Same-day or next-day sentinel node biopsy after lymphoscintigraphy for melanoma using 99m Tc-labelled antimony sulphide colloid.

BACKGROUND: Two recent publications have reported that a shorter interval between preoperative lymphoscintigraphy and sentinel node biopsy (SNB) is associated with improved survival of patients with primary cutaneous melanoma. The aims of this study were to analyse prospectively collected survival data for patients who had SNB on the same day as lymphoscintigraphy or the day after; and to assess tracer migration from sentinel nodes to second-tier nodes after lymphoscintigraphy on the previous day. METHODS: Outcome data were obtained for patients who had lymphoscintigraphy and SNB on the same day (time interval less than 8 h) or the next day (interval more than 16 h). In a separate prospective cohort, same-day and next-day lymphoscintigraphic images of sentinel nodes and second-tier nodes were compared. RESULTS: Following lymphoscintigraphy, 2848 patients had same-day and 3328 had next-day SNB. Survival outcomes did not differ between these groups. In a prospectively studied cohort of 30 patients, none had significant tracer migration from sentinel nodes to second-tier nodes on imaging the following day. CONCLUSION: No difference in survival after same- or next-day sentinel node biopsy is seen when 99m Tc-labelled antimony sulphide colloid is used. This may be because of less tracer migration to second-tier nodes.

ANTECEDENTES: Dos publicaciones recientes han señalado que reducir el intervalo entre la linfografía isotópica preoperatoria y la biopsia del ganglio centinela (sentinel node biopsy, SNB) se asocia con una mejor supervivencia en pacientes con melanoma maligno primario. Los objetivos de este estudio fueron los siguientes: (1) analizar los datos de supervivencia recogidos prospectivamente en pacientes en los que se realiza la SNB el mismo día o al día siguiente de la linfografía isotópica, y (2) evaluar la migración del marcador desde los ganglios centinela a los ganglios de segundo nivel a partir de la linfografía del día anterior. MÉTODOS: Se analizaron los resultados de los pacientes a los que se realizó una linfografía isotópica y la SNB el mismo día (intervalo de tiempo < 8 h) o al día siguiente (intervalo > 16 h). En una cohorte prospectiva diferente, se compararon las imágenes de los ganglios centinela y de los ganglios de segundo nivel en linfografías isotópicas realizadas el mismo día o al día siguiente. RESULTADOS: Tras la linfografía isotópica, se realizó la SNB el mismo día en 2.848 pacientes y al día siguiente en 3.328 pacientes. No hubo diferencias en la supervivencia entre ambos grupos. En una cohorte de 30 pacientes estudiada de forma prospectiva, no hubo migración significativa del trazador de los ganglios centinela a los ganglios de segundo nivel en las imágenes obtenidas al día siguiente. CONCLUSIÓN: La mejor supervivencia que se obtiene cuando se realiza la SNB poco después de la linfografía isotópica podría explicarse por una diferencia en la migración del trazador a los ganglios de segundo nivel entre los dos marcadores utilizados: nanocoloide de albúmina humana o coloide de sulfuro de antimonio, ambos marcados con 99mTc. En este estudio y con este último marcador, no se observó migración a ganglios de segundo nivel durante la noche.

Melanoma patient imaging in the era of effective systemic therapies.

Imaging plays a critical role in the current multi-disciplinary management of patients with melanoma. It is used for primary disease staging, surgical planning, and surveillance in high-risk patients, and for monitoring the effects of systemic or loco-regional therapies. Several different imaging modalities have been utilised in the past. Contemporary imaging practises vary geographically depending on clinical guidelines, physician preferences, availability and cost. Targeted therapies and immunotherapies have revolutionised the treatment of patients with metastatic melanoma over the last few years. With this have come new patterns of disease that were not observed after conventional therapies, and new criteria to assess therapeutic responses. In this article we review the role of imaging for patients with melanoma in the era of effective systemic therapies and discuss likely future developments.

High discordance rates between sub-areolar and peri-tumoural breast lymphoscintigraphy.

