Moderate-to-deep sedation technique, using propofol and ketamine, allowing synchronised breathing for magnetic resonance high-intensity focused ultrasound (MR-HIFU) treatment for uterine fibroids: a pilot study

BACKGROUND: Magnetic resonance high-intensity focused ultrasound (MR-HIFU) treatment for uterine fibroids is rapidly gaining popularity as a treatment modality. This procedure is generally uncomfortable, painful, and requires minimal or absence of movement and an MR-HIFU synchronised breathing pattern of the patient. Procedural sedation and analgesia protocols have become the standard practice in interventional radiology departments worldwide. The aim of this study was to explore if a sedation regimen with low-dose propofol and ketamine performed by trained non-medical sedation practitioners could result in relief of discomfort for the patient and in adequate working conditions for MR-HIFU treatment for uterine fibroids. METHODS: In this study, conducted from August 2013 until November 2014, 20 patients were subjected to MR-HIFU treatment of uterine fibroids. Patients were deeply sedated using intravenous propofol and esketamine according to a standardised hospital protocol to allow synchronisation of the breathing pattern to the MR-HIFU. The quality of sedation for MR-HIFU and complications were recorded and analysed. The side effects of the sedation technique, the propofol and esketamine consumption rate, the duration of recovery, and patient satisfaction after 24 h were examined. RESULTS: A total of 20 female patients (mean age 42.4 [range 32-53] years) were enrolled. Mean propofol/esketamine dose was 1309 mg/39.5 mg (range 692-1970 mg/ 23.6-87.9 mg). Mean procedure time was 269 min (range 140-295 min). Application of the sedation protocol resulted in a regular breathing pattern, which could be synchronised with the MR-HIFU procedures without delay. The required treatment was completed in all cases. There were no major adverse events. Hypoxemia (oxygen desaturation <92%) and hallucinations were not observed. CONCLUSIONS: The use of a specific combination of IV propofol and esketamine for procedural sedation and analgesia reduced the discomfort and pain during MR-guided HIFU treatments of uterine fibroids. The resulting regular breathing pattern allowed for easy synchronisation of the MR-HIFU procedure. Based on our results, esketamine and propofol sedation performed by trained non-medical sedation practitioners is feasible and safe, has a low risk of major adverse events, and has a short recovery time, avoiding a session of general anaesthesia

Magnetic Resonance-Guided High Intensity Focused Ultrasound Ablation of Breast Cancer

This chapter describes several aspects of MR-HIFU treatment for breast cancer. The current and future applications, technical developments and clinical results are discussed. MR-HIFU ablation is under investigation for the treatment of breast cancer, but is not yet ready for clinical implementation. Firstly, the efficacy of MR-HIFU ablation should be investigated in large trials. The existing literature shows that results of initial, small studies are moderate, but opportunities for improvement are available. Careful patient selection, taking treatment margins into account and using a dedicated breast system might improve treatment outcomes. MRI-guidance has proven to be beneficial for the accuracy and safety of HIFU treatments because of its usefulness before, during and after treatments. In conclusion, MR-HIFU is promising for the treatment of breast cancer and might lead to a change in breast cancer care in the future

