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Background: With the increasing number of non palpable breast carcinomas, the need of a good and reliable localization method increases. Currently the wire guided localization (WGL) is the standard of care in most countries. Radio guided occult lesion localization (ROLL) is a new technique that may improve the oncological outcome, cost effectiveness, patient comfort and cosmetic outcome. However, the studies published hitherto are of poor quality providing less than convincing evidence to change the current standard of care. The aim of this study is to compare the ROLL technique with the standard of care (WGL) regarding the percentage of tumour free margins, cost effectiveness, patient comfort and cosmetic outcome.Methods/design: The ROLL trial is a multi center randomized clinical trial. Over a period of 2-3 years 316 patients will be randomized between the ROLL and the WGL technique. With this number, the expected 15% difference in tumour free margins can be detected with a power of 80%. Other endpoints include cosmetic outcome, cost effectiveness, patient (dis)comfort, degree of difficulty of the procedures and the success rate of the sentinel node procedure. The rationale, study design and planned analyses are described.Trial Registration: (http://www.clinicaltrials.gov, study protocol number NCT00539474). [ABSTRACT FROM AUTHOR]

BACKGROUND: This population-based study describes the implementation of the sentinel node biopsy (SNB) in breast cancer patients in the Netherlands. We examined the extent of use over time of SNB in women who were considered eligible for SNB on the basis of their clinical status. METHODS: The study included a total of 35,465 breast cancer patients who were diagnosed with T1-2 tumours (5.0 cm), negative axillary lymph node status and no distant metastases upon clinical examination between 1st January 1998 and 31st December 2003 in six Comprehensive Cancer Centre regions in the Netherlands. Information on axillary surgery was classified as SNB alone, SNB+axillary lymph node dissection (ALND), ALND alone or none. Patterns of use of axillary surgery were summarised as the proportion of patients receiving each surgery type. RESULTS: Overall, 25.7% of patients underwent SNB alone, 19.1% underwent SNB+ALND, 50.0% had ALND alone and 5.2% did not have axillary surgery. SNB was more common in women who had breast-conserving surgery: 50.5% of patients who received breast-conserving surgery underwent SNB compared to 40.7% of patients who had mastectomy (p<0.0001). Amongst patients receiving breast-conserving treatment, 31.7% had SNB as final axillary surgery, whilst 20.5% of patients who had mastectomy had SNB alone (p<0.0001). The proportion of women who underwent a SNB alone or in combination with ALND increased over the period 1998-2003, from 2.1% to 45.8% and from 6.7% to 24.8%, respectively. There were marked differences in the patterns of dissemination of the use of SNB between regions: by 2003, the difference between the regions with the highest and lowest proportion of use was 25%. CONCLUSIONS: SNB has become the standard-of-care for the treatment of breast cancer patients clinically diagnosed with T1-2 tumours, clinically negative lymph nodes and without distant metastases. In 2003, 70.6% of patients with early breast cancer in the Netherlands received SNB, and within this group, 64.9% of patients had SNB as the final axillary treatment. Implementation of SNB may depend on factors associated with regional organisation of care. [ABSTRACT FROM AUTHOR]

To localize ectopic gastric mucosa in patients with unexplained gastrointestinal bleeding and diagnose a Meckel diverticulum, 99m Tc-pertechnetate imaging is the standard procedure. H2 inhibitor pretreatment enhances the sensitivity of the scan by reducing washout of 99m Tc activity from the intestinal lumen. We aim to provide evidence of the effectiveness of the proton pump inhibitor esomeprazole as an ideal substitute for ranitidine. Methods: The scan quality for 142 patients who underwent a Meckel scan during a period of 10 y was evaluated. The patients were pretreated with ranitidine orally or intravenously before a switch to a proton pump inhibitor after ranitidine was no longer available. Good scan quality was characterized by the absence of 99m Tc-pertechnetate activity in the gastrointestinal lumen. The effectiveness of esomeprazole to diminish 99m Tc-pertechnetate release was compared with the standard treatment using ranitidine. Results: Pretreatment with intravenous esomeprazole resulted in 48% of scans with no 99m Tc-pertechnetate release, 17% with release either in the intestine or in the duodenum, and 35% with 99m Tc-pertechnetate activity both in the intestine and in the duodenum. Evaluation of scans obtained after oral ranitidine and intravenous ranitidine showed absence of activity in both intestine and duodenum in 16% and 23% of the cases, respectively. The indicated time to administer esomeprazole before starting the scan procedure was 30 min, but a delay of 15 min did not negatively influence the scan quality. Conclusion: This study confirms that esomeprazole, 40 mg, when administered intravenously 30 min before a Meckel scan, enhances the scan quality comparably to ranitidine. This procedure can be incorporated into protocols., (© 2023 by the Society of Nuclear Medicine and Molecular Imaging.)

