Hot dots - which nodes should be removed in sentinel lymph node biopsy for melanoma?

BACKGROUND: Sentinel lymph node biopsy (SLNB) is a critical staging tool for melanoma patients. The optimal number of lymph nodes removed in SLNB remains unclear. In this study, we retrospectively analysed and tested different criteria for selecting sentinel lymph nodes (SLNs) by radiotracer uptake and blue dye, and their impact on nodal staging. We also evaluated the association between SLN tumour burden and radiotracer uptake. METHODS: The study population consisted of melanoma patients undergoing SLNB. During the operation all radioactive and blue nodes were removed and sent for histopathological analysis. The ex vivo radioactive count and presence of blue dye of each node were recorded, and these were correlated with presence and size of metastasis in each SLN. RESULTS: Altogether 175 patients with clinically occult metastasis presented with one or more positive, i.e. metastatic, SLNs. The mean number of lymph nodes removed was 4.5, and the mean number of positive lymph nodes was 1.5 per patient. The most radioactive or hottest node was negative in 38 patients (22%). By removing the hottest node and all nodes with radioactivity >10% of the hottest node, 97% of patients would have been staged correctly. In five patients, metastasis was found solely in a SLN with radioactivity <10% of the hottest node. Of all 267 positive nodes removed, 125 (47%) contained blue dye. Patients with a negative hottest node were associated with lower SLN tumour burden. CONCLUSIONS: By removing the hottest node and all nodes with radioactivity >10% of the hottest node, 97% of patients with SLN metastases are correctly staged with or without using blue dye.

Convolutional neural networks for detection of transthyretin amyloidosis in 2D scintigraphy images.

BACKGROUND: Transthyretin amyloidosis (ATTR) is a progressive disease which can be diagnosed non-invasively using bone avid [99mTc]-labeled radiotracers. Thus, ATTR is also an occasional incidental finding on bone scintigraphy. In this study, we trained convolutional neural networks (CNN) to automatically detect and classify ATTR from scintigraphy images. The study population consisted of 1334 patients who underwent [99mTc]-labeled hydroxymethylene diphosphonate (HMDP) scintigraphy and were visually graded using Perugini grades (grades 0-3). A total of 47 patients had visual grade ≥ 2 which was considered positive for ATTR. Two custom-made CNN architectures were trained to discriminate between the four Perugini grades of cardiac uptake. The classification performance was compared to four state-of-the-art CNN models. RESULTS: Our CNN models performed better than, or equally well as, the state-of-the-art models in detection and classification of cardiac uptake. Both models achieved area under the curve (AUC) ≥ 0.85 in the four-class Perugini grade classification. Accuracy was good in detection of negative vs. positive ATTR patients (grade < 2 vs grade ≥ 2, AUC > 0.88) and high-grade cardiac uptake vs. other patients (grade < 3 vs. grade 3, AUC = 0.94). Maximum activation maps demonstrated that the automated deep learning models were focused on detecting the myocardium and not extracardiac features. CONCLUSION: Automated convolutional neural networks can accurately detect and classify different grades of cardiac uptake on bone scintigraphy. The CNN models are focused on clinically relevant image features. Automated screening of bone scintigraphy images using CNN could improve the early diagnosis of ATTR.

Prognostic Value of 99mTc-HMDP Scintigraphy in Elderly Patients With Chronic Heart Failure.

BACKGROUND: This study evaluated the prevalence and prognostic significance of cardiac transthyretin amyloidosis (ATTR) diagnosed using 99mTc- hydroxymethylene-diphosphonate (99mTc-HMDP) scintigraphy in an elderly heart failure population. METHODS: This retrospective study included 335 patients aged >70 years with heart failure and who underwent 99mTc-HMDP scintigraphy due to non-cardiac reasons in three imaging centres in Finland (Kymenlaakso Central Hospital, Jorvi Central Hospital, and Meilahti University Hospital). A Perugini grade >2 and heart-to-contralateral ratio (H/CL) of ≥1.30 were considered positive for cardiac ATTR. The overall and cardiovascular mortality were obtained from the national statistical service (Statistics Finland). RESULTS: There were 234 deaths, of which 70 were classified as being due to cardiovascular causes during a median follow-up of 1 (1-3) year. Transthyretin amyloidosis was diagnosed in 22 patients (6.6%) using visual analysis and 17 patients using the H/CL ratio (5.1%). Patients with ATTR were older (85±5 vs 80±5 yrs; p=0.002) and had higher N-terminal pro-brain natriuretic peptide (NT-ProBNP) levels (1,451 [813-3,799] vs 6,192 [2,030-8,833] ng/L; p=0.02). Age, bone metastases, and glomerular filtration rate were independent predictors of overall mortality in multivariable analysis. Age, glomerular filtration rate, ≥grade 2 visual cardiac uptake, and H/CL ratio were independent predictors of cardiovascular mortality. CONCLUSIONS: Cardiac uptake suggestive of ATTR was found in 5% of elderly patients with chronic heart failure. The presence of cardiac uptake on bone scintigraphy did not convey independent prognostic value on overall mortality but was independently associated with cardiovascular mortality.

