Coronary microvascular function in athletes with abnormal exercise test results.

AIMS: In asymptomatic athletes, abnormal exercise test (ET) results have a poor positive predictive value. It is unknown whether abnormal ET results in the absence of obstructive coronary artery disease (CAD) are related to coronary microvascular dysfunction. It is also unknown whether they should be considered false-positive ET results or a consequence of physiological adaptation to sport. In our study, we evaluated whether athletes with abnormal ET results and documented myocardial ischaemia in the absence of obstructive CAD have an attenuated microvascular function and whether coronary microvascular dysfunction is related to endothelial dysfunction. METHODS AND RESULTS: Nine athletes with concordant abnormal ET and myocardial perfusion scintigraphy (MPS) results without obstructive CAD were compared with age- and gender-matched individuals with a low-to-intermediate a priori risk of CAD. Coronary flow reserve was assessed by Rubidium-82 positron emission tomography (PET) imaging. Endothelin­1 concentrations were measured to evaluate endothelial function. Coronary flow reserve was significantly lower in athletes (3.3 ± 0.8 versus 4.2 ± 0.6, p = 0.014 respectively). Endothelin­1 levels were significantly higher in athletes (1.3 ± 0.2 pg/ml versus 1.0 ± 0.2 pg/ml, p = 0.012 respectively). There was no correlation between endothelin­1 concentrations and mean global coronary flow reserve (r = 0.12). CONCLUSION: Athletes with abnormal ET and MPS outcomes indicative for myocardial ischaemia and no obstructive CAD have a lower coronary flow reserve compared with non-athletes with low-to-intermediate a priori risk of CAD, suggesting an attenuated coronary microvascular function. Higher endothelin­1 concentrations in athletes suggest that endothelial-dependent dysfunction is an important determinant of the attenuated microvascular function.

Design and rationale of the efficacy of spinal cord stimulation in patients with refractory angina pectoris (SCRAP) trial.

BACKGROUND: The use of spinal cord stimulation (SCS) in patients with refractory angina pectoris (RAP) is still under debate. Studies up to date have shown a positive effect with an improvement in quality of life. However, no double blinded randomized controlled trials have been performed. HYPOTHESIS & METHODS: The objective of this trial is to investigate if high density SCS leads to a significant reduction in the amount of myocardial ischemia in patients with RAP. Eligible patients must meet the criteria for RAP, have proven ischemia and a positive transcutaneous electrical nerve stimulator treadmill test. Patients who meet the inclusion criteria will receive an implanted spinal cord stimulator. Patients receive 6 months of high density SCS and 6 months of no stimulation using a cross-over design. The order of the treatment options is determined using randomization. The primary endpoint is the effect of SCS measured by the change in percentage of myocardial ischemia using myocardial perfusion positron emission tomography scan. Key secondary endpoints are patient related outcome measures, major cardiac adverse events and safety endpoints. The follow-up period is 1 year for the primary and key secondary endpoints. RESULTS: The SCRAP trial began enrollment on December 21, 2021 and is set to complete the primary assessments in June 2025. To date, January 2, 2023, 18 patients have been enrolled in the study and 3 patients have completed the 1-year follow-up. CONCLUSIONS: The SCRAP trial is an investigator-initiated, single-center, double-blind, placebo-controlled, and cross-over randomized controlled trial investigating the efficacy of SCS in patients with RAP. (ClinicalTrials. gov Identifier: NCT04915157).

Incidence of axillary recurrence in 113 sentinel node negative breast cancer patients: a 3-year follow-up study.

BACKGROUNDS/AIMS: This study evaluates the 3-year follow-up period and recurrence rate in patients with a negative sentinel node biopsy (SNB) without an additional axillary dissection (ALND). METHODS: Between January 2000 and March 2002, 197 patients with an invasive breast cancer and clinically negative axillary nodes underwent a sentinel node biopsy. One hundred and thirteen patients were included in our study. The follow-up consisted of clinical examination every 3 months in the first year, followed by every 6 months after the first year. A mammography was obtained annually. Attention was paid to loco-regional recurrence, including axillary recurrence, and distant metastases. RESULTS: The mean duration of follow-up was 37.5 months (range 24-54). In this period, one patient was diagnosed with an axillary recurrence and one patient developed a supraclavicular lymph node metastasis. Two patients developed a second primary breast cancer in the contralateral breast. No patients were diagnosed with distant metastasis. CONCLUSION: These 3 year follow-up results suggest that SNB is a procedure with a low clinical recurrence rate, which can replace, when strict criteria are met, ALND if the sentinel node is negative.

A prospective validation study of sentinel lymph node biopsy in multicentric breast cancer: SMMaC trial.

BACKGROUND: Multicentric breast cancer is often considered a contra-indication for sentinel lymph node (SLN) biopsy due to concerns with sensitivity and false negative rate. To assess SLN feasibility and accuracy in multicentric breast cancer, the multi-institutional SMMaC trial was conducted. METHODS: In this study 30 patients with multicentric breast cancer and a clinically negative axilla were prospectively included. Periareolar injection of radioisotope and blue dye was administered. In all patients SLN biopsy was validated by back-up completion axillary lymph node dissection. RESULTS: the SLN was successfully identified in 30 of 30 patients (identification rate 100%). The incidence of axillary metastases was 66.7% (20/30). The false negative rate was 0% (0/20) and the sensitivity was 100% (20/20). The negative predictive value was 100% (10/10). CONCLUSION: SLN biopsy in multicentric breast cancer seems feasible and accurate and should therefore be considered in patients with multicentric breast cancer and clinically negative axilla.