Background: A shift towards less burdening and more patient friendly treatments for breast cancer is currently ongoing. In low-risk patients with early-stage disease, accelerated partial breast irradiation (APBI) is an alternative for whole breast irradiation following breast-conserving surgery. MRI-guided single dose ablative APBI has the potential to offer a minimally burdening, non-invasive treatment that could replace current breast-conserving therapy., Methods: The ABLATIVE study is a prospective, single arm, multicenter study evaluating preoperative, single dose, ablative radiation treatment in patients with early-stage breast cancer. Patients with core biopsy proven non-lobular invasive breast cancer, (estrogen receptor positive, Her2 negative, maximum tumor size 3.0 cm on diagnostic MRI) and a negative sentinel node biopsy are eligible. Radiotherapy (RT) planning will be performed using a contrast enhanced (CE) planning CT-scan, co-registered with a CE-MRI, both in supine RT position. A total of twenty-five consecutive patients will be treated with a single ablative RT dose of 20 Gy to the tumor and 15 Gy to the tumorbed. Follow-up MRIs are scheduled within 1 week, 2, 4 and 6 months after single-dose RT. Breast-conserving surgery is scheduled at six months following RT. Primary study endpoint is pathological complete response. Secondary study endpoints are the radiological response and toxicity. Furthermore, patients will fill out questionnaires on quality of life and functional status. Cosmetic outcome will be evaluated by the treating radiation oncologist, patient and 'Breast Cancer Conservation Treatment cosmetic results' software. Recurrence and survival rates will be assessed. The patients will be followed up to 10 years after diagnosis. If patients give additional informed consent, a biopsy and a part of the irradiated specimen will be stored at the local Biobank and used for future research on radiotherapy response associated genotyping., Discussion: The ABLATIVE study evaluates MRI-guided single dose ablative RT in patients with early-stage breast cancer, aiming at a less burdening and non-invasive alternative for current breast-conserving treatment., Trial Registration: ClinicalTrials.gov registration number NCT02316561 . The trial was registrated prospectively on October 10th 2014.

Background: The role of 2-[ 18 F]-fluoro-2-deoxy-D-glucose (FDG)-positron emission tomography (PET)/computed tomography (CT) in routine diagnostic staging remains controversial. In case of discordance between FDG-PET and CT, a compromise has to be made between the risk of false positive FDG-PET and the risk of delaying appropriate salvage intervention. Second, with intensity modulated radiation therapy (IMRT), smaller radiation fields allow tissue sparing, but could also lead to more marginal failures., Methods: We retrospectively studied 283 patients with head and neck carcinoma scheduled for radiotherapy between 2002 and 2010. We analyzed the influence of FDG-PET/CT versus CT alone on defining nodal target volume definition and evaluated its long-term clinical results. Second, the location of nodal recurrences was related to the radiation regional dose distribution., Results: In 92 patients, CT and FDG-PET, performed in mold, showed discordant results. In 33%, nodal staging was altered by FDG-PET. In 24%, FDG-PET also led to an alteration in nodal treatment, including a nodal upstage of 18% and downstage of 6%. In eight of these 92 patients, a regional recurrence occurred. Only two patients had a recurrence in the discordant node on FDG-PET and CT and both received a boost (high dose radiation)., Conclusion: These results support the complementary value of FDG-PET/CT compared to CT alone in defining nodal target volume definition for radiotherapy of head and neck cancer.

Background: Omitting extensive lymph node dissection could reduce esophagectomy morbidity in patients without lymph node metastases. Sentinel node biopsy may identify abdominal or thoracic lymph node metastases, thereby differentiating treatment. Feasibility of this approach was investigated in Western European esophageal cancer patients with advanced disease, without lymph node metastases at diagnostic work-up., Methods: The sentinel node biopsy was performed in eight esophageal cancer patients with cT1-3N0 disease. One day pre-operatively, Tc-99m-labeled nanocolloid was endoscopically injected around the tumor. Lymphoscintigraphy was performed 1 and 3 h after injection. All patients underwent robotic thoracolaparoscopic esophagectomy with two-field lymph node dissection. Intraoperatively, sentinel nodes were detected by gamma probe. The resection specimen was analyzed for remaining activity by scintigraphy and gamma probe., Results: Visualization rates of lymphoscintigraphy 1 and 3 h after tracer injection were 88 and 100%, respectively. Intraoperative identification rate was 38%. Postoperative identification was possible in all patients using the gamma probe to analyze the resection specimen. In 5/8 patients, lymph node metastases were found at histopathology, none of which was detected by the sentinel node biopsy. No adverse events related to the sentinel node biopsy were observed., Conclusions: In our advanced esophageal cancer patients who underwent thoracolaparoscopic esophagectomy, the sentinel node biopsy did not predict lymph node status. Probably the real sentinel node could not be identified due to localization adjacent to the primary tumor or bypassing due to metastatic tumor involvement. Therefore, we consider the sentinel node biopsy not feasible in advanced esophageal cancer.

Unlabelled: We aimed to explore the accuracy of (99m)Tc SPECT/MRI fusion for the selective assessment of nonenlarged sentinel lymph nodes (SLNs) for diagnosing metastases in early-stage cervical cancer patients., Methods: We consecutively included stage IA1-IIB1 cervical cancer patients who presented to our tertiary referral center between March 2011 and February 2015. Patients with enlarged lymph nodes (short axis ≥ 10 mm) on MRI were excluded. Patients underwent an SLN procedure with preoperative (99m)Tc-nanocolloid SPECT/CT-based SLN mapping. When fused datasets of the SPECT and MR images were created, SLNs could be identified on the MR image with accurate correlation to the histologic result of each individual SLN. An experienced radiologist, masked to histology, retrospectively reviewed all fused SPECT/MR images and scored morphologic SLN parameters on a standardized case report form. Logistic regression and receiver-operating curves were used to model the parameters against the SLN status., Results: In 75 cases, 136 SLNs were eligible for analysis, of which 13 (9.6%) contained metastases (8 cases). Three parameters-short-axis diameter, long-axis diameter, and absence of sharp demarcation-significantly predicted metastatic invasion of nonenlarged SLNs, with quality-adjusted odds ratios of 1.42 (95% confidence interval [CI], 1.01-1.99), 1.28 (95% CI, 1.03-1.57), and 7.55 (95% CI, 1.09-52.28), respectively. The area under the curve of the receiver-operating curves combining these parameters was 0.749 (95% CI, 0.569-0.930). Heterogeneous gadolinium enhancement, cortical thickness, round shape, or SLN size, compared with the nearest non-SLN, showed no association with metastases (P= 0.055-0.795)., Conclusion: In cervical cancer patients without enlarged lymph nodes, selective evaluation of only the SLNs-for size and absence of sharp demarcation-can be used to noninvasively assess the presence of metastases., (© 2016 by the Society of Nuclear Medicine and Molecular Imaging, Inc.)

