M. A. A. J. van den Bosch

Image-guided focused ultrasound ablation of breast cancer: current status, challenges, and future directions

Image-guided focussed ultrasound (FUS) ablation is a non-invasive procedure that has been used for treatment of benign or malignant breast tumours. Image-guidance during ablation is achieved either by using real-time ultrasound (US) or magnetic resonance imaging (MRI). The past decade phase I studies have proven MRI-guided and US-guided FUS ablation of breast cancer to be technically feasible and safe. We provide an overview of studies assessing the efficacy of FUS for breast tumour ablation as measured by percentages of complete tumour necrosis. Successful ablation ranged from 20% to 100%, depending on FUS system type, imaging technique, ablation protocol, and patient selection. Specific issues related to FUS ablation of breast cancer, such as increased treatment time for larger tumours, size of ablation margins, methods used for margin assessment and residual tumour detection after FUS ablation, and impact of FUS ablation on sentinel node procedure are presented. Finally, potential future applications of FUS for breast cancer treatment such as FUS-induced anti-tumour immune response, FUS-mediated gene transfer, and enhanced drug delivery are discussed. Currently, breast-conserving surgery remains the gold standard for breast cancer treatment.

Ultrasound-guided laser-induced thermal therapy for small palpable invasive breast carcinomas: a feasibility study.

BackgroundThe next step in breast-conserving surgery for small breast carcinomas could be local ablation. In this study, the feasibility of ultrasound-guided laser-induced thermal therapy (LITT) is evaluated.MethodsPatients with large-core needle biopsy-proven invasive, palpable breast carcinoma (clinically ≤2xa0cm) underwent ultrasound-guided LITT, followed by surgical excision. Completeness of ablation was determined by both hematoxylin and eosin staining and nicotinamide adenosine diaphorase staining.ResultsFourteen patients completed the treatment. The mean histological tumor size was 17xa0mm (range, 8–37xa0mm); 6 of 14 tumors were histologically larger than the clinical entry threshold of 2xa0cm. The power applied in all patients was 7xa0W, and the mean treatment time was 21.4 min (range, 15–30 min). In one patient, a skin burn occurred, and one patient had a localized pneumothorax that could be treated conservatively. In 7 (50%) of 14 patients, the tumor was completely ablated, as confirmed by nicotinamide adenosine diaphorase staining. In 11 cases, extensive in-situ carcinoma was present. In one case, the in-situ carcinoma was also completely ablated. A total of seven (88%) of eight tumors <2xa0cm in size were completely ablated versus one (17%) of six tumors that were ≥2xa0cm in size (P = .026).ConclusionsSuccessful LITT of invasive breast cancer seems to be feasible when confined to small (<2xa0cm) nonlobular carcinomas without surrounding extensive in-situ component and angioinvasion. However, to implement LITT in a curative setting, improvements in imaging to more reliably preoperatively assess tumor size and monitoring of fiber tip placement and treatment affect are essential.

Efficacy of ‘radioguided occult lesion localisation’ (ROLL) versus ‘wire-guided localisation’ (WGL) in breast conserving surgery for non-palpable breast cancer: a randomised controlled multicentre trial

For the management of non-palpable breast cancer, accurate pre-operative localisation is essential to achieve complete resection with optimal cosmetic results. Radioguided occult lesions localisation (ROLL) uses the radiotracer, injected intra-tumourally for sentinel lymph node identification to guide surgical excision of the primary tumour. In a multicentre randomised controlled trial, we determined if ROLL is superior to the standard of care (i.e. wire-guided localisation, WGL) for preoperative tumour localisation. Women (>18 years.) with histologically proven non-palpable breast cancer and eligible for breast conserving treatment with sentinel node procedure were randomised to ROLL or WGL. Patients allocated to ROLL received an intra-tumoural dose of 120 Mbq technetium-99xa0m nanocolloid. The tumour was surgically removed, guided by gamma probe detection. In the WGL group, ultrasound- or mammography-guided insertion of a hooked wire provided surgical guidance for excision of the primary tumour. Primary outcome measures were the proportion of complete tumour excisions (i.e. with negative margins), the proportion of patients requiring re-excision and the volume of tissue removed. Data were analysed according to intention-to-treat principle. This study is registered at ClinincalTrials.gov, number NCT00539474. In total, 314 patients with 316 invasive breast cancers were enrolled. Complete tumour removal with negative margins was achieved in 140/162 (86xa0%) patients in the ROLL group versus 134/152 (88xa0%) patients in the WGL group (Pxa0=xa00.644). Re-excision was required in 19/162 (12xa0%) patients in the ROLL group versus 15/152 (10xa0%) (Pxa0=xa00.587) in the WGL group. Specimen volumes in the ROLL arm were significantly larger than those in the WGL arm (71 vs. 64xa0cm3, Pxa0=xa00.017). No significant differences were seen in the duration and difficulty of the radiological and surgical procedures, the success rate of the sentinel node procedure, and cosmetic outcomes. In this first multicentre randomised controlled comparison of ROLL versus WGL in patients with histologically proven breast cancer, ROLL is comparable to WGL in terms of complete tumour excision and re-excision rates. ROLL, however, leads to excision of larger tissue volumes. Therefore, ROLL cannot replace WGL as the standard of care.

