Value of 3D mapping-guided endomyocardial biopsy in cardiac sarcoidosis: Case series and narrative review on the value of electro-anatomic mapping-guided endomyocardial biopsies.

AIM: Integration of endomyocardial biopsy (EMB) in the diagnostic workup of cardiac sarcoidosis (CS) is under-recognized in current clinical practice, since capturing focal granulomas is challenging. Our aim was to describe our experience with electro-anatomic mapping (EAM)-guided EMB and provide a comprehensive review of the literature. METHODS AND RESULTS: Five patients (age 49.4 ± 11.4) with suspected CS underwent EAM-guided EMB in Isala Heart Center (Zwolle, the Netherlands) between 2017 and 2019. In all patients, a 3D bipolar voltage map (<0.5-1.5 mV) and unipolar voltage map (LV < 8.3 mV, RV < 5.5 mV) was created using a high-density mapping catheter. The bioptome was connected to the mapping system to guide targeted EMB. Biopsy samples (2-9 samples) were taken from both LV and RV sites, guided by EAM and areas with abnormal electrograms, without complications. CS diagnosis was based on EMB in 2/5 patients. A granuloma was captured in one patient at the LV basal septum with normal bipolar and abnormal unipolar voltage. All patients with delayed enhancement on cardiac magnetic resonance, revealed fibrosis in the biopsy sample. In one patient with suspected isolated cardiac sarcoidosis, diagnosis could not be confirmed by histopathology analysis, while unipolar voltage mapping was abnormal and diastolic potentials were present. Literature search revealed 7 reports (18 patients) describing EAM-guided EMB in CS patients, with 100% of the EMB taken form the RV. CONCLUSION: Unipolar voltage mapping may be superior to target active inflamed tissue and should be evaluated in future research regarding EAM-guided EMB in CS.

Influence of coronary calcification on hyperemic response during fractional flow reserve measurements.

AIM: During invasive fractional flow reserve (FFR) adenosine and nitrates are used to obtain maximal hyperemia. Severe coronary artery calcification (CAC) is associated with impaired vasodilation. We investigated the hyperemic response during FFR in vessels with severe versus mild CAC. METHODS AND RESULTS: We retrospectively selected 236 patients who underwent both CAC scoring and invasive FFR. FFR was performed in 304 vessels with intermediate stenoses. Delta (Δ) FFR, the pressure gradient before the administration of adenosine minus FFR after the administration of adenosine, was used to investigate the hyperemic response. Mean age of the total population was 65 ±â€¯10 years, 65% was male. Median CAC score was 510 (range 0 to 6141). Mean pressure gradient before the administration of adenosine was comparable in vessels with severe versus mild CAC. FFR was more often ≤0.80 in vessels with severe CAC (p = 0.045). Patients with a large Δ FFR were younger (p = 0.05). There was no association between Δ FFR and severity of calcifications. Regression analysis did not demonstrate an association between CAC score and the hyperemic response (p = 0.49). CONCLUSION: We did not find an association between the severity of CAC and the hyperemic response during invasive FFR.

Radioactive seed localization is the preferred technique in nonpalpable breast cancer compared with wire-guided localization and radioguided occult lesion localization.

OBJECTIVES: Three commonly used techniques for localization of nonpalpable breast cancer are radioactive seed localization (RSL), wire-guided localization (WGL) and radioguided occult lesion localization (ROLL). In this study, we analysed the surgical margins of these three techniques. METHODS: Women diagnosed with nonpalpable breast cancer undergoing breast-conserving surgery with one of the above-mentioned techniques were retrospectively included. The primary outcome parameter was tumour-free margin rate. Secondary outcomes were re-excision rate, recurrence of disease and volume of removed tissue. RESULTS: In total, 272 women were included in whom RSL (n=69), WGL (n=76) or ROLL (n=137) was performed. RSL showed a higher tumour-free margin rate [64 (92.8%)] compared with WGL [51 (67.1%)] and ROLL [113 (82.5%)] (P=0.001). In our multivariable analysis, RSL showed a higher tumour-free margin rate as well compared with WGL (P=0.036) and ROLL (P=0.049). Also, fewer re-excisions were encountered using RSL [5 (7.2%)] compared with WGL [13 (17.1%)] and ROLL [15 (10.9%)] (P=0.171). In 11 patients (WGL n=2, ROLL n=9), recurrence of disease occurred, despite a radical excision. The mean resection volumes were comparable within the three groups. CONCLUSION: RSL results in a higher tumour-free margin rate in nonpalpable breast tumours compared with WGL and ROLL. Therefore, we prefer using RSL in nonpalpable breast tumours.

