Adjuvant taxanes and the development of breast cancer-related arm lymphoedema.

BACKGROUND: Despite affecting approximately one-quarter of all patients undergoing axillary lymph node dissection, the pathophysiology of breast cancer-related lymphoedema (BCRL) remains poorly understood. More extensive locoregional treatment and higher body mass index have long been identified as major risk factors. This study aimed to identify risk factors for BCRL with a specific focus on the potential impact of chemotherapy on the risk of BCRL. METHODS: This was a retrospective analysis of a cohort of consecutive patients with breast cancer treated at a major London regional teaching hospital between 1 January 2010 and 31 December 2012. All patients had node-positive disease and underwent axillary lymph node dissection. Data regarding tumour-, patient- and treatment-related characteristics were collected prospectively. The diagnosis of BCRL was based on both subjective and objective criteria. Multivariable Cox proportional hazards regression was used to assess the association between treatment and risk of BCRL. RESULTS: Some 27.1 per cent of all patients (74 of 273) developed BCRL over the study period. Administration of taxanes showed a strong association with the development of BCRL, as 52 (33.5 per cent) of 155 patients who received taxanes developed BCRL. Multivariable Cox regression analysis demonstrated that patients who received taxanes were nearly three times more likely to develop BCRL than patients who had no chemotherapy (hazard ratio 2.82, 95 per cent c.i. 1.31 to 6.06). No such increase was observed when taxanes were administered in the neoadjuvant setting. CONCLUSION: The present findings suggest that adjuvant taxanes play a key role in the development of BCRL after surgery. This may support the use of taxanes in a neoadjuvant rather than adjuvant setting.

Global abnormalities in lymphatic function following systemic therapy in patients with breast cancer.

BACKGROUND: Breast cancer-related lymphoedema (BCRL) is a result of interaction between several pathophysiological processes, and is not simply a 'stopcock' effect resulting from removal of axillary lymph nodes. The aim of this study was to test the hypothesis that there is a constitutional 'global' lymphatic dysfunction in patients who develop BCRL. METHODS: Lower-limb lymphoscintigraphy was performed in 30 women who had undergone axillary lymph node dissection at least 3 years previously, of whom 15 had BCRL and 15 did not. No patient had any clinical abnormality of the lower limb. The control group comprised 24 women with no history of cancer or lower-limb lymphoedema. (99m) Tc-Nanocoll was injected subcutaneously into the first webspace of each foot, followed by whole-body imaging. Scans were reported as abnormal if there was delay in lymph transport or rerouting through skin or deep system. Quantification was expressed as the percentage injected activity accumulating in ilioinguinal nodes. RESULTS: Mean(s.d.) ilioinguinal nodal accumulation at 150 min was significantly lower in women with BCRL than in those without (2·7(2·5) versus 5·9(4·8) per cent respectively; P = 0·006). Abnormal findings on lower-limb lymphoscintigraphy were observed in 17 of the 30 patients: ten of the 15 women who had BCRL and seven of the 15 who did not. None of the 24 control subjects had abnormal scan findings. CONCLUSION: Women with BCRL had reduced lower-limb lymph drainage, supporting the hypothesis of a predisposition to BCRL. A surprisingly high proportion of patients with breast cancer also demonstrated lymphatic dysfunction, despite clinically normal lower limbs. Possible explanations could be a systemic effect of breast cancer or its treatment, or an unidentified association between breast cancer and lymphatic dysfunction. REGISTRATION NUMBER: ISRCTN84866416 ( http://www.isrctn.com).

An investigation of lymphovenous communications in the upper limbs of breast cancer patients.