Background: Accurate evaluation of the spleen is an important component of staging lymphoma, because this may have prognostic and therapeutic implications., Purpose: To determine the diagnostic value of whole-body magnetic resonance imaging (MRI), including diffusion-weighted imaging (whole-body MRI-DWI) in the detection of splenic involvement in lymphoma., Material and Methods: This IRB approved, prospective multicenter study included a total of 107 patients with newly diagnosed, histologically proven lymphoma who underwent 1.5 T whole-body MRI-DWI and FDG-PET/CT. Whole-body MRI-DWI and FDG-PET/CT were independently evaluated by a radiologist and a nuclear medicine physician, in a blinded manner. Splenic involvement at MRI was defined as splenic index > 725 cm(3) or discrete nodules. At FDG-PET/CT splenic involvement was defined as splenic uptake greater than liver uptake or hypodense nodules at contrast-enhanced CT. FDG-PET/CT augmented with follow-up imaging after treatment was used as reference standard., Results: Splenic involvement was detected with FDG-PET/CT in 21 patients, all demonstrating response to treatment. The sensitivity, specificity, positive predictive value, and negative predictive value of whole-body MRI-DWI for the detection of splenic involvement were 85.7 %, 96.5 %, 85.7%, and 96.5%, respectively. Three out of six discrepancies were related to suboptimal criterion of splenic size used with whole-body MRI-DWI versus the size-independent FDG uptake., Conclusion: Whole-body MRI-DWI is reasonably accurate in the detection of splenic lymphomatous involvement., (© The Foundation Acta Radiologica 2015.)

Purpose: The purpose of this study is to evaluate the efficacy of (18)F-FDG-PET as first-line diagnostic investigation, prior to performing a direct laryngoscopy with biopsy under general anesthesia, in patients suspected of recurrent laryngeal carcinoma after radiotherapy., Patients and Methods: 150 patients suspected of recurrent T2-4 laryngeal carcinoma at least two months after prior (chemo)radiotherapy with curative intent for resectable disease were randomized to direct laryngoscopy (CWU: conventional workup strategy) or to (18)F-FDG-PET only followed by direct laryngoscopy if PET was assessed 'positive' or 'equivocal' (PWU: PET based workup strategy), to compare the effectiveness of these strategies. Primary endpoint was the number of indications for direct laryngoscopies classified as unnecessary based on absence of recurrence, both on direct laryngoscopy and on six month follow up. Safety endpoints comprised resectability of recurrent lesions and completeness of surgical margins following salvage laryngectomy., Results: Intention-to-treat analyses were performed on all randomized patients (CWU: n=74, PWU: n=76). Tumor recurrence was similar in both groups: 45 patients (30%; 21 CWU, 24 PWU) within six months. In 53 patients in the CWU arm (72%, 95% CI: 60-81) unnecessary direct laryngoscopies were performed compared to 22 in the PWU arm (29%, 95% CI: 19-40) (p<0·0001). The percentage of salvage laryngectomies (resectability) and positive surgical margins were similar between CWU and PWU (81%, 63% respectively, p=0·17, and 29%, 7%, respectively, p=0.20). The prevalence of the combination of local unresectability and positive margins is in the CWU group 24% and in the PWU group 8%. No difference (p=0.32) in disease specific survival between both groups was found., Conclusion: In patients with suspected laryngeal carcinoma after radiotherapy, PET as the first diagnostic procedure can reduce the need for direct laryngoscopy by more than 50% without jeopardizing quality of treatment., (Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.)

Aims: To study additional benefits of performing Tc-99m dimercaptosuccinic acid (Tc-99m-DMSA) scintigraphy as part of the follow-up of adults with spinal dysraphism (SD), compared with ultrasonography, with regard to finding renal scarring and difference in split renal function., Methods: Between January 2011 and April 2013 every patient visiting our specialized outpatient clinic for adults with SD was invited to undergo both renal ultrasonography and Tc-99m-DMSA scintigraphy. Outcomes of both modalities were compared, with focus on renal scarring. The relation between renal scarring and hypertension was also assessed., Results: In total, 122 patients (with 242 renal units) underwent both renal scintigraphy and ultrasonography. More scars were seen on DMSA scintigraphy than on ultrasonography: 45.9% vs. 10.3% of renal units; P < 0.001. Renal scarring seen on DMSA was associated with the presence of hypertension (P = 0.049) whereas scarring seen on ultrasonography was not (P = 0.10). If ultrasonography was difficult to interpret, many more scars were missed on ultrasonography (78.9%) compared with easily interpretable ultrasonographic images (30.6%; P < 0.001)., Conclusions: In adults with SD, ultrasonography is of value to diagnose dilatation and stones of the upper urinary tract; however, compared with DMSA renography, renal scars are often missed, especially when the ultrasound is difficult to interpret., (© 2014 Wiley Periodicals, Inc.)