Effects of Radioiodine Treatment on Salivary Gland Function in Patients with Differentiated Thyroid Carcinoma: A Prospective Study.

Complaints of a dry mouth (xerostomia) and sialoadenitis are frequent side effects of radioiodine treatment in differentiated thyroid cancer (DTC) patients. However, detailed prospective data on alterations in salivary gland functioning after radioiodine treatment (131I) are scarce. Therefore, the primary aim of this study was to prospectively assess the effect of high-activity radioiodine treatment on stimulated whole saliva flow rate. Secondary aims were to study unstimulated whole and stimulated glandular (i.e., parotid and submandibular) saliva flow rate and composition alterations, development of xerostomia, characteristics of patients at risk for salivary gland dysfunction, and whether radioiodine uptake in salivary glands on diagnostic scans correlates to flow rate alterations. METHODS: In a multicenter prospective study, whole and glandular saliva were collected both before and 5 mo after radioiodine treatment. Furthermore, patients completed the validated xerostomia inventory. Alterations in salivary flow rate, composition, and xerostomia inventory score were analyzed. Salivary gland radioiodine uptake on diagnostic scans was correlated with saliva flow rate changes after radioiodine treatment. RESULTS: Sixty-seven patients (mean age ± SD, 48 ± 17 y; 63% women, 84% underwent ablation therapy) completed both study visits. Stimulated whole saliva flow rate decreased after ablation therapy (from 0.92 [interquartile range, 0.74-1.25] to 0.80 [interquartile range, 0.58-1.18] mL/min, P = 0.003), as well as unstimulated whole- and stimulated glandular flow rates (P < 0.05). The concentration of salivary electrolytes was similar at both study visits, whereas the output of proteins, especially amylase (P < 0.05), was decreased. The subjective feeling of dry mouth increased (P = 0.001). Alterations in saliva flow rate were not associated with semiquantitatively assessed radioiodine uptake in salivary glands on diagnostic scans. For the small cohort of patients undergoing repeated radioiodine therapy, we could not demonstrate alterations in salivary parameters. CONCLUSION: We prospectively showed that salivary gland function is affected after high-activity radioiodine ablation therapy in patients with DTC. Therefore, more emphasis should be placed on salivary gland dysfunction during follow-up for DTC patients receiving high-activity radioiodine treatment.

Association between pulmonary vein orientation and atrial fibrillation-free survival in patients undergoing endoscopic laser balloon ablation.

AIMS: Obtaining optimal pulmonary vein (PV) occlusion with the endoscopic laser balloon ablation system (EAS) can be difficult, hypothetically influenced by PV geometry. The aim of this study was to determine the impact of PV orientation on atrial fibrillation (AF)-free survival after PV isolation (PVI) using the EAS. METHODS AND RESULTS: Forty-three patients undergoing a single EAS PVI were included. Left atrial electrocardiogram -triggered computed tomography was performed in all patients prior to PVI. Of all four PVs, the orientation at the insertion in the left atrium was measured in both the transverse and frontal plane and assigned to one of the four orientation groups: ventral-caudal, dorsal-caudal, ventral-cranial, and dorsal-cranial. Mean age was 56 years; 86% had paroxysmal AF. Overall, AF-free survival after a median follow-up of 18.2 months was 51.2%. AF-free survival varied between 21 and 88% depending on left upper PV orientation (P = 0.045). Furthermore, AF-free survival varied between 21 and 86% depending on left lower PV orientation (P = 0.010) and AF-free survival varied between 29 and 88% depending on right lower PV orientation (P = 0.053). No association was found between right upper PV orientation and AF-free survival after EAS PVI (P = 0.794). In multivariate analysis, only left lower PV orientation was associated with AF-free survival [hazards ratio (HR) 10.4, P = 0.019]. CONCLUSION: PV orientation is associated with AF-free survival after EAS PVI. PV orientation assessment may be useful for selecting the most suitable patients for EAS PVI.