BACKGROUND: Approximately 25% of breast cancer patients who undergo treatment to the axilla develop breast cancer-related lymphoedema (BCRL). The aim of this study was to test the hypothesis that lymphovenous communications (LVCs) open and act as a protective mechanism against the development of BCRL. METHODS: Five patients (Group 1) received intradermal injections of (99m)Technetium-labelled autologous erythrocytes into the 2nd ipsilateral hand webspace before and 6-12 weeks following axillary node clearance surgery (ANC). Ten patients at least three years after ANC were also recruited (Group 2); seven had developed BCRL and three had not. Blood was sampled from ipsilateral and contralateral antecubital veins 5, 15, 30, 60, 120 and 180 min post-injection to assess pre-nodal shunting from lymph to blood (LVCs), since nodes block erythrocyte transit. The proportion of activity remaining in the depot was used to calculate the degree of shunting in those with evidence of LVCs. RESULTS: Significant erythrocyte-bound activity, increasing over time, was detected contralaterally in 3 of the 5 patients from Group 1 (none of whom developed BCRL) and 3 of 7 patients with BCRL from Group 2, which indicated the presence of LVCs. The degree of shunting was more marked in those patients who did not develop BCRL compared with those who did. CONCLUSIONS: The time-course of erythrocyte-bound contralateral activity indicates transit through lymphovenous communications rather than needle-induced trauma. Lymphovenous communications large enough to transmit erythrocytes are probably constitutional rather than induced. A larger study is warranted to assess any resulting protection against BCRL.

A constitutional predisposition to breast cancer-related lymphoedema and effect of axillary lymph node surgery on forearm muscle lymph flow.

AIM: The aims of this prospective study were (a) to examine the relationship between pre-operative muscle lymph flow and the predisposition to BCRL in women treated by axillary nodal surgery for breast cancer; and (b) to test the 'stopcock' hypothesis that axillary lymph node surgery impairs forearm lymph flow in the short term. METHODS: (99m)Tc-nanocoll was injected intramuscularly into both forearms of women undergoing surgery for breast cancer. Lymphatic clearance rate constant, k, representing lymph flow per unit interstitial fluid volume, was measured as the fractional disappearance rate of radioactivity from the depot site by gamma camera imaging. Axillary lymph node activity was calculated as percentage injected activity. BCRL was assessed by clinical examination and upper limb perometry. RESULTS: Of 38 pre-operative women, 33 attended at 8 ± 6 weeks post-operatively and 31 at 58 ± 9 weeks post-operatively. Seven patients (18%) developed BCRL. Prior to surgery the BCRL-destined patients had a higher mean k (0.0962 ± 0.034%/min) than non-BCRL patients (0.0830 ± 0.019%/min) (p = 0.10, unpaired t test). Post-operative k values were not significantly different from pre-operative, in either the ipsilateral (operated) or contralateral limb. Also, post-operative k values did not differ significantly between both upper limbs. Furthermore, there was no significant difference between pre- and post-operative axillary activity. CONCLUSION: Patients who develop BCRL have high lymph flow pre-surgery, which may predispose them to lymphatic overload and failure. Axillary lymph node surgery has no early, measurable effect on forearm muscle lymph flow despite surgical disruption of routes of lymph drainage.

Imaging of multidrug resistance in cancer.

Primary intrinsic and/or acquired multidrug resistance (MDR) is the main obstacle to successful cancer treatment. Functional molecular imaging of MDR in cancer using single photon or positron emitters may be helpful to identify multidrug-resistant tumours and predict not only those patients who are resistant to treatment, with a clinically unfavourable prognosis, but also those who are susceptible to the development of drug toxicity or even certain tumours . Variations in the mdr1 gene product may directly affect the therapeutic effectiveness, and single nucleotide polymorphisms for the mdr1 gene may be associated with altered oral bioavailability of MDR1 substrates, drug resistance, and a susceptibility to some human diseases. The challenge of translating the concept of MDR modulation in vivo involves a complex cellular interplay between both malignant and normal cells. Integration and correlation of functional single photon emission tomography or positron emission tomography imaging findings with mdr1 genotype and clinical data may contribute to efficient management by selecting cancer patients with the appropriate molecular phenotype for maximal individual therapeutic benefit, as well as those who are non-responders. This review describes a role for functional imaging of classical mechanisms of MDR with an emphasis on readily available [(99m)Tc]MIBI scintigraphy. MIBI scintigraphy has been shown to be a non-invasive cost-effective in vivo assay of ATP-binding cassette transporters associated with MDR in cancer, including P-glycoprotein, multidrug-resistant protein 1 and breast cancer resistant protein. New imaging agents for molecular targets such as vascular endothelial growth factor and HER2 receptors, may potentially be combined with MDR imaging substrates to more accurately predict the therapeutic response to anticancer drugs, guiding individualised treatment while minimising the economic health costs of ineffective therapy in an era of personalised medicine.