REDOX PROPERTIES OF THE METAL CENTERS IN THE MEMBRANE-BOUND HYDROGENASE FROM ALCALIGENES-EUTROPHUS CH34

KNUTTEL K, Schneider K, ERKENS A, et al. REDOX PROPERTIES OF THE METAL CENTERS IN THE MEMBRANE-BOUND HYDROGENASE FROM ALCALIGENES-EUTROPHUS CH34. BULLETIN OF THE POLISH ACADEMY OF SCIENCES-CHEMISTRY. 1994;42(4):495-511.For highly active preparations of the membrane-bound, respiratory chain-linked hydrogenase from Alcaligenes eutrophus strains H16 and CH34, 0.7 moles of nickel and approximately 10 moles of iron per mole of enzyme were determined. The hydrogenase isolated from A. eutrophus CH34, displayed the highest specific activity (540 U/mg protein) and the most intense Ni signals and was therefore used to study the redox properties of the metal centres present in this type of hydrogenase. At 80 K two well-resolved Ni spectra were detected in the course of a redox titration (at pH 7.0): one displayed a Ni-B type signal at g = 2.30, 2.17 and 2.01 representing the Ni(III) centre in the ''ready state'' of the enzyme (''active'' protein conformation, oxidized catalytic centre), the other one consisted of a Ni-C type signal at g = 2.20, 2.16 and 2.01 apparently representing monovalent nickel in the ''active state'' of the enzyme (''active'' protein conformation, reduced catalytic centre) and a minor proportion of a second Ni-C signal (g = 2.31, 2.12, 2.05) induced by the influence of normal daylight. The midpoint potentials determined are -30 mV for Ni(III), -260 mV (appearance of the Ni-C signal) and -340 mV (disappearance of the Ni-C signal) for apparent Ni(I). The midpoint potentials calculated for the FeS clusters are: + 100 mV ([3Fe-4S]1+/0), + 50 m V ([4Fe-4S]2+/1+ cluster I) and -80 mV ([4Fe-4S]2+/1+ cluster II)

Histopathology of breast cancer after magnetic resonance-guided high-intensity focused ultrasound and radiofrequency ablation

AIMS: Magnetic resonance-guided high-intensity focused ultrasound (MR-HIFU) ablation and radiofrequency ablation (RFA) are being researched as possible substitutes for surgery in breast cancer patients. The histopathological appearance of ablated tissue has not been studied in great detail. This study aimed to compare histopathological features of breast cancer after MR-HIFU ablation and RFA. METHODS AND RESULTS: MR-HIFU ablation and RFA were performed in- and ex-vivo. Tumours in six mastectomy specimens were partially ablated with RFA or MR-HIFU. In-vivo MR-HIFU ablation was performed 3-6 days before excision; RFA was performed in the operation room. Tissue was fixed in formalin and processed to haematoxylin and eosin (H&E) and cytokeratin-8 (CK-8)-stained slides. Morphology and cell viability were assessed. Ex-vivo ablation resulted in clear morphological changes after RFA versus subtle differences after MR-HIFU. CK-8 staining was decreased or absent. H&E tended to underestimate the size of thermal damage. In-vivo MR-HIFU resulted in necrotic-like changes. Surprisingly, some ablated lesions were CK-8-positive. Histopathology after in-vivo RFA resembled ex-vivo RFA, with hyper-eosinophilic stroma and elongated nuclei. Lesion borders were sharp after MR-HIFU and indistinct after RFA. CONCLUSION: Histopathological differences between MR-HIFU-ablated tissue and RF-ablated tissue were demonstrated. CK-8 was more reliable for cell viability assessment than H&E when used directly after ablation, while H&E was more reliable in ablated tissue left in situ for a few days. Our results contribute to improved understanding of histopathological features in breast cancer lesions treated with minimally invasive ablative techniques

Meta-analysis of the concordance of histological grade of breast cancer between core needle biopsy and surgical excision specimen

Background With the increasing use of neoadjuvant chemotherapy and minimally invasive ablative therapy in breast cancer, pretreatment assessment of tumour grade on core needle biopsy (CNB) is increasingly needed. However, grading on CNB is possibly less accurate than grading based on the surgical excision specimen. A systematic review and meta-analysis of the literature was conducted to derive a reliable estimate of the agreement in tumour grading between CNB and subsequent surgical excision. Methods Following the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) criteria, Embase, PubMed and the Cochrane Library were searched. Pooled proportions of agreement in grading between CNB and the excision specimen, Cohen's κ and percentages of overestimation and underestimation were calculated. Random-effects models were applied because of substantial heterogeneity, assessed by I2 test. Determinants of the level of agreement in grading were explored with meta-regression. Results Thirty-four articles were included in the systematic review (6029 patients) and 33 in the meta-analysis (4980 patients). Pooled agreement and κ were 71·1 (95 per cent c.i. 68·8 to 73·3) per cent and 0·54 (0·50 to 0·58) respectively. Underestimation and overestimation occurred in 19·1 (17·1 to 21·3) and 9·3 (7·7 to 11·4) per cent respectively. Meta-regression showed associations between agreement of histological type (positive association) and proportion of patients with oestrogen receptor-positive disease (negative association) and grade agreement. Conclusion Grading on CNB corresponds moderately with grading based on excision specimens, with underestimation in about one in five patients. Incorrect CNB tumour grading has limited clinical implications, as multiple factors influence decision-making for adjuvant systemic therapy