Perception of burden experienced during diagnostic tests by melanoma patients with lymph node metastases.

Melanoma patients with lymph node metastases have to deal with diagnostic tests to exclude the presence of distant metastases; results of the tests could have major implications for their prognosis and treatment. There are, however, few studies concerning the patients' psychological issues and perception of diagnostic tests. The aim of this study was to describe the burden of diagnostic tests [radiograph, computed tomography (CT) and positron emission tomography (PET)] experienced by melanoma patients with lymph node metastases. Patients were asked to complete a questionnaire concerning satisfaction and burden experienced during the diagnostic tests. The levels of embarrassment, discomfort and anxiety for the different tests, as well as total scores for each burden were calculated. Logistic regression was used to examine factors associated with the degree of experienced burden. Fifty-nine of the 68 patients completed the questionnaire and the response rate was 87%. The overall mean scores on satisfaction and quality of life were high. More than half of the patients experienced no burden during PET, 65% no burden during computed tomography and 80% no burden during chest radiograph. Patients experienced significantly more discomfort during the PET scan than during the CT (P=0.003). Less burden was experienced (in univariate analysis) by patients who were more satisfied. The overall experienced burden by patients is low and should therefore not interfere with primary choice for a diagnostic test based on accuracy, costs and percentage of patients upstaged. Attention should be paid in explaining the procedure and answering questions of the patients to reduce burden.

Level of fluorodeoxyglucose uptake predicts risk for recurrence in melanoma patients presenting with lymph node metastases.

BACKGROUND: The incidence of malignant melanoma has increased. Identification of additional prognostic factors may allow the development of individualized strategies. This multivariate analysis was undertaken to evaluate the potential role of the standard uptake value (SUV) in predicting disease-free and overall survival in melanoma patients with lymph node metastases. METHODS: All melanoma patients with palpable lymph node metastases who where referred for a fluorodeoxyglucose positron emission tomography scan were eligible. The SUV in the lymph node metastasis was calculated. Data were analyzed (Kaplan-Meier), and differences in cumulative survival and the disease-free rate were assessed (log-rank test). Univariate and multivariate analyses (Cox proportional hazard model) were performed to determine independent prognostic factors. RESULTS: There was no statistical difference in survival for the 38 patients with a high or low SUVmean (P = .11). However, a significant difference was found in disease-free survival (P = .03). Ulceration of the primary melanoma (P = .023) was an independent predictor of survival. For the disease-free survival, multivariate Cox regression showed adjuvant radiation (P = .001), localization of the primary melanoma (P = .017), and a high SUVmean (P = .009) as independent prognostic factors. CONCLUSIONS: Disease-free survival of melanoma patients was prolonged in those with a low SUVmean value (P = .03) in their lymph node metastasis, as compared with those with a high SUVmean. However, this difference was not found for overall survival. In multivariate analysis, high SUVmean was an independent prognostic factor (P = .009) for disease-free survival. Prospective research should determine whether patients with a high FDG uptake in melanoma lymph node metastases could benefit from adjuvant radiation treatment or chemotherapy.

Does sentinel lymph node biopsy in cutaneous head and neck melanoma alter disease outcome?

BACKGROUND AND OBJECTIVES: In the head and neck region, value, reliability, and safety of sentinel lymph node biopsy (SLNB) have not yet been determined conclusively. The aim of study was to assess impact of SLNB on disease outcome in cutaneous head and neck melanoma. METHODS: Thirty-six patients with a clinically node-negative head and neck melanoma, > or =1.0 mm Breslow thickness, participated in a prospective study from 1995 to 2005. Sentinel lymph node (SLN) tumor-positive patients underwent completion lymphadenectomy. SLN tumor-negative patients underwent clinical monitoring. Median follow-up was 54 (range 10-114) months. Recurrence-free and overall survival curves were constructed by Kaplan-Meier. RESULTS: SLNs could be identified in 33 patients (92%). In 7 patients (21%) the SLN was tumor-positive. In 1 patient (13%) the SLNB was false-negative. In 17 patients (47%) SLNs could be identified in the parotid region (success rate parotid region 100%). This study showed no significant difference in recurrence-free and overall survival between patients with tumor-positive and tumor-negative SLN. CONCLUSIONS: The safety and accuracy of SLNB in the neck and parotid nodal basins were similar to those in non-head and neck sites. However, the technique is technically demanding in this region. In this small series SLNB did not alter disease outcome.