Sympathetic nerve damage as a potential cause of lymphoedema after axillary dissection for breast cancer.

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSION: Lymphoedema is not the result of sympathetic nerve damage sustained during ALND. Preoperative FVR may help predict who will get lymphoedema following this surgery.

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.

Human lymphatic pumping measured in healthy and lymphoedematous arms by lymphatic congestion lymphoscintigraphy.

Axillary surgery for breast cancer partially obstructs lymph outflow from the arm, chronically raising the lymphatic smooth muscle afterload. This may lead to pump failure, as in hypertensive cardiac failure, and could explain features of breast cancer treatment-related lymphoedema (BCRL) such as its delayed onset. A new method was developed to measure human lymphatic contractility non-invasively and test the hypothesis of contractile impairment. 99mTc-human IgG (Tc-HIG), injected into the hand dermis, drained into the arm lymphatic system which was imaged using a gamma-camera. Lymph transit time from hand to axilla, ttransit, was 9.6+/-7.2 min (mean+/-s.d.) (velocity 8.9 cm min(-1)) in seven normal subjects. To assess lymphatic contractility, a sphygmomanometer cuff around the upper arm was inflated to 60 mmHg (Pcuff) before 99mTc-HIG injection and maintained for>>ttransit. When Pcuff exceeded the maximum pressure generated by the lymphatic pump (Ppump), radiolabelled lymph was held up at the distal cuff border. Pcuff was then lowered in 10 mmHg steps until 99mTc-HIG began to flow under the cuff to the axilla, indicating Ppump>or=Pcuff. In 16 normal subjects Ppump was 39+/-14 mmHg. Ppump was 38% lower in 16 women with BCRL, namely 24+/-19 mmHg (P=0.014, Student's unpaired t test), and correlated negatively with the degree of swelling (12-56%). Blood radiolabel accumulation proved an unreliable measure of lymphatic pump function. Lymphatic congestion lymphoscintigraphy thus provided a quantitative measure of human lymphatic contractility without surgical cut-down, and the results supported the hypothesis of lymphatic pump failure in BCRL.

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.

Pyoderma gangraenosum, a rare, but potentially fatal complication in paediatric oncology patients.

Pyoderma gangraenosum (PG) is a serious chronic, ulcerative skin disorder afflicting both adults and children. As PG is often associated with systemic diseases (>50%) such as inflammatory bowel disease, rheumatoid arthritis or haematological disorders, it requires a multidisciplinary approach. This disorder is not commonly reported in paediatrics; therefore children with PG represent a particularly difficult diagnostic challenge. Clinical diagnosis is often delayed and PG is only considered after eliminating other causes of cutaneous ulcers. We report a 4-year-old boy with secondary myelodysplastic syndrome following treatment for acute lymphoblastic leukaemia who presented with a massive inflammatory, ulcerative proliferation of the lower lip which was diagnosed as PG. We have reviewed the literature with reference to diagnostic criteria and treatment options of this disorder that is particularly rare in childhood.

Maternal hemoglobin concentration during pregnancy and risk of infant leukaemia: a children's oncology group study.

In contrast to the positive association found in three studies between maternal anaemia during pregnancy and childhood leukaemia, no such association was found in infant leukaemia (odds ratio 0.85, 95% confidence interval 0.53-1.37).