OBJECTIVE: To test the hypothesis that sub-areolar (SA) lymphoscintigraphy (LSG) identifies the same sentinel node as peri-tumoural (PT) injections. BACKGROUND: It is commonly believed that all LSG techniques will identify the same sentinel lymph nodes (SLN) draining the breast. Hybrid imaging technology (SPECT/CT) allows accurate identification of the exact location of SLNs. Using SPECT/CT SA and PT LSG techniques were compared. METHOD: In a multi-centre trial 39 patients sequentially underwent LSG (SA followed by PT) separated by 2-7 days. Patients were referred by 4 surgeons to 3 LSG centres, with standardization of isotope (99mTc-antimony sulfide colloid), LSG and SPECT/CT evaluation techniques. LSG were evaluated for SLN concordance and degree of discordance in the axilla and internal mammary nodes (IMN). RESULTS: 39 eligible patients, median age 62 years, were recruited. Successful axillary SLN mapping for SA and PT injection techniques was 87% and 95% respectively. Successful internal mammary SLN mapping occurred with SA and PT LSG in 5% and 36% respectively. Discordance was identified in the IMN (39%) and axilla (21%), with an overall rate of discordance between SA and PT LSG of 56%. CONCLUSIONS: There is a high level of discordance in the localization of SLN by these commonly used LSG injection techniques. This discordance has implications for accuracy of axillary and extra-axillary staging and could impact on patient outcome.

SPECT/CT scans allow precise anatomical location of sentinel lymph nodes in breast cancer and redefine lymphatic drainage from the breast to the axilla.

BACKGROUND: Historical studies of lymphatic drainage of the breast have suggested that the lymphatic drainage of the breast was to lymph nodes lying in the antero-pectoral group of nodes in the axilla just lateral to the pectoral muscles. The purpose of this study was to confirm this is not correct. METHODS: The hybrid imaging method of SPECT/CT allows the exact anatomical position of the sentinel lymph node (SLN) in the axilla to be documented during pre-operative lymphoscintigraphy (LS) in patients with breast cancer. We have done this in a series of 741 patients. The Level I axillary nodes were defined as anterior, mid or posterior. This was related to the anatomical location of the primary cancer in the breast. RESULTS: A SLN was found in the axilla in 97.8% of our patients. Just under 50% of SLNs located in the axilla were not in the anterior group and lay in the mid or posterior group of Level I axillary nodes. There was a SLN in a single node field in 460 patients (63%), two node fields in 261(36%), three node fields in 6 and four node fields in 1 patient. CONCLUSION: Axillary lymphatic drainage from the breast is not exclusively to the anterior (or antero-pectoral) group of Level I nodes. SYNOPSIS: SPECT/CT lymphoscintigraphy shows that the breast does not always drain to the anterior group of Level I lymph nodes in the axilla but may drain to the mid axilla and/or posterior group in about 50% of patients with breast cancer regardless of the location of the cancer in the breast. These data redefine lymph drainage from the breast to axillary lymph nodes.

Internal mammary lymph node metastasis in breast cancer: predictive models to assist with prognostic influence.

BACKGROUND: Metastatic breast cancer in the internal mammary nodes (IMN) indicates a poor prognosis. Several recent epidemiological surveys have determined a reduction in survival for patients with medial compared to lateral sector tumors attributing this to a higher rate of unrecognized IMN metastasis and hence these patients are undertreated with adjuvant therapy.(1-6) AIM: Through mathematical modeling based on large datasets we aim to quantify the impact on survival of IMN metastases at different tumor and axillary stages. METHODS: Mathematical models were created to estimate the survival of patients with and without IMN metastasis. It was assumed that the different rate of survival between medial and lateral sector breast cancers was a result of the differential rate of unrecognized IMN metastases with resultant under-staging and under treatment. We applied these models on a retrospective database analysis from the Surveillance, Epidemiology and End-Results (SEER) registries from 1994 to 2003. RESULTS: The 10-year odds of death (OOD) from breast cancer for patients with medial compared with lateral sector tumors ranged from 1.2 to 1.5 depending on stage. The predicted odds of breast cancer death for patients with unrecognized IMN metastases ranged from 2.4 to 20, with the highest OOD in the groups with small tumors and no axillary node metastasis. CONCLUSIONS: Through modeling we have been able to predict and quantify the significantly worse survival outcomes for patients with undiagnosed IMN metastasis.