Implications of mediastinal uptake of 131I with regard to surgery in patients with differentiated thyroid carcinoma.

BACKGROUND: Findings of mediastinal uptake of 131I after surgical treatment for differentiated thyroid carcinoma (DTC) are common, especially in young patients. Given the frequency of false-positive findings, a protocol for diagnostic and therapeutic strategies would be useful. With the goal of accurately selecting management strategies, the authors analyzed their data and data found elsewhere in the literature for correlations with the incidence of mediastinal 131I uptake and with treatment for patients exhibiting such 131I uptake. METHODS: All patients with DTC who were treated between 1978 and 2000 at Groningen University Hospital (Groningen, The Netherlands) and who received adjuvant 131I ablation therapy were included in the current analysis, which involved retrospective review of all relevant data. RESULTS: Five hundred four patients with DTC initially underwent total thyroidectomy, with additional 131I ablation performed for 489 of these patients. In 48 of 489 patients (9.8%), 131I uptake was seen in the mediastinum on a posttreatment scan. Analysis of those 48 patients and of cases in the literature demonstrated that serum thyroglobulin levels, risk status, and the presence of thymus on radiologic images were important in the surgical decision-making process. CONCLUSIONS: Mediastinal uptake of 131I on posttreatment scans was found in approximately 10% of patients after total thyroidectomy for DTC. Based on the current data and the data presented in the literature, the authors developed a flow chart for determining appropriate treatment strategies, which included mediastinal dissection for high-risk patients and for patients with serum thyroglobulin levels > 10 ng/mL.

Detection and grading of soft tissue sarcomas of the extremities with (18)F-3'-fluoro-3'-deoxy-L-thymidine.

PURPOSE: The aim of the study was to investigate the feasibility of (18)F-3'-fluoro-3'-deoxy-L-thymidine positron emission tomography (FLT-PET) for the detection and grading of soft tissue sarcoma (STS). EXPERIMENTAL DESIGN: Nineteen patients with 20 STSs of the extremities were scanned, using attenuation corrected whole-body FLT-PET. Standardized uptake values (SUVs) and tumor:nontumor ratios (TNTs) were compared with histopathological parameters using French and Japanese grading systems. RESULTS: Mean SUV, maximal SUV, and TNT could differentiate between low-grade (grade 1; n = 6) STS and high-grade (grade 2 and 3; n = 14) STS according to the French grading system (P = 0.001). Mean SUV, max SUV, and TNT correlated with mitotic score, MIB-1 score, the French and Japanese grading system (* = 0.550-0.747). CONCLUSIONS: FLT-PET is able to visualize STS and differentiate between low-grade and high-grade STS. The uptake of FLT correlates with the proliferation of STS.

3'-18F-fluoro-3'-deoxy-L-thymidine: a new tracer for staging metastatic melanoma?