Prediction Model For Extensive Ductal Carcinoma In Situ Around Early-Stage Invasive Breast Cancer

OBJECTIVES: Ductal carcinoma in situ (DCIS) is a risk factor for incomplete resection of breast cancer. Especially, extensive DCIS (E-DCIS) or extensive intraductal component often results in positive resection margins. Detecting DCIS around breast cancer before treatment may therefore alter surgery. The purpose of this study was to develop a prediction model for E-DCIS around early-stage invasive breast cancer, using clinicohistopathological and dynamic contrast-enhanced magnetic resonance imaging (MRI) features. MATERIALS AND METHODS: Dynamic contrast-enhanced MRI and local excision were performed in 322 patients with 326 ductal carcinomas. Tumors were segmented from dynamic contrast-enhanced MRI, followed by 3-dimensional extension of the margins with 10 mm. Amount of fibroglandular tissue (FGT) and enhancement features in these extended margins were automatically extracted from the MRI scans. Clinicohistopathological features were also obtained. Principal component analysis and multivariable logistic regression were used to develop a prediction model for E-DCIS. Discrimination and calibration were assessed, and bootstrapping was applied for internal validation. RESULTS: Extensive DCIS occurred in 48 (14.7%) of 326 tumors. Incomplete resection occurred in 56.3% of these E-DCIS-positive versus 9.0% of E-DCIS-negative tumors (P < 0.001). Five components with eigenvalue exceeding 1 were identified; 2 were significantly associated with E-DCIS. The first, positively associated, component expressed early and overall enhancement in the 10-mm tissue margin surrounding the MRI-visible tumor. The second, positively associated, component expressed human epidermal growth factor receptor 2 and amount of FGT around the MRI-visible tumor. The area under the curve value was 0.79 (0.76 after bootstrapping). CONCLUSIONS: Human epidermal growth factor receptor 2 status, early and overall enhancement in the 10-mm margin around the MRI-visible tumor, and amount of FGT in the 10 mm around the MRI-visible tumor were associated with E-DCIS

Prediction Model For Extensive Ductal Carcinoma In Situ Around Early-Stage Invasive Breast Cancer

OBJECTIVES: Ductal carcinoma in situ (DCIS) is a risk factor for incomplete resection of breast cancer. Especially, extensive DCIS (E-DCIS) or extensive intraductal component often results in positive resection margins. Detecting DCIS around breast cancer before treatment may therefore alter surgery. The purpose of this study was to develop a prediction model for E-DCIS around early-stage invasive breast cancer, using clinicohistopathological and dynamic contrast-enhanced magnetic resonance imaging (MRI) features. MATERIALS AND METHODS: Dynamic contrast-enhanced MRI and local excision were performed in 322 patients with 326 ductal carcinomas. Tumors were segmented from dynamic contrast-enhanced MRI, followed by 3-dimensional extension of the margins with 10 mm. Amount of fibroglandular tissue (FGT) and enhancement features in these extended margins were automatically extracted from the MRI scans. Clinicohistopathological features were also obtained. Principal component analysis and multivariable logistic regression were used to develop a prediction model for E-DCIS. Discrimination and calibration were assessed, and bootstrapping was applied for internal validation. RESULTS: Extensive DCIS occurred in 48 (14.7%) of 326 tumors. Incomplete resection occurred in 56.3% of these E-DCIS-positive versus 9.0% of E-DCIS-negative tumors (P < 0.001). Five components with eigenvalue exceeding 1 were identified; 2 were significantly associated with E-DCIS. The first, positively associated, component expressed early and overall enhancement in the 10-mm tissue margin surrounding the MRI-visible tumor. The second, positively associated, component expressed human epidermal growth factor receptor 2 and amount of FGT around the MRI-visible tumor. The area under the curve value was 0.79 (0.76 after bootstrapping). CONCLUSIONS: Human epidermal growth factor receptor 2 status, early and overall enhancement in the 10-mm margin around the MRI-visible tumor, and amount of FGT in the 10 mm around the MRI-visible tumor were associated with E-DCIS