Discordance between number of scintigraphic and perioperatively identified sentinel lymph nodes and axillary tumour recurrence.

BACKGROUND: In breast cancer, sentinel node biopsy is considered the standard method to assess the lymph node status of the axilla. Preoperative identification of sentinel lymph nodes (SLN) is performed by injecting a radioactive tracer, followed by lymphoscintigraphy. In some patients there is a discrepancy between the number of lymphoscintigraphically identified sentinel nodes and the number of nodes found during surgery. We hypothesized that the inability to find peroperatively all the lymphoscintigraphically identified sentinel nodes, might lead to an increase in axillary recurrence because of positive SLNs not being removed. METHODS: Patients who underwent sentinel node biopsy between January 2000 and July 2010 were identified from a prospectively collected database. The number of lymphoscintigraphically and peroperatively identified sentinel nodes were reviewed and compared. Axillary recurrences were scored. RESULTS: 1368 patients underwent a SLN biopsy. Median follow up was 58.5 months (range 12-157). Patient and tumour characteristics showed no significant differences. In 139 patients (10.2%) the number of radioactive nodes found during surgery was less than preoperative scanning (group 1) and in 89.8% (N = 1229) there were equal or more peroperative nodes identified than seen lymphoscintigraphically (group 2). In group 1, 0/139 patients (0%) developed an axillary recurrence and in the second group this was 25/1229 (2.0%) respectively. No significant difference between groups regarding axillary recurrence, sentinel node status and distant metastasis was found. CONCLUSION: Axillary recurrence rate is not influenced by the inability to remove all sentinel nodes during surgery that have been identified preoperatively by scintigraphy.

The value of sentinel lymph node biopsy in ductal carcinoma in situ (DCIS) and DCIS with microinvasion of the breast.

AIM: Ductal carcinoma in situ (DCIS) refers to the preinvasive stage of breast carcinoma and should not give axillary metastases. Its diagnosis, however, is subject to sampling errors. The role of sentinel lymph node biopsy (SLNB) in management of DCIS or DCISM (with microinvasion) remains unclear. The purpose of this study was to review our experience with SLNB in DCIS and DCISM. METHODS: A review of 51 patients with a diagnosis of DCIS (n=45) or DCISM (n=6), who underwent SLNB and a definitive breast operation between January 1999 and December 2006, was performed. RESULTS: In 10 patients (19.6%) definitive histology revealed an invasive carcinoma. SLN (micro)metastases were detected in 5 out of 51 patients, of whom 2 had a preoperative diagnosis of grade III DCIS and 3 of DCISM. Three patients (75%) had micrometastases (< 2 mm) only. In 2 patients, histopathology demonstrated a macrometastasis (> 2 mm). All 5 patients underwent axillary dissection. No additional positive axillary lymph nodes were found. CONCLUSIONS: In case of a preoperative diagnosis of grade III DCIS or a grade II DCIS with comedo necrosis and DCIS with microinvasion, an SLNB procedure has to be considered because in almost 20% of the patients an invasive carcinoma is found after surgery. In this case the SLNB procedure becomes less reliable after a lumpectomy or ablation has been performed. SLN (micro)metastases were detected in nearly 10% of the patients. The prognostic significance of individual tumour cells remains unclear.

Towards quality assurance of the sentinel node procedure in malignant melanoma patients: a single institution evaluation and a European survey.

The status of the regional lymph node (LN) is a critical component in staging patients with malignant melanoma. Biopsy of the first tumour-draining LN (sentinel node, SN) may replace routine elective LN dissection. However, until now, the applied methods have differed widely. Therefore, the aim of this study was to formulate recommendations for the pre-operative identification and intra-operative retrieval of the SN. We present the results of an independent survey of the clinical practice of the SN procedure via a postal questionnaire among 136 nuclear physicians in different institutes throughout 16 European countries. Moreover, the results of the SN procedure in our institution in an open prospective intervention trial in 80 patients with malignant melanoma without palpable LNs are also presented. In our protocol, on average, 6 h prior to surgery, 80 MBq technetium-99m nanocolloid was injected intracutaneously around the circumference of the diagnostic excision scar of the primary melanoma. No additional blue dye procedure was used to judge the accuracy of the radioguided SN procedure on its own. For successful identification of the radiolabelled SN, dynamic and static images were performed and the skin projection of the detected SN was marked with a cobalt-57 source. For intra-operative mapping a hand-held gamma probe was used. Forty of the 83 respondents of the European-wide questionnaire (48%) performed the SN procedure. Although many different regimens are used, the following recommendations could be deduced for the SN procedure in patients with malignant melanoma and non-palpable LNs: (1) local, intradermal injection of 40 MBq 99mTc-nanocolloid around the diagnostic excision scar of the primary melanoma; (2) two-phase LS: dynamic imaging (20 frames of 60 s, 128x128 matrix, LEAP collimator) followed by static images 1-2 h later (180 s per record); (3) intra-operative retrieval of the SN with a gamma probe; (4) histopathological examination of the SN on serial sections. In our trial, surgical retrieval of the SN was successful in 95% of the cases. Dynamic lymphoscintigraphy (LS) contributed to the SN procedure by showing anatomically unpredictable lymph flow to extra-regional SNs (10% of the patients in this study) and multiple SNs. Of the 77 retrieved SNs, 13 contained metastatic disease (17%). Consequently, these patients underwent a formal LN dissection of the affected basin. In conclusion, the SN concept is a rational approach to select patients who could, theoretically, benefit from early LN dissection of the affected basin. Standardisation of the SN procedure will improve the results of this approach, and could be useful for quality control and for making comparisons with other countries in coming years.