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ABSTRACT: The physiological disturbances leading to lymphoedema after breast cancer surgery are poorly understood. Damage to sympathetic nerves during axillary lymph node dissection (ALND), leading to increased capillary fluid filtration, was investigated as a possible contributory factor.
The integrity of the upper limb sympathetic nervous system was tested in 36 patients before, and 3 and 12 months after ALND. Forearm vascular resistance (FVR), calculated from forearm blood flow and mean systemic arterial pressure, was measured before and after exposure to lower-body negative pressure. Forearm venous compliance was measured using (99m)Tc-labelled autologous erythrocytes and radionuclide plethysmography before and after cold water immersion of the feet.
There were clear changes in FVR and venous compliance in response to sympathetic stimulation but no differences attributable to surgery or between the nine patients who developed lymphoedema and the 27 who did not; nor were there differences between the two arms. There was a trend towards lower preoperative FVR in patients who developed lymphoedema.
Lymphoedema is not the result of sympathetic nerve damage sustained during ALND. Preoperative FVR may help predict who will get lymphoedema following this surgery.
British Journal of Surgery 09/2009; 96(8):865-9. · 4.61 Impact Factor
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J C Fowler,
C K Solanki,
I Guenther,
R Barber,
F Miller,
L Bobrow,
D Ravichandran,
D Lawrence,
J R Ballinger,
A Douglas-Jones,
A D Purushotham, A M Peters
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ABSTRACT: 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.
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.
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.
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.
European journal of surgical oncology: the journal of the European Society of Surgical Oncology and the British Association of Surgical Oncology 05/2009; 35(10):1041-7. · 2.56 Impact Factor
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ABSTRACT: 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.
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.
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.
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.
European journal of surgical oncology: the journal of the European Society of Surgical Oncology and the British Association of Surgical Oncology 12/2007; 33(9):1052-60. · 2.56 Impact Factor
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ABSTRACT: As iodinated contrast medium is cleared by glomerular filtration, it should be possible to apply the same principles utilized in radionuclide studies to derive differential renal function by comparison of enhancing renal volumes derived from contrast enhanced multidetector CT (CEMDCT). Having established a technique iteratively which appeared successful, a retrospective study was performed using 25 consecutive patients with a wide range of urological conditions who had undergone both CEMDCT, including the renal area in the portal venous phase, and nuclear medicine (NM) assessment of renal function with no urological intervention between the studies. Proprietary volume software was used to quantify the volume and attenuation of each kidney, the products of which (after subtraction of soft tissue attenuation derived from a region of interest over psoas) gave right and left enhancing renal volumes. The contribution by each kidney as a percentage of total renal enhancing tissue was derived. Comparison with NM studies resulted in excellent correlation of relative renal function by CEMDCT and NM assessments having a regression of near unity and a Pearson's correlation coefficient of 0.96. Bland Altman and Passing Bablock tests confirmed good agreement between the two methods with no bias. This is a simple, practicable processing technique using standard portal venous phase CEMDCT images to quantify differential function. This technique may allow a one-stop CT assessment of both anatomy and function.
The British journal of radiology 01/2007; 79(948):935-42. · 2.11 Impact Factor
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ABSTRACT: The aim of this study was to simplify the technique of ROLL and sentinel node biopsy without compromising tumour excision and sentinel node biopsy.
Twenty patients with impalpable primary invasive breast carcinoma underwent an injection of 99mTc-nanocolloid mixed with radiographic contrast medium Iohexol into the centre of the lesion under ultrasound or stereotactic guidance pre-operatively. No guidewire localisation was performed. Under general anaesthesia, a periareolar intradermal/subcutaneous injection of patent blue-V dye was performed. The sentinel node was identified by blue-stained lymphatics and node and a hot spot on the gamma probe. Surgical excision of the primary tumour was then carried out using the gamma probe.
In eight of 20 cases an immediate re-excision was carried out and on histological assessment, all 20 patients were clear of invasive disease at the margins. In two patients, in situ disease was present at the margins and a further re-excision was therefore performed. The sentinel node was identified in all cases. In all, five of 20 patients were node positive on routine HE staining. In a further two patients, tumour cells were identified by immunohistochemistry with CAM5.2 antibody. Completion axillary clearance in six patients confirmed that the sentinel node was the only positive node.
This modification of the previously described ROLL technique is feasible and safe and does not compromise tumour excision or sentinel node detection.
European Journal of Surgical Oncology 12/2004; 30(9):918-23. · 2.50 Impact Factor
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C J S Price,
D K Menon, A M Peters,
J R Ballinger,
R W Barber,
K K Balan,
A Lynch,
J H Xuereb,
T Fryer,
J V Guadagno,
E A Warburton
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ABSTRACT: Evidence now exists for a pathogenic role for neutrophils in acute cerebral ischemia. We have studied the patterns and temporal profile of cerebral neutrophil recruitment to areas of acute ischemic stroke (IS) and have attempted to correlate this with neurological status and outcome.
Patients with cortical middle cerebral artery (MCA) IS were recruited within 24 hours of clinical onset. Neutrophil recruitment was studied using indium-111 (111In) troponolate-labeled neutrophils, planar imaging, and single-photon emission computed tomography (SPECT). Volume of brain infarction was calculated from concurrent computed tomography (CT). Hematoxylin and eosin sections were obtained postmortem (n=2). Outcome was measured using Barthel, Rankin, and National Institute of Health Stroke (NIHSS) scales.
Fifteen patients were studied. Significant 111In-neutrophil recruitment to ipsilateral hemisphere, as measured by asymmetry index (AI), was demonstrated within 24 hours of onset in 9 patients; this response was heterogenous between patients and on repeated measurement attenuated over time. Histologically, recruitment was confirmed within intravascular, intramural, and intraparenchymal compartments. Interindividual heterogeneity in neutrophil response did not correlate with infarct volume or outcome. In an exploratory analysis, neutrophil accumulation appeared to correlate significantly with infarct expansion (Spearman rho=0.66; P=0.03, n=12).
Neutrophils recruit to areas of ischemic brain within 24 hours of symptom onset. This recruitment attenuates over time and is confirmed histologically. While neutrophil accumulation may be associated with either the magnitude or the rate of infarct growth, these results require confirmation in future studies.
Stroke 08/2004; 35(7):1659-64. · 5.73 Impact Factor
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ABSTRACT: 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.
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.
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.
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.
European Journal of Surgical Oncology 07/2004; 30(5):508-14. · 2.50 Impact Factor
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ABSTRACT: 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).
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.
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.
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.
Journal of Vascular Research 41(2):183-92. · 2.65 Impact Factor
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ABSTRACT: AimsThe 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.MethodsNineteen 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.ResultsThere 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.ConclusionThe 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.
European Journal of Surgical Oncology (EJSO).