Moderate-to-deep sedation technique, using propofol and ketamine, allowing synchronised breathing for magnetic resonance high-intensity focused ultrasound (MR-HIFU) treatment for uterine fibroids : a pilot study

Background: Magnetic resonance high-intensity focused ultrasound (MR-HIFU) treatment for uterine fibroids is rapidly gaining popularity as a treatment modality. This procedure is generally uncomfortable, painful, and requires minimal or absence of movement and an MR-HIFU synchronised breathing pattern of the patient. Procedural sedation and analgesia protocols have become the standard practice in interventional radiology departments worldwide. The aim of this study was to explore if a sedation regimen with low-dose propofol and ketamine performed by trained non-medical sedation practitioners could result in relief of discomfort for the patient and in adequate working conditions for MR-HIFU treatment for uterine fibroids. Methods: In this study, conducted from August 2013 until November 2014, 20 patients were subjected to MR-HIFU treatment of uterine fibroids. Patients were deeply sedated using intravenous propofol and esketamine according to a standardised hospital protocol to allow synchronisation of the breathing pattern to the MR-HIFU. The quality of sedation for MR-HIFU and complications were recorded and analysed. The side effects of the sedation technique, the propofol and esketamine consumption rate, the duration of recovery, and patient satisfaction after 24 h were examined. Results: A total of 20 female patients (mean age 42.4 [range 32–53] years) were enrolled. Mean propofol/esketamine dose was 1309 mg/39.5 mg (range 692–1970 mg/ 23.6–87.9 mg). Mean procedure time was 269 min (range 140–295 min). Application of the sedation protocol resulted in a regular breathing pattern, which could be synchronised with the MRHIFU procedures without delay. The required treatment was completed in all cases. There were no major adverse events. Hypoxemia (oxygen desaturation Conclusions: The use of a specific combination of IV propofol and esketamine for procedural sedation and analgesia reduced the discomfort and pain during MR-guided HIFU treatments of uterine fibroids. The resulting regular breathing pattern allowed for easy synchronisation of the MR-HIFU procedure. Based on our results, esketamine and propofol sedation performed by trained non-medical sedation practitioners is feasible and safe, has a low risk of major adverse events, and has a short recovery time, avoiding a session of general anaesthesia

Patient Preferences for Minimally Invasive and Open Locoregional Treatment for Early-Stage Breast Cancer

Background: Noninvasive or minimally invasive treatments are being developed as alternatives to surgery for patients with early-stage breast cancer. Patients' preferences with regard to these new treatments have not been investigated. Objectives: To assess preferences of patients with breast cancer and of healthy women regarding these new techniques, compared with conventional surgical treatments. Methods: Six hypothetical breast cancer treatment-outcome scenarios were developed: three standard surgical scenarios (mastectomy, mastectomy with immediate implant-based reconstruction, and breast-conserving therapy [BCT]) and three minimally invasive or noninvasive scenarios (radiofrequency ablation, magnetic resonance-guided high-intensity focused ultrasound ablation, and single-dose ablative radiotherapy). Participants rated treatment-outcome scenarios by visual analogue scale (VAS) and time trade-off (TTO). The Friedman and post hoc Wilcoxon signed-rank tests were used to test whether scores were significantly different from BCT. Results: Seventy-one patients with breast cancer and 50 healthy volunteers participated. Overall, BCT was rated the highest in terms of VAS (0.80) and TTO (0.90) scores. After stratification, BCT ranked the highest in most subgroups, with the exception of healthy individuals, who had given the highest score to ablative boost (VAS, 0.80; TTO, 0.88). Mastectomy with immediate reconstruction was the least preferred in most subgroups. Conclusions: This study showed no significant preference for minimally invasive treatment for breast cancer. Using hypothetical scenarios, breast cancer survivors attributed the highest scores to BCT, whereas healthy volunteers showed a slight preference for minimally invasive treatments