Reduced increase of calcium scores using breath-hold in left-sided whole breast irradiation.

PURPOSE: In this prospective longitudinal study, Coronary Artery Calcium (CAC) scores determined before the start of whole breast irradiation were compared with those determined 7 years afterwards. The aim was to examine whether the use of a breath-hold (BH) technique is associated with less increase of CAC scores. METHODS AND MATERIALS: Changes in CAC scores were analysed in 87 breast cancer patients. The results of the following groups were compared: patients receiving right (R) or left-sided radiotherapy using free breathing (L-FB) with those receiving left-sided radiotherapy with BH (L-BH). We compared the changes of CAC scores between these groups over time, testing the hypothesis that a significantly reduced increase of calcium scores is observed when using BH. RESULTS: For L-BH cases, when compared with L-FB cases, for overall as well as for Left Anterior Descending coronary artery (LAD) CAC scores, we noted significantly less increased CAC scores (p < 0.01). This effect of BH was even more striking in the group with CAC scores >0 at baseline. The attenuated increase over time of CAC scores in the L-BH group was robust to correction for age and statin use (p < 0.05). CONCLUSION: After a median follow-up of 7.4 years, we found significantly less increased CAC scores when using BH. This is a relevant finding since higher levels of CAC scores are associated with higher probabilities of coronary artery events. Moreover, it underlines the rationale for the use of BH in left-sided whole breast irradiation.

Local progression and pseudo progression after single fraction or fractionated stereotactic radiotherapy for large brain metastases. A single centre study.

PURPOSE: The 1-year local control rates after single-fraction stereotactic radiotherapy (SRT) for brain metastases > 3 cm diameter are less than 70%, but with fractionated SRT (FSRT) higher local control rates have been reported. The purpose of this study was to compare our treatment results with SRT and FSRT for large brain metastases. MATERIALS AND METHODS: In two consecutive periods, 41 patients with 46 brain metastases received SRT with 1 fraction of 15 Gy, while 51 patients with 65 brain metastases received FSRT with 3 fractions of 8 Gy. We included patients with brain metastases with a planning target volume of > 13 cm(3) or metastases in the brainstem. RESULTS: The minimum follow-up of patients still alive was 22 months. Comparing 1 fraction of 15 Gy with 3 fractions of 8 Gy, the 1-year rates of freedom from any local progression (54% and 61%, p = 0.93) and pseudo progression (85% and 75%, p = 0.25) were not significantly different. Overall survival rates were also not different. CONCLUSION: The 1-year local progression and pseudo progression rates after 1 fraction of 15 Gy or 3 fractions of 8 Gy for large brain metastases and metastases in the brainstem are similar. For better local control rates, FSRT schemes with a higher biological equivalent dose may be necessary.

Introducing a novel approach of network oriented analysis of ERPs, demonstrated on adult attention deficit hyperactivity disorder.

OBJECTIVE: Introducing a network-oriented analysis method (brain network activation [BNA]) of event related potential (ERP) activities and evaluating its value in the identification and severity-grading of adult ADHD patients. METHODS: Spatio-temporal interrelations and synchronicity of multi-sited ERP activity peaks were extracted in a group of 13 ADHD patients and 13 control subjects for the No-go stimulus in a Go/No-go task. Participants were scored by cross-validation against the most discriminative ensuing group patterns and scores were correlated to neuropsychological evaluation scores. RESULTS: A distinct frontal-central-parietal pattern in the delta frequency range, dominant at the P3 latency, was unraveled in controls, while central activity in the theta and alpha frequency ranges predominated in the ADHD pattern, involving early ERP components (P1-N1-P2-N2). Cross-validation based on this analysis yielded 92% specificity and 84% sensitivity and individual scores correlated well with behavioral assessments. CONCLUSIONS: These results suggest that the ADHD group was more characterized by the process of exerting attention in the early monitoring stages of the No-go signal while the controls were more characterized by the process of inhibiting the response to that signal. SIGNIFICANCE: The BNA method may provide both diagnostic and drug development tools for use in diverse neurological disorders.

Human factors for capacity building: lessons learned from the OpenMRS implementers network.