Comparison of reprojected bone SPECT/CT and planar bone scintigraphy for the detection of bone metastases in breast and prostate cancer.

OBJECTIVE: The aim of this study was to compare reprojected bone SPECT/CT (RBS) against planar bone scintigraphy (BS) in the detection of bone metastases in breast and prostate cancer patients. METHODS: Twenty-six breast and 105 prostate cancer patients with high risk for bone metastases underwent 99mTc-HMDP BS and whole-body SPECT/CT, 1.5-T whole-body diffusion-weighted MRI and 18F-NaF or 18F-PSMA-1007 PET/CT within two prospective clinical trials (NCT01339780 and NCT03537391). Consensus reading of all imaging modalities and follow-up data were used to define the reference standard diagnosis. The SPECT/CT data were reprojected into anterior and posterior views to produce RBS images. Both BS and RBS images were independently double read by two pairs of experienced nuclear medicine physicians. The findings were validated against the reference standard diagnosis and compared between BS and RBS on the patient, region and lesion levels. RESULTS: All metastatic patients detected by BS were also detected by RBS. In addition, three metastatic patients were missed by BS but detected by RBS. The average patient-level sensitivity of two readers for metastases was 75% for BS and 87% for RBS, and the corresponding specificity was 79% for BS and 39% for RBS. The average region-level sensitivity of two readers was 64% for BS and 69% for RBS, and the corresponding specificity was 96% for BS and 87% for RBS. CONCLUSION: Whole-body bone SPECT/CT can be reprojected into more familiar anterior and posterior planar images with excellent sensitivity for bone metastases, making additional acquisition of planar BS unnecessary.

Prognostic significance of incidental suspected transthyretin amyloidosis on routine bone scintigraphy.

BACKGROUND: Transthyretin amyloidosis (ATTR) is an occasional incidental finding on bone scintigraphy. We studied its prognostic impact in elderly patients. METHODS: The study population consisted of 2000 patients aged over 70 years who underwent bone scintigraphies with clinical indications in three nuclear medicine departments (Kymenlaakso, Jorvi and Meilahti hospitals) in Finland. All studies were performed using 99mTechnetium labeled hydroxymethylene diphosphonate (HMDP). ATTR was suspected in patients with ≥grade 2 Perugini grade uptake (grade 0-3). Heart-to-contralateral ratio (H/CL) of ≥ 1.30 was considered positive for ATTR. The overall and cardiovascular mortality were obtained from the Finnish National Statistical Service. RESULTS: There were a total of 1014 deaths (51%) and 177 cardiovascular deaths (9%) during median follow-up of 4 ± 2 years. ATTR was suspected in 69 patients (3.6%) of which 54 (2.7%) had grade 2 and 15 (.8%) had grade 3 uptake and in 47 patients (2.4%) by H/CL ratio. In multivariate analyses age, bone metastasis, H/CL ratio and grade 3 uptake were independent predictors of overall and cardiovascular mortality. Grade 2 uptake was a predictor of cardiovascular mortality. CONCLUSIONS: A suspected ATTR as an incidental finding on bone scintigraphy predicts elevated overall and cardiovascular mortality in elderly patients.

Transdermal fentanyl in cachectic cancer patients.

Fentanyl is an opioid with high lipid solubility, suitable for intravenous, spinal, transmucosal and transdermal administration. The transdermal fentanyl patch has become widely used in the treatment of both malignant and non-malignant chronic pain. The absorption of fentanyl from the patch is governed by the surface area of the patch, by skin permeability and by local blood flow. The aim of this study is to find out whether absorption of fentanyl in cachectic patients with cancer-related pain is different from that of normal weight cancer patients. We recruited ten normal weight (mean body mass index (BMI) 23 kg/m(2)) and ten cachectic (mean BMI 16 kg/m(2)) cancer pain patients. A transdermal fentanyl patch with a dose approximately equianalgesic to the patients' previous opioid dose was administered to the upper arm of the patient for 3 days. Prior to patch application, the height, weight and BMI of the patient, as well as upper arm skin temperature, local sweating, thickness of skin fold and local blood flow were measured. Plasma fentanyl concentrations were analyzed from blood samples taken at baseline, 4, 24, 48 and 72 h. Plasma fentanyl concentrations adjusted to dose were significantly lower at 48 and 72 h in cachectic patients than normal weight patients. The cachectic patients had a significantly thinner upper arm skin fold, but no differences were found in local blood flow, sweating, or skin temperature. Absorption of transdermal fentanyl is impaired in cachectic patients compared with that of normal weight cancer pain patients.

Sentinel lymph node biopsy or elective neck dissection for patients with oral squamous cell carcinoma?