Internal mammary node metastasis in breast cancer: predictive models to determine status & management algorithms.

AIM: Internal mammary node (IMN) metastases are an important prognostic factor in breast cancer. However due to difficulty of access, most surgeons ignore these nodes, hence adjuvant treatment decisions may be compromised. Through mathematical modeling based on large datasets this study aims to estimate the current rate of IMN and sentinel node metastasis. METHODS: Models were created to estimate the current rate of axillary and IM sentinel node metastasis. Data from historical extended radical mastectomy series were analyzed to project contemporary rates of IMN metastasis. This information was coupled with derived models and contemporary datasets: a single-institution breast lymphoscintigraphy database (1992-2007) to establish lymphatic anatomy; and the Surveillance, Epidemiology and End-Results (SEER) registries in the US (2000-2003). RESULTS: Rates of IMN metastasis and positive sentinel nodes were estimated and models derived to assist with predicting IMN status in patients. If high definition peritumoral lymphatic mapping were available, the predicted rates of positive sentinel nodes in the axilla (AN) and internal mammary chain (IMN) would be equal. We predicted the overall rate of IMN metastasis is approximately 39% the rate of positive sentinel AN. CONCLUSION: Simplified models and algorithms can predict IMN status.

High-resolution lymphoscintigraphy is essential for recognition of the significance of internal mammary nodes in breast cancer.

BACKGROUND: Sentinel node biopsy (SNB) of internal mammary nodes (IMNs) in breast cancer is controversial. Most centers rarely identify IMN on lymphoscintigraphy but others report up to 45% of cases. Controversy relates to the technique of lymphatic mapping, safety of IMN SNB, the significance of positive IMN, and potential to impact survival. METHODS: Assessment of drainage rates from two unrelated nuclear medicine departments' databases. Review of related literature. RESULTS: High-resolution lymphoscintigraphy results in IMN drainage in one-third of breast cancers. There is a learning curve for the technique. In 1754 consecutive cases, internal mammary drainage occurred in 53% of medial tumors, 37% midline tumors and 24% of lateral tumors (overall 34%). Extended radical mastectomy series also demonstrate the (approximately) 1/3 ratio when comparing IMN positivity rates to axillary node positivity rates (18.8% : 48.3%) and in node-positive patients (31% : 100%). The management altering potential of IMN assessment and potential survival impact are discussed. CONCLUSIONS: IMN mapping gives information that alters management in up to one-third of cases. These rates of IMN drainage are reproducible and reflect lymphatic density and anatomy of the breast. A priority need exists to establish a collaborative clinical trial to clarify the value of IMN assessment.

Computer modeling provides a new tool for clinically diagnosing melanoma spread through the lymphatics.

In this study an anatomically accurate framework is presented to visualize clinical melanoma data in 3D. Sentinel lymph node biopsy (SLNB) data from the Sydney Melanoma Unit (SMU) has been used, where each patient's primary cutaneous melanoma site and corresponding sentinel lymph node locations have been recorded. Anatomically accurate finite element geometries of the skin and lymph nodes have been created using the visible human dataset. SMU's full SLNB database has been mapped from 2D onto this 3D anatomical framework via free-form deformation and projection techniques. Spatial statistical analysis and heat map displays have been calculated and visualized relating melanoma sites on the skin to sentinel lymph node fields. These detailed spatial maps provide the first anatomically accurate link between skin sites and lymphatic drainage. The extension and ongoing application of this work in the clinic is a novel method to capture data for both improved melanoma diagnosis and a better understanding of lymphatic drainage in the body.

Lymphatic mapping of the breast: locating the sentinel lymph nodes.