Radioguided occult lesion localisation (ROLL) and sentinel node biopsy for impalpable invasive breast cancer.

AIM: The aim of this study was to simplify the technique of ROLL and sentinel node biopsy without compromising tumour excision and sentinel node biopsy. METHODS: 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. RESULTS: 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. CONCLUSIONS: This modification of the previously described ROLL technique is feasible and safe and does not compromise tumour excision or sentinel node detection.

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.

Impairment of lymph drainage in subfascial compartment of forearm in breast cancer-related lymphedema.

BACKGROUND: In arm lymphedema secondary to axillary surgery and radiotherapy (breast cancer-related lymphedema), the swelling is largely epifascial and lymph flow per unit epifascial volume is impaired. The subfascial muscle compartment is not measurably swollen despite the iatrogenic damage to its axillary drainage pathway, but this could be due to its low compliance. Our aim was to test the hypothesis that subfascial lymph drainage too is impaired. METHODS AND RESULTS: Quantitative lymphoscintigraphy was used to measure the removal rate constant (local lymph flow per unit distribution volume) for technetium-99m-human immunoglobulin G injected intramuscularly in the forearms of nine women with unilateral lymphedema. The removal rate constant was on average 31% lower in the ipsilateral swollen forearm than in the contralateral forearm (swollen arm: -0.096+/-0.041% min(-1), contralateral arm: -0.138+/-0.037% min(-1); mean+/-SD, p = 0.037). The decrease in subfascial rate constant correlated strongly with increase in arm volume (r = -0.88, p = 0.002), even though the swelling is mainly epifascial. There was no convincing evidence of dermal backflow. CONCLUSIONS: Lymph flow in the subfascial muscle compartment is decreased in breast cancer-related lymphedema. The correlation between impairment of subfascial drainage and epifascial arm swelling could be because both depend on the severity of axillary damage, or because loss of function in subfascial lymphatics impairs drainage from the epifascial to the subfascial system.

Polyethylene glycol in the design of tumor-targetting radiolabelled macromolecules -- lessons from liposomes and monoclonal antibodies.

Radiolabelled macromolecules such as liposomes and monoclonal antibodies (Mab) are attractive agents for tumour-targetting studies. In addition to their potential diagnostic role, they can also provide vital information on the targetting capacity of therapeutic agents. Certainly in the case of liposome development, this ability to track the pharmacokinetics and biodistribution of the agents in a non-invasive fashion has assisted the design and application of therapeutic liposomal agents. A significant limitation of unmodified liposomes and Mab is their tendency to be cleared rapidly from the circulation. The use of polyethylene glycol (PEG) in the formulation of these agents has the capacity to alter their biological behaviour in such a way as to improve their ability to target tumours. In this paper we review the data relating to the use of PEG-modified liposomes and Mab in the context of nuclear medicine studies.

Phase II study of pegylated liposomal doxorubicin (Caelyx) as induction chemotherapy for patients with squamous cell cancer of the head and neck.

A phase II trial of pegylated liposomal doxorubicin (Caelyx) as induction chemotherapy was conducted in 20 patients with treatment-naïve squamous cell cancer of the head and neck (SCCHN). 10 patients received two cycles of Caelyx (40 mg/m(2)) every 3 weeks before starting radical radiotherapy (RT). Subsequently, consecutive groups of 3 patients received a third escalating dose of Caelyx (10, 15 and 20 mg/m(2)) 3 days before RT. 9 of 18 (50%, 95% confidence intervals (CI): 26-74%) evaluable patients responded to Caelyx, with 11 responses in 26 (42%, 95% CI: 24-62%) evaluable sites (three complete responses (12%), eight partial responses (31%)). There was no grade 3/4 haematological, mucosal or cardiac toxicity. Nausea and vomiting were minimal. There were no drug-related RT delays. Local RT-induced toxicity was not increased. Caelyx has significant activity against SCCHN and warrants further investigation in this disease. In view of its tumour targeting properties and activity at moderate doses, it may be useful in concomitant chemoradiotherapy strategies for SCCHN.