Unlabelled: We aimed to compare SPECT/CT and lymphoscintigraphy on overall and bilateral sentinel lymph node (SLN) detection in cervical cancer patients., Methods: A systematic search was performed on August 1, 2014, in PubMed, Embase, Scopus, and the Cochrane library. The syntax was based on synonyms of the terms cervical cancer, SPECT/CT, and lymphoscintigraphy. Retrieved articles were screened on their title/abstract and considered eligible when an SLN procedure was performed using both imaging modalities and if detection results were reported. Two independent reviewers assessed all included studies on methodologic quality using QUADAS-2. Studies were pooled on their odds ratios (ORs) with a random-effects model., Results: The search yielded 962 unique articles, of which 8 were ultimately included. The studies were recent retrospective or prospective cohort studies of limited size (n = 7-51) but sufficient methodologic quality. The median overall detection (≥1 SLN in a patient) was 98.6% for SPECT/CT (range, 92.2%-100.0%) and 85.3% for lymphoscintigraphy (range, 70.0%-100.0%). This corresponded to a pooled overall SLN detection OR of 2.5 (95% CI, 1.2-5.3) in favor of SPECT/CT. The reported median bilateral detection (≥1 SLN in each hemipelvis) was 69.0% for SPECT/CT (range, 62.7%-79.3%) and 66.7% for lymphoscintigraphy (range, 56.9%-75.8%), yielding a pooled OR of 1.2 (95% CI, 0.7-2.1). No significant difference in the number of visualized SLNs was observed at a pooled ratio of 1.2 (95% CI, 0.9-1.6)., Conclusion: In cervical cancer patients, preoperative SLN imaging with SPECT/CT results in superior overall SLN detection in comparison with planar lymphoscintigraphy., (© 2015 by the Society of Nuclear Medicine and Molecular Imaging, Inc.)

Introduction: Our aim was to evaluate the development of microbubble-enhanced sentinel lymph node (SLN) localization with placement of an I-125 seed in breast cancer patients as a potential alternative for SLN localization with nanocolloid. The study is conducted and reported following the IDEAL recommendations for evaluation of a new technique at Stage 2a (Prospective Development Study)., Methods: Fourteen consecutive patients with 15 lesions underwent microbubble-enhanced SLN localization with placement of an I-125 seed after the standard SLN localization (nanocolloid). We placed an I-125 seed within or near the SLN following its identification using intradermally injected microbubbles. The SLN was excised guided by nanocolloid and the SLN containing the I-125 seed was searched for. All technical modifications are described and standardized outcomes measured., Results: Twelve (80%) microbubble procedures with I-125 seed placements were technically successful. In three cases no microbubble-enhancing lymph node could be detected. Intraoperatively, we found nine I-125 seeds within 0.5 cm of the nanocolloid confirmed SLN. One I-125 seed was found next to a non-SLN and two I-125 seeds were not near any lymph node. Overall, the procedure was successful in 60% (9 out of 15) of the cases., Conclusion: Given the low success rate, we conclude that microbubble-enhanced SLN is not a viable alternative to the standard SLN procedure. Modifications to this technique did not improve its performance. Planned study (NTR3690 http://www.trialregister.nl/trialreg/admin/rctview.asp?TC=3690) was stopped early due to this conclusion and results reported in order to provide a full and transparent record of the evolution of technique., (Copyright © 2015 Surgical Associates Ltd. Published by Elsevier Ltd. All rights reserved.)

Background: The aim of this study was to investigate the corrosive behaviour of stainless steel archwires in a more clinically relevant way by bending and exposing to various pH., Methods: One hundred and twenty pieces of rectangular stainless steel wires (0.43 × 0.64 mm) were randomly assigned into four groups. In each group, there were 15 pieces of bent wires and 15 straight ones. Prior to measurements of the wires, as individual experimental groups (group 1, 2, and 3), the wires were exposed to artificial saliva for 4 weeks at pH 5.6, 6.6, and 7.6, respectively. A control group of wires (group 4) remained in air for the same period of time before sent for measurements. Surface roughness (Ra-value) was measured by a profilometer. Young's modulus and maximum force were determined by a four-point flexural test apparatus. Scanning electron microscopy was used to observe the surface morphology of straight wire. Differences between groups were examined using a two-way analysis of variance (ANOVA)., Results: Mean surface roughness values, flexural Young's moduli, and maximum force values of bent wires are significantly different from those of the straight wires, which was the main effect of wire bending, ignoring the influence of pH. A significant effect was found between Ra-values regarding the main effect of pH, ignoring the influence of shape. There was a significant interaction effect of bending and pH on flexural Young's moduli of stainless steel archwires, while pH did not show much impact on the maximum force values of those stainless steel wires. Bigger surface irregularities were seen on SEM images of straight wires immersed in artificial saliva at pH 5.6 compared to artificial saliva at other pH values. Surface depth (Rz) was more sensitive than Ra in revealing surface roughness, both measured from 3D reconstructed SEM images. Ra showed a comparable result of surface roughness to Ra-value measured by the profilometer., Conclusions: Bending has a significant influence on surface roughness and mechanical properties of rectangular SS archwires. pH plays a synergistic effect on the change of mechanical properties of stainless steel (SS) wires along with wire bending.