When the concept of sentinel lymph node biopsy was described in patients with melanoma, researchers quickly started to use lymphatic mapping techniques in breast cancer patients in an attempt to locate the sentinel node in the axilla. We have been performing mammary lymphoscintigraphy in this role for 6 years and have now studied 159 patients. Like others, we have found that most breast cancers (93%) have lymphatic drainage that includes the axilla, and we have found an average of 1.4 axillary sentinel nodes in these patients. Surgical biopsy of the axillary sentinel nodes accurately staged the node field in 96% of patients. We have also found, however, that the pattern of lymphatic drainage from the cancer site is unpredictable; and in 49% of patients lymphatic drainage occurred across the center line of the breast to axillary or internal mammary sentinel nodes. In more than half of our patients (56%) lymphatic drainage occurred to lymph nodes outside the axilla including the internal mammary (45%), supraclavicular (13%), and interpectoral and intramammary interval nodes (12%). These nodes are also sentinel nodes, and their presence indicates that a sentinel node biopsy procedure that stages only the status of the axillary lymph nodes has the potential to understage about half the patients with breast cancer. High quality lymphoscintigraphy allows accurate mapping of peritumoral lymphatic drainage in most patients with breast cancer. It is possible that in the future accurate nodal staging in each individual will involve biopsy of all sentinel lymph nodes, regardless of their location.

Sentinel lymph node biopsy in patients with melanoma and breast cancer.

Sentinel lymph node biopsy (SNLB) is a new method for staging regional node fields in patients with cancers that have a propensity to metastasise to lymph nodes. The majority of early experience has been obtained in patients with melanoma and breast cancer. The technique requires the close cooperation of nuclear medicine physicians, surgical oncologists and histopathologists to achieve the desired accuracy. It involves: (i) identification of all lymph nodes that directly drain a primary tumour site (the sentinel nodes) by the use of pre-operative lymphoscintigraphy, (ii) selective excision of these nodes by the surgeon, guided by pre-operative blue dye injection and a gamma detecting probe intra-operatively and (iii) careful histological examination of the sentinel nodes by the histopathologist using serial sections and immunohistochemical stains. If the nodes are normal it can be inferred with a high degree of accuracy that all nodes in the node field are normal. This means that radical dissections of draining node fields can be avoided in patients with normal lymph nodes. A further advantage of lyamphatic mapping is that drainage to sentinel nodes in unusual locations is identified, leading to more accurate nodal staging than could be achieved with routine dissection of the closest node field.

Lymphatic mapping and sentinel node biopsy for melanoma.

Worldwide experience has now confirmed that the histological status of sentinel nodes (SNs) accurately reflects the status of regional lymph nodes in patients with melanoma. Preoperative lymphoscintigraphy has proved to be invaluable in identifying SNs and in demonstrating unusual lymphatic drainage pathways. Greatest accuracy at the time of surgery is achieved using both blue dye injection and a gamma-probe. Close cooperation between surgeons, nuclear medicine physicians and pathologists is required if the SN biopsy technique is to be reliable. The results of clinical trials will demonstrate whether SN biopsy has any therapeutic value. It is already clear, however, that SN examination provides very accurate staging, and SN biopsy is therefore essential for all melanoma patients entering adjuvant therapy trials.

Reliability of DMSA for the diagnosis of renal parenchymal abnormality in children.

The objective of this study was to evaluate the variability of technetium-99m dimercaptosuccinic acid (DMSA) scintigraphy interpretation by four nuclear medicine physicians for the diagnosis of renal parenchymal abnormality in children, and to compare variability among three different DMSA methods in clinical use: planar alone, single-photon emission tomography (SPET) alone, and planar with SPET. One hundred consecutive DMSA studies were independently interpreted 3 times by four participating nuclear medicine specialists from different departments and in random order. All scans were classified by the presence or absence of renal parenchymal abnormality using the modified four-level grading system of Goldraich. Indices of agreement were the percentage of agreement and the kappa statistic. Disagreement was analysed using children, kidneys and kidney zones (three zones per kidney). Using patients as the unit of analysis, agreement for planar and planar with SPET methods was 87%-88% (kappa 0.74) for the normal-abnormal scan classification. The corresponding agreement value for the SPET alone method was 78% (kappa 0.56). Similarly, substantial disagreement (disagreement > or = 2 categories) occurred in 2.5% and 1.3% of comparisons between observers for planar alone and planar with SPET, respectively, but in 5.2% of comparisons for SPET alone. These results did not vary appreciably whether interpretation of patients, kidneys or kidney zones was compared. It is concluded that the four experienced nuclear medicine physicians showed substantial agreement in the interpretation of planar alone and planar with SPET DMSA scintigraphic images. Interpretation of SPET DMSA images, without planar images, was significantly more variable than interpretation using the two other methods, disagreement occurring in more than 20% of comparisons. SPET DMSA scintigraphy, when used without planar images, does not provide a firm basis for clinical decision making in the care of children who may have renal damage. There is no apparent benefit of reduced variability from the extra provision of SPET data to nuclear medicine physicians who already have planar images.