OBJECTIVES: The overall objective of this project was to investigate ways to strengthen the OpenMRS community by (i) developing capacity and implementing a network focusing specifically on the needs of OpenMRS implementers, (ii) strengthening community-driven aspects of OpenMRS and providing a dedicated forum for implementation-specific issues, and; (iii) providing regional support for OpenMRS implementations as well as mentorship and training. METHODS: The methods used included (i) face-to-face networking using meetings and workshops; (ii) online collaboration tools, peer support and mentorship programmes; (iii) capacity and community development programmes, and; (iv) community outreach programmes. RESULTS: The community-driven approach, combined with a few simple interventions, has been a key factor in the growth and success of the OpenMRS Implementers Network. It has contributed to implementations in at least twenty-three different countries using basic online tools; and provided mentorship and peer support through an annual meeting, workshops and an internship program. The OpenMRS Implementers Network has formed collaborations with several other open source networks and is evolving regional OpenMRS Centres of Excellence to provide localized support for OpenMRS development and implementation. These initiatives are increasing the range of functionality and sustainability of open source software in the health domain, resulting in improved adoption and enterprise-readiness. CONCLUSIONS: Social organization and capacity development activities are important in growing a successful community-driven open source software model.

Should internal mammary chain (IMC) sentinel node biopsy be performed? Outcome in 90 consecutive non-biopsied patients with a positive IMC scintigraphy.

INTRODUCTION: Although the status of the regional lymph nodes is an important determinant of prognosis in breast cancer, harvesting sentinel nodes (SN) detected in the internal mammary chain (IMC) is still controversial. AIMS: To determine in how many patients a positive IMC-SN might change the systemic or locoregional adjuvant therapy, with a possible benefit in outcome. PATIENTS AND METHODS: During 6 1/2 years data of T1-2 breast cancer patients, having an SN procedure, were prospectively collected. Our policy was not to explore the IMC even if it was the only localization of an SN. RESULTS: In 86 of 571 patients lymphoscintigraphy showed an IMC-SN. In 64 of these, the axillary SN was negative and only 25 of these patients did not have an indication for adjuvant systemic treatment based on their tumor characteristics. In the literature, IMC metastases are found in 0-10% of axillary negative patients. Routine IMC-SN biopsies would have resulted in an indication for adjuvant systemic therapy in 2-3 of our patients. Four parasternal recurrences were found during a median follow-up of 51 months. CONCLUSIONS: Harvesting IMC-SNs is a procedure of which only a limited number of patients have therapeutical benefit. Even with a thorough selection of patients, the extra morbidity of the procedure should be weighed against the potential benefit for the patient.

[Balanced spinal-epidural anesthesia in pediatric orthopedics].

The problem of spinal epidural anesthesia used in pediatric surgery has been inadequately studied. This investigation was undertaken to develop a balanced spinal epidural anesthesia schedule and to analyze its efficiency during orthopedic operations on the lower extremities in 119 children aged 2 to 16 years. Preference is given to sequential subarachnoidal and epidural space punctures via the same access. Comparative assessment of monitored indices during surgery and a need for postoperative analgesia in the groups of patients with conventional general anesthesia (n = 60) and those who had undergone spinal epidural anesthesia (n = 59) demonstrated a reliable intraoperative and early effective postoperative analgesia after balanced spinal epidural anesthesia.

Reasons for failure to identify positive sentinel nodes in breast cancer patients with significant nodal involvement.

AIM: To analyse causes of failure of sentinel node (SN) procedures in breast cancer patients and assess the role of pre-operative ultrasound examination of the axilla. METHODS: In 138 consecutive clinically node negative breast cancer patients with the primary tumour in situ a SN procedure with radiolabeled colloid and blue dye was performed. Radioactivity in the SN was scored as inadequate or adequate. The axillary lymph node dissection scored for number of involved nodes and presence of extranodal growth. RESULTS: In 53/138 patients, the SN was positive for tumour. Full axillary node dissection revealed that 58/138 were node positive. So in five patients the SN failed to predict true nodal status. In 3/5, the radioactive ratio (SN vs background) was inadequate. All were found to have extensive nodal involvement. The radioactivity ratio was inadequate in 37/138 patients. This ratio was inadequate in 10 of 15 patients with > or =4 positive nodes and 27 of 123 in patients with 0-3 positive nodes (p < 0.001). If extranodal growth was present the radioactive ratio was inadequate in 13 of 18 patients, whilst this was only the case in 24 of 120 patients without extranodal growth or metastases (p < 0.001). Ultrasound (US) examination and US-guided FNAC was able to pre-operatively identify 16 of the 26 patients with four or more metastases in the axilla. CONCLUSIONS: Extensive nodal involvement is an important cause of failure of the sentinel node biopsy. Pre-operative ultrasound examination of the axilla can avoid this in almost two thirds of these patients.

5-Year follow-up of sentinel node negative breast cancer patients.