Objective: To compare whole-body MRI, including diffusion-weighted imaging (whole-body MRI-DWI), with FDG-PET/CT for staging newly diagnosed paediatric lymphoma., Methods: A total of 36 children with newly diagnosed lymphoma prospectively underwent both whole-body MRI-DWI and FDG-PET/CT. Whole-body MRI-DWI was successfully performed in 33 patients (mean age 13.9 years). Whole-body MRI-DWI was independently evaluated by two blinded observers. After consensus reading, an unblinded expert panel evaluated the discrepant findings between whole-body MRI-DWI and FDG-PET/CT and used bone marrow biopsy, other imaging data and clinical information to derive an FDG-PET/CT-based reference standard., Results: Interobserver agreement of whole-body MRI-DWI was good [all nodal sites together (κ = 0.79); all extranodal sites together (κ = 0.69)]. There was very good agreement between the consensus whole-body MRI-DWI- and FDG-PET/CT-based reference standard for nodal (κ = 0.91) and extranodal (κ = 0.94) staging. The sensitivity and specificity of consensus whole-body MRI-DWI were 93 % and 98 % for nodal staging and 89 % and 100 % for extranodal staging, respectively. Following removal of MRI reader errors, the disease stage according to whole-body MRI-DWI agreed with the reference standard in 28 of 33 patients., Conclusions: Our results indicate that whole-body MRI-DWI is feasible for staging paediatric lymphoma and could potentially serve as a good radiation-free alternative to FDG-PET/CT., Keypoints: • Accurate staging is important for treatment planning and assessing prognosis • Whole-body MRI-DWI could be a good radiation-free alternative to FDG-PET/CT • Interobserver agreement of whole-body MRI-DWI is good • Agreement between whole-body MRI and the FDG-PET/CT reference standard is good • Most discrepancies were caused by suboptimal accuracy of size measurements on MRI.

Objective: To compare preoperative sentinel node (SN) mapping with planar lymphoscintigraphy (LSG) to single photon emission computed tomography with computed tomography (SPECT-CT) for differences in intraoperative SN retrieval time in surgically treated cervical cancer patients., Methods: In cervical cancer patients planned for radical surgery, one day preoperatively, 220-290 MBq technetium-99m-nanocolloid was injected intracervically in four quadrants. Subsequent SN mapping was performed by either LSG (09.2009-03.2011) or SPECT-CT (03.2011-10.2012). The SN resection, by four armed robot assisted laparoscopy, was based on blue dye and technetium-99m and followed by pelvic lymph node dissection. Timing of perioperative care, including SN procedure times, was prospectively registered., Results: Out of the 62 subjects included, 33 (53.2%) underwent LSG and 29 (46.8%) SPECT-CT. No significant differences in baseline characteristics were observed. Bi- and unilateral SN visualization rates were 75.8% and 15.2% for LSG versus 86.2% and 6.9% for SPECT-CT (p=0.299 and p=0.305, respectively). Intraoperative bi/unilateral SN detection occurred in 84.8% and 9.1% of LSG subjects versus 89.7% and 3.4% for SPECT-CT (p=0.573 and p=0.616). Correlation in SN location between mapping and surgery was low for LSG (Spearman ρ=0.098; p=0.449) but high for SPECT-CT (ρ=0.798; p<0.001). Bilateral intraoperative SN retrieval times for LSG and SPECT-CT were 75.4±33.5 and 50.1±15.6 min, resulting in an average difference of 25.4 min (p=0.003)., Conclusion: SPECT-CT significantly reduces intraoperative SN retrieval with a clinically relevant time compared to LSG. The trend towards better bilateral visualization rates and significantly higher anatomical concordance may partly explain the observed difference in SN retrieval time., (Copyright © 2013. Published by Elsevier Inc.)

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-99 m 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 (86 %) patients in the ROLL group versus 134/152 (88 %) patients in the WGL group (P = 0.644). Re-excision was required in 19/162 (12 %) patients in the ROLL group versus 15/152 (10 %) (P = 0.587) in the WGL group. Specimen volumes in the ROLL arm were significantly larger than those in the WGL arm (71 vs. 64 cm(3), P = 0.017). 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.

Introduction: Timing of image acquisition in breast cancer sentinel node scintigraphy remains a subject of debate. Therefore, the performance of our protocol in which images are acquired 1 and 2 h after injection was evaluated. The results of sentinel node scintigraphy 1 and 2 h after injection were compared with regard to the sentinel lymph nodes visualized., Methods: We studied 132 patients who were consecutively referred for sentinel lymph node biopsy. 99mTc-albumine nanocolloid (120 MBq) was injected peritumourally into patients with palpable tumours and intratumourally into patients with nonpalpable tumours. All scintigraphic images taken for the sentinel node procedure were evaluated. The number of sentinel nodes per anatomic localization and the interpretability of the images were scored., Results: A total of 132 patients underwent sentinel node scintigraphy 1 h after injection. Of these, 117 patients also underwent sentinel node scintigraphy 2 h after injection. An axillary sentinel node was visualized in 79.5 and 95.7% of patients, respectively, 1 and 2 h after injection. In 20.5% of the patients the images acquired 1 h after injection did not show a sentinel node. Furthermore, in all procedures, the images 1 h after injection were of no added value to those acquired 2 h after injection., Conclusion: Scintigraphic imaging 2 h after a single peritumoural or intratumoural administration of about 120 MBq 99mTc-albumine nanocolloid yields an axillary sentinel node in over 95% of cases. Imaging 1 h after injection is of no additional value and can be omitted.

