A pilot study of dual-isotope lymphoscintigraphy for breast sentinel node biopsy comparing intradermal and intraparenchymal injection.

AIMS: Identification of sentinel lymph nodes (SLN) may depend on the tissue plane of tracer injection. To explore this, we developed a dual-isotope technique to compare the lymphatic drainage basins accessed by intradermal and parenchymal injections. METHODS: Fifteen breast cancer patients had simultaneous parenchymal and intradermal injections of (99m)Tc-labelled human immunoglobulin G (HIG) and (111)In-HIG, respectively, 2-4h before axillary lymph node clearance surgery. All 228 freshly dissected nodes were assayed by well counting and examined for metastatic disease by haematoxylin/eosin staining and immuno-histochemistry. RESULTS: Total nodal uptake following intradermal injection was 10 times more than after parenchymal injection. Tracer uptake within the first three draining nodes divided patients into three groups; four (group 1) had identical 1st, 2nd and 3rd echelon nodes, six (group 2) had identical 1st and 2nd echelon nodes and five (group 3) had different 1st echelon nodes. With respect to the first, second and third groups, there was close, moderate and poor correlation (Pearson), respectively, between individual nodal counts accumulated from the two injection sites. Of eight patients with nodal disease, the SLN identified by intradermal and parenchymal injections contained disease in seven and four patients, respectively. CONCLUSIONS: Comparison of nodal tracer distributions from the two injection planes allows a functional model to be developed with two possible routes of drainage from the parenchymal plane, one joining the tract from the areolar plexus and the other passing independently to the axilla which builds upon Sappey's original anatomical model. This may explain the variable uptake, discordance and false negative SLN identification.

Lymphatic transfer studies with immunoglobulin scintigraphy after axillary surgery.

AIMS: The study objective was to investigate the effects of axillary lymph node clearance surgery on the function and morphology of the lymphatic system of the upper limb in women with breast cancer. METHODS: Nineteen women were studied before and 3 months after surgery. Fifteen were studied again 12 months after surgery. On each occasion, scintigraphy following intradermal hand webspace injection of Tc-99m-human polyclonal immunoglobulin was performed to include the affected upper limb and torso. RESULTS: There was considerable functional variability in response to surgery. Seven patients subsequently developed breast cancer-related lymphedema (BCRL). Neither lymph re-routing (defined as a change in lymph vessel morphology or definition) nor linear velocity of protein transit up the arm was associated with the development of BCRL. Blood pool activity, judged from visual inspection of the cardiac blood pool on the whole body images, was earlier and more marked 3 and 12 months after surgery than before. The count rate (per 100 pixels/MBq injected activity), measured in a cardiac region of interest, was significantly higher after surgery than before, was higher in patients who developed BCRL and, in the patient population as a whole, correlated positively with arm swelling. CONCLUSION: The consequences of axillary lymph node clearance were variable, unexpected and largely persistent. An increased rate of access of intradermally injected protein into the blood pool is significantly associated with BCRL.

Variation in lymphatic function may predispose to development of breast cancer-related lymphoedema.

AIMS: Breast cancer-related lymphoedema (BCRL) remains a common complication of breast cancer treatment. Many features of this condition remain poorly understood, such as why only approximately 25% of women are affected after similar treatment, and the phenomenon of 'sparing', in which regions of an otherwise swollen arm, most commonly the hand, remain unaffected. This study uses dual-isotope lymphoscintigraphy, involving measurement of rate of clearance of radiolabelled protein from a subcutaneous depot and subsequent appearance in blood, to quantify alterations in lymphatic function in women with BCRL, and to further investigate differences between those in whom the hand is involved with swelling and those in whom it is spared. METHODS: Participants received a depot injection of human immunoglobulin G in the dorsum of both hands, labeled with technetium-99m on one side and indium-111 on the other. Rates of clearance from the depot and appearance in venous blood were measured at regular intervals over a 3 h period. RESULTS: A total of 18 women with a history of BCRL were studied. Significant reductions in both depot clearance and venous appearance were observed in the affected arm compared with the unaffected contralateral control. On sub-group analysis, significant differences were also observed between swollen and spared hand groups, both for the affected and unaffected contralateral arm. DISCUSSION: This study, as well as confirming impaired lymphatic function in arms affected by BCRL, also shows underlying variation in lymphatic function in the unaffected contralateral arm, between those with and without hand sparing. This raises the possibility that the risk of developing BCRL may be, in part, pre-determined.

Tissue-to-blood transport of radiolabelled immunoglobulin injected into the web spaces of the hands of normal subjects and patients with breast cancer-related lymphoedema.

AIM: The ability to return interstitial protein to central blood is key to the defence against oedema. The aim of this study was to quantify this ability by measuring the rate at which radiolabelled human immunoglobulin (HIgG) accumulated in blood following injection into the subcutis of the hand in normal volunteers and in patients with breast cancer-related lymphoedema (BCRL). METHODS: A total of 37 control subjects (healthy normal volunteers or breast cancer patients prior to treatment) and 18 women with BCRL were studied with dual-isotope lymphoscintigraphy. Each received bilateral subcutaneous depot injection in the dorsal web space of HIgG labelled with Tc-99m on one side and In-111 on the other. Activities remaining at the depot and accumulating in blood were measured at regular intervals for 3 h. Clearance from the depot was exponential and expressed as the rate constant k(depot) (min(-1)). Accumulation in blood was essentially linear and, using an estimate of blood volume based on height and weight, was expressed as the linear constant b(blood) (% administered activity x min(-1)). The time axis intercept of this linear fit was recorded as an index of the minimum time to arrival of radioprotein in blood. The efficiency with which radioprotein that has left the depot (extra-depot activity) is transported into blood [tissue-to-blood (T-B) transport] was quantified (1) as the quotient b(blood)/k(depot), and (2) as a function of time after injection by comparing the total amount of radioprotein in blood at any time with the total amount of radioprotein that was no longer in the depot at the same time. RESULTS: Tc-99m-HIgG and In-111-HIgG behaved similarly and are interchangeable. At all times between 60 and 180 min in controls, about 50% of protein that had left the depot was present in blood. T-B transport was reduced to about 20% in BCRL arms in which the hand was involved in swelling (p < 0.001 versus controls), but remained unchanged in patients in whom the hand was spared. The minimum time to arrival of radioprotein in blood was not reduced in BCRL; on the contrary, there appeared to be a small proportion of injected activity that arrived rapidly in blood in BCRL patients but not in controls. CONCLUSION: We conclude that T-B transport is only impaired in BCRL when radioprotein is injected into swollen tissue. Significant quantities of radioprotein may escape from the arm via local access to blood. Individual variation in this capacity may explain the regional sparing observed in BCRL.