UNLABELLED: In this study, the feasibility of 3'-(18)F-fluoro-3'-deoxy-L-thymidine PET ((18)F-FLT PET) for staging patients with clinical stage III melanoma was investigated. METHODS: Ten patients with melanoma and metastases to the locoregional draining lymph nodes, clinical stage III-based on physical examination, chest radiography, lactate dehydrogenase, and histopathologic confirmation-underwent a whole-body (18)F-FLT PET scan 1 h after injection of a median 400-MBq dose (range, 185-430 MBq) of (18)F-FLT. All (18)F-FLT PET lesions were verified using the American Joint Committee on Cancer Staging System, which includes physical examination, spiral CT, ultrasound, chest radiography, and histopathologic examinations. Size and mitotic rate of metastatic lymph nodes and skin metastases were determined. RESULTS: All histopathologic samples and (18)F-FLT PET lesions were categorized over anatomic regions and correlated. All locoregional metastases were correctly visualized by (18)F-FLT PET. Region-based sensitivity for detection of lymph node metastatic disease was 88%. There were 3 true-negative and 2 false-positive lesions. The detection limit for lymph node metastases appeared to be approximately 6 mm or a mitotic rate of 9 mitoses per 2 mm(2). Two patients were upstaged by (18)F-FLT PET, which was confirmed by CT. In 3 patients, (18)F-FLT PET detected a total of 3 additional lesions with therapeutic consequences, without influencing staging. These lesions were initially missed by clinical staging. CONCLUSION: (18)F-FLT PET seems promising for (re)staging purposes in clinical stage III melanoma. Further research is needed, in which (18)F-FLT PET should be compared with (18)F-FDG PET.

Bone metastases in carcinoid tumors: clinical features, imaging characteristics, and markers of bone metabolism.

UNLABELLED: The purpose of this study was to describe the clinical presentation of bone metastases in patients with carcinoid tumors and to determine the diagnostic value of imaging techniques and markers of bone metabolism. METHODS: This retrospective study was performed on the entire group of patients with carcinoid tumors treated in our hospital from January 1992 to May 1999. Only patients with metastasized tumors were included. RESULTS: Eleven of 90 patients (12%) (95% confidence interval [CI], 5%-19%) with a metastasized carcinoid tumor had symptomatic bone metastases. All bone metastases occurred in 55 patients with midgut carcinoids (20%; 95% CI, 9%-31%). Plain radiography had a sensitivity of 44% (95% CI, 12%-76%); MRI, 100% (95% CI, 61%-100%); bone scintigraphy, 90% (95% CI, 72%-100%); and octreotide scintigraphy, 60% (95% CI, 35%-93%). In 9 patients, both octreotide scintigraphy and bone scintigraphy were performed. Of 45 bone lesions, 22 (49%) were visualized by both modalities, 13 (29%) were visualized with octreotide scintigraphy but not with bone scintigraphy, and 10 (22%) were visualized with bone scintigraphy but not with octreotide scintigraphy. In 2 patients, octreotide scintigraphy and bone scintigraphy provided complementary results. Markers of bone metabolism could not discriminate carcinoid patients from those without bone metastases. The markers of bone metabolism did not reflect the osteolytic or osteoblastic appearance of metastases. CONCLUSION: Pain is the principal symptom of bone metastases in patients with carcinoid tumors. Plain radiography and markers of bone metabolism do not contribute to the diagnosis of bone metastases. MRI has a high sensitivity for bone metastases. Both bone scintigraphy and octreotide scintigraphy have acceptable sensitivity and can provide complementary results.

AL amyloidosis treated with induction chemotherapy with VAD followed by high dose melphalan and autologous stem cell transplantation.

High dose melphalan (HDM) followed by reinfusion of autologous blood stem cells (ASCT) has been applied in AL amyloidosis. Vincristine, doxorubicin, and dexamethasone (VAD) rapidly decrease light chain production in multiple myeloma. In a Phase I/II study of VAD followed by HDM and ASCT in AL amyloidosis, toxicity, feasibility, and response to this regimen were evaluated. Over a 5-year period 38 patients with AL amyloidosis were seen of which 12 out of 18 eligible patients participated in the study. VAD induced a distinct clonal response in 50% (6/12) of the patients, but without clinical improvement. In 11 patients HDM and ASCT was applied. Six months after ASCT 78% (7/9) of the surviving patients showed partial clonal response and none responded completely. Clinical condition evidently improved in 67% (6/9) of survivors, whereby clonal response, clinical response, performance score, and SAP scintigraphs were concordant. Therefore a complete clonal response is not a prerequisite for clinical improvement. With median follow-up after ASCT of 25 months, 75% of the study group patients were alive. Mortality was strongly depending on the number of organs involved Patients treated with HDM and ASCT had better survival than those not eligible (P < 0.0005).