radiofrequency or LITT with respect to tumor size or localization.
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http://dx.doi.org/10.1007/s00066-004-1179-4DOI Listing
May 2004

CT-guided interstitial brachytherapy of liver malignancies alone or in combination with thermal ablation: phase I-II results of a novel technique.

Int J Radiat Oncol Biol Phys 2004 Apr;58(5):1496-505

Klinik für Strahlenheilkunde, Charité Virchow-Klinikum Medical Faculty of the Humboldt-University Berlin, Berlin, Germany.

Purpose: To assess the safety and efficacy of CT-guided brachytherapy alone or in combination with laser-induced thermotherapy (LITT) in patients with liver malignancies.

Methods And Materials: Thirty-seven patients presented with 36 liver metastases and two primary liver carcinomas. Twenty-one patients were treated with CT-guided high-dose-rate brachytherapy alone using a 192Ir source. Sixteen patients received brachytherapy directly after MRI-guided LITT. The indications for brachytherapy alone were a tumor size >5 cm, adjacent central bile duct or adjacent major vessels causing unfavorable cooling effects for thermal ablation, and technical failures of LITT. The dosimetry for brachytherapy was performed using three-dimensional CT data acquired after percutaneous applicator positioning. On average, a minimal dose of 17 Gy inside the tumor margin was applied (range, 10-20 Gy).

Results: The mean tumor size was 4.6 cm (range, 2.5-11 cm). The mean liver volume receiving > or =5 Gy was 16% (range, 2-40%) of the total liver. Severe complications were recorded in 2 patients (5%). One patient developed acute liver failure possibly related to accidental continuation of oral capecitabine treatment. Another patient demonstrated obstructive jaundice owing to tumor edema after irradiation of a metastasis adjacent to the bile duct bifurcation. A commonly encountered moderate increase of liver enzymes was greatest in patients with combined treatment. The local control rate after 6 months was 73% and 87% for combined treatment and brachytherapy alone, respectively.

Conclusion: CT-guided brachytherapy using three-dimensional CT data for dosimetry is safe and effective alone or in combination with LITT. Brachytherapy as a stand-alone treatment displayed genuine advantages over thermal tumor ablation.
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http://dx.doi.org/10.1016/j.ijrobp.2003.09.024DOI Listing
April 2004

CT-guided transgluteal drainage of deep pelvic abscesses: indications, technique, procedure-related complications, and clinical outcome.

Radiographics 2002 Nov-Dec;22(6):1353-67

Department of Radiology, Massachusetts General Hospital, 55 Fruit St, Boston, MA 02114, USA.

Deep pelvic abscesses may present a unique challenge for percutaneous drainage because of numerous overlying structures, which preclude safe percutaneous access. These structures include the pelvic bones, intestine, bladder, iliac vessels, and gynecologic organs. Use of the transgluteal approach to drain these abscesses can circumvent these obstacles and provide a useful surgical alternative or a temporizing measure. The transgluteal approach requires a thorough understanding of the anatomy of the sciatic foramen region and associated anatomic structures. The ideal approach for transgluteal access is to insert the catheter as close to the sacrum as possible, at the level of the sacrospinous ligament. Transgluteal drainage can be performed with the tandem-trocar technique or the Seldinger technique. Modifications of the procedure are needle aspiration not followed by catheter placement, use of the angled gantry technique, bilateral transgluteal drainage, combined anterior and posterior drainage, and drainage of necrotic pelvic masses. The transgluteal approach is a useful option in pediatric patients. Daily catheter care is essential for successful percutaneous catheter therapy. Although pain has been cited as a common complication of the technique, this complication can be minimized with judicious use of analgesia and a meticulous technique. Other complications are hemorrhage and catheter malposition.
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http://dx.doi.org/10.1148/rg.226025039DOI Listing
January 2003