Interval nodes: the forgotten sentinel nodes in patients with melanoma.

BACKGROUND: Any sentinel lymph node that receives lymph drainage directly from a primary melanoma site, regardless of its location, may contain metastatic disease. This is true even if the sentinel node does not lie in a recognized node field. Interval (in-transit) nodes that lie along the course of a lymphatic vessel between a primary melanoma site and a recognized node field are sometimes seen during lymphatic mapping for sentinel node biopsy. If drainage to such interval nodes is ignored by the surgeon during sentinel node biopsy, metastatic melanoma will be missed in some patients. HYPOTHESIS: When lymph drains directly from a cutaneous melanoma site to an interval node, that sentinel node has the same chance of harboring micrometastatic disease as a sentinel node in a recognized node field. DESIGN: Preoperative lymphoscintigraphy with technetiumTc 99m antimony trisulfide colloid was performed to define lymphatic drainage patterns and, since 1992, to locate the sentinel lymph nodes for surgical biopsy or for permanent skin marking of their location with point tattoos. SETTING: Melanoma unit of a university teaching hospital. PATIENTS: A total of 2045 patients with cutaneous melanoma were studied in 13 years. RESULTS: Interval nodes were found in 148 patients (7.2%). The incidence of interval nodes varied with the site of the primary melanoma. Interval nodes were more common with melanomas on the trunk than with those on the lower limbs. Micrometastatic disease was found in 14% of interval nodes that underwent biopsy as sentinel nodes. This incidence is similar to that found in sentinel nodes located in recognized node fields, confirming the potential clinical importance of interval nodes. CONCLUSIONS: Interval nodes should be removed surgically along with any additional sentinel nodes in standard node fields if the sentinel node biopsy procedure is to be complete. In some patients, an interval node will be the only lymph node that contains metastatic disease.

Role of ischemia and infarction in late right ventricular dysfunction after atrial repair of transposition of the great arteries.

OBJECTIVES: This study was conducted to assess whether myocardial ischemia and/or infarction are involved in the pathogenesis of late right ventricular dysfunction in adult survivors of atrial baffle repair for transposition of the great arteries in infancy. BACKGROUND: The medium-term success of intraatrial baffle repair for transposition of the great arteries is good, with many patients surviving into adult life, but prognosis can be limited by progressive right ventricular dysfunction. We hypothesized that ongoing myocardial ischemia and/or infarction are important factors in the pathogenesis of this complication. Radionuclide techniques offer an opportunity to study both myocardial perfusion and concomitant ventricular wall motion. METHODS: Dipyridamole sestamibi single-photon emission computed tomography followed by rest sestamibi single-photon emission computed tomography was used to assess right ventricular myocardial perfusion, wall motion, wall thickening and ejection fraction in 22 adolescents/young adults who had undergone atrial baffle repair for simple transposition of the great arteries at median 6.7 (range 0.5 to 54) months of age. The patients were aged 10 to 25 (median 15.5) years; 19 in New York Heart Association class I, 2 in class II and 1 in class III. All were in a regular cardiac rhythm during the studies. The right ventricular tomographic images were examined in three parallel and two orthogonal planes, analyzed in 12 segments. RESULTS: Perfusion defects were evident in all patients in at least one segment, in either the rest or stress images. Twelve patients (55%) demonstrated fixed defects only, nine (41%) had fixed and reversible defects and one (4.5%) had reversible defects only. Concomitant wall-thickening abnormalities occurred in 83% of segments with fixed perfusion defects, mirrored by a reduction in wall motion in 91% of segments analyzed. Right ventricular ejection fraction was correlated with age (R = 0.62; p = 0.002), and with wall-thickening abnormalities (R = 0.60; p < 0.005). CONCLUSIONS: Reversible and fixed perfusion defects with concordant regional wall motion abnormalities occur in the right (systemic) ventricle 10 to 20 years after Mustard repair for transposition of the great arteries; this may be important in the pathogenesis of late right ventricular dysfunction in this group.