Objective: Evaluation of the feasibility and safety of radiocolloid as a tracer for sentinel lymph node (SLN) mapping in colon cancer., Methods: A feasibility study was conducted in consecutive colon cancer patients who were surgically treated at our institute. During preoperative colonoscopy, radiocolloid was injected around the tumour, followed by scintigraphic imaging to identify SLNs. SLNs were identified intraoperatively by a gamma probe and postoperatively by additional ex-vivo scintigraphy of the resection specimen. All retrieved SLNs were examined by histopathological ultrastaging. Standard oncologic laparoscopic resections with lymphadenectomy were performed following the identification of SLNs in all patients., Results: Fourteen patients were included. At least one SLN was identified in 86% of patients. In one patient (7%) SLNs could be detected intraoperatively. In 83% of patients, the SLNs accurately reflected the tumour status of the remaining lymph nodes. Aberrant lymphatic drainage was preoperatively identified in one patient (7%), but this could not be confirmed intraoperatively. Sensitivity was 67% and the false-negative rate was 33%. Seventeen per cent of patients were upstaged because of SLN micrometastases., Conclusion: SLN mapping in colon cancer using radiocolloid as a single tracer is feasible and safe. However, it was difficult to identify SLNs intraoperatively because of high radioactivity at the injection site. Furthermore, the protocol is labour intensive, especially because of the additional colonoscopic tracer injection. Sensitivity is not better than when blue dye is used, and aberrant lymphatic drainage patterns are scarce. Therefore, this technique is not preferred for SLN mapping in colon cancer.

Routine removal of the internal mammary chain (IMC) sentinel node in breast cancer patients remains a subject of discussion. The aim of this study was to determine the impact of routinely performed IMC sentinel node biopsy on the systemic and locoregional treatments plan. All patients with biopsy proven breast cancer who underwent a sentinel node procedure between 2002 and 2011 were included in a prospective database. In cases of IMC drainage, successful exploration of the IMC (i.e., sentinel node removed) and surgical complications were registered. If the removed sentinel node contained malignant cells we determined if this altered the treatment plan when practising the current guidelines. In total, 119 of the 493 included patients showed IMC drainage on lymphoscintigraphy. Exploration of the IMC was performed in 107 (89 %) patients; in 86/107 (80 %) exploration was successful. In 14/107 patients (13 %) the IMC sentinel node was tumor positive. Macro and micro metastases were found in eight and six patients, respectively. In the group of patients who underwent surgical exploration of the IMC, systemic treatment was changed in none, radiotherapy treatment in 13/107 patients (11 %). Routine sentinel node biopsy of the IMC does not alter the systemic treatment. Radiotherapy treatment is altered in a small proportion of the patients; however, solid scientific evidence for this adjustment is lacking.

TLR (Toll-like receptor) activation-induced inflammatory responses are important in the progression of atherosclerosis. We previously showed that TLR-dependent leucocyte responsiveness is acutely attenuated following percutaneous coronary intervention or vascular surgery. Furthermore, cytokine release following whole-blood TLR-2 and TLR-4 stimulation is negatively correlated with fractional flow reserve, suggesting that chronic ischaemia can elicit an enhanced inflammatory response. In the present study, we assessed the association between leucocyte TLR-2 and TLR-4 responsiveness and pre-existent and inducible ischaemia in patients undergoing SPECT (single-photon emission computed tomography)-MPI (myocardial perfusion imaging). TLR-2, TLR-4 and CD11b expression on monocytes were measured in blood samples that were obtained from 100 patients with suspected coronary artery disease before and after myocardial stress testing for SPECT-MPI. IL-8 (interleukin-8) levels were determined after whole-blood stimulation with Pam3Cys (TLR-2) and LPS (lipopolysaccharide; TLR-4). On the basis of SPECT-MPI, patients were categorized into three groups: reversible defect, irreversible defect and no defect. Myocardial stress induced a reduction in TLR-4 expression (2.46±0.21 compared with 2.17±0.16 arbitrary units, P=0.001) and CD11b expression (83.2±1.73 compared with 76.0±1.89 arbitrary units, P<0.001). TLR-induced IL-8 production before myocardial stress induction was not associated with the results of SPECT-MPI. However, a significant decrease in IL-8 production following TLR stimulation was observed after stress, which was more pronounced in patients with a reversible defect. In conclusion, inducible ischaemia is associated with a decrease in whole-blood TLR-2 and TLR-4 response. These results point to a regulating role of TLRs in order to prevent excessive inflammatory events known to occur during acute ischaemia.