Sentinel lymph node biopsy (SNB) seems to be a promising method for staging clinically N0 neck in patients with oral squamous cell carcinoma (OSCC). In the present study, SNB was performed on 46 patients having elective neck dissection (END; six bilateral dissections) for T1-T3N0 OSCC. Sentinel lymph nodes (SLN) were first examined according to only slightly modified standard histopathologic protocol including sections at 1-2 mm intervals and H&E staining. SLN that appeared false negative (i.e. metastatic non-SLN without metastasis in a SLN) after the initial histopathologic examination were further assessed by step sectioning at 150 microm intervals and immunohistochemistry. Of the 47 neck sides with at least one SLN identified, nine contained metastasis in nine patients. After the initial histopathologic examination, SLNs were negative for malignant cells in four out of the nine metastatic neck sides. In one neck side, two metastatic SLNs were detected after the additional meticulous histopathologic work-up of the initially false negative SLNs. Therefore, in three neck sides the SLN did not contain metastasis although there was a metastasis in a non-SLN. In all these three cases with a false negative SLN, only one SLN had been identified. The sensitivity of the method (employing extensive histopathologic work-up) for detection of occult cervical metastasis was 67% (6/9 neck sides). The sensitivity of SNB for detection of occult metastasis seems to be poor in cases where only one SLN can be identified. The results of this study do not entitle us to entirely replace END by SNB in patients with OSCC.

Sentinel lymph node biopsy as an alternative to wait and see policy in patients with small T1 oral cavity squamous cell carcinoma.

CONCLUSION: Although sentinel lymph node (SLN) biopsy is not yet validated for clinical use to replace elective neck dissection in patients with oral squamous cell carcinoma, it can be recommended for patients who do not fulfil the criteria for elective neck treatment according to current treatment protocols. OBJECTIVE: To examine the benefits of SLN biopsy in oral cancer patients who have a small risk for occult metastasis and therefore are not considered candidates for elective neck treatment. PATIENTS AND METHODS: Thirteen consecutive patients with a small T1 oral cavity squamous cell carcinoma, clinically staged NO, and who did not meet the indications for elective neck treatment, underwent SLN biopsy. The SLNs were cut at 1-2 mm intervals and stained with haematoxylin and eosin and cytokeratin AE1/AE3. RESULTS: Histopathological examination of SLNs revealed micrometastases in two patients. A selective neck dissection was performed on these patients and no further metastases were encountered. All patients had a minimum follow-up of 12 months and no cervical or other recurrences were encountered.

Sentinel lymph node mapping using SPECT-CT fusion imaging in patients with oral cavity squamous cell carcinoma.

Lymphoscintigraphic planar imaging is commonly performed to locate the sentinel lymph nodes (SLN) preoperatively. The images are, however, obscure lacking anatomical information and only rough topographical orientation of the SLNs is possible. Image fusion of Single Photon Emission Computed Tomography (SPECT) and Computed Tomography (CT) has been suggested to be an anatomically more precise method for preoperative SLN mapping. In the present study, preoperative lymphoscintigraphic SLN mapping was performed by using a hybrid gamma-camera with CT system (SPECT-CT) in addition to conventional planar lymphoscintigraphy in 15 consecutive patients with squamous cell carcinoma (SCC) of the oral cavity. The planar images were compared to fused SPECT and CT images. SPECT-CT fusion images showed only one SLN that was not detected in planar images. Two SLNs suspected in planar images could be excluded by SPECT-CT. The location of the SLNs could be determined more accurately by SPECT-CT. SPECT-CT fusion imaging was found feasible for preoperative SLN identification in patients with oral cavity SCC. It enables more accurate localisation of the SLNs, but it rarely reveals SLNs, that are not detected on planar images.

Infrainguinal endovascular and bypass surgery for critical leg ischemia in patients on long-term dialysis.

Lower limb revascularization has been shown to be worthwhile for treatment of critical leg ischemia in uremic patients, but poor results are expected in patients on long-term dialysis. We have retrospectively evaluated the results of a series of 21 consecutive patients on long-term dialysis who underwent 20 infrainguinal bypass graft and 5 endovascular procedures for critical leg ischemia to identify factors contraindicating any infrainguinal revascularization attempt in this patient population. At 2-year follow-up, the patency rate was 74%, leg salvage rate was 85%, and survival rate was 23%, whereas 23% of patients were alive with salvaged leg. Patients on hemodialysis achieved better survival outcome than patients on peritoneal dialysis (p = 0.02). Multivariate analysis showed that low serum level of albumin (p = 0.009; p = 0.005) and coronary artery disease (p = 0.0002; p = 0.001) had an adverse effect on the survival rate and on the rate of patients alive with salvaged leg, respectively. Patients without coronary artery disease achieved an alive-with-salvaged-leg rate at 1- and 2-year follow-up of 68% and 41%, respectively, whereas 12% of patients with coronary artery disease survived with salvaged leg after 1 year, but none of them survived with salvaged leg at 2-year follow-up (p = 0.003). In conclusion, infrainguinal revascularization for lower extremity ischemia in dialysis patients is hardly indicated in the presence of coronary artery disease and severe hypoalbuminemia.