Radioactive seed localization for non‐palpable breast cancer

Radioactive seed localization (RSL) is an alternative to wire localization for guiding surgical excision of non‐palpable breast cancer. This review provides an overview of the available evidence on the accuracy of RSL in patients undergoing breast‐conserving surgery.

MR liver imaging with Gd-EOB-DTPA: a delay time of 10 minutes is sufficient for lesion characterisation.

AbstractObjectivesTo assess whether, in patients with normal liver function, a hepatobiliary delay time of 10xa0min after Gd-EOB-DTPA injection is sufficient for lesion characterisation.MethodsIn 42 consecutive patients with suspected focal liver lesions, dynamic MRI was performed after intravenous Gd-EOB-DTPA, followed by hepatobiliary phases at 5, 10 and 20xa0min. The following items were assessed at each hepatobiliary phase: parenchymal enhancement, contrast agent excretion in bile ducts, lesion enhancement characteristics (hypo-, iso-, or hyperintensity, rim enhancement, central non-enhancement), and contrast- and signal-to-noise ratios, separately for hypo- and hyperintense lesions.ResultsFollowing enhancement, parenchymal signal intensity increased significantly up to 10xa0min (86.3%, Pu2009<u20090.001), and subsequently stabilised (86.5% after 20xa0min, Pu2009=u20090.223). Biliary contrast agent excretion was first observed in 2, 32 and 5 patients after 5, 10 and 20xa0min respectively. Hepatobiliary lesion enhancement characteristics observed after 5xa0min persisted during later hepatobiliary phases. CNR and SNR ratios increased significantly (Pu2009<u20090.05) up to 10xa0min after enhancement without further increase at 20xa0min, in hypo- and hyperintense lesions.ConclusionsIf lesion characterisation is the primary reason for performing MRI, a hepatobiliary delay time of 10xa0min after Gd-EOB-DTPA injection is sufficient in patients with normal liver function.Key Points• Magnetic resonance imaging is now a first line of investigation of the liver.n • Optimal CNR and SNR are achieved 10xa0min after Gd-EOB-DTPA injection.n • Typical enhancement characteristics are observed early and do not change.n • Ten-minute hepatobiliary delay is sufficient for characterisation of focal liver lesions.

MRI-guided needle localization of suspicious breast lesions: results of a freehand technique

Magnetic resonance imaging (MRI) can detect clinically and mammographically occult breast lesions. In this study we report the results of MRI-guided needle localization of suspicious breast lesions by using a freehand technique. Preoperative MRI-guided single-needle localization was performed in 220 patients with 304 MRI-only breast lesions at our hospital between January 1997 and July 2004. Procedures were performed in an open 0.5-T Signa-SP imager allowing real-time monitoring, with patient in prone position, by using a dedicated breast coil. MRI-compatible hookwires were placed in a noncompressed breast by using a freehand technique. MRI findings were correlated with pathology and follow-up. MRI-guided needle localization was performed for a single lesion in 150 patients, for two lesions in 56 patients, and for three lesions in 14 patients. Histopathologic analysis of these 304 lesions showed 104 (34%) malignant lesions, 51 (17%) high-risk lesions, and 149 (49%) benign lesions. The overall lesion size ranged from 2.0–65.0xa0mm (mean 11.2xa0mm). No direct complications occurred. Follow-up MRI in 54 patients showed that two (3.7%) lesions were missed by surgical biopsy. MRI-guided freehand needle localization is accurate and allows localization of lesions anterior in the breast, the axillary region, and near the chest wall.

MR imaging findings in two patients with hepatic veno-occlusive disease following bone marrow transplantation

Abstract. The aim of this study was to describe the MRI features of veno-occlusive disease (VOD) following bone-marrow transplantation in two patients. The MRI features consisted of hepatomegaly, hepatic vein narrowing, periportal cuffing, gallbladder wall thickening, marked hyperintensity of the gallbladder wall on T2-weighted images, ascites, and pleural effusion. In one patient, signs of reduced portal venous flow velocity were also observed. It is concluded that the use of MRI as a complementary technique following non-conclusive US examination enabled a timely diagnosis of this life-threatening disease in both patients.