Cardiac sarcoidosis (CS) is a multisystem granulomatous disorder of unknown etiology with frequent cardiac involvement. We describe a patient presenting with a ventricular tachycardia, presumably originating in the right ventricle (RV). This patient had a malignant clinical course with initial diagnosis of arrhythmogenic right ventricular dysplasia/cardiomyopathy (ARVD/C); however, at postmortem histopathology revealed epithelioid granulomas with fibrosis localized in the interventricular septum, typical for sarcoidosis, without signs of extracardiac sarcoidosis. In conclusion, sarcoid myocarditis may present with signs and symptoms of ARVD/C and only histopathology can differentiate the 2 diseases. In the cases of atypical clinical presentation or when histopathological proof of ARVD is absent, a close follow-up is advisable to identify other potentially treatable disorders.

Iatrogenic displacement and mechanical transport of epithelial cells to the sentinel node (SN) has been suggested to result in false-positive findings in breast cancer patients, but little biologic evidence has yet been presented for this hypothesis. As malignant nuclei are larger than benign ones, nuclear morphometry of SN isolated tumor cells (ITC) could provide relevant information with regard to the malignant origin-or-not of epithelial cells in the SN. In patients with primary invasive breast cancer and SN ITC with (N=16) or without (N=45) non-SN involvement, nuclear morphometry was performed on the primary tumor as well as on the ITC in the SN. Nuclear size in the primary tumor was compared with that in the corresponding ITC. Patients with SN micrometastases (N=30) and SN macrometastases (N=30) served as controls. Nuclear size of ITC was significantly smaller compared with nuclear size of the corresponding primary tumor (P<0.0001). In contrast, there were no differences in nuclear size between SN micrometastases and macrometastases on the one hand and their corresponding primary tumors on the other. In addition, a subgroup of cases (10/61, 16%) with benign morphometric features of SN ITC nuclei (small and isomorph) could be discerned that had no non-SN metastases. In conclusion, nuclei of SN ITC are significantly smaller compared with the corresponding primary tumor and are often not associated with non-SN involvement. This supports the hypothesis that some of these deposits could represent benign epithelium or degenerated malignant cells lacking outgrowth potential.

Background: The majority of sentinel node (SN) positive breast cancer patients do not have additional non-SN involvement and may not benefit from axillary lymph node dissection (ALND). Previous studies in melanoma have suggested that microanatomic localization of SN metastases may predict non-SN involvement. The present study was designed to assess whether these criteria might also be used to be more restrictive in selecting breast cancer patients who would benefit from an ALND., Methods: A consecutive series of 357 patients with invasive breast cancer and a tumor-positive axillary SN, followed by an ALND, was reviewed. Microanatomic SN tumor features (subcapsular, combined subcapsular and parenchymal, parenchymal, extensive localization, multifocality, and the penetrative depth from the SN capsule) were evaluated for their predictive value for non-SN involvement., Results: Non-SN metastases were found in 136/357 cases (38%). Microanatomic location and penetrative depth of SN metastases were significant predictors for non-SN involvement (<0.001); limited penetrative depth was associated with a low frequency of non-SN involvement with a minimal of 10%., Conclusions: Microanatomic location and penetrative depth of breast cancer SN metastases predict non-SN involvement. However, based on these features no subgroup of patients could be selected with less than 10% non-SN involvement.

Primary and secondary liver cancer have longtime been characterized by an overall poor prognosis since the majority of patients are not candidates for surgical resection with curative intent, systemic chemotherapy alone has rarely resulted in long-term survival, and the role of conventional external beam radiation therapy has traditionally been limited due to the relative sensitivity of the liver parenchyma to radiation. Therefore, a host of new treatment options have been developed and clinically introduced, including radioembolization techniques, which are the main topic of this paper. In these locoregional treatments liver malignancies are passively targeted because, unlike the normal liver, the blood supply of intrahepatic tumors is almost uniquely derived from the hepatic artery. These internal radiation techniques consist of injecting either yttrium-90 ((90)Y) microspheres, or iodine-131 ((131)I) or rhenium-188 ((188)Re) labeled lipiodol into the hepatic artery. Radioactive lipiodol is used exclusively for treatment of primary liver cancer, whereas (90)Y microsphere therapy is applied for treatment of both primary and metastatic liver cancers. Favorable clinical results have been achieved, particularly when (90)Y microspheres were used in conjunction with systemic chemotherapy. The main advantages of radiolabeled lipiodol treatment are that it is relatively inexpensive (especially (188)Re-HDD-lipiodol) and that the administration procedure is somewhat less complex than that of the microspheres. Holmium-166 ((166)Ho) loaded poly(L-lactic acid) microspheres have also been developed and are about to be clinically introduced. Since (166)Ho is a combined beta-gamma emitter and highly paramagnetic as well, it allows for both (quantitative) scintigraphic and magnetic resonance imaging.

Ductal carcinoma in situ (DCIS) of the breast is defined as a proliferation of malignant epithelial cells within breast ducts without evidence of invasion through the basement membrane. The detection rate of DCIS of the breast has dramatically increased since the mid-1980s as the result of the widespread use of screening mammography. DCIS currently represents about 15-25% of all breast cancers detected in population screening programmes. Although inherently a non-invasive disease, occult invasion with the potential of lymph node metastases may occur. Where performing an axillary lymph node dissection-or-not for DCIS used to be an important dilemma, the same now holds for the sentinel node biopsy. This article reviews the potential role of the sentinel node biopsy (SNB) in patients with DCIS. We conclude that based on the current literature, there is in general no role for a SNB in DCIS. A SNB should only be considered in patients with an excisional biopsy diagnosis of high risk DCIS (grade III with palpable mass or large tumour area by imaging) as well as in patients undergoing mastectomy after a core or excisional biopsy diagnosis of DCIS, although SNB may be contraindicated in many of the latter patients because of lesion size and/or multifocality. Even in these patients the value of a positive SN, containing mostly isolated tumour cells, is questionable.