AIM: To report the long-term results of sentinel node negative breast cancer patients treated without axillary lymph node dissection and the 5-year follow-up results of 149 patients. METHODS: The incidence of axillary-and local recurrences and second ipsilateral primary tumours was evaluated. The added value of annual ultrasound of the treated axilla, being part of the standard follow-up, was also evaluated. RESULTS: After a mean follow-up of 65 months (50-79) axillary recurrences were observed in four patients, local recurrences or ipsilateral second primary tumours were diagnosed in another seven patients. All axillary recurrences were diagnosed because of a palpable axillary mass; ultrasound in combination with fine needle aspiration cytology did not have an added value. CONCLUSION: It can be concluded that the incidence of axillary recurrences after negative SN is much lower than expected. There is no added value of US and FNAC of the axilla in the routine follow-up of SN negative patients.

Radiation protection for the sentinel node procedure in breast cancer.

AIMS: The purpose of our study was to determine the radiation dose for those who are involved in the sentinel node procedure in breast cancer patients and testing of a theoretical model. METHODS: We studied 12 consecutive breast cancer patients undergoing breast surgery, and a sentinel node dissection including an axillary lymph node dissection (ALND). We performed measurements on the surgeon, the assistant, the theatre nurse, the pathologist and his assistant. RESULTS: The measurements on the theatre nurse and both pathologist as his assistant are beneath the detection limit of 10 micro Sv. The highest measured doses are the hands of the surgeon and his assistant (17-61 micro Sv), however the dose limits for hands are higher than for other parts of the body. Taking the dose limits into account the abdominal wall of the surgeon relatively receives the highest dose, with an average of 8.2 micro Sv per procedure. CONCLUSION: Radiation dose levels are less than the established dose limits for (nonexposed) workers if the number of procedures is restricted to about 100/person/year.

Ultrasound-guided fine needle aspiration cytology of axillary lymph nodes in breast cancer patients. A preoperative staging procedure.

Currently, axillary lymph node dissection is increasingly being replaced by the sentinel node procedure. This method is time-consuming and the full immunohistochemical evaluation is usually only first known postoperatively. This study was designed to evaluate the accuracy of preoperative ultrasound-guided fine needle aspirations (FNAs) for the detection of non-palpable lymph node metastases in primary breast cancer patients. We evaluated the material of 183 ultrasound-guided FNAs of non-palpable axillary lymph nodes of primary breast cancer patients. The cytological results were compared with the final histological diagnosis. Ultrasound-guided FNA detected metastases in 44% (37/85) of histologically node-positive patients, in 20% of the total patient population studied. These pecentages are likely to be higher when women with palpable nodes are included. Cytologically false-negative and false-positive nodes were seen in 28 (15%) and three cases (1.6%), respectively. Interestingly 25% (n=7) of the false-negative nodes, revealed micrometastases on postoperative histology. The sensitivity was 57%, the specificity 96%. We conclude that ultrasound-guided FNA of the axillary lymph nodes is an effective procedure that should be included in the preoperative staging of all primary breast cancer patients. Whether lymph nodes are palpable or not, it will save considerable operating time by selecting those who need a complete axillary lymph node dissection at primary surgery and would save a significant number of sentinel lymph node dissections (SLNDs).

Non-sentinel lymph node involvement in patients with breast cancer and sentinel node micrometastasis; too early to abandon axillary clearance.

AIMS: It has been suggested that patients with T1-2 breast tumours and sentinel node (SLN) micrometastases, defined as foci of tumour cells smaller than 2 mm, may be spared completion axillary lymph node dissection because of the low incidence of further metastatic disease. To gain insight into the extent of non-sentinel lymph node (n-SLN) involvement, SLNs and complementary axillary clearance specimens in patients with SLN micrometastases were examined. METHODS: A set of 32 patients with SLN micrometastases was selected on the basis of pathology reports and review of SLNs. Five hundred and thirteen n-SLNs from the axillary clearance specimens were serially sectioned and analysed by means of immunohistochemistry for metastatic disease. Lymph node metastases were grouped as macrometastases (> 2 mm), and micrometastases (< 2 mm), and further subdivided as isolated tumour cells (ITCs) or clusters. RESULTS: In 11 of 32 patients, one or more n-SLN was involved. Grade 3 tumours and tumours > 2 cm (T2-3 v T1) were significantly associated with n-SLN micrometastases as clusters (grade: odds ratio (OR), 8.3; 95% confidence interval (CI), 1.4 to 50.0; size: T2-3 tumours v T1: OR, 15; 95% CI, 2.18 to 103.0). However, no subgroup of tumours with regard to size and grade was identified that did not have n-SLN metastases. CONCLUSIONS: In patients with breast cancer and SLN micrometastases, n-SLN involvement is relatively common. The incidence of metastatic clusters in n-SLN is greatly increased in patients with T2-3 tumours and grade 3 tumours. Therefore, axillary lymph node dissection is especially warranted in these patients. However, because n-SLN metastases also occur in T1 and low grade tumours, even these should be subjected to routine axillary dissection to achieve local control.