Detection of pelvic lymph node metastases in gynecologic malignancy: a comparison of CT, MR imaging, and positron emission tomography.

OBJECTIVE: Accurate assessment of lymph node status before treatment is critical in the treatment of gynecologic cancers because the 5-year survival and treatment of women is influenced by lymph node involvement. The aims of this study were to investigate the ability of X-ray CT, MR imaging, and (18)F-FDG positron emission tomography (PET) to detect pelvic lymph node metastases by comparing imaging with histopathologic findings after lymph node dissection. MATERIALS AND METHODS: Eighteen patients with gynecologic cancers were studied by all three imaging methods before surgery. The images were initially reviewed with routine diagnostic conditions and then, subsequently, by two observers who were unaware of the clinical and histopathologic findings of the patients. The nodal sites were split into upper (aortic to common iliac bifurcations) and lower (common iliac bifurcations to inguinal ligament) iliac chains. All observers' results were statistically analyzed with specificity, sensitivity, positive and negative predictive values, Fisher's exact test (individual observers) or chi-square test (combined observers), and Cohen's kappa test. RESULTS: Eight of 18 patients had lymph node metastases at histology. Findings of all three modalities agreed in full in only one patient. CT correctly revealed 10 node-negative patients, whereas MR imaging was correct in eight of these patients. (18)F-FDG PET correctly depicted one patient with lymph nodes negative for tumor. CT was the most specific imaging modality (97.0%), with MR imaging and PET rendering values of 90.7% and 77.3%, respectively, but sensitivity of all modalities was low (CT, 48.1%; MR imaging, 53.7%; PET, 24.5%). Observer agreement for each modality was good; kappa values among all observers were 0.88 for CT, 0.85 for MR imaging, and 0.72 for PET. CONCLUSION: CT is the most specific modality for detecting lymph nodes positive for tumor in gynecologic cancers, whereas MR imaging is the most sensitive. The poor results of PET in the pelvis are attributed to urinary (18)F-FDG in the ureters or bladder, which may mask or imitate lymph node metastases.

Differences in lymph drainage between swollen and non-swollen regions in arms with breast-cancer-related lymphoedema.

Recent research indicates that the pathophysiology of breast-cancer-related lymphoedema (BCRL) is more complex than simple axillary lymphatic obstruction as a result of the cancer treatment. Uneven distribution of swelling (involvement of the mid-arm region is common, but the hand is often spared) is puzzling. Our aim was to test the hypothesis that local differences in lymphatic drainage contribute to the regionality of the oedema. Using lymphoscintigraphy, we measured the removal rate constant, k (representing local lymph flow per unit distribution volume, VD), for 99mTc-labelled human immunoglobulin G in the oedematous proximal forearm, and in the hand (finger web) in women in whom the hand was unaffected. Tracer was injected subcutaneously, and the depot plus the rest of the arm was monitored with a gamma-radiation camera for up to 6 h. VD was assessed from image width. Contralateral arms served as controls. k was 25% lower in oedematous forearm tissue than in the control arm (BCRL, -0.070+/-0.026% x min(-1); control, -0.093+/-0.028% x min(-1); mean+/-S.D.; P=0.012) and VD was greater. In the non-oedematous hand of the BCRL arm, k was 18% higher than in the control hand (BCRL, -0.110+/-0.027% x min(-1); control, -0.095+/-0.028% x min(-1); P=0.057) and 59% higher than forearm k on the BCRL side (P=0.0014). VD did not differ between the hands. Images of the BCRL arm following hand injection showed diffuse activity in the superficial tissues, sometimes extending almost to the shoulder. A possible interpretation is that the hand is spared in some patients because local lymph flow is increased and diverted along collateral dermal routes. The results support the hypothesis that regional differences in surviving lymphatic function contribute to the distribution of swelling.