Background: The primary role of sentinel lymph node (SLN) mapping in colon cancer is to increase the accuracy of nodal staging by identifying those lymph nodes with the greatest potential for harbouring metastatic disease. Ultrastaging techniques aim to identify the otherwise undetected metastases. Until now, no consensus exists as to the most optimal procedure in patients with colon cancer., Methods: A systematic literature search on the value of different SLN mapping techniques in patients with colon cancer was performed using the electronic search engine PubMed. Prospective studies published before 1 December 2005 were included and further articles were selected by cross-referencing. The results of different techniques using either blue dye or radiocolloid, were investigated., Results: The literature search yielded 17 relevant articles. SLN mapping using blue dye was described in 15 studies. Two studies reported the results of SLN mapping using a combination of blue dye and radiocolloid. The reported results on identification rate varied between 71 and 100%. Accuracy rates were between 78 and 100%, sensitivity rates between 25 and 100% and true upstaging rates between 0 and 26%. The results were not affected by the addition of radiocolloid to blue dye., Conclusions: Sentinel lymph node mapping in patients with colon cancer remains an experimental procedure with varying results. Further evaluation may lead to a standardized technique that offers the potential for significant upstaging of stage II patients. This may have important implications as to tailor adjuvant chemotherapeutic regimens in these patients.

Background: The need for routine axillary lymph node dissection (ALND) in patients with invasive breast cancer and low-volume sentinel node (SN) involvement is questionable. Accurate prediction of second echelon lymph node involvement could identify those patients most likely to benefit from ALND., Methods: A consecutive series of 317 patients with invasive breast cancer and a tumor positive axillary SN followed by ALND was reviewed. Clinicopathologic features of the primary tumor and the SN were assessed as possible predictors of second echelon lymph node involvement., Results: Second echelon metastases were found in 116/317 cases (36.6%). Frequency of second echelon lymph node involvement in patients with isolated tumor cells (ITC, N=23), micro- (N=101) and macrometastases (N=193) was 13%, 20% and 48%, respectively (p<0.001). Based on the area % of SN occupied by tumor no subgroup of patients could be selected with less than 20% second echelon lymph node involvement. However, none of the patients with SN ITC or micrometastases and a primary tumor size

Purpose: We determined prostate perfusion in 18 patients with locally advanced prostate carcinoma treated with a combination of external beam irradiation and regional (10) or interstitial (8) hyperthermia., Materials and Methods: Perfusion values were calculated from temperature elevations due to constant applied power and from transient temperature measurements after a change in applied power. Student's t test was used for comparing perfusion values with time and in the 2 groups., Results: At the start of regional hyperthermia treatment mean estimated perfusion plus or minus standard deviation was 10 +/- 8 ml./100 gm. per minute. At the end of treatment mean perfusion was increased to 14 +/- 2 ml./100 gm. per minute (p <0.01). Achieved thermal parameters were a mean temperature of at least 40.3C +/- 0.6C in 90% of the prostate, 40.9C +/- 0.6C in 50% and a mean maximum temperature of 41.6C +/- 0.6C. At the end of interstitial hyperthermia treatment estimated mean perfusion was 47 +/- 5 ml./100 gm. per minute, which was significantly different compared with the end of regional hyperthermia (p < 0(-7) ). Mean temperature was at least 39.4C +/- 0.9C in 90% of the prostate and 41.8C +/- 1.6C in 50%, while mean maximum temperature was 53.1C +/- 6.3C. Systemic temperature increased during regional hyperthermia up to 38.6C, whereas during interstitial hyperthermia body temperature was not elevated., Conclusions: During interstitial hyperthermia perfusion values are higher than during regional hyperthermia. Hyperthermia causes increased prostate perfusion.

The study is based upon 80 patients, suspected of having recurrent laryngeal cancer, who underwent an 18F-FDG PET study on a coincidence camera and a laryngoscopic biopsy under general anaesthesia. The potential value of 18F-FDG PET in the detection of local relapses of laryngeal cancer after radiotherapy by use of a coincidence camera was prospectively assessed, and a cost-effectiveness analysis was performed retrospectively. The effectiveness of 18F-FDG PET is reflected in sensitivity and specificity, positive predictive value (PPV) and negative predictive value (NPV) using comparison with the biopsy results as a gold standard. In case of a negative biopsy result, follow-up was continued for a minimum of one year. The results showed a sensitivity of 100%, a specificity of 85%, a PPV of 87%, and a NPV of 100%. Costs per patient of a 18F-FDG PET scan were 682 euro, whereas the saved costs by reducing CT-scans and panendoscopies were 618 euro. In this scenario implementation of 18F-FDG PET scintigraphy in the detection of recurrent laryngeal cancer has additional costs of 64 euro per patient. However, panendoscopy related complications, and potential improvement in quality of life due to early detection of recurrent disease were not taken into account in this study. In conclusion, the technical efficacy of 18F-FDG PET in the detection of recurrent laryngeal cancer is high. 18F-FDG PET is more accurate than CT, and in addition the cost-effectiveness ratio of 18F-FDG PET lies within an acceptable range and has further improvement potential when a quality of life factor is included in a prospective cost-effectiveness analysis.