Ganglioneuromatous polyposis: a premalignant condition. Report of a case and review of the literature.

A 40-year-old man with ganglioneuromatous polyposis and an aggressive coexisting colorectal cancer is described. Contrary to previous reports, we believe that ganglioneuromatous polyposis should be considered a premalignant condition.

Controlled introduction of the sentinel node biopsy in breast cancer in a multi-centre setting: the role of a coordinator for quality control.

AIMS: It is proposed that sentinel node biopsy should replace axillary lymph-node dissection. We analysed the role of a coordinator in the introduction of the sentinel node biopsy in breast cancer in a multi-centre setting to assure standardization and quality control. METHODS: We included 232 operable breast cancer patients. Part of the procedure was an ultrasound examination of the axilla with fine needle aspiration cytology. The sentinel node was identified with 99m-Technetium and Patent Blue. RESULTS: The results of the procedure, sensitivity and false negativity, were the same for the three participating hospitals. We think this is mostly due to the coordinator who supplied information about the technique, pitfalls and results to all teams. CONCLUSIONS: Our experience regarding the organization aspects of introducing the sentinel node procedure in a multi-centre setting now serves as a model in organizing its application in a much wider number of hospitals.

Multicentre study of ultrasonographically guided axillary node biopsy in patients with breast cancer.

BACKGROUND: Axillary lymph node dissection is still performed as a staging procedure since lymph node status is the most important prognostic factor in patients with breast cancer. Sentinel node biopsy may replace routine axillary lymphadenectomy, especially in patients with small breast cancers. This study investigated whether ultrasonographically guided fine-needle aspiration cytology (FNAC) of the axillary lymph nodes in clinically node-negative patients was an accurate staging procedure to select patients for sentinel node biopsy. METHODS: One hundred and eighty-five consecutive patients were included. All had axillary ultrasonography and detected nodes were categorized according to their dimensions and echo patterns. Ultrasonographically guided FNAC was carried out if technically possible. These results were compared with the results of the sentinel node biopsy and subsequent axillary dissection. RESULTS: In 116 patients no lymph nodes were detected by ultrasonographic imaging. Of 69 patients with visible nodes, 31 had malignant cells on FNAC. There were no false-positive results. Some 87 of 185 patients had axillary metastases on definitive histological examination. Ultrasonography was sensitive in patients with extensive nodal involvement. Failure of the examination was caused by problems learning the method, difficulty in puncturing small lymph nodes and sampling error. CONCLUSION: In patients without palpable axillary nodes, a sentinel node biopsy could be avoided in 17 per cent since ultrasonography combined with FNAC had already diagnosed axillary metastases. The method is particularly valuable in larger breast cancers.

Clinical determinants of ultrasound-guided sclerotherapy outcome. Part I: The effects of age, gender, and vein size.

BACKGROUND: Ablation of the incompetent saphenous vein may be accomplished by either surgical extirpation or ultrasound-guided sclerotherapy (UGS). Clinical guidelines for the selection of suitable candidates for UGS have yet to be established for this relatively new procedure. OBJECTIVE: To assess the effects of age, gender, and vein size on the outcome of UGS. METHODS: UGS was performed on 116 Class C2-6EPASPR limbs with duplex-confirmed saphenofemoral junctional incompetence using 1-mL injectate volumes of 3% sodium tetradecyl sulphate (STS) (15-mL maximum) and Class II compression. Treatment endpoint was persistent vasospasm observed on duplex imaging, with clinical and duplex ultrasound follow-up at 2 weeks, 6 months, and annually for 2 years. RESULTS: Statistical testing showed that only vein size affected recanalization. Age, gender, and vein size all affected the dosage required to achieve vasospasm, but not the clinical recurrence rate. Vein size was larger in males and correlated with age. CONCLUSIONS: Larger doses of STS are required to induce vasospasm in older patients, males, and those with larger veins. Regardless of gender and age, larger veins are more likely to recanalize, but are not necessarily associated with clinical recurrence. Although older patients and males tend to have larger veins, their recanalization rates are similar to younger patients and females when sufficiently higher STS doses are used to induce vasospasm. Ambulatory patients of all ages and either gender may be good candidates for UGS if vasospasm is used as the treatment endpoint. Contrary to prevailing opinion, large vein caliber is not an absolute contraindication for UGS.