Cost-Effectiveness of Radioguided Occult Lesion Localization (ROLL) Versus Wire-Guided Localization (WGL) in Breast Conserving Surgery for Nonpalpable Breast Cancer: Results from a Randomized Controlled Multicenter Trial

BackgroundAccurate preoperative localization of nonpalpable breast cancer is essential to achieve complete resection. Radioguided occult lesion localization (ROLL) has been introduced as an alternative for wire-guided localization (WGL). Although efficacy of ROLL has been established in a randomized controlled trial, cost-effectiveness of ROLL compared with WGL is not yet known. The objective of this study was to determine whether ROLL has acceptable cost-effectiveness compared with WGL.MethodsAn economic evaluation was performed along with a randomized controlled trial (ClinicalTrials.gov, No. NCT00539474). Women (>18xa0years) with histologically proven nonpalpable breast cancer and eligible for breast conserving treatment with sentinel node procedure were randomized to ROLL (nxa0=xa0162) or WGL (nxa0=xa0152). Empirical data on direct medical costs were collected, and changes in quality of life were measured over a 6-month period. Bootstrapping was used to assess uncertainty in cost-effectiveness estimates, and sensitivity of the results to the missing data approach was investigated.ResultsIn total, 314 patients with 316 invasive breast cancers were enrolled. On average ROLL required the same time as WGL for the surgical procedure (119 vs 118xa0min), resulted in a 7xa0% higher reinterventions risk, and 13xa0% more complications. Quality of life effects were similar (difference 0.00 QALYs 95xa0% CI (−0.04–0.05). Total costs were also similar for ROLL and WGL (+€26 per patient 95xa0% CI €−250–311).ConclusionROLL is comparable to WGL with respect to both costs and quality of life effects as measured with the EQ5D and will therefore not lead to more cost-effective medical care.

Accuracy of Multislice Liver CT and MRI for Preoperative Assessment of Colorectal Liver Metastases after Neoadjuvant Chemotherapy

Introduction: To determine the best imaging modality for preoperative detection, characterization and measurement of colorectal liver metastases (CRLM) after neoadjuvant chemotherapy (NAC). Methods: A total of 79 lesions in 15 patients with CRLM were included. Following NAC, all patients received multislice liver CT (MSCT) and magnetic resonance imaging (MRI) that were scored by two observers for lesion number, type, diameter (mm) and segmental location. Intraoperative findings, histopathology and follow-up imaging were used as reference standard for surgically treated patients; non-surgical candidates underwent follow-up imaging. Results: Lesion detection rate was similar for MSCT and MRI (76 and 80%, respectively, p = 0.648). Lesion characterization was significantly superior (p = 0.021) at MRI (89%, ĸ 0.747, p = 0.001) compared to MSCT (77%, ĸ 0.235, p = 0.005). Interobserver variability for diameter measurement was not significant at MRI (p = 0.909 [95% CI –1.245 to 1.395]), but significant at MSCT (p = 0.028 [95% CI –3.349 to –2.007]). Differences in diameter measurement were independent of observer (p = 0.131), and no statistical effect from imaging modality on diameter measurement was observed (p = 0.095). Conclusion: MRI is superior to MSCT in preoperative characterization and measurement of CRLM after NAC. Lesion detection rates for both modalities are comparable.

Folate, homocysteine levels, methylenetetrahydrofolate reductase (MTHFR) 677C T variant, and the risk of myocardial infarction in young women: effect of female hormones on homocysteine levels

Summary.u2002 In young women data are limited about the association between myocardial infarction (MI) and hyperhomocysteinemia, low folate or methylenetetrahydrofolate reductase (MTHFR) genotypes. The effect of oral contraceptive (OC) use on plasma homocysteine levels is not clear. We assessed the association between hyperhomocysteinemia, low folate, MTHFR 677TT mutation and risk of MI, and we investigated the effect of OC use on homocysteine levels in controls. In 181 patients with a first MI and 601 controls 18–49u2003years of age from a population‐based case–control study, non‐fasting blood samples were available. The homozygote mutant allele (TT) was detected in 12% of the patients and in 10% of controls. The odds ratio (OR) for MI in TT patients compared with the wild‐type (CC) controls was 1.3 [95% confidence interval (CI) 0.8, 2.3]. For all MTHFR genotypes combined, the OR for MI in the lowest quartile of folate (<5.4u2003nmolu2003L−1) compared with the highest quartile (>10.4u2003nmolu2003L−1) was 3.0 (95% CI 1.7, 5.1). A 2‐fold increased risk of MI was found in women with the TT genotype who had folate levels below the median of 7.4u2003nmolu2003L−1 compared with CC genotype and folate levels above the median (OR =u200a2.0; 95% CI 1.0, 3.7). Mean homocysteine levels were 12.2u2003µmolu2003L−1 in OC users and 12.3u2003µmolu2003L−1 in non‐users. Only at the 97.5 percentile (cut‐off 21.0u2003µmolu2003L−1) was the adjusted OR for higher vs. lower homocysteine levels increased by 2.8‐fold (95% CI 1.2, 6.8). Low folate is a risk factor for MI, particularly in women with the MTHFR 677TT genotype. Homocysteine levels were not influenced by OC use.